bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kanagawa Investigation of the Total Check-up Data from the National database (KITCHEN): protocol for data-driven population-based repeated cross-sectional and 6-year cohort studies
Authors: Nakajima Kei , Iwane Taizo , Higuchi Ryoko , Shibata Michi , Takada Kento , Uda Jun , Anan Mami , Sugiyama Michiko , Nakamura Teiji 
Published: February 2019

IntroductionThe unmitigated incidence of cardiometabolic diseases, such as type 2 diabetes and metabolic syndrome, has gained attention in Japan. ‘Big data’ can be useful to clarify conflicting observations obtained from studies with small samples and about rare conditions that are often neglected. We epidemiologically address these issues using data from health check-ups conducted in Kanagawa Prefecture, the prefecture with the second largest population in Japan, in the Kanagawa Investigation of the Total Check-up Data from the National Database (KITCHEN).Methods and analysisThis research consists of a series of population-based cross-sectional studies repeated from 2008–2014 and 6-year cohort studies. Since 2017, we have reviewed the data of people living in Kanagawa Prefecture who underwent a health check-up mainly for general health and the prevention of metabolic syndrome. The sample size ranges from 1.2 million to 1.8 million people in the cross-sectional studies and from 370 000 to 590 000 people in the cohort studies. These are people aged 40–74 years, whose clinical parameters were measured and who responded individually to a questionnaire. We investigate potential associations and causalities of various aetiologies, including diabetes and metabolic syndrome, using clinical data and lifestyle information. With multidisciplinary analysis, including data-driven analysis, we expect to obtain a wide range of novel findings, to confirm indeterminate previous findings, especially in terms of cardiometabolic disease, and to provide new perspectives for human health promotion and disease prevention.Ethics and disseminationEthical approval was received from the Ethics Committee of Kanagawa University of Human Services (10-43). The protocol was approved in December 2016 by the Japanese Ministry of Health, Labour and Welfare (No. 121). The study results will be disseminated through open platforms including journal articles, relevant conferences and seminar presentations.
Can we IMPROVE cardiovascular outcomes through phosphate lowering in CKD? Rationale and protocol for the IMpact of Phosphate Reduction On Vascular End-points in Chronic Kidney Disease (IMPROVE-CKD) study
Authors: Lioufas Nicole , Toussaint Nigel D , Pedagogos Eugenia , Elder Grahame , Badve Sunil V , Pascoe Elaine , Valks Andrea , Hawley Carmel 
Published: February 2019

IntroductionPatients with chronic kidney disease (CKD) are at heightened cardiovascular risk, which has been associated with abnormalities of bone and mineral metabolism. A deeper understanding of these abnormalities should facilitate improved treatment strategies and patient-level outcomes, but at present there are few large, randomised controlled clinical trials to guide management. Positive associations between serum phosphate and fibroblast growth factor 23 (FGF-23) and cardiovascular morbidity and mortality in both the general and CKD populations have resulted in clinical guidelines suggesting that serum phosphate be targeted towards the normal range, although few randomised and placebo-controlled studies have addressed clinical outcomes using interventions to improve phosphate control. Early preventive measures to reduce the development and progression of vascular calcification, left ventricular hypertrophy and arterial stiffness are crucial in patients with CKD.Methods and analysisWe outline the rationale and protocol for an international, multicentre, randomised parallel-group trial assessing the impact of the non-calcium-based phosphate binder, lanthanum carbonate, compared with placebo on surrogate markers of cardiovascular disease in a predialysis CKD population—theIMpact ofPhosphateReductionOnVascularEnd-points (IMPROVE)-CKD study. The primary objective of the IMPROVE-CKD study is to determine if the use of lanthanum carbonate reduces the burden of cardiovascular disease in patients with CKD stages 3b and 4 when compared with placebo. The primary end-point of the study is change in arterial compliance measured by pulse wave velocity over a 96-week period. Secondary outcomes include change in aortic calcification and biochemical parameters of serum phosphate, parathyroid hormone and FGF-23 levels.Ethics and disseminationEthical approval for the IMPROVE-CKD trial was obtained by each local Institutional Ethics Committee for all 17 participating sites in Australia, New Zealand and Malaysia prior to study commencement. Results of this clinical trial will be published in peer-reviewed journals and presented at conferences.Trial registration numberACTRN12610000650099.
Supra-inguinal injection for fascia iliaca compartment block results in more consistent spread towards the lumbar plexus than an infra-inguinal injection: a volunteer study
Authors: Vermeylen Kris , Desmet Matthias , Leunen Ine , Soetens Filiep , Neyrinck Arne , Carens Dirk , Caerts Ben , Seynaeve Patrick , Hadzic Admir , Van de Velde Marc 
Published: February 2019

Background and objectivesLumbar plexus block has been used to provide postoperative analgesia after lower limb surgery. The fascia iliaca compartment block (FICB) has been proposed as an anterior approach of the lumbar plexus targeting the femoral, obturator and lateral femoral cutaneous nerve. However, both radiological and clinical evidence demonstrated that an infra-inguinal approach to the fascia iliaca compartment does not reliably block the three target nerves.We hypothesized that a supra-inguinal approach of the fascia iliaca compartment results in a more consistent block of the three target nerves than an infra-inguinal approach.MethodsWe performed a randomized controlled, double-blind trial in 10 healthy volunteers. Both an infra-inguinal FICB (I-FICB) and a supra-inguinal FICB (S-FICB) were performed on the left or the right side in each volunteer. Forty milliliters of lidocaine 0.5% was injected with each approach. Sensory and motor block and spread of local anesthetics (LA) on MRI were assessed.ResultsAfter an S-FICB, 80% of the volunteers had a complete sensory block of the medial, anterior and lateral region of the thigh, compared with 30% after an I-FICB (p=0.035). There was an insignificant effect on motor function with both approaches. After an S-FICB, in 8 out of 10 volunteers there was spread of LA in the expected anatomic location of the obturator nerve on MRI compared with 1 out of 10 volunteers after an I-FICB (p=0.0017). The cranial spread of LA after an S-FICB on MRI was higher than after an I-FICB (p=0.007), whereas there was a more caudal spread of LA on MRI after an I-FICB than after an S-FICB (p=0.005).ConclusionsAn S-FICB produces a more complete sensory block of the medial, anterior and lateral region of the thigh, compared with an I-FICB. Our study demonstrates that an S-FICB with 40 mL of LA more reliably spreads LA to the anatomical location of the three target nerves of the lumbar plexus on MRI than an I-FICB. An S-FICB also leads to a more consistent spread in a cranial direction under the fascia iliaca and around the psoas muscle.Clinical trial registrationThis work was registered with the European clinical trial registry: Identifier Eudra CT 2015-004607-24.
Predicting program properties from 'big code'
Authors: Raychev Veselin , Vechev Martin , Krause Andreas 
Published: February 2019

We present a new approach for predicting program properties from large codebases (aka "Big Code"). Our approach learns a probabilistic model from "Big Code" and uses this model to predict properties of new, unseen programs.

The key idea of our work is to transform the program into a representation that allows us to formulate the problem of inferring program properties as structured prediction in machine learning. This enables us to leverage powerful probabilistic models such as Conditional Random Fields (CRFs) and perform
joint
prediction of program properties.

As an example of our approach, we built a scalable prediction engine called JSNICE for solving two kinds of tasks in the context of JavaScript: predicting (syntactic) names of identifiers and predicting (semantic) type annotations of variables. Experimentally, JSNICE predicts correct names for 63% of name identifiers and its type annotation predictions are correct in 81% of cases. Since its public release at http://jsnice.org, JSNice has become a popular system with hundreds of thousands of uses.
By formulating the problem of inferring program properties as structured prediction, our work opens up the possibility for a range of new "Big Code" applications such as de-obfuscators, decompilers, invariant generators, and others.
Spatiotemporal Regulation of Tumor Angiogenesis by Circulating Chromogranin A Cleavage and Neuropilin-1 Engagement
Authors: Dallatomasina Alice , Gasparri Anna Maria , Colombo Barbara , Sacchi Angelina , Bianco Mimma , Daniele Tiziana , Esposito Antonio , Pastorino Fabio , Ponzoni Mirco , Marcucci Fabrizio , Curnis Flavio , Corti Angelo 
Published: February 2019

Abstract

The unbalanced production of pro- and antiangiogenic factors in tumors can lead to aberrant vasculature morphology, angiogenesis, and disease progression. In this study, we report that disease progression in various murine models of solid tumors is associated with increased cleavage of full-length chromogranin A (CgA), a circulating vasoregulatory neurosecretory protein. Cleavage of CgA led to the exposure of the highly conserved PGPQLR site, which corresponds to residues 368–373 of human CgA1-373, a fragment that has proangiogenic activity. Antibodies against this site, unable to bind full-length CgA, inhibited angiogenesis and reduced tumor perfusion and growth. The PGPQLR sequence of the fragment, but not of the precursor, bound the VEGF-binding site of neuropilin-1; the C-terminal arginine (R373) of the sequence was crucial for binding. The proangiogenic activity of the CgA1-373 was blocked by anti-neuropilin-1 antibodies as well as by nicotinic acetylcholine receptor antagonists, suggesting that these receptors, in addition to neuropilin-1, play a role in the proangiogenic activity of CgA1-373. The R373 residue was enzymatically removed in plasma, causing loss of neuropilin-1 binding and gain of antiangiogenic activity. These results suggest that cleavage of the R373R374 site of circulating human CgA in tumors and the subsequent removal of R373 in the blood represent an important “on/off” switch for the spatiotemporal regulation of tumor angiogenesis and may serve as a novel therapeutic target.

Significance:
This work reveals that the interaction between fragmented chromogranin A and neuropilin-1 is required for tumor growth and represents a novel potential therapeutic target.
LINC00261 Is an Epigenetically Regulated Tumor Suppressor Essential for Activation of the DNA Damage Response
Authors: Shahabi Shandy , Kumaran Vishaly , Castillo Jonathan , Cong Zhengmin , Nandagopal Gopika , Mullen Daniel J. , Alvarado Alexander , Correa Michele Ramos , Saizan Autumn , Goel Riya , Bhat Amrita , Lynch Sean K. , Zhou Beiyun , Borok Zea , Marconett Crystal N. 
Published: February 2019

Abstract

Lung cancer is the leading cause of cancer-related death in the United States. Long noncoding RNAs (lncRNA) are a class of regulatory molecules whose role in lung carcinogenesis is poorly understood. In this study, we profiled lncRNA expression in lung adenocarcinoma (LUAD) cell lines, compared their expression with that of purified alveolar epithelial type II cells (the purported cell of origin for LUAD), cross-referenced these with lncRNAs altered in the primary human tumors, and interrogated for lncRNAs whose expression correlated with patient survival. We identified LINC00261, a lncRNA with unknown function in LUAD, adjacent to the pioneering transcription factor FOXA2. Loss of LINC00261 was observed in multiple tumor types, including liver, breast, and gastric cancer. Reintroduction of LINC00261 into human LUAD cell lines inhibited cell migration and slowed proliferation by inducing G2–M cell-cycle arrest, while upregulating DNA damage pathway genes and inducing phosphorylation-mediated activation of components of the DNA damage pathway. FOXA2 was able to induce LINC00261 expression, and the entire locus underwent hypermethylation in LUAD, leading to loss of expression. We have thus identified an epigenetically deregulated lncRNA, whose loss of expression in LUAD promotes the malignant phenotype and blocks activation of the DNA damage machinery, predisposing lung cells to cancer development.

Significance:
These findings identify LINC00261 as a tumor suppressor that blocks cellular proliferation by activating the DNA damage response and suggest that epigenetic therapy to inhibit DNA methylation may enhance treatment of LUAD.
Assassination and Judicial Misconduct in Cold War Greece: The Polk/Staktopoulos Case in Retrospect
Authors: Iatrides John O. 
Published: February 2019

Abstract
In May 1948, as the Cold War escalated and the Communist insurgency in Greece intensified, the assassination of CBS News journalist George Polk in Salonica became an international cause célèbre. Polk had openly criticized the Greek government and questioned the U.S. government's support of an undemocratic regime. Most probably, he was killed trying to reach an insurgent command post to interview guerrilla leaders about the civil war. With no claims of responsibility for the murder and no credible forensic evidence, suspicions of culpability fell on many actors, including the Communists, extreme rightwing elements, common criminals, and rogue British intelligence operatives. Although responsibility for identifying and bringing to justice the guilty fell squarely on the Greek authorities, the country's heavy dependence on U.S. assistance enabled U.S. officials and journalists to influence the case. Eager to blame the crime on the Communists and produce quick results, Greek police and justice officials fabricated a case against two known Communists (never apprehended) and a small-time reporter, Gregory Staktopoulos, whose incoherent confessions were clearly coerced. Staktopoulos's trial, conviction, long imprisonment, and failed appeals to the country's highest court left an indelible stigma on Greek justice. Polk's murder—which has never been solved—and Staktopoulos's cruel fate illustrate the powerfully corrosive impact of Cold War perceptions and priorities on the institutions of Western democracies.
Shattered Hopes amid Violent Repression: The 1956 Hungarian Revolution and the United Nations (Part 2)
Authors: Nagy András 
Published: February 2019

Abstract
Few historical events over the past 70 years have rivaled the 1956 Hungarian revolution in its domestic and international impact. The research presented in the first part of this article (published in the Fall 2017 issue of the journal), which was based largely on recently declassified archival documents, focused on a specific aspect of the international response to the revolution—namely, the efforts of the United Nations (UN) to deal with urgent events during and immediately after the revolution. This second part focuses on the tragic consequences of the revolution, including trials, imprisonments, and executions, in the years that followed. The limitations of the UN in this instance have rarely been discussed, particularly by the organization's supporters. The silence surrounding these issues has affected dissidents and others throughout the world confronting dictatorial regimes. An understanding of what went wrong is crucial if the UN is to be more effective in the future.
Influence of Tropical SSTs on the Interannual Variation of the Summer Monsoon Break over the Western North Pacific
Authors: Xu Ke , Lu Riyu , Kim Baek-Jo , Mao Jiangyu , Park Jong-Kil 
Published: February 2019

AbstractThe break of the western North Pacific (WNP) summer monsoon (WNPSM) occurs climatologically in early August and is accompanied by a remarkable suppression of convection over the ocean east of the Mariana Islands (10°–20°N, 140°–160°E). This suppression of convection is sandwiched between two convection peaks in late July and mid-August. Two types of monsoon break are identified in the interannual variation of the WNPSM break in the period 1979–2015, exhibiting a distinct subseasonal evolution of convection that is either in phase or out of phase with the climatological evolution. The preceding SST anomalies in the tropical WNP during early and mid-July are responsible for the interannual variation of the monsoon break. Warm (cold) SST anomalies induce an advanced (delayed) evolution of the WNPSM, with the establishment of strong convection in late July (early August) followed by a monsoon break in early August (mid-August). The subseasonal evolution of convection is therefore in phase (out of phase) with that of the climatological mean. The above SST anomalies mainly result from the local wind–evaporation–SST positive feedback during spring and summer. This local air–sea interaction is still robust after the linear regression components related to the variability of ENSO are excluded from the original fields, indicating that it is, to a large extent, independent of ENSO. The ENSO decaying phases have a secondary role in modulating the SST anomalies related to the WNPSM break.
A stemness screen reveals C3orf54/INKA1 as a promoter of human leukemia stem cell latency
Authors: Kaufmann Kerstin B. , Garcia-Prat Laura , Liu Qiang , Ng Stanley W. K. , Takayanagi Shin-Ichiro , Mitchell Amanda , Wienholds Erno , van Galen Peter , Cumbaa Christian A. , Tsay Mike J. , Pastrello Chiara , Wagenblast Elvin , Krivdova Gabriela , Minden Mark D. , Lechman Eric R. , Zandi Sasan , Jurisica Igor , Wang Jean C. Y. , Xie Stephanie Z. , Dick John E. 
Published: February 2019

AbstractThere is a growing body of evidence that the molecular properties of leukemia stem cells (LSCs) are associated with clinical outcomes in acute myeloid leukemia (AML), and LSCs have been linked to therapy failure and relapse. Thus, a better understanding of the molecular mechanisms that contribute to the persistence and regenerative potential of LSCs is expected to result in the development of more effective therapies. We therefore interrogated functionally validated data sets of LSC-specific genes together with their known protein interactors and selected 64 candidates for a competitive in vivo gain-of-function screen to identify genes that enhanced stemness in human cord blood hematopoietic stem and progenitor cells. A consistent effect observed for the top hits was the ability to restrain early repopulation kinetics while preserving regenerative potential. Overexpression (OE) of the most promising candidate, the orphan gene C3orf54/INKA1, in a patient-derived AML model (8227) promoted the retention of LSCs in a primitive state manifested by relative expansion of CD34+ cells, accumulation of cells in G0, and reduced output of differentiated progeny. Despite delayed early repopulation, at later times, INKA1-OE resulted in the expansion of self-renewing LSCs. In contrast, INKA1 silencing in primary AML reduced regenerative potential. Mechanistically, our multidimensional confocal analysis found that INKA1 regulates G0 exit by interfering with nuclear localization of its target PAK4, with concomitant reduction of global H4K16ac levels. These data identify INKA1 as a novel regulator of LSC latency and reveal a link between the regulation of stem cell kinetics and pool size during regeneration.
Taking a “BiTE out of ALL”: blinatumomab approval for MRD-positive ALL
Authors: Curran Emily , Stock Wendy 
Published: February 2019

Abstract
Blinatumomab, a bispecific T-cell engager (BiTE) associated with improved survival in relapsed or refractory acute lymphoblastic leukemia (ALL), was recently approved for treatment of minimal residual disease (MRD). MRD is an important predictor of survival in ALL, and recent studies suggest that achievement of MRD-negativity with blinatumomab improves outcomes in patients with ALL. However, further research is needed to determine how to optimally incorporate blinatumomab, and other novel therapies, into current therapies for ALL.
Pengambilan keputusan investasi Investor di pasar modal indonesia ditinjau dari Teori reasoned action
Authors: Listyarti Indra 
Published: February 2019

Penelitian ini bertujuan untuk mengkaji factor-faktor yang mempengaruhi perilaku investor ketika melakukan keputusan investasi ditinjau dari Teori Reasoned Action. Penelitian melibatkan 190 investor di pasar modal Indonesia dan analisis dilakukan dengan regresi linier berganda. Uji hipotesis dengan t-test untuk menguji pengaruh variabel independen secara parsial terhadap variabel dependen. Hasilnya menunjukkan bahwa Faktor Makro berpengaruh positif signifikan terhadap informasi teknikal. Informasi keuangan, faktor makro dan norma subyektif berpengaruh positif dan signifikan terhadap niat investor. Niat investor dan informasi keuangan berpengaruh positif signifikan terhadap keputusan investasi. Lebih jauh hasil penelitian ini menjelaskan bahwa informasi keuangan memegang kontribusi besar dalam membentuk niat investor dan keputusan investasi.
Pengekang Crossties di Zona Tekan Balok dengan Pembebanan Siklik
Authors: Priastiwi Yulita Arni , Imran Iswandi , Nuroji Nuroji , Hidayat Arif 
Published: February 2019

Crossties that was installed as a confinement in the compression zone of the beam is proven can increase the ductility, especially when receiving the earthquake load. Using an experimental study, this paper explains the effect of crossties which was installed in compression zone of the beam. The model was a simplification of the plastic hinge of the beam. The beam was enlarged in the center of the span and would be loaded with a cyclic of point load, so as to produced the largest moment and shear fields in the face beam of the column. Moreover, the loading was provided by the displacement control system to achieve the ultimate condition. The results show that the crossties significantly increases the displacement and curvature ductility of the beams of 58.7% and 78.2%, respectively, compared to the beam without confinement. In addition, the load cycle formed by cyclic loading increases to 43 cycles in beam with crossties, meanwhile the beam without confinement can only survive up to 33 cycles. The crossties could also increase the cumulative value of inelastic displacement that occurs up to 98%, whereas its energy dissipation value is six times than the beam without confinement. On the other hand, the maximum load and capacity moment only increase about 6.5%.
First record of Caulerpa prolifera in the Azores (NE Atlantic)
Authors: Cacabelos Eva , Faria João , Martins Gustavo M. , Mir Carles , Parente Manuela Isabel , Gabriel Daniela , Sánchez Rocío , Altamirano María , Costa Ana Cristina , Prud’homme van Reine Willem , Neto Ana Isabel 
Published: February 2019

Abstract
This paper reports a recently discovered population of Caulerpa prolifera in the Azores (NE Atlantic), which becomes the westernmost record of this species in European waters. Morphological, anatomical and molecular characters were investigated for species recognition. The occurrence of the species in the Azores represents a northern expansion of its distributional range, covering now the whole Macaronesia region. It may have been brought by rafting from the western Atlantic through the Gulf Stream, but human-assisted transport may also have been involved in its arrival or dispersion.