bluuebunny/crossref_metadata_2025_split huggingface dataset:
Islet-expressed circular RNAs are associated with type 2 diabetes status in human primary islets and in peripheral blood
Authors: Haque Shahnaz , Ames Ryan M. , Moore Karen , Lee Benjamin P. , Jeffery Nicola , Harries Lorna W. 
Published: April 2020

Abstract
Background
Circular RNAs are non-coding RNA molecules with gene regulatory potential that have been associated with several human diseases. They are stable and present in the circulation, making them excellent candidates for biomarkers of disease. Despite their promise as biomarkers or future therapeutic targets, information on their expression and functionality in human pancreatic islets is a relatively unexplored subject.

Methods
Here we aimed to produce an enriched circRNAome profile for human pancreatic islets by CircleSeq, and to explore the relationship between circRNA expression, diabetes status, genotype at T2D risk loci and measures of glycaemia (insulin secretory index; SI and HbA1c) in human islet preparations from healthy control donors and donors with type 2 diabetes using ANOVA or linear regression as appropriate. We also assessed the effect of elevated glucose, cytokine and lipid and hypoxia on circRNA expression in the human beta cell line EndoC-βH1.

Results
We identified over 2600 circRNAs present in human islets. Of the five most abundant circRNAs in human islets, four (circCIRBP, circZKSCAN, circRPH3AL and circCAMSAP1) demonstrated marked associations with diabetes status. CircCIRBP demonstrated an association with insulin secretory index in isolated human islets and circCIRBP and circRPH3AL displayed altered expression with elevated fatty acid in treated EndoC-βH1 cells. CircCAMSAP1 was also noted to be associated with T2D status in human peripheral blood. No associations between circRNA expression and genotype at T2D risk loci were identified in our samples.

Conclusions
Our data suggest that circRNAs are abundantly expressed in human islets, and that some are differentially regulated in the islets of donors with type 2 diabetes. Some islet circRNAs are also expressed in peripheral blood and the expression of one, circCAMSAP1, correlates with diabetes status. These findings highlight the potential of circRNAs as biomarkers for T2D.
Long-term expansion of directly reprogrammed keratinocyte-like cells and in vitro reconstitution of human skin
Authors: Zheng Jie , Yun Wonjin , Park Junghyun , Kang Phil Jun , Lee Gilju , Song Gwonhwa , Kim In Yong , You Seungkwon 
Published: April 2020

AbstractBackgroundHuman keratinocytes and derived products are crucial for skin repair and regeneration. Despite substantial advances in engineered skin equivalents, their poor availability and immunorejection remain major challenges in skin grafting.MethodsInduced keratinocyte-like cells (iKCs) were directly reprogrammed from human urine cells by retroviral transduction of two lineage-specific transcription factors BMI1 and △NP63α (BN). Expression of keratinocyte stem cell or their differentiation markers were assessed by PCR, immunofluorescence and RNA-Sequencing. Regeneration capacity of iKCs were assessed by reconstitution of a human skin equivalent under air-interface condition.ResultsBN-driven iKCs were similar to primary keratinocytes (pKCs) in terms of their morphology, protein expression, differentiation potential, and global gene expression. Moreover, BN-iKCs self-assembled to form stratified skin equivalents in vitro.ConclusionsThis study demonstrated an approach to generate human iKCs that could be directly reprogrammed from human somatic cells and extensively expanded in serum- and feeder cell-free systems, which will facilitate their broad applicability in an efficient and patient-specific manner.
Distance sampling for epidemiology: an interactive tool for estimating under-reporting of cases from clinic data
Authors: Nelli Luca , Guelbeogo Moussa , Ferguson Heather M. , Ouattara Daouda , Tiono Alfred , N’Fale Sagnon , Matthiopoulos Jason 
Published: April 2020

AbstractBackgroundDistance sampling methods are widely used in ecology to estimate and map the abundance of animal and plant populations from spatial survey data. The key underlying concept in distance sampling is the detection function, the probability of detecting the occurrence of an event as a function of its distance from the observer, as well as other covariates that may influence detection. In epidemiology, the burden and distribution of infectious disease is often inferred from cases that are reported at clinics and hospitals. In areas with few public health facilities and low accessibility, the probability of detecting a case is also a function of the distance between an infected person and the “observer” (e.g. a health centre). While the problem of distance-related under-reporting is acknowledged in public health; there are few quantitative methods for assessing and correcting for this bias when mapping disease incidence. Here, we develop a modified version of distance sampling for prediction of infectious disease incidence by relaxing some of the framework’s fundamental assumptions. We illustrate the utility of this approach using as our example malaria distribution in rural Burkina Faso, where there is a large population at risk but relatively low accessibility of health facilities.ResultsThe modified distance-sampling framework was used to predict the probability of reporting malaria infection at 8 rural clinics, based on road-travel distances from villages. The rate at which reporting probability dropped with distance varied between clinics, depending on road and clinic positions. The probability of case detection was estimated as 0.3–1 in the immediate vicinity of the clinic, dropping to 0.1–0.6 at a travel distance of 10 km, and effectively zero at distances > 30–40 km.ConclusionsTo enhance the method’s strategic impact, we provide an interactive mapping tool (as a self-contained R Shiny app) that can be used by non-specialists to interrogate model outputs and visualize how the overall probability of under-reporting and the catchment area of each clinic is influenced by changing the number and spatial allocation of health centres.
Protection of the transplant kidney during cold perfusion with doxycycline: proteomic analysis in a rat model
Authors: Moser Michael A. J. , Sawicka Katherine , Sawicka Jolanta , Franczak Aleksandra , Cohen Alejandro , Bil-Lula Iwona , Sawicki Grzegorz 
Published: April 2020

Abstract
Background
It has been previously shown that doxycycline (Doxy) protects the kidney from preservation injury by inhibition of matrix metalloproteinase. However, the precise molecular mechanism involved in this protection from injury is not known. We used a pharmaco-proteomics approach to identify potential molecular targets associated with kidney preservation injury.

Methods
Rat kidneys were cold perfused with or without doxycycline (Doxy) for 22 h. Kidneys perfusates were analyzed for the presence of injury markers such as lactate dehydrogenase (LDH), and neutrophil-gelatinase associated lipocalin (NGAL). Proteins extracted from kidney tissue were analyzed by 2-dimensional gel electrophoresis. Proteins of interest were identified by mass spectrometry.

Results
Triosephosphate isomerase, PGM, dihydropteridine reductase-2, pyridine nucleotide-disulfide oxidoreductase, phosphotriesterase-related protein, and aminoacylase-1A were not affected by cold perfusion. Perfusion with Doxy increased their levels. N(G),N(G)-dimethylarginine dimethylaminohydrolase and phosphoglycerate kinase 1 were decreased after cold perfusion. Perfusion with Doxy led to an increase in their levels.

Conclusions
This study revealed specific metabolic enzymes involved in preservation injury and in the mechanism whereby Doxy protects the kidney against injury during cold perfusion.
Clinical analysis of ultrasound-guided radiofrequency ablation for recurrent colorectal liver metastases after hepatectomy
Authors: Fan Xiao-xiang , Lv Shu-yi , Zhang Mei-wu , Dai Xiao-yu , Zhao Jian-pei , Mao Da-feng , Zhang Yan 
Published: April 2020

Abstract
Background
RFA is designed to produce localized tumor destruction by heating the tumor and surrounding liver tissue, especially suitable for patients who do not qualify for hepatic resection. Many studies have reported that RFA was inferior to hepatectomy in the treatment of recurrent colorectal liver metastases. However, strong evidence is lacking in the literature. This study aimed to investigate the effect and clinical outcome of percutaneous ultrasound-guided RFA and repeat hepatic resection for recurrent colorectal liver metastases after hepatectomy.

Methods
From January 2007 to January 2014, 194 patients with recurrent colorectal liver metastases after hepatectomy diagnosed in our hospital was performed, and then divided into two groups based on different regimens: repeat hepatic resection group and RFA group. The clinical data of the two groups were analyzed. After treatment, the liver function-related indexes, complication rate, survival rate, and tumor recurrence of the two groups were recorded. The difference in short-term and long-term effects between repeat hepatic resection and RFA was identified by propensity score analysis.

Results
The number of metastases and the proportion of left and right lobe involved by tumor and preoperative chemotherapy in the RFA group were higher than those in the repeat hepatic resection group. The clinical data showed no significant difference between the two groups after using propensity score analysis. Compared with the RFA group, the liver function of the repeat hepatic resection group was significantly improved. After adjustment for potential confounders, no significant difference in liver function-related indexes was found between RFA and repeat hepatic resection, and the incidence of complications in the RFA group was lower. In survival analysis, there was no significant difference in OS and DFS between the two groups.

Conclusions
RFA is a safe and effective therapeutic option for patients with recurrent colorectal liver metastases after hepatectomy.
Hi-D: nanoscale mapping of nuclear dynamics in single living cells
Authors: Shaban Haitham A. , Barth Roman , Recoules Ludmila , Bystricky Kerstin 
Published: April 2020

AbstractBulk chromatin motion has not been analyzed at high resolution. We present Hi-D, a method to quantitatively map dynamics of chromatin and abundant nuclear proteins for every pixel simultaneously over the entire nucleus from fluorescence image series. Hi-D combines reconstruction of chromatin motion and classification of local diffusion processes by Bayesian inference. We show that DNA dynamics in the nuclear interior are spatially partitioned into 0.3–3-μm domains in a mosaic-like pattern, uncoupled from chromatin compaction. This pattern was remodeled in response to transcriptional activity. Hi-D can be applied to any dense and bulk structures opening new perspectives towards understanding motion of nuclear molecules.
Serial prophylactic exchange blood transfusion in pregnant women with sickle cell disease (TAPS-2): study protocol for a randomised controlled feasibility trial
Authors: Oakley Laura L. , Awogbade Moji , Brien Sarah , Briley Annette , Chorozoglou Maria , Drasar Emma , Johns Jemma , Rhodes Elizabeth , Robinson Vicky , Seed Paul , Sharif Joseph , Singh Claire , Telfer Paul , Thompson Hilary , Watt-Coote Ingrid , Howard Jo , Oteng-Ntim Eugene 
Published: April 2020

Abstract
Background
Pregnancies in women with sickle cell disease (SCD) are associated with a higher risk of sickle and pregnancy complications. Limited options exist for treating SCD during pregnancy. Serial prophylactic exchange blood transfusion (SPEBT) has been shown to be effective in treating SCD outside pregnancy, but evidence is lacking regarding its use during pregnancy. The aim of this study is to assess the feasibility and acceptability of conducting a future phase 3 randomised controlled trial (RCT) to establish the clinical and cost effectiveness of SPEBT in pregnant women with SCD.

Methods
The study is an individually randomised, two-arm, feasibility trial with embedded qualitative and health economic studies. Fifty women, 18 years of age and older, with SCD and a singleton pregnancy at ≤ 18 weeks’ gestation will be recruited from six hospitals in England. Randomisation will be conducted using a secure online database and minimised by centre, SCD genotype and maternal age. Women allocated to the intervention arm will receive SPEBT commencing at ≤ 18 weeks’ gestation, performed using automated erythrocytapheresis every 6–10 weeks until the end of pregnancy, aiming to maintain HbS% or combined HbS/HbC% below 30%. Women in the standard care arm will only receive transfusion when clinically indicated. The primary outcome will be the recruitment rate. Additional endpoints include reasons for refusal to participate, attrition rate, protocol adherence, and maternal and neonatal outcomes. Women will be monitored throughout pregnancy to assess maternal, sickle, and foetal complications. Detailed information about adverse events (including hospital admission) and birth outcomes will be extracted from medical records and via interview at 6 weeks postpartum. An embedded qualitative study will consist of interviews with (a) 15–25 trial participants to assess experiences and acceptability, (b) 5–15 women who decline to participate to identify barriers to recruitment and (c) 15–20 clinical staff to explore fidelity and acceptability. A health economic study will inform a future cost effectiveness and cost-utility analysis.

Discussion
This feasibility study aims to rigorously evaluate SPEBT as a treatment for SCD in pregnancy and its impact on maternal and infant outcomes.

Trial registration
NIH registry (www.clinicaltrials.gov), registration number NCT03975894 (registered 05/06/19); ISRCTN (www.isrctn.com), registration number ISRCTN52684446 (retrospectively registered 02/08/19).
Stray dogs in Nepal have high prevalence of vector-borne pathogens: a molecular survey
Authors: Díaz-Regañón David , Agulla Beatriz , Piya Bidur , Fernández-Ruiz Natalia , Villaescusa Alejandra , García-Sancho Mercedes , Rodríguez-Franco Fernando , Sainz Ángel 
Published: April 2020

Abstract
Background
Population of stray dogs is significant in large cities of Nepal, such as Kathmandu. Most of stray dogs suffer a lack of basic health care. Considering the clinical relevance, the broad distribution and the lack of information of canine vector borne diseases (CVBD) in Nepal, the aim of this study was to evaluate the prevalence of different vector-borne pathogens (VBP) in stray dogs living in the metropolitan area of Kathmandu, and to assess different traits as possible risk factors.

Methods
A total of 70 canine blood samples from stray dogs attended at the Kathmandu Animal Treatment Centre during August 2017 were collected on filter paper (Flinders Technology Associates (FTA) cards). Data regarding signalment, clinical signs and epidemiological characteristics were recorded for each animal. Real-time polymerase chain reaction assays were performed for Leishmania spp., Ehrlichia spp./Anaplasma spp., Babesia spp./Theileria spp. and Hepatozoon canis.

Results
The overall prevalence detected was 31.43% for Hepatozoon canis, 31.43% for Anaplasma platys, 27.14% for Ehrlichia canis, 18.57% for Leishmania donovani species complex, 12.86% for isolates corresponding to Theileria spp., 12.86% for Babesia vogeli and 2.86% for B. gibsoni. A total of 81.43% of the dogs were positive to at least one of the VBP tested. Co-infections were detected in 41.43% of the dogs. Dogs positive to any of the VBP tested, and particularly to E. canis, were older than those that were negative.

Conclusions
To our knowledge, this is the first molecular detection of VBP in stray dogs from Kathmandu, Nepal. The high prevalence of VBP detected highlights the need to implement a surveillance programme and control strategies for these CVBD in the population of stray dogs in this area.
Rapid clearance of Borrelia burgdorferi from the blood circulation
Authors: Liang Liucun , Wang Jinyong , Schorter Lucas , Nguyen Trong Thu Phong , Fell Shari , Ulrich Sebastian , Straubinger Reinhard K. 
Published: April 2020

Abstract
Background
Borrelia burgdorferi is a tick-borne spirochete that causes Lyme borreliosis (LB). After an initial tick bite, it spreads from the deposition site in the dermis to distant tissues of the host. It is generally believed that this spirochete disseminates via the hematogenous route. Borrelia persica causes relapsing fever and is able to replicate in the blood stream. Currently the exact dissemination pathway of LB pathogens in the host is not known and controversially discussed.

Methods
In this study, we established a strict intravenous infection murine model using host-adapted spirochetes. Survival capacity and infectivity of host-adapted B. burgdorferi sensu stricto (Bbss) were compared to those of B. persica (Bp) after either intradermal (ID) injection into the dorsal skin of immunocompetent mice or strict intravenous (IV) inoculation via the jugular vein. By in vitro culture and PCR, viable spirochetes and their DNA load in peripheral blood were periodically monitored during a 49/50-day course post-injection, as well as in various tissue samples collected at day 49/50. Specific antibodies in individual plasma/serum samples were detected with serological methods.

Results
Regardless of ID or IV injection, DNA of Bp was present in blood samples up to day 24 post-challenge, while no Bbss was detectable in the blood circulation during the complete observation period. In contrast to the brain tropism of Bp, Bbss spirochetes were found in ear, skin, joint, bladder, and heart tissue samples of only ID-inoculated mice. All tested tissues collected from IV-challenged mice were negative for traces of Bbss. ELISA testing of serum samples showed that Bp induced gradually increasing antibody levels after ID or IV inoculation, while Bbss did so only after ID injection but not after IV inoculation.

Conclusions
This study allows us to draw the following conclusions: (i) Bp survives in the blood and disseminates to the host’s brain via the hematogenous route; and (ii) Bbss, in contrast, is cleared rapidly from the blood stream and is a tissue-bound spirochete.
Survival of Rickettsia conorii in artificially contaminated whole and leukoreduced canine blood units during the storage period
Authors: Lucchese Laura , Ravagnan Silvia , Da Rold Graziana , Toniolo Federica , Wurzburger Wendy , Mion Monica , Carminato Antonio , Fournier Pierre-Edouard , Capelli Gioia , Natale Alda , Vascellari Marta 
Published: April 2020

AbstractBackgroundThe ability of tick-borne agents to survive in stored blood bags is a key factor for their transmissibility by blood transfusion. The aim of this study was to evaluate the survival and potential infectivity ofRickettsia conorii(RC) in artificially contaminated canine whole blood (WB) and in leukoreduced whole blood (LR-WB) during the storage period.MethodsRC was cultured on L929 cells. We used a one-week 25-cm2flask with 70–80% of L929 infected cells to prepare the bacterial inoculum by pelleting cells and suspending the pellet in the donors’ serum. We infected five 100 ml WB units with RC within 2 h from the collection and maintained it at room temperature for 4 h prior to refrigeration. We filtered 50 ml of each WB bag to obtain leukoreduced WB (LR-WB) at day 1 post-infection (dpi). We checked WB and LR-WB bags at 1, 4, 7, 14, 21, 28, 35 dpi for RC presence and viability through real-time PCR (rPCR) for DNA and mRNA, respectively, and by isolation. Identification of isolates was confirmed by indirect immunofluorescence and rPCRs.ResultsRC survived for the entire storage period in both whole and leukoreduced blood. All bags contained viable bacteria until 7 dpi; RC viability generally decreased over time, particularly in LR-WB bags where the isolation time was longer than in WB. Viable bacteria were still isolated at 35 dpi in 3 WB and 3 LR-WB.ConclusionsLeukoreduction reduced but did not eliminate RC in infected units. The survival and infectivity of RC in canine blood during the storage period may represent a threat for recipients.
Monitoring Leishmania infection and exposure to Phlebotomus perniciosus using minimal and non-invasive canine samples
Authors: Maia Carla , Cristóvão José , Pereira André , Kostalova Tatiana , Lestinova Tereza , Sumova Petra , Volf Petr , Campino Lenea 
Published: April 2020

Abstract
Background
In endemic areas of zoonotic leishmaniosis caused by L. infantum, early detection of Leishmania infection in dogs is essential to control the dissemination of the parasite to humans. The aim of this study was to evaluate the serological and/or molecular diagnostic performance of minimally and non-invasive samples (conjunctiva cells (CS) and peripheral blood (PB)) for monitoring Leishmania infection/exposure to Phlebotomus perniciosus salivary antigens in dogs at the beginning and the end of sand fly seasonal activity (May and October, respectively) and to assess associated risks factors.

Methods
A total of 208 sheltered dogs from endemic areas of leishmaniosis were screened. Leishmania DNA detection in PB on filter paper and CS was performed by nested-PCR (nPCR), while the detection of anti-Leishmania antibodies was performed using IFAT and ELISA. The exposure to P. perniciosus salivary antigens (SGH, rSP01 and rSP03B + rSP01) was measured by ELISA.

Results
Ninety-seven (46.6%) and 116 (55.8%) of the 208 dogs were positive to Leishmania antibodies or DNA by at least one test at the beginning and end of the sand fly season, respectively. IFAT and ELISA presented a substantial agreement in the serodiagnosis of leishmaniosis. Discrepant PB nPCR results were obtained between sampling points. Leishmania DNA was detected in CS of 72 dogs at the end of the phlebotomine season. The presence of antibodies to the parasite measured by ELISA was significantly higher in dogs presenting clinical signs compatible with leishmaniosis at both sampling points. Phlebotomus perniciosus salivary antibodies were detected in 179 (86.1%) and 198 (95.2%) of the screened dogs at the beginning and end of the phlebotomine season, respectively.

Conclusions
The association between ELISA positivity and clinical signs suggests its usefulness to confirm a clinical suspicion. CS nPCR seems to be an effective and non-invasive method for assessing early exposure to the parasite. PB nPCR should not be used as the sole diagnostic tool to monitor Leishmania infection. The correlation between the levels of antibodies to P. perniciosus saliva and Leishmania antibodies suggests the use of a humoral response to sand fly salivary antigens as biomarkers of L. infantum infection.