bluuebunny/crossref_metadata_2025_split huggingface dataset:
Who Was at Risk for COVID-19 Late in the US Pandemic? Insights From a Population Health Machine Learning Model
Authors: Adeoye Elijah A. , Rozenfeld Yelena , Beam Jennifer , Boudreau Karen , Cox Emily , Scanlan James M. 
Published: September 2021

Abstract
Background: Notable discrepancies in vulnerability to COVID-19 infection have been identified between specific population groups and regions in the United States. The purpose of this study was estimate likelihood of COVID-19 infection using a machine-learning algorithm that can be updated continuously based on health care data.Methods: Patient records were extracted for all COVID-19 nasal swab PCR tests performed within the Providence St. Joseph Health system from February to October of 2020. Several different machine learning models were tested to evaluate effects of sociodemographic, environmental, and medical history factors on risk of initial COVID-19 infection.Results: A total of 316,599 participants were included in this study and approximately 7.7% (n = 24,358) tested positive for COVID-19. A gradient boosting model, LightGBM (LGBM), predicted risk of initial infection with an area under the receiver operating characteristic curve of 0.819. Factors that predicted infection were cough, fever, being a member of the Hispanic or Latino community, being Spanish speaking, having a history of diabetes or dementia, and living in a neighborhood with housing insecurity. Conclusion: A model trained on sociodemographic, environmental, and medical history data performed well in predicting risk of a positive COVID-19 test. This model could be used to tailor education, public health policy, and resources for communities that are at the greatest risk of infection.
High Expression of TTYH3 Predicts Poor Outcome in Hepatocellular Carcinoma
Authors: Gui Yonghui , Xu Yuanhong , Yang Peng 
Published: September 2021

Abstract
Objective Analyze the expression level of TTYH3 gene in liver cancer, promoter methylation, gene mutation, co-expression, Immune infiltration, protein interaction and overall survival by database mining. Methods We utilized the UALCAN, GEPIA, cBioPortal, Metascape, STRING, TIMER, TISIDB, and MEXPRESS databases to investigate the transcription level, genetic alteration, methylation, and biological function of TTYH3 in HCC patients, and its association with the occurrence, progress, prognosis, and immune cell infiltration in patients with HCC. Results Multiple databases have confirmed that the mRNA level of TTYH3 in liver cancer tissues is significantly higher than that in normal tissues. UALCAN and GEPIA confirmed that the overexpression of TTYH3 mRNA was associated with clinical stage, and the expression of TTYH3 mRNA increased with the increase of stage (P<0.05). Multiple databases confirmed that the overexpression of TTYH3 gene was associated with low survival rate (P<0.05). cBioPortal database analysis showed that TTYH3 gene mutation was associated with low survival rate and poor prognosis (P<0.05). GEPIA search for genes co-expressed with TTYH3. Timer database showed that TTYH3 was involved in inflammatory response and immune cell infiltration. Methylation data from MEXPRESS indicate significant probe level variation of CpG island methylation status of the gene TTYH3, which was associated with low survival rate (P<0.05), Moreover, we also found that the expression of TTYH3 was significantly correlated with tumor-infiltrating lymphocytes and immunomodulators, The STRING protein analysis network showed that TTYH3 may interact with BEST1, BEST2, BEST3, BEST4, ZnF467, CLCC1, GLRB, ANO1, IQCE, ANO2 and other proteins. Conclusion Through a variety of databases, it was found that TTYH3 was highly expressed in liver cancer, and the expression level was related to the survival and prognosis of liver cancer patients. Found TTYH3 involved in inflammation and immune cell infiltration and influence the outcomes in patients with liver cancer clinical, TTYH3 promoter methylation of meaningful expression differences in liver cancer, the co-expressed genes, proteins interaction can be in-depth study, as well as TTYH3 gene and the relationship between the liver cancer, for the prognosis of liver cancer biomarkers and therapeutic targets.
Plasma Kynurenine Level is Associated With Left DLPFC Activity and Can Predict Treatment Response in Major Depressive Disorder
Authors: Kamishikiryo Toshiharu , Okada Go , Itai Eri , Masuda Yoshikazu , Yokoyama Satoshi , Takamura Masahiro , Fuchikami Manabu , Yoshino Atsuo , Mawatari Kazuaki , Numata Shusuke , Takahashi Akira , Ohmori Tetsuro , Okamoto Yasumasa 
Published: September 2021

Abstract
To establish treatment response biomarkers that reflect the pathophysiology of depression, it is important to use an integrated set of features that are promising as biomarkers. This study aimed to determine the relationship between blood metabolites related to treatment response to escitalopram and regional brain activity at rest and to find the characteristics of depression that respond to treatment. Blood metabolite levels and resting brain activity were measured in patients with depression (N = 65) before and after 6 weeks treatment with escitalopram and healthy controls (N = 36). Thirty-two patients (49.2%) showed clinical response (>50% reduction in Hamilton Rating Scale for Depression score) and were classified as Responders, and the remaining 33 patients were classified as Nonresponders. Pretreatment plasma kynurenine level and fractional amplitude of low-frequency fluctuations (fALFF) of the left dorsolateral prefrontal cortex (DLPFC) were lower in Responders, and their elevations after treatment were correlated with improvement in symptoms. Moreover, fALFF of the left DLPFC was significantly correlated with plasma kynurenine level in pretreatment patients with depression and healthy controls. Decreased kynurenine level and resting-state regional brain activity of the left DLPFC may be involved in the pathophysiology of depression in response to escitalopram treatment.
Genome-Wide Identification and Characterization of The MADS-Box Gene Family and Its Expression in The Various Developmental Stage and Stress Conditions in Foxtail Millet (Setaria Italica)
Authors: Lai Dili , Yan Jun , He Ailing , Xue Guoxing , Yang Hao , Feng Liang , Wei Xiaobao , Li Long , Xiang Dabing , Ruan Jingjun , Fan Yu , Cheng Jianping 
Published: September 2021

Abstract
Foxtail millet (Setaria italica) is rich in nutrients and extremely beneficial to human health. We identified and comprehensively analyzed 89 MADS-box genes in the foxtail millet genome. According to the classification of MADS-box genes in Arabidopsis thaliana and rice, the SiMADS-box genes were divided into M-type (37) and MIKC-type (52). During evolution, the differentiation of MIKC-type MADS-box genes occurred before that of monocotyledons and dicotyledons. The SiMADS-box gene structure has undergone much differentiation, and the number of exons in the MIKC-type subfamily is much greater than that in the M-type subfamily. Analysis of gene duplication events revealed that MIKC-type MADS-box gene fragment duplication accounted for the vast majority of gene duplication events, and MIKC-type MADS-box genes played a major role in the amplification of SiMADS-box genes. Collinearity analysis showed highest collinearity between foxtail millet and maize MADS-box genes. Analysis of tissue-specific expression showed that SiMADS-box genes are highly expressed throughout the grain-filling process. Expression analysis of SiMADS-box genes under eight different abiotic stresses revealed many stress-tolerant genes, with induced expression of SiMADS33 and SiMADS78 under various stresses warranting further attention. Further, some SiMADS-box proteins may interact to cope with external stress. This study provides insights for MADS-box gene mining and molecular breeding of foxtail millet in the future.
Probing Elastic Anisotropy of Human Skin in Vivo With Light Using Non-Contact Acoustic Micro-Tapping OCE and Polarization-Sensitive OCT
Authors: Kirby Mitchell , Tang Peijun , Liou Hong-Cin , Kuriakose Maju , Pitre John J. , Pham Tam N. , Ettinger Russell , Wang Ruikang , O’Donnell Matthew , Pelivanov Ivan 
Published: September 2021

Abstract
Skin broadly protects the human body from undesired factors such as ultraviolet radiation and abrasion and helps conserve body temperature and hydration. Skin’s elasticity and its level of anisotropy are key to its aesthetics and function. Currently, however, treatment success is often speculative and subjective, and is rarely based on skin’s elastic properties because there is no fast and accurate non-contact method for imaging of skin’s elasticity. Here we report on a non-contact and non-invasive method to image and characterize skin’s elastic anisotropy. It combines acoustic micro-tapping optical coherence elastography (AmT-OCE) with a nearly incompressible transversely isotropic (NITI) model to quantify skin’s elastic moduli. In addition, skin sites were imaged with polarization sensitive optical coherence tomography (PS-OCT) to help define the fiber orientation. Forearm skin areas were investigated in five volunteers. Results clearly demonstrate elastic anisotropy of skin in all subjects. AmT-OCE has distinct advantage over competitive techniques because it provides objective, quantitative characterization of skin’s elasticity without contact, which opens the door for broad translation into clinical use. Finally, we demonstrate that a combination of multiple OCT modalities (structural OCT, OCT angiography, PS-OCT and AmT-OCE) may provide rich information about skin and can be used to characterize scaring.
A Single-center Prospective Study on the Efficacy of Nivolumab Against Platinum-sensitive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Authors: Okamoto Isaku , Tsukahara Kiyoaki , Sato Hiroki 
Published: September 2021

Abstract
Nivolumab, an immune checkpoint inhibitor, reportedly benefits patients with platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC). However, platinum-sensitive R/M-HNSCC has not yet been studied. Hence, this prospective study evaluated the efficacy and safety of nivolumab in patients with platinum-sensitive R/M-HNSCC. This prospective single-arm study was conducted in a single institution in Japan. Patients with platinum-sensitive R/M-HNSCC (defined as head and neck cancer that recurred or metastasized at least 6 months after platinum-based chemotherapy or chemoradiotherapy) were enrolled. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), overall response rate (ORR), immune-related adverse events (irAEs), and quality of life (QOL). This study was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN000031324). Twenty-two patients with platinum-sensitive R/M-HNSCC were enrolled. The median OS was 17.4, and the 1-year OS rate was 73%. The median PFS was 9.6 months, and the 1-year PFS rate was 48%. The ORR was 36%. In total, 16 irAEs were recorded in 12 patients; however, no grade 4 or 5 irAEs were observed. The QOL assessments revealed that nivolumab did not decrease the QOL of patients. Nivolumab is effective against platinum-sensitive R/M-HNSCC with acceptable safety.
Effect of Transverse Magnetic Field On Microstructure And Mechanical Properties of Ti-6Al-4V Manufactured By Laser-MIG Hybrid Welding
Authors: Yue Chen , Geng Shaoning , Jiang Ping , Yin Annan 
Published: September 2021

Abstract
In this paper, the external transverse magnetic field is used to assist the laser-MIG hybrid welding for Ti-6Al-4V (TC4). The microstructure and mechanical properties such as microhardness and tensile properties of the weld joints under 24 mT external magnetic field (EMF) and the referring weld joint without EMF are investigated and discussed. Results show that transfer layer (TL) performs the lowest microhardness in the weld seam and tensile specimens fail in this area for the referring weld joint without EMF, which indicates the TL is the weakest zone in the weld seam. The mechanical properties of weld seam improve significantly under 24 mT EMF, which average microhardness in TL increases 9.3% and failure stress of tensile specimens improve by 16.7%, whilst a mixed fracture mode is operative in the fracture surfaces. The research reveals the elementary microstructure of TC4 laser-MIG hybrid welding is in correlation to welding heat input under the influence of EMF.
Current Status and Trend of Clinical Development of Orphan Drugs in China
Authors: Xiang Ziling , Jiang Wengao , Yan Bo , Jiang Junhao , Zheng Hang 
Published: September 2021

Abstract
Background:Rare diseases have been increasingly recognized as medical and healthy burden worldwide, a growing demand for the development of orphan drugs emerges subsequently. Therefore, it is of great interest for both the regulatory agency and pharmaceutical companies to keep tract on the clinical orphan drug development in China.Objective and Method:This study aims to reveal the current situation and trend of the clinical development of orphan drugs in China, based on the data collected from the Platform for Drug Clinical Trials and Information Registration（http://www.chinadrugtrials.org.cn）of China Food and Drug Administration, dating from 2013 to March 8, 2021.Results:A total of 246 clinical trials for orphan drugs are extracted from the Platform, covering 22 rare diseases and 90 drugs. Among the 22 rare diseases, 3 (14 %) have more than 50 trials each , 17 (77%) had less than10 trials, and 10 (46%) only with one trial. Among 90 orphan drugs, 60 (67%) were chemical drugs, and 30 (33 %) were biological products. In addition, international multi-center trials accounts for nearly 10% of the total trials. The number of the trials with the Data Monitoring Security Committee (DMC) is 25 (10%) and the number of the trials with the trial injury insurance for subjects is 154 (63%). Furthermore, more than half of the total trials are carried in east (333, 30%) and north China (298, 27%), whereas a small portion are in the northwest (62, 6%) and northeast china (45, 4%).Conclusions:The clinical development of orphan drugs for rare diseases in China has made some progress in the passing decades. However, a couple of critical issues still need to be addressed, such as unmet needs for some rare diseases, low coverage of insurance and DMC, and uneven distribution of medical resources for clinical researches. Recommendations are put forward accordingly, which can provide improvement goals for policy makers and stakeholders involved in drug development for rare diseases.
Clinical and Quality of Life Outcomes of a Combined Synthetic Scaffold and Autogenous Tissue Graft Procedure for Articular Cartilage Repair in the Knee
Authors: Rosa Fernando Martins , Fernandes Julio Cesar , Delisle Josée , Ranger Pierre , Albano Mauro Batista , Filho Edmar Stieven 
Published: September 2021

Abstract
Background: Injuries to the articular cartilage of the knee often fail to heal properly, due to the hypocellular and avascular nature of this tissue. Subsequent disability can limit participation in sports and decrease quality of life. Subchondral bone perforations are used for the treatment of small defects. Larger lesions filling out the central portion becomes difficult, and scaffolds can be used as adjuvants, providing a matrix onto which the defect can be filled in completely and also autogenous cartilage grafts can be combined, acting as an inducer and improving healing quality, all in a single procedure.Methods: Evaluate the clinical and quality of life outcomes of patients with articular cartilage lesions of the knee undergoing repair via a microfracture technique combined with a synthetic scaffold and autogenous cartilage graft, with transosseous sutures and fibrin glue fixation, at 12 months of follow-up. Secondarily, assess whether combined procedures, previous surgical intervention, traumatic aetiology, lesion location, and age affect outcomes. Observational study of adult patients (age 18–66 years) with symptoms consistent with chondral or osteochondral lesions, isolated or multiple, ICRS grade III/IV, 2–12 cm2 in size. Patients with corrected angular deviations or instabilities were included. Those with BMI > 40 kg/m2, prior total or subtotal (> 30%) meniscectomy, second-look procedures, and follow-up < 6 months were excluded. Pain (VAS), physical activity (IKDC), osteoarthritis (WOMAC), and general quality of life (SF-36) were assessed.Results: 64 procedures were included, comprising 60 patients. There was significant improvement (P < 0.05) in VAS (5.92 to 2.37), IKDC score (33.44 to 56.33), and modified WOMAC score (53.26 to 75.93) after surgery. The SF-36 showed significant improvements in the physical and mental domains (30.49 to 40.23 and 46.43 to 49.84 respectively; both P < 0.05).Conclusions: Combination of microfractures, autogenous crushed cartilage graft, synthetic scaffold, and transosseous sutures with fibrin glue provides secure fixation for treatment of articular cartilage lesions of the knee. At 12-month follow-up, function had improved by 20 points on the IKDC and WOMAC, and quality of life by 10 points on the SF-36. Age > 45 years had a negative impact on outcomes.
Potential Neuroprotective Effect of Nanomicelle Curcumin on Learning and Memory Functions Following Subacute Exposure to Bisphenol a in Adult Male Rats
Authors: Fallahnezhad Somaye , Ghorbani-Taherdehi Faezeh , Nadim Azade , Kafashzadeh Mehrnaz , Kafashzadeh Mehrnoosh , Gorji-Valokola Mahmoud 
Published: September 2021

Abstract
ObjectiveBisphenol A (BPA) is an endocrine-disrupting chemical that widely used in plastics production. It can influence on the brain tissue. Curcumin has a strong protective activity against brain disorders. The purpose of this study was to evaluate the protective effect of nanomicelle curcumin (NmCur) on BPA-induced learning and memory disorders in rats.Material and methodsIn this study, after determining the dose of BPA, rats were randomly divided into 8 groups (8 rats in each group); sesame oil, dextrose 5%, sesame oil + dextrose 5%, NmCur (50 mg/kg), BPA (50 mg/kg), and 50 mg/kg BPA plus 10, 25, or 50 mg/kg NmCur, respectively. All materials administered via gavage. Behavioral tests were estimated by shuttle-box, open-field, and Morris water maze devices. Then, stress oxidative, pro-inflammatory cytokines, oxidative stress-scavenging enzymes levels, as well as expression of MAPK proteins, glutamate receptors, and memory-related proteins were determined in the hippocampus and cortex tissues. ResultsBPA significantly increased expression of ROS, MDA, TNF-α, IL-6, IL-1β, SOD, GST, p-P38, and p-JNK; however, considerably decreased GSH, GPx, GR, CAT, p-AKT, p-ERK1/2 levels. In addition, it down regulated expression of p-NR1, p-NR2A, p-NR2B, p-GluA1, BDNF, and p-CREB in rat cortex and hippocampus tissues. BPA significantly also changed behavioral activity. Conversely, BPA (50 mg/kg) plus NmCur (25 and 50 mg/kg) significantly reversed all BPA-induced adverse effects. ConclusionThe results of this study support that nanomicelle curcumin exhibited preventive effects against neurotoxicity and learning and memory impairment induced by subacute exposure to bisphenol A.
Holotoxin Disassembly by Protein Disulfide Isomerase Is Less Efficient for Escherichia Coli Heat-labile Enterotoxin Than Cholera Toxin
Authors: Serrano Albert , Guyette Jessica L. , Heim Joel B. , Taylor Michael , Cherubin Patrick , Krengel Ute , Teter Ken , Tatulian Suren 
Published: September 2021

Abstract
Cholera toxin (CT) and Escherichia coli heat-labile enterotoxin (LT) are structurally similar AB5-type protein toxins. They move from the cell surface to the endoplasmic reticulum where the A1 catalytic subunit is separated from its holotoxin by protein disulfide isomerase (PDI), thus allowing the dissociated A1 subunit to enter the cytosol for a toxic effect. Despite similar mechanisms of toxicity, CT is more potent than LT. The difference has been attributed to a more stable domain assembly for CT as compared to LT, but this explanation has not been directly tested and is arguable as toxin disassembly is an indispensable step in the cellular action of these toxins. We show here that PDI disassembles CT more efficiently than LT, which provides a possible explanation for the greater potency of the former toxin. Furthermore, direct examination of CT and LT domain assemblies found no difference in toxin stability. Using novel analytic geometry approaches, we provide a detailed characterization of the positioning of the A subunit with respect to the B5 pentamer and demonstrate significant differences in the interdomain architecture of CT and LT. Protein docking analysis further shows that these global structural differences result in distinct modes of PDI-toxin interactions. Our results highlight previously overlooked structural differences between CT and LT that provide a new molecular explanation for the PDI-assisted disassembly and differential potency of these toxins.
Characteristic Analysis and Electrical Conductivity of Graphene and Graphene-Nanosilver Prepared by Electrical Spark Discharge Method
Authors: Tseng Kuo-Hsiung , Yeh Chu-Ti , Ku Hsueh-Chien , Tien Der-Chi , Stobinski Leszek 
Published: September 2021

Abstract
This study used an electric discharge machine (EDM) to perform the electrical spark discharge method (ESDM) to prepare a graphene colloid and a graphene-Ag colloid. The characteristic wavelengths of graphene, and graphene-Ag are both 262 nm. They had the properties of high dispersion and are unlikely to aggregate. The XRD patterns of graphene and graphene-Ag are typical carbon diffraction peak angles and crystal orientations. Graphene-Ag in DW can increase the Raman signal intensity of graphene. Regarding the graphene colloid and graphene-Ag colloid, their average sheet resistance values are 0.0329 MΩ/sq and 0.00136 MΩ/sq, respectively. Moreover, when AgNPs composited with graphene layers, the average sheet resistance is only 1/24 that of graphene layers, indicating that graphene-Ag has superior conductivity.
Thin Flexible Lab-on-a-Film for Impedimetric Sensing in Biomedical Applications
Authors: Farooq Amina , Hayat Fezan , Zafar Sobia , Butt Nauman Zafar 
Published: September 2021

Abstract
Microfluidic cytometers based on coulter principle have recently shown a great potential for point of care biosensors for medical diagnostics. Here, we explore the design of an impedimetric microfluidic cytometer on flexible substrate. Two coplanar microfluidic geometries are compared to highlight the sensitivity of the device to the microelectrode positions relative to the detection volume. We show that the microelectrodes surface area and the geometry of the sensing volume for the cells strongly influence the output response of the sensor. Reducing the sensing volume decreases the pulse width but increases the overall pulse amplitude with an enhanced signal-to-noise ratio (~max. SNR=38.78dB). For the proposed design, the SNR was adequate to enable good detection and differentiation of 10 µm diameter polystyrene beads and leukemia cells (~6-21 µm). Also, a systematic approach for irreversible & strong bond strength between the thin flexible surfaces that make up the biochip is explored in this work. We observed the changes in surface wettability due to various methods of surface treatment can be a valuable metric for determining bond strength. We observed permanent bonding between microelectrode defined polypropylene surface and microchannel carved PDMS due to polar/silanol groups formed by plasma treatment and consequent covalent crosslinking by amine groups. These experimental insights provide valuable design guidelines for enhancing the sensitivity of coulter based flexible lab-on-a-chip devices which have a wide range of applications in point of care diagnostics.