bluuebunny/crossref_metadata_2025_split huggingface dataset:
Translation, transcultural adaptation and validation to Brazilian Portuguese of tools for adverse drug reaction assessment in children
Authors: da Costa Lima Elisangela , de Barros Fernandes Thais , Freitas Adair , de Lima Sias Juliana Freire , Land Marcelo Gerardin Poirot , Aires Mariana Tschoepke , Bracken Louise , Peak Matthew 
Published: July 2021

Abstract
Background
Children are more vulnerable to adverse drug reactions (ADRs) due to complex changes in the body during the growth process and lack specific pharmacoepidemiologic studies. Causality and Avoidability assessment of ADRs are relevant to clinical guidelines development and pharmacovigilance. This study aimed to translate and transcultural adapt two new tools—Liverpool Causality Assessment Tool (LCAT) and the Liverpool Avoidability Assessment Tool (LAAT)—to Brazilian-Portuguese and evaluate the psychometric properties of these tools to analyse ADRs in Brazilian children.

Methods
The validation of the cross-cultural adaptation of tools was obtained by the functional (conceptual, semantic, operational, and measurement) equivalence between the original and translated versions of each instrument. The translated version of LCAT and LAAT was applied to assessing the twenty-six case reports of suspected adverse drug reactions in a Brazilian teaching paediatric hospital. The inter-rater reliability (a pharmacist and a physician) was evaluated using Cronbach’s alpha. The exact agreement percentages (%EA) and extreme disagreement (%ED) were computed. Overall Kappa index was calculated with a 95% confidence interval.

Results
There was a need to modify some terms translated into Portuguese for semantic and conceptual equivalence. The Cronbach’s alpha coefficient values obtained were 0.95 and 0.85, and the weighted Kappa (95% confidence interval) were 0.82 (0.67–0.97) and 0.68 (0.45–0.91) for LCAT and LAAT, respectively. The Brazilian-Portuguese versions of the LCAT and LAAT showed reliable and valid tools for the diagnosis and follow-up of ADRs in children.

Conclusion
The methodological approach allowed the translation, transcultural adaptation, and validation to Brazilian-Portuguese of two easy and quick to perform tools for causality and avoidability of ADRs in children by a multidisciplinary expert specialist committee, including the authors of original tools. We believe these versions may be applied by professionals (patient safety teams) and researchers in Brazil in groups or by a single reviewer.

Trial registration
This study was evaluated and approved by the Research Ethics Committee (Instituto de Pediatria e Puericultura Martagão Gesteira – Federal University of Rio de Janeiro – Number: 3.264.238.
Symptoms and signs of colorectal cancer, with differences between proximal and distal colon cancer: a prospective cohort study of diagnostic accuracy in primary care
Authors: Holtedahl Knut , Borgquist Lars , Donker Gé A. , Buntinx Frank , Weller David , Campbell Christine , Månsson Jörgen , Hammersley Victoria , Braaten Tonje , Parajuli Ranjan 
Published: July 2021

Abstract
Background
In an abdominal symptom study in primary care in six European countries, 511 cases of cancer were recorded prospectively among 61,802 patients 16 years and older in Norway, Denmark, Sweden, Netherlands, Belgium and Scotland. Colorectal cancer is one of the main types of cancer associated with abdominal symptoms; hence, an in-depth subgroup analysis of the 94 colorectal cancers was carried out in order to study variation in symptom presentation among cancers in different anatomical locations.

Method
Initial data capture was by completion of standardised forms containing closed questions about symptoms recorded during the consultation. Follow-up data were provided by the GP after diagnosis, based on medical record data made after the consultation. GPs also provided free text comments about the diagnostic procedure for individual patients. Fisher’s exact test was used to analyse differences between groups.

Results
Almost all symptoms recorded could indicate colorectal cancer. ‘Rectal bleeding’ had a specificity of 99.4% and a PPV of 4.0%. Faecal occult blood in stool (FOBT) or anaemia may indicate gastrointestinal bleeding: when these symptoms and signs were combined, sensitivity reached 57.5%, with 69.2% for cancer in the distal colon. For proximal colon cancers, none of 18 patients had ‘Rectal bleeding’ at the initial consultation, but three of the 18 did so at a later consultation. ‘Abdominal pain, lower part’, ‘Constipation’ and ‘Distended abdomen, bloating’ were less specific and also less sensitive than ‘Rectal bleeding’, and with PPV between 0.7% and 1.9%.

Conclusions
Apart from rectal bleeding, single symptoms did not reach the PPV 3% NICE threshold. However, supplementary information such as a positive FOBT or persistent symptoms may revise the PPV upwards. If a colorectal cancer is suspected by the GP despite few symptoms, the total clinical picture may still reach the NICE PPV threshold of 3% and justify a specific referral.
Daily, oral FMT for long-term maintenance therapy in ulcerative colitis: results of a single-center, prospective, randomized pilot study
Authors: Crothers Jessica W. , Chu Nathaniel D. , Nguyen Le Thanh Tu , Phillips Magen , Collins Cheryl , Fortner Karen , Del Rio-Guerra Roxana , Lavoie Brigitte , Callas Peter , Velez Mario , Cohn Aaron , Elliott Ryan J. , Wong Wing Fei , Vo Elaine , Wilcox Rebecca , Smith Mark , Kassam Zain , Budd Ralph , Alm Eric J. , Mawe Gary M. , Moses Peter L. 
Published: July 2021

Abstract
Background
Fecal microbiota transplantation (FMT) is a promising new strategy in the treatment of Inflammatory Bowel Disease, but long-term delivery systems are lacking. This randomized study was designed as a safety and feasibility study of long-term FMT in subjects with mild to moderate UC using frozen, encapsulated oral FMT (cFMT).

Methods
Subjects were randomized 1:1 to receive FMT induction by colonoscopy, followed by 12 weeks of daily oral administration of frozen encapsulated cFMT or sham therpay. Subjects were followed for 36 weeks and longitudenal clinical assessments included multiple subjective and objective markers of disease severity. Ribosomal 16S bacterial sequencing was used to assess donor-induced changes in the gut microbiota. Changes in T regulatory (Treg) and mucosal associated invariant T (MAIT) cell populations were evaluated by flow cytometry as an exploratory endpoint.

Results
Twelve subjects with active UC were randomized: 6 subjects completed the full 12-week course of FMT plus cFMT, and 6 subjects received sham treatment by colonic installation and longitudinal oral placebo capules. Chronic administration of cFMT was found to be safe and well-tolerated but home storage concerns exist. Protocol adherence was high, and none of the study subjects experienced FMT-associated treatment emergent adverse events. Two subjects that received cFMT achieved clinical remission versus none in the placebo group (95% CI = 0.38-infinity, p = 0.45). cFMT was associated with sustained donor-induced shifts in fecal microbial composition. Changes in MAIT cell cytokine production were observed in cFMT recipients and correlated with treatment response.

Conclusion
These pilot data suggest that daily encapsulated cFMT may extend the durability of index FMT-induced changes in gut bacterial community structure and that an association between MAIT cell cytokine production and clinical response to FMT may exist in UC populations. Oral frozen encapsulated cFMT is a promising FMT delivery system and may be preferred for longterm treatment strategies in UC and other chronic diseases but further evaluations will have to address home storage concerns. Larger trials should be done to explore the benefits of cFMT and to determine its long-term impacts on the colonic microbiome. Trial registration: ClinicalTrials.gov (NCT02390726). Registered 17 March 2015, https://clinicaltrials.gov/ct2/show/NCT02390726?term=NCT02390726&draw=2&rank=1.
Lung abscess secondary to lung cancer with a coinfection of Granulicatellaadiacens and other bacteria: a case report
Authors: Yang Shuo , Wu Liangliang , Xu Lili , Huang Xiang , Sun Xiaofeng , Yang Lan , Xu Ling 
Published: July 2021

Abstract
Background
Granulicatella adiacens is facultative anaerobic Gram-positive bacteria, which mainly involve bacterial endocarditis and bacteremia, but there are few reports of local suppurative infection. A case of lung abscess with a coinfection of Granulicatella adiacens and other bacteria in a lung cancer patient will be reported in this paper. To our knowledge, this is the first case report describing lung abscess due to G.adiacens.

Case presentation
A 52-year-old Chinese woman was admitted to the hospital, She complained of coughing and expectoration for 1 month, shortness of breath for half a month, and dyspnea for 1 day. After a series of examinations, she was diagnosed with lung abscess, pleural effusion, and bronchogenic carcinoma. Draining pus culture demonstrated Granulicatella adiacens. After more than 5 weeks of antibiotic therapies in total, she gradually recovered to fight against lung cancer.

Conclusion
This is the first reported lung abscess caused by G.adiacens. In immunosuppressed hosts, G.adiacens is a virulent pathogen associated with a spectrum of intrathoracic suppurative. Earlier diagnosis and proper drainage surgery with effective antibiotics treatment are very important, and antimicrobial treatment should be more than 5 weeks. When complex pulmonary infection interferes with the CT diagnosis, clinical suspicion of lung cancer should be increased if G.adiacens or Eikenella corrodens is detected from a pulmonary infection.
Predictors of mortality in patients with coronavirus disease 2019: a systematic review and meta-analysis
Authors: Shi Changcheng , Wang Limin , Ye Jian , Gu Zhichun , Wang Shuying , Xia Junbo , Xie Yaping , Li Qingyu , Xu Renjie , Lin Nengming 
Published: July 2021

Abstract
Background
Coronavirus disease 2019 (COVID-19) is associated with a high mortality rate, especially in patients with severe illness. We conducted a systematic review and meta-analysis to assess the potential predictors of mortality in patients with COVID-19.

Methods
PubMed, EMBASE, the Cochrane Library, and three electronic Chinese databases were searched from December 1, 2019 to April 29, 2020. Eligible studies reporting potential predictors of mortality in patients with COVID-19 were identified. Unadjusted prognostic effect estimates were pooled using the random-effects model if data from at least two studies were available. Adjusted prognostic effect estimates were presented by qualitative analysis.

Results
Thirty-six observational studies were identified, of which 27 were included in the meta-analysis. A total of 106 potential risk factors were tested, and the following important predictors were associated with mortality: advanced age, male sex, current smoking status, preexisting comorbidities (especially chronic kidney, respiratory, and cardio-cerebrovascular diseases), symptoms of dyspnea, complications during hospitalization, corticosteroid therapy and a severe condition. Additionally, a series of abnormal laboratory biomarkers of hematologic parameters, hepatorenal function, inflammation, coagulation, and cardiovascular injury were also associated with fatal outcome.

Conclusion
We identified predictors of mortality in patients with COVID-19. These findings could help healthcare providers take appropriate measures and improve clinical outcomes in such patients.
Community based screening for sickle haemoglobin among pregnant women in Benue State, Nigeria: I-Care-to-Know, a Healthy Beginning Initiative
Authors: Ezenwosu Osita U. , Itanyi Ijeoma U. , Nnodu Obiageli E. , Ogidi Amaka G. , Mgbeahurike Fabian , Ezeanolue Echezona E. 
Published: July 2021

Abstract
Background
Haemoglobin genotype screening at prenatal care offers women an opportunity to be aware of their genotype, receive education on sickle cell disease (SCD) and may increase maternal demand for SCD newborn screening. In developed countries, most pregnant women who access prenatal care and deliver at the hospital receive haemoglobin genotype screening. In settings with low prenatal care attendance and low hospital deliveries, community-based screening may provide similar opportunity for pregnant women. We assessed the feasibility and acceptability of integrating haemoglobin genotype screening into an existing community-based HIV program.

Methods
Onsite community-based integrated testing for HIV, hepatitis B virus and haemoglobin electrophoresis, were conducted for pregnant women and their male partners. Community Health Advisors implementing the NIH and PEPFAR-supported Healthy Beginning Initiative (HBI) program provided education on SCD, collected blood sample for haemoglobin electrophoresis and provided test results to participants enrolled into the HBI program. We concurrently conducted a cross-sectional study using a pretested, semi-structured, interviewer administered questionnaire to collect demographic data and assess awareness of individual haemoglobin “genotype” among HBI pregnant women participants.

Results
In this study, 99.9% (10,167/10,168) of pregnant women who received education on SCD accepted and completed the survey, had blood drawn for haemoglobin electrophoresis and received their results. A majority of participating pregnant women (97.0%) were not aware of their haemoglobin “genotype”. Among the participants who were incorrect about their haemoglobin “genotype”, 41.1% (23/56) of women who reported their haemoglobin “genotype” as AA were actually AS. The odds of haemoglobin “genotype” awareness was higher among participants who were in younger age group, completed tertiary education, had less number of pregnancies, and attended antenatal care. Overall prevalence of sickle cell trait (AS) was 18.7%.

Conclusions
It is feasible to integrate haemoglobin “genotype” testing into an existing community-based maternal-child program. Most pregnant women who were unaware of their haemoglobin “genotype” accepted and had haemoglobin genotype testing, and received their test results. Increasing parental awareness of their own haemoglobin “genotype” could increase their likelihood of accepting newborn screening for SCD.
Genetic expression and mutational profile analysis in different pathologic stages of hepatocellular carcinoma patients
Authors: Gao Xingjie , Zhao Chunyan , Zhang Nan , Cui Xiaoteng , Ren Yuanyuan , Su Chao , Wu Shaoyuan , Yao Zhi , Yang Jie 
Published: July 2021

Abstract
Background
The clinical pathologic stages (stage I, II, III-IV) of hepatocellular carcinoma (HCC) are closely linked to the clinical prognosis of patients. This study aims at investigating the gene expression and mutational profile in different clinical pathologic stages of HCC.

Methods
Based on the TCGA-LIHC cohort, we utilized a series of analytical approaches, such as statistical analysis, random forest, decision tree, principal component analysis (PCA), to identify the differential gene expression and mutational profiles. The expression patterns of several targeting genes were also verified by analyzing the Chinese HLivH060PG02 HCC cohort, several GEO datasets, HPA database, and diethylnitrosamine-induced HCC mouse model.

Results
We identified a series of targeting genes with copy number variation, which is statistically associated with gene expression. Non-synonymous mutations mainly existed in some genes (e.g.,TTN, TP53, CTNNB1). Nevertheless, no association between gene mutation frequency and pathologic stage distribution was detected. The random forest and decision tree modeling analysis data showed a group of genes related to different HCC pathologic stages, including GAS2L3 and SEMA3F. Additionally, our PCA data indicated several genes associated with different pathologic stages, including SNRPA and SNRPD2. Compared with adjacent normal tissues, we observed a highly expressed level of GAS2L3, SNRPA, and SNRPD2 (P = 0.002) genes in HCC tissues of our HLivH060PG02 cohort. We also detected the high expression pattern of GAS2L3, SEMA3F, SNRPA, and SNRPD2 in the datasets of GSE102079, GSE76427, GSE64041, GSE121248, GSE84005, and the qPCR assay using diethylnitrosamine-induced HCC mouse model. Moreover, SEMA3F and SNRPD2 protein were highly stained in the HCC tissues of the HPA database. The high expression level of these four genes was associated with the poor survival prognosis of HCC cases.

Conclusions
Our study provides evidence regarding the gene expression and mutational profile in different clinical pathologic stages of TCGA HCC cases. Identifying four targeting genes, including GAS2L3, SNRPA, SNRPD2, and SEMA3F, offers insight into the molecular mechanisms associated with different prognoses of HCC.
The correlation of next-generation sequencing-based genotypic profiles with clinicopathologic characteristics in NPM1-mutated acute myeloid leukemia
Authors: Wang Biao , Yang Bin , Wu Wei , Liu Xuan , Li Haiqian 
Published: July 2021

AbstractThe purpose of this study was to analyze the association between next-generation sequencing (NGS) genotypic profiles and conventional clinicopathologic characteristics in patients with acute myeloid leukemia (AML) with NPM1 mutation (NPM1mut). We selected 238 NPM1mut patients with available NGS information on 112 genes related to blood diseases using the χ2 and Mann-Whitney U tests and a multivariable logistic model to analyze the correlation between genomic alterations and clinicopathologic parameters. Compared with the NPM1mut/FLT3-ITD(−) group, the NPM1mut/FLT3-ITD(+) group presented borderline frequent M5 morphology [78/143 (54.5%) vs. 64/95 (67.4%); P = 0.048], higher CD34- and CD7-positive rates (CD34: 20.6% vs. 47.9%, P < 0.001; CD7: 29.9% vs. 61.5%, P < 0.001) and a lack of favorable−/adverse-risk karyotypes (6.4% vs. 0%; P = 0.031). In the entire NPM1mut cohort, 240 NPM1 mutants were identified, of which 10 (10/240, 4.2%) were missense types. When confining the analysis to the 205 cases with NPM1mut insertions/deletions-type and normal karyotype, multivariable logistic analysis showed that FLT3-ITD was positively correlated with CD34 and CD7 expressions (OR = 5.29 [95% CI 2.64–10.60], P < 0.001; OR = 3.47 [95% CI 1.79–6.73], P < 0.001, respectively). Ras-pathway mutations were positively correlated with HLA-DR expression (OR = 4.05 [95% CI 1.70–9.63], P = 0.002), and KRAS mutations were negatively correlated with MPO expression (OR = 0.18 [95% CI 0.05–0.62], P = 0.007). DNMT3A-R882 was positively correlated with CD7 and HLA-DR expressions (OR = 3.59 [95% CI 1.80–7.16], P < 0.001; OR = 13.41 [95% CI 4.56–39.45], P < 0.001, respectively). DNMT3A mutation was negatively correlated with MPO expression (OR = 0.35 [95% CI 1.48–8.38], P = 0.004). TET2/IDH1 mutations were negatively correlated with CD34 and CD7 expressions (OR = 0.26 [95% CI 0.11–0.62], P = 0.002; OR = 0.30 [95% CI 0.14–0.62], P = 0.001, respectively) and positively correlated with MPO expression (OR = 3.52 [95% CI 1.48–8.38], P = 0.004). In conclusion, NPM1mut coexisting mutations in signaling pathways (FLT3-ITD and Ras-signaling pathways) and methylation modifiers (DNMT3A and TET2/IDH1) are linked with the expressions of CD34, CD7, HLA-DR and MPO, thereby providing a mechanistic explanation for the immunophenotypic heterogeneity of this AML entity.
Computational analysis for identification of early diagnostic biomarkers and prognostic biomarkers of liver cancer based on GEO and TCGA databases and studies on pathways and biological functions affecting the survival time of liver cancer
Authors: Gao Shiyong , Gang Jian , Yu Miao , Xin Guosong , Tan Huixin 
Published: July 2021

Abstract
Background
Liver cancer is the sixth most commonly diagnosed cancer and the fourth most common cause of cancer death. The purpose of this work is to find new diagnostic biomarkers or prognostic biomarkers and explore the biological functions related to the prognosis of liver cancer.

Methods
GSE25097 datasets were firstly obtained and compared with TCGA LICA datasets and an analysis of the overlapping differentially expressed genes (DEGs) was conducted. Cytoscape was used to screen out the Hub Genes among the DEGs. ROC curve analysis was used to screen the Hub Genes to determine the genes that could be used as diagnostic biomarkers. Kaplan-Meier analysis and Cox proportional hazards model screened genes associated with prognosis biomarkers, and further Gene Set Enrichment Analysis was performed on the prognosis genes to explore the mechanism affecting the survival and prognosis of liver cancer patients.

Results
790 DEGs and 2162 DEGs were obtained respectively from the GSE25097 and TCGA LIHC data sets, and 102 Common DEGs were identified by overlapping the two DEGs. Further screening identified 22 Hub Genes from 102 Common DEGs. ROC and survival curves were used to analyze these 22 Hub Genes and it was found that there were 16 genes with a value of AUC > 90%. Among these, the expression levels of ESR1,SPP1 and FOSB genes were closely related to the survival time of liver cancer patients. Three common pathways of ESR1, FOBS and SPP1 genes were identified along with seven common pathways of ESR1 and SPP1 genes and four common pathways of ESR1 and FOSB genes.

Conclusions
SPP1, AURKA, NUSAP1, TOP2A, UBE2C, AFP, GMNN, PTTG1, RRM2, SPARCL1, CXCL12, FOS, DCN, SOCS3, FOSB and PCK1 can be used as diagnostic biomarkers for liver cancer, among which FOBS and SPP1 genes can also be used as prognostic biomarkers. Activation of the cell cycle-related pathway, pancreas beta cells pathway, and the estrogen signaling pathway, while on the other hand inhibition of the hallmark heme metabolism pathway, hallmark coagulation pathway, and the fat metabolism pathway may promote prognosis in liver cancer patients.
Towards comprehensive mental health care: experiences and challenges of psychosocial care in Brazil
Authors: Sampaio Mariá Lanzotti , Bispo Júnior José Patrício 
Published: July 2021

Abstract
Background
Recommendations are in place for mental health (MH) care to be developed into a comprehensive, people-centred perspective and organised primarily through community services. In recent decades, Brazil has promoted psychiatric reform aimed at transforming the hospital-centred model into a psychosocial model of MH. However, current political and economic changes threaten this reform. This article analyses the comprehensive MH care offered by a Psychosocial Care Network (Rede de Atenção Psicossocial – RAPS) in Brazil.

Methods
The study involved semi-structured in-depth interviews with 33 stakeholders (policymakers, health professionals, and MH service users) and direct observation of MH services members of the RAPS. Data were analysed using framework analysis with the following dimensions: mental health services access, long-term mental health care, comprehensive mental health care, and crisis patient care.

Results
Results indicated progression towards comprehensive MH care provision. We identified MH care provided primarily by community services, featuring an ‘open door’ policy, development of localised actions and a search for autonomy. Deinstitutionalisation principles and the psychosocial model support a comprehensive view of MH by policy makers, MH professionals, and users. However, difficulties in providing comprehensive care remain, with the main challenges being insufficient services offered and difficulties in user access at all levels of care, fragile integration between services, lack of clear definitions of the responsibilities of each service, discontinuity of care, limitations in family support, and fragility in crisis patient care.

Conclusion
We highlight the need to increase funding and services of RAPS, qualification of staff professional, family support, and development of strategies for integrating services. Support and expansion of MH care depend on strengthening the Brazilian health system, which is in danger of being dismantled.