bluuebunny/crossref_metadata_2025_split huggingface dataset:
Restoration of T-cell Effector Function, Depletion of Tregs, and Direct Killing of Tumor Cells: The Multiple Mechanisms of Action of a-TIGIT Antagonist Antibodies
Authors: Preillon Julie , Cuende Julia , Rabolli Virginie , Garnero Lucile , Mercier Marjorie , Wald Noémie , Pappalardo Angela , Denies Sofie , Jamart Diane , Michaux Anne-Catherine , Pirson Romain , Pitard Vincent , Bagot Martine , Prasad Shruthi , Houthuys Erica , Brouwer Margreet , Marillier Reece , Lambolez Florence , Marchante Joäo R. , Nyawouame Florence , Carter Mathew J. , Baron-Bodo Véronique , Marie-Cardine Anne , Cragg Mark , Déchanet-Merville Julie , Driessens Gregory , Hoofd Catherine 
Published: December 2020

Abstract
TIGIT is an immune checkpoint inhibitor expressed by effector CD4+ and CD8+ T cells, NK cells, and regulatory T cells (Tregs). Inhibition of TIGIT-ligand binding using antagonistic anti-TIGIT mAbs has shown in vitro potential to restore T-cell function and therapeutic efficacy in murine tumor models when combined with an anti–PD(L)-1 antibody. In the current work, we demonstrate broader TIGIT expression than previously reported in healthy donors and patients with cancer with expression on γδ T cells, particularly in CMV-seropositive donors, and on tumor cells from hematologic malignancies. Quantification of TIGIT density revealed tumor-infiltrating Tregs as the population expressing the highest receptor density. Consequently, the therapeutic potential of anti-TIGIT mAbs might be wider than the previously described anti–PD(L)-1-like restoration of αβ T-cell function. CD155 also mediated inhibition of γδ T cells, an immune population not previously described to be sensitive to TIGIT inhibition, which could be fully prevented via use of an antagonistic anti-TIGIT mAb (EOS-448). In PBMCs from patients with cancer, as well as in tumor-infiltrating lymphocytes from mice, the higher TIGIT expression in Tregs correlated with strong antibody-dependent killing and preferential depletion of this highly immunosuppressive population. Accordingly, the ADCC/ADCP–enabling format of the anti-TIGIT mAb had superior antitumor activity, which was dependent upon Fcγ receptor engagement. In addition, the anti-TIGIT mAb was able to induce direct killing of TIGIT-expressing tumor cells both in human patient material and in animal models, providing strong rationale for therapeutic intervention in hematologic malignancies. These findings reveal multiple therapeutic opportunities for anti-TIGIT mAbs in cancer therapeutics.
Decidual-Like NK Cell Polarization: From Cancer Killing to Cancer Nurturing
Authors: Albini Adriana , Noonan Douglas M. 
Published: December 2020

Abstract

Summary:
Natural killer (NK) cells accumulate at the fetal–maternal interface and represent 70% of immune cells in the decidua (dNK) at first-trimester pregnancy; they are immune-tolerant toward the semiallogenic fetus and are “nurturing” and nonkilling NK cells. A subset of NK cells in patients with cancer have features in common with dNK, which include expressing CD56, CD9, CD49a, and CXCR3, being poorly cytotoxic and proangiogenic, and mimicking the decidual nurturing role. In the oncologic patient, several factors can “decidualize” NK cells, turning them into immune-suppressant, growth-promoting proangiogenic cells. Here, we suggest ways to sharpen their blunted blades and intercept and curb their cancer-nurturing attitudes to restore their cytotoxic capabilities.
Investigating the division of scientific labor using the Contributor Roles Taxonomy (CRediT)
Authors: Larivière Vincent , Pontille David , Sugimoto Cassidy R. 
Published: December 2020

AbstractContributorship statements were introduced by scholarly journals in the late 1990s to provide more details on the specific contributions made by authors to research papers. After more than a decade of idiosyncratic taxonomies by journals, a partnership between medical journals and standards organizations has led to the establishment, in 2015, of the Contributor Roles Taxonomy (CRediT), which provides a standardized set of 14 research contributions. Using the data from Public Library of Science (PLOS) journals over the 2017–2018 period (N = 30,054 papers), this paper analyzes how research contributions are divided across research teams, focusing on the association between division of labor and number of authors, and authors’ position and specific contributions. It also assesses whether some contributions are more likely to be performed in conjunction with others and examines how the new taxonomy provides greater insight into the gendered nature of labor division. The paper concludes with a discussion of results with respect to current issues in research evaluation, science policy, and responsible research practices.
World Cinema Will not Work
Authors: Brown William 
Published: December 2020

Abstract
In this essay, I engage with the concept of ‘world cinema,’ identifying ways in which the term ‘world’ might always already come loaded with masculine and, in particular, white connotations, such that a turn to ‘world cinema’ runs the risk of reaffirming the centrality of masculinity and whiteness—at a time when, perhaps it is of utmost importance, for the sake of the continuation of human and other life, to challenge and perhaps even to negate that centrality. What applies to ‘world’ (which may be a shorthand for white masculinity) may also apply to cinema, and so it is that cinema and white masculinity alike that must be abandoned for human life on Earth to progress. To propose a turn to world cinema may thus not ‘work’ as a means to develop film studies in an ethical, more inclusive direction, since both world and cinema are by nature exclusive, rather than inclusive.
Numerical Simulation of Mountain Waves over the Southern Andes. Part I: Mountain Wave and Secondary Wave Character, Evolutions, and Breaking
Authors: Lund Thomas S. , Fritts David C. , Wan Kam , Laughman Brian , Liu Han-Li 
Published: December 2020

AbstractThis paper addresses the compressible nonlinear dynamics accompanying increasing mountain wave (MW) forcing over the southern Andes and propagation into the mesosphere and lower thermosphere (MLT) under winter conditions. A stretched grid provides very high resolution of the MW dynamics in a large computational domain. A slow increase of cross-mountain winds enables MWs to initially break in the mesosphere and extend to lower and higher altitudes thereafter. MW structure and breaking is strongly modulated by static mean and semidiurnal tide fields exhibiting a critical level at ~114 km for zonal MW propagation. Varying vertical group velocities for different zonal wavelengthsλxyield initial breaking in the lee of the major Andes peaks forλx~ 50 km, and extending significantly upstream for largerλxapproaching the critical level at later times. The localized extent of the Andes terrain in latitude leads to “ship wave” responses above the individual peaks at earlier times, and a much larger ship-wave response at 100 km and above as the larger-scale MWs achieve large amplitudes. Other responses above regions of MW breaking include large-scale secondary gravity waves and acoustic waves that achieve very large amplitudes extending well into the thermosphere. MW breaking also causes momentum deposition that yields local decelerations initially, which merge and extend horizontally thereafter and persist throughout the event. Companion papers examine the associated momentum fluxes, mean-flow evolution, gravity wave–tidal interactions, and the MW instability dynamics and sources of secondary gravity waves and acoustic waves.
A Simultaneous Multiscale Data Assimilation Using Scale-Dependent Localization in GSI-Based Hybrid 4DEnVar for NCEP FV3-Based GFS
Authors: Huang Bo , Wang Xuguang , Kleist Daryl T. , Lei Ting 
Published: December 2020

AbstractA scale-dependent localization (SDL) method was formulated and implemented in the Gridpoint Statistical Interpolation (GSI)-based four-dimensional ensemble-variational (4DEnVar) system for NCEP FV3-based Global Forecast System (GFS). SDL applies different localization to different scales of ensemble covariances, while performing a single-step simultaneous assimilation of all available observations. Two SDL variants with (SDL-Cross) and without (SDL-NoCross) considering cross-wave-band covariances were examined. The performance of two- and three-wave-band SDL experiments (W2 and W3, respectively) was evaluated through 1-month cycled data assimilation experiments. SDL improves global forecasts to 5 days over scale-invariant localization including the operationally tuned level-dependent scale-invariant localization (W1-Ope). The W3 SDL-Cross experiment shows more accurate tropical storm–track forecasts at shorter lead times than W1-Ope. Compared to the W2 SDL experiments, the W3 SDL counterparts applying tighter horizontal localization at medium-scale wave band generally show improved global forecasts below 100 hPa, but degraded global forecasts above 50 hPa. While the outperformance of the W3 SDL-NoCross experiment versus the W2 SDL-NoCross experiment below 100 hPa lasts for 5 days, that of the W3 SDL-Cross experiment versus the W2 SDL-Cross experiment lasts for 3 days. Due to local spatial averaging of ensemble covariances that may alleviate sampling error, the SDL-NoCross experiments show slightly better forecasts than the SDL-Cross experiments at shorter lead times. However, the SDL-Cross experiments outperform the SDL-NoCross experiments at longer lead times, likely from retention of more heterogeneity of ensemble covariances and resultant analyses with improved balance. Relative performance of tropical storm–track forecasts in the W2 and W3 SDL experiments are generally consistent with that of global forecasts.
Institution-Specific Strategies for Head and Neck Oncology Triage During the COVID-19 Pandemic
Authors: Freeman Michael H. , Shinn Justin R. , Langerman Alexander 
Published: December 2020

Background: This work seeks to better understand the triage strategies employed by head and neck oncologic surgical divisions during the initial phases of the coronavirus 2019 (COVID-19) outbreak. Methods: Thirty-six American head and neck surgical oncology practices responded to questions regarding the triage strategies employed from March to May 2020. Results: Of the programs surveyed, 11 (31%) had official department or hospital-specific guidelines for mitigating care delays and determining which surgical cases could proceed. Seventeen (47%) programs left the decision to proceed with surgery to individual surgeon discretion. Five (14%) programs employed committee review, and 7 (19%) used chairman review systems to grant permission for surgery. Every program surveyed, including multiple in COVID-19 outbreak epicenters, continued to perform complex head and neck cancer resections with free flap reconstruction. Conclusions: During the initial phases of the COVID-19 pandemic experience in the United States, head and neck surgical oncology divisions largely eschewed formal triage policies and favored practices that allowed individual surgeons discretion in the decision whether or not to operate. Better understanding the shortcomings of such an approach could help mitigate care delays and improve oncologic outcomes during future outbreaks of COVID-19 and other resource-limiting events. Level of Evidence: 4.
The brooding omnipresence of Carl Schmitt in contemporary jurisprudence: Reflections on William Scheuerman’s The End of Law: Carl Schmitt in the 21st century
Authors: Levinson Sanford 
Published: December 2020

Carl Schmitt, whatever his clear deficiencies as a human being and excesses in his overall thought, is, by any objective measure, one of the leading jurisprudential figures of the 20th century. And the questions he raised – about the inevitably of discretionary decision-making in the age of the modern administrative state; the breakdown of liberal parliamentarism; or the importance of that ‘emergencies’ must play in any cogent jurisprudential theory, to name only three – continue to resonate very much into the 21st century. William Scheuerman is at best ambivalent, if not hostile, to many aspects of Schmitt and Schmittian theory, but he presents Schmitt’s ideas with remarkable clarity that enables the reader to understand why it continues to be important to read and to wrestle with him.
Peritoneal dialysis in critically ill children in resource-limited setting: A prospective cohort study
Authors: Choudhary Pallavi , Kumar Virendra , Saha Abhijeet , Thakur Archana 
Published: December 2020

Background: Peritoneal dialysis (PD) is easily available and simple lifesaving procedure in children with renal impairment. There is paucity of reports on efficacy of PD in critically ill children in presence of shock and those requiring mechanical ventilation. Methods: In this prospective observational study, efficacy and outcome of PD were evaluated in 50 critically ill children aged 1 month to 14 years admitted in pediatric intensive care unit of a tertiary care teaching hospital in India. Results: Indication of PD was acute kidney injury (AKI) in 66% of patients followed by chronic kidney disease with acute deterioration due to infectious complications in 34%. Bacterial sepsis was the most common cause of AKI (22%), others being malaria (14%) and severe dengue (12%). At initiation of PD, 26% of patients were in shock and 46% were mechanically ventilated. PD was effective and improvement in pH, bicarbonate, and lactate started within hours, with consistent improvement in estimated glomerular filtration rate by 24 h, which continued till the end of procedure, including the subgroup of patients with shock and mechanical ventilation. Total complications were seen in 14% and of which peritonitis was present in 4.0% of patients. Mortality was seen in 14% (7/50) of patients. Shock at initiation of PD (odds ratio (OR), 5.03; 95% confidence interval (CI), 0.95–26.69; p < 0.04) and requirement of mechanical ventilation (OR, 9.17; 95% CI, 1.01–83.10; p < 0.02) were associated with mortality. Conclusions: Acute PD in critically ill children with renal impairment is a lifesaving procedure. Treatment of shock with resuscitative measures and respiratory failure with mechanical ventilation, along with PD, resulted in favorable renal outcome.
Clinical characteristics associated with the properties of gut microbiota in peritoneal dialysis patients
Authors: Jiang Na , Zhang Chenhong , Feng Hao , Yuan Jiangzi , Ding Li , Fang Wei , Gu Aiping , Huang Jiaying , Li Na , Gu Leyi , Ni Zhaohui , Mou Shan 
Published: December 2020

Background: Gut microbiota alters in patients with end-stage renal disease, which contributes to inflammation, atherosclerosis, and results in increased incidence of cardiovascular diseases. The present study investigated the potential clinical factors, which influence the gut microbial structure and function in patients undergoing peritoneal dialysis (PD). Methods: This is a cross-sectional study performed in 81 prevalent PD patients. Gut microbiota was assessed by high throughput sequencing of 16S ribosomal ribonucleic acid gene in fecal samples. Gas chromatography was conducted to measure stool short-chain fat acid (SCFA) concentrations. Demographic parameters and clinical characteristics, including dialysis regimen, residual renal function, nutrition, and inflammation, were retrieved and related to the properties of gut microbiota. Results: PD duration, peritoneal glucose exposure, and estimated glomerulus filtration rate (eGFR) were identified to be associated with microbial variations. Significant separation of microbial composition was shown between patients with short or long PD duration ( p = 0.015) and marginal differences were found between patients grouped by different levels of peritoneal glucose exposure ( p = 0.056) or residual renal function ( p = 0.063). A couple of gut bacteria showed different abundance at amplicon sequencing variant level between these patient groups ( p < 0.05). In addition, stool isobutyric and isovaleric acid concentrations were significantly reduced in patients with longer dialysis duration, higher peritoneal glucose exposure, or declined eGFR ( p < 0.05). Conclusions: This pilot study demonstrated that long dialysis duration, high peritoneal glucose exposure, and loss of residual renal function were associated with gut microbiota alteration and reduced branched-chain SCFA production in PD patients.
A Case Report on Congenital Hyperinsulinism
Authors: Pagdar Sandip , Jobanputra Kunj , Sahni Mohit 
Published: December 2020

Introduction: Congenital hyperinsulinism (CH) is the most common reason for persistent hypoglycemia in neonates. Insulin levels increased inappropriately in the presence of hypoglycemia. Initial management is nonsurgical, but if it fails then partial pancreatectomy is done, which is a surgical procedure. Objective: To report newborn with CH and update medical and/or surgical treatment. Case report: It is reporting of a term newborn with severe symptomatic hypoglycemia not responding to medical treatment. Gene study was done—ABCC8 gene has been identified as homozygous deletion of exon 13 and parents ger08Y—showing heterozygous deletion of exon 13. Genetic study was consistent with focal CH. Discussion: This report presents diagnosis and clinical features of CH.
Bronchial arterial embolization may reduce the risk of severe bleeding in central airway obstruction due to renal cell carcinomas during bronchoscopic procedures
Authors: Tao Meimei , Zhang Nan , Wang Hongwu , Ma Hongming , Gao Hong , Wang Zhina 
Published: December 2020

Background: Hemorrhage is a life-threatening complication during bronchoscopic intervention in patients with central airway obstruction (CAO) due to metastatic renal cell carcinoma (RCC). Whether pre-bronchoscopic bronchial arterial embolization (BAE) can reduce the risk of severe bleeding in CAO patients due to metastatic RCC remains unclear. Methods: A total of 31 CAO patients due to metastatic RCC were included retrospectively and divided into a BAE group (receiving pre-bronchoscopic BAE) and non-BAE group in this study. Based on computed tomography (CT) and bronchoscopic findings, tumor debulking was used to reconstruct the airway during interventional bronchoscopy. The primary outcome was the incidence of severe bleeding during bronchoscopic procedures. Bleeding-related complications, Karnofsky performance score (KPS) and dyspnea score were also analyzed over a 1-month observation period. Results: There were no significant differences between the two groups in baseline characteristics, including patients’ features, tumor morphology under CT scannings, tumor site, and obstruction degree under bronchoscopic examination. Procedure-related bleeding occurred in all 31 patients. Pre-bronchoscopic BAE significantly reduced the incidence of moderate and major bleeding when compared with that in the non-BAE group. The incidence of poor visualization and hypoxia was also reduced significantly in the BAE group. There was no significant difference in KPS and dyspnea score between the BAE and non-BAE groups at 1 month follow up. Conclusion: Pre-bronchoscopic BAE might be a feasible option to reduce the risk of severe bleeding for CAO patients due to metastatic RCC during bronchoscopic intervention. Interventional bronchoscopy was a safe and effective procedure for CAO due to metastatic RCC. The reviews of this paper are available via the supplemental material section.
Targeting the eCIRP/TREM-1 interaction with a small molecule inhibitor improves cardiac dysfunction in neonatal sepsis
Authors: Denning Naomi-Liza , Aziz Monowar , Diao Li , Prince Jose M. , Wang Ping 
Published: December 2020

AbstractBackgroundNeonatal sepsis and the associated myocardial dysfunction remain a leading cause of infant mortality. Extracellular cold-inducible RNA-binding protein (eCIRP) acts as a ligand of triggering receptor expressed on myeloid cells-1 (TREM-1). M3 is a small CIRP-derived peptide that inhibits the eCIRP/TREM-1 interaction. We hypothesize that the eCIRP/TREM-1 interaction in cardiomyocytes contributes to sepsis-induced cardiac dysfunction in neonatal sepsis, while M3 is cardioprotective.MethodsSerum was collected from neonates in the Neonatal Intensive Care Unit (NICU). 5–7-day old C57BL/6 mouse pups were used in this study. Primary murine neonatal cardiomyocytes were stimulated with recombinant murine (rm) CIRP with M3. TREM-1 mRNA and supernatant cytokine levels were assayed. Mitochondrial oxidative stress, ROS, and membrane potential were assayed. Neonatal mice were injected with rmCIRP and speckle-tracking echocardiography was conducted to measure cardiac strain. Sepsis was induced byi.p.cecal slurry. Mouse pups were treated with M3 or vehicle. After 16 h, echocardiography was performed followed by euthanasia for tissue analysis. A 7-day survival study was conducted.ResultsSerum eCIRP levels were elevated in septic human neonates. rmCIRP stimulation of cardiomyocytes increased TREM-1 gene expression. Stimulation of cardiomyocytes with rmCIRP upregulated TNF-α and IL-6 in the supernatants, while this upregulation was inhibited by M3. Stimulation of cardiomyocytes with rmCIRP resulted in a reduction in mitochondrial membrane potential (MMP) while M3 treatment returned MMP to near baseline. rmCIRP caused mitochondrial calcium overload; this was inhibited by M3. rmCIRP injection impaired longitudinal and radial cardiac strain. Sepsis resulted in cardiac dysfunction with a reduction in cardiac output and left ventricular end diastolic diameter. Both were improved by M3 treatment. Treatment with M3 attenuated serum, cardiac, and pulmonary levels of pro-inflammatory cytokines compared to vehicle-treated septic neonates. M3 dramatically increased sepsis survival.ConclusionsInhibition of eCIRP/TREM-1 interaction with M3 is cardioprotective, decreases inflammation, and improves survival in neonatal sepsis.Trial registrationRetrospectively registered.
Metabotropic glutamate receptor 5 regulates synaptic plasticity in a chronic migraine rat model through the PKC/NR2B signal
Authors: Niu Yingying , Zeng Xiaoxu , Zhao Lilin , Zhou Yang , Qin Guangcheng , Zhang Dunke , Fu Qingqing , Zhou Jiying , Chen Lixue 
Published: December 2020

Abstract
Background
The mechanism of chronic migraine (CM) is complex, central sensitization is considered as one of the pathological mechanism. Synaptic plasticity is the basis of central sensitization. Metabotropic glutamate receptor 5 (mGluR5) plays a vital role in the synaptic plasticity of the central nervous system. However, whether mGluR5 can promote the central sensitization by regulating synaptic plasticity in CM is unknown.

Methods
Male Wistar rats were used to establish a CM rat model, and the expression of mGluR5 mRNA and protein were detected by qRT-PCR and western blot. The allodynia was assessed by mechanical and thermal thresholds, and central sensitization was assessed by expression of the phosphorylation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) at Serine 133(pCREB-S133) and c-Fos. The synaptic-associated protein postsynaptic density protein 95 (PSD), synaptophysin (Syp), and synaptophysin-1(Syt-1), synaptic ultrastructure, and dendritic spines were detected to explore synaptic plasticity. The expression of PKC, total NR2B(tNR2B), and phosphorylation of NR2B at Tyr1472(pNR2B-Y1472) were detected by western blot.

Results
We found that the expression of mGluR5 was upregulated in CM rats. Downregulated the mGluR5 with MPEP alleviated the allodynia and reduced the expression of CGRP, pCREB-S133, c-Fos, PSD, Syp and Syt-1 and synaptic transmission. Moreover, the administration of MPEP inhibited the upregulation of PKC and pNR2B-Y1472.

Conclusions
These results indicate that mGluR5 contributes to central sensitization by regulating synaptic plasticity in CM through the PKC/NR2B signal, which suggests that mGluR5 may be a potential therapeutic candidate for CM.