bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in Outpatient Opioid Prescribing During the COVID-19 Pandemic: An Interrupted Time Series Analysis
Authors: Rikin Sharon , Perez Hector R. , Zhang Chenshu , Khalid Laila , Groeger Justina , Deng Yuting , Starrels Joanna L. 
Published: February 2022

Objectives: Changes in health care delivery during the COVID-19 pandemic may have impacted opioid prescribing. This study evaluated the impact of restrictions on in-person care on opioid prescribing in the outpatient setting. The hypothesis was that after restrictions to in-person care were implemented, there would be a reduction in the number of chronic and non-chronic opioid prescriptions. Methods: An interrupted time series analysis was conducted to compare the number of weekly opioid prescriptions between baseline (1/1/2019-3/14/2020), restriction (3/15/2020-6/6/2020), and reopening (6/7/2020-10/31/2020) periods at outpatient practices within a health system in Bronx, NY. Analyses were stratified by prescription type (chronic if the patient had been prescribed opioids for >90 days, or non-chronic). Results: For chronic opioid prescriptions, the week restrictions were implemented, there was an increase in the number of prescriptions compared to what was predicted if there had been no interruption (34.8 prescriptions, 95% CI: 8.0, 61.7). Subsequently, the weekly trend in prescribing was not different in the restriction period or in the reopening period compared to the previous time periods. For non-chronic opioid prescriptions, during the restriction period, the weekly trend in prescribing decreased compared to baseline (−5.0 prescriptions/week, 95% CI: −9.0, −1.0). Subsequently, during the reopening period, the weekly trend in prescribing increased compared to the restriction period (6.4 prescriptions/week, 95% CI: 2.2, 10.7). Conclusions: Despite abrupt restrictions on in-person care, chronic opioid prescriptions did not decrease, which is evidence that providers evolved to meet patient needs. Changes in non-chronic prescriptions are likely related to patients electing not to pursue care for acute pain or challenges with appointment availability.
COVID-19 Patients’ Satisfaction Levels with Nursing Care: A Cross-Sectional Study
Authors: Alhowaymel Fahad , Abaoud Abdulaziz , Alhuwaimel Abdullah , Alenezi Atallah , Alsayed Nahed 
Published: February 2022

Introduction COVID-19 is the most recent coronavirus diseases that was first identified in December 2019 and began its exponential spread globally. The critical role of nurses can be severely impacted during pandemics such as COVID-19 when the world is less prepared. Objective To investigate and measure COVID-19 patients’ satisfaction levels with the quality of nursing care provided in the Riyadh Province of Saudi Arabia. Methods The study used a cross-sectional questionnaire to collect data from COVID-19 patients who were hospitalized or quarantined for at least 48 h or more. The study utilized the Arabic version of the Patient Satisfaction with Nursing Care Quality Questionnaire (PSNCQQ-Ar) to assess patients’ satisfaction levels with nursing care. Descriptive statistics, Mann-Whitney U, and Kruskal-Wallis tests were performed to examine the objectives of the study. Results Ninety-six patients reported relatively high satisfaction levels with the overall nursing care. Patients also reported high satisfaction levels with the provided care, and the information that was provided. There were statistically significant differences in the mean score of patients satisfaction in relation to age, educational level, where patients are originally from, and patients recommendation of the hospitals. Conclusions Individual characteristics and attributes played a role in the process of evaluating nursing care services. Measuring nursing care quality clarified the significant role of nurses during the COVID-19 pandemic. This study provides valuable information that could help in identifying weaknesses and reinforcing strengths about nursing care to be fully prepared against pandemics and other health-related crises and emergencies in the future.
Single-cell transcriptional analysis of human endothelial colony-forming cells from patients with low VWF levels
Authors: Ng Christopher J. , Liu Alice , Venkataraman Sujatha , Ashworth Katrina J. , Baker Christopher D. , O’Rourke Rebecca , Vibhakar Rajeev , Jones Kenneth L. , Di Paola Jorge 
Published: February 2022

Abstract
von Willebrand factor (VWF) plays a key role in normal hemostasis, and deficiencies of VWF lead to clinically significant bleeding. We sought to identify novel modifiers of VWF levels in endothelial colony-forming cells (ECFCs) using single-cell RNA sequencing (scRNA-seq). ECFCs were isolated from patients with low VWF levels (plasma VWF antigen levels between 30 and 50 IU/dL) and from healthy controls. Human umbilical vein endothelial cells were used as an additional control cell line. Cells were characterized for their Weibel Palade body (WPB) content and VWF release. scRNA-seq of all cell lines was performed to evaluate for gene expression heterogeneity and for candidate modifiers of VWF regulation. Candidate modifiers identified by scRNA-seq were further characterized with small-interfering RNA (siRNA) experiments to evaluate for effects on VWF. We observed that ECFCs derived from patients with low VWF demonstrated alterations in baseline WPB metrics and exhibit impaired VWF release. scRNA-seq analyses of these endothelial cells revealed overall decreased VWF transcription, mosaicism of VWF expression, and genes that are differentially expressed in low VWF ECFCs and control endothelial cells (control ECs). An siRNA screen of potential VWF modifiers provided further evidence of regulatory candidates, and 1 such candidate, FLI1, alters the transcriptional activity of VWF. In conclusion, ECFCs from individuals with low VWF demonstrate alterations in their baseline VWF packaging and release compared with control ECs. scRNA-seq revealed alterations in VWF transcription, and siRNA screening identified multiple candidate regulators of VWF.
How I treat refractory/relapsed hairy cell leukemia with BRAF inhibitors
Authors: Falini Brunangelo , De Carolis Luca , Tiacci Enrico 
Published: February 2022

Abstract
Hairy cell leukemia (HCL) responds very well to frontline chemotherapy with purine analogs (cladribine and pentostatine). However, approximately half of patients experience 1 or more relapses, which become progressively resistant to these myelotoxic and immunosuppressive agents. At progression, standard therapeutic options include a second course of purine analogs alone or in combination with rituximab and, upon second relapse, therapy with the anti-CD22 immunotoxin moxetumomab pasudotox. Furthermore, blockade of the mutant BRAF-V600E kinase (the pathogenetic hallmark of HCL) through orally available specific inhibitors (vemurafenib or dabrafenib) effaces the peculiar morphologic, phenotypic, and molecular identity of this disease and its typical antiapoptotic behavior and is emerging as an attractive chemotherapy-free strategy in various clinical scenarios. These include patients with, or at risk of, severe infections and, in a highly effective combination with rituximab, patients with relapsed or refractory HCL. Other treatments explored in clinical trials are BTK inhibition with ibrutinib and co-inhibition of BRAF (through dabrafenib or vemurafenib) and its downstream target MEK (through trametinib or cobimetinib). Here, we focus on our experience with BRAF inhibitors in clinical trials and as off-label use in routine practice by presenting 3 challenging clinical cases to illustrate their management in the context of all available treatment options.
Telomeres, aging, and cancer: the big picture
Authors: Lansdorp Peter M. 
Published: February 2022

Abstract
The role of telomeres in human health and disease is yet to be fully understood. The limitations of mouse models for the study of human telomere biology and difficulties in accurately measuring the length of telomere repeats in chromosomes and cells have diverted attention from many important and relevant observations. The goal of this perspective is to summarize some of these observations and to discuss the antagonistic role of telomere loss in aging and cancer in the context of developmental biology, cell turnover, and evolution. It is proposed that both damage to DNA and replicative loss of telomeric DNA contribute to aging in humans, with the differences in leukocyte telomere length between humans being linked to the risk of developing specific diseases. These ideas are captured in the Telomere Erosion in Disposable Soma theory of aging proposed herein.
Sphingosine-1 phosphate receptor 1 contributes to central sensitization in recurrent nitroglycerin-induced chronic migraine model
Authors: Pan Qi , Wang Yunfeng , Tian Ruimin , Wen Qianwen , Qin Guangcheng , Zhang Dunke , Chen Lixue , Zhang Yixin , Zhou Jiying 
Published: February 2022

Abstract
Background
Central sensitization is an important pathophysiological mechanism of chronic migraine (CM), and microglia activation in trigeminocervical complex (TCC) contributes to the development of central sensitization. Emerging evidence implicates that blocking sphingosine-1-phosphate receptor 1 (S1PR1) can relieve the development of chronic pain and inhibit the activation of microglia. However, it is unclear whether S1PR1 is involved in the central sensitization of CM. Therefore, the purpose of this study is to explore the role of S1PR1 and its downstream signal transducers and activators of transcription 3 (STAT3) signaling pathway in the CM, mainly in inflammation.

Methods
Chronic intermittent intraperitoneal injection of nitroglycerin (NTG) established a mouse model of CM. First, we observed the changes and subcellular localization of S1PR1 in the trigeminocervical complex (TCC). Then, W146, a S1PR1 antagonist; SEW2871, a S1PR1 agonist; AG490, a STAT3 inhibitor were applied by intraperitoneal injection to investigate the related molecular mechanism. The changes in the number of microglia and the expression of calcitonin gene-related peptide (CGRP) and c-fos in the TCC site were explored by immunofluorescence. In addition, we studied the effect of S1PR1 inhibitors on STAT3 in lipopolysaccharide-treated BV-2 microglia.

Results
Our results showed that the expression of S1PR1 was increased after NTG injection and S1PR1 was colocalized with in neurons and glial cells in the TCC. The S1PR1 antagonist W146 alleviated NTG-induced hyperalgesia and suppressed the upregulation of CGRP, c-fos and pSTAT3 in the TCC. Importantly, blocking S1PR1 reduced activation of microglia. In addition, we found that inhibiting STAT3 signal also attenuated NTG-induced basal mechanical and thermal hyperalgesia.

Conclusions
Our results indicate that inhibiting S1PR1 signal could alleviate central sensitization and inhibit microglia activity caused by chronic NTG administration via STAT3 signal pathway, which provide a new clue for the clinical treatment of CM.
Micronutrient supplementation affects DNA methylation in male gonads with potential intergenerational epigenetic inheritance involving the embryonic development through glutamate receptor-associated genes
Authors: Saito Takaya , Whatmore Paul , Taylor John F. , Fernandes Jorge M. O. , Adam Anne-Catrin , Tocher Douglas R. , Espe Marit , Skjærven Kaja H. 
Published: February 2022

Abstract
Background
DNA methylation has an important role in intergenerational inheritance. An increasing number of studies have reported evidence of germline inheritance of DNA methylation induced by nutritional signals in mammals. Vitamins and minerals as micronutrients contribute to growth performance in vertebrates, including Atlantic salmon (Salmo salar), and also have a role in epigenetics as environmental factors that alter DNA methylation status. It is important to understand whether micronutrients in the paternal diet can influence the offspring through alterations of DNA methylation signatures in male germ cells.

Results
Here, we show the effect of micronutrient supplementation on DNA methylation profiles in the male gonad through a whole life cycle feeding trial of Atlantic salmon fed three graded levels of micronutrient components. Our results strongly indicate that micronutrient supplementation affects the DNA methylation status of genes associated with cell signalling, synaptic signalling, and embryonic development. In particular, it substantially affects DNA methylation status in the promoter region of a glutamate receptor gene, glutamate receptor ionotropic, NMDA 3A-like (grin3a-like), when the fish are fed both medium and high doses of micronutrients. Furthermore, two transcription factors, histone deacetylase 2 (hdac2) and a zinc finger protein, bind to the hyper-methylated site in the grin3a-like promoter. An estimated function of hdac2 together with a zinc finger indicates that grin3a-like has a potential role in intergenerational epigenetic inheritance and the regulation of embryonic development affected by paternal diet.

Conclusions
The present study demonstrates alterations of gene expression patterns and DNA methylation signatures in the male gonad when Atlantic salmon are fed different levels of micronutrients. Alterations of gene expression patterns are of great interest because the gonads are supposed to have limited metabolic activities compared to other organs, whereas alterations of DNA methylation signatures are of great importance in the field of nutritional epigenetics because the signatures affected by nutrition could be transferred to the next generation. We provide extensive data resources for future work in the context of potential intergenerational inheritance through the male germline.
Long-read sequencing of the zebrafish genome reorganizes genomic architecture
Authors: Chernyavskaya Yelena , Zhang Xiaofei , Liu Jinze , Blackburn Jessica 
Published: February 2022

Abstract
Background
Nanopore sequencing technology has revolutionized the field of genome biology with its ability to generate extra-long reads that can resolve regions of the genome that were previously inaccessible to short-read sequencing platforms. Over 50% of the zebrafish genome consists of difficult to map, highly repetitive, low complexity elements that pose inherent problems for short-read sequencers and assemblers.

Results
We used long-read nanopore sequencing to generate a de novo assembly of the zebrafish genome and compared our assembly to the current reference genome, GRCz11. The new assembly identified 1697 novel insertions and deletions over one kilobase in length and placed 106 previously unlocalized scaffolds. We also discovered additional sites of retrotransposon integration previously unreported in GRCz11 and observed the expression of these transposable elements in adult zebrafish under physiologic conditions, implying they have active mobility in the zebrafish genome and contribute to the ever-changing genomic landscape.

Conclusions
We used nanopore sequencing to improve upon and resolve the issues plaguing the current zebrafish reference assembly, GRCz11. Zebrafish is a prominent model of human disease, and our corrected assembly will be useful for studies relying on interspecies comparisons and precise linkage of genetic events to disease phenotypes.
Nationwide improvements in geriatric mortality due to traumatic brain injury in Japan
Authors: Hosomi Sanae , Sobue Tomotaka , Kitamura Tetsuhisa , Ogura Hiroshi , Shimazu Takeshi 
Published: February 2022

Abstract
Background
Traumatic brain injury (TBI), both isolated and in combination with extracranial lesions, is a global health problem associated with high mortality. Among various risk factors for poor clinical outcomes, age is the most important independent predictor of mortality in patients with TBI. TBI-related mortality is expected to increase as the society ages. However, in a super-aged society such as Japan, little is known about the trend of TBI-related mortality among older adults. Herein, we assessed the nationwide trend of the incidence and clinical outcomes of geriatric patients with TBI in Japan using the national Japanese Trauma Data Bank (JTDB) registry.

Methods
In this retrospective cohort study, cases of TBI (aged ≥65 years) in hospitals registered with the JTDB database between January 2004 and December 2018 were included. In-hospital mortality was the primary outcome, and mortality in the emergency department was the secondary outcome. The odds ratios (ORs) and 95% confidence intervals (CIs) for in-hospital deaths with respect to 3-year periods were assessed using multivariable analysis after adjusting for potential confounders.

Results
The main cause of TBI in older individuals was falls. The proportion of patients who died after hospitalization during the study period decreased markedly from 29.5% (194/657) during 2004–2006 to 14.2% (1309/9240) during 2016–2018 in the isolated TBI group (adjusted OR = 0.42, 95% CI: 0.33–0.53) and from 48.0% (119/248) during 2004–2006 to 21.7% (689/3172) during 2016–2018 in the multiple trauma group (adjusted OR = 0.32, 95% CI: 0.23–0.45). The adjusted ORs for the 3-year increment were 0.84 (95% CI: 0.81–0.88) and 0.78 (95% CI: 0.75–0.83) for the isolated TBI and multiple trauma groups, respectively.

Conclusions
Using the national JTDB registry, we demonstrated a nationwide reduction in TBI-related mortality. Our findings in the super-aged society of Japan may provide insight for the treatment of geriatric patients with TBI worldwide.
Isolated dextrogastria with eventration of right hemidiaphragm and hiatal hernia in an adult male
Authors: Aziz Shahid , König Simone , Noor Haseeb , Nadeem Muhammad , Zahra Rabaab , Rasheed Faisal 
Published: February 2022

Abstract
Background
Type 2 isolated dextrogastria in conjunction with protrusion of the right hemidiaphragm and hiatal hernia is an uncommon anomaly among all transpositions of the viscera. Clear diagnosis is not straightforward in such cases both clinically and with various imaging techniques leaving often only laparotomy for diagnosis.

Case presentation
Here, we discuss the case of a so far asymptomatic 19-year-old male, who had a 3-month history of abdominal pain and 2 days of vomiting with absolute constipation, and reduced air entry in the base of the right lung. A large air fluid level was found in the right lower hemithorax, furthermore, a loss of the normal diaphragmatic outline, and paucity of the bowel gases in the rest of the abdomen. Computer tomography with contrast was suggestive of loss of right lung volume, with stomach and bowel loops herniating into the right hemithorax and compressive atelactatic changes in the adjacent lung alongside an enlarged liver. A barium test showed the stomach fundus and body posteriorly positioned, while both duodenal bulb loops and the duodeno-jejunal junction alongside the small and large bowels were detected in their normal positions.

Conclusion
In case of visceral transpositions, routine diagnostic blood and radiological tests may lead the health care provider to misdiagnosis. It is necessary, in particular when surgery is required, to carefully elucidate the organ anomaly. The use of additional imaging and radiological methods may be called for; CT scan and a barium test were critical here. This is the first case of isolated dextrogastria with eventration of right hemidiaphragm and hiatal hernia reported from Pakistan providing insights for diagnostic procedures.
The association between handgrip strength and depression in cancer survivors: a cross-sectional study
Authors: Zhang Xiao-Ming , Zhang Zhi-Biao , Chen Wei , Wu Xinjuan 
Published: February 2022

Abstract
Background
The association between handgrip strength and depression in cancer survivors has been unexplored until now. We aim to examine the association between handgrip strength and depression in cancer survivors by using publicly available data (National Health and Nutrition Examination Survey).

Methods
Two waves of data from the National Health and Nutrition Examination Survey, from 2011–2012 and 2013–2014, were extracted and combined to explore this important issue. We extracted maximum patient handgrip strength value (from both hands). The Patient Health Questionnaire (PHQ-9) was used to evaluate depression with a cut-off >  = 10 points indicating that patients had depressive symptoms. Other basic characteristics and health-related variables were also collected. We used Least Absolute Shrinkage and Selection Operator (LASSO) regression to select potential confounding factors. Multivariable linear or logistic regression models were adopted to explore whether handgrip strength as a continuous variable, or low handgrip strength, was associated with depressive symptoms.

Results
There were 876 cancer survivors in our present total sample, with 403 (46.0%) males and 473 females (54.0%). The mean (SD) age of the entire group was 64.67 (13.81) years. The prevalence of depression and low handgrip strength was 12.90% and 16.7%, respectively. The results showed that handgrip strength was negatively associated with depressive symptoms in cancer survivors (OR = 0.95, 95%CI:0.92–0.99; P = 0.024). In addition, after adjusting for age, gender, race; marital status, polypharmacy, sleep disorder, arthritis, congestive heart failure, history of stroke, type of cancer, chronic coronary bronchitis and being overweight, cancer survivors with low handgrip strength had a 2.02-fold risk of depression, compared to those with normal handgrip strength (OR = 2.02,95%CI:1.07–3.81; P = 0.028).

Conclusions
Our present study suggests that low handgrip strength, as a simple and modifiable parameter, is associated with a higher risk of depression in cancer survivors. Therefore, future larger-scale prospective cohort studies are warranted to determine this association.
Physical capability in a rural birth cohort at the age of 52: association with early environmental, nutritional, and developmental factors
Authors: Arroyo Pedro , Esparza-Aguilar Marcelino , Martín-Martín Verónica , Gomez-Verjan Juan Carlos , Parra-Rodríguez Lorena , Cadena-Trejo Cinthya , Salazar-Pérez Cecilia , Gutiérrez-Robledo Luis Miguel 
Published: February 2022

Abstract
Introduction
Midlife physical capability (PC) is associated with developmental factors in the populations of economically developed countries. As far as we know, there is no information for rural populations of low- and middle-income countries. The aim of the study was to investigate the influence of pre- and postnatal factors on midlife objective measures of PC in a 1966–67 birth cohort from a Mexican rural community. The hypothesis was that adverse developmental conditions are associated with low midlife PC.

Methods
In 1966–67, a birth cohort of all children from a poor Mexican rural community was assembled. Data on family socioeconomic status (SES), parental health and nutritional status, birth weight, postnatal growth and feeding patterns were registered. In 2018, out of the 336 cohort members, 118 were living in the community, and eighty-two of them underwent a comprehensive clinical evaluation. The evaluation included grip strength, gait velocity and chair-stand PC tests. In multivariable linear models, PC tests were the dependent variables, and prenatal, birth and postnatal factors were the independent variables. Adjustment for confounding was made with adult anthropometric, body composition, clinical and ageing status variables.

Results
Independent of adult health status and other ageing indicators, lower PC was associated with family organization and SES, parental nutritional status, birth weight, infant postnatal growth velocity, and weaning time. These results indicate that adverse family and environmental conditions that are prevalent in poor rural communities are associated with low midlife PC.