bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineering Bilayer AlOx /YAlOx Dielectric Stacks for Hysteresis-Free Switching in Solution-Processed Metal-Oxide Thin-Film Transistors
Authors: Bolat Sami , Agiannis Evangelos , Yang Shih-Chi , Futscher Moritz H. , Aribia Abdesselam , Shorubalko Ivan , Romanyuk Yaroslav E. 
Published: January 2022

Solution processing and low-temperature annealing (T &lt; 300°C) of the precursor compounds promise low-cost manufacturing for future applications of flexible oxide electronics. However, thermal budget reduction comes at the expense of increased charge trapping residuals in the dielectric layers, which result in hysteretic switching of transistors. This work reports on a novel bilayer dielectric scheme combining aluminum oxide (AlOx) as a positive charge trapping insulator and yttrium aluminum oxide (YAlOx) as a negative charge trapping dielectric to obtain hysteresis free switching in the solution-processed metal-oxide thin-film transistors. Devices were processed at a thermal budget of 250°C, without an encapsulation layer. The presence of H+ and OH− in the AlOx were found responsible for the hysteresis in the switching, which was suppressed successfully with the thickness optimization of the YAlOx in the dielectric stack. Fabricated devices yield ON/OFF ratios of 106, sub-pA level gate leakage currents, a subthreshold swing of 150 mV/decade, and field-effect mobility of 1.5 cm2/V-sec.
Gut Microbial Signatures for Glycemic Responses of GLP-1 Receptor Agonists in Type 2 Diabetic Patients: A Pilot Study
Authors: Tsai Chih-Yiu , Lu Hsiu-Chen , Chou Yu-Hsien , Liu Po-Yu , Chen Hsin-Yun , Huang Meng-Chuan , Lin Chia-Hung , Tsai Chi-Neu 
Published: January 2022

BackgroundsGlucagon-like peptide-1 receptor agonist (GLP-1 RA) is probably one of more effective antidiabetic agents in treatment of type 2 diabetes mellitus (T2D). However, the heterogenicity in responses to GLP-1 RA may be potentially related to gut microbiota, although no human evidence has been published. This pilot study aims to identify microbial signatures associated with glycemic responses to GLP-1 RA.Materials and MethodsMicrobial compositions of 52 patients with T2D receiving GLP-1 RA were determined by 16S rRNA amplicon sequencing. Bacterial biodiversity was compared between responders versus non-responders. Pearson’s correlation and random forest tree algorithm were used to identify microbial features of glycemic responses in T2D patients and multivariable linear regression models were used to validate clinical relevance.ResultsBeta diversity significantly differed between GLP-1 RA responders (n = 34) and non-responders (n = 18) (ADONIS, P = 0.004). The top 17 features associated with glycohemoglobin reduction had a 0.96 diagnostic ability, based on area under the ROC curve: Bacteroides dorei and Roseburia inulinivorans, the two microbes having immunomodulation effects, along with Lachnoclostridium sp. and Butyricicoccus sp., were positively correlated with glycemic reduction; Prevotella copri, the microbe related to insulin resistance, together with Ruminococcaceae sp., Bacteroidales sp., Eubacterium coprostanoligenes sp., Dialister succinatiphilus, Alistipes obesi, Mitsuokella spp., Butyricimonas virosa, Moryella sp., and Lactobacillus mucosae had negative correlation. Furthermore, Bacteroides dorei, Lachnoclostridium sp. and Mitsuokella multacida were significant after adjusting for baseline glycohemoglobin and C-peptide concentrations, two clinical confounders.ConclusionsUnique gut microbial signatures are associated with glycemic responses to GLP-RA treatment and reflect degrees of dysbiosis in T2D patients.
Immune Dysfunctions of CD56neg NK Cells Are Associated With HIV-1 Disease Progression
Authors: Cao Wen-Jing , Zhang Xiao-Chang , Wan Lin-Yu , Li Qing-Yu , Mu Xiu-Ying , Guo An-Liang , Zhou Ming-Ju , Shen Li-Li , Zhang Chao , Fan Xing , Jiao Yan-Mei , Xu Ruo-Nan , Zhou Chun-Bao , Yuan Jin-Hong , Wang Sheng-Qi , Wang Fu-Sheng , Song Jin-Wen 
Published: January 2022

BackgroundPopulations of natural killer cells lacking CD56 expression [CD56neg natural killer (NK) cells] have been demonstrated to expand during human immunodeficiency virus (HIV)-1 infection. However, their phenotypic and functional characteristics have not been systematically analyzed, and their roles during disease progression remain poorly understood.MethodsIn this study, 84 donors, namely 34 treatment-naïve HIV-1-infected patients (TNs), 29 HIV-1-infected patients with successful antiretroviral therapy (ARTs), and 21 healthy controls (HCs), were enrolled. The phenotypic and functional characteristics of CD56neg NK cells were analyzed using single-cell RNA-sequencing (scRNA-seq) and flow cytometry. A potential link between the characteristics of CD56neg NK cells and the clinical parameters associated with HIV-1 disease progression was examined.ResultsThe frequency of the CD56neg NK cell population was significantly increased in TNs, which could be partially rescued by ART. Flow cytometry analyses revealed that CD56neg NK cells were characterized by high expression of CD39, TIGIT, CD95, and Ki67 compared to CD56dim NK cells. In vitro assays revealed reduced IFN-γ and TNF-α secretion, as well as decreased expression of granzyme B and perforin in CD56neg NK cells. In line with the data obtained by flow cytometry, scRNA-seq analysis further demonstrated impaired cytotoxic activities of CD56neg NK cells. Notably, a negative correlation was observed between CD39, CD95, and Ki67 expression levels in CD56neg NK cells and CD4+ T cell counts.ConclusionsThe results presented in this study indicate that the CD56neg NK cell population expanded in HIV-1-infected individuals is dysfunctional and closely correlates with HIV-1 disease progression.
Study of Brain Structure and Function in Chronic Mountain Sickness Based on fMRI
Authors: Bao Haihua , He Xin , Wang Fangfang , Kang Dongjie 
Published: January 2022

Objective: Headache and memory impairment are the primary clinical symptoms of chronic mountain sickness (CMS). In this study, we used voxel-based morphometry (VBM) and the amplitude of the low-frequency fluctuation method (ALFF) based on blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) to identify changes in the brain structure and function caused by CMS.Materials and Methods: T1W anatomical images and a resting-state functional MRI (fMRI) of the whole brain were performed in 24 patients diagnosed with CMS and 25 normal controls matched for age, sex, years of education, and living altitude. MRI images were acquired, followed by VBM and ALFF data analyses.Results: Compared with the control group, the CMS group had increased gray matter volume in the left cerebellum crus II area, left inferior temporal gyrus, right middle temporal gyrus, right insula, right caudate nucleus, and bilateral lentiform nucleus along with decreased gray matter volume in the left middle occipital gyrus and left middle temporal gyrus. White matter was decreased in the bilateral middle temporal gyrus and increased in the right Heschl's gyrus. Resting-state fMRI in patients with CMS showed increased spontaneous brain activity in the left supramarginal gyrus, left parahippocampal gyrus, and left middle temporal gyrus along with decreased spontaneous brain activity in the right cerebellum crus I area and right supplementary motor area.Conclusion: Patients with CMS had differences in gray and white matter volume and abnormal spontaneous brain activity in multiple brain regions compared to the controls. This suggests that long-term chronic hypoxia may induce changes in brain structure and function, resulting in CMS.
Stroke Telerehabilitation in Calabria: A Health Technology Assessment
Authors: Contrada Marianna , Arcuri Francesco , Tonin Paolo , Pignolo Loris , Mazza Tiziana , Nudo Giuseppe , Pignataro Maria Luigina , Quintieri Maria , Iozzi Antonella , Cerasa Antonio 
Published: January 2022

Introduction:Telerehabilitation (TR) is defined as a model of home service for motor and cognitive rehabilitation, ensuring continuity of care over time. TR can replace the traditional face-to-face approach as an alternative method of delivering conventional rehabilitation and applies to situations where the patient is unable to reach rehabilitation facilities or for low-income countries where outcomes are particularly poor. For this reason, in this study, we sought to demonstrate the feasibility and utility of a well-known TR intervention on post-stroke patients living in one of the poorest indebted regions of Italy, where the delivery of rehabilitation services is inconsistent and not uniform.Materials and Methods:Nineteen patients (13 male/6 female; mean age: 61.1 ± 8.3 years) with a diagnosis of first-ever ischemic (n= 14) or hemorrhagic stroke (n= 5), who had been admitted to the intensive rehabilitation unit (IRU) of the Institute S. Anna (Crotone, Italy), were consecutively enrolled to participate in this study. After the discharge, they continued the motor treatment remotely by means of a home-rehabilitation system. The entire TR intervention was performed (online and offline) using the Virtual Reality Rehabilitation System (VRRS) (Khymeia, Italy). All patients received intensive TR five times a week for 12 consecutive weeks (60 sessions, each session lasting about 1h).Results:We found a significant motor recovery after TR protocol as measured by the Barthel Index (BI); Fugl-Meyer motor score (FM) and Motricity Index (MI) of the hemiplegic upper limbs.Conclusions:This was the first demonstration that a well-defined virtual reality TR tool promotes motor and functional recovery in post-stroke patients living in a low-income Italian region, such as Calabria, characterized by a paucity of specialist rehabilitation services.
Grain-Based Dietary Background Impairs Restoration of Blood Flow and Skeletal Muscle During Hindlimb Ischemia in Comparison With Low-Fat and High-Fat Diets
Authors: Stafeev Iurii , Boldyreva Maria , Michurina Svetlana , Mamontova Elizaveta , Ratner Elizaveta , Menshikov Mikhail , Parfyonova Yelena 
Published: January 2022

Background: Among vascular pathologies associated with obesity, peripheral artery disease (PAD) occupies the important position. In clinical practice, nutritional interventions are recommended for patients with PAD. In this work, we investigated how the different dietary backgrounds affect the regeneration rate of ischemic hindlimb in mice.Methods: Male C57BL/6J mice were housed on three types of diet: low-fat (LFD), high-fat (HFD), and grain-based diet (GBD) for 13 weeks. Metabolic parameters including FBG level, ITT, and GTT were evaluated. The blood flow was assessed by laser Doppler scanning on 7, 14, and 21 days after hindlimb ischemia. Necrotic area of m.tibialis, macrophage infiltration, and angiogenesis/arteriogenesis were evaluated by histology. Glucose uptake in recovered skeletal muscle was analyzed using [3H]-2-deoxyglucose, and GLUT1 and GLUT4 expression were assessed by Western blotting.Results: In our work, we developed three experimental groups with different metabolic parameters: LFD with normal glucose metabolism, GBD with mild hyperglycemia, and HFD with impaired glucose tolerance. GBD-fed mice had a tendency to increase necrosis of m. tibialis and significantly higher macrophage infiltration than LFD and HFD groups. Moreover, GBD-fed mice had a trend to decreased blood flow recovery and significantly impaired arteriogenesis. Recovered skeletal muscle of GBD-fed mice had lower glucose uptake and decreased level of GLUT4 expression.Conclusion: Thus, we conclude that dietary background and metabolic status determine the rate of post-ischemic regeneration including angiogenesis, skeletal muscle recovery and metabolic activity. The most effective regeneration is supported by LFD, while the lowest rate of regeneration occurs on GBD.
Breast Cancer Classification Based on Tumor Budding and Stem Cell-Related Signatures Facilitate Prognosis Evaluation
Authors: Xiang Zhenxian , He Qiuming , Huang Li , Xiong Bin , Xiang Qingming 
Published: January 2022

BackgroundTumor budding (TB) is emerging as a prognostic factor in multiple cancers. Likewise, the stemness of cancer cells also plays a vital role in cancer progression. However, nearly no research has focused on the interaction of TB and tumor stemness in cancer.MethodsTissue microarrays including 229 cases of invasive breast cancer (BC) were established and subjected to pan-cytokeratin immunohistochemical staining to evaluate molecular expression. Univariate and multivariate analyses were applied to identify prognostic factors of BC, and the Chi-square test was used for comparison of categorical variables.ResultsHigh-grade TB was significantly associated with T stage, lymph node metastasis, tumor node metastasis (TNM) stage, epithelial-mesenchymal transition, and poor disease-free survival (DFS) of BC patients. We also found that the prognostic value of TB varied widely among different subtypes and subgroups. Cox regression analysis then showed that TB grade was an independent prognostic factor. Moreover, cancer stem cell (CSC) markers CD44 and ALDH1A1 were significantly higher in high-grade TB tumors. Consequently, patients were classified into high CSC score subgroup and low CSC score subgroups. Further research found that CSC scores correlated with clinicopathological features and DFS of BC patients. Based on TB grade and CSC scores, we classified BC patients into TBlow-CSCslow (type I), TBlow-CSCshigh (type II), TBhigh-CSCslow (type III), and TBhigh-CSCshigh (type IV) subgroups. Survival analysis showed that patients in the type I subgroup had the best DFS, whereas those in the type IV subgroup had the worst DFS. Finally, a TB-CSC-based nomogram for use in BC was established. The nomogram was well calibrated to predict the probability of 5-year DFS, and the C-index was 0.837. Finally, the area under the curve value for the nomogram (0.892) was higher than that of the TNM staging system (0.713).ConclusionThe combination of TB grade with CSC score improves the prognostic evaluation of BC patients. A novel nomogram containing TB grade and CSC score provides doctors with a candidate tool to guide the individualized treatment of cancer patients.
Maternal Sweeteners Intake Modulates Gut Microbiota and Exacerbates Learning and Memory Processes in Adult Male Offspring
Authors: de la Garza Ana Laura , Romero-Delgado Bianca , Martínez-Tamez Alejandra Mayela , Cárdenas-Tueme Marcela , Camacho-Zamora Bianka Dianey , Matta-Yee-Chig Daniel , Sánchez-Tapia Mónica , Torres Nimbe , Camacho-Morales Alberto 
Published: January 2022

Background: There is increasing evidence that gut microbiota in offspring is derived in part from maternal environment such as diet. Thus, sweeteners intake including caloric or non-caloric during perinatal period can induce gut dysbiosis and program the offspring to develop cognitive problems later in life.Objective: To determine the effect of maternal high-sweeteners intake during gestation and lactation on gut microbiota shifts in adult male offspring rats and the impact on cognitive dysfunction.Methods: Thirty-four male pups from dams fed standard diet (Control-C, n = 10), high-sucrose diet (HS-C, n = 11), high-honey diet (Ho-C, n = 8), and high-stevia diet (HSt-C, n = 5) were fed standard diet after weaning, and body weight and food intake were recorded once a week for 26 weeks. Learning and memory tests were performed at week 23 of life using the Barnes maze. Fecal samples from the breastfeeding and adulthood periods were collected and analyzed by sequencing the 16S rRNA V3-V4 region of gut microbiota.Results: Maternal high-sucrose and stevia diets programmed the male offspring, and changes in microbial diversity by Shannon index were observed after weaning (p &lt; 0.01). Furthermore, maternal high-stevia diet programming lasted into adulthood. The increase of Firmicutes abundance and the decrease in phylum Bacteroidetes were significant in HS-C and HSt-C groups. This led to an increase in the Firmicutes/Bacteroidetes index, although only in HS-C group was statistically significant (p &lt; 0.05). Of note, the downstream gram-negative Bacteroidales and the upregulation of the gram-positive Clostridiales abundance contribute to cognitive dysfunction.Conclusion: These results suggest that dams fed a high-sucrose and stevia diets during gestation and lactation favor a deficient memory performance in adult male offspring rats through shifts gut microbiota diversity and relative abundance at several taxa.
Impact of Sampling Time Variability on Tacrolimus Dosage Regimen in Pediatric Primary Nephrotic Syndrome: Single-Center, Prospective, Observational Study
Authors: Huang Lingfei , Wang Junyan , Yang Jufei , Zhang Huifen , Hu Yan , Miao Jing , Mao Jianhua , Fang Luo 
Published: January 2022

Background: Tacrolimus (TAC) is an important immunosuppressant for children with primary nephrotic syndrome (PNS). The relationship between sampling time variability in TAC therapeutic drug monitoring and dosage regimen in such children is unknown.Methods: In this single-center, prospective, observational study, we evaluated the sampling time variability, concentration error (CE), relative CE (RCE), and the impact of the sampling time on TAC dosage regimens in 112 PNS children with 188 blood samples. Nominal concentration (Cnom) at 12-h after last TAC dose was simulated based on observed concentration (Cobs) via previously published pharmacokinetic models, then CE and RCE were calculated. Inappropriate dosing adjustments resulting from deviated sampling time were evaluated based on a target Cnom of 5–10 ng/ml.Results: We found that 32 and 68% of samples were respectively collected early (2–180 min) and delayed (4–315 min). Furthermore, 24, 22, 22, and 32% of blood samples were drawn within deviations of ≤0.5, 0.5–1, 1–2, and &gt;2 h, respectively, and 0.3 ng/ml of CE and 6% RCE per hour of deviation occurred. Within a deviation of &gt;2 h, 25% of Cobs might result in inappropriate dosing adjustments. Early and delayed sampling might result in inappropriate dose holding or unnecessary dose increments, respectively, in patients with Cobs ∼ 5 ng/ml.Conclusions: Variable sampling time might lead to inappropriate dosing adjustment in a minority of children with PNS, particularly those with TAC Cobs ∼ 5 ng/ml collected with a deviation of &gt;2 h.
Biodistribution Study of Niosomes in Tumor-Implanted BALB/C Mice Using Scintigraphic Imaging
Authors: De Silva Leanne , Fu Ju-Yen , Htar Thet Thet , Wan Kamal Wan Hamirul Bahrin , Kasbollah Azahari , Muniyandy Saravanan , Chuah Lay-Hong 
Published: January 2022

The purpose of this work was to study the biodistribution of niosomes in tumor-implanted BALB/c mice using gamma scintigraphy. Niosomes were first formulated and characterized, then radiolabeled with Technetium-99 m (99mTc). The biodistribution of 99mTc-labeled niosomes was evaluated in tumor-bearing mice through intravenous injection and imaged with gamma scintigraphy. The labeled complexes possessed high radiolabeling efficiency (98.08%) and were stable in vitro (&gt;80% after 8 h). Scintigraphic imaging showed negligible accumulation in the stomach and thyroid, indicating minimal leaching of the radiolabel in vivo. Radioactivity was found mainly in the liver, spleen and kidneys. Tumor-to-muscle ratio indicated a higher specificity of the formulation for the tumor area. Overall, the formulated niosomes are stable both in vitro and in vivo, and show preferential tumor accumulation.
Microbiopsy Sampling for Examining Age-Related Differences in Skeletal Muscle Fiber Morphology and Composition
Authors: Hester Garrett M. , VanDusseldorp Trisha A. , Ha Phuong L. , Kiani Kaveh , Olmos Alex A. , Jabbari Melody , Kalladanthyil Shania , An SooBin , Bailly Alyssa R. , Dalton Benjamin E. , Bryantsev Anton L. 
Published: January 2022

Introduction: The increasingly popular microbiopsy is an appealing alternative to the more invasive Bergström biopsy given the challenges associated with harvesting skeletal muscle in older populations. Parameters of muscle fiber morphology and composition derived from the microbiopsy have not been compared between young and older adults.Purpose: The purpose of this study was to examine muscle fiber morphology and composition in young (YM) and older (OM) males using the microbiopsy sampling technique. A secondary aim was to determine if specific strength is associated with serum levels of C-terminal agrin fragment [CAF; an indicator of neuromuscular junction (NMJ) degradation].Methods: Thirty healthy, YM (n = 15, age = 20.7 ± 2.2 years) and OM (n = 15, age = 71.6 ± 3.9 years) underwent ultrasound imaging to determine whole-muscle cross-sectional area (CSA) of the vastus lateralis and rectus femoris as well as isometric and isokinetic (60°⋅s–1 and 180°⋅s–1) peak torque testing of the knee extensors. Microbiopsy samples of the vastus lateralis were collected from 13 YM and 11 OM, and immunofluorescence was used to calculate CSA and proportion of type I and type II fibers.Results: Peak torque was lower in OM at all velocities (p ≤ 0.001; d = 1.39–1.86) but only lower at 180°⋅s–1 (p = 0.003; d = 1.23) when normalized to whole-muscle CSA. Whole-muscle CSA was smaller in OM (p = 0.001; d = 1.34), but atrophy was not present at the single fiber level (p &gt; 0.05). Per individual, ∼900 fibers were analyzed, and type I fiber CSA was larger (p = 0.05; d = 0.94) in OM which resulted in a smaller type II/I fiber CSA ratio (p = 0.015; d = 0.95). CAF levels were not sensitive to age (p = 0.159; d = 0.53) nor associated with specific strength or whole-muscle CSA in OM.Conclusion: The microbiopsy appears to be a viable alternative to the Bergström biopsy for histological analyses of skeletal muscle in older adults. NMJ integrity was not influential for age-related differences in specific strength in our healthy, non-sarcopenic older sample.