Miracle-dz/UniFAR-FTUs huggingface dataset:
Experimental and Bioinformatic Approaches to Studying DNA Methylation in Cancer

Simple Summary Aberrations of normal DNA methylation patterns are observed in many cancers and are associated with chromatin alterations, changes in gene expression and genomic instability, making the study of DNA methylation paramount to our understanding of cancer biology and evolution and the development of biomarkers. Here, we present an overview of genome-wide approaches for the analysis of DNA methylation with relevance to cancer research and clinics. Abstract DNA methylation is an essential epigenetic mark. Alterations of normal DNA methylation are a defining feature of cancer. Here, we review experimental and bioinformatic approaches to showcase the breadth and depth of information that this epigenetic mark provides for cancer research. First, we describe classical approaches for interrogating bulk DNA from cell populations as well as more recently developed approaches for single cells and multi-Omics. Second, we focus on the computational analysis from primary data processing to the identification of unique methylation signatures. Additionally, we discuss challenges such as sparse data and cellular heterogeneity.
Role of Fibroblasts and Myofibroblasts on the Pathogenesis and Treatment of Pelvic Organ Prolapse

Pelvic organ prolapse (POP) is a multifactorial connective tissue disorder caused by damage to the supportive structures of the pelvic floor, leading to the descent of pelvic organs in the vagina. In women with POP, fibroblast function is disturbed or altered, which causes impaired collagen metabolism that affects the mechanical properties of the tissue. Ideal surgical repair, either native tissue repair or POP surgery using an implant, aims to create a functional pelvic floor that is load-bearing, activating fibroblasts to regulate collagen metabolism without creating fibrotic tissue. Fibroblast function plays a crucial role in the pathophysiology of POP by directly affecting the connective tissue quality. On the other hand, fibroblasts determine the success of the POP treatment, as the fibroblast-to-(myo)fibroblast transition is the key event during wound healing and tissue repair. In this review, we aim to resolve the question of “cause and result” for the fibroblasts in the development and treatment of POP. This review may contribute to preventing the development and progress of anatomical abnormalities involved in POP and to optimizing surgical outcomes.
Burnout, Depression, and Anxiety Levels among Healthcare Workers Serving Children with Autism Spectrum Disorder

Burnout in healthcare workers (HCWs) is defined as a state of emotional, physical, and mental exhaustion that results from unmanaged, excessive, and long-term workplace stressors. This study aims to assess the prevalence of burnout and the levels of anxiety and depression among HCWs who primarily work with children who have autism spectrum disorder (ASD). A quantitative cross-sectional survey was conducted utilizing the Arabic version of the Maslach Burnout Inventory (MBI), Areas of Worklife Survey (AWS), Patient Health Questionnaire for Generalized Anxiety Disorder (GAD-7), and Patient Health Questionnaire for Depression (PHQ-9). Among the 381 participants working in autism centers, the majority were young Saudi females (326) working full-time as specialists in the private sector with less than five years of experience. The HCWs’ overall mean scores on the three Maslach Burnout Inventory (MBI) subscales: emotional exhaustion (EE), depersonalization (DP), and personal accomplishment (PA) were 62%, 23.7%, and 76.5%, respectively. A total of 51.4% of HCWs reported moderate to high anxiety levels on GAD-7, and 47.8% showed moderate to very high levels of depression on PHQ-9. The mean perceived EE converged significantly but negatively on their overall mean perceived satisfaction with AWS (p-value < 0.001), demonstrating that greater emotional fatigue predicts less satisfaction with their work. The PA scores correlated significantly and positively with their overall mean satisfaction with their AWS score (p-value < 0.001). Considering sociodemographic variables, HCWs aged between 20–29 years have significantly lower mean PA scores than HCWs aged thirty and older (p = 0.007). Also, male HCWs perceived significantly higher work-related DP than females. More research is required to determine the nature of variables that contribute to burnout, depression, and anxiety in HCWs helping children with ASD.
Effectiveness and safety assessment of orthopedic device (LSM-01) for low back pain

Abstract Background: More than 80% of the population suffer from low back pain at some time during their lives. An orthopedic device (LSM-01) will be used to alleviate back pain caused by muscle tension. LSM-01, which has a rotating roller, stimulates meridian-muscles around the governor vessel, bladder meridian, and gall bladder meridian. Methods: This study will be a randomized, single-blinded, sham-controlled, parallel-group, pilot clinical trial. Subjects will be randomly allocated to the treatment group (LSM-01) or the control group (sham device). The duration of the clinical trial will be 2 weeks. The primary outcomes will be measured using the visual analog scale; the secondary outcomes will include pressure pain threshold, Oswestry Disability Index, and Patient Global Impression of Change. Statistical analysis will be performed for the full study population. Analysis of covariance will be conducted to identify differences in pain before and after the application of the device. Discussion: This clinical trial will evaluate the safety and efficacy of the LSM-01 device. As a pilot study, this investigation includes a limited number of subjects. The results of this pilot trial will form a basis for a large-scale clinical trial, which will be conducted in the future. Clinical trial registration: This study protocol is registered with the Clinical Research Information Service (CRIS) of Korea. Clinical trial registration number: CRIS-KCT0006425. Registered: October 5, 2021; https://cris.nih. go.kr/cris/search/detailSearch.do? search_lang=E&search_page=L&pageSize=10&page=undefined&seq=20056&status=5&seq_group=20056
Weekend Mortality in an Italian Hospital: Immediate versus Delayed Bedside Critical Care Treatment

Background: a number of studies highlighted increased mortality associated with hospital admissions during weekends and holidays, the so–call “weekend effect”. In this retrospective study of mortality in an acute care public hospital in Italy between 2009 and 2015, we compared inpatient mortality before and after a major organizational change in 2012. The new model (Model 2) implied that the intensivist was available on call from outside the hospital during nighttime, weekends, and holidays. The previous model (Model 1) ensured the presence of the intensivist coordinating a Medical Emergency Team (MET) inside the hospital 24 h a day, 7 days a week. Methods: life status at discharge after 9298 and 8223 hospital admissions that occurred during two consecutive periods of 1185 days each (organizational Model 1 and 2), respectively, were classified into “discharged alive”, “deceased during nighttime–weekends–holidays” and “deceased during daytime-weekdays”. We estimated Relative Risk Ratios (RRR) for the associations between the organizational model and life status at discharge using multinomial logistic regression models adjusted for demographic and case-mix indicators, and timing of admission (nighttime–weekends–holidays vs. daytime-weekdays). Results: there were 802 and 840 deaths under Models 1 and 2, respectively. Total mortality was higher for hospital admissions under Model 2 compared to Model 1. Model 2 was associated with a significantly higher risk of death during nighttime–weekends–holidays (IRR: 1.38, 95% CI 1.20–1.59) compared to daytime–weekdays (RRR: 1.12, 95% CI 0.97–1.31) (p = 0.04). Respiratory diagnoses, in particular, acute and chronic respiratory failure (ICD 9 codes 510–519) were the leading causes of the mortality excess under Model 2. Conclusions: our data suggest that the immediate availability of an intensivist coordinating a MET 24 h, 7 days a week can result in a better prognosis of in-hospital emergencies compared to delayed consultation.
Median Nerve Affection in Hypertensive Patients with and without Diabetes High-Resolution Ultrasound Assessment

Purpose Diabetes is a documented risk factor for peripheral neuropathy. It was reported that associated hypertension could increase this risk. The present study aimed to assess the effect of hypertension and diabetes on median nerve using high-resolution ultrasound. Methods The study includes 50 hypertensive patients (HTN group), 50 diabetic patients (DM group), 50 patients with coexisting diabetes and hypertension (HTN + DM group) and 50 healthy controls. Median nerve affection in the studied groups was studied by vibration perception thresholds (VPT). The median nerve cross-sectional area was determined at the nerve cross-sectional area of the median nerve at the carpal tunnel by high-resolution ultrasound. Clinical symptoms were assessed using Toronto Clinical Severity Score (TCSS). Results There was significantly higher median nerve CSA in all patient groups in comparison to controls. HTN + DM group had significantly higher median nerve CSA when compared with DM group. Patients with peripheral neuropathy in HTN + DM and DM groups had significantly higher median nerve CSA than patients without. Using ROC curve analysis, it was shown that median CSA could successfully distinguish patients with peripheral neuropathy from patients without in HTN + DM group [AUC (95% CI): 0.71 (0.54–0.89)] and in DM group [AUC (95% CI): 0.86 (0.72–0.99)]. Conclusion Hypertensive patients with and without diabetes have significantly higher median nerve CSA when compared with controls.
Diffuse proliferative cerebral angiopathy: a case report and literature review on a very rare and misdiagnosed entity

Abstract Diffuse proliferative cerebral angiopathy (DPCA) is an uncommon type of cerebral vascular malformation, mostly diagnosed in young females. It is characteristically different from other cerebral arteriovenous malformations and can be differentiated by its peculiar imaging findings. A nidus of normal brain parenchyma is present between the abnormal vascular channels. Therefore, it is crucial to diagnose it as a separate entity because unnecessary treatment of DPCA increases the risk of damage to the normal parenchyma leading to neurological deficits. Here we describe a case of a 60-year-old male who presented with severe neurological deficits and was later diagnosed with DPCA. He was managed conservatively with antiepileptics and almost completely recovered to normal within 2 weeks. A rare case of DPCA confused with other hemorrhagic disorders is discussed here. Rare cases are often overlooked. Correct diagnosis helps to prevent tragic consequences.
Hyperthermic Intraperitoneal Chemotherapy in the Management of Gastric Cancer: A Narrative Review

Gastric cancer (GC) patients with peritoneal metastasis tend to achieve poor clinical outcomes. Until recently, the treatment options were limited mainly to either palliative chemotherapy or radiation therapy in exceptional cases. Currently, these patients benefit from multimodal treatment, such as cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Despite good overall results, this treatment modality is still widely debated. The following study is designed to assess the papers about the possible application and utility of HIPEC in GC. A search in the PubMed, Web of Science, and Scopus databases was performed to assess the papers devoted to the role of HIPEC in GC treatment; a literature search was performed until March 21st; and, finally, 50 studies with a total number of 3946 patients were analyzed. According to the most recent data, it seems to be reasonable to limit the duration of HIPEC to the shortest effective time. Moreover, the drugs used in HIPEC need to have equal concentrations and the same solvent. Perioperative chemotherapy needs to be reported in detail and, furthermore, the term “morbidity” should be defined more clearly by the authors.
The Quality Changes and Proteomic Analysis of Cattle Muscle Postmortem during Rigor Mortis

Rigor mortis occurs in a relatively early postmortem period and is a complex biochemical process in the conversion of muscle to meat. Understanding the quality changes and biomarkers during rigor mortis can provide a theoretical basis for maintaining and improving meat quality. Herein, a tandem mass tag proteomic method is used to investigate the effects of differentially expressed proteins on the meat quality of cattle Longissimus lumborum muscle postmortem (0, 6, and 24 h). The pH, total sulfhydryl content and sarcomere length decrease significantly during storage. In contrast, meat color values (L*, a*, and b*) and the myofibril fragmentation index increase significantly. Altogether, 147 differentially expressed proteins are identified, most being categorized as metabolic enzymes, mitochondrial proteins, necroptosis and ferroptosis proteins and structural proteins. The results also reveal additional proteins that are potentially involved in rigor mortis, such as cardiac phospholamban, acetyl-coenzyme A acyltransferase, and ankyrin repeat domain 2. The current results provide proteomic insights into the changes in meat quality during rigor mortis.
Probiotics counteract the expression of hepatic profibrotic genes via the attenuation of TGF-β/SMAD signaling and autophagy in hepatic stellate cells

Hepatic fibrosis is caused by the increased accumulation and improper degradation of extracellular matrix (ECM) proteins in the liver. Hepatic stellate cells (HSCs) activation is a key process in initiating hepatic fibrosis and can be ameliorated by the administration of probiotic strains. This study hypothesized that LAB strains (Lactiplantibacillus plantarum, Lactobacillus brevis, and Weissella cibaria) might attenuate pro-fibrogenic cytokine TGF-β mediated HSCs activation and induce collagen deposition, expression of other fibrogenic/inflammatory markers, autophagy, and apoptotic processes in vitro. Few studies have evaluated the probiotic effects against fibrogenesis in vitro. In this study, TGF-β exposure increased collagen deposition in LX-2 cells, but this increase was diminished when the cells were pretreated with LAB strains before TGF-β stimulation. TGF-β not only increased collagen deposition, but it also significantly upregulated the mRNA levels of Col1A1, alpha-smooth muscle actin (α-SMA), matrix metalloproteinases-2 (MMP-2), IL-6, CXCL-8, CCL2, and IL-1β in LX-2 cells. Pretreatment of the cells with LAB strains counteracted the TGF-β-induced pro-fibrogenic and inflammatory markers by modulating SMAD-dependent and SMAD-independent TGF-β signaling. In addition, LX-2 cells exposed to TGF-β induced the autophagic and apoptotic associated proteins that were also positively regulated by the LAB strains. These findings suggest that LAB can attenuate TGF-β signaling that is associated with liver fibrogenesis.
Forest Fire Detection via Feature Entropy Guided Neural Network

Forest fire detection from videos or images is vital to forest firefighting. Most deep learning based approaches rely on converging image loss, which ignores the content from different fire scenes. In fact, complex content of images always has higher entropy. From this perspective, we propose a novel feature entropy guided neural network for forest fire detection, which is used to balance the content complexity of different training samples. Specifically, a larger weight is given to the feature of the sample with a high entropy source when calculating the classification loss. In addition, we also propose a color attention neural network, which mainly consists of several repeated multiple-blocks of color-attention modules (MCM). Each MCM module can extract the color feature information of fire adequately. The experimental results show that the performance of our proposed method outperforms the state-of-the-art methods.
Synergetic Fermentation of Glucose and Glycerol for High-Yield N-Acetylglucosamine Production in Escherichia coli

N-acetylglucosamine (GlcNAc) is an amino sugar that has been widely used in the nutraceutical and pharmaceutical industries. Recently, microbial production of GlcNAc has been developed. One major challenge for efficient biosynthesis of GlcNAc is to achieve appropriate carbon flux distribution between growth and production. Here, a synergistic substrate co-utilization strategy was used to address this challenge. Specifically, glycerol was utilized to support cell growth and generate glutamine and acetyl-CoA, which are amino and acetyl donors, respectively, for GlcNAc biosynthesis, while glucose was retained for GlcNAc production. Thanks to deletion of the 6-phosphofructokinase (PfkA and PfkB) and glucose-6-phosphate dehydrogenase (ZWF) genes, the main glucose catabolism pathways of Escherichia coli were blocked. The resultant mutant showed a severe defect in glucose consumption. Then, the GlcNAc production module containing glucosamine-6-phosphate synthase (GlmS*), glucosamine-6-phosphate N-acetyltransferase (GNA1*) and GlcNAc-6-phosphate phosphatase (YqaB) expression cassettes was introduced into the mutant, to drive the carbon flux from glucose to GlcNAc. Furthermore, co-utilization of glucose and glycerol was achieved by overexpression of glycerol kinase (GlpK) gene. Using the optimized fermentation medium, the final strain produced GlcNAc with a high stoichiometric yield of 0.64 mol/mol glucose. This study offers a promising strategy to address the challenge of distributing carbon flux in GlcNAc production.
Crosstalk between Oxidative Stress and Inflammatory Liver Injury in the Pathogenesis of Alcoholic Liver Disease

Alcoholic liver disease (ALD) is characterized by the injury, inflammation, and scarring in the liver owing to excessive alcohol consumption. Currently, ALD is a leading cause for liver transplantation. Therefore, extensive studies (in vitro, in experimental ALD models and in humans) are needed to elucidate pathological features and pathogenic mechanisms underlying ALD. Notably, oxidative changes in the liver have been recognized as a signature trait of ALD. Progression of ALD is linked to the generation of highly reactive free radicals by reactions involving ethanol and its metabolites. Furthermore, hepatic oxidative stress promotes tissue injury and, in turn, stimulates inflammatory responses in the liver, forming a pathological loop that promotes the progression of ALD. Accordingly, accumulating further knowledge on the relationship between oxidative stress and inflammation may help establish a viable therapeutic approach for treating ALD.
Mechanism of Pterostilbene-Induced Cell Death in HT-29 Colon Cancer Cells

Pterostilbene is a dietary phytochemical that has been found to possess several biological activities, such as antioxidant and anti-inflammatory. Recent studies have shown that it exhibits the hallmark characteristics of an anticancer agent. The aim of the study was to investigate the anticancer activity of pterostilbene against HT-29 human colon cancer cells, focusing on its influence on cell growth, differentiation, and the ability of this stilbene to induce cell death. To clarify the mechanism of pterostilbene activity against colon cancer cells, changes in the expression of several genes and proteins that are directly related to cell proliferation, signal transduction pathways, apoptosis, and autophagy were also evaluated. Cell growth and proliferation of cells exposed to pterostilbene (5–100 µM) were determined by SRB and BRDU assays. Flow cytometric analyses were used for cell cycle progression. Further molecular investigations were performed using quantitative real-time RT-PCR. The expression of the signaling proteins studied was determined by the ELISA method. The results revealed that pterostilbene inhibited proliferation and induced the death of HT-29 colon cancer cells. Pterostilbene, depending on concentration, caused inhibition of proliferation, G1 cell arrest, and/or triggered apoptosis in HT-29 cells. These effects were mediated by the down-regulation of the STAT3 and AKT kinase pathways. It may be concluded that pterostilbene could be considered as a potential therapeutic option in the treatment of colon cancer in the future.
A Systematic Review of Orthosiphon stamineus Benth. in the Treatment of Diabetes and Its Complications

(1) Background: Orthosiphon stamineus Benth. is a traditional medicine used in the treatment of diabetes and chronic renal failure in southern China, Malaysia, and Thailand. Diabetes is a chronic metabolic disease and the number of diabetic patients in the world is increasing. This review aimed to systematically review the effects of O. stamineus in the treatment of diabetes and its complications and the pharmacodynamic material basis. (2) Methods: This systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), using the databases ScienceDirect, PubMed, and Web of Science. (3) Results: Thirty-one articles related to O. stamineus and diabetes were included. The mechanisms of O. stamineus in the treatment of diabetes and its complications mainly included inhibiting α-amylase and α-glucosidase activities, antioxidant and anti-inflammatory activities, regulating lipid metabolism, promoting insulin secretion, ameliorating insulin resistance, increasing glucose uptake, promoting glycolysis, inhibiting gluconeogenesis, promoting glucagon-likepeptide-1 (GLP-1) secretion and antiglycation activity. Phenolic acids, flavonoids and triterpenoids might be the main components for hypoglycemia effects in O. stamineus. (4) Conclusion: O. stamineus could be an antidiabetic agent to treat diabetes and its complications. However, it needs further study on a pharmacodynamic substance basis and the mechanisms of effective constituents.
Neurotoxic Potential of Deoxynivalenol in Murine Brain Cell Lines and Primary Hippocampal Cultures

Chronic exposure to the mycotoxin deoxynivalenol (DON) from grain-based food and feed affects human and animal health. Known consequences include entereopathogenic and immunotoxic defects; however, the neurotoxic potential of DON has only come into focus more recently due to the observation of behavioural disorders in exposed farm animals. DON can cross the blood-brain barrier and interfere with the homeostasis/functioning of the nervous system, but the underlying mechanisms of action remain elusive. Here, we have investigated the impact of DON on mouse astrocyte and microglia cell lines, as well as on primary hippocampal cultures by analysing different toxicological endpoints. We found that DON has an impact on the viability of both glial cell types, as shown by a significant decrease of metabolic activity, and a notable cytotoxic effect, which was stronger in the microglia. In astrocytes, DON caused a G1 phase arrest in the cell cycle and a decrease of cyclic-adenosine monophosphate (cAMP) levels. The pro-inflammatory cytokine tumour necrosis factor (TNF)-α was secreted in the microglia in response to DON exposure. Furthermore, the intermediate filaments of the astrocytic cytoskeleton were disturbed in primary hippocampal cultures, and the dendrite lengths of neurons were shortened. The combined results indicated DON’s considerable potential to interfere with the brain cell physiology, which helps explain the observed in vivo neurotoxicological effects.