bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and Radiological Findings in Patients with Newly Diagnosed Graves’ Ophthalmopathy
Authors: Cevik Yakup , Taylan Sekeroglu Hande , Ozgen Burce , Erkan Turan Kadriye , Sanac Ali Sefik 
Published: May 2021

Background. Graves’ ophthalmopathy is the most common extrathyroidal manifestation of Graves’ disease. The objective of this study was to investigate the clinical ophthalmological and MRI findings in newly diagnosed Graves’ ophthalmopathy. Methods. This study included 36 newly diagnosed Graves’ disease patients and 23 control participants. Patients and control participants underwent detailed ophthalmologic examination. In addition, all subjects underwent orbital MRI examination; and sizes, cross-sectional areas, and signal intensities of extraocular muscles were also measured. Results. Based on MRI measurements, the mean exophthalmos in the left eye was significantly higher in the patient group when compared to those of controls (2.04 ± 0.29 vs. 1.85 ± 0.15 cm,

p

= 0.003). The mean long diameter of inferior oblique muscle in both the right and left eyes were significantly shorter in patients when compared to those of controls (

p

= 0.001,

p

= 0.002, resp.); however, the mean long diameter of superior oblique in the left eye was longer in patients than those of controls (

p

= 0.001). Patients had significantly higher superior oblique muscle signal intensity than those of controls in the right eye (

p

= 0.01). There was no significant difference for the other parameters between the patient and control groups. Conclusion. Our findings suggest that there is no obvious change in MRI examination despite clinical ophthalmological findings in patients with newly diagnosed Graves’ ophthalmopathy. Unnecessary MRI examination should be avoided in this patient group due to unsatisfactory cost-effectiveness.
Inhibition of CDK4/6 Promotes CD8 T-cell Memory Formation
Authors: Heckler Max , Ali Lestat R. , Clancy-Thompson Eleanor , Qiang Li , Ventre Katherine S. , Lenehan Patrick , Roehle Kevin , Luoma Adrienne , Boelaars Kelly , Peters Vera , McCreary Julia , Boschert Tamara , Wang Eric S. , Suo Shengbao , Marangoni Francesco , Mempel Thorsten R. , Long Henry W. , Wucherpfennig Kai W. , Dougan Michael , Gray Nathanael S. , Yuan Guo-Cheng , Goel Shom , Tolaney Sara M. , Dougan Stephanie K. 
Published: May 2021

Abstract

CDK4/6 inhibitors are approved to treat breast cancer and are in trials for other malignancies. We examined CDK4/6 inhibition in mouse and human CD8+ T cells during early stages of activation. Mice receiving tumor-specific CD8+ T cells treated with CDK4/6 inhibitors displayed increased T-cell persistence and immunologic memory. CDK4/6 inhibition upregulated MXD4, a negative regulator of MYC, in both mouse and human CD8+ T cells. Silencing of Mxd4 or Myc in mouse CD8+ T cells demonstrated the importance of this axis for memory formation. We used single-cell transcriptional profiling and T-cell receptor clonotype tracking to evaluate recently activated human CD8+ T cells in patients with breast cancer before and during treatment with either palbociclib or abemaciclib. CDK4/6 inhibitor therapy in humans increases the frequency of CD8+ memory precursors and downregulates their expression of MYC target genes, suggesting that CDK4/6 inhibitors in patients with cancer may augment long-term protective immunity.

Significance:
CDK4/6 inhibition skews newly activated CD8+ T cells toward a memory phenotype in mice and humans with breast cancer. CDK4/6 inhibitors may have broad utility outside breast cancer, particularly in the neoadjuvant setting to augment CD8+ T-cell priming to tumor antigens prior to dosing with checkpoint blockade.
This article is highlighted in the In This Issue feature, p. 2355
Impact of HER2 Heterogeneity on Treatment Response of Early-Stage HER2-Positive Breast Cancer: Phase II Neoadjuvant Clinical Trial of T-DM1 Combined with Pertuzumab
Authors: Filho Otto Metzger , Viale Giuseppe , Stein Shayna , Trippa Lorenzo , Yardley Denise A. , Mayer Ingrid A. , Abramson Vandana G. , Arteaga Carlos L. , Spring Laura M. , Waks Adrienne G. , Wrabel Eileen , DeMeo Michelle K. , Bardia Aditya , Dell'Orto Patrizia , Russo Leila , King Tari A. , Polyak Kornelia , Michor Franziska , Winer Eric P. , Krop Ian E. 
Published: May 2021

Abstract

Intratumor heterogeneity is postulated to cause therapeutic resistance. To prospectively assess the impact of HER2 (ERBB2) heterogeneity on response to HER2-targeted therapy, we treated 164 patients with centrally confirmed HER2-positive early-stage breast cancer with neoadjuvant trastuzumab emtansine plus pertuzumab. HER2 heterogeneity was assessed on pretreatment biopsies from two locations of each tumor. HER2 heterogeneity, defined as an area with ERBB2 amplification in &gt;5% but &lt;50% of tumor cells, or a HER2-negative area by FISH, was detected in 10% (16/157) of evaluable cases. The pathologic complete response rate was 55% in the nonheterogeneous subgroup and 0% in the heterogeneous group (P &lt; 0.0001, adjusted for hormone receptor status). Single-cell ERBB2 FISH analysis of cellular heterogeneity identified the fraction of ERBB2 nonamplified cells as a driver of therapeutic resistance. These data suggest HER2 heterogeneity is associated with resistance to HER2-targeted therapy and should be considered in efforts to optimize treatment strategies.

Significance:
HER2-targeted therapies improve cure rates in HER2-positive breast cancer, suggesting chemotherapy can be avoided in a subset of patients. We show that HER2 heterogeneity, particularly the fraction of ERBB2 nonamplified cancer cells, is a strong predictor of resistance to HER2 therapies and could potentially be used to optimize treatment selection.
See related commentary by Okines and Turner, p. 2369.
This article is highlighted in the In This Issue feature, p. 2355
Apresentação: Semiótica e vida social
Authors: Schwartzmann Matheus Nogueira , Sousa Silvia Maria de 
Published: May 2021

A semiótica brasileira, que hoje pode até mesmo ser reconhecida como uma “escola” de pensamento independente, tem sido exercida “com inteligência, sensibilidade, emoção e gosto particulares” (Schwartzmann; Portela, 2017, p. 65), não se limitando a objetos clássicos, mostrando-se sempre receptiva e aberta ao diálogo interdisciplinar com outras correntes linguísticas e com outras áreas do conhecimento. Reconhecendo justamente essa tendência na semiótica brasileira, e buscando contribuir com o avanço dessas reflexões entre semiótica e vida social, o Grupo de Trabalho de Semiótica da ANPOLL elegeu esse tema para nortear o biênio 2018-2020. No âmbito do Grupo de Trabalho, foram gestados os artigos que aqui se apresentam. Pudemos reunir cinco eixos de discussão da semiótica contemporânea, como tem sido desenvolvida no Brasil, os quais fazem avançar questões que nos são próprias, seja de um ponto de vista teórico, seja do ponto de vista dos objetos que continuam a desafiar a teoria: (1) os discursos políticos; (2) o diálogo entre semiótica e ensino; (3) a historiografia semiótica; (4) os discursos nas redes digitais e sociais; e (5) as práticas de inscrição urbana. Esses cinco eixos temáticos podem ser tomados como diferentes faces da vida social, que podem ser descritas e explicadas por meio da semiótica.
Comparative Analysis Following Implementation of Two Types of Y‐Composite Multiarterial Revascularization Strategies at a Single Academic Institution
Authors: Gharibeh Lara , Hosoyama Katsuhiro , Glineur David , Shaw Richard E. , Lapierre Harry , Ruel Marc , Grau Juan B. 
Published: May 2021

Background
We compared early outcomes, at a single academic institution, of implementing full coronary revascularization in coronary artery bypass grafting using multiarterial Y‐composite grafts with multiple sequential anastomoses.

Methods and Results

Clinical records of 425 consecutive patients who underwent coronary artery bypass grafting using Y‐grafting with left internal mammary artery and radial artery (Y‐RA group) or right internal mammary artery (Y‐RIMA group) from 2015 to 2019, were reviewed. These were compared with the institutional experience of isolated coronary artery bypass grafting cases (in situ on pump/off pump) for the same period of time. When comparing the 4 groups, the Y‐RIMA/RA groups revealed a higher number of distal anastomosis than the in situ on‐ or off‐pump groups. When the number of distal arterial anastomosis was analyzed, there was a superiority of using the Y‐configuration compared with the in situ approach. Moreover, there were no significant differences among groups for mortality and/or major adverse cardiac and cerebrovascular events in hospital or at 30‐day follow‐up. A subanalysis comparing the Y‐RIMA group with the Y‐RA group showed that complementary grafts to the Y‐construct were required to accomplish full revascularization more frequently in the Y‐RIMA group. Full‐arterial revascularization was achieved in 92.2% of the Y‐RA group and 72.0% of the Y‐RIMA group (
P
<0.001). In 82.8% of the Y‐RA group and 30.8% of the Y‐RIMA group, revascularization was completed as an anaortic procedure (
P
<0.001).

Conclusions
The 2 types of arterial Y‐composite grafting were able to be introduced in the routine practice of our institution showing comparable results to the established institutional practice. This procedure allowed for more arterial distal anastomosis to be performed safely without compromising outcomes.
Decrypting the Signs of Regulatory Competition in Regulating Cryptoassets
Authors: Chiu Iris H-Y 
Published: May 2021

Abstract
The icos market has challenged financial regulators in terms of determining fit with existing regimes and consideration for regulatory reform. Regulatory divergences have emerged in a number of jurisdictions and we discuss three dominant approaches in relation to hegemonic, self-regulatory and enabling regimes. These reflect different assumptions and regulators’ understandings of the cryptoasset industry, and we argue that the ‘terms for competition’ in relation to supply and demand side needs are still being discovered and are incomplete. This provides a unique opportunity for regulators to jettison familiar assumptions in relation to corporatized securities issuers or institutional investors in order to discover what governance needs are truly at stake. This may pose challenges for coherence with existing regulation but coherence should not itself be an obstacle for learning and potentially, reform. We also argue that signs of international regulatory coordination in relation to the Libra project are not necessarily reflective of a wider trend for the cryptoasset industry. This is because regulators can apply existing and familiar financial regulation paradigms more easily to the Libra Association, in particular its leading founding member Facebook. The cryptoasset market is still likely to give rise to diversity and should facilitate the discovery of new bases for regulatory thinking and policy, uncoordinated or otherwise.
Ensemble Oscillation Correction (EnOC): Leveraging oscillatory modes to improve forecasts of chaotic systems
Authors: Bach Eviatar , Mote Safa , Krishnamurthy V. , Sharma A. Surjalal , Ghil Michael , Kalnay Eugenia 
Published: May 2021

AbstractOscillatory modes of the climate system are among its most predictable features, especially at intraseasonal time scales. These oscillations can be predicted well with data-driven methods, often with better skill than dynamical models. However, since the oscillations only represent a portion of the total variance, a method for beneficially combining oscillation forecasts with dynamical forecasts of the full system was not previously known. We introduce Ensemble Oscillation Correction (EnOC), a general method to correct oscillatory modes in ensemble forecasts from dynamical models. We compute the ensemble mean—or the ensemble probability distribution—with only the best ensemble members, as determined by their discrepancy from a data-driven forecast of the oscillatory modes. We also present an alternate method which uses ensemble data assimilation to combine the oscillation forecasts with an ensemble of dynamical forecasts of the system (EnOCDA). The oscillatory modes are extracted with a time-series analysis method called multi-channel singular spectrum analysis (M-SSA), and forecast using an analog method. We test these two methods using chaotic toy models with significant oscillatory components, and show that they robustly reduce error compared to the uncorrected ensemble. We discuss the applications of this method to improve prediction of monsoons as well as other parts of the climate system.
Skillful Subseasonal Prediction of United States Extreme Warm Days and Standardized Precipitation Index in Boreal Summer
Authors: Miller Douglas E. , Wang Zhuo , Li Bo , Harnos Daniel S. , Ford Trent 
Published: May 2021

AbstractSkillful subseasonal prediction of extreme heat and precipitation greatly benefits multiple sectors, including water management, public health, and agriculture, in mitigating the impact of extreme events. A statistical model is developed to predict the weekly frequency of extreme warm days and 14-day standardized precipitation index (SPI) during boreal summer in the United States (US). We use a leading principal component of US soil moisture and an index based on the North Pacific sea surface temperature (SST) as predictors. The model outperforms the NCEP’s Climate Forecast System version 2 (CFSv2) at weeks 3-4 in the eastern US. It is found that the North Pacific SST anomalies persist several weeks and are associated with a persistent wave train pattern (WTZ500), which leads to increased occurrences of blocking and extreme temperature over the eastern US. Extreme dry soil moisture conditions persist into week 4 and are associated with an increase in sensible heat flux and decrease in latent heat flux, which may help maintain the overlying anticyclone. The clear sky conditions associated with blocking anticyclones further decrease soil moisture conditions and increase the frequency of extreme warm days. This skillful statistical model has the potential to aid in irrigation scheduling, crop planning, reservoir operation, and provide mitigation of impacts from extreme heat events.
Upstream extension of a bottom-advected plume and its mechanism: The case of the Yellow River
Authors: Yu Xiaojie , Guo Xinyu , Gao Huiwang , Zou Tao 
Published: May 2021

AbstractHydrographic surveys have revealed that the Yellow River plume propagates in the direction opposite to that of a Kelvin wave (upstream) under a low river discharge condition, but turns downstream as the river discharge increases. A numerical model reproduced the upstream extension of the plume under the low river discharge condition and the transition to the downstream direction under the high river discharge condition, and confirmed that the summer wind is not the necessary condition for upstream extension of the plume. With the condition of low river discharge, the model also indicated the dependence of the upstream extension of the plume on the tidal range: extending upstream in spring tide but turning downstream in neap tide. The upstream movement of the plume results from the upstream transport of freshwater that depends on the upstream tide-induced residual current around the river mouth and the downstream density-driven current around the offshore plume front. With the condition of high river discharge, the upstream tide-induced residual current cannot compete with the downstream density-driven current and the plume turns downstream. Momentum analysis confirms the important roles of advection term and viscosity term in the condition of low river discharge and the shift to a Coriolis force-dominated system under high river discharge condition. An idealized model study suggests a dimensionless number for the river discharge changing the river plume extension from upstream to downstream under a specific upstream ambient current around the river mouth.
Clinical, oculographic, and vestibular test characteristics of vestibular migraine
Authors: Young Allison S , Nham Benjamin , Bradshaw Andrew P , Calic Zeljka , Pogson Jacob M , D’Souza Mario , Halmagyi G Michael , Welgampola Miriam S 
Published: May 2021

Background We characterise the history, vestibular tests, ictal and interictal nystagmus in vestibular migraine. Method We present our observations on 101 adult-patients presenting to an outpatient facility with recurrent spontaneous and/or positional vertigo whose final diagnosis was vestibular migraine (n = 27) or probable vestibular migraine (n = 74). Ictal and interictal video-oculography, caloric and video head impulse tests, vestibular-evoked myogenic potentials and audiometry were performed. Results Common presenting symptoms were headache (81.2%), spinning vertigo (72.3%), Mal de Débarquement (58.4%), and motion sensitivity (30.7%). With fixation denied, ictal and interictal spontaneous nystagmus was observed in 71.3 and 14.9%, and purely positional nystagmus in 25.8 and 55.4%. Spontaneous ictal nystagmus was horizontal in 49.5%, and vertical in 21.8%. Ictal spontaneous and positional nystagmus velocities were 5.3 ± 9.0°/s (range 0.0–57.4), and 10.4 ± 5.8°/s (0.0–99.9). Interictal spontaneous and positional nystagmus velocities were <3°/s in 91.8 and 23.3%. Nystagmus velocities were significantly higher when ictal ( p < 0.001/confidence interval: 2.908‒6.733, p < 0.001/confidence interval: 5.308‒10.085). Normal lateral video head impulse test gains were found in 97.8% (mean gain 0.95 ± 0.12) and symmetric caloric results in 84.2% (mean canal paresis 7.0 ± 23.3%). Air- and bone-conducted cervical-vestibular-evoked myogenic potential amplitudes were symmetric in 88.4 and 93.4% (mean corrected amplitude 1.6 ± 0.7, 1.6 ± 0.8) with mean asymmetry ratios of 13.0 and 9.0%. Air- and bone-conducted ocular-vestibular-evoked myogenic potentials were symmetric in 67.7 and 97.2% (mean amplitude 9.2 ± 6.4 and 20.3 ± 12.8 µV) with mean asymmetry ratios of 15.7 and 9.9%. Audiometry was age consistent and symmetric in 85.5%. Conclusion Vestibular migraine is characterised by low velocity ictal spontaneous nystagmus, which can be horizontal, vertical, or torsional, and normal audiovestibular test results.
Prevalence and Outcomes of Multi-Drug Resistant Blood Stream Infections Among Nursing Home Residents Admitted to an Acute Care Hospital
Authors: Aliyu Sainfer , McGowan Kevin , Hussain Dilbi , Kanawati Lama , Ruiz Maria , Yohannes Seife 
Published: May 2021

Objective: The prevalence of multi-drug resistant organism (MDRO) colonization in nursing home residents has been well documented, but little is known about the impact of MDRO bloodstream infections (BSIs). The aim of this study was to assess the prevalence, cost, and outcomes of MDRO-BSI vs. non-MDRO-BSI among nursing home residents. Design: Retrospective cohort study Setting: 960 bed tertiary academic medical center Patients: Persons ≥18 years old admitted to an acute care tertiary hospital from Skilled Nursing Facilities with a diagnosis of sepsis between 2015 and 2018. Interventions: Retrospective analysis of prevalence and outcomes. Measurements and Main Results: Among patients admitted to the study hospital with a diagnosis of sepsis during the study period, 7% were from nursing homes. The prevalence of MDRO-BSI was 47%. We identified 54 (50%) gram positive BSIs, 48 (45%) gram negative BSI and 5 (5%) fungal BSI. Thirty-one (57%) of the gram-positive infections and 14 (30%) of the gram-negative infections were with MDROs. The prevalence of BSI organisms were Staphylococcus aureus in 24%, Escherichia coli in 14%, Proteus mirabilis in 13%, Staphylococcus epidermidis in 8%, Enterococcus faecalis in 7%, and Klebsiella pneumoniae in 6%. We found that intensive care unit length of stay (7 days vs 5 days, P = .009), direct cost ($13,639 vs $9,922, P = .027), and total cost ($23,752 vs $17,900 P = .032) were significantly higher in patients with MDRO-BSI vs. non-MDRO-BSI. Patients with MDRO-BSI were twice as likely to receive inappropriate empiric antiinfective therapy (31% vs 16%, P = .006) and were more likely to die (49.1% vs 29.6%, P = .049). Conclusion: Nursing home residents have a high prevalence of MDRO-BSI, which is associated with higher risk of receiving inappropriate initial anti-infective therapy, higher cost, higher ICU LOS, and higher mortality. Our research adds new information about the prevalence of fungemia in this population.
Multiaxial classification in child and adolescent mental health – a reaffirmation of benefit and practical applications
Authors: Mayall Mark , McDermott Brett , Sadhu Raja , Husodo Cortney 
Published: May 2021

Objective: Classification systems and their practical implications have become increasingly important in child and adolescent psychiatry. This paper presents the evolution and practical applications of a multiaxial classification system for children and adolescents presenting to mental health services. Included are some worked examples demonstrating both the complexity of many presentations and how broadening the use of the multiaxial system can help in identifying appropriate interventions. Conclusions: Classification systems in child and adolescent psychiatry have largely remained uniaxial in nature. A multiaxial system encapsulates the broader biopsychosocial aspects of the presenting child or adolescent, and orders complex data in a concise manner. This approach can be used to concisely communicate with other treating clinicians, and assist with case reviews, formulation and teaching.
A Systematic Review of the Use of the Implicit Relational Assessment Procedure (IRAP) to Assess Implicit Biases Held by Professionals Toward Client Populations
Authors: Sereno Michelle , Quigley Jennifer , Smith Gregory S. 
Published: May 2021

Implicit biases held by professionals, functioning outside conscious awareness, can negatively affect client outcomes and professional well-being. Purpose: This systematic review evaluated evidence in the literature of Implicit Relational Assessment Procedure (IRAP) utility for assessing implicit biases held by professionals toward client populations. Method: Included studies were those published 2000 through 2020 using IRAP to measure implicit biases in professionals toward consumers. Results: Eight studies met inclusion criteria, with two meeting borderline requirements. Results support IRAP reliability and validity for identifying implicit biases. Variation presents across studies in reporting and analysis of IRAP effects. Discussion: Convergence and divergence between implicit and explicit measures are discussed in terms of relational responding. Results are limited by the relative paucity of studies meeting inclusion criteria and by inconsistencies in data reporting and analysis. Methods for selecting IRAP stimuli are discussed, with a call for a more function-driven approach. Standardization of IRAP methodology is recommended to facilitate extension.