bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physics‐informed neural network applied to surface‐tension‐driven liquid film flows
Authors: Nakamura Yo , Shiratori Suguru , Takagi Ryota , Sutoh Michihiro , Sugihara Iori , Nagano Hideaki , Shimano Kenjiro 
Published: April 2022

AbstractA physics‐informed neural network (PINN), which has been recently proposed by Raissi et al. [J Comput Phys. 2019;378:686–707], is applied to the partial differential equation (PDE) of liquid film flows. The PDE considered is the time evolution of the thickness distribution owing to the Laplace pressure, which involves fourth‐order spatial derivative and fourth‐order nonlinear term. Even for such a PDE, it is confirmed that the PINN can predict the solutions with sufficient accuracy. Nevertheless, some improvements are needed in training convergence and accuracy of the solutions. The precision of floating‐point numbers is a critical issue for the present PDE. When the calculation is executed with a single precision floating‐point number, the optimization is terminated due to the loss of significant digits. Calculation of the automatic differentiation dominates the computational time required for training and becomes exponentially longer with increasing order of derivatives. By splitting the original fourth‐order single PDE into lower‐order coupled PDEs, the computational time for each training iteration is greatly reduced. The sampling density of training data also significantly affects training convergence. For the problem considered in this study, improved convergence was obtained by allowing the sampling density of training data to be greater in earlier time ranges, where the rapid flattening of the thickness occurs.
Petrogenesis and geodynamic significance of Late Triassic mafic microgranular enclaves and its host granodiorite in the Shuanghu area, central Qiangtang
Authors: Xie Linze , Lu Rukui , Huang Yuanyi , Liu Kui , Nan Guowei 
Published: April 2022

The genesis of Late Triassic granitoids in the central Qiangtang is significant for deducing the evolution of the Palaeo‐Tethys Ocean in Qiangtang Block. Herein, we present a comprehensive study of zircon U–Pb ages, whole‐rock geochemistry and zircon Lu–Hf isotopes for the mafic microgranular enclaves (MMEs) and host granodiorites from the Shuanghu area, in order to evaluate their petrogenesis and geodynamic implications. New zircon U–Pb dating show identical formation ages for host granodiorites (207.1 ± 2.2 Ma and 206.6 ± 3.8 Ma) and MMEs (205.4 ± 2.9 Ma and 209.2 ± 2.2 Ma). The Shuanghu granodiorites contain amphibole and biotite and are characterized by moderate SiO2 (64.74–66.40 wt%) and K2O contents (2.48–3.62 wt%) as well as low A/CNK (0.69–1.00), indicating I‐type granite affinity. Its enriched zircon Hf isotopes (εHf(t) = −12.04 to −5.09) indicate that they were derived from the ancient mafic lower crust. The MMEs have a similar mineral assemblage, emplacement ages, trace elemental and zircon Hf isotopic compositions with the host granodiorites, indicating the cognate origin. These MMEs represent autoliths captured by latter ascending host magmas in the middle‐upper magma chamber. The highly variable Mg# (37–53), Cr (16.9–190 ppm) and Ni (5.71–67.2 ppm) in the Shuanghu MMEs and host granodiorites indicate that the mantle‐derived magma provided not only the heat but also the mafic components. In combining with previous studies, we suggest that the Shuanghu granodiorites and MMEs were formed in the post‐collision stage, which were caused by the asthenosphere upwelling related to the slab breakoff.
Genetic variants in CYP2B6 and HSD17B12 associated with risk of squamous cell carcinoma of the head and neck
Authors: Liu Hongliang , Li Guojun , Sturgis Erich M. , Shete Sanjay , Dahlstrom Kristina R. , Du Mulong , Amos Christopher I. , Christiani David C. , Lazarus Philip , Wei Qingyi 
Published: April 2022

AbstractPolycyclic aromatic hydrocarbons (PAH) and tobacco‐specific nitrosamines (TSNA) metabolism‐related genes play an important role in the development of cancers. We assessed the associations of genetic variants in genes involved in the metabolism of PAHs and TSNA with risk of squamous cell carcinoma of the head and neck (SCCHN) in European populations using two published genome‐wide association study datasets. In the single‐locus analysis, we identified two SNPs (rs145533669 and rs35246205) in CYP2B6 to be associated with risk of SCCHN (P = 1.57 × 10−4 and .004, respectively), two SNPs (EPHX1 rs117522494 and CYP2B6 rs145533669) to be associated with risk of oropharyngeal cancer (P = .001 and .004, respectively), and one SNP (rs4359199 in HSD17B12) to be associated with risk of oral cancer (P = .006). A significant interaction effect was found between rs4359199 and drinking status on risks of SCCHN and oropharyngeal cancer (P < .05). eQTL and sQTL analyzes revealed that two SNPs (CYP2B6 rs35246205 and HSD17B12 rs4359199) were correlated with alternative splicing or mRNA expression levels of the corresponding genes in liver cells (P < .05 for both). In silico functional annotation suggested that these two SNPs may regulate mRNA expression by affecting the binding of transcription factors. Results from phenome‐wide association studies presented significant associations between these genes and risks of other cancers, smoking behavior and alcohol dependence (P < .05). Thus, our study provided some insight into the underlying genetic mechanism of head and neck cancer, which warrants future functional validation.
Mendelian randomization analyses of 23 known and suspected risk factors and biomarkers for breast cancer overall and by molecular subtypes
Authors: Chen Fa , Wen Wanqing , Long Jirong , Shu Xiang , Yang Yaohua , Shu Xiao‐Ou , Zheng Wei 
Published: April 2022

AbstractMany risk factors have been identified for breast cancer. The potential causality for some of them remains uncertain, and few studies have comprehensively investigated these associations by molecular subtypes. We performed a two‐sample Mendelian randomization (MR) study to evaluate potential causal associations of 23 known and suspected risk factors and biomarkers with breast cancer risk overall and by molecular subtypes using data from the Breast Cancer Association Consortium. The inverse‐variance weighted method was used to estimate odds ratios (OR) and 95% confidence interval (CI) for association of each trait with breast cancer risk. Significant associations with breast cancer risk were found for 15 traits, including age at menarche, age at menopause, body mass index, waist‐to‐hip ratio, height, physical activity, cigarette smoking, sleep duration, and morning‐preference chronotype, and six blood biomarkers (estrogens, insulin‐like growth factor‐1, sex hormone‐binding globulin [SHBG], telomere length, HDL‐cholesterol and fasting insulin). Noticeably, an increased circulating SHBG was associated with a reduced risk of estrogen receptor (ER)‐positive cancer (OR = 0.83, 95% CI: 0.73‐0.94), but an elevated risk of ER‐negative (OR = 1.12, 95% CI: 0.93‐1.36) and triple negative cancer (OR = 1.19, 95% CI: 0.92‐1.54) (Pheterogeneity = 0.01). Fasting insulin was most strongly associated with an increased risk of HER2‐negative cancer (OR = 1.94, 95% CI: 1.18‐3.20), but a reduced risk of HER2‐enriched cancer (OR = 0.46, 95% CI: 0.26‐0.81) (Pheterogeneity = 0.006). Results from sensitivity analyses using MR‐Egger and MR‐PRESSO were generally consistent. Our study provides strong evidence supporting potential causal associations of several risk factors for breast cancer and suggests potential heterogeneous associations of SHBG and fasting insulin levels with subtypes of breast cancer.
Trimetazidine, a metabolic modulator, attenuates silica‐induced pulmonary fibrosis and decreases lactate levels and LDH activity in rats
Authors: Abdelrahman Rehab S. , Shawky Noha M. 
Published: April 2022

AbstractPulmonary fibrosis has been recently linked to metabolic dysregulation. Silica‐induced pulmonary fibrosis in rats was employed by the current study to explore the effects of trimetazidine (a metabolic modulator‐antianginal drug; TMZ) on silica‐induced pulmonary fibrosis. Pulmonary fibrosis was induced by intranasal instillation of silica (50 mg/100 µl/rat) in TMZ versus vehicle‐treated rats. Body weights of rats, weights of lungs, and wet‐to‐dry lung weights were determined. Various parameters were also measured in serum, bronchoalveolar lavage fluid (BALF) in addition to lung tissue homogenates. Moreover, histopathological examination of sectioned lungs for lesion score and distribution and histochemical detection of myeloperoxidase (MPO) in lung tissues were also performed. No significant differences were observed in body weight gains, lung coefficients, lung weights, and wet‐to‐dry lung weight in silica versus control rats. Elevated lactate levels in serum and lung homogenates were significantly attenuated by TMZ. In addition, lactate dehydrogenase activity, transforming growth factor‐β, and total proteins in BALF were significantly normalized with TMZ. Moreover, TMZ significantly increased reduced glutathione and adenosine triphosphate levels and decreased nitrate/nitrite and hydroxyproline content in lungs of silica‐treated rats. Histopathological examination of lungs revealed more than 56% reduction in lesion score and distribution by TMZ. MPO expression in lungs of silica‐treated rats was also significantly attenuated by TMZ. TMZ attenuates silica‐induced pulmonary fibrosis, an effect that could be mediated by suppressing anaerobic glycolysis‐induced excessive lactate production. Regulation of oxidative stress could also play a role in TMZ‐promoted protective effects.
The value of neutrophil‐to‐lymphocyte ratio combined with the thyroid imaging reporting and data system in the diagnosis of the nature of thyroid nodules
Authors: Zhang Jie , Gong Zhaoxia , Li Shanshan , Fan Ping , Yue Guanru , Zou Guilin , He Shasha , Wang Jiao , Xu Jixiong 
Published: April 2022

AbstractObjectiveThe aim of this study was to investigate the diagnostic value of peripheral blood neutrophil‐to‐lymphocyte ratio (NLR) combined with the thyroid imaging reporting and data system (TIRADS) for benign and malignant thyroid nodules.MethodsA total of 585 adults were enrolled in the study. The receiver operating characteristic curves were used to determine the optimal cut‐off values for NLR and Kwak TIRADS (K‐TIRADS) grades, which were 1.87 and 4a, respectively. Thyroid nodules were scored as follows: NLR–K‐TIRADS score is 2 (both elevated K‐TIRADS grade and NLR), NLR–K‐TIRADS score is 1 (one of these was elevated) and NLR–k‐TIRADS score is 0 (neither were elevated).ResultsThe proportions of malignant nodules with NLR‐K‐TIRADS scores of 2, 1 and 0 were 98.59%, 69.62% and 10.19%, and the difference was statistically significant (p < 0.001). In terms of the sensitivity of diagnosis of malignant nodules, NLR‐K‐TIRADS 1 tends to increase relative to K‐TIRADS grades ≥ 4a; in terms of specificity and positive predictive value for the diagnosis of malignant nodules, NLR–K‐TIRADS 2 was significantly higher than K‐TIRADS grades ≥ 4a (all p < 0.05).ConclusionsNLR combined with K‐TIRADS grades may be a novel method for screening benign and malignant thyroid nodules.
Effect of vitamin D on oxidative stress and serum inflammatory factors in the patients with type 2 diabetes
Authors: Gu Jie‐Chao , Wu Yue‐Guan , Huang Wei‐Gang , Fan Xiu‐Jing , Chen Xin‐Hao , Zhou Biao , Lin Zhi‐Jun , Feng Xiu‐Lan 
Published: April 2022

AbstractThe type 2 diabetes mellitus (T2DM) is an urgent global health problem. T2DM patients are in a state of high oxidative stress and inflammation. Vitamin D and glutathione (GSH) play crucial roles in antioxidation and anti‐inflammation. However, T2DM patients have lower vitamin D and GSH levels than healthy persons. A randomized controlled trial was conducted to see the effect of the vitamin D supplementation on oxidative stress and inflammatory factors in T2DM patients. In this study, a total of 178 T2DM patients were randomly enrolled, 92 patients received regular treatment (T2DM group) and 86 patients in Vitamin D group received extra vitamin D 400 IU per day in addition to regular treatment. Serum vitamin D, GSH, GSH metabolic enzyme GCLC and GR, inflammatory factor MCP‐1, and IL‐8 levels were investigated. We found that the T2DM group has significantly higher concentrations of MCP‐1 and IL‐8 than those in the healthy donor group. After vitamin D supplementation for 90 days, T2DM patients had a 2‐fold increase of GSH levels, from 2.72 ± 0.84 to 5.76 ± 3.19 μmol/ml, the concentration of MCP‐1 decreased from 51.11 ± 20.86 to 25.42 ± 13.06 pg/ml, and IL‐8 also decreased from 38.21 ± 21.76 to 16.05 ± 8.99 pg/ml. In conclusion, our study demonstrated that vitamin D could regulate the production of GSH, thereby reducing the serum levels of MCP‐1 and IL‐8, alleviating oxidative stress and inflammation, providing evidence of the necessity and feasibility of adjuvant vitamin D treatment among patients with T2DM. On the other hand, vitamin D and GSH levels have important diagnostic and prognostic values in T2DM patients.
Remote cognitive‐behavioral therapy for generalized anxiety disorder: A preliminary meta‐analysis
Authors: Trenoska Basile Vesna , Newton‐John Toby , Wootton Bethany M. 
Published: April 2022

AbstractBackgroundGeneralized anxiety disorder (GAD) is a chronic mental health condition that results in significant individual, societal, and economic burden. While cognitive behavioral therapy (CBT) is well established as an efficacious treatment for GAD, individuals have identified several logistical barriers to accessing face‐to‐face CBT. Remotely delivered treatments address many of these treatment barriers.MethodsThe aim of the current study was to synthesize the current literature on the efficacy of remote CBT for GAD using a meta‐analytic approach. Relevant articles were identified through an electronic database search and 10 studies (with 11 remote conditions and 1071 participants) were included in the meta‐analysis.ResultsWithin‐group findings indicate that remote CBT for GAD results in large effect sizes from pretreatment to posttreatment (g = 1.30; 95% confidence interval [CI]: 1.03−1.58). Both low intensity and high intensity remote CBT interventions were found to result in large effect sizes (g = 1.36; 95% CI: 1.11−1.61 andg = 0.83; 95% CI: 0.20−1.47, respectively), with no significant differences between the treatment formats (Q1 = 2.28,p = 0.13). Between‐group effect sizes were medium in size at posttreatment (g = 0.76; 95% CI: 0.47−1.06).ConclusionsThese findings have potential implications for the delivery of evidence‐based treatment for GAD and the inclusion of remote methods in stepped care treatment approaches.
Dapagliflozin Pharmacokinetics Is Similar in Adults With Type 1 and Type 2 Diabetes Mellitus
Authors: Melin Johanna , Tang Weifeng , Rekić Dinko , Hamrén Bengt , Penland Robert C. , Boulton David W. , Parkinson Joanna 
Published: April 2022

AbstractDapagliflozin improves glycemic control in patients with type 2 diabetes mellitus (T2DM) and is approved in Japanese patients with type 1 diabetes mellitus (T1DM) with inadequate glycemic control. The objectives of this work were to characterize the dapagliflozin pharmacokinetics (PK) in patients with T1DM, assess the influence of covariates on dapagliflozin PK, and compare dapagliflozin systemic exposure between patients with T1DM and T2DM. Population PK analysis was performed using a nonlinear mixed‐effect modeling approach. The analysis included 5793 dapagliflozin plasma concentrations from 1150 adult patients with T1DM (global population), who were on routine insulin therapy, collected from 1 phase 2 (NCT01498185) and 2 phase 3 (DEPICT‐1, NCT02268214; DEPICT‐2, NCT02460978) studies. Covariate effects were investigated using stepwise covariate modeling. Model‐derived area under the concentration‐time curve (AUC) in patients with T1DM was compared to AUC in patients with T2DM (using data from historical dapagliflozin studies). The final 2‐compartmental model adequately described the dapagliflozin concentrations in patients with T1DM. The estimated apparent clearance was 20.5 L/h. Renal function (measured as estimated glomerular filtration rate), sex, and body weight were identified as covariates, where patients with better renal function, male patients, and heavier patients had lower dapagliflozin systemic exposure. Among the covariates studied, none of the covariates affected dapagliflozin systemic exposure >1.4‐fold compared to a reference individual and were therefore deemed to be not clinically relevant. Dapagliflozin systemic exposure was comparable between patients with T1DM and T2DM.
Associations between physical frailty and living arrangements in Japanese older adults living in a rural remote island: The Shimane CoHRE study
Authors: Miyazaki Ryo , Abe Takafumi , Yano Shozo , Okuyama Kenta , Sakane Naoki , Ando Hitoshi , Isomura Minoru , Yamasaki Masayuki , Nabika Toru 
Published: April 2022

AbstractBackgroundLiving arrangements have been known to be associated with physical frailty. However, the prevalence of frailty and its risk factors in remote islands is not understood. We examined the association between living arrangements and objectively measured frailty among older adults living in a remote island of Japan.MethodsAmong older people living in Okinoshima, 656 older adults (75.6 ± 6.4 years) were analyzed. Physical frailty (robust, prefrailty, or frailty) was assessed using the 5‐item frailty phenotype (unintentional weight loss, self‐reported exhaustion, weakness, slow walking speed, and low physical activity). Physical functions (muscle mass, gait speed, and grip strength) were measured objectively.ResultsThe prevalence of frailty and prefrailty was 6.6% and 43.8%, respectively. Living with a spouse resulted in a significantly lower prevalence of frailty (p < 0.001) compared with other living arrangements. All objectively measured physical functions among those who lived with a spouse were significantly superior to those who lived with family or alone (p < 0.001). Multinomial logistic regression showed that living alone was significantly associated with frailty (odds ratio [OR] 2.36, 95% confidence interval [CI] 1.07–5.24) and prefrailty (OR 1.75, 95% CI 1.14–2.69) after adjusting for all covariates.ConclusionThe prevalence of frailty on remote islands seemed similar to that in urban areas. Older people living in remote islands might be able to maintain their physical health. Furthermore, living alone may correlate with increased risks of frailty and prefrailty. Among elderly individuals on remote islands, living with a spouse might be desirable to prevent (pre)frailty.
Thermo‐sensitive mitochondrial trifunctional protein deficiency presenting with episodic myopathy
Authors: Schwantje Marit , Ebberink Merel S. , Doolaard Mirjam , Ruiter Jos P. N. , Fuchs Sabine A. , Darin Niklas , Hedberg‐Oldfors Carola , Régal Luc , Donker Kaat Laura , Huidekoper Hidde H. , Olpin Simon , Cole Duncan , Moat Stuart J. , Visser Gepke , Ferdinandusse Sacha 
Published: April 2022

AbstractMitochondrial trifunctional protein (MTP) is involved in long‐chain fatty acid β‐oxidation (lcFAO). Deficiency of one or more of the enzyme activities as catalyzed by MTP causes generalized MTP deficiency (MTPD), long‐chain hydroxyacyl‐CoA dehydrogenase deficiency (LCHADD), or long‐chain ketoacyl‐CoA thiolase deficiency (LCKATD). When genetic variants result in thermo‐sensitive enzymes, increased body temperature (e.g. fever) can reduce enzyme activity and be a risk factor for clinical decompensation. This is the first description of five patients with a thermo‐sensitive MTP deficiency. Clinical and genetic information was obtained from clinical files. Measurement of LCHAD and LCKAT activities, lcFAO‐flux studies and palmitate loading tests were performed in skin fibroblasts cultured at 37°C and 40°C. In all patients (four MTPD, one LCKATD), disease manifested during childhood (manifestation age: 2–10 years) with myopathic symptoms triggered by fever or exercise. In four patients, signs of retinopathy or neuropathy were present. Plasma long‐chain acylcarnitines were normal or slightly increased. HADHB variants were identified (at age: 6–18 years) by whole exome sequencing or gene panel analyses. At 37°C, LCHAD and LCKAT activities were mildly impaired and lcFAO‐fluxes were normal. Remarkably, enzyme activities and lcFAO‐fluxes were markedly diminished at 40°C. Preventive (dietary) measures improved symptoms for most. In conclusion, all patients with thermo‐sensitive MTP deficiency had a long diagnostic trajectory and both genetic and enzymatic testing were required for diagnosis. The frequent absence of characteristic acylcarnitine abnormalities poses a risk for a diagnostic delay. Given the positive treatment effects, upfront genetic screening may be beneficial to enhance early recognition.
Comparison of pre–intestinal transplant and posttransplant sarcopenia and visceral adiposity measurements using computed tomography in the diagnosis of malnutrition during a nutrition‐focused physical examination
Authors: Dowhan Lindsay , Moccia Lisa , Remer Erick M. , Lyu Ruishen , Kou Lei , Steiger Ezra 
Published: April 2022

AbstractBackgroundRegistered dietitian nutritionists subjectively assess muscle loss as part of the nutrition‐focused physical examination (NFPE), using guidelines to standardize malnutrition diagnosis. Computed tomography (CT) scans provide an objective measure of skeletal muscle mass and abdominal wall and visceral adipose tissue and can be used to determine skeletal muscle loss.MethodsIn this retrospective review, our team compared muscle measurements including the psoas, paraspinal muscles, and abdominal wall muscle area at the level of the third lumbar vertebral body (using CT)—as well as visceral and subcutaneous adipose tissue measurements—before and after gut transplant with the malnutrition diagnosis found on the NFPE. We also examined the association between CT measurements and postoperative infection, length of stay, and mortality.ResultsForty‐two patients were included in the study. Adipose tissue measurements on CT analysis were significantly lower in the malnutrition group compared with those without malnutrition (P ≤ 0.05) in both the pretransplant and posttransplant groups. Skeletal muscle size measurements were not significantly associated with malnutrition, but when adjusted for patients’ height by calculating skeletal muscle index, an association between low skeletal muscle index scores and malnutrition diagnosis was found (P = 0.026). Pretransplant malnutrition diagnosis did not predict infection, length of stay, or mortality.ConclusionObjective assessment of subcutaneous adipose tissue by CT analysis was significantly correlated with the subjective assessment of malnutrition by NFPE in both pretransplant and posttransplant patients. Skeletal muscle index scores were significantly lower in pretransplant patients who were diagnosed with malnutrition.