bluuebunny/crossref_metadata_2025_split huggingface dataset:
Major pathologic response and RAD51 predict survival in lung cancer patients receiving neoadjuvant chemotherapy
Authors: Pataer Apar , Shao Ruping , Correa Arlene M. , Behrens Carmen , Roth Jack A. , Vaporciyan Ara A. , Wistuba Ignacio I. , Swisher Stephen G. 
Published: April 2018

AbstractIn a previous study, we determined that major pathologic response (MPR) as indicated by the percentage of residual viable tumor cells predicted overall survival (OS) in patients with non‐small‐cell lung cancer (NSCLC) who received neoadjuvant chemotherapy. In this study, we assessed whether two genes and five protein biomarkers could predict MPR and OS in 98 patients with NSCLC receiving neoadjuvant chemotherapy. We collected formalin‐fixed, paraffin‐embedded specimens of resected NSCLC tumors from 98 patients treated with neoadjuvant chemotherapy. We identified mutations in KRAS and EGFR genes using pyrosequencing and examined the expression of protein markers VEGFR2, EZH2, ERCC1, RAD51, and PKR using immunohistochemistry. We assessed whether gene mutation status or protein expression was associated with MPR or OS. We observed that KRAS mutation tended to be associated with OS (P = .06), but EGFR mutation was not associated with OS. We found that patients with high RAD51 expression levels had a poorer prognosis than did those with low RAD51 expression. We also observed that RAD51 expression was associated with MPR. MPR and RAD51 expression were associated with OS in univariate and multivariate analyses (P = .04 and P = .02, respectively). Combination of MPR with RAD51 is a significant predictor of prognosis in patients with NSCLC who received neoadjuvant chemotherapy. We demonstrated that MPR or RAD51 expression was associated with OS in patients with NSCLC receiving neoadjuvant chemotherapy. Prediction of a patient's prognosis could be improved by combined assessment of MPR and RAD51 expression.
Leadless pacemaker implantation after transcatheter lead extraction in complex anatomy patient
Authors: De Regibus Valentina , Pardeo Antonino , Artale Paolo , Petretta Andrea , Filannino Pasquale , Iacopino Saverio 
Published: April 2018

Key Clinical MessageAfter transvenous lead extraction, leadless pacemaker might be a valid alternative to the traditional two‐step strategy including an active fixation leads temporary PM and subsequent contralateral permanent implantation in patients who are pacemaker‐dependent. Moreover, leadless PM might be of great importance in patients presenting with congenital vascular or cardiac abnormality.
Evolutionary and demographic processes shaping geographic patterns of genetic diversity in a keystone species, the African forest elephant (Loxodonta cyclotis)
Authors: Ishida Yasuko , Gugala Natalie A. , Georgiadis Nicholas J. , Roca Alfred L. 
Published: April 2018

AbstractThe past processes that have shaped geographic patterns of genetic diversity may be difficult to infer from current patterns. However, in species with sex differences in dispersal, differing phylogeographic patterns between mitochondrial (mt) and nuclear (nu) DNA may provide contrasting insights into past events. Forest elephants (Loxodonta cyclotis) were impacted by climate and habitat change during the Pleistocene, which likely shaped phylogeographic patterns in mitochondrial (mt) DNA that have persisted due to limited female dispersal. By contrast, the nuclear (nu) DNA phylogeography of forest elephants in Central Africa has not been determined. We therefore examined the population structure of Central African forest elephants by genotyping 94 individuals from six localities at 21 microsatellite loci. Between forest elephants in western and eastern Congolian forests, there was only modest genetic differentiation, a pattern highly discordant with that of mtDNA. Nuclear genetic patterns are consistent with isolation by distance. Alternatively, male‐mediated gene flow may have reduced the previous regional differentiation in Central Africa suggested by mtDNA patterns, which likely reflect forest fragmentation during the Pleistocene. In species like elephants, male‐mediated gene flow erases the nuclear genetic signatures of past climate and habitat changes, but these continue to persist as patterns in mtDNA because females do not disperse. Conservation implications of these results are discussed.
As temperature increases, predator attack rate is more important to survival than a smaller window of prey vulnerability
Authors: Pepi Adam , Grof‐Tisza Patrick , Holyoak Marcel , Karban Richard 
Published: April 2018

AbstractClimate change can have strong effects on species interactions and community structure. Temperature‐dependent effects on predator–prey interactions are a major mechanism through which these effects occur. To understand the net effects of predator attack rates and dynamic windows of prey vulnerability, we examined the impacts of temperature on the interaction of a caterpillar (Arctia virginalis) and its ant predator (Formica lasioides). We conducted field experiments to examine attack rates on caterpillars relative to temperature, ant abundance, and body size, and laboratory experiments to determine the effects of temperature on caterpillar growth. We modeled temperature‐dependent survival based on the integrated effects of temperature‐dependent growth and temperature‐ and size‐dependent predation. Attack rates on caterpillars increased with warming and ant recruitment, but decreased with caterpillar size. Caterpillar growth rates increased with temperature, narrowing the window of vulnerability. The model predicted that net caterpillar survival would decrease with temperature, suggesting that A. virginalis populations could be depressed with future climate warming. Theoretical work suggests that the net outcome of predator–prey interactions with increasing temperature depends on the respective responses of interacting species in terms of velocity across space, whereas the present study suggests the importance of effects of temperature on prey window of vulnerability, or “velocity” across time.
Elastocaloric Cooling on the Miniature Scale: A Review on Materials and Device Engineering
Authors: Bruederlin Florian , Bumke Lars , Chluba Christoph , Ossmer Hinnerk , Quandt Eckhard , Kohl Manfred 
Published: April 2018

AbstractThis Review covers the fundamentals of operation and scaling of elastocaloric cooling devices as well as current developments of elastocaloric shape‐memory alloy (SMA) films and the engineering of SMA film‐based cooling devices. Sputter‐deposited TiNiCuCo alloys showing ultra‐low fatigue enable unique functional properties such as tailored transformation temperature gradients. Two substantially different concepts for the development of elastocaloric cooling demonstrators are discussed. One concept relies on heat transfer by mechanical contact between the elastocaloric SMA film and solid heat sink and source elements. The second concept makes use of the heat transfer between the elastocaloric SMA film and a heat transfer fluid, including the advanced technology of active regeneration. Demonstrators based on a single SMA film reach device temperature spans of 14 K and a high specific cooling power of up to 18 W g−1. The performance characteristics are compared with other solid‐state caloric cooling technologies.
The Empirical Studies of China's Enterprise Bankruptcy Law: Problems and Improvements
Authors: Lin Shaowei 
Published: April 2018

AbstractOver the past 9 years since the implementation of China's Enterprise Bankruptcy Law in 2007, it has contributed to some measures of regulating market practice and rearrangement of market resources and has become an integral part in an improved legal system of China's market economy. However, a closer look at the effect of implementing the Enterprise Bankruptcy Law shows that the number of bankruptcy cases after its implementation, instead of increasing, has taken on a trend of decreasing. Even under the influence of the 2008 financial crisis, no significant increase in the number of Chinese bankrupt enterprises means that China's Bankruptcy Law failed to play its due role, leaving a large gap as desired. As such, this article aims to examine the problems arising from the implementation of the Bankruptcy Law and, taking this as guidance, probe into the reasons hidden behind and propose possible improvement measures. It is expected that the Bankruptcy Law would increasingly play a key role in the development of China's market economy, particularly under the current situation where Chinese government proposes to clean up zombie businesses. Copyright © 2018 INSOL International and John Wiley & Sons, Ltd.
Drug‐induced Proarrhythmia and Torsade de Pointes: A Primer for Students and Practitioners of Medicine and Pharmacy
Authors: Turner J. Rick , Rodriguez Ignacio , Mantovani Emily , Gintant Gary , Kowey Peter R. , Klotzbaugh Ralph J. , Prasad Krishna , Sager Philip T. , Stockbridge Norman , Strnadova Colette ,   the Cardiac Safety Research Consortium
Published: April 2018

AbstractMultiple marketing withdrawals due to proarrhythmic concerns occurred in the United States, Canada, and the United Kingdom in the late 1980s to early 2000s. This primer reviews the clinical implications of a drug's identified proarrhythmic liability, the issues associated with these safety‐related withdrawals, and the actions taken by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and by regulatory agencies in terms of changing drug development practices and introducing new nonclinical and clinical tests to asses proarrhythmic liability. ICH Guidelines S7B and E14 were released in 2005. Since then, they have been adopted by many regional regulatory authorities and have guided nonclinical and clinical proarrhythmic cardiac safety assessments during drug development. While this regulatory paradigm has been successful in preventing drugs with unanticipated potential for inducing the rare but potentially fatal polymorphic ventricular arrhythmia torsade de pointes from entering the market, it has led to the termination of drug development programs for other potentially useful medicines because of isolated results from studies with limited predictive value. Research efforts are now exploring alternative approaches to better predict potential proarrhythmic liabilities. For example, in the domain of human electrocardiographic assessments, concentration‐response modeling conducted during phase 1 clinical development has recently become an accepted alternate primary methodology to the ICH E14 “thorough QT/QTc” study for defining a drug's corrected QT interval prolongation liability under certain conditions. When a drug's therapeutic benefit is considered important at a public health level but there is also an identified proarrhythmic liability that may result from administration of the single drug in certain individuals and/or drug‐drug interactions, marketing approval will be accompanied by appropriate directions in the drug's prescribing information. Health‐care professionals in the fields of medicine and pharmacy need to consider the prescribing information in conjunction with individual patients’ clinical characteristics and concomitant medications when prescribing and dispensing such drugs.
The effects of nasal closure on quality of life in patients with hereditary hemorrhagic telangiectasia
Authors: Thomson Rhett S. , Molin Nicole L. , Whitehead Kevin J. , Ashby Shaelene , Johnson Leland , Ward P. Daniel , McRae Bryan R. , Wilson Kevin F. , McDonald Jamie 
Published: April 2018

IntroductionEpistaxis is the most common symptom of hereditary hemorrhagic telangiectasia (HHT). Complete nasal closure is one of the treatment options for patients with severe, intractable epistaxis. In our experience, this surgery can be life changing in a positive sense; but many patients as well as their physicians understandably fear that such a procedure will diminish certain aspects of quality of life (QOL).MethodsCase‐control study of HHT patients treated at the University of Utah HHT Center of Excellence with and without nasal closure from January 2005 to January 2016. Patients were matched according to epistaxis severity. Each included patient was issued three surveys: Epistaxis Severity Score (ESS), the Pittsburg Sleep Quality Index (PSQI), and the Nasal Obstruction Symptom Evaluation (NOSE).ResultsAfter treatment, the mean PSQI and NOSE scores were not significantly different between the two groups. However, the mean ESS score in the nasal closure group was significantly lower at 1.10 compared to the severe epistaxis group with a mean score of 3.99 (P = .027).ConclusionThe results of this study demonstrate that nasal closure significantly improves epistaxis severity without having a significant effect on sleep or nasal obstruction as they relate to QOL. These findings suggest that nasal closure should be considered for HHT patients with chronic severe epistaxis.Level of Evidence4.
The expression of the cancer testis antigen MAGE A4: A favorable prognostic biomarker in salivary gland carcinomas related to low tumor grading
Authors: Vital Domenic , Ikenberg Kristian , Moch Holger , Roessle Matthias , Huber Gerhard F. 
Published: April 2018

BackgroundAim was to analyze the expression of different cancer testis antigens (CTA) and to assess its prognostic value in salivary gland carcinomas.MethodsPatients with salivary gland carcinomas diagnosed 1994 to 2010 were included. Baseline characteristics, pathohistological, clinical, and outcome data were assessed. Tissue microarrays were constructed and immunohistochemistry for different CTA (NY‐ESO1, NY‐BR1, MAGE A1, MAGE A3, MAGE A4, MAGE C1/CT7, and MAGE C2/CT10) was performed. CTA expression was assessed and statistically correlated with pathological and outcome data.ResultsExpression rates of CTA in salivary gland tumors ranged from 0% to 40%. MAGE A4 expression was associated with a lower tumor grade tumor grading (P = .017), and a favorable recurrence‐free (P = .003), disease‐specific (P = .046) and overall survival (P = .028).ConclusionsMAGE A4 is a highly significant prognostic marker in salivary gland carcinoma; its expression is associated with low‐grade histology, a low rate of distant metastasis and a favorable survival.Level of Evidence4
TMTC2 variant associated with sensorineural hearing loss and auditory neuropathy spectrum disorder in a family dyad
Authors: Guillen‐Ahlers Hector , Erbe Christy B. , Chevalier Frédéric D. , Montoya Maria J. , Zimmerman Kip D. , Langefeld Carl D. , Olivier Michael , Runge Christina L. 
Published: April 2018

AbstractBackgroundSensorineural hearing loss (SNHL) is a common form of hearing loss that can be inherited or triggered by environmental insults; auditory neuropathy spectrum disorder (ANSD) is a SNHL subtype with unique diagnostic criteria. The genetic factors associated with these impairments are vast and diverse, but causal genetic factors are rarely characterized.MethodsA family dyad, both cochlear implant recipients, presented with a hearing history of bilateral, progressive SNHL, and ANSD. Whole‐exome sequencing was performed to identify coding sequence variants shared by both family members, and screened against genes relevant to hearing loss and variants known to be associated with SNHL and ANSD.ResultsBoth family members are successful cochlear implant users, demonstrating effective auditory nerve stimulation with their devices. Genetic analyses revealed a mutation (rs35725509) in the TMTC2 gene, which has been reported previously as a likely genetic cause of SNHL in another family of Northern European descent.ConclusionThis study represents the first confirmation of the rs35725509 variant in an independent family as a likely cause for the complex hearing loss phenotype (SNHL and ANSD) observed in this family dyad.
Technical Note: On maximizing Cherenkov emissions from medical linear accelerators
Authors: Shrock Zachary , Yoon Suk W. , Gunasingha Rathnayaka , Oldham Mark , Adamson Justus 
Published: April 2018

PurposeCherenkov light during MV radiotherapy has recently found imaging and therapeutic applications but is challenged by relatively low fluence. Our purpose is to investigate the feasibility of increasing Cherenkov light production during MV radiotherapy by increasing photon energy and applying specialized beam‐hardening filtration.MethodsGAMOS 5.0.0, a GEANT4‐based framework for Monte Carlo simulations, was used to model standard clinical linear accelerator primary photon beams. The photon source was incident upon a 17.8 cm3 cubic water phantom with a 94 cm source to surface distance. Dose and Cherenkov production was determined at depths of 3–9 cm. Filtration was simulated 15 cm below the photon beam source. Filter materials included aluminum, iron, and copper with thicknesses of 2–20 cm. Histories used depended on the level of attenuation from the filter, ranging from 100 million to 2 billion. Comparing average dose per history also allowed for evaluation of dose‐rate reduction for different filters.ResultsOverall, increasing photon beam energy is more effective at improving Cherenkov production per unit dose than is filtration, with a standard 18 MV beam yielding 3.3–4.0× more photons than 6 MV. Introducing an aluminum filter into an unfiltered 2400 cGy/min 10 MV beam increases the Cherenkov production by 1.6–1.7×, while maintaining a clinical dose rate of 300 cGy/min, compared to increases of ~1.5× for iron and copper. Aluminum was also more effective than the standard flattening filter, with the increase over the unfiltered beam being 1.4–1.5× (maintaining 600 cGy/min dose rate) vs 1.3–1.4× for the standard flattening filter. Applying a 10 cm aluminum filter to a standard 18 MV, photon beam increased the Cherenkov production per unit dose to 3.9–4.3× beyond that of 6 MV (vs 3.3–4.0× for 18 MV with no aluminum filter).ConclusionsThrough a combination of increasing photon energy and applying specialized beam‐hardening filtration, the amount of Cherenkov photons per unit radiotherapy dose can be increased substantially.
A joint space‐angle regularization approach for single 4D diffusion image super‐resolution
Authors: Yin Shi , You Xinge , Yang Xin , Peng Qinmu , Zhu Ziqi , Jing Xiao‐Yuan 
Published: April 2018

PurposeLow signal‐to‐noise‐ratio and limited scan time of diffusion magnetic resonance imaging (dMRI) in current clinical settings impede obtaining images with high spatial and angular resolution (HSAR) for a reliable fiber reconstruction with fine anatomical details. To overcome this problem, we propose a joint space‐angle regularization approach to reconstruct HSAR diffusion signals from a single 4D low resolution (LR) dMRI, which is down‐sampled in both 3D‐space and q‐space.MethodsDifferent from the existing works which combine multiple 4D LR diffusion images acquired using specific acquisition protocols, the proposed method reconstructs HSAR dMRI from only a single 4D dMRI by exploring and integrating two key priors, that is, the nonlocal self‐similarity in the spatial domain as a prior to increase spatial resolution and ridgelet approximations in the diffusion domain as another prior to increase the angular resolution of dMRI. To more effectively capture nonlocal self‐similarity in the spatial domain, a novel 3D block‐based nonlocal means filter is imposed as the 3D image space regularization term which is accurate in measuring the similarity and fast for 3D reconstruction. To reduce computational complexity, we use the L2‐norm instead of sparsity constraint on the representation coefficients.ResultsExperimental results demonstrate that the proposed method can obtain the HSAR dMRI efficiently with approximately 2% per‐voxel root‐mean‐square error between the actual and reconstructed HSAR dMRI.ConclusionThe proposed approach can effectively increase the spatial and angular resolution of the dMRI which is independent of the acquisition protocol, thus overcomes the inherent resolution limitation of imaging systems.
Nurses' experience with relatives of patients receiving end‐of‐life care in nursing homes and at home: A questionnaire‐based cross‐sectional study
Authors: Paulsen Bård , Johnsen Roar , Hadders Hans 
Published: April 2018

AbstractAimThe aim of this study was to explore any differences between nurses working in nursing home and home‐based care in their experiences regarding relatives' ability to accept the imminence of death and relatives' ability to reach agreement when deciding on behalf of patients unable to consent.DesignAn electronic questionnaire‐based cross‐sectional study.MethodAn electronically distributed survey to 884 nurses in long‐term care in Norway in May 2014. A total of 399 nurses responded (45%), of which 197 worked in nursing homes and 202 in home‐based care.ResultsNurses in home‐based care, more often than their colleagues in nursing homes, experienced that relatives had difficulties in accepting that patients were dying. Nurses who often felt insecure about whether life extension was in consistency with patients' wishes and nurses who talked most about life‐prolonging medical treatment in communication with relatives more often experienced that relatives being reluctant to accept a poor prognosis and disagreements between relatives in their role as proxy decision makers for the patient.
Intrinsic spontaneous brain activity predicts individual variability in associative memory in older adults
Authors: Zheng Zhiwei , Li Rui , Xiao Fengqiu , He Rongqiao , Zhang Shouzi , Li Juan 
Published: April 2018

AbstractOlder adults demonstrate notable individual differences in associative memory. Here, resting‐state functional magnetic resonance imaging (rsfMRI) was used to investigate whether intrinsic brain activity at rest could predict individual differences in associative memory among cognitively healthy older adults. Regional amplitude of low‐frequency fluctuations (ALFF) analysis and a correlation‐based resting‐state functional connectivity (RSFC) approach were used to analyze data acquired from 102 cognitively normal elderly who completed the paired‐associative learning test (PALT) and underwent fMRI scans. Participants were divided into two groups based on the retrospective self‐reports on whether or not they utilized encoding strategies during the PALT. The behavioral results revealed better associative memory performance in the participants who reported utilizing memory strategies compared with participants who reported not doing so. The fMRI results showed that higher associative memory performance was associated with greater functional connectivity between the right superior frontal gyrus and the right posterior cerebellum lobe in the strategy group. The regional ALFF values in the right superior frontal gyrus were linked to associative memory performance in the no‐strategy group. These findings suggest that the regional spontaneous fluctuations and functional connectivity during rest may subserve the individual differences in the associative memory in older adults, and that this is modulated by self‐initiated memory strategy use.