bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel selection paradigms for endovascular stroke treatment in the extended time window
Authors: Bouslama Mehdi , Haussen Diogo C , Rodrigues Gabriel , Barreira Clara , Frankel Michael , Nogueira Raul G 
Published: June 2021

Background and purposeThe optimal selection methodology for stroke thrombectomy beyond 6 hours remains to be established.MethodsReview of a prospectively collected database of thrombectomy patients with anterior circulation strokes, adequate CT perfusion (CTP) maps, National Institute of Health Stroke Scale (NIHSS)≥10 and presenting beyond 6 hours from January 2014 to October 2018. Patients were categorised according to five selection paradigms: DAWN clinical-core mismatch (DAWN-CCM): between age-adjusted NIHSS and CTP core, DEFUSE 3 perfusion imaging mismatch (DEFUSE-3-PIM): between CTP-derived perfusion defect (Tmax >6 s lesion) and ischaemic core volumes and three non-contrast CT Alberta Stroke Program Early CT Score (ASPECTS)-based criteria: age-adjusted clinical-ASPECTS mismatch (aCAM): between age-adjusted NIHSS and ASPECTS, eloquence-adjusted clinical ASPECTS mismatch (eCAM): ASPECTS 6–10 and non-involvement of the right M6 and left M4 areas and standard clinical ASPECTS mismatch (sCAM): ASPECTS 6–10.Results310 patients underwent analysis. DEFUSE-3-PIM had the highest proportion of qualifying patients followed by sCAM, eCAM, aCAM and DAWN-CCM (93.5%, 92.6%, 90.6%, 90% and 84.5%, respectively). Patients meeting aCAM, eCAM, sCAM and DAWN-CCM criteria had higher rates of 90-day good outcome compared with their non-qualifying counterparts(43.2% vs 12%,p=0.002; 42.4% vs 17.4%, p=0.02; 42.4% vs 11.2%, p=0.009; and 43.7% vs 20.5%, p=0.007, respectively). There was no difference between patients meeting DEFUSE-3-PIM criteria versus not(40.8% vs 31.3%,p=0.45). In multivariate analysis, all selection modalities except for DEFUSE-3-PIM were independently associated with 90-day good outcome.ConclusionsASPECTS-based selection paradigms for late presenting and wake-up strokes ET have comparable proportions of qualifying patients and similar 90-day functional outcomes as DAWN-CCM and DEFUSE-3-PIM. They also might lead to better outcome discrimination. These could represent a potential alternative for centres where access to advanced imaging is limited.
Making smoking history: temporal changes in support for a future smoking ban and increasing taxes in the general population of Denmark
Authors: Toxværd Cecilie Goltermann , Pisinger Charlotta , Lykke Maja Bülow , Lau Cathrine Juel 
Published: June 2021

BackgroundAn end date for smoking has been adopted in several countries and is now being discussed by governments all over the world. However, little is known about temporal changes in citizens’ support for a future smoking ban.AimTo examine temporal changes in support for a future smoking ban and for increasing taxes on tobacco in Denmark, and to explore whether these changes differ across sex, age, educational attainment, smoking status and between smokers with/without intention to quit.MethodThe study was based on two waves of ‘The Danish Capital Region Health Survey’ conducted in 2013 and 2017. The pooled study sample included 96 521 citizens aged ≥16 years old.ResultsPublic support for a future smoking ban increased from 30.6% in 2013 to 50.3% in 2017, whereas support for increasing tobacco taxes remained unchanged at 59%. Support for a future smoking ban increased significantly in almost all subgroups from 2013 to 2017: Support among daily smokers increased by 27% between 2013 and 2017. Support among never smokers was almost 2.63 times higher than among smokers in 2013 and increased further in 2017 (OR: 2013=2.63; 2017=5.13).ConclusionThis study indicates a readiness to support a future smoking ban and increasing tobacco taxes. Support for a future smoking ban has increased from 2013 to 2017 among both young people and adults. By 2017, about half of the population supported a future smoking ban and increasing tobacco taxes. Findings may help inform policy-making related to endgame strategies.
Optimal quantum tomography with constrained measurements arising from unitary bases
Authors: Chaturvedi S. , Ghosh S. , Parthasarathy K. R. , Singh Ajit Iqbal 
Published: June 2021

The purpose of this paper is to introduce techniques of obtaining optimal ways to determine a [Formula: see text]-level quantum state or distinguish such states. It entails designing constrained elementary measurements extracted from maximal abelian subsets of a unitary basis [Formula: see text] for the operator algebra [Formula: see text] of a Hilbert space [Formula: see text] of finite dimension [Formula: see text] or, after choosing an orthonormal basis for [Formula: see text], for the ⋆-algebra [Formula: see text] of complex matrices of order [Formula: see text]. Illustrations are given for the techniques. It is shown that the Schwinger basis [Formula: see text] of unitary operators can give for [Formula: see text], a product of primes [Formula: see text] and [Formula: see text], the ideal number [Formula: see text] of rank one projectors that have a few quantum mechanical overlaps (or, for that matter, a few angles between the corresponding unit vectors). Finally, we give a combination of the tensor product and constrained elementary measurement techniques to deal with all [Formula: see text], though with more overlaps or angles depending on the factorization of [Formula: see text] as a product of primes or their powers like [Formula: see text] with [Formula: see text], all primes, [Formula: see text] for [Formula: see text], or other types. A comparison is drawn for different forms of unitary bases for the Hilbert space factors of the tensor product like [Formula: see text] or [Formula: see text], where [Formula: see text] is the Galois field of size [Formula: see text] and [Formula: see text] is the ring of integers modulo [Formula: see text]. Even though as Hilbert spaces they are isomorphic, but quantum mechanical system-wise, these tensor products are different.In the process, we also study the equivalence relation on unitary bases defined by R. F. Werner [J. Phys. A: Math. Gen. 34 (2001) 7081–7094], connect it to local operations on maximally entangled vectors bases, find an invariant for equivalence classes in terms of certain commuting systems, called fan representations, and, relate it to mutually unbiased bases and Hadamard matrices. Illustrations are given in the context of Latin squares and projective representations as well.
Targeting Glucose Metabolism Sensitizes Pancreatic Cancer to MEK Inhibition
Authors: Yan Liang , Tu Bo , Yao Jun , Gong Jing , Carugo Alessandro , Bristow Christopher A. , Wang Qiuyun , Zhu Cihui , Dai Bingbing , Kang Ya'an , Han Leng , Feng Ningping , Jin Yanqing , Fleming Jason , Heffernan Timothy P. , Yao Wantong , Ying Haoqiang 
Published: June 2021

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is almost universally lethal. A critical unmet need exists to explore essential susceptibilities in PDAC and to identify druggable targets to improve PDAC treatment. KRAS mutations dominate the genetic landscape of PDAC and lead to activation of multiple downstream pathways and cellular processes. Here, we investigated the requirement of these pathways for tumor maintenance using an inducible KrasG12D-driven PDAC mouse model (iKras model), identifying that RAF-MEK-MAPK signaling is the major effector for oncogenic KRAS-mediated tumor maintenance. However, consistent with previous studies, MEK inhibition had minimal therapeutic effect as a single agent for PDAC in vitro and in vivo. Although MEK inhibition partially downregulated transcription of glycolysis genes, it failed to suppress glycolytic flux in PDAC cells, which is a major metabolic effector of oncogenic KRAS. Accordingly, an in vivo genetic screen identified multiple glycolysis genes as potential targets that may sensitize tumor cells to MEK inhibition. Inhibition of glucose metabolism with low-dose 2-deoxyglucose in combination with a MEK inhibitor induced apoptosis in KrasG12D-driven PDAC cells in vitro. The combination also inhibited xenograft PDAC tumor growth and prolonged overall survival in a genetically engineered PDAC mouse model. Molecular and metabolic analyses indicated that co-targeting glycolysis and MAPK signaling results in apoptosis via induction of lethal endoplasmic reticulum stress. Together, our work suggests that combined inhibition of glycolysis and the MAPK pathway may serve as an effective approach to target KRAS-driven PDAC.

Significance:
This study demonstrates the critical role of glucose metabolism in resistance to MAPK inhibition in KRAS-driven pancreatic cancer, uncovering a potential therapeutic approach for treating this aggressive disease.
Identification of a Novel Inflamed Tumor Microenvironment Signature as a Predictive Biomarker of Bacillus Calmette-Guérin Immunotherapy in Non–Muscle-Invasive Bladder Cancer
Authors: Damrauer Jeffrey S. , Roell Kyle R. , Smith Markia A. , Sun Xuezheng , Kirk Erin L. , Hoadley Katherine A. , Benefield Halei C. , Iyer Gopakumar , Solit David B. , Milowsky Matthew I. , Kim William Y. , Nielsen Matthew E. , Wobker Sara E. , Dalbagni Guido , Al-Ahmadie Hikmat A. , Olshan Andrew F. , Bochner Bernard H. , Furberg Helena , Troester Melissa A. , Pietzak Eugene J. 
Published: June 2021

Abstract

Purpose:
Improved risk stratification and predictive biomarkers of treatment response are needed for non–muscle-invasive bladder cancer (NMIBC). Here we assessed the clinical utility of targeted RNA and DNA molecular profiling in NMIBC.

Experimental Design:
Gene expression in NMIBC samples was profiled by NanoString nCounter, an RNA quantification platform, from two independent cohorts (n = 28, n = 50); targeted panel sequencing was performed in a subgroup (n = 50). Gene signatures were externally validated using two RNA sequencing datasets of NMIBC tumors (n = 438, n = 73). Established molecular subtype classifiers and novel gene expression signatures were assessed for associations with clinicopathologic characteristics, somatic tumor mutations, and treatment outcomes.

Results:
Molecular subtypes distinguished between low-grade Ta tumors with FGFR3 mutations and overexpression (UROMOL-class 1) and tumors with more aggressive clinicopathologic characteristics (UROMOL-classes 2 and 3), which were significantly enriched with TERT promoter mutations. However, UROMOL subclasses were not associated with recurrence after bacillus Calmette-Guérin (BCG) immunotherapy in two independent cohorts. In contrast, a novel expression signature of an inflamed tumor microenvironment (TME) was associated with improved recurrence-free survival after BCG. Expression of immune checkpoint genes (PD-L1/PD-1/CTLA-4) was associated with an inflamed TME, but not with higher recurrence rates after BCG. FGFR3 mutations and overexpression were both associated with low immune signatures.

Conclusions:
Assessment of the immune TME, rather than molecular subtypes, is a promising predictive biomarker of BCG response. Modulating the TME in an immunologically “cold” tumor warrants further investigation. Integrated transcriptomic and exome sequencing should improve treatment selection in NMIBC.
Activation of Autophagic Flux Blunts Cardiac Ischemia/Reperfusion Injury
Authors: Xie Min , Cho Geoffrey W. , Kong Yongli , Li Dan L. , Altamirano Francisco , Luo Xiang , Morales Cyndi R. , Jiang Nan , Schiattarella Gabriele G. , May Herman I. , Medina Jessica , Shelton John M. , Ferdous Anwarul , Gillette Thomas G. , Hill Joseph A. 
Published: June 2021

Rationale:
Reperfusion injury accounts for up to half of myocardial infarct size, and meaningful clinical therapies targeting it do not exist. We have reported previously that autophagy is reduced during reperfusion and that HDAC (histone deacetylase) inhibition enhances cardiomyocyte autophagy and blunts ischemia/reperfusion (I/R) injury when administered at the time of reperfusion. However, whether inducing autophagy per se, as opposed to other effects triggered by HDAC inhibition, is sufficient to protect against reperfusion injury is not clear.

Objective:
We set out to test whether augmentation of autophagy using a specific autophagy-inducing peptide, TB (Tat-Beclin), protects the myocardium through reduction of reactive oxygen species (ROS) during reperfusion injury.

Methods and Results:
Eight- to 12-week-old, WT (wild type) C57BL6 mice and tamoxifen-inducible cardiomyocyte-specific ATG7 KO (ATG7 knockout) mice (to test the dependency on autophagy) were randomized into 2 groups: exposed to a control TS (Tat-scrambled) peptide or a TB peptide. Each group was subjected to I/R surgery (45-minute coronary ligation, 24-hour reperfusion). Infarct size, systolic function, autophagic flux, and ROS were assayed. Cultured neonatal rat ventricular myocytes were exposed to TB during simulated I/R injury. ATG7 knockdown by small interfering RNA in neonatal rat ventricular myocytes was used to evaluate the role of autophagy. TB treatment at reperfusion reduced infarct size by 20% (absolute reduction; 50% relative reduction) and improved contractile function. Improvement correlated with increased autophagic flux in the border zone with less oxidative stress. ATG7 KO mice did not manifest TB-promoted cardioprotection during I/R. In neonatal rat ventricular myocytes subjected to I/R, TB reduced cell death by 41% and reduced I/R-induced ROS generation. Conversely, ATG7 knockdown in neonatal rat ventricular myocytes abolished these beneficial effects of TB on cell death and ROS reduction.

Conclusions:
Induction of autophagy at the time of reperfusion is sufficient to mitigate myocardial reperfusion injury by reducing ROS and cell death. Maintenance of appropriate autophagic flux may emerge as a viable clinical therapy to reduce reperfusion injury in acute myocardial infarction.
Impaired Binding to Junctophilin-2 and Nanostructural Alteration in CPVT Mutation
Authors: Yin Liheng , Zahradnikova Alexandra , Rizzetto Riccardo , Boncompagni Simona , Rabesahala de Meritens Camille , Zhang Yadan , Joanne Pierre , Marqués-Sulé Elena , Aguilar-Sánchez Yuriana , Fernández-Tenorio Miguel , Villejoubert Olivier , Li Linwei , Wang Yue Yi , Mateo Philippe , Nicolas Valérie , Gerbaud Pascale , Lai F. Anthony , Perrier Romain , Álvarez Julio L. , Niggli Ernst , Valdivia Héctor H. , Valdivia Carmen R. , Ramos-Franco Josefina , Zorio Esther , Zissimopoulos Spyros , Protasi Feliciano , Benitah Jean-Pierre , Gómez Ana M. 
Published: June 2021

Rationale:

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare disease, manifested by syncope or sudden death in children or young adults under stress conditions. Mutations in the Ca
2+
release channel/RyR2 (type 2 ryanodine receptor) gene account for about 60% of the identified mutations. Recently, we found and described a mutation in RyR2 N-terminal domain, RyR2
R420Q
.

Objective:
To determine the arrhythmogenic mechanisms of this mutation.

Methods and Results:

Ventricular tachycardias under stress conditions were observed in both patients with catecholaminergic polymorphic ventricular tachycardia and knock-in mice. During action potential recording (by patch-clamp in knock-in mouse cardiomyocytes and by microelectrodes in mutant human induced pluripotent stem cell-derived cardiomyocytes), we observed an increased occurrence of delayed afterdepolarizations under isoproterenol stimulation, associated with increased Ca
2+
waves during confocal Ca
2+
recording in both mouse and human RyR2
R420Q
cardiomyocytes. In addition, Ca
2+
-induced Ca
2+
-release, as well as a rough indicator of fractional Ca
2+
release, were higher and Ca
2+
sparks longer in the RyR2
R420Q
-expressing cells. At the ultrastructural nanodomain level, we observed smaller RyR2 clusters and widened junctional sarcoplasmic reticulum measured by gated stimulated emission depletion super-resolution and electron microscopy, respectively. The increase in junctional sarcoplasmic reticulum width might be due to the impairment of RyR2
R420Q
binding to JPH2 (junctophilin-2), as there were less junctophilin-2 coimmunoprecipitated with RyR2
R420Q
. At the single current level, the RyR2
R420Q
channel dwells longer in the open state at low intracellular Ca
2+
([Ca
2+
]
i
), but there is predominance of a subconductance state. The latter might be correlated with an enhanced interaction between the N terminus and the core solenoid, a RyR2 interdomain association that has not been previously implicated in the pathogenesis of arrhythmias and sudden cardiac death.

Conclusions:

The RyR2
R420Q
catecholaminergic polymorphic ventricular tachycardia mutation modifies the interdomain interaction of the channel and weakens its association with JPH2. These defects may underlie both nanoscale disarrangement of the dyad and channel dysfunction.
Cervical Endocrine Surgery With a Novel Opioid-Limited Perioperative Protocol
Authors: Boudiab Elizabeth M. , Lapkus Morta , Reilly Jordan , Studzinski Diane , Czako Peter , Asbahi Moumen , Schostak Michael , Schmidt Carol , Nagar Sapna 
Published: June 2021

Background Recent studies have demonstrated that patients undergoing cervical endocrine surgery could be comfortably discharged with minimal opioid analgesia. However, no study to date has examined the efficacy of limiting administration of opioids intraoperatively. We have developed a novel protocol for patients undergoing cervical endocrine surgery that eliminates perioperative opioids. We sought to determine the efficacy of this protocol and its impact on opioid use at discharge. Methods We conducted a prospective opt-in opioid-limited surgery program study to opioid-naive patients scheduled for cervical endocrine surgery beginning in August 2019. Postoperatively, nonopioid analgesia was encouraged, but patients were also given a low dose prescription for opioids at discharge. Patients were then matched with 2 retrospective control groups, patients from 2014-2016 and 2017-2018, in order to account for increased public awareness of opioid-prescribing patterns. Primary end points included perioperative opioid use. Secondary end points included postoperative pain scores and complications. Results 218 patients underwent cervical endocrine surgery with our opioid-limited protocol between August 2019 and February 2020. Nine patients received opioids intraoperatively (4%) and 109 (50%) filled their opioid prescriptions at discharge. Compared to retrospective control groups, the average oral morphine equivalents (OME) administered intraoperatively and prescribed postoperatively were significantly lower ( P < .0001). Pain scores and complication rates were similar in all groups ( P = .7247). Discussion Our novel opioid-limited surgery protocol used in conjunction with preoperative counseling is an effective approach for pain control in patients undergoing cervical endocrine surgery and limits opioid exposure throughout the perioperative period.
The New Political Economy of the Twenty-First-Century Higher Education
Authors: Bhushan Sudhanshu 
Published: June 2021

I pose the problems of quality in higher education to be addressed through a bureaucratic, technology-centric and accountability-based framework. It relies heavily on quantitative, information-based and ideal institutional system of higher education. The new political economy of the twenty-first-century higher education creates the balance of power in favour of state and utilises the individual choice and market-based principle of governance. The article argues the alternative in terms of shifting the power in favour of academia. The power of academia shall be realised only if the attention is focussed both on creation as well as the purpose of knowledge in the twenty-first century. Universities need to be hermeneutic for allowing the scope of creative activity and accommodate the voices of marginalised sections. It means practical rationality should guide the academia and administrators of higher education. JEL Code: I2, I28
The Relational Dynamics of Becoming Popular Feminist Subjects: The World March of Women and Rural/Peasant Women’s Organizing in Brazil in the 2000s
Authors: Masson Dominique , Beaulieu Bastien Elsa 
Published: June 2021

The constitution and consolidation of rural and peasant women as popular feminist subjects in Brazil are the result not only of processes internal to these constituencies but also of relational dynamics involving cross-class and cross-movement popular activist organizations. Since the end of the 1990s, organizations and activists identifying with the World March of Women in western Rio Grande do Norte and at the national scale have consciously engaged with rural and peasant women and assisted them in becoming and consolidating themselves as popular feminist subjects. Relational dynamics have also been important in the (unfinished) process of transforming, extending, and deepening the dual meaning of “popular feminism” in Brazil. A constituição e consolidação das mulheres rurais e camponesas como sujeitos feministas populares no Brasil são o resultado não apenas de processos internos desses grupos, mas também das dinâmicas relacionais que envolvem organizações ativistas populares de classes e movimentos. Desde o final da década de 1990, organizações e ativistas que se identificam com a Marcha Mundial das Mulheres da região Oeste do Rio Grande do Norte e em escala nacional têm se engajado conscientemente com as mulheres rurais e camponesas, ajudando as mesmas a se tornarem e consolidarem como sujeitos feministas populares. As dinâmicas relacionais têm sido importantes também no processo (incompleto) de transformação, extensão e aprofundamento do duplo significado de “feminismo popular” no Brasil.
The Diagnostic Yield of Excisional Biopsy in Cervical Lymphadenopathy: A Retrospective Analysis of 158 Biopsies in Adults
Authors: Bassiouni Mohamed , Kang Gyeongphill , Olze Heidi , Dommerich Steffen , Arens Philipp 
Published: June 2021

Objectives: Cervical lymph nodes are the most common site of peripheral lymphadenopathy. The underlying etiologies are usually benign and self-limiting but may include malignancies or other severe life-threatening diseases. The aim of the current study was to investigate the various underlying pathologies of cervical lymphadenopathy as assessed by the diagnostic yield of excisional lymph node biopsies of the neck in a tertiary adult practice. The evaluation was performed in light of previous literature and regional epidemiological patterns. Methods: Retrospective analysis of hospital charts of 158 adult patients who underwent an excisional biopsy for suspected cervical lymphadenopathy at a tertiary referral head and neck service between January 2017 and December 2019. Results: The most common underlying pathology was unspecific and/or reactive lymphadenitis in 44.5% of specimens, followed by malignant disease in 38.6% of cases. An age above 40 years was significantly correlated with an increased likelihood of malignant disease. Lower jugular and posterior triangle lymph nodes showed higher malignancy rates than other groups (100% and 66.7%, respectively). The overall surgical complication rate was 2.5%. Conclusions: The results of the current study serve as an indicator of the variety of etiologies causing cervical lymphadenopathy. In particular, given the increasing incidence of malignant diseases in recent decades, the findings should alert physicians to the importance of lymph node biopsy for excluding malignancy in persistent cervical lymphadenopathy especially in older adults. The findings emphasize the value of excisional lymph node biopsy of the neck as a useful diagnostic tool in adult patients with peripheral lymphadenopathy.