bluuebunny/crossref_metadata_2025 huggingface dataset:
Adiabatic and post-adiabatic hyperspherical treatment of the huge ungerade proton-hydrogen scattering length
Authors: Singh Shayamal , Greene Chris H.
Published: February 2024

While the hydrogen molecular ion is the simplest molecule in nature and very well studied in all of its properties, it remains an interesting system to use for explorations of fundamental questions. One such question treated in this study relates to finding an optimal adiabatic representation of the physics, i.e., the best adiabatic description that minimizes the role of nonadiabatic effects. As a test case explored here in detail, we consider the ungerade symmetry of H[Formula: see text], which is known to have a huge scattering length of order 750 Bohr radii, and an incredibly weakly bound excited state. We show that a hyperspherical adiabatic description does an excellent job of capturing the main physics. Our calculation yields a competitive scattering length and shows that nonadiabatic corrections are small and can even be adequately captured using the post-adiabatic theory of Klar and Fano.
Impact of the f-Reggeon exchanges on the observables of the single diffractive dissociation of nucleon at ultrahigh energies
Authors: Godizov A. A.
Published: February 2024

Single diffractive dissociation (SDD) of nucleon in high-energy proton-proton and proton-antiproton collisions is considered in terms of a simple two-Reggeon model with nonlinear Regge trajectories. It is demonstrated that the f-Reggeon impact on the corresponding cross-sections is not negligible up to the LHC energies. As well, it is shown that the account of the f-Reggeon exchanges allows to describe the elastic diffractive scattering (EDS) and SDD of nucleons at ultrahigh energies in the framework of a unified phenomenological scheme. The predictive value of the proposed model is verified.
CodeKGC: Code Language Model for Generative Knowledge Graph Construction
Authors: Bi Zhen , Chen Jing , Jiang Yinuo , Xiong Feiyu , Guo Wei , Chen Huajun , Zhang Ningyu
Published: February 2024

Current generative knowledge graph construction approaches usually fail to capture structural knowledge by simply flattening natural language into serialized texts or a specification language. However, large generative language model trained on structured data such as code has demonstrated impressive capability in understanding natural language for structural prediction and reasoning tasks. Intuitively, we address the task of generative knowledge graph construction with code language model: given a code-format natural language input, the target is to generate triples which can be represented as code completion tasks. Specifically, we develop schema-aware prompts that effectively utilize the semantic structure within the knowledge graph. As code inherently possesses structure, such as class and function definitions, it serves as a useful model for prior semantic structural knowledge. Furthermore, we employ a rationale-enhanced generation method to boost the performance. Rationales provide intermediate steps, thereby improving knowledge extraction abilities. Experimental results indicate that the proposed approach can obtain better performance on benchmark datasets compared with baselines.1
Decision Making for Self-Adaptation Based on Partially Observable Satisfaction of Non-Functional Requirements
Authors: Garcia Luis , Samin Huma , Bencomo Nelly
Published: February 2024

Approaches that support the decision-making of self-adaptive and autonomous systems (SAS) often consider an idealized situation where (i) the system’s state is treated as fully observable by the monitoring infrastructure, and (ii) adaptation actions are assumed to have known, deterministic effects over the system. However, in practice, the system’s state may not be fully observable, and the adaptation actions may produce unexpected effects due to uncertain factors. This article presents a novel probabilistic approach to quantify the uncertainty associated with the effects of adaptation actions on the state of a SAS. Supported by Bayesian inference and POMDPs (Partially-Observable Markov Decision Processes), these effects are translated into the satisfaction levels of the non-functional requirements (NFRs) to, therefore, drive the decision-making. The approach has been applied to two substantial case studies from the networking and Internet of Things (IoT) domains, using two different POMDP solvers. The results show that the approach delivers statistically significant improvements in supporting decision-making for SAS.
Revolutionizing HPV Detection: Unveiling a Novel Electrochemical Immunosensor for Ultra-Sensitive HPV16 E7 Oncoprotein Detection Based on Gold-Graphitic Carbon Nitride Nanocomposite
Authors: Kotal Hiranmoy , Kalyani Thangapandi , Sangili Arumugam , Mandal Ranajit Kumar , Ghorai Suvankar , Jana Saikat Kumar
Published: February 2024

Cervical cancer (CC), a significant contributor to the mortality of females globally, manifests an annual incidence of 500,000 cases and is predominantly linked to the human papillomavirus (HPV) infection. The pressing demand for affordable and user-friendly assays for CC detection is highlighted by the limited availability and dependability of diagnostic screening tools, especially in developing countries. In response to the critical need for enhanced cervical cancer diagnostics, we present an innovative electrochemical immunosensor designed for the selective detection of the HPV 16-E7 oncoprotein. The immunosensing platform is constructed from a gold-graphitic carbon nitride (Au-g-C3N4) nanocomposite, with antibodies immobilized through a physical adsorption process onto the sensing platform. Employing Square Wave Voltammetry (SWV), we systematically evaluated the antigen-antibody interaction, achieving ultrasensitive detection of E7 with ferric/ferrocyanide. The linear detection range of the proposed sensor for E7 antigen is 0.01 fg ml−1 to 1 ng ml−1, assuming ideal conditions and an impressive Limit of Detection (LOD) of 0.0065 fg ml−1. The accuracy of the proposed immunosensor was effectively evaluated in contrast to Enzyme linked immunosorbent assay (ELISA). Finally, the proposed immunosensor exhibited favourable selectivity, sensitivity, and reproducibility upon introduction to clinical samples, thereby validating its potential suitability for point-of-care testing aimed at the timely detection of CC.
Comparative Thermal Insulation Nature of Ca2FeMnO6−δ
and Sr2FeMnO6−δ
Authors: Schultz Ebony , Guinn Mandy , Azure Alexa D. , Hona Ram Krishna
Published: February 2024

In this study, we investigate the utility of Ca2FeMnO6-δ
and Sr2FeMnO6-δ
as materials with low thermal conductivity, finding potential applications in thermoelectrics, electronics, solar devices, and gas turbines for land and aerospace use. These compounds, characterized as oxygen-deficient perovskites, feature distinct vacancy arrangements. Ca2FeMnO6-δ
adopts a brownmillerite-type orthorhombic structure with ordered vacancy arrangement, while Sr2FeMnO6-δ
adopts a perovskite cubic structure with disordered vacancy distribution. Notably, both compounds exhibit remarkably low thermal conductivity, measuring below 0.50 Wm−1K−1. This places them among the materials with the lowest thermal conductivity reported for perovskites. The observed low thermal conductivity is attributed to oxygen vacancies and phonon scattering. Interestingly as SEM images show the smaller grain size, our findings suggest that creating vacancies and lowering the grain size or increasing the grain boundaries play a crucial role in achieving such low thermal conductivity values. This characteristic enhances the potential of these materials for applications where efficient heat dissipation, safety, and equipment longevity are paramount.
Effect of electrical muscle stimulation on cerebrovascular function and cognitive performance
Authors: Descollonges Maël , Marmier Paul , Marillier Mathieu , Jafari Ehsan , Brugniaux Julien V. , Deley Gaëlle
Published: February 2024

This study is the first to demonstrate that one session of EMS applied to the quadriceps increases cerebral blood flow velocity and cerebral oxygenation, which are pivotal factors for brain health. Thus, EMS has the potential to be used as an interesting option in rehabilitation to increase cerebral perfusion and defend if not improve cognitive function sustainably for people with severe physical limitations who would not be able to perform physical exercise voluntarily.
Calcium signaling in endothelial and vascular smooth muscle cells: sex differences and the influence of estrogens and androgens
Authors: Asunción-Alvarez Daniel , Palacios Javier , Ybañez-Julca Roberto O. , Rodriguez-Silva Cristhian N. , Nwokocha Chukwuemeka , Cifuentes Fredi , Greensmith David J.
Published: February 2024

Calcium signaling in vascular endothelial cells (ECs) and smooth muscle cells (VSMCs) is essential for the regulation of vascular tone. However, the changes to intracellular Ca2+ concentrations are often influenced by sex differences. Furthermore, a large body of evidence shows that sex hormone imbalance leads to dysregulation of Ca2+ signaling and this is a key factor in the pathogenesis of cardiovascular diseases. In this review, the effects of estrogens and androgens on vascular calcium-handling proteins are discussed, with emphasis on the associated genomic or nongenomic molecular mechanisms. The experimental models from which data were collected were also considered. The review highlights 1) in female ECs, transient receptor potential vanilloid 4 (TRPV4) and mitochondrial Ca2+ uniporter (MCU) enhance Ca2+-dependent nitric oxide (NO) generation. In males, only transient receptor potential canonical 3 (TRPC3) plays a fundamental role in this effect. 2) Female VSMCs have lower cytosolic Ca2+ levels than males due to differences in the activity and expression of stromal interaction molecule 1 (STIM1), calcium release-activated calcium modulator 1 (Orai1), calcium voltage-gated channel subunit-α1C (CaV1.2), Na+-K+-2Cl− symporter (NKCC1), and the Na+/K+-ATPase. 3) When compared with androgens, the influence of estrogens on Ca2+ homeostasis, vascular tone, and incidence of vascular disease is better documented. 4) Many studies use supraphysiological concentrations of sex hormones, which may limit the physiological relevance of outcomes. 5) Sex-dependent differences in Ca2+ signaling mean both sexes ought to be included in experimental design.
Deletion of DWORF does not affect cardiac function in aging and in PLN-R14del cardiomyopathy
Authors: Stege Nienke M. , Oliveira Nunes Teixeira Vivian , Zijlstra Sietske N. , Feringa Anna M. , de Boer Rudolf A. , Silljé Herman H. W.
Published: February 2024

Although DWORF overexpression significantly delayed heart failure development and strongly prolonged life span in PLN-R14del mice, the current study shows that deletion of DWORF does not accelerate or exacerbate PLN-R14del cardiomyopathy in mice harboring the pathogenic R14del allele. In addition, DWORF appears to be dispensable for cardiac function during aging. Changes in DWORF gene expression are therefore unlikely to contribute to the clinical heterogeneity observed in patients with PLN-R14del cardiomyopathy.
Selenium-Containing Protein from Selenium-Enriched Spirulina platensis Relieves Osteoporosis by Inhibiting Inflammatory Response, Osteoblast Inactivation, and Osteoclastogenesis
Authors: Yang Yong , Yang Hong , Feng Xiaotong , Song Qile , Cui Jie , Hou Yajun , Fu Xiaoyan , Pei Yechun
Published: February 2024

Osteoporosis (OP) is a systemic bone disease with loss of bone mass and destruction of the microscopic structure. Many antiosteoporosis drugs have been used for OP therapy, but the therapeutic efficiency remains limited. Therefore, there is an urgent need to develop new drugs for antiosteoporosis treatment. Selenium (Se) is one kind of essential trace element for humans and displays pivotal roles in maintaining bone homeostasis. However, the modulation roles of Se are greatly affected by its chemical forms. Herein, Se containing protein derived from Se-enriched Spirulina platensis (Se-SP) were extracted and used for the treatment of OP in an ovariectomized mice model. The results showed that Se-SP showed enhanced potential in promoting excretion of calcium and alkaline phosphatase (ALP) expression than that of SP in MC3T3-E1 cells. Micro-CT revealed that Se-SP administration in vivo effectively alleviated bone loss as indicated by the upregulated BV, Tb.Th, Bv/TV, Tb.N, and BMD as well as the decreased Tb.Sp. Se-SP in vivo also significantly suppressed inflammatory response through restricting the expression of proinflammatory cytokines expression and upregulating the secretion of anti-inflammatory cytokines. Additionally, Se-SP effectively inhibited ovariectomy-induced osteoblast inactivation and osteoclastogenesis by upregulating BMP2, RUNX2, COL-I, OCN and OPG pression and downregulating RANKL expression. Together, these findings suggested that Se-SP was a new form of Se in therapy of human OP.
A Physics‐Informed Neural Network for the Nonlinear Damage Identification in a Reinforced Concrete Bridge Pier Using Seismic Responses
Authors: Yamaguchi Takahiro , Mizutani Tsukasa
Published: February 2024

The condition assessment of reinforced concrete (RC) bridge piers after an earthquake using measured responses is important for ensuring the safety of road and railway users. The problem is nonlinear, and the locations and extents of damages are various. However, previous research works focused on linear structural identification or model updating assuming a limited number of nonlinear materials for reasonable estimates. Leveraging the ability of deep learning (DL) for robustly estimating a large number of unknown parameters, this study proposes an ALL nonlinear spring multi‐degree‐of‐freedom (MDOF) damage identification algorithm based on a physics‐informed neural network (PINN). The algorithm is applied to a stacked bilinear rotational spring and damper model of a pier. The number of unknown parameters reaches about 50. The errors of estimated elastic stiffnesses, damping coefficients, and ductility factors (DFs) using simulated responses added with noises are 0.4%, 0.6%, and 3.1%, respectively. Using full‐scale RC bridge pier shaking table experiments, the algorithm revealed the distributions of elastic stiffnesses and DFs along the pier height and their deteriorations. The effects of different types of local damages are quantitatively evaluated and visualized on the distributions.
Characterisation of a LINE-1 Insertion in the RP1 Gene by Targeted Adaptive Nanopore Sequencing in a Family with Retinitis Pigmentosa
Authors: Backlund Michael P. , Repo Pauliina , Kangas Harri , Donner Kati , Sankila Eeva-Marja , Krootila Julia , Paavo Maarjaliis , Wartiovaara Kirmo , Kivelä Tero T. , Turunen Joni A.
Published: February 2024

Retinitis pigmentosa (RP) is a group of inherited degenerative retinal disorders affecting more than 1.5 million people worldwide. For 30-50% of individuals with RP, the genetic cause remains unresolved by current clinical diagnostic gene panels. It is likely explained by variants in novel RP-associated genes or noncoding regulatory regions, or by complex genetic alterations such as large structural variants. Recent developments in long-read sequencing techniques have opened an opportunity for efficient analysis of complex genetic variants. We analysed a Finnish family with dominantly inherited RP affecting six individuals in three generations. Two affected individuals underwent a comprehensive clinical examination in combination with a clinical diagnostic gene panel, followed by whole exome sequencing in our laboratory. They exhibited typical signs of RP, yet initial sequence analysis found no causative variants. Reanalysis of the sequencing data detected a LINE-1 (L1) retrotransposon insertion of unknown size in exon 4 of the RP1 axonemal microtubule-associated (RP1) gene. The large chimeric L1 insertion that segregated with the disease was further characterised using targeted adaptive nanopore sequencing of RP1, allowing us to identify a 5.6 kb L1 transposable element insertion in RP1 as the cause of RP in this family with dominantly inherited RP.
A Comparative Analysis of Morphological Characteristics between Endangered Local Prickly Pear and the Newly Introduced Dactylopius opuntiae-Resistant Species in Eastern Morocco
Authors: Marhri Ahmed , Boumediene Mehdi , Tikent Aziz , Melhaoui Reda , Jdaini Kawtar , Mihamou Aatika , Serghini-Caid Hana , Elamrani Ahmed , Hano Christophe , Abid Malika , Addi Mohamed
Published: February 2024

Prickly pear serves as a significant source of income for farmers worldwide, with production taking place in temperate, subtropical, and cold regions. The objective of the present investigation is to explore the morphological parameters of Opuntia robusta and Opuntia dillenii which are resistant to the white cochineal (Dactylopius opuntiae), as well as the local prickly pear that is currently threatened with extinction. This investigation aims to evaluate the feasibility of replacing the endangered local prickly pear with the recently introduced species O. robusta and O. dillenii. This analysis is based on a comprehensive assessment of 26 qualitative and 25 quantitative traits pertaining to cladodes and fruits. In terms of species differentiation and the selection of discriminative features, this study demonstrates the effectiveness of various statistical methods, as well as the analysis carried out according to the descriptors recommended by the International Union for the Protection of New Varieties of Plants (UPOV). Of the 51 parameters evaluated, 13 qualitative and 23 quantitative characters are significant in differentiating the species under study. This underscores the importance of quantitative traits in distinguishing different prickly pear species. Furthermore, color is identified as a crucial characteristic for discriminating between the studied samples. O. robusta is characterized by its high fruit weight, large size, greater pulp content, and high pulp-to-peel ratio, all of which are desirable traits for fresh consumption. Additionally, O. robusta has the highest number of fully developed seeds, making it an attractive option for use in the cosmetic industry. This characteristic renders the O. robusta a potential substitute for the endangered ecotype . However, O. robusta is distinguished by its short stalk, which poses a challenge for fruit harvesting and leaves it susceptible to physical damage and quality loss. Conversely, O. dillenii displays a low pulp content, which serves as a critical indicator of fruit quality. The only desirable agronomic trait of this species is its elevated seed content, which has the potential for utilization in oil production for the cosmetic industry.
A Systematic Review of Blockchain Technology Assisted with Artificial Intelligence Technology for Networks and Communication Systems
Authors: Kumar Kamal , Kumar Vinod , Seema  , Sharma Mukesh Kumar , Khan Akber Ali , Idrisi M. Javed
Published: February 2024

Blockchain is a very secure, authentic, and distributed technology and is very prominent in areas such as edge computation, cloud computation, and Internet-of-things. Artificial intelligence assists in the completion of activities efficiently and effectively by providing intelligence, analytics, and predicting capabilities. There is an obvious convergence between the two technologies. Artificial intelligence systems can utilize blockchain to establish trust in communication channels, ensuring that messages are securely transmitted and received without the need for a centralized intermediary. By leveraging blockchain, artificial intelligence systems can maintain an immutable record of communications, ensuring transparency and preventing unauthorized modifications. The integration of blockchain and artificial intelligence technologies can enhance the security, transparency, and privacy of communication systems. By leveraging blockchain’s decentralized nature and artificial intelligence’s analytical capabilities, secure and trustworthy communication channels can be established, benefiting various domains such as finance, healthcare, and supply chain. Overall, the integration of blockchain and artificial intelligence has the potential to offer several benefits, and as these technologies continue to evolve, new and innovative applications will continue to emerge.
Th17 Cells Secrete TWEAK to Trigger Epithelial–Mesenchymal Transition and Promote Colorectal Cancer Liver Metastasis
Authors: Liu Xin , Wang Xin , Yang Qingxia , Luo Li , Liu Ziqin , Ren Xiaoxue , Lei Kai , Li Shangru , Xie Zonglin , Zheng Gaomin , Zhang Yifan , Hao Yijie , Zhou Qianying , Hou Yingdong , Fang Fei , Song Wu , Cui Ji , Ma Jinping , Xie Wenxuan , Shen Shunli , Tang Ce , Peng Sui , Yu Jun , Kuang Ming , Song Xinming , Wang Fang , Xu Lixia
Published: February 2024

Liver metastasis is the leading cause of mortality in patients with colorectal cancer. Given the significance of both epithelial–mesenchymal transition (EMT) of tumor cells and the immune microenvironment in colorectal cancer liver metastasis (CRLM), the interplay between them could hold the key for developing improved treatment options. We employed multiomics analysis of 130 samples from 18 patients with synchronous CRLM integrated with external datasets to comprehensively evaluate the interaction between immune cells and EMT of tumor cells in liver metastasis. Single-cell RNA sequencing analysis revealed distinct distributions of nonmalignant cells between primary tumors from patients with metastatic colorectal cancer (mCRC) and non-metastatic colorectal cancer, showing that Th17 cells were predominantly enriched in the primary lesion of mCRC. TWEAK, a cytokine secreted by Th17 cells, promoted EMT by binding to receptor Fn14 on tumor cells, and the TWEAK–Fn14 interaction enhanced tumor migration and invasion. In mouse models, targeting Fn14 using CRISPR-induced knockout or lipid nanoparticle–encapsulated siRNA alleviated metastasis and prolonged survival. Mice lacking Il17a or Tnfsf12 (encoding TWEAK) exhibited fewer metastases compared with wild-type mice, while cotransfer of Th17 with tumor cells promoted liver metastasis. Higher TWEAK expression was associated with a worse prognosis in patients with colorectal cancer. In addition, CD163L1+ macrophages interacted with Th17 cells, recruiting Th17 via the CCL4-CCR5 axis. Collectively, this study unveils the role of immune cells in the EMT process and identifies TWEAK secreted by Th17 as a driver of CRLM.

Significance:

TWEAK secreted by Th17 cells promotes EMT by binding to Fn14 on colorectal cancer cells, suggesting that blocking the TWEAK–Fn14 interaction may be a promising therapeutic approach to inhibit liver metastasis.
Breast Cancer Stem Cells Secrete MIF to Mediate Tumor Metabolic Reprogramming That Drives Immune Evasion
Authors: Yan Linlin , Wu Mingming , Wang Tianyu , Yuan Hui , Zhang Xiao , Zhang Huafeng , Li Tao , Pandey Vijay , Han Xinghua , Lobie Peter E. , Zhu Tao
Published: February 2024

Reprogramming of energy metabolism exerts pivotal functions in cancer progression and immune surveillance. Identification of the mechanisms mediating metabolic changes in cancer may lead to improved strategies to suppress tumor growth and stimulate antitumor immunity. Here, it was observed that the secretomes of hypoxic breast cancer cells and breast cancer stem cells (BCSC) induced reprogramming of metabolic pathways, particularly glycolysis, in normoxic breast cancer cells. Screening of the BCSC secretome identified MIF as a pivotal factor potentiating glycolysis. Mechanistically, MIF increased c-MYC–mediated transcriptional upregulation of the glycolytic enzyme aldolase C by activating WNT/β-catenin signaling. Targeting MIF attenuated glycolysis and impaired xenograft growth and metastasis. MIF depletion in breast cancer cells also augmented intratumoral cytolytic CD8+ T cells and proinflammatory macrophages while decreasing regulatory T cells and tumor-associated neutrophils in the tumor microenvironment. Consequently, targeting MIF improved the therapeutic efficacy of immune checkpoint blockade in triple-negative breast cancer. Collectively, this study proposes MIF as an attractive therapeutic target to circumvent metabolic reprogramming and immunosuppression in breast cancer.

Significance:

MIF secreted by breast cancer stem cells induces metabolic reprogramming in bulk tumor cells and engenders an immunosuppressive microenvironment, identifying MIF targeting as a strategy to improve immunotherapy efficacy in breast cancer.
ROR2/Wnt5a Signaling Regulates Directional Cell Migration and Early Tumor Cell Invasion in Ovarian Cancer
Authors: Grither Whitney R. , Baker Breanna , Morikis Vasilios A. , Ilagan Ma. Xenia G. , Fuh Katherine C. , Longmore Gregory D.
Published: February 2024

Adhesion to and clearance of the mesothelial monolayer are key early events in metastatic seeding of ovarian cancer. ROR2 is a receptor tyrosine kinase that interacts with Wnt5a ligand to activate noncanonical Wnt signaling and has been previously shown to be upregulated in ovarian cancer tissue. However, no prior study has evaluated the mechanistic role of ROR2 in ovarian cancer. Through a cellular high-throughput genetic screen, we independently identified ROR2 as a driver of ovarian tumor cell adhesion and invasion. ROR2 expression in ovarian tumor cells serves to drive directed cell migration preferentially toward areas of high Wnt5a ligand, such as the mesothelial lined omentum. In addition, ROR2 promotes ovarian tumor cell adhesion and clearance of a mesothelial monolayer. Depletion of ROR2, in tumor cells, reduces metastatic tumor burden in a syngeneic model of ovarian cancer. These findings support the role of ROR2 in ovarian tumor cells as a critical factor contributing to the early steps of metastasis. Therapeutic targeting of the ROR2/Wnt5a signaling axis could provide a means of improving treatment for patients with advanced ovarian cancer.

Implications:

This study demonstrates that ROR2 in ovarian cancer cells is important for directed migration to the metastatic niche and provides a potential signaling axis of interest for therapeutic targeting in ovarian cancer.
Estrogen Receptor Mutations as Novel Targets for Immunotherapy in Metastatic Estrogen Receptor–positive Breast Cancer
Authors: Goldberg Jonathan , Qiao Na , Guerriero Jennifer L. , Gross Brett , Meneksedag Yagiz , Lu Yoshimi F. , Philips Anne V. , Rahman Tasnim , Meric-Bernstam Funda , Roszik Jason , Chen Ken , Jeselsohn Rinath , Tolaney Sara M. , Peoples George E. , Alatrash Gheath , Mittendorf Elizabeth A.
Published: February 2024

Estrogen receptor–positive (ER+) breast cancer is not considered immunogenic and, to date, has been proven resistant to immunotherapy. Endocrine therapy remains the cornerstone of treatment for ER+ breast cancers. However, constitutively activating mutations in the estrogen receptor alpha (ESR1) gene can emerge during treatment, rendering tumors resistant to endocrine therapy. Although these mutations represent a pathway of resistance, they also represent a potential source of neoepitopes that can be targeted by immunotherapy. In this study, we investigated ESR1 mutations as novel targets for breast cancer immunotherapy. Using machine learning algorithms, we identified ESR1-derived peptides predicted to form stable complexes with HLA-A*0201. We then validated the binding affinity and stability of the top predicted peptides through in vitro binding and dissociation assays and showed that these peptides bind HLA-A*0201 with high affinity and stability. Using tetramer assays, we confirmed the presence and expansion potential of antigen-specific CTLs from healthy female donors. Finally, using in vitro cytotoxicity assays, we showed the lysis of peptide-pulsed targets and breast cancer cells expressing common ESR1 mutations by expanded antigen-specific CTLs. Ultimately, we identified five peptides derived from the three most common ESR1 mutations (D538G, Y537S, and E380Q) and their associated wild-type peptides, which were the most immunogenic. Overall, these data confirm the immunogenicity of epitopes derived from ESR1 and highlight the potential of these peptides to be targeted by novel immunotherapy strategies.

Significance:

Estrogen receptor (ESR1) mutations have emerged as a key factor in endocrine therapy resistance. We identified and validated five novel, immunogenic ESR1-derived peptides that could be targeted through vaccine-based immunotherapy.
NRF2 Activation in Trp53;p16-deficient Mice Drives Oral Squamous Cell Carcinoma
Authors: Hamad Samera H. , Sellers Rani S. , Wamsley Nathan , Zolkind Paul , Schrank Travis P. , Major Michael B. , Weissman Bernard E.
Published: February 2024

Aberrant activation of the NRF2/NFE2L2 transcription factor commonly occurs in head and neck squamous cell carcinomas (HNSCC). Mouse model studies have shown that NRF2 activation alone does not result in cancer. When combined with classic oncogenes and at the right dose, NRF2 activation promotes tumor initiation and progression. Here we deleted the tumor suppressor genes p16INK4A and p53 (referred to as CP mice), which are commonly lost in human HNSCC, in the presence of a constitutively active NRF2E79Q mutant (CPN mice). NRF2E79Q expression in CPN mice resulted in squamous cell hyperplasia or dysplasia with hyperkeratosis in the esophagus, oropharynx, and forestomach. In addition, CPN mice displayed oral cavity squamous cell carcinoma (OSCC); CP mice bearing wild-type NRF2 expression did not develop oral cavity hyperplasia, dysplasia or OSCC. In both CP and CPN mice, we also observed predominantly abdominal sarcomas and carcinomas. Our data show that in the context of p53 and p16 tumor suppressor loss, NRF2 activation serves oncogenic functions to drive OSCC. CPN mice represent a new model for OSCC that closely reflects the genetics of human HNSCC.

Significance:

Human squamous cancers frequently show constitutive NRF2 activation, associated with poorer outcomes and resistance to multiple therapies. Here, we report the first activated NRF2-driven and human-relevant mouse model of squamous cell carcinoma that develops in the background of p16 and p53 loss. The availability of this model will lead to a clearer understanding of how NRF2 contributes to the initiation, progression, and therapeutic response of OSCC.
Increase of Phosphoprotein Expressions in Amotosalen/UVA-Treated Platelet Concentrates
Authors: Muret Charlotte , Crettaz David , Alberio Lorenzo , Prudent Michel
Published: February 2024

Background: Pathogen inactivation treatment (PIT) has been shown to alter platelet function, phenotype, morphology and to induce a faster aging of platelet concentrates (PCs). Key pieces of information are still missing to understand the impacts of PITs at the cellular level. Objectives: This study investigated the impact of amotosalen/UVA on PCs, from a post-translational modifications (PTM) point of view. Phosphoproteomic analyses were conducted on resting platelets, right after the amotosalen/UVA treatment and compared with untreated PCs. Method: A two-arm study setting was carried out to compare PIT (amotosalen/UVA) to untreated PCs, on day 1 post-donation. Based on a pool-and-split approach, 12 PCs were split into two groups (treated and untreated). Quantitative phosphoproteomics was performed using TMT technology to study the changes of phosphoproteins right after the PIT. Results: A total of 3,906 proteins and 7,334 phosphosites were identified, and 2,473 proteins and 2,214 phosphosites were observed in at least 5 to 6 replicates. Compared to untreated platelets, PIT platelets exhibited an upregulation of the phosphorylation effects, with 109 phosphosites identified with a higher than 2-fold change. Two pathways were clearly identified. The mitogen activated protein kinases (MAPKs) cascade, which triggers the granule secretion and the activation of the pS15 HSPB1. One of the shape change pathways was also observed with the inhibition of the Threonine 18 and Serine 19 phosphorylations on myosin light chain (MLC) protein after the amotosalen/UVA treatment. Conclusions: This work provides a deep insight into the impact of amotosalen/UVA treatment from a phosphoprotein viewpoint on resting platelets. Clear changes in phosphorylation of proteins belonging to different platelet pathways were quantified. This discovery corroborates previous findings and fills missing parts of the effect of photochemical treatments on platelets.
Sertraline Promotes Health and Longevity in Caenorhabditis elegans
Authors: Liang Yu , Zhou Yiming , Zhou Can , Cai Xinqi , Liu Li , Wei Fang , Li Guolin
Published: February 2024

Introduction: While several antidepressants have been identified as potential geroprotectors, the effect and mechanism of sertraline on healthspan remain to be elucidated. Here, we explored the role of sertraline in the lifespan and healthspan of Caenorhabditis elegans. Methods: The optimal effect concentration of sertraline was first screened in wild-type N2 worms under heat stress conditions. Then, we examined the effects of sertraline on lifespan, reproduction, lipofuscin accumulation, mobility, and stress resistance. Finally, the expression of serotonin signaling and aging-related genes was investigated to explore the underlying mechanism, and the lifespan assays were performed in ser-7 RNAi strain, daf-2, daf-16, and aak-2 mutants. Results: Sertraline extended the lifespan in C. elegans with concomitant extension of healthspan as indicated by increasing mobility and reducing fertility and lipofuscin accumulation, as well as enhanced resistance to different abiotic stresses. Mechanistically, ser-7 orchestrated sertraline-induced longevity via the regulation of insulin and AMPK pathways, and sertraline-induced lifespan extension in nematodes was abolished in ser-7 RNAi strain, daf-2, daf-16, and aak-2 mutants. Conclusion: Sertraline promotes health and longevity in C. elegans through ser-7-insulin/AMPK pathways.
Transient Myopia and Ciliochoroidal Effusion following Influenza Vaccination
Authors: Ghanbarnia Mohammad Javad , Rahimnezhad Nazanin , Nilforushan Naveed
Published: February 2024

Introduction: The aim of the study was to report a case of ocular adverse events following influenza vaccination which involved bilateral myopic shift, ciliochoroidal effusion, and fine retinal folds in a middle-aged woman. Case Presentation: A 42-year-old female presented with sudden-onset painless binocular decreased distance vision. She had received a quadrivalent influenza vaccine (Influvac Tetra) injection 10 days prior, a few days after which she experienced blurred vision. Her initial uncorrected visual acuity and refraction were 20/200 and −3.00/−1.00 × 180 in the right eye, 20/100 and −3.00/−0.50 × 50 in the left eye. Intraocular pressure was within normal limits bilaterally. Anterior segment examination was significant for bilateral shallow anterior chambers (AC) and narrow iridocorneal angles with no cells or flare. Fundus examination was notable for bilateral fine chorioretinal folds radiating from the macula and bilateral low-lying choroidal effusion in the far periphery. Ultrasound biomicroscopy confirmed bilateral ciliochoroidal effusions, shallow AC, and anterior rotation of the ciliary bodies. The patient was started on oral and topical corticosteroids plus atropine and timolol eye drops after which prompt improvement was observed. Restoration of visual acuity and complete resolution of the symptoms without any further complication were observed after 2 weeks. Conclusion: The temporal association between the onset of the patient’s symptoms and influenza vaccination, in the absence of any pertinent medical conditions or medications, significantly implicates causality. Future research and case reports can help in corroborating this ocular adverse event attributed to influenza vaccination.
Use of Inotropic Agents in Advanced Heart Failure: Pros and Cons
Authors: Hansen Benjamin Lautrup , Kristensen Søren Lund , Gustafsson Finn
Published: February 2024

Background: Use of inotropic agents in advanced heart failure (HF) has over time been evaluated in several randomized, controlled clinical trials (RCTs). However, the evidence for both efficacy and safety is conflicting. Summary: In this narrative review, the evidence for and role of inotropes in advanced HF are outlined. Readers are provided with a comprehensive overview of key-findings from 23 important RCTs comparing orally or intravenously administered inotropes. Clinically relevant pros and cons of inotropic regimens are summarized to guide the clinician in the management of advanced HF patients in different settings (e.g., out-patient, in-patient, and intensive care unit). Finally, future perspectives and potential new agents are discussed. Key Messages: Long-term use of inotropes in advanced HF is controversial and should only be considered in selected patients (e.g., as palliative or bridging strategy). However, short-term use continues to play a large role in hospitalized patients with cardiogenic shock or severe decompensated acute HF.
Adverse Effects of Do-It-Yourself Nail Cosmetics: A Literature Review
Authors: Wang Elise , Lipner Shari R.
Published: February 2024

Background: As self-applied manicures have gained popularity, it is important for physicians to remain informed about potential associated side effects. Traditional polish remains most popular among nail enthusiasts, but the pursuit of durability and convenience accelerated development of other nail cosmetic products, including gel polish, acrylic nails, and press-on nails. Despite documented adverse effects among beauty professionals and salon customers, individuals practicing at-home nail care routines may face similar, if not more, frequent complications due to misinformation, inadequate training, and social media trends. Summary: This review provides an overview of adverse effects associated with different at-home nail cosmetics. Allergic contact dermatitis is the most prevalent adverse event, primarily attributed to (meth)acrylates found in nail glue, gel polish, and acrylic nails. Other adverse effects include infections, chemical burns, and complications from ultraviolet nail lamps. Key Message: The review highlights the importance of transparent product labeling and appropriate warning labels from manufacturers, as well as physician education and awareness for minimizing risks related to at-home nail cosmetic applications.
The Phylotypic Brain of Vertebrates, from Neural Tube Closure to Brain Diversification
Authors: Senovilla-Ganzo Rodrigo , García-Moreno Fernando
Published: February 2024

Background: The phylotypic or intermediate stages are thought to be the most evolutionary conserved stages throughout embryonic development. The contrast with divergent early and later stages derived from the concept of the evo-devo hourglass model. Nonetheless, this developmental constraint has been studied as a whole embryo process, not at organ level. In this review, we explore brain development to assess the existence of an equivalent brain developmental hourglass. In the specific case of vertebrates, we propose to split the brain developmental stages into: (1) Early: Neurulation, when the neural tube arises after gastrulation. (2) Intermediate: Brain patterning and segmentation, when the neuromere identities are established. (3) Late: Neurogenesis and maturation, the stages when the neurons acquire their functionality. Moreover, we extend this analysis to other chordates brain development to unravel the evolutionary origin of this evo-devo constraint. Summary: Based on the existing literature, we hypothesise that a major conservation of the phylotypic brain might be due to the pleiotropy of the inductive regulatory networks, which are predominantly expressed at this stage. In turn, earlier stages such as neurulation are rather mechanical processes, whose regulatory networks seem to adapt to environment or maternal geometries. The later stages are also controlled by inductive regulatory networks, but their effector genes are mostly tissue-specific and functional, allowing diverse developmental programs to generate current brain diversity. Nonetheless, all stages of the hourglass are highly interconnected: divergent neurulation must have a vertebrate shared end product to reproduce the vertebrate phylotypic brain, and the boundaries and transcription factor code established during the highly conserved patterning will set the bauplan for the specialised and diversified adult brain. Key Messages: The vertebrate brain is conserved at phylotypic stages, but the highly conserved mechanisms that occur during these brain mid-development stages (Inducing Regulatory Networks) are also present during other stages. Oppositely, other processes as cell interactions and functional neuronal genes are more diverse and majoritarian in early and late stages of development, respectively. These phenomena create an hourglass of transcriptomic diversity during embryonic development and evolution, with a really conserved bottleneck that set the bauplan for the adult brain around the phylotypic stage.
Response inhibition in premotor cortex corresponds to a complex reshuffle of the mesoscopic information network
Authors: Bardella Giampiero , Giuffrida Valentina , Giarrocco Franco , Brunamonti Emiliano , Pani Pierpaolo , Ferraina Stefano
Published: February 2024

Recent studies have explored functional and effective neural networks in animal models; however, the dynamics of information propagation among functional modules under cognitive control remain largely unknown. Here, we addressed the issue using transfer entropy and graph theory methods on mesoscopic neural activities recorded in the dorsal premotor cortex of rhesus monkeys. We focused our study on the decision time of a Stop-signal task, looking for patterns in the network configuration that could influence motor plan maturation when the Stop signal is provided. When comparing trials with successful inhibition to those with generated movement, the nodes of the network resulted organized into four clusters, hierarchically arranged, and distinctly involved in information transfer. Interestingly, the hierarchies and the strength of information transmission between clusters varied throughout the task, distinguishing between generated movements and canceled ones and corresponding to measurable levels of network complexity. Our results suggest a putative mechanism for motor inhibition in premotor cortex: a topological reshuffle of the information exchanged among ensembles of neurons.
The Transgression List in Šurpu Tablet IV and Its Sordid Moral Implications
Authors: Feder Yitzhaq
Published: February 2024

Modern scholarship has become more attentive to the interrelation between performative and scholastic factors in the production of ancient Near Eastern ritual texts. This article aims to shed light on the compositional processes responsible for the integration of a list of transgressions into Šurpu Tablet 4. This analysis is facilitated by the identification of a close parallel from the Namerimburruda tradition. The comparison of these texts illuminates the subtle manner by which scribe responsible for Šurpu IV appropriated earlier materials to fit the theological and rhetorical aims of the new composition. This focused case study can serve as a point of departure for further research on the flexible roles of interpolated sin lists in ancient Near Eastern literature.
Predictive Modelling in Underwater Archaeology. A Case Based on Mesolithic Coastal Settlements in Denmark
Authors: Giatsiatsou Paschalina
Published: February 2024

Research on underwater archaeological sites has been adversely affected by various socioeconomic (specialized equipment, lack of know-how, legal framework, etc.) and environmental (weather conditions, site formation processes, etc.) challenges. Interdisciplinary approaches, especially technology integration, can help introduce a methodology to evaluate these factors and mitigate limitations to enhance the information retrieved and assist the interpretation process. One such approach may be predictive modelling while developing methodologies based on predictive models can be assets in research. The work presented in this article is based on this approach and assesses the use of predictive models based on six case studies. It is an effort to evaluate whether targeting sub-areas when excavating on limited time and budget can help clarify the interpretation of the information collected from these areas.
Apollo and Maria: Two 17th-Century Warships Found at Vaxholm, Sweden
Authors: Höglund Patrik , Hansson Jim
Published: February 2024

In October 2019, the wrecks of two warships were found in the inlet to Stockholm. According to historical sources, Vasa’s three so-called sister ships might have been sunk in the area to block off a strait. These large ships were launched in the years 1629–1634 and built by the same master shipbuilder who participated in the construction of Vasa. However, after further archaeological investigations, the two ships were identified as Apollo and Maria, two medium-sized warships launched in 1648. The wrecks shed light on a twenty-year period when ships of this type were prioritized because they were considered more practical and offered more value for money. The ships were heavily constructed and could carry heavy armament for their size. They could be at sea in difficult conditions and be used for a variety of purposes. Despite the fact that the investigations did not match initial hopes of finding Vasa’s sister ships, important results were achieved. In 2021, Äpplet, one of Vasa’s sister ships, was found in the vicinity of Apollo and Maria.
Of Welfare, Sacred Places, and “Rice Christians”: Freedom of Religion and Multiple Religious Belonging
Authors: Erlings Esther
Published: February 2024

When governments are structurally unable to provide social services, or when disaster strikes, relief organisations tend to step in. This is also the case in South and East Asia. Such organisations may be faith-based, leading to the emergence of what Asians colloquially call “rice Christians”: persons who (allegedly) convert to a religion in order to access services, or out of loyalty to the aid-supplying organisation. Such converts may continue to practice their traditional religions and beliefs. This raises the question whether rights to religion or belief are still available to “rice Christians” when governments, e.g., seek to redevelop a sacred site that formed part of their original belief system. The present article addresses that question, drawing upon the concept of multiple religious belonging (‘mrb’) and a 2017 decision of the African Court on Human and Peoples’ Rights in which the court accepted that individuals may adhere to multiple religions, especially where conversion happened within a missionary context and the now-claimed belief is Indigenous or traditional. It argues in favour of recognition of mrb within the context of freedom of religion, which would mean that also “rice Christians” can continue to rely on original belief systems to protect their practices and places.
2. From Images of Italy to Early Russian Art
Authors: Tarasov Oleg
Published: February 2024

This chapter is devoted to work on early icons by the Russian art historian Pavel Muratov (1881–1950), who laid the foundations for their stylistic analysis. Federico Zeri (1921–98) has emphasized the significance of the views of Henri Matisse (1869–1954) on Russian icons, which Matisse encountered when he visited Moscow in 1911. This chapter finds that it was Muratov who continued Matisse’s work in acquainting the Western spectator with the aesthetic of early icons.