bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gain a child, lose a tooth? Using natural experiments to distinguish between fact and fiction
Authors: Gabel Frank , Jürges Hendrik , Kruk Kai E , Listl Stefan 
Published: April 2018

BackgroundDental diseases are among the most frequent diseases globally and tooth loss imposes a substantial burden on peoples' quality of life. Non-experimental evidence suggests that individuals with more children have more missing teeth than individuals with fewer children, but until now there is no causal evidence for or against this.MethodsUsing a Two-Stage Least Squares (2SLS) instrumental variables approach and large-scale cross-sectional data from the Survey of Health, Ageing, and Retirement in Europe (study sample: 34 843 non-institutionalised individuals aged 50+ from 14 European countries and Israel; data were collected in 2013), we investigated the causal relationship between the number of biological children and their parents’ number of missing natural teeth. Thereby, we exploited random natural variation in family size resulting from (i) the birth of multiples vs singletons, and (ii) the sex composition of the two first-born children (increased likelihood of a third child if the two first-born children have the same sex).Results2SLS regressions detected a strong causal relationship between the number of children and teeth for women but not for men when an additional birth occurred after the first two children had the same sex. Women then had an average of 4.27 (95% CI: 1.08 to 7.46) fewer teeth than women without an additional birth whose first two children had different sexes.ConclusionsThis study provides novel evidence for causal links between the number of children and the number of missing teeth. An additional birth might be detrimental to the mother’s but not the father’s oral health.
Genetic and phenotypic difference in CD8+ T cell exhaustion between chronic hepatitis B infection and hepatocellular carcinoma
Authors: Wang Xiaochen , He Qifeng , Shen Haiyuan , Lu Xiao-Jie , Sun Beicheng 
Published: April 2018

BackgroundSeveral recent studies published have suggested that T cell exhaustion exists both in chronic infection and cancer. However, to date, few studies have investigated their differences. Here we designed this study to explore the genetic and phenotypic difference in CD8+ T cell exhaustion between chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC).MethodsIn this study, we assayed the phenotypes and functional states of CD8+ T cells separating from human CHB tissues and HCC tissues, and re-analyse the single-cell sequencing data (GSE98638) published previously. Clustering analysis of genes was performed using the T cell exhaustion gene modules (modules 1–4) proposed by Speiseret al.ResultsCD8+ T cells from liver tissues of both CHB and HCC showed high levels of exhaustion markers, DOI: programmed cell death-1 (PD-1), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), and lymphocyte-activation gene 3 (LAG-3), decreased proliferation (Ki67) and cell activity (CD69), and reduced production of effector cytokines (interferon-γ, interleukin-2 and tumour necrosis factor-α). Compared with CD8+ T cells from CHB tissues, those from HCC tissue showed higher expression levels of exhaustion markers, lower levels of proliferation, cell activity and the production of effector cytokines. Cluster analysis showed that exhaustion associated genes in CHB and HCC are inclined to distribute into modules 3 while those isolated from HCC into modules 1 and 2.ConclusionsCD8+ T cell exhaustion existed both in CHB and HCC, but the phenotypes, functional states and underlying mechanisms are somewhat different between the two.
Does magnesium sulfate have a role in the management of severe traumatic brain injury in civilian and military populations? A systematic review and meta-analysis
Authors: Lyons Marc W H , Blackshaw W J 
Published: April 2018

IntroductionTraumatic brain injury (TBI) is a significant cause of combat morbidity. Currently, the medical management of TBI is limited to supportive critical care. Magnesium sulfate has been studied as a potentially beneficial therapeutic agent.MethodsA systematic review and meta-analysis was undertaken, examining the role of magnesium in the management of severe TBI in adults. The primary outcome of the study was all-cause mortality, with secondary outcomes of Glasgow Outcome Score (GOS) and GCS. EMBASE, MEDLINE, CINAHL, WHO Trial Registry and the Cochrane Library database were systematically searched, with data included until 1 February 2017. Inclusion criteria were: human study; aged >13 years; randomised controlled trial; severe TBI. Exclusion criteria were: data collected prior to 1 January 2002; magnesium commenced >24 hours postinjury; magnesium therapy for <24 hours. Statistical analysis was conducted using Stata (V.13.1).ResultsThe pooled results of six studies found all-cause mortality not to be significantly different in the treatment group (RR 0.84, 95% CI 0.54 to 1.33; P=0.46) with an I2value of >70%. With regard to the secondary outcomes, no significant difference in GOS scores between treatment and control was demonstrated. GCS showed a significant improvement in the treatment group.ConclusionsThe meta-analysis found a lack of evidence for magnesium pharmacotherapy in severe TBI, although the data were noted to be conflicting and significantly heterogeneous. Further study is recommended to ascertain whether a therapeutic window exists for magnesium in severe TBI.
Thrombectomy for acute ischemic stroke in the elderly: a ‘real world’ experience
Authors: Alawieh Ali , Chatterjee Arindam , Feng Wuwei , Porto Guilherme , Vargas Jan , Kellogg Ryan , Turk Aquilla S , Turner Raymond D , Imran Chaudry M , Spiotta Alejandro M 
Published: April 2018

IntroductionCompleted randomized trials on endovascular thrombectomy (ET) did not independently assess the efficacy of ET in the elderly (≥80 years old) who were often excluded or under-represented in trials. There were also inconsistent criteria for patient selection in this population across the different trials. This work evaluates outcomes after ET for acute ischemic stroke (AIS) in the elderly at a high volume stroke center.MethodsWe reviewed all cases of AIS that underwent a direct aspiration first pass technique (ADAPT) thrombectomy for large vessel occlusions between March 2013 and October 2017 while comparing outcomes in the elderly with younger counterparts. We also reviewed AIS cases in elderly patients undergoing medical management who were matched to the ET counterparts by demographics, comorbidities, baseline deficits, and stroke severity.ResultsOf 560 patients undergoing ET for AIS, 108 patients were in the elderly group (≥80 years of age), and had a significantly lower likelihood of functional independence (defined as a modified Rankin Scale score of 0–2) at 90 days compared with younger patients (20.5% vs 44.4%, P<0.001), and higher mortality rates (34.3% vs 20%, P<0.001). When compared with patients undergoing medical management, elderly patients did not have a significant improvement in rates of good outcomes (20.5% vs 19.5%, P>0.05), and had significantly higher rates of hemorrhage (40.7% vs 9.3%, P<0.001). We also identified baseline stroke severity and the incidence of hemorrhage as two independent predictors of outcome in the elderly patients.ConclusionsET in the elderly did not show a similar benefit to younger patients when compared with medical management. These findings emphasize the need for more optimal selection criteria for the elderly population to improve the risk to benefit ratio of ET.
Multiyear variations in High Arctic river temperatures in response to climate variability
Authors: Bolduc Christopher , Lamoureux Scott F. 
Published: April 2018

Water temperature measurements (2004–2016) from two small rivers in the High Arctic were analyzed to determine the effects of climate variability on thermal regime and the sensitivity to climate change. The East and West rivers (unofficial names) drain similar watersheds (11.6 and 8.0 km2, respectively) and are located at the Cape Bounty Arctic Watershed Observatory (CBAWO), Melville Island, Canada (74°55′N, 109°35′W). Differences in seasonal timing of river temperatures were evident when comparing the coldest and warmest years of the study period, and across different discharge conditions. Snowmelt runoff is characterized by uniformly cold water (∼0–1 °C) over a wide range of discharge conditions, followed by warming water temperatures during flow recession. The rivers showed varying sensitivity to mid-summer air temperature conditions in a given year, with warmer years indicating high correlation (r2 = 0.794–0.929), whereas colder years showed reduced correlation (r2 = 0.368–0.778). River temperatures reached levels which are reported to negatively affect fish and other cold-water aquatic species (>18 °C) with greater frequency and duration during the warmest years. These results provide a basis to further enhance prediction of river thermal conditions to assess ecosystem health in a river system and to refine insights into the effects of climate change on High Arctic aquatic ecosystems.
Structure of the crust and upper mantle beneath the Parnaíba Basin, Brazil, from wide-angle reflection–refraction data
Authors: Soares José E. P. , Stephenson Randell , Fuck Reinhardt A. , de Lima Marcus V. A. G. , de Araújo Vitto C. M. , Lima Flávio T. , Rocha Fábio A. S. , da Trindade Cíntia R. 
Published: April 2018

Abstract
The Parnaíba Basin is a Phanerozoic intracontinental basin within the South America plate, lying on top of and within Precambrian terranes. The Parnaíba Basin Analysis Program wide-angle reflection–refraction (WARR) lies east–west and is 1150 km long profile crossing the basin and its margins. The WARR results show that the crust and uppermost mantle along the profile consist of the Amazonian Craton and Borborema Province, and the Grajaú and Teresina domains comprising the Parnaíba block hidden below the sedimentary cover of the basin itself. The lithospheric characteristics of the Parnaíba block and their differences from the adjacent Precambrian Amazonian Craton and Borborema Province elucidate some aspects of the present day existence of the sedimentary basin covering it. Important elements include the presence of a high mantle velocity and high-velocity lowermost crustal region, interpreted as linked to the intrusion of mafic material into the crust underlying the Grajaú domain, and indications that the crust in this area has been intruded since its consolidation in the Neoproterozoic. It is tentatively proposed that magmatism is related to the inferred thinning of the lower crust of the Teresina and Borborema segments of the profile, with this, in turn, linked to Cretaceous extensional tectonics and the opening of the South Atlantic Ocean.
Deptor Is a Novel Target of Wnt/β-Catenin/c-Myc and Contributes to Colorectal Cancer Cell Growth
Authors: Wang Qingding , Zhou Yuning , Rychahou Piotr , Harris Jennifer W. , Zaytseva Yekaterina Y. , Liu Jinpeng , Wang Chi , Weiss Heidi L. , Liu Chunming , Lee Eun Y. , Evers B. Mark 
Published: April 2018

Abstract
Activation of the Wnt/β-catenin signaling pathway drives colorectal cancer growth by deregulating expression of downstream target genes, including the c-myc proto-oncogene. The critical targets that mediate the functions of oncogenic c-Myc in colorectal cancer have yet to be fully elucidated. Previously, we showed that activation of PI3K/Akt/mTOR contributes to colorectal cancer growth and metastasis. Here, we show that Deptor, a suppressor of mTOR, is a direct target of Wnt/β-catenin/c-Myc signaling in colorectal cancer cells. Inhibition of Wnt/β-catenin or knockdown of c-Myc decreased, while activation of Wnt/β-catenin or overexpression of c-Myc increased the expression of Deptor. c-Myc bound the promoter of Deptor and transcriptionally regulated Deptor expression. Inhibition of Wnt/β-catenin/c-Myc signaling increased mTOR activation, and the combination of Wnt and Akt/mTOR inhibitors enhanced inhibition of colorectal cancer cell growth in vitro and in vivo. Deptor expression was increased in colorectal cancer cells; knockdown of Deptor induced differentiation, decreased expression of B lymphoma Mo-MLV insertion region 1 (Bmi1), and decreased proliferation in colorectal cancer cell lines and primary human colorectal cancer cells. Importantly, our work identifies Deptor as a downstream target of the Wnt/β-catenin/c-Myc signaling pathway, acting as a tumor promoter in colorectal cancer cells. Moreover, we provide a molecular basis for the synergistic combination of Wnt and mTOR inhibitors in treating colorectal cancer with elevated c-Myc.
Significance: The mTOR inhibitor DEPTOR acts as a tumor promoter and could be a potential therapeutic target in colorectal cancer. Cancer Res; 78(12); 3163–75. ©2018 AACR.
Strategic Therapeutic Targeting to Overcome Venetoclax Resistance in Aggressive B-cell Lymphomas
Authors: Pham Lan V. , Huang Shengjian , Zhang Hui , Zhang Jun , Bell Taylor , Zhou Shouhao , Pogue Elizabeth , Ding Zhiyong , Lam Laura , Westin Jason , Davis R. Eric , Young Ken H. , Medeiros L. Jeffrey , Ford Richard J. , Nomie Krystle , Zhang Leo , Wang Michael 
Published: April 2018

Abstract
Purpose: B-cell lymphoma-2 (BCL-2), an antiapoptotic protein often dysregulated in B-cell lymphomas, promotes cell survival and provides protection from stress. A recent phase I first-in-human study of the BCL-2 inhibitor venetoclax in non-Hodgkin lymphoma showed an overall response rate of 44%. These promising clinical results prompted our examination of the biological effects and mechanism of action underlying venetoclax activity in aggressive B-cell lymphoma, including mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL).
Experimental Design: MCL and DLBCL cell lines, primary patient samples, and in vivo patient-derived xenograft (PDX) models were utilized to examine venetoclax efficacy. Furthermore, the mechanisms underlying venetoclax response and the development of venetoclax resistance were evaluated using proteomics analysis and Western blotting.
Results: Potential biomarkers linked to venetoclax activity and targeted combination therapies that can augment venetoclax response were identified. We demonstrate that DLBCL and MCL cell lines, primary patient samples, and PDX mouse models expressing high BCL-2 levels are extremely sensitive to venetoclax treatment. Proteomics studies showed that venetoclax substantially alters the expression levels and phosphorylation status of key proteins involved in cellular processes, including the DNA damage response, cell metabolism, cell growth/survival, and apoptosis. Short- and long-term exposure to venetoclax inhibited PTEN expression, leading to enhanced AKT pathway activation and concomitant susceptibility to PI3K/AKT inhibition. Intrinsic venetoclax-resistant cells possess high AKT activation and are highly sensitive to PI3K/AKT inhibition.
Conclusions: These findings demonstrate the on-target effect of venetoclax and offer potential mechanisms to overcome acquired and intrinsic venetoclax resistance through PI3K/AKT inhibition. Clin Cancer Res; 24(16); 3967–80. ©2018 AACR.
Ventricular Assist Device Utilization in Heart Transplant Candidates
Authors: Truby Lauren K. , Garan A. Reshad , Givens Raymond C. , Takeda Koji , Takayama Hiroo , Trinh Pauline N. , Yuzefpolskaya Melana , Farr Maryjane A. , Naka Yoshifumi , Colombo Paolo C. , Topkara Veli K. 
Published: April 2018

Background:
Continuous-flow left ventricular assist devices (CF-LVADs) have become a standard treatment choice in advanced heart failure patients. We hypothesized that practice patterns with regards to CF-LVAD utilization vary significantly among transplant centers and impact waitlist outcomes.

Methods and Results:

The United Network for Organ Sharing registry was queried to identify adult patients who were waitlisted for heart transplantation (HT) between 2008 and 2015. Each patient was assigned a propensity score based on likelihood of receiving a durable CF-LVAD before or while waitlisted. The primary outcomes of interest were death or delisting for worsening status and HT at 1 year. A total of 22 863 patients from 92 centers were identified. Among these, 9013 (39.4%) were mechanically supported. CF-LVAD utilization varied significantly between and within United Network for Organ Sharing regions. Freedom from waitlist death or delisting was significantly lower in propensity-score–matched patients who were mechanically supported versus medically managed (83.5% versus 79.2%;
P
<0.001). However, cumulative incidence of HT was also lower in mechanically supported patients (53.3% versus 63.6%;
P
<0.001). Congruous mechanical and medical bridging strategies based on clinical risk profile were associated with lower risk of death or delisting (hazard ratio, 0.88;
P
=0.027) and higher likelihood of HT (hazard ratio, 1.14;
P
<0.001).

Conclusions:
CF-LVAD utilization may lower waitlist mortality at the expense of lower likelihood of HT. Decision to use CF-LVAD and timing of transition should be individualized based on patient-, center-, and region-level risk factors to achieve optimal outcomes.
B-Type Natriuretic Peptide Assessment in Patients Undergoing Revascularization for Left Main Coronary Artery Disease
Authors: Redfors Björn , Chen Shmuel , Crowley Aaron , Ben-Yehuda Ori , Gersh Bernard J. , Lembo Nicholas J. , Brown W. Morris , Banning Adrian P. , Taggart David P. , Serruys Patrick W. , Kappetein Arie Pieter , Sabik Joseph F. , Stone Gregg W. 
Published: April 2018

Background:
Elevated B-type natriuretic peptide (BNP) is reflective of impaired cardiac function and is associated with worse prognosis among patients with coronary artery disease (CAD). We sought to assess the association between baseline BNP, adverse outcomes, and the relative efficacy of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) in patients with left main CAD.

Methods:
The EXCEL trial (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) randomized patients with left main CAD and low or intermediate SYNTAX scores (Synergy Between PCI With TAXUS and Cardiac Surgery) to PCI with everolimus-eluting stents versus CABG. The primary end point was the composite of all-cause death, myocardial infarction, or stroke. We used multivariable Cox proportional hazards regression to assess the associations between normal versus elevated BNP (≥100 pg/mL), randomized treatment, and the 3-year risk of adverse events.

Results:

BNP at baseline was elevated in 410 of 1037 (39.5%) patients enrolled in EXCEL. Patients with elevated BNP levels were older and more frequently had additional cardiovascular risk factors and lower left ventricular ejection fraction than those with normal BNP, but had similar SYNTAX scores. Patients with elevated BNP had significantly higher 3-year rates of the primary end point (18.6% versus 11.7%; adjusted hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.16–2.28;
P
=0.005) and higher mortality (11.5% versus 3.9%; adjusted HR, 2.49; 95% CI, 1.48–4.19;
P
=0.0006), both from cardiovascular and noncardiovascular causes. In contrast, there were no significant differences in the risks of myocardial infarction, stroke, ischemia-driven revascularization, stent thrombosis, graft occlusion, or major bleeding. A significant interaction (
P
interaction
=0.03) was present between elevated versus normal BNP and treatment with PCI versus CABG for the adjusted risk of the primary composite end point at 3 years among patients with elevated BNP (adjusted HR for PCI versus CABG, 1.54; 95% CI, 0.96–2.47) versus normal BNP (adjusted HR, 0.74; 95% CI, 0.46–1.20). This interaction was stronger when log(BNP) was modeled as a continuous variable (
P
interaction
=0.002).

Conclusions:
In the EXCEL trial, elevated baseline BNP levels in patients with left main CAD undergoing revascularization were independently associated with long-term mortality but not nonfatal adverse ischemic or bleeding events. The relative long-term outcomes after PCI versus CABG for revascularization of left main CAD may be conditioned by the baseline BNP level.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01205776.
Association of Peripheral Artery Disease With Incident Atrial Fibrillation: The ARIC (Atherosclerosis Risk in Communities) Study
Authors: Bekwelem Wobo , Norby Faye L. , Agarwal Sunil K. , Matsushita Kunihiro , Coresh Josef , Alonso Alvaro , Chen Lin Y. 
Published: April 2018

Background

Although peripheral artery disease as defined by ankle‐brachial index (
ABI
) is associated with incident atrial fibrillation (
AF
), questions remain about the risk of
AF
in borderline
ABI
(>0.90 to <1.0) or noncompressible arteries (>1.4). We evaluated the association of borderline
ABI
and
ABI
>1.4 in the ARIC (Atherosclerosis Risk in Communities) study, a population‐based prospective cohort study.

Methods and Results

We included 14 794 participants (age, 54.2±5.8 years, 55% women, 26% blacks) with
ABI
measured at the baseline (1987–1989) and without
AF
.
AF
was identified from hospital records, death certificates, and ECGs. Using Cox proportional hazards, we evaluated the association between
ABI
and
AF
. During a median follow‐up of 23.3 years, there were 2288
AF
cases. After adjustment for cardiovascular risk factors, hazard ratio (
HR
) (95% confidence interval) for
AF
among individuals with
ABI
<1.0 compared with
ABI
1.0 to 1.4, was 1.13 (1.01–1.27).
ABI
>1.4 was not associated with increased
AF
risk.
ABI
≤0.9 and borderline
ABI
were associated with a higher risk of
AF
compared with
ABI
1.0 to 1.4. Demographics‐adjusted
HR
s (95% confidence interval) were 1.43 (1.17–1.75) and 1.32 (1.16–1.50), respectively. However, the associations of
ABI
≤0.9 and borderline
ABI
with
AF
were attenuated after adjusting for cardiovascular risk factors (
HR
[95% confidence interval], 1.10 [0.90–1.34] and 1.14 [1.00–1.30]), respectively.

Conclusions

Peripheral artery disease indicated by low
ABI
, including borderline
ABI
, is a weak risk factor for
AF
.
ABI
>1.4 is not associated with an increased
AF
risk. The relationship between peripheral artery disease and
AF
appears to be mostly explained by traditional atherosclerotic risk factors.