bluuebunny/crossref_metadata_2025 huggingface dataset:
Completing the Basic and Clinical Science Course as a First-Year Ophthalmology Resident
Authors: Oke Isdin , Siegel Nicole H. , Peeler Crandall E. , Ness Steven D. , Ramsey Jean E.
Published: January 2020

Background The Basic and Clinical Science Course (BCSC) is the primary educational curriculum for ophthalmology resident physicians in the United States. The Ophthalmic Knowledge Assessment Program (OKAP) examination is an annual evaluation completed by residents that is based primarily on the BCSC curriculum. First-year ophthalmology residents are encouraged to complete the 13 volume BCSC series in preparation for the OKAP examination while balancing a steep clinical learning curve and substantial call schedule. By calculating the daily time commitment necessary to read each volume in the series, we hope to help residents create a realistic study plan to compete the entire BSCS series before the OKAP examination.

Methods We determine the word counts of each volume using an electronic copy of the 2018–2019 BCSC series. We include all text sections and legends, and we exclude all figures and tables. We calculate the time per day of dedicated reading required to complete a goal number of BCSC books between the start of ophthalmology residency (postgraduate year 2 [PGY2]) and the OKAP examination by developing a formula that is a function of self-assessed reading speed.

Results A first-year ophthalmology (PGY2) resident with an average reading speed of 250 words per minute must read for 25.0 minutes per day to complete the entire BCSC series before the OKAP examination. If studying is initiated at the beginning of intern (PGY1) year, the resident must read for 10.2 minutes per day. We introduce a formula and provide a table to guide residents on the amount of time needed to dedicate to reading the BCSC each day as a function of self-assessed reading speed.

Discussion Completion of all volumes of the BCSC requires a daily commitment with little room for missed sessions. The commitment is substantially more realistic if initiated during the PGY1 year; thus, residency programs should encourage an early start to OKAP preparation. We hope with a better understanding of the daily time commitment involved in completing the BCSC series, ophthalmology residents will be able to develop more successful study plans.
The Distance between Tibial Tubercle and Trochlear Groove Correlates with Knee Articular Torsion
Authors: Barahona Maximiliano , Guzmán Mauricio , Barrientos Cristian , Zamorano Álvaro , Palet Miguel , Hinzpeter Jaime ,   Collaborating Authors
Published: January 2020

This study aims to correlate the tibial tubercle to trochlear groove (TT-TG) distance with knee axial alignment. The hypothesis is that as internal torsion of the distal femur or external torsion of the proximal tibial increases, the TT-TG distance increases. We designed a cross-sectional study approved by our institutional ethics review board. We reviewed 32 computed tomography angiographies of patients that have nonjoint or bone-related symptoms. Distal femoral torsion, proximal tibial torsion, knee articular torsion (AT), and TT-TG distance were measured. A regression analysis between the TT-TG distance and the AT was performed. A positive correlation between the TT-TG distance and the AT was found. An increase in external torsion of the proximal tibial or an increase in internal torsion of the distal femur increases the TT-TG distance. For a correct interpretation of the TT to trochlear groove distance, we propose that the axial alignment should be included in the regular analysis of patellofemoral disease.
Utility of Platelet Function Tests: A Recent Review Round Up
Authors: Sharan Sandeep , Gandhi Ajay , Kapoor Poonam Malhotra
Published: January 2020

Patients undergoing cardiac surgery are at risk of excessive bleeding and associated complications. Excessive bleeding during and after cardiac surgery has an incidence of ~20%. Massive bleeding and subsequent requirement for blood product administration and mediastinal re-exploration is associated with significant morbidity and mortality. Postoperative, nonsurgical bleeding in cardiac surgical patients is often multifactorial. Platelet dysfunction, excessive fibrinolysis, hypothermia, preoperative anemia, and deficiency of coagulation factors or their dilution are all suggested etiologies of postoperative bleeding. Among these, the most important is thought to be platelet dysfunction, which occurs as a result of the interplay of acquired and pharmacologically induced factors. Patients suffering from coronary artery disease are usually advised to stop antiplatelet medication a few days prior to coronary artery bypass grafting (CABG) to reduce the incidence of postoperative bleeding. However, patients who are still on antiplatelet drugs are at an increased risk of postoperative bleeding. Currently, the transfusion of blood and blood components to manage postoperative bleeding after CABG remains largely empirical, with considerable variation among institutions. Algorithm-based hemostatic therapy has been shown to be superior to empiric hemostatic therapy that is based on clinical judgment. Hence, there is a need to have objective tests to demonstrate platelet dysfunction before platelet transfusion. Several devices of platelet function tests have been reported in clinical studies to evaluate platelet dysfunction and quantify the need for antiplatelet therapy
Associations between Maternal Lipid Profiles and Pregnancy Complications: A Prospective Population-Based Study
Authors: Zhang Yiqi , Lan Xi , Cai Congjie , Li Run , Gao Yan , Yang Liuqing , Wu Cheng , Dong Hongli , Pang Xinxin , Bai Dan , Zeng Guo
Published: January 2020

Objective To investigate whether plasma lipid profiles are independently associated with pregnancy complications including gestational diabetes mellitus (GDM), hypertensive disorder complicating pregnancy (HDCP), and intrahepatic cholestasis of pregnancy (ICP).

Study Design A prospective study was conducted among 1,704 pregnant women at three medical institutions in Chengdu, China. The concentrations of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured at gestational weeks 12 ± 1, 24 ± 1, and 34 ± 1. Logistic regression models were used to estimate the association between lipid profiles and pregnancy complications. Receiver operating characteristic analysis was performed to determine the value of lipid profiles to predict GDM and HDCP.

Results After adjusting for potential confounders, TG, TC, and LDL-C in the first trimester were independently associated with GDM (TG: odds ratio [OR] =2.00, 95% confidence interval [CI]: 1.57–2.56; TC: OR = 1.38, 95% CI: 1.16–1.64; LDL-C: OR = 1.43, 95% CI: 1.14–1.79) and HDCP (TG: OR = 2.42, 95% CI: 1.56–3.78, TC: OR = 1.64, 95% CI: 1.04–2.57; LDL-C: OR = 1.87, 95% CI: 1.07–3.25). The TC concentration during the whole pregnancy (first trimester: OR = 1.53, 95% CI: 1.13–2.08; second trimester: OR = 1.31, 95% CI: 1.06–1.61; third trimester: OR = 1.39, 95% CI: 1.17–2.04) and LDL-C in the last two trimesters (second trimester: OR = 1.62, 95% CI: 1.30–2.04; third trimester: OR = 1.56, 95% CI: 1.29–1.88) were positively associated with ICP. HDL-C in the third trimester was negatively associated with the risk of ICP (OR = 0.46, 95% CI: 0.22–0.98). Combining lipid profiles in the first trimester with the other common predictors to predict GDM or HDCP owned stronger predictive power with the largest area under the curve (GDM: 0.643 [95% CI: 0.613–0.673], HDCP: 0.707 [95% CI: 0.610–0.804]) than either indicator alone.

Conclusion Maternal lipid profiles during the whole pregnancy are significantly associated with GDM, HDCP, and ICP. Combining lipid profiles in the first trimester with the other common predictors could effectively improve the power of predicting GDM and HDCP.
Suppression and saturation of error field-driven tearing mode for different magnetic shears in rotating plasmas
Authors: Zhang Bang-Feng , Wang Xian-Qu
Published: January 2020

Effects of the equilibrium plasma flow on the error field-driven tearing mode are investigated in a two-dimensional resistive magnetohydrodynamics model. It is found that nonlinear suppression of the tearing mode is dominated by the interaction between the magnetic island and the error field rather than the local flow shear on rational surfaces. For a small magnetic shear case, a modest rigid flow can counteract the driving effect of the error field on the mode in the early nonlinear growth stage and transform the error field-driven mode to a general tearing mode. For a large magnetic shear case, after a fast linear growth, the tearing mode will enter a saturated process quickly before the locked mode occurs, and the mode saturation level is reduced due to the magnetic island and error field pushing each other. The threshold flow strength and its scaling analysis for the saturated modes are also given in this paper.
Study on the blood flow in stenosed microvascular model under pulsed magnetic field
Authors: Mok Jinwon , Han Seonghyun , Lee Hyunsook
Published: January 2020

It is widely known that abnormal peripheral blood circulation due to intravascular stenosis causes ischemic diseases and blood circulatory disorders. The purpose of this study was to investigate the influence of pulsed magnetic field (PMF) on hemodynamic characteristics in blood vessel with stenosis of 33% with diameter of 15μm, with the change of PMF intensity and hematocrit (Ht) concentration. Stenosed microvascular channels were fabricated using polydimethylsiloxane (PDMS). Our PMF stimulator has the maximum intensity of 2700G at a transition time of 102 μs with pulse intervals of 1Hz. For the Ht altered RBCs suspension, the changes in blood flow and deformation of red blood cells (RBCs) were examined before and after PMF stimulus with various intensity of 200∼2700G. In stenosed channel, threshold intensity for improvement of blood flow seems to be 400G. The higher the Ht, the higher the viscosity and the slower the velocity of RBCs, but after PMF stimulus, RBCs movement overall increased by more than 9∼67% in both Ht 5% and 20% RBCs suspension. Our study shows that PMF plays an important role in in treating cardiovascular diseases with blood circulation disorders caused by narrowing microvascular due to stenosis. In order to extend our results to clinical applications, we need develop more indicators for hemorheologic characteristics such as viscosity and resistance, and need further experiment with diverse PMF condition such as pulse shape, pulse duration, or repetition rate.
Development of an automatic magnetic immunostaining system for rapid intraoperative diagnosis of cancer metastasis
Authors: Sekino Masaki , Kuwahata Akihiro , Yoshibe Akinobu , Imai Kiyotaka , Kaneko Miki , Chikaki Shinichi , Saito Itsuro , Tsuruma Akinori , Sakamoto Satoshi , Handa Hiroshi , Matsuda Sachiko , Kusakabe Moriaki
Published: January 2020

Magnetic immunostaining provides a novel technique for rapid intraoperative diagnosis of cancer metastasis and its characteristics in lymph nodes. Previous studies have shown the effectiveness of this technique using the manual staining process. However, to make this technique feasible for use in hospitals, establishing an automatic process is important. Thus, the objective of this study is to realize a device for immunostaining using magnetic fields that could not only automatically stain the samples, but also wash the specimen and change experimental solutions as well. The specifications for our prototype device were determined based on the manually performed experiments. We successfully fabricated a prototype device and demonstrated automatic immunostaining using it. The device completed, within 10 minutes, processes of blocking the specimen, injection of the magnetic beads, antigen-antibody reaction, and washing out the beads. The reaction took 1 minute, which was significantly shorter than that of conventional immunostaining. The device is expected to provide improved reproducibility of staining because of its automated processes.
Reevaluating teacher evaluations in higher education
Authors: Feder Toni
Published: January 2020

Relying on students to rate professors is convenient, cheap, and problematic.
Johannes Kepler’s pursuit of harmony
Authors: Rothman Aviva
Published: January 2020

The great astronomer linked the speed of planetary orbits to musical scales—and to the harmonious interaction of humans on Earth during a time of religious warfare.
Creating an Age-Friendly Public Health System
Authors: De Biasi Anne , Wolfe Megan , Carmody Jane , Fulmer Terry , Auerbach John
Published: January 2020

Background and Objectives

The public health system in America—at all levels—has relatively few specialized initiatives that prioritize the health and well-being of older adults. And when public health does address the needs of older adults, it is often as an afterthought. In consultation with leaders in public health, health care, and aging, an innovative Framework for an Age-Friendly Public Health System (Framework) was developed outlining roles that public health could fulfill, in collaboration with aging services, to address the challenges and opportunities of an aging society.

Research Design and Methods

With leadership from Trust for America’s Health and The John A. Hartford Foundation, the Florida Departments of Health and Elder Affairs are piloting the implementation of this Framework within Florida’s county health departments and at the state level. The county health departments are expanding data collection efforts to identify older adult needs, creating new alliances with aging sector partners, coordinating with other agencies and community organizations to implement evidence-based programs and policies that address priority needs, and aligning efforts with the age-friendly communities and age-friendly health systems movements.

Results, and Discussion and Implications

The county health departments in Florida participating in the pilot are leveraging the Framework to expand public health practice, programs, and policies that address health services and health behaviors, social, and economic factors and environmental conditions that allow older adults to age in place and live healthier and more productive lives. The model being piloted in Florida can be tailored to meet the unique needs of each community and their older adult population.
The Sex of History, or Object/Matters
Authors: Arondekar Anjali
Published: January 2020

The mandate to think of Stonewall as a global historical event within South Asia necessitates a difficult act of translation. Was my goal as a historian of sexuality and South Asia to decentre the primacy of Stonewall with local historical events of import? Or was it more epistemological, to address instead the question of why historical causality and memorialization works differently within the fabular geography that is South Asia? In other words, did the history of the Stonewall riots create more of a political demand on subaltern collectivities to ‘produce’ their own seismic historical event, or did it foreground even further the epistemological divide between the West and the Rest? This brief essay is a meditation on these questions and more.
Polygenetic Risk Scores for Major Psychiatric Disorders Among Schizophrenia Patients, Their First-Degree Relatives, and Healthy Participants
Authors: Ohi Kazutaka , Nishizawa Daisuke , Shimada Takamitsu , Kataoka Yuzuru , Hasegawa Junko , Shioiri Toshiki , Kawasaki Yasuhiro , Hashimoto Ryota , Ikeda Kazutaka
Published: January 2020

Background

The genetic etiology of schizophrenia (SCZ) overlaps with that of other major psychiatric disorders in samples of European ancestry. The present study investigated transethnic polygenetic features shared between Japanese SCZ or their unaffected first-degree relatives and European patients with major psychiatric disorders by conducting polygenic risk score (PRS) analyses.

Methods

To calculate PRSs for 5 psychiatric disorders (SCZ, bipolar disorder [BIP], major depressive disorder, autism spectrum disorder, and attention-deficit/hyperactivity disorder) and PRSs differentiating SCZ from BIP, we utilized large-scale European genome-wide association study (GWAS) datasets as discovery samples. PRSs derived from these GWASs were calculated for 335 Japanese target participants [SCZ patients, FRs, and healthy controls (HCs)]. We took these PRSs based on GWASs of European psychiatric disorders and investigated their effect on risk in Japanese SCZ patients and unaffected first-degree relatives.

Results

The PRSs obtained from European SCZ and BIP patients were higher in Japanese SCZ patients than in HCs. Furthermore, PRSs differentiating SCZ patients from European BIP patients were higher in Japanese SCZ patients than in HCs. Interestingly, PRSs related to European autism spectrum disorder were lower in Japanese first-degree relatives than in HCs or SCZ patients. The PRSs of autism spectrum disorder were positively correlated with a young onset age of SCZ.

Conclusions

These findings suggest that polygenic factors related to European SCZ and BIP and the polygenic components differentiating SCZ from BIP can transethnically contribute to SCZ risk in Japanese people. Furthermore, we suggest that reduced levels of an ASD-related genetic factor in unaffected first-degree relatives may help protect against SCZ development.
Degenerate elliptic equations for resonant wave problems
Authors: Nicolopoulos Anouk , Campos Pinto Martin , Després Bruno , Ciarlet Patrick
Published: January 2020

The modelling of resonant waves in 2D plasma leads to the coupling of two degenerate elliptic equations with a smooth coefficient $\alpha $ and compact terms. The coefficient $\alpha $ changes sign. The region where $\{\alpha>0\}$ is propagative, and the region where $\{\alpha <0\}$ is non propagative and elliptic. The two models are coupled through the line $\varSigma =\{\alpha =0\}$. Generically, it is an ill-posed problem and additional information must be introduced to get a satisfactory treatment at $\varSigma $. In this work, we define the solution by relying on the limiting absorption principle ($\alpha $ is replaced by $\alpha +i0^+$) in an adapted functional setting. This setting lies on the decomposition of the solution in a regular and a singular part, which originates at $\varSigma $, and on quasi-solutions. It leads to a new well-posed mixed variational formulation with coupling. As we design explicit quasi-solutions, numerical experiments can be carried out, which illustrate the good properties of this new tool for numerical computation.
Social Capital’s Role in Humanitarian Crises
Authors: Aldrich Daniel P , Kolade Oluwaseun , McMahon Kate , Smith Robert
Published: January 2020

The growing scale and persistence of humanitarian crises constitute a critical problem for nation-states, aid organizations and crisis-affected people. Many humanitarian responders continue to focus on material aid, providing essential supplies and services during these crises, while other actors restore physical infrastructures. We believe aid efforts are overlooking the pivotal nature of horizontal and vertical ties within and between communities. Using qualitative and quantitative data from Uganda and Nigeria, we show how social capital matters even during the most severe crises. Our interviews and regression analyses of survey data show that deeper reservoirs of bridging social capital associate significantly with the preparedness of individuals displaced by violence in Nigeria, and that bonding and linking social capital correlates with greater resilience for people stressed by food insecurity in Uganda’s Karamoja region. Some concrete policy recommendations emerge for aid agencies and decision-makers that can invest in rebuilding social infrastructure in affected populations.
First-order justification logic with constant domain semantics
Authors: Fitting Melvin , Salvatore Felipe
Published: January 2020

Justification logic is a term used to identify a relatively new family of modal-like logics. There is an established literature about propositional justification logic, but incursions on the first-order case are scarce. In this paper we present a constant domain semantics for the first-order logic of proofs with the Barcan Formula (FOLPb); then we prove Soundness and Completeness Theorems. A monotonic semantics for a version of this logic without the Barcan Formula is already in the literature, but constant domains require substantial new machinery, which may prove useful in other contexts as well. Although we work mainly with one system, we also indicate how to generalize these results for the quantified version of JT45, the justification counterpart of the modal logic S5. We believe our methods are more generally applicable, but initially examining specific cases should make the work easier to follow.
Ravel’s ‘Trois Poèmes de Stéphane Mallarmé’: A Philosophy of Composition
Authors: Kilpatrick Emily
Published: January 2020

In a 1927 interview Maurice Ravel declared that Stéphane Mallarmé was ‘not merely the greatest French poet, but the only French poet, since he made the French language, not designed for poetry, poetical’. Around the same period, he twice asserted that in his Trois poèmes de Stéphane Mallarmé (1913) he had sought to ‘transpose’ Mallarmé’s poetry into music. A crucial element of Mallarmé’s allusive poetry is the way it meshes content and form: his chosen forms do not merely contain the sentiment, but make it manifest. How much more complicated is the task of a composer seeking to ‘transpose’ a work from one medium to another, when form and expression are so inextricably intertwined? The present study considers how Ravel’s Mallarmé Poèmes sought to ‘transpose’ imagery and structure, and how tellingly these elements interact with Mallarmé’s reflexive poetic technique. It offers a detailed history and context for his chosen poems, suggesting a rationale for his choices, and outlining the aesthetic ideas that link them as a triptych. Exploring aspects of the songs’ harmonic and proportional design, as well as the symbolic properties of tonality, pitch, and timbre, the study argues that Ravel’s Mallarmé Poèmes realize long-held preoccupations with the nature of form and the compositional process.
Brian Ferneyhough’s ‘Transit’, The London Sinfonietta, and the Emergence of Complexity in 1977
Authors: Hawkins Roddy
Published: January 2020

In November 1977 the London Sinfonietta began its tenth-anniversary season with a performance in London of Transit by Brian Ferneyhough. The concert marks a significant moment in the formation of Ferneyhough’s public persona, just as the tenth-anniversary season marked a turning point for the London Sinfonietta. In this article I undertake a microhistory of this performance in order to ascertain how Ferneyhough’s reputation for complexity was forged in Britain. Rooted in performance and reception history, and based around close readings of key tropes, I show that early critical opinion ranged from sympathetic to ambivalent or curious; yet it never developed into the type of hostility commonly referenced in critiques of New Complexity. The historical detail of this pivotal performance, I argue, suggests the need for a broader cultural history attuned to the transitional state that characterizes both the history and the historiography of new music in the late 1970s.
Not so fast: LB-1 is unlikely to contain a 70 M⊙ black hole
Authors: El-Badry Kareem , Quataert Eliot
Published: January 2020

The recently discovered binary LB-1 has been reported to contain a ${\sim }70\, \mathrm{M}_{\odot}$ black hole (BH). The evidence for the unprecedentedly high mass of the unseen companion comes from reported radial velocity (RV) variability of the H α emission line, which has been proposed to originate from an accretion disc around a BH. We show that there is in fact no evidence for RV variability of the H α emission line, and that its apparent shifts instead originate from shifts in the luminous star’s H α absorption line. If not accounted for, such shifts will cause a stationary emission line to appear to shift in antiphase with the luminous star. We show that once the template spectrum of a B star is subtracted from the observed Keck/HIRES spectra of LB-1, evidence for RV variability vanishes. Indeed, the data rule out periodic variability of the line with velocity semi-amplitude $K_{\rm H\,\alpha } \gt 1.3\, {\rm {km}} \, s^{-1}$. This strongly suggests that the observed H α emission does not originate primarily from an accretion disc around a BH, and thus that the mass ratio cannot be constrained from the relative velocity amplitudes of the emission and absorption lines. The nature of the unseen companion remains uncertain, but a ‘normal’ stellar-mass BH with mass 5 ≲ M/M⊙ ≲ 20 seems most plausible. The H α emission likely originates primarily from circumbinary material, not from either component of the binary.
Aesthetic Emotions Reconsidered
Authors: Fingerhut Joerg , Prinz Jesse J
Published: January 2020

We define aesthetic emotions as emotions that underlie the evaluative assessment of artworks. They are separated from the wider class of art-elicited emotions. Aesthetic emotions historically have been characterized as calm, as lacking specific patterns of embodiment, and as being a sui generis kind of pleasure. We reject those views and argue that there is a plurality of aesthetic emotions contributing to praise. After presenting a general account of the nature of emotions, we analyze twelve positive aesthetic emotions in four different categories: emotions of pleasure, contemplation, amazement, and respect. The emotions that we identify in each category, including feelings of fluency, intrigue, wonder, and adoration, have been widely neglected both within aesthetics and in emotion research more broadly.
Examining the Effectiveness of Current Information Laws and Implementation Practices for Accountability of Outsourced Public Services
Authors: Waugh Megan I , Hodkinson Stuart N
Published: January 2020

Recent events linked to outsourcing such as the Grenfell Tower disaster in June 2017 and the collapse of Carillion in 2018 have again highlighted the challenges of maintaining democratic accountability of government expenditure where public services are contracted out to private companies. Although not the only focus of policy debate, pressure is building from both parliamentarians and the Information Regulator to extend UK information laws to the rapidly expanding number of private companies holding major public sector contracts. However, there remains a lack of evidence as to the nature and extent of this accountability gap and the implications for legislative reform. This article presents findings on non-compliance from a comprehensive field experiment using Freedom of Information requests on the Private Finance Initiative model of outsourcing. We demonstrate the limits of Freedom of Information as a tool for accountability and argue both legislative and regulatory reform are needed to enable proper public scrutiny of outsourced public services.
Targeting bioenergetics prevents CD4 T cell–mediated activation of synovial fibroblasts in rheumatoid arthritis
Authors: Petrasca Andreea , Phelan James J , Ansboro Sharon , Veale Douglas J , Fearon Ursula , Fletcher Jean M
Published: January 2020

Objectives

We investigated the reciprocal relationship linking fibroblast-like synoviocytes (FLS) and T lymphocytes in the inflamed RA synovium and subsequently targeted cellular metabolic pathways in FLS to identify key molecular players in joint inflammation.

Methods

RA FLS were cultured with CD4 T cells or T cell conditioned medium (CD4CM); proliferation, expression of adhesion molecules and intracellular cytokines were examined by flow cytometry. FLS invasiveness and secreted cytokines were measured by transwell matrigel invasion chambers and ELISA, while metabolic profiles were determined by extracellular Seahorse flux analysis. Gene expression was quantified by real-time quantitative RT-PCR.

Results

Our results showed mutual activation between CD4 T cells and FLS, which resulted in increased proliferation and expression of intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 by both CD4 T cells and FLS. Furthermore, interaction between CD4 T cells and FLS resulted in an increased frequency of TNF-α+, IFN-γ+ and IL-17A+ CD4 T cells and augmented TNF-α, IFN-γ, IL-17A, IL-6, IL-8 and VEGF secretion. Moreover, CD4CM promoted invasiveness and boosted glycolysis in FLS while downregulating oxidative phosphorylation, effects paralleled by increased glucose transporters GLUT1 and GLUT3; key glycolytic enzymes GSK3A, HK2, LDHA and PFKFB3; angiogenic factor VEGF and MMP-3 and MMP-9. Importantly, these effects were reversed by the glycolytic inhibitor 2-DG and AMP analogue 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR).

Conclusion

This study demonstrates that CD4 T cells elicit an aggressive phenotype in FLS, which subsequently upregulate glycolysis to meet the increased metabolic demand. Accordingly, 2-DG and AICAR prevent this activation, suggesting that glycolytic manipulation could have clinical implications for RA treatment.
Elevating Resident Voices in Health Systems Change: Lessons From the Closure of Hahnemann University Hospital
Authors: Nasca Thomas J. , Johnson Paul Foster , Weiss Kevin B. , Brigham Timothy P.
Published: January 2020

The closure of Philadelphia’s Hahnemann University Hospital (HUH) in summer 2019 brought an abrupt end to its status as a sponsor of graduate medical education (GME). The Accreditation Council for Graduate Medical Education (ACGME) provided assistance to ensure that more than 550 residents and fellows in HUH’s 35 ACGME-accredited programs were able to transfer to new programs in which they could continue their education. As the ACGME joined other organizations in responding to HUH’s closure, it was apparent that the voices of residents and fellows should be emphasized in regulatory processes and policies that address substantial disruptions to GME and affect their education, their daily lives, and their professional futures.
Phase Ib/II trial testing combined radiofrequency ablation and ipilimumab in uveal melanoma (SECIRA-UM)
Authors: Rozeman Elisa A. , Prevoo Warner , Meier Mark A.J. , Sikorska Karolina , Van Trieu M. , van de Wiel Bart A. , van der Wal Jacqueline E. , Mallo Henk A. , Grijpink-Ongering Lindsay G. , Broeks Annegien , Lalezari Ferry , Reeves Jason , Warren Sarah , van Thienen Johannes V. , van Tinteren Harm , Haanen John B.A.G. , Kapiteijn Ellen , Blank Christian U.
Published: January 2020

Approximately, 50% of patients with uveal melanoma develop distant metastasis for which no standard therapy is established. In contrast to cutaneous melanoma, the anti-CTLA-4 antibody ipilimumab showed no clinical activity in uveal melanoma. Liver directed therapies improve local control, but fail to show overall survival (OS) benefit. Preclinical experiments demonstrated that radiofrequency ablation (RFA) induced durable responses in combination with anti-CTLA-4. The aim of this phase Ib/II study was to assess safety and efficacy of RFA plus ipilimumab in uveal melanoma. Patients underwent RFA of one liver lesion and subsequently received four courses ipilimumab 0.3, 3 or 10 mg/kg every 3 weeks in a 3 + 3 design. Primary endpoints were safety in terms of dose limiting toxicities per cohort to define the recommended phase II dose (RP2D) in the phase Ib part and confirmed the objective response rate and disease control rate (DCR) of non-RFA lesions in the phase II part. Secondary endpoints were progression-free survival (PFS) and OS. Ipilimumab 10 mg/kg + RFA was initially defined as the RP2D. However, after 19 patients, the study was amended to adjust the RP2D to ipilimumab 3 mg/kg + RFA, because 47% of patients treated with 10 mg/kg had developed grade 3 colitis. In the 3 mg/kg cohort, also 19 patients have been treated. Immunotherapy-related grade ≥3 adverse events were observed in 53% of patients in the 10 mg/kg cohort versus 32% in the 3 mg/kg cohort. No confirmed objective responses were observed; the confirmed DCR was 5% in the 10 mg/kg cohort and 11% in the 3 mg/kg cohort. Median PFS was 3 months and comparable for both cohorts, median OS was 14.2 months for the 10 mg/kg cohort versus 9.7 months for the 3 mg/kg cohort. Combining RFA with ipilimumab 3 mg/kg was well tolerated, but showed very limited clinical activity in uveal melanoma.
Fibrinolytic shutdown diagnosed with rotational thromboelastometry represents a moderate form of coagulopathy associated with transfusion requirement and mortality
Authors: David Jean-Stephane , Lambert Aline , Bouzat Pierre , Incagnoli Pascal , Geay-Baillat Anne-Marie , Taverna Xavier-Jean , Inaba Kenji , Maegele Marc
Published: January 2020

BACKGROUND

Viscoelastic techniques have made it possible to describe specific fibrinolytic phenotypes (physiological, hyperfibrinolysis and shutdown) and to establish a relationship of these phenotypes with outcome. However, there remains a debate as to whether shutdown is a state of hypercoagulability or rather a coagulopathy with moderate fibrinolysis and fibrinogen consumption.

OBJECTIVES

Our objectives were to describe the relationship between fibrinolytic phenotypes and outcomes, and to report the effects of tranexamic acid (TXA) administration.

DESIGN

This was a retrospective analysis of prospectively acquired data from a trauma registry.

SETTING

An academic level 1 trauma centre in the Lyon Region, from March 2011 to December 2016.

PATIENTS

We included all injured patients who had a rotational thromboelastometry analysis at admission. Fibrinolytic phenotypes were determined according to the maximum lysis: shutdown less than 3%, physiological 3 to 15%, hyperfibrinolysis more than 15%.

MAIN OUTCOME MEASURE

Mortality at 24 h and at hospital discharge.

RESULTS

During the study period, 473 patients were included with the following phenotypes: physiological (344 patients, 73%), shutdown (107 patients, 23%) and hyperfibrinolysis (22 patients, 5%). There was an increase in injury severity, prothrombin time ratio, fibrin degradation products and transfusion requirements from the physiological to the shutdown and hyperfibrinolysis phenotypes. Prehospital TXA administration increased the rate of shutdown and decreased the maximum lysis value at admission. After adjustment, multivariate analysis showed that fibrinolytic phenotypes, but not TXA, were independently associated with an increased risk of early death and death before hospital discharge: shutdown [odds ratio (95% confidence interval)] 2.4 (1.2 to 4.8) and hyperfibrinolysis 67.9 (7.4 to 624.2).

CONCLUSION

The results of the current study suggest that shutdown, which is associated with injury severity and mortality, probably reflects a moderate form of coagulopathy and fibrinolysis rather than a hypercoagulopathy. Therefore, the observation of shutdown fibrinolysis on thromboelastography/rotational thromboelastometry should not lead to withholding but rather to the administration of TXA.
Adult Primary Capillary Hemangioma of the Sclera: A Previously Undescribed Entity With a Review of Epibulbar Vascular Lesions
Authors: Jakobiec Frederick A. , Hanbazazh Mehenaz , Cortes Barrantes Paula , Chodosh James
Published: January 2020

Purpose:

The objective of this article is to document a unique case of a primary hemangioma and review epibulbar vascular tumors of the conjunctiva and episclera.

Methods:

A case report with detailed histopathologic, histochemical, and immunohistochemical studies coupled with a comprehensive review of the relevant literature with a tabulation of previously reported epibulbar vascular lesions was performed.

Results:

A vascular tumor developed in a 46-year-old woman over 2–3 months that histopathologically was located in the superficial third of the normally avascular sclera and was composed of capillary caliber vessels. CD31 and CD34 positivity established the vascular nature of the lesion. Despite its adult onset, the tumor was also glut-1 positive, a vascular characteristic of childhood capillary hemangiomas that will ultimately involute. Smooth muscle actin was positive in the endothelial cells and associated pericytes. An ectatic muscular vessel identified in the midst of the lesion was interpreted as an anomalous intrascleral branch of an epibulbar anterior ciliary artery, where it perforated the sclera in the vicinity of the insertion of an extraocular rectus muscle. It was deduced to be the source of the capillary proliferation. A literature review failed to identify any previously reported epibulbar vascular tumor that originated primarily in the sclera or secondarily infiltrated this ocular tunic.

Conclusion:

An adult primary capillary intrascleral neoplasm is described as the rarest of all epibulbar vascular tumors and in keeping with the exceptional status of the ocular endothelium was glut-1 positive. This lesion must be distinguished from an array of other common and esoteric epibulbar vascular conditions.
Vaginal delivery combined with vaginal tightening surgery and perineal body repair
Authors: Wu Hui , Wang Shuang , Li Qiang , Zhou Chuande , Chen Jing
Published: January 2020

The present study aimed to investigate the feasibility of vaginal delivery combined with vaginal tightening surgery and perineal body repair.

From January 2017 to April 2017, 5 cases underwent vaginal delivery combined with vaginal tightening surgery and perineal body repair. We retrospectively analyzed the clinical data.

The incisions of 5 cases were all primary healing; vulva form was improved, and there were no postoperative hematoma, infection or vaginal mucosa prolapse. Sexual function was improved to different degrees. The pelvic muscle force test showed that both the type I and type II myofiber scores were increased.

It is feasible to perform vaginal delivery combined with vaginal tightening surgery and perineal body repair, which is a safe and effective method for improving sex life and pelvic floor function.
Efficacy and safety of percutaneous endoscopic decompression via transforaminal and interlaminar approaches for lumbar spine stenosis
Authors: Li Yuan Zhen , Zhang Hong Wei , Zhang Xiao Gang , Zhang Hui , Pan Li , Zhao Xi Yun , Ning Xue Qian , Wang Zhi Peng
Published: January 2020

Background:

Lumbar spinal stenosis (LSS) is a common and frequently-occurring disease in the elderly. Percutaneous endoscopic decompression (PED) has become the first choice for the treatment of LSS because of its small wound, mild pain and rapid recovery. The surgical approaches are mainly divided into percutaneous interlaminar approach and transforaminal approach. However, these two surgical approaches have their own advantages, disadvantages and indications. Hence, the present study aims to synthesize the available direct and indirect evidence of transforaminal approach and interlaminar approach to prove their respective advantages and disadvantages.

Methods:

The following databases will be searched: Cochrane Library, PubMed, Web of Science, Embase, CNKI, Wanfang data, and China Biomedical Literature Database (CBM). The search dates will be set from the inception to November 2019. Two researchers independently screened the literature, extracted the data and assessed the risk of bias in the included studies. The efficacy outcomes including: Back and Leg Visual Analog Scale (VAS) score, the MacNab criteria, the Oswestry Disability Index (ODI) and Japanese Orthopedic Association (JOA) score. The safety outcomes including: incidence of complications (dura tear, incomplete decompression, reoperation, etc.). The meta-analysis will be conducted using Stata 12.0 software. Grading of Recommendations Assessment, Development and Evaluation (GRADE) will be used to assess evidence quality.

Results:

The results of this meta-analysis will be published in a peer-reviewed journal.

Conclusion:

The meta-analysis will provide a comprehensive summary of the evidence for 2 approaches to PED in patients with LSS.

Protocol registration number:

CRD42019128080.
Comparison of effectiveness and safety between epidural anesthesia vs local anesthesia for percutaneous transforaminal endoscopic discectomy
Authors: Sun Jian , Fang Chao , Gao Fei , Wei Laifu , Qian Jun
Published: January 2020

Objectives:

To compare the effectiveness and safety of epidural anesthesia (EA) with those of local anesthesia (LA) for percutaneous transforaminal endoscopic discectomy (PTED) and provide reference data for clinical decision-making.

Methods:

We searched PubMed, Embase, the Cochrane library, Web of Science, Medline, ScienceDirect, and the China National Knowledge Infrastructure from inception to June 2019 in order to identify randomized and nonrandomized controlled trials comparing EA and LA for PTED. Studies assessing at least 2 of the following indicators were eligible: surgical duration, X-ray exposure time, satisfaction rate, visual analog scale (VAS) scores for pain, Oswestry Disability Index (ODI), and complications. Two assessors evaluated the quality of the literature using the Cochrane Handbook or Newcastle–Ottawa Scale. Meta-analysis was conducted using Review Manager 5.3.3 software.

Results:

Four randomized controlled trials and 4 retrospective cohort studies involving a total of 1000 patients were included. The LA and EA groups included 473 and 527 patients, respectively. Meta-analysis revealed significant intergroup differences in the intraoperative (P < .00001) and postoperative (P < .00001) lumbar VAS scores, intraoperative (P < .00001) and postoperative (P = .001) leg VAS scores, and anesthesia satisfaction rate (P < .00001), with EA being superior to LA in all aspects. There were no significant intergroup differences in the surgical duration, X-ray exposure time, postoperative ODI, and complication rate.

Conclusion:

EA is as safe as LA and produces better anesthetic effects than does LA in patients undergoing PTED. Therefore, it should be promoted as a reliable anesthetic technique for PTED.
S-1 plus apatinib as first-line palliative treatment for stage IVB gastroesophageal junction adenocarcinoma
Authors: Zhang Chu , Yu Guang-Mao , Zhang Miao , Liu Dong
Published: January 2020

Rationale:

Apatinib has been proven to significantly prolong the survival of the patients with advanced chemotherapy-refractory gastric cancer. To date, studies on apatinib plus S-1 as first-line palliative therapy for metastatic gastroesophageal junction (GEJ) cancer are rare.

Patient concerns:

A 61-year-old female patient was admitted with dysphagia, significant loss of body weight, and poor performance status.

Diagnoses:

Endoscopic biopsy revealed the diagnosis of poorly-differentiated GEJ adenocarcinoma, and the patient was clinically staged as T3NxM1G3 (IVB).

Interventions:

She had received 4 cycles of palliative therapy using oral apatinib (425 mg daily) plus S-1 (40 mg twice daily for 4 weeks, with a 2-week drug-free interval), followed by maintenance low-dose apatinib (250 mg daily) plus S-1 at the same dosage thereafter.

Outcomes:

Her progression-free survival was nearly 5 months, and the overall survival was >11 months up to now. The adverse events were tolerable.

Lessons:

Apatinib plus S-1 might be an alternative option for late-stage GEJ cancer. However, high-quality trials are warranted before the recommendation of this therapeutic regimen.
Oxycodone suppresses the lipopolysaccharide-induced neuroinflammation by downregulating nuclear factor-κB in hippocampal astrocytes of Sprague–Dawley rats
Authors: Zhou Lingxue , Fan Long , Kong Cuicui , Miao Fangfang , Wu Yan , Wang Tianlong
Published: January 2020

Neuroinflammation is a common pathogenic mechanism in several neurodegenerative diseases, and glial cells are the primary inflammatory mediators of the central nervous system (CNS). Acute neuronal injury, infection, and chronic neurodegeneration may induce astrocyte activation, which is a response characterized by hyperproliferation and release of multiple inflammatory signaling factors. The opioid analgesic oxycodone has demonstrated anti-inflammatory efficacy in peripheral tissue, but its effects on the CNS have not been studied. We evaluated the inhibitory effects of oxycodone on astrocyte activation and proinflammatory mediator production in response to lipopolysaccharide (LPS). Our results showed that oxycodone (5–20 μg/ml) dose-dependently inhibited the LPS-induced astrocytosis, as measured by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide and bromodeoxyuridine assays, as well as the overexpression of glial fibrillary acidic protein, which are two hallmarks of reactive astrogliosis in neurodegenerative diseases. Oxycodone also decreased both the mRNA and protein expression levels of proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β. Besides, oxycodone increased the expression of the nuclear factor kappa-B (NF-κB) endogenous inhibitor IκB-α, and blocked NF-κB translocation to the nucleus. The anti-inflammatory efficacy of oxycodone on rat astrocytes increased with pretreatment duration. These results suggest that oxycodone can suppress neuroinflammation by inhibiting NF-κB signaling in astrocytes. Targeting the astrocytic NF-κB-mediated inflammatory response may be an effective therapeutic strategy against diseases involving neuroinflammatory damage.
Sequence and annotation of 42 cannabis genomes reveals extensive copy number variation in cannabinoid synthesis and pathogen resistance genes
Authors: McKernan Kevin J. , Helbert Yvonne , Kane Liam T. , Ebling Heather , Zhang Lei , Liu Biao , Eaton Zachary , McLaughlin Stephen , Kingan Sarah , Baybayan Primo , Concepcion Gregory , Jordan Mark , Riva Alberto , Barbazuk William , Harkins Timothy
Published: January 2020

Cannabis is a diverse and polymorphic species. To better understand cannabinoid synthesis inheritance and its impact on pathogen resistance, we shotgun sequenced and assembled aCannabistrio (sibling pair and their offspring) utilizing long read single molecule sequencing. This resulted in the most contiguousCannabis sativaassemblies to date. These reference assemblies were further annotated with full-length male and female mRNA sequencing (Iso-Seq) to help inform isoform complexity, gene model predictions and identification of the Y chromosome. To further annotate the genetic diversity in the species, 40 male, female, and monoecious cannabis and hemp varietals were evaluated for copy number variation (CNV) and RNA expression. This identified multiple CNVs governing cannabinoid expression and 82 genes associated with resistance toGolovinomyces chicoracearum, the causal agent of powdery mildew in cannabis. Results indicated that breeding for plants with low tetrahydrocannabinolic acid (THCA) concentrations may result in deletion of pathogen resistance genes. Low THCA cultivars also have a polymorphism every 51 bases while dispensary grade high THCA cannabis exhibited a variant every 73 bases. A refined genetic map of the variation in cannabis can guide more stable and directed breeding efforts for desired chemotypes and pathogen-resistant cultivars.

Sequence and annotation of 42 cannabis genomes reveals extensive copy number variation in cannabinoid synthesis and pathogen resistance genes
4-Chloro-2-[1-(4-ethylphenyl)-4,5-diphenyl-1H-imidazol-2-yl]phenol
Authors: Shraddha K. N. , Devika S. , Begum Noor Shahina
Published: January 2020

In the title compound, C29H23ClN2O, the 5-chlorophenol ring and the imidazole ring are nearly coplanar, with a dihedral angle of 15.76 (9)° between them. The ethylphenyl ring and the two phenyl rings subtend angles of 71.09 (7), 43.95 (5) and 36.53 (9)°, respectively, with the imidazole plane. An intramolecular O—H...N hydrogen bond supports the molecular conformation, and an intermolecular C—H...O interaction, originating from an ortho-phenyl H atom, stabilizes the packing arrangement. In addition, a weak C—H...π interaction, also involving an ortho-phenyl H atom, is observed.