Miracle-dz/UniFAR-FTUs huggingface dataset:
Cadherin and Wnt signaling pathways as key regulators in diabetic nephropathy

Aim A recent meta-analysis of genome-wide linkage studies (GWLS) has identified multiple genetic regions suggestive of linkage with DN harboring hundreds of genes. Moving this number of genetic loci forward into biological insight is truly the next step. Here, we approach this challenge with a gene ontology (GO) analysis in order to yield biological and functional role to the genes, an over-representation test to find which GO terms are enriched in the gene list, pathway analysis, as well as protein network analysis. Method GO analysis was performed using protein analysis through evolutionary relationships (PANTHER) version 14.0 software and P-values less than 0.05 were considered statistically significant. GO analysis was followed by over-representation test for the identification of enriched terms. Statistical significance was calculated by Fisher’s exact test and adjusted using the false discovery rate (FDR) for correction of multiple tests. Cytoscape with the relevant plugins was used for the construction of the protein network and clustering analysis. Results The GO analysis assign multiple GO terms to the genes regarding the molecular function, the biological process and the cellular component, protein class and pathway analysis. The findings of the over-representation test highlight the contribution of cell adhesion regarding the biological process, integral components of plasma membrane regarding the cellular component, chemokines and cytokines with regard to protein class, while the pathway analysis emphasizes the contribution of Wnt and cadherin signaling pathways. Conclusions Our results suggest that a core feature of the pathogenesis of DN may be a disturbance in Wnt and cadherin signaling pathways, whereas the contribution of chemokines and cytokines need to be studied in additional studies.
Genome scans of facial features in East Africans and cross-population comparisons reveal novel associations

Facial morphology is highly variable, both within and among human populations, and a sizable portion of this variation is attributable to genetics. Previous genome scans have revealed more than 100 genetic loci associated with different aspects of normal-range facial variation. Most of these loci have been detected in Europeans, with few studies focusing on other ancestral groups. Consequently, the degree to which facial traits share a common genetic basis across diverse sets of humans remains largely unknown. We therefore investigated the genetic basis of facial morphology in an East African cohort. We applied an open-ended data-driven phenotyping approach to a sample of 2,595 3D facial images collected on Tanzanian children. This approach segments the face into hierarchically arranged, multivariate features that capture the shape variation after adjusting for age, sex, height, weight, facial size and population stratification. Genome scans of these multivariate shape phenotypes revealed significant (p < 2.5 × 10−8) signals at 20 loci, which were enriched for active chromatin elements in human cranial neural crest cells and embryonic craniofacial tissue, consistent with an early developmental origin of the facial variation. Two of these associations were in highly conserved regions showing craniofacial-specific enhancer activity during embryological development (5q31.1 and 12q21.31). Six of the 20 loci surpassed a stricter threshold accounting for multiple phenotypes with study-wide significance (p < 6.25 × 10−10). Cross-population comparisons indicated 10 association signals were shared with Europeans (seven sharing the same associated SNP), and facilitated fine-mapping of causal variants at previously reported loci. Taken together, these results may point to both shared and population-specific components to the genetic architecture of facial variation.
Sobp modulates the transcriptional activation of Six1 target genes and is required during craniofacial development.

Branchio-oto-renal syndrome (BOR) is a disorder characterized by hearing loss, craniofacial and/or renal defects. Variants in the transcription factor Six1 and its cofactor Eya1, both required for otic development, are linked to BOR. We previously identified Sobp as a potential Six1 cofactor and SOBP variants in mouse and humans cause otic phenotypes; therefore, we asked whether Sobp interacts with Six1 and thereby may contribute to BOR. Co-IP and immunofluorescence experiments demonstrate that Sobp binds to and co-localizes with Six1 in the cell nucleus. Luciferase assays show that Sobp interferes with the transcriptional activation of Six1+Eya1 target genes. Experiments in Xenopus embryos that either knockdown or increase expression show that Sobp is required for formation of ectodermal domains at neural plate stages. In addition, altering Sobp levels disrupts otic vesicle development and causes craniofacial cartilage defects. Expression of Xenopus Sobp containing the human variant disrupts the pre-placodal ectoderm similar to full-length Sobp, but other changes are distinct. These results indicate that Sobp modifies Six1 function, is required for vertebrate craniofacial development, and identifies Sobp as a potential candidate gene for BOR.
Risk factors for developing peritoneal metastases after curative surgery for colorectal cancer: A systematic review and meta‐analysis

Proactive detection and treatment strategies have achieved encouraging survival outcomes for patients with early peritoneal metastases (PM), but these costly and invasive approaches can only be applied to selected high‐risk patients. This meta‐analysis aimed to identify the risk factors for metachronous PM after curative surgery for colorectal cancer (CRC).
A machine learning approach to predict extreme inactivity in COPD patients using non-activity-related clinical data

Facilitating the identification of extreme inactivity (EI) has the potential to improve morbidity and mortality in COPD patients. Apart from patients with obvious EI, the identification of a such behavior during a real-life consultation is unreliable. We therefore describe a machine learning algorithm to screen for EI, as actimetry measurements are difficult to implement. Complete datasets for 1409 COPD patients were obtained from COLIBRI-COPD, a database of clinicopathological data submitted by French pulmonologists. Patient- and pulmonologist-reported estimates of PA quantity (daily walking time) and intensity (domestic, recreational, or fitness-directed) were first used to assign patients to one of four PA groups (extremely inactive [EI], overtly active [OA], intermediate [INT], inconclusive [INC]). The algorithm was developed by (i) using data from 80% of patients in the EI and OA groups to identify ‘phenotype signatures’ of non-PA-related clinical variables most closely associated with EI or OA; (ii) testing its predictive validity using data from the remaining 20% of EI and OA patients; and (iii) applying the algorithm to identify EI patients in the INT and INC groups. The algorithm’s overall error for predicting EI status among EI and OA patients was 13.7%, with an area under the receiver operating characteristic curve of 0.84 (95% confidence intervals: 0.75–0.92). Of the 577 patients in the INT/INC groups, 306 (53%) were reclassified as EI by the algorithm. Patient- and physician- reported estimation may underestimate EI in a large proportion of COPD patients. This algorithm may assist physicians in identifying patients in urgent need of interventions to promote PA.
Diagnostic testing holds the key to NTD elimination

“Fit-for-purpose” diagnostic tests have emerged as a prerequisite to achieving global targets for the prevention, control, elimination, and eradication of neglected tropical diseases (NTDs), as highlighted by the World Health Organization’s (WHO) new roadmap. There is an urgent need for the development of new tools for those diseases for which no diagnostics currently exist and for improvement of existing diagnostics for the remaining diseases. Yet, efforts to achieve this, and other crosscutting ambitions, are fragmented, and the burden of these 20 debilitating diseases immense. Compounded by the Coronavirus Disease 2019 (COVID-19) pandemic, programmatic interruptions, systemic weaknesses, limited investment, and poor commercial viability undermine global efforts—with a lack of coordination between partners, leading to the duplication and potential waste of scant resources. Recognizing the pivotal role of diagnostic testing and the ambition of WHO, to move forward, we must create an ecosystem that prioritizes country-level action, collaboration, creativity, and commitment to new levels of visibility. Only then can we start to accelerate progress and make new gains that move the world closer to the end of NTDs.
Exploring feedback‐controlled versus open‐circuit electrochemical lipolysis in ex vivo and in vivo porcine fat: A feasibility study

Minimally invasive fat sculpting techniques are becoming more widespread with the development of office‐based devices and therapies. Electrochemical lipolysis (ECLL) is a needle‐based technology that uses direct current (DC) to electrolyze tissue water creating acid and base in situ. In turn, fat is saponified and adipocyte cell membrane lysis occurs. The electrolysis of water can be accomplished using a simple open‐loop circuit (V‐ECLL) or by incorporating a feedback control circuit using a potentiostat (P‐ECLL). A potentiostat utilizes an operational amplifier with negative feedback to allow users to precisely control voltage at specific electrodes. To date, the variation between the two approaches has not been studied. The aim of this study was to assess current and charge transfer variation and lipolytic effect created by the two approaches in an in vivo porcine model.
Surface Engineering of TiO2 ETL for Highly Efficient and Hysteresis‐Less Planar Perovskite Solar Cell (21.4%) with Enhanced Open‐Circuit Voltage and Stability

Interfacial studies and band alignment engineering on the electron transport layer (ETL) play a key role for fabrication of high‐performance perovskite solar cells (PSCs). Here, an amorphous layer of SnO2 (a‐SnO2) between the TiO2 ETL and the perovskite absorber is inserted and the charge transport properties of the device are studied. The double‐layer structure of TiO2 compact layer (c‐TiO2) and a‐SnO2 ETL leads to modification of interface energetics, resulting in improved charge collection and decreased carrier recombination in PSCs. The optimized device based on a‐SnO2/c‐TiO2 ETL shows a maximum power conversion efficiency (PCE) of 21.4% as compared to 19.33% for c‐TiO2 based device. Moreover, the modified device demonstrates a maximum open‐circuit voltage (Voc) of 1.223 V with 387 mV loss in potential, which is among the highest reported value for PSCs with negligible hysteresis. The stability results show that the device on c‐TiO2/a‐SnO2 retains about 91% of its initial PCE value after 500 h light illumination, which is higher than pure c‐TiO2 (67%) based devices. Interestingly, using a‐SnO2/c‐TiO2 ETL the PCE loss was only 10% of initial value under continuous UV light illumination after 30 h, which is higher than that of c‐TiO2 based device (28% PCE loss).
Social choice using moral metrics

PurposeThis paper aims to develop a geometry of moral systems. Existing social choice mechanisms predominantly employ simple structures, such as rankings. A mathematical metric among moral systems allows us to represent complex sets of views in a multidimensional geometry. Such a metric can serve to diagnose structural issues, test existing mechanisms of social choice or engender new mechanisms. It also may be used to replace active social choice mechanisms with information-based passive ones, shifting the operational burden.Design/methodology/approachUnder reasonable assumptions, moral systems correspond to computational black boxes, which can be represented by conditional probability distributions of responses to situations. In the presence of a probability distribution over situations and a metric among responses, codifying our intuition, we can derive a sensible metric among moral systems.FindingsWithin the developed framework, the author offers a set of well-behaved candidate metrics that may be employed in real applications. The author also proposes a variety of practical applications to social choice, both diagnostic and generative.Originality/valueThe proffered framework, derived metrics and proposed applications to social choice represent a new paradigm and offer potential improvements and alternatives to existing social choice mechanisms. They also can serve as the staging point for research in a number of directions.
Antidepressant Discontinuation

Abstract Background The topic of patients’ discontinuing use of antidepressants has received increasing attention. Patients and physicians can encounter challenges regarding the three major questions in the field of antidepressant discontinuation: who can discontinue, what is the best time to discontinue; and what is the best method to discontinue. Methods This commentary summarizes the current state of the evidence related to antidepressant discontinuation. Results There is limited evidence underlying the extremely relevant clinical topic of antidepressant discontinuation. It is poorly understood which patients, after response to antidepressants, benefit (most) from discontinuation. Moreover, established and validated markers of an individual’s risk of relapse after antidepressant cessation are lacking, and non-sponsored discontinuation studies are rare. Many discontinuation studies do not distinguish between relapse and antidepressant discontinuation symptoms, and very few studies compared different discontinuation strategies, with none of the compared strategies exceeding 2 weeks of tapering. Finally, blinding of discontinuation strategies is often insufficient to properly address placebo and nocebo aspects, whereas the pharmacological characteristics of different antidepressants in relation to discontinuation have hardly been studied. Conclusions Antidepressant discontinuation is a clinically relevant topic. There is a strong need for more robust evidence to indicate who can discontinue antidepressants, when and in which manner (how). Blinded randomized controlled trials are pivotal to optimally advise physicians, patients and policy-makers. This scientific knowledge can guide evidence-based decision making in clinical practice.
Comprehensively feature-based molecular networking and metabolomics approaches to reveal the differences components in Cinnamomum cassia and Cinnamomum verum.

Cinnamon was been a widely used plant in medicinal and spices for a long time and has spread all over the world. However, the differences in the components of the bark from Cinnamomum cassia and Cinnamomum verum, two most common types of cinnamon, have not been thoroughly investigated. In the present experiment, ultra-high-performance liquid chromatography LTQ-Orbitrap Velos Pro hybrid mass spectrometer-based metabolomics coupled with chemometrics and feature-based molecular networking were employed to dramatically distinguish and annotate of Cinnamomum cassia Bark and Cinnamomum verum Bark. As consequences, principal component analysis, orthogonal projection to latent structures discriminates analysis and heat map analysis demonstrated a clear discrimination between the profiles of metabolites in cinnamon. Besides, as the known compounds, proanthocyanidins (cinnamtannin B1 and procyanidin B2) and alkaloids (norboldine, norisoboldine) with variable importance in the projection scores > 6, and an unknown alkaloid (formula C24 H33 NO6 ) were selected as the best markers to discriminate cinnamon. Furthermore, large numbers of proanthocyanidins and alkaloids components were identified through feature-based molecular networking for the first time. Our investigation provides new ideas for the discovery of quality markers and identification of unknown components in natural products. This article is protected by copyright. All rights reserved.
D-(-)-POly-13-Hydroxybutyrate in Membranes of Genetically

D-(-)-Poly-3-hydroxybutyrate is a constituent of the membranes and the cytoplasms of genetically competent Azotobacter vinelandii, Bacillus subtilis, and Haemophilus influenzae cells. Within each species the concentration of D-(-)poly-,l-hydroxybutyrate in the membranes and cytoplasm correlates with transformability. Fluorescence analysis of the thermotropic lipid phase transitions in A. vinelandii and B. subtilis cells indicates that D-(-)-poly-p-hydroxybutyrate forms an organized gel structure in the membranes which is very labile. The concentration of organized D-(-)-poly-p-hydroxybutyrate in the membranes, which can be estimated from the intensity of its phase transition, can be used to assess the competence of a culture.
.ftr4, That Is Needed for Cell Cycle Timing of fluE Operon

ThefliF operon of Caulobacter crescentus, which was previously designated theflaO locus, is near the top of the flagellar-gene regulatory hierarchy, and it is one of the earliest transcription units to be expressed in the cell cycle. In this report, we have identified two cis-acting sequences that are required for cell cycle regulation of fliF transcription. The first sequence was defined by the effects of three 2-bp deletions and five point mutations, each ofwhich greatly reduced the level offliF operon transcript in vivo. These eight mutations lie between -37 and -22 within an 18-bp sequence that matches, at 11 nucleotides, sequences in the 5' regions oftheflaQR ((laS locus) andfliLM operons, which are also expressed early and occupy a high level in the regulatory hierarchy (A. Dingwall, A. Zhuang, K. Quon, and L. Shapiro, J. Bacteriol. 174:1760-1768, 1992). We propose that this 18-bp sequence contains all or part of thefliF promoter. We have also identified a second sequence, 17 bp long and centered at -8, which we have provisionally designatedftr4 because of its similarity to the enhancer-like fir sequences required for regulation of o4 promotersfiaN andflbG (D. A. Mullin and A. Newton, J. Bacteriol. 171:3218-3227, 1989). Six of the seven mutations inftr4 examined resulted in a large increase infliF operon transcript levels, suggesting a role forftr4 in negative regulation. A 2-bp deletion at -12 and -13 inftr4 altered the cell cycle pattern offliF operon transcription; the transcript was still expressed periodically, but the period of its synthesis was extended significantly. We suggest that theftr4 sequence may form part of a developmental switch which is required to turn offliF operon transcription at the correct time in the cell cycle.
A phenomenological study on older persons as a breadwinner of A skipped-generation family: day by day coping journey in Thai context

ABSTRACT Purpose: Many countries around the world are facing an ageing society in which older persons share the fate of carrying a burden in their families, especially in skipped-generation families. This increasing trend has noted over the past several years in Thailand. This is an interpretive phenomenological study that seeks to explore Thai older grandparents’ life experience of raising grandchildren in skipped-generation families. Methods: The participants were purposively selected from older grandparents in skipped-generation families in the Northeast of Thailand in 2019. Data were collected by in-depth interviews with 29 participants. Data were analysed using Diekelmann & Allen method. Results: Three major themes emerged regarding the Thai older persons as a breadwinner of a skipped-generation family were as follows. 1) Sacrifice for the family is a value of life. 2) Day by day coping journey of individuals maintains mental well-being. 3) Being grandparents leads to spiritual pride. Conclusion: The older grandparents suffered from a variety of burden and vulnerability beyond their abilities. Social and governmental supporting systems are limited. Creating supporting system strategy is required to increase well-being of grandparents in skipped-generation families.
Regional variation in lateral and medial gastrocnemius muscle fibre lengths obtained from diffusion tensor imaging

Assessment of regional muscle architecture is primarily done through the study of animals, human cadavers, or using b‐mode ultrasound imaging. However, there remain several limitations to how well such measurements represent in vivo human whole muscle architecture. In this study, we developed an approach using diffusion tensor imaging and magnetic resonance imaging to quantify muscle fibre lengths in different muscle regions along a muscle's length and width. We first tested the between‐day reliability of regional measurements of fibre lengths in the medial (MG) and lateral gastrocnemius (LG) and found good reliability for these measurements (intraclass correlation coefficient [ICC] = 0.79 and ICC = 0.84, respectively). We then applied this approach to a group of 32 participants including males (n = 18), females (n = 14), young (24 ± 4 years) and older (70 ± 2 years) adults. We assessed the differences in regional muscle fibre lengths between different muscle regions and between individuals. Additionally, we compared regional muscle fibre lengths between sexes, age groups, and muscles. We found substantial variability in fibre lengths between different regions within the same muscle and between the MG and the LG across individuals. At the group level, we found no difference in mean muscle fibre length between males and females, nor between young and older adults, or between the MG and the LG. The high variability in muscle fibre lengths between different regions within the same muscle, possibly expands the functional versatility of the muscle for different task requirements. The high variability between individuals supports the use of subject‐specific measurements of muscle fibre lengths when evaluating muscle function.
Legacy of a 10-Year Multidomain Lifestyle Intervention on the Cognitive Trajectories of Individuals with Overweight/Obesity and Type 2 Diabetes Mellitus

Introduction: Weight loss and increased physical activity interventions are commonly recommended for individuals with type 2 diabetes (T2D) and overweight or obesity. We examined the impact of randomization to an intensive lifestyle intervention (ILI) on trajectories of cognitive function over 10 years in a cohort of participants in a randomized clinical trial who had T2D and overweight/obesity at baseline. Methods: Participants aged 45–76 years were enrolled in 2001–2004 and were randomized to the ILI or a diabetes support and education (DSE) condition. Cognitive function was assessed in 3,938 participants at up to 4 time points 8–18 years after randomization. General linear mixed effects models examined cognitive trajectories over time. Subgroup analyses focused on sex, individuals with baseline body mass index >30, those carrying the APOE ε4 allele, and those with a baseline history of cardiovascular disease (CVD). Results: Overall, there were no differences in the rate of cognitive decline by intervention arm. Subgroup analyses showed that participants who had a baseline history of CVD and were randomized to the ILI arm of the study performed significantly worse on the Stroop Color Word Test than those in the DSE arm. Discussion/Conclusions: The ILI did not result in preserved cognitive function or slower rates of cognitive decline in this cohort of individuals who had T2D and were overweight or obese at baseline.