bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of addition of cyclin-dependent kinase 4 & 6 (CDK 4/6) inhibitor to endocrine therapy in the cardiovascular toxicity in advanced breast cancer patients: A systematic review and meta-analysis.
Authors: Bebero Katrina Gaelic Moncano , Marayag Eric John Arca , Regala Eugenio Vistan 
Published: October 2019

134 Background: The addition of CDK 4/6 inhibitor to endocrine therapy has shown promising advantage over endocrine therapy alone. Cardiac toxicity impacts quality of life and poses potential confounder to mortality. This study aims to review an analyze the cardiovascular toxicities reported among clinical trials of addition of CDK 4/6 inhibitors to endocrine therapy. Methods: Literature search was conducted through PubMed, Cochrane, ASCO, and ESMO databases. Included were articles with Phase II/III randomized clinical trials in metastatic breast cancer with assessable cardiovascular toxicity report. PRISMA Assessment Tool was used to validate the articles. Review Manager Version 5.3 was used for analyses. Risk ratio with corresponding 95% confidence interval were the main outcome measures. Results: Initial screening generated 543 articles, 38 of which were deemed relevant from which 4 articles were eligible for meta-analysis. A total of 2079 patients were analyzed. Risk ratio for all cardiovascular toxicity was 1.39 (95% CI:0.91,2.10, p=0.010). Identified all-grade cardiovascular toxicities with corresponding risk ratios were hypertension 1.14(95% CI: 0.86, 1.50, p=0.22), QT prolongation 2.30(95%CI:1.31,4.01, p=0.79), deep vein thrombosis 2.5 (95% CI: 0.12,51.59, p=0.55), pulmonary embolism 3.5(95% CI: 0.18, 67.38, p=0.41), atrial fibrillation 2.5 (95% CI: 0.12, 51.79, p=0.55). Hypertension and QT prolongation were observed in both palbociclib and ribociclib studies while deep vein thrombosis, pulmonary embolism, and atrial fibrillation were only seen in ribociclib. Conclusions: Addition of CDK 4/6 inhibitor to endocrine therapy increases the risk for cardiovascular toxicity by 39% compared to endocrine therapy alone. Hypertension and QT prolongation were the common cardiovascular adverse events with increase in risk by 14% and 130%, respectively.
MAIA (Medical Artificial Intelligence Assistant) as interface for a new cancer healthcare integrative platform.
Authors: Pino Luis Eduardo , Large Eduardo , Mejía Jorge , Triana Ivan Camilo 
Published: October 2019

25 Background: Cancer healthcare systems are an example of inequity and waste in low and middle income countries. Access to high quality cancer pathways focused in early diagnosis, molecular biology, proper staging and evidence based treatments are scarce and the patient`s care experience is dramatic and difficult in a majority of cases. There are no integrative healthcare models based on new technologies that improve outcomes and make more comfortable and expeditious all the patient and physician´s journey in cancer. Methods: Our team developed and trained a talkbot called MAIA (Medical Artificial Intelligence Assistant) using an algorithmic translation of medical language focused in the state or art for non small cell lung cancer. Our clinical team developed decision trees in diagnosis, staging, medical and surgical treatment and molecular biology that were incorporated in a virtual platform and then integrated onto a narrow artificial intelligence bot brain using neural networks with the proposal of generate clinical support to the physician and create a standard text using the verbal information captured in the oncological consultation and integrated images (reports) through a image edition software and then create a unique medical record without using computers by the physician. MAIA also can create medical treatment choices in first line of treatment and create alerts and alarms through an own app (MAIA Hip). Results: Our proof of concept was released in video at this link https://drive.google.com/file/d/12YtiOkhfEmIsL2bFp9T3QyfHHWxBvvKU/view?ts=5ceec096 Due to our decision trees size we can´t upload them, but are available for presentation. Conclusions: A talkbot trained as a narrow artificial intelligence interface for an integrative cancer healthcare platform (HIP) is possible through the clinical and engineer integration of languages using a neural network method and other software tools. MAIA is for now a patient and physician experience improvement, but the real impact will be in the data standarization and acquisition for advanced analytics. The final scope of MAIA HIP will be a blockchain for cancer in low and middle income countries.
Effect of Dosage of 17ß-Estradiol on Uterine Growth in Turner Syndrome—A Randomized Controlled Clinical Pilot Trial
Authors: Cleemann Line , Holm Kirsten , Fallentin Eva , Møller Nini , Kristensen Bent , Skouby Sven O , Leth-Esbensen Per , Jeppesen Eva M , Jensen Andreas K , Gravholt Claus H 
Published: October 2019

AbstractContextMost Turner syndrome (TS) girls need exogenous estrogen treatment to induce puberty and normal uterine growth. After puberty, the optimal estrogen treatment protocol has not been determined.ObjectiveTo compare 2 doses of oral 17ß-estradiol on uterine size.DesignA double-blind, 5-year randomized controlled clinical trial.SettingAmbulatory care.ParticipantsTwenty young TS women (19.2 ± 2.5 years, range 16.0–24.9) participated. Sixteen patients completed the study. No patients withdrew due to adverse effects.InterventionThe lower dose (LD) group took 2 mg 17ß-estradiol/d orally and placebo. The higher dose (HD) group took 4 mg 17ß-estradiol/d orally.Main Outcome Measure(s)Uterine volume evaluated by transabdominal ultrasound yearly.ResultsUterine size increased significantly more in the HD group compared with the LD group (P = 0.038), with a gain in uterine volume within the first 3 years of treatment of 19.6 mL (95% confidence interval [CI] = 4.0-19.0) in the HD group compared with 11.5 mL (95% CI = 11.2-27.9) in the LD group. The difference in 3-year gain was 8.1 mL (95% CI = 0.7-15.9). At the last visit, there were no significant differences in uterine volume between the groups.ConclusionHD oral 17ß-estradiol induces a steeper increase in uterine volume within the first years of treatment compared with the LD. However, the uterine growth potential seems to be the same in most young TS women making the duration of treatment equally significant as estrogen dose, although a few TS women did not experience sufficient uterine growth on 2 mg of estradiol.ClinicalTrials.govNCT00134745Abbreviations: BMI, body mass index; BSA, body surface area; DHEAS, dihydroepiandrosteronesulfate; HD, higher dose; HRT, hormone replacement therapy; LD, lower dose; TS, Turner syndrome; US, ultrasound
Maternal Exposure to Environmental Disruptors and Sexually Dimorphic Changes in Maternal and Neonatal Oxidative Stress
Authors: Puttabyatappa Muraly , Banker Margaret , Zeng Lixia , Goodrich Jaclyn M , Domino Steven E , Dolinoy Dana C , Meeker John D , Pennathur Subramaniam , Song Peter X K , Padmanabhan Vasantha 
Published: October 2019

Abstract

Context
Early pregnancy exposure to endocrine disrupting chemicals (EDCs) may contribute to poor birth outcomes through oxidative stress (OS)-mediated disruption of the maternal and fetal milieu. Most studies have investigated the effect of single EDC exposures on OS.

Objective
Assess the association of uniquely weighted mixtures of early pregnancy exposures with the maternal and neonatal OS markers.

Design
Prospective analysis of mother–infant dyads

Setting
University hospital.

Participants
56 mother–infant dyads.

Main Outcome Measures
The association of OS markers (nitrotyrosine, dityrosine, chlorotyrosine) in maternal first trimester and term, and cord blood plasma with maternal first trimester exposure levels of each of 41 toxicants (trace elements, metals, phenols, and phthalates) from 56 subjects was analyzed using Spearman correlations and linear regression. The association of OS markers with inflammatory cytokines and birth outcomes were analyzed by Spearman correlation and linear regression analysis, respectively. Weighted mixtures of early pregnancy exposures were created by principal component analysis and offspring sex-dependent and independent associations with oxidative stress markers were assessed.

Results
(1) An inverse relationship between levels of maternal/cord OS markers and individual EDCs was evident. In contrast, when assessed as EDC mixtures, both direct and inverse associations were evident in a sex-specific manner; (2) the maternal term OS marker, nitrotyrosine, was inversely associated with gestational age, and (3) both direct and inverse associations were evident between the 3 OS markers and individual cytokines.

Conclusions
Provides proof of concept that effects of exposures on OS varies when assessed as EDC mixtures versus individually.
Noninvasive Evaluation of GPR119 Agonist Effects on β-Cell Mass in Diabetic Male Mice Using 111In-Exendin-4 SPECT/CT
Authors: Murakami Takaaki , Fujimoto Hiroyuki , Fujita Naotaka , Hamamatsu Keita , Matsumoto Koji , Inagaki Nobuya 
Published: October 2019

Abstract
Longitudinal observation of pancreatic β-cell mass (BCM) remains challenging because noninvasive techniques for determining BCM in vivo have not been established. Such observations would be useful for the monitoring of type 2 diabetes mellitus, a progressive disease involving loss of pancreatic BCM and function. An indium 111 (111In)–labeled exendin-4 derivative ([Lys12(111In-BnDTPA-Ahx)]exendin-4) targeting the glucagon-like peptide-1 receptor has been developed recently as a promising probe for quantifying the BCM noninvasively. In the present study, we used the 111In-exendin-4 single-photon emission CT/CT (SPECT/CT) technique to investigate the efficacy of DS-8500a, a novel G protein–coupled receptor-119 agonist currently under investigation for type 2 diabetes mellitus treatment in prediabetic db/db mice under dietary restriction. During the 8-week study, the treatment of mice with DS-8500a delayed and attenuated the progression of glucose intolerance compared with mice under dietary restriction alone. 111In-exendin-4 SPECT/CT of db/db mice revealed continuously decreasing radioactive isotope (RI) intensity in the pancreas during the 8-week intervention. DS-8500a attenuated this decrease and preserved pancreatic RI accumulation compared with dietary restriction alone at the end of the observation period. This result was corroborated not only by ex vivo pancreatic analysis using the [Lys12(111In-BnDTPA-Ahx)]exendin-4 probe but also by conventional histological BCM analysis. These results indicate that DS-8500a attenuates the progression of BCM loss beyond that of dietary restriction alone in prediabetic db/db mice. These results have shown that 111In-exendin-4 SPECT/CT will be useful for noninvasive longitudinal investigation of BCM in vivo.
Get Smart: Learning and partnership with Ethiopia’s Health Extension Programme to re-envision contraceptive service delivery to young couples
Authors: Appleford Gabrielle , Cole Claire , Ayenekulu Metsehate , Newport Sue , Mulhern Emma 
Published: October 2019

Background: Adolescents 360 (A360) implements the Smart Start (SS) programme through Ethiopia’s Health Extension Programme (HEP). SS is premised on financial planning as an entry point to discuss family planning (FP) with newly married couples and central to its delivery are the health extension workers (HEW). This article evaluates the A360 experience and learning from the process evaluation implemented by Itad to understand contextual barriers and enablers from the perspective of the HEW. Methods: A purposive sampling strategy was employed whereby 27 key stakeholders were identified from Oromia, Addis Ababa and Amhara, based on exposure to the SS programme. Findings from the action research were shared with A360 through a one day sounding workshop. Results: Findings revealed that many local government and communal respondents do not view adolescent pregnancy as a problem, unless out of wedlock, and adolescent pregnancy is closely linked to early marriage. As a result, some providers, including HEWs, acknowledged that married adolescent girls were previously ‘neglected’ by them, while husbands indicated that they had not previously been included in FP counselling. Findings also revealed some challenges with SS implementation as HEWs were ‘deprioritizing’ the intervention and many HEWs had been in situ for several years and were overworked and frustrated. Against this backdrop, A360 was viewed as adding to the HEW workload. While the programme design was focused on adolescent users, there was increasing recognition that HEWs also needed to be at the centre of solution design. Conclusions: Despite challenges associated with the HEP, Ethiopia FP2020 plans to support the ‘next generation’ of HEWs, including a focus on adolescents and youth. To gain deeper insight and put the HEW at the centre of design, A360 will continue to work with the process evaluation to understand contextual barriers and enablers from the perspective of the HEW.
Associations of cord leptin and cord insulin with adiposity and blood pressure in White British and Pakistani children aged 4/5 years
Authors: West Jane , Santorelli Gillian , Collings Paul , Bingham Daniel , Whincup Peter , Sattar Naveed , Norris Tom , Wright John , Lawlor Debbie A. 
Published: October 2019

Background: Cord leptin and cord insulin concentrations may be important biomarkers of child adiposity and cardiovascular health, especially in populations with an increased long-term risk of type 2 diabetes and cardiovascular diseases. We aimed to determine whether cord leptin and insulin are associated with adiposity and early cardiovascular health at age 4/5, and whether any associations differ between White British and Pakistani children. Methods: Using bi-ethnic cohort data from 6060 mother-offspring pairs (2717 (44.8%) White British, 3343 (55.2%) Pakistani), we examined associations of cord leptin and insulin with adiposity (BMI, skinfold thickness) and systolic and diastolic blood pressure at age 4/5. Results: Cord leptin and insulin were higher in Pakistani compared to White British children (7.4 ng/ml versus 6.7 ng/ml and 4.1 mU/L versus 3.63 mU/L, respectively). Associations with adiposity measurements were similar in both groups and close to the null value. For example, each 10 ng/ml higher cord leptin was associated with a difference in mean childhood BMI of 0.10 kg/m2 (95% CI 0.01, 0.19) in White British, 0.01 kg/m2 (95% CI -0.08, 0.10) in Pakistani and 0.04 kg/m2 (95% CI -0.02, 0.11) in both groups combined. Associations with systolic and diastolic blood pressure were also close to the null and consistent in both groups. Conclusions: We found no evidence that cord leptin or insulin were likely to be valuable biomarkers for predicting later adiposity and blood pressure in White British or Pakistani children. For now, other factors such as family history and social-economic status may be more useful markers of risk.
Closing the Gap: A Learning Algorithm for Lost-Sales Inventory Systems with Lead Times
Authors: Zhang Huanan , Chao Xiuli , Shi Cong 
Published: October 2019

We consider a periodic-review, single-product inventory system with lost sales and positive lead times under censored demand. In contrast to the classical inventory literature, we assume the firm does not know the demand distribution a priori and makes an adaptive inventory-ordering decision in each period based only on the past sales (censored demand) data. The standard performance measure is regret, which is the cost difference between a learning algorithm and the clairvoyant (full-information) benchmark. When the benchmark is chosen to be the (full-information) optimal base-stock policy, Huh et al. [Huh WT, Janakiraman G, Muckstadt JA, Rusmevichientong P (2009a) An adaptive algorithm for finding the optimal base-stock policy in lost sales inventory systems with censored demand. Math. Oper. Res. 34(2):397–416.] developed a nonparametric learning algorithm with a cubic-root convergence rate on regret. An important open question is whether there exists a nonparametric learning algorithm whose regret rate matches the theoretical lower bound of any learning algorithms. In this work, we provide an affirmative answer to this question. More precisely, we propose a new nonparametric algorithm termed the simulated cycle-update policy and establish a square-root convergence rate on regret, which is proven to be the lower bound of any learning algorithm. Our algorithm uses a random cycle-updating rule based on an auxiliary simulated system running in parallel and also involves two new concepts, namely the withheld on-hand inventory and the double-phase cycle gradient estimation. The techniques developed are effective for learning a stochastic system with complex system dynamics and lasting impact of decisions. This paper was accepted by Yinyu Ye, optimization.
Mutual Funds and Mispriced Stocks
Authors: Avramov Doron , Cheng Si , Hameed Allaudeen 
Published: October 2019

We propose a new measure of fund investment skill, active fund overpricing (AFO), encapsulating the fund’s active share of investments, the direction of fund active bets with regard to mispriced stocks, and the dispersion of mispriced stocks in the fund’s investment opportunity set. We find that fund activeness is not sufficient for outperformance: high (low) AFO funds taking active bets on the wrong (right) side of stock mispricing achieve inferior (superior) fund performance. However, high AFO funds receive higher flows during periods of high investor sentiment, when the performance–flow relation becomes weaker. This paper was accepted by Karl Diether, finance.
Viability and gene transcription of Campylobacter jejuni in infant milk formulas
Authors: De Melo Roberta Torres , Pacheco Carla Ribeiro , Monteiro Guilherme Paz , Paiva Maia Yara Cristina , Mendonça Eliane Pereira , Braz Raquelline Figueiredo , Valadares Júnior Edson Campos , Rossi Daise Aparecida 
Published: October 2019

This study simulated the contamination of two varieties of infant milk formulas (homemade and commercial) with 103 and 104 CFU/mL of Campylobacter jejuni, that were kept under refrigeration (4-7ºC) for up to 48 hours. The aim of this study was to verify the maintenance of the viability and ability of Campylobacter jejuni to produce transcripts of virulence and resistance to stress conditions during periods of 0 (after preparation), 24 and 48 hours. C. jejuni remained viable during all analyzed stages and the presence of coliforms was not detected. In general, the counts reduced 1 log cycle after 48 hours for all samples, except the 104 CFU/mL inoculum of commercial formula, which reduced 2 log cycles, indicating greater injury of C. jejuni in this food matrix. C. jejuni showed to be more adapted to homemade matrix, due to high transcription of the gene related to cell invasion, ciaB, and more susceptible in the commercial matrix, due to the high transcription of genes related to conditions of stress tolerance (dnaJ, p19, sodB). The low infective dose of C. jejuni coupled with greater vulnerability of children less than five years indicate the need for care in the preparation and maintenance of infant formulas, to prevent the use of contaminated raw material and cross-contamination, especially in homemade formulations.
Vegetative growth and yield of robusta coffee genotypes cultivated under different shading levels
Authors: Venancio Luan Peroni , Do Amaral José Francisco Teixeira , Cavatte Paulo Cezar , Vargas Cynthia Teixeira , Dos Reis Edvaldo Fialho , Dias Jocione Ribeiro 
Published: October 2019

The growing in shaded systems is one of the strategies adopted to mitigate the impacts of climate change on coffee trees. However, there are few studies about the effect of shading on the growth and production of clones of robusta coffee (Coffea canephora). Besides that, exist a paradigm in Brazil of that the shading in coffee robusta is synonymous of less yield. Thus, the aim of this work was to evaluate whether C. canephora genotypes subjected to shading increase their yield and growth vegetative under field conditions. The study was performed between September 2013 and July 2017 (four harvests) in Alegre, Espírito Santo state, Brazil. Three genotypes of cultivar Conilon Vitória - Incaper 8142 were evaluated (03V, 06V, and 12V) and four levels of shade: full sunlight (witness) and, low, moderate and, high shade, with 38, 48 and, 68% of real capacity of shade, respectively. The shade was performed using black polyolefin screens; plants growing in full sunlight were only fenced. The tested shade levels affected the growth rate and yield of Robusta coffee plants. The shading caused a greater leaf expansion as compared to the full sunlight, as well as greater etiolation of the plagiotropic and orthotropic branches. The genotype 06V was shown to be responsive to shading, with a statistically equal production independently of shade level. The low, moderate, and high shade levels affected negatively the yield of genotypes 03V and 12V. The shading can improve the yield of Robusta coffee, in this case, of the genotype 06V of the cultivar Conilon Vitória - Incaper 8142. The success of shaded plantations depends the choice of the shade responsive genotypes and appropriate shading level.
GÊNERO ORAL BENZEÇÃO
Authors: Felix Regina Lucia , Goulart Claudia 
Published: October 2019

Esta pesquisa tem por objetivo caracterizar e analisar o gênero benzeção na atualidade, prática discursiva dos benzedores como um elemento historicamente específico de uma prática social milenar, de alguém que fala em nome de uma religião, com o intuito de curar com base na fé cristã. O corpus foi constituído de quinze benzeções coletadas na cidade de Patrocínio-MG. Os pressupostos teóricos da análise são da Linguística Textual e os critérios adotados para a caracterização desse gênero foram ancorados na teoria de Travaglia (2007), que aponta cinco parâmetros de análise: o conteúdo temático, a estrutura composicional, os objetivos e funções sociocomunicativas, as características da superfície linguística e as condições de produção do gênero. Trabalhamos com a hipótese de que há pontos divergentes nas benzeções para um mesmo problema. Os resultados das análises revelam que embora haja pontos divergentes entre os benzedores na realização do gênero, isso não impede que ele se realize. Apesar das diferenças de estilo no momento da realização do gênero, em decorrência do nível de escolaridade e da movência dos benzedores no campo das vivências socioculturais, das crenças religiosas e da variação de estilos no momento da realização do gênero, a maneira de benzer é uma só.
Training student writers in conducting peer feedback in L2 writing: A meaning-making perspective
Authors: Zhang Xiaodong , Yu Shulin 
Published: October 2019

Abstract
This study investigates how L2 (second language) student writers responded to SFL (systemic functional linguistics)-based training that was designed to assist them in harnessing meaning-making knowledge to evaluate their classmates’ essays. Conducted in a Chinese college expository writing course and based on qualitative analyses of three students’ interviews, their written feedback, as well as their reflections over one semester, the study shows that the students’ adjustment to the training occurred in a dynamic and interrelated manner. That is, along with constant teacher support and their increased knowledge gained from SFL-based training, the students transcended the limitations of their prior knowledge, which merely entailed giving feedback at the level of structural accuracy in L2 writing. They were able to gradually embrace meaning-making knowledge, although not yet fully developed. With this knowledge, they evaluated their classmates’ essays to determine if the writing content fitted the demands of valued academic compositions, such as whether and how the grammar and vocabulary were used correctly in context.