bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors Associated With Loss-To-Follow-Up Of Hiv-Positive Mothers And Their Infants Enrolled In Hiv Care Clinic: A Qualitative Study
Authors: Mpinganjira Samuel Lawrent , Tchereni Timothy , Gunda Andrews , Mwapasa Victor 
Published: February 2020

Abstract
Background
In Malawi, loss to follow-up (LTFU) of HIV-positive pregnant and postpartum women on Option B+ regimen greatly contributes to sub-optimal retention, estimated to be 74% at 12 months postpartum. This threatens Malawi’s efforts to eliminate mother-to-child transmission of HIV. We investigated factors associated with LTFU among Mother-Infant Pairs.
Methods
We conducted a qualitative study, nested within the “Promoting Retention Among Infants and Mothers Effectively (PRIME)” study, a 3-arm cluster randomized trial assessing the effectiveness of strategies for improving retention of mother-infant pairs in HIV care in Salima and Mangochi districts, Malawi. From July to December 2016, we traced and interviewed 19 LTFU women. In addition, we interviewed 30 healthcare workers from health facilities where the LTFU women were receiving care. Recorded interviews were transcribed, translated and then analysed using deductive content analysis.
Results
The following reasons were reported as contributing to LTFU: lack of support from husbands or family members; long distance to health facilities; poverty; community-level stigma; ART side effects; perceived good health after taking ART and adoption of other alternative HIV treatment options.
Conclusion
Our study has found multiple factors at personal, family, community and health system levels, which contribute to poor retention of mother-infant pairs in HIV care.
Key words
PRIME, PMTCT, loss to follow up, mother-infant pairs, retention, Option B+
Percutaneous Coronary Intervention in Diabetic versus Non-diabetic Patients with Prior Coronary Artery Bypass Grafting: A Propensity Score Matching Study
Authors: Ma Xiaolong , Dong Ran , Chen Pengfei , Zhao Yichen , Zeng Caiwu , Xin Meng , Ye Qing , Wang Jiangang 
Published: February 2020

Abstract
Background: The target of this study was to explore the outcomes of percutaneous coronary intervention (PCI) in diabetic versus non-diabetic patients with prior coronary artery bypass grafting (CABG) surgery.
Methods: Seven hundred and twenty four patients who had previously received CABG and had been treated using PCI combined with drug-eluting stents (DES) between 2009 and 2017 were selected for a retrospective study and allocated into either a diabetes mellitus (DM) or non-diabetes mellitus (No DM) group. A 1:1 propensity score-matched evaluation was conducted and risk adjusted for analysis. The primary outcomes were cardiac death, myocardial infarction, heart failure and revascularization, with a median follow-up duration of 5.13 years.
Results: After matching, two-, 5- and 8-year event rate of overall major adverse cardiac events (MACEs) were found to be higher in the DM group (No DM vs DM:15.3%, 30.9%, 38.5% vs 19.8%, 37.8%, 52.2%, respectively), although no significant difference was found in the event rate of overall MACEs (hazard ratio [HR]: 1.35; 95% confidence interval [CI]: 1.00 to 1.83 for DM vs No DM; P=0.052), cardiac death (HR: 0.94; 95% CI: 0.45 to 1.95; P=0.871), MI (HR: 1.49; 95% CI: 0.95 to 2.32; P=0.080), HF (HR: 1.54; 95% CI: 0.90 to 2.63 for; P=0.120) or revascularization (HR: 1.07; 95% CI: 0.72 to 1.59; P=0.747). Subgroup analysis of PCI in only the NCA showed MACEs (adjusted HR: 1.13; 95% CI: 0.85 to 1.49 for DM vs No DM; P=0.325), cardiac death (adjusted HR: 0.85; 95% CI: 0.41 to 1.78 for DM vs No DM; P=0.781), MI (adjusted HR: 1.32; 95% CI: 0.84 to 2.01 for DM vs No DM; P=0.069), HF (adjusted HR: 1.41; 95% CI: 0.87 to 2.27 for DM vs No DM; P=0.211) or repeated revascularization (adjusted HR: 0.93; 95% CI: 0.64 to 1.37 for DM vs No DM; P=0.836).
Conclusions : Compared with non-diabetic patients with prior CABG, subsequent implantation of DES in the native coronary artery of diabetic patients resulted in apparently similar outcomes.
Trial registration : This study was not registered in an open access database.
Key Words: Percutaneous coronary intervention; Diabetic; Non-diabetic; Coronary artery bypass grafting.
Active Ankylosing Spondylitis Increases Blood Loss during Total Hip Arthroplasty for a Stiff Hip Joint
Authors: Hu Yong , Jiang Wei-Zhou , Pan Cheng-Long , Wang Tao 
Published: February 2020

Abstract
Background: Total hip arthroplasty (THA) has been highlighted as the best treatment option for ankylosing spondylitis (AS) patients with advanced hip involvement. The huge blood loss associated with THA is a common concern of postoperative complications. Disease activity is a specific reflection of systematic inflammation of AS. The purpose of this study was to determine the eﬀect of disease activity on blood loss during THA in patients with AS. Methods: Forty-nine patients with AS who underwent unilateral THAs were retrospectively studied. Ankylosing Spondylitis Disease Activity Score (ASDAS) was employed to evaluate the disease activity. Orthopedic Surgery Transfusion Hemoglobin European Overview (OSTHEO) formula was used to assess the surgical blood loss. The patients were divided into active group (ASDAS≥1.3; n=32) and stable groups (ASDAS<1.3; n=17) based on the ASDAS. Peri-operative laboratory values, plain radiographs, intra-operative data, transfusion volume, and use of hemostatic agents were recorded and statistically analyzed. Results: The ASDAS, pre-operative C-reactive protein level, erythrocyte sedimentation rate, and fibrinogen concentration in the active group were higher than the stable group (all P<0.05); however, the pre-operative hemoglobin concentration and albumin level were higher in the stable group (both P<0.05). The total blood loss during THA in stable patients was 1415.31 mL and 2035.04 mL in active patients (P=0.006). The difference between the two groups was shown to be consistent after excluding the gender difference (P=0.030). A high transfusion rate existed in both groups (stable group, 76.47% with an average of 1.53 units; active group, 84.37% with an average of 2.31 units), but there was no significant difference between the two groups (both P >0.05). Compensated blood loss, corresponding to transfusion, was noted significantly more in the active group compared to the stable group (P=0.027). There was no significant difference with regard to functional recovery (P>0.05). Conclusion: Active AS patients are at high risk for increased blood loss during THA compared to stable patients. The underlying mechanism includes disorders of the coagulation and fibrinolytic systems, poor nutrition status, osteoporosis, imbalance of oxidative–antioxidative status and local inflammatory reaction. It is strongly recommended to perform THA in AS patients with stable disease.
Tumour suppressor OTUD3 induces growth inhibition and apoptosis by directly deubiquitinating and stabilizing p53 in invasive breast carcinoma cells
Authors: Pu Qian , Lv Yan-Rong , Dong Ke , Geng Wen-Wen , Gao Hai-Dong 
Published: February 2020

Abstract
Background P53 pathway inactivation plays an important role in the process of breast cancer tumourigenesis. Post-translational protein modification abnormalities have been confirmed to be an important mechanism underlying the inactivation of p53. Numerous deubiquitinating enzymes are aberrantly expressed in breast cancer, and a few deubiquitination enzymes are capable of deubiquitinating and stabilizing p53. Here, we report that OTUD3 is a deubiquitylase of p53 in breast carcinoma. Methods The correlation between the mRNA expression of OTUD3, TP53 and PTEN and the prognosis of BC was assessed with the Kaplan-Meier Plotter tool. OTUD3 protein expression in breast carcinoma was examined by immunohistochemistry and western blotting. The relationship among OTUD3, p53, and p21 proteins was analysed. Half-life analysis and ubiquitylation assay were performed to elucidate the molecular mechanism by which OTUD3 stabilizes p53. The interaction between OTUD3 and p53 in BC cells was verified by a co-immunoprecipitation assay and GST pulldown experiments. MTS proliferation detection, an apoptosis detection kit and colony formation asssy were used to investigate the functional effects of OTUD3 on breast cancer cells. Results OTUD3 downregulation is correlated with a poor prognosis in BC patients. OTUD3 expression is decreased in breast cancer tissues and independent of the histological grade.OTUD3 also inhibits cell proliferation and clone formation and increases the sensitivity of BC cells to apoptosis induced by chemotherapy drugs. A reduction in OTUD3 expression concomitant with decreased p53 abundance is correlated with human breast cancer progression. The ectopic expression of wild-type OTUD3, but not its catalytically inactive mutant, stabilizes and activates p53. Mechanistically, OTUD3 interacts directly with p53 through the amino-terminal OTU region. Finally, OTUD3 protects p53 from Mdm2-mediated ubiquitination and degradation, enabling the deubiquitination of p53 in BC cells. Conclusions In summary, we establish that OTUD3 is a potential therapeutic target for restoring p53 function in breast cancer cells and suggest that the OTUD3-p53 signalling axis plays a critical role in tumour suppression.
A comparison of erythrocyte sedimentation rates of bloods anticoagulated with trisodium citrate and EDTA among TB presumptive patients at the University of Gondar comprehensive specialized hospital, northwest Ethiopia
Authors: Getaneh Zegeye , Ayelgn Fekadu , Asemahegn Geletaw , Geleta Habtamu , Yalew Aregawi , Melak Tadele 
Published: February 2020

Abstract
Objective: The purpose of this study was comparing the erythrocyte sedimentation rate (ESR) results of trisodium citrate (TSC) and ethylene diamine tetra-acetic acid (EDTA) anticoagulants. A comparative cross-sectional study was conducted at the University of Gondar specialized referral hospital, northwest, Ethiopia. A total of 70 TB presumptive participants were recruited. From each of the 70 participants of the study, 3 and 1.6 ml of blood was collected in EDTA tubes and 0.4 ml of trisodium Citrate anticoagulant containing test tubes, respectively.
Results: The mean ± SD values of ESR were 57.9 ± 41.45 mm/hr in EDTA and 50.99 ± 43.5 mm/hr in TSC anticoagulated blood. The mean difference of ESR values between EDTA and TSC blood (6.91 ± 13.66 mm/hr) was statistically significant. The Mean ± SD of ESR values using EDTA and TSC in males were 59.57 ± 42.31 and 53.57 ± 44.61 mm/hr while for females it was 54.71±40.44 and 46.04 ± 41.82 mm/hr, respectively. The study indicated that there was a significant difference between ESR values with EDTA and tri-sodium citrate anticoagulants.

Keywords: Erythrocyte sedimentation rate, EDTA, Tri-sodium citrate, Westergren Method, Comparison
A recurrent ABCC2 p.G693R mutation resulting in loss of function of MRP2 and hyperbilirubinemia in Dubin-Johnson syndrome in China
Authors: Wu Lina , Li Yanmeng , Song Yi , Zhou Donghu , Jia Siyu , Xu Anjian , Zhang Wei , You Hong , Jia Jidong , Huang Jian , Ou Xiaojuan 
Published: February 2020

Abstract
Background: Dubin-Johnson syndrome (DJS) is a rare autosomal recessive disorder characterized by predominantly conjugated hyperbilirubinemia that is caused by pathogenic mutations in the adenosine triphosphate-binding cassette subfamily C member 2 ( ABCC2 ) gene, which encodes multidrug resistance-associated protein 2 (MRP2). However, little is known about the causative mutation of DJS in China. Recently, we have reported ABCC2 p.G693R mutation in two unrelated cases. In the present study, we investigated the pathogenicity of the ABCC2 p.G693R mutation in DJS in China. Methods: Clinical and genetic analysis was conducted for the two patients with the ABCC2 p.G693R mutation. Whole exome sequencing for mutations in other known hyperbilirubinemia-related genes was conducted for the cases with ABCC2 p.G693R. Expression and cellular localization of the mutant MRP2 p.G693R were analyzed by Western blotting and immunofluorescence assay, respectively. Organic anion transport activity was evaluated by the analysis of glutathione-conjugated-monochlorobimane. Results: The two DJS patients with ABCC2 p.G693R mutation, which was conserved among different species, showed typical hyperbilirubinemia phenotype. No pathogenic mutation was identified in the other known hyperbilirubinemia related genes. Functional studies in three cell lines showed that the expression, localization and the organic anion transport activity were significantly compromised by MRP2 p.G693R mutation compared with wild-type MRP2. Conclusions: The recurrent ABCC2 p.G693R mutation is associated with loss of function of the MRP2 protein and may result in hyperbilirubinemia in DJS in China.
Identification of Four Novel Mutations in Chilean Patients with Various Forms of Maple Syrup Urine Disease&nbsp;
Authors: Campanholi Diana Ruffato Resende , Margutti Ana Vitoria Barban , Silva Wilson Araújo , Garcia Daniel Fantozzi , Molfetta Greice Andreotti de , Marques Adriana Aparecida , Schwartz Ida Vanessa Döederlein , Cornejo Veronica , Hamilton Valerie , Castro Gabriela , Borges Ester Simon , Junior José Simon Camelo 
Published: February 2020

Abstract

Background: Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disorder caused by the deficient activity of the branched-chain α-keto acid dehydrogenase (BCKD) enzymatic complex. BCKD is a mitochondrial complex encoded by four genes: BCKDHA, BCKDHB, DBT, and DLD. MSUD is predominantly caused by mutations in the BCKDHA, BCKDHB, and DBT genes which encode the E1α, E1β, and E2 subunits of the BCKD complex, respectively. The aim of this study was to characterize the genetic basis of MSUD in a cohort of Chilean MSUD patients by identifying point mutations in the BCKDHA, BCKDHB, and DBT genes and to describe their impact on the phenotypic heterogeneity of these patients. This manuscript describes a cross-sectional study of 18 MSUD patients carried out using PCR and DNA sequencing.Results: Four novel pathogenic mutations were identified: one in BCKDHA (p.Thr338Ile), two in BCKDHB (p.Gly336Ser e p.Pro240Thr), and one in DBT (p.Gly406Asp). Four additional pathogenic mutations found in this study have been described previously.Conclusion: There were no correlations between the genotype and phenotype of the patients. Thus, if MSUD is diagnosed earlier, with a neonatal screening approach, it might be possible to establish genotype-phenotype relationships more efficiently.
Intentional Carbofuran Poisoning in 7 dogs
Authors: Pivariu Dalma , Oros Adrian Nechita , Tabaran Flaviu , Gal Adrian , Martonos Cristian , Nagy Andras Laszlo 
Published: February 2020

Abstract
Background: Carbofuran was a widely used board-spectrum pesticide, which despite his strict regulation and bans for more than one decade is still encountered in cases of intentional poisoning in dogs and wildlife. The objective of the study was to provide a complete and detailed description of the pathological, histological and toxicological findings of the 7 cases of intentional carbofuran poisoning in dogs. Results: In this retrospective study 7 cases of carbofuran intoxication recorded from July 2015 to June 2017 were analyzed. Following complete history recording, all cases were examined by complete necropsy and histopathology. The carbofuran intoxication was confirmed in all cases by gas-chromatography. The postmortem examination revealed extensive haemorrhages and congestion located mainly within the respiratory, nervous and cardiovascular systems, accompanied by degeneration and necrosis within the lung, heart, and kidneys. Conclusions: Although banned in the European Union, carbamate poisoning is still frequently encountered, especially in wild animals. This paper will contribute to a better understanding of occurrence and pathogenesis of acute carbofuran exposure in dogs, and add some peculiar pathological features of this poisoning to current literature.
Fusion transcript detection using spatial transcriptomics
Authors: Friedrich Stefanie , Sonnhammer Erik LL 
Published: February 2020

Abstract
Background
Fusion transcripts are involved in tumourigenesis and play a crucial role in tumour heterogeneity, tumour evolution and cancer treatment resistance. However, fusion transcripts have not been studied at high spatial resolution in tissue sections due to the lack of full-length transcripts with spatial information. New high-throughput technologies like spatial transcriptomics measure the transcriptome of tissue sections on almost single-cell level. While this technique does not allow for direct detection of fusion transcripts, we show that they can be inferred using the relative poly(A) tail abundance of the involved parental genes.

Method
We present a new method STfusion, which uses spatial transcriptomics to infer the presence and absence of poly(A) tails. A fusion transcript lacks a poly(A) tail for the 5´ gene and has an elevated number of poly(A) tails for the 3´ gene. Its expression level is defined by the upstream promoter of the 5´ gene. STfusion measures the difference between the observed and expected number of poly(A) tails with a novel C-score.

Results
We verified the STfusion ability to predict fusion transcripts on HeLa cells with known fusions. STfusion and C-score applied to clinical prostate cancer data revealed the spatial distribution of the cis-SAGe SLC45A3-ELK4 in 12 tissue sections with almost single-cell resolution. The cis-SAGe occurred in disease areas, e.g. inflamed, prostatic intraepithelial neoplastic, or cancerous areas, and occasionally in normal glands.

Conclusions
STfusion detects fusion transcripts in cancer cell line and clinical tissue data, and distinguishes chimeric transcripts from chimeras caused by trans-splicing events. With STfusion and the use of C-scores, fusion transcripts can be spatially localised in clinical tissue sections on almost single cell level.

Keywords
Fusion transcript detection, Spatial Transcriptomics, gene fusion, cis-SAGE, oncogene
Development of Leishmania (Mundinia) in guinea pigs
Authors: Bečvář Tomáš , Siriyasatien Padet , Bates Paul , Volf Petr , Sádlová Jovana 
Published: February 2020

Abstract
Background: Leishmaniasis is a human and animal disease caused by parasites of the genus Leishmania, which is now divided into 4 subgenera – L. (Leishmania), L. (Viannia), L. (Sauroleishmania) and L. (Mundinia). Subgenus Mundinia, established in 2016, is geographically widely dispersed, its distribution covers all continents, except Antarctica. It consists of 5 species - L. enriettii and L. macropodum are parasites of wild mammals while L. martiniquensis, L. orientalis and unnamed L. sp. from Ghana are infectious to humans. There is very little information on natural reservoir hosts and vectors for any Mundinia species. Methods: Experimental infections of guinea-pigs with all five Mundinia species were performed. Animals were injected intradermally with 107 culture-derived promastigotes into both ear pinnae. The courses of infections were monitored weekly; xenodiagnoses were performed at weeks 4 and 8 post infection using Lutzomyia migonei. The distribution of parasites in different tissues was determined post mortem by conventional PCR.Results: No significant differences in weight were observed between infected animals and the control group. Animals infected with L. enriettii developed temporary lesions at the site of inoculation and were infectious to Lu. migonei in xenodiagnoses. Animals infected with L. martiniquensis and L. orientalis developed temporary erythema and dry lesions at the site of inoculation, respectively, but were not infectious to sand flies. Guinea pigs infected by L. macropodum and L. sp. from Ghana showed no signs of infection during experiments, were not infectious to sand flies and leishmanial DNA was not detected in their tissue samples at the end of experiments at week 12 post-inoculation.Conclusions: According to our results, guinea pigs are not an appropriate model organism for studying Mundinia species other than L. enriettii. We suggest that for better understanding of L. (Mundinia) biology it is necessary to focus on other model organisms.
Pleiotropic effect of the ABCG2 gene in gout: involvement in serum urate levels and progression from hyperuricemia to gout
Authors: Wrigley Rebekah , Phipps-Green Amanda J , Topless Ruth K , Major Tanya J , Cadzow Murray , Riches Philip , Tausche Anne-Kathrin , Janssen Matthijs , Joosten Leo AB , Jansen Tim L , So Alexander , Hindmarsh Jennie Harré , Stamp Lisa K , Dalbeth Nicola , Merriman Tony 
Published: February 2020

Abstract
Background

The ABCG2 Q141K ( rs2231142 ) and rs10011796 variants associate with hyperuricaemia (HU). The effect size of ABCG2 rs2231142 on urate is ~60% that of SLC2A9, yet the effect size on gout is greater. We tested the hypothesis that ABCG2 plays a role in the progression from HU to gout by testing for association of ABCG2 rs2231142 and rs10011796 with gout using HU controls.

Methods

We analysed 1,699 European gout cases and 14,350 normourciemic (NU) and HU controls, and 912 New Zealand (NZ) Polynesian (divided into Eastern and Western Polynesian) gout cases and 696 controls. Association testing was performed using logistic and linear regression with multivariate adjusting for confounding variables.

Results

In Europeans and Polynesians, the ABCG2 141K (T) allele was associated with gout using HU controls (OR=1.85, P =3.8E -21 and OR meta =1.85, P =1.3E -03 , respectively). There was evidence for an effect of 141K in determining HU in European (OR=1.56, P =1.7E -18 ) but not in Polynesian (OR meta =1.49, P =0.057). For SLC2A9 rs11942223, the T allele associated with gout in the presence of HU in European (OR=1.37, P =4.7E -06 ), however significantly weaker than ABCG2 rs2231142 141K ( P Het =0.0023). In Western Polynesian and European, there was epistatic interaction between ABCG2 rs2231142 and rs10011796 . Combining the presence of the 141K allele with the rs10011796 CC-genotype increased gout risk, in the presence of HU, 21.5-fold in Western Polynesian ( P =0.009) and 2.6-fold in European ( P =9.9E -06 ). The 141K allele of ABCG2 associated with increased gout flare frequency in Polynesian ( P meta = 2.5E -03 ).

Conclusion

These data are consistent with a role for ABCG2 141K in gout in the presence of established HU.