bluuebunny/crossref_metadata_2025_split huggingface dataset:
What proportion of care home outbreaks are caused by norovirus? An analysis of viral causes of gastroenteritis outbreaks in care homes, North East England, 2016-2018
Authors: Inns Thomas , Wilson Deb , Manley Petra , Harris John P , O’Brien Sarah J , Vivancos Roberto 
Published: July 2019

Abstract
Background

Outbreaks of infectious gastroenteritis are common in care homes for the elderly. Norovirus can cause these outbreaks, but diagnosis is frequently based solely on clinical characteristics. Our objective in this study was to describe the epidemiology of norovirus and other gastrointestinal pathogens in these settings.

Methods

We analysed surveillance data from gastroenteritis outbreaks reported in North East England between 04 July 2016 to 01 July 2018. Stool samples taken during these outbreaks were tested for a range of viral and bacterial pathogens. We described the epidemiology of these outbreaks and explored the characteristics of norovirus outbreaks versus from other viral causes using multivariable logistic regression.

Results

From the 566 care home gastroenteritis outbreaks in this study, we found that norovirus was the pathogen most frequently isolated. Norovirus was detected in 64% of outbreaks with submitted stool samples. Sapovirus was found in 13%; rotavirus in 11%. We found that norovirus outbreaks were associated with higher attack rates (aOR 5.92, 95% CI 2.30-16.50) and larger care homes (aOR 2.35, 95% CI 1.05-5.38), compared to outbreaks caused by other viral pathogens.

Conclusions

These results are important as they quantify the contribution of norovirus to gastroenteritis outbreaks in care homes. Given this evidence, we emphasize the importance of non-specific outbreak interventions that can affect the impact of all such outbreaks. We further recommend that these findings are used to inform the implementation strategies of any norovirus-specific interventions such as a norovirus vaccine.
Sepsis in cancer patients residing in Zimbabwe: Spectrum of bacterial and fungal aetiologies and their antimicrobial susceptibility patterns.
Authors: CHINOWAITA FRANK , Chaka Wendy , Nyazika Tinashe K , Maboreke Tendai C , Chitsike Inam , Cakana Andrew Z , Tizauone Emmanuel , Mapondera Prichard , Mavenyengwa Rooyen Tinago 
Published: July 2019

Abstract
Introduction: Cancer and sepsis comorbidity is a major public health problem in most parts of the world including Zimbabwe. The microbial aetiologies of sepsis and their antibiograms vary with time and locations. Knowledge on local microbial aetiologies of sepsis and their susceptibility patterns is critical in guiding empirical antimicrobial treatment choices.
Methods: This was a descriptive cross sectional study which determined the microbial aetiologies of sepsis from blood cultures of paediatric and adult cancer patients obtained between July 2016 and June 2017. The TDR-X120 blood culture system and TDR 300B auto identification machine were used for incubation of blood culture bottles and identification plus antimicrobial susceptibility testing, respectively.
Results: A total of 142 participants were enrolled; 50 (35.2%) had positive blood cultures with 56.0% gram positive, 42.0% gram negative bacteria and 2.0% yeast isolates. Most common isolates were Coagulase Negative Staphylococcus (CoNS) (22.0%), Escherichia coli (16.0%), Klebsiella pneumoniae (14.0%), Enterococcus faecalis (14.0%) and Staphylococcus aureus (8.0%) in all cancer patients. These isolates were similar in both haematological and solid cancers. Amikacin and meropenem showed 85.7% and 95.2% activity respectively against all gram negative isolates while vancomycin and linezolid were effective against 96.2% and 100.0% of all gram positive isolates respectively. Ten (66.7%) isolates of E. coli and K. pneumoniae were extended spectrum β-lactamase (ESBL) positive and the same proportion was observed on methicillin resistance among Staphylococcus species.
Conclusions: The major microbial aetiologies of sepsis among patients with cancer in Zimbabwe were CoNS, E. coli, K. pneumoniae, E. faecalis and S. aureus. Most isolates were resistant to commonly used empirical antibiotics and there was high level of ESBL and methicillin resistance carriage. A nationwide survey on microbial aetiologies of sepsis and their susceptibility patterns would assist in the guidance of effective sepsis empiric antimicrobial treatment among patients with cancer.
The seasonal development dynamics of the yak hair cycle transcriptome
Authors: Bao Pengjia , Luo Jiayu , Liu Yanbin , Chu Min , Ren Qingmiao , Guo Xian , Tang Bolin , Ding Xuezhi , Qiu Qiang , Pan Heping , Wang Kun , Yan Ping 
Published: July 2019

Abstract
Background: Mammalian hair play an important role in mammals' ability to adapt to changing climatic environments. The seasonal circulation of yak hair helps them adapt to high altitude but the regulation mechanisms of the proliferation and differentiation of hair follicle (HF) cells during development are still unknown. Here, using time series data for whole genome expression profiles and hormone contents, we systematically analyzed the mechanism regulating the periodic expression of hair development in the yak and reviewed how different combinations of genetic pathways regulate HF development and cycling.

Results: This study used high-throughput RNA sequencing to provide a detailed description of global gene expression in 15 samples from five developmental time points during the yak hair cycle. A total of 11,666 genes were found to be involved in the hair cycle. According to clustering analysis and the morphological features we observed, we found that these 15 samples could be significantly grouped into three phases, which represent different developmental periods in the hair cycle. A total of 2,316 genes were identified in these three consecutive developmental periods and their expression patterns could be divided into 9 clusters; GO annotation and KEGG pathway enrichment were performed on these differentially expressed genes (DEGs), showing that the three periods have distinctive functions in the seasonal hair cycle. The regulatory network of related signaling factors highlighted the interaction and dynamic expression of key DEGs during the seasonal hair cycle. Through co-expression analysis, we revealed a number of modular hub genes highly associated with hormones that may play unique roles in hormonal regulation of events associated with the hair cycle.

Conclusions: Our results revealed the molecular mechanisms and developmental regulatory networks of the seasonal hair cycle in the yak and filled a gap in the current research field. The findings will be valuable in further understanding the alpine adaptation mechanism in the yak, which is important in order to make full use of yak hair resources and promote the economic development of pastoral plateau areas.

Keywords: Hair cycle, Seasonal development, Transcriptome, Yak
ATR Signalling mediates the prosurvival function of phospho-NPM against PIDDosome mediated cell death
Authors: Hiregange Disha , Naick Hemanth , Rao Basuthkar J 
Published: July 2019

Abstract
Background:

ATR kinase is studied largely in the context of externally imposed genotoxic stress, even though its endogenous basal level plays important homeostatic cellular functions.

Results:

We show that pNPM triggers the dissociation of NPM from P1DD thus preventing the cell from undergoing caspase 2 mediated cell death via PIDDosome, thereby acting as an endogenous negative regulator keeping the PIDDosome activation under check. pChk1 interacts with NPM before phosphorylating it, which is abrogated following ATR kinase inhibition, dropping nucleoplasmic/chromatin pNPM level, thereby inducing PIDD. Expectedly, phosphodead mutants of Chk1 and NPM are not viable as the pNPM regulatory axis is abrogated, whereas the phosphomimic mutants of Chk1 and NPM render cells refractory to ATR/pChk1 kinase inhibition induced cell death. Interestingly, cells expressing phosphomimic mutant of Chk1(S345E) withstand ATRi, but not Chk1i mediated PIDDosome activation implying that the Chk1 kinase plays a direct role in pNPM homeostasis, even in the absence of replication stress.

Conclusion:

In the current study, we uncover the non-canonical role of ATR kinase in the control of PIDDosome activation, and show that under normal cellular conditions involving no replication stress, ATR kinase controls the phosphorylation of NPM via pChk1 and the two phosphatases regulating pNPM, namely, PPM1D and PP1β.
Detection of 8-oxoguanine and Apurinic/Apyrimidinic Sites Using a Fluorophore-Labeled Probe With Cell-penetrating Ability
Authors: Kang Dongmin , Shin Jong-Il , Kim Ji Beom , Lee Kyungho , Chung Ji Hyung , Yang Hye-Won , Kim Kil-Nam , Han Ye Sun 
Published: July 2019

Abstract
Background

Detection and quantification of 8-oxo-7,8-dihydroguanine (8-oxoG) within cells are important for studying the molecular mechanisms of cancer. Human ribosomal protein S3 (hRpS3), which is involved in DNA repair, has a high binding affinity to 8-oxoG. We developed an imaging probe to detect 8-oxoG using a specific peptide from hRpS3. Transactivator (TAT) proteins are commonly known to have cell-penetrating properties. Therefore, we developed the TAT-S3 probe via attaching a TAT peptide to our imaging probe.

Result

A DNA binding assay was conducted to confirm that our probe bound to 8-oxoG and AP sites. We confirmed that the TAT-S3 probe is present in the mitochondria, without permeabilization, and the TAT-S3 probe also showed fluorescence in H2O2-treated HeLa cells and zebrafish embryos. Treatment with MitoQ, a mitochondria-targeted anti-oxidant, reduced TAT-S3 probe fluorescence. Additionally, treatment with O8, an inhibitor of OGG1, increased probe fluorescence. A competition assay was conducted to utilize an aldehyde reaction probe (ARP) and methoxyamine (MX) to confirm the binding of the TAT-S3 to the AP sites. The TAT-S3 probe showed binding to AP sites competitive with ARP and MX.

Conclusion

These results revealed that the TAT-S3 probe successfully detected the presence of 8-oxoG and AP sites in damaged cells. The TAT-S3 probe may have applications for the detection of diseases caused by reactive oxygen species (ROS).
Fibroblast Growth Factor 2 Augments Transforming Growth Factor Beta 1 in Inducing Epithelial-Mesenchymal Transition in Human Lung Epithelial Cells
Authors: El-Baz Lamis M.F. , Shoukry Nahla M. , Salem Mohamed L. , Hafez Hani S. , Guzy Robert D. 
Published: July 2019

Abstract
Background: Epithelial-mesenchymal transition (EMT) is a critical event in wound healing and tissue repair following injury. Transforming growth factor beta-1 (TGFβ1) plays an important role in inducing EMT in lung epithelial cells in vitro and in vivo. As fibroblast growth factor-2 (FGF2) reverses TGFβ1-induced collagen I (COL1A1) and α-smooth muscle actin (Actin alpha 2; ACTA2) expression in primary mouse and human lung fibroblasts, we set out this study to determine the effect of FGF2 on TGFβ1-induced EMT in human lung epithelial cells.
Methods: BEAS-2B and A549 cells were treated with recombinant FGF2 (2 nM) with or without TGFβ1 (2 ng/ml) for up to 4 days. The phenotypic alterations associated with EMT were assessed by quantitative real-time PCR and E-cadherin protein expression levels was assayed by western blot and immunofluorescence staining. Cell migration was confirmed using wound-healing assay.
Results: TGFβ1 treatment led to significantly reduced expression of E-cadherin (CDH1) and markedly induced expression of mesenchymal proteins such as N-cadherin (CDH2), tenascin C (TNC), fibronectin (FN), ACTA2 and COL1A1. TGFβ1 also induced a morphological change and a significant increase in cell migration. FGF2 did not significantly alter EMT gene expression markers on its own, however enhanced TGFβ1-induced suppression of CDH1 and upregulation of ACTA2, but did not alter TNC, FN and CDH2 gene expression levels induced by TGFβ1. FGF2 maintained TGFβ1-induced morphologic changes as well as increased the migration of TGFβ1-treated cells. Furthermore, FGF2 treatment significantly inhibited TGFβ1-induced COL1A1 expression in both BEAS-2B and A549 cells. FGFR-specific tyrosine kinase inhibitor PD173074 blocked the synergism between these two growth factors.
Conclusions: This study suggests a synergistic effect between TGFβ1 and FGF2 in inducing EMT, which may play an important role in wound healing and tissue repair after injury. Our findings provide insight into the effects of FGF2 following lung injury and in pulmonary fibrosis.
Global diastolic strain rate for the assessment of left ventricular diastolic dysfunction in young peritoneal dialysis patients: a case control study
Authors: Zhu Jing , Shi Fei , You Tao , Tang Chao , Chen Jianchang 
Published: July 2019

Abstract
Abstract
Background: Left ventricular (LV) myocardial longitudinal diastolic strain rate measured by two-dimensional speckle tracking imaging (2D-STI) was proved to have a better correlation with the LV diastolic function. We aimed to use this sensitive tool to predict LV myocardial diastolic dysfunction in young peritoneal dialysis (PD) patients with preserved LV ejection fraction (LVEF).
Methods: We enrolled 30 PD patients aged ≤60 with LVEF ≥54% and classified as normal LV diastolic function by conventional echocardiography, and 30 age- and sex-matched healthy people as the control group. The left atrial maximum volume index (LAVI), LV mass index (LVMI), LVEF, LV posterior wall thickness (LVPWT), interventricular septal thickness (IVST), peak velocity of tricuspid regurgitation (TR), peak early diastolic velocity/late diastolic velocity(by Pulsed Doppler) (E/A) and E/peak velocity of the early diastolic wave (by Pulsed-wave tissue Doppler) (E/e’) were recorded by conventional echocardiographic. Next, the average LV global longitudinal systolic strain (GLS avg) and the average LV global longitudinal diastolic strain rate (DSr avg) during early diastole (DSrE avg), late diastole (DSrA avg) and isovolumic relaxation period (DSrIVR avg) were obtained from 2D-STI. Combined them with E, the new noninvasive indexes (E/DSrE avg, E/DSrA avg and E/DSrIVR avg) were derived.
Results: The PD group ’s LVEF, E/e, TR and LAVI were in the normal range compared with the controls, and only e (p<0.001) was decreased. The LVMI (p<0.001), LVPWT (p<0.001), IVST (p<0.001) increased while E/A (p<0.001) decreased. The GLS avg (p=0.008) was significantly decreased in PD patients compared with the controls. DSrA avg (p=0.006) and E/DSrE avg (p=0.006) were increased, while DSrE avg (p<0.001), DSrIVR avg (p=0.017) and E/DSrA avg (p<0.001) decreased. After the multivariable regression analysis, the correlation between DSrE and the conventional parameters including LVPWT (p<0.001), E/A (p<0.001) still remained significant.
Conclusions: Young PD patients with preserved LVEF already exhibited myocardial diastolic dysfunction. Global diastolic strain rates such as DSrE, E/DSrE, DSrA, E/DSrA, and DSrIVR were valuable parameters to evaluate diastolic dysfunction. Additionally, LVPWT and E/A significantly influenced DSrE, such parameters should be taken into account for predicting the LV diastolic dysfunction in clinical practice.
Parathyroidectomy is a reliable treatment option for chronic kidney disease patients with secondary hyperthyroidism (SHPT)
Authors: Xing Changying , Cui Hongqing , Wu Jingjing , Zhang Li , Mao Chunxia , Huang Baodi , Mao Huijuan , Wang Ningning , Zhang Bo , Ren Haibin 
Published: July 2019

Abstract
Background: Secondary hyperthyroidism (SHPT) is a common complication in chronic kidney disease patients undergoing peritoneal dialysis. It develops as a result of distortions in the regulation of calcium, phosphorus and parathyroid hormone (PTH). SHPT increases with decreasing kidney function. Factors that affect the levels of calcium, phosphorus, and PTH include diet, residual renal function, peritoneal transport properties, and dialysate calcium concentration. Treatment options for SHPT include pharmaceutical and surgical removal of parathyroid glands. Although there are treatment options for kidney disease patients with SHPT, little improvement has been made in the overall outcome of the patients.
Method: Here, we present that parathyroidectomy is a treatment option for patients with SHPT. A test group (peritoneal dialysis patients with SHPT who had surgery plus forearm transplantation) were compared with control group (normal peritoneal dialysis patients without surgery). In both groups, clinical, biochemical and haematological profile assessments were done.
Results: The test group after surgery show improved clinical, biochemical and haematological profile comparing with the control (non-surgery) group.
Conclusion: parathyroidectomy (PTX) is a reliable treatment option for patients with SHPT, which brings about improvement in the biochemical, haematological, physiological and clinical parameters as compared with peritoneal dialysis patients with secondary hyperthyroidism without parathyroidectomy plus forearm transplantation.
Efficacy and safety of sodium zirconium cyclosilicate in patients with baseline serum potassium level ≥5.5 mmol/L: pooled analysis from two phase 3 trials
Authors: Amin Alpesh , Menoyo Jose , Singh Bhupinder , Kim Christopher S. 
Published: July 2019

Abstract
Background: Reliable, rapidly-acting, oral treatments for patients with hyperkalemia are needed. We examined the efficacy and safety of sodium zirconium cyclosilicate (SZC; formerly ZS-9) treatment for ≤48 hours in patients with baseline serum potassium level ≥5.5 mmol/L.
Methods: Data were pooled from two phase 3 studies (ZS-003 and HARMONIZE) among patients receiving SZC 10 g three times daily. Outcomes included mean and absolute change from baseline, median time to potassium level ≤5.5 and ≤5.0 mmol/L, and proportion achieving potassium level ≤5.5 and ≤5.0 mmol/L at 4, 24, and 48 hours. Outcomes were stratified by baseline potassium. Safety outcomes were evaluated.
Results: At baseline, 125 of 170 patients (73.5%) had potassium level 5.5–<6.0, 39 (22.9%) had potassium level 6.0–6.5, and 6 (3.5%) had potassium level >6.5 mmol/L. Regardless of baseline potassium, mean potassium decreased at 1-hour post-initial dose. By 4 and 48 hours, 37.5% and 85.0% of patients achieved potassium level ≤5.0 mmol/L, respectively. Median (95% confidence interval) times to potassium level ≤5.5 and ≤5.0 mmol/L were 2.0 (1.1–2.0) and 21.6 (4.1–22.4) hours, respectively. Fifteen patients (8.8%) experienced adverse events; none were serious.
Conclusions: SZC 10 g three times daily achieved rapid potassium reduction and normokalemia, with a favorable safety profile.
ClinicalTrials.gov identifiers: NCT01737697 and NCT02088073
SOFA score is superior to APACHE-II score in predicting the prognosis of critically ill patients with acute renal injury undergoing continuous renal replacement therapy
Authors: Wang Hai , Shi Yu , Bai Zheng-hai , LV Jun-hua , Sun Jiang-li , Pei Hong-hong , Zhang Zhengliang 
Published: July 2019

Abstract
Background: Acute renal injury (AKI) is the most common cause of organ failure in multiple organ dysfunction syndrome and is associated with higher mortality, especially for patients requiring continuous renal replacement therapy (CRRT). At present, no effective approaches are in place to predict the prognosis of patients with AKI undergoing CRRT.
Methods: A retrospective cohort study was carried to determine whether sequential organ failure assessment (SOFA) score may be a more valuable prognostic indicator than acute physiology and chronic health evaluation II (APACHE-II) score in patients with AKI undergoing CRRT. The multivariate analysis, sensitivity analysis, receiver operating characteristics (ROC) curve and decision curve analysis (DCA) were performed to determine the predictive value of SOFA and APACHE-II scores on 28- and 90-day mortality.
Results: From January 2009 to September 2016, a total of 1128 cases were included. Multivariate logistic regression analysis showed that both APACHE-II and SOFA scores were associated with 28- and 90-day mortality of patients with AKI undergoing CRRT. The adjusted odds ratios (ORs) for SOFA and APACHE-II scores associated with 28-day mortality were 1.38 (1.27, 1.51) and 1.04 (1.01, 1.07), respectively, and the adjusted ORs for SOFA and APACHE-II scores associated with 90-day mortality were 1.40 (1.28, 1.52) and 1.04 (1.01, 1.07), respectively. decision curve analysis and receiver operating characteristics analyses showed that SOFA had a higher prediction accuracy than APACHE-II for 28- and 90-day mortality. The AUCs of SOFA and APACHE-II for 28-day mortality were 0.70 (0.67, 0.73) and 0.62 (0.58, 0.65), and for 90-day mortality, the AUCs were 0.71 (0.68, 0.78) and 0.62 (0.58, 0.65), respectively.
Conclusion: SOFA score revealed higher accuracy than APACHE-II score in predicting the prognosis of critically ill patients with AKI undergoing CRRT.
A prospective risk assessment of the implementation of a Schistosomiasis Preventive Mass Drug Administration for children aged below five years in the uMkhanyakude District of KwaZulu-Natal
Authors: Ncube Mhlengi Vella , Chimbari Moses John 
Published: July 2019

Abstract
Background
Schistosomiasis is endemic in the uMkhanyakude district of KwaZulu-Natal, South Africa. The South Africa Department of Health (DoH) has decided to implement a schistosomiasis preventive mass drug administration program in all affected parts of the country. Quality management is part of the strategic objectives of the treatment program. We conducted a risk assessment and developed guidelines for the quality management of a schistosomiasis preventive treatment program for children aged five years and below in the uMkhanyakude District of KwaZulu-Natal.
Methods
We conducted a scenario planning exercise by interviewing 10 child health experts from the uMKhanyakude Health District to establish potential risks associated with a planned schistosomiasis preventive control treatment program for children aged five years old and below. The risks were analyzed using a modified Failure Mode and Effect Analysis (FMEA). An FMEA table was produced to guide the quality management of the planned schistosomiasis preventive control treatment program for children aged five years and below in the uMkhanyakude Health District.

Results
We identified potential risks, failure modes and possible failure corrective/preventive measures in the following activities that would be part of the mass treatment of children aged five years and below infected with schistosomiasis in the uMkhanyakude District. These included enrolment of children into the treatment program; general health checks; weight and height measurements; administration of drugs; reporting of side effects and monitoring and evaluation.
Conclusion
We were able to use FMEA guide quality management and identify potential risks associated with the planned schistosomiasis preventive treatment program for children aged five years old and below in the uMkhanyakude District of KwaZulu-Natal. The FMEA for this program will be useful to the quality management of schistosomiasis preventive treatment programs for this age group in other similar settings.