bluuebunny/crossref_metadata_2025_split huggingface dataset:
DjinniChip: evaluation of a novel molecular rapid diagnostic device for the detection of Chlamydia trachomatis in trachoma-endemic areas
Authors: Derrick Tamsyn R. , Sandetskaya Natalia , Pickering Harry , Kölsch Andreas , Ramadhani Athumani , Mafuru Elias , Massae Patrick , Malisa Aiweda , Mtuy Tara , Burton Matthew J. , Holland Martin J. , Kuhlmeier Dirk 
Published: October 2020

Abstract
Background
The clinical signs of active trachoma are often present in the absence of ocular Chlamydia trachomatis infection, particularly following mass drug administration. Treatment decisions following impact surveys and in post-control surveillance for communities are currently based on the prevalence of clinical signs, which may result in further unnecessary distribution of mass antibiotic treatment and the increased spread of macrolide resistance alleles in ‘off-target’ bacterial species. We therefore developed a simple, fast, low cost diagnostic assay (DjinniChip) for diagnosis of ocular C. trachomatis for use by trachoma control programmes.

Methods
The study was conducted in the UK, Germany and Tanzania. For clinical testing in Tanzania, specimens from a sample of 350 children between the ages of 7 to 15 years, which were part of a longitudinal cohort that began in February 2012 were selected. Two ocular swabs were taken from the right eye. The second swab was collected dry, kept cool in the field and archived at – 80 °C before sample lysis for DjinniChip detection and parallel nucleic acid purification and detection/quantification by qPCR assay.

Results
DjinniChip was able to reliably detect > 10 copies of C. trachomatis per test and correctly identified 7/10 Quality Control for Molecular Diagnostics C. trachomatis panel samples, failing to detect 3 positive samples with genome equivalent amounts ≤ 10 copies. DjinniChip performed well across a range of typical trachoma field conditions and when used by lay personnel using a series of mock samples. In the laboratory in Tanzania, using clinical samples the sensitivity and specificity of DjinniChip for C. trachomatis was 66% (95% CI 51–78) and 94.8 (95% CI 91–97%) with an overall accuracy of 90.1 (95% CI 86.4–93).

Conclusions
DjinniChip performance is extremely promising, particularly its ability to detect low concentrations of C. trachomatis and its usability in field conditions. The DjinniChip requires further development to reduce inhibition and advance toward a closed system. DjinniChip results did not vary between local laboratory results and typical trachoma field settings, illustrating its potential for use in low-resource areas to prevent unnecessary rounds of MDA and to monitor for C. trachomatis recrudescence.
Performance of Ag-ELISA in the diagnosis of Taenia solium cysticercosis in naturally infected pigs in Tanzania
Authors: Kabululu Mwemezi L. , Johansen Maria V. , Mlangwa James E. D. , Mkupasi Ernatus M. , Braae Uffe C. , Trevisan Chiara , Colston Angela , Cordel Claudia , Lightowlers Marshall W. , Ngowi Helena A. 
Published: October 2020

Abstract
Background
Taenia solium is a zoonotic parasite responsible for neurocysticercosis—a major cause of late-onset acquired epilepsy in humans. Lack of affordable, specific and sensitive diagnostic tools hampers control of the parasite. This study assessed the performance of an antigen detection enzyme-linked immunosorbent assay (Ag-ELISA) in the diagnosis of viable T. solium cysticercosis in naturally infected slaughter-age pigs in an endemic area in Tanzania.

Methods
A total of 350 pigs were bled before they were slaughtered and their carcases examined. Serum was analyzed for circulating antigens by using a monoclonal antibody-based B158/B60 Ag-ELISA. Each carcase was examined for the presence of Taenia hydatigena cysticerci and half carcase musculature together with the whole brain, head muscles, tongue, heart and diaphragm were sliced with fine cuts (< 0.5 cm) to reveal and enumerate T. solium cysticerci. Half carcase dissection can detect at least 84% of infected pigs. Prevalence and their 95% confidence intervals (CI) were calculated in Stata 12. Sensitivity, specificity, predictive values and likelihood ratios were determined.

Results
Twenty–nine pigs (8.3%, 95% CI: 5.6–11.7%) had viable T. solium cysticerci while 11 pigs had T. hydatigena cysticerci (3.1%, 95% CI: 1.6–5.5%). No co-infection was observed. Sixty-eight pigs (19.4%, 95% CI: 15.4–20%) tested positive on Ag-ELISA; of these, 24 had T. solium cysticerci and 7 had T. hydatigena cysticerci. Sensitivity and specificity were determined to be 82.7% and 86.3%, respectively. Positive and negative predictive values were 35.2% and 98.2%, respectively. Likelihood ratios for positive and negative Ag-ELISA test results were 6.0 and 0.2, respectively. There was a significant positive correlation between the titre of circulating antigens and intensity of T. solium cysticerci (r(348) = 0.63, P < 0.001).

Conclusions
The Ag-ELISA test characteristics reported in this study indicate that the test is more reliable in ruling out T. solium cysticercosis in pigs, than in confirming it. Hence, a negative result will almost certainly indicate that a pig has no infection, but a positive result should always be interpreted with caution. Estimates of T. solium prevalence based on Ag-ELISA results should, therefore, be adjusted for test performance characteristics and occurrence of T. hydatigena.
Chromatin accessibility dynamics of Chlamydia-infected epithelial cells
Authors: Hayward Regan J. , Marsh James W. , Humphrys Michael S. , Huston Wilhelmina M. , Myers Garry S. A. 
Published: October 2020

AbstractChlamydia are Gram-negative, obligate intracellular bacterial pathogens responsible for a broad spectrum of human and animal diseases. In humans,Chlamydia trachomatisis the most prevalent bacterial sexually transmitted infection worldwide and is the causative agent of trachoma (infectious blindness) in disadvantaged populations. Over the course of its developmental cycle,Chlamydiaextensively remodels its intracellular niche and parasitises the host cell for nutrients, with substantial resulting changes to the host cell transcriptome and proteome. However, little information is available on the impact of chlamydial infection on the host cell epigenome and global gene regulation. Regions of open eukaryotic chromatin correspond to nucleosome-depleted regions, which in turn are associated with regulatory functions and transcription factor binding. We applied formaldehyde-assisted isolation of regulatory elements enrichment followed by sequencing (FAIRE-Seq) to generate temporal chromatin maps ofC. trachomatis-infected human epithelial cells in vitro over the chlamydial developmental cycle. We detected both conserved and distinct temporal changes to genome-wide chromatin accessibility associated withC. trachomatisinfection. The observed differentially accessible chromatin regions include temporally-enriched sets of transcription factors, which may help shape the host cell response to infection. These regions and motifs were linked to genomic features and genes associated with immune responses, re-direction of host cell nutrients, intracellular signalling, cell–cell adhesion, extracellular matrix, metabolism and apoptosis. This work provides another perspective to the complex response to chlamydial infection, and will inform further studies of transcriptional regulation and the epigenome inChlamydia-infected human cells and tissues.
Molecular correlates and therapeutic targets in T cell-inflamed versus non-T cell-inflamed tumors across cancer types
Authors: Bao Riyue , Stapor Daniel , Luke Jason J. 
Published: October 2020

Abstract
Background
The T cell-inflamed tumor microenvironment, characterized by CD8 T cells and type I/II interferon transcripts, is an important cancer immunotherapy biomarker. Tumor mutational burden (TMB) may also dictate response, and some oncogenes (i.e., WNT/β-catenin) are known to mediate immunosuppression.

Methods
We performed an integrated multi-omic analysis of human cancer including 11,607 tumors across multiple databases and patients treated with anti-PD1. After adjusting for TMB, we correlated the T cell-inflamed gene expression signature with somatic mutations, transcriptional programs, and relevant proteome for different immune phenotypes, by tumor type and across cancers.

Results
Strong correlations were noted between mutations in oncogenes and tumor suppressor genes and non-T cell-inflamed tumors with examples including IDH1 and GNAQ as well as less well-known genes including KDM6A, CD11c, and genes with unknown functions. Conversely, we observe genes associating with the T cell-inflamed phenotype including VHL and PBRM1. Analyzing gene expression patterns, we identify oncogenic mediators of immune exclusion across cancer types (HIF1A and MYC) as well as novel examples in specific tumors such as sonic hedgehog signaling, hormone signaling and transcription factors. Using network analysis, somatic and transcriptomic events were integrated. In contrast to previous reports of individual tumor types such as melanoma, integrative pan-cancer analysis demonstrates that most non-T cell-inflamed tumors are influenced by multiple signaling pathways and that increasing numbers of co-activated pathways leads to more highly non-T cell-inflamed tumors. Validating these analyses, we observe highly consistent inverse relationships between pathway protein levels and the T cell-inflamed gene expression across cancers. Finally, we integrate available databases for drugs that might overcome or augment the identified mechanisms.

Conclusions
These results nominate molecular targets and drugs potentially available for further study and potential immediate translation into clinical trials for patients with cancer.
Effects of dapagliflozin on serum and urinary uric acid levels in patients with type 2 diabetes: a prospective pilot trial
Authors: Yuan Tao , Liu Shixuan , Dong Yingyue , Fu Yong , Tang Yan , Zhao Weigang 
Published: October 2020

Abstract
Background
We aimed to evaluate the effects of short-term therapy with dapagliflozin on serum uric acid (SUA) and urinary uric acid (UUA) levels in patients with type 2 diabetes.

Methods
In this prospective pilot trial, 8 patients with type 2 diabetes mellitus were assigned to the treatment group with dapagliflozin 10 mg once daily for one week, and 7 subjects with normal glucose tolerance were recruited into the control group. Data of anthropometric measurements, SUA, 24-h UUA, fractional excretion of UA (FEUA), serum lipid parameters and 3-h oral glucose tolerance test (OGTT) were collected in both treatment and control groups; all examinations were repeated after treatment. The area under the curve of glucose (AUCGlu) was calculated to reflect the general glucose levels, while insulin resistance and islet β-cell function were reflected by indexes calculated according to the data obtained from the OGTT.

Results
The weight and serum lipid parameters showed no differences before and after treatment with dapagliflozin for one week. We found SUA levels decreased from 347.75 ± 7.75 μmol/L before treatment to 273.25 ± 43.18 μmol/L after treatment, with a statistically significant difference (P = 0.001) and was accompanied by a significant increase in FEUA from 0.009 to 0.029 (P = 0.035); there was a linear correlation between SUA and FEUA levels. Glucose control, insulin sensitivity and islet β-cell function were improved to a certain extent. We also found a positive correlation between the decrease in glucose levels and the improvement in islet β-cell function.

Conclusions
The SUA-lowering effect of dapagliflozin could be driven by increasing UA excretion within one week of treatment, and a certain degree of improvement in glucose levels and islet β-cell function were observed.
Trial registration ClinicalTrials.gov identifier, NCT04014192. Registered 12 July 2019, https://www.clinicaltrials.gov/ct2/show/NCT04014192:term=NCT04014192&draw=2&rank=1. Yes.
Risk factors for sexual dysfunction in Romanian women with type 1 diabetes mellitus and chronic autoimmune thyroiditis: a comparative cross-sectional study
Authors: Gherbon Adriana , Frandes Mirela , Roman Deiana , Anastasiu-Popov Diana , Timar Romulus 
Published: October 2020

Abstract
Background
Female sexual dysfunction (FSD) is one of the chronic complications of diabetes as is male sexual dysfunction, but the former is less studied. Therefore, the aim of this study was to assess of the prevalence and risk factors associated with FSD in Romanian women with type 1 diabetes mellitus (T1DM) and chronic autoimmune thyroiditis (CAT).

Methods
The study sample included 104 Romanian women with both T1DM and CAT, and 101 Romanian matched controls with only T1DM. The presence of FSD was established using two validated tests: The Female Sexual Function Index and the Female Sexual Distress Scale-revised. The presence of depression was assessed using Beck’s Depression Inventory-II.

Results
We found that almost half of the women in the group with T1DM and CAT presented with sexual dysfunction (49 vs. 33.7% in the control group; p = 0.025): 27.9 vs. 8.9 (p < 0.001)—desire, 23.1 vs. 7.9% (p = 0.003)—orgasm, 21.2 vs. 5.9% (p = 0.002)—lubrication, 17.3 vs. 6.9% (p = 0.023)—arousal, 9.6 vs. 1% (p = 0.006)—pain, and 20.2 vs. 9.9% (p = 0.040)—satisfaction problems. Multivariate regression analysis revealed that age was a significant risk factor for FSD, along with DM and body mass index. Coexisting CAT, polyneuropathy, depression, and the use of insulin pumps were significant risk factors for FSD.

Conclusions
Women with T1DM and CAT are more likely to present with FSD than those without. It is important for patients to address depression, if present, and exercise caution while using insulin pumps. Moreover, DM complications such as polyneuropathy are significant risk factors for FSD; thus, it is crucial to ensure satisfactory glycemic control and optimal DM management.
Potential role of intestinal microflora in disease progression among patients with different stages of Hepatitis B
Authors: Yang Xiu-An , Lv Fengchun , Wang Ran , Chang Yange , Zhao Yiming , Cui Xinyu , Li Haochen , Yang Sixi , Li Suting , Zhao Xuemin , Mo Zhishuo , Yang Fang 
Published: October 2020

Abstract
Background
Increasing evidence demonstrate that the gut microbiota is involved in the pathogenesis of liver diseases, and faecal microbiota transplantation is considered to be a promising new treatment option. However, there are no reports on the intestinal flora of asymptomatic HBV carriers using next-generation sequencing. This study intends to investigate the potential role of the intestinal microflora in predicting the progression of Hepatitis B patients in different non-cancerous stages.

Results
A total of 266 patients with different stages of Hepatitis B and 31 healthy controls were included in this study. Some of the subjects (217 cases) underwent 16S rRNA gene sequencing. Compared with the control group (CK), the α diversity of patients in Group A (HBV carrier) slightly increased, while that of patients in the other three groups decreased. Each group of patients, especially those in Group C (cirrhosis) and Group D (acute-on-chronic liver failure), could be separated from the CK using weighted UniFrac PCoA and ANOSIM. LEfSe revealed that 40 taxa belonging to three phyla had an LDA larger than 4. In addition to the comparison between Group B (chronic Hepatitis B) and Group C, the specific flora and potential taxonomic function were also identified. Different microbial communities were found to be highly correlated with clinical indicators and the Child-Pugh scores. Changes in the microbial community were highly related to the alternations of host metabolism, which in turn, was related to the development of Hepatitis B. Our analysis identified a total of 47 strains with potential biomarker functions at all levels except for the phylum level.

Conclusions
Faecal microbiota transplantation of some potential beneficial bacteria can change with the occurrence of disease, and HBV carriers might be the most suitable donors.
Treating primary immunodeficiencies with defects in NK cells: from stem cell therapy to gene editing
Authors: Eguizabal C. , Herrera L. , Inglés-Ferrándiz M. , Izpisua Belmonte J. C. 
Published: October 2020

AbstractPrimary immunodeficiency diseases (PIDs) are rare diseases that are characterized by genetic mutations that damage immunological function, defense, or both. Some of these rare diseases are caused by aberrations in the normal development of natural killer cells (NKs) or affect their lytic synapse. The pathogenesis of these types of diseases as well as the processes underlying target recognition by human NK cells is not well understood. Utilizing induced pluripotent stem cells (iPSCs) will aid in the study of human disorders, especially in the PIDs with defects in NK cells for PID disease modeling. This, together with genome editing technology, makes it possible for us to facilitate the discovery of future therapeutics and/or cell therapy treatments for these patients, because, to date, the only curative treatment available in the most severe cases is hematopoietic stem cell transplantation (HSCT). Recent progress in gene editing technology using CRISPR/Cas9 has significantly increased our capability to precisely modify target sites in the human genome. Among the many tools available for us to study human PIDs, disease- and patient-specific iPSCs together with gene editing offer unique and exceptional methodologies to gain deeper and more thorough understanding of these diseases as well as develop possible alternative treatment strategies. In this review, we will discuss some immunodeficiency disorders affecting NK cell function, such as classical NK deficiencies (CNKD), functional NK deficiencies (FNKD), and PIDs with involving NK cells as well as strategies to model and correct these diseases for further study and possible avenues for future therapies.
RNA-seq reveals tight junction-relevant erythropoietic fate induced by OCT4 in human hair follicle mesenchymal stem cells
Authors: Yu Xiaozhen , Sun Pengpeng , Huang Xingang , Chen Hua , Huang Weiqing , Ruan Yingchun , Jiang Weina , Tan Xiaohua , Liu Zhijing 
Published: October 2020

Abstract
Background
Human hair follicle mesenchymal stem cells (hHFMSCs) isolated from hair follicles possess multilineage differentiation potential. OCT4 is a gene critically associated with pluripotency properties. The cell morphology and adhesion of hHFMSCs significantly changed after transduction of OCT4 and two subpopulations emerged, including adherent cells and floating cell. Floating cells cultured in hematopoietic induction medium and stimulated with erythropoetic growth factors could transdifferentiate into mature erythrocytes, whereas adherent cells formed negligible hematopoietic colonies. The aim of this study was to reveal the role of cell morphology and adhesion on erythropoiesis induced by OCT4 in hHFMSCs and to characterize the molecular mechanisms involved.

Methods
Floating cell was separated from adherent cell by centrifugation of the upper medium during cell culture. Cell size was observed through flow cytometry and cell adhesion was tested by disassociation and adhesion assays. RNA sequencing was performed to detect genome-wide transcriptomes and identify differentially expressed genes. GO enrichment analysis and KEGG pathway analysis were performed to analysis the functions and pathways enriched by differentially expressed genes. The expression of tight junction core members was verified by qPCR and Western blot. A regulatory network was constructed to figure out the relationship between cell adhesin, cytoskeleton, pluripotency, and hematopoiesis.

Results
The overexpression of OCT4 influenced the morphology and adhesion of hHFMSCs. Transcripts in floating cells and adherent cells are quite different. Data analysis showed that upregulated genes in floating cells were mainly related to pluripotency, germ layer development (including hematopoiesis lineage development), and downregulated genes were mainly related to cell adhesion, cell junctions, and the cytoskeleton. Most molecules of the tight junction (TJ) pathway were downregulated and molecular homeostasis of the TJ was disturbed, as CLDNs were disrupted, and JAMs and TJPs were upregulated. The dynamic expression of cell adhesion-related gene E-cadherin and cytoskeleton-related gene ACTN2 might cause different morphology and adhesion. Finally, a regulatory network centered to OCT4 was constructed, which elucidated that he TJ pathway critically bridges pluripotency and hematopoiesis in a TJP1-dependent way.

Conclusions
Regulations of cell morphology and adhesion via the TJ pathway conducted by OCT4 might modulate hematopoiesis in hHFMSCs, thus developing potential mechanism of erythropoiesis in vitro.
Chemoinformatics-based enumeration of chemical libraries: a tutorial
Authors: Saldívar-González Fernanda I. , Huerta-García C. Sebastian , Medina-Franco José L. 
Published: October 2020

AbstractVirtual compound libraries are increasingly being used in computer-assisted drug discovery applications and have led to numerous successful cases. This paper aims to examine the fundamental concepts of library design and describe how to enumerate virtual libraries using open source tools. To exemplify the enumeration of chemical libraries, we emphasize the use of pre-validated or reported reactions and accessible chemical reagents. This tutorial shows a step-by-step procedure for anyone interested in designing and building chemical libraries with or without chemoinformatics experience. The aim is to explore various methodologies proposed by synthetic organic chemists and explore affordable chemical space using open-access chemoinformatics tools. As part of the tutorial, we discuss three examples of design: a Diversity-Oriented-Synthesis library based on lactams, a bis-heterocyclic combinatorial library, and a set of target-oriented molecules: isoindolinone based compounds as potential acetylcholinesterase inhibitors. This manuscript also seeks to contribute to the critical task of teaching and learning chemoinformatics.