bluuebunny/crossref_metadata_2025 huggingface dataset:
The Association of Ethnicity and Oncologic Outcomes for Oral Cavity Squamous Cell Carcinoma (OSCC)
Authors: Mahboubi Kiana , Nakoneshny Steven C. , Sauro Khara , Roberts Samuel , Hart Rob , Matthews T. Wayne , Dort Joseph , Chandarana Shamir P.
Published: June 2024

(1) Background: To compare oncologic outcomes of South Asian (SA) patients treated for oral squamous cell carcinoma (OSCC) to the general population. (2) Methods: Adult patients who underwent surgical resection of OSCC +/− adjuvant treatment between 2009 and 2022 (N = 697) at a regional cancer centre in Canada were included. SA patients, identified using a validated method, were compared to non-SA patients. Kaplan–Meier methods were used to compare the primary outcomes, disease-specific survival (DSS) and recurrence-free survival (RFS) across baseline univariate characteristics, including betel nut consumption. Median follow-up time was 36.4 months. Cox proportional hazard models were used to identify independent predictors of survival with significance set at p < 0.05. (3) Results: SA patients (9% of cohort, N = 64) were significantly younger and had lower rates of smoking and alcohol consumption compared to non-SA patients (p < 0.05). SA patients had a two-fold higher risk of recurrence and significantly worse disease-specific survival, even after adjusting for stage and high-risk features [RFS: HR 2.01 (1.28–3.14), DSS: HR 1.79 (1.12–2.88)]. The consumption of betel nut was not associated with outcomes. (4) Conclusions: SA patients had significantly worse oncologic outcomes, even after controlling for known predictors of poor prognosis. These findings are novel and can inform personalized treatment decisions and influence public health policies when managing patients with different ethnic backgrounds.
The Many Roads from Alternative Splicing to Cancer: Molecular Mechanisms Involving Driver Genes
Authors: Gimeno-Valiente Francisco , López-Rodas Gerardo , Castillo Josefa , Franco Luis
Published: June 2024

Cancer driver genes are either oncogenes or tumour suppressor genes that are classically activated or inactivated, respectively, by driver mutations. Alternative splicing—which produces various mature mRNAs and, eventually, protein variants from a single gene—may also result in driving neoplastic transformation because of the different and often opposed functions of the variants of driver genes. The present review analyses the different alternative splicing events that result in driving neoplastic transformation, with an emphasis on their molecular mechanisms. To do this, we collected a list of 568 gene drivers of cancer and revised the literature to select those involved in the alternative splicing of other genes as well as those in which its pre-mRNA is subject to alternative splicing, with the result, in both cases, of producing an oncogenic isoform. Thirty-one genes fall into the first category, which includes splicing factors and components of the spliceosome and splicing regulators. In the second category, namely that comprising driver genes in which alternative splicing produces the oncogenic isoform, 168 genes were found. Then, we grouped them according to the molecular mechanisms responsible for alternative splicing yielding oncogenic isoforms, namely, mutations in cis splicing-determining elements, other causes involving non-mutated cis elements, changes in splicing factors, and epigenetic and chromatin-related changes. The data given in the present review substantiate the idea that aberrant splicing may regulate the activation of proto-oncogenes or inactivation of tumour suppressor genes and details on the mechanisms involved are given for more than 40 driver genes.
Past Happiness and Broken Future Horizon of Oncological Patients during Chemotherapy—A Quantitative Exploration of a Phenomenological Hypothesis
Authors: Fryze Magdalena , Wisniewska Patrycja , Wiertlewska-Bielarz Jadwiga , Moskalewicz Marcin
Published: June 2024

Understanding the impact of cancer on the experience of time is crucial in the context of hope and recovery. This study, a follow-up to a previous qualitative study of ovarian cancer patients – explored two types of such experiences—the memory of past happiness and the limited future planning. A sociodemographic questionnaire with nine questions about the experience of time was used on a convenience sample of 202 patients with various cancers, predominantly women with breast, ovarian, and cervical cancer. It was found that the respondents experienced increased focus on the present, decreased focus on the future, and a sense of unpredictability, with a relatively short temporal horizon measured in weeks and months, not years. Almost half of the respondents (46%) measured time during treatment by the rhythm of chemotherapy and check-ups, which thus appeared as the most meaningful events. The increase in the frequency with which patients underwent chemotherapy mildly affected their focus on the present (R = 0.25, p < 0.05), likely because of the discomfort of the side effects. The correlations between age and time in treatment, on the one hand, and the experience of time, on the other, were negligible. Changed temporal experience during chemotherapy is a factor that can have an impact on patients’ well-being and ability to cope with the disease. It thus should be taken into account when planning oncology care.
The Epidemiological Particularities of Malignant Hemopathies in French Guiana: 2005–2014
Authors: Nacher Mathieu , Wang Qiannan , Cenciu Beatrice , Aboikoni Alolia , Santa Florin , Quet Fabrice , Vergeade Fanja , Adenis Antoine , Deschamps Nathalie , Drak Alsibai Kinan
Published: June 2024

French Guiana is a French Overseas territory with singular features: it has a high prevalence of HIV and HTLV-1, its population is ethnically mixed, with widespread poverty, and up to 20% of the population lives in geographic isolation. In this context, we used registry data to estimate incidence and mortality due to hematological malignancies and to compare them with France and tropical Latin America. ICD codes C90 and C88 were compiled between 2005 and 2014. The direct standardization of age structure was performed using the world population. Survival analysis was performed, and Kaplan–Meier curves were drawn. The overall standardized incidence rate was 32.9 per 100,000 male years and 24.5 per 100,000 female years. Between 2005 and 2009, the standardized incidence rate was 29.6 per 100,000 among men and 23.6 per 100,000 among women, and between 2010 and 2014, it was 35.6 per 100,000 among men and 25.2 per 100,000 among women. Multiple myeloma/plasmocytoma and mature t/NK cell lymphomas, notably adult t-cell lymphoma/leukemia due to HTLV-1 infection, were the two most common hematologic malignancies and causes of death. Non-Hodgkin’s lymphoma incidence estimates were greater than global estimates. After adjusting for age, sex, and type of malignancy, people born in a foreign country independently had a poorer case-fatality rate, presumably reflecting difficulties in accessing care. The epidemiology of hematological malignancies in French Guiana has features that distinguish it from mainland France or from Latin America. The incidence of multiple myeloma and adult t-cell lymphoma/leukemia was significantly greater in French Guiana than in France or other Latin American countries.
End Organ Affection in Sickle Cell Disease
Authors: Bathla Tanvi , Lotfollahzadeh Saran , Quisel Matthew , Mehta Mansi , Malikova Marina , Chitalia Vipul C.
Published: June 2024

Sickle cell disease is an orphan disease affecting ethnic minorities and characterized by profound systemic manifestations. Although around 100,000 individuals with SCD are living in the US, the exact number of individuals is unknown, and it is considered an orphan disease. This single-gene disorder leads to red blood cell sickling and the deoxygenation of hemoglobin, resulting in hemolysis. SCD is associated with acute complications such as vaso-occlusive crisis, infections, and chronic target organ complications such as pulmonary disease and renal failure. While genetic therapy holds promise to alter the fundamental disease process, the major challenge in the field remains the target end organ damage and ways to mitigate or reverse it. Here, we provide an overview of the clinical manifestations and pathogenesis with a focus on end-organ damage and current therapeutic options, including recent FDA-approved stem cell and gene editing therapies.
Synergistic Steatosis Induction in Mice: Exploring the Interactions and Underlying Mechanisms between PFOA and Tributyltin
Authors: Dauwe Yannick , Mary Lucile , Oliviero Fabiana , Dubois Louise , Rousseau-Bacquie Elodie , Gomez Jelskey , Gayrard Véronique , Mselli-Lakhal Laïla
Published: June 2024

This study explores the impact of environmental pollutants on nuclear receptors (CAR, PXR, PPARα, PPARγ, FXR, and LXR) and their heterodimerization partner, the Retinoid X Receptor (RXR). Such interaction may contribute to the onset of non-alcoholic fatty liver disease (NAFLD), which is initially characterized by steatosis and potentially progresses to steatohepatitis and fibrosis. Epidemiological studies have linked NAFLD occurrence to the exposure to environmental contaminants like PFAS. This study aims to assess the simultaneous activation of nuclear receptors via perfluorooctanoic acid (PFOA) and RXR coactivation via Tributyltin (TBT), examining their combined effects on steatogenic mechanisms. Mice were exposed to PFOA (10 mg/kg/day), TBT (5 mg/kg/day) or a combination of them for three days. Mechanisms underlying hepatic steatosis were explored by measuring nuclear receptor target gene and lipid metabolism key gene expressions, by quantifying plasma lipids and hepatic damage markers. This study elucidated the involvement of the Liver X Receptor (LXR) in the combined effect on steatosis and highlighted the permissive nature of the LXR/RXR heterodimer. Antagonistic effects of TBT on the PFOA-induced activation of the Pregnane X Receptor (PXR) and Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) were also observed. Overall, this study revealed complex interactions between PFOA and TBT, shedding light on their combined impact on liver health.
Altered Extracellular Vesicle-Derived Protein and microRNA Signatures in Bronchoalveolar Lavage Fluid from Patients with Chronic Obstructive Pulmonary Disease
Authors: Bartel Sabine , Wolters Justina C. , Noor Hasnat , Rafie Karim , Fang Jiahua , Kirchner Benedikt , Nolte-′t Hoen Esther , Pfaffl Michael W. , Rutgers Steven , Timens Wim , van den Berge Maarten , Hylkema Machteld N.
Published: June 2024

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease for which there is no cure. Accumulating research results suggest a role for extracellular vesicles (EVs) in the pathogenesis of COPD. This study aimed to uncover the involvement of EVs and their molecular cargo in the progression of COPD by identification of EV-associated protein and microRNA (miRNA) profiles. We isolated EVs from the bronchial alveolar lavage fluid (BALF) of 18 patients with COPD and 11 healthy controls using size-exclusion chromatography. EV isolates were characterized using nanoparticle tracking analysis and protein content. Proteomic analysis revealed a higher abundance of 284 proteins (log2FC > 1) and a lower abundance of 3 proteins (log2FC < −1) in EVs derived from patients with COPD. Ingenuity pathway analysis showed that proteins enriched in COPD-associated EVs trigger inflammatory responses, including neutrophil degranulation. Variances in surface receptors and ligands associated with COPD EVs suggest a preferential interaction with alveolar cells. Small RNAseq analysis identified a higher abundance of ten miRNAs and a lower abundance of one miRNA in EVs from COPD versus controls (Basemean > 100, FDR < 0.05). Our data indicate that the molecular composition of EVs in the BALF of patients with COPD is altered compared to healthy control EVs. Several components in COPD EVs were identified that may perpetuate inflammation and alveolar tissue destruction.
CTHRC1: An Emerging Hallmark of Pathogenic Fibroblasts in Lung Fibrosis
Authors: Mukhatayev Zhussipbek , Adilbayeva Altynay , Kunz Jeannette
Published: June 2024

Pulmonary fibrosis is a chronic, progressive, irreversible lung disease characterized by fibrotic scarring in the lung parenchyma. This condition involves the excessive accumulation of extracellular matrix (ECM) due to the aberrant activation of myofibroblasts in the alveolar environment. Transforming growth factor beta (TGF-β) signaling is a crucial driver of fibrogenesis because it promotes excessive ECM deposition, thereby leading to scar formation and lung damage. A primary target of TGF-β signaling in fibrosis is Collagen Triple Helix Repeat Containing 1 (CTHRC1), a secreted glycoprotein that plays a pivotal role in ECM deposition and wound repair. TGF-β transcriptionally regulates CTHRC1 in response to tissue injury and controls the wound healing response through functional activity. CTHRC1 may also play an essential role in re-establishing and maintaining tissue homeostasis after wound closure by modulating both the TGF-β and canonical Wnt signaling pathways. This dual function suggests that CTHRC1 regulates tissue remodeling and homeostasis. However, deregulated CTHRC1 expression in pathogenic fibroblasts has recently emerged as a hallmark of fibrosis in multiple organs and tissues. This review highlights recent studies suggesting that CTHRC1 can serve as a diagnostic and prognostic biomarker for fibrosis in idiopathic pulmonary fibrosis, systemic sclerosis, and post-COVID-19 lung fibrosis. Notably, CTHRC1 expression is responsive to antifibrotic drugs that target the TGF-β pathway, such as pirfenidone and bexotegrast, indicating its potential as a biomarker of treatment success. These findings suggest that CTHRC1 may present new opportunities for diagnosing and treating patients with lung fibrosis.
Unraveling Verapamil’s Multidimensional Role in Diabetes Therapy: From β-Cell Regeneration to Cholecystokinin Induction in Zebrafish and MIN6 Cell-Line Models
Authors: Arefanian Hossein , Al Madhoun Ashraf , Al-Rashed Fatema , Alzaid Fawaz , Bahman Fatemah , Nizam Rasheeba , Alhusayan Mohammed , John Sumi , Jacob Sindhu , Williams Michayla R. , Abukhalaf Nermeen , Shenouda Steve , Joseph Shibu , AlSaeed Halemah , Kochumon Shihab , Mohammad Anwar , Koti Lubaina , Sindhu Sardar , Abu-Farha Mohamed , Abubaker Jehad , Thanaraj Thangavel Alphonse , Ahmad Rasheed , Al-Mulla Fahd
Published: June 2024

This study unveils verapamil’s compelling cytoprotective and proliferative effects on pancreatic β-cells amidst diabetic stressors, spotlighting its unforeseen role in augmenting cholecystokinin (CCK) expression. Through rigorous investigations employing MIN6 β-cells and zebrafish models under type 1 and type 2 diabetic conditions, we demonstrate verapamil’s capacity to significantly boost β-cell proliferation, enhance glucose-stimulated insulin secretion, and fortify cellular resilience. A pivotal revelation of our research is verapamil’s induction of CCK, a peptide hormone known for its role in nutrient digestion and insulin secretion, which signifies a novel pathway through which verapamil exerts its therapeutic effects. Furthermore, our mechanistic insights reveal that verapamil orchestrates a broad spectrum of gene and protein expressions pivotal for β-cell survival and adaptation to immune-metabolic challenges. In vivo validation in a zebrafish larvae model confirms verapamil’s efficacy in fostering β-cell recovery post-metronidazole infliction. Collectively, our findings advocate for verapamil’s reevaluation as a multifaceted agent in diabetes therapy, highlighting its novel function in CCK upregulation alongside enhancing β-cell proliferation, glucose sensing, and oxidative respiration. This research enriches the therapeutic landscape, proposing verapamil not only as a cytoprotector but also as a promoter of β-cell regeneration, thereby offering fresh avenues for diabetes management strategies aimed at preserving and augmenting β-cell functionality.
Embryos from Prepubertal Hyperglycemic Female Mice Respond Differentially to Oxygen Tension In Vitro
Authors: Predheepan Dhakshanya , Salian Sujith Raj , Uppangala Shubhashree , Lakshmi R Vani , Kalthur Guruprasad , Kovačič Borut , Adiga Satish Kumar
Published: June 2024

Reduced oxygen during embryo culture in human ART prevents embryo oxidative stress. Oxidative stress is also the major mechanism by which maternal diabetes impairs embryonic development. This study employed induced hyperglycemia prepubertal mice to mimic childhood diabetes to understand the effects of varying oxygen tension during in vitro embryonic development. The oocytes were fertilized and cultured at low (≈5%) oxygen (LOT) or atmospheric (≈20%) oxygen tension (HOT) for up to 96 h. Embryo development, apoptosis in blastocysts, inner cell mass (ICM) outgrowth proliferation, and Hif1α expression were assessed. Though the oocyte quality and meiotic spindle were not affected, the fertilization rate (94.86 ± 1.18 vs. 85.17 ± 2.81), blastocyst rate (80.92 ± 2.92 vs. 69.32 ± 2.54), and ICM proliferation ability (51.04 ± 9.22 vs. 17.08 ± 3.05) of the hyperglycemic embryos were significantly higher in the LOT compared to the HOT group. On the other hand, blastocysts from the hyperglycemic group, cultured at HOT, had a 1.5-fold increase in apoptotic cells compared to the control and lower Hif1α transcripts in ICM outgrowths compared to the LOT. Increased susceptibility of embryos from hyperglycemic mice to higher oxygen tension warrants the need to individualize the conditions for embryo culture systems in ART clinics, particularly when an endogenous maternal pathology affects the ovarian environment.
Structural Dynamics Analysis of USP14 Activation by AKT-Mediated Phosphorylation
Authors: Dash Raju , Tran Non-Nuoc , Lee Sung Bae , Lee Byung-Hoon
Published: June 2024

Ubiquitin-specific protease 14 (USP14), one of the three major proteasome-associated deubiquitinating enzymes (DUBs), is known to be activated by the AKT-mediated phosphorylation at Ser432. Thereby, AKT can regulate global protein degradation by controlling the ubiquitin-proteasome system (UPS). However, the exact molecular mechanism of USP14 activation by AKT phosphorylation at the atomic level remains unknown. By performing the molecular dynamics (MD) simulation of the USP14 catalytic domain at three different states (inactive, active, and USP14-ubiquitin complex), we characterized the change in structural dynamics by phosphorylation. We observed that the Ser432 phosphorylation induced substantial conformational changes of USP14 in the blocking loop (BL) region to fold it from an open loop into a β-sheet, which is critical for USP14 activation. Furthermore, phosphorylation also increased the frequency of critical hydrogen bonding and salt bridge interactions between USP14 and ubiquitin, which is essential for DUB activity. Structural dynamics insights from this study pinpoint the important local conformational landscape of USP14 by the phosphorylation event, which would be critical for understanding USP14-mediated proteasome regulation and designing future therapeutics.
Deregulation of Metalloproteinase Expression in Gray Horse Melanoma Ex Vivo and In Vitro
Authors: Brodesser Daniela M. , Kummer Stefan , Eichberger Julia A. , Schlangen Karin , Corteggio Annunziata , Borzacchiello Giuseppe , Bertram Christof A. , Brandt Sabine , Pratscher Barbara
Published: June 2024

The ability of human melanoma cells to switch from an epithelial to a mesenchymal phenotype contributes to the metastatic potential of disease. Metalloproteinases (MPs) are crucially involved in this process by promoting the detachment of tumor cells from the primary lesion and their migration to the vasculature. In gray horse melanoma, epithelial–mesenchymal transition (EMT) is poorly understood, prompting us to address MP expression in lesions versus intact skin by transcriptome analyses and the immunofluorescence staining (IF) of gray horse tumor tissue and primary melanoma cells. RNAseq revealed the deregulation of several MPs in gray horse melanoma and, notably, a 125-fold upregulation of matrix metalloproteinase 1 (MMP1) that was further confirmed by RT-qPCR from additional tumor material. The IF staining of melanoma tissue versus intact skin for MMP1 and tumor marker S100 revealed MMP1 expression in all lesions. The co-expression of S100 was observed at different extents, with some tumors scoring S100-negative. The IF staining of primary tumor cells explanted from the tumors for MMP1 showed that the metalloproteinase is uniformly expressed in the cytoplasm of 100% of tumor cells. Overall, the presented data point to MP expression being deregulated in gray horse melanoma, and suggest that MMP1 has an active role in gray horse melanoma by driving EMT-mediated tumor cell dissemination via the degradation of the extracellular matrix. Whilst S100 is considered a reliable tumor marker in human MM, gray horse melanomas do not seem to regularly express this protein.
Oncogenic Role of SATB2 In Vitro: Regulator of Pluripotency, Self-Renewal, and Epithelial–Mesenchymal Transition in Prostate Cancer
Authors: Yu Wei , Srivastava Rashmi , Srivastava Shivam , Ma Yiming , Shankar Sharmila , Srivastava Rakesh K.
Published: June 2024

Special AT-rich sequence binding protein-2 (SATB2) is a nuclear matrix protein that binds to nuclear attachment regions and is involved in chromatin remodeling and transcription regulation. In stem cells, it regulates the expression of genes required for maintaining pluripotency and self-renewal and epithelial–mesenchymal transition (EMT). In this study, we examined the oncogenic role of SATB2 in prostate cancer and assessed whether overexpression of SATB2 in human normal prostate epithelial cells (PrECs) induces properties of cancer stem cells (CSCs). The results demonstrate that SATB2 is highly expressed in prostate cancer cell lines and CSCs, but not in PrECs. Overexpression of SATB2 in PrECs induces cellular transformation which was evident by the formation of colonies in soft agar and spheroids in suspension. Overexpression of SATB2 in PrECs also resulted in induction of stem cell markers (CD44 and CD133), pluripotency-maintaining transcription factors (cMYC, OCT4, SOX2, KLF4, and NANOG), CADHERIN switch, and EMT-related transcription factors. Chromatin immunoprecipitation assay demonstrated that SATB2 can directly bind to promoters of BCL-2, BSP, NANOG, MYC, XIAP, KLF4, and HOXA2, suggesting SATB2 is capable of directly regulating pluripotency/self-renewal, cell survival, and proliferation. Since prostate CSCs play a crucial role in cancer initiation, progression, and metastasis, we also examined the effects of SATB2 knockdown on stemness. SATB2 knockdown in prostate CSCs inhibited spheroid formation, cell viability, colony formation, cell motility, migration, and invasion compared to their scrambled control groups. SATB2 knockdown in CSCs also upregulated the expression of E-CADHERIN and inhibited the expression of N-CADHERIN, SNAIL, SLUG, and ZEB1. The expression of SATB2 was significantly higher in prostate adenocarcinoma compared to normal tissues. Overall, our data suggest that SATB2 acts as an oncogenic factor where it is capable of inducing malignant changes in PrECs by inducing CSC characteristics.
Assessing Different Histological Preparations for Reconstruction of Astrocyte Tridimensional Structure
Authors: Barsanti Sara , Viana João Filipe , Veiga Alexandra , Machado João Luís , Abreu Daniela Sofia , Dias José Duarte , Monteiro Susana , Silva Nuno A. , Pinto Luísa , Oliveira João Filipe
Published: June 2024

Astrocytes are ubiquitous in the brain and spinal cord and display a complex morphology important for the local interactions with neighboring cells, resulting in the modulation of circuit function. Thus, studies focusing on astrocyte physiology in the healthy and diseased brain generally present analyses of astrocytic structure. The labeling method used to visualize the astrocytic structure defines the morphological level to observe and may vary depending on the anatomical sub-regions. The method choice may significantly affect our understanding of their structural diversity. The main goal of this work was to identify a straightforward and efficient protocol for labeling and reconstructing a detailed astrocytic structure to apply and validate in different brain tissue preparations across laboratories. For that, we explored different tissue processing protocols before GFAP labeling to determine the most effective method for reconstructing astrocytic backbones in the mouse hippocampus. Our results show that the reconstruction of astrocytic structure in vibratome sections labeled by free-floating immunofluorescence protocol provides a more practical method to achieve a higher level of detail and arbor complexity in astrocyte backbone reconstruction. Free-floating immunofluorescence labeling is the most reliable method for obtaining better antibody penetration and more detailed astrocyte structure. Finally, we also show that introducing an antigen retrieval step appears useful for visualizing more complete structural details.
Biosensors for Food Mycotoxin Determination: A Comparative and Critical Review
Authors: Pisoschi Aurelia Magdalena , Iordache Florin , Stanca Loredana , Mitranescu Elena , Bader Stoica Liliana , Geicu Ovidiu Ionut , Bilteanu Liviu , Serban Andreea Iren
Published: June 2024

The need for performant analytical methodologies to assess mycotoxins is vital, given the negative health impact of these compounds. Biosensors are analytical devices that consist of a biological element for recognizing the analyte and a transducer, which translates the biorecognition event into a signal proportional to the analyte concentration. The biorecognition elements can be enzymes, antibodies, or DNA fragments. The modalities of detection can be optical, electrochemical, thermal, or mass-sensitive. These analytical tools represent viable alternatives to laborious, expensive traditional methods and are characterized by specificity given by the biorecognition element, sensitivity, fast response, portability, multi-modal detection, and the possibility of in situ application. The present paper focuses on a comprehensive view, enriched with a critical, comparative perspective on mycotoxin assay using biosensors. The use of different biorecognition elements and detection modes are discussed comparatively. Nanomaterials with optical and electrochemical features can be exploited in association with a variety of biorecognition elements. Analytical parameters are reviewed along with a broad range of applications.
Minimal Access in Pediatric Surgery: An Overview on Progress towards Dedicated Instrument Developments and Anesthesiologic Advances to Enhance Safe Completion of Procedures
Authors: Pelizzo Gloria , Destro Francesca , Pierucci Ugo Maria , Costanzo Sara , Camporesi Anna , Diotto Veronica , Calcaterra Valeria , Saxena Amulya K.
Published: June 2024

Surgical techniques are evolving in Pediatric Surgery, especially in the area of minimal access surgery (MAS) where indications for applications are expanding. Miniaturization of instruments, using natural orifices, single incisions, or remotely controlled robot-assisted procedures, promises to increase the benefits of MAS procedures in pediatrics. Many pediatric pathologies are rare, and specialized surgical and anesthesiologic instruments are necessary to manage them, defined as “orphan devices”, for which development and dissemination on the market are slowed down or sometimes hindered by regulatory standards and limiting financial conflicts of interest. In pediatric surgery, it is of utmost importance to work in a multidisciplinary way to offer a surgical path that is safe and supported by technological advances. For this reason, optimizing pediatric anesthesia is also a crucial factor where technological advances have made monitoring more precise, thereby enhancing safety in the operative room. The development of customized instruments and technologies should be supported by pediatric research and should be adapted to the individualities of the small patient. This overview outlines the importance of dedicated instruments developed for the safe completion of MAS procedures in pediatrics.
Positive Youth Development, Mental Stress and Life Satisfaction in Middle School and High School Students in Portugal: Outcomes on Stress, Anxiety and Depression
Authors: Carvalho Marina , Branquinho Cátia , Moraes Barbara , Cerqueira Ana , Tomé Gina , Noronha Catarina , Gaspar Tânia , Rodrigues Nuno , Matos Margarida Gaspar de
Published: June 2024

The relation between positive youth development and stress, anxiety and depression was studied considering the mediator role of psychological symptoms and life satisfaction. A total of 3109 students included in the “Psychological Health and Well-being” study of the School Observatory participated, including 1618 females and 1491 males aged between 11 and 18 years old (M = 14.45; SD = 1.88), belonging to different school groups in different regions of the country. Adolescents with higher stress, depression and anxiety levels reported lower levels of competence, confidence and connection, as well as more psychological symptoms and lower life satisfaction. The results also showed that adolescents with higher levels of competence, confidence and connection reported less psychological symptoms and more life satisfaction. Two separate mediation analyses were performed to analyse the role of mental distress and life satisfaction on the relationship between positive youth development indicators and stress, anxiety and depression. These analyses confirmed the predicted relationships and partial mediations between mental distress and life satisfaction. These results should be taken into account in public policies concerning young people’s health and education that should involve both targeted and indicated prevention strategies, including school and community-based interventions, in order to be effective.
Small Peptide Derived from SFRP5 Suppresses Melanogenesis by Inhibiting Wnt Activity
Authors: Choi Yoon-Seo , Hong Jin-Gwen , Lim Dong-Young , Kim Min-Seo , Park Sang-Hoon , Kang Hee-Cheol , Seo Won-Sang , Lee Jongsung
Published: June 2024

Melanocytes, located in the epidermis’ basal layer, are responsible for melanin pigment production, crucial for skin coloration and protection against UV radiation-induced damage. Melanin synthesis is intricately regulated by various factors, including the Wnt signaling pathway, particularly mediated by the microphthalmia-associated transcription factor (MITF). While MITF is recognized as a key regulator of pigmentation, its regulation by the Wnt pathway remains poorly understood. This study investigates the role of Sfrp5pepD, a peptide antagonist of the Wnt signaling pathway, in modulating melanogenesis and its potential therapeutic implications for pigmentary disorders. To tackle this issue, we investigated smaller peptides frequently utilized in cosmetics or pharmaceuticals. Nevertheless, there is a significant scarcity of reports on peptides associated with melanin-related signal modulation or inhibiting melanin production. Results indicate that Sfrp5pepD effectively inhibits Wnt signaling by disrupting the interaction between Axin-1 and β-catenin, thus impeding downstream melanogenic processes. Additionally, Sfrp5pepD suppresses the interaction between MITF and β-catenin, inhibiting their nuclear translocation and downregulating melanogenic enzyme expression, ultimately reducing melanin production. These inhibitory effects are validated in cell culture models suggesting potential clinical applications for hyperpigmentation disorders. Overall, this study elucidates the intricate interplay between Wnt signaling and melanogenesis, highlighting Sfrp5pepD as a promising therapeutic agent for pigmentary disorders. Sfrp5pepD, with a molecular weight of less than 500 Da, is anticipated to penetrate the skin unlike SFRPs. This suggests a strong potential for their use as cosmetics or transdermal absorption agents. Additional investigation into its mechanisms and clinical significance is necessary to enhance its effectiveness in addressing melanin-related skin conditions.
Molecular Mechanisms in the Design of Novel Targeted Therapies for Neurodegenerative Diseases
Authors: Nowak Ilona , Paździor Marlena , Sarna Robert , Madej Marcel
Published: June 2024

Neurodegenerative diseases are a diverse group of diseases characterized by a progressive loss of neurological function due to damage to nerve cells in the central nervous system. In recent years, there has been a worldwide increase in the expanding associated with increasing human life expectancy. Molecular mechanisms control many of the essential life processes of cells, such as replication, transcription, translation, protein synthesis and gene regulation. These are complex interactions that form the basis for understanding numerous processes in the organism and developing new diagnostic and therapeutic approaches. In the context of neurodegenerative diseases, molecular basis refers to changes at the molecular level that cause damage to or degeneration of nerve cells. These may include protein aggregates leading to pathological structures in brain cells, impaired protein transport in nerve cells, mitochondrial dysfunction, inflammatory processes or genetic mutations that impair nerve cell function. New medical therapies are based on these mechanisms and include gene therapies, reduction in inflammation and oxidative stress, and the use of miRNAs and regenerative medicine. The aim of this study was to bring together the current state of knowledge regarding selected neurodegenerative diseases, presenting the underlying molecular mechanisms involved, which could be potential targets for new forms of treatment.
Application of the TaqMan ARMS-PCR Approach for Genotyping Drug-Induced Hearing Loss Using Dried Blood Samples
Authors: Tan Jiefeng , Zhang Xiaoqing , Wei Xue , Ding Min
Published: June 2024

A single nucleotide variant in mitochondrial DNA (mtDNA) 1555A>G is associated with drug-induced hearing loss. For the 1555A>G mutation site, 1555A wild-type and 1555G mutant-type plasmids were constructed, respectively. In this study, a PCR method based on the TaqMan amplification refractory mutation system was proposed to detect mtDNA 1555A>G. A common upstream primer, a common TaqMan probe, and two downstream allele-specific primers with mismatched bases were designed. One-step amplification and detection of the wild-type and mutant type at the 1555 site were realized for the deafness-related gene through two reactions. Based on this detection method, the minimum detection limit of the wild-type and mutant type detection systems for plasmids was 50 copies/μL. The minimum sensitivity for the detection of nucleic acids in real dried blood spot (DBS) samples was 0.1 ng/μL. In the normal DBS DNA sample, the detection limit of the mutation abundance reached 0.78%. The specificity of the detection method was 100%, and the coefficient of variation was less than 3.36%. This approach was validated using clinical DNA extracted from 113 DBS samples of newborns. Additionally, it showed 100% agreement with bi-directional Sanger sequencing. It can be used as an optional method for the clinical detection of deafness-related genes.
Sugarcane Bagasse: Challenges and Opportunities for Waste Recycling
Authors: Hiranobe Carlos T. , Gomes Andressa S. , Paiva Fábio F. G. , Tolosa Gabrieli R. , Paim Leonardo L. , Dognani Guilherme , Cardim Guilherme P. , Cardim Henrique P. , dos Santos Renivaldo J. , Cabrera Flávio C.
Published: June 2024

Sugarcane has primarily been used for sugar and ethanol production. It creates large quantities of residual lignocellulosic biomass such as sugarcane bagasse, leaves, tops, and vinasse. Biomass is a sustainable prospect for biorefineries aiming to optimize production processes. We detail recent research developments in recycling sugarcane, including energy generation and pyrolysis to obtain biofuels, for example. To produce biochar, the energy cost of operating at high temperatures and large-scale production remain as obstacles. The energy generation prospects can be enhanced by pellet production; however, it requires an improvement in quality control for long-term storage or long-distance transportation. In civil construction, the materials still need to prove their long-term efficiency and reliability. Related to adsorbent materials, the use of sugarcane bagasse has the advantage of being low-cost and environmentally friendly. Nevertheless, the extraction, functionalization, and modification of cellulose fibers, to improve their adsorption properties or even mode of operation, still challenges. The synthesis of nanostructures is still lacking high yields and the ability to scale up. Finally, controlling dispersion and orientation and avoiding fiber agglomeration could improve the mechanical response of composites using sugarcane bagasse. The different possibilities for using sugarcane and its residues reinforce the importance of this material for the industry and the global economy. Thus, the present work addresses current challenges and perspectives of different industrial processes involving sugarcane aiming to support future research on waste-derived subjects.
The Effect of Isotretinoin on Insulin Resistance and Serum Adiponectin Levels in Acne Vulgaris Patients: A Systematic Review and Meta-Analysis
Authors: Paschalidou Eleni , Katsaras Georgios , Papoulakis Thomas , Kalloniati Evangelia , Kavvadas Dimitrios , Karachrysafi Sofia , Kapoukranidou Dorothea , Tagarakis Georgios , Papamitsou Theodora
Published: June 2024

Background: Isotretinoin is the drug of choice for severe acne. We sought to examine the potential link between isotretinoin and insulin resistance. Methods: We conducted a systematic review and meta-analysis in accordance with the PRISMA statement. A comprehensive search of the PubMed/MEDLINE, SCOPUS, and Cochrane databases was performed until 12 January 2022 utilizing the PICO (Patient, Intervention, Comparison, Outcome) tool. Fifteen English-language studies focusing on isotretinoin-treated acne patients were included. Serum levels of insulin, glucose, and adiponectin were evaluated before and after treatment, and insulin sensitivity was assessed using the HOMA–IR. A meta-analysis was conducted using RevMan 5.4.1 software, and a quality assessment was undertaken using the ROBINS-I tool. Results: The meta-analysis unveiled a statistically significant rise in the post-treatment levels of adiponectin, an anti-inflammatory agent, which inhibits liver glucose production while enhancing insulin sensitivity (SMD = 0.86; 95% confidence interval (95% CI) = 0.48–1.25, p-value < 0.0001; I2 = 58%). Our subgroup analysis based on study type yielded consistent findings. However, no statistically significant outcomes were observed for insulin, glucose levels, and the HOMA-IR. Conclusions: There is not a clear association between isotretinoin and insulin resistance, but it appears to enhance the serum levels of adiponectin, which participates in glucose metabolism.
Early Screening for Long QT Syndrome and Cardiac Anomalies in Infants: A Comprehensive Study
Authors: Nosetti Luana , Zaffanello Marco , Lombardi Carolina , Gerosa Alessandra , Piacentini Giorgio , Abramo Michele , Agosti Massimo
Published: June 2024

(1) Background: Sudden Infant Death Syndrome (SIDS) represents sudden and unexplained deaths during the sleep of infants under one year of age, despite thorough investigation. Screening for a prolonged QTc interval, a marker for Long QT Syndrome (LQTS), should be conducted on all newborns to reduce the incidence of SIDS. Neonatal electrocardiograms (ECGs) could identify congenital heart defects (CHDs) early, especially those not detected at birth. Infants with prolonged QTc intervals typically undergo genetic analysis for Long QT Syndrome. (2) Methods: The study involved infants aged 20–40 days, born with no apparent clinical signs of heart disease, with initial ECG screening. Infants with prenatal diagnoses or signs/symptoms of CHDs identified immediately after birth, as well as infants who had previously had an ECG or echocardiogram for other medical reasons, were excluded from the study. We used statistical software (SPSS version 22.0) to analyze the data. (3) Results: Of the 42,200 infants involved, 2245 were enrolled, with 39.9% being males. Following this initial screening, 164 children (37.8% males) with prolonged QTc intervals underwent further evaluation. Out of these 164 children, 27 children were confirmed to have LQTS. However, only 18 children were finally investigated for genetic mutations, and mutations were identified in 11 tests. The most common mutations were LQT1 (54.5%), LQT2 (36.4%), and LQT3 (1 patient). Treatment options included propranolol (39.8%), nadolol (22.2%), inderal (11.1%), metoprolol (11.1%), and no treatment (16.7%). The most common abnormalities were focal right bundle branch block (54.5%), left axis deviation (9.2%), and nonspecific ventricular repolarization abnormalities (7.1%). Multiple anomalies were found in 0.47% of children with focal right bundle branch block. Structural abnormalities were associated with specific features in 267 patients (11.9%), primarily isolated patent foramen ovale (PFO) at 61.4%. (4) Conclusions: This screening approach has demonstrated effectiveness in the early identification of LQTS and other cardiac rhythm anomalies, with additional identification of mutations and/or prolonged QTc intervals in family members. Identifying other ECG abnormalities and congenital heart malformations further enhances the benefits of the screening.
Identification of Elastoplastic Constitutive Model of GaN Thin Films Using Instrumented Nanoindentation and Machine Learning Technique
Authors: Khalfallah Ali , Khalfallah Amine , Benzarti Zohra
Published: June 2024

This study presents a novel inverse identification approach to determine the elastoplastic parameters of a 2 µm thick GaN semiconductor thin film deposited on a sapphire substrate. This approach combines instrumented nanoindentation with finite element (FE) simulations and an artificial neural network (ANN) model. Experimental load–depth curves were obtained using a Berkovich indenter. To generate a comprehensive database for the inverse analysis, FE models were constructed to simulate load–depth responses across a wide range of GaN thin film properties. The accuracy of both 2D and 3D simulations was compared to select the optimal model for database generation. The Box–Behnken design-based data sampling method was used to define the number of simulations and input variables for the FE models. The ANN technique was then employed to establish the complex mapping between the simulated load–depth curves (input) and the corresponding stress–strain curve (output). The generated database was used to train and test the ANN model. Then, the learned ANN model was used to achieve high accuracy in identifying the stress–strain curve of the GaN thin film from the experimental load–depth data. This work demonstrates the successful application of an inverse analysis framework, combining experimental nanoindentation tests, FE modeling, and an ANN model, for the characterization of the elastoplastic behavior of GaN thin films.
A Comparative Study of Machining Property in Inconel 718 Superalloy Grinding with Al2O3- and CBN/Fe-Based Spherical Magnetic Abrasives
Authors: Jiang Linzhi , Zhang Guixiang , Zhang Haozhe , Xia Yandan , Xiang Jinli
Published: June 2024

A comparative analysis was studied on the finishing performance of spherical CBN/Fe-based magnetic abrasive particles (MAPs) and Al2O3/Fe-based magnetic abrasive particles (MAPs) prepared by the gas atomization method in the magnetic abrasive finishing (MAF) of the Inconel 718 superalloy. In the MAF, it was found that compared with Al2O3/Fe-based MAPs, CBN/Fe-based MAPs have a lower grinding temperature and generate less heat during the grinding of the Inconel 718 superalloy. The grinding pressure generated on the workpiece is relatively stable (Al2O3/Fe-based MAPs have a larger fluctuation range of grinding pressure on the workpiece surface during the grinding process). The surface roughness of the workpiece rapidly drops from Ra 0.57 μm to Ra 0.039 μm, and the material removal reaches 42 mg within 20 min. After finishing, the scratches on the surface of the workpiece basically disappear, the contour curve is relatively flat, and there is almost no adhesion on the surface of the workpiece. The mirror effect of the superalloy surface is good, and ultimately a better surface quality can be obtained.
Predicting New Single/Multiphase-Structure High-Entropy Alloys Using a Pattern Recognition Network
Authors: Wang Fang , Wang Jiahao , Wang Jiayu , Wu Ruirui , Liu Ke
Published: June 2024

Machine learning methods were employed to predict the phase structures of high-entropy alloys (HEAs). These alloys were classified into four categories: bcc (body-centered cubic), fcc (face-centered cubic), bcc+fcc (body-centered cubic and face-centered cubic) and others (containing intermetallic compounds and other structural alloys). The utilized algorithm was a Pattern Recognition Network (PRN) utilizing cross-entropy as the loss function, enabling the prediction of HEAs’ phase formation probability. The PRN algorithm demonstrated an accuracy exceeding 87% based on the test data. The PRN algorithm successfully predicted the transformation from fcc to fcc+bcc and subsequently to a bcc structure with the increase in Al content in AlxCoCu6Ni6Fe6 and AlxCoCrCuNiFe HEAs. In addition, AlxCoCu6Ni6Fe6 (x = 1, 3, 6, 9) HEAs were prepared using a vacuum arc furnace, and the microstructure of the as-cast alloy was tested by means of XRD, SEM, and EBSD, confirming the high consistency between the predicted and observed phase structures. This study showcases the efficacy of the PRN algorithm in predicting both single- and multiphase-structure high-entropy alloys, offering valuable insights into alloy design and development.
Study of the Performance of Emulsified Asphalt Shotcrete in High-Altitude Permafrost Regions
Authors: Hou Yitong , Niu Kaimin , Tian Bo , Li Xueyang , Chen Junli
Published: June 2024

To improve the performance of shotcrete in high-altitude and low-temperature environments, emulsified asphalt shotcrete (EASC), which can be used in negative-temperature environments, was prepared by using low-freezing-point emulsified asphalt, calcium aluminate cement, and sodium pyrophosphate as modified materials. The effect of emulsified asphalt on the performance of shotcrete was investigated through concrete spraying and indoor tests. Then, the modification mechanism of emulsified asphalt with respect to EASC was analyzed by combining scanning electron microscopy images and the pore structure characteristics of EASC. The results showed that in a negative-temperature environment, the incorporation of emulsified asphalt delayed the formation of the peak of the cement hydration exotherm, slowed the rate of the cement hydration exotherm, reduced the thermal perturbation of permafrost by EASC, increased the cohesion of the concrete, improved the bond strength between EASC and permafrost, and reduced the rate of rebound. The mechanical strength of the studied EASC decreased upon increasing the amount of emulsified asphalt in the admixture, and its resistance to cracking gradually improved. A content of less than 5% emulsified asphalt could improve the internal pore structure of EASC, thus improving its durability. Increasing the content of emulsified asphalt affected the hydration process of the cement, and the volume content of the capillary pores and macropores increased, which reduced the durability of the EASC.