bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exercise effects on glucocorticoid-induced bone loss in adults: a systematic review and meta-analysis
Authors: Kast Stephanie , Jakob Franz , Kohl Matthias , von Stengel Simon , Kerschan-Schindl Katharina , Lange Uwe , Thomasius Friederike , Kemmler Wolfgang 
Published: February 2023

AbstractObjectivesDue to their pronounced anti-inflammatory and immunosuppressive effects, glucocorticoids (GCs) are widely used in inflammatory conditions and organ transplants. Unfortunately, GC-induced osteoporosis is one of the most common causes of secondary osteoporosis. The aim of the present systematic review and meta-analysis was to determine the effect of exercise added to GC therapy on BMD at the lumbar spine or femoral neck in people on GC therapy.MethodsA systematic literature search of five electronic databases included controlled trials with a duration of &gt;6 months and at least two study arms [glucocorticoids (GCs) and GCs and exercise (GC + EX)] were conducted up to 20 September 2022. Studies involving other pharmaceutical therapies with relevant effects on bone metabolism were excluded. We applied the inverse heterogeneity model. Outcome measures were standardized mean differences (SMDs) with 95% CIs for BMD changes at the lumbar spine (LS) and femoral neck (FN).ResultsWe identified three eligible trials with a total of 62 participants. In summary, the GC + EX intervention indicated statistically significantly higher SMDs for LS-BMD [SMD 1.50 (95% CI 0.23, 2.77)] but not for FN-BMD [0.64 (95% CI −0.89, 2.17)] compared with GC treatment alone. We observed substantial heterogeneity (LS-BMD I2 = 71%, FN-BMD I2 = 78%) between the study results.ConclusionAlthough more well-designed exercise studies are needed to address the issue of exercise effects on GC-induced osteoporosis (GIOP) in more detail, upcoming guidelines should pay more attention to the aspect of exercise for bone strengthening in GIOP.Registration numberPROSPERO: CRD42022308155
The role of iTr35 cells in the inflammatory response and fibrosis progression of systemic sclerosis
Authors: Yang Chenxi , Lu Chunxiu , Pan Jie , Zhao Cheng , Chen Zhanrui , Qin Fang , Wen Jing , Wei Wanling , Lei Ling 
Published: February 2023

Abstract

Objective
To evaluate the role of induced immunosuppressive T regulatory (iTr) 35 cells in SSc-related inflammation and fibrosis.

Methods
Sixty-eight SSc patients were enrolled in this study. Subsets of iTr35 and Tr1 were measured by flow cytometry. IL-35 and IL-10 levels were measured using ELISA. Expressions of iTr35, Tr1, fibrosis-related genes and proteins associated with signalling pathways were determined using immunofluorescence, western blot and immunohistochemistry assays.

Results
In peripheral blood, the proportions of the iTr35 cells were higher and Tr1 cells were lower than the control group. Similarly, IL-35 expression was increased, while IL-10 levels were decreased. In fibroblasts from skin tissue, the expression levels of EBI3, IL-12Ap35, Foxp3 and IL-10 were decreased, but collagen I, TGF-β, alpha smooth muscle actin (α-SMA) and fibronectin levels were increased. Phosphorylated STAT3/6 were increased, but iTr35 and Tr1 cell levels were significantly decreased. When CD4+ cells were incubated with both recombinant human (rh)IL-35 and rhIL-10, the cell numbers of iTr35 and Tr1 were greater than the same type of cells treated with rhIL-35 or rhIL-10 alone. However, the viability of conventional CD4+ T cells was decreased by gradually increasing iTr35 cells. Moreover, iTr35 cells affected α-SMA expression through the STAT3/6 signalling pathway.

Conclusion
Both iTr35 and Tr1 cells are involved in SSc-related inflammation and fibrosis. IL-35 can induce iTr35 cells, showing a synergistic effect with IL-10. We also found that iTr35 cells can inhibit T cell proliferation and differentiation via the STAT3/6 signalling pathway, thereby causing fibrosis.
Using human genetics to understand the epidemiological association between obesity, serum urate, and gout
Authors: Zhang Li , Zhang Wenqiang , Xiao Chenghan , Wu Xueyao , Cui Huijie , Yan Peijing , Yang Chao , Tang Mingshuang , Wang Yutong , Chen Lin , Liu Yunjie , Zou Yanqiu , Alfredsson Lars , Klareskog Lars , Yang Yanfang , Yao Yuqin , Li Jiayuan , Liu Zhenmi , Yang Chunxia , Jiang Xia , Zhang Ben 
Published: February 2023

Abstract

Objectives
We aimed to clarify the genetic overlaps underlying obesity-related traits, serum urate, and gout.

Methods
We conducted a comprehensive genome-wide cross-trait analysis to identify genetic correlation, pleiotropic loci, and causal relationships between obesity (the exposure variable), gout (the primary outcome) and serum urate (the secondary outcome). Summary statistics were collected from the hitherto largest genome-wide association studies conducted for BMI (N = 806 834), waist-to-hip ratio (WHR; N = 697 734), WHR adjusted for BMI (WHRadjBMI; N = 694 649), serum urate (N = 288 649), and gout (Ncases = 13 179 and Ncontrols = 750 634).

Results
Positive overall genetic correlations were observed for BMI (rg = 0.27, P = 6.62 × 10−7), WHR (rg = 0.22, P = 6.26 × 10−7) and WHRadjBMI (rg = 0.07, P = 6.08 × 10−3) with gout. Partitioning the whole genome into 1703 LD (linkage disequilibrium)-independent regions, a significant local signal at 4q22 was identified for BMI and gout. The global and local shared genetic basis was further strengthened by the multiple pleiotropic loci identified in the cross-phenotype association study, multiple shared gene–tissue pairs observed by Transcriptome-wide association studies, as well as causal relationships demonstrated by Mendelian randomization [BMI–gout: OR (odds ratio) = 1.66, 95% CI = 1.45, 1.88; WHR–gout: OR = 1.57, 95% CI = 1.37, 1.81]. Replacing the binary disease status of gout with its latent pathological measure, serum urate, a similar pattern of correlation, pleiotropy and causality was observed with even more pronounced magnitude and significance.

Conclusion
Our comprehensive genome-wide cross-trait analysis demonstrates a shared genetic basis and pleiotropic loci, as well as a causal relationship between obesity, serum urate, and gout, highlighting an intrinsic link underlying these complex traits.
Gene-x-environment analysis supports protective effects of eveningness chronotype on self-reported and actigraphy-derived sleep duration among those who always work night shifts in the UK Biobank
Authors: Akimova Evelina T , Taiji Riley , Ding Xuejie , Mills Melinda C 
Published: February 2023

Abstract
Previous research has linked having an eveningness chronotype with a higher tolerance for night shift work, suggesting the ability to work nights without health consequences may partially depend upon having a circadian clock optimized for these times. As chronotypes entrain over time to environmental cues, it remains unclear whether higher relative eveningness among healthy night workers reflects a moderating or mediating effect of chronotype on health. We address these concerns conducting a genome-wide association study and utilizing a polygenic score (PGS) for eveningness as a time-invariant measure of chronotype. On a sample of 53 211 workers in the UK Biobank (2006–2018), we focus on the effects of night shift work on sleep duration, a channel through which night shift work adversely affects health. We ask whether a higher predisposition toward eveningness promotes night shift work tolerance. Results indicate that regular night shift work is associated with a 13-minute (3.5%) reduction in self-reported sleep per night relative to those who never work these hours (95% confidence interval [CI] = −17:01, −8:36). We find that eveningness has a strong protective effect on night workers: a one-SD increase in the PGS is associated with a 4-minute (28%) reduction in the night shift work sleep penalty per night (CI = 0:10, 7:04). This protective effect is pronounced for those working the longest hours. Consistent patterns are observed with an actigraphy-derived measure of sleep duration. These findings indicate that solutions to health consequences of night shift work should take individual differences in chronotype into account.
Delineating Marker-Trait Associations for Fusarium Wilt in Chickpea Using the Axiom®CicerSNP Array
Authors: Rasool Bushra , Summuna Baby , Djalovic Ivica , Shah Tariq Ahmad , Sheikh Parveez Ahmed , Gupta Sachin , Tyagi Sandhya , Bilal Sierra , Varshney Rajeev Kumar , Abidi Ishfaq , Kumar Jitendra , Penmetsa R. Varma , Khandey Imtiyaz , Kumar Upendra , Sofi Parvaze Ahmad , Khan Mohd Anwar , Bhat Mohd Ashraf , Wani Fahim Jeelani , Thudi Mahendar , Mir Reyazul Rouf 
Published: February 2023

Fusarium wilt (FW) caused by Fusarium oxysporum f. sp. ciceri is a devastating disease of chickpea ( Cicer arietinum). To identify promising resistant genotypes and genomic loci for FW resistance, a core set of 179 genotypes of chickpea was tested for FW reactions at the seedling and reproductive stages under field conditions and controlled conditions in the greenhouse. Our results revealed that at the seedling stage, most of the genotypes were resistant, whereas at the reproductive stage, most of the genotypes were susceptible. Genotyping using a 50K Axiom®CicerSNP Array and trait data of FW together led to the identification of 26 significant ( P ≤ E-05) marker-trait associations (MTAs) for FW resistance. Among the 26 MTAs, 12 were identified using trait data recorded in the field (three at the seedling and nine at the reproductive stage), and 14 were identified using trait data recorded under controlled conditions in the greenhouse (six at the seedling and eight at the reproductive stage). The phenotypic variation explained by these MTAs varied from 11.75 to 15.86%, with an average of 13.77%. Five MTAs were classified as major, explaining more than 15% of the phenotypic variation for FW, and two were declared stable, being identified in two environments. One of the promising stable and major MTAs (Affx_123280060) detected in field conditions at the reproductive stage was also detected in greenhouse conditions at the seedling and reproductive stages. The stable and major (>15% PVE) MTAs can be used in chickpea breeding programs.
A whole blood approach improves speed and accuracy when measuring mitochondrial respiration in intact avian blood cells
Authors: Nord Andreas , Chamkha Imen , Elmér Eskil 
Published: February 2023

AbstractUnderstanding mitochondrial biology and pathology is key to understanding the evolution of animal form and function. However, mitochondrial measurement often involves invasive, or even terminal, sampling, which can be difficult to reconcile in wild models or longitudinal studies. Non‐mammal vertebrates contain mitochondria in their red blood cells, which can be exploited for minimally invasive mitochondrial measurement. Several recent bird studies have measured mitochondrial function using isolated blood cells. Isolation adds time in the laboratory and might be associated with physiological complications. We developed and validated a protocol to measure mitochondrial respiration in bird whole blood. Endogenous respiration was comparable between isolated blood cells and whole blood. However, respiration towards oxidative phosphorylation was higher in whole blood, and whole blood mitochondria were better coupled and had higher maximum working capacity. Whole blood measurement was also more reproducible than measurement on isolated cells for all traits considered. Measurements were feasible over a 10‐fold range of sample volumes, although both small and large volumes were associated with changes to respiratory traits. The protocol was compatible with long‐term storage: after 24 h at 5°C without agitation, all respiration traits but maximum working capacity remained unchanged, the latter decreasing by 14%. Our study suggests that whole blood measurement provides faster, more reproducible, and more biologically and physiologically relevant (mitochondrial integrity) assessment of mitochondrial respiration. We recommend future studies to take a whole blood approach unless specific circumstances require the use of isolated blood cells.
Opioid Use Disorder Among the Economically Disadvantaged in the Rural South
Authors: Albright David L. , Suntai Zainab , McDaniel Justin T. , Johnson Karen , Henson Harvey , Robertson Ellen , McIntosh Shanna 
Published: February 2023

Objective
This study aimed to identify county-level hotspots and associated risk factors for opioid use disorder (OUD) in the state of Alabama.

Methods
Using 2015 to 2019 Alabama Medicaid administrative claims data, Medicaid recipients with OUD were identified. We performed local indicators of spatial association analysis to identify hotspots of OUD rates. Using logistic regression, we examined county-level social determinants of health associated with county OUD hotspots.

Results
There was a +14.13% percentage change from 2015 to 2019. The county level local indicators of spatial association analysis found that 5 counties in the northwestern part of Alabama remained “hotspots” throughout the entire study period. Results of the logistic regression model showed that location within the Appalachian region was an independent predictor of high OUD rates (b = 2.58; adjusted odds ratio, 13.27, P = 0.04).

Conclusions
The high rates of OUD may reflect the economic distress and lack of access to resources germane to the Appalachian region in Alabama.
Pregnancy Outcomes in Patients After Completion of the mRNA Coronavirus Disease 2019 (COVID-19) Vaccination Series Compared With Unvaccinated Patients
Authors: Morgan John A. , Biggio Joseph R. , Martin Jane K. , Mussarat Naiha , Elmayan Ardem , Chawla Harsheen K. , Kandalaft Savannah , Magalski Gabrielle R. , Puri Priya , Williams Frank B. 
Published: February 2023

OBJECTIVE:
To compare frequency of perinatal death between pregnant patients who completed the mRNA coronavirus disease 2019 (COVID-19) vaccination series and unvaccinated patients.

METHODS:
This retrospective cohort study included 15,865 pregnant patients who delivered 16,132 newborns after 20 weeks of gestation within a large regional health system between January 1, 2021, and December 31, 2021. Patients who received two doses of mRNA vaccine (Pfizer–BioNTech [BNT162b2] or Moderna [mRNA-1273]) were included in the vaccinated group and were compared with unvaccinated patients. Exclusions included partial vaccination, viral-vector vaccine, major congenital anomalies, and higher-order multiple gestation. Our primary outcome was perinatal death, including stillbirth and neonatal death, which was evaluated by logistic regression. Unadjusted odds ratios and adjusted odds ratios (aORs) were reported, controlling for age, body mass index (BMI), diabetes, hypertension, smoking, twin gestation, and insurance status. Propensity score matching was also performed.

RESULTS:
A total of 15,865 patients were included in the final analysis: 2,069 in the vaccination group and 13,796 in the control group. Only 13.0% of the cohort was included in the vaccination group; however, the vaccination rate increased over the course of the study period as the vaccine became more widely available and accepted. Vaccinated patients were older, with higher rates of people of non-Black racial non-Hispanic ethnic backgrounds, people with private insurance, and those with higher BMIs. Vaccination was associated with a lower incidence of perinatal death (0.5% vaccinated group vs 0.8% unvaccinated group, aOR 0.20 0.05–0.88). Vaccination against COVID-19 was also associated with lower rates of preterm delivery (aOR 0.63, 0.48–0.82), neonates with very low birth weight (aOR 0.35, 0.15–0.84), and neonatal intensive care unit (NICU) admission (aOR 0.66, 0.52–0.85). The association between vaccination and lower rates of perinatal death was no longer significant after propensity score matching.

CONCLUSION:
In a large retrospective cohort study, receipt of the primary mRNA COVID-19 vaccination series was associated with a lower rate of several adverse pregnancy outcomes, including perinatal death, preterm delivery, neonates with very low birth weight, and NICU admission. Although the decreased rates of perinatal death did not remain significant after propensity score matching, there was evidence of directional benefit for vaccinated patients.
Ultrasonography of the Explanted Uterus in Placenta Accreta Spectrum
Authors: Einerson Brett D. , Kennedy Anne , Silver Robert M. , Branch D. Ware , Comstock Jessica , Woodward Paula J. 
Published: February 2023

OBJECTIVE:
To better understand placenta accreta spectrum (PAS) by correlating postoperative ultrasonographic findings of the explanted uteroplacental interface with intraoperative findings and gross pathology.

METHODS:
We enrolled consecutive pregnant patients aged 18 years and older with a prior cesarean delivery and antenatal diagnosis of lower uterine segment PAS who planned to undergo hysterectomy into this prospective, descriptive study. All underwent cesarean hysterectomy with standardized intraoperative photography. Ultrasonography of explanted postsurgical uteruses was performed by expert radiologists to obtain standard detailed images of the myometrial–placental interface and other areas of interest. Sagittal views of the gross pathologic specimen were photographed. We correlated the intraoperative, ultrasonographic, and gross pathologic findings as a study team and report four consistent patterns that emerged from this systematic evaluation.

RESULTS:
Thirty-four consecutive eligible patients were enrolled. The following consistent observations emerged: 1) The uteroplacental interface in the explanted specimen was smooth and distinct. At the point of maximal placental protrusion, the myometrium was imperceptible, but the placenta was confined by a smooth thin echogenic line of uterine serosa (the scar shell) unless surgically disrupted. 2) Every specimen of PAS grade 2–3 showed placenta bulging through the lower uterine segment in the region of prior hysterotomy. 3) Placentas extended to, but not through, the uterovesical interface or scar shell. Dense adhesive disease was found between the placenta and bladder. There were no cases of true bladder invasion. 4) Placental extension beyond the serosa (invasion) has a distinct appearance on postoperative ultrasonography with irregular frond-like protrusion of placental tissue. This appearance was always the result of surgical manipulation and was not present before delivery of the neonate.

CONCLUSION:
These findings suggest that PAS severity is likely mediated by progressive scar dehiscence and uterine remodeling, not placental invasion. This challenges the existence of in situ invasive percreta as it is currently described.
The Quality of Preoperative Glycemic Control Predicts Insulin Sensitivity During Major Upper Abdominal Surgery: A Case-Control Study
Authors: Omiya Keisuke , Sato Hiroaki , Sato Tamaki , Nooh Abdulwahaab , Koo Bon-Wook , Kandelman Stanislas , Schricker Thomas 
Published: February 2023

Objective:
To examine the association of the quality of preoperative glycemic control and insulin sensitivity during major upper abdominal surgery.

Background:
In cardiac surgery, glycated hemoglobin A1c (HbA1c), an indicator of glycemic control during the preceding 3 months, correlated with intraoperative insulin sensitivity. Furthermore, insulin resistance showed a significant association with adverse clinical outcomes.

Methods:
This study is a post hoc exploratory analysis of a randomized controlled trial in patients undergoing elective hepatectomy and receiving the hyperinsulinemic-normoglycemic clamp (HNC) as a potential intervention to reduce surgical site infections (ClinicalTrials.gov NCT01528189). Immediately before skin incision, the HNC was initiated by infusing insulin at the rate of 2 mU/kg/min. Dextrose was administered at rates titrated to maintain normoglycemia (4.0–6.0 mmol/L). The average of 3 consecutive dextrose infusion rates during steady state was used as a measure of insulin sensitivity. Primary outcome was the relationship between preoperative HbA1c and insulin sensitivity during surgery. Secondary outcomes were the associations of insulin sensitivity with the patient’s body mass index (BMI) and postoperative morbidity.

Results:
Thirty-four patients were studied. HbA1c (Y = −0.52X + 4.8, P < 0.001, R
2 = 0.29), BMI (Y = −0.12X + 5.0, P < 0.001, R
2 = 0.43) showed negative correlations with insulin sensitivity. The odds ratio of postoperative complications within 30 days of surgery for every increase in insulin sensitivity by 1 mg/kg/min was 0.22 (95% confidential interval, 0.06–0.59; P = 0.009).

Conclusions:
We demonstrate significant associations of the quality of preoperative glycemic control and body mass index with insulin sensitivity during hepatectomy. The degree of insulin resistance correlated with postoperative morbidity.
Novel Coagulation Test Detects Anticoagulation Resistance and Is Associated With Thrombotic Events in Pediatric Patients Requiring Extracorporeal Membrane Oxygenation
Authors: Frydman Galit H. , Berger Barry M. , Kostousov Vadim , Bruzdovski Karen , Papageorgiou Dimitrios P. , Navaei Amir , Hui Shiu-Ki Rocky , Teruya Jun 
Published: February 2023

OBJECTIVES:
Bivalirudin, an IV direct thrombin inhibitor, and unfractionated heparin (UFH) are frequently used anticoagulants in the pediatric critical care setting. An accurate, specific, point-of-care test to quantify and detect anticoagulation resistance is not currently available. This study evaluates the ability of a rapid (< 10 min), micro-volume (< 50 uL) coagulation test to detect and quantify the anticoagulation effect of bivalirudin and UFH using a functional, clot time endpoint in pediatric critical care patients.

DESIGN:
Single-site retrospective laboratory sample analysis and chart review.

SETTING:
A 105-bed pediatric and cardiac ICUs delivering extracorporeal membrane oxygenation.

SUBJECTS:
Forty-one citrated, frozen, biobanked plasma specimens comprising 21 with bivalirudin and 20 with UFH from 15 anticoagulated pediatric patients were analyzed. Thirteen patients were on extracorporeal membrane oxygenation, one had a submassive pulmonary embolism, and one was on a left ventricular assist device.

INTERVENTIONS:
None.

MEASUREMENT AND MAIN RESULTS:
A Clotting Time Score (CTS) was derived on each sample. The CTS detected patients that had developed a pathologic clotting event with 100% sensitivity and 82% specificity compared with prothrombin time with 25% sensitivity/76% specificity and activated partial thromboplastin time with 0% sensitivity/0% specificity. Additionally, the CTS detected subtherapeutic anticoagulation in response to UFH in patients that were clinically determined to be UFH resistant requiring alternative anticoagulation with bivalirudin.

CONCLUSIONS:
The CTS appears to be a clinically valuable indicator of coagulation status in patients treated with either UFH or bivalirudin. Results outside of the therapeutic range due to inadequate dosing or anticoagulation resistance appeared to be associated with clot formation. CTS testing may reduce the risk of anticoagulation-related complications via the rapid identification of patients at high risk for pathologic thrombotic events.