bluuebunny/crossref_metadata_2025_split huggingface dataset:
Examining the effectiveness of consuming flour made from agronomically biofortified wheat (Zincol-2016/NR-421) for improving Zn status in women in a low-resource setting in Pakistan: study protocol for a randomised, double-blind, controlled cross-over trial (BiZiFED)
Authors: Lowe Nicola M , Khan Muhammad Jaffar , Broadley Martin R , Zia Munir H , McArdle Harry J , Joy Edward J M , Ohly Heather , Shahzad Babar , Ullah Ubaid , Kabana Gul , Medhi Rashid , Afridi Mukhtiar Zaman 
Published: April 2018

IntroductionDietary zinc (Zn) deficiency is a global problem, particularly in low-income and middle-income countries where access to rich, animal-source foods of Zn is limited due to poverty. In Pakistan, Zn deficiency affects over 40% of the adult female population, resulting in suboptimal immune status and increased likelihood of complications during pregnancy.Methods and analysisWe are conducting a double-blind, randomised controlled feeding study with cross-over design in a low-resource setting in Pakistan. Households were provided with flour milled from genetically and agronomically biofortified grain (Zincol-2016/NR-421) or control grain (Galaxy-2013). Fifty households were recruited. Each household included a woman aged 16–49 years who is neither pregnant nor breastfeeding, and not currently consuming nutritional supplements. These women were the primary study participants. All households were provided with control flour for an initial 2-week baseline period, followed by an 8-week intervention period where 25 households receive biofortified flour (group A) and 25 households receive control flour (group B). After this 8-week period, groups A and B crossed over, receiving control and biofortified flour respectively for 8 weeks. Tissue (blood, hair and nails) have been collected from the women at five time points: baseline, middle and end of period 1, and middle and end of period 2.Ethics and disseminationEthical approval was granted from the lead university (reference no. STEMH 697 FR) and the collaborating institution in Pakistan. The final study methods (including any modifications) will be published in peer-reviewed journals, alongside the study outcomes on completion of the data analysis. In addition, findings will be disseminated to the scientific community via conference presentations and abstracts and communicated to the study participants through the village elders at an appropriate community forum.Registration detailsThe trial has been registered with the ISRCTN registry, study IDISRCTN83678069.
Increasing trends in hospital care burden of atrial fibrillation in Korea, 2006 through 2015
Authors: Kim Daehoon , Yang Pil-Sung , Jang Eunsun , Yu Hee Tae , Kim Tae-Hoon , Uhm Jae-Sun , Kim Jong Youn , Pak Hui-Nam , Lee Moon-Hyoung , Joung Boyoung , Lip Gregory Y H 
Published: April 2018

ObjectiveTemporal changes in the healthcare burden of atrial fibrillation (AF) are less well known in rapidly ageing Asian countries. We examined trends in hospitalisations, costs, treatment patterns and outcomes related to AF in Korea.MethodsUsing the National Health Insurance Service (NHIS) database involving the entire adult Korean population (n=41 701 269 in 2015), we analysed a nationwide AF cohort representing 931 138 patients with AF. We studied all hospitalisations due to AF from 2006 to 2015.ResultsOverall, hospitalisations for AF increased by 420% from 767 to 3986 per 1 million Korean population from 2006 to 2015. Most admissions occurred in patients aged ≥70 years, and the most frequent coexisting conditions were hypertension, heart failure and chronic obstructive pulmonary disease. Hospitalisations mainly due to major bleeding and AF control increased, whereas hospitalisations mainly due to ischaemic stroke and myocardial infarction decreased. The total cost of care increased even after adjustment for inflation from €68.4 million in 2006 to €388.4 million in 2015, equivalent to 0.78% of the Korean NHIS total expenditure. Overall in-hospital mortality decreased from 7.5% in 2006 to 4.3% in 2015. The in-hospital mortality was highest in patients ≥80 years of age (7.7%) and in patients with chronic kidney disease (7.4%).ConclusionsAF hospitalisations have increased exponentially over the past 10 years in Korea, in association with an increase in comorbid chronic diseases. Mortality associated with AF hospitalisations decreased during the last decade, but hospitalisation costs have markedly increased.
A Pan-cancer Landscape of Interactions between Solid Tumors and Infiltrating Immune Cell Populations
Authors: Tamborero David , Rubio-Perez Carlota , Muiños Ferran , Sabarinathan Radhakrishnan , Piulats Josep M. , Muntasell Aura , Dienstmann Rodrigo , Lopez-Bigas Nuria , Gonzalez-Perez Abel 
Published: April 2018

Abstract
Purpose: Throughout their development, tumors are challenged by the immune system, and they acquire features to evade its surveillance. A systematic view of these traits, which shed light on how tumors respond to immunotherapies, is still lacking.
Experimental Design: Here, we computed the relative abundance of an array of immune cell populations to measure the immune infiltration pattern of 9,174 tumors of 29 solid cancers. We then clustered tumors with similar infiltration pattern to define immunophenotypes. Finally, we identified genomic and transcriptomic traits associated to these immunophenotypes across cancer types.
Results: In highly cytotoxic immunophenotypes, we found tumors with low clonal heterogeneity enriched for alterations of genes involved in epigenetic regulation, ubiquitin-mediated proteolysis, antigen presentation, and cell–cell communication, which may drive resistance in combination with the ectopic expression of negative immune checkpoints. Tumors with immunophenotypes of intermediate cytotoxicity are characterized by an upregulation of processes involved in neighboring tissue invasion and remodeling that may foster the recruitment of immunosuppressive cells. Tumors with poorly cytotoxic immunophenotype tend to be of more advanced stages and bear a greater burden of copy number alterations and frequent alterations of cell cycle, hedgehog, β-catenin, and TGFβ pathways, which may cause immune depletion.
Conclusions: We provide a comprehensive landscape of the characteristics of solid tumors that may influence (or be influenced by) the characteristics of their immune infiltrate. These results may help interpret the response of solid tumors to immunotherapies and guide the development of novel drug combination strategies. Clin Cancer Res; 24(15); 3717–28. ©2018 AACR.
Left Ventricular Assist Device Inflow Cannula Angle and Thrombosis Risk
Authors: Chivukula Venkat Keshav , Beckman Jennifer A. , Prisco Anthony R. , Dardas Todd , Lin Shin , Smith Jason W. , Mokadam Nahush A. , Aliseda Alberto , Mahr Claudius 
Published: April 2018

Background:
As heart failure prevalence continues to increase in the setting of a static donor supply, left ventricular assist device (LVAD) therapy for end-stage heart failure continues to grow. Anecdotal evidence suggests that malalignment of the LVAD inflow cannula may increase thrombosis risk, but this effect has not been explored mechanistically or quantified statistically. Our objective is to elucidate the impact of surgical angulation of the inflow cannula on thrombogenicity.

Methods and Results:
Unsteady computational fluid dynamics is used in conjunction with computational modeling and virtual surgery to model flow through the left ventricle for 5 different inflow cannula angulations. We use a holistic approach to evaluate thrombogenicity: platelet-based (Lagrangian) metrics to evaluate the platelet mechanical environment, combined with flow-based (Eulerian) metrics to investigate intraventricular hemodynamics. The thrombogenic potential of each LVAD inflow cannula angulation is quantitatively evaluated based on platelet shear stress history and residence time. Intraventricular hemodynamics are strongly influenced by LVAD inflow cannula angulation. Platelet behavior indicates elevated thrombogenic potential for certain inflow cannula angles, potentially leading to platelet activation. Our analysis demonstrates that the optimal range of inflow angulation is within 0±7° of the left ventricular apical axis.

Conclusions:
Angulation of the inflow cannula >7° from the apical axis (axis connecting mitral valve and ventricular apex) leads to markedly unfavorable hemodynamics as determined by computational fluid dynamics. Computational hemodynamic simulations incorporating Lagrangian and Eulerian metrics are a powerful tool for studying optimization of LVAD implantation strategies, with the long-term potential of improving outcomes.
Symplocos ståhlii Kottaim., a new name for extant Symplocos globosa B.Ståhl (Symplocaceae)
Authors: KOTTAIMUTHU RAMALINGAM 
Published: April 2018

Symplocos Jacquin (1760: 24) is the largest genus in the family Symplocaceae and comprises about ca. 340 species (Fritsch et al. 2008). It is distributed in the tropical and subtropical regions of eastern and southeastern Asia, the Americas and Australia (Nooteboom 2004). The genus Symplocos Jacq. is known to have 33 species in Ecuador (Ståhl 2010; Ulloa et al. 2015), the majority of which occur in Andean forests (Ståhl 1995). While revising the genus Symplocos in Ecuador, Ståhl (1991) described 15 new species. Among these, the name S. globosa B.Ståhl (1991: 27) is illegitimate, being a later homonym (Art. 53.1 of the ICN; McNeill et al. 2012) of the fossil taxon S. globosa R. Ludwig (1857: 98). Therefore, the new name Symplocos ståhlii Kottaim. is proposed here as a replacement name for the extant S. globosa.
FACETs: A Proposed Next-Generation Paradigm for High-Impact Weather Forecasting
Authors: Rothfusz Lans P. , Schneider Russell , Novak David , Klockow-McClain Kimberly , Gerard Alan E. , Karstens Chris , Stumpf Gregory J. , Smith Travis M. 
Published: April 2018

AbstractRecommendations by the National Research Council (NRC), the National Institute of Standards and Technology (NIST), and Weather-Ready Nation workshop participants have encouraged the National Oceanic and Atmospheric Administration (NOAA) and the broader weather enterprise to explore and expand the use of probabilistic information to convey weather forecast uncertainty. Forecasting a Continuum of Environmental Threats (FACETs) is a concept being explored by NOAA to address those recommendations and also potentially shift the National Weather Service (NWS) from (primarily) teletype-era, deterministic watch–warning products to high-resolution, probabilistic hazard information (PHI) spanning periods from days (and longer) to within minutes of high-impact weather and water events. FACETs simultaneously i) considers a reinvention of the NWS hazard forecasting and communication paradigm so as to deliver multiscale, user-specific probabilistic guidance from numerical weather prediction ensembles and ii) provides a comprehensive framework to organize the physical, social, and behavioral sciences, the technology, and the practices needed to achieve that reinvention. The first applications of FACETs have focused on thunderstorm phenomena, but the FACETs concept is envisioned to extend to the attributes of any environmental hazards that can be described probabilistically (e.g., winter, tropical, and aviation weather). This paper introduces the FACETs vision, the motivation for its creation, the research and development under way to explore that vision, its relevance to operational forecasting and society, and possible strategies for implementation.
Detection of False-Negative Pap Smears using the Papnet System
Authors: Troni Grazia Maria , Cipparrone Ida , Cariaggi Maria Paola , Ciatto Stefano , Miccinesi Guido , Zappa Marco , Confortini Massimo 
Published: April 2018

Aims and background False-negative cytological diagnoses represent the critical point of a screening program for early detection of cervical cancer. Computer-assisted reading using neural network technology has been suggested as a possible approach to manage the problem. The study assessed the performance and the cost-outcome ratio of computer-assisted versus conventional manual Pap smear reading. Methods One thousand routine smears, seeded with 81 false-negative smears, were independently interpreted by two readers by conventional and PAPNET-assisted reading. Results of both readings were compared in terms of: a)sensitivity for false-negative smears, b)specificity, and c) cost-outcome (cost per CIN2+ lesion detected). Results PAPNET-assisted reading showed a small increase in sensitivity only for one reader. Including the cost of PAPNET, the cost per detected lesion would be $7,543 and the cost per additional detected lesion would be $25,748. Conclusions The present study provides further evidence that PAPNET-assisted screening may allow the detection of a few extra cases of CIN2+ lesions with respect to conventional reading, though at a very high cost.
Incidence and Survival Cancer Trends in Children and Adolescents in the Provinces of Florence and Prato (Central Italy), 1985–1997
Authors: Crocetti Emanuele , Bernini Gabriella , Tamburini Angela , Miccinesi Guido , Paci Eugenio 
Published: April 2018

Aims and background The incidence of childhood and adolescent cancers has been increasing during the last decades in most Western countries. Improvements in cancer survival rates have also been observed according to the availability of more efficient therapies. Methods and study design A total of 518 cancer cases (age, 0–19 years) incident in the period 1985–1997 in the Tuscany Cancer Registry area, corresponding to the Provinces of Florence and Prato (Central Italy), were analyzed. Incidence rates and estimated annual percentage change were computed according to sex, 5-year age groups and diagnostic groups of the International Classification for Childhood Cancer. All patients were actively followed at 31.12.1998, and 5-year survival rates were computed for cases diagnosed in 1985–1990 and 1991–1997. Results Overall age-standardized incidence rates were 186.7/106 for males and 175.4 for females. In 1991–1997, standardized incident rates were 50.8 for leukemias, 44.6 for lymphomas, and 34.3 for CNS tumors. There was a marked increasing trend for lymphomas that grew at a yearly rate of +12.1% and less evident increasing tendency for leukemias, CNS tumors and carcinomas. The overall survival rate was 88% at one year, 78% at 3 years, and 74% at 5 years. A slight improving tendency in survival was evident over time. Conclusions The study pointed out that in the examined area, during 1985–1997, there was a significant increasing incidence trend for lymphomas. Survival rates were as high as in other Western countries – evidence of the high level of diagnostic and treatment services in the area.
Preliminary Study on Radioimmunodiagnosis of Experimental Tumor Models Using Technetium-99m-Labeled Anti-C-erbB-2 Monoclonal Antibody
Authors: Meenakshi Ananthanarayanan , Kumar Rayala Suresh , Ganesh Venkatraman , Kumar Nallathambi Siva 
Published: April 2018

Aims and background One of the great challenges of oncology is to improve methods for early tumor detection. Diagnosis of premalignant lesions and early stage primary tumors is crucial for the success of cancer therapy and increased survival rates. Growth factor receptors localized to the cell membrane play a vital role in cancer. Monoclonal antibodies labeled with radioisotopes have been used extensively for radioimmunodiagnosis and radioimmunotherapy of various malignancies. A preliminary study on immunoscintigraphy was carried out on animal tumor models using 99mTc-labeled monoclonal antibody CIBCgp185 generated against the C-erbB-2 oncoprotein with a view to develop technologies for in vivo radioimmunodetection and localization of human breast cancer. Methods Mammary tumor xenografts induced using BT474 cells, a breast carcinoma cell line showing overexpression of C-erbB-2, were used for immunoscintigraphic studies. Results Scintigrams showed high radiolabel uptake by the tumor tissue of the mice belonging to the experimental group, whereas in control animals no radiolabel uptake was visualized. Biodistribution studies correlated well with scintiscans. Conclusions The results indicate the potential application of this monoclonal antibody for in vivo diagnosis of occult malignancies of tumors with overexpression of C-erbB-2.
Single-Agent Irinotecan as Second-Line Weekly Chemotherapy in Elderly Patients with Advanced Colorectal Cancer
Authors: Rosati Gerardo , Cordio Stefano 
Published: April 2018

Aims and background Irinotecan is a standard option for relapsed/refractory advanced colorectal cancer. Although in a recently reported, randomized trial it was found that a regimen of irinotecan once every 3 weeks was associated with a lower incidence of severe diarrhea than with weekly treatment with similar efficacy, there is no evidence in the literature that suggests the optimal dosing strategy for the drug, along with treatment efficacy and safety, following 5-fluorouracil/oxaliplatin-based chemotherapy in elderly patients. A phase II study has reported significantly reduced toxicity when irinotecan was administered once a week for 2 weeks, followed by a week rest. Patients and methods From January 2004 to April 2005, we analyzed, retrospectively, our data on single-agent irinotecan as a second-line chemotherapy in elderly patients (≥70 years) with advanced colorectal cancer. Twenty-three patients were evaluated. CPT-11 (80 mg/m2) was given as a 60-min intravenous infusion in repeated 21-day courses comprising weekly treatment for 2 consecutive weeks followed by a 1-week rest. Tumor measurements were obtained after every third course of therapy. Toxicity was assessed weekly using the National Cancer Institute Common Toxicity Criteria, version 2. Results The median number of treatment courses received per patient was 4 (range, 1–8). All patients were assessable for toxicity and 21 for response. The most frequently observed severe toxicities were diarrhea (grade 3, 13%) and neutropenia (grade 3, 30.4%; grade 4, 8.6%). Only 1 case of neutropenic fever occurred. Other hematological and non-hematological toxicities were mild and manageable. Objective partial responses were observed in 3 patients (13%). An additional 10 patients (43%) had stable disease as their best response. To date, 12 patients have progressed with a median time-to-progression of 4.3 months and a median survival of 8.3 months. Conclusions A weekly irinotecan administration can induce tumor control in elderly patients with advanced colorectal cancer that has progressed during or shortly after 5-fluorouracil/oxaliplatin-based chemotherapy. However, a careful monitoring of hematological toxicity and special instructions to prevent and manage diarrhea are mandatory in this setting of patients.
Temozolomide and Radiotherapy as First-Line Treatment of High-Grade Gliomas
Authors: Corsa Pietro , Parisi Salvatore , Raguso Arcangela , Troiano Michele , Perrone Antonio , Cossa Sabrina , Munafò Tindara , Piombino Michele , Spagnoletti Girolamo , Borgia Francesco 
Published: April 2018

Aims and background Temozolomide, a novel alkylating agent, has shown promising results in the treatment of patients with high-grade gliomas, when used as single agent as well as in combination with radiation therapy. Materials and methods In this report we retrospectively reviewed the clinical outcome of 128 consecutive patients with a diagnosis of high-grade gliomas referred to our Institutions from April 1994 to November 2001. The first 64 patients were treated with radiotherapy alone and the other 64 with a combination of radiotherapy and temozolomide (31 with radiotherapy and adjuvant temozolomide and 33 with radiotherapy and concomitant temozolomide followed by adjuvant temozolomide). Results Grade 3 hematological toxicity was scored in 9% of 64 patients treated with radiotherapy and temozolomide. No grade 4 hematological toxicity was reported, and the other acute side effects observed were mild or easily controlled with medications. Age, histology and administration of temozolomide were statistically significant prognostic factors associated with better 2-year overall survival. In contrast, we did not observe a significant difference in overall survival between adjuvant and concomitant/adjuvant temozolomide administration. Conclusions We report the favorable results of a schedule combining radiotherapy and temozolomide in the treatment of patients with high-grade gliomas. The literature data and above all the findings of the phase III EORTC-NCIC 26981 trial suggest that actually the schedule can be used routinely in clinical practice. Further clinical studies, using temozolomide in combination with other agents, are required.
Assistance to Parents who have Lost their Child with Cancer
Authors: Clerici Carlo Alfredo , Ferrari Andrea , Massimino Maura , Luksch Roberto , Cefalo Graziella , Terenziani Monica , Casanova Michela , Spreafico Filippo , Polastri Daniela , Meazza Cristina , Podda Marta , Fossati-Bellani Franca 
Published: April 2018

Aims and background To assess the psychological needs of parents after the death of their child from cancer. Methods The study comprises a preliminary retrospective phase to identify parents who spontaneously contacted the medical staff, followed by a prospective phase in which families were contacted by telephone and were invited to a meeting. Results The retrospective study demonstrated that more than 50% of the families spontaneously sought contact with the department. In the prospective study, 17 families were contacted and the majority of them subsequently decided to come to the department for a talk. Conclusions Our experience shows that parents have a strong need to have further contact with the team that took care of their children for months. In the process of coping with bereavement, anxiety and depression are common and not necessarily pathological, though there may be psychopathological reactions that can interfere with the parents’ quality of life.
Acute Liver Failure as the Initial Manifestation of Hepatic Infiltration by a Solid Tumor: Report of 5 Cases and Review of the Literature
Authors: Alexopoulou Alexandra , Koskinas John , Deutsch Melanie , Delladetsima Johanna , Kountouras Demetrios , Dourakis Spyros P 
Published: April 2018

Background Acute liver failure is a rare complication of metastatic liver disease with a high mortality. Recognition of malignant infiltration of the liver as the cause of acute liver failure could be a diagnostic challenge. Patients The medical files of 5 patients with acute liver failure due to metastatic liver disease collected over a 4-year period (1997–2000) in our department were reviewed. Results No patient had a past history of cancer. The interval from jaundice to encephalopathy ranged from 7 to 12 days (median, 10). Physical examination revealed hepatomegaly and deep jaundice in all patients. AST elevation ranged from 147 to 1870 IU/L (median, 716 IU/L) and ALT elevation from 74 to 556 IU/L (median, 138 IU/L). All patients died within 4–14 days (median, 7) of admission. None had papillary edema or decerebrate posture before death. Four patients had concurrent renal impairment. Liver imaging studies in 2 of the 5 patients were nondiagnostic and the malignant liver infiltration was confirmed postmortem. Liver histology in all cases showed massive tumoral infiltration of the hepatic sinusoids with diffuse replacement of hepatocytes. The primary tumors were colon, gastric, small cell lung, pancreas and cancer of unknown origin. Conclusions Malignant infiltration of the liver should be taken into account in the differential diagnosis of rapidly progressive liver failure. Although effective chemotherapy has improved the survival of patients with metastatic liver disease, there has been no change in the course and outcome of acute liver failure due to malignant infiltration of the liver over the last 2 decades. A proper diagnosis by liver biopsy is mandatory to prevent such patients from being considered for liver transplant.