bluuebunny/crossref_metadata_2025_split huggingface dataset:
High cases of submicroscopic Plasmodium falciparum infections in a suburban population of Lagos, Nigeria
Authors: Umunnakwe Florence A. , Idowu Emmanuel T. , Ajibaye Olusola , Etoketim Blessed , Akindele Samuel , Shokunbi Aminat O. , Otubanjo Olubunmi A. , Awandare Gordon A. , Amambua-Ngwa Alfred , Oyebola Kolapo M. 
Published: December 2019

Abstract
Background
Asymptomatic malaria parasites are significant sources of infections for onward malaria transmission. Conventional tools for malaria diagnosis such as microscopy and rapid diagnostic test kits (RDT) have relatively low sensitivity, hence the need for alternative tools for active screening of such low-density infections.

Methods
This study tested var acidic terminal sequence-based (varATS) quantitative polymerase chain reaction (qPCR) for screening asymptomatic Plasmodium falciparum infections among dwellers of a sub-urban community in Lagos, Nigeria. Clinically healthy participants were screened for malaria using microscopy, RDT and varATS qPCR techniques. Participants were stratified into three age groups: 1–5, 6–14 and > 14 years old.

Results
Of the 316 participants screened for asymptomatic malaria infection, 78 (24.68%) were positive by microscopy, 99 (31.33%) were positive by RDT and 112 (35.44%) by varATS qPCR. Participants aged 6–14 years had the highest prevalence of asymptomatic malaria, with geometric means of ~ 116 parasites/µL and ~ 6689 parasites/µL as detected by microscopy and varATS, respectively.

Conclusion
This study has revealed high prevalence of asymptomatic malaria in the study population, with varATS detecting additional sub-microscopic infections. The highest concentration of asymptomatic malaria was observed among school-age children between 6 and 14 years old. A large-scale screening to identify other potential hotspots of asymptomatic parasites in the country is recommended.
KIAA1429 contributes to liver cancer progression through N6-methyladenosine-dependent post-transcriptional modification of GATA3
Authors: Lan Tian , Li Hui , Zhang Delin , Xu Lin , Liu Hailing , Hao Xiangyong , Yan Xiaokai , Liao Haotian , Chen Xiangzheng , Xie Kunlin , Li Jiaxin , Liao Mingheng , Huang Jiwei , Yuan Kefei , Zeng Yong , Wu Hong 
Published: December 2019

AbstractBackgroundN6-methyladenosine (m6A) modification, the most abundant internal methylation of eukaryotic RNA transcripts, is critically implicated in RNA processing. As the largest known component in the m6A methyltransferase complex, KIAA1429 plays a vital role in m6A methylation. However, its function and mechanism in hepatocellular carcinoma (HCC) remain poorly defined.MethodsQuantitative PCR, western blot and immunohistochemistry were used to measure the expression of KIAA1429 in HCC. The effects of KIAA1429 on the malignant phenotypes of hepatoma cells were examined in vitroandin vivo. MeRIP-seq, RIP-seq and RNA-seq were performed to identify the target genes of KIAA1429.ResultsKIAA1429 was considerably upregulated in HCC tissues. High expression of KIAA1429 was associated with poor prognosis among HCC patients. Silencing KIAA1429 suppressed cell proliferation and metastasis in vitro and in vivo. GATA3 was identified as the direct downstream target of KIAA1429-mediated m6A modification. KIAA1429 induced m6A methylation on the 3′ UTR of GATA3 pre-mRNA, leading to the separation of the RNA-binding protein HuR and the degradation of GATA3 pre-mRNA. Strikingly, a long noncoding RNA (lncRNA) GATA3-AS, transcribed from the antisense strand of the GATA3 gene, functioned as acis-acting element for the preferential interaction of KIAA1429 with GATA3 pre-mRNA. Accordingly, we found that the tumor growth and metastasis driven by KIAA1429 or GATA3-AS were mediated by GATA3.ConclusionOur study proposed a complex KIAA1429-GATA3 regulatory model based on m6A modification and provided insights into the epi-transcriptomic dysregulation in hepatocarcinogenesis and metastasis.
A client-centered relational framework on barriers to the integration of HIV and substance use services: a systematic review
Authors: Pinto Rogério Meireles , Chen Yun , Park Sunggeun ( Ethan) 
Published: December 2019

AbstractBackgroundGiven the close connection between human immunodeficiency virus (HIV) infection and substance use disorder (SUD), access to integrated HIV and SUD services is critical for individuals experiencing both challenges and their biopsychosocial conditions.MethodAdopting an integrative method, this systematic review included 23 empirical studies published between 2000 and 2018. Articles investigated providers’ and clients’ perspectives on barriers to accessing integrated HIV and SUD services in various service settings (e.g., HIV primary care, SUD treatment, pharmacy).ResultsUsing a client-centered relational framework, we identified barriers in three relational domains with “the client” as the focus of each: client-provider, client-organization, and client-system. The review shows that (1) barriers to HIV and SUD services do not exist in isolation, but in the dynamics within and across three relational domains; (2) service providers and clients often have different perceptions about what constitutes a barrier and the origin of such barriers; and (3) interprofessional and interorganizational collaborations are crucial for integrating HIV and SUD services.ConclusionThis review points out the limitations of the conventional paradigm grouping barriers to service integration into isolated domains (client, provider, organization, or system). Reforms in service arrangements and provider training are recommended to address barriers to integrated services.
Development and validation of a prognostic nomogram for predicting early recurrence after curative resection of stage II/III gastric cancer
Authors: Ma Min , Xiao Haifan , Li Liang , Yin Xianli , Zhou Huijun , Quan Hu , Ouyang Yongzhong , Huang Gang , Li Xiaorong , Xiao Hua 
Published: December 2019

Abstract
Background
The biological behavior of early recurrence is more invasive and the prognosis is worse in gastric cancer (GC). The risk of early recurrence (ER) for GC in stage II/III has not been reported of which the majority of GC patients are in China. Therefore, it is necessary to analyze the ER of gastric cancer in stage II/III.

Methods
The medical records of 1511 consecutive stage II/III GC patients who received resections were retrospectively reviewed. They were randomly classified into either a development or validation group at a ratio of 7:3. The nomogram was constructed based on prognostic factors using logistic regression analysis and was validated by bootstrap resampling and validation dataset, respectively. Concordance index (C-index) values and calibration curves were used to evaluate the predictive accuracy and discriminatory capability.

Results
Three hundred eleven patients experienced ER, accounting for 20.58% of the GC patients investigated. Multivariate logistic regression analysis identified tumors located at upper, middle third, or mixed, a positive lymph node ratio ≥ 0.335, pTNM stage III, lymphocyte count < 1.5 × 109/L, postoperative infection complications and adjuvant chemotherapy < 6 cycles were all independent predictors for ER after curative resection of stage II/III GC. The C-index value obtained for the model was 0.780 (95% CI, 0.747–0.813), and the calibration curves of validation group yielded a C-index value of 0.739 (95% CI, 0.684–0.794), suggesting the practicability of the model.

Conclusions
The nomogram which was developed for predicting ER of stage II/III GC after surgery had good accuracy and was verified through both internal and external validation. The nomogram established can assist clinicians in determining the optimal therapy strategies in counseling, adjuvant treatments, and subsequent follow-up planning.
Fluorescent analysis of boar sperm capacitation process in vitro
Authors: Ded Lukas , Dostalova Pavla , Zatecka Eva , Dorosh Andrej , Komrskova Katerina , Peknicova Jana 
Published: December 2019

Abstract
Background
Capacitation involves physiological changes that spermatozoa must undergo in the female reproductive tract or in vitro to obtain the ability to bind, penetrate and fertilize the egg. Up to date, several methods have been developed to characterize this complex biological process. The goal of the presented study is to mutually compare several fluorescent techniques, check their ability to detect changes in molecular processes during the capacitation progress and determine their ability to predict the percentage of acrosome reacted (AR) sperm after the exposure to solubilized zona pellucida (ZP). The capacitation process was analyzed using four fluorescent techniques: 1. chlortetracycline (CTC) staining, 2. anti-acrosin antibody (ACR.2) assay, 3. anti-phosphotyrosine (pY) antibody assay, 4. fluorescein isothiocyanate-conjugated phalloidin (FITC-phall) assay. All these methods were tested using fluorescent microscopy and flow cytometry.

Results
All selected methods are capable to detect the capacitation progress of boar sperm in vitro, but there are significant differences in their outcome when using fluorescent microscopy or flow cytometry experimental arrangements and subsequent statistical analysis (KW-ANOVA). Also, the ability to predict the absolute numbers of sperm which will undergo ZP-induced AR differ significantly (CTC and ACR.2 gave the best predictions).

Conclusions
Our study compared four largely used methods used to characterize capacitation process, highlighted their differences and showed that all are able to detect capacitation progress, CTC and ACR.2 are furthermore able to accurately predict the percentage of AR sperm after ZP-induced AR.
The effects of small-scale physical and social environmental interventions on walking behaviour among Dutch older adults living in deprived neighbourhoods: results from the quasi-experimental NEW.ROADS study
Authors: Prins R. G. , Kamphuis C. B. M. , Van Lenthe F. J. 
Published: December 2019

Abstract
Purpose
Improving the physical and social conditions of residential neighbourhoods may increase walking, especially among older people. Evidence on the effects of physical and social environmental interventions, and particularly the combination of both, on walking behaviour is scarce. We evaluated the effects of a small-scale physical environmental intervention (designated walking route), a social environmental intervention (neighbourhood walking group) and the combination of both on walking behaviour of older adults living in deprived neighbourhoods.

Methods
Survey data of 644 older adults residing in four deprived neighbourhoods of Rotterdam, the Netherlands, were used to compare changes in walking behaviour over time (weekly minutes spent recreational walking, utilitarian walking and total walking) of those exposed to 1) a designated walking route (physical condition), 2) walking groups (social condition), 3) walking routes and walking groups (combined condition), and 4) no intervention (control condition). Measurements took place at baseline (T0), and 3 months (T1) and 9 months (T2) after the intervention. Data were analysed on a multiple imputed dataset, using multi-level negative binomial regression models, adjusting for clustering of observations within individuals. All models were adjusted for demographic covariates.

Results
Total time spent walking per week increased between T0 and T1 for all conditions. The Incidence Rate Ratio (IRR) for the physical condition was 1.46 (95% CI:1.06;2.05) and for the social intervention 1.52 (95%CI:1.07;2.16). At T2, these differences remained significant for the physical condition, but not for the social condition and the combined condition. These findings were mirrored for utilitarian walking. No evidence was found for an effect on recreational walking.

Conclusion
Implementing small scale, feasible, interventions in a residential neighbourhood may increase total and utilitarian walking behaviour among older adults.
Effect of workplace physical activity interventions on the cardio-metabolic health of working adults: systematic review and meta-analysis
Authors: Mulchandani Rubina , Chandrasekaran Ambalam M. , Shivashankar Roopa , Kondal Dimple , Agrawal Anurag , Panniyammakal Jeemon , Tandon Nikhil , Prabhakaran Dorairaj , Sharma Meenakshi , Goenka Shifalika 
Published: December 2019

Abstract
Background
Adults in urban areas spend almost 77% of their waking time being inactive at workplaces, which leaves little time for physical activity. The aim of this systematic review and meta-analysis was to synthesize evidence for the effect of workplace physical activity interventions on the cardio-metabolic health markers (body weight, waist circumference, body mass index (BMI), blood pressure, lipids and blood glucose) among working adults.

Methods
All experimental studies up to March 2018, reporting cardio-metabolic worksite intervention outcomes among adult employees were identified from PUBMED, EMBASE, COCHRANE CENTRAL, CINAHL and PsycINFO. The Cochrane Risk of Bias tool was used to assess bias in studies. All studies were assessed qualitatively and meta-analysis was done where possible. Forest plots were generated for pooled estimates of each study outcome.

Results
A total of 33 studies met the eligibility criteria and 24 were included in the meta-analysis. Multi-component workplace interventions significantly reduced body weight (16 studies; mean diff: − 2.61 kg, 95% CI: − 3.89 to − 1.33) BMI (19 studies, mean diff: − 0.42 kg/m2, 95% CI: − 0.69 to − 0.15) and waist circumference (13 studies; mean diff: − 1.92 cm, 95% CI: − 3.25 to − 0.60). Reduction in blood pressure, lipids and blood glucose was not statistically significant.

Conclusions
Workplace interventions significantly reduced body weight, BMI and waist circumference. Non-significant results for biochemical markers could be due to them being secondary outcomes in most studies. Intervention acceptability and adherence, follow-up duration and exploring non-RCT designs are factors that need attention in future research.
Prospero registration number: CRD42018094436.
The legacy of Malcolm Beverley Segal (1937–2019) on the science and fields concerned with choroid plexus and cerebrospinal fluid physiology
Authors: Chodobski Adam , Ghersi-Egea Jean-François , Preston-Kennedy Jane , Redzic Zoran , Strazielle Nathalie , Szmydynger-Chodobska Joanna , Thorne Robert G. 
Published: December 2019

AbstractThis article highlights the scientific achievements, professional career, and personal interactions of Malcolm B. Segal who passed away in July this year. Born in 1937 in Goodmayes, Essex, UK, Segal rose to the Chairman position in the Division of Physiology at United Medical and Dental School of Guy’s and St. Thomas’ Hospitals, retiring in 2006 after his long professional career in biomedical science. Being trained in Hugh Davson’s laboratory, Segal became one of the pioneers in research on cerebrospinal fluid physiology and the choroid plexus. During the course of his career, Segal himself trained a number of young scientists and collaborated with many colleagues around the world, making long-lasting friendships along the way. In addition to his professional accomplishments as a researcher and educator, Segal was an avid sailor and wine connoisseur, and enjoyed teaching classes on navigation and wine tasting.
MicroRNA-937 is overexpressed and predicts poor prognosis in patients with colon cancer
Authors: Liu Huiya , Ma Lin , Wang Ling , Yang Yizuo 
Published: December 2019

Abstract
Background
Colon cancer is a heterogeneous tumor and a leading cause of cancer-related mortality. MicroRNA (miRNA) has been proposed as the biomarker in cancers. The aim of this study was to investigate the clinical significance and potential functional role of miR-937 in colon cancer.

Methods
In the present study, reverse transcription-quantitative polymerase chain reaction (qRT-PCR) was conducted to examine the expression levels of miR-937 in colon cancer tissues and cell lines. Kaplan-Meier curve and Cox regression analyses were used to determine the prognostic impact of miR-937 on survival. Cell Counting Kit-8 and Transwell assays were performed to examine cell proliferation, migration, and invasion, respectively.

Results
miR-937 was significantly upregulated in colon cancer tissues and cell lines. Clinical analysis results showed that miR-937 expression was associated with lymph node metastasis and TNM stage. Patients with high miR-937 expression predicted a shorter overall survival rate. Functionally, overexpression of miR-937 promoted cell proliferation, migration, and invasion, while inhibition of miR-937 inhibited these cellular behaviors in vitro.

Conclusions
These results suggested that miR-937 may act as a prognostic biomarker and a potential target for therapeutic strategy, as well as promote proliferation, migration, and invasion of colon cancer.
Excitotoxic glutamate causes neuronal insulin resistance by inhibiting insulin receptor/Akt/mTOR pathway
Authors: Pomytkin Igor , Krasil’nikova Irina , Bakaeva Zanda , Surin Alexander , Pinelis Vsevolod 
Published: December 2019

AbstractAimAn impaired biological response to insulin in the brain, known as central insulin resistance, was identified during stroke and traumatic brain injury, for which glutamate excitotoxicity is a common pathogenic factor. The exact molecular link between excitotoxicity and central insulin resistance remains unclear. To explore this issue, the present study aimed to investigate the effects of glutamate-evoked increases in intracellular free Ca2+concentrations [Ca2+]iand mitochondrial depolarisations, two key factors associated with excitotoxicity, on the insulin-induced activation of the insulin receptor (IR) and components of the Akt/ mammalian target of rapamycin (mTOR) pathway in primary cultures of rat cortical neurons.MethodsChanges in [Ca2+]iand mitochondrial inner membrane potentials (ΔΨm) were monitored in rat cultured cortical neurons, using the fluorescent indicators Fura-FF and Rhodamine 123, respectively. The levels of active, phosphorylated signalling molecules associated with the IR/Akt/mTOR pathway were measured with the multiplex fluorescent immunoassay.ResultsWhen significant mitochondrial depolarisations occurred due to glutamate-evoked massive influxes of Ca2+into the cells, insulin induced 48% less activation of the IR (assessed by IR tyrosine phosphorylation, pY1150/1151), 72% less activation of Akt (assessed by Akt serine phosphorylation, pS473), 44% less activation of mTOR (assessed by mTOR pS2448), and 38% less inhibition of glycogen synthase kinase β (GSK3β) (assessed by GSK3β pS9) compared with respective controls. These results suggested that excitotoxic glutamate inhibits signalling via the IR/Akt/mTOR pathway at multiple levels, including the IR, resulting in the development of acute neuronal insulin resistance within minutes, as an early pathological event associated with excitotoxicity.
MYCN and PRC1 cooperatively repress docosahexaenoic acid synthesis in neuroblastoma via ELOVL2
Authors: Ding Yi , Yang Jie , Ma Yawen , Yao Tengteng , Chen Xingyu , Ge Shengfang , Wang Lihua , Fan Xianqun 
Published: December 2019

Abstract
Background
The MYCN amplification is a defining hallmark of high-risk neuroblastoma. Due to irregular oncogenes orchestration, tumor cells exhibit distinct fatty acid metabolic features from non-tumor cells. However, the function of MYCN in neuroblastoma fatty acid metabolism reprogramming remains unknown.

Methods
Gas Chromatography-Mass Spectrometer (GC-MS) was used to find the potential target fatty acid metabolites of MYCN. Real-time PCR (RT-PCR) and clinical bioinformatics analysis was used to find the related target genes. The function of the identified target gene ELOVL2 on cell growth was detected through CCK-8 assay, Soft agar colony formation assay, flow Cytometry assay and mouse xenograft. Chromatin immunoprecipitation (ChIP) and Immunoprecipitation-Mass Spectrometer (IP-MS) further identified the target gene and the co-repressor of MYCN.

Results
The fatty acid profile of MYCN-depleted neuroblastoma cells identified docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid with anti-tumor activity, significantly increased after MYCN depletion. Compared with MYCN single-copy neuroblastoma cells, DHA level was significantly lower in MYCN-amplified neuroblastoma cells. RT-PCR and clinical bioinformatics analysis discovered that MYCN interfered DHA accumulation via ELOVL fatty acid elongase 2 (ELOVL2) which is a rate-limiting enzyme of cellular DHA synthesis. Enforced ELOVL2 expression in MYCN-amplified neuroblastoma cells led to decreased cell growth and counteracted the growth-promoting effect of MYCN overexpression both in vitro and vivo. ELOVL2 Knockdown showed the opposite effect in MYCN single-copy neuroblastoma cells. In primary neuroblastoma, high ELOVL2 transcription correlated with favorable clinical tumor biology and patient survival. The mechanism of MYCN-mediated ELOVL2 inhibition contributed to epigenetic regulation. MYCN recruited PRC1 (Polycomb repressive complex 1), catalysed H2AK119ub (histone 2A lysine 119 monoubiquitination) and inhibited subsequent ELOVL2 transcription.

Conclusions
The tumor suppressive properties of DHA and ELOVL2 are repressed by the MYCN and PRC1 jointly, which suggests a new epigenetic mechanism of MYCN-mediated fatty acid regulation and indicates PRC1 inhibition as a potential novel strategy to activate ELOVL2 suppressive functions.
A longitudinal study highlights shared aspects of the transcriptomic response to cardiogenic and septic shock
Authors: Braga Daniele , Barcella Matteo , Herpain Antoine , Aletti Federico , Kistler Erik B. , Bollen Pinto Bernardo , Bendjelid Karim , Barlassina Cristina 
Published: December 2019

AbstractBackgroundSeptic shock (SS) and cardiogenic shock (CS) are two types of circulatory shock with a different etiology. Several studies have described the molecular alterations in SS patients, whereas the molecular factors involved in CS have been poorly investigated. We aimed to assess in the whole blood of CS and SS patients, using septic patients without shock (SC) as controls, transcriptomic modifications that occur over 1 week after ICU admission and are common to the two types of shock.MethodsWe performed whole blood RNA sequencing in 21 SS, 11 CS, and 5 SC. In shock patients, blood samples were collected within 16 h from ICU admission (T1), 48 h after ICU admission (T2), and at day 7 or before discharge (T3). In controls, blood samples were available at T1 and T2. Gene expression changes over time have been studied in CS, SS, and SC separately with a paired analysis. Genes withpvalue < 0.01 (Benjamini-Hochberg multiple test correction) were defined differentially expressed (DEGs). We used gene set enrichment analysis (GSEA) to identify the biological processes and transcriptional regulators significantly enriched in both types of shock.ResultsIn both CS and SS patients, GO terms of inflammatory response and pattern recognition receptors (PRRs) were downregulated following ICU admission, whereas gene sets of DNA replication were upregulated. At the gene level, we observed that alarmins, interleukin receptors, PRRs, inflammasome, and DNA replication genes significantly changed their expression in CS and SS, but not in SC. Analysis of transcription factor targets showed in both CS and SS patients, an enrichment of CCAAT-enhancer-binding protein beta (CEBPB) targets in genes downregulated over time and an enrichment of E2F targets in genes with an increasing expression trend.ConclusionsThis pilot study supports, within the limits of a small sample size, the role of alarmins, PRRs, DNA replication, and immunoglobulins in the pathophysiology of circulatory shock, either in the presence of infection or not. We hypothesize that these genes could be potential targets of therapeutic interventions in CS and SS.Trial registrationClinicalTrials.gov,NCT02141607. Registered 19 May 2014.