Miracle-dz/UniFAR-FTUs huggingface dataset:
Altering enhancer-promoter linear distance impacts promoter competition in cis and in trans.

In Drosophila, pairing of maternal and paternal homologs can permit trans-interactions between enhancers on one homolog and promoters on another, an example of a phenomenon called transvection. When chromosomes are paired, promoters in cis and in trans to an enhancer can compete for the enhancer's activity, but the parameters that govern this competition are as yet poorly understood. To assess how the linear spacing between an enhancer and promoter can influence promoter competition in Drosophila, we employed transgenic constructs wherein the eye-specific enhancer GMR is placed at varying distances from a heterologous hsp70 promoter driving a fluorescent reporter. While GMR activates the reporter to a high degree when the enhancer and promoter are spaced by a few hundred base pairs, activation is strongly attenuated when the enhancer is moved 3 kilobases away. By examining transcription of endogenous genes near the point of transgene insertion, we show that linear spacing of 3 kb between GMR and the hsp70 promoter results in elevated transcription of neighboring promoters, suggesting a loss of specificity between the enhancer and its intended transgenic target promoter. Furthermore, increasing spacing between GMR and hsp70 by just 100 bp can enhance transvection, resulting in increased activation of a promoter on a paired homolog at the expense of a promoter in cis to the enhancer. Finally, cis-/trans-promoter competition assays in which one promoter carries mutations to key core promoter elements show that GMR will skew its activity toward a wild type promoter, suggesting that an enhancer is in a balanced competition between its potential target promoters in cis and in trans.
Shame, stigma, and social exclusion: The lived experiences of epileptic patients in a health facility in Ilorin, Nigeria

ABSTRACT Background The highest number of persons living with epilepsy (PLWE) are in Africa and the majority live in deplorable conditions, while dealing with varying layers of stigma, social exclusion, and discrimination. Objective This study explored the lived experiences of PLWE in Ilorin. Methods Adopting a qualitative design and a phenomenological lens, 10 PLWE between the ages of 18 and 60 were purposively selected from the University of Ilorin Teaching Hospital (UITH) for in-depth interviews. Results Findings suggest that PLWE bear multiple and intersecting burdens, including physical injuries; institutional, cultural, and economic constraints; psychological strain; social exclusion; and stigma. These disadvantages are often sustained and reproduced by various assumptions about epilepsy; as such, PLWE conceal their condition, and this implicatively reinforce stigma. Difficulty sustaining intimate relationships, overt physical scars, and inferiority complexes are recurrent challenges for PLWE. The study showed that adherence to drugs, self-management, personal precautions towards seizure signs, and family support are important coping strategies. Conclusion The study recommends that it is imperative to enhance and sustain systems, processes, and attitudes that prioritise the physical, social, and emotional needs of PLWE, because this is significant for their enhanced quality of life (QoL).
Socio-culturally adapted educational videos increase maternal and newborn health knowledge in pregnant women and female community health volunteers in Nepal’s Khotang district

Objectives: While Nepal has made significant improvements in maternal and newborn health overall, the lack of maternal and newborn health–related knowledge in the more rural parts of the country has led to significant disparities in terms of both maternal and newborn health service utilization and maternal and newborn health outcomes. This study aimed to assess whether viewing culturally adapted maternal and newborn health educational films had a positive impact on (1) the maternal and newborn health knowledge levels among pregnant women and (2) the postpartum hemorrhage–related knowledge levels among Female Community Health Volunteers in rural Nepal. Methods: Four locations were selected for their remoteness and comparatively high number of pregnancies. A convenience sample of 101 pregnant women and 39 Female Community Health Volunteers were enrolled in the study. A pre- and post-test design was employed to assess this intervention. Paired t-tests were used to analyze the change in number of correct responses by knowledge domain for multi-film participants, producing a numeric “mean knowledge score,” and McNemar’s tests were used to calculate the change and significance among select questions grouped into distinct themes, domains, and points of “maternal and newborn health–related knowledge” based on the priorities outlined in Nepal’s maternal and newborn health 2030 goals. Results: There was a significant improvement in knowledge scores on maternal and newborn health issues after watching the educational films for both types of participants. The mean knowledge score for pregnant women improved from 10 to 15 (P < 0.001) for the Understanding Antenatal Care (ANC) film, 3 to 10 (P < 0.001) for the Warning Sign in Pregnancy film, and 6 to 14 (P < 0.001) for the Newborn Care film. For the Female Community Health Volunteers, knowledge also significantly improved (P < 0.05) in all except one category after watching the postpartum hemorrhage film. The percent that correctly answered when to administer misoprostol (80%−95%) was the only variable in which knowledge improvement was not significant (P < 0.057). Conclusion: Using culturally adapted educational films is an effective intervention to improve short-term maternal and newborn health–related knowledge among rural populations with low educational levels. The authors recommend additional larger-scale trials of this type of intervention in Nepal and other low- and middle-income countries to determine the impact on long-term maternal and newborn health knowledge and behaviors among rural populations.
Impact of DNA Prime/Protein Boost Vaccination against Campylobacter jejuni on Immune Responses and Gut Microbiota in Chickens

Campylobacteriosis is reported to be the leading zoonosis in Europe, and poultry is the main reservoir of Campylobacter. Despite all the efforts made, there is still no efficient vaccine to fight this bacterium directly in poultry. Recent studies have reported interactions between the chicken immune system and gut microbiota in response to Campylobacter colonisation. The present study was designed to analyse in more depth the immune responses and caecal microbiota following vaccination with a DNA prime/protein boost flagellin-based vaccine that induces some protection in specific-pathogen-free White Leghorn chickens, as shown previously. These data may help to improve future vaccination protocols against Campylobacter in poultry. Here a vaccinated and a placebo group were challenged by C. jejuni at the age of 19 days. A partial reduction in Campylobacter loads was observed in the vaccinated group. This was accompanied by the production of specific systemic and mucosal antibodies. Transient relatively higher levels of Interleukin-10 and antimicrobial peptide avian β-defensin 10 gene expressions were observed in the vaccinated and placebo groups respectively. The analysis of caecal microbiota revealed the vaccination’s impact on its structure and composition. Specifically, levels of operational taxonomic units classified as Ruminococcaceae and Bacillaceae increased on day 40.
A fine balance of hydrophobic-electrostatic communication pathways in a pH-switching protein

Significance Accurately capturing the intricate interaction networks that control protein allostery is a central goal in protein science. We present a means to determine these networks by high-resolution NMR difference and coupling measurements, illustrated for pH-dependent myristoyl switching in hisactophilin. Integrated temperature and pH dependence of protein amide NMR synergistic with molecular dynamics (MD) simulations resolves nuances of a proteinwide interaction network, with proton binding by histidines in balance with extensive core and surface hydrophobic interactions. Analysis of mutant proteins demonstrates how this web of switching interactions can be broken, restored, and tuned. Thus, high-sensitivity NMR may be used to define the intricacies of interaction networks in a wide variety of protein and peptide systems.
An embodied approach to disability sport : the lived experience of visually impaired cricket players

This thesis investigates the England Visually Impaired Cricket Team, whose squad members comprise sixteen men aged 18-54, and their lived experiences' of playing visually impaired cricket. This is the first piece of research to examine elite visually impaired cricket and the first to explicitly analyse the social dynamics of any visually impaired sports team. Through an embodied theoretical approach, that accounts for the corporeal experience of impairment alongside the role of social institutions and discourse in the high performance culture of modern disability sport, this thesis establishes the significant aspects of this previously unexamined research 'site', both on and off the pitch. This study consisted of ten months of ethnographic fieldwork using participant observation and semi-structured interviews shaped by a new method of recording and eliciting data. To capture the participants' sensorial experiences of playing visually impaired cricket, 'soundscape elicitation', the process of composing auditory 'tracks' of the players' participation and then using these recordings during semi-structured interviews to prompt sensorial discussions, was utilised. This original and innovative method was central to the production of previously unexamined knowledge and is a significant methodological advancement in the wider field of sensory studies. The findings present a number of original contributions to knowledge regarding 'sporting bodies', the sensorial experiences of sport, and the construction of identity through disability sport. The participants' embodied experiences of playing visually impaired cricket reveal an alternative way of 'being' in sport and physical activity. However, it is the inescapable ocularcentric value of 'sight' that inhibits the resistive potential of the game. Instead of the presumed empowering experience, elite visually impaired cricket is disempowering for many participants due to the irreversible relationship of blind cricket institutions with mainstream cricketing bodies. Furthermore, a 'hierarchy of sight' based upon the official sight classification process emerges that highly values those players with the highest sight classifications and marginalises the blind players. All of these factors inform visually impaired cricket players’ construction of their own identities. Although many players view visually impaired cricket as a way of demonstrating their 'normality', it actually accentuates the impairment that they are attempting to dissociate from and is one of the few social situations where they are 'outed' as disabled or blind.
Verbreitung des betrieblichen Eingliederungsmanagements: Sind Gesundheitsorientierung und soziale Ressourcen bedeutsamer als Betriebsgröße? Ergebnisse der BIBB/BAuA-Erwerbstätigenbefragung 2018

Zusammenfassung Ziele und Methoden Auf Grundlage der repräsentativen BIBB/BAuA-Erwerbstätigenbefragung 2018 wird analysiert, ob die Verbreitung des betrieblichen Eingliederungsmanagements (BEM) mit ausgewählten strukturellen Merkmalen von Betrieben sowie Variablen aus dem Bereich sozialer Ressourcen zusammenhängt. Ein Zusammenhang mit Merkmalen, die auf eine betriebliche Priorisierung von Gesundheit und Sozialem hinweisen, wird angenommen. Zusätzlich werden die gleichen Variablen in Bezug auf die Inanspruchnahme von BEM betrachtet, ergänzt um personenbezogene Merkmale. Ergebnisse Rund vierzig Prozent der langzeiterkrankten Beschäftigten bekamen ein BEM angeboten, wovon fast siebzig Prozent das Angebot angenommen haben. BEM wurde eher in Betrieben angeboten, in denen Beschäftigten Maßnahmen der betrieblichen Gesundheitsförderung (BGF) bekannt waren, in denen häufig Lob und Anerkennung durch Vorgesetzte erfolgte, in denen sich häufig ein Gemeinschaftsgefühl am Arbeitsplatz fand und ein Betriebs- oder Personalrat vorhanden war. In kleineren Betrieben sowie in Dienstleistungs- und Handwerksbetrieben wurde das BEM-Angebot häufiger angenommen als in größeren Betrieben, im öffentlichen Dienst und in Betrieben der Industrie. Von den personenbezogenen Merkmalen wies nur eine längere Arbeitsunfähigkeit einen Zusammenhang mit der Inanspruchnahme auf. Schlussfolgerungen Die Zusammenhänge mit BGF und wertschätzendem Vorgesetztenverhalten legen den Schluss nahe, dass Betriebe, in denen gute und gesundheitsförderliche Arbeit einen höheren Stellenwert hat, eher die gesetzlichen Anforderungen zum BEM umsetzen. Gleichzeitig wäre es auch denkbar, dass ein umgekehrter Effekt vorliegt, und Betriebe die Einführung eines BEM aufgrund aufgetretener Fälle zum Anlass der Überprüfung ihres sonstigen Engagements für die Gesundheit der Beschäftigten genommen haben.
Artificial intelligence in pharmacovigilance: Do we need explainability?

With increasing deployment of complex and opaque machine learning algorithms (black boxes) to make decisions in areas that profoundly affect individuals such as underwriting, judicial sentencing, and robotic driving, are increasing calls for explanations of how they make these decisions to assure that they are accurate, objective, and fair. Black boxes are also being increasingly explored and deployed in real world pharmacovigilance, so an understandable question is whether such explainability is important in this domain as well. "Explainable artificial intelligence (AI)" refers to a set of tools that aim to provide understandable approximations, hypothesis, or more precise traces of the "inner thoughts" of black boxes. We consider whether and how general arguments made for explainable AI, such as building trust and gaining scientific insights, apply to pharmacovigilance including an explication of the limitations in these arguments and the methods themselves. Given the multiple application domains within pharmacovigilance, the answer to the question is situation dependent. If the field of explainable AI advances to the point of consistently providing high quality explanations as testable hypothesis, explainable artificial intelligence should be a credible addition to the pharmacovigilance toolkit for model development, signal management and clinical pharmacovigilance. Its incremental contribution to broad trust building per se, though widely touted in general, is a dubious argument for pharmacovigilance. This article is protected by copyright. All rights reserved.
Long-range chromosomal interactions increase and mark repressed gene expression during adipogenesis

ABSTRACT Obesity perturbs central functions of human adipose tissue, centred on differentiation of preadipocytes to adipocytes, i.e., adipogenesis. The large environmental component of obesity makes it important to elucidate epigenetic regulatory factors impacting adipogenesis. Promoter Capture Hi-C (pCHi-C) has been used to identify chromosomal interactions between promoters and associated regulatory elements. However, long range interactions (LRIs) greater than 1 Mb are often filtered out of pCHi-C datasets, due to technical challenges and their low prevalence. To elucidate the unknown role of LRIs in adipogenesis, we investigated preadipocyte differentiation to adipocytes using pCHi-C and bulk and single nucleus RNA-seq data. We first show that LRIs are reproducible between biological replicates, and they increase >2-fold in frequency across adipogenesis. We further demonstrate that genomic loci containing LRIs are more epigenetically repressed than regions without LRIs, corresponding to lower gene expression in the LRI regions. Accordingly, as preadipocytes differentiate into adipocytes, LRI regions are more likely to contain repressed preadipocyte marker genes; whereas these same LRI regions are depleted of actively expressed adipocyte marker genes. Finally, we show that LRIs can be used to restrict multiple testing of the long-range cis-eQTL analysis to identify variants that regulate genes via LRIs. We exemplify this by identifying a putative long range cis regulatory mechanism at the LYPLAL1/TGFB2 obesity locus. In summary, we identify LRIs that mark repressed regions of the genome, and these interactions increase across adipogenesis, pinpointing developmental regions that need to be repressed in a cell-type specific way for adipogenesis to proceed.
Every cubic Boolean function in 8 variables is the sum of not more than 4 bent functions

Boolean functions with extremal nonlinear properties are called bent functions. They are exactly those functions that have the maximal possible Hamming distance to the class of all affine Boolean functions in n variables. Note that degree of a bent function is not more than n/2. One of the most important problem in bent functions is to find the number of them. In [1] we introduced a new approach to this problem and formulated the following hypothesis: any Boolean function in n variables of degree not more than n/2 can be represented as the sum of two bent functions in n variables (n is even, n > 2). In general, it is interesting to obtain decompositions in constant number of bent functions. In this paper we study bent decompositions for Boolean functions in 8 variables. Recall that Boolean functions f and g in n variables are affine equivalent, if there exist nonsingular binary n × n matrix A, vectors u, v of length n and constant λ ∈ Z2, such that g(x) = = f(Ax+u)+〈v, x〉+λ, where 〈v, x〉 = x1v1+. +xnvn is the inner product. We study bent decompositions only for affine nonequivalent Boolean functions due to the following facts: • A Boolean function affine equivalent to a bent function is bent too. • Let a Boolean function f in n variables be represented as the sum of k bent functions. Then every Boolean function affine equivalent to f also can be represented as the sum of k bent functions. In [2] it is proven that every quadratic Boolean function in n variables (n is even) is the sum of two bent functions in n variables. The proof of this fact was based on the known affine classification of all quadratic Boolean functions in n variables (due to the Dickson’s theorem). Thus, let us consider Boolean functions of degree 3.
Tau-aggregation inhibition: promising role of nanoencapsulated dietary molecules in the management of Alzheimer’s disease

Abstract Alzheimer’s disease (AD) is a cumulative form of dementia associated with memory loss, cognition impairment, and finally leading to death. AD is characterized by abnormal deposits of extracellular beta-amyloid and intracellular Tau-protein tangles throughout the brain. During pathological conditions of AD, Tau protein undergoes various modifications and aggregates over time. A number of clinical trials on patients with AD symptoms have indicated the effectiveness of Tau-based therapies over anti-Aβ treatments. Thus, there is a huge paradigm shift toward Tau aggregation inhibitors. Several bioactives of plants and microbes have been suggested to cross the neuronal cell membrane and play a crucial role in managing neurodegenerative disorders. Bioactives mainly act as active modulators of AD pathology besides having antioxidant and anti-inflammatory potential. Studies also demonstrated the potential role of dietary molecules in inhibiting the formation of Tau aggregates and removing toxic Tau. Further, these molecules in nonencapsulated form exert enhanced Tau aggregation inhibition activity both in in vitro and in vivo studies suggesting a remarkable role of nanoencapsulation in AD management. The present article aims to review and discuss the structure-function relationship of Tau protein, the post-translational modifications that aid Tau aggregation and potential bioactives that inhibit Tau aggregation.
The challenges in diagnosing pediatric primary antiphospholipid syndrome

Pediatric primary antiphospholipid syndrome (APS) is a very rare disease with significant distinctions from the APS in adults. Herein, we present our experience in the diagnosis and treatment of six pediatric primary APS patients, who met the updated Sapporo criteria for the APS diagnosis. One of them was also diagnosed as having probable catastrophic APS (CAPS) due to the involvement of three different organ systems simultaneously. Besides vascular involvement, four patients had thrombocytopenia, one had psychiatric disorder, and one had chorea and valvular heart disease. All patients received immunosuppressive treatment along with long-term anticoagulation therapy. Specific neurologic and hematologic manifestations that are not part of the classification criteria can be seen in children with primary APS. Therefore, using the adult criteria for diagnosing pediatric APS may result in missed or delayed diagnoses in children.
Aortic valve calcification predicts poor outcomes after primary percutaneous coronary intervention

Aortic valve calcification (AVC) is associated with increased cardiovascular risk in the general population. We sought to investigate whether AVC identified by transthoracic echocardiography could be a predictor of long‐term adverse events after primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction.