bluuebunny/crossref_metadata_2025 huggingface dataset:
Bringing home the benefits: do pro-family employee benefits mitigate the risk of depression from competing workplace and domestic labor roles?
Authors: Platt Jonathan M , Bates Lisa , Jager Justin , McLaughlin Katie A , Keyes Katherine M
Published: April 2024

Despite significant historical progress toward sex/gender parity in employment status in the United States, women remain more likely to provide domestic labor, creating role competition which may increase depression symptoms. Pro-family employee benefits may minimize the stress of competing roles. We tested whether depressive symptoms were higher among women with competing roles versus without competing roles and whether this effect was greater among women without (vs with) pro-family benefits. Data included employed women (n = 9884 person-years) surveyed across 4 waves (2010, 2015, 2017, and 2019) of the National Longitudinal Survey 1997. Depression symptoms were measured with the 5-item short version of the Mental Health Inventory (MHI-5). The effect of interaction between competing roles and pro-family employee benefits on depressive symptoms was also compared with that of non–family-related benefits, using marginal structural models to estimate longitudinal effects in the presence of time-varying confounding. MHI-5 scores were 0.56 points higher (95% CI, 0.15-0.97) among women in competing roles (vs not). Among women without pro-family benefits, competing roles increased MHI-5 scores by 6.10 points (95% CI, 1.14-11.1). In contrast, there was no association between competing roles and MHI-5 scores among women with access to these benefits (MHI-5 difference = 0.44; 95% CI, −0.2 to 1.0). Results were similar for non–family-related benefits. Dual workplace and domestic labor role competition increases women’s depression symptoms, though broad availability of workplace benefits may attenuate that risk.

This article is part of a Special Collection on Mental Health.
Unraveling the molecular mechanism of the interaction between cyclodextrin-based nanoparticles (CDNPs) and paroxetine hydrochloride
Authors: Doan Anh Thi Ngoc , Sakurai Kazuo
Published: April 2024

Cyclodextrin-based nanoparticles (CDNPs) have shown promise as versatile carriers for improving drug delivery systems. This study investigates the binding constants governing the interaction between paroxetine hydrochloride (PRX) and β-cyclodextrin (βCD) and β-cyclodextrin epichlorohydrin polymer (βCDNP), utilizing a range of methodologies. The findings demonstrate enhanced binding affinity between PRX and βCDNP, offering insights into the binding behavior. Furthermore, the presence of a 2:1 βCD-PRX inclusion complex within the polymer suggests potential applications in drug delivery, particularly for improving solubility and stability of poorly water-soluble drugs. These results contribute to our understanding of host-guest interactions, with implications for enhancing therapeutic efficacy and patient outcomes. The study offers valuable insights into supramolecular chemistry and pharmaceutical sciences, paving the way for more effective drug delivery systems.
Integration of graph network with kernel SVM and logistic regression for identification of biomarkers in SCA12 and its diagnosis
Authors: Agrawal Snigdha , Agrawal Ramesh Kumar , Kumaran S Senthil , Rana Bharti , Srivastava Achal Kumar
Published: April 2024

Spinocerebellar ataxia type 12 is a hereditary and neurodegenerative illness commonly found in India. However, there is no established noninvasive automatic diagnostic system for its diagnosis and identification of imaging biomarkers. This work proposes a novel four-phase machine learning–based diagnostic framework to find spinocerebellar ataxia type 12 disease–specific atrophic-brain regions and distinguish spinocerebellar ataxia type 12 from healthy using a real structural magnetic resonance imaging dataset. Firstly, each brain region is represented in terms of statistics of coefficients obtained using 3D-discrete wavelet transform. Secondly, a set of relevant regions are selected using a graph network–based method. Thirdly, a kernel support vector machine is used to capture nonlinear relationships among the voxels of a brain region. Finally, the linear relationship among the brain regions is captured to build a decision model to distinguish spinocerebellar ataxia type 12 from healthy by using the regularized logistic regression method. A classification accuracy of 95% and a harmonic mean of precision and recall, i.e. F1-score of 94.92%, is achieved. The proposed framework provides relevant regions responsible for the atrophy. The importance of each region is captured using Shapley Additive exPlanations values. We also performed a statistical analysis to find volumetric changes in spinocerebellar ataxia type 12 group compared to healthy. The promising result of the proposed framework shows that clinicians can use it for early and timely diagnosis of spinocerebellar ataxia type 12.
Hereditary and cortical morphological biomarker of sensitivity to reward in short-term withdrawal methamphetamine abusers
Authors: Yang Longtao , Yang Wenhan , Tang Fei , Yuan Kai , Zhang Jun , Liu Jun
Published: April 2024

Higher sensitivity to reward (SR) and weaker sensitivity to punishment (SP) construct the fundamental craving characteristics of methamphetamine abuse. However, few studies have appraised relationships between SR/SP (SR or SP) and cortical morphological alterations in methamphetamine abusers and whether hereditary factors take effects on SR/SP is unclear. Based on surface-based morphometric analysis, cortical discrepancy was investigated between 38 methamphetamine abusers and 37 healthy controls. Within methamphetamine abusers, correlation profiling was performed to discover associations among aberrant neuroimaging substrates, SR, SP, and craving. According to nine single nucleotide polymorphism sites of dopamine-related genes, we conducted univariate general linear model to find different effects of genotypes on cortical alterations and SR/SP/craving (SR, SP, or craving). Ultimately, mediation analyses were conducted among single nucleotide polymorphism sites, SR/SP/craving, and cortical morphological alterations to discover their association pathways. Compared to healthy controls, thinner cortices in inferior temporal gyrus, lateral orbitofrontal cortex, medial orbitofrontal cortex, inferior parietal lobule, and lateral occipital cortex in the left hemisphere were found in methamphetamine abusers (P < 0.05, family-wise error corrected). Cortical thickness in the inferior temporal gyrus was negatively correlated with SR scores. We found that rs1800497 A-containing genotypes had lower cortical thickness in the left inferior parietal lobule than the GG genotype. The rs5751876 had effects on SR scores. This study would provide convincing biomarkers for SR in methamphetamine abusers and offer potential genetic targets for personalizing relapse prevention.
Network-wise analysis of movie-specific information in dynamic functional connectivity using COBE
Authors: Mittal Priyanka , Sao Anil K , Biswal Bharat , Di Xin , Dileep Aroor Dinesh
Published: April 2024

Movie watching during functional magnetic resonance imaging has emerged as a promising tool to measure the complex behavior of the brain in response to a stimulus similar to real-life situations. It has been observed that presenting a movie (sequence of events) as a stimulus will lead to a unique time course of dynamic functional connectivity related to movie stimuli that can be compared across the participants. We assume that the observed dynamic functional connectivity across subjects can be divided into following 2 components: (i) specific to a movie stimulus (depicting group-level behavior in functional connectivity) and (ii) individual-specific behavior (not necessarily common across the subjects). In this work, using the dynamic time warping distance measure, we have shown the extent of similarity between the temporal sequences of functional connectivity while the underlying movie stimuli were same and different. Further, the temporal sequence of functional connectivity patterns related to a movie is enhanced by suppressing the subject-specific components of dynamic functional connectivity using common and orthogonal basis extraction. Quantitative analysis using the F-ratio measure reveals significant differences in dynamic functional connectivity within the somatomotor network and default mode network, as well as between the occipital network and somatomotor networks.
Neural correlates of musical familiarity: a functional magnetic resonance study
Authors: Li Qiang , Liu Guangyuan , Zhang Yuan , Wu Junhua , Huang Rong
Published: April 2024

Existing neuroimaging studies on neural correlates of musical familiarity often employ a familiar vs. unfamiliar contrast analysis. This singular analytical approach reveals associations between explicit musical memory and musical familiarity. However, is the neural activity associated with musical familiarity solely related to explicit musical memory, or could it also be related to implicit musical memory? To address this, we presented 130 song excerpts of varying familiarity to 21 participants. While acquiring their brain activity using functional magnetic resonance imaging (fMRI), we asked the participants to rate the familiarity of each song on a five-point scale. To comprehensively analyze the neural correlates of musical familiarity, we examined it from four perspectives: the intensity of local neural activity, patterns of local neural activity, global neural activity patterns, and functional connectivity. The results from these four approaches were consistent and revealed that musical familiarity is related to the activity of both explicit and implicit musical memory networks. Our findings suggest that: (1) musical familiarity is also associated with implicit musical memory, and (2) there is a cooperative and competitive interaction between the two types of musical memory in the perception of music.
Long-term clinicopathological characteristics of TAFRO syndrome and its relapse: a case series study
Authors: Yoshimura Yusuke , Mizuno Hiroki , Ikuma Daisuke , Yamanouchi Masayuki , Sekine Akinari , Suwabe Tatsuya , Oba Yuki , Kurihara Shigekazu , Sugimoto Hisashi , Inoue Noriko , Yoshimoto Masatoshi , Tanimizu Hikaru , Tsunoda Susumu , Iijima Momoko , Kono Kei , Kinowaki Keiichi , Ohashi Kenichi , Takazawa Yutaka , Hasegawa Eiko , Ubara Yoshifumi , Sawa Naoki
Published: April 2024

Introduction

This study aimed to analyze the clinical course of TAFRO syndrome in patients through extended follow-up, focusing on recurrent cases and long-term remission.

Methods

This was a retrospective case series study. We assessed the clinical course of patients diagnosed with TAFRO syndrome between January 2012 and September 2022 at Toranomon Hospital or Toranomon Hospital Kajigaya, excluding those patients who died during the initial hospitalization.

Results

Twelve patients were included. Baseline characteristics, laboratory findings, treatment modalities, and outcomes were assessed. During the median follow-up period of 1474 days, two patients experienced recurrence following a reduction in tocilizumab (TCZ) dose, whereas two achieved remission for >400 days without TCZ treatment. The remaining eight patients maintained remission under the continued TCZ therapy. Recurrence diagnosis was complicated by the non-simultaneous presentation of the five manifestations of TAFRO syndrome. The patients who experienced recurrence showed milder manifestations and faster recovery than the initial onset. Glomerular endotheliopathy was evident in kidney biopsies during recurrence, which was similar to the initial presentation. In a case where only inflammation preceded other manifestation, a kidney biopsy was pivotal in distinguishing TAFRO syndrome relapse from other inflammatory conditions such as infection. Pretreatment serum IL-6 levels were within the reference range only in patients who experienced long-term remission without TCZ treatment.

Conclusions

This is the first study to perform kidney biopsies on recurrent TAFRO cases, highlighting recurrence after TCZ dosage reduction, non-simultaneous manifestation of symptoms, the utility of kidney biopsies in recurrence diagnosis, and potential non-IL-6 pathogenesis factors. Pretreatment serum IL-6 levels may help identify patients suitable for maintenance therapy without TCZ. Further investigation is warranted to identify stratified treatment approaches based on individual etiologic factors.
Gene expression and ultra-structural evidence for metabolic derangement in the primary mitral regurgitation heart
Authors: Kane Mariame Selma , Juncos Juan Xavier Masjoan , Manzoor Shajer , Grenett Maximiliano , Oh Joo-Yeun , Pat Betty , Ahmed Mustafa I , Lewis Clifton , Davies James E , Denney Thomas S , McConathy Jonathan , Dell’Italia Louis J
Published: April 2024

Aims

Chronic neurohormonal activation and haemodynamic load cause derangement in the utilization of the myocardial substrate. In this study, we test the hypothesis that the primary mitral regurgitation (PMR) heart shows an altered metabolic gene profile and cardiac ultra-structure consistent with decreased fatty acid and glucose metabolism despite a left ventricular ejection fraction (LVEF) > 60%.

Methods and results

Metabolic gene expression in right atrial (RA), left atrial (LA), and left ventricular (LV) biopsies from donor hearts (n = 10) and from patients with moderate-to-severe PMR (n = 11) at surgery showed decreased mRNA glucose transporter type 4 (GLUT4), GLUT1, and insulin receptor substrate 2 and increased mRNA hexokinase 2, O-linked N-acetylglucosamine transferase, and O-linked N-acetylglucosaminyl transferase, rate-limiting steps in the hexosamine biosynthetic pathway. Pericardial fluid levels of neuropeptide Y were four-fold higher than simultaneous plasma, indicative of increased sympathetic drive. Quantitative transmission electron microscopy showed glycogen accumulation, glycophagy, increased lipid droplets (LDs), and mitochondrial cristae lysis. These findings are associated with increased mRNA for glycogen synthase kinase 3β, decreased carnitine palmitoyl transferase 2, and fatty acid synthase in PMR vs. normals. Cardiac magnetic resonance and positron emission tomography for 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) uptake showed decreased LV [18F]FDG uptake and increased plasma haemoglobin A1C, free fatty acids, and mitochondrial damage-associated molecular patterns in a separate cohort of patients with stable moderate PMR with an LVEF > 60% (n = 8) vs. normal controls (n = 8).

Conclusion

The PMR heart has a global ultra-structural and metabolic gene expression pattern of decreased glucose uptake along with increased glycogen and LDs. Further studies must determine whether this presentation is an adaptation or maladaptation in the PMR heart in the clinical evaluation of PMR.
Prevalence and predictive features of metabolic dysfunction-associated steatotic liver disease in type 1 diabetes
Authors: Fuhri Snethlage Coco M , Meijnikman Abraham S , Mak Anne Linde , Rampanelli Elena , Voermans Bas , Callender Cengiz A K , de Groen Pleun , Roep Bart O , van Raalte Daniël H , Knop Filip K , Holleboom Adriaan G , Nieuwdorp Max , Hanssen Nordin M J
Published: April 2024

Aims/hypothesis

The prevalence and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) in type 1 diabetes remain unclear. Therefore, we investigated the prevalence and severity of MASLD in type 1 diabetes and assessed which clinical features are most important in predicting MASLD severity.

Methods

A total of 453 individuals with type 1 diabetes (41.6 ± 15.0 years, 64% female, body mass index [BMI] 25.4 ± 4.2 kg/m2, and HbA1c 55.6 ± 12 mmol/mol) underwent vibration-controlled transient elastography (VCTE), with a controlled attenuation parameter (CAP) score for steatosis (≥280.0 dB/m) and a liver stiffness measurement (LMS) for fibrosis (≥8.0 kPa). A machine learning Extra-Trees classification model was performed to assess the predictive power of the clinical features associated with type 1 diabetes with respect to steatosis and fibrosis.

Results

The prevalence of hepatic steatosis and fibrosis was 9.5% (95% CI, 6.8-12.2) and 3.5% (95% CI, 1.8-5.2). Higher LMS was associated with a longer duration of type 1 diabetes (median 30.5 [IQR 18.0-39.3] years vs 15.0 [IQR 6.0-27.0] years), and individuals were older, had a higher BMI (mean 27.8 ± 5.2 vs 25.3 ± 4.1 kg/m2), and a higher CAP score (mean 211.4 ± 51.7 dB/m vs 241.4 ± 75.6 dB/m). The most important predictive features of fibrosis were duration of type 1 diabetes, age, and systolic blood pressure, with a mean ± SD area under the curve of 0.73 ± 0.03.

Conclusion

Individuals with type 1 diabetes and high blood pressure, older age, higher BMI, and longer duration of disease could be considered at high-risk for developing MASLD.
Group boundaries in the Netherlands: how religion and ethnicity matter for social integration
Authors: Arnold Lena , Fleischmann Fenella
Published: April 2024

Both religion and ethnicity have been found to be important group boundaries for immigrants’ social integration into European societies. However, since both characteristics often overlap, their unique influences remain understudied. Conceptualizing social integration as a form of boundary work, this study aims to disentangle religious and ethnic group distinctions and to examine how they matter for immigrants’ contact with members of the Dutch majority group. Relying on data from four large immigrant groups in the Netherlands, that allows exploiting religious diversity within ethnic groups, we describe differences in contact with Dutch majority members between 13 ethno-religious group combinations, and we perform multiple-group SEM across the 10 largest combinations. Results indicate that while the importance of religious affiliation and ethnicity is group-specific, the strongest boundary for immigrants’ contact with members of the Dutch majority group is that between the religious and non-religious. The relative importance of religion and ethnicity for social integration is explained both by immigrants’ own maintenance of group boundaries and their perception of boundary permeability.
A naturally occurring canine model of syndromic congenital microphthalmia
Authors: Murgiano Leonardo , Banjeree Esha , O'Connor Cynthia , Miyadera Keiko , Werner Petra , Niggel Jessica K , Aguirre Gustavo D , Casal Margret L
Published: April 2024

In humans, the prevalence of congenital microphthalmia is estimated to be 0.2–3.0 for every 10,000 individuals, with nonocular involvement reported in ∼80% of cases. Inherited eye diseases have been widely and descriptively characterized in dogs, and canine models of ocular diseases have played an essential role in unraveling the pathophysiology and development of new therapies. A naturally occurring canine model of a syndromic disorder characterized by microphthalmia was discovered in the Portuguese water dog. As nonocular findings included tooth enamel malformations, stunted growth, anemia, and thrombocytopenia, we hence termed this disorder Canine Congenital Microphthalmos with Hematopoietic Defects. Genome-wide association study and homozygosity mapping detected a 2 Mb candidate region on canine chromosome 4. Whole-genome sequencing and mapping against the Canfam4 reference revealed a Short interspersed element insertion in exon 2 of the DNAJC1 gene (g.74,274,883ins[T70]TGCTGCTTGGATT). Subsequent real-time PCR-based mass genotyping of a larger Portuguese water dog population found that the homozygous mutant genotype was perfectly associated with the Canine Congenital Microphthalmos with Hematopoietic Defects phenotype. Biallelic variants in DNAJC21 are mostly found to be associated with bone marrow failure syndrome type 3, with a phenotype that has a certain degree of overlap with Fanconi anemia, dyskeratosis congenita, Shwachman–Diamond syndrome, Diamond–Blackfan anemia, and reports of individuals showing thrombocytopenia, microdontia, and microphthalmia. We, therefore, propose Canine Congenital Microphthalmos with Hematopoietic Defects as a naturally occurring model for DNAJC21-associated syndromes.
Insights from Hi-C data regarding the Pacific salmon louse (Lepeophtheirus salmonis) sex chromosomes
Authors: Flores Anne-Marie , Christensen Kris A , Siah Ahmed , Koop Ben F
Published: April 2024

Salmon lice, Lepeophtheirus salmonis (family Caligidae), are ectoparasites that have negatively impacted the salmon aquaculture industry and vulnerable wild salmon populations. Researchers have studied salmon lice to better understand their biology to develop effective control strategies. In this study, we updated the chromosome-level reference genome assembly of the Pacific subspecies of L. salmonis using Hi-C data. The previous version placed contigs/scaffolds using an Atlantic salmon louse genetic map. By utilizing Hi-C data from Pacific salmon lice, we were able to properly assign locations to contigs/scaffolds previously unplaced or misplaced. This resulted in a more accurate genome assembly and a more comprehensive characterization of the sex chromosome unique to females (W). We found evidence that the same ZW-ZZ mechanism is common in both Atlantic and Pacific subspecies of salmon lice using PCR assays. The W chromosome was approximately 800 kb in size, which is ∼30 times smaller than the Z chromosome (24 Mb). The W chromosome contained 61 annotated genes, including 32 protein-coding genes, 27 long noncoding RNA (lncRNA) genes, and 2 pseudogenes. Among these 61 genes, 39 genes shared homology to genes found on other chromosomes, while 20 were unique to the W chromosome. Two genes of interest on the W chromosome, prohibitin-2 and kinase suppressor of ras-2, were previously identified as potential sex-linked markers in the salmon louse. However, we prioritized the 20 unique genes on the W chromosome as sex-determining candidates. This information furthers our understanding of the biology of this ectoparasite and may help in the development of more effective management strategies.
Perception of congenital cardiac surgery as a career choice among cardiothoracic surgery trainees in the United Kingdom
Authors: George Joseph , Lotto Attilio
Published: April 2024

OBJECTIVES

Our goal was to evaluate interest among trainees in pursuing congenital cardiac surgery (CCS) as a sub-specialty career and probe for reasons in decline in interest.

METHODS

An anonymized, voluntary survey of cardiothoracic surgical trainees across the United Kingdom and Ireland was conducted from October 2020 to December 2020. The questionnaire included demographics, congenital experience and career intentions.

RESULTS

A total of 43 respondents from all training regions responded with a response rate of 36%. A total of 28% reported having no access to a congenital cardiac unit in their training region, reflecting that 4 out of the 14 regions do not have a congenital unit. Although only 18% of trainees have undertaken a placement, a large proportion (74%) have considered a career in CCS, predominantly (50%) before entering training or in the first half of the training programme (38%). Reasons for not pursuing included discouragement by colleagues (42%) and concerns regarding the training pathway, citing, among other reasons, length of training, limited exposure to operations and uncertainty about career progression. Respondents suggested improvements to the training programme, including increasing exposure and early mentoring and steps to dispel unduly negative perceptions about the specialty.

CONCLUSIONS

A large proportion of cardiothoracic trainees have a negative perception of CCS in terms of career and training. Interest wanes substantially after entry into the United Kingdom cardiothoracic training programme for several reasons. As well as short-term measures to improve exposure to CCS and structure of training, there has to be long-term planning to improve perception about this sub-specialty at all levels.
Tricuspid valve repair for infective endocarditis
Authors: Lorenz Veronica , Mastrobuoni Stefano , Aphram Gaby , Pettinari Matteo , de Kerchove Laurent , El Khoury Gebrine
Published: April 2024

OBJECTIVES

The progressive increase in the use of implantable electronic devices, vascular access for dialysis and the increased life expectancy of patients with congenital heart diseases has led in recent years to a considerable number of right-side infective endocarditis, especially of the tricuspid valve (TV). Although current guidelines recommend TV repair for native tricuspid valve endocarditis (TVE), the percentage of valve replacements remains very high in numerous studies. The aim of our study is to analyse our experience in the treatment of TVE with a reparative approach.

METHODS

This case series includes all the patients who underwent surgery for acute or healed infective endocarditis on the native TV, at the Cliniques Universitaires Saint-Luc (Bruxelles, Belgium) between February 2001 and December 2020.

RESULTS

Thirty-one patients were included in the study. Twenty-eight (90.3%) underwent TV repair and 3 (9.7%) had a TV replacement with a mitral homograft. The repair group was divided into 2 subgroups, according to whether a patch was used during surgery or not. Hospital mortality was 33.3% (n = 1) for the replacement group and 7.1% (n = 2) for repair (P = 0.25). Overall survival at 10 years was 75.6% [95% confidence interval (CI): 52–89%]. Further, freedom from reoperation on the TV at 10 years was 59.3% (95% CI: 7.6–89%) vs 93.7% (95% CI: 63–99%) (P = 0.4) for patch repair and no patch use respectively. Freedom from recurrent endocarditis at 10 years was 87% (95% CI: 51–97%).

CONCLUSIONS

Considering that TVE is more common in young patients, a repair-oriented approach should be considered as the first choice. In the case of extremely damaged valves, the use of pericardial patch is a valid option. If repair is not feasible, the use of a mitral homograft is an additional useful solution to reduce the prosthetic material.
An audit of the continuation and review of intensive care unit (ICU)-initiated medications post ICU discharge
Authors: Kearney M , Leamy D , Sahm L J
Published: April 2024

Introduction

Medication errors at transitions of care have widely been reported and the transition of a patient from intensive care unit (ICU) to ward level care has additional risk for error due to the complexity of the cohort. The continuation of ICU-initiated medications at ward level has been associated with adverse drug events, and error mitigation strategies need to be implemented at the point of discharge from ICU to facilitate deprescribing and medication optimisation. Pharmacists are in an excellent position to facilitate this medication optimisation at the point of ICU transfer.

Aim

This study aimed to evaluate the frequency that ICU-initiated medications are continued on discharge from ICU and subsequently reviewed at ward level in a large teaching hospital.

Methods

An audit was conducted as a prospective observational study over the period of June and July 2023. A pharmacist reviewed kardexes of patients that had been discharged from ICU to determine the prevalence of ICU-initiated medications that were continued post discharge. Medications continued were documented using an Excel spreadsheet on a password-protected computer. A pharmacist followed patients at day 7 post ICU discharge and an audit was conducted to document if these medications had been reviewed by primary teams. A medication was deemed to be reviewed by a primary team if discontinued on the kardex, a dose altered on the kardex or reference made to the medication in the medical notes. All patients discharged from ICU to ward level care were eligible to be included in the study.

Results

In total, 53 patients were eligible to be included in the study, of which 51 had ICU-initiated medications continued on discharge. No class of medication was found to be reviewed for all patients discharged on that class of medication. Over half of patients (52.9%) had stress ulcer prophylaxis medications continued, 39.2% had opioids continued and 33.3% had anti-delirium medications continued. No surgical patient had anti-delirium medications reviewed at ward level and surgical patients were found to be the largest cohort discharged on opioids but not reviewed at ward level.

Conclusion

This study has highlighted that not only are ICU-initiated mediations continued on discharge from ICU, but also that a high proportion of these medications are not reviewed at ward level by primary teams. This has further shown the requirement for pharmacist review and verification of kardexes prior to ICU discharge and the implementation of deprescribing protocols. The main limitation of the study was the small sample size of patients discharged from ICU during the study period. Future studies could focus on the impact that a pharmacist-led quality improvement initiative would have on the continuation and review of ICU-initiated medications on discharge from the ICU and the audit repeated over a longer period of time.
Rotavirus Hospitalization in Early Childhood: Fine Motor Skills and Cognition at 6 Years Old in a Population-Based Cohort Study
Authors: Ha Eun Kyo , Kim Ju Hee , Han Boeun , Shin Jeewon , Lee Eun , Rhie Seonkyeong , Lee Won Seok , Lee Soonchul , Han Man Yong
Published: April 2024

Rotavirus is linked to severe childhood gastroenteritis and neurological complications, but its impact on neurodevelopment remains uncertain. We examined data from 1 420 941 Korean children born between 2009 and 2011, using the Korean National Health Insurance System. We assessed neurodevelopmental outcomes at age 6 years using the validated Korean Developmental Test, covering 6 major domains, with propensity score-based inverse probability weighting including consideration of covariates sex, birth weight, changes in body weight from birth to 4–6 months of age, head circumference at 4–6 months of age, residence at birth, economic status, infant feeding types, and birth year. The main analysis that encompassed 5451 children with rotavirus hospitalization and 310 874 unexposed individuals revealed heightened odds of suspected delays in fine motor skills and cognition among exposed children. Our results suggest an association between rotavirus-related hospitalization in infancy and suspected delays in fine motor function and cognition in 6 year olds.
Rural Underemployment and Urbanisation: Insights from a 9-year Panel from Malawi
Authors: Van Cappellen Hanne , De Weerdt Joachim
Published: April 2024

Rural labour markets in Africa are frequently characterised by underemployment, with farmers unable to fully deploy throughout the year one of their most important assets—their labour. Using a nine-year panel data set on 1,407 working-age adults from rural Malawi, we document changes in rural underemployment over this period and how they are associated with urbanisation. Nearby urban growth is linked to increased hours worked in casual labour (ganyu) and in non-agricultural sectors, at the expense of work on the household farm. Improved urban access is also associated with a small increase in wage labour and, at the intensive margin, with hours supplied in household enterprises. We draw lessons from these results for policies, investments and interventions to leverage urban growth for rural development.
Mixed methods assessment of the influence of demographics on medical advice of ChatGPT
Authors: Andreadis Katerina , Newman Devon R , Twan Chelsea , Shunk Amelia , Mann Devin M , Stevens Elizabeth R
Published: April 2024

Objectives

To evaluate demographic biases in diagnostic accuracy and health advice between generative artificial intelligence (AI) (ChatGPT GPT-4) and traditional symptom checkers like WebMD.

Materials and Methods

Combination symptom and demographic vignettes were developed for 27 most common symptom complaints. Standardized prompts, written from a patient perspective, with varying demographic permutations of age, sex, and race/ethnicity were entered into ChatGPT (GPT-4) between July and August 2023. In total, 3 runs of 540 ChatGPT prompts were compared to the corresponding WebMD Symptom Checker output using a mixed-methods approach. In addition to diagnostic correctness, the associated text generated by ChatGPT was analyzed for readability (using Flesch-Kincaid Grade Level) and qualitative aspects like disclaimers and demographic tailoring.

Results

ChatGPT matched WebMD in 91% of diagnoses, with a 24% top diagnosis match rate. Diagnostic accuracy was not significantly different across demographic groups, including age, race/ethnicity, and sex. ChatGPT's urgent care recommendations and demographic tailoring were presented significantly more to 75-year-olds versus 25-year-olds (P < .01) but were not statistically different among race/ethnicity and sex groups. The GPT text was suitable for college students, with no significant demographic variability.

Discussion

The use of non-health-tailored generative AI, like ChatGPT, for simple symptom-checking functions provides comparable diagnostic accuracy to commercially available symptom checkers and does not demonstrate significant demographic bias in this setting. The text accompanying differential diagnoses, however, suggests demographic tailoring that could potentially introduce bias.

Conclusion

These results highlight the need for continued rigorous evaluation of AI-driven medical platforms, focusing on demographic biases to ensure equitable care.
Development and external validation of deep learning clinical prediction models using variable-length time series data
Authors: Bashiri Fereshteh S , Carey Kyle A , Martin Jennie , Koyner Jay L , Edelson Dana P , Gilbert Emily R , Mayampurath Anoop , Afshar Majid , Churpek Matthew M
Published: April 2024

Objectives

To compare and externally validate popular deep learning model architectures and data transformation methods for variable-length time series data in 3 clinical tasks (clinical deterioration, severe acute kidney injury [AKI], and suspected infection).

Materials and Methods

This multicenter retrospective study included admissions at 2 medical centers that spanned 2007-2022. Distinct datasets were created for each clinical task, with 1 site used for training and the other for testing. Three feature engineering methods (normalization, standardization, and piece-wise linear encoding with decision trees [PLE-DTs]) and 3 architectures (long short-term memory/gated recurrent unit [LSTM/GRU], temporal convolutional network, and time-distributed wrapper with convolutional neural network [TDW-CNN]) were compared in each clinical task. Model discrimination was evaluated using the area under the precision-recall curve (AUPRC) and the area under the receiver operating characteristic curve (AUROC).

Results

The study comprised 373 825 admissions for training and 256 128 admissions for testing. LSTM/GRU models tied with TDW-CNN models with both obtaining the highest mean AUPRC in 2 tasks, and LSTM/GRU had the highest mean AUROC across all tasks (deterioration: 0.81, AKI: 0.92, infection: 0.87). PLE-DT with LSTM/GRU achieved the highest AUPRC in all tasks.

Discussion

When externally validated in 3 clinical tasks, the LSTM/GRU model architecture with PLE-DT transformed data demonstrated the highest AUPRC in all tasks. Multiple models achieved similar performance when evaluated using AUROC.

Conclusion

The LSTM architecture performs as well or better than some newer architectures, and PLE-DT may enhance the AUPRC in variable-length time series data for predicting clinical outcomes during external validation.
Limits to species’ range: the tension between local and global adaptation
Authors: Barton Nicholas
Published: April 2024

We know that heritable variation is abundant, and that selection causes all but the smallest populations to rapidly shift beyond their original trait distribution. So then, what limits the range of a species? There are physical constraints and also population genetic limits to the effectiveness of selection, ultimately set by population size. Global adaptation, where the same genotype is favoured over the whole range, is most efficient when based on a multitude of weakly selected alleles and is effective even when local demes are small, provided that there is some gene flow. In contrast, local adaptation is sensitive to gene flow and may require alleles with substantial effect. How can populations combine the advantages of large effective size with the ability to specialise into local niches? To what extent does reproductive isolation help resolve this tension? I address these questions using eco-evolutionary models of polygenic adaptation, contrasting discrete demes with continuousspace.
Scoping Review of Music Interventions Aimed at Improving Reading Skills in Children with Specific Learning Disorders in Reading
Authors: Lewis Jenny Diouf , Kim Soo Ji
Published: April 2024

An emerging body of research utilizes music in the treatment of children with specific learning disorders in reading. However, greater understanding of music interventions is necessary for efficient application of music to address children’s specific reading needs. Therefore, this scoping review aimed to identify the key musical concepts used to improve reading skills. Intervention studies were identified through online searches of databases and hand searching of primary journals in music therapy, and 12 studies met the inclusion criteria. For the 12 studies, auditory processing, phonological processing, and temporal processing were the underlying mechanisms identified in the interventions. Most of the interventions presented rhythmic activities for the purpose of improving reading accuracy. The results of this study highlight the lack of specific descriptions for the musical elements used within music interventions targeting reading skills. In addition, due to the diversity of the terms used to describe the music interventions, it was difficult to compare the effectiveness of these interventions on reading accuracy, comprehension skills, and fluency. Therefore, future studies are needed to articulate clear rationales for how musical elements can be used in music interventions to treat specific reading disabilities in children.
The molecular basis of CONSTITUTIVE PHOTOMORPHOGENIC1 action during photomorphogenesis
Authors: Zhou Hua , Deng Xing Wang
Published: April 2024

CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1), a repressor of seedling photomorphogenesis, is tightly controlled by light. In Arabidopsis, COP1 primarily acts as a part of large E3 ligase complexes and targets key light-signaling factors for ubiquitination and degradation. Upon light perception, the action of COP1 is precisely modulated by active photoreceptors. During seedling development, light plays a predominant role in modulating seedling morphogenesis, including inhibition of hypocotyl elongation, cotyledon opening and expansion, and chloroplast development. These visible morphological changes evidently result from networks of molecular action. In this review, we summarize current knowledge about the molecular role of COP1 in mediating light-controlled seedling development.
RHO OF PLANTS signalling and the activating ROP GUANINE NUCLEOTIDE EXCHANGE FACTORS: specificity in cellular signal transduction in plants
Authors: Denninger Philipp
Published: April 2024

Every cell constantly receives signals from its neighbours or the environment. In plants, most signals are perceived by RECEPTOR-LIKE KINASEs (RLKs) and then transmitted into the cell. The molecular switches RHO OF PLANTS (ROP) are critical proteins for polar signal transduction and regulate multiple cell polarity processes downstream of RLKs. Many ROP-regulating proteins and scaffold proteins of the ROP complex are known. However, the spatiotemporal ROP signalling complex composition is not yet understood. Moreover, how specificity is achieved in different ROP signalling pathways within one cell still needs to be determined. This review gives an overview of recent advances in ROP signalling and how specificity by downstream scaffold proteins can be achieved. The composition of the ROP signalling complexes is discussed, focusing on the possibility of the simultaneous presence of ROP activators and inactivators within the same complex to balance ROP activity. Furthermore, this review highlights the function of plant-specific ROP GUANINE NUCLEOTIDE EXCHANGE FACTORS polarizing ROP signalling and defining the specificity of the initiated ROP signalling pathway.
Machine Learning Data Augmentation Strategy for Electron Energy Loss Spectroscopy: Generative Adversarial Networks
Authors: del-Pozo-Bueno Daniel , Kepaptsoglou Demie , Ramasse Quentin M , Peiró Francesca , Estradé Sònia
Published: April 2024

Recent advances in machine learning (ML) have highlighted a novel challenge concerning the quality and quantity of data required to effectively train algorithms in supervised ML procedures. This article introduces a data augmentation (DA) strategy for electron energy loss spectroscopy (EELS) data, employing generative adversarial networks (GANs). We present an innovative approach, called the data augmentation generative adversarial network (DAG), which facilitates data generation from a very limited number of spectra, around 100. Throughout this study, we explore the optimal configuration for GANs to produce realistic spectra. Notably, our DAG generates realistic spectra, and the spectra produced by the generator are successfully used in real-world applications to train classifiers based on artificial neural networks (ANNs) and support vector machines (SVMs) that have been successful in classifying experimental EEL spectra.
Hall-magnetohydrodynamic simulations of X-ray photoevaporative protoplanetary disc winds
Authors: Sarafidou Eleftheria , Gressel Oliver , Picogna Giovanni , Ercolano Barbara
Published: April 2024

Understanding the evolution and dispersal via energetic stellar radiation of protoplanetary discs (PPDs) is a prominent challenge in astrophysics. It has been established that X-ray luminosity from the central protostar can significantly heat the surface of the disc, causing powerful photoevaporative winds that eject a considerable fraction of the disc’s mass. Recent work in the field has moreover shown the importance of global PPD simulations that simultaneously take into account non-ideal magnetohydrodynamic (MHD) effects and detailed thermochemistry. In this paper, we combine these two aspects and figure out how they interact. Focus is put on the Hall Effect (HE) and the impact it has on the overall field topology and mass-loss/accretion rates. Utilizing a novel X-ray temperature parametrization, we perform 2D-axisymmetric MHD simulations with the nirvana-iii fluid code, covering all non-ideal effects. We find that, in the aligned orientation, the HE causes prominent inward displacement of the poloidal field lines that increase the accretion rate through a laminar Maxwell stress. We find that outflows are mainly driven by photoevaporation – unless the magnetic field strength is considerable (i.e. βp ≤ 103) or the X-ray luminosity low enough (i.e. log LX ≤ 29.3). Inferred mass-loss rate are in the range of the expected values 10−8–$10^{-7}\, M_\odot \, {\rm yr}^{-1}$. Moreover, we performed pure hydrodynamic (HD) runs and compared them with the equivalent MHD runs. We concluded that the magnetic field does indeed contribute to the mass-loss rate, albeit only discernibly so for low enough LX (i.e. log LX ≤ 30.8).
SynDesign: web-based prime editing guide RNA design and evaluation tool for saturation genome editing
Authors: Park Jinman , Yu Goosang , Seo Sang-Yeon , Yang Jinyeong , Kim Hyongbum Henry
Published: April 2024

Saturation genome editing (SGE) enables in-depth functional evaluation of disease-associated genes and variants by generating all possible single nucleotide variants (SNVs) within a given coding region. Although prime editing can be employed for inducing these SNVs, designing efficient prime editing guide RNAs (pegRNAs) can be challenging and time-consuming. Here, we present SynDesign, an easy-to-use webtool for the design, evaluation, and construction precision pegRNA libraries for SGE with synonymous mutation markers. SynDesign offers a simple yet powerful interface that automates the generation of all feasible pegRNA designs for a target gene or variant of interest. The pegRNAs are selected using the state-of-the-art models to predict prime editing efficiencies for various prime editors and cell types. Top-scoring pegRNA designs are further enhanced using synonymous mutation markers which improve pegRNA efficiency by diffusing the cellular mismatch repair mechanism and serve as sequence markers for improved identification of intended edits following deep sequencing. SynDesign is expected to facilitate future research using SGE to investigate genes or variants of interest associated with human diseases. SynDesign is freely available at https://deepcrispr.info/SynDesign without a login process.
DNA-PK participates in pre-rRNA biogenesis independent of DNA double-strand break repair
Authors: Li Peng , Gai Xiaochen , Li Qilin , Yang Qianqian , Yu Xiaochun
Published: April 2024

Although DNA-PK inhibitors (DNA-PK-i) have been applied in clinical trials for cancer treatment, the biomarkers and mechanism of action of DNA-PK-i in tumor cell suppression remain unclear. Here, we observed that a low dose of DNA-PK-i and PARP inhibitor (PARP-i) synthetically suppresses BRCA-deficient tumor cells without inducing DNA double-strand breaks (DSBs). Instead, we found that a fraction of DNA-PK localized inside of nucleoli, where we did not observe obvious DSBs. Moreover, the Ku proteins recognize pre-rRNA that facilitates DNA-PKcs autophosphorylation independent of DNA damage. Ribosomal proteins are also phosphorylated by DNA-PK, which regulates pre-rRNA biogenesis. In addition, DNA-PK-i acts together with PARP-i to suppress pre-rRNA biogenesis and tumor cell growth. Collectively, our studies reveal a DNA damage repair-independent role of DNA-PK-i in tumor suppression.
Nextflow vs. plain bash: different approaches to the parallelization of SNP calling from the whole genome sequence data
Authors: Sztuka Marek , Kotlarz Krzysztof , Mielczarek Magda , Hajduk Piotr , Liu Jakub , Szyda Joanna
Published: April 2024

This study compared computational approaches to parallelization of an SNP calling workflow. The data comprised DNA from five Holstein-Friesian cows sequenced with the Illumina platform. The pipeline consisted of quality control, alignment to the reference genome, post-alignment, and SNP calling. Three approaches to parallelization were compared: (i) a plain Bash script in which a pipeline for each cow was executed as separate processes invoked at the same time, (ii) a Bash script wrapped in a single Nextflow process and (iii) a Nextflow script with each component of the pipeline defined as a separate process. The results demonstrated that on average, the multi-process Nextflow script performed 15–27% faster depending on the number of assigned threads, with the biggest execution time advantage over the plain Bash approach observed with 10 threads. In terms of RAM usage, the most substantial variation was observed for the multi-process Nextflow, for which it increased with the number of assigned threads, while RAM consumption of the other setups did not depend much on the number of threads assigned for computations. Due to intermediate and log files generated, disk usage was markedly higher for the multi-process Nextflow than for the plain Bash and for the single-process Nextflow.