bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soluble GPVI is elevated in injured patients: shedding is mediated by fibrin activation of GPVI
Authors: Montague Samantha J. , Delierneux Céline , Lecut Christelle , Layios Nathalie , Dinsdale Robert J. , Lee Christine S.-M. , Poulter Natalie S. , Andrews Robert K. , Hampson Peter , Wearn Christopher M. , Maes Nathalie , Bishop Jonathan , Bamford Amy , Gardiner Chris , Lee Woei Ming , Iqbal Tariq , Moiemen Naiem , Watson Steve P. , Oury Cécile , Harrison Paul , Gardiner Elizabeth E. 
Published: February 2018

Key Points
Soluble GPVI is elevated in patients with thermal injury with sepsis, and sGPVI levels augment severity score prediction of mortality. The GPVI ligand, fibrin, induces GPVI shedding without requirement for platelet activation or signaling
The immunoglobulin heavy chain 3′ regulatory region superenhancer controls mouse B1 B-cell fate and late VDJ repertoire diversity
Authors: Ghazzaui Nour , Issaoui Hussein , Saintamand Alexis , Oblet Christelle , Carrion Claire , Denizot Yves 
Published: February 2018

Key Points
Similar to B2 B cells, the IgH 3′RR superenhancer controls μ-chain transcription and cell fate in B1 B cells. In contrast to B2 B cells, deletion of the IgH 3′RR superenhancer affects B1 B-cell late repertoire diversity.
Multiple-therapy-resistant major depressive disorder: a clinically important concept
Authors: McAllister-Williams R. H. , Christmas D. M. B. , Cleare A. J. , Currie A. , Gledhill J. , Insole L. , Malizia A. L. , McGeever M. , Morriss R. , Robinson L. J. , Scott M. , Stokes P. R. A. , Talbot P. S. , Young A. H. 
Published: February 2018

SummaryMany novel therapeutic options for depression exist that are either not mentioned in clinical guidelines or recommended only for use in highly specialist services. The challenge faced by clinicians is when it might be appropriate to consider such ‘non-standard’ interventions. This analysis proposes a framework to aid this decision.Declaration of interestIn the past 3 years R.H.M.W. has received support for research, expenses to attend conferences and fees for lecturing and consultancy work (including attending advisory boards) from various pharmaceutical companies including Astra Zeneca, Cyberonics, Eli Lilly, Janssen, LivaNova, Lundbeck, MyTomorrows, Otsuka, Pfizer, Roche, Servier, SPIMACO and Sunovion. D.M.B.C. has received fees from LivaNova for attending an advisory board. In the past 3 years A.J.C. has received fees for lecturing from Astra Zeneca and Lundbeck; fees for consulting from LivaNova, Janssen and Allergan; and research grant support from Lundbeck.In the past 3 years A.C. has received fees for lecturing from pharmaceutical companies namely Lundbeck and Sunovion. In the past 3 years A.L.M. has received support for attending seminars and fees for consultancy work (including advisory board) from Medtronic Inc and LivaNova. R.M. holds joint research grants with a number of digital companies that investigate devices for depression including Alpha-stim, Big White Wall, P1vital, Intel, Johnson and Johnson and Lundbeck through his mindTech and CLAHRC EM roles. M.S. is an associate at Blueriver Consulting providing intelligence to NHS organisations, pharmaceutical and devices companies. He has received honoraria for presentations and advisory boards with Lundbeck, Eli Lilly, URGO, AstraZeneca, Phillips and Sanofi and holds shares in Johnson and Johnson. In the past 3 years P.R.A.S. has received support for research, expenses to attend conferences and fees for lecturing and consultancy work (including attending an advisory board) from life sciences companies including Corcept Therapeutics, Indivior and LivaNova. In the past 3 years P.S.T. has received consultancy fees as an advisory board member from the following companies: Galen Limited, Sunovion Pharmaceuticals Europe Ltd, myTomorrows and LivaNova. A.H.Y. has undertaken paid lectures and advisory boards for all major pharmaceutical companies with drugs used in affective and related disorders and LivaNova. He has received funding for investigator initiated studies from AstraZeneca, Eli Lilly, Lundbeck and Wyeth.
Safety and Clinical Activity of Pembrolizumab and Multisite Stereotactic Body Radiotherapy in Patients With Advanced Solid Tumors
Authors: Luke Jason J. , Lemons Jeffrey M. , Karrison Theodore G. , Pitroda Sean P. , Melotek James M. , Zha Yuanyuan , Al-Hallaq Hania A. , Arina Ainhoa , Khodarev Nikolai N. , Janisch Linda , Chang Paul , Patel Jyoti D. , Fleming Gini F. , Moroney John , Sharma Manish R. , White Julia R. , Ratain Mark J. , Gajewski Thomas F. , Weichselbaum Ralph R. , Chmura Steven J. 
Published: February 2018

Purpose Stereotactic body radiotherapy (SBRT) may stimulate innate and adaptive immunity to augment immunotherapy response. Multisite SBRT is an emerging paradigm for treating metastatic disease. Anti-PD-1–treatment outcomes may be improved with lower disease burden. In this context, we conducted a phase I study to evaluate the safety of pembrolizumab with multisite SBRT in patients with metastatic solid tumors. Patients and Methods Patients progressing on standard treatment received SBRT to two to four metastases. Not all metastases were targeted, and metastases > 65 mL were partially irradiated. SBRT dosing varied by site and ranged from 30 to 50 Gy in three to five fractions with predefined dose de-escalation if excess dose-limiting toxicities were observed. Pembrolizumab was initiated within 7 days after completion of SBRT. Pre- and post-SBRT biopsy specimens were analyzed in a subset of patients to quantify interferon-γ–induced gene expression. Results A total of 79 patients were enrolled; three patients did not receive any treatment and three patients only received SBRT. Patients included in the analysis were treated with SBRT and at least one cycle of pembrolizumab. Most (94.5%) of patients received SBRT to two metastases. Median follow-up for toxicity was 5.5 months (interquartile range, 3.3 to 8.1 months). Six patients experienced dose-limiting toxicities with no radiation dose reductions. In the 68 patients with imaging follow-up, the overall objective response rate was 13.2%. Median overall survival was 9.6 months (95% CI, 6.5 months to undetermined) and median progression-free survival was 3.1 months (95% CI, 2.9 to 3.4 months). Expression of interferon-γ–associated genes from post–SBRT tumor biopsy specimens significantly correlated with nonirradiated tumor response. Conclusion Multisite SBRT followed by pembrolizumab was well tolerated with acceptable toxicity. Additional studies exploring the clinical benefit and predictive biomarkers of combined multisite SBRT and PD-1–directed immunotherapy are warranted.
Genomic Profiling of T-Cell Neoplasms Reveals Frequent JAK1 and JAK3 Mutations With Clonal Evasion From Targeted Therapies
Authors: Greenplate Allison , Wang Kai , Tripathi Rati M. , Palma Norma , Ali Siraj M. , Stephens Phil J. , Miller Vincent A. , Shyr Yu , Guo Yan , Reddy Nishitha M. , Kozhaya Lina , Unutmaz Derya , Chen Xueyan , Irish Jonathan M. , Davé Utpal P. 
Published: February 2018

Purpose The promise of precision oncology is that identification of genomic alterations will direct the rational use of molecularly targeted therapy. This approach is particularly applicable to neoplasms that are resistant to standard cytotoxic chemotherapy, like T-cell leukemias and lymphomas. In this study, we tested the feasibility of targeted next-generation sequencing in profiles of diverse T-cell neoplasms and focused on the therapeutic utility of targeting activated JAK1 and JAK3 in an index case. Patients and Methods Using Foundation One and Foundation One Heme assays, we performed genomic profiling on 91 consecutive T-cell neoplasms for alterations in 405 genes. The samples were sequenced to high uniform coverage with an Illumina HiSeq and averaged a coverage depth of greater than 500× for DNA and more than 8M total pairs for RNA. An index case of T-cell prolymphocytic leukemia (T-PLL), which was analyzed by targeted next-generation sequencing, is presented. T-PLL cells were analyzed by RNA-seq, in vitro drug testing, mass cytometry, and phospho-flow. Results One third of the samples had genomic aberrations in the JAK-STAT pathway, most often composed of JAK1 and JAK3 gain-of-function mutations. We present an index case of a patient with T-PLL with a clonal JAK1 V658F mutation that responded to ruxolitinib therapy. After relapse developed, an expanded clone that harbored mutant JAK3 M511I and downregulation of the phosphatase, CD45, was identified. We demonstrate that the JAK missense mutations were activating, caused pathway hyperactivation, and conferred cytokine hypersensitivity. Conclusion These results underscore the utility of profiling occurrences of resistance to standard regimens and support JAK enzymes as rational therapeutic targets for T-cell leukemias and lymphomas.
Hypoxic-Ischemic Encephalopathy and Other Neonatal Encephalopathies
Authors: Glass Hannah C. 
Published: February 2018

ABSTRACTPURPOSE OF REVIEWNeonatal encephalopathy is the most common condition in neonates encountered by child neurologists. The etiology is most often global hypoxia-ischemia due to failure of cerebral perfusion to the fetus caused by uterine, placental, or umbilical cord compromise prior to or during delivery. Other etiologies of neonatal encephalopathy include ischemic stroke and intracranial hemorrhage, infection, developmental anomalies, and inborn errors of metabolism.RECENT FINDINGSTherapeutic hypothermia is standard of care for the treatment of neonatal encephalopathy presumed to be caused by hypoxia-ischemia. The number needed to treat is approximately 6 to 7 to prevent one child from either death or disability at age 18 to 22 months. EEG monitoring and MRI are important tools in determining the etiology of encephalopathy and prognosis of the infant.SUMMARYNeonatal encephalopathy is a heterogeneous disorder that is characterized by alterations in mental status, hypotonia, seizures, and abnormalities in feeding and respiration. The most common cause of neonatal encephalopathy is hypoxic-ischemic encephalopathy, for which treatment with 72 hours of therapeutic hypothermia is associated with reduced death or disability.
Nervous System Malformations
Authors: Gaitanis John , Tarui Tomo 
Published: February 2018

ABSTRACTPURPOSE OF REVIEWThis article provides an overview of the most common nervous system malformations and serves as a reference for the latest advances in diagnosis and treatment.RECENT FINDINGSMajor advances have occurred in recognizing the genetic basis of nervous system malformations. Environmental causes of nervous system malformations, such as perinatal infections including Zika virus, are also reviewed. Treatment for nervous system malformations begins prior to birth with prevention. Folic acid supplementation reduces the risk of neural tube defects and is an important part of health maintenance for pregnant women. Fetal surgery is now available for prenatal repair of myelomeningocele and has been demonstrated to improve outcomes.SUMMARYEach type of nervous system malformation is relatively uncommon, but, collectively, they constitute a large population of neurologic patients. The diagnosis of nervous system malformations begins with radiographic characterization. Genetic studies, including chromosomal microarray, targeted gene sequencing, and next-generation sequencing, are increasingly important aspects of the assessment. A genetic diagnosis may identify an associated medical condition and is necessary for family planning. Treatment consists primarily of supportive therapies for developmental delays and epilepsy, but prenatal surgery for myelomeningocele offers a glimpse of future possibilities. Prognosis depends on multiple clinical factors, including the examination findings, imaging characteristics, and genetic results. Treatment is best conducted in a multidisciplinary setting with neurology, neurosurgery, developmental pediatrics, and genetics working together as a comprehensive team.
Neurocutaneous Disorders
Authors: Rosser Tena 
Published: February 2018

ABSTRACTPURPOSE OF REVIEWThis article presents an up-to-date summary of the genetic etiology, diagnostic criteria, clinical features, and current management recommendations for the most common neurocutaneous disorders encountered in clinical adult and pediatric neurology practices.RECENT FINDINGSThe phakomatoses are a phenotypically and genetically diverse group of multisystem disorders that primarily affect the skin and central nervous system. A greater understanding of the genetic and biological underpinnings of numerous neurocutaneous disorders has led to better clinical characterization, more refined diagnostic criteria, and improved treatments in neurofibromatosis type 1, Legius syndrome, neurofibromatosis type 2, Noonan syndrome with multiple lentigines, tuberous sclerosis complex, Sturge-Weber syndrome, and incontinentia pigmenti.SUMMARYNeurologists require a basic knowledge of and familiarity with a wide variety of neurocutaneous disorders because of the frequent involvement of the central and peripheral nervous systems. A simple routine skin examination can often open a broad differential diagnosis and lead to improved patient care.
Epilepsy Syndromes in Childhood
Authors: Pearl Phillip L. 
Published: February 2018

ABSTRACT

PURPOSE OF REVIEW
Epilepsy syndromes are an important clinical construct in pediatric epilepsy, as they encompass recognizable patterns seen in patients with epilepsies, whether of the more benign variety or associated with encephalopathy.

RECENT FINDINGS
Syndromes may be organized by age of onset: neonatal, infantile, childhood, or adolescent. The assignment of a syndrome has specific implications for diagnosis, management, and prognostication. The 2010 revised classification of the epilepsies by the International League Against Epilepsy preserved the syndrome approach, while progress in genetics continues to advance our understanding of the pathophysiology and overlap of the epilepsy syndromes.

SUMMARY
Given that mutations of the same gene may cause both encephalopathic and relatively benign epilepsies, an understanding of the pediatric epilepsy syndromes remains vital to patient care.
Calcium signaling mediates five types of cell morphological changes to form neural rosettes
Authors: Hříbková Hana , Grabiec Marta , Klemová Dobromila , Slaninová Iva , Sun Yuh-Man 
Published: February 2018

ABSTRACT
Neural rosette formation is a critical morphogenetic process during neural development, whereby neural stem cells are enclosed in rosette niches to equipoise proliferation and differentiation. How neural rosettes form and provide a regulatory micro-environment remains to be elucidated. We employed the human embryonic stem cell-based neural rosette system to investigate the structural development and function of neural rosettes. Our study shows that neural rosette formation consists of five types of morphological change: intercalation, constriction, polarization, elongation and lumen formation. Ca2+ signaling plays a pivotal role in the five steps by regulating the actions of the cytoskeletal complexes, actin, myosin II and tubulin during intercalation, constriction and elongation. These, in turn, control the polarizing elements, ZO-1, PARD3 and β-catenin during polarization and lumen production for neural rosette formation. We further demonstrate that the dismantlement of neural rosettes, mediated by the destruction of cytoskeletal elements, promotes neurogenesis and astrogenesis prematurely, indicating that an intact rosette structure is essential for orderly neural development.
Changes in Cycling and Incidence of Overweight and Obesity among Danish Men and Women
Authors: RASMUSSEN MARTIN GILLIES , OVERVAD KIM , TJØNNELAND ANNE , JENSEN MAJKEN K. , ØSTERGAARD LARS , GRØNTVED ANDERS 
Published: February 2018

ABSTRACTPurposeOverweight and obesity are associated with increased risk of several noncommunicable diseases and are a growing public health issue. The primary purpose of the current study was to investigate incidence of overweight and obesity according to 5-yr cycling habits. The secondary purpose was to investigate incidence of remission from overweight and obesity according to 5-yr cycling habits.MethodsWe analyzed 9014 men and 8661 women without chronic disease who between 1993 and 2003 completed two assessments approximately 5 yr apart. At both assessments, participants reported habitual cycling habits. Also, body weight and waist circumference were measured by a laboratory technician at baseline and self-assessed at second examination. We computed multivariable adjusted odds ratios (OR) with 95% confidence intervals (CI) for development of and remission from abdominal and general overweight and obesity, according to 5-yr cycling habits.ResultsContinued cycling was associated with lower odds for incidence of abdominal (men, >102 cm; women, >88 cm) and incidence of general (body mass index ≥30 kg·m−2) obesity; compared with no cycling, OR (95% CI) values were 0.82 (0.74–0.91) and 0.74 (0.60–0.92) for abdominal and general obesity, respectively. Also, those who initiated cycling had lower odds for incidence of abdominal obesity; OR (95% CI) was 0.85 (0.73–1.00) relative to no cycling. Although we found no evidence of remission from abdominal and general overweight and obesity according to 5-yr cycling habits, those who continued cycling had significantly larger decreases in waist circumference relative to noncyclists (β coefficient (95% CI), −0.95 cm (−1.56 to −0.33 cm)).ConclusionsContinued cycling compared with no cycling was associated with lower odds for abdominal and general obesity. Also, late-in-life initiation of cycling was associated with lower odds for abdominal obesity relative to no cycling.
Typification and reestablishment of the Linnaean name Dalechampiacolorata (Euphorbiaceae)
Authors: Pereira-Silva Rafaela Alves , Athiê-Souza Sarah Maria , Armbruster W. Scott , de Melo André Laurênio , de Salesi Margareth Ferreira 
Published: February 2018

AbstractRevisionary studies of Dalechampia sect. Dalechampia have revealed the need to lectotypify D. colorata and that it represents a distinct species rather than a synonym of D. tiliifolia. Dalechampia karsteniana is interpreted to be a synonym of D. colorata.
Phylogeny of the Inula group (Asteraceae: Inuleae): Evidence from nuclear and plastid genomes and a recircumscription of Pentanema
Authors: Gutiérrez-Larruscain David , Santos-Vicente María , Anderberg Arne A. , Rico Enrique , Martínez-Ortega María Montserrat 
Published: February 2018

AbstractThe Inula complex (Asteraceae: Inulinae) is a monophyletic group which comprises eight genera distributed in Eurasia and Africa: Amblyocarpum, Carpesium, Chrysophthalmum, Inula, Pentanema, Rhanteriopsis, Telekia, and Varthemia. With the aim to shed light on the circumscription of these genera, phylogenetic analyses were performed with 293 new DNA sequences (ITS region from nrDNA and three plastid spacers from cpDNA: rps16–trnQ, rpl32–trnL, ndhF–rpl32). It is concluded that both Inula and Pentanema are paraphyletic and that generic delimitations within the Inula complex need to be revised. Based on the results of the analyses, together with morphological and karyological data, we argue that the best solution is a new circumscription of the genus Pentanema including an amended description and 24 new combinations of former Inula species. Resurrection of the names Codonocephalum, Monactinocephalus and Vicoa is proposed to preserve the monophyly of the genera included in the Inula complex. Incongruences between nrDNA and cpDNA are documented and discussed.
Asset Pricing with Disagreement and Uncertainty About the Length of Business Cycles
Authors: Andrei Daniel , Carlin Bruce , Hasler Michael 
Published: February 2018

We study an economy with incomplete information in which two agents are uncertain and disagree about the length of business cycles. That is, the agents do not question whether the economy is growing or not, but instead continuously estimate how long economic cycles will last—i.e., they learn about the persistence of fundamentals. Learning about persistence generates high and persistent stock return volatility mostly during recessions, but also (to a smaller extent) during economic booms. Disagreement among agents fluctuates and earns a risk premium. A clear risk–return trade-off appears only when conditioning on the sign and magnitude of disagreement. We confirm these predictions empirically.This paper was accepted by Neng Wang, finance.
First-Place Loving and Last-Place Loathing: How Rank in the Distribution of Performance Affects Effort Provision
Authors: Gill David , Kissová Zdenka , Lee Jaesun , Prowse Victoria 
Published: February 2018

Rank-order relative-performance evaluation, in which pay, promotion, symbolic awards, and educational achievement depend on the rank of individuals in the distribution of performance, is ubiquitous. Whenever organizations use rank-order relative-performance evaluation, people receive feedback about their rank. Using a real-effort experiment, we aim to discover whether people respond to the specific rank that they achieve. In particular, we leverage random variation in the allocation of rank among subjects who exerted the same effort to obtain a causal estimate of the rank response function that describes how effort provision responds to the content of rank-order feedback. We find that the rank response function is U-shaped. Subjects exhibit “first-place loving” and “last-place loathing”: that is, subjects work hardest after being ranked first or last. We discuss implications of our findings for the optimal design of performance feedback policies, workplace organizational structures, and incentives schemes. Data and the supplementary web appendix are available at https://doi.org/10.1287/mnsc.2017.2907 . This paper was accepted by Uri Gneezy, behavioral economics.
College Connectedness: The Student Perspective
Authors: Farrell Laura Catherine , Jorgenson Derek , Fudge Julie , Pritchard Andrew 
Published: February 2018

Connectedness and integration are essential elements of student satisfaction, academic success, and retention. Despite its importance in the lives of college students, research on connectedness has approached the concept from definitional perspectives other than those of students. This multi-study explores connectedness from the student perspective while drawing from social identity theory and student involvement theory. In Study 1, students described their experiences and perceptions of connectedness in focus groups. Study 2 built on the qualitative findings of Study 1 and empirically tested connectedness as defined by the students. Results of the study indicate the need for a student definition of connectedness and provide practical suggestions for those in higher education.Keywords: connectedness, social identity theory, student involvement theory, instrument design, higher education
The Effects of different nitrogen doses on antioxidant and antimicrobial activity of Stevia (Stevia rebaudiana Bert.)
Authors: Atas Mehmet , Eruygur Nuraniye , Ucar Esra , Ozyigit Yasar , Turgut Kenan 
Published: February 2018

In this study, the efficiency of the different nitrogen doses (0, 5, 10, 15 and 20 kg ha-1) on biological activity levels (antioxidant and antimicrobial activity) of Stevia rebaudiana Bert. was investigated. In addition, methanol extracts were obtained by maceration method from different doses of fertilizer applied stevia. The components in methanol extracts of plants were determined by gas chromatography-mass spectrometry (GC-MS) method. Antimicrobial activities of stevia extracts were investigated by microdilution method. The antioxidant activity evaluated by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, ferric thiocyanate (FTC), thiobarbituric acid (TBA), reducing power, total phenol content (TPC), and total flavonoid content (TFC) methods. According to the results, the fertilizer doses effects on antimicrobial activity of stevia were not made much difference. But in antioxidant activity, there were some variations in the activity-dependent on fertilizer amount.