Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinico-mycological analysis and antifungal resistance pattern in human immunodeficiency virus-associated candidiasis: An Indian perspective

Objectives: Candidiasis is a common human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome-associated opportunistic mycoses. The present study ascertained the species spectrum of Candida strains recovered from different clinical samples from symptomatic HIV-positive individuals and determined the antifungal susceptibility profile of the isolates. Materials and Methods: A variety of specimens were collected from 234 symptomatic HIV seropositive individuals depending on their clinical manifestations and subjected to direct microscopic examination. Blood samples were inoculated in biphasic blood culture medium and all other specimens on Sabouraud dextrose agar with chloramphenicol and incubated at 35°C–37°C. Species identification of the recovered Candida isolates was attempted on the basis of germ tube production, micromorphology on corn meal agar, color and morphology on HiCrome Candida Differential agar, and carbohydrate fermentation and assimilation tests. Susceptibility testing of the isolates was performed employing the VITEK 2 system. Results: A total of 167 Candida isolates were obtained; Candida albicans (136), Candida tropicalis (13), Candida krusei (8), Candida parapsilosis (5), Candida glabrata (4), and Candida kefyr (1). Fluconazole resistance was more frequent among nonalbicans species, and significantly higher 5-fluorocytosine resistance compared to C. albicans was also observed. Eight Candida strains (six C. krusei, one C. kefyr, and one C. albicans) were multidrug resistant. Conclusion: Although C. albicans continues to be the leading etiological agent of candidiasis, the incidence of nonalbicans species among HIV-positive Indian individuals is rising. Antifungal resistance was higher among nonalbicans Candida species. Another issue of therapeutic concern is the possible emergence of multidrug-resistant Candida strains among these patients.
Direct binding of Cdt2 to PCNA is important for targeting the CRL4Cdt2 E3 ligase activity to Cdt1

The C-terminal end of Cdt2 contains a PIP box for binding to PCNA to promote CRL4Cdt2 function, creating a new paradigm where the substrate receptor and substrates bind to a common multivalent docking platform for ubiquitination. The CRL4Cdt2 ubiquitin ligase complex is an essential regulator of cell-cycle progression and genome stability, ubiquitinating substrates such as p21, Set8, and Cdt1, via a display of substrate degrons on proliferating cell nuclear antigens (PCNAs). Here, we examine the hierarchy of the ligase and substrate recruitment kinetics onto PCNA at sites of DNA replication. We demonstrate that the C-terminal end of Cdt2 bears a PCNA interaction protein motif (PIP box, Cdt2PIP), which is necessary and sufficient for the binding of Cdt2 to PCNA. Cdt2PIP binds PCNA directly with high affinity, two orders of magnitude tighter than the PIP box of Cdt1. X-ray crystallographic structures of PCNA bound to Cdt2PIP and Cdt1PIP show that the peptides occupy all three binding sites of the trimeric PCNA ring. Mutating Cdt2PIP weakens the interaction with PCNA, rendering CRL4Cdt2 less effective in Cdt1 ubiquitination and leading to defects in Cdt1 degradation. The molecular mechanism we present suggests a new paradigm for bringing substrates to the CRL4-type ligase, where the substrate receptor and substrates bind to a common multivalent docking platform to enable subsequent ubiquitination.
A taxonomic summary and revision of Rozella (Cryptomycota)

Rozella is a genus of endoparasites of a broad range of hosts. Most species are known by their morphology and host specificity, while only three have been examined ultrastructurally and had portions of their genome sequenced. Determined in molecular phylogenies to be the earliest diverging lineage in kingdom Fungi, Rozella currently nests among an abundance of environmental sequences in phylum Cryptomycota, superphylum Opisthosporidia. Here we briefly summarize a history of Rozella, provide descriptions of all species, and include a key to the species of Rozella.
Non-inferior low-dose coronary computed tomography angiography image quality with knowledge-based iterative model reconstruction for overweight patients

We investigated the feasibility of low-dose coronary computed tomography angiography (CCTA), using a prospective electrocardiogram (ECG)-triggered axial scan protocol, knowledge-based iterative model reconstruction (IMR), and fixed tube current, in overweight subjects. Forty non-overweight (group A; body-mass index [BMI] < 25 kg/m2) and 40 overweight individuals (group B; BMI = 25–30 kg/m2), who underwent CCTA for coronary artery disease screening, were retrospectively and consecutively enrolled. A 64-slice CT scanner was used at 100-kVp tube voltage and 150-mA tube current, and images were reconstructed using IMR techniques. Image noise, attenuation at the aorta, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) at the proximal right and left main coronary arteries (pRCA and LMCA) were calculated. CCTA images were qualitatively evaluated using a four-point scale (1, poor; 4, excellent) and analyzed using a non-inferiority test with a pre-defined non-inferiority margin of -0.2. The mean CCTA radiation dose (Group A: 1.33 ± 0.02 mSv; Group B: 1.35 ± 0.10 mSv; p = 0.151) and mean aortic root CT attenuation values (Group A: 447.9 ± 81.6 HU; Group B: 439.5 ± 63.6 HU; p = 0.571) did not differ significantly between the two groups. The mean noise in groups A and B was 26.0 ± 4.8 HU and 29.2 ± 4.4 HU, respectively (p = 0.005). The noise reduction ratio in the groups, compared to filtered back projection, was 65.0% and 68.1%, respectively. The mean grade of image quality did not differ significantly (3.75 ± 0.04 vs. 3.71 ± 0.04, p = 0.478). Group B CCTA image quality was non-inferior (mean difference = -0.043, 95% CI = -0.162–0.077) to that of Group A. We concluded that low-dose CCTA with prospective ECG-triggering and IMR might be applied to overweight subjects, as well as to normal-weight subjects, by using a fixed tube current without an increase in tube current based on the patient’s body size.
Effects of Valproate Monotherapy on the Oxidant-Antioxidant Status in Mexican Epileptic Children: A Longitudinal Study

Epilepsy is a neurological disorder that can produce brain injury and neuronal death. Several factors such as oxidative stress have been implicated in epileptogenesis. Valproic acid (VPA) is a widely used drug for the treatment of epilepsy, but the mechanisms underlying these benefits are complex and still not fully understood. The objective of this study was to evaluate, for the first time, the effects of VPA on the oxidant-antioxidant status in Mexican epileptic children before and after 6 or 12 months of treatment with VPA by determining the activities of several plasmatic antioxidant enzymes (glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT)) and oxidant marker (malondialdehyde (MDA), hydrogen peroxide (H2O2), 8-hydroxy-2-deoxyguanosine (8-OHdG), and 3-nitrotyrosine (3-NT) levels) profiles. The possible relationships between these markers and some clinicopathological factors were also evaluated. Plasma samples were obtained from the peripheral blood of 16 healthy children and 32 patients diagnosed with epilepsy, and antioxidant/oxidant markers were measured spectrometrically. Significant decreases in all antioxidant enzyme activities, with the exception of GPx, and increases in all oxidant markers in epileptic subjects versus healthy children were observed. Interestingly, all these effects reverted after VPA monotherapy, although the results were different depending on the treatment period (6 or 12 months). These changes were contingent upon brain imaging findings, type of epilepsy, etiology of epilepsy, and the efficacy of 6 months of VPA monotherapy. Significant and positive correlations of GPx and SOD activities and H2O2 and 8-OHdG levels with the age of children at the beginning of treatment were observed. H2O2 levels were also positively correlated with number of seizures before VPA monotherapy. VPA showed significant antioxidant effects decreasing seizure activity, possibly depending on the presence of cerebral structural alterations, treatment time, and age.
The Association of Radial Artery Pulse Wave Variables with the Pulse Wave Velocity and Echocardiographic Parameters in Hypertension

This study aims at exploring the cardiovascular pathophysiological mechanism of TCM (traditional Chinese medicine) pulse by detecting the correlation between radial artery pulse wave variables and pulse wave velocity/echocardiographic parameters. Two hundred Chinese subjects were enrolled in this study, which were grouped into health control group, hypertension group, and hypertensive heart disease group. Physical data obtained in this study contained TCM pulse images at “Guan” position of the left hand, pulse wave velocity, and echocardiographic parameters. Linear and stepwise regression analysis was performed to assess the association of radial artery pulse wave variables with pulse wave velocity and echocardiographic parameters in the total population and in each different group. After adjusting for related confounding factors, decrease of t1, t5 and increase of h1, h3/h1 were statistically associated with arterial stiffness in the total population (P<0.05). Moreover, the correlation study in each group showed that the decrease of both t3 and h5 was also related to arterial stiffness (P<0.05). In terms of echocardiographic parameters, the height of dicrotic wave indicated by h5 was the most relevant pulse wave variable. For the health control, h5 was negatively associated with interventricular septal thickness (VST) and left ventricular posterior wall thickness (PWT) (P<0.05), while for the hypertension population and those with target-organ damage to heart, increase of h5 might be associated with decrease of ejection fraction (EF) and increase of all the remaining echocardiographic parameters especially for left ventricular end-systolic diameter (LVDs) and Left ventricular end-diastolic diameter (LVDd) (P<0.05). In conclusion, we found radial artery pulse wave variables were in association with the arterial stiffness and echocardiographic changes in hypertension, which would provide an experimental basis for cardiovascular pathophysiological mechanism of radial artery pulse wave variables.
The development of a decellularized extracellular matrix–based biomaterial scaffold derived from human foreskin for the purpose of foreskin reconstruction in circumcised males

The circumcision of males is emphatically linked to numerous sexual dysfunctions. Many of the purported benefits do not hold up to the scrutiny of extensive literature surveys. Involuntary circumcision, particularly when not medically warranted, is also associated with many psychological and emotional traumas. Current methods to reconstruct the ablated tissue have significant drawbacks and produce a simple substitute that merely imitates the natural foreskin. Extracellular matrix–based scaffolds have been shown to be highly effective in the repair and regeneration of soft tissues; however, due to the unique nature of the foreskin tissue, commercially available biomaterial scaffolds would yield poor results. Therefore, this study discusses the development and evaluation of a tissue engineering scaffold derived from decellularized human foreskin extracellular matrix for foreskin reconstruction. A chemicophysical decellularization method was applied to human foreskin samples, sourced from consenting adult donors. The resulting foreskin dermal matrices were analyzed for their suitability for tissue engineering purposes, by biological, histological, and mechanical assessment; fresh frozen foreskin was used as a negative control. Sterility of samples at all stages was ensured by microbiological analysis. MTT assay was used to evaluate the absence of viable cells, and histological analysis was used to confirm the maintenance of the extracellular matrix structure and presence/integrity of collagen fibers. Bioactivity was determined by submitting tissue extracts to enzyme-linked immunosorbent assay and quantifying basic fibroblast growth factor content. Mechanical properties of the samples were determined using tensile stress tests. Results found foreskin dermal matrices were devoid of viable cells (p < 0.0001) and the matrix of foreskin dermal matrices was maintained. Basic fibroblast growth factor content doubled within after decellularization (p < 0.0001). Tensile stress tests found no statistically significant differences in the mechanical properties (p < 0.05). These results indicate that the derived foreskin dermal matrix may be suitable in a regenerative approach in the reconstruction of the human foreskin.
Microfluidic device to attain high spatial and temporal control of oxygen

Microfluidic devices have been successfully used to recreate in vitro biological microenvironments, including disease states. However, one constant issue for replicating microenvironments is that atmospheric oxygen concentration (21% O2) does not mimic physiological values (often around 5% O2). We have created a microfluidic device that can control both the spatial and temporal variations in oxygen tensions that are characteristic of in vivo biology. Additionally, since the microcirculation is responsive to hypoxia, we used a 3D sprouting angiogenesis assay to confirm the biological relevance of the microfluidic platform. Our device consists of three parallel connected tissue chambers and an oxygen scavenger channel placed adjacent to these tissue chambers. Experimentally measured oxygen maps were constructed using phosphorescent lifetime imaging microscopy and compared with values from a computational model. The central chamber was loaded with endothelial and fibroblast cells to form a 3D vascular network. Four to six days later, fibroblasts were loaded into the side chambers, and a day later the oxygen scavenger (sodium sulfite) was flowed through the adjacent channel to induce a spatial and temporal oxygen gradient. Our results demonstrate that both constant chronic and intermittent hypoxia can bias vessel growth, with constant chronic hypoxia showing higher degrees of biased angiogenesis. Our simple design provides consistent control of spatial and temporal oxygen gradients in the tissue microenvironment and can be used to investigate important oxygen-dependent biological processes in conditions such as cancer and ischemic heart disease.
Clinical significance of multiparametric MRI and PSA density as predictors of residual tumor (pT0) following radical prostatectomy for T1a-T1b (incidental) prostate cancer

Purpose The aim of this study was to evaluate predictors of residual tumor and clinical prognosis in T1a-T1b (incidental) prostate cancer by analysis of specimens from men undergoing surgery for benign prostatic hyperplasia. Materials and methods We retrospectively reviewed medical records of incidental prostate cancer patients who had undergone radical prostatectomy. Patients whose tumor statuses were further confirmed by prostate biopsy, or who had used androgen deprivation therapy before radical prostatectomy, were excluded. Clinical and pathological parameters were analyzed to evaluate residual tumor and clinical prognosis. We used univariate and multivariate logistic regression analyses, as well as receiver operator characteristics, to predict residual tumor (pT0). Results The final analysis included 95 patients. Among these patients, 67 (70.53%) exhibited residual tumor, whereas 28 (29.47%) did not (pT0). Pathology findings showed that 44 (65.67%), 16 (23.88%), and 7 patients (10.45%) exhibited Gleason scores of G6, G7, and ≥G8, respectively. Fifty-seven and 10 patients exhibited pathologic T stages T2 and T3, respectively. Mean follow-up duration was 70.26 (±34.67) months. Biochemical recurrence was observed in 11 patients; none were pT0 patients. Multivariate logistic regression showed that low prostate-specific antigen density after benign prostatic hyperplasia surgery and invisible lesion on multiparametric magnetic resonance imaging were significantly associated with pT0. Additionally, a combination of these factors showed an increase in the diagnostic accuracy of pT0, compared with mpMRI alone (AUC 0.805, 0.767, respectively); this combination showed sensitivity, specificity, and positive predictive values of 71.6%, 89.3%, and 94.1%, respectively. Conclusion Our results suggest that patients with incidental prostate cancer who have both prostate-specific antigen density ≤0.08 after benign prostatic hyperplasia surgery as well as invisible cancer lesion on multiparametric magnetic resonance imaging should be considered for active surveillance.
Epigenetic Alterations Associated With Early Prenatal Dexamethasone Treatment

Abstract Prenatal treatment with dexamethasone (DEX) reduces virilization in girls with congenital adrenal hyperplasia (CAH). It has potential short- and long-term risks and has been shown to affect cognitive functions. Here, we investigate whether epigenetic modification of DNA during early developmental stages may be a key mediating mechanism by which prenatal DEX treatment could result in poor outcomes in the offspring. We analyzed genome-wide CD4+ T cell DNA methylation, assessed using the Infinium HumanMethylation450 BeadChip array in 29 individuals (mean age = 16.4 ± 5.9 years) at risk for CAH and treated with DEX during the first trimester and 37 population controls (mean age = 17.0 years, SD = 6.1 years). We identified 9672 differentially methylated probes (DMPs) associated with DEX treatment and 7393 DMPs associated with a DEX × sex interaction. DMPs were enriched in intergenic regions located near epigenetic markers for active enhancers. Functional enrichment of DMPs was mostly associated with immune functioning and inflammation but also with nonimmune-related functions. DEX-associated DMPs enriched near single nucleotide polymorphisms (SNPs) associated with inflammatory bowel disease, and DEX × sex-associated DMPs enriched near SNPs associated with asthma. DMPs in genes involved in the regulation and maintenance of methylation and steroidogenesis were identified as well. Methylation in the BDNF, FKBP5, and NR3C1 genes were associated with the performance on several Wechsler Adult Intelligence Scale–Fourth Edition subscales. In conclusion, this study indicates that DNA methylation is altered after prenatal DEX treatment. This finding may have implications for the future health of the exposed individual.
Apigenin Protects the Brain against Ischemia/Reperfusion Injury via Caveolin-1/VEGF In Vitro and In Vivo

Apigenin is a natural flavonoid found in several dietary plant foods as vegetables and fruits. To investigate potential anti-ischemia/reperfusion injury properties of apigenin in vitro, cell proliferation assay, tube formation, cell migration, apoptosis, and autophagy were performed in human brain microvascular endothelial cells (HBMVECs) after oxygen-glucose deprivation/reoxygenation (OGD/R). The effect of apigenin was also explored in rats after middle cerebral artery occlusion/reperfusion (MCAO/R) via neurobehavioral scores, pathological examination, and measurement of markers involved in ischemia/reperfusion injury. Data in vitro indicated that apigenin could prompt cell proliferation, tube formation, and cell migration while inhibiting apoptosis and autophagy by affecting Caveolin-1/VEGF, Bcl-2, Caspase-3, Beclin-1, and mTOR expression. Results in vivo showed that apigenin significantly reduced neurobehavioral scores and volume of cerebral infarction while prompting vascular endothelial cell proliferation by upregulating VEGFR2/CD34 double-labeling endothelial progenitor cell (EPC) number and affecting Caveolin-1, VEGF, and eNOS expression in brain tissue of MCAO/R rats. All the data suggested that apigenin may be protective for the brain against ischemia/reperfusion injury by alleviating apoptosis and autophagy, promoting cell proliferation in HBMVECs of OGD/R, and attenuating brain damage and improved neurological function in rats of MCAO/R through the Caveolin-1/VEGF pathway.
The Human Connectome Project 7 Tesla retinotopy dataset: Description and population receptive field analysis

About a quarter of human cerebral cortex is dedicated mainly to visual processing. The large-scale spatial organization of visual cortex can be measured with functional magnetic resonance imaging (fMRI) while subjects view spatially modulated visual stimuli, also known as “retinotopic mapping. ” One of the datasets collected by the Human Connectome Project involved ultrahigh-field (7 Tesla) fMRI retinotopic mapping in 181 healthy young adults (1.6-mm resolution), yielding the largest freely available collection of retinotopy data. Here, we describe the experimental paradigm and the results of model-based analysis of the fMRI data. These results provide estimates of population receptive field position and size. Our analyses include both results from individual subjects as well as results obtained by averaging fMRI time series across subjects at each cortical and subcortical location and then fitting models. Both the group-average and individual-subject results reveal robust signals across much of the brain, including occipital, temporal, parietal, and frontal cortex as well as subcortical areas. The group-average results agree well with previously published parcellations of visual areas. In addition, split-half analyses show strong within-subject reliability, further demonstrating the high quality of the data. We make publicly available the analysis results for individual subjects and the group average, as well as associated stimuli and analysis code. These resources provide an opportunity for studying fine-scale individual variability in cortical and subcortical organization and the properties of high-resolution fMRI. In addition, they provide a set of observations that can be compared with other Human Connectome Project measures acquired in these same participants.