bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low-dose interferon-alpha preconditioning and adoptive cell therapy in patients with metastatic melanoma refractory to standard (immune) therapies: a phase I/II study
Authors: Verdegaal Els , van der Kooij Monique K , Visser Marten , van der Minne Caroline , de Bruin Linda , Meij Pauline , Terwisscha van Scheltinga Anton , Welters Marij J , Santegoets Saskia , de Miranda Noel , Roozen Inge , Liefers Gerrit Jan , Kapiteijn Ellen , van der Burg Sjoerd H 
Published: April 2020

BackgroundAdoptive cell therapy (ACT) with tumor-reactive T cells has shown consistent clinical efficacy. We evaluated the response to ACT in combination with interferon alpha (IFNa) preconditioning in patients with stage IV metastatic melanoma, most of which were progressive on cytotoxic T-lymphocyte-associated protein 4 and/or programmed cell death protein 1 checkpoint blockade therapy.MethodsThirty-four patients were treated with ex vivo expanded tumor reactive T cells, derived from mixed lymphocyte autologous tumor cultures, or with autologous tumor-infiltrating lymphocytes and evaluated for clinical response. Clinical and immunological parameters associated with response were also evaluated.ResultsBest overall response defined as clinical benefit, comprising either complete response, partial response or stable disease >6 months, was observed in 29% of the patients. Forty-three per cent of the 14 immunotherapy-naïve patients and 20% of the 20 patients progressive on prior immunotherapy benefited from ACT. The overall survival (OS) was 90% versus 28.6% at 1 year and 46.7% versus 0% at 3 years follow-up, of responder and non-responder patients, respectively. Median OS was 36 versus 7 months, respectively. IFNa pretreatment resulted in leukopenia, neutropenia and lymphopenia, which was sustained during the treatment in clinical responders and associated with response. Differences in antigen specificity, but not in phenotype, cytokine profile or CD8+ T cell number of the ACT products correlated with clinical response. Cross-reactivity of the ACT products to one or more allogeneic human leukocyte antigen-matched melanoma cell lines was associated with short OS after treatment while the ACT products of very long-term survivors showed no cross-reactivity but recognized patient-specific neoantigens.ConclusionThis study demonstrates that ACT in combination with a mild IFNa preconditioning regimen can induce clinical benefit even in immunotherapy pretreated patients, although with lower success than in immunotherapy-naïve patients. ACT products comprising neoantigen reactivity may be more effective.
Ferromagnetism in the Kondo-lattice
Authors: Wagner Philipp , Wróbel Piotr , Eder Robert 
Published: April 2020

Abstract
We discuss the ferromagnetic phase of the planar Kondo lattice model using the bond fermion technique. For sufficiently small Kondo exchange we find a weakly ferromagnetic phase already for the weakly doped Kondo insulator. We present the phase diagram of the model and its quasiparticle band structure in the different phases.

Graphical abstract
Resonant scattering of Dice quasiparticles on oscillating quantum dots
Authors: Filusch Alexander , Wurl Christian , Fehske Holger 
Published: April 2020

Abstract
We consider a Dice model with Dirac cones intersected by a topologically flat band at the charge neutrality point and analyze the inelastic scattering of massless pseudospin-1 particles on a circular, gate-defined, oscillating barrier. Focusing on the resonant scattering regime at small energy of the incident wave, we calculate the reflection and transmission coefficients and derive explicit expressions for the time-dependent particle probability, current density and scattering efficiency within (Floquet) Dirac-Weyl theory, both in the near-field and the far-field. We discuss the importance of sideband scattering and Fano resonances in the quantum limit. When resonance conditions are fulfilled, the particle is temporarily trapped in vortices located close to edge of the quantum dot before it gets resubmitted with strong angular dependence. Interestingly even periodically alternating forward and backward radiation may occur. We also demonstrate the revival of resonant scattering related to specific fusiform boundary trapping profiles.

Graphical abstract
Long-Term Gemcitabine Treatment Reshapes the Pancreatic Tumor Microenvironment and Sensitizes Murine Carcinoma to Combination Immunotherapy
Authors: Principe Daniel R. , Narbutis Matthew , Kumar Sandeep , Park Alex , Viswakarma Navin , Dorman Matthew J. , Kamath Suneel D. , Grippo Paul J. , Fishel Melissa L. , Hwang Rosa F. , Thummuri Dinesh , Underwood Patrick W. , Munshi Hidayatullah G. , Trevino Jose G. , Rana Ajay 
Published: April 2020

AbstractPancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related death with a median survival time of 6–12 months. Most patients present with disseminated disease and the majority are offered palliative chemotherapy. With no approved treatment modalities for patients who progress on chemotherapy, we explored the effects of long-term gemcitabine administration on the tumor microenvironment to identify potential therapeutic options for chemorefractory PDAC. Using a combination of mouse models, primary cell line–derived xenografts, and established tumor cell lines, we first evaluated chemotherapy-induced alterations in the tumor secretome and immune surface proteins by high throughput proteomic arrays. In addition to enhancing antigen presentation and immune checkpoint expression, gemcitabine consistently increased the synthesis of CCL/CXCL chemokines and TGFβ-associated signals. These secreted factors altered the composition of the tumor stroma, conferring gemcitabine resistance to cancer-associated fibroblasts in vitro and further enhancing TGFβ1 biosynthesis. Combined gemcitabine and anti-PD-1 treatment in transgenic models of murine PDAC failed to alter disease course unless mice also underwent genetic or pharmacologic ablation of TGFβ signaling. In the setting of TGFβ signaling deficiency, gemcitabine and anti-PD-1 led to a robust CD8+ T-cell response and decrease in tumor burden, markedly enhancing overall survival. These results suggest that gemcitabine successfully primes PDAC tumors for immune checkpoint inhibition by enhancing antigen presentation only following disruption of the immunosuppressive cytokine barrier. Given the current lack of third-line treatment options, this approach warrants consideration in the clinical management of gemcitabine-refractory PDAC.Significance:These data suggest that long-term treatment with gemcitabine leads to extensive reprogramming of the pancreatic tumor microenvironment and that patients who progress on gemcitabine-based regimens may benefit from multidrug immunotherapy.See related commentary by Carpenter et al., p. 3070
APOBGenotypes andCDH13Haplotypes in the Cholesterol-Related Pathway Genes Predict Non–Small Cell Lung Cancer Survival
Authors: Deng Wei , Liu Hongliang , Luo Sheng , Clarke Jeffrey , Glass Carolyn , Su Li , Lin Lijuan , Christiani David C. , Wei Qingyi 
Published: April 2020

AbstractBackground:Several oncogenic signals are involved in the synthesis, metabolism, transportation, and modulation of cholesterol. However, the roles of genetic variants of the cholesterol pathway genes in cancer survival remain unclear.Methods:We investigated associations between 26,781 common SNPs in 209 genes of the cholesterol pathway and non–small cell lung cancer (NSCLC) survival by utilizing genotyping data from two published genome-wide association studies. We used multivariate Cox proportional hazards regression and expression quantitative trait loci analyses to identify survival-associated SNPs and their correlations with the corresponding mRNA expression, respectively. We also used the Kaplan–Meier survival analysis and bioinformatics functional prediction to further evaluate the identified independent SNPs.Results:We found five independent SNPs (APOB rs1801701C&gt;T; CDH13 rs35859010 C&gt;T, rs1833970 T&gt;A, rs254315 T&gt;C, and rs425904 T&gt;C) to be significantly associated with NSCLC survival in both discovery and replication datasets. When the unfavorable genotype (APOB rs1801701CC) and haplotypes (CDH13 rs35859010-rs1833970-rs254315-rs425904 C-A-T-C and T-T-T-T) were combined into a genetic score as the number of unfavorable genotypes/haplotypes (NUGH) in the multivariate analysis, an increased NUGH was associated with worse survival (Ptrend &lt; 0.0001). In addition, both APOB rs1801701T&lt;C and CDH13 rs425904C&lt;T were correlated with mRNA expression of the genes in normal lung tissues from the genotype-tissue expression project.Conclusions:Genetic variants of APOB and CDH13 in the cholesterol pathway were associated with NSCLC survival, possibly by affecting their gene expression.Impact:Genetic variants of APOB and CDH13 in the cholesterol pathway may provide new scientific insights into NSCLC prognosis.
Letting the GENIE Out of Its Bottle: Examining the Potential of Real-World Clinicogenomic Data
Authors: Castellanos Emily , Baxi Shrujal S. 
Published: April 2020

AbstractSummary:In this issue, Smyth and colleagues investigate the natural history of AKT1-mutant metastatic breast cancer using the AACR Project GENIE, a novel research platform comprised of real-world, clinicogenomic data. A rare subset of tumors, AKT1-mutant breast cancers demonstrated similar clinical and demographic characteristics and overall survival as AKT1–wild-type tumors, but a longer duration of therapy on mTOR inhibitors.See related article by Smyth et al., p. 526.
Anti-VEGF Treatment Enhances CD8+ T-cell Antitumor Activity by Amplifying Hypoxia
Authors: de Almeida Patricia E. , Mak Judy , Hernandez Genevive , Jesudason Rajiv , Herault Aurelie , Javinal Vincent , Borneo Jovencio , Kim Jeong M. , Walsh Kevin B. 
Published: April 2020

Abstract
Antiangiogenic therapies that target the VEGF pathway have been used clinically to combat cancer for over a decade. Beyond having a direct impact on blood vessel development and tumor perfusion, accumulating evidence indicates that these agents also affect antitumor immune responses. Numerous clinical trials combining antiangiogenic drugs with immunotherapies for the treatment of cancer are ongoing, but a mechanistic understanding of how disruption of tumor angiogenesis may impact immunity is not fully discerned. Here, we reveal that blockade of VEGF-A with a mAb to VEGF augments activation of CD8+ T cells within tumors and potentiates their capacity to produce cytokines. We demonstrate that this phenomenon relies on the disruption of VEGFR2 signaling in the tumor microenvironment but does not affect CD8+ T cells directly. Instead, the augmented functional capacity of CD8+ T cells stems from increased tumor hypoxia that initiates a hypoxia-inducible factor-1α program within CD8+ T cells that directly enhances cytokine production. Finally, combinatorial administration of anti-VEGF with an immunotherapeutic antibody, anti-OX40, improved antitumor activity over single-agent treatments. Our findings illustrate that anti-VEGF treatment enhances CD8+ T-cell effector function and provides a mechanistic rationale for combining antiangiogenic and immunotherapeutic drugs for cancer treatment.
Is the Affordable Care Act Medicaid Expansion Linked to Change in Rate of Ventricular Assist Device Implantation for Blacks and Whites?
Authors: Breathett Khadijah K. , Knapp Shannon M. , Wightman Patrick , Desai Archita , Mazimba Sula , Calhoun Elizabeth , Sweitzer Nancy K. 
Published: April 2020

Background:
The Affordable Care Act (ACA) has been associated with increased heart transplant listings among blacks, who are disproportionately uninsured. It is unclear whether the ACA is also associated with increased ventricular assist device implantation in blacks.

Methods:
Using Healthcare Cost and Utilization Project Data State Inpatient Databases from 19 states and Washington DC, we analyzed 1157 patients from early-adopter states (ACA Medicaid expansion by January 2014) and 785 patients from nonadopter states (no implementation from 2013 to 2014). Piecewise Poisson regression with a discontinuity was used to estimate change in census-adjusted rates of ventricular assist device implants by race and ACA adopter status 1 year before and after January 2014.

Results:

Following the ACA Medicaid expansion, the proportional change in rate increased significantly among blacks from early adopter (1.40 [95% CI, 1.12–1.75], pre 0.57/100 000 to post-ACA 0.80/100 000) but not nonadopter states (1.25 [95% CI, 0.98–1.58], pre 0.40/100 000 to post-ACA 0.50/100 000). However, the early and nonadopter changes in implantation rates were not statistically different from each other (
P
=0.50). There were no immediate changes in whites in either state group following the ACA Medicaid expansion (early adopter, 1.12 [95% CI, 0.98–1.29], pre 0.27/100 000 to post-ACA 0.30/100 000; nonadopter, 0.98 [95% CI, 0.82–1.16], pre 0.27/100 000 to post-ACA 0.26/100 000).

Conclusions:
Among eligible states participating in Healthcare Cost and Utilization Project Data State Inpatient Databases, the ACA was not associated with immediate changes in ventricular assist device implantation rates by race. Although a significant increase in implantation rate was observed among blacks from early-adopter states, the change was not statistically different from the change seen in nonadopter states.
Changes in Nut Consumption and Subsequent Cardiovascular Disease Risk Among US Men and Women: 3 Large Prospective Cohort Studies
Authors: Liu Xiaoran , Guasch‐Ferré Marta , Drouin‐Chartier Jean‐Philippe , Tobias Deirdre K. , Bhupathiraju Shilpa N. , Rexrode Kathryn M. , Willett Walter C. , Sun Qi , Li Yanping 
Published: April 2020

Background

We aim to evaluate the association of within‐individual changes in consumption of total and specific types of nuts and the subsequent risk of incident cardiovascular disease (
CVD
) in
US
men and women.

Methods and Results

We included 34 103 men from the HPFS (Health Professionals Follow‐Up Study) (1986–2012), 77 815 women from the NHS (Nurses’ Health Study) (1986–2012), and 80 737 women from the NHS
II
(1991–2013). We assessed nut consumption every 4 years using validated food frequency questionnaires. We used multivariable Cox proportional hazards regression models to examine the association between 4‐year changes in nut consumption and risk of confirmed
CVD
end points in the subsequent 4 years. Per 0.5 serving/day increase in total nut consumption was associated with lower risk of
CVD
(relative risk [RR], 0.92; 95%
CI
, 0.86–0.98), coronary heart disease (RR, 0.94; 95% CI, 0.89–0.99), and stroke (RR, 0.89; 95% CI, 0.83–0.95). Compared with individuals who remained nonconsumers in a 4‐year interval, those who had higher consumption of total nuts (≥0.5 servings/day) had a lower risk of
CVD
(RR, 0.75; 95% CI, 0.67–0.84), coronary heart disease (RR, 0.80; 95% CI, 0.69–0.93), and stroke (RR, 0.68; 95% CI, 0.57–0.82) in next 4 years. Individuals who decreased nut consumption by ≥0.50 servings/day had a higher risk of developing
CVD
(RR, 1.14; 95% CI, 0.99–1.32), coronary heart disease (RR, 1.06; 95% CI, 0.88–1.28), and stroke (RR, 1.28; 95% CI, 1.02–1.60) when compared with those who maintained their nut consumption.

Conclusions

Increasing total consumption of nuts and intake of individual types of nuts (eg, walnuts, other tree nuts, and peanuts) was associated with a subsequent lower risk of
CVD
. These data support the role of nut intake in the primary prevention of
CVD
.

Registration

URL
:
http://www.clini​caltr​ials.gov
. Unique identifiers:
NCT
00005152 and
NCT
00005182.
Characteristic Histopathological Findings and Cardiac Arrest Rhythm in Isolated Mitral Valve Prolapse and Sudden Cardiac Death
Authors: Han Hui‐Chen , Parsons Sarah A. , Teh Andrew W. , Sanders Prashanthan , Neil Christopher , Leong Trishe , Koshy Anoop N. , Vohra Jitendra K. , Kalman Jonathan M. , Smith Karen , O'Donnell David , Hare David L. , Farouque Omar , Lim Han S. 
Published: April 2020

Background

The association between mitral valve prolapse (MVP) and sudden death remains controversial. We aimed to describe histopathological changes in individuals with autopsy‐determined isolated
MVP
(
iMVP
) and sudden death and document cardiac arrest rhythm.

Methods and Results

The Australian National Coronial Information System database was used to identify cases of
iMVP
between 2000 and 2018. Histopathological changes in
iMVP
and sudden death were compared with 2 control cohorts matched for age, sex, height, and weight (1 group with noncardiac death and 1 group with cardiac death). Data linkage with ambulance services provided cardiac arrest rhythm for
iMVP
cases. From 77 221 cardiovascular deaths in the National Coronial Information System database, there were 376 cases with
MVP
. Individual case review yielded 71 cases of
iMVP
. Mean age was 49±18 years, and 51% were women. Individuals with
iMVP
had higher cardiac mass (447 g versus 355 g;
P
<0.001) compared with noncardiac death, but similar cardiac mass (447 g versus 438 g;
P
=0.64) compared with cardiac death. Individuals with
iMVP
had larger mitral valve annulus compared with noncardiac death (121 versus 108 mm;
P
<0.001) and cardiac death (121 versus 110 mm;
P
=0.002), and more left ventricular fibrosis (79% versus 38%;
P
<0.001) compared with noncardiac death controls. In those with
iMVP
and witnessed cardiac arrest, 94% had ventricular fibrillation.

Conclusions

Individuals with
iMVP
and sudden death have increased cardiac mass, mitral annulus size, and left ventricular fibrosis compared with a matched cohort, with cardiac arrest caused by ventricular fibrillation. The histopathological changes in
iMVP
may provide the substrate necessary for development of malignant ventricular arrhythmias.
White Matter Hyperintensity, Immediate Antihypertensive Treatment, and Functional Outcome After Acute Ischemic Stroke
Authors: Zhu Shiguang , Qian Sifan , Xu Tan , Peng Hao , Dong Ruiguo , Wang Dunjing , Yuan Xiaodong , Guo Libin , Zhang Yonghong , Geng Deqin , Zhong Chongke 
Published: April 2020

Background and Purpose—
It remains unknown that whether white matter hyperintensity (WMH) severity influences the effect of antihypertensive treatment in acute ischemic stroke. We aimed to investigate the effects of early antihypertensive treatment on death and disability among patients with acute ischemic stroke according to WMH severities.

Methods—
This study was a secondary analysis of the data from CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). Severity of WMH was evaluated using Fazekas rating scale score among 303 participants with available magnetic resonance imaging data and was categorized into none-mild WMH (Fazekas score 0–2) and moderate-severe WMH (Fazekas score 3–6). Functional outcome was death or major disability (modified Rankin Scale score of ≥3) at 14 days or hospital discharge and within 3 months.

Results—

WMH severity was significantly associated with an increased risk of death or major disability. Each 1 score increase in Fazekas score was associated with an adjusted odds ratio (95% CI) of 1.25 (1.03–1.51) for 14 days or hospital discharge and 1.39 (1.12–1.72) for 3-month functional outcome. There were no significant interactions between antihypertensive treatment and WMH severity (both
P
>0.1) on functional outcome at 14 days or hospital discharge and within 3 months. The neutral effects of immediate antihypertensive treatment were observed both in patients with moderate-severe WMH and none-mild WMH.

Conclusions—
Participants with higher WMH burden had increased risk of death or major disability after acute ischemic stroke. Early antihypertensive treatment had a neutral effect on clinical outcomes among acute ischemic stroke patients with a variety of WMH severities.

Registration—

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01840072.
Halakhic Truth and Erroneous Ruling: a Study of the Philosophy of Halakhah in the School of R. Nissim of Gerona—R. Isaac Bar Sheshet and R. Ḥasdai Crescas
Authors: Ravitsky Aviram 
Published: April 2020

Abstract
This study analyzes the attitude toward the conflict between halakhah and science in the thought of two halakhic authorities of fifteenth-century Spain who developed the ideas of their master, R. Nissim of Gerona, in different directions. R. Isaac bar Sheshet Perfet (Rivash) privileged halakhah over science for epistemological reasons because of its basis in revelation and tradition, but it appears that R. Ḥasdai Crescas stressed faith in the halakhic authority of the sages, even in cases of an erroneous ruling, as a way to increase the believing Jew’s motivation to serve God.
Sharīʿah-compliant or Sharīʿah-based? The Changing Ethical Discourse of Islamic Finance
Authors: Calder Ryan 
Published: April 2020

Abstract
Observers call upon Islamic financial institutions to move beyond offering merely Sharīʿah-compliant instruments toward offering more Sharīʿah-based ones. But when did these terms come into usage, and why? What precisely do people mean by ‘Sharīʿah-based’? In this article we argue that the term ‘Sharīʿah-compliant’ emerged in the 1990s and allowed Islamic finance institutions to leave behind scandals of the 1980s, presenting Islamic finance anew as a technically rational project grounded in Sharīʿah expertise. In contrast, the call for Sharīʿah-based finance became popular in the 2000s, and especially after the 2008 global financial crisis, which made systemic stability and product transparency pressing concerns. Usages of ‘Sharīʿah-based’ fall into three categories: those that stress separation from conventional finance, those that stress authenticity, and those that stress welfare. This definitional multiplicity is not a problem but rather a starting point for debate and a sign of Islamic finance’s growing maturity as an ethical project.
Cinematografia e ispirazione letteraria socialista
Authors: Giacci Vittorio 
Published: April 2020

Il saggio affronta il tema della relazione tra letteratura e cinema sia in termini generali che in ambito più strettamente politico, soffermandosi sugli adattamenti di opere letterarie scritte da autori di area e ispirazione socialista, ma anche su opere cinematografiche, tratte da soggetti originali, realizzate da registi che si sono riconosciuti, stabilmente o temporaneamente, nel socialismo italiano. Si vuole colmare l’evidente lacuna di una critica che ha preferito guardare alle esperienze di autori che palesavano altre ispirazioni, come quelle cattolica e comunista, benché il contributo di cineasti dell’area socialista sia stato altrettanto, se non più ampio e profondo, come il presente saggio intende dimostrare. Lo studio considera anche l’apporto fornito dai socialisti laddove hanno operato, con incarichi di responsabilità, nelle politiche culturali italiane, partecipando anche alla definizione legislativa di settore, con posizioni di rilievo in importanti istituzioni del cinema pubblico (Centro Sperimentale di Cinematografia, Cinecittà, Italnoleggio, Istituto Luce), senza escludere la Biennale, i vari festival e le organizzazioni del settore pubblico. Ne risulta il ruolo determinante giocato dal pensiero e dai valori socialisti nel quadro del rinnovamento culturale del paese attuato mediante lo strumento della settima arte. La relazione cinema/socialismo non può essere colta in tutte le sue articolazioni se non la si inscrive in un più ampio contesto storico/politico e all’interno delle due anime che hanno da sempre caratterizzato le vicende del Partito Socialista, la tensione massimalista e la progettualità riformista, le scissioni ed i tentativi di riunificazione, l’unità d’azione e il contrasto a sinistra tra Partito Comunista e Partito Socialista, la propensione del primo al monopolio culturale ed a tacciare di “revisionismo” qualunque tentativo di innovazione politica che fosse al passo con i tempi e la refrattarietà del secondo a ogni forma di immobilismo ideologico, di egemonia culturale e di subalternità.