bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex Steroids and Osteoarthritis: A Mendelian Randomization Study
Authors: Yan Yi-Shang , Qu Zihao , Yu Dan-Qing , Wang Wei , Yan Shigui , Huang He-Feng 
Published: June 2021

ObjectiveSex steroids are thought to contribute to the pathogenesis of osteoarthritis (OA). This study investigated the causal role of sex steroids in site- and sex-specific OA and risk of joint replacement surgery using the Mendelian randomization (MR) method.MethodsInstrumental variables for estradiol, dehydroepiandrosterone sulfate, testosterone (T), and dihydrotestosterone (DHT) were selected. We used the inverse variance weighting (IVW) approach as the main MR method to estimate causal effects based on the summary-level data for OA and joint replacement surgery from genome-wide association studies (GWAS).ResultsA positive causal association was observed between serum T level and risks of hip OA (odds ratio [OR]=1.558, 95% confidence interval [CI]: 1.193–2.034; P=0.001) and hip replacement (OR=1.013, 95% CI: 1.008–1.018; P=2.15×10−8). Serum DHT level was also positively associated with the risk of hip replacement (OR=1.011, 95% CI: 1.006–1.015; P=4.03×10−7) and had potential causality with hip OA (OR=1.398, 95% CI: 1.054–1.855; P=0.020).ConclusionsSerum T and DHT levels may play causal roles in the development of hip OA and contribute to the risk of hip replacement, although the underlying mechanisms require further investigation.
Adenomatoid Tumor of the Adrenal Gland: Report of Two Cases and Review of the Literature
Authors: Guan Jiexia , Zhao Chang , Li Hengming , Zhang Wenjing , Lin Weizhen , Tang Luying , Chen Jianning 
Published: June 2021

Adenomatoid tumor (AT) is an uncommon benign neoplasm of mesothelial origin, usually occurring in the female and male genital tracts. Extragenital localization such as the adrenal gland is extremely rare. Until now, only 39 cases of adrenal AT have been reported in the English literature. Here we report two novel cases of adrenal AT that occurred in male patients aged 30 and 31 years. The tumors were discovered incidentally by computed tomography (CT). Macroscopically, the tumors were unilateral and solid, and the greatest dimension of the tumors was 3.5 and 8.0 cm, respectively. Histologically, the tumors consisted of angiomatoid, cystic, and solid patterns and infiltrated the adrenal cortical or medullary tissue. The tumor cells had low nuclear/cytoplasmic ratio, with no pathological mitosis or nuclear pleomorphism. Thread-like bridging strands and signet-ring-like cells could be seen. Immunohistochemically, the tumor cells were positive for epithelial markers (AE1/AE3, CK7) and mesothelial markers (D2-40, calretinin, and WT-1). The Ki-67 index was approximately 1 and 2%, respectively. The differential diagnosis of adrenal AT includes a variety of benign and malignant tumors. The patients had neither local recurrence nor distant metastasis at 21 and 8 months after removal of the tumor. In the literature review, we comprehensively summarized the clinical, morphological, immunohistochemical, and prognostic features of adrenal AT. Adrenal ATs are morphologically and immunophenotypically identical to those that occur in the genital tracts. Combining the histology with immunohistochemical profiles is very supportive in reaching the diagnosis of this benign tumor, helping to avoid misdiagnosis and overtreatment.
Multiphysics Modeling of Thorium-Based Fuel Performance With Cr-Coated SiC/SiC Composite Under Normal and Accident Conditions
Authors: Liu Shengyu , Liu Rong , Qiu Chengjie , Zhou Wenzhong 
Published: June 2021

Using the finite element multiphysics modeling method, the performance of the thorium-based fuel with Cr-coated SiC/SiC composite cladding under both normal operating and accident conditions was investigated in this work. First, the material properties of SiC/SiC composite and chromium were reviewed. Then, the implemented model was simulated, and the results were compared with those of the FRAPTRAN code to verify the correctness of the model used in this work. Finally, the fuel performance of the Th0.923U0.077O2 fuel, Th0.923Pu0.077O2 fuel, and UO2 fuel combined with the Cr-coated SiC/SiC composite cladding and Zircaloy cladding, respectively, was investigated and compared under both normal operating and accident conditions. Compared with the UO2 fuel, the Th0.923U0.077O2 and Th0.923Pu0.077O2 fuels were found to increase the fuel centerline temperature under both normal operating and reactivity-initiated accident (RIA) conditions, but decrease the fuel centerline temperature under loss-of-coolant accident (LOCA) condition. Moreover, compared to the UO2 fuel with the Zircaloy cladding, thorium-based fuels with Cr-coated SiC/SiC composite cladding were found to show better mechanical performance such as delaying the failure time by about 3 s of the Cr-coated SiC/SiC composite cladding under LOCA condition, and reducing the plenum pressure by about 0.4 MPa at the peak value in the fuel rod and the hoop strain of the cladding by about 16% under RIA condition.
Microplastics Increase Soil pH and Decrease Microbial Activities as a Function of Microplastic Shape, Polymer Type, and Exposure Time
Authors: Zhao Tingting , Lozano Yudi M. , Rillig Matthias C. 
Published: June 2021

Microplastic pollution is a topic of increasing concern, especially since this issue was first addressed in soils. Results have so far been variable in terms of effects, suggesting that there is substantial context-dependency in microplastic effects in soil. To better define conditions that may affect microplastic-related impacts, we here examined effects as a function of microplastic shape and polymer type, and we tested if effects on soil properties and soil microbial activities change with incubation time. In our laboratory study, we evaluated twelve different secondary microplastics representing four microplastic shapes: fibers, films, foams and fragments; and eight polymer types: polyamide (PA), polycarbonate (PC), polyethylene (PE), polyester (PES), polyethylene terephthalate (PET), polypropylene (PP), polystyrene (PS), and polyurethane (PU). We mixed the microplastics with a sandy soil (0.4% w/w) and incubated at 25°C for 31 days. Then, we collected soil samples on the 3rd, 11th, and 31st day, and measured soil pH, respiration and four enzyme activities (soil enzymatic activities). Our results showed that microplastics could affect soil pH, respiration and enzymatic activities depending on microplastic shape and polymer type, effects that were altered with incubation time. Soil pH increased with foams and fragments and overall decreased in the first days of incubation and then increased. Soil respiration increased with PE foams and was affected by the incubation time, declining over time. Overall, acid phosphatase activity was not affected by shape or polymer type. β-D-glucosidase activity decreased with foams, cellobiosidase activity decreased with fibers, films and foams while N-acetyl-β-glucosaminidase activities decreased with fibers and fragments. Enzymatic activities fluctuated during the incubation time, except N-acetyl-β-glucosaminidase, which showed a declining trend with incubation time. Enzymatic activities were negatively correlated with soil pH and this relationship was less strong when microplastics were added to the soil. Our study adds to the evidence that research should embrace the complexity and diversity of microplastics, highlighting the role of microplastic shape and polymer type in influencing effects; additionally, we show that incubation time is also a parameter to consider, as effects are dynamic even in the short term.
EASIX for Prediction of Outcome in Hospitalized SARS-CoV-2 Infected Patients
Authors: Luft Thomas , Wendtner Clemens-Martin , Kosely Florentina , Radujkovic Aleksandar , Benner Axel , Korell Felix , Kihm Lars , Bauer Matthias F. , Dreger Peter , Merle Uta 
Published: June 2021

BackgroundThe coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has evoked a pandemic that challenges public health-care systems worldwide. Endothelial cell dysfunction plays a key role in pathophysiology, and simple prognosticators may help to optimize allocation of limited resources. Endothelial activation and stress index (EASIX) is a validated predictor of endothelial complications and outcome after allogeneic stem cell transplantation. Aim of this study was to test if EASIX could predict life-threatening complications in patients with COVID-19.MethodsSARS-CoV-2-positive, hospitalized patients were enrolled onto a prospective non-interventional register study (n=100). Biomarkers were assessed at hospital admission. Primary endpoint was severe course of disease (mechanical ventilation and/or death, V/D). Results were validated in 126 patients treated in two independent institutions.ResultsEASIX at admission was a strong predictor of severe course of the disease (odds ratio for a two-fold change 3.4, 95%CI 1.8-6.3, p&lt;0.001), time to V/D (hazard ratio (HR) for a two-fold change 2.0, 95%CI 1.5-2.6, p&lt;0.001) as well as survival (HR for a two-fold change 1.7, 95%CI 1.2-2.5, p=0.006). The effect was retained in multivariable analysis adjusting for age, gender, and comorbidities and could be validated in the independent cohort. At hospital admission EASIX correlated with increased suppressor of tumorigenicity-2, soluble thrombomodulin, angiopoietin-2, CXCL8, CXCL9 and interleukin-18, but not interferon-alpha.ConclusionEASIX is a validated predictor of COVID19 outcome and an easy-to-access tool to segregate patients in need for intensive surveillance.
The Cerebellum Is Related to Cognitive Dysfunction in White Matter Hyperintensities
Authors: Cao Shanshan , Nie Jiajia , Zhang Jun , Chen Chen , Wang Xiaojing , Liu Yuanyuan , Mo Yuting , Du Baogen , Hu Yajuan , Tian Yanghua , Wei Qiang , Wang Kai 
Published: June 2021

ObjectiveWhite matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) is frequently presumed to be secondary to cerebral small vessel disease (CSVD) and associated with cognitive decline. The cerebellum plays a key role in cognition and has dense connections with other brain regions. Thus, the aim of this study was to investigate if cerebellar abnormalities could occur in CSVD patients with WMHs and the possible association with cognitive performances.MethodsA total of 104 right-handed patients with WMHs were divided into the mild WMHs group (n = 39), moderate WMHs group (n = 37), and severe WMHs group (n = 28) according to the Fazekas scale, and 36 healthy controls were matched for sex ratio, age, education years, and acquired resting-state functional MRI. Analysis of voxel-based morphometry of gray matter volume (GMV) and seed-to-whole-brain functional connectivity (FC) was performed from the perspective of the cerebellum, and their correlations with neuropsychological variables were explored.ResultsThe analysis revealed a lower GMV in the bilateral cerebellum lobule VI and decreased FC between the left- and right-sided cerebellar lobule VI with the left anterior cingulate gyri in CSVD patients with WMHs. Both changes in structure and function were correlated with cognitive impairment in patients with WMHs.ConclusionOur study revealed damaged GMV and FC in the cerebellum associated with cognitive impairment. This indicates that the cerebellum may play a key role in the modulation of cognitive function in CSVD patients with WMHs.
Long-Term Use of a Sensory Prosthesis Improves Function in a Patient With Peripheral Neuropathy: A Case Report
Authors: Wrisley Diane M. , McLean Gillian , Hill Jennifer Baity , Oddsson Lars I. E. 
Published: June 2021

Background: Peripheral neuropathy (PN) can result in either partial or complete loss of distal sensation resulting in an increased fall risk. Walkasins® uses a shoe insert to detect the magnitude and direction of sway and sends signals to a leg unit that provides sensory balance cues. The objective of this case report is to describe the long-term influence of the Walkasins® lower limb sensory neuroprosthesis on balance and gait for an individual with diabetic PN.Case Description: A 51-year-old male with a 3-year history of PN and a 10-year history of type II diabetes mellitus was fitted bilaterally with Walkasins® and utilized them 8–10 hours/day for more than 2 years. Although, vibration and tactile sensation thresholds were severely impaired at his 1st metatarsophalangeal joint and the lateral malleolus bilaterally he could perceive tactile stimuli from the Walkasins® above the ankles.Outcomes: Following Walkasins® use, his Activities-specific Balance Confidence Scale (ABC) scores improved from 33 to 80%. His mean Vestibular Activities of Daily Living (VADL) scores decreased from 3.54 to 1. His Functional Gait Assessment (FGA) scores increased from 13/30 to 28/30 and his miniBESTest scores improved from 15/28 to 26/28. Gait speed increased from 0.23 to 1.5 m/s. The patient described a decrease in pain and cramping throughout his lower extremities and an increase in function.Discussion: Gait and balance improved with the use of the Walkasins® and participation in a wellness program. This improvement suggests that the use of sensory substitution devices, such as the Walkasins®, may replace sensory deficits related to gait and balance dysfunction experienced by patients with PN. Further research is needed to determine if other patients will have a similar response and what the necessary threshold of sensory function is to benefit from use of the Walkasins®.
Mendelian Randomization of Dyslipidemia on Cognitive Impairment Among Older Americans
Authors: Fu Mingzhou , Bakulski Kelly M. , Higgins Cesar , Ware Erin B. 
Published: June 2021

Background: Altered lipid metabolism may be a risk factor for dementia, and blood cholesterol level has a strong genetic component. We tested the hypothesis that dyslipidemia (either low levels of high-density lipoprotein cholesterol (HDL-C) or high total cholesterol) is associated with cognitive status and domains, and assessed causality using genetic predisposition to dyslipidemia as an instrumental variable.Methods: Using data from European and African genetic ancestry participants in the Health and Retirement Study, we selected observations at the first non-missing biomarker assessment (waves 2006–2012). Cognition domains were assessed using episodic memory, mental status, and vocabulary tests. Overall cognitive status was categorized in three levels (normal, cognitive impairment non-dementia, dementia). Based on 2018 clinical guidelines, we compared low HDL-C or high total cholesterol to normal levels. Polygenic scores for dyslipidemia were used as instrumental variables in a Mendelian randomization framework. Multivariable logistic regressions and Wald-type ratio estimators were used to examine associations.Results: Among European ancestry participants (n = 8,781), at risk HDL-C levels were associated with higher odds of cognitive impairment (OR = 1.20, 95% CI: 1.03, 1.40) and worse episodic memory, specifically. Using cumulative genetic risk for HDL-C levels as a valid instrumental variable, a significant causal estimate was observed between at risk low HDL-C levels and higher odds of dementia (OR = 2.15, 95% CI: 1.16, 3.99). No significant associations were observed between total cholesterol levels and cognitive status. No significant associations were observed in the African ancestry sample (n = 2,101).Conclusion: Our study demonstrates low blood HDL-C is a potential causal risk factor for impaired cognition during aging in non-Hispanic whites of European ancestry. Dyslipidemia can be modified by changing diets, health behaviors, and therapeutic strategies, which can improve cognitive aging. Studies on low density lipoprotein cholesterol, the timing of cholesterol effects on cognition, and larger studies in non-European ancestries are needed.
Cognitive Profiles of Amyotrophic Lateral Sclerosis Differ in Resting-State Functional Connectivity: An fMRI Study
Authors: Temp Anna G. M. , Dyrba Martin , Büttner Charlotte , Kasper Elisabeth , Machts Judith , Kaufmann Jörn , Vielhaber Stefan , Teipel Stefan , Prudlo Johannes 
Published: June 2021

BackgroundHalf of all amyotrophic lateral sclerosis-frontotemporal spectrum disorder (ALS-FTSD) patients are classified as cognitively impaired, of which 10% have frontotemporal dementia (FTD), and an additional 40% suffer from a frontotemporal syndrome not severe enough to be described as dementia (cognitively impaired/ALSci). As changes in cerebral function measured by resting-state magnet resonance imaging (rs-fMRI) are known in ALS, we investigated whether group differences in resting-state functional connectivity (RSFC) networks could be observed between ALS patients with different cognitive profiles against healthy controls (HC). Furthermore, we correlated cognition and motor functioning with network connectivity.MethodsHealthy controls, 69, and 97 ALS patients underwent functional MRI scanning and cognitive assessment. The ALS patients were categorized as non-impaired (ALSni; n = 68), cognitively impaired (ALSci; n = 21), and ALS-FTD (n = 8). Group differences in connectivity of the default mode network (DMN), motor network (MN), and ventral attention network (VAN) were investigated using a full-factorial model; correlations between global cognitive performance, shifting, and motor symptom severity were established using Pearson’s correlation.ResultsAt a liberal alpha level of uncorrected p &lt; 0.005 and a cluster size exceeding 20 voxels, we found widespread decreases in functional connectivity in all three networks when comparing ALS patients to HC. Similar patterns of hypoconnectivity in the bilateral motor cortices and frontotemporal emerged when comparing the ALSci and ALS-FTD patients to those not cognitively impaired. Hyperconnectivity in the DMN temporal gyrus correlated with worse global cognition; moreover, hyperconnectivity in the VAN thalamus, insula, and putamen correlated with worse shifting ability. Better-preserved motor function correlated with higher MN connectivity. Only the motor-related effects prevailed at a more conservative significance level of pFDR&lt; 0.001.ConclusionResting-state functional connectivity differs between cognitive profiles of ALS and is directly associated with clinical presentation, specifically with motor function, and cognitive shifting.
Longitudinal Genomic Evolution of Conventional Papillary Thyroid Cancer With Brain Metastasis
Authors: Luo Han , Liao Xue , Qin Yun , Hou Qianqian , Xue Zhinan , Liu Yang , Shen Feiyang , Wang Yuelan , Jiang Yong , Song Linlin , Chen Haining , Zhang Lingyun , Wei Tao , Dai Lunzhi , Yang Li , Zhang Wei , Li Zhihui , Xu Heng , Zhu Jingqiang , Shu Yang 
Published: June 2021

BackgroundBrain metastasis is extremely rare but predicts dismal prognosis in papillary thyroid cancer (PTC). Dynamic evaluation of stepwise metastatic lesions was barely conducted to identify the longitudinal genomic evolution of brain metastasis in PTC.MethodChronologically resected specimen was analyzed by whole exome sequencing, including four metastatic lymph nodes (lyn 1–4) and brain metastasis lesion (BM). Phylogenetic tree was reconstructed to infer the metastatic pattern and the potential functional mutations.ResultsContrasting with lyn1, ipsilateral metastatic lesions (lyn2–4 and BM) with shared biallelic mutations of TSC2 indicated different genetic originations from multifocal tumors. Lyn 3/4, particularly lyn4 exhibited high genetic similarity with BM. Besides the similar mutational compositions and signatures, shared functional mutations (CDK4R24C, TP53R342*) were observed in lyn3/4 and BM. Frequencies of these mutations gradually increase along with the metastasis progression. Consistently, TP53 knockout and CDK4R24C introduction in PTC cells significantly decreased radioiodine uptake and increased metastatic ability.ConclusionGenomic mutations in CDK4 and TP53 during the tumor evolution may contribute to the lymph node and brain metastasis of PTC.
First-Line Treatment Options for PD-L1–Negative Non-Small Cell Lung Cancer: A Bayesian Network Meta-Analysis
Authors: Peng Ling , Liang Wen-Hua , Mu De-Guang , Xu Song , Hong Shao-Dong , Stebbing Justin , Liang Fei , Xia Yang 
Published: June 2021

BackgroundFirst-line treatment strategies for programmed death-ligand 1 (PD-L1) negative non-small cell lung cancer (NSCLC) patients include chemotherapy and combination with anti-angiogenesis drugs and/or immune checkpoint inhibitor. We conducted a Bayesian network meta-analysis to evaluate the efficacy of these therapeutic options.MethodsWe included phase III randomized controlled trials comparing two or more treatments in the first-line setting for NSCLC, including data in PD-L1–negative patients. First-line strategies were compared and ranked based on the effectiveness in terms of overall survival (OS) and progression-free survival (PFS). A rank was assigned to each treatment after Markov Chain Monte Carlo analyses.ResultsFourteen trials involving 14 regimens matched our eligibility criteria. For OS, none of the treatment were significantly more effective than chemotherapy. Nivolumab plus ipilimumab plus chemotherapy was probably the best option based on analysis of the treatment ranking (probability = 30.1%). For PFS, nivolumab plus chemotherapy plus bevacizumab, atezolizumab plus chemotherapy plus bevacizumab, and atezolizumab plus chemotherapy were statistically superior to chemotherapy in pairwise comparison. Nivolumab plus chemotherapy plus bevacizumab was likely to be the preferred option based on the analysis of the treatment ranking (probability = 72.9%).ConclusionsNivolumab plus chemotherapy, in combination with angiogenesis inhibition or anti-cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4), had maximal benefits for NSCLC patient of PD-L1–negative expression. These findings may facilitate individualized treatment strategies. Safety at an individual patient level should be considered in decision making. Further validation is warranted.
Systemic Administration of Tempol Attenuates the Cardiorespiratory Depressant Effects of Fentanyl
Authors: Baby Santhosh , Gruber Ryan , Discala Joseph , Puskovic Veljko , Jose Nijo , Cheng Feixiong , Jenkins Michael , Seckler James , Lewis Stephen 
Published: June 2021

Fentanyl is a high-potency opioid receptor agonist that elicits profound analgesia and suppression of breathing in humans and animals. To date, there is limited evidence as to whether changes in oxidant stress are important factors in any of the actions of acutely administered fentanyl. This study determined whether the clinically approved superoxide dismutase mimetic, Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), or a potent antioxidant, N-acetyl-L-cysteine methyl ester (L-NACme), modify the cardiorespiratory and analgesic actions of fentanyl. We examined whether the prior systemic injection of Tempol or L-NACme affects the cardiorespiratory and/or analgesic responses elicited by the subsequent injection of fentanyl in isoflurane-anesthetized and/or freely moving male Sprague-Dawley rats. Bolus injections of Tempol (25, 50 or 100 mg/kg, IV) elicited minor increases in frequency of breathing, tidal volume and minute ventilation. The ventilatory-depressant effects of fentanyl (5 μg/kg, IV) given 15 min later were dose-dependently inhibited by prior injections of Tempol. Tempol elicited dose-dependent and transient hypotension that had (except for the highest dose) resolved when fentanyl was injected. The hypotensive responses elicited by fentanyl were markedly blunted after Tempol pretreatment. The analgesic actions of fentanyl (25 μg/kg, IV) were not affected by Tempol (100 mg/kg, IV). L-NACme did not modify any of the effects of fentanyl. We conclude that prior administration of Tempol attenuates the cardiorespiratory actions of fentanyl without affecting the analgesic effects of this potent opioid. As such, Tempol may not directly affect opioid-receptors that elicit the effects of fentanyl. Whether, the effects of Tempol are solely due to alterations in oxidative stress is in doubt since the powerful antioxidant, L-NACme, did not affect fentanyl-induced suppression of breathing.