bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic review and network meta-analysis of resective surgery for mesial temporal lobe epilepsy
Authors: Jain Puneet , Tomlinson George , Snead Carter , Sander Beate , Widjaja Elysa 
Published: May 2018

ObjectiveTo evaluate the effectiveness of anterior temporal lobectomy (ATL) versus selective amygdalohippocampectomy (SAH) on seizure-free outcome in patients with temporal lobe epilepsy, using both direct and indirect evidence from the literature.MethodsMEDLINE, Embase and Cochrane databases were searched for original research articles and systematic reviews comparing ATL versus SAH, and ATL or SAH versus medical management (MM). The outcome was seizure freedom at 12 months of follow-up or longer. Direct pairwise meta-analyses were conducted, followed by a random-effect Bayesian network meta-analysis (NMA) combining direct and indirect evidence.ResultsTwenty-eight articles were included (18 compared ATL vs SAH, 1 compared ATL vs SAH vs MM, 8 compared ATL vs MM, and 1 compared SAH vs MM). Direct pairwise meta-analyses showed no significant differences in seizure-free outcome of ATL versus SAH (OR 1.14, 95% CI 0.93 to 1.39; p=0.201), but the odds of seizure-free outcome were higher for ATL versus MM (OR 29.16, 95% CI 10.44 to 81.50; p<0.00001), and SAH versus MM (OR 28.42, 95% CI 10.17 to 79.39; p<0.00001). NMA also showed that the odds of seizure-free outcome were no different in ATL versus SAH (OR 1.15, 95% credible interval (CrI) 0.84–1.15), but higher for ATL versus MM (OR 27.22, 95% CrI 15.38–27.22), and SAH versus MM (OR 23.57, 95% CrI 12.67–23.57). There were no significant differences between direct and indirect comparisons (all p>0.05).ConclusionDirect evidence, indirect evidence and NMA did not identify a difference in seizure-free outcome of ATL versus SAH.
Playing the Melanoma Endgame
Authors: Teh Jessica L.F. , Aplin Andrew E. 
Published: May 2018

Abstract
Treatments for melanoma are of two main types: targeted therapies and immune checkpoint inhibitors. However, both are effective in only a subset of patients and are limited by acquired resistance. Here, the authors present the preclinical basis to broadly target different forms of therapy-resistant melanoma. Clin Cancer Res; 24(19); 4629–30. ©2018 AACR.
See related article by Zhang et al., p. 4771
Orally Bioavailable and Blood–Brain Barrier-Penetrating ATM Inhibitor (AZ32) Radiosensitizes Intracranial Gliomas in Mice
Authors: Karlin Jeremy , Allen Jasmine , Ahmad Syed F. , Hughes Gareth , Sheridan Victoria , Odedra Rajesh , Farrington Paul , Cadogan Elaine B. , Riches Lucy C. , Garcia-Trinidad Antonio , Thomason Andrew G. , Patel Bhavika , Vincent Jennifer , Lau Alan , Pike Kurt G. , Hunt Thomas A. , Sule Amrita , Valerie Nicholas C.K. , Biddlestone-Thorpe Laura , Kahn Jenna , Beckta Jason M. , Mukhopadhyay Nitai , Barlaam Bernard , Degorce Sebastien L. , Kettle Jason , Colclough Nicola , Wilson Joanne , Smith Aaron , Barrett Ian P. , Zheng Li , Zhang Tianwei , Wang Yingchun , Chen Kan , Pass Martin , Durant Stephen T. , Valerie Kristoffer 
Published: May 2018

Abstract
Inhibition of ataxia-telangiectasia mutated (ATM) during radiotherapy of glioblastoma multiforme (GBM) may improve tumor control by short-circuiting the response to radiation-induced DNA damage. A major impediment for clinical implementation is that current inhibitors have limited central nervous system (CNS) bioavailability; thus, the goal was to identify ATM inhibitors (ATMi) with improved CNS penetration. Drug screens and refinement of lead compounds identified AZ31 and AZ32. The compounds were then tested in vivo for efficacy and impact on tumor and healthy brain. Both AZ31 and AZ32 blocked the DNA damage response and radiosensitized GBM cells in vitro. AZ32, with enhanced blood–brain barrier (BBB) penetration, was highly efficient in vivo as radiosensitizer in syngeneic and human, orthotopic mouse glioma model compared with AZ31. Furthermore, human glioma cell lines expressing mutant p53 or having checkpoint-defective mutations were particularly sensitive to ATMi radiosensitization. The mechanism for this p53 effect involves a propensity to undergo mitotic catastrophe relative to cells with wild-type p53. In vivo, apoptosis was &gt;6-fold higher in tumor relative to healthy brain after exposure to AZ32 and low-dose radiation. AZ32 is the first ATMi with oral bioavailability shown to radiosensitize glioma and improve survival in orthotopic mouse models. These findings support the development of a clinical-grade, BBB-penetrating ATMi for the treatment of GBM. Importantly, because many GBMs have defective p53 signaling, the use of an ATMi concurrent with standard radiotherapy is expected to be cancer-specific, increase the therapeutic ratio, and maintain full therapeutic effect at lower radiation doses. Mol Cancer Ther; 17(8); 1637–47. ©2018 AACR.
Right Ventricular Dysfunction and Long-Term Risk of Sudden Cardiac Death in Patients With and Without Severe Left Ventricular Dysfunction
Authors: Naksuk Niyada , Tan Nicholas , Padmanabhan Deepak , Kancharla Krishna , Makkar Nayani , Yogeswaran Vidhushei , Gaba Prakriti , Kaginele Pranita , Riley David C. , Sugrue Alan M. , Rosenbaum Andrew N. , El-Harasis Majd A. , Asirvatham Samuel J. , Kapa Suraj , McLeod Christopher J. 
Published: May 2018

Background:
Right ventricular systolic dysfunction (RVD) often coexists with various cardiopulmonary diseases. However, the association between RVD and risk of sudden cardiac death (SCD) has not been well studied. This study examined the risk of SCD associated with RVD in patients with heterogeneous underlying cardiac diseases.

Methods:
The Mayo Clinic cardiac care unit database included 5463 consecutive patients with complete echocardiographic evaluation to assess right ventricular systolic function and RVD severity. Prospective surveillance follow-up was obtained for all patients. SCD was adjudicated when a malignant ventricular arrhythmia was documented as the primary rhythm leading to death.

RESULTS:

The prevalence of mild RVD and moderate-severe RVD was 14.9% and 17.1%, respectively. Patients with RVD were more likely to have a history of congestive heart failure, cardiac arrest, pulmonary disease, and lower baseline left ventricular ejection fraction compared with those with normal right ventricular systolic function. During a median follow-up of 14 months, the incidence of SCD was highest in patients with moderate-severe RVD (7.4% versus 4.4% in mild RVD versus 1.6% in normal right ventricular function;
P
<0.001). After adjustment for baseline characteristics, mild RVD (adjusted hazard ratio, 1.57;
P
=0.046) and moderate-severe RVD (adjusted hazard ratio, 1.91;
P
=0.006) were independently associated with an increased risk of SCD. Moderate-severe RVD remained an independent predictor of SCD for patients with left ventricular ejection fraction >35% without or with preexisting implantable cardioverter-defibrillator (adjusted hazard ratio, 4.12;
P
=0.003 and adjusted hazard ratio, 5.04;
P
<0.001, respectively).

Conclusions:
Presence of RVD in patients with a history of preexisting cardiac disease is an independent predictor of SCD irrespective of left ventricular ejection fraction.
Baby M Turns 30: The Law and Policy of Surrogate Motherhood
Authors: Feldman Eric A. 
Published: May 2018

This article marks the 30th anniversary of the Supreme Court of New Jersey's Baby M decision by offering a critical analysis of surrogacy policy in the United States. Despite fundamental changes in both science and society since the case was decided, state courts and legislatures remain bitterly divided on the legality of surrogacy. In arguing for a more uniform, permissive legal posture toward surrogacy, the article addresses five central debates in the surrogacy literature.First, should the legal system accommodate those seeking conception through surrogacy, or should it prohibit such arrangements? Second, if surrogacy is permitted, what steps can be taken to minimize the potential exploitation of women who are willing to rent their wombs for income? Third, what criteria should govern the eligibility to serve as a surrogate mother and an intended parent? Fourth, what principle(s) should serve as the basis for determining the parentage of children born through surrogacy? Fifth, is regulatory uniformity in the surrogacy realm desirable? Is it achievable?The article concludes that courts and legislatures should accept the validity of surrogacy contracts, determine parentage according to intent, and identify transparent criteria for the eligibility of both surrogates and intended parents.
Swaps and Chains and Vouchers, Oh My!: Evaluating How Saving More Lives Impacts the Equitable Allocation of Live Donor Kidneys
Authors: Tenenbaum Evelyn M. 
Published: May 2018

Live kidney donation involves a delicate balance between saving the most lives possible and maintaining a transplant system that is fair to the many thousands of patients on the transplant waiting list. Federal law and regulations require that kidney allocation be equitable, but the pressure to save patients subject to ever-lengthening waiting times for a transplant has been swinging the balance toward optimizing utility at the expense of justice.This article traces the progression of innovations created to make optimum use of a patient's own live donors. It starts with the simplest – direct donation by family members – and ends with voucher donations, a very recent and unique innovation because the donor can donate 20 or more years before the intended recipient is expected to need a kidney. In return for the donation, the intended recipient receives a voucher that can be redeemed for a live kidney when it is needed. Other innovations that are discussed include kidney exchanges and list paired donation, which are used to facilitate donor swaps when donor/recipient pairs have incompatible blood types.The discussion of each new innovation shows how the equity issues build on each other and how, with each new innovation, it becomes progressively harder to find an acceptable balance between utility and justice. The article culminates with an analysis of two recent allocation methods that have the potential to save many additional lives, but also affirmatively harm some patients on the deceased donor waiting list by increasing their waiting time for a life-saving kidney. The article concludes that saving additional lives does not justify harming patients on the waiting list unless that harm can be minimized. It also proposes solutions to minimize the harm so these new innovations can equitably perform their intended function of stimulating additional transplants and extending the lives of many transplant patients.
External beam radiotherapy for the treatment of feline salivary gland carcinoma: six new cases and a review of the literature
Authors: Blackwood Laura , Harper Aaron , Elliott James , Gramer Irina 
Published: May 2018

Case series summary Salivary gland carcinoma is uncommon in cats. We report the outcome of radiation therapy in six cases (four salivary gland adenocarcinomas, one tubulopapillary adenocarcinoma, one carcinoma). Five were treated after surgical excision of the primary tumour, but four had gross disease (primary or metastatic) at the time of starting radiotherapy. Exact progression-free interval from the start of radiotherapy in the two cats where this was known was 120 and 144 days, respectively. One cat was signed off at 766 days with no evidence of recurrence. Another cat was in remission at 202 days (when last seen by the referring practice) but subsequently developed recurrence (date uncertain). Survival time was known for three cats (55 days, 258 days and 570 days from initiation of radiotherapy, respectively). In two cases, locoregional progressive disease (PD) was confirmed, and the other presumed as the cause of death. Two cats, known to have developed PD, were alive at the time of writing (at 206 and 549 days, respectively). No cat died as a result of distant metastatic disease. Relevance and novel information There is a paucity of information on the treatment of salivary gland tumours. In humans, as in cats, there is no optimised standard of care for malignant tumours. It is accepted that, for surgical candidates (even with large tumours), surgery and radiotherapy is superior to radiotherapy alone. However, the benefits of postoperative radiotherapy compared with surgery alone are only clear in patients with high-risk tumours (ie, those with large and invasive primary tumours, close or incomplete margins, high histopathological grade, histological evidence of neural or vascular invasion, or positive lymph nodes). This population is analogous to the population reported here, and likely to most cats presented in practice. Thus, radiation therapy may help improve locoregional control and survival in cats.
Bim regulates the survival and suppressive capability of CD8+ FOXP3+ regulatory T cells during murine GVHD
Authors: Agle Kimberle , Vincent Benjamin G. , Piper Clint , Belle Ludovic , Zhou Vivian , Shlomchik Warren , Serody Jonathan S. , Drobyski William R. 
Published: May 2018

Key PointsCD8+ Tregs possess a proapoptotic phenotype when compared with CD4+ Tregs, which is characterized by an inversion of the Bim/Mcl-1 ratio. Absence of Bim in adoptively transferred CD8+ Tregs results in augmented in vivo survival and superior protection from GVHD.
A gene signature that distinguishes conventional and leukemic nonnodal mantle cell lymphoma helps predict outcome
Authors: Clot Guillem , Jares Pedro , Giné Eva , Navarro Alba , Royo Cristina , Pinyol Magda , Martín-Garcia David , Demajo Santiago , Espinet Blanca , Salar Antonio , Ferrer Ana , Muntañola Ana , Aymerich Marta , Rauert-Wunderlich Hilka , Jaffe Elaine S. , Connors Joseph M. , Gascoyne Randy D. , Delabie Jan , López-Guillermo Armando , Ott German , Wright George W. , Staudt Louis M. , Rosenwald Andreas , Scott David W. , Rimsza Lisa M. , Beà Sílvia , Campo Elías 
Published: May 2018

Key PointsA new molecular assay identifies conventional and leukemic nonnodal MCL with differing clinicobiological features. The integration of the novel assay with genetic alterations identifies subsets of MCL patients with different management and outcome.
Pulmonary function tests as outcomes for systemic sclerosis interstitial lung disease
Authors: Caron Melissa , Hoa Sabrina , Hudson Marie , Schwartzman Kevin , Steele Russell 
Published: May 2018

Interstitial lung disease (ILD) is the leading cause of morbidity and mortality in systemic sclerosis (SSc). We performed a systematic review to characterise the use and validation of pulmonary function tests (PFTs) as surrogate markers for systemic sclerosis-associated interstitial lung disease (SSc-ILD) progression.Five electronic databases were searched to identify all relevant studies. Included studies either used at least one PFT measure as a longitudinal outcome for SSc-ILD progression (i.e.outcome studies) and/or reported at least one classical measure of validity for the PFTs in SSc-ILD (i.e.validation studies).This systematic review included 169 outcome studies and 50 validation studies. Diffusing capacity of the lung for carbon monoxide (DLCO) was cumulatively the most commonly used outcome until 2010 when it was surpassed by forced vital capacity (FVC). FVC (% predicted) was the primary endpoint in 70.4% of studies, compared to 11.3% for % predictedDLCO. Only five studies specifically aimed to validate the PFTs: two concluded thatDLCOwas the best measure of SSc-ILD extent, while the others did not favour any PFT. These studies also showed respectable validity measures for total lung capacity (TLC).Despite the current preference for FVC, available evidence suggests thatDLCOand TLC should not yet be discounted as potential surrogate markers for SSc-ILD progression.
How long is enough? Identification of product dry-time as a primary driver of alcohol-based hand rub efficacy
Authors: Suchomel Miranda , Leslie Rachel A. , Parker Albert E. , Macinga David R. 
Published: May 2018

Abstract
Background
The World Health Organization has called for the development of improved methodologies to evaluate alcohol-based handrub (ABHR) efficacy, including evaluation at “short application times and volumes that reflect actual use in healthcare facilities”. The objective of this study was to investigate variables influencing ABHR efficacy, under test conditions reflective of clinical use.

Methods
The test product (60% V/V 2-propanol) was evaluated according to a modified EN 1500 methodology, where application volumes of 1 mL, 2 mL, and 3 mL were rubbed until dry. Statistical analyses were performed to investigate the relative influences of product volume, hand size, and product dry-time on efficacy, and hand size and hand contamination on product dry-time.

Results
Mean log10 reduction factors (SD) were 1.99 (0.66), 2.96 (0.84) and 3.28 (0.96); and mean dry-times (SD) were 24 s (7 s), 50 s (14 s), and 67 s (20 s) at application volumes of 1 mL, 2 mL, and 3 mL, respectively (p ≤ 0.030). When data were examined at the individual volunteer level, there was a statistically significant correlation between dry-time and log reduction factor (p < 0.0001), independent of application volume. There was also a statistically significant correlation between hand surface area and dry-times (p = 0.047), but no correlation between hand surface area and efficacy (p = 0.698).

Conclusions
When keeping other variables such as alcohol type and concentration constant, product dry-time appears to be the primary driver of ABHR efficacy suggesting that dosing should be customized to each individual and focus on achieving a product dry-time delivering adequate efficacy.
Consumer responses to company disclosure of socially responsible efforts
Authors: Lee Hyun-Hwa , Lee Minsun , Ma Yoon Jin 
Published: May 2018

AbstractSince the California Transparency in Supply Chains Act (CTSCA) was enacted, many large apparel retailers are required to post a corporate social responsibility statement on their website regarding their practices. The present study applies the CTSCA to the shopping context for evaluating consumer responses. A factorial experimental study using a scenario method was designed to explore the aims of this study. Participants were randomly assigned to one of two scenarios regarding either an apparel company’s website being compliant with the CTSCA, or an apparel company not have a disclosure on its website and therefore in violation of the CTSCA. A total of 716 responses were used in data analysis. The results show that there were significant effects of the presence of CTSCA on retailers’ website on consumer responses, after controlling consumer characteristics of socially responsible consumption behavior. That is, respondents in the study perceived that presenting the public statement in compliance with the CTSCA on a company’s website was more persuasive in decision making, promoted trust and enhanced usage and purchase intentions. The findings of the study suggest academic and marketing implications.
Treatment-resistant depression and peripheral C-reactive protein
Authors: Chamberlain Samuel R. , Cavanagh Jonathan , de Boer Peter , Mondelli Valeria , Jones Declan N.C. , Drevets Wayne C. , Cowen Philip J. , Harrison Neil A. , Pointon Linda , Pariante Carmine M. , Bullmore Edward T. 
Published: May 2018

BackgroundC-reactive protein (CRP) is a candidate biomarker for major depressive disorder (MDD), but it is unclear how peripheral CRP levels relate to the heterogeneous clinical phenotypes of the disorder.AimTo explore CRP in MDD and its phenotypic associations.MethodWe recruited 102 treatment-resistant patients with MDD currently experiencing depression, 48 treatment-responsive patients with MDD not currently experiencing depression, 48 patients with depression who were not receiving medication and 54 healthy volunteers. High-sensitivity CRP in peripheral venous blood, body mass index (BMI) and questionnaire assessments of depression, anxiety and childhood trauma were measured. Group differences in CRP were estimated, and partial least squares (PLS) analysis explored the relationships between CRP and specific clinical phenotypes.ResultsCompared with healthy volunteers, BMI-corrected CRP was significantly elevated in the treatment-resistant group (P = 0.007; Cohen's d = 0.47); but not significantly so in the treatment-responsive (d = 0.29) and untreated (d = 0.18) groups. PLS yielded an optimal two-factor solution that accounted for 34.7% of variation in clinical measures and for 36.0% of variation in CRP. Clinical phenotypes most strongly associated with CRP and heavily weighted on the first PLS component were vegetative depressive symptoms, BMI, state anxiety and feeling unloved as a child or wishing for a different childhood.ConclusionsCRP was elevated in patients with MDD, and more so in treatment-resistant patients. Other phenotypes associated with elevated CRP included childhood adversity and specific depressive and anxious symptoms. We suggest that patients with MDD stratified for proinflammatory biomarkers, like CRP, have a distinctive clinical profile that might be responsive to second-line treatment with anti-inflammatory drugs.Declaration of interestS.R.C. consults for Cambridge Cognition and Shire; and his input in this project was funded by a Wellcome Trust Clinical Fellowship (110049/Z/15/Z). E.T.B. is employed half time by the University of Cambridge and half time by GlaxoSmithKline; he holds stock in GlaxoSmithKline. In the past 3 years, P.J.C. has served on an advisory board for Lundbeck. N.A.H. consults for GlaxoSmithKline. P.d.B., D.N.C.J. and W.C.D. are employees of Janssen Research & Development, LLC., of Johnson & Johnson, and hold stock in Johnson & Johnson. The other authors report no financial disclosures or potential conflicts of interest.
Final Overall Survival Analysis From a Study Comparing First-Line Crizotinib Versus Chemotherapy in ALK-Mutation-Positive Non–Small-Cell Lung Cancer
Authors: Solomon Benjamin J. , Kim Dong-Wan , Wu Yi-Long , Nakagawa Kazuhiko , Mekhail Tarek , Felip Enriqueta , Cappuzzo Federico , Paolini Jolanda , Usari Tiziana , Tang Yiyun , Wilner Keith D. , Blackhall Fiona , Mok Tony S. 
Published: May 2018

Purpose The phase III PROFILE 1014 trial compared crizotinib with chemotherapy as first-line treatment in patients with anaplastic lymphoma kinase (ALK) –positive advanced nonsquamous non–small-cell lung cancer. Here, we report the final overall survival (OS) results. Patients and Methods Patients were randomly assigned to receive oral crizotinib 250 mg twice daily (n = 172) or intravenous pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 or carboplatin (area under the concentration–time curve of 5 to 6 mg·mL/min) every 3 weeks for a maximum of six cycles (n = 171). Crossover to crizotinib was permitted after disease progression. OS was analyzed using a stratified log-rank test and a prespecified rank-preserving structural failure time model to account for crossover. Results Median follow-up duration for OS was approximately 46 months for both arms. In the chemotherapy arm, 144 patients (84.2%) received crizotinib in subsequent lines. Hazard ratio for OS was 0.760 (95% CI, 0.548 to 1.053; two-sided P = .0978). Median OS was not reached (NR) with crizotinib (95% CI, 45.8 months to NR) and 47.5 months with chemotherapy (95% CI, 32.2 months to NR). Survival probability at 4 years was 56.6% (95% CI, 48.3% to 64.1%) with crizotinib and 49.1% (95% CI, 40.5% to 57.1%) with chemotherapy. After crossover adjustment, there was an improvement in OS that favored crizotinib (hazard ratio, 0.346; 95% bootstrap CI, 0.081 to 0.718). The longest OS was observed in crizotinib-treated patients who received a subsequent ALK tyrosine kinase inhibitor. No new safety signals were identified. Conclusion The final analysis of the PROFILE 1014 study provides a new benchmark for OS in patients with ALK-rearranged non–small-cell lung cancer and highlights the benefit of crizotinib for prolonging survival in this patient population.