bluuebunny/crossref_metadata_2025_split huggingface dataset:
End-user feedback of rapid diagnostics in rural Kenya
Authors: Beard Jeffrey W. , Pariser Daphne N. , Monticelli Stephanie , Miller Benjamin L. 
Published: February 2024

AbstractUnderserved communities in low-resource countries are disproportionately impacted by communicable diseases when compared to those in developed countries. These communities have limited access to life saving diagnostic laboratory tests making it difficult to treat communicable diseases like SARS-CoV-2 and Human Immunodeficiency Virus (HIV). Rapid diagnostic tests, like the COVID-19 antigen (Ag) test, play a crucial role in underserved communities by enabling fast and inexpensive diagnosis in low-resource settings. Unfortunately, these rapid test platforms often lack the accuracy and precision of their laboratory-based analogs, resulting in a need for improved rapid diagnostics. The World Health Organization’s (WHO) ASSURED (Affordable, Sensitive, Specific, User-friendly, Rapid and robust, Equipment-free, and Deliverable to end-users) criteria are often referenced in the development of diagnostic tests. In this work, we aim to provide guidance to the “user-friendly” component of ASSURED through end-user surveys taken in rural Kenya. In these surveys, we examine the user-friendliness of two of the most commonly used rapid diagnostic tests, the COVID-19 Ag test and pregnancy test, by assessing participants’ familiarity with the tests, their opinion of test appearance, and the perceived complexity of the operator’s workflow. We also examine community acceptance and desire for a self-test for the highly stigmatized HIV. We intend these results to help guide developers of future rapid diagnostic tests intended for low-resource communities.
Demonstrating the Beneficial Effect of Low Protein Diet in Primary Sclerosing Cholangitis through a Randomized Clinical Trial and Multi-omics Data Analysis
Authors: Yin Xiaole , Sasson Gila , Sun Zheng , Ke Shanlin , Babazadeh Demsina , Mahmood Shaikh Danish , Andrews Macie , Hurwitz Shelley , Chikowore Tinashe , Paul Maia , Javier Nadine , Dave Malav , Austin Alexandra , Gray Linda , Steinberg Francene , Souza Elaine , Bowlus Christopher , Liu Yang-Yu , Korzenik Joshua 
Published: February 2024

ABSTRACTPrimary sclerosing cholangitis (PSC), a progressive cholestatic hepatobiliary disease characterized by inflammation and fibrosis of the bile ducts, has a pathophysiology that is not understood. No effective therapies exist. The only treatment option for PSC is liver transplant. We undertook a pilot randomized trial of diet to investigate the pathophysiology of the disease, the role of diet and to advance potential therapy. We enrolled 20 patients with PSC and randomly assigned them to a Low Protein/low sulfur Diet (LPD, n=10) or the Specific Carbohydrate Diet (SCD, n=10) for 8 weeks. Results showed that low protein intake benefits PSC patients, whereas higher protein levels exacerbate the condition. We further identified gut bacterial markers useful for distinguishing LPD responders (mostly PSC with concomitant ulcerative colitis) from non-responders. Additionally, by integrating multi-omics data, we propose that this diet modifies the intestinal sulfur cycle reducing hydrogen sulfide (H2S) production. Our findings provide an understanding of the beneficial effect of LPD as well as insights into a possible key driver of inflammation in PSC.
Call Me Dr. Ishmael: Trends in Electronic Health Record Notes Available at ED Visits and Admissions
Authors: Patterson Brian W. , Hekman Daniel J , Liao Frank , Hamedani Azita , Shah Manish N. , Afshar Majid 
Published: February 2024

AbstractObjectiveNumerous studies have identified information overload as a key issue for electronic health records (EHRs). This study describes the amount of text data across all notes available to emergency physicians in the EHR, trended over the time since EHR establishment.Materials and MethodsWe conducted a retrospective analysis of EHR data from a large healthcare system, examining the number of notes and corresponding number of total words and total tokens across all notes available to physicians during patient encounters in the emergency department (ED). We assessed the change in these metrics over a 17-year period between 2006 and 2023.ResultsThe study cohort included 730,968 ED visits made by 293,559 unique patients and a total note count of 132,574,964. The median note count for all encounters in 2006 was 7 (IQR: 3 - 18), accounting for 1,894 words (IQR: 538 - 5,864). By the last full year of the study period in 2022, the median number of notes had grown to 380 (IQR: 93 - 1,008), representing 61,591 words (IQR: 13,621 - 174,152). Note and word counts were higher for admitted patients.ConclusionThe volume of notes available for review by providers has increased by over 30-fold in the 17 years since the implementation of the EHR at a large health system. The task of reviewing these notes has become correspondingly more difficult. These data point to the critical need for new strategies and tools for filtering, synthesizing, and summarizing information to achieve the promise of the medical record.
A Cost-effectiveness analysis of Nivolumab plus chemotherapy for the first-line treatment of locally advanced or metastatic gastric/GEJ/oesophageal adenocarcinoma in the United States of America
Authors: Zhou Jin , Tang Yukai , Li Geli 
Published: February 2024

AbstractBackgroundNivolumab in combination with chemotherapy significantly improves survival in patients with gastric/gastroesophageal junction (G/GEJ)/esophageal adenocarcinoma.The purpose of this study was to evaluate the cost-effectiveness of Nivolumab plus chemotherapy for G/GEJ/esophageal adenocarcinoma.MethodsA Markov model was developed on the basis of the US healthcare payers’ perspectives. We estimated the costs and summarised their effectiveness as quality-adjusted life-years (QALYs). One-way and probabilistic sensitivity analyses were conducted to explore the impact of uncertainties on the cost-effectiveness’s results.ResultsThe incremental cost-effectiveness ratios (ICER) for Nivolumab plus chemotherapy($149636.97,1.24QALYs) verus chemotherapy($13941.06,0.75QALYs) is $135695.91 and the QALYs is 0.49.ConclusionsEvidence suggests that Nivolumab plus chemotherapy a for the first-line treatment of locally advanced or metastatic gastric/GEJ/oesophageal adenocarcinoma may be not a cost-effective choice.
“If I am free from diabetes, that itself will be the happiest thing”: A convergent mixed methods study of the lived experiences of young adults with type 2 diabetes in Mysore district, India
Authors: Gopisetty Nikhita R. , Muralidhar Kiranmayee , Ningaiah Nagalambika , Chinnappa Rani , Buono Mia , Jaykrishna Poornima , Madhivanan Purnima , Ariely Sumedha G. , Puffer Eve S. 
Published: February 2024

AbstractType 2 diabetes (T2D) has been occurring at younger ages of onset around the world. India’s population accounts for nearly 20% of the global disease burden. This study investigated the occurrence of depressive symptoms and qualitatively explored the lived experiences of 20 young adults living with T2D under the age of 35. We conducted a convergent mixed-methods study with the Patient Health Questionnaire (PHQ-9) and semi-structured interviews from June 2022 to July 2022 in Mysore district, India. Guided by the World Health Organization’s Commission on Social Determinants of Health conceptual framework and biopsychosocial frameworks, areas of inquiry included knowledge and perception about T2D, accessibility of healthcare resources, T2D-related self-care activities, and the impact of the condition on their daily life. Interviews were debriefed by the research team and analyzed thematically using NVivo 12. Participants were aged between 21 and 35 (mean: 30.8, SD: 4.2) and the majority were female (75%). Overall, 55% reported mild depression symptoms, 15% reported moderate to moderately severe depression symptoms; 5 participants (25%) reported suicidality. Sex, living in rural Mysore district, socioeconomic status, T2D duration, family history of T2D, T2D-induced complications, and T2D-related self-care behaviors were associated with depressive symptoms. Thematic analysis revealed 1) low knowledge about T2D, 2) substantial interpersonal and internalized stigma for having T2D at a young age, 3) financial and time constraints to seek and receive care, 4) self-perception as burdens to family members due to the cost and stress of living with T2D, 5) competing priorities with work and family, and 6) the power of social support in managing T2D. These themes were consistent across the sample, regardless of severity of depressive symptoms. Awareness campaigns and peer support programs may help reduce depressive symptoms and increase self-efficacy in this population.
Quantitative Characterization of Retinal Features in Translated OCTA
Authors: Badhon Rashadul Hasan , Thompson Atalie Carina , Lim Jennifer I. , Leng Theodore , Alam Minhaj Nur 
Published: February 2024

AbstractPurposeThis study explores the feasibility of using generative machine learning (ML) to translate Optical Coherence Tomography (OCT) images into Optical Coherence Tomography Angiography (OCTA) images, potentially bypassing the need for specialized OCTA hardware.MethodsThe method involved implementing a generative adversarial network framework that includes a 2D vascular segmentation model and a 2D OCTA image translation model. The study utilizes a public dataset of 500 patients, divided into subsets based on resolution and disease status, to validate the quality of TR-OCTA images. The validation employs several quality and quantitative metrics to compare the translated images with ground truth OCTAs (GT-OCTA). We then quantitatively characterize vascular features generated in TR-OCTAs with GT-OCTAs to assess the feasibility of using TR-OCTA for objective disease diagnosis.ResultTR-OCTAs showed high image quality in both 3 and 6 mm datasets (high-resolution, moderate structural similarity and contrast quality compared to GT-OCTAs). There were slight discrepancies in vascular metrics, especially in diseased patients. Blood vessel features like tortuosity and vessel perimeter index showed a better trend compared to density features which are affected by local vascular distortions.ConclusionThis study presents a promising solution to the limitations of OCTA adoption in clinical practice by using vascular features from TR-OCTA for disease detection.Translation relevanceThis study has the potential to significantly enhance the diagnostic process for retinal diseases by making detailed vascular imaging more widely available and reducing dependency on costly OCTA equipment.
Physiological effects of dual target DBS in an individual with Parkinson’s Disease and a sensing-enabled pulse generator
Authors: Cummins Daniel D. , Sandoval-Pistorius Stephanie S. , Cernera Stephanie , Fernandez-Gajardo Rodrigo , Hammer Lauren , Starr Philip A. 
Published: February 2024

AbstractIntroductionDeep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus (GP) is an established therapy for Parkinson’s disease (PD). Novel DBS devices can record local field potential (LFP) physiomarkers from the STN or GP. While beta (13-30 Hz) and gamma (40-90 Hz) STN and GP LFP oscillations correlate with PD motor severity and with therapeutic effects of treatments, STN-GP interactions in electrophysiology in patients with PD are not well characterized.MethodsSimultaneous bilateral STN and GP LFPs were recorded in a patient with PD who received bilateral STN-DBS and GP-DBS. Power spectra in each target and STN-GP coherence were assessed in various ON- and OFF-levodopa and DBS states, both at rest and with voluntary movement.ResultsOFF-levodopa and OFF-DBS, beta peaks were present at bilateral STN and GP, coincident with prominent STN-GP beta coherence. Levodopa and dual-target-DBS (simultaneous STN-DBS and GP-DBS) completely suppressed STN-GP coherence. Finely-tuned gamma (FTG) activity at half the stimulation frequency (62.5Hz) was seen in the STN during GP-DBS at rest. To assess the effects of movement on FTG activity, we recorded LFPs during instructed movement. We observed FTG activity in bilateral GP and bilateral STN during contralateral body movements while on GP-DBS and ON-levodopa. No FTG was seen with STN-DBS or dual-target-DBS.ConclusionDual-target-DBS and levodopa suppressed STN-GP coherence. FTG throughout the basal ganglia was induced by GP-DBS in the presence of levodopa and movement. This bilateral STN-FTG and GP-FTG corresponded with the least severe bradykinesia state, suggesting a pro-kinetic role for FTG.
Enhancing Mental Health Condition Detection on Social Media through Multi-Task Learning
Authors: Liu Jiawen , Su Menglu 
Published: February 2024

ABSTRACTObjectiveMental health conditions are traditionally modeled individually, which ignores the complex, interconnected nature of mental health disorders, which often share overlapping symptoms. This study aims to develop an integrated multi-task learning framework to enhance the detection of mental health conditions.MethodUtilizing datasets from Reddit’s SuicideWatch and Mental Health Collection (SWMH) and Psychiatric-disorder Symptoms (PsySym), the study develops a BERT-based multi-task learning framework. This framework leverages pre-trained embedding layers of BERT variants to capture linguistic nuances relevant to various mental health conditions from social media narratives. The approach is tested against the two datasets, comparing multitask modeling with a wide array of single-task baselines and large language models (LLM).ResultsThe multi-task learning framework demonstrated higher performance in efficiently predicting mental health conditions together compared to single-task models and general-purpose LLMs. Specifically, the framework achieved higher F1 scores across multiple conditions, with notable improvements in recall and precision metrics. This indicates more accurate modeling of mental health disorders when considered together, rather than in isolation.ConclusionThe study confirms the effectiveness of a multi-task learning approach in enhancing the detection of mental health conditions from social media data. It sets a new precedent in computational psychiatry and suggests future explorations into multi-task frameworks for deeper insights into mental health disorders.
Food Fermentation in Space Is Possible, Distinctive, and Beneficial
Authors: Coblentz Maggie , Evans Joshua D. , Kothe Caroline Isabel , Mak Tiffany , Valeron Nabila Rodriguez , Chwalek Patrick , Wejendorp Kim , Garg Shilpa , Pless Louisa , Mak Sarah , Sörensen Pia M. , Jahn Leonie Johanna , Ekblaw Ariel 
Published: February 2024

AbstractSpace exploration is expanding, which demands new technologies and enables new scientific questions. Food, as a bridge between disciplines, can bring these fundamental and applied goals together. Here we investigate whether food fermentation in space is possible, and if so, how it compares with fermentation on Earth. We fermented a miso, a traditional Japanese condiment, on the International Space Station over 30 days, and compared it with two earthbound controls. Using a specially-built environmental sensing box, we gathered metadata for temperature, relative humidity, pressure, and radiation. We analyzed the three misos with shotgun metagenomics to investigate the microbial communities’ composition and safety; whole genome sequencing to investigate the mutation rate ofAspergillus oryzae; untargeted metabolomics to quantify aromatic compounds, amino acids and organic acids; colorimetry to quantify color; and sensory analysis to describe the misos’ flavours and quantify liking and sensory difference. Across these datasets, we found that overall, the space miso is recognizable as a miso, suggesting fermentation in space is possible. We also found certain differences in the space miso: specifically the presence ofBacillus velezensis, a higher mutation rate ofA. oryzae, higher attributions of ‘roasted’ and ‘nutty’ flavours, and the most different sensory impression. Taken together, these observations suggest unique features of the space environment—what we might call ‘space terroir’—which could be harnessed to create more flavorful, nourishing foods for long-term space missions and to address fundamental questions about the biology of novel environments.Significance StatementOur study presents, to our knowledge, the first time a food product has been fermented in space. We demonstrate that fermentation in space is possible with safe and successful results, a proof of concept that offers fermentation as a new tool for space research and future long-term space exploration missions. We also document how the space environment shapes the fermentation process in unique ways, suggesting a ‘space terroir’. These findings on the feasibility and novelty of fermentation in space open up directions for further multidisciplinary research across science, health, systems design, and society and culture.
p24-Tango1 interactions ensure ER-Golgi interface stability and efficient transport
Authors: Yang Ke , Feng Zhi , Pastor-Pareja José C. 
Published: February 2024

ABSTRACTThe eukaryotic p24 family, consisting of α-, β-, γ- and δ-p24 subfamilies, has long been known to be involved in regulating secretion. Despite increasing interest in these proteins, fundamental questions remain about their role. Here, we systematically investigatedDrosophilap24 proteins. We discovered that members of all four p24 subfamilies are required for general secretion, and that their localizations between ER exit site (ERES) and Golgi are interdependent in an α→βδ→γ sequence. We also found that localization of p24 proteins and ERES determinant Tango1 requires interaction through their respective GOLD and SH3 lumenal domains, with Tango1 loss sending p24 proteins to the plasma membrane and vice versa. Finally, we show that p24 loss expands the COPII zone at ERES and increases the number of ER-Golgi vesicles, supporting a restrictive role of p24 proteins on vesicle budding for efficient transport. Our results reveal Tango1-p24 interplay as central to the generation of a stable ER-Golgi interface.SummaryYang et al. systematically analyze inDrosophilathe function of the four p24 protein subfamilies and discover that interaction with Tango1 is essential for their concentration between ER and Golgi and for efficiency of COPII-mediated general secretory transport.
Knockout of AMPA receptor binding protein Neuron-Specific Gene 2 (NSG2) enhances associative learning and cognitive flexibility
Authors: Zimmerman Amber J. , Serrano-Rodriguez Antonio , Wilson Sandy J. , Linsenbardt David N. , Brigman Jonathan L. , Weick Jason P. 
Published: February 2024

ABSTRACTThe vast majority of gene mutations and/or gene knockouts result in either no observable changes, or significant deficits in molecular, cellular, or organismal function. However, in a small number of cases, mutant animal models display enhancements in specific behaviors such as learning and memory. To date, most gene deletions shown to enhance cognitive ability generally affect a limited number of pathways such as NMDA receptor- and translation-dependent plasticity, or GABA receptor- and potassium channel-mediated inhibition. While endolysosomal trafficking of AMPA receptors is a critical mediator of synaptic plasticity, mutations in genes that affect AMPAR trafficking either have no effect or are deleterious for synaptic plasticity, learning and memory. NSG2 is one of the three-member family of Neuron-specific genes (NSG1-3), which have been shown to regulate endolysosomal trafficking of a number of proteins critical for neuronal function, including AMPAR subunits (GluA1-2). Based on these findings and the largely universal expression throughout mammalian brain, we predicted that genetic knockout of NSG2 would result in significant impairments across multiple behavioral modalities including motor, affective, and learning/memory paradigms. However, in the current study we show that loss of NSG2 had highly selective effects on associative learning and memory, leaving motor and affective behaviors intact. For instance, NSG2 KO animals performed equivalent to wild-type C57Bl/6n mice on rotarod and Catwalk motor tasks, and did not display alterations in anxiety-like behavior on open field and elevated zero maze tasks. However, NSG2 KO animals demonstrated enhanced recall in the Morris water maze, accelerated reversal learning in a touch-screen task, and accelerated acquisition and recall on a Trace Fear Conditioning task. Together, these data point to a specific involvement of NSG2 on multiple types of associative learning, and expand the repertoire of pathways that can be targeted for cognitive enhancement.
The importance of stereochemistry in the disorder-order continuum of protein-protein interactions
Authors: Newcombe Estella A. , Due Amanda D. , Sottini Andrea , Fernandes Catarina B. , Staby Lasse , Delaforge Elise , Bartling Christian R. O. , Brakti Inna , Bugge Katrine , Schuler Benjamin , Skriver Karen , Olsen Johan G. , Kragelund Birthe B. 
Published: February 2024

ABSTRACTIntrinsically disordered proteins can bindviathe formation of highly disordered protein complexes without the formation of 3D-structure. Most naturally occurring proteins are “left-handed” or levorotatory (L), made up only of L-amino acids, imprinting molecular structure and communication with stereochemistry. In contrast, their mirror image “right-handed” or dextrorotatory (D) amino acids are rare in Nature. Whether disordered protein complexes are truly independent of 3D-topology and thus of chiral constraints is not clear. To test the chiral constraints of disordered protein-protein interactions, a set of interacting protein pairs covering the disorder-order continuum was chosen as representative examples. By observing both the natural ligands and their stereochemical mirror images in free and bound states, we discovered that chirality was inconsequential in a fully disordered complex. However, if the interaction relied on the ligand undergoing coupled folding and binding, correct stereochemistry was essential. Between these extremes, binding could be observed for the D-ligand with a strength that correlated with the amount of disorder in the final complex. These findings have important implications for our understanding of protein-protein interactions, the molecular processes leading to complex formation, the use of D-peptides in drug discovery, and the chemistry of protein evolution of the first living entities on Earth.