bluuebunny/crossref_metadata_2025_split huggingface dataset:
LRIG2 promotes glioblastoma progression by modulating innate antitumor immunity through macrophage infiltration and polarization
Authors: Hu Jinyang , Dong Feng , He You , Xia Xianyou , Cheng Fangling , Chen Sui , Hou Xiaoshuang , Zhang Po , Liu Guohao , Li Ying , Gao Qian , Dong Minhai , Li Ting , Li Wei , Xiao Qungen , Li Xiaopeng , Yu Xingjiang , Xi Guifa , Guo Dongsheng , Wu Xudong , Wang Baofeng 
Published: September 2022

BackgroundGlioblastoma (GBM) is the most common malignant brain tumor with poor clinical outcomes. Immunotherapy has recently been an attractive and promising treatment of extracranial malignancies, however, most of clinical trials for GBM immunotherapy failed due to predominant accumulation of tumor-associated microglia/macrophages (TAMs).ResultsHigh level of LRIG2/soluble LRIG2 (sLRIG2) expression activates immune-related signaling pathways, which are associated with poor prognosis in GBM patients. LRIG2/sLRIGs promotes CD47 expression and facilitates TAM recruitment. Blockade of CD47–SIRPα interactions and inhibition of sLRIG2 secretion synergistically suppress GBM progression in an orthotropic murine GBM model.ConclusionsGBM cells with high level LRIG2 escape the phagocytosis by TAM via the CD47-SIRPα axis, highlighting a necessity for an early stage of clinical trial targeting LRIG2 and CD47-SIRPα as a novel treatment for patients with GBM.
N-cadherin protects oral cancer cells from NK cell killing in the circulation by inducing NK cell functional exhaustion via the KLRG1 receptor
Authors: Lou Chao , Wu Kailiu , Shi Jianbo , Dai Zhenlin , Xu Qin 
Published: September 2022

BackgroundCirculating tumor cells (CTCs) can survive in the circulation and return to primary tumors through a self-seeding process. However, the mechanisms underlying CTCs escape from natural killer (NK) cell-mediated immune surveillance remain unclear.MethodSelf-seeded tumor cells were isolated and characterized using a modified contralateral seeding model. A comparison of transcriptional profiles was performed between the parental cells and self-seeded cells. The molecular mechanism of self-seeded tumor cells escaping from NK cell was demonstrated through in vitro experiments and verified in a CTC-mimicking in vivo model. Then, the expression level of key protein mediating CTCs immune escape was detected in 24 paired primary and recurrent tumor samples of patients with oral cancer by the immunohistochemical method.ResultSelf-seeded cells displayed resistance to NK cell-mediated lysis and a higher tumor seeding ability than their parental cells. Elevated expression levels of the CDH2 gene and its protein product, N-cadherin were found in self-seeded cells. NK cells secreted cytokines, and fluid shear stress facilitated N-cadherin release by promoting A disintegrin and metalloprotease 10 (ADAM10) translation or converting the precursor ADAM10 to the mature form. Soluble N-cadherin triggered NK cell functional exhaustion by interacting with the killer cell lectin-like receptor subfamily G member 1 (KLRG1) receptor and therefore protected tumor cells from NK cell killing in the circulation. In vivo experimental results showed that overexpression of N-cadherin promoted tumor self-seeding and facilitated the survival of CTCs. Compared with primary tumors, N-cadherin expression was significantly increased in matched recurrent tumor tissues.ConclusionTogether, our findings illustrate an unknown mechanism by which CTCs evaded NK cell-mediated immune surveillance, and indicate that targeting N-cadherin is an effective strategy to prevent CTCs from homing to primary tumor.
COLAR: open-label clinical study of IL-6 blockade with tocilizumab for the treatment of immune checkpoint inhibitor-induced colitis and arthritis
Authors: Holmstroem Rikke Boedker , Nielsen Ole Haagen , Jacobsen Søren , Riis Lene Buhl , Theile Susann , Bjerrum Jacob Tveiten , Vilmann Peter , Johansen Julia Sidenius , Boisen Mogens Karsbøl , Eefsen Rikke Helene Løvendahl , Marie Svane Inge , Nielsen Dorte Lisbet , Chen Inna Markovna 
Published: September 2022

BackgroundImmune-related adverse events due to immune checkpoint inhibitors (ICIs) are not always effectively treated using glucocorticoids and it may negatively affect the antitumor efficacy of ICIs. Interventional studies of alternatives to glucocorticoids are lacking. We examined whether interleukin-6 blockade by tocilizumab reduced ICI-induced colitis and arthritis.Patients and methodsPatients with solid cancer experiencing Common Terminology Criteria for Adverse Events (CTCAE v5.0) grade >1 ICI-induced colitis/diarrhea (n=9), arthritis (n=9), or both (n=2) were recruited and treated with tocilizumab (8 mg/kg) every 4 weeks until worsening or unacceptable toxicity. Patients were not allowed to receive systemic glucocorticoids and other immunosuppressive drugs within the 14-day screening period. The primary endpoint was clinical improvement of colitis and arthritis, defined as ≥1 grade CTCAE reduction within 8 weeks. Secondary endpoints were improvements and glucocorticoid-free remission at week 24; safety; radiologic, endoscopic, and histological changes; and changes in plasma concentrations of C reactive protein, cytokines (IL-6, IL-8, and IL-17), and YKL-40.ResultsNineteen patients were available for efficacy analysis; one patient was excluded due to pancreatic insufficiency-induced diarrhea. Patients received treatment with pembrolizumab (n=10) or nivolumab (n=4) as monotherapy or ipilimumab and nivolumab (n=5) combined. Seven patients had been initially treated with glucocorticoids, and two of them also received infliximab. Ten patients continued ICI therapy during tocilizumab treatment. The primary endpoint was achieved in 15 of 19 (79%) patients. Additional one patient had ≥1 grade reduction at week 10, and another patient had stabilized symptoms. At week 24, ongoing improvement without glucocorticoids (n=12), including complete remission (n=10), was noted. Five patients had grades 3–4 treatment-related adverse events, which were manageable and reversible.ConclusionsTocilizumab showed promising clinical efficacy and a manageable safety profile in the treatment of ICI-induced colitis and arthritis. Our findings support the feasibility of randomized trials of immune-related adverse events.Trial registration numberNCT03601611.
Thiamine deficiency: a commonly unrecognised but easily treatable condition
Authors: Schostak Tritia , San Millan Iňigo , Jani Alkesh , Johnson Richard Joseph 
Published: September 2022

Abstract
Thiamine is present in many foods and is well recognised as an essential nutrient critical for energy metabolism. While thiamine deficiency is commonly recognised in alcoholism, it can present in many other settings where it is often not considered and goes unrecognised. One challenging aspect to diagnosis is that it may have varied metabolic, neurological and cardiac presentations. Here we present an overview of the disorder, focusing on the multiple causes and clinical presentations. Interestingly, thiamine deficiency is likely increasing in frequency, especially among wildlife, where it is linked with changing environments and climate change. Thiamine deficiency should be considered whenever neurological or cardiological disease of unknown aetiology presents, especially in any patient presenting with lactic acidosis.
Does gender influence outcome measures similarly in patients with spondyloarthritis? Results from the ASAS-perSpA study
Authors: Benavent Diego , Capelusnik Dafne , Ramiro Sofia , Molto Anna , López-Medina Clementina , Dougados Maxime , Navarro-Compán Victoria 
Published: September 2022

ObjectivesTo investigate the influence of gender on disease outcomes in patients with spondyloarthritis (SpA), including across SpA subtypes.MethodsData from 4185 patients of 23 countries with a diagnosis of axial SpA (axSpA), peripheral SpA (pSpA) or psoriatic arthritis (PsA) from the Assessment of SpondyloArthritis International Society (ASAS)-perSpA study were analysed. Associations between gender and disease activity (Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Score (BASDAI), C-reactive protein (CRP)), function (Bath Ankylosing Spondylitis Functional Index (BASFI)) and overall health (ASAS Health Index (ASAS HI), European Quality of Life Five Dimension (EQ-5D)) outcomes were investigated. Multilevel multivariable linear mixed models adjusted for relevant confounders (and stratified by disease subtype in case of a relevant interaction) were used.ResultsIn total, 65%, 10% and 25% of patients had axSpA, pSpA and PsA, respectively. axSpA was more frequent in males (68%), whereas pSpA and PsA were more frequent in females (53% and 52%, respectively). A significant interaction between gender and disease subtype was found for ASDAS, BASDAI and BASFI. While being female independently contributed to higher BASDAI across the three disease subtypes (with varying magnitude), female gender was only associated with higher ASDAS in pSpA (β (95% CI): 0.36 (0.15 to 0.58)) and PsA (0.25 (0.12 to 0.38)) but not in axSpA (0.016 (−0.07 to 0.11)). No associations were observed between gender and CRP levels. Female gender was associated with higher ASAS HI and EQ-5D, without differences across disease subtype.ConclusionFemale gender is associated with less favourable outcome measures across the SpA spectrum. However, while female gender influences BASDAI across the three subtypes, ASDAS is associated with gender only in pSpA and PsA but not in axSpA. Therefore, ASDAS is an appropriate instrument both for females and males with axSpA.
Gaussian discriminators between $$\varLambda $$CDM and wCDM cosmologies using expansion data
Authors: Mehrabi Ahmad , Said Jackson Levi 
Published: September 2022

AbstractThe Gaussian linear model provides a unique way to obtain the posterior probability distribution as well as the Bayesian evidence analytically. Considering the expansion rate data, the Gaussian linear model can be applied for $$\varLambda $$
Λ
CDM, wCDM and a non-flat $$\varLambda $$
Λ
CDM. In this paper, we simulate the expansion data with various precision and obtain the Bayesian evidence, then it has been used to discriminate the models. The data uncertainty is in range $$\sigma \in (0.5,10)\%$$

σ
∈
(
0.5
,
10
)
%

and two different sampling rates have been considered. Our results indicate that considering $$\sigma =0.5\%$$

σ
=
0.5
%

uncertainty, it is possible to discriminate 2$$\%$$
%
deviation in equation of state from $$w=-1$$

w
=
-
1

. On the other hand, we investigate how precision of the expansion rate data affects discriminating the $$\varLambda $$
Λ
CDM from a non-flat $$\varLambda $$
Λ
CDM model. Finally, we perform a parameters inference in both the MCMC and Gaussian linear model, using current available expansion rate data and compare the results.
Multi-omics Uncovering Different Faces of Clear Cell Ovarian Cancer
Authors: Lheureux Stephanie 
Published: September 2022

SummaryThe diagnosis of clear cell ovarian cancer relies on expert histopathology review. Further characterization from deep genomic and transcriptomic analyses can identify different subgroups. International collaboration is required to define the clinical impact and therapy opportunities in these specific subclassifications.See related article by Bolton et al., p. 4947
ICBatlas: A Comprehensive Resource for Depicting Immune Checkpoint Blockade Therapy Characteristics from Transcriptome Profiles
Authors: Yang Mei , Miao Ya-Ru , Xie Gui-Yan , Luo Mei , Hu Hui , Kwok Hang Fai , Feng Jian , Guo An-Yuan 
Published: September 2022

Abstract

Immune checkpoint blockade (ICB) therapy provides remarkable clinical benefits for multiple cancer types. Much work is currently being conducted to investigate the mechanisms of ICB therapy at the transcriptional level. Integrating the data produced by these studies will help us give more insight into the transcriptomic features of ICB therapy. We collected the transcriptome and clinical data of ICB-treated patient samples from the Gene Expression Omnibus, ArrayExpress, The Cancer Genome Atlas, and dbGaP databases. On the basis of the clinical information, all samples are initially classified into response/nonresponse or pretreatment/on-treatment groups. Differential expression, pathway enrichment, and immune cell infiltration analyses are performed between the samples from different groups. We also introduce the Response Score (RS) calculated by integrating the variability degree and the frequency of the dysregulated genes in the responders to evaluate the impact of gene expression on the response. Finally, all the abovementioned contents are integrated into the ICBatlas database. ICBatlas provides the transcriptome features of ICB therapy through the analysis of 1,515 ICB-treated samples from 25 studies across nine cancer types. The data in ICBatlas include clinical outcomes, treatment-related genes, biological pathways, and immune cell infiltration. Users can investigate the abovementioned transcriptome features in the response (R vs. NR) or treatment (Pre vs. On) modules at the data set, cancer type, or immune checkpoint level and compare the degree of gene impact on the response in the RS module. ICBatlas is the first database to show the transcriptome features on ICB therapy in human cancers and freely available at http://bioinfo.life.hust.edu.cn/ICBatlas/.
First Detection of the Pekeris Internal Global Atmospheric Resonance: Evidence from the 2022 Tonga Eruption and from Global Reanalysis Data
Authors: Watanabe Shingo , Hamilton Kevin , Sakazaki Takatoshi , Nakano Masuo 
Published: September 2022

Abstract
We used observations and model simulation to examine the atmospheric pulses that dominate the far field in the hours after the January 2022 Tonga eruption. We analyzed radiance observations taken from the Himawari-8 geostationary satellite and showed that both a Lamb wave front with the expected horizontal phase speed ∼315 m s−1 and a distinct front with phase speed ∼245 m s−1 can be detected. The slower phase speed is consistent with that expected for the global internal resonant mode that had been proposed by Pekeris in 1937 and in other idealized theoretical studies over the past century, but which had never been detected in the atmosphere. A simulation of the eruption aftermath was performed with a high-resolution atmospheric general circulation model. A hot anomaly over the volcano location was introduced instantaneously to the model fields and the model was integrated for another 12 h. This produced a simulated wave pulse that, in the far field, agreed reasonably well with barograph observations of the Lamb wave. The model results also showed the presence of the slower pulse and that this disturbance had a vertical structure with a 180° phase shift in the stratosphere, in agreement with the theoretical prediction for the internal resonant mode. An implication is that the continuously ringing Lamb wave global normal modes that have been seen in analyses of long observational records ought to have lower-frequency internal Pekeris mode counterparts, a prediction that we confirm though analysis of 67 years of hourly global reanalysis data.

Significance Statement
Our demonstration that both a surface-trapped Lamb wave and a slower horizontal phase speed internal Pekeris wave can be realized as normal modes of the global atmosphere resolves a very long-standing and fundamental issue in dynamical meteorology. Our result also has broader implications. The 2022 Tonga eruption produced a surprisingly large ocean tsunami even in a remote ocean basin, and it is possible that the slower atmospheric Pekeris mode can play a role in exciting the remarkable ocean response. Also the spectral peaks seen in atmospheric variability corresponding to the Pekeris normal mode provide features for comparison with global model simulations of the atmosphere, along with the Lamb modes detected in earlier studies.
Detection of Sea Surface Temperature Fronts from SAR Images
Authors: Zhao Li , Xie Tao , Perrie William , Ma Ming , Yang Jingsong , Bai Chengzu , Danielson Rick 
Published: September 2022

Abstract
Sea surface temperature (SST) fronts are important for fisheries and marine ecology, as well as upper-ocean dynamics, weather forecasting, and climate monitoring. In this paper, we propose a new approach to detect SST fronts from RADARSAT-2 ScanSAR images, based on the correlation of SAR-derived wind speeds using the gray level cooccurrence matrix (GLCM) approach. Due to the large differences between the correlation of wind speeds for SST fronts compared to other areas, SST fronts can be detected by the threshold method. To eliminate small-scale features (or noise), the 30 km scale is used as the length threshold for the detection of the SST fronts. The proposed method is effective when wind speeds are between 3 and 13 m s−1. The overall accuracy of our method is about 93.6%, which is sufficient for operational applications.
Evaluation of Turbulence and Dispersion in Multiscale Atmospheric Simulations over Complex Urban Terrain during the Joint Urban 2003 Field Campaign
Authors: Wiersema David J. , Lundquist Katherine A. , Mirocha Jeffrey D. , Katopodes Chow Fotini 
Published: September 2022

Abstract
This paper evaluates the representation of turbulence and its effect on transport and dispersion within multiscale and microscale-only simulations in an urban environment. These simulations, run using the Weather Research and Forecasting Model with the addition of an immersed boundary method, predict transport and mixing during a controlled tracer release from the Joint Urban 2003 field campaign in Oklahoma City, Oklahoma. This work extends the results of a recent study through analysis of turbulence kinetic energy and turbulence spectra and their role in accurately simulating wind speed, direction, and tracer concentration. The significance and role of surface heat fluxes and use of the cell perturbation method in the numerical simulation setup are also examined. Our previous study detailed the model development necessary for our multiscale simulations, examined model skill at predicting wind speeds and tracer concentrations, and demonstrated that dynamic downscaling from mesoscale to microscale through a sequence of nested simulations can improve predictions of transport and dispersion relative to a microscale-only simulation forced by idealized meteorology. Here, predictions are compared with observations to assess qualitative agreement and statistical model skill at predicting wind speed, wind direction, tracer concentration, and turbulent kinetic energy at locations throughout the city. We also investigate the scale distribution of turbulence and the associated impact on model skill, particularly for predictions of transport and dispersion. Our results show that downscaled large-scale turbulence, which is unique to the multiscale simulations, significantly improves predictions of tracer concentrations in this complex urban environment.

Significance Statement
Simulations of atmospheric transport and mixing in urban environments have many applications, including pollution modeling for urban planning or informing emergency response following a hazardous release. These applications include phenomena with spatial scales spanning from millimeters to kilometers. Most simulations resolve flow only within the urban area of interest, omitting larger scales of turbulence and regional influences. This study examines a method that resolves both the small and large-scale flow features. We evaluate simulation accuracy by comparing predictions with observations from an experiment involving the release of a tracer gas in Oklahoma City, Oklahoma, with emphasis on correctly modeling turbulent fluctuations. Our results demonstrate the importance of resolving large-scale flow features when predicting transport and dispersion in urban environments.
Is Climate Change Migration an Adjustment to Extreme Weather Events? A Study on the Coastal Areas of Bangladesh
Authors: Islam Mozharul 
Published: September 2022

Abstract
This paper explores the internal migration of fishers from coastal communities of Bangladesh in response to extreme weather events. It also assesses the vulnerabilities to extreme weather events of these coastal areas, in general, and of targeted fishing communities, in particular. This qualitative study employs a combination of methods, semistructured interviews and observations, in two villages located in the eastern part of Kalapara Upazila, Patuakhali district of Bangladesh. The results indicate that the participants of the study are susceptible to the vulnerability of extreme weather events due to their households’ socioeconomic and geographical location. This study shows that most people from the fishing communities do not migrate to other places to escape from the vulnerabilities as they have high dependency on fish-related activities. Also, there are various socioeconomic and cultural factors that hinder their migration, including the Mohajon–Dadon system, migration costs, lack of skills and resources, and fear of income insecurity. Instead of migrating, they develop their own traditional adaptation mechanisms to ensure their survival. These people remain underrepresented and are not adequately recorded in national or regional migration data.
Measuring Deltoid Insufficiency After Supination-External Rotation Ankle Fracture With Lateral Talar Subluxation on Gravity Stress View
Authors: Haupt Edward T. , Sebro Ronnie , Iturregui Jose M. , Stanborough Rupert , Siddiqui Ali , Shi Glenn G. 
Published: September 2022

Background: Stress-view radiographs are frequently obtained to evaluate supination-external rotation (SER) variant ankle fractures. Measurement of the ankle medial clear space (MCS) is a surrogate of medial structure integrity as part of overall ankle stability. Measurement of the lateral talus displacement with respect to the incisura may be a sensitive and specific method to assess joint subluxation. Methods: Retrospective review of acute SER-variant isolated lateral malleolar fractures with gravity stress views (GSVs) were performed for 103 patients. GSV analysis was performed with standardized measurements of the MCS, superior clear space (SCS), and 2 new novel measurements of lateral talus subluxation (LTS). Decision for surgery was obtained by surgeons who reviewed masked injury radiographs for predictive performance analysis of the LTS vs MCS. Results: MCS, SCS, and LTS measurements were performed on 103 patients. Mean MCS, SCS, and LTS within the operative group was increased. MCS ≥5 mm and LTS >4 mm had equal sensitivity (95%), with higher specificity for LTS (75% vs 60%). Receiver operating characteristic analysis demonstrates an area under the curve of 0.786 for MCS ≥5 mm vs 0.918 for LTS >4 mm. Conclusion: We found LTS to be superior to MCS for medial ankle structure stability on gravity stress views of SER-variant ankle fractures. We propose this as a useful tool for clinicians to consider when evaluating SER-variant ankle fractures. Level of Evidence: Level II, prospective comparative study of radiographs.