bluuebunny/crossref_metadata_2025_split huggingface dataset:
Calculations with graded perverse-coherent sheaves
Authors: Achar Pramod N , Hardesty William D 
Published: June 2019

Abstract
In this paper, we carry out several computations involving graded (or ${{\mathbb {G}}_{\textrm {m}}}$-equivariant) perverse-coherent sheaves on the nilpotent cone of a reductive group in good characteristic. In the first part of the paper, we compute the weight of the ${{\mathbb {G}}_{\textrm {m}}}$-action on certain normalized (or ‘canonical’) simple objects, confirming an old prediction of Ostrik. In the second part of the paper, we explicitly describe all simple perverse-coherent sheaves for $G = PGL_3$, in every characteristic other than 2 or 3. Applications include an explicit description of the cohomology of tilting modules for the corresponding quantum group, as well as a proof that $\textsf {PCoh}^{{{\mathbb {G}}_{\textrm {m}}}}({\mathcal {N}})$ never admits a positive grading when the characteristic of the field is greater than 3.
Long-term safety of sarilumab in rheumatoid arthritis: an integrated analysis with up to 7 years’ follow-up
Authors: Fleischmann Roy , Genovese Mark C , Lin Yong , St John Gregory , van der Heijde Désirée , Wang Sheldon , Gomez-Reino Juan Jose , Maldonado-Cocco Jose Antonio , Stanislav Marina , Kivitz Alan J , Burmester Gerd R 
Published: June 2019

Abstract

Objective
Sarilumab is a human monoclonal antibody that blocks IL-6 from binding to membrane-bound and soluble IL-6 receptor-α. We assessed the long-term safety of sarilumab in patients from eight clinical trials and their open-label extensions.

Methods
Data were pooled from patients with rheumatoid arthritis who received at least one dose of sarilumab in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs; combination group) or as monotherapy (monotherapy group). Treatment-emergent adverse events (AEs) and AEs and laboratory values of special interest were assessed.

Results
2887 patients received sarilumab in combination with csDMARDs and 471 patients received sarilumab monotherapy, with mean exposure of 2.8 years and 1.7 years, maximum exposure 7.3 and 3.5 years, and cumulative AE observation period of 8188 and 812 patient-years, respectively. Incidence rates per 100 patient-years in the combination and monotherapy groups, respectively, were 9.4 and 6.7 for serious AEs, 3.7 and 1.0 for serious infections, 0.6 and 0.5 for herpes zoster (no cases were disseminated), 0.1 and 0 for gastrointestinal perforations, 0.5 and 0.2 for major adverse cardiovascular events, and 0.7 and 0.6 for malignancy. Absolute neutrophil counts &lt;1000 cells/mm3 were recorded in 13% and 15% of patients, respectively. Neutropenia was not associated with increased risk of infection or serious infection. Analysis by 6-month interval showed no signal for increased rate of any AE over time.

Conclusion
The long-term safety profile of sarilumab, either in combination with csDMARDs or as monotherapy, remained stable and consistent with the anticipated profile of a molecule that inhibits IL6 signalling.
Biologics and anaphylaxis
Authors: Sala-Cunill Anna , Luengo Olga , Cardona Victoria 
Published: June 2019

Purpose of review
The use of biologicals as therapeutic agents in oncology and other inflammatory diseases has dramatically increased during the last years. Due to their biological nature and inherent immunological activity, they are able to induce important adverse events, such as cytokine release reactions (rapid release of proinflammatory cytokines), serum sickness disease, and immediate or delayed hypersensitivity reactions, including anaphylaxis. The aim of the current article is to review the state of the art of anaphylaxis because of biological agents.

Recent findings
Different phenotypes, and potential underlying endotypes, have been described in anaphylactic reactions to biologicals. There seems to be a spectrum from type 1 reactions (IgE or non-IgE-mediated) to cytokine release reactions, with some reactions falling in between both. Management should be directed according to such phenotypes.

Summary
There is ongoing research to further define immediate adverse reactions to biologicals and to find relevant biomarkers to aid in their diagnosis. Such information will serve in defining their immediate and long term management.
Role of the ocular surface microbiome in allergic disease
Authors: Cavuoto Kara M. , Stradiotto Allison C. , Galor Anat 
Published: June 2019

Purpose of review
The purpose of this review is to provide an update regarding new and emerging data on the role of the ocular surface microbiome in allergic disease.

Recent findings
Recent findings support the role of the microbiome in the pathophysiology of allergic disease of the ocular surface.

Summary
Understanding the role of the ocular surface microbiome in allergic disease may provide a new target for the development of therapeutic interventions.
Positioning the Work of Health Professions Education Scholarship Units: How Canadian Directors Harness Institutional Logics Within Institutional Orders to Convey Unit Legitimacy
Authors: Kahlke Renate , Varpio Lara 
Published: June 2019

Purpose
Health professions education scholarship unit (HPESU) leaders often struggle to articulate their impact within local contexts. Previous research has described what markers of success and institutional logics to consider when crafting statements of impact; there is a need to clarify how HPESU leaders convey their messages to navigate competing demands. This study examined how leaders argue the legitimacy of their HPESUs’ activities.

Method
The institutional logics perspective offered a lens for understanding how legitimacy claims are constructed through larger institutional orders. Interviews with leaders from 12 Canadian HPESUs discussed their unit’s work, the stakeholders that leaders sought to satisfy, and how they defined success. Data were generated in 2011–2012 and analyzed anew in 2017–2018. The authors inductively analyzed the data, using institutional logics and institutional orders as sensitizing concepts to identify the linguistic constructions harnessed by participants.

Results
HPESU leaders engaged with 2 dominant logics: research and service. These aligned with institutional orders: the profession and community, respectively. While a few HPESU leaders deployed only one logic throughout the course of an interview, many engaged with more than one, compartmentalizing logics specific to different audiences and activities or blending logics to create novel ways of framing their work.

Conclusions
The institutional logics available in a context vary. What constitutes a compelling legitimacy claim is different from one institutional context to the next. The authors identify strategies that leaders used to position their HPESU for success and discuss the basis on which these claims are made.
Competencies and Feedback on Internal Medicine Residents’ End-of-Rotation Assessments Over Time: Qualitative and Quantitative Analyses
Authors: Tekian Ara , Park Yoon Soo , Tilton Sarette , Prunty Patrick F. , Abasolo Eric , Zar Fred , Cook David A. 
Published: June 2019

Purpose
To examine how qualitative narrative comments and quantitative ratings from end-of-rotation assessments change for a cohort of residents from entry to graduation, and explore associations between comments and ratings.

Method
The authors obtained end-of-rotation quantitative ratings and narrative comments for 1 cohort of internal medicine residents at the University of Illinois at Chicago College of Medicine from July 2013–June 2016. They inductively identified themes in comments, coded orientation (praising/critical) and relevance (specificity and actionability) of feedback, examined associations between codes and ratings, and evaluated changes in themes and ratings across years.

Results
Data comprised 1,869 assessments (828 comments) on 33 residents. Five themes aligned with ACGME competencies (interpersonal and communication skills, professionalism, medical knowledge, patient care, and systems-based practice), and 3 did not (personal attributes, summative judgment, and comparison to training level). Work ethic was the most frequent subtheme. Comments emphasized medical knowledge more in year 1 and focused more on autonomy, leadership, and teaching in later years. Most comments (714/828 [86%]) contained high praise, and 412/828 (50%) were very relevant. Average ratings correlated positively with orientation (β = 0.46, P < .001) and negatively with relevance (β = −0.09, P = .01). Ratings increased significantly with each training year (year 1, mean [standard deviation]: 5.31 [0.59]; year 2: 5.58 [0.47]; year 3: 5.86 [0.43]; P < .001).

Conclusions
Narrative comments address resident attributes beyond the ACGME competencies and change as residents progress. Lower quantitative ratings are associated with more specific and actionable feedback.
Multi-Compartment Profiling of Bacterial and Host Metabolites Identifies Intestinal Dysbiosis and Its Functional Consequences in the Critically Ill Child
Authors: Wijeyesekera Anisha , Wagner Josef , De Goffau Marcus , Thurston Sarah , Rodrigues Sabino Adilson , Zaher Sara , White Deborah , Ridout Jenna , Peters Mark J. , Ramnarayan Padmanabhan , Branco Ricardo G. , Torok M. Estee , Valla Frederic , Meyer Rosan , Klein Nigel , Frost Gary , Parkhill Julian , Holmes Elaine , Pathan Nazima 
Published: June 2019

Objectives:
Adverse physiology and antibiotic exposure devastate the intestinal microbiome in critical illness. Time and cost implications limit the immediate clinical potential of microbial sequencing to identify or treat intestinal dysbiosis. Here, we examined whether metabolic profiling is a feasible method of monitoring intestinal dysbiosis in critically ill children.

Design:
Prospective multicenter cohort study.

Setting:
Three U.K.-based PICUs.

Patients:
Mechanically ventilated critically ill (n = 60) and age-matched healthy children (n = 55).

Interventions:
Collection of urine and fecal samples in children admitted to the PICU. A single fecal and urine sample was collected in healthy controls.

Measurements and Main Results:
Untargeted and targeted metabolic profiling using 1H-nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry or urine and fecal samples. This was integrated with analysis of fecal bacterial 16S ribosomal RNA profiles and clinical disease severity indicators. We observed separation of global urinary and fecal metabolic profiles in critically ill compared with healthy children. Urinary excretion of mammalian-microbial co-metabolites hippurate, 4-cresol sulphate, and formate were reduced in critical illness compared with healthy children. Reduced fecal excretion of short-chain fatty acids (including butyrate, propionate, and acetate) were observed in the patient cohort, demonstrating that these metabolites also distinguished between critical illness and health. Dysregulation of intestinal bile metabolism was evidenced by increased primary and reduced secondary fecal bile acid excretion. Fecal butyrate correlated with days free of intensive care at 30 days (r = 0.38; p = 0.03), while urinary formate correlated inversely with vasopressor requirement (r = –0.2; p = 0.037).

Conclusions:
Disruption to the functional activity of the intestinal microbiome may result in worsening organ failure in the critically ill child. Profiling of bacterial metabolites in fecal and urine samples may support identification and treatment of intestinal dysbiosis in critical illness.
Reversible Impaired Methotrexate Clearance After Platinum-Based Chemotherapy for Osteosarcoma
Authors: Oude Munnink Thijs , van der Meer Alex , de Haan Jacco , Touw Daan , van Kruchten Michel 
Published: June 2019

Abstract:
The authors present a case of an 18-year-old man with metastasized osteosarcoma, admitted for methotrexate (MTX) treatment combined with cisplatin and doxorubicin. During the first cycle, severe MTX toxicity was observed with increased MTX serum levels and delayed MTX clearance requiring rescue treatment with intensified leucovorin. In the following cycles, cisplatin and doxorubicin were discontinued, and MTX dose was reduced. The elimination half-life slowly improved over the following cycles suggesting a reversible cause responsible for reduced MTX clearance and toxicity during the first cycle. Cisplatin is well-known for its nephrotoxic effects and can induce reversible tubular injury. Previous treatment with cisplatin may well have been responsible for decreased MTX clearance, and combination treatment should be used with adequate monitoring of MTX levels. Other factors that may have contributed, such as urine alkalization, gene polymorphisms, and other drug–drug interactions are discussed.
Early versus late recurrence of centrally located hepatocellular carcinoma after mesohepatectomy
Authors: Zhao Jun , Li Wei , Mao Jie 
Published: June 2019

Abstract
The aim of this study was to investigate the features, treatment, and prognosis of early versus late recurrence of centrally located hepatocellular carcinoma (CL-HCC) after mesohepatectomy (MH).
Three hundred forty eight patients with CL-HCC undergoing MH were included. Data on clinicopathological characteristics, initial surgical details, timing and sites of tumor recurrence, management after recurrence, and long-term outcomes were analyzed.
The optimal cutoff value to differentiate early (71 patients, 64.5%) versus late (39, 35.5%) recurrence was defined as 12 months. Patients with early recurrence (ER) had higher alpha fetoprotein (AFP) level (P < .001), more advanced tumor stage (P = .024), and higher incidence of microvascular invasion (MVI, P = .001). Patients with ER had higher incidence of local tumor recurrence (P = .027) and higher average number of recurrent nodules (P = .016) than patients with LR. Patients after ER showed a better overall survival (from date of diagnosis of recurrence) than after late recurrence (LR). Patients with ER had less chances of curative treatment (14.1% vs 41.0%, P = .004) after tumor recurrence than patients with LR. Multivariable analyses revealed that liver cirrhosis (P < .001) and tumor differentiation (P < .001) were associated with an increased likelihood of LR, while multiple tumor number (P = .005), type IV classification (P = .012), and MVI (P < .001) were independent risk factors related to ER.
ER and LR after MH for CL-HCC were associated with different risk predictors and prognosis. Data on the timing of recurrence may inform decisions about postoperative adjuvant treatment, as well as help to predict long-term survival for these patients.
Predictive role of subcomponents of the left arcuate fasciculus in prognosis of aphasia after stroke
Authors: Yu Qiwei , Wang Hong , Li Shuqing , Dai Yanhong 
Published: June 2019

Abstract
The relationship between the left arcuate fasciculus (AF) and stroke-related aphasia is unclear. In this retrospective study, we aimed to investigate the role of subcomponents of the left AF in predicting prognosis of aphasia after stroke. Twenty stroke patients with aphasia were recruited and received language assessment as well as diffusion tensor tractography scanning at admission. According to injury of the left AF, the participants were classified into four groups: group A (4 cases), the AF preserved intactly; group B (6 cases), the anterior segment injured; group C (4 cases), the posterior segment injured; and group D (6 cases), completely injured. After a consecutive speech therapy, language assessment was performed again. Changes of language functions among the groups were compared and the relation between these changes with segments injury of the AF was analyzed. After therapy, relatively high increase score percentage changes in terms of all the subcategories of language assessment were observed both in group A and C; by contrast, only naming in group B, and spontaneous speech in group D. Although no statistical difference was demonstrated among the four groups. In addition, there was no significant correlation between improvement of language function with segments injury of the AF. The predictive role of subcomponents of the left AF in prognosis of aphasia is obscure in our study. Nevertheless, it indicates the importance of integrity of the left AF for recovery of aphasia, namely that preservation of the left AF on diffusion tensor tractography could mean recovery potential of aphasia after stroke.
The cumulative venous thromboembolism incidence and risk factors in intensive care patients receiving the guideline-recommended thromboprophylaxis
Authors: Zhang Chuanlin , Zhang Zeju , Mi Jie , Wang Xueqin , Zou Yujun , Chen Xiaoya , Nie Zhi , Luo Xinyi , Gan Ruiying 
Published: June 2019

Abstract
Few prospective studies have reported the cumulative incidence of venous thromboembolism (VTE) in the intensive care unit (ICU), especially for patients receiving guideline-recommended VTE prophylaxis. We aimed to design a prospective observational study to investigate the cumulative incidence and risk factors of ICU-acquired VTE for those populations.
We prospectively studied 281 consecutively included patients in the ICU at a single center. All patients provided informed consent. Patients received ultrasound evaluation and were followed for VTE before ICU discharge or within 28 days of ICU stay. The type of VTE thromboprophylaxis was also recorded for all patients. Variables from univariate analyses that were associated with VTE were included in the binary logistic regression analysis to determine VTE predictors. The cumulative VTE incidence with 95% confidence interval (CI) was estimated using Kaplan–Meier methods.
Patients had a median age of 60 years (range, 18–89) and an acute physiology and chronic health evaluation II score of 17 (range, 4–36). Despite all patients receiving guideline-recommended thromboprophylaxis, the cumulative incidence of VTE at 7, 14, 21, and 28 days was 4.45% (95% CI 2.55–7.71), 7.14% (95% CI 4.61–10.97), 7.53% (95% CI 4.92–11.43), and 9.55% (95% CI 6.55–13.81), respectively. Central venous catheter use (P = .002, odds ratio [OR] = 4.50), Caprini score (P = .012, OR = 1.20), and ICU length of stay (P = .006, OR = 1.08) were independent risk factors related to the incidence of VTE for patients admitted to the ICU.
Our prospective observational study found that the 28-day cumulative incidence of VTE was relatively high for patients admitted to the ICU, despite the use of guideline-recommended thromboprophylaxis. Patients with femoral central venous catheter, prolonged ICU length of stay, or a high Caprini score may have an increased risk of developing VTE.
Relationship between CXC chemokine receptor 4 expression and prognostic significance in acute myeloid leukemia
Authors: Cao Tingyong , Ye Yuanxin , Liao Hongyan , Shuai Xiao , Jin Yongmei , Su Jun , Zheng Qin 
Published: June 2019

Abstract
CXC chemokine receptor 4 (CXCR4) expression on acute myeloid leukemia (AML) cells correlated with stromal cell derived factor-1α (SDF-1α) and retained hematopoietic progenitors and leukemia cells within the bone marrow microenvironment. Here, we examined CXCR4 expression in 134 de novo AML and 21 controls by flow cytometry, evaluated the relationship between CXCR4 expression and clinical characteristics, and elucidated the prognostic significance of CXCR4 expression in AML prospectively. We found that the CXCR4 expression was significantly higher in AML patients than controls (P = .000). One hundred thirty four cases of de novo AML patients were divided into 2 groups according to the median of CXCR4 relative fluorescence intensity (RFI). CXCR4 high group (RFI >4.23) had markedly shorter overall survival (OS) and disease-free survival (DFS) than CXCR4 low group (RFI ≤4.23) in 106 AML patients who received chemotherapy (P = .002; .026, respectively). Furthermore, in the 87 non-M3 patients who received induction therapy, there was a significant decrease for OS but not for DFS in the CXCR4 high group (P = .047 and .178, respectively). Moreover, high levels of CXCR4 expression independently increased the risk of relapse in both all AML and non-M3 patients who achieved complete remission (CR) after chemotherapy (odds ratio = 1.090, P = .010; odds ratio = 1.068, P = .048, respectively). Collectively, our data suggest that CXCR4 overexpression was an independent prognostic factor for disease relapse and poorer OS in both all AML and non-M3 patients. CXCR4 expression levels can be determined at disease presentation by the flow rapidly and easily. As such, CXCR4 could be used as a potential therapeutic target in AML patients with poor prognosis.
Traditional Chinese medicine therapy reduces the risk of total knee replacement in patients with knee osteoarthritis
Authors: Lo Pei-Chia , Lin Fong-Cheng , Tsai Yao-Chien , Lin Shun-Ku 
Published: June 2019

Abstract
Knee osteoarthritis is a degenerative disease occurring in elderly people worldwide. For severe knee osteoarthritis, total knee replacement is the final treatment option. Traditional Chinese medicine (TCM) is popular in Taiwan and has been shown to exert therapeutic effects on knee osteoarthritis. We investigated the long-term clinical effects of TCM for reducing the need for total knee replacement risk in patients with knee osteoarthritis.
We used the National Health Insurance Research Database to conduct a retrospective study of patients with knee osteoarthritis between 1997 and 2003 in Taiwan. Data from the date of diagnosis of knee osteoarthritis to total knee replacement were assessed using the Cox regression proportional hazards model, and the Kaplan–Meier survival curve was used to determine the association between total knee replacement risk and TCM use.
A total of 34,231 patients with knee osteoarthritis, who were diagnosed by orthopedic or rehabilitation physicians between 1997 and 2003 were included. Patients were categorized into 2 groups: 26,257 (76.7%) were TCM users and 7974 (23.3%) were TCM non-users. The mean follow-up period was 9.26 years. Multivariate regression demonstrated that using TCM may decrease the need for total knee replacement in patients with knee osteoarthritis (adjusted hazards ratio [aHR] = 0.69, 95% confidence interval [95% CI]: 0.64–0.77) compared with TCM non-users. A relationship between longer TCM use and reduced total knee replacement use was observed, especially in patients who used TCM for ≥120 days (aHR = 0.49, 95% CI: 0.42–0.56).
The results of this study suggested that TCM is associated with a reduced risk of total knee replacement in patients with knee osteoarthritis, with enhanced benefits from longer durations of TCM use.