bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longer breastfeeding duration reduces the positive relationships among gestational weight gain, birth weight and childhood anthropometrics
Authors: Zhu Yeyi , Hernandez Ladia M , Dong Yongquan , Himes John H , Hirschfeld Steven , Forman Michele R 
Published: February 2015

BackgroundThe relationship between gestational weight gain (GWG) and childhood growth remains controversial. An examination on whether infant feeding practices mediate this relationship may improve our understanding of it.MethodsWe investigated whether the relationships among GWG, birth weight and childhood anthropometrics were mediated through infant feeding practices (breastfeeding duration and age at introduction of solid foods) in a cross-sectional multiethnic study of 1387 mothers and their children aged 0–5.9 years in the USA (2011–2012). Child anthropometrics included age-specific and sex-specific z-scores for weight-for-age (WAZ), height/length-for-age (HAZ), weight-for-height/length (WHZ) and body mass index-for-age (BMIZ); and ulnar length, a marker for limb growth. We used structural equation modelling to calculate standardised path coefficients and total, direct and indirect associations of GWG, birth weight and infant feeding practices with child anthropometrics.ResultsMaternal GWG had a positive indirect association with all anthropometrics mediated via birth weight, whereas longer breastfeeding duration reduced the positive associations of GWG and birth weight with WAZ, WHZ and BMIZ in non-Hispanics (β=−0.077, −0.064 and −0.106, respectively). Longer breastfeeding duration and introducing solid foods at a later age were positively associated with ulnar length (β=0.023 and 0.030, respectively) but not HAZ, suggesting a distinct association, for the first time, with limb growth.ConclusionsFindings suggest that promoting longer breastfeeding duration among women with excessive GWG who had high birthweight newborns may mitigate the potential for their offspring to develop obesity. In addition, findings reinforce the importance of promoting appropriate GWG and preventing high birth weight, which are positively associated with childhood anthropometrics.
Recurrent miscarriage: causes, evaluation and management
Authors: Garrido-Gimenez Carmen , Alijotas-Reig Jaume 
Published: February 2015

ABSTRACT
Recurrent miscarriage is frustrating for the physician and a heartbreaking experience for the patient. Approximately 5% of couples trying to conceive have two consecutive miscarriages. Despite a thorough study of patients, the aetiology of this common obstetric complication is unknown in 50% of cases. Known causes include abnormal chromosomes, endocrinological disorders and uterine abnormalities. Although antiphospholipid antibodies have been demonstrated in miscarriages, the role played by alloimmune mechanisms remains unclear. New immunological approaches such as natural killer cells, regulatory T cells, tumour necrosis factor α, cell-derived microparticles, leptin, certain glycoproteins and cytokines should be considered. The management of thyroid diseases and immunological disorders is continuously evolving. Several genetic diagnostic procedures such as parental karyotyping and preimplantation genetic screening should probably not be used routinely. Antiphopholipid syndrome and some recurrent miscarriage-related endocrinological disorders can be effectively treated. Finally, new therapeutic approaches and the pleiotropic effects of old ones have led to improved fetal–maternal outcomes.
Quantitative parameter of risk perception: can we measure a geoethic and socio-economic component in disaster vulnerability?
Authors: Kostyuchenko Yuriy V. , Movchan Dmytro 
Published: February 2015

Abstract
This paper is dedicated to the study of risk perception issues. A formal algorithm for the quantitative analysis of social factors of disaster risk is proposed. A modified form of the damage function based on the prospect theory and decision making under uncertainty due to cognitive bias and the handling of risk is proposed. Relationships for analysis of the most probable damage according to age, education and income of the population are proposed. Using multi-source statistics, the interconnected influence of education and long-term experience (education function) on the one hand, and short-term information (risk perception function) on the other hand to develop the damage function as a measure of vulnerability toward disasters has been demonstrated. As the result of the data analysis demonstrates, up to half of the damage function might be caused by social factors: education, long-term experience and responsible behaviour of information agents. It was concluded that public efforts based on ethical principles and directed toward empowering people and developing the human capacity through education can have a positive response in reducing vulnerability and enhancing the adaptive capacity toward the disasters including climate-related threats.
The L'Aquila trial
Authors: Cocco Massimo , Cultrera Giovanna , Amato Alessandro , Braun Thomas , Cerase Andrea , Margheriti Lucia , Bonaccorso Alessandro , Demartin Martina , De Martini Paolo Marco , Galadini Fabrizio , Meletti Carlo , Nostro Concetta , Pacor Francesca , Pantosti Daniela , Pondrelli Silvia , Quareni Francesca , Todesco Micol 
Published: February 2015

Abstract
The first stage of the trial in L'Aquila (Italy) ended with a conviction of seven experts, convened by the head of Civil Protection on 31 March 2009, for multiple manslaughter and serious injuries. They were sentenced to six years in jail, perpetual interdiction from public office and a fine of several million euros to be paid to the victims of the earthquake of 6 April 2009 (moment magnitude 6.3) for having caused, by their negligent conduct, the death of 29 persons and the injury of several others. The verdict had a tremendous impact on the scientific community and on the way scientists deliver their expert opinions to decision makers and society. This paper analyses the scientific argumentations reported in the Verdict Motivations, where scientific data and results were largely debated and misused to demonstrate that they should have been considered as a tool to predict an impending large earthquake. Moreover, we show that the supposed message of reassurance was not generated at the experts’ meeting or by the official Istituto Nazionale di Geofisica e Vulcanologia reports. The media had a key role in conveying information during the seismic swarm, contributing to the risk perception. We stress that prevention actions based on seismic hazard knowledge are the best defence against earthquakes.
A geoethical approach to industrial development of georesources and groundwater use: the Indian experience
Authors: Limaye Shrikant Daji 
Published: February 2015

Abstract
Geoethics is a new branch of geosciences, which is located at the meeting point of geology, philosophy, sociology, economics and ecology. In the past hundred years or so, the human footprints on the natural ecosystems are constantly getting larger and more detrimental. The development of natural resources, such as minerals and water, has certainly contributed to the economic progress of many developed and low-income nations but it has also caused degradation of the ecosystem. The sustainable use of natural resources or the eco-friendly and socio-friendly use of natural resources to ensure a long-term assurance of ecosystem services is a recent thought, which is the foundation of observing geoethics. This paper takes an overview of geoethical principles and discusses their application at the field level while developing groundwater or mineral resources. Although the paper is based on the author's experience in India, the methods are equally applicable in other low-income countries faced with the problem of balancing industrial and agricultural development with environmental protection.
Simple geoethics: an essay on daily Earth science
Authors: Bohle Martin 
Published: February 2015

Abstract
As research into the functioning of Earth, Earth sciences concern many subjects that influence the everyday dealings of the general population. However, these subjects often pass unnoticed and people have little chance to consider how these subjects intersect with their daily lives, thus, limiting their opportunities to develop informed insights regarding humankind's position within Earth's systems. To overcome this limitation, Earth science storylines should be part of the general public discourse, as meteorology experiences have been for some time. As examples can show, many opportunities for ‘telling Earth science storylines’ exist, including the use of social media for outreach activities. Earth science specialists should tell ‘Earth science storylines’ inspired by the founding scientists of geosciences who in their time were often called ‘physical geographers’.
Genetic and Pharmacological Screens Converge in Identifying FLIP, BCL2, and IAP Proteins as Key Regulators of Sensitivity to the TRAIL-Inducing Anticancer Agent ONC201/TIC10
Authors: Allen Joshua E. , Prabhu Varun V. , Talekar Mala , van den Heuvel A. Pieter J. , Lim Bora , Dicker David T. , Fritz Jennifer L. , Beck Adam , El-Deiry Wafik S. 
Published: February 2015

Abstract
ONC201/TIC10 is a small-molecule inducer of the TRAIL gene under current investigation as a novel anticancer agent. In this study, we identify critical molecular determinants of ONC201 sensitivity offering potential utility as pharmacodynamic or predictive response markers. By screening a library of kinase siRNAs in combination with a subcytotoxic dose of ONC201, we identified several kinases that ablated tumor cell sensitivity, including the MAPK pathway–inducer KSR1. Unexpectedly, KSR1 silencing did not affect MAPK signaling in the presence or absence of ONC201, but instead reduced expression of the antiapoptotic proteins FLIP, Mcl-1, Bcl-2, cIAP1, cIAP2, and survivin. In parallel to this work, we also conducted a synergy screen in which ONC201 was combined with approved small-molecule anticancer drugs. In multiple cancer cell populations, ONC201 synergized with diverse drug classes, including the multikinase inhibitor sorafenib. Notably, combining ONC201 and sorafenib led to synergistic induction of TRAIL and its receptor DR5 along with a potent induction of cell death. In a mouse xenograft model of hepatocellular carcinoma, we demonstrated that ONC201 and sorafenib cooperatively and safely triggered tumor regressions. Overall, our results established a set of determinants for ONC201 sensitivity that may predict therapeutic response, particularly in settings of sorafenib cotreatment to enhance anticancer responses. Cancer Res; 75(8); 1668–74. ©2015 AACR.
Fearful Symmetry: Subversion of Asymmetric Division in Cancer Development and Progression
Authors: Bajaj Jeevisha , Zimdahl Bryan , Reya Tannishtha 
Published: February 2015

Abstract
Asymmetric division is an evolutionarily conserved process that generates daughter cells with different fates through the unequal partitioning of fate determinants. While asymmetric division is critically important in generating diversity during development, its dysregulation can also promote oncogenesis. In particular, signals that shift the normal balance of symmetric and asymmetric division can lead to a differentiation arrest and trigger cancer progression. Here, we discuss the studies that have provided increasing support for this idea. Beginning with original work carried out in Drosophila, we trace more recent work in mammalian systems that suggest that the subversion of asymmetric division can contribute significantly to the development and progression of both hematologic malignancies and solid cancers. Cancer Res; 75(5); 792–7. ©2015 AACR.
Lung Master Protocol (Lung-MAP)—A Biomarker-Driven Protocol for Accelerating Development of Therapies for Squamous Cell Lung Cancer: SWOG S1400
Authors: Herbst Roy S. , Gandara David R. , Hirsch Fred R. , Redman Mary W. , LeBlanc Michael , Mack Philip C. , Schwartz Lawrence H. , Vokes Everett , Ramalingam Suresh S. , Bradley Jeffrey D. , Sparks Dana , Zhou Yang , Miwa Crystal , Miller Vincent A. , Yelensky Roman , Li Yali , Allen Jeff D. , Sigal Ellen V. , Wholley David , Sigman Caroline C. , Blumenthal Gideon M. , Malik Shakun , Kelloff Gary J. , Abrams Jeffrey S. , Blanke Charles D. , Papadimitrakopoulou Vassiliki A. 
Published: February 2015

Abstract
The Lung Master Protocol (Lung-MAP, S1400) is a groundbreaking clinical trial designed to advance the efficient development of targeted therapies for squamous cell carcinoma (SCC) of the lung. There are no approved targeted therapies specific to advanced lung SCC, although The Cancer Genome Atlas project and similar studies have detected a significant number of somatic gene mutations/amplifications in lung SCC, some of which are targetable by investigational agents. However, the frequency of these changes is low (5%–20%), making recruitment and study conduct challenging in the traditional clinical trial setting. Here, we describe our approach to development of a biomarker-driven phase II/II multisubstudy “Master Protocol,” using a common platform (next-generation DNA sequencing) to identify actionable molecular abnormalities, followed by randomization to the relevant targeted therapy versus standard of care. Clin Cancer Res; 21(7); 1514–24. ©2015 AACR.
LncRNA Expression Discriminates Karyotype and Predicts Survival in B-Lymphoblastic Leukemia
Authors: Fernando Thilini R. , Rodriguez-Malave Norma I. , Waters Ella V. , Yan Weihong , Casero David , Basso Giuseppe , Pigazzi Martina , Rao Dinesh S. 
Published: February 2015

Abstract
Long noncoding RNAs (lncRNA) have been found to play a role in gene regulation with dysregulated expression in various cancers. The precise role that lncRNA expression plays in the pathogenesis of B-acute lymphoblastic leukemia (B-ALL) is unknown. Therefore, unbiased microarray profiling was performed on human B-ALL specimens, and it was determined that lncRNA expression correlates with cytogenetic abnormalities, which was confirmed by qRT-PCR in a large set of B-ALL cases. Importantly, high expression of BALR-2 correlated with poor overall survival and diminished response to prednisone treatment. In line with a function for this lncRNA in regulating cell survival, BALR-2 knockdown led to reduced proliferation, increased apoptosis, and increased sensitivity to prednisolone treatment. Conversely, overexpression of BALR-2 led to increased cell growth and resistance to prednisone treatment. Interestingly, BALR-2 expression was repressed by prednisolone treatment and its knockdown led to upregulation of the glucocorticoid response pathway in both human and mouse B cells. Together, these findings indicate that BALR-2 plays a functional role in the pathogenesis and/or clinical responsiveness of B-ALL, and that altering the levels of particular lncRNAs may provide a future direction for therapeutic development.
Implications: lncRNA expression has the potential to segregate the common subtypes of B-ALL, predict the cytogenetic subtype, and indicate prognosis. Mol Cancer Res; 13(5); 839–51. ©2015 AACR.
Lack of Effect of Metformin on Mammary Carcinogenesis in Nondiabetic Rat and Mouse Models
Authors: Thompson Matthew D. , Grubbs Clinton J. , Bode Ann M. , Reid Joel M. , McGovern Renee , Bernard Philip S. , Stijleman Inge J. , Green Jeffrey E. , Bennett Christina , Juliana M. Margaret , Moeinpour Fariba , Steele Vernon E. , Lubet Ronald A. 
Published: February 2015

Abstract
Epidemiologic studies have shown that diabetics receiving the biguanide metformin, as compared with sulfonylureas or insulin, have a lower incidence of breast cancer. Metformin increases levels of activated AMPK (AMP-activated protein kinase) and decreases circulating IGF-1; encouraging its potential use in both cancer prevention and therapeutic settings. In anticipation of clinical trials in nondiabetic women, the efficacy of metformin in nondiabetic rat and mouse mammary cancer models was evaluated. Metformin was administered by gavage or in the diet, at a human equivalent dose, in standard mammary cancer models: (i) methylnitrosourea (MNU)-induced estrogen receptor–positive (ER+) mammary cancers in rats, and (ii) MMTV-Neu/p53KO ER− (estrogen receptor–negative) mammary cancers in mice. In the MNU rat model, metformin dosing (150 or 50 mg/kg BW/d, by gavage) was ineffective in decreasing mammary cancer multiplicity, latency, or weight. Pharmacokinetic studies of metformin (150 mg/kg BW/d, by gavage) yielded plasma levels (Cmax and AUC) higher than humans taking 1.5 g/d. In rats bearing small palpable mammary cancers, short-term metformin (150 mg/kg BW/d) treatment increased levels of phospho-AMPK and phospho-p53 (Ser20), but failed to reduce Ki67 labeling or expression of proliferation-related genes. In the mouse model, dietary metformin (1,500 mg/kg diet) did not alter final cancer incidence, multiplicity, or weight. Metformin did not prevent mammary carcinogenesis in two mammary cancer models, raising questions about metformin efficacy in breast cancer in nondiabetic populations. Cancer Prev Res; 8(3); 231–9. ©2015 AACR.
Prevention of Tumor Growth Driven by PIK3CA and HPV Oncogenes by Targeting mTOR Signaling with Metformin in Oral Squamous Carcinomas Expressing OCT3
Authors: Madera Dmitri , Vitale-Cross Lynn , Martin Daniel , Schneider Abraham , Molinolo Alfredo A. , Gangane Nitin , Carey Thomas E. , McHugh Jonathan B. , Komarck Christine M. , Walline Heather M. , William William N. , Seethala Raja R. , Ferris Robert L. , Gutkind J. Silvio 
Published: February 2015

Abstract
Most squamous cell carcinomas of the head and neck (HNSCC) exhibit a persistent activation of the PI3K–mTOR signaling pathway. We have recently shown that metformin, an oral antidiabetic drug that is also used to treat lipodystrophy in HIV-infected (HIV+) individuals, diminishes mTOR activity and prevents the progression of chemically induced experimental HNSCC premalignant lesions. Here, we explored the preclinical activity of metformin in HNSCCs harboring PIK3CA mutations and HPV oncogenes, both representing frequent HNSCC alterations, aimed at developing effective targeted preventive strategies. The biochemical and biologic effects of metformin were evaluated in representative HNSCC cells expressing mutated PIK3CA or HPV oncogenes (HPV+). The oral delivery of metformin was optimized to achieve clinical relevant blood levels. Molecular determinants of metformin sensitivity were also investigated, and their expression levels were examined in a large collection of HNSCC cases. We found that metformin inhibits mTOR signaling and tumor growth in HNSCC cells expressing mutated PIK3CA and HPV oncogenes, and that these activities require the expression of organic cation transporter 3 (OCT3/SLC22A3), a metformin uptake transporter. Coexpression of OCT3 and the mTOR pathway activation marker pS6 were observed in most HNSCC cases, including those arising in HIV+ patients. Activation of the PI3K–mTOR pathway is a widespread event in HNSCC, including HPV− and HPV+ lesions arising in HIV+ patients, all of which coexpress OCT3. These observations may provide a rationale for the clinical evaluation of metformin to halt HNSCC development from precancerous lesions, including in HIV+ individuals at risk of developing HPV− associated cancers. Cancer Prev Res; 8(3); 197–207. ©2015 AACR.
Common Genetic Variants and Response to Atrial Fibrillation Ablation
Authors: Shoemaker M. Benjamin , Bollmann Andreas , Lubitz Steven A. , Ueberham Laura , Saini Harsimran , Montgomery Jay , Edwards Todd , Yoneda Zachary , Sinner Moritz F. , Arya Arash , Sommer Philipp , Delaney Jessica , Goyal Sandeep K. , Saavedra Pablo , Kanagasundram Arvindh , Whalen S. Patrick , Roden Dan M. , Hindricks Gerhard , Ellis Christopher R. , Ellinor Patrick T. , Darbar Dawood , Husser Daniela 
Published: February 2015

Background—

Common single nucleotide polymorphisms (SNPs) at chromosomes 4q25 (rs2200733, rs10033464 near
PITX2
), 1q21 (rs13376333 in
KCNN3
), and 16q22 (rs7193343 in
ZFHX3
) have consistently been associated with the risk of atrial fibrillation (AF). Single-center studies have shown that 4q25 risk alleles predict recurrence of AF after catheter ablation of AF. Here, we performed a meta-analysis to test the hypothesis that these 4 AF susceptibility SNPs modulate response to AF ablation.

Methods and Results—

Patients underwent de novo AF ablation between 2008 and 2012 at Vanderbilt University, the Heart Center Leipzig, and Massachusetts General Hospital. The primary outcome was 12-month recurrence, defined as an episode of AF, atrial flutter, or atrial tachycardia lasting >30 seconds after a 3-month blanking period. Multivariable analysis of the individual cohorts using a Cox proportional hazards model was performed. Summary statistics from the 3 centers were analyzed using fixed effects meta-analysis. A total of 991 patients were included (Vanderbilt University, 245; Heart Center Leipzig, 659; and Massachusetts General Hospital, 87). The overall single procedure 12-month recurrence rate was 42%. The overall risk allele frequency for these SNPs ranged from 12% to 35%. Using a dominant genetic model, the 4q25 SNP, rs2200733, predicted a 1.4-fold increased risk of recurrence (adjusted hazard ratio,1.3 [95% confidence intervals, 1.1–1.6];
P
=0.011). The remaining SNPs, rs10033464 (4q25), rs13376333 (1q21), and rs7193343 (16q22) were not significantly associated with recurrence.

Conclusions—
Among the 3 genetic loci most strongly associated with AF, the chromosome 4q25 SNP rs2200733 is significantly associated with recurrence of atrial arrhythmias after catheter ablation for AF.
Effect of Catheter Ablation and Periprocedural Anticoagulation Regimen on the Clinical Course of Migraine in Atrial Fibrillation Patients With or Without Pre-Existent Migraine
Authors: Mohanty Sanghamitra , Mohanty Prasant , Rutledge J. Neal , Di Biase Luigi , Yan Rachel Xue , Trivedi Chintan , Santangeli Pasquale , Bai Rong , Cardinal Deb , Burkhardt J. David , Gallinghouse Joseph G. , Horton Rodney , Sanchez Javier E. , Bailey Shane , Hranitzky Patrick M. , Zagrodzky Jason , Al-Ahmad Amin , Natale Andrea 
Published: February 2015

Background—
We examined the influence of catheter ablation and periprocedural anticoagulation regimen on trajectory of migraine in atrial fibrillation patients with or without migraine history.

Methods and Results—

Forty patients with (group 1: 64±8 years; men 78%) and 85 (group 2: 61±10 years; men 73%) without migraine history undergoing atrial fibrillation-ablation were enrolled. Migraine status and quality of life were evaluated using standardized questionnaires. Diffusion magnetic resonance imaging of brain was performed for all at pre and 24 hours post procedure. Catheter ablation was performed with (88, 70%) or without (37, 30%) continuous warfarin treatment. Fifty-four patients (11 and 43 from groups 1 and 2, respectively) had subtherapeutic international normalized ratio on procedure day. At 17±5 months follow-up, from group 1, 25 (63%) reported no migraine, 10 (25%) had <1, and 3 (8%) had 2 to 3 monthly symptoms. Intensity of pain decreased from baseline 7 (Q1–Q3, 4–8) to 2 (0–4) scale points at follow-up (
P
<0.001) and duration of headache from median 8 (Q1–Q3, 4–15) to 0.5 (Q1–Q3, 0–2) hours (
P
<0.001). Two patients from group 1 reported increased migraine severity and 2 from group 2 had new-onset migraine. Follow-up diffusion magnetic resonance imaging revealed new infarcts in 9.6% (12/125) patients; of which 11 had subtherapeutic preprocedural international normalized ratio on or off continuous warfarin. Quality of life improved significantly in patients with successful ablation, being more pronounced in group 1.

Conclusions—
In most patients, migraine symptoms improved substantially after catheter ablation. Interestingly, the only cases of new migraine and aggravation of pre-existent headache had subtherapeutic international normalized ratio during the procedure and new cerebral infarcts.