bluuebunny/crossref_metadata_2025_split huggingface dataset:
What To Do With Lateral Nodal Disease in Low Locally Advanced Rectal Cancer? A Call for Further Reflection and Research
Authors: Kusters Miranda , Slater Andrew , Muirhead Rebecca , Hompes Roel , Guy Richard J. , Jones Oliver M. , George Bruce D. , Lindsey Ian , Mortensen Neil J. , Cunningham Chris 
Published: May 2017

BACKGROUND:
There remains a lack of international consensus on the appropriate management of lateral nodal disease. Although the East manages this more aggressively with lateral lymph node dissections, the West aims to eradicate small-volume disease with neoadjuvant chemoradiotherapy and lateral nodal disease is not considered for routine surgical treatment. However, recent studies have shown that, despite neoadjuvant treatment, a significant number of patients with lateral nodal disease develop local recurrence in the lateral compartment after total mesorectal excision.

OBJECTIVE:
The aim of this study is to assess the role of the pretreatment features of lateral nodes on MRI in regard to local recurrence.

DESIGN:
All patients operated on for low locally advanced rectal cancer over a 5-year period were evaluated retrospectively.

SETTINGS:
This study was conducted at a single expert center.

PATIENTS:
The MRIs of a total of 313 patients were reviewed, and only those with rectal cancers up to 8 cm from the anorectal junction, measured on MRI, were selected. This left 185 patients; of these, 58 patients had clinical T1 or T2 tumors as assessed on MRI, identifying 127 patients who had cT3/T4 tumors that were included in this study.

MAIN OUTCOME MEASURES:
The primary outcomes measured were lateral local recurrence and multivariate analyses.

RESULTS:
The lateral local recurrence rate was significantly higher (33.3% 4-year rate) in patients with nodes larger than 10 mm than in patients with smaller nodes (10.1%, p = 0.03), despite patients being irradiated in the lateral compartment.

LIMITATIONS:
Because this is a relatively uncommon disease, patient numbers are low, and a multicenter study is needed to further address lateral nodal disease in low rectal cancer.

CONCLUSIONS:
Chemoradiotherapy with total mesorectal excision might not be sufficient in a selected group of patients. Further research is needed about which pretreatment features of the lateral nodes predict local recurrence and what is needed to prevent these from developing. See Video Abstract at http://links.lww.com/DCR/A338.
The Rationale for and Reality of the New National Accreditation Program for Rectal Cancer
Authors: Wexner Steven D. , Berho Mariana E. 
Published: May 2017

BACKGROUND:
The treatment of rectal cancer has greatly evolved because of numerous diagnostic and therapeutic advances. More accurate staging by MRI has allowed more appropriate use of neoadjuvant therapy as well as more standardized high-quality total mesorectal excision. Lower rates of perioperative morbidity, permanent colostomy creation, and improved rates of oncologically acceptable rectal excision have led to lower recurrence and greater disease-free survival rates. The recognition of the need for pathologic assessment of the quality of total mesorectal excision, the status of the circumferential resection margins, and the finding of a minimum of 12 lymph nodes as well as identification of extramural vascular invasion has improved staging. These evolutions in imaging, surgical management, and pathologic specimen assessment are interdependent and have been repeatedly shown on national levels to be best operationalized in a multidisciplinary team environment.

OBJECTIVE:
The aim of this article is to evaluate the evidence leading to these important changes, including the imminent launch of the National Accreditation Program for Rectal Cancer.

DESIGN AND SETTING:
Based on the myriad confirmatory experiences in Europe and in the United Kingdom, a multidisciplinary team rectal cancer program was designed by the Consortium for Optimizing Surgical Treatment of Rectal Cancer and subsequently endorsed and accepted by the American College of Surgeons Commission on Cancer.

MAIN OUTCOME MEASURES:
The primary outcome measured is the adherence to the new program standards.

RESULTS:
Surgical treatment of rectal cancer consortium membership rapidly increased from 14 centers in August 2011 to more than 350 centers in April 2017.

LIMITATIONS:
The multidisciplinary team rectal cancer program has not yet launched; thus, its impact cannot yet be assessed.

CONCLUSIONS:
It is our hope and expectation that the outstanding improvement in quality outcomes repeatedly demonstrated within Europe, and extensively shown as much needed in the United States, will be rapidly achieved.
Systematic Review of Animal Models Used in Research of Origins and Treatments of Fecal Incontinence
Authors: Evers Judith , Jones James F. X. , O’Connell P. Ronan 
Published: May 2017

BACKGROUND:
Fecal incontinence is a common disorder, but its pathophysiology is not completely understood.

OBJECTIVE:
The aim of this review is to present animal models that have a place in the study of fecal incontinence.

DATA SOURCES:
A literature review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines performed in August 2016 revealed 50 articles of interest. Search terms included fecal/faecal incontinence and animal model or specific species.

STUDY SELECTION:
Articles not describing an animal model, in vitro studies, veterinary literature, reviews, and non-English articles were excluded.

MAIN OUTCOME MEASURES:
The articles described models in rats (n = 31), dogs (n = 8), rabbits (n = 7), and pigs (n = 4).

RESULTS:
Different fecal incontinence etiologies were modeled, including anal sphincter lesions (33 articles) ranging from a single anal sphincter cut to destruction of 50% of the anal sphincter by sharp dissection, electrocautery, or diathermy. Neuropathic fecal incontinence (12 articles) was achieved by complete or incomplete pudendal, pelvic, or inferior rectal nerve damage. Mixed fecal incontinence (5 articles) was modeled either by the inflation of pelvic balloons or an array of several lesions including nervous and muscular damage. Anal fistulas (2 articles), anal sphincter resection (3 articles), and diabetic neuropathy (2 articles) were studied to a lesser extent.

LIMITATIONS:
Bias may have arisen from the authors’ own work on fecal incontinence and the absence of blinding to the origins of articles.

CONCLUSIONS:
Validated animal models representing the main etiologies of fecal incontinence exist, but no animal model to date represents the whole pathophysiology of fecal incontinence. Therefore, the individual research questions still dictate the choice of model and species.
Physician Burnout and Well-Being: A Systematic Review and Framework for Action
Authors: Rothenberger David A. 
Published: May 2017

BACKGROUND:
Physician burnout in the United States has reached epidemic proportions and is rising rapidly, although burnout in other occupations is stable. Its negative impact is far reaching and includes harm to the burned-out physician, as well as patients, coworkers, family members, close friends, and healthcare organizations.

OBJECTIVE:
The purpose of this review is to provide an accurate, current summary of what is known about physician burnout and to develop a framework to reverse its current negative impact, decrease its prevalence, and implement effective organizational and personal interventions.

DATA SOURCES:
I completed a comprehensive MEDLINE search of the medical literature from January 1, 2000, through December 28, 2016, related to medical student and physician burnout, stress, depression, suicide ideation, suicide, resiliency, wellness, and well-being. In addition, I selectively reviewed secondary articles, books addressing the relevant issues, and oral presentations at national professional meetings since 2013.

STUDY SELECTION:
Healthcare organizations within the United States were studied.

RESULTS:
The literature review is presented in 5 sections covering the basics of defining and measuring burnout; its impact, incidence, and causes; and interventions and remediation strategies.

CONCLUSIONS:
All US medical students, physicians in training, and practicing physicians are at significant risk of burnout. Its prevalence now exceeds 50%. Burnout is the unintended net result of multiple, highly disruptive changes in society at large, the medical profession, and the healthcare system. Both individual and organizational strategies have been only partially successful in mitigating burnout and in developing resiliency and well-being among physicians. Two highly effective strategies are aligning personal and organizational values and enabling physicians to devote 20% of their work activities to the part of their medical practice that is especially meaningful to them. More research is needed.
Effect of N-Desalkylquetiapine/Quetiapine Plasma Level Ratio on Anxiety and Depression in Bipolar Disoder: A Prospective Observational Study
Authors: Rovera Chiara , Mauri Massimo C. , Chiara Di Pace , Paletta Silvia , Reggiori Alessandra , Ciappolino Valentina , Cattaneo Dario , Baldelli Sara , Clementi Emilio , Altamura Alfredo C. 
Published: May 2017

Background:
The aim of this study was to analyze the relationships between quetiapine and N-desalkylquetiapine plasma levels and clinical improvement, particularly, in regard to depressive and anxious symptoms and to hostility.

Methods:
This was a prospective observational study that involved 37 outpatients diagnosed as having bipolar disorder I or II. All the patients were observed during a clinical acute and postacute phase. Patients were prescribed 50–800 mg of quetiapine. Patients were evaluated at baseline, after 15 days and after 3 months using the Brief Psychiatry Rating Scale with particular reference to the dimensions of depression, anxiety, and hostility. The plasma concentrations of quetiapine and N-desalkylquetiapine were determined after 3 months using blood samples taken at steady state.

Results:
There was a significant relationship between the N-desalkylquetiapine/quetiapine ratio and the improvement in the depression dimension, and there was not a significant relationship between the N-desalkylquetiapine/quetiapine ratio and anxiety and hostility improvement. Quetiapine treatment was well tolerated, and there were no extrapyramidal, anticholinergic, or other side effects to note. There was no relationship between plasma quetiapine or N-desalkylquetiapine concentrations and side effects.

Conclusions:
Our findings confirm the efficacy of quetiapine on depressive symptoms, and the available data support that quetiapine's antidepressant activity is mediated by the active metabolite norquetiapine, and it exemplifies the case of an active metabolite that can make a drug like quetiapine originally introduced as an antipsychotic a useful antidepressant agent.
Oral Human Papillomavirus in Women With High-Grade Cervical Intraepithelial Neoplasia
Authors: Woelber Linn , Breuer Julia , Meyer Thomas , Vettorazzi Eik , Prieske Katharina , Bohlmann Inga , Busch Chia-Jung , Teudt Ingo , Brummer Oliver , Mueller Volkmar , Schmalfeldt Barbara , Grimm Donata 
Published: May 2017

ObjectiveThis study was designed to investigate the co-prevalence of cervical and oropharyngeal human papillomavirus (HPV) infection in patients with HPV-related high-grade disease of the uterine cervix (high-grade squamous intraepithelial lesion [HSIL]).Materials and MethodsIn a prospective cohort study, women with abnormal cervical cytology admitted to our colposcopy units received HPV testing of the uterine cervix and the oropharynx via smear. From a subset of patients, oral lavage was collected to compare detection rates of HPV DNA between lavage and swab. Patients with confirmed high-risk HPV (HR-HPV)–positive HSIL of the cervix were further investigated. Sexual behavior and lifestyle factors were documented with a standardized questionnaire.ResultsTwo hundred thirty-five women were included in the study. Of the 235 women, 135 (57.5%) were cervically HR-HPV positive with histologically confirmed high-grade cervical intraepithelial lesion (median [range] age = 30 [21–45] years). Of these, only 6 (4.4%) also had a positive oral specimen. In 3 (50%) of the 6 cases, the same HPV type was detected in oral and cervical samples (HPV 16, 35, and 45). Oral HPV detection was not higher when combining swab and lavage compared with swab alone. A relation between sexual behavior and oral HPV detection could not be demonstrated.ConclusionsOral HPV prevalence in women with cervical HPV infection and HSIL is low. Simultaneous testing of oropharyngeal and cervical HPV infection does not seem promising as future screening strategy.
A Population Pharmacokinetic Analysis to Study the Effect of Therapeutic Hypothermia on Vancomycin Disposition in Children Resuscitated From Cardiac Arrest*
Authors: Zane Nicole R. , Reedy Michael D. , Gastonguay Marc R. , Himebauch Adam S. , Ramsey Evan Z. , Topjian Alexis A. , Zuppa Athena F. 
Published: May 2017

Objectives:
Limited data exist on the effects of therapeutic hypothermia on renal function and pharmacokinetics in pediatric patients after cardiac arrest. The objective was to describe the differences in vancomycin disposition in pediatric patients following cardiac arrest treated with either therapeutic hypothermia or normothermia using population pharmacokinetic modeling.

Design:
Single-center, retrospective cohort study.

Setting:
A tertiary care hospital pediatric and cardiac ICU.

Patients:
Fifty-two pediatric patients (30 d to 17 yr old) who experienced a cardiac arrest, received vancomycin, and were treated with therapeutic hypothermia (32–34°C) or normothermia (36.3–37.6°C) between January 1, 2010, and September 30, 2014, were reviewed.

Interventions:
None.

Measurements and Main Results:
A two-compartment model with linear elimination, weight effects on clearance, intercompartmental clearance (Q), central volume of distribution (V1), and peripheral volume of distribution (V2) adequately described the data despite high variability due to the small sample size. The typical value of clearance in this study was 4.48 L/hr (0.19 L/hr/kg0.75) for a normothermic patient weighing 70 kg and a glomerular filtration rate of 90 mL/min/1.73 m2. Patients treated with normothermia but with reduced or poor renal function (≤ 90 mL/min/1.73 m2) had up to an 80% reduction in vancomycin clearance compared to those with normal renal function (90–140 mL/min/1.73 m2). Patients with normal renal function but treated with therapeutic hypothermia versus normothermia experienced up to 25% reduction in vancomycin clearance. Patients treated with therapeutic hypothermia and with poor renal function experienced up to an 84% reduction in vancomycin clearance.

Conclusions:
Patients receiving hypothermia and/or with decreased renal function had lower vancomycin clearances based on a retrospectively fitted two-compartment model in children who experience cardiac arrest.
Impact of Narrative Expressive Writing on Heart Rate, Heart Rate Variability, and Blood Pressure After Marital Separation
Authors: Bourassa Kyle J. , Allen John J.B. , Mehl Matthias R. , Sbarra David A. 
Published: May 2017

ABSTRACT

Objective
Divorce is a common stressor that is associated with increased risk for poor long-term physical and mental health. Using an experimental design, the current study examined the impact of expressive writing (EW) on average heart rate (HR), HR variability (HRV), and blood pressure (BP) 7.5 months later.

Methods
Participants from a community sample of recently separated adults (N = 109) were assigned to one of three conditions: traditional EW, narrative EW, or a control writing condition, and were assessed three times for an average of 7.5 months. Each study visit included 27 minutes of physiological assessment; the primary outcomes at each assessment were mean-level HR, HRV, BP scores averaged across six different tasks.

Results
Participants in the traditional EW condition did not significantly differ from control participants in their later HR, HRV, or BP. However, relative to control participants, those in the narrative EW condition had significantly lower HR (B = −3.41, 95% confidence interval = −5.76 to −1.06, p = .004) and higher HRV 7.5 months later (B = 0.41, 95% confidence interval = 0.16 to 0.74, p = .001). When comparing narrative EW participants to those in the traditional EW and control writing as a single group, these effects remained and were moderately sized, Cohen d values of −0.61 and 0.60, respectively, and durable across all task conditions when analyzed in independent models. The writing condition groups did not differ in their later BP.

Conclusions
Narrative EW decreased HR and increased HRV after marital separation but did not affect BP. We discuss the possible disconnect between psychology and physiology in response to EW, as well as possible future clinical applications after marital separation.
The Association of Intracranial Vascular Calcification and Stenosis With Acute Ischemic Cerebrovascular Events
Authors: Quiney Brendan , Ying Stephen M. , Hippe Daniel S. , Balu Niranjan , Urdaneta-Moncada Alfonso R. , Mossa-Basha Mahmud 
Published: May 2017

Objective
The aim of this article was to evaluate the association of intracranial artery calcification (IAC) with acute downstream ischemic stroke (dAIS)/transient ischemic attack while considering stenosis.

Methods
Consecutive stroke computed tomography angiography head/neck examinations from January 2010 to April 2010 were reviewed. Per-vessel IAC and stenosis of greater than or equal to 30% were documented by 2 neuroradiologists. Associations between calcification and dAIS were assessed using multivariate logistic regression, controlling for traditional risk factors and stenosis.

Results
A total of 1287 arterial segments from 99 patients were reviewed. Intracranial artery calcification was significantly associated with dAIS (odds ratio [OR], 2.2; P = 0.009). This association persisted among nonstenotic arteries, with significantly higher likelihood of dAIS for arteries with IAC than those without (OR, 2.5; P = 0.009). However, among stenotic arteries, calcified stenoses had a lower association of dAIS than noncalcified stenoses (OR, 0.55; 95% confidence interval, 0.17–1.8; P = 0.33).

Conclusions
Without concurrent stenosis, IAC is a significant risk factor for dAIS. When stenosis is present, IAC does not increase the association with dAIS. Stenotic and nonstenotic calcifications may represent different disease processes, as represented in the histology literature.
MotifMark: Finding Regulatory Motifs in DNA Sequences
Authors: Hassanzadeh Hamid Reza , Kolhe Pushkar , Isbell Charles L. , Wang May D. 
Published: May 2017

AbstractThe interaction between proteins and DNA is a key driving force in a significant number of biological processes such as transcriptional regulation, repair, recombination, splicing, and DNA modification. The identification of DNA-binding sites and the specificity of target proteins in binding to these regions are two important steps in understanding the mechanisms of these biological activities. A number of high-throughput technologies have recently emerged that try to quantify the affinity between proteins and DNA motifs. Despite their success, these technologies have their own limitations and fall short in precise characterization of motifs, and as a result, require further downstream analysis to extract useful and interpretable information from a haystack of noisy and inaccurate data. Here we propose MotifMark, a new algorithm based on graph theory and machine learning, that can find binding sites on candidate probes and rank their specificity in regard to the underlying transcription factor. We developed a pipeline to analyze experimental data derived from compact universal protein binding microarrays and benchmarked it against two of the most accurate motif search methods. Our results indicate that MotifMark can be a viable alternative technique for prediction of motif from protein binding microarrays and possibly other related high-throughput techniques.
CircMarker: A Fast and Accurate Algorithm for Circular RNA Detection
Authors: Li Xin , Chu Chong , Pei Jingwen , Măndoiu Ion , Wu Yufeng 
Published: May 2017

AbstractWhile RNA is often created from linear splicing during transcription, recent studies have found that non-canonical splicing sometimes occurs. Non-canonical splicing joins 3’ and 5’ and forms the socalled circular RNA. It is now believed that circular RNA plays important biological roles such as affecting susceptibility in some diseases. within these few years, several experimental methods have been developed to enrich circular RNA while degrade linear RNA. Although several useful software tools for circRNA detection have been developed as well, these tools may miss many circular RNA. Also, existing tools are slow for large data because those tools often depend on reads mapping. In this paper, we present a new computational approach, named CircMarker, based on k-mers rather than reads mapping for circular RNA detection. CircMarker takes advantage of transcriptome annotation files to create k-mer table for circular RNA detection. Empirical results show that CircMarker outperforms existing tools in circular RNA detection on accuracy and efficiency in many simulated and real datasets. CircMarker can be downloaded fromhttps://github.com/lxwgcool/CircMarker.
Simulating the Dynamics of Targeted Capture Sequencing with CapSim
Authors: Cao Minh Duc , Ganesamoorthy Devika , Coin Lachlan J.M. 
Published: May 2017

AbstractMotivationTargeted sequencing using capture probes has become increasingly popular in clinical applications due to its scalability and cost-effectiveness. The approach also allows for higher sequencing coverage of the targeted regions resulting in better analysis statistical power. However, because of the dynamics of the hybridisation process, it is difficult to evaluate the efficiency of the probe design prior to the experiments which are time consuming and costly.ResultsWe developed CapSim, a software package for simulation of targeted sequencing. Given a genome sequence and a set of probes, CapSim simulates the fragmentation, the dynamics of probe hybridisation, and the sequencing of the captured fragments on Illumina and PacBio sequencing platforms. The simulated data can be used for evaluating the performance of the analysis pipeline, as well as the efficiency of the probe design. Parameters of the various stages in the sequencing process can also be evaluated in order to optimise the efficacy of the experiments.AvailabilityCapSim is publicly available under BSD license athttps://github.com/mdcao/capsim.