bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequence-developability mapping of affibody and fibronectin paratopes via library-scale variant characterization
Authors: Nielsen Gregory H , Schmitz Zachary D , Hackel Benjamin J 
Published: June 2024

Abstract
Protein developability is requisite for use in therapeutic, diagnostic, or industrial applications. Many developability assays are low throughput, which limits their utility to the later stages of protein discovery and evolution. Recent approaches enable experimental or computational assessment of many more variants, yet the breadth of applicability across protein families and developability metrics is uncertain. Here, three library-scale assays—on-yeast protease, split green fluorescent protein (GFP), and non-specific binding—were evaluated for their ability to predict two key developability outcomes (thermal stability and recombinant expression) for the small protein scaffolds affibody and fibronectin. The assays’ predictive capabilities were assessed via both linear correlation and machine learning models trained on the library-scale assay data. The on-yeast protease assay is highly predictive of thermal stability for both scaffolds, and the split-GFP assay is informative of affibody thermal stability and expression. The library-scale data was used to map sequence-developability landscapes for affibody and fibronectin binding paratopes, which guides future design of variants and libraries.
RPA3-UMAD1 rs12702634 and rheumatoid arthritis–associated interstitial lung disease in European ancestry
Authors: Juge Pierre-Antoine , Sparks Jeffrey A , Gazal Steven , Ebstein Esther , Borie Raphaël , Debray Marie-Pierre , Kannengiesser Caroline , McDermott Gregory C , Cui Jing , Hayashi Keigo , Doyle Tracy J , van Moorsel Coline H M , van der Vis Joanne J , Grutters Jan C , Knevel Rachel , Heckert Sascha L , Vasarmidi Eirini , Antoniou Katerina M , van der Helm van Mil Annette H M , Boileau Catherine , Crestani Bruno , Dieudé Philippe 
Published: June 2024

Abstract

Objective
Recently, a genome-wide association study identified an association between RA-associated interstitial lung disease (ILD) and RPA3-UMAD1 rs12702634 in the Japanese population, especially for patients with a usual interstitial pneumonia (UIP) pattern. We aimed to replicate this association in a European population and test for interaction with MUC5B rs35705950.

Methods
In this genetic case–control association study, patients with RA and ILD and controls with RA and no ILD were included from France, the USA and the Netherlands. Only cases and controls from European genetic ancestries determined by principal components analysis were included in the analyses. RA was defined by the 1987 ACR or 2010 ACR/EULAR criteria and ILD by chest high-resolution CT scan, except in the control dataset from the Netherlands, where the absence of ILD was determined by chart review. Patients were genotyped for RPA3-UMAD1 rs12702634 and MUC5B rs35705950. Associations were tested using logistic regression adjusted for sex, age at RA onset, age at ILD onset or at certified absence of ILD, tobacco smoking status and country of origin.

Results
Among the 883 patients included, 322 were RA-ILD cases (36.5%). MUC5B rs35705950 was strongly associated with RA-ILD in all datasets {combined adjusted odds ratio [OR] 2.9 [95% CI 2.1, 3.9], P = 1.1 × 10−11. No association between RPA3-UMAD1 rs12702634 and RA-ILD was observed [combined OR 1.2 (95% CI 0.8, 1.6), P = 0.31. No interaction was found between RPA3-UMAD1 rs12702634 and MUC5B rs35705950 (P = 0.70).

Conclusion
Our findings did not support a contribution of RPA3-UMAD1 rs12702634 to the overall RA-ILD susceptibility in the European population.
Caught in the Act: Incipient Speciation at the Southern Limit of Viburnum in the Central Andes
Authors: Maya-Lastra Carlos A , Sweeney Patrick W , Eaton Deren A R , Torrez Vania , Maldonado Carla , Ore-Rengifo Malu I , Arakaki Mónica , Donoghue Michael J , Edwards Erika J 
Published: June 2024

Abstract
A fundamental objective of evolutionary biology is to understand the origin of independently evolving species. Phylogenetic studies of species radiations rarely are able to document ongoing speciation; instead, modes of speciation, entailing geographic separation and/or ecological differentiation, are posited retrospectively. The Oreinotinus clade of Viburnum has radiated recently from north to south through the cloud forests of Mexico and Central America to the Central Andes. Our analyses support a hypothesis of incipient speciation in Oreinotinus at the southern edge of its geographic range, from central Peru to northern Argentina. Although several species and infraspecific taxa have been recognized in this area, multiple lines of evidence and analytical approaches (including analyses of phylogenetic relationships, genetic structure, leaf morphology, and climatic envelopes) favor the recognition of just a single species, V. seemenii. We show that what has previously been recognized as V. seemenii f. minor has recently occupied the drier Tucuman-Bolivian forest region from Samaipata in Bolivia to Salta in northern Argentina. Plants in these populations form a well-supported clade with a distinctive genetic signature and they have evolved smaller, narrower leaves. We interpret this as the beginning of a within-species divergence process that has elsewhere in the neotropics resulted repeatedly in Viburnum species with a particular set of leaf ecomorphs. Specifically, the southern populations are in the process of evolving the small, glabrous, and entire leaf ecomorph that has evolved in four other montane areas of endemism. As predicted based on our studies of leaf ecomorphs in Chiapas, Mexico, these southern populations experience generally drier conditions, with large diurnal temperature fluctuations. In a central portion of the range of V. seemenii, characterized by wetter climatic conditions, we also document what may be the initial differentiation of the leaf ecomorph with larger, pubescent, and toothy leaves. The emergence of these ecomorphs thus appears to be driven by adaptation to subtly different climatic conditions in separate geographic regions, as opposed to parapatric differentiation along elevational gradients as suggested by Viburnum species distributions in other parts of the neotropics.
Influence of proportion of Brahman genetics on productivity of Brahman–Angus cows at weaning
Authors: Martins Thiago , Rocha Cecília Constantino , Driver Joseph Danny , Rae Owen , Elzo Mauricio Aguirre , Mateescu Raluca G , Santos José Eduardo Portela , Binelli Mario 
Published: June 2024

Abstract
This study evaluated the association between the proportion of Brahman genetics and productivity of Brahman–Angus cows at weaning using a 31-yr dataset containing 6,312 cows and 5,405 pregnancies. Cows were contemporaneously reared and enrolled in yearly breeding seasons under subtropical conditions of North-Central Florida. They were evenly distributed in six-breed groups (G) according to the proportion of Brahman genetics: G0% to 19%, G21% to 34%, G38% (Brangus), G41% to 59%, G63% to 78%, and G81% to 100%. The proportion of cows calving (84.9%) did not differ across the six-breed groups. However, cows in the G81% to 100% weaned fewer calves (90.8%) than cows in the G0% to 19% and G21% to 34% (95.7%, each). The weaning rate of cows in the G38% (94.3%), G41% to 59% (94.2%), and G63% to 78% (93.0%) was intermediate between these three breed groups. The preweaning calf mortality was greater for cows in the G81% to 100% (9.2%) than cows in the G0% to 19% and G21% to 34% (4.3%, each), but intermediate for cows in the G38% (5.7%), G41% to 59% (5.8%), and G63% to 78% (7.0%). Cows in the G81% to 100% also weaned lighter calves (220.6 kg) than cows in the G0% to 19% (245.2 kg), G21% to 34% (250.2 kg), G38% (247.9 kg), G41% to 59% (252.5 kg), and G63% to 78% (245.2 kg). Cows in the G0% to 19% weaned lighter calves than cows with 21% to 78% of Brahman genetics. The 205-d adjusted weaning weight evidenced the less productive results of cows in G0% to 19% and G81% to 100% compared with other genetic groups, as they calved at the fastest and slowest rate, respectively. Thus, the 205-d adjusted weaning weight eliminated this bias. Additionally, younger cows weaned lighter calves; and male calves were heavier at weaning than female calves. Both parity order of cow and calf sex altered the magnitude of the described association between breed group of cows and calf weaning weights. Overall, after adjusting for weaning rate and age of calves at weaning, the number of kilograms produced per cow submitted to reproduction was less for cows in the G0% to 19% (191.1 kg) and G81% to 100 (181.8 kg) compared with cows in the G21% to 34 (197.0 kg), G38 (195.9 kg), G41% to 59 (199.7), and G63% to 78 (196.2). Cows in the G81% to 100% were the least productive. Thus, a proportion of Brahman genetics between 21% and 78% ensured superior productivity of Brahman–Angus cows subjected to subtropical conditions.
Effects of developmental exposure to arsenic species on behavioral stress responses in larval zebrafish and implications for stress-related disorders
Authors: McAtee Demetrius , Abdelmoneim Ahmed 
Published: June 2024

Abstract
Arsenic (As) is globally detected in drinking water and food products at levels repeatedly surpassing regulatory thresholds. Several neurological and mental health risks linked to arsenic exposure are proposed; however, the nature of these effects and their association with the chemical forms of arsenic are not fully understood. Gaining a clear understanding of the etiologies and characteristics of these effects is crucial, particularly in association with developmental exposures where the nervous system is most vulnerable. In this study, we investigated the effects of early developmental exposure (6- to 120-h postfertilization [hpf]) of larval zebrafish to environmentally relevant concentrations of arsenic species—trivalent/pentavalent, inorganic/organic forms—on developmental, behavioral, and molecular endpoints to determine their effect on stress response and their potential association with stress-related disorders. At 120 hpf, the developing larvae were assessed for a battery of endpoints including survival, developmental malformities, background activity, and behavioral responses to acute visual and acoustic stimuli. Pooled larval samples were analyzed for alterations in the transcript levels of genes associated with developmental neurotoxicity and stress-related disorders. Developmental exposures at target concentrations did not significantly alter survival, overall development, or background activity, and had minor effects on developmental morphology. Sodium arsenate and monomethylarsonic acid exaggerated the behavioral responses of larval zebrafish, whereas sodium arsenite depressed them. Sodium arsenate induced significant effects on molecular biomarkers. This study highlights the effects of developmental exposure to arsenicals on the behavioral stress response, the role chemical formulation plays in exerting toxicological effects, and the possible association with stress-related disorders.
Incidence of complications among operative pediatric supracondylar humerus fractures using medial and lateral pins: a safe technique for percutaneous medial pin placement
Authors: Minifee Christopher D. , DeFilippo Christine G. , Carmichael Kelly D. 
Published: June 2024

Cross-pinning of displaced pediatric supracondylar elbow fractures offers a superior stability construct. However, there is a reluctance to use this construct by closed means because of the risk of iatrogenic ulnar nerve injuries associated with percutaneous medial pin placement. This study describes a safe technique for closed reduction percutaneous with medial pin placement. This study reviewed the clinical charts of 232 pediatric patients who underwent closed reduction with cross-pinning of Gartland type II and III supracondylar fractures from 2000 to 2022 at a single institution. All surgeries were performed by the same attending surgeon at the same institution, with the same technique of medial pin placement. The inpatient and outpatient notes were used to record patient demographic information, fracture classification, and postoperative complications. A total of 232 pediatric patients [114 boys, 118 girls; mean age: 5.8 (range: 1–14) years] with Gartland type II (n = 97) and III (n = 135) supracondylar fractures were included in the study. There were a total of seven (3.02%) postoperative complications: four (1.7%) ulnar neuropathies, two (0.86%) pin site infections, and one (0.43%) anterior interosseous nerve palsy. All documented postoperative complications were resolved by the 3-month follow-up visit. There were no complications of deep infection, malunion, or nonunion. With the proper technique, closed reduction with percutaneous medial pin fixation of pediatric supracondylar fractures is safe and produces excellent postoperative outcomes.
Level of Evidence: Level IV, case series.
Surgeon Recommendations for Physical Activity in Patients With Pediatric Hip Conditions
Authors: Li Jacqueline , Schaeffer Emily K. , Miller Stacey , Schreiber Verena M. , Hailer Yasmin D. , Clohisy John C. , Kim Harry K.W. , Mulpuri Kishore 
Published: June 2024

Background:
While physical activity (PA) is important during youth, it is unclear if children and adolescents with developmental dysplasia of the hip (DDH), Legg-Calvé-Perthes disease (LCPD), or slipped capital femoral epiphysis (SCFE) are expected or encouraged to return to PA once they have healed. This study examines the orthopaedic surgeons’ role in advising pediatric hip patients on the PA they should engage in, assessing their practice, opinions, and consensus when making recommendations.

Methods:
Orthopaedic surgeons were invited from member lists of 4 hip study groups. The survey included demographics, opinions regarding PA, and 10 case scenarios that queried respondents on the duration and intensity of PA as well as the restrictions on activity type that they would recommend for DDH, LCPD, or SCFE patients. Consensus was evaluated on a scale ranging from 0 to 1, with a value of 0 indicating no agreement among respondents and a value of 1 indicating complete agreement.

Results:
A total of 51 orthopaedic surgeons responded. While 94% agreed that it is important for school-aged hip patients to return to PA after they have healed, 53% believed that PA may compromise the hip and contribute to the development of osteoarthritis. Average standardized consensus was 0.92 for suggesting the patient engage in some amount of PA, 0.44 for suggesting the recommended daily minimum of 60 minutes of moderate-to-vigorous physical activity (MVPA), and 0.33 for suggesting restrictions on activity type. The most frequently selected restrictions included avoiding impact activities (93%, 235/254) and contact activities (58%, 147/254), followed by weight-bearing activities (24%, 62/254). Respondents were not aware of existing PA guidelines, although 57% expressed interest in following guidelines and 39% were uncertain.

Conclusions:
While there is consensus among orthopaedic surgeons that children with chronic hip conditions should engage in PA, there is considerable variation when recommending the recommended daily MVPA minimum and placing restrictions on activity type. This study suggests interest among orthopaedic surgeons in developing PA guidelines that optimize outcomes for pediatric hip patients.

Level of Evidence:
Level II—Survey study.
Intraoperative O-arm Use for Physeal Bar Excision
Authors: Richard Brian , Abbas Mohammed , Odeneye Oluwatobi , Türker Tolga 
Published: June 2024

Introduction:
Growth arrest caused by physeal bar formation in pediatric patients has posed a longstanding challenge in orthopedics. While growth arrest in pediatric distal radius fractures is relatively uncommon, its downstream consequences impact function, pain, and cosmesis. Physeal bar excision can be used to correct and prevent further growth arrest. The results of bar excision have been unreliable due to the difficulty of balancing complete bar resection while minimizing iatrogenic insult to the physis.

Materials and Methods:
In this article, we present a method utilizing intraoperative computed tomography O-arm for physeal bar excision.

Results:
A 10-year-old boy sustained an open distal radius fracture that was initially stabilized with plates and screws. Two of these screws were transphyseal and resulted in physeal bars and growth arrest. Due to age and the central location of his bars, bar excision was performed with the addition of intraoperative computed tomography. This resulted in a successful outcome with restoration of longitudinal growth of his distal radius.

Discussion:
This method offers improved localization of physeal bars intraoperatively and, subsequently, more precise bar excision while minimizing the risk of complications.
What Is the Potential Value of a Randomized Trial of Different Thresholds to Initiate Invasive Ventilation? A Health Economic Analysis
Authors: Yarnell Christopher J. , Barrett Kali , Heath Anna , Herridge Margaret , Fowler Robert A. , Sung Lillian , Naimark David M. , Tomlinson George 
Published: June 2024

OBJECTIVES:
To estimate the expected value of undertaking a future randomized controlled trial of thresholds used to initiate invasive ventilation compared with usual care in hypoxemic respiratory failure.

PERSPECTIVE:
Publicly funded healthcare payer.

SETTING:
Critical care units capable of providing invasive ventilation and unconstrained by resource limitations during usual (nonpandemic) practice.

METHODS:
We performed a model-based cost-utility estimation with individual-level simulation and value-of-information analysis focused on adults, admitted to critical care, receiving noninvasive oxygen. In the primary scenario, we compared hypothetical threshold A to usual care, where threshold A resulted in increased use of invasive ventilation and improved survival compared with usual care. In the secondary scenario, we compared hypothetical threshold B to usual care, where threshold B resulted in decreased use of invasive ventilation and similar survival compared with usual care. We assumed a willingness-to-pay of 100,000 Canadian dollars (CADs) per quality-adjusted life year.

RESULTS:
In the primary scenario, threshold A was cost-effective compared with usual care due to improved hospital survival (78.1% vs. 75.1%), despite more use of invasive ventilation (62% vs. 30%) and higher lifetime costs (86,900 vs. 75,500 CAD). In the secondary scenario, threshold B was cost-effective compared with usual care due to similar survival (74.5% vs. 74.6%) with less use of invasive ventilation (20.2% vs. 27.6%) and lower lifetime costs (71,700 vs. 74,700 CAD). Value-of-information analysis showed that the expected value to Canadian society over 10 years of a 400-person randomized trial comparing a threshold for invasive ventilation to usual care in hypoxemic respiratory failure was 1.35 billion CAD or more in both scenarios.

CONCLUSIONS:
It would be highly valuable to society to identify thresholds that, in comparison to usual care, either increase survival or reduce invasive ventilation without reducing survival.
Clinical and Histological Effects of Calcium Hydroxyapatite Filler in the Orofacial Region: A Study in Rats
Authors: Thums Marianna Ávila , Payeras Márcia Rodrigues , Cherubini Karen , Koth Valesca Sander , Salum Fernanda Gonçalves 
Published: June 2024

BACKGROUND
Calcium hydroxyapatite (CaHA) dermal filler has been increasingly used in facial aesthetic procedures.

OBJECTIVE
To investigate clinical and histological changes associated with calcium hydroxyapatite (CaHA) dermal filler in the orofacial region.

MATERIALS AND METHODS
Forty-eight female Wistar rats were divided into CaHA and control groups. The material was applied in the ventral tongue and the submandibular region; the animals were euthanized after 7, 30, and 90 days.

RESULTS
After 7 days, yellowish nodules with a firm consistency were observed on the tongue. In 2 animals, the material migrated to the base of the tongue. Histopathological examination revealed CaHA spheres surrounded by an infiltrate, predominantly composed of macrophages. In the CaHA group, the percentage of collagen in the tongue and dermis was higher compared with the control group (p < .05) at both 30 and 90 days. The thickness of the epidermis/dermis was also higher in the CaHA group (p < .05). In 5 submandibular glands containing material, areas of edema and hyperemia were observed, along with infiltrates of neutrophils, lymphocytes, and plasma cells. Changes in the morphology of ducts and acini in adjacent regions were evident.

CONCLUSION
CaHA exhibits satisfactory properties for filling and collagen biostimulation in the tested regions. Further studies are required to explore the potential for migration and the glandular alterations.
Inhibition of α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Receptors Ameliorates Atrial Inflammation and Vulnerability to Atrial Fibrillation in Rats with Anxiety Disorders
Authors: Zou Ying , Liu Xin , Hu Yiqian , Zhang Cui , Shen Bo , Yang Bo 
Published: June 2024

Abstract:
Previous studies have found that anxiety disorders may increase the incidence of atrial fibrillation (AF). More and more studies have shown that α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are involved in the occurrence and development of cardiovascular diseases. However, the role of AMPARs in AF associated with anxiety disorder remains unclear. The aim of this study was to investigate the effect of AMPARs on AF susceptibility in rats with anxiety disorder and its possible mechanism. The anxiety disorder rat model was established by unpredictable empty bottle stimulation and was treated with AMPARs agonist and antagonist. Our results showed that AMPARs antagonist treatment significantly reduced sympathetic activity, improved heart rate variability, shortened action potential duration, prolonged effective refractory period, reduced AF induction rate, and improved cardiac electrical remodeling and the expression of inflammatory factors. In addition, inhibition of AMPARs reduced the phosphorylation of IκBα and p65. Our experimental results suggest that inhibition of AMPARs can reduce autonomic remodeling, improve atrial electrical remodeling, and suppress myocardial inflammation, which provides a potential therapeutic strategy for the treatment of AF associated with anxiety disorder.