bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurocognitive and mental health outcomes and association with quality of life among adults living with HIV: a cross-sectional focus on a low-literacy population from coastal Kenya
Authors: Nyongesa Moses Kachama , Mwangala Patrick N , Mwangi Paul , Kombe Martha , Newton Charles R J C , Abubakar Amina A 
Published: September 2018

ObjectivesOur aim was to compare the neurocognitive performance and mental health outcome of adults living with HIV on antiretroviral therapy with that of community controls, all of low literacy. Furthermore, we also wanted to explore the relationship of these outcomes with quality of life among adults living with HIV.Study designThis was a descriptive cross-sectional study.SettingThe study was conducted in Kilifi County, a region located at the Kenyan coast.ParticipantsThe participants consisted of a consecutive sample of 84 adults living with HIV and 83 randomly selected community controls all with ≤8 years of schooling. All participants were assessed for non-verbal intelligence, verbal working memory and executive functioning. The Major Depression Inventory and a quality of life measure (RAND SF-36) were also administered.ResultsUsing analysis of covariance, we found no statistically significant group differences between adults living with HIV and community controls in all the neurocognitive tests except for a marginal difference in the non-verbal intelligence test (F (1, 158)=3.83, p=0.05). However, depressive scores of adults living with HIV were significantly higher than those of controls (F (1, 158)=11.56, p<0.01). Also, quality of life scores of adults living with HIV were significantly lower than those of controls (F (1, 158)=4.62, p=0.03). For the HIV-infected group, results from multivariable linear regression analysis showed that increasing depressive scores were significantly associated with poorer quality of life (β=−1.17, 95% CI −1.55 to –0.80; p<0.01).ConclusionOur findings suggest that adults of low-literacy levels living with HIV and on antiretroviral medication at the Kenyan coast do not have significant cognitive deficits compared with their uninfected counterparts. However, their mental health, compared with that of HIV-uninfected adults, remains poorer and their quality of life may deteriorate when HIV and depressive symptoms co-occur.
Atrial fibrillation detection using single lead portable electrocardiographic monitoring: a systematic review and meta-analysis
Authors: Ramkumar Satish , Nerlekar Nitesh , D’Souza Daniel , Pol Derek J , Kalman Jonathan M , Marwick Thomas H 
Published: September 2018

ObjectivesRecent technology advances have allowed for heart rhythm monitoring using single-lead ECG monitoring devices, which can be used for early diagnosis of atrial fibrillation (AF). We sought to investigate the AF detection rate using portable ECG devices compared with Holter monitoring.Setting, participants and outcome measuresWe searched the Medline, Embase and Scopus databases (conducted on 8 May 2017) using search terms related to AF screening and included studies with adults aged >18 years using portable ECG devices or Holter monitoring for AF detection. We excluded studies using implantable loop recorders and pacemakers. Using a random-effects model we calculated the overall AF detection rate. Meta-regression analysis was performed to explore potential sources for heterogeneity. Quality of reporting was assessed using the tool developed by Downs and Black.ResultsPortable ECG monitoring was used in 18 studies (n=117 436) and Holter monitoring was used in 36 studies (n=8498). The AF detection rate using portable ECG monitoring was 1.7% (95% CI 1.4 to 2.1), with significant heterogeneity between studies (p<0.001). There was a moderate linear relationship between total monitoring time and AF detection rate (r=0.65, p=0.003), and meta-regression identified total monitoring time (p=0.005) and body mass index (p=0.01) as potential contributors to heterogeneity. The detection rate (4.8%, 95% CI 3.6% to 6.0%) in eight studies (n=10 199), which performed multiple ECG recordings was comparable to that with 24 hours Holter (4.6%, 95% CI 3.5% to 5.7%). Intermittent recordings for 19 min total produced similar AF detection to 24 hours Holter monitoring.ConclusionPortable ECG devices may offer an efficient screening option for AF compared with 24 hours Holter monitoring.PROSPERO registration numberCRD42017061021.
What can patients tell us about the quality and safety of hospital care? Findings from a UK multicentre survey study
Authors: O’Hara Jane K , Reynolds Caroline , Moore Sally , Armitage Gerry , Sheard Laura , Marsh Claire , Watt Ian , Wright John , Lawton Rebecca 
Published: September 2018

BackgroundPatient safety measurement remains a global challenge. Patients are an important but neglected source of learning; however, little is known about what patients can add to our understanding of safety. We sought to understand the incidence and nature of patient-reported safety concerns in hospital.MethodsFeedback about the experience of safety within hospital was gathered from 2471 inpatients as part of a multicentre, waitlist cluster randomised controlled trial of an intervention, undertaken within 33 wards across three English NHS Trusts, between May 2013 and September 2014. Patient volunteers, supported by researchers, developed a classification framework of patient-reported safety concerns from a random sample of 231 reports. All reports were then classified using the patient-developed categories. Following this, all patient-reported safety concerns underwent a two-stage clinical review process for identification of patient safety incidents.ResultsOf the 2471 inpatients recruited, 579 provided 1155 patient-reported incident reports. 14 categories were developed for classification of reports, with communication the most frequently occurring (22%), followed by staffing issues (13%) and problems with the care environment (12%). 406 of the total 1155 patient incident reports (35%) were classified by clinicians as a patient safety incident according to the standard definition. 1 in 10 patients (264 patients) identified a patient safety incident, with medication errors the most frequently reported incident.ConclusionsOur findings suggest that patients can provide insight about safety that complements existing patient safety measurement, with a frequency of reported patient safety incidents that is similar to those obtained via case note review. However, patients provide a unique perspective about hospital safety which differs from and adds to current definitions of patient safety incidents.Trial registration numberISRCTN07689702; pre-results.
Implementing bedside rounds to improve patient-centred outcomes: a systematic review
Authors: Ratelle John T , Sawatsky Adam P , Kashiwagi Deanne T , Schouten Will M , Erwin Patricia J , Gonzalo Jed D , Beckman Thomas J , West Colin P 
Published: September 2018

BackgroundBedside rounds (BR) have been proposed as an ideal method to promote patient-centred hospital care, but there is substantial variation in their implementation and effects. Our objectives were to describe the implementation of BR in hospital settings and determine their effect on patient-centred outcomes.MethodsData sources included Ovid MEDLINE, Ovid Embase, Scopus and Ovid Cochrane Central Registry of Clinical Trials from database inception through 28 July 2017. We included experimental studies comparing BR to another form of rounds in a hospital-based setting (ie, medical/surgical unit, intensive care unit (ICU)) and reporting a quantitative patient-reported or objectively measured clinical outcome. We used random effects models to calculate pooled Cohen's d effect size estimates for the patient knowledge and patient experience outcome domains.ResultsTwenty-nine studies met inclusion criteria, including 20 from adult care (17 non-ICU, 3 ICU), and nine from paediatrics (5 non-ICU, 4 ICU), the majority of which (n=23) were conducted in the USA. Thirteen studies implemented BR with cointerventions as part of a ‘bundle’. Studies most commonly reported outcomes in the domains of patient experience (n=24) and patient knowledge (n=10). We found a small, statistically significant improvement in patient experience with BR (summary Cohen’s d=0.09, 95% CI 0.04 to 0.14, p<0.001, I2=56%), but no significant association between BR and patient knowledge (Cohen’s d=0.21, 95% CI −0.004 to –0.43, p=0.054, I2=92%). Risk of bias was moderate to high, with methodological limitations most often relating to selective reporting, low adherence rates and missing data.ConclusionsBR have been implemented in a variety of hospital settings, often ‘bundled’ with cointerventions. However, BR have demonstrated limited effect on patient-centred outcomes.
A treasure chest full of nanogranitoids: an archive to investigate crustal melting in the Bohemian Massif
Authors: Ferrero Silvio , O’Brien Patrick J. , Borghini Alessia , Wunder Bernd , Wälle Markus , Günter Christina , Ziemann Martin A. 
Published: September 2018

Abstract
The central European Bohemian Massif has undergone over two centuries of scientific investigation which has made it a pivotal area for the development and testing of modern geological theories. The discovery of melt inclusions in high-grade rocks, either crystallized as nanogranitoids or as glassy inclusions, prompted the re-evaluation of the area with an ‘inclusionist’ eye. Melt inclusions have been identified in a wide range of rocks, including felsic/perpotassic granulites, migmatites, eclogites and garnet clinopyroxenites, all the result of melting events albeit over a wide range of pressure/temperature conditions (800–1000°C/0.5–5 GPa). This contribution provides an overview of such inclusions and discusses the qualitative and quantitative constraints they provide for melting processes, and the nature of melts and fluids involved in these processes. In particular, data on trace-element signatures of melt inclusions trapped at mantle depths are presented and discussed. Moreover, experimental re-homogenization of nanogranitoids provided microstructural criteria allowing assessment of the conditions at which melt and host are mutually stable during melting. Overall this work aims to provide guidelines and suggestions for petrologists wishing to explore the fascinating field of melt inclusions in metamorphic terranes worldwide, based on the newest discoveries from the still-enigmatic Bohemian Massif.
Organic geochemical research analytics of the petroleum industry: enhanced data density and method flexibility using gas chromatograph multiple detector coupling
Authors: Doerner M. , Berner U. , Erdmann M. , Barth T. 
Published: September 2018

Abstract

In traditional organic geochemical investigations analyses are usually segmented in rather time-consuming single working steps that also require off-line preparation for each analytical instrument which can add to analytical bias. Since industry laboratories need to be precise, as well as cost- and time-efficient, we present a flexible and modular analytical concept which enables the user to perform advanced organic geochemical methods on a single gas chromatograph coupled to multiple detectors. The coupled analytical system can perform analyses of natural gas composition up to
n
-butane, stable carbon isotopes of natural gas compounds up to
n
-butane, identification and quantification of major compounds in oils and extracts, and compound-specific isotopes of oil and extracts. The analytical methodologies are appropriate for enhancement to broaden the application spectrum of coupled detectors.
A Mazing 2+ε Approximation for Unsplittable Flow on a Path
Authors: Anagnostopoulos Aris , Grandoni Fabrizio , Leonardi Stefano , Wiese Andreas 
Published: September 2018

We study the problem of unsplittable flow on a path (UFP), which arises naturally in many applications such as bandwidth allocation, job scheduling, and caching. Here we are given a path with nonnegative edge capacities and a set of tasks, which are characterized by a subpath, a demand, and a profit. The goal is to find the most profitable subset of tasks whose total demand does not violate the edge capacities. Not surprisingly, this problem has received a lot of attention in the research community.

If the demand of each task is at most a small-enough fraction δ of the capacity along its subpath (δ-
small tasks
), then it has been known for a long time [Chekuri et al., ICALP 2003] how to compute a solution of value arbitrarily close to the optimum via LP rounding. However, much remains unknown for the complementary case, that is, when the demand of each task is at least some fraction δ > 0 of the smallest capacity of its subpath (δ-
large tasks
). For this setting, a constant factor approximation is known, improving on an earlier logarithmic approximation [Bonsma et al., FOCS 2011].

In this article, we present a polynomial-time approximation scheme (PTAS) for δ-large tasks, for any constant δ > 0. Key to this result is a complex geometrically inspired dynamic program. Each task is represented as a segment underneath the capacity curve, and we identify a proper maze-like structure so that each
corridor
of the maze is
crossed
by only
O
(1) tasks in the optimal solution. The maze has a tree topology, which guides our dynamic program. Our result implies a 2+ε approximation for UFP, for any constant ε > 0, improving on the previously best 7+ε approximation by Bonsma et al. We remark that our improved approximation algorithm matches the best known approximation ratio for the considerably easier special case of uniform edge capacities.
NOTCH1 Represses MCL-1 Levels in GSI-resistant T-ALL, Making them Susceptible to ABT-263
Authors: Dastur Anahita , Choi AHyun , Costa Carlotta , Yin Xunqin , Williams August , McClanaghan Joseph , Greenberg Max , Roderick Justine , Patel Neha U. , Boisvert Jessica , McDermott Ultan , Garnett Mathew J. , Almenara Jorge , Grant Steven , Rizzo Kathryn , Engelman Jeffrey A. , Kelliher Michelle , Faber Anthony C. , Benes Cyril H. 
Published: September 2018

Abstract

Purpose:
Effective targeted therapies are lacking for refractory and relapsed T-cell acute lymphoblastic leukemia (T-ALL). Suppression of the NOTCH pathway using gamma-secretase inhibitors (GSI) is toxic and clinically not effective. The goal of this study was to identify alternative therapeutic strategies for T-ALL.

Experimental Design:
We performed a comprehensive analysis of our high-throughput drug screen across hundreds of human cell lines including 15 T-ALL models. We validated and further studied the top hit, navitoclax (ABT-263). We used multiple human T-ALL cell lines as well as primary patient samples, and performed both in vitro experiments and in vivo studies on patient-derived xenograft models.

Results:
We found that T-ALL are hypersensitive to navitoclax, an inhibitor of BCL2 family of antiapoptotic proteins. Importantly, GSI-resistant T-ALL are also susceptible to navitoclax. Sensitivity to navitoclax is due to low levels of MCL-1 in T-ALL. We identify an unsuspected regulation of mTORC1 by the NOTCH pathway, resulting in increased MCL-1 upon GSI treatment. Finally, we show that pharmacologic inhibition of mTORC1 lowers MCL-1 levels and further sensitizes cells to navitoclax in vitro and leads to tumor regressions in vivo.

Conclusions:
Our results support the development of navitoclax, as single agent and in combination with mTOR inhibitors, as a new therapeutic strategy for T-ALL, including in the setting of GSI resistance.
MAVERICC, a Randomized, Biomarker-stratified, Phase II Study of mFOLFOX6-Bevacizumab versus FOLFIRI-Bevacizumab as First-line Chemotherapy in Metastatic Colorectal Cancer
Authors: Parikh Aparna R. , Lee Fa-Chyi , Yau Linda , Koh Han , Knost James , Mitchell Edith P. , Bosanac Ivan , Choong Nicholas , Scappaticci Frank , Mancao Christoph , Lenz Heinz-Josef 
Published: September 2018

Abstract

Purpose:
MAVERICC compared the efficacy and safety of modified leucovorin/5-fluorouracil/oxaliplatin plus bevacizumab (mFOLFOX6-BV) with leucovorin/5-fluorouracil/irinotecan plus bevacizumab (FOLFIRI-BV) in patients with previously untreated metastatic colorectal cancer (mCRC).
Patients and Methods: MAVERICC was a global, randomized, open-label, phase II study. Primary objectives were to assess associations between (i) excision repair cross-complementing 1 (ERCC1) expression with progression-free survival (PFS), and (ii) plasma VEGF A (VEGF-A) with PFS in patients with previously untreated mCRC receiving mFOLFOX6-BV or FOLFIRI-BV. Before randomization, patients were stratified by tumoral ERCC1/β-actin mRNA expression level and region.

Results:
Of 376 enrolled patients, 188 each received mFOLFOX6-BV and FOLFIRI-BV. PFS and overall survival (OS) were comparable between FOLFIRI-BV and mFOLFOX6-BV, with numerically higher PFS [HR = 0.79; 95% CI (confidence interval): 0.61–1.01; P = 0.06] and OS (HR = 0.76; 95% CI: 0.56–1.04; P = 0.09) observed for FOLFIRI-BV. In the high ERCC1 subgroup, PFS and OS were comparable between treatment groups (PFS, HR = 0.84; 95% CI: 0.56–1.26; P = 0.40; OS, HR = 0.80; 95% CI: 0.51–1.26; P = 0.33). Across treatment groups, high plasma VEGF-A levels (&gt;5.1 pg/mL) were observed with shorter PFS (HR = 1.19; 95% CI: 0.93–1.53; P = 0.17) and significantly shorter OS (HR = 1.64; 95% CI: 1.20–2.24; P &lt; 0.01) versus low levels (≤5.1 pg/mL). Safety findings for FOLFIRI-BV or mFOLFOX6-BV were comparable with those reported previously.

Conclusions:
First-line FOLFIRI-BV and mFOLFOX6-BV had comparable PFS and OS, similar to results in patients with high baseline tumor ERCC1 levels. There were no new safety signals with these bevacizumab-containing regimens.
A Novel Approach for Image-Guided 131I Therapy of Pancreatic Ductal Adenocarcinoma Using Mesenchymal Stem Cell-Mediated NIS Gene Delivery
Authors: Schug Christina , Gupta Aayush , Urnauer Sarah , Steiger Katja , Cheung Phyllis Fung-Yi , Neander Christian , Savvatakis Konstantinos , Schmohl Kathrin A. , Trajkovic-Arsic Marija , Schwenk Nathalie , Schwaiger Markus , Nelson Peter J. , Siveke Jens T. , Spitzweg Christine 
Published: September 2018

Abstract

The sodium iodide symporter (SLC5A5/NIS) as theranostic gene would allow for non-invasive imaging of functional NIS expression and therapeutic radioiodine application. Genetically engineered mesenchymal stem cells (MSC), based on their tumor-homing abilities, show great promise as tumor-selective NIS gene delivery vehicles for non-thyroidal tumors. As a next step towards clinical application, tumor specificity and efficacy of MSCs were investigated in an advanced genetically engineered mouse model of pancreatic ductal adenocarcinoma (PDAC). Syngeneic murine MSCs were stably transfected with a NIS-expressing plasmid driven by the CMV-promoter (NIS-MSC). In vivo 123I-scintigraphy and 124I-PET revealed significant perchlorate-sensitive NIS-mediated radioiodide accumulation in PDAC after systemic injection of NIS-MSCs. Active MSC recruitment into the tumor stroma was confirmed using NIS immunohistochemistry (IHC). A therapeutic strategy, consisting of three cycles of systemic MSC-mediated NIS delivery, followed by 131I application, resulted in a significant delay and reduction in tumor growth as compared to controls. Furthermore, IHC analysis of α-SMA and Ki67 revealed differences in the amount and behavior of activated fibroblasts in tumors of mice injected with NIS-MSCs as compared with saline-treated mice. Taken together, MSCs as NIS gene delivery vehicles in this advanced endogenous PDAC mouse model demonstrated high stromal targeting of NIS by selective recruitment of NIS-MSCs after systemic application resulting in an impressive 131I therapeutic effect.

Implications:
These data expand the prospect of MSC-mediated radioiodine imaging-guided therapy of pancreatic cancer using the sodium iodide symporter as a theranostic gene in a clinical setting.
Lung-Enriched Mutations in the p53 Tumor Suppressor: A Paradigm for Tissue-Specific Gain of Oncogenic Function
Authors: Barta Julie A. , McMahon Steven B. 
Published: September 2018

Abstract
Lung cancer, the leading cause of cancer-related mortality in the United States, occurs primarily due to prolonged exposure to an array of carcinogenic compounds in cigarette smoke. These carcinogens create bulky DNA adducts, inducing alterations including missense mutations in the tumor suppressor gene TP53. TP53 is the most commonly mutated gene in many human cancers, and a specific set of these variants are enriched in lung cancer (at amino acid residues V157, R158, and A159). This perspective postulates that lung-enriched mutations can be explained, in part, by biological selection for oncogenic gain-of-function (GOF) mutant p53 alleles at V157, R158, and A159. This hypothesis explaining tissue-specific TP53 mutations is further supported by mouse model studies of the canonical TP53 hotspots showing that tumor spectra and GOF activities are altered with mutation type. Therefore, although smoking-related lung cancer unequivocally arises due to the mutagenic environment induced by tobacco carcinogens, this perspective provides a rationale for the preferential selection of lung-enriched V157, R158, and A159 mutant p53.
Targeting the MIF/CXCR7/AKT Signaling Pathway in Castration-Resistant Prostate Cancer
Authors: Rafiei Shahrzad , Gui Bin , Wu Jiaxin , Liu X. Shirley , Kibel Adam S. , Jia Li 
Published: September 2018

Abstract

Although androgen deprivation therapy (ADT) is an effective treatment for metastatic prostate cancer, incurable castration-resistant prostate cancer (CRPC) inevitably develops. Importantly, androgen receptor (AR) continues to be critical for prostate cancer growth and progression after ADT. One of the underlying molecular mechanisms is derepression of AR-repressed genes involved in cell cycle and proliferation after ADT. Here, the data demonstrate that C-X-C chemokine receptor type 7 (CXCR7), a seven-transmembrane G-protein–coupled chemokine receptor, is an AR-repressed gene and is upregulated after ADT. AR directly regulates CXCR7 using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) gene editing. Macrophage migration inhibitory factor (MIF) was identified as a ligand for CXCR7, which induces expression of cell-cycle genes through activating AKT signaling pathway. Previous studies have been focused on chemokine CXCL12 and its receptor CXCR4 in mediating metastasis of various cancer types, including prostate cancer. The critical roles of CXCL12/CXCR4 axis in the interaction between cancer cells and their microenvironment render it a promising therapeutic target in cancer treatment. The data suggest that the MIF/CXCR7/AKT pathway drives CRPC growth and metastasis independent of the CXCL12/CXCR4 axis. Furthermore, CXCR7 blockade in combination with anti-androgen enzalutamide inhibits CRPC tumor growth and potentially prevents metastasis. Notably, both MIF and CXCR7 are overexpressed in CRPC patient specimens and therefore are attractive therapeutic targets for these patients.

Implications:
This work suggests that CXCR7 plays more important roles than CXCR4 in CRPC progression; thus, targeting CXCR7 in combination with anti-androgen is a promising therapeutic approach for metastatic CRPC.