Miracle-dz/UniFAR-FTUs huggingface dataset:
CBS-Induced H2S Generation in Hippocampus Inhibits EA-Induced Analgesia

Hydrogen sulfide (H2S) is an important mediator participating in both physiological and pathological systems and related to the inflammatory process. Acupuncture has a therapeutic effect on inflammatory pain. However, whether H2S generated in the central nervous system (CNS) is a mediator of electroacupuncture (EA) treatment for inflammatory pain is unknown. We injected complete Freund's adjuvant (CFA) to induce inflammatory pain and applied EA treatment as an interventional strategy for pain relief. The results presented here show that S-adenosyl-l-methionine (SAM), an allosteric activator of cystathionine-β-synthetase (CBS), may reverse the therapeutic effect of EA. CBS-induced H2S generation might get involved in the mechanism of EA-induced analgesia in the hippocampus on chronic inflammatory pain.
Naturally Occurring Microbiota Associated with Mosquito Breeding Habitats and Potential Parasitic Species against Mosquito Larvae: A Study from Gampaha District, Sri Lanka

A mosquito species has its own favourable requirements of abiotic and biotic characteristics including microbiota, in a breeding habitat. Some of the microbiota may cause parasitic or pathogenic effects to mosquito larvae such as species of viruses, parasitic bacteria, fungi, protists, entomopathogenic nematodes, and filamentous fungi. In Sri Lanka, there is a scarcity of information on microbiota associated with mosquito breeding habitats and their effect on mosquito larvae. Hence, the present study was conducted to determine microbiota species/taxa associated with a variety of mosquito breeding habitats in selected areas of the Gampaha District in Sri Lanka and the relationship, if any, the microbiota has with mosquito larva survival and breeding. Forty-five microbiota species belonging to 11 phyla were found from different mosquito breeding habitats with the highest percentage belonging to phylum Euglenozoa (27.89%). Species that belonged to the phylum Amoebozoa (1.22%) and Sarcodina (1.17%) had the lowest abundance, and each of its species richness was recorded as one. Philodina citrina followed by Monostyla bulla comprised 30.8% and 16.59%, respectively, of the total rotifer population. From the total microbiota, 25-50% existed as accidental while less than 25% rare, in the habitat type according to their abundance. Paddy fields had the highest species richness (17), evenness (23.52), Shannon-Weiner (66.64), and beta diversity (0.65) over 50% indicating high heterogeneity in microbiota composition among the habitats. Ciliated protists, namely, Vorticella microstoma, Zoothamnium spp. , and Chilodinella sp. , were identified as naturally occurring microbiota associated with Culex mosquito larvae that inhabited in paddy fields and associated irrigation canals. Only Vorticella microstoma caused a significant lethal effect on mosquito larvae. This study revealed that species of Cx. gelidus, Cx. pseudovishnui, Cx. tritaeniorhynchus, Cx. quinquefasciatus, and Cx. whitmorei served as hosts for V. microstoma where infectivity rate in Cx. tritaeniorhynchus reached 73.22. Chilodinella sp. selectively served as endoparasitic to Cx. gelidus larvae causing only 4.58% mortality, and invasive cysts of the pathogen were observed in the subcuticular layer of the host body. Even though Zoothamnium spp. were found on Cx. tritaeniorhynchus larvae, there was no lethal effect due to the attachment of the parasitic agent. The potential of these microbiotas in integrated vector controlling approaches in future perspectives is recommended.
FAUNAL ASSEMBLAGES AND DISTRIBUTIONAL SHIFTS OF COLEOPTERA DURING THE LATE PLEISTOCENE IN CANADA AND THE NORTHERN UNITED STATES

Abstract A faunal list of 362 sub-fossil Coleoptera obtained from 33 published and 24 unpublished sites of Pleistocene age in Canada and the neighbouring United States is given. A table indicates the distribution of families, with the number of species encountered, through discrete intervals of Pleistocene time. Seven species representing members of the Carabidae, Hydrophilidae, Staphylinidae, and Scolytidae have been used to illustrate distribution changes through the last interglacial/glacial/present interglacial cycle. The maximum distance so far recorded is a shift of over 9000 km for Anotylus gibbulus (Epp.), a staphylinid, found fossil in Toronto during the last interglacial, and today recorded only from Eurasia and Asia. A number of other species whose modern ranges are confined to northwestern North America have been found fossil in the Great Lakes – St. Lawrence region, over 4000 km distant. A similar shift is noted in species which today are found only in the eastern Canadian Arctic. Aspects of ice build up, marginal conditions outside the Laurentide Ice Sheet limits, Pleistocene climates, paleoecology, and sub-fossil insect localities are used to formulate hypotheses about three refugia around the perimeter of the Late Wisconsinan ice.
Somatic Acupoint Stimulation for Cancer-Related Sleep Disturbance: A Systematic Review of Randomized Controlled Trials

Aim The aim of this systematic review was to analyze and synthesize available evidence for the effects of somatic acupoint stimulation (SAS) on cancer-related sleep disturbance in adults with cancer. Methods Nine databases and four clinical trial registries were searched from their inception to July 2019 to identify potential articles and registered trials. Two authors independently extracted data and appraised the methodological quality of the included studies. The included studies could not be subjected to meta-analysis due to the significant variations in SAS intervention protocols and outcome measurement instruments. This systematic review therefore reported the results of the included trials narratively. Results Seven studies were identified, which involved 906 cancer patients. SAS protocols varied across trials without an optimal evidence-based standard intervention protocol to manage cancer-related sleep disturbance. Sanyinjiao (SP6) was the most commonly selected acupoint. Manual acupuncture was typically 15–30 min in duration and was conducted once a day or once a week for a period of 1–5 weeks, whereas self-administered acupressure was typically 1–3 min in duration per point and was conducted once a day, such as during night time before going to bed, for a period of 1–5 months. The results indicated that SAS could potentially relieve cancer-related sleep disturbance and improve quality of life. Mild adverse effects were reported in three of the included studies, but none of them performed a causality analysis to clarify the association between the reported adverse events and the intervention. Conclusions This systematic review showed that SAS is a useful approach to relieving cancer-related sleep disturbance. However, research evidence on SAS for managing cancer-related sleep disturbance has not been fully conclusive due to the limited number of existing clinical studies with relatively small sample size and suboptimal methodological quality. Clinical trials with large sample size and robust methodology are warranted in future research.
Association of Noncognitive Life Skills With Mortality at Middle and Older Ages in England

Key Points Question Are greater noncognitive life skills associated with reduced mortality in older adults? Findings In this cohort study of 7850 adults aged 52 years and older followed up for approximately 7 years, the combination of conscientiousness, emotional stability, persistence, optimism, and sense of control was associated with reduced mortality independently of sociodemographic, health, and behavioral factors, but no single life skill explained the association. Meaning These findings suggest that higher levels of noncognitive life skills are associated with longer survival, suggesting that maintenance of these skills in later life is relevant to health.
Topical Anti-Inflammatory Activity of Essential Oils of Alpinia calcarata Rosc., Its Main Constituents, and Possible Mechanism of Action

This study aimed at investigating the anti-inflammatory potential of essential oil from rhizome and leaf of Alpinia calcarata Rosc. (ACEO) with the focus of its topical anti-inflammatory activity along with its dominant compounds 1,8-cineole and α-terpineol using mouse ear edema model. ACEOs were analyzed by GC-MS. The anti-inflammatory activity was determined by studying the inhibition of overproduction of proinflammatory mediators—nitric oxide, reactive oxygen species, prostaglandins, cyclooxygenases, and cytokines induced by lipopolysaccharides in murine macrophages. Topical anti-inflammatory and antinociceptive activity was studied by 12-O-tetradecanoylphorbol-13-acetate (TPA) induced skin inflammation and formalin-induced pain model in mice, respectively. Rhizome oil has 1,8-cineole (31.08%), α-terpineol (10.31%), and fenchyl acetate (10.73%) as major compounds whereas the ACEO from leaves has 1,8-cineole (38.45%), a-terpineol (11.62%), and camphor (10%). ACEOs reduced the production of inflammatory mediators in vitro in a concentration-dependent manner. Further, ACEO and its major compounds reduced ear thickness, weight, myeloperoxidase, and cytokines significantly (p < 0.01) in mouse ear. Dose-dependent reduction in flinching and licking in both the phases of pain sensation concludes the topical analgesic effect. Our findings suggest the potency of topical use of ACEOs for inflammatory disease conditions.
Image quality and radiation exposure with low-contrast-dose computed tomography angiography of the lower extremities

Introduction Multidetector computed tomography is the reference standard for the diagnosis of peripheral arterial disease (PAD). The aim of this study is to optimise the image quality of computed tomography (CT) scanning for the diagnosis of PAD with the lowest possible radiation and contrast volume. Material and methods Seventy-two patients were referred for evaluation of suspected PAD with CT angiography. Patients were randomly assigned to an optimise care dose of kVp – group A, n = 36; 18 men, 18 women; mean age, 63 years with standard deviation 15; range, 20-88 years (contrast volume 80-85 ml was injected automatically with bolus tracking, and group B, n = 36; 18 men, 18 women; mean age, 61 years with standard deviation 16; range, 26-88 years (contrast volume 120-140 ml was injected automatically with bolus tracking). Other scanning parameters were kept constant. Lower extremities vessel enhancement and image noise were quantified, and the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Subjective vessel contrast was assessed by two radiologists in consensus. Result A total of 16 cases of PAD (22.2%) were found in the evaluated of subjects (10 in group A, and six in group B). All PAD cases were detected by the two readers. There was no significant difference in the size or location of the PAD between the two groups; the average image noise was 19 HU for group A and 16 HU for group B. The difference was not statistically significant (p = 0.183). Overall, the SNR and CNR were slightly higher in group B (25.5 and 24.1, respectively) compared with group A (20 and 17.4, respectively), but those differences were not statistically significant (p = 061 and p = 0.38, respectively). Conclusions All patients were evaluated by lower extremities CTA protocol allowing similar image quality to be achieved in both groups, with optimised care dose for both protocols, and contrast volume was reduced by 40% in the new protocol group compared to the conventional protocol group.
High Glucose Induces the Loss of Retinal Pericytes Partly via NLRP3-Caspase-1-GSDMD-Mediated Pyroptosis

Diabetic retinopathy (DR) is one of the hallmark complications of diabetes and a leading cause of vision loss in adults. Retinal pericyte death seems to be a prominent feature in the onset of DR. Pyroptosis is an inflammatory form of programmed cell death, defined as being caspase-gasdermin-D (GSDMD)-dependent. The NOD-like receptor pyrin 3 (NLRP3) inflammasome plays an important role in mediating GSDMD activation. However, the role and mechanism of pyroptosis in the loss of retinal pericytes during the pathogenesis of DR are still unclear. In the present study, we cultured primary human retinal pericytes (HRPs) in high glucose medium; caspase-3 inhibitor DEVD, caspase-1 inhibitor YVAD, or NLRP3 inhibitor glyburide was used as intervention reagents; GSDMD was overexpressed or suppressed by transfection with an expressing vector or retroviral silencing of GSDMD, respectively. Our data showed that high glucose induced NLRP3-caspase-1-GSDMD activation and pore formation in a dose- and time-dependent manner (p < 0.05) and resulted in the inflammatory cytokines IL-1β and IL-18 and lactate dehydrogenase (LDH) release from HRPs (p < 0.05), which are all signs of HRP pyroptosis. Overexpression of GSDMD facilitated high glucose-induced pyroptosis (all p < 0.05). However, these effects were blunted by synergistically treating DEVD, YVAD, and silencing GSDMD (p < 0.05). Taken together, our results firstly revealed that high glucose induced the loss of retinal pericytes partly via NLRP3-caspase-1-GSDMD-mediated pyroptosis.
Demonstration of a role for α-synuclein as a functional microtubule-associated protein

α-Synuclein is a major constituent of pathological intracellular inclusion bodies, a common feature of several neu- rodegenerative diseases. Two missense mutations in the α-synuclein gene have been identified in confirmed autosomal-dominant familial Parkinson's disease, which segregate with the illness. However, the physiological function of α-synuclein remains unknown. After biochemical investigations we have revealed tubulin to be an α-synuclein associated/binding protein. Here, we show that α-synuclein induces polymerization of purified tubulin into microtubules. Mutant forms of α-synuclein lose this potential. The binding site of α-synuclein to tubulin is identified, and co-localization of α-synuclein with microtubules is shown in cultured cells. To our knowledge, this is the first demonstration of microtubule-polymerizing activity of α-synuclein. Now we can see a striking resemblance between α-synuclein and tau: both have the same physiological function and pathological features, making abnormal structures in diseased brains known as synucleinopathies and tauopathies. The discovery of a physiological role for α-synuclein may provide a new dimension in researches into the mechanisms of α-synuclein-associated neurodegenerative diseases.
Epigenome-Wide Tobacco-Related Methylation Signature Identification and Their Multilevel Regulatory Network Inference for Lung Adenocarcinoma

Tobacco exposure is one of the major risks for the initiation and progress of lung cancer. The exact corresponding mechanisms, however, are mainly unknown. Recently, a growing body of evidence has been collected supporting the involvement of DNA methylation in the regulation of gene expression in cancer cells. The identification of tobacco-related signature methylation probes and the analysis of their regulatory networks at different molecular levels may be of a great help for understanding tobacco-related tumorigenesis. Three independent lung adenocarcinoma (LUAD) datasets were used to train and validate the tobacco exposure pattern classification model. A deep selecting method was proposed and used to identify methylation signature probes from hundreds of thousands of the whole epigenome probes. Then, BIMC (biweight midcorrelation coefficient) algorithm, SRC (Spearman's rank correlation) analysis, and shortest path tracing method were explored to identify associated genes at gene regulation level and protein-protein interaction level, respectively. Afterwards, the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis and GO (Gene Ontology) enrichment analysis were used to analyze their molecular functions and associated pathways. 105 probes were identified as tobacco-related DNA methylation signatures. They belong to 95 genes which are involved in hsa04512, hsa04151, and other important pathways. At gene regulation level, 33 genes are uncovered to be highly related to signature probes by both BIMC and SRC methods. Among them, FARSB and other eight genes were uncovered as Hub genes in the gene regulatory network. Meanwhile, the PPI network about these 33 genes showed that MAGOH, FYN, and other five genes were the most connected core genes among them. These analysis results may provide clues for a clear biological interpretation in the molecular mechanism of tumorigenesis. Moreover, the identified signature probes may serve as potential drug targets for the precision medicine of LUAD.
Sacral Erector Spinae Plane Block for Gender Reassignment Surgery

The erector spinae plane block (ESPB) is an interfascial plane block that has been used to provide perioperative analgesia for a variety of indications. This case report describes the novel use of the sacral ESPB on a transgender patient undergoing male-to-female gender reassignment surgery for perioperative pain control. The sacral ESPB technique was described and post-operative pain score and opioid requirements were reported. The sacral ESPB was successfully used as an alternative to neuraxial, caudal, or peripheral nerve blocks for gender reassignment surgery.
Effectiveness and Safety of Acupuncture and Moxibustion for Primary Dysmenorrhea: An Overview of Systematic Reviews and Meta-Analyses

Background Acupuncture and moxibustion have been accepted as treatment options for primary dysmenorrhea (PD). So far, several systematic reviews (SRs) and meta-analyses (MAs) have reported on the efficacy and safety of acupuncture and moxibustion in treating PD. Objectives The aim of this study was to critically summarize the evidence from relevant SRs and MAs reporting on the efficacy and safety of acupuncture and moxibustion in treatment of PD. Materials and Methods Seven electronic databases, including Cochrane Database of Systematic Reviews, EMBASE, PubMed, SinoMed, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), and Wanfang database, were systematically searched. SRs or MAs about acupuncture for PD published up to May 2019 were included in the analysis. More than two authors independently assessed the quality of the evidence by AMSTAR2, PRISMA, PRISMA-A, and GRADE approach. Results A total of 28 SRs and MAs, 281 original studies, reporting on 26,459 female patients were analyzed. The majority of the SRs were of moderate reporting quality and poor methodological quality. Moderate-quality evidence suggested that acupuncture and moxibustion were more effective compared to indomethacin or Fenbid in treating PD. Low-quality evidence suggested that, compared to NSAIDs, acupuncture and moxibustion could relieve pain with less adverse effects. Conclusion Acupuncture and moxibustion seem to be effective and safe approaches in treatment of PD; yet, the methodological quality of most of the studies and the quality of evidence were low. Thus, additional studies are required to further confirm these results.
Multi-Source Transfer Learning via Ensemble Approach for Initial Diagnosis of Alzheimer’s Disease

Alzheimer’s disease (AD) is one of the most common progressive neurodegenerative diseases, and the number of AD patients has increased year after year with the global aging trend. The onset of AD has a long preclinical stage. If doctors can make an initial diagnosis in the mild cognitive impairment (MCI) stage, it is possible to identify and screen those at a high-risk of developing full-blown AD, and thus the number of new AD patients can be reduced. However, there are problems with the medical datasets including AD data, such as insufficient number of samples and different data distributions. Transfer learning, which can effectively solve the problem of distribution discrepancy between training and test data and an insufficient number of target samples, has attracted increasing attention over recent years. In this paper, we propose a multi-source ensemble transfer learning (METL) approach by introducing ensemble learning and our tri-transfer model that uses Tri-Training, which ensures the transferability of source data by the tri-transfer model and high performance through ensemble learning. The experimental results on the benchmark and AD datasets demonstrate that our proposed approach has effective transferability, robustness, and feasibility, and is superior to existing algorithms. Based on METL, we propose an auxiliary diagnosis system for the initial diagnosis of AD, which helps doctors identify patients in the MCI stage as quickly as possible and with high accuracy so that measures can be taken to prevent or delay the occurrence of AD.
Diagnosis of COVID-19: Considerations, controversies and challenges

Coronavirus disease 2019 (COVID-19) due to a novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic that has resulted in over 1.5 million confirmed cases and close to 100 000 deaths. In the majority of symptomatic cases, COVID-19 results in a mild disease predominantly characterised by upper respiratory tract symptoms. Reverse transcription polymerase chain reaction (RT-PCR) using a nasopharyngeal sample is the mainstay of diagnosis, but there is an ~30% false negative rate early in the disease and in patients with mild disease, and therefore repeat testing may be required. RT-PCR positivity can persist for several days after resolution of symptoms. IgM and IgG antibody responses become positive several days after the onset of symptoms, and robust antibody responses are detectable in the second week of illness. Antibody-based immunoassays have a limited role in the diagnosis of early symptomatic disease. However, their incremental benefit over RT-PCR in the first 2 weeks of illness is currently being clarified in ongoing studies. Such assays may be useful for surveillance purposes. However, their role in potentially selecting individuals who may benefit from vaccination, or as a biomarker identifying persons who could be redeployed into essential employment roles, is being investigated. Rapid antibody-based immunoassays that detect viral antigen in nasopharyngeal samples are being developed and evaluated.
Role of NDP- and FZD4-Related Novel Mutations Identified in Patients with FEVR in Norrin/β-Catenin Signaling Pathway

Mutations in NDP and FZD4 have been closely related to a series of retinal diseases including familial exudative vitreoretinopathy (FEVR). Our study was designed to identify novel NDP and FZD4 mutations by whole exome sequencing (WES) in a cohort of patients with a definitive diagnosis of FEVR and explore the underlying molecular mechanism. During 2016, we investigated fifty nonconsanguineous families with affected individuals exhibiting FEVR phenotype and WES identified one recently reported mutation: NDP c.127C>A (p.H43N), and five novel mutations: NDP c. 129_131del (p.44del), NDP c. 320_353del (p.R107Pfs), NDP c.321delG (p.L108Cfs), NDP c.377G>T (p.C126F), and FZD4 c.314T>G (p.M105R) that cosegragated with the abnormal fundus vascular manifestations in six families. All the mutations were perceived to be pathogenic or likely pathogenic according to the standards and guidelines from the American College of Medical Genetics and Genomics (ACMG) and predicted to be deleterious by a series of bioinformatics analyses. We systematically performed functional analyses on the six mutations utilizing the Topflash reporter assay, where all NDP and FZD4 mutants revealed at least 50% loss of wild-type activity. Immunoprecipitation finally demonstrated that the six mutations could degrade the Norrin-Frizzled-4 pair-binding effect to varying degrees. Finally, our study underscores the correlation between the FEVR phenotype and genotype in NDP and FZD4, extending the mutation spectrum, allowing a reliable assessment of FEVR recurrence and improving genetic counseling. Further, our findings provide essential evidence for the follow-up study of animal models and drug targets by Topflash assays and immunoprecipitation.