bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Rheological Characteristic Studies of Fly-Ash-Based Geopolymer Concrete
Authors: Poloju Kiran Kumar , Annadurai Shalini , Manchiryal Ram Kishore , Goriparthi Mallikarjuna Rao , Baskar Prabu , Prabakaran Mayakrishnan , Kim Jongpil
Published: March 2023

Concrete is a versatile construction material used along with a reinforcement. Concrete is made up of binder materials and aggregates. Cement is a primary binder material used to produce conventional concrete. Carbon dioxide emissions in the atmosphere are a symptom of the issue related to Portland cement manufacture. It is estimated that one ton of cement produced releases an equal amount CO2 into atmosphere. On other hand, many industrial wastes are dumped in open spaces, leading to land pollution. Researchers have developed a construction material known as geopolymer concrete that uses industrial waste materials as a binder material to address these two issues. Excellent mechanical and durability characteristics are displayed by geopolymer concrete. For the creation of geopolymer concrete, fly ash is employed as a binder material. The drawback of utilizing fly ash is the curing method. Due to increased setting time, concrete samples require either heat curing or oven-curing. Geopolymer paste preparation is based on the type of binder materials used. In this study, GGBS is partially added with fly ash to cure specimens in ambient temperature due to presence of a higher amount calcium in GGBS. The present study investigates the consistency of geopolymer pastes, their workability, and the compressive strength of cement mortars by varying the amount of binder content (360 kg/m3 & 400 kg/m3). The molarity of NaOH was varied from 8 to 12. The ratio between binder material and alkaline to binder ratio were 0.45 and 0.50, respectively. The specimens were cured in both ambient and oven temperatures to study their strength development caused by temperature. A total of 396 specimens were cast to study the behavior of geopolymer concrete made with fly ash and GGBS (FAG). The test results revealed that the substitution of 50% GGBS with fly ash exhibited better strength properties during curing. Additionally, by increasing the binder content to 400 kg/m3, the results of 80% GGBS and 20% fly ash revealed excellent consistency among all other mixes. The oven-cured specimens showed more strength compared to specimens cured in ambient temperature, but the ambient cured specimens (ACS) attained the required strength. It was also not practically possible to cure the structural members by oven-curing in the field. The mix with 80% of GGBS and 20% fly ash can be used for construction. The required strength can also be achieved by increasing the molarity ratio.
Fostering Knowledge Collaboration in Construction Projects: The Role of BIM Application
Authors: Cheng Jiajia , Huang Lu , Jiang Lixuan , Chen Jianghong , Chen Wenwen , He Yuanping
Published: March 2023

Knowledge collaboration is beneficial for project parties to assess valuable knowledge resources from others in order to enhance their competitive advantages. However, knowledge collaboration is hampered by the special project environment and temporary structure of construction projects. Based on relational contract theory, this study employs trust and relational norms as the two relational governance mechanisms for improving knowledge collaboration. Next, this study explores the effect of relational governance mechanisms on knowledge collaboration and the moderating role of the building information modelling (BIM) application level. We collected data from 166 responses in construction projects. Our results reveal that relational norms significantly impact knowledge collaboration, which is contrary to the effect of trust. Furthermore, the BIM application level has an interactive effect with relational norms, which improves knowledge collaboration. These findings reveal that the level of BIM application significantly affects the effectiveness of relational governance mechanisms. This study suggests that project managers should help project parties to develop BIM responsibilities in order to facilitate collaborative performance.
TRPV6 Calcium Channel Targeting by Antibodies Raised against Extracellular Epitopes Induces Prostate Cancer Cell Apoptosis
Authors: Haustrate Aurélien , Shapovalov George , Spriet Corentin , Cordier Clément , Kondratskyi Artem , Noyer Lucile , Foulquier François , Prevarskaya Natalia , Lehen’kyi V’yacheslav
Published: March 2023

The TRPV6 calcium channel is known to be up-regulated in various tumors. The efforts to target the TRPV6 channel in vivo are still ongoing to propose an effective therapy against cancer. Here, we report the generation of two antibodies raised against extracellular epitopes corresponding to the extracellular loop between S1 and S2 (rb79) and the pore region (rb82). These antibodies generated a complex biphasic response with the transient activation of the TRPV6 channel. Store-operated calcium entry was consequently potentiated in the prostate cancer cell line LNCaP upon the treatment. Both rb79 and rb82 antibodies significantly decreased cell survival rate in a dose-dependent manner as compared to the control antibodies of the same isotype. This decrease was due to the enhanced cell death via apoptosis revealed using a sub-G1 peak in a cell cycle assay, TUNEL assay, and a Hoechst staining, having no effects in the PC3Mtrpv6−/− cell line. Moreover, all TUNEL-positive cells had TRPV6 membrane staining as compared to the control antibody treatment where TRPV6-positive cells were all TUNEL negative. These data clearly demonstrate that TRPV6 channel targeting using rb79 and rb82 antibodies is fatal and may be successfully used in the anticancer therapies.
Oligo-Metastatic Cancers: Putative Biomarkers, Emerging Challenges and New Perspectives
Authors: Ottaiano Alessandro , Santorsola Mariachiara , Circelli Luisa , Trotta Anna Maria , Izzo Francesco , Perri Francesco , Cascella Marco , Sabbatino Francesco , Granata Vincenza , Correra Marco , Tarotto Luca , Stilo Salvatore , Fiore Francesco , Martucci Nicola , Rocca Antonello La , Picone Carmine , Muto Paolo , Borzillo Valentina , Belli Andrea , Patrone Renato , Mercadante Edoardo , Tatangelo Fabiana , Ferrara Gerardo , Di Mauro Annabella , Scognamiglio Giosué , Berretta Massimiliano , Capuozzo Maurizio , Lombardi Angela , Galon Jérôme , Gualillo Oreste , Pace Ugo , Delrio Paolo , Savarese Giovanni , Scala Stefania , Nasti Guglielmo , Caraglia Michele
Published: March 2023

Some cancer patients display a less aggressive form of metastatic disease, characterized by a low tumor burden and involving a smaller number of sites, which is referred to as “oligometastatic disease” (OMD). This review discusses new biomarkers, as well as methodological challenges and perspectives characterizing OMD. Recent studies have revealed that specific microRNA profiles, chromosome patterns, driver gene mutations (ERBB2, PBRM1, SETD2, KRAS, PIK3CA, SMAD4), polymorphisms (TCF7L2), and levels of immune cell infiltration into metastases, depending on the tumor type, are associated with an oligometastatic behavior. This suggests that OMD could be a distinct disease with specific biological and molecular characteristics. Therefore, the heterogeneity of initial tumor burden and inclusion of OMD patients in clinical trials pose a crucial methodological question that requires responses in the near future. Additionally, a solid understanding of the molecular and biological features of OMD will be necessary to support and complete the clinical staging systems, enabling a better distinction of metastatic behavior and tailored treatments.
Epigenetic Silencing of LRP2 Is Associated with Dedifferentiation and Poor Survival in Multiple Solid Tumor Types
Authors: Rasmussen Martin Q. , Tindbæk Gitte , Nielsen Morten Muhlig , Merrild Camilla , Steiniche Torben , Pedersen Jakob Skou , Moestrup Søren K. , Degn Søren E. , Madsen Mette
Published: March 2023

More than 80% of human cancers originate in epithelial tissues. Loss of epithelial cell characteristics are hallmarks of tumor development. Receptor-mediated endocytosis is a key function of absorptive epithelial cells with importance for cellular and organismal homeostasis. LRP2 (megalin) is the largest known endocytic membrane receptor and is essential for endocytosis of various ligands in specialized epithelia, including the proximal tubules of the kidney, the thyroid gland, and breast glandular epithelium. However, the role and regulation of LRP2 in cancers that arise from these tissues has not been delineated. Here, we examined the expression of LRP2 across 33 cancer types in The Cancer Genome Atlas. As expected, the highest levels of LRP2 were found in cancer types that arise from LRP2-expressing absorptive epithelial cells. However, in a subset of tumors from these cancer types, we observed epigenetic silencing of LRP2. LRP2 expression showed a strong inverse correlation to methylation of a specific CpG site (cg02361027) in the first intron of the LRP2 gene. Interestingly, low expression of LRP2 was associated with poor patient outcome in clear cell renal cell carcinoma, papillary renal cell carcinoma, mesothelioma, papillary thyroid carcinoma, and invasive breast carcinoma. Furthermore, loss of LRP2 expression was associated with dedifferentiated histological and molecular subtypes of these cancers. These observations now motivate further studies on the functional role of LRP2 in tumors of epithelial origin and the potential use of LRP2 as a cancer biomarker.
Prognostic Value of Skeletal Muscle Loss in Patients with Hepatocellular Carcinoma Treated with Hepatic Arterial Infusion Chemotherapy
Authors: Oura Kyoko , Morishita Asahiro , Tani Joji , Nomura Takako , Manabe Takushi , Takuma Kei , Nakahara Mai , Tadokoro Tomoko , Fujita Koji , Mimura Shima , Sanomura Takayuki , Nishiyama Yoshihiro , Masaki Tsutomu
Published: March 2023

Sarcopenia-related factors, including the skeletal muscle index (SMI), are reportedly associated with prognosis in patients with hepatocellular carcinoma (HCC) receiving various treatments. However, there is no evidence relating to hepatic arterial infusion chemotherapy (HAIC). In this study, we investigated whether a low SMI was associated with worse clinical outcomes of HAIC. Seventy patients with advanced HCC were included. Clinical outcomes were compared between the decreased SMI (n = 27) and non-decreased SMI (n = 43) groups, which were classified according to changes in the SMI after 3 weeks of treatment. In the prognostic analysis, patients in the decreased SMI group had significantly shorter progression-free and overall survival (OS) than those in the non-decreased SMI group. In addition, poor nutritional status and liver function were associated with an immediate decrease in the SMI after HAIC. The therapeutic effect was worse in the decreased SMI group than in the non-decreased SMI group, although the incidence of adverse events did not significantly differ. In multivariate analysis, a decreased SMI at 3 weeks after HAIC was identified as a significant independent factor associated with OS. A decreased SMI in patients with advanced HCC undergoing HAIC was associated with poor prognosis. It is effective to monitor the SMI to evaluate general conditions and predict clinical outcomes.
Is Pediatric Melanoma Really That Different from Adult Melanoma? A Multicenter Epidemiological, Clinical and Dermoscopic Study
Authors: De Giorgi Vincenzo , Magnaterra Elisabetta , Zuccaro Biancamaria , Magi Serena , Magliulo Manfredi , Medri Matelda , Mazzoni Laura , Venturi Federico , Silvestri Flavia , Tomassini Gian Marco , Gola Massimo , Tramontana Marta , Berti Samantha , Stanganelli Ignazio , Stingeni Luca , Covarelli Piero
Published: March 2023

Purpose: To improve the diagnostic accuracy and optimal management of pediatric melanomas. Methods: We conducted a retrospective descriptive, multicenter study of the epidemiological, clinical, and dermoscopic characteristics of histopathologically proven melanomas diagnosed in patients less than 18 years old. Data on sociodemographic variables, clinical and dermoscopic characteristics, histopathology, local extension, therapy and follow-up, lymph node staging, and outcome were collected from the databases of three Italian dermatology units. We performed a clinical evaluation of the morphological characteristics of each assessed melanoma, using both classic ABCDE criteria and the modified ABCDE algorithm for pediatric melanoma to evaluate which of the two algorithms best suited our series. Results: The study population consisted of 39 patients with a histologically confirmed diagnosis of pediatric melanoma. Comparing classic ABCDE criteria with the modified ABCDE algorithm for pediatric melanomas, the modified pediatric ABCDE algorithm was less sensitive than the conventional criteria. Dermoscopically, the most frequent finding was the presence of irregular streaks/pseudopods (74.4%). When evaluating the total number of different suspicious dermoscopy criteria per lesion, 64.1% of the lesion assessments recognized two dermoscopic characteristics, 20.5% identified three, and 15.4% documented four or more assessments. Conclusions: Contrary to what has always been described in the literature, from a clinical point of view, about 95% of our cases presented in a pigmented and non-amelanotic form, and these data must be underlined in the various prevention campaigns where pediatric melanoma is currently associated with a more frequently amelanotic form. All the pediatric melanomas analyzed presented at least two dermoscopic criteria of melanoma, suggesting that this could be a key for the dermoscopic diagnosis of suspected pediatric melanoma, making it possible to reach an early diagnosis even in this age group.
MRI Radiomics and Machine Learning for the Prediction of Oncotype Dx Recurrence Score in Invasive Breast Cancer
Authors: Romeo Valeria , Cuocolo Renato , Sanduzzi Luca , Carpentiero Vincenzo , Caruso Martina , Lama Beatrice , Garifalos Dimitri , Stanzione Arnaldo , Maurea Simone , Brunetti Arturo
Published: March 2023

Aim: To non-invasively predict Oncotype DX recurrence scores (ODXRS) in patients with ER+ HER2- invasive breast cancer (IBC) using dynamic contrast-enhanced (DCE) MRI-derived radiomics features extracted from primary tumor lesions and a ML algorithm. Materials and Methods: Pre-operative DCE-MRI of patients with IBC, no history of neoadjuvant therapy prior to MRI, and for which the ODXRS was available, were retrospectively selected from a public dataset. ODXRS was obtained on histological tumor samples and considered as positive if greater than 16 and 26 in patients aged under and over 50 years, respectively. Tumor lesions were manually annotated by three independent operators on DCE-MRI images through 3D ROIs positioning. Radiomic features were therefore extracted and selected using multistep feature selection process. A logistic regression ML classifier was then employed for the prediction of ODXRS. Results: 248 patients were included, of which 87 with positive ODXRS. 166 (66%) patients were grouped in the training set, while 82 (33%) in the test set. A total of 1288 features was extracted. Of these, 1244 were excluded as 771, 82 and 391 were excluded as not stable (n = 771), not variant (n = 82), and highly intercorrelated (n = 391), respectively. After the use of recursive feature elimination with logistic regression estimator and polynomial transformation, 92 features were finally selected. In the training set, the logistic regression classifier obtained an overall mean accuracy of 60%. In the test set, the accuracy of the ML classifier was 63%, with a sensitivity of 80%, specificity of 43%, and AUC of 66%. Conclusions: Radiomics and ML applied to pre-operative DCE-MRI in patients with IBC showed promises for the non-invasive prediction of ODXRS, aiding in selecting patients who will benefit from NAC.
Conditioned Media from Head and Neck Cancer Cell Lines and Serum Samples from Head and Neck Cancer Patients Drive Catabolic Pathways in Cultured Muscle Cells
Authors: Saroul Nicolas , Tardif Nicolas , Pereira Bruno , Dissard Alexis , Montrieul Laura , Sanchez Phelipe , Salles Jérôme , Petersen Jens Erik , Jakobson Towe , Gilain Laurent , Mom Thierry , Boirie Yves , Rooyakers Olav , Walrand Stéphane
Published: March 2023

Background: The role of secreted factors from the tumor cells in driving cancer cachexia and especially muscle loss is unknown. We wanted to study both the action of secreted factors from head and neck cancer (HNC) cell lines and circulating factors in HNC patients on skeletal muscle protein catabolism. Methods: Conditioned media (CM) made from head and neck cancer cell lines and mix of sera from head and neck cancer (HNC) patients were incubated for 48 h with human myotubes. The atrophy and the catabolic pathway were monitored in myotubes. The patients were classified regarding their skeletal muscle loss observed at the outset of management. Results: Tumor CM (TCM) was able to produce atrophy on myotubes as compared with control CM (CCM). However, a mix of sera from HNC patients was not able to produce atrophy in myotubes. Despite this discrepancy on atrophy, we observed a similar regulation of the catabolic pathways by the tumor-conditioned media and mix of sera from cancer patients. The catabolic response after incubation with the mix of sera seemed to depend on the muscle loss seen in patients. Conclusion: This study found evidence that the atrophy observed in HNC patients cannot be solely explained by a deficit in food intake.
Cognitive Sparing in Proton versus Photon Radiotherapy for Pediatric Brain Tumor Is Associated with White Matter Integrity: An Exploratory Study
Authors: Mash Lisa E. , Kahalley Lisa S. , Raghubar Kimberly P. , Goodrich-Hunsaker Naomi J. , Abildskov Tracy J. , De Leon Luz A. , MacLeod Marianne , Stancel Heather , Parsons Kelley , Biekman Brian , Desai Nilesh K. , Grosshans David R. , Paulino Arnold C. , Chu Zili D. , Whitehead William E. , Okcu Mehmet Fatih , Chintagumpala Murali , Wilde Elisabeth A.
Published: March 2023

Radiotherapy for pediatric brain tumors is associated with reduced white matter structural integrity and neurocognitive decline. Superior cognitive outcomes have been reported following proton radiotherapy (PRT) compared to photon radiotherapy (XRT), presumably due to improved sparing of normal brain tissue. This exploratory study examined the relationship between white matter change and late cognitive effects in pediatric brain tumor survivors treated with XRT versus PRT. Pediatric brain tumor survivors treated with XRT (n = 10) or PRT (n = 12) underwent neuropsychological testing and diffusion weighted imaging >7 years post-radiotherapy. A healthy comparison group (n = 23) was also recruited. Participants completed age-appropriate measures of intellectual functioning, visual-motor integration, and motor coordination. Tractography was conducted using automated fiber quantification (AFQ). Fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) were extracted from 12 tracts of interest. Overall, both white matter integrity (FA) and neuropsychological performance were lower in XRT patients while PRT patients were similar to healthy control participants with respect to both FA and cognitive functioning. These findings support improved long-term outcomes in PRT versus XRT. This exploratory study is the first to directly support for white matter integrity as a mechanism of cognitive sparing in PRT.
Target Antigen Attributes and Their Contributions to Clinically Approved Antibody-Drug Conjugates (ADCs) in Haematopoietic and Solid Cancers
Authors: Esapa Benjamina , Jiang Jiexuan , Cheung Anthony , Chenoweth Alicia , Thurston David E. , Karagiannis Sophia N.
Published: March 2023

Antibody drug conjugates (ADCs) are powerful anti-cancer therapies comprising an antibody joined to a cytotoxic payload through a chemical linker. ADCs exploit the specificity of antibodies for their target antigens, combined with the potency of cytotoxic drugs, to selectively kill target antigen-expressing tumour cells. The recent rapid advancement of the ADC field has so far yielded twelve and eight ADCs approved by the US and EU regulatory bodies, respectively. These serve as effective targeted treatments for several haematological and solid tumour types. In the development of an ADC, the judicious choice of an antibody target antigen with high expression on malignant cells but restricted expression on normal tissues and immune cells is considered crucial to achieve selectivity and potency while minimising on-target off-tumour toxicities. Aside from this paradigm, the selection of an antigen for an ADC requires consideration of several factors relating to the expression pattern and biological features of the target antigen. In this review, we discuss the attributes of antigens selected as targets for antibodies used in clinically approved ADCs for the treatment of haematological and solid malignancies. We discuss target expression, functions, and cellular kinetics, and we consider how these factors might contribute to ADC efficacy.
Initiation of Antiresorptive Drug Treatment during Endocrine Therapy for Breast Cancer—A Retrospective Cohort Study of 161,492 Patients in Germany
Authors: Gremke Niklas , Griewing Sebastian , Kadys Arturas , Kostev Karel , Wagner Uwe , Kalder Matthias
Published: March 2023

Background: The aim of this retrospective cohort study was to measure the proportion of women with an initial prescription of an antiresorptive drug (bisphosphonates or denosumab) during five years of endocrine breast cancer therapy. Methods: The study included women with an initial prescription of tamoxifen (TAM) or aromatase inhibitors (AIs) between January 2016 and December 2020. Kaplan–Meier analyses were performed to show the cumulative incidence of antiresorptive drug prescription for TAM and AIs separately for four age groups. A univariable Cox proportional hazards regression model was also used to estimate the relationship between initial endocrine drug (AIs vs. TAM) and antiresorptive drug prescription. Results: Within 5 years, 14.1% of patients on AI and 6.1% on TAM received their first prescription for an antiresorptive drug (p < 0.001). The difference between AI and TAM was greatest in women ≤50 years (12.9% of AI and 2.8% of patients on TAM), and smallest in women >80 years (14.5% of AI and 10.3% of patients on TAM). The proportion of denosumab was 46.2% among AI patients vs. 29.1% among patients on TAM (p < 0.001) as alendronate was prescribed to 36.9% of AI vs. 50.0% of patients on TAM. Conclusions: Across all age groups, the cumulative incidence of antiresorptive drug prescriptions was higher in patients with BC treated with AI than those receiving TAM. Denosumab was most frequently used as an antiresorptive drug in patients treated with AI, while alendronate was administered more often in patients treated with TAM.
Lung Cancer as a Leading Cause among Paraneoplastic Non-Bacterial Thrombotic Endocarditis: A Meta-Analysis of Individual Patients’ Data
Authors: Rahouma Mohamed , Khairallah Sherif , Dabsha Anas , Elkharbotly Ismail A. M. H. , Baudo Massimo , Ismail Amr , Korani Omnia M. , Hossny Mohamed , Dimagli Arnaldo , Girardi Leonard N. , Mick Stephanie L. , Gaudino Mario
Published: March 2023

Hypercoagulability is strongly associated with cancer and may result in non-bacterial thrombotic endocarditis (NBTE). The aim of our meta-analysis was to explore the demographics and characteristics of this condition in cancer. Databases were systematically searched. The outcomes were to identify the annual trend in premortem diagnosis among the entire cohort and different subgroups and to identify differences in characteristics and survival in the considered population. A total of 121 studies with 144 patients were included. The proportion of marantic endocarditis associated with lung cancer was 0.29 (95% CI, 0.21–0.37; p < 0.001), that associated with pancreatic cancer was 0.19 (95% CI, 0.13–0.27; p < 0.001), that associated with advanced cancer stage (metastasis) was 0.69 (95% CI, 0.61–0.76; p < 0.001), and that associated with adenocarcinoma was 0.65 (95% CI, 0.56–0.72; p < 0.001). Median and 6-month overall survival (OS) were 1.3 months and 32.3%, respectively, with 6-month OS of 20.8% vs. 37.0% in lung vs. other cancers, respectively (p = 0.06) and 42.9% vs. 31.1% among those who underwent intervention vs. those who did not (p = 0.07). Cases discovered in recent years had better survival (HR = 0.98 (95% CI, 0.96–0.99; p = 0.003). While cancer-associated NBTE is a rare entity, lung cancers were the most common tumor site and are frequently associated with more advanced and metastatic cancer stages. The prognosis is dismal, especially among lung cancers.
Post-CDK 4/6 Inhibitor Therapy: Current Agents and Novel Targets
Authors: Ashai Nadia , Swain Sandra M.
Published: March 2023

Front-line therapy for advanced and metastatic hormone receptor positive (HR+), HER2 negative (HER−) advanced or metastatic breast cancer (mBC) is endocrine therapy with a CDK4/6 inhibitor (CDK4/6i). The introduction of CDK4/6i has dramatically improved progression-free survival and, in some cases, overall survival. The optimal sequencing of post-front-line therapy must be personalized to patients’ overall health and tumor biology. This paper reviews approved next lines of therapy for mBC and available data on efficacy post-progression on CDK4/6i. Given the success of endocrine front-line therapy, there has been an expansion in therapies under clinical investigation targeting the estrogen receptor in novel ways. There are also clinical trials ongoing attempting to overcome CDK4/6i resistance. This paper will review these drugs under investigation, review efficacy data when possible, and provide descriptions of the adverse events reported.
Development of a 2-(2-Hydroxyphenyl)-1H-benzimidazole-Based Fluorescence Sensor Targeting Boronic Acids for Versatile Application in Boron Neutron Capture Therapy
Authors: Kondo Naoya , Takada Shinya , Hagimori Masayori , Temma Takashi
Published: March 2023

Boron neutron capture therapy (BNCT) is an attractive approach to treating cancers. Currently, only one 10B-labeled boronoagent (Borofalan, BPA) has been approved for clinical BNCT in Japan, and methods for predicting and measuring BNCT efficacy must be established to support the development of next-generation 10B-boronoagents. Fluorescence sensors targeting boronic acids can achieve this because the amount and localization of 10B in tumor tissues directly determine BNCT efficacy; however, current sensors are nonoptimal given their slow reaction rate and weak fluorescence (quantum yield < 0.1). Herein, we designed and synthesized a novel small molecular-weight fluorescence sensor, BITQ, targeting boronic acids. In vitro qualitative and quantitative properties of BITQ were assessed using a fluorophotometer and a fluorescence microscope together with BPA quantification in blood samples. BITQ exhibited significant quantitative and selective fluorescence after reacting with BPA (post-to-pre-fluorescence ratio = 5.6; quantum yield = 0.53); the fluorescence plateaued within 1 min after BPA mixing, enabling the visualization of intracellular BPA distribution. Furthermore, BITQ quantified the BPA concentration in mouse blood with reliability comparable with that of current methods. This study identifies BITQ as a versatile fluorescence sensor for analyzing boronic acid agents. BITQ will contribute to 10B-boronoagent development and promote research in BNCT.
Non-Surgical Definitive Treatment for Operable Breast Cancer: Current Status and Future Prospects
Authors: Shibamoto Yuta , Takano Seiya
Published: March 2023

This article reviews the results of various non-surgical curative treatments for operable breast cancer. Radiotherapy is considered the most important among such treatments, but conventional radiotherapy alone and concurrent chemoradiotherapy do not achieve high cure rates. As a radiosensitization strategy, intratumoral injection of hydrogen peroxide before radiation has been investigated, and high local control rates (75–97%) were reported. The authors treated 45 patients with whole-breast radiotherapy, followed by stereotactic or intensity-modulated radiotherapy boost, with or without a radiosensitization strategy employing either hydrogen peroxide injection or hyperthermia plus oral tegafur-gimeracil-oteracil potassium. Stages were 0–I in 23 patients, II in 19, and III in 3. Clinical and cosmetic outcomes were good, with 5-year overall, progression-free, and local recurrence-free survival rates of 97, 86, and 88%, respectively. Trials of carbon ion radiotherapy are ongoing, with promising interim results. Radiofrequency ablation, focused ultrasound, and other image-guided ablation treatments yielded complete ablation rates of 20–100% (mostly ≥70%), but long-term cure rates remain unclear. In these treatments, combination with radiotherapy seems necessary to treat the extensive intraductal components. Non-surgical treatment of breast cancer is evolving steadily, with radiotherapy playing a major role. In the future, proton therapy with the ultra-high-dose-rate FLASH mode is expected to further improve outcomes.
Mapping the Protein Kinome: Current Strategy and Future Direction
Authors: Hou Zhanwu , Liu Huadong
Published: March 2023

The kinome includes over 500 different protein kinases, which form an integrated kinase network that regulates cellular phosphorylation signals. The kinome plays a central role in almost every cellular process and has strong linkages with many diseases. Thus, the evaluation of the cellular kinome in the physiological environment is essential to understand biological processes, disease development, and to target therapy. Currently, a number of strategies for kinome analysis have been developed, which are based on monitoring the phosphorylation of kinases or substrates. They have enabled researchers to tackle increasingly complex biological problems and pathological processes, and have promoted the development of kinase inhibitors. Additionally, with the increasing interest in how kinases participate in biological processes at spatial scales, it has become urgent to develop tools to estimate spatial kinome activity. With multidisciplinary efforts, a growing number of novel approaches have the potential to be applied to spatial kinome analysis. In this paper, we review the widely used methods used for kinome analysis and the challenges encountered in their applications. Meanwhile, potential approaches that may be of benefit to spatial kinome study are explored.
BAP1 Malignant Pleural Mesothelioma Mutations in Caenorhabditis elegans Reveal Synthetic Lethality between ubh-4/BAP1 and the Proteasome Subunit rpn-9/PSMD13
Authors: Martínez-Fernández Carmen , Jha Sweta , Aliagas Elisabet , Holmberg Carina I. , Nadal Ernest , Cerón Julián
Published: March 2023

The deubiquitinase BAP1 (BRCA1-associated protein 1) is associated with BAP1 tumor predisposition syndrome (TPDS). BAP1 is a tumor suppressor gene whose alterations in cancer are commonly caused by gene mutations leading to protein loss of function. By CRISPR-Cas, we have generated mutations in ubh-4, the BAP1 ortholog in Caenorhabditis elegans, to model the functional impact of BAP1 mutations. We have found that a mimicked BAP1 cancer missense mutation (UBH-4 A87D; BAP1 A95D) resembles the phenotypes of ubh-4 deletion mutants. Despite ubh-4 being ubiquitously expressed, the gene is not essential for viability and its deletion causes only mild phenotypes without affecting 20S proteasome levels. Such viability facilitated an RNAi screen for ubh-4 genetic interactors that identified rpn-9, the ortholog of human PSMD13, a gene encoding subunit of the regulatory particle of the 26S proteasome. ubh-4[A87D], similarly to ubh-4 deletion, cause a synthetic genetic interaction with rpn-9 inactivation affecting body size, lifespan, and the development of germ cells. Finally, we show how ubh-4 inactivation sensitizes animals to the chemotherapeutic agent Bortezomib, which is a proteasome inhibitor. Thus, we have established a model to study BAP1 cancer-related mutations in C. elegans, and our data points toward vulnerabilities that should be studied to explore therapeutic opportunities within the complexity of BAP1 tumors.
Revolutionizing Disease Modeling: The Emergence of Organoids in Cellular Systems
Authors: Silva-Pedrosa Rita , Salgado António José , Ferreira Pedro Eduardo
Published: March 2023

Cellular models have created opportunities to explore the characteristics of human diseases through well-established protocols, while avoiding the ethical restrictions associated with post-mortem studies and the costs associated with researching animal models. The capability of cell reprogramming, such as induced pluripotent stem cells (iPSCs) technology, solved the complications associated with human embryonic stem cells (hESC) usage. Moreover, iPSCs made significant contributions for human medicine, such as in diagnosis, therapeutic and regenerative medicine. The two-dimensional (2D) models allowed for monolayer cellular culture in vitro; however, they were surpassed by the three-dimensional (3D) cell culture system. The 3D cell culture provides higher cell–cell contact and a multi-layered cell culture, which more closely respects cellular morphology and polarity. It is more tightly able to resemble conditions in vivo and a closer approach to the architecture of human tissues, such as human organoids. Organoids are 3D cellular structures that mimic the architecture and function of native tissues. They are generated in vitro from stem cells or differentiated cells, such as epithelial or neural cells, and are used to study organ development, disease modeling, and drug discovery. Organoids have become a powerful tool for understanding the cellular and molecular mechanisms underlying human physiology, providing new insights into the pathogenesis of cancer, metabolic diseases, and brain disorders. Although organoid technology is up-and-coming, it also has some limitations that require improvements.
The LINC Complex Inhibits Excessive Chromatin Repression
Authors: Amiad Pavlov Daria , Unnikannan CP , Lorber Dana , Bajpai Gaurav , Olender Tsviya , Stoops Elizabeth , Reuveny Adriana , Safran Samuel , Volk Talila
Published: March 2023

The Linker of Nucleoskeleton and Cytoskeleton (LINC) complex transduces nuclear mechanical inputs suggested to control chromatin organization and gene expression; however, the underlying mechanism is currently unclear. We show here that the LINC complex is needed to minimize chromatin repression in muscle tissue, where the nuclei are exposed to significant mechanical inputs during muscle contraction. To this end, the genomic binding profiles of Polycomb, Heterochromatin Protein1 (HP1a) repressors, and of RNA-Pol II were studied in Drosophila larval muscles lacking functional LINC complex. A significant increase in the binding of Polycomb and parallel reduction of RNA-Pol-II binding to a set of muscle genes was observed. Consistently, enhanced tri-methylated H3K9 and H3K27 repressive modifications and reduced chromatin activation by H3K9 acetylation were found. Furthermore, larger tri-methylated H3K27me3 repressive clusters, and chromatin redistribution from the nuclear periphery towards nuclear center, were detected in live LINC mutant larval muscles. Computer simulation indicated that the observed dissociation of the chromatin from the nuclear envelope promotes growth of tri-methylated H3K27 repressive clusters. Thus, we suggest that by promoting chromatin–nuclear envelope binding, the LINC complex restricts the size of repressive H3K27 tri-methylated clusters, thereby limiting the binding of Polycomb transcription repressor, directing robust transcription in muscle fibers.
Shifting the Cancer Screening Paradigm: The Rising Potential of Blood-Based Multi-Cancer Early Detection Tests
Authors: Brito-Rocha Tiago , Constâncio Vera , Henrique Rui , Jerónimo Carmen
Published: March 2023

Cancer remains a leading cause of death worldwide, partly owing to late detection which entails limited and often ineffective therapeutic options. Most cancers lack validated screening procedures, and the ones available disclose several drawbacks, leading to low patient compliance and unnecessary workups, adding up the costs to healthcare systems. Hence, there is a great need for innovative, accurate, and minimally invasive tools for early cancer detection. In recent years, multi-cancer early detection (MCED) tests emerged as a promising screening tool, combining molecular analysis of tumor-related markers present in body fluids with artificial intelligence to simultaneously detect a variety of cancers and further discriminate the underlying cancer type. Herein, we aim to provide a highlight of the variety of strategies currently under development concerning MCED, as well as the major factors which are preventing clinical implementation. Although MCED tests depict great potential for clinical application, large-scale clinical validation studies are still lacking.
The Role of Oxidative Stress in Vitiligo: An Update on Its Pathogenesis and Therapeutic Implications
Authors: Chang Wei-Ling , Ko Chi-Hsiang
Published: March 2023

Vitiligo is an autoimmune skin disorder caused by dysfunctional pigment-producing melanocytes which are attacked by immune cells. Oxidative stress is considered to play a crucial role in activating consequent autoimmune responses related to vitiligo. Melanin synthesis by melanocytes is the main intracellular stressor, producing reactive oxygen species (ROS). Under normal physiological conditions, the antioxidative nuclear factor erythroid 2-related factor 2 (Nrf2) pathway functions as a crucial mediator for cells to resist oxidative stress. In pathological situations, such as with antioxidant defects or under inflammation, ROS accumulate and cause cell damage. Herein, we summarize events at the cellular level under excessive ROS in vitiligo and highlight exposure to melanocyte-specific antigens that trigger immune responses. Such responses lead to functional impairment and the death of melanocytes, which sequentially increase melanocyte cytotoxicity through both innate and adaptive immunity. This report provides new perspectives and advances our understanding of interrelationships between oxidative stress and autoimmunity in the pathogenesis of vitiligo. We describe progress with targeted antioxidant therapy, with the aim of providing potential therapeutic approaches.
Caveolae Mechanotransduction at the Interface between Cytoskeleton and Extracellular Matrix
Authors: Sotodosos-Alonso Laura , Pulgarín-Alfaro Marta , del Pozo Miguel A.
Published: March 2023

The plasma membrane (PM) is subjected to multiple mechanical forces, and it must adapt and respond to them. PM invaginations named caveolae, with a specific protein and lipid composition, play a crucial role in this mechanosensing and mechanotransduction process. They respond to PM tension changes by flattening, contributing to the buffering of high-range increases in mechanical tension, while novel structures termed dolines, sharing Caveolin1 as the main component, gradually respond to low and medium forces. Caveolae are associated with different types of cytoskeletal filaments, which regulate membrane tension and also initiate multiple mechanotransduction pathways. Caveolar components sense the mechanical properties of the substrate and orchestrate responses that modify the extracellular matrix (ECM) according to these stimuli. They perform this function through both physical remodeling of ECM, where the actin cytoskeleton is a central player, and via the chemical alteration of the ECM composition by exosome deposition. Here, we review mechanotransduction regulation mediated by caveolae and caveolar components, focusing on how mechanical cues are transmitted through the cellular cytoskeleton and how caveolae respond and remodel the ECM.
The Molecular Mechanism of the TEAD1 Gene and miR-410-5p Affect Embryonic Skeletal Muscle Development: A miRNA-Mediated ceRNA Network Analysis
Authors: Hu Wenping , Wang Xinyue , Bi Yazhen , Bao Jingjing , Shang Mingyu , Zhang Li
Published: March 2023

Muscle development is a complex biological process involving an intricate network of multiple factor interactions. Through the analysis of transcriptome data and molecular biology confirmation, this study aims to reveal the molecular mechanism underlying sheep embryonic skeletal muscle development. The RNA sequencing of embryos was conducted, and microRNA (miRNA)-mediated competitive endogenous RNA (ceRNA) networks were constructed. qRT-PCR, siRNA knockdown, CCK-8 assay, scratch assay, and dual luciferase assay were used to carry out gene function identification. Through the analysis of the ceRNA networks, three miRNAs (miR-493-3p, miR-3959-3p, and miR-410-5p) and three genes (TEAD1, ZBTB34, and POGLUT1) were identified. The qRT-PCR of the DE-miRNAs and genes in the muscle tissues of sheep showed that the expression levels of the TEAD1 gene and miR-410-5p were correlated with the growth rate. The knockdown of the TEAD1 gene by siRNA could significantly inhibit the proliferation of sheep primary embryonic myoblasts, and the expression levels of SLC1A5, FoxO3, MyoD, and Pax7 were significantly downregulated. The targeting relationship between miR-410-5p and the TEAD1 gene was validated by a dual luciferase assay, and miR-410-5p can significantly downregulate the expression of TEAD1 in sheep primary embryonic myoblasts. We proved the regulatory relationship between miR-410-5p and the TEAD1 gene, which was related to the proliferation of sheep embryonic myoblasts. The results provide a reference and molecular basis for understanding the molecular mechanism of embryonic muscle development.
Electrochemical Behavior and Voltammetric Determination of Two Synthetic Aroyl Amides Opioids
Authors: Capucciati Andrea , Burato Anna , Bersani Chiara , Protti Stefano , Profumo Antonella , Merli Daniele
Published: March 2023

In the present work, we describe the electrochemical behaviour of two opioids structurally related to aroyl amides of forensic interest, namely U-47700 and AH-7921. The data obtained allowed for the mise-au-point of a voltammetric determination protocol, that relies on differential pulse voltammetry (DPV) at a glassy carbon electrode in ethanol/0.1 M lithium perchlorate/0.10 M 2,6-lutidine. To apply the method to the analysis of real samples (urines), a clean-up and a preconcentration strategy by solid phase extraction (SPE) using the adsorbent Florisil have been developed. LOQ of 0.2 μg·mL−1 in urine samples with an enrichment factor of 20 and linear range from 5 to 150 μg·mL−1 were obtained.
Age and Gender Differences in Anthropometric Characteristics and Motor Performance of 3 through 6 Young Kids Aged (Pilot Study)
Authors: Atiković Almir , Čolakhodžić Ekrem , Užičanin Edin , Petković Emilija , Nožinović Mujanović Amra , Mujanović Edin , Zahirović Jasmin , Mešković Naida , Lilić Ana
Published: March 2023

Background: It is crucial to evaluate children’s motor coordination and strength to identify possible motor deficits on the right or left side of the body. However, whether a distinction exists in children aged 3–6 must be clarified. The goal of the current research was to investigate the differences in motor skills between preschool boys and girls, dominant and non-dominant hands or legs, in children of preschool age. (2) Methods: The present study was conducted on a sample of children (boys, n = 52; girls, n = 52; age range, 3–6 years). Three motor tests evaluated on both sides of the body served as the sample of factors used to measure athletic performance. Leg tapping (15 s), hand tapping (15 s), and a maximal hand grip strength (HGS) test kg. (3) Results: The study’s findings show no statistically significant variations in preschool boys’ and girls’ motor skills. Preschool girls had better results in the right leg tapping than preschool boys t (98) = 2.08; p ≤ 0.04. We found a significant difference between genders aged 3–4, 4–5, and 5–6 years. No correlation was found between the girls’ three variables and age. A small but significant positive correlation was found between dominant hand tapping and age r2 (52) = 0.21; p ≤ 0.01, dominant leg tapping and age r2 (52) = 0.20; p ≤ 0.01 and dominant HGS and age r2 (52) = 0.17; p ≤ 0.01. No noticeable differences were identified when comparing the dominant side with the non-dominant side in each group. The results show that most children prefer to use their right hand and right leg as their dominant sides. (4) Conclusion: The authors of this study focus on the functional (frequency of movements) and dynamic (differences in muscle strength between body sides) elements of asymmetry. Future studies should examine the influence of morphology on performance with the dominant or non-dominant body side.
Citation Network Analysis on the Influence of Vision on Academic Performance
Authors: Esteves Sandrina , Martinez-Perez Clara , Alvarez-Peregrina Cristina , Sánchez-Tena Miguel Ángel
Published: March 2023

Background: Proper vision is absolutely critical to children’s academic performance, as vision problems can drastically affect learning ability. Currently, the existing literature in this field is somewhat inconsistent and carries several controversies about the influence of vision on academic performance. In this study, citation networks were utilized in order to analyze the relationship between publications and authors, the most-cited publication, and the different research areas. Additionally, the most commonly utilized publication sources along with the most common research areas were also pinpointed. Methods: The aforementioned search was executed in the Web of Science database, with a time range beginning in 1941 and ending in 2022. In order to scrutinize the publications, VOSviewer, CiteSpace software, and the Citation Network Explorer were utilized for analysis about the most-cited publication and the different research areas. Results: Overall, 1342 papers were found in all fields along with 2187 citation networks. Moreover, 2020 was the year with the most publications, including 127 publications and 4 citation networks. Bull et al., published in 2008, was the most-cited work, reaching a citation index of 975. The clustering function managed to identity four groups with the most engaging research topics from researchers: motor visual skills, visual memory, the influence of vision on the different learning styles, and abnormal development of the visual system. Conclusions: In the end, the topic with the greatest interest was the influence of visual motor skills on academic performance. Ideally, this paper will assist fellow researchers in quickly noting which topics are of greatest interest and how research in this area has evolved.
ADNP Syndrome: A Qualitative Assessment of Symptoms, Therapies, and Challenges
Authors: Fastman Jarrett , Kolevzon Alexander
Published: March 2023

ADNP syndrome is a neurodevelopmental disorder characterized by autism spectrum disorder (ASD), intellectual disability, sensory reactivity symptoms, facial dysmorphisms, and a wide variety of other physical and behavioral health manifestations. Research on ADNP syndrome has been limited, and there are currently no validated tools for assessing clinical outcomes in ADNP syndrome specifically. The goal of this qualitative study was to ascertain the symptoms of ADNP syndrome based on caregiver interviews, with the primary aim of identifying areas for clinical improvement that may inform the development of outcome measures specific to ADNP syndrome. Data collection consisted of loosely structured interviews with 10 caregivers of children with ADNP syndrome, representing 6 males and 4 females of ages 4 to 17 (M = 10.1; SD = 4.2). Interviews were conducted via phone between November 2020 and April 2021. The analysis of coded interview data identified three overarching themes: symptoms, therapies, and challenges. Each theme encompasses several distinct codes, which were individually addressed. Our results could ultimately be useful in educating clinicians about ADNP syndrome, selecting or designing refined outcome measures for clinical trials, and informing efforts to increase support for caregivers.