bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD38-Mediated Immunosuppression as a Mechanism of Tumor Cell Escape from PD-1/PD-L1 Blockade
Authors: Chen Limo , Diao Lixia , Yang Yongbin , Yi Xiaohui , Rodriguez B. Leticia , Li Yanli , Villalobos Pamela A. , Cascone Tina , Liu Xi , Tan Lin , Lorenzi Philip L. , Huang Anfei , Zhao Qiang , Peng Di , Fradette Jared J. , Peng David H. , Ungewiss Christin , Roybal Jonathon , Tong Pan , Oba Junna , Skoulidis Ferdinandos , Peng Weiyi , Carter Brett W. , Gay Carl M. , Fan Youhong , Class Caleb A. , Zhu Jingfen , Rodriguez-Canales Jaime , Kawakami Masanori , Byers Lauren Averett , Woodman Scott E. , Papadimitrakopoulou Vassiliki A. , Dmitrovsky Ethan , Wang Jing , Ullrich Stephen E. , Wistuba Ignacio I. , Heymach John V. , Qin F. Xiao-Feng , Gibbons Don L. 
Published: July 2018

Abstract
Although treatment with immune checkpoint inhibitors provides promising benefit for patients with cancer, optimal use is encumbered by high resistance rates and requires a thorough understanding of resistance mechanisms. We observed that tumors treated with PD-1/PD-L1 blocking antibodies develop resistance through the upregulation of CD38, which is induced by all-trans retinoic acid and IFNβ in the tumor microenvironment. In vitro and in vivo studies demonstrate that CD38 inhibits CD8+ T-cell function via adenosine receptor signaling and that CD38 or adenosine receptor blockade are effective strategies to overcome the resistance. Large data sets of human tumors reveal expression of CD38 in a subset of tumors with high levels of basal or treatment-induced T-cell infiltration, where immune checkpoint therapies are thought to be most effective. These findings provide a novel mechanism of acquired resistance to immune checkpoint therapy and an opportunity to expand their efficacy in cancer treatment.
Significance: CD38 is a major mechanism of acquired resistance to PD-1/PD-L1 blockade, causing CD8+ T-cell suppression. Coinhibition of CD38 and PD-L1 improves antitumor immune response. Biomarker assessment in patient cohorts suggests that a combination strategy is applicable to a large percentage of patients in whom PD-1/PD-L1 blockade is currently indicated. Cancer Discov; 8(9); 1156–75. ©2018 AACR.
See related commentary by Mittal et al., p. 1066.
This article is highlighted in the In This Issue feature, p. 1047
Dia bonito pra chover: Escrita negra e poética da interpretação em Lívia Natália
Authors: Freitas Ricardo Oliveira de , Nunes Davi , Prado Thiago Martins 
Published: July 2018

Analisamos traços de intencionalidade e autoria na obra da escritora negra baiana Lívia Natália. Para tanto, tomamos o livro de poesia Dia bonito pra chover como material de análise. Utilizamos as teorias de interpretação do texto literário, com o debate sobre a intencionalidade da autoria e autonomia da linguagem poética na obra, como referencial teórico-metodológico. A análise objetiva articular uma crítica interpretativa voltada para escrita negra, para a consolidação do gênero literatura negra.
Prognostic Value of Serial Echocardiography in Hypoplastic Left Heart Syndrome
Authors: Son Jae Sung , James Adam , Fan Chun-Po Steve , Mertens Luc , McCrindle Brian W. , Manlhiot Cedric , Friedberg Mark K. 
Published: July 2018

Background:
Hypoplastic left heart syndrome (HLHS) carries a high mortality. The prognostic value of echocardiographic variables at presentation and the importance of serial data are poorly explored.

Methods and Results:

We retrospectively analyzed longitudinal clinical and echocardiographic parameters of children with hypoplastic left heart syndrome. The primary outcome was time to death or transplant after stage-1 surgery, right censored at stage 3 surgery, accounting for sequential surgical procedures. Univariable and multivariable analysis identified risk factors for transplant or mortality. Time-dependent trends in echo parameters stratified by patient survival were explored using nonparametric methods. In total 67 children with hypoplastic left heart syndrome were included. The 10-week, 20-week, and 1-year survival proportions were 77.6% (66–86), 68.7% (56–78), and 54.1% (41–65), respectively. At presentation, multivariable analysis identified a thicker interventricular septum (hazard ratio [HR], 1.64;
P
=0.007) to be associated with increased risk for transplant/death, whereas higher tricuspid valve annular planar systolic excursion z score (HR, 0.61;
P
=0.003) was associated with reduced risk of mortality/transplant. After stage-1, higher body surface area-indexed right ventricular end-systolic area (HR, 1.52;
P
=0.02), lower fractional area change (HR, 1.18;
P
=0.01), and qualitatively decreased right ventricular function (HR, 2.55;
P
=0.08) were associated with increased risk of transplant-free mortality, censored at stage 3. Higher body surface area-indexed right ventricular end-diastolic area (HR, 0.76;
P
=0.04) and better tricuspid valve annular planar systolic excursion z score (HR, 0.49;
P
=0.01) were associated with lower mortality/transplant. During follow-up, right ventricular dilation, dysfunction, and tricuspid regurgitation improved in transplant-free survivors and worsened in those transplanted or who died.

Conclusions:
Conventional echocardiographic parameters at presentation and during follow-up are potential markers for transplant-free survival in children with hypoplastic left heart syndrome.
Is There an Age When Myocardial Perfusion Imaging May No Longer Be Prognostically Useful?
Authors: Erthal Fernanda , Hossain Alomgir , Dorbala Sharmila , Shaw Leslee J. , Di Carli Marcelo F. , Merhige Michael E. , Williams Brent A. , Veledar Emir , Min James K. , Berman Daniel S. , deKemp Robert A. , Beanlands Rob S.B. , Chow Benjamin J.W. 
Published: July 2018

Background:
Heart disease continues to be the leading cause of death, and the prevalence of coronary artery disease is expected to increase as the population ages. It is important to understand the clinical utility of medical tests, or its lack thereof, in the aging population. The objective of this study was to understand the incremental prognostic value of positron emission tomographic (PET) myocardial perfusion imaging in the elderly (≥85 years of age).

Methods and Results:
A total of 3343 patients enrolled in a multicenter observational PET registry were analyzed. Participants were initially divided into 3 age categories: 65 to 74.9, 75 to 84.9, and ≥85 years of age and followed for all-cause death. Median follow-up time was 3 years. Of the total patient population, 248 patients (49% men) were ≥85 years old. When compared with younger patients, individuals ≥85 years had a higher prevalence of hypertension (79%) and a lower incidence of dyslipidemia (54%) and diabetes mellitus (24%). On multivariable analysis, %left ventricular stress defect and %left ventricular ischemia were predictors of patient outcome for those <85 years of age but was not statistically significant in those ≥85 years of age. The prognostic value of PET (%left ventricular stress defect and %left ventricular ischemia) appeared to decrease with advancing age.

Conclusions:
The elderly is a high-risk population irrespective of PET myocardial perfusion imaging results, and incremental prognostic value of PET myocardial perfusion imaging appears to wane in those ≥85 years of age. Although PET myocardial perfusion imaging may be diagnostically useful in the elderly, its prognostic value in this population requires further evaluation.
Quantification of Coronary Atherosclerosis in the Assessment of Coronary Artery Disease
Authors: Lee Sang-Eun , Sung Ji Min , Rizvi Asim , Lin Fay Y. , Kumar Amit , Hadamitzky Martin , Kim Yong-Jin , Conte Edoardo , Andreini Daniele , Pontone Gianluca , Budoff Matthew J. , Gottlieb Ilan , Lee Byoung Kwon , Chun Eun Ju , Cademartiri Filippo , Maffei Erica , Marques Hugo , Leipsic Jonathon A. , Shin Sanghoon , Hyun Choi Jung , Chinnaiyan Kavitha , Raff Gilbert , Virmani Renu , Samady Habib , Stone Peter H. , Berman Daniel S. , Narula Jagat , Shaw Leslee J. , Bax Jeroen J. , Min James K. , Chang Hyuk-Jae 
Published: July 2018

Background:
Diagnosis of coronary artery disease and management strategies have relied solely on the presence of diameter stenosis ≥50%. We assessed whether direct quantification of plaque burden (PB) and plaque characteristics assessed by coronary computed tomography angiography could provide additional value in terms of predicting rapid plaque progression.

Methods and Results:

From a 13-center, 7-country prospective observational registry, 1345 patients (60.4±9.4 years old; 57.1% male) who underwent repeated coronary computed tomography angiography >2 years apart were enrolled. For conventional angiographic analysis, the presence of stenosis ≥50%, number of vessel involved, segment involvement score, and the presence of high-risk plaque feature were determined. For quantitative analyses, PB and annual change in PB (△PB/y) in the entire coronary tree were assessed. Clinical outcomes (cardiac death, nonfatal myocardial infarction, and coronary revascularization) were recorded. Rapid progressors, defined as a patient with ≥median value of △PB/y (0.33%/y), were older, more frequently male, and had more clinical risk factors than nonrapid progressors (all
P
<0.05). After risk adjustment, addition of baseline PB improved prediction of rapid progression to each angiographic assessment of coronary artery disease, and the presence of high-risk plaque further improved the predictive performance (all
P
<0.001). For prediction of adverse outcomes, adding both baseline PB and △PB/y showed best predictive performance (C statistics, 0.763;
P
<0.001).

Conclusions:
Direct quantification of atherosclerotic PB in addition to conventional angiographic assessment of coronary artery disease might be beneficial for improving risk stratification of coronary artery disease.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02803411.
Increased Blood Pressure Variability Contributes to Worse Outcome After Intracerebral Hemorrhage
Authors: de Havenon Adam , Majersik Jennifer J. , Stoddard Gregory , Wong Ka-Ho , McNally J. Scott , Smith A. Gordon , Rost Natalia S. , Tirschwell David L. 
Published: July 2018

Background and Purpose—
Increased systolic blood pressure variability (BPV) is associated with worse outcome after acute ischemic stroke and may also have a negative impact after intracerebral hemorrhage. We sought to determine whether increased BPV was detrimental in the ATACH-2 (Antihypertensive Treatment of Acute Cerebral Hemorrhage II) trial.

Methods—
The primary outcome of our study was a 3-month follow-up modified Rankin Scale of 3 to 6, and the secondary outcome was a utility-weighted modified Rankin Scale. We calculated blood pressure mean and variability using systolic blood pressure from the acute period (2–24 hours postrandomization) and subacute period (days 2, 3, and 7).

Results—
The acute period included 913 patients and the subacute included 877. For 5 different statistical measures of systolic BPV, there was a consistent association between increased BPV and worse neurological outcome in both the acute and subacute periods. This association was not found for systolic blood pressure mean.

Conclusions—
In this secondary analysis of ATACH-2, we show that increased systolic BPV is associated with worse long-term neurological outcome. Additional research is needed to find techniques that allow early identification of patients with an expected elevation of BPV and to study pharmacological or protocol-based approaches to minimize BPV.
The Role of Hyperbaric Oxygen as Salvage Therapy for Sudden Sensorineural Hearing Loss
Authors: Almosnino Galit , Holm James R. , Schwartz Seth R. , Zeitler Daniel M. 
Published: July 2018

Objective: We sought to evaluate hearing outcomes after salvage therapy with hyperbaric oxygen (HBO2) for the treatment of sudden sensorineural hearing loss (SSNHL). Study Design: Matched control retrospective case series. Setting: Tertiary neurotology referral center. Patients: Thirty-six patients (>18 years) diagnosed with SSNHL. Intervention: Patients received initial therapy with oral and/or intratympanic (IT) steroids with an incomplete response. Eighteen patients underwent salvage therapy with IT steroids and HBO2 (group 1). Eighteen matched controls underwent salvage therapy with IT steroids alone (group 2). Main outcome measures: The main outcome measure was improvement in pure tone average (PTA) and word recognition score (WRS). Complications as a result of therapy were also monitored. Results: There were no significant differences in age, gender, or hearing between the 2 groups ( P > .05). There was no significant difference in mean post-treatment PTA between group 1 (60.3 dB) and group 2 (53.2 dB). There were no significant difference in mean post-treatment WRS between group 1 (42%) and group 2 (51%). Serviceable hearing was defined as a minimum WRS of 50%. Thirty-three percent in group 1 and 42% in group 2 went from nonserviceable hearing to serviceable hearing ( P > .05). PTA and WRS change scores were not significantly affected by age, gender, form of initial treatment, or pre-treatment PTA and WRS. Conclusion: The present study demonstrated no significant difference in hearing outcomes between patients receiving salvage therapy with HBO2 and IT steroids compared to patients receiving IT steroids alone. Larger, prospective randomized trials are needed to better define the role of HBO2 as salvage therapy for SSNHL.
A Clinical Comparison of Linear- and Surface Area–Based Methods of Measuring Glenoid Bone Loss
Authors: Bakshi Neil K. , Cibulas George A. , Sekiya Jon K. , Bedi Asheesh 
Published: July 2018

Background: The purpose of this study was to determine whether linear-based measurement significantly overestimates glenoid bone loss in comparison with surface area–based measurement in patients with recurrent anterior shoulder instability and glenoid bone loss. Hypothesis: Linear-based measurement will significantly overestimate glenoid bone loss in comparison with surface area–based measurement in patients with anterior shoulder instability and glenoid bone loss. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: Thirty patients with anterior shoulder instability underwent preoperative bilateral shoulder computed tomography (CT) scans. Three-dimensional CT (3D-CT) reconstruction with humeral head subtraction was performed to obtain an en face view of the 3D-CT glenoid. Glenoid bone loss was measured with the surface area and linear methods of measurement. Statistical analysis was performed with a paired 2-tailed t test. Results: Twenty-eight patients (5 female and 23 male; mean age, 25.1 years; age range, 15-58 years) were included in the study; 17 patients underwent a glenoid augmentation procedure, and 11 underwent arthroscopic Bankart repair. The mean percentage glenoid bone loss calculated with the surface area and linear methods was 12.8% ± 8.0% and 17.5% ± 9.7% ( P < .0001), respectively. For the 17 patients who underwent glenoid augmentation, mean percentage bone loss with the surface area and linear methods was 16.6% ± 7.9% and 23.0% ± 8.0% ( P < .0001), respectively. Conclusion: Linear measurement of glenoid bone loss significantly overestimates bone loss compared with surface area measurement in patients with anterior glenoid bony defects. These results indicate that these different methods cannot be used interchangeably and cannot be used with the same critical thresholds for glenoid bone loss.
In vivo tracking of intravenously injected mesenchymal stem cells in an Alzheimer’s animal model
Authors: Park Bok-Nam , Lim Tae Sung , Yoon Joon-Kee , An Young-Sil 
Published: July 2018

Purpose: The purpose of this study was to investigate how intravenously injected bone marrow-derived mesenchymal stem cells (BMSCs) are distributed in the body of an Alzheimer’s disease (AD) animal model. Methods: Stem cells were collected from bone marrow of mice and labeled with Indium-111 (111In). The 111In-labeled BMSCs were infused intravenously into 3×Tg-AD mice in the AD group and non-transgenic mice (B6129SF2/J) as controls. Biodistribution was evaluated with a gamma counter and gamma camera 24 and 48 h after injecting the stem cells. Results: A gamma count of the brain showed a higher distribution of labeled cells in the AD model than in the control group at 24 (p = .0004) and 48 h (p = .0016) after injection of the BMSCs. Similar results were observed by gamma camera imaging (i.e., brain uptake in the AD model was significantly higher than that in the control group). Among the other organs, uptake by the spleen was the highest in both groups. More BMSCs were found in the lungs of the control group than in those of the AD group. Conclusions: These results suggest that more intravenously infused BMSCs reached the brain in the AD model than in the control group, but the numbers of stem cells reaching the brain was very small.
Temporal association between antibiotic use and resistance in Klebsiella pneumoniae at a tertiary care hospital
Authors: Ryu Sukhyun , Klein Eili Y. , Chun Byung Chul 
Published: July 2018

Abstract
Background
β-Lactam/β-lactamase inhibitors (BLBLIs) were introduced into clinical practice as an alternative to carbapenems for treating multi-drug–resistant Klebsiella pneumoniae infections. However, little is known about the relationship between BLBLI treatment and antimicrobial resistance. In this study, we investigated the trends and the temporal association between antibiotic use and antimicrobial resistance in K. pneumoniae isolates obtained between 2012 and 2016.

Methods
Data regarding quarterly consumption (total number of prescriptions per quarter) of all BLBLIs, all third-generation cephalosporins, and all fluoroquinolones at a tertiary care hospital were obtained from the Korean Health Insurance Review and Assessment Service. Susceptibility data (isolation rate of antibiotic resistance per quarter) were obtained from the existing database of the same tertiary hospital. Regression analysis was used to analyze annual trends and cross-correlations to assess the temporal association on a quarterly basis between antibiotic consumption and antibiotic resistance in K. pneumoniae.

Results
The rate of resistance to piperacillin/tazobactam in K. pneumoniae significantly increased over the study period (p < 0.01). The consumption of all BLBLIs was also found to be significantly correlated with the rate of resistance to piperacillin/tazobactam (β = 0.66; p < 0.01), ceftazidime (β = 0.54; p = 0.02), and levofloxacin (β = − 0.60; p = 0.01) with two-quarter lags. Furthermore, the consumption of all third-generation cephalosporins was significantly correlated with rates of K. pneumoniae resistance to ceftazidime (β = 0.64; p < 0.01) with a two-quarter lag and levofloxacin (β = 0.50; p = 0.03) with a quarter lag. The consumption of all fluoroquinolones correlated with resistance rates to ceftazidime (β = 0.14; p < 0.01) with a two-quarter lag.

Conclusions
The rate of resistance to piperacillin/tazobactam in K. pneumoniae increased significantly over the study period and was significantly correlated with BLBLI consumption. While BLBLIs can potentially be utilized as an alternative to carbapenems, our findings reinforce concerns of resistance to these drugs. Further research is needed to understand the implications on resistance of utilizing BLBLIs as a carbapenem-sparing option.
SEMÂNTICA PARA PEJORATIVOS: CONTRA-ARGUMENTOS À INOCÊNCIA SEMÂNTICA
Authors: Lindemann John Lennon 
Published: July 2018

Resumo: Os pejorativos tem sido objeto de uma crescente literatura em filosofia. Hom e May (2013) defendem a tese da Inocência Semântica para explicar a força depreciativa dos pejorativos, tese que recebeu ataques de Sennet e Copp (2014). O objetivo deste artigo é apresentar contribuições a esta discussão, defendendo a tese da Inocência Semântica dos ataques recebidos de Sennet e Copp (2014), mas apresentando um novo argumento contra suas pretensões, mostrando que a tese da Inocência Semântica falha em reconhecer o caráter depreciativo de injurias cuja contraparte neutra seja falsa.Palavras-chave: Semântica. Pejorativos. Injúrias.Abstract: The pejorative have been the object of a growing literature in philosophy. Hom and May (2013) defend the Semantic Innocence thesis to explain a depreciative force of the pejoratives, receiving attacks from Sennet and Copp (2014). The purpose of this article is to present contributions to this discussion, defending the Semantic Innocence thesis of the attacks received from Sennet and Copp (2014), but presenting a new argument against its pretensions, showing that the Semantic Innocence thesis fails to recognize the derogatory character of insults whose neutral counterpart is false. Keywords: Semantics. Pejorative. Injuries.
THE EFFICIENCY OF BIOLOGICAL THERAPY AND THE FEATURES OF HUMORAL IMMUNITY IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Mesnyankina A. A. , Solovyev S. K. , Aseeva E. A. , Nasonov E. L. 
Published: July 2018

Objective: to investigate the effect of various biological agents (BAs), including combined treatment with rituximab (RTM) and belimumab (BLM), on the activity of systemic lupus erythematosus (SLE) and to evaluate their efficacy and impact on some parameters of humoral immunity.Subjects and methods. BAs were prescribed to 54 patients with a reliable diagnosis of SLE with high and medium activity according to SLEDAI-2K; 40 of them received RTM, 7 – BLM; 7 – combined therapy with RTM and BLM. Clinical and laboratory examinations were made in all the patients at the time of their inclusion and then every 3 months during a year. The results were assessed using SLEDAI-2K, BILAG index, Lupus Erythematosus National Assessment (SELENA)-SLEDAI Flare index (SFI) (a moderate, severe exacerbation), and SLE Responder Index (SRI).Results and discussion. At 3, 6, and 12 months after start of therapy, the use of BAs in all the patients resulted in a disease activity reduction. It was statistically significant (p < 0.00001) in the RTM group; and no statistical analysis was carried out in the BLM and RTM+BLM groups due to the small numbers of patients. At the same time, there was a progressive decrease in the levels of anti-double-stranded DNA (ds-DNA) antibodies (Abs) and an increase in the concentration of the complement fractions C3 and C4 in the RTM and RTM+BLM groups (p < 0.05) at one-year follow-up. After 12 months of therapy with BAs, there was a decrease in IgG (p < 0.02) and IgM (p < 0.03) levels; but overall it remained within the reference ranges. Prior to therapy, irreversible organ damages were recorded in 23 (42.6%) of the 54 patients. The increased damage index at 12 month was observed only in patients receiving RTM, which is probably due to the use of higher-dose glucocorticoids.Conclusion. All three methods of therapy with BAs in SLE patients demonstrated good efficiency shown as a significant decrease in clinical and laboratory activity measures that were assessed by SLEDAI-2K and the levels of anti-ds-DNA and complement components C3 and C4. The decrease in immunoglobulin levels did not go beyond the reference values. Therapy with BLM and RTM+BLM allowed for managing patients with the low and average doses of oral glucocorticoids, which contributed to the reduction of not only the activity, but also risk of irreversible organ damages.