bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution of miRNA-Binding Sites and Regulatory Networks in Cichlids
Authors: Mehta Tarang K , Penso-Dolfin Luca , Nash Will , Roy Sushmita , Di-Palma Federica , Haerty Wilfried 
Published: June 2022

AbstractThe divergence of regulatory regions and gene regulatory network (GRN) rewiring is a key driver of cichlid phenotypic diversity. However, the contribution of miRNA-binding site turnover has yet to be linked to GRN evolution across cichlids. Here, we extend our previous studies by analyzing the selective constraints driving evolution of miRNA and transcription factor (TF)–binding sites of target genes, to infer instances of cichlid GRN rewiring associated with regulatory binding site turnover. Comparative analyses identified increased species-specific networks that are functionally associated to traits of cichlid phenotypic diversity. The evolutionary rewiring is associated with differential models of miRNA- and TF-binding site turnover, driven by a high proportion of fast-evolving polymorphic sites in adaptive trait genes compared with subsets of random genes. Positive selection acting upon discrete mutations in these regulatory regions is likely to be an important mechanism in rewiring GRNs in rapidly radiating cichlids. Regulatory variants of functionally associated miRNA- and TF-binding sites of visual opsin genes differentially segregate according to phylogeny and ecology of Lake Malawi species, identifying both rewired, for example, clade-specific and conserved network motifs of adaptive trait associated GRNs. Our approach revealed several novel candidate regulators, regulatory regions, and three-node motifs across cichlid genomes with previously reported associations to known adaptive evolutionary traits.
Comprehensive Genomic Profiling of 274 Thymic Epithelial Tumors Unveils Oncogenic Pathways and Predictive Biomarkers
Authors: Girard Nicolas , Basse Clémence , Schrock Alexa , Ramkissoon Shakti , Killian Keith , Ross Jeffrey S 
Published: June 2022

Abstract

Background
Thymic malignancies represent a heterogeneous group of rare thoracic cancers, which are classified according to the World Health Organization histopathologic classification, that distinguishes thymomas from thymic carcinomas. Data regarding the biology of those tumors are limited in the literature, and the vast majority have been obtained using surgical specimens from early-stage disease. Meanwhile, treatment of advanced, refractory thymic tumors currently relies on chemotherapy, with limited efficacy. Comprehensive genomic profiling (CGP) of advanced, refractory tumors would open some opportunities for innovative treatments.

Patients and Methods
A total of 90 and 174 consecutive patients with thymoma or thymic carcinoma, respectively, for whom formalin-fixed, paraffin-embedded specimens from recurrent, refractory tumor were sequenced, were included. Sequencing was performed using hybridization-captured, adaptor ligation-based libraries to a mean coverage depth of &gt;500× for up to 315 cancer-related genes plus 37 introns from 28 genes frequently rearranged in cancer.

Results
Thymomas featured a low frequency of genomic alterations (average of 1.8/tumor), and low levels of TMB. The genomic alterations identified in more than 10% of cases were in the CDKN2A/B and TP53 genes. Amplification in the NTRK1 gene was found in an unresectable, stage III, type B3 thymoma. Thymic carcinomas featured a significantly higher frequency of alterations at 4.0/tumor (P &lt; .0001). Clinically relevant genomic alterations were observed in the CDKN2A, KIT, and PTEN/PI3K/MTOR pathways. Elevated TMB in thymic carcinomas was uncommon with only 6% of cases featuring ≥10 mutations/Mb.

Conclusions
Our cohort is the largest available so far, reporting on CGP of thymic epithelial tumors in the setting of advanced disease. The identification of clinically relevant genomic alterations in the KIT, PI3K, CDKN2A/B, or NTRK genes provides a strong rationale for potential precision medicine approaches using targeted agents. A subset of thymic carcinomas show high tumor mutation burden, what may be a predictor of efficacy of immune checkpoint inhibitors.
Paws on the Street: Neighborhood-Level Concentration of Households with Dogs and Urban Crime
Authors: Pinchak Nicolo P , Browning Christopher R , Boettner Bethany , Calder Catherine A , Tarrence Jake 
Published: June 2022

AbstractThe formative work of Jane Jacobs underscores the combination of “eyes on the street” and trust between residents in deterring crime. Nevertheless, little research has assessed the effects of residential street monitoring on crime due partly to a lack of data measuring this process. We argue that neighborhood-level rates of households with dogs captures part of the residential street monitoring process core to Jacobs’ hypotheses and test whether this measure is inversely associated with property and violent crime rates. Data from a large-scale marketing survey of Columbus, OH, USA residents (2013; n = 43,078) are used to measure census block group-level (n = 595) rates of households with dogs. Data from the Adolescent Health and Development in Context study are used to measure neighborhood-level rates of trust. Consistent with Jacobs’ hypotheses, results indicate that neighborhood concentration of households with dogs is inversely associated with robbery, homicide, and, to a less consistent degree, aggravated assault rates within neighborhoods high in trust. In contrast, results for property crime suggest that the inverse association of dog concentration is independent of levels of neighborhood trust. These associations are observed net of controls for neighborhood sociodemographic characteristics, temporally lagged crime, and spatial lags of trust and dog concentration. This study offers suggestive evidence of crime deterrent benefits of local street monitoring and dog presence and calls attention to the contribution of pets to other facets of neighborhood social organization.
Gender Inequality in Lifetime Earnings
Authors: de Castro Galvao Juliana 
Published: June 2022

AbstractAlthough vast, most research on gender earnings gaps uses cross-sectional data for year-round full-time workers; therefore, little is known about the dynamics of gender inequality in lifetime earnings. To address this lacuna, this article analyzes data from the Panel Study of Income Dynamics from 1968 to 2017, to investigate the extent, trends and explanations of gender inequality in lifetime earnings both within and across five birth cohorts born between 1930 and 1979. I find that the lifetime gap sharply declined until the 1960s birth cohort, with little change thereafter. Unpacking trends throughout the lifecycle shows that this stalled gender convergence is driven by increasing gender earnings inequality throughout the prime working years of those born in the 1960s and 1970s. Decomposition of the lifetime earnings gap further reveals that gender differences in the number of hours worked throughout one’s working life is a more important factor for younger rather than older generations—despite gender convergence in lifetime labor force attachment across cohorts. On the other hand, gender inequality in stop-outs during early career has become a less relevant factor in explaining earnings differences for younger generations. These findings draw attention to the value of examining gender inequality as a cumulative long-term process.
Sarcopenia, body composition and factors associated with variceal gastrointestinal bleeding and splenectomy in hepatosplenic schistosomiasis mansoni
Authors: Barbosa Fernanda A , Nardelli Mateus J , Cançado Guilherme G L , Silva Catherine F , Osório Fernanda M F , Melo Rodolfo F Q , Taranto Daniela O L , Ferrari Teresa C A , Couto Claudia A , Faria Luciana C 
Published: June 2022

Abstract

Background
Sarcopenia is a common complication of cirrhosis and an important predictor of morbimortality. We aimed to determine the prevalence of sarcopenia and its associated factors in hepatosplenic schistosomiasis (HSS) as well as to evaluate whether muscle mass and function are associated with variceal upper gastrointestinal bleeding (VUGIB) and previous splenectomy in subjects without other liver diseases.

Methods
We conducted a cross-sectional study including adults with HSS who underwent clinical, biochemical, anthropometric, muscle strength and physical performance evaluations and were submitted to bioelectrical impedance analysis and abdominal ultrasound. Sarcopenia was diagnosed according to the 2019 European consensus criteria.

Results
A total of 66 patients with HSS (62.1% male; mean age 48.8±8.6 y) were included. Overall, six subjects (9.1%) were diagnosed with probable sarcopenia and none had confirmed sarcopenia. Fat-free body mass index (BMI) was independently associated with VUGIB (odds ratio 0.701 [95% confidence interval 0.51 to 0.96]; p=0.025). Compared with patients who did not undergo surgery, individuals who underwent esophagogastric devascularization combined with splenectomy (EGDS) had higher serum lipid levels, fat percentage and frequency of metabolic syndrome, with lower skeletal muscle mass index and hand grip strength.

Conclusions
HSS mansoni seems not to cause sarcopenia. However, a lower fat-free BMI was associated with previous VUGIB and the subgroup of patients who underwent EGDS presented higher lipid levels, fat percentage and frequency of metabolic syndrome and lower muscle mass and function.
Nephrin expression in human epidermal keratinocytes and its implication in poor wound closure
Authors: Kim Ji Young , Lee Eun Jung , Seo Jimyung , Lee Yangsin , Ahn Yuri , Park Sujin , Bae Yu Jeong , Lee Jinu , Lim Beom Jin , Kim Doyoung , Cho Jin Won , Oh Sang Ho 
Published: June 2022

AbstractNephrin is a type‐1 transmembrane protein and a component of the slit diaphragm renal‐filtration barrier. It has several functions in actin remodeling and cell–cell adhesion. Nephrin is principally located in the kidney glomerulus, but several studies have reported that nephrin is found in the pancreas, brain, and placenta. However, nephrin expression and its role in human skin have not yet been reported. First, using single‐cell RNA sequencing, immunohistochemistry, and immuno‐electron microscopy, nephrin expression was confirmed in human‐skin epidermal keratinocytes. Nephrin expression colocalized with the expression of zonula occludens‐1 in keratinocytes and was closely related to keratinocyte cell density, proliferation, and migration. High glucose treatment decreased nephrin expression and compromised keratinocyte cell migration without yes‐associated protein nuclear entry. This reduced cell migration under high glucose conditions was improved in nephrin‐overexpressing keratinocytes. Nephrin was highly expressed on the margins of re‐epithelized epidermis based on in vivo mice and ex vivo human skin wound models. The results demonstrate that nephrin is expressed in human‐skin keratinocytes and functions in cell adhesion, proliferation, and migration. In conclusion, this study suggests that nephrin may have a variety of physiological roles in human skin.
Global analyses of mRNA expression in human sensory neurons reveal eIF5A as a conserved target for inflammatory pain
Authors: Chase Rebecca , de la Peña June Bryan , Smith Patrick R. , Lawson Jennifer , Lou Tzu‐Fang , Stanowick Alexander D. , Black Bryan J. , Campbell Zachary T. 
Published: June 2022

AbstractNociceptors are a type of sensory neuron that are integral to most forms of pain. Targeted disruption of nociceptor sensitization affords unique opportunities to prevent pain. An emerging model for nociceptors are sensory neurons derived from human stem cells. Here, we subjected five groups to high‐throughput sequencing: human induced pluripotent stem cells (hiPSCs) prior to differentiation, mature hiPSC‐derived sensory neurons, mature co‐cultures containing hiPSC‐derived astrocytes and sensory neurons, mouse dorsal root ganglion (DRG) tissues, and mouse DRG cultures. Co‐culture of nociceptors and astrocytes promotes expression of transcripts enriched in DRG tissues. Comparisons of the hiPSC models to tissue samples reveal that many key transcripts linked to pain are present. Markers indicative of a range of neuronal subtypes present in the DRG were detected in mature hiPSCs. Intriguingly, translation factors were maintained at consistently high expression levels across species and culture systems. As a proof of concept for the utility of this resource, we validated expression of eukaryotic initiation factor 5A (eIF5A) in DRG tissues and hiPSC samples. eIF5A is subject to a unique posttranslational hypusine modification required for its activity. Inhibition of hypusine biosynthesis prevented hyperalgesic priming by inflammatory mediators in vivo and diminished hiPSC activity in vitro. Collectively, our results illuminate the transcriptomes of hiPSC sensory neuron models. We provide a demonstration for this resource through our investigation of eIF5A. Our findings reveal hypusine as a potential target for inflammation associated pain in males.
The Impact of Isolated Versus Multiple Osteochondromas: Analysis of the CoULD Registry
Authors: Wessel Lauren E. , Goldfarb Charles A. , Vuillermin Carley , Hutchinson Douglas T. , Bohn Deborah , Steinman Suzanne , Wall Lindley B. ,   CoULD Study Group
Published: June 2022

Purpose:The burden of upper extremity (UE) osteochondromas on function and self-perception among pediatric patients is unclear. The purpose of our study was to study the impact of osteochondromas in comparison to population norms and to evaluate solitary versus multiple osteochondromas on subjective UE function as measured by patient rated outcomes.Methods:We utilized the CoULD (Congenital Upper Limb Differences) Registry to review all pediatric patients presenting with osteochondromas between January 2014 and February 2021. Demographic information was collected and patients were classified as having either single or multiple osteochondromas. Patient-Reported Outcome Measurement Information System (PROMIS) and Pediatric Outcomes Data Collection Instrument (PODCI) tools were utilized for assessment. Scores for PODCI subscales of UE function, Pain/comfort, and Happiness and PROMIS domains of UE Function, Pain, Depression, Anxiety, and Peer Relations were reviewed. Differences between groups were analyzed using the Studentttest.Results:Ninety-nine patients met inclusion criteria for the study with an average age of presentation of 9.3 years and 61 patients (62%) were male. Overall, patients demonstrated worse UE Function as well as greater Anxiety and Depression in comparison to the population normals on PROMIS assessment. Patients also demonstrated worse patient and parent reported PODCI UE, Sports and Physical Functioning, Pain/Comfort and Global Functioning scores compared with population norms but demonstrated better than average happiness scores. Patients with multiple osteochondromas demonstrated greater PROMIS pain interference and more disability in PODCI Sports and Physical Functioning, Pain/Comfort and Global Functioning compared with those with solitary osteochondromas.Conclusion:Patients with UE osteochondromas have worse overall function in comparison to population norms, exceeding established minimally clinically important difference values. In addition, patients with multiple osteochondromas reported more pain and poorer physical function than those with solitary osteochondromas. Physicians should be alert to the physical and psychosocial burden of this disease.Level of Evidence:Level II—prognostic.
Abuse Potential of Lemborexant, a Dual Orexin Receptor Antagonist, Compared With Zolpidem and Suvorexant in Recreational Sedative Users
Authors: Landry Ishani , Hall Nancy , Aluri Jagadeesh , Filippov Gleb , Reyderman Larisa , Setnik Beatrice , Henningfield Jack , Moline Margaret 
Published: June 2022

Abstract

Background
Lemborexant (LEM) is a dual orexin receptor antagonist approved for the treatment of insomnia in adults in multiple countries including the the United States, Japan, Canada, Australia and several Asian countries.

Procedures
This was a randomized, single-dose, single-center, double-blind, active-control, 6-way crossover study to evaluate LEM abuse potential. The study assessed oral doses of LEM 10 mg (LEM10), 20 mg (LEM20), and 30 mg (LEM30) compared with placebo (PBO), zolpidem (ZOL) immediate release 30 mg, and suvorexant (SUV) 40 mg. Subjects were healthy, nondependent, recreational sedative users able to discriminate/like the effects of both SUV and ZOL from PBO during a qualification phase.

Results
Abuse potential endpoints were analyzed in qualified subjects who received and completed all treatments (n = 32). On the “at this moment” drug-liking visual analog scale (VAS), mean maximum (peak) effect (primary endpoint) values were 78.4, 80.5, and 83.6 for LEM10, LEM20, and LEM30, respectively, which were all significantly greater than PBO (57.8; all P > 0.05) but not different from SUV (76.1) or ZOL (78.3). Similarly, for secondary endpoints overall drug-liking VAS and take-drug-again VAS, mean maximum (peak) effect values for all LEM doses were significantly greater than PBO (P > 0.05) but not different compared with ZOL or SUV.

Conclusions
For all doses, LEM demonstrated abuse potential versus PBO and appeared to have a similar abuse potential profile to ZOL and SUV in this study population. Lemborexant was well tolerated. Lemborexant has been placed in Schedule IV, the same drug schedule as ZOL and SUV.
Pandemic response: The identification of alternative clinical hours to ensure advanced practice nursing students meet program requirements
Authors: Bricker Christina , Canale Michelle , Hay Brittany , Taylor Tracey , Maguire Denise , Remo Elizabeth , Smith Sharlene , Johansson Marcia , Morgan Hailey 
Published: June 2022

ABSTRACT
The coronavirus (COVID-19) pandemic resulted in the abrupt withdrawal of clinical sites for advanced practice nursing students which worsened an already challenging placement process. Few studies to date have analyzed the use of alternative clinical practice experiences used to facilitate the completion of program requirements by advanced practice nursing students beyond direct hour requirements. The faculty team from one university decided to track and analyze their use of alternative clinical practice experiences for advanced practice nursing students actively enrolled during the first semester of the pandemic. The team collated student alternative hour entries within the clinical courses for review and statistical analysis. Data included input from advanced practice nursing students in family, pediatric primary care, adult gerontology primary care, adult gerontology acute care nurse practitioner concentrations, and nursing education, doctor of nursing practice, and nurse anesthesia programs. A total of 569 advanced practice nursing students participated in 15 distinct alternative clinical activities. There was a significant effect of students' program concentration on total number of virtual case study hours logged, F(6, 562) = 9.45, p < .0001, and a significant effect of students' program concentration on total number of continuing education hours logged, F(6, 562) = 7.79, p < .0001. Results can inform the use of concentration-specific alternative activities for advanced practice nursing students to address gaps in clinical experiences.
Accuracy and Interrater Reliability of Point-of-Care Ultrasonography Image Interpretation for Intussusception
Authors: Bergmann Kelly R. , Khant Marshal , Lammers Shea , Arroyo Alexander C. , Avendano Pablo , Chaudoin Lindsey , Cohen Stephanie G. , Deanehan J. Kate , Kornblith Aaron E. , Lam Samuel H. F. , Lin-Martore Margaret , Malia Laurie , Pade Kathryn H. , Park Daniel B. , Sivitz Adam , Shahar-Nissan Keren , Snelling Peter J. , Tessaro Mark O. , Thomas-Mohtat Rosemary , Whitcomb Valerie , Yock-Corrales Adriana , Walsh Paige , Watson Dave , Madhok Manu ,   In Collaboration with the P2Network Intussusception Study Group
Published: June 2022

ObjectivesThe aim of this study was to determine the accuracy and interrater reliability of (1) point-of-care ultrasound (POCUS) image interpretation for identification of intussusception and (2) reliability of secondary signs associated with intussusception among experts compared with novice POCUS reviewers.MethodsWe conducted a planned secondary analysis of a prospective, convenience sample of children aged 3 months to 6 years who were evaluated with POCUS for intussusception across 17 international pediatric emergency departments between October 2018 and December 2020. A random sample of 100 POCUS examinations was reviewed by novice and expert POCUS reviewers. The primary outcome was identification of the presence or absence of intussusception. Secondary outcomes included intussusception size and the presence of trapped free fluid or echogenic foci. Accuracy was summarized using sensitivity and specificity, which were estimated via generalized mixed effects logistic regression. Interrater reliability was summarized via Light's κ statistics with bootstrapped standard errors (SEs). Accuracy and reliability of expert and novice POCUS reviewers were compared.ResultsEighteen expert and 16 novice POCUS reviewers completed the reviews. The average expert sensitivity was 94.5% (95% confidence interval [CI], 88.6–97.5), and the specificity was 94.3% (95% CI, 90.3–96.7), significantly higher than the average novice sensitivity of 84.7% (95% CI, 74.3–91.4) and specificity of 80.4% (95% CI, 72.4, 86.7). κ was significantly greater for expert (0.679, SE 0.039) compared with novice POCUS reviewers (0.424, SE 0.044; difference 0.256, SE 0.033). For our secondary outcome measure of intussusception size, κ was significantly greater for experts (0.661, SE 0.038) compared with novices (0.397, SE 0.041; difference 0.264, SE 0.029). Interrater reliability was weak for expert and minimal for novice reviewers regarding the detection of trapped free fluid and echogenic foci.ConclusionsExpert POCUS reviewers demonstrate high accuracy and moderate interrater reliability when identifying intussusception via image interpretation and perform better than novice reviewers.
Recipient Selection Criteria for Facial Transplantation
Authors: Parker Augustus , Chaya Bachar F. , Rodriguez-Colon Ricardo , Hao Yvonne , Kurian Keerthi , Trilles Jorge , Boczar Daniel , Brydges Hilliard , Rodriguez Eduardo D. 
Published: June 2022

BackgroundRecipient selection is an important determinant of surgical outcomes in facial transplantation (FT). Appropriately, each FT program develops their own guidelines for recipient selection criteria. Currently, there is no resource to simultaneously assess and identify similarities and differences between these guidelines. Such information could be useful in distinguishing areas of FT that are well understood from those that could benefit from further exploration.MethodsWe performed a systematic review of the scientific literature from inception to June 18, 2021, using Pubmed, Embase, Cochrane Library, and Scopus to identify articles pertaining to recipient selection criteria. Clinical trials were identified through the Clinicaltrials.gov registry. United States and international program websites were reviewed for patient-facing information.ResultsOur systematic review yielded 90 suitable articles, 8 clinical trials, and 7 program websites containing the recipient selection criteria of 24 different FT programs. The most reported on recipient criteria were age, positive human immunodeficiency viral status (HIV+), positive hepatitis C viral status, psychosocial stability, and medical compliance. Other criteria were rarely addressed, such as blindness and recipient immune status.ConclusionsGuidelines among different face transplant programs are changing over time. We found consensus on certain recipient selection criteria, but the majority remain program or surgeon dependent, emphasizing that FT is still an evolving procedure. Although most programs reported on their recipient selection criteria, the rationale was often missing. Further discussion about recipient selection criteria and the reasoning behind employing or changing them will help advance the field.