bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Development and Implementation of a Preconception Counseling Program for Black Women and Men in the Southeastern United States: A Pilot Protocol
Authors: Hernandez-Green N. , Haiman M. , McDonald A. , Rollins L. , Franklin C.G. , Farinu O.T.O , Clarke L. , Huebshmann A. , Fort M. , Chandler R. , Brocke P. , McLaurin-Glass D. , Harris E. , Berry K. , Suarez A. , Williams T. 
Published: April 2024

AbstractIntroductionRacial/ethnic disparities in maternal mortality rates represent one of the most significant areas of disparities amongst all conventional population perinatal health measures in the U.S. The alarming trends and persistent disparities of outcomes by race/ethnicity and geographic location reinforce the need to focus on ensuring quality and safety of maternity care for all women. Despite complex multilevel factors impacting maternal mortality and morbidity, there are evidence-based interventions that, when facilitated consistently and properly, are known to improve the health of mothers before, during and after pregnancy. The objective of this project is to test implementation of pre-conception counseling with father involvement in community-based settings to improve cardiovascular health outcomes before and during pregnancy in southeastern United States.Methods and AnalysisThis study has two components: a comprehensive needs and assets assessment and a small-scale pilot study. We will conduct a community informed needs and assets assessment with our diverse stakeholders to identify opportunities and barriers to preconception counseling as well as develop a stakeholder-informed implementation plan. Next, we will use the implementation plan to pilot preconception counseling with father involvement in community-based settings. Finally, we will critically assess the context, identify potential barriers and facilitators, and iteratively adapt the way preconception counseling can be implemented in diverse settings. Results of this research will support future research focused on identifying barriers and opportunities for scalable and sustainable public health approaches to implementing evidence-based strategies that reduce maternal morbidity and mortality in the southeastern United States’ vulnerable communities.DiscussionFindings will demonstrate that preconception counseling can be implemented in community health settings in the southeastern United States. Furthermore, this study will build the capacity of community-based organizations in addressing the preconception health of their clients. We plan for this pilot to inform a larger scaled-up clinical trial across community health settings in multiple southeastern states.
EZH2: A Critical Competing Endogenous RNA in Cancer Research - A Scoping Review
Authors: Salehi-Mazandarani Sadra , Mahmoudian-Hamedani Sharareh , Farajzadegan Ziba , Nikpour Parvaneh 
Published: April 2024

AbstractIn recent years, research on the competing endogenous RNAs (ceRNAs) in cancer is in full swing. These investigations are discovering the importance of critical RNAs in cancer progression. Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) is one of these RNAs that has been identified as a potential therapeutic target in many types of cancer. Up to now, many studies have been conducted to elucidate ceRNA role ofEZH2in cancer. Due to EZH2’s dual role as an oncogene and tumor suppressor in cancer, a more thorough exploration of its ceRNA functions may enhance clinical approaches to cancer treatment. In the current scoping review, we searched online databases including PubMed, Web of Science, Scopus, Embase, Cochrane Library, and Google Scholar to identify experimentally-validated ceRNA axes includingEZH2in human cancers. We identified 62 unique axes consisting of 30 microRNAs (miRNAs), 31 long non-coding RNAs (lncRNAs), 9 messenger RNAs (mRNAs), and 14 circular RNAs (circRNAs). Notably,SPRY4-IT1- miR-101-3p -EZH2andXIST- miR-101-3p -EZH2were recurrent axes observed in multiple cancer types. Among the most frequent miRNAs were miR-101-3p, miR-144-3p, and miR-124-3p, and ceRNAs includingSPRY4-IT1,XIST,SNHG6,HOXA11-AS,MALAT1, andTUG1emerged as frequent competitors ofEZH2for miRNA binding. This scoping review highlights the prevalence and diversity ofEZH2-containing ceRNA axes in cancer, suggesting their potential as therapeutic targets. Future research should delve deeper into these axes to elucidate their functional significance and assess their clinical applicability.
Evaluation ofin silico toolsfor variant classification in missense variants of solid cancer with actionable genetic targets
Authors: Hong Ilene , Yu Emma , Song Chiwoo , Kim Eugene , Lee Grace , Lee Alice , Chae Young Kwang 
Published: April 2024

AbstractAdvancement in next-generation sequencing technologies has led to a rise in discovery of variants of uncertain significance, which are not clearly categorized as pathogenic or benign. In silico tools, which have been developed to help classify these variants, exhibit variations in outcome. This study aims to evaluate the performance of 6 widely-used in silico tools in predicting the pathogenicity of drug-actionable gene variants in 9 solid cancers.We selected drug-actionable genes according to NCCN guidelines on breast, ovarian, colorectal, melanoma of skin, thyroid, bladder, pancreatic, prostate, and biliary cancer. From these genes, we gathered information on 1161 total missense variants (pathogenic = 606, benign = 555). Each variant’s pathogenicity was determined based on assertions from three databases: ClinVar, OncoKB, and My Cancer Genome. We selected variants with one or more concordant databases and excluded variants with conflicting classifications. The performance of the in silico tools (Align-GVGD, CADD, FATHMM, MutationTaster2021, Polyphen-2 (HumDiv), and Polyphen-2 (HumVar)) was evaluated by calculating and comparing their overall accuracy, sensitivity, specificity, and Matthews correlation coefficient (MCC).Overall, all of the in silico tools demonstrated high sensitivity (0.738-0.927) and moderately-high accuracy (0.555-0.829). Excluding MutationTaster2021, all tools demonstrated low specificity (0.242-0.559) and MCC (0.107-0.413). MutationTaster2021 exhibited the highest performance overall and across solid cancer types. Conversely, Align-GVGD exhibited low performance overall and across cancer types.Tools demonstrating high sensitivity (CADD: 0.983, MutationTaster2021: 0.927, REVEL: 0.851) could be used to rule out the pathogenic variants. MutationTaster2021, with a comparatively high specificity (0.721), could be considered as an additional test to rule in the pathogenic variants. However, given the varying performance and limitations of the tools according to solid cancer type, clinicians should remain cautious in their usage.
Optimizing Input Selection for Cardiac Model Training and Inference: An Efficient 3D CNN-based Approach to Automate Coronary Angiogram Video Selection
Authors: Chang Shih-Sheng , Rostami Behrouz , LoRusso Gerardo , Liu Chia-Ha , Alkhouli Mohamad 
Published: April 2024

AbstractBackgroundResearch leveraging deep learning (DL) for medical image analysis is increasingly using dynamic coronary angiography from cardiac catheterizations to train neural networks. Yet, an efficient, automatic method to select appropriate dynamic images for training is still largely missing.MethodsWe developed DL models using 254 coronary angiographic studies from the Mayo Clinic. We utilized two state-of-the-art Convolutional Neural Networks (CNN: ResNet and X3D), to identify low quality angiograms through binary classification (satisfactory/unsatisfactory). Ground truth for the quality of the input angiogram was determined by two experienced cardiologists. We validated the developed model in an independent dataset of 3,208 procedures from 3 Mayo sites.Results3D-CNN models outperformed their 2D counterparts, with the X3D model achieving superior performance across all metrics (AUC 0.98, precision 0.86, and sensitivity 0.89). The 2D models processed the video clips faster than 3D models. Despite having a 3D architecture, the X3D model had lower computational demand (2.56 GMAC) and parameter count (2.98 M) than 2D models. When validating models on the independent dataset, slight decreases in AUC and sensitivity were observed but accuracy and specificity remained robust (0.88 and 0.89, respectively for the X3D model).ConclusionWe developed a rapid and effective method for automating the selection of coronary angiogram video clips using 3D-CNNs, potentially improving model accuracy and efficiency in clinical applications. The X3D-S model demonstrates a balanced trade-off between computational efficiency and complexity, making it suitable for real-life clinical applications.
The Association of Racial Residential Segregation and Survival After Out-of-Hospital Cardiac Arrest in the United States
Authors: Abbott Ethan E , Buckler David G , Shekhar Aditya C , Landry Elizabeth , Abella Benjamin S , Richardson Lynne D , Zebrowski Alexis M ,   CARES Surveillance Group
Published: April 2024

AbstractBackgroundResidential segregation has been identified as drivers of disparities in health outcomes, but further work is needed to understand this association with clinical outcomes for out-of-hospital cardiac arrest (OHCA). We utilized Cardiac Arrest Registry to Enhance Survival (CARES) dataset to examine if there are differences in survival to discharge and survival with good neurological outcome, as well as likelihood of bystander CPR, using validated measures of racial, ethnic, and economic segregation.MethodsWe conducted a retrospective observational study using data from the Cardiac Arrest Registry to Enhance Survival (CARES) dataset to examine associations among adult OHCA patients. The primary predictor was the Index of Concentration at the Extremes (ICE), a validated measure that includes race, ethnicity, and income across three measures at the census tract level. The primary outcomes were survival to discharge and survival with good neurological status. A multivariable modified Poisson regression modeling approach with random effects at the EMS agency and hospital level was utilized.ResultsWe identified 626,264 OHCA patients during the study period. The mean age was 62 years old (SD 17.2 years), and 35.7% (n =223,839) of the patients were female. In multivariable models, we observed an increased likelihood of survival to discharge and survival with good neurological outcome for those patients residing in predominately White population census tracts and higher income census tracts as compared to lower income Black and Hispanic/Latinx population census tracts (RR 1.24, CI 1.20-1.28) and a 32% increased likelihood of receiving bystander CPR in higher income census tracts as compared to reference (RR 1.32, CI 1.30-1.34).ConclusionsIn this study examining the association of measures of residential segregation and OHCA outcomes, there was an increased likelihood of survival to discharge, survival with good neurological status, and likelihood of receiving B-CPR for those patients residing in predominately White population and higher income census tracts when compared to predominately Black and/or Hispanic Latinx populations and lower income census tracts. This research suggests that areas impacted by residential and economic segregation are important targets for both public policy interventions as well as addressing disparities in care across the chain of survival for OHCA.
Analysis of Hypertension in Peru: Prevalence, Associated Factors, Knowledge, Management and Control, 2014-2022
Authors: Vera-Ponce Víctor Juan , Zuzunaga-Montoya Fiorella E. , Vásquez-Romero Luisa Erika Milagros , Loayza-Castro Joan A. , Iturregui Paucar Cori Raquel , Valladares-Garrido Mario J. , Vigil-Ventura Enrique 
Published: April 2024

AbstractIntroductionHypertension (HTN), prehypertension, and High Blood Pressure (HBP) represent a chronic medical condition of growing global concern. Highlighting the importance of Awareness, medication, and Control of HTN is essential. A significant proportion of hypertensive patients are unaware of their condition, hindering proper and early treatment. Among those diagnosed, not all receive or follow pharmacological treatment, and an even smaller percentage achieves effective blood pressure control.ObjectiveThe main objectives include determining the prevalence, trends, and associated factors of HTN, as well as investigating prehypertension and the variability in HBP levels during the same period. Special attention will be given to self-reported, medicated, and Controlled hypertension, analyzing its evolution and associated factors.MethodsWe conducted an analytical cross-sectional study using the National Survey of Demographic and Family Health database between 2014 and 2022. Our study included individuals aged 18 years and older, as the definitions of HTN apply to people from this age onwards.ResultsThe study revealed an overall HTN, prehypertension, and HBP prevalence of 20.76%, 33.44%, and 33.44%, respectively, with annual variations. An increasing trend in the prevalence of known, medicated, and controlled HTN was observed, with factors such as gender, age, educational level, and geographical region significantly influencing it.ConclusionsThe investigation into HTN in Peru revealed an expanding occurrence of HTN, prehypertension, and HBP, emphasizing the necessity for early identification, suitable treatment, and effective management of HTN. A significant gap is observed between the condition’s awareness and effective management, highlighting the urgent need for public health strategies that address both the prevention and treatment of HTN in Peru.
Insights into Predicting Tooth Extraction from Panoramic Dental Images: Artificial Intelligence vs. Dentists
Authors: Motmaen Ila , Xie Kunpeng , Schönbrunn Leon , Berens Jeff , Grunert Kim , Plum Anna Maria , Raufeisen Johannes , Ferreira André , Hermans Alexander , Egger Jan , Hölzle Frank , Truhn Daniel , Puladi Behrus 
Published: April 2024

AbstractObjectivesTooth extraction is one of the most frequently performed medical procedures. The indication is based on the combination of clinical and radiological examination and individual patient parameters and should be made with great care. However, determining whether a tooth should be extracted is not always a straightforward decision. Moreover, visual and cognitive pitfalls in the analysis of radiographs may lead to incorrect decisions. Artificial intelligence (AI) could be used as a decision support tool to provide a score of tooth extractability.Material and MethodsUsing 26,956 single teeth images from 1,184 panoramic radiographs (PANs), we trained a ResNet50 network to classify teeth as either extraction-worthy or preservable. For this purpose, teeth were cropped with different margins from PANs and annotated. The usefulness of the AI-based classification as well that of dentists was evaluated on a test dataset. In addition, the explainability of the best AI model was visualized via a class activation mapping using CAMERAS.ResultsThe ROC-AUC for the best AI model to discriminate teeth worthy of preservation was 0.901 with 2% margin on dental images. In contrast, the average ROC-AUC for dentists was only 0.797. With a 19.1% tooth extractions prevalence, the AI model’s PR-AUC was 0.749, while the human evaluation only reached 0.589.ConclusionAI models outperform dentists/specialists in predicting tooth extraction based solely on X-ray images, while the AI performance improves with increasing contextual information.Clinical RelevanceAI could help monitor at-risk teeth and reduce errors in indications for extractions.
Association of aortic clamping time with systemic immune inflammation and systemic inflammatory response indexes in isolated coronary bypass surgery
Authors: Durmaz Duygu , Gündöner Sedat , Tekümit Hayrettin 
Published: April 2024

ObjectiveAortic clamping time during cardiopulmonary bypass (CPB) has been associated with inflammatory processes such as systemic inflammatory response syndrome. In this study, we evaluated the association of CPB and aortic cross-clamping (ACC) times with systemic inflammatory response index (SIRI) and systemic immune inflammation index (SIII) in isolated coronary artery bypass surgery (CABG).Methods96 patients who underwent isolated CABG at a single center between 2021 and 2023 were retrospectively analyzed. Patients were divided into below median aortic clamp time (group I; n=56) and above median aortic clamp time (group II; n=42) according to median aortic clamp time (66.2 minutes). Demographic data, preoperative and postoperative laboratory parameters were recorded. SIRI and SIII values were calculated.ResultsBaseline demographic data were similar between the groups. The duration of CPB and aortic clamping was significantly longer in group II (p<0.001). SIII and SIRI values were significantly increased in both groups in the postoperative period. However, there was no correlation between increased CPB and ACC durations and SIII and SIRI. However, no significant difference was observed in postoperative SIII and SIRI values between the groups. A weak correlation was found between SIII index and postoperative albumin levels.ConclusionsThere is no significant relationship between aortic clamping time and inflammatory indices in patients undergoing isolated CABG surgery. Increasing the duration of surgery does not affect the change in SIRI and SIII values.
Blood Pressure Control and Maintenance in a Prospective Cohort of Younger Veterans: Roles of Sex, Race, Ethnicity, and Social Determinants of Health
Authors: Gaffey Allison E. , Chang Tiffany E. , Brandt Cynthia A. , Haskell Sally G. , Dhruva Sanket S. , Bastian Lori A. , Levine Allison , Melissa Skanderson , Burg Matthew M. 
Published: April 2024

AbstractBackgroundProactive blood pressure (BP) management is particularly beneficial for younger Veterans, who have a greater prevalence and earlier onset of cardiovascular disease than non-Veterans. It is unknown what proportion of younger Veterans achieve and maintain BP control after hypertension onset and if BP control differs by demographics and social deprivation.MethodsElectronic health records were merged from Veterans who enrolled in VA care 10/1/2001-9/30/2017 and met criteria for hypertension – first diagnosis or antihypertensive fill. BP control (140/90 mmHg), was estimated 1, 2, and 5 years post-hypertension documentation, and characterized by sex, race, and ethnicity. Adjusted logistic regressions assessed likelihood of BP control by these demographics and with the Social Deprivation Index (SDI).ResultsOverall, 17% patients met criteria for hypertension (n=198,367; 11% of women, median age 41). One year later, 59% of men and 65% of women achieved BP control. After adjustment, women had a 72% greater odds of BP control than men, with minimal change over 5 years. Black adults had a 22% lower odds of BP control than White adults. SDI did not significantly change these results.ConclusionsIn the largest study of hypertension in younger Veterans, 41% of men and 35% of women did not have BP control after 1 year, and BP control was consistently better for women through 5 years. Thus, the first year of hypertension management portends future, long-term BP control. As social deprivation did not affect BP control, the VA system may protect against disadvantages observed in the general U.S. population.
Facile detection of peptide-protein interactions using an electrophoretic crosslinking shift assay
Authors: Parker Benjamin W. , Weiss Eric L. 
Published: April 2024

ABSTRACTProtein-protein interactions with high specificity and low affinity are functionally important but are not comprehensively understood because they are difficult to identify. Particularly intriguing are the dynamic and specific interactions between folded protein domains and short unstructured peptides known as short linear motifs (SLiMs). Such domain-motif interactions (DMIs) are often difficult to identify and study because affinities are modest to weak. Here we describe “electrophoretic crosslinking shift assay” (ECSA), a simple in vitro approach that detects transient, low affinity interactions by covalently crosslinking a prey protein and a fluorescently labeled bait. We demonstrate this technique on the well characterized DMI between MAP kinases and unstructured D-motif peptide ligands. We show that ECSA detects sequence-specific micromolar interactions using less than a microgram of input prey protein per reaction, making it ideal for verifying candidate low-affinity DMIs of components that purify with low yield. We propose ECSA as an intermediate step in SLiM characterization that bridges the gap between high throughput techniques such as phage display and more resource-intensive biophysical and structural analysis.
Natural compound screening predicts novel GSK-3 isoform-specific inhibitors
Authors: Ahmad Firdos , Gupta Anamika , Marzook Hezlin , Woodgett James R. , Saleh Mohamed A. , Qaisar Rizwan 
Published: April 2024

AbstractGlycogen synthase kinase-3 (GSK-3) plays important roles in the pathogenesis of cardiovascular, metabolic, neurological disorders and cancer. Isoform-specific loss of either GSK-3α or GSK-3β often provides cytoprotective effects under such clinical conditions. However, available synthetic small molecule inhibitors are relatively non-specific, and their chronic use may lead to adverse effects. Therefore, screening for natural compound inhibitors to identify the isoform-specific inhibitors may provide improved clinical utility. Here, we screened 70 natural compounds to identify novel natural GSK-3 inhibitors employing comprehensivein silicoand biochemical approaches. Molecular docking and pharmacokinetics analysis identified two natural compounds Psoralidin and Rosmarinic acid as potential GSK-3 inhibitors. Specifically, Psoralidin and Rosmarinic acid exhibited the highest binding affinities for GSK-3α and GSK-3β, respectively. Consistent within silicofindings, the kinase assay-driven IC50 revealed superior inhibitory effects of Psoralidin against GSK-3α (IC50=2.26 µM) vs. GSK-3β (IC50=4.23 µM) while Rosmarinic acid was found to be more potent against GSK-3β (IC50=2.24 µM) than GSK-3α (IC50=5.14 µM). Taken together, these studies show that the identified natural compounds may serve as GSK-3 inhibitors with Psoralidin serving as a better inhibitor for GSK-3α and Rosmarinic for GSK-3β isoform, respectively. Further characterization employingin vitroand preclinical models will be required to test the utility of these compounds as GSK-3 inhibitors for cardiometabolic and neurological disorders and cancers.HighlightsCurrent GSK-3 inhibitors lack specificity and cause side effects.This study identifies potential GSK-3 isoform-specific natural compounds.Psoralidin is likely a better inhibitor for GSK-3α while Rosmarinic for GSK-3β.These natural compounds may be promising future treatments.
Identification of a non-canonical function of prefoldin subunit 5 in proteasome assembly
Authors: Shahmoradi Ghahe Somayeh , Drabikowski Krzysztof , Topf Ulrike 
Published: April 2024

AbstractThe prefoldin complex is a heterohexameric, evolutionarily conserved co-chaperone that assists in the folding of polypeptides downstream of the protein translation machinery. Loss of prefoldin function leads to impaired solubility of cellular proteins. The degradation of proteins by the proteasome is an integral part of protein homeostasis. Failure of regulated protein degradation can lead to the accumulation of misfolded and defective proteins. We show that prefoldin subunit 5 is required for proteasome activity by contributing to the assembly of the 26S proteasome. In particular, we found that the absence of prefoldin subunit 5 impairs the formation of the Rpt ring subcomplex of the proteasome. Concomitant deletion ofPFD5andHSM3, a chaperone for assembly of the ATPase subunits comprising the Rpt ring, exacerbates this effect, suggesting a synergistic relationship between the two factors in proteasome assembly. Thus, our findings reveal a regulatory mechanism wherein prefoldin subunit 5 plays a crucial role in maintaining proteasome integrity, thereby influencing the degradation of proteins.