bluuebunny/crossref_metadata_2025 huggingface dataset:
Beneficial Effects of Lactobacilli Species on Intestinal Homeostasis in Low-Grade Inflammation and Stress Rodent Models and Their Implication in the Modulation of the Adhesive Junctional Complex
Authors: Chamignon Célia , Mallaret Geoffroy , Rivière Julie , Vilotte Marthe , Chadi Sead , de Moreno de LeBlanc Alejandra , LeBlanc Jean Guy , Carvalho Frédéric Antonio , Pane Marco , Mousset Pierre-Yves , Langella Philippe , Lafay Sophie , Bermúdez-Humarán Luis G.
Published: August 2023

Intestinal barrier integrity is essential in order to maintain the homeostasis of mucosal functions and efficient defensive reactions against chemical and microbial challenges. An impairment of the intestinal barrier has been observed in several chronic diseases. The gut microbiota and its impact on intestinal homeostasis is well described and numerous studies suggest the ability of some probiotic strains to protect the intestinal epithelial integrity and host homeostasis. In this work, we aimed to assess the beneficial effects of three Lactobacillus strains (Lacticaseibacillus rhamnosus LR04, Lacticaseibacillus casei LC03, and Lactiplantibacillus plantarum CNCM I-4459) and their mechanism of action in low-grade inflammation or neonatal maternal separation models in mice. We compared the impact of these strains to that of the well-known probiotic Lacticaseibacillus rhamnosus GG. Our results demonstrated that the three strains have the potential to restore the barrier functions by (i) increasing mucus production, (ii) restoring normal permeability, and (iii) modulating colonic hypersensitivity. Moreover, gene expression analysis of junctional proteins revealed the implication of Claudin 2 and Cingulin in the mechanisms that underlie the interactions between the strains and the host. Taken together, our data suggest that LR04, CNCM I-4459, and LC03 restore the functions of an impaired intestinal barrier.
Lateral Flow Assay: A Summary of Recent Progress for Improving Assay Performance
Authors: Omidfar Kobra , Riahi Fatemeh , Kashanian Soheila
Published: August 2023

Lateral flow tests are one of the most important types of paper-based point-of-care (POCT) diagnostic tools. It shows great potential as an implement for improving the rapid screening and management of infections in global pandemics or other potential health disorders by using minimally expert staff in locations where no sophisticated laboratory services are accessible. They can detect different types of biomarkers in various biological samples and provide the results in a little time at a low price. An important challenge regarding conventional LFAs is increasing their sensitivity and specificity. There are two main approaches to increase sensitivity and specificity, including assay improvement and target enrichment. Assay improvement comprises the assay optimization and signal amplification techniques. In this study, a summarize of various sensitivity and specificity enhancement strategies with an objective evaluation are presented, such as detection element immobilization, capillary flow rate adjusting, label evolution, sample extraction and enrichment, etc. and also the key findings in improving the LFA performance and solving their limitations are discussed along with numerous examples.
Lower Serum Iron Level Predicts Postoperative Global Cerebral Edema Following Aneurysmal Subarachnoid Hemorrhage
Authors: Wang Haojie , Zheng Shufa , Zhang Yibin , Fan Wenjian , Xie Bingsen , Chen Fuxiang , Lin Yuanxiang , Kang Dezhi
Published: August 2023

Background: Iron plays an important role in neuronal injury and edema formation after intracranial hemorrhage. However, the role of serum iron in aneurysmal subarachnoid hemorrhage (aSAH) is yet to be well-established. This study aims to identify whether serum iron could predict postoperative global cerebral edema (GCE) and poor outcome in aSAH. Methods: 847 patients’ aSAH clinical data were retrospectively collected at the First Affiliated Hospital of Fujian Medical University. Data on demographics, clinical characteristics, and laboratory values were collected and analyzed through univariate and multivariate analyses. Propensity score matching (PSM) analysis was performed to balance the baseline differences between the groups. Results: The incidence of high-grade global cerebral edema (H-GCE) following aSAH was 12.99% (110/847). Serum iron levels [odds ratio (OR) = 1.143; 95% confidence interval (CI), (1.097–1.191); p < 0.001] were associated with the occurrence of H-GCE following aSAH in the univariate analysis. This association remained statistically significant even after adjusting for other variables in the multivariate model, with serum iron having an OR of 1.091 (95% CI, 1.043–1.141; p < 0.001) for GCE. After 1:1 PSM, serum iron levels ≤ 10.7 µmol/L remained a significant independent predictor of GCE (p = 0.002). The receiver operating characteristic (ROC) curve analysis determined that a serum iron cut-off value of ≤ 10.7 µmol/L was optimal for predicting H-GCE [Areas under the ROC curves (AUC) = 0.701, 95% CI, (0.669–0.732), p < 0.001; sensitivity, 67.27%; specificity, 63.77%] in patients with aSAH. Additionally, a trend was observed in which higher Hunt-Hess grades (HH grade) were associated with lower serum iron levels, and higher modified Fisher grades (mFisher grade) were associated with lower serum iron levels. In addition, the serum iron level was also associated with a 3-month functional neurological outcome (p < 0.001). Conclusions: The results of this study indicate that a decreased serum iron level serves as a clinically significant biomarker for the prediction of postoperative GCE and a poor outcome at 3-months in patients with aSAH.
Real and Deepfake Face Recognition: An EEG Study on Cognitive and Emotive Implications
Authors: Tarchi Pietro , Lanini Maria Chiara , Frassineti Lorenzo , Lanatà Antonio
Published: August 2023

The human brain’s role in face processing (FP) and decision making for social interactions depends on recognizing faces accurately. However, the prevalence of deepfakes, AI-generated images, poses challenges in discerning real from synthetic identities. This study investigated healthy individuals’ cognitive and emotional engagement in a visual discrimination task involving real and deepfake human faces expressing positive, negative, or neutral emotions. Electroencephalographic (EEG) data were collected from 23 healthy participants using a 21-channel dry-EEG headset; power spectrum and event-related potential (ERP) analyses were performed. Results revealed statistically significant activations in specific brain areas depending on the authenticity and emotional content of the stimuli. Power spectrum analysis highlighted a right-hemisphere predominance in theta, alpha, high-beta, and gamma bands for real faces, while deepfakes mainly affected the frontal and occipital areas in the delta band. ERP analysis hinted at the possibility of discriminating between real and synthetic faces, as N250 (200–300 ms after stimulus onset) peak latency decreased when observing real faces in the right frontal (LF) and left temporo-occipital (LTO) areas, but also within emotions, as P100 (90–140 ms) peak amplitude was found higher in the right temporo-occipital (RTO) area for happy faces with respect to neutral and sad ones.
Exploring Risk Factors Affecting Sustainable Outcomes of Global Public–Private Partnership (PPP) Projects: A Stakeholder Perspective
Authors: Li Zilin , Wang Haotian
Published: August 2023

As a model for delivering infrastructure initiatives, public–private partnerships (PPPs) have gained significant popularity in recent years. The globalization of PPP has exposed them to elevated risks emanating from the international real economy and financial market, which can ultimately result in project cancellations or distress. This study analyzes risk factors affecting the sustainable outcomes of global PPP projects from a stakeholder perspective. After identifying the interests of key stakeholders and examining how various risks influence stakeholders’ interests, a two-step binomial probit model is used to investigate domestic and international risk factors in PPP arrangements based on the World Bank PPI database. The empirical results indicate that inflation has a substantially positive effect on project failure, while factors such as PPP experience, central government involvement, exchange rate fluctuations, etc., significantly contribute to PPP success. In addition, the study demonstrates that trade openness and net foreign direct investment (FDI) inflow are crucial for the transmission of global risks. The study also provides policy implications and recommendations from a risk allocation–stakeholder relationship perspective to enhance the resilience of PPP initiatives based on these findings.
A Decision Support System for Organizing Quality Control of Buildings Construction during the Rebuilding of Destroyed Cities
Authors: Lapidus Azariy , Makarov Aleksandr , Kozlova Anastasiia
Published: August 2023

Natural disasters and warfare lead to the destruction of city buildings and infrastructure, leaving large numbers of people homeless. The rebuilding of destroyed cities needs to be carried out promptly while maintaining a balance between construction quality and duration. Rework due to defects and the lengthy approval of non-conformances significantly increases the duration of construction. This study aimed to develop a decision support system to fix or negotiate strategies to address construction defects, depending on their level of risk. The paper addresses the following objectives: classifying defects by the quality of construction that they affect; building a tree of construction defect risks; and developing an artificial neural network (ANN) to assess the defect risk. The weights of the links are represented by posterior probabilities of damage calculated using the Bayes’ theorem in the pre-training stage. The ANN has been adapted to cast-in-place reinforced concrete structures. When training the resulting ANN on a sample of precedents, the test sample demonstrated convergence and low errors. The resulting model will accelerate construction by automating assessments of defect severity and reducing the time spent on reworking defects with low quality risk.
Experimental Study of the Bending Performance of Cold-Formed Steel Channel Beams Considering the Corner Hardening Effect
Authors: Liu Rong-Gui , Xu Bo , Zhang Feng , Peng Sheng-Nan , Yang Chen , Chen Mao-Wei , Chen Su-Hang , Xie Ming-Zhi
Published: August 2023

Cold-formed steel channel beam components are increasingly used in lightweight steel buildings owing to the high strength–weight ratio. However, the influence of cold working processes, in relation to corner regions, and how this impacts the bending behavior of channel beams lacks thorough evaluation. In the present study, a series of coupon and bending tests were conducted and the numerical simulation and analytical derivation were supplemented, aiming to investigate the bending performance of cold-formed steel channel beams considering the reinforcement effect in corner regions. The results show that the engineering stress–strain relationships of the flat and corner coupons conformed to the trilinear models with different characteristic parameters. The yielding and ultimate strengths of the corner specimens was increased by 50% and 7%, respectively, compared to the flat coupons due to the cold-bending technique. The strain distribution of the cold-formed channel beams accord with the plane section while the stresses at the corners were 35% higher than those at the flanges, indicting the different mechanical response of the flat and corner regions. The component-based model for cold-formed steel channel beams was established to exactly describe the influence of the cold-bending action, which was greatly validated by the experimental and numerical data with the errors of typical parameters less than 9%.
Administration of Enfortumab Vedotin after Immune-Checkpoint Inhibitor and the Prognosis in Japanese Metastatic Urothelial Carcinoma: A Large Database Study on Enfortumab Vedotin in Metastatic Urothelial Carcinoma
Authors: Kawahara Takashi , Hasizume Akihito , Uemura Koichi , Yamaguchi Katsuya , Ito Hiroki , Takeshima Teppei , Hasumi Hisashi , Teranishi Jun-ichi , Ousaka Kimito , Makiyama Kazuhide , Uemura Hiroji
Published: August 2023

Background: Enfortumab vedotin shows promise as a targeted therapy for advanced urothelial carcinoma, particularly in patients who have previously received platinum-based chemotherapy and an immune-checkpoint inhibitor. The EV-301 phase III trial demonstrated significantly improved overall survival and response rates compared to standard chemotherapy. However, more data, especially from larger real-world studies, are needed to further assess its effectiveness in Japanese patients. Methods: A total of 6007 urothelial cancer patients inducted with pembrolizumab as a second-line treatment were analyzed. Among them, 563 patients received enfortumab vedotin after pembrolizumab, while 443 patients received docetaxel or paclitaxel after pembrolizumab, and all were included in the study for efficacy as a life prolonging agent. Results: The enfortumab vedotin group showed a longer overall survival than the paclitaxel/docetaxel group (p = 0.013, HR: 0.71). In multivariate analysis, enfortumab vedotin induction was the independent risk factor for overall survival (p = 0.013, HR: 0.70). There were no significant differences in cancer-specific survival. Conclusions: Enfortumab vedotin prolonged the overall survival for Japanese advanced or metastatic urothelial carcinoma patients compared to paclitaxel or docetaxel after pembrolizumab treatment.
ARID1B Immunohistochemistry Is an Important Test for the Diagnosis of Dedifferentiated and Undifferentiated Gynecologic Malignancies
Authors: Tessier-Cloutier Basile
Published: August 2023

Dedifferentiated and undifferentiated endometrial and ovarian carcinomas (DDC/UDC) are aggressive malignancies defined by morphologic and molecular undifferentiation, and associated with core SWI/SNF deficiency. Their main differential diagnoses include high-grade endometrial and ovarian carcinomas that often show overlapping morphologic and molecular profiles. Loss of cell lineage markers expression by immunohistochemistry (IHC) is commonly used to assist diagnosis, but it has poor specificity, while core SWI/SNF deficiency is much more specific. Approximately half of SWI/SNF-deficient DDC/UDC are associated with loss of ARID1B expression, yet, unlike the other core SWI/SNF proteins (SMARCA4 and SMARCB1), this test is rarely available, even in tertiary centers. Mutational testing for ARID1B is increasingly common among targeted DNA sequencing panels, but it is difficult to interpret in the absence of IHC results. Overall, the importance of including ARID1B IHC as part of the routine panel for undifferentiated gynecologic malignancies should be emphasized, especially as SWI/SNF inactivation is becoming a necessary biomarker for diagnostics, clinical management, and clinical trial enrollment.
Proteomic Profile Distinguishes New Subpopulations of Breast Cancer Patients with Different Survival Outcomes
Authors: Tobiasz Joanna , Polanska Joanna
Published: August 2023

As a highly heterogeneous disease, breast cancer (BRCA) demonstrates a diverse molecular portrait. The well-established molecular classification (PAM50) relies on gene expression profiling. It insufficiently explains the observed clinical and histopathological diversity of BRCAs. This study aims to demographically and clinically characterize the six BRCA subpopulations (basal, HER2-enriched, and four luminal ones) revealed by their proteomic portraits. GMM-based high variate protein selection combined with PCA/UMAP was used for dimensionality reduction, while the k-means algorithm allowed patient clustering. The statistical analysis (log-rank and Gehan–Wilcoxon tests, hazard ratio HR as the effect size ES) showed significant differences across identified subpopulations in Disease-Specific Survival (p = 0.0160) and Progression-Free Interval (p = 0.0264). Luminal subpopulations vary in prognosis (Disease-Free Interval, p = 0.0277). The A2 subpopulation is of the poorest, comparable to the HER2-enriched subpopulation, prognoses (HR = 1.748, referenced to Luminal B, small ES), while A3 is of the best (HR = 0.250, large ES). Similar to PAM50 subtypes, no substantial dependency on demographic and clinical factors was detected across Luminal subpopulations, as measured by χ2 test and Cramér’s V for ES, and ANOVA with appropriate post hocs combined with η2 or Cohen’s d-type ES, respectively. Progesterone receptors can serve as the potential A2 biomarker within Luminal patients. Further investigation of molecular differences is required to examine the potential prognostic or clinical applications.
Monitoring of Plasma EGFR Mutations during Osimertinib Treatment for NSCLC Patients with Acquired T790M Mutation
Authors: Watanabe Kana , Saito Ryota , Miyauchi Eisaku , Nagashima Hiromi , Nakamura Atsushi , Sugawara Shunichi , Tanaka Nobuyuki , Terasaki Hiroshi , Fukuhara Tatsuro , Maemondo Makoto
Published: August 2023

Background: Osimertinib was first approved for the treatment of non-small cell lung cancer (NSCLC) in patients who have developed the epidermal growth factor receptor (EGFR) T790M mutation after treatment with EGFR tyrosine kinase inhibitors (TKIs). We routinely evaluated the plasma of NSCLC patients with the T790M mutation to more rapidly detect an increase in disease activity and resistance to treatment. Methods: Eligible patients received osimertinib after resistance to the first- or second-generation of EGFR-TKIs in NSCLC harboring T790M mutation detectable in tumor tissue or plasma. Plasma samples were collected every 8 weeks during osimertinib treatment. The plasma analysis was performed using an improved PNA-LNA PCR clamp method. We tested samples for a resistance mechanism, including EGFR-activating, T790M, and C797S mutations, and assessed the association between the mutations and osimertinib treatment. Results: Of the 60 patients enrolled in the study, 58 were eligible for this analysis. In plasma collected before osimertinib treatment, activating mutations were detected in 47 of 58 patients (81.0%) and T790M was detected in 44 patients (75.9%). Activating mutations were cleared in 60.9% (28/46) and T790M was cleared in 93.0% (40/43). Of these, 71.4% (20/28) of activating mutations and 87.5% (35/40) of T790M mutation were cleared within 8 weeks of treatment. The total response rate (RR) was 53.4% (31/58). The median duration of treatment was 259 days, with a trend toward longer treatment duration in patients who experienced the clearance of activating mutations with osimertinib. At the time of disease progression during osimertinib treatment, C797S was detected in 3 of 37 patients (8.1%). Conclusion: Plasma EGFR mutation analysis was effective in predicting the effect of osimertinib treatment.
Radiotherapy and Systemic Therapies: Focus on Head and Neck Cancer
Authors: De Felice Francesca , Cattaneo Carlo Guglielmo , Franco Pierfrancesco
Published: August 2023

Head and neck squamous cell carcinoma (HNSCC) is a complex clinical entity, and its treatment strategy remains a challenge. The best practice management for individual HNSCC patients should be discussed within a multidisciplinary team. In the locally advanced disease, radiation therapy (RT) with or without concomitant cisplatin-based chemotherapy is the current standard of care for most patients treated definitively or adjuvantly after surgery. Intensity-modulated photon therapy (IMRT) is the recommended RT technique due to its ability to offer considerable treatment conformality while sparing surrounding normal critical tissues. At present, the development of novel treatment strategies, as well as alternative systemic agent combinations, is an urgent need to improve the therapeutic ratio in HNSCC patients. Despite the immune landscape suggesting a strong rationale for the use of immunotherapy agents in HNSCC, evidence-based data demonstrate that combining RT with immune checkpoint inhibitors as the primary treatment modality has not been shown to induce significant benefit on survival clinical outcomes. The objective of this article is to review the current literature on the treatment of patients with HNSCC. We initially provided a comprehensive overview of the standard of care. We then focused on the integration of systemic therapies with RT, highlighting the latest published evidence and ongoing trials which investigate different combination strategies in the definitive setting. Our hope is to summarize relevant literature in order to provide a foundation for interpreting emerging data and designing future trials to maximize care, both in disease control and patient quality of life.
Enhanced Therapeutic Effects of 177Lu-DOTA-M5A in Combination with Heat Shock Protein 90 Inhibitor Onalespib in Colorectal Cancer Xenografts
Authors: Mohajershojai Tabassom , Spangler Douglas , Chopra Saloni , Frejd Fredrik Y. , Yazaki Paul J. , Nestor Marika
Published: August 2023

Carcinoembryonic antigen (CEA) has emerged as an attractive target for theranostic applications in colorectal cancers (CRCs). In the present study, the humanized anti-CEA antibody hT84.66-M5A (M5A) was labeled with 177Lu for potential CRC therapy. Moreover, the novel combination of 177Lu-DOTA-M5A with the heat shock protein 90 inhibitor onalespib, suggested to mediate radiosensitizing properties, was assessed in vivo for the first time. M5A antibody uptake and therapeutic effects, alone or in combination with onalespib, were assessed in human CRC xenografts and visualized using SPECT/CT imaging. Although both 177Lu-DOTA-M5A and onalespib monotherapies effectively reduced tumor growth rates, the combination therapy demonstrated the most substantial impact, achieving a fourfold reduction in tumor growth compared to the control group. Median survival increased by 33% compared to 177Lu-DOTA-M5A alone, and tripled compared to control and onalespib groups. Importantly, combination therapy yielded comparable or superior effects to the double dose of 177Lu-DOTA-M5A monotherapy. 177Lu-DOTA-M5A increased apoptotic cell levels, indicating its potential to induce tumor cell death. These findings show promise for 177Lu-DOTA-M5A as a CRC therapeutic agent, and its combination with onalespib could significantly enhance treatment efficacy. Further in vivo studies are warranted to validate these findings fully and explore the treatment’s potential for clinical use.
Impact of Age at Diagnosis on Clinicopathological Features, Prognosis, and Management of Gastric Cancer: A Retrospective Single-Center Experience from Spain
Authors: Díaz del Arco Cristina , Ortega Medina Luis , Estrada Muñoz Lourdes , Molina Roldán Elena , García Gómez de las Heras Soledad , Fernández Aceñero María Jesús
Published: August 2023

The impact of age on various aspects of gastric cancer (GC) remains controversial. Clarifying this issue can improve our understanding of the disease, refine risk stratification models, and aid in personalized therapeutic approaches. This study aimed to evaluate the influence of age at diagnosis on the clinicopathological features, prognosis, and management of a specific cohort of Spanish patients with resected GC. The study encompassed 315 patients treated at a single tertiary hospital in Spain, divided into two age-based subgroups: ≤65 years and >65 years. The mean and median ages at diagnosis were 72 and 76 years. Most tumors were diagnosed at pT3 stage (49.2%), and 59.6% of patients had lymph node metastases. 21.3% of cases were diagnosed with GC at age ≤ 65 years. Younger patients showed a significantly higher prevalence of flat, diffuse, high-grade tumors, signet-ring cells, perineural infiltration, D2 lymphadenectomies, and adjuvant therapy. They also exhibited a higher rate of recurrences, but had a significantly longer follow-up. Kaplan-Meier curves indicated no significant prognostic differences based on age. Finally, age did not independently predict overall survival or disease-free survival. Our results suggest that younger patients may require more aggressive treatment due to adverse clinicopathologic features, but the lack of prognostic differences among age groups in our cohort indicates the need for further investigation into the complex interplay between age, clinicopathologic factors, and long-term outcomes in GC.
Clinico-Pathological Features, Outcomes and Impacts of COVID-19 Pandemic on Patients with Early-Onset Colorectal Cancer: A Single-Institution Experience
Authors: Martinez-Perez Daniel , Viñal David , Peña-Lopez Jesús , Jimenez-Bou Diego , Ruiz-Gutierrez Iciar , Martinez-Recio Sergio , Alameda-Guijarro María , Rueda-Lara Antonio , Martin-Montalvo Gema , Ghanem Ismael , Custodio Ana Belén , Trilla-Fuertes Lucia , Gamez-Pozo Angelo , Barbachano Antonio , Rodriguez-Cobos Javier , Bustamante-Madrid Pilar , Fernandez-Barral Asuncion , Burgos Aurora , Prieto-Nieto Maria Isabel , Pastrian Laura Guerra , González-Sancho José Manuel , Muñoz Alberto , Feliu Jaime , Rodríguez-Salas Nuria
Published: August 2023

Background: The rising incidence of colorectal cancer (CRC) among young patients is alarming. We aim to characterize the clinico-pathological features and outcomes of patients with early-onset CRC (EOCRC), as well as the impacts of COVID-19 pandemic. Methods: We included all patients with pathologically confirmed diagnoses of CRC at Hospital Universitario La Paz from October 2016 to December 2021. The EOCRC cut-off age was 50 years old. Results: A total of 1475 patients diagnosed with CRC were included, eighty (5.4%) of whom had EOCRC. Significant differences were found between EOCRC and later-onset patients regarding T, N stage and metastatic presentation at diagnosis; perineural invasion; tumor budding; high-grade tumors; and signet ring cell histology, with all issues having higher prevalence in the early-onset group. More EOCRC patients had the RAS/ BRAF wild type. Chemotherapy was administered more frequently to patients with EOCRC. In the metastatic setting, the EOCRC group presented a significantly longer median OS. Regarding the COVID-19 pandemic, more patients with COVID-19 were diagnosed with metastatic disease (61%) in the year after the lockdown (14 March 2020) than in the pre-pandemic EOCRC group (29%). Conclusions: EOCRC is diagnosed at a more advanced stage and with worse survival features in localized patients. More patients with EOCRC were diagnosed with metastatic disease in the year after the COVID-19 pandemic lockdown. The long-term consequences of COVID-19 are yet to be determined.
Immunotherapy for Colorectal Cancer with High Microsatellite Instability: The Ongoing Search for Biomarkers
Authors: Ros Javier , Baraibar Iosune , Saoudi Nadia , Rodriguez Marta , Salvà Francesc , Tabernero Josep , Élez Elena
Published: August 2023

Microsatellite instability (MSI) is a biological condition associated with inflamed tumors, high tumor mutational burden (TMB), and responses to immune checkpoint inhibitors. In colorectal cancer (CRC), MSI tumors are found in 5% of patients in the metastatic setting and 15% in early-stage disease. Following the impressive clinical activity of immune checkpoint inhibitors in the metastatic setting, associated with deep and long-lasting responses, the development of immune checkpoint inhibitors has expanded to early-stage disease. Several phase II trials have demonstrated a high rate of pathological complete responses, with some patients even spared from surgery. However, in both settings, not all patients respond and some responses are short, emphasizing the importance of the ongoing search for accurate biomarkers. While various biomarkers of response have been evaluated in the context of MSI CRC, including B2M and JAK1/2 mutations, TMB, WNT pathway mutations, and Lynch syndrome, with mixed results, liver metastases have been associated with a lack of activity in such strategies. To improve patient selection and treatment outcomes, further research is required to identify additional biomarkers and refine existing ones. This will allow for the development of personalized treatment approaches and the integration of novel therapeutic strategies for MSI CRC patients with liver metastases.
Advantages of the Combinatorial Molecular Targeted Therapy of Head and Neck Cancer—A Step before Anakoinosis-Based Personalized Treatment
Authors: Kleszcz Robert
Published: August 2023

The molecular initiators of Head and Heck Squamous Cell Carcinoma (HNSCC) are complex. Human Papillomavirus (HPV) infection is linked to an increasing number of HNSCC cases, but HPV-positive tumors generally have a good prognosis. External factors that promote the development of HPV-negative HNSCC include tobacco use, excessive alcohol consumption, and proinflammatory poor oral hygiene. On a molecular level, several events, including the well-known overexpression of epidermal growth factor receptors (EGFR) and related downstream signaling pathways, contribute to the development of HNSCC. Conventional chemotherapy is insufficient for many patients. Thus, molecular-based therapy for HNSCC offers patients a better chance at a cure. The first molecular target for therapy of HNSCC was EGFR, inhibited by monoclonal antibody cetuximab, but its use in monotherapy is insufficient and induces resistance. This article describes attempts at combinatorial molecular targeted therapy of HNSCC based on several molecular targets and exemplary drugs/drug candidates. The new concept of anakoinosis-based therapy, which means treatment that targets the intercellular and intracellular communication of cancer cells, is thought to be the way to improve the clinical outcome for HNSCC patients. The identification of a link between molecular targeted therapy and anakoinosis raises the potential for further progress in HPV-negative HNSCC therapy.
Single-Cell Transcriptomic Analysis Reveals the Molecular Profile of Go-Opsin Photoreceptor Cells in Sea Urchin Larvae
Authors: Cocurullo Maria , Paganos Periklis , Annunziata Rossella , Voronov Danila , Arnone Maria Ina
Published: August 2023

The ability to perceive and respond to light stimuli is fundamental not only for spatial vision but also to many other light-mediated interactions with the environment. In animals, light perception is performed by specific cells known as photoreceptors and, at molecular level, by a group of GPCRs known as opsins. Sea urchin larvae possess a group of photoreceptor cells (PRCs) deploying a Go-Opsin (Opsin3.2) which have been shown to share transcription factors and morphology with PRCs of the ciliary type, raising new questions related to how this sea urchin larva PRC is specified and whether it shares a common ancestor with ciliary PRCs or it if evolved independently through convergent evolution. To answer these questions, we combined immunohistochemistry and fluorescent in situ hybridization to investigate how the Opsin3.2 PRCs develop in the sea urchin Strongylocentrotus purpuratus larva. Subsequently, we applied single-cell transcriptomics to investigate the molecular signature of the Sp-Opsin3.2-expressing cells and show that they deploy an ancient regulatory program responsible for photoreceptors specification. Finally, we also discuss the possible functions of the Opsin3.2-positive cells based on their molecular fingerprint, and we suggest that they are involved in a variety of signaling pathways, including those entailing the thyrotropin-releasing hormone.
Stable Chinese Hamster Ovary Suspension Cell Lines Harboring Recombinant Human Cytochrome P450 Oxidoreductase and Human Cytochrome P450 Monooxygenases as Platform for In Vitro Biotransformation Studies
Authors: Schulz Christian , Herzog Natalie , Kubick Stefan , Jung Friedrich , Küpper Jan-Heiner
Published: August 2023

In the liver, phase-1 biotransformation of drugs and other xenobiotics is largely facilitated by enzyme complexes consisting of cytochrome P450 oxidoreductase (CPR) and cytochrome P450 monooxygenases (CYPs). Generated from human liver-derived cell lines, recombinant in vitro cell systems with overexpression of defined phase-1 enzymes are widely used for pharmacological and toxicological drug assessment and laboratory-scale production of drug-specific reference metabolites. Most, if not all, of these cell lines, however, display some background activity of several CYPs, making it difficult to attribute effects to defined CYPs. The aim of this study was to generate cell lines with stable overexpression of human phase-1 enzymes based on Chinese hamster ovary (CHO) suspension cells. Cells were sequentially modified with cDNAs for human CPR in combination with CYP1A2, CYP2B6, or CYP3A4, using lentiviral gene transfer. In parallel, CYP-overexpressing cell lines without recombinant CPR were generated. Successful recombinant expression was demonstrated by mRNA and protein analyses. Using prototypical CYP-substrates, generated cell lines proved to display specific enzyme activities of each overexpressed CYP while we did not find any endogenous activity of those CYPs in parental CHO cells. Interestingly, cell lines revealed some evidence that the dependence of CYP activity on CPR could vary between CYPs. This needs to be confirmed in further studies. Recombinant expression of CPR was also shown to enhance CYP3A4-independent metabolisation of testosterone to androstenedione in CHO cells. We propose the novel serum-free CHO suspension cell lines with enhanced CPR and/or defined CYP activity as a promising “humanised” in vitro model to study the specific effects of those human CYPs. This could be relevant for toxicology and/or pharmacology studies in the pharmaceutical industry or medicine.
The Highs and Lows of FBXW7: New Insights into Substrate Affinity in Disease and Development
Authors: de la Cova Claire C.
Published: August 2023

FBXW7 is a critical regulator of cell cycle, cell signaling, and development. A highly conserved F-box protein and component of the SKP1–Cullin–F-box (SCF) complex, FBXW7 functions as a recognition subunit within a Cullin–RING E3 ubiquitin ligase responsible for ubiquitinating substrate proteins and targeting them for proteasome-mediated degradation. In human cells, FBXW7 promotes degradation of a large number of substrate proteins, including many that impact disease, such as NOTCH1, Cyclin E, MYC, and BRAF. A central focus for investigation has been to understand the molecular mechanisms that allow the exquisite substrate specificity exhibited by FBXW7. Recent work has produced a clearer understanding of how FBXW7 physically interacts with both high-affinity and low-affinity substrates. We review new findings that provide insights into the consequences of “hotspot” missense mutations of FBXW7 that are found in human cancers. Finally, we discuss how the FBXW7–substrate interaction, and the kinases responsible for substrate phosphorylation, contribute to patterned protein degradation in C. elegans development.
34th Annual Meeting of the Society for Light Treatment and Biological Rhythms (SLTBR), 30 May–1 June, Lausanne, Switzerland
Authors: Cajochen Christian
Published: August 2023

The Society for Light Treatment and Biological Rhythms (SLTBR) held this year’s annual meeting at the Ecole Polytechnique Fédérale (EPFL) in Lausanne, Switzerland from 30 May to 1 June in conjunction with the Day Light Academy (DLA) [...]
Crack-Free Copper Alloy Coating on Aluminum Alloy Fabricated by Laser Cladding
Authors: Jin Yajuan , Lu Baochun , Tang Xudong
Published: August 2023

Crack-free Cu alloy coating has been fabricated on Al alloy substrate with the existence of a Ag buffer layer. The Cu alloy coating had 12 at.% Al and 45 at.% Ag, which contributed to the formation of Cu solid solution and the eutectic phase (transformation temperature 780 °C). The eutectic phase was characterized as finer Cu solid solution and finer Ag solid solution. The Ag buffer layer had the main contents of Ag2Al and Ag solid solution, and it not only hindered the formation of brittle intermetallic compounds (IMCs)but also reduced the thermal stress as its intermediate coefficient of thermal expansion (CTE). Furthermore, the plastic deformation of Ag solid solution in the Ag buffer layer and Cu solid solution in Cu alloy coating also relieved the thermal stress which was generated during the cladding process. All these three aspects inhibited crack generation. And the hardness of the Cu alloy coating increased to approximately 275 HV due to the strengthening effect of Al solid solution, grain boundary within the finer eutectic phase, and nano twin in the Cu solid solution of the eutectic phase.
The Polishing of Inner Wall on Medical Device Hole by Shear Thickening Abrasive Flow
Authors: Ye Biqing , Mao Wenbin , Ji Renquan , Zeng Xi , Zhang Li
Published: August 2023

To improve medical device hole inner wall quality and overcome issues of traditional abrasive flow methods—limited fluidity in small holes causing deformation due to high inner wall pressure, and slow processing with low viscosity abrasives—a new method called shear thickening abrasive flow polishing is suggested. It uses shear thickening fluid as the medium. By leveraging the Preston equation and fluid dynamics theory, this study establishes both an abrasive flow dynamics model and a material removal model for the shear thickening abrasive flow machining of small titanium alloy hole workpieces in medical instruments. Utilizing the COMSOL software, the flow field state of shear thickening fluid within small holes is examined under varying flow behavior indexes and flow velocities. The findings demonstrate that shear thickening fluid yields superior polishing effects compared to Newtonian fluid. Elevating the flow behavior indexes facilitates a higher material removal rate on the inner wall surface; however, excessively large flow behavior indexes diminish the uniformity of material removal, thereby hindering the attainment of a high-quality polished surface. Furthermore, excessively large flow behavior indexes can reduce fluidity and consequently lower the efficiency of the polishing process. Conversely, while maintaining a constant flow behavior index, increasing the flow velocity contributes to an enhanced material removal rate and improved polishing efficiency. Nevertheless, as the flow velocity rises, the uniformity of inner wall surface roughness diminishes, posing challenges in achieving a high-quality polished surface.
Development and Performance Evaluation of Stretchable Silver Pastes for Screen Printing on Thermoplastic Polyurethane Films
Authors: Nam Hyun J. , Hwangbo Yu H. , Nam Su Y. , Nam Hyun M.
Published: August 2023

Efficient, stretchable wiring electrodes are achieved when the resistance change during expansion and contraction is minimal. Herein, we prepared silver pastes specifically designed for screen printing on thermoplastic polyurethane films; they exhibit minimal resistance changes. The pastes were prepared using silver particles with sizes of 2 and 7 μm as well as a mixture of 2 and 7 μm silver particles (50:50 wt%). These pastes were analyzed using methods such as rheological measurements, thermogravimetric analysis, printability tests, tensile and torsion tests, and light-emitting diode (LED) tests. The most promising results were obtained when exclusively using 2 μm silver flake particles. The pastes demonstrated a viscosity of 24,880 cps, a thixotropic index value of 2.82, excellent printability, and consistent resistance measurements even after 100% stretch, thus indicating exceptional tensile properties. Moreover, the pastes exhibited substantial stability, with no change in brightness after the attachment of seven LEDs at 20% tension.
Digital Competence of Higher Education Teachers at a Distance Learning University in Portugal
Authors: Moreira José António , Nunes Catarina S. , Casanova Diogo
Published: August 2023

The Digital Education Action Plan (2021–2027) launched by the European Commission aims to revolutionize education systems, prioritizing the development of a robust digital education ecosystem and the enhancement of teachers’ digital transformation skills. This study focuses on Universidade Aberta, Portugal, to identify the strengths and weaknesses of teachers’ digital skills within the Digital Competence Framework for Educators (DigCompEdu). Using a quantitative approach, the research utilized the DigCompEdu CheckIn self-assessment questionnaire, validated for the Portuguese population, to evaluate teachers’ perceptions of their digital competences. A total of 118 teachers participated in the assessment. Findings revealed that the teachers exhibited a notably high overall level of digital competence, positioned at the intersection of B2 (Expert) and C1 (Leader) on the DigCompEdu scale. However, specific areas for improvement were identified, particularly in Digital Technologies Resources and Assessment, the core pedagogical components of DigCompEdu, which displayed comparatively lower proficiency levels. To ensure continuous progress and alignment with the Digital Education Action Plan’s strategic priorities, targeted teacher training initiatives should focus on enhancing competences related to Digital Technologies Resources and Assessment.
Characterising the Educational Experiences and Mental Health of Children with Pre-Existing Learning Difficulty or Specific Learning Disorder (SLD) during the COVID-19 Pandemic
Authors: Catroppa Cathy , Morrison Elle , Ryan Nicholas P. , Khan Noor , Botchway-Commey Edith N. , Moe Stella , Piazza Chandelle , Corso Kaitlyn , Rae Gabriel , Bull Catherine , McIntosh Emma , Anderson Vicki , Crowe Louise , Stonier-Kipen Claire , Sood Nikita Tuli
Published: August 2023

This prospective study sought to characterise the educational experiences, mental health, and behavioural functioning of Australian children with a pre-existing learning difficulty or specific learning disorder (SLD) during the COVID-19 pandemic. The study also evaluated the potential role of parent psychological distress as a risk factor for poorer child functioning in this high-risk population. Using a prospective longitudinal design, the study involved 58 parents of children and adolescents with a pre-existing learning difficulty or specific learning disorder (M age = 11.9 years; range 7–17 years) who were initially referred to a state-wide diagnostic centre for specific learning disorders in Melbourne, Victoria, Australia. Child outcomes were assessed using the COVID-19 Wellbeing and Mental Health Survey (a modified version of the CoRonavIruS Health Impact Survey [CRISIS] tool), the Strengths and Difficulties Questionnaire (SDQ), and the Emotional Distress Scale from the Patient-Reported Outcomes Measurement Information System (PROMIS). Parents’ mental health was assessed using the CRISIS tool and the Kessler Psychological Distress Scale (K10). In keeping with initial predictions, a large proportion of parents expressed significant disruption to child educational experience and routines, including challenges related to child engagement in remote learning platforms during COVID-19. Compared to pre-pandemic mental health symptom ratings, children experienced significantly higher symptoms of worry, negative thoughts, loneliness, agitation, and aggression during the pandemic period (all p < 0.05). As expected, higher levels of parent distress predicted greater child worry symptoms (p = 0.003) and more frequent child behavioural difficulties (p = 0.004). These results help elucidate the specific psychological and educational challenges faced by children with pre-existing learning difficulty or SLD during the COVID-19 pandemic. Family-centred intervention and/or supports may help to address the unique educational and psychological needs of young people with pre-existing learning differences and their families during future global pandemics.
Female Higher Education Students’ Lived Experiences during the COVID-19 Pandemic: The Case Study Viewed through a Phenomenological Lens
Authors: Atkins Denise , Godber Kathleen
Published: August 2023

This paper examines the subjective realities of female students in higher education as they navigated their well-being and active lives during the COVID-19 pandemic. Drawing upon Merleau-Ponty’s phenomenological framework, which confronts an often-neglected dimension of our experience—the lived body and the phenomenal world—we aim to inform the development of targeted support and interventions to address the specific needs of female students, in future pandemic times. By exploring how three female students studying sport and recreation in higher education perceived their experiences, this article seeks to shed light on the unique challenges faced by these women in maintaining physical activity, coping with isolation and a change in social networks, and managing their mental health in the context of the pandemic. Understanding these subjective realities (such as isolation, restricted physical activity, and loss of social connections) and interpreting the three students’ lived habitats, their bodily responsiveness, and their spontaneity ensures that their experience is heard, and appropriate future support can be given.
Coordinative Unsaturation in an Antimony(III)-Complex with the 2-Salicylidenaminophenolato Ligand: Synthesis, Crystal Structure, Spectroscopic Analysis, and DFT Studies
Authors: Knerr Steven , Böhme Uwe , Herbig Marcus
Published: August 2023

In this work, the synthesis and structure of an antimony complex with an aromatic, asymmetric tridentate ligand without an Sb-C bond were studied. Ethoxy(2-salicylidenaminophenolato)antimony(III) was studied with NMR, UV-Vis, and IR spectroscopy and the molecular structure was determined by single crystal X-ray diffraction. The antimony atom is formally tetracoordinate in this molecule. Coordinative unsaturation becomes visible in the solid-state structure where intermolecular Sb…O interactions supplement the coordination sphere of the antimony atom to be hexacoordinated. Quantum chemical calculations were performed in order to obtain a better understanding of the bond properties in the antimony complex. These show a spherical distribution of the lone pair at antimony and polar shared bonds from antimony to the heteroatoms of the tridentate ligand.
Diagnostic Approaches to Adult-Type Diffuse Glial Tumors: Comparative Literature and Clinical Practice Study
Authors: Veikutis Vincentas , Brazdziunas Mindaugas , Keleras Evaldas , Basevicius Algidas , Grib Andrei , Skaudickas Darijus , Lukosevicius Saulius
Published: August 2023

Gliomas are the most frequent intrinsic central nervous system tumors. The new 2021 WHO Classification of Central Nervous System Tumors brought significant changes into the classification of gliomas, that underline the role of molecular diagnostics, with the adult-type diffuse glial tumors now identified primarily by their biomarkers rather than histology. The status of the isocitrate dehydrogenase (IDH) 1 or 2 describes tumors at their molecular level and together with the presence or absence of 1p/19q codeletion are the most important biomarkers used for the classification of adult-type diffuse glial tumors. In recent years terminology has also changed. IDH-mutant, as previously known, is diagnostically used as astrocytoma and IDH-wildtype is used as glioblastoma. A comprehensive understanding of these tumors not only gives patients a more proper treatment and better prognosis but also highlights new difficulties. MR imaging is of the utmost importance for diagnosing and supervising the response to treatment. By monitoring the tumor on followup exams better results can be achieved. Correlations are seen between tumor diagnostic and clinical manifestation and surgical administration, followup care, oncologic treatment, and outcomes. Minimal resection site use of functional imaging (fMRI) and diffusion tensor imaging (DTI) have become indispensable tools in invasive treatment. Perfusion imaging provides insightful information about the vascularity of the tumor, spectroscopy shows metabolic activity, and nuclear medicine imaging displays tumor metabolism. To accommodate better treatment the differentiation of pseudoprogression, pseudoresponse, or radiation necrosis is needed. In this report, we present a literature review of diagnostics of gliomas, the differences in their imaging features, and our radiology’s departments accumulated experience concerning gliomas.