bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time trends in socio-economic inequalities in HIV testing: insights from population-based surveys in 16 sub-Saharan African countries
Authors: Ante-Testard Pearl Anne , Benmarhnia Tarik , Bekelynck Anne , Baggaley Rachel , Ouattara Eric , Temime Laura , Jean Kévin 
Published: October 2019

SummaryBackgroundOverall increase in the uptake of HIV testing in the past decades may hide discrepancies across socio-economic groups. We used population-based surveys conducted in sub-Saharan Africa to quantify socio-economic inequalities in recent HIV testing uptake, together with their trends over the two past decades.MethodsWe analyzed the data from Demographic and Health Surveys in sub-Saharan African countries where at least one survey was conducted before and after 2008. Country- and gender-specific proportions of recent (<12 month) HIV testing were assessed across wealth and education groups, and inequalities were quantified using the relative and slope indices of inequalities. Time trends in inequalities were assessed and results were pooled across countries using random-effect meta-analyses.FindingsWe analyzed data from 32 surveys conducted between 2003 and 2016 in 16 countries among 537,784 participants. In pre-2008 surveys, women reported higher HIV testing uptake than men in 8 out of 16 countries, and in 15 out of 16 countries in post-2008 surveys. After 2008, the wealthiest women were on average 2.77 (95% CI 1.42-5.40) times more likely to report recent testing than the poorest; and 3.55 (1.85-6.81) times in men. The averaged absolute difference in recent testing between the richest and poorest was 11.1 (4.6-17.5) percentage points in women and 15.1 (9.6-20.6) in men. Over time, relative inequalities in recent HIV testing decreased in both genders, while absolute inequalities plateaued in women and increased in men.InterpretationsThe overall increase in HIV testing uptake that was stimulated by the impetus to scale up HIV treatment in sub-Saharan Africa led to a decrease in relative inequalities, while absolute inequalities persisted. Within most countries, large inequalities still remained, both in absolute and relative scales, especially in West and Central Africa. A greater focus should be put on equity in monitoring HIV testing programs.A French version of this article is available in the Appendices [Une version française de cet article est disponible en appendice].FundingINSERM-ANRS (France Recherche Nord & Sud Sida-HIV Hépatites), grant number ANRS-12377.
Short-term mental health sequelae of bereavement predict long-term physical health decline in older adults: US Health and Retirement Study Analysis
Authors: Domingue Benjamin W. , Duncan Laramie , Harrati Amal , Belsky Daniel W. 
Published: October 2019

AbstractObjectiveDeath of a spouse is a common late-life event with mental- and physical-health sequelae. Whereas mental-health sequelae of spousal death tend to be transient, physical-health sequelae may persist, leading to disability and mortality. Growing evidence linking poor mental health to aging-related disease suggests the hypothesis that transient poor mental health following death of a spouse could be a harbinger of physical health decline. If so, identification of bereavement-related mental health symptoms could provide an opportunity for prevention.MethodsWe analyzed data from N=35,103 individuals followed from 1994-2014 in the US Health and Retirement Study (HRS) and identified N=4,629 who were widowed during follow-up. We tested change in mental and physical health from pre-bereavement through the 5-year period following spousal death.ResultsBereaved spouses experienced an immediate increase in depressive symptoms following their spouses’ deaths but the depressive shock attenuated within one year. Bereaved spouses also experienced increases in disability, chronic-disease morbidity, and hospitalization, which grew in magnitude with time since spousal death, especially among older HRS participants. Bereaved spouses were at increased risk of death compared to HRS participants who were not bereaved. The magnitude of depressive symptoms in the immediate aftermath of spousal death predicted physical-health decline and mortality risk over 5 years of follow-up.ConclusionsBereavement-related depressive symptoms provide an indicator of risk for physical health decline and death in older adults. Screening for depressive symptoms in bereaved older adults may represent an opportunity for intervention to preserve healthy lifespan.Plain Language SummaryThe clinical significance of depressive symptoms during bereavement for long-term health is not well understood. We analyzed longitudinal data tracking mental and physical health of more than 4,000 older adults who were widowed during follow-up. Widows and widowers who experienced more severe depressive symptoms immediately following their spouse’s death were at increased risk for incident disability, chronic disease, hospitalization, and mortality over the five years following their spouse’s death. Transient depressive symptoms related to bereavement may provide a clinical indicator of risk for long-term physical health decline in older adults. Findings motivate increased integration of psychiatric assessment in geriatric care.
Awareness and knowledge of interventional radiology among medical students at an Indian institution
Authors: Agrawal Deepsha , Renfrew Michael Alan , Singhal Sulove , Bhansali Yash 
Published: October 2019

PurposeInterventional radiology (IR) is a novel and evolving sub-specialty that encompasses image guided diagnostic and therapeutic procedures. With the advent of new imaging techniques and an increasing demand of minimally invasive procedures IR continues to grow as a core component in medical and surgical therapeutics. Radiology teaching is a part of medical undergraduate curriculum, however, the medical undergraduate cohort lacks exposure to IR principles, methods and techniques.The purpose of this study is to determine the knowledge and awareness of IR among medical students in a single university in India.Materials and MethodsAnonymous electronic surveys were sent to 350 medical students of Pt. JNM Medical College, Raipur, India. Each survey comprised of questions assessing knowledge and exposure to IR. A total of 70 students (20%) responded.Results85.7% of respondents believed that radiologists have a role in diagnostic as well as therapeutic interventions, however, 60% of students cited a very poor/poor knowledge of IR. A larger part, 91.5%, stated that they would be interested in IR based teaching delivered as a part of their undergraduate teaching program. Those who knew at least one interventional radiology technique were 1.51 (95% CI: 1.02 - 2.22; p < 0.05) times more likely to consider it as a career.ConclusionMedical Students demonstrate a poor knowledge of IR. This corresponds to a limited and inconsistent exposure to IR in medical schools. The study suggests that there is a need to deliver an IR based curriculum in medical undergraduate teaching in India.
The Impact of Scaling up Dolutegravir on Antiretroviral Resistance in South Africa
Authors: Hauser Anthony , Kusejko Katharina , Johnson Leigh F. , Günthard Huldrych F. , Riou Julien , Wandeler Gilles , Egger Matthias , Kouyos Roger D. 
Published: October 2019

AbstractBackgroundRising resistance of HIV-1 to non-nucleoside reverse transcriptase inhibitors (NNRTIs) threatens the success of the global scale-up of antiretroviral therapy (ART). The switch to WHO-recommended dolutegravir (DTG)-based regimens could reduce this threat due to DTG’s high genetic barrier to resistance. We used mathematical modelling to examine the impact of the scale-up of DTG-based ART on NNRTI pre-treatment drug resistance (PDR) in South Africa, 2019-2040.Methods and resultsWe adapted the MARISA (Modelling Antiretroviral drug Resistance In South Africa) model, an epidemiological model of the transmission of NNRTI resistance in South Africa. We modelled the introduction of DTG in 2019 under two scenarios: DTG as first-line regimen for ART-initiators, or DTG for all patients, including patients on suppressive NNRTI-based ART. Due to safety concerns related to DTG during pregnancy, we assessed the impact of prescribing DTG to all men and in addition to i) women beyond reproductive age, ii) women beyond reproductive age or using contraception, and iii) all women. The model projections show that, compared to the continuation of NNRTI-based ART, introducing DTG would lead to a reduction in NNRTI resistance in all scenarios if both ART initiators are started on a DTG-based regimens and those on NNRTI-based regimens are rapidly switched to DTG. NNRTI resistance would continue to increase if DTG-based ART was restricted to men. When given to all men and women, DTG-based ART could reduce the level of NNRTI resistance from 58.5% (without DTG) to 14.8% (with universal DTG) in 2040. If all men and women beyond reproductive age or on contraception are started on or switched to DTG-based ART, NNRTI resistance would reach 35.1% in 2040.ConclusionsOur model shows the potential benefit of scaling up DTG-based regimens for halting the rise of NNRTI resistance. Starting or switching all men and women to DTG would lead to a sustained decline in resistance levels whereas using DTG-based ART in all men, or in men and women beyond childbearing age, would slow down the increase in levels of NNRTI resistance.
Cohort profile: The International epidemiology Databases to Evaluate AIDS (IeDEA) in sub-Saharan Africa, 2012-2019
Authors: Chammartin Frédérique , Dao Ostinelli Cam Ha , Anastos Kathryn , Jaquet Antoine , Brazier Ellen , Brown Steven , Dabis François , Davies Mary-Ann , Duda Stephany N , Malateste Karen , Nash Denis , Wools-Kaloustian Kara K , von Groote Per M , Egger Matthias 
Published: October 2019

ABSTRACTPurposeThe objectives of the International epidemiology Databases to Evaluate AIDS (IeDEA) are to (i) evaluate the delivery of combination antiretroviral therapy (ART) in children, adolescents and adults in sub-Saharan Africa, (ii) to describe ART regimen effectiveness, durability and tolerability, (iii) to examine HIV-related comorbidities and co-infections, and (iv) to examine the pregnancy- and HIV-related outcomes of women on ART and their infants exposed to HIV or antiretroviral therapy in utero or via breastmilk.ParticipantsIeDEA is organized in four regions (Central, East, Southern and West Africa), with 240 treatment and care sites, six data centres at African, European and US universities, and almost 1.4 million children, adolescents and adult people living with HIV (PLWHIV) enrolled.Findings to dateThe data include socio-demographic characteristics, clinical outcomes, opportunistic events, treatment regimens, clinic visits and laboratory measurements. They have been used to analyse outcomes in people living with HIV-1 or HIV-2 who initiate ART, including determinants of mortality, of switching to second-line and third-line ART, drug resistance, loss to follow-up and the immunological and virological response to different ART regimens. Programme-level estimates of mortality have been corrected for loss to follow-up. We examined the impact of co-infection with hepatitis B and C, and the epidemiology of different cancers and of (multi-drug resistant) tuberculosis, renal disease and of mental illness. The adoption of “Treat All”, making ART available to all PLWHIV regardless of CD4+ cell count or clinical stage was another important research topic.Future plansIeDEA has formulated several research priorities for the “Treat All” era in sub-Saharan Africa. It recently obtained funding to set up sentinel sites where additional data are prospectively collected on cardiometabolic risks factors as well as mental health and liver diseases, and is planning to create a drug resistance database.
The Pan-Cancer Landscape of Prognostic Germline Variants in 10,582 Patients
Authors: Chatrath Ajay , Przanowska Roza , Kiran Shashi , Su Zhangli , Saha Shekhar , Wilson Briana , Tsunematsu Takaaki , Ahn Ji-Hye , Lee Kyung Yong , Paulsen Teressa , Sobierajska Ewelina , Kiran Manjari , Tang Xiwei , Li Tianxi , Kumar Pankaj , Ratan Aakrosh , Dutta Anindya 
Published: October 2019

AbstractWhile clinical data provides physicians with information about patient prognosis, genomic data can further improve these predictions. We analyzed sequencing data from over 10,000 cancer patients and identified hundreds of prognostic germline variants using multivariate Cox regression models. These variants provide information about patient outcomes beyond clinical information currently in use and may augment clinical decisions based on expected tumor aggressiveness. Molecularly, at least twelve of the germline variants are likely associated with patient outcome through perturbation of protein structure and at least five through association with gene expression differences. About half of these germline variants are in previously reported tumor suppressors or oncogenes, with the other half pointing to loci of previously unstudied genes in the literature that should be further investigated for roles in cancers. Our results suggest that germline variation contributes to tumor progression across most cancers and contains patient outcome information not captured by clinical factors.
Defective Nucleotide Catabolism Defines a Subset of Cancers Sensitive to Purine Nucleoside Phosphorylase Inhibition
Authors: Abt Evan R. , Lok Vincent , Le Thuc M. , Poddar Soumya , Kim Woosuk , Capri Joseph R. , Abril-Rodriguez Gabriel , Czernin Johannes , Donahue Timothy R. , Mehrling Thomas , Ribas Antoni , Radu Caius G. 
Published: October 2019

ABSTRACTSmall molecule inhibitors of purine nucleoside phosphorylase (PNP) have been explored as a treatment strategy for leukemia and lymphoma, however, the determinants of response to this class of drugs are incompletely understood. PNP inhibitors impair cell proliferation by preventing catabolism of the nucleoside deoxyguanosine (dG) which induces toxic imbalances amongst intracellular deoxyribonucleotide triphosphate (dNTP) pools following its phosphorylation and trapping by nucleoside kinases. We hypothesized that differential nucleoside uptake or catabolism defines cancer cell lines as either sensitive or resistant to PNP inhibition. Among cancer cell lines we found that T-cell acute lymphoblastic leukemia (T-ALL) cells are uniquely and acutely sensitive to PNP inhibition whereas the B-cell leukemia and solid tumor models are completely resistant. We determined that although the nucleoside scavenging kinase deoxycytidine kinase (dCK) was active in all cells tested, PNP inhibitors only induced dGTP pool increases in sensitive models. By evaluating the expression of key genes involved in nucleotide scavenging, biosynthesis, and phosphohydrolysis in a panel of sensitive and resistant cell lines we found that the dNTP phosphohydrolase SAM histidine aspartate containing protein 1 (SAMHD1) was exclusively expressed in resistant models. Using CRISPR/Cas9 SAMHD1 knockout cell lines, we verified that PNP inhibitor sensitivity is a function of SAMHD1 expression and determined that the pharmacological inhibition of dCK or genetic restoration of SAMHD1 conferred resistance to PNP inhibition. Importantly, we determined that low expression of SAMHD1 is not limited to T-ALL as subset of established and primary solid tumors models are SAMHD1-deficient. These solid tumor models were consistently acutely sensitive to PNP inhibitors which indicates that the utility of PNP inhibitors extends beyond hematological malignancies. Additionally, we found that deoxycytidine (dC) can limit the anti-proliferative effects of PNP inhibitors by competing with dG for phosphorylation by dCK but this effect can be overcome by expression of dC-catabolizing gene cytidine deaminase (CDA). Collectively, these results indicate that SAMHD1, dCK and CDA are critical biomarkers that must be used to stratify patients in clinical trials evaluating pharmacological PNP inhibition.
Representation of Visual Landmarks in Retrosplenial Cortex
Authors: Fischer Lukas F. , Soto-Albors Raul Mojica , Buck Friederike , Harnett Mark T. 
Published: October 2019

AbstractThe process by which visual information is incorporated into the brain’s spatial framework to represent landmarks is poorly understood. Studies in humans and rodents suggest that retrosplenial cortex (RSC) plays a key role in these computations. We developed an RSC-dependent behavioral task in which head-fixed mice learned the spatial relationship between visual landmark cues and hidden reward locations. Two-photon imaging revealed that these cues served as dominant reference points for most task-active neurons and anchored the spatial code in RSC. Presenting the same environment but decoupled from mouse behavior degraded encoding fidelity. Analyzing visual and motor responses showed that landmark codes were the result of supralinear integration. Surprisingly, V1 axons recorded in RSC showed similar receptive fields. However, they were less modulated by task engagement, indicating that landmark representations in RSC are the result of local computations. Our data provide cellular- and network-level insight into how RSC represents landmarks.
N-terminal protein acetylation by NatB modulates the levels of Nmnats, the NAD+biosynthetic enzymes inSaccharomyces cerevisiae
Authors: Croft Trevor , Venkatakrishnan Padmaja , James Theoga Raj Christol , Groth Benjamin , Cater Timothy , Lin Su-Ju 
Published: October 2019

ABSTRACTNAD+is an essential metabolite participating in cellular biochemical processes and signaling. The regulation and interconnection among multiple NAD+biosynthesis pathways are not completely understood. We previously identified the N-terminal (Nt) protein acetyltransferase complex NatB as a NAD+homeostasis factor. Cells lacking NatB show an approximate 50% reduction in the NAD+level and aberrant metabolism of NAD+precursors, which are associated with a decrease of nicotinamide mononucleotide adenylyltransferases (Nmnat) protein levels. Here we show this decrease in NAD+and Nmnat protein levels is specifically due to the absence of Nt-acetylation of Nmnat (Nma1 and Nma2) proteins, and not other NatB substrates. Nt-acetylation is a critical regulator of protein degradation by the N-end rule pathways, indicating absence of Nt-acetylation may alter Nmnat protein stability. Interestingly, the rate of protein turnover (t1/2) of non-Nt-acetylated Nmnats does not significantly differ from Nt-acetylated Nmnats, suggesting reduced Nmnat levels in NmatB mutants are not due to increased post-translational degradation of non-Nt-acetylated Nmnats. In line with these observations, deletion or depletion of N-rule pathway ubiquitin E3 ligases in NatB mutants is not sufficient to restore NAD+levels. Moreover, the status of Nt-acetylation does not alter the rate of translation initiation of Nmnats. Collectively our studies suggest absence of Nt-acetylation may increase co-translational degradation of nascent Nmnat polypeptides, which results in reduced Nmnat levels in NatB mutants. Nmnat activities are essential for all routes of NAD+biosynthesis. Understanding the regulation of Nmnat protein homeostasis will facilitate our understanding of the molecular basis and regulation of NAD+metabolism.
Novel regulation from novel interactions: Identification of an RNA sponge that controls the levels, processing and efficacy of the RoxS riboregulator of central metabolism inBacillus subtilis
Authors: Durand Sylvain , Callan-Sidat Adam , McKeown Josie , Li Stephen , Kostova Gergana , Hernandez-Fernaud Juan R. , Alam Mohammad Tauqeer , Millard Andrew , Constantinidou Chrystala , Condon Ciarán , Denham Emma L. 
Published: October 2019

ABSTRACTSmall RNAs (sRNAs) are a taxonomically-restricted but transcriptomically-abundant class of post-transcriptional regulators. While potentially of importance, we know the function of few. This is in no small part because we lack global-scale methodology enabling target identification, this being especially acute in species without known RNA meeting point proteins (e.g. Hfq). We apply a combination of psoralen RNA cross-linking and Illumina-sequencing to identify RNA-RNA interacting pairsin vivoinBacillus subtilis, resolving previously well-described interactants. Although sRNA-sRNA pairings are rare (compared with sRNA/mRNA), we identify a robust example involving the unusually conserved sRNA (RoxS/RsaE) and an unstudied sRNA that we term Regulator of small RNA A (RosA). This interaction is found in independent samples across multiple conditions. Given the possibility of a novel associated regulatory mechanism, and the rarity of well-characterised bacterial sRNA-sRNA interactions, we mechanistically dissect RosA and its interactants. RosA we show to be a sponge RNA, the first to be described in a Gram-positive bacterium. RosA interacts with at least two sRNAs, RoxS and FsrA. Unexpectedly, it acts differently on each. As expected of a sponge RNA, FsrA is sequestered by RosA. The RosA/RoxS interaction is more complex affecting not only the level of RoxS but also its processing and efficacy. Importantly, RosA provides the condition-dependent intermediary between CcpA, the key regulator of carbon metabolism, and RoxS. This not only provides evidence for a novel, and functionally important, regulatory mechanism, but in addition, provides the missing link between transcriptional and post-transcriptional regulation of central metabolism.
Timing matters: The temporal representation of experience in subjective mood reports
Authors: Keren Hanna , Zheng Charles , Jangraw David C. , Chang Katharine , Vitale Aria , Nielson Dylan , Rutledge Robb B. , Pereira Francisco , Stringaris Argyris 
Published: October 2019

AbstractHumans refer to their own mood state regularly in day-to-day as well as in clinical interactions. Theoretical accounts suggest that when reporting on our mood we integrate over the history of our experiences; yet, the temporal structure of this integration remains unexamined. Here we use a computational approach to quantitatively answer this question and show that early events exert a stronger influence on the reported mood compared to recent events. We show that a Primacy model accounts better for mood reports compared to a range of alternative temporal representations, and replicate this result across random, consistent or dynamic structures of reward environments, age groups and both healthy and depressed participants. Moreover, we find evidence for neural encoding of the Primacy, but not the Recency, model in frontal brain regions related to mood regulation. These findings hold implications for the timing of events in experimental or clinical settings and suggest new directions for individualized mood interventions.SignificanceHow we rate our own mood at any given moment is shaped by our experiences; but are the most recent experiences the most influential, as assumed by current theories? Using several sources of experimental data and mathematical modeling, we show that earlier experiences within a context are more influential than recent events, and replicate this finding across task environments, age groups, and in healthy and depressed participants. Additionally, we present neural evidence supporting this primacy model. Our findings show that delineating a temporal structure is crucial in modeling mood and this has key implications for its measurement and definition in both clinical and everyday settings.