bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineering adoptive T cell therapy to co-opt Fas ligand-mediated death signaling in ovarian cancer enhances therapeutic efficacy
Authors: Anderson Kristin G , Oda Shannon K , Bates Breanna M , Burnett Madison G , Rodgers Suarez Magdalia , Ruskin Susan L , Greenberg Philip D 
Published: March 2022

BackgroundIn the USA, more than 50% of patients with ovarian cancer die within 5 years of diagnosis, highlighting the need for therapeutic innovations. Mesothelin (MSLN) is a candidate immunotherapy target; it is overexpressed by ovarian tumors and contributes to malignant/invasive phenotypes, making tumor antigen loss disadvantageous. We previously showed that MSLN-specific T cell receptor (TCR)-engineered T cells preferentially accumulate within established tumors, delay tumor growth, and significantly prolong survival in the ID8VEGFmouse model that replicates many aspects of human disease. However, T cell persistence and antitumor activity were not sustained. We therefore focused on Fas/FasL signaling that can induce activation-induced cell death, an apoptotic mechanism that regulates T cell expansion. Upregulation of FasL by tumor cells and tumor vasculature has been detected in the tumor microenvironment (TME) of human and murine ovarian cancers, can induce apoptosis in infiltrating, Fas (CD95) receptor-expressing lymphocytes, and can protect ovarian cancers from tumor-infiltrating lymphocytes.MethodsTo overcome potential FasL-mediated immune evasion and enhance T cell responses, we generated an immunomodulatory fusion protein (IFP) containing the Fas extracellular binding domain fused to a 4-1BB co-stimulatory domain, rather than the natural death domain. Murine T cells were engineered to express an MSLN-specific TCR (TCR1045), alone or with the IFP, transferred into ID8VEGFtumor-bearing mice and evaluated for persistence, proliferation, cytokine production and efficacy. Human T cells were similarly engineered to express an MSLN-specific TCR (TCR530) alone or with a truncated Fas receptor or a Fas-4-1BB IFP and evaluated for cytokine production and tumor lysis.ResultsRelative to murine T cells expressing only TCR1045, T cells expressingbothTCR1045and a Fas-4-1BB IFP preferentially persisted in the TME of tumor-bearing mice, with improved T cell proliferation and survival. Moreover, TCR1045/IFP+T cells significantly prolonged survival in tumor-bearing mice, compared with TCR1045-only T cells. Human T cells expressing TCR530and a Fas-4-1BB IFP exhibit enhanced functional activity and viability compared with cells with only TCR530.ConclusionsAs many ovarian tumors overexpress FasL, an IFP that converts the Fas-mediated death signal into pro-survival and proliferative signals may be used to enhance engineered adoptive T cell therapy for patients.
Neurocognitive impairment in night and shift workers: a meta-analysis of observational studies
Authors: Vlasak Thomas , Dujlovic Tanja , Barth Alfred 
Published: March 2022

ObjectiveShift work is an essential element of modern labour, ensuring ideal conditions of service for today’s economy and society. Despite the beneficial properties, its impact on the neurobehavioural performance of exposed subjects remains controversial. This meta-analysis aimed to provide the first summarising effects regarding the association between shift work exposure and different cognitive functions.MethodsA literature search was performed using the databases PubMed, PsyINFO, PsyARTICLES, MedLine, PsycNET and Scopus including eligible studies up to April 2021 that compared shift workers with non-shift workers regarding neurobehavioural performance tests. We carried out a random-effects model using Hedges’ g as a meta-analytical effect size with a restricted likelihood estimator to summarise the mean differences between the exposure group and controls. Positive effect sizes indicate higher performance for non-shift workers. The heterogeneity of effect sizes was addressed by sensitivity analysis using funnel plots, Egger’s tests, p-curve analysis, meta-regressions and subgroup analysis.ResultsWe included 18 studies resulting in a total sample of 18 802 participants and 37 effect sizes concerning six different neurobehavioural outcomes. Our results showed significantly worse performance in shift workers compared with non-shift workers in the following cognitive functions with g (95% CI): processing speed 0.16 (0.02 to 0.30), working memory 0.28 (0.51 to 0.50), psychomotor vigilance 0.21 (0.05 to 0.37), cognitive control 0.86 (0.45 to 1.27) and visual attention 0.19 (0.11 to 0.26).ConclusionsWe provide the first meta-analytical findings that associate shift work with decreased cognitive performance in processing speed, working memory, psychomotor vigilance, cognitive control and visual attention.
Risk of ischaemic and haemorrhagic stroke in Chinese undergoing percutaneous coronary intervention treated with potent P2Y12 inhibitor versus clopidogrel
Authors: Ng Andrew Kei-Yan , Ng Pauline Yeung , Ip April , Lau Kui Kai , Siu Chung-Wah 
Published: March 2022

BackgroundStroke after acute coronary syndrome (ACS) can be devastating. It is uncertain whether the risks of ischaemic stroke or intracranial haemorrhage (ICH) are associated with different choices of P2Y12 inhibitors (potent P2Y12 inhibitors such as ticagrelor and prasugrel vs clopidogrel). Even though East Asians are known to have different thrombotic and haemorrhagic profiles from Caucasians, data on Chinese patients are sparse.MethodThis was a retrospective cohort study conducting in Chinese patients with ACS who underwent first-ever percutaneous coronary intervention from 14 hospitals in Hong Kong between 2010 and 2017. The primary efficacy endpoint was ischaemic stroke. The secondary efficacy endpoint was a composite outcome of thrombotic events including all-cause mortality, non-fatal myocardial infarction and ischaemic stroke. The primary safety endpoint was ICH. The secondary safety endpoint was a composite of major bleeding events.ResultsAfter adjustment of baseline characteristics by 1:1 propensity score matching, a total of 6220 patients (3110 on each group) were analysed. Compared with clopidogrel, potent P2Y12 inhibitors were associated with a lower risk of ischaemic stroke (HR 0.57; 95% CI 0.37 to 0.87; p=0.008) and a lower risk of thrombotic events (HR 0.77; 95% CI 0.66 to 0.90; p=0.001). Potent P2Y12 inhibitor was associated with similar risk of ICH (HR 0.65; 95% CI 0.34 to 1.25, p=0.20) and major bleeding (HR 0.83; 95% CI 0.68 to 1.01, p=0.069).ConclusionsPotent P2Y12 inhibitors were associated with a lower adjusted risk of ischaemic stroke and thrombotic events, compared with clopidogrel. The risks of ICH and major bleeding were similar.
Probing spin-dependent dark matter interactions with $$^6$$Li
Authors: Angloher G. , Benato G. , Bento A. , Bertoldo E. , Bertolini A. , Breier R. , Bucci C. , Canonica L. , D’Addabbo A. , Di Lorenzo S. , Einfalt L. , Erb A. , Feilitzsch F. v. , Ferreiro Iachellini N. , Fichtinger S. , Fuchs D. , Fuss A. , Garai A. , Ghete V. M. , Gorla P. , Gupta S. , Hauff D. , Ješkovský M. , Jochum J. , Kaznacheeva M. , Kinast A. , Kluck H. , Kraus H. , Langenkämper A. , Mancuso M. , Marini L. , Mokina V. , Nilima A. , Olmi M. , Ortmann T. , Pagliarone C. , Palušová V. , Pattavina L. , Petricca F. , Potzel W. , Povinec P. , Pröbst F. , Pucci F. , Reindl F. , Rothe J. , Schäffner K. , Schieck J. , Schmiedmayer D. , Schönert S. , Schwertner C. , Stahlberg M. , Stodolsky L. , Strandhagen C. , Strauss R. , Usherov I. , Wagner F. , Willers M. , Zema V. 
Published: March 2022

AbstractCRESST is one of the most prominent direct detection experiments for dark matter particles with sub-GeV/c$$^2$$

2

mass. One of the advantages of the CRESST experiment is the possibility to include a large variety of nuclides in the target material used to probe dark matter interactions. In this work, we discuss in particular the interactions of dark matter particles with protons and neutrons of $$^{6}$$

6

Li. This is now possible thanks to new calculations on nuclear matrix elements of this specific isotope of Li. To show the potential of using this particular nuclide for probing dark matter interactions, we used the data collected previously by a CRESST prototype based on LiAlO$$_2$$

2

and operated in an above ground test-facility at Max-Planck-Institut für Physik in Munich, Germany. In particular, the inclusion of $$^{6}$$

6

Li in the limit calculation drastically improves the result obtained for spin-dependent interactions with neutrons in the whole mass range. The improvement is significant, greater than two order of magnitude for dark matter masses below 1 GeV/c$$^2$$

2

, compared to the limit previously published with the same data.
Active Exploration for Neural Global Illumination of Variable Scenes
Authors: Diolatzis Stavros , Philip Julien , Drettakis George 
Published: March 2022

Neural rendering algorithms introduce a fundamentally new approach for photorealistic rendering, typically by learning a neural representation of illumination on large numbers of ground truth images. When training for a given
variable
scene, such as changing objects, materials, lights, and viewpoint, the space

\( \mathcal {D} \)

of possible training data instances quickly becomes unmanageable as the dimensions of variable parameters increase. We introduce a novel
Active Exploration
method using Markov Chain Monte Carlo, which
explores

\( \mathcal {D} \)

, generating samples (i.e., ground truth renderings) that best help training and interleaves training and on-the-fly sample data generation. We introduce a self-tuning sample reuse strategy to minimize the expensive step of rendering training samples. We apply our approach on a neural generator that learns to render novel scene instances given an explicit parameterization of the scene configuration. Our results show that Active Exploration trains our network much more efficiently than uniformly sampling and, together with our resolution enhancement approach, achieves better quality than uniform sampling at convergence. Our method allows interactive rendering of hard light transport paths (e.g., complex caustics), which require very high samples counts to be captured, and provides dynamic scene navigation and manipulation, after training for 5 to 18 hours depending on required quality and variations.
Chemotherapy-Induced Collagen IV Drives Cancer Cell Motility through Activation of Src and Focal Adhesion Kinase
Authors: Fatherree Jackson P. , Guarin Justinne R. , McGinn Rachel A. , Naber Stephen P. , Oudin Madeleine J. 
Published: March 2022

Abstract

Triple-negative breast cancer (TNBC) is the most aggressive and deadly subtype of breast cancer, accounting for 30,000 cases annually in the United States. While there are several clinical trials ongoing to identify new agents to treat TNBC, the majority of patients with TNBC are treated with anthracycline- or taxane-based chemotherapies in the neoadjuvant setting, followed by surgical resection and adjuvant chemotherapy. While many patients respond well to this approach, as many as 25% will suffer local or metastatic recurrence within 5 years. Understanding the mechanisms that drive recurrence after chemotherapy treatment is critical to improving survival for patients with TNBC. It is well established that the extracellular matrix (ECM), which provides structure and support to tissues, is a major driver of tumor growth, local invasion, and dissemination of cancer cells to distant metastatic sites. In the present study, we show that decellularized ECM (dECM) obtained from chemotherapy-treated mice increases motility of treatment-naïve breast cancer cells compared with vehicle-treated dECM. Tandem-mass–tag proteomics revealed that anthracycline- and taxane-based chemotherapies induce drug-specific changes in tumor ECM composition. The basement membrane protein collagen IV was significantly upregulated in the ECM of chemotherapy-treated mice and patients treated with neoadjuvant chemotherapy. Collagen IV drove invasion via activation of Src and focal adhesion kinase signaling downstream of integrin α1 and α2, and inhibition of collagen IV–driven signaling decreased motility in chemotherapy-treated dECM. These studies provide a novel mechanism by which chemotherapy may induce metastasis via its effects on ECM composition.

Significance:
Cytotoxic chemotherapy induces significant changes in the composition of tumor ECM, inducing a more invasive and aggressive phenotype in residual tumor cells following chemotherapy.
The Polarity and Specificity of Antiviral T Lymphocyte Responses Determine Susceptibility to SARS-CoV-2 Infection in Patients with Cancer and Healthy Individuals
Authors: Fahrner Jean-Eudes , Lahmar Imran , Goubet Anne-Gaëlle , Haddad Yacine , Carrier Agathe , Mazzenga Marine , Drubay Damien , Alves Costa Silva Carolina ,   Lyon COVID Study Group, de Sousa Eric , Thelemaque Cassandra , Melenotte Cléa , Dubuisson Agathe , Geraud Arthur , Ferrere Gladys , Birebent Roxanne , Bigenwald Camille , Picard Marion , Cerbone Luigi , Lérias Joana R. , Laparra Ariane , Bernard-Tessier Alice , Kloeckner Benoît , Gazzano Marianne , Danlos François-Xavier , Terrisse Safae , Pizzato Eugenie , Flament Caroline , Ly Pierre , Tartour Eric , Benhamouda Nadine , Meziani Lydia , Ahmed-Belkacem Abdelhakim , Miyara Makoto , Gorochov Guy , Barlesi Fabrice , Trubert Alexandre , Ungar Benjamin , Estrada Yeriel , Pradon Caroline , Gallois Emmanuelle , Pommeret Fanny , Colomba Emeline , Lavaud Pernelle , Deloger Marc , Droin Nathalie , Deutsch Eric , Gachot Bertrand , Spano Jean-Philippe , Merad Mansouria , Scotté Florian , Marabelle Aurélien , Griscelli Frank , Blay Jean-Yves , Soria Jean-Charles , Merad Miriam , André Fabrice , Villemonteix Juliette , Chevalier Mathieu F. , Caillat-Zucman Sophie , Fenollar Florence , Guttman-Yassky Emma , Launay Odile , Kroemer Guido , La Scola Bernard , Maeurer Markus , Derosa Lisa , Zitvogel Laurence 
Published: March 2022

Abstract

Vaccination against coronavirus disease 2019 (COVID-19) relies on the in-depth understanding of protective immune responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We characterized the polarity and specificity of memory T cells directed against SARS-CoV-2 viral lysates and peptides to determine correlates with spontaneous, virus-elicited, or vaccine-induced protection against COVID-19 in disease-free and cancer-bearing individuals. A disbalance between type 1 and 2 cytokine release was associated with high susceptibility to COVID-19. Individuals susceptible to infection exhibited a specific deficit in the T helper 1/T cytotoxic 1 (Th1/Tc1) peptide repertoire affecting the receptor binding domain of the spike protein (S1-RBD), a hotspot of viral mutations. Current vaccines triggered Th1/Tc1 responses in only a fraction of all subject categories, more effectively against the original sequence of S1-RBD than that from viral variants. We speculate that the next generation of vaccines should elicit Th1/Tc1 T-cell responses against the S1-RBD domain of emerging viral variants.

Significance:
This study prospectively analyzed virus-specific T-cell correlates of protection against COVID-19 in healthy and cancer-bearing individuals. A disbalance between Th1/Th2 recall responses conferred susceptibility to COVID-19 in both populations, coinciding with selective defects in Th1 recognition of the receptor binding domain of spike.
See related commentary by McGary and Vardhana, p. 892.
This article is highlighted in the In This Issue feature, p. 873
Phosphoantigen-Stimulated γδ T Cells Suppress Natural Killer–Cell Responses to Missing-Self
Authors: Walwyn-Brown Katherine , Pugh Jason , Cocker Alexander T.H. , Beyzaie Niassan , Singer Bernhard B. , Olive Daniel , Guethlein Lisbeth A. , Parham Peter , Djaoud Zakia 
Published: March 2022

Abstractγδ T cells stimulated by phosphoantigens (pAg) are potent effectors that secrete Th1 cytokines and kill tumor cells. Consequently, they are considered candidates for use in cancer immunotherapy. However, they have proven only moderately effective in several clinical trials. We studied the consequences of pAg-stimulated γδ T-cell interactions with natural killer (NK) cells and CD8+ T cells, major innate and adaptive effectors, respectively. We found that pAg-stimulated γδ T cells suppressed NK-cell responses to “missing-self” but had no effect on antigen-specific CD8+ T-cell responses. Extensive analysis of the secreted cytokines showed that pAg-stimulated γδ T cells had a proinflammatory profile. CMV-pp65–specific CD8+ T cells primed with pAg-stimulated γδ T cells showed little effect on responses to pp65-loaded target cells. By contrast, NK cells primed similarly with γδ T cells had impaired capacity to degranulate and produce IFNγ in response to HLA class I–deficient targets. This effect depended on BTN3A1 and required direct contact between NK cells and γδ T cells. γδ T-cell priming of NK cells also led to a downregulation of NKG2D and NKp44 on NK cells. Every NK-cell subset was affected by γδ T cell–mediated immunosuppression, but the strongest effect was on KIR+NKG2A– NK cells. We therefore report a previously unknown function for γδ T cells, as brakes of NK-cell responses to “missing-self.” This provides a new perspective for optimizing the use of γδ T cells in cancer immunotherapy and for assessing their role in immune responses to pAg-producing pathogens.See related Spotlight by Kabelitz, p. 543.
Cardiovascular Risk for Patients With and Without Schizophrenia, Schizoaffective Disorder, or Bipolar Disorder
Authors: Rossom Rebecca C. , Hooker Stephanie A. , O’Connor Patrick J. , Crain A. Lauren , Sperl‐Hillen JoAnn M. 
Published: March 2022

Background
To compare estimated 10‐year and 30‐year cardiovascular risk in primary care patients with and without serious mental illness (SMI; bipolar disorder, schizophrenia, or schizoaffective disorder).

Methods and Results

All patients aged 18 to 75 years with a primary care visit in January 2016 to September 2018 were included and were grouped into those with and without SMI using diagnosis codes. Ten‐year cardiovascular risk was estimated using atherosclerotic cardiovascular disease scores for patients aged 40 to 75 years without cardiovascular disease; 30‐year cardiovascular risk was estimated using Framingham risk scores for patients aged 18 to 59 years without cardiovascular disease. Demographic, vital sign, medication, diagnosis, and health insurance data were collected from the electronic health record by a clinical decision support system. Descriptive statistics examined unadjusted differences, while general linear models examined differences for continuous variables and logistic regression models for categorical variables. Models were then adjusted for age, sex, race, ethnicity, and insurance type. A total of 11 333 patients with SMI and 579 924 patients without SMI were included. After covariate adjustment, 10‐year cardiovascular risk was significantly higher in patients with SMI (mean, 9.44%; 95% CI, 9.29%–9.60%) compared with patients without SMI (mean, 7.99%; 95% CI, 7.97–8.02). Similarly, 30‐year cardiovascular risk was significantly higher in those with SMI (25% of patients with SMI in the highest‐risk group compared with 11% of patients without SMI;
P
<0.001). The individual cardiovascular risk factors contributing most to increased risk for those with SMI were elevated body mass index and smoking. Among SMI subtypes, patients with bipolar disorder had the highest 10‐year cardiovascular risk, while patients with schizoaffective disorder had the highest 30‐year cardiovascular risk.

Conclusions
The significantly increased cardiovascular risk associated with SMI is evident even in young adults. This suggests the importance of addressing uncontrolled major cardiovascular risk factors in those with SMI at as early an age as possible.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02451670.
Prognostic Cardiac Magnetic Resonance Markers of Left Ventricular Involvement in Arrhythmogenic Cardiomyopathy for Predicting Heart Failure Outcomes
Authors: Chun Kyeong‐Hyeon , Oh Jaewon , Hong Yoo Jin , Yu Hee Tae , Lee Chan Joo , Kim Tae‐Hoon , Joung Boyoung , Pak Hui‐Nam , Lee Moon‐Hyoung , Kim Young Jin , Kang Seok‐Min 
Published: March 2022

Background
Left ventricular (LV) involvement is frequently observed in arrhythmogenic cardiomyopathy (ACM). We investigated the association of LV myocardial assessment using cardiac magnetic resonance (CMR) with clinical outcomes including heart failure (HF)‐related events in ACM.

Methods and Results

We retrospectively analyzed 60 patients with ACM between 2005 and 2020 according to the 2010 Task Force Criteria and assessed HF‐related events (HF hospitalization, heart transplantation, and cardiac death) and ventricular tachycardia events. We analyzed CMR findings including late gadolinium enhancement (LGE) in all subjects and obtained mapping values (native T1, extracellular volume, and T2) on 30 (50%) patients out of them. Among the study population (mean age 49 years, 77% male), 41 (68%) patients had LV LGE. During a median follow‐up of 34 months, there were 13 (22%) HF‐related events, and 20 (30%) ventricular tachycardia events. Kaplan‐Meier survival analysis revealed that HF‐related events occurred only in patients with LV LGE (+) (versus LV LGE (‐), log‐rank
P
=0.006), and the events were not significantly different regarding right ventricular LGE (log‐rank
P
>0.999). When categorized by median value for each mapping parameter, HF‐related events occurred more in patients with higher native T1 (versus lower native T1, log‐rank
P
=0.002), and higher T2 (versus lower T2, log‐rank
P
=0.002), higher extracellular volume (versus lower extracellular volume, log‐rank
P
=0.002). However, regarding ventricular tachycardia events, there were no significant differences according to these CMR markers.

Conclusions
LV myocardial assessment using CMR with LGE imaging and native T1, T2, and extracellular volume markers were significantly associated with HF‐related event risk in patients with ACM.
The Suspension of the Portuguese Inquisition, 1674 to 1681: The Female Perspective
Authors: Lloyd Ana Paula 
Published: March 2022

Abstract
Using trials and wills of women arrested in the Portuguese inquisitorial purges of New Christian families between 1672 and 1674, which gave rise to negotiations for a General Pardon and unprecedented suspension of the Inquisition, this article argues that there was a concerted strategy of female education amongst New Christian families, teaching literacy and business savvy to girls. This was not as a tool of empowerment or self-determination against a paternalistic society, but a necessity for the family to function under the scrutiny of neighbors and threat of inquisitorial persecution. Literacy was both a political strategy, a tool that could be used to undermine and evade the inquisition’s codes of secrecy, and a way to ensure the family and its vitally important business networks survived in the diaspora. Exploring the idea that reading and writing can be political acts, I will examine here what literacy meant for the practicality of lives lived in the shadow of the inquisition and diaspora.