bluuebunny/crossref_metadata_2025_split huggingface dataset:
Programmed Cell Death 1 (PD-1) Ligand (PD-L1) Expression in Solid Tumors As a Predictive Biomarker of Benefit From PD-1/PD-L1 Axis Inhibitors: A Systematic Review and Meta-Analysis
Authors: Khunger Monica , Hernandez Adrian V. , Pasupuleti Vinay , Rakshit Sagar , Pennell Nathan A. , Stevenson James , Mukhopadhyay Sanjay , Schalper Kurt , Velcheti Vamsidhar 
Published: July 2017

Purpose Drugs targeting the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway show significant clinical activity across several tumor types. However, a majority of patients do not respond to these agents. Use of biomarker assays to predict response to these agents is an active area of research; however, the predictive value of PD-L1 immunohistochemistry (IHC) assays is largely inconsistent across clinical trials. In this meta-analysis of clinical trials of PD-1/PD-L1–targeted agents, we evaluate the predictive value of a tumor and tumor-infiltrating immune cell PD-L1 IHC assay as a biomarker for objective response to PD-1/PD-L1 inhibitors. Methods We searched databases (PubMed, Medline, ASCO abstracts, European Society for Medical Oncology abstracts, and Scopus) up until December 2016 for clinical trials using PD-1/PD-L1 inhibitors with reported PD-L1 biomarker data. Objective response rates (primary end point) from all phase I to III trials investigating nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab in advanced solid tumors were collected. Odds ratios (ORs) for response in PD-L1–positive patients compared with PD-L1–negative patients were calculated using the DerSimonian-Laird random effects model to combine trials. We performed meta-analysis as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results Forty-one distinct trials with 6,664 patients were identified. PD-L1 expression was predictive of favorable response across all tumor types (OR, 2.26; 95% CI, 1.85 to 2.75; P < .001), with the significantly largest effect observed in non–small-cell lung cancer (OR, 2.51; 95% CI, 1.99 to 3.17; P < .001). A subgroup analysis across all non–small-cell lung cancer trials using nivolumab and Dako clone 28-8 (Dako, Carpinteria, CA) IHC antibody assay yielded a significantly higher objective response rate in patients with tumor PD-L1 expression even at the minimum cutoff value of 1% (OR, 2.17; 95% CI, 1.03 to 4.57). Conclusion Our meta-analysis shows that tumor and tumor-infiltrating immune cell PD-L1 overexpression based on IHC is associated with significantly higher response rates to PD-1/PD-L1 axis inhibitors across a range of malignant solid tumors.
OncoKB: A Precision Oncology Knowledge Base
Authors: Chakravarty Debyani , Gao Jianjiong , Phillips Sarah , Kundra Ritika , Zhang Hongxin , Wang Jiaojiao , Rudolph Julia E. , Yaeger Rona , Soumerai Tara , Nissan Moriah H. , Chang Matthew T. , Chandarlapaty Sarat , Traina Tiffany A. , Paik Paul K. , Ho Alan L. , Hantash Feras M. , Grupe Andrew , Baxi Shrujal S. , Callahan Margaret K. , Snyder Alexandra , Chi Ping , Danila Daniel C. , Gounder Mrinal , Harding James J. , Hellmann Matthew D. , Iyer Gopa , Janjigian Yelena Y. , Kaley Thomas , Levine Douglas A. , Lowery Maeve , Omuro Antonio , Postow Michael A. , Rathkopf Dana , Shoushtari Alexander N. , Shukla Neerav , Voss Martin H. , Paraiso Ederlinda , Zehir Ahmet , Berger Michael F. , Taylor Barry S. , Saltz Leonard B. , Riely Gregory J. , Ladanyi Marc , Hyman David M. , Baselga José , Sabbatini Paul , Solit David B. , Schultz Nikolaus 
Published: July 2017

Purpose With prospective clinical sequencing of tumors emerging as a mainstay in cancer care, an urgent need exists for a clinical support tool that distills the clinical implications associated with specific mutation events into a standardized and easily interpretable format. To this end, we developed OncoKB, an expert-guided precision oncology knowledge base. Methods OncoKB annotates the biologic and oncogenic effects and prognostic and predictive significance of somatic molecular alterations. Potential treatment implications are stratified by the level of evidence that a specific molecular alteration is predictive of drug response on the basis of US Food and Drug Administration labeling, National Comprehensive Cancer Network guidelines, disease-focused expert group recommendations, and scientific literature. Results To date, > 3,000 unique mutations, fusions, and copy number alterations in 418 cancer-associated genes have been annotated. To test the utility of OncoKB, we annotated all genomic events in 5,983 primary tumor samples in 19 cancer types. Forty-one percent of samples harbored at least one potentially actionable alteration, of which 7.5% were predictive of clinical benefit from a standard treatment. OncoKB annotations are available through a public Web resource ( http://oncokb.org ) and are incorporated into the cBioPortal for Cancer Genomics to facilitate the interpretation of genomic alterations by physicians and researchers. Conclusion OncoKB, a comprehensive and curated precision oncology knowledge base, offers oncologists detailed, evidence-based information about individual somatic mutations and structural alterations present in patient tumors with the goal of supporting optimal treatment decisions.
Prospective Genomic Profiling of Prostate Cancer Across Disease States Reveals Germline and Somatic Alterations That May Affect Clinical Decision Making
Authors: Abida Wassim , Armenia Joshua , Gopalan Anuradha , Brennan Ryan , Walsh Michael , Barron David , Danila Daniel , Rathkopf Dana , Morris Michael , Slovin Susan , McLaughlin Brigit , Curtis Kristen , Hyman David M. , Durack Jeremy C. , Solomon Stephen B. , Arcila Maria E. , Zehir Ahmet , Syed Aijazuddin , Gao Jianjiong , Chakravarty Debyani , Vargas Hebert Alberto , Robson Mark E. , Vijai Joseph , Offit Kenneth , Donoghue Mark T.A. , Abeshouse Adam A. , Kundra Ritika , Heins Zachary J. , Penson Alexander V. , Harris Christopher , Taylor Barry S. , Ladanyi Marc , Mandelker Diana , Zhang Liying , Reuter Victor E. , Kantoff Philip W. , Solit David B. , Berger Michael F. , Sawyers Charles L. , Schultz Nikolaus , Scher Howard I. 
Published: July 2017

Purpose A long natural history and a predominant osseous pattern of metastatic spread are impediments to the adoption of precision medicine in patients with prostate cancer. To establish the feasibility of clinical genomic profiling in this disease, we performed targeted deep sequencing of tumor and normal DNA from patients with locoregional, metastatic noncastrate, and metastatic castration-resistant prostate cancer. Patients and Methods Patients consented to genomic analysis of their tumor and germline DNA. A hybridization capture-based clinical assay was used to identify single-nucleotide variations, small insertions and deletions, copy number alterations, and structural rearrangements in more than 300 cancer-related genes in tumors and matched normal blood. Results We successfully sequenced 504 tumors from 451 patients with prostate cancer. Potentially actionable alterations were identified in DNA damage repair, phosphatidylinositol 3-kinase, and mitogen-activated protein kinase pathways. Twenty-seven percent of patients harbored a germline or a somatic alteration in a DNA damage repair gene that may predict for response to poly (ADP-ribose) polymerase inhibition. Profiling of matched tumors from individual patients revealed that somatic TP53 and BRCA2 alterations arose early in tumors from patients who eventually developed metastatic disease. In contrast, comparative analysis across disease states revealed that APC alterations were enriched in metastatic tumors, whereas ATM alterations were specifically enriched in castration-resistant prostate cancer. Conclusion Through genomic profiling of prostate tumors that represent the disease clinical spectrum, we identified a high frequency of potentially actionable alterations and possible drivers of disease initiation, metastasis, and castration resistance. Our findings support the routine use of tumor and germline DNA profiling for patients with advanced prostate cancer for the purpose of guiding enrollment in targeted clinical trials and counseling families at increased risk of malignancy.
What influences women to bottle-feed from birth and to discontinue breastfeeding early?
Authors: Goncalves Andreia VAS 
Published: July 2017

Background Internationally, breast milk is recognised as the best form of infant feeding, yet in the UK, bottle feeding rates are among the highest in the world. Aims The aim of this research study was to investigate the relationship between socioeconomic, demographic, family-related, pregnancy and birth factors, and bottle feeding in the UK. Methods A secondary analysis of the Infant Feeding Survey 2010 was conducted and two time points differentiated: bottle feeding from birth and early breastfeeding cessation. Findings Results demonstrated that bottle feeding from birth was predicted by a range of independent social disadvantage factors, namely being young, single, unemployed, white British and poorly educated. Other influencing factors were the increased number of children, having a caesarean section, no underlying health problems post birth and having friends who bottle-fed. Early breastfeeding cessation was predicted by the same independent determinants except for working in intermediate or routine/manual occupations, having friends that mix-fed, and developing health problems post birth. Conclusions The context in which mothers live is a key determinant of how they feed their babies and that, for many women, feeding method is a consequence of their social context and not a choice.
Comportamento hidrodinâmico e hidroquímico do sistema aquífero Barreiras-Jandaíra-Açu na área da fazenda Belém, oeste da Bacia Potiguar, CE
Authors: Braga Junior Maurilo Gonçalves , Melo José Geraldo de , Diniz Filho José Braz 
Published: July 2017

A avaliação do comportamento hidrodinâmico e hidroquímico de aquíferos em áreas sob a influência da atividade petrolífera são essenciais para a proteção e gestão do recurso hídrico subterrâneo. Neste sentido, são analisadas neste trabalho as relações entre as cargas potenciométricas dos aquíferos Barreiras-Jandaíra e Açu na área de Fazenda Belém, oeste da Bacia sedimentar Potiguar estado do Ceará e suas implicações na qualidade das águas subterrâneas. Foram consultados trabalhos regionais e estudos específicos na área de Fazenda Belém, acerca das características hidrodinâmicas e hidroquímicas das águas dos dois sistemas Aquíferos. Foram obtidos os dados hidroquímicos e de nível estático e definidas as superfícies potenciométricas e os tipos iônicos dessas unidades aquíferas em diferentes períodos desde seu estado original, antes da influência da atividade petrolífera, até os dias atuais. O Aquífero Açu apresentou um rebaixamento da ordem de até 110m, enquanto o sistema Aquífero Barreiras-Jandaíra sobrejacente, apresentou somente pequenas variações da ordem de 2 a 4m. Os dados hidroquímicos permitem afirmar que na área de estudo, as águas armazenadas no Aquífero Barreiras-Jandaíra são classificadas como do tipo cloretada-bicarbonatada – sódica–cálcica e as águas armazenadas no Aquífero Açu são classificadas como do tipo bicarbonatada-cloretada – sódica. Foi possível concluir que os aquíferos Açu e Barreiras–Jandaíra correspondem a sistemas aquíferos individualizados. O fato de que o rebaixamento do nível estático verificado no Aquífero Açu, não afetou as cargas potenciométricas do Aquífero Barreiras-Jandaíra e os tipos iônicos distintos definidos para os dois sistemas aquíferos, sugere a existência de um isolamento hidráulico e a inexistência de mistura de águas entre os mesmos, desde seu estado original até o presente.
Increasing Block Tariffs in the Water Sector – An Interpretation in Terms of Social Preferences
Authors: Meran Georg , von Hirschhausen Christian 
Published: July 2017

AbstractMany developing countries around the world apply progressive water tariffs, often structured in the form of discretely increasing block tariffs (IBTs). These tariffs have been criticized in the welfare economic literature due to their perceived inefficiency: many of the prices charged under IBTs do not correspond to marginal costs and thus violate the principle of allocative efficiency. In this paper we explore an alternative interpretation of the widespread use of IBTs, in terms of social preferences and fairness considerations. For this, we rely on an extension of the Fehr, E., and K. Schmidt (1999. “A Theory of Fairness, Competition, and Cooperation.”Quarterly Journal of Economics114: 817–868.) utility function, including inequality aversion, to which we add another parameter representing a reference for redistribution which reflects a societal preference to correct for income difference perceived as unfair. Additionally, the model includes a variable on household size, finding that, as poor households are on average larger, a simple IBT tariff disregarding household size may not be “fair”.
Retrofitting the Low Impact Development Practices into Developed Urban areas Including Barriers and Potential Solution
Authors: Shafique Muhammad , Kim Reeho 
Published: July 2017

AbstractLow impact development (LID)/green infrastructure (GI) practices have been identified as the sustainable practices of managing the stormwater in urban areas. Due to the increasing population, most of the cities are more developing which results in the change of natural area into impervious areas (roads, buildings etc.). Moreover, urbanization and climate change are causing many water-related problems and making over cities unsafe and insecure. Under these circumstances, there is a need to introduce new stormwater management practices into developed cities to reduce the adverse impacts of urbanization. For this purpose, retrofitting low impact development practices demands more attention to reduce these water-related problems and trying to make our cities sustainable. In developed areas, there is a little space is available for the retrofitting of LID practices for the stormwater management. Therefore, the selection of an appropriate place to retrofitting LID practices needs more concern. This paper describes the successfully applied retrofitting LID practices around the globe. It also includes the process of applying retrofitting LID practices at the suitable place with the suitable combination. Optimal places for the retrofitting of different LID practices are also mentioned. This paper also highlights the barriers and potential solutions of retrofitting LID practices in urban areas.
A Novel Hybrid Technique to Predict the Lithium-Ion Battery’s Behavior and Estimate the Intern Impedance
Authors: Elabadine Dahmane Zine , Ali Malek , Mourad Haddadi 
Published: July 2017

AbstractA battery model that predicts the electrical performance with high accuracy is vital for circuit designing to control the battery usage and improve its runtime and safety in electrical systems such as electric vehicle (EV). In this paper, a relatively simple equivalent circuit based model is developed for modeling the performance of lithium ion batteries used in automotive applications. The model’s strategy adopted for characterization of the internal parameters is based on two main techniques: one is the electrochemical impedance spectroscopy (EIS) tests, where comparable circuit is set up as per EIS test perceptions and the other is the current pulses technique, this latter is carried out using a proposed current pulses profile. The extracted parameters are scheduled on the state-of-charge, temperature, and current direction. The comparison between experiment and simulation results demonstrates that with the optimally extracted performance parameters, the proposed approach can accurately predict the performance of differents batteries of various sizes, capacities, and materials. Eventually, this simple battery model can serve as a robust and reliable tool for predicting the battery’s I-V performance in electrified vehicle battery management systems.
Code-switching in the media: Identity negotiations in a Gujarati diaspora radio program
Authors: Zipp Lena 
Published: July 2017

AbstractThis article aims to explore the construction of post-diasporic, hybrid local identities in communicative practices of the younger British Gujarati community. It focuses on the host of a popular BBC Asian Network radio show as a prominent voice of this community, who simultaneously embodies and creates linguistic community values through the use of Gujarati-English code-switching. In doing so, it highlights the role of the media in shaping a space for the linguistic negotiation of local and transnational influences. On a methodological level, the article argues for the combination of data from different domains in the context of transnational identity negotiations, such as linguistic behavior, narrative language biographies, private and public meta-linguistic commentary, indications of language status and attitudes towards alternating language use.
Quintilian on “grammatical homonymy”: The linguistic sensibility of a Roman lawyer
Authors: Uría Javier 
Published: July 2017

AbstractAfter defining grammatical (as opposed to lexical) homonymy as concerning either inflection or the conflict between different parts of speech, attention is paid to those contexts in which Varro and Quintilian dealt with processes falling under that concept. The paper remarks on the acute distinction Quintilian seems to make between lexical and grammatical homonymy by dealing with the former in relation to rhetoric and the latter within the grammatical chapters of book I. The similarity of Quintilian’s approach to homonymy is then shown with the use Apollonius Dyscolus would later make of the term
De caballos voladores y formidables tempestades: Experiencias religiosas del paisaje misional en Esteco (s. XVI-XVIII) y Tierra del Fuego (s. XIX-XX)
Authors: Marschoff María , Salerno Melisa A. 
Published: July 2017

Neste trabalho, analisamos a experiência religiosa de paisagem de dois grupos missionários em contextos coloniais historicamente diferentes. O primeiro grupo é o dos jesuítas, que viajaram, viveram e fundaram reduções na jurisdição da cidade de Esteco (norte da Argentina) desde o final do século XVI até o principio do século XVIII. O segundo, corresponde aos missionários salesianos, que exploraram e estabeleceram missões na Tierra del Fuego (sul da Argentina e Chile) desde o final do século XIX até meados do século XX. No decorrer de seus trabalhos, ambas ordens produziram uma série de registros sobre eventos percebidos geralmente como conjunturais para suas vidas: “visões” da paisagem antes de chegar ao lugar, fenômenos naturais considerados catastróficos (como tempestades e terremotos de grande magnitude), situações de risco pessoal (como estar perdido na região ou encontrar-se sem recursos), epidemias e pestes, etc. Considerando essas referências, nos perguntamos sobre a relação entre a materialidade das paisagens e as experiências religiosas. Especificamente, nos indagamos como as paisagens inicialmente desconhecidaspara os missionários foram mudando sua“qualidade” religiosa ao longo da labor evangelizadora sobre os indígenas.
Spontaneous reossification of the sella in transsphenoidal reoperation associated with strontium ranelate
Authors: Pineyro Maria Mercedes , Arrestia Daiana , Elhordoy Mariana , Lima Ramiro , Wajskopf Saul , Pisabarro Raul , Serra Maria Pilar 
Published: July 2017

Summary
Spontaneous reossification of the sellar floor after transsphenoidal surgery has been rarely reported. Strontium ranelate, a divalent strontium salt, has been shown to increase bone formation, increasing osteoblast activity. We describe an unusual case of a young patient with Cushing’s disease who was treated with strontium ranelate for low bone mass who experienced spontaneous sellar reossification after transsphenoidal surgery. A 21-year-old male presented with Cushing’s features. His past medical history included delayed puberty diagnosed at 16 years, treated with testosterone for 3 years without further work-up. He was diagnosed with Cushing’s disease initially treated with transsphenoidal surgery, which was not curative. The patient did not come to follow-up visits for more than 1 year. He was prescribed strontium ranelate 2 g orally once daily for low bone mass by an outside endocrinologist, which he received for more than 1 year. Two years after first surgery he was reevaluated and persisted with active Cushing’s disease. Magnetic resonance image revealed a left 4 mm hypointense mass, with sphenoid sinus occupation by a hyperintense material. At repeated transsphenoidal surgery, sellar bone had a very hard consistency; surgery was complicated and the patient died. Sellar reossification negatively impacted surgery outcomes in this patient. While this entity is possible after transsphenoidal surgery, it remains unclear whether strontium ranelate could have affected sellar ossification.

Learning points:

Delayed puberty can be a manifestation of Cushing’s syndrome. A complete history, physical examination and appropriate work-up should be performed before initiating any treatment.

Sellar reossification should always be taken into account when considering repeated transsphenoidal surgery. Detailed preoperative evaluation of bony structures by computed tomography ought to be performed in all cases of reoperation.

We speculate if strontium ranelate may have affected bone mineralization at the sellar floor. We strongly recommend that indications for prescribing this drug should be carefully followed.