bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liquid biopsies to track trastuzumab resistance in metastatic HER2-positive gastric cancer
Authors: Wang De-Shen , Liu Ze-Xian , Lu Yun-Xin , Bao Hua , Wu Xue , Zeng Zhao-Lei , Liu Zekun , Zhao Qi , He Cai-Yun , Lu Jia-Huan , Wang Zhi-Qiang , Qiu Miao-Zhen , Wang Feng , Wang Feng-Hua , Li Yu-Hong , Wang Xiao-Nan , Xie Dan , Jia Wei-Hua , Shao Yang W , Xu Rui-Hua 
Published: September 2018

ObjectiveTo monitor trastuzumab resistance and determine the underlying mechanisms for the limited response rate and rapid emergence of resistance of HER2+ metastatic gastric cancer (mGC).DesignTargeted sequencing of 416 clinically relevant genes was performed in 78 paired plasma and tissue biopsy samples to determine plasma-tissue concordance. Then, we performed longitudinal analyses of 97 serial plasma samples collected from 24 patients who were HER2+  to track the resistance during trastuzumab treatment and validated the identified candidate resistance genes.ResultsThe results from targeted sequencing-based detection of somatic copy number alterations (SCNA) of HER2 gene were highly consistent with fluorescence in situ hybridisation data, and the detected HER2 SCNA was better than plasma carcinoembryonic antigen levels at predicting tumour shrinkage and progression. Furthermore, most patients with innate trastuzumab resistance presented high HER2 SCNA during progression compared with baseline, while HER2 SCNA decreased in patients with acquired resistance. PIK3CA mutations were significantly enriched in patients with innate resistance, and ERBB2/4 genes were the most mutated genes, accounting for trastuzumab resistance in six (35.3%) and five (29.4%) patients in baseline and progression plasma, respectively. Patients with PIK3CA/R1/C3 or ERBB2/4 mutations in the baseline plasma had significantly worse progression-free survival. Additionally, mutations in NF1 contributed to trastuzumab resistance, which was further confirmed through in vitro and in vivo studies, while combined HER2 and MEK/ERK blockade overcame trastuzumab resistance.ConclusionLongitudinal circulating tumour DNA sequencing provides novel insights into gene alterations underlying trastuzumab resistance in HER2+mGC.
Anaesthetic management during intracranial mechanical thrombectomy: systematic review and meta-analysis of current data
Authors: Gravel Guillaume , Boulouis Grégoire , Benhassen Wagih , Rodriguez-Regent Christine , Trystram Denis , Edjlali-Goujon Myriam , Meder Jean-François , Oppenheim Catherine , Bracard Serge , Brinjikji Waleed , Naggara Olivier N 
Published: September 2018

ObjectiveOur aim was to compare the clinical outcome of patients with ischaemic stroke with anterior large vessel occlusion treated with stent retrievers and/or contact aspiration mechanical thrombectomy (MT) under general anaesthesia (GA) or conscious sedation non-GA through a systematic review and meta-analysis.MethodsThe literature was searched using PubMed, Embase and Cochrane databases to identify studies reporting on anaesthesia and MT. Using fixed or random weighted effect, we evaluated the following outcomes: 3-month mortality, modified Rankin Score (mRs) 0–2, recanalisation success (thrombolysis in cerebral infarction (TICI) ≥2b) and symptomatic intracerebral haemorrhagic (sICH) transformation.ResultsWe identified seven cohorts (including three dedicated randomised controlled trials), totalling 1929 patients (932 with GA). Over the entire sample, mortality, mRs 0–2, TICI≥2b and sICH rates were, respectively 17.5% (99% CI 9.7% to 29.6%; Q-value: 60.1; I2: 93%, 1717 patients), 42.1% (99% CI 33.3% to 51.7%; Q-value: 41.3; I2: 87.9%), 82.9% (99% CI 74.0% to 89.1%; Q-value: 20.7; I2: 80.6%, 1006 patients) and 5.5% (99% CI 2.8% to 10.8%; Q-value: 18.6; I2: 78.5%). MT performed in non-GA patients was associated with better 3-month functional outcome (pooled OR, 1.35; 99% CI 1.04 to 1.76; Q-value: 24.0; I2: 9.2%, 1845 patients) and lower 3-month mortality rate (pooled OR, 0.70; 99% CI 0.49 to 0.98; Q-value: 1.4; I2: 0%, 1717 patients; fixed weighted effect model) compared with GA. MT performed under conscious sedation non-GA had significantly shorter onset-to-recanalisation and onset-to-groin delay compared with GA, and recanalisation success and sICH were similar.ConclusionNon-GA during MT for anterior acute ischaemic stroke with current-generation stent retriever/aspiration devices is associated with better 3-month functional outcome and lower mortality rates. These unadjusted estimates are subject to biases and should be interpreted with caution.
Single-center experience with the Tigertriever device for the recanalization of large vessel occlusions in acute ischemic stroke
Authors: Kara Batuhan , Selcuk Hatem Hakan , Erbahceci Salik Aysun , Zalov Hasanagha , Yildiz Omer , Gul Gunay , Balkan Bedih 
Published: September 2018

BackgroundTigertriever (Rapid Medical, Yoqneam, Israel) is a new design of stent retriever.PurposeTo evaluate the feasibility, safety, and efficacy of the Tigertriever in patients with acute ischemic stroke who have undergone mechanical thrombectomy.Materials and methodsTwo different techniques—namely, standard unsheathing (SUT) and repetitive inflation-deflation (RID) techniques, were used. Modified Thrombolysis in Cerebral Infarction (mTICI) scores of 2b and 3 were considered as successful recanalization.ResultsA total of 61 thrombectomy procedures with Tigertriever were retrospectively evaluated. The mean age of patients was 60.7 years and their National Institutes of Health Stroke Scale score was 14.7. Overall, the percentage of patients with a mTICI score of 0, 2b, and 3 was 24.6, 26.2, and 49.2, respectively. Successful recanalization and first-pass success rates were 75.4% and 37.7%, respectively. There were no statistical differences between the results of the SUT and RID techniques. No vessel rupture, dissection, or device detachment was observed. The number of patients with a good clinical outcome (modified Rankin Scale score 0–2) was 17 (27.9%).ConclusionOur results showed that the Tigertriever device is safe and efficient for mechanical thrombectomy.
Assessment of reclaimed soils by unsupervised clustering of proximal sensor data
Authors: Sorenson P.T. , Small C. , Quideau S.A. , Underwood A. , Janz A. 
Published: September 2018

The application of soil proximal sensors on reclaimed sites presents a novel method for assessing the quality of reclaimed landscapes. This method improves assessment reliability, information management, and environmental assurance. One proximal sensing system that could be used to provide high spatial resolution measurements of soil parameters is an on-the-go optical sensor that collects data at two wavelengths: 660 and 940 nm. Proximal soil sensing data were collected at 27 sites, where organic matter, cation exchange capacity (CEC), and soil water content were collected from 221 soil samples from 0 to 15 cm. The proximal soil sensor data were then automatically clustered using a combination of self-organizing maps and random uniform forests. Overall, the proximal sensor data combined with this data analysis approach created maps with either three or four soil zones. On average, soil zones had statistically significant differences in organic matter, CEC, and water content. This system could be used to map out zones with significant soil variation as part of reclamation monitoring and then used to guide laboratory analytical sampling. Future work should focus on development of on-the-go reflectance spectroscopy systems to provide quantitative soil data with high spatial resolution.
CBP Modulates Sensitivity to Dasatinib in Pre-BCR+ Acute Lymphoblastic Leukemia
Authors: Duque-Afonso Jesús , Lin Chiou-Hong , Han Kyuho , Morgens David W. , Jeng Edwin E. , Weng Ziming , Jeong Johan , Wong Stephen Hon Kit , Zhu Li , Wei Michael C. , Chae Hee-Don , Schrappe Martin , Cario Gunnar , Duyster Justus , Xiao Xiangshu , Sakamoto Kathleen M. , Bassik Michael C. , Cleary Michael L. 
Published: September 2018

Abstract
Dasatinib is a multi-tyrosine kinase inhibitor approved for treatment of Ph+ acute lymphoblastic leukemia (ALL), but its efficacy is limited by resistance. Recent preclinical studies suggest that dasatinib may be a candidate therapy in additional ALL subtypes including pre-BCR+ ALL. Here we utilized shRNA library screening and global transcriptomic analysis to identify several novel genes and pathways that may enhance dasatinib efficacy or mitigate potential resistance in human pre-BCR+ ALL. Depletion of the transcriptional coactivator CBP increased dasatinib sensitivity by downregulating transcription of the pre-BCR signaling pathway previously associated with dasatinib sensitivity. Acquired resistance was due, in part, to upregulation of alternative pathways including WNT through a mechanism, suggesting transcriptional plasticity. Small molecules that disrupt CBP interactions with the CREB KID domain or β-catenin showed promising preclinical efficacy in combination with dasatinib. These findings highlight novel modulators of sensitivity to targeted therapies in human pre-BCR+ ALL, which can be reversed by small-molecule inhibitors. They also identify promising therapeutic approaches to ameliorate dasatinib sensitivity and prevent resistance in ALL.
Significance: These findings reveal mechanisms that modulate sensitivity to dasatinib and suggest therapeutic strategies to improve the outcome of patients with acute lymphoblastic leukemia.
Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/22/6497/F1.large.jpg. Cancer Res; 78(22); 6497–508. ©2018 AACR.
Prediagnostic Serum Levels of Fatty Acid Metabolites and Risk of Ovarian Cancer in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial
Authors: Hada Manila , Edin Matthew L. , Hartge Patricia , Lih Fred B. , Wentzensen Nicolas , Zeldin Darryl C. , Trabert Britton 
Published: September 2018

Abstract

Background:
Evidence suggests that inflammation increases risk for ovarian cancer. Aspirin has been shown to decrease ovarian cancer risk, though the mechanism is unknown. Studies of inflammatory markers, lipid molecules such as arachidonic acid, linoleic acid, and alpha-linoleic acid metabolites, and development of ovarian cancer are essential to understand the potential mechanisms.

Methods:
We conducted a nested case–control study (157 cases/156 matched controls) within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Unconditional logistic regression was used to estimate the association between prediagnostic serum levels of 31 arachidonic acid/linoleic acid/alpha-linoleic acid metabolites and risk of ovarian cancer.

Results:
Five of the 31 arachidonic acid/linoleic acid/alpha-linoleic acid (free fatty acids) metabolites were positively associated with ovarian cancer risk: 8-HETE [tertile 3 vs. 1: OR 2.53 (95% confidence interval [CI] 1.18–5.39), Ptrend 0.02], 12,13-DHOME [2.49 (1.29–4.81), 0.01], 13-HODE [2.47 (1.32–4.60), 0.005], 9-HODE [1.97 (1.06–3.68), 0.03], 9,12,13-THOME [2.25 (1.20–4.21), 0.01]. In analyses by subtype, heterogeneity was suggested for 8-HETE [serous OR (95% CI): 2.53 (1.18–5.39) vs. nonserous OR (95% CI): 1.15 (0.56–2.36), Phet 0.1] and 12,13-EpOME [1.95 (0.90–4.22) vs. 0.82 (0.39–1.73), 0.05].

Conclusions:
Women with increased levels of five fatty acid metabolites (8-HETE, 12,13-DHOME, 13-HODE, 9-HODE, and 9,12,13-THOME) were at increased risk of developing ovarian cancer in the ensuing decade. All five metabolites are derived from either arachidonic acid (8-HETE) or linoleic acid (12,13-DHOME, 13-HODE, 9-HODE, 9,12,13-THOME) via metabolism through the LOX/cytochrome P450 pathway.

Impact:
The identification of these risk-related fatty acid metabolites provides mechanistic insights into the etiology of ovarian cancer and indicates the direction for future research.
Causes of Inferior Outcome in Adolescents and Young Adults with Acute Lymphoblastic Leukemia: Across Oncology Services and Regardless of Clinical Trial Enrollment
Authors: Wolfson Julie A. , Richman Joshua S. , Sun Can-Lan , Landier Wendy , Leung Karen , Smith Eileen P. , O’Donnell Margaret , Bhatia Smita 
Published: September 2018

Abstract
Background: Adolescents and young adults (AYA: 15–39 years) with acute lymphoblastic leukemia (ALL) have inferior survival when compared with children (1–14 years). An approach is lacking that includes both patients enrolled and not enrolled in clinical trials, and includes the contribution of health care delivery, treatment, and clinical prognosticators.
Methods: We assembled a retrospective cohort of ALL patients diagnosed between 1–39 years (AYA: n = 93; child: n = 91) and treated at a single institution between 1990 and 2010, irrespective of clinical trial enrollment. We modeled relapse risk (i) during therapy and (ii) after completing therapy.
Results: On-therapy relapse: AYA experienced an increased risk of on-therapy relapse versus children (HR, 10.5; P = 0.004). In multivariable analysis restricted to AYA, independent predictors of relapse included lack of clinical trial enrollment (HR, 2.6, P = 0.04) and nonwhite race/ethnicity (HR, 2.2; P = 0.05). Relapse after completing therapy: When compared with children, AYA experienced an increased risk of relapse after completing therapy (HR, 7.7; P &lt; 0.001). In multivariable analysis restricted to AYA, longer therapy (months of maintenance: HR, 0.7; P &lt; 0.001; months of consolidation: HR, 0.8; P = 0.03) protected against relapse.
Conclusions: Among AYA, aspects of health care delivery (clinical trial enrollment, nonwhite race/ethnicity) are associated with relapse during therapy, and aspects of treatment (shorter duration of maintenance and consolidation) are associated with relapse after completing therapy.
Impact: These findings highlight the importance of clinical trial enrollment and therapy duration (maintenance, consolidation) in ensuring durable remissions in AYA ALL. Future studies encompassing health care delivery, treatment, and biology are needed. Cancer Epidemiol Biomarkers Prev; 27(10); 1133–41. ©2018 AACR.
ВПЛИВ ВІРУСНОГО НАВАНТАЖЕННЯ ВІРУСОМ ІМУНОДЕФІЦИТУ ЛЮДИНИ НА ВИЖИВАННЯ ХВОРИХ ІЗ ВІЛ-ІНФЕКЦІЄЮ ПРОТЯГОМ 5 РОКІВ СПОСТЕРЕЖЕННЯ
Authors: Shevelоva O. V. , Shostakovych-Koretskaya L. R. , Lytvyn K. Yu. 
Published: September 2018

Мета: на основі 5-річного спостереження ВІЛ-інфікованих хворих, яким було призначено ВААРТ, оцінити вплив вірусного навантаження ВІЛ РНК та СD4+ на початку високоактивної антиретровірусної терапії на смертність пацієнтів.Матеріали і методи. Аналіз хворих проводили з урахуванням клінічних і лабораторних показників. Використовували описову статистику кількісних даних у групах; кореляційний аналіз.Результати. Всі хворі отримували високоактивну антиретровірусну терапію не менше 5 років. Імунофено­типування периферійної крові показало такі результати: медіана (Ме, 25–75 процентиль) рівня CD4+ склала 186 (90–262) копій/мл, вірусне навантаження – 75,358 (19,091–326,273) ВІЛ РНК копій/мл. За 5 років спостереження померли 63 пацієнти. Найбільший відсоток хворих на ВІЛ-інфекцію померли у перші 12 місяців лікування і склали 58,73 %. Протягом наступних двох років проведення лікування щорічно померли 11,11 та 14,28 % відповідно. На четвертому році після початку ВААРТ померли 11,11 % хворих. За 5 рік проведення ВААРТ померли 4,76 % хворих.Висновки. У ВІЛ-інфікованих хворих, яким було призначено ВААРТ, визначено зв’язок між кількістю Т-лімфоцитів-хелперів та вірусним навантаженням (rs=-0,821; р=0,000) у період 5-річного спостереження. Найбільший нако­пи­чений ризик смерті – 0,1, виявлено у групах пацієнтів із більшим ступенем імуносупресії.
АНАЛІЗ СМЕРТНОСТІ НАСЕЛЕННЯ УКРАЇНИ ВНАСЛІДОК НАВМИСНОГО САМОУШКОДЖЕННЯ
Authors: Slabkiy G. O. , Zashchik N. S. 
Published: September 2018

Мета: вивчити і проаналізувати дані про смертність населення в регіональному аспекті внаслідок навмисного самоушкодження за місцем проживання, статтю і способом позбавлення життя.Матеріали і методи. Під час виконання цього дослідження використано дані Державного комітету статистики України за 2014 р. Методом дослідження є статистичний метод.Результати. Показники смертності населення внаслідок навмисного самоушкодження в розрахунку на 100 000 насе­лення складають серед всього населення України – 18,403, серед міських жителів – 13,621, серед сільських жителів – 27,459, серед чоловіків – 31,985, серед жінок – 23,385. Показники мають достовірні відмінності по регіонах країни.Висновки. Високий рівень смертності населення внаслідок навмисного самоушкодження потребує розробки в рамках системи громадського здоров'я, міжсекторальної програми її профілактики.
Estrogen Inhibits LDL (Low-Density Lipoprotein) Transcytosis by Human Coronary Artery Endothelial Cells via GPER (G-Protein–Coupled Estrogen Receptor) and SR-BI (Scavenger Receptor Class B Type 1)
Authors: Ghaffari Siavash , Naderi Nabi Farnoosh , Sugiyama Michael G. , Lee Warren L. 
Published: September 2018

Objective—
The atheroprotective effects of estrogen are independent of circulating lipid levels. Whether estrogen regulates transcytosis of LDL (low-density lipoprotein) across the coronary endothelium is unknown.

Approach and Results—
Using total internal reflection fluorescence microscopy, we quantified transcytosis of LDL across human coronary artery endothelial cells from multiple donors. LDL transcytosis was significantly higher in cells from men compared with premenopausal women. Estrogen significantly attenuated LDL transcytosis by endothelial cells from male but not female donors; transcytosis of albumin was not affected. Estrogen caused downregulation of endothelial SR-BI (scavenger receptor class B type 1), and overexpression of SR-BI was sufficient to restore LDL transcytosis. Similarly, depletion of SR-BI by siRNA attenuated endothelial LDL transcytosis and prevented any further effect of estrogen. In contrast, treatment with estrogen had no effect on SR-BI expression by liver cells. Inhibition of estrogen receptors α and β had no effect on estrogen-mediated attenuation of LDL transcytosis. However, estrogen’s effect on LDL transcytosis was blocked by depletion of the GPER (G-protein–coupled estrogen receptor). GPER was found to be enriched in endothelial cells compared with hepatocytes and is reported to signal via transactivation of the EGFR (epidermal growth factor receptor); inhibition of EGFR prevented the effect of estrogen on LDL transcytosis and SR-BI mRNA. Last, SR-BI expression was significantly higher in human coronary artery endothelial cells from male compared with premenopausal female donors.

Conclusions—
Estrogen significantly inhibits LDL transcytosis by downregulating endothelial SR-BI; this effect requires GPER.
Shallow-to-Deep Transition of Continental Moist Convection: Cold Pools, Surface Fluxes, and Mesoscale Organization
Authors: Kurowski Marcin J. , Suselj Kay , Grabowski Wojciech W. , Teixeira Joao 
Published: September 2018

Abstract
Large-eddy simulation is used to investigate the effects of cold pools driven by rain evaporation on the shallow-to-deep convection transition over land. The physically consistent methodologies are developed to obtain a time-dependent reference ensemble without cold pools and to apply interactive surface heat fluxes without modeling of surface energy and water budgets. Three different simulation ensembles are contrasted. The reference ensemble, in the spirit of one-dimensional single-column models, eliminates cold pools by horizontally homogenizing negative buoyancy production due to rain evaporation. The additional ensembles complement the reference cold-pool-free ensemble by including cold pools and by applying either interactive or prescribed surface fluxes. Contrasting these ensembles suggests possible improvements of convection parameterization in large-scale models of weather and climate. Without cold pools, the reference ensemble preserves key features of buoyancy-driven cellular convection associated with a field of convective plumes, as assumed in a typical convection parameterization. With cold pools, a significant enhancement of surface heat and moisture fluxes and about an hour delay of their daily maximum is simulated. Cold pools enhance near-surface temperature and moisture standard deviations as well as maxima of the near-surface updraft velocity. They also lead to the reduction of cloud lateral entrainment, deeper vertical development of the cloud layer, and a few-times-larger accumulated surface precipitation. Interactive surface fluxes provide a damping mechanism that noticeably suppresses all these effects. Perhaps surprisingly, cold pools do not significantly change the cloud-base convective mass flux that approximately follows the evolution of surface heat fluxes.
The Wire Flyer Towed Profiling System
Authors: Roman Chris , Ullman David S. , Hebert Dave , Licht Stephen 
Published: September 2018

Abstract
The Wire Flyer towed vehicle is a new platform able to collect high-resolution water column sections. The vehicle is motivated by a desire to effectively capture spatial structures at the submesoscale. The vehicle fills a niche that is not achieved by other existing towed and repeat profiling systems. The Wire Flyer profiles up and down along a ship-towed cable autonomously using controllable wings for propulsion. At ship speeds between 2 and 5 kt (1.02–2.55 m s−1), the vehicle is able to profile over prescribed depth bands down to 1000 m. The vehicle carries sensors for conductivity, temperature, depth, oxygen, turbidity, chlorophyll, pH, and oxidation reduction potential. During normal operations the vehicle is typically commanded to cover vertical regions between 300 and 400 m in height with profiles that repeat at kilometer spacing. The vertical profiling speed can be user specified up to 150 m min−1. The high-density sampling capability at depths below the upper few hundred meters makes the vehicle distinct from other systems. During operations an acoustic modem is used to communicate with the vehicle to provide status information, data samples, and the ability to modify the sampling pattern. This paper provides an overview of the vehicle system, describes its operation, and presents results from several cruises.
National comparative audit of red blood cell transfusion practice in hospices: Recommendations for palliative care practice
Authors: Neoh Karen , Gray Ross , Grant-Casey John , Estcourt Lise , Malia Catherine , Boland Jason W , Bennett Michael I 
Published: September 2018

Background: Red blood cell transfusions are commonly used in palliative care to treat anaemia or symptoms caused by anaemia. In patients with advanced disease, there is little evidence of benefit to guide treatment decisions in the face of increased risk of harms. Aim: To determine national transfusion practice in hospices and compare this against National Institute for Health and Care Excellence and British Society of Haematology guidelines to develop recommendations to improve practice. Design and Setting: Prospective data collection on red blood cell transfusion practice in UK adult hospices over a 3-month census period. Results: A total of 121/210 (58%) hospices participated. A total of 465 transfusion episodes occurred in 83 hospices. Patients had a mean age of 71 years, and 96% had cancer. Mean pre-transfusion haemoglobin was 75 g/L (standard deviation = 11.15). Anaemia of chronic disease was the largest cause of anaemia (176; 38%); potentially amenable to alternative treatments. Haematinics were not checked in 70% of patients. Alternative treatments such as B12, folate and iron were rarely used. Despite transfusion-associated circulatory overload risk, 85% of patients were not weighed, and 84% had two or more units transfused. Only 83 (18%) patients had an improvement maintained at 30 days; 142 (31%) had <14 day improvement, and 50 (11%) had no improvement. A total of 150 patients (32%) were dead at 30 days. Conclusion: More rigorous investigation of anaemia, increased use of alternative therapies and more restrictive approach to red cell transfusions are recommended. Clinicians should discuss the limited benefit versus potentially higher risks with patients in hospice services to inform treatment decisions.