bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving MRCP PACES pass rates through the introduction of a regional multifaceted support framework
Authors: Jerrom Richard , Roper Tayeba , Murthy Narasimha 
Published: August 2017

IntroductionPractical Assessment of Clinical Examination Skills (PACES) constitutes the final part of the mandatory Royal College of Physicians exam series for progression to higher specialty training. Pass rates were lower for core medical trainees (CMTs) in Coventry and Warwickshire in comparison to other regions within the West Midlands and nationally.ObjectivesOur aim was to improve pass rates in the region through the introduction of a stimulating and supportive teaching framework, designed to enhance the quality and frequency of PACES teaching.MethodsTo identify key areas for change a baseline questionnaire, including Likert Scale and free text questions related to PACES teaching, was distributed to all CMTs in the region. Many trainees highlighted concern over lack of PACES-orientated teaching and support, with particular emphasis on: lack of bedside-teaching with feedback; infrequent opportunities for practising communication skills; and difficulty identifying suitable patients in an efficient manner. To address these concerns the following interventions were implemented over two Plan, Do, Study, Act (PDSA) cycles which were analysed at 6 months and 12months: a digital forum to highlight relevant inpatients for examination practice; a peer-to-peer mentoring scheme; a consultant-led bedside-teaching rota; and classroom-based communication skills sessions.ResultsPass rates at Annual Review of Competence Progression improved from baseline to the end of the first year of implementation, 56.3% to 77.3%, respectively. Furthermore, following analysis of questionnaires at each PDSA cycle, we demonstrated a progressive improvement in trainee satisfaction in exposure, quality and relevance of teaching.ConclusionOur innovative, cost-effective teaching framework for PACES preparation has improved exam outcomes and facilitated swift junior doctor career progression, while raising the profile of the trust. Furthermore, this innovation provides a template for potential adoption in other National Health Service institutions.
Corticospinal excitability of the biceps brachii is shoulder position dependent
Authors: Collins Brandon Wayne , Cadigan Edward W. J. , Stefanelli Lucas , Button Duane C. 
Published: August 2017

The purpose of this study was to examine the effect of shoulder position on corticospinal excitability (CSE) of the biceps brachii during rest and a 10% maximal voluntary contraction (MVC). Participants ( n = 9) completed two experimental sessions with four conditions: 1) rest, 0° shoulder flexion; 2) 10% MVC, 0° shoulder flexion; 3) rest, 90° shoulder flexion; and 4) 10% MVC, 90° shoulder flexion. Transcranial magnetic, transmastoid electrical, and Erb’s point stimulation were used to induce motor-evoked potentials (MEPs), cervicomedullary MEPs (CMEPs), and maximal muscle compound potentials (Mmax), respectively, in the biceps brachii in each condition. At rest, MEP, CMEP, and Mmax amplitudes increased ( P < 0.01) by 509.7 ± 118.3%, 113.3 ± 28.3%, and 155.1 ± 47.9%, respectively, at 90° compared with 0°. At 10% MVC, MEP amplitudes did not differ ( P = 0.08), but CMEP and Mmax amplitudes increased ( P < 0.05) by 32.3 ± 10.5% and 127.9 ± 26.1%, respectively, at 90° compared with 0°. MEP/Mmax increased ( P < 0.01) by 224.0 ± 99.1% at rest and decreased ( P < 0.05) by 51.3 ± 6.7% at 10% MVC at 90° compared with 0°. CMEP/Mmax was not different ( P = 0.22) at rest but decreased ( P < 0.01) at 10% MVC by 33.6 ± 6.1% at 90° compared with 0°. EMG increased ( P < 0.001) by 8.3 ± 2.0% at rest and decreased ( P < 0.001) by 21.4 ± 4.4% at 10% MVC at 90° compared with 0°. In conclusion, CSE of the biceps brachii was dependent on shoulder position, and the pattern of change was altered within the state in which it was measured. The position-dependent changes in Mmax amplitude, EMG, and CSE itself all contribute to the overall change in CSE of the biceps brachii. NEW & NOTEWORTHY We demonstrate that when the shoulder is placed into two common positions for determining elbow flexor force and activation, corticospinal excitability (CSE) of the biceps brachii is both shoulder position and state dependent. At rest, when the shoulder is flexed from 0° to 90°, supraspinal factors predominantly alter CSE, whereas during a slight contraction, spinal factors predominantly alter CSE. Finally, the normalization techniques frequently used by researchers to investigate CSE may under- and overestimate CSE when shoulder position is changed.
Method to remove photoreceptors from whole mount retina in vitro
Authors: Walston Steven T. , Chang Yao-Chuan , Weiland James D. , Chow Robert H. 
Published: August 2017

Patch clamp recordings of neurons in the inner nuclear layer of the retina are difficult to conduct in a whole mount retina preparation because surrounding neurons block the path of the patch pipette. Vertical slice preparations or dissociated retinal cells provide access to bipolar cells at the cost of severing the lateral connection between neurons. We have developed a technique to remove photoreceptors from the rodent retina that exposes inner nuclear layer neurons, allowing access for patch clamp recording. Repeated application to and removal of filter paper from the photoreceptor side of an isolated retina effectively and efficiently removes photoreceptor cells and, in degenerate retina, hypertrophied Müller cell end feet. Live-dead assays applied to neurons remaining after photoreceptor removal demonstrated mostly viable cells. Patch clamp recordings from bipolar cells reveal responses similar to those recorded in traditional slice and dissociated cell preparations. An advantage of the photoreceptor peel technique is that it exposes inner retinal neurons in a whole mount retina preparation for investigation of signal processing. A disadvantage is that photoreceptor removal alters input to remaining retinal neurons. The technique may be useful for investigations of extracellular electrical stimulation, photoreceptor DNA analysis, and nonpharmacological removal of light input. NEW & NOTEWORTHY This study reports a method for removing photoreceptors from rodent whole mount retina while preserving the architecture of the inner retina. The method enables easier access to the inner retina for studies of neural processing, such as by patch clamp recording.
Low-Dose Cyclophosphamide Induces Antitumor T-Cell Responses, which Associate with Survival in Metastatic Colorectal Cancer
Authors: Scurr Martin , Pembroke Tom , Bloom Anja , Roberts David , Thomson Amanda , Smart Kathryn , Bridgeman Hayley , Adams Richard , Brewster Alison , Jones Robert , Gwynne Sarah , Blount Daniel , Harrop Richard , Hills Robert , Gallimore Awen , Godkin Andrew 
Published: August 2017

Abstract
Purpose: Anticancer T-cell responses can control tumors, but immunosuppressive mechanisms in vivo prevent their function. The role of regulatory T cells (Tregs) in metastatic colorectal cancer is unclear. We have previously shown depletion of Tregs enhances colorectal cancer–specific effector T-cell responses. Low-dose cyclophosphamide targets Tregs in animal models and some human studies; however, the effect of cyclophosphamide in metastatic colorectal cancer is unknown.
Experimental Design: Fifty-five patients with metastatic colorectal cancer were enrolled in a phase I/II trial and randomly assigned to receive 2-week-long courses of low-dose (50 mg twice a day) cyclophosphamide or not. The absolute number, phenotype, and antitumor function of peripheral blood–derived lymphocyte subsets were monitored throughout treatment, as well as during 18-month follow-up.
Results: Initially, cyclophosphamide reduced proliferation in all lymphocyte subsets; however, a rapid mobilization of effector T cells overcame this decrease, leading to increased absolute T-cell numbers. In contrast, a reduction in proportional and absolute Treg, B-cell, and NK-cell numbers occurred. The expansion and subsequent activation of effector T cells was focused on tumor-specific T cells, producing both granzyme B and IFNγ. Cyclophosphamide-treated patients demonstrating the most enhanced IFNγ+ tumor-specific T-cell responses exhibited a significant delay in tumor progression [HR = 0.29; 95% confidence interval (CI), 0.12–0.69; P = 0.0047), compared with nonresponders and no-treatment controls.
Conclusions: Cyclophosphamide-induced Treg depletion is mirrored by a striking boost in antitumor immunity. This study provides the first direct evidence of the benefit of naturally primed T cells in patients with metastatic colorectal cancer. Our results also support the concept that nonmutated self-antigens may act as useful targets for immunotherapies. Clin Cancer Res; 23(22); 6771–80. ©2017 AACR.
Genomic Analysis of Nasopharyngeal Carcinoma Reveals TME-Based Subtypes
Authors: Zhang Li , MacIsaac Kenzie D. , Zhou Ting , Huang Pei-Yu , Xin Chunlin , Dobson Jason R. , Yu Kun , Chiang Derek Y. , Fan Yue , Pelletier Marc , Wang Yan , Jaeger Savina , Krishnamurthy Radhakrishnan Viveksagar , JeBailey Lellean , Skewes-Cox Peter , Zhang Jing , Fang Wenfeng , Huang Yan , Zhao Hongyun , Zhao Yuanyuan , Li En , Peng Bin , Huang Alan , Dranoff Glenn , Hammerman Peter S. , Engelman Jeffrey , Bitter Hans , Zeng Yi-Xin , Yao Yao 
Published: August 2017

Abstract
Nasopharyngeal carcinoma (NPC) is an Epstein–Barr virus (EBV) associated cancer characterized by a poor prognosis and a high level of lymphocyte infiltrate. Genetic hallmarks of NPC are not completely known but include deletion of the p16 (CDKN2A) locus and mutations in NF-κB pathway components, with a relatively low total mutational load. To better understand the genetic landscape, an integrated genomic analysis was performed using a large clinical cohort of treatment-naïve NPC tumor specimens. This genomic analysis was generally concordant with previous studies; however, three subtypes of NPC were identified by differences in immune cell gene expression, prognosis, tumor cell morphology, and genetic characteristics. A gene expression signature of proliferation was poorly prognostic and associated with either higher mutation load or specific EBV gene expression patterns in a subtype-specific manner. Finally, higher levels of stromal tumor-infiltrating lymphocytes associated with good prognosis and lower expression of a WNT and TGFβ pathway activation signature.
Implications: This study represents the first integrated analysis of mutation, copy number, and gene expression data in NPC and suggests how tumor genetics and EBV infection influence the tumor microenvironment in this disease. These insights should be considered for guiding immunotherapy treatment strategies in this disease. Mol Cancer Res; 15(12); 1722–32. ©2017 AACR.
The MiTF/TFE Family of Transcription Factors: Master Regulators of Organelle Signaling, Metabolism, and Stress Adaptation
Authors: Slade Logan , Pulinilkunnil Thomas 
Published: August 2017

Abstract
The microphthalmia family (MITF, TFEB, TFE3, and TFEC) of transcription factors is emerging as global regulators of cancer cell survival and energy metabolism, both through the promotion of lysosomal genes as well as newly characterized targets, such as oxidative metabolism and the oxidative stress response. In addition, MiT/TFE factors can regulate lysosomal signaling, which includes the mTORC1 and Wnt/β-catenin pathways, which are both substantial contributors to oncogenic signaling. This review describes recent discoveries in MiT/TFE research and how they impact multiple cancer subtypes. Furthermore, the literature relating to TFE-fusion proteins in cancers and the potential mechanisms through which these genomic rearrangements promote tumorigenesis is reviewed. Likewise, the emerging function of the Folliculin (FLCN) tumor suppressor in negatively regulating the MiT/TFE family and how loss of this pathway promotes cancer is examined. Recent reports are also presented that relate to the role of MiT/TFE–driven lysosomal biogenesis in sustaining cancer cell metabolism and signaling in nutrient-limiting conditions. Finally, a discussion is provided on the future directions and unanswered questions in the field. In summary, the research surrounding the MiT/TFE family indicates that these transcription factors are promising therapeutic targets and biomarkers for cancers that thrive in stressful niches. Mol Cancer Res; 15(12); 1637–43. ©2017 AACR.
The Second-Generation PGI2 Analogue Treprostinil Fails to Chemoprevent Tumors in a Murine Lung Adenocarcinoma Model
Authors: Dwyer-Nield Lori , Hickey Gregory A. , Friedman Micah , Choo Kevin , McArthur Debbie G. , Tennis Meredith A. , New Melissa L. , Geraci Mark , Keith Robert L. 
Published: August 2017

Abstract
Prostacyclin (prostaglandin I2, PGI2) overproduction in FVB/N mice prevents the formation of carcinogen and tobacco smoke–induced adenomas, and administration of the oral prostacyclin analogue iloprost to wild-type mice also prevented carcinogen-induced mouse lung adenoma formation. Former smokers taking oral iloprost showed improved bronchial dysplasia histology compared with placebo. Next-generation oral prostacyclin analogues, like treprostinil, were developed for the treatment of pulmonary arterial hypertension (PAH). On the basis of our prior studies with iloprost, we performed preclinical studies examining the ability of treprostinil to chemoprevent urethane-induced murine lung adenocarcinoma. We determined the MTD in chow (prior studies had delivered treprostinil by gavage), and this dose produced serum levels in the experimental animals similar to those found in PAH patients treated with treprostinil. We then examined the chemopreventive efficacy of treprostinil exposure initiated both before (1 week) and after (6 weeks) urethane exposure to better model chemoprevention studies conducted in former smokers. Neither of these dosing strategies prevented murine lung cancer; however, we did detect changes in pulmonary inflammatory cell infiltrate and expression of CXCR4 (a chemokine receptor previously shown to increase in response to treprostinil exposure) in tumor-bearing, treprostinil-treated animals, indicating that the drug was bioavailable. One potential explanation stems from iloprost and treprostinil differentially activating cell surface prostaglandin receptors and intracellular peroxisome proliferator-activated receptors. When murine lung tumor cells were treated with treprostinil, their proliferation rate increased; in contrast, iloprost had no effect on proliferation. Future investigations comparing these two agents will provide insight into iloprost's chemopreventive mechanisms. Cancer Prev Res; 10(11); 671–9. ©2017 AACR.
Photodynamic-Immune Checkpoint Therapy Eradicates Local and Distant Tumors by CD8+ T Cells
Authors: Kleinovink Jan Willem , Fransen Marieke F. , Löwik Clemens W. , Ossendorp Ferry 
Published: August 2017

Abstract
Photodynamic therapy (PDT) is a clinically applied tumor ablation method that reduces tumor burden and may induce T-cell responses, providing a therapeutic option for mutated tumors. In this study, we applied PDT in two mouse tumor models and assessed its effect on outgrowth of PDT-treated and distant untreated tumors. PDT of established tumors resulted in complete tumor eradication in most mice, which were then protected against tumor rechallenge. Correspondingly, the therapeutic effect was abrogated upon systemic depletion of CD8+ T cells, indicating PDT-induced tumor antigen cross-presentation and T-cell activation. In a double-tumor model, PDT of primary tumors induced enhanced infiltration of untreated distant tumors by CD8+ T cells, which significantly delayed their outgrowth. Combination therapy of PDT and CTLA-4–blocking antibodies significantly improved therapeutic efficacy and survival of double-tumor–bearing mice. These results show that local tumor ablation by PDT induces CD8+ T-cell responses crucial for systemic tumor eradication, which can be further enhanced by combination with immune checkpoint blockade. This combination of two clinically applied therapies may be a treatment strategy for advanced cancer without previous knowledge of tumor-specific antigens. Cancer Immunol Res; 5(10); 832–8. ©2017 AACR.
An Analytical Approach for DG Placement in Reconfigured Distribution Networks
Authors: Nawaz Sarfaraz , Bansal Ajay , Sharma M. P. 
Published: August 2017

<p>A novel approach is proposed in this paper for optimal placement of DG units in reconfigured distribution system with the aim of reduction of real power losses while satisfying operating constraints. The proposed analytical method for optimal DG placement is developed based on a new mathematical formulation. Type-I and type-II DG units are used here. The results of the proposed technique are validated on IEEE 69 bus distribution system. The level of DG penetration is also considered in a range of 0–50% of total system load. A novel index is also proposed which incorporates level of DG penetration and percentage reduction in real power losses. The results are promising when compared with recently proposed algorithms.</p>
Surgical and Catheter-Based Reinterventions Are Common in Long-Term Survivors of the Fontan Operation
Authors: Downing Tacy E. , Allen Kiona Y. , Goldberg David J. , Rogers Lindsay S. , Ravishankar Chitra , Rychik Jack , Fuller Stephanie , Montenegro Lisa M. , Steven James M. , Gillespie Matthew J. , Rome Jonathan J. , Spray Thomas L. , Nicolson Susan C. , Gaynor J. William , Glatz Andrew C. 
Published: August 2017

Background—
There are limited follow-up studies examining surgical and catheter-based reinterventions in long-term survivors of the Fontan operation.

Methods and Results—

All 773 patients who underwent Fontan at our institution between 1992 and 2009 were retrospectively reviewed. Current information regarding post-Fontan intervention was available for 70%. By 20 years after Fontan, 65% of patients had experienced either surgical or transcatheter intervention. The median time to first reintervention was 9.8 years. Freedom from reoperation was 69% at 15 years and 63% at 20 years. The most common operations were pacemaker placement and Fontan revision. Risk factors for pacemaker placement included systemic left ventricle (hazard ratio [HR], 2.2;
P
=0.006) and lateral tunnel Fontan (HR, 4.3;
P
=0.001). Freedom from interventional catheterization was 53% at 15 years and 50% at 20 years. The most common procedures performed were fenestration closure and pulmonary artery intervention. Catheter intervention for anatomic indications was associated with Fontan after 2002 (HR, 2.1;
P
=0.007), Norwood operation (HR, 2.3;
P
=0.001), and longer cardiopulmonary bypass time (HR, 1.1 per 10 minutes;
P
=0.001). Catheter intervention for physiological indications was associated with prolonged post-Fontan pleural drainage (HR, 4.0;
P
<0.001) and hypoplastic left heart syndrome (HR, 2.0;
P
=0.01).

Conclusions—
In this study of Fontan survivors, two thirds of patients required surgical or catheter-based reintervention by 20 years. Families should be counseled that the Fontan is typically not the final stage of single-ventricle palliation.
Description of Abnormal Breathing Is Associated With Improved Outcomes and Delayed Telephone Cardiopulmonary Resuscitation Instructions
Authors: Fukushima Hidetada , Panczyk Micah , Hu Chengcheng , Dameff Christian , Chikani Vatsal , Vadeboncoeur Tyler , Spaite Daniel W. , Bobrow Bentley J. 
Published: August 2017

Background

Emergency 9‐1‐1 callers use a wide range of terms to describe abnormal breathing in persons with out‐of‐hospital cardiac arrest (
OHCA
). These breathing descriptors can obstruct the telephone cardiopulmonary resuscitation (
CPR
) process.

Methods and Results

We conducted an observational study of emergency call audio recordings linked to confirmed
OHCA
s in a statewide Utstein‐style database. Breathing descriptors fell into 1 of 8 groups (eg, gasping, snoring). We divided the study population into groups with and without descriptors for abnormal breathing to investigate the impact of these descriptors on patient outcomes and telephone
CPR
process. Callers used descriptors in 459 of 2411 cases (19.0%) between October 1, 2010, and December 31, 2014. Survival outcome was better when the caller used a breathing descriptor (19.6% versus 8.8%,
P
<0.0001), with an odds ratio of 1.63 (95% confidence interval, 1.17–2.25). After exclusions, 379 of 459 cases were eligible for process analysis. When callers described abnormal breathing, the rates of telecommunicator
OHCA
recognition,
CPR
instruction, and telephone
CPR
were lower than when callers did not use a breathing descriptor (79.7% versus 93.0%,
P
<0.0001; 65.4% versus 72.5%,
P
=0.0078; and 60.2% versus 66.9%,
P
=0.0123, respectively). The time interval between call receipt and
OHCA
recognition was longer when the caller used a breathing descriptor (118.5 versus 73.5 seconds,
P
<0.0001).

Conclusions

Descriptors of abnormal breathing are associated with improved outcomes but also with delays in the identification of
OHCA
. Familiarizing telecommunicators with these descriptors may improve the telephone
CPR
process including
OHCA
recognition for patients with increased probability of survival.
A new species of squat lobster of the genus Munida (Galatheoidea, Munididae) from the Red Sea
Authors: Macpherson E. , Beuck L. , Roder C. , Voolstra C. R. 
Published: August 2017

During a deep-water expedition to the Red Sea in 2013, an unusual specimen of squat lobster belonging to the genus Munida was collected off Thuwal, Saudi Arabia, at a depth of 320 m. This specimen is unique in having the pterygostomial flap visible from the dorsal side, the feature linking it to two eastern Pacific species, M. bapensis Hendrickx, 2000 and M. macrobrachia Hendrickx, 2003. The new species (M. tuerkayi) is readily distinguished from the eastern Pacific species by having the gastric region with numerous instead of less numerous spines, by having sternite 7 with three distinct carinae on each side, and by having the antennular basal article with two distal spines subequal instead of different in size. Munida tuerkayi was found associated with live colonies of the scleractinian coral Eguchipsammia fistula (Alcock, 1902).
Polymorphism in the chelae of mature males of the land crabs Johngarthia lagostoma and Epigrapsus spp.
Authors: Hartnoll Richard G. , Weber Nicola , Weber Sam B. , Liu Hung-Chang 
Published: August 2017

The growth of the chelae of mature males was examined in three gecarcinid land crabs — Johngarthia lagostoma on Ascension Island, Epigrapsus notatus on Taiwan, and E. politus on Moorea. Chelar dimorphism was found in each species, with a mixture of homochelous and heterochelous males. In J. lagostoma there was progressive polymorphism, with the heterochelous condition appearing only in a proportion of the larger mature males. The situation in Epigrapsus was less clear. The proportion of heterochelous males increased in the larger mature size classes, but progressive polymorphism is yet to be confirmed.