bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of childhood mortality associated with death of a mother in low-and-middle-income countries: a systematic review and meta-analysis
Authors: Nguyen Diep Thi Ngoc , Hughes Suzanne , Egger Sam , LaMontagne D. Scott , Simms Kate , Castle Phillip E. , Canfell Karen 
Published: October 2019

Abstract

Background
Death of a mother at an early age of the child may result in an increased risk of childhood mortality, especially in low-and-middle-income countries. This study aims to synthesize estimates of the association between a mother’s death and the risk of childhood mortality at different age ranges from birth to 18 years in these settings.

Methods
Various MEDLINE databases, EMBASE, and Global Health databases were searched for population-based cohort and case-control studies published from 1980 to 2017. Studies were included if they reported the risk of childhood mortality for children whose mother had died relative to those whose mothers were alive. Random-effects meta-analyses were used to pool effect estimates, stratified by various exposures (child’s age when mother died, time since mother’s death) and outcomes (child’s age at risk of child death).

Results
A total of 62 stratified risk estimates were extracted from 12 original studies. Childhood mortality was associated with child’s age at time of death of a mother and time since a mother’s death. For children whose mother died when they were ≤ 42 days, the relative risk (RR) of dying within the first 1–6 months of the child’s life was 35.5(95%CI:9.7–130.5, p [het] = 0.05) compared to children whose mother did not die; by 6–12 months this risk dropped to 2.8(95%CI:0.7–10.7). For children whose mother died when they were ≤ 1 year, the subsequent RR of dying in that year was 15.9(95%CI:2.2–116.1,p [het] = 0.02), compared to children whose mother lived. For children whose mother died when they were ≤ 5 years of age, the RR of dying before aged 12 was 4.1(95%CI:3.0–5.7),p [het] = 0.83. Mortality was also elevated in specific analysis among children whose mother died when child was older than 42 days. Overall, for children whose mother died < 6 and 6+ months ago, RRs of dying before reaching adulthood (≤18 years) were 4.7(95%CI:2.6–8.7,p [het] = 0.2) and 2.1(95%CI:1.3–3.4,p [het] = 0.7), respectively, compared to children whose mother lived.

Conclusions
There is evidence of an association between the death of a mother and childhood mortality in lower resource settings. These findings emphasize the critical importance of women in family outcomes and the importance of health care for women during the intrapartum and postpartum periods and throughout their child rearing years.
Carica papaya extract in dengue: a systematic review and meta-analysis
Authors: Rajapakse Senaka , de Silva Nipun Lakshitha , Weeratunga Praveen , Rodrigo Chaturaka , Sigera Chathurani , Fernando Sumadhya Deepika 
Published: October 2019

Abstract

Background
Carica papaya (CP) extract is becoming popular as an unlicensed herbal remedy purported to hasten recovery in dengue infection, mostly based on observations that it may increase platelet counts. This systematic review and meta-analysis aims to critically analyze the evidence from controlled clinical trials on the efficacy and safety of CP extract in the treatment of dengue infection.

Methods
PubMed, LILACS and Google Scholar were searched for randomized or non-randomized trials enrolling patients with suspected or confirmed dengue where CP extract was compared, as a treatment measure, against standard treatment. Recovery of platelet counts as well as other clinical indicators of favourable outcome (duration of hospital stay, prevention of plasma leakage, life threatening complications, and mortality) were assessed.

Results
Nine studies (India-6, Pakistan-1, Indonesia-1, Malaysia-1) met the inclusion criteria. Seven studies showed an increase in platelet counts in patients receiving CP extract, while one study showed no significant difference between the two groups, and direct comparison was not possible in the remaining study. Serious adverse events were not reported. CP extract may reduce the duration of hospital stay (mean difference − 1.98 days, 95% confidence interval − 1.83 to − 2.12, 3 studies, 580 participants, low quality evidence), and cause improvement in mean platelet counts between the first and fifth day of treatment (mean difference 35.45, 95% confidence interval 23.74 to 47.15, 3 studies, 129 participants, low quality evidence). No evidence was available regarding other clinical outcomes.

Conclusions
The clinical value of improvement in platelet count or early discharge is unclear in the absence of more robust indicators of favourable clinical outcome. Current evidence is insufficient to comment on the role of CP extract in dengue. There is a need for further well designed clinical trials examining the effect of CP on platelet counts, plasma leakage, other serious manifestations of dengue, and mortality, with clearly defined outcome measures.
Rare cytogenetic abnormalities and their clinical relevance in pediatric acute leukemia of Saudi Arabian population
Authors: Alkhayat Nawaf , Elyamany Ghaleb , Elborai Yasser , Sedick Qanita , Alshahrani Mohammad , Al Sharif Omar , Alenezy Abdulmalik , Hammdan Amjad , Elghezal Hatem , Alsuhaibani Omar , Aljabry Mansour S. , AlMoshary May , Al Mussaed Eman 
Published: October 2019

Abstract

Background
Childhood Acute Leukemia (AL) is characterized by recurrent genetic aberrations in 60% of AML cases and 90% of ALL cases. Insufficient data exists of rare cytogenetic abnormalities in AL. Therefore, we tested rare cytogenetic abnormalities occurring in childhood AL and its effect on clinical prognosis in patients diagnosed at our institution from 2010 to 2017.

Results
Among 150 cases of AL, we detected 9 cases with rare chromosomal abnormalities. We found two hypodiploid (2n-) cases: 2n-,t (5;14)(q31;q32) and t (3;11;19)(q21;q23;q13.1) in ALL patients. AML patients showed t (7;14)(q22;q32), t (11;17)(p15;q21), t (11;20) (p15;q11), t (12;17)(q15;q23) and t (11;20)(p15;q11). Both t (1;15)(q10;q10) and t (17;19)(q21;p13.3) occurred in a case with biphenotypic AL. Complete remission (CR) status was attained in 3 patients and 6 patients never attained CR or relapsed/demised.

Conclusion
The study highlighted that rare cytogenetic abnormalities are associated with a poor prognosis. This finding is not well reported in the literature suggesting that ongoing cytogenetic studies for rare abnormalities associated with pediatric leukaemia are warranted.
Green synthesis of spiro[indoline-3,4′-pyrano[2,3-c]pyrazoles] using Fe3O4@l-arginine as a robust and reusable catalyst
Authors: Ghasemzadeh Mohammad Ali , Mirhosseini-Eshkevari Boshra , Abdollahi-Basir Mohammad Hossein 
Published: October 2019

Abstract
The synthesized Fe3O4@l-arginine showed strong catalytic performance in the one-pot synthesis of spiropyranopyrazoles via the reactions of hydrazines, β-keto esters, isatins, and malononitrile or ethyl cyanoacetate under solvent-free conditions. The biologically active heterocyclic compounds including spiropyranopyrazole derivatives were efficiently synthesized in short reaction times and excellent yields in the presence of Fe3O4/l-arginine at room temperature. The highlighted features of the Fe3O4@l-arginine nanocomposite are highly stable, easy to separate, low loading, cost-effective with easy preparation and reusability of the catalyst. The heterogeneous nanocomposite was fully characterized by SEM, EDX, FT-IR, XRD and TEM analysis.
Dietary intakes and biomarker patterns of folate, vitamin B6, and vitamin B12 can be associated with cognitive impairment by hypermethylation of redox-related genes NUDT15 and TXNRD1
Authors: An Yu , Feng Lingli , Zhang Xiaona , Wang Ying , Wang Yushan , Tao Lingwei , Qin Zhongsheng , Xiao Rong 
Published: October 2019

AbstractBackgroundB vitamins in the one-carbon metabolism pathway (folate, vitamin B6, and vitamin B12) have been implicated in DNA methylation, and their deficiency may contribute to cognitive decline through increased homocysteine (Hcy) levels and subsequent oxidative damage. The aim of this study was to investigate whether B vitamin deficiency and increased Hcy could interact with DNA methylation of oxidative-related genes and exacerbate cognitive impairment.MethodsParticipants were selected from a large cohort study entitled the Effects and Mechanism Investigation of Cholesterol and Oxysterol on Alzheimer’s disease (EMCOA) study. We included 2533 participants who completed a selection of comprehensive cognitive tests and a semiquantitative food frequency questionnaire (FFQ) and were followed for an average of 2.3 years. The longitudinal effects of B vitamin intake on cognitive decline were examined using linear mixed-effect models. Seven mild cognitive impairment (MCI) patients, in the predementia stage of Alzheimer’s disease (AD), and fivev healthy controls were selected for the discovery of genome-wide differentially methylated CpG sites. Candidate oxidative stress-related genes significantly correlated with serum levels of B vitamins were selected for validation in 102 MCI patients and 68 controls. The correlations between DNA methylation levels and serum concentrations of B vitamins and oxidative biomarkers were analyzed with Spearman’s correlation. The interactive effects of DNA methylation and B vitamins on cognitive performance were further evaluated by multiple linear regression.ResultsIn the prospective analysis, inadequate dietary intake of vitamin B12was significantly associated with accelerated cognitive decline, whereas adequate folate, vitamin B6, and vitamin B12intakes were significantly associated with better cognitive reserve. In the case-control analysis, the DNA methylation levels of NUDT15 and TXNRD1 were examined, and significantly hypermethylated sites were identified in MCI patients. Significant correlations of hypermethylated sites with serum levels of folate, homocysteine (Hcy), and oxidative biomarkers were observed, and interactive effects of B vitamins and hypermethylated sites were significantly associated with cognitive performance.ConclusionAdequate dietary folate at baseline predicted a better cognitive reserve, while decreased serum levels of B vitamins may contribute to cognitive impairment by affecting methylation levels of specific redox-related genes.Trial registrationEMCOA, ChiCTR-OOC-17011882, Registered 5th, July 2017-Retrospectively registered,http://www.medresman.org/uc/project/projectedit.aspx?proj=2610Graphical Abstract
Long-term efficacy of interventions for actinic keratosis: protocol for a systematic review and network meta-analysis
Authors: Steeb Theresa , Heppt Markus V. , Becker Lars , Kohl Christoph , French Lars E. , Berking Carola 
Published: October 2019

Abstract

Background
Actinic keratoses (AK) are common precancerous lesions of the skin due to cumulative sun exposure. A variety of interventions are available for the treatment; however, the majority of randomised controlled trials (RCTs) and meta-analyses focus on short-term efficacy outcomes. This network meta-analysis aims to investigate the long-term (> 12 months) efficacy of interventions for AK.

Methods
To identify relevant studies, we will perform a systematic literature research in MEDLINE, Embase, and CENTRAL and hand-search pertinent trial registers. Two authors will independently screen titles and abstracts for eligibility. We will include RCTs with an inter-individual (parallel arm) design. The study population includes patients with a clinical or histopathologic diagnosis of AK. Eligibility will be restricted to the following interventions: surgical approaches, cryosurgery, ablative laser treatment, topical drug treatment with 5-fluorouracil, imiquimod, ingenol mebutate, diclofenac, or photodynamic therapy. As outcomes, we will consider the following endpoints: (1) the participant complete clearance rate, (2) the participant partial clearance rate, (3) the lesion-specific clearance, (4) the mean lesion reduction per patient, and (5) the number of withdrawals due to adverse events after at least 12 months after the end of treatment. Monotherapy or placebo will serve as a comparison. Estimates of effects from individual studies will be pooled using a random-effects model. Heterogeneity will be evaluated based on I2 and chi-square test. The risk of bias will be estimated with the Cochrane Risk of Bias Tool by two review authors independently. The quality of evidence of the outcomes will be assessed with the GRADE approach. A network meta-analysis will be performed to combine direct and indirect evidence from the included RCTs.

Discussion
The potential of interventions to achieve a sustained clearance of AK has not been assessed to date. To investigate the long-term efficacy of interventions is important as the natural disease course is highly variable and relapses occur frequently even after initial lesion clearance. This review will help to set a framework for clinical decision making in patients with AK.

Systematic review registration
CRD42018095903 (PROSPERO)
The Euler scheme for stochastic differential equations with discontinuous drift coefficient: a numerical study of the convergence rate
Authors: Göttlich S. , Lux K. , Neuenkirch A. 
Published: October 2019

Abstract
The Euler scheme is one of the standard schemes to obtain numerical approximations of solutions of stochastic differential equations (SDEs). Its convergence properties are well known in the case of globally Lipschitz continuous coefficients. However, in many situations, relevant systems do not show a smooth behavior, which results in SDE models with discontinuous drift coefficient. In this work, we analyze the long time properties of the Euler scheme applied to SDEs with a piecewise constant drift and a constant diffusion coefficient and carry out intensive numerical tests for its convergence properties. We emphasize numerical convergence rates and analyze how they depend on the properties of the drift coefficient and the initial value. We also give theoretical interpretations of some of the arising phenomena. For application purposes, we study a rank-based stock market model describing the evolution of the capital distribution within the market and provide theoretical as well as numerical results on the long time ranking behavior.
Identification of osimertinib-resistant EGFR L792 mutations by cfDNA sequencing: oncogenic activity assessment and prevalence in large cfDNA cohort
Authors: Fairclough Stephen R. , Kiedrowski Lesli A. , Lin Jessica J. , Zelichov Ori , Tarcic Gabi , Stinchcombe Thomas E. , Odegaard Justin I. , Lanman Richard B. , Shaw Alice T. , Nagy Rebecca J. 
Published: October 2019

Abstract
Cell-free DNA (cfDNA) next-generation sequencing has the potential to capture tumor heterogeneity and genomic evolution under treatment pressure in a non-invasive manner. Here, we report the detection of EGFR L792 mutations, a non-covalent mechanism of osimertinib resistance, using Guardant360 cfDNA testing in a patient with metastatic EGFR-mutant non-small cell lung cancer (NSCLC) whose disease progressed on osimertinib. We subsequently analyzed a large cohort of over 1800 additional patient samples harboring an EGFR T790M mutation and identified a concomitant L792 mutation in a total of 22 (1.2%) cases. In vitro functional assays demonstrated that the EGFR L858R/T790M/L792F/H mutations conferred intermediate-level resistance to osimertinib. Further understanding of potential acquired resistance mechanisms to targeted therapy may help inform treatment strategy in EGFR-mutant NSCLC.
Auger electrons for cancer therapy – a review
Authors: Ku Anthony , Facca Valerie J. , Cai Zhongli , Reilly Raymond M. 
Published: October 2019

AbstractBackgroundAuger electrons (AEs) are very low energy electrons that are emitted by radionuclides that decay by electron capture (e.g.111In,67Ga,99mTc,195mPt,125I and123I). This energy is deposited over nanometre-micrometre distances, resulting in high linear energy transfer (LET) that is potent for causing lethal damage in cancer cells. Thus, AE-emitting radiotherapeutic agents have great potential for treatment of cancer. In this review, we describe the radiobiological properties of AEs, their radiation dosimetry, radiolabelling methods, and preclinical and clinical studies that have been performed to investigate AEs for cancer treatment.ResultsAEs are most lethal to cancer cells when emitted near the cell nucleus and especially when incorporated into DNA (e.g.125I-IUdR). AEs cause DNA damage both directly and indirectly via water radiolysis. AEs can also kill targeted cancer cells by damaging the cell membrane, and kill non-targeted cells through a cross-dose or bystander effect. The radiation dosimetry of AEs considers both organ doses and cellular doses. The Medical Internal Radiation Dose (MIRD) schema may be applied. Radiolabelling methods for complexing AE-emitters to biomolecules (antibodies and peptides) and nanoparticles include radioiodination (125I and123I) or radiometal chelation (111In,67Ga,99mTc). Cancer cells exposedin vitroto AE-emitting radiotherapeutic agents exhibit decreased clonogenic survival correlated at least in part with unrepaired DNA double-strand breaks (DSBs) detected by immunofluorescence for γH2AX, and chromosomal aberrations. Preclinical studies of AE-emitting radiotherapeutic agents have shown strong tumour growth inhibitionin vivoin tumour xenograft mouse models. Minimal normal tissue toxicity was found due to the restricted toxicity of AEs mostly on tumour cells targeted by the radiotherapeutic agents. Clinical studies of AEs for cancer treatment have been limited but some encouraging results were obtained in early studies using111In-DTPA-octreotide and125I-IUdR, in which tumour remissions were achieved in several patients at administered amounts that caused low normal tissue toxicity, as well as promising improvements in the survival of glioblastoma patients with125I-mAb 425, with minimal normal tissue toxicity.ConclusionsProof-of-principle for AE radiotherapy of cancer has been shown preclinically, and clinically in a limited number of studies. The recent introduction of many biologically-targeted therapies for cancer creates new opportunities to design novel AE-emitting agents for cancer treatment. Pierre Auger did not conceive of the application of AEs for targeted cancer treatment, but this is a tremendously exciting future that we and many other scientists in this field envision.
The impact of certain underlying comorbidities on the risk of developing hospitalised pneumonia in England
Authors: Campling J. , Jones D. , Chalmers J. D. , Jiang Q. , Vyse A. , Madhava H. , Ellsbury G. , Slack M. 
Published: October 2019

Abstract

Background
UK specific data on the risk of developing hospitalised CAP for patients with underlying comorbidities is lacking. This study compared the likelihood of hospitalised all-cause community acquired pneumonia (CAP) in patients with certain high-risk comorbidities and a comparator group with no known risk factors for pneumococcal disease.

Methods
This retrospective cohort study interrogated data in the Hospital Episodes Statistics (HES) dataset between financial years 2012/13 and 2016/17. In total 3,078,623 patients in England (aged ≥18 years) were linked to their hospitalisation records. This included 2,950,910 individuals with defined risk groups and a comparator group of 127,713 people who had undergone tooth extraction with none of the risk group diagnoses. Risk groups studied were chronic respiratory disease (CRD), chronic heart disease (CHD), chronic liver disease (CLD), chronic kidney disease (CKD), diabetes (DM) and post bone marrow transplant (BMT). The patients were tracked forward from year 0 (2012/13) to Year 3 (2016/17) and all diagnoses of hospitalised CAP were recorded. A Logistic regression model compared odds of developing hospitalised CAP for patients in risk groups compared to healthy controls. The model was simultaneously adjusted for age, sex, strategic heath authority (SHA), index of multiple deprivation (IMD), ethnicity, and comorbidity. To account for differing comorbidity profiles between populations the Charlson Comorbidity Index (CCI) was applied. The model estimated odds ratios (OR) with 95% confidence intervals of developing hospitalised CAP for each specified clinical risk group.

Results
Patients within all the risk groups studied were more likely to develop hospitalised CAP than patients in the comparator group. The odds ratios varied between underlying conditions ranging from 1.18 (95% CI 1.13, 1.23) for those with DM to 5.48 (95% CI 5.28, 5.70) for those with CRD.

Conclusions
Individuals with any of 6 pre-defined underlying comorbidities are at significantly increased risk of developing hospitalised CAP compared to those with no underlying comorbid condition. Since the likelihood varies by risk group it should be possible to target patients with each of these underlying comorbidities with the most appropriate preventative measures, including immunisations.
Added value of three-dimensional digital subtraction angiography, using dual-volume reconstruction technique, in post-treatment follow-up of cerebral aneurysms
Authors: Abdel Samad Amr Mahmoud , Ibrahim Yosra Abdelzaher , Othman Amal Ibrahim A. 
Published: October 2019

Abstract

Background
To assess the added value of the dual-volume technique when used with the routine single-volume 3D DSA in the follow-up of endovascularly treated aneurysms.

Results
Seventeen patients (10 females and 7 males) who underwent coiling of their cerebral aneurysms were assessed by 3D DSA using single- and dual-volume techniques. Recanalization of the aneurysm was depicted in 10 cases on the dual-volume technique, only 4 of which were detected on the single-volume 3D DSA technique. Thus, the use of the dual-volume technique upgraded our management plan from follow-up to re-treatment in 6 cases (35%)

Conclusion
The dual-volume technique of 3D DSA is superior to the single-volume technique in visualization of the endovascular devices distinctly, resulting in better evaluation of the aneurysm recanalization and its relation to the parent vessel and occluding device.