bluuebunny/crossref_metadata_2025_split huggingface dataset:
Training the next generation of physician-scientists: a cohort-based program for MD-only residents and fellows
Authors: Solvik Tina A. , Schnoes Alexandra M. , Nguyen Thi A. , Behrman Shannon L. , Maksoud Elie , Goodwin Sarah S. , Weiss Ethan J. , Padmanabhan Arun , Cornfield David N. 
Published: December 2022

AbstractImportanceDespite the importance of clinician-scientists in propelling biomedical advances, the proportion of physicians engaged in both hypothesis-driven research and clinical care continues to decline. Recently, multiple institutions have developed programs that promote MD-only physicians pursuing careers in science, but few reports on the impact of these are available.ObjectiveTo assess if a cohort-based training program for MD-only physician-scientists that includes didactic and experiential curricula favorably informs participants’ scientific development.DesignThe Chan Zuckerberg Biohub (CZB) Physician-Scientist Fellowship Program (PSFP) conducted a study from July 2020 to August 2023.Participants24 inaugural program participants at UCSF and Stanford University (median postgraduate year at program start, 5.5; 17 clinical specialties represented; 10 [42%] identified as female; 7 [29%] identified as underrepresented in medicine).ExposuresThe CZB PSFP is a selective two-year career development program for MD-only physicians. Participants attended a two-week immersive training at the program outset, and subsequently, weekly curricular and scientific meetings throughout the program while conducting research.Main Outcomes and MeasuresPrimary outcome measurements included pre-, 1-month, and 12-month assessments of confidence in research skills, career skills, and self-identification as scientists. Program satisfaction and feedback related to program curriculum and community were collected at 1 month, 6 months, and 12 months.ResultsAfter 12 months, 100% (N=16) reported satisfaction with the program and participants demonstrated increased confidence in research skills [median (IQR), 4.0 (2.5-5.0) pre-bootcamp to 5.5 (4.0-6.0) 12-mo], career skills significantly increased [median (IQR), 4.0 (4.0-5.0) pre-bootcamp to 5.5 (5.0-6.0) 12-mo], perceptions of belonging significantly increased [median (IQR), 4.0 (2.5-5.4) pre-bootcamp to 5.5 (5.1-7.0) 12-mo], and scientific identity significantly increased [median (IQR), 5.0 (4.0-5.5) pre-bootcamp to 6.0 (5.5-7.0) 12-mo].Conclusion and RelevanceParticipants demonstrated significant gains in confidence in core research and career skills as well as personal identification as scientists, demonstrating the efficacy of a longitudinal curriculum, peer support, and community building in fostering development as an investigator. The highly portable nature of this strategy may facilitate ready adoption and implementation at other institutions.
coronabambini.ch: Development and usage of an online decision support tool for pediatric COVID-testing in Switzerland: a cross-sectional analysis
Authors: Starvaggi C , Travaglini N , Aebi C , Romano F , Steiner I , Sauter T C , Keitel K 
Published: December 2022

AbstractObjectivesTo describe the development and usage of coronabambini.ch as an example of a pediatric electronic public health application and to explore its potential and limitations in providing information on disease epidemiology and public health policy implementation.DesignWe developed and maintained a non-commercial online decision support tool, coronabambini.ch, to translate the Swiss FOPH pediatric (age 0-18 years) COVID-19 guidelines around testing and school/daycare attendance for caregivers, teachers, and healthcare personnel. We analyzed the online decision tool as well as a voluntary follow-up survey from October 2020 to September 2021 to explore its potential as a surveillance tool for public health policy and epidemiology.Participants68’269 users accessed and 52’726 filled out the complete online decision tool. 3% (1’399/52’726) filled out a voluntary follow-up. 92% (18’797/20’330) of users were parents.ResultsCertain dynamics of the pandemic and changes in testing strategies were reflected in the data captured by coronabambini.ch: e.g. in terms of disease epidemiology, gastrointestinal symptoms were reported more frequently in younger age-groups (13% (3’308/26’180) in children 0-5 years versus 9% (3’934/42’089) in children ≥6 years, 𝒳2=184,P=<.001). As a reflection of public health policy, the proportion of users consulting the tool for a positive contact without symptoms in children 6-12 years increased from 4% (1’415/32’215) to 6% (636/9’872) after the FOPH loosened testing criteria in this age-group, 𝒳2=69,P=<.001. Adherence to the recommendation was generally high (84% (1’131/1’352)) but differed by the type of recommendation: 89% (344/385) for “stay at home and observe”, 75% (232/310) for “school attendance”.ConclusionsUsage of coronabambini.ch was generally high in areas where it was developed and promoted. Certain patterns in epidemiology and adherence to public health policy could be depicted but selection bias was difficult to measure showing the potential and challenges of digital decision support as public health tools.Strengths and limitations of this studyWe developed and maintained a non-commercial online decision support tool, coronabambini.ch, based on the Swiss Federal Office of Public Health (FOPH) pediatric COVID-19 guidelines around testing and school/daycare attendance.We performed a descriptive analysis of the usage data from the tool between October 2020 to September 2021 to explore its potential as a surveillance tool for public health policy and epidemiology.A follow-up survey measured comprehensibility and adherence of the online decision tool.The types of selection biases of the data were difficult to assess within this voluntary online survey system.Response rate of the follow-up survey was low and participants with high education and high health literacy were overrepresented.
The Canadian Food Intake Screener for assessing alignment of adults’ dietary intake with the 2019 Canada’s Food Guide healthy food choices recommendations: Scoring system and construct validity
Authors: Hutchinson Joy M. , Dodd Kevin W. , Guenther Patricia M. , Lamarche Benoit , Haines Jess , Wallace Angela , Perreault Maude , Williams Tabitha E. , Costa Louzada Maria Laura da , Jessri Mahsa , Lemieux Simone , Olstad Dana Lee , Prowse Rachel , Simpson Janis Randall , Vena Jennifer E. , Szajbely Kathleen , Kirkpatrick Sharon I. 
Published: December 2022

AbstractThe Canadian Food Intake Screener/Questionnaire court canadien sur les apports alimentaires was developed to rapidly assess alignment of adults’ dietary intake over the past month with the 2019 Canada Food Guide’s healthy food choices recommendations. From July to December 2021, adults (n=154) aged 18-65 years completed the screener and up to two 24-hour dietary recalls. The screener scoring system was aligned with the Healthy Eating Food Index-2019 (HEFI-2019), to the extent possible. ANOVA compared screener scores among subgroups with known differences in diet quality. Using the recall data, the National Cancer Institute multivariate method was used to model HEFI-2019 components, with the screener score as a covariate, and the correlation coefficient between screener and total HEFI-2019 scores was estimated. The mean screener score was 35 points (SD=4.7; maximum, 65), ranging from 25 (1stpercentile) to 45 (99thpercentile). Differences in scores in hypothesized directions were evident by gender identity (p=0.06), perceived income adequacy (p=0.07), education (p=0.02), and smoking status (p=0.003). The correlation between screener and HEFI-2019 scores was 0.53 (SE=0.12). The screener’s moderate construct validity supports its use for rapid assessment of alignment of adults’ intake with the healthy food choices recommendations when comprehensive dietary assessment is not possible.NoveltyThe Canadian Food Intake Screener was developed to rapidly assess alignment of dietary intake with Canada’s Food Guide-2019 healthy food choices recommendations.Scoring is aligned with the Healthy Eating Food Index-2019, to the extent possible.Among a sample of adults, variation in screener scores was noted, mean screener scores differed between some subgroups with known differences in diet quality, and a moderate correlation between screener scores and total Healthy Eating Food Index-2019 scores based on repeat 24-hour dietary recalls was observed.The Canadian Food Intake Screener has moderate construct validity for rapid assessment of overall alignment of adults’ dietary intake with the Canada’s Food Guide-2019 healthy food choices recommendations when comprehensive dietary assessment is not possible.
Performance of ChatGPT on USMLE: Potential for AI-Assisted Medical Education Using Large Language Models
Authors: Kung Tiffany H. , Cheatham Morgan ,   ChatGPT, Medenilla Arielle , Sillos Czarina , De Leon Lorie , Elepaño Camille , Madriaga Maria , Aggabao Rimel , Diaz-Candido Giezel , Maningo James , Tseng Victor 
Published: December 2022

ABSTRACTWe evaluated the performance of a large language model called ChatGPT on the United States Medical Licensing Exam (USMLE), which consists of three exams: Step 1, Step 2CK, and Step 3. ChatGPT performed at or near the passing threshold for all three exams without any specialized training or reinforcement. Additionally, ChatGPT demonstrated a high level of concordance and insight in its explanations. These results suggest that large language models may have the potential to assist with medical education, and potentially, clinical decision-making.
Annotation and Information Extraction of a Consumer-Friendly Health Website for Enhancing Laboratory Test Reporting in Patient Portals
Authors: He Zhe , Tian Shubo , Erdengasileng Arslan , Hanna Karim , Gong Yang , Zhang Zhan , Luo Xiao , Lustria Mia Liza A. 
Published: December 2022

AbstractViewing laboratory test results is patients’ most frequent activity when accessing patient portals, but lab results can be very confusing for patients. Previous research has explored various ways to present lab results, but few have attempted to provide tailored information support based on individual patient’s medical context. In this study, we collected and annotated interpretations of textual lab result in 251 health articles about laboratory tests from AHealthyMe.com. Then we evaluated transformer-based language models including BioBERT, ClinicalBERT, RoBERTa, and PubMedBERT for recognizing key terms and their types. Using BioPortal’s term search API, we mapped the annotated terms to concepts in major controlled terminologies. Results showed that PubMedBERT achieved the best F1 on both strict and lenient matching criteria. SNOMED CT had the best coverage of the terms, followed by LOINC and ICD-10-CM. This work lays the foundation for enhancing the presentation of lab results in patient portals by providing patients with contextualized interpretations of their lab results and individualized question prompts that they can, in turn, refer to during physician consults.
Clinical prediction rule to guide diagnostic testing forShigellosisand improve antibiotic stewardship for pediatric diarrhea
Authors: Ahmed Sharia M. , Brintz Ben J. , Pavlinac Patricia B. , Hossain Md Iqbal , Khan Ashraful Islam , Platts-Mills James A. , Kotloff Karen L. , Leung Daniel T. 
Published: December 2022

ABSTRACTBackgroundDiarrheal diseases are a leading cause of death for children under-5.Identification of etiology helps guide pathogen-specific therapy, but availability of diagnostic testing is often limited in low resource settings. Our goal is to develop a clinical prediction rule (CPR) to guide clinicians in identifying when to use a point-of-care diagnostic forShigellain children presenting with acute diarrhea.MethodsWe used clinical and demographic data from the Global Enteric Multicenter Study (GEMS) study to build predictive models for diarrhea ofShigellaetiology in children ≤59 months presenting with moderate-to-severe diarrhea in Africa and Asia. We screened variables using random forests, and assessed predictive performance with random forest regression and logistic regression using cross-validation. We used the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study to externally validate our GEMS-derived CPR.ResultsOf the 5011 cases analyzed, 1332 (27%) had diarrhea ofShigellaetiology. Our CPR had high predictive ability (AUC=0.80 (95% CI: 0.79, 0.81) using the top two predictive variables, age and caregiver reported bloody diarrhea. We show that by using our CPR to triage who receives diagnostic testing, 3 times moreShigelladiarrhea cases would have been identified compared to current symptom-based guidelines, with only 27% of cases receiving a point-of-care diagnostic test.ConclusionsWe demonstrate how a clinical prediction rule can be used to guide use of a point-of-care diagnostic test for diarrhea management. Using our CPR, available diagnostic capacity can be optimized to improve appropriate antibiotic use.Key pointsUsing an externally validated clinical prediction tool to triage who receives diagnostic testing, 3 times moreShigelladiarrhea cases would have been identified compared to current symptom-based guidelines, with only 27% of cases receiving a point-of-care diagnostic test.
The convergence and divergence of spontaneous brain activity of humans and marmosets
Authors: Zhang Jinbo 
Published: December 2022

AbstractThe brain at rest or during periods of relative inactivity, complex dynamical patterns of activity spontaneously form over the entire brain. In this study, we plan to clarify the convergence and divergence of spontaneous brain activity across humans and marmosets. We investigated the spontaneous brain dynamics of marmosets, and compared its convergence and divergence with human neuroimaging results. We identified seven representative FC patterns (FC states) in the resting-state activity of marmosets. The most prevalent two FC patterns (VC1 and VC2) corresponds to a state of BOLD coherence of primary visual and auditory processing regions. Our results suggested that the spontaneous activity does reflect the inherent properties of the brain of marmosets.
Multi-location trials and population-based genotyping reveal high diversity and adaptation to breeding environments in a large collection of red clover
Authors: Nay Michelle M. , Grieder Christoph , Frey Lea A. , Amdahl Helga , Radovic Jasmina , Jaluvka Libor , Palmé Anna , Skøt Leif , Ruttink Tom , Kölliker Roland 
Published: December 2022

AbstractRed clover (Trifolium pratenseL.) is an outcrossing forage legume that has adapted to a wide range of climatic and growing conditions across Europe. Red clover is valued for its high yield potential and forage quality. The high amount of genetic diversity present in red clover provides an invaluable, but often poorly characterized resource to improve key traits such as yield, quality, and resistance to biotic and abiotic stresses. In this study, we examined the genetic and phenotypic diversity within a diverse set of 395 diploid red clover accessions via genome wide allele frequency fingerprinting and multi-location field trials across Europe. We found that the genetic structure of accessions mostly reflected their geographic origin and only few cases were detected, where breeders integrated foreign genetic resources into their local breeding pools. Phenotypic performance of accessions in the multi-location field trials revealed a very strong accession x location interaction. Notably, breeding material and cultivars generally performed well at the location where they were developed. Local adaptation was especially prominent in Nordic red clover accessions that showed a distinct adaptation to the growing conditions and cutting regime of the North. Our results confirmed that red clover cultivars were bred from regional ecotypes and show a narrow adaptation to regional conditions. Our study can serve as a valuable basis for identifying interesting material that express the desired characteristics and contribute to the adaptation of red clover to future climatic conditions.
Targeted Protein Degradation through E2 Recruitment
Authors: Forte Nafsika , Dovala Dustin , Hesse Matthew J. , McKenna Jeffrey M. , Tallarico John A. , Schirle Markus , Nomura Daniel K. 
Published: December 2022

AbstractTargeted protein degradation (TPD) with Proteolysis Targeting Chimeras (PROTACs), heterobifunctional compounds consisting of protein targeting ligands linked to recruiters of E3 ubiquitin ligases, has arisen as a powerful therapeutic modality to induce the proximity of target proteins with E3 ligases to ubiquitinate and degrade specific proteins in cells. Thus far, PROTACs have primarily exploited the recruitment of E3 ubiquitin ligases or their substrate adapter proteins but have not exploited the recruitment of more core components of the ubiquitin-proteasome system (UPS). In this study, we used covalent chemoproteomic approaches to discover a covalent recruiter against the E2 ubiquitin conjugating enzyme UBE2D—EN67—that targets an allosteric cysteine, C111, without affecting the enzymatic activity of the protein. We demonstrated that this UBE2D recruiter could be used in heterobifunctional degraders to degrade neo-substrate targets in a UBE2D-dependent manner, including BRD4 and the androgen receptor. Overall, our data highlight the potential for the recruitment of core components of the UPS machinery, such as E2 ubiquitin conjugating enzymes, for TPD, and underscore the utility of covalent chemoproteomic strategies for identifying novel recruiters for additional components of the UPS.
Golgi retention and oncogenic KIT signaling via PLCγ2-PKD2-PI4KIIIβ activation in GIST cells
Authors: Obata Yuuki , Kurokawa Kazuo , Tojima Takuro , Natsume Miyuki , Shiina Isamu , Takahashi Tsuyoshi , Abe Ryo , Nakano Akihiko , Nishida Toshirou 
Published: December 2022

SUMMARYMost gastrointestinal stromal tumors (GISTs) develop due to gain-of-function mutations in the tyrosine kinase,KIT. We recently showed that mutant KIT mislocalizes to the Golgi area and initiates uncontrolled signaling. However, the molecular mechanisms underlying its Golgi retention remain unknown. Here, we show that protein kinase D2 (PKD2) is activated by the mutant, which causes KIT’s Golgi retention. In PKD2-inhibited cells, KIT migrates from the Golgi region to lysosomes and subsequently undergoes degradation. Importantly, delocalized KIT is unable to trigger downstream activation. In the Golgi area, KIT activates the PKD2-phosphatidylinositol 4-kinaseIIIβ (PKD2-PI4KIIIβ) pathway through phospholipase γ2 (PLCγ2) to generate a PI4P-rich membrane domain, where the AP1-GGA1 complex is aberrantly recruited. Disruption of any factors in this cascade results in KIT release from the Golgi region, indicating that these PKD2-related pathways are responsible for the Golgi retention of KIT. Our findings unveil the molecular mechanisms underlying KIT mislocalization and provide evidence for a new strategy for inhibition of oncogenic signaling.
Probing the evolutionary dynamics of whole-body regeneration within planarian flatworms
Authors: Vila-Farré Miquel , Rozanski Andrei , Ivanković Mario , Cleland James , Brand Jeremias N. , Thalen Felix , Grohme Markus , von Kannen Stephanie , Grosbusch Alexandra , Vu Han T-K , Prieto Carlos E. , Carbayo Fernando , Egger Bernhard , Bleidorn Christoph , Rasko John E. J. , Rink Jochen C. 
Published: December 2022

AbstractWhy some animals can regenerate while many others cannot remains a fascinating question. Even amongst planarian flatworms, well-known for their ability to regenerate complete animals from small body fragments, species exist that have restricted regeneration abilities or are entirely regeneration incompetent. Towards the goal of probing the evolutionary dynamics of regeneration, we have assembled a diverse live collection of planarian species from around the world. The combined quantification of species-specific head regeneration abilities and comprehensive transcriptome-based phylogeny reconstructions reveals multiple independent transitions between robust whole-body regeneration and restricted regeneration in the freshwater species. Our demonstration that theRNAi-mediated inhibition of canonical Wnt signalling can nevertheless bypass all experimentally tractable head regeneration defects in the current collection indicates that the pathway may represent a hot spot in the evolution of planarian regeneration defects. Combined with our finding that Wnt signalling has multiple roles in the reproductive system of the model speciesS. mediterranea, this raises the possibility of a trade-off between egg-laying and asexual reproduction by fission/regeneration as a driver of regenerative trait evolution. Although initial quantitative comparisons of Wnt signalling levels, reproductive investment, and regenerative abilities across the collection confirm some of the model’s predictions, they also highlight the diversification of molecular mechanisms amongst the divergent planarian lineages. Overall, our study establishes a framework for the mechanistic evolution of regenerative abilities and planarians as model taxon for comparative regeneration research.
Diclofenac and other Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are Competitive Antagonists of the human P2X3 Receptor
Authors: Grohs Laura , Cheng Linhan , Cönen Saskia , Haddad Bassam G. , Obrecht Astrid , Toklucu Idil , Ernst Lisa , Körner Jannis , Schmalzing Günther , Lampert Angelika , Machtens Jan-Philipp , Hausmann Ralf 
Published: December 2022

AbstractThe P2X3 receptor (P2X3R), an ATP-gated non-selective cation channel of the P2X receptor family, is expressed in sensory neurons and involved in nociception. P2X3R inhibition was shown to reduce chronic and neuropathic pain. In a previous screening of 2000 approved drugs, natural products and bioactive substances, various non-steroidal anti-inflammatory drugs (NSAIDs) were found to inhibit P2X3R-mediated currents. To investigate whether the inhibition of P2X receptors contributes to the analgesic effect of NSAIDs, we characterized the potency and selectivity of various NSAIDs at P2X3R and other P2XR subtypes using two-electrode voltage clamp electrophysiology. We identified diclofenac as a hP2X3R and hP2X2/3R antagonist with micromolar potency (with IC50values of 138.2 µM and 76.7 µM, respectively). A weaker inhibition of hP2X1R, hP2X4R and hP2X7R by diclofenac was determined. Flufenamic acid (FFA) proved to inhibit hP2X3R, rP2X3R and hP2X7R (IC50values of 221µM, 264.1µM and ∼ 900µM, respectively), questioning its widespread use as a nonselective ion channel blocker, when P2XR-mediated currents are under study.Inhibition of the hP2X3R or hP2X2/3R by diclofenac could be overcome by prolonged ATP-application or increasing concentrations of the agonist α,β-meATP, respectively, indicating competition of diclofenac and the agonists. Molecular dynamics simulation showed that diclofenac largely overlaps with ATP bound to the open state of the hP2X3R. Our results strongly support a competitive antagonism through which diclofenac, by interacting with residues of the ATP-binding site, left flipper, and dorsal fin domains inhibits gating of P2X3R by conformational fixation of the left flipper and dorsal fin domains.In summary, we demonstrate the inhibition of the human P2X3 receptor by various NSAIDs. Diclofenac proved to be the most effective antagonist with a strong inhibition of hP2X3R and hP2X2/3R and a weaker inhibition of hP2X1R, hP2X4R and hP2X7R. Considering their involvement in nociception, inhibition of hP2X3R and hP2X2/3R by micromolar concentrations of diclofenac may contribute to the analgesic effect as well as the side effect of taste disturbances of diclofenac and represent an additional mode of action besides the well-known high potency COX inhibition.