Miracle-dz/UniFAR-FTUs huggingface dataset:
Chromatin epigenetics and nuclear lamina keep the nucleus in shape: Examples from natural and accelerated aging

As the repository of genetic information, the cell nucleus must protect DNA integrity from mechanical stresses. The nuclear lamina, which resides within the nuclear envelope (NE), is made up of lamins, intermediate filaments bound to DNA. The nuclear lamina provides the nucleus with the ability to deal with inward as well as outward mechanical stimuli. Chromatin, in turn, through its degrees of compaction, shares this role with the nuclear lamina, thus, ensuring the plasticity of the nucleus. Perturbation of chromatin condensation or the nuclear lamina has been linked to a plethora of biological conditions, that range from cancer and genetic diseases (laminopathies) to aging, both natural and accelerated, such as the case of Hutchinson‐Gilford Progeria Syndrome (HGPS). From the experimental results accumulated so far on the topic, a direct link between variations of the epigenetic pattern and nuclear lamina structure would be suggested, however, it has never been clarified thoroughly. This relationship, instead, has a downstream important implication on nucleus shape, genome preservation, force sensing, and, ultimately, aging‐related disease onset. With this review, we aim to collect recent studies on the importance of both nuclear lamina components and chromatin status in nuclear mechanics. We also aim to bring to light evidence of the link between DNA methylation and nuclear lamina in natural and accelerated aging.
Field-based assessment of the design of lysimeters for landfill final cover seepage control

ABSTRACT Lysimeters are considered the most appropriate instrument for assessing percolations rates through landfill final covers. Their design, however, must take into consideration the unsaturated nature of water seepage, otherwise they may act as a sink or cause flow avoidance. The aim of this study was to investigate whether using a simple approach to lysimeter design produces reliable seepage control data. Two different design methods were compared using a three-year field database of suction and seepage data collected from large-scale lysimeters installed at the St-Nicephore landfill in Canada. The first, or control, whose side walls were as high as the thickness of the cover material, was inspired from lysimeters installed during the Alternative Cover Assessment Program (ACAP; USA). The second lysimeter was designed based on the proposed simple design methodology, which focuses on the unsaturated flow and hydraulic properties of the materials to determine the optimal wall height. Analysis of the database did not show any indication of significant preferential flow, or alteration of the flow regime by the second lysimeter, which collected as much percolation as the control one (less than 5% difference). The linear method has not been tested for extreme climatic conditions and the wall heights calculated using this method may be very high when designed for very fine-grained soil covers.
Conditional Deletion of HIF‐2α in Mouse Nucleus Pulposus Reduces Fibrosis and Provides Mild and Transient Protection From Age‐Dependent Structural Changes in Intervertebral Disc

Hypoxia‐inducible factors (HIFs) are critical to the development and homeostasis of hypoxic tissues. Although HIF‐2α, one of the main HIF‐α isoforms, is expressed in nucleus pulposus (NP) cells, its functions remain unknown. We deleted HIF‐2α in the NP tissue using a notochord‐specific FoxA2Cre allele to study HIF‐2α function in the adult intervertebral disc. Unlike observations in HIF‐1αcKO mice, fate mapping studies using Rosa26‐mTmG reporter showed that HIF‐2α loss in NP did not negatively impact cell survival or affect compartment development. Rather, loss of HIF‐2α resulted in slightly better attributes of NP morphology in 14‐month‐old HIF‐2αcKO mice as evident from lower scores of degeneration. These 14‐month‐old HIF‐2αcKO mice also exhibited significant reduction in NP tissue fibrosis and lower collagen turnover in the annulus fibrosis (AF) compartment. Imaging‐Fourier transform‐infrared (FTIR) analyses showed decreased collagen and protein content in the NP and maintained chondroitin sulfate levels in 14‐month‐old HIF‐2αcKO. Mechanistically, global transcriptomic analysis showed enrichment of differentially expressed genes with Gene Ontology (GO) terms related to metabolic processes and cell development, molecular functions concerned with histone and protein binding, and associated pathways, including oxidative stress. Noteworthy, these morphological differences were not apparent in 24‐month‐old HIF‐2αcKO, indicating that aging is the dominant factor in governing disc health. Together these data suggest that loss of HIF‐2α in the NP compartment is not detrimental to the intervertebral disc development but rather mitigates NP tissue fibrosis and offers mild but transient protection from age‐dependent early degenerative changes. © 2022 American Society for Bone and Mineral Research (ASBMR).
Lived Experience of Breast Cancer Survivors: A Phenomenological Study

ABSTRACT Background Breast cancer (BrCa) is the most common cancer worldwide. Five-year survival rates among individuals with BrCa are the highest of all types of cancer, yet there is a paucity of knowledge about the experiences of survivors regarding living through their diagnosis and treatment. In-depth interviews and the systematic analysis of self-reported experiences may provide in-depth information about the BrCa survivorship experience. Purpose This qualitative study was designed to identify and elucidate the lived experiences of Thai women with BrCa who successfully completed their treatment program for BrCa and/or treatment with chemotherapy for over 5 years and are currently cancer-free. Methods A phenomenological method was employed. Survivors of BrCa who met the inclusion criteria were purposively selected and invited to take part in the study. Study data were collected between January and March 2019. An open-ended, in-depth interview guide was used to direct the conversation concerning the participants' experiences and perceptions. Thematic analysis was used for data analysis. Results Data saturation was reached after 12 interviews. The five themes derived from the data include (a) being distressed, (b) accepting treatments and seeking alternative treatments, (c) going through difficult times, (d) becoming a stronger person, and (e) becoming thankful. Conclusions/Implications for Practice The experiences and themes identified enhance scholarly understanding regarding the experience of survivors of BrCa. A true understanding of this experience enables healthcare providers to craft and deliver appropriate interventions that provide quality care and improve women's health, thereby enhancing their quality of life. The results of this study may contribute to the development of new theories by using different qualitative approaches such as grounded theory.
Intestinal epithelial c-Maf expression determines enterocyte differentiation and nutrient uptake in mice

This study identifies c-Maf as an enterocyte-specific transcription factor within the small intestinal epithelium. c-Maf governs the spatial and functional specialization of enterocytes, especially gene programs controlling intestinal nutrient absorption. Thus, epithelial c-Maf deletion results in impaired enterocyte maturation, nutrient uptake, and alterations of the immune system and microbiota.
Electromagnetic Processes at High Energies in Oriented Single Crystals

A Theory of Radiation and Pair Creation in External Field The Quasiclassical Method of Describing the Radiation of High-Energy Particles Pair Production by a Photon in an External Field Radiation of Particles Moving Quasiperiodically and in a Superpositon of a Plane Wave and a Constant Field Fast Particles Penetration in Single Crystals Pair Production in Aligned Single Crystal Emission of Radiation by High-Energy Particles in Oriented Single Crystals Electromagnetic Radiation of Particles in Channelling Some Further Problems of the Theory of Electromagnetic Processes in Aligned Single Crystals. (Part contents).
Cortical thickness and its relationship to cognitive performance and metabolic control in adults with phenylketonuria

Despite good control of phenylalanine (Phe) levels during childhood and adolescence, adults with phenylketonuria (PKU) often show abnormalities in the white matter of the brain, which have been associated with poorer cognitive performance. However, whether such a relationship exists with cortical gray matter is still unknown. Therefore, we investigated cortical thickness and surface area in adults with early‐treated PKU and their relationship to cognitive functions and metabolic control. We included 30 adult patients with early‐treated and metabolically well‐controlled PKU (median age: 35.5 years) and 54 healthy controls (median age: 29.3 years). Surface‐based morphometry was derived from T1‐weighted magnetic resonance images using FreeSurfer, and general intelligence, executive functions, and attention were assessed. Concurrent plasma Phe, tyrosine, and tryptophan levels were measured in patients. In addition, Phe levels were collected retrospectively to calculate the index of dietary control. Patients showed a thinner cortex than controls in regions of the bilateral temporal, parietal, and occipital lobes (effect size r = −0.34 to −0.42, p < 0.05). No group differences in surface area were found. In patients, accuracy in the working memory task was positively correlated with thickness in the left insula (r = 0.45, p = 0.013), left fusiform gyrus (r = 0.39, p = 0.032), and right superior temporal gyrus (r = 0.41, p = 0.024), but did not survive false discovery rate correction. Neither concurrent nor historical metabolic parameters were related to cortical thickness. Taken together, adults with PKU showed widespread reductions in cortical thickness despite good metabolic control in childhood and adolescence. However, alterations in cortical thickness were unrelated to metabolic parameters and cognitive performance.
Metabolically Healthy Obesity: Epidemiology, Criteria, and Implications in Chronic Kidney Disease

The increasing prevalence of obesity is a worldwide health concern. Although obesity primarily affects the development of cardiometabolic disorders, it has also been closely linked to chronic kidney disease (CKD). However, potential causal relationships between obesity and CKD remain unclear, as obesity and CKD share a number of common risk factors. Accordingly, the risk of incident CKD in obese people without metabolic abnormalities, also called “metabolically healthy obesity” (MHO), has been a matter of interest. Recent investigations found that MHO was related to increased risk of incident CKD; however, the conclusions were based primarily on the static state. According to previous publications, approximately one-half of people initially identified as MHO became metabolically unhealthy, while one-tenth reduced their body weight to normal range while remaining metabolically healthy. It is essential to consider these transitions in obese-metabolic health status when analyzing obesity-related outcomes. This review discusses research on obesity and metabolic health in patients with CKD. Furthermore, we summarize recent reports on the implications of obesity and metabolic health in CKD and discuss the possible mechanisms of their relationship with CKD.
Chimeric DNA byproducts in strand displacement amplification using the T7 replisome

Recent advances in next generation sequencing technologies enable reading DNA molecules hundreds of kilobases in length and motivate development of DNA amplification methods capable of producing long amplicons. In vivo, DNA replication is performed not by a single polymerase enzyme, but multiprotein complexes called replisomes. Here, we investigate strand-displacement amplification reactions using the T7 replisome, a macromolecular complex of a helicase, a single-stranded DNA binding protein, and a DNA polymerase. The T7 replisome may initiate processive DNA synthesis from DNA nicks, and the reaction of a 48 kilobase linear double stranded DNA substrate with the T7 replisome and nicking endonucleases is shown to produce discrete DNA amplicons. To gain a mechanistic understanding of this reaction, we utilized Oxford Nanopore long-read sequencing technology. Sequence analysis of the amplicons revealed chimeric DNA reads and uncovered a connection between template switching and polymerase exonuclease activity. Nanopore sequencing provides insight to guide the further development of isothermal amplification methods for long DNA, and our results highlight the need for high-specificity, high-turnover nicking endonucleases to initiate DNA amplification without thermal denaturation.
Most common principal diagnoses assigned to Australian emergency department presentations involving alcohol use: a multi‐centre study

Objectives: Alcohol is the most widely consumed psychoactive substance in Australia and the consequences of alcohol consumption have enormous personal and social impacts. This study aimed to describe the principal diagnoses of emergency department (ED) presentations involving alcohol use in the previous 12 hours at eight hospitals in Victoria and the Australian Capital Territory, Australia.
Systematic review and meta‐analysis on the association between theory of mind and alcohol problems in non‐clinical samples

Abstract Background Deficits in theory of mind (ToM) found in individuals with alcohol use disorder (AUD) are often thought to result from prolonged heavy alcohol use. However, links between deficits in ToM and greater alcohol problems are often also present in non‐clinical samples (e.g., adolescents and young adults) who may not have a similar long‐lasting history of alcohol consumption as individuals with AUD. The current study is the first to systematically review and meta‐analyze results from studies examining associations between lower ToM and greater alcohol problems in non‐clinical samples. Evidence of reliable associations in these non‐clinical samples would support the idea that deficits in ToM might also precede the emergence of AUD. Methods PsycINFO, PubMed, and Google Scholar were searched according to our preregistered International Prospective Register of Systematic Reviews (PROSPERO) protocol (CRD42021225392) and following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) methodology. We systematically reviewed sample characteristics and ToM measures in identified articles. We then meta‐analyzed the findings of association between ToM and alcohol problems in non‐clinical samples using random effects models. Results Nearly all studies used a measure of ToM that assessed the ability to infer the mental states of others based on eye region cues. Meta‐analytic results demonstrated that lower ToM was associated with more alcohol problems (r = −0.16, k = 6, CI = [−0.26, −0.04], p < 0.01, Q = 15.55, I 2 = 67.85), and there was significant heterogeneity across studies. Gender (ß = 0.0003, CI = [−0.006, 0.007], z = 0.09, p = 0.93), age (ß = −0.008, CI = [−0.03, 0.01], z = −0.82, p = 0.42), and study quality (ß = −0.10, CI = [−0.35, 0.15], z = −0.82, p = 0.41) did not explain the heterogeneity. Conclusion In non‐clinical samples, lower ToM is associated with more alcohol problems, indicative of a small effect size. Future longitudinal studies are needed to explore whether socio‐cognitive deficits may also serve as a risk factor for alcohol misuse.
Effect of socioeconomic status on smoking cessation behavior in selected African countries: Secondary analysis of Global Adult Tobacco Survey data (2014–2018)

Introduction Tobacco use remains a global public health challenge. While studies report that smoking cessation reduces the risk of cancer and other NCDs, evidence is scarce in African region on socio-economic determinants of smoking cessation behavior. This study examined the socio-economic differentials of smoking cessation behavior among smokers in four African countries. Methods The study was conducted through secondary analysis of Global Adult Tobacco Survey (GATS) data from four African countries (Ethiopia, Kenya, Senegal and Tanzania). Smoking cessation behavior was assessed using two variables i) intention to quit smoking in next 12 months and ii) previous quit attempts made within 12 months preceding the survey. The weighted percentages for intention to quit smoking and previous quit attempts were computed. The adjusted odds ratios were computed using multinomial logistic regression to identify the association between socio-economic factors and smoking cessation behavior. Results Across the four countries studied, the previous quit attempts among smokers were in the range of 39.6% to 53.7%. Around 7.6% to 15.8% of the smokers tried to quit with an assistance. In Ethiopia over 76.5% of current smokers reported no intention to quit in next 12 months after survey, whereas the same was 50.4% in Senegal. While country specific differences were observed, females, those belonging to the poorest wealth index, unemployed and those without any formal education reported significantly lower odds of previous quit attempts or having an intention to quit smoking. Conclusion The socio-economic vulnerabilities were found to compromise smoking cessation behavior among the smokers in countries studied. Targeted interventions, adherence to smokefree laws, and provision of cessation support are essential to improve quit rates and mitigate tobacco risks among socio-economically vulnerable population.
Impact of inter‐hospital transfer on success of angioembolization for lower gastrointestinal bleeding

Angioembolization is a useful therapeutic tool for lower gastrointestinal bleeding (LGIB) however is only available at centres with specialist interventional radiology departments. Delay in angioembolization of greater than 120–150 minutes is associated with higher rates of non‐therapeutic angioembolization.
Maternal fructose intake during pregnancy and lactation: Later effects on renal function

Excessive fructose consumption has been associated with hypertension and metabolic disorders and can alter physiological adaptations during pregnancy, with long‐term detrimental consequences. This study evaluated in post‐weaning mothers the effects of increased fructose consumption during pregnancy and lactation on blood pressure and renal function. Female Wistar rats were assigned to one of four experimental groups: non‐pregnant control (NPC); pregnant control (PC); non‐pregnant fructose (NPF), and pregnant fructose (PF). Control rats had free access to food and water, while the fructose groups had free access to food and to a 20% fructose solution, over the time period of the experiment. The systolic BP and renal function parameters were measured at the end of the experimental period, one week after weaning (28 days after delivery). The results were presented as means ± standard error. Higher values of BP were observed in both pregnant and non‐pregnant rats treated with fructose compared to control. Creatinine clearance was reduced only in the PF group; however, both the PF and NPF groups had reduced Na+ and K+ excretions. In the PF group, there was also glomerular enlargement and changes in the media/lumen (M/L) ratio of interlobular arteries. Additionally, the PF group showed increased macrophage infiltration and expression of alpha‐SM‐actin and reduced expression of nitric‐oxide‐synthase endothelial in renal tissue. These findings suggest that the association of high fructose intake with pregnancy aggravated kidney changes that persisted for up to four weeks after delivery, which may represent a risk factor for maternal health.
Minimal injective resolutions and Auslander-Gorenstein property for path algebras

ABSTRACT Let R be a ring and 𝒬 be a finite and acyclic quiver. We present an explicit formula for the injective envelopes and projective precovers in the category Rep(𝒬,R) of representations of 𝒬 by left R-modules. We also extend our formula to all terms of the minimal injective resolution of R𝒬. Using such descriptions, we study the Auslander-Gorenstein property of path algebras. In particular, we prove that the path algebra R𝒬 is k-Gorenstein if and only if and R is a k-Gorenstein ring, where n is the number of vertices of 𝒬.
Retention of basic surgical skills in veterinary students.

OBJECTIVE To quantify veterinary students' retention of surgical skills after a 5-month period without practice. STUDY DESIGN Prospective longitudinal descriptive study. SAMPLE POPULATION Convenience sample of second year veterinary students (n = 57). METHODS Students practiced ovariohysterectomy (OVH) on a model during 4 clinical skills laboratories during spring 2021. Students were assessed performing OVH on their model using a validated 22-item rubric. Students not meeting expectations repeated their assessment 2 weeks later. All students had a 5-month period, including summer break, without skills practice. Students were again assessed performing OVH on their model in the fall. Students' rubric scores and pass rates were compared before and after summer break. RESULTS Students scored lower on their retention test in fall (median = 43) than at the spring assessment (median = 56, P < .001). No difference was detected between lower and higher performing students. Five students (9%) did not meet expectations on their first assessment; more students (17/57, 30%) failed to meet expectations on their retention test (P = .004). CONCLUSION Students experienced a decay in the surgical skills required to perform OVH after a 5-month period without practice, regardless of the quality of their initial performance. CLINICAL SIGNIFICANCE Veterinary educators should emphasize the importance of continual practice to maintain skills and should consider assisting students in regaining skills during review sessions on models to improve surgical skill retention after a prolonged break.
Gut Microbiome–Wide Search for Bacterial Azoreductases Reveals Potentially Uncharacterized Azoreductases Encoded in the Human Gut Microbiome

The human gut is home to trillions of microorganisms that are responsible for the modification of many orally administered drugs, leading to a wide range of therapeutic outcomes. Prodrugs bearing an azo bond are designed to treat inflammatory bowel disease and colorectal cancer via microbial azo reduction, allowing for topical application of therapeutic moieties to the diseased tissue in the intestines. Despite the inextricable link between microbial azo reduction and the efficacy of azo prodrugs, the prevalence, abundance, and distribution of azoreductases have not been systematically examined across the gut microbiome. Here, we curated and clustered amino acid sequences of experimentally confirmed bacterial azoreductases and conducted a hidden Markov model–driven homolog search for these enzymes across 4644 genome sequences present in the representative Unified Human Gastrointestinal Genomes collection. We identified 1958 putative azo-reducing species, corroborating previous findings that azo reduction appears to be a ubiquitous function of the gut microbiome. However, through a systematic comparison of predicted and confirmed azo-reducing strains, we hypothesize the presence of uncharacterized azoreductases in 25 prominent strains of the human gut microbiome. Finally, we confirmed the azo reduction of Acid Orange 7 by multiple strains of Fusobacterium nucleatum, Bacteroides fragilis, and Clostridium clostridioforme. Together, these results suggest the presence and activity of many uncharacterized azoreductases in the human gut microbiome and motivate future studies aimed at characterizing azoreductase genes in prominent members of the human gut microbiome. SIGNIFICANCE STATEMENT This work systematically examined the prevalence, abundance, and distribution of azoreductases across the healthy and inflammatory bowel disease human gut microbiome, revealing potentially uncharacterized azoreductase genes. It also confirmed the reduction of Acid Orange 7 by strains of Fusobacterium nucleatum, Bacteroides fragilis, and Clostridium clostridioforme.