bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of prognostic alternative splicing events related to the immune microenvironment of hepatocellular carcinoma
Authors: Yu Shanshan , Cai Luya , Liu Chuan , Gu Ruihong , Cai Lingyi , Zhuo Leying 
Published: April 2021

Abstract
Background
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world, and its 5-year survival rate is less than 20%, despite various treatments being available. Increasing evidence indicates that alternative splicing (AS) plays a nonnegligible role in the formation and development of the tumor microenvironment (TME). However, the comprehensive analysis of the impact on prognostic AS events on immune-related perspectives in HCC is lacking but urgently needed.

Methods
The transcriptional data and clinical information of HCC patients were downloaded from TCGA (The Cancer Genome Atlas) database for calculating immune and stromal scores by ESTIMATE algorithm. We then divided patients into high/low score groups and explored their prognostic significance using Kaplan–Meier curves. Based on stromal and immune scores, differentially expressed AS events (DEASs) were screened and evaluated with functional enrichment analysis. Additionally, a risk score model was established by applying univariate and multivariate Cox regression analyses. Finally, gene set variation analysis (GSVA) was adopted to explore differences in biological behaviors between the high- and low-risk subgroups.

Results
A total of 370 HCC patients with complete and qualified corresponding data were included in the subsequent analysis. According to the results of ESTIMATE analysis, we observed that the high immune/stromal score group had a longer survival probability, which was significantly correlated with prognosis in HCC patients. In addition, 467 stromal/immune score-related DEASs were identified, and enrichment analysis revealed that DEASs were significantly enriched in pathways related to HCC tumorigenesis and the immune microenvironment. More importantly, the final prognostic signature containing 16 DEASs showed powerful predictive ability. Finally, GSVA demonstrated that activation of carcinogenic pathways and immune-related pathways in the high-risk group may lead to poor prognosis.

Conclusions
Collectively, these outcomes revealed prognostic AS events related to carcinogenesis and the immune microenvironment, which may yield new directions for HCC immunotherapy.
Common low complexity regions for SARS-CoV-2 and human proteomes as potential multidirectional risk factor in vaccine development
Authors: Gruca Aleksandra , Ziemska-Legiecka Joanna , Jarnot Patryk , Sarnowska Elzbieta , Sarnowski Tomasz J. , Grynberg Marcin 
Published: April 2021

AbstractBackgroundThe rapid spread of the COVID-19 demands immediate response from the scientific communities. Appropriate countermeasures mean thoughtful and educated choice of viral targets (epitopes). There are several articles that discuss such choices in the SARS-CoV-2 proteome, other focus on phylogenetic traits and history of the Coronaviridae genome/proteome. However none consider viral protein low complexity regions (LCRs). Recently we created the first methods that are able to compare such fragments.ResultsWe show that five low complexity regions (LCRs) in three proteins (nsp3, S and N) encoded by the SARS-CoV-2 genome are highly similar to regions from human proteome. As many as 21 predicted T-cell epitopes and 27 predicted B-cell epitopes overlap with the five SARS-CoV-2 LCRs similar to human proteins. Interestingly, replication proteins encoded in the central part of viral RNA are devoid of LCRs.ConclusionsSimilarity of SARS-CoV-2 LCRs to human proteins may have implications on the ability of the virus to counteract immune defenses. The vaccine targeted LCRs may potentially be ineffective or alternatively lead to autoimmune diseases development. These findings are crucial to the process of selection of new epitopes for drugs or vaccines which should omit such regions.
Low-level variant calling for non-matched samples using a position-based and nucleotide-specific approach
Authors:   NISC Comparative Sequencing Program, Dudley Jeffrey N. , Hong Celine S. , Hawari Marwan A. , Shwetar Jasmine , Sapp Julie C. , Lack Justin , Shiferaw Henoke , Johnston Jennifer J. , Biesecker Leslie G. 
Published: April 2021

Abstract
Background
The widespread use of next-generation sequencing has identified an important role for somatic mosaicism in many diseases. However, detecting low-level mosaic variants from next-generation sequencing data remains challenging.

Results
Here, we present a method for Position-Based Variant Identification (PBVI) that uses empirically-derived distributions of alternate nucleotides from a control dataset. We modeled this approach on 11 segmental overgrowth genes. We show that this method improves detection of single nucleotide mosaic variants of 0.01–0.05 variant allele fraction compared to other low-level variant callers. At depths of 600 × and 1200 ×, we observed > 85% and > 95% sensitivity, respectively. In a cohort of 26 individuals with somatic overgrowth disorders PBVI showed improved signal to noise, identifying pathogenic variants in 17 individuals.

Conclusion
PBVI can facilitate identification of low-level mosaic variants thus increasing the utility of next-generation sequencing data for research and diagnostic purposes.
The experience of Australian general practice patients at high risk of poor health outcomes with telehealth during the COVID-19 pandemic: a qualitative study
Authors: Javanparast Sara , Roeger Leigh , Kwok Yuen , Reed Richard L 
Published: April 2021

Abstract
Background
The emergence of the COVID-19 pandemic has raised concerns about the potential decrease in access and utilisation of general practice services and its impact on patient care. In March 2020, the Australian Government introduced telehealth services to ensure that people more vulnerable to COVID-19 do not delay routine care from their general practitioners. Evidence about patients’ experience of telehealth and its impact on patient care is scarce. This study aimed to investigate the experience with telehealth by Australian general practice patients at high risk of poor health outcomes during the COVID-19 pandemic.

Methods
Semi-structured telephone interviews were conducted with 30 patients from nine general practices in metropolitan Adelaide (May–June 2020). Participants were identified by their regular doctor as being at high risk of poor health outcomes. Interviews sought participants’ perspectives and experiences about telehealth services in the general practice setting during COVID-19, and the value of offering continued telehealth services post pandemic. Interviews were recorded and transcribed verbatim. Data were analysed using a coding structure developed based on deductive codes derived from the research questions and any additional concepts that emerged inductively from interviews.

Results
Participants expressed satisfaction with telehealth including convenient and timely access to general practice services. Yet, participants identified challenges including difficulties in expressing themselves and accessing physical exams. Prescription renewal, discussing test results and simple follow-ups were the most common reasons that telehealth was used. Telehealth was mainly via phone that better suited those with low digital literacy. Participants indicated that an existing doctor-patient relationship was important for telehealth services to be effective. Subjects believed that telehealth services should be continued but needed to be combined with opportunities for face-to-face consultations after the COVID-19 pandemic was over.

Conclusions
The expansion of telehealth supported access to general practice including chronic disease management during the COVID-19 pandemic. In the future, telehealth in Australia is likely to have a stronger place in primary healthcare policy and practice and an increased acceptance amongst patients.
Gastrointestinal symptoms as first remarkable signs of ANCA-associated granulomatosis with polyangiitis: a case report and reviews
Authors: Ledó Nóra , Pethő Ákos Géza 
Published: April 2021

AbstractBackgroundSystemic vasculitis associated with antineutrophil cytoplasmic autoantibodies (ANCA) have an extremely wide variety of symptoms, therefore the fast and proper diagnosis is difficult to establish even for experienced physicians. Gastrointestinal manifestations in ANCA-associated granulomatosis with polyangiitis (GPA) may be present, however, severe, life-threatening complications (such as perforations) are rare.Case presentationA case of an 18-year-old male patient is presented, where gastrointestinal symptoms (abdominal pain, vomiting, diarrhoea) were the first remarkable signs of GPA. The initial diagnosis of inflammatory bowel disease delayed the administration of proper immunosuppressive therapy, which might have contributed to the rare and life-threatening complication of arterial duodenal bleeding with perforation. Our systematic review of the literature found only a few case reports where gastrointestinal symptoms were the first signs of GPA, however, this entity might be more frequent if physicians would think of this possibility more often.ConclusionsGastrointestinal bleeding is a rare but potential lethal complication of vasculitis. Consequently, we recommend investigating the patients diagnosed with GPA for gastrointestinal bleeding during the treatment.
Effect of hookworm infection and anthelmintic treatment on naturally acquired antibody responses against the GMZ2 malaria vaccine candidate and constituent antigens
Authors: Amoani Benjamin , Gyan Ben , Sakyi Samuel Asamoah , Abu Emmanuel Kwasi , Nuvor Samuel Victor , Barnes Precious , Sarkodie-Addo Tracy , Ahenkorah Benjamin , Sewor Christian , Dwomoh Duah , Theisen Michael , Cappello Michael , Wilson Michael D. , Adu Bright 
Published: April 2021

Abstract
Background
Malaria and helminths diseases are co-endemic in most parts of sub-Saharan Africa. Immune responses from each of these pathogens interact, and these interactions may have implications on vaccines. The GMZ2 malaria vaccine candidate is a fusion protein of Plasmodium falciparum merozoite surface protein 3 (MSP3) and glutamate rich protein (GLURP R0). GMZ2 has recently showed modest efficacy in a phase IIb multicenter trial. Here, we assessed the effect of hookworm (Necator americanus) infection and anthelmintic treatment on naturally acquired antibody responses against GMZ2 and constituent antigens.

Methods
This longitudinal cross-sectional study was conducted in the Kintampo North Municipality of Ghana. Blood and stool samples were taken from 158 individuals (4–88 years old) infected with either P. falciparum alone (n = 59) or both hookworm and P. falciparum (n = 63) and uninfected endemic controls (n = 36). Stool hookworm infection was detected by the Kato-Katz method and PCR. Malaria parasitaemia was detected by RDT, light microscopy and P. falciparum-specific 18S rRNA gene PCR. Serum samples were obtained prior to hookworm treatment with a single dose of albendazole (400 mg) and 3 weeks (21 days) after treatment. Levels of IgG1, IgG3 and IgM against GMZ2, MSP3 and GLURP R0 were measured by ELISA and compared among the groups, before and after treatment.

Results
Participants with P. falciparum and hookworm co-infection had significantly higher IgG3 levels to GMZ2 than those with only P. falciparum infection and negative control (p < 0.05) at baseline. Treatment with albendazole led to a significant reduction in IgG3 levels against both GMZ2 and GLURP R0. Similarly, IgM and IgG1 levels against MSP3 also decreased following deworming treatment.

Conclusion
Individuals with co-infection had higher antibody responses to GMZ2 antigen. Treatment of hookworm/malaria co-infection resulted in a reduction in antibody responses against GMZ2 and constituent antigens after albendazole treatment. Thus, hookworm infection and treatment could have a potential implication on malaria vaccine efficacy.
Factors determining ultra-short-term survival and the commencement of active treatment in high-grade serous ovarian cancer: a case comparison study
Authors: Hawarden Amy , Russell Bryn , Gee Mary Ellen , Kayali Fatima , Clamp Andrew , Crosbie Emma Jayne , Edmondson Richard John 
Published: April 2021

Abstract
Background
Despite improvements in median survival some patients with advanced ovarian cancer die within 100 days of diagnosis; the reasons for which remain poorly understood.
Here we investigate if ultra short-term survival can be explained by patient characteristics or treatment pathways.

Methods
A nested case comparison study was used to examine differences between patients with high grade serous ovarian/fallopian tube cancer who died within 100 days (n = 28) compared to a comparison group of patients matched for histology and including any survival greater than 100 days (n = 134).

Results
Cases and comparison patients had similar ages, BMI, ACE-27, deprivation indices, and distribution of disease on CT. There were no significant delays in time to diagnosis or treatment (p = 0.68) between the groups.
However, cases had lower serum albumin, haemoglobin and higher platelet counts than matched comparison patients (p < 0.0001) and a worse performance score (P = 0.006).

Conclusion
Patients who die rapidly after a diagnosis of ovarian cancer are only slightly older and have similar pre treatment frailty compared to patients whose survival approaches the median. However they do appear to undergo greater physiological compromise as a result of their disease.
Combining tissue and circulating tumor DNA increases the detection rate of a CTNNB1 mutation in hepatocellular carcinoma
Authors: Oversoe Stine Karlsen , Clement Michelle Simone , Weber Britta , Grønbæk Henning , Hamilton-Dutoit Stephen Jacques , Sorensen Boe Sandahl , Kelsen Jens 
Published: April 2021

Abstract
Background and aims
Studies suggest that mutations in the CTNNB1 gene are predictive of response to immunotherapy, an emerging therapy for advanced hepatocellular carcinoma (HCC). Analysis of circulating tumor DNA (ctDNA) offers the possibility of serial non-invasive mutational profiling of tumors. Combining tumor tissue and ctDNA analysis may increase the detection rate of mutations.
This study aimed to evaluate the frequency of the CTNNB1 p.T41A mutation in ctDNA and tumor samples from HCC patients and to evaluate the concordance rates between plasma and tissue. We further evaluated changes in ctDNA after various HCC treatment modalities and the impact of the CTNNB1 p.T41A mutation on the clinical course of HCC.

Methods
We used droplet digital PCR to analyze plasma from 95 patients and the corresponding tumor samples from 37 patients during 3 years follow up.

Results
In tumor tissue samples, the mutation rate was 8.1% (3/37). In ctDNA from HCC patients, the CTNNB1 mutation rate was 9.5% (9/95) in the pre-treatment samples. Adding results from plasma analysis to the subgroup of patients with available tissue samples, the mutation detection rate increased to 13.5% (5/37). There was no difference in overall survival according to CTNNB1 mutational status. Serial testing of ctDNA suggested a possible clonal evolution of HCC or arising multicentric tumors with separate genetic profiles in individual patients.

Conclusion
Combining analysis of ctDNA and tumor tissue increased the detection rate of CTNNB1 mutation in HCC patients. A liquid biopsy approach may be useful in a tailored therapy of HCC.
Treatment administered to newborns with congenital syphilis during a penicillin shortage in 2015, Fortaleza, Brazil
Authors: Rocha Ana Fátima Braga , Araújo Maria Alix Leite , Taylor Melanie M. , Kara Edna O. , Broutet Nathalie Jeanne Nicole 
Published: April 2021

Abstract
Background
Between 2014 and 2016, Brazil experienced a severe shortage in penicillin supply, resulting in a lack of treatment among some pregnant women and newborns with syphilis and the use of non-evidence-based regimens. This study evaluated all live births in Fortaleza reported with CS in 2015 in order to identify the different therapeutic regimens used in newborns during this period of penicillin shortage.

Methods
A retrospective cross-sectional study design was conducted using manually extracted data from medical chart review of maternal and infant cases delivered in 2015 from all public maternity hospitals in the city of Fortaleza. Data collection occurred from June 2017 to July 2018.

Results
A total of 575 congenital syphilis cases were reported to the municipality of Fortaleza during 2015 and 469 (81.5%) were analyzed. Of these, only 210 (44.8%) were treated with a nationally-recommended treatment. As alternative therapeutic options, ceftriaxone was used in 65 (13.8%), Cefazolin in 15 (3.2%) and the combination of more than one drug in 179 (38.2%). Newborns with serum VDRL titers ≥1:16 (p = 0.021), who had some clinical manifestation at birth (p = 0.003), who were born premature (p <  0.001), with low birth weight (p = 0.010), with jaundice indicative of the need for phototherapy (p = 0.019) and with hepatomegaly (p = 0.045) were more likely to be treated with penicillin according to national treatment guidelines compared to newborns treated with other regimens.

Conclusion
During the period of shortage of penicillin in Fortaleza, less than half of the infants reported with CS were treated with a nationally-recommended regimen, the remaining received treatment with medications available in the hospital of birth including drugs that are not part of nationally or internationally-recommended treatment recommendations.
Pattern of comorbidities in school-aged children with cerebral palsy in Cross River State, Nigeria
Authors: Duke Roseline E. , Torty Chimaeze , Okorie Uche , Kim Min J. , Eneli Nnena , Edadi Ukam , Burton Kathryn , Tann Cally , Bowman Richard 
Published: April 2021

Abstract
Background
To describe the pattern of comorbidities in school-aged children with cerebral palsy (CP) and to identify which, if any, were associated with poor school attendance.
A cross-sectional study, using the key informant methodology, between December 2017 and July 2018 was conducted in Cross River State, Nigeria. Assessments, confirmation of CP and identification of systemic comorbidities using standard tools and questionnaires were performed. Children confirmed to have CP between the ages 4 to 15 years were included.

Results
Three hundred and eighty-eight children were confirmed to have CP, 59% males. The mean age was 9.2 years ± SD 4.0; 28% were non-ambulatory (gross motor function classification system (GMFCS) level IV-V) and spastic CP was seen in 70%. Comorbidities included Speech impairment 85%, feeding difficulties 86%, and swallowing difficulties 77%, learning difficulties 88%, abnormal behaviour 62%, visual acuity impairment 54%, objective perceptual visual disorders 46%, communication difficulties 45%, epilepsy 35%, hearing impairment 12% and malnutrition 51%. Learning difficulties (OR 10.1, p < 0.001; CI: 3.6–28.1), visual acuity impairment (OR 2.8, p = 0.002; CI: 1.5–5.3), epilepsy (OR 2.3, p = 0.009; CI:1.2–4.3) manual ability classification scale 4–5 (OR 4.7,p = 0.049; CI:1.0–22.2) and CP severity (GMFCS V-VI) OR 6.9 p = 0.002, CI: 2.0–24.0.) were seen as increasing the likelihood of poor school attendance.

Conclusion
Comorbidities were common, and some were associated with limited school attendance. A multidisciplinary tailored approach to care, with application of available therapeutic interventions for comorbidities is suggested. This may be useful in reducing barriers to school attendance.
From income inequality to social inequity: impact on health levels in an international efficiency comparison panel
Authors: Schenkman Simone , Bousquat Aylene 
Published: April 2021

Abstract
Background
Health equity, although addressed in several publications dealing with health efficiency analysis, is not easily translated into the operationalization of variables, mainly due to technical difficulties. Some studies provide evidence that it does not influence health outcomes; others demonstrate that its effect is an indirect one, with the hegemony of material living conditions over its social connotation. The aim of this article is to evaluate the role of health equity in determining health outcomes, in an international comparative analysis of the effectiveness and efficiency of health systems.

Method
Fixed Effects Model Panel and Data Envelopment Analysis, a dynamic and network model, in addition to comparative analysis between methods and health impacts. The effect variables considered in the study were life expectancy at birth and infant mortality, in 2010 and 2015, according to the sociocultural regions of the selected countries. Inequity was assessed both economically and socially. The following dimensions were considered: physical and financial resources, health production (access, coverage and prevention) and intersectoral variables: demographic, socioeconomic, governance and health risks.

Results
Both methods demonstrated that countries with higher inequity levels (regarding income, education and health dimensions), associated or not with poverty, are the least efficient, not reaching the potential for effective health outcomes. The outcome life expectancy at birth exhibited, in the final model, the following variables: social inequity and per capita health expenditure. The outcome infant mortality comprehended the level of education variable, in association with the following healthcare variabels: care seeking due to diarrhea in children under five, births attended by skilled health professionals and the reduction in the incidence of HIV.

Conclusion
The dissociation between the distribution of health outcomes and the overall level of health of the population characterizes a devastating political choice for society, as it is associated with high levels of segregation, disrespect and violence from within. Countries should prioritize health equity, adding value to its resources, since health inequties affect society altogether, generating mistrust and reduced social cohesion.
Reduction of chronic malnutrition for infants in Bogotá, Colombia
Authors: Castro Prieto Paula Andrea , Trujillo Ramírez Kenny Margarita , Moreno Sergio , Holguín Juan Sebastián , Pineda Diana María , Tomasi Simón , Ramirez Varela Andrea 
Published: April 2021

Abstract
Background
According to the 2015 National Survey of the Nutritional Situation in Colombia the prevalence of stunting in children under 5 years of age was 10.8%. In terms of region, Bogotá, presented the highest prevalence rate (13%), a figure that exceeded national records. With the collaboration of local and national government, and nongovernmental it was decided to develop a pilot study involving a public health intervention with residents of Bogotá under 1 year of age with nutritional classification by anthropometry compatible with stunting risk or stunting.

Methods
Pre-experimental, before and after study that sought to determine the magnitude of the change in nutritional status through a 10 months public health nutrition intervention in children under one-year-old residing in 3 prioritized territories of Bogotá.

Results
The intervention comprised 1126 children living in the following territories in Bogotá: Kennedy, San Cristóbal, and Engativá. A total of 43.3% children presented delay in height for age, and 56.7% presented risk of short stature. In the final measurement, data were obtained from 686 children, identifying that 17% of the children progressed from stunting to a stunting risk and that 4.5% recovered their growth trajectory, achieving an adequate length for their age.

Conclusion
That children classified as at risk or stunting at the beginning of the intervention showed an increased probability of approaching or being in the appropriate growth trajectory according to the length-for-age indicator after the intervention.