bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilizing Technology to Enhance the Ecological Validity of Cognitive and Functional Assessments in Schizophrenia: An Overview of the State-of-the-Art
Authors: Horan William P , Moore Raeanne C , Belanger Heather G , Harvey Philip D 
Published: November 2024

Abstract
Cognitive impairment is a core feature of schizophrenia and a key determinant of functional outcome. Although conventional paper-and-pencil based cognitive assessments used in schizophrenia remained relatively static during most of the 20th century, this century has witnessed the emergence of innovative digital technologies that aim to enhance the ecological validity of performance-based assessments. This narrative review provides an overview of new technologies that show promise for enhancing the ecological validity of cognitive and functional assessments. We focus on 2 approaches that are particularly relevant for schizophrenia research: (1) digital functional capacity tasks, which use simulations to measure performance of important daily life activities (e.g., virtual shopping tasks), delivered both in-person and remotely, and (2) remote device-based assessments, which include self-administered cognitive tasks (e.g., processing speed test) or functionally-focused surveys regarding momentary activities and experiences (e.g., location, social context), as well as passive sensor-based metrics (e.g., actigraphy measures of activity), during daily life. For each approach, we describe the potential for enhancing ecological validity, provide examples of select measures that have been used in schizophrenia research, summarize available data on their feasibility and validity, and consider remaining challenges. Rapidly growing evidence indicates that digital technologies have the potential to enhance the ecological validity of cognitive and functional outcome assessments, and thereby advance research into the causes of, and treatments for, functional disability in schizophrenia.
Assessing Gender Diversity in American Society for Dermatologic Surgery Fellowship Leadership: A 2013 to 2022 Trend Analysis
Authors: Richmond Alexandra , Aristizabal Miguel , Greywal Tanya , Gregoski Mathew J. , Almukhtar Rawaa 
Published: November 2024

BACKGROUND
While there has been improved gender representation in dermatology, there remains areas for improvement, especially in leadership positions. Studies have evaluated diversity in various dermatology subspecialties, but evaluation of gender diversity in cosmetic dermatology is lacking.

OBJECTIVE
To evaluate the temporal trends in gender diversity within the American Society for Dermatologic Surgery (ASDS) Cosmetic Dermatologic Surgery Fellowship Programs from 2013 to 2022. To discuss strategies for improvement.

MATERIALS AND METHODS
The ASDS Cosmetic Dermatologic Surgery Fellowship program directors and fellows were reviewed from 2013 to 2022. Gender was determined through online professional websites and biographies. The number and proportion of each gender was determined for each year, and the change over time was calculated.

RESULTS
The number of fellowship positions and program directors has increased from 2013 to 2022. Most of the fellows have been women. The average yearly rate of change for fellows is +1.67 and +0.67 for men and women. Most of the fellowship directors have been men. The average yearly rate of change is +1.56 and +0.44 for men and women.

CONCLUSION
Gender inequalities remain across leadership positions and further studies are necessary to better determine why these discrepancies exist and how to improve this inequality.
A Review of Best Practices for Gender-Affirming Laser Hair Removal
Authors: Yanes Daniel A. , Smith Payton , Avram Mathew M. 
Published: November 2024

BACKGROUND
Permanent hair reduction is an integral part of gender-affirming medical care, especially for transgender patients undergoing surgeries such as phalloplasty and vaginoplasty. Hair removal helps reduce complications and alleviate gender dysphoria associated with unwanted facial and body hair.

OBJECTIVE
To examine the methods, efficacy, and access issues of hair removal in transgender patients, with a focus on its role in surgical preparation and gender dysphoria reduction.

MATERIALS AND METHODS
A literature review was conducted to analyze the effectiveness of laser hair removal (LHR) and electrolysis for permanent hair reduction. The review also explored regional regulatory barriers and insurance coverage limitations affecting access to these services.

RESULTS
Laser hair removal and electrolysis are both effective for hair removal, with LHR being less painful and faster. Laser hair removal is often preferred but requires multiple treatments and proper laser settings. Insurance coverage remains inconsistent, limiting access to these procedures. Postoperative hair regrowth in neovaginal or neourethral sites can be managed with hormonal adjustments and further treatments.

CONCLUSION
Hair removal plays an essential role in reducing surgical complications and gender dysphoria in transgender patients. A multidisciplinary approach between dermatologists and surgeons is essential, and addressing regulatory and access barriers is critical for equitable care.
TENORM Regulation in the United States of America post-West Virginia vs. EPA
Authors: Lynn Spenser , Wilson Charles , Caffrey Emily 
Published: November 2024

Abstract
The regulation of technologically enhanced naturally occurring radioactive materials (TENORM) in the United States of America consists of fragmentary rules split between the federal and state governments. The US Environmental Protection Agency (EPA) has recognized the complex nature of TENORM regulation but has not issued explicit TENORM rules at the federal level. Some states have enacted their own TENORM statutes and regulations to fill this gap, while others claim the authority to regulate TENORM under their general radiation protection regulations. The Supreme Court of the United States (SCOTUS) ruling in West Virginia vs. EPA created a new lens through which environmental regulations should be viewed and may have implications for the regulation of TENORM. This paper presents an overview of West Virginia vs. EPA, the major questions doctrine on which SCOTUS based its opinion, and how it might apply to TENORM regulations at the federal and state levels. Two states, one with explicit TENORM regulations and another with only general radiation protection statutes, are considered in the context of a hypothetical legal challenge to TENORM regulations. The role and impact of West Virginia vs. EPA in administrative law is still to be determined, but it does prompt an opportunity to conduct a new, more thorough review of TENORM regulation at the federal and state level.
Complications in Pelvic Organ Prolapse With 3-Month Versus 6-Month Pessary Care: Pilot Study
Authors: Giorgenon Geovana Volta , Galhardo Letícia Martineli , de Araujo Camila Carvalho , de Castro Edilson Benedito , Brito Luiz Gustavo Oliveira , Juliato Cássia Raquel Teatin 
Published: November 2024

Importance
Despite evidence emphasizing the necessity of routine care for women with pelvic organ prolapse (POP) using pessaries, the frequency of follow-up is unclear.

Objective
The aim of this study was to compare the presence of complications in women with POP using vaginal pessaries with cleaning and gynecological examination every 3 or 6 months.

Study Design
This pilot study was a randomized clinical trial of women with advanced POP using a ring pessary. The women were randomized into 2 groups (“3-month group” and a “6-month group”) that returned for evaluation by a health care professional that monitored the vagina, removed the pessary, cleaned it, and reinserted it. Sociodemographic and clinical data were collected. During their follow-up, the women answered a questionnaire regarding the presence of vaginal symptoms and had a physical examination and vaginal sampling for microbiological analysis.

Results
A total of 38 women were randomized into 2 groups: the 3-month group (n = 18) and the 6-month group (n = 20). Baseline characteristics of the groups were similar except for age, which was 70.7 (±7.4) years in the 3-month group and 74.7 (±6.6) years in the 6-month group (P = 0.022). Regarding physical examination, after 12 months of follow-up, 4 women in each group presented erosions or ulcers in each group, but without difference (P = 1). The presence of bacterial vaginosis was more frequent in the group with cleaning every 6 months (P = 0.026).

Conclusions
The prevalence of ulcerations was similar in both groups with cleaning every 3 or 6 months, but the group with cleaning every 6 months showed a higher prevalence of bacterial vaginosis.
Biofilm and Its Characteristics in Venous Ulcers
Authors: Frison Susiane Sucasas , Borges Eline Lima , Guedes Antônio Carlos Martins , Honorato-Sampaio Kinulpe 
Published: November 2024

PURPOSE
The aim of the study was to analyze the characteristics of the biofilm of venous ulcers in terms of location and formation and to relate the presence of the biofilm to ulcer characteristics including duration, injured area, and necrotic tissue.

DESIGN
Descriptive clinical study.

MATERIALS AND METHODS
We obtained 2 biopsy fragments (tissue samples) from 44 patients with venous ulcers treated at a public outpatient clinic in a university hospital in Belo Horizonte, Brazil. Ulcers were photographed and classified according to the duration. In addition, the wound size and proportion of wound surface covered by necrotic tissue were measured. One fragment from each ulcer underwent microbiological analysis, while the other was analyzed using transmission electron microscopy. Data analysis was limited to fragments from patients with bacteria in the microbiological analysis.

RESULTS
Data analysis is based on samples obtained from 21 ulcers in 21 patients who had bacteria in their ulcer based on microbiologic analysis of a tissue sample. Most ulcers were open for 2 to 10 years, 57% (n = 12) were 16 cm2 or smaller, and the proportion of the wound bed covered by necrotic tissue coverage varied widely. Of the 21/44 patients (48%) with bacteria in their ulcers, only 3 patients had bacterial biofilm present in the transmission electron microscopy, corresponding to 7% of the 44 patients. Pseudomonas aeruginosa was the most frequent bacterium, identified in 10 fragments. The biofilm was not present on the surface but in a layer slightly below it. The detection of biofilms was not directly related to the duration of the ulcer. It was not possible to establish a correlation between the size of the lesion and the presence of these microorganisms due to the small sample size.

CONCLUSIONS
Our findings indicate that detecting biofilm in venous ulcers is challenging, as it does not uniformly occur throughout the wound bed, can occur at different depths, and is often not present on the wound surface. There is a need to develop studies that can contribute to the detection of biofilm in clinical practice.
Number of interventional clinical trials registered per million population per country worldwide
Authors: Bjerg Jonas Leth , Nikolova Dimitrinka , Gluud Christian 
Published: November 2024

AbstractBackgroundHistorically, Sweden and Denmark have excelled in clinical trial publications per million population, but many trials have remained unpublished. Enforceable policies for trial registration before launch, made global and national clinical research assessments possible. The World Health Organisation (WHO) hosts the International Clinical Trials Registry Platform (ICTRP) for interventional clinical trials, with data from 1999.ObjectiveTo find out if the retrospective or prospective trial registration activities per million population per country during the 2009 to 2022 period have improved after establishing the number of interventional clinical trials registered per million population per country during the 1999 to 2022 period.MethodsWe used the WHO ICTRP to extract the numbers of registered interventional clinical trials. We entered data in Microsoft Excel to analyse two separate periods, 1999 to 2022 and 2009 to 2022. The second period aimed at filtering out the pickup of the registration requirements. To obtain the trial registration activity by country, we divided the number of interventional clinical trials registered by the country’s population in millions. Information on population numbers originated from the World Bank, the Central Intelligence Agency World Factbook, and The National Institute of Statistics and Economic Studies (of France) as of 2022. We collected data as of 03-01-2024.ResultsIn February 2023, there were 943.113 interventional clinical trials on the ICTRP. After excluding 32.309 trials with unknown country of origin, 910.804 trials from 229 countries and territories were analysed. For countries or territories with populations over 1 million, the top five in interventional clinical trial registrations per million during 1999-2022 were Denmark, Estonia, Belgium, The Netherlands, and Latvia. For 2009-2022, they were Denmark, Estonia, Belgium, The Netherlands, and New Zealand. The top five overall, irrespective of population, for both periods were Pitcairn, The Vatican, Tokelau, Niue, and Denmark.ConclusionsSince 1999, there has been worldwide growth in interventional trial registrations, especially among top-contributing countries. The global average stands at approximately 115 registered trials per million people from 1999 to 2022, highlighting the need for continued efforts to improve trial registration and production. Smaller Western countries lead in interventional clinical trials per million population.
Tiled PCR amplification-based Whole Genome Sequencing and Phylogenetic Classification Accelerate the Implementation of Respiratory Syncytial Virus Genomic surveillance in Canada as a Pilot Study
Authors: Gao Ruimin , Buchanan Cody , Dust Kerry , Van Caeseele Paul , Wong Henry , Sjaarda Calvin , Sheth Prameet M. , Jassem Agatha N. , Minion Jessica , Bastien Nathalie 
Published: November 2024

ABSTRACTWhole genome sequencing (WGS) has emerged as a powerful tool to facilitate the study of existing and emerging infectious diseases. WGS-based genomic surveillance provides information on the genetic diversity and tracks the evolution of important viral pathogens including Respiratory Syncytial Virus (RSV). Development and implementation of robust tiled multiplex PCR amplification-based WGS assays will facilitate high-throughput RSV surveillance initiatives. In this study, we developed multiplex PCR assays for targeted enrichment of viral genomes using PrimalScheme (http://primal.zibraproject.org) to amplify over 97% of the genome in the majority of contemporaneous specimens tested. A pilot dataset comprising 52 RSVA and 37 RSVB genomes derived from Canadian clinical specimens during the 2022-2023 respiratory virus season were used to perform phylogenetic analyses using both near complete genome and Glycoprotein (G) sequences. Overall, the RSV phylogenetic tree built with whole genomes showed identical lineage clusters as that compared to the G gene, but showed more confidence and discriminatory features within individual lineage. Moreover, availability of whole genomes enabled the identification of a broader range of mutations, for instance the identified S377N, K272M, S276N, S211N, S206I and S209Q in Canadian fusion proteins that could be potentially associated with effectiveness of vaccines or antiviral-based therapeutics. In conclusion, the tiled-PCR amplification assays described offer a more streamlined approach to facilitate high-throughput, high sensitivity of RSV WGS, which is capable of supporting enhanced genomic surveillance initiatives, as well as the more comprehensive genomic analyses required to inform public health strategies for the development and usage of vaccines and antiviral drugs.IMPORTANCEWe present assays to efficiently sequence genomes of the RSVA and RSVB. This enables researchers and public health agencies to acquire high-quality genomic data using rapid and cost-effective approaches. Genomic data based comparative analysis can be used to conduct surveillance and monitor circulating isolates for efficacy of vaccines and antiviral therapeutics.
Cumulative dose responses for adapting biological systems
Authors: Gupta Ankit , Sontag Eduardo D. 
Published: November 2024

AbstractThis paper introduces the notion of cumulative dose response (cDR). The cDR is the area under the plot of a response variable, an integral taken over a fixed time interval and seen as a function of an input parameter. This work was motivated by the accumulation of cytokines resulting from T cell stimulation, where a non-monotonic cDR has been observed experimentally. However, the notion is of general applicability. A surprising conclusion is that incoherent feedforward loops studied in the systems biology literature, though capable of non-monotonic dose responses, can be mathematically shown to always result in monotonic cDR.
Perfusion via chemicals removes the DNA content of rabbit hearts while keeping the collagen and glycosaminoglycan unaltered
Authors: Seitzhaparova Banu , Kadyr Sanazar , Timur Leya , Mirasbek Baisunkar , Zhakypbekova Aida , Lesbekov Timur , Erisken Cevat 
Published: November 2024

AbstractDespite new approaches in the treatment of cardiovascular disease (CVD) such as percutaneous coronary intervention, coronary artery bypass graft, and left ventricular assist devices, which cannot fully compensate for the effectiveness of the original heart, heart transplantation still remains as the most effective solution.A growing body of literature recognizes the importance of developing a whole heart constructed from living tissues to provide an alternative option for patients suffering from diseases of the cardiovascular system. A potential solution that shows a promise is to generate cell-free, i.e., decellularized, scaffolds using native heart tissue to be later cellularized and transplanted. This study reports the decellularization process and efficiency in an effort to create a whole heart scaffold. The hearts harvested from rabbits were perfused and the final bioartificial scaffolds were characterized for the efficiency of decellularization in terms of DNA content, collagen, and glycosaminoglycan. The compressive biomechanical properties of decellularized and native hearts were also determined and compared. Findings revealed that the DNA content of decellularized hearts was significantly reduced while keeping collagen and GAG content unchanged. Biomechanical properties of the hearth became inferior upon removal of the nuclear material. Decellularized hearts have significant importance in treating CVD as they serve as bioartificial hearts, providing a more clinically relevant model for potential human use.Future work will focus on the recellularization of the heart using induced pluripotent or embryonic stem cells to test its functionality.
Covalent inhibition of the SARS-CoV-2 NiRAN domain via an active-site cysteine
Authors: Hernandez Genaro , Osinski Adam , Majumdar Abir , Eitson Jennifer L. , Antczak Monika , Pawłowski Krzysztof , Niederstrasser Hanspeter , Servage Kelly A. , Posner Bruce , Schoggins John W. , Ready Joseph A. , Tagliabracci Vincent S. 
Published: November 2024

AbstractThe kinase-like NiRAN domain of nsp12 in SARS-CoV-2 catalyzes the formation of the 5’ RNA cap structure. This activity is required for viral replication, offering a new target for the development of antivirals. Here, we develop a high-throughput assay to screen for small molecule inhibitors targeting the SARS-CoV-2 NiRAN domain. We identified NCI-2, a compound with a reactive chloromethyl group that covalently binds to an active site cysteine (Cys53) in the NiRAN domain, inhibiting its activity. NCI-2 can enter cells, bind to, and inactivate ectopically expressed nsp12. A cryo-EM reconstruction of the SARS-CoV-2 replication-transcription complex (RTC) bound to NCI-2 offers a detailed structural blueprint for rational drug design. Although NCI-2 showed limited potency against SARS-CoV-2 replication in cells, our work lays the groundwork for developing more potent and selective inhibitors targeting the NiRAN domain. This approach presents a promising therapeutic strategy for effectively combating COVID-19 and potentially mitigating future coronavirus outbreaks.
Improved Deep Learning Prediction of TCR-HLA Associations
Authors: Li Fumin , Liu Si , Sun Wei 
Published: November 2024

AbstractUnderstanding the relationship between T cell receptors (TCRs) and human leukocyte antigens (HLAs) is essential for elucidating immune response specificity, uncovering mechanisms of autoimmunity, and advancing targeted immunotherapies. We have previously developed a deep learning method, DePTH (Deep Learning Prediction of TCR-HLA associations), to predict the association between a TCR and an HLA based on their amino acid sequences. In this work, we evaluated the performance of DePTH in two additional datasets, and investigated the influence of two potential confounding factors: TCR generation probability and the sequence length of CDR3 (Complementarity-Determining Region 3), which is a key region in the antigen-binding site of TCRs. Building on these insights, we combined training data from two datasets to train a new version of DePTH: DePTH 2.0.
Key Regulatory Elements of the TGFβ-LRRC15 Axis Predict Disease Progression and Immunotherapy Resistance Across Cancer Types
Authors: Storey Claire M. , Cheng Michael , Altai Mohamed , Park Julie E. , Tran Julie , Lueong Smiths S. , Thorek Daniel , Mao Liqun , Zedan Wahed , Yuen Constance , Ridley Alexander , Trajovic-Arsic Marija , Herrmann Ken , Subuhdi Sumit K. , Siddiqui Bilal A. , Lückerath Katharina , Siveke Jens , Damoiseaux Robert , Yang Xia , Ulmert David 
Published: November 2024

ABSTRACTTransforming growth factor-beta (TGFβ) has dual roles in cancer, initially suppressing tumors but later promoting metastasis and immune evasion. Efforts to inhibit TGFβ have been largely unsuccessful due to significant toxicity and indiscriminate immunosuppression. Leucine-rich repeat-containing protein 15 (LRRC15) is a TGFβ-regulated antigen expressed by mesenchymal-derived cancer cells and cancer-associated fibroblasts (CAFs). In preclinical studies, ablation of TGFβ-driven LRRC15+ CAFs increased tumor infiltration of CD8+ T cells. However, the underlying pathobiological mechanisms prompting TGFβ’s upregulation of LRRC15 expression are unclear. Using an integrated approach combining functional compound screening with single-cell RNA sequencing, we reveal key genomic features regulating TGFβ’s ability to increase LRRC15 expression on cancer cells. Construction of gene regulatory networks converged our analyses on four key genes—MMP2, SPARC, TGFβR2,andWNT5B—central to TGFβ-induced LRRC15 pathobiology. Validation of these genes in cell models and their use in predicting immunotherapy responses highlight their potential in refining immunotherapy strategies and personalizing co-treatment options.