bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnosis and management of malignant peripheral nerve sheath tumors: Current practice and future perspectives
Authors: Prudner Bethany C , Ball Tyler , Rathore Richa , Hirbe Angela C 
Published: November 2019

AbstractOne of the most common malignancies affecting adults with the neurofibromatosis type 1 (NF1) cancer predisposition syndrome is the malignant peripheral nerve sheath tumor (MPNST), a highly aggressive sarcoma that typically develops from benign plexiform neurofibromas. Approximately 8–13% of individuals with NF1 will develop MPNST during young adulthood. There are few therapeutic options, and the vast majority of people with these cancers will die within 5 years of diagnosis. Despite efforts to understand the pathogenesis of these aggressive tumors, the overall prognosis remains dismal. This manuscript will review the current understanding of the cellular and molecular progression of MPNST, diagnostic workup of patients with these tumors, current treatment paradigms, and investigational treatment options. Additionally, we highlight novel areas of preclinical research, which may lead to future clinical trials. In summary, MPNST remains a diagnostic and therapeutic challenge, and future work is needed to develop novel and rational combinational therapy for these tumors.
Nitrate Induction of Primary Root Growth Requires Cytokinin Signaling in Arabidopsis thaliana
Authors: Naulin Pamela A , Armijo Grace I , Vega Andrea S , Tamayo Karem P , Gras Diana E , de la Cruz Javiera , Gutiérrez Rodrigo A 
Published: November 2019

AbstractNitrate can act as a potent signal to control growth and development in plants. In this study, we show that nitrate is able to stimulate primary root growth via increased meristem activity and cytokinin signaling. Cytokinin perception and biosynthesis mutants displayed shorter roots as compared with wild-type plants when grown with nitrate as the only nitrogen source. Histological analysis of the root tip revealed decreased cell division and elongation in the cytokinin receptor double mutant ahk2/ahk4 as compared with wild-type plants under a sufficient nitrate regime. Interestingly, a nitrate-dependent root growth arrest was observed between days 5 and 6 after sowing. Wild-type plants were able to recover from this growth arrest, while cytokinin signaling or biosynthesis mutants were not. Transcriptome analysis revealed significant changes in gene expression after, but not before, this transition in contrasting genotypes and nitrate regimes. We identified genes involved in both cell division and elongation as potentially important for primary root growth in response to nitrate. Our results provide evidence linking nitrate and cytokinin signaling for the control of primary root growth in Arabidopsis thaliana.
Efficient root metabolism improves drought resistance of Festuca arundinacea
Authors: Perlikowski Dawid , Augustyniak Adam , Skirycz Aleksandra , Pawłowicz Izabela , Masajada Katarzyna , Michaelis �nne , Kosmala Arkadiusz 
Published: November 2019

AbstractFestuca arundinacea is a model to work on the mechanisms of drought resistance in grasses. The crucial components of that resistance still remain not fully recognized. It was suggested that deep root system could be a crucial trait for drought avoidance strategy but the other components of root performance under water deficit have not paid much attention of scientists. In this study, two genotypes of F. arundinacea with a different ability to withstand soil water deficit were selected to perform comprehensive research, including analysis of root architecture, phytohormones, proteome, primary metabolome and lipidome under progressive stress conditions, followed by a rewatering period. The experiments were performed in tubes, thus enabling undisturbed development of root systems. We demonstrated that long roots are not sufficient to perfectly avoid drought damage in F. arundinacea and to withstand adverse environmental conditions without a disturbed cellular metabolism (with respect to leaf relative water potential and cellular membrane integrity). Furthermore, we proved that metabolic performance of roots is as crucial as its architecture under water deficit, to cope with drought stress via avoidance, tolerance and regeneration strategies. We believe that the presented studies could be a good reference for the other, more applied experiments, in closely related species.
Home Bias and Local Contagion: Evidence from Funds of Hedge Funds
Authors: Sialm Clemens , Sun Zheng , Zheng Lu 
Published: November 2019

AbstractOur paper analyzes the geographical preferences of hedge fund investors and the implication of these preferences for hedge fund performance. We find that funds of hedge funds overweigh their investments in hedge funds located in the same geographical areas and that funds with a stronger local bias exhibit superior performance. Local bias also gives rise to excess flow comovement and extreme return clustering within geographic areas. Overall, our results suggest that while funds of funds benefit from local advantages, their local bias also creates market segmentation that can destabilize the underlying hedge funds.
Teaching Evidence-Based Medicine to Medical Students Using Wikipedia as a Platform
Authors: Murray Heather , Walker Melanie , Dawson Jennifer , Simper Natalie , Maggio Lauren A. 
Published: November 2019

Problem
While ideal curricular structures for effective teaching of evidence-based medicine (EBM) have not been definitively determined, optimal strategies ensure that EBM teaching is interactive and clinically based, aligns with major trends in education and health care, and uses longitudinally integrated, whole-task activities.

Approach
The authors developed a longitudinal, semester-long project, embedded in a first-year medicine course, through which they taught EBM using Wikipedia as a platform. Students worked individually and in small groups to choose a medicine-related Wikipedia article, identify information gaps, search for high-quality resources, appraise the sources, and incorporate the new information into the article (i.e., by editing Wikipedia). Students also applied their new appraisal skills to critique a second article. The authors used an online tool to track and record student editing, and they obtained qualitative data on student perceptions of the project via survey. Duplicate marking of a sample of assignments was performed using the Valid Assessment of Learning in Undergraduate Education critical thinking rubric developed by Finley and Rhodes.

Outcomes
In fall 2017, 101 students made over 1,000 unique edits to 16 online Wikipedia articles, adding over 10,000 words. Through thematic analysis of qualitative data, the authors highlighted several aspects of the project that students appreciated, as well as barriers related to completing their projects. Correlation of the 17 consenting students’ final assignments with the critical thinking rubric supports the assignment structure as a tool for assessing critical thinking.

Next Steps
This authentic task adheres to the principles of high-quality EBM instruction and could be implemented by a variety of health care educational programs. Modifications to the delivery model are underway to address challenges identified.
Internal Medicine Residency Program Directors’ Screening Practices and Perceptions About Recruitment Challenges
Authors: Angus Steven V. , Williams Christopher M. , Stewart Emily A. , Sweet Michelle , Kisielewski Michael , Willett Lisa L. 
Published: November 2019

Purpose
To examine internal medicine residency program directors’ (PDs’) screening practices and perceptions about current recruitment challenges.

Method
In March–May 2017, the Association of Program Directors in Internal Medicine Survey Committee sent a survey to 373 Alliance for Academic Internal Medicine member residency programs. PDs rated the importance of 23 inclusion and 11 exclusion criteria for interview invitation decision making, provided United States Medical Licensing Examination (USMLE) cutoff scores for U.S. medical school and international medical graduates, and indicated changes in recruitment practices due to application inflation, including their ability to conduct holistic review and interest in potential solutions to address application inflation. Exploratory factor analysis was used to identify and confirm factors that were most important to interview invitation decision making.

Results
The response rate for eligible programs was 64% (233/363). USMLE Step 2 Clinical Knowledge scores were the criteria most frequently reported to be “very important” (131/233, 57%). Among respondents who reported any criteria as “very important,” 155/222 (70%) identified a single most important (SMI) criterion. Non-USMLE criteria were frequently reported as an SMI criterion (68%). Concerning exclusion criteria, 157/231 (68%) reported they “absolutely would not invite” applicants with hints of unprofessional behavior. Of the 214/232 (92%) who reported an increase in applications, 138 (64%) adjusted recruitment practices. Respondents were most interested in limiting the number of applications per applicant (163/231, 71%), allowing applicants to indicate high interest in a subset of programs (151/229, 66%), and creating a national database of qualities of matched applicants for each program (121/228, 53%).

Conclusions
PDs rely heavily on USMLE scores when making interview invitation decisions. However, collectively, non-USMLE criteria were more frequently reported as an SMI criterion. Most programs adjusted recruitment practices to respond to application volume. Several potential solutions to address application inflation garnered wide support.
Critical Care Management of Toxicities Associated With Targeted Agents and Immunotherapies for Cancer
Authors: Gutierrez Cristina , McEvoy Colleen , Munshi Laveena , Stephens R. Scott , Detsky Michael E. , Nates Joseph L. , Pastores Stephen M. 
Published: November 2019

Objectives:
To describe the most common serious adverse effects and organ toxicities associated with emerging therapies for cancer that may necessitate admission to the ICU.

Data Sources and Study Selection:
PubMed and Medline search of relevant articles in English on the management of adverse effects of immunotherapy for cancer.

Data Extraction and Data Synthesis:
Targeted therapies including tyrosine kinase inhibitors, monoclonal antibodies, checkpoint inhibitors, and immune effector cell therapy have improved the outcome and quality of life of patients with cancer. However, severe and life-threatening side effects can occur. These toxicities include infusion or hypersensitivity reactions, cytokine release syndrome, pulmonary, cardiac, renal, hepatic, and neurologic toxicities, hemophagocytic lymphohistiocytosis, opportunistic infections, and endocrinopathies. Cytokine release syndrome is the most common serious toxicity after administration of monoclonal antibodies and immune effector cell therapies. Most of the adverse events from immunotherapy results from an exaggerated T-cell response directed against normal tissue, resulting in the generation of high levels of proinflammatory cytokines. Toxicities from targeted therapies are usually secondary to “on target toxicities.” Management is largely supportive and may include discontinuation of the specific agent, corticosteroids, and other immune suppressing agents for severe (grade 3 or 4) immune-related adverse events like neurotoxicity and pneumonitis.

Conclusions:
The complexity of toxicities associated with modern targeted and immunotherapeutic agents for cancer require a multidisciplinary approach among ICU staff, oncologists, and organ specialists and adoption of standardized treatment protocols to ensure the best possible patient outcomes.
Nonparametric Population Pharmacokinetic Modeling of Isoniazid in Colombian Patients With Tuberculosis
Authors: Rodriguez Carlos A. , Zuluaga Andres F. , Neely Michael N. , Sierra Yamile , Morales-Gutierrez Jessica , Zapata Julian , Zapata Juan D. , Naranjo Tonny W. , Agudelo Yuli 
Published: November 2019

Background:
Isoniazid (INH) is a first-line antituberculosis (TB) agent with a pharmacokinetic profile characterized by high interindividual variation; however, population pharmacokinetic studies in patients with TB are scarce. The aim was to develop a population model for INH in Colombian patients with TB suitable for predicting drug exposure and assessing the probability of target attainment of pharmacodynamic goals.

Methods:
Ten hospitalized adult patients with TB undergoing INH treatment were recruited. After an 8-hour fasting, subjects took 300 mg of INH, and 10 samples were taken from 0 to 12 hours. INH was quantified by high-performance liquid chromatography–UV, and data were analyzed with the Pmetrics R package software. A Monte Carlo simulation with the model parameters was run to determine the probability of target attainment for optimal efficacy.

Results:
The best model included 2 compartments, first-order absorption (Ka), delayed absorption (Tlag), and linear clearance (CL). Median Tlag was 0.25 hours, 5.54 hour−1 for Ka,

JOURNAL/thdm/04.03/00007691-201912000-00005/inline-formula1/v/2023-08-14T203520Z/r/image-tiff

for CL,

JOURNAL/thdm/04.03/00007691-201912000-00005/inline-formula2/v/2023-08-14T203520Z/r/image-tiff

for the volume of the central compartment (Vc), 1.04 L/h for intercompartmental clearance (Q), and 788 L for the volume of the peripheral compartment (Vp). CL and Vc were allometrically scaled on basis of the normalized body weight.

Conclusions:
The Monte Carlo simulation indicated that 300 mg of INH per day is appropriate for Mycobacterium tuberculosis strains with minimal inhibitory concentration (MIC) up to 0.03 mg/L (target: area under the concentration–time curve/MIC >597); however, to cover strains with MIC up to 0.125 mg/L (80% of clinical isolates), a dose of 900 mg per day would be required.
Lymphedema Liposuction with Immediate Limb Contouring
Authors: Chen Wei F. , Zeng Wei-Feng , Hawkes Patrick J , Man Jeanette , Bowen Mindy 
Published: November 2019

Background:
Liposuction is the treatment of choice for solid predominant extremity lymphedema. The classic lymphedema liposuction technique does not remove skin excess created following bulk removal. The skin excess is presumed to resolve with spontaneous skin contracture. We investigated the technique of simultaneously performing liposuction with immediate skin excision in patients with solid predominant lymphedema and compared the outcome with that from the classic technique.

Methods:
Modified liposuction with skin excision (mLIPO) and standard liposuction without skin excision (sLIPO) were offered to patients with solid predominant extremity lymphedema. Skin traction of 4 cm and undulating skin mobility constituted positive “flying squirrel” sign. Patients with negative “flying squirrel” sign were excluded. mLIPO patients underwent skin excision. Surgical outcomes and postoperative complications were compared.

Results:
The study enrolled 15 and 26 patients into the sLIPO and mLIPO groups, respectively. mLIPO patients demonstrated statistically significant decrease in seroma/hematoma, contour irregularity, and skin necrosis, while experiencing increased procedural satisfaction.

Conclusions:
Skin excision following liposuction for solid predominant lymphedema is safe. It decreases postoperative complication and improves surgical outcome.
ASSOCIATION OF TREATMENT RESPONSE WITH QUANTITATIVE CHANGES IN CHOROIDAL NEOVASCULARIZATION AND CHOROIDAL VESSEL IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION
Authors: Lee Hyungwoo , Lee Minsub , Kim Myung Ae , Chung Hyewon , Kim Hyung Chan 
Published: November 2019

Purpose:
To evaluate the association between treatment response and quantitative morphological changes in choroidal neovascularization and outer choroidal vessels using optical coherence tomography angiography (OCTA) and en face OCT in neovascular age-related macular degeneration (nAMD).

Methods:
We retrospectively analyzed 75 eyes of typical nAMD patients and 53 polypoidal choroidal vasculopathy eyes of 124 patients with OCTA performed at least 6 months after initial antivascular endothelial growth factor treatment. Quantitative parameters, including vessel area, vessel diameter, branch vessel length, fractal dimension, and lacunarity were analyzed based on en face images of the choroidal neovascularization and choroidal vessel in Haller's layer. Parameters associated with loss of logarithm of the minimum angle of resolution visual acuity with the basis of 0.3 and the treatment interval (good vs. poor responder based on 12 weeks) were analyzed. Analyses were conducted for “before OCTA” (initial visit to OCTA) and “after OCTA” (OCTA to 6 months post-OCTA).

Results:
In typical nAMD, visual acuity loss before OCTA was associated with a higher SD of choroidal neovascularization diameter and lower choroidal fractal dimension. Visual acuity loss after OCTA in typical nAMD was associated with higher lacunarity of the choroid. Poor responders before OCTA were not associated with any factor. Poor responders after OCTA were associated with a lower SD of outer choroidal vessel diameter in typical nAMD. In polypoidal choroidal vasculopathy, no factor was associated with clinical outcomes in either period.

Conclusion:
Quantitative analyses of choroidal neovascularization on OCTA and choroidal vessels on en face OCT provide information about treatment response, including changes in visual acuity and treatment interval, in nAMD.
LATE RECURRENCE OF CHOROIDAL NEOVASCULARIZATION IN PATIENTS WITH MULTIFOCAL CHOROIDITIS: CLINICAL SURVEILLANCE IN PERPETUITY
Authors: Orellana-Rios Jorge , Leong Belinda C. S. , Fernández-Avellaneda Pedro , Gattoussi Sarra , Freund K. Bailey , Yannuzzi Lawrence A. 
Published: November 2019

Purpose:
To report a very late recurrence of choroidal neovascularization (CNV) in elderly patients with noninfectious multifocal choroiditis (MFC).

Methods:
Retrospective case series of patients with MFC with confirmed recurrence of CNV. Choroidal neovascularization was diagnosed with multimodal imaging, including optical coherence tomography angiography. Multifocal choroiditis–associated CNV eyes were treated with intravitreal injections of anti–vascular endothelial growth factor medication.

Results:
Four eyes of three patients were included in our study, with a mean (range) age of 73 years (67–78). The period between the original CNV and the recurrence was 53 years, with a range of 48–60 years. The mean number (range) of injections given after the late recurrence per eye was 7 (5–11). The mean duration (range) of follow-up post-treatment initiation was 93 (40–122) weeks. All eyes improved to 20/30 visual acuity or better at 6 months after initial treatment.

Conclusion:
Patients with MFC are never exempt from recurrent CNV, warranting follow-up in perpetuity. Age-related factors are important to consider which may increase the susceptibility for activating MFC-associated CNV in elderly people. Macular neovascularization could respond to a standard approach to management, in these patients with MFC, by a judicious use of intravitreal injections of anti–vascular endothelial growth factor therapy.
Career Development Training for Interventional Pulmonary Fellows
Authors: Shafiq Majid , Akulian Jason , Desai Neeraj , French Kim , Sachdeva Ashutosh , Lamb Carla , Shojaee Samira , Argento Angela C. , Lee Hans J. 
Published: November 2019

Background:
Interventional pulmonary (IP) fellows spend ≥6 years of postgraduate medical education before IP training. Given the high employment attrition rates of early medical professionals, we investigated the IP fellows’ self-assessed readiness for employment and the role of an intense preemployment educational intervention on improving the same.

Materials and Methods:
Over 2 consecutive academic years, IP fellows nationally were invited to a mid-year career development symposium focusing on employment search strategy and early career development. Attendees were anonymously surveyed presymposium/postsymposium and 6 months later at graduation. Both quantitative and qualitative data were collected. Attendees’ knowledge and skills were rated on a 5-point Likert scale. A control group of IP fellows that did not attend the symposium were also surveyed at graduation.

Results:
In total, 53 of 55 attendees (96% response rate) completed the presymposium survey and 50 of 55 (91%) completed the final survey at graduation. Overall, 16 of 18 (89%) nonattendees also completed the final survey at graduation. IP Fellows reported low baseline self-assessment scores on all question domains. Scores increased significantly postsymposium and were sustained at graduation (P<0.05). At graduation, the average response score of symposium attendees was significantly higher than that of nonattendees (P=0.04). Overall, 84% reported that the symposium helped them with their employment search.

Conclusion:
Advanced IP fellows were not well-equipped for a strategic employment search and early career development at the onset of their IP fellowship training. Participation in an intense educational intervention significantly improved fellows’ self-assessment scores, an effect that was sustained at 6 months.
Clinical Presentation, Management, and Outcomes of Idiopathic Pain in Percutaneous Bone-anchored Hearing Implants
Authors: Caspers Coosje Jacoba Isabella , Nelissen Rik Chrétien , Verhamme Luc Martijn , Meijer Frederick Jan Anton , Mylanus Emmanuel Antonius Maria , Hol Myrthe Karianne Sophie 
Published: November 2019

Objective:
To identify clinical features and investigate treatment outcomes of patients with idiopathic pain related to a percutaneous bone-anchored hearing implant (BAHI) and to propose management recommendations.

Study Design:
Retrospective chart analysis.

Setting:
Tertiary referral center.

Patients:
The clinical data of 14 patients who were treated for idiopathic pain around their percutaneous BAHI between May 2007 and February 2018 at our tertiary referral center were reviewed.

Main Outcome Measures:
Pain after treatment and implant loss.

Results:
All 14 patients received treatment with oral antibiotics. Nine patients received oral antibiotic combination therapy for 4 weeks, whereafter pain resolved in 4. Out of the five other patients, receiving either antibiotic monotherapy or shortened antibiotic combination therapy, pain resolved in two. In case of persistent pain (57.1%) after initial treatment, other pain management therapies were attempted, however all with only limited effect. Six patients (42.8%) underwent elective removal of the implant. In two patients spontaneous implant loss occurred. In two of the four patients who underwent reimplantation, pain relapsed. In one of these, pain resolved after the removal of the new implant. In the other patient, pain persisted, despite abutment removal. With exception of this latter patient, all other 13 patients were pain free at the latest follow-up. Cone beam computed tomography did not offer additional information regarding diagnosis or treatment.

Conclusion:
Idiopathic pain in BAHI is a rare but bothersome symptom which can result in implant removal. After oral antibiotic combination treatment, symptoms resolved in approximately 40% of patients. Therefore, we think conservative treatment with these antibiotics before implant removal surgery, is worth considering.