bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Roles of CD36 in Regulating Muscle Insulin Response Depend on Palmitic Acid Load
Authors: Sun Jingyu , Su Yajuan , Chen Jiajia , Qin Duran , Xu Yaning , Chu Hang , Lu Tianfeng , Dong Jingmei , Qin Lili , Li Weida
Published: February 2023

The possible role of fatty acid translocase (CD36) in the treatment of obesity has gained increasing research interest since researchers recognized its coordinated function in fatty acid uptake and oxidation. However, the effect of CD36 deficiency on intracellular insulin signaling is complex and its impact may depend on different nutritional stresses. Therefore, we investigated the various effects of CD36 deletion on insulin signaling in C2C12 myotubes with or without palmitic acid (PA) overload. In the present work, we reported the upregulated expression levels of CD36 in the skeletal muscle tissues of obese humans and mice as well as in C2C12 myotubes with PA stimulation. CD36 knockdown using RNA interference showed that insulin signaling was impaired in CD36-deficient C2C12 cells in the absence of PA loading, suggesting that CD36 is essential for the maintenance of insulin action, possibly resulting from increased mitochondrial dysfunction and endoplasmic reticulum (ER) stress; however, CD36 deletion improved insulin signaling in the presence of PA overload due to a reduction in lipid overaccumulation. In conclusion, we identified differential roles of CD36 in regulating muscle insulin response under conditions with and without PA overload, which provides supportive evidence for further research into therapeutic approaches to diabetes.
A Retrospective Study on the Role of Metformin in Colorectal Cancer Liver Metastases
Authors: Rada Miran , Krzywon Lucyna , Petrillo Stephanie , Lazaris Anthoula , Metrakos Peter
Published: February 2023

Colorectal cancer liver metastases (CRCLMs) have two main histopathological growth patterns (HPGs): desmoplastic (DHGP) and replacement (RHGP). The vascularization in DHGP tumours is angiogenic, while the RHGP tumours exert vessel co-option vasculature. The presence of vessel co-option tumours is associated with poor response to anti-angiogenic agents and chemotherapy, as well as a worse prognosis. Metformin has been shown to influence the progression and vasculature of tumours in different cancers. However, its role in CRCLM is poorly understood. Herein, we conducted a retrospective cohort study to examine the role of metformin in CRCLM. A dataset of 108 patients was screened, of which 20 patients used metformin. The metformin user patients did not use metformin as an anticancer agent. We noticed a significantly lower percentage of CRCLM patients with vessel co-opting RHGP tumours in the population that used metformin compared to CRCLM patients who did not use metformin. Similar results were obtained when we compared the ratio of recurrence and extrahepatic metastases incidence. Moreover, the metformin user patients had significantly higher survival outcome compared to nonusers. Collectively, our data suggest that metformin administration is likely associated with better prognosis of CRCLM.
Metal–Organic Frameworks (MOFs) and Their Composites as Emerging Biomaterials for Osteoarthritis Treatment
Authors: Wong Hoi-Lam , Tsang Chung-Yin , Beyer Sebastian
Published: February 2023

Metal-Organic Frameworks (MOFs) have emerged as a novel component in biomaterial formulations over the past 5 years. The bioactivity of MOFs in bone or cartilage tissue is mediated through the sustained delivery of metal ions, bioactive ligands, or drug molecules that are loaded into the porous MOF structures. Alternatively, bioactivity may also originate from structure-specific properties. The latter includes the availability and accessibility of open metal coordination sites for the catalytic conversion of biomolecules into active agents. This narrative highlight aims to inspire strategies to utilize MOFs for treating osteoarthritis (OA), with a special focus on augmenting hydrogel-based biomaterials with MOFs. The added value of MOFs in these hydrogel formulations is discussed, and the biological efficacy is compared to approaches applying classical injectable biomaterials for OA treatment. Possible future directions and pitfalls of these novel MOF–hydrogel composites are emphasized to assist future transition of MOFs into clinical applications.
Smart Biomechanical Adaptation Revealed by the Structure of Ostrich Limb Bones
Authors: Conti Simone , Sala Giuseppe , Mateus Octavio
Published: February 2023

Ostriches are known to be the fastest bipedal animal alive; to accomplish such an achievement, their anatomy evolved to sustain the stresses imposed by running at such velocities. Ostriches represent an excellent case study due to the fact that their locomotor kinematics have been extensively studied for their running capabilities. The shape and structure of ostrich bones are also known to be optimized to sustain the stresses imposed by the body mass and accelerations to which the bones are subjected during movements. This study focuses on the limb bones, investigating the structure of the bones as well as the material properties, and how both the structure and material evolved to maximise the performance while minimising the stresses applied to the bones themselves. The femoral shaft is hollowed and it presents an imbricate structure of fused bone ridges connected to the walls of the marrow cavity, while the tibial shaft is subdivided into regions having different mechanical characteristics. These adaptations indicate the optimization of both the structure and the material to bear the stresses. The regionalization of the material highlighted by the mechanical tests represents the capability of the bone to adapt to external stimuli during the life of an individual, optimizing not only the structure of the bone but the material itself.
The Influence of Electrode Design on Detecting the Effects of Ferric Ammonium Citrate (FAC) on Pre-Osteoblast through Electrical Cell-Substrate Impedance Sensing (ECIS)
Authors: Zhang Zheyuan , Yuan Xichen , Guo Huijie , Shang Peng
Published: February 2023

Detection sensitivity is a crucial factor in the application of ECIS sensors. For these biosensors, the electrode configuration has a direct impact on sensitivity, yet few studies on monopolar electrodes have been reported. In this study, ECIS sensor arrays, which have a series of working electrode configuration with a wide diameter range and different electrode number, were fabricated to monitor living osteoblast-like MC3T3-E1 cells. The experimental results revealed that when the electrode diameter was larger than 25 μm, electrodes with smaller diameter and number yielded higher impedance values and generated more impedance shift to cell status change. The membrane capacitance obtained by equivalent circuit fitting was at the same level. When the electrode diameter was even smaller, the results in detection of cell monolayer were opposite, and there was no distinct relationship between impedance and membrane capacitance shift to cell status change and electrode geometry. The proposed sensor chip, allowing for a sustained and stable detection of cellular impedance, provides the basis for the selection of the electrode configuration of monopolar electrodes. The test results of electrodes with a diameter of 25 μm and lower indicated the possibility of single cell impedance measurement, which can provide unique insight into the heterogeneous electrical behavior of cells, and, in this case, the electrode size should be close to the cell size.
Toward the Commercialization of Carbon Nanotube Field Effect Transistor Biosensors
Authors: Li Zhongyu , Xiao Mengmeng , Jin Chuanhong , Zhang Zhiyong
Published: February 2023

The development of biosensors based on field-effect transistors (FETs) using atomically thick carbon nanotubes (CNTs) as a channel material has the potential to revolutionize the related field due to their small size, high sensitivity, label-free detection, and real-time monitoring capabilities. Despite extensive research efforts to improve the sensitivity, selectivity, and practicality of CNT FET-based biosensors, their commercialization has not yet been achieved due to the non-uniform and unstable device performance, difficulties in their fabrication, the immaturity of sensor packaging processes, and a lack of reliable modification methods. This review article focuses on the practical applications of CNT-based FET biosensors for the detection of ultra-low concentrations of biologically relevant molecules. We discuss the various factors that affect the sensors’ performance in terms of materials, device architecture, and sensor packaging, highlighting the need for a robust commercial process that prioritizes product performance. Additionally, we review recent advances in the application of CNT FET biosensors for the ultra-sensitive detection of various biomarkers. Finally, we examine the key obstacles that currently hinder the large-scale deployment of these biosensors, aiming to identify the challenges that must be addressed for the future industrialization of CNT FET sensors.
A Minireview for Recent Development of Nanomaterial-Based Detection of Antibiotics
Authors: Hong Jiafu , Su Mengxing , Zhao Kunmeng , Zhou Yihui , Wang Jingjing , Zhou Shu-Feng , Lin Xuexia
Published: February 2023

Antibiotics are considered a new type of organic pollutant. Antibiotic residues have become a global issue due to their harm to human health. As the use of antibiotics is increasing in human life, such as in medicine, crops, livestock, and even drinking water, the accurate analysis of antibiotics is very vital. In order to develop rapid and on-site approaches for the detection of antibiotics and the analysis of trace-level residual antibiotics, a high-sensitivity, simple, and portable solution is required. Meanwhile, the rapid nanotechnology development of a variety of nanomaterials has been achieved. In this review, nanomaterial-based techniques for antibiotic detection are discussed, and some reports that have employed combined nanomaterials with optical techniques or electrochemical techniques are highlighted.
Application of Antipsychotic Drugs in Mood Disorders
Authors: Rybakowski Janusz K.
Published: February 2023

Since their first application in psychiatry seventy years ago, antipsychotic drugs, besides schizophrenia, have been widely used in the treatment of mood disorders. Such an application of antipsychotics is the subject of this narrative review. Antipsychotic drugs can be arbitrarily classified into three generations. First-generation antipsychotics (FGAs), such as phenothiazines and haloperidol, were mainly applied for the treatment of acute mania, as well as psychotic depression when combined with antidepressants. The second-generation, so-called atypical antipsychotics (SGAs), such as clozapine, risperidone, olanzapine, and quetiapine, have antimanic activity and are also effective for the maintenance treatment of bipolar disorder. Additionally, quetiapine exerts therapeutic action in bipolar depression. Third-generation antipsychotics (TGAs) started with aripiprazole, a partial dopamine D2 receptor agonist, followed by brexpiprazole, lurasidone, cariprazine, and lumateperone. Out of these drugs, aripiprazole and cariprazine have antimanic activity, lurasidone, cariprazine, and lumateperone exert a significant antidepressant effect on bipolar depression, while there is evidence for the efficacy of aripiprazole and lurasidone in the prevention of recurrence in bipolar disorder. Therefore, successive generations of antipsychotic drugs present a diverse spectrum for application in mood disorders. Such a pharmacological overlap in the treatment of schizophrenia and bipolar illness stands in contrast to the dichotomous Kraepelinian division of schizophrenia and mood disorders.
How Different Preparation Techniques Affect MRI-Induced Anxiety of MRI Patients: A Preliminary Study
Authors: Hamd Zuhal Y. , Alorainy Amal I. , Alrujaee Lena A. , Alshdayed Maha Y. , Wdaani Afrah M. , Alsubaie Atheer S. , Binjardan Layal A. , Kariri Sarab S. , Alaskari Rawan A. , Alsaeed Marah M. , Alharbi Mohammed Awad , Alotaibi Marzouk Sari. , Elhussein Nagwan , Khandaker Mayeen Uddin
Published: February 2023

Background: Magnetic resonance imaging (MRI) exams may cause patients to feel anxious before or during the scan, which affects the scanning outcome and leads to motion artifacts. Adequate preparation can effectively alleviate patients’ anxiety before the scan. We aimed to assess the effect of different preparation methods on MRI-induced anxiety: We conducted a prospective randomized study on MRI patients between March and May 2022. We divided 30 patients into two groups: the control group, which received routine preparation (RP), and the experimental group, which received video preparation (VP). We used the State-Trait Anxiety Inventory (STAI) to measure anxiety levels before and after the interventions. We assessed patients’ self-satisfaction after the scan: After preparation, VP (STAI mean = 10.7500) and RP (STAI mean = 12.7857), we observed a significant association between the pre- and post-STAI results in VP (p = 0.025). The effects of both methods in decreasing anxiety were more significant for first-timers (p = 0.009 in RP/0.014 in VP). We noted high satisfaction levels for both forms of preparation. The VP technique was superior in reducing patient anxiety, especially in first-time MRI patients. Hence, VP techniques can be used in different clinical settings to reduce anxiety and facilitate patients’ understanding of the instructions given.
Verification of the Four-Stage Model of Humor Processing: Evidence from an fMRI Study by Three-Element Verbal Jokes
Authors: Chang Chia-Yueh , Chan Yu-Chen , Chen Hsueh-Chih
Published: February 2023

The four-stage model comprises the expectation, incongruity, resolution, and elaboration stages of humor processing. In previous studies, most researchers used two-element jokes (setup and punch line) as stimuli, based on experimental methods, to explore the humor process. By contrast, the present study used a humor corpus with the novelty of three-element verbal jokes to perform direct separation from the material and clarify the humor processes. In this study, we used three-element verbal jokes and nonjokes, and we conducted a repeated-measures analysis of variance with a 3 × 2 two-way within-subject design. In humor processing, the posterior insula and middle frontal gyrus were mainly activated in the expectation; the middle temporal gyrus and the medial frontal gyrus in the incongruity; the inferior frontal gyri, superior frontal gyrus, and inferior parietal lobule in the resolution; and the ventromedial prefrontal cortex, amygdala, anterior insula, nucleus accumbens, and midbrain in the elaboration. The contributions of this study lie in its use of a humor corpus with the novelty of self-compiled three-element jokes, which not only successfully verified the models established in previous studies but added the expectation to the model; thus, this study separated the expectation and incongruity processes, making humor processing more complete.
TMS-Induced Modulation of EEG Functional Connectivity Is Affected by the E-Field Orientation
Authors: Pieramico Giulia , Guidotti Roberto , Nieminen Aino E. , D’Andrea Antea , Basti Alessio , Souza Victor H. , Nieminen Jaakko O. , Lioumis Pantelis , Ilmoniemi Risto J. , Romani Gian Luca , Pizzella Vittorio , Marzetti Laura
Published: February 2023

Coregistration of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) allows non-invasive probing of brain circuits: TMS induces brain activation due to the generation of a properly oriented focused electric field (E-field) using a coil placed on a selected position over the scalp, while EEG captures the effects of the stimulation on brain electrical activity. Moreover, the combination of these techniques allows the investigation of several brain properties, including brain functional connectivity. The choice of E-field parameters, such as intensity, orientation, and position, is crucial for eliciting cortex-specific effects. Here, we evaluated whether and how the spatial pattern, i.e., topography and strength of functional connectivity, is modulated by the stimulus orientation. We systematically altered the E-field orientation when stimulating the left pre-supplementary motor area and showed an increase of functional connectivity in areas associated with the primary motor cortex and an E-field orientation-specific modulation of functional connectivity intensity.
Effects of Combined Intervention of rTMS and Neurotransmitter Drugs on the Brain Functional Networks in Patients with Cognitive Impairment
Authors: Li Mengyun , Qin Zhiming , Chen Haifeng , Yang Zhiyuan , Wang Lianlian , Qin Ruomeng , Zhao Hui , Bai Feng
Published: February 2023

Alzheimer’s disease (AD) causes extensive neural network dysfunction. Memantine and donepezil are commonly used as monotherapy or in combination with non-drug interventions, such as repetitive transcranial magnetic stimulation (rTMS), for its treatment. However, no studies have reported any differences between the effects of combined neurotransmitter and rTMS interventions versus rTMS alone on the brain networks of patients with cognitive impairment. Therefore, it is crucial to explore the advantages of different intervention methods to guide clinical practice. We used resting-state functional magnetic resonance imaging (rs-fMRI) to investigate the impact of neurotransmitter superimposed rTMS and rTMS alone on the brain functional network of patients with cognitive impairment. We divided patients with cognitive impairment who had received rTMS into two groups based on whether they received neurotransmitters: the combined intervention group and the rTMS-alone intervention group. We conducted rs-fMRI scans and comprehensively assessed cognitive function in these patients. To examine the effects of the superimposed interventions, we utilized independent component analysis to evaluate the functional connectivity of brain networks in these patients. Compared to the rTMS-alone intervention group, co-intervention of neurotransmitter drugs and rTMS exhibited potential for cognitive enhancement via the reconstructed inter-network connectivity of the cerebellum and the enhanced intra-network connectivity of the frontal-parietal regions in these patients with cognitive impairment. We hypothesized that the combination of neurotransmitter drugs and rTMS intervention could have greater clinical benefits than rTMS intervention alone, leading to improved cognitive function in patients with cognitive impairment.
Challenges in Understanding Numerical Learning: Editorial for Brain Sciences Special Issue “Neurocognitive Signatures of Math (Learning) across the Lifespan and Their Interrelation with Other Aspects of Cognition and Emotion”
Authors: Klein Elise , Zamarian Laura , Kaufmann Liane
Published: February 2023

Living in our information- and technology-driven society at the beginning of the 21st century requires the ability to understand and handle numbers not only for a successful career but also for coping with everyday life tasks [...]
Risk of Motor Vehicle Collisions and Culpability among Older Drivers Using Cannabis: A Meta-Analysis
Authors: Chinna-Meyyappan Arun , Wang Hui Jue , Bawa Kritleen K. , Ellazar Edward , Norris-Roozmon Emilie , Naglie Gary , Herrmann Nathan , Charlton Judith L. , Koppel Sjaan , Castel Saulo , Lanctôt Krista L. , Rapoport Mark J.
Published: February 2023

Limited studies have investigated the effects of cannabis use on driving among older adults, who represent the fastest growing segment of drivers globally. We conducted a systematic review and meta-analysis to evaluate the effects of delta-9-tetrahydrocannabinol (THC) exposure on risks of (1) motor vehicle collisions (MVC) and (2) culpability for MVCs among adults 50 years and older. Three reviewers screened 7022 studies identified through MEDLINE, EMBASE, CENTRAL, and PsycINFO. Odds Ratios (OR) were calculated using the Mantel-Haenszel method in Review Manager 5.4.1. Heterogeneity was assessed using I2. The National Heart, Lung, and Blood Institute tool was used to assess the quality of each study. Seven cross-sectional studies were included. Three studies evaluated culpability while four evaluated MVC. The pooled risk of MVC was not significantly different between THC-positive and THC-negative older drivers (OR, 95% CI 1.15 [0.40, 3.31]; I2 = 72%). In culpability studies, THC exposure was not significantly associated with an increased risk of being culpable for MVC among adults over the age of 50 (OR, 95% CI 1.24 [0.95, 1.61]; I2 = 0%). Inspection of funnel plots did not indicate publication bias. Our review found that THC exposure was not associated with MVC involvement nor with culpability for MVCs.
Associations between Symptom Severity of Autism Spectrum Disorder and Screen Time among Toddlers Aged 16 to 36 Months
Authors: Sadeghi Saeid , Pouretemad Hamid Reza , Badv Reza Shervin , Brand Serge
Published: February 2023

There is growing evidence that prevalence rates of autism spectrum disorder (ASD) are increasing. A number of factors appear to contribute to this increase, including excessive screen time. Screen time seems to be linked to the severity of the symptoms of ASD. Given this, the aim of the present cross-sectional study was to investigate the association between early screen time and ASD symptoms severity in the first 36 months of life. To this end, sixty-eight Iranian toddlers (mean age: 27.09 months; 22.1% females) with ASD were recruited. Parents completed the modified checklist for autism in toddlers (M-CHAT), the Repetitive Behavior Scale-Revised (RBS-R), and a lifestyle checklist. Next, parents rated children’s daily exposure to content specifically designed (foreground media) and not specifically designed (background media) for children, along with their daily exposure to social interaction. Per day, toddlers spent 5.12 h (±3.77) with foreground media, 3.72 h (±3.57) with background media, and 2.89 h (±2.74) in interaction with other people (parents). To test the hypotheses, we performed a series of Pearson’s correlations and multiple regression analyses. Toddlers’ higher severity scores for ASD symptoms were associated with longer foreground (r = 0.234, p = 0.001) and longer background (r = 0.180, p = 0.012) media duration, and with shorter duration of interaction with others (r = 0.192, p = 0.009). Toddlers spending 1 h more in foreground screen time and background screen time have 0.38 and 0.29 more units in the ASD symptom severity scale, respectively, while toddlers spending 1 h more in social interactions have 0.42 fewer units in the ASD symptom severity scale. The screen time and interaction duration are related to ASD symptoms severity of toddlers. The cross-sectional study design precludes causal associations, although bi-directional relationships appear plausible.
Intelligent and Computer Technologies’ Application in Construction
Authors: Guo Hongling , Lin Jia-Rui , Yu Yantao
Published: February 2023

The construction industry is faced with many challenges, such as lagging productivity [...]
COVID-19 Severity and Survival over Time in Patients with Hematologic Malignancies: A Population-Based Registry Study
Authors: Martínez-López Joaquín , De la Cruz Javier , Gil-Manso Rodrigo , Alegre Adrián , Ortiz Javier , Llamas Pilar , Martínez Yolanda , Hernández-Rivas José-Ángel , González-Gascón Isabel , Benavente Celina , Estival Monteliu Pablo , Jiménez-Yuste Víctor , Canales Miguel , Bastos Mariana , Kwon Mi , Valenciano Susana , Callejas-Charavia Marta , López-Jiménez Javier , Herrera Pilar , Duarte Rafael , Núñez Martín-Buitrago Lucía , Sanchez Godoy Pedro , Jacome Yerovi Cristina , Martínez-Barranco Pilar , García Roa María , Escolano Escobar Cristian , Matilla Arturo , Rosado Sierra Belén , Aláez-Usón María Concepción , Quiroz-Cervantes Keina , Martínez-Chamorro Carmen , Pérez-Oteyza Jaime , Martos-Martinez Rafael , Herráez Regina , González-Santillana Clara , Del Campo Juan Francisco , Alonso Arancha , de la Fuente Adolfo , Pascual Adriana , Bustelos-Rodriguez Rosalía , Sebrango Ana , Ruiz Elena , Marcheco-Pupo Eriel Alexis , Grande Carlos , Cedillo Ángel , Lumbreras Carlos , Arroyo Barea Andrés , Casas-Rojo José Manuel , Calbacho Maria , Diez-Martín José Luis , García-Suárez Julio
Published: February 2023

Mortality rates for COVID-19 have declined over time in the general population, but data in patients with hematologic malignancies are contradictory. We identified independent prognostic factors for COVID-19 severity and survival in unvaccinated patients with hematologic malignancies, compared mortality rates over time and versus non-cancer inpatients, and investigated post COVID-19 condition. Data were analyzed from 1166 consecutive, eligible patients with hematologic malignancies from the population-based HEMATO-MADRID registry, Spain, with COVID-19 prior to vaccination roll-out, stratified into early (February–June 2020; n = 769 (66%)) and later (July 2020–February 2021; n = 397 (34%)) cohorts. Propensity-score matched non-cancer patients were identified from the SEMI-COVID registry. A lower proportion of patients were hospitalized in the later waves (54.2%) compared to the earlier (88.6%), OR 0.15, 95%CI 0.11–0.20. The proportion of hospitalized patients admitted to the ICU was higher in the later cohort (103/215, 47.9%) compared with the early cohort (170/681, 25.0%, 2.77; 2.01–3.82). The reduced 30-day mortality between early and later cohorts of non-cancer inpatients (29.6% vs. 12.6%, OR 0.34; 0.22–0.53) was not paralleled in inpatients with hematologic malignancies (32.3% vs. 34.8%, OR 1.12; 0.81–1.5). Among evaluable patients, 27.3% had post COVID-19 condition. These findings will help inform evidence-based preventive and therapeutic strategies for patients with hematologic malignancies and COVID-19 diagnosis.
Adenoid Cystic Carcinoma (AdCC): A Clinical Survey of a Large Patient Cohort
Authors: Zupancic Mark , Näsman Anders , Berglund Anders , Dalianis Tina , Friesland Signe
Published: February 2023

Adenoid cystic carcinoma (AdCC), a rare heterogenous disease, presents diagnostic, prognostic, and therapeutic challenges. To obtain more knowledge, we conducted a retrospective study on a cohort of 155 patients diagnosed in 2000–2022 with AdCC of the head and neck in Stockholm and investigated several clinical parameters in correlation to treatment and prognosis in the 142/155 patients treated with curative intent. The strongest favourable prognostic factors were early disease stage (stage I and II) as compared to late disease (stage III and IV) and major salivary gland subsite as compared to other subsites, with the best prognosis in the parotid gland, irrespective of the stage of the disease. Notably, in contrast to some studies, a significant correlation to survival was not found for perineural invasion or radical surgery. However, similar to others, we confirmed that other common prognostic factors, e.g., smoking, age, and gender, did not correlate to survival and should not be used for prognostication of AdCC of the head and neck. To conclude, in AdCC early disease stage, major salivary gland subsite and multimodal treatment were the strongest favourable prognostic factors, while this was not the case for age, gender and smoking nor perineural invasion and radical surgery.
Inter- and Intra-Observer Agreement of PD-L1 SP142 Scoring in Breast Carcinoma—A Large Multi-Institutional International Study
Authors: Zaakouk Mohamed , Van Bockstal Mieke , Galant Christine , Callagy Grace , Provenzano Elena , Hunt Roger , D’Arrigo Corrado , Badr Nahla M. , O’Sullivan Brendan , Starczynski Jane , Tanchel Bruce , Mir Yasmeen , Lewis Paul , Shaaban Abeer M.
Published: February 2023

The assessment of PD-L1 expression in TNBC is a prerequisite for selecting patients for immunotherapy. The accurate assessment of PD-L1 is pivotal, but the data suggest poor reproducibility. A total of 100 core biopsies were stained using the VENTANA Roche SP142 assay, scanned and scored by 12 pathologists. Absolute agreement, consensus scoring, Cohen’s Kappa and intraclass correlation coefficient (ICC) were assessed. A second scoring round after a washout period to assess intra-observer agreement was carried out. Absolute agreement occurred in 52% and 60% of cases in the first and second round, respectively. Overall agreement was substantial (Kappa 0.654–0.655) and higher for expert pathologists, particularly on scoring TNBC (6.00 vs. 0.568 in the second round). The intra-observer agreement was substantial to almost perfect (Kappa: 0.667–0.956), regardless of PD-L1 scoring experience. The expert scorers were more concordant in evaluating staining percentage compared with the non-experienced scorers (R2 = 0.920 vs. 0.890). Discordance predominantly occurred in low-expressing cases around the 1% value. Some technical reasons contributed to the discordance. The study shows reassuringly strong inter- and intra-observer concordance among pathologists in PD-L1 scoring. A proportion of low-expressors remain challenging to assess, and these would benefit from addressing the technical issues, testing a different sample and/or referring for expert opinions.
Unemployment Status Subsequent to Cancer Diagnosis and Therapies: A Systematic Review and Meta-Analysis
Authors: Chimienti Martina , Morlino Giustino , Ingravalle Fabio , Vinci Antonio , Colarusso Emilio , De Santo Carolina , Formosa Valeria , Gentile Lavinia , Lorusso Grazia , Mosconi Claudia , Scaramella Martina , Rosca Virginia , Veneziano Elena , Torino Francesco , Emberti Gialloreti Leonardo , Palombi Leonardo
Published: February 2023

The purpose of our study is to examine whether cancer and treatments are associated with job loss or changes in employment status. Eight prospective studies were included in the systematic review and meta-analysis, with a population aged 18–65 years, analyzing treatment regimen and psychophysical and social status in post-cancer follow-up of at least 2 years. In the meta-analysis, a comparison was made between recovered unemployed cases and cases from a standard reference population. Results are summarized graphically using a forest plot. We showed that cancer and subsequent treatment are risk factors for unemployment with an overall relative risk of 7.24 (lnRR: 1.98, 95% CI: 1.32–2.63) or for change in employment status. Individuals undergoing chemotherapy and/or radiation treatment and those with brain and colorectal cancers are more likely to develop disabilities that negatively affect the risk of unemployment. Finally, variables such as low level education, female sex, older age, and being overweight before starting therapy are associated with higher risk of unemployment. In the future, it will be necessary for people with cancer to have access to specific health, social welfare, and employment support programs. In addition, it is desirable that they become more involved in their choice of therapeutic treatment.
Melanoma Mortality Trends in 28 European Countries: A Retrospective Analysis for the Years 1960–2020
Authors: Koczkodaj Paweł , Sulkowska Urszula , Didkowska Joanna , Rutkowski Piotr , Mańczuk Marta
Published: February 2023

Background: In 2020, in 27 European Union (EU) Member States, melanoma accounted for 4% of all new cancer cases and 1.3% of all cancer deaths, making melanoma the fifth most common malignancy and placing it in the 15 most frequent causes of cancer deaths in the EU-27. The main aim of our study was to investigate melanoma mortality trends in 25 EU Member States and three non-EU countries (Norway, Russia, and Switzerland) in a broad time perspective (1960–2020) in a younger (45–74 years old) vs. older age group (75+). Methods: We identified melanoma deaths defined by ICD-10 codes C-43 for individuals aged 45–74 and 75+ years old between 1960–2020 in 25 EU Member States (excluding Iceland, Luxembourg, and Malta) and in 3 non-EU countries—Norway, Russia, and Switzerland. Age-standardized melanoma mortality rates (ASR) were computed using the direct age-standardization for Segi’s World Standard Population. To determine melanoma-mortality trends with 95% confidence intervals (CI), Joinpoint regression was applied. Our analysis used the Join-point Regression Program, version 4.3.1.0 (National Cancer Institute, Bethesda, MD, USA). Results: Regardless of the considered age groups, in all investigated countries, in general, melanoma standardized mortality rates were higher for men than women. Considering the age group 45–74, the highest number of countries was characterized by decreasing melanoma-mortality trends in both sexes—14 countries. Contrarily, the highest representation of countries in the age group 75+ was connected with increasing melanoma-mortality trends in both sexes—26 countries. Moreover, considering the older age group—75+—there was no country with a decreasing melanoma mortality in both sexes. Conclusions: Investigated melanoma-mortality trends vary in individual countries and age groups; however, a highly concerning phenomenon—increasing melanoma-mortality rates in both sexes—was observed in 7 countries for the younger age group and in as many as 26 countries for the older age group. There is a need for coordinated public-health actions to address this issue.
Cancer Survival and Travel Time to Nearest Reference Care Center for 10 Cancer Sites: An Analysis of 21 French Cancer Registries
Authors: Gardy Joséphine , Wilson Sarah , Guizard Anne-Valérie , Bouvier Véronique , Tron Laure , Launay Ludivine , Alves Arnaud ,   on behalf of the Francim Group, Launoy Guy , Molinié Florence , Bryère Joséphine , Dejardin Olivier
Published: February 2023

Background: The impact of several non-clinical factors on cancer survival is poorly understood. The aim of this study was to investigate the influence of travel time to the nearest referral center on survival of patients with cancer. Patients and methods: The study used data from the French Network of Cancer Registries that combines all the French population-based cancer registries. For this study, we included the 10 most common solid invasive cancer sites in France between 1 January 2013 and 31 December 2015, representing 160,634 cases. Net survival was measured and estimated using flexible parametric survival models. Flexible excess mortality modelling was performed to investigate the association between travel time to the nearest referral center and patient survival. To allow the most flexible effects, restricted cubic splines were used to investigate the influence of travel times to the nearest cancer center on excess hazard ratio. Results: Among the 1-year and 5-year net survival results, lower survival was observed for patients residing farthest from the referral center for half of the included cancer types. The remoteness gap in survival was estimated to be up to 10% at 5 years for skin melanoma in men and 7% for lung cancer in women. The pattern of the effect of travel time was highly different according to tumor type, being either linear, reverse U-shape, non-significant, or better for more remote patients. For some sites restricted cubic splines of the effect of travel time on excess mortality were observed with a higher excess risk ratio as travel time increased. Conclusions: For numerous cancer sites, our results reveal geographical inequalities, with remote patients experiencing a worse prognosis, aside from the notable exception of prostate cancer. Future studies should evaluate the remoteness gap in more detail with more explanatory factors.
B Cells in Breast Cancer Pathology
Authors: Li Mengyuan , Quintana Angela , Alberts Elena , Hung Miu Shing , Boulat Victoire , Ripoll Mercè Martí , Grigoriadis Anita
Published: February 2023

B cells have recently become a focus in breast cancer pathology due to their influence on tumour regression, prognosis, and response to treatment, besides their contribution to antigen presentation, immunoglobulin production, and regulation of adaptive responses. As our understanding of diverse B cell subsets in eliciting both pro- and anti-inflammatory responses in breast cancer patients increases, it has become pertinent to address the molecular and clinical relevance of these immune cell populations within the tumour microenvironment (TME). At the primary tumour site, B cells are either found spatially dispersed or aggregated in so-called tertiary lymphoid structures (TLS). In axillary lymph nodes (LNs), B cell populations, amongst a plethora of activities, undergo germinal centre reactions to ensure humoral immunity. With the recent approval for the addition of immunotherapeutic drugs as a treatment option in the early and metastatic settings for triple-negative breast cancer (TNBC) patients, B cell populations or TLS may resemble valuable biomarkers for immunotherapy responses in certain breast cancer subgroups. New technologies such as spatially defined sequencing techniques, multiplex imaging, and digital technologies have further deciphered the diversity of B cells and the morphological structures in which they appear in the tumour and LNs. Thus, in this review, we comprehensively summarise the current knowledge of B cells in breast cancer. In addition, we provide a user-friendly single-cell RNA-sequencing platform, called “B singLe cEll rna-Seq browSer” (BLESS) platform, with a focus on the B cells in breast cancer patients to interrogate the latest publicly available single-cell RNA-sequencing data collected from diverse breast cancer studies. Finally, we explore their clinical relevance as biomarkers or molecular targets for future interventions.
The Role of the A-Site Cation on the Bifunctional Electrocatalytic Activities of Ln0.5Sr0.5CoO3-δ (Ln = La, Pr and Sm) for Rechargeable Zinc–Air Batteries
Authors: Li Pengzhang , Huang Qing , Yang Wei , Tian Chuanjin , Liu Yumin , Zhao Wenyan , Lu Xiaojie , Cao Zhenbao , Wang Changan , Xie Zhipeng
Published: February 2023

Developing efficient bifunctional electrocatalysts for both the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER) is crucial for the large-scale application of rechargeable zinc–air batteries. Perovskite oxides are attractive candidates as bifunctional electrocatalysts. Herein, Ln0.5Sr0.5CoO3-δ (Ln = La, Pr and Sm) was prepared by the sol-gel method and evaluated as bifunctional electrocatalysts for both ORR and OER. Compare with La0.5Sr0.5CoO3-δ (LSC) and Sm0.5Sr0.5CoO3-δ (SSC), Pr0.5Sr0.5CoO3-δ (PSC) demonstrated the enhanced catalytic activity towards ORR with the limiting current density of 4.19 mA cm−2 at 0.40 V vs. RHE and OER with the potential of 1.75 V vs. RHE at 10 mA cm−2 as well as the Tafel slope of 105 mV dec−1. The higher Co3+/Co2+ ratio in PSC played an essential part in boosting the bifunctional electrocatalytic activities for ORR and OER. For demonstration, rechargeable zinc–air batteries with PSC as the air electrode displayed the maximum power density of 72 mW cm−2, the low charge-discharge voltage gap (1.01 V) at 10 mA cm−2 over 80 cycles and outstanding cycling stability. This work highlights the importance of A-site cations of the perovskite oxide as a valid strategy to improve ORR and OER activities.
Influence of the Valence of Iron on the NO Reduction by CO over Cu-Fe-Mordenite
Authors: Kotolevich Yulia , Zepeda-Partida Trino , Yocupicio-Gaxiola Rosario , Antúnez-Garcia Joel , Pelaez Luis , Avalos-Borja Miguel , Vázquez-Salas Pedro Jovanni , Fuentes-Moyado Sergio , Petranovskii Vitalii
Published: February 2023

A comprehensive study of the catalytic properties of the copper-iron binary system supported on mordenite, depending on the iron valence—CuFe2MOR and CuFe3MOR—was carried out, and redox ability has been considered as a decisive factor in determining catalytic efficiency. Acidity was studied by TPD-NH3, DRIFT-OH, and DRT methods. The total acidity of both samples was high. The Brönsted acidity is similar for both bimetallic samples and is explained by the acidity of zeolite; Lewis acidity varies greatly and depends on the exchange cations. A screening DRIFT study of CO and NO has shown redox capacity and demonstrated a potential for using these materials as catalysts for ambient protection. CuFe2MOR demonstrated stable Cu and Fe species, while CuFe3MOR showed redox dynamic species. As expected, CuFe3MOR displayed higher catalytic performance in NO reduction via CO oxidation, because of the easily reduced intermediate NO-complex adsorbed on the metallic Cu and Fe sites, which were observed through in situ DRIFT study.
Catalysts Based on Ni(Mg)Al-Layered Hydroxides Prepared by Mechanical Activation for Furfural Hydrogenation
Authors: Stepanova Liudmila N. , Kobzar Elena O. , Trenikhin Mikhail V. , Leont’eva Natalia N. , Serkova Aleksandra N. , Salanov Aleksei N. , Lavrenov Aleksandr V.
Published: February 2023

Ni(Mg)Al-layered hydroxides with molar ratios of (Ni + Mg)/Al = 2, 3, 4 and Ni/(Ni + Mg) = 0.1, 0.3, 0.5, 0.7 were synthesized by mechanochemical activation. It has been proven that the phase composition of the samples was presented by a single hydrotalcite phase up to Ni/(Ni + Mg) = 0.5. For the first time, catalysts based on Ni(Mg)Al-layered hydroxides prepared by a mechanochemical route have been studied in the reaction of furfural hydrogenation. The correlation between furfural conversion, the selectivity of the products, and the composition of the catalysts was established. The effect of phase composition, surface morphology, and microstructure on the activity of the catalysts was shown by XRD, SEM, and TEM. It was found that catalysts with Ni/(Ni + Mg) = 0.5 have the highest furfural conversion. Herewith, the product selectivity can be regulated by the (Ni + Mg)/Al ratio.
Notch Signaling Pathway in Tooth Shape Variations throughout Evolution
Authors: Mitsiadis Thimios A. , Pagella Pierfrancesco , Gomes Rodrigues Helder , Tsouknidas Alexander , Ramenzoni Liza L. , Radtke Freddy , Mehl Albert , Viriot Laurent
Published: February 2023

Evolutionary changes in vertebrates are linked to genetic alterations that often affect tooth crown shape, which is a criterion of speciation events. The Notch pathway is highly conserved between species and controls morphogenetic processes in most developing organs, including teeth. Epithelial loss of the Notch-ligand Jagged1 in developing mouse molars affects the location, size and interconnections of their cusps that lead to minor tooth crown shape modifications convergent to those observed along Muridae evolution. RNA sequencing analysis revealed that these alterations are due to the modulation of more than 2000 genes and that Notch signaling is a hub for significant morphogenetic networks, such as Wnts and Fibroblast Growth Factors. The modeling of these tooth crown changes in mutant mice, via a three-dimensional metamorphosis approach, allowed prediction of how Jagged1-associated mutations in humans could affect the morphology of their teeth. These results shed new light on Notch/Jagged1-mediated signaling as one of the crucial components for dental variations in evolution.
Application of Digital Holographic Microscopy to Analyze Changes in T-Cell Morphology in Response to Bacterial Challenge
Authors: vom Werth Kari Lavinia , Kemper Björn , Kampmeier Stefanie , Mellmann Alexander
Published: February 2023

Quantitative phase imaging (QPI) is a non-invasive, label-free technique used to detect aberrant cell morphologies caused by disease, thus providing a useful diagnostic approach. Here, we evaluated the potential of QPI to differentiate specific morphological changes in human primary T-cells exposed to various bacterial species and strains. Cells were challenged with sterile bacterial determinants, i.e., membrane vesicles or culture supernatants, derived from different Gram-positive and Gram-negative bacteria. Timelapse QPI by digital holographic microscopy (DHM) was applied to capture changes in T-cell morphology over time. After numerical reconstruction and image segmentation, we calculated single cell area, circularity and mean phase contrast. Upon bacterial challenge, T-cells underwent rapid morphological changes such as cell shrinkage, alterations of mean phase contrast and loss of cell integrity. Time course and intensity of this response varied between both different species and strains. The strongest effect was observed for treatment with S. aureus-derived culture supernatants that led to complete lysis of the cells. Furthermore, cell shrinkage and loss of circular shape was stronger in Gram-negative than in Gram-positive bacteria. Additionally, T-cell response to bacterial virulence factors was concentration-dependent, as decreases in cellular area and circularity were enhanced with increasing concentrations of bacterial determinants. Our findings clearly indicate that T-cell response to bacterial stress depends on the causative pathogen, and specific morphological alterations can be detected using DHM.
The Neuroprotective Activities of the Novel Multi-Target Iron-Chelators in Models of Alzheimer’s Disease, Amyotrophic Lateral Sclerosis and Aging
Authors: Kupershmidt Lana , Youdim Moussa B. H.
Published: February 2023

The concept of chelation therapy as a valuable therapeutic approach in neurological disorders led us to develop multi-target, non-toxic, lipophilic, brain-permeable compounds with iron chelation and anti-apoptotic properties for neurodegenerative diseases, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), age-related dementia and amyotrophic lateral sclerosis (ALS). Herein, we reviewed our two most effective such compounds, M30 and HLA20, based on a multimodal drug design paradigm. The compounds have been tested for their mechanisms of action using animal and cellular models such as APP/PS1 AD transgenic (Tg) mice, G93A-SOD1 mutant ALS Tg mice, C57BL/6 mice, Neuroblastoma × Spinal Cord-34 (NSC-34) hybrid cells, a battery of behavior tests, and various immunohistochemical and biochemical techniques. These novel iron chelators exhibit neuroprotective activities by attenuating relevant neurodegenerative pathology, promoting positive behavior changes, and up-regulating neuroprotective signaling pathways. Taken together, these results suggest that our multifunctional iron-chelating compounds can upregulate several neuroprotective-adaptive mechanisms and pro-survival signaling pathways in the brain and might function as ideal drugs for neurodegenerative disorders, such as PD, AD, ALS, and aging-related cognitive decline, in which oxidative stress and iron-mediated toxicity and dysregulation of iron homeostasis have been implicated.
Repercussions of COVID-19 Lockdown on Implementation of Children’s Rights to Education
Authors: Rahman Nurul Hidayat Ab , Mohd Zahir Mohd Zamre , Althabhawi Nabeel Mahdi
Published: February 2023

Lockdowns were among the control measures taken by many countries to hinder the virus from rapidly spreading. Public places had to be closed, including schools, as children are among the vulnerable groups that must always be protected. The primary purpose of this article is to explain children’s rights to education based on the Convention on the Rights of the Child (CRC) and the Sustainable Development Goals 2030 (SDG 2030). This article further investigates the consequences of COVID-19 lockdowns for ensuring that privilege for children. The article applies a qualitative method and observed that the lockdown strategy created challenges for all children with respect to receiving education, as the traditional learning pedagogy involving face-to-face meetings forcibly replaced by online learning. The principle of the best interest of the child is a primary consideration. In conclusion, governments must be responsible for providing all necessities to support education for all children, which is essential for human development.