bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exosomal CD73 from serum of patients with melanoma suppresses lymphocyte functions and is associated with therapy resistance to anti-PD-1 agents
Authors: Turiello Roberta , Capone Mariaelena , Morretta Elva , Monti Maria Chiara , Madonna Gabriele , Azzaro Rosa , Del Gaudio Pasquale , Simeone Ester , Sorrentino Antonio , Ascierto Paolo A , Morello Silvana 
Published: March 2022

BackgroundCD73 is an ectonucleotidase producing the immunosuppressor mediator adenosine. Elevated levels of circulating CD73 in patients with cancer have been associated with disease progression and poor response to immunotherapy. Immunosuppressive pathways associated with exosomes can affect T-cell function and the therapeutic efficacy of anti-programmed cell-death protein 1 (anti-PD-1) therapy. Here, we conducted a retrospective pilot study to evaluate levels of exosomal CD73 before and early during treatment with anti-PD-1 agents in patients with melanoma and its potential contribution to affect T-cell functions and to influence the clinical outcomes of anti-PD-1 monotherapy.MethodsExosomes were isolated by mini size exclusion chromatography from serum of patients with melanoma (n=41) receiving nivolumab or pembrolizumab monotherapy. Expression of CD73 and programmed death-ligand 1 (PD-L1) were evaluated on exosomes enriched for CD63 by on-bead flow cytometry. The CD73 AMPase activity was evaluated by mass spectrometry, also in the presence of selective inhibitors of CD73. Interferon (IFN)-γ production and granzyme B expression were measured in CD3/28 activated T cells incubated with exosomes in presence of the CD73 substrate AMP. Levels of CD73 and PD-L1 on exosomes were correlated with therapy response. Exosomes isolated from healthy subjects were used as control.ResultsIsolated exosomes carried CD73 on their surface, which is enzymatically active in producing adenosine. Incubation of exosomes with CD3/28 activated T cells in the presence of AMP resulted in a significant reduction of IFN-γ release, which was reversed by the CD73 inhibitor APCP or by the selective A2A adenosine receptor antagonist ZM241385. Expression levels of exosomal CD73 from serum of patients with melanoma were not significantly different from those in healthy subjects. Early on-treatment, expression levels of both CD73 and PD-L1 on exosomes isolated from patients receiving pembrolizumab or nivolumab monotherapy were significantly increased compared with baseline. Early during therapy exosomal PD-L1 increased in responders, while exosomal CD73 resulted significantly increased in non-responders.ConclusionsCD73 expressed on exosomes from serum of patients with melanoma produces adenosine and contributes to suppress T-cell functions. Early on-treatment, elevated expression levels of exosomal CD73 might affect the response to anti-PD-1 agents in patients with melanoma who failed to respond to therapy.
Estimating QCD-factorization amplitudes through SU(3) symmetry in $$B\rightarrow P P$$ decays
Authors: Huber Tobias , Tetlalmatzi-Xolocotzi Gilberto 
Published: March 2022

AbstractWe estimate the potential size of the weak annihilation amplitudes in QCD factorization as allowed by experimental data. To achieve this goal, we establish a connection between the amplitudes in the QCD factorization and the so-called topological and SU(3)-invariant descriptions. Our approach is based purely on the analysis of the tensor structure of the decay amplitudes. By focusing on the processes $$B\rightarrow P P$$

B
→
P
P

and considering data from CP asymmetries and branching fractions, we perform a global fit to the SU(3)-irreducible quantities assuming minimal theoretical bias. Subsequently we translate the outcome to the QCD factorization decomposition, and find that the most constrained weak annihilation amplitudes are below 0.04. However, in view of the large uncertainties in several of the experimental input parameters, values up to $$\sim 0.3$$

∼
0.3

are allowed in certain cases.
Testing the upper bound on the speed of scrambling with an analogue of Hawking radiation using trapped ions
Authors: Tian Zehua , Lin Yiheng , Fischer Uwe R. , Du Jiangfeng 
Published: March 2022

AbstractThe Lyapunov exponent of a quantum system has been predicted to be bounded by $$\lambda _L\le 2\pi \,T/\hbar $$

λ
L

≤
2
π

T
/
ħ

, where T is its temperature, as established by Maldacena, Shenker, and Stanford (MSS). This bound plays an important role in studying very diverse topics of physics, ranging from the dynamics of interacting many-body systems to the black hole information problem, and it is saturated when the system under consideration is the exact holographic dual of a black hole. Based on the fact that an inverted harmonic oscillator (IHO) may exhibit the behavior of thermal energy emission, in close analogy to the Hawking radiation emitted by black holes, we propose using a trapped ion as an implementation of the IHO to verify, in a concrete analogue-gravity system, whether the MSS bound can be identically saturated. To this end, we provide prescriptions for experimentally observing the scattering process at the IHO potential, which yields an analogue of Hawking radiation, as well as for how to measure the corresponding out-of-time-ordered correlation function (OTOC), diagnosing quantum chaos, in this thermally excited semiclassical system. We theoretically show, for an experimentally realizable analogue-gravity setup, that the effective Hawking temperature of the trapped-ion-IHO indeed matches the upper MSS bound for the speed of scrambling.
Mass-derivative relations for leptogenesis
Authors: Blažek Tomáš , Maták Peter 
Published: March 2022

AbstractIn this work, a diagrammatic representation of thermal mass effects is derived from the S-matrix unitarity both in the classical and quantum Boltzmann equations. Within the example of the seesaw type-I leptogenesis, we discuss the connection of the Higgs thermal mass and the cancelations of infrared divergences in zero- and finite-temperature calculations of the right-handed neutrino decay and scattering processes.
Conduit CAR: Redirecting CAR T-Cell Specificity with A Universal and Adaptable Bispecific Antibody Platform
Authors: Borrok M. Jack , Li Yonghai , Harvilla Paul B. , Vellalore Maruthachalam Bharathikumar , Tamot Ninkka , Prokopowitz Christine , Chen Jun , Venkataramani Sathya , Grewal Iqbal S. , Ganesan Rajkumar , Singh Sanjaya 
Published: March 2022

The success of chimeric antigen receptor (CAR) T-cell therapy against hematologic malignancies has altered the treatment paradigm for patients with these diseases. Nevertheless, the occurrence of relapse due to antigen escape or heterogeneous antigen expression on tumors remains a challenge for first-generation CAR T-cell therapies as only a single tumor antigen can be targeted. To address this limitation and to add a further level of tunability and control to CAR T-cell therapies, adapter or universal CAR T-cell approaches use a soluble mediator to bridge CAR T cells with tumor cells. Adapter CARs allow simultaneous or sequential targeting of multiple tumor antigens, control of immune synapse geometry, dose control, and the potential for improved safety. Herein, we described a novel CAR T-cell adapter platform that relies on a bispecific antibody (BsAb) targeting both a tumor antigen and the GGGGS (G4S) linker commonly used in single-chain Fv (ScFv) domains expressed on CAR T-cell surfaces. We demonstrated that the BsAb can bridge CAR T cells to tumor cells and potentiate CAR T-cell activation, proliferation, and tumor cell cytolysis. The cytolytic activity of CAR T-cells was redirected to different tumor antigens by changing the BsAb in a dose-dependent manner. This study highlights the potential of G4S-displaying CAR T cells to be redirected to engage alternative tumor-associated antigens (TAA).Significance:New approaches are needed to address relapsed/refractory disease and manage potential toxicities associated with CAR T-cell therapy. We describe an adapter CAR approach to redirect CAR T cells to engage novel TAA-expressing cells via a BsAb targeting a linker present on many clinical CAR T-cell therapeutics. We anticipate the use of such adapters could increase CAR T-cell efficacy and reduce potential CAR-associated toxicities.
Role of Blood Pressure Responses to Exercise and Vascular Insulin Sensitivity with Nocturnal Blood Pressure Dipping in Metabolic Syndrome
Authors: Stewart Nathan R. , Heiston Emily M. , Miller Stephanie L. , Ballantyne Anna C. , Cheema Udeyvir S. , Spaeth Andrea M. , Kokkinos Peter , Malin Steven K. 
Published: March 2022

<b><i>Introduction:</i></b> Nocturnal systolic blood pressure (SBP) dipping is independently related to cardiovascular disease risk, but it is unclear if vascular insulin sensitivity associates with SBP dipping in patients with metabolic syndrome (MetS). <b><i>Methods:</i></b> Eighteen adults with MetS (ATP III criteria 3.3 ± 0.6; 53.2 ± 6.5 years; body mass index 35.8 ± 4.5 kg/m<sup>2</sup>) were categorized as “dippers” (≥10% change in SBP; <i>n</i> = 4 F/3 M) or “non-dippers” (&#x3c;10%; <i>n</i> = 9 F/2 M). Twenty-four-hour ambulatory blood pressure was recorded to assess SBP dipping. A euglycemic-hyperinsulinemic clamp (40 mU/m<sup>2</sup>/min, 90 mg/dL) with ultrasound (flow mediated dilation) was performed to test vascular insulin sensitivity. A graded, incremental exercise test was conducted to estimate sympathetic activity. Heart rate (HR) recovery after exercise was then used to determine parasympathetic activity. Metabolic panels and body composition (DXA) were also tested. <b><i>Results:</i></b> Dippers had greater drops in SBP (16.63 ± 5.2 vs. 1.83 ± 5.6%, <i>p</i> &#x3c; 0.01) and experienced an attenuated rise in both SBP<sub>slope</sub> (4.7 ± 2.3 vs. 7.2 ± 2.5 mm Hg/min, <i>p</i> = 0.05) and HR<sub>slope</sub> to the incremental exercise test compared to non-dippers (6.5 ± 0.9 vs. 8.2 ± 1.7 bpm/min, <i>p</i> = 0.03). SBP dipping correlated with higher insulin-stimulated flow-mediated dilation (<i>r</i> = 0.52, <i>p</i> = 0.03), although the relationship was no longer significant after covarying for HR<sub>slope</sub> (<i>r</i> = 0.42, <i>p</i> = 0.09). <b><i>Conclusion:</i></b> Attenuated rises in blood pressure and HR to exercise appear to play a larger role than vascular insulin sensitivity in SBP dipping in adults with MetS.
Cost-Effectiveness of Antihypertensive Deprescribing in Primary Care: a Markov Modelling Study Using Data From the OPTiMISE Trial
Authors: Jowett Sue , Kodabuckus Shahela , Ford Gary A. , Hobbs F.D. Richard , Lown Mark , Mant Jonathan , Payne Rupert , McManus Richard J. , Sheppard James P. ,   for the OPTiMISE investigators
Published: March 2022

Background:
Deprescribing of antihypertensive medications for older patients with normal blood pressure is recommended by some clinical guidelines, where the potential harms of treatment may outweigh the benefits. This study aimed to assess the cost-effectiveness of this approach.

Methods:
A Markov patient-level simulation was undertaken to model the effect of withdrawing one antihypertensive compared with usual care, over a life-time horizon. Model population characteristics were estimated using data from the OPTiMISE antihypertensive deprescribing trial, and the effects of blood pressure changes on outcomes were derived from the literature. Health-related quality of life was modeled in Quality-Adjusted Life Years (QALYs) and presented as costs per QALY gained.

Results:
In the base-case analysis, medication reduction resulted in lower costs than usual care (mean difference £185), but also lower QALYs (mean difference 0.062) per patient over a life-time horizon. Usual care was cost-effective at £2975 per QALY gained (more costly, but more effective). Medication reduction resulted more heart failure and stroke/TIA events but fewer adverse events. Medication reduction may be the preferred strategy at a willingness-to-pay of £20 000/QALY, where the baseline absolute risk of serious drug-related adverse events was ≥7.7% a year (compared with 1.7% in the base-case).

Conclusions:
Although there was uncertainty around many of the assumptions underpinning this model, these findings suggest that antihypertensive medication reduction should not be attempted in many older patients with controlled systolic blood pressure. For populations at high risk of adverse effects, deprescribing may be beneficial, but a targeted approach would be required in routine practice.
Digital Financial Inclusion for Women in the Fourth Industrial Revolution
Authors: Ojo Tinuade Adekunbi 
Published: March 2022

Abstract
Sustainable Development Goal 5 is seen as critical in achieving gender equality. Women and girls are still marginalised and disadvantaged in Africa, and proportionally few are financially and socially independent. Hence, there is a concern about the gender gap in digital financial inclusion on the continent. The paper draws on existing literature to examine the extent to which digital financial inclusion facilitates women’s economic empowerment in four African countries: Ghana, Kenya, Namibia and Lesotho. It further discusses the challenges women face in taking part in the Fourth Industrial Revolution (4IR). Despite all the policies implemented by African states and the growing participation of these nations in 4IR, women still lag behind in digital financial inclusion. The paper concludes that enforcing gender equity in the digital environment is necessary to pave the way for the future. Technology is human-invented and follows the instructions that we dictate. Hence, we could use it to improve gender equality in the 4IR environment and move closer to achieving sustainable development.
A Future of Justice Inclusion: Examining Access to Justice in South Africa through the ‘Ethic of Care’ and ‘Complexity’
Authors: Nagtegaal Jackie , Jooste Yvonne 
Published: March 2022

Abstract
In South Africa, a number of obstructions exist to realising the right to access to justice as enshrined by section 34 of the South African constitution. Globally, many countries grapple with access to justice due to a number of multi-layered and complex causes. This article explores traces, connections, definitions and perceptions related to access to justice so as to allow for a deeper understanding of persisting justice problems. It employs a multi-disciplinary approach that examines worldviews on access to justice in South Africa through the lens of what Sohail Inayatullah terms ‘other ways of knowing’. These worldviews are also considered through the framework of the ‘ethic of care’ as formulated by Carol Gilligan and connected to the notion of ‘complexity’ as understood by Yvonne Malan and Paul Cilliers. The worldviews explored represent ‘different voices’ that discloses a possibility for a future of justice inclusion. The article calls for a people-centred approach to access of justice, underpinned by notions of humility, complexity, concreteness, and particularity.
The Status of Ābirū in Contemporary Iranian Shīʿī Narratives
Authors: Rodziewicz (مجدلينا رودزييفيتش) Magdalena 
Published: March 2022

Abstract
The current study elaborates on the place, status and functions of the concept of ābirū in Shīʿī religious discourse in contemporary Iran. Its main source material has been selected from a variety of rulings (fatwās) and other type of statements delivered by Iranian marājiʿ taqlīd (sources of emulation). By emphasizing the significance of the concept of ābirū in the Iranian tradition and its reception within the Shīʿī tradition, this study outlines the main functions attributed to the idea of ‘good reputation’ and ‘positive social image’ in contemporary Iranian religious jurisprudence. The analysis of the rulings issued by Iranian clergy allows one to distinguish how the idea of ābirū influences verdicts in different aspects of the life of a believer – personal, ethical, legal and political. The study reveals the flexible way in which this moral concept is being incorporated into judgements which, in turn, may result in a novel and nuanced understanding of many Islamic principles, especially in socio-political perspectives.
Exploring the Watch-to-Warning Space: Experimental Outlook Performance during the 2019 Spring Forecasting Experiment in NOAA’s Hazardous Weather Testbed
Authors: Gallo Burkely T. , Wilson Katie A. , Choate Jessica , Knopfmeier Kent , Skinner Patrick , Roberts Brett , Heinselman Pamela , Jirak Israel , Clark Adam J. 
Published: March 2022

Abstract
During the 2019 Spring Forecasting Experiment in NOAA’s Hazardous Weather Testbed, two NWS forecasters issued experimental probabilistic forecasts of hail, tornadoes, and severe convective wind using NSSL’s Warn-on-Forecast System (WoFS). The aim was to explore forecast skill in the time frame between severe convective watches and severe convective warnings during the peak of the spring convective season. Hourly forecasts issued during 2100–0000 UTC, valid from 0100 to 0200 UTC demonstrate how forecasts change with decreasing lead time. Across all 13 cases in this study, the descriptive outlook statistics (e.g., mean outlook area, number of contours) change slightly and the measures of outlook skill (e.g., fractions skill score, reliability) improve incrementally with decreasing lead time. WoFS updraft helicity (UH) probabilities also improve slightly and less consistently with decreasing lead time, though both the WoFS and the forecasters generated skillful forecasts throughout. Larger skill differences with lead time emerge on a case-by-case basis, illustrating cases where forecasters consistently improved upon WoFS guidance, cases where the guidance and the forecasters recognized small-scale features as lead time decreased, and cases where the forecasters issued small areas of high probabilities using guidance and observations. While forecasts generally “honed in” on the reports with slightly smaller contours and higher probabilities, increased confidence could include higher certainty that severe weather would not occur (e.g., lower probabilities). Long-range (1–5 h) WoFS UH probabilities were skillful, and where the guidance erred, forecasters could adjust for those errors and increase their forecasts’ skill as lead time decreased.

Significance Statement
Forecasts are often assumed to improve as an event approaches and uncertainties resolve. This work examines the evolution of experimental forecasts valid over one hour with decreasing lead time issued using the Warn-on-Forecast System (WoFS). Because of its rapidly updating ensemble data assimilation, WoFS can help forecasters understand how thunderstorm hazards may evolve in the next 0–6 h. We found slight improvements in forecast and WoFS performance as a function of lead time over the full experiment; the first forecasts issued and the initial WoFS guidance performed well at long lead times, and good performance continued as the event approached. However, individual cases varied and forecasters frequently combined raw model output with observed mesoscale features to provide skillful small-scale forecasts.
Medicaid Coverage for Podiatric Care: A National Survey
Authors: Brewer Thomas W. , Bonnah Godslove K. , Cairns James S. , Lanese Bethany G. , Waimberg Joshua 
Published: March 2022

Objectives: Medicaid provides health insurance for low-income people meeting specific eligibility requirements. It is funded and administered by both the federal and state governments; this decentralization leads to vastly different programs across the country. The objective of this legal surveillance project was to describe state-by-state differences in podiatric care coverage for nonelderly adults across Medicaid programs. Methods: We used policy surveillance, a form of advanced legal mapping. It is the systematic collection and analysis of written policies across jurisdictions. Policy surveillance captures the important features of law through a rigorous scientific process to turn these policies into structured, quantitative legal data that are suitable for further evaluation or modeling. Data for the 51 jurisdictions were current as of September 1, 2020. Results: The vast majority of jurisdictions (82%) covered podiatric services for all classes of Medicaid beneficiaries, but the rules, restrictions, and limitations around coverage differed. Twenty-five jurisdictions had no limits on the number of podiatric visits during a specified period; 26 jurisdictions indicated a cap. Ten jurisdictions had no explicit limitations on coverage of routine foot care, whereas 33 jurisdictions covered routine foot care only when medically necessary or with a triggering condition. Eight jurisdictions did not cover routine foot care at all, and 28 jurisdictions required prior authorizations. Conclusions: Podiatric care coverage, which is often preventive, varies greatly by state. This variability in coverage, which has not been previously tracked at the level of detail provided in our study, has implications for cost and health outcomes. The value of podiatric care is especially apparent in Medicaid populations. The compilation of these data can serve as a valuable resource for clinicians, researchers, and policy makers.
Comparing forward and reverse transfer from Dutch to German
Authors: Barking Marie , Mos Maria , Backus Ad 
Published: March 2022

Aims and objectives/purpose/research questions: This study compares transfer from Dutch to German by native Dutch speakers who learned German as a second language (forward transfer: L1 to L2) and by native German speakers who are living in the Netherlands (reverse transfer: L2 to L1). The aim of this comparison is to see whether both groups experience the same kind of transfer (i.e., transferring the Dutch preference for prepositional phrases in the postfield position to German) and whether the extent of transfer depends on their language use. Design/methodology/approach: We compiled a corpus (2,908,154 words) consisting of German e-mails written by native Dutch speakers ( n = 21) and native German speakers living in the Netherlands ( n = 9). In addition, speakers filled in the BLP (bilingual language profile) test. Data and analysis: The corpus was analyzed for the speakers’ placement of prepositional phrases, and we linked their answers on the BLP test to their language use in the corpus data. Findings/conclusions: Our data show that the native Dutch speakers use the postfield position more frequently in their German than the native German speakers do. Besides, for both groups, the postfield use was related to the speakers’ use of Dutch as well as German varieties that are influenced by Dutch. Originality: This study directly compares forward and reverse transfer using a large corpus of written German texts, and it links both types of transfer to the speakers’ language use. In doing so, the study shows that the mechanism of entrenchment is likely to underlie transfer in both cases. Significance/implications: The results of this study are in line with a usage-based approach: there is extensive individual variation between speakers regarding their extent of transfer, which partly can be attributed to the speakers’ language use, both in the case of forward and reverse transfer.