bluuebunny/crossref_metadata_2025_split huggingface dataset:
Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial
Authors: Wei Andrew H. , Montesinos Pau , Ivanov Vladimir , DiNardo Courtney D. , Novak Jan , Laribi Kamel , Kim Inho , Stevens Don A. , Fiedler Walter , Pagoni Maria , Samoilova Olga , Hu Yu , Anagnostopoulos Achilles , Bergeron Julie , Hou Jing-Zhou , Murthy Vidhya , Yamauchi Takahiro , McDonald Andrew , Chyla Brenda , Gopalakrishnan Sathej , Jiang Qi , Mendes Wellington , Hayslip John , Panayiotidis Panayiotis 
Published: March 2020

Abstract
Effective treatment options are limited for patients with acute myeloid leukemia (AML) who cannot tolerate intensive chemotherapy. Adults age ≥18 years with newly diagnosed AML ineligible for intensive chemotherapy were enrolled in this international phase 3 randomized double-blind placebo-controlled trial. Patients (N = 211) were randomized 2:1 to venetoclax (n = 143) or placebo (n = 68) in 28-day cycles, plus low-dose cytarabine (LDAC) on days 1 to 10. Primary end point was overall survival (OS); secondary end points included response rate, transfusion independence, and event-free survival. Median age was 76 years (range, 36-93 years), 38% had secondary AML, and 20% had received prior hypomethylating agent treatment. Planned primary analysis showed a 25% reduction in risk of death with venetoclax plus LDAC vs LDAC alone (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.52-1.07; P = .11), although not statistically significant; median OS was 7.2 vs 4.1 months, respectively. Unplanned analysis with additional 6-month follow-up demonstrated median OS of 8.4 months for the venetoclax arm (HR, 0.70; 95% CI, 0.50-0.98; P = .04). Complete remission (CR) plus CR with incomplete blood count recovery rates were 48% and 13% for venetoclax plus LDAC and LDAC alone, respectively. Key grade ≥3 adverse events (venetoclax vs LDAC alone) were febrile neutropenia (32% vs 29%), neutropenia (47% vs 16%), and thrombocytopenia (45% vs 37%). Venetoclax plus LDAC demonstrates clinically meaningful improvement in remission rate and OS vs LDAC alone, with a manageable safety profile. Results confirm venetoclax plus LDAC as an important frontline treatment for AML patients unfit for intensive chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT03069352.
Exploiting sequence labeling framework to extract document-level relations from biomedical texts
Authors: Li Zhiheng , Yang Zhihao , Xiang Yang , Luo Ling , Sun Yuanyuan , Lin Hongfei 
Published: March 2020

AbstractBackgroundBoth intra- and inter-sentential semantic relations in biomedical texts provide valuable information for biomedical research. However, most existing methods either focus on extracting intra-sentential relations and ignore inter-sentential ones or fail to extract inter-sentential relations accurately and regard the instances containing entity relations as being independent, which neglects the interactions between relations. We propose a novel sequence labeling-based biomedical relation extraction method named Bio-Seq. In the method, sequence labeling framework is extended by multiple specified feature extractors so as to facilitate the feature extractions at different levels, especially at the inter-sentential level. Besides, the sequence labeling framework enables Bio-Seq to take advantage of the interactions between relations, and thus, further improves the precision of document-level relation extraction.ResultsOur proposed method obtained an F1-score of 63.5% on BioCreative V chemical disease relation corpus, and an F1-score of 54.4% on inter-sentential relations, which was 10.5% better than the document-level classification baseline. Also, our method achieved an F1-score of 85.1% on n2c2-ADE sub-dataset.ConclusionSequence labeling method can be successfully used to extract document-level relations, especially for boosting the performance on inter-sentential relation extraction. Our work can facilitate the research on document-level biomedical text mining.
Transcriptomic and metabolomic analysis provides insights into anthocyanin and procyanidin accumulation in pear
Authors: Zhang Zhen , Tian Changping , Zhang Ya , Li Chenzhiyu , Li Xi , Yu Qiang , Wang Shuo , Wang Xinyu , Chen Xuesen , Feng Shouqian 
Published: March 2020

Abstract
Background
Pear is one of the most important fruit crops worldwide. Anthocyanins and procyanidins (PAs) are important secondary metabolites that affect the appearance and nutritive quality of pear. However, few studies have focused on the molecular mechanism underlying anthocyanin and PA accumulation in pear.

Results
We conducted metabolome and transcriptome analyses to identify candidate genes involved in anthocyanin and PA accumulation in young fruits of the pear cultivar ‘Clapp Favorite’ (CF) and its red mutation cultivar ‘Red Clapp Favorite’ (RCF). Gene–metabolite correlation analyses revealed a ‘core set’ of 20 genes that were strongly correlated with 10 anthocyanin and seven PA metabolites. Of these, PcGSTF12 was confirmed to be involved in anthocyanin and PA accumulation by complementation of the tt19–7 Arabidopsis mutant. Interestingly, PcGSTF12 was found to be responsible for the accumulation of procyanidin A3, but not petunidin 3, 5-diglucoside, opposite to the function of AtGSTs in Arabidopsis. Transformation with PcGSTF12 greatly promoted or repressed genes involved in anthocyanin and PA biosynthesis, regulation, and transport. Electrophoretic mobility shift and luciferase reporter assays confirmed positive regulation of PcGSTF12 by PcMYB114.

Conclusion
These findings identify a core set of genes for anthocyanin and PA accumulation in pear. Of these, PcGSTF12, was confirmed to be involved in anthocyanin and PA accumulation. Our results also identified an important anthocyanin and PA regulation node comprising two core genes, PcGSTF12 and PcMYB114. These results provide novel insights into anthocyanin and PA accumulation in pear and represent a valuable data set to guide future functional studies and pear breeding.
The role of drug resistance in poor viral suppression in rural South Africa: findings from a population-based study
Authors: Lippman Sheri A. , Mooney Alyssa C. , Puren Adrian , Hunt Gillian , Grignon Jessica S. , Prach Lisa M. , Gilmore Hailey J. , Truong Hong-Ha M. , Barnhart Scott , Liegler Teri 
Published: March 2020

Abstract
Background
Understanding factors driving virological failure, including the contribution of HIV drug resistance mutations (DRM), is critical to ensuring HIV treatment remains effective. We examine the contribution of drug resistance mutations for low viral suppression in HIV-positive participants in a population-based sero-prevalence survey in rural South Africa.

Methods
We conducted HIV drug resistance genotyping and ART analyte testing on dried blood spots (DBS) from HIV-positive adults participating in a 2014 survey in North West Province. Among those with virologic failure (> 5000 copies/mL), we describe frequency of DRM to protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI), report association of resistance with antiretroviral therapy (ART) status, and assess resistance to first and second line therapy. Analyses are weighted to account for sampling design.

Results
Overall 170 DBS samples were assayed for viral load and ART analytes; 78.4% of men and 50.0% of women had evidence of virologic failure and were assessed for drug resistance, with successful sequencing of 76/107 samples. We found ≥1 DRM in 22% of participants; 47% were from samples with detectable analyte (efavirenz, nevirapine or lopinavir). Of those with DRM and detectable analyte, 60% showed high–level resistance and reduced predicted virologic response to ≥1 NRTI/NNRTI typically used in first and second-line regimens.

Conclusions
DRM and predicted reduced susceptibility to first and second-line regimens were common among adults with ART exposure in a rural South African population-based sample. Results underscore the importance of ongoing virologic monitoring, regimen optimization and adherence counseling to optimize durable virologic suppression.
The spatiotemporal distribution of human brucellosis in mainland China from 2007-2016
Authors: Liang Peifeng , Zhao Yuan , Zhao Jianhua , Pan Dongfeng , Guo Zhongqin 
Published: March 2020

AbstractBackgroundDespite the considerable efforts made to address the issue of brucellosis worldwide, its prevalence in dairy products continues to be difficult to estimate and represents a key public health issue around the world today. The aim of the present study was to better understand the epidemiology of this disease in mainland China. We set out to investigate the yearly spatial distribution and possible hotspots of the disease.MethodsHuman brucellosis data from mainland China between 2007 and 2016 were collected from the China Information System for Disease Control and Prevention. A geographic information system ArcGIS10.3 (ESRI, Redlands) was used to identify potential changes in the spatial and temporal distribution of human brucellosis in mainland China during the study period. These distributions were evaluated using three-dimensional trend analysis and spatial autocorrelation analyse. A gravity-center was used to analyse the migration track of human brucellosis.ResultsA total of 399,578 cases of human brucellosis were reported during the 10-year study period. The monthly incidence of brucellosis in China demonstrates clear seasonality. Spring and summer are the peak seasons, while May is the peak month for brucellosis. Three-dimensional trend analysis suggests that brucellosis is on the rise from south to north, and that the epidemic situation in northern China is more severe. Between 2007 and 2016, the overall migration distance of the brucellosis incidence gravity-center was 906.43 km, and the direction was southwest. However, the overall gravity center of brucellosis was still in the northern part of China. In the global autocorrelation analysis, brucellosis in China demonstrated a non-random distribution between 2013 and 2014, with spatial autocorrelation (Z > 1.96,P < 0.05) and a clustering trend, while no clustering trend was found from 2007 to 2012 or from 2015 to 2016. In the local autocorrelation analysis, a Low-Low cluster phenomenon was found in the south of China in 2013 and 2014.ConclusionHuman brucellosis remains a widespread challenge, particularly in northern China. The hotspots highlight potential high-risk areas which may require special plans and resources for monitoring and controlling the disease.
A novel splice site indel alteration in the EIF2AK3 gene is responsible for the first cases of Wolcott-Rallison syndrome in Hungary
Authors: Sümegi Andrea , Hendrik Zoltán , Gáll Tamás , Felszeghy Enikő , Szakszon Katalin , Antal-Szalmás Péter , Beke Lívia , Papp Ágnes , Méhes Gábor , Balla József , Balla György 
Published: March 2020

Abstract
Background
Wolcott-Rallison Syndrome (WRS) is a rare autosomal recessive disease that is the most common cause of neonatal diabetes in consanguineous families. WRS is caused by various genetic alterations of the Eukaryotic Translation Initiation Factor 2-Alpha Kinase 3 (EIF2AK3) gene.

Methods
Genetic analysis of a consanguineous family where two children were diagnosed with WRS was performed by Sanger sequencing. The altered protein was investigated by in vitro cloning, expression and immunohistochemistry.

Results
The first cases in Hungary, − two patients in one family, where the parents were fourth-degree cousins - showed the typical clinical features of WRS: early onset diabetes mellitus with hyperglycemia, growth retardation, infection-induced multiple organ failure. The genetic background of the disease was a novel alteration in the EIF2AK3 gene involving the splice site of exon 11– intron 11–12 boundary: g.53051_53062delinsTG. According to cDNA sequencing this created a new splice site and resulted in a frameshift and the development of an early termination codon at amino acid position 633 (p.Pro627AspfsTer7). Based on in vitro cloning and expression studies, the truncated protein was functionally inactive. Immunohistochemistry revealed that the intact protein was absent in the islets of pancreas, furthermore insulin expressing cells were also dramatically diminished. Elevated GRP78 and reduced CHOP protein expression were observed in the liver.

Conclusions
The novel genetic alteration causing the absence of the EIF2AK3 protein resulted in insufficient handling of severe endoplasmic reticulum stress, leading to liver failure and demise of the patients.
Risk factor analysis for inaccurate pre-operative MRI staging in rectal cancer
Authors: Cai Zerong , Xie Xiaoyu , Chen Yufeng , Chen Zexian , Cao Wuteng , Saad Khamis Salem Saeed , Zou Yifeng , Lan Ping , Wu Xiaojian 
Published: March 2020

Abstract
Background
Various tumor characteristics might lead to inaccurate local MRI-defined stage of rectal cancer and the purpose of this study was to explore the clinicopathological factors that impact on the precision pre-treatment MRI-defined stage of rectal cancer.

Methods
A retrospectively analysis was conducted in non-metastatic rectal cancer patients who received radical tumor resection without neoadjuvant treatment during 2007–2015 in the Sixth Affiliated Hospital of Sun Yat-sen University. Clinical T stage and N stage defined by pelvic enhanced MRI and pathological stage were compared and patients were subdivided into accurate-staging, over-staging and under-staging subgroups. Logistic regressions were used to explore risk factors for over-staging or under-staging.

Results
Five hundred fifty-one cases of patients were collected. Among them, 109 cases (19.4%) of patients were over-T-staged and 50 cases (8.9%) were under-T-staged, while 78 cases (13.9%) were over-N-staged and 75 cases (13.3%) were under-N-staged. Logistic regression suggested that pre-operative bowel obstruction was risk factor for over-T-staging (OR = 3.120, 95%CI: 1.662–5.857, P < 0.001) as well as over-N-staging (OR = 3.494, 95%CI: 1.797–6.794, P < 0.001), while mucinous adenocarcinoma was a risk factor for under-N-staging (OR = 4.049, 95%CI: 1.876–8.772, P < 0.001). Patients with larger tumor size were at lower risk for over-T-staging (OR = 0.837, 95%CI: 0.717–0.976, P = 0.024) and higher risk for over-N-staging (OR = 1.434, 95%CI: 1.223–1.680, P < 0.001).

Conclusion
Bowel obstruction, mucinous adenocarcinoma and tumor size might have impact on the pre-operative MRI T staging or N staging of rectal cancer. Our results reminded clinicians to assess clinical stage individually in such rectal cancer patients.
The disappearance of white matter in an adult-onset disease: a case report
Authors: Ho Cyrus SH , Mangelsdorf Simone , Walterfang Mark 
Published: March 2020

Abstract
Background
Vanishing white matter disease (VWMD) is one of the most prevalent hereditary white matter diseases in childhood, but it is increasingly recognised in adulthood with high phenotypic variation and severity.

Case presentation
We report a case of an adult female presenting with emotional lability and cognitive impairment, in addition to progressive dystonia, ataxia, postural instability and recurrent falls. Magnetic resonance imaging (MRI) of the brain and genetic testing confirmed the diagnosis of VWMD.

Conclusions
VWMD has a broad clinical presentation in adulthood, and the age at onset of symptoms is one of its most important prognostic factors. It is crucial to recognize the pathognomonic MRI patterns and consider VWMD as a differential diagnosis when assessing patients presenting with psychiatric, cognitive and non-specific neurological symptoms.
Social and economic variables related with Paraquat self-poisoning: an ecological study
Authors: Buendía Jefferson Antonio , Restrepo Chavarriaga Gabriel Jaime , Zuluaga Andres F. 
Published: March 2020

Abstract
Background
Paraquat self-poisonings constitute a significant contributor to the global burden of suicide. Our aim was to evaluate the relationship between social and economic variables with the incidence of self-poisoning with Paraquat in the northeast of Colombia.

Methods
Records of 154 cases of self-poisoning with Paraquat and several socio-economic variables of six regions of northeast of Colombia were analyzed.

Results
Most of the cases were mestizos, farmworkers, between 20 and 29 years, with intentional exposure using the oral route. Multivariate analyses revealed significant associations among the incidence of self-poisoning with PQ with the ecological factors such as poverty greater than 30% (IRR 15.9 IC95% 5.56–44.72), land Gini index < 0.7 (IRR 7.11 IC95% 3.58–14.12), private health insurance < 40% (IRR 3.39 IC95% 1.30–8.82) and planted area > 10% (IRR 2.47 IC95% 1.60–3.80).

Conclusion
There is a relationship between ecological factors and, as such, this study opens the way to further developments in the field.
Recognizing and responding to women experiencing homelessness with gendered and trauma-informed care
Authors: Milaney Katrina , Williams Nicole , Lockerbie Stacy Lee , Dutton Daniel J. , Hyshka Elaine 
Published: March 2020

Abstract
Background
The purpose of this study is to highlight the experiences of women who are often hidden in what we know and understand about homelessness, and to make policy and practice recommendations for women-centred services including adaptations to current housing interventions.

Methods
Three hundred survey interviews were conducted with people experiencing homelessness in Calgary, Alberta, Canada. The survey instrument measured socio-demographics, adverse childhood experiences, mental and physical health, and perceived accessibility to resources. Eighty-one women participants were identified as a subsample to be examined in greater depth. Descriptive statistics and logistic regressions were calculated to provide insight into women respondents’ characteristics and experiences of homelessness and how they differed from men’s experiences.

Results
Women’s experiences of homelessness are different from their male counterparts. Women have greater mental health concerns, higher rates of diagnosed mental health issues, suicidal thoughts and attempts, and adverse childhood trauma. The results should not be considered in isolation, as the literature suggests, because they are highly interconnected.

Conclusion
In order to ensure that women who are less visible in their experiences of homelessness are able to access appropriate services, it is important that service provision is both gender specific and trauma-informed. Current Housing First interventions should be adapted to ensure women’s safety is protected and their unique needs are addressed.
Increasing pelvic incidence is associated with more global sagittal imbalance in ankylosing spondylitis with thoracolumbar kyphosis: an observational retrospective study of 94 cases
Authors: Song Diyu , Zheng Guoquan , Wang Tianhao , Qi Dengbin , Wang Yan 
Published: March 2020

Abstract
Background
Ankylosing spondylitis (AS) patients with kyphosis have an abnormal spinopelvic alignment and pelvic morphology. Most studies focus on the relationship of pelvic tilt (PT) or sacral slope (SS) and deformity, and relatively few studies have addressed the relationship between pelvic incidence (PI) and kyphosis in AS patients. The purpose of this study is to analyze the correlation between pelvic incidence (PI) and the spinopelvic parameters describing local deformity or global sagittal balance in AS patients with thoracolumbar kyphosis.

Methods
A total of 94 patients with AS (91 males and 3 females) and 30 controls (27 males and 3 females) were reviewed. The mean age was 36.8 years in AS patients and 34.4 years in controls. Gender ratios and mean age were similar in both group. Sagittal spinopelvic parameters, including PI, PT, SS, thoracic kyphosis (TK), thoracolumbar kyphosis (TLK), lumbar lordosis (LL), sagittal vertical axis (SVA), the first thoracic vertebra pelvic angle (TPA), spinosacral angle (SSA) and spinopelvic angle (SPA) were measured. The same spine surgeons measured all the parameters of the AS and control group. All the sagittal spinopelvic parameters were compared between the groups. The relationship between PI and other spinopelvic parameters was analyzed with Pearson correlation (r) and unary linear regression model.

Results
All the sagittal parameters were found to be significantly different between AS patients and controls. Compared with the control group, the AS patients had significantly higher PI(47.4° vs. 43.2°, P < 0.001). Correlation analysis revealed that PI in AS patients was significantly positively correlated with TPA(r = 0.533, R2 = 0.284, P < 0.001), and negatively correlated with SPA(r = − 0.504, R2 = 0.254, P < 0.001). However, no correlations were found between PI and SVA, SSA, TK, TLK or LL in AS patients.

Conclusion
This study revealed that increasing PI was significantly correlated with more global sagittal imbalance, not with the local deformity in AS patients with thoracolumbar kyphosis.
Implementation of palliative care consult Service in Hungary – integration barriers and facilitators
Authors: Zemplényi Antal T. , Csikós Ágnes , Csanádi Marcell , Mölken Maureen Rutten-van , Hernandez Carmen , Pitter János G. , Czypionka Thomas , Kraus Markus , Kaló Zoltán 
Published: March 2020

Abstract
Background
The Palliative Care Consult Service (PCCS) programme was among the first initiations in Hungary to provide palliative care for patients admitted to hospital. The PCCS team provides palliative care for mainly cancer patients and their family members and manages the patient pathway after being discharged from the hospital. The service started in 2014 with 300–400 patient visits per year. The aim of this study is to give a comprehensive overview of the PCCS programme guided by a conceptual framework designed by SELFIE (“Sustainable intEgrated chronic care modeLs for multi-morbidity: delivery, FInancing, and performancE”), a Horizon2020 funded EU project and to identify the facilitators and barriers to its wider implementation.

Methods
PCCS has been selected by the SELFIE consortium for in-depth evaluation as one of the Hungarian integrated care models for persons with multi-morbidity. The qualitative analysis of the PCCS programme was based on available documents of the care provider and interviews with different stakeholders related to the programme.

Results
The integrated, multidisciplinary and patient-centred approach was well-received among the patients, family members and clinical departments, as verified by the increasing number of requests for consultations. As a result of the patient pathway management across providers (e.g. from inpatient care to homecare) a higher level of coordination could be achieved in the continuity of care for seriously-ill patients. The regulatory framework has only partially been established, policies to integrate care across organizations and sectors and adequate financial mechanism to support the enhancement and sustainability of the PCCS are still missing.

Conclusions
The service integration of palliative care could be implemented successfully in an academic hospital in Hungary. However, the continuation and enhancement of the programme will require further evidence on the performance of the integrated model of palliative care and a more systematic approach particularly regarding the evaluation, financing and implementation process.