bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surgically treated lung cancer patients: do they all smoke and would they all have been detected with lung cancer screening?
Authors: Laisaar Tanel , Sarana Bruno , Benno Indrek , Laisaar Kaja-Triin 
Published: August 2018

Since publication of the National Lung Cancer Screening Trial (NLST) results early lung cancer detection has been widely studied, targeting individuals based on smoking history and age. However, over recent decades several changes in lung cancer epidemiology, including risk factors, have taken place. The aim of the current study was to explore smoking prevalence among lung cancer patients who had been treated surgically or undergone a diagnostic operation and whether these patients would have met the NLST inclusion criteria.All patients operated on for lung cancer in a university hospital in Estonia between 2009 and 2015 were included. Data were collected from hospital records.426 patients were operated on for lung cancer, with smoking history properly documented in 327 patients (87 females; median age 67 years). 170 (52%) patients were smokers, 97 (30%) patients were ex-smokers and 60 (18%) patients were nonsmokers. The proportion of females among smokers was 15%, among ex-smokers was 9% and among nonsmokers was 87%. 107 of our patients would not have met the NLST age criteria and 128 of our patients would not have met the NLST smoking criteria. In total, 183 patients (56% (79% of females and 48% of males)) would not have met the NLST inclusion criteria.Only half of surgically treated lung cancer patients were current smokers and more than half did not meet the NLST inclusion criteria.
Gel electrophoresis of human sperm: a simple method for evaluating sperm protein quality
Authors: Fanny Jumeau , Julien Sigala , Francisco-Jose Fernandez-Gomez , Sabiha Eddarkaoui , Sophie Duban-Deweer , Luc Buée , Hélène Béhal , Nicolas Sergeant , Valérie Mitchell 
Published: August 2018

AbstractBackgroundThe limitations of conventional sperm analyses have highlighted the need for additional means of evaluating sperm quality.MethodsIn a study of a cohort of 245 men with known conventional sperm parameters, one-dimensional PAGE was used to monitor protein content and quality in samples from individual ejaculates.ResultsThe sperm protein content varied markedly from sample to another, especially in the high-molecular-weight range. The intensity of the 80–110 kDa bands was correlated with progressive motility (r = 0.15,p = 0.015)and was significantly higher (p = 0.0367) in the group of men with conventional parameters above the World Health Organization’s 2010 reference values than in the group with at least one subnormal parameter (i.e. semen volume, sperm concentration, sperm count per ejaculate, progressive motility, proportion of normal forms or multiple anomaly index below the lower reference value). Using mass spectrometry, the 80–110 kDa bands were found to correspond primarily to three proteins from the flagellum’s fibrous sheath: A-kinase anchor protein 4, A-kinase anchor protein 3, and spermatogenic cell-specific type 1 hexokinase.ConclusionOne-dimensional PAGE constitutes a simple, rapid, reliable, inexpensive method for analyzing proteins associated with sperm motility in individual human ejaculates.
Precision Trial Drawer, a Computational Tool to Assist Planning of Genomics-Driven Trials in Oncology
Authors: Melloni Giorgio E.M. , Guida Alessandro , Curigliano Giuseppe , Botteri Edoardo , Esposito Angela , Kamal Maude , Le Tourneau Christoph , Riva Laura , Magi Alberto , de Maria Ruggero , Pelicci Piergiuseppe , Mazzarella Luca 
Published: August 2018

Purpose Trials that accrue participants on the basis of genetic biomarkers are a powerful means of testing targeted drugs, but they are often complicated by the rarity of the biomarker-positive population. Umbrella trials circumvent this by testing multiple hypotheses to maximize accrual. However, bigger trials have higher chances of conflicting treatment allocations because of the coexistence of multiple actionable alterations; allocation strategies greatly affect the efficiency of enrollment and should be carefully planned on the basis of relative mutation frequencies, leveraging information from large sequencing projects. Methods We developed software named Precision Trial Drawer (PTD) to estimate parameters that are useful for designing precision trials, most importantly, the number of patients needed to molecularly screen (NNMS) and the allocation rule that maximizes patient accrual on the basis of mutation frequency, systematically assigning patients with conflicting allocations to the drug associated with the rarer mutation. We used data from The Cancer Genome Atlas to show their potential in a 10-arm imaginary trial of multiple cancers on the basis of genetic alterations suggested by the past Molecular Analysis for Personalised Therapy (MAP) conference. We validated PTD predictions versus real data from the SHIVA (A Randomized Phase II Trial Comparing Therapy Based on Tumor Molecular Profiling Versus Conventional Therapy in Patients With Refractory Cancer) trial. Results In the MAP imaginary trial, PTD-optimized allocation reduces number of patients needed to molecularly screen by up to 71.8% (3.5 times) compared with nonoptimal trial designs. In the SHIVA trial, PTD correctly predicted the fraction of patients with actionable alterations (33.51% [95% CI, 29.4% to 37.6%] in imaginary v 32.92% [95% CI, 28.2% to 37.6%] expected) and allocation to specific treatment groups (RAS/MEK, PI3K/mTOR, or both). Conclusion PTD correctly predicts crucial parameters for the design of multiarm genetic biomarker-driven trials. PTD is available as a package in the R programming language and as an open-access Web-based app. It represents a useful resource for the community of precision oncology trialists. The Web-based app is available at https://gmelloni.github.io/ptd/shinyapp.html .
β-Cell Dedifferentiation in Patients With T2D With Adequate Glucose Control and Nondiabetic Chronic Pancreatitis
Authors: Sun Jiajun , Ni Qicheng , Xie Jing , Xu Min , Zhang Jun , Kuang Jie , Wang Yanqiu , Ning Guang , Wang Qidi 
Published: August 2018

AbstractContextType 2 diabetes (T2D) and pancreatogenic diabetes are both associated with loss of functional β-cell mass. Previous studies have proposed β-cell dedifferentiation as a mechanism of islet β-cell failure, but its significance in humans is still controversial.ObjectiveTo determine whether β-cell dedifferentiation occurs in human T2D with adequate glucose control and in nondiabetic chronic pancreatitis (NDCP), we examined pancreatic islets from nine nondiabetic controls, 10 patients with diabetes with well-controlled fasting glycemia, and four individuals with NDCP.DesignWe calculated the percentage of hormone-negative endocrine cells and multihormone endocrine cells and scored the pathological characteristics; that is, inflammatory cell infiltration, fibrosis, atrophy, and steatosis, in each case.ResultsWe found a nearly threefold increase in dedifferentiated cells in T2D with adequate glucose control compared with nondiabetic controls (10.0% vs 3.6%, T2D vs nondiabetic controls, P &lt; 0.0001). The dedifferentiation rate was positively correlated with the duration of diabetes. Moreover, we detected a considerable proportion of dedifferentiated cells in NDCP (10.4%), which correlated well with the grade of inflammatory cell infiltration, fibrosis, and atrophy.ConclusionsThe data support the view that pancreatic β-cells are dedifferentiated in patients with T2D with adequate glucose control. Furthermore, the existence of abundant dedifferentiated cells in NDCP suggests that inflammation-induced β-cell dedifferentiation can be a cause of pancreatogenic diabetes during disease progress.
Cluster Headache and Other Trigeminal Autonomic Cephalalgias
Authors: Burish Mark 
Published: August 2018

ABSTRACT

PURPOSE OF REVIEW
This article covers the clinical features, differential diagnosis, and management of the trigeminal autonomic cephalalgias (TACs). The TACs are composed of five diseases: cluster headache, paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT), short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA), and hemicrania continua.

RECENT FINDINGS
New classifications for the TACs have two important updates; chronic cluster headache is now defined as remission periods lasting less than 3 months (formerly less than 1 month), and hemicrania continua is now classified as a TAC (formerly classified as other primary headache). The first-line treatments of TACs have not changed in recent years: cluster headache is managed with oxygen, triptans, and verapamil; paroxysmal hemicrania and hemicrania continua are managed with indomethacin; and SUNCT and SUNA are managed with lamotrigine. However, advancements in neuromodulation have recently provided additional options for patients with cluster headache, which include noninvasive devices for abortive therapy and invasive devices for refractory cluster headache. Patient selection for these devices is key.

SUMMARY
The TACs are a group of diseases that appear similar to each other and to other headache disorders but have important differences. Proper diagnosis is crucial for proper treatment. This article reviews the pathophysiology, epidemiology, differential diagnosis, and treatment of the TACs.
Cranial Neuralgias
Authors: Tepper Stewart J. 
Published: August 2018

ABSTRACT

PURPOSE OF REVIEW
This article describes the clinical features and diagnostic criteria, pathophysiology (when known), and treatment strategies of the major cranial neuralgias.

RECENT FINDINGS
Abnormal vascular loops compressing cranial nerves are the most common known pathogenesis associated with the primary neuralgias.

SUMMARY
The most frequently encountered primary neuralgias are trigeminal neuralgia, occipital neuralgia, and, rarely, glossopharyngeal neuralgia. Nervus intermedius neuralgia is even more rare. All neuralgias merit a careful workup for secondary causes. Drug treatment generally relies on antiepileptic drugs, antidepressants, and baclofen. OnabotulinumtoxinA can be useful in treating some cranial neuralgias. Surgical and invasive treatments include ablation, gamma knife treatment, and microvascular decompression.
Pediatric and Adolescent Headache
Authors: Gelfand Amy A. 
Published: August 2018

ABSTRACTPURPOSE OF REVIEWThis article provides the practicing neurologist with a comprehensive, evidence-based approach to the diagnosis and management of headache in children and adolescents, with a focus on migraine.RECENT FINDINGSFour triptans are now labeled by the US Food and Drug Administration (FDA) for acute migraine treatment in adolescents, and rizatriptan is labeled for use in children age 6 and older. For preventive migraine treatment, the Childhood and Adolescent Migraine Prevention trial demonstrated that approximately 60% of children and adolescents with migraine will improve with a three-pronged treatment approach that includes: (1) lifestyle management counseling (on sleep, exercise, hydration, caffeine, and avoidance of meal skipping); (2) optimally dosed acute therapy, specifically nonsteroidal anti-inflammatory drugs and triptans; and (3) a preventive treatment that has some evidence for efficacy. For the remaining 40% of children and adolescents, and for those who would not have qualified for the Childhood and Adolescent Migraine Prevention trial because of having continuous headache or medication-overuse headache, the clinician’s judgment remains the best guide to preventive therapy selection.SUMMARYRandomized placebo-controlled trials have been conducted to guide first-line acute and preventive migraine treatments in children and adolescents. Future research is needed to guide treatment for those with more refractory migraine, as well as for children and adolescents who have other primary headache disorders.
Secondary Headache Syndromes
Authors: Chou Denise E. 
Published: August 2018

ABSTRACT

PURPOSE OF REVIEW
This article is intended to assist clinicians in distinguishing benign primary headache syndromes from serious headache presentations that arise from exogenous causes.

RECENT FINDINGS
Although most cases of severe headache are benign, it is essential to recognize the signs and symptoms of potentially life-threatening conditions. Patients with primary headache disorders can also acquire secondary conditions that may present as a change in their baseline headache patterns and characteristics. Clinical clues in the history and examination can help guide the diagnosis and management of secondary headache disorders. Furthermore, advances in the understanding of basic mechanisms of headache may offer insight into the proposed pathophysiology of secondary headaches.

SUMMARY
Several structural, vascular, infectious, inflammatory, and traumatic causes of headache are highlighted. Careful history taking and examination can enable prompt identification and treatment of underlying serious medical disorders causing secondary headache syndromes.
Headache in Pregnancy
Authors: Robbins Matthew S. 
Published: August 2018

ABSTRACT

PURPOSE OF REVIEW
Headache disorders are extraordinarily common and disproportionately impact women of childbearing age. This article reviews the importance of proper diagnosis, natural history, and management of headache disorders in pregnant and postpartum women.

RECENT FINDINGS
Red flags for secondary headache specifically among pregnant women include elevated blood pressure and lack of a previous headache history, as well as a prolonged duration of the headache attack in those with a prior history of migraine. Migraine improvement is typical for most pregnant women, but the prognosis for women who have migraine with aura or chronic migraine is less predictable. Migraine is now an established risk factor for the development of preeclampsia. Recent data suggest hazards for compounds containing butalbital and possibly a better safety profile for triptans than previously believed during pregnancy. Peripheral nerve blocks and noninvasive neurostimulation devices are procedural and emerging therapies that have promising safety profiles for pregnant women with headache disorders.

SUMMARY
Acute headache occurring in pregnancy and the postpartum period is a red flag requiring diagnostic vigilance. Migraine frequency in women typically improves during pregnancy, although this trend is less certain when aura is present and after delivery. Acute and preventive treatment plans during pregnancy and lactation are plausible but may require shifts in therapeutic hierarchy. Relatively safe oral, parenteral, and procedural therapies are available for pregnant women. Noninvasive neuromodulation devices are already available and will likely play a greater role in the coming years. Migraine is associated with medical and obstetrical complications during pregnancy, and women with frequent migraine attacks may need to be considered high risk.
The interplay between exosomes and autophagy – partners in crime
Authors: Xu Jing , Camfield Robert , Gorski Sharon M. 
Published: August 2018

ABSTRACT
The eukaryotic endomembrane system is a complex series of interconnected membranous organelles that play important roles in responding to stress and maintaining cell homeostasis during health and disease. Two components of this system, exosome biogenesis and autophagy, are linked by the endolysosomal pathway. Exosomes are cargo-laden extracellular vesicles that arise from endosome-derived multivesicular bodies, and autophagy is a lysosomal-dependent degradation and recycling pathway. Recent studies have revealed shared molecular machinery between exosome biogenesis and autophagy, as well as substantial crosstalk between these two processes. In this Review, we first describe the classic view of exosome biogenesis and autophagy, including their links to the endolysosomal pathway. We then present the evidence for autophagy-related proteins in exosome biogenesis, the emerging roles of amphisomes and the evolving models of exosome-autophagy pathway interactions. Finally, we discuss the implications of exosome and autophagy interplay in the context of neurodegeneration and cancer.
De novo whole-genome assembly of a wild type yeast isolate using nanopore sequencing
Authors: Liem Michael , Jansen Hans J. , Dirks Ron P. , Henkel Christiaan V. , van Heusden G. Paul H. , Lemmers Richard J.L.F. , Omer Trifa , Shao Shuai , Punt Peter J. , Spaink Herman P. 
Published: August 2018

Background: The introduction of the MinION sequencing device by Oxford Nanopore Technologies may greatly accelerate whole genome sequencing. Nanopore sequence data offers great potential for de novo assembly of complex genomes without using other technologies. Furthermore, Nanopore data combined with other sequencing technologies is highly useful for accurate annotation of all genes in the genome. In this manuscript we used nanopore sequencing as a tool to classify yeast strains. Methods: We compared various technical and software developments for the nanopore sequencing protocol, showing that the R9 chemistry is, as predicted, higher in quality than R7.3 chemistry. The R9 chemistry is an essential improvement for assembly of the extremely AT-rich mitochondrial genome. We double corrected assemblies from four different assemblers with PILON and assessed sequence correctness before and after PILON correction with a set of 290 Fungi genes using BUSCO. Results: In this study, we used this new technology to sequence and de novo assemble the genome of a recently isolated ethanologenic yeast strain, and compared the results with those obtained by classical Illumina short read sequencing. This strain was originally named Candida vartiovaarae (Torulopsis vartiovaarae) based on ribosomal RNA sequencing. We show that the assembly using nanopore data is much more contiguous than the assembly using short read data. We also compared various technical and software developments for the nanopore sequencing protocol, showing that nanopore-derived assemblies provide the highest contiguity. Conclusions: The mitochondrial and chromosomal genome sequences showed that our strain is clearly distinct from other yeast taxons and most closely related to published Cyberlindnera species. In conclusion, MinION-mediated long read sequencing can be used for high quality de novo assembly of new eukaryotic microbial genomes.
The Congress Impact Factor: A proposal from board members of the World Society of Emergency Surgeons.it (WSES) and Academy of Emergency Medicine and Care (AcEMC)
Authors: De Simone Belinda , Ansaloni Luca , Kelly Micheal Denis , Coccolini Federico , Sartelli Massimo , Di Saverio Salomone , Pisano Michele , Cervellin Gianfranco , Baiocchi Gianluca , Catena Fausto 
Published: August 2018

Many scientific congresses and conferences are held every year around the world. The aim of the World Society of Emergency Surgeons.it (WSES) and Academy of Emergency Medicine and Care (AcEMC) was to develop a simple mathematical parameter as an indicator of academic quality and scientific validity of a congress. In this opinion article, a new metric, the Congress Impact Factor (IFc), is proposed taking into consideration the widely used Impact Factor as an indicator of journals’ prestige and using H-index analysis. The IFc is derived from the mathematical ratio between the mean H-index of invited lecturers normalized for lecture topic and number of lectures in the conference. In case of multiple sessions, the mean of all IFc is calculated along with its standard deviation. We conclude that the IFc can be a useful measure for evaluating and comparing congress prestige, and may also represent a potentially useful parameter for improving academic curriculum and helping participants to choose the more prestigious meetings for their education.
Androgen-dependent alternative mRNA isoform expression in prostate cancer cells
Authors: Munkley Jennifer , Maia Teresa M. , Ibarluzea Nekane , Livermore Karen E. , Vodak Daniel , Ehrmann Ingrid , James Katherine , Rajan Prabhakar , Barbosa-Morais Nuno L. , Elliott David J. 
Published: August 2018

Background: Androgen steroid hormones are key drivers of prostate cancer. Previous work has shown that androgens can drive the expression of alternative mRNA isoforms as well as transcriptional changes in prostate cancer cells. Yet to what extent androgens control alternative mRNA isoforms and how these are expressed and differentially regulated in prostate tumours is unknown. Methods: Here we have used RNA-Seq data to globally identify alternative mRNA isoform expression under androgen control in prostate cancer cells, and profiled the expression of these mRNA isoforms in clinical tissue. Results: Our data indicate androgens primarily switch mRNA isoforms through alternative promoter selection. We detected 73 androgen regulated alternative transcription events, including utilisation of 56 androgen-dependent alternative promoters, 13 androgen-regulated alternative splicing events, and selection of 4 androgen-regulated alternative 3′ mRNA ends. 64 of these events are novel to this study, and 26 involve previously unannotated isoforms. We validated androgen dependent regulation of 17 alternative isoforms by quantitative PCR in an independent sample set. Some of the identified mRNA isoforms are in genes already implicated in prostate cancer (including LIG4, FDFT1 and RELAXIN), or in genes important in other cancers (e.g. NUP93 and MAT2A). Importantly, analysis of transcriptome data from 497 tumour samples in the TGCA prostate adenocarcinoma (PRAD) cohort identified 13 mRNA isoforms (including TPD52, TACC2 and NDUFV3) that are differentially regulated in localised prostate cancer relative to normal tissue, and 3 (OSBPL1A, CLK3 and TSC22D3) which change significantly with Gleason grade and tumour stage. Conclusions: Our findings dramatically increase the number of known androgen regulated isoforms in prostate cancer, and indicate a highly complex response to androgens in prostate cancer cells that could be clinically important.
A pilot study on assessing the role of intra-operative Flow 800 vascular map model in predicting onset of vasospasm following micro vascular clipping of ruptured intracranial aneurysms
Authors: Munakomi Sunil , Poudel Deepak 
Published: August 2018

Objective To ascertain the predictive value of intra-operative FLOW 800 vascular map model in predicting onset of post-operative clinical vasospasm and delayed cerebral ischemia among patients undergoing micro-vascular clipping of ruptured intracranial aneurysms. Material and methods A total of 40 patients were enrolled in the study and their variables such as age, World Federation of Neurological Surgeons (WFNS) grade at presentation, Computerized Tomography (CT) Fisher grading, location of the aneurysms, and Indocyanine Green (ICG) flow status were compared and statistically analyzed along with differences in Absorption Intensities (AI) and difference in time lag values obtained from the FLOW 800 vascular map studies for predicting onset of vasospasm. Results The Receiver Operating curve (ROC) of the model for predicting post-operative vasospasm was highest (.892) for difference in the AI followed by CT Fisher grading (.778), difference in time lag (.700) and WFNS grading (.699).Analysis of variance for different variables studied in our model for predicting vasospasm was significant for all except for age (.991) and the ICG flow through the parent vessel (.079).Multivariate analysis done for predicting the vasospasm was significant for all variables except for age (.869) and ICG main flow (.196) Conclusion Our study confirmed the role of FLOW 800 study model in predicting clinical vasospasm. Inclusion of this entity would therefore help in taking timely and correct therapeutics measures to ensure better patient outcomes.