bluuebunny/crossref_metadata_2025_split huggingface dataset:
PFKFB4 is overexpressed in clear-cell renal cell carcinoma promoting pentose phosphate pathway that mediates Sunitinib resistance
Authors: Feng Chenchen , Li Yuqing , Li Kunping , Lyu Yinfeng , Zhu Wenhui , Jiang Haowen , Wen Hui 
Published: September 2021

Abstract
Background
Kinases play critical role in clear-cell renal cell carcinoma (ccRCC). We aim to exploit novel kinase that is both protumorigenic and drugable in ccRCC.

Methods
Reproduction of public datasets with validation using microarray was performed to identify candidate gene. Functionality was studied using multi-omics with validation in vitro and in vivo.

Results
6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 4 (PFKFB4) was differentially expressed showing significantly higher expression in tumor than in normal kidney. PFKFB4 overexpression was associated with advanced tumor grade, stage and worsened prognosis. PFKFB4-knockdown significantly impaired fitness in cell proliferation, migration and wound healing. Despite being recurrently deleted on 3p, PFKFN4 mRNA remained actively transcribed by HIF1α. Metabolomics showed overexpressed PFKFB4 showed enriched metabolites in pentose phosphate pathway (PPP). Phosphoproteomics and immunoprecipitation showed PFKFB4 also phosphorylated NCOA3 which interacted with FBP1 to counteract overactive PPP flux, forming a regulatory loop. PFKFB4-knockdown overcame resistance to Sunitinib in vitro and in vivo both in xenograft and tail-vein injection murine models.

Conclusion
We concluded PFKFB4 was associated with PPP activity and the fine-tuning of which was mediated by its phosphorylation of NCOA3. Targeting PFKFB4 held promise to combat resistance to Sunitinib.
Hypertrophic cardiomyopathy in infant newborns of diabetic mother: a heterogeneous condition, the importance of anamnesis, physical examination and follow-up
Authors: Codazzi Alessia Claudia , Ippolito Rosario , Novara Cecilia , Tondina Enrico , Cerbo Rosa Maria , Tzialla Chryssoula 
Published: September 2021

Abstract
Background
Hypertrophic cardiomyopathy (HCM) in neonates is a rare and heterogeneous disorder. HCM accounts for 25 to 40% of all pediatric cardiomyopathy cases and the highest incidence in pediatric population is reported in children < 1 year.

Case presentation
we report two clinical cases of neonates, born to mothers respectively with a pre-pregnancy insulin-dependent diabetic mellitus type 2 and a suspected diabetes, with inadequate prenatal glycemic control for the first and underestimated glycemic control for the second case, with a different evolution.
In the first case, a slow evidence of improvement of the HCM was observed, persuading us to the diagnosis of a diabetes-related HCM; In the second case the progressive worsening of the HCM during follow-up in association with further investigations, resulted in the diagnosis of Pompe disease.

Conclusions
Hypertrophic cardiomyopathy in newborns can be the clinical expression of different underlying disorders. We aim to show the importance both to reassess maternal and family history and critically evaluate the physical examination in order to address the correct differential diagnosis. Furthermore it is important to continue a regular cardiologic follow-up for this pathology with neonatal onset to prevent a poor prognosis.
The endemic Helicobacter pylori population in Southern Vietnam has both South East Asian and European origins
Authors: Nguyen Trang Hoa , Ho Trang Thi My , Nguyen-Hoang Thien-Phuc , Qumar Shamsul , Pham Thuc Tran Dang , Bui Quy Nhuan , Bulach Dieter , Nguyen Thuy-Vy , Rahman Motiur 
Published: September 2021

Abstract
Background
The burden of Helicobacter pylori-induced gastric cancer varies based on predominant H. pylori population in various geographical regions. Vietnam is a high H. pylori burden country with the highest age-standardized incidence rate of gastric cancer (16.3 cases/100,000 for both sexes) in Southeast Asia, despite this data on the H. pylori population is scanty. We examined the global context of the endemic H. pylori population in Vietnam and present a contextual and comparative genomics analysis of 83 H. pylori isolates from patients in Vietnam.

Results
There are at least two major H. pylori populations are circulating in symptomatic Vietnamese patients. The majority of the isolates (~ 80%, 66/83) belong to the hspEastAsia and the remaining belong to hpEurope population (~ 20%, 17/83). In total, 66 isolates (66/83) were cagA positive, 64 were hspEastAsia isolates and two were hpEurope isolates. Examination of the second repeat region revealed that most of the cagA genes were ABD type (63/66; 61 were hspEastAsia isolates and two were hpEurope isolates). The remaining three isolates (all from hspEastAsia isolates) were ABC or ABCC types. We also detected that 4.5% (3/66) cagA gene from hspEastAsia isolates contained EPIYA-like sequences, ESIYA at EPIYA-B segments. Analysis of the vacA allelic type revealed 98.8% (82/83) and 41% (34/83) of the strains harboured the s1 and m1 allelic variant, respectively; 34/83 carried both s1m1 alleles. The most frequent genotypes among the cagA positive isolates were vacA s1m1/cagA + and vacA s1m2/cagA + , accounting for 51.5% (34/66) and 48.5% (32/66) of the isolates, respectively.

Conclusions
There are two predominant lineages of H. pylori circulating in Vietnam; most of the isolates belong to the hspEastAsia population. The hpEurope population is further divided into two smaller clusters.
Reporting quality evaluation of the stroke clinical practice guidelines: a systematic review
Authors: Lu Shuya , Luo Xufei , Ni Xiaojia , Li Haoxuan , Meng Miaomiao , Cai Yefeng , Liu Yunlan , Ren Mengjuan , Sun Yanrui , Chen Yaolong 
Published: September 2021

AbstractObjectivesTo analyze the effectiveness and quality of stroke clinical practice guidelines (CPGs) published in recent years in order to guide future guideline developers to develop better guidelines.ParticipantsNo patient involvedMethodPubMed, China Biology Medicine (CBM), Wanfang, CNKI, and CPG-relevant websites were searched from January 2015 to December 2019 by two researchers independently. The RIGHT (Reporting Items for Practice Guidelines in Healthcare) checklist was used to assess the reporting quality in terms of domains and items. Then, a subgroup analysis of the results was performed.Primary and secondary outcome measuresRIGHT checklist reporting rateResultsA total of 66 CPGs were included. Twice as many CPGs were published internationally as were published in China. More than half were updated. Most CPGs are published in journals, developed by societies or associations, and were evidence-based grading. The average reporting rate for all included CPGs was 47.6%. Basic information got the highest (71.7% ± 19.7%) reporting rate, while review and quality assurance got the lowest (22.0% ± 24.6%). Then, a cluster analysis between countries, publishing channels, and institutions was performed. There were no statistically significant differences in the reporting quality on the CPGs between publishing countries (China vs. international), publishing channels (journals vs. websites), and institutions (associations vs. non-associations).ConclusionsCurrent stroke CPGs reports are of low quality. We recommend that guideline developers improve the quality of reporting of key information and improve the management of conflicts of interest. We recommend that guideline developers consider the RIGHT checklist as an important tool for guideline development.Trial registration10.17605/OSF.IO/PBWUX.
A formulation of Clausena anisata (Willd.) Hook. f. Ex Benth and Cassia sieberiana DC. alleviates the symptoms associated with osteoarthritis: a single-blind, randomised controlled trial of a traditional Ghanaian remedy
Authors: Thomford Kwesi Prah , Yorke Joseph , Thomford Ama Kyeraa , Amponsah Isaac Kingsley 
Published: September 2021

Abstract
Background
Clinical validation of herbal medicinal products is important for their widespread acceptance and application. In this single-blind, randomised controlled trial, a traditional Ghanaian herbal medicine formulation with Clausena anisata (Willd.) Hook. f. ex Benth and Cassia sieberiana DC. as ingredients was evaluated for its safety and effectiveness in the management of patients with osteoarthritis. The formulation for the purposes of this study was labelled with the code GC-500.

Methods
A total of 57 participants were randomly assigned to receive either this herbal remedy, GC-500, or the control treatment of diclofenac. Subjects were then followed up for a period of 8 weeks using a modified Graded Chronic Pain Scale (GCPS) for their efficacy assessments. The control treatment comprised 13 subjects and the GC-500 group 44 subjects.

Results
Upon completion of the study, 28 (63.63%) subjects in the GC-500 group attained the primary outcome, (GCPS of Grade 0) compared to 5 (38.46%) subjects in the control group. Improvement in disease indicators such as characteristic pain intensity, disability score and disability days was comparable between the GC-500 and diclofenac. Intensity of pain reduced after 8 weeks of treatment; disability score and disability days also declined indicating an improvement in the quality of life of subjects. GC-500 was also shown to be safe for human use.

Conclusion
The herbal medicine formulation GC-500, provides a credible treatment option for managing the pain associated with osteoarthritis.

Trial registration
This study was retrospectively registered with the Pan-African Trial registry with a Trial ID: PACTR201909643671755 on 25th September, 2019 at https://pactr.samrc.ac.za/Search.aspx
Individual versus general structured feedback to improve agreement in grant peer review: a randomized controlled trial
Authors: Hesselberg Jan-Ole , Fostervold Knut Inge , Ulleberg Pål , Svege Ida 
Published: September 2021

Abstract
Background
Vast sums are distributed based on grant peer review, but studies show that interrater reliability is often low. In this study, we tested the effect of receiving two short individual feedback reports compared to one short general feedback report on the agreement between reviewers.

Methods
A total of 42 reviewers at the Norwegian Foundation Dam were randomly assigned to receive either a general feedback report or an individual feedback report. The general feedback group received one report before the start of the reviews that contained general information about the previous call in which the reviewers participated. In the individual feedback group, the reviewers received two reports, one before the review period (based on the previous call) and one during the period (based on the current call). In the individual feedback group, the reviewers were presented with detailed information on their scoring compared with the review committee as a whole, both before and during the review period. The main outcomes were the proportion of agreement in the eligibility assessment and the average difference in scores between pairs of reviewers assessing the same proposal. The outcomes were measured in 2017 and after the feedback was provided in 2018.

Results
A total of 2398 paired reviews were included in the analysis. There was a significant difference between the two groups in the proportion of absolute agreement on whether the proposal was eligible for the funding programme, with the general feedback group demonstrating a higher rate of agreement. There was no difference between the two groups in terms of the average score difference. However, the agreement regarding the proposal score remained critically low for both groups.

Conclusions
We did not observe changes in proposal score agreement between 2017 and 2018 in reviewers receiving different feedback. The low levels of agreement remain a major concern in grant peer review, and research to identify contributing factors as well as the development and testing of interventions to increase agreement rates are still needed.

Trial registration
The study was preregistered at OSF.io/n4fq3.
Are doctors protected enough during COVID-19 in South Asia?
Authors: Jatoi Nadia Nazir , Ahmad Saniya , Sajid Emad ud-din , Yasmin Farah , Asghar Muhammad Sohaib , Farhan Syed Ali , Sayeed Bushra Zafar , Marufi Momina Mariam , Fatima Kaneez , Mahmood Syed Faisal 
Published: September 2021

Abstract
Background
The highly contagious nature of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) places physicians in South Asia at high risk of contracting the infection. Accordingly, we conducted this study to provide an updated account of physician deaths in South Asia during the COVID-19 pandemic and to analyze and compare the different characteristics associated with physician mortality amongst the countries of the region.

Methods
We performed a cross-sectional study by using published news reports on the websites of news agencies from 9 selected countries in South Asia. Our study included only those physicians and doctors who died after contracting COVID-19 from their respective workplaces. All available data about the country of origin, type of, sex, age, medical or surgical specialty, and date of death were included.

Results
The total number of physician deaths reported due to COVID-19 in our study was 170, with half (87/170, 51%) of the deaths reported from Iran. Male physician deaths were reported to be 145 (145/170 = 85%). Internal Medicine (58.43%) was the most severely affected sub-specialty. The highest physician mortality rate in the general population recorded in Afghanistan (27/1000 deaths). General physicians from India [OR = 11.00(95% CI = 1.06–114.08), p = 0.045] and public sector medical practitioners from Pakistan [aOR = 4.52 (95% CI = 1.18–17.33), p = 0.028] were showing significant mortality when compared with other regions in multivariate logistic regression.

Conclusion
An increased number of physician deaths, owing to COVID-19, has been shown in South Asia. This could be due to decreased personal protective equipment and the poor health care management systems of the countries in the region to combat the pandemic. Future studies should provide detailed information of characteristics associated with physician mortalities along with the main complications arising due to the virus.
Local characterization of the COVID-19 response: the case of a lockdown in Lusaka, Zambia
Authors: Muzyamba Choolwe 
Published: September 2021

Abstract
Background
The onset of the COVID-19 pandemic has sparked heated debate among scholars on the relevance of lockdowns. There are those in favor of the lockdown and others who are critical of it. However, despite the increased interest in understanding the relevance of lockdowns, there still has not been much focus on its relevance in countries like Zambia. Thus, with the help of the Social Representation Theory (SRT), we set out to explore and document the local characterization of the lockdown by residents of Lusaka, Zambia.

Methods
We recruited our participants through convenient and purposive sampling techniques. This was done through the use of the ZAMTEL public phone records. Initial contact was made to potential participants, and they were asked of their availability and willingness to participate in the interview. Upon agreeing to participate, they were included in the sample. A total of 68 people were selected to take part in this study. Their age ranged from 20 to 76 years old. 33 of them were male and 35 females. After this, we conducted interviews with the 68 participants. Due to COVID-19 restrictions, our interviews were conducted via telephone in conformity with the recommendations from the IRB in Lusaka and the advice of the ministry of health. We anonymized the demographic characteristics and responses from our participants. Later, thematic analysis was used to analyze the data.

Results
The lockdown was on one hand lauded for slowing down the incidence rates, preventing fatalities, and protecting the healthcare system from collapse. On the other hand, it was criticized for exacerbating poverty levels, unemployment rates, increasing the rate of mental health problems, aiding gender-based violence, and intensifying political repression and corruption. The results speak to the complexity in the characterization of the lockdown as a response to COVID-19 in Lusaka, Zambia. This observation demonstrates the folly of viewing, applying and characterizing the COVID-19 lockdown as a ‘one-size-fits-all’ approach in Lusaka, Zambia.

Conclusion
Rather than establishing the lockdown as an incontestable good, as it is depicted by some scholars or as useless by its critics, our findings instead demonstrate the diversity and complexity in how it is locally viewed by Lusaka residents. The study provides grounds for caution on simplistic and binary characterization of lockdowns. It indicates the need for careful dialog between the designers of lockdowns and citizens in order to tailor such interventions to local realities in context-specific ways. It also shows that though the development of such interventions, all the various and complex elements it embodies must be taken into account in order to realize optimum outcomes.
Matrix metalloproteinase-1 as a non-invasive biomarker to assess liver fibrosis in children with chronic liver disease
Authors: Behairy Ola Galal , El-Bakry Mohamed Mostafa , Mansour Amira Ibrahim , Abdelrahman Amira M. N. , Emam Ghada Mansour 
Published: September 2021

Abstract
Background
Abnormal extracellular matrix (ECM) turnover is linked to liver fibrosis as it reflects an imbalance between repair and progressive substitution of the liver parenchyma by scar tissue. Matrix metalloproteinases (MMPs) are the primary enzymes involved in ECM breakdown. So, this study aims to measure the value of serum matrix metalloproteinase-1 (MMP-1) in children with chronic liver diseases (CLD) in comparison with liver biopsy and serum biomarkers. A hundred twenty children with chronic liver diseases and sixty healthy children as a control group were included in this study. Both groups were evaluated via medical history, clinical, radiological, laboratory investigations, and serum MMP-1 level was measured by ELISA. Liver biopsy was performed for studied patients only.

Results
The mean MMP-1 was 15.2 ± 5.1 ng/ml in children with CLD, and 64.7 ± 27.4 ng/ml in the control group. MMP-1 was statistically lower in the children with CLD than controls (p < 0.001). The mean ± SD of aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 (FIB-4) scores in all studied cases showed a significant trend of increase with progressive fibrosis stage evident with histological METAVIR scoring system, while serum MMP-1 concentration was decreased significantly with increasing the degree of fibrosis in CLD group (P 0.001). Serum MMP-1 was indirectly correlated with serum biomarkers and the degree of fibrosis in patients.

Conclusions
MMP-1 is a useful non-invasive marker for detection of the stage of liver fibrosis in children with chronic liver diseases.
Magnitude and Temporal Trend of the Chronic Myeloid Leukemia: On the Basis of the Global Burden of Disease Study 2019
Authors: Hu Yuefen , Li Qizhao , Hou Ming , Peng Jun , Yang Xiaorong , Xu Shuqian 
Published: September 2021

PURPOSE To map the magnitudes and temporal trends of chronic myeloid leukemia (CML) along with its attributable risk factors, providing the essential foundation for targeted public policies at the national, regional, and global levels. MATERIALS AND METHODS We retrieved annual data on CML burden in 204 countries and regions from the Global Burden of Disease Study 2019 in 1990-2019. The estimated annual percentage change (EAPC) was calculated to quantify the temporal trends of CML burden by region, sex, and age group. RESULTS Globally, the age-standardized incidence rate of CML declined weakly over the past few years (EAPC: −1.04), but the number of incident cases increased by 54.1% to 65.8 × 103 in 2019. By contrast, a dramatic drop in death and disability-adjusted life years (DALYs) rate (EAPCs: −2.55; −2.69) led to a reduction in deaths and DALYs, especially in high-income regions. In 2019, the highest age-standardized death rate was observed in Ethiopia (1.89 per 100,000). The death rate of CML was pronounced among the population age above 70 years. DALYs of CML worldwide were primarily attributable to smoking (12.2%), high body mass index (5.0%), occupational exposure to benzene (0.9%), and occupational exposure to formaldehyde (0.3%) in 2019. CONCLUSION Although the mortality rate of CML has decreased significantly, the management of patients with CML cannot be neglected, especially in elders and developing regions.
Eye morphogenesis in the blind Mexican cavefish
Authors: Devos Lucie , Agnès François , Edouard Joanne , Simon Victor , Legendre Laurent , El Khallouki Naima , Barbachou Sosthène , Sohm Frédéric , Rétaux Sylvie 
Published: September 2021

ABSTRACT
The morphogenesis of the vertebrate eye consists of a complex choreography of cell movements, tightly coupled to axial regionalization and cell type specification processes. Disturbances in these events can lead to developmental defects and blindness. Here, we have deciphered the sequence of defective events leading to coloboma in the embryonic eye of the blind cavefish of the species Astyanax mexicanus. Using comparative live imaging on targeted enhancer-trap Zic1:hsp70:GFP reporter lines of both the normal, river-dwelling morph and the cave morph of the species, we identified defects in migratory cell behaviours during evagination that participate in the reduced optic vesicle size in cavefish, without proliferation defect. Further, impaired optic cup invagination shifts the relative position of the lens and contributes to coloboma in cavefish. Based on these results, we propose a developmental scenario to explain the cavefish phenotype and discuss developmental constraints to morphological evolution. The cavefish eye appears as an outstanding natural mutant model to study molecular and cellular processes involved in optic region morphogenesis.
Alcohol-Substituted Vinyl Polymers for Stockpiling Hydrogen
Authors: Oka Kouki , Kataoka Miho , Kaiwa Yusuke , Oyaizu Kenichi 
Published: September 2021

Abstract
Hydrogen has a high energy density and produces only water during combustion; consequently, it has attracted considerable attention as a next-generation sustainable energy source. To be used on a daily basis, hydrogen-storage materials need to stockpile hydrogen safely and to release it using only small amounts of energy. Chemically bonded hydrogen stored in a polymer is highly safe, enabling hydrogen to be stored under ambient conditions in a non-volatile, non-toxic, and non-flammable manner. Herein, we report the dehydrogenation reactions of alcohol-substituted vinyl polymers at mild temperatures. Poly(allyl alcohol) was dehydrogenated at 65–95 °C in the presence of an iridium complex catalyst to produce poly(acrylic acid) due to the extremely low activation energy (10 kJ/mol) associated with the catalyst-specific cycle. Poly(allyl alcohol) exhibits a hydrogen-storage density of 6.8 wt% by releasing two equivalents of hydrogen gas, which demonstrates that alcohol-substituted vinyl polymers can be used to stockpile hydrogen and release it under mild conditions.