bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beyond monopole electrostatics in regulating conformations of intrinsically disordered proteins
Authors: Phillips Michael , Muthukumar Murugappan , Ghosh Kingshuk 
Published: August 2024

Abstract
Conformations and dynamics of an intrinsically disordered protein (IDP) depend on its composition of charged and uncharged amino acids, and their specific placement in the protein sequence. In general, the charge (positive or negative) on an amino acid residue in the protein is not a fixed quantity. Each of the ionizable groups can exist in an equilibrated distribution of fully ionized state (monopole) and an ion-pair (dipole) state formed between the ionizing group and its counterion from the background electrolyte solution. The dipole formation (counterion condensation) depends on the protein conformation, which in turn depends on the distribution of charges and dipoles on the molecule. Consequently, effective charges of ionizable groups in the IDP backbone may differ from their chemical charges in isolation—a phenomenon termed charge-regulation. Accounting for the inevitable dipolar interactions, that have so far been ignored, and using a self-consistent procedure, we present a theory of charge-regulation as a function of sequence, temperature, and ionic strength. The theory quantitatively agrees with both charge reduction and salt-dependent conformation data of Prothymosin-alpha and makes several testable predictions. We predict charged groups are less ionized in sequences where opposite charges are well mixed compared to sequences where they are strongly segregated. Emergence of dipolar interactions from charge-regulation allows spontaneous coexistence of two phases having different conformations and charge states, sensitively depending on the charge patterning. These findings highlight sequence dependent charge-regulation and its potential exploitation by biological regulators such as phosphorylation and mutations in controlling protein conformation and function.
Antibiotics in inflammatory arthritis and background population one year before and after diagnosis: a nationwide drug utilization study
Authors: Kragsnaes Maja S , Risbo Nickolaj , Pedersen Jens Kristian , Obel Niels , Finckh Axel , Pedersen Alma B , Ellingsen Torkell 
Published: August 2024

Abstract

Objectives
To describe antibiotic use in patients with inflammatory arthritis (IA) and in the background population (BP) within one year before and after IA diagnosis.

Methods
Using data from Danish nationwide registries, we identified all adults with a first-time diagnosis of RA, PsA, or AS/spondyloarthritis (AS/SpA) from 2010 through 2018. For each IA patient, we randomly sampled 10 persons from the BP, matched on sex and birthdate. We calculated the prevalence (n [%]) of any antibiotic dispensing and the total antibiotic dispensing in the year before and after diagnosis.

Results
We identified 28 504 new-onset IA patients (RA, n = 16 130; PsA, n = 5988; AS/SpA, n = 6386) and 285 040 BP individuals. Within one year before diagnosis, the total amount of dispensed antibiotics was higher in both RA, PsA and As/SpA compared with the BP (prevalence rate ratios [PRR], 1.48 [1.46; 1.51]; 1.67 [1.62; 1.72]; 1.52 [1.47; 1.56], respectively). The amount increased with 22% in IA patients three months before diagnosis compared with the preceding three-month period. Although the prevalence of any antibiotic dispensing in IA patients decreased in the year following the diagnosis (IA; 40.6%), the total one-year antibiotic dispensing remained constant in RA (PRR 0.99 [0.97; 1.01]), decreased in PsA (0.91 [0.87; 0.94]) and increased in AS/SpA (1.08 [1.04; 1.12]) patients after diagnosis compared with before.

Conclusion
Antibiotics are more frequently dispensed to individuals developing IA compared with the BP. Antibiotic utilization patterns change after IA diagnosis with marked differences among IA subgroups.
Multitrait Genetic Analysis Identifies Novel Pleiotropic Loci for Depression and Schizophrenia in East Asians
Authors: Song Yingchao , Li Linzehao , Jiang Yue , Peng Bichen , Jiang Hengxuan , Chao Zhen , Chang Xiao 
Published: August 2024

Abstract

Background and Hypothesis
While genetic correlations, pleiotropic loci, and shared genetic mechanisms of psychiatric disorders have been extensively studied in European populations, the investigation of these factors in East Asian populations has been relatively limited.

Study Design
To identify novel pleiotropic risk loci for depression and schizophrenia (SCZ) in East Asians. We utilized the most comprehensive dataset available for East Asians and quantified the genetic overlap between depression, SCZ, and their related traits via a multitrait genome-wide association study. Global and local genetic correlations were estimated by LDSC and ρ-HESS. Pleiotropic loci were identified by the multitrait analysis of GWAS (MTAG).

Study Results
Besides the significant correlation between depression and SCZ, our analysis revealed genetic correlations between depression and obesity-related traits, such as weight, BMI, T2D, and HDL. In SCZ, significant correlations were detected with HDL, heart diseases and use of various medications. Conventional meta-analysis of depression and SCZ identified a novel locus at 1q25.2 in East Asians. Further multitrait analysis of depression, SCZ and related traits identified ten novel pleiotropic loci for depression, and four for SCZ.

Conclusions
Our findings demonstrate shared genetic underpinnings between depression and SCZ in East Asians, as well as their associated traits, providing novel candidate genes for the identification and prioritization of therapeutic targets specific to this population.
Effects of Plant Health-Protecting Product Applications on the Root-Associated Microbiota of Apple Saplings and Strawberries
Authors: Becker Maximilian F. , Deichmann Marion , Klueken A. Michael , Knief Claudia 
Published: August 2024

The root-associated microbiome has been of keen research interest due to its large potential for increasing plant performance. In agricultural systems, the use of plant health-protecting products (PHPPs) is essential for obtaining high yields and quality. Knowledge about the impact of PHPP applications on the root-associated microbiome remains limited, especially when applied aboveground. We hypothesized that PHPP application leads to specific plant-mediated responses in the rhizosphere microbiota. We applied different PHPPs on greenhouse-grown apple and strawberry plants, cultivated in different soils. The effects of aboveground PHPP applications on the root-associated microbiota were analyzed by 16S rRNA gene amplicon sequencing. No consistent effects were observed across three experimental trials, although alpha diversity tended to be decreased after PHPP application. In some cases, shifts in community composition (PERMANOVA R2 = 0.192, P = 0.001) or increases in dispersion (PERMDISP Padj = 0.040) became evident. Movento treatments caused, in part, deterministic shifts in community assembly, whereas Serenade ASO treatments caused rather stochastic shifts. Effects were concluded to be probably transient and to disappear without continuous product application. These rather heterogenous temporary responses are in line with the concept of the “Anna Karenina principle,” under which terms PHPP applications can act as mild stress factors and slightly and transiently alter the belowground bacterial community. These findings indicate that aboveground PHPP applications can have product-specific implications for the root-associated microbiome, which should be considered in the context of microbiome management strategies. [Formula: see text] Copyright © 2025 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Lipomatous hypertrophy of the interatrial septum
Authors: Rullo Christine 
Published: August 2024

ABSTRACT
Lipomatous hypertrophy of the interatrial septum (LHIS) is a rare but benign cardiac tumor that can be found on cardiac imaging such as echocardiogram, or during surgery or an autopsy. Cardiac MRI is the best imaging modality to determine the borders of the tumor and its extension into the intraventricular septum and ventricular free wall. Patients require close monitoring because LHIS may cause right or left outflow tract obstruction or superior vena cava obstruction, requiring cardiac surgical intervention. This article describes a patient with LHIS who underwent cardiac surgery because of her increasing symptomatology.
Training and Sustaining: Training and Learning Collaborative Outcomes Across a Statewide Network for Early Autism Diagnosis
Authors: McNally Keehn Rebecca , Paxton Angela , Delaney Mary , Ciccarelli Mary 
Published: August 2024

Abstract:

Objective:
The objective of this study was to describe the development of a primary care professional (PCP) autism diagnosis training model and to report on outcomes related to PCP training and sustained engagement in a longitudinal learning collaborative.

Methods:
We developed Accelerating the Diagnosis of Autism with Primary care Training (ADAPT), a training program to prepare PCPs to develop independent competency in evaluation of autism in children aged 14 to 48 months. ADAPT includes didactic and case-based modules and practice-based coaching delivered by an expert diagnostic specialist; after training, PCPs participate in a longitudinal learning collaborative. Aligned with competency-based medical education standards, measures of autism evaluation knowledge and diagnostic competency are collected.

Results:
From 2021 to 2023, 13 PCPs completed ADAPT didactic and practicum training to reach competency in independent autism evaluation. Clinicians demonstrated significant improvement in total autism knowledge after didactic training (p = 0.02). Scoring agreement on an autism observational assessment tool between clinicians and expert diagnosticians improved over case observations and practicum evaluations. Similarly, PCPs demonstrated improved evaluation competence, moving on average from Advanced Beginner to Competent Performer as rated by expert diagnosticians. After training, PCPs attended 57% of monthly learning collaborative sessions.

Conclusion:
Training PCPs to deliver autism evaluations for young children as part of tiered community-based models of care is a promising solution to address access and waitlist challenges. ADAPT is an intensive, standardized PCP training model that results in achievement of independent competency and sustained engagement in autism evaluation. Effectiveness-implementation studies are needed to ensure scalability and sustainability of training models.
The level of glucose in pancreatic cyst fluid is more accurate than carcinoembryonic antigen to identify mucinous tumors: A French multicenter study
Authors: Williet Nicolas , Caillol Fabrice , Karsenti David , Abou-Ali Einas , Camus Marine , Belle Arthur , Chaput Ulriikka , Levy Jonathan , Ratone Jean-Philippe , Tournier Quentin , Grange Rémi , Le Roy Bertrand , Becq Aymeric , Phelip Jean-Marc 
Published: August 2024

ABSTRACT

Background and Objectives
Pancreatic cyst fluid level of glucose is a promising marker to identify mucinous from nonmucinous tumors, but the glucose assay has not yet been recommended. The objective of this study is to compare the diagnostic performances of pancreatic cyst fluid level of glucose and carcinoembryonic antigen (CEA).

Methods
In this French multicenter study, data of consecutive patients who underwent fine-needle aspiration of pancreatic cyst with intracyst glucose assay between 2018 and 2022 were retrospectively reviewed. The area under the receiver operating characteristic curve (AUROC) of glucose and corresponding sensitivity (Se), specificity (Sp), accuracy (Acc), positive predictive value (PPV), and negative predictive value (NPV) were calculated and compared with those of CEA. The best threshold of glucose was identified using the Youden index.

Results
Of the 121 patients identified, 81 had a definitive diagnosis (46 mucinous, 35 nonmucinous tumors) and were included for analysis. An intracystic glucose level <41.8 mg/dL allowed identification of mucinous tumors with better diagnostic performances (AUROC, 93.6%; 95% confidence interval, 87.2%–100%; Se, 95.3%; Sp, 91.2%; Acc, 93.5%; PPV, 93.2%; NPV, 93.9%) compared with CEA level >192 ng/mL (AUROC, 81.2%; 95% confidence interval, 71.3%–91.1%; Se, 41.7%; Sp, 96.9%; Acc, 67.6%; PPV, 93.8%; NPV, 59.6%) (P = 0.035). Combining values of glucose and CEA did not offer additional benefit in terms of diagnosis.

Conclusion
Our results confirm previously published data and support the use of pancreatic cyst fluid glucose for the identification of mucinous tumors when the definitive diagnosis remains uncertain.
Female and male factors that impact on frequency of sexual intercourse in aging couples: a cross-sectional study
Authors: Pio Janaina , Valadares Ana Lucia , Costa Paiva Lúcia 
Published: August 2024

Abstract

Objectives
To assess the prevalence and factors associated with dyspareunia and the lack of sexual intercourse in women between 50 and 70 years cohabiting with their partners.

Methods
This is a descriptive and exploratory cross-sectional study using the snowball technique with prospective data collection using a structured questionnaire to describe multiple aspects of health and sexuality among 266 cohabiting Brazilian couples aged 50 to 70.

Results
The prevalence of lack of sexual activity was 20%. Factors associated with sexual inactivity were female sexual dysfunction (OR: 9.87, 95% CI: 3.24‐30.10, P < 0.001), female dissatisfaction with the partner as a lover (OR: 5.86, 95% CI: 2.03‐16.88, P = 0.001), male sexual dysfunction (OR: 4.51, 95% CI: 1.60‐12.70, P = 0.004), and poor self-rated male health (OR: 3.66, 95% CI: 1.29‐10.40, P = 0.015). The prevalence of dyspareunia was 42.3% in the sample of sexually active women. Factors associated with dyspareunia were female sexual dysfunction (OR: 2.7, 95%, CI: 1.26‐5.77, P = 0.010), moderate/severe vaginal dryness (OR: 4.67, 95% CI: 2.21‐9.87, P < 0.001), and vaginal discomfort (OR: 4.03, 95% CI: 1.77‐9.17, P < 0.001).

Conclusions
The results showed that male, female, and dyadic factors were associated with a lack of sexual activity. On the other hand, only female factors were associated with dyspareunia among sexually active couples.
Human-induced pluripotent stem cell–based hepatic modeling of lipid metabolism–associated TM6SF2-E167K variant
Authors: Faccioli Lanuza A.P. , Sun Yiyue , Animasahun Olamide , Motomura Takashi , Liu Zhenghao , Kurihara Takeshi , Hu Zhiping , Yang Bo , Cetin Zeliha , Baratta Annalisa M. , Shankaran Ajay , Nenwani Minal , Altay Leyla Nurcihan , Huang Linqi , Meurs Noah , Franks Jonathan , Stolz Donna , Gavlock Dillon C. , Miedel Mark T. , Ostrowska Alina , Florentino Rodrigo M. , Fox Ira J. , Nagrath Deepak , Soto-Gutierrez Alejandro 
Published: August 2024

Background and Aims:
TM6SF2 rs58542926 (E167K) is related to an increased prevalence of metabolic dysfunction–associated steatotic liver disease. Conflicting mouse study results highlight the need for a human model to understand this mutation’s impact. This study aims to create and characterize a reliable human in vitro model to mimic the effects of the TM6SF2-E167K mutation for future studies.

Approach and Results:
We used gene editing on human-induced pluripotent stem cells from a healthy individual to create cells with the TM6SF2-E167K mutation. After hepatocyte-directed differentiation, we observed decreased TM6SF2 protein expression, increased intracellular lipid droplets, and total cholesterol, in addition to reduced VLDL secretion. Transcriptomics revealed the upregulation of genes involved in lipid, fatty acid, and cholesterol transport, flux, and oxidation. Global lipidomics showed increased lipid classes associated with endoplasmic reticulum (ER) stress, mitochondrial dysfunction, apoptosis, and lipid metabolism. In addition, the TM6SF2-E167K mutation conferred a proinflammatory phenotype with signs of mitochondria and ER stress. Importantly, by facilitating protein folding within the ER of hepatocytes carrying TM6SF2-E167K mutation, VLDL secretion and ER stress markers improved.

Conclusions:
Our findings indicate that induced hepatocytes generated from human-induced pluripotent stem cells carrying the TM6SF2-E167K recapitulate the effects observed in human hepatocytes from individuals with the TM6SF2 mutation. This study characterizes an in vitro model that can be used as a platform to identify potential clinical targets and highlights the therapeutic potential of targeting protein misfolding to alleviate ER stress and mitigate the detrimental effects of the TM6SF2-E167K mutation on hepatic lipid metabolism.
Long-term Visual Acuity Outcomes of Deep Sclerectomy in Pediatric Glaucoma
Authors: Alkhalifah Muhannad I. , Mousa Ahmed , Al Obeidan Saleh A. 
Published: August 2024

Précis:
This study provides evidence of the long-term efficacy and safety of deep sclerectomy as a successful surgical intervention option in cases with childhood glaucoma.

Objectives:
The primary objective was to evaluate the long-term visual acuity outcomes of deep sclerectomy in pediatric glaucoma and identify factors predicting poor prognosis. The secondary objective was to evaluate the long-term success rate of deep sclerectomy in controlling intraocular pressure (IOP).

Methods:
A retrospective review was conducted of all pediatric patients who underwent deep sclerectomy at King Abdulaziz University Hospital (KAUH) between 2001 and 2016. We included all patients who had valid visual acuity tests. The preoperative findings and long-term visual and IOP outcomes were analyzed.

Results:
A total of 83 eyes of 68 patients were included. The mean (SD) age of participants was 11.1 (4.0) years (range: 5–25 y). The mean age at surgery was 5.9 months, and the mean follow-up period was 10.75 years. The majority of cases (83.1%) were primary congenital glaucoma. Visual acuity was ≥20/40 in 56.6% of cases, ranged between 20/40 and 20/200 in 18.1%, and was ≤20/200 in 25.3% of the operated eyes. Complete success rate (IOP ≤21 mm Hg without medications) after one surgery was achieved in 53 eyes (63.86%). Qualified success rate (IOP ≤21 mm Hg with medications) was achieved in 8 eyes (9.6%), while 22 eyes (26.5%) failed to achieve the target IOP of ≤21 mm Hg or needed additional surgery to achieve it. Nine eyes (10.74%) had postoperative complications.

Conclusion:
Deep sclerectomy is a reasonable option for pediatric glaucoma that can provide good long-term visual outcomes and IOP control with a lower risk of surgical complications.
Caregiving Ability of Mothers of Children With Cancer: Qualitative Content Analysis
Authors: Abbasnezhad Masoomeh , Rassouli Maryam , Nasrabadi Tahereh , Nasrollah Sepideh 
Published: August 2024

Background
Childhood cancer confronts the child and the parents with considerable degrees of stress. Because caring for the child is mainly the role of the mother in most families, her ability to take care of the affected child is very important.

Objective
To explore the caregiving ability of Iranian mothers who have children diagnosed with cancer.

Methods
In this present study, which was conducted using the Directed Qualitative Content Analysis Method, 11 parents having children diagnosed with cancer and 5 professional caregivers working at the Department of Hematology and Oncology of Mofid Children Hospital in Tehran, Iran, were selected using purposeful sampling method. Data were collected through semistructured interviews. Data analysis was performed simultaneously with data collection using the Directed Content Analysis Approach.

Results
Five main categories emerged, namely, care exhaustion, care confusion, spiritual conflict, care competence, and care preparedness that represent the beneficiaries’ perception of the caring ability of Iranian mothers of cancer-afflicted children.

Conclusion
Study results revealed that the caregiving capacity of mothers nurturing cancer-stricken children can be evaluated across 5 domains, encompassing a spectrum of maternal requirements in child care. Improving these domains can elevate maternal caregiving proficiency, fostering self-care and enhancing care for the ailing child.

Implication for Practice
A program can be developed based on the findings of the present study, in order to improve the caring ability of mothers of cancer-afflicted children, which results in improving the mother’s care for her cancer-afflicted child.
Comparison of the BIG Score and Pediatric Trauma Score for Predicting Mortality
Authors: Az Adem , Dogan Yunus , Sogut Ozgur , Akdemir Tarik 
Published: August 2024

Objectives
The BIG score (base deficit + [2.5 × international normalized ratio] + [15 – Glasgow Coma Score]) was compared with the Pediatric Trauma Score (PTS) for predicting mortality in pediatric patients with multiple trauma.

Methods
This retrospective, single-center study included 318 consecutive pediatric patients (aged 1–18 years) with multiple trauma who were admitted to the emergency department between January 1, 2021, and December 31, 2023. The demographic characteristics, clinical characteristics, and trauma scores (BIG score and PTS) were compared between survivors and nonsurvivors to identify factors associated with mortality.

Results

A PTS of 7 had 100% sensitivity and 81.03% specificity for predicting mortality, with an area under the curve of 0.97 (95% confidence interval 0.9–0.99). Although the positive predictive value (PPV) was low (33.7%), the negative predictive value (NPV) was 100%. A BIG score of 13.7 was identified as the cutoff for mortality, with 92.86% sensitivity and 95.52% specificity (area under the curve 0.98, 95% confidence interval 0.96–0.99). The PPV was 66.7% and the NPV was 99.3%.

Conclusions
Both the PTS and the BIG score were strong predictors of mortality in pediatric patients with multiple trauma. The BIG score had a higher specificity and PPV, whereas a PTS of 7 had 100% sensitivity and a higher NPV.