bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of HIV infection on tuberculosis transmission in a country with low tuberculosis incidence: a national retrospective study using molecular epidemiology
Authors: Winter Joanne R. , Smith Colette J. , Davidson Jennifer A. , Lalor Maeve K. , Delpech Valerie , Abubakar Ibrahim , Stagg Helen R. 
Published: December 2020

Abstract
Background
HIV is known to increase the likelihood of reactivation of latent tuberculosis to active TB disease; however, its impact on tuberculosis infectiousness and consequent transmission is unclear, particularly in low-incidence settings.

Methods
National surveillance data from England, Wales and Northern Ireland on tuberculosis cases in adults from 2010 to 2014, strain typed using 24-locus mycobacterial-interspersed-repetitive-units–variable-number-tandem-repeats was used retrospectively to identify clusters of tuberculosis cases, subdivided into ‘first’ and ‘subsequent’ cases.
Firstly, we used zero-inflated Poisson regression models to examine the association between HIV status and the number of subsequent clustered cases (a surrogate for tuberculosis infectiousness) in a strain type cluster. Secondly, we used logistic regression to examine the association between HIV status and the likelihood of being a subsequent case in a cluster (a surrogate for recent acquisition of tuberculosis infection) compared to the first case or a non-clustered case (a surrogate for reactivation of latent infection).

Results
We included 18,864 strain-typed cases, 2238 were the first cases of clusters and 8471 were subsequent cases. Seven hundred and fifty-nine (4%) were HIV-positive.
Outcome 1: HIV-positive pulmonary tuberculosis cases who were the first in a cluster had fewer subsequent cases associated with them (mean 0.6, multivariable incidence rate ratio [IRR] 0.75 [0.65–0.86]) than those HIV-negative (mean 1.1).
Extra-pulmonary tuberculosis (EPTB) cases with HIV were less likely to be the first case in a cluster compared to HIV-negative EPTB cases. EPTB cases who were the first case had a higher mean number of subsequent cases (mean 2.5, IRR (3.62 [3.12–4.19]) than those HIV-negative (mean 0.6).
Outcome 2: tuberculosis cases with HIV co-infection were less likely to be a subsequent case in a cluster (odds ratio 0.82 [0.69–0.98]), compared to being the first or a non-clustered case.

Conclusions
Outcome 1: pulmonary tuberculosis-HIV patients were less infectious than those without HIV. EPTB patients with HIV who were the first case in a cluster had a higher number of subsequent cases and thus may be markers of other undetected cases, discoverable by contact investigations.
Outcome 2: tuberculosis in HIV-positive individuals was more likely due to reactivation than recent infection, compared to those who were HIV-negative.
Blood leukocyte composition and function in periparturient ewes kept on different dietary magnesium supply
Authors: Ahmed Mona H. , Wilkens Mirja R. , Möller Bernd , Ganter Martin , Breves Gerhard , Schuberth Hans-Joachim 
Published: December 2020

Abstract
Background
Transition period (TP) is characterised by physiological and metabolic changes contributing to immunodysregulation. Since knowledge about this period in sheep is scarce, we analysed changes in selected immune variables during the TP in ewes and whether dietary magnesium (Mg) supplementation could modulate these immune variables. Pregnant ewes (2nd and 3rd lactation) were divided into a control group (CONT, n = 9) and a Mg group (MAG, n = 10) supplemented with Mg oxide resulting in a daily Mg intake of approximately 0.30 and 0.38% (MAG) of dry matter during ante- (a.p.) and post-partum (p.p.) periods, respectively. Blood samples were collected between days (d) 30 a.p. and d 30 p.p.. Whole blood neutrophil phagocytic activity, monocyte subset (classical cM, intermediate intM, non-classical ncM) composition and the proliferative capacity of lymphocytes were determined flow cytometrically. At d 14 a.p., all ewes were vaccinated against Mycobacterium avium subsp. paratuberculosis (MAP).

Results
Both groups showed a sharp increase in the total leukocyte counts (TLC) and neutrophil counts (P < 0.0001), at d 1 p.p., while, monocytes and their subpopulations displayed the highest values at d 30 p.p. (P ≤ 0.05). At d 1 p.p. the neutrophil phagocytic activity was higher (P < 0.05) in MAG ewes. Throughout the TP, the proliferative response of CD4+ cells was significantly higher in the MAG group (P < 0.05). Ewes in both groups responded with an increase in the TLC, neutrophil numbers (P ≤ 0.05) and ncM (P < 0.001) 24 h post vaccination, whereas monocytes and cM dropped in numbers (P ≤ 0.05). Numbers of intM only increased in MAG ewes (P < 0.05), whereas lymphocyte numbers decreased (P < 0.01). Mg supplementation did not affect the significant increase in MAP-specific antibodies at d 7 and 21 post vaccination. Total Mg and Ca serum levels did not show any differences between the two groups.

Conclusion
Whereas TP-associated fluctuations in blood leukocyte numbers are not influenced by Mg supplementation, neutrophil phagocytic activity, the proliferative capacity of CD4+ cells and the cellular response within 24 h after a vaccination are subject to modulation.
Manipulating the position of DNA expression cassettes using location tags fused to dCas9 (Cas9-Lag) to improve metabolic pathway efficiency
Authors: Xie Qianwen , Li Siwei , Zhao Dongdong , Ye Lijun , Li Qingyan , Zhang Xueli , Zhu Li , Bi Changhao 
Published: December 2020

Abstract
Background
Deactivated Cas9 (dCas9) led to significant improvement of CRISPR/Cas9-based techniques because it can be fused with a variety of functional groups to form diverse molecular devices, which can manipulate or modify target DNA cassettes. One important metabolic engineering strategy is to localize the enzymes in proximity of their substrates for improved catalytic efficiency. In this work, we developed a novel molecular device to manipulate the cellular location of specific DNA cassettes either on plasmids or on the chromosome, by fusing location tags to dCas9 (Cas9-Lag), and applied the technique for synthetic biology applications. Carotenoids like β-carotene serve as common intermediates for the synthesis of derivative compounds, which are hydrophobic and usually accumulate in the membrane compartment.

Results
Carotenoids like β-carotene serve as common intermediates for the synthesis of derivative compounds, which are hydrophobic and usually accumulate in the membrane components. To improve the functional expression of membrane-bound enzymes and localize them in proximity to the substrates, Cas9-Lag was used to pull plasmids or chromosomal DNA expressing carotenoid enzymes onto the cell membrane. For this purpose, dCas9 was fused to the E. coli membrane docking tag GlpF, and gRNA was designed to direct this fusion protein to the DNA expression cassettes. With Cas9-Lag, the zeaxanthin and astaxanthin titer increased by 29.0% and 26.7% respectively. Due to experimental limitations, the electron microscopy images of cells expressing Cas9-Lag vaguely indicated that GlpF-Cas9 might have pulled the target DNA cassettes in close proximity to membrane. Similarly, protein mass spectrometry analysis of membrane proteins suggested an increased expression of carotenoid-converting enzymes in the membrane components.

Conclusion
This work therefore provides a novel molecular device, Cas9-Lag, which was proved to increase zeaxanthin and astaxanthin production and might be used to manipulate DNA cassette location.
RETRACTED ARTICLE: GPX8 is transcriptionally regulated by FOXC1 and promotes the growth of gastric cancer cells through activating the Wnt signaling pathway
Authors: Chen Hong , Xu Lu , Shan Zhi-li , Chen Shu , Hu Hao 
Published: December 2020

Abstract
Background
Glutathione Peroxidase 8 (GPX8) as a member of the glutathione peroxidase (GPx) family plays an important role in anti-oxidation. Besides, dysregulation of GPX8 has been found in gastric cancer, but its detailed molecular mechanism in gastric cancer has not been reported.

Methods
Our study detected the expression of GPX8 in gastric cancer tissues and cell lines using immunohistochemistry (IHC), western blot and qRT-PCR, and determined the effect of GPX8 on gastric cancer cells using CCK-8, colony formation, transwell migration and invasion assays. Besides, the effect of GPX8 on the Wnt signaling pathway was determined by western blot. Furthermore, the transcription factor of GPX8 was identified by bioinformatics methods, dual luciferase reporter and chromatin immunoprecipitation (CHIP) assays. In addition, the effect of GPX8 on tumor formation was measured by IHC and western blot.

Results
The over-expression of GPX8 was observed in gastric cancer tissues and cells, which facilitated the proliferation, migration and invasion of gastric cancer cells as well as the tumor growth. GPX8 knockdown effectively inhibited the growth of gastric cancer cells and tumors. Moreover, GPX8 could activate the Wnt signaling pathway to promote the cellular proliferation, migration and invasion through. Furthermore, FOXC1 was identified as a transcription factor of GPX8 and mediated GPX8 expression to affect cell development processes.

Conclusions
These findings contribute to understanding the molecular mechanism of GPX8 in gastric cancer. Additionally, GPX8 can be a potential biomarker for gastric cancer therapy.
Musashi-1 promotes cancer stem cell properties of glioblastoma cells via upregulation of YTHDF1
Authors: Yarmishyn Aliaksandr A. , Yang Yi-Ping , Lu Kai-Hsi , Chen Yi-Chen , Chien Yueh , Chou Shih-Jie , Tsai Ping-Hsing , Ma Hsin-I. , Chien Chian-Shiu , Chen Ming-Teh , Wang Mong-Lien 
Published: December 2020

Abstract
Background
Glioblastoma (GBM) is the most lethal brain tumor characterized by high morbidity and limited treatment options. Tumor malignancy is usually associated with the epigenetic marks, which coordinate gene expression to ascertain relevant phenotypes. One of such marks is m6A modification of RNA, whose functional effects are dependent on the YTH family m6A reader proteins.

Methods and results
In this study, we investigated the expression of five
YTH family proteins in different GBM microarray datasets from the Oncomine
database, and identified YTHDF1 as the most highly overexpressed member of this
family in GBM. By performing the knockdown of YTHDF1 in a GBM cell line, we
found that it positively regulates proliferation, chemoresistance and cancer
stem cell-like properties. Musashi-1 (MSI1) is a postranscriptional gene
expression regulator associated with high oncogenicity in GBM. By knocking down
and overexpressing MSI1, we found that it positively regulates YTHDF1
expression. The inhibitory effects
imposed on the processes of proliferation and migration by YTHDF1 knockdown
were shown to be partially rescued by concomitant overexpression of MSI1. MSI1
and YTHDF1 were shown to be positively correlated in clinical glioma samples,
and their concomitant upregulation was associated with decreased survival of
glioma patients. We identified the direct regulation of YTHDF1 by MSI1.

Conclusions
Given the fact that both proteins are master
regulators of gene expression, and both of them are unfavorable factors in GBM,
we suggest that in any future studies aimed to uncover the prognostic value and
therapy potential, these two proteins should be considered together.
Antimicrobial coating is associated with significantly lower aerobic colony counts in high-touch areas in an orthopedic ward environment
Authors: Ejerhed Lars , Roshani Leyla , Andersson Annette Erichsen 
Published: December 2020

Abstract
Background
Hospital acquired infections (HAI) are the most common complication found in the hospital environment. The aim of the study was to examine whether the use of an antimicrobial coating in high-touch areas in an orthopedic ward could reduce bacterial growth and HAI.

Methods

From December 2017 to February 2018, HAI were registered on two orthopedic wards. A second registration was performed from December 2018 to February 2019. On the second occasion, an antimicrobial organosilane coating was applied just before the study period and thereafter weekly on one ward, while the other ward served as a control. Twenty defined high-touch areas on each ward were cultured before treatment and after 1, 2, 4, 8, 12, 14 and 16 weeks. Samples were cultured for aerobic colony counts, Staphylococcus aureus and E. coli.

Results
The total aerobic colony counts were 47% lower on the treated ward compared with the non-treated ward over the study period (p = 0.02). The colony counts for Staphylococcus aureus and E. coli were low on both wards. During the first registration period, the incidence of HAI was 22.7% and 20.0% on the non-treated and subsequently treated ward respectively. On the second occasion, after treatment, the incidence was 25.0% and 12.5% (treated ward) respectively (p = 0.0001).

Conclusions
The use of a long-lasting antimicrobial organosilane coating appears to reduce the bioburden and reduce HAI. Since the incidence of HAI varies substantially over time, longer observation times are needed.
Microtubule cytoskeleton-disrupting activity of MWCNTs: applications in cancer treatment
Authors: Hevia Lorena García , Fanarraga Mónica L. 
Published: December 2020

AbstractMicrotubules and carbon nanotubes (CNTs), and more particularly multi-walled CNTs (MWCNTs), share many mechanical and morphological similarities that prompt their association into biosynthetic tubulin filaments both, in vitro and in vivo. Unlike CNTs, microtubules are highly dynamic protein polymers that, upon interaction with these nanomaterials, display enhanced stability that has critical consequences at the cellular level. Among others, CNTs prompt ectopic (acentrosomal) microtubule nucleation and the disassembly of the centrosome, causing a dramatic cytoskeletal reorganization. These changes in the microtubule pattern trigger the generation of ineffective biomechanical forces that result in migration defects, and ultimately in spindle-assembly checkpoint (SAC) blockage and apoptosis. In this review, we describe the molecular mechanism involved in the intrinsic interference of CNTs with the microtubule dynamics and illustrate the consequences of this effect on cell biomechanics. We also discuss the potential application of these synthetic microtubule-stabilizing agents as synergetic agents to boost the effect of classical chemotherapy that includes spindle poisons (i.e. paclitaxel) or DNA interfering agents (5-fluorouracil)-, and list some of the advantages of the use of MWCNTs as adjuvant agents in preventing cell resistance to chemotherapy.
The effectiveness of pediatric obesity prevention policies: a comprehensive systematic review and dose–response meta-analysis of controlled clinical trials
Authors: Taghizadeh Shahnaz , Farhangi Mahdieh Abbasalizad 
Published: December 2020

AbstractBackgroundChildhood obesity persists as a serious public health problem. In the current meta-analysis, we summarized the results of controlled trials that evaluated the effect of obesity prevention policies in children and adolescents.MethodsThree databases (SCOPUS, PubMed and Embase) were searched for studies published before the 6th April 2020, by reported outcome measures of body mass index (BMI) and BMI-Zscore. Forty-seven studies reported BMI, while 45 studies reported BMI-Zscoreas final outcome.ResultsThe results showed that the obesity-prevention policies had significant effect in reducing BMI (WMD: − 0.127; CI − 0.198, − 0.056; P < 0.001). These changes were not significant for BMI-Zscore(WMD: − 0.020; CI − 0.061, 0.021; P = 0.340). In dose–response meta-analysis, a non-linear association was reported between the duration of intervention and BMI (Pnonlinearity < 0.001) as well as BMI-Zscore(Pnonlinearity = 0.023). In subgroup analysis, the more favorite results were observed for 5–10 years old, with combination of physical activity and diet as intervention materials.ConclusionIn conclusion, the obesity prevention policies in short-term periods of less than 2 years, in rather early age of school with approaches of change in both of diet and physical activity, could be more effective in prevention of childhood obesity.Trial registrationPROSPERO registration number: CRD42019138359
Co-expression of cancer driver genes: IDH-wildtype glioblastoma-derived tumorspheres
Authors: Yoon Seon-Jin , Son Hye Young , Shim Jin-Kyoung , Moon Ju Hyung , Kim Eui-Hyun , Chang Jong Hee , Teo Wan Yee , Kim Se Hoon , Park Sahng Wook , Huh Yong-Min , Kang Seok-Gu 
Published: December 2020

Abstract
Background
Driver genes of GBM may be crucial for the onset of isocitrate dehydrogenase (IDH)-wildtype (WT) glioblastoma (GBM). However, it is still unknown whether the genes are expressed in the identical cluster of cells. Here, we have examined the gene expression patterns of GBM tissues and patient-derived tumorspheres (TSs) and aimed to find a progression-related gene.

Methods
We retrospectively collected primary IDH-WT GBM tissue samples (n = 58) and tumor-free cortical tissue samples (control, n = 20). TSs are isolated from the IDH-WT GBM tissue with B27 neurobasal medium. Associations among the driver genes were explored in the bulk tissue, bulk cell, and a single cell RNAsequencing techniques (scRNAseq) considering the alteration status of TP53, PTEN, EGFR, and TERT promoter as well as MGMT promoter methylation. Transcriptomic perturbation by temozolomide (TMZ) was examined in the two TSs.

Results
We comprehensively compared the gene expression of the known driver genes as well as MGMT, PTPRZ1, or IDH1. Bulk RNAseq databases of the primary GBM tissue revealed a significant association between TERT and TP53 (p < 0.001, R = 0.28) and its association increased in the recurrent tumor (p  < 0.001, R = 0.86). TSs reflected the tissue-level patterns of association between the two genes (p < 0.01, R = 0.59, n = 20). A scRNAseq data of a TS revealed the TERT and TP53 expressing cells are in a same single cell cluster. The driver-enriched cluster dominantly expressed the glioma-associated long noncoding RNAs. Most of the driver-associated genes were downregulated after TMZ except IGFBP5.

Conclusions
GBM tissue level expression patterns of EGFR, TERT, PTEN, IDH1, PTPRZ1, and MGMT are observed in the GBM TSs. The driver gene-associated cluster of the GBM single cells were enriched with the glioma-associated long noncoding RNAs.
Potential causal factors of CFS/ME: a concise and systematic scoping review of factors researched
Authors: Muller Ashley Elizabeth , Tveito Kari , Bakken Inger Johanne , Flottorp Signe A. , Mjaaland Siri , Larun Lillebeth 
Published: December 2020

Abstract
Background
Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is understood as a complex condition, likely triggered and sustained by an interplay of biological, psychological, and social factors. Little oversight exists of the field of causal research. This systematic scoping review explores potential causal factors of CFS/ME as researched by primary studies.

Methods
We searched eight databases for primary studies that examined potential causal factors of CFS/ME. Based on title/abstract review, two researchers independently sorted each study’s factors into nine main categories and 71 subordinate categories, using a system developed with input given during a 2018 ME conference, specialists and representatives from a ME patient advocacy group, and using BMJ Best Practice’s description of CFS/ME etiology. We also extracted data related to study design, size, diagnostic criteria and comparison groups.

Results
We included 1161 primary studies published between January 1979 and June 2019. Based on title/abstract analysis, no single causal factor dominated in these studies, and studies reported a mean of 2.73 factors. The four most common factors were: immunological (297 studies), psychological (243), infections (198), and neuroendocrinal (198). The most frequent study designs were case–control studies (894 studies) comparing CFS/ME patients with healthy participants. More than half of the studies (that reported study size in the title/abstract) included 100 or fewer participants.

Conclusion
The field of causal hypotheses of CFS/ME is diverse, and we found that the studies examined all the main categories of possible factors that we had defined a priori. Most studies were not designed to adequately explore causality, rather to establish hypotheses. We need larger studies with stronger study designs to gain better knowledge of causal factors of CFS/ME.
Minocycline reduces inflammatory response and cell death in a S100B retina degeneration model
Authors: Grotegut Pia , Perumal Natarajan , Kuehn Sandra , Smit Andreas , Dick H. Burkhard , Grus Franz H. , Joachim Stephanie C. 
Published: December 2020

Abstract
Background
Previous studies noted that intravitreal injection of S100B triggered a glaucoma-like degeneration of retina and optic nerve as well as microglia activation after 14 days. The precise role of microglia in our intravitreal S100B model is still unclear. Hence, microglia were inhibited through minocycline. The aim is to investigate whether microglia have a significant influence on the degeneration process or whether they are only a side effect in the model studied here.

Methods
Minocycline was applied daily in rats by intraperitoneal injection using two different concentrations (13.5 mg/kg body weight, 25 mg/kg body weight). One day after treatment start, S100B or PBS was intravitreally injected in one eye per rat. The naïve groups received no injections. This resulted in a total of five groups (naïve n = 14, PBS n = 14, S100B n = 13, 13.5 mg/kg mino n = 15, 25 mg/kg mino n = 15). At day 14, electroretinogram measurements were performed, followed by immunofluorescence and label-free quantitative proteomics analysis. The focus of these investigations was on the survival of RGCs as well as their axons, the response of the microglia, and the identification of further pathological modes of action of S100B.

Results
The best signal transmission was detected via ERG in the 13.5 mg/kg mino group. The inhibition of the microglia protected optic nerve neurofilaments and decreased the negative impact of S100B on RGCs. However, the minocycline treatment could not trigger complete protection of RGCs. Furthermore, in retina and optic nerve, the minocycline treatment reduced the number and activity of S100B-triggered microglia in a concentration-dependent manner. Proteomics analysis showed that S100B application led to numerous metabolic functions and cellular stress, mainly an increased inflammatory response, glycolysis, and mitochondrial dysfunction, which caused oxidative stress in the retina. Importantly, the protective capability of lower dose of minocycline was unraveled by suppressing the apoptotic, inflammatory, and the altered metabolic processes caused by S100B insult in the retina.

Conclusion
Intravitreally injected S100B not only led to a pro-inflammatory microglial reaction, but also a mitochondrial and metabolic dysfunction. Also, these results suggest that an excessive microglial response may be a significant degenerative factor, but not the only trigger for increased cell death.