Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical application of NGS-based SNP haplotyping for the preimplantation genetic diagnosis of primary open angle glaucoma

ABSTRACT The current study describes a successful case of preimplantation genetic diagnosis (PGD) of primary open angle glaucoma (POAG) and verifies the efficiency of next-generation sequencing (NGS)-based haplotyping for PGD of POAG. In this study, we applied NGS as part of PGD to effectively detect POAG prior to embryo implantation and avoid the prospect of pregnancy termination in event of vertical inheritance of POAG. We used the technique of multiple annealing and looping based amplification cycles (MALBAC) to conduct whole genome amplification (WGA) and to reduce the allele dropout (ADO). We also employed Sanger sequencing to directly detect the mutation c.1109 C > T in MYOC and NGS-based single nucleotide polymorphism (SNP) haplotyping to distinguish the chromosomes that carried the mutation. Copy number variation (CNV) analysis was carried out to determine the copy number of embryos’ chromosomes. Of the 4 blastocysts obtained in this study, only 2 (sample 5 and 7) could be successfully amplified by WGA. CNV results indicated that chromosomes of both these samples were balanced (46, XN). Sanger sequencing and NGS-based SNP haplotyping confirmed that sample 7 carried the mutation c.1109 C > T in MYOC, while sample 5 did not. Moreover, no ADO was observed. Thus, blastocyst 5 was transferred into the uterus of the patient, and a healthy baby without the MYOC mutation c. 1109C>T was born 39 weeks after transplantation. Our study suggests that NGS-based SNP haplotyping is an effective technique for the PGD of POAG. Abbreviations: PGD: preimplantation genetic diagnosis; POAG: primary open angle glaucoma; NGS: next-generation sequencing; MALBAC: multiple annealing and looping based amplification cycles chemistry; WGA: whole genome amplification; ADO: allele dropout; SNP: single nucleotide polymorphism; CNV: copy number variation; MYOC: Myocilin; OPTN: Optineurin; WDR36: WD repeat domain 36; CYP1B1: Cytochrome P450 1 B Chain; ICSI: intracytoplasmic sperm injection; TFNA: testicular fine-needle aspiration; TE: trophectoderm; PCR: polymerase chain reaction
Application of high-sensitivity flow cytometry in combination with low-voltage scanning electron microscopy for characterization of nanosized objects during platelet concentrate storage

Abstract Platelet concentrates are used in clinic for therapy and prophylaxis of conditions associated with platelet deficiency or malfunction. The characteristics of platelet concentrates gradually change during pretransfusion storage, affecting their clinical effectiveness and the risk of adverse transfusion reactions. The presence of platelet-derived membrane vesicles is an important characteristic of platelet concentrates. Due to their functionality, changes in the number and molecular compositions of platelet-derived vesicles have major effects on the clinical properties of platelet preparations. The existence of different subpopulations of membrane vesicles requires analytical methods capable of providing information at the individual vesicle level. Such methods include flow cytometry and electron microscopy. However, conventional flow cytometry has certain limitations, since the diameters of many platelet-derived membrane vesicles are smaller than its detection limit. The use of classical scanning electron microscopy is also limited due to the requirement for coating with a layer of conductive material, which impedes the detection of small extracellular vesicles. Here, a combination of high-sensitivity flow cytometry and low-voltage scanning electron microscopy was used to increase sensitivity and resolution in the detection of nanosized objects present in platelet concentrates during storage. Apheresis platelet concentrates from eight healthy adult donors were investigated on days 2 and 7 of storage. Fractions of nanosized objects were obtained by differential centrifugation. Fluorophore-conjugated antibodies were used to detect marker-positive vesicles derived from platelets (CD41), red blood cells (CD235a), leukocytes (CD45), and endothelial cells (VEGFR2). Near-spherical objects with diameters ranging from 25 to 700 nm were observed by low-voltage scanning electron microscopy in platelet concentrates and its fractions. On day 7 of storage, objects with diameters of less than 100 nm were attached to and clustered near the terminal ends of pseudopod-like projections. High-sensitivity flow cytometry showed that during storage numbers of CD41(pos) vesicles elevated more than fivefold and numbers of marker-negative nanosized objects, which did not carry any of the investigated cell type-specific markers elevated more than twofold. Major changes in both CD41(pos) vesicles and marker-negative nanosized objects abundances were observed for objects with diameters around 100 nm bead equivalents. Overall, these results emphasized the importance of application of high-sensitivity methods for monitoring the characteristics of cell-derived nanosized objects during platelet concentrate storage.
Using Radiative Convective Equilibrium to Explore Clouds and Climate in the Community Atmosphere Model

Characteristics of, and fundamental differences between, the radiative‐convective equilibrium (RCE) climate states following the Radiative‐Convective Equilibrium Model Intercomparison Project (RCEMIP) protocols in the Community Atmosphere Model version 5 (CAM5) and version 6 (CAM6) are presented. This paper explores the characteristics of clouds, moisture, precipitation and circulation in the RCE state, as well as the tropical response to surface warming, in CAM5 and CAM6 with different parameterizations. Overall, CAM5 simulates higher precipitation rates that result in larger global average precipitation, despite lower outgoing longwave radiation compared to CAM6. Differences in the structure of clouds, particularly the amount and vertical location of cloud liquid, exist between the CAM versions and can, in part, be related to distinct representations of shallow convection and boundary layer processes. Both CAM5 and CAM6 simulate similar peaks in cloud fraction, relative humidity, and cloud ice, linked to the usage of a similar deep convection parameterization. These anvil clouds rise and decrease in extent in response to surface warming. More generally, extreme precipitation, aggregation of convection, and climate sensitivity increase with warming in both CAM5 and CAM6. This analysis provides a benchmark for future studies that explore clouds, convection, and climate in CAM with the RCEMIP protocols now available in the Community Earth System Model. These results are discussed within the context of realistic climate simulations using CAM5 and CAM6, highlighting the usefulness of a hierarchical modeling approach to understanding model and parameterization sensitivities to inform model development efforts.
Is immunoglobulin A nephropathy different in different ethnic populations?

Immunoglobulin A nephropathy (IgAN) is one of the commonest global patterns of primary glomerulonephritis and remains a leading cause of chronic kidney disease and end‐stage renal disease. The sole diagnostic criterion of IgAN remains the presence of dominant mesangial immunoglobulin A deposits on kidney biopsy. Beyond this defining feature, there is significant heterogeneity in the epidemiology, clinical presentation, renal progression and long‐term outcomes of IgAN in different ethnic populations. Mirroring this heterogeneity in clinical phenotypes, there is also marked ethnic variation in the extent of histopathological lesions observed on kidney biopsy, which may partly explain the well‐documented differences in response to immunomodulatory agents reported in different regions of the world. In parallel, disparities have been identified in genetic association studies and key pathogenic pathways in different ethnic populations. Understanding the basis for these differences in IgAN has important implications for both clinical care and future research. In this review, we will examine the impact of ethnicity on the epidemiology, clinical presentation and outcomes, pathogenesis and genetic associations in IgAN.
The Sequence-to-Sequence Architecture with An Embedded Module for Long-Term Traffic Speed Forecasting with Missing Data

Traffic forecasting plays a crucial role in Intelligent Transportation Systems (ITSs), which is proposed to provide traffic status in advance for road users to avoid traffic congestion or other traffic incidents and for authorities to optimise the strategies of traffic management. In this paper, we develop a novel deep learning framework, based on the Sequence-to-Sequence architecture with an embedded module, for long-term traffic speed forecasting with missing data and providing high forecasting accuracy. The embedded module uses Graph Convolution Neural Network for the local spatial dependency analysis by conducting convolutional operation on the k−hop neighbourhood matrix, while utilises Transformer for the global spatial dependency analysis by implementing the attention mechanism that assigns individual weights to neighbour detectors for contributing to the targeted detector. The sequence-to-sequence architecture is built to analyse temporal dependencies of the spatially-fused time series from the embedded module. To evaluate the proposed model against existing well-known ones, the real traffic speed dataset with missing data and frequent traffic incidents is used to train and test the models. The experimental results indicate that our proposed framework achieves the most accuracy forecasting, even obtaining more than 80% accuracy for forecasting two hours in advance.
MicroRNA-145 regulates immune cytokines via targeting FSCN1 in Staphylococcus aureus-induced mastitis in dairy cows.

Dairy cow mastitis is a detrimental factor in milk quality and food safety. Mastitis generally refers to inflammation caused by infection by pathogenic microorganisms. Our studies in recent years have revealed the role of miRNA regulation in Staphylococcus aureus-induced mastitis. In the present study, we overexpressed and suppressed miR-145 to investigate the function of miR-145 in Mac-T cells. Flow cytometry, ELISA and EdU staining were used to detect changes in the secretion of several Mac-T cytokines and in cell proliferation. We found that overexpression of miR-145 in Mac-T cells significantly reduced the secretion of IL-12 and TNF-α, but increased the secretion of IFN-γ; the proliferation of bovine mammary epithelial cells was also inhibited. Using quantitative real-time PCR (qRT-PCR), Western blotting and luciferase multiplex verification techniques, we found that miR-145 targeted and regulated FSCN1. Knock-down of FSCN1 significantly increased the secretion of IL-12, while the secretion of TNF-α was significantly downregulated in Mac-T cells. Upon S. aureus infection of mammary gland tissue, the body initiated inflammatory responses; Bta-miR-145 expression was downregulated, which reduced the inhibitory effect on the FSCN1 gene; and upregulation of FSCN1 expression promoted mammary epithelial cell proliferation to allow the recovery of damaged tissue. The results of the present study will aid in understanding the immune mechanism opposing S. aureus infection in dairy cows and will provide a laboratory research basis for the prevention and treatment of mastitis.
Is there a genuine placebo effect in acute depression treatments? A reassessment of regression to the mean and spontaneous remission

Regression to the mean and spontaneous improvements are rarely considered in interpretations of treatment trials for acute major depression. Here I suggest that regression to the mean and spontaneous remission may account for most improvements seen in placebo groups and also for a large proportion of variance in the acute treatment outcome of both antidepressant pharmacotherapy and psychotherapy. These findings have important implications for the interpretation of active treatments and placebo response in depression trials.
Postoperative Tendon Loading With Treadmill Running Delays Tendon‐to‐Bone Healing: Immunohistochemical Evaluation in a Murine Rotator Cuff Repair Model

Mechanical stress has an important effect on tendon‐to‐bone healing. The purpose of the present study was to compare tendon‐to‐bone healing in animals exposed to either tendon unloading (botulinum toxin injection) or excessive loading (treadmill running) in a murine rotator cuff repair model. Forty‐eight C57BL/6 mice underwent unilateral supraspinatus tendon detachment and repair. Mice in the unloaded group were injected with botulinum toxin to the supraspinatus muscle. The contralateral shoulder of the unloaded group was used as a control. Mice were euthanized at 1, 2, and 4 weeks after surgery and evaluated with hematoxylin–eosin and immunohistochemical (IHC) staining for Ihh, Gli1, Wnt3a, and β‐catenin. The positive staining area on IHC and the Modified Tendon Maturing Score were measured. The score of the unloaded group was significantly higher (better healing) than that of the treadmill group at 4 weeks. Ihh and the glioma‐associated oncogene homolog 1 (Gli1) positive area in the unloaded group were significantly higher than those of the control group at 1 week. The peak time‐points of the Ihh and Gli1 positive area was 1 week for the unloaded group and 2 weeks for the treadmill group. The Wnt3a positive area in the unloaded group was significantly higher than that of the control group at 2 weeks. The β‐catenin positive area in the unloaded group was significantly higher than that of the treadmill group and the control group at 1 week. Our data indicated that the unloaded group has superior tendon maturation compared to the treadmill running group. Excessive tendon loading may delay the tendon healing process by affecting the activity of Ihh and Wnt/β‐Catenin pathways. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1628–1637, 2019.
Mutability of druggable kinases and pro-inflammatory cytokines by their proximity to telomeres and A+T content

Mutations of protein kinases and cytokines are common and can cause cancer and other diseases. However, our understanding of the mutability in these genes remains rudimentary. Therefore, given previously known factors which are associated with high mutation rates, we analyzed how many genes encoding druggable kinases match (i) proximity to telomeres or (ii) high A+T content. We extracted this genomic information using the National Institute of Health Genome Data Viewer. First, among 129 druggable human kinase genes studied, 106 genes satisfied either factors (i) or (ii), resulting in an 82% match. Moreover, a similar 85% match rate was found in 73 genes encoding pro-inflammatory cytokines of multisystem inflammatory syndrome in children. Based on these promising matching rates, we further compared these two factors utilizing 20 de novo mutations of mice exposed to space-like ionizing radiation, in order to determine if these seemingly random mutations were similarly predictable with this strategy. However, only 10 of these 20 murine genetic loci met (i) or (ii), leading to only a 50% match. When compared with the mechanisms of top-selling FDA approved drugs, this data suggests that matching rate analysis on druggable targets is feasible to systematically prioritize the relative mutability—and therefore therapeutic potential—of the novel candidates.
Incidence and features of thrombosis in children with inherited antithrombin deficiency

Pediatric thromboembolism (≤18 years) is very rare (0.07-0.14/10,000/year) but may be more prevalent in children with severe thrombophilia (protein C, protein S or antithrombin deficiency). The aim of this study was to define the prevalence and clinical characteristics of pediatric thrombosis in subjects with inherited antithrombin deficiency. Our observational retrospective multicentric study from two countries recruited 968 patients of any age from 441 unrelated families with genetically, biochemically and functionally characterized antithrombin deficiency. Seventy-three subjects (7.5%) developed thrombosis before 19 years of age. Two high-risk periods for thrombosis were identified: adolescence (12-18 years, n=49) with thrombus localization (lower limb deep venous thrombosis or pulmonary embolism) and triggering factors common to adults (oral contraceptives, surgery or pregnancy); and the neonatal period (<30 days, n=15) with idiopathic thrombosis at unusual sites. The clinical evaluation of pediatric thrombosis in subjects with antithrombin deficiency revealed: i) a high prevalence of cerebral sinovenous thrombosis (n=13, 17.8%), mainly at young age (8 neonates and 4 children <6 years); ii) severe outcome with fatality in six cases (3 neonates, two of them homozygous for p.Leu131Phe). The majority of subjects (76.7%) carried quantitative type I deficiency. This retrospective analysis includes the largest cohort of subjects with inherited antithrombin deficiency so far and provides strong evidence for an increased risk of pediatric thrombosis associated with this thrombophilia (300-fold compared with the general population: 0.41%/year vs. 0.0014%/year, respectively). Our results support testing for antithrombin deficiency in children of affected families, particularly in case of type I deficiency.
Atypical Presentations of Acute Infections in Hospitalized Older Adults: The Prevalence, Predictors, and Outcomes

Background Older adults are at increased risk of infection, which is a leading cause of morbidity and mortality in this age group. [1] The increased infections related mortality in elderly is attributed to multiple factors, including: immunosenescence, medical comorbidities, undernutrition, functional decline, frailty, and increased adverse drug events [2] . Reaching a final disease-specific diagnosis, remains a clinical dilemma when managing older adults. According to Fried et al., less than half of the elderly patients fitted into the classical medical model where the presenting symptoms and signs can refer immediately to a certain disease. [3] In the aged, Infections often have atypical presentations which may complicate and delay diagnosis. The most frequently encountered atypical presentations of infections include delirium, anorexia, functional impairment, falls, fatigue, and new or worsening urinary incontinence. [4,5]
Trends in Emergency Department Use by Rural and Urban Populations in the United States

Key Points Question How do payer status and patient demographic characteristics differ between urban and rural emergency department (ED) visits? Findings In this cross-sectional study of National Hospital Ambulatory Medical Care Survey data, rural ED visit rates increased by more than 50%, from 36.5 to 64.5 per 100 persons, outpacing urban ED visit rates, which increased from 40.2 to 42.8 visits per 100 persons. Rural ED use increased for those aged 18 to 64 years, non-Hispanic white patients, Medicaid beneficiaries, and patients without insurance, with a larger proportion of rural EDs categorized as safety-net EDs. Meaning Rural EDs experienced greater growth in ED use simultaneous with increased pressure as safety-net hospitals.
Treatment of liver and spleen illnesses by herbs: Recommendations of Avicenna’s heritage "Canon of Medicine"

Objective: Avicenna (Abu Ali al-Hossein ibn Abdullah ibn Sina) who had a special attention toward diseases treatments, gathered results of ages of herbal medicine experiments on humans and animals in his book “Al-Qānūn fī Ṭibb” or "The Canon of Medicine", which is a reliable book in Iranian traditional medicine. The aim of this research was to build a reliable list of plants effective against liver and spleen diseases, based on Avicenna's book (volume 2). Materials and Methods: By studying the monographs, introduced agents that have been effective in liver and spleen diseases were identified. Upon their origin and effectiveness in diseases of the liver, spleen or both, treatments were organized. Results: From a huge number of drugs, 163 plants from 73 families were found to be effective in treatment of liver and spleen illnesses. In addition, 30 non-herbal agents effective in treatment of liver diseases were detected. The Lamiaceae family have the most effective herbs for treatment of diseases of the liver, spleen or both. Hemp Agrimony, Irsā, and Fūdhanj achieved the highest scores. Conclusion: The effects of different plants on liver and spleen diseases were indicated in Avicenna's book. Due to the report on the above book, further studies needed specially on the effect of Irsā (Iris ensata) and family Lamiaceae on liver and spleen diseases.
Self-efficacy, beliefs, and goals: Moderation of declining physical activity during adolescence.

OBJECTIVE To examine whether the decline in physical activity observed from childhood through adolescence is explained by moderating effects of self-efficacy on concurrent changes in children's goals and beliefs about their physical activity environments. METHOD Latent growth modeling was used in longitudinal tests in a cohort of 79 boys and 108 girls assessed in 5th, 6th, 7th, 9th, and 11th grades. RESULTS Physical activity measured objectively by an accelerometer declined most in students who had bigger declines in self-efficacy and (1) maintained higher perceptions of barriers to physical activity, (2) had bigger declines in enjoyment and fitness goals, or (3) had smaller declines in appearance and social goals. CONCLUSIONS Trials of physical activity interventions based on social-cognitive theory should consider that the influence of changing goals on physical activity may differ according to whether students maintain high efficacy beliefs about overcoming barriers to physical activity coincident with perceptions of their physical activity environment. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Seasonal and Solar Cycle Dependence of Energy Transfer Rates in the Auroral E‐Region

We report one of the first comprehensive ground‐based investigations of energy transfer rates in the E‐region ionosphere compared relative to geomagnetic activity, seasonal effects, and solar activity level using nearly continuously sampled data collected with the Poker Flat Incoherent Scatter Radar (PFISR) between 2010 and 2019. We quantified the integrated electromagnetic (EM) energy transfer rate and the integrated Joule heating rate in the E‐region between 90 and 130 km, which includes the contribution from the neutral winds. We find that (a) the median Joule heating rate and EM energy transfer rate in the evening sector are larger in the winter versus the summer and have similar magnitudes in the spring and fall for the same solar activity and geomagnetic conditions. (b) The seasonal dependence of the energy transfer rates is closely associated with the seasonal variations of the electric fields. Our analysis shows that the larger EM energy transfer and Joule heating rates in disturbed conditions in the winter versus the summer are associated with the combined effects of both the electric field and Pedersen conductance with the electric field playing a dominant role. Given that the Pedersen conductance in the evening sector is closely related to the particle precipitation and field aligned currents in the auroral region, this study provides complementary ionospheric evidence of the winter‐summer asymmetry of the intensity and density of field‐aligned currents (e.g., Ohtani et al., 2009, https://doi.org/10.1029/2009ja014115). (c) The geomagnetic activity level has the most significant impact on the magnitude of the energy transfer rates, followed by seasonal variations, and last the solar activity level.