Miracle-dz/UniFAR-FTUs huggingface dataset:
Prospective evaluation of 5 urinary biomarkers as predictors of acute kidney injury in nonazotemic, hospitalized dogs

Abstract Background Early recognition of acute kidney injury (AKI) is hindered by current definitions and use of traditional, insensitive markers. Hypothesis/Objectives Urinary (u) activity of γ‐glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP), and concentrations of heat‐shock protein 70 (HSP70) and interleukins (ILs) ‐6 and ‐18, are predictive biomarkers for AKI and survival. Animals Nonazotemic, hospitalized dogs (n = 118) and healthy controls (n = 20). Methods A prospective observational study. Nonazotemic dogs at risk of AKI were recruited and their urinary biomarker concentrations were measured at presentation. Serum creatinine (sCr) and symmetric dimethylarginine (sSDMA) were measured daily until discharge/death. Results The overall case fatality rate was 18.6%. Fifteen dogs (12.7%) developed AKI, which was associated with death (relative risk, 3.2; 95% confidence interval [CI], 1.57‐6.55). All 5 urinary biomarkers were significantly higher in hospitalized dogs compared to controls, with minimal overlap. uHSP70/uCr, uGGT/uCr, and uIL‐6/uCr at presentation were higher in dogs which later developed AKI. Areas under the receiver operator characteristic curve (AUROC) (95% CI) for the 3 biomarkers as predictors of AKI were 0.67 (0.51‐0.83), 0.68 (0.55‐0.81), and 0.78 (0.65‐0.91), respectively. When they were categorically classified as elevated/normal, each additional elevated biomarker increased the odds for AKI (OR, 2.83; 95% CI, 1.23‐6.52, P = .01). Agreement between sCr and sSDMA was poor (Cohen's kappa = .071). The AUROC of SDMA at presentation for AKI prediction was 0.73 (0.51‐0.95). Conclusions and Clinical Importance Kidney injury was common, irrespective of subsequent worsening of azotemia or death. The predictive value of individual urinary biomarkers was reduced by moderate sensitivities and specificities. SDMA showed moderate discriminatory utility for AKI prediction, and often displayed discordant results with sCr.
Bach1 derepression is neuroprotective in a mouse model of Parkinson’s disease

Significance The Keap1-Nrf2 signaling pathway is a promising therapeutic target for Parkinson’s disease (PD). Canonical Nrf2 activators targeting Keap1 thiols are known to be preventive but never effectively cure chronic neurodegeneration because of their electrophilic nature, resulting in nonspecific reactions with active cysteine residues in a variety of cellular proteins. We show that genetic and pharmacologic inhibition of the Nrf2 repressor Bach1 in a posttreatment regimen of experimental PD is neuroprotective by up-regulating Bach1-targeted pathways involving both Nrf2-dependent antioxidant response element (ARE) and non-ARE genes. Inhibition of Bach1 by a nonelectrophilic substituted benzimidazole is a promising therapeutic approach for PD. Parkinson's disease (PD) is a progressive neurodegenerative movement disorder characterized by the loss of nigrostriatal dopaminergic neurons. Mounting evidence suggests that Nrf2 is a promising target for neuroprotective interventions in PD. However, electrophilic chemical properties of the canonical Nrf2-based drugs cause irreversible alkylation of cysteine residues on cellular proteins resulting in side effects. Bach1 is a known transcriptional repressor of the Nrf2 pathway. We report that Bach1 levels are up-regulated in PD postmortem brains and preclinical models. Bach1 knockout (KO) mice were protected against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity and associated oxidative damage and neuroinflammation. Functional genomic analysis demonstrated that the neuroprotective effects in Bach1 KO mice was due to up-regulation of Bach1-targeted pathways that are associated with both Nrf2-dependent antioxidant response element (ARE) and Nrf2-independent non-ARE genes. Using a proprietary translational technology platform, a drug library screen identified a substituted benzimidazole as a Bach1 inhibitor that was validated as a nonelectrophile. Oral administration of the Bach1 inhibitor attenuated MPTP neurotoxicity in pre- and posttreatment paradigms. Bach1 inhibitor–induced neuroprotection was associated with the up-regulation of Bach1-targeted pathways in concurrence with the results from Bach1 KO mice. Our results suggest that genetic deletion as well as pharmacologic inhibition of Bach1 by a nonelectrophilic inhibitor is a promising therapeutic approach for PD.
Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy

Abstract Background The phase 3 VIALE-A trial (NCT02993523) reported that venetoclax-azacitidine significantly prolonged overall survival compared with placebo-azacitidine in patients with newly diagnosed acute myeloid leukemia ineligible for intensive chemotherapy. Herein, efficacy and safety of venetoclax-azacitidine are analyzed in the Japanese subgroup of VIALE-A patients. Methods Eligible Japanese patients were randomized 2:1 to venetoclax-azacitidine (N = 24) or placebo-azacitidine (N = 13). Primary endpoints for Japan were overall survival and complete response (CR) + CR with incomplete hematologic recovery (CRi). Venetoclax (target dose 400 mg) was given orally once daily. Azacitidine (75 mg/m2) was administered subcutaneously or intravenously on Days 1–7 of each 28-day cycle. Results Median follow-up was 16.3 months (range, 1.0–20.3). Median overall survival was not reached with venetoclax-azacitidine (hazard ratio 0.409 and 95% confidence interval: 0.151, 1.109); overall survival estimate was higher with venetoclax-azacitidine than placebo-azacitidine at 12 (67 and 46%) and 18 months (57 and 31%), respectively. CR and CRi rates were 67% with venetoclax-azacitidine and 15% with placebo-azacitidine. Most common any-grade adverse events were febrile neutropenia (79 and 39%), thrombocytopenia (54 and 77%), constipation (54 and 54%) and decreased appetite (54 and 38%) in the venetoclax-azacitidine and placebo-azacitidine arms, respectively. Only 1 patient in the venetoclax-azacitidine arm, and no patients in the placebo-azacitidine arm, had grade 4 febrile neutropenia that led to treatment discontinuation. Conclusions This Japanese subgroup analysis of VIALE-A demonstrates comparable safety and efficacy outcomes compared with the global study and supports venetoclax-azacitidine as first-line standard-of-care for Japanese treatment-naive patients with acute myeloid leukemia who are ineligible for intensive chemotherapy.
Lung function trajectory in progressive fibrosing interstitial lung disease

Background Proposed criteria for progressive fibrosing interstitial lung disease (PF-ILD) have been linked to increased mortality risk, but lung function trajectory after satisfying individual criteria remains unknown. Because survival is rarely employed as the primary end-point in therapeutic trials, identifying PF-ILD criteria that best predict subsequent change in forced vital capacity (FVC) could improve clinical trial design. Methods A retrospective, multicentre longitudinal cohort analysis was performed in consecutive patients with fibrotic connective tissue disease-associated ILD (CTD-ILD), chronic hypersensitivity pneumonitis and idiopathic interstitial pneumonia at three US centres (test cohort) and one UK centre (validation cohort). 1-year change in FVC after satisfying proposed PF-ILD criteria was estimated using joint modelling. Subgroup analyses were performed to determine whether results varied across key subgroups. Results 1227 patients were included, with CTD-ILD predominating. Six out of nine PF-ILD criteria were associated with differential 1-year change in FVC, with radiological progression of fibrosis, alone and in combination with other features, associated with the largest subsequent decline in FVC. Findings varied significantly by ILD subtype, with CTD-ILD demonstrating little change in FVC after satisfying most PF-ILD criteria, while other ILDs showed significantly larger changes. Findings did not vary after stratification by radiological pattern or exposure to immunosuppressant therapy. Near-term change in FVC after satisfying proposed PF-ILD criteria was heterogeneous depending on the criterion assessed and was strongly influenced by ILD subtype. Conclusions These findings may inform future clinical trial design and suggest ILD subtype should be taken into consideration when applying PF-ILD criteria. Lung function trajectory varies considerably following ILD diagnosis and after satisfying proposed PF-ILD criteria according to ILD diagnosis. These findings suggest diagnosis should be taken into consideration when designing ILD clinical trials. https://bit.ly/2ZF8C7V
Prediction of heterosis in the recent rapeseed (Brassica napus) polyploid by pairing parental nucleotide sequences

The utilization of heterosis is a successful strategy in increasing yield for many crops. However, it consumes tremendous manpower to test the combining ability of the parents in fields. Here, we applied the genomic-selection (GS) strategy and developed models that significantly increase the predictability of heterosis by introducing the concept of a regional parental genetic-similarity index (PGSI) and reducing dimension in the calculation matrix in a machine-learning approach. Overall, PGSI negatively affected grain yield and several other traits but positively influenced the thousand-seed weight of the hybrids. It was found that the C subgenome of rapeseed had a greater impact on heterosis than the A subgenome. We drew maps with overviews of quantitative-trait loci that were responsible for the heterosis (h-QTLs) of various agronomic traits. Identifications and annotations of genes underlying high impacting h-QTLs were provided. Using models that we elaborated, combining abilities between an Ogu-CMS-pool member and a potential restorer can be simulated in silico, sidestepping laborious work, such as testing crosses in fields. The achievements here provide a case of heterosis prediction in polyploid genomes with relatively large genome sizes.
Correlation of Fracture Resistance of Dental Implants and Bite Force in Dogs described in the literature: An In Vitro Study

Dental implants are not routinely used for rehabilitation in veterinary dentistry. For some veterinarians, further studies are necessary to be considered for clinical use in animals. The objective of the present in vitro study was to evaluate static fatigue of dental implants and to correlate that with the bite strength of dogs described in the literature. Sixty implants and abutments were used with the smallest diameter of each brand of implant utilized in the study. Three groups (n = 20) were created on the basis of the implant diameter, all with external hex connector: 3.30 mm (group 1), 4.0 mm (group 2) and 5.0 mm (group 3). All groups were subjected to quasi-static loading at 30° to the implant's long axis in a universal machine (model AME-5 kN). The mean fracture strength for group 1 was 964 ± 187 N, for group 2 was 1618 ± 149 N and for group 3 was 2595 ± 161 N. Significant differences between the groups with respect to resistance after the load applications were observed (P < .05). The diameter of implants affects the resistance to external forces during the application of non-axial strength (off-axis loading) and must be considered during the planning of rehabilitation to avoid problems.
An analysis of risk management in practice: the case of Ghana’s construction industry

Purpose – The purpose of this paper is to report the findings of research into the levels of awareness, usage and benefits of risk assessment and management practices (RAMP) within the construction industry in Ghana. Design/methodology/approach – The study was conducted through a structured questionnaire administered to 103 construction professionals practising with construction client (private and public), consultant and contractor organisations within the Ghanaian construction industry. The results were analysed to establish the current levels of awareness, usage and perceived benefits of risk management practices. Survey response data were subjected to descriptive statistics; subsequently, ANOVA and other non-parametric tests were used to examine the differences in the levels of agreement of the perceived benefits. Findings – This study illustrates that although the majority of the respondents are aware of RAMP, some professionals found the process not to be formal. Relative to the benefits, there was .
AZD3759 enhances radiation effects in non-small-cell lung cancer by a synergistic blockade of epidermal growth factor receptor and Janus kinase-1

ABSTRACT AZD3759 is a novel epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) on the basis of gefitinib and has been proven to enter the central nervous system. Although the promising antitumor effects of AZD3759 on non-small cell lung cancer (NSCLC) have been demonstrated in clinical trials, the regulatory effects of this inhibitor on the antitumor efficacy of radiation (RA) are unclear. The present study aimed to compare the effects of AZD3759 and osimertinib on RA efficacy in NSCLC and explore the potential mechanism of action of AZD3759. We found that the survival in RA-treated NSCLC cells was significantly decreased by treatment with 500 nM AZD3759 and osimertinib at the RA dosage of 8 Gy. The apoptotic rate, cell cycle arrest, and DNA damage in RA-treated NSCLC cells and brain metastasis in RA-treated xenograft nude mice were significantly enhanced by the co-administration of AZD3759 and osimertinib, respectively. In addition, AZD3759 showed a significantly stronger efficacy than osimertinib did. Mechanistically, the receptor tyrosine kinase signaling antibody array revealed that Janus kinase-1 (JAK1) was specifically inhibited by AZD3759, but not by osimertinib. The effects of AZD3759 on RA efficacy in PC-9 cells and in a brain metastasis animal model were significantly abolished by the overexpression of JAK1. Collectively, our results suggested that AZD3759 promoted RA antitumor effects in NSCLC by synergistic blockade of EGFR and JAK1.
Genome size estimation of Chinese cultured artemisia annua L.

Cite this article: Liu Z, Guo S, Xu J, Zhang Y, Dong L, et al. Genome size estimation of Chinese cultured artemisia annua L. J Plant Biol Crop Res. 2018; 1: 1002. Zhixiang Liu1; Shuai Guo1,2; Jiang Xu1*; Yujun Zhang1; Linlin Dong1; Shuiming Xiao1; Rui Bai3; Baosheng Liao1; He Su1,4; Ruiyang Cheng1; Shilin Chen1 1Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China 2College of Agriculture/College of Peony, Henan University of Science and Technology, Luoyang, Henan 471023, China 3College of Pharmacy and Chemistry, Dali University, Dali, Yunan 671000, China 4Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, and China Academy of Chinese Medical Sciences Guangdong Branch, China Academy of Chinese Medical Sciences, Guangzhou, 510006, China
Occurrence of SARS-CoV-2 infection among healthcare personnel: results from an early systematic review and meta-analysis

Background. SARS-CoV-2 infection has become a global public health concern globally. Even though Healthcare Workers (HCWs) are supposedly at increased risk for SARS-CoV-2 infection, to date no pooled evidence has been collected. Materials and Methods. We searched online electronic databases (PubMed, Embase, medRxiv.org for pre-prints) for all available contribution (up to May 20, 2019). Two Authors independently screened articles and extracted the data. The pooled prevalence of SARS-CoV-2 was analyzed using the random-effects model. The possible sources of heterogeneity were analyzed through subgroup analysis, and meta-regression. Results. The overall pooled prevalence of SARS-CoV-2 was 3.5% (95%CI 1.8–6.6) for studies based on molecular assays, 5.5% (95%CI 2.1–14.1) for studies based on serological assays, and 6.5% (95%CI 2.5–15.6) for point-of-care capillary blood tests. Among subgroups, serological tests identified higher risk for SARS-CoV-2 seropositivity in physicians than in nurses (OR 1.436, 95%CI 1.026 to 2.008). Regression analysis indicated the possible presence of publication bias only for molecular tests (t -3.3526, p-value 0.002648). Conclusions. The overall pooled prevalence of SARS-CoV-2 was lower than previously expected, but available studies were affected by significant heterogeneity, and the molecular studies by significant publication bias. Therefore, further high-quality research in the field is warranted. (www.actabiomedica.it)
Bacterial agents and their antibiotic susceptibility in neonatal sepsis in high dependency NICU of Tertiary Care Hospital

Background: The type of bacterial flora causing neonatal sepsis varies in different parts of world and the emerging of resistance to various antibiotics has been a challenge currently faced by microbiologists and neonatologist’s worldwide. The aim of this study was to isolate the bacteriological agent causing the neonatal sepsis and determination of their susceptibility to antibiotics. Methods: In this study, neonates suspected of sepsis who were admitted to Neonatal Intensive Care Unit (NICU) were assessed. Neonates with positive blood culture and with clinical signs of sepsis were enrolled in the study. The other parameters included: age, sex, birth weight, gestation, type of infection, type of isolated pathogen along with their antibiotic sensitivity and the outcome of disease. Results: 1440 neonates with suspected sepsis were included in study, out of 1440 patients, blood cultures were taken from all patients, 180cultures (12.5%) were reported as positive. in 32 cultures (17.7%) gram positive microbes were isolated while in 148 cultures (82.2%) gram negative microorganisms were detected.The mostcommon microorganisms isolated were; Klebsiella pneumonia (33.05%), Acintobacter Spp. (17.01%), Pseudomonas (13.26%), Escherishia-coli (8.75%),Coagulase negative staphylococci (CONS) (11.94%), MRSA (6.59%), Enterobacter (4.44%), Citrobacter (4.37%) and Enterococcus(2.36%). All of the klebsiella and enterobacter strains were resistant to ampicillin and gentamicin. Acintobacter Spp. , and Citrobacter, were multidrug resistant with their sensitivity to imipenem was 40 to 45 % while for tigicycline was near 90%. The sensitivity of K. pneumonia and enterobacter to imipenem was: 90 and 94%, respectively.61. 66% of our patients were preterm, early and late-onset sepsis was seen in 71 and 29% of patients respectively. Mortality rate was high 61.76% among preterm patients with sepsis while as overall mortality rate was 37.77%. Conclusion: In this study we found most common cause of bacterial sepsis was K. pneumoniae which was completely resistant to ampicillin and gentamicin. It therefore re-emphasis the need to change the empirical treatment of sepsis with ampicillin and gentamicin.
Psychosocial Factors Predict COVID-19 Vaccine Side Effects

aDepartment of Psychology, University of Toledo, Toledo, OH, USA; bSchool of Psychology, University of New South Wales, Sydney, NSW, Australia; cSchool of Psychology, University of Sydney, Sydney, NSW, Australia; dDepartment of Psychology, University of Sheffield, South Yorkshire, UK; eDepartment of Psychology and Behavioural Sciences, Aarhus University, Aarhus, Denmark; fDepartments of Pain Translational Symptoms Science, University of Maryland, Baltimore, MD, USA Received: August 24, 2021 Accepted: September 22, 2021 Published online: November 4, 2021
Value of Fecal Calprotectin Measurement During the Initial Period of Therapeutic Anti-Tubercular Trial

Background/Aims The diagnosis of intestinal tuberculosis (ITB) is often challenging. Therapeutic anti-tubercular trial (TATT) is sometimes used for the diagnosis of ITB. We aimed to evaluate the changing pattern of fecal calprotectin (FC) levels during TATT in patients with ITB. Methods A retrospective review was performed on the data of 39 patients who underwent TATT between September 2015 and November 2018 in five university hospitals in Daegu, South Korea. The analysis was performed for 33 patients with serial FC measurement reports. Results The mean age of the participants was 48.8 years. The final diagnosis of ITB was confirmed in 30 patients based on complete mucosal healing on follow-up colonoscopy performed after 2 months of TATT. Before starting TATT, the mean FC level of the ITB patients was 170.2 μg/g (range, 11.5-646.5). It dropped to 25.4 μg/g (range, 11.5-75.3) and then 23.3 μg/g (range, 11.5-172.2) after one and two months of TATT, respectively. The difference in mean FC before and one month after TATT was statistically significant (p<0.001), and FC levels decreased to below 100 μg/g in all patients after one month of TATT. Conclusions All ITB patients showed FC decline after only 1 month of TATT, and this finding correlated with complete mucosal healing in the follow-up colonoscopy after 2 months of TATT.
Romosozumab Enhances Vertebral Bone Structure in Women With Low Bone Density

Romosozumab monoclonal antibody treatment works by binding sclerostin and causing rapid stimulation of bone formation while decreasing bone resorption. The location and local magnitude of vertebral bone accrual by romosozumab and how it compares to teriparatide remains to be investigated. Here we analyzed the data from a study collecting lumbar computed tomography (CT) spine scans at enrollment and 12 months post‐treatment with romosozumab (210 mg sc monthly, n = 17), open‐label daily teriparatide (20 μg sc, n = 19), or placebo (sc monthly, n = 20). For each of the 56 women, cortical thickness (Ct.Th), endocortical thickness (Ec.Th), cortical bone mineral density (Ct.bone mineral density (BMD)), cancellous BMD (Cn.BMD), and cortical mass surface density (CMSD) were measured across the first lumbar vertebral surface. In addition, color maps of the changes in the lumbar vertebrae structure were statistically analyzed and then visualized on the bone surface. At 12 months, romosozumab improved all parameters significantly over placebo and resulted in a mean vertebral Ct.Th increase of 10.3% versus 4.3% for teriparatide, an Ec.Th increase of 137.6% versus 47.5% for teriparatide, a Ct.BMD increase of 2.1% versus a −0.1% decrease for teriparatide, and a CMSD increase of 12.4% versus 3.8% for teriparatide. For all these measurements, the differences between romosozumab and teriparatide were statistically significant (p < 0.05). There was no significant difference between the romosozumab‐associated Cn.BMD gains of 22.2% versus 18.1% for teriparatide, but both were significantly greater compared with the change in the placebo group (−4.6%, p < 0.05). Cortical maps showed the topographical locations of the increase in bone in fracture‐prone areas of the vertebral shell, walls, and endplates. This study confirms widespread vertebral bone accrual with romosozumab or teriparatide treatment and provides new insights into how the rapid prevention of vertebral fractures is achieved in women with osteoporosis using these anabolic agents. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Community participation and public awareness in disaster mitigation

Describes how the Society for National Integration through Rural Development in India involves the local communities when developing disaster mitigation measures. Shows how participation of the community in resource identification, capabilities, coping mechanisms and vulnerability assessment will be more effective in the planning of a sensible and practical system, more suitable for the needs of the community. Covers contingency planning, community preparedness, task forces (comprising active youths in the ratio of one youth for ten families) and response mechanisms.