Antagonist peptides (ANTs) of vasoactive intestinal polypeptide receptors (VIP-Rs) are shown to enhance T cell activation and proliferation in vitro, as well as improving T cell-dependent anti-tumor response in acute myeloid leukemia (AML) murine models. However, peptide therapeutics often suffer from poor metabolic stability and exhibit a short half-life/fast elimination in vivo. In this study, we describe efforts to enhance the drug properties of ANTs via chemical modifications. The lead antagonist (ANT308) is derivatized with the following modifications: N-terminus acetylation, peptide stapling, and PEGylation. Acetylated ANT308 exhibits diminished T cell activation in vitro, indicating that N-terminus conservation is critical for antagonist activity. The replacement of residues 13 and 17 with cysteine to accommodate a chemical staple results in diminished survival using the modified peptide to treat mice with AML. However, the incorporation of the constraint increases survival and reduces tumor burden relative to its unstapled counterpart. Notably, PEGylation has a significant positive effect, with fewer doses of PEGylated ANT308 needed to achieve comparable overall survival and tumor burden in leukemic mice dosed with the parenteral ANT308 peptide, suggesting that polyethylene glycol (PEG) incorporation enhances longevity, and thus the antagonist activity of ANT308. Full article

Olfactory neuroblastoma (ONB) is an uncommon neuroendocrine malignancy arising from the olfactory neuroepithelium. ONB frequently presents with nonspecific sinonasal complaints, including nasal obstruction and epistaxis, and diagnosis can be obtained through a combination of physical examination, nasal endoscopy, and computed tomography and magnetic resonance imaging. Endoscopic resection with negative margins, with or without craniotomy, as necessary, is the standard of care for definitive treatment of ONB. Regional metastasis to the neck is often detected at presentation or may occur in a delayed fashion and should be addressed through elective neck dissection or radiation. Adjuvant radiotherapy should be considered, particularly in the case of high grade or tumor stage, as well as positive surgical margins. Systemic therapy is an area of active investigation in both the neoadjuvant and adjuvant setting, with many advocating in favor of induction chemotherapy for significant orbital or intracranial involvement prior to surgical resection. Various targeted immunotherapies are currently being studied for the treatment of recurrent or metastatic ONB. Prolonged locoregional and distant surveillance are indicated following definitive treatment, given the tendency for delayed recurrence and metastasis. Full article

This review explores the historical development of cardiology knowledge, from ancient Egyptian psychostasis to the modern comprehension of cardiac neuromodulation. In ancient Egyptian religion, psychostasis was the ceremony in which the deceased was judged before gaining access to the afterlife. This ritual was also known as the “weighing of the heart” or “weighing of the soul.” The Egyptians believed that the heart, not the brain, was the seat of human wisdom, emotions, and memory. They were the first to recognize the cardiocentric nature of the body, identifying the heart as the center of the circulatory system. Aristotle (fourth century BC) considered the importance of the heart in human physiology in his philosophical analyses. For Galen (third century AD), the heart muscle was the site of the vital spirit, which regulated body temperature. Cardiology knowledge advanced significantly in the 15th century, coinciding with Leonardo da Vinci and Vesalius’s pioneering anatomical and physiological studies. It was William Harvey, in the 17th century, who introduced the concept of cardiac circulation. Servet’s research and Marcello Malpighi’s discovery of arterioles and capillaries provided a more detailed understanding of circulation. Richard Lower emerged as the foremost pioneer of experimental cardiology in the late 17th century. He demonstrated the heart’s neural control by tying off the vagus nerve. In 1753, Albrecht von Haller, a professor at Göttingen, was the first to discover the heart’s automaticity and the excitation of muscle fibers. Towards the end of the 18th century, Antonio Scarpa challenged the theories of Albrecht von Haller and Johann Bernhard Jacob Behrends, who maintained that the myocardium possessed its own “irritability”, on which the heartbeat depended, and was independent of neuronal sensitivity. Instead, Scarpa argued that the heart required innervation to maintain life, refuting Galenic notions. In contemporary times, the study of cardiac innervation has regained prominence, particularly in understanding the post-acute sequelae of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection (PASC), which frequently involves cardiorespiratory symptoms and dysregulation of the intrinsic cardiac innervation. Recently, it has been recognized that post-acute sequelae of acute respiratory infections (ARIs) due to other pathogens can also be a cause of long-term vegetative and somatic symptoms. Understanding cardiac innervation and modulation can help to recognize and treat long COVID and long non-COVID-19 (coronavirus disease 2019) ARIs. This analysis explores the historical foundations of cardiac neuromodulation and its contemporary relevance. By focusing on this concept, we aim to bridge the gap between historical understanding and modern applications. This will illuminate the complex interplay between cardiac function, neural modulation, cardiovascular health, and disease management in the context of long-term cardiorespiratory symptoms and dysregulation of intrinsic cardiac innervations. Full article

Background: The reproducibility of radiomics features extracted from CT and MRI examinations depends on several physiological and technical factors. The aim was to evaluate the impact of contrast agent timing on the stability of radiomics features using dynamic contrast-enhanced perfusion CT (dceCT) or MRI (dceMRI) in prostate and lung cancers. Methods: Radiomics features were extracted from dceCT or dceMRI images in patients with biopsy-proven peripheral prostate cancer (pzPC) or biopsy-proven non-small cell lung cancer (NSCLC), respectively. Features that showed significant differences between contrast phases were identified using linear mixed models. An L2-penalized logistic regression classifier was used to predict class labels for pzPC and unaffected prostate regions-of-interest (ROIs). Results: Nine pzPC and 28 NSCLC patients, who were imaged with dceCT and/or dceMRI, were included in this study. After normalizing for individual enhancement patterns by defining seven individual phases based on a reference vessel, 19, 467 and 128 out of 1204 CT features showed significant temporal dynamics in healthy prostate parenchyma, prostate tumors and lung tumors, respectively. CT radiomics-based classification accuracy of healthy and tumor ROIs was highly dependent on contrast agent phase. For dceMRI, 899 and 1027 out of 1118 features were significantly dependent on time after contrast agent injection for prostate and lung tumors. Conclusions: CT and MRI radiomics features in both prostate and lung tumors are significantly affected by interindividual differences in contrast agent dynamics. Full article

Binary mixtures of active pharmaceutical ingredients (API) are researched to improve the oral bioavailability of pharmaceutical dosage forms. The purpose of this study was to obtain mixtures of meloxicam and L-tartaric acid because tartaric acid improves intestinal absorption and meloxicam is more soluble in a weakly basic environment. The mixtures in the 0–1 molar fraction range, obtained from solvent-assisted mechanosynthesis, were investigated by differential scanning calorimetry (DSC), Fourier Transform Infrared (FTIR) spectroscopy, Fourier Transform Raman spectroscopy (FT-Raman), X-ray powder diffraction (XRD) and solubility tests. The physicochemical characteristics of the compounds obtained from DSC data reveal, for the first time, the formation of a co-crystal at meloxicam molar fraction of 0.5. FTIR spectroscopy data show the existence of hydrogen bonds between the co-crystal components meloxicam and L-tartaric acid. FT-Raman spectroscopy was used complementary with FT-IR spectroscopy to analyze the pure APIs and their mixtures, to emphasize the appearance/disappearance and the shifts of the position/intensity of vibrational bands, following the formation of hydrogen-bonded structures or van der Waals interactions, and to especially monitor the crystal lattice vibrations below 400 cm⁻¹. The experimental results obtained by X-ray powder diffraction confirmed the formation of the co-crystal by the loss and, respectively, the apparition of peaks from the single components in the co-crystal diffractogram. The solubility tests showed that the co-crystal product has a lower aqueous solubility due to the acidic character of the other component, tartaric acid. However, when the solubility tests were performed in buffer solution of pH 7.4, the solubility of meloxicam from the co-crystal mixture was increased by 57% compared to that of pure meloxicam. In conclusion, the studied API mixtures may be considered potential biomaterials for improved drug release molecular solids. Full article

Previously, we reported that epidermal growth factor-like module-containing mucin-like hormone receptor-like 1 (EMR1/ADGRE1) is abnormally expressed in colon cancer (CC) and is a risk factor for lymph node metastasis (LNM) and poor recurrence-free survival in patients with abundant tumor-associated macrophages (TAMs). However, the signaling pathways associated with EMR1 expression in CC progression remain unclear. In this study, we aimed to explore the role of EMR1 and its signaling interactions with macrophages in CC progression. Spatial transcriptomics of pT3 microsatellite unstable CC tissues revealed heightened Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling in EMR1-HL CC with LNM compared to EMR1-N CC without LNM. Through in vitro coculture of CC cells with macrophages, EMR1 expression by CC cells was found to be induced by TAMs, ultimately interacting with upregulated JAK/STAT signaling, increasing cell proliferation, migration, and motility, and reducing apoptosis. JAK2/STAT3 inhibition decreased the levels of EMR1, JAK2, STAT1, and STAT3, significantly impeded the proliferation, migration, and mobility of cells, and increased the apoptosis of EMR1⁺ CC cells compared to their EMR1^KO counterparts. Overall, TAMs-induced EMR1 upregulation in CC cells may promote LNM and CC progression via JAK2/STAT1,3 signaling upregulation. This study provides further insights into the molecular mechanisms involving macrophages and intracellular EMR1 expression in CC progression, suggesting its clinical significance and offering potential interventions to enhance patient outcomes. Full article

The use of artificial lighting in a total or supplementary way is a current trend, with growing interest due to the increase in the global population and climate change, which require high-yield, quality, and fast-growing crops with less water and a smaller carbon footprint. This experiment aimed to evaluate the effect of light-emitting diode (LED) lighting on the production of basil, mustard, and red cabbage seedlings under controlled artificial conditions and in a greenhouse as a supplementary lighting regime. Under controlled conditions, the experiment was conducted with basil seedlings, comparing LED light with two wavelengths (purple and white light). In a greenhouse, mustard and red cabbage seedlings were evaluated under natural light (regular photoperiod) and with supplementary purple lighting of 3 h added to the photoperiod. The variables assessed were aerial fresh mass (AFM), aerial dry mass (ADM), root dry mass (RDM), plant length (PL), and leaf area (LA). Basil seedlings grown under purple light showed greater length and AFM than those grown under white light, with no effect on the production of secondary metabolites. In the greenhouse experiment, red cabbage seedlings showed an increase in AFM, ADM, and DRM with light supplementation, with no effect on LA. AFM showed no statistical difference in mustard seedlings, but the productive parameters LA, ADM, and DRM were higher with supplementation. None of the evaluated treatments influenced the production of phenolic compounds and flavonoids in the three species evaluated. Light supplementation affected red cabbage and mustard seedlings differently, promoting better development in some production parameters without affecting the production of phenolic compounds and flavonoids in either plant. Thus, light supplementation or artificial lighting can be considered a tool to enhance and accelerate the growth of seedlings, increasing productivity and maintaining the quality of the secondary metabolites evaluated. Thus, this technology can reduce operational costs, enable cultivation in periods of low natural light and photoperiod, and cultivate tropical species in temperate environments in completely artificial (indoor) conditions. Full article

This study aimed to review recent developments in the agri-food industry, focusing on the integration of innovative digital systems into the livestock industry. Over the last 50 years, the production of animal-based foods has increased significantly due to the rising demand for meat. As a result, farms have increased their livestock numbers to meet consumer demand, which has exacerbated challenges related to environmental sustainability, human health, and animal welfare. In response to these challenges, precision livestock farming (PLF) technologies have emerged as a promising solution for sustainable livestock production. PLF technologies offer farmers the opportunity to increase efficiency while mitigating environmental impact, securing livelihoods, and promoting animal health and welfare. However, the adoption of PLF technologies poses several challenges for farmers and raises animal welfare concerns. Additionally, the existing legal framework for the use of PLF technologies is discussed. In summary, further research is needed to advance the scientific understanding of PLF technologies, and stakeholders, including researchers, policymakers, and funders, need to prioritize ethical considerations related to their implementation. Full article

The non-destructive study of soil micromorphology via computed tomography (CT) imaging has yielded significant insights into the three-dimensional configuration of soil pores. Precise pore analysis is contingent on the accurate transformation of CT images into binary image representations. Notably, segmentation of 2D CT images frequently harbors inaccuracies. This paper introduces a novel three-dimensional pore segmentation method, BDULSTM, which integrates U-Net with convolutional long short-term memory (CLSTM) networks to harness sequence data from CT images and enhance the precision of pore segmentation. The BDULSTM method employs an encoder–decoder framework to holistically extract image features, utilizing skip connections to further refine the segmentation accuracy of soil structure. Specifically, the CLSTM component, critical for analyzing sequential information in soil CT images, is strategically positioned at the juncture of the encoder and decoder within the U-shaped network architecture. The validation of our method confirms its efficacy in advancing the accuracy of soil pore segmentation beyond that of previous deep learning techniques, such as U-Net and CLSTM independently. Indeed, BDULSTM exhibits superior segmentation capabilities across a diverse array of soil conditions. In summary, BDULSTM represents a state-of-the-art artificial intelligence technology for the 3D segmentation of soil pores and offers a promising tool for analyzing pore structure and soil quality. Full article

The need for sustainable development in the context of pesticide use has been recognized by the European Union. The “Farm to Fork Strategy” indicates a goal of 50% reduction in pesticide use by 2030. To address this challenge, we used the concept of ionic liquids to modify known resistance inducers, i.e., a group of substances whose action is indicated as an alternative to fungicides. A new, patented substance developed by us, which is a choline 3,5-dichlorosalicylate, has been tested in the context of its use in sugar beet cultivation with the aim of controlling Cercospora leaf spot (CLS). The results suggest that the use of this substance in combination with one fungicide treatment reduces disease infection and produces yields very similar to the use of a standard protection program assuming the use of two fungicides. Such results provide the basis for further development of 3,5-dichlorosalicylate in terms of its use in agriculture. Thanks to its use, it was possible to resign from one fungicide treatment, while maintaining protection against CLS and yields at the same level as for the full fungicide protection program. Such an approach is in line with European Union policies. Full article

Synchrophasor data contain a trove of information on the power system and its dynamics. These measurements have a high potential to unlock our ability to cope with changing system conditions and challenges posed by distributed and intermittent energy sources. While Phasor Measurement Units (PMUs) have seen a large deployment in the grid, their applications are limited by the software platforms that are deployed in control centers to monitor the grid. In this paper, we present an open source toolkit that enables fast prototyping of PMU applications. The toolkit is akin to a software development kit (SDK) for synchrophasor applications, providing a number of functionalities that enable high-level PMU application development within the LabVIEW environment. This Smart-grid Synchrophasor SDK (S3DK) proposes a paradigm based on the concept of distributed applications, which allows development and deployment to be independent of the existing software stack deployed in control centers and to leverage PMU data at any level of a synchrophasor system hierarchy. This paper serves to introduce the S3DK, which is released as open source software to facilitate broader and fast prototyping of synchrophasor applications. Full article

Research has shown that mental disorders in working-age individuals are associated with a significant burden of disability, sickness absence, and presenteeism, resulting in lost productivity. This study aims to assess the impact of depressive disorders on the labour markets in the European Union countries, with a particular focus on the disparities between the ‘old’ and ‘new’ EU countries. The study analysed the process of convergence of the burden of depressive disorders among people aged 20–54 in the group of EU-27 countries in the years 1990–2019, using data from the Global Burden of Disease Study 2019. The initial hypothesis of persistent inequalities in the system studied was verified. The study measured years lived with disability (YLD) due to depressive disorders in the working-age population. The analysis revealed that depressive disorders have a significant impact on the highly developed economies of the EU-14 countries. The convergence assessment did not confirm the effect of catching up with more favourable economies over time, and the inequalities observed at the beginning of the analysis period worsened. This study’s results expand upon the existing literature on the consequences of depressive disorders by introducing the perspective of inequalities in the studied area. These inequalities were observed between EU-27 economies with varying levels of socio-economic development. Full article

This paper presents a design study focusing on the thermal safety of an induction motor integrated with a pump unit, which operates submerged in liquefied natural gas (LNG) in the LNG tanks of LNG carrier ships ranging from 150 K to 200 K cubic meters (CBM). In this study, we carried out the electromagnetic design of the induction motor and verified the thermal safety against a temperature increase due to losses during the motor operation through thermal fluid analysis, taking into account the discharge flow of the emergency pump and the air gap of the motor. In the electromagnetic design, the resistivity of the stator winding copper conductors and the rotor aluminum bars, which act as important design constants for the rated operating and starting characteristics of the induction motor in cryogenic temperature environments, reflects the characteristic of linearly changing with the temperature. In cryogenic environments, the reduction in the resistance of the rotor bars of the induction motor leads to a decrease in the starting torque characteristics. Therefore, the shape optimization design of the rotor bar was performed to improve the starting torque characteristics, and 2D electromagnetic analysis was performed on the magnetic flux density distribution and magnetic saturation using Ansys Electromagnetics 16.0. After the electromagnetic design, a 3D thermal flow analysis was conducted using Ansys Fluent 17.0, considering the stator iron losses, rotor bar losses, stator and rotor iron losses, and stray load losses as heat sources. The flow analysis aimed to analytically verify the thermal safety concerning the vaporization of the LNG flowing through the emergency pump’s discharge flow path and the motor’s internal air gap. The motor was manufactured, and the rated and starting operating characteristics of the motor were measured under LN2 submerged conditions according to the IEEE 112 F1 method, to validate whether the performance characteristics met the specifications’ requirements. Subsequently, the thermal safety of the motor was finally verified through a temperature increase test under LNG submerged conditions after assembling it with the emergency pump. Full article

Aim. The sulfhydryl (thiols) group of glutathione plays an important role in the neutralization of foreign organic compounds and the reduction in peroxides. The purpose of the study is to evaluate the concentration of sulfhydryl groups in the gingival tissue of healthy individuals and those with gingivitis or periodontitis, and to examine the differences between these groups. Material and methods. To assess the concentration of sulfhydryl groups (thiols) in the gingival tissue of healthy individuals and those with gingivitis or periodontitis, we used spectrophotometric analysis using dithionitrobenzoate (DTNB) as a reagent to measure the accessible sulfhydryl groups present in gingival tissue proteins. The sample was divided into three distinct groups: individuals with periodontal health, gingivitis, and periodontitis, and different indices were used to assess the periodontal status of the participants. Next, a statistical analysis was conducted to compare the concentrations of sulfhydryl groups among the different groups of patients. Conclusions. The results of this study showed significantly decreased levels of sulfhydryl (thiols) groups in gingival tissue from patients with gingivitis and periodontitis, compared with healthy people (control group). These results confirm the role of sulfhydryl (thiols) groups in defense against free radicals. They share a significant role in detoxification, signal transduction, apoptosis, and various other functions at the molecular level. Full article

In response to the transformative impact of digital technology on education, this study introduces a novel performance management framework for virtual learning environments suitable for the metaverse era. Based on the Structural Equation Modeling (SEM) approach, this paper proposes a comprehensive evaluative model, anchored on the integration of the Theory of Planned Behavior (TPB), the Unified Theory of Acceptance and Use of Technology (UTAUT), and the Community of Inquiry Framework (CoI). The model synthesizes five Key Performance Indicators (KPIs)—content delivery, student engagement, metaverse tool utilization, student performance, and adaptability—to intricately assess academic avatar performances in virtual educational settings. This theoretical approach marks a significant stride in understanding and enhancing avatar efficacy in the metaverse environment. It enriches the discourse on performance management in digital education and sets a foundation for future empirical studies. As virtual online environments gain prominence in education and training, this research study establishes the basic principles and highlights the key points for further empirical research in the new era of the metaverse educational environment. Full article

Many countries around the world are rapidly advancing sustainable development (SD) through the exploitation of clean energy sources such as solar and wind energy, which are becoming the core of the sustainable energy transition. In recent years, the continuous advancement of Earth system models (ESMs) has facilitated numerous studies utilizing them to predict long-term and large-scale meteorological elements, consequently enabling forecasts of wind and solar energy. These forecasts provide critical guidance for formulating national renewable energy policies. Nevertheless, the current literature on ESMs predicting wind and solar energy lacks sufficient integration. Hence, to comprehend the focal points and future research prospects, we conducted this systematic review, employing four academic search tools to comprehensively analyze the relevant literature from the past five years. We summarized the general analytical process and compared the content and conclusions of the literature. The study reveals that future photovoltaic (PV) potential for electricity generation may increase in certain regions but decrease in others, while the global potential for concentrated solar power (CSP) may diminish, influenced by diverse factors and displaying significant regional disparities. In addition, wind resource trends vary in different regions, and forecasts exhibit considerable uncertainty. Therefore, many studies have corrected wind speeds prior to predicting wind energy. Subsequent research endeavors should concentrate on optimizing ESMs, investigating the impacts of technological innovation, and enhancing the prediction and analysis of extreme weather events. Full article

Trichotillomania (TTM) is a psychiatric disorder involving chronic, recurrent urges to pull out one’s own hair, arising frequently in childhood and early adolescence. This disorder predominantly affects women and has a high co-morbidity with many other psychiatric conditions. Currently, the etiology is unknown, which makes treating TTM extremely difficult. While the epidemiology and proposed causes will be discussed briefly, the primary purpose of this review is to provide a comprehensive, updated summary of the psychological and pharmacological management options for patients diagnosed with TTM, as new clinical trial data for previously studied and novel treatments have become available within the last decade. Of the behavioral interventions, cognitive behavioral therapy (CBT) and habit reversal training (HRT) have demonstrated the greatest improvements in hair-pulling severity, with HRT showing the most efficacy for long-term maintenance of progress. Pharmacological therapies with the most success include Olanzapine, Clomipramine, and N-Acetylcysteine, though larger replication studies are needed. Selective serotonin reuptake inhibitors (SSRIs) have yielded inconsistent results in clinical trials, yet they are frequently prescribed for TTM. Naltrexone, Dronabinol, and Inositol are emerging as potential treatments, but the results suggest that additional studies are needed. Future research directions include larger placebo-controlled pharmacological trials, exploring the efficacy of combined behavioral and pharmacological approaches compared to monotherapy, and delving into the potential genetic and neurochemical contributions that may underlie TTM. Full article

Background: Signet ring cell adenocarcinoma (SRCC) of the bladder is a rare and aggressive histological subtype of bladder cancer. Due to its infrequency, the understanding of its clinical behaviour, treatment strategies, and outcomes remains limited, being primarily derived from isolated case reports and series. Objective: To systematically review and analyse the available literature on SRCC of the bladder, emphasizing its clinical characteristics, diagnostic approaches, treatment modalities, and outcomes. Material and Methods: A comprehensive search was conducted across PubMed, Embase, and Medline following the PRISMA guidelines, including case reports, case series, observational studies, and clinical trials reporting on bladder SRCC. Results: We included 38 articles reporting on 77 patients, primarily males (79.2%), with a median age of 64 years. The most common presenting symptoms were haematuria (64.8%) and lower urinary tract symptoms (46.3%). All the diagnoses were based on histopathological examination of bladder tissue samples and immunohistochemistry. Mixed histological types of bladder cancer were found in 20.7% of cases, most commonly urothelial carcinoma (61.1%). The treatments varied, with 53.2% of patients undergoing radical cystectomy, 24.7% receiving radiotherapy, and 16.9% receiving chemotherapy. The five-year survival rates were 9.4%. Conclusion: Bladder SRCC presents aggressively, with varied treatment strategies; however, radical cystectomy appears to be the optimal means of surgical management for organ-confined disease. The overall survival rate is low, highlighting the need for further research to understand and manage this rare bladder cancer variant. All patients should undergo evaluation to exclude extravesical primaries. This systematic review contributes to a better understanding of this disease and may guide clinical management strategies. Full article

Objectives: Few studies have examined the role of prostate MRI in patients with suspicious digital rectal examination (DRE) and/or PSA > 10 ng/mL. In a cohort of non-screened patients with suspicious DRE, we investigated the rate of avoidable prostate biopsies and potentially missed clinically significant prostate cancer (csPCa) with negative MRI, and the concordance between targeted biopsy (TBx) and systematic biopsy (SBx) in detecting csPCa with positive MRI. Methods: We retrospectively examined 199 biopsy-naïve patients with suspicious DRE who underwent prostate MRI before transperineal biopsy. Prostate Imaging—Reporting and Data System (PI-RADS) v2.1 ≥ 3 category of the index lesion defined a positive MRI. Combined TBx/SBx and SBx alone were performed for positive and negative MRI, respectively. An International Society of Urogenital Pathology Grade Group ≥ 2 defined csPCa. We calculated the csPCa detection rate of TBx, SBx, and combined TBx/SBx. The Cohen kappa statistic was used to measure the concordance between TBx and SBx. Results: Ninety-one (45.7%) csPCa cases were detected. MRI was positive in 153 (76.9%) patients. In the 46 patients with negative MRI, SBx detected 5 (10.9%) csPCa cases. Prostate biopsy could, thus, be avoided in 41/199 (20.6%) patients at the cost of missing 5/91 (5.5%) csPCa cases. The concordance between TBx and SBx in detecting csPCa with positive mpMRI was substantial (k = 0.70). Specifically, 6/86 (6.9%) csPCa cases were detected with TBx, and 17/86 (19.7%) with SBx alone. Concordance was almost perfect (k = 0.82) in patients with PSA > 10 ng/mL. Only 4/38 (10.5%) csPCa cases were missed by TBx, and only 1 (2.6%) csPCa case was identified by TBx alone. Conclusions: MRI in patients with suspicious DRE could avoid roughly 21% of unnecessary biopsies at the cost of missing approximately 6% of csPCa cases. Moreover, MRI and TBx complemented SBx in detecting csPCa in the subgroup with PSA > 10 ng/mL. Full article

Objectives: Our objective was to assess the rate of complications and gastrointestinal adverse effects of rectal spacer insertion for salvage post prostatectomy radiation therapy. Methods: A retrospective observational study was performed. Between September 2018 and March 2022, 64 post-radical prostatectomy patients who were planned for salvage radiation therapy received a rectal spacer. The selected patients were those who had nerve-sparing prostatectomy with intrafascial or interfascial dissections (where Denonvillier’s fascia is retained). Radiation dose to the rectal wall and gastrointestinal symptoms were assessed. Symptoms were graded using the National Cancer Center Institute Common Terminology Criteria for Adverse Events v4.0 grading scheme. A total of 39 patients had pre-spacer planning computer tomography (CT) scans, and the rectal dose before and after the spacer insertion was calculated. Comparisons were made using the Student’s t-test, with a p-value < 0.05 representing statistical significance. Finally, clinicians were surveyed to rate the ease of the procedure using a 5-point Likert scale of 1 to 5 (1: very difficult, 2: difficult, 3: moderate, 4: easy, 5: very easy). Results: A total of 64 patients successfully underwent rectal spacer insertion. The mean age was 64.4 years (standard deviation: 5.7 years). After a median of 14 months’ (range 6 to 35) follow up, acute grade 1 and above gastrointestinal (GI) toxicities were seen in 28% of patients (grade 2 in 1.5%), and late grade 1 and above GI toxicities were seen in 12% of patients (grade 2 in 1.5%). Amongst the 39 patients with pre-spacer planning CT images, the volume of the rectum receiving 60%, 70%, 80%, 90%, and 100% of the prescribed radiation dose was reduced by 25.9%, 34.2%, 35.4%, 43.7%, and 61.7%, respectively. All dose reductions were statistically significant. The procedure was rated as “easy” or “very easy” to perform in 56% of cases. Conclusions: The insertion of a rectal spacer in selected patients undergoing PPRT is feasible and safe and significantly improves rectal wall radiation dosimetry in salvage post prostatectomy radiation therapy. It was accomplished in >95% of patients, increasing vesico-rectal separation from ‘immediate vicinity’ to 11 mm without any post-operative complications in experienced hands. In addition, it achieved significant reduction in rectal radiation doses, leading to low rates of acute and late grade 2 toxicity. Full article

Introduction: Health technology assessment (HTA) agencies express a clear preference for randomized controlled trials when assessing the comparative efficacy of two or more treatments. However, an indirect treatment comparison (ITC) is often necessary where a direct comparison is unavailable or, in some cases, not possible. Numerous ITC techniques are described in the literature. A systematic literature review (SLR) was conducted to identify all the relevant literature on existing ITC techniques, provide a comprehensive description of each technique and evaluate their strengths and limitations from an HTA perspective in order to develop guidance on the most appropriate method to use in different scenarios. Methods: Electronic database searches of Embase and PubMed, as well as grey literature searches, were conducted on 15 November 2021. Eligible articles were peer-reviewed papers that specifically described the methods used for different ITC techniques and were written in English. The review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: A total of 73 articles were included in the SLR, reporting on seven different ITC techniques. All reported techniques were forms of adjusted ITC. Network meta-analysis (NMA) was the most frequently described technique (in 79.5% of the included articles), followed by matching-adjusted indirect comparison (MAIC) (30.1%), network meta-regression (24.7%), the Bucher method (23.3%), simulated treatment comparison (STC) (21.9%), propensity score matching (4.1%) and inverse probability of treatment weighting (4.1%). The appropriate choice of ITC technique is critical and should be based on the feasibility of a connected network, the evidence of heterogeneity between and within studies, the overall number of relevant studies and the availability of individual patient-level data (IPD). MAIC and STC were found to be common techniques in the case of single-arm studies, which are increasingly being conducted in oncology and rare diseases, whilst the Bucher method and NMA provide suitable options where no IPD is available. Conclusion: ITCs can provide alternative evidence where direct comparative evidence may be missing. ITCs are currently considered by HTA agencies on a case-by-case basis; however, their acceptability remains low. Clearer international consensus and guidance on the methods to use for different ITC techniques is needed to improve the quality of ITCs submitted to HTA agencies. ITC techniques continue to evolve quickly, and more efficient techniques may become available in the future. Full article

Soybean is a high-value food source, and the invasive weeds Mexican prickly poppy (Argemone ochroleuca) could release allelochemicals that inhibit the growth of this crop. The impact of A. ochroleuca on the germination and growth of soybean is not well documented. Therefore, the aim of this study was to evaluate the TLC profiles of different extracts of A. ochroleuca and assess the effects of extracts on the germination of soybean seeds. Shoots and roots of A. ochroleuca were weighed and 100 g of each was separately extracted with 1000 mL deionized water, hexane or acetone. Ten concentrations of water extracts ranging from 10 to 100 mL per 100 mL of deionized water and three concentrations of acetone and hexane extracts ranging from 2.5 to 7.5 g/L were separately used for seed germination bioassays. Thin-layer chromatography (TLC) analysis was used to compare the chemical profiles in the shoot and root water, and in the hexane and acetone extracts of A. ochroleuca. The highest reduction was recorded from the water extract, at 100%. The TLC profiling of A. ochroleuca addressed different classes of compounds, including alkaloids, phenolic acids and flavanoids. There is, however, a need to identify the most active phytochemicals in the suppression of germination. Full article