bluuebunny/crossref_metadata_2025_split huggingface dataset:
Varieties of involution monoids with extreme properties
Authors: Lee Edmond W H 
Published: January 2019

Abstract
A variety that contains continuum many subvarieties is said to be huge. A sufficient condition is established under which an involution monoid generates a variety that is huge by virtue of its lattice of subvarieties order-embedding the power set lattice of the positive integers. Based on this result, several examples of finite involution monoids with extreme varietal properties are exhibited. These examples—all first of their kinds—include the following: finite involution monoids that generate huge varieties but whose reduct monoids generate Cross varieties; two finite involution monoids sharing a common reduct monoid such that one generates a huge, non-finitely based variety while the other generates a Cross variety; and two finite involution monoids that generate Cross varieties, the join of which is huge.
Medical School Strategies to Address Student Well-Being: A National Survey
Authors: Dyrbye Liselotte N. , Sciolla Andres F. , Dekhtyar Michael , Rajasekaran Senthil , Allgood J. Aaron , Rea Margaret , Knight Allison P. , Haywood Antwione , Smith Stephen , Stephens Mark B. 
Published: January 2019

Purpose
To describe the breadth of strategies U.S. medical schools use to promote medical student well-being.

Method
In October 2016, 32 U.S. medical schools were surveyed about their student well-being initiatives, resources, and infrastructure; grading in preclinical courses; and learning communities.

Results
Twenty-seven schools (84%) responded. Sixteen (59%) had a student well-being curriculum, with content scheduled during regular curricular hours at most (13/16; 81%). These sessions were held at least monthly (12/16; 75%), and there was a combination of optional and mandatory attendance (9/16; 56%). Most responding schools offered a variety of emotional/spiritual, physical, financial, and social well-being activities. Nearly one-quarter had a specific well-being competency (6/27; 22%). Most schools relied on participation rates (26/27; 96%) and student satisfaction (22/27; 81%) to evaluate effectiveness. Sixteen (59%) assessed student well-being from survey data, and 7 (26%) offered students access to self-assessment tools. Other common elements included an individual dedicated to overseeing student well-being (22/27; 82%), a student well-being committee (22/27; 82%), pass/fail grading in preclinical courses (20/27; 74%), and the presence of learning communities (22/27; 81%).

Conclusions
Schools have implemented a broad range of well-being curricula and activities intended to promote self-care, reduce stress, and build social support for medical students, with variable resources, infrastructure, and evaluation. Implementing dedicated well-being competencies and rigorously evaluating their impact would help ensure appropriate allocation of time and resources and determine if well-being strategies are making a difference. Strengthening evaluation is an important next step in alleviating learner distress and ultimately improving student well-being.
Understanding the Effects of General Anesthetics on Cortical Network Activity Using Ex Vivo Preparations
Authors: Voss Logan J. , García Paul S. , Hentschke Harald , Banks Matthew I. 
Published: January 2019

Abstract
General anesthetics have been used to ablate consciousness during surgery for more than 150 yr. Despite significant advances in our understanding of their molecular-level pharmacologic effects, comparatively little is known about how anesthetics alter brain dynamics to cause unconsciousness. Consequently, while anesthesia practice is now routine and safe, there are many vagaries that remain unexplained. In this paper, the authors review the evidence that cortical network activity is particularly sensitive to general anesthetics, and suggest that disruption to communication in, and/or among, cortical brain regions is a common mechanism of anesthesia that ultimately produces loss of consciousness. The authors review data from acute brain slices and organotypic cultures showing that anesthetics with differing molecular mechanisms of action share in common the ability to impair neurophysiologic communication. While many questions remain, together, ex vivo and in vivo investigations suggest that a unified understanding of both clinical anesthesia and the neural basis of consciousness is attainable.
Human Milk and Infants With Congenital Heart Disease
Authors: Davis Jessica A. , Spatz Diane L. 
Published: January 2019

Background:
Human milk is a life-saving medical intervention. Infants with congenital heart disease are at an increased risk for necrotizing enterocolitis, chylothorax, feeding difficulties, and growth failure. In the absence of evidence-based care, their mothers are also at risk for low milk supply and/or poor breastfeeding outcomes.

Purpose:
Summarize the role of human milk and clinical outcomes for infants with congenital heart disease (CHD). Summarize methods of ideal breastfeeding support.

Methods/Search Strategy:
PubMed, Cochrane Library, and CINAHL were the databases used. The terms used for the search related to CHD and necrotizing enterocolitis were “human milk” and “necrotizing enterocolitis” and “congenital heart disease.” This resulted in a total of 17 publications for review.

Findings:
Infants receiving exclusive human milk diet are at a lower risk for necrotizing enterocolitis and will have improved weight gain. Infants with chylothorax who receive skimmed human milk have higher weight-for-age scores than formula-fed infants. Maternal breastfeeding education correlates with decreased risk of poor breastfeeding outcomes.

Implications for Practice:
Human milk is the ideal source of nutrition for infants with CHD and should be encouraged by the care team. Evidence-based lactation education and care must be provided to mothers and families prenatally and continue throughout the infant's hospitalization. If a mother's goal is to directly breastfeed, this should be facilitated during the infant's hospital stay.

Implications for Research:
Evaluate the role between human milk and the incidence of necrotizing enterocolitis, feeding difficulties, and clinical outcomes in the population of infants with CHD.
Friberg Equation to Predict Pediatric Distal Forearm Fracture Remodeling
Authors: Pearce Stephanie S. , Honeycutt Michael W. , Cutchen William A. , Tillman Mark D. , Nimityongskul Prasit 
Published: January 2019

Background:
This study is the first to test Friberg’s equation’s (Vt
=V
0[e
(−ßt)]) accuracy in predicting the residual angular deformity in pediatric distal forearm fractures.

Methods:
Angular deformities from distal forearm fractures in 50 children (mean age, 9 y) were retrospectively measured on follow-up radiographs once healed and compared to extrapolated angles at respective follow-up intervals from 2013 to 2015.

Results:
The predicted and actual angulations from 120 radiographs (mean follow-up, 3mo) showed that the mean predicted angle was similar to the measured angle in the radioulnar plane and only 2 degrees greater than the measured angle in the dorsovolar plane. A strong correlation was observed between predicted and measured angles in both planes.

Conclusions:
Friberg’s equation is a valid tool for predicting remodeling potential in pediatric distal 25% forearm fractures.

Level of Evidence:
Prognostic Study—Level II.
Intensivists in U.S. Acute Care Hospitals*
Authors: Halpern Neil A. , Tan Kay See , DeWitt Meghan , Pastores Stephen M. 
Published: January 2019

Objectives:
To determine the total numbers of privileged and full-time equivalent intensivists in acute care hospitals with intensivists and compare the characteristics of hospitals with and without intensivists.

Design:
Retrospective analysis of the American Hospital Association Annual Survey Database (Fiscal Year 2015).

Setting:
Two-thousand eight-hundred fourteen acute care hospitals with ICU beds.

Patients:
None.

Interventions:
None.

Measurements and Main Results:
Of the 2,814 acute care hospitals studied, 1,469 (52%) had intensivists and 1,345 (48%) had no intensivists. There were 28,808 privileged and 19,996 full-time equivalent intensivists in the 1,469 hospitals with intensivists. In these hospitals, the median (25–75th percentile) numbers of privileged and full-time equivalent intensivists were 11 (5–24) and 7 (2–17), respectively. Compared with hospitals without intensivists, hospitals with privileged intensivists were primarily located in metropolitan areas (91% vs 50%; p < 0.001) and at the aggregate level had nearly thrice the number of hospital beds (403,522 [75%] vs 137,146 [25%]), 3.6 times the number of ICU beds (74,222 [78%] vs 20,615 [22%]), and almost twice as many ICUs (3,383 [65%] vs 1,846 [35%]). At the hospital level, hospitals with privileged intensivists had significantly more hospital beds (median, 213 vs 68; p < 0.0001), ICU beds (median, 32 vs 8; p < 0.0001), a higher ratio of ICU to hospital beds (15.6% vs 12.6%; p < 0.0001), and a higher number of ICUs per hospital (2 vs 1; p < 0.0001) than hospitals without intensivists.

Conclusions:
Analyzing the intensivist section of the American Hospital Association Annual Survey database is a novel approach to estimating the numbers of privileged and full-time equivalent intensivists in acute care hospitals with ICU beds in the United States. This methodology opens the door to an enhanced understanding of the current supply and distribution of intensivists as well as future research into the intensivist workforce.
New perspectives in Merkel cell carcinoma
Authors: del Marmol Véronique , Lebbé Celeste 
Published: January 2019

Purpose of review
Merkel cell carcinoma (MCC), a rapidly progressing skin cancer, has poor prognosis. We reviewed the epidemiology, pathogenesis, diagnosis and treatment of MCC, with a focus on recent therapeutic advancements.

Recent findings
Risk factors for MCC, such as old age, immunosuppression, polyomavirus infection and exposure to UV radiation have already been identified, but the underlying mechanisms leading to carcinogenesis still need clarification. On the basis of recent advances, immunotherapy – in particular, inhibition targeting the programmed cell death protein 1/programmed death-ligand 1 (PD1)/PDL1) immune checkpoint blockade – is currently being investigated in the treatment of metastatic MCC. Avelumab, an anti-PDL1 antibody, was the first drug to be approved internationally as second-line monotherapy for patients with advanced MCC, based on results from the JAVELIN Merkel 200 clinical trial. Avelumab has also recently been approved as first-line treatment for advanced MCC in Europe. Pembrolizumab (anti-PD1) in first-line and nivolumab (anti-PD1) in first-line and second-line treatments are two other checkpoint inhibitors that are under investigation, and showing promising results. New innovative therapies are also in development.

Summary
New insights concerning advances in MCC diagnosis and treatment have been highlighted. Immunotherapy for metastatic MCC constitutes a recent breakthrough in an unmet medical need, but alternative therapies should continue to be investigated.
Changes in Pharmacists' Perceptions After a Training in Opioid Misuse and Accidental Overdose Prevention
Authors: Eukel Heidi N. , Skoy Elizabeth , Werremeyer Amy , Burck Siri , Strand Mark 
Published: January 2019

Introduction:
Continuing education is needed for health professionals to take an active role in reversing the opioid crisis. This report describes the results of training to promote behavioral change by altering pharmacists' perceptions toward opioid misuse through the provision of content-related education.

Methods:
A free 3-hour opioid misuse and overdose prevention training program was developed and delivered to 43 community pharmacists. The training consisted of five modules addressing the disease of addiction, risks associated with opioids and accidental overdose, the role of naloxone, opioid dispensing and consultation pearls, and effective ways to communicate with patients about opioids. A paired analysis was performed from a 12-item survey delivered before and after the training program to assess changes in pharmacists' perception.

Results:
Five items showed a statistically significant (P < .05) change in perceptions after the training. Significant changes were reported for opioid addiction being outside the control of the affected person, the role of family history in prescription drug abuse, the value of counseling to support patients at risk of prescription opioid abuse, the value of screening tools, and the importance of viewing things from the patient's perspective. Correlation analysis identified that pharmacists' views on their role in the fight against the opioid epidemic and their agreement in the value to screen for opioid misuse were most closely related to the desire for behavioral change.

Discussion:
A training program influenced pharmacists' attitudes and perceptions about targeted behaviors and associated with the value of screening for opioid misuse or overdose risk and counseling patients about the benefits and risks of opioids.
Frequent TLE1 Expression in Cutaneous Neoplasms
Authors: Xiong Yiqin , Dresser Karen , Cornejo Kristine M. 
Published: January 2019

Abstract:
TLE1 immunohistochemistry is widely used as a biomarker for synovial sarcoma. Recently, we identified TLE1 expression in a subset of melanomas and noted staining in sebaceous glands and follicular epithelium. TLE1 immunohistochemistry has not been well studied in cutaneous tumors. The aim was to investigate TLE1 expression in sebaceous neoplasms, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC) to determine whether the staining patterns may aid in the diagnosis or classification of these neoplasms. TLE1 immunohistochemistry was performed on sebaceous adenoma (n = 26), sebaceoma (n = 10), sebaceous carcinoma (n = 19), BCC (n = 20), and SCC (n = 19). Positivity was defined as dark-brown nuclear staining and graded as 3+ (strong staining of >50% of cells at 4×), 2+ (moderate staining of 10–50% of cells at 4× or >50% of cells staining at 10×), and 1+ (weak staining of <50% of cells at 10×). No staining was scored as 0. A score of 2–3+ was considered positive and 0–1+ negative. Nuclear TLE1 expression was identified in 25/26 (96%) sebaceous adenomas, 8/10 (80%) sebaceomas, and 17/19 (90%) sebaceous carcinomas. TLE1 also labeled 19/20 (95%) BCCs and 12/19 (63%) SCCs. TLE1 immunohistochemistry frequently highlights sebaceous neoplasms, BCC, and SCC with a fairly high sensitivity (63%–96%). Therefore, TLE1 is not a specific biomarker for synovial sarcoma and should be evaluated with caution, particularly in cases in which the differential diagnosis may include other cutaneous tumors. In addition, TLE1 does not seem to be useful in the diagnosis or classification of these neoplasms.
Pharmacokinetic Variability and Clinical Use of Lacosamide in Children and Adolescents in Denmark and Norway
Authors: Larsen Burns Margrete , Nikanorova Marina , Baftiu Arton , Borg Rasmussen Jan , Johannessen Svein I. , Johannessen Landmark Cecilie 
Published: January 2019

Background:
The indication for the antiepileptic drug lacosamide (LCM) was recently extended to include children from the age of 4 years. Real-life data on the use and serum concentrations of LCM in children and adolescents are limited. The purpose of this study was to investigate the use of LCM in this patient group in relation to age, comedication, dose, serum concentrations and duration of treatment, and to examine pharmacokinetic variability.

Methods:
Children and adolescents (<18 years) who had serum concentrations of LCM measured from January 2012 to June 2018 were retrospectively identified from the therapeutic drug monitoring databases at 2 national epilepsy centers in Norway and Denmark. Clinical data were collected from request forms and medical records.

Results:
Data from 124 patients were included, 61 girls/63 boys. Weight was available for 76 patients. Median age was 15 years (range 2–17 years), dose of LCM 300 mg/d (76–600 mg/d), and serum concentration 18 µmol/L (5–138 µmol/L) [4.5 mg/L (1.3–34.5 mg/L)]. Pharmacokinetic variability was demonstrated as the concentration/(dose/kg) ratio ranged from 1.3 to 9.4 (µmol/L)/(mg/kg) and was affected by age. Polytherapy with 1–3 other antiepileptic drugs was noted in 107 patients (86%). Treatment was continued beyond 1 year in 71% (n = 45) of the 63 patients where such information was available, and all of these 45 patients had serum concentrations within the defined reference range. The 1-year retention rate was higher in patients not concomitantly using other sodium channel–blocking drugs (82% versus 56%).

Conclusions:
The study demonstrates pharmacokinetic variability in and between age groups, which indicates usefulness of therapeutic drug monitoring. More than two-thirds of patients continued treatment beyond 1 year, suggesting reasonable effectiveness.
LC-MS/MS-Based Quantification of 9 Antiepileptic Drugs From a Dried Sample Spot Device
Authors: D'Urso Annachiara , Cangemi Giuliana , Barco Sebastiano , Striano Pasquale , D'Avolio Antonio , de Grazia Ugo 
Published: January 2019

Background:
Therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) is commonly performed on plasma or serum. The use of dried plasma spots (DPSs) could represent a useful tool to facilitate sample shipment to reference laboratories. In this article, the authors describe the application of a commercially available UHPLC-MS/MS method for the determination of 9 commonly prescribed AEDs (levetiracetam, lacosamide, topiramate, ethosuximide, lamotrigine, rufinamide, zonisamide, primidone, and oxcarbazepine and its active metabolite 10-OH-monohydroxycarbazepine) to DPS collected on dried sample spot devices (DSSDs).

Method:
Fifty microliters of plasma were spotted on DSSD. After being air-dried at room temperature, they were extracted using an organic extraction solution containing the appropriate deuterated internal standards. The chromatographic separation was performed on a UHPLC reversed-phase C-18 column, and the analytes were quantified using a triple quadrupole mass spectrometer (LC-MS/MS).

Results:
The assay was linear over the concentration ranges tested with a total runtime of 10.3 minutes. Recovery ranged from 93.7% to 106.8%. Intraday and interday precision for all quality control levels, including lower limit of quantification, ranged from 2.1% to 18.4% and 2.1% to 13.2%. Intraday and interday accuracy biases ranged from −11.7% to 14.3% and −9.2% to 8.0%. The absence of matrix effects was also tested and confirmed. Real samples derived from patients under therapy were also analyzed, and the comparison of results obtained from DSSD with those obtained from plasma showed that the 2 matrices were interchangeable. Stability tests performed on both quality controls, and real samples demonstrated that DSSDs can be easily stored and shipped at room temperature for 15 days.

Conclusions:
The application of the LC-MS/MS method allowed the authors to obtain a very specific, sensitive, and rapid (total runtime = 10.3 minutes) quantification of 9 AEDs starting from very low volumes of plasma samples. The main advantage of DPS over wet samples is room temperature storage and shipment, which lowers shipment costs and makes it suitable for routine TDM. Moreover, in comparison with other alternative matrices, DPS allows for the use of the same therapeutic ranges on which routine TDM is based. DPS on DSSD can thus be considered as a useful and cheap tool for the broader application of TDM.
Myeloid‐Derived Suppressor Cells in Hematologic Diseases: Promising Biomarkers and Treatment Targets
Authors: Bizymi Nikoleta , Bjelica Sunčica , Kittang Astrid Olsnes , Mojsilovic Slavko , Velegraki Maria , Pontikoglou Charalampos , Roussel Mikael , Ersvær Elisabeth , Santibañez Juan Francisco , Lipoldová Marie , Papadaki Helen A. 
Published: January 2019

AbstractMyeloid‐derived suppressor cells (MDSC) are a heterogeneous group of immature myeloid cells that exist at very low numbers in healthy subjects but can expand significantly in malignant, infectious, and chronic inflammatory diseases. These cells are characterized as early‐MDSCs, monocytic‐MDSCs, and polymorphonuclear‐MDSCs and can be studied on the basis of their immunophenotypic characteristics and their functional properties to suppress T‐cell activation and proliferation. MDSCs have emerged as important contributors to tumor expansion and chronic inflammation progression by inducing immunosuppressive mechanisms, angiogenesis and drug resistance. Most experimental and clinical studies concerning MDSCs have been mainly focused on solid tumors. In recent years, however, the implication of MDSCs in the immune dysregulation associated with hematologic malignancies, immune‐mediated cytopenias and allogeneic hemopoietic stem cell transplantation has been documented and the potential role of these cells as biomarkers and therapeutic targets has started to attract a particular interest in hematology. The elucidation of the molecular and signaling pathways associated with the generation, expansion and function of MDSCs in malignant and immune‐mediated hematologic diseases and the clarification of mechanisms related to the circulation and the crosstalk of MDSCs with malignant cells and other components of the immune system are anticipated to lead to novel therapeutic strategies. This review summarizes all available evidence on the implication of MDSCs in hematologic diseases highlighting the challenges and perspectives arising from this novel field of research.
Surgical Corneal Anatomy in Deep Anterior Lamellar Keratoplasty: Suggestion of New Acronyms
Authors: Sarnicola Enrica , Sarnicola Caterina , Cheung Albert Y. , Holland Edward J. , Sarnicola Vincenzo 
Published: January 2019

Abstract:
Deep anterior lamellar keratoplasty (DALK) is the ideal surgery for corneal stromal diseases with a healthy endothelium. This technique offers substantial advantages compared with penetrating keratoplasty, primarily the avoidance of endothelial rejection and longer graft survival. Several DALK techniques have been described and classified into 2 categories, descemetic DALK (dDALK) and predescemetic DALK (pdDALK) depending on whether Descemet membrane-endothelium was thought to be exposed or minimal residual stroma was left behind. This classification was crucial to identify the conditions to achieve good visual outcomes with pdDALK techniques. The recent description of Dua's layer, also known as the pre-Descemet layer, has demonstrated that a very thin layer of stroma exists in some instances where Descemet membrane was thought to be completely exposed. This concept has generated a discrepancy between the previous and current applications of the terms “dDALK” and “pdDALK.” We offer a summary of the published literature and a proposal for a new and more appropriate DALK nomenclature. We suggest adding the terms subtotal anterior lamellar keratoplasty (STALK) and total anterior lamellar keratoplasty (TALK).