bluuebunny/crossref_metadata_2025 huggingface dataset:
A Systematic Review of Structural and Functional MRI Studies Investigating Social Networking Site Use
Authors: Wadsley Michael , Ihssen Niklas
Published: May 2023

An understanding of the neurocognitive profile underlying the use of social networking sites (SNSs) can help inform decisions about the classification of problematic SNS use as an addictive disorder and elucidate how/when ‘SNS addiction’ might develop. The present review aimed to synthesize structural and functional MRI research investigating problematic/compulsive forms of SNS use or regular (non-addicted) SNS use behaviours. We conducted a systematic search for research articles published in English using the Web of Science, PubMed, and Scopus databases up to October 2022. Studies meeting our inclusion criteria were assessed for quality and a narrative synthesis of the results was conducted. Twenty-eight relevant articles were identified comprising structural MRI (n = 9), resting-state fMRI (n = 6) and task-based fMRI studies (n = 13). Current evidence suggests that problematic SNS use might be characterised by (1) reduced volume of the ventral striatum, amygdala, subgenual anterior cingulate cortex, orbitofrontal cortex and posterior insula; (2) increased ventral striatum and precuneus activity in response to SNS cues; (3) abnormal functional connectivity involving the dorsal attention network; (4) inter-hemispheric communication deficits. Regular SNS use behaviours appear to recruit regions involved in the mentalising network, the self-referential cognition network, the salience network, the reward network and the default mode network. Such findings are at least partially consistent with observations from the substance addiction literature and provide some provisional support for the addictive potential of SNSs. Nonetheless, the present review is limited by the small number of eligible studies and large heterogeneity in the methods employed, and so our conclusions should remain tentative. Moreover, there is a lack of longitudinal evidence suggesting SNSs cause neuroadaptations and thus conclusions that problematic SNS use represents a disease process akin to substance use addictions are premature. More well-powered longitudinal research is needed to establish the neural consequences of excessive and problematic SNS use.
The Dynamic Interplay between Loss of Semantic Memory and Semantic Learning Capacity: Insight from Neologisms Learning in Semantic Variant Primary Progressive Aphasia
Authors: Luzzi Simona , Baldinelli Sara , Fiori Chiara , Morelli Mauro , Gainotti Guido
Published: May 2023

Semantic Variant of Primary Progressive Aphasia (svPPA) has often been considered as a loss of knowledge stored in semantic memory, but might also be due to a general disruption of mechanisms allowing the acquisition, storage, and retrieval of semantic memories. In order to assess any parallelism in svPPA patients between loss of semantic knowledge and inability to acquire new semantic information, we administered a battery of semantic learning tasks to healthy individuals and svPPA patients, where they were requested to learn new conceptual representations and new word forms, and to associate the former with the latter. A strong relation was found between loss of semantic knowledge and disruption of semantic learning: (a) patients with severe svPPA had the lowest scores in the semantic learning tasks; (b) significant correlations were found between scores obtained in semantic learning tasks and scores obtained in semantic memory disorders in svPPA patients.
Trimethylamine N-Oxide Exacerbates Neuroinflammation and Motor Dysfunction in an Acute MPTP Mice Model of Parkinson’s Disease
Authors: Quan Wei , Qiao Chen-Meng , Niu Gu-Yu , Wu Jian , Zhao Li-Ping , Cui Chun , Zhao Wei-Jiang , Shen Yan-Qin
Published: May 2023

Observational studies have shown abnormal changes in trimethylamine N-oxide (TMAO) levels in the peripheral circulatory system of Parkinson’s disease (PD) patients. TMAO is a gut microbiota metabolite that can cross the blood–brain barrier and is strongly related to neuroinflammation. Neuroinflammation is one of the pathological drivers of PD. Herein, we investigated the effect of TMAO on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model mice. TMAO pretreatment was given by adding 1.5% (w/v) TMAO to the drinking water of the mice for 21 days; then, the mice were administered MPTP (20 mg/kg, i.p.) four times a day to construct an acute PD model. Their serum TMAO concentrations, motor function, dopaminergic network integrity, and neuroinflammation were then assayed. The results showed that TMAO partly aggravated the motor dysfunction of the PD mice. Although TMAO had no effect on the dopaminergic neurons, TH protein content, and striatal DA level in the PD mice, it significantly reduced the striatal 5-HT levels and aggravated the metabolism of DA and 5-HT. Meanwhile, TMAO significantly activated glial cells in the striatum and the hippocampi of the PD mice and promoted the release of inflammatory cytokines in the hippocampus. In summary, higher-circulating TMAO had adverse effects on the motor capacity, striatum neurotransmitters, and striatal and hippocampal neuroinflammation in PD mice.
Maintained Spatial Learning and Memory Functions in Middle-Aged α9 Nicotinic Receptor Subunit Knock-Out Mice
Authors: Vicencio-Jimenez Sergio , Delano Paul H. , Madrid Natalia , Terreros Gonzalo , Maass Juan C. , Delgado Carolina , Jorratt Pascal
Published: May 2023

Age-related hearing loss is linked to cognitive impairment, but the mechanisms that relate to these conditions remain unclear. Evidence shows that the activation of medial olivocochlear (MOC) neurons delays cochlear aging and hearing loss. Consequently, the loss of MOC function may be related to cognitive impairment. The α9/α10 nicotinic receptor is the main target of cholinergic synapses between the MOC neurons and cochlear outer hair cells. Here, we explored spatial learning and memory performance in middle-aged wild-type (WT) and α9-nAChR subunit knock-out (KO) mice using the Barnes maze and measured auditory brainstem response (ABR) thresholds and the number of cochlear hair cells as a proxy of cochlear aging. Our results show non-significant spatial learning differences between WT and KO mice, but KO mice had a trend of increased latency to enter the escape box and freezing time. To test a possible reactivity to the escape box, we evaluated the novelty-induced behavior using an open field and found a tendency towards more freezing time in KO mice. There were no differences in memory, ABR threshold, or the number of cochlear hair cells. We suggest that the lack of α9-nAChR subunit alters novelty-induced behavior, but not spatial learning in middle-aged mice, by a non-cochlear mechanism.
Comparing Older Parents’ and Adult Children’s Fear of Falling and Perceptions of Age-Friendly Home Modification: An Integration of the Theories of Planned Behavior and Protection Motivation
Authors: Kwon Hyun Joo , Oh Jiyoung
Published: May 2023

This study investigated how a fear of falling affects perceptions and behavioral intentions toward age-friendly home modification (AFHM) in older parents and adult children by integrating the theory of planned behavior (TPB) to explain AFHM decision-making processes and the protection motivation theory to explain the impact of a fear of falling on AFHM intention. The target population comprised older parents (≥75 years old) and adult children (45–64 years old) in Busan, South Korea (N = 600). The participants completed a self-administered questionnaire in March 2022. Independent t-test and path model analyses were conducted to compare primary constructs between older parents and adult children and analyze the relationships among a fear of falling, TPB components, and AFHM intention. Results showed that both groups had positive attitudes toward AFHM. However, adult children showed significantly higher rates of having a fear of falling, lower perceived behavioral control, and higher AFHM intention than older parents. The proposed research models were partially supported in the older-parent group and fully supported in the adult-children group. Adult children play a critical role in AFHM, along with older adults who are directly involved in an aging society. AFHM-supporting programs, including monetary and human-force assistance, education, related public advertisements, and an active AFHM market, should be expanded.
Personality Characteristics of Children and Adolescents with Anxiety Disorder from a Maternal Perspective: A Brief Report
Authors: Santos Erica da Cruz , Lopes Maria-Cecilia , Asbahr Fernando Ramos , Rodrigues Camila Luisi , Saffi Fabiana , Spruyt Karen , Serafim Antonio de Padua , Rocca Cristiana Castanho de Almeida
Published: May 2023

The present study assessed the personality characteristics of children and adolescents with anxiety disorder from a maternal perspective. A total of 48 children and adolescents aged between 8 and 17 years participated in this study, which was organized as follows: a clinical group (24 children and adolescents with anxiety disorders and their respective mothers) and a control group (24 children and adolescents without psychiatric diagnosis and their mothers). The participants were submitted to the WASI, CBCL, MASC-2, and EPQ-J tests and their mothers to the SRQ-20 and PIC-2 tests. The results showed higher rates of internalizing symptoms in the clinical group. In addition, patients showed less interest in hobbies, less adherence to social organizations, impairment in social activities, and commitment to school performance compared to the control group. There was a positive correlation between the mothers’ symptoms and each of the following PIC-2 domains: somatic concern (p < 0.01) and psychological discomfort (p < 0.01). In conclusion, youths with AD showed a withdrawn and reserved personality profile, involving distrust of impulses and avoidance of interactions with peers. Furthermore, psychoemotional problems of mothers adversely influenced the perception followed by anxiety and adjustment characteristics. More studies are needed to assess the maternal personality in youths with anxiety.
L-Moments-Based FORM Method for Structural Reliability Analysis Considering Correlated Input Random Variables
Authors: Li Zhi-Peng , Hu Dong-Zhu , Zhang Long-Wen , Zhang Zhen , Shi Yue
Published: May 2023

Leveraging the properties of the first three linear moments (L-moments), this study proposes an effective normal transformation for structural reliability analysis considering correlated input random variables, in which the admissible range of the initial correlation matrix when employing this transformation is also presented. Subsequently, a practical procedure for structural reliability analysis, grounded in the proposed transformation and first-order reliability method (FROM), is proposed, accommodating instances wherein the joint probability density functions (PDFs) or marginal PDFs of the relevant random variables remain unknown. In comparison to the technique premised on the first three central moments (C-moments), the proposed method, based on the first three L-moments, exhibits a more extensive applicability. Various practical scenarios showcase the method’s effectiveness and precision in calculating the structural reliability index, considering diverse distributions, numerous variables, and complex structures.
Enhancing Public Engagement in Architectural Design: A Comparative Analysis of Advanced Virtual Reality Approaches in Building Information Modeling and Gamification Techniques
Authors: Ehab Ahmed , Burnett Gary , Heath Tim
Published: May 2023

Purpose: This paper investigates the potential of virtual reality (VR) technologies—specifically, building information modeling (BIM) (“Autodesk Revit”) and game engines (“Unreal Engine”)—to enhance public involvement in the design and execution of architecture and urban projects. The main research question focuses on comparing the effectiveness of these two methods in creating an interactive design model for participatory design in public spaces. Methods: The study employed a VR exploratory experiment with 33 participants, followed by semi-structured interviews to analyze two recent developments in London: the Sky Garden, and Crossrail Place Roof Garden. Participants interacted with the design models and provided feedback on their experiences. Results: The findings demonstrate that integrating VR with BIM software using the Enscape plugin effectively enhances user involvement, enabling real-time generation and testing of design alternatives. While both methods were found to be beneficial, participants reported a preference for the direct implementation of VR in BIM software. Conclusions: This research highlights the potential of VR technologies—specifically, BIM and game engines—as a co-design approach for public and social spaces in urban environments. It also identifies limitations and future research opportunities in adopting these methods for participatory design.
18F-FDG PET-Derived Volume-Based Parameters to Predict Disease-Free Survival in Patients with Grade III Breast Cancer of Different Molecular Subtypes Candidates to Neoadjuvant Chemotherapy
Authors: Quartuccio Natale , Alongi Pierpaolo , Urso Luca , Ortolan Naima , Borgia Francesca , Bartolomei Mirco , Arnone Gaspare , Evangelista Laura
Published: May 2023

We investigated whether baseline [18F] Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)-derived semiquantitative parameters could predict disease-free survival (DFS) in patients with grade III breast cancer (BC) of different molecular subtypes candidate to neoadjuvant chemotherapy (NAC). For each 18F-FDG-PET/CT scan, the following parameters were calculated in the primary tumor (SUVmax, SUVmean, MTV, TLG) and whole-body (WB_SUVmax, WB_MTV, and WB_TLG). Receiver operating characteristic (ROC) analysis was used to determine the capability to predict DFS and find the optimal threshold for each parameter. Ninety-five grade III breast cancer patients with different molecular types were retrieved from the databases of the University Hospital of Padua and the University Hospital of Ferrara (luminal A: 5; luminal B: 34; luminal B-HER2: 22; HER2-enriched: 7; triple-negative: 27). In luminal B patients, WB_MTV (AUC: 0.75; best cut-off: WB_MTV > 195.33; SS: 55.56%, SP: 100%; p = 0.002) and WB_TLG (AUC: 0.73; best cut-off: WB_TLG > 1066.21; SS: 55.56%, SP: 100%; p = 0.05) were the best predictors of DFS. In luminal B-HER2 patients, WB_SUVmax was the only predictor of DFS (AUC: 0.857; best cut-off: WB_SUVmax > 13.12; SS: 100%; SP: 71.43%; p < 0.001). No parameter significantly affected the prediction of DFS in patients with grade III triple-negative BC. Volume-based parameters, extracted from baseline 18F-FDG PET, seem promising in predicting recurrence in patients with grade III luminal B and luminal B- HER2 breast cancer undergoing NAC.
The Phosphorylation of Kv1.3: A Modulatory Mechanism for a Multifunctional Ion Channel
Authors: Navarro-Pérez María , Estadella Irene , Benavente-Garcia Anna , Orellana-Fernández Ruth , Petit Anna , Ferreres Joan Carles , Felipe Antonio
Published: May 2023

The voltage-gated potassium channel Kv1.3 plays a pivotal role in a myriad of biological processes, including cell proliferation, differentiation, and apoptosis. Kv1.3 undergoes fine-tuned regulation, and its altered expression or function correlates with tumorigenesis and cancer progression. Moreover, posttranslational modifications (PTMs), such as phosphorylation, have evolved as rapid switch-like moieties that tightly modulate channel activity. In addition, kinases are promising targets in anticancer therapies. The diverse serine/threonine and tyrosine kinases function on Kv1.3 and the effects of its phosphorylation vary depending on multiple factors. For instance, Kv1.3 regulatory subunits (KCNE4 and Kvβ) can be phosphorylated, increasing the complexity of channel modulation. Scaffold proteins allow the Kv1.3 channelosome and kinase to form protein complexes, thereby favoring the attachment of phosphate groups. This review compiles the network triggers and signaling pathways that culminate in Kv1.3 phosphorylation. Alterations to Kv1.3 expression and its phosphorylation are detailed, emphasizing the importance of this channel as an anticancer target. Overall, further research on Kv1.3 kinase-dependent effects should be addressed to develop effective antineoplastic drugs while minimizing side effects. This promising field encourages basic cancer research while inspiring new therapy development.
Anti-Tumor Strategies by Harnessing the Phagocytosis of Macrophages
Authors: Li Si-Yuan , Guo Yong-Lin , Tian Jia-Wen , Zhang He-Jing , Li Rui-Fang , Gong Ping , Yu Zi-Li
Published: May 2023

Macrophages are essential for the human body in both physiological and pathological conditions, engulfing undesirable substances and participating in several processes, such as organism growth, immune regulation, and maintenance of homeostasis. Macrophages play an important role in anti-bacterial and anti-tumoral responses. Aberrance in the phagocytosis of macrophages may lead to the development of several diseases, including tumors. Tumor cells can evade the phagocytosis of macrophages, and “educate” macrophages to become pro-tumoral, resulting in the reduced phagocytosis of macrophages. Hence, harnessing the phagocytosis of macrophages is an important approach to bolster the efficacy of anti-tumor treatment. In this review, we elucidated the underlying phagocytosis mechanisms, such as the equilibrium among phagocytic signals, receptors and their respective signaling pathways, macrophage activation, as well as mitochondrial fission. We also reviewed the recent progress in the area of application strategies on the basis of the phagocytosis mechanism, including strategies targeting the phagocytic signals, antibody-dependent cellular phagocytosis (ADCP), and macrophage activators. We also covered recent studies of Chimeric Antigen Receptor Macrophage (CAR-M)-based anti-tumor therapy. Furthermore, we summarized the shortcomings and future applications of each strategy and look into their prospects with the hope of providing future research directions for developing the application of macrophage phagocytosis-promoting therapy.
Beyond CTLA-4 and PD-1 Inhibition: Novel Immune Checkpoint Molecules for Melanoma Treatment
Authors: Ziogas Dimitrios C. , Theocharopoulos Charalampos , Lialios Panagiotis-Petros , Foteinou Dimitra , Koumprentziotis Ioannis-Alexios , Xynos Georgios , Gogas Helen
Published: May 2023

More than ten years after the approval of ipilimumab, immune checkpoint inhibitors (ICIs) against PD-1 and CTLA-4 have been established as the most effective treatment for locally advanced or metastatic melanoma, achieving durable responses either as monotherapies or in combinatorial regimens. However, a considerable proportion of patients do not respond or experience early relapse, due to multiple parameters that contribute to melanoma resistance. The expression of other immune checkpoints beyond the PD-1 and CTLA-4 molecules remains a major mechanism of immune evasion. The recent approval of anti-LAG-3 ICI, relatlimab, in combination with nivolumab for metastatic disease, has capitalized on the extensive research in the field and has highlighted the potential for further improvement of melanoma prognosis by synergistically blocking additional immune targets with new ICI-doublets, antibody–drug conjugates, or other novel modalities. Herein, we provide a comprehensive overview of presently published immune checkpoint molecules, including LAG-3, TIGIT, TIM-3, VISTA, IDO1/IDO2/TDO, CD27/CD70, CD39/73, HVEM/BTLA/CD160 and B7-H3. Beginning from their immunomodulatory properties as co-inhibitory or co-stimulatory receptors, we present all therapeutic modalities targeting these molecules that have been tested in melanoma treatment either in preclinical or clinical settings. Better understanding of the checkpoint-mediated crosstalk between melanoma and immune effector cells is essential for generating more effective strategies with augmented immune response.
PLA2R1 Inhibits Differentiated Thyroid Cancer Proliferation and Migration via the FN1-Mediated ITGB1/FAK Axis
Authors: Zheng Hui , Zhang Mengyu , Gao Dingwei , Zhang Xiaoying , Cai Haidong , Cui Zhijun , Gao Yang , Lv Zhongwei
Published: May 2023

PLA2R1 is a novel gene that is aberrantly expressed in a variety of malignancies. However, the role and mechanism of PLA2R1 in thyroid cancer has not been elucidated. We aimed to uncover the underlying mechanism of PLA2R1 in thyroid cancer. We collected 115 clinical specimens, including 54 tumor tissues and 61 para-cancerous tissues, who underwent surgical treatment at Shanghai Tenth Hospital. Immunohistochemical staining was used to evaluate PLA2R1 expression in differentiated thyroid cancer (DTC) tissues. The thyroid cancer cell lines 8505c and FTC133 transfected with PLA2R1 overexpression or knockdown plasmids were used for CCK8 assays and a wound healing assay. Next, we conducted coimmunoprecipitation (Co-IP) experiments and western blotting to explore the underlying mechanism of PLA2R1 in regulating the growth of thyroid cancer. We discovered that the expression of PLA2R1 was lower in the tumor tissues than in para-cancerous tissues (χ2 = 37.0, p < 0.01). The overexpression of PLA2R1 significantly suppressed thyroid cancer cell proliferation and migration, and both of these effects were partially attenuated by the knockdown of PLA2R1. Furthermore, the in vivo growth of DTC could be alleviated by the knockdown of PLA2R1. The mechanistic study revealed that PLA2R1 competed with FN1 for binding to ITGB1, inhibiting the FAK axis and epithelial-mesenchymal transition (EMT). We speculate that PLA2R1 might be a promising marker and a novel therapeutic target for thyroid cancer.
Recent Advances in Molecular Mechanisms of Cancer Immunotherapy
Authors: Kciuk Mateusz , Yahya Esam Bashir , Mohamed Ibrahim Mohamed Montaha , Rashid Summya , Iqbal Muhammad Omer , Kontek Renata , Abdulsamad Muhanad A. , Allaq Abdulmutalib A.
Published: May 2023

Cancer is among the current leading causes of death worldwide, despite the novel advances that have been made toward its treatment, it is still considered a major public health concern. Considering both the serious impact of cancer on public health and the significant side effects and complications of conventional therapeutic options, the current strategies towards targeted cancer therapy must be enhanced to avoid undesired toxicity. Cancer immunotherapy has become preferable among researchers in recent years compared to conventional therapeutic options, such as chemotherapy, surgery, and radiotherapy. The understanding of how to control immune checkpoints, develop therapeutic cancer vaccines, genetically modify immune cells as well as enhance the activation of antitumor immune response led to the development of novel cancer treatments. In this review, we address recent advances in cancer immunotherapy molecular mechanisms. Different immunotherapeutic approaches are critically discussed, focusing on the challenges, potential risks, and prospects involving their use.
GNL3 and PA2G4 as Prognostic Biomarkers in Prostate Cancer
Authors: Kumar Shashank , Shuaib Mohd , AlAsmari Abdullah F. , Alqahtani Faleh , Gupta Sanjay
Published: May 2023

Prostate cancer is a multifocal and heterogeneous disease common in males and remains the fifth leading cause of cancer-related deaths worldwide. The prognosis of prostate cancer is variable and based on the degree of cancer and its stage at the time of diagnosis. Existing biomarkers for the prognosis of prostate cancer are unreliable and lacks specificity and sensitivity in guiding clinical decision. There is need to search for novel biomarkers having prognostic and predictive capabilities in guiding clinical outcomes. Using a bioinformatics approach, we predicted GNL3 and PA2G4 as biomarkers of prognostic significance in prostate cancer. A progressive increase in the expression of GNL3 and PA2G4 was observed during cancer progression having significant association with poor survival in prostate cancer patients. The Receiver Operating Characteristics of both genes showed improved area under the curve against sensitivity versus specificity in the pooled samples from three different GSE datasets. Overall, our analysis predicted GNL3 and PA2G4 as prognostic biomarkers of clinical significance in prostate cancer.
Biosynthetic Mesh Reconstruction after Abdominoperineal Resection for Low Rectal Cancer: Cross Relation of Surgical Healing and Oncological Outcomes: A Multicentric Observational Study
Authors: Gambardella Claudio , Mongardini Federico Maria , Karpathiotakis Menelaos , Lucido Francesco Saverio , Pizza Francesco , Tolone Salvatore , Parisi Simona , Nesta Giusiana , Brusciano Luigi , Gambardella Antonio , Docimo Ludovico , Mongardini Massimo
Published: May 2023

Background: Local wound complications are among the most relevant sequelae after an abdominoperineal resection (APR) for low rectal cancer. One of the proposed techniques to improve the postoperative recovery and to accelerate the initiation of adjuvant chemotherapy is the mesh reinforcement of the perineal wound. The aim of the current study is to compare the surgical and oncological outcomes after APR performed with a biosynthetic mesh reconstruction versus the conventional procedure. Methods: From 2015 to 2020, in two tertiary centres, the surgical outcomes, the wound events (i.e., surgical site infections, wound dehiscence and the complete healing time) and the oncological outcomes (i.e., time length to start adjuvant chemo-radiotherapy, an over 8-week delay in chemotherapy and the recurrence rate) were retrospectively analysed in patients undergoing APR reinforced with biosynthetic mesh (Group A) and conventional APR (Group B). Results Sixty-one patients were treated with APR (25 in Group A and 36 in Group B). Patients in Group A presented lower time for: healing (16 versus 24 days, p = 0.015), inferior perineal wound dehiscence rates (one versus nine cases, p = 0.033), an earlier adjuvant therapy start (26 versus 70 days, p = 0.003) and a lower recurrence rate (16.6% vs. 33.3%, p = 0.152). Conclusions: In our series, the use of a biosynthetic mesh for the neo-perineum reconstruction after a Miles’ procedure has resulted in safe, reproducible results affected by limited complications, guarantying a rapid start of the adjuvant therapy with clear benefits in oncological outcomes. Further randomized clinical trials with long-term follow-up are needed to validate these results.
Salvage Radical Prostatectomy after Primary Focal Ablative Therapy: A Systematic Review and Meta-Analysis
Authors: Blank Fernando , Meyer Meredith , Wang Hannah , Abbas Hasan , Tayebi Shima , Hsu Wei-Wen , Sidana Abhinav
Published: May 2023

Context: Focal therapy (FT) has been gaining popularity as a treatment option for localized intermediate-risk prostate cancer (PCa) due to the associated lower morbidity compared to whole-gland treatment. However, there is an increased risk of local cancer recurrence requiring subsequent treatment in a small proportion of patients. Objective: To conduct a systematic review and meta-analysis to better describe and analyze patient postoperative, oncologic, and functional outcomes for those who underwent salvage radical prostatectomy (sRP) to manage their primary FT failure. Evidence acquisition: A systematic review was completed using three databases (PubMed, Embase, and CINAHL) from October to December 2021 to identify data on outcomes in patients who received sRP for cancer recurrence after prior focal treatment. Evidence synthesis: 12 articles (482 patients) were included. Median time to sRP was 24 months. Median follow-up time was 27 months. A meta-analysis revealed a postoperative complication rate of 15% (95% CI: 0.09, 0.24), with 4.6% meeting criteria for a major complication Clavien (CG) grade ≥3. Severe GU toxicity was seen in 3.6% of the patients, and no patients had severe GI toxicity. Positive surgical margins (PSM) were found in 27% (95% CI: 0.19, 0.37). Biochemical recurrence (BCR) after sRP occurred in 23% (95% CI: 0.17, 0.30), indicating a BCR-free probability of 77% at 2 years. Continence (pad-free) and potency (ability to have penetrative sex) were maintained in 67% (95% CI: 0.53, 0.78) and 37% (95% CI: 0.18, 0.62) at 12 months, respectively. Conclusion: Our evidence shows acceptable complication rates and oncologic outcomes; however, with suboptimal functional outcomes for patients undergoing sRP for recurrent PCa after prior FT. Inferior outcomes were observed for salvage treatment compared to primary radical prostatectomy (pRP). More high-quality studies are needed to better characterize outcomes after this sequence of PCa treatments. Patient summary: We looked at treatment outcomes and toxicity for men treated with sRP for prior FT failure. We conclude that these patients will have significant detriment to genitourinary function, with outcomes being worse than those for pRP patients.
Decoding Immune Signature to Detect the Risk for Early-Stage HCC Recurrence
Authors: Devan Aswathy R. , Nair Bhagyalakshmi , Aryan Manu Kanjoormana , Liju Vijayastelar B. , Koshy Joel Joy , Mathew Bijo , Valsan Arun , Kim Hoon , Nath Lekshmi R.
Published: May 2023

Hepatocellular carcinoma (HCC) is often recognized as an inflammation-linked cancer, which possesses an immunosuppressive tumor microenvironment. Curative treatments such as surgical resection, liver transplantation, and percutaneous ablation are mainly applicable in the early stage and demonstrate significant improvement of survival rate in most patients. However, 70–80% of patients report HCC recurrence within 5 years of curative treatment, representing an important clinical issue. However, there is no effective recurrence marker after surgical and locoregional therapies, thus, tumor size, number, and histological features such as cancer cell differentiation are often considered as risk factors for HCC recurrence. Host immunity plays a critical role in regulating carcinogenesis, and the immune microenvironment characterized by its composition, functional status, and density undergoes significant alterations in each stage of cancer progression. Recent studies reported that analysis of immune contexture could yield valuable information regarding the treatment response, prognosis and recurrence. This review emphasizes the prognostic value of tumors associated with immune factors in HCC recurrence after curative treatment. In particular, we review the immune landscape and immunological factors contributing to early-stage HCC recurrence, and discuss the immunotherapeutic interventions to prevent tumor recurrence following curative treatments.
Preclinical Validation of an Advanced Therapy Medicinal Product Based on Cytotoxic T Lymphocytes Specific for Mutated Nucleophosmin (NPM1mut) for the Treatment of NPM1mut-Acute Myeloid Leukemia
Authors: De Cicco Marica , Lagreca Ivana , Basso Sabrina , Barozzi Patrizia , Muscianisi Stella , Bianco Alba , Riva Giovanni , Di Vincenzo Sara , Pulvirenti Chiara , Sapuppo Davide , Siciliano Mariangela , Rosti Vittorio , Candoni Anna , Zecca Marco , Forghieri Fabio , Luppi Mario , Comoli Patrizia
Published: May 2023

Acute myeloid leukemia (AML) with nucleophosmin (NPM1) genetic mutations is the most common subtype in adult patients. Refractory or relapsed disease in unfit patients or after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has a poor prognosis. NPM1-mutated protein, stably expressed on tumor cells but not on normal tissues, may serve as an ideal target for NPM1-mutated AML immunotherapy. The study aim was to investigate the feasibility of producing mutated-NPM1-specific cytotoxic T cells (CTLs) suitable for somatic cell therapy to prevent or treat hematologic relapse in patients with NPM1-mutated AML. T cells were expanded or primed from patient or donor peripheral blood mononuclear cells by NPM1-mutated protein-derived peptides, and tested for leukemia antigen-targeted cytotoxic activity, cytokine production and hematopoietic precursor inhibitory effect. We found that mutated-NPM1-specific CTLs, displaying specific cytokine production and high-level cytotoxicity against patients’ leukemia blasts, and limited inhibitory activity in clonogenic assays, could be obtained from both patients and donors. The polyfunctional mutated-NPM1-specific CTLs included both CD8+ and CD4+ T cells endowed with strong lytic capacity. Our results suggest that mutated-NPM1-targeted CTLs may be a useful therapeutic option to control low-tumor burden relapse following conventional chemotherapy in older NPM1-mutated AML patients or eradicate persistent MRD after HSCT.
The Sentinel Lymph Node in Treatment Planning: A Narrative Review of Lymph-Flow-Guided Radiotherapy
Authors: Ah-Thiane Loic , Rousseau Caroline , Aumont Maud , Cailleteau Axel , Doré Mélanie , Mervoyer Augustin , Vaugier Loig , Supiot Stéphane
Published: May 2023

The sentinel lymph node technique is minimally invasive and used routinely by surgeons, reducing the need for morbid extensive lymph node dissections, which is a significant advantage for cancer staging and treatment decisions. The sentinel lymph node could also help radiation oncologists to identify tumor drainage for each of their patients, leading to a more personalized radiotherapy, instead of a probabilistic irradiation based on delineation atlases. The aim is both to avoid recurrence in unexpected areas and to limit the volume of irradiated healthy tissues. The aim of our study is to evaluate the impact of sentinel lymph node mapping for radiation oncologists. This concept, relying on sentinel lymph node mapping for treatment planning, is known as lymph-flow-guided radiotherapy. We present an up-to-date narrative literature review showing the potential applications of the sentinel lymph node technique for radiotherapy, as well as the limits that need to be addressed before its routine usage.
Biosynthesis of Furfurylamines in Batch and Continuous Flow by Immobilized Amine Transaminases
Authors: Heinks Tobias , Merz Luisa M. , Liedtke Jan , Höhne Matthias , van Langen Luuk M. , Bornscheuer Uwe T. , Fischer von Mollard Gabriele , Berglund Per
Published: May 2023

Building blocks with amine functionality are crucial in the chemical industry. Biocatalytic syntheses and chemicals derived from renewable resources are increasingly desired to achieve sustainable production of these amines. As a result, renewable materials such as furfurals, especially furfurylamines like 5-(hydroxymethyl)furfurylamine (HMFA) and 2,5-di(aminomethyl)furan (DAF), are gaining increasing attention. In this study, we identified four different amine transaminases (ATAs) that catalyze the reductive amination of 5-(hydroxymethyl)furfural (HMF) and 2,5-diformylfuran (DFF). We successfully immobilized these ATAs on glutaraldehyde-functionalized amine beads using multiple binding and on amine beads by site-selective binding of the unique Cα-formylglycine within an aldehyde tag. All immobilized ATAs were efficiently reused in five repetitive cycles of reductive amination of HMF with alanine as co-substrate, while the ATA from Silicibacter pomeroyi (ATA-Spo) also exhibited high stability for reuse when isopropylamine was used as an amine donor. Additionally, immobilized ATA-Spo yielded high conversion in the batch syntheses of HMFA and DAF using alanine (87% and 87%, respectively) or isopropylamine (99% and 98%, respectively) as amine donors. We further demonstrated that ATA-Spo was effective for the reductive amination of HMF with alanine or isopropylamine in continuous-flow catalysis with high conversion up to 12 days (48% and 41%, respectively).
Ion Channels as Potential Tools for the Diagnosis, Prognosis, and Treatment of HPV-Associated Cancers
Authors: Chiliquinga Andrea Jazmín , Acosta Brenda , Ogonaga-Borja Ingrid , Villarruel-Melquiades Fernanda , de la Garza Jaime , Gariglio Patricio , Ocádiz-Delgado Rodolfo , Ramírez Ana , Sánchez-Pérez Yesennia , García-Cuellar Claudia M. , Bañuelos Cecilia , Camacho Javier
Published: May 2023

The human papilloma virus (HPV) group comprises approximately 200 genetic types that have a special affinity for epithelial tissues and can vary from producing benign symptoms to developing into complicated pathologies, such as cancer. The HPV replicative cycle affects various cellular and molecular processes, including DNA insertions and methylation and relevant pathways related to pRb and p53, as well as ion channel expression or function. Ion channels are responsible for the flow of ions across cell membranes and play very important roles in human physiology, including the regulation of ion homeostasis, electrical excitability, and cell signaling. However, when ion channel function or expression is altered, the channels can trigger a wide range of channelopathies, including cancer. In consequence, the up- or down-regulation of ion channels in cancer makes them attractive molecular markers for the diagnosis, prognosis, and treatment of the disease. Interestingly, the activity or expression of several ion channels is dysregulated in HPV-associated cancers. Here, we review the status of ion channels and their regulation in HPV-associated cancers and discuss the potential molecular mechanisms involved. Understanding the dynamics of ion channels in these cancers should help to improve early diagnosis, prognosis, and treatment in the benefit of HPV-associated cancer patients.
Effect of the Infill Patterns on the Mechanical and Surface Characteristics of 3D Printing of PLA, PLA+ and PETG Materials
Authors: Kadhum A. H. , Al-Zubaidi Salah , Abdulkareem Salah S.
Published: May 2023

This study aims to evaluate the 3D-printed parts of different materials in terms of the achieved mechanical properties and surface characteristics. Fourteen infill patterns were employed in the 3D printing of polylactic acid (PLA), enhanced polylactic acid (PLA+), and polyethylene terephthalate glycol (PETG) materials. The printed specimens’ mechanical properties and surface characteristics were evaluated and discussed. Ultimate tensile strengths, Young’s modulus, and strain at break % were determined as mechanical properties, while average, maximum, and total height of profiles (Ra, Rz, and Rt) were measured as surface characteristics of the produced specimens. The cubic, gyroid, and concentric patterns were found to be the best infill patterns in terms of the mechanical properties of PLA, PLA+, and PETG materials, where maximum ultimate tensile strengths were recorded for these materials: 15.6250, 20.8333, and 16.5483 MPa, respectively. From the other side, the best Ra, Rz, and Rt were achieved with cross, quarter cubic, and concentric patterns of the PLA, PETG, and PLA+ materials, where the best values were (2.832 µm, 8.19 µm, and 17.53), (4.759 µm, 24.113 µm, and 35.216), and (4.234 µm, 30.136 µm, and 31.896), respectively.
Selective Fluorimetric Detection of Pyrimidine Nucleotides in Neutral Aqueous Solution with a Styrylpyridine-Based Cyclophane
Authors: Schlosser Julika , Hebborn Julian F. M. , Berdnikova Daria V. , Ihmels Heiko
Published: May 2023

A styrylpyridine-containing cyclophane with diethylenetriamine linkers is presented as a host system whose association with representative nucleotides was examined with photometric and fluorimetric titrations. The spectrometric titrations revealed the formation of 1:1 complexes with log Kb values in the range of 2.3–3.2 for pyrimidine nucleotides TMP (thymidine monophosphate), TTP (thymidine triphosphate) and CMP (cytidine monophosphate) and 3.8–5.0 for purine nucleotides AMP (adenosine monophosphate), ATP (adenosine triphosphate), and dGMP (deoxyguanosine monophosphate). Notably, in a neutral buffer solution, the fluorimetric response to the complex formation depends on the type of nucleotide. Hence, quenching of the already weak fluorescence was observed with the purine bases, whereas the association of the cyclophane with pyrimidine bases TMP, TTP, and CMP resulted in a significant fluorescence light-up effect. Thus, it was demonstrated that the styrylpyridine unit is a useful and complementary fluorophore for the development of selective nucleotide-targeting fluorescent probes based on alkylamine-linked cyclophanes.
Short I⋯O Interactions in the Crystal Structures of Two 2-Iodo-Phenyl Methyl-Amides as Substrates for Radical Translocation Reactions
Authors: Ishaq Ahtsham , Storey John M. D. , Harrison William T. A.
Published: May 2023

Radical translocation reactions are finding various uses in organic synthesis, in particular the stereospecific formation of complex natural products. In this work, the syntheses and single-crystal structures of two substituted 2-iodo-phenyl methyl-amides are reported, namely cyclo-propane carboxylic acid (2-iodo-phenyl)-methyl-amide, C11H12INO (1), and cyclo-heptane carboxylic acid (2-iodo-phenyl)-methyl-amide, C15H20INO (2). In each case, the methyl-amide group has a syn conformation, and this grouping is perpendicular to the plane of the benzene ring: these solid-state conformations appear to be well setup to allow an intramolecular hydrogen atom transfer to take place as part of a radical translocation reaction. Short intermolecular I⋯O halogen bonds occur in each crystal structure, leading to [010] chains in 1 [I⋯O = 3.012 (2) Å] and isolated dimers in 2 [I⋯O = 3.024 (4) and 3.057 (4) Å]. The intermolecular interactions are further quantified by Hirshfeld surface analyses.
Preparation of 2-Butanone Gas Sensor Based on Ag-Decorated In2O3 Nanocube with High Response and Low Detection Level
Authors: Zhang Hua , Guo Yinghao , Gao Hongliang , Meng Fanli
Published: May 2023

In this work, 2-butanone-sensitive Ag-decorated In2O3 nanocomposites were successfully prepared using a facile one-step hydrothermal method to enhance the sensing performance of In2O3 nanocubes. The methods of scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD), energy dispersive spectroscopy (EDS) analysis, and X-ray photoelectron spectroscopy (XPS) were used to observe the morphology, microstructure, crystalline phase, and the existing state of the elements in the produced nanomaterials, respectively. The gas sensing test results show that the prepared compounds could respond to 100 ppm of 2-butanone with a high response (242), fourfold that of the pure In2O3 material, at the optimum working temperature of 240 °C. Moreover, the Ag@In2O3-based sensor also showed excellent selectivity, good repeatability, and even long-term stability. In addition, noble metal surface modification not only decreased the optimum operating temperature (from 270 °C to 240 °C) but also decreased the lowest detection limit (from 5 ppm to 0.25 ppm). In the final section, the gas sensing mechanism of the Ag@In2O3-based sensor and the probable reason for 2-butanone’s enhanced sensing properties are both discussed.
Enzymeless Electrochemical Glucose Sensors Based on Metal–Organic Framework Materials: Current Developments and Progresses
Authors: Liu Chang , Zhou Jian , Yan Rongqiu , Wei Lina , Lei Chenghong
Published: May 2023

Electrochemical glucose sensors play a crucial role in medicine, bioscience, food science, and agricultural science. Metal–organic frameworks possess exceptional properties, such as large specific surface area, high porosity, tunable pore structure, high catalytic activity, open metal active sites, and structural diversity. The catalytic activity of metal–organic frameworks enables electrocatalytic oxidation of glucose without the need for enzymes. Consequently, enzymeless electrochemical glucose sensors based on metal–organic framework materials have gained much attention and have been extensively studied for glucose detection. This mini-review provides an overview of the development and progress of enzymeless electrochemical glucose detection based on metal–organic framework material–modified electrodes, including doping materials, sensitivity, detection limit, and fast response capability. With the advancement of this technology, enzymeless electrochemical glucose sensors can continuously and stably detect glucose and can be utilized in various fields, such as wearable devices.
Perinatal Characteristics and the Sensitization to Cow Milk, Egg Whites and Wheat in Children up to 3 Years of Age
Authors: Chang Hsin-Yu , Lee Zon-Min , Chang Ling-Sai , Feng Wei-Ling , Yang Yao-Hsu , Ou-Yang Mei-Chen
Published: May 2023

Food sensitization in early life identifies children at risk of developing allergic diseases. We investigated the sensitization to cow milk (CM), egg whites, and wheat. Newborns and infants under 3 years of age with available specific immunoglobulin E (sIgE) data were identified. A retrospective survey was conducted using data from the Chang Gung Research Database. Perinatal characteristics, such as singleton or multiples in a single pregnancy, parity, meconium staining, maternal age, spontaneous delivery or cesarean section, meconium passage, weeks of gestation, birth length, body weight, head and chest circumferences, and season, were obtained. The data on sIgE were collected, and a logistic regression model was used to determine the odds of sensitization. Positive sIgE for CM and egg whites was more likely to occur in boys than in girls. Early-life egg white and wheat sensitization was associated with increased birth body length and weight. A multivariate analysis indicated an association between egg white sIgE positivity and logarithmic total IgE. Higher total IgE levels and younger age were associated with egg white sensitization, and elevated weight and length at birth were linked to food sensitization, particularly to egg whites and wheat.
Psychological Well-Being, Self-Esteem, Quality of Life and Gender Differences as Determinants of Post-Traumatic Growth in Long-Term Knee Rotationplasty Survivors: A Cohort Study
Authors: Benedetti Maria Grazia , Tarricone Ilaria , Monti Manuela , Campanacci Laura , Regazzi Maria Giulia , De Matteis Tiziano , Platano Daniela , Manfrini Marco
Published: May 2023

Rotationplasty (RP) is a special surgical technique for bone tumors of the lower limb and is the chosen procedure for children under 6 with bone sarcoma in the distal femur. Leg reconstruction results in an unusual aspect of the limb potentially giving life-long emotional outcomes, especially considering the young age of most RP patients. Although the high level of the quality of life of these patients has been previously reported, aspects related to long-term psychological well-being, self-esteem and life satisfaction, particularly regarding the gender, procreation and parenting, have never been explored. The aim of this study was to assess the general degree of psychological well-being of RP patients, with specific reference to gender, procreation and parenting. Twenty long-term RP survivors of high-grade bone sarcoma participated in the study. They were administered the following validated questionnaires: HADS for psychological well-being (degree of anxiety and depression), Temperament and Character Inventory (TCI), RSES for self-esteem, SF-36 for quality of life, SWLS extended to life satisfaction, and ABIS for body image integration. Data on education, marriage, employment and parenthood were gathered. All the scores obtained were very close to normal references. The only gender difference was found for the TCI Cooperativeness scale, which was higher in women than in men. A satisfactory psychological well-being in terms of both self-esteem and integration of the prosthetic joint limb into one’s body image, with relatively limited amount of anxiety/depression, good quality of life, and good temperament and character traits, was found. No major gender differences were reported.