Miracle-dz/UniFAR-FTUs huggingface dataset:
DNA Methylation As an Epigenetic Mechanism in the Development of Multiple Sclerosis

The epigenetic mechanisms of gene expression regulation are a group of the key cellular and molecular pathways that lead to inherited alterations in genes’ activity without changing their coding sequence. DNA methylation at the C5 position of cytosine in CpG dinucleotides is amongst the central epigenetic mechanisms. Currently, the number of studies that are devoted to the identification of methylation patterns specific to multiple sclerosis (MS), a severe chronic autoimmune disease of the central nervous system, is on a rapid rise. However, the issue of the contribution of DNA methylation to the development of the different clinical phenotypes of this highly heterogeneous disease has only begun to attract the attention of researchers. This review summarizes the data on the molecular mechanisms underlying DNA methylation and the MS risk factors that can affect the DNA methylation profile and, thereby, modulate the expression of the genes involved in the disease’s pathogenesis. The focus of our attention is centered on the analysis of the published data on the differential methylation of DNA from various biological samples of MS patients obtained using both the candidate gene approach and high-throughput methods.
Hardiness and attitudes toward professional healthcare services: Implications for healthcare service utilization among Black American adults

This study (N = 780) examines the indirect effects of hardiness—health locus of control (HLOC), health competence (HC), health value (HV)—on past-year healthcare provider visit via attitudes toward seeking and receiving professional healthcare services (ATSRPHS). Across four health domains (dental, general health, mental, vision), ATSRPHS mediated the indirect effect of (1) HV and (2) internal HLoC on past-year healthcare provider visit. ATSRPHS also mediated the indirect effect of external HLoC on past-year visit to healthcare provider visit for general medical, mental, and vision health. ATSRPHS did not mediate any indirect effect of HC on past-year healthcare provider visit. This research contributes to understanding determinants of healthcare service utilization among Black American adults.
Improving Symptoms of Peripheral Artery Disease With Hirudotherapy

Peripheral artery disease (PAD) is a significant cause of morbidity and mortality in the world. Critical limb ischemia is a complication of PAD that leads to severe pain at rest, numbness, and absent or diminished pulses in the legs or feet. Revascularization with surgery or endovascular intervention is required to re-establish blood flow to the affected areas. Failure to respond to medical and/or surgical treatment can lead to amputations. The decision to amputate one’s limb can be very challenging. Here, we report a patient with critical limb ischemia who refused a below-the-knee amputation and self-treated with medicinal leech therapy, or hirudotherapy. His symptoms including his pain, burning, and numbness improved significantly following six months of therapy.
The complete mitochondrial genome of Indian Cuckoo Cuculus micropterus (Aves: Cuculiformes)

Abstract The Indian Cuckoo, Cuculus micropterus, belongs to the family Cuculidae. In this paper, we sequenced and analysized the complete mitochondrial genome of C. micropterus. The complete mitochondrial genome of C. micropterus is 17,541 bp in length, which was submitted to the NCBI database under the accession number MZ048030. It contains 13 protein-coding genes, 22 transfer RNA genes, two ribosome RNA genes, and one non-coding control region. The overall base composition of the mitochondrial DNA is 33.2% for A, 24.2% for T, 29.8% for C, and 12.8% for G, with a GC content of 42.6%. In order to explore the molecular phylogenetics evolution of Cuculidae, the nucleotide sequence data of 13 PCGs of C. micropterus and other 11 Cuculiformes were used for the phylogenetic analysis. The result shows that C. micropterus is closely related to Cuculus canorus bakeri. The study contributes to illuminating the taxonomic status of C. micropterus, and may facilitate further investigation of the evolution of Cuculidae.
The Co-Expression of Melanoma-Antigen Family a Proteins and New York Esophageal Squamous Cell Carcinoma-1 in Breast Cancer: A Pilot Study

Objective The aim of this study was to quantify the expression of melanoma-antigen family A proteins (MAGE-A) and New York esophageal squamous cell carcinoma-1 (NY-ESO-1) in breast cancer and establish the prognosis of breast cancer patients with MAGE-A and NY-ESO-1 co-expression. Methods A total of 122 patients with breast cancer were recruited for this study. Their clinicopathological data were collected retrospectively, and the MAGE-A and NY-ESO-1 expressions in paraffin-embedded specimens from the 122 patients were evaluated using immunohistochemical analysis. In addition, the survival states of the patients were recorded. Results Fifty-four patients (44.26%) were MAGE-A positive and 46 (37.70%) were NY-ESO-1 positive. Interestingly, 22 of the 46 NY-ESO-1-positive cases co-expressed MAGE-A. The expression of MAGE-A was positively associated with estrogen-receptor status (χ2 = 4.026, p = 0.045) and human epidermal growth factor receptor 2 status (χ2 = 5.482, p = 0.019), while the expression of NY-ESO-1 was positively associated with p53 expression (χ2 = 4.541, p = 0.033). Of the 122 patients, the lowest survival rate was observed in patients with NY-ESO-1 (+)/MAGE-A (+), with a 5-year survival rate of 59.09% and a median survival of 97 months. Conclusion The results showed that MAGE-A and NY-ESO-1 were frequently expressed in breast cancer patients. The co-expression of MAGE-A and NY-ESO-1 occurred in about 18% of these patients, and it may indicate a poor prognosis.
A phase Ib/IIa trial of 9 repurposed drugs combined with temozolomide for the treatment of recurrent glioblastoma: CUSP9v3

Abstract Background The dismal prognosis of glioblastoma (GBM) may be related to the ability of GBM cells to develop mechanisms of treatment resistance. We designed a protocol called Coordinated Undermining of Survival Paths combining 9 repurposed non-oncological drugs with metronomic temozolomide—version 3—(CUSP9v3) to address this issue. The aim of this phase Ib/IIa trial was to assess the safety of CUSP9v3. Methods Ten adults with histologically confirmed GBM and recurrent or progressive disease were included. Treatment consisted of aprepitant, auranofin, celecoxib, captopril, disulfiram, itraconazole, minocycline, ritonavir, and sertraline added to metronomic low-dose temozolomide. Treatment was continued until toxicity or progression. Primary endpoint was dose-limiting toxicity defined as either any unmanageable grade 3–4 toxicity or inability to receive at least 7 of the 10 drugs at ≥ 50% of the per-protocol doses at the end of the second treatment cycle. Results One patient was not evaluable for the primary endpoint (safety). All 9 evaluable patients met the primary endpoint. Ritonavir, temozolomide, captopril, and itraconazole were the drugs most frequently requiring dose modification or pausing. The most common adverse events were nausea, headache, fatigue, diarrhea, and ataxia. Progression-free survival at 12 months was 50%. Conclusions CUSP9v3 can be safely administered in patients with recurrent GBM under careful monitoring. A randomized phase II trial is in preparation to assess the efficacy of the CUSP9v3 regimen in GBM.
Growth performance and meat quality of meat-type guinea fowl fed different commercial diets

Abstract The aim of study was to assess the growth performance, meat quality, and fatty acid composition of meat-type guinea fowl fed balanced commercial diets under two different feeding programs, similar to those for slaughter turkeys and broiler chickens, respectively. A total of 80 4-week-old meat-type guinea fowl divided into two groups (four replicates per group; 10 birds in each replicate) were raised for 14 weeks. One group received commercially available diets in a three-phased program (TM group), whereas the other group was fed commercial diets in a two-phased program (CM group). Growth-performance-related traits were recorded. At the end of rearing (14 weeks of age), eight birds from each group were slaughtered. Carcass yield and technological traits of meat (pH, color, water-holding capacity, natural and thermal loss, tenderness, fatty acid profile) were analyzed. Groups did not differ in terms of body weight as well as carcass yield and characteristics. There was no difference in meat quality and the fatty acid profile of breast and thigh meat of guinea fowl from TM and CM groups. The findings of this study suggest that both commercial diets (for broiler chickens and turkeys) can be used in meat-type guinea fowl rearing. Due to the lower price of diets fed to the CM group and the lack of significant variation in meat quality traits, its use seems to be more justified from an economic point of view.
Multimorbidity and its effect on perceived burden, capacity and the ability to self-manage in a low-income rural primary care population: A qualitative study

Introduction Multimorbidity is increasing in prevalence, especially in low-income settings. Despite this, chronic conditions are often managed in isolation, potentially leading to burden-capacity imbalance and reduced treatment adherence. We aimed to explore, in a low-income population with common comorbidities, how the specific demands of multimorbidity affect burden and capacity as defined by the Cumulative Complexity Model. Materials and methods Qualitative interviews with thirteen rural community health centre patients in Victoria, Australia. Participants were aged between 47–72 years and reported 3–10 chronic conditions. We asked about perceived capacity and burden in managing health. The Theory of Patient Capacity was used to analyse capacity and Normalisation Process Theory to analyse burden. All data specifically associated with the experience of multimorbidity was extracted from each burden and capacity domain. Results The capacity domains of biography, resource mobilisation and work realisation were important in relation to multimorbidity. Conditions causing functional impairment (e.g. chronic pain, depression) interacted with physical, psychological and financial capacity, leading to biographical disruption and an inability to realise treatment and life work. Despite this, few people had a treatment plan for these conditions. Participants reported that multimorbidity affected all burden domains. Coherence and appraisal were especially challenging due to condition interactions, with clinicians providing little guidance. Discussion The capacity and burden deficits highlighted by participants were not associated with any specific diagnosis, but were due to condition interactions, coupled with the lack of health provider support to navigate interactions. Physical, psychological and financial capacities were inseparable, but rarely addressed or understood holistically. Understanding and managing condition and treatment interactions was a key burden task for patients but was often difficult, isolating and overwhelming. This suggests that clinicians should become more aware of linkages between conditions, and include generic, synergistic or cross-disciplinary approaches, to build capacity, reduce burden and encourage integrated chronic condition management.
Genetic susceptibility to multiple sclerosis in African Americans

Objective To explore the nature of genetic-susceptibility to multiple sclerosis (MS) in African-Americans. Background Recently, the number of genetic-associations with MS has exploded although the MS-associations of specific haplotypes within the major histocompatibility complex (MHC) have been known for decades. For example, the haplotypes HLA-DRB1*15:01~HLA-DQB1*06:02, and HLA-DRB1*03:01~ HLA-DQB1*02:01 have odds ratios (ORs) for an MS-association orders of magnitude stronger than many of these newly-discovered associations. Nevertheless, all these haplotypes are part of much larger conserved extended haplotypes (CEHs), which span both the Class I and Class II MHC regions. African-Americans are at greater risk of developing MS compared to a native Africans but at lesser risk compared to Europeans. It is the purpose of this manuscript to explore the relationship between MS-susceptibility and the CEH make-up of our African-American cohort. Design/methods The African-American (AA) cohort consisted of 1,305 patients with MS and 1,155 controls, who self-identified as being African-American. For comparison, we used the 18,492 controls and 11,144 MS-cases from the predominantly European Wellcome Trust Case Control Consortium (WTCCC) and the 28,557 phased native Africans from the multinational “Be the Match” registry. The WTCCC and the African-Americans were phased at each of five HLA loci (HLA-A, HLA-C, HLA-B, HLA-DRB1 and HLA-DQB1) and the at 11 SNPs (10 of which were in non-coding regions) surrounding the Class II region of the DRB1 gene using previously-published probabilistic phasing algorithms. Results Of the 32 most frequent CEHs, 18 (56%) occurred either more frequently or exclusively in Africans) whereas 9 (28%) occurred more frequently or exclusively in Europeans. The remaining 5 CEHs occurred in neither control group although, likely, these were African in origin. Eight of these CEHs carried the DRB1*15:03~DQB1*06:02~a36 haplotype and three carried the DRB1*15:01~DQB1*06:02~a1 haplotype. In African Americans, a single-copy of the European CEH (03:01_07:02_07:02_15:01_06:02_a1) was associated with considerable MS-risk (OR = 3.30; p = 0.0001)–similar to that observed in the WTCCC (OR = 3.25; p<10−168). By contrast, the MS-risk for the European CEH (02:01_07:02_07:02_15:01_06:02_a1) was less (OR = 1.49; ns)–again, similar to the WTCCC (OR = 2.2; p<10−38). Moreover, four African haplotypes were “protective” relative to a neutral reference, to three European CEHs, and also to the five other African CEHs. Conclusions The common CEHs in African Americans are divisible into those that are either African or European in origin, which are derived without modification from their source population. European CEHs, linked to MS-risk, in general, had similar impacts in African-Americans as they did in Europeans. By contrast, African CEHs had mixed MS-risks. For a few, the MS-risk exceeded that in a neutral-reference group whereas, for many others, these CEHs were “protective”–perhaps providing a partial rationale for the lower MS-risk in African-Americans compared to European-Americans.
Spontaneous perception: a framework for task-free, self-paced perception

Abstract Flipping through social media feeds, viewing exhibitions in a museum, or walking through the botanical gardens, people consistently choose to engage with and disengage from visual content. Yet, in most laboratory settings, the visual stimuli, their presentation duration, and the task at hand are all controlled by the researcher. Such settings largely overlook the spontaneous nature of human visual experience, in which perception takes place independently from specific task constraints and its time course is determined by the observer as a self-governing agent. Currently, much remains unknown about how spontaneous perceptual experiences unfold in the brain. Are all perceptual categories extracted during spontaneous perception? Does spontaneous perception inherently involve volition? Is spontaneous perception segmented into discrete episodes? How do different neural networks interact over time during spontaneous perception? These questions are imperative to understand our conscious visual experience in daily life. In this article we propose a framework for spontaneous perception. We first define spontaneous perception as a task-free and self-paced experience. We propose that spontaneous perception is guided by four organizing principles that grant it temporal and spatial structures. These principles include coarse-to-fine processing, continuity and segmentation, agency and volition, and associative processing. We provide key suggestions illustrating how these principles may interact with one another in guiding the multifaceted experience of spontaneous perception. We point to testable predictions derived from this framework, including (but not limited to) the roles of the default-mode network and slow cortical potentials in underlying spontaneous perception. We conclude by suggesting several outstanding questions for future research, extending the relevance of this framework to consciousness and spontaneous brain activity. In conclusion, the spontaneous perception framework proposed herein integrates components in human perception and cognition, which have been traditionally studied in isolation, and opens the door to understand how visual perception unfolds in its most natural context.
Antilisterial activity of Cymbopogon citratus on crabsticks

Listeria monocytogenes is a gram positive, psychrotrophic, facultative anaerobic bacterium and it is the etiological agent of listeriosis, a severe foodborne disease of major public health concern. There is a rising concern about the cross-contamination of surimi-based products with L. monocytogenes during handling and storage. Lemon grass (Cymbopogon citratus) is known to exhibit strong antimicrobial activity against bacteria due to the presence of citral. The objectives of this research were: (i) to develop a water-based extraction procedure for the antimicrobial component(s) in lemon grass and (ii) to evaluate the antimicrobial effect of a concentrated water-based extract and commercial essential oil (EO) of lemon grass against L. innocua (ATCC 33090), a surrogate strain of L. monocytogenes, in vitro and on crabsticks. Briefly, antilisterial activity of concentrated extract and commercial EO of lemon grass was tested using the agar well diffusion technique. Crabsticks were subsequently inoculated with L. innocua to a final density of ca. 4 log cfu/g and then coated with 500 μl of either concentrated extract or 0.5% commercial EO and stored at 4 °C for up to 15 days. Samples were then subjected to microbiological analysis every 5 days to enumerate counts of Listeria. Following the agar well diffusion assay, inhibition zones with mean diameters of 18.3 and 21.0 mm were obtained with the concentrated extract and commercial EO respectively. The population of L. innocua in WBE-coated (4.2 log cfu/g) and 0.5% EO-coated (2.7 log cfu/g) samples were significantly lower (P < 0.05) after 15 days than their untreated control counterpart (5.2 log cfu/g). Lemon grass extract and essential oil have the potential to control growth of L. monocytogenes in seafood surimi products with minimal adverse effect on the organoleptic characteristics of the product and thus can possibly be used as a natural food preservative.
Death in worship places: Evaluating the roles of religious organisations and state governments in reducing the risks of religious disaster

The numbers of accidents and disasters resulting in injury and death of the faithful in religious buildings in many parts of the world are on the increase in recent years. Interestingly, the citizens of the countries where most of the cases are reported are overtly religious and manifest their religiosity by attending religious activities in religious buildings. This, therefore, heightens the impact of a disaster, such as where there is a religious building collapse or a stampede. The attendant social, legal and economic effects of such disasters on religious organisations, religious faithful and society thus necessitate the study. This article critically examines the roles of religious organisations and state governments in reducing the risks of avoidable disasters in religious buildings. It evaluates the reports of two instances of church building collapses in Nigeria as case studies. This article observes that many religious organisations do not have effective risk and safety policies to reduce their exposure to religious disasters. It also observes that the state is ineffective in enforcing building standards. It argues that religious organisations and the state owe a legal duty to protect the lives and guarantee the safety of the faithful against the tragedy that may occur in worship places, and where this duty is breached, and a victim suffers harm, a right to damages will accrue. It concludes that although a religious organisation may not be able to stop all such disasters, having an effective disaster risk policy can assist in reducing the occurrence of avoidable mishaps in religious buildings.
The Antitumor Activity of CAR-T-PD1 Cells Enhanced by HPV16mE7-Pulsed and SOCS1-Silenced DCs in Cervical Cancer Models

Background Genetically T cells modified with cancer-specific chimeric antigen receptors (CARs) showed great promise in mediate tumor regression, especially in patients with advanced leukemia. However, the therapeutic effect against solid tumors is not as prominent as anticipated to exhibit potent antitumor efficacy. The underlying mechanism maybe attributed to the inhibitory co-stimulatory pathways such as (PD1/PDL1), which provide tumor cells an escape mechanism from immunosurveillance. Therefore, by exchanging the transmembrane and cytoplasmic tail of PD1 with positive costimulatory molecules, such as CD28 and 4–1BB signaling domains (PD1-CD28-4-1BB, PD1-CAR), the T cell-negative co-stimulatory PD1/PDL1 signal pathway was thus converted into a positive one. This study aimed to investigate whether the genetically modified CAR-T-PD1 cells activated by SOCS1 silenced DCs have enhanced anti-neoplastic potential in vitro/in vivo. Methods In order to enhance the antigenicity and reduce transformation activity, a modified HPV16 E7 (HPV16mE7) was employed to load on dendritic cells (DCs) with SOCS1 silenced to improve its antitumor efficiency and targeting ability against cervical cancer. The CAR-T-PD1 cells activated by the generated DCs were transfused into murine models bearing tumor of CaSki cells that expressing PDL1 and HPV16 E6/E7 for in vitro/in vivo antitumor activity assay. Results The data showed that DC-activated CAR-T-PD1 cells significantly increased the secretion of IL-2, IFN-γ and TNF-α, whilst enhanced cytotoxic activity, suppressed tumor growth and prolong the survival time compared with the controls. Conclusion These results indicated that the genetically engineered T cells activated by DCs had improved antitumor efficiency and targeting ability. Furthermore, it was suggested that it may have important implications for the improvement of T cell immunotherapy against cervical cancer.