bluuebunny/crossref_metadata_2025_split huggingface dataset:
The PET-Tracer 89Zr-Df-IAB22M2C Enables Monitoring of Intratumoral CD8 T-cell Infiltrates in Tumor-Bearing Humanized Mice after T-cell Bispecific Antibody Treatment
Authors: Griessinger Christoph M. , Olafsen Tove , Mascioni Alessandro , Jiang Ziyue Karen , Zamilpa Charles , Jia Fang , Torgov Michael , Romero Jason M. , Marchioni Filippo , Satpayev Daulet , Lee Chenyu , Zhang Green , Nayak Tapan K. , Pincha Mudita , Amann Maria , Mohan Preethi L.B. , Richard Marine , Nicolini Valeria G. , Sam Johannes , Claus Christina , Ferrara Claudia , Brünker Peter , Bacac Marina , Umana Pablo , Rüttinger Dominik , Wilson Ian A. , Gudas Jean , Klein Christian , Tessier Jean J.L. 
Published: May 2020

Abstract

CD8-expressing T cells are the main effector cells in cancer immunotherapy. Treatment-induced changes in intratumoral CD8+ T cells may represent a biomarker to identify patients responding to cancer immunotherapy. Here, we have used a 89Zr-radiolabeled human CD8-specific minibody (89Zr-Df-IAB22M2C) to monitor CD8+ T-cell tumor infiltrates by PET. The ability of this tracer to quantify CD8+ T-cell tumor infiltrates was evaluated in preclinical studies following single-agent treatment with FOLR1-T-cell bispecific (TCB) antibody and combination therapy of CEA-TCB (RG7802) and CEA-targeted 4-1BB agonist CEA-4-1BBL. In vitro cytotoxicity assays with peripheral blood mononuclear cells and CEA-expressing MKN-45 gastric or FOLR1-expressing HeLa cervical cancer cells confirmed noninterference of the anti-CD8-PET-tracer with the mode of action of CEA-TCB/CEA-4-1BBL and FOLR1-TCB at relevant doses. In vivo, the extent of tumor regression induced by combination treatment with CEA-TCB/CEA-4-1BBL in MKN-45 tumor–bearing humanized mice correlated with intratumoral CD8+ T-cell infiltration. This was detectable by 89Zr-IAB22M2C-PET and γ-counting. Similarly, single-agent treatment with FOLR1-TCB induced strong CD8+ T-cell infiltration in HeLa tumors, where 89Zr-Df-IAB22M2C again was able to detect CD8 tumor infiltrates. CD8-IHC confirmed the PET imaging results. Taken together, the anti-CD8-minibody 89Zr-Df-IAB22M2C revealed a high sensitivity for the detection of intratumoral CD8+ T-cell infiltrates upon either single or combination treatment with TCB antibody–based fusion proteins. These results provide further evidence that the anti-CD8 tracer, which is currently in clinical phase II, is a promising monitoring tool for intratumoral CD8+ T cells in patients treated with cancer immunotherapy.

Significance:
Monitoring the pharmacodynamic activity of cancer immunotherapy with novel molecular imaging tools such as 89Zr-Df-IAB22M2C for PET imaging is of prime importance to identify patients responding early to cancer immunotherapy.
The NKG2A–HLA-E Axis as a Novel Checkpoint in the Tumor Microenvironment
Authors: Borst Linda , van der Burg Sjoerd H. , van Hall Thorbald 
Published: May 2020

AbstractThe success of checkpoint blockade therapy revolutionized cancer treatment. However, we need to increase the fraction of responding patients and overcome acquired resistance to these therapies. Recently, the inhibitory receptor NKG2A received attention as a new kid on the block of immune checkpoints. This receptor is selectively expressed on cytotoxic lymphocytes, including natural killer cells and CD8 T cells, and NKG2A+ T cells are preferentially residing in tissues, like the tumor microenvironment. Its ligand, histocompatibility leucocyte antigen E (HLA-E), is a conserved nonclassical HLA class I molecule that binds a limited peptide repertoire and its expression is commonly detected in human cancer. NKG2A blockade as a standalone therapy appears poorly effective in mouse tumor models, however, in the presence of activated T cells, for example, induced by PD-1/PD-L1 blockade or cancer vaccines, exerts strongly enhanced efficacy. Clinical trials demonstrated safety of the humanized NKG2A-blocking antibody, monalizumab, and first results of phase II trials demonstrate encouraging durable response rates. Further development of this axis is clearly warranted.
Lymphatic and Immune Cell Cross-Talk Regulates Cardiac Recovery After Experimental Myocardial Infarction
Authors: Houssari Mahmoud , Dumesnil Anais , Tardif Virginie , Kivelä Riikka , Pizzinat Nathalie , Boukhalfa Ines , Godefroy David , Schapman Damien , Hemanthakumar Karthik A. , Bizou Mathilde , Henry Jean-Paul , Renet Sylvanie , Riou Gaetan , Rondeaux Julie , Anouar Youssef , Adriouch Sahil , Fraineau Sylvain , Alitalo Kari , Richard Vincent , Mulder Paul , Brakenhielm Ebba 
Published: May 2020

Objective:
Lymphatics play an essential pathophysiological role in promoting fluid and immune cell tissue clearance. Conversely, immune cells may influence lymphatic function and remodeling. Recently, cardiac lymphangiogenesis has been proposed as a therapeutic target to prevent heart failure after myocardial infarction (MI). We investigated the effects of gene therapy to modulate cardiac lymphangiogenesis post-MI in rodents. Second, we determined the impact of cardiac-infiltrating T cells on lymphatic remodeling in the heart.

Approach and Results:

Comparing adenoviral versus adeno-associated viral gene delivery in mice, we found that only sustained VEGF (vascular endothelial growth factor)-C
C156S
therapy, achieved by adeno-associated viral vectors, increased cardiac lymphangiogenesis, and led to reduced cardiac inflammation and dysfunction by 3 weeks post-MI. Conversely, inhibition of VEGF-C/-D signaling, through adeno-associated viral delivery of soluble VEGFR3 (vascular endothelial growth factor receptor 3), limited infarct lymphangiogenesis. Unexpectedly, this treatment improved cardiac function post-MI in both mice and rats, linked to reduced infarct thinning due to acute suppression of T-cell infiltration. Finally, using pharmacological, genetic, and antibody-mediated prevention of cardiac T-cell recruitment in mice, we discovered that both CD4
+
and CD8
+
T cells potently suppress, in part through interferon-γ, cardiac lymphangiogenesis post-MI.

Conclusions:

We show that resolution of cardiac inflammation after MI may be accelerated by therapeutic lymphangiogenesis based on adeno-associated viral gene delivery of VEGF-C
C156S
. Conversely, our work uncovers a major negative role of cardiac-recruited T cells on lymphatic remodeling. Our results give new insight into the interconnection between immune cells and lymphatics in orchestration of cardiac repair after injury.
Relative Costs of Surgical and Transcatheter Aortic Valve Replacement and Medical Therapy
Authors: Goldsweig Andrew M. , Tak Hyo Jung , Chen Li-Wu , Aronow Herbert D. , Shah Binita , Kolte Dhaval , Desai Nihar R. , Szerlip Molly , Velagapudi Poonam , Abbott J. Dawn 
Published: May 2020

Background:
The number of patients treated for aortic valve disease in the United States is increasing rapidly. Transcatheter aortic valve replacement (TAVR) is supplanting surgical aortic valve replacement (SAVR) and medical therapy (MT). The economic implications of these trends are unknown. Therefore, we undertook to determine the costs, inpatient days, and number of admissions associated with treating aortic valve disease with SAVR, TAVR, or MT.

Methods:
Using the Nationwide Readmissions Database, we identified patients with aortic valve disease admitted 2012 to 2016 for SAVR, TAVR, and disease symptoms (congestive heart failure, unstable angina, non–ST-elevation myocardial infarction, syncope). Patients not undergoing SAVR or TAVR were classified as receiving MT. Beginning with the index admission, we estimated inpatient costs, days, and admissions over 6 months.

Results:

Among 190 563 patients with aortic valve disease, the average aggregate 6-month inpatient costs were $59 743 for SAVR, $64 395 for TAVR, and $23 460 for MT. Mean index admission was longer for SAVR (10.0 days) than for TAVR (7.0 day) or MT (5.3 days), but the average number of unplanned readmission inpatient days was 2.0 for SAVR, 3.0 for TAVR, and 4.3 for MT; the average number of total admissions was 1.3 for SAVR, 1.5 for TAVR, and 1.7 for MT (
P
<0.01 for all). TAVR index admission costs decreased over time to become similar to SAVR costs by 2016.

Conclusions:
Aggregate costs were higher for TAVR than SAVR and were significantly more expensive than MT alone. However, TAVR costs decreased over time while SAVR and MT costs remained unchanged.
Role of the GLUT1 Glucose Transporter in Postnatal CNS Angiogenesis and Blood-Brain Barrier Integrity
Authors: Veys Koen , Fan Zheng , Ghobrial Moheb , Bouché Ann , García-Caballero Melissa , Vriens Kim , Conchinha Nadine Vasconcelos , Seuwen Aline , Schlegel Felix , Gorski Tatiane , Crabbé Melissa , Gilardoni Paola , Ardicoglu Raphaela , Schaffenrath Johanna , Casteels Cindy , De Smet Gino , Smolders Ilse , Van Laere Koen , Abel E. Dale , Fendt Sarah-Maria , Schroeter Aileen , Kalucka Joanna , Cantelmo Anna Rita , Wälchli Thomas , Keller Annika , Carmeliet Peter , De Bock Katrien 
Published: May 2020

Rationale:

Endothelial cells (ECs) are highly glycolytic and generate the majority of their energy via the breakdown of glucose to lactate. At the same time, a main role of ECs is to allow the transport of glucose to the surrounding tissues. GLUT1 (glucose transporter isoform 1/
Slc2a1
) is highly expressed in ECs of the central nervous system (CNS) and is often implicated in blood-brain barrier (BBB) dysfunction, but whether and how GLUT1 controls EC metabolism and function is poorly understood.

Objective:
We evaluated the role of GLUT1 in endothelial metabolism and function during postnatal CNS development as well as at the adult BBB.

Methods and Results:
Inhibition of GLUT1 decreases EC glucose uptake and glycolysis, leading to energy depletion and the activation of the cellular energy sensor AMPK (AMP-activated protein kinase), and decreases EC proliferation without affecting migration. Deletion of GLUT1 from the developing postnatal retinal endothelium reduces retinal EC proliferation and lowers vascular outgrowth, without affecting the number of tip cells. In contrast, in the brain, we observed a lower number of tip cells in addition to reduced brain EC proliferation, indicating that within the CNS, organotypic differences in EC metabolism exist. Interestingly, when ECs become quiescent, endothelial glycolysis is repressed, and GLUT1 expression increases in a Notch-dependent fashion. GLUT1 deletion from quiescent adult ECs leads to severe seizures, accompanied by neuronal loss and CNS inflammation. Strikingly, this does not coincide with BBB leakiness, altered expression of genes crucial for BBB barrier functioning nor reduced vascular function. Instead, we found a selective activation of inflammatory and extracellular matrix related gene sets.

Conclusions:
GLUT1 is the main glucose transporter in ECs and becomes uncoupled from glycolysis during quiescence in a Notch-dependent manner. It is crucial for developmental CNS angiogenesis and adult CNS homeostasis but does not affect BBB barrier function.
Exploring Factors Contributing to Race Differences in Poststroke Disability
Authors: Skolarus Lesli E. , Feng Chunyang , Burke James F. 
Published: May 2020

Background and Purpose—
Cross sectional analyses have found large race differences in poststroke disability, yet these analyses do not account for prestroke disability, hospitalization factors, postacute care, transitions, or mortality. In this context, we explore mortality, nursing home placement, and disability in a longitudinal analysis of older stroke survivors who survived at least 90 days poststroke.

Methods—
A prospective cohort of black or white stroke survivors from the National Health and Aging Trends Study (2009–2016) linked to Medicare were used. Disability was assessed during in-person interviews with validated scales (0–7). We used cox proportional hazards models to separately assess mortality and nursing home admission adjusting for age, sex, sociodemographics (marital status, education, income, insurance status, social network size), comorbidities, hospitalization factors, postacute care, and 90-day readmissions. To estimate racial differences in disability, we used a multilevel linear regression model initially adjusting for age and sex and then compared with a model adjusted for sociodemographics, comorbidities, hospitalization factors, postacute care, and 90-day readmissions.

Results—

There were 282 stroke survivors, of which 76 (12.6%) were black. There were no race differences in long-term mortality (hazard ratio for black, 1.2 [95% CI, 0.7–2.2];
P
=0.5) or nursing home placement (hazard ratio for black, 0.7 [95% CI, 0.2–2.4];
P
=0.5). The largest race differences in disability were observed immediately prestroke, estimated age- and sex-adjusted activity limitations were (2.6 [2.0–3.2] in blacks versus 1.4 [1.0–1.8] in whites, mean difference, 1.2 [0.5–1.9],
P
<0.001) and immediately poststroke (2.6 [2.0–3.3] in blacks versus 1.7 [1.2–2.1] in whites, mean difference, 1.0 [0.2–1.7],
P
<0.01). Full adjustment did not substantially change the associations between race and disability.

Conclusions—
Race differences in nursing home placement, long-term mortality, sociodemographics, comorbidities, hospitalization factors, postacute care, and readmissions are unlikely to be large contributors to race differences in poststroke disability. Further research is needed to understand the drivers of race differences in poststroke disability.
Association of Prediabetes and Type 2 Diabetes With Cognitive Function After Stroke
Authors: Lo Jessica W. , Crawford John D. , Samaras Katherine , Desmond David W. , Köhler Sebastian , Staals Julie , Verhey Frans R.J. , Bae Hee-Joon , Lee Keon-Joo , Kim Beom Joon , Bordet Régis , Cordonnier Charlotte , Dondaine Thibaut , Mendyk Anne-Marie , Lee Byung-Chul , Yu Kyung-Ho , Lim Jae-Sung , Kandiah Nagaendran , Chander Russell J. , Yatawara Chathuri , Lipnicki Darren M. , Sachdev Perminder S. ,   for the STROKOG Collaboration*
Published: May 2020

Background and Purpose—
Type 2 diabetes mellitus (T2D) is associated with cognitive impairment and an increased risk of dementia, but the association between prediabetes and cognitive impairment is less clear, particularly in a setting of major cerebrovascular events. This article examines the impact of impaired fasting glucose and T2D on cognitive performance in a stroke population.

Methods—

Seven international observational studies from the STROKOG (Stroke and Cognition) consortium (n=1601; mean age, 66.0 years; 70% Asian, 26% white, and 2.6% African American) were included. Fasting glucose level (FGL) during hospitalization was used to define 3 groups, T2D (FGL ≥7.0 mmol/L), impaired fasting glucose (FGL 6.1–6.9 mmol/L), and normal (FGL <6.1 mmol/L), and a history of diabetes mellitus and the use of a diabetes mellitus medication were also used to support a diagnosis of T2D. Domain and global cognition
Z
scores were derived from standardized neuropsychological test scores. The cross-sectional association between glucose status and cognitive performance at 3 to 6 months poststroke was examined using linear mixed models, adjusting for age, sex, education, stroke type, ethnicity, and vascular risk factors.

Results—

Patients with T2D had significantly poorer performance in global cognition (SD, −0.59 [95% CI, −0.82 to −0.36];
P
<0.001) and in all domains compared with patients with normal FGL. There was no significant difference between impaired fasting glucose patients and those with normal FGL in global cognition (SD, −0.10 [95% CI, −0.45 to 0.24];
P
=0.55) or in any cognitive domain.

Conclusions—
Diabetes mellitus, but not prediabetes, is associated with poorer cognitive performance in patients 3 to 6 months after stroke.
Computed Tomography Perfusion After Thrombectomy
Authors: Rubiera Marta , Garcia-Tornel Alvaro , Olivé-Gadea Marta , Campos Daniel , Requena Manuel , Vert Carla , Pagola Jorge , Rodriguez-Luna David , Muchada Marian , Boned Sandra , Rodriguez-Villatoro Noelia , Juega Jesus , Deck Matias , Sanjuan Estela , Hernandez David , Piñana Carlos , Tomasello Alejandro , Molina Carlos A. , Ribo Marc 
Published: May 2020

Background and Purpose—
Despite recanalization, almost 50% of patients undergoing endovascular treatment (EVT) experience poor outcome. We aim to evaluate the value of computed tomography perfusion as immediate outcome predictor postendovascular treatment.

Methods—
Consecutive patients receiving endovascular treatment who achieved recanalization (modified Thrombolysis in Cerebral Ischemia [mTICI] 2a-3) underwent computed tomography perfusion within 30 minutes from recanalization (CTPpost). Hypoperfusion was defined as the Tmax>6 second volume; hyperperfusion as visually increased cerebral blood flow/cerebral blood volume with reduced Tmax compared with unaffected hemisphere. Dramatic clinical recovery (DCR) was defined as 24-hour National Institutes of Health Stroke Scale score ≤2 or ≥8 points drop. Delayed recovery was defined as no-DCR with favorable outcome (modified Rankin Scale score 0–2) at 3 months.

Results—

We included 151 patients: median National Institutes of Health Stroke Scale score 16 (interquartile range, 10–21), median admission ASPECTS 9 (interquartile range, 8–10). Final recanalization was the following: mTICI2a 11 (7.3%), mTICI2b 46 (30.5%), and mTICI3 94 (62.3%). On CTPpost, 80 (52.9%) patients showed hypoperfusion (median Tmax>6 seconds: 4 cc [0–25]) and 32 (21.2%) hyperperfusion. There was an association between final TICI and CTPpost hypoperfusion(median Tmax>6: 91 [56–117], 15 [0–37.5], and 0 [0–7] cc, for mTICI 2a, 2b, and 3, respectively,
P
<0.01). Smaller hypoperfusion volumes on CTPpost were observed in patients with DCR (0 cc [0–13] versus non-DCR 8 cc [0–56];
P
<0.01) or favorable outcome (modified Rankin Scale score 0–2: 0 cc [0–13] versus 7 [0–56] cc;
P
<0.01). No associations were detected with hyperperfusion pattern. An hypoperfusion volume <3.5 cc emerged as independent predictor of DCR (OR, 4.1 [95% CI, 2.0–8.3];
P
<0.01) and 3 months favorable outcome (OR, 3.5 [95% CI, 1.6–7.8];
P
<0.01).

Conclusions—
Hypoperfusion on CTPpost constitutes an immediate accurate surrogate marker of success after endovascular treatment and identifies those patients with delayed recovery and favorable outcome.
Mechanical Thrombectomy for Tandem Vertebrobasilar Stroke
Authors: Baik Sung Hyun , Jung Cheolkyu , Kim Byung Moon , Kim Dong Joon 
Published: May 2020

Background and Purpose—
Tandem vertebrobasilar strokes are not well-known causes of posterior circulation stroke. The purpose of this study was to investigate the characteristics and outcome of mechanical thrombectomy in patients with tandem vertebrobasilar stroke.

Methods—
Acute basilar artery occlusion patients with tandem vertebral artery (VA) stenosis/occlusion who underwent mechanical thrombectomy were retrospectively analyzed. Concomitant tandem VA steno-occlusion was defined as severe stenosis/occlusion of the extracranial VA with impaired flow. Clinical/angiographic characteristics, recanalization rate, procedure time, and clinical outcome were evaluated with comparisons according to the treatment strategy.

Results—

Tandem vertebrobasilar occlusion was identified in 24.6% (55 of 224) of the acute basilar artery occlusion patients. Overall successful recanalization and good clinical outcome was achieved in 87.2% (48 of 55) and 30.9% (17 of 55) of the patients. There were no significant differences in procedure time, recanalization rate, and clinical outcome in comparisons of the VA access route selection or angioplasty of the tandem VA lesion. Two patients developed short-term recurrent basilar artery occlusion when angioplasty of the tandem VA lesion was not performed. Good clinical outcome was more likely with lower baseline National Institutes of Health Stroke Scale score (odds ratio, 0.87 [95% CI, 0.787–0.961];
P
=0.006) and short onset-to-recanalization time (odds ratio, 0.993 [95% CI, 0.987–0.999];
P
=0.03).

Conclusions—
Tandem vertebrobasilar occlusion may be a frequent pathological mechanism of posterior circulation stroke. Good outcome may be achieved by strategic choice of the access route and selective angioplasty of the tandem VA lesion.
Are All Four-Day School Weeks Created Equal? A National Assessment of Four-Day School Week Policy Adoption and Implementation
Authors: Thompson Paul N. , Gunter Katherine , Schuna, Jr. John M. , Tomayko Emily J. 
Published: May 2020

Abstract
Four-day school weeks are used in over 1,600 schools across twenty-four states but little is known about adoption and implementation of these types of school calendars. Through examinations of school calendars and correspondence with school districts, we have compiled the most complete four-day school week dataset to date. We use this unique database to conduct a comprehensive analysis of four-day school week policy adoption and implementation. We find adoption of four-day school weeks is often financially motivated and has generally remained a small, rural district phenomenon. These schedules feature a day off once a week—often Friday—with increased time in school on each of the remaining four school days that, on average, is nearly an hour longer than the national average among five-day schools. Four-day school week schedules average only 148 school days per year, resulting in less time in school than the national average for five-day schools (180 days per year) despite the longer school days. Substantial heterogeneity exists in the structure of these schedules across states, which may help explain differential four-day school week effects on student outcomes across institutional settings in the previous literature.
Efficacy of entomopathogenic nematodes for the control of white grub, Anomala corpulenta Motschulsky, in laboratory and field
Authors: Guo Wenxiu , Zhao Guoyu , Wang Congli , Zhou Xianhong , Zhai Yifan , Men Xingyuan , Yu Yi 
Published: May 2020

Summary
Anomala corpulenta is one of the major white grubs that cause serious damages in peanut production. To develop an environmentally friendly method to control A. corpulenta larvae, the efficacy of species of entomopathogenic nematodes (EPN), application rate and larval stage against A. corpulenta were determined. Results showed that Steinernema longicaudum X-7 and S. glaseri B-4-1 were the most virulent species, which caused 77.8 and 84.4% corrected mortalities of the 2nd instar larvae at 25°C 14 days after treatments. Corrected mortalities of A. corpulenta caused by EPN were significantly affected by EPN application rate. A decrease but no significant difference in susceptibility from the 2nd to the 3rd instar was observed for the test EPN species S. longicaudum, S. glaseri and Heterorhabditis bacteriophora. The field experiments indicated that S. longicaudum and S. glaseri applied at a relatively high rate (⩾5.0 × 103 infective juveniles (IJ) plant−1, i.e., 7.5 × 108 IJ ha−1) were able to provide not only control efficacy against A. corpulenta with ⩾92.7% reduction of larvae and ⩽5.06% of damaged pods, and the peanut yield increase was as good as phoxim, but also gave better control persistency compared to phoxim. Our findings indicated that EPN could be an effective strategy for the management of A. corpulenta in peanut fields.