bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cadaveric surgery in core gynaecology training: a feasibility study
Authors: Lim Chou Phay , Roberts Mark , Chalhoub Tony , Waugh Jason , Delgaty Laura 
Published: January 2018

Abstract
Background
Fresh frozen cadaver training has been proposed as a better model than virtual reality simulators in laparoscopy training. We aimed to explore the relationship between cadaveric surgical training and increased surgical confidence.
To determine feasibility, we devised two 1-day cadaveric surgical training days targeted at trainees in obstetrics and gynaecology. Seven defined surgical skills were covered during the course of the day. The relationship between surgical training and surgical confidence was explored using both quantitative (confidence scores) and qualitative tools (questionnaires).

Results
Participants rated a consistent improvement in their level of confidence after the training. They universally found the experience positive and three overarching themes emerged from the qualitative analysis including self-concept, social persuasion and stability of task.

Conclusions
It is pragmatically feasible to provide procedure-specific cadaveric surgical training alongside supervised clinical training. This small, non-generalisable study suggests that cadaveric training may contribute to an increase in surgical self-confidence and efficacy. This will form the basis of a larger study and needs to be explored in more depth with a larger population.
New-Onset Cardiovascular Morbidity in Older Adults With Stage I to III Colorectal Cancer
Authors: Kenzik Kelly M. , Balentine Courtney , Richman Joshua , Kilgore Meredith , Bhatia Smita , Williams Grant R. 
Published: January 2018

Purpose We sought to determine the long-term risk of cardiovascular disease (CVD)—stroke and myocardial infarction—and congestive heart failure (CHF) in older patients with colorectal cancer, as well as to understand the roles that preexisting comorbidities and cancer therapy play in increasing this risk. Patients and Methods We evaluated individuals from the SEER-Medicare database with incident stage I to III colorectal cancer at age older than 65 years between January 1, 2000, and December 31, 2011 (n = 72,408) and compared these patients with a matched cohort of Medicare patients without cancer (n = 72,408). Results Median age at diagnosis of colorectal cancer was 78 years (range, 66 years to 106 years), and median follow-up was 8 years since diagnosis. The 10-year cumulative incidence of new-onset CVD and CHF were 57.4% and 54.5% compared with 22% and 18% for control, respectively ( P < .001). The interaction between hypertension and chemotherapy was significant ( P < .001) for CVD, and that between diabetes and chemotherapy was significant ( P < .001) for CHF. Within the first 2 years since diagnosis, exposure to capecitabine alone increased CHF hazard (hazard ratio [HR], 3.6; 95% CI, 12.76 to 4.38) compared with exposure to fluorouracil alone. Conversely, patients who were treated with fluorouracil alone had a higher CVD hazard at < 2 years and > 2 years since diagnosis compared with patients who received capecitabine alone (< 2 years HR, 0.63; 95% CI, 0.53 to 0.75; > 2 years HR, 0.72; 95% CI, 0.62 to 0.84). Conclusion Older patients with colorectal cancer are at increased risk of developing CVD and CHF. Diabetes and hypertension interact with chemotherapy to increase the risk of cardiovascular morbidity. Future studies should assess the potential for personalized therapeutic options for those with preexisting morbidities and for structured monitoring for patients with a history of exposure to chemotherapy regimens, as well as explore the management of preexisting comorbidities to address long-term cardiovascular morbidity.
Molecular Determinants of Response to Anti–Programmed Cell Death (PD)-1 and Anti–Programmed Death-Ligand 1 (PD-L1) Blockade in Patients With Non–Small-Cell Lung Cancer Profiled With Targeted Next-Generation Sequencing
Authors: Rizvi Hira , Sanchez-Vega Francisco , La Konnor , Chatila Walid , Jonsson Philip , Halpenny Darragh , Plodkowski Andrew , Long Niamh , Sauter Jennifer L. , Rekhtman Natasha , Hollmann Travis , Schalper Kurt A. , Gainor Justin F. , Shen Ronglai , Ni Ai , Arbour Kathryn C. , Merghoub Taha , Wolchok Jedd , Snyder Alexandra , Chaft Jamie E. , Kris Mark G. , Rudin Charles M. , Socci Nicholas D. , Berger Michael F. , Taylor Barry S. , Zehir Ahmet , Solit David B. , Arcila Maria E. , Ladanyi Marc , Riely Gregory J. , Schultz Nikolaus , Hellmann Matthew D. 
Published: January 2018

Purpose Treatment of advanced non–small-cell lung cancer with immune checkpoint inhibitors (ICIs) is characterized by durable responses and improved survival in a subset of patients. Clinically available tools to optimize use of ICIs and understand the molecular determinants of response are needed. Targeted next-generation sequencing (NGS) is increasingly routine, but its role in identifying predictors of response to ICIs is not known. Methods Detailed clinical annotation and response data were collected for patients with advanced non–small-cell lung cancer treated with anti–programmed death-1 or anti–programmed death-ligand 1 [anti-programmed cell death (PD)-1] therapy and profiled by targeted NGS (MSK-IMPACT; n = 240). Efficacy was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and durable clinical benefit (DCB) was defined as partial response/stable disease that lasted > 6 months. Tumor mutation burden (TMB), fraction of copy number–altered genome, and gene alterations were compared among patients with DCB and no durable benefit (NDB). Whole-exome sequencing (WES) was performed for 49 patients to compare quantification of TMB by targeted NGS versus WES. Results Estimates of TMB by targeted NGS correlated well with WES (ρ = 0.86; P < .001). TMB was greater in patients with DCB than with NDB ( P = .006). DCB was more common, and progression-free survival was longer in patients at increasing thresholds above versus below the 50th percentile of TMB (38.6% v 25.1%; P < .001; hazard ratio, 1.38; P = .024). The fraction of copy number–altered genome was highest in those with NDB. Variants in EGFR and STK11 associated with a lack of benefit. TMB and PD-L1 expression were independent variables, and a composite of TMB plus PD-L1 further enriched for benefit to ICIs. Conclusion Targeted NGS accurately estimates TMB and elevated TMB further improved likelihood of benefit to ICIs. TMB did not correlate with PD-L1 expression; both variables had similar predictive capacity. The incorporation of both TMB and PD-L1 expression into multivariable predictive models should result in greater predictive power.
Triazasumanene: An Isoelectronic Heteroanalogue of Sumanene
Authors: Tan Qitao , Kaewmati Patcharin , Higashibayashi Shuhei , Kawano Masaki , Yakiyama Yumi , Sakurai Hidehiro 
Published: January 2018

AbstractBuckybowls, which are represented by sumanene and corannulene, have attracted considerable attention for their unique bowl structures and interesting physicochemical properties. However, still few heteroatom-doped buckybowls have been reported to date. Here we show the successful synthesis of triazasumanene, an isoelectronic heteroanalogue of sumanene, which possesses a deeper bowl with stable bowl chirality and unique helical columnar packing in the crystal as an enantiopure form. In contrast, the crystal packing of the racemate shows a unidirectional columnar structure, which resembles that of the pristine sumanene. Doping of nitrogen atoms into the periphery of the sumanene framework also leads to perturbations of the electronic structure as shown by a significant decrease of the lowest unoccupied molecular orbital (LUMO) level and the optical band gap in comparison to all-carbon sumanene. The pyridine ring of triazasumanene shows unusual susceptibility towards acidic hydrolysis due to the highly strained curved structure.
Detection of Amine Vapors using Luminescent Xerogels from Supramolecular Metal-Containing Gelator
Authors: Sasaki Junpei , Suzuki Masahiro , Hanabusa Kenji 
Published: January 2018

Abstract
Supramolecular fluorescent gelators containing a tris(β-diketonato) complex are synthesized by using gelation-driving chelates, and their gelation abilities are studied with 15 solvents. Thin-layer films are prepared on quartz plates from the solutions and they are studied as chemosensors for amines. Fluorescence-quenching of the thin-layer films upon exposure to saturated primary and secondary amine vapors is monitored to evaluate the abilities of the chemosensors to detect amines. The morphologies of the thin-layer films are observed by transmission electron microscopy (TEM) and discussed in relation to their fluorescence-quenching. The fluorescence-quenching efficiencies upon exposure to saturated primary and secondary amines depend on the basicity and bulkiness of the amines rather than the vapor pressure. The fluorescence-quenching is caused by decomposition of a complex through nucleophilic addition of primary or secondary amines to its carbonyl group. The detection of tertiary amines is performed by monitoring the fluorescence emission from the thin-layer films, which are composed of a ligand and EuCl3. The emergence of fluorescence originates from the formation of fluorescent Eu3+-containing gelator, in which dehydrochloric acid by tertiary amines is a trigger for the complexation.
A comparison of physical activity and nutrition in young women with and without primary dysmenorrhea
Authors: Abadi Bavil Dina , Dolatian Mahrokh , Mahmoodi Zohreh , Akbarzadeh Baghban Alireza 
Published: January 2018

Background: Dysmenorrhea is the most common gynecological disorder in young women and is seen in almost 50% of women. The present study was conducted to investigate the relationship between physical activity and nutrition with primary dysmenorrhea in students at Mazandaran University of Medical Sciences (Sari, Iran) in 2015. Methods: This comparative descriptive study was conducted on 250 students with and without primary dysmenorrhea. Data were collected using personal-demographic, nutrition and physical activity questionnaires. The output was then analyzed in SPSS-18 using independent t-test, Chi-square test and logistic regression analysis. Results: The results showed significant differences between the two groups in terms of nutrition and physical activity, as the mean score of nutrition was 57.91 in the group with dysmenorrhea and 61.68 in the group without, while the mean intensity of physical activity was 5518.75 metric in the group with dysmenorrhea and 4666.42 metric in the group without. Physical activity was calculated by MET scale (minutes/week). This index measured the amount of consumed energy at the time of activity relative to that consumed at resting time. Conclusions: A healthier and more favorable nutrition style and more regular physical activity reduces the severity of dysmenorrhea in girls. Therefore, educational measures are required to raise awareness among young women about the effects of proper nutrition and physical activity on the prevention and reduction of dysmenorrhea complications.
Case Report: Acute amyopathic dermatomyositis presenting with isolated facial edema
Authors: Pappa Efthymia , Gkeka Marina , Protogerou Asimina , Marinos Leonidas , Loupa Chariclia , Christopoulos Constantinos 
Published: January 2018

A 45-year-old Asian man presented with acute-onset periorbital and facial edema associated with pyrexia. Muscle weakness was absent. Initial laboratory investigations showed an inflammatory reaction, while screening for infections was negative. Serum muscle enzyme levels were normal. He was hospitalized and treated empirically with antibiotics and corticosteroids, pending the result of facial skin and muscle biopsy. He showed a good clinical and laboratory response but an attempt to discontinue corticosteroids led to a prompt relapse of facial edema and pyrexia, associated with rising laboratory indices of inflammation. Biopsy findings were typical of dermatomyositis. Reintroduction of corticosteroid treatment resulted in complete clinical and laboratory remission. Facial edema as the sole clinical manifestation of dermatomyositis is extremely rare. There have been no previous reports of isolated facial edema in the setting of acute amyopathic dermatomyositis. A high level of suspicion is required to make the diagnosis in the absence of myopathy and the hallmark cutaneous manifestations of the disease (heliotrope rash, Gottron papules).
“Giving something back”: A systematic review and ethical enquiry of public opinions on the use of patient data for research in the United Kingdom and the Republic of Ireland
Authors: Stockdale Jessica , Cassell Jackie , Ford Elizabeth 
Published: January 2018

Background: Use of medical data for secondary purposes such as health research, audit, and service planning is well established in the UK. However, the governance environment, as well as public opinion and understanding about this work, have lagged behind. We aimed to systematically review the literature on UK and Irish public opinions of medical data use in research, critically analysing such opinions though an established biomedical ethics framework, to draw out potential strategies for future good practice guidance and inform ethical and privacy debates.Methods: We searched three databases using terms such as patient, public, opinion, and electronic health records. Empirical studies were eligible for inclusion if they surveyed healthcare users, patients or the wider public in UK and Ireland and examined attitudes, opinions or beliefs about the use of patient data for medical research. Results were synthesised into broad themes using a Framework Analysis.Results: Out of 13,492 papers and reports screened, 20 papers or reports were eligible. While there was a widespread willingness to share EHRs for research for the common good, this very rarely led to unqualified support. The public expressed two generalised concerns through a variety of hypothetical examples. The first of these concerns related to a party’s competence in keeping data secure, while the second was associated with the motivation a party might have to use the data.Conclusions: The public evaluates trustworthiness of research organisations by assessing their competence in data-handling and motivation for accessing the data. Public attitudes around data-sharing exemplified several principles which are also widely accepted in biomedical ethics. This provides a framework for understanding public attitudes, which should be considered in the development in any guidance for regulators and data custodians. We propose four salient questions which data guardians should address when evaluating proposals for the secondary use of data.
Once in the Door: Gender, Tryouts, and the Initial Salaries of Managers
Authors: Sterling Adina D. , Fernandez Roberto M. 
Published: January 2018

Although women pursue managerial credentials at nearly the same rate as men, gender disparities in wages exist because of the shortfall in wages women sustain relative to men at the onset of their careers. This article develops a tryout approach to test for the presence of demand-side contributions to initial wage inequality while also developing and testing theory on why it may be lessened through internships. Using detailed data on graduates from an elite management program from 2009–2010, our analyses reveal that internships are associated with the gap in men’s and women’s initial salaries. For men, there is no difference in salary offers from employers where an internship occurs versus one where an internship does not occur. However, women receive higher salaries from employers where an internship first takes place. This paper was accepted by Olav Sorenson, organizations.
Allele-Specific Droplet Digital PCR Combined with a Next-Generation Sequencing-Based Algorithm for Diagnostic Copy Number Analysis in Genes with High Homology: Proof of Concept Using Stereocilin
Authors: Amr Sami S , Murphy Elissa , Duffy Elizabeth , Niazi Rojeen , Balciuniene Jorune , Luo Minjie , Rehm Heidi L , Abou Tayoun Ahmad N 
Published: January 2018

Abstract

BACKGROUND
Copy number variants (CNVs) can substantially contribute to the pathogenic variant spectrum in several disease genes. The detection of this type of variant is complicated in genes with high homology to other genomic sequences, yet such genomics regions are more likely to lead to CNVs, making it critical to address detection in these settings.

METHODS
We developed a copy number analysis approach for high homology genes/regions that consisted of next-generation sequencing (NGS)-based dosage analysis accompanied by allele-specific droplet digital PCR (ddPCR) confirmatory testing. We applied this approach to copy number analysis in STRC, a gene with 98.9% homology to a nonfunctional pseudogene, pSTRC, and characterized its accuracy in detecting different copy number states by use of known samples.

RESULTS
Using a cohort of 517 patients with hearing loss, we prospectively demonstrated the clinical utility of the approach, which contributed 30 of the 122 total positives (6%) to the diagnostic yield, increasing the overall yield from 17.6% to 23.6%. Positive STRC genotypes included homozygous (n = 15) or compound heterozygous (n = 8) deletions, or heterozygous deletions in trans with pathogenic sequence variants (n = 7). Finally, this approach limited ddPCR testing to cases with NGS copy number findings, thus markedly reducing the number of costly and laborious, albeit specific, ddPCR tests.

CONCLUSIONS
NGS-based CNV detection followed by allele-specific ddPCR confirmatory testing is a reliable and affordable approach for copy number analysis in medically relevant genes with homology issues.
Specific Substrate for the Assay of Lysosomal Acid Lipase
Authors: Masi Sophia , Chennamaneni Naveen , Turecek Frantisek , Scott C Ronald , Gelb Michael H 
Published: January 2018

Abstract

BACKGROUND
Deficiency of lysosomal acid lipase (LAL) causes Wolman disease and cholesterol ester storage disease. With the recent introduction of enzyme replacement therapy to manage LAL deficiency comes the need for a reliable assay of LAL enzymatic activity that can be applied to dried blood spots (DBS).

METHODS
We prepared and tested a library of analogs of palmitoyl 4-methylumbelifferyl esters to find a highly active and specific substrate for LAL in DBS. The LAL assay was optimized leading to both LC-MS/MS and fluorometric assay of LAL. We tested the new assay on DBS from healthy and LAL-deficient patients.

RESULTS
The ester formed between palmitic acid and 4-propyl-8-methyl-7-hydroxycoumarin (P-PMHC) was found to be &gt;98% selective for LAL in DBS based on the sensitivity of its activity to the LAL-specific inactivator Lalistat-2 and the fact that the activity was close to zero using DBS from patients previously shown to be LAL-deficient. Use of P-PMHC and heavy isotope-labeled internal standard with optimized assay conditions led to an approximately 2-fold increase in the specific activity of LAL compared with the previously reported LAL assay. Patients deficient in LAL were readily distinguished from normal persons with the new LAL assay using UPLC-MS/MS or fluorometric assay platforms.

CONCLUSIONS
The new assay can measure LAL in DBS with a single measurement compared with the previous method involving 2 assays done in parallel.
Synthesis and evaluation of antitumor activity of new 4-substituted thieno[3,2-d]pyrimidine and thienotriazolopyrimidine derivatives
Authors: Hafez Hend N. , El-Gazzar Abdel-Rhman B. A. 
Published: January 2018

Abstract
3-Methyl-6-phenyl-2-thioxo-2,3-dihydrothieno[3,2-d]pyrimidin- 4(1H)-one (2), on treatment with phosphorous oxychoride, affored 4-chloro-3-methyl-6-phenyl -thieno[3,2-d]pyrimidine- 2(3H)-thione (3). A series of novel 6-phenyl-thieno[3,2-d]pyrimidine derivatives 4-9 bearing different functional groups were synthesized via treatment of compound 3 with different reagents. On the other hand, compound 2 was used to synthesize ethyl-[(3-methyl-6-phenyl-2-thioxo-2,3-dihydrothieno[ 3,2-d]pyrimidin-4-yl)-oxy]acetate (10), 2-hydrazinyl- -3-methyl-6-phenyl-thieno[3,2-d]pyrimidin-4(3H)-one (11), 3-methyl-2-(methyl-sulfanyl)-6-phenyl-thieno[3,2-d]pyrimidin- 4(3H)-one (12) and N-(phenyl)/4-chlorophenyl or methoxy- phenyl)-2-[(3-methyl-4-oxo-6-phenyl-3,4-dihydrothieno[ 3,2-d]pyrimidin-2-yl)-sulfanyl]-acetamide (13a-c). In addition, compound 12 was used to synthesize thieno[1,2,4] triazolopyrimidine derivatives 14 and 15 and 3-methyl-2-(methyl-sulfonyl)-6-phenyl-thieno[3,2-d]pyrimidin-4(3H)-one (16) through the reaction with the respective reagents. Moreover, the reaction of 16 with 4-phenylenediamine gave 2-[(4-aminophenyl)-amino]-3-methyl-6-phenyl-thieno[3,2-d] pyrimidin-4(3H)-one (17), which reacted with methanesulfonyl chloride to afford N-{4-[(3-methyl-4-oxo-6-phenyl-3H,4H- -thieno[3,2-d]pyrimidin-2-yl)-amino]phenyl}-methanesulfonamide (18). The majority of the newly synthesized compounds displayed potent anticancer activity, comparable to that of doxorubicin, on three human cancer cell lines, including the human breast adenocarcinoma cell line (MCF-7), cervical carcinoma cell line (HeLa) and colonic carcinoma cell line (HCT- 116). Compounds 18, 13b and 10 were nearly as active as doxorubicin whereas compounds 6, 7b and 15 exhibited marked growth inhibition, but still lower than doxorubicin.
The Effect of Cooling Agent on Stress and Deformation of Charge-loaded Cast Pallets
Authors: Bajwoluk A. , Gutowski P. 
Published: January 2018

Abstract
The results of research on the effect of the type of cooling agent used during heat treatment and thermal-chemical treatment on the formation of temperature gradient and stress-deformation distribution in cast pallets, which are part of furnace accessories used in this treatment, are disclosed. During operation, pallets are exposed to the effect of the same conditions as the charge they are carrying. Cyclic thermal loads are the main cause of excessive deformations or cracks, which after some time of the cast pallet operation result in its withdrawal due to damage. One of the major causes of this damage are stresses formed under the effect of temperature gradient in the unevenly cooled pallet construction. Studies focused on the analysis of heat flow in a charge-loaded pallet, cooled by various cooling agents characterized by different heat transfer coefficients and temperature. Based on the obtained temperature distribution, the stress distribution and the resulting deformation were examined. The results enabled drawing relevant conclusions about the effect of cooling conditions on stresses formed in the direction of the largest temperature gradient.
TG/DTG/DTA, FTIR and GC/MS Studies of Oil Sand for Artistic and Precision Foundry with the Emission of Gases Assessment
Authors: Bobrowski A. , Żymankowska-Kumon S. , Drożyński D. , Grabowska B. , Kaczmarska K. 
Published: January 2018

AbstractThe paper presents the results of thermoanalytical studies by TG/DTG/DTA, FTIR and GC/MS for the oil sand used in art and precision foundry. On the basis of course of DTG and DTA curves the characteristic temperature points for thermal effects accompanying the thermal decomposition reactions were determined. This results were linked with structural changes occurred in sample. It has been shown that the highest weight loss of the sample at temperatures of about 320°C is associated with destruction of C-H bonds (FTIR). In addition, a large volume of gases and high amounts of compounds from the BTEX group are generated when liquid metal interacts with oil sand. The results show, that compared to other molding sands used in foundry, this material is characterized by the highest gaseous emissions and the highest harmfulness, because benzene emissions per kilogram of oil sand are more than 7 times higher than molding sand with furan and phenolic binders and green sand with bentonite and lustrous carbon carrier.