bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomechanical properties of the lips in a pre-orthodontic sample of adolescents and young adults
Authors: Hodgkinson Danielle , Prasad Sabarinath , Antoun Joseph S , Mei Li , Farella Mauro 
Published: July 2021

SummaryObjectivesTo assess biomechanical properties of the lip muscles and to investigate their relationship with sex, age, body mass index (BMI), and cephalometric variables.Materials and methodsDemographic information and BMI were collected from 83 study participants seeking orthodontic treatment at the University of Otago. Tone, stiffness, and elasticity of the lip muscles were measured thrice at four different anatomical sites using a digital palpation device. To estimate method error, a duplicate set of measurements in a subsample of 20 participants was taken a week later. Sagittal and vertical cephalometric classifications were based on ANB and FMPA angles, respectively. Data were analysed using mixed models.ResultsBiomechanical properties of lip muscles were remarkably consistent both within and between different recording sessions. The lower lip had higher tone and stiffness than the upper lip. Both the upper and lower lip stiffness and tone were higher in females than in males, whereas upper lip elasticity was higher in males. Thinner upper lips had higher tone and were stiffer than thicker upper lips, whereas thinner lower lips were less elastic than thicker lower lips. Muscle tone and stiffness of both the upper and lower lips were lower in Class III than in Class I and Class II individuals. The upper lip of hyperdivergent individuals was less elastic than that of normodivergent and hypodivergent individuals, and stiffer than that of hypodivergent individuals.ConclusionsThe biomechanical properties of perioral soft tissues can be reliably measured and vary with anatomical site, sex, and cephalometric measurements.
Experimental mindset for environmental challenges: the puzzling case of public good contributions
Authors: Shogren Jason F , Hochard Jacob , Lee Katherine D , Varelas Henderson Leticia 
Published: July 2021

Abstract
The experimental mindset strips down and mimics social constructs in a setting we can use to understand how institutions create or destroy economic value. We explore how to use the mindset to consider climate change mitigation, in which more investment in climate mitigation by the collective, the less costly for each party. Using the lab to capture Conference of the Parties declining-cost environment with a jigsaw puzzle to mimic real-time costs, we find decreasing ‘cost’ of commitment increases contribution but not reaching the public good threshold. Highlighting the economies of scale might be an effective way to elicit greater commitment.
Interpretable artificial neural networks incorporating Bayesian alphabet models for genome-wide prediction and association studies
Authors: Zhao Tianjing , Fernando Rohan , Cheng Hao 
Published: July 2021

Abstract
In conventional linear models for whole-genome prediction and genome-wide association studies (GWAS), it is usually assumed that the relationship between genotypes and phenotypes is linear. Bayesian neural networks have been used to account for non-linearity such as complex genetic architectures. Here, we introduce a method named NN-Bayes, where “NN” stands for neural networks, and “Bayes” stands for Bayesian Alphabet models, including a collection of Bayesian regression models such as BayesA, BayesB, BayesC, and Bayesian LASSO. NN-Bayes incorporates Bayesian Alphabet models into non-linear neural networks via hidden layers between single-nucleotide polymorphisms (SNPs) and observed traits. Thus, NN-Bayes attempts to improve the performance of genome-wide prediction and GWAS by accommodating non-linear relationships between the hidden nodes and the observed trait, while maintaining genomic interpretability through the Bayesian regression models that connect the SNPs to the hidden nodes. For genomic interpretability, the posterior distribution of marker effects in NN-Bayes is inferred by Markov chain Monte Carlo approaches and used for inference of association through posterior inclusion probabilities and window posterior probability of association. In simulation studies with dominance and epistatic effects, performance of NN-Bayes was significantly better than conventional linear models for both GWAS and whole-genome prediction, and the differences on prediction accuracy were substantial in magnitude. In real-data analyses, for the soy dataset, NN-Bayes achieved significantly higher prediction accuracies than conventional linear models, and results from other four different species showed that NN-Bayes had similar prediction performance to linear models, which is potentially due to the small sample size. Our NN-Bayes is optimized for high-dimensional genomic data and implemented in an open-source package called “JWAS.” NN-Bayes can lead to greater use of Bayesian neural networks to account for non-linear relationships due to its interpretability and computational performance.
Selective functional inhibition of a tumor-derived p53 mutant by cytosolic chaperones identified using split-YFP in budding yeast
Authors: Denney Ashley S , Weems Andrew D , McMurray Michael A 
Published: July 2021

Abstract
Life requires the oligomerization of individual proteins into higher-order assemblies. In order to form functional oligomers, monomers must adopt appropriate 3D structures. Molecular chaperones transiently bind nascent or misfolded proteins to promote proper folding. Single missense mutations frequently cause disease by perturbing folding despite chaperone engagement. A misfolded mutant capable of oligomerizing with wild-type proteins can dominantly poison oligomer function. We previously found evidence that human-disease-linked mutations in Saccharomyces cerevisiae septin proteins slow folding and attract chaperones, resulting in a kinetic delay in oligomerization that prevents the mutant from interfering with wild-type function. Here, we build upon our septin studies to develop a new approach for identifying chaperone interactions in living cells, and use it to expand our understanding of chaperone involvement, kinetic folding delays, and oligomerization in the recessive behavior of tumor-derived mutants of the tumor suppressor p53. We find evidence of increased binding of several cytosolic chaperones to a recessive, misfolding-prone mutant, p53(V272M). Similar to our septin results, chaperone overexpression inhibits the function of p53(V272M) with minimal effect on the wild type. Unlike mutant septins, p53(V272M) is not kinetically delayed under conditions in which it is functional. Instead, it interacts with wild-type p53 but this interaction is temperature sensitive. At high temperatures or upon chaperone overexpression, p53(V272M) is excluded from the nucleus and cannot function or perturb wild-type function. Hsp90 inhibition liberates mutant p53 to enter the nucleus. These findings provide new insights into the effects of missense mutations.
Trajectories of Frailty in the 5 Years Prior to Death Among U.S. Veterans Born 1927–1934
Authors: Ward Rachel E , Orkaby Ariela R , Dumontier Clark , Charest Brian , Hawley Chelsea E , Yaksic Enzo , Quach Lien , Kim Dae H , Gagnon David R , Gaziano J Michael , Cho Kelly , Djousse Luc , Driver Jane A 
Published: July 2021

Abstract

Background
Electronic frailty indices (eFIs) are increasingly used to identify patients at risk for morbidity and mortality. Whether eFIs capture the spectrum of frailty change, including decline, stability, and improvement, is unknown.

Methods
In a nationwide retrospective birth cohort of U.S. Veterans, a validated eFI, including 31 health deficits, was calculated annually using medical record and insurance claims data (2002–2012). K-means clustering was used to assign patients into frailty trajectories measured 5 years prior to death.

Results
There were 214 250 veterans born between 1927 and 1934 (mean [SD] age at death = 79.4 [2.8] years, 99.2% male, 90.3% White) with an annual eFI in the 5 years before death. Nine frailty trajectories were identified. Those starting at nonfrail or prefrail had 2 stable trajectories (nonfrail to prefrail, n = 29 786 and stable prefrail, n = 28 499) and 2 rapidly increasing trajectories (prefrail to moderately frail, n = 28 244 and prefrail to severely frail, n = 22 596). Those who were mildly frail at baseline included 1 gradually increasing trajectory (mildly to moderately frail, n = 33 806) and 1 rapidly increasing trajectory (mildly to severely frail, n = 15 253). Trajectories that started at moderately or severely frail included 2 gradually increasing trajectories (moderately to severely frail, n = 27 662 and progressing severely frail, n = 14 478) and 1 recovering trajectory (moderately frail to mildly frail, n = 13 926).

Conclusions
Nine frailty trajectories, including 1 recovering trajectory, were identified in this cohort of older U.S. Veterans. Future work is needed to understand whether prevention and treatment strategies can improve frailty trajectories and contribute to compression of morbidity toward the end of life.
Functional assessment of two variants of unknown significance in TEK by endothelium-specific expression in zebrafish embryos
Authors: Bell Lorenz M , Holm Annegret , Matysiak Uta , Driever Wolfgang , Rößler Jochen , Schanze Denny , Wieland Ilse , Niemeyer Charlotte M , Zenker Martin , Kapp Friedrich G 
Published: July 2021

Abstract
Vascular malformations are most often caused by somatic mutations of the PI3K/mTOR and the RAS signaling pathways, which can be identified in the affected tissue. Venous malformations (VMs) commonly harbor PIK3CA and TEK mutations, whereas arteriovenous malformations (AVMs) are usually caused by BRAF, RAS or MAP2K1 mutations. Correct identification of the underlying mutation is of increasing importance, since targeted treatments are becoming more and more relevant, especially in patients with extensive vascular malformations. However, variants of unknown significance (VUSs) are often identified and their pathogenicity and response to targeted therapy cannot be precisely predicted. Here, we show that zebrafish embryos can be used to rapidly assess the pathogenicity of novel VUSs in TEK, encoding for the receptor TIE2, present on endothelial cells of VMs. Endothelium-specific overexpression of TEK mutations leads to robust induction of VMs, whereas MAP2K1 mutations cause AVMs in our zebrafish model. TEK mutations are often found as double mutations in cis; using our model, we show that double mutations have an additive effect in inducing VMs compared with the respective single variants. The clinically established mTOR-inhibitor sirolimus (rapamycin) efficiently abrogates the development of VMs in this zebrafish model. In summary, endothelium-specific overexpression of patient-derived TEK variants in the zebrafish model allows assessment of their pathogenic significance as well as testing of candidate drugs in a personalized and mutation-specific approach.
A Framework for Clinical Trials of Neurobiological Interventions That Target the Gut-Brain Axis in Inflammatory Bowel Disease
Authors: Tse Chung Sang , Singh Siddharth , Sandborn William J 
Published: July 2021

Abstract
A growing body of evidence from preclinical, translational, and clinical studies supports a bidirectional relationship within the gut-brain axis that contributes to neurobiological symptoms including anxiety, depression, fatigue, stress, and sleep disturbance. These symptoms have a significant impact on health-related quality of life and functional ability in individuals with inflammatory bowel disease. Clinical studies that generate high-quality evidence on pharmacological and nonpharmacological (eg, psychosocial, behavioral) interventions are needed to ultimately improve access to safe and effective therapies that have a meaningful impact on patients and to guide medical and regulatory decisions. This review outlines a framework for designing and conducting randomized controlled trials for interventions that target neurobiological symptoms in patients with inflammatory bowel disease based on the most recent guidance published within the past 5 years from policy makers, clinicians specialized in inflammatory bowel disease, patient-reported outcomes methodologists, health economists, patient advocates, industry representatives, ethicists, and clinical trial experts.
Efficacy of Vedolizumab in a Nationwide Cohort of Elderly Inflammatory Bowel Disease Patients
Authors: Khan Nabeel , Pernes Tyler , Weiss Alexandra , Trivedi Chinmay , Patel Manthankumar , Medvedeva Elina , Xie Dawei , Yang Yu-Xiao 
Published: July 2021

Abstract

Background
The elderly inflammatory bowel disease (IBD) population has historically been under-represented in clinical trials, and data on the efficacy of biologic medications in elderly IBD patients are generally lacking. Our study aims to evaluate the efficacy of vedolizumab (VDZ) among elderly IBD patients and compare it with younger IBD patients in a nationwide population-based cohort of IBD patients.

Methods
We conducted a retrospective cohort study of patients within the US national Veterans Affairs Healthcare System (VAHS). Patients were stratified into 2 groups based on age at the time of starting VDZ (60 years of age and older or younger than 60 years of age) with outcomes compared between the 2 groups. The primary outcome was steroid-free remission during the 6- to 12-month period after starting VDZ therapy among those patients who were on steroids when VDZ was started.

Results
There were 568 patients treated with VDZ, of whom 56.7% had Crohn’s disease and 43.3% had ulcerative colitis. Among them, 316 patients were on steroids when VDZ was started. The percentage of patients who were on VDZ and off steroids during the 6- to 12-month period after VDZ initiation was 46.8% and 40.1% for the younger and elderly groups, respectively (P = 0.2374). Rates of hospitalization for an IBD-related reason within 1 year of VDZ start among the whole cohort were nearly identical in the younger and elderly groups (11.2% vs 11.3%, P = 0.9737). Rates of surgery for an IBD-related reason within 1 year of VDZ start were also similar between the young and elderly (3.9% vs 3.9%, P = 0.9851).

Conclusions
In a nationwide real-world retrospective cohort study of elderly IBD patients, we found that the efficacy of VDZ was similar among younger and older IBD patients and comparable with the published data in clinical trials.
From Flatland to Jupiter: Searching for Rules of Interaction Across Biological Scales
Authors: Grillo Claudia A , Holford Mandë , Walter Nils G 
Published: July 2021

Synopsis
In this future-spanning perspective, we examine how an agent-based model could be used to define general rules for interactions across biological systems and evolutionary time. To date, there have been a number of attempts to simulate the emergence of ecological communities using agent-based models of individuals that have evolving traits. Here we speculate whether it is possible to use this computational modeling to simulate self-organizing systems and, importantly, to decipher universal principles that govern biological interactions. This perspective is a thought exercise, meant to extrapolate from current knowledge to how we may make Jupiter-shot leaps to further advance the biosciences in the 21st century.
Reduced Infestation by Xylosandrus germanus (Coleoptera: Curculionidae: Scolytinae) in Apple Trees Treated with Host Plant Defense Compounds
Authors: Agnello Arthur M , Combs David B , Filgueiras Camila C , Willett Denis S , Mafra-Neto Agenor 
Published: July 2021

Abstract
The ambrosia beetle Xylosandrus germanus (Blandford) is an invasive pest that has caused tree decline and death in numerous NY dwarf apple orchards during the past ten years, despite efforts to control them using trunk sprays of chlorpyrifos or pyrethroids, either alone or combined with the repellent verbenone. From 2017 to 2019, we tested trunk applications of different repellents and plant defense compounds for protection against X. germanus in potted apple trees adjacent to infested orchards. Treatments included topical formulations of verbenone and methyl salicylate (MeSa), alone and in combination, at different rates and timings. Additional treatments evaluated included the systemic acquired resistance activators acibenzolar-S-methyl, Reynoutria sachalinensis extract, and salicylic acid. The combination verbenone+MeSa treatments had the lowest incidences of attack sites and galleries containing adults or brood, although results varied among years. In a separate trial, we found no significant difference in numbers of adults caught in ethanol-baited traps placed 5–20 m from an apple bolt treated with the verbenone+MeSa repellent, suggesting that the repellent’s effect did not extend to those distances from the treated target. Cross-sectional discs of trunk tissue sampled in August were analyzed for levels of phytohormones. Quantities of ergosterol, abscissic acid, salicylic acid, jasmonic acid, methyl salicylate, methyl jasmonate, trans-cinnamic acid, and indole-3-cinnamic acid did not significantly vary across treatments; however, trees with greater beetle damage contained higher levels of jasmonic and salicylic acid, which are key molecules in plant defense pathways.
Implementation of Direct Access Physical Therapy Within the Military Medical System
Authors: Szymanek Eliza , Jones Megan , Shutt-Hoblet Casey , Halle Robert 
Published: July 2021

ABSTRACT

Introduction
Readiness is the Army’s number one priority. Physical therapists (PTs) are musculoskeletal (MSK) experts and have been serving as physician extenders in a direct access role in the military since Vietnam. Utilizing a PT in the direct access role has demonstrated a reduction in imaging, medication prescribed, number of physical therapy visits, and overall reduction in healthcare utilization.

Materials and Methods
The Joint Base Lewis-McChord physical therapy service line initiated a readiness-focused direct access initiative in May 2018. A simple algorithm was developed to help screen and identify appropriate service members for direct access physical therapy sick call. Physical therapy sick call hours were established at seven Joint Base Lewis-McChord Physical Therapy clinics.

Results
During the initial 18 months of this direct access PT initiative, a total of 3,653 initial physical therapy evaluations were completed. Injury location included 26% (953) knee, 26% (945) ankle, 16% (585) low back, 15% (551) shoulder, 9% (316) hip, and 8% (303) leg.

Conclusion
In the military, where readiness is the number one priority, it is essential that we optimize the medical resources available to our service members in order to minimize lost duty days and overall long-term disability. This project demonstrates a way to optimize the military healthcare system in order to reduce cost and healthcare utilization and minimize duty days lost to MSK injuries. Utilizing a conservative estimate, $3.6 million was potentially saved in military healthcare utilization costs. The subanalysis performed at one clinic comparing referral-based care with the direct access model demonstrated a reduction in imaging, days on profile, cost savings, reduction in referral to specialty care, and decreased long-term disability. In the military healthcare system, where our primary care team resources are limited, it is important to consider the PT as part of the acute MSK injury management team.
Increased Scholarly Activity: A Benefit of 4-Year Family Medicine Residencies
Authors: Sullivan John F , Keck James W , Stephens Mark B , O’Connell Tara A , Smith Dustin K , Sanchack Kristian E , Lennon Robert P 
Published: July 2021

ABSTRACTIntroductionThe optimal length of Family Medicine Residency is unknown. As part of the American Board of Family Medicine 4-year Length of Training (LoT) pilot project, Naval Hospital Jacksonville (NHJ) maintained a dual-track 3- and 4-year Family Medicine Residency, graduating seven 4-year residents over consecutive 4 years of the LoT program. One measure of success regarding the impact of 4-year residents on program outcomes is scholarly output during residency.Materials and MethodsCumulative scholarly activity points are tracked for all NHJ residents. Cumulative scholarly activity points, points per year per, and raw percentile USMLE/COMLEX scores from academic years 2016–17 to 2019–20 were compared between PGY3 and PGY4 graduates using one-way ANOVA to 95% confidence with post hoc Tukey honestly significant difference pairwise comparison to evaluate pairwise significance between groups where multi-group differences were found.ResultsDuring the 2016–17 through 2019–20 academic years, NHJ had 28 residents complete 3 years of training without interruption (3 Years), 11 residents complete 3 years of training interrupted by general medical officer tours (Resiterns), and 7 residents complete 4 years of training without interruption (4 Years). There were no significant differences in average raw USMLE and COMLEX scores between 3 Year (71%), Resitern (68%), and 4 Year (76%) residents (P = .335). 4-Year residents had significantly more cumulative scholarly points (103) than 3-Year residents (32.6, P &lt; .001) and Resiterns (18.7, P &lt; .001) and also had more cumulative scholarly points per year of residency (27.8) than 3-Year residents (9.8, P &lt; .001) and Resiterns (7.0, P &lt; .001).ConclusionsAn observed benefit of a 4-year Family Medicine Residency was a marked increase in scholarly output at this program.
Origin of metals in old Milky Way halo stars based on GALAH and Gaia
Authors: Ishigaki Miho N , Hartwig Tilman , Tarumi Yuta , Leung Shing-Chi , Tominaga Nozomu , Kobayashi Chiaki , Magg Mattis , Simionescu Aurora , Nomoto Ken’ichi 
Published: July 2021

ABSTRACT
Stellar and supernova nucleosynthesis in the first few billion years of the cosmic history have set the scene for early structure formation in the Universe, while little is known about their nature. Making use of stellar physical parameters measured by GALAH Data Release 3 with accurate astrometry from the Gaia EDR3, we have selected ∼100 old main-sequence turn-off stars (ages ≳12 Gyr) with kinematics compatible with the Milky Way stellar halo population in the Solar neighbourhood. Detailed homogeneous elemental abundance estimates by GALAH DR3 are compared with supernova yield models of Pop III (zero-metal) core-collapse supernovae (CCSNe), normal (non-zero-metal) CCSNe, and Type Ia supernovae (SN Ia) to examine which of the individual yields or their combinations best reproduce the observed elemental abundance patterns for each of the old halo stars (‘OHS’). We find that the observed abundances in the OHS with [Fe/H] &gt; −1.5 are best explained by contributions from both CCSNe and SN Ia, where the fraction of SN Ia among all the metal-enriching SNe is up to 10–20 per cent for stars with high [Mg/Fe] ratios and up to 20–27 per cent for stars with low [Mg/Fe] ratios, depending on the assumption about the relative fraction of near-Chandrasekhar-mass SNe Ia progenitors. The results suggest that, in the progenitor systems of the OHS with [Fe/H] &gt; −1.5, ∼ 50–60 per cent of Fe mass originated from normal CCSNe at the earliest phases of the Milky Way formation. These results provide an insight into the birth environments of the oldest stars in the Galactic halo.