bluuebunny/crossref_metadata_2025 huggingface dataset:
The MUSE Atlas of Discs (MAD): Ionized gas kinematic maps and an application to diffuse ionized gas
Authors: den Brok Mark , Carollo C Marcella , Erroz-Ferrer Santiago , Fagioli Martina , Brinchmann Jarle , Emsellem Eric , Krajnović Davor , Marino Raffaella A , Onodera Masato , Tacchella Sandro , Weilbacher Peter M , Woo Joanna
Published: November 2019

We have obtained data for 41 star forming galaxies in the MUSE Atlas of Discs (MAD) survey with VLT/MUSE. These data allow us, at high resolution of a few 100 pc, to extract ionized gas kinematics (V, σ) of the centres of nearby star forming galaxies spanning 3  dex in stellar mass. This paper outlines the methodology for measuring the ionized gas kinematics, which we will use in subsequent papers of this survey. We also show how the maps can be used to study the kinematics of diffuse ionized gas for galaxies of various inclinations and masses. Using two different methods to identify the diffuse ionized gas, we measure rotation velocities of this gas for a subsample of six galaxies. We find that the diffuse ionized gas rotates on average slower than the star forming gas with lags of 0–10 km s−1 while also having higher velocity dispersion. The magnitude of these lags is on average 5 km s−1 lower than observed velocity lags between ionized and molecular gas. Using Jeans models to interpret the lags in rotation velocity and the increase in velocity dispersion we show that most of the diffuse ionized gas kinematics are consistent with its emission originating from a somewhat thicker layer than the star forming gas, with a scale height that is lower than that of the stellar disc.
Domestication of High-Copy Transposons Underlays the Wheat Small RNA Response to an Obligate Pathogen
Authors: Poretti Manuel , Praz Coraline Rosalie , Meile Lukas , Kälin Carol , Schaefer Luisa Katharina , Schläfli Michael , Widrig Victoria , Sanchez-Vallet Andrea , Wicker Thomas , Bourras Salim
Published: November 2019

Plant genomes have evolved several evolutionary mechanisms to tolerate and make use of transposable elements (TEs). Of these, transposon domestication into cis-regulatory and microRNA (miRNA) sequences is proposed to contribute to abiotic/biotic stress adaptation in plants. The wheat genome is derived at 85% from TEs, and contains thousands of miniature inverted-repeat transposable elements (MITEs), whose sequences are particularly prone for domestication into miRNA precursors. In this study, we investigate the contribution of TEs to the wheat small RNA immune response to the lineage-specific, obligate powdery mildew pathogen. We show that MITEs of the Mariner superfamily contribute the largest diversity of miRNAs to the wheat immune response. In particular, MITE precursors of miRNAs are wide-spread over the wheat genome, and highly conserved copies are found in the Lr34 and QPm.tut-4A mildew resistance loci. Our work suggests that transposon domestication is an important evolutionary force driving miRNA functional innovation in wheat immunity.
Clinician Knowledge, Attitudes, and Practice Regarding Cannabis: Results from a National Veterans Health Administration Survey
Authors: Kansagara Devan , Morasco Benjamin J , Iacocca Megan O , Bair Matthew J , Hooker Elizabeth R , Becker William C
Published: November 2019

Background

Cannabis is increasingly available and used for medical and recreational purposes, but few studies have assessed provider knowledge, attitudes, and practice regarding cannabis.

Methods

We administered a 47-item electronic survey to assess nationwide Veterans Health Administration (VHA) clinician knowledge, beliefs, attitudes, and practice regarding patients’ use of cannabis.

Results

We received 249 completed surveys from 39 states and the District of Columbia. Fifty-five percent of respondents were female, 74% were white, and the mean age was 50 years. There were knowledge gaps among a substantial minority of respondents in specific areas: terminology, psychoactive effects of cannabis components, VHA policy, and evidence regarding benefits and harms of cannabis. Most respondents were likely or very likely to plan to taper opioids if urine drug testing was positive for tetra-hydro cannabinol (THC; 73%). A significantly greater proportion of respondents from states in which cannabis is illegal for any purpose (odds ratio [OR] = 4.9, 95% confidence interval [CI] = 2.0–10.8) or is recreationally illegal (OR = 5.0, 95% CI = 2.4–10.8) reported being likely or very likely to taper opioids as compared with respondents from states in which cannabis is legal for medical and recreational purposes.

Conclusions

Among the sample, we found knowledge gaps, areas of discomfort discussing key aspects of cannabis use with their patients, and variation in practice regarding opioids in patients also using THC. These results suggest a need for more widespread clinician education about cannabis, as well as an opportunity to develop more robust guidance and evidence regarding management of patients using prescription opioids and cannabis concomitantly.
Evaluating the Uptake and Acceptability of Standardized Postoperative Rehabilitation Guidelines Using an Online Knowledge Translation Approach
Authors: Chepeha Judy C , Silveira Anelise , Sheps David , Beaupre Lauren A ,   Shoulder and Upper Extremity Research Group of Edmonton (SURGE)
Published: November 2019

Background

Providing physical therapists with evidence-based and consensus-derived guidelines to manage postoperative shoulder patients is essential; these guidelines should be readily available and provide clinically applicable information. Knowledge translation (KT) initiatives that encourage interaction between clinicians and researchers, that have multifaceted components and use a variety of strategies, can significantly change practice.

Objective

The objective of this study was to determine the uptake and acceptability of standardized postoperative shoulder guidelines with an accompanying online KT resource through evaluation of website analytics and a quantitative survey.

Design

A multi-pronged approach was used to assess uptake and acceptability of the guidelines and online KT resource.

Methods

Website analytics of usage and geographical location of users was measured as were physical therapist survey responses.

Results

Website analytics revealed that 5406 individuals used the online resource between October 2012 and September 2013 with the average visit lasting 8 minutes; only 47% of users were within the guideline developers’ surgical referral region. Physical therapists who used the new shoulder guidelines were very satisfied or satisfied (96%) with the guidelines, reporting they promoted patient-specific clinical decision-making extremely or very well (68%). They viewed the online KT resource positively, with 79% rating it as “very useful” or “quite useful.” Physical therapists from regions beyond those expected to use the new shoulder guidelines were also aware of the website and also rated it as very useful.

Limitations

The survey sample was relatively small and did not directly assess patient outcomes.

Conclusions

An online KT web resource developed in conjunction with standardized postoperative shoulder guidelines was perceived as useful based on website analytics and survey responses. Active KT strategies such as this can improve uptake and dissemination of best practice in physical therapy.
A Phenotype–Genotype Codon Model for Detecting Adaptive Evolution
Authors: Jones Christopher T , Youssef Noor , Susko Edward , Bielawski Joseph P
Published: November 2019

A central objective in biology is to link adaptive evolution in a gene to structural and/or functional phenotypic novelties. Yet most analytic methods make inferences mainly from either phenotypic data or genetic data alone. A small number of models have been developed to infer correlations between the rate of molecular evolution and changes in a discrete or continuous life history trait. But such correlations are not necessarily evidence of adaptation. Here, we present a novel approach called the phenotype–genotype branch-site model (PG-BSM) designed to detect evidence of adaptive codon evolution associated with discrete-state phenotype evolution. An episode of adaptation is inferred under standard codon substitution models when there is evidence of positive selection in the form of an elevation in the nonsynonymous-to-synonymous rate ratio $\omega$ to a value $\omega > 1$. As it is becoming increasingly clear that $\omega > 1$ can occur without adaptation, the PG-BSM was formulated to infer an instance of adaptive evolution without appealing to evidence of positive selection. The null model makes use of a covarion-like component to account for general heterotachy (i.e., random changes in the evolutionary rate at a site over time). The alternative model employs samples of the phenotypic evolutionary history to test for phenomenological patterns of heterotachy consistent with specific mechanisms of molecular adaptation. These include 1) a persistent increase/decrease in $\omega$ at a site following a change in phenotype (the pattern) consistent with an increase/decrease in the functional importance of the site (the mechanism); and 2) a transient increase in $\omega$ at a site along a branch over which the phenotype changed (the pattern) consistent with a change in the site’s optimal amino acid (the mechanism). Rejection of the null is followed by post hoc analyses to identify sites with strongest evidence for adaptation in association with changes in the phenotype as well as the most likely evolutionary history of the phenotype. Simulation studies based on a novel method for generating mechanistically realistic signatures of molecular adaptation show that the PG-BSM has good statistical properties. Analyses of real alignments show that site patterns identified post hoc are consistent with the specific mechanisms of adaptation included in the alternate model. Further simulation studies show that the covarion-like component of the PG-BSM plays a crucial role in mitigating recently discovered statistical pathologies associated with confounding by accounting for heterotachy-by-any-cause. [Adaptive evolution; branch-site model; confounding; mutation-selection; phenotype–genotype.]
Learning After the Simulation Is Over: The Role of Simulation in Supporting Ongoing Self-Regulated Learning in Practice
Authors: Shariff Farhana , Hatala Rose , Regehr Glenn
Published: November 2019

The complex and dynamic nature of the clinical environment often requires health professionals to assess their own performance, manage their learning, and modify their practices based on self-monitored progress. Self-regulated learning studies suggest that while learners may be capable of such in situ learning, they often need guidance to enact it effectively. In this Perspective, the authors argue that simulation training may be an ideal venue to prepare learners for self-regulated learning in the clinical setting but may not currently be optimally fostering self-regulated learning practices. They point out that current simulation debriefing models emphasize the need to synthesize a set of identified goals for practice change (what behaviors might be modified) but do not address how learners might self-monitor the success of their implementation efforts and modify their learning plans based on this monitoring when back in the clinical setting. The authors describe the current models of simulation-based learning implied in the simulation literature and suggest potential targets in the simulation training process, which might be optimized to allow medical educators to take full advantage of the opportunity simulation provides to support and promote ongoing self-regulated learning in practice.
Effect of fluoroscopically guided corticosteroid injection versus oral nonsteroidal anti-inflammatory drugs for treatment of coccydynia: A randomized, controlled, single-blind study
Authors: Safari Mir Bahram , Tabrizi Ali , Hassani Ebrahim , Nabiyi Farnood , Mohammadi Sedra , Dindarian Sina
Published: November 2019

Background:

Coccydynia is a major cause of coccyx pain that can result in chronic pain as well as reduced functional performance in patients. The aim of this study was to compare the efficacy of fluoroscopically guided corticosteroid injection with an oral nonsteroidal anti-inflammatory drug (NSAID) to relieve coccyx pain.

Methods:

In a clinical trial study, 28 patients with coccydynia who were randomly divided into two groups and matched based on sex, age, and body mass index. One group was treated with celecoxib 200 mg (every 12 hr) for 1 mo along with regular use of a tailbone pillow while sitting on hard surfaces. The second group received local periarticular injection of methylprednisolone acetate 40 mg along with lidocaine 1%, which was fluoroscopically guided. The patients were followed for 4 mo.

Results:

There was a significant difference in pain severity of the patients when compared with their condition at the beginning of the study in each group (P<0.001). The final pain severity of NSAID group and steroid group was 37.9±14.2 mm and 38.7±16.1 mm, respectively, which was not significantly different. Also the trend of pain severity was similar between the two groups.

Conclusions:

Corticosteroid injection for coccydynia treatment at least has the same advantages of oral NSAID medication. Regarding its single-dose administration and reasonable price, it can be considered as an alternative modality in treatment of this disease if the target patient is selected correctly.

Level of Evidence:

Level I.
Current paradigms in the prehospital care of exertional heat illness: A review
Authors: Altman Joshua , Stern Evan , Stern Mori , Prine Bryan , Breuhl Smith Kristy , Smith Michael Seth
Published: November 2019

Exertional heat illness, including muscle cramps, heat syncope, heat exhaustion, and heat stroke, occur each year in athletes and military soldiers. Exertional heat stroke, the most concerning type of exertional heat illness, is a life-threatening condition defined clinically by a core body temperature greater than 104° F (40°C) and central nervous system dysfunction. Heat stroke may lead to multiorgan failure and death and is one of the leading causes of nontraumatic death in athletes participating in outdoor activities. Current recommendations are discussed regarding prehospital and first responder care of exertional heat illness, particularly heat stroke, with an emphasis on rapid recognition, assessment, and implementation of cooling and advanced care strategies. This overview is of particular interest to orthopaedic team physicians who often are first responders on the field.
Perineural Invasion as a Clue to Malignant Behavior in a Dermatofibroma
Authors: Santos-Briz Angel , García-Gavín Juan , Pastushenko Ievgenia , Sayagués José María , Rodríguez-Peralto José Luis , Requena Luis
Published: November 2019

Dermatofibroma (DF) represents one of the most common mesenchymal proliferations of the skin. Their recurrence rate, even when incompletely excised, is very low, whereas the atypical, aneurysmal, and cellular variants have recurrence rates of up to 20% each. Extraordinary rare malignant lesions with metastases to lymph nodes and/or lung have been described. We report a 64-year-old woman with a long history (years) of a skin lesion on her right arm that became painful during the last months. Histologically, it consisted of a conventional cellular DF in which perineural invasion was present. Subsequently, the lesion showed a clinically aggressive course with recurrences, sarcomatous transformation, and pulmonary metastases. Given that no predictive morphological features have been identified to separate classical benign DF from rare metastasizing forms, perineural invasion in an otherwise conventional DF could be a histopathologic clue for an adverse prognosis and should provoke a closer clinical follow-up.
A Comparison of Fat Graft Processing Techniques: Outcomes in 1,158 Procedures in Prosthetic Breast Reconstructions
Authors: Chiu Wen-Kuan , Fracol Megan , Feld Lauren N. , Qiu Cecil S. , Kim John Y.S.
Published: November 2019

Background:

As fat grafting in breast reconstruction evolves, questions of technique and outcomes persist. We compared 2 common fat processing techniques—decantation (DEC) versus closed wash and filtration (CWF)—with regard to outcomes and efficacy.

Methods:

Chart review of a single surgeon experience with breast fat grafting was performed. Data extracted included demographics, technique, complications, graft volume, and revision rates. Secondarily, the timeline of complication profiles was analyzed. Lastly, subgroup analysis of radiated versus nonradiated breast outcomes was performed.

Results:

One thousand one hundred fifty-eight fat grafting procedures were performed on 775 breasts (654 DEC, 504 CWF). Time-to-event analysis for all complications showed no difference between groups. Independent risk factors for fat necrosis included DEC technique, body mass index >30 kg/m2, and fat injection >75 mL. The majority of cases of fat necrosis, cyst/nodule formation, ultrasounds, and biopsies occurred more than 6 months after grafting. Average graft volume was lower in DEC compared with CWF breasts (50.6 versus 105.0 mL, P < 0.01), and more DEC breasts required repeat fat grafting procedures (39.9% versus 29.6%, P < 0.01). Radiated breasts received larger fat graft volume (89.9 versus 72.4 mL, P < 0.01) and required more fat graft procedures (average 1.62 versus 1.47, P < 0.01).

Conclusions:

This study represents the largest series of breast reconstruction fat grafting to date. DEC harvest technique may be a risk factor for fat necrosis, which results in less fat injection and greater need for repeat procedures. Similarly, radiated breasts require larger graft volume and more repeat procedures.
Advanced Ovarian Cancer: Weighing the Risks and Benefits of Surgery
Authors: KUMAR AMANIKA , CLIBY WILLIAM A.
Published: November 2019

Treatment for patients with advanced ovarian cancer includes a combination of platinum-based chemotherapy and maximally cytoreductive surgery. The 2 options for initial treatment include upfront surgery followed by adjuvant chemotherapy or neoadjuvant chemotherapy followed by interval surgery. Deciding between which approach is a on the basis of several factors: (1) resectability of disease; (2) patient factors such as age, albumin, and body mass index; (3) patient wishes; and (4) overall functional status. Research is needed to further refine these approaches and create a patient-focused treatment plan which includes novel factors such as molecular subtype of disease and frailty and sarcopenia.
A novel surgical predictive model for Chinese Crohn's disease patients
Authors: Dong Yuan , Xu Li , Fan Yihong , Xiang Ping , Gao Xuning , Chen Yong , Zhang Wenyu , Ge Qiongxiang
Published: November 2019

Due to the complexity of Crohn's disease (CD), it is difficult to predict disease course with a single stratification factor or biomarker. A logistic regression (LR) model has been proposed by Guizzetti et al to stratify patients with CD-related surgical risk, which could help decision-making on disease treatment. However, there are no reports on relevant studies on Chinese population. The aim of the study is to present and validate a novel surgical predictive model to facilitate therapeutic decision-making for Chinese CD patients. Data was extracted from retrospective full-mode electronic medical records, which contained 239 CD patients and 1524 instances. Two sub-datasets were generated according to different attribute selection strategies, both of which were split into training and testing sets randomly. The imbalanced data in the training sets was addressed by synthetic minority over-sampling technique (SMOTE) algorithm before model development. Seven predictive models were employed using 5 popular machine learning algorithms: random forest (RF), LR, support vector machine (SVM), decision tree (DT) and artificial neural networks (ANN). The performance of each model was evaluated by accuracy, precision, F1-score, true negative (TN) rate, and the area under the receiver operating characteristic curve (AuROC). The result revealed that RF outperformed all other baseline models on both sub-datasets. The 10 leading risk factors for CD-related surgery returned from RF for attribute ranking were changes of radiology, presence of a fistula, presence of an abscess, no infliximab use, enteroscopy findings, C-reactive protein, abdominal pain, white blood cells, erythrocyte sedimentation rate and platelet count. The proposed machine learning model can accurately predict the risk of surgical intervention in Chinese CD patients, which could be used to tailor and modify the treatment strategies for CD patients in clinical practice.
The efficacy of dexketoprofen for migraine attack
Authors: Yang Baohua , Xu Zhili , Chen Linglong , Chen Xinguo , Xie Yuequn
Published: November 2019

Background:

The efficacy of dexketoprofen for migraine attack remains controversial. We conduct a systematic review and meta-analysis to explore the influence of dexketoprofen supplementation versus placebo on pain control in migraine attack patients.

Methods:

We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through March 2019 for randomized controlled trials (RCTs) assessing the effect of dexketoprofen supplementation versus placebo on pain control for migraine attack patients. This meta-analysis is performed using the random-effect model.

Results:

Five RCTs involving 794 patients are included in the meta-analysis. Overall, compared with control group for migraine attack, dexketoprofen supplementation is associated with substantially increased pain free at 2 hours (RR = 1.90; 95% CI = 1.43–2.53; P < .0001), pain free at 48 hours (RR = 1.63; 95% CI = 1.07–2.49; P = .02), good or excellent treatment (RR = 1.48; 95% CI = 1.24–1.78; P < .0001) and pain relief at 2 hours (RR = 1.80; 95% CI = 1.17–2.77; P = .007), as well as reduced need for rescue drug (RR = 0.64; 95% CI = 0.43–0.94; P = .02), with no significant increase in adverse events (RR = 1.51; 95% CI = 0.87–2.62; P = .14).

Conclusion:

Dexketoprofen supplementation benefits to improve pain control at 48 hours and reduce the need for rescue drug in migraine attack patients.
Nursing care in anti-N-methyl-d-aspartate receptor encephalitis
Authors: Yang Li , Jiang Qian , Guan Hongzhi , Bo Haixin
Published: November 2019

Anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is a paraneoplastic limbic encephalitis, recently identified.

To summarize our experience in the nursing care of patients with anti-NMDAR encephalitis managed with surgery and pharmacotherapy.

This study included 45 patients treated between July 2015 and November 2016. Laparoscopic oophorocystectomy was performed in 11 female patients with teratomas. Eleven patients required tracheal intubation or tracheotomy and ventilation.

The patients were hospitalized for an average of 25.2 days. The mental and neurological symptoms were significantly relieved 23.6 ± 4.8 days after surgery or immunotherapy. Near-normal function was restored in 11 patients, while 34 patients had varying degrees of dysfunction at discharge. After follow-up of 1 to 18 months, 24 patients were found to have permanent impairments.

Appropriate symptomatic nursing care is required to ensure the safety of patients with anti-NMDAR encephalitis.
Repair of a defect in the cervical trachea with thyroid-pericardium flap
Authors: Xie Hui , Zhang Yuqian , Yu Fenglei , Wang Xiang
Published: November 2019

Rationale:

Primary end-to-end anastomosis is common in adult trachea resection. Nevertheless, considering that the utilization of grafts is still essential for restoring defect in long-segment tracheal resection surgery, long-segment tracheal resection and reconstruction still remain challenging. Herein we present a novel case in which we resected a large tracheal mass and reconstructed the long-segment defect through using a thyroid-pericardium flap, which has not been reported yet.

Patient concerns:

A 35-year old male patient was admitted due to ‘Repeated dry cough for 2 years, shortness of breath after activities for 1 month’. Patient had no other obvious symptoms.

Diagnoses:

CT revealed that a large neoplasm was located in the cervical trachea and the pedicle was in the tracheal membrane, with total length of approximately 6 cm. Positron emission tomography computed tomography demonstrated an abnormally elevated levels of glucose metabolism in the upper part of the posterior tracheal wall. Therefore, this lesion was primarily considered as a malignancy.

Interventions:

The patient was performed by a primary resection of long-segment tracheal mass followed by thyroid-pericardium composite tissue flap for reconstruction.

Outcome:

The operation was successful, without hydrops or pneumatosis in the mediastinum. One week postoperatively, CT showed that there was no pneumomediastinum and mediastinal abscess. Three weeks postoperatively, fiber bronchoscope showed the flap with normal color and the unobstructed tracheal cavity. The patient healed without complication.

Lessons:

The thyroid-pericardium flap is a convenient, secure, and effective material for long-segment trachea mass resection and reconstruction.
Predictors affecting anterolateral thigh flap in reconstruction of upper extremity
Authors: Li Di , Long Feng , Lei Ming
Published: November 2019

Our study is aim to explore predictors for failure of anterolateral thigh (ALT) flap in the reconstruction of upper extremity.

We performed a retrospective study for 509 patients who underwent ALT flap in the reconstruction of upper extremity. Among them, 27 patients suffered from necrosis of ALT flap (necrosis group, NG) and 482 gained survival of this flap (survival group, SG). We collected possible factors including 3 aspects: demographic variables – age, sex, body mass index (BMI), history of hypertension, diabetes, heart disease, smoking and alcohol, trauma mechanism, and postmenopausal; surgical-related variables – surgical duration, blood loss, number of reconstructed veins, flap size, perforator type, diameter of perforator, and vein graft; blooding variables – hemoglobin, D-dimer, white blood cell, red blood cell, and platelet count (PLT). We compared the above data between NG and SG by univariate, multivariate, and Kaplan–Meier method coupled with a log-rank test linear regression analysis.

The survival incidence of ALT flap repairing upper extremity was 94.7% (482 of 509). The outcome of univariate analysis showed that age (53.5 ± 9.2), BMI (26.7 ± 4.5), larger flap size (24.3∗9.2), D-dimer (0.58 ± 0.10), and PLT (278.1 ± 34.4) in NG were significantly higher than these (44.2 ± 7.9, 22.3 ± 4.2, 19.1∗7.9, 0.48 ± 0.08, 236.6 ± 30.5) in SG. However, diameter of perforator (1.07 ± 0.02) in NG was markedly smaller than that (1.12 ± 0.02) in SG. Additionally, female patients, postmenopausal, patients with using venous stapler or 1 reconstructed vein had a higher failure rate. Multivariate and Kaplan–Meier method implied the same results.

In summary, many factors were related with failure of ALT in the reconstruction of upper extremity. Postmenopausal, D-dimer, and PLT were the first considered as risk factors for ALT flap repairing upper extremity.
Neuropathic painful complications due to endopelvic nerve lesions after robot-assisted laparoscopic prostatectomy
Authors: Cascella Marco , Quarto Giuseppe , Grimaldi Giovanni , Izzo Alessandro , Muscariello Raffaele , Castaldo Luigi , Di Caprio Barbara , Bimonte Sabrina , Del Prete Paola , Cuomo Arturo , Perdonà Sisto
Published: November 2019

Rationale:

Robot-assisted laparoscopic prostatectomy (RALP) is the most frequent strategy used for the surgical remedy of patients with localized prostate cancer. Although there is awareness about potential patient positioning nerve injuries, iatrogenic nerve lesions are less described in the literature. Here, we report 3 cases of patients who presented with neuropathic painful complications due to RALP-associated nerve lesions.

Patient concerns:

A 62-year-old patient (case 1), a 72-year-old male (case 2), and a 57-year-old patient (case 3) presented at the clinic with symptoms of neuropathic pain after RALP surgery.

Diagnosis:

Patients were diagnosed with a potential injury of different branches of the pudendal nerve (cases 1 and 2), and left obturator nerve (case 3).

Interventions:

Patients underwent multimodal pharmacologic treatment through pregabalin, weak opioids, strong opioid, paracetamol, and adjuvants. In cases 2 and 3, a multidisciplinary approach was needed. As the patients responded to conservative treatment, invasive approaches were not necessary.

Outcomes:

After treatment, the patients of case 1 showed pain relief after 4 days, paresthesia resolved in 15 days, whereas the anal crushing sensation lasted for approximately 1 month. In case 2, after 4 weeks of treatment, the patient experienced a considerable decrement in pain intensity with complete response after 4 months. In case 3, pain relief was achieved after 2 days, motor symptoms recovery after 2 weeks, and neuropathic features resolved completely after 5 weeks although the obturator sign resolved within 2 months.

Lessons:

The RALP-associated neurologic injuries may occur even when performed by highly experienced surgeons. A better understanding of the potential iatrogenic nerve lesions can surely allow an improvement in the surgical technique. A multidisciplinary approach and early multimodal pain strategy are mandatory for managing these complications.
Prognostic significance of KIF2A and KIF20A expression in human cancer
Authors: Li Xing , Shu Kunpeng , Wang Zhifeng , Ding Degang
Published: November 2019

Background:

The kinesin family (KIF) is reported to be aberrantly expressed and significantly correlated with survival outcomes in patients with various cancers. This meta-analysis was carried out to quantitatively evaluate the prognostic values of partial KIF members in cancer patients.

Methods:

Two well-known KIF members, KIF2A and KIF20A, were investigated to evaluate their potential values as novel prognostic biomarkers in human cancer. A comprehensive literature search was carried out of the PubMed, EMBASE, Cochrane Library, and Web of Science databases up to April 2019. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association of KIF2A and KIF20A expression with overall survival (OS) and clinicopathological parameters.

Results:

Twenty-five studies involving 7262 patients were finally incorporated, including nine about KIF2A and sixteen about KIF20A. Our results indicated that patients with high expression of KIF2 and KIF20A tended to have shorter OS than those with low expression (HR = 2.23, 95% CI = 1.87–2.65, P < .001; HR = 1.77, 95% CI = 1.57–1.99, P < .001, respectively). Moreover, high expression of these 2 KIF members was significantly associated with advanced clinical stage (OR = 1.98, 95% CI: 1.57–2.50, P < .001; OR = 2.63, 95% CI: 2.03–3.41, P < .001, respectively), positive lymph node metastasis (OR = 2.32, 95% CI: 1.65–3.27, P < .001; OR = 2.13, 95% CI: 1.59–2.83, P < .001, respectively), and distant metastasis (OR = 2.20, 95% CI: 1.21–3.99, P = .010; OR = 5.25, 95% CI: 2.82–9.77, P < .001, respectively); only high KIF20A expression was related to poor differentiation grade (OR = 1.82, 95% CI: 1.09–3.07, P = .023).

Conclusions:

High expression of KIF2 and KIF20A in human cancer was significantly correlated with worse prognosis and unfavorable clinicopathological features, suggesting that these 2 KIF members can be used as prognostic biomarkers for different types of tumors. PROSPERO REGISTRATION NUMBER: CRD42019134928.
Pediatric CNS Tumor Patients Have Significantly Lower Requirement of Tissue Plasminogen Activator for Episodes of Central Venous Catheter Dysfunction Compared With Other Pediatric Oncology Patients: Results of a Population-based Cohort Study
Authors: Howie Chelsea , Crooks Bruce , Moorehead Paul , Kulkarni Ketan
Published: November 2019

Purpose:

Central venous catheters (CVCs) are an important component of care delivery in pediatric oncology patients. However, CVC dysfunction is a common problem. Tissue plasminogen activator (tPA) is often administered to re-establish function, however, specific experience in pediatric patients with central nervous system (CNS) tumors is lacking. The goal of this study was to investigate the CVC experience and use of tPA for episodes of CVC dysfunction in pediatric patients with CNS tumors in comparison with other patients.

Methods:

Medical records of all pediatric oncology patients from the 4 Atlantic provinces in Canada (Nova Scotia, New Brunswick, Prince Edward Island, and Newfoundland and Labrador) were reviewed. Data collected included demographics, treatment, details of CVCs along with CVC dysfunction, and tPA use.

Results:

The cohort consisted of 1152 pediatric oncology patients, 222 (19.3%) of whom had CNS tumors. CVC dysfunction requiring tPA administration occurred in 12 (5.4%) of patients with CNS tumors compared with 182 (19.6%) of patients with non-CNS tumors (P=0.0001). Multivariate logistic regression analysis showed that administration of tPA for CVC dysfunction was 2.5 times more likely in patients with non-CNS tumors than those with CNS tumors (P=0.012; 95% confidence interval, 1.3-4.9).

Conclusions:

Our study showed that pediatric patients with CNS tumors require significantly less frequent administration of tPA for episodes of CVC dysfunction than patients with non-CNS tumors after adjusting for confounding factors. Hypotheses for this include: potential biologic differences of tumors, the role of the blood-brain barrier, or systematic differences in intensity of treatments.
Leading Effectively Through Change
Authors: Lal M. Maureen
Published: November 2019

The pace of change in today's healthcare environment is unprecedented. What used to happen every few months now seems to happen every day. From rapidly shifting technology to evolving models of care to new payment systems, nursing leaders must navigate constant change to stay relevant. How well they manage it has a direct bearing on everything from patient safety and outcomes to nursing cohesion and satisfaction. In this month's Magnet® Perspectives column, we explore the essential elements that contribute to successful change management and the strategies leaders can employ to keep their nurses, and their organizations, forward-focused. In addition, we take a deep dive into the Magnet Model component of transformational leadership and examine its impact on creating and sustaining an environment where change flourishes and nurses thrive.
Developing a Research Friendly Hospital-Based Environment
Authors: Clements-Hickman Alyssa L. , Wilson Jazmine , Wright Lonnie , Davies Claire C.
Published: November 2019

Magnet® designation requires that nurses be actively involved in activities that lead to obtaining evidence through conducting research. Unfortunately, several barriers limit nurses' ability to engage in research activities, including insufficient resources. This article explains how a community-based hospital implemented a fellowship model to circumvent some of these barriers. Two fellowship positions are described, 1 in research and 1 in library sciences. The method, outcomes, and cost of the fellowship model are discussed.
Behavioral Disorders of Preschool Children With Non-Syndromic Craniosynostosis
Authors: Moreno-Villagómez Julieta , Yáñez-Téllez Ma. Guillermina , Prieto-Corona Belén , Seubert-Ravelo Ana Natalia , García Antonio
Published: November 2019

Craniosynostosis is the premature closure of one or more cranial sutures that results in an abnormal skull shape. This condition has been associated with cognitive problems of different levels of severity in all developmental stages in a substantial percentage of children. However, the study of behavioral problems related to this condition has been scarce. The objective of this study was to determine if a sample of Mexican preschoolers with non-syndromic craniosynostosis had more clinical and adaptive behavioral problems than those of their peers. We assessed the behavior of 24 participants between 3 and 5 years of age with non-syndromic craniosynostosis as well as those of 27 healthy children. We used the Behavioral Assessment System for Children (BASC) parent's questionnaire. There were no significant differences between groups for any of the BASC scales, although a small proportion of children from both groups had high, clinically significant, scores on some of the Clinical, Adaptive and Global scales. While the relationship between craniosynostosis and behavioral problems is not clear, it is important to continue to assess conduct at several ages to detect possible problems that could be overlooked by the developmental characteristics during the preschool stage.
Comparative Performance and Neuropathologic Validation of the AD8 Dementia Screening Instrument
Authors: Morris Gabriela M. , Holden Timothy R. , Weng Hua , Xiong Chengjie , Coble Dean W. , Cairns Nigel J. , Morris John C.
Published: November 2019

Background/Objective:

The AD8 informant-based screening instrument has been validated with molecular biomarkers of Alzheimer disease (AD) but not with the gold standard of neuropathologic AD. The objective of this study was to validate the AD8 with neuropathologic AD and compare its predictive performance with that of the Mini-Mental State Examination and both participant-derived and informant-derived subjective memory complaint (SMC) regarding the participant.

Methods:

This longitudinal cohort study at the Knight Alzheimer Disease Research Center at Washington University included 230 participants, ages 50 to 91 years, who later had a neuropathologic examination. Four dementia screening instruments from their baseline assessment were evaluated: the AD8, Mini-Mental State Examination, participant SMC, and informant SMC. The primary outcome was a neuropathologic diagnosis of AD.

Results:

The average participant age at baseline was 80.4 years, 48% were female. All 4 dementia screening tests were predictive of neuropathologic AD. There was no significant difference in the predictive performance of the AD8 compared with the other instruments, but the AD8 had superior sensitivity and combined positive and negative predictive values.

Conclusion:

The AD8 is a brief and sensitive screening instrument that may facilitate earlier and more accurate AD diagnosis in a variety of care settings.
Deep Discriminative Fine-Tuning for Cancer Type Classification
Authors: Harley Alena
Published: November 2019

Determining the primary site of origin for metastatic tumors is one of the open problems in cancer care because the efficacy of treatment often depends on the cancer tissue of origin. Classification methods that can leverage tumor genomic data and predict the site of origin are therefore of great value.

Because tumor DNA point mutation data is very sparse, only limited accuracy (64.5% for 12 tumor classes) was previously demonstrated by methods that rely on point mutations as features (1). Tumor classification accuracy can be greatly improved (to over 90% for 33 classes) by relying on gene expression data (2). However, this additional data is often not readily available in clinical setting, because point mutations are better profiled and targeted by clinical mutational profiling.

Here we sought to develop an accurate deep transfer learning and fine-tuning method for tumor sub-type classification, where predicted class is indicative of the primary site of origin. Our method significantly outperforms the state-of-the-art for tumor classification using DNA point mutations, reducing the error by more than 30% at the same time discriminating over many more classes on The Cancer Genome Atlas (TCGA) dataset. Using our method, we achieve state-of-the-art tumor type classification accuracy of 78.3% for 29 tumor classes relying on DNA point mutations in the tumor only.
Effects of temperature of plant cultivation on plant palatability modify species response to novel climate
Authors: Dostálek Tomáš , Rokaya Maan Bahadur , Münzbergová Zuzana
Published: November 2019

Climate warming is expected to strengthen the plant-herbivore interactions and thus increase the plant consumption rate. However, indirect impacts of temperature (acting via changes in host plant quality) on herbivore performance have only rarely been studied, and therefore, the net effect of temperature change is difficult to predict. We thus tested the effects of temperature on plant palatability and assessed whether the effects can be explained by changes in leaf traits.

We conducted multi-choice feeding experiments with six species of the genusImpatienscultivated at three different temperatures in the growth chambers and in the experimental garden and also studied changes in leaf morphology and chemistry.

The leaves ofImpatiensspecies were most eaten when cultivated in the temperature predicted by climate warming scenario. We found the traits related to leaf morphology (SLA, LDMC and leaf size) partly mediated the effects of temperature on leaf herbivore damage. Herbivores preferred smaller leaves with lower SLA and higher LDMC values. Results of our study suggested that elevated temperature will lead to change in leaf traits and increase their palatability. This will further enhance the levels of herbivory caused by increased herbivore pressure under climate warming.
The genome of the zoonotic malaria parasite Plasmodium simium reveals adaptations to host-switching
Authors: Mourier Tobias , de Alvarenga Denise Anete Madureira , Kaushik Abhinav , de Pina-Costa Anielle , Douvropoulou Olga , Guan Qingtian , Guzmán-Vega Francisco J. , Forrester Sarah , de Abreu Filipe Vieira Santos , Júnior Cesare Bianco , de Souza Junior Julio Cesar , Moreira Silvia Bahadian , Hirano Zelinda Maria Braga , Pissinatti Alcides , de Fátima Ferreira-da-Cruz Maria , de Oliveira Ricardo Lourenço , Arold Stefan T. , Jeffares Daniel C. , Brasil Patrícia , de Brito Cristiana Ferreira Alves , Culleton Richard , Daniel-Ribeiro Cláudio Tadeu , Pain Arnab
Published: November 2019

Background

Plasmodium simium, a malaria parasite of non-human primates (NHP) was recently shown to cause zoonotic infections in humans in Brazil. We sequenced the P. simium genome to investigate its evolutionary history and to identify any genetic adaptions that may underlie the ability of this parasite to switch between host species.

Results

Phylogenetic analyses based on whole genome sequences of P. simium from humans and NHPs reveals that P. simium is monophyletic within the broader diversity of South American Plasmodium vivax, suggesting P. simium first infected NHPs as a result of a host-switch of P. vivax from humans. The P. simium isolates show the closest relationship to Mexican P. vivax isolates. Analysis of erythrocyte invasion genes reveals differences between P. vivax and P. simium, including large deletions in the Duffy Binding Protein 1 (DBP1) and Reticulocyte Binding Protein 2a genes of P. simium. Analysis of P. simium isolated from NHPs and humans revealed a deletion of 38 amino acids in DBP1 present in all human-derived isolates, whereas NHP isolates were multi-allelic.

Conclusions

Analysis of the P. simium genome confirmed a close phylogenetic relationship between P. simium and P. vivax, and suggests a very recent American origin for P. simium. The presence of the DBP1 deletion in all human-derived isolates tested suggests that this deletion, in combination with other genetic changes in P. simium, may facilitate the invasion of human red blood cells and may explain, at least in part, the basis of the recent zoonotic infections.
A Novel Process Maintaining Glycerophospholipid Homeostasis in Mammalian Cells
Authors: Hermansson Martin , Hänninen Satu , Kjellberg Matti , Somerharju Pentti
Published: November 2019

Glycerophospholipid (GPL) homeostasis in eukaryotic cells is thought to be maintained via biosynthesis, degradation and acyl chain remodeling. Here we provide evidence for an additional process termed “head-group remodeling” where other GPLs, when in excess, are rapidly converted to phosphatidylcholine and triacylglycerol. Mass spectrometric studies showed the formation of diacylglycerol, but not phosphatidic acid, from the exogenous GPL thus indicating that the first step is catalyzed by a phospholipase C-type enzyme. Consistently, triacylglycerol formation was significantly inhibited by the knock-down of several PLCs, but not phospholipase Ds. Second, we found that each exogenous GPL strongly inhibited the synthesis of the corresponding endogenous GPL class. Based on these and previous data we hypothesize how mammalian cells could coordinate the multiple processes contributing to GPL homeostasis in mammalian cells. In conclusion, this study provides the first evidence that head group remodeling plays an important role in GPL homeostasis in mammalian cells.
Structural basis for COMPASS recognition of an H2B-ubiquitinated nucleosome
Authors: Worden Evan J. , Zhang Xiangbin , Wolberger Cynthia
Published: November 2019

Methylation of histone H3K4 is a hallmark of actively transcribed genes that depends on mono-ubiquitination of histone H2B (H2B-Ub). H3K4 methylation in yeast is catalyzed by Set1, the methyltransferase subunit of COMPASS. We report here the cryo-EM structure of a six-protein core COMPASS subcomplex, which can methylate H3K4 and be stimulated by H2B-Ub, bound to a ubiquitinated nucleosome. Our structure shows that COMPASS spans the face of the nucleosome, recognizing ubiquitin on one face of the nucleosome and methylating H3 on the opposing face. As compared to the structure of the isolated core complex, Set1 undergoes multiple structural rearrangements to cement interactions with the nucleosome and with ubiquitin. The critical Set1 RxR motif adopts a helix that mediates bridging contacts between the nucleosome, ubiquitin and COMPASS. The structure provides a framework for understanding mechanisms of trans-histone cross-talk and the dynamic role of H2B ubiquitination in stimulating histone methylation.
Targeting cellular DNA damage responses in cancer: Anin vitro-calibrated agent-based model simulating monolayer and spheroid treatment responses to ATR-inhibiting drugs
Authors: Hamis Sara , Yates James , Chaplain Mark AJ , Powathil Gibin G
Published: November 2019

We combine a systems pharmacology approach with an agent-based modelling approach to simulate LoVo cells subjected to AZD6738, an ATR (ataxia telangiectasia mutated and rad3-related kinase) inhibiting anti-cancer drug that can hinder tumour proliferation by targeting cellular DNA damage responses. The agent-based model used in this study is governed by a set of empirically observable rules. By adjusting only the rules when moving between monolayer and multi-cellular tumour spheroid simulations, whilst keeping the fundamental mathematical model and parameters intact, the agent-based model is first parameterised by monolayerin vitrodata and is thereafter used to simulate treatment responses inin vitrotumour spheroids subjected to dynamic drug delivery. Spheroid simulations are subsequently compared toin vivodata from xenografts in mice. The spheroid simulations are able to capture the dynamics ofin vivotumour growth and regression for approximately eight days post tumour injection.

Translating quantitative information betweenin vitroandin vivoresearch remains a scientifically and financially challenging step in preclinical drug development processes. However, well-developed insilicotools can be used to facilitate this invitroto in vivo translation, and in this article we exemplify how data-driven, agent-based models can be used to bridge the gap betweenin vitroandin vivoresearch. We further highlight how agent-based models, that are currently underutilised in pharmaceutical contexts, can be used in preclinical drug development.