bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brief Report: Differentiated Service Delivery Framework for People With Multidrug-Resistant Tuberculosis and HIV Coinfection
Authors: Reis Karl , Wolf Allison , Perumal Rubeshan , Seepamore Boitumelo , Guzman Kevin , Ross Jesse , Cheung Ying Kuen K. , Amico K. Rivet , Brust James C. M. , Padayatchi Nesri , Friedland Gerald , Naidoo Kogieleum , Daftary Amrita , Zelnick Jennifer , O'Donnell Max 
Published: February 2024

Introduction:
For people living with HIV/AIDS, care is commonly delivered through differentiated service delivery (DSD). Although people with multidrug-resistant tuberculosis (MDR-TB) and HIV/AIDS experience severe treatment-associated challenges, there is no DSD model to support their treatment. In this study, we defined patterns of medication adherence and characterized longitudinal barriers to inform development of an MDR-TB/HIV DSD framework.

Methods:
Adults with MDR-TB and HIV initiating bedaquiline (BDQ) and receiving antiretroviral therapy (ART) in KwaZulu-Natal, South Africa, were enrolled and followed through the end of MDR-TB treatment. Electronic dose monitoring devices measured BDQ and ART adherence. Longitudinal focus groups were conducted and transcripts analyzed thematically to describe discrete treatment stage-specific and cross-cutting treatment challenges.

Results:
Two hundred eighty-three participants were enrolled and followed through treatment completion (median 17.8 months [interquartile range 16.5–20.2]). Thirteen focus groups were conducted. Most participants (82.7%, 234/283) maintained high adherence (mean BDQ adherence 95.3%; mean ART adherence 85.5%), but an adherence-challenged subpopulation with <85% cumulative adherence (17.3%, 49/283) had significant declines in mean weekly BDQ adherence from 94.9% to 39.9% (P < 0.0001) and mean weekly ART adherence from 83.9% to 26.6% (P < 0.0001) over 6 months. Psychosocial, behavioral, and structural obstacles identified in qualitative data were associated with adherence deficits in discrete treatment stages and identified potential stage-specific interventions.

Conclusions:
A DSD framework for MDR-TB/HIV should intensify support for adherence-challenged subpopulations, provide multimodal support for adherence across the treatment course, and account for psychosocial, behavioral, and structural challenges linked to discrete treatment stages.
PRMT6-FOXO3A ATTENUATES APOPTOSIS BY UPREGULATING PARKIN EXPRESSION IN INTESTINAL ISCHEMIA-REPERFUSION INJURY
Authors: Wu Xinwan , Zhou Yu , Xu Hongjiao , Zhang Xinyi , Yao Liangfang , Li Jinbao , Li Xiang 
Published: February 2024

ABSTRACT
Intestinal ischemia-reperfusion injury (IIRI) is a serious disease with high morbidity and mortality. This study aims to investigate the potential regulatory mechanisms involving protein arginine methyltransferase 6 (PRMT6), Forkhead box O3a (FoxO3a), and Parkin in IIRI and elucidate their roles in mediating cell apoptosis. The IIRI animal model was established and confirmed using hematoxylin and eosin staining. Oxygen-glucose deprivation and reperfusion (OGD/R) cell model was established to mimic ischemic injury in vitro. Transient transfection was used to overexpress or knock down genes. Cell death or apoptosis was assessed by propidium iodide staining, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and flow cytometry. The expression of proteins was detected by western blot. The histopathology observed by hematoxylin and eosin staining suggested that the IIRI animal model was successfully established. Our findings revealed that IIRI resulted in increased Bax and decreased Bcl-2 levels. In vitro experiments showed that overexpression of Parkin decreased OGD/R injury and suppressed elevation of Bax/Bcl-2. PRMT6 regulated the methylation level of FoxO3a. Moreover, FoxO3a directly binds to Parkin, and FoxO3a overexpression reduced OGD/R-induced cell death and regulation of Parkin. Overexpression of PRMT6 can attenuate the downregulation of Parkin and elevation of Bax/Bcl-2 caused by OGD/R. Knockdown of PRMT6 promoted apoptosis in intestinal epithelial cells of OGD/R group, while PRMT6 overexpression exhibited the opposite effect. Notably, the levels of PRMT6, FoxO3a, and Parkin were decreased in IIRI mouse intestinal tissue. Knocking out PRMT6 causes a significant decrease in the lifespan of mice. Altogether, our results demonstrated that PRMT6 upregulated the expression of Parkin by regulating FoxO3a methylation level, attenuating the apoptosis induced by IIRI.
Recent Changes in the Management of High-Grade Blunt Pancreatic Injury in Children: A Nationwide Trend Analysis
Authors: Katsura Morihiro , Ikenoue Tatsuyoshi , Aoki Makoto , Kuriyama Akira , Takahashi Kyosuke , Schellenberg Morgan , Martin Matthew J , Inaba Kenji , Matsushima Kazuhide 
Published: February 2024

BACKGROUND:
The optimal management of pediatric patients with high-grade blunt pancreatic injury (BPI) involving the main pancreatic duct remains controversial. This study aimed to assess the nationwide trends in the management of pediatric high-grade BPI at pediatric (PTC), mixed (MTC), and adult trauma centers (ATC).

STUDY DESIGN:
This is a retrospective observational study of the National Trauma Data Bank. We included pediatric patients (age 16 years or less) sustaining high-grade BPI (Abbreviated Injury Scale 3 or more) from 2011 to 2021. Patients who did not undergo pancreatic operation were categorized into the nonoperative management (NOM) group. Trauma centers were defined as PTC (level I/II pediatric only), MTC (level I/II adult and pediatric), and ATC (level I/II adult only). Primary outcome was the proportion of patients undergoing NOM, and secondary outcomes included the use of ERCP and in-hospital mortality. A Cochran–Armitage test was used to analyze the trend.

RESULTS:
A total of 811 patients were analyzed. The median age was 9 years (interquartile range 6 to 13), 64% were male patients, and the median injury severity score was 17 (interquartile range 10 to 25). During the study period, there was a significant upward linear trend in the use of NOM and ERCP among the overall cohort (range 48% to 66%; ptrend = 0.033, range 6.1% to 19%; ptrend = 0.030, respectively). The significant upward trend for NOM was maintained in the subgroup of patients at PTC and MTC (ptrend = 0.037), whereas no significant trend was observed at ATC (ptrend = 0.61). There was no significant trend in in-hospital mortality (ptrend = 0.38).

CONCLUSIONS:
For the management of pediatric patients with high-grade BPI, this study found a significant trend toward increasing use of NOM and ERCP without mortality deterioration, especially at PTC and MTC.
Is SARS-CoV-2 elimination or mitigation best? Regional and disease characteristics determine the recommended strategy
Authors: Martignoni Maria M. , Arino Julien , Hurford Amy 
Published: February 2024

AbstractPublic health responses to the COVID-19 pandemic varied across the world. Some countries (e.g., mainland China, New Zealand, and Taiwan) implemented elimination strategies involving strict travel measures and periods of rigorous nonpharmaceutical interventions (NPIs) in the community, aiming to achieve periods with no disease spread; while others (e.g., many European countries and the United States of America) implemented mitigation strategies involving less strict NPIs for prolonged periods, aiming to limit community spread. Travel measures and community NPIs have high economic and social costs, and there is a need for guidelines that evaluate the appropriateness of an elimination or mitigation strategy in regional contexts. To guide decisions, we identify key criteria and provide indicators and visualizations to help answer each question. Considerations include determining whether disease elimination is: (1) necessary to ensure health care provision; (2) feasible from an epidemiological point of view; and (3) cost effective when considering, in particular, the economic costs of travel measures and treating infections. We discuss our recommendations by considering the regional and economic variability of Canadian provinces and territories, and the epidemiological characteristics of different SARS-CoV-2 variants. While elimination may be a preferable strategy for regions with limited health care capacity, low travel volumes, and few port of entries, mitigation may be more feasible in large urban areas with dense infrastructure, strong economies, and with high connectivity to other regions.
GenerRNA: A generative pre-trained language model forde novoRNA design
Authors: Zhao Yichong , Oono Kenta , Takizawa Hiroki , Kotera Masaaki 
Published: February 2024

AbstractThe design of RNA plays a crucial role in developing RNA vaccines, nucleic acid therapeutics, and innovative biotechnological tools. Nevertheless, existing techniques lack versatility across various tasks and frequently suffer from a deficiency of automated generation. Inspired by the remarkable success of Large Language Models (LLMs) in the realm of protein and molecule design, we present GenerRNA, the first large-scale pre-trained model for RNA generation, aiming to further automate RNA design. Our approach eliminates the need for secondary structure or other prior knowledge and is capable ofde novogeneration of RNA with stable secondary structures while ensuring its distinctiveness from existing sequences. This widens our exploration of RNA space, thereby enriching our understanding of RNA structures and functions. Moreover, GenerRNA is fine-tunable on smaller, more specialized datasets for particular subtasks. This flexibility and versatility enables the generation of RNAs with desired specific functionalities or properties. Upon fine-tuning GenerRNA, we successfully generated novel RNA sequences exhibiting high affinity for target proteins. GenerRNA is freely available at the following repository:https://github.com/pfnet-research/GenerRNA
Don’t Leave the Past Behind: How Larval Experience Shapes Pupal Antipredator Response inAedes aegypti
Authors: Rawat Kanika , Bhambore Akshaye Anand , Isvaran Kavita 
Published: February 2024

AbstractAnimals use predation encounters or risk experiences to influence their future antipredator responses. Such carryover effects of predation can benefit them by enhancing their antipredator behaviour and thereby decreasing their risk of mortality through predation. Despite these fitness benefits, behavioural carryovers of predation past may not be a common phenomenon in complex life cycles. Complex life cycles pose a unique evolutionary and physiological challenge to behavioural carryovers since every life stage is distinct in morphology, physiology, and function. Each life stage of a complex life cycle is expected to evolve its independent response based on the real-time threat level and manage the trade-offs accordingly. Along with the evolutionary challenge, physiological barriers can hamper behavioural carryovers, especially in holometabolous insects, where we observe extensive tissue remodelling and developmental compartmentalisation. We investigated behavioural carryover in the holometabolous mosquito model system,Aedes aegypti. We asked whether predation risk during a life stage carries over to the subsequent stage, influencing its behaviour, or if the next life stage responds according to its threat environment.Aedes aegyptihas four major stages– egg, larva, pupa, and adult. We examined the effect of predation-risk experience across larval and pupal stages. Larval and pupal stages differ in morphology, physiology and function. They share the same habitat and, therefore, similar threats. We manipulated the threat of predation experienced by larvae and investigated its influence on pupal behaviour. We found behavioural carryover in the pupal stage for the first time and discovered exciting interactions between past experiences and the current threat environment. Our study underscores the crucial role of predation pressure in shaping the evolution of complex life cycles, emphasising the significance of early experiences with predators in influencing behavioural traits across distinct life stages.
A Novel, Open-Source Virtual Reality Platform for Dendritic Spine Analysis
Authors: Reimer Marike L , Kauer Sierra D , Benson Curtis A , King Jared F , Patwa Siraj , Feng Sarah , Estacion Maile A , Bangalore Lakshmi , Waxman Stephen G , Tan Andrew M 
Published: February 2024

SummaryNeuroanatomy is fundamental to understanding the nervous system, particularly dendritic spines, which are vital for synaptic transmission and change in response to injury or disease. Advancements in imaging have allowed for detailed 3D visualization of these structures. However, existing tools for analyzing dendritic spine morphology are limited. To address this, we developed an open-source, virtual reality (VR) Structural Analysis Software Ecosystem (coined “VR-SASE”) that offers a powerful, intuitive approach for analyzing dendritic spines. Our validation process confirmed the method’s superior accuracy, outperforming recognized gold standard neural reconstruction techniques. Importantly, the VR-SASE workflow automatically calculates key morphological metrics such as dendritic spine length, volume, and surface area, and reliably replicates established datasets from published dendritic spine studies. By integrating the Neurodata Without Borders (NWB) data standard and DataJoint, VR-SASE also aligns with FAIR principles--guidelines aimed at improving the findability, accessibility, interoperability, and reusability of digital assets--enhancing data usability and longevity in neuroscience research.MotivationTechnological limitations of available image-analysis tools for analyzing 3D fine-structure hinders effective research and is often costly. An accessible and efficient solution is crucial to overcome these research challenges. We addressed this by integrating the NWB data standard and DataJoint technology into an open-source, virtual reality workflow, enhancing dendritic spine analysis.
Genome-wide diversity in lowland and highland maize landraces from southern South America: population genetics insights to assist conservation
Authors: Dominguez Pia Guadalupe , Gutierrez Angela Veronica , Fass Monica Irina , Filippi Carla Valeria , Vera Pablo , Puebla Andrea , Defacio Raquel Alicia , Paniego Norma Beatriz , Lia Veronica Viviana 
Published: February 2024

AbstractMaize (Zea maysssp.mays L.) landraces are traditional American crops with high genetic variability that conform a source of original alleles for conventional maize breeding. Northern Argentina, one the southernmost regions of traditional maize cultivation in the Americas, harbours around 57 races traditionally grown in two regions with contrasting environmental conditions, namely the Andean mountains in the Northwest and the tropical grasslands and Atlantic Forest in the Northeast. These races encounter diverse threats to their genetic diversity and persistence in their regions of origin, with climate change standing out as one of the major challenges. In this work, we use genome-wide SNPs derived from ddRADseq to study the genetic diversity of individuals representing the five groups previously described for this area. This allowed us to distinguish two clearly differentiated gene pools, the Highland Northwestern maize (HNWA) and the Floury Northeastern maize (FNEA). Subsequently, we employed Essential Biodiversity Variables at the genetic level, as proposed by the Group on Earth Observations Biodiversity Observation Network (GEO BON), to evaluate the conservation status of these two groups. This assessment encompassed genetic diversity (Pi), inbreeding coefficient (F), and effective population size (Ne). FNEA showed low Ne values and high F values, while HNWA showed low Ne values and low Pi values, indicating that further genetic erosion is imminent for these landraces. Outlier detection methods allowed identification of putative adaptive genomic regions, consistent with previously reported flowering-time loci and chromosomal regions displaying introgression from the teosinteZea maysssp.mexicana. Finally, species distribution models were obtained for two future climate scenarios, showing a notable reduction in the potential planting area of HNWA and a shift in the cultivation areas of FNEA. Taken together, these results suggest that maize landraces from Northern Argentina may not be able to cope with climate change. Therefore, active conservation policies are advisable.
PKSmart: An Open-Source Computational Model to Predictin vivoPharmacokinetics of Small Molecules
Authors: Seal Srijit , Trapotsi Maria-Anna , Subramanian Vigneshwari , Spjuth Ola , Greene Nigel , Bender Andreas 
Published: February 2024

ABSTRACTDrug exposure is a key contributor to the safety and efficacy of drugs. It can be defined using human pharmacokinetics (PK) parameters that affect the blood concentration profile of a drug, such as steady-state volume of distribution (VDss), total body clearance (CL), half-life (t½), fraction unbound in plasma (fu) and mean residence time (MRT). In this work, we used molecular structural fingerprints, physicochemical properties, and predicted animal PK data as features to model the human PK parameters VDss, CL, t½, fu and MRT for 1,283 unique compounds. First, we predicted animal PK parameters [VDss, CL, fu] for rats, dogs, and monkeys for 372 unique compounds using molecular structural fingerprints and physicochemical properties. Second, we used Morgan fingerprints, Mordred descriptors and predicted animal PK parameters in a hyperparameter-optimised Random Forest algorithm to predict human PK parameters. When validated using repeated nested cross-validation, human VDss was best predicted with an R2of 0.55 and a Geometric Mean Fold Error (GMFE) of 2.09; CL with accuracies of R2=0.31 and GMFE=2.43, fu with R2=0.61 and GMFE=2.81, MRT with R2=0.28 and GMFE=2.49, and t½ with R2=0.31 and GMFE=2.46 for models combining Morgan fingerprints, Mordred descriptors and predicted animal PK parameters. We evaluated models with an external test set comprising 315 compounds for VDss (R2=0.33 and GMFE=2.58) and CL (R2=0.45 and GMFE=1.98). We compared our models with proprietary pharmacokinetic (PK) models from AstraZeneca and found that model predictions were similar with Pearson correlations ranging from 0.77-0.78 for human PK parameters of VDss and fu and 0.46-0.71 for animal (dog and rat) PK parameters of VDss, CL and fu. To the best of our knowledge, this is the first work that publicly releases PK models on par with industry-standard models. Early assessment and integration of predicted PK properties are crucial, such as in DMTA cycles, which is possible with models in this study based on the input of only chemical structures. We developed a webhosted application PKSmart (https://broad.io/PKSmart) which users can access using a web browser with all code also downloadable for local use.Abstract FigureFigure:For TOC Only
Automated pupillometry to detect residual consciousness in acute brain injury
Authors: Othman Marwan H. , Olsen Markus Harboe , Tanderup Hansen Karen Irgens , Amir Moshgan , Jensen Helene Ravnholt , Nyholm Benjamin , Møller Kirsten , Kjærgaard Jesper , Kondziella Daniel 
Published: February 2024

AbstractBackgroundIdentifying residual consciousness in patients with disorders of consciousness (DoC) in the intensive care unit (ICU) is crucial for treatment decisions, but sensitive low-cost bedside markers are missing. We investigated whether automated pupillometry combined with passive and active cognitive paradigms can identify residual consciousness in ICU patients with traumatic or non-traumatic DoC.MethodsIn a prospective observational cohort study, clinically low- or unresponsive ICU patients with traumatic and non-traumatic DoC were enrolled from neurological and non-neurological ICUs at a tertiary referral center (Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark). Age- and sex-matched healthy volunteers served as controls. Participants with eye disorders were excluded. Patients were categorized into those without (coma or unresponsive wakefulness syndrome, ≤UWS) or with (minimally conscious state or better, ≥MCS) clinical signs of residual consciousness. Using automated pupillometry, we recorded pupillary dilation as a response to passive (visual and auditory stimuli) and active (mental arithmetic) cognitive paradigms, with success criteria depending on the specific task (e.g., ≥3 of 5 pupillary dilations on 5 consecutive mental arithmetic tasks).ResultsWe obtained 699 pupillometry recordings at 178 time points from 91 brain-injured ICU patients (mean age 60±13.8 years; 31% women; 49.5% non-traumatic brain injuries). Recordings were also obtained from 26 matched controls (59±14.8 years, 38% women). Passive paradigms yielded limited distinctions between patient groups and controls. However, active paradigms involving mental arithmetic enabled discrimination between different states of consciousness. With mental arithmetic of moderate complexity, ≥3 pupillary dilations were seen in 50.0% ≥MCS patients and 17.8% ≤UWS patients (OR 4.56; 95% CI 2.09-10.10,p<0.001). In comparison, 76.9% healthy controls responded with ≥3 pupillary dilations (p=0.028). Results remained consistent across sensitivity analyses using different thresholds for success. Spearman’s Rank analysis underscored the robust association between pupillary dilations during mental arithmetic and consciousness levels (rho=1,p=0.017). Notably, one behaviorally unresponsive patient demonstrated persistent command-following behavior two weeks before overt signs of awareness, suggesting a state of prolonged CMD.ConclusionsAutomated pupillometry combined with mental arithmetic can identify cognitive efforts, and hence residual consciousness, in ICU patients with acute DoC.
Brain Age Analysis and Dementia Classification using Convolutional Neural Networks trained on Diffusion MRI: Tests in Indian and North American Cohorts
Authors: Chattopadhyay Tamoghna , Joshy Neha Ann , Ozarkar Saket S. , Buwa Ketaki , Feng Yixue , Laltoo Emily , Thomopoulos Sophia I. , Villalon Julio E. , Joshi Himanshu , Venkatasubramanian Ganesan , John John P. , Thompson Paul M. 
Published: February 2024

AbstractDeep learning models based on convolutional neural networks (CNNs) have been used to classify Alzheimer’s disease or infer dementia severity from T1-weighted brain MRI scans. Here, we examine the value of adding diffusion-weighted MRI (dMRI) as an input to these models. Much research in this area focuses on specific datasets such as the Alzheimer’s Disease Neuroimaging Initiative (ADNI), which assesses people of North American, largely European ancestry, so we examine how models trained on ADNI, generalize to a new population dataset from India (the NIMHANS cohort). We first benchmark our models by predicting “brain age” - the task of predicting a person’s chronological age from their MRI scan and proceed to AD classification. We also evaluate the benefit of using a 3D CycleGAN approach to harmonize the imaging datasets before training the CNN models. Our experiments show that classification performance improves after harmonization in most cases, as well as better performance for dMRI as input.