Miracle-dz/UniFAR-FTUs huggingface dataset:
Simultaneous of in a

16 Trichloroethylene (TCE) is a human carcinogen that is commonly found in landfill leachate. 17 Contaminated leachate plumes may be intercepted prior to reaching groundwater and treated 18 in situ using permeable reactive barriers (PRB). This study used a packed column system 19 containing herbal pomace and spruce biochar, previously shown to have TCE adsorptive 20 capabilities. Influent containing raw or autoclaved landfill leachate was used to investigate 21 the potential for environmental micro-organisms to establish a TCE-dechlorinating biofilm on 22 the biochar, in order to prolong the operational life span of the system. TCE removal ≥ 99.7 23 % was observed by both biochars. No dichloroethylene (DCE) isomers were present in the 24 column effluents, but cis -1,2 DCE was adsorbed to the biochar treating raw landfill leachate, indicating that dechlorination was occurring biologically in these columns. Known microbial 1 species that are individually capable of complete dechlorination of TCE to ethene were not 2 detected by 16S rRNA gene sequencing, but several species capable of partial TCE 3 dechlorination ( Desulfitobacterium spp., Sulfurospirillium spp. and Desulfuromonas spp) 4 were present in the biofilms of the columns treating raw landfill leachate. These data 5 demonstrate that biochar from waste material may be capable of supporting a dechlorinating 6 biofilm to promote bioremediation of TCE. 7
GlomerulonephritisImmune-Mediated Anti-Podocyte Deposits in a Mouse Model of Nephrotic Syndrome and Subepithelial

Subepithelial immune complex deposition in glomerular disease causes local inﬂammation and proteinuria by podocyte disruption. A rat model of membranous nephropathy, the passive Heymann nephritis, suggests that Abs against speciﬁc podocyte Ags cause subepithelial deposit formation and podocyte foot process disruption. In this study, we present a mouse model in which a polyclonal sheep anti-mouse podocyte Ab caused subepithelial immune complex formation. Mice developed a nephrotic syndrome with severe edema, proteinuria, hypoalbuminemia, and elevated cholesterol and triglycerides. Development of proteinuria was biphasic: an initial protein loss was followed by a second massive increase of protein loss beginning at approximately day 10. By histology, podocytes were swollen. Electron microscopy revealed 60–80% podocyte foot process effacement and subepithelial deposits, but no disruption of the glomerular basement membrane. Nephrin and synaptopodin staining was severely disrupted, and podocyte number was reduced in anti-podocyte serum-treated mice, indicating severe podocyte damage. Immunohistochemistry detected the injected anti-podocyte Ab exclusively along the glomerular ﬁltration barrier. Immunoelectron microscopy localized the Ab to podocyte foot processes and the glomerular basement membrane. Similarly, immunohistochemistry localized mouse IgG to the subepithelial space. The third complement component (C3) was detected in a linear staining pattern along the glomerular basement membrane and in the mesangial hinge region. However, C3-deﬁcient mice were not protected from podocyte damage, indicating a complement-independent mechanism. Twenty proteins were identiﬁed as possible Ags to the sheep anti-podocyte serum by mass spectrometry. Together, these data establish a reproducible model of immune-mediated podocyte injury in mice with subepithelial immune complex formation. The
The role of PET in the management of sarcoidosis

Purpose of review PET has emerged as method to determine the location and extent of disease activity in sarcoidosis. As most clinicians do not routinely utilize PET in the management of sarcoidosis, an understanding of the imaging technique is needed to comprehend the impact that PET abnormalities have on diagnosis, prognosis, and treatment. Recent findings Although PET can detect inflammation because of sarcoidosis throughout the body, it is most often utilized for the diagnosis of cardiac sarcoidosis for which it may provide information about prognosis and adverse events. Whenever PET is combined with cardiac magnetic resonance (CMR), clinicians may be able to increase the diagnostic yield of imaging. Furthermore, PET abnormalities have the potential to be utilized in the reduction or augmentation of therapy based on an individual's response to treatment. Although various biomarkers are used to monitor disease activity in sarcoidosis, an established and reproducible relationship between PET and biomarkers does not exist. Summary PET has the potential to improve the diagnosis of sarcoidosis and alter treatment decisions but prospective trials are needed to define the role of PET while also standardizing the performance and interpretation of the imaging modality.
Impact of COVID‐19 on student attainment and pedagogical needs when undertaking independent scientific research

Research is often an essential component of completing a veterinary medicine degree, with universities worldwide aiming to teach students a variety of techniques and general research comprehension and skills. As universities worldwide navigated the COVID‐19 pandemic, it was often necessary to move towards distance learning, this was employed for the research module at The University of Nottingham, School of Veterinary Medicine and Science. Following completion of their independent research project, each student cohort was sent a student evaluation of the module questionnaire and quantitative and qualitative analysis was undertaken. In addition, assessment outcomes based on dissertation grade, supervisor grade and overall module score were analysed quantitatively. This was conducted on both the individual cohorts and between the pre‐ and peri‐pandemic groups, ranging from 2017–2018 through to 2021–2022 cohorts. The students received increased dissertation and supervisor grades (by nearly 6%) during the 2021–2022 peri‐pandemic cohort, when compared to the pre‐pandemic cohorts, but did differ significantly compared to the 2020–2021 cohort. The pre‐ and peri‐pandemic Likert‐scale ratings for module organisation and assessment criteria were similar, workload management and the ability to explore concepts and ideas was reduced in the peri‐pandemic cohorts, whereas the accessibility to resources was increased in the peri‐pandemic students compared to those taught prior to the pandemic. Student feedback can provide essential information when designing and managing research projects and when compared to assessment grades it can help us understand attainment, essential information when providing a quality university level education whilst supporting student welfare following the COVID‐19 pandemic.
Heterogeneity in Alcohol-Related Severity and Interests in Going to Treatment in Community Adults with Alcohol Use Disorder (AUD)

Abstract Rationale Alcohol use disorder (AUD) is highly prevalent among adults in the US and is associated with substantial personal and societal costs. Yet only a small percentage of adults with AUD initiate treatment, including those with severe AUD symptoms who are most in need of treatment. In this paper we use latent profile analysis (LPA) to describe differences in symptoms of AUD severity and alcohol-related consequences among untreated adults with severe AUD symptoms who were recruited from the community. Identification of such differences will result in better understanding of this population and will improve methods of treatment outreach. Method The LPAs were conducted on the baseline data of 403 (50% male, 77% White, M age = 40.74 with severe AUD recruited from the community and enrolled in a trial of an intervention designed to encourage treatment initiation. Participants reported no prior AUD treatment history. The LPAs were based on indicators of AUD severity, alcohol-related negative consequences, and self-reported intention to initiate AUD treatment. Results The LPAs revealed 4 profiles. Profile membership was predicted by baseline participant sex and whether they were living with a partner and was associated with baseline past 30-days alcohol consumption. Conclusions The findings characterize and describe the variability among adults in the community with untreated severe AUD on variables that tend to motivate such individuals to seek treatment, which could significantly advance treatment outreach efforts.
A mechanism of self-lipid endocytosis mediated by the receptor Mincle

Significance Dysregulation of lipid endocytosis, a normal physiological process of cellular lipid uptake, often underlies the pathogenesis of some widespread diseases such as atherosclerosis, obesity, and diabetes. However, the mechanisms of lipid endocytosis are incompletely understood, and only a few such mechanisms have been discovered, limiting the available therapeutic strategies and targets in these diseases. Here we found that the receptor Mincle, previously known as a pattern recognition receptor of the innate immune system, plays a significant role in endocytosis. The results have revealed a fundamental pathway of lipid endocytosis, which we call Mincle-mediated endocytosis.
Identifying infected patients using semi-supervised and transfer learning

OBJECTIVES Early identification of infection improves outcomes, but developing models for early identification requires determining infection status with manual chart review, limiting sample size. Therefore, we aimed to compare semi-supervised and transfer learning algorithms with algorithms based solely on manual chart review for identifying infection in hospitalized patients. MATERIALS AND METHODS This multicenter retrospective study of admissions to 6 hospitals included "gold-standard" labels of infection from manual chart review and "silver-standard" labels from nonchart-reviewed patients using the Sepsis-3 infection criteria based on antibiotic and culture orders. "Gold-standard" labeled admissions were randomly allocated to training (70%) and testing (30%) datasets. Using patient characteristics, vital signs, and laboratory data from the first 24 hours of admission, we derived deep learning and non-deep learning models using transfer learning and semi-supervised methods. Performance was compared in the gold-standard test set using discrimination and calibration metrics. RESULTS The study comprised 432 965 admissions, of which 2724 underwent chart review. In the test set, deep learning and non-deep learning approaches had similar discrimination (area under the receiver operating characteristic curve of 0.82). Semi-supervised and transfer learning approaches did not improve discrimination over models fit using only silver- or gold-standard data. Transfer learning had the best calibration (unreliability index P value: .997, Brier score: 0.173), followed by self-learning gradient boosted machine (P value: .67, Brier score: 0.170). DISCUSSION Deep learning and non-deep learning models performed similarly for identifying infection, as did models developed using Sepsis-3 and manual chart review labels. CONCLUSION In a multicenter study of almost 3000 chart-reviewed patients, semi-supervised and transfer learning models showed similar performance for model discrimination as baseline XGBoost, while transfer learning improved calibration.
Multiple dimeric structures and strand-swap dimerization of E-cadherin in solution visualized by high-speed atomic force microscopy

Significance E-cadherin is a major cell–cell adhesion molecule that connects opposing cells via extracellular domains (ectodomains) and regulates tissue morphology and dynamics. Mutual binding of the ectodomains has been considered to be formed by a strand-swap (SS-) dimer via an X-dimer; however, the dimerization processes have not been directly visualized, and other potential dynamic interactions have been proposed. In this study, high-speed atomic force microscopy (HS-AFM), mutational analyses, and structural modeling revealed the dimeric structures that are mainly classified into SS- (W-shaped), X-like (cross-shaped), and S-shaped (or reverse S-shaped) dimers. The structural transition from the S-shaped and X-like dimers to the SS-dimer formation, visualized by HS-AFM, suggests the contribution of dynamic interactions to the SS-dimer formation of E-cadherin in solution.
Clinical Validation of Genome Reference Consortium Human Build 38 in a Laboratory Utilizing Next-Generation Sequencing Technologies.

BACKGROUND Laboratories utilizing next-generation sequencing align sequence data to a standardized human reference genome (HRG). Several updated versions, or builds, have been released since the original HRG in 2001, including the Genome Reference Consortium Human Build 38 (GRCh38) in 2013. However, most clinical laboratories still use GRCh37, which was released in 2009. We report our laboratory's clinical validation of GRCh38. METHODS Migration to GRCh38 was validated by comparing the coordinates (lifting over) of 9443 internally curated variants from GRCh37 to GRCh38, globally comparing protein coding sequence variants aligned with GRCh37 vs GRCh38 from 917 exomes, assessing genes with known discrepancies, comparing coverage differences, and establishing the analytic sensitivity and specificity of variant detection using Genome in a Bottle data. RESULTS Eight discrepancies, due to strand swap or reference base, were observed. Three clinically relevant variants had the GRCh37 alternate allele as the reference allele in GRCh38. A comparison of 88 295 calls between builds identified 8 disease-associated genes with sequence differences: ABO, BNC2, KIZ, NEFL, NR2E3, PTPRQ, SHANK2, and SRD5A2. Discrepancies in coding regions in GRCh37 were resolved in GRCh38. CONCLUSIONS There were a small number of clinically significant changes between the 2 genome builds. GRCh38 provided improved detection of nucleotide changes due to the resolution of discrepancies present in GRCh37. Implementation of GRCh38 results in more accurate and consistent reporting.
Linking Depression with Negative Alcohol-Related Consequences: A Structural Equation Model Among a Clinically Depressed Population

Abstract Background and Objectives: Previous research suggests that rumination acts as a mediating mechanism in the association between depression and drinking motives, particularly drinking to cope, as well as negative alcohol-related consequences. In this study, we tested the connections between depressive symptoms, rumination, drinking motives, alcohol consumption, and alcohol-related problems in a clinically depressed population (N = 209). Methods: Structural equation modeling was used to test the models. Specifications were based on the results of a previously evaluated model in a sample of college students. Results: The complex model showed a significant positive association between depressive symptoms and rumination. Drinking motives (enhancement and coping) were linked to more negative alcohol-related consequences. In a simplified model, pronounced depressive symptoms were associated with both increased ruminative thinking and more negative alcohol-related problems. Rumination was connected with stronger drinking motives (combined in one general factor), which were again associated with alcohol consumption and alcohol-related problems. Limitations: The use of self-report measures to determine diagnostic validity. Conclusions: In a clinically depressed sample, depressive symptoms were linked to increased negative alcohol-related consequences. This association was partially explained by rumination and drinking motives. However, rumination was less relevant than previous studies suggested.
PBPK modelling to predict drug-biologic interactions with cytokine modulators: Are these relevant and is IL-6 enough?


Drugs that modulate cytokine levels are often used for the treatment of cancer as well as inflammatory or immunological disorders. Pharmacokinetic drug-biologic interactions (DBI) may arise from suppression or elevation of cytochrome P450 (CYP) enzymes caused by the increase or decrease in cytokine levels following administration of these therapies. There is in vitro and in vivo evidence that demonstrates a clear link between raised interleukin (IL)-6 levels and CYP suppression, in particular CYP3A4. However despite this, the changes in IL-6 levels in vivo rarely lead to significant drug interactions (AUC and Cmax ratios < 2-fold). The clinical significance of such interactions therefore remains questionable and is dependent on the therapeutic index of the small molecule therapy. Physiologically-based pharmacokinetic (PBPK) modelling has been used successfully to predict the impact of raised IL-6 on CYP activities. Beyond IL-6, published data show little evidence that IL-8, IL-10, and IL-17 suppress CYP enzymes. I n vitro data suggest that IL-1β, IL-2, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ can cause suppression of CYP enzymes. Despite in vivo there being a link between IL-6 levels and CYP suppression, the evidence to support a direct effect of IL-2, IL-8, IL-10, IL-17, IFN-γ, TNF-α or vascular endothelial growth factor (VEGF) on CYP activity is inconclusive. This commentary will discuss the relevance of such drug-biologic interactions and whether current PBPK models considering only IL-6 are sufficient. Significance Statement This commentary summarizes the current in vitro and in vivo literature regarding cytokine-mediated CYP suppression and compares the relative suppressive potential of different cytokines in reference to IL-6. It also discusses the relevance of drug-biologic interactions to therapeutic use of small molecule drugs and whether current PBPK models considering only IL-6 are sufficient to predict the extent of drug-biologic interactions.
Impulsivity and Perpetration of Intimate Partner Aggression: The Moderating Effects of Negative Affective State and Alcohol

Abstract Background: The goal of this study was to test the interactive effects of negative urgency, state negative affect, and alcohol intoxication on intimate partner aggression (IPA) perpetration. Methods: Heavy drinkers who recently perpetrated IPA completed self-report measures of impulsivity, were administered an alcohol or control beverage, and completed a laboratory aggression task. State negative affect was assessed unobtrusively via the Facial Action Coding System. Results: Consistent with our prediction, negative urgency was significantly and positively related to IPA when state negative affect was also high, but this relation was not significant when state negative affect was low. Conclusions: These results have implications for understanding the role of negative affect and impulsivity in IPA perpetration and for understanding trait models of impulsivity in general.
Multiple insecticide resistance and first evidence of V410L kdr mutation in Aedes (Stegomyia) aegypti (Linnaeus) from Burkina Faso

The response to recent dengue outbreaks in Burkina Faso was insecticide‐based, despite poor knowledge of the vector population's susceptibility to the insecticides used. Here, we report on the susceptibility to the main insecticide classes and identify important underlying mechanisms in Aedes aegypti populations in Ouagadougou and Banfora, in 2019 and 2020. Wild Ae. aegypti were tested as adults in WHO bioassays and then screened in real time melting curve qPCR analyses to genotype the F1534C, V1016I, and V410L Aedes kdr mutations. Ae. aegypti showed moderate resistance to 0.1% bendiocarb (80–95% survival post‐exposure), 0.8% Malathion (60–100%), 0.21% pirimiphos‐methyl (75% – 97%), and high resistance to 0.03% deltamethrin (20–70%). PBO pre‐exposure partially restored pyrethroid susceptibility. Genotyping detected high frequency of 1534C allele (0.92) and moderate 1016I (0.1–0.32). The V410L mutation was detected in Burkina Faso for the first time (frequency 0.1–0.36). Mosquitoes surviving 4 h exposure to 0.03% deltamethrin had significantly higher frequencies of the F1534C mutation than dead mosquitoes (0.70 vs. 0.96, p < 0.0001) and mosquitoes surviving 2 ‐ 4 h exposure had a significantly reduced life span. Ae. aegypti from Burkina Faso are resistant to multiple insecticide classes with multiple mechanisms involved, demonstrating the essential role of insecticide resistance monitoring within national dengue control programmes.
Impact of immobilized algae and its consortium in biodegradation of the textile dyes

Abstract In biological engineering, cell immobilization is a modern technique for immobilizing free cells in a small space. Disintegration and elimination of azo dyes [Reactive Orange 122 (orange 2RL) and Reactive Red 194 (Reactive Red M-2BF)] were investigated by using Chlorococcum sp. and Chlorococcum sp. mixed with Scenedesmus obliquus, respectively. After 7 days of incubation, the maximum decolorization was spotted at 40 ppm for Reactive Orange 122 and 20 ppm for Reactive Red 194 by Chlorococcum sp. and Chlorococcum sp. mixed with S. obliquus, respectively. The findings revealed that the best decolorization activity was found at pH 11 and 25 °C under aeration conditions. BG11 was considered the best medium for azo dye decolorization with a high decolorization percentage. Additionally, different concentrations of nitrogen and phosphorus show the high activity of decolorization of both dyes. Referring to vitamins (thiamin and Ascorbic acid), all studied concentrations showed high decolorization activity with immobilized Chlorococcum sp. mixed with S. obliquus; however, different concentrations (20, 40, and 60 mg/l) of thiamin showed completely decolorization of Reactive Red 194 after 3 days, and 60 mg/l of ascorbic acid showed completely decolorization of Reactive Orange 122 after 5 days of inoculation. FT-IR and GC-Ms analysis for azo dyes after and before treatment with Immobilization of Chlorococcum sp. and Chlorococcum sp. mixed with Scenedesmus obliquus were detected. Novelty statement: The natural carrier algae and its consortium combined with a suitable immobilization technique were considered in this study, which is non-toxic, enhanced their bioremediation potential for dyes, and allowed multiple uses of biocatalysts. The novel use of the immobilization and its consortium of algae on the degradation efficiency of azo dyes and studying the effect of physicochemical conditions on decolorization and degradation of azo dyes. Application of immobilization techniques using microalgae could be excellent bioremediation of wastewaters.
National surveillance of cancer survival in Iran (IRANCANSURV): Analysis of data of 15 cancer sites from nine population‐based cancer registries

Cancer survival is a key indicator for the national cancer control programs. However, survival data in the East Mediterranean region (EMR) are limited. We designed a national cancer survival study based on population‐based cancer registries (PBCRs) from nine provinces in Iran. The current study reports 5‐year net survival of 15 cancers in Iranian adults (15‐99 years) during 2014 to 2015 in nine provinces of Iran. We used data linkages between the cancer registries and the causes of death registry and vital statistics and active follow‐up approaches to ascertain the vital status of the patients. Five‐year net survival was estimated through the relative survival analysis. We applied the international cancer survival standard weights for age standardization. Five‐year survival was highest for prostate cancer (74.9%, 95% CI 73.0, 76.8), followed by breast (74.4%, 95% CI 72.50, 76.3), bladder (70.4%, 95% CI 69.0, 71.8) and cervix (65.2%, 95% CI 60.5, 69.6). Survival was below 25% for cancers of the pancreas, lung, liver, stomach and esophagus. Iranian cancer patients experience a relatively poor prognosis as compared to those in high‐income countries. Implementation of early detection programs and improving the quality of care are required to improve the cancer survival among Iranian patients. Further studies are needed to monitor the outcomes of cancer patients in Iran and other EMR countries.