bluuebunny/crossref_metadata_2025_split huggingface dataset:
The associations between thyroid-related hormones and the risk of thyroid cancer: An overall and dose-response meta-analysis
Authors: Wang Zheng , Lin Yuxin , Jiang Yixian , Fu Rong , Wang Yabing , Zhang Qian 
Published: December 2022

ObjectiveThyroid cancer (TC) is one of the most common malignant tumours of the endocrine system. Thyroid-stimulating hormone (TSH) is known as being a risk factor for TC, but other thyroid-related hormones are inconsistently associated with TC. The purpose of this study was to comprehensively evaluate the relationships between thyroid-related hormones and the risk of TC.MethodsThis study utilized searches of PubMed, Embase, Web of Science and Cochrane library up to the date of March 31st, 2022. Additionally, we performed a systematic review of related original studies combining overall and dose–response meta-analyses.ResultsA total of 30, 5 and 7 articles were included in the meta-analyses of TSH, Free triiodothyronine (FT3), free thyroxine (FT4) and TC risk with 58437, 6813 and 7118 participants respectively. An increased risk of TC was associated with high TSH exposure (OR=1.28, 95% CI: 1.19-1.37, P &lt; 0.001) in the overall meta-analysis. For every 1 mU/L increase in TSH, the risk of TC increased by 16%. However, in those studies that used healthy subjects as controls, the association was not statistically significant(P=0.62). Additionally, high serum FT3 demonstrated a reduced risk of TC, with a combined OR of 0.86 in the fixed-effect model (95% CI: 0.81–0.90, P &lt; 0.001). In addition, a statistically significant increase in TC risk was found when FT4 concentrations reached a certain threshold (approximately 2.2 ng/dL) in the dose-response meta-analysis.ConclusionsSignificant associations between thyroid-related hormones and the risk of TC were found in this study. Further research is needed to understand the underlying mechanisms.
Mechanical high-intensity focused ultrasound creates unique tumor debris enhancing dendritic cell-induced T cell activation
Authors: van den Bijgaart Renske J. E. , Mekers Vera E. , Schuurmans Fabian , Raaijmakers Tonke K. , Wassink Melissa , Veltien Andor , Dumont Erik , Heerschap Arend , Fütterer Jurgen J. , Adema Gosse J. 
Published: December 2022

IntroductionIn situ tumor ablation releases a unique repertoire of antigens from a heterogeneous population of tumor cells. High-intensity focused ultrasound (HIFU) is a completely noninvasive ablation therapy that can be used to ablate tumors either by heating (thermal (T)-HIFU) or by mechanical disruption (mechanical (M)-HIFU). How different HIFU ablation techniques compare with respect to their antigen release profile, their activation of responder T cells, and their ability to synergize with immune stimuli remains to be elucidated.Methods and resultsHere, we compare the immunomodulatory effects of T-HIFU and M-HIFU ablation with or without the TLR9 agonist CpG in the ovalbumin-expressing lymphoma model EG7. M-HIFU ablation alone, but much less so T-HIFU, significantly increased dendritic cell (DC) activation in draining lymph nodes (LNs). Administration of CpG following T- or M-HIFU ablation increased DC activation in draining LNs to a similar extend. Interestingly, ex vivo co-cultures of draining LN suspensions from HIFU plus CpG treated mice with CD8+ OT-I T cells demonstrate that LN cells from M-HIFU treated mice most potently induced OT-I proliferation. To delineate the mechanism for the enhanced anti-tumor immune response induced by M-HIFU, we characterized the RNA, DNA and protein content of tumor debris generated by both HIFU methods. M-HIFU induced a uniquely altered RNA, DNA and protein profile, all showing clear signs of fragmentation, whereas T-HIFU did not. Moreover, western blot analysis showed decreased levels of the immunosuppressive cytokines IL-10 and TGF-β in M-HIFU generated tumor debris compared to untreated tumor tissue or T-HIFU.ConclusionCollectively, these results imply that M-HIFU induces a unique context of the ablated tumor material, enhancing DC-mediated T cell responses when combined with CpG.
In vitro assessment of antimicrobial, anti-inflammatory, and schistolarvicidal activity of macroalgae-based gold nanoparticles
Authors: Kamal Marwa , Abdel-Raouf Neveen , Sonbol Hana , Abdel-Tawab Heba , Abdelhameed Mohamed Sayed , Hammouda Ola , Elsayed Khaled N. M. 
Published: December 2022

There is a growing need to improve facile, eco-friendly, and cheap approaches for nanoparticle (NP) synthesis. Green protocols have been investigated for the fabrication of NPs using several natural sources as plants, algae, fungi, and bacteria. Thus, the present study proposed a rapid, convenient, and efficient biosynthesis of gold NPs (Au-NPs) using the ethanolic extracts of three macroalgae, i.e., Cystoseira myrica, C. trinodis, and Caulerpa prolifera. The reduction of Au ions and the fabrication of Au-NPs were validated using ultraviolet-visible (UV–Vis) spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), and zeta potential analysis. The produced Au-NPs were tested for their antibacterial, antifungal, anti-inflammatory, and schistolarvicidal activity. Results revealed the formation of Au-NPs with an average size of 12.6–15.5 nm and different shapes that are mainly spherical with pure crystalline nature. The strong antibacterial activities of C. trinodis– and C. myrica–based Au-NPs against E. coli (inhibition zones of 22 and 19 mm) and against Staphylococcus aureus (inhibition zones of 18 and 20.5 and mm) were recorded, respectively. On the other hand, the high antifungal activity of C. trinodis Au-NPs against Aspergillus niger and Alternaria alternate showed the inhibition zones of 18 and 17 mm, respectively. The high antifungal activity of C. trinodis Au-NPs against Candida albicans (inhibition zone 16 mm) was also recorded. Regarding anti-inflammatory and schistolarvicidal activity, Au-NPs fabricated using C. myrica showed 64.2% of the inhibitory effect on protein denaturation and recorded the highest schistolarvicidal activity against Schistosoma mansoni cercariae that sank and died after 7 min. Overall, these findings proved that macroalgal ethanolic extracts can be effectively used for the biosynthesis of Au-NPs. These Au-NPs offer a significant alternative antimicrobial, anti-inflammatory, and schistolarvicidal agents. for biomedical uses.
Study on the diversity of mental states and neuroplasticity of the brain during human-machine interaction
Authors: Zhang Teng , Zhang Xiaodong , Zhu Wenjing , Lu Zhufeng , Wang Yu , Zhang Yingjie 
Published: December 2022

IntroductionWith the increasing demand for human-machine collaboration systems, more and more attention has been paid to the influence of human factors on the performance and security of the entire system. Especially in high-risk, high-precision, and difficult special tasks (such as space station maintenance tasks, anti-terrorist EOD tasks, surgical robot teleoperation tasks, etc.), there are higher requirements for the operator’s perception and cognitive level. However, as the human brain is a complex and open giant system, the perception ability and cognitive level of the human are dynamically variable, so that it will seriously affect the performance and security of the whole system.MethodsThe method proposed in this paper innovatively explained this phenomenon from two dimensions of brain space and time and attributed the dynamic changes of perception, cognitive level, and operational skills to the mental state diversity and the brain neuroplasticity. In terms of the mental state diversity, the mental states evoked paradigm and the functional brain network analysis method during work were proposed. In terms of neuroplasticity, the cognitive training intervention paradigm and the functional brain network analysis method were proposed. Twenty-six subjects participated in the mental state evoked experiment and the cognitive training intervention experiment.ResultsThe results showed that (1) the mental state of the subjects during work had the characteristics of dynamic change, and due to the influence of stimulus conditions and task patterns, the mental state showed diversity. There were significant differences between functional brain networks in different mental states, the information processing efficiency and the mechanism of brain area response had changed significantly. (2) The small-world attributes of the functional brain network of the subjects before and after the cognitive training experiment were significantly different. The brain had adjusted the distribution of information flow and resources, reducing costs and increasing efficiency as a whole. It was demonstrated that the global topology of the cortical connectivity network was reconfigured and neuroplasticity was altered through cognitive training intervention.DiscussionIn summary, this paper revealed that mental state and neuroplasticity could change the information processing efficiency and the response mechanism of brain area, thus causing the change of perception, cognitive level and operational skills, which provided a theoretical basis for studying the relationship between neural information processing and behavior.
HRK inhibits colorectal cancer cells proliferation by suppressing the PI3K/AKT/mTOR pathway
Authors: Wang Haowei , Chen Yujia , Yuan Qinzi , Chen Lixia , Dai Peiling , Li Xuenong 
Published: December 2022

BackgroundAs one of the most common malignant tumor, colorectal cancer (CRC) continues to have a high incidence and mortality rate. HRK belongs to the BCL-2 protein family, which has been shown to have antitumor effects in prostate cancer. However, its role in colorectal cancer is not yet known.MethodsIn this study, we verified the expression levels of HRK in colorectal cancer tissues by public database search as well as immunohistochemistry. Next, we analyzed HRK expression levels in CRC tissues,adjacent non-cancerous tissues, cell lines and normal intestinal epithelial cells by qPCR and Western blotting. CCK-8 proliferation assays, transwell assays, wound healing assays, colony assays and flow cytometry were performed to clarified the effect of HRK on CRC cells. Western blotting and rescue experiments were used to determine the role of HRK in regulating PI3K/AKT/mTOR signaling pathway.ResultsHRK expression was lower in CRC tissues and cell lines. Gain and loss of function experiments showed that HRK decreased proliferation, invasion and migration of CRC cells. Low expression of HRK inhibited CRC cell apoptosis as well as activated the PI3K/AKT/mTOR signaling pathway. In addition, rapamycin inhibits the activation of PI3K/AKT/mTOR signaling pathway and reverses HRK-induced alterations in cell biological functions.ConclusionOur study demonstrates that HRK is lowly expressed in colorectal cancer tissues. And for the first time, HRK was shown to promote apoptosis and inhibit proliferation of colorectal cancer cells by inhibiting PI3K/AKT/mTOR signaling pathway. HRK represents a potential target for the treatment of CRC.
Expression, tumor immune infiltration, and prognostic impact of HMGs in gastric cancer
Authors: Wu Zhiheng , Huang Yang , Yuan Weiwei , Wu Xiong , Shi Hui , Lu Ming , Xu Aman 
Published: December 2022

BackgroundIn the past decade, considerable research efforts on gastric cancer (GC) have been expended, however, little advancement has been made owing to the lack of effective biomarkers and treatment options. Herein, we aimed to examine the levels of expression, mutations, and clinical relevance of HMGs in GC to provide sufficient scientific evidence for clinical decision-making and risk management.MethodsGC samples were obtained from The Cancer Genome Atlas (TCGA). University of California Santa Cruz (UCSC) XENA, Human Protein Atlas (HPA), Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier Plotter, cBioPortal, GeneMANIA, STRING, LinkedOmics, and DAVID databases were employed. The “ggplot2” package in the R software (×64 3.6.3) was used to thoroughly analyze the effects of HMGs. qRT-PCR was performed to assess HMG levels in GC cell lines.ResultsA total of 375 GC tissues and 32 paraneoplastic tissues were analyzed. The levels of HMGA1, HMGA2, HMGB1, HMGB2, HMGB3, HMGN1, HMGN2, and HMGN4 expression were increased in GC tissues relative to normal gastric tissues. HMGA1, HMGA2, HMGB1, HMGB2, and HMGB3 were highly expressed in GC cell lines. The OS was significantly different in the group showing low expressions of HMGA1, HMGA2, HMGB1, HMGB2, HMGB3, HMGN2, HMGN3, and HMGN5. There was a significant difference in RFS between the groups with low HMGA2, HMGB3, and high HMGN2 expression. The levels of HMGA2, HMGB3, and HMGN1 had a higher accuracy for prediction to distinguish GC from normal tissues (AUC value &gt; 0.9). HMGs were tightly associated with immune infiltration and tumor immune escape and antitumor immunity most likely participates in HMG-mediated oncogenesis in GC. GO and KEGG enrichment analyses showed that HMGs played a vital role in the cell cycle pathway.ConclusionsOur results strongly suggest a vital role of HMGs in GC. HMGA2 and HMGB3 could be potential markers for prognostic prediction and treatment targets for GC by interrupting the cell cycle pathway. Our findings might provide renewed perspectives for the selection of prognostic biomarkers among HMGs in GC and may contribute to the determination of the optimal strategy for the treatment of these patients.
A novel risk classification system based on the eighth edition of TNM frameworks for esophageal adenocarcinoma patients: A deep learning approach
Authors: Shen Qiang , Chen Hongyu 
Published: December 2022

ObjectiveTo develop and validate a deep learning predictive model with better performance in survival estimation of esophageal adenocarcinoma (EAC).MethodCases diagnosed between January 2010 and December 2018 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. A deep learning survival neural network was developed and validated based on 17 variables, including demographic information, clinicopathological characteristics, and treatment details. Based on the total risk score derived from this algorithm, a novel risk classification system was constructed and compared with the 8th edition of the tumor, node, and metastasis (TNM) staging system.ResultsOf 7,764 EAC patients eligible for the study, 6,818 (87.8%) were men and the median (interquartile range, IQR) age was 65 (58–72) years. The deep learning model generated significantly superior predictions to the 8th edition staging system on the test data set (C-index: 0.773 [95% CI, 0.757–0.789] vs. 0.683 [95% CI, 0.667–0.699]; P &lt; 0.001). Calibration curves revealed that the deep learning model was well calibrated for 1- and 3-year OS, most points almost directly distributing on the 45° line. Decision curve analyses (DCAs) showed that the novel risk classification system exhibited a more significant positive net benefit than the TNM staging system. A user-friendly and precise web-based calculator with a portably executable file was implemented to visualize the deep learning predictive model.ConclusionA deep learning predictive model was developed and validated, which possesses more excellent calibration and discrimination abilities in survival prediction of EAC. The novel risk classification system based on the deep learning algorithm may serve as a useful tool in clinical decision making given its easy-to-use and better clinical applicability.
Pre-transplant gene profiling characterization by next-generation DNA sequencing might predict relapse occurrence after hematopoietic stem cell transplantation in patients affected by AML
Authors: Metafuni Elisabetta , Amato Viviana , Giammarco Sabrina , Bellesi Silvia , Rossi Monica , Minnella Gessica , Frioni Filippo , Limongiello Maria Assunta , Pagano Livio , Bacigalupo Andrea , Sica Simona , Chiusolo Patrizia 
Published: December 2022

BackgroundIn the last decade, many steps forward have been made in acute myeloid leukemia prognostic stratification, adding next-generation sequencing techniques to the conventional molecular assays. This resulted in the revision of the current risk classification and the introduction of new target therapies.Aims and methodsWe wanted to evaluate the prognostic impact of acute myeloid leukemia (AML) mutational pattern on relapse occurrence and survival after allogeneic stem cell transplantation. A specific next-generation sequencing (NGS) panel containing 26 genes was designed for the study. Ninety-six patients studied with NGS at diagnosis were included and retrospectively studied for post-transplant outcomes.ResultsOnly eight patients did not show any mutations. Multivariate Cox regression revealed FLT3 (HR, 3.36; p=0.02), NRAS (HR, 4.78; p=0.01), TP53 (HR, 4.34; p=0.03), and WT1 (HR 5.97; p=0.005) mutations as predictive variables for relapse occurrence after transplantation. Other independent variables for relapse recurrence were donor age (HR, 0.97; p=0.04), the presence of an adverse cytogenetic risk at diagnosis (HR, 3.03; p=0.04), and the obtainment of complete remission of the disease before transplantation (HR, 0.23; p=0.001). Overall survival appeared to be affected only by grade 2–4 acute GvHD occurrence (HR, 2.29; p=0.05) and relapse occurrence (HR, 4.33; p=0.0001) in multivariate analysis.ConclusionsThe small number of patients and the retrospective design of the study might affect the resonance of our data. Although results on TP53, FLT3, and WT1 were comparable to previous reports, the interesting data on NRAS deserve attention.
Quantification of the growth suppression of HER2+ breast cancer colonies under the effect of trastuzumab and PD-1/PD-L1 inhibitor
Authors: Padmanabhan Regina , Kheraldine Hadeel , Gupta Ishita , Meskin Nader , Hamad Anas , Vranic Semir , Al Moustafa Ala-Eddin 
Published: December 2022

IntroductionImmune checkpoint blockade (ICB)-based therapy is revolutionizing cancer treatment by fostering successful immune surveillance and effector cell responses against various types of cancers. However, patients with HER2+ cancers are yet to benefit from this therapeutic strategy. Precisely, several questions regarding the right combination of drugs, drug modality, and effective dose recommendations pertaining to the use of ICB-based therapy for HER2+ patients remain unanswered.MethodsIn this study, we use a mathematical modeling-based approach to quantify the growth inhibition of HER2+ breast cancer (BC) cell colonies (ZR75) when treated with anti-HER2; trastuzumab (TZ) and anti-PD-1/PD-L1 (BMS-202) agents.Results and discussionOur data show that a combination therapy of TZ and BMS-202 can significantly reduce the viability of ZR75 cells and trigger several morphological changes. The combination decreased the cell’s invasiveness along with altering several key pathways, such as Akt/mTor and ErbB2 compared to monotherapy. In addition, BMS-202 causes dose-dependent growth inhibition of HER2+ BC cell colonies alone, while this effect is significantly improved when used in combination with TZ. Based on the in-vitro monoculture experiments conducted, we argue that BMS-202 can cause tumor growth suppression not only by mediating immune response but also by interfering with the growth signaling pathways of HER2+BC. Nevertheless, further studies are imperative to substantiate this argument and to uncover the potential crosstalk between PD-1/PD-L1 inhibitors and HER2 growth signaling pathways in breast cancer.
Outpatient monitoring of patients with multisystem inflammatory syndrome (MIS-C): A mini review
Authors: Jose Jerin Tresa , Selamet Tierney Elif Seda 
Published: December 2022

IntroductionAs we learn more about the novel multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 infection, the protocols for long-term follow-up have evolved and only some of these protocols have been published. Here, we review the current literature on follow-up guidelines in MIS-C patients.MethodsWe conducted a PUBMED search of all articles published on “MIS-C” and the term “follow-up” between 2020 and 2022. Inclusion criteria were that (1) the study was an observational study or case series, and (2) the study population included pediatric population who met the diagnostic criteria for MIS-C.ResultsThere were 206 publications on MIS-C and follow-up in the last 2 years with 11 studies that fit the inclusion criteria. These papers were representing 11 different centers and encompassed a total of 343 participants. Seven of the 11 studies had participants follow-up with their cardiologist within 1 month of discharge. Between 12% and 62% of patients within each study had depressed left ventricular ejection fraction (LVEF) at admission. At the initial follow-up visit, five studies showed a normal LVEF in all patients while the other seven studies showed 2%–13% patients continuing to have depressed LVEF. In eight of the 11 studies, 9%–52% of patients had coronary artery dilation at admission. At their initial follow-up visit, 3%–28% of patients continued to have coronary artery dilation.ConclusionThere is some institutional variation in the outpatient follow-up protocols in patients diagnosed with MIS-C. A standardized follow-up guidelines might be helpful to monitor long-term prognosis of these patients.
Interventions simultaneously promoting social participation and physical activity in community living older adults: A systematic review
Authors: Tcymbal Antonina , Abu-Omar Karim , Hartung Verena , Bußkamp Annalena , Comito Chiara , Rossmann Christin , Meinzinger Diana , Reimers Anne Kerstin 
Published: December 2022

BackgroundIn recent years, there has been a global trend toward an increase in life expectancy and the proportion of elderly people among the population. In this regard, it becomes important to promote active and healthy aging. Physical inactivity and social isolation are both risk factors of many chronic illnesses and highly prevalent in older adults. This challenges communities to develop interventions that reduce these risk factors among elderly populations. The main aims of this study were to summarize community-based interventions that aim to simultaneously promote social participation and physical activity in older adults and to examine their effects.MethodsWe performed a systematic review based on the PRISMA standards. Literature searches were conducted in six scientific databases in July 2021. Articles were included if they had an interventional design, focused on older adults living in the community and measured social participation and physical activity as an outcome. The data were summarized narratively due to the heterogeneity of studies and the variety of outcome measures.ResultsOverall, 46 articles published in English were included. The studies were grouped in (1) interventions with main focus on physical activity promotion; (2) social activities that included a physical activity component; (3) health behavior interventions/ health education interventions; (4) multicomponent interventions; (5) environmental interventions. The majority of the reviewed studies reported positive effects of interventions on physical activity and/or social participation. No study reported negative effects. Analysis of quantitative studies showed that multicomponent interventions have great positive effects on both outcomes. In qualitative studies positive effects were found regardless of intervention type.ConclusionThis review summarizes the evidence about the effects of community-based interventions that aim to promote social participation and physical activity in older adults. Multicomponent interventions seem to be most suitable for simultaneous promotion of physical activity and social participation. However, high variability in measurement methods used to assess both social participation and physical activity in the included studies made it difficult to compare studies and to indicate the most effective.Systematic review registrationwww.crd.york.ac.uk, identifier: PROSPERO [CRD42021268270].