bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthetic Health Data Can Augment Community Research Efforts to Better Inform the Public During Emerging Pandemics
Authors: Prasanna Anish , Jing Bocheng , Plopper George , Miller Kristina Krasnov , Sanjak Jaleal , Feng Alice , Prezek Sarah , Vidyaprakash Eshaw , Thovarai Vishal , Maier Ezekiel J. , Bhattacharya Avik , Naaman Lama , Stephens Holly , Watford Sean , John Boscardin W. , Johanson Elaine , Lienau Amanda 
Published: December 2023

ABSTRACTThe COVID-19 pandemic had disproportionate effects on the Veteran population due to the increased prevalence of medical and environmental risk factors. Synthetic electronic health record (EHR) data can help meet the acute need for Veteran population-specific predictive modeling efforts by avoiding the strict barriers to access, currently present within Veteran Health Administration (VHA) datasets. The U.S. Food and Drug Administration (FDA) and the VHA launched the precisionFDA COVID-19 Risk Factor Modeling Challenge to develop COVID-19 diagnostic and prognostic models; identify Veteran population-specific risk factors; and test the usefulness of synthetic data as a substitute for real data. The use of synthetic data boosted challenge participation by providing a dataset that was accessible to all competitors. Models trained on synthetic data showed similar but systematically inflated model performance metrics to those trained on real data. The important risk factors identified in the synthetic data largely overlapped with those identified from the real data, and both sets of risk factors were validated in the literature. Tradeoffs exist between synthetic data generation approaches based on whether a real EHR dataset is required as input. Synthetic data generated directly from real EHR input will more closely align with the characteristics of the relevant cohort. This work shows that synthetic EHR data will have practical value to the Veterans’ health research community for the foreseeable future.
ChatGPT for automating lung cancer staging: feasibility study on open radiology report dataset
Authors: Nakamura Yuta , Kikuchi Tomohiro , Yamagishi Yosuke , Hanaoka Shouhei , Nakao Takahiro , Miki Soichiro , Yoshikawa Takeharu , Abe Osamu 
Published: December 2023

AbstractObjectivesCT imaging is essential in the initial staging of lung cancer. However, free-text radiology reports do not always directly mention clinical TNM stages. We explored the capability of OpenAI’s ChatGPT to automate lung cancer staging from CT radiology reports.MethodsWe used MedTxt-RR-JA, a public de-identified dataset of 135 CT radiology reports for lung cancer. Two board-certified radiologists assigned clinical TNM stage for each radiology report by consensus. We used a part of the dataset to empirically determine the optimal prompt to guide ChatGPT. Using the remaining part of the dataset, we (i) compared the performance of two ChatGPT models (GPT-3.5 Turbo and GPT-4), (ii) compared the performance when the TNM classification rule was or was not presented in the prompt, and (iii) performed subgroup analysis regarding the T category.ResultsThe best accuracy scores were achieved by GPT-4 when it was presented with the TNM classification rule (52.2%, 78.9%, and 86.7% for the T, N, and M categories). Most ChatGPT’s errors stemmed from challenges with numerical reasoning and insufficiency in anatomical or lexical knowledge.ConclusionsChatGPT has the potential to become a valuable tool for automating lung cancer staging. It can be a good practice to use GPT-4 and incorporate the TNM classification rule into the prompt. Future improvement of ChatGPT would involve supporting numerical reasoning and complementing knowledge.Clinical relevance statementChatGPT’s performance for automating cancer staging still has room for enhancement, but further improvement would be helpful for individual patient care and secondary information usage for research purposes.Key pointsChatGPT, especially GPT-4, has the potential to automatically assign clinical TNM stage of lung cancer based on CT radiology reports.It was beneficial to present the TNM classification rule to ChatGPT to improve the performance.ChatGPT would further benefit from supporting numerical reasoning or providing anatomical knowledge.Graphical abstract
STAT4 Phosphorylation of T-helper Cells predicts surgical outcomes in Refractory Chronic Rhinosinusitis
Authors: Abidin Michael R. , Alpan Oral , Plassmeyer Matthew , Kozhaya Lina , Loizou Denise , Dogan Mikail , Upchurch Zachary , Manes Nathan P , Nita-Lazar Aleksandra , Unutmaz Derya , Sønder Søren Ulrik 
Published: December 2023

AbstractObjective: Chronic rhinosinusitis (CRS) impacts an estimated 5% to 15% of people worldwide, incurring significant economic healthcare burden. There is a urgent need for the discovery of predictive biomarkers to improve treatment strategies and outcomes for CRS patients.Study design: Cohort study of CRS patients and healthy controls using blood samples. Setting: Out-patient clinics.Methods: Whole blood samples were collected for flow cytometric analysis. Mechanistic studies involved the transfection of human primary T cells and Jurkat cells.Results: Our analysis began with a 63-69 year-old female patient diagnosed with refractory CRS,. Despite undergoing multiple surgeries, she continually faced sinus infections. Whole exome sequencing pinpointed a heterozygous IL-12Rb1 mutation situated in the linker region adjacent to the cytokine binding domain. When subjected to IL-12 stimulation, the patient’s CD4 T-cells exhibited diminished STAT4 phosphorylation. However, computer modeling or T-cell lines harboring the same IL-12 receptor mutation did not corroborate the hypothesis that IL-12Rb could be responsible for the reduced phosphorylation of STAT4 by IL-12 stimulation.Upon expanding our investigation to a broader CRS patient group using the pSTAT4 assay, we discerned a subset of refractory CRS patients with abnormally low STAT4 phosphorylation.The deficiency showed improvement both in-vitro and in-vivo after exposure toLatilactobacillus sakei(akaLactobacillus sakei), an effect at least partially dependent on IL-12.Conclusion: In refractory CRS patients, an identified STAT4 defect correlates with poor clinical outcomes after sinus surgery, which can be therapeutically targeted byLatilactobacillus sakeitreatment. Prospective double-blind placebo-controlled trials are needed to validate our findings.
Literature Review Interventions to Anticipate Catheter-Related Urinary Tract Contaminations in Seriously Care Units: Philosophy of Nursing
Authors: Rusmini Sri , Pandin Moses Glorino Rumambo 
Published: December 2023

ABSTRACTBackgroundUrinary tract infections are among the adverse outcomes of urinary catheter placement. After the installation of a catheter, urinary tract infections happen more often than twice a day. Examining prevention strategies for UTIs in critical care units is the aim of this writing audit.MethodUse ProQuest, Scopus, and ScienceDirect to look up review literature. Urinary tract infections, prevention and management, and intensive care unit were the search terms used to find publications. Search parameters for full-text, open-access, English-language papers published between 2019 and 2023.ResultsThe study’s findings indicate that adherence to patient information recording, installation and maintenance procedures, guidelines for the detection and prevention of CAUTI, staff education and good nursing practices, and the application of CAUTI prevention can all help lower the incidence of urinary tract infections.ConclusionHealthcare facilities need to have a program in place to avoid urinary tract infections brought on by catheter installation, as well as the best care possible for patients who use them. In order to solve the problem, all interdisciplinary teams must collaborate and analyze the issue using the PDSA methodology.
Leveraging neuroscience education to address stigma related to opioid use disorder (OUD) in the community: A pilot study
Authors: Kyzar Evan J. , Arbuckle Melissa , Abba-Aji Adam , Balachandra Krishna , Cooper Joseph , Dela Cruz Adriane , Edens Ellen , Heward Brady , Jibson Michael , Jordan Ayana , Moreno-De-Luca Daniel , Pazderka Hannah , Singh Mohit , Weleff Jeremy , Yau Bernice , Young Justin , Ross David A. 
Published: December 2023

AbstractOpioid use disorder (OUD) and overdose deaths are a public health crisis. One contributing factor is stigma towards people who use opioids. We developed and conducted a public-facing, half-day educational event designed to challenge misperceptions about OUD from a contemporary neuroscience perspective. Participants engaged with three different resources on the neurobiology of addiction; at the end of the event, they rated its effectiveness. We also collected and compared pre- and post-event composite OUD stigma scales. Participants rated our approach and the overall event as highly effective. Additionally, OUD stigma scores were lower immediately following the event, and this decrease was primarily driven by decreased internalized stigma. Here, we demonstrate an effective proof-of-concept that an accessible, public-facing, neuroscience education event may reduce OUD stigma in the community.
Bifurcation Coronary Intervention is Associated with Higher Mortality and Complications
Authors: Nathan Allistair , Hashemzadeh Mehrtash , Movahed Mohammad Reza 
Published: December 2023

AbstractBackgroundPercutaneous coronary intervention (PCI) in patients with bifurcation lesions is associated with higher complexity and adverse outcomes. The goal of this study was to evaluate the inpatient outcomes of patients with PCI of bifurcation lesions.MethodsThe National Inpatient Sample (NIS) database, years 2016-2020, was studied using ICD 10 codes. Patients with bifurcation lesion PCI were compared to other PCIs excluding chronic total occlusions (CTO). We evaluated post-procedural inpatient mortality and complications.ResultsPCI in patients with a bifurcation lesion was associated with higher mortality and post-procedural complications. A weighted total of 9,795,154 patients underwent PCI, with 43,480 having a bifurcation lesion. The bifurcation group had a 3.79% mortality rate vs 2.56%. (OR, 1.50; CI:1.34–1.68; p<0.001). After adjusting for age, sex, race, diabetes mellitus, and chronic kidney disease, bifurcation lesion PCI remained significantly associated with higher mortality (OR, 1.68; 95% CI, 1.49– 1.88; p<0.001). Furthermore, bifurcation PCI was associated with higher rates of myocardial infarction (OR, 2.26; 95% CI, 1.68 – 3.06; p<0.001), coronary perforation (OR, 7.97; 95% CI, 6.25-10.17; p<0.001), tamponade (OR, 3.46; 95% CI, 2.49-4.82, p<0.001), and procedural bleeding (OR, 5.71; 95% CI, 4.85-6.71, p<0.001). All post-procedural complications were more than 4 times more likely in patients with bifurcation than in those without (OR, 4.33; 95% CI, 3.83-4.88; p<0.001).ConclusionUsing a large national inpatient database, PCI performed in patients with a Non-CTO bifurcation lesions were associated with significantly higher mortality and post-procedural complications.
EEG-Based Frequency Domain Separation of Upward and Downward Movements of the Upper Limb
Authors: Ahangama T.V. , Gurunayake G.M.K.G.G.B. , Yalpathwala I.A. , Wijayakulasooriya J.V. , Dassanayake T.L. , Harischandra N. , Kim Kwangtaek , Ranaweera R.D.B. 
Published: December 2023

ABSTRACTOne of the fundamental challenges encountered when implementing the Motor Imagery based Brain-Computer Interfacing (BCI) paradigm is accurately classifying the Electroencephalography (EEG) signals that originate due to the same joint movements. This emanates from the limited spatial proximity in the corresponding brain regions. Here, we explore the feasibility of distinguishing arm-reaching movements specific to the right hand using multiple frequency bands in EEG signals despite the limited spatial differentiation of induced potentials. To address this challenge, a channel averaging method was used combining six electrodes positioned in close proximity to the motor cortex, intending to isolate and enhance electromagnetic activity in the brain associated with arm movements. This study was further refined by focusing on two distinct frequency bands: mu (8-12Hz) and beta (12-30Hz), each associated with different cognitive and motor functions. The results of our study revealed promising outcomes across two classification methods. Utilizing the Support Vector Machine (SVM) classification method, our proposed approach achieved an average accuracy of 59.3% while the K-Nearest Neighbors (KNN) classification approach yielded an average accuracy of 61.63% in distinguishing between upward and downward movements of the right arm.
Implementation of Agile in health care: Methodology for a multi-site home hospital accelerator
Authors: Desai Meghna , Tardif-Douglin Miriam , Miller Indigo R. D. , Blitzer Stephanie C. , Gardner David L. , Thompson Teresa M. , Edmondson LaPonda , Levine David M. 
Published: December 2023

AbstractBackgroundThe diffusion of innovation in health care is sluggish. Evidence-based care models and interventions take years to reach patients. We believe the health care community could deliver innovation to the bedside faster if it followed other sectors by employing an organizational framework for efficiently accomplishing work. Home hospital is an example of sluggish diffusion. This model provides hospital-level care in a patient’s home instead of in a traditional hospital with equal or better outcomes. Home hospital uptake has steadily grown during the COVID-19 pandemic, yet barriers to launch remain for health care organizations, including access to expertise and implementation tools. The Home Hospital Early Adopters Accelerator was created to bring together a network of health care organizations to develop tools necessary for program implementation.MethodsThe Accelerator used the Agile framework known as Scrum to rapidly coordinate work across many different specialized skill sets and blend individuals who had no experience with one another into efficient teams. Its goal was to take 40 weeks to develop 20 “knowledge products,” or tools critical to the development of a home hospital program such as workflows, inclusion criteria, and protocols. We conducted a mixed methods evaluation of the Accelerator’s implementation, measuring teams’ productivity and experience.ResultsEighteen health care organizations participated in the Accelerator to produce the expected 20 knowledge products in only 32 working weeks, a 20% reduction in time. Nearly all (97.4%) participants agreed or strongly agreed the Scrum teams worked well together, and 96.8% felt the teams produced a high-quality product. Participants consistently remarked that the Scrum team developed products much faster than their respective organizational teams. The Accelerator was not a panacea: it was challenging for some participants to become familiar with the Scrum framework and some participants struggled with balancing participation in the Accelerator with their job duties.ConclusionsImplementation of an agile-based accelerator that joined disparate health care organizations into teams equipped to create knowledge products for home hospital proved both efficient and effective. We demonstrate that implementing an organizational framework to accomplish work is a valuable approach that may be transformative for the sector.
A yeast modular cloning (MoClo) toolkit expansion for optimization of heterologous protein secretion and surface display inSaccharomyces cerevisiae
Authors: O’Riordan Nicola M. , Jurić Vanja , O’Neill Sarah K. , Roche Aoife P. , Young Paul W. 
Published: December 2023

ABSTRACTSaccharomyces cerevisiaeis an attractive host for expression of secreted proteins in a biotechnology context. Unfortunately, many heterologous proteins fail to enter, or efficiently progress through, the secretory pathway, resulting in poor yields. Similarly, yeast surface display has become a widely used technique in protein engineering but achieving sufficient levels of surface expression of recombinant proteins is often challenging. Signal peptides (SPs) and translational fusion partners (TFPs) can be used to direct heterologous proteins through the yeast secretory pathway, however, selection of the optimal secretion promoting sequence is largely a process of trial and error. The yeast modular cloning (MoClo) toolkit utilises Type IIS restriction enzymes to facilitate efficient assembly of expression vectors from standardized parts. We have expanded this toolkit to enable the efficient incorporation of a panel of sixteen well-characterized SPs and TFPs and five surface display anchor proteins intoS. cerevisiaeexpression cassettes. The secretion promoting signals were validated using five different proteins of interest. Comparison of intracellular and secreted protein levels revealed the optimal secretion promoting sequence for each individual protein. Large, protein of interest-specific variations in secretion efficiency were observed. SP sequences were also used with the five surface display anchors and the combination of SP and anchor protein proved critical for efficient surface display. These observations highlight the value of the described panel of MoClo compatible parts to allow facile screening of SPs, TFPs and anchor proteins for optimal secretion and/or surface display of a given protein of interest inS. cerevisiae.GRAPHICAL ABSTRACT
Rapid High-Throughput Method for Investigating Physiological Regulation of Neutrophil Extracellular Trap Formation
Authors: Zukas Kieran , Cayford Justin , Serneo Finley , Atteberry Brandi , Retter Andrew , Eccleston Mark , Kelly Theresa K 
Published: December 2023

Neutrophils, the most abundant white blood cells in humans, play pivotal roles in innate immunity, rapidly migrating to sites of infection and inflammation to phagocytose, neutralize, and eliminate invading pathogens. Neutrophil Extracellular Trap (NET) formation in response to pathogens is increasingly recognized as an essential rapid innate immune response, but when dysregulated contributes to pathogenesis of sepsis and immunothrombotic disease. Current models of NETosis are limited, routinely employing non-physiological triggers that can bypass natural NET regulatory pathways. Models utilizing isolated neutrophils and immortalized cell lines, do not reflect the complex biology underlying neutrophil activation and NETosis, that occurs in whole-blood. Here we describe a novel, high-throughputex-vivowhole blood induced NETosis model using combinatorial pooling of native NETosis inducing factors in a more biologically relevant Synthetic-Sepsis™ model. We found different combinations of factors evoked distinct neutrophil responses in the rate of NET generation and/or magnitude of NETosis. Despite inter-donor variability, similar sets of pro-inflammatory molecules induced consistent responses across donors. We found at least three biological triggers were necessary to induce NETosis in our system including either TNF-α or LT-α. To our knowledge, we report the first humanex-vivomodel utilizing naturally occurring molecules to induce NETosis in whole blood. This approach could be used for drug screening and, importantly, inadvertent activators of NETosis. These findings emphasize the importance of investigating neutrophil physiology in a biologically relevant context to enable a better understanding of disease pathology, risk factors, and therapeutic targets, potentially, providing novel strategies for disease intervention and treatment.EssentialsNETosis is a vital immune response, but dysregulation leads to disastrous health outcomes.Current NETosis models don’t reflect the complex endogenous signaling that occurs in whole bloodNetosis induction stimuli differs between isolated neutrophils and whole blood.A minimum of three physiological factors are required to induce NETosis in whole blood.
Clustered Regularly Interspaced Short Palindromic Repeats-Cas system regulatesSalmonellavirulence
Authors: Sharma Nandita , Das Ankita , Nair Abhilash Vijay , Sethi Palash , Negi Vidya Devi , Chakravortty Dipshikha , Marathe Sandhya Amol 
Published: December 2023

AbstractObjectivesInvestigating the type 1-E CRISPR-Cas-mediated regulation ofSalmonellapathogenesis.MethodsWe assessed the pathogenicity of the wild-type and CRISPR-Cas knockout strains using infection models. The mechanisms were elucidated using antimicrobial assays and expression analysis.ResultsCRISPR-Cas knockout strains were defective in invasion and proliferation in intestinal epithelial cells and macrophages. However, proliferation defects were not observed in the Gp91phox-/-macrophages, suggesting the system’s role in antioxidant defence. The knockout strains show hampered colonization inin-vivoinfection models, possibly due to increased sensitivity against innate immune barriers like antimicrobial peptides, complement proteins and oxidative stress. The expression studies of various virulence regulators:pmrgenes, anti-oxidant genes, SPI-1 and SPI-2 encoded master regulators, and effectors showed repressed expression in the knockout strains. Some of these genes could be directly regulated by the CRISPR-spacers owing to partial complementarity between the sequences.ConclusionOverall, our study shows that the CRISPR-Cas system positively regulatesSalmonellapathogenesis by regulating the expression of different virulence factors.
Inhibition of hERG K channels by verapamil at physiological temperature: Implications for the CiPA Initiative
Authors: Johnson Ashley A. , Trudeau Matthew C. 
Published: December 2023

AbstractThe Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative reassesses using the inhibition of hERG channels by drugs as the major determinant for assessment of a drug’s potential to cause ‘Torsades de Pointes’ (TdP) cardiac arrhythmias. Here we report on one phase of CiPA: independent determination of hERG inhibitory properties in order to test the reproducibility of data gathered in different labs and the practicality of using the CiPA-defined recording conditions. We measured inhibition of hERG1a potassium channels stably expressed in HEK293 cells using manual whole-cell patch-clamp electrophysiology recordings at the physiological temperature of 37°C by verapamil, a known hERG inhibitor. We report that the IC50 for inhibition (180.4nM) and the Hill coefficient (1.4) for verapamil measured in an academic lab were similar to the IC50 (204nM) and Hill coefficient (0.9) measured at the Food and Drug Administration labs, indicating low variability in measurements between labs. We report that the CiPA step voltage protocol, a series of voltage steps characterized by 10 second duration depolarizing pulses at 37°C, resulted in a very low (5%) experimental success rate per cell in our hands. To circumvent the low success rate, we shortened the duration of the depolarizing pulse to 3 seconds (from 10 seconds) and shortened the duration of interpulse intervals, which is more consistent with the duration of voltage pulses used in biophysical studies of hERG, such that the entire revised protocol was shortened from over 30 minutes to approximately 10 minutes in duration. Using the revised protocol, we found an IC50 of inhibition by verapamil of 210.5 nM and Hill coefficient of 1.2. These values were similar to those generated using the original, longer CiPA step protocol. Furthermore, our success rate using the shortened protocol rose to 25%, an increase of 5-fold over the initial protocol. In summary, we captured key pharmacological data for subsequent analysis in CiPA using a revised, shorter protocol with an enhanced success rate and an overall enhanced feasibility. We propose the shorter protocol is more pragmatic for generation of hERG channel drug inhibition data for CiPA and other regulatory sciences.