bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoantigen vaccine and neoantigen‐specific cell adoptive transfer therapy in solid tumors: Challenges and future directions
Authors: Shen Yanwei , Yu Lu , Xu Xiaoli , Yu Shaojun , Yu Zhuo 
Published: August 2022

AbstractThe phenomenon of tumor hierarchy and genetic instability can be explained by the “two‐hits theory” and results in the occurrence of many somatic mutations. The expression of nonsynonymous mutations results in the production of mutant proteins from tumor cells, namely tumor‐specific antigens called neoantigens. Because neoantigens do not exist in healthy cells, they have the potential to stimulate antitumor immune responses by CD4+ and CD8+ T‐cell activation without jeopardizing normal tissues. Immunotherapy has reshaped the cancer treatment paradigm in recent decades with the introduction of immune‐checkpoint blockade therapy and transgenic T‐cell receptor/chimeric antigen receptor T cells. However, these strategies performed poorly in solid tumors because of the obstacles of the immunosuppressive microenvironment caused by regulatory T cells and other suppressor cells. Therefore, other immunotherapeutic strategies are under development, such as personalized vaccines, to trigger de novo T‐cell responses against neoantigens and lead to the amplification of tumor‐specific T‐cell subclones. Neoantigen epitope prediction algorithms have enabled the detection of neoantigens and the creation of tailored neoantigen vaccines as a result of the fast development of next‐generation sequencing and cancer bioinformatics. Here we provide an overview of the current neoantigen cancer vaccines and adoptive T‐cell transfer therapy with neoantigen‐specific lymphocytes. We also discuss the challenges in developing neoantigen‐targeted immunotherapeutic strategies for cancer.
COL3A1: Potential prognostic predictor for head and neck cancer based on immune‐microenvironment alternative splicing
Authors: Shen Yuchen , Li Xinyu , Wang Deming , Zhang Liming , Li Xiao , Su Lixin , Fan Xindong , Yang Xitao 
Published: August 2022

AbstractWe aimed to identify a novel prognostic biomarker for head and neck squamous cell carcinoma (HNSCC) based on tumor immunology‐related alternative splicing (AS). Data for 502 HNSCC and 44 normal samples were obtained from the TCGA database and used to establish an AS‐related risk model through univariate, least absolute shrinkage, and selection operator Cox regression analyses. Fresh HNSCC and normal oral tissues were surgically obtained from 44 HNSCC patients. Western blotting and quantitative reverse transcription‐PCR were used to assess gene expression levels. Kaplan–Meier was performed to evaluate patients' overall survival (OS) rate. The CIBERSORT algorithm, single‐sample gene set enrichment analysis, and immune checkpoint analyses were performed to compare immune activities between subgroups. The risk model was established using 10 pivotal AS events first. Collagen Type III Alpha 1 Chain (COL3A1) were screened based on |log2FC| ≥ 1 and FDR < 0.05 criteria. COL3A1 expression levels in HNSCC tissues were elevated relative to normal tissues (p < 0.001). Moreover, COL3A1 was a reliable biomarker for HNSCC patients' prognostic prediction in both cohorts (p < 0.001, p = 0.0085, respectively). COL3A1 protein (p = 0.0054) and mRNA (p < 0.0001) levels were correlated with HNSCC differentiation. Furthermore, the T stage was correlated with COL3A1 expression (p = 0.043), and COL3A1 expression was an independent prognostic predictor for HNSCC patients (p = 0.006). Compared with the risk model, COL3A1 was better at evaluating immune cell infiltrations, immune activities, and immune checkpoint gene expressions of HNSCC lesions.
The GAL/GALR2 axis promotes the perineural invasion of salivary adenoid cystic carcinoma via epithelial‐to‐mesenchymal transition
Authors: Wang Jun , Yang Zihui , Liu Yuanyang , Li Huan , Yang Xiangming , Gao Wanpeng , Zhao Qi , Yang Xinjie , Wei Jianhua 
Published: August 2022

AbstractBackgroundPerineural invasion (PNI) is a typical pathological characteristic of salivary adenoid cystic carcinoma (SACC) and other neurotrophic cancers. The mechanism of the neural microenvironment controlling tumor progression during the PNI process is unclear. In the present study, we investigated the role and molecular mechanisms of nerve‐derived neuropeptide galanin (GAL) and its receptor (GALR2) in the regulation of PNI in SACC.MethodsImmunohistochemistry staining and clinical association studies were performed to analyze the expression of GAL and GALR2 in SACC tissues and their clinical value. Dorsal root ganglion or SH‐SY5Y cells were co‐cultured with SACC cells in vitro to simulate the interactions between the neural microenvironment and tumor cells, and a series of assays including transcriptome sequencing, Western blot, and Transwell were performed to investigate the role and molecular mechanism of GAL and GALR2 in the regulation of SACC cells. Moreover, both the in vitro and in vivo PNI models were established to assess the potential PNI‐specific therapeutic effects by blocking the GAL/GALR2 axis.ResultsGAL and GALR2 were highly expressed in SACC tissues, and were associated with PNI and poor prognosis in SACC patients (p < 0.05). Nerve‐derived GAL activated GALR2 expression in SACC cells and induced epithelial‐to‐mesenchymal transition (EMT) in SACC cells. Adding human recombinant GAL to the co‐culture system promoted the proliferation, migration, and invasion of SACC cells significantly, but inhibited the apoptosis of SACC cells. Adding M871, a specific antagonist of GALR2, significantly blocked the above effects (p < 0.05) and inhibited the PNI of SACC cells in vitro and in vivo (p < 0.05).ConclusionsThis study demonstrated that nerve‐derived GAL activated GALR2 expression, and promoted EMT in SACC cells, thereby enhancing the PNI process. Interruption of the GAL/GALR2 axis might be a novel strategy for anti‐PNI therapy for SACC.
Physicochemical Characterization of a Fern Polysaccharide from Alsophila spinulosa Leaf and Its Anti‐Aging Activity in Caenorhabditis elegans
Authors: Pei Ying‐Hong , Yan Ning‐Ning , Zhang Hui‐Fang , Zhang Shu‐Ting , Tang Zi‐Zhong , Huang Yan , Chen Tao , Feng Shi‐Ling , Ding Chun‐Bang , Yuan Shu , Yuan Ming 
Published: August 2022

AbstractAlsophila spinulosa, as a rare tree fern with potential medicinal value, has attracted extensive attention. Herein, the physicochemical properties, antioxidant and anti‐aging activities of polysaccharide from A. spinulosa leaf (ALP) were investigated. ALP was composed of galactose, arabinose, glucose, rhamnose, galacturonic acid, mannose, and fucose. (1→), (1→6), and (1→2) bond types were the primary glycosidic bond in ALP. Surprisingly, ALP displayed the wonderful activity of antioxidant and anti‐aging, including excellent scavenging ability against DPPH and ABTS radicals in vitro; prolonging the life span, improving activity of antioxidative enzymes (SOD and CAT), and decreasing the level of ROS, MDA in Caenorhabditis elegans. Meanwhile, ALP promoted DAF‐16 to move into the nuclear. Overall, our results illustrated that ALP could be further developed as a functional food ingredient.
An Updated Review on Biologically Promising Natural Oxepines
Authors: Mandal Bhagirath , Karmakar Indrajit , Brahmachari Goutam 
Published: August 2022

AbstractBenzo‐oxepines and dibenzo‐oxepines, a unique class of naturally occurring secondary metabolites, are distributed mainly in plants and fungi and have received much attention from phytochemists and biologists based on their fascinating structural features and health‐promoting functions. This review summarizes 100 oxepine derivatives comprising three categories: benzo‐oxepine, dibenzo‐oxepine, and pyrano‐oxepine. Studies on various structural features and pharmacological activities of oxepine derivatives promote further in‐depth research on these potent natural products. This review portrays the natural occurrence, bioactivity and biosynthesis of oxepines reported from 1984 to 2021.
Overexpression of TRIM32 promotes pancreatic β‐cell autophagic cell death through Akt/mTOR pathway under high glucose conditions
Authors: Wan Tingting , Wang Yidan , Wang Chunxu , Wang Hongjie , Li Xiudan , Li Yanbo 
Published: August 2022

AbstractType 2 diabetes mellitus (T2DM) is a growing worldwide epidemic and is characterized by progressive pancreatic β‐cell dysfunction and insulin resistance. Tripartite motif protein 32 (TRIM32) belongs to the TRIM family protein and has been shown to be involve in insulin resistance in skeletal muscle and the liver. However, the effect of TRIM32 on pancreatic β‐cell dysfunction and its mechanism remains unknown. In the current study, we found that serum TRIM32 concentrations of T2DM in patients were significantly elevated compared to those in healthy controls, which indicated that TRIM32 might be used as a diagnostic biomarker in T2DM patients. In INS‐1 cells, exposure to high glucose (HG) conditions caused a significant elevation in TRIM32 expression and TRIM32 was located in the nucleus. Overexpression of TRIM32 in INS‐1 cells exacerbated the effects of HG‐induced autophagy and impaired insulin secretion. In contrast, the silencing of TRIM32 produced the opposite effect. Furthermore, TRIM32 overexpression decreased the phosphorylation levels of Akt and mTOR under HG conditions. However, the activation of Akt/mTOR by MHY1485 reversed the effects of TRIM32 on HG‐treated INS‐1 cells. Collectively, the present results suggested that TRIM32 participates in the development of T2DM by modulating autophagic cell death and insulin secretion, which might occur through the Akt/mTOR pathway. Thus, TRIM32 might be a promising target in T2DM therapy.
RPRM deletion preserves hematopoietic regeneration by promoting EGFR‐dependent DNA repair and hematopoietic stem cell proliferation post ionizing radiation
Authors: Li Zixuan , Zhou Zhou , Tian Shuaiyu , Zhang Kailu , An Gangli , Zhang Yarui , Ma Renyuxue , Sheng Binjie , Wang Tian , Yang Hongying , Yang Lin 
Published: August 2022

AbstractReprimo (RPRM), a target gene of p53, is a known tumor suppressor. DNA damage induces RPRM, which triggers p53‐dependent G2 arrest by inhibiting cyclin B1/Cdc2 complex activation and promotes DNA damage‐induced apoptosis. RPRM negatively regulates ataxia‐telangiectasia mutated by promoting its nuclear‐cytoplasmic translocation and degradation, thus inhibiting DNA damage. Therefore, RPRM plays a crucial role in DNA damage response. Moreover, the loss of RPRM confers radioresistance in mice, which enables longer survival and less severe intestinal injury after radiation exposure. However, the role of RPRM in radiation‐induced hematopoietic system injury remains unknown. Herein, utilizing a RPRM‐knockout mouse model, we found that RPRM deletion did not affect steady‐state hematopoiesis in mice. However, RPRM knockout significantly alleviated radiation‐induced hematopoietic system injury and preserved mouse hematopoietic regeneration in hematopoietic stem cells (HSCs) against radiation‐induced DNA damage. Further mechanistic studies showed that RPRM loss significantly increased EGFR expression and phosphorylation in HSCs to activate STAT3 and DNA‐PKcs, thus promoting HSC DNA repair and proliferation. These findings reveal the critical role of RPRM in radiation‐induced hematopoietic system injury, confirming our hypothesis that RPRM may serve as a novel target for radiation protection.
Association of N‐terminal pro‐B‐type natriuretic peptide with mortality in elderly (≥80 years) patients undergoing percutaneous coronary intervention
Authors: Sager Raphael , Keller Lukas S. , Stehli Julia , Jakob Philipp , Michel Jonathan , Kasel Markus , Templin Christian , Stähli Barbara E. 
Published: August 2022

AbstractObjectivesThe aim of this study was to determine the role of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) in the prognostication of patients ≥80 years of age undergoing percutaneous coronary intervention (PCI).BackgroundElderly patients with coronary artery disease in need of PCI represent a growing patient population. Advanced risk prediction in this frail and comorbid patient population is important.MethodsA total of 460 consecutive patients ≥80 years of age undergoing PCI for acute (ACS) or chronic coronary syndromes (CCS) at the University Hospital Zurich, Switzerland, between January 2016 and December 2018 and with available baseline NT‐proBNP levels were included in the analysis. Patients were stratified according to baseline NT‐proBNP levels. The primary endpoint was all‐cause mortality at a median follow‐up of 33 (interquartile range: 3–392) days.ResultsMedian baseline NT‐proBNP levels were 1411 (457–3984) ng/L. All‐cause mortality was 7.8% in the lowest and 27.8% in the highest NT‐proBNP quartile group (p < 0.001). In patients with ACS, all‐cause mortality was 4.8% and 30.4% in the lowest and the highest NT‐proBNP quartile (p < 0.001), and corresponding rates in patients with CCS were 11.1% and 22.2% (p = 0.38). In multivariable Cox regression analysis, baseline NT‐proBNP levels were independently associated with an increased risk of all‐cause mortality (adjusted hazard ratio: 1.00, 95% confidence interval: 1.00–1.00,p = 0.04).ConclusionsBaseline NT‐proBNP levels were identified as independent predictor of mortality in elderly (≥80 years) patients undergoing PCI. Hence, baseline NT‐proBNP allows for the identification of a high‐risk elderly patient subset.
Mechanism of BPh3‐Catalyzed N‐Methylation of Amines with CO2 and Phenylsilane: Cooperative Activation of Hydrosilane
Authors: Ratanasak Manussada , Murata Takumi , Adachi Taishin , Hasegawa Jun‐ya , Ema Tadashi 
Published: August 2022

AbstractBPh3 catalyzes the N‐methylation of secondary amines and the C‐methylenation (methylene‐bridge formation between aromatic rings) of N,N‐dimethylanilines or 1‐methylindoles in the presence of CO2 and PhSiH3; these reactions proceed at 30–40 °C under solvent‐free conditions. In contrast, B(C6F5)3 shows little or no activity. 11B NMR spectra suggested the generation of [HBPh3]−. The detailed mechanism of the BPh3‐catalyzed N‐methylation of N‐methylaniline (1) with CO2 and PhSiH3 was studied by using DFT calculations. BPh3 promotes the conversion of two substrates (N‐methylaniline and CO2) into a zwitterionic carbamate to give three‐component species [Ph(Me)(H)N+CO2−⋅⋅⋅BPh3]. The carbamate and BPh3 act as the nucleophile and Lewis acid, respectively, for the activation of PhSiH3 to generate [HBPh3]−, which is used to produce key CO2‐derived species, such as silyl formate and bis(silyl)acetal, essential for the N‐methylation of 1. DFT calculations also suggested other mechanisms involving water for the generation of [HBPh3]− species.
A Web Tool for Calculating Substituent Descriptors Compatible with Hammett Sigma Constants**
Authors: Ertl Peter 
Published: August 2022

AbstractThe electron‐donating and ‐accepting power of organic substituents is an important parameter affecting many properties of parent molecules, most notably their reactivity and pKa of ionisable groups. These substituent properties are described by Hammett σ constants obtained by measuring ionization constants of substituted benzoic acids. Although values of the Hammett σ constants have been measured for the most common functional groups, data for many important substituents are not available. In the present study, a method to calculate substituent descriptors compatible with the Hammett σ constants using quantum‐chemically derived parameters is described. On this basis, a free web tool allowing to calculate electronic and hydrophobic substituent descriptors is made available at https://bitly.com/getsigmas.
Corporate social responsibility (CSR) performance and stakeholder engagement: Evidence from the quantity and quality of CSR disclosures
Authors: Koh Kevin , Li Heather , Tong Yen H. 
Published: August 2022

AbstractWith increasing stakeholders' demand for information on corporate social responsibility (CSR) performance and a growing number of firms issuing standalone CSR reports, this study examines the relation between CSR performance and the quantity and quality of CSR disclosures. Drawing on signaling and political legitimacy theories of information disclosure and using a US sample of 2774 standalone CSR reports from 2003 to 2015, we find better CSR performing firms issue longer CSR reports and provide incremental information in their CSR reports relative to their annual financial reports. Furthermore, the textual content in their CSR reports is less focused on short‐term issues, reflecting higher disclosure quality. In contrast, poor CSR performing firms tend exhibit lower disclosure quality as their CSR reports use more uncertain words. Our study contributes to the understanding of how CSR performance affect stakeholder engagement through the characteristics of textual content in standalone CSR reports.
Design of an automatic gain control loop for high speed communication
Authors: Chowdhury Sujan , Hasan Mehedi 
Published: August 2022

AbstractThis paper presents the design of an automatic gain control (AGC) loop for high‐speed communication systems, which can be used in wired, wireless, or optical receiver. The design is performed in 130 nm SiGe BiCMOS technology. A Gilbert cell‐based variable gain amplifier is designed, which shows approximately linear gain control with respect to the gain control voltage. The variable gain amplifier is followed by two fixed gain cascode amplifiers. Then, a full wave rectifier‐based peak detector is designed and analyzed. To reduce the peak detector error, a compensation technique is applied. Finally, an operational amplifier is designed, which is used as voltage adder and comparator. The designed AGC loop is simulated with sinusoidal and pseudorandom binary sequence (prbs) input signal with high frequency signal of 1 to 30 GHz. The simulation results of the AGC loop show that a gain tuning range of 47 dB (−7 to 40 dB) is obtained in this design. It is also seen that the reference signal can be varied from 50 to 200 mV. This AGC works in the input voltage signal range between 3 mV peak and 230 mV peak, and the power dissipation of is 79 mW.
Generalized network psychometrics of eating‐disorder psychopathology
Authors: Forbush Kelsie T. , Swanson Trevor J. , Chen Yiyang , Siew Cynthia S. Q. , Hagan Kelsey E. , Chapa Danielle A. N. , Tregarthen Jenna , Wildes Jennifer E. , Christensen Kara A. 
Published: August 2022

AbstractObjectiveAs network models of eating disorder (ED) psychopathology become increasingly popular in modeling symptom interconnectedness and identifying potential treatment targets, it is necessary to contextualize their performance against other methods of modeling ED psychopathology and to evaluate potential ways to optimize and capitalize on their use. To accomplish these goals, we used generalized network psychometrics to estimate and compare latent variable models and network models, as well as hybrid models.MethodWe tested the structure of the Eating Pathology Symptoms Inventory (EPSI) and Eating Disorder Examination‐Questionnaire (EDE‐Q) in Recovery Record, Inc. mobile phone application users (N = 6856).ResultsAlthough all models fit well, results favored a hybrid latent variable and network framework, which showed that ED symptoms fit best when modeled as higher‐order constructs, rather than direct symptom‐to‐symptom connections, and when the relationships between those constructs are described as a network. Hybrid models in which latent factors were modeled as nodes within a network showed that EPSI Purging, Binge Eating, Cognitive Restraint, Body Dissatisfaction, and Excessive Exercise had high importance in the network. EDE‐Q Eating Concern and Shape Concern were also important nodes. Results showed that the EPSI network was highly stable and replicable, whereas the EDE‐Q network was not.DiscussionIntegrating latent variable and network model frameworks enables tests of centrality to identify important latent variables, such as purging, that may promote the spread of ED psychopathology throughout a network, allowing for the identification of future treatment targets.
Habitat selection in a fluctuating ground squirrel population: Density‐dependence and fitness consequences
Authors: Aliperti Jaclyn R. , Jenderseck Kimberly , Van Vuren Dirk H. 
Published: August 2022

AbstractInvestigating individual‐based habitat settlement decisions is a central theme in ecology, yet studies that quantify density‐dependent habitat selection or tie fitness to resource selection decisions remain rare. We quantified habitat selection in golden‐mantled ground squirrels (Callospermophilus lateralis) across two spatial scales (home‐range placement, and occurrence within the home range) by using 11 consecutive years of data on individual space use, and we used resource selection functions and multilevel modeling to address how habitat preferences may be influenced by density or linked to fitness outcomes. Squirrels preferred dry meadow over other habitat types (wet meadow, aspen, spruce, and willow) at both spatial scales. Squirrels were more likely to use dry meadow that contained shorter vegetation and vision‐enhancing prominences such as rocks (“perches”). The use of dry meadow at each scale was not influenced by changes in density. The use of dry meadow did not lead to increased litter size, pre‐hibernation mass, or survival. However, squirrels that experienced a greater number of perches or lower local densities had higher survival rates. Our results suggest that a lack of visual obstruction, probably facilitating detection of predators, drives habitat selection in this system. Surprisingly, squirrels maintained their preference for dry meadow as density increased, and they experienced reduced survival as a result. This work furthers our understanding about the causes and consequences of changes in habitat use, informing wildlife management and conservation.
Practical management of frailty in older patients with heart failure
Authors: Boureau Anne‐Sophie , Annweiler Cédric , Belmin Joël , Bouleti Claire , Chacornac Mathieu , Chuzeville Michel , David Jean‐Philippe , Jourdain Patrick , Krolak‐Salmon Pierre , Lamblin Nicolas , Paccalin Marc , Sebbag Laurent , Hanon Olivier 
Published: August 2022

AbstractAimsThe heart failure (HF) prognosis in older patients remains poor with a high 5‐years mortality rate more frequently attributed to noncardiovascular causes. The complex interplay between frailty and heart failure contribute to poor health outcomes of older adults with HF independently of ejection fraction. The aim of this position paper is to propose a practical management of frailty in older patients with heart failure.MethodsA panel of multidisciplinary experts on behalf the Heart Failure Working Group of the French Society of Cardiology and on behalf French Society of Geriatrics and Gerontology conducted a systematic literature search on the interlink between frailty and HF, met to propose an early frailty screening by non‐geriatricians and to propose ways to implement management plan of frailty. Statements were agreed by expert consensus.ResultsClinically relevant aspects of interlink between frailty and HF have been reported to identify the population eligible for screening and the most suitable screening test(s). The frailty screening program proposed focuses on frailty model defined by an accumulation of deficits including geriatric syndromes, comorbidities, for older patients with HF in different settings of care. The management plan of frailty includes optimization of HF pharmacological treatments and non‐surgical device treatment as well as optimization of a global patient‐centred biopsychosocial blended collaborative care pathway.ConclusionThe current manuscript provides practical recommendations on how to screen and optimize frailty management in older patients with heart failure.