Miracle-dz/UniFAR-FTUs huggingface dataset:
Brain microstructural and metabolic alterations detected in vivo at onset of the first demyelinating event

Abstract In early multiple sclerosis, a clearer understanding of normal-brain tissue microstructural and metabolic abnormalities will provide valuable insights into its pathophysiology. We used multi-parametric quantitative MRI to detect alterations in brain tissues of patients with their first demyelinating episode. We acquired neurite orientation dispersion and density imaging [to investigate morphology of neurites (dendrites and axons)] and 23Na MRI (to estimate total sodium concentration, a reflection of underlying changes in metabolic function). In this cross-sectional study, we enrolled 42 patients diagnosed with clinically isolated syndrome or multiple sclerosis within 3 months of their first demyelinating event and 16 healthy controls. Physical and cognitive scales were assessed. At 3 T, we acquired brain and spinal cord structural scans, and neurite orientation dispersion and density imaging. Thirty-two patients and 13 healthy controls also underwent brain 23Na MRI. We measured neurite density and orientation dispersion indices and total sodium concentration in brain normal-appearing white matter, white matter lesions, and grey matter. We used linear regression models (adjusting for brain parenchymal fraction and lesion load) and Spearman correlation tests (significance level P ≤ 0.01). Patients showed higher orientation dispersion index in normal-appearing white matter, including the corpus callosum, where they also showed lower neurite density index and higher total sodium concentration, compared with healthy controls. In grey matter, compared with healthy controls, patients demonstrated: lower orientation dispersion index in frontal, parietal and temporal cortices; lower neurite density index in parietal, temporal and occipital cortices; and higher total sodium concentration in limbic and frontal cortices. Brain volumes did not differ between patients and controls. In patients, higher orientation dispersion index in corpus callosum was associated with worse performance on timed walk test (P = 0.009, B = 0.01, 99% confidence interval = 0.0001 to 0.02), independent of brain and lesion volumes. Higher total sodium concentration in left frontal middle gyrus was associated with higher disability on Expanded Disability Status Scale (rs = 0.5, P = 0.005). Increased axonal dispersion was found in normal-appearing white matter, particularly corpus callosum, where there was also axonal degeneration and total sodium accumulation. The association between increased axonal dispersion in the corpus callosum and worse walking performance implies that morphological and metabolic alterations in this structure could mechanistically contribute to disability in multiple sclerosis. As brain volumes were neither altered nor related to disability in patients, our findings suggest that these two advanced MRI techniques are more sensitive at detecting clinically relevant pathology in early multiple sclerosis.
Self-collected and clinician-collected anal swabs show modest agreement for HPV genotyping

Background & aim Women with HIV/HPV coinfection and cervical lesions are at increased risk of developing HPV related anal cancer. Self-collection of anal swabs may facilitate HPV molecular testing in anal cancer screening, especially in high-risk groups, and yet it is not adequately studied. We evaluated level of agreement between self-collected anal swabs (SCAS) and clinician-collected anal swabs (CCAS) when used for HPV genotyping. We also described the anal HPV genotype distribution and HIV/HPV coinfection. Methods We performed a cross sectional study with participants from a visual-inspection-with-acetic-acid and cervicography (VIAC) clinic, in Harare, Zimbabwe. In a clinic setting, the women aged ≥18 years provided anal swabs in duplicate; first CCAS and then SCAS immediately after. HPV detection and genotyping were performed using next generation amplicon sequencing of a 450bp region of the HPV L1 gene. Level of agreement of HPV genotypes between CCAS and SCAS was calculated using the kappa statistic. McNemar tests were used to evaluate agreement in the proportion of genotypes detected by either method. Results Three-hundred women provided 600 samples for HPV genotyping. HPV genotypes were detected in 25% of SCAS and in 22% of CCAS. The most common genotypes with CCAS were HPV52, HPV62 and HPV70 and with SCAS were HPV62, HPV44, HPV52, HPV53 and HPV68. Total HPV genotypes detected in CCAS were more than those detected in SCAS, 32 versus 27. The agreement of HPV genotypes between the two methods was 0.55 in kappa value (k). The test of proportions using McNemar gave a Chi-square value of 0.75 (p = 0.39). Multiple HPV infections were detected in 28/75 and 29/67 women for CCAS and SCAS respectively. Conclusions SCAS and CCAS anal swabs showed moderate agreement, with no statistically significant difference in the proportion of genotypes detected by either methods. Although the differences between the two methods were not statistically significant, CCAS detected more HPV genotypes than SCAS and more HPV infections were detected in SCAS than in CCAS. Our data suggest that self-collected anal swabs can be used as an alternative to clinician-collected anal swabs for HPV genotyping.
Disparities in Kidney Stone Disease: A Scoping Review

Purpose: We reviewed the available evidence regarding health disparities in kidney stone disease to identify knowledge gaps in this area. Materials and Methods: A literature search was conducted using PubMed®, Embase® and Scopus® limited to articles published in English from 1971 to 2020. Articles were selected based on their relevance to disparities in kidney stone disease among adults in the United States. Results: Several large epidemiological studies suggest disproportionate increases in incidence and prevalence of kidney stone disease among women as well as Black and Hispanic individuals in the United States, whereas other studies of comparable size do not report racial and ethnic demographics. Numerous articles describe disparities in imaging utilization, metabolic workup completion, analgesia, surgical intervention, stone burden at presentation, surgical complications, followup, and quality of life based on race, ethnicity, socioeconomic status and place of residence. Differences in urinary parameters based on race, ethnicity and socioeconomic status may be explained by both dietary and physiological factors. All articles assessed had substantial risk of selection bias and confounding. Conclusions: Health disparities are present in many aspects of kidney stone disease. Further research should focus not only on characterization of these disparities but also on interventions to reduce or eliminate them.
The impact of the COVID-19 pandemic on application of European Society of Cardiology (ESC) guidelines for exercise in adults with CHD: a data-based questionnaire

Abstract Introduction: Regular physical activity is safe and effective therapy for adults with CHD and is recommended by European Society of Cardiology guidelines. The COVID-19 pandemic poses enormous challenges to healthcare teams and patients when ensuring guideline compliance. We explored the implications of COVID-19 on physical activity levels in adult CHD patients. Materials and methods: A data-based questionnaire was distributed to adult CHD patients at a regional tertiary centre from October to November 2020. Results: Prior to the COVID-19 pandemic, 96 (79.3%) of 125 respondents reported participating in regular physical activity, with 66 (52.8%) meeting target levels (moderate physical activity for at least 150 minutes per week). Commonest motivations for physical activity were general fitness (53.6%), weight loss (36.0%), and mental health benefits (30.4%). During the pandemic, the proportion that met target levels significantly decreased from 52.8% to 40.8% (p = 0.03). The commonest reason was fear of COVID-19 (28.0%), followed by loss of motivation (23.2%) and gym/fitness centre closure (15.2%). Discussion: The COVID-19 pandemic has negatively impacted exercise levels of adult CHD patients. Most do not meet recommended physical activity levels, mainly attributable to fear of COVID-19. Even before the pandemic, only half of respondents met physical activity guidelines. Availability of online classes can positively impact exercise levels so could enhance guideline compliance. This insight into health perceptions and behaviours of adult CHD patients may help develop quality improvement initiatives to improve physical activity levels in this population.
Long noncoding RNA DLGAP1-AS1 promotes the progression of glioma by regulating the miR-1297/EZH2 axis

Dysregulated lncRNAs have been implicated in a plethora of tumors, including glioma. One such oncogenic lncRNAs that has been reported in several cancers is the lncRNA DLGAP1 antisense RNA 1 (DLGAP1-AS1). This study seeks to characterize the expression of DLGAP1-AS1 in glioma tissues, which we found to be raised in both glioma samples and cell lines. Functional experiments revealed that DLGAP1-AS1 promoted in vitro glioma cell invasion, migration and proliferation. DLGAP1-AS1 was found to function as a miR-1297 sponge, based on information from luciferase reporter assays, RNA pull-down assays and publicly available online databases. miR-1297 was in turn found to functionally target EZH2. DLGAP1-AS1 modulated EZH2 expressions through miR-1297 sponging. Glioma progression appears to be supported DLGAP1-AS1 -promoted activation of the miR-1297/EZH2 axis. The components of this axis may function as therapeutic targets for glioma.
Effect of different final irrigation protocols on pulp tissue dissolution from an isthmus model.

This study assessed the pulp tissue dissolution from isthmus of a two-rooted maxillary premolar using different final irrigation protocols. After root canal preparation, the surface of the tooth was reduced to an extent that the isthmus could be observed, and 1 mg of pulp tissue was introduced into the isthmus which was covered with a glass slide. Following six groups were tested: syringe and needle; subsonic activation; sonic activation; ultrasonic activation; heating followed by sonic activation; and heating followed by ultrasonic activation. Before and after each experiment a photograph of the isthmus was taken at 30× to register the area of the pulp tissue. Statistical analysis was performed with Kruskal-Wallis and Mann-Whitney tests (P < 0.05). Syringe and needle group showed the lower value of pulp tissue dissolution followed by subsonic irrigation procedures. Pulp tissue dissolution was significantly higher when heating was followed by sonic or ultrasonic activation.
Micro-size plankton abundance and assemblages in the western North Pacific Subtropical Gyre under microscopic observation

While primary productivity in the oligotrophic North Pacific Subtropical Gyre (NPSG) is changing, the micro-size plankton community has not been evaluated in the last 4 decades, prompting a re-evaluation. We collected samples over three years (2016–2018) from depths of 10 to 200 m (n = 127), and the micro-size plankton were identified and counted to understand the heterogeneity of micro-size plankton community structure. The assemblages were consistent to the those of 4 decades ago. Dinophyceae (dinoflagellates) were the most numerically abundant, followed by Cryptophyceae and Bacillariophyceae (diatoms). The other micro-size plankton classes (Cyanophyceae, Haptophyceae, Dictyochophyceae, Euglenophyceae, and Prasinophyceae) were not always detected, whereas only Trichodesmium spp. was counted in the Cyanophyceae. Other unidentified autotrophic and heterotrophic flagellates were also significantly present, and their numeric abundance was higher than or at the same level as was that of the Dinophyceae. In the Dinophyceae, Gymnodiniaceae and Peridiniales were abundant. The chlorophyll a concentration and these class-level assemblages suggested micro-size plankton is not a major primary producer in this area. We applied generalized additive models (GAMs) and principal coordination analyses (PCoAs) to evaluate the habitats of every plankton group and the heterogeneity of the assemblages. The GAMs suggested that every classified plankton abundance showed a similar response to salinity, and we observed differences in habitats in terms of temperature and nitrate concentrations. Based on the PCoAs, we observed unique communities at the 200 m depth layer compared with those at the other sampling layers. The site scores of PCoAs indicated that the micro-size plankton assemblages are most heterogeneous at the 10 m depth layer. At such depth, diazotrophic Cyanophyceae (Trichodesmium spp.) are abundant, particularly in less-saline water. Therefore, nitrogen fixation may contribute to the heterogeneity in the abundance and assemblages in the western NPSG.
Distinct Response to Platinum-Based Chemotherapy among Patients with Metastatic Castration-Resistant Prostate Cancer Harboring Alterations in Genes Involved in Homologous Recombination

Purpose: We aimed to explore the association between genomic status and clinical outcome of platinum-based chemotherapy among patients with metastatic castration-resistant prostate cancer (mCRPC). Materials and Methods: We conducted a retrospective study of 55 patients with mCRPC who received platinum-based chemotherapy after the progression to docetaxel chemotherapy and underwent genomic profiling of 14 homologous recombination (HR) pathway genes. Progression-free survival (PFS) was analyzed using the Kaplan-Meier method. Results: Of 55 patients, 23 harbored genomic defects in HR pathway genes. Median prostate specific antigen (PSA)-PFS for the HR defect group was 6.7 months compared with 2.6 months for the no HR defect group (p=0.001). The patients harboring somatic HR defect displayed shorter PSA-PFS than those harboring germline HR defect (4.5 months vs not available; p=0.066). The PSA50 (patients who survived for 12 weeks and had a PSA decline over 50% from baseline) response rate displayed higher in patients harboring BRCA2 or ATM defect (6/8, 75.0%) than in those harboring CDK12 defect (2/9, 22.2%; p=0.06). Patients harboring BRCA2 or ATM defect displayed prolonged PSA-PFS, compared with those harboring CDK12 defect and those harboring other HR defect (p=0.038). In multivariate Cox regression analysis, HR defect and BRCA2 or ATM defect were independent significant factors associated with superior PAS-PFS to platinum-based chemotherapy. Conclusions: The patients with mCRPC harboring alterations in different HR genes displayed distinct response to platinum-based chemotherapy. Patients with mCRPC harboring genomic defects in crucial HR genes either in the germline or somatic, especially BRCA2 and ATM, might experience superior outcomes to platinum-based chemotherapy, compared with those harboring CDK12 defect.
Dynamic decorrelation as a unifying principle for explaining a broad range of brightness phenomena

The visual system is highly sensitive to spatial context for encoding luminance patterns. Context sensitivity inspired the proposal of many neural mechanisms for explaining the perception of luminance (brightness). Here we propose a novel computational model for estimating the brightness of many visual illusions. We hypothesize that many aspects of brightness can be explained by a dynamic filtering process that reduces the redundancy in edge representations on the one hand, while non-redundant activity is enhanced on the other. The dynamic filter is learned for each input image and implements context sensitivity. Dynamic filtering is applied to the responses of (model) complex cells in order to build a gain control map. The gain control map then acts on simple cell responses before they are used to create a brightness map via activity propagation. Our approach is successful in predicting many challenging visual illusions, including contrast effects, assimilation, and reverse contrast with the same set of model parameters.
Benefit versus risk of chromosomal microarray analysis performed in pregnancies with normal and positive prenatal screening results: A retrospective study

Background Most studies on chromosomal microarray analysis (CMA) and amniocentesis risks have not evaluated pregnancies with low risk for genetic diseases; therefore, the efficacy and safety of CMA and amniocentesis in this population are unclear. This study aimed to examine the benefits and risks of prenatal genetic diagnostic tests in pregnancies having low risk for chromosomal diseases. Methods and findings In this retrospective study, we used clinical data from a large database of 30,830 singleton pregnancies at gestational age 16–23 weeks who underwent amniocentesis for karyotyping with or without CMA. We collected socio-demographic, medical and obstetric information, along with prenatal screening, CMA and karyotyping results. Fetal loss events were also analysed. CMA was performed in 5,837 pregnancies with normal karyotype (CMA cohort). In this cohort, 4,174 women had normal prenatal screening results and the risk for identifying genetic abnormalities with >10% risk for intellectual disability by CMA was 1:102, with no significant difference between maternal age groups. The overall post-amniocentesis fetal loss rate was 1:1,401 for the entire cohort (n = 30,830) and 1:1,945 for the CMA cohort (n = 5,837). The main limitation of this study is the relatively short follow-up of 3 weeks, which may not have been sufficient for detecting all fetal loss events. Conclusion The low risk for post-amniocentesis fetal loss, compared to the rate of severe genetic abnormalities detected by CMA, suggests that even pregnant women with normal prenatal screening results should consider amniocentesis with CMA.
Incidence, risk factors, clinical characteristics and outcomes of deep venous thrombosis in patients with COVID-19 attending the Emergency Department: results of the UMC-19-S8

Background and importance A higher incidence of venous thromboembolism [both pulmonary embolism and deep vein thrombosis (DVT)] in patients with coronavirus disease 2019 (COVID-19) has been described. But little is known about the true frequency of DVT in patients who attend emergency department (ED) and are diagnosed with COVID-19. Objective We investigated the incidence, risk factors, clinical characteristics and outcomes of DVT in patients with COVID-19 attending the ED before hospitalization. Methods We retrospectively reviewed all COVID patients diagnosed with DVT in 62 Spanish EDs (20% of Spanish EDs, case group) during the first 2 months of the COVID-19 outbreak. We compared DVT-COVID-19 patients with COVID-19 without DVT patients (control group). Relative frequencies of DVT were estimated in COVID and non-COVID patients visiting the ED and annual standardized incidences were estimated for both populations. Sixty-three patient characteristics and four outcomes were compared between cases and controls. Results We identified 112 DVT in 74 814 patients with COVID-19 attending the ED [1.50‰; 95% confidence interval (CI), 1.23–1.80‰]. This relative frequency was similar than that observed in non-COVID patients [2109/1 388 879; 1.52‰; 95% CI, 1.45–1.69‰; odds ratio (OR) = 0.98 [0.82-1.19]. Standardized incidence of DVT was higher in COVID patients (98,38 versus 42,93/100,000/year; OR, 2.20; 95% CI, 2.03–2.38). In COVID patients, the clinical characteristics associated with a higher risk of presenting DVT were older age and having a history of venous thromboembolism, recent surgery/immobilization and hypertension; chest pain and desaturation at ED arrival and some analytical disturbances were also more frequently seen, d-dimer >5000 ng/mL being the strongest. After adjustment for age and sex, hospitalization, ICU admission and prolonged hospitalization were more frequent in cases than controls, whereas mortality was similar (OR, 1.37; 95% CI, 0.77–2.45). Conclusions DVT was an unusual form of COVID presentation in COVID patients but was associated with a worse prognosis.
Causal Effect of MMP-1 (Matrix Metalloproteinase-1), MMP-8, and MMP-12 Levels on Ischemic Stroke

Supplemental Digital Content is available in the text. Background and Purpose: MMP (matrix metalloproteinase) levels have been widely associated with ischemic stroke risk and poststroke outcome. However, their role as a risk factor or as a subeffect because of ischemia is uncertain. Methods: We performed a literature search of genome-wide studies that evaluate serum/plasma levels of MMPs. We used a 2-sample Mendelian randomization approach to evaluate the causality of MMP levels on ischemic stroke risk or poststroke outcome, using 2 cohorts: MEGASTROKE (n=440 328) and GODs (n=1791). Results: Genome-wide association studies of MMP-1, MMP-8, and MMP-12 plasma/serum levels were evaluated. A significant association, which was also robust in the sensitivity analysis, was found with all ischemic strokes: MMP-12 (odds ratio=0.90 [95% CI, 0.86–0.94]; q value=7.43×10−5), and with subtypes of stroke, large-artery atherosclerosis: MMP-1 (odds ratio=0.95 [95% CI, 0.92–0.98]; q value=0.01) and MMP-12 (odds ratio=0.71 [95% CI, 0.65–0.77]; q value=5.11×10−14); small-vessel occlusion: MMP-8 (odds ratio=1.24 [95% CI, 1.06–1.45]; q value=0.03). No associations were found in relation to stroke outcome. Conclusions: Our study suggests a causal link between lower serum levels of MMP-12 and the risk of ischemic stroke, lower serum levels of MMP-1 and MMP-12 and the risk of large-artery stroke and higher serum levels of MMP-8 and the risk of lacunar stroke.
Time-course transcriptomic analysis of Petunia ×hybrida leaves under water deficit stress using RNA sequencing

Water deficit limits plant growth and development, resulting in quality loss of horticultural crops. However, there is limited information on gene regulation and signaling pathways related to water deficit stress response at multiple time points. The objective of this research was to investigate global gene expression patterns under water deficit stress to provide an insight into how petunia (Petunia ×hybrida ‘Mitchell Diploid’) responded in the process of stress. Nine-week-old petunias were irrigated daily or placed under water stress by withholding water. Stressed plants reduced stomatal conductance after five days of water deficit, indicating they perceived stress and initiated stress response mechanisms. To analyze transcriptomic changes at the early stage of water deficit, leaf tissue samples were collected 1, 3, and 5 days after water was withheld for RNA sequencing. Under water deficit stress, 154, 3611, and 980 genes were upregulated and 41, 2806, and 253 genes were downregulated on day 1, 3, and 5, respectively. Gene Ontology analysis revealed that redox homeostasis processes through sulfur and glutathione metabolism pathways, and hormone signal transduction, especially abscisic acid and ethylene, were enriched under water deficit stress. Thirty-four transcription factor families were identified, including members of AP2/ERF, NAC, MYB-related, C2H2, and bZIP families, and TFs in AP2/ERF family was the most abundant in petunia. Interestingly, only one member of GRFs was upregulated on day 1, while most of TFs were differentially expressed on day 3 and/or 5. The transcriptome data from this research will provide valuable molecular resources for understanding the early stages of water stress-responsive networks as well as engineering petunia with enhanced water stress tolerance.