bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rationally targeted anti-VISTA antibody that blockades the C-C’ loop region can reverse VISTA immune suppression and remodel the immune microenvironment to potently inhibit tumor growth in an Fc independent manner
Authors: Thakkar Dipti , Paliwal Shalini , Dharmadhikari Bhushan , Guan Siyu , Liu Lillian , Kar Shreya , Tulsian Nikhil K , Gruber Joshua J , DiMascio Leah , Paszkiewicz Konrad H , Ingram Piers J , D Boyd-Kirkup Jerome 
Published: February 2022

BackgroundDespite significant progress in cancer immunotherapy in recent years, resistance to existing immune checkpoint therapies (ICT) is common. V-domain Ig suppressor of T cell activation (VISTA), a predominantly myeloid immune checkpoint regulator, represents a promising therapeutic target due to its role in suppressing proinflammatory antitumor responses in myeloid-enriched tumor microenvironments. However, uncertainty around the cognate VISTA ligand has made the development of effective anti-VISTA antibodies challenging. The expression of VISTA on normal immune cell subtypes argues for a neutralizing non-depleting antibody, however, previous reported anti-VISTA antibodies use IgG1 Fc isotypes that deplete VISTA+ cells by antibody dependent cellular cytotoxicity/complement dependent cytotoxicity and these antibodies have shown fast serum clearance and immune toxicities.MethodHere we used a rational antibody discovery approach to develop the first Fc-independent anti-VISTA antibody, HMBD-002, that binds a computationally predicted functional epitope within the C-C-loop, distinct from other known anti-VISTA antibodies. This epitope is species-conserved allowing robust in vitro and in vivo testing of HMBD-002 in human and murine models of immune activation and cancer including humanized mouse models.ResultsWe demonstrate here that blockade by HMBD-002 inhibits VISTA binding to potential partners, including V-Set and Immunoglobulin domain containing 3, to reduce myeloid-derived suppression of T cell activity and prevent neutrophil migration. Analysis of immune cell milieu suggests that HMBD-002 treatment stimulates a proinflammatory phenotype characterized by a Th1/Th17 response, recapitulating a phenotype previously noted in VISTA knockout models. This mechanism of action is further supported by immune-competent syngenic and humanized mouse models of colorectal, breast and lung cancer where neutralizing VISTA, without depleting VISTA expressing cells, significantly inhibited tumor growth while decreasing infiltration of suppressive myeloid cells and increasing T cell activity. Finally, we did not observe either the fast serum clearance or immune toxicities that have been reported for IgG1 antibodies.ConclusionIn conclusion, we have shown that VISTA-induced immune suppression can be reversed by blockade of the functional C-C’ loop region of VISTA with a first-in-class rationally targeted and non-depleting IgG4 isotype anti-VISTA antibody, HMBD-002. This antibody represents a highly promising novel therapy in the VISTA-suppressed ICT non-responder population.
Soluble PD-L1 as an early marker of progressive disease on nivolumab
Authors: Mahoney Kathleen M , Ross-Macdonald Petra , Yuan Long , Song Linan , Veras Eliseo , Wind-Rotolo Megan , McDermott David F , Stephen Hodi F , Choueiri Toni K , Freeman Gordon J 
Published: February 2022

BackgroundSoluble PD-L1 (sPD-L1) has been associated with worse prognosis in numerous solid tumors. We determined sPD-L1 levels before and during nivolumab treatment in two prospective clinical trials of metastatic clear cell renal cell carcinoma (RCC) and melanoma patients, and investigated its relationship to clinical factors, biomarkers, and outcome.MethodsUsing a new Single Molecule Array assay, serum sPD-L1 level were determined in RCC (CheckMate 009, n=91) and melanoma (CheckMate 038-Part 1, n=78) prior to, and at two time points on treatment. Gene expression data was obtained from biopsies taken prior to, and at day 28 on treatment. Results were integrated with clinical variables, tumor PD-L1 status from immuno-histochemistry, and genomic mutation status.ResultsIn RCC patients, sPD-L1 levels were higher in patients with progressive disease as their best response. For both RCC and melanoma patients, progressive or stable disease was associated with an increase in sPD-L1 on nivolumab therapy, whereas mean sPD-L1 levels did not change or declined in patients with objective responses. By categorizing RCC patients into transcriptomic molecular subtypes, we identified a subgroup where the associations between sPD-L1 and progressive disease were particularly evident. In baseline biopsies, we identified six biological processes that were associated with sPD-L1 level in both RCC and melanoma: higher sPD-L1 is associated with lower tumor expression of the Hallmark gene sets ‘hypoxia’, ‘fatty acid metabolism’, ‘glycolysis’, ‘MTORC1 signaling’ and ‘androgen response’, and with higher expression of ‘KRAS signaling_Down’.ConclusionBaseline and on-therapy sPD-L1 levels in RCC have the potential to predict progressive disease on PD-1 inhibitor nivolumab. In a hypothesis-generating analysis of tumor gene expression, high baseline sPD-L1 is associated with a tumor metabolic state reflecting potentially targetable processes in both melanoma and RCC. In both trials, we observed associations between change in sPD-L1 on treatment and outcome metrics. sPD-L1 levels may further refine a nivolumab-refractory subtype of RCC within transcriptionally based subtypes of RCC.
Reductions in circulating B cell subsets and immunoglobulin G levels with long-term belimumab treatment in patients with SLE
Authors: Struemper Herbert , Kurtinecz Milena , Edwards Lisa , Freimuth William W , Roth David A , Stohl William 
Published: February 2022

ObjectiveTo examine the long-term changes in circulating B cell subsets and IgG levels at 5+ years of continuous belimumab treatment and their correlations with efficacy and safety measures.MethodsThis was a post hoc analysis of a continuation study (BEL112233;NCT00724867) of eligible US patients who completed the 76-week BLISS-76 Study (BEL110751;NCT00410384), with up to eight calendar-years of follow-up and median (IQR) belimumab exposure of 310 (209, 364) weeks. From week 76, patients initially randomised to intravenous belimumab 1 mg/kg or 10 mg/kg every 4 weeks in BLISS-76 continued to receive the same dose in the continuation study, while those initially randomised to placebo received belimumab 10 mg/kg intravenous every 4 weeks during continuation. All patients continued to receive standard SLE therapy. Biomarker data were collected, and the effects on baseline and early changes (weeks 0–24 after starting belimumab) from baseline in biomarkers on SLE Responder Index (SRI-4) and infection rate were evaluated.ResultsOf the 819 patients from BLISS-76, 268 self-selecting patients entered BEL112233. Compared with baseline, B cell subset counts decreased by 40%–99% after 312 weeks (6 years), and serum IgG levels decreased by 28% after 284 weeks. Higher baseline naïve B cell counts were associated with greater SRI-4 response rates (p<0.05), whereas higher baseline SLE subset plasma and short-lived plasma B cell counts were associated with lower SRI-4 response rates (p<0.05). Elevated baseline IgG levels were associated with increased infection rates over the treatment period (p<0.05), and early greater decreases in IgG levels were associated with higher SRI-4 response rates (p<0.05).ConclusionsBelimumab treatment up to 312 weeks (6 years) resulted in substantial decreases in several circulating B cell subsets and IgG levels. Higher baseline naïve B cell counts and IgG levels were associated with improved SRI-4 response and increased infection rates, respectively.
Safety, patient acceptance and diagnostic accuracy of ultrasound core needle biopsy of parotid or submandibular glands in primary Sjögren’s syndrome with suspected salivary gland lymphoma
Authors: Giovannini Ivan , Lorenzon Michele , Manfrè Valeria , Zandonella Callegher Sara , Pegolo Enrico , Zuiani Chiara , Girometti Rossano , Hocevar Alojzija , Dejaco Christian , Quartuccio Luca , De Vita Salvatore , Zabotti Alen 
Published: February 2022

BackgroundEnlargement of the major salivary glands (SGs) is a major risk factor for B-cell lymphoma among patients with primary Sjögren’s syndrome (pSS). Ultrasound-guided core needle biopsy (US-guided CNB) could be a novel technique to manage SG enlargement among patients with pSS.ObjectiveAccordingly, this study’s main aim was to evaluate the safety, patient tolerance and diagnostic accuracy of US-guided CNB procedure for patients with pSS with major SG enlargement.MethodsPatients with clinical diagnosis of pSS and a clinical indication for SG biopsy consecutively underwent US-guided CNB between September 2019 and June 2021. These patients were evaluated clinically 1, 2 and 12 weeks after US-guided CNB. Patients were asked to complete a questionnaire about postprocedural complications as well as periprocedural pain, using the Visual Analogue Scale. Complications were categorised as transient (<12 weeks) or persistent (≥12 weeks).ResultsUS-guided CNB was performed on 30 major salivary glands (22 parotid glands and 8 submandibular glands). The procedure was well tolerated. Transient complications—such as haematoma, swelling—were observed among 43% of patients, and mean periprocedural pain was low. However, no persistent complications were reported during the study’s follow-up period.ConclusionUS-guided CNB represents a novel approach for the management of patients with pSS with SG enlargement. The procedure showed remarkable patient safety and tolerance, allowing adequate glandular sampling and a definite diagnosis for almost all participating patients without long-term complications.
Bermudan option pricing by quantum amplitude estimation and Chebyshev interpolation
Authors: Miyamoto Koichi 
Published: February 2022

AbstractPricing of financial derivatives, in particular early exercisable options such as Bermudan options, is an important but heavy numerical task in financial institutions, and its speed-up will provide a large business impact. Recently, applications of quantum computing to financial problems have been started to be investigated. In this paper, we first propose a quantum algorithm for Bermudan option pricing. This method performs the approximation of the continuation value, which is a crucial part of Bermudan option pricing, by Chebyshev interpolation, using the values at interpolation nodes estimated by quantum amplitude estimation. In this method, the number of calls to the oracle to generate underlying asset price paths scales as $\widetilde{O}(\epsilon ^{-1})$

O
˜

(

ϵ

−
1

)
, where ϵ is the error tolerance of the option price. This means the quadratic speed-up compared with classical Monte Carlo-based methods such as least-squares Monte Carlo, in which the oracle call number is $\widetilde{O}(\epsilon ^{-2})$

O
˜

(

ϵ

−
2

)
.
Structural reflection, shrewd cardinals and the size of the continuum
Authors: Lücke Philipp 
Published: February 2022

Motivated by results of Bagaria, Magidor and Väänänen, we study characterizations of large cardinal properties through reflection principles for classes of structures. More specifically, we aim to characterize notions from the lower end of the large cardinal hierarchy through the principle [Formula: see text] introduced by Bagaria and Väänänen. Our results isolate a narrow interval in the large cardinal hierarchy that is bounded from below by total indescribability and from above by subtleness, and contains all large cardinals that can be characterized through the validity of the principle [Formula: see text] for all classes of structures defined by formulas in a fixed level of the Lévy hierarchy. Moreover, it turns out that no property that can be characterized through this principle can provably imply strong inaccessibility. The proofs of these results rely heavily on the notion of shrewd cardinals, introduced by Rathjen in a proof-theoretic context, and embedding characterizations of these cardinals that resembles Magidor’s classical characterization of supercompactness. In addition, we show that several important weak large cardinal properties, like weak inaccessibility, weak Mahloness or weak [Formula: see text]-indescribability, can be canonically characterized through localized versions of the principle [Formula: see text]. Finally, the techniques developed in the proofs of these characterizations also allow us to show that Hamkin’s weakly compact embedding property is equivalent to Lévy’s notion of weak [Formula: see text]-indescribability.
Linking a Trio of Molecular Features in Clear-Cell Renal Cell Carcinoma
Authors: Labaki Chris , Van Allen Eliezer M. , Choueiri Toni K. 
Published: February 2022

Clear-cell renal cell carcinoma exhibits unique molecular features, some of which are associated with the response to immunotherapy. However, the interactions between different genomic entities remains incompletely understood. In this issue, Zhou and colleagues show that PBRM1 inactivation is associated with increased expression of specific human endogenous retroviruses and identify HIF1/2A transcriptional activity as an important mediator of this interaction, helping uncover the interplay between some of the key molecular traits of this disease.See related article by Zhou et al., p. 285 (3).
Seasonality effect on ant (Hymenoptera: Formicidae) activity in an ecotonal environment in the state of Piauí, Brazil
Authors: Miranda Vinícius Lima de , Koch Elmo Borges de Azevedo , Oliveira Laine da Silva , Nunes Joanes de Jesus Moreira , Barbosa Diogo Brunno e Silva , Soares Maria Regiane Araujo , Mariano Cléa dos Santos Ferreira , Delabie Jacques Hubert Charles 
Published: February 2022

This study aimed to compare the activity of ants during the rainy and dry seasons in a transitional environment (ecotone) at the interface of Cerrado and Caatinga biomes situated in the state of Piauí, where studies of local ant fauna are still incipient. The research was carried out at Floriano, state of Piauí, Brazil. Ants were sampled during the rainy season in December 2018 and during the dry season in June 2019. Three parallel transects were established at least 100 m apart. At each point, three sampling methods were used, with attractive baits placed on the trees and ground, and pitfall traps on the ground. Thirty-one ant species belonging to 14 genera and five subfamilies were collected, with 27 recorded in the rainy season and 17 in the dry season. The only species reported with the three collection methods and the two seasons was Camponotus crassus Mayr, 1862. Seven ant species sampled in this study are new reports for the state of Piauí. There was a significant difference in the average number of ants and the composition of the assemblages between the rainy and dry seasons. We demonstrate that the activity of ants is influenced by seasonality, corroborating our hypotheses. This is only the second study on ant diversity in the state of Piauí, and more studies are necessary to understand the processes and factors which regulate the activity patterns of ants in ecotonal situations like those observed in this region.
Quando a estética realista se torna simbólica: O Jardim de Cerejeiras de Peter Brook (1981)
Authors: Ortiz Sergio Ricardo Lessa 
Published: February 2022

Este artigo aborda questões sobre o processo concepção dos elementos visuais do espetáculo O Jardim das Cerejeiras de Peter Brook. Destaca sobretudo a compreensão sobre o impacto do simbólico pensado para os cenários do espetáculo sobre os trajes de cena elaborados por Chloé Obolensky, cenógrafa que estreou com essa montagem no Centro Internacional de Pesquisa Teatral em 1981.
Advancing Near-Real-Time Quality Controls of Meteorological Observations
Authors: Toreti Andrea , Bratu Marian , Müller Evelyn , van der Grijn Gerald , Oliveira Igor , Zampieri Matteo , Ceglar Andrej 
Published: February 2022

Abstract
Meteorological observations from ground weather stations are of the upmost importance to implement and run sectoral climate services and to perform scientific activities, such as models’ evaluation and data assimilation. However, meteorological observations may be affected by errors deteriorating the quality and the reliability of the products based on these data. To avoid such a cascade of effects, it is essential to quality check meteorological observations in near–real time. A new system based on several levels of increasing complexity checks is proposed here. Besides the standard quality controls, this system applies dynamic and adaptive checks targeting exactly the locations and the data under analysis. The proposed system is designed to be flexible and easily modifiable thanks to its combined R and XML implementation. To facilitate its applicability, the proposed system is made available as a free open-source software: QuackMe.
The Simulated Atmospheric Response to Western North Pacific Sea Surface Temperature Anomalies
Authors: Yook Simchan , Thompson David W. J. , Sun Lantao , Patrizio Casey 
Published: February 2022

Abstract
Observations reveal two distinct patterns of atmospheric variability associated with wintertime variations in midlatitude sea surface temperatures (SSTs) in the North Pacific sector: 1) a pattern of atmospheric circulation anomalies that peaks 2–3 weeks prior to large SST anomalies in the western North Pacific that is consistent with “atmospheric forcing” of the SST field, and 2) a pattern that lags SST anomalies in the western North Pacific by several weeks that is consistent with the “atmospheric response” to the SST field. Here we explore analogous lead–lag relations between the atmospheric circulation and western North Pacific SST anomalies in two sets of simulations run on the NCAR Community Earth System Model version 1 (CESM1): 1) a simulation run on a fully coupled version of CESM1 and 2) a simulation forced with prescribed, time-evolving SST anomalies over the western North Pacific region. Together, the simulations support the interpretation that the observed lead–lag relationships between western North Pacific SST anomalies and the atmospheric circulation reveal the patterns of atmospheric variability that both force and respond to midlatitude SST anomalies. The results provide numerical evidence that SST variability over the western North Pacific has a demonstrable effect on the large-scale atmospheric circulation throughout the North Pacific sector.
Epidemiology of Hospital Admissions for Craniosynostosis in Australia: A Population-Based Study
Authors: Junaid Mohammed , Slack-Smith Linda , Wong Kingsley , Baynam Gareth , Calache Hanny , Hewitt Timothy , Leonard Helen 
Published: February 2022

To describe trends, age, and sex-specific patterns of population hospital admissions with a diagnosis of craniosynostosis (CS) in Australia. Population data for hospital separations (in-patient) from public and private hospitals (July 1996-June 2018) were obtained from the publicly available Australian Institute of Health and Welfare (AIHW) National Hospital Morbidity Database. The outcome variables were hospital separation rates (HSR) (number of hospital separations divided by the estimated resident population [ERP] per year) and average length of stay (aLOS) (patient days divided by the number of hospital separations) with a diagnosis of CS. Trends in HSR and aLOS adjusted for age, sex, and type of CS were investigated by negative binomial regression presented as annual percent change (APC). In 8057 admissions identified, we observed no significant change in the annual trend for HSR for the 22-year period. However, a marginal annual decrease of 1.6% (95% CI: -0.7, -2.4) in the aLOS was identified for the same time period. HSR were higher for males, infants, and single suture synostosis. aLOS was 3.8 days (95% CI: 3.8, 3.9) per visit, longer for syndromic conditions. There was a minor reduction in the average length of hospital stay for CS over the 22-year period potentially indicative of improved care. Population-level information on hospitalisations for rare craniofacial conditions can inform research, clinical, and surgical practice.
Corneal scarring following collagen cross-linking: evidence of increased lysyl oxidase activity
Authors: Shah Sushmita G , Shetty Rohit , Ghosh Arkasubra , Shah Gaurav Y 
Published: February 2022

Purpose To report a case of corneal scarring following collagen cross linking in a young female. Methods A 24-year-old female presented to us with complaints of decreased vision and a white spot in her left eye following collagen cross linking (CXL) performed elsewhere, four years prior. We diagnosed her as a case of left eye leucomatous corneal opacity for which she underwent optical penetrating keratoplasty under local anaesthesia. The excised corneal tissue was evaluated by routine histopathology and immunohistochemistry. Results At the final follow up visit, one year following corneal transplantation, her visual acuity improved to 20/20, J1 with a clear graft. Conclusion Vision threatening corneal scarring may be rarely noted following CXL.
Isolated CNS Sarcoidosis Versus Systemic Sarcoidosis With CNS Involvement: A Same Disease?
Authors: Courtin E. , Ouallet JC. , Lazaro E. , Martin-Negrier M-L. , Cohen-Aubart F. , Duffau P. 
Published: February 2022

Neurological involvement occurs in 5 to 15% of patients with sarcoidosis. It rarely represents the sole manifestation of the disease, a condition called isolated neurosarcoidosis. Objectives: To describe patients with definite isolated central neurosarcoidosis. To compare their characteristics to a group of systemic sarcoidosis with central neurologic involvement. Methods: Monocentric retrospective study of all patients presenting with central neurosarcoidosis (NS) over a 10 year period, subsequently divided into 2 groups: isolated neurosarcoidosis (INS) and systemic neurosarcoidosis (SNS). Results: We report 10 cases of INS and subsequently, we compared their characteristics to a group of 30 patients with SNS. INS patients exhibited brain parenchymal involvement (8/10), meningeal disease (8/10), myelitis (3/10), cranial neuropathy (3/10), neuroendocrine impairment (1/10). Cerebro-spinal fluid (CSF) analysis was conducted in 8/10 patients and showed pleocytosis in 6/8 (75%), elevated protein level in (4/8) 50%, oligoclonal intrathecal synthesis in 1/5 (20%). All patients received steroids, 7/10 (70%) required associated immunosuppressive therapy, 5 of which TNFα inhibitors. When compared to patients with SNS, INS patients were more likely to experience seizures (60% vs 23.3%); display encephalic parenchymal enhancing lesions (80% vs 39.3%) or encephalic leptomeningeal involvement (80% vs 35.7%). Serum angiotensin converting enzyme (ACE) was elevated in a third of patients with SNS but none of those with INS. Conclusion: The phenotypes of patients with INS are similar to the ones described in SNS. Serum ACE should not be regarded as a diagnostic test in patients with isolated neurosarcoidosis but could be useful in detecting subclinical extra neurologic involvement during follow up.