bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Relationships Between 25-Hydroxyvitamin D and Echocardiographic Parameters in Female Basketball Players
Authors: Radovanović Dragan , Stoičkov Viktor , Pechanova Olga , Scanlan Aaron T. , Jakovljević Vladimir , Stojanović Emilija 
Published: May 2022

Objective:
This study was undertaken to (1) describe the cardiac structure and function and (2) to quantify the relationships between 25-hydroxyvitamin D [25(OH)D] and echocardiographic parameters in female basketball players.

Design:
A cross-sectional experimental design.

Setting:
Controlled laboratory setting.

Participants:
Professional, female basketball players (n = 18).

Intervention:
25(OH)D and echocardiographic screening at the midpoint of the in-season phase, over a 2-week period in late Fall.

Main Outcome Measures:
25(OH)D and echocardiographic parameters.

Results:
A high prevalence of vitamin D insufficiency was observed in the female players examined (77.8%), with most also displaying eccentric cardiac hypertrophy (77.8%). Nonsignificant, moderate correlations were found between 25(OH)D and structural echocardiographic parameters, including left atrium diameter (r = 0.34, P = 0.16), left ventricular (LV) end-systolic diameter (r = −0.46, P = 0.06), posterior wall thickness (r = 0.36, P = 0.14), LV mass (r = 0.30, P = 0.23), and LV index (r = 0.33, P = 0.18). Significant, large correlations were found between 25(OH)D and echocardiographic parameters indicative of systolic function, including LV ejection fraction (r = 0.59, P = 0.01), fractional shortening (r = 0.59, P = 0.01), and peak systolic mitral tissue velocity (r = 0.51, P = 0.003). Similarly, a significant, large correlation was found between 25(OH)D and diastolic function as indicated by mitral valve inflow deceleration time (r = 0.51, P = 0.03).

Conclusions:
Our findings suggest the importance of female basketball players maintaining 25(OH)D concentration, given its possible physiological benefits on cardiac structure and function.
Presenting Symptoms and Diagnosis of Vulvar Lichen Sclerosus in Premenopausal Women: A Cross-Sectional Study
Authors: Krapf Jill M. , Smith Alyssa B. , Cigna Sarah T. , Goldstein Andrew T. 
Published: May 2022

Objectives/Purpose
Presenting symptoms of vulvar lichen sclerosus (LS) specific to premenopausal women are not well reported in the literature and may differ from those in postmenopausal women. This study aimed to characterize the presentation of vulvar LS among premenopausal women.

Materials and Methods
An observational web-based study was conducted in premenopausal women with biopsy-confirmed vulvar LS between the ages of 18–50 years. Participants completed a 28-question survey evaluating characteristics of symptoms, timing of diagnosis, alternate diagnoses, and presence of concomitant autoimmune conditions.

Results
Of the 956 responses received, 503 met inclusion criteria of biopsy-confirmed LS and premenopausal status. Average age of symptom onset was 27 years, and average age of diagnosis was 32 years, with a 4-year delay in diagnosis. Symptoms most present were dyspareunia (68%) and tearing with intercourse or vaginal insertion (63%). Symptoms that affect the individual most were also dyspareunia (44%) and tearing with intercourse or vaginal insertion (39%). Symptoms that most frequently prompted patients to seek medical attention were dyspareunia (35%), pruritus (31%) and tearing with intercourse or vaginal insertion (26%). Most common skin changes included hypopigmentation (81%), vulvar fissures (72%), and labial resorption (60%), with fissures affecting the individual the most (48%). Sixty-six percent of the respondents initially received an alternative diagnosis, most commonly vulvovaginal yeast infection (49%). Hypothyroidism was the most common concurrent autoimmune condition (10%).

Conclusions
Vulvar LS affects premenopausal women, commonly presenting with dyspareunia and tearing with intercourse. This condition should be considered and evaluated in premenopausal women presenting with vulvar symptoms and sexual pain.
Effects of Generic Exchange of Levodopa Medication in Patients With Parkinson Disease
Authors: Weitzel Johanna , Langer Klaus , Rose Olaf 
Published: May 2022

Objectives
Generic exchange is common practice in most healthcare systems. This study investigated how patients with Parkinson disease (PD) perceived a switch of their levodopa medication and the resulting effects on their PD symptoms.

Methods
A questionnaire was developed, piloted, and finally distributed to 13,857 members of the national PD patient support group. It was designed to be completed by patients and their pharmacies. χ2 tests for independence statistics with or without Monte Carlo simulation were performed. Cramér φ and Cramér V were calculated. McNemar test was used to investigate whether a generic switch of a levodopa-containing medication had an impact on PD symptoms.

Results
Analyses were done with 410 finalized respondents of 13,857 distributed questionnaires. More than half of the responders were 75 years or older and rated themselves Hoehn and Yahr stages 3 to 5. Most patients were confused by a change of their medication. A total of 54.7% of the switchers (n = 148) reported swallowing difficulties with medication, which was significantly more frequent than with nonswitchers (37.3% of 204, P = 0.001). Adverse effects related to the switch were reported by 26.6% of all switchers (switchback rate, 20.5%). The patients at higher Hoehn and Yahr stages were affected to a greater extend.

Conclusions
Patients, who experienced any brand switch of their levodopa medication, frequently expressed distrust and confusion. Swallowing difficulties and negative effects on their symptoms were problems, which were more pronounced in advanced disease stages. It remains unclear whether the detrimental impact on therapy was caused by the brand switch or by a nocebo effect.
The Impact of a 22-Month Multistep Implementation Program on Speaking-Up Behavior in an Academic Anesthesia Department
Authors: Walther Fabio , Schick Carl , Schwappach David , Kornilov Evgeniya , Orbach-Zinger Sharon , Katz Daniel , Heesen Michael 
Published: May 2022

Background
Speaking-up is a method of assertive communication that increases patient safety but often encounters barriers. Numerous studies describe programs introducing speaking-up with varying success; the common denominator seems to be the need for a multimodal and sustained approach to achieve the required change in behavior and culture for safer health care.

Methods
Before implementing a 22-month multistep program for establishing and strengthening speaking-up at our institution, we assessed perceived safety culture using the “Safety Attitudes Questionnaire.” After program completion, participants completed parts of the same Safety Attitudes Questionnaire relevant to speaking-up, and preresult and postresult were compared. In addition, levels of speaking-up and assertive communication were compared with a Swiss benchmark using results from the “Speaking-up About Patient Safety Questionnaire.”

Results
Safety Attitudes Questionnaire scores were significantly higher after program completion in 2 of 3 answered questions (median [first quartile, third quartile), 5.0 [4.0, 5.0] versus 4.0 [4.0, 5.0], P = 0.0002, and 5.0 [4.0, 5.0] versus 4.0 [4.0, 4.0] P = 0.002; n = 34). Our composite score on the Speaking-up About Patient Safety Questionnaire was significantly higher (mean ± SD, 5.9 ± 0.7 versus 5.2 ± 1.0;P < 0.001) than the benchmark (n = 65).

Conclusions
A long-term multimodal program for speaking-up was successfully implemented. Attitude and climate toward safety generally improved, and postprogram perceived levels of assertive communication and speaking-up were higher than the benchmark. These results support current opinion that multimodal programs and continued effort are required, but that speaking-up can indeed be strengthened.
A Longitudinal Evaluation of Computed Tomography Radiation Incidents Within a Multisite NHS Trust
Authors: Adamson Helen Katie , Foster Beverley , Clarke Ruth , Scally Andrew , Snaith Beverly 
Published: May 2022

Objectives
This single-center review explores trends in computed tomography “radiation incidents” and suggests strategies for improvement.

Method
A retrospective mixed-methods approach was used in this longitudinal evaluation of radiation incidents within a multisite NHS Trust in northern England. DATIX was interrogated at the Trust level to identify all records linked to radiation incident in computed tomography departments between January 1, 2015, and December 31, 2018.

Results
During the 4-year review period, 159,596 exams were performed at the Trust and a total of 133 incidents were recorded. This comprised 42.1% (n = 56) of radiation incidents, 43.6% (n = 58) of near-miss incidents, and 14.3% (n = 19) of repeat scans due to extravasation of contrast. The reported radiation incident rate was 0.08%. These data suggest an approximation of 1 incident per thousand cases. Most incidents were investigated using a “system approach,” and the reports highlighted the relevant action that had been taken to try and prevent recurrence of the incident. Qualitative data collected from the root cause analysis minutes demonstrated themes related to the contributory factors, incident analysis performed, and overall learning.

Conclusions
Computed tomography departments need to focus on a system approach instead of the “person approach” to identify areas where efficiencies can be implemented. Staff should feel open to discuss system inefficiencies that they experience and may highlight problems the management is unaware of. The reporting of all types of incidents, including near misses, should be encouraged, to foster an open culture and to expand learning.
The Stoplight Mobility Alert System for Safety and Prevention of Falls in Children With Physical and Cognitive Impairments
Authors: Mullen Joellan B. , Wirt Steven Z. , Moser Alana , Niedzwecki Christian 
Published: May 2022

Objective(s)
This study aimed to decrease the rate of falls in children with cognitive and physical impairments on a pediatric acute inpatient rehabilitation unit (IRU) using a novel tool, the Stoplight Mobility Alert System (SMAS).

Methods
We conducted a pilot, prospective, quality improvement study in an 8-bed (increased to 12 beds; October 1, 2019) acute inpatient pediatric IRU at a level 1 trauma center. All patients admitted between October 1, 2012, and October 1, 2020, were included as participants. Interventions used were as follows: (1) SMAS, a colored alert system placed on door slides and in-room for visual cues (red, assistance/hands on; yellow, supervision/eyes on; green, independent/hands off), and (2) handouts and one-on-one education for staff and patients/families. Main outcome measures included fall rate on the IRU.

Results
Using the SMAS, the total fall rate decreased from 10.78 to 4.36 falls per 1000 patient-days. Longitudinally, the intrinsic fall rate decreased from 8.36 to 5.60 falls per 1000 patient-days, and the extrinsic fall rate decreased from 4.56 to 1.36 falls per 1000 patient-days.

Conclusions
The implementation of the SMAS is effective in decreasing total, intrinsic, and extrinsic fall rates in an acute pediatric inpatient rehabilitation program both acutely and longitudinally.
The impact of ankle-foot orthosis's plantarflexion resistance on knee adduction moment in people with chronic stroke
Authors: Kobayashi Toshiki , Hunt Grace , Orendurff Michael S. , Gao Fan , Singer Madeline L. , Foreman K. Bo 
Published: May 2022

Background:
An ankle-foot orthosis (AFO) is used to assist gait of people with chronic stroke. It is widely accepted that AFO’s plantarflexion resistance affects sagittal knee moments during their gait. However, its effect on the coronal knee moment remains unclear. This study aimed to examine the effects of varying articulated AFO’s plantarflexion resistance on knee adduction moment in people with chronic stroke.

Methods:
Ten people with chronic stroke participated in this study. Gait performance was measured using a Vicon 3-dimensional motion capture system and a Bertec split-belt instrumented treadmill. The participants walked on the treadmill wearing an articulated AFO whose plantarflexion resistance could be systematically adjusted. The ankle joints were set to four distinct levels of plantarflexion resistance (S1 < S2 < S3 < S4). The coronal ankle and knee joint moment, center of pressure, and ground reaction force were analyzed using Visual3D.

Results:
The external knee adduction moment increased significantly (P < .001) and the position of the center of pressure trajectory shifted significantly (P = .003) in the medial direction as the plantarflexion resistance of the AFO was increased from the least resistive condition (S1) to the most resistive condition (S4). The maximum knee adduction moment (median [interquartile range]) was S1: 0.097 (−0.012 to 0.265) Nm/kg; S2: 0.136 (0.040 to 0.287) Nm/kg; S3: 0.160 (0.465 to 0.289) Nm/kg; and S4: 0.192 (0.080 to 0.288) Nm/kg.

Conclusions:
This study demonstrated that varying AFO’s plantarflexion resistance altered the knee adduction moment, likely by altering the center of pressure trajectory while walking, in people with chronic stroke.
A novelde novoFEM1C variant is linked to neurodevelopmental disorder with absent speech, pyramidal signs, and limb ataxia
Authors: Dubey Abhishek Anil , Krygier Magdalena , Szulc Natalia A. , Rutkowska Karolina , Kosińska Joanna , Pollak Agnieszka , Rydzanicz Małgorzata , Kmieć Tomasz , Mazurkiewicz-Bełdzińska Maria , Pokrzywa Wojciech , Płoski Rafał 
Published: May 2022

AbstractThe principal component of the protein homeostasis network is the ubiquitin-proteasome system. Ubiquitination is mediated by an enzymatic cascade involving, i.e., E3 ubiquitin ligases, many of which belong to the cullin-RING ligases family. Genetic defects in the ubiquitin-proteasome system components, including cullin-RING ligases, are known causes of neurodevelopmental disorders. Using exome sequencing to diagnose a pediatric patient with developmental delay, pyramidal signs, and limb ataxia, we identified ade novomissense variant c.376G>C; p.(Asp126His) in theFEM1Cgene encoding a cullin-RING ligase substrate receptor. This variant alters a conserved amino acid located within a highly constrained coding region and is predicted as pathogenic by mostin silicotools. In addition, ade novo FEM1Cmutation of the same residue p.(Asp126Val) was associated with an undiagnosed developmental disorder, and the relevant variant (FEM1CAsp126Ala) was found to be functionally compromisedin vitro. Our computational analysis showed that FEM1CAsp126Hishampers protein substrate binding. To further assess its pathogenicity, we used the nematodeCaenorhabditis elegans. We found that the FEM-1Asp133Hisanimals (expressing variant homologous to theFEM1Cp.(Asp126Val)) had normal muscle architecture yet impaired mobility. Mutant worms were sensitive to the acetylcholinesterase inhibitor aldicarb but not levamisole (acetylcholine receptor agonist), showing that their disabled locomotion is caused by synaptic abnormalities and not muscle dysfunction. In conclusion, we provide the first evidence from an animal model suggesting that a mutation in the evolutionarily conserved FEM1C Asp126 position causes a neurodevelopmental disorder in humans.
Integrative analysis of the 3D genome and epigenome in mouse embryonic tissues
Authors: Yu Miao , Zemke Nathan R. , Chen Ziyin , Juric Ivan , Hu Rong , Raviram Ramya , Abnousi Armen , Fang Rongxin , Zhang Yanxiao , Gorkin David U. , Li Yang , Zhao Yuan , Lee Lindsay , Schmitt Anthony D. , Qiu Yunjiang , Dickel Diane E. , Visel Axel , Pennacchio Len A. , Hu Ming , Ren Bing 
Published: May 2022

AbstractWhile a rich set of putative cis-regulatory sequences involved in mouse fetal development has been annotated recently based on chromatin accessibility and histone modification patterns, delineating their role in developmentally regulated gene expression continues to be challenging. To fill this gap, we mapped chromatin contacts between gene promoters and distal sequences genome-wide in seven mouse fetal tissues, and for one of them, across six developmental stages. We identified 248,620 long-range chromatin interactions centered at 14,138 protein-coding genes and characterized their tissue-to-tissue variations as well as developmental dynamics. Integrative analysis of the interactome with previous epigenome and transcriptome datasets from the same tissues revealed a strong correlation between the chromatin contacts and chromatin state at distal enhancers, as well as gene expression patterns at predicted target genes. We predicted target genes of 15,098 candidate enhancers, and used them to annotate target genes of homologous candidate enhancers in the human genome that harbor risk variants of human diseases. We present evidence that schizophrenia and other adult disease risk variants are frequently found in fetal enhancers, providing support for the hypothesis of fetal origins of adult diseases.
Ongoing Replication Stress Response and New Clonal T Cell Development Discriminate Between Liver and Lung Recurrence Sites and Patient Outcomes in Pancreatic Ductal Adenocarcinoma
Authors: Link Jason M. , Pelz Carl , Worth Patrick J. , Owen Sydney , Keith Dove , Langer Ellen M. , Grossblatt-Wait Alison , Creason Allison L. , Egger Julian , Holly Hannah , English Isabel , MacPherson Kevin , Tsuda Motoyuki , Goecks Jeremy , Demir Emek , Kardosh Adel , Lopez Charles D. , Sheppard Brett C. , Guimaraes Alex , Brinkerhoff Brian , Morgan Terry K. , Mills Gordon , Brody Jonathan , Sears Rosalie C. 
Published: May 2022

AbstractBackground and AimsMetastatic pancreatic adenocarcinoma (mPDAC) is lethal, yet a subset of patients who have metastatic disease that spreads only to the lung have better outcomes. We identified unique transcriptomic and immune features that distinguish patients who develop metastases in the liver (liver cohort) versus those with lung-avid but liver-averse mPDAC (lung cohort).MethodsWe used clinical data from the Oregon Pancreas Tissue Registry to identify PDAC patients with liver and/or lung metastases. Gene expression and genomic alteration data from 290 PDAC tumors were used to identify features unique to patients from the liver and lung cohorts. In parallel, T cell receptor sequencing data from 289 patients were used to identify immune features unique to patients in the lung cohort.ResultsLung cohort patients had better survival outcomes than liver cohort patients. Primary tumors from patients in the liver cohort expressed a novel gene signature associated with ongoing replication stress (RS) response predictive of poor patient outcome independent from known subtypes. In contrast, patients with tumors lacking the RS response signature survived longer, especially if their tumors had alterations in DNA damage repair genes. A subset of patients in the lung cohort demonstrated new T cell clonal development in their primary and metastatic tumors leading to diverse peripheral blood TCR repertoires.ConclusionLiver-avid metastatic PDAC is associated with an ongoing RS response, whereas tumors lacking the RS response with ongoing T cell clonal responses may have unique vulnerabilities allowing long-term survival in patients with lung-avid, liver-averse metastatic PDAC.
Synovial fibroblasts assume distinct functional identities and secrete R-spondin 2 to drive osteoarthritis
Authors: Knights Alexander J. , Farrell Easton C. , Ellis Olivia M. , Lammlin Lindsey , Junginger Lucas M. , Rzeczycki Phillip M. , Bergman Rachel F. , Pervez Rida , Cruz Monique , Samani Alexa A. , Wu Chia-Lung , Hankenson Kurt D. , Maerz Tristan 
Published: May 2022

ABSTRACTObjectivesSynovium is acutely affected following joint trauma and contributes to post-traumatic osteoarthritis (PTOA) progression. Little is known about discrete cell types and molecular mechanisms in PTOA synovium. We aimed to describe synovial cell populations and their dynamics in PTOA, with a focus on fibroblasts. We also sought to define mechanisms of synovial Wnt/β-catenin signaling, given its emerging importance in arthritis.MethodsWe subjected mice to non-invasive anterior cruciate ligament rupture as a model of human joint injury. We performed single-cell RNA-sequencing to assess synovial cell populations, subjected Wnt-GFP reporter mice to joint injury to study Wnt-active cells, and performed intra-articular injections of the Wnt agonist R-spondin 2 (Rspo2) to assess whether gain-of-function induced pathologies characteristic of PTOA. Lastly, we used cultured fibroblasts, macrophages, and chondrocytes to study how Rspo2 orchestrates crosstalk between joint cell types.ResultsWe uncovered seven distinct functional subsets of synovial fibroblasts in healthy and injured synovium, and defined their temporal dynamics in early and established PTOA. Wnt/β-catenin signaling was overactive in PTOA synovium, and Rspo2 was strongly induced after injury and secreted exclusively by Prg4hilining fibroblasts. Trajectory analyses predicted that Prg4hilining fibroblasts arise from a pool of Dpp4+ mesenchymal progenitors in synovium, with SOX5 identified as a potential regulator of this emergence. We also showed that Rspo2 orchestrated pathological crosstalk between synovial fibroblasts, macrophages, and chondrocytes.ConclusionsSynovial fibroblasts assume distinct functional identities during PTOA, and Prg4hilining fibroblasts secrete the Wnt agonist Rspo2 to drive pathological crosstalk in the joint after injury.
Characteristics of intestinal microflora and dysbiosis in relation to the disease duration in patients with Meniere’s disease
Authors: Mochizuki Fumihiro , Komori Manabu , Sasano Yoshiyuki , Ito Yusuke , Hoffer Michael E , Koizuka Izumi 
Published: May 2022

AbstractHypothesisDysbiosis of the intestinal microflora has been reported in stress-induced depression and irritable colitis, a similar abnormality may also occur in stress-triggered Meniere’s disease.BackgroundMeniere’s disease is an intractable disease characterized by paroxysms of intense rotatory dizziness, hearing loss, and other auditory symptoms. It is believed to be caused by endolymphatic hydrops of the vestibule and cochlea. The diagnosis of Meniere’s disease is based on the diagnostic criteria established by the Barany Society and AAO-HNS and Journal of Vestibular Research as definite or probable cases. Endolymphatic hydrops identification using cochlear contrast-enhanced MRI (hybrid of reversed image of positive endolymph signal and native image of positive perilymph signal [HYDROPS]) is an objective test for Meniere’s disease, enabling reliable diagnosis of this disease.MethodsWe investigated the gut microbiota of 10 patients (6 males and 4 females, mean age 49.6 ± 8.1 years) who met the diagnostic criteria for a unilateral definite case of Meniere’s disease using the diagnostic criteria of the Journal of Vestibular Research, and who also had significant endolymphatic hydrops on the affected side on HYDROPS. Intestinal microbiota tests were performed on these 10 patients and the results were evaluated in relation to the duration of disease, results of audiometry of the affected side, and DHI (Dizziness Handicap Inventory) score.ResultsA significant negative correlation was found between the disease duration and Shannon diversity index and Faith’s phylogenetic diversity, which indicated dysbiosis of the intestinal microflora. No correlation was found between the indicators of microbial diversity and the results of audiometry or the DHI on the affected side. Dysbiosis of the intestinal microbiota worsened with increasing duration of Meniere’s disease. Moreover,Akkermansia muciniphilawas not detected in any patient with Meniere’s disease.Conclusions.Despite the small number of cases in this study (n = 10), the findings indicate the possibility of abnormalities of the intestinal microflora in Meniere’s disease.