bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Patient Sex and Graft Type on Postoperative Functional Outcomes After Primary ACL Reconstruction
Authors: Lesevic Milos , Kew Michelle E. , Bodkin Stephan G. , Diduch David R. , Brockmeier Stephen F. , Miller Mark D. , Gwathmey F. Winston , Werner Brian C. , Hart Joseph M. 
Published: June 2020

Background: Graft choice in anterior cruciate ligament reconstruction (ACLR) and postoperative rehabilitation may affect strength recovery differently in men than women and therefore affect a timely and successful return to sport. Purpose: To compare knee extensor and flexor strength between men and women who underwent isolated ACLR with either patellar tendon or hamstring tendon (HST) autografts. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 166 patients (87 women, 79 men) with primary unilateral and uncomplicated ACLRs were recruited for participation. A total of 100 patients had bone–patellar tendon–bone (BPTB) autografts and 66 had HST autografts. At 6 months postoperatively, all patients completed the Tegner activity scale and International Knee Documentation Committee Subjective Knee Evaluation as well as underwent bilateral isokinetic (90 deg/s) tests of the knee extensor and flexor groups. Outcomes were recorded in a single session as part of a return-to-sport test battery. Surgical notes were obtained to determine the type of autograft and nerve block used at the time of ACLR. Results: There was a significant sex × graft type interaction for mass-normalized knee flexor torque ( P = .017). Female patients with an HST graft had a significantly lower knee flexor torque compared with female patients with a BPTB graft (0.592 ± 0.49 N·m/kg vs 0.910 ± 0.24 N·m/kg; Cohen d [95% CI] = 0.91 [0.45, 1.36]). They also had a significantly lower knee flexor torque when compared with male patients with an HST graft (0.592 ± 0.49 N·m/kg vs 0.937 ± 0.35 N·m/kg; Cohen d [95% CI]= 0.88 [0.45, 1.31]). There were significant main effects for graft type with knee flexion ( P = .001) and extension ( P = .008) symmetry. Patients with a BPTB graft demonstrated lower knee extensor symmetry (65.7% ± 17.0%) and greater knee flexor symmetry (98.7% ± 18.0%) compared with patients with an HST graft (extension: 77.1% ± 32%, Cohen d [95% CI] = 0.47 [0.16, 0.79]; flexion: 82.9% ± 33.3%, Cohen d [95% CI] = 0.63 [0.31, 0.95]). We also observed a significant main effect for sex ( P = .028) and graft type ( P = .048) for mass-normalized knee extensor strength. Female participants and patients of either sex with BPTB grafts had lower knee extensor strength compared with male participants and patients with HST grafts, respectively. Conclusion: At approximately 6 months after ACLR, female patients reconstructed with HST autografts demonstrated weaker HST strength compared with female patients with a BPTB autograft. There were no differences in HST strength between graft types in male patients. Female patients appear to be recovering HST strength differently than male patients when using an HST autograft. These findings may have implications in surgical planning, postoperative rehabilitation, and return-to-sport decision making.
Inconsistencies in the MRI Evaluation of Supraspinatus Volume After Repair
Authors: Jang Young Hoon , Suh Bo-Kyung , Jeong Hyunseok , Kwon Oh Hyo , Kim Sae Hoon 
Published: June 2020

Background: Reversibility of rotator cuff atrophy after surgical repair is controversial. Traditionally, the cross-sectional area (CSA) of the rotator cuff was measured in conventional Y-view (CYV) via magnetic resonance imaging (MRI) to evaluate reversibility. However, it has been suggested that scanning axis inconsistency in CYV was overlooked and that the CSA in CYV reflects not only atrophy but also rotator cuff retraction. Hypothesis: Discrepancies between scanning axes in CYV cause significant errors when one is evaluating changes in the CSA of the supraspinatus (SS) using preoperative and postoperative MRI scans. A more medial section than the Y-view is not influenced as much by retraction recovery after repair. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: The study included 36 patients with full-thickness SS tear and retraction who underwent arthroscopic complete repair with preoperative MRI and immediate postoperative MRI (within 5 days after rotator cuff repair). Angles between CYV planes in the preoperative and immediate postoperative MRI scans were measured. MRI scans were reconstructed perpendicular to the scapular axes by multiplanar reconstruction. Differences between the CSAs of the SS in preoperative and postoperative Y-view on the original and reconstructed MRI scans were compared, and changes in CSAs of the SS muscles after repair in 2 sections medial to the reconstructed Y-view (RYV) were compared. Results: The mean angle between CYV planes in preoperative and postoperative MRI scans was 13.1° ± 7.1°. Mean pre- to postoperative increase in the CSA of the SS was greater in CYV than in RYV (95 ± 72 vs 75 ± 62 mm2; P = .024). Furthermore, pre- to postoperative CSA differences in the 2 medial sections were less than in RYV. For the most medial section, crossing the omohyoid origin, the CSA differences were not significant (434 ± 98 vs 448 ± 98 mm2; P = .061). Conclusion: Scanning axes inconsistencies in CYV cause unacceptable errors in CSA measurements of the SS after repair. We recommend reconstruction along a consistent axis by multiplanar reconstruction when evaluating postoperative changes in SS atrophy and the use of sections more medial than the scapular Y-view to reduce errors caused by tendon retraction.
Perceptual Evaluation of Signal-to-Noise-Ratio-Aware Dynamic Range Compression in Hearing Aids
Authors: Kowalewski Borys , Dau Torsten , May Tobias 
Published: June 2020

Dynamic range compression is a compensation strategy commonly used in modern hearing aids. Fast-acting systems respond relatively quickly to the fluctuations in the input level. This allows for more effective compression of the dynamic range of speech and hence enhanced the audibility of its low-intensity components. However, such processing also amplifies the background noise, distorts the modulation spectra of both the speech and the background, and can reduce the output signal-to-noise ratio (SNR). Recently, May et al. proposed a novel SNR-aware compression strategy, in which the compression speed is adapted depending on whether speech is present or absent. Fast-acting compression is applied to speech-dominated time–frequency (T-F) units, while noise-dominated T-F units are processed using slow-acting compression. It has been shown that this strategy provides a similar effective compression of the speech dynamic range as conventional fast-acting compression, while introducing fewer distortions of the modulation spectrum of the background and providing an improved output SNR. In this study, this SNR-aware compression strategy was compared with conventional fast- and slow-acting compression in terms of speech intelligibility and subjective preference in a group of 17 hearing-impaired listeners with varying degree of hearing loss. The results show a speech intelligibility benefit of the SNR-aware compression strategy over the conventional slow-acting system. Furthermore, the SNR-aware approach demonstrates an increased subjective preference compared with both conventional fast- and slow-acting systems.
The Effects of a Multicomponent Lower Extremity Training Technique on Physical Function in Healthy Older Adults: A Randomized Controlled Trial
Authors: Jung Hungu , Miki Yumiko , Tanaka Ryo , Yamasaki Masahiro 
Published: June 2020

Objective: We aimed to examine the outcomes of our novel multicomponent lower extremity training (MLT) technique on physical function in older adults. Methods: Participants were randomly divided into a training group (TG) or a control group (CG). The TG (4 men, 14 women) received MLT for 24 weeks, once per week. MLT contains strength, balance, and flexibility components. The CG (5 men, 10 women) did not receive any training for 24 weeks. Nine lower extremity range of motions (ROMs; hip flexion, hip abduction, hip adduction, hip extension, internal and external hip rotations, knee flexion, ankle dorsiflexion, and ankle plantar flexion) and two muscle strength assessments (knee extension and flexion) were collected. Physical performance tests were also performed, including the functional reach test, timed up and go test (TUGT), and five times sit-to-stand test (FTSST). Results: After 24 weeks, significant increases were observed in the TG in all ROMs (with the exception of knee flexion), knee extension strength, and performance in the TUGT and FTSST. Conclusions: MLT significantly improved ROM, muscle strength, and physical performance in healthy older adults. We suggest that it is an efficacious intervention in the maintenance and improvement of mobility and functional independence in healthy older adults. Trial registration: UMIN CTR, UMIN000037463. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000041955
Nursing Skills Video Selfies: An Innovative Teaching and Learning Strategy for Undergraduate Nursing Students to Master Psychomotor Skills
Authors: Sterling-Fox Cynthia , Smith Julius P. , Gariando Ophalyn , Charles Pamela 
Published: June 2020

Introduction The quality of care for patients is linked to the performance and competence of nurses. Nurse educators are challenged to prepare graduates to deliver safe, competent, patient-centered care. Nursing skills video “selfie” is an innovative teaching and learning strategy in which nursing students use technology to create videos of themselves (video selfie) performing psychomotor skills. Method The instructional exercise of creating the video selfie was administered to a group of nursing students in a medical–surgical class. The laboratory instructors identified three psychomotor nursing skills. In the skills lab, the instructors showed videos to demonstrate how the skills were performed. The students returned demonstration in the lab and were asked to return to the lab independently to practice the skills and to create a video selfie. Results The exercise encouraged students to increase the quality and length of practice and master the skill. Students demonstrated confidence to perform the skills and to accurately list each step required to perform the skills. The video selfie was used as a peer evaluation tool and as a faculty assessment tool to guide individual students’ instruction, learning, and remediation. Conclusion The exercise had some shortcomings. Future quantitative research using survey instruments to collect data from a larger group of nursing students is needed to validate the utility of this innovative teaching and learning strategy in nursing programs.
Coping profiles and health outcomes among individuals with systemic sclerosis: A latent profile analysis approach
Authors: Condon Shelley E , Roesch Scott C , Clements Philip J , Furst Daniel E , Weisman Michael H , Malcarne Vanessa L 
Published: June 2020

Background: Systemic sclerosis has negative implications for quality of life, and coping is a mechanism by which individuals can adapt more successfully to illness. This study (1) identified coping profiles in patients with systemic sclerosis and (2) examined distress and disability correlates of the profiles. Methods: A sample of 93 patients with confirmed diagnoses of systemic sclerosis received clinical examinations and reported on coping, psychological distress, and health-related disability. Latent profile analysis was used to identify coping-based profile groups. The profile groups were then compared on psychological distress and health-related disability, controlling for disease severity. Results: A two-profile solution was supported: Active Copers emphasized problem-focused, social support, counting blessings, and religious approaches to coping with systemic sclerosis. Passive Copers emphasized blaming self and others, avoidance, and wishful thinking approaches to coping. Active Copers reported significantly less psychological distress than Passive Copers, but no significant differences were found for health-related disability. Discussion: The findings identify multidimensional patterns of coping that are differentially related to psychological distress in systemic sclerosis patients. These findings can inform coping-based interventions for patients with systemic sclerosis.
Association of aberrantASNSimprinting with asparaginase sensitivity and chromosomal abnormality in childhood BCP-ALL
Authors: Watanabe Atsushi , Miyake Kunio , Nordlund Jessica , Syvänen Ann-Christine , van der Weyden Louise , Honda Hiroaki , Yamasaki Norimasa , Nagamachi Akiko , Inaba Toshiya , Ikawa Tomokatsu , Urayama Kevin Y. , Kiyokawa Nobutaka , Ohara Akira , Kimura Shunsuke , Kubota Yasuo , Takita Junko , Goto Hiroaki , Sakaguchi Kimiyoshi , Minegishi Masayoshi , Iwamoto Shotaro , Shinohara Tamao , Kagami Keiko , Abe Masako , Akahane Koshi , Goi Kumiko , Sugita Kanji , Inukai Takeshi 
Published: June 2020

AbstractKaryotype is an important prognostic factor in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL), but the underlying pharmacogenomics remain unknown. Asparaginase is an integral component in current chemotherapy for childhood BCP-ALL. Asparaginase therapy depletes serum asparagine. Normal hematopoietic cells can produce asparagine by asparagine synthetase (ASNS) activity, but ALL cells are unable to synthesize adequate amounts of asparagine. The ASNS gene has a typical CpG island in its promoter. Thus, methylation of the ASNS CpG island could be one of the epigenetic mechanisms for ASNS gene silencing in BCP-ALL. To gain deep insights into the pharmacogenomics of asparaginase therapy, we investigated the association of ASNS methylation status with asparaginase sensitivity. The ASNS CpG island is largely unmethylated in normal hematopoietic cells, but it is allele-specifically methylated in BCP-ALL cells. The ASNS gene is located at 7q21, an evolutionally conserved imprinted gene cluster. ASNS methylation in childhood BCP-ALL is associated with an aberrant methylation of the imprinted gene cluster at 7q21. Aberrant methylation of mouse Asns and a syntenic imprinted gene cluster is also confirmed in leukemic spleen samples from ETV6-RUNX1 knockin mice. In 3 childhood BCP-ALL cohorts, ASNS is highly methylated in BCP-ALL patients with favorable karyotypes but is mostly unmethylated in BCP-ALL patients with poor prognostic karyotypes. Higher ASNS methylation is associated with higher L-asparaginase sensitivity in BCP-ALL through lower ASNS gene and protein expression levels. These observations demonstrate that silencing of the ASNS gene as a result of aberrant imprinting is a pharmacogenetic mechanism for the leukemia-specific activity of asparaginase therapy in BCP-ALL.
Hematopoietic stem cells acquire survival advantage by loss of RUNX1 methylation identified in familial leukemia
Authors: Matsumura Takayoshi , Nakamura-Ishizu Ayako , Muddineni Siva Sai Naga Anurag , Tan Darren Qiancheng , Wang Chelsia Qiuxia , Tokunaga Kenji , Tirado-Magallanes Roberto , Sian Stephanie , Benoukraf Touati , Okuda Tsukasa , Asou Norio , Matsuoka Masao , Osato Motomi , Suda Toshio 
Published: June 2020

Abstract
RUNX1 is among the most frequently mutated genes in human leukemia, and the loss or dominant-negative suppression of RUNX1 function is found in myelodysplastic syndrome and acute myeloid leukemia (AML). How posttranslational modifications (PTMs) of RUNX1 affect its in vivo function, however, and whether PTM dysregulation of RUNX1 can cause leukemia are largely unknown. We performed targeted deep sequencing on a family with 3 occurrences of AML and identified a novel RUNX1 mutation, R237K. The mutated R237 residue is a methylation site by protein arginine methyltransferase 1, and loss of methylation reportedly impairs the transcriptional activity of RUNX1 in vitro. To explore the biologic significance of RUNX1 methylation in vivo, we used RUNX1 R233K/R237K double-mutant mice, in which 2 arginine-to-lysine mutations precluded RUNX1 methylation. Genetic ablation of RUNX1 methylation led to loss of quiescence and expansion of hematopoietic stem cells (HSCs), and it changed the genomic and epigenomic signatures of phenotypic HSCs to a poised progenitor state. Furthermore, loss of RUNX1 R233/R237 methylation suppressed endoplasmic reticulum stress–induced unfolded protein response genes, including Atf4, Ddit3, and Gadd34; the radiation-induced p53 downstream genes Bbc3, Pmaip1, and Cdkn1a; and subsequent apoptosis in HSCs. Mechanistically, activating transcription factor 4 was identified as a direct transcriptional target of RUNX1. Collectively, defects in RUNX1 methylation in HSCs confer resistance to apoptosis and survival advantage under stress conditions, a hallmark of a preleukemic clone that may predispose affected individuals to leukemia. Our study will lead to a better understanding of how dysregulation of PTMs can contribute to leukemogenesis.
Mutational and phenotypic characterization of hereditary hemorrhagic telangiectasia
Authors: Shovlin Claire L. , Simeoni Ilenia , Downes Kate , Frazer Zoe C. , Megy Karyn , Bernabeu-Herrero Maria E. , Shurr Abigail , Brimley Jennifer , Patel Dilipkumar , Kell Loren , Stephens Jonathan , Turbin Isobel G. , Aldred Micheala A. , Penkett Christopher J. , Ouwehand Willem H. , Jovine Luca , Turro Ernest 
Published: June 2020

Abstract
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplasia. Care delivery for HHT patients is impeded by the need for laborious, repeated phenotyping and gaps in knowledge regarding the relationships between causal DNA variants in ENG, ACVRL1, SMAD4 and GDF2, and clinical manifestations. To address this, we analyzed DNA samples from 183 previously uncharacterized, unrelated HHT and suspected HHT cases using the ThromboGenomics high-throughput sequencing platform. We identified 127 rare variants across 168 heterozygous genotypes. Applying modified American College of Medical Genetics and Genomics Guidelines, 106 variants were classified as pathogenic/likely pathogenic and 21 as nonpathogenic (variant of uncertain significance/benign). Unlike the protein products of ACVRL1 and SMAD4, the extracellular ENG amino acids are not strongly conserved. Our inferences of the functional consequences of causal variants in ENG were therefore informed by the crystal structure of endoglin. We then compared the accuracy of predictions of the causal gene blinded to the genetic data using 2 approaches: subjective clinical predictions and statistical predictions based on 8 Human Phenotype Ontology terms. Both approaches had some predictive power, but they were insufficiently accurate to be used clinically, without genetic testing. The distributions of red cell indices differed by causal gene but not sufficiently for clinical use in isolation from genetic data. We conclude that parallel sequencing of the 4 known HHT genes, multidisciplinary team review of variant calls in the context of detailed clinical information, and statistical and structural modeling improve the prognostication and treatment of HHT.
PAR4 activation involves extracellular loop 3 and transmembrane residue Thr153
Authors: Han Xu , Hofmann Lukas , de la Fuente Maria , Alexander Nathan , Palczewski Krzysztof ,   the INVENT Consortium, Nieman Marvin T. 
Published: June 2020

AbstractProtease-activated receptor 4 (PAR4) mediates sustained thrombin signaling in platelets and is required for a stable thrombus. PAR4 is activated by proteolysis of the N terminus to expose a tethered ligand. The structural basis for PAR4 activation and the location of its ligand binding site (LBS) are unknown. Using hydrogen/deuterium exchange (H/D exchange), computational modeling, and signaling studies, we determined the molecular mechanism for tethered ligand–mediated PAR4 activation. H/D exchange identified that the LBS is composed of transmembrane 3 (TM3) domain and TM7. Unbiased computational modeling further predicted an interaction between Gly48 from the tethered ligand and Thr153 from the LBS. Mutating Thr153 significantly decreased PAR4 signaling. H/D exchange and modeling also showed that extracellular loop 3 (ECL3) serves as a gatekeeper for the interaction between the tethered ligand and LBS. A naturally occurring sequence variant (P310L, rs2227376) and 2 experimental mutations (S311A and P312L) determined that the rigidity conferred by prolines in ECL3 are essential for PAR4 activation. Finally, we examined the role of the polymorphism at position 310 in venous thromboembolism (VTE) using the International Network Against Venous Thrombosis (INVENT) consortium multi-ancestry genome-wide association study (GWAS) meta-analysis. Individuals with the PAR4 Leu310 allele had a 15% reduction in relative risk for VTE (odds ratio, 0.85; 95% confidence interval, 0.77-0.94) compared with the Pro310 allele. These data are consistent with our H/D exchange, molecular modeling, and signaling studies. In conclusion, we have uncovered the structural basis for PAR4 activation and identified a previously unrecognized role for PAR4 in VTE.
Monoclonal immunoglobulins promote bone loss in multiple myeloma
Authors: Westhrin Marita , Kovcic Vlado , Zhang Zejian , Moen Siv H. , Nedal Tonje Marie Vikene , Bondt Albert , Holst Stephanie , Misund Kristine , Buene Glenn , Sundan Anders , Waage Anders , Slørdahl Tobias S. , Wuhrer Manfred , Standal Therese 
Published: June 2020

Abstract
Most patients with multiple myeloma develop a severe osteolytic bone disease. The myeloma cells secrete immunoglobulins, and the presence of monoclonal immunoglobulins in the patient’s sera is an important diagnostic criterion. Here, we show that immunoglobulins isolated from myeloma patients with bone disease promote osteoclast differentiation when added to human preosteoclasts in vitro, whereas immunoglobulins from patients without bone disease do not. This effect was primarily mediated by immune complexes or aggregates. The function and aggregation behavior of immunoglobulins are partly determined by differential glycosylation of the immunoglobulin-Fc part. Glycosylation analyses revealed that patients with bone disease had significantly less galactose on immunoglobulin G (IgG) compared with patients without bone disease and also less sialic acid on IgG compared with healthy persons. Importantly, we also observed a significant reduction of IgG sialylation in serum of patients upon onset of bone disease. In the 5TGM1 mouse myeloma model, we found decreased numbers of lesions and decreased CTX-1 levels, a marker for osteoclast activity, in mice treated with a sialic acid precursor, N-acetylmannosamine (ManNAc). ManNAc treatment increased IgG-Fc sialylation in the mice. Our data support that deglycosylated immunoglobulins promote bone loss in multiple myeloma and that altering IgG glycosylation may be a therapeutic strategy to reduce bone loss.