Miracle-dz/UniFAR-FTUs huggingface dataset:
Single Nucleotide Polymorphisms in 25-Hydroxyvitamin D3 1-Alpha-Hydroxylase (CYP27B1) Gene: The Risk of Malignant Tumors and Other Chronic Diseases

Vitamin D is widely known for its roles in the promotion of apoptosis and differentiation, with simultaneous inhibition of proliferation, inflammation, angiogenesis, invasion, and metastasis. Modern literature lacks complete information on polymorphisms in CYP27B1, the only enzyme capable of vitamin D activation. This review presents gathered data that relate to genetic variants in CYP27B1 gene in correlation to multiple diseases, mostly concerning colorectal, prostate, breast, lung, and pancreatic cancers, as well as on other pathologies, such as non-Hodgkin’s lymphoma, oral lichen planus, or multiple sclerosis.
Variability in the Management of Adults with Pulmonary Nontuberculous Mycobacterial Disease.

BACKGROUND The increasing global prevalence of pulmonary nontuberculous mycobacteria (NTM) disease has called attention to challenges in NTM diagnosis and management. This study is conducted to understand management and outcomes of patients with pulmonary NTM disease at diverse centers across the US. METHODS We conducted a 10-year (2005-2015) retrospective study at seven Vaccine and Treatment Evaluation Units to evaluate pulmonary NTM treatment outcomes in human immunodeficiency virus-negative adults. Demographic and clinical information were abstracted through medical record review. Microbiologic and clinical cure were evaluated using previously defined criteria. RESULTS Of 297 patients diagnosed with pulmonary NTM, the most frequent NTM species were Mycobacterium avium-intracellulare complex (83.2%), M. kansasii (7.7%), and M. abscessus (3.4%). Two hundred forty-five (82.5%) patients received treatment, while 45 (15.2%) were followed without treatment. Eighty-six patients had available drug susceptibility results; of these, >40% exhibited resistance to rifampin, ethambutol, or amikacin. Of the 138 patients with adequate outcome data, 78 (56.5%) experienced clinical and/or microbiologic cure. Adherence to the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) treatment guidelines was significantly more common in patients who were cured (odds ratio [OR] 4.5, 95% confidence interval [CI] 2.0-10.4, P < 0.001). Overall mortality was 15.7%. CONCLUSIONS Despite ATS/IDSA Guidelines, management of pulmonary NTM disease was heterogeneous and cure rates were relatively low. Further work is required to understand which patients are suitable for monitoring without treatment and the impact of antimicrobial therapy on pulmonary NTM morbidity and mortality.
Association between 8 P‐glycoprotein (MDR1/ABCB1) gene polymorphisms and antipsychotic drug‐induced hyperprolactinaemia

Hyperprolactinaemia, a common adverse effect of antipsychotic drugs, is primarily linked to blockade of dopamine D2 receptors in the pituitary gland. Certain antipsychotic drugs, such as, for example risperidone and paliperidone, are more likely to induce hyperprolactinaemia compared to others. This effect is probably caused by a relatively high blood/brain concentration ratio, a consequence of being a substrate of P‐glycoprotein. Genetic variants of P‐glycoprotein with changed functional activity might influence the potential of risperidone and paliperidone to cause hyperprolactinaemia as the altered blood/brain concentration ratio would lead to a reduced therapeutic drug level within essential brain areas making dose adaptations necessary. This increases exposure of dopamine D2 receptors within the pituitary gland.
Newer Generation of Cementless Total Knee Arthroplasty: A Systematic Review.

INTRODUCTION Although the use of cementless implants in total knee arthroplasty (TKA) has increased in recent years, there is still ongoing debate regarding the optimal method of fixation. The purpose of this review was to evaluate the evidence regarding cementless versus cemented total knee arthroplasty (TKA) with regard to: (1) all-cause survivorship and aseptic survivorship; and (2) patient-reported outcome measures (PROMs) of newer generation TKAs. MATERIALS AND METHODS A systematic review of all reports on cementless TKA published from January 2010 to February 2019 was performed. A total of 221 articles were evaluated and 39 studies met inclusion criteria for final analysis. Metrics evaluated included all-cause survivorship, aseptic survivorship, and Knee Society Scores (KSS). RESULTS Modern cementless TKA provides excellent survivorship and patient-reported outcomes as compared to cemented designs. CONCLUSIONS Recent studies have demonstrated that newer generation cementless TKAs provide similar functional outcomes and survivorship as compared to cemented TKA. However, additional prospective, randomized trials with long-term follow up are necessary to further compare the outcomes of cementless versus cemented TKA.
Treatment of Fabry's Disease With Migalastat: Outcome From a Prospective Observational Multicenter Study (FAMOUS)

Fabry's disease (FD) is an X‐linked lysosomal storage disorder caused by the deficient activity of the lysosomal enzyme α‐galactosidase A (α‐Gal A) leading to intracellular accumulation of globotriaosylceramide (Gb3). Patients with amenable mutations can be treated with migalastat, a recently approved oral pharmacologic chaperone to increase endogenous α‐Gal A activity. We assessed safety along with cardiovascular, renal, and patient‐reported outcomes and disease biomarkers in a prospective observational multicenter study after 12 months of migalastat treatment under “real‐world” conditions. Fifty‐nine (28 females) patients (34 (57.6%) pretreated with enzyme replacement therapy) with amenable mutations were recruited. Migalastat was generally safe and well tolerated. Females and males presented with a reduction of left ventricular mass index (primary end point) (−7.2 and −13.7 g/m2, P = 0.0050 and P = 0.0061). FD‐specific manifestations and symptoms remained stable (all P > 0.05). Both sexes presented with a reduction of estimated glomerular filtration rate (secondary end point) (−6.9 and −5.0 mL/minute/1.73 m2; P = 0.0020 and P = 0.0004, respectively), which was most prominent in patients with low blood pressure (P = 0.0271). α‐Gal A activity increased in male patients by 15% from 29% to 44% of the normal wild‐type activity (P = 0.0106) and plasma lyso‐Gb3 levels were stable in females and males (P = 0.3490 and P = 0.2009). Reevaluation of mutations with poor biochemical response revealed no marked activity increase in a zero activity background. We conclude that therapy with migalastat was generally safe and resulted in an amelioration of left ventricular mass. In terms of impaired renal function, blood pressure control seems to be an unattended important goal.
Common refractive errors among the Ekitis of south-western Nigeria

This study was aimed to report the common refractive errors among the Ekitis of south-western Nigeria. A population based survey of refractive errors. The selection criteria for refraction included complaint bordering on asthenopic symptoms and visual acuity worse than 6/9 that improved with pin hole or near vision worse than N8 at 40 cm but improved with test plus lenses. The study population comprised 123 (30.3%) males and 283 (69.7%) females with age range 14-92, mean 48.29. Presbyopia was the commonest refractive error and astigmatism the least. The commonest prescription was Plano add +1.50DS. The least age of presbyopia was 30. The range of hyperopic refractive power is, +0.50 to +12.00DS. The range of near refractive power is, +1.00 to +3.75DS. Most patients (66.5%) had presbyopic refractive power in the range +1.00DS to +3.75DS while 17.8% had combined hyperopia with presbyopia in the range +0.50DS add +1.00DS to +12.00DS add +2.00DS. The range of myopic refractive power is, - 0.50DS to -8.00DS. Myopia was commoner than hyperopia but, combined errors of hyperopia with presbyopia were commoner than combined myopia with presbyopia. There was no association between gender and refractive error (P=0.894) but there was between age and type of refractive error among the participants (P<0.001). Presbyopia was the commonest refractive error and correlated with the mean age of the cohort. The studied cohort was representative of the population. The refractive powers could be useful in making readymade spectacles for the community.
Effect of Systemic Subnormal Deuterium Level on Metabolic Syndrome Related and other Blood Parameters in Humans: A Preliminary Study

The effects of deuterium depletion on the human organism have been, except for the antitumor action, seldom investigated by now and the available data are scarce. In oncological patients who also suffered from diabetes and were treated with deuterium-depleted water (DDW), an improvement of glucose metabolism was observed, and rat studies also proved the efficacy of DDW to reduce blood sugar level. In the present work, 30 volunteers with pre- or manifest diabetes were enrolled to a clinical study. The patients received 1.5 L of water with reduced deuterium content (104 ppm instead of 145 ppm, equivalent 12 mmol/L in human) daily for 90 days. The effects on fasting glucose and insulin level, on peripheral glucose disposal, and other metabolic parameters were investigated. Fasting insulin and glucose decreased, and insulin reaction on glucose load improved, in 15 subjects, while in the other 15 the changes were opposite. Peripheral glucose disposal was improved in 11 of the subjects. In the majority of the subjects, substantial increase of serum high-density lipoprotein (HDL) cholesterol and significant decrease of serum Na+ concentration were also seen—the latter possibly due to activation of a Na+/H+ antiporter by the decreased intracellular deuterium level. The results support the possible beneficial role of DDW in disorders of glucose metabolism but leave questions open, requiring further studies.
The Radial Piezoelectric Response from Three-Dimensional Electrospun PVDF Micro Wall Structure

The ability of electrospun polyvinylidene fluoride (PVDF) fibers to produce piezoelectricity has been demonstrated for a while. Widespread applications of electrospun PVDF as an energy conversion material, however, have not materialized due to the random arrangement of fibers fabricated by traditional electrospinning. In this work, a developed 3D electrospinning technique is utilized to fabricate a PVDF micro wall made up of densely stacked fibers in a fiber-by-fiber manner. Results from X-ray diffraction (XRD) and Fourier transform infrared spectra (FTIR) demonstrate that the crystalline structure of this PVDF wall is predominant in the β phase, revealing the advanced integration capability of structural fabrication and piezoelectric poling with this 3D electrospinning. The piezoelectric response along the radial direction of these PVDF fibers is measured while the toppled micro wall, comprised of 60 fibers, is sandwich assembled with a pair of top/bottom electrodes. The measured electrical output is ca. 0.48 V and 2.7 nA. Moreover, after constant mechanical compression happening over 10,000 times, no obvious reduction in the piezoelectric response has been observed. The combined merits of high-precision 3D fabrication, in situ piezoelectric poling, and high mechanical robust make this novel structure an attractive candidate for applications in piezoelectric energy harvesting and sensing.
Automated thresholding algorithms outperform manual thresholding in macular optical coherence tomography angiography image analysis

Introduction For quantification of Optical Coherence Tomography Angiography (OCTA) images, Vessel Density (VD) and Vessel Skeleton Density (VSD) are well established parameters and different algorithms are in use for their calculation. However, comparability, reliability and ability to discriminate healthy and impaired macular perfusion of different algorithms are unclear, yet, of potential high clinical relevance. Hence, we assessed comparability and test-retest reliability of the most common approaches. Materials and methods Two consecutive 3×3mm OCTA en face images of the superficial and deep retinal layer were acquired with swept-source OCTA. VD and VSD were calculated with manual thresholding and six automated thresholding algorithms (Huang, Li, Otsu, Moments, Mean, Percentile) using ImageJ and compared in terms of intra-class correlation coefficients, measurement differences and repeatability coefficients. Receiver operating characteristic analyses (healthy vs. macular pathology) were performed and Area Under the Curve (AUC) values were calculated. Results Twenty-six eyes (8 female, mean age: 47 years) of 15 patients were included (thereof 15 eyes with macular pathology). Binarization thresholds, VD and VSD differed significantly between the algorithms and compared to manual thresholding (p < 0.0001). Inter-measurement differences did not differ significantly between patients with healthy versus pathologic maculae (p ≥ 0.685). Reproducibility was higher for the automated algorithms compared to manual thresholding on all measures of reproducibility assessed. AUC was significantly higher for the Mean algorithm compared to the manual approach with respect to the superficial retinal layer. Conclusions Automated thresholding algorithms yield a higher reproducibility of OCTA parameters and allow for a more sensitive diagnosis of macular pathology. However, different algorithms are not interchangeable nor results readily comparable. Especially the Mean algorithm should be investigated in further detail. Automated thresholding algorithms are preferable but more standardization is needed for clinical use.
Drosophila-associated bacteria differentially shape the nutritional requirements of their host during juvenile growth

The interplay between nutrition and the microbial communities colonizing the gastrointestinal tract (i.e., gut microbiota) determines juvenile growth trajectory. Nutritional deficiencies trigger developmental delays, and an immature gut microbiota is a hallmark of pathologies related to childhood undernutrition. However, how host-associated bacteria modulate the impact of nutrition on juvenile growth remains elusive. Here, using gnotobiotic Drosophila melanogaster larvae independently associated with Acetobacter pomorumWJL (ApWJL) and Lactobacillus plantarumNC8 (LpNC8), 2 model Drosophila-associated bacteria, we performed a large-scale, systematic nutritional screen based on larval growth in 40 different and precisely controlled nutritional environments. We combined these results with genome-based metabolic network reconstruction to define the biosynthetic capacities of Drosophila germ-free (GF) larvae and its 2 bacterial partners. We first established that ApWJL and LpNC8 differentially fulfill the nutritional requirements of the ex-GF larvae and parsed such difference down to individual amino acids, vitamins, other micronutrients, and trace metals. We found that Drosophila-associated bacteria not only fortify the host’s diet with essential nutrients but, in specific instances, functionally compensate for host auxotrophies by either providing a metabolic intermediate or nutrient derivative to the host or by uptaking, concentrating, and delivering contaminant traces of micronutrients. Our systematic work reveals that beyond the molecular dialogue engaged between the host and its bacterial partners, Drosophila and its associated bacteria establish an integrated nutritional network relying on nutrient provision and utilization.
Synaptic Specificity and Application of Anterograde Transsynaptic AAV for Probing Neural Circuitry

Revealing the organization and function of neural circuits is greatly facilitated by viral tools that spread transsynaptically. Adeno-associated virus (AAV) exhibits anterograde transneuronal transport, however, the synaptic specificity of this spread and its broad application within a diverse set of circuits remains to be explored. Revealing the organization and function of neural circuits is greatly facilitated by viral tools that spread transsynaptically. Adeno-associated virus (AAV) exhibits anterograde transneuronal transport, however, the synaptic specificity of this spread and its broad application within a diverse set of circuits remains to be explored. Here, using anatomic, functional, and molecular approaches, we provide evidence for the preferential transport of AAV1 to postsynaptically connected neurons and reveal its spread is strongly dependent on synaptic transmitter release. In addition to glutamatergic pathways, AAV1 also spreads through GABAergic synapses to both excitatory and inhibitory cell types. We observed little or no transport, however, through neuromodulatory projections (e.g., serotonergic, cholinergic, and noradrenergic). In addition, we found that AAV1 can be transported through long-distance descending projections from various brain regions to effectively transduce spinal cord neurons. Combined with newly designed intersectional and sparse labeling strategies, AAV1 can be applied within a wide variety of pathways to categorize neurons according to their input sources, morphology, and molecular identities. These properties make AAV1 a promising anterograde transsynaptic tool for establishing a comprehensive cell-atlas of the brain, although its capacity for retrograde transport currently limits its use to unidirectional circuits. SIGNIFICANCE STATEMENT The discovery of anterograde transneuronal spread of AAV1 generates great promise for its application as a unique tool for manipulating input-defined cell populations and mapping their outputs. However, several outstanding questions remain for anterograde transsynaptic approaches in the field: (1) whether AAV1 spreads exclusively or specifically to synaptically connected neurons, and (2) how broad its application could be in various types of neural circuits in the brain. This study provides several lines of evidence in terms of anatomy, functional innervation, and underlying mechanisms, to strongly support that AAV1 anterograde transneuronal spread is highly synapse specific. In addition, several potentially important applications of transsynaptic AAV1 in probing neural circuits are described.
Perceived addiction to vaping among youth and young adult regular vapers

Background The prevalence of e-cigarette use among youth and young adults has increased markedly in recent years; however, little is known about young people’s perceptions of e-cigarette addiction. This study examines factors associated with self-reported addiction to e-cigarette use among this population. Methods In 2018, 1048 Canadians aged 16–25 years were recruited through online social media platforms to complete a survey. Quota sampling was used to oversample regular e-cigarette users (vaping at least weekly); these 578 regular users were included in this analysis. Self-perceived addiction was assessed by asking participants if they felt they were ‘very’, ‘somewhat’ or ‘not at all’ addicted to e-cigarettes. A proportional odds model was employed to identify factors associated with the ordinal outcome. Results Almost half of regular users perceived themselves to be ‘not at all addicted’, 41% felt they were ‘somewhat addicted’ and 13% felt they were very addicted to e-cigarettes. Women, former cigarette smokers, daily vapers and those vaping for more than a year were more likely to report higher levels of perceived addiction. Similarly, high sensation-seeking youth, those reading blogs and websites about vaping, those frequently dripping and those using higher nicotine strengths had a greater likelihood of higher perceived addiction than their respective counterparts. Conclusion More than half of youth and young adult regular e-cigarette users felt they had some level of addiction. The findings identify possible opportunities for targeted programming for education and treatment, as well as potential opportunities for policy change such as maximum allowable nicotine strengths.
MicroRNA (miRNA): A New Dimension in the Pathogenesis of Antiphospholipid Syndrome (APS)

MicroRNAs (miRNAs) are single-stranded, endogenous RNA molecules that play a significant role in the regulation of gene expression as well as cell development, differentiation, and function. Recent data suggest that these small molecules are responsible for the regulation of immune responses. Therefore, they may act as potent modulators of the immune system and play an important role in the development of several autoimmune diseases. Antiphospholipid syndrome (APS) is an autoimmune systemic disease characterized by venous and/or arterial thromboses and/or recurrent fetal losses in the presence of antiphospholipid antibodies (aPLs). Several lines of evidence suggest that like other autoimmune disorders, miRNAs are deeply involved in the pathogenesis of APS, interacting with the function of innate and adaptive immune responses. In this review, we characterize miRNAs in the light of having a functional role in the immune system and autoimmune responses focusing on APS. In addition, we also discuss miRNAs as potential biomarkers and target molecules in treating APS.
COVID-19 in gastroenterology: a clinical perspective

We read with interest the article ‘Diarrhoea may be underestimated: a missing link in 2019 novel coronavirus’ by Liang et al . 1 Indeed, we agree with the authors that diarrhoea may be an underestimated and under-reported symptom of coronavirus disease 2019 (COVID-19). Similar to data from China, fever and cough are the two most commonly reported symptoms of COVID-19 in Singapore; around 30% of cases were afebrile, which may have been due to intensive efforts at contact tracing.2 3 In contrast, while gastrointestinal symptoms appear to be infrequent in China (nausea and vomiting: 5.0% and diarrhoea: 3.7%), 17% of patients with COVID-19 in Singapore reported diarrhoea.3 Interestingly, SARS-CoV2 RNA was detected in 50% of patients’ stool samples but was not clearly associated with abdominal symptoms. In those with detectable faecal virus RNA, approximately half had diarrhoea and half had normal stool consistency. Besides the gut, studies suggest SARS-CoV2 …
Circular RNA-ABCB10 suppresses hepatocellular carcinoma progression through upregulating NRP1/ABL2 via sponging miR-340-5p/miR-452-5p.

OBJECTIVE Hepatocellular carcinoma (HCC) is one of the most common liver malignancies worldwide with a high rate of recurrence and mortality. Circular RNA-ABCB10 (circ-ABCB10), 724 nucleotides in length, plays a pro-oncogenic role in tumor progression. However, the role of circ-ABCB10 in HCC is still unknown. Therefore, the objective of this study was to determine the role of circ-ABCB10 in HCC progression in vitro and in vivo and to elucidate the underlying mechanism. PATIENTS AND METHODS Tumor tissues from patients with HCC and multiple HCC cell lines were used for in vitro experiments and a mouse xenograft model was used for in vivo experiments. Quantitative Real Time-PCR, Western blots, lentivirus transfection, cell proliferation assays, cloning formation, migration, and invasion assays, flow cytometry, Luciferase reporter assays, and biotin-coupled probe pull-down assays were performed to investigate the mechanism underlying the effect of circ-ABCB10 on HCC. RESULTS The results revealed that the expression of circ-ABCB10 was downregulated in both HCC tissues and cell lines and was positively correlated with histological grade and tumor size. The overexpression of circ-ABCB10 exerted inhibitory effects on HCC cell proliferation, invasion, and migration. Mechanistic and functional evidence together showed that circ-ABCB10 elevated expressions of neuropilin-1 (NRP1) and ABL related gene (ABL2) by sponging miR-340-5p and miR-452-5p, which inhibited the progression of HCC. Furthermore, the in vivo study suggests that circ-ABCB10 inhibited tumor growth in nude mice. CONCLUSIONS In brief, the results demonstrate that circ-ABCB10 exerts anti-tumor roles via miR-340-5p/miR-452-5p-NRP1/ABL2 signaling axis, providing a promising biomarker and therapeutic target for HCC.