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Moreover, our findings link α-Syn- enhanced axonal growth with evidence for axonal injury. In relevance to disease mechanisms, we detect in human brains evidence for a higher degree of corticostriatal glutamatergic plasticity within WMTs at early stages of PD. However, at later PD stages, the respective WMTs in the caudate are degenerated with accumulation of Lewy pathology. CONCLUSIONS Our results show that through regulating PI4,5P2 levels, α-Syn acts to elongate the main axon and collaterals, resulting in a higher density of axons in the striatal WMTs. Based on these results we suggest a role for α-Syn in compensating mechanisms, involving corticostriatal glutamatergic plasticity, taking place early in PD.The human epigenome has been experimentally characterized by thousands of measurements for every basepair in the human genome. We propose a deep neural network tensor factorization method, Avocado, that compresses this epigenomic data into a dense, information-rich representation. We use this learned representation to impute epigenomic data more accurately than previous methods, and we show that machine learning models that exploit this representation outperform those trained directly on epigenomic data on a variety of genomics tasks. These tasks include predicting gene expression, promoter-enhancer interactions, replication timing, and an element of 3D chromatin architecture.BACKGROUND Tumor repopulation is a major cause of radiotherapy failure. Previous investigations highlighted that dying tumor cells played vital roles in tumor repopulation through promoting proliferation of the residual tumor repopulating cells (TRCs). However, TRCs also suffer DNA damage after radiotherapy, and might undergo mitotic catastrophe under the stimulation of proliferative factors released by dying cells. Hence, we intend to find out how these paradoxical biological processes coordinated to potentiate tumor repopulation after radiotherapy. METHODS Tumor repopulation models in vitro and in vivo were used for evaluating the therapy response and dissecting underlying mechanisms. RNA-seq was performed to find out the signaling changes and identify the significantly changed miRNAs. qPCR, western blot, IHC, FACS, colony formation assay, etc. were carried out to analyze the molecules and cells. RESULTS Exosomes derived from dying tumor cells induced G1/S arrest and promoted DNA damage response to potentiate survival of TRCs through delivering miR-194-5p, which further modulated E2F3 expression. Moreover, exosomal miR-194-5p alleviated the harmful effects of oncogenic HMGA2 under radiotherapy. After a latent time, dying tumor cells further released a large amount of PGE2 to boost proliferation of the recovered TRCs, and orchestrated the repopulation cascades. Of note, low-dose aspirin was found to suppress pancreatic cancer repopulation upon radiation via inhibiting secretion of exosomes and PGE2. CONCLUSION Exosomal miR-194-5p enhanced DNA damage response in TRCs to potentiate tumor repopulation. Combined use of aspirin and radiotherapy might benefit pancreatic cancer patients.BACKGROUND Inflammatory response is activated during cardiopulmonary bypass (CPB), which may lead to acute respiratory distress syndrome (ARDS) and procalcitonin (PCT) increases during this inflammatory response. The objective of the study was to validate whether patients with higher serum PCT concentrations have a higher incidence of ARDS. METHODS The study was a prospective, single-center, observational cohort study. All patients who received cardiac surgery with CPB were screened for study eligibility. Patients were assigned to the PCT-elevated cohort or the control cohort according to serum PCT concentration on the first postoperative day with a cut-off value of 7.0 ng/mL. Patients were followed up until the 7th postoperative day. The primary endpoint was the incidence of ARDS, which was diagnosed according to the Berlin definition. RESULTS A total of 296 patients were enrolled, 64 patients were assigned to the PCT-elevated cohort and 232 patients were assigned to the control cohort. PCT concentration was may serve as a warning signal of postoperative ARDS in patients undergoing cardiac surgery with CPB. Study registration Chinese Clinical Trial Registry (ChiCTR-OCH-14005076).BACKGROUND The species-specific mode of action for DEET and many other mosquito repellents is often unclear. Confusion may arise for many reasons. First, the response of a single mosquito species is often used to represent all mosquito species. Second, behavioural studies usually test the effect of repellents on mosquito attraction towards human odorants, rather than their direct repulsive effect on mosquitoes. Third, the mosquito sensory neuron responses towards repellents are often not directly examined. METHODS A close proximity response assay was used to test the direct repulsive effect of six mosquito repellents on Anopheles coluzzii, Aedes aegypti and Culex quinquefasciatus mosquitoes. Additionally, the behavioural assay and calcium imaging recordings of antennae were used to test the response of An. coluzzii mosquitoes towards two human odorants (1-octen-3-ol and benzaldehyde) at different concentrations, and mixtures of the repellents lemongrass oil and p-menthane-3,8-diol (PMD) with DEET. RESULTS Anoive repellent blends, and could ultimately identify the olfactory neurons and receptors in mosquitoes that mediate repellency.AIM Evidence is emerging that prescription opioid (PO) injection is associated with increased health risks. This mixed-methods study compares the mechanics of PO and heroin injection and examines the demographic and drug-related correlates of lifetime PO injection in a sample of young people who inject drugs (PWID) in New York City (NYC). METHODS Qualitative analysis of 46 semi-structured interviews with young adult opioid users ages 18-32. find more Interview segments describing PO injection were analyzed for common themes. Quantitative analysis of structured interviews with 539 young adult opioid users ages 18-29 recruited via respondent-driven sampling (RDS). Analyses are based on the subsample of 353 participants (65%) who reported having ever injected drugs. All variables were assessed via self-report, except hepatitis C virus status, which was established via rapid antibody testing. RESULTS Participants described injecting POs and reported that preparing abuse-deterrent pills for injection is especially cumbersomcrease risk for blood-borne viral infection (e.g., repeated injections) and predicted testing HCV-positive, as well as overdose. PO injection may also serve as a marker for a subgroup of PWID at elevated risk for multiple drug use-related comorbidities. Programs that provide prevention services to PWID need to tailor harm reduction measures and messaging to the specific practices and harms associated with the injection of POs.BACKGROUND Several refugee settlements in Bangladesh have provided housing and medical care for the forcibly-displaced Myanmar nationals (FDMN, also known as Rohingya) population. The identification of malaria infection status in the refugee settlements is useful in treating infected persons and in developing malaria prevention recommendations. Assays for Plasmodium antigens and human IgG against Plasmodium parasites can be used as indicators to determine malaria infection status and exposure. METHODS Dried blood spot (DBS) samples (N = 1239) from a household survey performed April-May 2018 in three settlements in Cox's Bazar district, Bangladesh were utilized for a sample population of children from ages 1-14 years of age. The samples were tested using a bead-based multiplex antigen assay for presence of the pan-Plasmodium antigen aldolase as well as Plasmodium falciparum histidine rich protein 2 (HRP2). A bead-based multiplex assay was also used to measure human IgG antibody response to P. falciparum, Plasmduring the malaria high-transmission season indicate these migrant populations were likely at increased risk of malaria exposure during their transit.OBJECTIVES Iguratimod, a novel immunomodulatory agent for rheumatoid arthritis, has been shown to be effective against murine lupus. The aim of this study was to make a preliminary evaluation of the efficacy and safety of iguratimod as salvage therapy in patients with refractory lupus nephritis (LN). METHODS We enrolled eligible patients with refractory LN, which we defined as having failed or relapsed on at least two immunosuppressant agents. After enrollment, we substituted iguratimod (25 mg twice daily) for their previous immunosuppressant agents without increasing the dose of steroids. The primary outcome was complete/partial remission (PR/CR) at week 24. Patients who achieved remission continued iguratimod as maintenance therapy over an extended follow-up. RESULTS The study cohort comprised 14 patients with refractory LN, 10 of whom had recent treatment failure and 4 repeated relapses with inadequate initial responses. At enrollment, none of the patients had detectable evidence of extra-renal involvement. The median prednisone dosage was 10 mg/d (IQR 0-10 mg/day). Thirteen patients were eligible for response evaluation, with one patient missed. The renal response rate was 92.3% (12/13) at week 24, with 38.5% (5/13) achieving CR and 53.8% (7/13) achieving PR. We then continued to follow up the responding patients for up to 144 weeks. Twenty-five percent of the patients (3/12) had renal relapse after initial PR. The estimated glomerular filtration rate of all patients maintained stable during follow-up. One patient had a severe adverse reaction (anemia) but recovered fully after stopping iguratimod. CONCLUSIONS Our study supports the potential of iguratimod for treatment of refractory LN. Iguratimod could be a promising candidate drug for this condition.BACKGROUND One of the main objectives of health policy-makers is to promote children's growth, development, and survival. The current research evaluates the impact of breastfeeding on infant survival and highlights the major socio-economic determinants of child survival from 0 to 5 years old in Côte d'Ivoire. METHODS This study uses Probit estimation to evaluate the impact of the type of breastfeeding on the survival of children aged from 0 to 5 years old. The main socio-economic determinants of child survival were identified and analyzed. The sample of the study covers 7776 children under 5 years old drawn from the Côte d'Ivoire Demographic Health Surveys and the Multiple Indicators cluster survey of 2012. RESULTS A child is more likely to survive when immediate exclusive breastfeeding was practiced for up to 6 months. The probability of survival increases significantly when the mother lives in a healthy environment, when she has at least a primary school education, and when she plays a leading role in carin order to promote the welfare and health of their children.BACKGROUND Hypoxemia is a severe condition associated with high rates of mortality, particularly in low- and middle-income countries (LMICs) with poor access to oxygen therapy. Despite its clinical significance, there have been few studies to describe the burden of hypoxemia. Thus, the primary objective of this study is to systematically describe the prevalence of hypoxemia among pediatric and adult patients in low- and middle-income countries. METHODS/DESIGN Standard systematic review methods will be used. Bibliographic databases (MEDLINE, EMBASE, CINAHL) will be searched from 1998 onwards. The search strategy aims to identify studies that have measured peripheral blood oxygen saturation (SpO2) in children and adults presenting to health facilities in LMICs. Studies will be included if oxygen saturation measurements by pulse oximetry were measured. No studies will be excluded based on study design though patients recruited from intensive care units and post-operative care will be excluded. The primary outcome is the prevalence of hypoxemia on presentation to the healthcare facility.
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