bluuebunny/crossref_metadata_2025 huggingface dataset:
The Future of Magnet®
Authors: Pappas Sharon , Lal M. Maureen
Published: September 2023

The Magnet Recognition Program® is built on the results of a study. Magnet® has continued to be evidence-based and forward reaching with each new manual requirement. The foundation of the Forces of Magnetism combined with current future-facing evidence continues to promote a culture of excellence. While it is nursing recognition, Magnet is an organizational credential from which an entire organization benefits.
The Disruption of Patient Ambulation Care Processes by COVID-19
Authors: Jones-Hooker Christa , Tyndall Deborah E. , Forbes Thompson H.
Published: September 2023

OBJECTIVE

To explore the impact of COVID-19 on care processes and ambulation outcomes.

BACKGROUND

COVID-19 forced hospital leaders to make systems-level changes that disrupted patient ambulation. The impact of these changes on the ambulation of hospitalized patients was unknown. The Systems Engineering Initiative for Patient Safety model was used to explore ambulation from a systems perspective.

METHODS

A single-case study research design was used to investigate patient ambulation in a major medical center. Data from 12 interviews with interdisciplinary leaders were analyzed.

RESULTS

Staff shortages and visitor restrictions were identified as the main work system barriers to ambulation. These barriers disrupted usual ambulation processes and supported the value of visitor assistance with ambulation.

CONCLUSIONS

This study provides a systems-level perspective of missed ambulation during COVID-19, which revealed the value of ambulation assistance provided by visitors. Findings may be used to support the continued and increased involvement of family members and visitors in the process of ambulation.
Leadership Styles and Nurses' Innovative Behaviors
Authors: Labrague Leodoro J. , Toquero Lei Marcelle
Published: September 2023

OBJECTIVE

In an increasingly competitive healthcare climate, ensuring an innovative nursing workforce is essential for organizational success and survival.

BACKGROUND

The authors aimed to evaluate the literature examining the association between leadership styles and innovative behaviors in the nursing workforce.

METHODS

A systematic review of articles from 5 databases was conducted from August 2022 to October 2022.

RESULTS

A total of 21 articles published in the English language were included in the review. This study provides evidence for the vital role of “relationship-oriented” leadership styles in fostering innovative behaviors among nurses. However, more research is needed to examine how “task-oriented” leadership styles contribute to innovativeness in nurses. Twelve mediators linking leadership styles to healthcare workers' innovative behaviors were identified and clustered into motivation-based, relation-based, and affective mediators.

CONCLUSION

Organizational strategies to foster relationship-based leadership styles among healthcare leaders are vital to support nurses' innovative behaviors.
The Utility of the Schnur Sliding Scale in Adolescent Patients
Authors: Donnenfield Jonah I. , Nuzzi Laura C. , McNamara Catherine T. , White Ava G. , Labow Brian I.
Published: September 2023

Background:

Although the Schnur Sliding Scale (SSS) was not intended to be used by third-party payors, it has become the national standard for coverage decisions regarding macromastia treatment in patients of all ages. Adolescents were neither included in the cohort that created the SSS nor represented in subsequent validation studies.

Methods:

In this prospective study, health-related quality of life surveys were administered to girls and young women 12 to 21 years of age before and after reduction mammaplasty to treat macromastia. The SSS was used preoperatively to estimate the amount of tissue to be resected. Before and after surgery, participants completed the Short Form–36, version 2 (SF-36); the Rosenberg Self-Esteem Scale (RSES); the Breast-Related Symptoms Questionnaire (BRSQ); and the Eating Attitudes Test–26. Demographic data were compared, and linear regressions were used to evaluate the effect of resection amounts meeting the SSS value on survey scores.

Results:

Resection amounts fell below the SSS for 39 patients and above the SSS for 255 patients. The 2 groups had no differences in mean age or body mass index. Both groups had significant postoperative survey score improvements on the RSES, BRSQ, and 7 of 8 SF-36 domains (all P < 0.05). The groups had comparable postoperative survey scores on the RSES, BRSQ, and 8 of 8 SF-36 domains (all P > 0.05).

Conclusions:

Adolescents undergoing reduction mammaplasty above and below the SSS experienced comparable physical and psychosocial benefits. These findings underscore the need for third-party payors to broaden coverage for adolescent reduction mammaplasty, as the common coverage cutoff has no effect on overall postoperative benefit.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, II.
Complications and Associated Risk Factors for Bimaxillary Osteotomies: A 15-Year Single-center Retrospective Study
Authors: Kotaniemi Karoliina V.M. , Suojanen Juho , Palotie Tuula
Published: September 2023

Aim:

The aim of this study was to retrospectively investigate the risk factors and their association on bimaxillary osteotomies to be able to improve patient selection and bimaxillary osteotomy planning.

Material and Methods:

Patients treated with a bimaxillary osteotomy were included in the study. The complications were collected retrospectively from the patient data records. The effects of certain predictor variables on complication rates were also studied.

Results:

Sixty-one patients (48.0%) suffered from peri- or postoperative complications, or both. Twenty-five various perioperative complications were reported on 25 patients (19.6%) and 63 postoperative complications on 46 patients (36.2%). Ten patients (7.8%) suffered from both perioperative and postoperative complications. The effect of various predictor variables (sex, age, general health, type of malocclusion, surgery planning, use of bone grafts, and type of maxillary or mandibular movement) on complications was investigated, but we could not find any single factor to affect significantly on complication rate.

Conclusion:

Both perioperative and postoperative complications are common in bimaxillary surgery, which must be noted in patient preoperative information. However, life-threatening complications are rare. Patient profile, bone grafting, type of osteosynthesis, or segmentation of the maxilla do not seem to affect the complication risk.
Realgar toxicity in terms of its chemical characterization, pharmacological mechanisms, and metabolic profile: A review
Authors: Yi Yan , Li Chunying , Zhao Yong , Liang Aihua
Published: September 2023

Realgar is an arsenic-containing Chinese medicine known for its toxin-removing, phlegm-dispelling, and malaria-intercepting effects. It has proven to be effective in the treatment of acute promyelocytic leukemia. However, because of the harmful nature of arsenic to human health, realgar is considered a “poison” in many countries, raising concerns about the toxicity and safety of realgar and its preparations. The Shuifei process (grinding with water) of realgar plays a crucial role in ensuring its safety as a Chinese medicine. The major ingredient of realgar, As4S4, is water insoluble and poorly absorbed by the human body. Therefore, it is important to note that the toxicity and health risks of realgar to humans are overestimated by solely considering the amount of arsenic. Realgar processing is an indispensable method to ensure the quality of medicinal realgar, involving purification, powdering, detoxification, and synergism. This article not only highlights possible mechanisms through which realgar exerts pharmacological effects but also reviews the literature regarding its toxic features and potential mechanisms. Currently, realgar toxicity research primarily relies on animal experiments, and clinical data on its adverse reactions are relatively limited. The toxicity of arsenic is closely related to the form and valence of its major metabolites in the body. Animal studies have confirmed that, when realgar enters the body, the major form of arsenic metabolized is dimethylarsenic acid; therefore, it was considered that the toxicity of realgar induced by high doses might be associated with the accumulation of dimethylarsenic acid produced in the methylation pathway of inorganic arsenic. Realgar is generally less toxic when used in safe doses, but prolonged use may pose a significant risk. It is rarely used alone and is often combined with other Chinese medicines in an attempt to reduce toxicity. Scientifically and reasonably limiting the arsenic content of realgar-containing Chinese patent medicines is an effective way to improve the safety of realgar in clinical medication.
Qingjin Huatan decoction attenuates lipopolysaccharide-induced acute lung injury in mice by controlling platelet-associated formation of neutrophil extracellular traps
Authors: Xiao Shunli , Wang Yilin , Liu Lu , Sun Zhengxiao , Xu Jing , Yin Xiaojie , Wang Xin , Liao Fulong , You Yun , Zhang Huamin
Published: September 2023

Background

Acute lung injury (ALI) is a severe and life-threatening lung inflammation with high morbidity and mortality, underscoring the importance to develop effective drugs. Qingjin Huatan decoction (QJHTD), as a classic ancient prescription, has been widely used for treating respiratory diseases. However, the role and mechanism of QJHTD against ALI remain unclear.

Objective

This study aimed to explore the therapeutic effect of QJHTD on lipopolysaccharide (LPS)-induced ALI in mice and uncover its mechanism.

Methods

The therapeutic effect of QJHTD on LPS-induced ALI in mice was evaluated by the histopathological changes in the lung tissue, the lung wet/dry weight ratio, and the levels of inflammatory cytokines and thrombin-antithrombin complexes. Transcriptomics was used to predict the mechanism of QJHTD in treating ALI. The expression levels of citrullinated histone 3 in the lung tissue, the content of cell-free DNA in the bronchoalveolar lavage fluid (BALF), and the platelet-associated formation of neutrophil extracellular traps (NETs) in vitro were determined.

Results

Qingjin Huatan decoction exerted protective effect against LPS-induced ALI by suppressing interstitial edema, maintaining the alveolar-capillary barrier, inhibiting the infiltration of neutrophils and platelets in the lung tissue, and lowering the levels of tumor necrosis factor α, interleukin 1β, interleukin 6, and thrombin-antithrombin complexes in BALF. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that the formation of NETs was the main regulatory pathway for QJHTD against ALI. Qingjin Huatan decoction could treat ALI by inhibiting the release of NETs via reducing the content of citrullinated histone 3 in lung tissue and cell-free DNA in BALF in vivo, and suppressing the NETs formation induced by LPS-stimulated platelets under flow and static conditions in vitro. The formation of NETs was considered to bridge the interactions between neutrophils and platelets.

Conclusions

This research demonstrated the effects of QJHTD in treating ALI and provided new insights for clarifying the complex regulation of neutrophils, platelets, and NETs in ALI.
Emerging trend of Vancomycin Resistant Enterococcal Bacteremia in a university hospital in Northern India – An observational analysis
Authors: Sarawat Deepika , Varghese Gerlin , Jamwal Ashima , Patel Sangram Singh , Tejan Nidhi , Sahu Chinmoy
Published: September 2023

Introduction: Vancomycin Resistant Enterococcus (VRE) species has been increasing and is now of serious concern. timely analysis of VRE bacteremia must be done in every institution to find the pattern of VRE prevalence.
Aim: To find the prevalence of VRE bacteremia at our institution. Also, the demographic pattern, associated risk factors, sensitivity pattern and outcomes associated with bacteremia caused by VRE were also estimated.
Methods: This observational study was done in the Microbiology department of our institute from April 2022 to June 2023. All patients with blood cultures positive for Enterococcus species for the first time during the study period were included in the study. The Blood culture bottles were loaded in the BACT/ALERT system. Once the bottle flagged a positive signal, culture was done and Gram staining was done. Identification was done using MALDI-Tof MS. Antimicrobial Sensitivity Testing was done by Kirby Bauer disk diffusion method and interpreted using Clinical and Laboratory Standards Institute (CLSI) 2023 M-100 clinical breakpoints. The demographic details, risk factors, and the clinical outcome of the patients included in the study were collected and analyzed.
Results: During the study period, 29086 blood culture bottles were received. Of these, 2016 (6.93%) bottles flagged positive. Enterococcus species were isolated from 256 (12.69%) blood cultures. Of the 256 Enterococcus isolates, 45 (17.57%) isolates were Vancomycin Resistant Enterococcus (VRE). The most common species isolated were Enterococcus faecium (n=42; 93.33%), followed by Enterococcus faecalis (n=2; 4.44%) and Enterococcus gallinarum (n=1; 2.22%). Most of the patients belonged to the age group 41-60 years (n=14; 31.11%). Male:Female ratio was 1.25:1. Diabetes mellitus and neutropenia were found to be significant risk factors among patients with VRE bacteremia. All the isolates showed 100% resistance to Teicoplanin, Ampicillin, Ampicillin-sulbactam and Levofloxacin. In 29 (64.44%) patients, bacteremia was the cause of death. On univariate analysis, mortality was found to be significantly higher in patients with Vancomycin Resistant Enterococcal (VRE) bacteremia as compared to patients with Vancomycin Sensitive Enterococcal (VSE) bacteremia.
Conclusion: An increasing prevalence of VRE bacteremia was observed in the study. Proper implementation of antimicrobial stewardship rules in the hospital is the best way to overcome the increasing trend of resistance.
Automated Deep Learning-Based Diagnosis and Molecular Characterization of Acute Myeloid Leukemia using Flow Cytometry
Authors: Lewis Joshua E. , Cooper Lee A.D. , Jaye David L. , Pozdnyakova Olga
Published: September 2023

Current flow cytometric analysis of blood and bone marrow samples for diagnosis of acute myeloid leukemia (AML) relies heavily on manual intervention in both the processing and analysis steps, introducing significant subjectivity into resulting diagnoses and necessitating highly trained personnel. Furthermore, concurrent molecular characterization via cytogenetics and targeted sequencing can take multiple days, delaying patient diagnosis and treatment. Attention-based multi-instance learning models (ABMILMs) are deep learning models which make accurate predictions and generate interpretable insights regarding the classification of a sample from individual events/cells; nonetheless, these models have yet to be applied to flow cytometry data. In this study, we developed a computational pipeline using ABMILMs for the automated diagnosis of AML cases based exclusively on flow cytometric data. Analysis of 1,820 flow cytometry samples shows that this pipeline provides accurate diagnoses of acute leukemia [AUROC 0.961] and accurately differentiates AMLversusB- and T- lymphoblastic leukemia [AUROC 0.965]. Models for prediction of 9 cytogenetic aberrancies and 32 pathogenic variants in AML provide accurate predictions, particularly for t(15;17)(PML::RARA) [AUROC 0.929], t(8;21)(RUNX1::RUNX1T1) [AUROC 0.814], andNPM1variants [AUROC 0.807]. Finally, we demonstrate how these models generate interpretable insights into which individual flow cytometric events and markers deliver optimal diagnostic utility, providing hematopathologists with a data visualization tool for improved data interpretation, as well as novel biological associations between flow cytometric marker expression and cytogenetic/molecular variants in AML. Our study is the first to illustrate the feasibility of using deep learning-based analysis of flow cytometric data for automated AML diagnosis and molecular characterization.
Dynamics of endogenous and water cortisol release in Asian SeabassLates calcariferafter acute stress in a farm scale recirculating aquaculture system
Authors: Tan Marie Ruoyun , Aung Khin Moh Moh , Salleh Nur Asinah binte Mohamed , Tan Jolin Yean Ai , Chua Kai Xin , Doblado Gaynah Javier , Chua Kai Lin , Tham Valarie , Lin Jovian Jing , Chaganty Vindhya , Yusoff Dinah Mardhiana , Vij Shubha , Su Xiaodi , Sutarlie Laura , Wee Caroline Lei
Published: September 2023

Stress in farmed fish is associated with poor feeding, slow growth, disease, and mortality. Therefore, it is essential to closely monitor the stress levels in fish to optimize farming practices which could then enhance productivity and welfare in aquaculture operations. Cortisol, a stress hormone that can be found in the blood, is a reliable biomarker for evaluating fish stress. As blood sampling is highly invasive, alternative cortisol sampling methods such as fin, mucus, and the surrounding water which contains released cortisol, have been proposed as less invasive or non-invasive sampling methods. However, a comprehensive understanding of their temporal dynamics and associations with plasma cortisol levels is still lacking. In this study, we subjectedLates calcarifer, Asian sea bass within a farm-scale (3,000 L tank, 9,000 L system) high-flow rate (8,000 L/hour) Recirculating Aquaculture System (RAS) to an acute handling stress challenge specifically involving chasing and air exposure, and quantified cortisol dynamics both within different biological samples including blood, fin, and mucus and in tank water from multiple sampling points. We showed that handling stress induced an expected increase in plasma and mucosal cortisol, peaking at 1 hour and 24-48 hours, respectively, and that plasma and mucus cortisol were moderately correlated, especially during the stress period. Fin cortisol did not show consistent dynamics. Water cortisol similarly rose, but peaked within 40 minutes from the start of the stressor, in a pattern that was dependent on the site of sampling within the RAS system, likely due to RAS circulation dynamics. Our study is the first to examine the impact of stress on cortisol accumulation and release in Asian Sea bass in a farm-scale RAS, thus complementing existing research on the efficacy of fin, mucus, and water cortisol as stress indicators that could help optimize aquaculture productivity and welfare.
Disparities of Female Authorship in Colombia: A 5-year Cross-sectional Analysis
Authors: Gutierrez-Torres Maria Alejandra , Ruiz Silvana , Morales Karen , Serpa Frans , Rincon Laura , Gómez Camila , Ahrens Michelle M. , Duran Felipe , Manzano Abul Ariza , Callegari Santiago
Published: September 2023

Accepted medical journal manuscripts serve as the primary currency of the scientific community. Over the past few decades, there has been a gradual increase in the number of women entering the medical field. However, women remain underrepresented as first and last authors in medical journals. This lack of representation makes it harder for them to reach leadership roles and advance in their academic careers. Therefore, this study aims to investigate the gender distribution among authors and explore disparities in authorship in relation to the type of publication (original research, case reports, and review articles) as well as the authors’ geographic locations. Our analysis included 6,088 articles from 54 research journals sourced from Colombia’s Ministry of Health official website. These articles were predominantly original research articles, although case reports and reviews were also present. The analysis specifically focused on published research articles, as they are extensively studied in existing literature. Until now, there has been no assessment of gender disparities in authorship within medical and surgical specialty journals in Colombia. We could evidence persistent gender disparity in primary authorship in Colombia, regardless of the timeframe, location, or field of study. This emphasizes the urgent need for enhanced support for female researchers and equitable resource allocation to rectify regional imbalances. Furthermore, our findings highlight the imperative need to address gender disparities in authorship in medical and surgical research articles in Colombia and other Latin American countries.
Sleep quality worsened in an evening chronotype compared to others: a year-long longitudinal cohort study with prolonged lockdowns and restriction relaxations in RECETOX MU university employees
Authors: Ráčková Lucie , Kuruczová Daniela , Štěpaníková Irena , Bienertová-Vašků Julie
Published: September 2023

Background

In 2020, people around the world were challenged by the outbreak of the COVID-19 pandemic. Countries responded with various restrictions, including lockdowns and stay-at-home orders, in an attempt to prevent the spread of the disease. Citizens were thus subjected to unprecedented uncertainty and stress. Prolonged exposure to such conditions may impact human health and well-being. One of the core aspects of proper physiological functioning is sleep. This prospective longitudinal study aims to investigate sleep quality and its relationship to chronotype over a year-long period from September 2020.

Methods and findings

Our year-long longitudinal prospective study focused on an employee cohort (N=54) at the Research Centre for Toxic Compounds in the Environment (RECETOX) of Masaryk University in the Czech Republic. During the first half of this period, three lockdowns with a cumulative duration of 100 days were imposed. During the second half of this period, the imposed restrictions were relaxed. Individuals were measured quarterly, i.e. at five time points. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI) while chronotype was established using the Reduced Morningness-Eveningness Questionnaire (rMEQ). We also used Perceived Stress Scale (PSS-14), Beck Depression Inventory (BDI-II), and General Anxiety Disorder-7 (GAD-7) to address potential confounders. The response rates of valid measurements across time points ranged from 87.04 % to 61.11 %. Our results show that sleep quality significantly worsened across the year for the evening chronotype but improved for the neutral and early chronotypes. Overall, over the year the incidence of poor sleep decreased by 16.13 % with 95% CI [-6.10%; 37.16%]. We did not find any significant sex differences in sleep quality. Perceived stress, symptoms of anxiety and depression were positively significantly associated with sleep problems in all measurements except in June. This study is limited by the small sample, decreasing number of individuals in chronotype categories and the lack of information on napping behavior.

Conclusion

These findings shed new light on the long-term influence of pandemic-related restrictions on individuals and particularly on the potentially more vulnerable evening chronotypes.
Characterizing Low-cost Registration for Photographic Images to Computed Tomography
Authors: Kim Michael E. , Lee Ho Hin , Ramadass Karthik , Gao Chenyu , Van Schaik Katherine , Tkaczyk Eric , Spraggins Jeffrey , Moyer Daniel C. , Landman Bennett A.
Published: September 2023

Mapping information from photographic images to volumetric medical imaging scans is essential for linking spaces with physical environments, such as in image-guided surgery. Current methods of accurate photographic image to computed tomography (CT) image mapping can be computationally intensive and/or require specialized hardware. For general purpose 3-D mapping of bulk specimens in histological processing, a cost-effective solution is necessary. Here, we compare the integration of a commercial 3-D camera and cell phone imaging with a surface registration pipeline. Using surgical implants and chuck-eye steak as phantom tests, we obtain 3-D CT reconstruction and sets of photographic images from two sources: Canfield Imaging’s H1 camera and an iPhone 14 Pro. We perform surface reconstruction from the photographic images using commercial tools and open-source code for Neural Radiance Fields (NeRF) respectively. We complete surface registration of the reconstructed surfaces with the iterative closest point (ICP) method. Manually placed landmarks were identified at three locations on each of the surfaces. Registration of the Canfield surfaces for three objects yields landmark distance errors of 1.747, 3.932, and 1.692 mm, while registration of the respective iPhone camera surfaces yields errors of 1.222, 2.061, and 5.155 mm. Photographic imaging of an organ sample prior to tissue sectioning provides a low-cost alternative to establish correspondence between histological samples and 3-D anatomical samples.
A redox-shifted fibroblast subpopulation emerges in the fibrotic lung
Authors: Link Patrick A. , Meridew Jeffrey A. , Caporarello Nunzia , Gao Ashley Y. , Peters Victor , Smith Gordon B. , Rojas Mauricio , Tschumperlin Daniel J.
Published: September 2023

Idiopathic pulmonary fibrosis (IPF) is an aggressive and thus far incurable disease, characterized by aberrant fibroblast-mediated extracellular matrix deposition. Our understanding of the disease etiology is incomplete; however, there is consensus that a reduction-oxidation (redox) imbalance plays a role. In this study we use the autofluorescent properties of two redox molecules, NAD(P)H and FAD, to quantify changes in their relative abundance in living lung tissue of mice with experimental lung fibrosis, and in freshly isolated cells from mouse lungs and humans with IPF. Our results identify cell population-specific intracellular redox changes in the lungs in experimental and human fibrosis. We focus particularly on redox changes within collagen producing cells, where we identified a bimodal distribution of NAD(P)H concentrations, establishing NAD(P)Hhighand NAD(P)Hlowsub-populations. NAD(P)Hhighfibroblasts exhibited elevated pro-fibrotic gene expression and decreased collagenolytic protease activity relative to NAD(P)Hlowfibroblasts. The NAD(P)Hhighpopulation was present in healthy lungs but expanded with time after bleomycin injury suggesting a potential role in fibrosis progression. We identified a similar increased abundance of NAD(P)Hhighcells in freshly dissociated lungs of subjects with IPF relative to controls, and similar reductions in collagenolytic activity in this cell population. These data highlight the complexity of redox state changes in experimental and human pulmonary fibrosis and the need for selective approaches to restore redox imbalances in the fibrotic lung.
Moving Biosurveillance Beyond Coded Data: AI for Symptom Detection from Physician Notes
Authors: McMurry Andrew , Zipursky Amy R , Geva Alon , Olson Karen L , Jones James , Ignatov Vlad , Miller Timothy , Mandl Kenneth D
Published: September 2023

Background

Real-time surveillance of emerging infectious diseases necessitates a dynamically evolving, computable case definition, which frequently incorporates symptom-related criteria. For symptom detection, both population health monitoring platforms and research initiatives primarily depend on structured data extracted from electronic health records.

Objective

To validate and test an artificial intelligence (AI) based Natural Language Processing (NLP) pipeline for detecting COVID-19 symptoms from physician notes.

Methods

Subjects in this retrospective cohort study are patients 21 years old and younger, who presented to a pediatric emergency department (ED) at a large academic children’s hospital between March 1, 2020 and May 31, 2022. ED notes for all patients were processed with an NLP pipeline tuned to detect the mention of 11 COVID-19 symptoms based on CDC criteria. For a gold standard, 3 subject matter experts labeled 226 ED notes and had strong agreement (F1=98.6; PPV=97.2; Recall=100.0). F1, PPV, and recall were used to compare the performance of both NLP and ICD-10 to the gold standard chart review. As a formative use case, variations in symptom patterns were measured across SARS-Cov2 variant eras.

Results

There were 85,678 ED encounters during the study period, 4.0% with patients with COVID-19. NLP was more accurate at identifying encounters with patients that had any of the COVID-19 symptoms (F1=79.6) than ICD-10 codes (F1=45.1%). NLP accuracy was higher for positive symptoms (recall=93%) than ICD-10 (recall=30%). However, ICD-10 accuracy was higher for negative symptoms (specificity=99.4%) than NLP (specificity=91.7%). Congestion or runny nose showed the highest accuracy difference: NLP F1=82.8%, ICD-10 F1=4.2%. Prevalence of NLP symptoms among patients with COVID-19 differed across variant eras. And patients with COVID-19 were more likely to have each symptom than patients without this disease. Effect sizes (odds ratios) varied across pandemic eras.

Conclusions

This study establishes the value of AI based NLP as a highly effective tool for real-time COVID-19 symptom detection in pediatric patients, outperforming traditional ICD-10 methods. It also reveals the evolving nature of symptom prevalence across different virus variants, underscoring the need for dynamic, technology-driven approaches in infectious disease surveillance.
Automated Annotation of Disease Subtypes
Authors: Ofer Dan , Linial Michal
Published: September 2023

Background

Distinguishing diseases into distinct subtypes is crucial for study and effective treatment strategies. The Open Targets Platform (OT) integrates biomedical, genetic, and biochemical datasets to empower disease ontologies, classifications, and potential gene targets. Nevertheless, many disease annotations are incomplete, requiring laborious expert medical input. This challenge is especially pronounced for rare and orphan diseases, where resources are scarce.

Methods

We present a machine learning approach to identifying diseases with potential subtypes, using the approximately 23,000 diseases documented in OT. We derive novel features for predicting diseases with subtypes using direct evidence. Machine learning models were applied to analyze feature importance and evaluate predictive performance for discovering both known and novel disease subtypes.

Results

Our model achieves a high (89.4%) ROC AUC (Area Under the Receiver Operating Characteristic Curve) in identifying known disease subtypes. We integrated pre-trained deep-learning language models and showed their benefits. Moreover, we identify 515 disease candidates predicted to possess previously unannotated subtypes.

Conclusions

Our models can partition diseases into distinct subtypes. This methodology enables a robust, scalable approach for improving knowledge-based annotations and a comprehensive assessment of disease ontology tiers. Our candidates are attractive targets for further study and personalized medicine, potentially aiding in the unveiling of new therapeutic indications for sought-after targets.
Cost-Benefit Analysis for Universal Cataract Coverage in India
Authors: Arora Anoushka , Vuddemarry Madhurima , Reddy Chaitanya , Iyer Himanshu , Nimkar Pushkar , Zadey Siddhesh
Published: September 2023

Purpose

To calculate the annual enhanced coverage costs for covering the total and unmet need of cataract in India. To calculate the economic benefits of cataract burden averted. To calculate the net benefits of covering cataract needs.

Setting

We look at population-level data of India and its 30 states.

Design

This is a retrospective cross-sectional analysis for 2018-19.

Methods

We conducted a retrospective cross-sectional analysis for India and its 30 states. Data was taken from Global Burden of Disease 2019, the National Health Profile 2020, and the National Health Accounts 2021. We used ten per-capita surgical costs to calculate enhanced coverage costs. Enhanced coverage costs for the total need were calculated by multiplying prevalence with per-capita costs. For unmet need, the difference between the prevalence and surgeries achieved was used. For economic benefits of averted cataract burden, we multiplied disability-adjusted life-years (DALYs) with non-health GDP per capita, i.e., GDP - the government health expenditure. DALYs for unmet needs were calculated by multiplying DALYs with the ratio of unmet to total needs. For net benefits, we subtracted the enhanced coverage costs for meeting total and unmet needs from economic benefits.

Results

The annual enhanced coverage costs for covering total cataract needs in India were 0.92 - 4.9 billion USD. Costs for covering unmet needs were 0.72 - 3.82 billion USD. Nationally, the economic benefit of averting the total cataract disease burden was 12.4 (95%UI: 8.9 - 16.7) billion USD, while the for covering the unmet burden was 9.7 (95%UI: 6.93 - 13) billion USD. Annual net benefits of covering total needs were 7.53 - 11.5 billion USD. Net benefits of covering unmet needs were 5.9 - 9 billion USD.

Conclusion

Enhancing coverage for cataract is cost-beneficial.
Longitudinal associations between mild behavioral impairment, sleep disturbance, and progression to dementia
Authors: Mudalige Dinithi , Guan Dylan X. , Ghahremani Maryam , Ismail Zahinoor
Published: September 2023

Background

Clinical guidelines recommend incorporating non-cognitive markers like mild behavioral impairment (MBI) and sleep disturbance (SD) into dementia screening to improve detection.

Objective

We investigated the longitudinal associations between MBI, SD, and incident dementia.

Methods

Participant data were from the National Alzheimer’s Coordinating Center in the United States. MBI was derived from the Neuropsychiatric Inventory Questionnaire (NPI-Q) using a published algorithm. SD was determined using the NPI-Q nighttime behaviors item. Cox proportional hazard regressions with time-dependant variables for MBI, SD, and cognitive diagnosis were used to model associations between baseline 1) MBI and incident SD (n=11277); 2) SD and incident MBI (n=10535); 3) MBI with concurrent SD and incident dementia (n=13544); and 4) MBI without concurrent SD and incident dementia (n=11921). Models were adjusted for first-visit age, sex, education, cognitive diagnosis, race, and for multiple comparisons using the Benjamini-Hochberg method.

Results

The rate of developing SD was 3.1-fold higher in older adults with MBI at baseline compared to those without MBI (95%CI: 2.8-3.3). The rate of developing MBI was 1.5-fold higher in older adults with baseline SD than those without SD (95%CI: 1.3-1.8). The rate of developing dementia was 2.2-fold greater in older adults with both MBI and SD, as opposed to SD alone (95%CI:1.9-2.6).

Conclusions

There is a bidirectional relationship between MBI and SD. Older adults with SD develop dementia at higher rates when co-occurring with MBI. Future studies should explore the mechanisms underlying these relationships, and dementia screening may be improved by assessing for both MBI and SD.
Work-Related Musculoskeletal Disorders among Nurses Working at Hospitals of Sudurpaschim Province, Nepal
Authors: Bhatta Deepa Kumari , Bhandari Gajananda Prakash , Duwadi Nirmal , Bhatta Bal Krishna , Gurung Ishwori , Dahal Alisha
Published: September 2023

Musculoskeletal conditions have been ranked as the leading cause of disability worldwide. Low back pain is the single largest contributor in 160 countries including Nepal. Nurses working in hospitals in Nepal are overworked and at risk of developing musculoskeletal disorders. The study aimed to determine the 12-month periods and point prevalence of work-related musculoskeletal disorders (WMSDs); the predictors, and the perceived risk factors among nurses. A self-administered standard Nordic questionnaire was distributed among all eligible 118 nurses working at two hospitals. Bivariate and multivariate logistic regression analyses were applied to identify the predictors of WMSDs. Study findings revealed that nearly half (47.46%) of nurses had WMSDs most significantly affecting the lower back (18.93%). Nurses exceeding 30 years of age had almost seven times higher odds of having WMSDs compared to their counterparts aged less than 30 adjusting the effects of BMI, department, years of clinical experience, and type of hospital (OR= 6.92; CI =1.67-28.58). There was decreased odds of experiencing WMSDs by 0.33 times for nurses working in a private hospital than in a government hospital adjusting the effect of age, BMI, department, and years of clinical experience (OR=0.33; 95% CI=0.12-0.91). Similarly, nurses working in critical units had 5.24 times higher odds of having musculoskeletal disorders than in general units (OR=5.25; 95% CI=1.79-15.38). Nurses working for more than five years had 7.53 times higher odds of having WMSDs than those with less than and equal to five years of work experience (OR=7.53; CI 2.78-20.32). WMSDs are common among nurses primarily affecting the lower back and the odds of having MSDs is high with increasing age, BMI, and work experience, and for nurses who worked in critical care units and public hospital. Prompt preventive measures should be adopted to avoid risk factors of MSDs in work settings.Keywords:Works related to musculoskeletal disorders, nursing, prevention, perceived risk factors
Association between kidney measurements and cognitive performance in patients with ischemic stroke
Authors: Zhang Chunyan , Xue Guofang , Hou Yanjuan , Meng Pengfei , Gao Huizhong , Bai Bo , Li Dongfang
Published: September 2023

Background

Relationships between low estimated glomerular filtration rate (eGFR) and albuminuria with poorer cognitive performance in patients with ischemic stroke are less clear. Our aim was to retrospectively ascertain the associations between these renal measures and cognitive performance in patients with ischemic stroke.

Methods

Retrospective analysis was performed on 608 patients with acute ischemic stroke. Urine albumin-creatinine ratio (UACR) and eGFR were obtained from inpatient medical records. Global cognitive function via mini-mental state exam (MMSE) and Montreal Cognitive Assessment (MoCA) was determined one month after hospital discharge. The relationship between renal measures and cognitive performance was assessed using univariate and multiple linear regression analyses.

Results

Patients had an average age of 66.6±4.1 years, and 48% were females. Average eGFR and UACR were 88.4±12.9 ml/min/1.73m2and 83.6±314.2 mg/g, respectively. The number of patients with an eGFR of ≥90, 60 to 89, and <60 ml/min/1.73 m2were (371, 61%), (207, 34%) and (30, 5%) respectively. The proportions with a UACR <30 mg/g, 30-300mg/g and >300 mg/g were 56%, 39% and 5%. Multivariate adjusted models showed that eGFR was independently associated with MMSE (β= –0.4; 95% CI= –0.5,-0.4; p <0.001) and MoCA (β = –0.6; 95% CI= –0.7,-0.5; p <0.001). However, the correlations between UACR and MMSE and MoCA were statistically non-significant.

Conclusion

In patients with ischemic stroke, reduced eGFR but not albuminuria was associated with lower cognitive performance. These results show that the eGFR decline could be an effective indicator of cognitive impairment after a stroke. Therefore, regular monitoring and early detection of mild renal dysfunction in patients with acute ischemic stroke might be needed.
Autophagic cargo in Lewy bodies: are Lewy bodies a compartment for spatial protein quality control?
Authors: Conod Phoebe , Charlesworth Nicola , Palmowski Pawel , Porter Andrew , Walker Lauren , El-Agnaf Omar , Korolchuk Viktor , Outeiro Tiago F. , Erskine Daniel
Published: September 2023

Lewy bodies are neuropathologically associated with Lewy body dementia (LBD), but little is known about why they form or their role in the disease process. We previously reported Lewy bodies are a common feature of older individuals with primary mitochondrial diseases. However, as they are not an invariant finding, understanding differences between those with and without Lewy bodies may provide insights into factors that govern the formation of Lewy bodies in Lewy body disease (LBD). The present study sought to investigate whether deficient mitophagy in the context of mitochondrial dysfunction may underlie Lewy body formation.Post-mortemtissue was obtained from the cingulate gyrus and dorsal motor nucleus of the vagal nerve (DMV) of mitochondrial disease cases with Lewy bodies, primary mitochondrial disease cases without Lewy bodies, and control cases, in addition to LBD cases as comparison. An array of mitophagy and autophagy markers were quantified in 50 individual neurons per cingulate gyrus and all neurons per DMV using immunofluorescent analysis. No significant differences were found between groups, although there was a striking enrichment of markers of autophagic mitochondria and autophagic vesicles within Lewy bodies. Evaluation of diffuse α-synuclein aggregates, thought to precede Lewy body formation, suggested only autophagic mitochondria were present in early aggregates, perhaps suggesting sequestration of dysfunctional mitochondria is an early step in Lewy body formation. To characterise the composition of Lewy bodies, discovery proteomics was performed on isolated insoluble proteins from frozen cingulate gyrus, which identified up-regulation of markers of aggresomes, a regulated cellular response that occurs when protein degradative pathways become overwhelmed, a mechanism of spatial protein quality control (sPQC). Taken together, these findings are consistent with impairment of cellular waste handling pathways in Lewy body-bearing neurons, and that the formation of a Lewy body could be a deliberate cellular response to compartmentalise such waste.
Dynamic subtype- and context-specific subcellular RNA regulation in growth cones of developing neurons of the cerebral cortex
Authors: Veeraraghavan Priya , Engmann Anne K. , Hatch John J. , Itoh Yasuhiro , Nguyen Duane , Addison Thomas , Macklis Jeffrey D.
Published: September 2023

Molecular mechanisms that cells employ to compartmentalize function via localization of function-specific RNA and translation are only partially elucidated. We investigate long-range projection neurons of the cerebral cortex as highly polarized exemplars to elucidate dynamic regulation of RNA localization, stability, and translation within growth cones (GCs), leading tips of growing axons. Comparison of GC-localized transcriptomes between two distinct subtypes of projection neurons– interhemispheric-callosal and corticothalamic– across developmental stages identifies both distinct and shared subcellular machinery, and intriguingly highlights enrichment of genes associated with neurodevelopmental and neuropsychiatric disorders. Developmental context-specific components of GC-localized transcriptomes identify known and novel potential regulators of distinct phases of circuit formation: long-distance growth, target area innervation, and synapse formation. Further, we investigate mechanisms by which transcripts are enriched and dynamically regulated in GCs, and identify GC-enriched motifs in 3 ’ untranslated regions. As one example, we identifycytoplasmic adenylation element binding protein 4(CPEB4), an RNA binding protein regulating localization and translation of mRNAs encoding molecular machinery important for axonal branching and complexity. We also identifyRNA binding motif single stranded interacting protein 1(RBMS1) as a dynamically expressed regulator of RNA stabilization that enables successful callosal circuit formation. Subtly aberrant associative and integrative cortical circuitry can profoundly affect cortical function, often causing neurodevelopmental and neuropsychiatric disorders. Elucidation of context-specific subcellular RNA regulation for GC- and soma-localized molecular controls over precise circuit development, maintenance, and function offers generalizable insights for other polarized cells, and might contribute substantially to understanding neurodevelopmental and behavioral-cognitive disorders and toward targeted therapeutics.
A conserved role of hnRNPL in regulating alternative splicing of transcriptional regulators necessary for B cell activation
Authors: Subramani Poorani Ganesh , Fraszczak Jennifer , Helness Anne , Estall Jennifer L. , Möröy Tarik , Noia Javier M Di
Published: September 2023

The multifunctional RNA-binding protein hnRNPL has been implicated in antibody class switching but its broader function in B cells is unknown. Here, we show that hnRNPL is essential for B cell activation, and thereby germinal center and antibody responses. Upon activation, hnRNPL-deficient B cells show proliferation defects and increased apoptosis. Comparative analysis of RNA-seq data from activated B cells and another 8 hnRNPL-depleted cell types reveals a common function in the MYC and E2F transcriptional programs required for proliferation, likely borne out of alternative splicing changes affecting multiple transcription regulators. Notably, while individual gene expression changes were cell type specific, several alternative splicing events affecting histone modifiers like, KDM6A, NSD2, and SIRT1, were conserved across cell types, which could contribute to gene expression changes and other phenotypes upon hnRNPL loss. In line with reduced SIRT1, hnRNPL-deficient B cells had dysfunctional mitochondria and ROS overproduction, which could contribute to defects in B cell activation. Thus, hnRNPL is essential for the resting-to-activated B cell transition by regulating transcriptional programs and metabolism, most likely through the alternative splicing of several histone modifiers.
The effects of queen mandibular pheromone on nurse-aged honey bee (Apis mellifera) hypopharyngeal gland size and lipid metabolism
Authors: Oreshkova Angela , Scofield Sebastian , Amdam Gro V.
Published: September 2023

Queen honey bees (Apis mellifera) release Queen Mandibular Pheromone (QMP) to regulate traits in the caste of female helpers called workers. QMP signals the queen’s presence and suppresses worker reproduction. In the absence of reproduction, young workers take care of the queen and her larvae (nurse tasks), while older workers forage. In nurses, QMP increases lipid stores in abdominal fat tissue (fat body) and protein content in hypopharyngeal glands (HPG). HPG are worker-specific head glands that can synthesize royal jelly used in colony nourishment. Larger HPG signifies ability to secrete royal jelly, while shrunken glands characterize foragers that do not make jelly. While it is known that QMP increases abdominal lipid stores, the mechanism is unclear: Does QMP make workers consume more pollen which provides lipids, or does QMP increase lipogenic capacity? Here, we measure abdominal lipogenic capacity as fatty acid synthase (FAS) activity while monitoring abdominal protein content and HPG size in caged workers. Cages allow us to rigorously control worker age, pheromone exposure, and diet. In our 2-factorial design, 3-vs. 8-day-old workers (age factor) were exposed to synthetic QMP or not (pheromone factor) while consuming a lipid deficient diet. We found that QMP did not influence abdominal FAS activity or protein content, but QMP still increased HPG size in the absence of dietary lipids. Our data revealed a positive correlation between abdominal protein content and HPG size. Our findings show that QMP is not a strong modulator of lipogenic capacity in caged worker bees. However, our data may reflect that QMP mobilizes abdominal protein for production of jelly, in line with previous findings on effects of honey bee Brood Pheromone. Overall, our study expands the understanding of how QMP can affect honey bee workers. Such insights are important beyond regulatory biology, as QMP is used in various aspects of beekeeping.