bluuebunny/crossref_metadata_2025_split huggingface dataset:
The evolving treatment paradigm of advanced hepatocellular carcinoma: putting all the pieces back together
Authors: D’Alessio Antonio , Cammarota Antonella , Prete Maria Giuseppina , Pressiani Tiziana , Rimassa Lorenza 
Published: April 2021

Purpose of review
The therapeutic landscape of advanced hepatocellular carcinoma (HCC) has become notably complex in recent years. With this review, we aimed to put the most recent findings in perspective and tried to delineate the rapidly changing treatment algorithm.

Recent findings
The combination of atezolizumab and bevacizumab has become the new first-line standard of care treatment for unresectable HCC after the positive results of the phase 3 IMbrave150 study. Nivolumab monotherapy failed to demonstrate advantage versus sorafenib in the CheckMate 459 trial, while two different therapeutic strategies (sintilimab and bevacizumab biosimilar and donafenib) outperformed sorafenib in two phase 2/3 studies conducted in the Chinese population. Several immunotherapy combinations are currently under study in large phase 3 trials after promising results in earlier phase studies. About further lines of treatment, the combination of ipilimumab and nivolumab was approved for sorafenib-pretreated patients after the positive results of the phase 1/2 CheckMate 040 study and apatinib was proven effective in the Chinese population in a phase 2/3 study, while pembrolizumab as monotherapy did not show statistically significant superiority when compared with placebo in the KEYNOTE-240 study.

Summary
Because of the growing complexity of advanced HCC treatment, the implementation of predictive biomarkers of response is eagerly needed.
New treatments in advanced gastrointestinal stromal tumor
Authors: Serrano César 
Published: April 2021

Purpose of review
The current article revisits the most recent advances that occurred in the field of gastrointestinal stromal tumor (GIST) therapeutics.

Recent findings
GIST is driven by the oncogenic activation of KIT or PDGFRA receptor tyrosine kinases, and agents targeting these receptors lead to substantial benefit throughout the entire course of the disease. Two new drugs were approved in 2020. On one hand, ripretinib obtained the regulatory approval for the treatment of GIST patients after progression to all standard treatments. On the other hand, avapritinib became the first agent ever displaying activity in GIST driven by the multiresistant PDGFRA D842V mutation. The addition of both drugs to GIST therapeutics constitutes a remarkable milestone, particularly considering that the last agent approved was back in 2012. Similarly, the recent identification of neurotrophic tyrosine receptor kinase (NTRK) fusions in a subset of KIT/PDGFRA wild-type GISTs led to an open window for tailored treatment using specific NTRK inhibitors. Finally, multiple efforts have been made toward the clinical implementation of circulating tumor DNA evaluation to guide clinical decisions in GIST.

Summary
GIST has been consolidated over the years as a paradigmatic model in personalized medicine for the successful development of novel therapeutic strategies through targeted inhibition of oncogenic drivers.
Interventions to Improve Adherence to Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia
Authors: Heiney Sue P. , Sorrell McKenzie , Sheng Jingxi , Adams Swann A. , Nelson Kathy , Nguyen Lan A. , Edwards Amy , Wickersham Karen E. 
Published: April 2021

Background:
Lack of adherence to tyrosine kinase inhibitors (TKIs) is a significant problem resulting in incomplete cytogenetic response and increased mortality in patients with chronic myeloid leukemia (CML). Few studies have been conducted on interventions to improve adherence. The authors conducted a systematic review to explore studies that examined the impact of strategies to improve TKI adherence among individuals with CML.

Methods:
The first 2 authors completed a systematic literature review according to the guidelines in Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). Studies (n=2633) conducted between 1980 and 2019 were identified through 3 databases and examined for inclusion/exclusion criteria.

Results:
Fourteen studies were identified which met the eligibility criteria. The studies only examined adherence to imatinib, dasatinib, or nilotinib. Ten of the 14 used large data sets (commercial health insurance plans or Surveillance Epidemiology and End Results [SEER] data) for analysis. The majority of the studies used a cohort design. Adherence was defined and measured in a variety of ways with most studies using 80% or higher as adequate adherence. Strategies not focused on health care costs used a multidisciplinary team approach.

Conclusion:
Development of evidence to improve treatment adherence to TKIs for CML have relied on large data sets rather than prospective trials. Current studies lack patient focused interventions.
The impact of submucosal fatty tissue during colon endoscopic submucosal dissection in a western center
Authors: Ramos-Zabala Felipe , Parra-Blanco Adolfo , Beg Sabina , Rodríguez-Pascual Jesús , Cárdenas Rebollo José Miguel , Cardozo-Rocabado Rocío , Moreno-Almazán Luis 
Published: April 2021

Objectives
Obesity is associated with submucosal fatty tissue. The main aim of this study was to assess the impact of submucosal fatty tissue on the success of colonic endoscopic submucosal dissection (C-ESD) in a western population.

Methods
This was a retrospective analysis of 125 consecutive C-ESDs performed between October 2015 and July 2017. Fatty tissue sign was defined as positive when the submucosal layer was covered with fatty tissue. The complexity of performing an ESD was assessed by the performing endoscopist, defined by the occurrence of intraprocedural perforation, inability to complete an en-bloc resection or a procedure time exceeding 180 min.

Results
Fatty tissue sign positive was present in 44.8% of the procedures. There were 28 (22.4%) c-ESD defined as complex. Factors associated with complex ESD included; fatty tissue sign [odds ratio (OR) 12.5; 95% confidence interval (CI), 1.9–81.9; P = 0.008], severe fibrosis (OR 148.6; 95% CI, 6.6–3358.0; P = 0.002), poor maneuverability (OR 267.4; 95% CI, 11.5–6212.5; P < 0.001) and polyp size ≥35 mm (OR 17.2; 95% CI, 2.6–113.8; P = 0.003). In patients demonstrating the fatty tissue sign, BMI and waist-to-height ratio (WHtR) were higher (27.8 vs. 24.7; P < 0.001 and 0.56 vs. 0.49; P < 0.001, respectively) and en-bloc resection was achieved less frequently (76.8 vs. 97.1%, P = 0.001). Multivariate analysis revealed higher risk of fatty tissue sign positive associated with WHtR ≥0.52 (OR 26.10, 95% CI, 7.63–89.35, P < 0.001).

Conclusion
This study demonstrates that the fatty tissue sign contributes to procedural complexity during C-ESD. Central obesity correlates with the likelihood of submucosal fatty tissue and as such should be taken into account when planning procedures.
Transjugular intrahepatic portosystemic shunt in refractory ascites: clinical impact of left ventricular diastolic dysfunction
Authors: Debernardi Venon Wilma , Lo Pumo Sara , Imperatrice Barbara , Giorgi Mauro , Righi Dorico , Fonio Paolo , Saracco Giorgio M. , Marzano Alfredo 
Published: April 2021

Background and aims
Left ventricular diastolic dysfunction (LVDD) in cirrhotics are associated with circulatory dysfunction, hepatorenal syndrome (HRS) and heart failure in stressful conditions. Transjugular intrahepatic portosystemic shunt (TIPS) exacerbates the hyperdynamic circulation and challenges cardiac function. We evaluated the incidence and the impact of LVDD in cirrhotic candidates to TIPS for refractory ascites.

Methods
Among 135 patients who underwent TIPS for refractory ascites, 63 cases (child B/C 53/10, Na-model for end-stage liver disease 16.5 ± 0.9) who had 2D-transthoracic-echocardiography with tissue-Doppler-imaging pre-TIPS were retrospectively analysed (group A); in 23 cases cardiac and hormonal assessment before and after TIPS was available. 41 cirrhotics without refractory ascites treated by banding ligation for variceal re-bleeding were used as controls (group B).

Results
The prevalence of LVDD was higher in group A (59%; 22% with grade ≥2) as compared to group B (35%; 7% with grade ≥2) (P < 0.01 and P < 0.03). A lack of clinical response to TIPS occurred in 10 patients, all with LVDD (P < 0.03 vs. no LVDD) and in patients with grade ≥2 LVDD mostly (P < 0.02 vs. grade 1). Central venous pressure >20 mmHg after TIPS and left ventricular end-diastolic volume at basal were predictors of no response to TIPS (P = 0.01 and P = 0.004, respectively), which was an independent predictor of death. Elevated levels of NT-proBNP 3 days after TIPS were associated with advanced cardiac dysfunction (P = 0.005).

Conclusion
NT-proBNP and careful LVDD investigation are useful to better select patients and to predict clinical response and mortality after TIPS.
Small intestinal bacterial overgrowth and orocecal transit time in patients of nonalcoholic fatty liver disease
Authors: Shi Haitao , Mao Lijuan , Wang Lianli , Quan Xiaojing , Xu Xiaoyu , Cheng Yan , Zhu Shanshan , Dai Fei 
Published: April 2021

Objective
The aim of the present study is to explore the frequency of small intestinal bacterial overgrowth (SIBO) and orocecal transit time (OCTT) in patients with nonalcoholic fatty liver disease (NAFLD).

Patients and methods
103 patients with NAFLD and 49 healthy controls were enrolled. Clinical indicators such as BMI, liver function, blood lipids, homeostasis model assessment-insulin resistance (HOMA-IR), serum endotoxin of NAFLD patients were collected and examined. FibroTouch was used to detect the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). SIBO and OCTT were measured by the lactulose hydrogen breath test.

Results
The incidence of SIBO in NAFLD patients (58.3%) was significantly higher than that in healthy controls (26.5%). The level of serum endotoxin in NAFLD patients was higher than that in healthy controls. The levels of CAP, LSM, serum endotoxin, alanine transaminase, asperate aminotransferase and HOMA-IR in SBIO-positive NAFLD patients were higher than those in SIBO-negative patients. There was no significant difference in glutamyl transpeptidase triglyceride, low density lipoprotein and BMI between the two groups. OCTT in NAFLD patients was longer than that in healthy controls. It was also observed that OCTT in SIBO-positive NAFLD patients was significantly delayed compared with SIBO-negative NAFLD patients.

Conclusions
Patients with NAFLD exhibit the increased incidence rate of SIBO and prolonged OCTT; SIBO in NAFLD patients maybe a contributing factor to the elevated transaminase, hepatic steatosis, progression of liver fibrosis and prolonged OCTT.
Utilizing electronic health record data to understand comorbidity burden among people living with HIV: a machine learning approach
Authors: Yang Xueying , Zhang Jiajia , Chen Shujie , Weissman Sharon , Olatosi Bankole , Li Xiaoming 
Published: April 2021

Objectives:
An understanding of the predictors of comorbidity among people living with HIV (PLWH) is critical for effective HIV care management. In this study, we identified predictors of comorbidity burden among PLWH based on machine learning models with electronic health record (EHR) data.

Methods:
The study population are individuals with a HIV diagnosis between January 2005 and December 2016 in South Carolina (SC). The change of comorbidity burden, represented by the Charlson Comorbidity Index (CCI) score, was measured by the score difference between pre- and post-HIV diagnosis, and dichotomized into a binary outcome variable. Thirty-five risk predictors from multiple domains were used to predict the increase in comorbidity burden based on the logistic least absolute shrinkage and selection operator (Lasso) regression analysis using 80% data for model development and 20% data for validation.

Results:
Of 8253 PLWH, the mean value of the CCI score difference was 0.8 ± 1.9 (range from 0 to 21) with 2328 (28.2%) patients showing an increase in CCI score after HIV diagnosis. Top predictors for an increase in CCI score using the LASSO model included older age at HIV diagnosis, positive family history of chronic conditions, tobacco use, longer duration with retention in care, having PEBA insurance, having low recent CD4+ cell count and duration of viral suppression.

Conclusion:
The application of machine learning methods to EHR data could identify important predictors of increased comorbidity burden among PLWH with high accuracy. Results may enhance the understanding of comorbidities and provide the evidence based data for integrated HIV and comorbidity care management of PLWH.
Building a social media-based HIV risk behavior index to inform the prediction of HIV new diagnosis: a feasibility study
Authors: Li Zhenlong , Qiao Shan , Jiang Yuqin , Li Xiaoming 
Published: April 2021

Objective:
Analysis of geolocation-based social media Big Data provides unprecedented opportunities for a broad range of domains including health as health is intrinsically linked to the geographic characteristics of places. HIV infection is largely driven by HIV risk behaviors, such as unsafe sexual behavior and drug abuse/addiction. This study explores the feasibility of building a Social media-based HIV Risk Behavior (SRB) index at the United States county level for informing HIV surveillance and prevention, considering social determinants of health and geographic locations.

Methods:
The SRB index, defined as the proportion of risk behavior related Twitter users among all Twitter users, was calculated at the county level for each year. To evaluate the performance of the new SRB index, the relationships between the county-level SRB and rate of new HIV diagnoses from AIDSVu were analyzed using multivariate regression while simultaneously considering five socioeconomic status (SES) factors (percentage uninsured, median household income, Gini coefficient, percentage living in poverty, percentage high school graduates) in the model. Moran's I and geographically weighted regression analyses (GWR) were leveraged to examine spatial autocorrelations and reveal the potential spatial heterogeneity (geographical variability) of the associations.

Results:
County-level multivariate regression results revealed that SRB has the strongest association with new HIV diagnosis rate (r > 0.36; P < 0.0001) in both years compared with the five SES factors. Hierarchical regression analysis suggested that the SRB index explains significant additional variance in addition to the five SES factors. The results from GWR analysis not only greatly improved the model explanation power (bringing the adjusted r-square from 0.25 to 0.47 in 2016 and 0.26 to 0.55 in 2017) but also revealed SRB index is the most spatially consistent measurement compared with the five SES factors in terms of impact direction (negative or positive correlation).

Conclusion:
It is feasible to build a social media-based HIV risk behavior index (SRB) as a new indicator for HIV surveillance at county level. The SRB index improves the regression model explanation power of new HIV diagnosis by providing additional information beyond the traditional social determinant measures, such as SES indicators. SRB index will allow researchers to utilize data captured within existing social media platforms to better understand the geospatial patterns of HIV risk behavior and to inform population-based HIV surveillance and other efforts of HIV prevention and control.
County-level predictors of retention in care status among people living with HIV in South Carolina from 2010 to 2016: a data-driven approach
Authors: Zeng Chengbo , Zhang Jiajia , Sun Xiaowen , Li Zhenlong , Weissman Sharon , Olatosi Bankole , Li Xiaoming 
Published: April 2021

Objective:
The aim of this study was to examine the geospatial variation of retention in care (RIC) across the counties in South Carolina (SC) from 2010 to 2016 and identify the relevant county-level predictors.

Design:
Aggregated data on county-level RIC among HIV patients from 2010 to 2016 were retrieved from an electronic HIV/AIDS reporting system in SC Department of Health and Environmental Control. Sociological framework of health was used to select potential county-level predictors from multiple public datasets.

Methods:
Geospatial mapping was used to display the spatial heterogeneity of county-level RIC rate in SC. Generalized linear mixed effect regression with least absolute shrinkage and selection operator (LASSO) was employed to identify county-level predictors related to the change of RIC status over time. Confusion matrix and area under the curve statistics were used to evaluate model performance.

Results:
More than half of the counties had their RIC rates lower than the national average. The change of county-level RIC rate from 2010 to 2016 was not significant, and spatial heterogeneity in RIC rate was identified. A total of 22 of the 31 county-level predictors were selected by LASSO for predicting county-level RIC status. Counties with lower collective efficacy, larger proportions of men and/or persons with high education were more likely to have their RIC rates lower than the national average. In contrast, numbers of accessible mental health centres were positively related to county-level RIC status.

Conclusion:
Spatial variation in RIC could be identified, and county-level factors associated with accessible healthcare facilities and social capital significantly contributed to these variations. Structural and individual interventions targeting these factors are needed to improve the county-level RIC and reduce the spatial variation in HIV care.
Adolescent HIV-related behavioural prediction using machine learning: a foundation for precision HIV prevention
Authors: Wang Bo , Liu Feifan , Deveaux Lynette , Ash Arlene , Gosh Samiran , Li Xiaoming , Rundensteiner Elke , Cottrell Lesley , Adderley Richard , Stanton Bonita 
Published: April 2021

Background:
Precision prevention is increasingly important in HIV prevention research to move beyond universal interventions to those tailored for high-risk individuals. The current study was designed to develop machine learning algorithms for predicting adolescent HIV risk behaviours.

Methods:
Comprehensive longitudinal data on adolescent risk behaviours, perceptions, peer and family influence, and neighbourhood risk factors were collected from 2564 grade-10 students at baseline followed for 24 months over 2008–2012. Machine learning techniques [support vector machine (SVM) and random forests] were applied to innovatively leverage longitudinal data for robust HIV risk behaviour prediction. In this study, we focused on two adolescent risk behaviours: had ever had sex and had multiple sex partners. Twenty percent of the data were withheld for model testing.

Results:
The SVM model with cost-sensitive learning achieved the highest sensitivity, at 79.1%, specificity of 75.4% with AUC of 0.86 in predicting multiple sex partners on the training data (10-fold cross-validation), and sensitivity of 79.7%, specificity of 76.5% with AUC of 0.86 on the testing data. The random forest model obtained the best performance in predicting had ever had sex, yielding the sensitivity of 78.5%, specificity of 73.1% with AUC of 0.84 on the training data and sensitivity of 82.7%, specificity of 75.3% with AUC of 0.87 on the testing data.

Conclusion:
Machine learning methods can be used to build effective prediction model(s) to identify adolescents who are likely to engage in HIV risk behaviours. This study builds a foundation for targeted intervention strategies and informs precision prevention efforts in school-setting.
Nutritional Assessment and Associated Factors in Children with Congenital Heart Disease - Ethiopia
Authors: Tesfaye Tigist , Tsega Temesgen , Dessie Azene , Teshome Tesfalem 
Published: April 2021

ABSTRACTWorldwide, congenital heart disease is the principal heart diseases in children and constitutes one of the major causes of infant mortality, particularly in developing countries. Infants and children with congenital heart disease exhibit a range of delays in weight gain and growth. In some instances, the delay can be relatively mild, whereas in other cases, cause the failure to thrive.OBJECTIVESTo determine the nutritional status and associated factors of pediatric patients with congenital heart disease.MATERIAL AND METHODSA cross sectional analytical study was done over a period of 6months (Feb to Jul 2020). A total of 228 subjects with congenital heart disease that come to the cardiac center during the study period where included until the calculated sample size was attained. Data was collected from patient card and care givers of the children included in the study after obtaining their informed consent using data inquiry sheet. Data was then analyzed using Statistical Package for Social Sciences (SPSS) for windows version 25.0. Data is presented using tables and text form. Odds Ratio with 95% Confidence Interval (CI) was used to determine the effect of the independent variables on the outcome variable and P-value less than 0.05 was considered statistically significant.RESULTSA total of 228 children from age 3month to 17yrs with mean age of 4.7 years (SD=3.8 years) were included in the study. Most of the subjects had acyanotic heart disease accounting for 87.7%. The overall prevalence of wasting, underweight and stunting were 41.3%, 49.1% and 43% respectively. Among this children with congenital heart disease those with PAH were found more likely have wasting compared to those without PAH with an odds of 1.9 (95% CI: 1.0-3.4) and also greater chance of being stunted with an odds of 1.9 (95% CI: 1.0-3.4). children above 5years of age were 2.3 times more likely to be underweight.CONCLUSIONMalnutrition is a major problem of patients with CHD. Pulmonary hypertension and older age are associated with increased risk of undernutrition.