bluuebunny/crossref_metadata_2025_split huggingface dataset:
Out-of-pocket expenses reported by families of children with medical complexity
Authors: Belza Christina , Cohen Eyal , Orkin Julia , Fayed Nora , Major Nathalie , Quartarone Samantha , Moretti Myla 
Published: July 2023

Abstract

Objectives
Due to their medical and technology dependence, families of children with medical complexity (CMC) have significant costs associated with care. Financial impact on families in general have been described, but detailed exploration of expenses in specific categories has not been systematically explored. Our objective was to describe out-of-pocket (OOP) expenses incurred by caregivers of CMC and to determine factors associated with increased expenditures.

Methods
This is a secondary observational analysis of data primary caregiver-reported OOP expenses as part of a randomized control trial conducted in Ontario, Canada. Caregivers completed questionnaires reporting OOP costs. Descriptive statistics were utilized to report OOP expenses and a linear regression model was conducted.

Results
107 primary caregivers of CMC were included. The median (IQR) age of participants was 34.5 years (30.5 to 40.5) and 83.2% identified as the mother. The majority were married or common-law (86.9%) and 50.5% were employed. The participant’s children [median (IQR) age 4.5 (2.2 to 9.7); 57.9% male] most commonly had a neurological/neuromuscular primary diagnosis (46.1%) and 88% utilized medical technology. Total OOP expenses were $8,639 CDN annually (IQR = $4,661 to $31,326) with substantial expenses related to childcare/homemaking, travel to appointments, hospitalizations, and device costs. No factors associated with greater likelihood of OOP expenses were identified. A P-value of &lt;0.05 was considered significant.

Conclusion
Caregivers of CMC incur significant OOP expenses related to the care of their children resulting in financial burden. Future exploration of the financial impact on caregiver productivity, employment, and identification of resources to mitigate OOP expenses will be important for this patient population.
Radiation injury and gut microbiota-based treatment
Authors: Wang Weihong , Cui Bota , Nie Yongzhan , Sun Lijuan , Zhang Faming 
Published: July 2023

Abstract
The exposure to either medical sources or accidental radiation can cause varying degrees of radiation injury (RI). RI is a common disease involving multiple human body parts and organs, yet effective treatments are currently limited. Accumulating evidence suggests gut microbiota are closely associated with the development and prevention of various RI. This article summarizes 10 common types of RI and their possible mechanisms. It also highlights the changes and potential microbiota-based treatments for RI, including probiotics, metabolites, and microbiota transplantation. Additionally, a 5P-Framework is proposed to provide a comprehensive strategy for managing RI.
Microvascular arterial disease of the brain and the heart: a shared pathogenesis
Authors: Bradley C P , Berry C 
Published: July 2023

Summary
Microvascular arterial disease in the heart manifest as coronary microvascular dysfunction. This condition causes microvascular angina and is associated increased morbidity and mortality. Microvascular arterial disease in the brain is referred to as cerebrovascular small vessel disease. This is responsible for 45% of dementias and 25% of ischaemic strokes. The heart and brain share similar vascular anatomy and common pathogenic risk factors are associated with the development of both coronary microvascular dysfunction and cerebrovascular small vessel disease. Microvascular disease in the heart and brain also appear to share common multisystem pathophysiological mechanisms. Further studies on diagnostic approaches, epidemiology and development of disease-modifying therapy seem warranted.
Frailty in younger adults in hospital
Authors: Gordon E H , Peel N M , Hubbard R E , Reid N 
Published: July 2023

Summary

Background
Even though frailty has been extensively measured in the acute care setting, relatively little is known about the frailty of younger adult inpatients.

Aim
This study aimed to measure frailty in a sample of hospitalized adults aged 18 years and over and to examine how frailty in younger adult inpatients differs from middle-aged and older adult inpatients.

Design
Secondary analyses of prospectively collected cohort data.

Methods
Research nurses assessed 910 patients at admission to four Australian hospitals using the interRAI Acute Care instrument. Comparison of frailty index (FI) scores and domains was conducted across three age groups: younger (18–49 years), middle-aged (50–69 years) and older adults (≥70 years). Multivariable logistic regression examined risk of prolonged length of stay and unfavourable discharge destination.

Results
Younger adults (n = 214; 23.5%) had a mean (SD) FI of 0.19 (0.10). Approximately 27% (n = 57) of younger adults were frail (FI &gt; 0.25). Mood and behaviour, health symptoms and syndromes, nutrition and pain were the most frequently affected domains in younger adults and 50% had ≥3 comorbidities. Frailty increased the risk of long length of stay (odds ratio (OR) = 1.77, P &lt; 0.001) but not the risk of an unfavourable discharge (OR = 1.40, P = 0.20) in younger adults.

Conclusions
This study showed that frailty is prevalent in younger patients admitted to acute care and is associated with adverse outcomes. This study was a critical first step towards establishing an understanding of frailty in younger hospitalized adults.
The Non-Dereliction in Evolution: Trophic Specialisation Drives Convergence in the Radiation of Red Devil Spiders (Araneae: Dysderidae) in the Canary Islands
Authors: Bellvert Adrià , Adrián-Serrano Silvia , Macías-Hernández Nuria , Toft Søren , Kaliontzopoulou Antigoni , Arnedo Miquel A 
Published: July 2023

Abstract
Natural selection plays a key role in deterministic evolution, as clearly illustrated by the multiple cases of repeated evolution of ecomorphological characters observed in adaptive radiations. Unlike most spiders, Dysdera species display a high variability of cheliceral morphologies, which has been suggested to reflect different levels of specialization to feed on isopods. In this study, we integrate geometric morphometrics and experimental trials with a fully resolved phylogeny of the highly diverse endemic species from the Canary Islands to 1) quantitatively delimit the different cheliceral morphotypes present in the archipelago, 2) test their association with trophic specialization, as reported for continental species, 3) reconstruct the evolution of these ecomorphs throughout the diversification of the group, 4) test the hypothesis of convergent evolution of the different morphotypes, and 5) examine whether specialization constitutes a case of evolutionary irreversibility in this group. We show the existence of 9 cheliceral morphotypes and uncovered their significance for trophic ecology. Further, we demonstrate that similar ecomorphs evolved multiple times in the archipelago, providing a novel study system to explain how convergent evolution and irreversibility due to specialization may be combined to shape phenotypic diversification in adaptive radiations.
Effect of progesterone infused controlled internal drug releasing (CIDR) device and timing of gonadotropin stimulation using P.G. 600 on reproductive success in ewes bred out of season
Authors: Redden Reid R , Neville Tammi L , Black Danielle N , Crosswhite Mellissa R , Dahlen Crosswhite Carl R 
Published: July 2023

Abstract
Objectives of this study were to determine effects of exogenous progesterone (via controlled internal drug releasing devices; CIDR) in combination with exogenous gonadotropins (PMSG/hCG) use either at CIDR removal or 1 d before CIDR removal to induce estrus and cyclicity and subsequently enhance the proportion of ewes lambing, lambing rate, prolificacy, and days to lambing in ewes bred out of season. Multiparous ewes (n = 414) were randomly assigned to one of four treatments: untreated (U, n = 122), 7 d CIDR (C, n = 97), 7 d CIDR plus P.G. 600 (240 IU pregnant mare serum gonadotropin [PMSG] and 120 IU human chorionic gonadotropin [hCG]) at CIDR removal (CPG0, n = 97), and 7 d CIDR plus P.G. 600 (240 IU PMSG and 120 IU hCG) 1 d before CIDR removal (CPG-1, n = 98). Rams (n = 15) were joined with ewes immediately after CIDR removal and remained with ewes for a 21 d breeding period. Lambing data were summarized for the first 10 days of the lambing season and overall. Categorical data were analyzed using the GLIMMIX procedure of SAS whereas non-categorical data were analyzed using the mixed procedure. Proportion of ewes lambing in the first 10 d was greater (P &lt; 0.05) for CPG0 and CPG-1 ewes compared with C ewes, which was greater (P &lt; 0.0001) compared with U ewes. Overall proportion of ewes lambing was greater (P ≤ 0.0001) in all treatments utilizing CIDR compared with U ewes, but no differences (P ≥ 0.84) due to P.G. 600 were detected compared with C. Lambing rate in the first 10 d was greater (P &lt; 0.05) for CPG-1 than C, with CPGO being intermediate, and all CIDR-treated ewes being greater than U (P &lt; 0.0001). Overall lambing rate increased (P ≤ 0.0001) in all treatments utilizing CIDR compared with U ewes, but no differences (P ≥ 0.76) due to P.G. 600 were detected compared with C. Prolificacy was similar among all treatments both for the first 10 d of the lambing season (P = 0.86) and overall (P = 0.80). Day of lambing in the lambing season was reduced (P ≤ 0.03) for CPG0 and CPG-1 compared with CIDR-treated ewes, which was reduced (P &lt; 0.0001) compared with U ewes (days 10.6, 9.0, 13.4, and 24.4 ± 0.9 for CPG0, CPG-1, CON, and U, respectively). Though timing of P.G. 600 did not influence results, the combination of CIDR and P.G. 600 enhanced the proportion of lambs born earlier in the lambing season, and incorporating a CIDR with or without P.G. 600 enhanced the overall proportion of ewes lambing and lambing rate in out-of-season breeding scenarios.
Tardigrade proteins: molecular tools in the phenomenon of anhydrobiosis
Authors: Krakowiak Michalina , Bartylak Tomasz , Kmita Hanna , Kaczmarek Łukasz , Nawrot Robert 
Published: July 2023

Abstract
Tardigrada (water bears) are a group of small invertebrates known for their ability to survive extreme desiccation by entering an anhydrobiotic state. This state is characterized by the loss of ≤ 98% of body water, resulting in body shrinkage and almost complete cessation of metabolism. In anhydrobiosis, multiple mechanical and biochemical stress effects, such as protein denaturation and aggregation, DNA damage, formation of reactive oxygen species, membrane disintegration and degeneration of cellular compartments, are counteracted by various proteins. Although multiple studies of individual proteins and tardigrade proteomes have been conducted, our knowledge of tardigrade anhydrobiosis-related proteins has not yet been reviewed. To fill this gap, based on available papers, we present a review of all tardigrade proteins known to contribute to desiccation survival, including intrinsically disordered proteins, heat shock proteins and reactive oxygen species-scavenging enzymes. Although proteins are the major anhydrobiosis-related factors in tardigrades, many questions regarding the role of the tardigrade proteome in anhydrobiosis remain unanswered.
Clinical characteristics of hypersensitivity pneumonitis: non-fibrotic and fibrotic subtypes
Authors: Chen Xueying , Yang Xiaoyan , Ren Yanhong , Xie Bingbing , Xie Sheng , Zhao Ling , Wang Shiyao , Geng Jing , Jiang Dingyuan , Luo Sa , He Jiarui , Shu Shi , Hu Yinan , Zhu Lili , Li Zhen , Zhang Xinran , Liu Min , Dai Huaping 
Published: July 2023

Abstract

Background:
The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis (HP) guidelines. The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis (NFHP) and fibrotic hypersensitivity pneumonitis (FHP) and explore factors associated with the presence of fibrosis.

Methods:
In this prospective cohort study, patients diagnosed with HP through a multidisciplinary discussion were enrolled. Collected data included demographic and clinical characteristics, laboratory findings, and radiologic and histopathological features. Logistic regression analyses were performed to explore factors related to the presence of fibrosis.

Results:
A total of 202 patients with HP were enrolled, including 87 (43.1%) NFHP patients and 115 (56.9%) FHP patients. Patients with FHP were older and more frequently presented with dyspnea, crackles, and digital clubbing than patients with NFHP. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 153, gastrin-releasing peptide precursor, squamous cell carcinoma antigen, and antigen cytokeratin 21-1, and count of bronchoalveolar lavage (BAL) eosinophils were higher in the FHP group than in the NFHP group. BAL lymphocytosis was present in both groups, but less pronounced in the FHP group. Multivariate regression analyses revealed that older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors for the development of FHP. Twelve patients developed adverse outcomes, with a median survival time of 12.5 months, all of whom had FHP.

Conclusions:
Older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors associated with the development of FHP. Prognosis of patients with NFHP was better than that of patients with FHP. These results may provide insights into the mechanisms of fibrosis in HP.
Professionalism in Physician Assistant Education as a Predictor of Future Licensing Board Disciplinary Actions
Authors: Barry Carey L. , Coombs Jennifer , Buchs Shalon , Kim Sooji , Grant Travis , Henry Trenton , Parente Jason , Spackman Jared 
Published: July 2023

Purpose
The purpose of this study was to evaluate associations between postgraduate disciplinary actions (PGDA) by state licensing boards and physician assistant (PA) school documented professionalism violations (DPV) and academic probation.

Methods
This was a retrospective cohort study comprising PA graduates from 2001 to 2011 at 3 institutions (n = 1364) who were evaluated for the main outcome of PGDA and independent variable of DPV and academic probation. Random-effects multiple logistic regression and accelerated failure time parametric survival analysis were used to investigate the association of PGDA with DPV and academic probation.

Results
Postgraduate disciplinary action was statistically significant and positively associated with DPV when unadjusted (odds ratio [OR] = 5.15; 95% CI: 1.62–16.31; P = .01) and when adjusting for age, sex, overall PA program GPA (GPA), and Physician Assistant National Certifying Exam Score (OR = 5.39; 95% CI: 1.54–18.85; P = .01) (fully adjusted). Academic probation increased odds to 8.43 times (95% CI: 2.85–24.92; P < .001) and 9.52 times (95% CI: 2.38–38.01; P < .001) when fully adjusted.

Conclusion
Students with professionalism violation or academic probation while in the PA school had significant higher odds of receiving licensing board disciplinary action compared with those who did not. Academic probation had a greater magnitude of effect and could represent an intersection of professionalism and academic performance.
Implicit Association Test Alone Is Not Sufficient to Increase Underrepresented Minority Representation in Physician Assistant Programs
Authors: Ryujin Darin , Dalton Doris , Yole-Lobe Menerva , DiBiase Michelle , Phelps Paula , Madden Ann , Clark Jon , Barry Carey L. , Rodriguez José E. , Honda Trenton 
Published: July 2023

Purpose
Physician assistant (PA) program matriculants are consistently less diverse than the US population. This study evaluates whether administration of an Implicit Association Test (IAT) to PA program admission committees is associated with changes in the likelihood of (1) receiving an admission interview, (2) receiving an offer of admission, and (3) matriculation of individuals underrepresented in medicine (URiM).

Methods
Admission committees from 4 PA programs participated in an IAT before the 2019/2020 admissions cycle. Applicant outcome data (n = 5796) were compared with 2018/2019 cycle (n = 6346). Likelihood of URiM students receiving offers to interview, offers of admission, and matriculation were evaluated using random effects multiple logistic regression models. Fully adjusted random effects models included URiM status, year (control vs. intervention), multiplicative interaction terms between URiM and year, applicant age, and undergraduate grade point average (GPA) Secondary analyses examined associations of each race/ethnicity individually.

Results
Underrepresented in medicine status, age, and GPA were significantly associated with all admission outcomes (P < .05). The intervention effect was not statistically significant. In sensitivity analyses examining each individual race rather than URiM status, our results did not importantly differ.

Conclusion
Findings suggest admission committee member participation in IAT before admissions had no significant impact on the likelihood of admission of URiM students. This may suggest that making individuals aware of their implicit biases is not, in and of itself, sufficient to meaningfully affect the diversity of PA program admission metrics.
Young-onset Rectal Cancer
Authors: White Michael G. , Damania Ashish , Alshenaifi Jumanah , Sahasrabhojane Pranoti , Peacock Oliver , Losh Jillian , Wong Matthew C. , Lutter-Berkova Zuzana , Chang George J. , Futreal Andrew , Wargo Jennifer A. , Ajami Nadim J. , Kopetz Scott , You Y. Nancy 
Published: July 2023

Objective:
External exposures, the host, and the microbiome interact in oncology. We aimed to investigate tumoral microbiomes in young-onset rectal cancers (YORCs) for profiles potentially correlative with disease etiology and biology.

Background:
YORC is rapidly increasing, with 1 in 4 new rectal cancer cases occurring under the age of 50 years. Its etiology is unknown.

Methods:
YORC (<50 y old) or later-onset rectal cancer (LORC, ≥50 y old) patients underwent pretreatment biopsied of tumor and tumor-adjacent normal (TAN) tissue. After whole genome sequencing, metagenomic analysis quantified microbial communities comparing tumors versus TANs and YORCs versus LORCs, controlling for multiple testing. Response to neoadjuvant therapy (NT) was categorized as major pathological response (MPR, ≤10% residual viable tumor) versus non-MPR.

Results:
Our 107 tumors, 75 TANs from 37 (35%) YORCs, and 70 (65%) LORCs recapitulated bacterial species were previously associated with colorectal cancers (all P<0.0001). YORC and LORC tumoral microbiome signatures were distinct. After NT, 13 patients (12.4%) achieved complete pathologic response, whereas MPR occurred in 47 patients (44%). Among YORCs, MPR was associated with Fusobacterium nucleaum, Bacteroides dorei, and Ruminococcus bromii (all P<0.001), but MPR in LORC was associated with R. bromii (P<0.001). Network analysis of non-MPR tumors demonstrated a preponderance of oral bacteria not observed in MPR tumors.

Conclusions:
Microbial signatures were distinct between YORC and LORC. Failure to achieve an MPR was associated with oral bacteria in tumors. These findings urge further studies to decipher correlative versus mechanistic associations but suggest a potential for microbial modulation to augment current treatments.
A Combination of Machine Learning and PBPK Modeling Approach for Pharmacokinetics Prediction of Small Molecules in Humans
Authors: Li Yuelin , Wang Zonghu , Li Yuru , Du Jiewen , Gao Xiangrui , Li Yuanpeng , Lai Lipeng 
Published: July 2023

AbstractRecently, there has been rapid development in model-induced drug development, which has the potential to reduce animal experiments and accelerate drug discovery. Physiologically based pharmacokinetic (PBPK) and machine learning (ML) models are commonly used in early drug discovery to predict drug properties. However, basic PBPK models require a large number of molecule-specific inputs from in vitro experiments, which hinders the efficiency and accuracy of these models. To address this issue, this paper introduces a new computational platform that combines ML and PBPK models. The platform predicts molecule PK profiles with high accuracy and without the need for experimental data.This study developed a whole-body PBPK model and ML models of plasma protein unbinding (fup), Caco-2 cell permeability, and total plasma clearance to predict the PK of small molecules. Pharmacokinetic profiles were simulated using a “bottom-up” PBPK modeling approach with ML inputs. Additionally, 40 compounds were used to evaluate the platform’s accuracy. Results showed that the ML-PBPK model predicted the area under the concentration-time curve (AUC) with 62.5% accuracy within a 2-fold range, which was higher than using in vitro inputs with 47.5% accuracy.The ML-PBPK model platform provides high accuracy in prediction and reduces the number of experiments and time required compared to traditional PBPK approaches. The platform successfully predicts human PK parameters without in vitro and in vivo experiments and can potentially guide early drug discovery and development.
A host AAA-ATPase exhibits bacteriolytic activity for clearance of microbial infection
Authors: Ghosh Sourav , Roy Suvapriya , Baid Navin , Das Udit Kumar , Rakshit Sumit , Sanghavi Paulomi , Hajra Dipasree , Menon Sneha , Sahil Mohammad , Shaw Sudipti , Rajmani Raju S , Adicherla Harikrishna , Mondal Jagannath , Chakravortty Dipshikha , Mallik Roop , Banerjee Anirban 
Published: July 2023

AbstractAn array of host cytosol guarding factors impede bacterial proliferation and preserve cellular sterility. Amongst them, proteasomal degradation of ubiquitinated pathogens has emerged as a critical mechanism for ensuring cytosolic sanctity. We wondered how proteasomes, with their small size and inability to extract membrane-bound proteins, can eradicate pathogens. Here, we unveil a unique strategy, wherein VCP/p97, a host AAA-ATPase, eliminates pathogens by exerting mechanical force that physically unfolds and pulls out ubiquitinated proteins from bacterial membrane. Combining a single-molecule approach along with molecular dynamic simulation andin-vitroreconstitution, we demonstrate that protein extraction by p97 causes extensive membrane lysis and release of cytosolic contents from phylogenetically diverse microbes. Additionally, in anin-vivomouse sepsis model, this segregase-dependent bactericidal effect of p97 abrogated microbial proliferation in host tissues. Overall, we discovered a distinct innate antimicrobial function of p97, that protects the host against lethal bacterial infections.One Sentence SummaryA host AAA-ATPase exhibits bacteriolytic activity.