bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel Erlotinib–Chalcone Hybrids Diminish Resistance in Head and Neck Cancer by Inducing Multiple Cell Death Mechanisms
Authors: Murányi József , Duró Cintia , Gurbi Bianka , Móra István , Varga Attila , Németh Krisztina , Simon József , Csala Miklós , Csámpai Antal
Published: February 2023

In a search for novel therapeutic options for head and neck squamous cell carcinomas (HNSCCs) generally treated with limited therapeutic success, we synthesized a series of novel erlotinib–chalcone molecular hybrids with 1,2,3-triazole and alkyne linkers and evaluated them for their anticancer activity on Fadu, Detroit 562 and SCC-25 HNSCC cell lines. Time- and dose-dependent cell viability measurements disclosed a significantly increased efficiency of the hybrids compared to the 1:1 combination of erlotinib and a reference chalcone. The clonogenic assay demonstrated that hybrids eradicate HNSCC cells in low micromolar concentrations. Experiments focusing on potential molecular targets indicate that the hybrids trigger the anticancer effect by a complementary mechanism of action that is independent of the canonical targets of their molecular fragments. Confocal microscopic imaging and real-time apoptosis/necrosis detection assay pointed to slightly different cell death mechanisms induced by the most prominent triazole- and alkyne-tethered hybrids (6a and 13, respectively). While 6a featured the lowest IC50 values on each of the three HNSCC cell lines, in Detroit 562 cells, this hybrid induced necrosis more markedly compared to 13. The therapeutic potential indicated by the observed anticancer efficacy of our selected hybrid molecules validates the concept of development and justifies further investigation to reveal the underlying mechanism of action.
Induced Pluripotent Stem Cell-Derived Organoids: Their Implication in COVID-19 Modeling
Authors: Csöbönyeiová Mária , Klein Martin , Kuniaková Marcela , Varga Ivan , Danišovič Ľuboš
Published: February 2023

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a significant global health issue. This novel virus’s high morbidity and mortality rates have prompted the scientific community to quickly find the best COVID-19 model to investigate all pathological processes underlining its activity and, more importantly, search for optimal drug therapy with minimal toxicity risk. The gold standard in disease modeling involves animal and monolayer culture models; however, these models do not fully reflect the response to human tissues affected by the virus. However, more physiological 3D in vitro culture models, such as spheroids and organoids derived from induced pluripotent stem cells (iPSCs), could serve as promising alternatives. Different iPSC-derived organoids, such as lung, cardiac, brain, intestinal, kidney, liver, nasal, retinal, skin, and pancreatic organoids, have already shown immense potential in COVID-19 modeling. In the present comprehensive review article, we summarize the current knowledge on COVID-19 modeling and drug screening using selected iPSC-derived 3D culture models, including lung, brain, intestinal, cardiac, blood vessels, liver, kidney, and inner ear organoids. Undoubtedly, according to reviewed studies, organoids are the state-of-the-art approach to COVID-19 modeling.
Peripheral Beta-2 Adrenergic Receptors Mediate the Sympathetic Efferent Activation from Central Nervous System to Splenocytes in a Mouse Model of Fibromyalgia
Authors: Yamashita Shiori , Dozono Naoki , Tobori Shota , Nagayasu Kazuki , Kaneko Shuji , Shirakawa Hisashi , Ueda Hiroshi
Published: February 2023

Abnormalities in the peripheral immune system are involved in the pathophysiology of fibromyalgia, although their contribution to the painful symptoms remains unknown. Our previous study reported the ability of splenocytes to develop pain-like behavior and an association between the central nervous system (CNS) and splenocytes. Since the spleen is directly innervated by sympathetic nerves, this study aimed to examine whether adrenergic receptors are necessary for pain development or maintenance using an acid saline-induced generalized pain (AcGP) model (an experimental model of fibromyalgia) and whether the activation of these receptors is also essential for pain reproduction by the adoptive transfer of AcGP splenocytes. The administration of selective β2-blockers, including one with only peripheral action, prevented the development but did not reverse the maintenance of pain-like behavior in acid saline-treated C57BL/6J mice. Neither a selective α1-blocker nor an anticholinergic drug affects the development of pain-like behavior. Furthermore, β2-blockade in donor AcGP mice eliminated pain reproduction in recipient mice injected with AcGP splenocytes. These results suggest that peripheral β2-adrenergic receptors play an important role in the efferent pathway from the CNS to splenocytes in pain development.
The Multifaceted Role and Regulation of Nlrp3 Inflammasome in Colitis-Associated Colo-Rectal Cancer: A Systematic Review
Authors: Zaharie Roxana , Valean Dan , Popa Calin , Fetti Alin , Zdrehus Claudiu , Puia Aida , Usatiuc Lia , Schlanger Diana , Zaharie Florin
Published: February 2023

Colitis-associated colo-rectal cancer remains the leading cause of mortality in inflammatory bowel diseases, with inflammation remaining one of the bridging points between the two pathologies. The NLRP3 inflammasome complex plays an important role in innate immunity; however, its misregulation can be responsible for the apparition of various pathologies such as ulcerative colitis. Our review focuses on the potential pathways of upregulation or downregulation of the NLRP3 complex, in addition to evaluating its role in the current clinical setting. Eighteen studies highlighted the potential pathways of NLRP3 complex regulation as well as its role in the metastatic process in colo-rectal cancer, with promising results. Further research is, however, needed in order to validate the results in a clinical setting.
Can Macrolophus pygmaeus (Hemiptera: Miridae) Mitigate the Damage Caused to Plants by Bemisia tabaci (Hemiptera: Aleyrodidae)?
Authors: Farina Alessia , Massimino Cocuzza Giuseppe Eros , Suma Pompeo , Rapisarda Carmelo
Published: February 2023

Nowadays, in protected vegetable crops, pest management based mainly on biological control represents the most sustainable alternative to pesticide use. The cotton whitefly, Bemisia tabaci, is one of the key pests that negatively impact the yield and quality of such crops in many agricultural systems. The predatory bug Macrolophus pygmaeus is one of the main natural enemies of the whitefly and is widely used for its control. However, the mirid can sometimes behave as a pest itself, causing damage to crops. In this study, we investigated the impact of M. pygmaeus as a plant feeder, by analyzing the combined impact of the whitefly pest and the predator bug on the morphology and physiology of potted eggplants under laboratory conditions. Our results showed no statistical differences between the heights of plants infested by the whitefly or by both insects compared with noninfested control plants. However, indirect chlorophyll content, photosynthetic performance, leaf area, and shoot dry weight were all greatly reduced in plants infested only by B. tabaci, compared with those infested by both pest and predator or with noninfested control plants. Contrarily, root area and dry weight values were more reduced in plants exposed to both of the insect species, compared with those infested only by the whitefly or compared with noninfested control plants, where the latter showed the highest values. These results show how the predator can significantly reduce the negative effects of B. tabaci infestation, limiting the damage it causes to host plants, though the effect of the mirid bug on the underground parts of the eggplant remains unclear. This information might be useful for a better understanding of the role that M. pygmaeus plays in plant growth, as well as for the development of management strategies to successfully control infestations by B. tabaci in cropping environments.
Artificial Intelligence in Hypertension Management: An Ace up Your Sleeve
Authors: Visco Valeria , Izzo Carmine , Mancusi Costantino , Rispoli Antonella , Tedeschi Michele , Virtuoso Nicola , Giano Angelo , Gioia Renato , Melfi Americo , Serio Bianca , Rusciano Maria Rosaria , Di Pietro Paola , Bramanti Alessia , Galasso Gennaro , D’Angelo Gianni , Carrizzo Albino , Vecchione Carmine , Ciccarelli Michele
Published: February 2023

Arterial hypertension (AH) is a progressive issue that grows in importance with the increased average age of the world population. The potential role of artificial intelligence (AI) in its prevention and treatment is firmly recognized. Indeed, AI application allows personalized medicine and tailored treatment for each patient. Specifically, this article reviews the benefits of AI in AH management, pointing out diagnostic and therapeutic improvements without ignoring the limitations of this innovative scientific approach. Consequently, we conducted a detailed search on AI applications in AH: the articles (quantitative and qualitative) reviewed in this paper were obtained by searching journal databases such as PubMed and subject-specific professional websites, including Google Scholar. The search terms included artificial intelligence, artificial neural network, deep learning, machine learning, big data, arterial hypertension, blood pressure, blood pressure measurement, cardiovascular disease, and personalized medicine. Specifically, AI-based systems could help continuously monitor BP using wearable technologies; in particular, BP can be estimated from a photoplethysmograph (PPG) signal obtained from a smartphone or a smartwatch using DL. Furthermore, thanks to ML algorithms, it is possible to identify new hypertension genes for the early diagnosis of AH and the prevention of complications. Moreover, integrating AI with omics-based technologies will lead to the definition of the trajectory of the hypertensive patient and the use of the most appropriate drug. However, AI is not free from technical issues and biases, such as over/underfitting, the “black-box” nature of many ML algorithms, and patient data privacy. In conclusion, AI-based systems will change clinical practice for AH by identifying patient trajectories for new, personalized care plans and predicting patients’ risks and necessary therapy adjustments due to changes in disease progression and/or therapy response.
Recurrent Abortion and the Involvement of Killer-Cell Immunoglobulin-like Receptor (KIR) Genes, Activated T Cells, NK Abnormalities, and Cytokine Profiles
Authors: Andreescu Mihaela , Frîncu Francesca , Plotogea Mihaela , Mehedințu Claudia
Published: February 2023

Immune tolerance at the feto-maternal interface is crucial for the growth of the semi-allograft fetus in the womb. The outcome of pregnancy is dependent on a fine balance between various immunological forces. For a long time, the potential role of the immune system in pregnancy disorders has remained enigmatic. Current evidence has revealed that natural killer (NK) cells are the predominant immune cell population in the uterine decidua. NK cells cooperate with T-cells to provide an optimal microenvironment for the growth of the developing fetus by producing cytokines, chemokines, and angiogenic factors. These factors support trophoblast migration and angiogenesis which regulates the process of placentation. NK cells differentiate between “self” and “non-self” through their surface receptors known as killer-cell immunoglobulin-like receptors (KIRs). They induce immune tolerance through communication via their KIR and fetal human leucocyte antigens (HLA). KIRs are surface receptors of NKs that comprise both activating and inhibiting receptors. Due to the wide diversity manifested by its genes, the KIR repertoire is different in each individual. Significant evidence has implicated KIRs in recurrent spontaneous abortion (RSA); however, maternal KIR gene diversity in RSA is still unclear. Research has shown that immunological aberrancies including activating KIRs, NK abnormalities, and T cell downregulation are risk factors for RSA. In this review, we discuss relevant data from experimental studies on NK cell abnormalities, KIR, and T-cells in the incidence of recurrent spontaneous abortion.
Predictive Factors and Clinical Impacts of Delayed Isolation of Tuberculosis during Hospital Admission
Authors: Lee Inhan , Kang Soyoung , Chin Bumsik , Joh Joon-Sung , Jeong Ina , Kim Junghyun , Kim Joohae , Lee Ji Yeon
Published: February 2023

Delayed isolation of tuberculosis (TB) can cause unexpected exposure of healthcare workers (HCWs). This study identified the predictive factors and clinical impact of delayed isolation. We retrospectively reviewed the electronic medical records of index patients and HCWs who underwent contact investigation after TB exposure during hospitalization at the National Medical Center, between January 2018 and July 2021. Among the 25 index patients, 23 (92.0%) were diagnosed with TB based on the molecular assay, and 18 (72.0%) had a negative acid-fast bacilli smear. Sixteen (64.0%) patients were hospitalized via the emergency room, and 18 (72.0%) were admitted to a non-pulmonology/infectious disease department. According to the patterns of delayed isolation, patients were classified into five categories. Among 157 close-contact events in 125 HCWs, 75 (47.8%) occurred in Category A. Twenty-five (20%) HCWs had multiple TB exposures (n = 57 events), of whom 37 (64.9%) belonged to Category A (missed during emergency situations). After contact tracing, latent TB infection was diagnosed in one (1.2%) HCW in Category A, who was exposed during intubation. Delayed isolation and TB exposure mostly occurred during pre-admission in emergency situations. Effective TB screening and infection control are necessary to protect HCWs, especially those who routinely contact new patients in high-risk departments.
Evaluation of the First-Year Data from an HPV Vaccination Van Program in South Carolina, U.S.
Authors: Ford Marvella , Cartmell Kathleen , Malek Angela , Le Phuong , Keeve Chloe , Sanders I’Ayana , Ross Jerlinda , Slan Melanie , McLauren Joan , Platt Mina , Gomez Ellen , Zserai Jessica , Poore Beth , Cody Christina , Ladd Victoria , Beattie Mary , Sudduth J. , Kreps Kapri , Roberts James
Published: February 2023

Human papillomavirus (HPV) infections are linked to at least six different types of cancer. The Medical University of South Carolina (MUSC) Hollings Cancer Center (HCC) and Department of Pediatrics leaders identified suboptimal rates of HPV vaccinations in rural and medically underserved communities in South Carolina (SC). To address this major public health problem in SC, they received funding from the HealthyMe/HealthySC (HMHSC) program and HCC to create a statewide community engagement-focused HPV Vaccination Van Program in October 2021. The Program provides HPV vaccinations and other childhood immunizations in school districts and HMHSC health clinics throughout SC, focusing on children aged 9–18 who are eligible for the U.S. Centers for Disease Control and Prevention’s Vaccines for Children Program. As of 14 December 2022, the Program administered vaccinations in 16 counties of SC to 552 participants, 243 of whom received HPV vaccinations and were predominantly female (57.2%), aged 4–18 (95.9%), and self-identified as White (44.0%), Black (33.2%), or Hispanic/Latino (15.1%). Most had Medicaid (53.1%)/no insurance coverage (25.1%). The Program is expected to expand as the Program’s relationship with SC’s school districts grows. The Program provides a model for delivering mobile HPV vaccinations to rural children, thus reducing their cancer risk.
Gender Differences, Motor Skills and Physical Fitness Heterogeneity in Adults with Down’s Syndrome
Authors: Covain Sandro , Baillieul Sébastien , Nguyen Thai Duy , Guinot Michel , Doutreleau Stéphane , Bricout Véronique-Aurélie
Published: February 2023

Background—Adults with Down’s syndrome (DS) present lower physical fitness associated with heightened sedentary behaviors and motor skills impairments. Their etiologies and determinants seem to be heterogeneous. This study aims to evaluate physical fitness in adults with DS and to identify specific physical fitness profiles depending on gender and physical activity levels. Methods—Forty adults with DS (16 women, 24 men, 29.7 ± 7.5 years) performed six tests from the EUROFIT Battery and Motor Assessment Battery for Children (MAB-C). Their maximal aerobic capacity was assessed using an incremental treadmill test to assess (VO2peak). Ecological, physical activity, and sedentary levels were evaluated subjectively (Global Physical Activity Questionnaire) and objectively using an Actigraph GT9X® accelerometer over a seven-day period. Results—VO2peak and isometric strength were significantly lower for women (p < 0.01), whereas men had significantly lower flexibility than women (p < 0.05). Using a principal component analysis and an agglomerative hierarchical analysis, we identified three clusters. Cluster 1 (n = 14; 50% men; Body Mass index = 28.3 ± 4.3) was characterized by significantly poorer physical fitness variables (VO2peak (p < 0.01), strength (p < 0.01) and balance (p < 0.05)) compared to Clusters 2 and 3. Cluster 2 (n = 19; 58% men; Body Mass index = 22.9 ± 2.0) and Cluster 3 (n = 19; 58% men; BMI = 22.9 ± 1.9) were characterized by subjects with comparable physical fitness profiles, except for the balance capacities, which were significantly lower in Cluster 3 (p < 0.05). Conclusions—DS subjects exhibited high heterogeneity in terms of physical fitness, PA, and sedentary levels, with a significant gender effect. The present findings are important to identify subjects at higher risk of sedentary behaviors and impaired motor capacities to develop personalized PA programs.
Blood Count-Derived Inflammatory Markers and Acute Complications of Ischemic Heart Disease in Elderly Women
Authors: Dziedzic Ewelina A. , Gąsior Jakub S. , Tuzimek Agnieszka , Kochman Wacław
Published: February 2023

Coronary artery disease (CAD) in women occurs later than in men. Underlying atherosclerosis, a chronic process of lipoprotein deposition in arterial walls with a prominent inflammatory component, is influenced by several risk factors. In women, commonly used inflammatory markers are generally found to be related to the occurrence of acute coronary syndrome (ACS), as well as the development of other diseases that influence CAD. New inflammatory markers derived from total blood count—systemic inflammatory response index (SII), systemic inflammatory reaction index (SIRI), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR), and neutrophil-lymphocyte ratio (NLR)—were analyzed in the group of 244 elderly, postmenopausal women with the diagnosis of ACS or stable CAD. SII, SIRI, MLR, and NLR were significantly higher in women with ACS compared to those with stable CAD (p < 0.05 for all)—the highest values were observed in women with NSTEMI. MLR from new inflammatory markers, HDL, and history of MI turned out to be significant factors associated with ACS. These results suggest that MLR as representative of blood count-derived inflammatory markers may be considered as additional CVD risk factors in women with suspected ACS.
Alteration of the Functional Connectivity of the Cortical Areas Characterized by the Presence of Von Economo Neurons in Schizophrenia, a Pilot Study
Authors: Brasso Claudio , Stanziano Mario , Bosco Francesca Marina , Morese Rosalba , Valentini Maria Consuelo , Vercelli Alessandro , Rocca Paola
Published: February 2023

Von Economo neurons (VENs) are rod, stick, or corkscrew cells mostly located in layer V of the frontoinsular and anterior cingulate cortices. VENs are projection neurons related to human-like social cognitive abilities. Post-mortem histological studies found VEN alterations in several neuropsychiatric disorders, including schizophrenia (SZ). This pilot study aimed to evaluate the role of VEN-containing areas in shaping patterns of resting-state brain activation in patients with SZ (n = 20) compared to healthy controls (HCs; n = 20). We performed a functional connectivity analysis seeded in the cortical areas with the highest density of VENs followed by fuzzy clustering. The alterations found in the SZ group were correlated with psychopathological, cognitive, and functioning variables. We found a frontotemporal network that was shared by four clusters overlapping with the salience, superior-frontal, orbitofrontal, and central executive networks. Differences between the HC and SZ groups emerged only in the salience network. The functional connectivity of the right anterior insula and ventral tegmental area within this network were negatively correlated with experiential negative symptoms and positively correlated with functioning. This study provides some evidence to show that in vivo, VEN-enriched cortical areas are associated with an altered resting-state brain activity in people with SZ.
Challenges in ARDS Definition, Management, and Identification of Effective Personalized Therapies
Authors: Battaglini Denise , Fazzini Brigitta , Silva Pedro Leme , Cruz Fernanda Ferreira , Ball Lorenzo , Robba Chiara , Rocco Patricia R. M. , Pelosi Paolo
Published: February 2023

Over the last decade, the management of acute respiratory distress syndrome (ARDS) has made considerable progress both regarding supportive and pharmacologic therapies. Lung protective mechanical ventilation is the cornerstone of ARDS management. Current recommendations on mechanical ventilation in ARDS include the use of low tidal volume (VT) 4–6 mL/kg of predicted body weight, plateau pressure (PPLAT) < 30 cmH2O, and driving pressure (∆P) < 14 cmH2O. Moreover, positive end-expiratory pressure should be individualized. Recently, variables such as mechanical power and transpulmonary pressure seem promising for limiting ventilator-induced lung injury and optimizing ventilator settings. Rescue therapies such as recruitment maneuvers, vasodilators, prone positioning, extracorporeal membrane oxygenation, and extracorporeal carbon dioxide removal have been considered for patients with severe ARDS. Regarding pharmacotherapies, despite more than 50 years of research, no effective treatment has yet been found. However, the identification of ARDS sub-phenotypes has revealed that some pharmacologic therapies that have failed to provide benefits when considering all patients with ARDS can show beneficial effects when these patients were stratified into specific sub-populations; for example, those with hyperinflammation/hypoinflammation. The aim of this narrative review is to provide an overview on current advances in the management of ARDS from mechanical ventilation to pharmacological treatments, including personalized therapy.
Percutaneous Coronary Intervention Is Not Superior to Optimal Medical Therapy in Chronic Coronary Syndrome: A Meta-Analysis
Authors: Bytyçi Ibadete , Morina Defrim , Bytyqi Sefer , Bajraktari Gani , Henein Michael Y.
Published: February 2023

(1) Background and Aim: Conflicting evidence exists regarding the benefits of percutaneous coronary intervention (PCI) on survival and symptomatic relief of patients with chronic coronary syndrome (CCS) compared with optimal medical therapy (OMT). This meta-analysis is to evaluate the short- and long-term clinical benefit of PCI over and above OMT in CCS. (2) Methods: Main endpoints were major adverse cardiac events (MACEs), all-cause mortality, cardiovascular (CV) mortality, myocardial infarction (MI), urgent revascularization, stroke hospitalization, and quality of life (QoL). Clinical endpoints at very short (≤3 months), short- (<12 months), and long-term (≥ 12 months) follow-up were evaluated. (3) Results: Fifteen RCTs with a total of 16,443 patients with CCS (PCI n = 8307 and OMT n = 8136) were included in the meta-analysis. At mean follow-up of 27.7 months, the PCI group had similar risk of MACE (18.2 vs. 19.2 %; p < 0.32), all-cause mortality (7.09 vs. 7.88%; p = 0.56), CV mortality (8.74 vs. 9.87%; p = 0.30), MI (7.69 vs. 8.29%; p = 0.32), revascularization (11.2 vs. 18.3%; p = 0.08), stroke (2.18 vs. 1.41%; p = 0.10), and hospitalization for anginal symptoms (13.5 vs. 13.9%; p = 0.69) compared with OMT. These results were similar at short- and long-term follow-up. At the very short-term follow-up, PCI patients had greater improvement in the QoL including physical limitation, angina frequency, stability, and treatment satisfaction (p < 0.05 for all) but such benefits disappeared at the long-term follow-up. (4) Conclusions: PCI treatment of CCS does not provide any long-term clinical benefit compared with OMT. These results should have significant clinical implications in optimizing patient’s selection for PCI treatment.
The PD-L1 Expression and Tumor-Infiltrating Immune Cells Predict an Unfavorable Prognosis in Pancreatic Ductal Adenocarcinoma and Adenosquamous Carcinoma
Authors: Zhang Zhiwei , Xiong Qunli , Xu Yongfeng , Cai Xuebin , Zhang Lisha , Zhu Qing
Published: February 2023

The tumor microenvironment (TME) plays a vital role in the development, progression, and metastasis of pancreatic cancer (PC). The composition of the TME and its potential prognostic value remains to be fully understood, especially in adenosquamous carcinoma of pancreas (ASCP) patients. Immunohistochemistry was used to explore the clinical significance of CD3, CD4, CD8, FoxP3, and PD-L1 expression within the TME and to identify correlations with the prognosis of PC in a series of 29 patients with ASCP and 54 patients with pancreatic ductal adenocarcinoma (PDAC). Data from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) were accessed to obtain the scRNA-seq data and transcriptome profiles. Seurat was used to process the scRNA-seq data, and CellChat was used to analyze cell–cell communication. CIBERSORT was used to approximate the constitution of tumor-infiltrating immune cell (TICs) profiles. Higher levels of PD-L1 were linked with a shorter overall survival in ASCP (p = 0.0007) and PDAC (p = 0.0594). A higher expression of CD3+ and CD8+ T-cell infiltration was significantly correlated with a better prognosis in PC. By influencing the composition of tumor-infiltrating immune cells (TICs), high levels of PD-L1 expression are linked with a shorter overall survival in ASCP and PDAC.
Hepatoid Adenocarcinoma of the Lung: A Review of the Most Updated Literature and a Presentation of Three Cases
Authors: Bonis Alessandro , Dell’Amore Andrea , Verzeletti Vincenzo , Melan Luca , Zambello Giovanni , Nardocci Chiara , Comacchio Giovanni Maria , Pezzuto Federica , Calabrese Fiorella , Rea Federico
Published: February 2023

In a Surgical Thoracic Center, two females and a man were unexpectedly diagnosed with hepatoid adenocarcinoma of the lung (HAL) in a single year. HAL is a rare lung cancer with pathological features of hepatocellular carcinoma with no evidence of liver tumor or other primitive sites of neoplasms. As of today, a comprehensive treatment is still not written. We reviewed the most updated literature on HAL, aiming to highlight the proposed treatments available, and comparing them in terms of survival. General hallmarks of HAL are confirmed: it typically affects middle-aged, heavy-smoker males with a median of 5 cm bulky right upper lobe mass. Overall survival remains poor (13 months), with a longer but non-significant survival in females. Treatments are still unsatisfactory today: surgery guarantees a small benefit compared to non-operated HALs, and only N0 patients demonstrated improved survival (p = 0.04) compared to N1, N2, and N3. Even though the histology is fearsome, these are probably the patients who will benefit from upfront surgery. Chemotherapy seemed to behave as surgery, and there is no statistical difference between chemotherapy only, surgery, or adjuvant treatments, even though adjuvant treatments tend to be more successful. New chemotherapies have been reported with notable results in recent years, such as Tyrosine Kinase Inhibitors and monoclonal antibodies. In this complicated picture, new cases are needed to further build shared evidence in terms of diagnosis, treatments, and survival opportunities.
Long-Term Outcomes of Tachycardia-Induced Cardiomyopathy Compared with Idiopathic Dilated Cardiomyopathy
Authors: Katz Moshe , Meitus Amit , Arad Michael , Aizer Anthony , Nof Eyal , Beinart Roy
Published: February 2023

Background: data on the natural course and prognosis of tachycardia-induced cardiomyopathy (TICMP) and comparison with idiopathic dilated cardiomyopathies (IDCM) are scarce. Objective: To compare the clinical presentation, comorbidities, and long-term outcomes of TICMP patients with IDCM patients. Methods: a retrospective cohort study of patients hospitalized with new-onset TICMP or IDCM. The primary endpoint was a composite of death, myocardial infarction, thromboembolic events, assist device, heart transplantation, and ventricular tachycardia or fibrillation (VT/VF). The secondary endpoint was recurrent hospitalization due to heart failure (HF) exacerbation. Results: the cohort was comprised of 64 TICMP and 66 IDCM patients. The primary composite endpoint and all-cause mortality were similar between the groups during a median follow-up of ~6 years (36% versus 29%, p = 0.33 and 22% versus 15%, p = 0.15, respectively). Survival analysis showed no significant difference between TICMP and IDCM groups for the composite endpoint (p = 0.75), all-cause mortality (p = 0.65), and hospitalizations due to heart failure exacerbation. Nonetheless, the incidence of recurrent hospitalization was significantly higher in TICMP patients (incidence rate ratio 1.59; p = 0.009). Conclusions: patients with TICMP have similar long-term outcomes as those with IDCM. However, it portends a higher rate of HF readmissions, mostly due to arrhythmia recurrences.
Gelatin Matrix as Functional Biomaterial for Immobilization of Nanoparticles of Metal-Containing Compounds
Authors: Mikhailov Oleg V.
Published: February 2023

The data concerning the synthesis and physicochemical characteristics of specific functional biomaterials—biopolymer-immobilized matrix systems based on gelatin as an array and chemical compounds, which include atoms of various metal elements—are systematized and discussed. The features of this biopolymer which determine the specific properties of the immobilized matrix systems formed by it and their reactivity, are noted. Data on gelatin-immobilized systems in which immobilized substances are elemental metals and coordination compounds formed as a result of redox processes, nucleophilic/electrophilic substitution reactions, and self-assembly (template synthesis), are presented. The possibilities of the practical use of metal-containing gelatin-immobilized systems are promising for the future; in particular, their potential in medicine and pharmacology as a vehicle for “targeted” drug delivery to various internal organs/tissues of the body, and, also, as potential biosensors is noted.
Permeability of Hydrate-Bearing Sediment Formed from CO2-N2 Mixture
Authors: Li Nan , Fan Ziyang , Ma Haoran , Jia Shuai , Kan Jingyu , Sun Changyu , Liu Shun
Published: February 2023

CO2-N2-mixture injection can be used for the exploitation and reformation of natural gas hydrate reservoirs. The permeability evolution of sediments in the presence of CO2-N2 hydrate is very important. In current permeability tests, hydrate-bearing sediment formed from CO2-N2 gas mixture is rarely involved. In this work, hydrate-bearing sediment was formed from CO2-N2 mixtures, and a constant flow method was employed to measure the permeability of the hydrate-bearing sediments. The effects of CO2 mole fraction and hydrate saturation on the permeability were investigated. The results show that gas composition is the key factor affecting hydrate formation. Hydrate saturation increases with increasing CO2 mole fraction in the gas mixture. The presence of hydrate formed from a CO2-N2 mixture leads to a sharp permeability reduction. The higher the fraction of CO2 in the injected gas mixture, the lower the sediment’s permeability. Our measured permeability data were also compared with and fitted to prediction models. The pore-filling model underestimates the permeability of hydrate-bearing sediments formed from a CO2-N2 gas mixture. The fitted hydrate saturation index in the Masuda model is 15.35, slightly higher than the general values, which means that the formed hydrates tend to occupy the pore center, and even block the pore throat.
Spermiotoxicity of Nano-TiO2 Compounds in the Sea Urchin Paracentrotus lividus (Lamarck, 1816): Considerations on Water Remediation
Authors: Ignoto Sara , Pecoraro Roberta , Scalisi Elena Maria , Contino Martina , Ferruggia Greta , Indelicato Stefania , Fiorenza Roberto , Balsamo Stefano Andrea , Impellizzeri Giuliana , Tiralongo Francesco , Salvaggio Antonio , Brundo Maria Violetta
Published: February 2023

Despite the great utility of nanoparticles (NPs) in water remediation, their effects on marine ecosystems are unknown and unpredictable. The toxicity of the most used nanoparticles, such as ZnO, Ag, and TiO2 on the purple sea urchin, Paracentrotus lividus (Lamarck, 1816), has been demonstrated by several authors. The aim of this study was to evaluate the effects of TiO2 sol-gel and TiO2-rGO nanocompounds on both vitality and motility of spermatozoa of P. lividus. The spermatozoa were exposed at different times (30 and 60 min) and concentrations (10, 20, 40 µg/mL) of both nano-TiO2 compounds. The results clearly showed a decrease in both vitality and motility of P. lividus spermatozoa exposed. In particular, vitality and motility were inversely related to both exposure time and concentration of TiO2 sol-gel and TiO2-rGO nanocompounds.
Dermatophytic Biofilms: Characteristics, Significance and Treatment Approaches
Authors: Markantonatou Anthi-Marina , Samaras Konstantinos , Vyzantiadis Timoleon-Achilleas
Published: February 2023

Microbes are found in the environment, possibly more often as biofilms than in planktonic forms. Biofilm formation has been described for several important fungal species. The presence of a dermatophytoma in a dermatophytic nail infection was the basis for the proposal that dermatophytes form biofilms as well. This could explain treatment failure and recurrent dermatophytic infections. Several investigators have performed in vitro and ex vivo experiments to study the formation of biofilms by dermatophytes and their properties. The nature of the biofilm structure itself contributes to fungal protection mechanisms against many harmful external agents, including antifungals. Thus, a different approach should be carried out regarding susceptibility testing and treatment. Concerning susceptibility testing, methods to evaluate either the inhibition of biofilm formation, or the ability to eradicate it, have been introduced. As for treatment, in addition to classical antifungal agents, some natural formulations, such as plant extracts or biosurfactants, and alternative approaches, such as photodynamic therapy, have been proposed. Studies that connect the results of the in vitro and ex vivo experimentation with clinical outcomes are required in order to verify the efficacy of these approaches in clinical practice.
Enhancement of Cell Adhesion by Anaplasma phagocytophilum Nucleolin-Interacting Protein AFAP
Authors: Tang Hongcheng , Zhang Daxiu , Jiang Fenfen , Yu Lifeng , Tang Hui , Zhu Jiafeng , Wu Shuyan , Niu Hua
Published: February 2023

Anaplasma phagocytophilum, the aetiologic agent of human granulocytic anaplasmosis (HGA), is an obligate intracellular Gram-negative bacterium. During infection, A. phagocytophilum enhances the adhesion of neutrophils to the infected endothelial cells. However, the bacterial factors contributing to this phenomenon remain unknown. In this study, we characterized a type IV secretion system substrate of A. phagocytophilum, AFAP (an actin filament-associated Anaplasma phagocytophilum protein) and found that it dynamically changed its pattern and subcellular location in cells and enhanced cell adhesion. Tandem affinity purification combined with mass spectrometry identified host nucleolin as an AFAP-interacting protein. Further study showed the disruption of nucleolin by RNA interference, and the treatment of a nucleolin-binding DNA aptamer AS1411 attenuated AFAP-mediated cell adhesion, indicating that AFAP enhanced cell adhesion in a nucleolin-dependent manner. The characterization of cell adhesion-enhancing AFAP and the identification of host nucleolin as its interaction partner may help understand the mechanism underlying A. phagocytophilum-promoting cell adhesion, facilitating the elucidation of HGA pathogenesis.
Risk Spillovers between Bitcoin and ASEAN+6 Stock Markets before and after COVID-19 Outbreak: A Comparative Analysis with Gold
Authors: Sinlapates Parichat , Sriwong Tanit , Chancharat Surachai
Published: February 2023

This paper applies the multivariate GARCH models to investigate the role of Bitcoin as a hedge and safe haven for ASEAN+6 stock markets compared to gold. We used daily data for the dates 2 January 2017–20 January 2023, covering the recent COVID-19 pandemic. The empirical findings provide compelling evidence of cross-market shock and volatility transmission between stock returns and Bitcoin returns in both directions. Therefore, the dynamics of Bitcoin returns significantly influence the volatility of stock returns, and the relationship also holds in reverse. All diagonal element estimations are statistically significant for both periods, as shown by the findings of the return and volatility spillovers between the returns of gold and the ASEAN+6 stock market. For most ASEAN+6 equity markets evaluated, Bitcoin and gold are not safe havens, and their inclusion increases the portfolio downside risk.
Agent-Based Modeling of Construction Firms’ Organizational Behavior in Public Tenders
Authors: Gladkikh Valeriya , Alekseev Aleksandr
Published: February 2023

A key problem of construction firms’ management and economy is organization of effective participation in public tenders. The direct executor, who determines the price of the contract, may be interested in obtaining as many contracts as possible. It means that his strategic behavior in tender may be to undervalue each individual offer. At the same time, such a strategy can be a source of risk of project loss because the actual costs may be lower than the price of the contract won. The management of the construction organization is not interested in this. On the other hand, overpricing strategy may lead to a reduction in the number of contracts won, which may not seem effective either for the head or for the executor of such an organization. The article discusses whether the profits of a construction firm can increase by using a more precise method of calculating the estimated cost. The second question is—which staff of a construction firm will benefit from using such methods? The aim of this work is to test these hypotheses with the instrumentality of agent-based modeling. Profit values of construction firms were obtained by the computer simulation of the construction firms’ strategic behavior in public tenders. Results of 1500 computer experiments are presented as a decision tree. It can be seen that when using a more precise method, construction firms win tenders almost two times less often. However, they incur losses many times less than with an inaccurate method. If a construction firm made a profit from the contracts won, the profit margin was almost always greater when using the more precise method. Moreover, the results of game-theoretic modeling are given. Values of the objective functions of the executor and head of the construction firm were obtained, taking into account the reward for contracts won and penalty for miscalculating the cost of work. It has been proved that using more precise methods for calculating the estimated cost is beneficial to both the head and the executor. It can be concluded that both hypotheses were confirmed and a precise method for calculating the cost increases the efficiency of a construction firm.
Implementation of Elliptic Curves in the Polynomial Blom Key Pre-Distribution Scheme for Wireless Sensor Networks and Distributed Ledger Technology
Authors: Antony Siti Noor Farwina Mohamad Anwar , Bahari Muhammad Fatihin Afiq
Published: February 2023

One of the challenges in securing wireless sensor networks (WSNs) is the key distribution; that is, a single shared key must first be known to a pair of communicating nodes before they can proceed with the secure encryption and decryption of the data. In 1984, Blom proposed a scheme called the symmetric key generation system as one method to solve this problem. Blom’s scheme has proven to be λ-secure, which means that a coalition of λ+1 nodes can break the scheme. In 2021, a novel and intriguing scheme based on Blom’s scheme was proposed. In this scheme, elliptic curves over a finite field are implemented in Blom’s scheme for the case when λ=1. However, the security of this scheme was not discussed. In this paper, we point out a mistake in the algorithm of this novel scheme and propose a way to fix it. The new fixed scheme is shown to be applicable for arbitrary λ. The security of the proposed scheme is also discussed. It is proven that the proposed scheme is also λ-secure with a certain condition. In addition, we also discuss the application of this proposed scheme in distributed ledger technology (DLT).
Regional Heterogeneity in China’s Rural Collectively Owned Commercialized Land Market: An Empirical Analysis from 2015–2020
Authors: Yang Shenjie , Wen Lanjiao
Published: February 2023

The ongoing collectively owned commercialized construction land market (CCCLM), established in China in 2015, calls for a deeper understanding of the market’s performance so as to promote integrated urban-rural development. This study provides an empirical analysis of the regional heterogeneity of CCCLM, based on 4595 collectively owned commercialized construction land (CCCL) transaction cases around the country from 2015 to 2020. The marketization degree measured with a weighted average approach indicates that the marketization level of CCCL is low, and typical pilots have a significant demonstration effect. The results show that pilot areas in the east have more active CCCL transactions, with higher quantities, areas, and transaction values of CCCL compared with central and western regions. However, most pilot areas use villagers’ self-governance organizations or mixed subjects as the implementation players, and trade CCCL by negotiation or listed conveyance. It turns out that the value of CCCL cannot be better realized in such a market environment because of its low degree of specialization and marketization. This study presents comprehensive empirical evidence for promoting the construction of the rural land market in China and in other transition economies worldwide.
Enzymatic Debridement of Deep Thermal Burns in the Russian Federation: First Experience
Authors: Alekseev Andrey A. , Malyutina Natalia B. , Bobrovnikov Alexander E. , Shoham Yaron
Published: February 2023

Since its approval in Europe a decade ago, NexoBrid® enzymatic debridement of deep thermal burns has been gaining acceptance as standard practice around the world. The purpose of this study is to report the first experience with NexoBrid® in the Russian Federation. During 2019–2020, we conducted a post-registration clinical study assessing the safety and treatment results of NexoBrid® enzymatic debridement. The study involved 15 adult patients suffering from deep thermal burns over an area ≤15% of their total body surface area. Patients were treated with NexoBrid® within 3 days of injury, followed by spontaneous or surgical wound closure. Complete eschar removal was achieved in twelve patients, 80% eschar removal in two patients, and 70% in one patient. Complete spontaneous epithelialization of wounds was achieved in 12 patients (80%) within 18 ± 1.9 days after the start of treatment. We did not witness pathological scarring during follow-up, and there were no significant safety issues throughout the study. Early use of NexoBrid® resulted in rapid, effective, and safe eschar removal with good results and sufficient preservation of viable dermis to allow for spontaneous healing in 80% of patients. These results demonstrate the ability to minimize surgical intervention and hopefully lead to better long-term scarring results.
Numerical Simulation of a New Designed Mechanical Seals with Spiral Groove Structures
Authors: He Tao , Zhang Qiangqiang , Yan Ying , Dong Jintong , Zhou Ping
Published: February 2023

The spiral groove seal has a strong hydrodynamic effect, but it has poor pollution resistance at the seal’s end and has unfavorable sealing stability. Circumferential waviness seals can use the fluid to clean the surface and have a strong ability to self-rush, protecting the main cover from contamination. This study presents a novel wave-tilt-dam seal design that integrates spiral groove structures to enhance the hydrodynamic performance of circumferential waviness seals. The objective of the research is to evaluate the mechanical effectiveness of this new design through simulation modeling, with a focus on the impact of structural parameters such as rotational speed and seal pressure on the hydrodynamic behavior under various operating conditions. The results of the study indicate that the new structure effectively improves the hydrodynamic performance of the liquid seal, resulting in a significant increase in film rigidity. Additionally, the study identifies optimal values for structural parameters under specific conditions. By addressing the limitations of traditional spiral groove seals and improving their hydrodynamic performance, this research contributes to the advancement of seal technology.
Investigation of the Optical Properties of Indium Tin Oxide Thin Films by Double Integration Sphere Combined with the Numerical IAD Method
Authors: Toral-Lopez Alejandro , Pérez María M. , Rodríguez-Águila Ana Belen , Cardona Juan C. , Ionescu Ana M. , Godoy Andres
Published: February 2023

Transparent conductive electrodes have become essential components of numerous optoelectronic devices. However, their optical properties are typically characterized by the direct transmittance achieved by making use of spectrophotometers, avoiding an in-depth knowledge of the processes involved in radiation attenuation. A different procedure based on the Double Integration Sphere combined with the numerical Inverse Adding-Doubling (IAD) method is employed in this work to provide a comprehensive description of the physical processes limiting the light transmittance in commercial indium tin oxide (ITO) deposited on flexible PET samples, highlighting the noticeable contribution of light scattering on the total extinction of radiation. Moreover, harnessing their flexibility, the samples were subjected to different mechanical stresses to assess their impact on the material’s optical and electrical properties.
Composite and Polymeric Materials for Dentistry: Enhancing Antimicrobial and Mechanical Properties
Authors: Chladek Grzegorz
Published: February 2023

Billions of people suffer from dental problems and that number is constantly increasing [...]