Miracle-dz/UniFAR-FTUs huggingface dataset:
Vitamin D is associated with blood lead exposure through bone turnover in type 2 diabetes patients

Background Bone is thought to be the reservoir of the human lead burden, and vitamin D is associated with bone turnover. We aimed to explore whether exposure to lower 25-hydroxy vitamin D (25(OH)D) levels was associated with higher blood lead levels (BLLs) by increasing the bone turnover rate in individuals with type 2 diabetes. Methods A total of 4103 type 2 diabetic men and postmenopausal women in Shanghai, China, were enrolled in 2018. Their 25(OH)D, β-C-terminal telopeptide (β-CTX), N-MID osteocalcin and procollagen type 1 N-peptide (P1NP) levels were detected. Their BLLs were determined by atomic absorption spectrometry. Mediation analyses were performed to identify the possible role that bone turnover played in the underlying mechanisms. Results In both the men and postmenopausal women, all three bone turnover markers were inversely associated with 25(OH)D and positively associated with the BLL (all P < 0.01) after adjusting for age, current smoking habits, metabolic parameters, duration of diabetes, vitamin D intake, and use of anti-osteoporosis medication. In the mediation analyses, none of the direct associations between 25(OH)D and BLL was significant for the three bone turnover markers, but all three bone turnover markers were found to be significant mediators of the indirect associations between 25(OH)D and BLL. Conclusion The association between vitamin D and BLL was fully mediated by bone turnover markers in type 2 diabetic patients (mediation effect). This finding suggested that vitamin D may protect against blood lead exposure from the bone reservoir by decreasing bone turnover in individuals with type 2 diabetes.
Transgenic plants expressing a Clostridium difficile spore antigen as an approach to develop low‐cost oral vaccines

Gastrointestinal infections caused by Clostridium difficile lead to significant impact in terms of morbidity and mortality, causing from mild symptoms, such as a low‐grade fever, watery stools, and minor abdominal cramping as well as more severe symptoms such as bloody diarrhea, pseudomembrane colitis, and toxic megacolon. Vaccination is a viable approach to fight against C. difficile and several efforts in this direction are ongoing. Plants are promising vaccine biofactories offering low cost, enhanced safety, and allow for the formulation of oral vaccines. Herein, the CdeM protein, which is a spore antigen associated with immunoprotection against C. difficile, was selected to begin the development of plant‐based vaccine candidates. The vaccine antigen is based in a fusion protein (LTB‐CdeM), carrying the CdeM antigen, fused to the carboxi‐terminus of the B subunit of the Escherichia coli heat‐labile enterotoxin (LTB) as a mucosal immunogenic carrier. LTB‐CdeM was produced in plants using a synthetic optimized gene according codon usage and mRNA stability criteria. The obtained transformed tobacco lines produced the LTB‐CdeM antigen in the range of 52–90 μg/g dry weight leaf tissues. The antigenicity of the plant‐made LTB‐CdeM antigen was evidenced by GM1‐ELISA and immunogenicity assessment performed in test mice revealed that the LTB‐CdeM antigen is orally immunogenic inducing humoral responses against CdeM epitopes. This report constitutes the first step in the development of plant‐based vaccines against C. difficile infection.
Phospho-regulation and function of ULK1-ATG13 during the cell cycle

ABSTRACT Although it has been reported that some autophagy-related proteins could regulate the cell cycle, the function of ULK1-ATG13, the only protein kinase complex in macroautophagy/autophagy, remains unclear. We recently found that mitotic ULK1 and ATG13 are both substrates of the key cell cycle regulator CDK1-CCNB/cyclin B. CDK1-induced ULK1-ATG13 phosphorylation promotes mitotic autophagy and cell cycle progression. Moreover, ULK1 and ATG13 double-knockout significantly inhibits cell cycle progression and tumor cell proliferation in vitro and in vivo. These findings bridge the mutual regulation between autophagic and mitotic key kinases and provide a theoretical basis for autophagy- and cell division-related diseases based on combination therapy.
Multi-omic analysis of stroke recurrence in African Americans from the Vitamin Intervention for Stroke Prevention (VISP) clinical trial

African Americans endure a nearly two-fold greater risk of suffering a stroke and are 2–3 times more likely to die from stroke compared to those of European ancestry. African Americans also have a greater risk of recurrent stroke and vascular events, which are deadlier and more disabling than incident stroke. Stroke is a multifactorial disease with both heritable and environmental risk factors. We conducted an integrative, multi-omic study on 922 plasma metabolites, 473,864 DNA methylation loci, and 556 variants from 50 African American participants of the Vitamin Intervention for Stroke Prevention clinical trial to help elucidate biomarkers contributing to recurrent stroke rates in this high risk population. Sixteen metabolites, including cotinine, N-delta-acetylornithine, and sphingomyelin (d17:1/24:1) were identified in t-tests of recurrent stroke outcome or baseline smoking status. Serum tricosanoyl sphingomyelin (d18:1/23:0) levels were significantly associated with recurrent stroke after adjusting for covariates in Cox Proportional Hazards models. Weighted Gene Co-expression Network Analysis identified moderate correlations between sphingolipid markers and clinical traits including days to recurrent stroke. Integrative analyses between genetic variants in sphingolipid pathway genes identified 29 nominal associations with metabolite levels in a one-way analysis of variance, while epigenomic analyses identified xenobiotics, predominately smoking-associated metabolites and pharmaceutical drugs, associated with methylation profiles. Taken together, our results suggest that metabolites, specifically those associated with sphingolipid metabolism, are potential plasma biomarkers for stroke recurrence in African Americans. Furthermore, genetic variation and DNA methylation may play a role in the regulation of these metabolites.
Review of multi-species biofilm formation from foodborne pathogens: multi-species biofilms and removal methodology

Abstract Multi-species biofilms are ubiquitous worldwide and are a concern in the food industry. Multi-species biofilms have a higher resistance to antimicrobial therapies than mono-species biofilms. In addition, multi-species biofilms can cause severe foodborne diseases. To remove multi-species biofilms, controlling the formation process of extracellular polymeric substances (EPS) and quorum sensing (QS) effects is essential. EPS disruption, inhibition of QS, and disinfection have been utilized to remove multi-species biofilms. This review presents information on the formation and novel removal methods for multi-species biofilms.
The pronounced lung lesions developing in LATY136F knock-in mice mimic human IgG4-related lung disease

Rationale Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a novel clinical disease entity characterized by an elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4-positive plasma cells. Pathological changes are most frequently seen in the pancreas, lacrimal glands, and salivary glands, but pathological changes in the lung also exist. Linker for activation of T cell (LAT)Y136F knock-in mice show Th2-dominant immunoreactions with elevated serum IgG1 levels, corresponding to human IgG4. We have reported that LATY136F knock-in mice display several characteristic features of IgG4-RD and concluded that they constitute an appropriate model of human IgG4-RD in salivary glands, pancreas, and kidney lesions. Objectives The aim of this study is to evaluate whether lung lesions in LATY136F knock-in mice can be a model of IgG4-related lung disease. Methods Lung tissue samples from LATY136F knock-in mice (LAT) and wild-type mice (WT) were immunostained for IgG1 and obtained for pathological evaluation, and cell fractions and cytokine levels in broncho-alveolar lavage fluid (BALF) were analyzed. Results In the LAT group, IgG1-positive inflammatory cells increased starting at 4 weeks of age and peaked at 10 weeks of age. The total cell count and percentage of lymphocytes increased significantly in BALF in the LAT group compared to the WT group. In BALF, Th2-dominant cytokines and transforming growth factor-β were also increased. In the LAT group, marked inflammation around broncho-vascular bundles peaked at 10 weeks of age. After 10 weeks, fibrosis around broncho-vascular bundles and bronchiectasis were observed in LATY136F knock-in mice but not WT mice. Conclusions LATY136F knock-in mice constitute an appropriate model of lung lesions in IgG4-RD.
Middle Meningeal Artery Embolization Using Combined Particle Embolization and n-BCA with the Dextrose 5% in Water Push Technique for Chronic Subdural Hematomas: A Prospective Safety and Feasibility Study

BACKGROUND AND PURPOSE: Embolization of the middle meningeal artery for treatment of refractory or recurrent chronic subdural hematomas has gained momentum during the past few years. Little has been reported on the use of the n-BCA liquid embolic system for middle meningeal artery embolization. We present the technical feasibility of using diluted n-BCA for middle meningeal artery embolization. MATERIALS AND METHODS: We sought to examine the safety and technical feasibility of the diluted n-BCA liquid embolic system for middle meningeal artery embolization. Patients with chronic refractory or recurrent subdural hematomas were prospectively enrolled from September 2019 to June 2020. The primary outcome was the safety and technical feasibility of the use of diluted n-BCA for embolization of the middle meningeal artery. The secondary end point was the efficacy in reducing hematoma volume. RESULTS: A total of 16 patients were prospectively enrolled. Concomitant burr-hole craniotomies were performed in 12 of the 16 patients. Two patients required an operation following middle meningeal artery embolization for persistent symptoms. The primary end point was met in 100% of cases in which there were no intra- or postprocedural complications. Distal penetration of the middle meningeal artery branches was achieved in all the enrolled cases. A 7-day post–middle meningeal artery embolization follow-up head CT demonstrated improvement (>50% reduction in subdural hematoma volume) in 9/15 (60%) patients, with 6/15 (40%) showing an unchanged or stable subdural hematoma. At day 21, available CT scans demonstrated substantial further improvement (>75% reduction in subdural hematoma volume). CONCLUSIONS: Embolization of the middle meningeal artery using diluted n-BCA and ethiodized oil (1:6) is safe and feasible from a technical standpoint. The use of a dextrose 5% bolus improves distal penetration of the glue.
Semiconductor Growth and Junction Formation within Nano-Porous Oxides

We report a systematic study of the chemical properties of porous silicon as a moderate reducing agent and a nano-structure template for the reductive formation of nano-metal cluster aggregates. This study investigates the consequences of the interaction of silver ions in aqueous solution with porous silicon. The nature of the redox reaction, especially the role of surface hydrogen and silicon atoms, is established through the study of the morphology, structure, and electronic and optical properties of Ag on porous silicon. The specimens were characterized with SEM and X-ray absorption fine structure (XAFS) spectroscopy using synchrotron radiation
Connected to the spirit of the frog: An Internet-based survey on Kambô, the secretion of the Amazonian Giant Maki Frog (Phyllomedusa bicolor): Motivations for use, settings and subjective experiences

Background/aim: Kambô is a name for the secretion of the Giant Maki Frog (Phyllomedusa bicolor), which has been used by indigenous cultures from the Amazonas basin and has recently become popular in alternative healing circles in Western countries, with a certain overlap with psychedelic self-exploration. Methods: We carried out an online-based survey in English (54.92%) and German investigating motivations for using Kambô, settings in which rituals take place, and subjective experiences during and after the application. Results: Participants (n = 386, mean age: 38.08 years, (standard deviation = 9.95)) were well-educated individuals with an increased lifetime prevalence of the use of ayahuasca (67.88%). A plethora of motivations for using Kambô was reported, including general healing, detoxification and spiritual growth. Acute effects included severe physical reactions and mild psychoactive effects, most surprisingly, the feeling of being connected to the frog’s spirit (41.97%), whereas predominantly positive persisting psychological effects were reported. Few participants reported long-lasting physical (2.85%) or mental (1.81%) health problems which they attributed to Kambô. Of the participants, 87.31% reported an increase in personal well-being or life satisfaction, and 64.26% considered Kambô to have been at least of ‘very much’ spiritual significance for their lives. Conclusions: The majority of users claimed beneficial effects including more health-orientated behaviors, whereas only very few participants complained about new health problems which they ascribed to Kambô. In retrospect, Kambô was given a high personal and spiritual significance by many participants. Additional research is needed to determine in how far reported effects are modulated by setting and subjective expectations.
Trajectory of Cognitive Decline After Sepsis

Supplemental Digital Content is available in the text. OBJECTIVES: Cognitive impairment is an important consequence of sepsis. We sought to determine long-term trajectories of cognitive function after sepsis. DESIGN: Prospective study of the Reasons for Geographic and Racial Differences in Stroke cohort. SETTING: United States. PATIENTS: Twenty-one thousand eight-hundred twenty-three participants greater than or equal to 45 years, mean (sd) age 64.3 (9.2) years at first cognitive assessment, 30.9% men, and 27.1% Black. MEASUREMENTS AND MAIN RESULTS: The main exposure was time-dependent sepsis hospitalization. The primary outcome was global cognitive function (Six-Item Screener range, 0–6). Secondary outcomes were incident cognitive impairment (Six-Item Screener score ≤ 4 [impaired] vs ≥5 [unimpaired]), new learning (Consortium to Establish a Registry for Alzheimer Disease Word List Learning range, 0–30), verbal memory (word list delayed recall range, 0–10), and executive function/semantic fluency (animal fluency test range, ≥ 30). Over a median follow-up of 10 years (interquartile range, 6–12 yr), 840 (3.8%) experienced sepsis (incidence 282 per 1,000 person-years). Sepsis was associated with faster long-term declines in Six-Item Screener (–0.02 points per year faster [95% CI, –0.01 to –0.03]; p < 0.001) and faster long-term rates of incident cognitive impairment (odds ratio 1.08 per year [95% CI, 1.02–1.15]; p = 0.008) compared with presepsis slopes. Although cognitive function acutely changed after sepsis (0.05 points [95% CI, 0.01–0.09]; p = 0.01), the odds of acute cognitive impairment (Six-Item Screener ≤ 4) immediately after sepsis was not significant (odds ratio, 0.81 [95% CI, 0.63–1.06]; p = 0.12). Sepsis hospitalization was not associated with acute changes or faster declines in word list learning, word list delayed recall, or animal fluency test. CONCLUSIONS: Sepsis is associated with accelerated long-term decline in global cognitive function.
Cardiometabolic risk factors for COVID-19 susceptibility and severity: A Mendelian randomization analysis

Importance: Early epidemiological studies report associations of diverse cardiometabolic conditions especially body mass index (BMI), with COVID-19 susceptibility and severity, but causality has not been established. Identifying causal risk factors is critical to inform preventive strategies aimed at modifying disease risk. Objective: We sought to evaluate the causal associations of cardiometabolic conditions with COVID-19 susceptibility and severity. Design: Two-sample Mendelian Randomization (MR) Study. Setting: Population-based cohorts that contributed to the genome-wide association study (GWAS) meta-analysis by the COVID-19 Host Genetics Initiative. Participants: Patients hospitalized with COVID-19 diagnosed by RNA PCR, serologic testing, or clinician diagnosis. Population controls defined as anyone who was not a case in the cohorts. Exposures: Selected genetic variants associated with 17 cardiometabolic diseases, including diabetes, coronary artery disease, stroke, chronic kidney disease, and BMI, at p<5 x 10-8 from published largescale GWAS. Main outcomes: We performed an inverse-variance weighted averages of variant-specific causal estimates for susceptibility, defined as people who tested positive for COVID-19 vs. population controls, and severity, defined as patients hospitalized with COVID-19 vs. population controls, and repeated the analysis for BMI using effect estimates from UKBB. To estimate direct and indirect causal effects of BMI through obesity-related cardiometabolic diseases, we performed pairwise multivariable MR. We used p<0.05/17 exposure/2 outcomes=0.0015 to declare statistical significance. Results: Genetically increased BMI was causally associated with testing positive for COVID-19 [6,696 cases / 1,073,072 controls; p=6.7 x 10-4, odds ratio and 95% confidence interval 1.08 (1.03, 1.13) per kg/m2] and a higher risk of COVID-19 hospitalization [3,199 cases/897,488 controls; p=8.7 x 10-4, 1.12 (1.04, 1.21) per kg/m2]. In the multivariable MR, the direct effect of BMI was abolished upon conditioning on the effect on type 2 diabetes but persisted when conditioning on the effects on coronary artery disease, stroke, chronic kidney disease, and c-reactive protein. No other cardiometabolic exposures tested were associated with a higher risk of poorer COVID-19 outcomes. Conclusions and Relevance: Genetic evidence supports BMI as a causal risk factor for COVID-19 susceptibility and severity. This relationship may be mediated via type 2 diabetes. Obesity may have amplified the disease burden of the COVID-19 pandemic either single-handedly or through its metabolic consequences.
DLIN: Deep Ladder Imputation Network

Many efforts have been dedicated to addressing data loss in various domains. While task-specific solutions may eliminate the respective issue in certain applications, finding a generic method for missing data estimation is rather complex. In this regard, this article proposes a novel missing data imputation algorithm, which has supreme generalization ability for a vast variety of applications. Making use of both complete and incomplete parts of data, the proposed algorithm reduces the effect of missing ratio, which makes it suitable for situations with very high missing ratios. In addition, this feature enables model construction on incomplete training sets, which is rarely addressed in the literature. Moreover, the nonparametric nature of this new algorithm brings about supreme flexibility against all variations of missing values and data distribution. We incorporate the advantages of denoising autoencoders and ladder architecture into a novel formulation based on deep neural networks. To evaluate the proposed algorithm, a comparative study is performed using a number of reputable imputation techniques. In this process, real-world benchmark datasets from different domains are selected. On top of that, a real cyber-physical system is also evaluated to study the generalization ability of the proposed algorithm for distinct applications. To do so, we conduct studies based on three missing data mechanisms, namely: 1) missing completely at random; 2) missing at random; and 3) missing not at random. The attained results indicate the superiority of the proposed method in these experiments.
Preoperative paraspinous muscle sarcopenia and physical performance as prognostic indicators in non‐small‐cell lung cancer

Despite the associations of both preoperative sarcopenia and physical performance with post‐operative mortality in non‐small‐cell lung cancer (NSCLC), there have been no comprehensive studies of the impact of physical status on prognosis. This study was performed to investigate the prognostic significance of preoperative sarcopenia and physical performance in NSCLC.
Synthesis of benzimidazole based hydrazones as non‐sugar based α‐glucosidase inhibitors: Structure activity relation and molecular docking

In search for α‐glucosidase inhibitors used in the treatment of diabetes mellitus, a series of unique benzimidazole based hydrazones derivatives were synthesized (5a‐5p), which were then investigated for their in vitro α‐glucosidase inhibitory potential. The compounds of interest were characterized by modern spectroscopic approaches including CHN, 1HNM R, 13CN MR and FTIR. The structure of compound 5n was distinctively authenticated through single crystal X‐ray study. All compounds depicted potent enzyme inhibitory potential with IC50 values in the range of 2.25 ± 0.01 to 81.16 ± 0.12 μM except 5n that showed IC50 value of 182.75 ± 0.13 μM. A limited structure–activity correlation demonstrated that substitutions of isatin, aldehydes and ketone in hydrazones moiety had remarkable contribution in the overall activity and that was further supported by molecular docking studies carried out in elucidating the mechanism of binding interaction of these compounds in the catalytic site of α‐glucosidase.
Modelling the factors affecting the probability for local rabies elimination by strategic control

Dog rabies has been recognized from ancient times and remains widespread across the developing world with an estimated 59,000 people dying annually from the disease. In 2011 a tri-partite alliance consisting of the OIE, the WHO and the FAO committed to globally eliminating dog-mediated human rabies by 2030. Regardless of global support, the responsibility remains with local program managers to implement successful elimination programs. It is well known that vaccination programs have a high probability of successful elimination if they achieve a population-coverage of 70%. It is often quoted that reducing population turnover (typically through sterilizations) raises the probability for local elimination by maintaining herd immunity for longer. Besides this, other factors that affect rabies elimination are rarely mentioned. This paper investigates the probability for local elimination as it relates to immunity, fecundity, dog population size, infectivity (bite rates), in-migration of immune-naïve dogs, and the initial incidence. To achieve this, an individual-based, stochastic, transmission model was manipulated to create a dataset covering combinations of factors that may affect elimination. The results thereof were analysed using a logistic regression model with elimination as the dependent variable. Our results suggest that smaller dog populations, lower infectivity and lower incidence (such as when epidemics start with single introductions) strongly increased the probability for elimination at wide ranges of vaccination levels. Lower fecundity and lower in-migration had weak effects. We discuss the importance of these findings in terms of their impact and their practical application in the design of dog-mediated rabies control programs.