bluuebunny/crossref_metadata_2025_split huggingface dataset:
The pattern of paediatric blast injury in Afghanistan
Authors: Thompson Daniel C , Crooks R J , Clasper J C , Lupu A , Stapley S A , Cloke D J 
Published: October 2017

IntroductionBetween 2009 and 2015, 3746 children died, and 7904 were injured as a result of armed conflict within Afghanistan. Improvised explosive devices (IEDs) and explosive remnants of war accounted for 29% of child casualties in 2015. The aim of this study was to review the burden of paediatric blast injuries admitted to Camp Bastion, Afghanistan, and to investigate the hypothesis that children suffer proportionally more head injuries than adults.MethodA retrospective analysis was undertaken of prospectively collected data derived from the UK Joint Theatre Trauma Registry of ambulant paediatric (aged 2–15 years) admissions with blast injuries at the Role 3 Field Hospital, Camp Bastion from June 2006 to March 2013. The data set included demographic information, injury profile and severity (New Injury Severity Score) and operative findings. The pattern of injuries were investigated by looking at trends in the number and severity of injuries sustained by each body region.ResultsDuring this period, 295 admissions were identified, 76% of whom were male, with an overall mortality rate of 18.5%. The most common blast mechanism was an IED (68%) causing 80% of fatalities. The lower extremities were the most commonly injured body region, accounting for 31% of total injuries and occurring in 62% of cases. 24.3% of children between 2 and 7 years suffered severe head or neck injuries compared with 19.8% of children aged between 8 and 15 years. 34% of head injuries were rated unsurvivable and accounted for 88% of fatalities. 77% of cases required an operation with a mean operating time of 125 min. The most common first operations were debridement of soft tissues (50%), laparotomy (16%) and lower limb amputation (11%).ConclusionAlthough paediatric blast casualties represented a small percentage of the overall workload at Camp Bastion Role 3 Medical Facility, the pattern of injuries seen suggests that children are more likely to sustain severe head, face and neck injuries than adults.
Prenatal exposure to glycol ethers and cryptorchidism and hypospadias: a nested case–control study
Authors: Warembourg Charline , Botton Jérémie , Lelong Nathalie , Rouget Florence , Khoshnood Babak , Le Gléau Florent , Monfort Christine , Labat Laurence , Pierre Fabrice , Heude Barbara , Slama Rémy , Multigner Luc , Charles Marie-Aline , Cordier Sylvaine , Garlantézec Ronan 
Published: October 2017

ObjectivesGlycol ethers (GE) are oxygenated solvents frequently found in occupational and consumer products. Some of them are well-known testicular and developmental animal toxicants. This study aims to evaluate the risk of male genital anomalies in association with prenatal exposure to GE using urinary biomarkers of exposure.MethodsWe conducted a case–control study nested in two joint mother–child cohorts (5303 pregnant women). Cases of cryptorchidism and hypospadias were identified at birth and confirmed during a 2-year follow-up period (n=14 cryptorchidism and n=15 hypospadias). Each case was matched to three randomly selected controls within the cohorts for region of inclusion and gestational age at urine sampling. Concentrations of five GE acidic metabolites were measured in spot maternal urine samples collected during pregnancy. ORs were estimated with multivariate conditional logistic regressions including a Firth’s penalisation.ResultsDetection rates of urinary GE metabolites ranged from 8% to 93% and only two were sufficiently detected (>33%) in each cohort to be studied: methoxyacetic acid (MAA) and phenoxyacetic acid (PhAA). A significantly higher risk of hypospadias was associated with the highest tertile of exposure to MAA: OR (95% CI) 4.5(1.4 to 23.4). No association were observed with urinary concentration of PhAA, nor with the risk of cryptorchidism.ConclusionsIn view of the toxicological plausibility of our results, this study, despite its small sample size, raises concern about the potential developmental toxicity of MAA on the male genital system and calls for thorough identification of current sources of exposure to MAA.
Long-term follow-up for cancer incidence in a cohort of Danish firefighters
Authors: Kirstine Ugelvig Petersen Kajsa , Pedersen Julie Elbaek , Bonde Jens Peter , Ebbehoej Niels Erik , Hansen Johnni 
Published: October 2017

ObjectivesTo examine cancer incidence among Danish firefighters using several employment-related exposure subgroups.MethodsA historical cohort of 9061 male Danish firefighters was established from collected personnel and membership records from employers and trade unions. Using the unique Danish personal identification number, information on additional previous employment, cancer and vital status was linked to members of the cohort from the Supplementary Pension Fund Register, the Danish Cancer Registry and the Danish Civil Registration System. SIRs were calculated for specific cancer types using rates for the general population, a sample of the working population and military employees, respectively.ResultsCompared with the selected reference groups, the overall observed incidence of cancer among the firefighters was at level with the expected (SIR 1.02, 95% CI 0.96 to 1.09 vs the general population). The SIR for colon cancer was consistently significantly reduced, while the slight excess seen for melanoma of the skin, prostate and testicular cancer compared with the general population was not reproduced using the military as reference.ConclusionsPrevious associations with melanoma of the skin, prostate and testicular cancer are supported by our main results. However, the increase in incidence of these cancers is not reproduced using the military as reference. Similarities in cancer profile for the firefighters and the military point to shared risk factors in either lifestyle or work environment.
Association of QT interval with mortality by kidney function: results from the National Health and Nutrition Examination Survey (NHANES)
Authors: Malik Rehan , Waheed Sehrish , Parashara Deepak , Perez Jorge , Waheed Salman 
Published: October 2017

ObjectiveProlonged QT interval predisposes to ventricular arrhythmias and sudden cardiac death. However, the association between QT interval and mortality by the level of pre-existing kidney function has not been investigated.MethodsWe followed 6565 participants from the National Health and Nutrition Examination Survey III for a median of 13.3 years. Sample divided according to corrected QT (QTc) interval was as follows: normal (QTc <450 ms for men and <460 ms for women) or prolonged. It was further categorised as follows: (1) no chronic kidney disease (CKD), that is, albumin to creatinine ratio (ACR) <30 mg/g and estimated glomerular filtration rate (eGFR)>60 mL/min/1.73 m2; (2) CKD by eGFR only (eGFR <60 mL/min/1.73 m2, ACR <30 mg/g); (3) CKD by ACR only (ACR >30 mg/g, eGFR >60 mL/min/1.73 m2) and (4) CKD by both. Cox proportional hazards models were used.ResultsCKD group had prolonged QTc than those without CKD (20.5%vs12.9%, p<0.0001). Both prolonged QTc and CKD are independently associated with increased risk of mortality. When combined, risk of mortality is higher in those with CKD by eGFR with prolonged QTc than normal QTc (HR 2.6 (1.7–3.9) and 3.1 (1.7–5.4) vs 1.4 (1.1–1.7) and 1.7 (1.3–2.1) for all-cause and CV mortality). There is no significant difference in risk in those with CKD by ACR when QTc is prolonged. There is significant improvement in risk prediction for all-cause and CV mortality when QTc is added to CKD beyond established CV risk factors (net reclassification index p<0.00001).ConclusionA screening ECG in those with CKD may help in finer risk stratification and may be considered.
Improving paediatric residents’ knowledge and perspectives regarding the insulin pump using a novel educational workshop
Authors: Bansal Shipra , Marwa Albara , Kasturi Kannan , Perez-Colon Sheila 
Published: October 2017

AbstractObjectivesAs a pilot study, we aimed to investigate the knowledge and perceptions of categorical paediatric residents (RES) at our institution regarding insulin pumps (IPs) and the impact following a targeted workshop.MethodsAll RES at our institution in attendance at a routine noon conference participated in a workshop, completing an anonymous survey before and right after the intervention to evaluate knowledge, attitudes and self-reported comfort regarding IPs. The workshop consisted of a didactic lecture followed by an insulin pump (IP) device demonstration of three commonly available brands. Knowledge score (KS) was calculated for each RES based on the total correct responses. Attitudes were assessed via 5-point Likert scale. Frequencies, t-test and McNemar tests were used to analyse data.ResultsThirty four completed surveys were analysed out of 49 RES (69.3%) who attended the workshop. Among them, there were 19 first-year, 8 second-year and 7 third-year residents. Following the intervention, KS increased significantly (p&lt;0.001) with progression in residents’ attitudes. Overall, more RES reported being comfortable with handling the IP, including looking up and changing the settings (p&lt;0.001).ConclusionThere is scope for improvement in the knowledge and perceptions of RES regarding IPs. Educational interventions like ours are needed to familiarise our future physicians with IPs to allow hospitals to provide their systematic and safe inpatient use.
Endothelial function is impaired in the cutaneous microcirculation of adults with psoriasis through reductions in nitric oxide-dependent vasodilation
Authors: Alba Billie K. , Greaney Jody L. , Ferguson Sara B. , Alexander Lacy M. 
Published: October 2017

Psoriasis is an independent risk factor for cardiovascular disease; however, the underlying mechanisms are not fully understood. Deficits in conduit arterial function are evident in patients with psoriasis, but potential impairments in microcirculatory endothelial function remain unclear. We hypothesized that cutaneous microvascular dysfunction would be detectable in otherwise healthy individuals with psoriasis. Two intradermal microdialysis fibers were placed in (nonlesional) forearm skin of nine patients (3 men and 6 women, 39 ± 5 yr) with moderate (16 ± 2% of body surface area) plaque psoriasis and nine healthy (nonpsoriatic) control subjects (3 men and 6 women, 38 ± 5 yr) for local delivery of 1) lactated Ringer solution (control) and 2) 10 mM l-ascorbate (a nonspecific antioxidant). An index of skin blood flow was measured using laser-Doppler flowmetry during local heating (42°C). Nitric oxide (NO)-dependent vasodilation was directly quantified after perfusion of the nonspecific NO synthase inhibitor NG-nitro-l-arginine methyl ester (15 mM). A third fiber was perfused with increasing concentrations (10−10– 10−2M) of norepinephrine to elicit adrenoreceptor-mediated cutaneous vasoconstriction. NO-dependent vasodilation was attenuated in patients with psoriasis (57 ± 5% and 39 ± 7% maximum cutaneous vascular conductance in control subjects and adults with psoriasis, respectively, P < 0.01). l-Ascorbate did not improve NO-dependent vasodilation ( P > 0.05). There was no group difference in maximal vasoconstriction or microvascular sensitivity to norepinephrine ( P > 0.05). These data suggest that NO bioavailability is reduced in otherwise healthy individuals with psoriasis, which contributes to systemic microvascular dysfunction.NEW & NOTEWORTHY In adults with psoriasis, reduced nitric oxide bioavailability mediates impaired endothelium-dependent vasodilation, independent of increases in oxidative stress. Furthermore, the degree of psoriatic symptomology is directly related to greater reductions in nitric oxide-dependent vasodilation.
Chronic femoral artery ligation exaggerates the pressor and sympathetic nerve responses during dynamic skeletal muscle stretch in decerebrate rats
Authors: Kempf Evan A. , Rollins Korynne S. , Hopkins Tyler D. , Butenas Alec L. , Santin Joseph M. , Smith Joshua R. , Copp Steven W. 
Published: October 2017

Mechanical and metabolic signals arising during skeletal muscle contraction reflexly increase sympathetic nerve activity and blood pressure (i.e., the exercise pressor reflex). In a rat model of simulated peripheral artery disease in which a femoral artery is chronically (~72 h) ligated, the mechanically sensitive component of the exercise pressor reflex during 1-Hz dynamic contraction is exaggerated compared with that found in normal rats. Whether this is due to an enhanced acute sensitization of mechanoreceptors by metabolites produced during contraction or involves a chronic sensitization of mechanoreceptors is unknown. To investigate this issue, in decerebrate, unanesthetized rats, we tested the hypothesis that the increases in mean arterial blood pressure and renal sympathetic nerve activity during 1-Hz dynamic stretch are larger when evoked from a previously “ligated” hindlimb compared with those evoked from the contralateral “freely perfused” hindlimb. Dynamic stretch provided a mechanical stimulus in the absence of contraction-induced metabolite production that closely replicated the pattern of the mechanical stimulus present during dynamic contraction. We found that the increases in mean arterial blood pressure (freely perfused: 14 ± 1 and ligated: 23 ± 3 mmHg, P = 0.02) and renal sympathetic nerve activity were significantly greater during dynamic stretch of the ligated hindlimb compared with the increases during dynamic stretch of the freely perfused hindlimb. These findings suggest that the exaggerated mechanically sensitive component of the exercise pressor reflex found during dynamic muscle contraction in this rat model of simulated peripheral artery disease involves a chronic sensitizing effect of ligation on muscle mechanoreceptors and cannot be attributed solely to acute contraction-induced metabolite sensitization. NEW & NOTEWORTHY We found that the pressor and sympathetic nerve responses during dynamic stretch were exaggerated in rats with a ligated femoral artery (a model of peripheral artery disease). Our findings provide mechanistic insights into the exaggerated exercise pressor reflex in this model and may have important implications for peripheral artery disease patients.
ALK Inhibitor Response in Melanomas Expressing EML4-ALK Fusions and Alternate ALK Isoforms
Authors: Couts Kasey L. , Bemis Judson , Turner Jacqueline A. , Bagby Stacey M. , Murphy Danielle , Christiansen Jason , Hintzsche Jennifer D. , Le Anh , Pitts Todd M. , Wells Keith , Applegate Allison , Amato Carol , Multani Pratik , Chow-Maneval Edna , Tentler John J. , Shellman Yiqun G. , Rioth Matthew J. , Tan Aik-Choon , Gonzalez Rene , Medina Theresa , Doebele Robert C. , Robinson William A. 
Published: October 2017

Abstract
Oncogenic ALK fusions occur in several types of cancer and can be effectively treated with ALK inhibitors; however, ALK fusions and treatment response have not been characterized in malignant melanomas. Recently, a novel isoform of ALK (ALKATI) was reported in 11% of melanomas but the response of melanomas expressing ALKATI to ALK inhibition has not been well characterized. We analyzed 45 melanoma patient-derived xenograft models for ALK mRNA and protein expression. ALK expression was identified in 11 of 45 (24.4%) melanomas. Ten melanomas express wild-type (wt) ALK and/or ALKATI and one mucosal melanoma expresses multiple novel EML4-ALK fusion variants. Melanoma cells expressing different ALK variants were tested for response to ALK inhibitors. Whereas the melanoma expressing EML4-ALK were sensitive to ALK inhibitors in vitro and in vivo, the melanomas expressing wt ALK or ALKATI were not sensitive to ALK inhibitors. In addition, a patient with mucosal melanoma expressing ALKATI was treated with an ALK/ROS1/TRK inhibitor (entrectinib) on a phase I trial but did not respond. Our results demonstrate ALK fusions occur in malignant melanomas and respond to targeted therapy, whereas melanomas expressing ALKATI do not respond to ALK inhibitors. Targeting ALK fusions is an effective therapeutic option for a subset of melanoma patients, but additional clinical studies are needed to determine the efficacy of targeted therapies in melanomas expressing wt ALK or ALKATI. Mol Cancer Ther; 17(1); 222–31. ©2017 AACR.
Theranostic Radiolabeled Anti-CD20 sdAb for Targeted Radionuclide Therapy of Non-Hodgkin Lymphoma
Authors: Krasniqi Ahmet , D'Huyvetter Matthias , Xavier Catarina , Van der Jeught Kevin , Muyldermans Serge , Van Der Heyden José , Lahoutte Tony , Tavernier Jan , Devoogdt Nick 
Published: October 2017

Abstract
Anti-CD20 radioimmunotherapy is an effective approach for therapy of relapsed or refractory CD20pos lymphomas, but faces limitations due to poor tumor penetration and undesirable pharmacokinetics of full antibodies. Camelid single-domain Ab fragments (sdAb) might circumvent some of the limitations of radiolabeled full antibodies. In this study, a set of hCD20-targeting sdAbs was generated, and their capacity to bind hCD20 was evaluated in vitro and in vivo. A lead sdAb, sdAb 9079, was selected on the basis of its specific tumor targeting and significant lower kidney accumulation compared with other sdAbs. SdAb 9079 was then radiolabeled with 68Ga and 177Lu for PET imaging and targeted therapy. The therapeutic potential of 177Lu-DTPA-sdAb was compared with that of 177Lu-DTPA-rituximab and unlabeled rituximab in mice bearing hCD20pos tumors. Radiolabeled with 68Ga, sdAb 9079 showed specific tumor uptake, with very low accumulation in nontarget organs, except kidneys. The tumor uptake of 177Lu-DTPA-sdAb 9079 after 1.5 h was 3.4 ± 1.3% ID/g, with T/B and T/M ratios of 13.3 ± 4.6 and 32.9 ± 15.6. Peak tumor accumulation of 177Lu-DTPA-rituximab was about 9 times higher, but concomitantly with high accumulation in nontarget organs and very low T/B and T/M ratios (0.8 ± 0.1 and 7.1 ± 2.4). Treatment of mice with 177Lu-DTPA-sdAb 9079 significantly prolonged median survival compared with control groups and was as effective as treatment with rituximab or its 177Lu-labeled variant. Taken together, sdAb 9079 displays promising features as a theranostic drug to treat CD20pos lymphomas. Mol Cancer Ther; 16(12); 2828–39. ©2017 AACR.
Suppression of Adaptive Responses to Targeted Cancer Therapy by Transcriptional Repression
Authors: Rusan Maria , Li Kapsok , Li Yvonne , Christensen Camilla L. , Abraham Brian J. , Kwiatkowski Nicholas , Buczkowski Kevin A. , Bockorny Bruno , Chen Ting , Li Shuai , Rhee Kevin , Zhang Haikuo , Chen Wankun , Terai Hideki , Tavares Tiffany , Leggett Alan L. , Li Tianxia , Wang Yichen , Zhang Tinghu , Kim Tae-Jung , Hong Sook-Hee , Poudel-Neupane Neermala , Silkes Michael , Mudianto Tenny , Tan Li , Shimamura Takeshi , Meyerson Matthew , Bass Adam J. , Watanabe Hideo , Gray Nathanael S. , Young Richard A. , Wong Kwok-Kin , Hammerman Peter S. 
Published: October 2017

Abstract
Acquired drug resistance is a major factor limiting the effectiveness of targeted cancer therapies. Targeting tumors with kinase inhibitors induces complex adaptive programs that promote the persistence of a fraction of the original cell population, facilitating the eventual outgrowth of inhibitor-resistant tumor clones. We show that the addition of a newly identified CDK7/12 inhibitor, THZ1, to targeted therapy enhances cell killing and impedes the emergence of drug-resistant cell populations in diverse cellular and in vivo cancer models. We propose that targeted therapy induces a state of transcriptional dependency in a subpopulation of cells poised to become drug tolerant, which THZ1 can exploit by blocking dynamic transcriptional responses, promoting remodeling of enhancers and key signaling outputs required for tumor cell survival in the setting of targeted therapy. These findings suggest that the addition of THZ1 to targeted therapies is a promising broad-based strategy to hinder the emergence of drug-resistant cancer cell populations.
Significance: CDK7/12 inhibition prevents active enhancer formation at genes, promoting resistance emergence in response to targeted therapy, and impedes the engagement of transcriptional programs required for tumor cell survival. CDK7/12 inhibition in combination with targeted cancer therapies may serve as a therapeutic paradigm for enhancing the effectiveness of targeted therapies. Cancer Discov; 8(1); 59–73. ©2017 AACR.
See related commentary by Carugo and Draetta, p. 17.
This article is highlighted in the In This Issue feature, p. 1
Cardiovascular Health in African Americans: A Scientific Statement From the American Heart Association
Authors: Carnethon Mercedes R. , Pu Jia , Howard George , Albert Michelle A. , Anderson Cheryl A.M. , Bertoni Alain G. , Mujahid Mahasin S. , Palaniappan Latha , Taylor Herman A. , Willis Monte , Yancy Clyde W. 
Published: October 2017

Background and Purpose:
Population-wide reductions in cardiovascular disease incidence and mortality have not been shared equally by African Americans. The burden of cardiovascular disease in the African American community remains high and is a primary cause of disparities in life expectancy between African Americans and whites. The objectives of the present scientific statement are to describe cardiovascular health in African Americans and to highlight unique considerations for disease prevention and management.

Method:
The primary sources of information were identified with PubMed/Medline and online sources from the Centers for Disease Control and Prevention.

Results:
The higher prevalence of traditional cardiovascular risk factors (eg, hypertension, diabetes mellitus, obesity, and atherosclerotic cardiovascular risk) underlies the relatively earlier age of onset of cardiovascular diseases among African Americans. Hypertension in particular is highly prevalent among African Americans and contributes directly to the notable disparities in stroke, heart failure, and peripheral artery disease among African Americans. Despite the availability of effective pharmacotherapies and indications for some tailored pharmacotherapies for African Americans (eg, heart failure medications), disease management is less effective among African Americans, yielding higher mortality. Explanations for these persistent disparities in cardiovascular disease are multifactorial and span from the individual level to the social environment.

Conclusions:
The strategies needed to promote equity in the cardiovascular health of African Americans require input from a broad set of stakeholders, including clinicians and researchers from across multiple disciplines.