bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of candidate biomarkers and therapeutic agents for heart failure by bioinformatics analysis
Authors: Kolur Vijayakrishna , Vastrad Basavaraj , Vastrad Chanabasayya , Kotturshetti Shivakumar , Tengli Anandkumar 
Published: July 2021

Abstract
Introduction
Heart failure (HF) is a heterogeneous clinical syndrome and affects millions of people all over the world. HF occurs when the cardiac overload and injury, which is a worldwide complaint. The aim of this study was to screen and verify hub genes involved in developmental HF as well as to explore active drug molecules.

Methods
The expression profiling by high throughput sequencing of GSE141910 dataset was downloaded from the Gene Expression Omnibus (GEO) database, which contained 366 samples, including 200 heart failure samples and 166 non heart failure samples. The raw data was integrated to find differentially expressed genes (DEGs) and were further analyzed with bioinformatics analysis. Gene ontology (GO) and REACTOME enrichment analyses were performed via ToppGene; protein–protein interaction (PPI) networks of the DEGs was constructed based on data from the HiPPIE interactome database; modules analysis was performed; target gene—miRNA regulatory network and target gene—TF regulatory network were constructed and analyzed; hub genes were validated; molecular docking studies was performed.

Results
A total of 881 DEGs, including 442 up regulated genes and 439 down regulated genes were observed. Most of the DEGs were significantly enriched in biological adhesion, extracellular matrix, signaling receptor binding, secretion, intrinsic component of plasma membrane, signaling receptor activity, extracellular matrix organization and neutrophil degranulation. The top hub genes ESR1, PYHIN1, PPP2R2B, LCK, TP63, PCLAF, CFTR, TK1, ECT2 and FKBP5 were identified from the PPI network. Module analysis revealed that HF was associated with adaptive immune system and neutrophil degranulation. The target genes, miRNAs and TFs were identified from the target gene—miRNA regulatory network and target gene—TF regulatory network. Furthermore, receiver operating characteristic (ROC) curve analysis and RT-PCR analysis revealed that ESR1, PYHIN1, PPP2R2B, LCK, TP63, PCLAF, CFTR, TK1, ECT2 and FKBP5 might serve as prognostic, diagnostic biomarkers and therapeutic target for HF. The predicted targets of these active molecules were then confirmed.

Conclusion
The current investigation identified a series of key genes and pathways that might be involved in the progression of HF, providing a new understanding of the underlying molecular mechanisms of HF.
Risk prediction in multicentre studies when there is confounding by cluster or informative cluster size
Authors: Pavlou Menelaos , Ambler Gareth , Omar Rumana Z. 
Published: July 2021

Abstract
Background
Clustered data arise in research when patients are clustered within larger units. Generalised Estimating Equations (GEE) and Generalised Linear Models (GLMM) can be used to provide marginal and cluster-specific inference and predictions, respectively.

Methods
Confounding by Cluster (CBC) and Informative cluster size (ICS) are two complications that may arise when modelling clustered data. CBC can arise when the distribution of a predictor variable (termed ‘exposure’), varies between clusters causing confounding of the exposure-outcome relationship. ICS means that the cluster size conditional on covariates is not independent of the outcome. In both situations, standard GEE and GLMM may provide biased or misleading inference, and modifications have been proposed. However, both CBC and ICS are routinely overlooked in the context of risk prediction, and their impact on the predictive ability of the models has been little explored. We study the effect of CBC and ICS on the predictive ability of risk models for binary outcomes when GEE and GLMM are used. We examine whether two simple approaches to handle CBC and ICS, which involve adjusting for the cluster mean of the exposure and the cluster size, respectively, can improve the accuracy of predictions.

Results
Both CBC and ICS can be viewed as violations of the assumptions in the standard GLMM; the random effects are correlated with exposure for CBC and cluster size for ICS. Based on these principles, we simulated data subject to CBC/ICS. The simulation studies suggested that the predictive ability of models derived from using standard GLMM and GEE ignoring CBC/ICS was affected. Marginal predictions were found to be mis-calibrated. Adjusting for the cluster-mean of the exposure or the cluster size improved calibration, discrimination and the overall predictive accuracy of marginal predictions, by explaining part of the between cluster variability. The presence of CBC/ICS did not affect the accuracy of conditional predictions. We illustrate these concepts using real data from a multicentre study with potential CBC.

Conclusion
Ignoring CBC and ICS when developing prediction models for clustered data can affect the accuracy of marginal predictions. Adjusting for the cluster mean of the exposure or the cluster size can improve the predictive accuracy of marginal predictions.
Community drivers of tuberculosis diagnostic delay in Kampala, Uganda: a retrospective cohort study
Authors: Mercaldo Rachel , Whalen Christopher , Kakaire Robert , Nakkonde Damalie , Handel Andreas , Sekandi Juliet N. 
Published: July 2021

Abstract
Background
Recent approaches to TB control have focused on identifying and treating active cases to halt further transmission. Patients with TB symptoms often delay to seek care, get appropriate diagnosis, and initiate effective treatment. These delays are partly influenced by whom the patients contact within their community network. We aimed to evaluate the community drivers of diagnostic delay in an urban setting in Uganda.

Methods
In this study we analyze data from a retrospective cohort of 194 TB patients in Kampala, Uganda. We characterized the patterns of contacts made by patients seeking care for TB symptoms. The main outcome of interest was total community contact delay, defined as the time patients spent seeking care before visiting a provider capable of diagnosing TB.

Results
Visits to health providers without access to appropriate diagnostic services accounted for 56% of contacts made by cohort members, and were significantly associated with community contact delay, as were symptoms common to other prevalent illnesses, such as bone and joint pain.

Conclusions
Education programs aimed at primary care providers, as well as other community members, may benefit case identification, by informing them of rarer symptoms of TB, potential for co-infections of TB and other prevalent diseases, and the availability of diagnostic services.
Efficacy of two-week therapy with doxycycline-based quadruple regimen versus levofloxacin concomitant regimen for helicobacter pylori infection: a prospective single-center randomized controlled trial
Authors: Alhalabi Marouf , Alassi Mohammed Waleed , Alaa Eddin Kamal , Cheha Khaled 
Published: July 2021

AbstractBackgroundAntibiotic-resistance reduces the efficacy of conventional triple therapy for Helicobacter Pylori infections worldwide, which necessitates using various treatment protocols. We used two protocols, doxycycline-based quadruple regimen and concomitant levofloxacin regimen. The aim was to assess the effectiveness of doxycycline-based quadruple regimen for treating Helicobacter Pylori infections compared with levofloxacin concomitant regimen as empirical first-line therapy based on intention-to-treat (ITT) and per-protocol analyses (PPA) in Syrian population.Settings and designAn open-label, randomised, parallel, superiority clinical trial.MethodsWe randomly assigned 78 naïve patients who tested positive for Helicobacter Pylori gastric infection, with a 1:1 ratio to (D-group) which received (bismuth subsalicylate 524 mg four times daily, doxycycline 100 mg, tinidazole 500 mg, and esomeprazole 20 mg, each twice per day for 2 weeks), or (L-group) which received (levofloxacin 500 mg daily, tinidazole 500 mg, amoxicillin 1000 mg, and esomeprazole 20 mg each twice per day for two weeks). We confirmed Helicobacter Pylori eradication by stool antigen test 8 weeks after completing the treatment.ResultsThirty-nine patients were allocated in each group. In the D-group, 38 patients completed the follow-up, 30 patients were cured. While in the L-group, 39 completed the follow-up, 32patients were cured. According to ITT, the eradication rates were 76.92%, and 82.05%, for the D-group and L-group respectively. Odds ratio with 95% confidence interval was 1.371 [0.454–4.146]. According to PPA, the eradication rates were 78.9%, and 82.05% for the D-group and L-group respectively. The odds ratio with 95% confidence interval was 1.219 [0.394–3.774]. We didn’t report serious adverse effects.ConclusionsLevofloxacin concomitant therapy wasn’t superior to doxycycline based quadruple therapy. Further researches are required to identify the optimal first-line treatment for Helicobacter-Pylori Infection in the Syrian population.Trial registrationWe registered this study as a standard randomized clinical trial (Clinicaltrial.gov, identifier-NCT04348786, date:29-January-2020).
Reductions in AFP and PIVKA-II can predict the efficiency of anti-PD-1 immunotherapy in HCC patients
Authors: Sun Xuqi , Mei Jie , Lin Wenping , Yang Ziliang , Peng Wei , Chen Jinbin , Zhang Yaojun , Xu Li , Chen Minshan 
Published: July 2021

Abstract
Background
Few biomarkers can predict the efficiency of PD-1 blockade in patients with hepatocellular carcinoma (HCC). This study aimed to investigate the prognostic role of AFP and PIVKA-II in HCC patients receiving anti-PD-1 immunotherapy.

Methods
A total of 235 HCC patients treated with PD-1 blockade were enrolled. Serum AFP and PIVKA-II levels were collected before and after treatments. The patients were divided into groups based on the reduction in AFP and PIVKA-II: AFP reduction ≤50% vs AFP reduction > 50% and PIVKA-II reduction ≤50% vs PIVKA-II reduction > 50%. The primary endpoints included objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Binary logistic regression analyses were used to explore the related factors of ORR. A Cox proportional hazards model was employed to identify the potential prognostic factors of PFS and OS.

Results
Among all the patients, 34.9% (82/235) achieved a complete or partial response. There was a positive correlation between AFP reduction > 50% or PIVKA-II reduction> 50% and the ORR of PD-1 blockade (P < 0.001 and = 0.003). PFS was significantly improved in patients with AFP reduction > 50% and PIVKA-II reduction > 50% (p < 0.001 and = 0.021). In addition, AFP reduction > 50% and PIVKA-II reduction> 50% were positively correlated with longer OS (p = 0.003 and 0.006).

Conclusion
Early reductions in AFP and PIVKA-II can be predictors of the efficacy of PD-1 blockade in HCC patients.
Treatment optimization of pelvic external beam radiation and/or vaginal brachytherapy for patients with stage I to II high-risk Endometrioid adenocarcinoma: a retrospective multi-institutional analysis
Authors: Wang Wenhui , Zou Lijuan , Wang Tiejun , Liu Zi , He Jianli , Sun Xiaoge , Zhong Wei , Zhao Fengju , Li Xiaomei , Li Sha , Zhu Hong , Ma Zhanshu , Sun Shuai , Jin Meng , Zhang Fuquan , Hou Xiaorong , Wei Lichun , Hu Ke 
Published: July 2021

Abstract
Background
For stage I to II high-risk endometrioid adenocarcinoma patients, the optimal adjuvant radiotherapy modality remains controversial. The present study sought to optimize the treatment of pelvic external beam radiation (EBRT) with/or vaginal brachytherapy (VBT) for high-risk endometrioid adenocarcinoma patients in multiple radiation oncology centers across China.

Methods
This article retrospectively reviewed stage I to II patients with resected endometrioid adenocarcinoma treated at 13 radiation centers from 1999 to 2015. Patients were eligible if they had high-risk features (stage IB Grade 3 disease or stage II Grade 1–3 disease) on the basis of ESMO-ESGO-ESTRO risk group consensus.

Results
A total of 218 patients were included. Fifty-one patients received EBRT, 25 patients received VBT, and 142 patients were administered EBRT combined with VBT. The three groups were comparable in baseline characteristics, except the proportion of stage IB and Grade 3 disease in the VBT group was significantly higher and their age was older. Survival analysis showed that OS, DFS, LRFS and DMFS were significantly different among the three groups. Two out of three groups were compared with each other, and results demonstrated that DFS, LRFS and DMFS were worse in the VBT group than in the EBRT or EBRT + VBT group. The 3-year OS rates were 95.2, 85.2 and 95.1% in the EBRT, VBT and EBRT + VBT groups, respectively (p = 0.043). There was no significant difference in survival outcomes between EBRT group and EBRT + VBT group. A propensity matching analysis was performed to eliminate group differences. The results demonstrated that DFS and LRFS were significantly improved in the pelvic radiation group compared to the VBT group. Distant failure accounted for most of the failure patterns. Patients in the VBT group had significantly increased local and regional recurrence rates than patients in the EBRT or EBRT + VBT group. Acute and chronic radiation-induced toxicities were well tolerated for all patients.

Conclusion
For patients with postoperative stage I to II high-risk endometrioid adenocarcinoma, compared with VBT alone, radiotherapy modalities including EBRT significantly improved DFS, LRFS and DMFS with tolerable adverse effects. Overall survival was not significantly different between EBRT and EBRT + VBT modalities.
The disposable bandage soft contact lenses therapy and anterior segment optical coherence tomography for management of ocular graft-versus-host disease
Authors: Sun Yi-Chen , Inamoto Yoshihiro , Wang Ruikang K. , Lee Stephanie J. , Hung Kai-Feng , Shen Tueng T. 
Published: July 2021

Abstract
Purpose
To identify the ocular surface changes of ocular graft-versus-host disease (GVHD) using anterior segment optical coherence tomography (AS-OCT) and examine the efficacy of disposable bandage soft contact lens (BSCL) treatment in ocular GVHD patients.

Methods
This study is a prospective, Phase II clinical trial. Nineteen patients diagnosed with chronic GVHD based on the NIH criteria and ocular symptoms of NIH eye score 2 or greater were enrolled. Disposable BSCL was applied to the GVHD-affected eyes with topical antibiotic coverage. Ocular exams, eye symptom surveys, and AS-OCT were performed with signed informed consent. Patients were followed for one to three months.

Results
Thirty-eight eyes of 19 patients with ocular GVHD underwent BSCL treatment in this study. AS-OCT scans were done in 14 out of 19 patients. The mean best-corrected visual acuity at enrollment, 2-week, and 4-week visits was 0.180, 0.128, and 0.163 logMAR, respectively. Twenty-four out of 25 eyes (96 %) that initially presented with conjunctival inflammation, twenty-three out of 30 eyes (76.7 %) that initially presented with punctate epithelial erosion, and 8 out of 15 (53.3 %) eyes that initially presented with filamentous keratopathy showed improvement after wearing BSCL for 2 to 4 weeks. AS-OCT revealed corneal epithelial irregularity, abnormal meibomian gland orifice, and conjunctival hyperemia, in patients with ocular GVHD.

Conclusions
BSCL treatment provided significant subjective and objective improvements in ocular GVHD patients. Meanwhile, we found that AS-OCT can be a promising diagnostic tool to characterize the ocular surface changes associated with ocular GVHD.
Could age increase the strength of inverse association between ultraviolet B exposure and colorectal cancer?
Authors: Purushothaman Vidya Lakshmi , Cuomo Raphael E. , Garland Cedric F. , Mackey Timothy K. 
Published: July 2021

Abstract
Background
Vitamin D has been identified as a potential protective factor in the development of colorectal cancer (CRC). We expect to see a stronger association of ultraviolet B (UVB) exposure and CRC crude rates with increasing age since chronic vitamin D deficiency leads to sustained molecular changes that increase cancer risk. The DINOMIT (disjunction, initiation, natural selection, overgrowth, metastasis, involution, and transition) model postulates various stages of cancer development due to vitamin D deficiency and the associated latency period. The purpose of this study is to examine this age-dependent inverse relationship globally.

Methods
In this ecological study, a series of linear and polynomial regression tests were performed between country-specific UVB estimates adjusted for cloud cover and crude incidence rates of CRC for different age groups. Multiple linear regression was used to investigate the association between crude incidence rates of colorectal cancer and UVB estimate adjusting for urbanization, skin pigmentation, smoking, animal consumption, per capita GDP, and life expectancy. Statistical analysis was followed by geospatial visualization by producing choropleth maps.

Results
The inverse relationship between UVB exposure and CRC crude rates was stronger in older age groups at the country level. Quadratic curve fitting was preferred, and these models were statistically significant for all age groups. The inverse association between crude incidence rates of CRC and UVB exposure was statistically significant for age groups above 45 years, after controlling for covariates.

Conclusion
The age-dependent inverse association between UVB exposure and incidence of colorectal cancer exhibits a greater effect size among older age groups in global analyses. Studying the effect of chronic vitamin D deficiency on colorectal cancer etiology will help in understanding the necessity for population-wide screening programs for vitamin D deficiency, especially in regions with inadequate UVB exposure. Further studies are required to assess the need for adequate public health programs such as selective supplementation and food fortification.
Factors associated with the intention of Syrian adult population to accept COVID19 vaccination: a cross-sectional study
Authors: Mohamad Okbah , Zamlout Ali , AlKhoury Naseem , Mazloum Abd Aljawad , Alsalkini Marah , Shaaban Rafea 
Published: July 2021

Abstract
Background and objectives
With global efforts to develop and deliver a COVID-19 vaccine rapidly, vaccine hesitancy stands as a barrier to these efforts. We aimed to estimate the proportion of Syrian adult population intending to be vaccinated against COVID-19 and, principally, to assess the demographic and attitudinal factors associated with it in order to approach suitable solutions.

Methods
An anonymous online questionnaire was conducted between 23rd December 2020 and 5th January 2021 in various provinces in Syria. A total of 3402 adults were sampled to reflect the population demographic factors. Attitudinal factors included Covid-19 fears, risks, and beliefs on the origin. Vaccination hesitancy and knowledge were also measured. The intention to get vaccinated against COVID-19 was the primary endpoint.

Results
According to their statements, 1222 participants (35.92%) will consent to get vaccinated against COVID-19. Our findings indicate that male gender, younger age, rural residence, not having children, smoking, fear about COVID-19, individual perceived severity, believing in the natural origin of the coronavirus, and high vaccination knowledge were positive predictors of embracing COVID-19 vaccine when it is available.

Conclusion
COVID-19 vaccine acceptance rate is considerably poor across Syrian population compared to populations in developed countries. Vaccine hesitancy is closely bound to the fear of side effects and doubts about vaccine efficacy. Factors such as conspiracy beliefs and myths about the vaccine lower vaccine uptake. Thus, interventional educational campaigns are increasingly required to overcome misinformation and avert low vaccination acceptance rates.
Understanding and managing HIV infection risk among men who have sex with men in rural Uganda: a qualitative study
Authors: Nakiganda Lydia Jacenta , Bell Stephen , Grulich Andrew E. , Serwadda David , Nakubulwa Rosette , Poynten Isobel Mary , Bavinton Benjamin R. 
Published: July 2021

Abstract
Background
Same-sex sexual relations are criminalised in Uganda, and men who have sex with men (MSM) experience a high burden of HIV infection. In Uganda, health promotion policies focus on equity in healthcare and creating enabling environments. At present there is limited evidence upon which to enhance engagement of MSM in rural settings into effective HIV prevention. To fill this gap, our study explored MSM’s understandings of HIV risk and strategies used to reduce HIV risk in their sexual lives.

Methods
In-depth interviews were conducted with sixteen MSM in rural communities in Southwestern Uganda. Inductive thematic analysis examined men’s perceptions of HIV risk and strategies of reducing their own HIV risks.

Results
Understandings of HIV risk and risk practices were framed by lack of access to condoms, challenges negotiating condom and pre-exposure prophylaxis (PrEP) use, and condomless sex being reported as more pleasurable than sex with condoms. Strategies men perceived as enabling them to manage HIV risk included: PrEP use; condom use; knowing partners’ HIV status; avoiding partners associated with HIV risk; oral sex; withdrawal before ejaculation and washing one’s penis after sex. There were several misconceptions arising from poor HIV prevention knowledge. Strategies reliant on communication and negotiation with sexual partners were inhibited by gendered powered imbalances.

Conclusions
Our findings illustrate that MSM in rural settings in Uganda are making concerted efforts to implement strategies that might reduce risk of HIV transmission and infection within their sexual relationships. Key HIV health promotion and service-related strategies to support MSM with these efforts include an effective condom and lubricant supply chain; a PrEP program in trusted local health units, implemented via discreet community-outreach mechanisms; and same-sex specific HIV-related health promotion.
Potentials of community-based early detection of cardiovascular disease risk during the COVID-19 pandemic
Authors: Siregar Kemal Nazarudin , Kurniawan Rico , BaharuddinNur Ryza Jazid , Nuridzin Dion Zein , Handayani Yolanda , Retnowati  , Rohjayanti  , Halim Lindawati 
Published: July 2021

Abstract
Background
The Coronavirus Disease 2019 (COVID-19) pandemic has led to a significant decline in Non Communicable Diseases (NCD) screening and early detection activities, especially Cardiovascular Disease (CVD). This study aims to assess the potential of community-based self-screening of CVD risk through the mhealth application.

Methods
This is operational research by actively involving the community to carry out self-screening through the mHealth application. Community health workers were recruited as facilitators who encourage the community to carry out self-screening. To evaluate the potential of community-based self-screening of CVD risk, we use several indicators: responses rate, level of CVD risk, and community acceptance.

Results
Of the 846 individuals reached by the cadres, 53% or 442 individuals carried out self-screening. Based on the results of self-screening of CVD risk, it is known that around 21.3% are at high risk of developing CVD in the next 10 years. The results of the evaluation of semi-structured questions showed that about 48% of the people had positive impressions, 22% assessed that this self-screening could increase awareness and was informative, 3% suggested improvements to self-screening tools.

Conclusion
Cadres play an important role in reaching and facilitating the community in their environment to remain aware of their health conditions by conducting self-screening of CVD risk. The availability of the mHealth application that the public can easily access can simplify CVD risk prediction and expand screening coverage, especially during the COVID-19 pandemic, where there are social restrictions policies and community activities.