Miracle-dz/UniFAR-FTUs huggingface dataset:
Delayed GALT reconstitution in duodenum compared to rectum in hiv-infected patients initiating antiretroviral therapy.

BACKGROUND We aimed to characterize the impact of ART initiation on GALT at various sites along the gastrointestinal site. METHODOLOGY Peripheral blood and duodenal and rectal biopsies were obtained from 12 HIV and 33 treatment-naïve HIV subjects at baseline and after 9-months ART. Tissue was digested for immunophenotyping. Inflammatory, bacterial translocation and intestinal damage markers were measured in plasma. RESULTS Twenty-six HIV subjects completed follow-up. The lowest reconstitution of CD4 T-cells and the lowest CD4/CD8 ratio during ART compared to blood were observed in the duodenum with the rectum being either intermediate or approaching blood levels. Regulatory T-cells (Treg) were in higher proportions in the duodenum than the rectum and neither declined significantly during ART. Several correlations with biomarkers of microbial translocation were observed including increases in LTA levels, which reflects gram-positive bacterial translocation, correlated with increases in %CD4 T-cells in duodenum (Rho 0.773, P = 0.033), and with decreases duodenal Treg populations (Rho -0.40, P = 0.045). CONCLUSIONS HIV-mediated immunological disruption is greater in the duodenum than rectum and blood before and during ART. Small intestine damage may represent a unique environment for T-cell depletion, which might be attenuated by interaction with gram positive bacteria.
Higher soluble CD14 levels are associated with lower visuospatial memory performance in Youth with HIV (YWH).

OBJECTIVE HIV-associated neurocognitive disorders persist despite early antiretroviral therapy (ART) and optimal viral suppression. We examined the relationship between immunopathogenesis driven by various pathways of immune activation and discrete neurocognitive performance domains in youth with HIV (YWH). DESIGN Observational cross-sectional study METHODS:: YWH, ages 20 to 28, enrolled in Adolescent Medicine Trials Network 071/101 were assessed for biomarkers of macrophage, lymphocyte activation and vascular inflammation using ELISA/multiplex assays. Standardized neurocognitive tests were performed, and demographically-adjusted z-scores were combined to form indices of attention, motor, executive function, verbal and visuospatial memory. Cross-sectional analysis of the relationship between 18 plasma inflammatory biomarkers and each neurocognitive domain was performed. Linear regression models were fit for each combination of log-transformed biomarker value and neurocognitive domain score, and were adjusted for demographics, socioeconomic status, substance use, depression, CD4 T cell count, HIV viral load, and ART status. RESULTS Study included 128 YWH [mean age 23.8 (SD 1.7) years, 86% men, 68% African American]. Verbal and visuospatial memory domains were most significantly impaired in the cohort (z = -1.59 and -1.0, respectively). Higher sCD14 was associated with impaired visuospatial memory, which remained robust after adjusting for other biomarkers, demographics, and HIV-associated covariates. Among biomarkers of vascular inflammation, sICAM-1 was negatively associated with verbal memory and attention, while sVCAM-1 was positively associated with executive function and visuospatial memory. Specific neurocognitive domains were not associated with sCD163, LPS, or CCL2 levels. CONCLUSIONS Impaired visuospatial memory in YWH is associated with immune activation, as reflected by higher sCD14.
Elevated HbA1c is associated with altered cortical and trabecular microarchitecture in girls with type 1 diabetes.

OBJECTIVE To evaluate differences in skeletal microarchitecture between girls with T1D and controls and to assess factors associated with these differences. DESIGN Cross-sectional comparison. PARTICIPANTS : Girls ages 10-16 years, 62 with T1D and 61 controls. RESULTS Areal bone mineral density (BMD) measured by dual-energy x-ray absorptiometry did not differ between girls with and without T1D. At the distal tibia, trabecular BMD was 7.3 ± 2.9% lower in T1D (p=0.013), with fewer plate-like and axially-aligned trabeculae. Cortical porosity was 21.5 ± 10.5% higher while estimated failure load was 4.7 ± 2.2% lower in T1D (p=0.043 and p=0.037 respectively). At the distal radius, BMD and microarchitecture showed similar differences between the groups but did not reach statistical significance. After stratifying by HbA1c, only those girls with T1D and HbA1c >8.5% differed significantly from controls. P1NP, a marker of bone formation, was lower in T1D while CTX and TRAcP5b, markers of bone resorption and osteoclast number respectively, did not differ. IGF-1 Z-score was lower in T1D, and after adjustment for IGF-1 Z-score, associations between T1D status and trabecular microarchitecture were largely attenuated. CONCLUSIONS Skeletal microarchitecture is altered in T1D early in the course of disease and among those with higher average glycemia. Suppressed bone formation and lower circulating IGF-1 likely contribute to this phenotype.
Ethnic disparities in pain processing among healthy adults: μ-opioid receptor binding potential as a putative mechanism.

Although ethnic differences in pain perception are well documented, the underlying mechanism for these outcomes has not been established. µ-opioid receptor (MOR) function might contribute to this disparity, given that MORs play a key role in pain sensitivity and modulation. However, no study has characterized ethnic differences in MOR physiology. The present study sought to address this knowledge gap by examining differences in µ-selective agonist binding potential (BPND; [C]-Carfentanil) between 27 non-Hispanic Black (NHB) and 27 demographically-similar, non-Hispanic White (NHW) participants. Participants completed questionnaires and two 90-minute high-resolution research tomograph PET imaging sessions. During PET imaging, a capsaicin or control cream was applied to individuals' arms and pain ratings were collected. Bonferroni-corrected PET volumes of interest analyses revealed significantly greater [C]-Carfentanil BPND among NHB participants in bilateral ventral striata [(left): F1,52=16.38, p<. 001; (right): F1,52=21.76, p<. 001], bilateral dorsolateral prefrontal cortices [(left) F1,52=17.3, p<. 001; (right): F1,52=14.17, p<. 001], bilateral subgenual anterior cingulate cortex [(left): F1,52=10.4, p=. 002; (right): F1,52=12.91, p=. 001], and right insula (F1,52=11.0, p=.002). However, there were no significant main effects of Condition or Ethnicity x Condition interaction effects across models, likely attributable to individual variability in the direction of change within groups. BPND values were significantly correlated with pain ratings collected during the capsaicin condition (r range = .34-.46, p range =.01-.001). Results suggest that NHB individuals might have generally greater unoccupied MOR density than NHW peers. Findings have implications for physiological differences underlying ethnicity-related pain disparities. If replicated, these results further emphasize the need for tailored treatments in historically underserved populations.
High fertility: risk factor for carcinoma cervix.

Cancer of the cervix is the most prevalent form of cancer in developing countries and accounts for 25 to 50 per cent of all cancers occurring in Indian women. It is the second most common type of cancer in women throughout the world with approximately 500000 new cases detected each year many of them fatal. Early marriage early coitus early childbearing and repeated child births have been associated with the increasing risk of carcinoma cervix. The somatic consequences of repeated pregnancies may also be exemplified in the clear association between the incidence of cancer of the cervix and high parity. Moreover the natural history of cervical cancer is such that it seems to follow a progressive course from epithelial dysplasia to carcinoma in situ to invasive carcinoma. Fortunately it is possible to detect it early during a preinvasive curable stage by the Pap smear test and to take measures to prevent it from progressing into a life-threatening illness. In view of this family planning enables women to control the interval between births and limit family size so that close and repeated pregnancies are avoided and their health is safeguarded. This study then attempts to assess the correlation between some fertility related factors and the risk of developing carcinoma cervix as also the strength of the association if any. The findings are expected to support the health rationale of family planning thereby contributing to the reproductive health and lives of women besides contributing to fertility decline. (excerpt)
The functional impact of cognition in adults with autism spectrum disorders

Abstract Purpose and aim: The overall aim of this study was to examine the relationship between adaptive function and cognitive factors in young adults diagnosed with autism spectrum disorder (ASD) in adult age. Methods: The study included 30 adults (age 18-30) diagnosed with ASD in adulthood. All participants were clinically referred to an adult psychiatric clinic for assessment. Adaptive functioning was measured with Adaptive Behavior Assessment System – 2nd edition (parent version). Wechsler scales of intelligence and Delis-Kaplan Executive Function System were used to measure intelligence and executive function. Results: We found considerable adaptive functioning deficits regardless of Full Scale Intelligence Quotient (FSIQ) level. FSIQ, working memory and processing speed were positively associated with adaptive functioning. No associations were found between adaptive functioning and cognitive flexibility, inhibition, word generation or shifting. Regression analysis showed that working memory and processing speed predicted 23% of the variance in adaptive functioning in this group. Conclusions: The results suggest that cognitive dysfunction could be an important area for intervention to improve adaptive functioning in ASD.
Effects of shank mass manipulation on sprinting techniques

ABSTRACT The purpose of this study was to determine the effects of shank mass manipulation on the sprinting technique in maximal-speed sprinting. Sixteen well-trained male athletes sprinted with and without an additional 15% of shank mass attached to the shank centre of mass. Kinematic data were collected using a 12-camera motion analysis system and analysed using linear regression analyses with categorical variables and paired t-tests. The sprinting speed ( p < 0.01), knee flexion angle at landing ( p = 0.028), and maximum hip flexion angular velocity ( p = 0.029) decreased; contact time ( p < 0.01) increased; and step length, step frequency, and other analysed technique measures of maximal-speed sprinting were unchanged ( p ≥ 0.12) with shank mass manipulation, compare with no manipulation. The relationships of sprinting speed with critical linear and angular kinematics at landing, take-off and swing in maximal-speed sprinting were not affected by the shank mass manipulation. These results suggest that 15% shank mass manipulation does not change the sprinting technique of well-trained male athletes in maximal-speed sprinting. This supports the use of shank mass manipulation as a training method for well-trained sprinters; however, a change in correlations between sprinting speed and technique measures should be considered during such training.
Extracellular Vesicles: How a Circulating Biomarker Can Double As a Regulator of Blood Pressure.

An extracellular vesicle (EV) is a general term for a group of heterogeneous membrane-bound structures that are secreted from a wide range of cell types, including those comprising the cardiovascular and immune systems. From cardiovascular disease to cancer, EVs are quickly being recognized as potentially useful biomarkers for screening disease progression in part due to their presence in easily accessible bodily fluids such as urine, blood, and saliva. Additionally, EVs are emerging as vehicles of intercellular communication between parent cells (source of EVs) and recipient cells (target of EV action) throughout the body. Thus, it is not surprising that since the first observation of EVs released from maturing reticulocytes during erythrocyte development, the burgeoning field has focused on how and why cells synthesize and release these sub-micron structures, in particular, during pathophysiological states. Considering that EVs are circulating factors, the effect on vascular structures, the primary conduit, and distributor of blood has been relatively understudied. In this issue of Hypertension, Good et al demonstrate a novel role for EVs in regulating arterial reactivity and ultimately blood pressure. Extracellular vesicles can be divided into multiple subcategories—the most relevant to the work of Good et al being exosomes and microvesicles (see van Niel et al for additional classifications). Exosomes, typically 50 to 150 nm in diameter, are intraluminal vesicles released from multivesicular endosomes as they fuse with the plasma membrane of the parent cell (Figure, left). This vesicular release occurs both via endosomal sorting complexes required for transport-dependent and endosomal sorting complexes required for transport-independent mechanisms. Much like neurotransmitter release from synaptic boutons, exosome secretion can be a calcium-dependent process which utilizes SNARE proteins to initiate the fusion of the multivesicular endosome membrane with the plasma membrane to cause release of the exosomes and other vesicular cargo in a paracrine fashion. Microvesicles, which range from 50 nm up to 1 μm in diameter, can also act as paracrine mediators; however, the primary pathway of release is through outward budding and fission of the plasma membrane (Figure, left). Despite the recognition of these distinct pathways for EV release, a number of technical limitations hinder the ability to clearly differentiate EV sources experimentally. Indeed, there is currently no gold-standard method of EV isolation. Despite these limitations, cell-type specific markers have been used to identify the potential parent cell of origin. Although Good et al demonstrated that the size, morphology, and concentration of the EVs were unchanged in hypertension, they did observe differential expression of cell surface markers (CD31+ and CD45+) in hypertensive rats compared with both prehypertensive rats and age-matched normotensive controls. These data support the idea that EV composition changes following the development of hypertension.
Impact of PD‐L1 expression and human papillomavirus status in anti‐PD1/PDL1 immunotherapy for head and neck squamous cell carcinoma—Systematic review and meta‐analysis

Programmed cell death‐1 (PD‐1) pathway inhibition in head and neck squamous cell carcinoma (HNSCC) has demonstrated inconsistent efficacy regarding human papillomavirus (HPV) status and PD‐L1 expression. This study compared outcomes in HNSCC in the context of PD‐L1 and HPV expression. Outcomes: PD‐L1 and HPV expression; overall survival (OS), and tumor response (ORR). 1088 patients received PD‐1/L1 inhibitors. Four methodologies were identified in determining PD‐L1 expression, most commonly using the Dako PD‐L1 IHC 22C3 pharmaDx assay. Using a 1% threshold, ORR was greater for PD‐L1 expressers vs non‐expressers (18.9%, CI 16.1‐21.8 v 8.8% CI 5.3‐13.7, P = 0.009), as was OS at 6 months (60.6%, CI 49.2‐71.4 v 49.0%, CI 39.1‐59.0, P = 0.04) but not at 12 or 18 months. No advantages were identified for HPV expressers. Patients expressing PD‐L1 may have a better tumor response and OS. No impact on survival or response was observed based on HPV status.
Free-living Evaluation of Laboratory-based Activity Classifiers in Preschoolers

ABSTRACT Machine learning classification models for accelerometer data are potentially more accurate methods to measure physical activity in young children than traditional cut point methods. However, existing algorithms have been trained on laboratory-based activity trials, and their performance has not been investigated under free-living conditions. Purpose This study aimed to evaluate the accuracy of laboratory-trained hip and wrist random forest and support vector machine classifiers for the automatic recognition of five activity classes: sedentary (SED), light-intensity activities and games (LIGHT_AG), walking (WALK), running (RUN), and moderate to vigorous activities and games (MV_AG) in preschool-age children under free-living conditions. Methods Thirty-one children (4.0 ± 0.9 yr) were video recorded during a 20-min free-living play session while wearing an ActiGraph GT3X+ on their right hip and nondominant wrist. Direct observation was used to continuously code ground truth activity class and specific activity types occurring within each class using a bespoke two-stage coding scheme. Performance was assessed by calculating overall classification accuracy and extended confusion matrices summarizing class-level accuracy and the frequency of specific activities observed within each class. Results Accuracy values for the hip and wrist random forest algorithms were 69.4% and 59.1%, respectively. Accuracy values for hip and wrist support vector machine algorithms were 66.4% and 59.3%, respectively. Compared with the laboratory cross validation, accuracy decreased by 11%–15% for the hip classifiers and 19%–21% for the wrist classifiers. Classification accuracy values were 72%–78% for SED, 58%–79% for LIGHT_AG, 71%–84% for MV_AG, 9%–15% for WALK, and 66%–75% for RUN. Conclusion The accuracy of laboratory-based activity classifiers for preschool-age children was attenuated when tested on new data collected under free-living conditions. Future studies should train and test machine learning activity recognition algorithms using accelerometer data collected under free-living conditions.
Risk of malignancy in “atypia of undetermined significance” category of salivary gland fine‐needle aspiration: A bi‐institutional experience

Many prior institutional and multi‐institutional studies have applied the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) retrospectively to their specimens to determine the risk of malignancy (ROM) of each category. Most of these studies focused on general assessment of the system and risk classification. However, there seems to be less focus on the category of atypia of undetermined significance (AUS) that could be attributed to the low number of cases that could fit into this category. Herein, we present a bi‐institutional experience with this category.
Wood allocation trade‐offs between fiber wall, fiber lumen, and axial parenchyma drive drought resistance in neotropical trees

Abstract Functional relationships between wood density and measures of xylem hydraulic safety and efficiency are ambiguous, especially in wet tropical forests. In this meta‐analysis, we move beyond wood density per se and identify relationships between xylem allocated to fibers, parenchyma, and vessels and measures of hydraulic safety and efficiency. We analyzed published data of xylem traits, hydraulic properties and measures of drought resistance from neotropical tree species retrieved from 346 sources. We found that xylem volume allocation to fiber walls increases embolism resistance, but at the expense of specific conductivity and sapwood capacitance. Xylem volume investment in fiber lumen increases capacitance, while investment in axial parenchyma is associated with higher specific conductivity. Dominant tree taxa from wet forests prioritize xylem allocation to axial parenchyma at the expense of fiber walls, resulting in a low embolism resistance for a given wood density and a high vulnerability to drought‐induced mortality. We conclude that strong trade‐offs between xylem allocation to fiber walls, fiber lumen, and axial parenchyma drive drought resistance in neotropical trees. Moreover, the benefits of xylem allocation to axial parenchyma in wet tropical trees might not outweigh the consequential low embolism resistance under more frequent and severe droughts in a changing climate.
MicroRNA‐based regulatory circuit involved in sperm infertility

miRNAs (MicroRNAs), known as noncoding and important endogenous factors regulating the expression protein‐coding genes, are vital regulators in each biological process. Thus, this study aims to explore the key role of four microRNAs in regulating the spermatogenesis. To conduct this experiment, 55 infertile and fertile men provided the study with the sperm and testicular tissue samples. To study the spermatozoa in terms of the morphology, Diff‐Quick was applied. Then, quantitative real‐time polymerase chain reaction (RT‐PCR) was conducted on samples. Our data indicated that in contrast to the miR‐15b, significant increasing of miR‐383 and miR‐122 occurred in both severe oligoasthenoteratozoospermia (SOAT) and moderate oligoasthenoteratozoospermia (MOAT) compared to normal sperm group (N). In addition, it was observed that miR‐15b and miR‐122 increased in patients with nonobstructive azoospermia (NOA) compared with obstructive azoospermia (OA) group. Expression levels of target genes including P53, CASPASE‐9 and CYCLIN D1 underwent principle changes according to miRNAs expression level. Our finding indicated that miRNAs had essential role in the regulation of spermatogenesis, and their expression altering was associated with sperm abnormalities. Thus, microRNAs can be introduced as useful biomarkers to determine male infertility reasons to choose the effective treatment.
The progressive alteration of urine metabolomic profiles of rats following long-term and low-dose exposure to permethrin

Abstract Background: Permethrin is a type of widely used pyrethroid pesticide. Although acute toxicity of permethrin has been well-characterised, the non-acute toxicity of permethrin upon long-term exposure at low dose has been seldom studied yet. The current study investigates the time-course change of the metabolomic profiles of urine following the low level long-term exposure of permethrin and identified biomarkers of the chronic toxicity of permethrin. Methods: Male Wistar rats were administrated orally with permethrin (75 mg/kg body weight/day, 1/20 LD50) daily for consecutive 90 days. The urine samples from day 30, day 60, and day 90 after the first dosing were collected and analysed by 1H NMR spectrometry. Serum biochemical analysis was also carried out. Results: Permethrin caused significant changes in the urine metabolites such as taurine, creatinine, acetate, lactate, dimethylamine, dimethylglycine, and trimethylamine-N-oxide. These biological markers indicated prominent kidney and liver toxicity induced by permethrin. However, there was no change in serum biochemical parameters for the toxicity, indicating that metabolomic approach was much more sensitive in detecting the chronic toxicity. Conclusion: The time-course alteration of metabolomic profiles of the urine based on 1H NMR reflects the progressive development of the chronic toxicity with the long-term low-level exposure of permethrin.