bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dissemination of results from medical student public health research training and factors associated with publication
Authors: Al-Busaidi Ibrahim Saleh , Tarr Gregory Patrick 
Published: March 2018

AbstractPurposeTo examine factors associated with successful publications resulting from mandatory public health research training attachment, the Trainee Intern Health Care Evaluation (TIHE) projects, at the University of Otago, Dunedin School of Medicine, New Zealand.MethodsA total of 227 TIHE projects completed during the period from January 1985 to December 2013 were included in the study. In February 2016, Medline and Google Scholar databases were searched independently by both authors for publications using predefined search criteria.ResultsOverall, 25 (11.1%) out of 227 projects resulted in 19 articles, 3 conference presentations/abstracts and 4 cited report abstracts. Nineteen (8.4%) projects resulted in 22 peer-reviewed journal publications, the majority of which were original articles (86.4%). The number of projects commissioned by a client was independently associated with the likelihood of publication, conference abstract or citation of the project report (OR 1.40; P&lt;0.01, 95% CI 1.14 to 1.71). The number of authors and the number of non-student authors were positively associated with publication in higher impact journals, while student first-authored articles were more likely to be published in lower impact journals. Projects completed in more recent years were more likely to be published.ConclusionsMandatory medical student research experiences promote tangible research output. These findings may help to influence policy around the introduction of required medical school research and facilitate encouraging academic careers among medical students. Future research could focus on examining how different student-related, supervisor-related and programme-related factors influence publication rates from mandatory medical student research attachments.
Structural development of the northern Dutch offshore: Paleozoic to present
Authors: ter Borgh M. M. , Jaarsma B. , Rosendaal E. A. 
Published: March 2018

Abstract
We used new high-quality 2D and 3D seismic data covering the northern Dutch offshore to develop a structural framework for Paleozoic–recent times. Early Carboniferous extension was accommodated predominantly along WNW–ESE-trending faults, and was characterized by an alternation of highs and lows; in the northern Dutch offshore, the principal high coincides with the present-day Elbow Spit Platform. An Early Carboniferous low, the North Elbow Basin, is present north of this high in the A and B quadrants. Lower Carboniferous deposits have been preserved here and on the Elbow Spit Platform. Late Carboniferous–Early Rotliegend deformation is accommodated primarily along normal faults with a NE–SW trend. These faults commonly show no significant offset of Upper Rotliegend and younger units. Development of the Dutch Central Graben and Step Graben occurred during the Triassic–Early Cretaceous, primarily along north–south-trending faults, but reactivation of pre-existing faults as oblique-slip faults occurred as well. Associated with these north–south-trending faults was another, not previously described, family of WSW–ENE-trending dextral strike-slip faults which are proposed to represent transfer faults that accommodated strain partitioning.
Cotargeting BCL-2 and PI3K Induces BAX-Dependent Mitochondrial Apoptosis in AML Cells
Authors: Rahmani Mohamed , Nkwocha Jewel , Hawkins Elisa , Pei Xinyan , Parker Rebecca E. , Kmieciak Maciej , Leverson Joel D. , Sampath Deepak , Ferreira-Gonzalez Andrea , Grant Steven 
Published: March 2018

Abstract
Inhibitors targeting BCL-2 apoptotic proteins have significant potential for the treatment of acute myeloid leukemia (AML); however, complete responses are observed in only 20% of patients, suggesting that targeting BCL-2 alone is insufficient to yield durable responses. Here, we assessed the efficacy of coadministration of the PI3K/mTOR inhibitor GDC-0980 or the p110β-sparing PI3K inhibitor taselisib with the selective BCL-2 antagonist venetoclax in AML cells. Tetracycline-inducible downregulation of BCL-2 significantly sensitized MV4-11 and MOLM-13 AML cells to PI3K inhibition. Venetoclax/GDC-0980 coadministration induced rapid and pronounced BAX mitochondrial translocation, cytochrome c release, and apoptosis in various AML cell lines in association with AKT/mTOR inactivation and MCL-1 downregulation; ectopic expression of MCL-1 significantly protected cells from this regimen. Combined treatment was also effective against primary AML blasts from 17 patients, including those bearing various genetic abnormalities. Venetoclax/GDC-0980 markedly induced apoptosis in primitive CD34+/38−/123+ AML cell populations but not in normal hematopoietic progenitor CD34+ cells. The regimen was also active against AML cells displaying intrinsic or acquired venetoclax resistance or tumor microenvironment–associated resistance. Either combinatorial treatment markedly reduced AML growth and prolonged survival in a systemic AML xenograft mouse model and diminished AML growth in two patient-derived xenograft models. Venetoclax/GDC-0980 activity was partially diminished in BAK−/− cells and failed to induce apoptosis in BAX−/− and BAX−/−BAK−/− cells, whereas BIM−/− cells were fully sensitive. Similar results were observed with venetoclax alone in in vitro and in vivo systemic xenograft models. Collectively, these studies demonstrate that venetoclax/GDC-0980 exhibits potent anti-AML activity primarily through BAX and, to a lesser extent, BAK. These findings argue that dual BCL-2 and PI3K inhibition warrants further evaluation in AML.
Significance: Combined treatment with clinically relevant PI3K and BCL-2 inhibitors may prove effective in the treatment of acute myeloid leukemia. Cancer Res; 78(11); 3075–86. ©2018 AACR.
Safety and Antitumor Activity of Pembrolizumab in Patients with Estrogen Receptor–Positive/Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer
Authors: Rugo Hope S. , Delord Jean-Pierre , Im Seock-Ah , Ott Patrick A. , Piha-Paul Sarina A. , Bedard Philippe L. , Sachdev Jasgit , Tourneau Christophe Le , van Brummelen Emilie M.J. , Varga Andrea , Salgado Roberto , Loi Sherene , Saraf Sanatan , Pietrangelo Dina , Karantza Vassiliki , Tan Antoinette R. 
Published: March 2018

Abstract
Purpose: We investigated the safety and antitumor activity of the anti–programmed death 1 monoclonal antibody pembrolizumab in patients with estrogen receptor–positive (ER+)/human epidermal growth factor receptor 2–negative (HER2−) advanced breast cancer with programmed death ligand 1–positive (PD-L1–positive) tumors in the phase Ib open-label, multicohort KEYNOTE-028 (NCT02054806) study.
Patients and Methods: Patients with ER+/HER2− advanced breast cancer with PD-L1–positive tumors (combined positive score ≥1) received pembrolizumab (10 mg/kg every 2 weeks) up to 2 years or until confirmed progression/intolerable toxicity. Primary endpoints were safety and overall response rate (ORR), based on Response Evaluation Criteria in Solid Tumors, version 1 (RECIST v1.1) as assessed by investigator review.
Results: Between April 2014 and January 2015, 25 patients were enrolled. Median number of prior therapies for breast cancer, including endocrine agents, was 9 (range, 3–15). Median follow-up was 9.7 months (range, 0.7–31.8 months). Three patients experienced partial response (PR) and none experienced complete response (CR), resulting in an ORR of 12.0% (95% CI, 2.5%–31.2%); 16% of patients had stable disease (SD) and clinical benefit rate (CR + PR + [SD for ≥24 weeks]) was 20% (95% CI, 7–41). Median duration of response was 12.0 months (range, 7.4–15.9 months). The incidence of treatment-related adverse events was 64%; nausea (20%) and fatigue (12%) were most common and were predominantly grade 1/2. No treatment-related discontinuations or deaths occurred.
Conclusions: Pembrolizumab was well tolerated with modest but durable overall response in certain patients with previously treated, advanced, PD-L1–positive, ER+/HER2− breast cancer. Clin Cancer Res; 24(12); 2804–11. ©2018 AACR.
Mean Platelet Volume as a Predictor for Restenosis After Carotid Angioplasty and Stenting
Authors: Dai Zhengze , Gao Jie , Li Shun , Li Rongrong , Chen Zhaoyao , Liang Meng , Liu Xinfeng , Xu Gelin 
Published: March 2018

Background and Purpose—
Platelet aggregation plays a vital role in the development of in-stent restenosis (ISR) after carotid angioplasty and stenting (CAS). Mean platelet volume (MPV) has been suggested as an index of platelet reactivity. This study aimed to investigate the association between MPV and ISR in CAS patients.

Methods—
A total of 261 patients with CAS were enrolled. MPV was measured before CAS procedure. Digital subtraction angiography, computed tomographic angiography, or duplex ultrasonography was performed at 6 months and annually after the procedure. ISR was defined as ≥50% stenosis in the treated lesion. Cox regression was used to identify predictors of ISR after CAS.

Results—
Of the 261 patients with CAS, 46 (17.6%) were determined with ISR during a mean follow-up of 12.1±16.1 months (range, 2.1–120.7). On multivariate analysis, baseline MPV >10.1 fL (hazard ratio, 3.20; 95% confidence interval, 1.28–8.03), lesion length (hazard ratio, 1.05; 95% confidence interval, 1.02–1.08), residual stenosis (hazard ratio, 1.07; 95% confidence interval, 1.05–1.10), and baseline glucose (hazard ratio, 1.01; 95% confidence interval, 1.00–1.02) were associated with ISR.

Conclusions—
Elevated MPV may be associated with ISR after CAS. Patients with high preprocedural MPV may benefit from an intensified antiplatelet therapy after CAS.
Spring Arctic Atmospheric Preconditioning: Do Not Rule Out Shortwave Radiation Just Yet
Authors: Sedlar Joseph 
Published: March 2018

Abstract
Springtime atmospheric preconditioning of Arctic sea ice for enhanced or buffered sea ice melt during the subsequent melt year has received considerable research focus. Studies have identified enhanced poleward atmospheric transport of moisture and heat during spring, leading to increased emission of longwave radiation to the surface. Simultaneously, these studies ruled out the role of shortwave radiation as an effective preconditioning mechanism because of relatively weak incident solar radiation, high surface albedo from sea ice and snow, and increased clouds during spring. These conclusions are derived primarily from atmospheric reanalysis, which may not always accurately represent the Arctic climate system. Here, top-of-atmosphere shortwave radiation observations from a state-of-the-art satellite sensor are compared with ERA-Interim reanalysis to examine similarities and differences in the springtime absorbed shortwave radiation (ASR) over the Arctic Ocean. Distinct biases in regional location and absolute magnitude of ASR anomalies are found between satellite-based measurements and reanalysis. Observations indicate separability between ASR anomalies in spring corresponding to anomalously low and high ice extents in September; the reanalysis fails to capture the full extent of this separability. The causes for the difference in ASR anomalies between observations and reanalysis are considered in terms of the variability in surface albedo and cloud presence. Additionally, biases in reanalysis cloud water during spring are presented and are considered for their impact on overestimating spring downwelling longwave anomalies. Taken together, shortwave radiation should not be overlooked as a contributing mechanism to springtime Arctic atmospheric preconditioning.
Homogenization and Trend Analysis of the 1958–2016 In Situ Surface Solar Radiation Records in China
Authors: Yang Su , Wang Xiaolan L. , Wild Martin 
Published: March 2018

Abstract
This paper presents a method to homogenize China’s surface solar radiation (SSR) data and uses the resulting homogenized SSR data to assess the SSR trend over the period 1958–2016. Neighboring surface sunshine duration (SSD) data are used as reference data to assess the SSR data homogeneity. A principal component analysis is applied to build a reference series, which is proven to be less sensitive to occasional data issues than using the arithmetic mean of data from adjacent stations. A relative or absolute test is applied to detect changepoints, depending on whether or not a suitable reference series is available. A quantile-matching method is used to adjust the data to diminish the inhomogeneities. As a result, 60 out of the 119 SSR stations were found to have inhomogeneity issues. These were mainly caused by changes in instrument and observation schedule. The nonclimatic changes exaggerated the SSR change rates in 1991–93 and resulted in a sudden rise in the national average SSR series, causing an unrealistically drastic trend reversal in the 1990s. This was diminished by the data homogenization. The homogenized data show that the national average SSR has been declining significantly over the period 1958–90; this dimming trend mostly diminished over the period 1991–2005 and was replaced by a brightening trend in the recent decade. From the homogenized SSR data, the 1958–90 and 1958–2005 dimming rate is estimated to be −6.13 ± 0.47 and −5.08 ± 0.27 W m−2 decade−1, respectively, and the 2005–16 brightening rate is 6.13 ± 1.77 W m−2 decade−1.
Observed Energy Exchange between Low-Frequency Flows and Internal Waves in the Gulf of Mexico
Authors: Jing Zhao , Chang Ping , DiMarco S. F. , Wu Lixin 
Published: March 2018

AbstractA long-term mooring array deployed in the northern Gulf of Mexico is used to analyze energy exchange between internal waves and low-frequency flows. In the subthermocline (245–450 m), there is a noticeable net energy transfer from low-frequency flows, defined as having a period longer than six inertial periods, to internal waves. The magnitude of energy transfer rate depends on the Okubo–Weiss parameter of low-frequency flows. A permanent energy exchange occurs only when the Okubo–Weiss parameter is positive. The near-inertial internal waves (NIWs) make major contribution to the energy exchange owing to their energetic wave stress and relatively stronger interaction with low-frequency flows compared to the high-frequency internal waves. There is some evidence that the permanent energy exchange between low-frequency flows and NIWs is attributed to the partial realization of the wave capture mechanism. In the periods favoring the occurrence of the wave capture mechanism, the horizontal propagation direction of NIWs becomes anisotropic and exhibits evident tendency toward that predicted from the wave capture mechanism, leading to pronounced energy transfer from low-frequency flows to NIWs.
Effect of Intranasal Insulin on Olfactory Recovery in Patients with Hyposmia: A Randomized Clinical Trial
Authors: Rezaeian Ahmad 
Published: March 2018

ObjectiveHyposmia is a sensorial disorder in which patients have a reduced sense of smell. However, there are no effective regimens for the management of this disorder. Therefore, the aim of this study is to evaluate the therapeutic effect of intranasal insulin on olfactory recovery in patients with hyposmia.Study DesignThis is a double‐blinded, randomized controlled trial.SettingIntervention.Subjects and MethodsThis study was administered on 38 patients with hyposmia according to the inclusion and exclusion criteria. Patients were randomly divided into 2 parallel groups. The intervention and placebo groups underwent endoscopic placement of intranasal insulin gel foam (40 IU) and saline‐soaked gel foam into the olfactory cleft, respectively. The procedure was performed twice a week for 4 weeks with butanol threshold testing initially and 4 weeks after treatment.ResultsThe Connecticut Chemosensory Clinical Research Center score in the intervention group was significantly higher compared to that of the placebo group after 4 weeks (P =. 01). Moreover, no adverse effects were reported in both groups.ConclusionOur findings indicated that intranasal insulin (40 IU) administration may trigger the improvement in the olfactory sense and also appears to be free of significant adverse events in this small cohort. However, due to limited research regarding this topic, further studies using a larger population are required.
Prognostic Role of Neutrophil‐to‐Lymphocyte Ratio in Patients with Human Papillomavirus–Positive Oropharyngeal Cancer
Authors: So Yoon Kyoung , Lee GilJoon , Oh Dongryul , Byeon Sunju , Park Woori , Chung Man Ki 
Published: March 2018

ObjectiveTo investigate the prognostic impact of the neutrophil‐to‐lymphocyte ratio (NLR) for human papillomavirus–positive oropharyngeal cancer (HPV+ OPC).Study DesignRetrospective institutional database analysis.SettingTertiary referral medical center.Material and MethodsIn total, 104 patients with HPV+ OPC were enrolled. From the blood laboratory data checked within 4 weeks before initiation of primary treatment, NLR was calculated. The association between clinicopathological characteristics and NLR was analyzed, and the prognostic role was evaluated based on overall survival (OS) and disease‐free survival (DFS).ResultsAccording to the cutoff value (2.42) for NLR, the patients were classified into the low NLR group (n = 61) or the high NLR group (n = 43). High NLR was associated with a higher rate of advanced T classification (P =. 007) and diabetes mellitus (P =. 01). The proportion of surgery‐based treatment was lower in the high NLR group (20.9% vs 42.6%, P =. 02). The high NLR group showed a lower 5‐year OS rate (85.3% vs 96.3%, P =. 09) and a lower 5‐year DFS rate (68.1% vs 94.7%, P =. 01) than those in the low NLR group. Multivariate analysis showed that advanced N classification was a significant predictor for worse 5‐year OS (hazard ratio [HR], 17.40; 95% confidence interval [CI], 2.36‐128.29) and that both advanced N classification (HR, 7.78; 95% CI, 2.33‐25.93) and high NLR (HR, 4.16; 95% CI, 1.24‐13.95) were important prognosticators for worse 5‐year DFS.ConclusionElevated pretreatment NLR was associated with poor DFS in patients with HPV+ OPC.
Opioids and the Otolaryngologist: An Ambulatory Assessment
Authors: Mohan Suresh , Bhattacharyya Neil 
Published: March 2018

ObjectivesTo recognize current opioid prescription patterns in otolaryngology and determine changes in rates of outpatient opioid prescribing over time.Study DesignCross‐sectional analysis of national survey database.SettingAmbulatory care settings in the United States.Subjects and MethodsThe National Ambulatory Medical Care Survey from 2006 to 2013 was analyzed for outpatient otolaryngology visits. The rate of opioid medication prescribing was determined with patient and visit characteristics associated with an opioid prescription, including corresponding diagnoses. Calendar trends for the rate of opioid prescribing were determined and compared biennially.ResultsAmong 19.2 ± 1.7 million otolaryngology visits annually (raw N = 11,905), there were 728,000 ± 96,000 visits with an opioid prescription (3.8% ± 0.4%). Adults were more likely than children to receive a narcotic (4.3% vs 1.9%, P <. 001); there was no significant difference according to sex (3.9% female vs 3.7% male, P =. 567). With respect to calendar trend, the opioid prescription rate increased significantly from 2.3% in 2006‐2007 to 4.6% in 2008‐2011 and then decreased to 3.5% in 2012‐2013 (P <. 031). The most common visit diagnosis categories associated with opioid prescribing were as follows: postoperative care (19.7% of prescriptions), adenotonsillitis (13.9%), chronic otitis media (8.7%), otitis externa (6.2%), and nasal obstruction (5.6%).ConclusionDespite the opioid epidemic in the United States, only a small portion of otolaryngology visits were associated with opioid prescription. However, given the significant increase in prescribing from 2008 to 2011, continued surveillance of prescribing patterns is warranted.
Valve Replacement for Chronic Mitral Insufficiency; Long-term Follow up Using Technetium Pertechnetate Scintigraphy
Authors: Reichart B. , Schad N. , Bougioukas G. , Kemkes B.M. , Kreuzer E. 
Published: March 2018

Technetium Pertechnetate Scintigraphy was performed in 12 patients (9 men and 3 women, average age 48 ± 13 years) on an average 19.8 ± 11 months after valve replacement for chronic mitral insufficiency. Preoperative conventional ventriculography had revealed increased enddiastolic and endsystolic volumes (230.9 ± 66 resp. 73.5 ± 26 ml). 59.4 ± 9% of the stroke volume (157.5 ± 47 ml) regurgitated into the left atrium. Ejection-fraction (67.7 ± 6%) was normal in all cases. Postoperative first pass technique was employed using a fast multicrystal camera (Baird Atomic, system 77). Volumes were assessed measuring normalized total count rate (count integral of the left ventricle divided by the maximum count density). 19.8 ± 11 months after valve replacement enddiastolic and endsystolic volumes revealed normal at rest (121.8 ± 38 resp. 52.8 ± 35 ml) and after maximum exercise (122.0 ± 29 resp. 37.6 ± 22 ml). Ejection fraction responded physiologically to exercise by rising from 57.7 ± 12 to 69.7 ± 10%.
Tc-99m-DTPA - a new Test Substance for Detoxification Devices
Authors: Ahrenholz P. , Falkenhagen D. , Roy T. , Esther G. , Klinkmann H. 
Published: March 2018

Tc99m labeled diethylenetriaminepentaacetic acid (Tc-99m-DTPA) is an appropriate in vivo test solute for all extracorporeal detoxification procedures. The molecular weight of the Tc-99m-DTPA complex is within the biologically relevant middle molecular range of 400 to 700 daltons. Tc-99m-DTPA is distributed in the extracellular space in the same way as inulin. Regarding its localization in the gel filtration spectra and plasma clearance, Tc-99m-DTPA corresponds to middle molecule peak 2. The evaluation of elimination rate and plasma clearance CP of Tc-99m-DTPA is possible by measuring the pulse rates before and after the detoxification device. Taking into account the corrections for Ht and UFR, the Tc-99m-DTPA plasma clearances were calculated for different dialyzers, high flux dialyzers, hemofilters and a hemoperfusion device. The continuous measurement of pulse rates and the use of a UFR-controller (A2008) allow an exact tracking of CP vs. time, the estimation of CP(QB), CP(UFR) and of the sieving coefficient. Examples are given for these cases. It was shown that an increase in plasma clearance to more than about 100 ml/min does not greatly increase the Tc-99m-DTPA elimination rate.