bluuebunny/crossref_metadata_2025_split huggingface dataset:
Some properties of n-multiply σ-local formations of finite groups
Authors: Safonova Inna N. 
Published: October 2021

All groups under consideration are finite. Let [Formula: see text] be some partition of the set of all primes [Formula: see text], [Formula: see text] be a group, and [Formula: see text] be a class of groups. Then, [Formula: see text] and [Formula: see text] A function [Formula: see text] of the form [Formula: see text] is called a formation [Formula: see text]-function. For any formation [Formula: see text]-function [Formula: see text] the class [Formula: see text] is defined as follows: [Formula: see text] [Formula: see text] If for some formation [Formula: see text]-function [Formula: see text] we have [Formula: see text] then the class [Formula: see text] is called [Formula: see text]-local and [Formula: see text] is called a [Formula: see text]-local definition of [Formula: see text] Every formation is called 0-multiply [Formula: see text]-local. For [Formula: see text] a formation [Formula: see text] is called [Formula: see text]-multiply [Formula: see text]-local provided either [Formula: see text] is the class of all identity groups or [Formula: see text] where [Formula: see text] is [Formula: see text]-multiply [Formula: see text]-local for all [Formula: see text] Let [Formula: see text] be a set of subgroups of [Formula: see text] such that [Formula: see text]. Then, [Formula: see text] is called a subgroup functor if for every epimorphism [Formula: see text] : [Formula: see text] and any groups [Formula: see text] and [Formula: see text] we have [Formula: see text] and [Formula: see text]. A class of groups [Formula: see text] is called [Formula: see text]-closed if [Formula: see text] for all [Formula: see text]. In this paper, we study the properties of [Formula: see text]-closed [Formula: see text]-multiply [Formula: see text]-local formations generated by some set of groups. In particular, we obtained a description of the smallest [Formula: see text]-local definition of such formation, we also prove that [Formula: see text]-closed [Formula: see text]-multiply [Formula: see text]-local formation [Formula: see text] is one-generated if and only if [Formula: see text] is finite and [Formula: see text] have a integrated [Formula: see text]-local definition [Formula: see text] such that [Formula: see text] is a one-generated [Formula: see text]-closed [Formula: see text]-multiply [Formula: see text]-local formation for all [Formula: see text]. In addition, we prove that the class of all [Formula: see text]-closed one-generated [Formula: see text]-multiply [Formula: see text]-local formations coincides with the class of all one-generated [Formula: see text]-closed [Formula: see text]-multiply [Formula: see text]-local formations.
Inhibition of PIM Kinases in DLBCL Targets MYC Transcriptional Program and Augments the Efficacy of Anti-CD20 Antibodies
Authors: Szydłowski Maciej , Garbicz Filip , Jabłońska Ewa , Górniak Patryk , Komar Dorota , Pyrzyńska Beata , Bojarczuk Kamil , Prochorec-Sobieszek Monika , Szumera-Ciećkiewicz Anna , Rymkiewicz Grzegorz , Cybulska Magdalena , Statkiewicz Małgorzata , Gajewska Marta , Mikula Michał , Gołas Aniela , Domagała Joanna , Winiarska Magdalena , Graczyk-Jarzynka Agnieszka , Białopiotrowicz Emilia , Polak Anna , Barankiewicz Joanna , Puła Bartosz , Pawlak Michał , Nowis Dominika , Golab Jakub , Tomirotti Andrea M. , Brzózka Krzysztof , Pacheco-Blanco Mariana , Kupcova Kristyna , Green Michael R. , Havranek Ondrej , Chapuy Bjoern , Juszczyński Przemysław 
Published: October 2021

Abstract

The family of PIM serine/threonine kinases includes three highly conserved oncogenes, PIM1, PIM2, and PIM3, which regulate multiple prosurvival pathways and cooperate with other oncogenes such as MYC. Recent genomic CRISPR-Cas9 screens further highlighted oncogenic functions of PIMs in diffuse large B-cell lymphoma (DLBCL) cells, justifying the development of small-molecule PIM inhibitors and therapeutic targeting of PIM kinases in lymphomas. However, detailed consequences of PIM inhibition in DLBCL remain undefined. Using chemical and genetic PIM blockade, we comprehensively characterized PIM kinase–associated prosurvival functions in DLBCL and the mechanisms of PIM inhibition–induced toxicity. Treatment of DLBCL cells with SEL24/MEN1703, a pan-PIM inhibitor in clinical development, decreased BAD phosphorylation and cap-dependent protein translation, reduced MCL1 expression, and induced apoptosis. PIM kinases were tightly coexpressed with MYC in diagnostic DLBCL biopsies, and PIM inhibition in cell lines and patient-derived primary lymphoma cells decreased MYC levels as well as expression of multiple MYC-dependent genes, including PLK1. Chemical and genetic PIM inhibition upregulated surface CD20 levels in an MYC-dependent fashion. Consistently, MEN1703 and other clinically available pan-PIM inhibitors synergized with the anti-CD20 monoclonal antibody rituximab in vitro, increasing complement-dependent cytotoxicity and antibody-mediated phagocytosis. Combined treatment with PIM inhibitor and rituximab suppressed tumor growth in lymphoma xenografts more efficiently than either drug alone. Taken together, these results show that targeting PIM in DLBCL exhibits pleiotropic effects that combine direct cytotoxicity with potentiated susceptibility to anti-CD20 antibodies, justifying further clinical development of such combinatorial strategies.

Significance:
These findings demonstrate that inhibition of PIM induces DLBCL cell death via MYC-dependent and -independent mechanisms and enhances the therapeutic response to anti-CD20 antibodies by increasing CD20 expression.
Hyperpolarized Carbon-13 MRI for Early Response Assessment of Neoadjuvant Chemotherapy in Breast Cancer Patients
Authors: Woitek Ramona , McLean Mary A. , Ursprung Stephan , Rueda Oscar M. , Manzano Garcia Raquel , Locke Matthew J. , Beer Lucian , Baxter Gabrielle , Rundo Leonardo , Provenzano Elena , Kaggie Joshua , Patterson Andrew , Frary Amy , Field-Rayner Johanna , Papalouka Vasiliki , Kane Justine , Benjamin Arnold J.V. , Gill Andrew B. , Priest Andrew N. , Lewis David Y. , Russell Roslin , Grimmer Ashley , White Brian , Latimer-Bowman Beth , Patterson Ilse , Schiller Amy , Carmo Bruno , Slough Rhys , Lanz Titus , Wason James , Schulte Rolf F. , Chin Suet-Feung , Graves Martin J. , Gilbert Fiona J. , Abraham Jean E. , Caldas Carlos , Brindle Kevin M. , Sala Evis , Gallagher Ferdia A. 
Published: October 2021

AbstractHyperpolarized 13C-MRI is an emerging tool for probing tissue metabolism by measuring 13C-label exchange between intravenously injected hyperpolarized [1–13C]pyruvate and endogenous tissue lactate. Here, we demonstrate that hyperpolarized 13C-MRI can be used to detect early response to neoadjuvant therapy in breast cancer. Seven patients underwent multiparametric 1H-MRI and hyperpolarized 13C-MRI before and 7–11 days after commencing treatment. An increase in the lactate-to-pyruvate ratio of approximately 20% identified three patients who, following 5–6 cycles of treatment, showed pathological complete response. This ratio correlated with gene expression of the pyruvate transporter MCT1 and lactate dehydrogenase A (LDHA), the enzyme catalyzing label exchange between pyruvate and lactate. Analysis of approximately 2,000 breast tumors showed that overexpression of LDHA and the hypoxia marker CAIX was associated with reduced relapse-free and overall survival. Hyperpolarized 13C-MRI represents a promising method for monitoring very early treatment response in breast cancer and has demonstrated prognostic potential.Significance:Hyperpolarized carbon-13 MRI allows response assessment in patients with breast cancer after 7–11 days of neoadjuvant chemotherapy and outperformed state-of-the-art and research quantitative proton MRI techniques.
Long-Term Prognostic Value of Stress Cardiovascular Magnetic Resonance–Related Coronary Revascularization to Predict Death: A Large Registry With >200 000 Patient-Years of Follow-Up
Authors: Pezel Théo , Unterseeh Thierry , Garot Philippe , Hovasse Thomas , Sanguineti Francesca , Toupin Solenn , Morisset Stéphane , Champagne Stéphane , Garot Jérôme 
Published: October 2021

Background:
Although the benefit of coronary revascularization in patients with stable coronary disease is debated, data assessing the potential interest of stress cardiovascular magnetic resonance (CMR) to guide coronary revascularization are limited. We aimed to assess the long-term prognostic value of stress CMR-related coronary revascularization in consecutive patients from a large registry.

Methods:
Between 2008 and 2018, a retrospective cohort study with a median follow-up of 6.0 years (interquartile range, 5.0–8.0) included all consecutive patients referred for stress CMR. CMR-related coronary revascularization was defined by any coronary revascularization performed within 90 days after CMR. The primary outcome was all-cause death based on the National Death Registry.

Results:

Among the 31 762 consecutive patients (mean age 63.7±12.1 years and 65.7% males), 2679 (8.4%) died at 206 453 patient-years of follow-up. Inducible ischemia and late gadolinium enhancement by CMR were associated with death (both
P
<0.001). In multivariable Cox regression, inducible ischemia and late gadolinium enhancement were independent predictors of death (hazard ratio, 1.61 [99.5% CI, 1.41–1.84]; hazard ratio, 1.62 [99.5% CI, 1.41–1.86], respectively;
P
<0.001). In the overall population, CMR-related coronary revascularization was an independent predictor of greater survival (hazard ratio, 0.58 [99.5% CI, 0.46–0.74];
P
<0.001). In 1680, 1:1 matched patients using a limited number of variables (840 revascularized, 840 nonrevascularized), CMR-related revascularization was associated with a lower incidence of death in patients with severe inducible ischemia (≥6 segments,
P
<0.001) but showed no benefit in patients with mild or moderate ischemia (<6 segments,
P
=0.109). Using multivariable analysis in the propensity-matched population, CMR-related revascularization remained an independent predictor of a lower incidence of all-cause mortality (hazard ratio, 0.66 [99.5% CI, 0.54–0.80],
P
<0.001).

Conclusions:
In this large observational series of consecutive patients, stress perfusion CMR had important incremental long-term prognostic value to predict death over traditional risk factors. CMR-related revascularization was associated with a lower incidence of death in patients with severe ischemia.
Triglyceride Levels and Residual Risk of Atherosclerotic Cardiovascular Disease Events and Death in Adults Receiving Statin Therapy for Primary or Secondary Prevention: Insights From the KP REACH Study
Authors: Ambrosy Andrew P. , Yang Jingrong , Sung Sue Hee , Allen Amanda R. , Fitzpatrick Jesse K. , Rana Jamal S. , Wagner Jeffrey , Philip Sephy , Abrahamson David , Granowitz Craig , Go Alan S. 
Published: October 2021

Background
Patients with risk factors or established atherosclerotic cardiovascular disease remain at high‐risk for ischemic events. Triglyceride levels may play a causal role.

Methods and Results
We performed a retrospective study of adults aged ≥45 years receiving statin therapy, with a low‐density lipoprotein cholesterol of 41 to 100 mg/dL, and ≥1 risk factor or established atherosclerotic cardiovascular disease between 2010 and 2017. Outcomes included death, all‐cause hospitalization, and major adverse cardiovascular events (myocardial infarction, stroke, or peripheral artery disease). The study sample included 373 389 primary prevention patients and 97 832 secondary prevention patients. The primary prevention cohort had a mean age of 65±10 years, with 51% women and 44% people of color, whereas the secondary prevention cohort had a mean age of 71±11 years, with 37% women and 32% people of color. Median triglyceride levels for the primary and secondary prevention cohorts were 122 mg/dL (interquartile range, 88–172 mg/dL) and 116 mg/dL (interquartile range, 84–164 mg/dL), respectively. In multivariable analyses, primary prevention patients with triglyceride levels ≥150 mg/dL were at lower adjusted risk of death (hazard ratio [HR], 0.91; 95% CI, 0.89–0.94) and higher risk of major adverse cardiovascular events (HR, 1.14; 95% CI, 1.05–1.24). In the secondary prevention cohort, patients with triglyceride levels ≥150 mg/dL were at lower adjusted risk of death (HR, 0.95; 95% CI, 0.92–0.97) and higher risk of all‐cause hospitalization (HR, 1.03; 95% CI, 1.01–1.05) and major adverse cardiovascular events (HR, 1.04; 95% CI, 1.05–1.24).

Conclusions
In a contemporary cohort receiving statin therapy, elevated triglyceride levels were associated with a greater risk of atherosclerotic cardiovascular disease events and lower risk of death.
Impact of Peripheral Microvascular Endothelial Dysfunction on White Matter Hyperintensity
Authors: Toya Takumi , Sara Jaskanwal D. , Scharf Eugene L. , Ahmad Ali , Nardi Valentina , Ozcan Ilke , Lerman Lilach O. , Lerman Amir 
Published: October 2021

Background
White matter hyperintensity (WMH), characterized by hyperintensities on T2‐weighted fluid‐attenuated inversion recovery brain magnetic resonance imaging, has been linked to an increased risk of ischemic stroke (IS). Endothelial dysfunction is an indicator of vascular dysfunction, predicting the risk of IS. This study aimed to investigate the association between endothelial dysfunction and regional WMH, and its impact on future risk of IS.

Methods and Results

We enrolled 219 patients (mean age, 53.1±14.1 years; 34.7% men) who underwent peripheral endothelial function assessment using reactive hyperemia peripheral arterial tonometry and brain magnetic resonance imaging without any history of IS. Volumetric WMH segmentation was automatically extrapolated using a validated automated digital tool. Total and juxtacortical WMH volume/intracranial volume (%) increased with aging and became more prominent in patients aged >50 years (n=131) than those aged ≤50 years (n=88) (total WMH: ≤50 years, Pearson
r
=0.24,
P
=0.03; >50 years, Pearson
r
=0.62,
P
<0.0001; juxtacortical WMH: ≤50 years, Pearson
r
=0.09,
P
=0.40; >50 years, Pearson
r
=0.55,
P
<0.0001). Reactive hyperemia peripheral arterial tonometry index was negatively associated with total and juxtacortical WMH volume/intracranial volume (%) in patients aged >50 years after adjustment for other covariates (reactive hyperemia peripheral arterial tonometry index, standardized β coefficient −0.17,
P
=0.04). Juxtacortical WMH volume/intracranial volume (%) was associated with an increased risk of IS during median follow‐up of 6.5 years (hazard ratio, 1.47; 95% CI, 1.05–1.92;
P
=0.03).

Conclusions
Peripheral endothelial dysfunction is associated with an increased volume of juxtacortical WMH in patients aged >50 years, which is a potential marker to predict future risk of IS.
Dual Antiplatelet Therapy Using Cilostazol in Patients With Stroke and Intracranial Arterial Stenosis
Authors: Uchiyama Shinichiro , Toyoda Kazunori , Omae Katsuhiro , Saita Ryotaro , Kimura Kazumi , Hoshino Haruhiko , Sakai Nobuyuki , Okada Yasushi , Tanaka Kortaro , Origasa Hideki , Naritomi Hiroaki , Houkin Kiyohiro , Yamaguchi Keiji , Isobe Masanori , Minematsu Kazuo , Matsumoto Masayasu , Tominaga Teiji , Tomimoto Hidekazu , Terayama Yasuo , Yasuda Satoshi , Yamaguchi Takenori 
Published: October 2021

Background
Long‐term benefit of dual antiplatelet therapy (DAPT) over single antiplatelet therapy (SAPT) for the prevention of recurrent stroke has not been established in patients with intracranial arterial stenosis. We compared the efficacy and safety of DAPT with cilostazol and clopidogrel or aspirin to those of SAPT with clopidogrel or aspirin in patients with intracranial arterial stenosis, who were recruited to the Cilostazol Stroke Prevention Study for Antiplatelet Combination trial, a randomized controlled trial in high‐risk Japanese patients with ischemic stroke.

Methods and Results
We compared the vascular and hemorrhagic events between DAPT and SAPT in patients with ischemic stroke and symptomatic or asymptomatic intracranial arterial stenosis of at least 50% in a major intracranial artery. Patients were placed in two groups: 275 were assigned to receive DAPT and 272 patients SAPT. The risks of ischemic stroke (hazard ratio [HR], 0.47; 95% CI, 0.23–0.95); and composite of stroke, myocardial infarction, and vascular death (HR, 0.48; 95% CI, 0.26–0.91) were lower in DAPT than SAPT, whereas the risk of severe or life‐threatening bleeding (HR, 0.72; 95% CI, 0.12–4.30) did not differ between the 2 treatment groups.

Conclusions
DAPT using cilostazol was superior to SAPT with clopidogrel or aspirin for the prevention of recurrent stroke and vascular events without increasing bleeding risk among patients with intracranial arterial stenosis after stroke.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01995370.
Association of ApoE Genotypes and Recovery From Intracerebral Hemorrhage in Very Low Birth Weight Infants
Authors: Humberg Alexander , Dzietko Mark , Schulz Sören , Felderhoff-Müser Ursula , Hüning Britta , Stein Anja , Fortmann Mats I. , Marissen Janina , Rausch Tanja K. , Herting Egbert , Härtel Christoph , Göpel Wolfgang ,   German Neonatal Network (GNN)
Published: October 2021

Background and Purpose:
Associations of APOE genotypes with intracerebral hemorrhage (ICH) in preterm infants were previously described. In adults, APOE-ε4 genotype has been proposed as susceptibility factor for impaired recovery after cerebral insult. We here aim to determine APOE genotype-specific neurological consequences of neonatal ICH at school age.

Methods:
In this multicenter observational cohort study, very low birth weight (<1500 g, <32 weeks gestational age) children were studied for cerebral palsy (CP) after ultrasound diagnosed ICH stratified by APOE genotype. Follow-up examination was done at the age of 5 to 6 years. Study personnel were blinded for perinatal information and complications. Participants were born between January 1, 2009 and December 31, 2013 and enrolled in the German Neonatal Network. Of 8022 infants primarily enrolled, 2467 children were invited for follow-up between January 1, 2014 and December 31, 2019. Univariate analyses and multivariate logistic regression models were used to assess the impact of APOE genotype (APOE-ε2, APOE-ε3, APOE-ε4) on CP after ICH.

Results:

Two thousand two hundred fifteen children participated at follow-up, including 363 children with ultrasound diagnosed neonatal ICH. In univariate analyses of children with a history of ICH, APOE-ε3 carriers had lower frequencies of CP (n=33/250; 13.2 [95% CI, 9.4%–17.8%]), as compared to APOE-ε2 (n=15/63; 23.8 [14.6%–35.3%],
P
=0.037) and –ε4 carriers (n=31/107; 29.0 [21.0%–38.0%],
P
<0.001), respectively. Regression models revealed an association of APOE-ε4 genotype and CP development (odds ratio, 2.77 [1.44–5.32],
P
=0.002) after ICH. Notably, at low-grade ICH (grade I) APOE-ε4 expression resulted in an increased rate of CP (n=6/39; 15.4 [6.7–29.0]) in comparison to APOE-ε3 (n=2/105; 1.9 [0.4%–6.0%],
P
=0.002).

Conclusions:
APOE-ε4 carriers have an increased risk for long-term motor deficits after ICH. We assume an effect even after low-grade neonatal ICH, but more data are needed to clarify this issue.
Treatment-Associated Stroke in Patients Undergoing Endovascular Therapy in the ARUBA Trial
Authors: Burks Joshua D. , Luther Evan M. , Govindarajan Vaidya , Chen Stephanie H. , Starke Robert M. 
Published: October 2021

Background and Purpose:
Since the publication of ARUBA trial (A Randomized Trial of Unruptured Brain Arteriovenous Malformations), outcomes in treated and untreated patients with unruptured arteriovenous malformation have been thoroughly compared. However, no prior analysis of ARUBA patients has sought to identify risk factors for perioperative stroke. Improved understanding of risks within the ARUBA cohort will help clinicians apply the study’s findings in a broader context.

Methods:
The National Institute of Neurological Disorders and Stroke database was queried for all data relating to ARUBA patients, including demographics, interventions undertaken, and timing of stroke. Retrospective cohort analysis was performed with the primary outcome of perioperative stroke in patients who underwent endovascular intervention, and stroke risk was modeled with multivariate analysis.

Results:

A total of 64 ARUBA patients were included in the analysis. One hundred and fifty-ninth interventions were performed, and 26 (16%) procedures resulted in stroke within 48 hours of treatment. Posterior cerebral artery supply (adjusted odds ratio, 4.42 [95% CI, 1.23–15.9],
P
=0.02) and Spetzler-Martin grades 2 and 3 arteriovenous malformation (adjusted odds ratio, 7.76 [95% CI, 1.20–50.3],
P
=0.03; 9.64 [95% CI, 1.36–68.4],
P
=0.04, respectively) were associated with increased perioperative stroke risk in patients who underwent endovascular intervention. Patients treated in the United States or Germany had a significantly lower stroke risk than patients treated in other countries (adjusted odds ratio, 0.18 [95% CI, 0.04–0.82],
P
=0.02).

Conclusions:
Knowing patient and lesion characteristics that increase risk during endovascular treatment can better guide clinicians managing unruptured brain arteriovenous malformation. Our analysis suggests risk of perioperative stroke is dependent on Spetzler-Martin grade and posterior-circulation arterial supply. Differences in regional treatment paradigms may also affect stroke risk.
Brain Network Dysfunction in Poststroke Delirium and Spatial Neglect: An fMRI Study
Authors: Boukrina Olga , Kowalczyk Mateusz , Koush Yury , Kong Yekyung , Barrett A.M. 
Published: October 2021

Background and Purpose:
Delirium, an acute reduction in cognitive functioning, hinders stroke recovery and contributes to cognitive decline. Right-hemisphere stroke is linked with higher delirium incidence, likely, due to the prevalence of spatial neglect (SN), a right-brain disorder of spatial processing. This study tested if symptoms of delirium and SN after right-hemisphere stroke are associated with abnormal function of the right-dominant neural networks specialized for maintaining attention, orientation, and arousal.

Methods:
Twenty-nine participants with right-hemisphere ischemic stroke undergoing acute rehabilitation completed delirium and SN assessments and functional neuroimaging scans. Whole-brain functional connectivity of 4 right-hemisphere seed regions in the cortical-subcortical arousal and attention networks was assessed for its relationship to validated SN and delirium severity measures.

Results:
Of 29 patients, 6 (21%) met the diagnostic criteria for delirium and 16 (55%) for SN. Decreased connectivity of the right basal forebrain to brain stem and basal ganglia predicted more severe SN. Increased connectivity of the arousal and attention network regions with the parietal, frontal, and temporal structures in the unaffected hemisphere was also found in more severe delirium and SN.

Conclusions:
Delirium and SN are associated with decreased arousal network activity and an imbalance of cortico-subcortical hemispheric connectivity. Better understanding of neural correlates of poststroke delirium and SN will lead to improved neuroscience-based treatment development for these disorders.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03349411.