bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inosine enhances the efficacy of immune‐checkpoint inhibitors in advanced solid tumors: A randomized, controlled, Phase 2 study
Authors: Zhao Haiqing , Zhang Wei , Lu Yuting , Dong Yin , He Zhihao , Zhen Hongchao , Li Qin 
Published: September 2024

AbstractBackgroundThis study aimed to evaluate whether inosine enhances the efficacy of immune‐checkpoint inhibitors in human malignant solid tumors.MethodsThis single‐center, prospective, randomized, open‐label study was conducted, from January 2021 to December 2022, in Beijing Friendship Hospital, Capital Medical University, and participants were randomly assigned (1:1) to either the inosine (trial) or non‐inosine (control) group that received inosine (dosage: 0.2 g, three times/day) + PD‐1/PD‐L1 inhibitor or only PD‐1/PD‐L1 inhibitor ± targeted ± chemotherapy, respectively. Efficacy was assessed every 6 weeks (i.e., after every two–three treatment cycles). The primary endpoint was the objective response rate (ORR); the secondary endpoints were disease control rate, overall survival (OS), and progression‐free survival (PFS). The trial was registered at ClinicalTrials.gov (NCT05809336).ResultsAmong the 172 participants with advanced malignant solid tumors, 86 each were assigned to the inosine and non‐inosine groups, wherein the median PFS (95% CI) was 7.00 (5.31–8.69) and 4.40 (3.10–5.70) months, respectively (hazard ratio [HR] 0.63; 95% CI 0.44–0.90, p = 0.011), and the ORR was 26.7% and 15.1%, respectively (p = 0.061). In the inosine and non‐inosine groups, the median OS was not reached and was 29.67 (95% CI 17.40–41.94) months, respectively (HR 1.05 [95% CI 0.59–1.84], p = 0.874). Compared with the non‐inosine group, the median PFS and ORR of the inosine group were significantly prolonged and improved in the multiple exploratory subgroup analyses. The safety analysis showed that Grades 3 and 4 adverse reactions occurred in 25 (29%) and 31 (36%) patients in the inosine and non‐inosine groups, respectively, and tended to decrease in the inosine group compared with the non‐inosine group.ConclusionInosine had a tendency to enhance the efficacy of immune‐checkpoint inhibitors and reduced immunotherapy‐related adverse reactions.
The COVID‐19 pandemic and associated declines in cancer incidence by race/ethnicity and census‐tract level SES, rurality, and persistent poverty status
Authors: Liu Benmei , Yu Mandi , Byrne Jeffrey , Cronin Katheen A. , Feuer Eric J. 
Published: September 2024

AbstractBackgroundThe COVID‐19 pandemic had a significant impact on cancer screening and treatment, particularly in 2020. However, no single study has comprehensively analyzed its effects on cancer incidence and disparities among groups such as race/ethnicity, socioeconomic status (SES), persistent poverty (PP), and rurality.MethodsUtilizing the recent data from the United States National Cancer Institute's Surveillance, Epidemiology, and End Results Program, we calculated delay‐ and age‐adjusted incidence rates for 13 cancer sites in 2020 and 2015–2019. Percent changes (PCs) of rates in 2020 compared to 2015–2019 were measured and compared across race/ethnic, census tract‐level SES, PP, and rurality groups.ResultsOverall, incidence rates decreased from 2015–2019 to 2020, with varying PCs by cancer sites and population groups. Notably, NH Blacks showed significantly larger PCs than NH Whites in female lung, prostate, and colon cancers (e.g., prostate cancer: NH Blacks −7.3, 95% CI: [−9.0, −5.5]; NH Whites: −3.1, 95% CI: [−3.9, −2.2]). Significantly larger PCs were observed for the lowest versus highest SES groups (prostate cancer), PP versus non‐PP groups (prostate and female breast cancer), and all urban versus rural areas (prostate, female breast, female and male lung, colon, cervix, melanoma, liver, bladder, and kidney cancer).ConclusionsThe COVID‐19 pandemic coincided with reduction in incidence rates in the U.S. in 2020 and was associated with worsening disparities among groups, including race/ethnicity, SES, rurality, and PP groups, across most cancer sites. Further investigation is needed to understand the specific effects of COVID‐19 on different population groups of interest.
Global disparities in cancer supportive care: An international survey
Authors: Chan Alexandre , Eng Lawson , Jiang Changchuan , Dagsi Mary , Ke Yu , Tanay Mary , Bergerot Cristiane , Dixit Niharika , Gutiérrez Ana Cardeña , Velazquez Ana I. , Islami Farhad , Soto‐Perez‐de‐Celis Enrique 
Published: September 2024

AbstractBackgroundThe global cancer burden is rising, particularly in low‐ and middle‐income countries (LMIC), highlighting a critical research gap in understanding disparities in supportive care access. To address this, the Multinational Association of Supportive Care in Cancer (MASCC) Health Disparities Committee initiated a global survey to investigate and delineate these disparities. This study aims to explore and compare supportive care access disparities between LMIC and High‐Income Countries (HIC).MethodsAn online cross‐sectional survey was conducted among active members of MASCC. Members, representing diverse healthcare professions received email invitations. The survey, available for 3 weeks, comprised sections covering (1) sociodemographic information; (2) clinical service/practice‐related disparities in their region/nation; (3) population groups facing disparities within their region or country. Chi‐squared or Fisher's exact test for cross‐sectional analyses, and a multivariable logistic regression model was employed for statistical analysis.ResultsA total of 218 active members participated, with one‐quarter (26.6%) from LMIC and 18.4% ethnic minorities, timely cancer care (43.7%) and timely supportive care (45.0%) emerged as the most pressing disparities globally. Notably, participants from LMIC underscored cancer drug affordability (56.4%) and supportive care guideline implementation (56.4%) as critical issues. Economically disadvantaged populations were noted as more likely to face disparities by both LMIC and HIC (non‐US‐based) respondents, while US‐based respondents identified racial/ethnic minorities as facing more disparities.ConclusionThis global survey reveals significant disparities in cancer supportive care between LMIC and HIC, with a particular emphasis on medication affordability and guideline implementation in LMIC. Addressing these disparities requires targeted intervention, considering specific regional priorities.
Phenolic Profiling, In Vitro Antiglycation, Antioxidant Activities, and Antidiabetic Effect of Algerian Trigonella Foenum‐Graecum L. in Rats Administered a β‐Cell Toxicant
Authors: Hachouf Maram , Aouacheri Ouassila , Saka Saad , Marzocchi Adua , Carlo Tenore Gian 
Published: September 2024

AbstractThis study sought to quantitatively assess individual and total polyphenols, mineral composition, antioxidant and antiglycation activities of Algerian fenugreek seeds (AFS) as well as the antidiabetic effect of its supplementation on streptozotocin‐induced diabetic rats. Forty rats were divided into four groups (i) non diabetic rats, (ii) non diabetic rats +10 % AFS, (iii) diabetic rats, (iv) diabetic rats +10 % AFS. Flame‐SAA analysis revealed a rich content in micro‐elements, HPLC DAD‐FLD analysis revealed twenty components with rutin and ferulic acid being the major compounds in AFS hydro‐methanolic extract while spectrophotometric assays scrutinized moderate contents in total phenolics and flavonoids. The extract was potent in scavenging ABTS⋅+ and DPPH+ (42.06±2.14 and 55.84±4.14 mg TE/g), reducing Fe3+ and Mo6+ (35.12±2.45 and 29.89±3.12 mg TE/g) and inhibiting AGEs (IC50=1.03±0.02 mg/ml). In vivo, 10 %AFS‐ supplemented diet (w/w) was found to elicit a significant reduction in glycemia (66.74 %), TNF α (9.4 %), IL‐6 (23.74 %), CRP (31.10 %), liver enzymes, lipid peroxidation (MDA) (47.24 %;30 %), protein carbonyl (PCO) (28.35 %; 27.15 %), improvement in insulin level (79.74 %), reduced glutathione amount (GSH) (41.01 %; 16.55 %), glutathione peroxidase (GPx) (45.80 %; 56.37 %), catalase (CAT) (24.44 %; 35.42 %) and glutathione‐S‐transferase (GST) (22.78 %; 22.90 %) activities, in liver and pancreas respectively, along with a rejuvenation of hepatic and pancreatic histological features. These outcomes disclosed that AFS is endowed with biologically effective components which could be decent applicant to attain the objective of mitigating glycation, oxidative stress and diabetes‐related complications.
Phosphoinositide 3‐Kinase Inhibitors from Gladiolus Segetum Ker‐Gawl Corms Supported by Network Pharmacology
Authors: Khalaf Mahmoud Basma , Abdelwahab Miada F. , Alzahraa Mokhtar Fatma , Sayed Ahmed M. , Zhang Jianye , Alsenani Faisal , Elsherief Hany A. M. , Altemani Faisal H. , Algehainy Naseh A. , Lehmann Leane , Ramadan Abdelmohsen Usama , Abd El‐Kader Adel M. 
Published: September 2024

AbstractGladiolus segetum Ker‐Gawl corms total extract exhibited remarkable in vitro anti‐proliferative effects against panel of cancer cell lines; including human colon carcinoma (Caco‐2), human breast cancer (MCF7) and hepatocellular carcinoma (HepG2) cell lines with IC50 values of 7.4, 9.1 and 11.2 μg/ml, respectively. The total ethanolic extract of G. segetum Ker‐Gawl corms was subjected to untargeted metabolomics profiling using LC‐HR‐ESI‐MS, which revealed the presence of various clusters of phytoconstituents as triterpenes, anthraquinones, flavonoids and phenolic derivatives. Network pharmacology study was performed for all identified compounds, the formed networks identified 73 intersected genes. The diagrammatic illustration of the top pathways revealed that phosphoinositide 3‐kinase (PI3 K) gene is the effective dominant gene in the top four KEGG pathways. Upon molecular docking and molecular dynamics investigation, kaempferol‐3‐O‐glucopyranoside was suggested to be key anticancer metabolite. Interestingly, cytotoxic investigation of this compound revealed potential activity against the tested cancer cell lines (Caco‐2, MCF7 and HepG2) with IC50 values of 6.2, 8.5 and 9.3 μg/ml, respectively. The present study highlighted the potential of G. segetum Ker‐Gawl as a promising source of interesting anticancer scaffolds.
Research Progress on the Role of Cartilage Endplate in Intervertebral Disc Degeneration
Authors: Ma Zhong , Liu Xin , Zhang Mingtao , Wu Zuolong , Zhang Xianxu , Li Shicheng , An Jiangdong , Luo Zhiqiang 
Published: September 2024

ABSTRACTLow back pain significantly impacts individuals' quality of life, with intervertebral disc degeneration (IDD) being a primary contributor to this condition. Currently, IDD treatment primarily focuses on symptom management and does not achieve a definitive cure. The cartilage endplate (CEP), a crucial nutrient‐supplying tissue of the intervertebral disc, plays a pivotal role in disc degeneration. This review examines the mechanisms underlying CEP degeneration, summarizing recent advancements in understanding the structure and function of CEP, the involvement of various signaling pathways, and the roles of cartilage endplate stem cells (CESCs) and exosomes (Exos) in this process. The aim of this review is to provide a comprehensive reference for future research on CEP. Despite progress in understanding the role of CEP in IDD, the mechanisms underlying CEP degeneration remain incompletely elucidated. Future research poses significant challenges, necessitating further investigations to elucidate the complexities of CEP.
The Multifunctional Preprotein Binding Domain of SecA
Authors: Giotas Emmanouil , Aikaterini Kaplani Stavroula , Eleftheriadis Nikolaos 
Published: September 2024

AbstractSec‐pathway is the main protein secretion pathway in prokaryotes and is essential for their survival. The motor protein SecA is the main coordinator of the pathway in bacteria as it is has evolved to perform multiple tasks, acting like a “swiss army knife”, from binding pre‐proteins to altering its oligomeric and conformational states. This study focuses on the role of its Preprotein Binding Domain (PBD), which is a key protein module that identified in three conformational states (Wide‐Open (WO), Open (O) and Closed (C)). A thorough analysis was conducted to identify PBD's inter‐ and intra‐protomeric interactions, highlighting the most significant and conserved ones. Both crystallographic and biophysical data indicate that the WO state is the main during dimerization, while the monomeric structure can adopt all three states. C‐tail, StemPBD and 3β‐tipPBD are important elements for the stabilization of different oligomeric and conformational states, as they offer specific interactions. Alterations in the lipophilicity of the StemPBD causes increased proteins dynamics or/and Prl phenotype. In the C state, 3β‐tipPBD interacts and opens the ATPase motor. We hypothesize that this partial opening of the motor with the increased dynamics describes the Prl phenotype.
Circular Polyesters Based on Lactones
Authors: Dong Run‐Hua , Guo Jia‐Yin , Sun Hang‐Ming , Xu Tie‐Qi 
Published: September 2024

AbstractThe development of modern society is closely related to polymer materials. As a typical example, plastic is an indispensable material in modern society. However, despite their low cost and widespread use, most discarded polymers are not recyclable, and their widespread use leads to the depletion of natural resources. In addition, the accumulation of polymer materials and their evolution in the environment can also cause serious environmental problems. Although the polymers can be reused by physical recovery, the properties of the polymers produced by this process are significantly reduced. Chemical recycling to original monomers for repolymerization offers a promising closed‐loop method to transition from a linear plastic economy toward a more sustainable circular model. This review focuses on recent developments and outlines future challenges of emerging chemically recyclable polyesters.
Construction of Cyclodextrin‐Based Covalent Organic Frameworks for Efficient Encapsulation of Menthol
Authors: Tong Yuxing , Liu Ben , Yu Yang , Wang Yixin , Yan Qunshan , Huang Dekang , Zhu Yanqiu , Xiang Yonggang 
Published: September 2024

AbstractThe application of flavoring ingredients like menthol in the food industry is hindered by their high volatility and poor thermal stability, which lead to significant losses during processing and storage. Encapsulation of flavors into porous materials to obtain inclusion complexes (ICs) has proved to be an efficient strategy. In the present study, we synthesized a series of relatively food‐safe three‐dimensional anionic cyclodextrin‐based covalent organic frameworks (CD‐COFs) with spiroborate linkages using a facile microwave‐assisted method. The high surface area and newly formed cavities of COFs significantly enhanced the encapsulation efficiency of menthol compared to native CD materials. Our findings revealed that γ‐CD‐COF−Li, with Li+ as the counterion, achieved superior encapsulation efficiency of 25.9 %, outperforming γ‐CD‐COF−Na, γ‐CD‐COF−K and α‐CD‐COF−Li under the same conditions. Thermal stability measurements show that the menthol/γ‐CD‐COF−Li‐ICs effectively stabilize menthol against heat evaporation at elevated temperatures due to the strengthened interaction between menthol and γ‐CD‐COF−Li. The promising results of this research suggest that rapid advancements in COF technology will provide new opportunities for enhancing the stability of flavoring ingredients in the food industry.
Copper‐Surface‐Mediated Synthesis of sp2 Carbon‐Conjugated Covalent Organic Framework Photocathodes for Photoelectrochemical Hydrogen Evolution
Authors: Lu Yang , Li Wenyan , Sun Chenyu , Tang Yawen , Cheng Lei , Sun Hanjun 
Published: September 2024

AbstractSp2‐carbon (sp2‐c) covalent organic frameworks (COFs), featuring distinctive π‐conjugated network structures, facilitate the migration of photo‐generated carriers, rendering them exceptionally appealing for applications in photoelectrochemical water splitting. However, owing to the powdery nature of COFs, leaving anchor the sp2‐c COFs powder tightly onto a conductive substrate challenging. Here, we propose a method for preparing photoactive substance‐conductive substrate integrated photocathodes through copper surface‐mediated knoevenagel polycondensation (Cu‐SMKP), this approach results in a uniform and stable sp2‐c COF film, directly grown on commercial copper foam (COFTh‐Cu). The COFTh‐Cu demonstrates a high H2‐evolution photocurrent density of 56 μA cm−2 at 0.3 V vs. RHE, sustaining stability for 12 h. The as‐prepared COFTh‐Cu represents a 4.5‐fold increase in current density compared to traditional spin‐coating methods and outperforms most COF photocathodes without cocatalysts. This innovative copper surface‐mediated approach for preparing photocathodes opens up a crucial pathway towards the realization of highly active COF photocathodes.
Catalytic Performance of Chiral Tetraaza‐Bridged Calix[4]arene[2]triazine Derivatives for Enantioselective Michael Reactions
Authors: Ozgun Ummu , Genc Hayriye Nevin 
Published: September 2024

ABSTRACTNovel chiral tetraaza‐bridged calix[4]arene[2]triazine‐based organocatalysts were synthesized and used for catalytic asymmetric Michael reaction of acetylacetone to various aromatic nitrostyrenes. Chiral subunits (R)‐ and (S)‐1,2,3,4‐tetrahydro‐1‐naphthylamine were attached to the tetraaza‐bridged calix[4]arene[2]triazine platform in both enantiomeric forms. The R configuration of the major enantiomer of the Michael product was obtained when 3a was used as catalyst, and the S configuration was obtained when 3b was used as catalyst. This indicated that the configuration of the Michael product was controlled by the chiral calixarene moiety. The Michael adducts were obtained in excellent yields (91%) and enantioselectivities (98%).
Anticoagulant Impact on Clinical Outcomes of Pulmonary Embolism Compared With Thrombolytic Therapy; Meta‐Analysis
Authors: Su Yang , Zou Dongmei , Liu Yi , Wen Chaoqun , Zhang Xialing 
Published: September 2024

ABSTRACTBackgroundPulmonary embolism (PE) is a critical condition requiring effective management strategies. Several options are available, including thrombolytic therapy and anticoagulants.ObjectivesTo assess the impact of thrombolytic therapy either combined with anticoagulant (AC) or alone versus AC alone on mortality, recurrence, clinical deterioration, bleeding, and hospital stay.MethodThis study included 25 previously published studies from 1990 to 2023, with a total of 12 836 participants. Dichotomous and continuous analysis models were used to evaluate outcomes, with heterogeneity and publication bias tests applied. A random model was used for data analysis. Several databases were searched for the identification and inclusion of studies, such as Ovid, PubMed, Cochrane Library, Google Scholar, and Embase.ResultsFor sub‐massive PE, CDT plus AC significantly reduced in‐hospital, 30‐day, and 12‐month mortality compared to AC alone, odds ratio (OR) of −0.99 (95% CI [−1.32 to −0.66]), with increased major bleeding risk but no difference in minor bleeding or hospital stay, OR = 0.46, 95% CI [−0.03 to 0.96]). For acute intermediate PE, systemic thrombolytic therapy did not affect all‐cause or in‐hospital mortality but increased minor bleeding, reduced recurrent PE, and prevented clinical deterioration. The heterogeneity of different models in the current study varied from 0% to 37.9%.ConclusionThe addition of CDT to AC improves mortality outcomes for sub‐massive PE but raises the risk of major bleeding. Systemic thrombolytic therapy reduces recurrence and clinical decline in acute intermediate PE despite increasing minor bleeding. Individualized patient assessment is essential for optimizing PE management strategies.
Discovery of ICOS‐Targeted Small Molecules Using Affinity Selection Mass Spectrometry Screening
Authors: Zhang Longfei , Calvo‐Barreiro Laura , de Sousa Batista Victor , Świderek Katarzyna , Gabr Moustafa T. 
Published: September 2024

AbstractInducible T cell co‐stimulator (ICOS) is a positive immune checkpoint receptor expressed on the surface of activated T cells, which could promote cell function after being stimulated with ICOS ligand (ICOS−L). Although clinical benefits have been reported in the ICOS modulation‐based treatment for cancer and autoimmune disease, current modulators are restricted in biologics, whereas ICOS‐targeted small molecules are lacking. To fill this gap, we performed an affinity selection mass spectrometry (ASMS) screening for ICOS binding using a library of 15,600 molecules. To the best of our knowledge, this is the first study that utilizes ASMS screening to discover small molecules targeting immune checkpoints. Compound 9 with a promising ICOS/ICOS−L inhibitory profile (IC50=29.38±3.41 μM) was selected as the template for the modification. Following preliminary structure‐activity relationship (SAR) study and molecular dynamic (MD) simulation revealed the critical role of the ortho‐hydroxy group on compound 9 in the ICOS binding, as it could stabilize the interaction via the hydrogen bond formation with residuals on the glycan, and the depletion could lead to an activity lost. This work validates a promising inhibitor for the ICOS/ICOS−L interaction, and we anticipate future modifications could provide more potent modulators for this interaction.
Federated learning based multi‐head attention framework for medical image classification
Authors: Firdaus Naima , Raza Zahid 
Published: September 2024

AbstractIn this study, we propose a novel Federated Learning Based Multi‐Head Attention (FBMA) framework for image classification problems considering the Independent and Identically Distributed (IID) and Non‐Independent and Identically Distributed (Non‐IID) medical data. The FBMA architecture integrates FL principles with the Multi‐Head Attention mechanism, optimizing the model performance and ensuring privacy. Using Multi‐Head Attention, the FBMA framework allows the model to selectively focus on important regions of the image for feature extraction, and using FL, FBMA leverages decentralized medical institutions to facilitate collaborative model training while maintaining data privacy. Through rigorous experimentation on medical image datasets: MedMNIST Dataset, MedicalMNIST Dataset, and LC25000 Dataset, each partitioned into Non‐IID data distribution, the proposed FBMA framework exhibits high‐performance metrics. The results highlight the efficacy of our proposed FBMA framework, indicating its potential for real‐world applications where image classification demands both high accuracy and data privacy.
Bridge‐Dependent Donor‐Metal‐Acceptor‐Metal‐Donor (D–M–A–M–D) Systems: From Charge Transfer to Electron Transfer in Dioxolene‐Ge‐Diimine Complexes
Authors: Arsenyeva Kseniya V. , Klimashevskaya Anastasiya V. , Maleeva Arina V. , Arsenyev Maxim V. , Chegerev Maxim G. , Starikova Alyona A. , Yakushev Ilya A. , Cherkasov Anton V. , Piskunov Alexandr V. 
Published: September 2024

AbstractSynthesis and structural characterization of a family of germanium‐dioxolene complexes with ditopic N‐donor ligands (L1‐L5) (L1=1,2‐bis(pyridin‐2‐ylmethylene)hydrazine L2=1,6‐bis‐(pyridin‐2‐yl)‐2,5‐diaza‐1,5‐hexadiene, L3=N,N‐bis(pyridin‐2‐ylmethylene)‐1,4‐benzenediamine, L4=N,N‐bis(pyridin‐2‐ylmethylene)‐(biphenyl)‐4,4‐diamine, L5=2,2’‐azopyridine) is reported. The reaction of germanium bis‐catecholate with bridging ligands L1 – L4, differing by the nature of the linker between pyridine sites gives rise to dinuclear digermanium complexes (36Cat2Ge)2L1−4 (36Cat=dianion of 3,6‐di‐tert‐butylcatechol) 1–4 of DMAMD type (donor‐metal‐acceptor‐metal‐donor) with a charge transfer in the UV‐Vis region. In opposite, the interaction of the 36Cat2Ge with 2,2’‐azopyridine (L5) results in the two‐electron transfer from the donor 36Cat2− ligands to the azopyridine bridge forming stable open‐shell complex 5 [(36SQ)(36CatGe)]2(L5)2− (36SQ=radical‐anionic semiquinonate ligand). Molecular structures of compounds 3 and 5 were determined by single crystal X‐ray diffraction analysis. Electronic structures of complexes 1–5 were studied by means of DFT calculations.