Miracle-dz/UniFAR-FTUs huggingface dataset:
Exosomes containing HIV protein Nef reorganize lipid rafts potentiating inflammatory response in bystander cells

HIV infection has a profound effect on “bystander” cells causing metabolic co-morbidities. This may be mediated by exosomes secreted by HIV-infected cells and containing viral factors. Here we show that exosomes containing HIV-1 protein Nef (exNef) are rapidly taken up by macrophages releasing Nef into the cell interior. This caused down-regulation of ABCA1, reduction of cholesterol efflux and sharp elevation of the abundance of lipid rafts through reduced activation of small GTPase Cdc42 and decreased actin polymerization. Changes in rafts led to re-localization of TLR4 and TREM-1 to rafts, phosphorylation of ERK1/2, activation of NLRP3 inflammasome, and increased secretion of pro-inflammatory cytokines. The effects of exNef on lipid rafts and on inflammation were reversed by overexpression of a constitutively active mutant of Cdc42. Similar effects were observed in macrophages treated with exosomes produced by HIV-infected cells or isolated from plasma of HIV-infected subjects, but not with exosomes from cells and subjects infected with ΔNef-HIV or uninfected subjects. Mice injected with exNef exhibited monocytosis, reduced ABCA1 in macrophages, increased raft abundance in monocytes and augmented inflammation. Thus, Nef-containing exosomes potentiated pro-inflammatory response by inducing changes in cholesterol metabolism and reorganizing lipid rafts. These mechanisms may contribute to HIV-associated metabolic co-morbidities.
Dodecamers derived from the crystal structure were found in the pre-crystallization solution of the transaminase from the thermophilic bacterium Thermobaculum terrenum by small-angle X-ray scattering

Abstract The pre-crystallization solution of the transaminase from Thermobaculum terrenum (TaTT) has been studied by small-angle X-ray scattering (SAXS). Regular changes in the oligomeric composition of the protein were observed after the addition of the precipitant. Comparison of the observed oligomers with the crystal structure of TaTT (PDB ID 6GKR) shows that dodecamers may act as building blocks in the growth of transaminase single crystals. Correlating of these results to the similar X-ray studies of other proteins suggests that SAXS may be a valuable tool for searching optimum crystallization conditions. Abbreviation SAXS small-angle X-ray scattering Ta transaminase TaTT transaminase from Thermobaculum terrenum PLP pyridoxal-5’-phosphate R-PEA R-(þ)-1-phenylethylamine BCAT branched-chain amino acid aminotransferase DAAT D-aminoacid aminotransferase R-TA R-amine:pyruvate transaminase Communicated by Ramaswamy H. Sarma
Notes from the Field: Targeted Biomonitoring for GenX and Other Per- and Polyfluoroalkyl Substances Following Detection of Drinking Water Contamination — North Carolina, 2018

Targeted Biomonitoring for GenX and Other Perand Polyfluoroalkyl Substances Following Detection of Drinking Water Contamination — North Carolina, 2018 Jamie R. Pritchett, MTox1; Jessica L. Rinsky, PhD1; Beth Dittman, MS1; Ariel Christensen, MPH1; Rick Langley, MD1; Zack Moore, MD1; Aaron T. Fleischauer, PhD1,2; Kate Koehler1; Antonia M. Calafat, PhD3; Rachel Rogers, PhD4; Laconial Esters5; Rodney Jenkins5; Faye Collins6; Debra Conner6; Patrick Breysse, PhD3,4
Alteration of testicular regulatory and functional molecules following long‐time exposure to 900 MHz RFW emitted from BTS

The aim of this investigation was to evaluate changes in testosterone and some of the functional and regulatory molecules of testis such as P450scc, steroidogenic acute regulatory protein (StAR), tumour necrosis factor‐α (TNF‐α), interleukin‐1α (IL‐1α), interleukin‐1β (IL‐1β) and nerve growth factor (NGF) following exposure to 900 MHz radio frequency (RF). Thirty adult male Sprague Dawley rats (190 ± 20 g BW) were randomly classified in three equal groups, control (sham, without any exposure), short‐time exposure (2 hr) (STE) and long‐time exposure (4 hr) (LTE). The exposure was performed for 30 consecutive days. The testosterone level in both exposed groups was significantly less than control (p < .05). Level of TNF‐α in both exposed groups was significantly greater than control (p < .05). IL‐1α and NGF levels in LTE were significantly higher than the STE and control groups (p < .05). Level of IL‐1β in LTE was significantly higher than control (p < .05). Expression of both P450scc and StAR mRNA was significantly down‐regulated in both exposed groups compared to control (p < .05). Our results showed that RFW can affect testis and reproductive function through changes in factors, which are important during steroidogenesis, and also through changes in inflammatory factors, which regulate Leydig cell functions.
Projected Population Benefit of Increased Effectiveness and Coverage of Influenza Vaccination on Influenza Burden - United States.

BACKGROUND Vaccination is the best way to prevent influenza; however, greater benefit could be achieved. To help guide research and policy agendas, we aimed to quantify the magnitude of influenza disease that would be prevented through targeted increases in vaccine effectiveness (VE) or coverage. METHODS For three influenza seasons (2011-12, 2015-16, and 2017-18) we used a mathematical model to estimate the number of prevented influenza-associated illnesses, medically-attended illnesses, and hospitalizations across five age groups. Compared with estimates of prevented illness during each season, given observed VE and coverage, we explored the number of additional outcomes that would be prevented from a 5% absolute increase in VE or coverage or achieving 60% VE or 70% coverage. RESULTS During the 2017-18 season, compared with the burden already prevented by influenza vaccination, a 5% absolute VE increase would prevent an additional 1,050,000 illnesses and 25,000 hospitalizations (76% among those aged ≥65 years) while achieving 60% VE would prevent an additional 190,000 hospitalizations. A 5% coverage increase would result in 785,000 fewer illnesses (56% among those aged 18-64 years) and 11,000 fewer hospitalizations; reaching 70% would prevent an additional 39,000 hospitalizations. CONCLUSIONS Small, attainable improvements in effectiveness or coverage of influenza vaccine could lead to substantial additional reductions in influenza burden in the U.S. Improvements in VE would have the greatest impact in reducing hospitalizations in adults aged ≥65 years and coverage improvements would have the largest benefit in reducing illnesses in adults aged 18-49 years.
Genomic Identification and Expression Analysis of the Cathelicidin Gene Family of the Forest Musk Deer

Simple Summary Cathelicidins are a group of host defense peptides in vertebrates with both antimicrobial and immunomodulatory activities. In the present study, we identified the entire repertoire of the cathelicidin gene family from the forest musk deer genome. Sequence comparison, phylogenetic topology, and gene and genomic organizations collectively suggest that all cathelicidin genes have already been fixed in the genome of forest musk deer before the split of moschidae and bovidae, while independent pseudogenization events have occurred after species divergence. In addition, real-time PCR analysis suggested that all functional cathelicidins play important roles in the immune system. The results of this study will be helpful for further evolutionary and functional studies. Abstract The forest musk deer (Moschus berezovskii) is a small-sized artiodactyl species famous for the musk secreted by adult males. In the captive population, this species is under the threat of infection diseases, which greatly limits the increase of individual numbers. In the present study, we computationally analyzed the repertoire of the cathelicidin (CATHL) family from the genome of forest musk deer and investigated their expression pattern by real-time PCR. Our results showed that the entire genome of forest musk deer encodes eight cathelicidins, including six functional genes and two pseudogenes. Phylogenetic analyses further revealed that all forest musk deer cathelicidin members have emerged before the split of the forest musk deer and cattle and that forest musk deer CATHL3L2 and CATHL9 are orthologous with two cattle pseudogenes. In addition, the gene expression results showed that the six functional genes are not only abundantly expressed in the spleen and lung, but are also differently expressed in response to abscesses, which suggests that forest musk deer cathelicidins may be involved in infections. Taken together, identification and characterization of the forest musk deer cathelicidins provide fundamental data for further investigating their evolutionary process and biological functions.
Thermal unequilibrium of strained black CsPbI3 thin films

Strain-stabilized perovskites The perovskite materials used for solar cells and light-emitting diodes (which are black in color) are generally less stable at room temperature than the electronically inactive nonperovskite phases (which are yellow in color). Steele et al. show that for CsPbI3, strain induced in a thin film after annealing the material to 330°C and then rapidly cooling it to room temperature kinetically trapped the black phase. Grazing-incidence wide-angle x-ray scattering revealed the crystal distortions and texture formation created by interfacial strain. Science, this issue p. 679 Interfacial clamping–induced biaxial strain can stabilize the black perovskite phase of CsPbI3 at room temperature. The high-temperature, all-inorganic CsPbI3 perovskite black phase is metastable relative to its yellow, nonperovskite phase at room temperature. Because only the black phase is optically active, this represents an impediment for the use of CsPbI3 in optoelectronic devices. We report the use of substrate clamping and biaxial strain to render black-phase CsPbI3 thin films stable at room temperature. We used synchrotron-based, grazing incidence, wide-angle x-ray scattering to track the introduction of crystal distortions and strain-driven texture formation within black CsPbI3 thin films when they were cooled after annealing at 330°C. The thermal stability of black CsPbI3 thin films is vastly improved by the strained interface, a response verified by ab initio thermodynamic modeling.
Long-Term Visual Outcomes for Small Uveal Melanoma Staged T1 Treated by Proton Beam Radiotherapy

There is increasing evidence of the survival benefit of treating uveal melanoma in an early stage, however it is important to discuss with the patient the associated risk of visual loss. We investigated visual outcomes for uveal melanomas staged T1 (T1UM) treated by proton beam radiotherapy (PBR) as a function of their distance to fovea-optic disc. This retrospective study included a cohort of 424 patients with T1UM treated with PBR between 1991 and 2010 with at least a 5-year follow-up. Visual acuity (VA) was analyzed for patients with posterior edge of tumor located at ≥3 mm (GSup3) or <3 mm (GInf3) from fovea-optic disc. The mean follow-up duration was 122 months, no tumor recurrence was observed. The mean baseline and final VA were 20/25 and 20/32 for GSup3 (n = 75), and 20/40 and 20/80 for GInf3 (n = 317) respectively. The frequency of a 20/200 or greater visual conservation was 93.2%(CI95%:87.7–99.1) and 60.1%(CI95%:54.9–65.9) for GSup3 and GInf3 respectively. This difference between groups was statistically significant (p < 0.001). The risk factors for significant VA loss (less than 20/200) were GInf3 location (p < 0.001), tumor touching optic disc (p = 0.04), initial VA inferior to 20/40 (p < 0.001), documented growth (p = 0.002), and age greater than 60 years (p < 0.001). In summary, PBR for T1UM yields excellent tumor control and good long-term visual outcomes for tumors located ≥3 mm from fovea-optic disc.
Development and Validation of the Praise, Indulgence, and Status Parenting Scale

Abstract The overarching aim of this study was to develop and validate a new scale (i.e., the Praise, Indulgence, and Status Parenting Scale [PISPS]) to measure modern parenting practices and behaviors consistent with instilling ideals of specialness (i.e., the notion that one is special), self-esteem, and status in children. In 2 studies on emerging adults (Study 1: N = 582, M age = 19.46; Study 2: N = 464, M age = 19.58), the PISPS was developed and validated using classical test theory (Study 1) and further refined using item–response theory (Study 2). Results from both studies indicated a 3-factor structure with factors differentially linked with correlates of interest including parenting strategies, self-esteem, narcissism, entitlement, and internalizing symptoms. Study 3 further validated the PISPS in a sample of parents (N = 638, M age = 35.79) reporting on their parenting and their child’s emotion regulation and symptoms of psychopathology. Overall, findings support the PISPS, its psychometric properties, and its unique contribution to child symptoms.
Early pregnancy reference intervals; 29 serum analytes from 4 to 12 weeks’ gestation in naturally conceived and uncomplicated pregnancies resulting in live births

Abstract Background Pregnancy introduces major physiological changes that also alter biochemical analytes. Maternal and perinatal health can be optimized by early intervention and therefore, pregnancy-specific reference intervals (RIs) for the local population are warranted. While the second and third trimester-specific changes are well described, the first trimester is less well characterized. We therefore wanted to facilitate early detection of abnormalities by generating first trimester reference values for 29 common analytes. Methods In a prospective early pregnancy (PEP) cohort (2016–2017), 203 pregnant women were recruited from 4 to 8 weeks’ gestation. Consecutive blood samples were drawn every 2 weeks until an ongoing second trimester pregnancy (n = 164) or a miscarriage (n = 39) occurred. After exclusion of women with complicated pregnancies or deliveries (n = 42), 122 women were included. The serum samples collected at <6, 6–8, 8–10, 10–12 and >12 weeks’ gestation were analyzed for 29 common analytes. Subsequently the RIs were calculated according to the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) recommendations (2.5–97.5th percentiles) and compared with the conventional RIs for non-pregnant women. Results Human chorionic gonadotropin (hCG), progesterone (P4), estradiol (E2), pregnancy-associated plasma protein A (PAPP-A), cancer antigen 125 (CA125), thyroid stimulating hormone (TSH), creatinine (CREA) and albumin (ALB) showed an early pregnancy-dependent change compared with conventional limits. For ALB the change was seen at 5.5 weeks’ gestation. Conclusions We report gestational age-specific RIs available from the early part of the first trimester applicable to everyday clinical care of pregnant women. Well-known alterations of RIs seen in later trimesters are also observed in the first.
The predictive values of serum dickkopf-1 and circulating tumor cells in evaluating the efficacy of transcatheter arterial chemoembolization treatment on hepatocellular carcinoma

Abstract In this study, we aim to explore the values of serum dickkopf-1 (DKK1) and circulating tumor cells (CTCs) in predicting the efficacy and prognosis of transcatheter arterial chemoembolization (TACE) treatment on patients with hepatocellular carcinoma (HCC). We did a retrospective analysis on 155 HCC patients who underwent TACE treatment. The patients were divided into response group (complete response and partial response) and nonresponse group (stable disease and progressive disease), and their changes in serum DKK1 and CTCs after TACE were recorded. Receiver operating characteristic curve and survival analysis were used to assess the predictive values of DKK1 and CTCs for TACE efficacy and long-term prognosis of HCC. We found that the levels of preoperative DKK1 and CTCs in patients with HCC had a moderate positive correlation (r = 0.54). After TACE treatment, the serum DKK1 and CTCs in the response group were significantly decreased compared to pretreatment levels (P < .05), whereas the nonresponse group showed significantly increased serum DKK1 and CTCs levels (P < .05). The largest area under the curve (AUC) was achieved when using >0.02 μg/L reduction in DKK1 level after 4 weeks of TACE to predict the efficacy of TACE treatment (AUC = 0.913, 95% confidence interval: 0.856–0.952, P < .001), with the sensitivity of 78.26% and the specificity of 88.07%. The overall survival, disease-free survival, and 5-year survival rates were all significantly lower in the patients with positive preoperative levels of serum DKK1 and CTCs. COX multivariate regression analysis showed that Eastern Cooperative Oncology Group score, and preoperative levels of serum DKK1 and CTCs are independent influencing factors for the prognosis of patients with HCC. Overall, our results demonstrated that serum DKK1 and CTCs levels were good biomarkers for predicting the efficacy and prognosis of TACE treatment in patients with HCC. Moreover, these parameters exhibited different characteristics, and might have different potential applications.
Young rural women’s perceptions of sexual infidelity among men in Cambodia

Abstract Marriage poses a high risk of HIV infection among Cambodian women due to the country’s double standards regarding extramarital sexual behaviour. Married men are much more likely than married women to engage in extramarital sex, and, among men, such activity is often socially and culturally condoned. Understanding the sexual beliefs young people possess is important as these beliefs may affect their future sexual behaviour and HIV-related risk. This study explored how young women in rural Cambodia conceptualise men’s extramarital affairs. Semi-structured, in-depth interviews were conducted in the Khmer language with 43 female high school students in three rural provinces. Thematic analysis was used to identify themes and sub-categories from the participants’ responses. Many participants accepted men’s infidelity and verbally supported traditional cultural beliefs and practices regarding male dominance within sex and relationships. They attributed their future husbands’ infidelity to their own behaviour and/or justified the act as a consequence of work-related mobility. Findings point to the need for new interventions as part of future HIV prevention programmes to increase their effectiveness among young Cambodian adults.
Immunotherapies for the Treatment of Uveal Melanoma—History and Future

Background: Uveal melanoma is the most common primary intraocular malignancy among adults. It is, nevertheless, a rare disease, with an incidence of approximately one case per 100,000 individuals per year in Europe. Approximately half of tumors will eventually metastasize, and the liver is the organ usually affected. No standard-of-care treatment exists for metastasized uveal melanoma. Chemotherapies or liver-directed treatments do not usually result in long-term tumor control. Immunotherapies are currently the most promising therapy option available. Methods: We reviewed both relevant recent literature on PubMed concerning the treatment of uveal melanoma with immunotherapies, and currently investigated drugs on ClinicalTrials.gov. Our own experiences with immune checkpoint blockers are included in a case series of 20 patients. Results: Because few clinical trials have been conducted for metastasized uveal melanoma, no definitive treatment strategy exists for this rare disease. The outcomes of most immunotherapies are poor, especially compared with cutaneous melanoma. However, encouraging results have been found for some very recently investigated agents such as the bispecific tebentafusp, for which a remarkably increased one-year overall survival rate, and similarly increased disease control rate, were observed in early phase studies. Conclusions: The treatment of metastatic uveal melanoma remains challenging, and almost all patients still die from the disease. Long-term responses might be achievable by means of new immunological strategies. Patients should therefore be referred to large medical centers where they can take part in controlled clinical studies.
White Matter Lesion Penumbra Shows Abnormalities on Structural and Physiologic MRIs in the Coronary Artery Risk Development in Young Adults Cohort

BACKGROUND AND PURPOSE: White matter lesions are 1 age-related manifestation of cerebrovascular disease, but subthreshold abnormalities have been identified in nonlesional WM. We hypothesized that structural and physiologic MR imaging findings of early cerebrovascular disease can be measured in middle-aged subjects in tissue adjacent to WM lesions, termed “penumbra. ” MATERIALS AND METHODS: WM lesions were defined using automated segmentation in 463 subjects, 43–56 years of age, from the Coronary Artery Risk Development in Young Adults (CARDIA) longitudinal observational cohort study. We described 0- to 2-mm and 2- to 4-mm-thick spatially defined penumbral WM tissue ROIs as rings surrounding WM lesions. The remaining WM was defined as distant normal-appearing WM. Mean signal intensities were measured for FLAIR, T1-, and T2-weighted images, and from fractional anisotropy, mean diffusivity, CBF, and vascular reactivity maps. Group comparisons were made using Kruskal-Wallis and pair-wise t tests. RESULTS: Lesion volumes averaged 0.738 ± 0.842 cm3 (range, 0.005–7.27 cm3). Mean signal intensity for FLAIR, T2, and mean diffusivity was increased, while T1, fractional anisotropy, and CBF were decreased in white matter lesions versus distant normal-appearing WM, with penumbral tissues showing graded intermediate values (corrected P < .001 for all group/parameter comparisons). Vascular reactivity was significantly elevated in white matter lesions and penumbral tissue compared with distant normal-appearing white matter (corrected P ≤ .001). CONCLUSIONS: Even in relatively healthy 43- to 56-year-old subjects with small white matter lesion burden, structural and functional MR imaging in penumbral tissue reveals significant signal abnormalities versus white matter lesions and other normal WM. Findings suggest that the onset of WM injury starts by middle age and involves substantially more tissue than evident from focal white matter lesions visualized on structural imaging.
Undernutrition and hyperandrogenism during pregnancy: Role in programming of cardiovascular disease and infertility

Maternal nutritional status programs the development of several systems in female offspring, with effects that depend on the severity, duration, and window of development when the nutritional perturbation is imposed. On the basis of the developmental origins of health and disease concept, we hypothesize that gestational low caloric intake may induce maternal subclinical hyperandrogenism during early pregnancy and compromise cardiovascular health and fertility in the female offspring. To examine this possibility, a literature search for human and animal studies was conducted using two electronic databases, PubMed and Cochrane until April 2019 to address the following questions: (a) Do androgens have a developmental role in cardiovascular and ovarian development? (b) Is excess maternal testosterone linked to cardiovascular disease and infertility? and (c) Could early pregnancy undernutrition enhance maternal androgen production and compromise health and fertility in female offspring? The observations reviewed, establish a potential causative link between maternal undernutrition and subclinical hyperandrogenism with hypertension and reduced ovarian reserve in the progeny. Further studies in appropriate models are needed to better understand whether low energy intake and subclinical maternal hyperandrogenism during early pregnancy can negatively affect the health of the female offspring.