bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mdka produced by the activated HSCs drives bipotential progenitor cell redifferentiation during zebrafish biliary-mediated liver regeneration
Authors: Zhang Xintao , Liu Huijuan , Cai Pengcheng , Huang Zhuofu , Ma Jianlong , Luo Lingfei 
Published: July 2024

Background and Aims:
After extensive hepatocyte loss or impaired hepatocyte proliferation, liver regeneration occurs through trans-differentiation of biliary epithelial cells (BECs), which involves dedifferentiation of biliary epithelial cells into bipotential progenitor cells (BP-PCs) and subsequent redifferentiation of BP-PCs into nascent hepatocytes and biliary epithelial cells. Despite several studies on the redifferentiation process of BP-PCs into nascent hepatocytes, the contributions of nonparenchymal cells in this process remain poorly understood.

Approach and Results:
Using the zebrafish severe liver injury model, we observed specific expression of midkine a (Mdka) in the activated HSCs through single-cell analyses and fluorescence in situ hybridization. Genetic mutation, pharmacological inhibition, whole-mount in situ hybridizations, and antibody staining demonstrated an essential role of mdka in the redifferentiation of BP-PCs during liver regeneration. Notably, we identified Nucleolin (Ncl), the potential receptor for Mdka, specifically expressed in BP-PCs, and its mutant recapitulated the mdka mutant phenotypes with impaired BP-PC redifferentiation. Mechanistically, the Mdka-Ncl axis drove Erk1 activation in BP-PCs during liver regeneration. Furthermore, overexpression of activated Erk1 partially rescued the defective liver regeneration in the mdka mutant.

Conclusions:
The activated HSCs produce Mdka to drive the redifferentiation process of BP-PCs through activating Erk1 during the biliary-mediated liver regeneration, implying previously unappreciated contributions of nonparenchymal cells to this regeneration process.
Diagnostic Performance of Machine Learning-based Models in Neonatal Sepsis: A Systematic Review
Authors: Kainth Deepika , Prakash Satya , Sankar M. Jeeva 
Published: July 2024

Background:
Timely diagnosis of neonatal sepsis is challenging. We aimed to systematically evaluate the diagnostic performance of sophisticated machine learning (ML) techniques for the prediction of neonatal sepsis.

Methods:
We searched MEDLINE, Embase, Web of Science and Cochrane CENTRAL databases using “neonate,” “sepsis” and “machine learning” as search terms. We included studies that developed or validated an ML algorithm to predict neonatal sepsis. Those incorporating automated vital-sign data were excluded. Among 5008 records, 74 full-text articles were screened. Two reviewers extracted information as per the CHARMS (CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies) checklist. We followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guideline extension for diagnostic test accuracy reviews and used the PROBAST tool for risk of bias assessment. Primary outcome was a predictive performance of ML models in terms of sensitivity, specificity and positive and negative predictive values. We generated a hierarchical summary receiver operating characteristics curve for pooled analysis.

Results:
Of 19 studies (15,984 participants) with 76 ML models, the random forest algorithm was the most employed. The candidate predictors per model ranged from 5 to 93; most included birth weight and gestation. None performed external validation. The risk of bias was high (18 studies). For the prediction of any sepsis (14 studies), pooled sensitivity was 0.87 (95% credible interval: 0.75–0.94) and specificity was 0.89 (95% credible interval: 0.77–0.95). Pooled area under the receiver operating characteristics curve was 0.94 (95% credible interval: 0.92–0.96). All studies, except one, used data from high- or upper-middle-income countries. With unavailable probability thresholds, the performance could not be assessed with sufficient precision.

Conclusions:
ML techniques have good diagnostic accuracy for neonatal sepsis. The need for the development of context-specific models from high-burden countries is highlighted.
HIV Drug Resistance in Newly Diagnosed Young Children in the Western Cape, South Africa
Authors: Anderson Kim , van Zyl Gert , Hsiao Nei-Yuan , Claassen Mathilda , Mudaly Vanessa , Voget Jacqueline , Heekes Alexa , Kalk Emma , Phelanyane Florence , Boulle Andrew , Sridhar Gayathri , Ragone Leigh , Vannappagari Vani , Davies Mary-Ann 
Published: July 2024

Background:
Pretreatment of HIV drug resistance among children living with HIV (CLHIV) can compromise antiretroviral therapy (ART) effectiveness. Resistance may be transmitted directly from mothers or acquired following exposure to antiretrovirals consumed through breastfeeding or administered as prophylaxis.

Methods:
We performed resistance testing in children aged <3 years, newly diagnosed with HIV in Western Cape, South Africa (2021–2022), who either (1) acquired HIV via possible breastfeeding transmission from mothers who received ART (any regimen) during pregnancy/postpartum and/or (2) were exposed to protease inhibitors or integrase strand transfer inhibitors (INSTIs) in utero. Possible breastfeeding transmission was defined as testing HIV-polymerase chain reaction positive at age >28 days, after previously testing negative. We used surveillance drug–resistance mutation lists to define mutations.

Results:
We included 135 CLHIV. Most mothers started ART prepregnancy (73%). Overall, 57% (77/135) of children had resistance mutations detected. Nonnucleoside reverse transcriptase inhibitor–associated, nucleoside reverse transcriptase inhibitor–associated, protease inhibitor–associated and INSTI-associated mutations were found in 55% (74/135), 10% (13/135), <1% (1/135) and <1% (1/122) of children tested, respectively. One child with breastfeeding transmission had high-level INSTI resistance detected at HIV diagnosis, aged 18 months (E138K and G118R mutations).

Conclusions:
Although not clinically relevant, nonnucleoside reverse transcriptase inhibitor–associated mutations were common. Dolutegravir is currently the preferred first-line treatment for adults and CLHIV age ≥4 weeks, and although very low INSTI resistance levels have been observed in adults, limited data exist on genotyping the integrase region in children. Pretreatment INSTI resistance in children is likely to be unusual, but future surveillance, including longitudinal studies with paired mother-child resistance testing, is needed.
The Practical Management of Rhinitis in Athletes
Authors: Khalid Hesham , Tait Joanna E. , North Alexander S. , Lakhani Raj 
Published: July 2024

Objective:
Exercise-induced rhinitis (EIR) is a poorly understood condition that can have a massive impact within elite sport. This was epitomized in 2019 when British cyclist and Tour de France winner Chris Froome lost control of his bike at 37 mph while wiping his nose, resulting in an admission to intensive care. We aim to produce a comprehensive resource to guide the assessment and management of rhinitis in athletes.

Design:
Rhinitis is a common condition which can be broadly divided into allergic rhinitis (AR) and non-AR (NAR), a subset of which is known as vasomotor rhinitis. Exercise-induced rhinitis is an important but understudied subcategory of NAR. The pathophysiology of the disease is broadly believed to be an imbalance of the sympathetic and parasympathetic nervous systems, leading to symptoms of watery rhinorrhea, nasal congestion, and paroxysmal sneezing. Up to 50% of people suffer from some degree of EIR, which impedes their nasal breathing and affects performance. The assessment of the athlete with rhinitis requires consideration of both allergic and vasomotor contributions to ensure optimal management is introduced. There is no clear guidance for the management of EIR, with uncertainty regarding the most effective pharmaceuticals and optimizing the timing of treatment to enable peak performance.

Setting:
N/A.

Patients/Participants:
N/A.

Interventions:
N/A.

Main Outcome Measures:
N/A.

Results and Conclusions:
Based on expert clinical experience in a busy ear, nose, and throat center and a systematic review of current literature, this article proposes a step-wise, incremental approach to the management of EIR symptoms. In an industry where marginal gains give athletes a competitive edge, optimal management of EIR is crucial.
Exam Wrappers in Nursing Education
Authors: Gay Jessica E. , Kuskie Kathryn , Loken Alisha , Klenke-Borgmann Laura 
Published: July 2024

Background:
Metacognition can assist students in improving poor examination (exam) performance. An exam wrapper is a metacognitive tool used to assess a student’s thought processes and behavioral patterns during test-taking.

Purpose:
The purpose of this study was to determine the effect of an exam wrapper tool used during one-to-one exam review sessions with faculty on prelicensure nursing students’ subsequent exam performance.

Methods:
Paired t-tests and repeated measures ANOVA were used to compare undergraduate students’ (n = 91) exam scores before and after an exam review session with faculty in which the exam wrapper tool was used.

Results:
Students who completed a one-to-one exam review session with faculty using the exam wrapper showed significant improvement in subsequent exam scores.

Conclusions:
Use of an exam wrapper tool as part of a one-to-one exam review session with faculty is a viable way to leverage metacognition to improve student exam performance.
The Nature of Adverse Events in Dentistry
Authors: Tokede Bunmi , Yansane Alfa , Walji Muhammad , Rindal D. Brad , Worley Donald , White Joel , Kalenderian Elsbeth 
Published: July 2024

Objectives
Learning from clinical data on the subject of safety with regards to patient care in dentistry is still largely in its infancy. Current evidence does not provide epidemiological estimates on adverse events (AEs) associated with dental care. The goal of the dental practice study was to quantify and describe the nature and severity of harm experienced in association with dental care, and to assess for disparities in the prevalence of AEs.

Methods
Through a multistaged sampling procedure, we conducted in-depth retrospective review of patients’ dental and medical records.

Results
We discovered an AE proportion of 1.4% (95% CI, 1.1% to 1.8). At least two-thirds of the detected AEs were preventable. Eight percent of patients who experienced harm due to a dental treatment presented only to their physician and not to the dentist where they originally received care.

Conclusions
Although most studies of AEs have focused on hospital settings, our results show that they also occur in ambulatory care settings. Extrapolating our data, annually, at least 3.3 million Americans experience harm in relation to outpatient dental care, of which over 2 million may be associated with an error.

Practical Implications
Measurement is foundational in enabling learning and improvement. A critical first step in preventing errors and iatrogenic harm in dentistry is to understand how often these safety incidents occur, what type of incidents occur, and what the consequences are in terms of patient suffering, and cost to the healthcare system.
La Crosse virus encephalitis in children
Authors: Ouellette Christopher P. 
Published: July 2024

Purpose of review
La Crosse virus encephalitis (LACV-E) is among the most common neuroinvasive arthropod-borne viral infections of childhood in North America. Children are uniquely predisposed to symptomatic disease, whereas symptomatic adult infections remain uncommon. Infection results frequently in neurologic symptomatology including headaches, seizures, and altered mentation, often necessitating hospitalization and significant diagnostic evaluation. The purpose of this review is to provide a contemporary assessment of clinical, laboratory, and neurobehavioral outcomes of children with LACV-E.

Recent findings
Common clinical manifestations at presentation, specifically seizure activity and altered mental status, are independent predictors of disease severity. Epileptiform discharges on electroencephalogram (EEG) during hospitalization may predict long-term epilepsy diagnosis. Lastly, long-term neurologic sequelae from acute infection is persistent and likely under-recognized among children with LACV-E.

Summary
As climate change alters the geographic distribution of mosquito borne illnesses, a possibility of regional expansion of La Crosse virus (LACV) endemicity exists. The above data highlight readily identifiable features and testing modalities for clinicians who may encounter this viral infection. Importantly, an emphasis on long term neurobehavioral follow up is necessary to better identify and provide support of affected individuals. Future research in identifying host immune responses to LACV infection, as well as therapeutic options, are needed.
Racial Disparities in Nocturia Persist Regardless of BMI Among American Women
Authors: Napoe Gnankang Sarah , Kermah Dulcie , Mitchell Nia S. , Norris Keith 
Published: July 2024

Importance
It is crucial to understand the racial and ethnic disparities that exist in nocturia prevalence to appropriately manage nocturia.

Objectives
Nocturia is associated with increased body mass index (BMI) and is most prevalent in Black and Hispanic women, who also have the highest and second highest prevalence of obesity, respectively. We sought to better understand the association of nocturia with BMI category by race and ethnicity in U.S. women.

Study Design
This was a cross-sectional study using publicly available data from the National Health and Nutrition Examination Survey data from 2005 to 2018. We estimated the prevalence of moderate to severe nocturia (defined as 2 or more episodes of nighttime urination) by BMI category within each racial and ethnic (Black, White, Hispanic, and other) group of adult women. Logistic regression was performed to determine the odds ratio of nocturia by race.

Results
The odds of nocturia was 2.25 (2.04–2.49) for Black women, 1.27 (1.15–1.4) for Hispanic women and 0.96 (0.82–1.13) for other women compared to White women. After accounting for BMI, socioeconomic status and comorbidities, the adjusted odds ratio was 1.76 (1.42–2.16) for Black women, 1.1 (.0.88–1.38) for Hispanic women, and 0.81 (0.5–1.29) for other women compared to White women.

Conclusions
Black women were nearly twice as likely to have nocturia than White women. The increased odds of nocturia, while not sustained for Hispanic women, persisted for Black women regardless of socioeconomic status, BMI, and comorbidities. Our study suggests that there are factors other than weight driving the prevalence of nocturia in Black women that require further investigation.
Reemergence of Oropouche virus between 2023 and 2024 in Brazil
Authors: Scachetti Gabriel C. , Forato Julia , Claro Ingra M. , Hua Xinyi , Salgado Bárbara B. , Vieira Aline , Simeoni Camila L. , Barbosa Aguyda R. C. , Rosa Italo L. , de Souza Gabriela F. , Fernandes Luana C. N. , de Sena Ana Carla H. , Oliveira Stephanne C. , Singh Carolina M. L. , de Lima Shirlene T. , de Jesus Ronaldo , Costa Mariana A. , Kato Rodrigo B. , Rocha Josilene F. , Santos Leandro C. , Rodrigues Janete T. , Cunha Marielton P. , Sabino Ester C. , Faria Nuno R. , Weaver Scott C. , Romano Camila M. , Lalwani Pritesh , Proença-Módena José Luiz , de Souza William M. 
Published: July 2024

AbstractBackgroundOropouche virus (OROV; speciesOrthobunyavirus oropoucheense) is an arthropod-borne virus that has caused outbreaks of Oropouche fever in Central and South America since the 1950s. This study investigates virological factors contributing to the reemergence of Oropouche fever in Brazil between 2023 and 2024.MethodsIn this study, we combined OROV genomic, molecular, and serological data from Brazil from 1 January 2015 to 29 June 2024, along within vitroandin vivocharacterization. Molecular screening data included 93 patients with febrile illness between January 2023 and February 2024 from the Amazonas State. Genomic data comprised two genomic OROV sequences from patients. Serological data were obtained from neutralizing antibody tests comparing the prototype OROV strain BeAn 19991 and the 2024 epidemic strain. Epidemiological data included aggregated cases reported to the Brazilian Ministry of Health from 1 January 2014 to 29 June 2024.FindingsIn 2024, autochthonous OROV infections were detected in previously non-endemic areas across all five Brazilian regions. Cases were reported in 19 of 27 federal units, with 83.2% (6,895 of 8,284) of infections in Northern Brazil and a nearly 200-fold increase in incidence compared to reported cases over the last decade. We detected OROV RNA in 10.8% (10 of 93) of patients with febrile illness between December 2023 and May 2024 in Amazonas. We demonstrate that the 2023-2024 epidemic was caused by a novel OROV reassortant that replicated approximately 100-fold higher titers in mammalian cells compared to the prototype strain. The 2023-2024 OROV reassortant displayed plaques earlier than the prototype, produced 1.7 times more plaques, and plaque sizes were 2.5 larger compared to the prototype. Furthermore, serum collected in 2016 from previously OROV-infected individuals showed at least a 32-fold reduction in neutralizing capacity against the reassortment strain compared to the prototype.InterpretationThese findings provide a comprehensive assessment of Oropouche fever in Brazil and contribute to a better understanding of the 2023-2024 OROV reemergence. The recent increased incidence may be related to a higher replication efficiency of a new reassortant virus that also evades previous immunity.
Comprehensive Analysis of Atypical chronic myeloid leukemia (aCML): Epidemiology, Clinical Features, and Survival Outcomes Based on SEER Database Insights
Authors: Wang Fan 
Published: July 2024

AbstractBackgroundAtypical Chronic Myeloid Leukemia (aCML) is a rare and aggressive myelodysplastic syndrome/myeloproliferative neoplasm. This study aimed to provide a comprehensive understanding of the epidemiology, clinical characteristics, and survival outcomes of aCML patients.MethodsThe study utilized data from the Surveillance, Epidemiology, and End Results (SEER) database from 2001 to 2020. The age-adjusted incidence rate (AIR) of aCML was calculated, and survival outcomes were analyzed using the Kaplan-Meier method and accelerated failure time (AFT) regression analysis.ResultsThe AIR of aCML was found to be 0.024 per 100,000 person-years, with the highest rate observed in 2020. The incidence of aCML increased with age and was higher in males. The study cohort predominantly consisted of elderly White individuals, with an average age at diagnosis of 68.2 ± 15.3 years. The median overall survival (OS) and disease-specific survival (DSS) were 1.4 years and 1.7 years, respectively. Older age was independently associated with worse survival outcomes. Notably, treatment delay and chemotherapy did not significantly impact OS or DSS.ConclusionsThis study provides comprehensive insights into the epidemiology, clinical characteristics, and survival outcomes of aCML, highlighting its rarity, aggressive nature, and poor prognosis. Further research is needed to validate these findings and explore novel therapeutic strategies for improving outcomes in this challenging hematologic malignancy.
Towards Personalized Breast Cancer Risk Management: A Thai Cohort Study on Polygenic Risk Scores
Authors: Nakhonsri Vorthunju , Pithukpakorn Manop , Eu-ahsunthornwattana Jakris , Ngamphiw Chumpol , Wasitthankasem Rujipat , Wilantho Alisa , Wangkumhang Pongsakorn , Boonbangyang Manon , Tongsima Sissades 
Published: July 2024

AbstractPolygenic Risk Scores (PRS) are now playing an important role in predicting overall risk of breast cancer risk by means of adding contribution factors across independent genetic variants influencing the disease. However, PRS models may work better in some ethnic populations compared to others, thus requiring populaion-specific validation. This study evaluates the performance of 140 previously published PRS models in a Thai population, an underrepresented ethnic group. To rigorously evaluate the performance of 140 breast PRS models, we employed generalized linear models (GLM) combined with a robust evaluation strategy, including Five-fold cross validation and bootstrap analysis in which each model was tested across 1,000 bootstrap iterations to ensure the robustness of our findings and to identify models with consistently strong predictive ability. Among the 140 models evaluated, 38 demonstrated robust predictive ability, identified through > 163 bootstrap iterations (95% CI: 163.88). PGS004688 exhibited the highest performance, achieving an AUROC of 0.5930 (95% CI: 0.5903–0.5957) and a McFadden’s pseudo R2of 0.0146 (95% CI: 0.0139–0.0153). Women in the 90thpercentile of PRS had a 1.83-fold increased risk of breast cancer compared to those within the 30thto 70thpercentiles (95% CI: 1.04–3.18). This study highlights the importance of local validation for PRS models derived from diverse populations, demonstrating their potential for personalized breast cancer risk assessment. Model PGS004688, with its robust performance and significant risk stratification, warrants further investigation for clinical implementation in breast cancer screening and prevention strategies. Our findings emphasize the need for adapting and utilizing PRS in diverse populations to provide more accessible public health solutions.
Detection ofHepatovirus A(HAV) in wastewater indicates widespread national distribution and association with socioeconomic indicators of vulnerability
Authors: Zulli Alessandro , Chan Elana M. G. , Boehm Alexandria B. 
Published: July 2024

AbstractWastewater-based epidemiology, which seeks to assess disease occurrence in communities through measurements of infectious disease biomarkers in wastewater, may represent a valuable tool for understanding occurrence of hepatitis A infections in communities. In this study, we measured concentrations ofHepatovirus A(HAV) RNA, in samples from 191 wastewater treatment plants spanning 40 US states and the District of Columbia from September 2023 to June 2024 and compared the measurements with traditional measures of disease occurrence. Nationally, 13.76% of the 21,602 wastewater samples were positive for HAV RNA, and both concentrations and positivity rates were associated with NNDSS hepatitis A case data nationally (Kendall rank correlation coefficient = 0.20, concentrations; and 0.33, positivity rate; both p<0.05). We further demonstrated that higher rates of wastewater HAV detection were positively associated with socioeconomic indicators of vulnerability including homelessness and drug overdose deaths (both p<0.0001). Areas with above average levels of homelessness were 48% more likely to have HAV wastewater detections, while areas with above average levels of drug overdose deaths were 14% more likely to have HAV wastewater detections. Using more granular case data, we present a case study in the state of Maine that reinforces these results and suggests a potential lead time for wastewater over clinical case detection and exposure events. The ability to detect HAV RNA in wastewater before clinical cases emerge could allow public health officials to implement targeted interventions like vaccination campaigns.ImportanceDespite the existence of a highly effective vaccine for Hepatitis A, outbreaks in vulnerable populations remain common. The disease can be asymptomatic or subclinical, and disproportionately impacts populations with inadequate access to healthcare, leading to a severe underestimation of the occurrence of this viral infection. This study investigates the potential for wastewater measurements of biomarkers of the causative agent of hepatitis A (HAV RNA) to provide insights into disease occurrence. Results highlight the potential for wastewater-based epidemiology to be a complementary tool to traditional surveillance for monitoring and controlling HAV transmission.