Miracle-dz/UniFAR-FTUs huggingface dataset:
Remnant cholesterol is prospectively associated with cardiovascular disease events and all-cause mortality in kidney transplant recipients: the FAVORIT study

Background. The cholesterol content of circulating triglycer-ide-rich lipoproteins is characterized as remnant cholesterol, although little is known about its role in the development of cardiovascular disease (CVD) outcomes, all-cause mortality or transplant failure in kidney transplant recipients (KTRs). Our primary aim was to investigate the prospective association of remnant cholesterol and the risk of CVD events in renal transplant recipients with secondary aims evaluating remnant cholesterol and renal graft failure and all-cause mortality among participants in the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial. Methods. Among 4110 enrolled participants, 98 were excluded for missing baseline remnant cholesterol levels and covariates. Nonfasting remnant cholesterol levels were calculated based on the lipid profiles in 3812 FAVORIT trial participants at ran-domization. A Wilcoxon-type test for trend was used to compare baseline characteristics across remnant cholesterol quartiles. Cox proportional hazards regression was used to evaluate the association of baseline remnant cholesterol levels with time to primary and secondary study outcomes. Results. During a median follow-up of 4.0 years we docu-mented 548 CVD incident events, 343 transplant failures and 452 all-cause deaths. When comparing the highest quartile (quartile 4) to quartile 1, proportional hazard modeling revealed a significant increase in CVD risk f hazard ratio [HR] 1.32 [95% confidence interval (CI) 1.04–1.67] g and all-cause mortality risk [HR 1.34 (95% CI 1.01–1.69)]. A nonsignificant increase in transplant failure was seen as well [HR 1.20 (95% CI 0.87–1.64)]. Conclusions. Remnant cholesterol is associated with CVD and all-cause mortality in long-term KTRs. A randomized controlled clinical trial in KTRs that assesses the potential impact of remnant cholesterol-lowering therapy on these outcomes may be warranted.
Two countries, similar practices: the political practices of the food industry influencing the adoption of key public health nutrition policies in Guatemala and Panama

Abstract Objective: To identify the corporate political activity (CPA) strategies used by food industry actors during the development of two public health nutrition policies in Central America: Law #570 (taxation of sugar-sweetened beverages) in Panama and Bill #5504 (labelling and food marketing regulations) in Guatemala. Design: We triangulated data from publicly available information from 2018 to 2020, (e.g. industry and government materials; social media material) with semi-structured interviews with key stakeholders. Setting: Guatemala and Panama. Participants: Government, academia and international organisations workers in health and nutrition. Design: CPA strategies were categorised according to an existing internationally used taxonomy into action-based, instrumental strategies (coalition management, information management, direct involvement and influence in policy, legal action) and discursive strategies. Results: Instrumental strategies included the establishment of relationships with policymakers and direct lobbying against the proposed public policies. Discursive strategies were mainly criticising on the unfounded ground that they lacked evidence of effectiveness and will imply negative impacts on the economy. The industry pointed at individuals for making their own food choices, in order to shift the focus away from the role of its products in contributing to ill health. Conclusion: We provide evidence of the political practices used by the food industry to interfere with the development and implementation of public health nutrition policies to improve diets in Central America. Policymakers, public health advocates and the public should be informed about those practices and develop counterstrategies and arguments to protect the public and policies from the vested interests of the food industry.
The relationship between client dissatisfaction and contraceptive discontinuation among urban family planning clients in three sub-Saharan African countries

Although researchers and practitioners have suggested that the quality of family planning services impacts contraceptive discontinuation, establishing a causal relationship has been challenging, primarily due to data limitations and a lack of agreement on how to measure quality. This longitudinal study estimated the relationship of the dissatisfaction with family planning services on contraceptive discontinuation for a sample of 797 female clients who sought family planning services at urban facilities across Kenya, Nigeria, and Burkina Faso. Clients who sought family planning services were first interviewed in person at private and public health facilities and received a follow-up phone interview four to six months later. In our sample, 18.2% of clients who were using a modern contraceptive at baseline stopped using it by follow-up. At baseline, nearly 14% of clients reported experiencing a problem with service convenience, nearly 12% with the availability of medicines and contraceptives, and nearly 6% with facility cleanliness and/or staff treatment. We hypothesized that client dissatisfaction with the family planning services received informed their decision to discontinue contraception and estimated univariate and bivariate probit regression models, controlling for individual and health facility characteristics. We found that client’s perceptions of staff treatment and facility cleanliness informed their expectations about service and contraceptive standards, affecting subsequent contraceptive discontinuation. The difference in the probability of discontinuing contraception was 8.2 percentage-points between dissatisfied and satisfied clients. Examining client dissatisfaction with family planning services can inform the family planning community on needed improvements to increase contraceptive adherence for women in need, which can prevent unplanned pregnancies and unwanted births in the long run.
Changing allometric relationships among fossil and Recent populations in two colonial species

Allometry is vital for understanding the mechanisms underlying phenotypic evolution. Despite a large body of literature on allometry, studies based on fossil time series are limited for solitary organisms and nonexistent for colonial organisms. Allometric relationships have been found to be relatively constant across Recent populations of the same species, separated by space, but variable among fossil populations separated by thousands of years. How stable are allometric relationships at the module level for colonial organisms? We address this question using two extant species of the cheilostome bryozoan Microporella with fossil records spanning the Pleistocene of New Zealand. We investigate size covariation between feeding modules and three traits with separate functions (reproductive, resource uptake, and defense). We found that within‐population (static) allometry can change on timescales of at least 0.1 million years. These within‐population relationships do not consistently predict overintraspecific evolutionary allometry, which in turn does not predict those estimated at the genus level. Different functional traits are constrained to different extents by module size with defensive traits being the least constrained and most evolvable, compared with reproductive and resource uptake traits. Our study highlights the potential of colonial organisms in understanding the constraints and drivers of long‐term phenotypic change.
Common and unique neural mechanisms of social and nonsocial conflict resolving and adaptation

Abstract Humans often need to deal with various forms of information conflicts that arise when they receive inconsistent information. However, it remains unclear how we resolve them and whether the brain may recruit similar or distinct brain mechanisms to process different domains (e.g. social vs. nonsocial) of conflicts. To address this, we used functional magnetic resonance imaging and scanned 50 healthy participants when they were asked to perform 2 Stroop tasks with different forms of conflicts: social (i.e. face–gender incongruency) and nonsocial (i.e. color–word incongruency) conflicts. Neuroimaging results revealed that the ventral lateral prefrontal cortex was generally activated in processing incongruent versus congruent stimuli regardless of the task type, serving as a common mechanism for conflict resolving across domains. Notably, trial-based and model-based results jointly demonstrated that the dorsal and rostral medial prefrontal cortices were uniquely engaged in processing social incongruent stimuli, suggesting distinct neural substrates of social conflict resolving and adaptation. The findings uncover that the common but unique brain mechanisms are recruited when humans resolve and adapt to social conflicts.
Increased expression and accumulation of GDF15 in IPF extracellular matrix contribute to fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic disease of unmet medical need. It is characterized by formation of scar tissue leading to a progressive and irreversible decline in lung function. IPF is associated with repeated injury, which may alter the composition of the extracellular matrix (ECM). Here, we demonstrate that IPF patient–derived pulmonary ECM drives profibrotic response in normal human lung fibroblasts (NHLF) in a 3D spheroid assay. Next, we reveal distinct alterations in composition of the diseased ECM, identifying potentially novel associations with IPF. Growth differentiation factor 15 (GDF15) was identified among the most significantly upregulated proteins in the IPF lung–derived ECM. In vivo, GDF15 neutralization in a bleomycin-induced lung fibrosis model led to significantly less fibrosis. In vitro, recombinant GDF15 (rGDF15) stimulated α smooth muscle actin (αSMA) expression in NHLF, and this was mediated by the activin receptor-like kinase 5 (ALK5) receptor. Furthermore, in the presence of rGDF15, the migration of NHLF in collagen gel was reduced. In addition, we observed a cell type–dependent effect of GDF15 on the expression of cell senescence markers. Our data suggest that GDF15 mediates lung fibrosis through fibroblast activation and differentiation, implicating a potential direct role of this matrix-associated cytokine in promoting aberrant cell responses in disease.
The evolving treatment of congenital heart disease in patient with Down syndrome: Current state of knowledge

Children with Down syndrome are usually seen as not worthy of high‐risk cardiac surgery. Through this review, we try to show the results of curative and palliative surgery for functional single ventricle syndrome in patients with Down syndrome, as there is currently no standard protocol for the treatment of this category of patients.
Anterior mandibular alveolar bone measurements between diabetic and non-diabetic individuals using cone-beam computed tomography.

OBJECTIVE An adequate alveolar facial bone thickness (FBT) and facial bone height (FBH) in the mandibular anterior region is essential for implant placement. However, the diabetic condition may affect FBT and FBH. The aim of the study is to compare the alveolar FBT and FBH in the anterior mandibular region of diabetic and non-diabetic individuals utilizing Cone Beam Computed Tomography (CBCT) images. MATERIALS AND METHODS This cross-sectional study was conducted in dental clinics of Riyadh Elm University, Riyadh, Saudi Arabia. A total of 46 CBCT images belonging to the diabetic (n=23) and non-diabetic (n=23) individuals were obtained from the radiographic image database of the hospital. The alveolar FBT and FBH in the anterior mandibular region were measured directly on CBCT images using Galileos 3D Digital Imaging System in Sagittal and cross-sectional view. RESULTS The comparison of mean FBT between non-diabetic and diabetic individuals in central incisors (0.96±0.25 vs. 0.79±0.24, p=0.025) and lateral incisors (1.00±0.23 vs. 0.78±0.17, p=0.001) showed a statistically significant difference. Similarly, the mean FBH between non-diabetic and diabetic individuals differed significantly in central (31.37.96±2.98 vs. 26.07±6.58, p=0.001) and lateral incisor (31.20±3.05 vs. 26.79±6.83, p=0.008) regions. CONCLUSIONS Based on our study, non-diabetic individuals showed higher alveolar FBT and FBH levels than diabetic individuals. Hence, diabetic condition affects the alveolar FBT and FBH around the central and lateral incisor regions.
Dose-Dependent Hepacivirus Infection Reveals Linkage between Infectious Dose and Immune Response

We demonstrate that the EqHV dose of infection plays an important role for inducing immune responses, possibly linked to early clearance in high-dose and prolonged viremia in low-dose infections. In particular, pathways associated with innate and adaptive immune responses, as well as inflammatory responses, were more strongly upregulated in high-dose infections than in lower doses. ABSTRACT More than 70 million people worldwide are still infected with the hepatitis C virus 30 years after its discovery, underscoring the need for a vaccine. To develop an effective prophylactic vaccine, detailed knowledge of the correlates of protection and an immunocompetent surrogate model are needed. In this study, we describe the minimum dose required for robust equine hepacivirus (EqHV) infection in equids and examined how this relates to duration of infection, seroconversion, and transcriptomic responses. To investigate mechanisms of hepaciviral persistence, immune response, and immune-mediated pathology, we inoculated eight EqHV naive horses with doses ranging from 1–2 copies to 1.3 × 106 RNA copies per inoculation. We characterized infection kinetics, pathology, and transcriptomic responses via next generation sequencing. The minimal infectious dose of EqHV in horses was estimated at 13 RNA copies, whereas 6 to 7 copies were insufficient to cause infection. Peak viremia did not correlate with infectious dose, while seroconversion and duration of infection appeared to be affected. Notably, seroconversion was undetectable in the low-dose infections within the surveillance period (40 to 50 days). In addition, transcriptomic analysis revealed a nearly dose-dependent effect, with greater immune activation and inflammatory response observed in high-dose infections than in low-dose infections. Interestingly, inoculation with 6–7 copies of RNA that did not result in productive infection, but was associated with a strong immune response, similar to that observed in the high-dose infections. IMPORTANCE We demonstrate that the EqHV dose of infection plays an important role for inducing immune responses, possibly linked to early clearance in high-dose and prolonged viremia in low-dose infections. In particular, pathways associated with innate and adaptive immune responses, as well as inflammatory responses, were more strongly upregulated in high-dose infections than in lower doses. Hence, inoculation with low doses may enable EqHV to evade strong immune responses in the early phase and therefore promote robust, long-lasting infection.
BmCH25H, a vertebrate interferon‐stimulated gene(ISG) homolog, inhibits BmNPV infection dependent on its hydroxylase activity in Bombyx mori

Cholesterol‐25‐hydroxylase (CH25H) has been identified as an interferon‐stimulated gene (ISG) in mammals that exerts its antiviral effects by catalyzing the conversion of cholesterol to 25‐hydroxycholesterol (25HC). However, invertebrates lack an antiviral system homologous to vertebrate interferons (IFNs) because the genomes of invertebrates do not encode IFN‐like cytokines. Nevertheless, CH25H is present in insect genomes and it therefore deserves further study of whether and by which mechanism it could exert an antiviral effect in invertebrates. In this study, the Bombyx mori CH25H (BmCH25H) gene, of which the encoded protein has high homology with other lepidopteran species, was identified and located on chromosome 9. Interestingly, we found that the expression of BmCH25H was significantly upregulated in B. mori nucleopolyhedrovirus (BmNPV) ‐infected BmN cells and silkworm (B. mori) larvae at the early infection stage. The inhibitory effect of BmCH25H on BmNPV replication was further demonstrated to depend on its catalytic residues to convert cholesterol to 25HC. More importantly, we demonstrated that during BmNPV infection, BmCH25H expression was increased through the Janus kinase–signal transducer and activator of transcription (JAK–STAT) pathway, similar to the induction of ISGs following virus infection in vertebrates. This is the first report that CH25H has antiviral effects in insects; the study also elucidates the regulation of its expression and its mechanism of action.
Interdisciplinary in silico studies to understand in-depth molecular level mechanism of drug resistance involving NS3-4A protease of HCV

Abstract Hepatitis C virus (HCV) causes hepatitis, a life-threatening disease responsible for liver cirrhosis. Urgent measures have been taken to develop therapeutics against this deadly pathogen. NS3/4A protease is an extremely important target. A series of inhibitors have been developed against this viral protease including Faldaprevir. Unfortunately, the error-prone viral RNA polymerase causes the emergence of resistance, thereby causing reduced effectiveness of those peptidomimetic inhibitors. Among the drug resistant variants, three single amino acid residues (R155, A156 and D168) are notable for their presence in clinical isolates and also their effectivity against most of the known inhibitors in clinical development. Therefore, it is crucial to understand the mechanistic role of those drug resistant variants while designing potent novel inhibitors. In this communication, we have deeply analyzed through using in silico studies to understand the molecular mechanism of alteration of inhibitor binding between wild type and its R155K, A156V and D168V variants. Principal component analysis was carried to identify the backbone fluctuations of important residues in HCV NS3/4A responsible for the inhibitor binding and maintaining drug resistance. Free energy landscape as a function of the principal components has been used to identify the stability and conformation of the key residues that regulate inhibitor binding and their impact in developing drug resistance. Our findings are consistent with the trend of experimental results. The observations are also true in case of other Faldaprevir-like peptidomimetic inhibitors. Understanding this binding mechanism would be significant for the development of novel inhibitors with less susceptibility towards drug resistance. Communicated by Ramaswamy H. Sarma Graphical Abstract
Draping in Dermatology: A Patient’s Perspective

Background/Objectives Patient dignity is a core component of the Canadian health care system; however, there may be challenges to maintaining patient dignity in clinical settings requiring total body skin examination (TBSE) for adequate assessment and diagnosis. As standardized TBSE draping practices have not been investigated in a dermatology setting, we sought out to investigate subjective patient experiences of draping practices. Methods A cross-sectional study was performed using a paper survey in dermatology hospital clinics over a 6-month period to 150 patients. Results Draping was considered important by over 50% of patients surveyed (54.7%). Respondents who indicated that draping impacted their comfort level “a lot” or “very much” had a mean age of 52 and were more likely to be females (P < .05). Females were also more likely to answer that their body weight/shape (P < .05), physician of same (P < .01) or opposite sex (P < .001), and the degree of privacy offered by drapes (P < .001) impacted their comfort level when undressing for a TBSE. Respondents who reported that any assessed factor impacted their comfort during a TBSE were also younger (P < .05), suggesting that younger and female patients were more likely to have comfort concerns than males. Conclusions Our study confirmed that most patients surveyed considered draping to be important. Our findings highlight the importance of adequate draping practices to maintain patient privacy and dignity for all patients, with special attention to younger female patients to ensure they feel as comfortable as possible. Future research should focus on how these identified patient comfort factors can be implemented into medical education.
Genetic predisposition to porto‐sinusoidal vascular disorder: A functional genomic‐based, multigenerational family study

Background and Aims: Porto‐sinusoidal vascular disorder (PSVD) is a group of liver vascular diseases featuring lesions encompassing the portal venules and sinusoids unaccompanied by cirrhosis, irrespective of the presence/absence of portal hypertension. It can occur secondary to coagulation disorders or insult by toxic agents. However, the cause of PSVD remains unknown in most cases. Hereditary cases of PSVD are exceptionally rare, but they are of particular interest and may unveil genetic alterations and molecular mechanisms associated with the disease. Approach and Results: We performed genome sequencing of four patients and two healthy individuals of a large multigenerational Lebanese family with PSVD and identified a heterozygous deleterious variant (c.547C>T, p.R183W) of FCH and double SH3 domains 1 (FCHSD1), an uncharacterized gene, in patients. This variant segregated with the disease, and its pattern of inheritance was suggestive of autosomal dominant with variable expressivity. RNA structural modelling of human FCHSD1 suggests that the C‐to‐T substitution at position 547, corresponding to FCHSD1 R183W , may increase both messenger RNA (mRNA) and protein stability and its interaction with MTOR‐associated protein, LST8 homolog, a key protein of the mechanistic target of rapamycin (mTOR pathway). These predictions were substantiated by biochemical analyses, which showed that FCHSD1 R183W induced high FCHSD1 mRNA stability, overexpression of FCHSD1 protein, and an increase in mTORC1 activation. This human FCHSD1 variant was introduced into mice through CRISPR/Cas9 genome editing. Nine out of the 15 mice carrying the human FCHSD1 R183W variant mimicked the phenotype of human PSVD, including splenomegaly and enlarged portal vein. Conclusions: Aberrant FCHSD1 structure and function leads to mTOR pathway overactivation and may cause PSVD.