bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whittaker vectors for $$\mathcal {W}$$-algebras from topological recursion
Authors: Borot Gaëtan , Bouchard Vincent , Chidambaram Nitin K. , Creutzig Thomas 
Published: March 2024

AbstractWe identify Whittaker vectors for $$\mathcal {W}^{\textsf{k}}(\mathfrak {g})$$

W

k

(
g
)

-modules with partition functions of higher Airy structures. This implies that Gaiotto vectors, describing the fundamental class in the equivariant cohomology of a suitable compactification of the moduli space of G-bundles over $$\mathbb {P}^2$$

P

2

for G a complex simple Lie group, can be computed by a non-commutative version of the Chekhov–Eynard–Orantin topological recursion. We formulate the connection to higher Airy structures for Gaiotto vectors of type A, B, C, and D, and explicitly construct the topological recursion for type A (at arbitrary level) and type B (at self-dual level). On the physics side, it means that the Nekrasov partition function for pure $$\mathcal {N} = 2$$

N
=
2

four-dimensional supersymmetric gauge theories can be accessed by topological recursion methods.
That’s BAD: blind anomaly detection by implicit local feature clustering
Authors: Zhang Jie , Suganuma Masanori , Okatani Takayuki 
Published: March 2024

AbstractRecent studies on visual anomaly detection (AD) of industrial objects/textures have achieved quite good performance. They consider an unsupervised setting, specifically the one-class setting, in which we assume the availability of a set of normal (i.e., anomaly-free) images for training. In this paper, we consider a more challenging scenario of unsupervised AD, in which we detect anomalies in a given set of images that might contain both normal and anomalous samples. The setting does not assume the availability of known normal data and thus is completely free from human annotation, which differs from the standard AD considered in recent studies. For clarity, we call the setting blind anomaly detection (BAD). We show that BAD can be converted into a local outlier detection problem and propose a novel method named PatchCluster that can accurately detect image- and pixel-level anomalies. Experimental results show that PatchCluster shows a promising performance without the knowledge of normal data, even comparable to the SOTA methods applied in the one-class setting needing it.
Level-k thinking in the extensive form
Authors: Schipper Burkhard C. , Zhou Hang 
Published: March 2024

AbstractLevel-kthinking has been widely applied as a solution concept for games in normal form in behavioral and experimental game theory. We consider level-k thinking in games in extensive form. Player’s may learn about levels of opponents’ thinking during the play of the game because some information sets may be inconsistent with certain levels. In particular, for any information set reached, a level-kplayer attaches the maximum level-$$\ell $$ℓthinking for$$\ell < k$$ℓ<kto her opponents consistent with the information set. We compare our notion of strong level-kthinking with other solution concepts such as level-kthinking in the associated normal form, strong rationalizability,$$\Delta $$Δ-rationalizability, iterated admissibility, backward rationalizability, backward level-kthinking, and backward induction. We use strong level-kthinking to reanalyze data from some prior experiments in the literature.
Clinical immunotherapy in pancreatic cancer
Authors: Ye Xiaorong , Yu Yue , Zheng Xiaohu , Ma Hongdi 
Published: March 2024

AbstractPancreatic cancer remains a challenging disease with limited treatment options, resulting in high mortality rates. The predominant approach to managing pancreatic cancer patients continues to be systemic cytotoxic chemotherapy. Despite substantial advancements in immunotherapy strategies for various cancers, their clinical utility in pancreatic cancer has proven less effective and durable. Whether administered as monotherapy, employing immune checkpoint inhibitors, tumor vaccines, chimeric antigen receptors T cells, or in combination with conventional chemoradiotherapy, the clinical outcomes remain underwhelming. Extensive preclinical experiments and clinical trials in the realm of pancreatic cancer have provided valuable insights into the complexities of immunotherapy. Chief among the hurdles are the immunosuppressive tumor microenvironment, limited immunogenicity, and the inherent heterogeneity of pancreatic cancer. In this comprehensive review, we provide an overview and critical analysis of current clinical immunotherapy strategies for pancreatic cancer, emphasizing their endeavors to overcome immunotherapy resistance. Particular focus is placed on strategies aimed at reshaping the immunosuppressive microenvironment and enhancing T cell-mediated tumor cell killing. Ultimately, through deeper elucidation of the underlying pathogenic mechanisms of pancreatic cancer and the refinement of therapeutic approaches, we anticipate breakthroughs that will pave the way for more effective treatments in this challenging disease.
Size selection of intrahepatic lesions for cryoablation contributes to abscopal effect and long-term survival in patients with liver metastatic melanoma receiving PD-1 blockade therapy
Authors: Shen Lujun , Tan Hongtong , Nie Juan , Jiang Yiquan , Nuerhashi Gulijiayina , Qi Han , Cao Fei , Wen Chunyong , Chen Shuanggang , Zhang Tianqi , Zheng Wei , Liu Peng , Liu Ying , Huang Tao , Li Dandan , Zhang Xiaoshi , Fan Weijun 
Published: March 2024

Abstract
Objectives
In this study, we aimed to examine parameters of cryoablation, tumor characteristics, and their correlations with distant tumor response and survival of liver metastatic melanoma patients receiving cryoablation and PD-1 blockade (cryo-PD-1) combination treatment.

Materials and methods
A retrospective study was conducted among 45 melanoma patients who received combined PD-1 blockade therapy and cryoablation for liver metastasis from 2018 to 2022. Cox regression was utilized to determine the associations between factors and overall survival (OS). Changes in cytokines and immune cell compositions in peripheral blood samples following the combined treatment were investigated, along with their correlations with treatment response.

Results
The mean cycle of cryo-PD-1 combination treatment was 2.2 (range, 1–6), and the 3-month overall response rate (RECIST 1.1 criteria) was 26.7%. Of the 21 patients who failed previous PD-1 blockade therapy after diagnosis of liver metastasis, 4 (19.0%) achieved response within 3 months since combination treatment. The diameter of ablated lesion  ≤ 30 mm, metastatic organs  ≤ 2, and pre-treatment LDH level  ≤ 300 U/L were independent prognostic factors for favorable OS. Further analysis showed patients with intrahepatic tumor size of 15–45 mm, and ablated lesion size of  ≤ 30 mm had significantly higher 3-month response rate (42.9% vs 12.5%; P = 0.022) and survival time (30.5 vs 14.2 months; P = 0.045) than their counterparts. The average increase in NLR among patients with ablated tumor size of  ≤ 3 cm and  > 3 cm were 3.59 ± 5.01 and 7.21 ± 12.57, respectively. The average increase in serum IL-6 levels among patients with ablated tumor size of  ≤ 3 cm and  > 3 cm were 8.62 ± 7.95 pg/ml and 15.40 ± 11.43 pg/ml, respectively.

Conclusion
Size selection of intrahepatic lesions for cryoablation is important in order to achieve abscopal effect and long-term survival among patients with liver metastatic melanoma receiving PD-1 blockade therapy.
Outcomes in biomarker-selected subgroups from the KESTREL study of durvalumab and tremelimumab in recurrent or metastatic head and neck squamous cell carcinoma
Authors: Seiwert Tanguy Y. , Wildsmith Sophie , Fayette Jérôme , Harrington Kevin , Gillison Maura , Ahn Myung-Ju , Takahashi Shunji , Weiss Jared , Machiels Jean-Pascal , Baxi Shrujal , Baker Valerie , Evans Brent , Morsli Nassim , Jill Walker  , Real Katia , L’Hernault Anne , Psyrri Amanda 
Published: March 2024

Abstract
Background
Selective biomarkers may improve outcomes in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) treated with immune checkpoint inhibitor therapy. We investigated three independent biomarkers for association with efficacy in the randomized, phase III KESTREL study (NCT02551159) of first-line durvalumab monotherapy or durvalumab plus tremelimumab versus the EXTREME regimen: programmed cell death ligand-1 (PD-L1) immunohistochemistry, blood tumor mutational burden (bTMB) via circulating tumor DNA, and neutrophil-to-lymphocyte ratio (NLR).

Methods
Tumor or blood samples from patients enrolled in the KESTREL study were analyzed for PD-L1, bTMB, and NLR. Associations with overall survival (OS) or objective response rates (ORRs) were evaluated based on prespecified cut-offs for PD-L1 (tumor cell [TC] ≥ 50%/immune cell ≥ 25% or TC ≥ 25%), bTMB (≥ 16 mutations [mut] per megabase [Mb]), and NLR (≤ 7). Ad hoc analyses of exploratory cut-offs were performed.

Results
Prespecified or exploratory cut-offs for PD-L1 did not enrich for ORR or OS for durvalumab monotherapy or durvalumab plus tremelimumab versus EXTREME. In the bTMB ≥ 16 mut/Mb subgroup, OS hazard ratios (95% confidence interval) for durvalumab monotherapy and durvalumab plus tremelimumab versus EXTREME were 0.90 (0.48–1.72) and 0.69 (0.39–1.25), respectively. Complete response rates were 8.6% with durvalumab plus tremelimumab and 4.3% with EXTREME (≥ 16 mut/Mb subgroup). No improvement in OS was observed for durvalumab monotherapy or durvalumab plus tremelimumab versus EXTREME at prespecified or exploratory NLR cut-offs.

Conclusions
bTMB demonstrated potential utility for selecting patients with R/M HNSCC who benefited from durvalumab with or without tremelimumab versus EXTREME.
Trial registration ClinicalTrials.gov identifier NCT02551159.
Integrating molecular subtype and CD8+ T cells infiltration to predict treatment response and survival in muscle-invasive bladder cancer
Authors: Li Bingyu , Jin Kaifeng , Liu Zhaopei , Su Xiaohe , Xu Ziyue , Liu Ge , Xu Jingtong , Liu Hailong , Chang Yuan , Wang Yiwei , Zhu Yu , Wang Zewei , Xu Le , Zhang Weijuan 
Published: March 2024

Abstract
Background
Luminal and Basal are the primary intrinsic subtypes of muscle-invasive bladder cancer (MIBC). The presence of CD8+ T cells infiltration holds significant immunological relevance, potentially influencing the efficacy of antitumor responses. This study aims to synergize the influence of molecular subtypes and CD8+ T cells infiltration in MIBC.

Methods
This study included 889 patients with MIBC from Zhongshan Hospital, The Cancer Genome Atlas, IMvigor210 and NCT03179943 cohorts. We classified the patients into four distinct groups, based on the interplay of molecular subtypes and CD8+ T cells and probed into the clinical implications of these subgroups in MIBC.

Results
Among patients with Luminal-CD8+Thigh tumors, the confluence of elevated tumor mutational burden and PD-L1 expression correlated with a heightened potential for positive responses to immunotherapy. In contrast, patients featured by Luminal-CD8+Tlow displayed a proclivity for deriving clinical advantages from innovative targeted interventions. The Basal-CD8+Tlow subgroup exhibited the least favorable three-year overall survival outcome, whereas their Basal-CD8+Thigh counterparts exhibited a heightened responsiveness to chemotherapy.

Conclusions
We emphasized the significant role of immune-molecular subtypes in shaping therapeutic approaches for MIBC. This insight establishes a foundation to refine the process of selecting subtype-specific treatments, thereby advancing personalized interventions for patients.
Mechanism exploration of Zoledronic acid combined with PD-1 in the treatment of hepatocellular carcinoma
Authors: Fan Xinru , Yan Zijun , Lin Yunkai , Wang Qing , Jiang Li , Yao Xiaomeng , Dong Liwei , Chen Lei , Zhao Tuan , Zhao Jieqiong , Hu Heping , Wang Hui 
Published: March 2024

AbstractHow to increase the response of immune checkpoint inhibitors (ICIs) is a challenge. In clinical, we found that Zoledronic acid (ZA) may increase the anti-tumor effect of immunotherapy for hepatocellular carcinoma (HCC). To explore the underlying mechanism, we established a mouse model of HCC by subcutaneously injecting Hepa1-6 cell line. The result showed that the tumor volume in the ZA plus anti-PD-1 monocloning antibody (anti-PD-1 mAb) treatment groups was significantly smaller than that of control group, and the onset time of tumor inhibition was even shorter than that of the anti-PD-1 mAb group. Using flow cytometry (FC) to detect the proportion of major immune cell subsets in tumor tissues of each group of mice, we found that the synergistic anti-tumor effect of ZA and anti-PD-1 mAb may be related to ZA-induced polarization of macrophages toward the M1 phenotype. Next, we performed bulk RNA sequencing on tumor samples from different groups to obtain differentially expressed genes (DEGs), which were then input DEGs into pathway enrichment analysis. Data indicated that ZA participated in the M1-type polarization via ferroptosis-related pathways. Our results revealed how ZA involves in the anti-tumor effect of PD-1 monoclonal antibody and provided a potential therapeutic candidate for patients with HCC.
Construction of an immune predictive model and identification of TRIP6 as a prognostic marker and therapeutic target of CRC by integration of single-cell and bulk RNA-seq data
Authors: Liu Wenjun , Luo Xitu , Zhang Zilang , Chen Yepeng , Dai Yongliang , Deng Jianzhong , Yang Chengyu , Liu Hao 
Published: March 2024

Abstract
Background
Investigations elucidating the complex immunological mechanisms involved in colorectal cancer (CRC) and accurately predicting patient outcomes via bulk RNA-Seq analysis have been notably limited. This study aimed to identify the immune status of CRC patients, construct a prognostic model, and identify prognostic signatures via bulk RNA sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq).

Methods
The scRNA-seq data of CRC were downloaded from Gene Expression Omnibus (GEO). The UCSC Xena database was used to obtain bulk RNA-seq data. Differentially expressed gene (DEG), functional enrichment, and random forest analyses were conducted in order to identify core genes associated with colorectal cancer (CRC) that were relevant to prognosis. A molecular immune prediction model was developed using logistic regression after screening features using the least absolute shrinkage and selection operator (LASSO). The differences in immune cell infiltration, mutation, chemotherapeutic drug sensitivity, cellular senescence, and communication between patients who were at high and low risk of CRC according to the predictive model were investigated. The prognostic genes that were closely associated with CRC were identified by random survival forest (RSF) analysis. The expression levels and clinical significance of the hub genes were analyzed in vitro. The LoVo cell line was employed to ascertain the biological role of thyroid hormone receptor-interacting protein 6 (TRIP6).

Results
A total of seven main cell subtypes were identified by scRNA-seq analysis. A molecular immune predictive model was constructed based on the risk scores. The risk score was significantly associated with OS, stage, mutation burden, immune cell infiltration, response to immunotherapy, key pathways, and cell–cell communication. The functions of the six hub genes were determined and further utilized to establish a regulatory network. Our findings unequivocally confirmed that TRIP6 upregulation was verified in the CRC samples. After knocking down TRIP6, cell proliferation, migration, and invasion of LoVo cells were inhibited, and apoptosis was promoted.

Conclusions
The molecular predictive model reliably distinguished the immune status of CRC patients. We further revealed that TRIP6 may act as an oncogene in CRC, making it a promising candidate for targeted therapy and as a prognostic marker for CRC.
Paracetamol transport by ZnO nanoparticle-doped polymer-containing membrane
Authors: Selimoglu Faysal , Akin Ilker , Ayhan Muhammed Emre 
Published: March 2024

AbstractIn this study, the transport performance of acetaminophen (paracetamol), which is most commonly prescribed and used for humans and animals and whose wastes are known to have toxic effects on the environment and some living organisms, was investigated using zinc oxide (ZnO)-reinforced polymer membranes. In this study, nanoparticle-containing polymer membranes were prepared from cellulose triacetate in dichloromethane and ZnO nanoparticles were synthesized to impart adsorption properties to the membrane in a single step, enabling adsorption and filtration to improve the removal of low molecular weight micropollutants that are poorly retained by conventional polymer membranes and by enabling re-release. Our membrane was prepared by phase inversion method by doping with cellulose triacetate (CTA) solution. Parameters such as carrier concentration, mixing rate, transport time, acceptor and feed phase concentrations were studied to determine the optimal conditions for the transport experiments of paracetamol (PARA). The presence of acid in the acceptor phase converted the hydrophilic part of paracetamol, which allowed the transport of PARA. The calculated flux values for different PARA concentrations ranged from (0.64) × 10−8 to (1.8) × 10−8 mol/(cm2s). Under optimal conditions, a transport efficiency of 84% was obtained for PARA with a CTA/ZnO polymer membrane. The obtained membranes can be used in wastewater treatment, recovery of pharmacological products from pharmaceutical industry waste, re-evaluation of hospital waste, etc.
Bioactive glass doped with zinc-based metal–organic frameworks (Zn/MOF) nanoparticles for antibiotic delivery applications
Authors: Ahmed Manar M. , Omar Areg E. , Zayed Heba S. , Moaness Mona 
Published: March 2024

AbstractZn-MOF/bioactive glass nanoparticles were successfully prepared using quick–alkali-modified sol–gel and tested for gentamicin drug delivery. Samples of 0 and 0.8 mol% Zn MOF contents (BG and BG/Zn MOF, respectively) were characterized using XRD, FTIR, TEM, and SEM/EDX. In addition, zeta characteristics and surface area parameters were also evaluated. Moreover, the cell viability of the prepared samples was tested against the osteosarcoma MG-63 cell line to evaluate the ability of prepared samples for bone regeneration. In addition, the antimicrobial activity of glass samples with and without antibiotics was determined against different microorganisms. Finally, the samples were loaded with gentamicin drug, and drug release profile and kinetics were studied too. XRD and FTIR results confirmed the physicochemical properties of the prepared samples. TEM results showed that particles were in the nano-sized range in both samples; however, the presence of Zn MOF increased the dispersity of particles. Both samples were bioactive, as indicated by hydroxyapatite formation on their surfaces. Cytotoxicity estimation of prepared materials exhibited their safe and nontoxic nature. BG/Zn MOF sample demonstrated prolonged drug release and excellent antimicrobial activity in comparison to BG alone. Therefore, the present study provides promising preliminary results regarding the usage of BG/Zn MOF nanoparticles loaded with gentamicin as an effective approach for bone regeneration.
Graphical Abstract
Risk of death, thrombotic and hemorrhagic events in anticoagulated patients with atrial fibrillation and systemic autoimmune diseases: an analysis from a global federated dataset
Authors: Bucci Tommaso , Cardamone Chiara , Triggiani Massimo , Ames Paul R. J. , Lip Gregory Y. H. 
Published: March 2024

Abstract
Background
Growing evidence showing that systemic autoimmune diseases (SADs) are associated with a high risk of atrial fibrillation (AF). However, the impact of SAD on the clinical course of AF patients is largely unknown.

Methods
Retrospective cohort study within a federated healthcare network (TriNetX). Using ICD codes, AF patients on anticoagulant therapy were categorized according to the presence of SAD (M32: Systemic Lupus Erythematosus (SLE); M33: Dermato-polymyositis (DMP); M34: Systemic Sclerosis (SSc); M35: Sjogren syndrome). The primary outcomes were the 5-year risks of (1) all-cause death, (2) thrombotic events (ischemic stroke, acute myocardial infarction, deep vein thrombosis, and pulmonary embolism), and (3) bleeding (intracranial (ICH) and gastrointestinal (GI)). Secondary outcomes were each component of the primary outcomes. Cox regression analysis after propensity score matching (PSM) was used to estimate hazard ratio (HR) and 95% confidence interval (95%CI).

Results
We identified 16,098 AF patients with SAD (68.2 ± 13.4 years; 71.0% female) and 828,772 AF controls (70.7 ± 12.9 years, 41.1% females). After PSM, AF patients with SAD were associated with a higher risk of all-cause death (HR 1.13, 95%CI 1.09–1.71), thrombotic events (HR 1.37, 95%CI 1.32–1.43), and hemorrhagic events (HR 1.41, 95%CI 1.33–1.50) compared to AF controls without SAD. The highest risk of all-cause death and GI bleeding was associated with SSc, while the highest risk of thrombotic events and ICH was associated with SLE.

Conclusion
AF patients with SAD are associated with a high risk of all-cause death, thrombotic, and hemorrhagic events. These patients merit careful follow-up and integrated care management to improve their prognosis.

Graphical Abstract
Diet quality in relation to kidney function and its potential interaction with genetic risk of kidney disease among Dutch post-myocardial infarction patients
Authors: van Westing Anniek C. , Heerkens Luc , Cruijsen Esther , Voortman Trudy , Geleijnse Johanna M. 
Published: March 2024

Abstract
Purpose
We examined the relation between diet quality, its components and kidney function decline in post-myocardial infarction (MI) patients, and we explored differences by genetic risk of chronic kidney disease (CKD).

Methods
We analysed 2169 patients from the Alpha Omega Cohort (aged 60–80 years, 81% male). Dietary intake was assessed at baseline (2002–2006) using a validated food-frequency questionnaire and diet quality was defined using the Dutch Healthy Diet Cardiovascular Disease (DHD-CVD) index. We calculated 40-months change in estimated glomerular filtration rate (eGFR, mL/min per 1.73m2). We constructed a weighted genetic risk score (GRS) for CKD using 88 single nucleotide polymorphisms previously linked to CKD. Betas with 95%-confidence intervals (CIs) were obtained using multivariable linear regression models for the association between DHD-CVD index and its components and eGFR change, by GRS.

Results
The average DHD-CVD index was 79 (SD 15) points and annual eGFR decline was 1.71 (SD 3.86) mL/min per 1.73 m2. The DHD-CVD index was not associated with annual eGFR change (per 1-SD increment in adherence score: -0.09 [95% CI -0.26,0.08]). Results for adherence to guidelines for red meat showed less annual eGFR decline (per 1-SD: 0.21 [0.04,0.38]), whereas more annual eGFR decline was found for legumes and dairy (per 1-SD: -0.20legumes [-0.37,-0.04] and − 0.18dairy [-0.34,-0.01]). Generally similar results were obtained in strata of GRS.

Conclusion
The DHD-CVD index for overall adherence to Dutch dietary guidelines for CVD patients was not associated with kidney function decline after MI, irrespective of genetic CKD risk. The preferred dietary pattern for CKD prevention in CVD patients warrants further research.