bluuebunny/crossref_metadata_2025_split huggingface dataset:
Haloboration of o‐Alkynyl Phenols Generates Halogenated Bicyclic‐Boronates**
Authors: Yuan Kang , Ingleson Michael J. 
Published: March 2023

AbstractBenzoxaborinines are intermediates en‐route to bicyclic boronates that are important active pharmaceutical ingredients (APIs). Herein, the haloboration of o‐alkynyl‐phenols using BX3 (X=Cl or Br) is disclosed as a route to form C4‐X‐benzoxaborinines with good functional group tolerance. Computational studies indicated that there are two similar in barrier mechanisms: (i) double alkyne haloboration followed by retro‐haloboration; (ii) concerted trans‐haloboration involving an exogenous chloride source. The C4‐halide in these benzoxaborinines is useful, with a one‐pot haloboration‐Negishi cross coupling protocol effective to form benzoxaborinines with an alkyl or an aryl at C4. Therefore this method is a useful addition to the toolbox for synthesising bicyclic‐boronates that are attracting increasing attention as APIs.
N‐(Morpholine‐4‐dithio)phthalimide: A Shelf‐Stable, Bilateral Platform Molecule Enabling Access to Diverse Unsymmetrical Disulfides**
Authors: Asanuma Hayato , Kanemoto Kazuya , Watanabe Tokiharu , Fukuzawa Shin‐ichi 
Published: March 2023

AbstractSynthetic methods for unsymmetrical disulfides are greatly needed owing to their applications in drug discovery, linker chemistry, and materials sciences. In this study, a new shelf‐stable and easy‐to‐prepare bilateral disulfurating platform molecule,N‐(morpholine‐4‐dithio)phthalimide, has been developed for the divergent synthesis of unsymmetrical disulfides. The amino and imide leaving groups of this reagent can be orthogonally transformed. Under acidic conditions, the amino moiety undergoes selective protonation and thus can be displaced by various carbon nucleophiles, such as allyl trimethylsilanes, alkynyl silanes, and electron‐rich arenes, leaving the phthalimide moiety untouched. Meanwhile, the phthalimide leaving group is amenable to substitution under basic or neutral conditions. The combination of these transformations provides rapid access to diverse unsymmetrical disulfides through two C−S bond‐forming reactions.
Pediatric pulmonary valve replacements: Clinical challenges and emerging technologies
Authors: Crago Matthew , Winlaw David S. , Farajikhah Syamak , Dehghani Fariba , Naficy Sina 
Published: March 2023

AbstractCongenital heart diseases (CHDs) frequently impact the right ventricular outflow tract, resulting in a significant incidence of pulmonary valve replacement in the pediatric population. While contemporary pediatric pulmonary valve replacements (PPVRs) allow satisfactory patient survival, their biocompatibility and durability remain suboptimal and repeat operations are commonplace, especially for very young patients. This places enormous physical, financial, and psychological burdens on patients and their parents, highlighting an urgent clinical need for better PPVRs. An important reason for the clinical failure of PPVRs is biofouling, which instigates various adverse biological responses such as thrombosis and infection, promoting research into various antifouling chemistries that may find utility in PPVR materials. Another significant contributor is the inevitability of somatic growth in pediatric patients, causing structural discrepancies between the patient and PPVR, stimulating the development of various growth‐accommodating heart valve prototypes. This review offers an interdisciplinary perspective on these challenges by exploring clinical experiences, physiological understandings, and bioengineering technologies that may contribute to device development. It thus aims to provide an insight into the design requirements of next‐generation PPVRs to advance clinical outcomes and promote patient quality of life.
Combining radiation and the ATR inhibitor berzosertib activates STING signaling and enhances immunotherapy via inhibiting SHP1 function in colorectal cancer
Authors: Liu Chaofan , Wang Xi , Qin Wan , Tu Jingyao , Li Chunya , Zhao Weiheng , Ma Li , Liu Bo , Qiu Hong , Yuan Xianglin 
Published: March 2023

AbstractBackgroundImmune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD‐1) and programmed death‐ligand 1 (PD‐L1) have shown a moderate response in colorectal cancer (CRC) with deficient mismatch repair (dMMR) functions and poor response in patients with proficient MMR (pMMR). pMMR tumors are generally immunogenically “cold”, emphasizing combination strategies to turn the “cold” tumor “hot” to enhance the efficacy of ICIs. ATR inhibitors (ATRi) have been proven to cooperate with radiation to promote antitumor immunity, but it is unclear whether ATRi could facilitate the efficacy of IR and ICI combinations in CRCs. This study aimed to investigate the efficacy of combining ATRi, irradiation (IR), and anti‐PD‐L1 antibodies in CRC mouse models with different microsatellite statuses.MethodsThe efficacy of combining ATRi, IR, and anti‐PD‐L1 antibodies was evaluated in CRC tumors. The tumor microenvironment and transcriptome signatures were investigated under different treatment regimens. The mechanisms were explored via cell viability assay, flow cytometry, immunofluorescence, immunoblotting, co‐immunoprecipitation, and real‐time quantitative PCR in multiple murine and human CRC cell lines.ResultsCombining ATRi berzosertib and IR enhanced CD8+T cell infiltration and enhanced the efficacy of anti‐PD‐L1 therapy in mouse CRC models with different microsatellite statuses. The mechanistic study demonstrated that IR + ATRi could activate both the canonical cGAS‐STING‐pTBK1/pIRF3 axis by increasing cytosolic double‐stranded DNA levels and the non‐canonical STING signaling by attenuating SHP1‐mediated inhibition of the TRAF6‐STING‐p65 axis, via promoting SUMOylation of SHP1 at lysine 127. By boosting the STING signaling, IR + ATRi induced type I interferon‐related gene expression and strong innate immune activation and reinvigorated the cold tumor microenvironment, thus facilitating immunotherapy.ConclusionsThe combination of ATRi and IR could facilitate anti‐PD‐L1 therapy by promoting STING signaling in CRC models with different microsatellite statuses. The new combination strategy raised by our study is worth investigating in the management of CRC.
Cell division cycle‐associated 8 is a prognostic biomarker related to immune invasion in hepatocellular carcinoma
Authors: Wu Haomin , Liu Shiqi , Wu Di , Zhou Haonan , Sui Guoxin , Wu Gang 
Published: March 2023

AbstractBackgroundCell division cycle‐associated 8 (CDCA8) is involved in numerous signaling networks, and it serves a crucial modulatory function in multiple malignant tumors. However, its significance in prognosis and immune infiltration in hepatocellular carcinoma (HCC) remains unclear.Materials and methodsHerein, we examined the CDCA8 levels in tumor tissues, as well as its associated signaling pathways and correlation with immune infiltration. Additionally, we further clarified the prognostic significance of CDCA8 among HCC patients. HCC patient information was recruited from The Cancer Genome Atlas (TCGA). Using bioinformatics, the following parameters were analyzed among HCC patients: CDCA8 expression, enrichment analysis, immune infiltration, and prognosis analysis. Moreover, we employed in vitro investigations, such as, qRT‐PCR, immunohistochemistry (IHC), and cell functional experiments to validate our results.ResultsElevated CDCA8 expression in HCC patients was markedly associated with T stage, pathological status (PS), tumor status (TS), histologic grade (HG), and AFP. Elevated CDCA8 expression HCC patients exhibited reduced overall survival (OS) (p < 0.001), disease‐specific survival (DSS) (p < 0.001), and progress free interval (PFI) H(p < 0.001). According to the ROC analysis, the area under the curve (AUC) was 0.997. Multivariate analysis revealed that CDCA8 was a stand‐alone prognostic indicator of patient OS (p = 0.009) and DSS (p = 0.006). A nomogram was then generated based on the multivariate analysis, and the C‐indexes and calibration chart revealed excellent predictive performance in determining HCC patient outcome. Based on the GSEA analysis, CDCA8 modulated the P53, Notch, PPAR, E2F networks. We observed a direct link between CDCA8 levels and Th2 and T helper cells, and a negative link between CDCA8 levels and dendritic cells (DC), neutrophils, cytotoxic cells, and CD8 T cells. Furthermore, CDCA8 deficiency inhibited liver cancer cell proliferation and invasion.ConclusionIn conclusion, these findings indicate that CDCA8 is a new molecular bioindicator of HCC patient prognosis, and it is an excellent candidate for therapeutic target against HCC.
Network Pharmacology‐Based Approach for Investigating the Role of Xanthii Fructus in Treatment of Allergic Rhinitis
Authors: Liu Xinyue , Yang Yujuan , Li Yumei , Zhang Qiang , Wang Jianwei , Guo Jing , Song Zheying , Liu Zhen , Zhang Yu , Song Xicheng 
Published: March 2023

AbstractXanthii Fructus (XF) has been used for treatment of allergic rhinitis (AR), but its pharmacological mechanism of action remains unclear. We aimed to explore the potential mechanism of XF in treatment of AR by using a network pharmacology approach combined with in vivo verification experiments in this study. We identified 945 AR‐related pathogenic genes, 11 active components in XF and 178 targets of those active components by corresponding databases. Finally, 54 targets of active components from XF in treatment of AR were identified by the Protein‐protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, among which Tumor Necrosis Factor (TNF), Mitogen‐activated Protein Kinase 3 (MAPK3), Prostaglandin G/H Synthase 2 (PTGS2), Epidermal Growth Factor Receptor (EGFR) showed strongest interactions. The molecular docking analysis showed that moupinamide could bind to EGFR at LEU704 and LEU703, and PTGS2 at TRP387; 24‐Ethylcholest‐4‐en‐3‐one was identified to bind to MAPK3 at THR347. The validation of quantitative real‐time reverse transcription PCR (RT‐PCR) showed that XF decreased the levels of MAPK3, PTGS2, and EGFR expression in the nasal mucosa from AR mice gavaged with an XF water decoction. Meanwhile, the levels of interleukin (IL)‐4, IL‐5 and IL‐13were also decreased after the treatment of XF by Enzyme‐linked immunosorbent assay (ELISA). Our results provide the pharmacological mechanism and possible intervention targets of XF in treatment of AR.
Nano‐Biotechnology and Challenges of Drug Delivery System in Cancer Treatment Pathway: Review Article
Authors: Asadipour Erfan , Asgari Mahtab , Mousavi Parastoo , Piri‐Gharaghie Tohid , Ghajari Ghazal , Mirzaie Amir 
Published: March 2023

AbstractIn this review, we discuss Nanotechnology models, which have been developed recently in cancer treatment. Nanotechnology manipulates matter at the atomic and molecular scale to create materials with new and advanced properties. Nano‐biotechnology consists of the branches of nanotechnology that have been applied in biology (molecular and cellular genetics) and biotechnology. Nano‐biotechnology allows us to put components and compounds into cells and build new materials using new methods like assembly. Cancer is a disease caused by an uncontrolled division of abnormal cells in a part of the body. Its therapeutic methods include chemotherapy, radiation, or surgery, but the effects of these techniques are not only on tumor tissue and may affect healthy tissues. Nano‐Biotech applications regarding cancer include drug delivery, treatment, and foresight therapy. This review article aims to obtain a proper mentality of the current technologies of Nano‐biotechnology for cancer treatment.
Type II Polyketide Synthases: A Bioinformatics‐Driven Approach
Authors: Xie Shengling , Zhang Lihan 
Published: March 2023

AbstractBioinformatics has become an indispensable tool for natural products research in the genomic era. One of the key challenges is to accurately convert sequence data of a biosynthetic gene cluster into chemical information such as the enzymatic function or the biosynthetic product structure. Type II polyketide synthase is the most bioinformatically well‐studied class of non‐modular biosynthetic machinery and represents a model system to showcase bioinformatic applications in natural products research. This review takes a bioinformatics‐centered perspective and summarizes the past advances and future opportunities of bioinformatics‐guided research on type II polyketide synthases. How bioinformatics has contributed to deepen the chemical understanding of type II PKSs will be discussed with the focus on enzymology, evolution, structural prediction of the biosynthetic products, genome mining, and the global analyses of their polyketide products.
Popularity bias in personality perspective: An analysis of how personality traits expose individuals to the unfair recommendation
Authors: Yalcin Emre , Bilge Alper 
Published: March 2023

AbstractRecommender systems are subject to well‐known popularity bias issues, that is, they expose frequently rated items more in recommendation lists than less‐rated ones. Such a problem could also have varying effects on users with different gender, age, or rating behavior, which significantly diminishes the users' overall satisfaction with recommendations. In this paper, we approach the problem from the view of user personalities for the first time and discover how users are inclined toward popular items based on their personality traits. More importantly, we analyze the potential unfairness concerns for users with different personalities, which the popularity bias of the recommenders might cause. To this end, we split users into groups of high, moderate, and low clusters in terms of each personality trait in the big‐five factor model and investigate how the popularity bias impacts such groups differently by considering several criteria. The experiments conducted with 10 well‐known algorithms of different kinds have concluded that less‐extroverted people and users avoiding new experiences are exposed to more unfair recommendations regarding popularity, despite being the most significant contributors to the system. However, discrepancies in other qualities of the recommendations for these user characteristics, such as accuracy, diversity, and novelty, vary depending on the utilized algorithm.
Symmetric searchable encryption with supporting search pattern and access pattern protection in multi‐cloud
Authors: Xu Wanshan , Zhang Jianbiao , Yuan Yilin , Wang Xiao 
Published: March 2023

SummarySymmetric searchable encryption (SSE) enables users to search the ciphertext stored on the untrusted cloud without revealing the search keywords, effectively protecting users' privacy. However, most of the existing SSE schemes reveal the search or access pattern during the keyword query, which can be used by the adversary to infer the sensitive information in ciphertext, thus posing a great threat to users' privacy. To address this, we propose an SSE scheme supporting search pattern and access pattern protection in multi‐cloud, called SAPM‐SSE. In our scheme, an index shuffle protocol is proposed to change the content and location of the index after each query, which helps to achieve the protection of search and access pattern. Furthermore, with the purpose of improving the efficiency of shuffling, we construct a shuffling algorithm based on index cache, the number of index entries for shuffling reduced from γ to γ/n (n≥1). Besides, our scheme supports the dynamic update of documents and achieves the forward security in update. Finally, security analysis and experimental results show that our scheme can achieve the protection of search pattern and access pattern with high efficiency.
SCF‐FBXL8 contributes to liver metastasis and stem‐cell‐like features in colorectal cancer cells by mediating ubiquitination and degradation of TP53
Authors: Yao Jing , Wang Xin‐Ping , Yang Jun , Yang Zhe , Zhang Zheng‐Yun 
Published: March 2023

AbstractBackgroundFBXL8 is a conserved F‐box protein, belonging to the ubiquitin ligase complex, which promotes the development and progression of tumours. However, the regulation function and mechanism of FBXL8's involvement in colorectal cancer (CRC) remain unclear.MethodsRT–PCR is used to detect gene expression levels. Protein levels were determined by western blotting and flow cytometry. The bindings of FBXL8 and p53 and ubiquitination levels were detected by cell transfection and immunoprecipitation. The transwell assay was used to measure the ability of cells to migrate and invade. Animal studies were used to verify the function of FBXL8 in vivo.ResultsThe expression of FBXL8 was up‐regulated in CRC tissues, and its overexpression was associated with poor prognosis in CRC patients. The up‐regulation of FBXL8 promoted the proliferation, invasion and migration of CRC tumour cells and maintained the stem‐cell characteristics of colorectal tumour cells. Further analysis demonstrated that FBXL8 targeted p53 and reduced its stability through ubiquitination. Knockout of FBXL8 down‐regulated the proliferation, migration and stem‐like properties of tumour cells. CRC mouse xenograft tumour model confirmed that FBXL8 gene knockout inhibited tumour formation and liver metastasis.ConclusionFBXL8 was highly expressed in CRC. Mechanism studies have shown that FBXL8 degraded tumour suppressor gene p53 by ubiquitination. FBXL8 knockout inhibited the proliferation and stem characteristics of CRC cells, so SCF‐FBXL8‐TP53 has potential to be used as a therapeutic target for CRC in subsequent studies.
Effectiveness of lenvatinib plus immune checkpoint inhibitors in primary advanced hepatocellular carcinoma beyond oligometastasis
Authors: Wang Xiao‐Hui , Liu Chang‐Jun , Wen Hao‐Quan , Duan Xiao‐Hui , Jiao Yu‐Qing , Liu Yu‐Jiang , Chen Min‐Shan , Zhu Kang‐Shun , Mao Xian‐Hai , Zhou Qun‐Fang 
Published: March 2023

AbstractBackgroundTargeted therapy combined with immune checkpoint inhibitors is considered a promising treatment for primary advanced hepatocellular carcinoma (HCC). Nevertheless, the difference between synchronous and asynchronous treatment of lenvatinib with programmed death receptor‐1 (PD‐1) inhibitor in advanced HCC is still unclear. The aim of this investigation is to evaluate the effectiveness of synchronous and asynchronous of lenvatinib and PD‐1 inhibitor on the advanced HCC beyond oligometastasis.MethodsIn this study, 213 patients from four institutions in China were involved. Patients were split into two collections: (1) lenvatinib plus PD‐1 inhibitor were used synchronously (synchronous treatment group); (2) patients in asynchronous treatment group received PD‐1 inhibitor after 3 months of lenvatinib treatment prior to tumour progression. To analyse progression‐free survival (PFS), overall survival (OS), efficacy and safety of patients in both groups, we employed propensity score matching (PSM).ResultsThe 6‐, 12‐ and 24‐month OS rates were 100%, 93.4% and 58.1% in the synchronous treatment group and 100%, 71.5% and 25.3% in the asynchronous treatment group, respectively. In contrast to the asynchronous treatment group, the group treated synchronously exhibited a substantially enhanced OS (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.30–0.66; p < .001). The 6‐, 12‐ and 18‐month PFS rates were 82.6%, 42.6% and 10.8% in the synchronous treatment group and 63.3%, 14.2% and 0% in the asynchronous treatment group, respectively. A significant difference was observed in the PFS rate (HR, 0.46; 95% CI, 0.33–0.63; p < .001) between the two collections.ConclusionsPatients with advanced HCC beyond oligometastasis, simultaneous administration of lenvatinib and PD‐1 inhibitor led to significant improvements in survival.
Difficulties with positive emotion regulation in anorexia nervosa
Authors: Santos Bolade M. , Haynos Ann F. 
Published: March 2023

AbstractIndividuals with anorexia nervosa (AN) have well‐documented difficulties regulating negative emotions, but less is known about positive emotion regulation in this population. To address this gap, we compared responses on the Difficulties in Emotion Regulation Scale‐Positive questionnaire and the traditional DERS questionnaire (measuring negative affect dysregulation) between females with AN (n = 30) and demographically‐matched controls without an eating disorder history (NC; n = 30) and examined relations between positive emotion regulation and clinical symptoms. Results indicated that individuals with AN demonstrated greater difficulty regulating negative (p < 0.001, d = 2.75) and positive (p < 0.001, d = 1.08) emotions compared to NC participants. Specifically, the AN group reported heightened positive emotion nonacceptance (p = 0.004, d = 0.78) and impulsivity (p = 0.003, d = 0.81). Greater positive emotion nonacceptance was associated with higher anxiety (p = 0.015) and depression (p = 0.022) among individuals with AN. Unexpectedly, more positive emotion impulsivity was associated with less restrictive eating in AN (p < 0.001). Findings were largely maintained even after controlling for negative emotion dysregulation and psychotropic medication use. The results suggest that reducing shame related to positive emotions could improve mood in AN; alternatively, relinquishing control when experiencing positive emotion could reduce restriction. More research is warranted on positive emotion regulation as a treatment target for AN.
A flexible copula regression model with Bernoulli and Tweedie margins for estimating the effect of spending on mental health
Authors: Marra Giampiero , Fasiolo Matteo , Radice Rosalba , Winkelmann Rainer 
Published: March 2023

AbstractWe develop a flexible two‐equation copula model to address endogeneity of medical expenditures in a distribution regression for health. The expenditure margin uses the compound gamma distribution, a special case of the Tweedie family of distributions, to account for a spike at zero and a highly skewed continuous part. An efficient estimation algorithm offers flexible choices of copulae and link functions, including logit, probit and cloglog for the health margin. Our empirical application revisits data from the Rand Health Insurance Experiment. In the joint model, using random insurance plan assignment as instrument for spending, a $1000 increase is estimated to reduce the probability of a low post‐program mental health index by 1.9 percentage points. The effect is not statistically significant. Ignoring endogeneity leads to a spurious positive effect estimate.
Introduction to the Special Series “Environmental Monitoring on Global and Local Scales”
Authors: Zotina Tatiana A. , Kudryasheva Nadezhda S. , Soukhovolsky Vladislav G. 
Published: March 2023

Abstract
The ecosystems of Siberia provide valuable services to the human population and afford important climate feedback. However, they are subject to anthropogenic pressures leading to the transformation of ecosystem structure and functions such as deforestation; extraction and transportation of fossil hydrocarbons; mining, refining, and smelting industrial activities; damming of rivers by high-pressure hydroelectric plants, and other activities. The articles in this special series deal with the monitoring of natural ecosystems of Siberia that are located on vast areas of Eurasia, many of which are hard to reach and sparsely populated. The results and approaches of environmental monitoring presented in this special series offer new opportunities for developing the strategy of intelligent management and conservation of vulnerable Siberian ecosystems to meet the challenges of global climate change and unsustainable use of natural resources. Integr Environ Assess Manag 2023;19:970–971. © 2023 SETAC