bluuebunny/crossref_metadata_2025_split huggingface dataset:
Androgen‐dependent miR‐125a‐5p targets LYPLA1 and regulates global protein palmitoylation level in late‐onset hypogonadism males
Authors: Qu Mengyuan , Zhao Yunhan , Qing Xingrong , Zhang Xinzong , Li Honggang 
Published: December 2020

AbstractLate‐onset hypogonadism (LOH) is defined as a clinical and biochemical syndrome with multiple symptoms caused by testosterone deficiency in aging males. An in‐depth exploration of the molecular mechanism underlying LOH development is insufficient. We previously identified miR‐125a‐5p as a dysregulated microRNA in LOH patients and potential diagnostic biomarker for LOH. The present study demonstrated that plasma miR‐125a‐5p was upregulated after testosterone supplementation in both LOH patients and castrated mice, and positively associated with the testosterone concentrations, suggesting direct regulation of miR‐125a‐5p expression by testosterone. Androgen response element in the promoter of miR‐125a‐5p was subsequently identified. Target gene screening and confirmation verified that LYPLA1, encoding acyl‐protein thioesterase 1 which catalyzed protein depalmitoylation process, was a target gene of miR‐125a‐5p. Furthermore, in cells cultured with testosterone deprivation and organs from castrated mice, testosterone deficiency led to decreased global protein palmitoylation level. In aging males, global protein palmitoylation in peripheral blood showed a notable decline in LOH patients contrast to the normal elderly males. And the palmitoylation level was positively correlative with serum testosterone concentrations. Our results suggested that testosterone could regulate global palmitoylation level through miR‐125a‐5p/LYPLA1 signaling pathway. Given that protein palmitoylation is pivotal for protein function and constitutes the pathogenesis of various diseases, testosterone/miR‐125a‐5p/LYPLA1 may contribute to the molecular mechanism underlying multiple symptoms caused by testosterone deficiency in LOH patients, and aberrant global palmitoylation could be a potential biomarker for LOH.
Association between serum albumin and cognitive dysfunction in hepatic encephalopathy: An exploratory data analysis
Authors: Kaji Kosuke , Okita Kiwamu , Suzuki Kazuyuki , Sato Ikuya , Fujisawa Masaki , Yoshiji Hitoshi 
Published: December 2020

AbstractBackground and AimBecause covert hepatic encephalopathy (CHE) has been shown to affect the prognosis of cirrhotic patients, early diagnosis of hepatic encephalopathy (HE) is a prerequisite for the preservation of patients' quality of life and for prophylaxis of overt HE. The aim of this study was to identify a clinical parameter to predict impairment of cognitive function in cirrhotic patients with early‐stage HE.MethodsWe investigated the data from 172 patients with cirrhotic or idiopathic portosystemic shunt (PSS) in phase II/III trials of rifaximin in Japan. Classification and regression trees (CARTs) were constructed to identify clinical profiles related to cognitive dysfunction as indicated by the prolongation of time required for the Number Connection Test (NCT‐B).ResultsCART analysis detected age 65 years as the variable for the initial split, and serum albumin level was selected as the variable for the second split among patients aged ≤65 years. In 27 cirrhotic patients aged ≤65 years without PSS, receiver operating characteristic curve analysis revealed that the optimal albumin level cutoff point was 3.05 g/dL, and the area under the curve was 0.80 for the prolongation of NCT‐B time, which was higher than that of the branched‐chain amino acids‐to‐tyrosine ratio (0.46), the prothrombin time–international normalized ratio (PT‐INR) (0.68), serum ammonia (0.61), and total bilirubin (0.69).ConclusionsLower serum albumin level as a clinical biomarker associated with impaired cognitive function may be available as a screening examination for early‐stage HE in cirrhotic patients aged ≤65 years without PSS before undergoing neuropsychological tests.
Mental health, substance use and viral suppression in adolescents receiving ART at a paediatric HIV clinic in South Africa
Authors: Haas Andreas D , Technau Karl‐Günter , Pahad Shenaaz , Braithwaite Kate , Madzivhandila Mampho , Sorour Gillian , Sawry Shobna , Maxwell Nicola , von Groote Per , Tlali Mpho , Davies Mary‐Ann , Egger Matthias ,   for the IeDEA Southern Africa Collaboration
Published: December 2020

AbstractIntroductionMental health problems are prevalent in adolescents living with HIV (ALHIV), often remain untreated, and may negatively affect antiretroviral therapy (ART) adherence and viral suppression. We implemented routine mental health screening at a paediatric ART clinic to improve the identification and management of mental health problems in ALHIV. In this report, we examine screening outcomes, associated patient characteristics and the odds of unsuppressed viral load in ALHIV screening positive for mental disorders.MethodsAdolescents aged 10 to 19 years attending Rahima Moosa Hospital in Johannesburg, South Africa between February 1, 2018, and January 1, 2020, were offered mental health screening at each routine HIV care visit. The screening included four pre‐screening questions followed by full screening (conditional on positive pre‐screening) for depression (Patient Health Questionnaire‐9 [PHQ‐9]), suicide (Adolescent Innovations Project [AIP]‐handbook), anxiety (Generalized Anxiety Disorder‐7 [GAD‐7]), post‐traumatic stress disorder (PTSD) (Primary Care PTSD Screen [PC‐PTSD‐5]) and substance use (CAGE Adapted to Include Drugs [CAGE‐AID]). We assessed screening outcomes and calculated adjusted odds ratios for associations between positive screening tests at the first screen and unsuppressed viral load (>400 copies/mL) at the measurement taken closest to the date of screening, within hundred days before and one day after screening.ResultsOut of 1203 adolescents who attended the clinic, 1088 (90.4%) were pre‐screened of whom 381 (35.0%) underwent full screening, 48 (4.4%) screened positive for depression (PHQ‐9 ≥10), 29 (2.8%) for suicidal concern, 24 (2.2%) for anxiety (GAD‐7 ≥10), 38 (3.2%) for PTSD (PC‐PTSD‐5 ≥3), 18 (1.7%) for substance use (CAGE‐AID ≥2) and 97 (8.9%) for any of these conditions. Positive screening for depression (aOR 2.39, 95% CI 1.02 to 5.62), PTSD (aOR 3.18, 95% CI 1.11 to 9.07), substance use (aOR 7.13, 95% CI 1.60 to 31.86), or any condition (aOR 2.17, 95% CI 1.17 to 4.02) were strongly associated with unsuppressed viral load.ConclusionsALHIV affected by mental health problems have increased rates of unsuppressed viral load and need specific clinical attention. The integration of routine mental health screening in paediatric ART programmes is a feasible approach for identifying and referring adolescents with mental health and adherence problems to counselling and psychosocial support services and if needed to psychiatric care.
Pathways for reduction of HIV‐related stigma: a model derived from longitudinal qualitative research in Kenya and Uganda
Authors: Camlin Carol S , Charlebois Edwin D , Getahun Monica , Akatukwasa Cecilia , Atwine Frederick , Itiakorit Harriet , Bakanoma Robert , Maeri Irene , Owino Lawrence , Onyango Anjeline , Chamie Gabriel , Clark Tamara D , Cohen Craig R , Kwarisiima Dalsone , Kabami Jane , Sang Norton , Kamya Moses R , Bukusi Elizabeth A , Petersen Maya L , V Havlir Diane 
Published: December 2020

AbstractIntroductionThe rollout of antiretroviral therapy (ART) has been associated with reductions in HIV‐related stigma, but pathways through which this reduction occurs are poorly understood. In the newer context of universal test and treat (UTT) interventions, where rapid diffusion of ART uptake takes place, there is an opportunity to understand the processes through which HIV‐related stigma can decline, and how UTT strategies may precipitate more rapid and widespread changes in stigma. This qualitative study sought to evaluate how a UTT intervention influenced changes in beliefs, attitudes and behaviours related to HIV.MethodsLongitudinal qualitative in‐depth semi‐structured interview data were collected within a community‐cluster randomized UTT trial, the Sustainable East Africa Research in Community Health (SEARCH) study, annually over three rounds (2014 to 2016) from two cohorts of adults (n = 32 community leaders, and n = 112 community members) in eight rural communities in Uganda and Kenya. Data were inductively analysed to develop new theory for understanding the pathways of stigma decline.ResultsWe present an emergent theoretical model of pathways through which HIV‐related stigma may decline: internalized stigma may be reduced by two processes accelerated through the uptake and successful usage of ART: first, a reduced fear of dying and increased optimism for prolonged and healthy years of life; second, a restoration of perceived social value and fulfilment of subjective role expectations via restored physical strength and productivity. Anticipated stigma may be reduced in response to widespread engagement in HIV testing, leading to an increasing number of HIV status disclosures in a community, “normalizing” disclosure and reducing fears. Improvements in the perceived quality of HIV care lead to people living with HIV (PLHIV) seeking care in nearby facilities, seeing other known community members living with HIV, reducing isolation and facilitating opportunities for social support and “solidarity.” Finally, enacted stigma may be reduced in response to the community viewing the healthy bodies of PLHIV successfully engaged in treatment, which lessens the fears that trigger enacted stigma; it becomes no longer socially normative to stigmatize PLHIV. This process may be reinforced through public health messaging and anti‐discrimination laws.ConclusionsDeclines in HIV‐related stigma appear to underway and explained by social processes accelerated by UTT efforts. Widespread implementation of UTT shows promise for reducing multiple dimensions of stigma, which is critical for improving health outcomes among PLHIV.
Tissue‐level cytokines in a rodent model of chronic implant‐associated infection
Authors: Prince Nicole , Penatzer Julia A. , Shackleford Taylor L. , Stewart Elizabeth K. , Dietz Matthew J. , Boyd Jonathan W. 
Published: December 2020

AbstractSystemic cytokine concentrations have been extensively studied in implant‐associated infections, providing sensitive diagnostic markers. However, less is known about the relationships of tissue‐level cytokines surrounding the joint. The aim of this study was to define the cytokine profiles of tissues to investigate the use of these cytokines as markers of debridement in chronic joint infection. Using a rodent model, muscle samples were obtained from rats following Kirschner wire implantation and infection with Staphylococcus aureus to determine if: (1) differences exist in cytokine concentrations with proximity to infection, and (2) localized infection‐specific markers can be identified on a tissue level to potentially serve as debridement markers in the future. Samples were collected from 4 distinct locations, and the concentrations of interleukin(IL)‐1α, IL‐1β, IL‐4, IL‐5, IL‐6, IL‐10, IL‐12p70, IL‐13, granulocyte‐macrophage colony‐stimulating factor, interferon‐γ, and tumor necrosis factor‐α were quantified in each sample, relative to the amount of tissue. Cytokine concentrations differed with proximity to the joint when implant or infection was present, and tissues at the operative knee joint showed the highest levels of most cytokines. Additionally, IL‐1β, IL‐4, and IL‐6 showed promise, beyond diagnostics, as tissue‐level indicators of infection response. Ultimately, this study illustrated that tissue‐level evaluation provided insight into infection‐specific response, and these markers may be useful for guiding the debridement of implant‐associated infections.
Reduction of Shear Wave Elastography but Not Shear Wave Dispersion After Successful Hepatitis C Treatment With Direct‐Acting Antiviral Agents
Authors: Su Pei‐yuan , Su Wei‐Wen , Wu Li‐sha , Hsu Po‐Ke , Huang Siou‐Ping , Hsu Yu‐Chun 
Published: December 2020

ObjectivesSuccessful antiviral treatment in patients with hepatitis C can lead to reduced liver stiffness. In this study, we attempted to compare 2‐dimensional (2D) shear wave elastography (SWE), shear wave dispersion (SWD), and attenuation imaging (ATI) with transient elastography (TE) and the controlled attenuation parameter (CAP) in patients under direct‐acting antiviral (DAA) therapy.MethodsPatients with chronic hepatitis C infection undergoing DAA therapy from January 2017 to June 2020 were retrospectively examined. The results of 2D SWE, SWD, ATI, TE, and CAP were recorded before and 12 weeks after the completion of DAA therapy.ResultsA total of 122 patients with a median age of 61 years were investigated; among them, 121 (99.2%) achieved a sustained virologic response at 12 weeks after DAA therapy. Fibrosis 4, the aspartate aminotransferase–to–platelet ratio index, 2D SWE, and TE were reduced after DAA therapy. The CAP was increased; however, SWD and ATI showed no statistically significant changes after DAA therapy. Two‐dimensional SWE and TE were strongly correlated (r = 0.885–0.897; P < .001). Albumin and the baseline liver stiffness measurement were independent factors of liver stiffness measurement changes after DAA therapy.ConclusionsDirect‐acting antiviral therapy can significantly decrease liver stiffness (using both 2D SWE and TE) but not SWD and ATI values in patients with hepatitis C. An increased CAP is also observed after DAA therapy.
Dissolved organic carbon (DOC) is essential to balance the metabolic demands of four dominant North‐Atlantic deep‐sea sponges
Authors: Bart Martijn C. , Mueller Benjamin , Rombouts Titus , van de Ven Clea , Tompkins Gabrielle J. , Osinga Ronald , Brussaard Corina P.D. , MacDonald Barry , Engel Anja , Rapp Hans Tore , de Goeij Jasper M. 
Published: December 2020

AbstractSponges are ubiquitous components of various deep‐sea habitats, including cold water coral reefs, and form deep‐sea sponge grounds. Although the deep sea is generally considered to be a food‐limited environment, these ecosystems are known to be hotspots of biodiversity and carbon cycling. To assess the role of sponges in the carbon cycling of deep‐sea ecosystems, we studied the carbon budgets of six dominant deep‐sea sponges of different phylogenetic origin, with various growth forms and hosting distinct associated microbial communities, in an ex situ aquarium setup. Additionally, we determined biomass metrics—planar surface area, volume, wet weight, dry weight (DW), ash‐free dry weight, and organic carbon (C) content—and conversion factors for all species. Oxygen (O2) removal rates averaged 3.3 ± 2.8 μmol O2 g DWsponge h−1 (mean ± SD), live particulate (bacterio‐ and phytoplankton) organic carbon removal rates averaged 0.30 ± 0.39 μmol C g DWsponge h−1 and dissolved organic carbon (DOC) removal rates averaged 18.70 ± 25.02 μmol C g DWsponge h−1. Carbon mass balances were calculated for four species and revealed that the sponges acquired 1.3–6.6 times the amount of carbon needed to sustain their minimal respiratory demands. These results indicate that irrespective of taxonomic class, growth form, and abundance of microbial symbionts, DOC is responsible for over 90% of the total net organic carbon removal of deep‐sea sponges and allows them to sustain themselves in otherwise food‐limited environments on the ocean floor.
Rational Design of Ratiometric Luminescence Thermometry Based on Thermally Coupled Levels for Bioapplications
Authors: Suo Hao , Zhao Xiaoqi , Zhang Zhiyu , Wang Yu , Sun Jiashu , Jin Minkun , Guo Chongfeng 
Published: December 2020

AbstractNoninvasive lanthanide‐doped optical thermometers based on fluorescent intensity ratio (FIR) technique have emerged as promising noncontact tools for detecting the inaccessible objects at different scales. Currently, the theoretical and experimental investigations of various influential factors on thermal performances of luminescence thermometers have become one of the hotspots to develop highly sensitive optical thermometers. On the other hand, near‐infrared (NIR) light‐responsive nanothermometers with deep‐tissue penetration have been widely applied for subcutaneous and intracellular thermometry, which could be integrated with optical heating and imaging functions to construct all‐in‐one thermometer‐heater platforms for cancer diagnosis and therapy. In this review, the recent advances in luminescence thermometry based on the thermally coupled levels (TCLs) are elaborately introduced from fundamental aspects to possible biomedical applications, with the perspective and outlook in the emerging challenges of FIR thermometers applied in biomedical science.
Triggering Forces at the Nanoscale: Technologies for Single‐Chain Mechanical Activation and Manipulation
Authors: Martínez‐Tong Daniel E. , Pomposo José A. , Verde‐Sesto Ester 
Published: December 2020

AbstractOver the past decades, polymer mechanochemistry has focused on the development and application of advanced force application methods to better understand the mechanochemical response of mechanophores. In this regard, techniques such as ultrasonication and single‐molecule force spectroscopy (SMFS) are used to activate and detect up to thousands of chemical events within a polymer single chain, allowing the researchers to probe the mechanochemical reactivity of these stress‐responsive motifs. Here, the most recent contributions of the single‐molecule force spectroscopy technique to this field are presented, putting emphasis on the fundamental parameters of the technique for triggering specific force responses and on the description of force–extension curves measured for single‐ and multi‐mechanophore polymers. Moreover, new contributions of microscopy‐based techniques in the field of polymer mechanochemistry, as well as the potential application of single‐chain nanoparticles as mechanoresponsive materials, are highlighted.
Toll‐like receptor‐4 deficiency inhibits ultraviolet radiation‐induced tumor development by modulation of immune and inflammatory responses
Authors: Ahmad Israr , Nasti Tahseen H. , Rihan Heba M. , Jimenez Hugo , Elmets Craig A. , Yusuf Nabiha 
Published: December 2020

AbstractUltraviolet (UV) B irradiation of the skin induces acute inflammation, as characterized by erythema, edema, and immunosuppression, and is subsequently linked to the progression of skin cancer. Toll‐like receptor 4 (TLR4), a component of innate immunity, has been shown to play an important role in cancer. To elucidate the role of TLR4 in UVB‐induced tumor development, TLR4‐proficient (C3H/HeN) and TLR4‐deficient (C3H/HeJ) mice were exposed to multiple doses of UVB radiation (200 mJ/cm2) for 40 weeks. Photocarcinogenesis was retarded in terms of tumor incidence, and tumor latency, in mice deficient in TLR4 compared with TLR4‐proficient mice, whereas significantly greater numbers of tumors occurred in TLR4‐proficient mice. There was significant upregulation of inflammatory markers like COX‐2, PGE2, S100A8, and S100A9 in the skin of TLR4‐proficient mice than the skin of TLR4‐deficient mice. Furthermore, we found that TLR4‐proficient mice had a significantly higher number of Gr1+CD11b+ myeloid cells CD4+CD25+ regulatory T‐cells than TLR4‐deficient mice. Furthermore, the levels of interferon (IFN)‐γ cytokine was increased and the levels of interleukin (IL)‐4, IL‐10, and IL‐17 cytokines were decreased in serum, skin, and tumor lysates of TLR4‐deficient mice in comparison with samples from TLR4‐proficient mice. Together, our data indicate that TLR4‐mediated inflammation may cause suppression of antitumor responses and trigger the development of UVB‐induced skin cancers. Thus, strategies to inhibit TLR4‐mediated immune suppression may allow us to develop preventive and therapeutic approaches for the management of UVB‐induced cutaneous tumors.
Plasma Phospho‐Tau Identifies Alzheimer's Co‐Pathology in Patients with Lewy Body Disease
Authors: Hall Sara , Janelidze Shorena , Londos Elisabet , Leuzy Antoine , Stomrud Erik , Dage Jeffrey L. , Hansson Oskar 
Published: December 2020

ABSTRACTBackgroundAlzheimer's disease co‐pathology is common in dementia with Lewy bodies and Parkinson's disease with dementia (Lewy body disease) and can reliably be detected with positron emission tomography (PET) or cerebrospinal fluid (CSF) biomarkers. Recently developed blood biomarkers are more accessible and less expensive alternatives.ObjectiveTo investigate if plasma phospho‐tau217 and phospho‐tau181 can detect Alzheimer's pathology in Lewy body disease with dementia.MethodsIn this cross‐sectional study we investigated plasma phospho‐tau217 and phospho‐tau181 in 35 patients with Lewy body disease with dementia. Patients underwent tau‐PET imaging (18F‐RO948).ResultsPlasma phospho‐tau217 correlated with plasma phospho‐tau181, CSF phospho‐tau217 (rs = 0.68, P < 0.001), and negatively with CSF β‐amyloid42/40 (rs = −0.52, P = 0.001). Plasma phospho‐tau217 and phospho‐tau181 correlated with tau‐PET signal in the temporal cortex (rs > 0.56, P < 0.001) and predicted abnormal tau‐PET status and β‐amyloid status (area under the curve > 0.78 and > 0.81, respectively).ConclusionPlasma phospho‐tau might be a useful marker for Alzheimer's co‐pathology in Lewy body disease with dementia. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Milk Fat Globule Membrane as a Modulator of Infant Metabolism and Gut Microbiota: A Formula Supplement Narrowing the Metabolic Differences between Breastfed and Formula‐Fed Infants
Authors: Lee Hanna , Slupsky Carolyn M. , Heckmann Anne B. , Christensen Britt , Peng Yongmei , Li Xiaonan , Hernell Olle , Lönnerdal Bo , Li Zailing 
Published: December 2020

ScopeMilk fat globule membrane (MFGM) is an important component of milk that has previously been removed in the manufacture of infant formulas, but has recently gained attention owing to its potential to improve immunological, cognitive, and metabolic health. The goal of this study is to determine whether supplementing MFGM in infant formula would drive desirable changes in metabolism and gut microbiota to elicit benefits observed in prior studies.Methods and ResultsThe serum metabolome and fecal microbiota are analyzed using 1H NMR spectroscopy and 16S rRNA gene sequencing respectively in a cohort of Chinese infants given a standard formula or a formula supplemented with an MFGM‐enriched whey protein fraction. Supplementing MFGM suppressed protein degradation pathways and the levels of insulinogenic amino acids that are typically enhanced in formula‐fed infants while facilitating fatty acid oxidation and ketogenesis, a feature that may favor brain development. MFGM supplementation did not induce significant compositional changes in the fecal microbiota but suppressed microbial diversity and altered microbiota‐associated metabolites.ConclusionSupplementing MFGM in a formula reduced some metabolic gaps between formula‐fed and breastfed infants.