ALBERT

Description: Organic and organometallic reactants in aqueous electrolytes, being composed of earth-abundant elements, are promising redox active candidates for cost-effective organic redox flow batteries (ORFBs). Various compounds of ferrocene and methyl viologen have been examined as promising redox actives for this application. Herein, we examined the influence of the electrolyte pH and the salt anion on model redox active organic cations, bis((3-trimethylammonio) propyl)- ferrocene dichloride (BTMAP-Fc) and bis(3-trimethylammonio) propyl viologen tetrachloride (BTMAP-Vi), which have exhibited excellent cycling stability and capacity retention at ≥1.00 M concentration [E. S. Beh, et al. ACS Energy Lett. 2, 639–644 (2017)]. We examined the solvation shell around BTMAP-Fc and BTMAP-Vi at acidic and neutral pH with SO42-, Cl−, and CH3SO3− counterions and elucidated their impact on cation diffusion coefficient, first electron transfer rate constant, and thereby the electrochemical Thiele modulus. The electrochemical Thiele modulus was found to be exponentially correlated with the solvent reorganizational energy (λ) in both neutral and acidic pH. Thus, λ is proposed as a universal descriptor and selection criteria for organic redox flow battery electrolyte compositions. In the specific case of the BTMAP-Fc/BTMAP-Vi ORFB, low pH electrolytes with methanesulfonate or chloride counterions were identified as offering the best balance of transport and kinetic requirements.

Description: When displayed on erythrocytes, peptides and proteins can drive antigen-specific immune tolerance. Here, we investigated a straightforward approach based on erythrocyte binding to promote antigen-specific tolerance to both peptides and proteins. We first identified a robust erythrocyte-binding ligand. A pool of one million fully d-chiral peptides was injected into mice, blood cells were isolated, and ligands enriched on these cells were identified using nano-liquid chromatography–tandem mass spectrometry. One round of selection yielded a murine erythrocyte-binding ligand with an 80 nM apparent dissociation constant, Kd. We modified an 83-kDa bacterial protein and a peptide antigen derived from ovalbumin (OVA) with the identified erythrocyte-binding ligand. An administration of the engineered bacterial protein led to decreased protein-specific antibodies in mice. Similarly, mice given the engineered OVA-derived peptide had decreased inflammatory anti-OVA CD8+ T cell responses. These findings suggest that our tolerance-induction strategy is applicable to both peptide and protein antigens and that our in vivo selection strategy can be used for de novo discovery of robust erythrocyte-binding ligands.

Description: Platinum group elements (PGE) are considered to be very poorly soluble in aqueous fluids in most natural hydrothermal–magmatic contexts and industrial processes. Here, we combined in situ X-ray absorption spectroscopy and solubility experiments with atomistic and thermodynamic simulations to demonstrate that the trisulfur radical ion S3•− forms very stable and soluble complexes with both PtII and PtIV in sulfur-bearing aqueous solution at elevated temperatures (∼300 °C). These Pt-bearing species enable (re)mobilization, transfer, and focused precipitation of platinum up to 10,000 times more efficiently than any other common inorganic ligand, such as hydroxide, chloride, sulfate, or sulfide. Our results imply a far more important contribution of sulfur-bearing hydrothermal fluids to PGE transfer and accumulation in the Earth’s crust than believed previously. This discovery challenges traditional models of PGE economic concentration from silicate and sulfide melts and provides new possibilities for resource prospecting in hydrothermal shallow crust settings. The exceptionally high capacity of the S3•− ion to bind platinum may also offer new routes for PGE selective extraction from ore and hydrothermal synthesis of noble metal nanomaterials.

Description: Objectives N-Terminal pro Brain Natriuretic Peptide (NT-proBNP) is a diagnostic marker for heart failure and a prognostic factor for cardiovascular disease (CVD). The aim of this study was to examine the association of socioeconomic position (SEP) with NT-proBNP while assessing sex-differences and the impact of CVD risk factors and prevalent CVD on the association. Methods Baseline data of 4598 participants aged 45–75 years of the Heinz Nixdorf Recall Study were used. Income and education were used as SEP indicators. Age- and sex-adjusted linear regression models were fitted to calculate effect size estimates and 95% confidence intervals (95%-CIs) for the total effect of SEP indicators on NT-proBNP, while potential mediation was assessed by additionally accounting for traditional CVD risk factors (i.e., systolic blood pressure, HDL cholesterol, LDL cholesterol, diabetes, anti-hypertensive medication, lipid-lowering medication, BMI, current smoking). Education and income were included separately in the models. Results With an age- and sex-adjusted average change in NT-proBNP of -6.47% (95%-CI: -9.91; -2.91) per 1000€, the association between income and NT-proBNP was more pronounced compared to using education as a SEP indicator (-0.80% [95%-CI: -1.92; 0.32] per year of education). Sex-stratified results indicated stronger associations in men (-8.43% [95%-CI: -13.21; -3.38] per 1000€; -1.63% [95%-CI: -3.23; -0.001] per year of education) compared to women (-5.10% [95%-CI: -9.82; -0.01] per 1000€; -1.04% [95%-CI: -2.59; 0.50] per year of education). After adjusting for CVD risk factors some of the observed effect size estimates were attenuated, while the overall association between SEP indicators and NT-proBNP was still indicated. The exclusion of participants with prevalent coronary heart disease or stroke did not lead to a substantial change in the observed associations. Conclusions In the present study associations of education and income with NT-proBNP were observed in a population-based study sample. Only parts of the association were explained by traditional CVD risk factors, while there were substantial sex-differences in the strength of the observed association. Overt coronary heart disease or stroke did not seem to trigger the associations.

Description: The maned wolf (Chrysocyon brachyurus) is an induced ovulator. Though the mechanism of ovulation induction remains unknown, it is suspected to be urinary chemical signals excreted by males. This study assessed volatile organic compounds (VOCs) in weekly urine samples across 5 months from 13 maned wolves (6 intact males, 1 neutered male, 6 females) with the goal of identifying VOCs that are differentially expressed across sex, reproductive status, and pairing status. Solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) were used to extract and separate VOCs that were identified via spectral matching with authentic standards, with spectral libraries, or with new software that further matches molecular fragment structures with mass spectral peaks. Two VOCs were present across all 317 urine samples: 2,5-dimethyl pyrazine and 2-methyl-6-(1-propenyl)-pyrazine. Fifteen VOCs differed significantly (Adj. P 〈 0.001 and |log2 fold change| 〉2.0) between intact males and females. Using partial least squares-discriminant analysis, the compounds with the highest importance to the sex classification were delta-decalactone, delta-dodecalactone, and bis(prenyl) sulfide. Sixty-two VOCs differed between intact males and the neutered male. Important classifier compounds were 3-ethyl 2,5-dimethyl pyrazine, 2-methyl-6-(1-propenyl)-pyrazine, and tetrahydro-2-isopentyl-5-propyl furan. Several VOCs established as important here have been implicated in reproductive communication in other mammals. This study is the most robust examination of differential expression in the maned wolf thus far and provides the most comprehensive analysis of maned wolf urinary VOCs to date, increasing the sample size substantially over previous chemical communication studies in this species. New data analysis software allowed for the identification of compounds in the hormone-producing mevalonate pathway which were previously unreported in maned wolf urine. Several putative semiochemicals were identified as good candidates for behavioral bioassays to determine their role in maned wolf reproduction, and specifically in ovulation induction.

Description: COVID-19 might have long-term mental health impacts. We aim to investigate the longitudinal changes in mental problems from initial COVID-19 peak to its aftermath among general public in China. Depression, anxiety and insomnia were assessed among a large-sample nationwide cohort of 10,492 adults during the initial COVID-19 peak (28 February 2020 to 11 March 2020) and its aftermath (8 July 2020 to 8 August 2020) using the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and Insomnia Severity Index. We used generalized estimating equations and linear mixed models to explore factors associated with long-term mental health symptoms during COVID-19. During the five months, mental health symptoms remained consistently elevated (baseline 46.4%; follow-up 45.1%). Long-term depression, anxiety and insomnia were associated with several personal and work-related factors including quarantine (adjusted OR for any mental health symptoms 1.31, 95%CI 1.22–1.41, p 〈 0.001), increases in work burden after resuming work (1.77, 1.65–1.90, p 〈 0.001), occupational exposure risk to COVID-19 (1.26, 1.14–1.40, p 〈 0.001) and living in places severely affected by initial COVID-19 peak (1.21, 1.04–1.41, p = 0.01) or by a COVID-19 resurgence (1.38, 1.26–1.50, p 〈 0.001). Compliance with self-protection measures, such as wearing face masks (0.74, 0.61–0.90, p = 0.003), was associated with lower long-term risk of mental problems. The findings reveal a pronounced and prolonged mental health burden from the initial COVID-19 peak through to its aftermath in China. We should regularly monitor the mental health status of vulnerable populations throughout COVID-19.

Description: Malaysia implemented its first Movement Control Order (MCO) during the early phase of the COVID-19 pandemic to slow the transmission of the virus. This study aimed to explore the public perception of the MCO implementation and people’s experiences during this period. The study employed qualitative explorative in-depth interviews conducted with 23 Malaysian adults from various demographic backgrounds. Thematic analysis was performed using NVivo 12. Three main themes were identified: a period of information surge, heterogeneous emotional response, and attempts to adapt. During the MCO, the participants obtained information from multiple platforms. They suggested the need for clear and repeated instructions to avoid confusion and misinformation. They also acknowledged the importance of the MCO in breaking the chain of transmission and safeguarding high-risk groups; however, they also expressed that stricter enforcement from the authorities was warranted. The changes in the participants’ work–life routines, lack of physical interaction, and uncertainty about their health and the economy due to the MCO negatively impacted their psychological states. Despite these challenges, the participants attempted to adapt to life under the MCO in different ways. The findings imply that during a crisis, the public tends to seek clear and reliable information, experience emotional turmoil, and adapt to changes. The MCO implementation can be improved through an effective communication strategy and efforts to battle misinformation.

Description: The number of medically compromised dental patients is increasing every year with the increase in the super-aged population. Many of these patients have underlying psychiatric problems and diseases, which need to be recognized by dental professionals for better treatment outcomes. The aim of this narrative review article is to summarize the psychological and psychiatric backgrounds of medically compromised patients who are frequently visited and taken care of by dentists using findings from recent systematic reviews and meta-analyses. Anxiety and symptoms of depression, post-traumatic stress disorders, panic disorders, poor cognitive functions, and poor quality of life were some of the common psychological backgrounds in medically compromised patients. Additionally, the consequences of these psychological problems and the considerations that need to be taken by the dentist while treating these patients have been discussed. Dental professionals should be aware of and recognize the different psychological backgrounds of medically compromised dental patients in order to provide appropriate dental treatment and to prevent oral conditions from worsening.

Description: Background Patients admitted to intensive care units (ICU) are at an increased risk of developing immobility related complications. Physiotherapists are challenged to employ preventive and rehabilitative strategies to combat these effects. Passive limb range of motion (PROM) exercises- a part of early mobilization-aid in maintaining joint range of motion and functional muscle strength and forms a part of treatment for patients in ICU. However, there is a lack of evidence on practice of PROM exercises on patients admitted to ICU in the United Arab Emirates (UAE). This study aimed at exploring practices regarding the same in UAE. Methods This survey, conducted from January 2021 to February 2021 in College of Physiotherapy, Sharjah University studied practice of physiotherapists in the intensive care units. Physiotherapists currently working in ICU completed an online questionnaire composed of forty-two questions about physiotherapy service provision, assessment and intervention in the intensive care units. Results 33 physiotherapists completed the survey. 66.6% of respondents routinely assessed PROM for all the patients in ICU referred for physiotherapy. 84.8% of them assessed all the joints. More than half of the respondents (57.8%) reported that they administered PROM regularly to all the patients. According to 63.6% respondents, maintaining joint range of motion was the main reason for performing PROM. Responses pertaining to sets and repetitions of PROM were variable ranging from 1–6 sets and from 3 to 30 repetitions. Personal experience, resources/financial consideration and research findings were found to have influence on the practice. Conclusions PROM was found to be one of the frequently used mobilization techniques administered by physiotherapists in the intensive care units and was mostly performed after assessment. Maintaining joint range of motion was the main aim for performing PROM. Variability was found in the sets and repetitions of PROM administered. Various factors influenced the practice of PROM.

Description: The role the mammary epithelial circadian clock plays in gland development and lactation is unknown. We hypothesized that mammary epithelial clocks function to regulate mammogenesis and lactogenesis, and propose the core clock transcription factor BMAL1:CLOCK regulates genes that control mammary epithelial development and milk synthesis. Our objective was to identify transcriptional targets of BMAL1 in undifferentiated (UNDIFF) and lactogen differentiated (DIFF) mammary epithelial cells (HC11) using ChIP-seq. Ensembl gene IDs with the nearest transcriptional start site to ChIP-seq peaks were explored as potential targets, and represented 846 protein coding genes common to UNDIFF and DIFF cells and 2773 unique to DIFF samples. Genes with overlapping peaks between samples (1343) enriched cell-cell adhesion, membrane transporters and lipid metabolism categories. To functionally verify targets, an HC11 line with Bmal1 gene knocked out (BMAL1-KO) using CRISPR-CAS was created. BMAL1-KO cultures had lower cell densities over an eight-day growth curve, which was associated with increased (p

Description: Objectives N-benzoyl-DL-arginine peptidase (trypsin-like peptidase) is specifically produced by certain strains of periodontitis-associated bacteria. We aimed to examine the effectiveness of an objectively quantified trypsin-like peptidase activity assay (TLP-AA) for detecting severe periodontitis. Methods The study population included 347 adults (108 men and 239 women; average age, 43.3 years) who underwent a full-mouth periodontal examination. Specimens for the TLP-AA were obtained using tongue swabs. Using a color reader, the TLP-AA results were obtained as a* values, with higher positive a* values indicating an increased intense enzymatic activity. The predictive validity of the TLP-AA results for severe periodontitis was assessed using receiver operating characteristic curve analysis and the periodontitis case definition provided by the Centers for Disease Control and Prevention/American Academy of Periodontology as the gold standard. Furthermore, multivariable logistic regression analyses were performed to predict severe periodontitis using the TLP-AA results and health characteristics, as the exposure variables. Results Severe periodontitis was observed in 5.2% of the participants. TLP-AA had high diagnostic accuracy for severe periodontitis, with an area under the curve of 0.83 (95% confidence interval [CI]: 0.75–0.92). The cut-off score for the a* value that best differentiated individuals with severe periodontitis was 0.09, with a sensitivity of 83% and specificity of 77%. Multivariable logistic regression analyses revealed that the TLP-AA results were significantly associated with severe periodontitis after adjusting for health characteristics (adjusted odds ratios: 1.90 [95% CI: 1.37–2.62] for the a* value). Conclusions Objectively quantified TLP-AA results are potentially useful for detecting severe periodontitis in epidemiological surveillance.

Description: Introduction Suicidality is a risk of a person committing suicide often characterized by suicidal ideation, intent or attempts. Despite the high burden of suicidality among individuals living with HIV and HAIDS, there is paucity of data on the impact of suicidality on clinical (such as CD4 counts and HIV disease progression) and behavioural outcomes (such as adherence to HIV Medications). Cross-sectional investigations of these associations are often complicated by bidirectional causal relationships and hence the need for longitudinal study designs. We conducted a cohort study to determine the impact of suicidality on clinical and behavioural outcomes among adults living with HIV/AIDS in Uganda. Materials and methods We conducted the study among 1099 ART naïve adults living with HIV/AIDS in Uganda. Data were collected at three time points: baseline, 6 and 12 months. Multiple regression and discrete time survival models were used to determine the relationship between suicidality and indices of HIV outcomes. Results Majority of the participants were female and the participant mean age was 35 years. Most of them (73%) had primary or no formal education. The proportion of participants with suicidality decreased from 2.9% at baseline to roughly 1% both at month 6 and month 12. Of the investigated clinical and behavioural outcomes, baseline suicidality only had a negative impact on missing a dose of ART where the odds of missing a dose of ART were 8.25 (95% CI 2.45–27.71, p〉0.01) times higher for participants with suicidality compared to those without suicidality. The following outcomes were not significantly impacted by baseline suicidality: HIV clinical stage, CD4 count and risky sexual behaviour. Conclusions The fact that baseline suicidality significantly negatively impacted ART adherence calls for the incorporation of psychosocial interventions to target indices of psychological distress such as suicidality to improve HIV related outcomes.

Description: The number of fatalities in the construction industry is highest among all industries; thus, various losses in the form of fatalities in construction represent a significant factor for safety management. If a fatality occurs, it is important to estimate the overall loss, as a significant financial loss occurs for each project participant. However, in studies of the cost of accidents involving a fatality conducted abroad, the framework cannot be applied as it is because insurance types, systems, and legal cost systems differ by country. Therefore, we developed a framework for calculating the fatality loss considering various aspects of labor, industry, and regulations in Korea. This was done in four steps: (i) data collection and criteria selection; (ii) proposed framework development; (iii) conduct of questionnaire surveys for the case study; and (iv) analysis and evaluation of the case study. As a result of the data analysis after the case study of general construction companies, the total fatality loss was estimated to be 2,198,260 USD/person. The contributions of this study are the development of a framework composed of newly discovered items that can acquire reliable data in consideration of the properties of the construction industry.

Description: Objective. The main objective of this study was to investigate the relationship between poverty, religion, and suicidal thoughts among U.S. youth. The disparities regarding gender, race, and ethnicity with regard to suicidal thoughts were also assessed. Methods. A cross-sectional correlational research design was used for this study and a national representative sample of 1945 young adults aged 18 to 25 was selected from the 2014 National Survey on Drug Use and Health. Logistic regression analysis with interaction effects was utilized to determine if poverty and religion were associated with suicidal thoughts. Results. About 43 percent of the sample reported having suicidal thoughts when things got worse and this prevalence rate varied by gender and race/ethnicity with white males self-disclosing the highest rate of suicidal thoughts. After adjusting for demographic and socioeconomic characteristics, black males who lived up to two times the poverty line had a higher likelihood of suicidal thoughts (p = 0.011), and religion protected against suicidal thoughts (p = 0.012). Youth with lower education and poor health were more inclined to have suicidal thoughts than their peers. Conclusions. Suicide is the second leading cause of death for American young adults aged 18 to 25. Understanding these differences between social determinants of suicide can help public health researchers strategize how to make evidence-based recommendations for suicide prevention efforts.

Description: Gram-negative bacteria take up the essential ion Fe3+ as ferric-siderophore complexes through their outer membrane using TonB-dependent transporters. However, the subsequent route through the inner membrane differs across many bacterial species and siderophore chemistries and is not understood in detail. Here, we report the crystal structure of the inner membrane protein FoxB (from Pseudomonas aeruginosa) that is involved in Fe-siderophore uptake. The structure revealed a fold with two tightly bound heme molecules. In combination with in vitro reduction assays and in vivo iron uptake studies, these results establish FoxB as an inner membrane reductase involved in the release of iron from ferrioxamine during Fe-siderophore uptake.

Description: Background The COVID-19 vaccination campaign in the US has been immensely successful in vaccinating those who are receptive, further increases in vaccination rates however will require more innovative approaches to reach those who remain hesitant. Developing vaccination strategies that are modelled on what people want could further increase uptake. Methods and findings To inform COVID-19 vaccine distribution strategies that are aligned with public preferences we conducted a discrete choice experiment among the US public (N = 2,895) between March 15 to March 22, 2021. We applied sampling weights, evaluated mean preferences using mixed logit models, and identified latent class preference subgroups. On average, the public prioritized ease, preferring single to two dose vaccinations (mean preference: -0.29; 95%CI: -0.37 to -0.20), vaccinating once rather than annually (mean preference: -0.79; 95%CI: -0.89 to -0.70) and reducing waiting times at vaccination sites. Vaccine enforcement reduced overall vaccine acceptance (mean preference -0.20; 95%CI: -0.30 to -0.10), with a trend of increasing resistance to enforcement with increasing vaccine hesitancy. Latent class analysis identified four distinct preference phenotypes: the first prioritized inherent “vaccine features” (46.1%), the second were concerned about vaccine “service delivery” (8.8%), a third group desired “social proof” of vaccine safety and were susceptible to enforcement (13.2%), and the fourth group were “indifferent” to vaccine and service delivery features and resisted enforcement (31.9%). Conclusions This study identifies several critical insights for the COVID-19 public health response. First, identifying preference segments is essential to ensure that vaccination services meet the needs of diverse population subgroups. Second, making vaccination easy and promoting autonomy by simplifying services and offering the public choices (where feasible) may increase uptake in those who remain deliberative. And, third vaccine mandates have the potential to increase vaccination rates in susceptible groups but may simultaneously promote control aversion and resistance in those who are most hesitant.

Description: Introduction The single-leg heel raise test (SLHR) is commonly used in clinical settings to approximate plantar flexor strength, yet this is neither validated nor supported physiologically. The purposes of this study were to: determine (1) associations between SLHR repetitions, maximal plantar flexor strength, and reductions in strength; and (2) whether sex differences exist in performance of the SLHR. Methods Twenty-eight young, healthy participants (14 males,14 females, 19–30 years) performed repeated single-leg heel raises to task failure. Pre- and post-task measures included maximal voluntary isometric contractions (MVIC), and voluntary activation and contractile properties of the plantar flexor muscles, assessed using peripheral electrical stimulation of the tibial nerve. Surface electromyography was recorded for the medial and lateral gastrocnemius, soleus, and anterior tibialis muscles. Results The SLHR resulted in 20.5% reductions in MVIC torque (p

Description: We consider a nonlinear autonomous system of N≫1 degrees of freedom randomly coupled by both relaxational (“gradient”) and nonrelaxational (“solenoidal”) random interactions. We show that with increased interaction strength, such systems generically undergo an abrupt transition from a trivial phase portrait with a single stable equilibrium into a topologically nontrivial regime of “absolute instability” where equilibria are on average exponentially abundant, but typically, all of them are unstable, unless the dynamics is purely gradient. When interactions increase even further, the stable equilibria eventually become on average exponentially abundant unless the interaction is purely solenoidal. We further calculate the mean proportion of equilibria that have a fixed fraction of unstable directions.

Description: Humans and nonhuman animals display conformist as well as anticonformist biases in cultural transmission. Whereas many previous mathematical models have incorporated constant conformity coefficients, empirical research suggests that the extent of (anti)conformity in populations can change over time. We incorporate stochastic time-varying conformity coefficients into a widely used conformity model, which assumes a fixed number n of “role models” sampled by each individual. We also allow the number of role models to vary over time (nt). Under anticonformity, nonconvergence can occur in deterministic and stochastic models with different parameter values. Even if strong anticonformity may occur, if conformity or random copying (i.e., neither conformity nor anticonformity) is expected, there is convergence to one of the three equilibria seen in previous deterministic models of conformity. Moreover, this result is robust to stochastic variation in nt. However, dynamic properties of these equilibria may be different from those in deterministic models. For example, with random conformity coefficients, all equilibria can be stochastically locally stable simultaneously. Finally, we study the effect of randomly changing weak selection. Allowing the level of conformity, the number of role models, and selection to vary stochastically may produce a more realistic representation of the wide range of group-level properties that can emerge under (anti)conformist biases. This promises to make interpretation of the effect of conformity on differences between populations, for example those connected by migration, rather difficult. Future research incorporating finite population sizes and migration would contribute added realism to these models.

Description: Stream temperature science and management is rapidly shifting from single-metric driven approaches to multi-metric, thermal regime characterizations of streamscapes. Given considerable investments in recovery of cold-water fisheries (e.g., Pacific salmon and other declining native species), understanding where cold water is likely to persist, and how cold-water thermal regimes vary, is critical for conservation. California’s unique position at the southern end of cold-water ecosystems in the northern hemisphere, variable geography and hydrology, and extensive flow regulation requires a systematic approach to thermal regime classification. We used publicly available, long-term (〉 8 years) stream temperature data from 77 sites across California to model their thermal regimes, calculate three temperature metrics, and use the metrics to classify each regime with an agglomerative nesting algorithm. Then, we assessed the variation in each class and considered underlying physical or anthropogenic factors that could explain differences between classes. Finally, we considered how different classes might fit existing criteria for cool- or cold-water thermal regimes, and how those differences complicate efforts to manage stream temperature through regulation. Our results demonstrate that cool- and cold-water thermal regimes vary spatially across California. Several salient findings emerge from this study. Groundwater-dominated streams are a ubiquitous, but as yet, poorly explored class of thermal regimes. Further, flow regulation below dams imposes serial discontinuities, including artificial thermal regimes on downstream ecosystems. Finally, and contrary to what is often assumed, California reservoirs do not contain sufficient cold-water storage to replicate desirable, reach-scale thermal regimes. While barriers to cold-water conservation are considerable and the trajectory of cold-water species towards extinction is dire, protecting reaches that demonstrate resilience to climate warming remains worthwhile.

Description: This paper investigated the appropriate specifications of Engel curves for non-food expenditure categories and estimated the deprivation indices of non-food needs in rural areas using a semi parametric examination of the presence of saturation points. The study used the extended partial linear model (EPLM) and adopted two estimation methods—the double residual estimator and differencing estimator—to obtain flexible shapes across different expenditure categories and estimate equivalence scales. We drew on data of the Egyptian Household Income, Expenditure, and Consumption Survey (HIEC). Our paper provides empirical evidence that the rankings of most non-food expenditure categories is of rank three at most. Rural households showed high economies of scale in non-food consumption, with child’s needs accounting for only 10% of adult’s non-food needs. Based on semi-parametrically estimated consumption behavior, the tendency of non-food expenditure categories to saturate did not emerge. While based on parametrically estimated consumption behavior, rural areas exhibited higher deprivation indices in terms of health and education expenditure categories, which indicates the need to design specific programs economically targeting such vulnerable households.

Description: Menzerath’s law is a quantitative linguistic law which states that, on average, the longer is a linguistic construct, the shorter are its constituents. In contrast, Menzerath-Altmann’s law (MAL) is a precise mathematical power-law-exponential formula which expresses the expected length of the linguistic construct conditioned on the number of its constituents. In this paper, we investigate the anatomy of MAL for constructs being word tokens and constituents being syllables, measuring its length in graphemes. First, we derive the exact form of MAL for texts generated by the memoryless source with three emitted symbols, which can be interpreted as a monkey typing model or a null model. We show that this null model complies with Menzerath’s law, revealing that Menzerath’s law itself can hardly be a criterion of complexity in communication. This observation does not apply to the more precise Menzerath-Altmann’s law, which predicts an inverted regime for sufficiently range constructs, i.e., the longer is a word, the longer are its syllables. To support this claim, we analyze MAL on data from 21 languages, consisting of texts from the Standardized Project Gutenberg. We show the presence of the inverted regime, not exhibited by the null model, and we demonstrate robustness of our results. We also report the complicated distribution of syllable sizes with respect to their position in the word, which might be related with the emerging MAL. Altogether, our results indicate that Menzerath’s law—in terms of correlations—is a spurious observation, while complex patterns and efficiency dynamics should be rather attributed to specific forms of Menzerath-Altmann’s law.

Description: Temperate grassland soils store significant amounts of carbon (C). Estimating how much livestock grazing and manuring can influence grassland soil organic carbon (SOC) is key to improve greenhouse gas grassland budgets. The Rothamsted Carbon (RothC) model, although originally developed and parameterized to model the turnover of organic C in arable topsoil, has been widely used, with varied success, to estimate SOC changes in grassland under different climates, soils, and management conditions. In this paper, we hypothesise that RothC-based SOC predictions in managed grasslands under temperate moist climatic conditions can be improved by incorporating small modifications to the model based on existing field data from diverse experimental locations in Europe. For this, we described and evaluated changes at the level of: (1) the soil water function of RothC, (2) entry pools accounting for the degradability of the exogenous organic matter (EOM) applied (e.g., ruminant excreta), (3) the month-on-month change in the quality of C inputs coming from plant residues (i.e above-, below-ground plant residue and rhizodeposits), and (4) the livestock trampling effect (i.e., poaching damage) as a common problem in areas with higher annual precipitation. In order to evaluate the potential utility of these changes, we performed a simple sensitivity analysis and tested the model predictions against averaged data from four grassland experiments in Europe. Our evaluation showed that the default model’s performance was 78% and whereas some of the modifications seemed to improve RothC SOC predictions (model performance of 95% and 86% for soil water function and plant residues, respectively), others did not lead to any/or almost any improvement (model performance of 80 and 46% for the change in the C input quality and livestock trampling, respectively). We concluded that, whereas adding more complexity to the RothC model by adding the livestock trampling would actually not improve the model, adding the modified soil water function and plant residue components, and at a lesser extent residues quality, could improve predictability of the RothC in managed grasslands under temperate moist climatic conditions.

Description: Usutu virus (USUV) is an emerging arbovirus in Europe that has been increasingly identified in asymptomatic humans and donated blood samples and is a cause of increased incidents of neuroinvasive human disease. Treatment or prevention options for USUV disease are currently nonexistent, the result of a lack of understanding of the fundamental elements of USUV pathogenesis. Here, we report two structures of the mature USUV virus, determined at a resolution of 2.4 Å, using single-particle cryogenic electron microscopy. Mature USUV is an icosahedral shell of 180 copies of envelope (E) and membrane (M) proteins arranged in the classic herringbone pattern. However, unlike previous reports of flavivirus structures, we observe virus subpopulations and differences in the fusion loop disulfide bond. Presence of a second, unique E glycosylation site could elucidate host interactions, contributing to the broad USUV tissue tropism. The structures provide a basis for exploring USUV interactions with glycosaminoglycans and lectins, the role of the RGD motif as a receptor, and the inability of West Nile virus therapeutic antibody E16 to neutralize the mature USUV strain SAAR-1776. Finally, we identify three lipid binding sites and predict key residues that likely participate in virus stability and flexibility during membrane fusion. Our findings provide a framework for the development of USUV therapeutics and expand the current knowledge base of flavivirus biology.

Description: The success of unmanned car, an emerging tool of transportation with so many advantages, depends to a large extent on its user acceptability. Potential designers are both the decision makers of driverless car design and the users of driverless cars. This study aims to explore the influencing factors of the potential designers’ intention to use unmanned cars. Based on the theory of Technology Acceptance Model (TAM), this study further expanded the TAM by incorporating perceived trust, perceived enjoyment and self-efficacy, so as to explain and predict potential designers’ intention to use unmanned cars. The questionnaire is determined through theoretical literature, pre-tests, etc., and the Structural Equation Model is used to analyze the data of 202 valid survey samples to investigate the influencing factors of the willingness to use unmanned vehicles. The results show that potential designers’ intention to use unmanned cars is positively affected by perceived trust, perceived enjoyment, perceived usefulness and perceived ease of use, and perceived trust has a positive effect on perceived ease of use, self-efficacy and perceived ease of use also have a positive effect on perceived usefulness. The findings of this study can provide designers and developers of unmanned cars, policy makers and implementers with guidance in the follow-up design, policy formulation and advertising of unmanned cars.

Description: Global value chains are formed through value-added trade, and some regions promote economic integration by concluding regional trade agreements to promote these chains. However, it has not been established to quantitatively assess the scope and extent of economic integration involving various sectors in multiple countries. In this study, we used the World Input–Output Database to create a cross-border sector-wise network of trade in value-added (international value-added network) covering the period of 2000–2014 and evaluated them using network science methods. By applying Infomap to the international value-added network, we confirmed two regional communities: Europe and the Pacific Rim. We applied Helmholtz–Hodge decomposition to the value-added flows within the region into potential and circular flows, and clarified the annual evolution of the potential and circular relationships between countries and sectors. The circular flow component of the decomposition was used to define an economic integration index. Findings confirmed that the degree of economic integration in Europe declined sharply after the economic crisis in 2009 to a level lower than that in the Pacific Rim. The European economic integration index recovered in 2011 but again fell below that of the Pacific Rim in 2013. Moreover, sectoral economic integration indices suggest what Europe depends on Russia in natural resources makes the European economic integration index unstable. On the other hand, the indices of the Pacific Rim suggest the steady economic integration index of the Pacific Rim captures the stable global value chains from natural resources to construction and manufactures of motor vehicles and high-tech products.

Description: The aims of this study were (1) to design a user-friendly instrument to assess and optimize patient information material (PIM), (2) to develop an English version, and (3) to test its psychometric properties. The instrument was needed to optimize the top-down developed PIM of the psycho-oncological care programme isPO. First, a literature-based PIM checklist was developed by a team of patient representatives, cancer care experts and professional researchers. Next, the checklist’s reliability and validity were analysed by having cancer survivors assess the initial and optimized version of the isPO-leaflet. The User-friendly Patient Information Material Checklist (UPIM-Check), developed participatorily, was found to be effective for evaluating PIM. It uses a traffic light scale, and suggestions for improvement can be given for each criterion. Its reliability appeared to be excellent (α = 0.927). The optimized leaflet was rated significantly better than the initial one. The UPIM-Check is a reliable and valid instrument, which enables end-users (e.g., patients) to assess and optimize the quality of PIM according to scientific criteria and the needs of end-users. A bottom-up approach was essential for developing and validating the UPIM-Check. End-users constantly contributed with their specific knowledge. Thus, their position as co-researchers was significantly strengthened.

Description: Background COPD and asthma exacerbations result in many emergency department admissions. Not all treatments are successful, often leading to hospital readmissions. Aims We sought to develop predictive models for exacerbation treatment outcome in a cohort of exacerbating asthma and COPD patients presenting to the emergency department. Methods Treatment failure was defined as the need for additional systemic corticosteroids (SCS) and/or antibiotics, hospital readmissison or death within 30 days of initial emergency department visit. We performed univariate analysis comparing characteristics of patients either given or not given SCS at exacerbation and of patients who succeeded versus failed treatment. Patient demographics, medications and exacerbation symptoms, physiology and biology were available. We developed multivariate random forest models to identify predictors of SCS prescription and for predicting treatment failure. Results Data were available for 81 patients, 43 (53%) of whom failed treatment. 64 (79%) of patients were given SCS. A random forest model using presence of wheeze at exacerbation and blood eosinophil percentage predicted SCS prescription with area under receiver operating characteristic curve (AUC) 0.69. An 11 variable random forest model (which included medication, previous exacerbations, symptoms and quality of life scores) could predict treatment failure with AUC 0.81. A random forest model using just the two best predictors of treatment failure, namely, visual analogue scale for breathlessness and sputum purulence, predicted treatment failure with AUC 0.68. Conclusion Prediction of exacerbation treatment outcome can be achieved via supervised machine learning combining different predictors at exacerbation. Validation of our predictive models in separate, larger patient cohorts is required.

Description: Regulation systems for fluid-driven soft robots predominantly consist of inflexible and bulky components. These rigid structures considerably limit the adaptability and mobility of these robots. Soft valves in various forms for fluidic actuators have been developed, primarily fluidically or electrically driven. However, fluidic soft valves require external pressure sources that limit robot locomotion. State-of-the-art electrostatic valves are unable to modulate pressure beyond 3.5 kPa with a sufficient flow rate (〉6 mL⋅min−1). In this work, we present an electrically powered soft valve for hydraulic actuators with mesoscale channels based on a different class of ultrahigh-power density dynamic dielectric elastomer actuators. The dynamic dielectric elastomer actuators (DEAs) are actuated at 500 Hz or above. These DEAs generate 300% higher blocked force compared with the dynamic DEAs in previous works and their loaded power density reaches 290 W⋅kg−1 at operating conditions. The soft valves are developed with compact (7 mm tall) and lightweight (0.35 g) dynamic DEAs, and they allow effective control of up to 51 kPa of pressure and a 40 mL⋅min−1 flow rate with a response time less than 0.1 s. The valves can also tune flow rates based on their driving voltages. Using the DEA soft valves, we demonstrate control of hydraulic actuators of different volumes and achieve independent control of multiple actuators powered by a single pressure source. This compact and lightweight DEA valve is capable of unprecedented electrical control of hydraulic actuators, showing the potential for future onboard motion control of soft fluid-driven robots.

Description: Metapopulation capacity provides an analytic tool to quantify the impact of landscape configuration on metapopulation persistence, which has proven powerful in biological conservation. Yet surprisingly few efforts have been made to apply this approach to multispecies systems. Here, we extend metapopulation capacity theory to predict the persistence of trophically interacting species. Our results demonstrate that metapopulation capacity could be used to predict the persistence of trophic systems such as prey–predator pairs and food chains in fragmented landscapes. In particular, we derive explicit predictions for food chain length as a function of metapopulation capacity, top-down control, and population dynamical parameters. Under certain assumptions, we show that the fraction of empty patches for the basal species provides a useful indicator to predict the length of food chains that a fragmented landscape can support and confirm this prediction for a host–parasitoid interaction. We further show that the impact of habitat changes on biodiversity can be predicted from changes in metapopulation capacity or approximately by changes in the fraction of empty patches. Our study provides an important step toward a spatially explicit theory of trophic metacommunities and a useful tool for predicting their responses to habitat changes.

Description: Visual cognitive strategies in construction hazard recognition (CHR) signifies prominent value for the development of CHR computer vision techniques and safety training. Nonetheless, most studies are based on either sparse fixations or cross-sectional (accumulative) statistics, which lack consideration of temporality and yielding limited visual pattern information. This research aims to investigate the temporal visual search patterns for CHR and the cognitive strategies they imply. An experimental study was designed to simulate CHR and document participants’ visual behavior. Temporal qualitative comparative analysis (TQCA) was applied to analyze the CHR visual sequences. The results were triangulated based on post-event interviews and show that: (1) In the potential electrical contact hazards, the intersection of the energy-releasing source and wire that reflected their interaction is the cognitively driven visual area that participants tend to prioritize; (2) in the PPE-related hazards, two different visual strategies, i.e., “scene-related” and “norm-guided”, can usually be generalized according to the participants’ visual cognitive logic, corresponding to the bottom-up (experience oriented) and top-down (safety knowledge oriented) cognitive models. This paper extended recognition-by-components (RBC) model and gestalt model as well as providing feasible practical guide for safety trainings and theoretical foundations of computer vision techniques for CHR.

Description: Introduction The concept of death is abstract, complex and has a number of meanings. Thus, its understanding and the approach taken to it depend, to a large extent, on aspects such as age, culture, training and religion. Nursing students have regular contact with the process of death and so it is of great interest to understand the attitudes they have towards it. As we live in a plural society it is even more interesting to not only understand the attitudes of Spanish students but, also, those of students coming from other countries. In the present article, we seek to identify and compare the attitudes held by nursing degree students at Hekima-Santé University (Senegal) and the University of Huelva (Spain) about end of life processes. The study identifies elements that condition attitudes and coping with death, whilst considering curricular differences with regards to specific end of life training. Method A descriptive, cross-sectional and multi-center study was conducted. The overall sample (N = 142) was divided into groups: Hekima-Santé University (Dakar, Senegal) and the University of Huelva (Huelva, Spain). The measurement instruments used were an ad-hoc questionnaire and Bugen´s Coping with Death Scale. Results Statistically significant differences (p = 0.005, 95%CI) were found in relation to overall Bugen Scale scores. We can confirm that specialized end of life training (University of Huelva, Spain) did not lead to better coping when compared with a population whose academic curriculum did not provide specific training and who engaged in more religious practices (Hekima-Santé University, Senegal). Conclusions In cultures where religion not only influences the spiritual dimension of the individual, but acts in the ethical and moral system and consequently in the economic, educational and family sphere, the accompaniment at the end of life transcends the formative plane. Considering the plural society in which we live, the training that integrates the Degree in Nursing with regard to the care of the final process, must be multidimensional in which spirituality and faith are integrated, working emotional and attentional skills, as well as cultural competence strategies in this process.

Description: Introduction Absenteeism of frontline health workers in public sector facilities is widespread in low-income countries. There is little quantitative evidence on how health worker absenteeism influences patient treatment seeking behavior, though low public sector utilization and heavy reliance on the informal sector are well documented in low-income settings. Methods Using a unique panel dataset covering health facilities and households over a 10-month period in Uganda, we investigate the extent to which health worker absenteeism (defined as zero health workers present at a health facility) impacts patient care seeking behavior, testing, and treatment. Results We find high rates of health worker absenteeism at public sector health facilities, with most of the absenteeism occurring at lower level public health clinics. On average, no health worker was present in 42% of all days monitored in lowest level public health clinics, whereas this number was less than 5% in high level public hospitals and private facilities. In our preferred empirical model with household fixed effects, we find that health worker absenteeism reduces the odds that a patient seeks care in the public sector (OR = 0.65, 95% CI = 0.44–0.95) and receives malaria testing (OR = 0.73, 95% CI = 0.53–0.99) and increases the odds of paying out-of-pocket for treatment (OR = 1.41, 95% CI = 1.10–1.80). The estimated differences in care-seeking are larger for children under-five than for the overall study population. Conclusions The impact of health worker absenteeism on the quality of care received as well as the financial burden faced by households in sub-Saharan Africa is substantial.

Description: Braiding of topological structures in complex matter fields provides a robust framework for encoding and processing information, and it has been extensively studied in the context of topological quantum computation. In living systems, topological defects are crucial for the localization and organization of biochemical signaling waves, but their braiding dynamics remain unexplored. Here, we show that the spiral wave cores, which organize the Rho-GTP protein signaling dynamics and force generation on the membrane of starfish egg cells, undergo spontaneous braiding dynamics. Experimentally measured world line braiding exponents and topological entropy correlate with cellular activity and agree with predictions from a generic field theory. Our analysis further reveals the creation and annihilation of virtual quasi-particle excitations during defect scattering events, suggesting phenomenological parallels between quantum and living matter.

Description: This study empirically explored the activity profiles of Korean older adults by considering a wide range of activities simultaneously and further investigated the socioeconomic factors associated with activity profiles. Gender differences in activity profiles were examined in-depth. Latent class analysis (LCA) was used to identify activity profiles based on a nationally representative sample of older adults from the most recent two waves of the Korean Time Use Survey (n = 3034 for 2014 and n = 3960 for 2019). Multinomial logistic regression analysis was employed to further examine the factors associated with the activity profiles. The findings revealed four distinct activity groups, although there were differences in activity profiles between the two waves. Several sociodemographic factors, such as gender, age, assets and income, were significantly associated with the activity profiles. Findings from this study can inform policy makers seeking interventions that enhance the overall well-being of older adults through activity engagement.

Description: Psychological distress and psychosocial factors are studied in the sports context in players of various specialties, but are only little studied with coaches who carry out their work with these athletes; that is where we put the emphasis, trying to determine the perception of coaches on psychological distress and psychosocial risk factors that may influence their sports work in times of a pandemic. It is an ex post facto study with a single-group retrospective design, with a representative sample of 94 coaches out of a possible 109. The Kessler Psychological Distress Scale and the short version of the ISTAS21 Psychosocial Risk Assessment at Work Questionnaire were adapted to the sports context. The results show that the youngest, those with the least experience and level 1 and level 2 coaches show the highest levels of stress. According to the psychosocial risk assessment, level 1 and 2 coaches, with experience between 6 to 10 years, are in the risk zone. Therefore, it is important to work with a group of coaches who are in the psychosocial risk zone and with high levels of psychological discomfort in order to avoid mental, emotional and physical stress, for the good performance of their work in the best possible conditions.

Description: Identification of causal variants and genes underlying genome-wide association study (GWAS) loci is essential to understand the biology of alcohol use disorder (AUD) and drinks per week (DPW). Multi-omics integration approaches have shown potential for fine mapping complex loci to obtain biological insights to disease mechanisms. In this study, we use multi-omics approaches, to fine-map AUD and DPW associations at single SNP resolution to demonstrate that rs56030824 on chromosome 11 significantly reduces SPI1 mRNA expression in myeloid cells and lowers risk for AUD and DPW. Our analysis also identifies MAPT as a candidate causal gene specifically associated with DPW. Genes prioritized in this study show overlap with causal genes associated with neurodegenerative disorders. Multi-omics integration analyses highlight, genetic similarities and differences between alcohol intake and disordered drinking, suggesting molecular heterogeneity that might inform future targeted functional and cross-species studies.

Description: Graphene-based photodetectors have attracted significant attention for high-speed optical communication due to their large bandwidth, compact footprint, and compatibility with silicon-based photonics platform. Large-bandwidth silicon-based optical coherent receivers are crucial elements for large-capacity optical communication networks with advanced modulation formats. Here, we propose and experimentally demonstrate an integrated optical coherent receiver based on a 90-degree optical hybrid and graphene-on-plasmonic slot waveguide photodetectors, featuring a compact footprint and a large bandwidth far exceeding 67 GHz. Combined with the balanced detection, 90 Gbit/s binary phase-shift keying signal is received with a promoted signal-to-noise ratio. Moreover, receptions of 200 Gbit/s quadrature phase-shift keying and 240 Gbit/s 16 quadrature amplitude modulation signals on a single-polarization carrier are realized with a low additional power consumption below 14 fJ/bit. This graphene-based optical coherent receiver will promise potential applications in 400-Gigabit Ethernet and 800-Gigabit Ethernet technology, paving another route for future high-speed coherent optical communication networks.

Description: An overarching challenge of the electrochemical carbon dioxide reduction reaction (eCO2RR) is finding an earth-abundant, highly active catalyst that selectively produces hydrocarbons at relatively low overpotentials. Here, we report the eCO2RR performance of two-dimensional transition metal carbide class of materials. Our results indicate a maximum methane (CH4) current density of −421.63 mA/cm2 and a CH4 faradic efficiency of 82.7% ± 2% for di-tungsten carbide (W2C) nanoflakes in a hybrid electrolyte of 3 M potassium hydroxide and 2 M choline-chloride. Powered by a triple junction photovoltaic cell, we demonstrate a flow electrolyzer that uses humidified CO2 to produce CH4 in a 700-h process under one sun illumination with a CO2RR energy efficiency of about 62.3% and a solar-to-fuel efficiency of 20.7%. Density functional theory calculations reveal that dissociation of water, chemisorption of CO2 and cleavage of the C-O bond—the most energy consuming elementary steps in other catalysts such as copper—become nearly spontaneous at the W2C surface. This results in instantaneous formation of adsorbed CO—an important reaction intermediate—and an unlimited source of protons near the tungsten surface sites that are the main reasons for the observed superior activity, selectivity, and small potential.

Description: The contents of numerous membrane lipids change upon ageing. However, it is unknown whether and how any of these changes are causally linked to lifespan regulation. Acyl chains contribute to the functional specificity of membrane lipids. In this study, working with C. elegans, we identified an acyl chain-specific sphingolipid, C22 glucosylceramide, as a longevity metabolite. Germline deficiency, a conserved lifespan-extending paradigm, induces somatic expression of the fatty acid elongase ELO-3, and behenic acid (22:0) generated by ELO-3 is incorporated into glucosylceramide for lifespan regulation. Mechanistically, C22 glucosylceramide is required for the membrane localization of clathrin, a protein that regulates membrane budding. The reduction in C22 glucosylceramide impairs the clathrin-dependent autophagic lysosome reformation, which subsequently leads to TOR activation and longevity suppression. These findings reveal a mechanistic link between membrane lipids and ageing and suggest a model of lifespan regulation by fatty acid-mediated membrane configuration.

Description: Reactive oxygen species (ROS) oxidize cellular nucleotide pools and cause double strand breaks (DSBs). Non-homologous end-joining (NHEJ) attaches broken chromosomal ends together in mammalian cells. Ribonucleotide insertion by DNA polymerase (pol) μ prepares breaks for end-joining and this is required for successful NHEJ in vivo. We previously showed that pol μ lacks discrimination against oxidized dGTP (8-oxo-dGTP), that can lead to mutagenesis, cancer, aging and human disease. Here we reveal the structural basis for proficient oxidized ribonucleotide (8-oxo-rGTP) incorporation during DSB repair by pol μ. Time-lapse crystallography snapshots of structural intermediates during nucleotide insertion along with computational simulations reveal substrate, metal and side chain dynamics, that allow oxidized ribonucleotides to escape polymerase discrimination checkpoints. Abundant nucleotide pools, combined with inefficient sanitization and repair, implicate pol μ mediated oxidized ribonucleotide insertion as an emerging source of widespread persistent mutagenesis and genomic instability.

Description: Previous studies have suggested that PTEN loss is associated with p110β signaling dependency, leading to the clinical development of p110β-selective inhibitors. Here we use a panel pre-clinical models to reveal that PI3K isoform dependency is not governed by loss of PTEN and is impacted by feedback inhibition and concurrent PIK3CA/PIK3CB alterations. Furthermore, while pan-PI3K inhibition in PTEN-deficient tumors is efficacious, upregulation of Insulin Like Growth Factor 1 Receptor (IGF1R) promotes resistance. Importantly, we show that this resistance can be overcome through targeting AKT and we find that AKT inhibitors are superior to pan-PI3K inhibition in the context of PTEN loss. However, in the presence of wild-type PTEN and PIK3CA-activating mutations, p110α-dependent signaling is dominant and selectively inhibiting p110α is therapeutically superior to AKT inhibition. These discoveries reveal a more nuanced understanding of PI3K isoform dependency and unveil novel strategies to selectively target PI3K signaling nodes in a context-specific manner.

Description: Non-invasive approaches for cell-free DNA (cfDNA) assessment provide an opportunity for cancer detection and intervention. Here, we use a machine learning model for detecting tumor-derived cfDNA through genome-wide analyses of cfDNA fragmentation in a prospective study of 365 individuals at risk for lung cancer. We validate the cancer detection model using an independent cohort of 385 non-cancer individuals and 46 lung cancer patients. Combining fragmentation features, clinical risk factors, and CEA levels, followed by CT imaging, detected 94% of patients with cancer across stages and subtypes, including 91% of stage I/II and 96% of stage III/IV, at 80% specificity. Genome-wide fragmentation profiles across ~13,000 ASCL1 transcription factor binding sites distinguished individuals with small cell lung cancer from those with non-small cell lung cancer with high accuracy (AUC = 0.98). A higher fragmentation score represented an independent prognostic indicator of survival. This approach provides a facile avenue for non-invasive detection of lung cancer.

Description: The discovery of moiré superlattices (MSLs) opened an era in the research of ‘twistronics’. Engineering MSLs and realizing unique emergent properties are key challenges. Herein, we demonstrate an effective synthetic strategy to fabricate MSLs based on mechanical flexibility of WS2 nanobelts by a facile one-step hydrothermal method. Unlike previous MSLs typically created through stacking monolayers together with complicated method, WS2 MSLs reported here could be obtained directly during synthesis of nanobelts driven by the mechanical instability. Emergent properties are found including superior conductivity, special superaerophobicity and superhydrophilicity, and strongly enhanced electro-catalytic activity when we apply ‘twistronics’ to the field of catalytic hydrogen production. Theoretical calculations show that such excellent catalytic performance could be attributed to a closer to thermoneutral hydrogen adsorption free energy value of twisted bilayers active sites. Our findings provide an exciting opportunity to design advanced WS2 catalysts through moiré superlattice engineering based on mechanical flexibility.

Description: Suicide represents a very important issue in public health. For approaching attitudes toward suicide, we have developed an instrument that, following previous recommendations, assesses specific thoughts related to the perception of suicide utility in the press. First of all, we will test the psychometric properties of the scale we created ad hoc for assessing suicide utility perception. After that, we expect to find that the suicide utility perception in the press will have a statistically significant impact on positive attitudes toward terminally ill patients’ suicide (Hypothesis 1). In addition, this relationship will be mediated by suicide legitimation (Hypothesis 2). This mediation will be moderated by depressive symptomatology (Hypothesis 3). The sample was composed of 66 Spanish participants. Suicide legitimation was significantly related to the positive evaluation of terminally ill people’s euthanasia. Finally, when the levels of depression’s psychological concomitants increased, the support for terminally ill people’s euthanasia increased as well. Implications and limitations have been discussed.

Description: Patient-controlled epidural analgesia is widely used to control postoperative pain following major intra-abdominal surgeries. However, determining the optimal infusion dose that can produce effective analgesia while reducing side effects remains a task to be solved. Postoperative pain and adverse effects between variable-rate feedback infusion (VFIM group, n = 36) and conventional fixed-rate basal infusion (CFIM group, n = 36) of fentanyl/ropivacaine-based patient-controlled epidural analgesia were evaluated. In the CFIM group, the basal infusion rate was fixed (5 mL/h), whereas, in the VFIM group, the basal infusion rate was increased by 0.5 mL/h each time a bolus dose was administered and decreased by 0.3 mL/h when a bolus dose was not administered for 2 h. Patients in the VFIM group experienced significantly less pain at one to six hours after surgery than those in the CFIM group. Further, the number of patients who suffered from postoperative nausea was significantly lower in the VFIM group than in the CFIM group until six hours after surgery. The variable-rate feedback infusion mode of patient-controlled epidural analgesia may provide better analgesia accompanied with significantly less nausea in the early postoperative period than the conventional fixed-rate basal infusion mode following open gastrectomy.

Description: Malaria is still a global health problem. Plasmodium is a single-cell protozoan parasite that causes malaria and is transmitted to humans through the female Anopheles mosquito. The previous study showed that Sonchus arvensis L. callus has antiplasmodial activity. Several treatments are needed for callus quality improvement for antimalarial compound production. This study aimed to examine the effect of dolomite [CaMg(CO3)2] on growth (morpho-anatomical structure and biomass), secondary metabolite production, and in vitro antiplasmodial activity of S. arvensis L. callus. In this study, leaf explants were grown in Murashige and Skoog medium with a combination of 2,4-dichlorophenoxyacetic acid (2,4-D, one mg/L) and 6-benzyl amino purine (BAP, 0.5 mg/L) with dolomite (50, 75, 100, 150, and 200 mg/L). The 21 days callus ethanolic and methanolic extract were analyzed by gas chromatography-mass spectrometry (GC-MS) and thin-layer chromatography (TLC). The antiplasmodial test was performed on a blood culture infected with Plasmodium falciparum strain 3D7 using the Rieckmann method. The results showed that dolomite significantly affected callus growth, metabolite profile, and in vitro antiplasmodial activity. Dolomite (150 mg/L) showed the highest biomass (0.590 ± 0.136 g fresh weight and 0.074 ± 0.008 g dry weight). GC-MS analysis detected four compounds from callus ethanolic extract. Pelargonic acid, decanoic acid, and hexadecanoic acid were major compounds. One new terpenoid compound is based on TLC analysis. S. arvensis L. callus has antiplasmodial activity with the IC50 value of 5.037 μg/mL. It was three times lower than leaf methanolic extract and five times lower than leaf ethanolic extract.

Description: Linear Parameter Varying (LPV) systems and their control have gained attraction recently as they approximate nonlinear systems with higher order than ordinary linear systems. On the other hand, time delay is an inherent part of various real-life applications. A supervisory control structure is proposed in this paper for LPV systems subject to time delays. In the proposed control structure, a supervisor selects the most suitable controller from a bank of controllers; which desires to enhance the performance of closed-loop system in contrast with using a single robust controller. The analysis is based on the celebrated Smith predictor for time delay compensation and we provide a sufficient condition to assure the stability of the closed-loop switched system in terms of dwell time. Simulations on blood pressure control of hypertension patients in postoperative scenario are used to exemplify the effectiveness of the utilized technique. The operating region of the system is partitioned into five smaller operating regions to construct corresponding robust controllers and perform hysteresis switching amongst them. Simulation results witnessed that the proposed control scheme demonstrated a pressure undershoot less than the desired value of 10 mmHg while the Mean Arterial Pressure (MAP) remains within ±5 mmHg of the desired value.

Description: Background Assessing fitness to drive and predicting driving cessation remains a challenge for primary care physicians using standard screening procedures. The objective of this study was to prospectively evaluate the properties of neuropsychological screening tests, including the Trail Making Test (TMT), Clock Drawing Test (CDT), Montreal Cognitive Assessment (MoCA), Useful Field of View (UFOV), and Timed Up and Go (TUG) test, in predicting driving cessation for health reasons in drivers older than 70 years of age. Design and methods This prospective cohort study, with a median follow-up of 4 years for drivers of 70 years old or older with an active driving license in Switzerland, included 441 participants from a driving refresher course dedicated to volunteer senior drivers. Cases were drivers reported in the national driving registry who lost their license following a health-related accident, who were reported as unfit to drive by their physician or voluntarily ceased driving for health reasons. Survival analysis was used to measure the hazard ratio of driving cessation by adjusting for age and sex and to evaluate the predictive value of combining 3 or more positive tests in predicting driving cessation during a 4-year follow-up. Results A total of 1738 person-years were followed-up in the cohort, with 19 (4.3%) having ceased driving for health reasons. We found that participants with a TMT-A 〈 54 sec and TMT-B 〈 150 sec at baseline had a significantly lower cumulative hazard of driving cessation in 4 years than those with slower performance (adjusted HR 3, 95% CI: 1.16–7.78, p = 0.023). Participants who performed a CDT ≥ 5 had a significantly lower cumulative hazard of driving cessation (adjusted HR 2.89, 95% CI: 1.01–7.71, p = 0.033). Similarly, an MoCA score ≥ 26, TUG test

Description: Host genetic background is a significant driver of the variability in neurological responses to viral infection. Here, we leverage the genetically diverse Collaborative Cross (CC) mouse resource to better understand how chronic infection by Theiler’s Murine Encephalomyelitis Virus (TMEV) elicits diverse clinical and morphologic changes in the central nervous system (CNS). We characterized the TMEV-induced clinical phenotype responses, and associated lesion distributions in the CNS, in six CC mouse strains over a 90 day infection period. We observed varying degrees of motor impairment in these strains, as measured by delayed righting reflex, paresis, paralysis, seizures, limb clasping, ruffling, and encephalitis phenotypes. All strains developed neuroparenchymal necrosis and mineralization in the brain, primarily localized to the hippocampal regions. Two of the six strains presented with axonal degeneration with myelin loss of the nerve roots in the lumbar spinal cord. Moreover, we statistically correlated lesion distribution with overall frequencies of clinical phenotypes and phenotype progression to better understand how and where TMEV targets the CNS, based on genetic background. Specifically, we assessed lesion distribution in relation to the clinical progression of these phenotypes from early to late TMEV disease, finding significant relationships between progression and lesion distribution. Finally, we identified quantitative trait loci associated with frequency of lesions in a particular brain region, revealing several loci of interest for future study: lysosomal trafficking regulator (Lyst) and nidogen 1 (Nid1). Together, these results indicate that the genetic background influences the type and severity of clinical phenotypes, phenotypic resilience to TMEV, and the lesion distribution across strains.

Description: Plant pathogens are responsible for the annual yield loss of crops worldwide and pose a significant threat to global food security. A necessary prelude to many plant disease epidemics is the short-range dispersal of spores, which may generate several disease foci within a field. New information is needed on the mechanisms of plant pathogen spread within and among susceptible plants. Here, we show that self-propelled jumping dew droplets, working synergistically with low wind flow, can propel spores of a fungal plant pathogen (wheat leaf rust) beyond the quiescent boundary layer and disperse them onto neighboring leaves downwind. An array of horizontal water-sensitive papers was used to mimic healthy wheat leaves and showed that up to 25 spores/h may be deposited on a single leaf downwind of the infected leaf during a single dew cycle. These findings reveal that a single dew cycle can disperse copious numbers of fungal spores to other wheat plants, even in the absence of rain splash or strong gusts of wind.

Description: This paper analyzed the degradation pathways of petroleum hydrocarbon degradation bacteria, screened the main degradation pathways, and found the petroleum hydrocarbon degradation enzymes corresponding to each step of the degradation pathway. Through the Copeland method, the best inoculation program of petroleum hydrocarbon degradation bacteria in a polluted site was selected as follows: single oxygenation path was dominated by Streptomyces avermitilis, hydroxylation path was dominated by Methylosinus trichosporium OB3b, secondary oxygenation path was dominated by Pseudomonas aeruginosa, secondary hydroxylation path was dominated by Methylococcus capsulatus, double oxygenation path was dominated by Acinetobacter baylyi ADP1, hydrolysis path was dominated by Rhodococcus erythropolis, and CoA path was dominated by Geobacter metallireducens GS-15 to repair petroleum hydrocarbon contaminated sites. The Copeland method score for this solution is 22, which is the highest among the 375 solutions designed in this paper, indicating that it has the best degradation effect. Meanwhile, we verified its effect by the Cdocker method, and the Cdocker energy of this solution is −285.811 kcal/mol, which has the highest absolute value. Among the inoculation programs of the top 13 petroleum hydrocarbon degradation bacteria, the effect of the best inoculation program of petroleum hydrocarbon degradation bacteria was 18% higher than that of the 13th group, verifying that this solution has the best overall degradation effect. The inoculation program of petroleum hydrocarbon degradation bacteria designed in this paper considered the main pathways of petroleum hydrocarbon pollutant degradation, especially highlighting the degradability of petroleum hydrocarbon intermediate degradation products, and enriching the theoretical program of microbial remediation of petroleum hydrocarbon contaminated sites.

Description: In the field of Differential Evolution (DE), a number of measures have been used to enhance algorithm. However, most of the measures need revision for fitting ensemble of different combinations of DE operators—ensemble DE algorithm. Meanwhile, although ensemble DE algorithm may show better performance than each of its constituent algorithms, there still exists the possibility of further improvement on performance with the help of revised measures. In this paper, we manage to implement measures into Ensemble of Differential Evolution Variants (EDEV). Firstly, we extend the collecting range of optional external archive of JADE—one of the constituent algorithm in EDEV. Then, we revise and implement the Event-Triggered Impulsive (ETI) control. Finally, Linear Population Size Reduction (LPSR) is used by us. Then, we obtain Improved Ensemble of Differential Evolution Variants (IEDEV). In our experiments, good performers in the CEC competitions on real parameter single objective optimization among population-based metaheuristics, state-of-the-art DE algorithms, or up-to-date DE algorithms are involved. Experiments show that our IEDEV is very competitive.

Description: Against the background of the speed-accuracy trade-off, we explored whether the Pace of Life can be used to identify heterogeneity in the strategy to place more weight on either fast or accurate accomplishments. The Pace of Life approaches an individual’s exposure to time and is an intensively studied concept in the evolutionary biology research. Albeit overall rarely, it is increasingly used to understand human behavior and may fulfill many criteria of a personal trait. In a controlled laboratory environment, we measured the participants’ Pace of Life, as well as their performance on a real-effort task. In the real-effort task, the participants had to encode words, whereby each word encoded correctly was associated with a monetary reward. We found that individuals with a faster Pace of Life accomplished more tasks in total. At the same time, they were less accurate and made more mistakes (in absolute terms) than those with a slower Pace of Life. Thus, the Pace of Life seems to be useful to identify an individual’s stance on the speed-accuracy continuum. In our specific task, placing more weight on speed instead of accuracy paid off: Individuals with a faster Pace of Life were ultimately more successful (with regard to their monetary revenue).

Description: Predatory mites in the family Phytoseiidae (Acari: Mesostigmata) are of great importance as biological control agents of pest mites and other arthropods. Correct identification of species is crucial to implement effective biological control of target pests. Here, we provide re-descriptions of seven phytoseiid mite species collected from citrus orchards in Florida. The several important morphological features including dorsal setae lengths, dorsal solenostomes, shape of calyx of spermatheca, chelicera dentition, measurements, and shape of macrosetae on legs currently used to discriminate phytoseiid species were missing in the original descriptions and re-descriptions of these species. Additionally, we observed the presence of a previously unnoted taxonomically important character on Proprioseius meridionalis Chant. Therefore, the re-description was essential for further diagnosis of this species. Accordingly, the validity of the presence/absence of this structure as a diagnostic character to separate species groups in the genus Proprioseius should be re-considered. Furthermore, Typhlodromalus peregrinus, a species for which a series of morphological variations are reported in previous descriptions, is re-described and illustrated from Clermont, Florida, a location very close (10 km) to its type location (Minneola), and the leaves of type host citrus. The macrosetae StIV was knobbed apically in all our specimens of T. peregrinus indicating invalidity of sharp-pointed or knobbed StIV to separate this species from a closely related species, T. aripo De Leon. These re-descriptions and species are important to utilizing authentic and promising candidates for biological control.

Description: How are eyes and head adapted to meet the demands of visual exploration in different tasks and environments? In two studies, we measured the horizontal movements of the eyes (using mobile eye tracking in Studies 1 and 2) and the head (using inertial sensors in Study 2) while participants completed a walking task and a search and retrieval task in a large, outdoor environment. We found that the spread of visual exploration was greater while searching compared with walking, and this was primarily driven by increased movement of the head as opposed to the eyes. The contributions of the head to gaze shifts of different eccentricities was greater when searching compared to when walking. Findings are discussed with respect to understanding visual exploration as a motor action with multiple degrees of freedom.

Description: Background We hypothesized that a decrease in frequency of controlled breaths during biphasic positive airway pressure (BIVENT), associated with an increase in spontaneous breaths, whether pressure support (PSV)-assisted or not, would mitigate lung and diaphragm damage in mild experimental acute respiratory distress syndrome (ARDS). Materials and methods Wistar rats received Escherichia coli lipopolysaccharide intratracheally. After 24 hours, animals were randomly assigned to: 1) BIVENT-100+PSV0%: airway pressure (Phigh) adjusted to VT = 6 mL/kg and frequency of controlled breaths (f) = 100 bpm; 2) BIVENT-50+PSV0%: Phigh adjusted to VT = 6 mL/kg and f = 50 bpm; 3) BIVENT-50+PSV50% (PSV set to half the Phigh reference value, i.e., PSV50%); or 4) BIVENT-50+PSV100% (PSV equal to Phigh reference value, i.e., PSV100%). Positive end-expiratory pressure (Plow) was equal to 5 cmH2O. Nonventilated animals were used for lung and diaphragm histology and molecular biology analysis. Results BIVENT-50+PSV0%, compared to BIVENT-100+PSV0%, reduced the diffuse alveolar damage (DAD) score, the expression of amphiregulin (marker of alveolar stretch) and muscle atrophy F-box (marker of diaphragm atrophy). In BIVENT-50 groups, the increase in PSV (BIVENT-50+PSV50% versus BIVENT-50+PSV100%) yielded better lung mechanics and less alveolar collapse, interstitial edema, cumulative DAD score, as well as gene expressions associated with lung inflammation, epithelial and endothelial cell damage in lung tissue, and muscle ring finger protein 1 (marker of muscle proteolysis) in diaphragm. Transpulmonary peak pressure (Ppeak,L) and pressure–time product per minute (PTPmin) at Phigh were associated with lung damage, while increased spontaneous breathing at Plow did not promote lung injury. Conclusion In the ARDS model used herein, during BIVENT, the level of PSV and the phase of the respiratory cycle in which the inspiratory effort occurs affected lung and diaphragm damage. Partitioning of inspiratory effort and transpulmonary pressure in spontaneous breaths at Plow and Phigh is required to minimize VILI.

Description: Small RNAs (sRNAs) encompass a great variety of molecules of different kinds, such as microRNAs, small interfering RNAs, Piwi-associated RNA, among others. These sRNAs have a wide range of activities, which include gene regulation, protection against virus, transposable element silencing, and have been identified as a key actor in determining the development of the cell. Small RNA sequencing is thus routinely used to assess the expression of the diversity of sRNAs, usually in the context of differentially expression, where two conditions are compared. Tools that detect differentially expressed microRNAs are numerous, because microRNAs are well documented, and the associated genes are well defined. However, tools are lacking to detect other types of sRNAs, which are less studied, and whose precursor RNA is not well characterized. We present here a new method, called srnadiff, which finds all kinds of differentially expressed sRNAs. To the extent of our knowledge, srnadiff is the first tool that detects differentially expressed sRNAs without the use of external information, such as genomic annotation or additional sequences of sRNAs.

Description: In order to eliminate COVID-19, many countries provided vaccinations. However, success depends on peoples’ knowledge levels and rates of acceptance. But, previous research on this topic is currently lacking in Bangladesh. This cross-sectional study aimed at to investigate Bangladeshi peoples’ knowledge, acceptance, and perception of challenges regarding COVID-19 vaccines. Quantitative data were collected using an online survey (n = 1975) and face-to-face interviews (n = 2200) with a pre-tested structured questionnaire. In addition, seven open-ended interviews were conducted with health experts regarding challenges of vaccination. Binary logistic regression analyses were conducted to assess the association between explanatory and dependent variables. Effect size was estimated to understand the magnitude of relationship between two variables. Of 4175 respondents, 92.6% knew about COVID-19 vaccines, while only 37.4% believed vaccines to be effective in controlling COVID-19. Nearly 46% of respondents believed that COVID-19 vaccines have side-effects, and 16.4% of respondents believed that side-effects could be life-threatening. Only 60.5% of respondents indicated that they would receive the COVID-19 vaccine. Out of 1650 respondents (39.5%) who did not intend to receive the vaccine, 948 (57.4%) believed that they would be naturally protected. Regressions results indicated that men had higher rates of knowledge regarding the vaccine. In addition, rural respondents demonstrated lower knowledge regarding the vaccine. Furthermore, education had a significant association with knowledge of COVID-19 vaccines. Respondents with university education had more knowledge regarding the vaccine (Odds ratio, OR = 29.99; 95% confidence interval, CI 11.40–78.90, effect size 1.88; p = 0.01) and correct dosage (OR 27.34; 95% CI 15.25–49.00, effect size 1.83; p = 0.01). However, women (OR 1.16; 95% CI 0.96–1.40, effect size 0.08) and rural (OR 1.24; 95% CI 1.07–1.44, effect size 0.12; p = 0.01) respondents were more enthusiastic regarding receiving the COVID-19 vaccine. Higher educated respondents showed higher probability of receiving the vaccine. Those who believed in the effectiveness of the COVID-19 vaccine were 11.57 times more interested (OR 11.57; 95% CI 8.92–15.01, effect size 1.35; p = 0.01) in receiving the vaccine. Open-ended interviews identified several challenges toward successful COVID-19 vaccination. Mass awareness creation, uninterrupted supply, equitable distribution, and sectoral coordination were suggested to achieve at least 70% immunization across the country.

Description: Replicability takes on special meaning when researching phenomena that are embedded in space and time, including phenomena distributed on the surface and near surface of the Earth. Two principles, spatial dependence and spatial heterogeneity, are generally characteristic of such phenomena. Various practices have evolved in dealing with spatial heterogeneity, including the use of place-based models. We review the rapidly emerging applications of artificial intelligence to phenomena distributed in space and time and speculate on how the principle of spatial heterogeneity might be addressed. We introduce a concept of weak replicability and discuss possible approaches to its measurement.

Description: Introduction Burnout syndrome is common among medical students, but findings about the gender differences in burnout are not consistent. The aim of this study was to assess high risk of burnout syndrome among medical students at one University in Serbia, by gender. Method A cross-sectional study was conducted at the Faculty of Medical Sciences, University of Kragujevac in 2014. The Maslach Burnout Inventory—Student Survey was used for assessment of burnout level. A questionnaire on basic socio-demographic characteristics (age, gender, marital status, habits, etc.) and academic performance (year of study, cumulative total average grade, length of study, housing, study financing, etc.) was used. The study included a total of 760 medical students (760/836 medical students; participation rate: 90.9%). Logistic regression analysis was used to determine odds ratios (OR) with 95% confidence intervals (95% CI). Results Significant gender differences were detected in prevalence of high risk of burnout syndrome (male students– 19.0% vs. female students– 12.8%, p = 0.024). A significant independent predictor of high risk for burnout syndrome in male medical students was study year (p for trend = 0.011), while in female medical students–study year (p for trend = 0.002) and use of sedatives (adjusted OR = 5.74, 95% CI = 1.96–16.77, p = 0.001). Conclusion Our results indicate the need to assess the risk of burnout syndrome at the very beginning of medical studies, in order to more effectively control the modifiable risk factors.

Description: Autosomal dominant hypophosphatemic rickets (ADHR) is an extremely rare form of genetic rickets caused by mutations in the fibroblast growth factor 23 gene. ADHR is characterized by hypophosphatemia secondary to isolated renal phosphate wasting. Only a few cases of ADHR have been reported in the literature to date. We describe the case of a 17-month-old girl who presented with severe failure to thrive (length: −4.08 standard deviation (SD), weight: −2.2 SD) and hypotonia. Hypophosphatemia, decreased tubular phosphate reabsorption (69%), and rachitic lesions were found. Genetic analysis showed the heterozygous variant c.536G〉A (NM_020638.3:c.536G〉A) in exon 3 of the FGF23 gene, leading to the diagnosis of ADHR. She was treated with phosphate salts and oral alfacalcidol. After 4 years of treatment, at 5 years of age, the patient’s ADHR resolved spontaneously. Considering the lack of knowledge regarding ADHR, we reviewed the literature to describe the features of this rare and poorly understood disease. Eleven ADHR pediatric cases have been described thus far, with cases tending to be more common in females than males. Similar to the general population, two groups of patients with ADHR can be described depending on the mutations present: patients with an R179 and R176 mutation have early-onset of disease and higher frequency of rickets, and a milder and late-onset of disease, respectively. Symptoms and disease severity may fluctuate. Spontaneous remission may occur during the pediatric age.

Description: The inability of adult mammalian cardiomyocytes to proliferate underpins the development of heart failure following myocardial injury. Although the newborn mammalian heart can spontaneously regenerate for a short period of time after birth, this ability is lost within the first week after birth in mice, partly due to increased mitochondrial reactive oxygen species (ROS) production which results in oxidative DNA damage and activation of DNA damage response. This increase in ROS levels coincides with a postnatal switch from anaerobic glycolysis to fatty acid (FA) oxidation by cardiac mitochondria. However, to date, a direct link between mitochondrial substrate utilization and oxidative DNA damage is lacking. Here, we generated ROS-sensitive fluorescent sensors targeted to different subnuclear compartments (chromatin, heterochromatin, telomeres, and nuclear lamin) in neonatal rat ventricular cardiomyocytes, which allowed us to determine the spatial localization of ROS in cardiomyocyte nuclei upon manipulation of mitochondrial respiration. Our results demonstrate that FA utilization by the mitochondria induces a significant increase in ROS detection at the chromatin level compared to other nuclear compartments. These results indicate that mitochondrial metabolic perturbations directly alter the nuclear redox status and that the chromatin appears to be particularly sensitive to the prooxidant effect of FA utilization by the mitochondria.

Description: Interactions of electronic and vibrational degrees of freedom are essential for understanding excited-states relaxation pathways of molecular systems at interfaces and surfaces. Here, we present the development of interface-specific two-dimensional electronic–vibrational sum frequency generation (2D-EVSFG) spectroscopy for electronic–vibrational couplings for excited states at interfaces and surfaces. We demonstrate this 2D-EVSFG technique by investigating photoexcited interface-active (E)-4-((4-(dihexylamino) phenyl)diazinyl)-1-methylpyridin-1- lum (AP3) molecules at the air–water interface as an example. Our 2D-EVSFG experiments show strong vibronic couplings of interfacial AP3 molecules upon photoexcitation and subsequent relaxation of a locally excited (LE) state. Time-dependent 2D-EVSFG experiments indicate that the relaxation of the LE state, S2, is strongly coupled with two high-frequency modes of 1,529.1 and 1,568.1 cm−1. Quantum chemistry calculations further verify that the strong vibronic couplings of the two vibrations promote the transition from the S2 state to the lower excited state S1. We believe that this development of 2D-EVSFG opens up an avenue of understanding excited-state dynamics related to interfaces and surfaces.

Description: Background Comorbidities are associated with increased mortality among patients receiving long-term kidney replacement therapy (KRT). However, it is not known whether primary kidney disease modifies the effect of comorbidities on KRT patients’ survival. Methods An incident cohort of all patients (n = 8696) entering chronic KRT in Finland in 2000–2017 was followed until death or end of 2017. All data were obtained from the Finnish Registry for Kidney Diseases. Information on comorbidities (coronary artery disease, peripheral vascular disease, left ventricular hypertrophy, heart failure, cerebrovascular disease, malignancy, obesity, underweight, and hypertension) was collected at the start of KRT. The main outcome measure was relative risk of death according to comorbidities analyzed in six groups of primary kidney disease: type 2 diabetes, type 1 diabetes, glomerulonephritis (GN), polycystic kidney disease (PKD), nephrosclerosis, and other or unknown diagnoses. Kaplan-Meier estimates and Cox regression were used for survival analyses. Results In the multivariable model, heart failure increased the risk of death threefold among PKD and GN patients, whereas in patients with other kidney diagnoses the increased risk was less than twofold. Obesity was associated with worse survival only among GN patients. Presence of three or more comorbidities increased the age- and sex-adjusted relative risk of death 4.5-fold in GN and PKD patients, but the increase was only 2.5-fold in patients in other diagnosis groups. Conclusions Primary kidney disease should be considered when assessing the effect of comorbidities on survival of KRT patients as it varies significantly according to type of primary kidney disease.

Description: In this study, we use molecular genetic approaches to clarify the role of the Hedgehog (Hh) pathway in regulating the blood–brain/spinal cord barrier (BBB) in the adult mouse central nervous system (CNS). Our work confirms and extends prior studies to demonstrate that astrocytes are the predominant cell type in the adult CNS that transduce Hh signaling, revealed by the expression of Gli1, a target gene of the canonical pathway that is activated in cells receiving Hh, and other key pathway transduction components. Gli1+ (Hh-responsive) astrocytes are distributed in specific regions of the CNS parenchyma, including layers 4/5/6 of the neocortex, hypothalamus, thalamus, and spinal cord, among others. Notably, although BBB properties in endothelial cells are normally regulated by both paracellular and transcellular mechanisms, conditional inactivation of Hh signaling in astrocytes results in transient, region-specific BBB defects that affect transcytosis but not paracellular diffusion. These findings stand in contrast to prior studies that implicated astrocytes as a source of Sonic hedgehog that limited extravasation via both mechanisms [J. I. Alvarez et al., Science 334, 1727–1731 (2011)]. Furthermore, using three distinct Cre driver lines as well as pharmacological approaches to inactivate Hh-pathway transduction globally in CNS astrocytes, we find that these specific BBB defects are only detected in the rostral hypothalamus and spinal cord but not the cortex or other regions where Gli1+ astrocytes are found. Together, our data show that Gli1+ Hh-responsive astrocytes have regionally distinct molecular and functional properties and that the pathway is required to maintain BBB properties in specific regions of the adult mammalian CNS.

Description: New-generation migrant workers in Chinese cities are struggling with a lack of urban resources, such as capital, skills, and relationships. To cope with the pressure of these resource constraints, new-generation migrant workers obtain urban development opportunities through resource bricolage. Based on a questionnaire survey of 365 new-generation migrant workers, we used a multiple regression analysis to study the mechanism underlying the effects of resource bricolage on the city integration of new-generation migrant workers. There were four findings: (1) resource bricolage had a significant positive effect on career growth and city integration; (2) career growth had a mediation effect on the relationship between resource bricolage and city integration; (3) environmental dynamism had a positive moderating effect on the relationship between resource bricolage and city integration for new-generation migrant workers; and (4) resource bricolage and environmental dynamism had a moderating effect on city integration through the mediation effect of career growth. The results suggest that resource bricolage promotes the career growth of new-generation migrant workers and further promotes their city integration, and that the environmental dynamism faced by workers is the external condition for promoting integration through resource bricolage. The study emphasizes the importance of resource bricolage in new-generation migrant workers’ city integration.

Description: Perceptions of the harmfulness of tobacco products may be a determinant of smoking behaviors. This study aimed to: (1) assess the perception of harmfulness of various tobacco products and e-cigarettes in Poland as well as (2) to assess the awareness of the health effects of using tobacco and e-cigarettes. A cross-sectional survey was conducted in 2019 with a nationally representative sample of 1011 individuals aged 15 and over. In the studied group, 22.3% were smokers. Smokeless tobacco was most likely to be perceived as less harmful than cigarettes (25%), followed by water pipe (24.5%), heated tobacco products (22%), e-cigarettes (21.6%), slim cigarettes (17.1%), flavored cigarettes (except menthol ones) (16.1%), menthol cigarettes (15.6%) and cigarillos (12.6%). In this study, 10% of respondents denied that smoking causes serious diseases. Most of the respondents (88.9%) were aware that smoking causes lung cancer (88.9%), but only 70.4% were aware that smoking causes stroke. Smokers compared to non-smokers were less likely to declare that smoking causes a stroke (OR: 0.43, 95%CI: 0.31–0.59; p 〈 0.001) or myocardial infarction (OR: 0.41, 95%CI: 0.29–0.60; p 〈 0.001). There were no significant differences (p 〉 0.05) in the perception of harmfulness of various tobacco products and e-cigarettes by gender, age, or occupational status.

Description: Vessel-based sonar systems that focus on the water column provide valuable information on the distribution of underwater marine organisms, but such data are expensive to collect and limited in their spatiotemporal coverage. Satellite data, however, are widely available across large regions and provide information on surface ocean conditions. If satellite data can be linked to subsurface sonar measurements, it may be possible to predict marine life over broader spatial regions with higher frequency using satellite observations. Here, we use random forest models to evaluate the potential for predicting a sonar-derived proxy for subsurface biomass as a function of satellite imagery in the California Current Ecosystem. We find that satellite data may be useful for prediction under some circumstances, but across a range of sonar frequencies and depths, overall model performance was low. Performance in spatial interpolation tasks exceeded performance in spatial and temporal extrapolation, suggesting that this approach is not yet reliable for forecasting or spatial extrapolation. We conclude with some potential limitations and extensions of this work.

Description: The area of tropical secondary forests is increasing rapidly, but data on the physical and biological structure of the canopies of these forests are limited. To obtain such data and to measure the ontogeny of canopy structure during tropical rainforest succession, we studied patch-scale (5 m2) canopy structure in three areas of 18–36 year-old secondary forest in Costa Rica, and compared the results to data from old-growth forest at the same site. All stands were sampled with a stratified random design with complete harvest from ground level to the top of the canopy from a modular portable tower. All canopies were organized into distinct high- and low-leaf-density layers (strata), and multiple strata developed quickly with increasing patch height. The relation of total Leaf Area Index (LAI, leaf area per area of ground) to patch canopy height, the existence of distinct high and low leaf- density layers (strata and free air spaces), the depth and LAI of the canopy strata and free air spaces, and the relation of the number of strata to patch canopy height were remarkably constant across the entire successional gradient. Trees were the most important contributor to LAI at all stages, while contribution of palm LAI increased through succession. We hypothesize that canopy physical structure at the patch scale is driven by light competition and discuss how this hypothesis could be tested. That canopy physical structure was relatively independent of the identity of the species present suggests that canopy physical structure may be conserved even as canopy floristics shift due to changing climate.

Description: Drowning is a leading cause of fatality among children in the United States, and pool/spa aquatic structures represent common locations of submersion incidents. This study employed narrative case review to understand characteristics related to permission, supervision, and precipitating events in childhood submersion incidents. Retroactive analysis of 1537 fatal and non-fatal submersion incidents among children age 13 years old and younger was conducted using the U.S. Consumer Products Safety Commission In-Depth Investigations dataset from 2000–2017. Narrative descriptions were coded according to the themes of permission, supervision, and precipitating events. In most (86%) incidents, the child did not have permitted water access, and 80% of narratives indicated the child was alone at time of incident. These attributes were significantly associated with a fatal outcome (No permission: OR 11.98, 95% CI 7.97–18.06; Alone: OR 34.93, 95% CI 19.69–61.96). The average length of inactive supervision time was 15.6 min; this duration significantly differed by non-fatal (3.2 min) and fatal (16.1 min) outcomes (p 〈 0.001). More than half of cases occurred under the supervision type of a parent (56%), followed by grandparents (14%) and childcare provider (10%). Submersion incidents with a non-parent supervisor were two times more likely to result in a fatal outcome (OR 1.87, 95% CI 1.07–3.64). The most frequently occurring precipitating events included outdoor play (46%), a social gathering (36%), and previous water play (15%). Narrative excerpts further illustrate how tragic submersion events can unfold quickly and unpredictably. Education campaigns should target all adults that supervise children and reiterate key findings in that many submersion incidents occur (1) without permitted pool use, (2) without active supervision, and (3) when a caregiver is distracted. Multiple strategies should be utilized to add layers of projection against submersion injury.

Description: This study classified the changes in alcohol use behavior among Korean adults and explored the related factors. The study used data from the 4th (2009) to 14th (2019) waves of the Korean Welfare Panel Study. The subjects were 8267 adults aged 19–60 years. Latent class growth analysis was used to classify the latent classes of alcohol use behavior among Korean adults, and logistic regression analysis was performed to identify the specific factors that form the classes. Additionally, the 11-year trajectories of major variables associated with alcohol use behavior for the derived classes were analyzed using growth mixture modeling. Four classes were identified according to the trajectories of alcohol use behavior. There were statistically significant differences in the trajectories of depression, self-esteem, satisfaction in family relationships, and satisfaction in leisure activities according to the class of alcohol use behavior. In particular, self-esteem and satisfaction in family relationships indicated distinctly decreasing trajectories in the low- to moderate-risk class, which suggested the need for longitudinal analysis of the factors that influence alcohol use behavior. Moreover, it is recommended that interventions for the prevention of high-risk drinking target not only individuals but also family units.

Description: Visual perception in football (“soccer” in the U.S.) is increasingly becoming a key area of interest for researchers and practitioners. This exploratory case study investigated a sub-set of visual perception, namely visual exploratory scanning. The aim of this study was to examine the scanning of four elite football midfield players in an 11 vs. 11 real-game environment using mobile eye-tracking technology. More specifically, we measured the duration and information (number of teammates and opponents) of the players’ scanning behavior. The results showed that the players’ scanning duration was influenced by the ball context and the action undertaken with the ball at the moment of scan initiation. Furthermore, fixations were found in only 2.3% of the scans. Additionally, the results revealed that the stop point is the most information-rich part of a scan and that the players had more opponents than teammates inside their video frame during scans. Practical applications and further research recommendations are presented.

Description: Digital mobility assessment using wearable sensor systems has the potential to capture walking performance in a patient’s natural environment. It enables monitoring of health status and disease progression and evaluation of interventions in real-world situations. In contrast to laboratory settings, real-world walking occurs in non-conventional environments and under unconstrained and uncontrolled conditions. Despite the general understanding, there is a lack of agreed definitions about what constitutes real-world walking, impeding the comparison and interpretation of the acquired data across systems and studies. The goal of this study was to obtain expert-based consensus on specific aspects of real-world walking and to provide respective definitions in a common terminological framework. An adapted Delphi method was used to obtain agreed definitions related to real-world walking. In an online survey, 162 participants from a panel of academic, clinical and industrial experts with experience in the field of gait analysis were asked for agreement on previously specified definitions. Descriptive statistics was used to evaluate whether consent (〉 75% agreement as defined a priori) was reached. Of 162 experts invited to participate, 51 completed all rounds (31.5% response rate). We obtained consensus on all definitions (“Walking” 〉 90%, “Purposeful” 〉 75%, “Real-world” 〉 90%, “Walking bout” 〉 80%, “Walking speed” 〉 75%, “Turning” 〉 90% agreement) after two rounds. The identification of a consented set of real-world walking definitions has important implications for the development of assessment and analysis protocols, as well as for the reporting and comparison of digital mobility outcomes across studies and systems. The definitions will serve as a common framework for implementing digital and mobile technologies for gait assessment and are an important link for the transition from supervised to unsupervised gait assessment.

Description: Introduction Hypertension (HT) is a major non-communicable disease worldwide and a growing global public health problem. Although several studies have investigated the independent associations of neck circumference (NC) and hypertension, no such studies have been conducted among the Thai population. Aim This study aims to identify risk factors associated with hypertension, which may be used to predict HT among asymptomatic adults residing in a remote rural community in central Thailand. Method 1,084 adults were included in this community-based cross-sectional study by a population-based total survey. The participants were included those who had been living in 6 villages in the rural community in the central area of Thailand. Anthropometric information, NC, body composition indexes such as waist circumference and blood pressure were measured. Logistic regression models were fitted to calculate the multi-variable adjusted prevalence and the association of NC with HT. Result The prevalence of HT among adults in the rural community was 27.7% (95% CI: 25.0–30.3). Of the 300 adults with HT, 164 participants (54.7%) were found within the unawareness HT category. We found that associated factors with HT were included larger neck circumference both continuous and categorical (≥ 37.5 in male, ≥ 32.5 in female), pre-existing diabetes mellitus, male, and higher body mass index. Conclusion Almost one-third of participants in the remote rural areas presented hypertension. NC was associated with HT independent from other risk factors. NC is a simple and useful anthropometric index to identify HT in rural Thai adults.

Description: This is a protocol of a review paper, and there is no abstract. This review is part of a doctoral project that aims to develop a discrete event simulation model to predict how many adolescents may become hypertensive in adulthood. We will use data from the Brazilian study of cardiovascular risks in adolescents, called ERICA (Portuguese acronym). This study may help promote adherence to disease prevention protocols.

Description: Mycobacterium tuberculosis (Mtb) infects one-quarter of the world’s population. Mtb and HIV coinfections enhance the comorbidity of tuberculosis (TB) and AIDS, accounting for one-third of all AIDS-associated mortalities. Humoral antibody to Mtb correlates with TB susceptibility, and engineering of Mtb antibodies may lead to new diagnostics and therapeutics. The characterization and validation of functional immunoglobulin (Ig) variable chain (IgV) sequences provide a necessary first step towards developing therapeutic antibodies against pathogens. The virulence-associated Mtb antigens SodA (Superoxide Dismutase), KatG (Catalase), PhoS1/PstS1 (regulatory factor), and GroES (heat shock protein) are potential therapeutic targets but lacked IgV sequence characterization. Putative IgV sequences were identified from the mRNA of hybridomas targeting these antigens and isotype-switched into a common immunoglobulin fragment crystallizable region (Fc region) backbone, subclass IgG2aκ. Antibodies were validated by demonstrating recombinant Ig assembly and secretion, followed by the determination of antigen-binding specificity using ELISA and immunoblot assay.

Description: The rehabilitation needs of COVID-19 survivors are increasingly recognized, with a focus on combating respiratory and neuromuscular dysfunctions. The aim here was to explore the perception of Austrian physiotherapists and physiotherapy students on post-COVID-19 rehabilitation care and to identify barriers for the application of sufficient rehabilitation. We analysed current knowledge and practical skills in respiratory physiotherapy, performing a cross-sectional national survey among physiotherapists working in outpatient settings and physiotherapy students in their last academic year of bachelor-level education in Austria. Out of 255 survey participants, one-third already had inquiries to treat post-COVID-19 patients, and the majority of respondents expected a further increased inflow of patients with rehabilitation needs (64.2%). Only 11.2% of respondents reported feeling sufficiently informed about post-COVID-19 rehabilitation. A total of 68.2% of students and up to 48.1% of physiotherapists favoured a COVID-19-specific adaptation already in the basic academic education, and 74.1% of survey participants indicated interest in attending specific training. Concerning respiratory physiotherapy, our data showed discrepancies between the estimation of the importance of specific examination and treatment techniques and the level of current experience. There is a clear lack of experience in implementing effective device-based respiratory therapy. Our data indicate an urgent need to develop new education and training programs with a focus on the interdisciplinary rehabilitation of patients with post-COVID-19 syndrome.

Description: This study’s objective was to describe the relationship between the main risk factors for oral cancer, including tobacco (in the form of cigarettes, smokeless tobacco (SLT), secondhand smoking (SS)), alcohol, and betel quid (BQ), and the occurrence of oral potentially malignant disorders (OPMDs). A community-based case-control study was conducted with a population of 1448 adults aged 40 years or above in northeastern Thailand. Patients aged 60 years or above (OR 1.79, p 〈 0.001) and female patients (OR 2.17, p 〈 0.001) had a significant chance of having OPMDs. Our multivariate analysis showed that the most potent risk factor for OPMDs occurrence was betel quid (BQ) (adjusted OR 4.65, p 〈 0.001), followed by alcohol (OR 3.40, p 〈 0.001). Even former users were at risk of developing OPMDs. The synergistic effect between these main risk factors was significantly shown in the group exposed to SLT, SS, BQ, and alcohol. The most potent synergistic effect was found in the group exposed to SLT, BQ and alcohol with the OR = 20.96.

Description: One strategy to promote physical activity (PA) is for health care providers to give exercise prescriptions (ExRx) that refer to community-based facilities. However, facilitators and barriers specific to urban programs in the US for under-resourced women are unknown. Thus the purpose of this formative research was to explore ExRx barriers and facilitators specific to US under-resourced women to inform future intervention targets and strategies. This mixed-methods community-engaged research was conducted in partnership with an urban women’s only wellness center that exchanged ExRx for free access (1–3 months). Qualitative semi-structured interviews and validated quantitative questionnaires (SF-12, International Physical Activity Questionnaire, Physical Activity Self-Efficacy, Physical Activity Stage of Change, and Barriers to Physical Activity, Social Support for Exercise, and Confusion, Hubbub, and Order Scale) were administered by phone and guided by the socio-ecological model. ExRx utilization was defined as number visits/week divided by membership duration. Means and percentages were compared between ≥1 visit/week vs.

Description: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is one of the most commonly performed transplantation procedures nowadays. Despite the significant progress made in the treatment, alloHSCT is still associated with numerous complications also affecting the oral cavity. One of them is dentin hypersensitivity (DH)—a sharp, short-term pain that occurs when stimuli act on exposed dentin. Various authors point out that DH may result in a significantly lower quality of life, among other things by impeding the consumption of food as well as causing difficulties in daily oral hygiene. The aim of the study was a preliminary analysis of the incidence rate and severity of DH pain in adult patients during late period after alloHSCT. The impact of chronic graft-versus-host disease (cGvHD) and time after alloHCT were also considered. A total of 80 patients were examined. cGvHD was identified in 52 participants. The incidence rate and severity of DH pain was assessed on the basis of a questionnaire and a clinical examination. DH pain appeared a serious problem in late period after alloHSCT regardless of post-transplant time. DH primarily affected cGvHD patients. The prevention-treatment protocol for DH should be developed for this group.

Description: Social distancing was found to prevent COVID-19 contagion. Therefore, understanding the factors associated with the public’s adherence is important. Acknowledging the importance of emotional wellbeing regarding older people’s health, and understanding their emotional state during the pandemic, are crucial. This study assessed factors associated with older people’s adherence to social distancing and their emotional status. A cross-sectional online survey was conducted among 1822 respondents above the age of 60. Distancing adherence, negative emotion, trust, social support, threat perception, attitudes, and subjective norms were assessed, and a path analysis was performed. Adherence was positively associated with attitudes (β = 0.10; p 〈 0.001), and with subjective norms (β = 0.19; p 〈 0.001). Negative emotions were positively associated with threat perception (β = 0.33; p 〈 0.001), and negatively associated with social support (β = −0.13; p 〈 0.001) and subjective norms (β = −0.10; p 〈 0.001). Attitudes mediated the relationship of threat perception (95% CI = 0.009, 0.034), trust (95% CI = 0.008, 0.029), and social support (95% CI = 0.006, 0.023) with distancing adherence. Subjective norms mediated the relationship between threat perception (95% CI = 0.014, 0.034), trust (95% CI = 0.026, 0.055), and social support (95% CI = 0.002, 0.048) with distancing adherence. Subjective norms mediated the relationship between threat perception (95% CI = −0.022, −0.006), trust (95% CI = −0.034, −0.010), and social support (95% CI = −0.029, −0.009) with negative emotions. When promoting social distancing adherence, subjective norms and attitudes must be considered, as they play a role in promoting adherence and negative-emotion regulation.

Description: With excellent creep resistance, good high-temperature microstructural stability and good irradiation resistance, oxide dispersion strengthened (ODS) alloys are a class of important alloys that are promising for high-temperature applications. However, plagued by a nerve-wracking fact that the oxide particles tend to aggregate at grain boundary of metal matrix, their improvement effect on the mechanical properties of metal matrix tends to be limited. In this work, we employ a unique in-house synthesized oxide@W core-shell nanopowder as precursor to prepare W-based ODS alloy. After low-temperature sintering and high-energy-rate forging, high-density oxide nanoparticles are dispersed homogeneously within W grains in the prepared alloy, accompanying with the intergranular oxide particles completely disappearing. As a result, our prepared alloy achieves a great enhancement of strength and ductility at room temperature. Our strategy using core-shell powder as precursor to prepare high-performance ODS alloy has potential to be applied to other dispersion-strengthened alloy systems.

Description: The widespread UbiD enzyme family utilises the prFMN cofactor to achieve reversible decarboxylation of acrylic and (hetero)aromatic compounds. The reaction with acrylic compounds based on reversible 1,3-dipolar cycloaddition between substrate and prFMN occurs within the confines of the active site. In contrast, during aromatic acid decarboxylation, substantial rearrangement of the substrate aromatic moiety associated with covalent catalysis presents a molecular dynamic challenge. Here we determine the crystal structures of the multi-subunit vanillic acid decarboxylase VdcCD. We demonstrate that the small VdcD subunit acts as an allosteric activator of the UbiD-like VdcC. Comparison of distinct VdcCD structures reveals domain motion of the prFMN-binding domain directly affects active site architecture. Docking of substrate and prFMN-adduct species reveals active site reorganisation coupled to domain motion supports rearrangement of the substrate aromatic moiety. Together with kinetic solvent viscosity effects, this establishes prFMN covalent catalysis of aromatic (de)carboxylation is afforded by UbiD dynamics.

Description: Melanoma cells rely on developmental programs during tumor initiation and progression. Here we show that the embryonic stem cell (ESC) factor Sall4 is re-expressed in the Tyr::NrasQ61K; Cdkn2a−/− melanoma model and that its expression is necessary for primary melanoma formation. Surprisingly, while Sall4 loss prevents tumor formation, it promotes micrometastases to distant organs in this melanoma-prone mouse model. Transcriptional profiling and in vitro assays using human melanoma cells demonstrate that SALL4 loss induces a phenotype switch and the acquisition of an invasive phenotype. We show that SALL4 negatively regulates invasiveness through interaction with the histone deacetylase (HDAC) 2 and direct co-binding to a set of invasiveness genes. Consequently, SALL4 knock down, as well as HDAC inhibition, promote the expression of an invasive signature, while inhibition of histone acetylation partially reverts the invasiveness program induced by SALL4 loss. Thus, SALL4 appears to regulate phenotype switching in melanoma through an HDAC2-mediated mechanism.

Description: β cells may participate and contribute to their own demise during Type 1 diabetes (T1D). Here we report a role of their expression of Tet2 in regulating immune killing. Tet2 is induced in murine and human β cells with inflammation but its expression is reduced in surviving β cells. Tet2-KO mice that receive WT bone marrow transplants develop insulitis but not diabetes and islet infiltrates do not eliminate β cells even though immune cells from the mice can transfer diabetes to NOD/scid recipients. Tet2-KO recipients are protected from transfer of disease by diabetogenic immune cells.Tet2-KO β cells show reduced expression of IFNγ-induced inflammatory genes that are needed to activate diabetogenic T cells. Here we show that Tet2 regulates pathologic interactions between β cells and immune cells and controls damaging inflammatory pathways. Our data suggests that eliminating TET2 in β cells may reduce activating pathologic immune cells and killing of β cells.

Description: Ghrelin, also called “the hunger hormone”, is a gastric peptide hormone that regulates food intake, body weight, as well as taste sensation, reward, cognition, learning and memory. One unique feature of ghrelin is its acylation, primarily with an octanoic acid, which is essential for its binding and activation of the ghrelin receptor, a G protein-coupled receptor. The multifaceted roles of ghrelin make ghrelin receptor a highly attractive drug target for growth retardation, obesity, and metabolic disorders. Here we present two cryo-electron microscopy structures of Gq-coupled ghrelin receptor bound to ghrelin and a synthetic agonist, GHRP-6. Analysis of these two structures reveals a unique binding pocket for the octanoyl group, which guides the correct positioning of the peptide to initiate the receptor activation. Together with mutational and functional data, our structures define the rules for recognition of the acylated peptide hormone and activation of ghrelin receptor, and provide structural templates to facilitate drug design targeting ghrelin receptor.

Description: Evidence suggests that non-binary people have poorer mental and physical health outcomes, compared with people who identify within the gender binomial (man/woman). Research on the impact of the COVID-19 pandemic on mental health has been conducted worldwide in the last few months. It has however overlooked gender diversity. The aim of our study was to explore social and health-related factors associated with mental health (anxiety and depression) among people who do not identify with the man/woman binomial during COVID-19 lockdown in Spain. A cross-sectional study with online survey, aimed at the population residing in Spain during lockdown, was conducted. Data were collected between the 8th of April until the 28th of May 2020, the time period when lockdown was implemented in Spain. Mental health was measured using the Generalised Anxiety Disorder 7-item (GAD-7) scale for anxiety, and the Patient Health Questionnaire (PHQ-9) for depression. The survey included the question: Which sex do you identify with? The options “Man”, “Woman”, “Non-binary” and “I do not identify” were given. People who answered one of the last two options were selected for this study. Multivariate regression logistic models were constructed to evaluate the associations between sociodemographic, social and health-related factors, anxiety and depression. Out of the 7125 people who participated in the survey, 72 (1%) identified as non-binary or to not identify with another category. People who do not identify with the man/woman binomial (non-binary/I do not identify) presented high proportions of anxiety (41.7%) and depression (30.6%). Poorer mental health was associated with social-employment variables (e.g., not working before the pandemic) and health-related variables (e.g., poor or regular self-rated health). These findings suggest that social inequities, already experienced by non-binary communities before the pandemic, may deepen due to the COVID-19 pandemic.

Description: In everyday life, we group and subdivide time to understand the sensory environment surrounding us. Organizing time in units, such as diurnal rhythms, phrases, and beat patterns, is fundamental to behavior, speech, and music. When listening to music, our perceptual system extracts and nests rhythmic regularities to create a hierarchical metrical structure that enables us to predict the timing of the next events. Foot tapping and head bobbing to musical rhythms are observable evidence of this process. In the special case of polyrhythms, at least two metrical structures compete to become the reference for these temporal regularities, rendering several possible beats with which we can synchronize our movements. While there is general agreement that tempo, pitch, and loudness influence beat perception in polyrhythms, we focused on the yet neglected influence of beat subdivisions, i.e., the least common denominator of a polyrhythm ratio. In three online experiments, 300 participants listened to a range of polyrhythms and tapped their index fingers in time with the perceived beat. The polyrhythms consisted of two simultaneously presented isochronous pulse trains with different ratios (2:3, 2:5, 3:4, 3:5, 4:5, 5:6) and different tempi. For ratios 2:3 and 3:4, we additionally manipulated the pitch of the pulse trains. Results showed a highly robust influence of subdivision grouping on beat perception. This was manifested as a propensity towards beats that are subdivided into two or four equally spaced units, as opposed to beats with three or more complex groupings of subdivisions. Additionally, lower pitched pulse trains were more often perceived as the beat. Our findings suggest that subdivisions, not beats, are the basic unit of beat perception, and that the principle underlying the binary grouping of subdivisions reflects a propensity towards simplicity. This preference for simple grouping is widely applicable to human perception and cognition of time.

Description: Objectives Eradicated infectious diseases like smallpox can re-emerge through accident or the designs of bioterrorists, and cause heavy casualties. Presently, the populace is largely susceptible as only a small percentage is vaccinated, and their immunity is likely to have waned. And when the disease re-emerges, the susceptible individuals may be manipulated by disinformation on Social Media to refuse vaccines. Thus, a combination of countermeasures consisting of antiviral drugs and vaccines and a range of policies for their application need to be investigated. Opinions regarding whether to receive vaccines evolve over time through social exchanges via networks that overlap with but are not identical to the disease propagation networks. These couple the spread of the biological and information contagion and necessitate a joint investigation of the two. Methods We develop a computationally tractable metapopulation epidemiological model that captures the joint spatio-temporal evolution of an infectious disease (e.g., smallpox, COVID-19) and opinion dynamics. Results Considering smallpox, the computations based on the model show that opinion dynamics have a substantial impact on the fatality count. Towards understanding how perpetrators are likely to seed the infection, we identify a) the initial distribution of infected individuals that maximize the overall fatality count; and b) which habitation structures are more vulnerable to outbreaks. We assess the relative efficacy of different countermeasures and conclude that a combination of vaccines and drugs minimize the fatalities, and by itself, drugs reduce fatalities more than the vaccine. Accordingly, we assess the impact of increase in the supply of drugs and identify the most effective among a collection of policies for administering of drugs for various parameter combinations. Many of the observed patterns are stable to variations of a diverse set of parameters. Conclusions Our findings provide a quantitative foundation for various important elements of public health discourse that have largely been conducted qualitatively.

Description: Introduction Improving hypertension management is a national priority that can decrease morbidity and mortality. Evidence-based hypertension management guidelines advocate self-measured BP (SMBP), but widespread implementation of SMBP is lacking. The purpose of this study was to describe the perspective of primary care physicians (PCPs) on SMBP to identify the barriers and facilitators for implementing SMBP. Methods We collected data from PCPs from a large health system using semi-structured interviews based on the Theoretical Domains Framework (TDF). Responses were recorded, transcribed, and qualitatively analyzed into three overarching TDF domains based on the Behavior Change Wheel (BCW): 1) Motivation 2) Opportunity and 3) Capabilities. The sample size was based on theme saturation. Results All 17 participating PCPs believed that SMBP is a useful, but underutilized tool. Although individual practices varied, most physicians felt that the increased data points from SMBP allowed for better hypertension management. Most felt that overcoming existing barriers would be difficult, but identified several facilitators: physician support of SMBP, the possibility of having other trained health professionals to assist with SMBP and patient education; improving patient engagement and empowerment with SMBP, and the interest of the health system in using technology to improve hypertension management. Conclusion PCPs believe that SMBP can improve hypertension management. There are numerous barriers and facilitators for implementing SMBP. Successful implementation in clinical practice will require implementation strategies targeted at increasing patient acceptability and reducing physician workload. This may need a radical change in the current methods of managing hypertension.

Description: Background The mid-life emergence of higher levels of total cholesterol (TC) for women than for men has been observed in different Western and Asian populations. The aim of this study was to investigate whether there is evidence of this in Vietnam and, if so, whether it can be explained by ageing, by body size and fatness, or by socio-demographic characteristics and behavioural factors. Methods Participants (n = 14706, 50.9% females) aged 25–64 years were selected by multi-stage stratified cluster sampling from eight provinces each representing one of the eight geographical regions of Vietnam. Measurements were made using the World Health Organization STEPS protocols. Linear regression was used to assess the independent contributions of potential explanatory factors to mean levels of TC. Data were analysed using complex survey methods. Results Men and women had similar mean levels of body mass index (BMI), and men had modestly higher mean levels of waist circumference (WC), in each 5-year age category. The mean TC of women increased more or less continuously across the age range but with a step-up at age 50 years to reach higher concentrations on average than those of their male counterparts. The estimated step-up was not eliminated by adjustment for anthropometric indices including BMI or WC, or by adjustment for socio-demographic characteristics or behavioural factors. The estimated step-up was least for women with the greatest weight. Conclusion There is a marked step-up in TC at age 50 years for Vietnamese women that cannot be explained by their age, or by their body fatness or its distribution, or by their socio-demographic characteristics or behavioural factors, and which results in greater mean levels of TC for middle-aged women than for their male counterparts in Vietnam.