bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental Study on Seismic Performance of Prefabricated Monolithic Concrete–Polystyrene Panel Composite Wall Panels
Authors: Zhao Kaozhong , Fan Zijia , Zhang Yuming , Xu Yufeng , Liu Sihong
Published: February 2024

A normal composite wall panel is a structural component composed of polystyrene insulation boards and concrete surface layers reinforced with steel wire mesh. It can be entirely prefabricated in a factory or constructed with the concrete surface layers cast on-site. A novel prefabricated monolithic concrete–polystyrene panel composite wall panel (CPC wall panel) is proposed in this study. The CPC panel features a middle part that is prefabricated in the factory while the reinforced concrete regions at its two side ends are cast on-site. To evaluate the seismic performance of the wall panel, 18 CPC specimens were designed, manufactured, and quasi-statically tested, through which the structural behaviors, failure mode, and load-bearing capacity were studied. In addition, the influences of the height-to-width ratio and the vertical compressive stress level on the seismic performance of the CPC panels were also investigated. The test results showed that the connectors spaced at 400 mm × 500 mm could ensure the concrete layers on both sides of the polystyrene board worked collectively under seismic conditions. When subjected to lateral loads, the interface between the newly poured concrete and the existing concrete exhibited good bonding. Moreover, the failure mode of the CPC wall panel was largely correlated to the height-to-width ratio that, for specimens having four steel bars of 12 mm diameter and a height-to-width ratio greater than 1, the flexural failure was initially developed, followed by diagonal shear failure. In specimens with a height-to-width ratio of 1, flexural and diagonal shear failures occurred almost simultaneously. For specimens with a height-to-width ratio of less than 1, the final diagonal shear failure was predominant. The longitudinal reinforcing bars at the two ends of the CPC panels could effectively improve their lateral load-bearing capacity, with the enhancement influenced by the height-to-width ratio, the vertical load applied to the wall panel, and the cross-sectional area of the steel bars. In practice, the lateral load-bearing capacity of the CPC panel can be conservatively evaluated using the calculation method of the reinforced concrete shear walls. Finally, the ductility of the CPC specimens was affected by the height-to-width ratio and the axial compressive stress level, such that the specimens with a larger height-to-width ratio and lower axial compressive stress exhibited better ductility.
The Impact of Wind-Driven Rain on Surface Waterproofed Brick Cavity Walls
Authors: D’Ayala Dina , Zhu Hengrui , Aktas Yasemin
Published: February 2024

Moisture ingress is a major cause of damage to masonry cavity walls. Products of various chemical compositions are available for wall surface treatment, aimed at reducing/eliminating water ingress. This study presents the results of full-scale wall tests designed to quantify water absorption into uninsulated and insulated brick masonry cavity walls exposed to wind-driven rain (WDR) with and without surface waterproofing. Two different waterproofing products were used: acrylic and silane–siloxane mixture. Untreated and treated walls were exposed to cycles consisting of 10 min wetting at 2.25 L/m2·min every 60 min. The results show that both treatments lead to a reduction in water ingress ranging from 90% to 97%. However, while a more consistent performance was obtained for the silane/siloxane-treated walls under repeated exposure, the results for the acrylic treatment were dominated by the original wall conditions, improved with a reapplication of the treatment. The testing protocol proposed in this study is effective in determining the performance of waterproofing treatments exposed to different levels of WDR. Both treatments prove to be effective in preventing moisture uptake in walls in moderate WDR exposure conditions, while in extreme WDR exposure conditions, the acrylic treatment is less effective.
Mechanical Properties and Microstructure of Highly Flowable Geopolymer Composites with Low-Content Polyvinyl Alcohol Fiber
Authors: Zhang Hongmei , Hu Fan , Duan Yuanfeng , Liao Jian , Yang Jiaqi
Published: February 2024

Geopolymer enhances mechanical properties with polyvinyl alcohol (PVA) fibers, but there has been limited research exploring low PVA fiber dosages for mechanical properties in 3D printing or shotcrete. This study experimentally investigated slag and fly ash-based geopolymer mixtures reinforced with 0.1%, 0.15%, and 0.2% PVA fiber by volume as well as a control group without PVA fibers. These mixtures were prepared using fly ash, quartz sand, slag powder, silica fume, and an aqueous sodium silicate solution as the alkali activator, with the addition of PVA fiber to enhance composite toughness. The mechanical properties of the composites, encompassing dog-bone tensile properties, cubic compressive strength, bending and post-bending compressive strength, and prism compressive properties, were evaluated. Significantly, specimens with 0.15% PVA fibers exhibited optimal performance, revealing a notable 28.57% increase in tensile stress, a 36.45% surge in prism compressive strain, and a 47.59% rise in tensile strain compared to fiber-free specimens. Furthermore, environmental scanning electron microscopy observations were employed to scrutinize the microscopic mechanisms of composites incorporating PVA fibers, slag, and fly ash. In comparison to fiber-free specimens, prism compressive specimens with 0.15% PVA fibers demonstrated a 27.17% increase in post-cracking loading capacity, a 44.07% increase in post-cracking ductility, a 50.00% increase in peak strain energy, and a 76.36% increase in strain energy ratio.
Green Residential Building Design Scheme Optimization Based on the Orthogonal Experiment EWM-TOPSIS
Authors: Chen Honghua , An Yun-ce
Published: February 2024

A multi-objective decision method is proposed based on the combining orthogonal test, entropy weight method (EWM) with TOPSIS (technique for order preference by similarity to an ideal solution) in this article. The method is more objective and efficient than traditional methods in the design of green residential buildings. A villa in Nanjing was taken as an example, and the cost, building energy consumption, and daylight factors were used as decision-making indexes. A total of six control factors were selected: terrain elevation, window area, building orientation, the opening ratio of exterior windows, roof structure, and window glass material. Each factor was designed with three levels. First, a design scheme index system was constructed, and the orthogonal experimental design was used to select representative design schemes. Then, the EWM and the TOPSIS method were used to determine the weight of each index, a comprehensive evaluation of the residential building design scheme was conducted, and, finally, the optimal scheme was confirmed via range analysis. The results show that the multi-objective decision-making model based on the orthogonal experiment EWM-TOPSIS is suitable for green residential building design and the optimal solution obtained is “15 m elevation, a 1200 × 1500 mm size vacuum glass, an orientation of 170° and an external window opening ratio 45% with a 40 mm thick expanded insulation board roof”.
Cuproptosis: Unraveling the Mechanisms of Copper-Induced Cell Death and Its Implication in Cancer Therapy
Authors: Springer Chloe , Humayun Danish , Skouta Rachid
Published: February 2024

Copper, an essential element for various biological processes, demands precise regulation to avert detrimental health effects and potential cell toxicity. This paper explores the mechanisms of copper-induced cell death, known as cuproptosis, and its potential health and disease implications, including cancer therapy. Copper ionophores, such as elesclomol and disulfiram, increase intracellular copper levels. This elevation triggers oxidative stress and subsequent cell death, offering potential implications in cancer therapy. Additionally, copper ionophores disrupt mitochondrial respiration and protein lipoylation, further contributing to copper toxicity and cell death. Potential targets and biomarkers are identified, as copper can be targeted to those proteins to trigger cuproptosis. The role of copper in different cancers is discussed to understand targeted cancer therapies using copper nanomaterials, copper ionophores, and copper chelators. Furthermore, the role of copper is explored through diseases such as Wilson and Menkes disease to understand the physiological mechanisms of copper. Exploring cuproptosis presents an opportunity to improve treatments for copper-related disorders and various cancers, with the potential to bring significant advancements to modern medicine.
Long-Term Results of IFRT vs. ISRT in Infradiaphragmal Fields in Aggressive Non-Hodgkins’s Lymphoma Patients—A Single Centre Experience
Authors: Galunic Bilic Lea , Santek Fedor , Mitrovic Zdravko , Basic-Kinda Sandra , Dujmovic Dino , Vodanovic Marijo , Mandac Smoljanovic Inga , Ostojic Kolonic Slobodanka , Galunic Cicak Ruzica , Aurer Igor
Published: February 2024

(1) Background: This study aimed to examine the difference in efficacy and toxicity of involved-field (IFRT) and involved-site radiotherapy (ISRT) fields in infradiaphragmal aggressive non-Hodgkin lymphoma patients. (2) Methods: In total, 140 patients with infradiaphragmal lymphoma treated between 2003 and 2020 were retrospectively evaluated. There were 69 patients (49%) treated with IFRT, and 71 (51%) patients treated with ISRT. The median dose in the IFRT group was 36 Gy, (range 4–50.4 Gy), and in the ISRT group, it was 30 Gy (range 4–48 Gy). (3) Results: The median follow-up in the IFRT group was 133 months (95% CI 109–158), and in the ISRT group, it was 48 months (95% CI 39–57). In the IFRT group, locoregional control was 67%, and in the ISRT group, 73%. The 2- and 5-year overall survival (OS) in the IFRT and ISRT groups were 79% and 69% vs. 80% and 70%, respectively (p = 0.711). The 2- and 5-year event-free survival (EFS) in the IFRT and ISRT groups were 73% and 68% vs. 77% and 70%, respectively (p = 0.575). Acute side effects occurred in 43 (31%) patients, which is more frequent in the IFRT group, 34 (39%) patients, than in the ISRT group, 9 (13%) patients, p > 0.01. Late toxicities occurred more often in the IFRT group of patients, (10/53) 19%, than in the ISRT group of patients, (2/37) 5%, (p = 0.026). (4) Conclusions: By reducing the radiotherapy volume and the doses in the treatment of infradiaphragmatic fields, treatment with significantly fewer acute and long-term side effects is possible. At the same time, efficiency and local disease control are not compromised.
Anaplastic Lymphoma Kinase (ALK) in Posterior Cranial Fossa Tumors: A Scoping Review of Diagnostic, Prognostic, and Therapeutic Perspectives
Authors: Mousa Danai-Priskila V. , Mavrovounis Georgios , Argyropoulos Dionysios , Stranjalis George , Kalamatianos Theodosis
Published: February 2024

Anaplastic Lymphoma Kinase (ALK) has been implicated in several human cancers. This review aims at mapping the available literature on the involvement of ALK in non-glial tumors localized in the posterior cranial fossa and at identifying diagnostic, prognostic, and therapeutic considerations. Following the PRISMA-ScR guidelines, studies were included if they investigated ALK’s role in primary CNS, non-glial tumors located in the posterior cranial fossa. A total of 210 manuscripts were selected for full-text review and 16 finally met the inclusion criteria. The review included 55 cases of primary, intracranial neoplasms with ALK genetic alterations and/or protein expression, located in the posterior fossa, comprising of medulloblastoma, anaplastic large-cell lymphoma, histiocytosis, inflammatory myofibroblastic tumors, and intracranial myxoid mesenchymal tumors. ALK pathology was investigated via immunohistochemistry or genetic analysis. Several studies provided evidence for potential diagnostic and prognostic value for ALK assessment as well as therapeutic efficacy in its targeting. The available findings on ALK in posterior fossa tumors are limited. Nevertheless, previous findings suggest that ALK assessment is of diagnostic and prognostic value in medulloblastoma (WNT-activated). Interestingly, a substantial proportion of ALK-positive/altered CNS histiocytoses thus far identified have been localized in the posterior fossa. The therapeutic potential of ALK inhibition in histiocytosis warrants further investigation.
Comparison of PIV and Other Immune Inflammation Markers of Oncological and Survival Outcomes in Patients Undergoing Radical Cystectomy
Authors: Russo Pierluigi , Palermo Giuseppe , Iacovelli Roberto , Ragonese Mauro , Ciccarese Chiara , Maioriello Giuseppe , Fantasia Fabrizio , Bizzarri Francesco Pio , Marino Filippo , Moosavi Koosha , Nigro Domenico , Filomena Giovanni Battista , Gavi Filippo , Rossi Francesco , Pinto Francesco , Racioppi Marco , Foschi Nazario
Published: February 2024

Inflammation is widely acknowledged as a significant characteristic of cancer, playing a substantial function in both the initiation and advancement of cancers. In this research, we planned to compare pan-immune inflammation markers and other well-known markers (systemic immune inflammation index and neutrophil to lymphocyte ratio) to predict prognosis in individuals treated with radical cystectomy for bladder cancer. Methods: In this retrospective analysis, we focused on preoperative PIV, systemic immune inflammation index (SII), and neutrophil–lymphocyte ratio (NLR) in 193 individuals managed with radical cystectomy for bladder cancer between January 2016 and November 2022. Multivariable logistic regression assessments were performed to assess the predictive capabilities of PIV, SII, and NLR for infiltration of lymph nodes (N), aggressive tumor stage (pT3/pT4), and any non-organ limited disease at the time of RC. Multivariable Cox regression analyses were conducted to assess the predictive impact of PIV on Relapse-free survival (RFS), Cancer-specific survival (CSS), and Overall survival (OS). Results: Our individuals were divided into high PIV and low PIV cohorts using the optimal cut-off value (340.96 × 109/L) based on receiver operating characteristic curve analysis for relapse-free survival. In multivariable preoperative logistic regression models, only SII and PIV correlated with the infiltration of lymph nodes, aggressive disease, and any non-organ confined disease. In multivariable Cox regression models considering presurgical clinicopathological variables, a higher PIV was associated with diminished RFS (p = 0.017) and OS (p = 0.029). In addition, in multivariable Cox regression models for postoperative outcomes, a high PIV correlated with both RFS (p = 0.034) and OS (p = 0.048). Conclusions: Our study suggests that PIV and SII are two very similar markers that may serve as independent and significant predictors of aggressive disease and worse survival impacts on individuals undergoing radical cystectomy for bladder neoplasm.
Role of Post-Translational Modifications in Colorectal Cancer Metastasis
Authors: Peng Na , Liu Jingwei , Hai Shuangshuang , Liu Yihong , Zhao Haibo , Liu Weixin
Published: February 2024

Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive tract. CRC metastasis is a multi-step process with various factors involved, including genetic and epigenetic regulations, which turn out to be a serious threat to CRC patients. Post-translational modifications (PTMs) of proteins involve the addition of chemical groups, sugars, or proteins to specific residues, which fine-tunes a protein’s stability, localization, or interactions to orchestrate complicated biological processes. An increasing number of recent studies suggest that dysregulation of PTMs, such as phosphorylation, ubiquitination, and glycosylation, play pivotal roles in the CRC metastasis cascade. Here, we summarized recent advances in the role of post-translational modifications in diverse aspects of CRC metastasis and its detailed molecular mechanisms. Moreover, advances in drugs targeting PTMs and their cooperation with other anti-cancer drugs, which might provide novel targets for CRC treatment and improve therapeutic efficacy, were also discussed.
Lymphedema and Trismus after Head and Neck Cancer, and the Impact on Body Image and Quality of Life
Authors: Arends Coralie R. , van der Molen Lisette , Lindhout Josephine E. , Bragante Karoline , Navran Arash , van den Brekel Michiel W. M. , Stuiver Martijn M.
Published: February 2024

Background: To assess the prevalence of chronic lymphedema and trismus in patients > 6 months after head and neck cancer (HNC) treatment, and to explore how the severity of these conditions correlates with body image and quality of life. Methods: The cross-sectional sample included 59 patients, treated for HNC between six months to three years ago. Physical measurements were performed to assess the presence of external lymphedema and trismus (<36 mm). Furthermore, participants completed two questionnaires regarding body image (BIS) and quality of life (UW-QoL V4). Results: Lymphedema prevalence was 94.1% (95% CI 0.86–0.98), with a median severity score of 9 (range 0–24). Trismus prevalence in this sample was 1.2%. The median BIS score was 2, indicating a positive body image. The UW-QoL score showed a good QOL with a median of 100. Only the domain of saliva and overall related health had a lower median of 70 and 60, respectively. There was no correlation between lymphedema and body image (r = 0.08, p = 0.544). Patients with higher lymphedema scores reported poorer speech with a moderate correlation (r = −0.39, p = 0.003). Conclusion: Lymphedema is a highly prevalent, but moderately severe late side-effect of HNC with a limited impact on quality of life domains except for speech, in our cohort.
miR-622 Increases miR-30a Expression through Inhibition of Hypoxia-Inducible Factor 1α to Improve Metastasis and Chemoresistance in Human Invasive Breast Cancer Cells
Authors: Cheng Chun-Wen , Liu Yu-Fan , Liao Wen-Ling , Chen Po-Ming , Hung Yueh-Tzu , Lee Huei-Jane , Cheng Yu-Chun , Wu Pei-Ei , Lu Yen-Shen , Shen Chen-Yang
Published: February 2024

Hypoxia-inducible factor 1α (HIF-1α) plays a pivotal role in the survival, metastasis, and response to treatment of solid tumors. Autophagy serves as a mechanism for tumor cells to eliminate misfolded proteins and damaged organelles, thus promoting invasiveness, metastasis, and resistance to treatment under hypoxic conditions. MicroRNA (miRNA) research underscores the significance of these non-coding molecules in regulating cancer-related protein synthesis across diverse contexts. However, there is limited reporting on miRNA-mediated gene expression studies, especially with respect to epithelial–mesenchymal transition (EMT) and autophagy in the context of hypoxic breast cancer. Our study reveals decreased levels of miRNA-622 (miR-622) and miRNA-30a (miR-30a) in invasive breast cancer cells compared to their non-invasive counterparts. Inducing miR-622 suppresses HIF-1α protein expression, subsequently activating miR-30a transcription. This cascade results in reduced invasiveness and migration of breast cancer cells by inhibiting EMT markers, such as Snail, Slug, and vimentin. Furthermore, miR-30a negatively regulates beclin 1, ATG5, and LC3-II and inhibits Akt protein phosphorylation. Consequently, this improves the sensitivity of invasive MDA-MB-231 cells to docetaxel treatment. In conclusion, our study highlights the therapeutic potential of inducing miR-622 to promote miR-30a expression and thus disrupt HIF-1α-associated EMT and autophagy pathways. This innovative strategy presents a promising approach to the treatment of aggressive breast cancer.
Cell-Free DNA: Unveiling the Future of Cancer Diagnostics and Monitoring
Authors: Francini Edoardo , Nuzzo Pier Vitale , Fanelli Giuseppe Nicolò
Published: February 2024

As we conclude this Special Issue of 21 published articles dedicated to cell-free DNA (cfDNA) as a prognostic and predictive biomarker in solid cancers, we find ourselves gazing at a vibrant landscape of research on cfDNA [...]
MicroRNAs Associated with Androgen Receptor and Metastasis in Triple-Negative Breast Cancer
Authors: Ahram Mamoun , Abu Alragheb Bayan , Abushukair Hassan , Bawadi Randa , Al-Hussaini Maysa
Published: February 2024

It is crucial to identify novel molecular biomarkers and therapeutic targets for triple-negative breast cancer (TNBC). The androgen receptor (AR) is a regulator of TNBC, acting partially via microRNA molecules (miRNAs). In this study, we used PCR arrays to profile the expression of 84 miRNAs in 24 TNBC tissue samples, which were equally classified according to AR expression and/or metastasis. Several bioinformatics tools were then utilized to determine the potentially affected protein targets and signaling pathways. Seven miRNAs were found to be significantly more highly expressed in association with AR expression, including miR-328-3p and miR-489-3p. Increased expression of miR-205-3p was found to be significantly associated with metastasis. Certain miRNAs were specifically found to be differentially expressed in either metastatic or non-metastatic AR-positive tumors. A gene ontology (GO) analysis indicated biological roles in the regulation of transcription, cellular response to DNA damage, and the transforming growth factor-beta (TGF-beta) signaling pathway. The GO analysis also showed enrichment in kinase and transcription factor activities. The TGF-beta and a number of kinase-dependent pathways were also retrieved using the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. This study offers an understanding of the role of AR in TNBC and further implicates miRNAs in mediating the effects of AR on TNBC.
An Accelerated Failure Time Model to Predict Cause-Specific Survival and Prognostic Factors of Lung and Bronchus Cancer Patients with at Least Bone or Brain Metastases: Development and Internal Validation Using a SEER-Based Study
Authors: Awodutire Phillip Oluwatobi , Kattan Michael W. , Ilori Oluwatosin Stephen , Ilori Oluwatosin Ruth
Published: February 2024

Background: This study addresses the significant challenge of low survival rates in patients with cause-specific lung cancer accompanied by bone or brain metastases. Recognizing the critical need for an effective predictive model, the research aims to establish survival prediction models using both parametric and non-parametric approaches. Methods: Clinical data from lung cancer patients with at least one bone or brain metastasis between 2000 and 2020 from the SEER database were utilized. Four models were constructed: Cox proportional hazard, Weibull accelerated failure time (AFT), log-normal AFT, and Zografos–Balakrishnan log-normal (ZBLN). Independent prognostic factors for cause-specific survival were identified, and model fit was evaluated using Akaike’s and Bayesian information criteria. Internal validation assessed predictive accuracy and discriminability through the Harriel Concordance Index (C-index) and calibration plots. Results: A total of 20,412 patients were included, with 14,290 (70%) as the training cohort and 6122 (30%) validation. Independent prognostic factors selected for the study were age, race, sex, primary tumor site, disease grade, total malignant tumor in situ, metastases, treatment modality, and histology. Among the accelerated failure time (AFT) models considered, the ZBLN distribution exhibited the most robust model fit for the 3- and 5-year survival, as evidenced by the lowest values of Akaike’s information criterion of 6322 and 79,396, and the Bayesian information criterion of 63,495 and 79,396, respectively. This outperformed other AFT and Cox models (AIC = [156,891, 211,125]; BIC = [158,848, 211,287]). Regarding predictive accuracy, the ZBLN AFT model achieved the highest concordance C-index (0.682, 0.667), a better performance than the Cox model (0.669, 0.643). The calibration curves of the ZBLN AFT model demonstrated a high degree of concordance between actual and predicted values. All variables considered in this study demonstrated significance at the 0.05 level for the ZBLN AFT model. However, differences emerged in the significant variations in survival times between subgroups. The study revealed that patients with only bone metastases have a higher chance of survival compared to only brain and those with bone and brain metastases. Conclusions: The study highlights the underutilized but accurate nature of the accelerated failure time model in predicting lung cancer survival and identifying prognostic factors. These findings have implications for individualized clinical decisions, indicating the potential for screening and professional care of lung cancer patients with at least one bone or brain metastasis in the future.
Safety, Efficacy, and Immunogenicity of Therapeutic Vaccines for Patients with High-Grade Cervical Intraepithelial Neoplasia (CIN 2/3) Associated with Human Papillomavirus: A Systematic Review
Authors: Gonçalves Caroline Amélia , Pereira-da-Silva Gabriela , Silveira Renata Cristina Campos Pereira , Mayer Paulo César Morales , Zilly Adriana , Lopes-Júnior Luís Carlos
Published: February 2024

Despite the knowledge that HPV is responsible for high-grade CIN and cervical cancer, little is known about the use of therapeutic vaccines as a treatment. We aimed to synthesize and critically evaluate the evidence from clinical trials on the safety, efficacy, and immunogenicity of therapeutic vaccines in the treatment of patients with high-grade CIN associated with HPV. A systematic review of clinical trials adhering to the PRISMA 2020 statement in MEDLINE/PubMed, Embase, CENTRAL Cochrane, Web of Science, Scopus, and LILACS was undertaken, with no data or language restrictions. Primary endpoints related to the safety, efficacy, and immunogenicity of these vaccines were assessed by reviewing the adverse/toxic effects associated with the therapeutic vaccine administration via histopathological regression of the lesion and/or regression of the lesion size and via viral clearance and through the immunological response of individuals who received treatment compared to those who did not or before and after receiving the vaccine, respectively. A total of 1184 studies were identified, and 16 met all the criteria. Overall, the therapeutic vaccines were heterogeneous regarding their formulation, dose, intervention protocol, and routes of administration, making a meta-analysis unfeasible. In most studies (n = 15), the vaccines were safe and well tolerated, with clinical efficacy regarding the lesions and histopathological regression or viral clearance. In addition, eleven studies showed favorable immunological responses against HPV, and seven studies showed a positive correlation between immunogenicity and the clinical response, indicating promising results that should be further investigated. In summary, therapeutic vaccines, although urgently needed to avoid progression of CIN 2/3 patients, still present sparse data, requiring greater investments in a well-designed phase III RCT.
Oligometastasis of Gastric Cancer: A Review
Authors: Yasufuku Itaru , Tsuchiya Hiroshi , Fujibayashi Seito , Okumura Naoki , Sengoku Yuki , Fukada Masahiro , Asai Ryuichi , Sato Yuta , Tajima Jesse Yu , Kiyama Shigeru , Kato Takazumi , Tanaka Yoshihiro , Murase Katsutoshi , Matsuhashi Nobuhisa
Published: February 2024

The concept of oligometastasis is not yet fully established in the field of gastric cancer. However, metastatic lesions that are localized, technically resectable at diagnosis, present a certain response to preoperative chemotherapy, and present favorable survival outcomes with local treatments, sometimes in combination with chemotherapy, are recognized as oligometastasis in the field of gastric cancer. Oligometastasis is noted in European Society for Medical Oncology guidelines and Japanese gastric cancer treatment guidelines, and local treatment is mentioned as one of the pivotal treatment options for oligometastasis. Solitary liver metastasis or a small number of liver metastases; retroperitoneal lymph node metastasis, especially localized para-aortic lymph node metastasis; localized peritoneal dissemination; and Krukenberg tumor are representative types of oligometastasis in gastric cancer. The AIO-FLOT3 trial prospectively evaluated the efficacy of multimodal treatments for gastric cancer with oligometastasis, including surgical resection of primary and metastatic lesions combined with chemotherapy, confirming favorable survival outcomes. Two phase 3 studies are ongoing to investigate the efficacy of surgical resection combined with perioperative chemotherapy compared with palliative chemotherapy. Thus far, the evidence suggests that multimodal treatment for oligometastasis of gastric cancer is promising.
AI-Driven Models for Diagnosing and Predicting Outcomes in Lung Cancer: A Systematic Review and Meta-Analysis
Authors: Kanan Mohammed , Alharbi Hajar , Alotaibi Nawaf , Almasuood Lubna , Aljoaid Shahad , Alharbi Tuqa , Albraik Leen , Alothman Wojod , Aljohani Hadeel , Alzahrani Aghnar , Alqahtani Sadeem , Kalantan Razan , Althomali Raghad , Alameen Maram , Mufti Ahdab
Published: February 2024

(1) Background: Lung cancer’s high mortality due to late diagnosis highlights a need for early detection strategies. Artificial intelligence (AI) in healthcare, particularly for lung cancer, offers promise by analyzing medical data for early identification and personalized treatment. This systematic review evaluates AI’s performance in early lung cancer detection, analyzing its techniques, strengths, limitations, and comparative edge over traditional methods. (2) Methods: This systematic review and meta-analysis followed the PRISMA guidelines rigorously, outlining a comprehensive protocol and employing tailored search strategies across diverse databases. Two reviewers independently screened studies based on predefined criteria, ensuring the selection of high-quality data relevant to AI’s role in lung cancer detection. The extraction of key study details and performance metrics, followed by quality assessment, facilitated a robust analysis using R software (Version 4.3.0). The process, depicted via a PRISMA flow diagram, allowed for the meticulous evaluation and synthesis of the findings in this review. (3) Results: From 1024 records, 39 studies met the inclusion criteria, showcasing diverse AI model applications for lung cancer detection, emphasizing varying strengths among the studies. These findings underscore AI’s potential for early lung cancer diagnosis but highlight the need for standardization amidst study variations. The results demonstrate promising pooled sensitivity and specificity of 0.87, signifying AI’s accuracy in identifying true positives and negatives, despite the observed heterogeneity attributed to diverse study parameters. (4) Conclusions: AI demonstrates promise in early lung cancer detection, showing high accuracy levels in this systematic review. However, study variations underline the need for standardized protocols to fully leverage AI’s potential in revolutionizing early diagnosis, ultimately benefiting patients and healthcare professionals. As the field progresses, validated AI models from large-scale perspective studies will greatly benefit clinical practice and patient care in the future.
The Impact of the Gut Microbiome, Environment, and Diet in Early-Onset Colorectal Cancer Development
Authors: Dai Rui , Kelly Bridget N. , Ike Amarachi , Berger David , Chan Andrew , Drew David A. , Ljungman David , Mutiibwa David , Ricciardi Rocco , Tumusiime Gerald , Cusack James C.
Published: February 2024

Traditionally considered a disease common in the older population, colorectal cancer is increasing in incidence among younger demographics. Evidence suggests that populational- and generational-level shifts in the composition of the human gut microbiome may be tied to the recent trends in gastrointestinal carcinogenesis. This review provides an overview of current research and putative mechanisms behind the rising incidence of colorectal cancer in the younger population, with insight into future interventions that may prevent or reverse the rate of early-onset colorectal carcinoma.
Increased PIEZO1 Expression Is Associated with Worse Clinical Outcomes in Hormone-Receptor-Negative Breast Cancer Patients
Authors: Poole Rylee Ann , Wang Qingfei , Ray Alo , Takabe Kazuaki , Opyrchal Mateusz , Katsuta Eriko
Published: February 2024

PIEZO1 plays a crucial role in the human body as a mechanosensory ion channel. It has been demonstrated that PIEZO1 is important in tissue development and regulating many essential physiological processes. Studies have suggested that the PIEZO1 ion channel plays a role in invasion and progression in cancer; elevated levels of PIEZO1 have been correlated with increased migration in breast cancer cells, chemo-resistance and invasion in gastric cancer cells, and increased invasion of osteosarcoma cells. In addition, high PIEZO1 expression levels were correlated with a worse prognosis in glioma patients. On the other hand, studies in lung cancer have attributed high PIEZO1 levels to better patient outcomes. However, the clinical impact of PIEZO1 in breast cancer is not well characterized. Therefore, our goal was to determine the clinical relevance of PIEZO1 in breast cancer. An analysis of breast cancer data from The Cancer Genome Atlas (TCGA) was conducted to investigate PIEZO1 expression levels and correlation to survival, followed by validation in an independent dataset, GSE3494. We also performed gene set enrichment analysis (GSEA) and pathway enrichment analysis. We also analyzed the immune cell composition in breast tumors from TCGA through a CIBERSORT algorithm. Our results demonstrated that the PIEZO1 expression levels are higher in hormone-receptor (HR)-negative than in HR-positive cohorts. High PIEZO1 expression is correlated with a significant decrease in survival in HR-negative cohorts, especially in triple-negative breast cancer (TNBC), suggesting that PIEZO1 could be utilized as a prognostic biomarker in HR-negative breast cancer. GSEA showed that various signaling pathways associated with more invasive phenotypes and resistance to treatments, including epithelial–mesenchymal transition (EMT), hypoxia, and multiple signaling pathways, are enriched in high-PIEZO1 HR-negative tumors. Our results also demonstrated a decrease in CD8+ and CD4+ T cell infiltration in high-PIEZO1 HR-negative tumors. Further investigations are necessary to elucidate the mechanistic roles of PIEZO1 in HR-negative breast cancer.
Projected Incidence of Hepatobiliary Cancers and Trends Based on Age, Race, and Gender in the United States
Authors: Storandt Michael H. , Tella Sri Harsha , Wieczorek Mikolaj A. , Hodge David , Elrod Julia K. , Rosenberg Philip S. , Jin Zhaohui , Mahipal Amit
Published: February 2024

Background: Identifying the projected incidence of hepatobiliary cancers and recognizing patient cohorts at increased risk can help develop targeted interventions and resource allocation. The expected incidence of subtypes of hepatobiliary cancers in different age groups, races, and genders remains unknown. Methods: Historical epidemiological data from the Surveillance, Epidemiology, and End Results (SEER) database was used to project future incidence of hepatobiliary malignancies in the United States and identify trends by age, race, and gender. Patients ≥18 years of age diagnosed with a hepatobiliary malignancy between 2001 and 2017 were included. US Census Bureau 2017 National Population projects provided the projected population from 2017 to 2029. Age–Period–Cohort forecasting model was used to estimate future births cohort-specific incidence. All analyses were completed using R Statistical Software. Results: We included 110381 historical patients diagnosed with a hepatobiliary malignancy between 2001 and 2017 with the following subtypes: hepatocellular cancer (HCC) (68%), intrahepatic cholangiocarcinoma (iCCA) (11.5%), gallbladder cancer (GC) (8%), extrahepatic cholangiocarcinoma (eCCA) (7.6%), and ampullary cancer (AC) (4%). Our models predict the incidence of HCC to double (2001 to 2029) from 4.5 to 9.03 per 100,000, with the most significant increase anticipated in patients 70–79 years of age. In contrast, incidence is expected to continue to decline among the Asian population. Incidence of iCCA is projected to increase, especially in the white population, with rates in 2029 double those in 2001 (2.13 vs. 0.88 per 100,000, respectively; p < 0.001). The incidence of GC among the black population is expected to increase. The incidence of eCCA is expected to significantly increase, especially among the Hispanic population, while that of AC will remain stable. Discussion: The overall incidence of hepatobiliary malignancies is expected to increase in the coming years, with certain groups at increased risk. These findings may help with resource allocation when considering screening, treatment, and research in the coming years.
Correction: Mukherjee et al. Homo and Heterotypic Cellular Cross-Talk in Epithelial Ovarian Cancer Impart Pro-Tumorigenic Properties through Differential Activation of the Notch3 Pathway. Cancers 2022, 14, 3365
Authors: Mukherjee Souvik , Sakpal Asmita , Mehrotra Megha , Phadte Pratham , Rekhi Bharat , Ray Pritha
Published: February 2024

In the original publication [...]
Dosimetric Impact of Voluntary Deep Inspiration Breath Hold (DIBH) in Mediastinal Hodgkin Lymphomas: A Comparative Evaluation of Three Different Intensity Modulated Radiation Therapy (IMRT) Delivery Methods Using Voluntary DIBH and Free Breathing Techniques
Authors: Mohanty Samarpita , Patil Divya , Joshi Kishore , Gamre Poonam , Mishra Ajay , Khairnar Sunil , Kakoti Sangeeta , Nayak Lingaraj , Punatar Sachin , Jain Jeevanshu , Phurailatpam Reena , Goda Jayant S.
Published: February 2024

Hodgkin lymphomas are radiosensitive and curable tumors that often involve the mediastinum. However, the application of radiation therapy to the mediastinum is associated with late effects including cardiac and pulmonary toxicities and secondary cancers. The adoption of conformal IMRT and deep inspiration breath- hold (DIBH) can reduce the dose to healthy normal tissues (lungs, heart and breast). We compared the dosimetry of organs at risk (OARs) using different IMRT techniques for two breathing conditions, i.e., deep inspiration breath hold (DIBH) and free breathing. Twenty-three patients with early-stage mediastinal Hodgkin lymphomas were accrued in the prospective study. The patients were given treatment plans which utilized full arc volumetric modulated arc therapy (F-VMAT), Butterfly VMAT (B-VMAT), and fixed field IMRT (FF-IMRT) techniques for both DIBH and free breathing methods, respectively. All the plans were optimized to deliver 95% of the prescription dose which was 25.2 Gy to 95% of the PTV volume. The mean dose and standard error of the mean for each OAR, conformity index (CI), and homogeneity index (HI) for the target using the three planning techniques were calculated and compared using Student’s t-test for parametric data and Wilcoxon signed-rank test for non-parametric data. The HI and CI of the target was not compromised using the DIBH technique for mediastinal lymphomas. The mean values of CI and HI for both DIBH and FB were comparable. The mean heart doses were reduced by 2.1 Gy, 2.54 Gy, and 2.38 Gy in DIBH compared to FB for the F-VMAT, B-VMAT, and IMRT techniques, respectively. There was a significant reduction in V5Gy, V10Gy, and V15Gy to the heart (p < 0.005) with DIBH. DIBH reduced the mean dose to the total lung by 1.19 Gy, 1.47 Gy, and 1.3 Gy, respectively. Among the 14 female patients, there was a reduction in the mean right breast dose with DIBH compared to FB (4.47 Gy vs. 3.63 Gy, p = 0.004). DIBH results in lower heart, lung, and breast doses than free breathing in mediastinal Hodgkin Lymphoma. Among the different IMRT techniques, FF-IMRT, B-VMAT, and F-VMAT showed similar PTV coverage, with similar conformity and homogeneity indices. However, the time taken for FF-IMRT was much longer than for the F-VMAT and B-VMAT techniques for both breathing methods. B-VMAT and F-VMAT emerged as the optimal planning techniques able to achieve the best target coverage and lower doses to the OARs, with less time required to deliver the prescribed dose.
Kaposi’s Sarcoma: Evaluation of Clinical Features, Treatment Outcomes, and Prognosis in a Single-Center Retrospective Case Series
Authors: Russo Irene , Marino Dario , Cozzolino Claudia , Del Fiore Paolo , Nerjaku Fitnete , Finotto Silvia , Cattelan Annamaria , Calabrò Maria Luisa , Belloni Fortina Anna , Russano Francesco , Mazza Marcodomenico , Galuppo Sara , Bezzon Elisabetta , Sbaraglia Marta , Krengli Marco , Brunello Antonella , Mocellin Simone , Piaserico Stefano , Alaibac Mauro
Published: February 2024

Kaposi’s sarcoma (KS) is a rare angioproliferative tumor classified in four different clinical–epidemiological forms. The diagnosis is based on histopathological and immunohistochemical analyses. The treatment is heterogeneous and includes several local and systemic therapeutic strategies. Methods: This is a retrospective cohort study including 86 KS patients treated between 1993 and 2022 at the University Hospital of Padua (AOPD) and at the Veneto Institute of Oncology (IOV). The data were extracted from an electronic database. Survival curves were generated using the Kaplan–Meier method, and Cox regression models were employed to explore associations with overall and disease-free survival. The male sex (89.53%), classical variant (43.02%), and cutaneous involvement (77.9%) were predominant. More than 61.6% of patients received a single treatment. Surgery, antiretroviral therapy, and chemotherapy were the mostly adopted approaches. A persistent response was observed in approximately 65% of patients, with a 22% relapse rate (at least 2 years). The overall survival ranges from 90 to 70% at 2 to 10 years after the diagnosis. Iatrogenic KS demonstrated a higher mortality (52.9%). This study reflects our experience in the management of KS. Comorbidities are very frequent, and treatments are heterogeneous. A multidisciplinary approach involving multiple referral specialists is essential for the appropriate management of this disease during diagnosis, treatment, and follow-up.
Recent Modification Strategies of MoS2 towards Electrocatalytic Hydrogen Evolution
Authors: Liu Lei , Liu Ning , Chen Biaohua , Dai Chengna , Wang Ning
Published: February 2024

Hydrogen production by the electrolysis of water is a green and efficient method, which is of great significance for achieving sustainable development. Molybdenum disulfide (MoS2) is a promising electrocatalyst for hydrogen evolution reaction (HER) due to its high electrochemical activity, low cost, and abundant reserves. In comparison to the noble metal Pt, MoS2 has poorer hydrogen evolution performance in water electrolysis. Therefore, further modifications of MoS2 need to be developed aiming at improving its catalytic performance. The present work summarizes the modification strategies that have been developed in the past three years on hydrogen evolution from water electrolysis by utilizing MoS2 as the electrocatalyst and following the two aspects of internal and external modifications. The former includes the strategies of interlayer spacing, sulfur vacancy, phase transition, and element doping, while the latter includes the heterostructure and conductive substrate. If the current gap in this paper’s focus on modification strategies for electrocatalytic hydrogen evolution in water electrolysis is addressed, MoS2 will perform best in acidic or alkaline media. In addition to that, the present work also discusses the challenges and future development directions of MoS2 catalysts.
Brain-Type Glycogen Phosphorylase (PYGB) in the Pathologies of Diseases: A Systematic Review
Authors: Yang Caiting , Wang Haojun , Shao Miaomiao , Chu Fengyu , He Yuyu , Chen Xiaoli , Fan Jiahui , Chen Jingwen , Cai Qianqian , Wu Changxin
Published: February 2024

Glycogen metabolism is a form of crucial metabolic reprogramming in cells. PYGB, the brain-type glycogen phosphorylase (GP), serves as the rate-limiting enzyme of glycogen catabolism. Evidence is mounting for the association of PYGB with diverse human diseases. This review covers the advancements in PYGB research across a range of diseases, including cancer, cardiovascular diseases, metabolic diseases, nervous system diseases, and other diseases, providing a succinct overview of how PYGB functions as a critical factor in both physiological and pathological processes. We present the latest progress in PYGB in the diagnosis and treatment of various diseases and discuss the current limitations and future prospects of this novel and promising target.
E3 Ligases Regulate Organelle Inheritance in Yeast
Authors: Obara Keisuke , Nishimura Kohei , Kamura Takumi
Published: February 2024

Saccharomyces cerevisiae proliferates by budding, which includes the formation of a cytoplasmic protrusion called the ‘bud’, into which DNA, RNA, proteins, organelles, and other materials are transported. The transport of organelles into the growing bud must be strictly regulated for the proper inheritance of organelles by daughter cells. In yeast, the RING-type E3 ubiquitin ligases, Dma1 and Dma2, are involved in the proper inheritance of mitochondria, vacuoles, and presumably peroxisomes. These organelles are transported along actin filaments toward the tip of the growing bud by the myosin motor protein, Myo2. During organelle transport, organelle-specific adaptor proteins, namely Mmr1, Vac17, and Inp2 for mitochondria, vacuoles, and peroxisomes, respectively, bridge the organelles and myosin. After reaching the bud, the adaptor proteins are ubiquitinated by the E3 ubiquitin ligases and degraded by the proteasome. Targeted degradation of the adaptor proteins is necessary to unload vacuoles, mitochondria, and peroxisomes from the actin–myosin machinery. Impairment of the ubiquitination of adaptor proteins results in the failure of organelle release from myosin, which, in turn, leads to abnormal dynamics, morphology, and function of the inherited organelles, indicating the significance of proper organelle unloading from myosin. Herein, we summarize the role and regulation of E3 ubiquitin ligases during organelle inheritance in yeast.
Differential Role of the RAC1-Binding Proteins FAM49b (CYRI-B) and CYFIP1 in Platelets
Authors: Sisario Dmitri , Spindler Markus , Ermer Katharina J. , Grütz Noah , Nicolai Leo , Gaertner Florian , Machesky Laura M. , Bender Markus
Published: February 2024

Platelet function at vascular injury sites is tightly regulated through the actin cytoskeleton. The Wiskott–Aldrich syndrome protein-family verprolin-homologous protein (WAVE)-regulatory complex (WRC) activates lamellipodia formation via ARP2/3, initiated by GTP-bound RAC1 interacting with the WRC subunit CYFIP1. The protein FAM49b (Family of Unknown Function 49b), also known as CYRI-B (CYFIP-Related RAC Interactor B), has been found to interact with activated RAC1, leading to the negative regulation of the WRC in mammalian cells. To investigate the role of FAM49b in platelet function, we studied platelet-specific Fam49b−/−-, Cyfip1−/−-, and Cyfip1/Fam49b−/−-mice. Platelet counts and activation of Fam49b−/− mice were comparable to those of control mice. On fully fibrinogen-coated surfaces, Fam49b−/−-platelets spread faster with an increased mean projected cell area than control platelets, whereas Cyfip1/Fam49b−/−-platelets did not form lamellipodia, phenocopying the Cyfip1−/−-platelets. However, Fam49b−/−-platelets often assumed a polarized shape and were more prone to migrate on fibrinogen-coated surfaces. On 2D structured micropatterns, however, Fam49b−/−-platelets displayed reduced spreading, whereas spreading of Cyfip1−/−- and Cyfip1/Fam49b−/−-platelets was enhanced. In summary, FAM49b contributes to the regulation of morphology and migration of spread platelets, but to exert its inhibitory effect on actin polymerization, the functional WAVE complex must be present.