bluuebunny/crossref_metadata_2025 huggingface dataset:
Blue LED light‐promoted CuCl2‐catalyzed three component reaction of styrenes, indoles, and diselenides
Authors: Yin Xianjie , Wang Helin , Shen Lei , Zeng Qingle
Published: August 2023

A three‐component reaction of olefins, indoles, and diaryl diselenides catalyzed by copper chloride under irradiation of blue LED light is disclosed. Various diaryl diselenides including diheteroaryl diselenides are suitable for this bifunctionalization of olefins. This protocol provides 26 examples of β‐(hetero)arylselenyl indoles in 60%–87% yields. The proposed mechanism involves activation of diaryl diselenides by coordination with copper chloride, generation of arylselenium cations by heterolysis of activated diaryl diselenides, electrophilic addition of arylselenium cations to styrenes, and then Friedel–Crafts‐type alkylation at the 3‐position of NH‐indoles.
Anthracene appended organotin (IV) compounds: Synthesis, structure elucidation and their cytotoxicity against A549 and RBL cancer cell lines
Authors: Paul Anup , Khan Rais Ahmad , Shaik Gouse M. , Shaik Jilani P. , Rai Avdhesh K. , Guedes da Silva M. Fátima C. , Pombeiro Armando J. L.
Published: August 2023

Two new anthracene Schiff base triorganotin (IV) compounds trimethylstannyl(E)‐4‐((anthracen‐9‐ylmethylene)amino)benzoate (1) and triphenylstannyl(E)‐4‐((anthracen‐9‐ylmethylene)amino)benzoate (2) were synthesized by mixing trimethylstannyl (or triphenylstannyl) 4‐aminobenzoate and 9‐anthraldehyde in anhydrous toluene under refluxing conditions. Elemental analysis, FT‐IR, 1H‐NMR, 119Sn NMR and ESI‐MS were used to determine the composition of the compounds. X‐ray diffraction analyses revealed the structural details of the compounds. The in vitro cytotoxicity assessment of these compunds was screened against human A‐549 (lung carcinoma) and rat RBL (leukemia) cancer cell lines. Both compounds displayed a pronounced in vitro cytotoxic effect on the subjected cancer cell lines. Notably, the proliferation of A‐549 cells experienced substantial inhibition in the presence of compound 2. The mode of interaction with Hsp90 and NF‐κB p65 proteins responsible for cancer propagation was also assessed by molecular docking. Compounds 1 and 2 bind to the Hsp90 protein with binding energies of −307.65 and −373.45 kcal/mol, respectively, while to NF‐κB p65 protein the binding energies are of −329.35 and −395.35 kcal/mol, in the same order. Compound 2 exhibited a significantly high binding affinity to NF‐κB p65 and Hsp90 proteins validating our experimental findings from the in vitro experiments.
Anisotropy induced in magnetic field in GNPs/epoxy composites used as an effective heat dissipation electronic packaging material
Authors: Yan Zhengyang , Zhang Xiaohui , Gao Yu , Kong Zisong , Ma Xiaolong , Gou Quan , Liang Huiming , Cai Xiaoming , Tan Honglin , Cai Jinming
Published: August 2023

This article investigates the effect of different magnetic fields on modulating the alignment of graphene nanoplatelets (GNPs) and their impact on the thermal conductivity of epoxy nanocomposites. Various nanocomposite specimens were fabricated with different GNP contents by using magnetically field‐aligned GNPs in the fabrication process to enhance the thermal conductivity. The results showed that the in‐plane thermal conductivity of the Bmf (Bidirectional magnetic field) sample with 5 wt% GNPs added reached 0.75 W m−1 K−1, which is 276.6% higher than that of pure epoxy resin and the anisotropy coefficient (K∥/K⊥) reached 3.3. In addition, temperature rise tests were performed to simulate the thermal conductivity of nanocomposites used as an electronic packaging material, and the results indicated that the composites achieved a significant increase in in‐plane thermal conductivity with a lower amount of filler. This provides valuable insights into the preparation of thermally conductive composites and demonstrates their potential as a thermal management packaging material for next‐generation electronic devices.
Capacitors based on PEDOT nanowire electrodeposits
Authors: Gacitúa Manuel Alejandro , del Valle María Angelica , Ramírez Andrés Mauricio
Published: August 2023

The capacitive properties of poly(3,4‐ethylenedioxythiophene) nanowires (PEDOT‐nw) obtained in situ by the electrosynthesis of EDOT in acetonitrile by cyclic voltammetry on a transparent ITO electrode that has been previously modified with a thin layer of PEDOT, on which mesoporous SiO2 is deposited. Silica acts as a template for the generation of polymer nanowires. The voltammetric profiles are consistent with a large increase in the surface area of the electrode, while their Raman spectroscopy and SEM microscopy demonstrate the formation of polymer nanostructures on the electrode surface. Also, by SEM, the presence of PEDOT deposit is verified in the form of nanowires 30 nm in diameter. On the other hand, galvanostatic measurements show a 20 times higher specific capacity for PEDOT‐nw (516.12 Fg−1) compared to PEDOT bulk (19.62 Fg−1). In the case of PEDOT‐nw, it is also worth noting a 92.3% retention capacity after 1000 successive charge/discharge cycles. Thus, it is verified that PEDOT‐nw modified electrodes are an excellent candidate to be used in polymer‐based capacitors.
Curing reactions of liquid hydridopolycarbosilanes with vinyl or allyl groups
Authors: Qian Binjie , Cao Biwen , Chu Mingyu , Li Yubing , Ma Hanyu , Guo Rongye , Wan Liqiang
Published: August 2023

Liquid hydridopolycarbosilanes (LHPCS) with vinyl or allyl groups have attracted significant research interest due to their low curing temperature and high ceramic yield. In this study, allyl‐terminated hydridopolycarbosilane (AHPCS) and vinyl‐terminated hydridopolycarbosilane (VHPCS) were prepared by the Grignard coupling reaction and characterized by NMR and Fourier infrared spectroscopy (FTIR). And the curing reactions of AHPCS and VHPCS with or without initiators (dicumyl peroxide [DCP], tert‐Butyl peroxybenzoate [TBPB]) or Karstedt catalyst were investigated using differential scanning calorimetry and in‐situ FTIR. The main curing reactions of VHPCS and AHPCS are the double bond free radical polymerization and hydrosilylation reaction, respectively. The addition of initiators and Karstedt catalyst could promote the corresponding curing reaction and increase the weight residual at 1000°C. The thermal properties of the cured resins were investigated by thermogravimetric analysis. The addition of initiators and catalyst could significantly increase the weight residual of VHPCS and AHPCS, respectively. The addition of the Karstedt catalyst increased the weight residual of AHPCS from 75.6% to 83.1%. In addition, the addition of TBPB and DCP increased the weight residual of VHPCS from 74.2% to 81.2% and 80.2%, respectively.
Advances in Organic Thermoelectric Devices for Multiple Applications
Authors: Ma Yingqiao , Di Chong‐an , Zhu Daoben
Published: August 2023

Organic thermoelectric (OTE) devices composed of π‐conjugated molecules are the basic building blocks for self‐powered integrated organic electronics. In addition to molecular design and doping strategies, the highly tunable energy conversion process in OTE devices has drawn significant research interest. Specifically, the diverse physical properties of organic semiconductors, novel device geometry design, and advanced fabrication techniques combined enable the OTE device to be a powerful multiscale platform from single‐molecular scale to thin films for modulating the TE performance, studying the fundamental charge transport mechanism, exploring novel energy conversion phenomenon, and realizing various functionalities. Here, the authors comprehensively review the recent experimental and theoretical advances in related topics of OTE devices, including multifunctional, external physical fields, and temperature modulated, as well as quantum OTE devices. The remaining issues and perspectives toward future OTE device research are also discussed at the end.
The clock gene Cryptochrome 1 is involved in the photoresponse of embryonic hatching behavior in Bombyx mori
Authors: Yuan Xiao‐Nan , Luo Cheng , Zhao Qi‐Fan , Zhong Si‐Yin , Hang Qi , Dai Tai‐Ming , Pan Zhong‐Hua , Sima Yang‐Hu , Qiu Jian‐Feng , Xu Shi‐Qing
Published: August 2023

The hatching of insect eggs is a classic circadian behavior rhythm controlled by the biological clock. Its function is considered to impose a daily rhythm on the embryo, allowing it to hatch within a permissible time window. However, the molecular pathways through which the clock affects embryonic hatching behavior remain unclear. Here, we utilized a clock gene Cryptochrome1 (Cry1) knockout mutant to dissect the pathways by which the circadian clock affects embryonic hatching rhythm in the silkworm. In the Cry1 mutant, the embryo hatching rhythm was disrupted. Under the constant light or constant dark incubation conditions, mutant embryos lost their hatching rhythm, while wild‐type embryos hatch exhibiting free‐running rhythm. In the light‐dark cycle (LD), the hatching rhythm of CRY1‐deficient silkworms could not be entrained by the LD photoperiod during the incubation period. The messenger RNA levels and enzymatic activities of Cht and Hel in the mutant embryos were significantly reduced at circadian time 24 (CT24). Transcriptome analysis revealed significant differences in gene expression at CT24 between the Cry1 knockout mutant and the wild‐type, with 2616 differentially expressed genes identified. The enriched Gene Ontology pathway includes enzyme activity, energy availability, and protein translation. Short neuropeptide F signaling was reduced in the CT24 embryonic brain of the mutant, the expression of the neuropeptide PTTH was also reduced and the rhythm was lost, which further affects ecdysteroid signaling. Our results suggested that the silkworm circadian clock affects neuropeptide‐hormone signaling as well as physiological functions related to hatching, which may regulate the hatching rhythm.
Repurposing of investigational cancer drugs: Early phase discovery of dengue virus NS2B/NS3 protease inhibitors
Authors: Saleem Hafiza N. , Kousar Summara , Jiskani Ammar Hassan , Sohail Iqra , Faisal Amir , Saeed Muhammad
Published: August 2023

Dengue fever is a neglected vector‐borne disease and is more prevalent in Asia. Currently, no specific treatment is available. Given the time and cost of de novo drug discovery and development, an alternative option of drug repurposing is becoming an effective tool. We screened a library of 1127 pharmacologically active, metabolically stable, and structurally diverse small anticancer molecules to identify inhibitors of the dengue virus (DENV) NS2B/NS3 protease. Enzyme kinetics and inhibition data revealed four B‐cell lymphoma 2 inhibitors, that is, ABT263, ABT737, AT101, and TW37, as potent inhibitors of DENV NS2B/NS3 protease, with IC50 values of 0.86, 1.15, 0.81, and 0.89 µM, respectively. Mode of inhibition experiments and computational docking analyses indicated that ABT263 and ABT737 are competitive inhibitors, whereas AT101 and TW37 are noncompetitive inhibitors of the protease. With further evaluation, the identified inhibitors of the DENV NS2B/NS3 protease have the potential to be developed into specific anti‐dengue therapeutics.
Role and Therapeutic Potential for Targeting Fibroblast Growth Factor 10/FGFR1 in Relapsed Rheumatoid Arthritis
Authors: Meng Xiaohui , Chen Zechuan , Li Teng , Nie Zhixing , Han Haihui , Zhong Sheng , Yin Zhinan , Sun Songtao , Xie Jun , Shen Jun , Xu Xirui , Gao Chenxin , Ran Lei , Xu Bo , Xiang Zheng , Wang Jianye , Sun Pengfei , Xin Pengfei , A Xinyu , Zhang Chengbo , Qiu Guowei , Gao Huali , Bian Yanqin , Xu Minglan , Cao Boran , Li Fang , Zheng Lin , Zhang Xiaoming , Xiao Lianbo
Published: August 2023

Objective

Fibroblast‐like synoviocytes (FLSs) contribute to inflammation and joint damage in rheumatoid arthritis (RA). However, the regulatory mechanisms of FLSs in relapse and remission of RA remain unknown. Identifying FLS heterogeneity and their underlying pathogenic roles may lead to discovering novel disease‐modifying antirheumatic drugs.

Methods

Combining single‐cell RNA sequencing (scRNA‐seq) and spatial transcriptomics, we sequenced six matched synovial tissue samples from three patients with relapse RA and three patients in remission. We analyzed the differences in the transcriptomes of the FLS subsets between the relapse and remitted phases. We validated several key signaling pathways using quantitative real‐time PCR (qPCR) and multiplex immunohistochemistry (mIHC). We further targeted the critical signals in vitro and in vivo using the collagen‐induced arthritis (CIA) model in rats.

Results

Lining and sublining FLS subsets were identified using scRNA‐seq. Differential analyses indicated that the fibroblast growth factor (FGF) pathway was highly activated in the lining FLSs from patients with relapse RA for which mIHC confirmed the increased expression of FGF10. Although the type I interferon pathway was also activated in the lining FLSs, in vitro stimulation experiment suggested that it was independent of the FGF10 pathway. FGF10 knockdown by small interfering RNA in FLSs significantly reduced the expression of receptor activator of NF‐κB ligand. Moreover, recombinant FGF10 protein enhanced bone erosion in the primary human‐derived pannus cell culture, whereas the FGF receptor (FGFR) 1 inhibitor attenuated this process. Finally, administering an FGFR1 inhibitor displayed a therapeutic effect in a CIA rat model.

Conclusion

The FGF pathway is a critical signaling pathway in relapse RA. Targeted tissue‐specific inhibition of FGF10/FGFR1 may provide new opportunities to treat patients with relapse RA.
ALKBH5‐Mediated RNA m6A Methylation Regulates the Migration, Invasion, and Proliferation of Rheumatoid Fibroblast‐Like Synoviocytes
Authors: Kuang Yu , Li Ruiru , Wang Jingnan , Xu Siqi , Qiu Qian , Lin Shuibin , Liu Di , Shen Chuyu , Liu Yingli , Xu Meilin , Lin Wei , Zhang Shuoyang , Liang Liuqin , Xu Hanshi , Xiao Youjun
Published: August 2023

Objective

Fibroblast‐like synoviocytes (FLSs) are critical for promoting joint damage in rheumatoid arthritis (RA). N6‐methyladenosine (m6A) modification plays key roles in various diseases, but its role in the pathogenesis of RA is largely unknown. Here, we investigate increased demethylase ALKBH5 promotion of proliferation, migration, and invasion of RA FLSs via regulating JARID2 expression.

Methods

ALKBH5 expression in FLSs was evaluated using real‐time quantitative polymerase chain reaction (RT‐qPCR) and Western blot. 5‐ethynyl‐2′‐deoxyuridine, scratch wound healing, and transwell assays were implemented to determine the role of ALKBH5 on RA FLS proliferation, mobility, and migration. Then, m6A sequencing combined with RNA sequencing was performed to identify the potential targets of ALKBH5. RNA immunoprecipitation and RNA pulldown were then used to validate the interaction between the protein and messenger RNA (mRNA). Collagen‐induced arthritis (CIA) and delayed‐type hypersensitivity arthritis (DTHA) models were further established to assess the therapeutic potency of ALKBH5 in vivo.

Results

We demonstrated that ALKBH5 expression was increased in FLSs and synovium from RA. Functionally, ALKBH5 knockdown inhibited the proliferation, migration, and invasion of RA FLSs, whereas overexpression of ALKBH5 displayed the opposite effect. Mechanistically, ALKBH5 mediated m6A modification in the JARID2 mRNA and enhanced its mRNA stability in cooperation with IGF2BP3. Intriguingly, the severity of arthritis was attenuated in mice with DTHA and ALKBH5 knockout or rats with CIA and intra‐articular injection of ALKBH5 short hairpin RNA.

Conclusion

Our findings suggest that ALKBH5‐mediated m6A modification is crucial for synovial hyperplasia and invasion in RA. ALKBH5 might be a potential therapeutic target for RA and even for dysregulated fibroblasts in a wide range of diseases.

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Neural‐based online finite‐time optimal tracking control for wheeled mobile robotic system with inequality constraints
Authors: Ding Liang , Zheng Miao , Li Shu , Yang Huaiguang , Gao Haibo , Deng Zongquan
Published: August 2023

In this study, a finite‐time online optimal controller was designed for a nonlinear wheeled mobile robotic system (WMRS) with inequality constraints, based on reinforcement learning (RL) neural networks. In addition, an extended cost function, obtained by introducing a penalty function to the original long‐time cost function, was proposed to deal with the optimal control problem of the system with inequality constraints. A novel Hamilton‐Jacobi‐Bellman (HJB) equation containing the constraint conditions was defined to determine the optimal control input. Furthermore, two neural networks (NNs), a critic and an actor NN, were established to approximate the extended cost function and the optimal control input, respectively. The adaptation laws of the critic and actor NN were obtained with the gradient descent method. The semi‐global practical finite‐time stability (SGPFS) was proved using Lyapunov's stability theory. The tracking error converges to a small region near zero within the constraints in a finite period. Finally, the effectiveness of the proposed optimal controller was verified by a simulation based on a practical wheeled mobile robot model.
Patient experiences with tissue‐based genomic testing during active surveillance for prostate cancer
Authors: Leapman Michael S. , Sutherland Ryan , Gross Cary P. , Ma Xiaomei , Seibert Tyler M. , Cooperberg Matthew R. , Catalona William J. , Loeb Stacy , Schulman‐Green Dena
Published: August 2023

Background

Tissue‐based gene expression (genomic) tests provide estimates of prostate cancer aggressiveness and are increasingly used for patients considering or engaged in active surveillance. However, little is known about patient experiences with genomic testing and its role in their decision‐making.

Methods

We performed a qualitative study consisting of in‐depth, semi‐structured interviews of patients with low‐ or favourable‐intermediate‐risk prostate cancer managed with active surveillance. We purposively sampled to include patients who received biopsy‐based genomic testing as part of clinical care. The interview guide focused on experiences with genomic testing during patients' decision‐making for prostate cancer management and understanding of genomic test results. We continued interviews until thematic saturation was reached, iteratively created a code key and used conventional content analysis to analyse data.

Results

Participants' (n = 20) mean age was 68 years (range 51–79). At initial biopsy, 17 (85%) had a Gleason grade group 1, and 3 (15%) had a grade group 2 prostate cancer. The decision to undergo genomic testing was driven by both participants and physicians' recommendations; however, some participants were unaware that testing had occurred. Overall, participants understood the role of genomic testing in estimating their prostate cancer risk, and the test results increased their confidence in the decision for active surveillance. Participants had some misconceptions about the difference between tissue‐based gene expression tests and germline genetic tests and commonly believed that tissue‐based tests measured hereditary cancer risk. While some participants expressed satisfaction with their physicians' explanations, others felt that communication was limited and lacked sufficient detail.

Conclusion

Patients interact with and are influenced by the results of biopsy‐based genomic testing during active surveillance for prostate cancer, despite gaps in understanding about test results. Our findings indicate areas for improvement in patient counselling in order to increase patient knowledge and comfort with genomic testing.
Multiomics analysis reveals the biological effects of live Roseburia intestinalis as a high‐butyrate‐producing bacterium in human intestinal epithelial cells
Authors: Song Won‐Suk , Jo Sung‐Hyun , Lee Jae‐Seung , Kwon Ji‐Eun , Park Ji‐Hyeon , Kim Ye‐Rim , Baek Ji‐Hyun , Kim Min‐Gyu , Kwon Seo‐Young , Kim Yun‐Gon
Published: August 2023

Butyrate‐producing bacteria play a key role in human health, and recent studies have triggered interest in their development as next‐generation probiotics. However, there remains limited knowledge not only on the identification of high‐butyrate‐producing bacteria in the human gut but also in the metabolic capacities for prebiotic carbohydrates and their interaction with the host. Herein, it was discovered that Roseburia intestinalis produces higher levels of butyrate and digests a wider variety of prebiotic polysaccharide structures compared with other human major butyrate‐producing bacteria (Eubacterium rectale, Faecalibacterium prausnitzii, and Roseburia hominis). Moreover, R. intestinalis extracts upregulated the mRNA expression of tight junction proteins (TJP1, OCLN, and CLDN3) in human intestinal epithelial cells more than other butyrate‐producing bacteria. R. intestinalis was cultured with human intestinal epithelial cells in the mimetic intestinal host–microbe interaction coculture system to explore the health‐promoting effects using multiomics approaches. Consequently, it was discovered that live R. intestinalis only enhances purine metabolism and the oxidative pathway, increasing adenosine triphosphate levels in human intestinal epithelial cells, but that heat‐killed bacteria had no effect. Therefore, this study proposes that R. intestinalis has potentially high value as a next‐generation probiotic to promote host intestinal health.
Additional cytogenetic abnormalities in patients with newly diagnosed acute promyelocytic leukemia predict inferior event‐free survival
Authors: Zeng Hui , Dong Hai‐Bo , Zhang Qi‐Guo , Zhou Min , Zhang Qian , Chen Lan‐Xin , Yuan Cui‐Ying , Jiang Ru‐Ru , Liu Jin‐Wen , Ou‐Yang Jian , He Jie , Chen Bing
Published: August 2023

Background

The innovative combination of all‐trans retinoic acid (ATRA) and arsenic trioxide (ATO) has established a new chapter of curative approach in acute promyelocytic leukemia (APL). The disease characteristics and prognostic influence of additional cytogenetic abnormalities (ACA) in APL with modern therapeutic strategy need to be elucidated.

Methods

In the present study, we retrospectively investigated disease features and prognostic power of ACA in 171 APL patients treated with ATRA‐ATO‐containing regimens.

Results

Patients with ACA had markedly decreased hemoglobin levels than that without ACA (p = 0.021). Risk stratification in the ACA group was significantly worse than that in the non‐ACA group (p = 0.032). With a median follow‐up period of 62.0 months, worse event‐free survival (EFS) was demonstrated in patients harboring ACA. Multivariate analysis showed that ACA was an independent adverse factor for EFS (p = 0.033). By further subgroup analysis, in CD34 and CD56 negative APL, patients harboring ACA had inferior EFS (p = 0.017;p = 0.037).

Conclusions

To sum up, ACA remains the independent prognostic value for EFS, we should build risk‐adapted therapeutic strategies in the long‐term management of APL when such abnormalities are detected.
Mental health patient‐reported outcomes among adolescents and young adult cancer survivors: A systematic review
Authors: Tanner Sarah , Engstrom Teyl , Lee Wen Ray , Forbes Cheryl , Walker Rick , Bradford Natalie , Pole Jason D.
Published: August 2023

Background

Adolescent and young adult (AYA) cancer patients and survivors face significant mental health challenges throughout their cancer journey that are different to those faced by children and older adults. Patient‐reported outcome measures (PROMs) can be used to explore the experiences of AYAs, and to identify important issues and areas for potential improvement in quality of life.

Objective

We aimed to compare patient reported mental health outcomes between AYAs diagnosed with cancer and non‐cancer controls.

Method

We built on a larger systematic review of AYA cancer PROMs which searched PubMed, EMBASE, CINAHL and PsychINFO. This review identified 175 articles, which were filtered to those reporting on mental health and including a non‐cancer control group.

Results

We identified 12 eligible studies. Seven studies (58%) found those diagnosed with cancer reported poorer mental health than the non‐cancer controls. The remaining five (42%) studies found no significant difference in severity or prevalence of mental health between the AYA cancer cohort and the healthy control group. Most (83%) were cross‐sectional studies, highlighting the need for further longitudinal assessment of this group throughout their journey.

Conclusions

The mental health outcomes feature conflicting results and illustrate the need for larger studies to characterise discrepancies.
Quality criteria for pediatric oncology centers: A systematic literature review
Authors: Schladerer Sarah P. , Otth Maria , Scheinemann Katrin
Published: August 2023

Introduction

Survival of children and adolescents diagnosed with cancer improved over the last decades due to better diagnostics, treatment, and supportive care. Quality criteria that measure, compare, and make the quality of care of individual pediatric oncology centers more transparent are heterogeneous and inconsistent.

Aim

With this systematic review, we aimed to summarize existing quality criteria for pediatric oncology centers in countries with highly developed health‐care systems.

Methods

We searched three databases for publications, and websites for guidelines about quality criteria for pediatric oncology centers in February 2022. We considered all types of publications except expert opinions. We excluded publications not focusing on highly developed health‐care systems, addressing the certification of professionals, or focusing on subspecialties (e.g., pediatric neuro‐oncology). We discarded quality criteria if they were too specific (e.g., for a specific treatment center), too broad (e.g., national 5‐year overall survival), or if the aspect was covered by standardized clinical procedures or at the national level. We grouped the identified criteria thematically.

Results

We identified 18 publications and guideline documents with 530 criteria, of which 201 fulfilled the inclusion criteria. The combination of similar criteria resulted in 90 overarching criteria, which we assigned to the following categories: facilities and networks, multidisciplinary team and other experts, supportive care, treatment, long‐term care, and volume and numbers.

Conclusion

Our results provide a comprehensive overview of existing quality criteria for pediatric oncology in countries with highly developed health‐care systems. These criteria can serve as a basis to develop national quality criteria in pediatric oncology.
Association of immune checkpoint inhibitors therapy with arterial thromboembolic events in cancer patients: A retrospective cohort study
Authors: Zhu Jie , Chen Yue , Zhang Yuanlong , Wang Wei , Wang Yujue , Lu Zhuo , Zhang Yulin , Lei Haike , Li Dairong , Long Bo , Liu Haixia
Published: August 2023

Background

Immune checkpoint inhibitors (ICIs) have emerged as a standard treatment for various malignancies. However, research indicates blocking the immune checkpoint pathway may exacerbate atherosclerotic lesions.

Objectives

We aimed to investigate whether ICI therapy increases the risk of arterial thromboembolic events (ATEs).

Methods

A retrospective cohort study was conducted on patients with histologically confirmed cancer at our institution between 2018 and 2021, using the propensity score matching method. The primary endpoint was ATEs occurrence, comprising acute coronary syndrome, stroke/transient ischemic attack, and peripheral arterial thromboembolism. Subgroup analyses assessed whether the ICI treatment effect on ATEs varied over time by limiting the maximum follow‐up duration. Logistic regression analysis identified ATE risk factors in ICI‐treated patients.

Results

Overall, the ICI group (n = 2877) demonstrated an ATEs risk 2.01 times higher than the non‐ICI group (RR, 2.01 [95% CI (1.61–2.51)]; p < 0.001). Subgroup analysis revealed no significant increase in ATEs risk for ICI‐treated patients within 1 year (Limited to a max 9‐month follow‐up, p = 0.075). However, ATEs risk in the ICI group rose by 41% at 1 year (p = 0.010) and 97% at 4 years (p ≤ 0.001). Age, diabetes, hypertension, peripheral atherosclerosis, atrial fibrillation, chronic ischemic heart disease, distant cancer metastasis, and ICI treatment cycles contributed to ATEs risk elevation in ICI‐treated patients.

Conclusion

ICI‐treated patients may exhibit a higher risk of ATEs, especially after 1 year of treatment.
Simple yet (more?) effective. Venous thromboembolism risk assessment model for germ cell tumour patients receiving first‐line chemotherapy
Authors: Michalski Wojciech , Poniatowska Grażyna , Jońska‐Gmyrek Joanna , Żółciak‐Siwińska Agnieszka , Zastawna Inga , Lemiński Artur , Macios Anna , Jakubczyk Michał , Demkow Tomasz , Wiechno Paweł
Published: August 2023

Background

Germ cell tumours (GCT) are highly curable malignancies. Venous thromboembolism (VTE) is a serious complication, needing better risk assessment models (RAM).

Aim

Identification of VTE incidence and risk factors in metastatic GCT patients starting first‐line chemotherapy. Developing a RAM and comparing it to Khorana risk score (KRS) and Padua Prediction Score (PPS).

Material and methods

We retrospectively analysed GCT patients staged IS–IIIC. VTE risk factors were identified with logistic regression. Area under curve of receiver operating characteristic (AUC‐ROC), Akaike and Bayesian Information Criteria (AIC, BIC) were calculated for the developed RAM, KRS and PPS.

Results

Among 495 eligible patients, VTE occurred in 69 (13.9%), including 40 prior to chemotherapy. Vein compression (OR: 8.96; 95% CI: 2.85–28.13; p < 0.001), clinical stage IIIB‐IIIC (OR: 5.68; 95% CI: 1.82–17.70; p = 0.003) and haemoglobin concentration (OR for 1 g/dL decrease: 1.32; 95% CI: 1.03–1.67; p = 0.026) were significant in our RAM. KRS ≥ 3 (OR: 3.31; 95% CI: 1.77–6.20; p < 0.001), PPS 4–5 (OR: 3.06; 95% CI: 1.49–6.29; p = 0.002) and PPS > 5 (OR 8.05; 95% CI 3.79–17.13; p < 0.001) correlated with VTE risk. Diagnostic criteria (AUC‐ROC, AIC, BIC) for the developed RAM, KRS and PPS were (0.885; 0.567; −1641), (0.588; 0.839; −1576) and (0.700; 0.799; −1585), respectively. In the numerical score, the optimal cut‐off point for high‐risk was ≥9, with sensitivity, specificity, positive and negative predictive value of 0.78, 0.77, 0.35 and 0.96, respectively.

Conclusions

Our RAM, based on vein compression, clinical stage and haemoglobin concentration proved superior to both KRS and PPS. VTE is frequent in GCT patients.
Heterogeneous treatment effects of adjuvant therapy for patients with cervical cancer in the intermediate‐risk group
Authors: Taguchi Ayumi , Kato Kosuke , Hara Konan , Furusawa Akiko , Nakajima Yujiro , Ishizawa Chihiro , Tanikawa Michihiro , Sone Kenbun , Mori Mayuyo , Shimada Muneaki , Okamoto Aikou , Takekuma Munetaka
Published: August 2023

Background

The efficacy of adjuvant therapy for patients with cervical cancer with intermediate risk (CC‐IR) remains controversial. We examined the impact of adjuvant therapy on survival outcomes in patients with CC‐IR and evaluated the heterogeneous treatment effects (HTEs) of adjuvant therapies based on clinicopathologic characteristics.

Methods

We retrospectively analyzed a previous Japanese nationwide cohort of 6192 patients with stage IB–IIB cervical cancer who underwent radical hysterectomy. We created two pairs of propensity score‐matched treatment/control groups to investigate the treatment effects of adjuvant therapies: (1) adjuvant therapy versus non‐adjuvant therapy; (2) chemotherapy versus radiotherapy conditional on adjuvant therapy. Multivariate analyses with treatment interactions were performed to evaluate the HTEs.

Results

Among the 1613 patients with CC‐IR, 619 and 994 were in the non‐treatment and treatment groups, respectively. Survival outcomes did not differ between the two groups: 3‐year progression‐free survival (PFS) rates were 88.1% and 90.3% in the non‐treatment and treatment groups, respectively (p = 0.199). Of the patients in the treatment group, 654 and 340 received radiotherapy and chemotherapy, respectively. Patients who received chemotherapy had better PFS than those who received radiotherapy (3‐year PFS, 90.9% vs. 82.9%, p = 0.010). Tumor size was a significant factor that affected the treatment effects of chemotherapy; patients with large tumors gained better therapeutic effects from chemotherapy than those with small tumors.

Conclusion

Adjuvant therapy is optional for some patients with CC‐IR; however, chemotherapy can be recommended as adjuvant therapy, particularly for patients with large tumors.
OS and DFS are affected by different diagnostic methods and hysterectomy procedures in endometrial cancer patients: A single‐center retrospective study
Authors: Sun Haiying , Zhang Long , Fu Peiying , Liu Ronghua
Published: August 2023

Purpose

We aimed to evaluate whether hysteroscopy increases the risk of intraperitoneal dissemination or worsens the prognosis of endometrial carcinoma (EC) patients and whether radical hysterectomy (RH) improves overall survival (OS) or disease‐free survival (DFS) in patients with stage II to III EC and to investigate the effects of different procedures for identifying EC and the effects of different surgical methods on the OS and DFS of endometrial cancer patients.

Methods

Four hundred sixty‐five women with EC were included in this retrospective study. Log‐rank tests and Kaplan–Meier analysis were used for the outcome comparisons of the effects of the EC diagnostic method and different hysterectomy procedures. A Cox proportional hazards model was used for univariate regression analysis.

Results

Among the three procedures for diagnosing EC (diagnostic curettage, hysteroscopy, and hysterectomy), the incidences of fallopian tube and ovarian invasion were not significantly different (p = 0.506 and 0.066, respectively). The diagnostic methods for EC had no significant effect on OS (p = 0.577) or DFS (p = 0.294). In addition, type II RH and type III RH did not improve the prognosis of patients with FIGO stage II and III disease (log‐rank p = 0.914 and 0.810 for OS; log‐rank p = 0.707 and 0.771 for DFS, respectively).

Conclusion

Based on the current study evidence, the use of diagnostic hysteroscopy procedures is safe and does not increase the risk of fallopian tube and ovarian invasion of intraperitoneal dissemination or worsen the prognosis of EC patients. Type II and type III RH did not demonstrate a benefit for stage II‐III EC patients.
Synthesis and Anticancer Activity of Novel Derivatives of α,β‐Unsaturated Ketones Based on Oleanolic Acid: in Vitro and in Silico Studies against Prostate Cancer Cells
Authors: Şenol Halil , Ghaffari‐Moghaddam Mansour , Bulut Şeyma , Akbaş Fahri , Köse Aytekin , Topçu Gülaçtı
Published: August 2023

Herein, new derivatives of α,β‐unsaturated ketones based on oleanolic acid (4 a–i) were designed, synthesized, characterized, and tested against human prostate cancer (PC3). According to the in vitro cytotoxic study, title compounds (4 a–i) showed significantly lower toxicity toward healthy cells (HUVEC) in comparison with the reference drug doxorubicin. The compounds with the lowest IC50 values on PC3 cell lines were 4 b (7.785 μM), 4 c (8.869 μM), and 4 e (8.765 μM). The results of the ADME calculations showed that the drug‐likeness parameters were within the defined ranges according to Lipinski's and Jorgensen's rules. For the most potent compounds 4 b, 4 c, and 4 e, a molecular docking analysis using the induced fit docking (IFD) protocol was performed against three protein targets (PARP, PI3K, and mTOR). Based on the IFD scores, compound 4 b had the highest calculated affinity for PARP1, while compound 4 c had higher affinities for mTOR and PI3K. The MM‐GBSA calculations showed that the most potent compounds had high binding affinities and formed stable complexes with the protein targets. Finally, a 50 ns molecular dynamics simulation was performed to study the behavior of protein target complexes under in silico physiological conditions.
Functions and mechanism of noncoding RNA in regulation and differentiation of male mammalian reproduction
Authors: Hashemi Karoii Danial , Azizi Hossein
Published: August 2023

Noncoding RNAs (ncRNAs) are active regulators of a wide range of biological and physiological processes, including the majority of mammalian reproductive events. Knowledge of the biological activities of ncRNAs in the context of mammalian reproduction will allow for a more comprehensive and comparative understanding of male sterility and fertility. In this review, we describe recent advances in ncRNA‐mediated control of mammalian reproduction and emphasize the importance of ncRNAs in several aspects of mammalian reproduction, such as germ cell biogenesis and reproductive organ activity. Furthermore, we focus on gene expression regulatory feedback loops including hormones and ncRNA expression to better understand germ cell commitment and reproductive organ function. Finally, this study shows the role of ncRNAs in male reproductive failure and provides suggestions for further research.
The Antimicrobial Properties of PdII− and RuII−pyta Complexes**
Authors: van Niekerk Annick , Joseph M. Cassiem , Kavanagh Angela , Dinh Hue , Swarts Andrew J. , Mapolie Selwyn F. , Zuegg Johannes , Cain Amy K. , Elliott Alysha G. , Blaskovich Mark A. T. , Frei Angelo
Published: August 2023

Infections associated with antimicrobial resistance (AMR) are poised to become the leading cause of death in the next few decades, a scenario that can be ascribed to two phenomena: antibiotic over‐prescription and a lack of antibiotic drug development. The crowd‐sourced initiative Community for Open Antimicrobial Drug Discovery (CO‐ADD) has been testing research compounds contributed by researchers around the world to find new antimicrobials to combat AMR, and during this campaign has found that metallodrugs might be a promising, yet untapped source. To this end, we submitted 18 PdII− and RuII−pyridyl−1,2,3‐triazolyl complexes that were developed as catalysts to assess their antimicrobial properties. It was found that the Pd complexes, especially Pd1, possessed potent antifungal activity with MICs between 0.06 and 0.125 μg mL−1 against Candida glabrata. The in‐vitro studies were extended to in‐vivo studies in Galleria mellonella larvae, where it was established that the compounds were nontoxic. Here, we effectively demonstrate the potential of PdII−pyta complexes as antifungal agents.
Myocardial revascularization failure among patients requiring cardiac catheterization and secondary revascularization in contemporary clinical practice: Results of the REVASEC multicenter registry
Authors: Salinas Pablo , García‐Camarero Tamara , Jimenez‐Kockar Marcelo , Regueiro Ander , García‐Blas Sergio , Gomez‐Menchero Antonio E. , Ojeda Soledad , Vilchez‐Tschischke Jean Paul , Amat‐Santos Ignacio , Díez‐Gil Jose Luis , Rondán Juan , Lozano Ruiz‐Poveda Fernando , de Miguel Castro Antonio , Manzano Maria C. , Pascual‐Tejerina Virginia , Cruz‐González Ignacio , García Perez‐Velasco Javier , Fernández‐Diaz Jose A. , Escaned Javier ,   REVASEC working group (collaborators)
Published: August 2023

Background

Myocardial revascularization failure (MRF) and Secondary revascularization (SR) are contemporary interventional cardiology challenges.

Aim

To investigate the characteristics, management, and prognosis of patients with myocardial revascularization failure (MRF) and need for secondary revascularization (SR) in contemporary practice.

Methods

The REVASEC study is a prospective registry (NCT03349385), which recruited patients with prior revascularization referred for coronary angiography at 19 centers. The primary endpoint is a patient‐oriented composite (POCE) at 1 year, including death, myocardial infarction, or repeat revascularization.

Results

A total of 869 patients previously revascularized by percutaneous intervention (83%) or surgery (17%) were recruited. MRF was found in 83.7% (41.1% stent/graft failure, 32.1% progression of coronary disease, and 10.5% residual disease). SR was performed in 70.1%, preferably by percutaneous intervention (95%). The POCE rate at 1 year was 14% in the overall cohort, with 6.4% all‐cause death. In the multivariate analysis, lower POCE rates were found in the groups without MRF (9.4%) and with disease progression (11%) compared with graft/stent failure (17%) and residual disease (18%), hazard ratio 0.67 (95% confidence interval: 0.45–0.99), p = 0.043. At 1 year, the SR group had less chronic persistent angina (19% vs. 34%, p < 0.001), but a higher rate of repeat revascularization (9% vs. 2.9%, p < 0.001).

Conclusion

MRF was found in 84% of patients with prior revascularization referred for coronary angiography. Stent/graft failure and residual coronary disease were associated with a worse prognosis. SR provided better symptom control at the expense of a higher rate of new revascularization
Cooperative Bimetallic Co−Mn Catalyst: Exploiting Metallo‐Organic and Hydrogen Bonded Interactions for Rechargeable C‐/N‐Alkylation
Authors: Shivaji Padmor Manohar , Vishwakarma Palak , Tothadi Srinu , Pratihar Sanjay
Published: August 2023

Despite the progress on cobalt and manganese catalyzed C−C and C−N bond‐forming methodologies, the associated catalyst reusability remains with some unresolved issue, which needs to be addressed. Disclosed herein, a flexible multidentate proton‐responsive ligand (L) bearing 2,6‐bis(1H‐benzo[d]imidazol‐2‐yl)pyridine (BBP), 6‐(1H‐benzo[d]imidazol‐2‐yl)picolinic acid (BPA), and benzene‐1,2‐diamine (BDA) for Co/Mn‐based mono‐ and bi‐metallic supramolecular materials for C‐/N‐alkylation of alcohols. The flexible binding sites and different hydrogen bond donor‐acceptor fragments of L brings the rigidity and self‐assembling to ordered crystalline supramolecular materials, which prevented the coordinatively saturated active sites and thus providing much higher reaction efficiency and selectivity, which is highly unlikely in the case of comparable individual components. The easy synthesis, efficient reactivity and selectivity through cooperativity, broad substrate scope, and efficient recycling via recharging of metals make the catalyst and the protocol economical and sustainable. Importantly, the design strategy based on metallo‐organic hydrogen bonded coordination assembly has the potential to contribute to the development of supramolecular materials for various advanced catalytic applications.
Construction of Rings via Metal‐Catalyzed C−H Annulation with Unsymmetrical Internal Alkynes: Selectivity and Applications
Authors: Zhang Qiaoya , Chen Ci , Liu Bairong , Liu Yuan , Gao Yang , Chen Qian , Huo Yanping , Li Xianwei
Published: August 2023

Selective and concise construction of ring systems that are ubiquitous skeletons across chemistry, drugs and materials, is indispensable for human life. Of note, directed C−H annulation with alkynes for the expedient delivery of ring systems holds great importance, featuring step‐ and atom‐economy, mild conditions, and broad substrate scope. However, regioselectivity issues remained when using unsymmetrical alkynes for the directed C−H annulation. Herein, we summarized recent achievements towards solving this problem by developing directing groups, metal catalysts, and alkynes with versatile and traceless functionality that ensure the overall regioselectivity, enantioselectivity, efficiency, and synthetic application. We hope this concept will promote the further development of the precise construction of functional molecules using C−H annulation with unsymmetrical alkynes.
Optimizing the Disinfection Inactivation Efficiency in Wastewater Treatment: A Computational Fluid Dynamics Investigation of a Full‐Scale Ozonation Contactor
Authors: Elaissaoui Elmeliani Mohamed El Amine , Aguedal Hakim , Iddou Abdelkader , Alaoui Chakib , Benaissa Brahim , Belhadj Mohamed El Amine , Nguyen The-Anh , Sun Meng , Terashima Mitsuharu
Published: August 2023

The inactivation kinetics of total coliforms to increase the pathogenic removal efficiency in a full‐scale ozonation contactor in a wastewater treatment plant in Algeria is investigated. An enhanced ozone contactor design is proposed and 3D multiphase computational fluid dynamics simulations were conducted to optimize the operating parameters, including flow rates, ozone concentrations considering the treatment performance, and total operating cost. The existing design has several limitations, including poor mass‐transfer efficiency and uneven distribution of dissolved ozone. To address these issues, the optimized design includes new injection‐point settings and an increased number of diffusers. The optimized design achieved a significant improvement in mass transfer efficiency. The ozone treatment effectively reduced the total coliform counts in the wastewater samples compared to the existing design. The Chick‐Watson model predicted inactivation kinetics, with a reduction of up to 99.997 %. The practical implications of this research can significantly improve the inactivation kinetics of ozone treatments.
Biomass Simulation: Orange and Eucalyptus Waste as a Source of Essential Oils Using Solar Energy
Authors: Armenta Gálvez Jesús Manuel , Ayala Bautista José Ramón , Coronado Ortega Marcos Alberto , Montero Alpírez Gisela , Montes Núñez Daniela Guadalupe Lucía , Sagaste Bernal Carlos Alfonso
Published: August 2023

Orange processing and wood production industries generate wastes in the form of orange peel and eucalyptus leaves. These residues can be valorized as feedstocks to produce essential oils. Therefore, a simultaneous orange peel and eucalyptus leaves essential oil extraction process integrating solar energy was simulated. Biomass and essential oils were simulated by using equivalence models. The coupling of solar collectors allowed the extraction of eucalyptus essential oil, with a saving of 10 % in the total energy load.
Switchable Selectivity in the Annulation of o‐Trifluoroacetylanilines and Activated Terminal Alkynes Based on Transition Metal and Phosphine Catalysis
Authors: Mitrofanov Alexander Yu. , Murashkina Arina V. , Lyssenko Konstantin A. , Beletskaya Irina P.
Published: August 2023

In this work, we have developed selective methods for the synthesis of quinoline‐2‐carboxylates and quinoline‐3‐carboxylates as well as (indolin‐2‐ylidene)acetates through copper‐, silver‐, or phosphine‐catalyzed reaction of propiolates with 2′‐amino‐2,2,2‐trifluoroacetophenones. The approaches proposed ensure synthesis of substituted quinoline carboxylates and (indolin‐2‐ylidene)acetates in good yields. Introduction of alkynones into the reaction with 2′‐amino‐2,2,2‐trifluoroacetophenones gives acyl substituted derivatives in good yields.
Mit Licht zu grünem Wasserstoff
Authors: Tausch Michael W. , Schneidewind Jacob
Published: August 2023

Grüner Wasserstoff ist ein Hauptakteur in der Energiewende. Während im öffentlichen Diskurs der Fokus auf grünem Wasserstoff liegt, der via Photovoltaik oder Windenergie und Wasserelektrolyse produziert wird, informiert dieser Beitrag über den aktuellen Stand bei der Erforschung der direkten Wasserspaltung mit Licht. Dabei wird eingegangen auf die grundlegenden Konzepte und Prozesse in der Wasserspaltung, bisherige Umsetzungen sowie aktuelle Herausforderungen, um diese Technologie in die Anwendung zu bringen. Um die noch anstehenden Herausforderungen zu überwinden ist auch die Einbindung dieser Thematik in den Chemieunterricht notwendig. Es wird auf Experimente, digitale Medien, und Lehrkonzepte, die dafür entwickelt wurden, hingewiesen.