bluuebunny/crossref_metadata_2025_split huggingface dataset:
Very high‐frequency oscillations: Novel biomarkers of the epileptogenic zone
Authors: Brázdil Milan , Pail Martin , Halámek Josef , Plešinger Filip , Cimbálník Jan , Roman Robert , Klimeš Petr , Daniel Pavel , Chrastina Jan , Brichtová Eva , Rektor Ivan , Worrell Gregory A. , Jurák Pavel 
Published: August 2017

ObjectiveIn the present study, we aimed to investigate depth electroencephalographic (EEG) recordings in a large cohort of patients with drug‐resistant epilepsy and to focus on interictal very high‐frequency oscillations (VHFOs) between 500Hz and 2kHz. We hypothesized that interictal VHFOs are more specific biomarkers for epileptogenic zone compared to traditional HFOs.MethodsForty patients with focal epilepsy who underwent presurgical stereo‐EEG (SEEG) were included in the study. SEEG data were recorded with a sampling rate of 25kHz, and a 30‐minute resting period was analyzed for each patient. Ten patients met selected criteria for analyses of correlations with surgical outcome: detection of interictal ripples (Rs), fast ripples (FRs), and VHFOs; resective surgery; and at least 1 year of postoperative follow‐up. Using power envelope computation and visual inspection of power distribution matrixes, electrode contacts with HFOs and VHFOs were detected and analyzed.ResultsInterictal very fast ripples (VFRs; 500–1,000Hz) were detected in 23 of 40 patients and ultrafast ripples (UFRs; 1,000–2,000Hz) in almost half of investigated subjects (n = 19). VFRs and UFRs were observed only in patients with temporal lobe epilepsy and were recorded exclusively from mesiotemporal structures. The UFRs were more spatially restricted in the brain than lower‐frequency HFOs. When compared to R oscillations, significantly better outcomes were observed in patients with a higher percentage of removed contacts containing FRs, VFRs, and UFRs.InterpretationInterictal VHFOs are relatively frequent abnormal phenomena in patients with epilepsy, and appear to be more specific biomarkers for epileptogenic zone when compared to traditional HFOs. Ann Neurol 2017;82:299–310
Nickel‐Catalyzed Conjugate Addition of Silyl Ketene Imines to In Situ Generated Indol‐2‐ones: Highly Enantioselective Construction of Vicinal All‐Carbon Quaternary Stereocenters
Authors: Zheng Jianfeng , Lin Lili , Dai Li , Tang Qiong , Liu Xiaohua , Feng Xiaoming 
Published: August 2017

AbstractThe first enantioselective conjugate addition of silyl ketene imines to in situ generated indol‐2‐ones was performed in the presence of a chiral N,N′‐dioxide/NiII catalyst. This method provides efficient access to chiral β‐alkyl nitriles bearing congested vicinal all‐carbon quaternary stereocenters in up to 90 % yield with 23:1 d.r. and 98 % ee. The products enable facile transformations to chiral pyrroloindoline frameworks and spirocyclohexane oxindole derivatives. A possible transition state was also proposed to explain the origin of the asymmetric induction.
Rhodium‐Catalyzed [2+2+2] Cycloaddition Reactions of Linear Allene–Ene–Ynes to afford Fused Tricyclic Scaffolds: Insights into the Mechanism
Authors: Cassú Daniel , Parella Teodor , Solà Miquel , Pla‐Quintana Anna , Roglans Anna 
Published: August 2017

AbstractAllene‐(E)‐ene‐yne N‐tosyl‐tethered substrates 3 a–3 h were efficiently prepared and their rhodium‐catalyzed [2+2+2] cycloaddition reactions were evaluated. The cycloadditions are chemoselective as only the proximal double bond of the allene reacted to afford exocyclic double bonds in the fused‐tricyclic scaffolds. The stereoselectivity depended on the catalytic system used. Reactivity between allene, alkene, and alkyne was studied for the first time by density functional theory calculations. This mechanistic study determines the order in which the unsaturated groups take part in the catalytic cycle.
Mangrove microclimates alter seedling dynamics at the range edge
Authors: Devaney John L. , Lehmann Michael , Feller Ilka C. , Parker John D. 
Published: August 2017

AbstractRecent climate warming has led to asynchronous species migrations, with major consequences for ecosystems worldwide. In woody communities, localized microclimates have the potential to create feedback mechanisms that can alter the rate of species range shifts attributed to macroclimate drivers alone. Mangrove encroachment into saltmarsh in many areas is driven by a reduction in freeze events, and this encroachment can further modify local climate, but the subsequent impacts on mangrove seedling dynamics are unknown. We monitored microclimate conditions beneath mangrove canopies and adjacent open saltmarsh at a freeze‐sensitive mangrove‐saltmarsh ecotone and assessed survival of experimentally transplanted mangrove seedlings. Mangrove canopies buffered night time cooling during the winter, leading to interspecific differences in freeze damage on mangrove seedlings. However, mangrove canopies also altered biotic interactions. Herbivore damage was higher under canopies, leading to greater mangrove seedling mortality beneath canopies relative to saltmarsh. While warming‐induced expansion of mangroves can lead to positive microclimate feedbacks, simultaneous fluctuations in biotic drivers can also alter seedling dynamics. Thus, climate change can drive divergent feedback mechanisms through both abiotic and biotic channels, highlighting the importance of vegetation‐microclimate interactions as important moderators of climate driven range shifts.
Living rain gauges: cumulative precipitation explains the emergence schedules of California protoperiodical cicadas
Authors: Chatfield‐Taylor Will , Cole Jeffrey A. 
Published: August 2017

AbstractMass multi‐species cicada emergences (broods) occur in California with variable periodicity. Here we present the first rule set that predicts the emergence of protoperiodical cicada communities. We tested two hypotheses with a dataset consisting of direct observations and georeferenced museum specimen records: first, that cicada broods are triggered to emerge by periodic ENSO events and second, that brood emergences occur after precipitation accumulates above a threshold value. The period of ENSO events does not explain the observed pattern of cicada brood emergence. Rather, broods emerged given two conditions: (1) that total precipitation exceeded a threshold of 1,181 mm, and (2) that a minimum 3‐yr period lapsed. The precipitation threshold is obeyed over an 800 km north‐south distance in California and across a variety of habitats. We predict the next brood emergence at one study site in arid Los Angeles County desert foothills to occur in 2020 or, if drought conditions continue, in 2021.
Bottom‐up processes influence the demography and life‐cycle phenology of Hawaiian bird communities
Authors: Wolfe Jared D. , Ralph C. John , Wiegardt Andrew 
Published: August 2017

AbstractChanges in climate can indirectly regulate populations at higher trophic levels by influencing the availability of food resources in the lower reaches of the food web. As such, species that rely on fruit and nectar food resources may be particularly sensitive to these bottom‐up perturbations due to the strength of their trophic linkages with climatically‐influenced plants. To measure the influence of climatically‐mediated, bottom‐up processes, we used climate, bird capture, bird count, and plant phenology data from the Big Island of Hawaii to construct a series of structural equation and abundance models. Our results suggest that fruit and nectar‐eating birds arrange life cycle events around climatically‐influenced food resources, while some of these same food resources also influence seasonal patterns of abundance. This trend was particularly strong for two native nectarivores, ‘I'iwi and ‘Apapane, where we found that the dissimilar timing of molting and breeding activity was associated with peak abundance of the two most common flowers at our study site which, in turn, were each driven by dissimilar climatic cues. Given the rapidly changing Hawaiian climate, we suggest that determining behavioral plasticity, or evolutionary capacity of birds to mitigate changes in climatically‐influenced food resources, should be recognized as a future research priority.
Blocking protein quality control to counter hereditary cancers
Authors: Kampmeyer Caroline , Nielsen Sofie V. , Clausen Lene , Stein Amelie , Gerdes Anne‐Marie , Lindorff‐Larsen Kresten , Hartmann‐Petersen Rasmus 
Published: August 2017

AbstractInhibitors of molecular chaperones and the ubiquitin‐proteasome system have already been clinically implemented to counter certain cancers, including multiple myeloma and mantle cell lymphoma. The efficacy of this treatment relies on genomic alterations in cancer cells causing a proteostatic imbalance, which makes them more dependent on protein quality control (PQC) mechanisms than normal cells. Accordingly, blocking PQC, e.g. by proteasome inhibitors, may cause a lethal proteotoxic crisis in cancer cells, while leaving normal cells unaffected. Evidence, however, suggests that the PQC system operates by following a better‐safe‐than‐sorry principle and is thus prone to target proteins that are only slightly structurally perturbed, but still functional. Accordingly, implementing PQC inhibitors may also, through an entirely different mechanism, hold potential for other cancers. Several inherited cancer susceptibility syndromes, such as Lynch syndrome and von Hippel‐Lindau disease, are caused by missense mutations in tumor suppressor genes, and in some cases, the resulting amino acid substitutions in the encoded proteins cause the cellular PQC system to target them for degradation, although they may still retain function. As a consequence of this over‐meticulous PQC mechanism, the cell may end up with an insufficient amount of the abnormal, but functional, protein, which in turn leads to a loss‐of‐function phenotype and manifestation of the disease. Increasing the amounts of such proteins by stabilizing with chemical chaperones, or by targeting molecular chaperones or the ubiquitin‐proteasome system, may thus avert or delay the disease onset. Here, we review the potential of targeting the PQC system in hereditary cancer susceptibility syndromes.
Cytotoxicity evaluation of unfunctionalized multiwall carbon nanotubes‐ultrahigh molecular weight polyethylene nanocomposites
Authors: Mamidi Narsimha , Leija Héctor Manuel , Diabb Jose Manuel , Lopez Romo Irasema , Hernandez Diana , Castrejón Javier Villela , Martinez Romero Oscar , Barrera Enrique V. , Elias Zúñiga Alex 
Published: August 2017

AbstractThe carbon nanotubes were chosen for this study since long, small to medium diameter, and unfunctionalized nanotubes are considered less favorable for nontoxic applications. The intent of the study is to expand the use of CNTs beyond current understood nontoxic means. Multiwall carbon nanotube/ultrahigh molecular weight polyethylene (MWCNT/UHMWPE) nanocomposites were prepared by reinforcing long chain UHMWPE with MWCNTs. These nanocomposites were prepared to study their cytotoxicity assessments with human fibroblast cell lines. Cell adhesion, proliferation, and differentiation were studied with human fibroblast cell lines. In vitro studies revealed good cell viability on the surface of MWCNT/UHMWPE composites even after 72 h. The nanocomposites showed better cell attachment for fibroblasts than pristine UHMWPE. Overall, the results showed that MWCNT/UHMWPE composites displayed good cellular growth and biocompatibility indicating another way CNTs can be nontoxic. These nanocomposites offer nontoxic conditions that can be used in biomedical devices because the long chain UHMWPE is entangled with long MWCNTs. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3042–3049, 2017.
Bending of the BST‐2 coiled‐coil during viral budding
Authors: Ozcan Kadir A. , Berndsen Christopher E. 
Published: August 2017

AbstractBST‐2/tetherin is a human extracellular transmembrane protein that serves as a host defense factor against HIV‐1 and other viruses by inhibiting viral spreading. Structurally, BST‐2 is a homo‐dimeric coiled‐coil that is connected to the host cell membrane by N and C terminal transmembrane anchors. The C‐terminal membrane anchor of BST‐2 is inserted into the budding virus while the N‐terminal membrane anchor remains in the host cell membrane creating a viral tether. The structural mechanism of viral budding and tethering as mediated by BST‐2 is not clear. To more fully describe the mechanism of viral tethering, we created a model of BST‐2 embedded in a membrane and used steered molecular dynamics to simulate the transition from the host cell membrane associated form to the cell‐virus membrane bridging form. We observed that BST‐2 did not transition as a rigid structure, but instead bent at positions with a reduced interface between the helices of the coiled‐coil. The simulations for the human BST‐2 were then compared with simulations on the mouse homolog, which has no apparent weak spots. We observed that the mouse homolog spread the bending across the ectodomain, rather than breaking at discrete points as observed with the human homolog. These simulations support previous biochemical and cellular work suggesting some flexibility in the coiled‐coil is necessary for viral tethering, while also highlighting how subtle changes in protein sequence can influence the dynamics and stability of proteins with overall similar structure.
Many interspecific chromosomal introgressions are highly prevalent in Holarctic Saccharomyces uvarum strains found in human‐related fermentations
Authors: Albertin Warren , Chernova Maria , Durrens Pascal , Guichoux Erwan , Sherman David James , Masneuf‐Pomarede Isabelle , Marullo Philippe 
Published: August 2017

AbstractIn the last two decades, the extensive genome sequencing of strains belonging to the Saccharomyces genus has revealed the complex reticulated evolution of this group. Among the various evolutionary mechanisms described, the introgression of large chromosomal regions resulting from interspecific hybridization has recently shed light on Saccharomyces uvarum species. In this work we provide the de novo assembled genomes of four S. uvarum strains presenting more than 712 kb of introgressed loci inherited from both Saccharomyces eubayanus and Saccharomyces kudriavzevii species. In order to study the prevalence of such introgressions in a large population, we designed multiplexed PCR markers able to survey the inheritance of eight chromosomal regions. Our data confirm that introgressions are widely disseminated in Holarctic S. uvarum populations and are more frequently found in strains isolated from human‐related fermentations. According to the origin of the strains (nature or cider‐ or wine‐related processes), some loci are over‐represented, suggesting their positive selection by human activity. Except for one locus located on chromosome 7, the introgressions present a low level of heterozygozity similar to that observed for nine neutral markers (microsatellites). Finally, most of the loci tested showed an expected Mendelian segregation after meiosis and can recombine with their chromosomal counterpart in S. uvarum. Copyright © 2017 John Wiley & Sons, Ltd.
FDA Approval of PARP Inhibitors and the Impact on Genetic Counseling and Genetic Testing Practices
Authors: Buchtel Kathryn M. , Vogel Postula Kristen J. , Weiss Shelly , Williams Carmen , Pineda Mario , Weissman Scott M. 
Published: August 2017

AbstractIn December 2014, the FDA approved olaparib, a poly(ADP‐ribose) polymerase inhibitor (PARPi) for ovarian cancer patients who have failed three or more lines of chemotherapy and have a germline BRCA1/2 mutation identified through a companion diagnostic test (BRACAnalysis CDx™ (CDx™)) offered exclusively by Myriad Genetic Laboratories. This study explored the impact of PARPi/CDx™ on genetic counselors’ (GCs) counseling and testing practices. One hundred twenty three GCs responded to an online survey regarding pre‐ and post‐FDA approval referral patterns, testing strategies/influences, and anecdotal experiences with insurance coverage of PARPi for BRCA1/2 positive patients through a non‐CDx™ platform. Following PARPi approval, 40% of respondents reported an increase in overall referrals of ovarian cancer patients and 20% had an increase in post‐test counseling only referrals. The majority (61.9%) of respondents reported no change in genetic testing strategy, and there was no change in factors influencing choice of testing laboratory. Nearly all (98.1%) respondents who had experience with insurance covering PARPi indicated approval with mutations identified via non‐CDx™ testing. Respondents indicated an increase in referral volume following FDA approval of PARPi/CDx™, but did not report changes in testing practices. Respondents were not aware of PARPi insurance coverage denial in the absence of CDx™.
The outcomes of glucose abnormalities in chronic hepatitis C patients receiving interferon‐free direct antiviral agents
Authors: Huang Jee‐Fu , Huang Chung‐Feng , Yeh Ming‐Lun , Dai Chia‐Yen , Hsieh Meng‐Hsuan , Yang Jeng‐Fu , Huang Ching‐I. , Lin Yi‐Hung , Liang Po‐Cheng , Lin Zu‐Yau , Chen Shinn‐Chern , Yu Ming‐Lung , Chuang Wan‐Long 
Published: August 2017

AbstractDirect‐acting antiviral agents (DAAs) have been widely used for chronic hepatitis C (CHC) treatment recently. The characteristics of glucose abnormalities after DAAs therapy however, remain elusive. We aimed to elucidate the mutual impact between treatment response and parameters of glucose abnormalities after DAAs therapy in CHC patients. CHC patients who received DAAs therapy were recruited. The primary outcome measurements were their insulin resistance (IR) and beta‐cell function assessed by the homeostasis model assessment (HOMA) method before treatment and at end‐of‐follow‐up (EOF). Sixty‐five CHC patients (19 males, mean age = 59.8 ± 10.3 years) were consecutively enrolled. They included 47 (72.3%) patients of genotype‐1 infection. The treatment regimens among patients were sofosbuvir in 30 patients, paritaprevir‐ritonavir/ombitasvir/dasabuvir in 23 patients, and asunaprevir/daclatasvir in 12 patients respectively. The overall sustained virological response rate was 98.5%. The mean IR at EOF was 2.6 ± 1.8, which was not significantly different from baseline level (2.7 ± 2.9, P = 0.75). There was a significant improvement of beta‐cell function at EOF compared to baseline (107.7 ± 86.8 to 86.7 ± 44.5, P = 0.05). The amelioration of beta‐cell function at EOF was significantly observed among 23 patients of high baseline IR (166.7 ± 111.3 of baseline vs 105.7 ± 48.2 of EOF, P = 0.04). Six (60%) of the 10 pre‐diabetic patients at baseline achieved a normoglycemic state at EOF. Successful eradication of HCV by DAAs might improve glucose abnormalities in CHC patients, particularly among those who had high IR.
Vonoprazan treatment improves gastrointestinal symptoms in patients with gastroesophageal reflux disease
Authors: Shinozaki Satoshi , Osawa Hiroyuki , Hayashi Yoshikazu , Sakamoto Hirotsugu , Miura Yoshimasa , Lefor Alan Kawarai , Yamamoto Hironori 
Published: August 2017

AbstractThe effects of vonoprazan, a new potassium‐competitive acid blocker, on gastroesophageal reflux disease (GERD) symptom are not fully elucidated. The aim of this study is to determine the effect of vonoprazan on GERD and associated gastrointestinal symptoms. We retrospectively reviewed 88 Helicobacter pylori negative patients with GERD treated with vonoprazan 10 mg daily. Symptoms were evaluated using the Izumo scale, which reflects quality of life related to various abdominal symptoms. The rates of improvement and resolution of GERD symptoms were 86% (76/88) and 57% (50/88), respectively. Improvement and resolution in patients with erosive esophagitis was higher than in those with non‐erosive reflux disease (91% vs 83%, p = 0.260 and 71% vs 47%, p = 0.025, respectively). We attempted to identify factors which predict the effects of vonoprazan. Multivariate analysis identified advanced age (≥60‐year‐old) (odds ratio [OR] 7.281, 95% confidence interval [CI] 2.056–25.776, p = 0.002), obesity (BMI ≥ 24) (OR 3.342, 95%CI 1.124–9.940, p = 0.030) and erosive esophagitis (OR 4.368, 95%CI 1.281–14.895, p = 0.018) as positive predictors of resolution of GERD symptoms. Alcohol use (OR 0.131, 95%CI 0.027–0.632, p = 0.011) and history of H. pylori eradication (OR 0.171, 95%CI 0.041–0.718, p = 0.015) were identified as negative predictors. Vonoprazan also improved epigastric pain (73%), postprandial distress (60%), constipation (58%) and diarrhea (52%) in patients with GERD. In conclusion, vonoprazan 10 mg daily is effective in improving GERD symptoms. Advanced age, obesity, erosive esophagitis, alcohol use and history of H. pylori eradication influence the resolution of GERD symptoms. Treatment with vonoprazan favorably affects gastrointestinal symptoms in patients with GERD.
Neuropsychiatric signs and symptoms of Alzheimer's disease: New treatment paradigms
Authors: Lanctôt Krista L. , Amatniek Joan , Ancoli‐Israel Sonia , Arnold Steven E. , Ballard Clive , Cohen‐Mansfield Jiska , Ismail Zahinoor , Lyketsos Constantine , Miller David S. , Musiek Erik , Osorio Ricardo S. , Rosenberg Paul B. , Satlin Andrew , Steffens David , Tariot Pierre , Bain Lisa J. , Carrillo Maria C. , Hendrix James A. , Jurgens Heidi , Boot Brendon 
Published: August 2017

AbstractNeuropsychiatric symptoms (NPSs) are hallmarks of Alzheimer's disease (AD), causing substantial distress for both people with dementia and their caregivers, and contributing to early institutionalization. They are among the earliest signs and symptoms of neurocognitive disorders and incipient cognitive decline, yet are under‐recognized and often challenging to treat. With this in mind, the Alzheimer's Association convened a Research Roundtable in May 2016, bringing together experts from academia, industry, and regulatory agencies to discuss the latest understanding of NPSs and review the development of therapeutics and biomarkers of NPSs in AD. This review will explore the neurobiology of NPSs in AD and specific symptoms common in AD such as psychosis, agitation, apathy, depression, and sleep disturbances. In addition, clinical trial designs for NPSs in AD and regulatory considerations will be discussed.
Soft‐switching bidirectional DC–DC converter with high voltage conversion ratio
Authors: Molavi Navid , Adib Ehsan , Farzanehfard Hosein 
Published: August 2017

This study introduces a soft‐switching non‐isolated bidirectional DC–DC converter with high voltage conversion ratio and low voltage stress across semiconductor devices. The presented topology is well suited for high step‐up/step‐down applications. By integrating coupled inductors and switched capacitors techniques, a high step‐up/step‐down voltage gain is achieved. Active clamp circuits are employed in both high step‐up and high step‐down operating states to recycle the leakage inductance energy and realise zero‐voltage‐switching condition for all switches to mitigate the switching losses and improve efficiency. Also, the reverse recovery problem of the body diodes is completely alleviated owing to zero‐current‐switching performance. The operation principles and theoretical analysis of proposed converter are presented in details. Finally, the experimental results of a 200 W prototype circuit are provided to confirm the validity of the proposed topology.