bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using Simulation-Based Experiential Learning to Increase Students’ Ability to Analyze Increasingly Complex Global Health Challenges: A Mixed Methods Study
Authors: Khalid Ahmad Firas , George Megan A. , Eggen Clarissa , Sritharan Aaranee , Wali Faiza , Viens A. M. 
Published: December 2023

AbstractTraditional didactic teaching approaches fall short of adequately supporting diverse student learning styles. Complementing didactic teaching approaches with simulation-based experiential learning has shown promise in bridging the gap between theoretical knowledge and practical application. However, few studies have rigorously examined the outcomes of this approach in global health education and training. This study aims to evaluate the impact of the World Health Organization World Health Assembly Simulation (WHA Sim), a simulation-based experiential learning platform designed to enhance the application of students’ knowledge and skills in practical settings relating to global health governance.We employed a sequential mixed-method study between September 2022 and July 2023, starting with an anonymous survey among undergraduate students in the Faculty of Health at York University, in order to evaluate self-reported quantitative metrics related to students’ understanding of simulation-based learning prior to the WHA Sim. We also conducted qualitative interviews among participants of the WHA Sim from diverse health disciplines, aiming to capture multi-disciplinary perspectives. Data was analyzed using simple descriptive statistics for the quantitative data and a framework analysis for qualitative data.Among 39 survey respondents, 18 were interviewed. The WHA Sim bolstered a wide array of skills, including research capabilities, critical analysis, time management, and organizational effectiveness. Participants also reported improvements in effective interpersonal communication, public speaking, networking, and solution-driven dialogues. Interpersonal skills like collaboration and leadership were notably improved. Moreover, the simulation provided an enhanced understanding of complex issues and offered a fertile ground for career preparation, filling existing knowledge gaps more effectively than traditional learning environments.Findings demonstrate the value of simulation-based experiential learning among undergraduate students, which illustrates how the WHA Sim can serve as an effective learning tool within global health education and training.
Diabetes related emergency department visits among adults during the COVID-19 pandemic – an analysis of data from the New York City syndromic surveillance system
Authors: Zhilkova Anna , Lall Ramona , Mathes Robert , Chamany Shadi , Olson Donald 
Published: December 2023

AbstractObjectiveNew York City was an early epicenter of the COVID-19 pandemic. We aim to describe population level epidemiological trends in diabetes related emergency department (ED) visits among adults in New York City, for the period prior to and encompassing the first four waves of the pandemic.Research Design and MethodsWe used data from the New York City ED syndromic surveillance system during December 30, 2018 through May 21, 2022. This system captures all visits from EDs in the city in near-real time. We matched these visits to laboratory confirmed COVID-19 positivity data beginning with February 15, 2020.ResultsCompared to pre-pandemic baseline levels, diabetes related ED visits noticeably increased during the first wave in spring 2020, though this did not necessarily translate to net increases overall during that period. Visits for diabetic ketoacidosis, particularly among adults with type 2 diabetes, sharply increased before returning to pre-pandemic levels, most notably during wave 1 and wave 4 in winter 2021-2022. Trajectories of diabetes-related ED visits differed by diabetes type, age, and sex. Some ED visit trends did not return to pre-pandemic baseline levels.ConclusionsThe COVID-19 pandemic, especially the first wave in the spring of 2020, coincided with a dramatic shift in diabetes related ED utilization in New York City. Our findings highlight the importance of on-going surveillance of health care utilization for chronic diseases during population-level emergencies like pandemics. A robust syndromic surveillance system that includes infectious and non-infectious syndromes is useful to better prepare, mitigate, and respond to population-level events.Article HighlightsDiabetes related emergency department (ED) visits in New York City increased dramatically with the emergence of the COVID-19 pandemic in spring 2020.The trajectory of diabetes-related ED visits differed by diabetes type, age, sex, and pandemic wave.The diabetes complication of diabetic ketoacidosis among adults with type 2 diabetes showed sharp increases in the first and fourth waves of the pandemic, respectively its initial emergence in spring 2020 and the Omicron variant in winter 2021-2022.Our findings highlight the importance of on-going surveillance of health care utilization for chronic diseases during population-level emergencies like pandemics.SummaryData from NYC’s syndromic surveillance system showed major increases in #type2diabetes complications (e.g. diabetic ketoacidosis) during #COVID-19 waves 1 and 4 (Omicron) – this tool may be useful for population-level monitoring of chronic disease complications during emergencies
Imputation of structural variants using a multi-ancestry long-read sequencing panel enables identification of disease associations
Authors: Noyvert Boris , Mesut Erzurumluoglu A , Drichel Dmitriy , Omland Steffen , Andlauer Till F M , Mueller Stefanie , Sennels Lau , Becker Christian , Kantorovich Aleksandr , Bartholdy Boris A , Brænne Ingrid , Bolivar-Lopez Julio Cesar , Mistrellides Costas , Belbin Gillian M , Li Jeremiah H , Pickrell Joseph K , Arora Jatin , Hu Yao ,   Boehringer Ingelheim – Global Computational Biology and Digital Sciences, Wood Clive R , Kriegl Jan M , Podduturi Nikhil , Jensen Jan N , Stutzki Jan , Ding Zhihao 
Published: December 2023

AbstractAdvancements in long-read sequencing technology have accelerated the study of large structural variants (SVs). We created a curated, publicly available, multi-ancestry SV imputation panel by long-read sequencing 888 samples from the 1000 Genomes Project. This high-quality panel was used to impute SVs in approximately 500,000 UK Biobank participants. We demonstrated the feasibility of conducting genome-wide SV association studies at biobank scale using 32 disease-relevant phenotypes related to respiratory, cardiometabolic and liver diseases, in addition to 1,463 protein levels. This analysis identified thousands of genome-wide significant SV associations, including hundreds of conditionally independent signals, thereby enabling novel biological insights. Focusing on genetic association studies of lung function as an example, we demonstrate the added value of SVs for prioritising causal genes at gene-rich loci compared to traditional GWAS using only short variants. We envision that future post-GWAS gene-prioritisation workflows will incorporate SV analyses using this SV imputation panel and framework.
Identifying individuals with rare disease variants by inferring shared ancestral haplotypes from SNP array data
Authors: Robertson Erandee , Grinton Bronwyn E , Oliver Karen L , Fearnley Liam G , Hildebrand Michael S , Sadleir Lynette G , Scheffer Ingrid E , Berkovic Samuel F , Bennett Mark F , Bahlo Melanie 
Published: December 2023

ABSTRACTWe describe FoundHaplo, a novel identity-by-descent algorithm designed to identify individuals with known, untyped, disease-causing variants using only SNP array data. FoundHaplo leverages knowledge of shared disease haplotypes for inherited disease-causing variants to identify individuals who share the disease haplotype and are, therefore, likely to carry the rare (MAF<0.01) variant. We performed a simulation study to evaluate the performance of FoundHaplo across 33 known disease-harbouring loci. We demonstrated the ability of FoundHaplo to infer the presence of two rare (MAF<0.01) pathogenic variants,SCN1Bc.363C>G (p.Cys121Trp) andWWOXc.49G>A (p.E17K), which can cause mild dominant and severe recessive epilepsy respectively, in two large cohorts including 1,573 individuals with epilepsy from the Epi25 cohort and 468,481 individuals from the UK Biobank. We demonstrate that FoundHaplo performs substantially better at inferring the presence of these variants than existing genome-wide imputation approaches. FoundHaplo is a valuable, low-cost screening tool that can be applied to search SNP genotyping array data for disease-causing variants with known founder effects based on shared disease haplotypes. FoundHaplo is available athttps://github.com/bahlolab/FoundHaplo.
De novo design of diverse small molecule binders and sensors using Shape Complementary Pseudocycles
Authors: An Linna , Said Meerit , Tran Long , Majumder Sagardip , Goreshnik Inna , Lee Gyu Rie , Juergens David , Dauparas Justas , Anishchenko Ivan , Coventry Brian , Bera Asim K. , Kang Alex , Levine Paul M. , Alvarez Valentina , Pillai Arvind , Norn Christoffer , Feldman David , Zorine Dmitri , Hicks Derrick R. , Li Xinting , Sanchez Mariana Garcia , Vafeados Dionne K. , Salveson Patrick J. , Vorobieva Anastassia A. , Baker David 
Published: December 2023

AbstractA general method for designing proteins to bind and sense any small molecule of interest would be widely useful. Due to the small number of atoms to interact with, binding to small molecules with high affinity requires highly shape complementary pockets, and transducing binding events into signals is challenging. Here we describe an integrated deep learning and energy based approach for designing high shape complementarity binders to small molecules that are poised for downstream sensing applications. We employ deep learning generated psuedocycles with repeating structural units surrounding central pockets; depending on the geometry of the structural unit and repeat number, these pockets span wide ranges of sizes and shapes. For a small molecule target of interest, we extensively sample high shape complementarity pseudocycles to generate large numbers of customized potential binding pockets; the ligand binding poses and the interacting interfaces are then optimized for high affinity binding. We computationally design binders to four diverse molecules, including for the first time polar flexible molecules such as methotrexate and thyroxine, which are expressed at high levels and have nanomolar affinities straight out of the computer. Co-crystal structures are nearly identical to the design models. Taking advantage of the modular repeating structure of pseudocycles and central location of the binding pockets, we constructed low noise nanopore sensors and chemically induced dimerization systems by splitting the binders into domains which assemble into the original pseudocycle pocket upon target molecule addition.One Sentence SummaryWe use a pseuodocycle-based shape complementarity optimizing approach to design nanomolar binders to diverse ligands, including the flexible and polar methotrexate and thyroxine, that can be directly converted into ligand-gated nanopores and chemically induced dimerization systems.
The promise and peril of comparing fluorescence lifetime in biology revealed by simulations
Authors: Ma Pingchuan , Sternson Scott , Chen Yao 
Published: December 2023

AbstractSignaling dynamics are crucial in biological systems, and biosensor-based real-time imaging has revolutionized their analysis. Fluorescence lifetime imaging microscopy (FLIM) excels over the widely used fluorescence intensity imaging by allowing the measurement of absolute signal levels, independent of sensor concentration. This capability enables the comparison of signaling dynamics across different animals, body regions, and timeframes. However, FLIM’s advantage can be compromised by factors like autofluorescence in biological experiments. To address this, we introduce FLiSimBA, a flexible computational framework for realisticFluorescenceLifetimeSimulation forBiologicalApplications. Through simulations, we analyze the signal-to-noise ratios of fluorescence lifetime data, determining measurement uncertainty and providing necessary error bars for lifetime measurements. Furthermore, we challenge the belief that fluorescence lifetime is unaffected by sensor expression and establish quantitative limits to this insensitivity in biological applications. Additionally, we propose innovations, notably multiplexed dynamic imaging that combines fluorescence intensity and lifetime measurements. This innovation can transform the number of signals that can be simultaneously monitored, thereby enabling a systems approach in studying signaling dynamics. Thus, by incorporating diverse factors into our simulation framework, we uncover surprises, identify limitations, and propose advancements for fluorescence lifetime imaging in biology. This quantitative framework supports rigorous experimental design, facilitates accurate data interpretation, and paves the way for technological advancements in fluorescence lifetime imaging.
Hemolymph transfusions transfer heritable learned novel odor preferences to naïve larvae ofBicyclus anynanabutterflies
Authors: Gowri V. , Monteiro Antónia 
Published: December 2023

AbstractThe mechanisms whereby environmental experiences of parents are transmitted to their offspring to impact their behavior and fitness are poorly understood. Previously, we showed that naïveBicyclus anynanabutterfly larvae, whose parents fed on a normal plant feed but coated with a novel odor, inherited a learned preference towards that odor, which had initially elicited avoidance in the naïve parents. Here, we performed simple hemolymph transfusions from odor-fed and control-fed larvae to naïve larval recipients. We found that larvae injected with hemolymph from odor-fed donors stopped avoiding the novel odor, and their naïve offspring preferred the odor more, compared to the offspring of larvae injected with control hemolymph. These results indicate that factors in the hemolymph, potentially the odor molecule itself, play an important role in odor learning and preference transmission across generations. Furthermore, this mechanism of odor preference inheritance, mediated by the hemolymph, bypasses the peripheral odor-sensing mechanisms taking place in the antennae, mouthparts, or legs, and may mediate host plant switching and diversification in the Lepidoptera or more broadly across insects.
e- Health for Fighting Digital Addiction: a Literature Review
Authors: Nurrahima Artika , Pandin Moses Glorino Rumambo , Yusuf Ah. 
Published: December 2023

ABSTRACTBackgroundThe internet highly used worldwide triggers addiction to technology at various age stages. Digital addiction has various negative impacts on health, social, economic, and educational aspects. Various recent studies explained the influence of technology-based interventions to prevent and overcome digital addiction, which indirectly reduced the negative impact of addiction. The purpose of this study was to analyze the use of e-health in various age ranges, the type of e-health used and the type of intervention that uses e-health as a media for fighting digital addiction.MethodThis study is a literature review related to e-health intervention in digital addiction obtained from data bases: SpringerLink, ScienceDirect, ProQues, Ebsco CINAHL, and Google scholar with keywords and booleans: “internet addiction” OR “smartphone addiction” OR “game addiction” AND therapy OR intervention AND “e-health” OR “digital health” OR “digital intervention” OR “digital education. Articles in this review are limited to English articles from 2020-2023. The PRISMA guidline is used as a reference protocol and evaluation of literature review.ResultBased on the 11 articles included in this review, e-health interventions are used as strategy to prevent and treat digital addiction in children, adolescents and adults. The majority of the population who use e-health are adolescents. The type of e-health used as the main intervention was smartphone apps, while game was used as additional intervention. The majority of interventions that can be delivered through e-health are CBT based, while other interventions are behavior monitoring and nudge based.ConclusionE-health intervention can be used as the main and additional intervention to prevent and overcome digital addiction in various ages, especially adolescents, tend to have a high success rate. The development of e-health can be seen as a promising intervention to facilitate healthy digital behavior change.
Automated workflow for the cell cycle analysis of (non-)adherent cells using a machine learning approach
Authors: Hayatigolkhatmi Kourosh , Soriani Chiara , Soda Emanuel , Ceccacci Elena , Menna Oualid El , Peri Sebastiano , Negrelli Ivan , Bertolini Giacomo , Franchi Gian Martino , Carbone Roberta , Minucci Saverio , Rodighiero Simona 
Published: December 2023

SummaryUnderstanding the details of the cell cycle at the level of individual cells is critical for both cellular biology and cancer research. While existing methods using specific fluorescent markers have advanced our ability to study the cell cycle in cells that adhere to surfaces, there is a clear gap when it comes to non-adherent cells. In this study, we combine a specialized surface to improve cell attachment, the genetically-encoded FUCCI(CA)2 sensor, an automated image processing and analysis pipeline, and a custom machine-learning algorithm. This combined approach allowed us to precisely measure the duration of different cell cycle phases in non-adherent cells.Our method provided detailed information from hundreds of cells under different experimental conditions in a fully automated manner. We validated this approach in two different Acute Myeloid Leukemia (AML) cell lines, NB4 and Kasumi-1, which have unique cell cycle characteristics. Additionally, we tested the impact of drugs affecting the cell cycle in NB4 cells. Importantly, our cell cycle analysis system is freely available and has also been validated for use with adherent cells.In summary, this report introduces a comprehensive, automated method for studying the cell cycle in both adherent and non-adherent cells, offering a valuable tool for cancer research and drug development.
Agarose disk electroporation method forex vivoretinal tissue cultured at the air-liquid interface reveals electrical stimulus-induced cell cycle reentry in retinal cells
Authors: Stone Megan L. , Lee Hannah H. , Levine Edward M. 
Published: December 2023

SummaryIt is advantageous to culture theex vivomurine retina along with many other tissue types at the air-liquid interface. However, gene delivery to these cultures can be challenging. Electroporation is a fast and robust method of gene delivery, but typically requires submergence in a liquid buffer to allow electric current flow. We have developed a submergence-free electroporation technique using that allows for efficient gene delivery to theex vivomurine retina. This method advances our ability to useex vivoretinal tissue for genetic studies and can easily be adapted for any tissue cultured at an air-liquid interface. Use of this method has revealed valuable insights on the state ofex vivoretinal tissues and the effects of electrical stimulation on retinal cells.MotivationTissues cultured at the air-liquid interface, such as retinal tissue, are adhered to a filter membrane with media underneath but not fully submerged. If tissues are fully submerged in liquid, they detach from the membrane and become damaged. Electroporation typically requires tissue submergence for electric current flow. We have developed a submergence-free electroporation method using an agarose disk for electric current delivery that can efficiently and consistently electroporateex vivoretinal tissue cultured at an air-liquid interface without the need to submerge the tissue and disrupt the culture system.
CUL-6/cullin ubiquitin ligase-mediated degradation of HSP-90 by intestinal lysosomes promotes thermotolerance
Authors: Sarmiento Mario Bardan , Gang Spencer S. , van Oosten-Hawle Patricija , Troemel Emily R. 
Published: December 2023

AbstractHeat shock can be a lethal stressor. Previously, we described a CUL-6/cullin-ring ubiquitin ligase complex in the nematodeCaenorhabditis elegansthat is induced by intracellular intestinal infection and proteotoxic stress, and that promotes improved survival upon heat shock (thermotolerance). Here, we show that CUL-6 promotes thermotolerance by targeting the heat shock protein HSP-90 for degradation. We show that CUL-6-mediated lowering of HSP-90 protein levels, specifically in the intestine, provides a thermotolerance benefit independent of heat shock factor HSF-1. Furthermore, we show that lysosomal function is required for CUL-6-mediated promotion of thermotolerance and that CUL-6 directs HSP-90 to lysosome-related organelles upon heat shock. Altogether, these results indicate that a CUL-6 ubiquitin ligase promotes organismal survival upon heat shock by promoting HSP-90 degradation in intestinal lysosomes. Thus, HSP-90, a protein commonly associated with protection against heat shock and promoting degradation of other proteins, is actually itself degraded to protect against heat shock.
Identification of a Novel Ferroptosis Inducer with Dual Modulatory Effects on GPX4 Activity and Stability
Authors: Wang Jun , Liao Long , Yang Bo , Miao Beiping , Li Botai , Ma Xuhui , Fitz Annika , Wu Shanshan , He Jia , Zhang Qianqian , Ji Shuyi , Jin Guangzhi , Zhang Jianming , Bernards René , Qin Wenxin , Sun Chong , Wang Cun 
Published: December 2023

AbstractFerroptosis is a unique form of intracellular iron-dependent cell death that differs from apoptosis, necrosis, and autophagy. GPX4, an antioxidant defense enzyme, plays a pivotal role as regulator of ferroptosis. Extensive researches suggest that targeting GPX4 holds promise for cancer therapy. However, the current GPX4 inhibitors face challenges due to unfavorable drug-like properties, which hinder their progress in clinical development. In this study, we identified a novel inhibitor called MI-2, demonstrating potent ferroptosis-inducing capacity. Mechanistically, MI-2 effectively inhibits the activity of GPX4 by direct interaction. Furthermore, MI-2 promotes the degradation of GPX4 through its well-established target, MALT1. In multiple cancer models, MI-2 has demonstrated synergistic effects when combined with sorafenib or regorafenib, resulting in enhanced ferroptosis induction. These findings highlight the dual modulatory effects of MI-2 on GPX4 activity and stability, offering a promising starting point for the development of drug-like GPX4 inhibitors with translational potential.