bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systematic review and meta-analysis of acupuncture treatment for oral ulcer
Authors: Yan Hang , Jin Zhao , Jin Wenqin , Zhong Yanmei , Ai Huangping , Wu Yeke , Xu Qianrong , Bai Xiaoyan , Liu Donghao , Nie Wenhan , Zuo Yuling 
Published: July 2020

Abstract

Background:
Oral ulcers (OU) is a common oral mucosal disease manifested with obvious pain; in some studies, the efficacy of acupuncture in OU has been confirmed, but the systematic reviews and meta-analyses for them are lacking. Our aim is to evaluate the efficacy and safety of acupuncture in the treatment of OU.

Methods:
Relevant randomized controlled trials (RCTs), quasi RCTs and non-RCTs will be identified by systematic searching from the following electronic databases: PubMed, Embase, the Cochrane Library, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, China Science and Technology Journal database, and Wanfang Data (since inception of the databases to present). In addition, ongoing trials will be retrieved from the Chinese Clinical Trial Register, World Health Organization International Clinical Trials Registry Platform, Clinical Trials, and The Clinical Trials Register. Grey literature will be also taken into consideration, including academic dissertation, minutes of the meeting from Chinese Biomedical Literature Database, China National Knowledge Infrastructure, China Science and Technology Journal database, and Wanfang Data. There are no language restrictions.

Results:
Ethical approval is not required because this study is based on published papers. After peer-review, the study will be disseminated in scientific journals and conferences.

Conclusion:
This systematic review will provide evidence for the efficacy and safety of acupuncture for Oral ulcers.

Trial registration number:
CRD42020144911.
Chemotherapy efficacy after first-line immunotherapy in 18 advanced melanoma patients
Authors: Saint-Jean Mélanie , Fronteau Clémentine , Peuvrel Lucie , Khammari Amir , Varey Emilie , Quéreux Gaëlle , Dréno Brigitte 
Published: July 2020

Abstract
In BRAF wild type advanced melanoma, immune checkpoint blockers such as anti-PD1 (anti-programmed cell death 1) are usually continued beyond progression for a hypothetical rare further response. Chemotherapy as a second-line option is considered ineffective by many practitioners based on historical data. Continuing anti-PD1 beyond progression has a high health-economic impact and is not recommended by the FDA. This study aimed to describe the efficacy and survival of advanced melanoma patients who received second-line (or more) chemotherapy after immunotherapy failure.
This was a retrospective single center study conducted in a French University Hospital during an 11-month period. All advanced melanoma patients treated with chemotherapy after immunotherapy failure were included.
Eighteen patients were analyzed. Therapeutic response to chemotherapy was evaluable in 16 patients: partial response was achieved in 3/16 (19%), stable disease in 1/16 (6%) and progressive disease in 12/16 (75%). Median overall survival from chemotherapy start was 12 months. Median progression-free survival was 5.4 months. The 6-month overall survival rate was 81% and the 6-month progression-free survival rate was 40%.
Although the disease control rate with chemotherapy was low (25%), survival data in our study are far superior to those previously published. This could be linked to a high proportion of patients treated with anti-PD1 just prior to chemotherapy, which may suggest a potential synergy between immunotherapy and chemotherapy.
Risk factors for suicidal ideation among the older people living alone in rural region of China
Authors: Hu Caiyun , Zhao Dongdong , Gong Fengfeng , Zhao Yuanyuan , Li Jie , Sun Yehuan 
Published: July 2020

AbstractIn China, suicide accounts for twenty-six percent of all suicides worldwide; however, researches on the suicidal ideation among older people living alone in the rural region are few. We performed a cross-sectional study to explore the prevalence and influence factors of suicidal ideation, and provide a theoretical basis for suicide prevention among older people living alone in rural region.695 older people living alone in rural region were selected by using stratified cluster sampling. Chi-square for categorical variables,T-test for continuous variables, and path analysis were conducted to statistical analysis.The prevalence of suicidal ideation among the elderly living alone in rural China was 23.6%. Path analyses showed that depression had the most substantial influence on suicidal ideation among the elderly living alone, it was also as a mediator between physical, economic status, social support, anxiety, and suicidal ideation; anxiety and social support had both direct and indirect influence on suicidal ideation; physical status and economic status had indirection impact.The incidence of suicidal ideation among the elderly living alone was high in Dangtu county. Psychological disorders (anxiety and depression) had the strongest impact on suicidal ideation. Strategies and measures targeting these relevant factors (economic status, physical status, and social support) should be taken to reduce the burdens of suicidal ideation among the elderly living alone in China.
Dynamics and future of SARS-CoV-2 in the human host
Authors: Gillman Michael , Crokidakis Nuno 
Published: July 2020

AbstractForecasting trends in COVID-19 infections is vital for the global economy, national governments and physical and mental well-being. Using the per capita number of new cases as a proxy for the abundance of the SARS-CoV-2 virus, and the number of deaths as a measure of virulence, the dynamics of the pandemic and the outcomes emerging from it are examined for three locations (England, Italy and New York State). The data are analysed with a new version of a population dynamics model that combines exponential/logistic growth with time-varying carrying capacity, allowing predictions of persistence or extinction of the virus. In agreement with coevolutionary theory, the model suggests a transition from exponential virus growth to low abundance, coupled with reduced virulence, during colonisation of the alternate human host. The structure of the model allows a straightforward assessment of key parameters, which can be contrasted with standard epidemiological models and interpreted with respect to ecological and evolutionary processes and isolation policies.
The utility of Resting Pulse Rate in Defining High Blood Pressure among Adolescents in Mbarara Municipality, Uganda
Authors: Katamba Godfrey , Agaba David Collins , Namayanja Rosemary , Namaganda Agnes , Musasizi Abdul , Kinene Mivule Abdul , Migisha Richard 
Published: July 2020

AbstractHigh resting pulse rate (RPR) is associated with adverse cardiovascular events, and could be used as a marker of cardiovascular health. We determined the correlation between RPR and blood pressure (BP); and its accuracy in defining high blood pressure among adolescents attending secondary schools in Mbarara municipality, south-western Uganda. We conducted a cross-sectional study among secondary school adolescents aged 12-19 years in Mbarara municipality, Uganda. We captured demographic characteristics using a structured questionnaire; and measured anthropometric indices and BP. We performed a linear regression analysis to determine the relationship between RPR and blood pressure and plotted receiver operating characteristics curves (ROC) to assess the accuracy of RPR in defining high BP. We enrolled 616 adolescents with a mean age of 15.6±2.0 years and 65.6% (404/616) were female. The RPR was significantly correlated with diastolic blood pressure (DBP) in both boys (Beta = 0.22 [95%CI: 0.10; 0.36]), p<0.001 and girls (Beta = 0.51 [95%CI: 0.43; 0.60]), p<0.001. RPR was significantly correlated with systolic blood pressure (SBP) only in the girls (Beta = 0.23 [95%CI: 0.15; 0.30]), p<0.001. The optimal threshold for RPR in defining prehypertension was RPR≥76bpm with an area under the curve (AUC) of 0.653[95%CI: 0.583-0.722], the sensitivity of 0.737 and specificity of 0.577. In defining hypertension, the optimal threshold was RPR ≥ 79bpm at a sensitivity of 0.737 and specificity of 0.719, with an AUC of 0.728[95%CI: 0.624-0.831]. Resting pulse rate was positively correlated with BP and was more accurate in defining hypertension compared to prehypertension in the study.
Methylome-wide analysis reveals epigenetic marks associated with resistance to tuberculosis in HIV-infected individuals from East Africa
Authors: Stein Catherine M. , Benchek Penelope , Bartlett Jacquelaine , Igo Robert P. , Sobota Rafal S. , Chervenak Keith , Mayanja-Kizza Harriet , von Reyn C. Fordham , Lahey Timothy , Bush William S. , Boom W. Henry , Scott William K. , Marsit Carmen , Sirugo Giorgio , Williams Scott M. 
Published: July 2020

ABSTRACTBackgroundTuberculosis (TB) is the most deadly infectious disease globally and highly prevalent in the developing world, especially sub-Saharan Africa. Even though a third of humans are exposed to Myocbacterium tuberculosis (Mtb), most infected immunocompetent individuals do not develop active TB. In contrast, for individuals infected with both TB and the human immunodeficiency virus (HIV), the risk of active disease is 10% or more per year. Previously, we identified in a genome-wide association study a region on chromosome 5 that was associated with resistance to TB. This region included epigenetic marks that could influence gene regulation so we hypothesized that HIV-infected individuals exposed to Mtb, who remain disease free, carry epigenetic changes that strongly protect them from active TB. To test this hypothesis, we conducted a methylome-wide study in HIV-infected, TB-exposed cohorts from Uganda and Tanzania.ResultsIn 221 HIV-infected adults from Uganda and Tanzania, we identified 3 regions of interest that included markers that were differentially methylated between TB cases and LTBI controls, that also included methylation QTLs and associated SNPs: chromosome 1 (RNF220, p=4×10−5), chromosome 2 (between COPS8 and COL6A3 genes, p=2.7×10−5), and chromosome 5 (CEP72, p=1.3×10−5). These methylation results colocalized with associated SNPs, methylation QTLs, and methylation × SNP interaction effects. These markers were in regions with regulatory markers for cells involved in TB immunity and/or lung.ConclusionEpigenetic regulation is a potential biologic factor underlying resistance to TB in immunocompromised individuals that can act in conjunction with genetic variants.
Estimating the size of undetected cases of the SARS-CoV-2 outbreak in Europe: An upper bound estimator
Authors: Rocchetti Irene , Böhning Dankmar , Holling Heinz , Maruotti Antonello 
Published: July 2020

AbstractBackgroundWhile the number of detected SARS-CoV-2 infections are widely available, an understanding of the extent of undetected cases is urgently needed for an effective tackling of the pandemic. The aim of this work is to estimate the true number of SARS-CoV-2 (detected and undetected) infections in several European Countries. The question being asked is: How many cases have actually occurred?MethodsWe propose an upper bound estimator under cumulative data distributions, in an open population, based on a day-wise estimator that allows for heterogeneity. The estimator is data-driven and can be easily computed from the distributions of daily cases and deaths. Uncertainty surrounding the estimates is obtained using bootstrap methods.ResultsWe focus on the ratio of the total estimated cases to the observed cases at April 17th. Differences arise at the Country level, and we get estimates ranging from the 3.93 times of Norway to the 7.94 times of France. Accurate estimates are obtained, as bootstrap-based intervals are rather narrow.ConclusionsMany parametric or semi-parametric models have been developed to estimate the population size from aggregated counts leading to an approximation of the missed population and/or to the estimate of the threshold under which the number of missed people cannot fall (i.e. a lower bound). Here, we provide a methodological contribution introducing an upper bound estimator and provide reliable estimates on the dark number, i.e. how many undetected cases are going around for several European Countries, where the epidemic spreads differently.
NetCoMi: Network Construction and Comparison for Microbiome Data in R
Authors: Peschel Stefanie , Müller Christian L. , von Mutius Erika , Boulesteix Anne-Laure , Depner Martin 
Published: July 2020

AbstractEstimating microbial association networks from high-throughput sequencing data is a common exploratory data analysis approach aiming at understanding the complex interplay of microbial communities in their natural habitat. Statistical network estimation workflows comprise several analysis steps, including methods for zero handling, data normalization, and computing microbial associations. Since microbial interactions are likely to change between conditions, e.g. between healthy individuals and patients, identifying network differences between groups is often an integral secondary analysis step. Thus far, however, no unifying computational tool is available that facilitates the whole analysis workflow of constructing, analyzing, and comparing microbial association networks from high-throughput sequencing data.Here, we introduceNetCoMi(NetworkConstruction and comparison forMicrobiome data), anRpackage that integrates existing methods for each analysis step in a single reproducible computational workflow. The package offers functionality for constructing and analyzing single microbial association networks as well as quantifying network differences. This enables insights into whether single taxa, groups of taxa, or the overall network structure change between groups. NetCoMi also contains functionality for constructingdifferential networks, thus allowing to assess whether single pairs of taxa are differentially associated between two groups. Furthermore, NetCoMi facilitates the construction and analysis of dissimilarity networks of microbiome samples, enabling a high-level graphical summary of the heterogeneity of an entire microbiome sample collection. We illustrate NetCoMi’s wide applicability using data sets from the GABRIELA study to compare microbial associations in settled dust from children’s rooms between samples from two study centers (Ulm and Munich).AvailabilityA script withRcode used for producing the examples shown in this manuscript are provided as Supplementary data. The NetCoMi package, together with a tutorial, is available athttps://github.com/stefpeschel/NetCoMi.
When does geography matter most? Age-specific geographical effects in the patterning of, and relationship between, mental wellbeing and mental illness
Authors: Griffith Gareth J , Jones Kelvyn 
Published: July 2020

AbstractMental illness and mental wellbeing are related but distinct constructs. Despite this, geographical enquiry often references the two as interchangeable indicators of mental health and assumes the relationship between the two is consistent across different geographical scales. Furthermore, the importance of geography in such research is commonly assumed to be static for all age groups, despite the large body of evidence demonstrating contextual effects in age-specific populations. We leverage simultaneous measurement of a mental illness and mental wellbeing metric from Understanding Society, a UK population-based survey, and employ bivariate, cross-classified multilevel modelling to characterise the relationship between geographical context and mental health. Results provide strong evidence for contextual effects for both responses before and after covariate adjustment, with weaker evidence for area-classification and PSU-level contextual effects for the GHQ-12 after covariate adjustment. Results support a two-continua model of mental health at the individual level, but indicates that consensual benefit may be achieved across both dimensions by intervening at household and regional levels. There is also some evidence of a greater contextual effects for mental wellbeing than for mental illness. Results highlight the potential of the household as a target for intervention design for consensual benefit across both constructs. Results highlight the increased importance of geographical context for older respondents across both responses. This research supports an area-based approach to improving both mental illness and mental wellbeing in older populations.
Mitochondria-dependent phase separation of disease-relevant proteins drives pathological features of age-related macular degeneration
Authors: Cunza Nilsa La , Tan Li Xuan , Thamban Thushara , Germer Colin J. , Rathnasamy Gurugirijha , Toops Kimberly A. , Lakkaraju Aparna 
Published: July 2020

AbstractAge-related macular degeneration (AMD) damages the retinal pigment epithelium (RPE), the tissue that safeguards photoreceptor health, leading to irreversible vision loss. Polymorphisms in cholesterol and complement genes are implicated in AMD, yet mechanisms linking risk variants to RPE injury remain unclear. We sought to determine how allelic variants in the apolipoprotein E cholesterol transporter modulate RPE homeostasis and function. Using live-cell imaging, we show that inefficient cholesterol transport by the AMD risk-associated ApoE2 increases RPE ceramide, leading to autophagic defects and complement-mediated mitochondrial damage. Mitochondrial injury drives redox state-sensitive cysteine-mediated phase separation of ApoE2, forming biomolecular condensates that could nucleate drusen. The protective ApoE4 isoform lacks these cysteines and is resistant to phase separation and condensate formation. InAbca4-/-Stargardt macular degeneration mice, mitochondrial dysfunction induces liquid-liquid phase separation of p62/SQSTM1, a multifunctional protein that regulates autophagy. Drugs that decrease RPE cholesterol or ceramide prevent mitochondrial injury and phase separation in vitro and in vivo. In AMD donor RPE, mitochondrial fragmentation correlates with ApoE and p62 condensates. Our studies demonstrate that major AMD genetic and biological risk pathways converge upon RPE mitochondria, and identify mitochondrial stress-mediated protein phase separation as an important pathogenic mechanism and promising therapeutic target in AMD.
Coincidence detection of mitogenic signals via cytosolic pH regulates Cyclin D1 expression
Authors: Koch Lisa Maria , Birkeland Eivind , Battaglioni Stefania , Helle Xiao , Meerang Mayura , Hiltbrunner Stefanie , Ibáñez Alfredo J. , Peter Matthias , Curioni Alessandra , Opitz Isabelle , Dechant Reinhard 
Published: July 2020

AbstractEnhanced cell growth and proliferation are accompanied by profound changes in cellular metabolism. Originally identified as the Warburg effect in cancer, such metabolic changes are also common under physiological conditions and include increased fermentation and elevated cytosolic pH (pHc)1,2. However, how these changes contribute to enhanced cell growth and proliferation is unclear. Here, we demonstrate that elevated pHc specifically orchestrates an E2F-dependent transcriptional program to drive cell proliferation by promoting Cyclin D1 expression. pHc-dependent transcription of Cyclin D1 requires the transcription factors CREB1/ATF1 and ETS1 and the Histone Acetyltransferases p300/CBP. Interestingly, biochemical characterization revealed that the CREB1-p300/CBP interaction acts as a pH-sensor and coincidence detector linking different mitotic signals to Cyclin D1 transcription. We also show that elevated pHc contributes to increased Cyclin D1 expression in Malignant Pleural Mesotheliomas (MPMs) and renders them hypersensitive to pharmacological reduction of pHc. Taken together, these data demonstrate that elevated pHc is a critical cellular signal regulating G1 progression and provide a mechanism linking elevated pHc to oncogenic activation of Cyclin D1 in MPMs and possibly other Cyclin D1-dependent tumors. Thus, an increase of pHc may represent a functionally important, early event in the etiology of cancer amenable to therapeutic intervention.
BiPOLES: a tool for bidirectional dual-color optogenetic control of neurons
Authors: Vierock Johannes , Rodriguez-Rozada Silvia , Pieper Florian , Dieter Alexander , Bergs Amelie , Zeitzschel Nadja , Ahlbeck Joachim , Sauter Kathrin , Gottschalk Alexander , Engel Andreas K. , Hegemann Peter , Wiegert J. Simon 
Published: July 2020

AbstractOptogenetic manipulation of neuronal activity has become an indispensable experimental strategy in neuroscience research. A large repertoire of excitatory and inhibitory tools allows precise activation or inhibition of genetically targetable neuronal populations. However, an optogenetic tool for reliable bidirectional control of neuronal activity allowing both up- and downregulation of the same neurons in a single experiment is still missing. Here we report BiPOLES, an optogenetic tool for potent excitation and inhibition of the same population of neurons with light of two different colors. BiPOLES consists of an inhibitory, blue-light-sensitive anion-conducting channelrhodopsin fused to an excitatory, red-light-sensitive cation-conducting channelrhodopsin in a single, trafficking-optimized tandem protein. BiPOLES enables multiple new applications including potent dual-color spiking and silencing of the same neuronsin vivoand dual-color optogenetic control of two independent neuronal populations.
Liver inflammation before spinal cord injury worsens neuropathology, hepatic injury, metabolic syndrome and locomotor deficits
Authors: Goodus Matthew T. , Carson Kaitlin E. , Sauerbeck Andrew D. , Dey Priyankar , Alfredo Anthony N. , Popovich Phillip G. , Bruno Richard S. , McTigue Dana M. 
Published: July 2020

ABSTRACTLiver inflammation can enhance acute leukocyte recruitment to sites of central nervous system (CNS) injury. The consequences of hepatic inflammation on recovery after injury, however, are unknown. Here, we hypothesize that liver inflammation at the time of spinal cord injury (SCI) will exacerbate spinal cord pathology and impair recovery. Rats receiving SCI with concomitant liver inflammation had worse intraspinal pathology and greater locomotor deficits than rats with baseline liver inflammation. Hepatic inflammation also potentiated SCI-induced non-alcoholic steatohepatitis (NASH), endotoxemia, insulin resistance and adiposity. Circulating and cerebrospinal levels of Fetuin-A were higher in SCI rats with liver inflammation. When microinjected into intact spinal cords, Fetuin-A caused robust macrophage activation, iron accumulation and neuron loss. These studies verify that outcomes from CNS injury are worse if the liver is concomitantly inflamed and implicate Fetuin-A as a potential neuropathological mediator. These novel data suggest hepatic inflammation is a potential clinical target for improving recovery from SCI.