bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibody-based redirection of universal Fabrack-CAR T cells selectively kill antigen bearing tumor cells
Authors: Kuo Yi-Chiu , Kuo Cheng-Fu , Jenkins Kurt , Hung Alfur Fu-Hsin , Chang Wen-Chung , Park Miso , Aguilar Brenda , Starr Renate , Hibbard Jonathan , Brown Christine , Williams John C 
Published: June 2022

BackgroundChimeric antigen receptor (CAR) T cells engineered to recognize and target tumor associated antigens have made a profound impact on the quality of life for many patients with cancer. However, tumor heterogeneity and intratumoral immune suppression reduce the efficacy of this approach, allowing for tumor cells devoid of the target antigen to seed disease recurrence. Here, we address the complexity of tumor heterogeneity by developing a universal CAR.MethodWe constructed a universal Fabrack-CAR with an extracellular domain composed of the non-tumor targeted, cyclic, twelve residue meditope peptide that binds specifically to an engineered binding pocket within the Fab arm of monoclonal antibodies (mAbs). As this site is readily grafted onto therapeutic mAbs, the antigen specificity of these universal Fabrack-CAR T cells is simply conferred by administering mAbs with specificity to the heterogeneous tumor.ResultsUsing in vitro and in vivo studies with multiple meditope-engineered mAbs, we show the feasibility, specificity, and robustness of this approach. These studies demonstrate antigen- and antibody-specific T cell activation, proliferation, and IFNγ production, selective killing of target cells in a mixed population, and tumor regression in animal models.ConclusionCollectively, these findings support the feasibility of this universal Fabrack-CAR T cell approach and provide the rationale for future clinical use in cancer immunotherapy.
Randomized comparison between perineural dexamethasone and combined perineural dexamethasone-dexmedetomidine for ultrasound-guided infraclavicular block
Authors: Aliste Julián , Layera Sebastián , Bravo Daniela , Aguilera Germán , Erpel Hans , García Armando , Lizama Marcelo , Finlayson Roderick J , Tran De Q 
Published: June 2022

BackgroundThis randomized trial compared perineural dexamethasone with combined perineural dexamethasone-dexmedetomidine for ultrasound-guided infraclavicular block. We hypothesized that the combination of perineural adjuvants would result in a longer motor block.MethodsFifty patients undergoing upper limb surgery with ultrasound-guided infraclavicular block (using 35 mL of lidocaine 1%-bupivacaine 0.25% with epinephrine 5 µg/mL) were randomly allocated to receive perineural dexamethasone (2 mg) or combined perineural dexamethasone (2 mg)-dexmedetomidine (50 µg). After the performance of the block, a blinded observer assessed the success rate (defined as a minimal sensorimotor composite score of 14 out of 16 points at 30 min), the onset time (defined as the time required to reach a minimal composite score of 14 points) as well as the incidence of surgical anesthesia (defined as the ability to complete surgery without local infiltration, supplemental blocks, intravenous opioids or general anesthesia).Postoperatively, the blinded observer contacted patients with successful blocks to inquire about the duration of motor block, sensory block and postoperative analgesia.ResultsNo intergroup differences were observed in terms of success rate, onset time and surgical anesthesia. Compared with dexamethasone alone, combined dexamethasone-dexmedetomidine provided longer durations of motor block (21.5 (2.7) vs 17.0 (3.9) hours; p<0.001; 95% CI 2.6 to 6.4), sensory block (21.6 (3.6) vs 17.2 (3.6) hours; p<0.001; 95% CI 2.2 to 6.5), and postoperative analgesia (25.5 (9.4) vs 23.5 (5.6) hours; p=0.038; 95% CI 1.0 to 7.7).ConclusionCompared with perineural dexamethasone (2 mg) alone, combined perineural dexamethasone (2 mg)-dexmedetomidine (50 µg) results in longer durations of sensorimotor block and analgesia. Further studies are required to determine the optimal dosing combination for dexamethasone-dexmedetomidine.Trial registration numberClinicalTrials.gov identifier:NCT04875039.
Massive gauge particles versus Goldstone bosons in non-Hermitian non-Abelian gauge theory
Authors: Fring Andreas , Taira Takano 
Published: June 2022

AbstractWe investigate the Englert–Brout–Higgs–Guralnik–Hagen–Kibble mechanism for non-Hermitian field theories with local non-Abelian gauge symmetry in different regions of their parameter spaces. We demonstrate that the two aspects of the mechanism, that is giving mass to gauge vector bosons and at the same time preventing the existence of massless Goldstone bosons, remain to be synchronized in all regimes characterized by a modified CPT symmetry. In the domain of parameter space where the “would be Goldstone bosons” can be identified the gauge vector bosons become massive and the Goldstone bosons cease to exist. The mechanism is also in tact at the standard exceptional points. However, at the zero exceptional points, that is when the eigenvalues of the mass squared matrix vanish irrespective of the symmetry breaking, the mechanism breaks down as the Goldstone bosons cannot be identified and the gauge vector bosons remain massless. This breakdown coincides with the vanishing of the CPT inner product of symmetry breaking vacua defined on the eigenvector space of mass squared matrix. We verify this behaviour for a theory with SU(2) symmetry in which the complex scalar fields are taken in the fundamental as well as in the adjoint representation.
On random matrices arising in deep neural networks: General I.I.D. case
Authors: Pastur Leonid , Slavin Victor 
Published: June 2022

We study the eigenvalue distribution of random matrices pertinent to the analysis of deep neural networks. The matrices resemble the product of the sample covariance matrices, however, an important difference is that the analog of the population covariance matrix is now a function of random data matrices (synaptic weight matrices in the deep neural network terminology). The problem has been treated in recent work [J. Pennington, S. Schoenholz and S. Ganguli, The emergence of spectral universality in deep networks, Proc. Mach. Learn. Res. 84 (2018) 1924–1932, arXiv:1802.09979] by using the techniques of free probability theory. Since, however, free probability theory deals with population covariance matrices which are independent of the data matrices, its applicability in this case has to be justified. The justification has been given in [L. Pastur, On random matrices arising in deep neural networks: Gaussian case, Pure Appl. Funct. Anal. (2020), in press, arXiv:2001.06188] for Gaussian data matrices with independent entries, a standard analytical model of free probability, by using a version of the techniques of random matrix theory. In this paper, we use another version of the techniques to extend the results of [L. Pastur, On random matrices arising in deep neural networks: Gaussian case, Pure Appl. Funct. Anal. (2020), in press, arXiv:2001.06188] to the case where the entries of the data matrices are just independent identically distributed random variables with zero mean and finite fourth moment. This, in particular, justifies the mean field approximation in the infinite width limit for the deep untrained neural networks and the property of the macroscopic universality of random matrix theory in this case.
The dynamics of remembering and forgetting
Authors: Baquero Carlos , Cabecinhas Rosa 
Published: June 2022

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http://cacm.acm.org/blogs/blog-cacm
Carlos Baquero and Rosa Cabecinhas consider how we make assumptions about authors' roles and relative contributions when reading papers.
KDM5A Inhibits Antitumor Immune Responses Through Downregulation of the Antigen-Presentation Pathway in Ovarian Cancer
Authors: Liu Heng , Lin Jianhuang , Zhou Wei , Moses Renyta , Dai Zhongping , Kossenkov Andrew V. , Drapkin Ronny , Bitler Benjamin G. , Karakashev Sergey , Zhang Rugang 
Published: June 2022

Abstract

The extent to which effector CD8+ T cells infiltrate into tumors is one of the major predictors of clinical outcome for patients with epithelial ovarian cancer (EOC). Immune cell infiltration into EOC is a complex process that could be affected by the epigenetic makeup of the tumor. Here, we have demonstrated that a lysine 4 histone H3 (H3K4) demethylase, (lysine-specific demethylase 5A; KDM5A) impairs EOC infiltration by immune cells and inhibits antitumor immune responses. Mechanistically, we found that KDM5A silenced genes involved in the antigen processing and presentation pathway. KDM5A inhibition restored the expression of genes involved in the antigen-presentation pathway in vitro and promoted antitumor immune responses mediated by CD8+ T cells in vivo in a syngeneic EOC mouse model. A negative correlation between expression of KDM5A and genes involved in the antigen processing and presentation pathway such as HLA-A and HLA-B was observed in the majority of cancer types. In summary, our results establish KDM5A as a regulator of CD8+ T-cell infiltration of tumors and demonstrate that KDM5A inhibition may provide a novel therapeutic strategy to boost antitumor immune responses.
Estrogen Protects Cardiac Function and Energy Metabolism in Dilated Cardiomyopathy Induced by Loss of Cardiac IRS1 and IRS2
Authors: Yan Hui , Yang Wanbao , Zhou Fenghua , Pan Quan , Allred Kimberly , Allred Clinton , Sun Yuxiang , Threadgill David , Dostal David , Tong Carl , Guo Shaodong 
Published: June 2022

Background:
Type 2 diabetes (T2D) is a high-risk factor for incident of cardiovascular diseases. Women at young ages show a reduced incidence of both T2D and cardiovascular diseases compared with men, but these disparities disappear in postmenopausal women versus age-matched men. Thus, ovaries and ovarian hormones, such as estrogen, are expected to protect from T2D and cardiovascular diseases. In this study, we aimed to investigate the role of ovaries and ovarian hormone estrogen in cardiac function and energy metabolism using the cardiac IRS (insulin receptor substrate) 1 and IRS2 double genes knockout mice that mimic cardiac insulin resistance.

Methods:

Control and heart-specific IRS1/2 double genes knockout mice were treated with placebo or 17β-estradiol (E
2
) pellets, respectively, through subcutaneous implantation. Female mice were subjected to a bilateral ovariectomy surgery to remove endogenous E
2
. The cardiac function and energy metabolism were determined using echocardiography and indirect calorimeter, respectively.

Results:

All male heart-specific IRS1/2 double genes knockout mice died of heart failure at 6 to 8 weeks as we previously described (Qi et al), but all female heart-specific IRS1/2 double genes knockout mice survived >1 year. Removal of ovaries in heart-specific IRS1/2 double genes knockout female mice resulted in cardiac dysfunction, and ultimately animal death. However, E
2
supplementation prevented the dilated cardiomyopathy, improved cardiac function and energy metabolism, and enhanced lifespan in both male and ovariectomy female mice deficient for cardiac IRS1 and IRS2 genes, largely owing to the activation of Akt (protein kinase B)-Foxo1 (O1 class of forkhead/winged helix transcription factor) signaling cascades.

Conclusions:
These results show that estrogen protects mice from cardiac insulin resistance-induced diabetic cardiomyopathy. This may provide a fundamental mechanism for the gender difference for the incidence of both T2D and cardiovascular diseases. This study highlights that estrogen signaling could be a potential target for improving cardiac function and energy metabolism in humans with T2D.
Visual Coronary and Aortic Calcium Scoring on Chest Computed Tomography Predict Mortality in Patients With Low-Density Lipoprotein-Cholesterol ≥190 mg/dL
Authors: Castagna Francesco , Miles Jeremy , Arce Javier , Leiderman Ephraim , Neshiwat Patrick , Ippolito Paul , Friedmann Patricia , Schenone Aldo , Zhang Lili , Rodriguez Carlos J. , Blaha Michael J. , Levsky Jeffrey M. , Garcia Mario J , Slipczuk Leandro 
Published: June 2022

Background:
Current guidelines recommend coronary artery calcium (CAC) scoring for stratification of atherosclerotic cardiovascular disease risk only in patients with borderline to intermediate risk score by the pooled cohort equation with low-density lipoprotein-cholesterol (LDL-C) of 70 to 190 mg/dL. It remains unknown if CAC or thoracic aorta calcification (TAC), detected on routine chest computed tomography, can provide further risk stratification in patients with LDL-C≥190 mg/dL.

Methods:
From a multisite medical center, we retrospectively identified all patients from March 2005 to June 2021 age ≥40 years, without established atherosclerotic cardiovascular disease and LDL-C≥190 mg/dL who had non-gated non-contrast chest computed tomography within 3 years of LDL-C measurement. Ordinal CAC and TAC scores were measured by visual inspection. Kaplan-Meier curves and multivariable Cox-regression models were built to ascertain the association of CAC and TAC scores with all-cause mortality.

Results:
We included 811 patients with median age 59 (53–68) years, 262 (32.3%) were male, and LDL-C median level was 203 (194–217) mg/dL. Patients were followed for 6.2 (3.29–9.81) years, and 109 (13.4%) died. Overall, 376 (46.4%) of patients had CAC=0 and 226 (27.9%) had TAC=0. All-cause mortality increased with any CAC and moderate to severe TAC. In a multivariate model, patients with CAC had a significantly higher mortality compared with those without CAC: mild hazard ratio (HR), 1.71 (1.03–2.83), moderate HR, 2.12 (1.14–3.94), and severe HR, 3.49 (1.94–6.27). Patients with moderate TAC (HR, 2.34 [1.19–4.59]) and those with severe TAC (HR, 3.02 [1.36–6.74]) had higher mortality than those without TAC.

Conclusions:
In patients without history of atherosclerotic cardiovascular disease and LDL-C≥190 mg/dL, the presence and severity of CAC and TAC are independently associated with all-cause mortality.
Differential Impact of Coronary Revascularization on Long-Term Clinical Outcome According to Coronary Flow Characteristics: Analysis of the International ILIAS Registry
Authors: Hamaya Rikuta , van de Hoef Tim P. , Lee Joo Myung , Hoshino Masahiro , Kanaji Yoshihisa , Murai Tadashi , Boerhout Coen K.M. , de Waard Guus A. , Jung Ji-Hyun , Lee Seung Hun , Mejia Renteria Hernan , Echavarria-Pinto Mauro , Meuwissen Martijn , Matsuo Hitoshi , Madera-Cambero Maribel , Eftekhari Ashkan , Effat Mohamed A. , Marques Koen , Doh Joon-Hyung , Christiansen Evald H. , Banerjee Rupak , Nam Chang-Wook , Niccoli Giampaolo , Nakayama Masafumi , Tanaka Nobuhiro , Shin Eun-Seok , Sasano Tetsuo , Chamuleau Steven A.J. , Knaapen Paul , Escaned Javier , Koo Bon Kwon , Piek Jan J. , Kakuta Tsunekazu 
Published: June 2022

Background:
Coronary pressure indices such as fractional flow reserve are the standard for guiding elective revascularization. However, considering additional coronary flow parameters could further individualize and optimize the decision on revascularization. We aimed to investigate the potentially differential prognostic associations of elective percutaneous coronary intervention (PCI) according to coronary flow properties represented by coronary flow reserve (CFR), coronary flow capacity (CFC), and baseline CFC (bCFC).

Methods:
From the ILIAS Registry (Inclusive Invasive Physiological Assessment in Angina Syndromes) composed of 16 hospitals globally from 7 countries, patients with obstructive coronary artery disease who underwent invasive coronary physiological assessment were included (N=2370 vessels). We assessed effect measure modifications of the association of PCI and 5-year target vessel failure according to CFR, CFC, and bCFC either assessed by Doppler-technique or thermodilution-method.

Results:

The mean age of the population was 63.3 years, and there were 1322 (73.6%) males. Median fractional flow reserve was 0.85, and PCI was performed in 600 (25.3%) vessels. Reduced CFR, CFC, and abnormal bCFC were defined in 988 (41.7%), 542 (22.9%), and 600 (25.3%) vessels, respectively. Significant effect measure modifications were observed by CFC either in odds ratio (
P
=0.0018), additive (
P
=0.029), and hazard ratio scale (
P
=0.0002). The absolute risk of 5-year target-vessel failure was higher if treated by PCI in vessels with normal CFC by 1.8 (−1.7 to 5.3) percent, while that was lower by −5.9 (−12 to −0.1) percent in those with reduced CFC. CFR and bCFC were not significant effect modifiers in any scales. Similar associations were observed in per-patient analyses, whereas the findings were less robust.

Conclusions:
We observed qualitative effect measure modification of PCI and 5-year clinical outcomes according to CFC status in additive scale. CFR and bCFC were not robust effect modifiers. Therefore, CFC could be potentially used to optimize the patient selection for elective PCI treatment combined with fractional flow reserve.
Cardiovascular Magnetic Resonance for Rejection Surveillance After Cardiac Transplantation
Authors: Anthony Chris , Imran Muhammad , Pouliopoulos Jim , Emmanuel Sam , Iliff James , Liu Zhixin , Moffat Kirsten , Ru Qiu Min , McLean Catriona A. , Stehning Christian , Puntmann Valentina , Vassiliou Vass , Ismail Tevfik F. , Gulati Ankur , Prasad Sanjay , Graham Robert M. , McCrohon Jane , Holloway Cameron , Kotlyar Eugene , Muthiah Kavitha , Keogh Anne M. , Hayward Christopher S. , Macdonald Peter S. , Jabbour Andrew 
Published: June 2022

Background:
Endomyocardial biopsy (EMB) is the gold standard method for surveillance of acute cardiac allograft rejection (ACAR) despite its invasive nature. Cardiovascular magnetic resonance (CMR)–based myocardial tissue characterization allows detection of myocarditis. The feasibility of CMR-based surveillance for ACAR-induced myocarditis in the first year after heart transplantation is currently undescribed.

Methods:
CMR-based multiparametric mapping was initially assessed in a prospective cross-sectional fashion to establish agreement between CMR- and EMB-based ACAR and to determine CMR cutoff values between rejection grades. A prospective randomized noninferiority pilot study was then undertaken in adult orthotopic heart transplant recipients who were randomized at 4 weeks after orthotopic heart transplantation to either CMR- or EMB-based rejection surveillance. Clinical end points were assessed at 52 weeks.

Results:

Four hundred one CMR studies and 354 EMB procedures were performed in 106 participants. Forty heart transplant recipients were randomized. CMR-based multiparametric assessment was highly reproducible and reliable at detecting ACAR (area under the curve, 0.92; sensitivity, 93%; specificity, 92%; negative predictive value, 99%) with greater specificity and negative predictive value than either T1 or T2 parametric CMR mapping alone. High-grade rejection occurred in similar numbers of patients in each randomized group (CMR, n=7; EMB, n=8;
P
=0.74). Despite similarities in immunosuppression requirements, kidney function, and mortality between groups, the rates of hospitalization (9 of 20 [45%] versus 18 of 20 [90%]; odds ratio, 0.091;
P
=0.006) and infection (7 of 20 [35%] versus 14 of 20 [70%]; odds ratio, 0.192;
P
=0,019) were lower in the CMR group. On 15 occasions (6%), patients who were randomized to the CMR arm underwent EMB for clarification or logistic reasons, representing a 94% reduction in the requirement for EMB-based surveillance.

Conclusions:
A noninvasive CMR-based surveillance strategy for ACAR in the first year after orthotopic heart transplantation is feasible compared with EMB-based surveillance.

Registration:
HREC/13/SVH/66 and HREC/17/SVH/80. Australian New Zealand Clinical Trials Registry: ACTRN12618000672257.
Long-Term Evolution Experiment with Genetic Programming
Authors: Langdon William B. , Banzhaf Wolfgang 
Published: June 2022

Abstract
We evolve floating point Sextic polynomial populations of genetic programming binary trees for up to a million generations. We observe continued innovation but this is limited by tree depth. We suggest that deep expressions are resilient to learning as they disperse information, impeding evolvability, and the adaptation of highly nested organisms, and we argue instead for open complexity. Programs with more than 2,000,000,000 instructions (depth 20,000) are created by crossover. To support unbounded long-term evolution experiments in genetic programming (GP), we use incremental fitness evaluation and both SIMD parallel AVX 512-bit instructions and 16 threads to yield performance equivalent to 1.1 trillion GP operations per second, 1.1 tera GPops, on an Intel Xeon Gold 6136 CPU 3.00GHz server.
Young Learners’ Perceptions of Learning about Sexual and Gender-Based Harassment: The Struggle for Recognition in School
Authors: Goldschmidt-Gjerløw Beate 
Published: June 2022

Abstract
Based on participatory research with teachers and young learners’, this article explores students’ perceptions of learning about sexual and gender-based harassment in upper secondary school in Norway. Drawing upon theoretical considerations on recognition, intersectionality and legal literacy as educational capital, this article discusses approaches to teaching and learning that could ensure young learners’ rights to active participation and voice, which is an essential element for protection and prevention of harassment. The empirical material indicates that learners would like to learn more about these sensitive issues, although this applies to a greater extent for girls rather than boys. Their wish to learn more about harassment and abuse could be interpreted as a struggle for recognition, motivated by experiences of disrespect. However, defending one’s rights, and having someone defending one’s rights, in school requires both students’ and teachers’ legal literacy, which according to the empirical material is limited.
Innocent and Forgotten: Arresting Mothers and the Consequences for their Children
Authors: ter Vrugt P. J. H. , de Vocht D. L. F. 
Published: June 2022

Abstract
The arrest of a mother may have far reaching consequences for her child(ren). This article discusses the question whether in Dutch criminal proceedings these potential effects are sufficiently taken into account before, during and after the mother’s arrest. In order to answer this question, the potential negative effects the arrest may have on the children involved will be discussed. Next, attention will be paid to the international and European legal frameworks and their relevance for arresting mothers. The right of the child to be informed about the arrest, and European case law concerning the arrest of parents in the presence of their children, will be discussed. Finally, a critical analysis will be given of how the arrest of mothers is dealt with according to Dutch law and practice. Practical experiences will be drawn from fieldwork conducted in two Dutch detention centres.