bluuebunny/crossref_metadata_2025_split huggingface dataset:
The lower expression of circulating miR‐210 and elevated serum levels of HIF‐1α in ischemic stroke; Possible markers for diagnosis and disease prediction
Authors: Rahmati Mina , Ferns Gordon A. , Mobarra Naser 
Published: October 2021

AbstractBackgroundStroke, either due to ischemia or hemorrhage, causes acute neurological damages to the brain. There is shortage of reliable biomarkers for ischemic stroke (IS), and we therefore investigated the serum concentrations of microRNA‐210 (miR‐210) and hypoxia inducible factor‐1α (HIF‐1α), as possible diagnostic and/or prognostic markers for IS.MethodsSerum samples were acquired from 52 IS patients and their healthy counterparts at five time points: upon admission, 24 and 48 h after admission, upon discharge and 3 months later. Serum levels of miR‐210 and HIF‐1α were respectively analyzed using real time RT‐PCR and ELISA. Diagnostic and prognostic accuracy tests were performed to assess the value of suggested biomarkers.ResultsIS patients demonstrated higher levels of serum HIF‐1α and lower miR‐210 in comparison to the healthy subjects. MiR‐210 was suggested to be a weak diagnostic biomarker at the time of admission (AUC = 0.61; p = 0.05), while HIF‐1α was an acceptable diagnostic marker for IS (AUC = 0.73; p < 0.0001). The higher expression of miR‐210 and lower levels of HIF‐1α were associated with better survivals in IS patients.ConclusionsSerum miR‐210 is a weak diagnostic marker of IS. Serum HIF‐1α is a better biomarker in diagnosing IS patients but further work in larger groups, including those with hemorrhagic stroke is necessary to confirm its diagnostic utility. Similarly, the prognostic potentiality of miR‐210 and HIF‐1α was acceptable but needs bigger sample size and longer follow‐up to be statistically confirmed.
miR‐125a‐5p promotes gastric cancer growth and invasion by regulating the Hippo pathway
Authors: Li Ruixin , Hu Zhihao , Wang Zhuoyin , Zhu Tianyu , Wang Guojun , Gao Bulang , Wang Jingtao , Deng Xiumei 
Published: October 2021

AbstractObjectiveThis study was carried out to explore the potential involvement of miR‐125a‐5p in the oncogenic effects of EphA2, TAZ, and TEAD2 and the activity of the Hippo signaling pathway in gastric cancer progression.MethodsIn vitro transfection of miR‐125a‐5p mimics or inhibitors, qRT‐PCR, colony formation assays, and cell invasion assays were used to assess the effect of miR‐125a‐5p on the growth and invasion in gastric cancer (GC). Male nude mice bearing tumors derived from human GC cells were used for evaluating the effects of miR‐125a‐5p on tumor growth. Luciferase reporter assay, immunofluorescence, immunohistochemistry, qRT‐PCR, and immunoblotting were performed to explore the role of miR‐125a‐5p in the epithelial‐mesenchymal transition (EMT) and association among miR‐125a‐5p, EphA2, TAZ, and TEAD2 in GC cells.ResultsMiR‐125a‐5p enhanced GC cell viability and invasion in vitro, whereas inhibition of miR‐125a‐5p using a specific inhibitor and antagomir suppressed cancer cell invasion and tumor growth. Moreover, inhibition of miR‐125a‐5p reversed EMT in vitro. miR‐125a‐5p upregulated the expression of EphA2, TAZ, and TEAD2, promoted TAZ nuclear translocation, and induced changes in the activity of the Hippo pathway by enhancing the expression of TAZ target genes. Finally, miR‐125a‐5p was overexpressed in late‐stage GCs, and positive correlations were observed with its targets EphA2, TAZ, and TEAD2.ConclusionmiR‐125a‐5p can promote GC growth and invasion by upregulating the expression of EphA2, TAZ, and TEAD2.
Inhibition of FABP4 attenuates hyperoxia‐induced lung injury and fibrosis via inhibiting TGF‐β signaling in neonatal rats
Authors: Huang Liang‐Ti , Chou Hsiu‐Chu , Chen Chung‐Ming 
Published: October 2021

AbstractBronchopulmonary dysplasia (BPD) is a chronic lung disease characterized by interrupted alveologenesis and alveolar simplification caused by oxygen therapy in premature infants. Metabolic dysfunction is involved in the pathogenesis of BPD. Fatty acid‐binding protein 4 (FABP4) is significantly increased in specific lung tissues in patients with BPD. Therefore, we investigated whether BMS309403, an FABP4 inhibitor that can mitigate tissue fibrosis, can regulate pulmonary fibrotic processes in newborn rats exposed to hyperoxia. Newborn rat pups were exposed to room air (RA; 21% O2) or 85% O2 from 5 to 14 days of age and were then allowed to recover in RA until 29 days of age. They received intraperitoneal injection with placebo (phosphate‐buffered saline [PBS]) or BMS 309403 (0.5 mg or 1.0 mg kg−1 d−1) every other day from 4 to 14 days of age then were divided into O2 plus PBS or low dose or high dose and RA plus PBS or low dose or high dose groups. We assessed lung histology and evaluated lung collagen I, FABP4 as well as TGF‐β1 expression at 14 and 29 days of age. In the hyperoxia injury‐recovery model, prophylactic BMS309403 treatment reduced mean linear intercept values and FABP4 expression (p < 0.001). Prophylactic BMS309403 treatment mitigated pulmonary fibrosis and TGF‐β1 expression immediately after hyperoxia exposure (p < 0.05). The attenuation of hyperoxia‐induced alveolar developmental impairment and pulmonary fibrosis by FABP4 inhibition indicated that such inhibition has potential clinical and therapeutic applications.
Population Pharmacokinetics and Exposure‐Response Modeling of Daratumumab Subcutaneous Administration in Patients With Light‐Chain Amyloidosis
Authors: Luo Man (Melody) , Zhu Peijuan (Penny) , Nnane Ivo , Xiong Yuan , Merlini Giampaolo , Comenzo Raymond L , Kastritis Efstathios , Wechalekar Ashutosh D. , Weiss Brendan M. , Tran NamPhuong , Qin Xiang , Vermeulen Jessica , Sharma Amarnath , Sun Yu‐Nien , Zhou Honghui 
Published: October 2021

AbstractThe purpose of this study is to characterize the population pharmacokinetics (popPK) of subcutaneous (SC) daratumumab in combination with bortezomib, cyclophosphamide, and dexamethasone and explore the relationship between daratumumab systemic exposure and selected efficacy and safety end points in patients with newly diagnosed systemic amyloid light‐chain amyloidosis. The popPK analysis included pharmacokinetic and immunogenicity data from patients receiving daratumumab SC in combination with bortezomib, cyclophosphamide, and dexamethasone in the ANDROMEDA study (AMY3001; safety run‐in, n = 28; randomized phase, n = 183). Nonlinear mixed‐effects modeling was used to characterize the popPK and quantify the impact of potential covariates. The exposure‐response (E‐R) analysis included data from all patients in the randomized phase of ANDROMEDA (n = 388). Logistic regression and survival analysis were used to evaluate the relationships between daratumumab systemic exposure and efficacy end points. The E‐R analysis on safety was conducted using quartile comparison and logistic regression analysis. The observed concentration‐time data of daratumumab SC were well described by a 1‐compartment popPK model with first‐order absorption and parallel linear and nonlinear Michaelis‐Menten elimination pathways. None of the investigated covariates were determined to be clinically meaningful. Daratumumab systemic exposure was generally similar across subgroups that achieved different levels of hematologic response, and there was no apparent relationship between daratumumab systemic exposure and the investigated safety end points. In conclusion, the popPK and E‐R analyses supported the selected 1800‐mg flat dose of daratumumab SC in combination with the bortezomib, cyclophosphamide, and dexamethasone regimen for the treatment of light‐chain amyloidosis. No dose adjustment was recommended for investigated covariates.
MDMA‐Assisted Psychotherapy for Treatment of Posttraumatic Stress Disorder: A Systematic Review With Meta‐Analysis
Authors: Smith Kimberly W. , Sicignano Dakota J. , Hernandez Adrian V. , White C. Michael 
Published: October 2021

AbstractThis article discusses current literature on the use of 3,4‐methylenedioxymethamphetamine (MDMA)‐assisted psychotherapy in the treatment of posttraumatic stress disorder (PTSD). MDMA, the intended active ingredient in illicit Ecstasy or Molly products, is a psychedelic that causes an elevated mood, feeling of bonding, and increased energy. In MDMA‐assisted psychotherapy, patients are subjected to 2 or 3 multihour sessions of therapy with a team of psychiatrists. The dosing of MDMA is used to allow the therapist to probe the underlying trauma without causing emotional distress. The use of MDMA‐assisted psychotherapy treatment reduced patient's Clinician‐Administered PTSD Scale (CAPS) scores from baseline more than control psychotherapy (–22.03; 95%CI, –38.53 to –5.52) but with high statistical heterogeneity. MDMA‐assisted psychotherapy enhanced the achievement of clinically significant reductions in CAPS scores (relative risk, 3.65; 95%CI, 2.39‐5.57) and CAPS score reductions sufficient to no longer meet the definition of PTSD (relative risk, 2.10; 95%CI, 1.37‐3.21) with no detected statistical heterogeneity. While therapy was generally safe and well tolerated, bruxism, anxiety, jitteriness, headache, and nausea are commonly reported. While MDMA‐assisted psychotherapy has been shown to be an effective therapy for patients with PTSD with a reasonable safety profile, use of unregulated MDMA or use in the absence of a strongly controlled psychotherapeutic environment has considerable risks.
Uncovering ART adherence inconsistencies: An assessment of sustained adherence among adolescents in South Africa
Authors: Zhou Siyanai , Cluver Lucie , Shenderovich Yulia , Toska Elona 
Published: October 2021

AbstractIntroductionAntiretroviral treatment (ART) adherence rates are lower among adolescents living with HIV (ALHIV) than among adults and children, but more evidence is needed on long‐term sustained ART adherence among ALHIV. This study assesses rates of sustained ART adherence in a cohort of adolescents in South Africa.MethodsA prospective cohort of adolescents (10‐19 years) living with HIV (baseline sample N = 1 046, 55% female, mean age 13.6) in the Eastern Cape Province in South Africa were interviewed at baseline (2014‐15) and followed‐up twice (2015‐16, 2017–18). All adolescents ever initiated on treatment in 52 government health facilities were traced (with 90% uptake, 94% retention at Wave 2, and 97% retention at Wave 3, 3.4% mortality) and their clinic records were extracted where available. We investigate sustained ART adherence among adolescents interviewed at all three waves of data collection (N = 933). To quantify adherence at each study wave, we used self‐reported past‐week adherence (including weekdays and weekends). Self‐reported adherence was validated using HIV‐1 RNA viral load (>50 copies/mL cut‐off) reported in clinic records, in a random‐intercept logistic regression.Results and discussionAt baseline, approximately 66% (N = 615) of adolescents reported past‐week ART adherence, and of these 45.3% reported adherence at both baseline and follow‐up. Only 37.1% of the sample reported sustained past‐week ART adherence over the three waves of the study. Most adolescents (N = 587, 62.9%) report inconsistent adherence across time (including 6.4% disengaged from care). Older (P = 0.007) and adolescents with horizontally acquired HIV (P = 0.002) were more likely to report inconsistent adherence across time. Controlling for socio‐demographic characteristics, past‐week adherence was associated with non‐detectable viral load (aOR 1.72, 95%CI 1.14‐2.59, P = 0.009). Overall, of the adolescents with viral load measurements at study Wave 1 and Wave 2, 50.6% maintained undetectable viral load for the preceding year.ConclusionsAdolescents living with HIV reported very low rates of sustained ART adherence. Adherence reported at a single time may mask high rates of variability in adherence over time. These findings highlight the urgent need for enhanced and effective interventions to assist ALHIV with ART adherence through the challenging years of adolescence.
Characterizing winter season severity in the Midwest United States, Part I: Climatology and recent trends
Authors: Ford Trent W. , Budikova Dagmar , Wright Jefferson D. 
Published: October 2021

AbstractSevere winter weather is a staple of Midwest United States (U.S.) climate and is an important natural hazard that has significant economic and environmental impacts. Winter season severity varies both spatially and temporally in the Midwest, and past studies have documented significant changes in Midwest winter characteristics, including increases in temperature and decreases in snow depth. In this study, we use the Accumulated Winter Season Severity Index (AWSSI) to characterize winter severity across the Midwest and assess its variability and change on various spatial and temporal scales during the 1951–2020 period. AWSSI is derived from daily records of snowfall (SF), snow depth (SD), maximum surface air temperature (TMAX), and minimum surface air temperature (TMIN) during the winter season. The daily total AWSSI index value reflects the sum of points accumulated from daily values of each of these four variables surpassing pre‐determined thresholds, and the total season sum reflects the overall winter season severity. We find AWSSI provides a unique perspective by which to describe climatological differences in winter season character in the Midwest. Namely, over three quarters of winter season days accumulate points in the northern Midwest, compared to just over half in the southern Midwest. Meanwhile, the relative contribution of extreme winter days to total winter severity is much larger in the southern Midwest than farther north. In addition, we find overall winter season severity has significantly decreased at only a quarter of stations and the frequency of extreme winter days has significantly decreased at only a fifth of stations, despite widespread increases in winter daily maximum and minimum temperature. The results suggest Midwest U.S. winter season severity as described by the AWSSI has not significantly changed over the past 70 years.
Risk of bias assessment in preclinical literature using natural language processing
Authors: Wang Qianying , Liao Jing , Lapata Mirella , Macleod Malcolm 
Published: October 2021

AbstractWe sought to apply natural language processing to the task of automatic risk of bias assessment in preclinical literature, which could speed the process of systematic review, provide information to guide research improvement activity, and support translation from preclinical to clinical research. We use 7840 full‐text publications describing animal experiments with yes/no annotations for five risk of bias items. We implement a series of models including baselines (support vector machine, logistic regression, random forest), neural models (convolutional neural network, recurrent neural network with attention, hierarchical neural network) and models using BERT with two strategies (document chunk pooling and sentence extraction). We tune hyperparameters to obtain the highest F1 scores for each risk of bias item on the validation set and compare evaluation results on the test set to our previous regular expression approach. The F1 scores of best models on test set are 82.0% for random allocation, 81.6% for blinded assessment of outcome, 82.6% for conflict of interests, 91.4% for compliance with animal welfare regulations and 46.6% for reporting animals excluded from analysis. Our models significantly outperform regular expressions for four risk of bias items. For random allocation, blinded assessment of outcome, conflict of interests and animal exclusions, neural models achieve good performance; for animal welfare regulations, BERT model with a sentence extraction strategy works better. Convolutional neural networks are the overall best models. The tool is publicly available which may contribute to the future monitoring of risk of bias reporting for research improvement activities.
Effects of almonds on ameliorating salt‐induced hypertension in dahl salt‐sensitive rats
Authors: Zeng Li , Liu Zerong , Zhou Luxin , Chen Meng , Zheng Xuewei , Yang Pengfei , Zhao Xinrui , Tian Zhongmin 
Published: October 2021

AbstractBACKGROUNDExcessive dietary salt intake is related to an increased risk of hypertension. Dietary functional foods probably could help to improve salt‐induced hypertension. In this study, Dahl salt‐sensitive (DSS) rats were used to investigate their metabolic differences from those of salt‐resistant SS.13BN rats and determine whether dietary protein‐rich almonds could ameliorate salt‐induced elevation of blood pressure in DSS rats.RESULTSAfter high‐salt intake, the systolic blood pressure and mean arterial pressure of the DSS rats increased dramatically. Metabolomics analysis indicated abnormal amino acid metabolism in their kidneys. Their renal nitric oxide (NO) content and nitric oxide synthase activity decreased significantly after high‐salt diet. Oxidative stress also occurred in DSS rats. After the DSS rats received almond supplementation, the levels of various amino acids in their kidney increased, and renal arginine and NO contents were upregulated. Their renal hydrogen peroxide and malonaldehyde levels decreased, whereas renal catalase, superoxide dismutase and glutathione peroxidase activities and glutathione levels increased.CONCLUSIONThe renal abnormal amino acid metabolism of DSS rats contributed to the impaired NO production in response to high‐salt intake. Together with salt‐induced oxidative stress, high‐salt diet intake ultimately led to an increase in the blood pressure of DSS rats. Protein‐rich almond supplementation might prevent the development of salt‐induced hypertension by restoring arginine and NO regeneration and alleviating salt‐induced oxidative stress. © 2021 Society of Chemical Industry.
High‐throughput bioanalysis of sitagliptin in plasma using direct analysis in real time mass spectrometry and its application in the pharmacokinetic study thereof
Authors: Liu Yingze , Meng Xiangjun , Zhang Yuyao , Zhang Linge , Shan Yuqin , Gu Jingkai , Sun Dong 
Published: October 2021

AbstractSitagliptin is a dipeptidyl peptidase‐IV inhibitor for the treatment of type 2 diabetes mellitus. In the present study, a sensitive and high‐throughput quantitative method based on the direct analysis in real time tandem mass spectrometry has been developed and validated for the bioanalysis of sitagliptin in rat plasma without chromatographic separation. Sitagliptin and its internal standard retagliptin were detected in positive ion mode by multiple reaction monitoring transitions at m/z 408.2→235.0 and 465.2→260.1, respectively. The method includes a simple solid‐phase extraction sample preparation procedure, through which appropriate and reproducible analytical results within the linear concentration range of 20–2000 ng/mL have been achieved. The intra‐ and interday precisions were <10.6% and the accuracies were ranging from −8.17 to 2.60%. This method has been successfully applied to the pharmacokinetic study of sitagliptin after single intravenous administration in rats. This approach shows considerable promise of direct analysis in real time tandem mass spectrometry method in the high‐throughput bioanalysis.
Otolaryngology Utilization in Patients With Achondroplasia: Results From the CLARITY Study
Authors: Tunkel David E. , Gough Ethan , Bober Michael B. , Hashmi S. Shahrukh , Hecht Jacqueline T. , Legare Janet M. , Little Mary Ellen , Modaff Peggy , Pauli Richard M. , Rodriguez‐Buritica David , Serna Maria Elena , Smid Cory J. , Hoover‐Fong Julie E. 
Published: October 2021

Objectives/HypothesisTo quantify otolaryngologic surgery utilization in patients with achondroplasia, and to identify any changes in utilization over the past four decades.Study DesignRetrospective cohort study.MethodsA retrospective cohort study of 1,374 patients with achondroplasia enrolled in the CLARITY retrospective cohort study at four centers of multi‐specialty care for patients with achondroplasia. Otolaryngologic surgeries are presented by birth cohort decade. The main outcomes were number of primary and additional otolaryngologic procedures; age at surgery; likelihood of repeated surgery; temporal trends in surgical utilization.ResultsIn this cohort of 1,374 patients with achondroplasia, 620 (45.1%) had pharyngeal surgery at least once, 150 (10.9%) had pharyngeal surgery on more than one occasion, and patients who had adenoidectomy first were 2.68 times more likely to require a second pharyngeal surgery than those who had adenotonsillectomy. Seven hundred and seventy‐nine (56.7%) had tympanostomy tubes placed at least once, and 447 (32.5%) had tympanostomy tubes placed more than one time. Age at first pharyngeal surgery decreased by 1.2 years per birth cohort decade, and age at tympanostomy tube placement decreased by 1.1 years per decade.ConclusionsPatients with achondroplasia often require otolaryngologic surgery, particularly adenoidectomy and/or tonsillectomy as well as tympanostomy tube placement. Such surgery is performed now more frequently and at younger ages than in earlier decades. While otolaryngologic disease associated with achondroplasia is now recognized earlier and treated more frequently, long‐term outcome studies are needed.Level of Evidence3 Laryngoscope, 132:1548–1554, 2022
Synthetic Triterpenoid RTA‐408: Limits Radiation Damage to Normal Tissue
Authors: Luginbuhl Adam J. , Hobelmann Kealan , Rodin Julianna , Shukla Sanket , Rodeck Ulrich , Linnenbach Alban 
Published: October 2021

Objectives/HypothesisTo assess the efficacy and mechanism of action of a novel approach to mitigate acute and chronic radiation toxicity in a validated animal model.Study DesignRandomized, prospective study using an in vivo rat model.MethodsExperimental animal study utilizing Sprague–Dawley rats divided into three cohorts: 1) radiation + dimethyl sulfoxide (DMSO) (inert vehicle); 2) radiation + RTA‐408 (therapeutic drug); and 3) no radiation + DMSO. All animals in the radiation cohorts underwent 40 Gy of radiation with subsequent inferior epigastric axial rotational flap 30 days later in all cohorts with percentage of flap necrosis and vascular density calculated by blinded observers. In a second experiment, an additional three cohorts, underwent serial punch biopsies of the abdominal skin before, during, and after radiation and drug/vehicle control treatment. Transcriptome analysis utilizing gene set enrichment analysis and digital polymerase chain reaction were performed at various time points.ResultsThe first experiment revealed average flap necrosis of 20% (95% confidence interval [CI] 16–45) in the radiation control group, 3% (95% CI 0–11) in the nonirradiated control, and 3% (95% CI 0.2–10) in the radiation group treated with RTA‐408. Vascular density was preserved in the treatment group as compared to the radiated control. Nine rats were included in the second experiment, and transcriptome analyses in the treatment group revealed robust activation of antioxidant pathways with induced expression of genes associated with hypoxia and adipogenesis/angiogenesis.ConclusionsAdministration of RTA‐408 during radiation treatment in a rat model resulted in transcriptome changes which appear to mitigate the toxic effects of radiation, preserving capillary networks and improving flap survival and tissue healing after subsequent surgery.Level of EvidenceFoundational Evidence, Animal Research Laryngoscope, 132:1196–1204, 2022