Miracle-dz/UniFAR-FTUs huggingface dataset:
HIV stigma by association among Australian gay and bisexual men.

OBJECTIVE The negative effects of HIV stigma may extend beyond those who are HIV-positive, to people who are perceived to be at risk of HIV. This article examines HIV stigma by association among Australian gay and bisexual men (GBM). DESIGN Cross-sectional, online survey of 1280 Australian gay and bisexual men. This article focuses on HIV stigma from within a larger study that investigated stigma related to sexual identity. METHODS Bivariate and multivariable comparisons were made between men who experienced HIV stigma by association and those who did not. A serial mediation model was tested to investigate relationships between GBM community attachment, sexual identity stigma, HIV testing frequency, HIV stigma by association, psychological distress, and rejection of sex partners. RESULTS Results found that 5% of participants were HIV-positive, yet over 70% reported that they had been stigmatized by others for their perceived risk of acquiring HIV. Multivariable analysis indicated that HIV stigma by association was associated with more frequent HIV testing, greater GBM community attachment, experiencing stigma related to sexual identity and psychological distress. Our results suggest flow-on effects of HIV stigma by association, such as being more likely to reject other GBM on the basis of their HIV status or not testing for HIV. CONCLUSION Our results underscore the notion that HIV stigma can have broader, negative effects on HIV-affected populations. There is a need to address HIV stigma within GBM communities and society more broadly in order to encourage HIV testing and prevention among GBM.
Detection and Genetic Characterization of Puumala Orthohantavirus S-Segment in Areas of France Non-Endemic for Nephropathia Epidemica

Puumala virus (PUUV) in Europe causes nephropathia epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS). The incidence of NE is highly heterogeneous spatially, whereas the geographic distribution of the wild reservoir of PUUV, the bank vole, is essentially homogeneous. Our understanding of the processes driving this heterogeneity remains incomplete due to gaps in knowledge. Little is known about the current distribution and genetic variation of PUUV in the areas outside the well-identified zones of NE endemicity. We trapped bank voles in four forests in French regions in which NE is considered non-endemic, but sporadic NE cases have been reported recently. We tested bank voles for anti-PUUV IgG and characterized the S segment sequences of PUUV from seropositive animals. Phylogenetic analyses revealed specific amino-acid signatures and genetic differences between PUUV circulating in non-endemic and nearby NE-endemic areas. We also showed, in temporal surveys, that the amino-acid sequences of PUUV had undergone fewer recent changes in areas non-endemic for NE than in endemic areas. The evolutionary history of the current French PUUV clusters was investigated by phylogeographic approaches, and the results were considered in the context of the history of French forests. Our findings highlight the need to monitor the circulation and genetics of PUUV in a larger array of bank vole populations, to improve our understanding of the risk of NE.
Reproducibility of measurements on physical performance in head and neck cancer survivors; measurements on maximum mouth opening, shoulder and neck function, upper and lower body strength, level of physical mobility, and walking ability

Background Survivors of Head and Neck Cancer experience specific problems in functional performance. The aim of this study was to obtain the test-retest reliability of measurements on Maximal Mouth Opening (MMO), shoulder and neck function, lower and upper body strength, level of mobility and walking ability. Materials and methods Test-retest study design. Measurements on MMO (intra- and extra orally), Active range of motion of shoulders and neck, 30 Seconds Chair Stand Test, Grip Strength, Timed Up and Go test, and Six Minute Walk test. Results In total 50 participants were included. The mean age was 68.6. ± 9.9 years and median time since end of treatment was 3.0 years (Q1–Q3: 1.0–5.25 years). We found good to excellent test-retest reliability on the core set of measurements (Intraclass Correlation Coefficient (ICC) 0.77 to 0.98). Measurement of MMO with cardboard card, forward flexion shoulder and Six Minute Walk test had a relatively small measurement error (Smallest Detectable Change (SDC) % 5.4% - 15.1%). Measurement of MMO with a caliper, shoulder abduction, shoulder external rotation, later flexion and rotation of the neck, grip strength, 30 Seconds Chair Stand Test, and Timed up and Go test had a relatively large measurement error (SDC% 19.8% - 44.7%). Conclusion This core set of measurements on physical performance is found reliable and therefore able to differentiate in physical performance. The reported measurement errors should be taken into consideration when interpreting the results of repeated measurements. Implications for cancer survivors A core set of physical measurements can be used to measure physical performance in survivors of Head and Neck Cancer.
A novel sequence to improve auditory functional MRI with variable silent delays

Auditory functional MRI (fMRI) often uses silent inter‐volume delays for stimulus presentation. However, maintaining the steady‐state of the magnetization usually requires constant delays. Here, a novel acquisition scheme dubbed “pre‐Saturated EPI using Multiple delays in Steady‐state” (SEPIMS) is proposed, using spin saturation at a fixed delay before each volume to maintain steady‐state conditions, independent of previous spin history. This concept allows for variable inter‐volume delays and thus for flexible stimulus design in auditory fMRI. The purpose was to compare the signal stability of SEPIMS and conventional sparse EPI (CS‐EPI).
"I think it's been met with a shrug:" Oncologists' views toward and experiences with Right-to-Try.

BACKGROUND The federal Right-to-Try (RTT) Act created an alternate regulatory pathway for preapproval access to investigational drugs. A few studies have examined the experiences of physicians with Food and Drug Administration's Expanded Access Programs (EAP), but no study has yet to examine their attitudes and experiences toward RTT. METHODS This study explored the views of 21 oncologists at a major cancer center with 3 main sites across the U.S. using semi-structured interviews and qualitative analysis. Participants were selected to have experience with EAP. RESULTS Most oncologists had limited familiarity with RTT and several reported confusion about the legislation, including whether patients have a right to investigational drugs and an obligation for companies to provide them. While oncologists were interested in decreased regulatory burdens, three areas of concern were articulated: lack of safety and oversight; unclear structure and no provision for data collection; and potential heightening of patient expectations. Only four oncologists had experience discussing RTT and none formally attempted to obtain the drug through this mechanism. Participants questioned the practicality of RTT legislation and suggested alternative ways to improve access. CONCLUSIONS The study provides foundational empirical data underlying challenging ambiguities by experienced oncologists familiar with off-trial use of investigational therapeutics and reaffirms the role of physicians and regulatory bodies in mitigating the risks of investigational drugs. Our findings highlight the need for medical centers to inform oncologists about RTT and other preapproval pathways so that they are able to address questions from patients interested in non-trial investigational drugs.
The MEK/ERK Module Is Reprogrammed in Remodeling Adult Cardiomyocytes

Fetal and hypertrophic remodeling are hallmarks of cardiac restructuring leading chronically to heart failure. Since the Ras/Raf/MEK/ERK cascade (MAPK) is involved in the development of heart failure, we hypothesized, first, that fetal remodeling is different from hypertrophy and, second, that remodeling of the MAPK occurs. To test our hypothesis, we analyzed models of cultured adult rat cardiomyocytes as well as investigated myocytes in the failing human myocardium by western blot and confocal microscopy. Fetal remodeling was induced through endothelial morphogens and monitored by the reexpression of Acta2, Actn1, and Actb. Serum-induced hypertrophy was determined by increased surface size and protein content of cardiomyocytes. Serum and morphogens caused reprogramming of Ras/Raf/MEK/ERK. In both models H-Ras, N-Ras, Rap2, B- and C-Raf, MEK1/2 as well as ERK1/2 increased while K-Ras was downregulated. Atrophy, MAPK-dependent ischemic resistance, loss of A-Raf, and reexpression of Rap1 and Erk3 highlighted fetal remodeling, while A-Raf accumulation marked hypertrophy. The knock-down of B-Raf by siRNA reduced MAPK activation and fetal reprogramming. In conclusion, we demonstrate that fetal and hypertrophic remodeling are independent processes and involve reprogramming of the MAPK.
Development and validation of a six-RNA binding proteins prognostic signature and candidate drugs for prostate cancer

The dysregulation of RNA binding proteins (RBPs) play critical roles in the progression of several cancers. However, the overall functions of RBPs in prostate cancer (PCa) remain poorly understood. Therefore, we first identified 144 differentially expressed RBPs in tumors compared to normal tissues based on the TCGA dataset. Next, six RBP genes (MSI1, MBNL2, LENG9, REXO2, RNASE1, PABPC1L) were screened out as prognosis hub genes by univariate, LASSO and multivariate Cox regression and used to establish the prognostic signature. Further analysis indicated that high risk group was significantly associated with poor RFS, which was validated in the MSKCC cohort. Besides, patients in high risk group was closely associated with dysregulation of DNA damage repair pathway, copy number alteration, tumor burden mutation and low-respond to cisplatin (P < 0.001), bicalutamide (P < 0.001). Finally, three drugs (ribavirin, carmustine, carbenoxolone) were predicted using Connectivity Map. In summary, we identified a six-RBP gene signature and three candidate drugs against PCa, which may promote the individualized treatment and further improve the life quality of PCa patients.
Intranasal anti‐caspase‐1 therapy preserves myelin and glucose metabolism in a model of progressive multiple sclerosis

Inflammatory demyelination and axonal injury in the central nervous system (CNS) are cardinal features of progressive multiple sclerosis (MS), and linked to activated brain macrophage‐like cells (BMCs) including resident microglia and trafficking macrophages. Caspase‐1 is a pivotal mediator of inflammation and cell death in the CNS. We investigated the effects of caspase‐1 activation and its regulation in models of MS. Brains from progressive MS and non‐MS patients, as well as cultured human oligodendrocytes were examined by transcriptomic and morphological methods. Next generation transcriptional sequencing of progressive MS compared to non‐MS patients' normal appearing white matter (NAWM) showed induction of caspase‐1 as well as other inflammasome‐associated genes with concurrent suppression of neuron‐specific genes. Oligodendrocytes exposed to TNFα exhibited upregulation of caspase‐1 with myelin gene suppression in a cell differentiation state‐dependent manner. Brains from cuprizone‐exposed mice treated by intranasal delivery of the caspase‐1 inhibitor, VX‐765 or its vehicle, were investigated in morphological and molecular studies, as well as by fluorodeoxyglucose‐positron emission tomography (FDG‐PET) imaging. Cuprizone exposure resulted in BMC and caspase‐1 activation accompanied by demyelination and axonal injury, which was abrogated by intranasal VX‐765 treatment. FDG‐PET imaging revealed suppressed glucose metabolism in the thalamus, hippocampus and cortex of cuprizone‐exposed mice that was restored with VX‐765 treatment. These studies highlight the caspase‐1 dependent interactions between inflammation, demyelination, and glucose metabolism in progressive MS and associated models. Intranasal delivery of an anti‐caspase‐1 therapy represents a promising therapeutic approach for progressive MS and other neuro‐inflammatory diseases.
Optical Setup for Error Compensation in a Laser Triangulation System

Absolute distance measurement is a field of research with a large variety of applications. Laser triangulation is a well-tested and developed technique using geometric relations to calculate the absolute distance to an object. The advantages of laser triangulation include its simple and cost-effective setup with yet a high achievable accuracy and resolution in short distances. A main problem of the technology is that even small changes of the optomechanical setup, e.g., due to thermal expansion, lead to significant measurement errors. Therefore, in this work, we introduce an optical setup containing only a beam splitter and a mirror, which splits the laser into a measurement beam and a reference beam. The reference beam can then be used to compensate for different error sources, such as laser beam dithering or shifts of the measurement setup due to the thermal expansion of the components. The effectiveness of this setup is proven by extensive simulations and measurements. The compensation setup improves the deviation in static measurements by up to 75%, whereas the measurement uncertainty at a distance of 1 m can be reduced to 85 μm. Consequently, this compensation setup can improve the accuracy of classical laser triangulation devices and make them more robust against changes in environmental conditions.
Condom-vending machines in Italy: a qualitative exploration of gender differences to improve promotion and use

Abstract Objectives The purposes of this study were to explore gender differences in condom purchasing from condom-vending machines (CVMs) and identify ways to improve CVM promotion. Methods Semi-structured interviews with 42 men and women aged 18–50 years (mean ± standard deviation, 29.1 ± 7.9) and living in or near Florence, Italy, were conducted between May and June 2019. Techniques from expanded grounded theory-guided data analysis allowed for a constant comparative approach to contextualise data and identify emergent themes. Results Three themes emerged: (1) attitudes and barriers towards CVMs; (2) gender-specific purchasing influences and behaviours; and (3) CVM improvement and promotion. Women and men described varied concerns surrounding CVM purchasing, illuminating reasons for hesitancy. Focussing on CVM quality and improving product offerings were suggested by participants to increase use. Conclusion Findings offer practical recommendations to guide CVM messaging to increase access to and use of condoms and other personal care items. Men were cited as primary CVM users, expressing practical concerns surrounding CVMs, while, for women, CVM visibility was as much an advantage as a drawback. Reflecting consumer needs via diversified product offerings should be considered a priority for increased CVM use. Working to promote CVMs requires clear messaging that attends to gender norm limitations, details product safety and establishes CVMs as a reliable condom purchase outlet.
The Relationship between Poor Pulmonary Function and Irregular Pulse in the Elderly: Findings from a Nationwide Cross-Sectional Survey in Korea

Arrhythmia may be caused by reduced pulmonary function, and pulse palpation is a useful screening method for the early detection of cardiac arrhythmia. The aim of this study was to investigate the association between reduced pulmonary function and abnormal findings on pulse palpation in 2347 subjects aged ≥65 years using data from a nationwide survey. Pulse palpation was initially performed for 15 s and, if felt to be abnormal, it was performed again for 60 s. The prevalence of irregular pulse (IP) determined by the 60-second palpation was 61 (2.6%). The mean age of subjects with an IP was 73.0 (95% CI 71.7–74.3) years, and 45.8% were male. After adjustment for covariates, forced vital capacity (FVC)/predicted FVC, forced expiratory volume in one second (FEV1)/predicted FEV1, and the lowest FEV1 remained significant risk factors for IP. A restrictive or obstructive spirometry pattern was also an independent risk factor for IP. In summary, an IP is more prevalent when pulmonary function is reduced in the elderly, in whom careful pulse palpation may be necessary for the early detection of arrhythmia.
High‐gamma oscillations precede visual steady‐state responses: A human electrocorticography study

The robust steady‐state cortical activation elicited by flickering visual stimulation has been exploited by a wide range of scientific studies. As the fundamental neural response inherits the spectral properties of the gazed flickering, the paradigm has been used to chart cortical characteristics and their relation to pathologies. However, despite its widespread adoption, the underlying neural mechanisms are not well understood. Here, we show that the fundamental response is preceded by high‐gamma (55–125 Hz) oscillations which are also synchronised to the gazed frequency. Using a subdural recording of the primary and associative visual cortices of one human subject, we demonstrate that the latencies of the high‐gamma and fundamental components are highly correlated on a single‐trial basis albeit that the latter is consistently delayed by approximately 55 ms. These results corroborate previous reports that top‐down feedback projections are involved in the generation of the fundamental response, but, in addition, we show that trial‐to‐trial variability in fundamental latency is paralleled by a highly similar variability in high‐gamma latency. Pathology‐ or paradigm‐induced alterations in steady‐state responses could thus originate either from deviating visual gamma responses or from aberrations in the neural feedback mechanism. Experiments designed to tease apart the two processes are expected to provide deeper insights into the studied paradigm.
Effects of detraining on cardiorespiratory fitness of individuals with chronic stroke

ABSTRACT Background Aerobic training can improve cardiorespiratory fitness in individuals after stroke. However, the effects of short-term and long-term detraining are not well known. Objective To determine the effects of short-term (1-month) and long-term (6-month) detraining on cardiorespiratory fitness (VO2peak) of individuals after stroke, who participated in aerobic training. Methods A cohort study was developed. Twenty adults (57 ± 11 years old) with stroke were included. After completing an outpatient aerobic training, participants were divided into gain group (VO2peak increase >1.3 ml.kg−1.min−1 from before to immediately after the training) or non-gain group (VO2peak change ≤1.3 ml.kg−1.min−1). Cardiorespiratory fitness (VO2peak), obtained by the cardiopulmonary exercise test was assessed one and 6 months after the end of the training (short- and long-term detraining, respectively), or collected retrospectively from patient chart (before and after the training). Results There was found a significant interaction effect (time*group) for VO2peak (F= 6.108;p < 0,001). Higher values in the VO2peak observed in the gain group with the aerobic training (F = 25.86; p< .001) were significantly reduced with short-term detraining, reaching values similar to that observed before the training and to that of the non-gain group (F = 14.81;p= .001). Both groups had similar VO2peak values within long-term detraining (F = 2.70;p= .12), with no significant differences from the values observed before the training and after short-term detraining (0.11 ≤ p≤ 1.00). Conclusions Detraining on cardiorespiratory fitness of individuals after chronic stroke occurred within only 1 month. Therefore, it is important to maintain aerobic training throughout life.
Oncostatin M induces hyperalgesic priming and amplifies signaling of cAMP to ERK by RapGEF2 and PKA

Hyperalgesic priming is characterized by enhanced nociceptor sensitization by pronociceptive mediators, prototypically PGE2. Priming has gained interest as a mechanism underlying the transition to chronic pain. Which stimuli induce priming and what cellular mechanisms are employed remains incompletely understood. In adult male rats, we present the cytokine Oncostatin M (OSM), a member of the IL‐6 family, as an inducer of priming by a novel mechanism. We used a high content microscopy based approach to quantify the activation of endogenous PKA‐II and ERK of thousands sensory neurons in culture. Incubation with OSM increased and prolonged ERK activation by agents that increase cAMP production such as PGE2, forskolin, and cAMP analogs. These changes were specific to IB4/CaMKIIα positive neurons, required protein translation, and increased cAMP‐to‐ERK signaling. In both, control and OSM‐treated neurons, cAMP/ERK signaling involved RapGEF2 and PKA but not Epac. Similar enhancement of cAMP‐to‐ERK signaling could be induced by GDNF, which acts mostly on IB4/CaMKIIα‐positive neurons, but not by NGF, which acts mostly on IB4/CaMKIIα‐negative neurons. In vitro, OSM pretreatment rendered baseline TTX‐R currents ERK‐dependent and switched forskolin‐increased currents from partial to full ERK‐dependence in small/medium sized neurons. In summary, priming induced by OSM uses a novel mechanism to enhance and prolong coupling of cAMP/PKA to ERK1/2 signaling without changing the overall pathway structure.
An experimental philosophical bioethical study of how human rights are applied to clitorectomy on infants identified as female and as intersex

Abstract Clitorectomies performed on the genitals of infants identified as female and as intersex have been described both as similar procedures and as different procedures. The former types of surgery have been recognised more consistently as human rights abuses than the latter in recent decades. We tested social psychological explanations of why human rights are differently recognised when infants are described as ‘intersex’ or ‘female’; 122 laypeople in the UK read one of two near-identical descriptions of clitorectomies performed on intersex or female infants and reported their agreement with 22 items about the human rights of such infants. Clitorectomies were perceived as violating human rights more by women than by men, and more so when infants were described as female than intersex. Endorsement of human rights was better predicted by several psychological variables when infants were described as female than as intersex. Less politically conservative participants, as assessed by a Right-Wing Authoritarianism measure, and participants who trusted medical authority more recognised human rights violations of female infants more than intersex infants. Results are discussed with respect to human rights efforts to protect infants from medically non-necessary genital surgery on the basis of membership in identity categories or possession of sex characteristics.