bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal diffusion imaging across the C9orf72 clinical spectrum
Authors: Floeter Mary Kay , Danielian Laura E , Braun Laura E , Wu Tianxia 
Published: October 2017

IntroductionDiscrepancies between diffusion tensor imaging (DTI) findings and functional rating scales in amyotrophic lateral sclerosis (ALS) may be due to symptom heterogeneity, particularly coexisting cognitive-behavioural dysfunction affecting non-motor regions of the brain. Carriers of expansion mutations in the C9orf72 gene, whose motor and cognitive-behavioural symptoms span a range from ALS to frontotemporal dementia, present an opportunity to evaluate the relationship between symptom heterogeneity and DTI changes.MethodsTwenty-eight C9orf72 mutation carriers with varied cognitive and motor symptoms underwent clinical evaluation and DTI imaging. Twenty returned for two or more follow-up evaluations. Each evaluation included motor, executive and behavioural scales and disease staging using the King’s college staging system.ResultsWidespread reduction of white matter integrity occurred in C9orf72 mutation carriers compared with 28 controls. The ALS Functional Rating Scale (ALSFRS-R) and King’s stage correlated with DTI measures of the corticospinal tract and mid-callosum. Cognitive and behavioural scores correlated with diffusion measures of frontal white matter. King’s stage, but not ALSFRS-R, correlated with anterior callosum DTI measures. Over a 6-month follow-up, DTI changes spread from anterior to posterior, and from deep to superficial subcortical white matter. In C9orf72 carriers with ALS or ALS-FTD, changes in corticospinal tractography measures correlated with changes in ALSFRS-R.ConclusionDiscrepancies between DTI findings and clinical measures of disease severity in ALS may partly be accounted for by cognitive-behavioural deficits affecting extramotor white matter tracts. Both ALSFRS-R and King’s stage correlated with corticospinal DTI measures. Group-level DTI changes could be detected over 6 months.
Major incident triage and the implementation of a new triage tool, the MPTT-24
Authors: Vassallo James , Smith J E , Wallis L A 
Published: October 2017

IntroductionThe Modified Physiological Triage Tool (MPTT) is a recently developed primary triage tool and in comparison with existing tools demonstrates the greatest sensitivity at predicting need for life-saving intervention (LSI) within both military and civilian populations. To improve its applicability, we proposed to increase the upper respiratory rate (RR) threshold to 24 breaths per minute (bpm) to produce the MPTT-24. Our aim was to conduct a feasibility analysis of the proposed MPTT-24, comparing its performance with the existing UK Military Sieve.MethodA retrospective review of the Joint Theatre Trauma Registry (JTTR) and Trauma Audit Research Network (TARN) databases was performed for all adult (>18 years) patients presenting between 2006–2013 (JTTR) and 2014 (TARN). Patients were defined as priority one (P1) if they received one or more LSIs. Using first recorded hospital RR in isolation, sensitivity and specificity of the ≥24 bpm threshold was compared with the existing threshold (≥22 bpm) at predicting P1 status. Patients were then categorised as P1 or not-P1 by the MPTT, MPTT-24 and the UK Military Sieve.ResultsThe MPTT and MPTT-24 outperformed existing UK methods of triage with a statistically significant (p<0.001) increase in sensitivity of between 25.5% and 29.5%. In both populations, the MPTT-24 demonstrated an absolute reduction in sensitivity with an increase in specificity when compared with the MPTT. A statistically significant difference was observed between the MPTT and MPTT-24 in the way they categorised TARN and JTTR cases as P1 (p<0.001).ConclusionsWhen compared with the existing MPTT, the MPTT-24 allows for a more rapid triage assessment. Both continue to outperform existing methods of primary major incident triage and within the military setting, the slight increase in undertriage is offset by a reduction in overtriage. We recommend that the MPTT-24 be considered as a replacement to the existing UK Military Sieve.
Treatment of recurrent aneurysms using the Woven EndoBridge (WEB): anatomical and clinical results
Authors: Gawlitza Matthias , Soize Sebastien , Januel Anne-Christine , Mihalea Cristian , Metaxas Georgios-Emmanouil , Cognard Christophe , Pierot Laurent 
Published: October 2017

BackgroundThe safety and efficacy of the Woven EndoBridge (WEB) for the treatment of naïve intracranial aneurysms has been confirmed.PurposeTo analyze the safety and efficacy of the WEB in the treatment of recurrent aneurysms.MethodsAnatomical and clinical results in consecutive patients with a recurrent aneurysm, who were treated using the WEB device in two French neurointerventional centers, were evaluated.ResultsSeventeen patients with 17 aneurysms were included. Treatment was feasible in 16 patients. In seven patients (41.2%), ancillary devices were used. Permanent morbidity due to a thromboembolic complication occurred in one patient (5.9%). There was no mortality. Follow-up angiographic studies were available for 15 patients after a mean of 12.1±6.1 months. Rates of complete occlusion, neck remnant, and aneurysm remnant were 33.3%, 40.0%, and 26.7%, respectively.ConclusionsTreatment of recurrent aneurysms using the WEB device may be reasonably safe and effective.
Impact of considering non-occupational radiation exposure on the association between occupational dose and solid cancer among French nuclear workers
Authors: Fournier Lucie , Cléro Enora , Samson Eric , Caër-Lorho Sylvaine , Laurier Dominique , Leuraud Klervi 
Published: October 2017

ObjectivesThe French nuclear worker cohort allows for the assessment of cancer risk associated with occupational radiation exposure, but workers are also exposed to medical and environmental radiation which can be of the same order of magnitude. This study aims to examine the impact of non-occupational radiation exposures on the dose-risk analysis between occupational radiation exposure and cancer mortality.MethodsThe cohort included workers employed before 1995 for at least one year by CEA, AREVA NC or EDF and badge-monitored for external radiation exposure. Monitoring results were used to calculate occupational individual doses. Scenarios of work-related X-ray and environmental exposures were simulated. Poisson regression was used to quantify associations between occupational exposure and cancer mortality adjusting for non-occupational radiation exposure.ResultsThe mean cumulative dose of external occupational radiation was 18.4 mSv among 59 004 workers. Depending on the hypotheses made, the mean cumulative work-related X-ray dose varied between 3.1 and 9.2 mSv and the mean cumulative environmental dose was around 130 mSv. The unadjusted excess relative rate of cancer per Sievert (ERR/Sv) was 0.34 (90% CI −0.44 to 1.24). Adjusting for environmental radiation exposure did not substantially modify this risk coefficient, but it was attenuated by medical exposure (ERR/Sv point estimate between 0.15 and 0.23).ConclusionsOccupational radiation risk estimates were lower when adjusted for work-related X-ray exposures. Environmental exposures had a very slight impact on the occupational exposure risk estimates. In any scenario of non-occupational exposure considered, a positive but insignificant excess cancer risk associated with occupational exposure was observed.
Industrial hog farming is associated with altered circulating immunological markers
Authors: Hofmann Jonathan N , Shiels Meredith S , Friesen Melissa C , Kemp Troy J , Chaturvedi Anil K , Lynch Charles F , Parks Christine G , Pinto Ligia A , Hildesheim Allan , Alavanja Michael C R , Beane Freeman Laura E 
Published: October 2017

ObjectivesThe previously observed inverse association between hog farming and risk of lung cancer in the Agricultural Health Study (AHS) has been attributed to endotoxin exposure, the levels of which are particularly high in industrial hog confinement facilities. We conducted an investigation to explore the potential biological mechanisms underlying this association, as well as other immunological changes associated with hog farming.MethodsSerum immune marker levels were measured using a multiplexed bead-based assay in 61 active hog farmers and 61 controls matched on age, phlebotomy date and raising cattle. Both groups comprised non-smoking male AHS participants from Iowa. We compared natural log-transformed marker levels between hog farmers and controls using multivariate linear regression models.ResultsCirculating levels of macrophage-derived chemokine (CCL22), a chemokine previously implicated in lung carcinogenesis, were reduced among hog farmers (17% decrease; 95% CI −28% to −4%), in particular for those with the largest operations (>6000 hogs: 26% decrease; 95% CI −39% to −10%; ptrend=0.002). We also found that hog farmers had elevated levels of other immune markers, including macrophage inflammatory protein-3 alpha (MIP-3A/CCL20; 111% increase, 95% CI 19% to 273%), basic fibroblast growth factor (FGF-2; 93% increase, 95% CI 10% to 240%) and soluble interleukin-4 receptor (12% increase, 95% CI 1% to 25%), with particularly strong associations for MIP-3A/CCL20 and FGF-2 in winter.ConclusionsThese results provide insights into potential immunomodulatory mechanisms through which endotoxin or other exposures associated with hog farming may influence lung cancer risk, and warrant further investigation with more detailed bioaerosol exposure assessment.
International management platform for children’s interstitial lung disease (chILD-EU)
Authors: Griese Matthias , Seidl Elias , Hengst Meike , Reu Simone , Rock Hans , Anthony Gisela , Kiper Nural , Emiralioğlu Nagehan , Snijders Deborah , Goldbeck Lutz , Leidl Reiner , Ley-Zaporozhan Julia , Krüger-Stollfuss Ingrid , Kammer Birgit , Wesselak Traudl , Eismann Claudia , Schams Andrea , Neuner Doerthe , MacLean Morag , Nicholson Andrew G , Lauren McCann , Clement Annick , Epaud Ralph , de Blic Jacques , Ashworth Michael , Aurora Paul , Calder Alistair , Wetzke Martin , Kappler Matthias , Cunningham Steve , Schwerk Nicolaus , Bush Andy 
Published: October 2017

BackgroundChildren’s interstitial lung diseases (chILD) cover many rare entities, frequently not diagnosed or studied in detail. There is a great need for specialised advice and for internationally agreed subclassification of entities collected in a register.Our objective was to implement an international management platform with independent multidisciplinary review of cases at presentation for long-term follow-up and to test if this would allow for more accurate diagnosis. Also, quality and reproducibility of a diagnostic subclassification system were assessed using a collection of 25 complex chILD cases.MethodsA web-based chILD management platform with a registry and biobank was successfully designed and implemented.ResultsOver a 3-year period, 575 patients were included for observation spanning a wide spectrum of chILD. In 346 patients, multidisciplinary reviews were completed by teams at five international sites (Munich 51%, London 12%, Hannover 31%, Ankara 1% and Paris 5%). In 13%, the diagnosis reached by the referring team was not confirmed by peer review. Among these, the diagnosis initially given was wrong (27%), imprecise (50%) or significant information was added (23%).The ability of nine expert clinicians to subcategorise the final diagnosis into the chILD-EU register classification had an overall exact inter-rater agreement of 59% on first assessment and after training, 64%. Only 10% of the ‘wrong’ answers resulted in allocation to an incorrect category. Subcategorisation proved useful but training is needed for optimal implementation.ConclusionsWe have shown that chILD-EU has generated a platform to help the clinical assessment of chILD.Trial registration numberResults, NCT02852928.
New Generation Nanomedicines Constructed from Self-Assembling Small-Molecule Prodrugs Alleviate Cancer Drug Toxicity
Authors: Wang Hangxiang , Lu Zhongjie , Wang Lijiang , Guo Tingting , Wu Jiaping , Wan Jianqin , Zhou Liqian , Li Hui , Li Zhen , Jiang Donghai , Song Penghong , Xie Haiyang , Zhou Lin , Xu Xiao , Zheng Shusen 
Published: October 2017

Abstract
The therapeutic index for chemotherapeutic drugs is determined in part by systemic toxicity, so strategies for dose intensification to improve efficacy must also address tolerability. In addressing this issue, we have investigated a novel combinatorial strategy of reconstructing a drug molecule and using sequential drug-induced nanoassembly to fabricate supramolecular nanomedicines (SNM). Using cabazitaxel as a target agent, we established that individual synthetic prodrugs tethered with polyunsaturated fatty acids were capable of recapitulating self-assembly behavior independent of exogenous excipients. The resulting SNM could be further refined by PEGylation with amphiphilic copolymers suitable for preclinical studies. Among these cabazitaxel derivatives, docosahexaenoic acid–derived compound 1 retained high antiproliferative activity. SNM assembled with compound 1 displayed an unexpected enhancement of tolerability in animals along with effective therapeutic efficacy in a mouse xenograft model of human cancer, compared with free drug administered in its clinical formulation. Overall, our studies showed how attaching flexible lipid chains to a hydrophobic and highly toxic anticancer drug can convert it to a systemic self-deliverable nanotherapy, preserving its pharmacologic efficacy while improving its safety profile. Cancer Res; 77(24); 6963–74. ©2017 AACR.
Subtype-Specific Tumor-Associated Fibroblasts Contribute to the Pathogenesis of Uterine Leiomyoma
Authors: Wu Xin , Serna Vanida A. , Thomas Justin , Qiang Wenan , Blumenfeld Michael L. , Kurita Takeshi 
Published: October 2017

Abstract
Recent genomic studies have identified subtypes of uterine leiomyoma (LM) with distinctive genetic alterations. Here, we report the elucidation of the biological characteristics of the two most prevalent uterine leiomyoma subtypes, MED12-mutant (MED12-LM) and HMGA2-overexpressing (HMGA2-LM) uterine leiomyomas. Because each tumor carries only one genetic alteration, both subtypes are considered to be monoclonal. Approximately 90% of cells in HMGA2-uterine leiomyoma were smooth muscle cells (SMC) with HMGA2 overexpression. In contrast, MED12-LM consisted of similar numbers of SMC and non-SMC, which were mostly tumor-associated fibroblasts (TAF). Paradoxically, TAF carried no mutations in MED12, suggesting an interaction between SMC and TAF to coordinate their growth. The higher amount of extracellular matrix in MED12-LM than HMGA2-LM was partially due to the high concentration of collagen-producing TAF. SMC growth in a xenograft assay was driven by progesterone in both uterine leiomyoma subtypes. In contrast, TAF in MED12-LM proliferated in response to estradiol, whereas progesterone had no effect. The high concentration of estrogen-responsive TAF in MED12-LM explains the inconsistent discoveries between in vivo and in vitro studies on the mitogenic effect of estrogen and raises questions regarding the accuracy of previous studies utilizing MED12-LM cell culture. In addition, the differential effects of estradiol and progesterone on these uterine leiomyoma subtypes emphasize the importance of subtypes and genotypes in designing nonsurgical therapeutic strategies for uterine leiomyoma. Cancer Res; 77(24); 6891–901. ©2017 AACR.
Breast Cancer in Latinas: A Focus on Intrinsic Subtypes Distribution
Authors: Serrano-Gómez Silvia J. , Fejerman Laura , Zabaleta Jovanny 
Published: October 2017

Abstract
Breast cancer is the most frequent cancer in women worldwide. It is classified into intrinsic subtypes characterized by different molecular profiles and prognosis. The prevalence of the different intrinsic subtypes varies between population groups. IHC surrogates based on the expression of the estrogen receptor, progesterone receptor, and HER2 have been widely used to study the distribution of intrinsic subtypes in non-Hispanic whites and African Americans, but data are limited for Hispanic/Latina women. Similarly, most studies analyzing gene expression profiles only include women of European descent. This review focuses on studies that describe the distribution of breast cancer subtypes in Hispanic/Latina women and highlights the need for more research in this population. Cancer Epidemiol Biomarkers Prev; 27(1); 3–10. ©2017 AACR.
Phase I Study of Enavatuzumab, a First-in-Class Humanized Monoclonal Antibody Targeting the TWEAK Receptor, in Patients with Advanced Solid Tumors
Authors: Lam Elaine T. , Eckhardt S. Gail , Messersmith Wells , Jimeno Antonio , O'Bryant Cindy L. , Ramanathan Ramesh K. , Weiss Glen J. , Chadha Manpreet , Oey Abbie , Ding Han Ting , Culp Patricia A. , Keller Stephan F. , Zhao Vivian Y. , Tsao L. Claire , Singhal Anil , Holen Kyle D. , Von Hoff Daniel 
Published: October 2017

AbstractThis phase I study evaluates the safety, MTD, pharmacokinetics (PK), pharmacodynamics, and preliminary anticancer activity of enavatuzumab, a humanized IgG1 antibody to the TWEAK receptor, in patients with advanced solid malignancies. Patients received escalating doses of enavatuzumab given intravenously over 60 minutes every 2 weeks. Blood was obtained for PK and biomarker assessment. Three patients were enrolled per dose level in a standard 3+3 design with response assessment by RECIST version 1.0, every 8 weeks. Thirty patients were enrolled at 6 dose levels ranging from 0.1 to 1.5 mg/kg. Dose-limiting toxicities included grade 4 (G4) lipase, G3 bilirubin, and G4 amylase elevations. There was no apparent correlation of liver or pancreatic enzyme elevation with drug exposure or the presence of liver metastases. Enavatuzumab exhibited a two-compartment linear PK model. Estimated systemic clearance was 23 to 33 mL/h with an elimination half-life of 7 to 18 days. The predicted target efficacious peak and trough concentrations occurred at 1.0 mg/kg following the second dose. There were no objective responses; 4 patients had stable disease. The MTD of enavatuzumab is 1.0 mg/kg i.v. every 2 weeks. Higher doses were not tolerated due to hepatopancreatic lab abnormalities. Further evaluation of the mechanisms of the liver and pancreatic enzyme toxicities is needed before embarking on further single-agent or combination strategies. Mol Cancer Ther; 17(1); 215–21. ©2017 AACR.
Acute Biventricular Mechanical Circulatory Support for Cardiogenic Shock
Authors: Kuchibhotla Sudeep , Esposito Michele L. , Breton Catalina , Pedicini Robert , Mullin Andrew , O'Kelly Ryan , Anderson Mark , Morris Dennis L. , Batsides George , Ramzy Danny , Grise Mark , Pham Duc Thinh , Kapur Navin K. 
Published: October 2017

Background
Biventricular failure is associated with high in‐hospital mortality. Limited data regarding the efficacy of biventricular Impella axial flow catheters (BiPella) support for biventricular failure exist. The aim of this study was to explore the clinical utility of percutaneously delivered BiPella as a novel acute mechanical support strategy for patients with cardiogenic shock complicated by biventricular failure.

Methods and Results

We retrospectively analyzed data from 20 patients receiving BiPella for biventricular failure from 5 tertiary‐care hospitals in the United States. Left ventricular support was achieved with an Impella 5.0 (n=8), Impella
CP
(n=11), or Impella 2.5 (n=1). All patients received the Impella
RP
for right ventricular (
RV
) support. BiPella use was recorded in the setting of acute myocardial infarction (n=11), advanced heart failure (n=7), and myocarditis (n=2). Mean flows achieved were 3.4±1.2 and 3.5±0.5 for left ventricular and
RV
devices, respectively. Total in‐hospital mortality was 50%. No intraprocedural mortality was observed. Major complications included limb ischemia (n=1), hemolysis (n=6), and Thrombolysis in Myocardial Infarction major bleeding (n=7). Compared with nonsurvivors, survivors were younger, had a lower number of inotropes or vasopressors used before BiPella, and were more likely to have both devices implanted simultaneously during the same procedure. Compared with nonsurvivors, survivors had lower pulmonary artery pressures and
RV
stroke work index before BiPella. Indices of
RV
afterload were quantified for 14 subjects. Among these patients, nonsurvivors had higher pulmonary vascular resistance (6.8; 95% confidence interval [95%
CI
], 5.5–8.1 versus 1.9; 95%
CI
, 0.8–3.0;
P
<0.01), effective pulmonary artery elastance (1129; 95%
CI
, 876–1383 versus 458; 95%
CI
, 263–653;
P
<0.01), and lower pulmonary artery compliance (1.5; 95%
CI
, 0.9–2.1 versus 2.7; 95%
CI
, 1.8–3.6;
P
<0.05).

Conclusions

This is the largest, retrospective analysis of BiPella for cardiogenic shock. BiPella is feasible, reduces cardiac filling pressures and improves cardiac output across a range of causes for cardiogenic shock. Simultaneous left ventricular and
RV
device implantation and lower
RV
afterload may be associated with better outcomes with BiPella. Future prospective studies of BiPella for cardiogenic shock are required.
Soil nematode abundance and diversity from four vegetation types in Central Mexico
Authors: Mejía-Madrid Hugo H. 
Published: October 2017

Soil nematode abundance and MOTU diversity were estimated from a geographically broad area of Mexico that included four out of seven recognised vegetation types. Vegetation types were assessed for abundance and diversity of nematode communities and inferred ecological relationships between them. Soils were sampled from tropical rainforest, tropical dry deciduous forest, temperate coniferous forest and xerophytic shrub during 2013, 2014 and 2015. Fourteen sampling sites withca10-20 samples per site from 11 localities spread across Central Mexico were assessed. Altitudes sampled ranged from 113 m a.s.l. (tropical coastal plain) to 2400 m a.s.l. (Trans-Mexican Volcanic Belt). Samples were drawn from conserved and cultivated plots from each sampling site covering an area of ⩾100 m2. A total of 13 263 individuals from 25 identified families of nematodes were collected. Family abundance and complementarity indices between sites revealed to some extent the affinities between vegetation types. Nevertheless, statistical analyses revealed no differences between nematode family abundances between sites, only between families across all sites. Molecular operational taxonomic units (MOTU) methods were employed as a framework to assess biodiversity. From these, 77 high-quality sequences for taxonomic barcoding were recovered and later identified with morphological traits. Only six sequences matched at a 98-99% level with those reported in GenBank. Sequences amounted to a total of 41 MOTU, where 100% of the MOTU from both conserved and disturbed tropical rainforest, tropical dry deciduous forest and xerophytic shrub exhibited a ⩾3% cut-off genetic identity, whilst temperate coniferous forest and disturbed temperate coniferous forest showed 73% and 70% respectively. In addition, 12.2% MOTU were shared among localities and 87.8% exhibited an apparently locality-limited distribution. The potential for a considerable diversity of nematodes, as revealed from a small sample of MOTU diversity, is discussed.