Miracle-dz/UniFAR-FTUs huggingface dataset:
Impairment of cerebrovascular reactivity in response to hypercapnic challenge in a mouse model of repetitive mild traumatic brain injury

Incidences of repetitive mild TBI (r-mTBI), like those sustained by contact sports athletes and military personnel, are thought to be a risk factor for development of neurodegenerative disorders. Those suffering from chronic TBI-related illness demonstrate deficits in cerebrovascular reactivity (CVR), the ability of the cerebral vasculature to respond to a vasoactive stimulus. CVR is thus an important measure of traumatic cerebral vascular injury (TCVI), and a possible in vivo endophenotype of TBI-related neuropathogenesis. We combined laser speckle imaging of CVR in response to hypercapnic challenge with neurobehavioral assessment of learning and memory, to investigate if decreased cerebrovascular responsiveness underlies impaired cognitive function in our mouse model of chronic r-mTBI. We demonstrate a profile of blunted hypercapnia-evoked CVR in the cortices of r-mTBI mice like that of human TBI, alongside sustained memory and learning impairment, without biochemical or immunohistopathological signs of cerebral vessel laminar or endothelium constituent loss. Transient decreased expression of alpha smooth muscle actin and platelet-derived growth factor receptor β, indicative of TCVI, is obvious only at the time of the most pronounced CVR deficit. These findings implicate CVR as a valid preclinical measure of TCVI, perhaps useful for developing therapies targeting TCVI after recurrent mild head trauma.
Myeloid-derived suppressor cell cytokine secretion as prognostic factor in myelodysplastic syndromes

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that play a critical immunosuppressive role in the tumour micro-environment. Although biological research on MDSCs has made progress, the relationship between the secretion of cytokines by MDSCs and poor prognosis is not clear, and there are no criteria to measure the functional status of MDSCs. Here, we detected the mRNA expression of IL-10, IL-12, TGF-β and TNF-α in MDSCs and the levels of these cytokines in MDSC culture supernatants of patients with myelodysplastic syndromes, and quantified the functional status of MDSCs by IL-10/IL-12 ratio and TGF-β/TNF-α ratio. We found that the ratio of IL-10/IL-12 and TGF-β/TNF-α was significantly higher in higher-risk MDS than in lower-risk MDS and normal control groups. The TGF-β/TNF-α ratio in MDSCs was positively correlated with the percentage of blast cells and was negatively correlated with the percentage of CD3+CD8+ T lymphocytes. Meanwhile, the TGF-β/TNF-α ratio was higher in patients with a lower absolute neutrophil count. It suggested that MDSCs in higher-risk MDS have a stronger immunosuppressive effect and might be related to poor prognosis. Quantifying the functional status of MDSCs with IL-10/IL-12 and TGF-β/TNF-α ratio might help to evaluate the balance of cellular immunity of MDSCs in MDS.
Hybrid Fluorescent Poly(silsesquioxanes) with Amide- and Triazole-Containing Side Groups for Light Harvesting and Cation Sensing

Hybrid polymers containing pyrene (Py) units bound to linear poly(silsesquioxane) (LPSQ) chains through flexible linkers containing heteroatoms (S, N, O) (LPSQ-triazole-Py and LPSQ-amide-Py) exhibit intense fluorescence emission, both in very diluted solutions (c = 10−8 mol/L) and in the solid state. The materials are thermally stable and exhibit good thin film forming abilities. Their optical and physicochemical properties were found to be strongly dependent on the structure of the side chains. Comparative studies with octahedral silsesquioxane (POSS) analogues (POSS-triazole-Py and POSS-amide-Py) emphasized the role of the specific double-strand architecture of the LPSQ backbone and distribution of side Py groups for their photo-luminescent properties. The new hybrid materials were tested as fluorescence energy donors to red-emitting dyes (Nile Red and Coumarine 6). All the silsesquioxanes studied were found to be able to transfer FL emission energy to Coumarin 6, irrespectively of their spatial structure. However, due to the differences in the wavelength range of FL emission, only LPSQ-triazole-Py were able to act as energy donors to Nile Red. The Py-grafted LPSQ may be also applied for development of soluble and highly emissive chemosensors. Their fluorescent nature was explored for the detection of Cu(II), Fe(III), Co(II), Ag(I), Hg(II), Mg(II), Ca(II), Pb(II) and Zn(II). The morphology of the side chains and hydrogen-bonding interactions influenced the sensing capacity of all the studied materials.
Prevalence of symptoms and associated factors across menopause status in Taiwanese women

Supplemental Digital Content is available in the text Abstract Objective: To investigate the prevalence of symptoms and associated factors in Taiwanese women calling a menopause hotline. Methods: A cross-sectional, descriptive, epidemiological study was performed on 20,882 women aged 40 to 89 years registered in the menopause consultation database of the nationwide toll-free consultation hotline for menopause-related issues from January 2006 to December 2016. The data included demography, sources of menopausal health care, and menopause/midlife symptoms scale. Results: The mean menopausal age was 49.6 ± 4 years. The prevalence of the symptoms increased with the progress of the menopausal stages, and the differences between stages were significant. The top five symptoms reported on a menopause hot line were memory loss (66.9%), fatigue (66.5%), insomnia (59.6%), depressed mood (58.5%), and back pain (58.2%). Of the women, 23.5% did visit a medical facility for menopausal problems mainly the department of gynecology. More than half of the women (56.4%) opted for medical personnel as the preferred channel for obtaining information concerning menopause. Women who had a higher education level, were single, had no children, were not experiencing the empty-nest phenomenon, were employed, had no chronic disease, were premenopausal, had never received hormone therapy, and had not visited medical facilities scored the lowest in menopause/midlife symptoms. Conclusions: Compared with premenopausal and perimenopausal women, postmenopausal women experience the most severe symptoms. Therefore, establishing a menopause consultation hotline answered by medical personnel and implementing support for postmenopausal women to obtain strategies to alleviate symptoms are required and necessary. Video Summary: http://links.lww. com/MENO/A651.
Universal third-trimester ultrasonic screening using fetal macrosomia in the prediction of adverse perinatal outcome: A systematic review and meta-analysis of diagnostic test accuracy

Background The effectiveness of screening for macrosomia is not well established. One of the critical elements of an effective screening program is the diagnostic accuracy of a test at predicting the condition. The objective of this study is to investigate the diagnostic effectiveness of universal ultrasonic fetal biometry in predicting the delivery of a macrosomic infant, shoulder dystocia, and associated neonatal morbidity in low- and mixed-risk populations. Methods and findings We conducted a predefined literature search in Medline, Excerpta Medica database (EMBASE), the Cochrane library and ClinicalTrials.gov from inception to May 2020. No language restrictions were applied. We included studies where the ultrasound was performed as part of universal screening and those that included low- and mixed-risk pregnancies and excluded studies confined to high risk pregnancies. We used the estimated fetal weight (EFW) (multiple formulas and thresholds) and the abdominal circumference (AC) to define suspected large for gestational age (LGA). Adverse perinatal outcomes included macrosomia (multiple thresholds), shoulder dystocia, and other markers of neonatal morbidity. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Meta-analysis was carried out using the hierarchical summary receiver operating characteristic (ROC) and the bivariate logit-normal (Reitsma) models. We identified 41 studies that met our inclusion criteria involving 112,034 patients in total. These included 11 prospective cohort studies (N = 9986), one randomized controlled trial (RCT) (N = 367), and 29 retrospective cohort studies (N = 101,681). The quality of the studies was variable, and only three studies blinded the ultrasound findings to the clinicians. Both EFW >4,000 g (or 90th centile for the gestational age) and AC >36 cm (or 90th centile) had >50% sensitivity for predicting macrosomia (birthweight above 4,000 g or 90th centile) at birth with positive likelihood ratios (LRs) of 8.74 (95% confidence interval [CI] 6.84–11.17) and 7.56 (95% CI 5.85–9.77), respectively. There was significant heterogeneity at predicting macrosomia, which could reflect the different study designs, the characteristics of the included populations, and differences in the formulas used. An EFW >4,000 g (or 90th centile) had 22% sensitivity at predicting shoulder dystocia with a positive likelihood ratio of 2.12 (95% CI 1.34–3.35). There was insufficient data to analyze other markers of neonatal morbidity. Conclusions In this study, we found that suspected LGA is strongly predictive of the risk of delivering a large infant in low- and mixed-risk populations. However, it is only weakly (albeit statistically significantly) predictive of the risk of shoulder dystocia. There was insufficient data to analyze other markers of neonatal morbidity.
BRD4 inhibition sensitizes renal cell carcinoma cells to the PI3K/mTOR dual inhibitor VS-5584

Activation of the PI3K/AKT/mTOR pathway promotes the progression of renal cell carcinoma (RCC). This study tested the anti-RCC cell activity of the PI3K/mTOR dual inhibitor, VS-5584. We show that VS-5584 inhibited PI3K/AKT/mTORC1/2 activation in established (786-O and A498 lines) and primary RCC cells, thereby suppressing cell survival, proliferation, migration and cell cycle progression. VS-5584 induced significant apoptosis in RCC cells. A daily single oral dose of VS-5584 (20 mg/kg) significantly inhibited 786-O tumor growth in vivo. VS-5584 treatment of 786-O tumor xenografts and RCC cells resulted in feedback upregulation of bromodomain-containing protein 4 (BRD4). Furthermore, BRD4 inhibition (by JQ1 and CPI203), knockdown or complete knockout potentiated VS-5584-induced RCC cell death and apoptosis. Conversely, forced overexpression of BRD4 attenuated the cytotoxicity of VS-5584 in 786-O cells. Collectively, VS-5584 potently inhibits RCC cell proliferation and survival. Its anti-tumor activity is further enhanced by the targeted inhibition of BRD4.
Diversity Analysis and Genetic Relationships among Local Brazilian Goat Breeds Using SSR Markers

Simple Summary This study aimed to evaluate the genetic diversity of six groups of native Brazilian goats using a panel of single sequence repeats (SSRs). Results indicated a definite genetic differentiation among the Brazilian goat herd, which indicates the existence of at least four breeds according to the international concepts (Moxotó and Repartida; the Grauna and Serrana Azul; Canindé and Marota breeds). Abstract The genetic diversity of six Brazilian native goats was reported using molecular markers. Hair samples of 332 animals were collected from different goat breeds (Moxotó, Canindé, Serrana Azul, Marota, Repartida, and Graúna) from five states of Northeast Brazil (Paraíba, Pernambuco, Rio Grande do Norte, Bahia, and Piauí). A panel of 27 microsatellites or single sequence repeats (SSRs) were selected and amplified using a polymerase chain reaction (PCR) technique. All populations showed an average allele number of over six. The mean observed heterozygosity for Brazilian breeds was superior to 0.50. These results demonstrated the high genetic diversity in the studied populations with values ranging from 0.53 (Serrana Azul) to 0.62 (Repartida). The expected average heterozygosity followed the same trend ranging from 0.58 (Serrana Azul) to 0.65 (Repartida), and the values obtained are very similar for all six breeds. The fixation index (Fis) had values under 10% except for the Moxotó breed (13%). The mean expected heterozygosity of all Brazilian populations was over 0.50. Results indicated a within-breed genetic variability in the Brazilian breeds based on the average number of alleles and the average observed heterozygosity. The interbreed genetic diversity values showed proper genetic differentiation among local Brazilian goat breeds.
Wing: A suitable nonlethal tissue type for repeatable and rapid telomere length estimates in bats

Telomeres are used increasingly in ecology and evolution as biomarkers for ageing and environmental stress, and are typically measured from DNA extracted from nonlethally sampled blood. However, obtaining blood is not always possible in field conditions and only limited amounts can be taken from small mammals, such as bats, which moreover lack nucleated red blood cells and hence yield relatively low amounts of DNA. As telomere length can vary within species according to age and tissue, it is important to determine which tissues serve best as a representation of the organism as a whole. Here, we investigated whether wing tissue biopsies, a rapid and relatively noninvasive tissue collection method, could serve as a proxy for other tissues when measuring relative telomere length (rTL) in the Egyptian fruit bat (Rousettus aegyptiacus). Telomeres were measured from blood, brain, heart, kidney, liver lung, muscle and wing, and multiple wing biopsies were taken from the same individuals to determine intra‐individual repeatability of rTL measured by using qPCR. Wing rTL correlated with rTL estimates from most tissues apart from blood. Blood rTL was not significantly correlated with rTL from any other tissue. Blood and muscle rTLs were significantly longer compared with other tissues, while lung displayed the shortest rTLs. Individual repeatability of rTL measures from wing tissue was high (>70%). Here we show the relationships between tissue telomere dynamics for the first time in a bat, and our results provide support for the use of wing tissue for rTL measurements.
Endogenous Anti-Cancer Candidates in GPCR, ER Stress, and EMT

The majority of cellular responses to external stimuli are mediated by receptors such as G protein-coupled receptors (GPCRs) and systems including endoplasmic reticulum stress (ER stress). Since GPCR signalling is pivotal in numerous malignancies, they are widely targeted by a number of clinical drugs. Cancer cells often negatively modulate GPCRs in order to survive, proliferate and to disseminate. Similarly, numerous branches of the unfolded protein response (UPR) act as pro-survival mediators and are involved in promoting cancer progression via mechanisms such as epithelial to mesenchymal transition (EMT). However, there are a few proteins among these groups which impede deleterious effects by orchestrating the pro-apoptotic phenomenon and paving a therapeutic pathway. The present review exposes and discusses such critical mechanisms and some of the key processes involved in carcinogenesis.
Immediate Antiretroviral Therapy: The Need for a Health Equity Approach

Immediate antiretroviral therapy (iART), defined as same-day initiation of ART or as soon as possible after diagnosis, has recently been recommended by global and national clinical care guidelines for patients newly diagnosed with human immunodeficiency virus (HIV). Based on San Francisco’s Rapid ART Program Initiative for HIV Diagnoses (RAPID) model, most iART programs in the US condense ART initiation, insurance acquisition, housing assessment, and mental health and substance use evaluation into an initial visit. However, the RAPID model does not explicitly address structural racism and homophobia, HIV-related stigma, medical mistrust, and other important factors at the time of diagnosis experienced more poignantly by African American, Latinx, men who have sex with men (MSM), and transgender patient populations. These factors negatively impact initial and subsequent HIV care engagement and exacerbate significant health disparities along the HIV care continuum. While iART has improved time to viral suppression and linkage to care rates, its association with retention in care and viral suppression, particularly in vulnerable populations, remains controversial. Considering that in the US the HIV epidemic is sharply defined by healthcare disparities, we argue that incorporating an explicit health equity approach into the RAPID model is vital to ensure those who disproportionately bear the burden of HIV are not left behind.
COVID‐19 Increases Online Searches for Emotional and Health‐Related Terms

Background The COVID‐19 pandemic has powerfully shaped people’s lives. The current work investigated the emotional and behavioral reactions people experience in response to COVID‐19 through their internet searches. We hypothesised that when the prevalence rates of COVID‐19 increase, people would experience more fear, which in turn would predict more searches for protective behaviors, health‐related knowledge, and panic buying. Methods Prevalence rates of COVID‐19 in the United States, the United Kingdom, Canada, and Australia were used as predictors. Fear‐related emotions, protective behaviors, seeking health‐related knowledge, and panic buying were measured using internet search volumes in Google Trends. Results We found that increased prevalence rates of COVID‐19 were associated with more searches for protective behaviors, health knowledge, and panic buying. This pattern was consistent across four countries, the United States, the United Kingdom, Canada, and Australia. Fear‐related emotions explained the associations between COVID‐19 and the content of their internet searches. Conclusions Findings suggest that exposure to COVID‐19 prevalence and fear‐related emotions may motivate people to search for relevant health‐related information so as to protect themselves from the pandemic.
Propagation temperature, PPFD, auxin treatment, cutting size and cutting position affect root formation, axillary bud growth and shoot development in miniature rose (Rosa hybrida L.) plants and alter homogeneity

Summary Rooting and growth responses of miniature rose cuttings were investigated in an experiment in which four propagation temperatures, two photosynthetic photon flux densities (PPFDs) with five auxin (IBA) concentrations, cutting sizes and cutting positions, were combined factorially in a response-surface design. Most prominently, temperature, cutting size and auxin and their interactions, influenced root and shoot growth. A propagation temperature of 24.6°C, and IBA concentrations between 10–3 and 10–1M, depending on temperature, were optimal for root formation. Root formation in extra short cuttings was delayed at low IBA concentrations. Regarding root formation, IBA could substitute for increased temperature as well as for increased cutting size. Onset of axillary bud growth was fastest at 24.6°C, and delayed in extra short cuttings. Application of IBA at 10–4 to 10–3M was optimal for axillary bud growth. By increasing the IBA concentration both time to flowering and plant height increased at 24.6°C. In cuttings from higher positions on stock plants, axillary shoots enhanced their growth to flowering, became shorter, and weighed less, suggesting occurrence of positional effects (topophysis). The growth rate increased with increasing IBA concentration, as well as from medial to low positioned cuttings. Increasing propagation PPFD from 46 to 72 µmol m–2s–1 did not affect the parameters. Time to axillary bud growth and time to first flower were related to time-to-visible root. Fast formation of roots apparently resulted in fast axillary bud growth. In time-to-visible root and axillary bud growth, the smallest variation between plants was found at optimal ranges for temperature, IBA concentration and cutting size, and further factors optimal for root formation and axillary bud growth provided the most synchronized plant development.
Deletion of the Gene Encoding the NMDA Receptor GluN1 Subunit in Schwann Cells Causes Ultrastructural Changes in Remak Bundles and Hypersensitivity in Pain Processing

Abnormalities in interactions between sensory neurons and Schwann cells (SCs) may result in heightened pain processing and chronic pain states. We previously reported that SCs express the NMDA receptor (NMDA-R), which activates cell signaling in response to glutamate and specific protein ligands, such as tissue-type plasminogen activator. Herein, we genetically targeted grin1 encoding the essential GluN1 NMDA-R subunit, conditionally in SCs, to create a novel mouse model in which SCs are NMDA-R-deficient (GluN1– mice). These mice demonstrated increased sensitivity to light touch, pinprick, and thermal hyperalgesia in the absence of injury, without associated changes in motor function. Ultrastructural analysis of adult sciatic nerve in GluN1– mice revealed increases in the density of Aδ fibers and Remak bundles and a decrease in the density of Aβ fibers, without altered g-ratios. Abnormalities in adult Remak bundle ultrastructure were also present including aberrant C-fiber ensheathment, distances between axons, and increased poly-axonal pockets. Developmental and post radial sorting defects contributed to altered nerve fiber densities in adult. Uninjured sciatic nerves in GluN1– mice did not demonstrate an increase in neuroinflammatory infiltrates. Transcriptome profiling of dorsal root ganglia (DRGs) revealed 138 differentially regulated genes in GluN1– mice. One third of the regulated genes are known to be involved in pain processing, including sprr1a, npy, fgf3, atf3, and cckbr, which were significantly increased. The intraepidermal nerve fiber density (IENFD) was significantly decreased in the skin of GluN1– mice. Collectively, these findings demonstrate that SC NMDA-R is essential for normal PNS development and for preventing development of pain states. SIGNIFICANCE STATEMENT Chronic unremitting pain is a prevalent medical condition; however, the molecular mechanisms that underlie heightened pain processing remain incompletely understood. Emerging data suggest that abnormalities in Schwann cells (SCs) may cause neuropathic pain. We established a novel mouse model for small fiber neuropathy (SFN) in which grin1, the gene that encodes the NMDA receptor (NMDA-R) GluN1 subunit, is deleted in SCs. These mice demonstrate hypersensitivity in pain processing in the absence of nerve injury. Changes in the density of intraepidermal small fibers, the ultrastructure of Remak bundles, and the transcriptome of dorsal root ganglia (DRGs) provide possible explanations for the increase in pain processing. Our results support the hypothesis that abnormalities in communication between sensory nerve fibers and SCs may result in pain states.