bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is age and not antiretroviral therapy the strongest risk factor for chronic pain in HIV-infected population?
Authors: Kowalski Marcin , Horban Andrzej , Rongies Witold , Slomka Bartosz , Shahnazaryan Karen 
Published: January 2021

Abstract
Background. Chronic pain in HIV-infected patients on effective antiretroviral therapy (ART) limits patients’ normal functioning both somatically and psychologically. The current state of knowledge on the topic is insufficient, with the underlying causes of this pain unexplained. Therefore we analyzed the frequency and factors associated with chronic pain in HIV-infected patients on ART.Methods. We conducted a prospective, survey study, including consecutive HIV-infected patients under specialist care at the HIV Outpatient Clinic of the Hospital for Infectious Disease in Warsaw between February 2014 and December 2016. During their routine visit all patients who agreed to participate in the study were surveyed using a study questionnaire. For all patients reporting any pain the Brief Pain Inventory (BPI) form and Douleur Neuropathique 4 Questions form (DN4) were completed. Data on history and current ART and laboratory measurements were obtained from electronical database. Chi-squared and Kruskal-Wallis tests were used for group comparison. The potential factors associated with chronic pain were identified via logistic regression models. Results. In total 196 HIV-infected patients were included in the study, 57 (29,1%) of them reported chronic pain. The reported pain was mostly (75%) limited to a single area of the body. In univariable logistic regression model the odds of chronic pain were significantly higher with increasing age (OR 1.36 [95%CI:1.17-1.58]), time under specialist care (OR 2.25 [95%CI:1.42-35.7]), time on ART (OR2.96 [95%CI:1.60-5.49]), previous ART with zidovudine (OR 2.00[95%CI:1.06-1.55]) and previous treatment with ddI, ddC or d4T (OR4.13 [95%CI:1.92-8.91]). Homosexual route of HIV infection as compared to injecting drug use was decreasing the odds of chronic pain (OR0.33 [95%CI: 014-0.75]). In multivariable analyses, adjusting for all above the only factor associated with chronic pain was age (OR1.28 [95%CI:1.06-1.55]). Conclusions. The prevalence of chronic pain in the studied population of HIV-infected Polish patients was high. The only risk factor for chronic pain identified was age. With ageing HIV population it is therefore imperative to develop cooperation protocols for specialist HIV treatment clinics, pain treatment clinics, and rehabilitation units.
Challenges and opportunities associated with cervical cancer screening programs in a low income, high HIV prevalence context
Authors: Adedimeji Adebola Alade , Ajeh Rogers , Pierz Amanda , Nkeng Relindis , Nde Jackson Jr. , Fuhngwa Norbert , Nsame Denis , Nji Miriam , Dzudie Anastase , Anastos Kathryn M. , Castle Philip E. 
Published: January 2021

Abstract
Background Cervical cancer is a leading cause of death among Cameroon women. The burden of cervical cancer is in part traceable to the inadequate understanding of contextual determinants of access to expanding screening and prevention opportunities. We explored multilevel individual, community and structural factors that facilitate or inhibit cervical cancer prevention in women at risk in a high HIV prevalence context. Methods We utilized an exploratory qualitative approach to obtain data through focus group discussions and in-depth interviews from May to August, 2018. A two-stage systematic sampling strategy was used to select 80 women and 20 men who participated in 8 focus group discussions and 8 in-depth interviews. The socio-ecological model guided data analyses to identify micro-, meso-, and macro-level determinants of cervical cancer screening. Results Micro-level factors including lack of awareness and knowledge about cervical cancer, lack of access to information on and excessive costs for cervical cancer screening, low risk perceptions, and poor health seeking behaviors were major barriers for women seeking cervical cancer screening. Meso-level factors, such as social networks, socio-cultural norms, perceptions of the role of men and HIV-related stigma when screening is integrated into HIV care, also engender negative attitudes and behaviors. Macro-level barriers to cervical cancer screening included poorly equipped health facilities and a lack of national cancer prevention policies and programs. Conclusion In the context of the call for elimination of cervical cancer as a public health problem, our findings highlight challenges and opportunities that should be considered when implementing interventions to increase uptake of cervical cancer screening in low-middle income settings.
The Interactive Association between Sodium Intake, Alcohol Consumption and Hypertension among Elderly in Northern China: A Cross-sectional Study
Authors: Nan Xi , Lu Haiwen , Wu Jing , Xue Mingming , Qian Yonggang , Wang Wenrui , Wang Xuemei 
Published: January 2021

Abstract
Background: Hypertension is a worldwide public health problem. We sought to examine the interactive associations among sodium intake, alcohol consumption and hypertension among older adult residents of Inner Mongolia in northern China.Methods: This cross-sectional study used data from the National Survey for Nutrition and Adult Chronic Disease in Inner Mongolia. The prevalence of hypertension was age standardized by the direct method. Sodium intake and alcohol consumption were estimated using a weighing method and 24-hour recalls on 3 consecutive days. Hypertension was either self-reported or field-measured. Participants were categorized into six subgroups according to combinations of sodium intake status and drinking level. Logistic regression was used to determine the interactive effect of sodium intake and drinking on hypertension.Results: Of the 820 older adults who participated in this study, 523 (63.80%, age-standardized rate = 62.33%) had been diagnosed with hypertension. The mean sodium intake was 4.88 g. Sodium intake and drinking excessively were both independently related to higher risk of hypertension. A formal test for a multiplicative interaction between sodium intake and drinking revealed a significant interaction (p = 0.042), and the multivariable-adjusted odds ratio (95% CI) for the interaction was 1.1 (1.0–1.3). After adjusting for confounders, the risk of hypertension was highest among those with both excessive sodium intake and excessive alcohol consumption, with an odds ratio of 3.6 (95% CI: 1.7–7.9).Conclusions: The study highlights the interactive effect of sodium intake and alcohol consumption on hypertension. Primary health care providers should pay special attention to older adults with hypertension—especially those with an unhealthy diet including both excessive sodium and excessive alcohol intake. These findings are applicable for older adults in Inner Mongolia and worldwide.
Climate velocities and lagged species elevational shifts in mountain ranges
Authors: Shen Sheng-Feng , Chan Wei-Ping , Kuo Hung-Chi , Chen I-Ching 
Published: January 2021

Abstract
Mountain ranges support concentrations of climate-endangered endemic species, and are potential refugia for species retreating from the lowlands under anthropogenic climate change. Predicting the outcome for biodiversity requires knowledge of whether species are shifting uphill at the same rate as temperature isotherms (i.e. whether they are successfully tracking the velocity of climatic changes)1. Here, we provide a global assessment of the velocity of climate change in mountain ranges: applying thermal dynamic theory, deriving moist adiabatic lapse rates (MALR) using local surface temperature and water vapor. MALR varied substantially around the world, from 3 to 9°C cooling per km elevation increase. Consider the rate of terrestrial surface warming from 1971 to 2015, 24 regions can be identified as exhibiting high velocities where the isotherms have shifted more than one standard deviation of the global mean value (> 8.45 m yr-1). High velocities are typically found in relatively dry parts of the world, but also occur in wet regions with low lapse rates, such as in Northern Sumatra, Western Guiana Shield, Northern Andes, Costa Rica, Nepal, and Madagascar. Analysis of biodiversity data in relation to mountain-specific velocities revealed more cases of tracking between species and isotherms than previously suggested2 and more likely occurred at lower climate velocity. Nevertheless, upslope migrations of montane species have generally been lagging behind climate velocity. Such lags could continue to effect change even if the climate were to stabilize immediately. Reducing emissions would be expected to minimize lags, as well as slow the velocities of warming and required responses everywhere.
Closed-formed solutions of geometric albedos and phase curves of exoplanets for any reflection law
Authors: Heng Kevin , Morris Brett M. , Kitzmann Daniel 
Published: January 2021

Abstract
The albedo of a celestial body is the frac-tion of light reﬂected by it. Studying the albe-dos of the planets and moons of the Solar Sys-tem dates back at least a century [1, 2, 3, 4, 5]. Of particular interest is the relationship between the albedo measured at superior conjunction (full phase), known as the “geometric albedo”, and the albedo considered over all phase angles, known as the “spherical albedo” [2, 6, 7]. Modern astronom-ical facilities enable the measurement of geomet-ric albedos from visible/optical secondary eclipses [8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20] and the inference of the Bond albedo (spherical albedo measured over all wavelengths) from in-frared phase curves [21, 22, 23, 24, 25] of transit-ing exoplanets. Determining the relationship be-tween the geometric and spherical or Bond albe-dos usually involves complex numerical calculations [26, 27, 28, 29, 30, 31, 32] and closed-form solu-tions are restricted to simple reﬂection laws [33, 34]. Here we report the discovery of closed-form solu-tions for the geometric albedo and integral phase function that apply to any law of reﬂection. The integral phase function is used to obtain the phase integral, which is the ratio of the spherical to the geometric albedos. The generality of the solu-tions stems from a judicious choice of the coor-dinate system in which to perform diﬀerent parts of the derivation. The closed-formed solutions have profound implications for interpreting obser-vations. The shape of a reﬂected light phase curve and the secondary eclipse depth may now be self-consistently inverted to retrieve fundamental phys-ical parameters (single-scattering albedo, scatter-ing asymmetry factor, cloud cover). Fully-Bayesian phase curve inversions for reﬂectance maps and si-multaneous light curve detrending may now be per-formed, without the need for binning in time, due to the eﬃciency of computation. We demonstrate these innovations for the hot Jupiter Kepler-7b, inferring a revised geometric albedo of 0.12 ± 0.02, a Bond albedo of 0.18 ± 0.03 and a phase integral of 1.5 ± 0.1, which is consistent with isotropic scatter-ing. The scattering asymmetry factor is 0.04±0.15, implying that the aerosols are small compared to the wavelengths probed by the Kepler space tele-scope. In the near future, one may use the closed-form solutions discovered here to extract funda-mental parameters, across wavelength, from multi-wavelength phase curves of both gas-giant and ter-restrial exoplanets measured by the James Webb Space Telescope.
A Phase 2, Randomized Controlled Trial of Berberine Ursodeoxycholate (BUDCA) in Patients with Presumed Non-Alcoholic Steatohepatitis (NASH) and Type 2 Diabetes
Authors: Bisceglie Adrian Di , Harrison Stephen , Gunn Nadege , Kohli Anita , Liu Liping , Flyer Abbey , Goldkind Lawrence 
Published: January 2021

Abstract
Background & Aims: Non-alcoholic steatohepatitis (NASH) is frequently associated with obesity and diabetes and may lead to progressive liver disease although current treatment options are limited. Berberine ursodeoxycholate is an ionic salt of berberine and ursodeoxycholic acid, representing a new molecular entity that offers the possibility of combination therapy for NASH in a single treatment.Methods: A prospective, randomized, double-blind, placebo-controlled trial of two doses of berberine ursodeoxycholate administered orally was conducted in a cohort of 100 subjects with fatty liver disease and diabetes. Treatment was for 18 weeks and endpoints measured included reduction in liver fat content measured by MRI proton density fat fraction, improvement in glycemic control, changes in liver-associated enzymes, safety and tolerability.Results: Subjects that received 1000 mg twice a day of berberine ursodeoxycholate had significantly greater reduction in liver fat content compared to placebo (mean absolute decrease -4.8% vs. -2.0% [p=0.011], mean relative decrease -24.1 vs -8.3% [p=0.016]). Also, compared to placebo, subjects receiving this dose also experienced significant improvement in glycemic control as well as reductions in serum alanine aminotransferase and gamma glutamyl transferase activities. Serum lipid levels decreased modestly during therapy. The higher dose of berberine ursodeoxycholate was associated with an average weight loss (LS Mean) of -3.5kg compared to only -1.1kg with placebo (p=0.012). Diarrhea and abdominal discomfort were the most frequently reported adverse events. Conclusions: Berberine ursodeoxycholate is single molecule with a broad spectrum of metabolic activity in patients with presumed NASH and diabetes. It is relatively well tolerated and data from this phase 2 randomized controlled trial supportr its further development as a treatment for NASH with diabetes.
Validation of lipid-related therapeutic targets for coronary heart disease prevention using human genetics
Authors: Gordillo-Maranon Maria , Zwierzyna Magdalena , Charoen Pimphen , Drenos Fotios , Chopade Sandesh , Shah Tina , Engmann Jorgen , Casas Juan-Pablo , Chaturvedi Nishi , Papacosta Olia , Wannamethee Goya , Wong Andrew , Sofat Reecha , Kivimaki Mika , Price Jackie , Hughes Alun , Gaunt Tom , Lawlor Debbie , Gaulton Anna , Hingorani Aroon , Schmidt Amand , Finan Chris 
Published: January 2021

Abstract
Drug target Mendelian randomization (MR) studies use DNA sequence variants in or near a gene encoding a drug target, that alter its expression or function, as a tool to anticipate the effect of drug action on the same target. Here, we applied MR to prioritize drug targets for their causal relevance for coronary heart disease (CHD). The targets were further prioritized using genetic co-localization, protein expression profiles from the Human Protein Atlas and, for targets with a licensed drug or an agent in clinical development, by sourcing data from the British National Formulary and clinicaltrials.gov. Out of the 341 drug targets identified through their association with circulating blood lipids (HDL-C, LDL-C and triglycerides), we were able to robustly prioritize 30 targets that might elicit beneficial treatment effects in the prevention or treatment of CHD. The prioritized list included NPC1L1 and PCSK9, the targets of licensed drugs whose efficacy has been already proven in clinical trials. To conclude, we discuss how this approach can be generalized to other targets, disease biomarkers and clinical end-points to help prioritize and validate targets during the drug development process.
Effect of The CRADLE Vital Signs Alert Device Intervention on Referrals for Obstetric Haemorrhage in Low-Middle Income Countries: A Secondary Analysis of A Stepped-Wedge Cluster-Randomised Control Trial
Authors: Giblin Lucie , Vousden Nicola , Nathan Hannah , Gidiri Muchabayiwa Francis , Goudar Shivaprasad , Sandall Jane , Seed Paul , Chappell Lucy , Shennan Andrew 
Published: January 2021

Abstract
Background Obstetric haemorrhage is the leading cause of maternal death worldwide, 99% of which occur in low and middle income countries. The majority of deaths and adverse events are associated with delays in identifying compromise and escalating care. Management of severely compromised pregnant women may require transfer to tertiary centres for specialised treatment, therefore early recognition is vital for efficient management. The CRADLE vital signs alert device accurately measures blood pressure and heart rate, calculates the shock index (heart rate divided by systolic blood pressure) and alerts the user to compromise through a traffic light system reflecting previously validated shock index thresholds. Methods This is a planned secondary analysis of data from the CRADLE-3 trial from ten clusters across Africa, India and Haiti where the device and training package were randomly introduced. Referral data were prospectively collected for a 4-week period before, and a 4-week period 3 months after implementation. Referrals from primary or secondary care facilities to higher level care for any cause were recorded. The denominator was the number of women seen for maternity care in these facilities. Results Between April 1 2016 and Nov 30th, 2017 536 223 women attended maternity care facilities. We reviewed a total of 144 cases that were referred, 119 cases 3.84% pre-implementation and 4.48% post-implementation were referred to higher-level facilities. Overall referrals did not significantly reduce (OR 0.89 (0.39- 2.05)) but there was a significant reduction in referrals for bleeding (OR 0.5 (0.39-0.65) following introduction of the device, with homogeneity (I-squared 10.4) between sites. There was no increase in any bleeding-related morbidity.Conclusions Referrals for obstetric haemorrhage reduced following implementation of the CRADLE Vital Signs Alert Device, occurring without an increase in maternal death or emergency hysterectomy. This demonstrates the potential benefit of Shock Index in management pathways for obstetric haemorrhage and targeting limited resources in low- middle- income settings. Trial Registration This study is registered with the ISRCTN registry, number ISRCTN41244132 (02/02/2016)
Structural basis for small molecule targeting of
Doublecortin Like Kinase 1 DCLK1
Authors: Patel Onisha , Roy Michael , Kropp Ashleigh , Dai Weiwen , Lucet Isabelle 
Published: January 2021

Abstract
Doublecortin-like kinase 1 (DCLK1) is a bi-functional protein classified as a Microtubule-Associated Protein (MAP) and as a serine/threonine kinase that plays a critical role in regulating microtubule assembly. This understudied kinase is upregulated or mutated in a wide range of cancers. Knockdown studies have shown that DCLK1 is functionally important for tumour growth. However, the presence of tissue and development specific spliced DCLK1 isoforms and the lack of systematic evaluation of their biological function have challenged the development of effective strategies to understand the role of DCLK1 in oncogenesis. Recently, DCLK1-IN-1 was reported as a potent and selective DCLK1 kinase inhibitor, a powerful new tool to dissect DCLK1 biological functions.
Here, we report the crystal structures of DCLK1 kinase domain in complex with two DCLK1-IN-1 precursors and DCLK-IN-1. Combined, our structural data analysis illuminates and rationalises the structure-activity relationship that informed development of DCLK1-IN-1 and provides the basis for DCLK1-IN-1 increased selectivity. We show that DCLK1-IN-1 induces a drastic conformational change of the N-lobe, which uncovered a new allosteric site. In addition, we demonstrate that DCLK1-IN-1 binds DCLK1 long isoforms with high affinity but does not prevent DCLK1 MAP function. Together, our work outlines the need for in-depth studies to rationally design of isoform-specific modulators and provides an invaluable structural platform to further the design of selective DCLK1 therapeutic agents.
Risk Factors for Severe Illness and Death in COVID-19: A Systematic Review and Meta-analysis
Authors: Degarege Abraham , Naveed Zaeema , Kabayundo Josiane , Brett-Major David 
Published: January 2021

Abstract
Objectives This systematic review and meta-analysis synthesized the evidence on the impact of demographics and comorbidities with clinical outcomes of COVID-19, including severe illness, admission to the intensive care unit (ICU), and death.MethodsThe PRISMA guidelines were followed to conduct and report this meta-analysis. The protocol is registered in PROSPERO International prospective register of systematic reviews (ID=CRD42020184440). Two authors independently searched literature from PubMed, Embase, Cochrane library and CINHAL on May 6, 2020; removed duplicates; screened titles, abstracts and full text using criteria; and extracted data from eligible articles. A random-effects model was used to estimate the summary odds ratio (OR). Variations among studies were examined using Cochrane Q and I2.ResultsOut of 4,275 articles obtained from the databases and screened, 71 studies that involved 216,843 patients were abstracted and then, where appropriate, analyzed by meta-analysis. The COVID-19 related outcomes reported were death in 26 studies, severe illness in 41 studies, and admission to ICU in 11 studies. Death was significantly correlated with hypertension (OR 2.60, 95% CI 1.95–3.25, I2 = 52.6%, n= 13 studies), cardiovascular disease (5.16, 4.10–6.22, 0.0%, 6), diabetes (2.11, 1.35–2.87, 67.4%, 12), chronic respiratory disease (2.83, 2.14–3.51, 0.0%, 9), cerebrovascular diseases (5.14, 1.08–9.19, 0.0%, 2), male sex (1.34, 1.18 – 1.50, 38.7%, 16), age older than 60 (6.09, 3.53 – 8.66, 95.5%, 6) or 65 years (3.56, 1.21 – 5.90, 18.2%, 6). Severe illness was also significantly associated with hypertension (1.70, 1.30 –2.10, 47.8%, 21), cardiovascular diseases (2.04, 1.01–3.08, 30.6%, 10), diabetes (1.65, 1.23–2.08, 24.9%, 18), male sex (1.35, 1.23 – 1.47, 0.0%, 32) and age at least 60 (4.91, 1.35 – 8.47, 0.0%, 4) or 65 (2.55,1.94 – 3.17, 24.5%, 9) years. Among hospitalized patients, the odds of admission to ICU was greater in individuals who had cardiovascular diseases (1.36,1.04–1.69, 0.0%, 4), diabetes (1.55, 1.20–1.90, 0.0%, 5) and chronic respiratory disease (1.52, 1.09–1.94, 0.0%, 5) than those who were not having these comorbidities. ConclusionsOlder age and chronic diseases increase the risk of developing severe illness, admission to ICU and death among COVID-19 patients. Special strategies are warranted to prevent SARS-CoV-2 infection and manage COVID-19 cases in those with vulnerabilities.