Miracle-dz/UniFAR-FTUs huggingface dataset:
A Novel DNA Repair Gene Signature for Immune Checkpoint Inhibitor-Based Therapy in Gastric Cancer

Gastric cancer is a heterogeneous group of diseases with only a fraction of patients responding to immunotherapy. The relationships between tumor DNA damage response, patient immune system and immunotherapy have recently attracted attention. Accumulating evidence suggests that DNA repair landscape is a significant factor in driving response to immune checkpoint blockade (ICB) therapy. In this study, to explore new prognostic and predictive biomarkers for gastric cancer patients who are sensitive and responsive to immunotherapies, we developed a novel 15-DNA repair gene signature (DRGS) and its related scoring system and evaluated the efficiency of the DRGS in discriminating different molecular and immune characteristics and therapeutic outcomes of patients with gastric adenocarcinoma, using publicly available datasets. The results demonstrated that DRGS high score patients showed significantly better therapeutic outcomes for ICB compared to DRGS low score patients (p < 0.001). Integrated analysis of multi-omics data demonstrated that the patients with high DRGS score were characteristic of high levels of anti-tumor lymphocyte infiltration, tumor mutation burden (TMB) and PD-L1 expression, and these patients exhibited a longer overall survival, as compared to the low-score patients. Results obtained from HPA and IHC supported significant dysregulation of the genes in DRGS in gastric cancer tissues, and a positive correlation in protein expression between DRGS and PD-L1. Therefore, the DRGS scoring system may have implications in tailoring immunotherapy in gastric cancers. A preprint has previously been published (Yuan et al., 2021).
Influence of Hyperglycaemia and CRP on the Need for Mechanical Ventilation in Guillain-Barré Syndrome

Objectives Elevated blood glucose and CRP (C-reactive protein) are usually related to a worsened clinical outcome in neurological diseases. This association in Guillain-Barré syndrome (GBS) has been studied rarely. We tried to analyse if hyperglycaemia and CRP at admission may influence the outcome of GBS, including mechanically ventilated (MV) patients. Methods We retrospectively studied 66 patients (40 males, 19–93 years, average 56 years) without diabetes mellitus and free of corticoid treatment, who fulfilled the clinical criteria for diagnosis of GBS. Hyperglycaemia (the level of fasting plasma glucose, FPG) was defined as blood glucose level >5.59 mmol/L according to our laboratory. CRP >5 mg/L was considered as an abnormally elevated value. Results At admission, 32 GBS patients (48%) had hyperglycaemia according to FPG level. A severe form of GBS (>4 according to Hughes GBS scale) was observed in 17 patients (26%); and 8 of them (47%) had hyperglycaemia. Fourteen patients (21%) were MV, and in 10 of them (71%) hyperglycaemia was present. CRP was significantly increased in MV patients. The linear model revealed a significant relationship between CRP and glycemia (p = 0.007) in subjects without MV (p = 0.049). In subjects with MV the relationship was not significant (p = 0.2162, NS). Conclusion In the acute phase of GBS at admission, hyperglycaemia and higher CRP occur relatively frequently, and may be a risk factor for the severity of GBS. Stress hyperglycaemia due to impaired glucose homeostasis could be one explanation for this condition.
Late-Onset Calorie Restriction Improves Lipid Metabolism and Aggravates Inflammation in the Liver of Old Wistar Rats

Aging is a progressive process that could disturb metabolic homeostasis in the liver via ectopic lipid accumulation, oxidative stress, and deterioration of inflammatory response. Although calorie restriction (CR) is recognized as beneficial for life span and health span prolongation, it is still unclear how late-onset CR, characterized by late beginning and short duration, affects age-related processes. The aim of this study was to examine how late-onset CR-induced metabolic adjustments impact lipid status and inflammation in the liver of old rats. The experiments were conducted on aging male Wistar rats fed ad libitum (AL) or exposed to late-onset CR (60% of AL daily intake) from 21st to 24th month. The results showed that late-onset CR reduces body weight, visceral adipose tissue and liver mass, and triglyceride levels when compared to old animals on AL diet. The ameliorating effects of CR on lipid metabolism include increased activity of AMP-activated protein kinase, suppressed de novo fatty acid synthesis, stimulated β-oxidation, decreased lipotoxicity, and limited triglyceride synthesis and packaging in the liver. Restricted diet regime, however, does not improve expression of antioxidant enzymes, although it leads to progression of age-related inflammation in the liver, partially through lower corticosterone concentration and decreased activation of glucocorticoid receptor. In conclusion, late-onset CR is able to restore age-related imbalance of lipid metabolism in the liver, but has a negative impact on hepatic inflammatory status, implying that the type of diet for older individuals must be balanced and chosen carefully with appropriate duration and start point.
Mechanisms and Trends of Guaiacol Hydrodeoxygenation on Transition Metal Catalysts

Understanding the mechanisms of guaiacol’s catalytic hydrodeoxygenation (HDO) is essential to remove the oxygen excess in bio-oils. The present work systematically examines guaiacol’s HDO mechanisms to form benzene on six transition metal (TM) catalysts using density functional theory calculations. The results suggested a preferable Caryl−O bond scission on Ni (111) and Co (0001), whereas on Fe (110), the Caryl–OH bond scission is the most likely pathway. The C−O scission on Pd (111) and Pt (111) is not energetically feasible due to their high activation barriers and endothermic behaviour. Fe (110) also demonstrated its high oxophilic character by challenging the desorption of oxygenated products. A detailed analysis concludes that Co (0001) and Ni (111) are the most favourable in breaking phenolic compounds’ C−O type bonds. Brønsted-Evans-Polanyi (BEP) and transition state scaling (TSS) models were implemented on the catalytic results to derive trends and accelerate the catalyst design and innovation. TSS demonstrated a reliable trend in defining dissociation and association reaction energies. The phenyl ring-oxo-group and the metal-molecule distances complement the catalysts’ oxophilicity as selectivity descriptors in the HDO process.
Weathering of Chlorite Illite Deposits in the Hyperarid Qaidam Basin: Implications to Post-Depositional Alteration on Martian Clay Minerals

Chlorite is the second-most common class of clay minerals on the Martian surface and has been found to coexist with illite in some regions. Although previous studies have paid much attention to the formation of this assemblage, the post-depositional evolution cannot be neglected because the aqueous activities may alter the mineral assemblage and distribution. Here, we report on the post-depositional weathering of lacustrine-fluvial deposits collected from yardangs and dune-covering lake beds in the western Qaidam Basin, one of the largest and highest terrestrial Mars analogs. Mineralogical analysis shows that Fe-clinochlore and illite are the main clay components deposited as detrital particles. Electron microscopic observations of small rusty concretions from yardang deposits revealed that iron was released from clinochlore and formed ferrihydrite in fractures. We suggest that the activities of ephemeral waters after the deposition provide the major source of water that influences the migration of Fe in a long-lasting hyperarid climate. A similar iron-releasing mechanism could have occurred in Nili Fossae on Mars because multiple aqueous activities have shaped the terrains where chlorite illite deposits were identified by orbital near-infrared reflectance spectroscopy. Thus, reconstruction of the aqueous history of ancient Mars from surface minerals requires consideration of post-depositional processes, since groundwater/meteoric water may continuously interact with clay mineral-bearing deposits on Mars after their formation.
Influence of Dust Aerosols on Snow Cover Over the Tibetan Plateau

Dust in the atmosphere and snow on the Tibetan Plateau (TP) remarkably influence the Asian climate, which can influence snow cover by changing radiative forcing. In this study, we investigated the spatial and temporal distributions of dust and snow cover over the TP from 2009 to 2018 and estimated the relative contributions of atmospheric dust and dust-on-snow to the change in snow cover over the northern TP through the use of reanalysis datasets and satellite retrievals. The results show that the high and low centers of aerosol and dust aerosol optical depth (AOD) are roughly similar. Dust concentrations over the TP generally decrease from north to south and from west to east, showing decreasing trends in the winter half-year (December to May). The correlation coefficients between the dust concentration and snow cover over the northern TP are −0.6 in spring. Dust in the atmosphere and on snow over the TP could significantly influence snow cover by changing the radiative forcing, and the influence of dust deposited on snow is greater than that in the atmosphere. Atmospheric dust reduces the surface net solar radiation by −3.84 W m−2 by absorbing shortwave radiation, decreasing the surface temperature by −2.27°C, and finally increasing the snow cover by 1.04%. However, dust deposited on snow can decrease the surface albedo by −0.004 by reducing the surface optical properties, induce surface warming at 0.42°C, and reduce snow cover by −2.00% by rapid snowmelt in the northern TP.
Impedance-Based Phenotypic Readout of Transporter Function: A Case for Glutamate Transporters

Excitatory amino acid transporters (EAAT/SLC1) mediate Na+-dependent uptake of extracellular glutamate and are potential drug targets for neurological disorders. Conventional methods to assess glutamate transport in vitro are based on radiolabels, fluorescent dyes or electrophysiology, which potentially compromise the cell’s physiology and are generally less suited for primary drug screens. Here, we describe a novel label-free method to assess human EAAT function in living cells, i.e., without the use of chemical modifications to the substrate or cellular environment. In adherent HEK293 cells overexpressing EAAT1, stimulation with glutamate or aspartate induced cell spreading, which was detected in real-time using an impedance-based biosensor. This change in cell morphology was prevented in the presence of the Na+/K+-ATPase inhibitor ouabain and EAAT inhibitors, which suggests the substrate-induced response was ion-dependent and transporter-specific. A mechanistic explanation for the phenotypic response was substantiated by actin cytoskeleton remodeling and changes in the intracellular levels of the osmolyte taurine, which suggests that the response involves cell swelling. In addition, substrate-induced cellular responses were observed for cells expressing other EAAT subtypes, as well as in a breast cancer cell line (MDA-MB-468) with endogenous EAAT1 expression. These findings allowed the development of a label-free high-throughput screening assay, which could be beneficial in early drug discovery for EAATs and holds potential for the study of other transport proteins that modulate cell shape.
Intraseasonal Drivers of the 2018 Drought Over São Paulo, Brazil

Dry conditions occurred over São Paulo state (southeastern Brazil) from February to July 2018, causing the driest semester in 35 years. Socioeconomic impacts included a record number of fire spots, most adverse conditions to pollutant dispersion in 3 years and the winter's lowest water reservoirs stored volume in 17 years. This paper discusses climate drivers to the onset and persistence of the dry conditions, with special attention to the intraseasonal forcing. Barotropic atmospheric circulations forced by the intraseasonal Pacific-South America teleconnection pattern, embedded in the lower frequency setup of the Pacific Decadal Oscillation and the Atlantic Multidecadal Oscillation, were identified as main large-scale forcings to reduce precipitation. Drought evolution was modulated by other intraseasonal drivers such as the Madden Julian, Antarctic and 10–30 days Oscillations. A break in the 6-month dry condition, in March 2018, highlighted the important role of such oscillations in determining precipitation anomalies over SP. Results show that intraseasonal phenomena and their interactions control drought characteristics such as magnitude, persistence and spatial distribution within a setup determined by lower-frequency oscillations. The intraseasonal timescale seems to be key and must be considered for a complete description and understanding of the complex drought evolution process in São Paulo.
Self-Concept With Cross-Cultural Perspective: 36–72-Month-Old Preschool Children in Turkey and Germany

Children attending preschool education in Turkey and Germany have different cultural environments and education systems. This study aimed at investigating the self-concept of 36–72- month-old preschool children in Turkey, a country with a collectivist culture, and Germany, a country with an individualistic culture. Participants were 433 children (234 female, 199 male) from Turkey and 206 children (102 female, 109 male) from Germany. Three dimensions of self-concept were measured: ability-based, social, and physical. The Self-Concept Questionnaire for Children (Preschool Version) was used for data collection. This process lasted about 5 months. Country (Turkey vs. Germany) and sex (male vs. female) of the child were analyzed as independent variables, and the three dimensions of self-concept (i.e., ability-based, social, and physical) were analyzed as dependent variables. As normality assumption was not met for the subgroups, the Mann–Whitney U test was applied for statistical analysis. Results showed significant differences between children from Turkey and children from Germany in two self-concept dimensions (i.e., ability-based and physical). It was determined that there were no differences between the two countries in social self-concept. It was also determined that there were differences in the ability-based self-concept dimension in 36–72-month-old children depending on gender in Turkey, in favor of male children. On the other hand, it was determined that there were no differences depending on gender in any of the self-concept dimensions in Germany. It was concluded that culture was a factor leading to differentiation in some dimensions of preschool children’s self-concept.
Re-Visiting the Role of Education on Poverty Through the Channel of Financial Inclusion: Evidence From Lower-Income and Lower-Middle-Income Countries

For attaining sustainable economic development in the lower and lower-middle-income nations, the role of poverty reduction has been critically addressed along with the economic determents that manage poverty level which has accelerated the economic progress by ensuring the higher performance of other macrovariables including FDI inflows, financial development, trade openness, and human capital accumulation. The purpose of this study was to evaluate the role of education and financial inclusion in poverty reduction in lower and lower-middle-income countries for the period 1995–2018, with a panel of 68 nations. The study applied several econometrical tools, including a cross-sectional dependency test (CDS), panel unit root test, panel cointegration test, generalized methods of moment (GMM), and system-GMM. The CDS results confirmed the sharing of typical dynamics in research units. The test of stationarity detected variables was integrated after the first difference. A panel cointegration test documented the long-run association between education, financial inclusion, and poverty. The study documented that government investment in education positively assists poverty reduction, implying a negative association between them. Furthermore, the inclusion of the population into the formal financial system expedited the poverty reduction process that has access to formal financial benefits allowing earning opportunities and higher purchasing power, eventually supporting an increased standard of living. Directional causality tests revealed feedback hypothesis holds in explaining the nexus between education, financial inclusion, and poverty, i.e., [ED←→Poverty; FI←→Poverty]. For policy reform and restructuring, it is essential to pay considerable attention to development in education and access to the formal financial system because progress in education and finance has positive spillover effects on the aggregated economy.
Temperature and Growth Selection Effects on Proliferation, Differentiation, and Adipogenic Potential of Turkey Myogenic Satellite Cells Through Frizzled-7-Mediated Wnt Planar Cell Polarity Pathway

Satellite cells (SCs) are a heterogeneous population of multipotential stem cells. During the first week after hatch, satellite cell function and fate are sensitive to temperature. Wingless-type mouse mammary tumor virus integration site family/planar cell polarity (Wnt/PCP) signaling pathway is significantly affected by thermal stress in turkey pectoralis major (p. major) muscle SCs. This pathway regulates the activity of SCs through a frizzled-7 (Fzd7) cell surface receptor and two intracellular effectors, rho-associated protein kinase (ROCK) and c-Jun. The objective of the present study was to determine the effects of thermal stress, growth selection, and the Fzd7-mediated Wnt/PCP pathway on proliferation, myogenic differentiation, lipid accumulation, and expression of myogenic and adipogenic regulatory genes. These effects were evaluated in SCs isolated from the p. major muscle of 1-week faster-growing modern commercial (NC) line of turkeys as compared to SCs of a slower-growing historic Randombred Control Line 2 (RBC2) turkey line. Heat stress (43°C) increased phosphorylation of both ROCK and c-Jun with greater increases observed in the RBC2 line. Cold stress (33°C) had an inhibitory effect on both ROCK and c-Jun phosphorylation with the NC line showing greater reductions. Knockdown of the expression of Fzd7 decreased proliferation, differentiation, and expression of myogenic regulatory genes: myoblast determination factor-1 and myogenin in both lines. Both lipid accumulation and expression of adipogenic regulatory genes: peroxisome proliferator-activated receptor-γ, CCAAT/enhancer-binding protein-β, and neuropeptide-Y were suppressed with the Fzd7 knockdown. The RBC2 line was more dependent on the Fzd7-mediated Wnt/PCP pathway for proliferation, differentiation, and lipid accumulation compared to the NC line. Thus, thermal stress may affect poultry breast muscle growth potential and protein to fat ratio by altering function and fate of SCs through the Fzd7-mediated Wnt/PCP pathway in a growth-dependent manner.
Tumor Microbiome in Nasopharyngeal Carcinoma and Its Association With Prognosis

Introduction Previous studies have reported a close relationship between cancer and microbes, particularly gut and tumor microbiota; however, the presence of tumor microbiome in nasopharyngeal carcinoma (NPC) and its role in the prognosis of NPC remain unclear. Methods We collected 64 samples including tissues from 50 patients with NPC (NPC group) and 14 patients with chronic nasopharyngitis (control group) receiver operating characteristics and we applied 16S ribosome RNA gene sequencing of all samples to assess microbiome profiles and immunohistochemistry to detect tumor microbiome in NPC. Results Patients in the control group harbored higher species diversity than those in the NPC group; however, the beta diversity was more distinct in the NPC group. In total, three genera with statistically significant differences between the two groups were identified. The area under the receiver operating characteristics (ROC) curve (AUC) was calculated using the relative abundance of these three significant genera, and a value of 0.842 was achieved. Furthermore, Turicibacter was confirmed as a potentially independent prognostic factor for NPC patients, and the progression-free survival (PFS) was markedly prolonged in patients with a low relative abundance of Turicibacter compared to patients with a high relative abundance of this genus (cutoff: 0.0046, hazard ratio: 5.10, 95% confidence interval: 2.04–12.77, p = 0.004). Conclusions The present study provided strong evidence of a correlation between tumor microbiome and NPC; the tumor microbiome may be considered a biomarker for early NPC diagnosis. Turicibacter potentially served as a independently prognostic indicator for NPC patients.
Mg-, Zn-, and Fe-Based Alloys With Antibacterial Properties as Orthopedic Implant Materials

Implant-associated infection (IAI) is one of the major challenges in orthopedic surgery. The development of implants with inherent antibacterial properties is an effective strategy to resolve this issue. In recent years, biodegradable alloy materials have received considerable attention because of their superior comprehensive performance in the field of orthopedic implants. Studies on biodegradable alloy orthopedic implants with antibacterial properties have gradually increased. This review summarizes the recent advances in biodegradable magnesium- (Mg-), iron- (Fe-), and zinc- (Zn-) based alloys with antibacterial properties as orthopedic implant materials. The antibacterial mechanisms of these alloy materials are also outlined, thus providing more basis and insights on the design and application of biodegradable alloys with antibacterial properties as orthopedic implants.
Stronger Together: Examining the Interaction Effects of Workplace Dignity and Workplace Inclusion on Employees’ Job Performance

Despite growing interest in workplace dignity, there is a paucity of empirical research regarding whether and when it leads to higher job performance. To address these research gaps, this study examines the relationship between workplace dignity and job performance, identifying and examining the boundary condition role of workplace inclusion. Multi-source and time-lagged data were obtained from employee–supervisor dyads (n = 169) in non-governmental organizations in Pakistan to test the hypothesized model, employing techniques, such as confirmatory factor analysis, moderated multiple regression, post-hoc slope, and Johnson–Neyman analyses. As predicted, workplace dignity and workplace inclusion positively influenced employees’ job performance, while workplace inclusion moderated the dignity-performance relationship such that this relationship was more strongly positive when workplace inclusion was high. At the theoretical level, this study adds new insights to the job demands-resources (JD-R) model, which is used as theoretical lens in this study. Specifically, this study is the first to examine workplace dignity and its consequences from the perspective of the JD-R model, thus introducing a new theoretical perspective into the dignity literature. This study also provides useful advice for management practice, policymaking, and employees, and is germane to the United Nations’ Sustainable Development Goal 8.