Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of ancestry-specific polygenic risk score and diet composition in type 2 diabetes

Background Carbohydrate and protein dietary proportions have been debated as to whether higher or lower levels are optimal for diabetes metabolic control. Objective The objective of this study was to investigate the associations, interactions, and mediational relationships between a polygenic risk score (PRS), carbohydrate and protein intake, and physical activity level on type 2 diabetes (T2DM) by genetic ancestry, in European Americans and African Americans. A secondary objective examined the biological pathways associated with the PRS-linked genes and their relationships to dietary intake. Methods We performed a cross-sectional study in 9,393 participants: 83.3% European Americans and 16.7% African Americans from 7-NHLBI Care studies obtained from the database of Genotypes and Phenotypes. The main outcome was T2DM. Carbohydrate and protein intake derived from food frequency questionnaires were calculated as percent calories. Data were analyzed using multivariable generalized estimation equation models to derive odds ratios (OR) and 95% confidence intervals (CI). Ancestry-specific PRSs were constructed using joint-effects Summary Best Linear Unbiased Estimation in the train dataset and replicated in the test dataset. Mediation analysis was performed using VanderWeele’s method. Results The PRS in the highest tertile was associated with higher risk of T2DM in European Americans (OR = 1.25;CI = 1.03–1.51) and African Americans (OR = 1.54;1.14–2.09). High carbohydrate and low protein intake had lower risks of T2DM when combined with the PRS after adjusting for covariates. In African Americans, high physical activity combined with the high PRS and high protein diet was associated with a 28% lower incidence of T2DM when compared to low physical activity. In mediational models in African Americans, the PRS-T2DM association was mediated by protein intake in the highest tertile by 55%. The top PRS tertile had the highest magnitude of risks with metabolic factors that were significantly associated with T2DM, especially in European Americans. We found metabolic pathways associated with the PRS-linked genes that were related to insulin/IGF and ketogenesis/ketolysis that can be activated by moderate physical activity and intermittent fasting for better T2DM control. Conclusions Clinicians may want to consider diets with a higher portion of carbohydrates than protein, especially when the burden of high-risk alleles is great in patients with T2DM. In addition, clinicians and other medical professionals may want to emphasize the addition of physical activity as part of treatment regimen especially for African Americans. Given the metabolic pathways we identified, moderate physical activity and intermittent fasting should be explored. Researchers may want to consider longitudinal or randomized clinical trials to determine the predictive ability of different dietary patterns to inhibit T2DM in the presence of obesity and an elevated PRS.
Cyclic di-AMP, a multifaceted regulator of central metabolism and osmolyte homeostasis in Listeria monocytogenes

Abstract Cyclic di-AMP is an emerging second messenger that is synthesized by many archaea and bacteria, including the Gram-positive pathogenic bacterium Listeria monocytogenes. Listeria monocytogenes played a crucial role in elucidating the essential function of c-di-AMP, thereby becoming a model system for studying c-di-AMP metabolism and the influence of the nucleotide on cell physiology. c-di-AMP is synthesized by a diadenylate cyclase and degraded by two phosphodiesterases. To date, eight c-di-AMP receptor proteins have been identified in L. monocytogenes, including one that indirectly controls the uptake of osmotically active peptides and thus the cellular turgor. The functions of two c-di-AMP-receptor proteins still need to be elucidated. Here, we provide an overview of c-di-AMP signalling in L. monocytogenes and highlight the main differences compared to the other established model systems in which c-di-AMP metabolism is investigated. Moreover, we discuss the most important questions that need to be answered to fully understand the role of c-di-AMP in osmoregulation and in the control of central metabolism.
Modeling the significance of dynamic capability on the performance of microfinance institutions

According to strategic management theory, dynamic capability plays a significant role in enhancing organizational performance. Using a cross-sectional research design, the current study quantitatively assesses the mediating effect of dynamic capability on the relationships of total quality management, customer intellectual capital, and human resource management practice with the performance of microfinance institutions. An online survey involving 120 members of Induk Koperasi Kredit, a credit union association in West Kalimantan, Indonesia, is conducted. All the data are subjected to variance-based partial least squares structural equation modeling (PLS-SEM) analysis. The obtained results demonstrate the significant and positive influence of total quality management and human resource management practice on dynamic capability. Furthermore, dynamic capability is found to mediate the relationship between total quality management and human resource management practice on the performance of microfinance institutions. However, this study is unable to conclude that total quality management and human resource management practice have any significant impact on the performance of microfinance institutions. Nonetheless, this study demonstrates the crucial need for microfinance institutions to enhance their management activities via dynamic capability to enhance performance. This is one of the earliest studies conducted during the COVID-19 pandemic to examine the capabilities and performance of microfinance institutions in Indonesia. Notably, the performance of microfinance institutions can be further sustained by improving customers’ intellectual and dynamic capabilities.
Correlations between three ELISA protocols measurements of RTS,S/AS01-induced anti-CSP IgG antibodies

Background RTS,S/AS01 induced anti-circumsporozoite protein (CSP) IgG antibodies are associated with the vaccine efficacy. There is currently no international standardisation of the assays used in the measurement of anti-CSP IgG antibody concentrations for use in evaluations of the vaccine’s immunogenicity and/or efficacy. Here, we compared the levels of RTS,S/AS01 induced anti-CSP IgG antibodies measured using three different enzyme-Linked ImmunoSorbent Assays (ELISA). Methods 196 plasma samples were randomly selected from the 447 samples collected during the RTS,S/AS01 phase IIb trial in 2007 from Kenyan children aged between 5–17 months. The vaccine-induced anti-CSP IgG antibodies were then measured using two independently developed ELISA protocols (‘Kilifi-RTS,S’ and ‘Oxford-R21’) and compared to the results from the reference ‘Ghent-RTS,S’ protocol for the same participants. For each pair of protocols, a deming regression model was fitted. Linear equations were then derived to aid in conversions into equivalent ELISA units. The agreement was assessed using Bland and Altman method. Findings The anti-CSP IgG antibodies measured from the three ELISA protocols were in agreement, and were positively and linearly correlated; ‘Oxford’ and ‘Kilifi’ r = 0.93 (95% CI 0.91–0.95), ‘Oxford’ and ‘Ghent’ r = 0.94 (95% CI: 0.92–0.96), and ‘Kilifi’ and ‘Ghent’ r = 0.97 (95% CI: 0.96–0.98), p<0.0001 for all correlations. Conclusions With the linearity, agreement and correlations established between the assays, conversion equations can be applied to convert results into equivalent units, enabling comparisons of immunogenicities across different vaccines of the same CSP antigens. This study highlights the need for the international harmonisation of anti-CSP antibody measurements.
Protein energy wasting in pre-dialysis chronic kidney disease patients in Benin City, Nigeria: A cross-sectional study

Introduction Protein energy wasting (PEW) is common among chronic kidney disease (CKD) patients, especially those with advanced stage. It worsens frailty, sarcopenia and debility in CKD patients. Despite the importance of PEW, it is not routinely assessed during management of CKD patients in Nigeria. The prevalence of PEW and its associated factors were determined in pre-dialysis CKD patients. Methods This was a cross-sectional study that involved 250 pre-dialysis CKD patients and 125 age- and sex- matched healthy controls. Body mass index (BMI), subjective global assessment (SGA) scores and serum albumin levels were used in PEW assessment. The factors associated with PEW were identified. P-value of < 0.05 was taken as significant. Results The mean age of CKD and control group were 52.3±16.0 years and 50.5±16.0 years, respectively. The prevalence of low BMI, hypoalbuminaemia and malnutrition defined by SGA in pre-dialysis CKD patients were 42.4%, 62.0% and 74.8%, respectively. The overall prevalence of PEW among the pre-dialysis CKD patients was 33.3%. On multiple logistic regression, the factors associated with PEW in CKD were being middle aged (adjusted odds ratio: 12.50; confidence interval: 3.42–45.00; p <0.001), depression (adjusted odds ratio: 2.34; confidence interval: 1.02–5.40; p = 0.046) and CKD stage 5 (adjusted odds ratio: 12.83; confidence interval: 3.53–46.60; p <0.001). Conclusion PEW is common in pre-dialysis CKD patients and it was associated with middle age, depression and advanced CKD. Early intervention aimed at addressing depression in early stages of CKD may prevent PEW and improve overall outcome in CKD patients.
Preparation and Characterization of Crayfish (Astacus leptodactylus) Chitosan with Different Deacetylation Degrees

Background: In this study, chitosan with various deacetylation degrees was extracted from crayfish (Astacus leptodactylus) shells with the purpose of examining the effect of deacetylation on the characterization of chitosan. Objectives: Recycling of wastes has become an important issue with the advancement of shellfish processing technology. Therefore, this study examined the most important and conventional characterization parameters of chitosan extracted from crayfish shells and investigated whether crayfish chitosan can be an alternative to commercial products. Material and Methods: In order to determine the characterization of the chitosan; degree of deacetylation, yield, molecular weight, apparent viscosity, water binding capacity, fat binding capacity, moisture content, ash content, color properties, Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and X-ray diffraction analyses (XRD) were applied. Results: The low (LDD) and high (HDD) deacetylated crayfish chitosan characterization results in terms of yield, molecular weight, apparent viscosity, water binding capacity, fat binding capacity, moisture content, ash content were 17.50%, 424.03-334.66 kDa, 16.82-9.63 cP, 481.29-428.04%, 419.30-355.75%, 3.32-1.03%, 0.98-1.01%, respectively. As detected by two different methods, potentiometric titration and elemental analysis, the deacetylation degrees of low and high crayfish chitosan were found close to each other, which were 76.98-94.98% and 73.79-92.06%, respectively. As the deacetylation period extended, acetyl groups were removed, and the degree of the deacetylation of crayfish chitosan increased while the apparent viscosity, molecular weight, water and fat binding capacity decreased. Conclusions: The findings of the present study are important to obtain the chitosan having various physicochemical characteristics from unevaluated crayfish wastes and to use it in many different sectors, especially biotechnology, medicine, pharmaceutical, food, and agriculture.
Prospective, multicenter study of antimicrobial-coated, noncrosslinked, acellular porcine dermal matrix (XenMatrix™ AB Surgical Graft) for hernia repair in all centers for disease control and prevention wound classes: 24-month follow-up cohort

Background: Prospective, multicenter, single-arm study of antimicrobial-coated, noncrosslinked, acellular porcine dermal matrix (AC-PDM) in a cohort involving all centers for disease control and prevention wound classes in ventral/incisional midline hernia repair (VIHR). Materials and methods: Seventy-five patients (mean age 58.6±12.7 years; BMI 31.3±4.9 kg/m2) underwent ventral/incisional midline hernia repair with AC-PDM. Surgical site occurrence (SSO) was assessed in the first 45 days post-implantation. Length of stay, return to work, hernia recurrence, reoperation, quality of life, and SSO were assessed at 1, 3, 6, 12, 18, and 24 months. Results: 14.7% of patients experienced SSO requiring intervention within 45 days post-implantation, and 20.0% thereafter (>45 d post-implantation). Recurrence (5.8%), definitely device-related adverse events (4.0%), and reoperation (10.7%) were low at 24 months; all quality-of-life indicators were significantly improved compared to baseline. Conclusion: AC-PDM exhibited favourable results, including infrequent hernia recurrence and definitely device-related adverse events, with reoperation and SSO comparable to other studies, and significantly improved quality of life.
Dissecting the relative contribution of ECA3 and group 8/9 cation diffusion facilitators to manganese homeostasis in Arabidopsis thaliana

Abstract Manganese (Mn) is an essential micronutrient for plant growth but becomes toxic when present in excess. A number of Arabidopsis proteins are involved in Mn transport including ECA3, MTPs, and NRAMPs; however, their relative contributions to Mn homeostasis remain to be demonstrated. A major focus here was to clarify the importance of ECA3 in responding to Mn deficiency and toxicity using a range of mutants. We show that ECA3 localizes to the trans‐Golgi and plays a major role in response to Mn deficiency with severe effects seen in eca3 nramp1 nramp2 under low Mn supply. ECA3 plays a minor role in Mn‐toxicity tolerance, but only when the cis‐Golgi‐localized MTP11 is non‐functional. We also use mutants and overexpressors to determine the relative contributions of MTP members to Mn homeostasis. The trans‐Golgi‐localized MTP10 plays a role in Mn‐toxicity tolerance, but this is only revealed in mutants when MTP8 and MTP11 are non‐functional and when overexpressed in mtp11 mutants. MTP8 and MTP10 confer greater Mn‐toxicity resistance to the pmr1 yeast mutant than MTP11, and an important role for the first aspartate in the fifth transmembrane domain DxxxD motif is demonstrated. Overall, new insight into the relative influence of key transporters in Mn homeostasis is provided.
Optimal Product Design by Sequential Experiments in High Dimensions

The identification of the optimal design of products and packaging is challenged when attributes and their levels interact. Firms recognize this by testing prototypes prior to launch, where the effects of interactions are revealed in the head-to-head comparison of a small number of finalists. A difficulty in conducting analysis for design is dealing with the high dimensionality of the design space. We propose an experimental criteria for sequentially searching for the most preferred design concept, and incorporate a stochastic search variable selection method to selectively estimate relevant interactions among the attributes. A validation experiment confirms that our proposed method leads to improved design concepts in a high-dimensional space compared to alternative methods.
A mathematical model for control of vector borne diseasesthrough media campaigns

Vector borne diseases spread rapidly in the population. Hence their control intervention must work quickly and target large area as well. A rational approach to combat these diseases is mobilizing people and making them aware through media campaigns. In the present paper, a non-linear mathematical model is proposed to assess the impact of creating awareness by the media on the spread of vector borne diseases. It is assumed that as a response to awareness, people will not only try to protect themselves but also take some potential steps to inhibit growth of vectors in the environment. The model is analyzed using stability theory of differential equations and numerical simulation. The equilibria and invasion threshold for infection i.e., basic reproduction number, has been obtained. It is found that the presence of awareness in the population makes the disease invasion difficult. Also, continuous efforts by the media along with the swift dissemination of awareness can completely eradicate the disease from the system.
The therapygenetics of anxiety disorders

Treatment of anxiety disorders primarily includes pharmacological treatment and psychotherapy, yet a substantial portion of patients do not experience sufficient clinical response. Given the significant impact of anxiety disorders on well-being and quality of life, it is pertinent to strive to ensure available treatments are of paramount efficacy. This review aimed to identify genetic variants and genes that may moderate the outcome of psychotherapy in patients with anxiety disorders, termed ‘therapygenetics. ’ A comprehensive search of the current literature following relevant guidelines was conducted. Eighteen records were included in the review. Seven studies reported significant associations between genetic variants and response to psychotherapy. The most investigated polymorphisms were the serotonin transporter-linked polymorphic region (5-HTTLPR), nerve growth factor rs6330, catechol-O-methyltransferase Val158Met, and brain-derived neurotrophic factor Val166Met. However, current findings are inconsistent and thus do not support the use of genetic variants for the prediction of psychotherapy response in anxiety disorders.
Biologics for severe asthma—Which, when and why?

Asthma is a common chronic inflammatory condition of the airways that affects about 350 million people globally. In 5%–10% of individuals, it is severe, with considerable morbidity and high health care utilization. The goal of asthma management is disease control by reducing symptoms and exacerbations and reducing corticosteroid‐related morbidity. The era of biologics has revolutionized the management of severe asthma. Biologics have changed our expectations for severe asthma, especially in those people with type‐2 mediated immunity. We can now explore the potential for changing disease trajectory and inducing remission. However, biologics are not a panacea for all severe asthma sufferers and despite their success there remains substantial unmet clinical need. We review the pathogenesis of asthma, phenotyping the heterogeneity of asthma, currently licensed and future biologic agents, how to choose the initial biologic, assessing the response, remission and switching of biologic therapies.
The Inactivated ISKNV-I Vaccine Confers Highly Effective Cross-Protection against Epidemic RSIV-I and RSIV-II from Cultured Spotted Sea Bass Lateolabrax maculatus

Red seabream iridovirus (RSIV) infects a wide mariculture bony fish and has resulted in significant annual economic loss worldwide. Previous studies showed that the phenotypic diversity of infectious RSIV isolates would lead to different virulence characteristics, viral antigenicity, and vaccine efficacy as well as host range. ABSTRACT The genus Megalocytivirus of the family Iridoviridae is composed of two distinct species, namely, infectious spleen and kidney necrosis virus (ISKNV) and scale drop disease virus (SDDV), and both are important causative agents in a variety of bony fish worldwide. Of them, the ISKNV species is subdivided into three genotypes, namely, red seabream iridovirus (RSIV), ISKNV, and turbot reddish body iridovirus (TRBIV), and a further six subgenotypes, RSIV-I, RSIV-II, ISKNV-I, ISKNV-II, TRBIV-I, and TRBIV-II. Commercial vaccines derived from RSIV-I , RSIV-II and ISKNV-I have been available to several fish species. However, studies regarding the cross-protection effect among different genotype or subgenotype isolates have not been fully elucidated. In this study, RSIV-I and RSIV-II were demonstrated as the causative agents in cultured spotted seabass, Lateolabrax maculatus, through serial robust evidence, including cell culture-based viral isolation, whole-genome determination and phylogeny analysis, artificial challenge, histopathology, immunohistochemistry, and immunofluorescence as well as transmission electron microscope observation. Thereafter, a formalin-killed cell (FKC) vaccine generated from an ISKNV-I isolate was prepared to evaluate the protective effects against two spotted seabass original RSIV-I and RSIV-II. The result showed that the ISKNV-I-based FKC vaccine conferred almost complete cross-protection against RSIV-I and RSIV-II as well as ISKNV-I itself. No serotype difference was observed among RSIV-I, RSIV-II, and ISKNV-I. Additionally, the mandarin fish Siniperca chuatsi is proposed as an ideal infection and vaccination fish species for the study of various megalocytiviral isolates. IMPORTANCE Red seabream iridovirus (RSIV) infects a wide mariculture bony fish and has resulted in significant annual economic loss worldwide. Previous studies showed that the phenotypic diversity of infectious RSIV isolates would lead to different virulence characteristics, viral antigenicity, and vaccine efficacy as well as host range. Importantly, it is still doubted whether a universal vaccine could confer the same highly protective effect against various genotypic isolates. Our study here presented enough experimental evidence that a water in oil (w/o) formation of inactivated ISKNV-I vaccine could confer almost complete protection against RSIV-I and RSIV-II as well as ISKNV-I itself. Our study provides valuable data for better understanding the differential infection and immunity among different genotypes of ISKNV and RSIV isolates in the genus Megalocytivirus.
Serum bilirubin is associated with a reduced risk of subsequent recurrent wheezing following acute respiratory syncytial virus bronchiolitis

Bilirubin is a potent antioxidant and anti‐inflammatory molecule that has been shown to ameliorate airway inflammation. We aimed to study whether serum bilirubin is protective and can predict the development of subsequent recurrent wheezing in infants with severe respiratory syncytial virus (RSV) bronchiolitis.