bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lapatinib sensitivity in nasopharyngeal carcinoma is modulated by SIRT2-mediated FOXO3 deacetylation
Authors: Lam Eric W.-F. , Mahmud Zimam , Aimjongjun Sathid , Jiramongkol Yannasittha , Alasiri Glowi , Yao Shang , Yague Ernesto , Janvilisri Tavan 
Published: July 2019

Abstract
Chemoresistance is an obstacle to the successful treatment of nasopharyngeal carcinoma (NPC). To explore novel treatment strategies, we first characterized the lapatinib-sensitivity of a panel of NPC cell lines by SRB and clonogenic cytotoxic assays and found that the highly metastatic NPC (C666-1 and 5-8F) cells are significantly more resistant and the poorly metastatic lines (6-10B, TW01 and HK-1) more sensitive to lapatinib. Western blot analysis of the lapatinib-sensitive 6-10B and resistant 5-8F NPC cells showed that the expression of phosphorylated/inactive FOXO3(P-FOXO3;T32), its target FOXM1 and its regulator SIRT2 correlates negatively with lapatinib response and sensitivity, suggesting that SIRT2 mediates FOXO3 deacetylation to promote lapatinib resistance. In agreement, clonogenic cytotoxic assays using wild-type and foxo1/3/4−/− MEFs showed that FOXO1/3/4-deletion significantly attenuates lapatinib-induced cytotoxicity, confirming that FOXO proteins are essential for mediating lapatinib response. SRB cell viability assays using chemical SIRT inhibitors (i.e. sirtinol, Ex527, AGK2 and AK1) revealed that all SIRT inhibitors can reduce NPC cell viability, but only the SIRT2-specific inhibitors AK1 and AGK2 further enhance the lapatinib cytotoxicity. Consistently, clonogenic assays demonstrated that the SIRT2 inhibitors AK1 and AGK2 as well as SIRT2-knockdown increase lapatinib cytotoxicity further in both the sensitive and resistant NPC cells. Co-immunoprecipitation studies showed that besides lapatinib treatment, SIRT2-pharmaceutical inhibition and silencing also led to an increase in FOXO3 acetylation. Importantly, SIRT2 inhibition and depletion further enhanced lapatinib-mediated FOXO3-acetylation in NPC cells. Collectively, our results suggest the involvement of SIRT2-mediated FOXO3 deacetylation in lapatinib response and sensitivity, and that SIRT2 can specifically antagonise the cytotoxicity of lapatinib through mediating FOXO3 deacetylation in both sensitive and resistant NPC cells. The present findings also propose that SIRT2 can be an important biomarker for metastatic and lapatinib resistant NPC and that targeting the SIRT2-FOXO3 axis may provide novel strategies for treating NPC and for overcoming chemoresistance.
Level of birth preparedness for complication readiness plan and associated factors among women who gave live birth in Bahir Dar, Amhara regional state, Ethiopia, 2018
Authors: Ayalew Agumas Fentahun , Gelaw Asmare Yitayeh , Banite Getasew Mulat 
Published: July 2019

Abstract
Background

Birth preparedness and complication readiness is a safe motherhood strategy that addresses delays that could raise the risk of dying in pregnancy, childbirth and the immediate postpartum period. About 800 ladies pass daily due to pregnancy or childbirth-related complications worldwide. Nearly all maternal passing’s 99% occurred in low- and middle-income countries and more than half of these death happen in sub-Saharan Africa. So, the main objective of the study was to assess the level and factors associated with birth preparedness and complication readiness plan among women who gave live birth during the last one year in Bahir Dar City.

Methods

A Community based cross-sectional study design was conducted from May 10- 30/2018 in Bahir Dar City. Study participants were recruited by using a systematic random sampling technique. A pre-tested questionnaire was used to collect the data. The collected data were coded, entered and cleaned with EpiData version 3.1 and analyzed using SPSS version 23. Multivariable logistic regression was conducted to identify factors associated with Birth preparedness and complication readiness. The adjusted odds ratio with a 95% Confidence interval at a 5% level of significance was used to measure the strength of association.

Result

a total of 328 mothers with a response rate of 93.98% response rate. 46.65% of respondents were found in 18-24 years of age group. From the total respondents, 59.1% had good practice towards birth preparedness and complication readiness plan. Only 36% and 34.3% of respondents have good knowledge about pregnancy danger signs and labor danger signs, respectively.

Mothers Age (18–24) years [AOR=0.013; 0.001,0.228], Primary and below education level [AOR=0.01; 0.001, 0.038]; monthly income(<500 birr) [AOR=0.001; 0.001, 0.840], parity(1-2) [AOR=0.052; 0.007, 0.410], and family size (1-3) [AOR=0.048; 0.005, 0.432] were statistically significant associated variables with birth preparedness and complication readiness plan.

Conclusion

Extent of birth preparedness and complication readiness plan was found to be low as per government require. Maternal Age, Education, Monthly Income, Parity, and Family size were variables that affect birth preparedness and complication readiness plan significantly.

Key

Birth preparedness, complication readiness, women live birth, Bahir Dar
Associations of serum low-density lipoprotein and systolic blood pressure levels with type 2 diabetic patients with and without peripheral neuropathy: Systemic review, meta-analysis and meta-regression analysis of observational studies
Authors: Naqvi Syed Shah Zaman Haider , imani Saber , Hosseinifard Hossein , Shahzad M. Naveed , Ijaz Iqra , Wen QingLian , Guo Man , Xu Yong 
Published: July 2019

Abstract
Background: Compositional abnormalities in lipoproteins and cardiovascular risk factors play an important role in the progression of diabetic peripheral neuropathy (DPN). This systematic review aimed to estimate the predicting value of low-density lipoprotein (LDL) and systolic blood pressure (SBP) level in type-2 diabetes mellitus (T2DM) patients with and without peripheral neuropathy. We also tried to determine whether LDL and SBP are associated with an increased collision risk of DPN.
Materials and Methods: A systematic search was conducted for eligible publications which explored the LDL and SBP level in T2DM patients with and without peripheral neuropathy. The quality of the included studies was assessed by the QUADAS-2 tool. The standardized mean difference (SMD) with 95% CI of LDL and SBP level were pooled to assess the correlation between LDL and SBP level with DPN. We performed random effects meta-regression analyses to investigate factors associated with an increased collision risk of DPN.
Results: There was a significant association between LDL and SBP with poor prognosis of DPN in those included studies (I2 = 88.1% and I2 = 84.9%, respectively, Both P < 0.001). European T2DM patients have higher serum level of LDL in compare with the European DPN patients (SMD = 0.16, 95 % CI: -0.06 - 0.38; P < 0.001). SBP level was associated with a 2.6 fold reduce in non-DPN patients of T2DM (SMD = -2.63, 95% CI: -4.00 - -1.27, P < 0.001). Furthermore, the results of the case-control study design model are more precise to show the accuracy of SBP in Asian T2DM patients. Old age European T2DM patients have significantly low collision risk in the last 30 years for diabetes drivers that indicates that LDL and SBP levels could be a promising vulnerability biomarker for early detection and effective intervention of DPN in real-life clinical practice of individuals with T2DM.
Conclusion: Our finding supports the LDL and SBP status could be a promising prognostic biomarker for early detection and effective intervention of DPN in real-life clinical practice of individuals with T2DM.
Meta-gene markers predict meningioma recurrence with high accuracy.
Authors: Zador Zsolt , Landry Alexander , Haibe-Kains Benjamin , Cusimano Michael 
Published: July 2019

Abstract
Background: Meningiomas, the most common adult brain tumors, recur in up to half of cases[1–3]. This requires timely intervention and therefore accurate risk assessment of recurrence is essential. Our current practice relies heavily on histological grade and extent of surgical excision to predict meningioma recurrence. However, prediction accuracy can be as poor as 50% for low or intermediate grade tumors, which constitute more than 90% of all cases. Moreover, attempts to find molecular markers, particularly for predicting recurrence of intermediate tumors have been impeded by low[4] or heterogenous[5–8] genetic signal. We therefore sought to apply systems-biology approaches to transcriptomic data to better predict meningioma recurrence.

Methods: We apply gene co-expression networks to a cohort of 252 adult patients from the publicly-available genetic repository Gene Expression Omnibus. Resultant gene clusters (“modules”) were represented by the first principle component of their expression levels, and their ability to predict recurrence assessed with a logistic regression model. External validation was done using an independent merged cohort of 108 patients using the same modules. We used the bioinformatics database DAVID[9] to examine the gene ontology associations of each module.

Results: Using gene co-expression analysis, we were able predict tumor recurrence with high accuracy using a single module which mapped to cell cycle-related functions (AUC of 0.81 ± 0.09 in external validation). Further, the module maintained its accuracy with removal of up to 20 of it’s most individually predictive genes, suggesting robustness against noise at the single gene level.

Conclusions: With the easy accessibility of gene panels in healthcare diagnostics, our results offer a basis for routine molecular testing in meningioma management.
Multicenter randomized study on comparison between electronic and traditional chest drainage systems
Authors: Marulli Giuseppe , Comacchio Giovanni Maria , Nosotti Mario , Rosso Lorenzo , Mendogni Paolo , Natale Giuseppe , Andriolo Luigi , Imbriglio Giovanna , Larocca Valentina , Rea Federico 
Published: July 2019

Abstract
Background
In patients submitted to major pulmonary resection, post-operative length of stay is mainly influenced by duration of air leaks and chest tube removal. The measurement of air leaks largely relies on traditional chest drainage systems which are prone to subjective interpretation. Difficulty to differentiate between active air leaks and bubbles due to a pleural space effect may also lead to tentative drain clamping and prolonged time for chest drain removal. New digital systems allow continuous monitoring of air leaks, identifying subtle leakage that may be not visible during daily patient evaluation. Moreover, an objective assessment of air leaks may lead to a reduced interobserver variability and to an optimized timing of chest tube removal.

Methods
This study is a prospective randomized, interventional, multicenter trial designed to compare the electronic chest drainage system (Drentech™ Palm Evo) with the traditional system (Drentech™ Compact) in a cohort of patients undergoing pulmonary lobectomy through a standard 3-ports VATS approach for benign or malignant disease. It will enroll 382 patients in 3 Italian centers. Duration of chest drainage and length of hospital stay will be evaluated in the two groups. Moreover, it will be evaluated if the use of a digital chest system compared with a traditional system reduces the interobserver variability. Finally, it will be evaluated the possible advantages of the digital drain system to distinguish an active air leak from a pleural space effect, by the evaluation of intrapleural differential pressure, and to identify potential predictors of prolonged air leaks.

Discussion
To date few studies have been performed to evaluate clinical impact of digital drainage systems. The proposed prospective randomized trial will provide new knowledge to this research area by investigating and comparing the difference between digital and traditional chest drain systems. In particular, the objectives of this project are to evaluate the feasibility and usefulness of utilizing the digital chest drain and to provide new tools to identify patients at higher risk of developing prolonged air leaks.

Trial registration number
NCT03536130, Registered 24 May 2018 - Retrospectively registered, https://clinicaltrials.gov/ct2/results?cond=&term=NCT03536130&cntry=&state=&city=&dist=
Urban-Rural Disparities in Treatment Outcomes Among Recurrent TB Cases in Zambia
Authors: Mutembo Simon , Mutanga Jane Namangolwa , Musokotwane Kebby , Kanene Cuthbert , Dobbin Kevin , Li Changwe , Yao Xiaobai , Marconi Vincent , Whalen Christopher 
Published: July 2019

Abstract
Setting
Southern province, Zambia.
Background
At least 13 – 20% of all Tuberculosis (TB) cases are recurrent TB. Recurrent TB patients have high risk of Multi-Drug Resistant TB (MDR-TB).
Objective
To estimate the prevalence of recurrent TB among TB cases and compare risk of unfavorable treatment outcomes between rural and urban settings.
Methods
In a retrospective cohort study, we used mixed effects logistic regression to asses associations between explanatory and outcome variables. Primary outcome was all-cause mortality and exposure was setting (rural/urban).
Results
Overall 3,566 recurrent TB cases were diagnosed among 25,533 TB patients. The prevalence of recurrent TB was 15.3% in urban and 11.3% in rural areas. Death occurred in 197 (5.5%), 103 (2.9%) were lost to follow (LTFU), and 113 (3.2%) failed treatment. Rural settings had 70% higher risk of death (aOR: 1.7; 95% CI: 1.2 2.7). Risk of LTFU was twice higher in rural than urban (aOR: 2.0 95% CI: 1.3 3.0). Compared to HIV-uninfected, HIV-infected individuals on Antiretroviral Treatment (ART) were 70% more likely to die (aOR: 1.7; 95% CI: 1.2 3.1).
Conclusion
Recurrent TB prevalence was generally high in both urban and rural settings. The risk of mortality and LTFU was higher among rural patients. We recommend a well-organized Directly Observed Therapy strategy adapted to setting.
Recovery of non-reference sequences missing from the human reference genome
Authors: Li Ran , Tian Xiaomeng , Yang Peng , Fan Yingzhi , Li Ming , Zheng Hongxiang , Wang Xihong , Jiang Yu 
Published: July 2019

Abstract
The non-reference sequences (NRS) represent structure variations in human genome with potential functional significance. However, besides the known insertions, it is currently unknown whether other types of structure variations with NRS exist. Here, we compared 31 human de novo assemblies with the current reference genome to identify the NRS and their location. We resolved the precise location of 6,113 NRS adding up to 12.8 Mb. Besides 1,571 insertions, we detected 3,041 alternate alleles, which were defined as having less than 90% (or none) identity with the reference alleles. These alternate alleles overlapped with 1,143 protein-coding genes including a putative novel MHC haplotype. Further, we demonstrated that the alternate alleles and their flanking regions had high content of tandem repeats, indicating that their origin was associated with tandem repeats. Our study enriched the spectrum of human genetic variations.
Optimal Location of Subtrochanteric Osteotomy in Total Hip Arthroplasty for Crowe Type IV Developmental Dysplasia of Hip
Authors: Huang Zhe-Yu , Liu Hua , Li Ming , Ling Jing , Zhang Jun-Hui , Zeng Zhi-Min 
Published: July 2019

Abstract
Background

When reconstructing a hip with developmental dysplasia with high dislocation, sub-trochanteric shortening osteotomy is always needed for placing the acetabular component in the anatomical position. However, the procedure can result in some complications, such as the non-union of the osteotomy. We evaluated the contact area and coincidence rate between the proximal and distal fragments at different levels and lengths of femoral osteotomy and determined the optimal location of subtrochanteric femoral shortening transverse osteotomy in patients with unilateral Crowe type IV developmental dysplasia of the hip (DDH). The consistency between the proximal and distal segments was assessed as a possible predictive indicator of the union of the osteotomy site.

Methods

We retrospectively reviewed 57 patients with unilateral Crowe type IV DDH who underwent X-ray imaging of both hip joints. We labelled the inner and outer diameters of the circular ring as N (mm) and M (mm), respectively. We defined the area overlapped between the proximal and distal ring as contact area S (mm2), and the ratio of contact area to distal ring area as coincidence rate R.

Results

N varied from 9.8 to 15.2 and M varied from 20.7 to 24 mm, with both demonstrating a gradually decreasing trend in the proximal to distal direction. At the lengths of osteotomy ranging of 0.5–2 cm, there were no differences in S between the different levels of osteotomy in each group. At lengths of osteotomy ≤ 2.5 cm, a significant higher coincidence rate was noted from the level of 2 cm below the lesser trochanter to other positions below the level. At lengths of osteotomy of 3–5.5 cm, a significantly higher coincidence rate was observed from the level of 1.5 cm below the lesser trochanter to other positions below the level.

Conclusions

Our findings suggest that femoral shortening transverse osteotomy at the optimal subtrochanteric level can predictably increase the contact area and coincidence rate, which may contribute to the union at the osteotomy site. In consideration of the stability of the prostheses, it appears appropriate that the location of osteotomy should be slightly shifted distally.
Multiplex qPCR Facilitates Identification of Betaherpesviruses in Patients With Acute Liver Failure of Unknown Etiology
Authors: Raposo Jéssica Vasques , Alves Arthur Daniel Rocha , Silva Alexandre Dos Santos Da , Santos Damião Carlos Dos , Melgaço Juliana Gil , Moreira Otacilio Cruz , Pinto Marcelo Alves , de Paula Vanessa 
Published: July 2019

Abstract
Background: The etiology of acute liver failure (ALF) is often unknown and reported to be associated with herpesviruses in a number of cases. In this study, we examined for betaherpesviruses infections in patients with ALF of unknown etiology using a multiplex qPCR to Betaherpesviruses subfamily.
Methods: Liver explant and serum samples from 27 patients with ALF of unknown etiology were analyzed with the aid of multiplex qPCR to identify betaherpesviruses. All positive samples were sequenced to confirm herpes infection and liver enzyme levels evaluated.
Results: Betaherpesviruses infection was effectively detected using multiplex qPCR. Six (22%) HHV-6, one (3%) HCMV and two (7%) dual infections (one with HHV-7/HHV-6, and the other with HHV-7/ HCMV). Interestingly, HHV-7 was only detected in the presence of other betaherpesviruses. Sequencing information confirmed betaherpesviruses infection. High hepatic enzyme levels and INR values>1.5 were determined in all betaherpesvirus-positive patients.
Conclusions: Multiplex qPCR facilitated efficient quantification, indicating that differentiation between betaherpesviruses is possible with the sole use of real-time PCR. Liver explant and serum samples were positive for some betaherpesviruses, and coinfection of HHV-7 with HHV-6 and HCMV was additionally detected. Based on these results, we propose that ALF patients should be screened for the presence of betaherpesviruses.
Genetic Diversity and Epidemiology of Genogroup II Noroviruses in Children with Acute Sporadic Gastroenteritis in Shanghai, China, 2012-2017
Authors: Lu Lijuan , Zhong Huaqing , Xu Menghua , Su Liyun , Cao Lingfeng , Jia Ran , Xu Jin 
Published: July 2019

Abstract
Background Noroviruses (NoVs) are considered an important cause of acute gastroenteritis (AGE) across all age groups, especially in children under five years of age. We investigated the epidemiology of noroviruses in outpatient children from the Children’s Hospital of Fudan University in Shanghai, China. Methods Stool specimens were collected between January 2012 and December 2017 from 1433 children under ﬁve years of age with acute gastroenteritis. All samples were analysed by conventional reverse transcription-polymerase chain reaction (RT-PCR) for genogroup II NoVs amplifying both the RNA-dependent RNA polymerase (RdRp) and partial capsid genes. The Norovirus Genotyping Tool v.2.0 (https://www.rivm.nl/mpf/typingtool/norovirus/) was used for genotyping the strains, and phylogenetic analyses were conducted by MEGA 6.0. Results From 2012 to 2017, GII NoVs were detected in 15.4% (220/1433) of the samples, with the highest detection rate in children aged 7-12 months (19.2%, 143/746). The seasons with the highest prevalence of GII NoVs infection were autumn and winter . Based on genetic analysis of RdRp, GII.Pe (74.5%%, 137/184) was the most predominant RdRp genotype from 2013 to 2017, while GII.P4 played a dominant role in 2012 (55.6%, 21/36). Among the capsid genotypes, the most prevalent NoV genotype from 2012 to 2017 was GII.4 (73.6%, 162/220). On the basis of genetic analysis of RdRp and capsid sequences, the strains were clustered into 19 RdRp/capsid genotypes, and 12 of them were discordant, such as GII.Pe/GII.4-Sydney_2012, GII.P12/GII.3, GII.P7/GII.6, GII.Pe/GII.3, and GII.P16/GII.2. Starting with 2013, GII.Pe/GII.4-Sydney_2012 had completely replaced the pandemic GII.P4-2006b/GII.4-2006b subtype and was detected in children across all age groups. Conclusions The present study shows high detection rates and the genetic diversity of circulating NoV GII genotypes in paediatric AGE samples from Shanghai. The findings emphasize the importance of continuous molecular surveillance of emerging NoV strains.
Evaluation of the Glucuronic Acid Production and Antibacterial Properties of Kombucha Black Tea
Authors: Ansari Fereshteh , Pourjafar Hadi , Kangari Ali , Homayouni Aziz 
Published: July 2019

Background:
Kombucha beverage is considered as a dietary supplement and drinking it
strengthens the body’s immune system which prevents diseases.

Objective:
The purpose of this study was to determine the amount of glucuronic acid and antibacterial
activity of Kombucha black tea drink during its production at different storage temperature.

Methods:
The extent of glucuronic acid at temperatures of 20°C and 30°C was explored by the use of
the HPLC system for 21 days. To analyse the antibacterial property, the influence of Kombucha black
tea supernatant on the growth of Salmonella typhimurium, Staphylococcus aureus, and Lactobacillus
rhamnosus bacteria was examined via the two procedures of the disc and agar well diffusion.

Results:
The production of glucuronic acid underwent a variation at 20°C from 17.0 mg/L on day 1 to
roughly 27.2 mg/L on day 21, and the difference was significant. Furthermore, the quantity of this acid
at 30°C increased from 42.2 mg/L on day 1 to 48.0 mg/L on day 21. The amount of glucuronic acid
produced at 30°C was significantly greater than that at 20°C (p<0.05). This study indicated that the
Kombucha black tea has antibacterial activity against Salmonella typhimurium and Staphylococcus
aureus, but not against Lactobacillus rhamnosus. However, there are no statistical differences in
antibacterial activity of Kombucha between incubation at 20oC and 30oC (P>0.05).

Conclusion:
This study offers a perspective on glucuronic acid production (especially in 30°C rather
than 20°C) and antibacterial activity of Kombucha black tea beverage.