bluuebunny/crossref_metadata_2025 huggingface dataset:
A Single-Valued Neutrosophic Extension of the EDAS Method
Authors: Stanujkić Dragiša , Karabašević Darjan , Popović Gabrijela , Pamučar Dragan , Stević Željko , Zavadskas Edmundas Kazimieras , Smarandache Florentin
Published: September 2021

This manuscript aims to propose a new extension of the EDAS method, adapted for usage with single-valued neutrosophic numbers. By using single-valued neutrosophic numbers, the EDAS method can be more efficient for solving complex problems whose solution requires assessment and prediction, because truth- and falsity-membership functions can be used for expressing the level of satisfaction and dissatisfaction about an attitude. In addition, the indeterminacy-membership function can be used to point out the reliability of the information given with truth- and falsity-membership functions. Thus, the proposed extension of the EDAS method allows the use of a smaller number of complex evaluation criteria. The suitability and applicability of the proposed approach are presented through three illustrative examples.
Criteria for the Oscillation of Solutions to Linear Second-Order Delay Differential Equation with a Damping Term
Authors: Moaaz Osama , Elabbasy Elmetwally M. E. , Awrejcewicz Jan , Abdelnaser Aml
Published: September 2021

The aim of this work is to present new oscillation results for a class of second-order delay differential equations with damping term. The new criterion of oscillation depends on improving the asymptotic properties of the positive solutions of the studied equation by using an iterative technique. Our results extend some of the results recently published in the literature.
Molecular Characterization of Blastocystis from Animals and Their Caregivers at the Gdańsk Zoo (Poland) and the Assessment of Zoonotic Transmission
Authors: Rudzińska Monika , Kowalewska Beata , Waleron Małgorzata , Kalicki Mirosław , Sikorska Katarzyna , Szostakowska Beata
Published: September 2021

Blastocystis is a highly genetically diverse gut protist commonly found in humans and various animals. The role of animals in human infection is only partly understood. The aim of this study was to determine the host specificity and possibility of zoonotic transmission of this microorganism. Subtypes of Blastocystis isolated from 201 zoo animals and their 35 caregivers were identified by sequencing of the SSU rRNA gene. Blastocystis was found in 26.86% of animal and 17.14% of human samples. Both mammalian (ST1–ST3, ST5, ST8, ST10, ST13, ST14) and non-mammalian subtypes were detected. Of the subtypes found in non-human primates (ST1, ST2, ST3, and ST13), two subtypes (ST1 and ST3) were also detected in humans. The presence of identical ST1 sequences in three monkeys and their caregiver indicates the possibility of direct transmission of Blastocystis between these animals and humans. Detection of ST5 only in wild boars and peccaries, ST8 only in Marsupial, ST10 and ST14 only in Bovidae, and non-mammalian subtypes in reptiles suggests higher host specificity for these subtypes, and indicates that their transmission between animals and humans is unlikely. Additionally, this was probably the first time that ST5 was found in peccaries, ST2 in patas monkeys, and ST8 in red kangaroos.
Insight into the Lubrication and Adhesion Properties of Hyaluronan for Ocular Drug Delivery
Authors: Černohlávek Mikuláš , Brandejsová Martina , Štěpán Petr , Vagnerová Hana , Hermannová Martina , Kopecká Kateřina , Kulhánek Jaromír , Nečas David , Vrbka Martin , Velebný Vladimir , Huerta-Angeles Gloria
Published: September 2021

Hyaluronan (HA) is widely used for eye drops as lubricant to counteract dry eye disease. High and low molecular weight HA are currently used in ophthalmology. However, a large portion of the current literature on friction and lubrication addresses articular (joint) cartilage. Therefore, eye drops compositions based on HA and its derivatized forms are extensively characterized providing data on the tribological and mucoadhesive properties. The physiochemical properties are investigated in buffers used commonly in eye drops formulations. The tribological investigation reveals that amphiphilic HA-C12 decreases the friction coefficient. At the same time, the combination of trehalose/HA or HAC12 enhances up to eighty-fold the mucoadhesiveness. Thus, it is predicted a prolonged residence time on the surface of the eye. The incorporation of trehalose enhances the protection of human keratinocytes (HaCaT) cells, as demonstrated in an in-vitro cell-desiccation model. The presence of trehalose increases the friction coefficient. Medium molecular weight HA shows significantly lower friction coefficient than high molecular weight HA. This research represents a first, wide array of features of diverse HA forms for eye drops contributing to increase the knowledge of these preparations. The results here presented also provide valuable information for the design of highly performing HA-formulations addressing specific needs before preclinic.
Electrochemical N-Acetyl-β-D-glucosaminidase Urinalysis: Toward Sensor Chip-Based Diagnostics of Kidney Malfunction
Authors: Vibulcharoenkitja Piyanuch , Suginta Wipa , Schulte Albert
Published: September 2021

N-Acetyl-β-D-glucosaminidase (GlcNAcase) is a valuable biomarker for kidney health, as an increased urinary level of the enzyme indicates cell damage within the renal tubular filtration system from acute or chronic organ injury or exposure to nephrotoxic compounds. Effective renal function is vital for physiological homeostasis, and early detection of acute or chronic renal malfunction is critically important for timely treatment decisions. Here, we introduce a novel option for electrochemical urinalysis of GlcNAcase, based on anodic differential pulse voltammetry at boron-doped diamond disk sensors of the oxidizable product 4-nitrophenol (4NP), which is released by the action of GlcNAcase on the synthetic substrate 4NP-N-acetyl-β-D-glucosaminide (GlcNAc-4NP), added to the test solution as a reporter molecule. The proposed voltammetric enzyme activity screen accurately distinguishes urine samples of normal, slightly elevated and critically high urinary GlcNAcase content without interference from other urinary constituents. Moreover, this practice has the potential to be adapted for use in a hand-held device for application in clinical laboratories by physicians or in personal home health care. Evidence is also presented for the effective management of the procedure with mass-producible screen-printed sensor chip platforms.
Studies of Peculiar Mg-Containing and Oscillating Bioapatites in Sheep and Horse Teeth
Authors: Kuczumow Andrzej , Nowak Jakub , Chałas Renata , Ptasiewicz Maja , Siejak Przemysław , Jarzębski Maciej
Published: September 2021

New types of biological apatites have been discovered in molar sheep and horse teeth and are divided in two types. In the first and more general type, the release of Mg ions is parallel to the changes in composition of apatite leading to a final stoichiometric ratio of Ca to P ions, going from dentin depth towards the boundary of enamel with air. Inside dentin, another apatite sub-types were discovered with alternating layers of Mg-rich and C-rich apatites. The approximate formal stoichiometric relationships for these peculiar types of bioapatites are suggested. We identified two kinds of ion-exchanges responsible for formation of peculiar apatites. Various combinations of main and minor elements lead to new versions of biological apatites.
Novel Micro-Nano Optoelectronic Biosensor for Label-Free Real-Time Biofilm Monitoring
Authors: Brunetti Giuseppe , Conteduca Donato , Armenise Mario , Ciminelli Caterina
Published: September 2021

According to the World Health Organization forecasts, AntiMicrobial Resistance (AMR) is expected to become one of the leading causes of death worldwide in the following decades. The rising danger of AMR is caused by the overuse of antibiotics, which are becoming ineffective against many pathogens, particularly in the presence of bacterial biofilms. In this context, non-destructive label-free techniques for the real-time study of the biofilm generation and maturation, together with the analysis of the efficiency of antibiotics, are in high demand. Here, we propose the design of a novel optoelectronic device based on a dual array of interdigitated micro- and nanoelectrodes in parallel, aiming at monitoring the bacterial biofilm evolution by using optical and electrical measurements. The optical response given by the nanostructure, based on the Guided Mode Resonance effect with a Q-factor of about 400 and normalized resonance amplitude of about 0.8, allows high spatial resolution for the analysis of the interaction between planktonic bacteria distributed in small colonies and their role in the biofilm generation, calculating a resonance wavelength shift variation of 0.9 nm in the presence of bacteria on the surface, while the electrical response with both micro- and nanoelectrodes is necessary for the study of the metabolic state of the bacteria to reveal the efficacy of antibiotics for the destruction of the biofilm, measuring a current change of 330 nA when a 15 µm thick biofilm is destroyed with respect to the absence of biofilm.
Neonatal Seizures: An Overview of Genetic Causes and Treatment Options
Authors: Spoto Giulia , Saia Maria Concetta , Amore Greta , Gitto Eloisa , Loddo Giuseppe , Mainieri Greta , Nicotera Antonio Gennaro , Di Rosa Gabriella
Published: September 2021

Seizures are the most frequent neurological clinical symptoms of the central nervous system (CNS) during the neonatal period. Neonatal seizures may be ascribed to an acute event or symptomatic conditions determined by genetic, metabolic or structural causes, outlining the so-called ‘Neonatal Epilepsies’. To date, three main groups of neonatal epilepsies are recognised during the neonatal period: benign familial neonatal epilepsy (BFNE), early myoclonic encephalopathy (EME) and ‘Ohtahara syndrome’ (OS). Recent advances showed the role of several genes in the pathogenesis of these conditions, such as KCNQ2, KCNQ3, ARX, STXBP1, SLC25A22, CDKL5, KCNT1, SCN2A and SCN8A. Herein, we reviewed the current knowledge regarding the pathogenic variants most frequently associated with neonatal seizures, which should be considered when approaching newborns affected by these disorders. In addition, we considered the new possible therapeutic strategies reported in these conditions.
Odor Identification and Regional Gray Matter Atrophy in Patients with Alzheimer’s Disease, Parkinson’s Disease, and the Healthy Elderly: A Cross-Sectional Structural MRI Study
Authors: Jesmanas Simonas , Gleiznienė Rymantė , Baranauskas Mindaugas , Matijošaitis Vaidas , Rastenytė Daiva
Published: September 2021

Multiple associations between impaired olfactory performance and regional cortical and deep gray matter atrophy have been reported in separate studies of patients with Alzheimer’s disease (AD), Parkinson’s disease (PD), and of the healthy elderly. We aimed to evaluate such possible associations among these populations in a unified manner. Twenty AD, twenty PD patients’ and twenty healthy age- and sex-matched controls’ odor identification performance was assessed with the Lithuanian adaptation of the Sniffin’ Sticks 12 odor identification test, followed by morphometric gray matter analysis by MRI using FreeSurfer. AD patients had significantly lower cognitive performance than both PD patients and the healthy elderly, as evaluated with the Mini-Mental State Examination (MMSE). Odor identification performance was significantly worse in AD and PD patients compared with the healthy elderly; AD patients performed slightly worse than PD patients, but the difference was not statistically significant. Among patients with AD, worse odor identification performance was initially correlated with atrophy of multiple cortical and deep gray matter regions known to be involved in olfactory processing, however, only two measures—decreased thicknesses of the right medial and left lateral orbitofrontal cortices—remained significant after adjustment for possible confounders (age, MMSE score, and global cortical thickness). Among patients with PD and the healthy elderly we found no similar statistically significant correlations. Our findings support the key role of the orbitofrontal cortex in odor identification among patients with AD, and suggest that correlations between impaired odor identification performance and regional gray matter atrophy may be relatively more pronounced in AD rather than in PD.
HPA Axis in the Pathomechanism of Depression and Schizophrenia: New Therapeutic Strategies Based on Its Participation
Authors: Mikulska Joanna , Juszczyk Gabriela , Gawrońska-Grzywacz Monika , Herbet Mariola
Published: September 2021

The hypothalamic-pituitary-adrenal (HPA) axis is involved in the pathophysiology of many neuropsychiatric disorders. Increased HPA axis activity can be observed during chronic stress, which plays a key role in the pathophysiology of depression. Overactivity of the HPA axis occurs in major depressive disorder (MDD), leading to cognitive dysfunction and reduced mood. There is also a correlation between the HPA axis activation and gut microbiota, which has a significant impact on the development of MDD. It is believed that the gut microbiota can influence the HPA axis function through the activity of cytokines, prostaglandins, or bacterial antigens of various microbial species. The activity of the HPA axis in schizophrenia varies and depends mainly on the severity of the disease. This review summarizes the involvement of the HPA axis in the pathogenesis of neuropsychiatric disorders, focusing on major depression and schizophrenia, and highlights a possible correlation between these conditions. Although many effective antidepressants are available, a large proportion of patients do not respond to initial treatment. This review also discusses new therapeutic strategies that affect the HPA axis, such as glucocorticoid receptor (GR) antagonists, vasopressin V1B receptor antagonists and non-psychoactive CB1 receptor agonists in depression and/or schizophrenia.
Glial PAMPering and DAMPening of Adult Hippocampal Neurogenesis
Authors: Parkitny Luke , Maletic-Savatic Mirjana
Published: September 2021

Adult neurogenesis represents a mature brain’s capacity to integrate newly generated neurons into functional circuits. Impairment of neurogenesis contributes to the pathophysiology of various mood and cognitive disorders such as depression and Alzheimer’s Disease. The hippocampal neurogenic niche hosts neural progenitors, glia, and vasculature, which all respond to intrinsic and environmental cues, helping determine their current state and ultimate fate. In this article we focus on the major immune communication pathways and mechanisms through which glial cells sense, interact with, and modulate the neurogenic niche. We pay particular attention to those related to the sensing of and response to innate immune danger signals. Receptors for danger signals were first discovered as a critical component of the innate immune system response to pathogens but are now also recognized to play a crucial role in modulating non-pathogenic sterile inflammation. In the neurogenic niche, viable, stressed, apoptotic, and dying cells can activate danger responses in neuroimmune cells, resulting in neuroprotection or neurotoxicity. Through these mechanisms glial cells can influence hippocampal stem cell fate, survival, neuronal maturation, and integration. Depending on the context, such responses may be appropriate and on-target, as in the case of learning-associated synaptic pruning, or excessive and off-target, as in neurodegenerative disorders.
Towards a Comprehensive Account of Rhythm Processing Issues in Developmental Dyslexia
Authors: Rathcke Tamara , Lin Chia-Yuan
Published: September 2021

Developmental dyslexia is typically defined as a difficulty with an individual’s command of written language, arising from deficits in phonological awareness. However, motor entrainment difficulties in non-linguistic synchronization and time-keeping tasks have also been reported. Such findings gave rise to proposals of an underlying rhythm processing deficit in dyslexia, even though to date, evidence for impaired motor entrainment with the rhythm of natural speech is rather scarce, and the role of speech rhythm in phonological awareness is unclear. The present study aimed to fill these gaps. Dyslexic adults and age-matched control participants with variable levels of previous music training completed a series of experimental tasks assessing phoneme processing, rhythm perception, and motor entrainment abilities. In a rhythm entrainment task, participants tapped along to the perceived beat of natural spoken sentences. In a phoneme processing task, participants monitored for sonorant and obstruent phonemes embedded in nonsense strings. Individual sensorimotor skills were assessed using a number of screening tests. The results lacked evidence for a motor impairment or a general motor entrainment difficulty in dyslexia, at least among adult participants of the study. Instead, the results showed that the participants’ performance in the phonemic task was predictive of their performance in the rhythmic task, but not vice versa, suggesting that atypical rhythm processing in dyslexia may be the consequence, but not the cause, of dyslexic difficulties with phoneme-level encoding. No evidence for a deficit in the entrainment to the syllable rate in dyslexic adults was found. Rather, metrically weak syllables were significantly less often at the center of rhythmic attention in dyslexic adults as compared to neurotypical controls, with an increased tendency in musically trained participants. This finding could not be explained by an auditory deficit in the processing of acoustic-prosodic cues to the rhythm structure, but it is likely to be related to the well-documented auditory short-term memory issue in dyslexia.
Adaptation Strategies of Residential Buildings Based on a Health Risk Evaluation—A Case Study of Townhouses in Taiwan
Authors: Tsay Yaw-Shyan , Tang Chen , Lu Mei-Chen
Published: September 2021

Global warming increases the probability of extreme events and heat waves triggering severe impacts on human health, especially the elderly. Taiwan is an aged society, so residential buildings, which cannot withstand extreme temperature events, increase the risk of harm for the elderly. Furthermore, Taiwanese prefer to open the windows to reduce indoor high temperatures, which causes high levels of outdoor PM2.5 to flow indoors, leading to health risks. Therefore, this research proposes a strategy to create a house with a low temperature and a low PM2.5 health risk for the elderly based on building envelope renovation and windows user behavior patterns. The risk day is demonstrated as an index to evaluate the indoor environment quality, which is based on the number of days that exceed the health risk threshold. The results show that the performance improvement of the building envelope and control of the window opening timing can effectively reduce the risk days by 48.5%. This means that passive strategies cannot fully control health risks, and the use of equipment is necessary. Finally, if the current situation is maintained without any adjustment or strategy improvement, an additional 41.3% energy consumption must be paid every year to control health risks.
Anti-PD-1/Anti-PD-L1 Drugs and Radiation Therapy: Combinations and Optimization Strategies
Authors: Boustani Jihane , Lecoester Benoît , Baude Jérémy , Latour Charlène , Adotevi Olivier , Mirjolet Céline , Truc Gilles
Published: September 2021

Immune checkpoint inhibitors have been associated with long-term complete responses leading to improved overall survival in several cancer types. However, these novel immunotherapies are only effective in a small proportion of patients, and therapeutic resistance represents a major limitation in clinical practice. As with chemotherapy, there is substantial evidence that radiation therapy promotes anti-tumor immune responses that can enhance systemic responses to immune checkpoint inhibitors. In this review, we discuss the main preclinical and clinical evidence on strategies that can lead to an enhanced response to PD-1/PD-L1 blockade in combination with radiation therapy. We focused on central issues in optimizing radiation therapy, such as the optimal dose and fractionation for improving the therapeutic ratio, as well as the impact on immune and clinical responses of dose rate, target volume, lymph nodes irradiation, and type of radiation particle. We explored the addition of a third immunomodulatory agent to the combination such as other checkpoint inhibitors, chemotherapy, and treatment targeting the tumor microenvironment components. The strategies described in this review provide a lead for future clinical trials.
Circulating and Intracellular miRNAs as Prognostic and Predictive Factors in HER2-Positive Early Breast Cancer Treated with Neoadjuvant Chemotherapy: A Review of the Literature
Authors: Isca Chrystel , Piacentini Federico , Mastrolia Ilenia , Masciale Valentina , Caggia Federica , Toss Angela , Piombino Claudia , Moscetti Luca , Barbolini Monica , Maur Michela , Dominici Massimo , Omarini Claudia
Published: September 2021

MicroRNAs (miRNA) are small noncoding RNAs that can act as both oncogene and tumor suppressors. Deregulated miRNA expression has been detected in human cancers, including breast cancer (BC). Considering their important roles in tumorigenesis, miRNAs have been investigated as potential prognostic and diagnostic biomarkers. Neoadjuvant setting is an optimal model to investigate in vivo the mechanism of treatment resistance. In the management of human epidermal growth factor receptor-2 (HER2)-positive early BC, the anti-HER2-targeted therapies have drastically changed the survival outcomes. Despite this, growing drug resistance due to the pressure of therapy is relatively frequent. In the present review, we focused on the main miRNAs involved in HER2-positive BC tumorigenesis and discussed the recent evidence on their predictive and prognostic value.
Evaluation of Comprehensive Gene Expression and NK Cell-Mediated Killing in Glioblastoma Cell Line-Derived Spheroids
Authors: Morimoto Takayuki , Nakazawa Tsutomu , Matsuda Ryosuke , Nishimura Fumihiko , Nakamura Mitsutoshi , Yamada Shuichi , Nakagawa Ichiro , Park Young-Soo , Tsujimura Takahiro , Nakase Hiroyuki
Published: September 2021

Glioblastoma (GBM) is the most common and aggressive primary brain tumor, with a dismal prognosis. Natural killer (NK) cells are large granular lymphocytes with natural cytotoxicity against tumor cells, and they should be established for the novel treatment of patients with GBM. We previously reported highly activated, and ex vivo-expanded NK cells derived from human peripheral blood, designated genuine induced NK cells (GiNK), which were induced by specific culture conditions and which exerted a cytotoxic effect on GBM cells via apoptosis. Here, we comprehensively summarize the molecular characteristics, especially focusing on the expression of stem cell markers, extracellular matrix markers, chemokines, chemokine receptors, and NK receptor ligands of spheroids derived from GBM cell lines as compared with that of two-dimensional (2D) adherent GBM cells via microarray. The spheroid had upregulated gene expression of stem cell markers, extracellular matrix markers, chemokines, chemokine receptors, and NK cell inhibitory receptor ligands compared with the 2D adherent GBM cells. Preclinical evaluation of the NK cells was performed via an ex vivo 3D spheroid model derived from GBM cell lines. In the model, the NK cells accumulated and infiltrated around the spheroids and induced GBM cell death. Flow cytometry-based apoptosis detection clearly showed that the NK cells induced GBM cell death via apoptosis. Our findings could provide pivotal information for NK cell-based immunotherapy for patients with GBM.
Validation of Four Thyroid Ultrasound Risk Stratification Systems in Patients with Hashimoto’s Thyroiditis; Impact of Changes in the Threshold for Nodule’s Shape Criterion
Authors: Słowińska-Klencka Dorota , Klencki Mariusz , Wojtaszek-Nowicka Martyna , Wysocka-Konieczna Kamila , Woźniak-Oseła Ewa , Popowicz Bożena
Published: September 2021

The aim of the study was to validate thyroid US malignancy features, especially the nodule’s shape, and selected Thyroid Imaging Reporting and Data Systems (EU-TIRADS; K-TIRADS; ACR-TIRADS, ATA guidelines) in patients with or without Hashimoto’s thyroiditis (HT and non-HT groups). The study included 1188 nodules (HT: 358, non-HT: 830) with known final diagnoses. We found that the strongest indications of nodule’s malignancy were microcalcifications (OR: 22.7) in HT group and irregular margins (OR:13.8) in non-HT group. Solid echostructure and macrocalcifications were ineffective in patients with HT. The highest accuracy of nodule’s shape criterion was noted on transverse section, with the cut-off value of anteroposterior to transverse dimension ratio (AP/T) close to 1.15 in both groups. When round nodules were regarded as suspicious in patients with HT (the cut-off value of AP/T set to ≥1), it led to a three-fold increase in sensitivity of this feature, with a disproportionally lower decrease in specificity and similar accuracy. Such a modification was effective also for cancers other than PTC. The diagnostic effectiveness of analyzed TIRADS in patients with HT and without HT was similar. Changes in the threshold for AP/T ratio influenced the number of nodules classified into the category of the highest risk, especially in the case of EU-TIRADS.
UBE2M Drives Hepatocellular Cancer Progression as a p53 Negative Regulator by Binding to MDM2 and Ribosomal Protein L11
Authors: Kim Ju-Ha , Jung Ji Hoon , Lee Hyo-Jung , Sim Deok-Yong , Im Eunji , Park Jieon , Park Woon-Yi , Ahn Chi-Hoon , Shim Bum-Sang , Kim Bonglee , Kim Sung-Hoon
Published: September 2021

Though UBE2M, an E2 NEDD8-conjugating enzyme, is overexpressed in HepG2, Hep3B, Huh7 and PLC/PRF5 HCCs with poor prognosis by human tissue array and TCGA analysis, its underlying oncogenic mechanism remains unclear. Herein, UBE2M depletion suppressed viability and proliferation and induced cell cycle arrest and apoptosis via cleavages of PARP and caspase 3 and upregulation of p53, Bax and PUMA in HepG2, Huh7 and Hep3B cells. Furthermore, UBE2M depletion activated p53 expression and stability, while the ectopic expression of UBE2M disturbed p53 activation and enhanced degradation of exogenous p53 mediated by MDM2 in HepG2 cells. Interestingly, UBE2M binds to MDM2 or ribosomal protein L11, but not p53 in HepG2 cells, despite crosstalk between p53 and UBE2M. Consistently, the colocalization between UBE2M and MDM2 was observed by immunofluorescence. Notably, L11 was required in p53 activation by UBE2M depletion. Furthermore, UBE2M depletion retarded the growth of HepG2 cells in athymic nude mice along with elevated p53. Overall, these findings suggest that UBE2M promotes cancer progression as a p53 negative regulator by binding to MDM2 and ribosomal protein L11 in HCCs.
Remodeling the Tumor Myeloid Landscape to Enhance Antitumor Antibody Immunotherapies
Authors: Hussain Khiyam , Cragg Mark S. , Beers Stephen A.
Published: September 2021

Among the diverse tumor resident immune cell types, tumor-associated macrophages (TAMs) are often the most abundant, possess an anti-inflammatory phenotype, orchestrate tumor immune evasion and are frequently associated with poor prognosis. However, TAMs can also be harnessed to destroy antibody-opsonized tumor cells through the process of antibody-dependent cellular phagocytosis (ADCP). Clinically important tumor-targeting monoclonal antibodies (mAb) such as Rituximab, Herceptin and Cetuximab, function, at least in part, by inducing macrophages to eliminate tumor cells via ADCP. For IgG mAb, this is mediated by antibody-binding activating Fc gamma receptors (FcγR), with resultant phagocytic activity impacted by the level of co-engagement with the single inhibitory FcγRIIb. Approaches to enhance ADCP in the tumor microenvironment include the repolarization of TAMs to proinflammatory phenotypes or the direct augmentation of ADCP by targeting so-called ‘phagocytosis checkpoints’. Here we review the most promising new strategies targeting the cell surface molecules present on TAMs, which include the inhibition of ‘don’t eat me signals’ or targeting immunostimulatory pathways with agonistic mAb and small molecules to augment tumor-targeting mAb immunotherapies and overcome therapeutic resistance.
Line-Field Confocal Optical Coherence Tomography May Enhance Monitoring of Superficial Basal Cell Carcinoma Treated with Imiquimod 5% Cream: A Pilot Study
Authors: Verzì Anna Elisa , Micali Giuseppe , Lacarrubba Francesco
Published: September 2021

Line-field confocal optical coherence tomography (LC-OCT) is a novel, non-invasive technique for real-time skin imaging. Imiquimod (IQ) 5% cream is an immune response modifier currently approved for the treatment of small, superficial basal cell carcinoma (BCC). The aim of this study was to investigate if LC-OCT may be useful to enhance the treatment monitoring of BCC. Twenty superficial BCCs from 12 patients were treated with IQ 5% cream once daily, five days a week, for six weeks. Clinical and LC-OCT evaluations were performed at baseline and 4 weeks after the end of treatment. At the end of the study, 13 lesions showed a complete clinical and LC-OCT response, 4 lesions a partial clinical and LC-OCT response, and 3 lesions a complete clinical response but residual tumoral signs at LC-OCT. Our pilot study suggests that LC-OCT may represent a promising tool able to enhance the evaluation of the treatment response of BCCs to non-invasive treatments. In our case series, its use highlighted, through a detailed, fast, and complete examination of the treated area, three cases of residual BCC that otherwise would have gone undetected at clinical examination. Future studies on larger series of patients treated with different modalities and with a longer follow-up are advisable.
Etiologies of Melanoma Development and Prevention Measures: A Review of the Current Evidence
Authors: Djavid Amir Reza , Stonesifer Connor , Fullerton Benjamin T. , Wang Samuel W. , Tartaro Marlene A. , Kwinta Bradley D. , Grimes Joseph M. , Geskin Larisa J. , Saenger Yvonne M.
Published: September 2021

(1) Melanoma is the most aggressive dermatologic malignancy, with an estimated 106,110 new cases to be diagnosed in 2021. The annual incidence rates continue to climb, which underscores the critical importance of improving the methods to prevent this disease. The interventions to assist with melanoma prevention vary and typically include measures such as UV avoidance and the use of protective clothing, sunscreen, and other chemopreventive agents. However, the evidence is mixed surrounding the use of these and other interventions. This review discusses the heritable etiologies underlying melanoma development before delving into the data surrounding the preventive methods highlighted above. (2) A comprehensive literature review was performed to identify the clinical trials, observational studies, and meta-analyses pertinent to melanoma prevention and incidence. Online resources were queried to identify epidemiologic and clinical trial information. (3) Evidence exists to support population-wide screening programs, the proper use of sunscreen, and community-targeted measures in the prevention of melanoma. Clinical evidence for the majority of the proposed preventive chemotherapeutics is presently minimal but continues to evolve. (4) Further study of these chemotherapeutics, as well as improvement of techniques in artificial intelligence and imaging techniques for melanoma screening, is warranted for continued improvement of melanoma prevention.
Lung Cancer Surgery after Treatment with Anti-PD1/PD-L1 Immunotherapy for Non-Small-Cell Lung Cancer: A Case—Cohort Study
Authors: El Husseini Kinan , Piton Nicolas , De Marchi Marielle , Grégoire Antoine , Vion Roman , Blavier Pierre , Thiberville Luc , Baste Jean-Marc , Guisier Florian
Published: September 2021

Background: Immune checkpoint inhibitors (ICIs) are the standard of care for non-resectable non-small-cell lung cancer and are under investigation for resectable disease. Some authors have reported difficulties during lung surgery following ICI treatment. This retrospective study investigated the perioperative outcomes of lung resection in patients with preoperative ICI. Methods: Patients with major lung resection after receiving ICIs were included as cases and were compared to patients who received preoperative chemotherapy without ICI. Surgical, clinical, and imaging data were collected. Results: A total of 25 patients were included in the ICI group, and 34 were included in the control group. The ICI patients received five (2–18) infusions of ICI (80% with pembrolizumab). Indications for surgery varied widely across groups (p < 0.01). Major pathological response was achieved in 44% of ICI patients and 23.5% of the control group (p = 0.049). Surgery reports showed a higher rate of tissue fibrosis/inflammation in the ICI group (p < 0.01), mostly in centrally located tumours (7/13, 53.8% vs. 3/11, 27.3% of distal tumours, p = 0.24), with no difference in operating time (p = 0.81) nor more conversions (p = 0.46) or perioperative complications (p = 0.94). There was no 90-day mortality. Disease-free survival was higher in the ICI group (HR = 0.30 (0.13–0.71), p = 0.02). Conclusions: This study further supports the safety and feasibility of lung resection in patients following preoperative treatment with ICI.
Machine Learning for Future Subtyping of the Tumor Microenvironment of Gastro-Esophageal Adenocarcinomas
Authors: Klein Sebastian , Duda Dan G.
Published: September 2021

Tumor progression involves an intricate interplay between malignant cells and their surrounding tumor microenvironment (TME) at specific sites. The TME is dynamic and is composed of stromal, parenchymal, and immune cells, which mediate cancer progression and therapy resistance. Evidence from preclinical and clinical studies revealed that TME targeting and reprogramming can be a promising approach to achieve anti-tumor effects in several cancers, including in GEA. Thus, it is of great interest to use modern technology to understand the relevant components of programming the TME. Here, we discuss the approach of machine learning, which recently gained increasing interest recently because of its ability to measure tumor parameters at the cellular level, reveal global features of relevance, and generate prognostic models. In this review, we discuss the relevant stromal composition of the TME in GEAs and discuss how they could be integrated. We also review the current progress in the application of machine learning in different medical disciplines that are relevant for the management and study of GEA.
Severe Late-Onset Grade III-IV Adverse Events under Immunotherapy: A Retrospective Study of 79 Cases
Authors: L’Orphelin Jean-Matthieu , Varey Emilie , Khammari Amir , Dreno Brigitte , Dompmartin Anne
Published: September 2021

Background: For several decades, PD-1 has been a target in malignant melanoma (MM). PD-1 inhibitors (nivolumab, pembrolizumab) and anti-CTLA-4 (CD152) (ipilimumab) have revolutionized cancer therapy. PD-1 and CTLA-4 inhibition leads to prolonged lymphocyte effects, which explains the cytotoxicity underlying immune-reaction-based adverse events (irAEs). Most irAEs occur in the first cycle of treatment at a median of 40 days. IrAEs of any grade have been observed in 68.2% of patients, with 10% of patients experiencing severe grade III/IV irAEs. Data on late-onset irAEs are lacking. Methods: Data on patients with advanced melanoma (N = 1862) from March 2016 to March 2021 were obtained from the RicMel database, a French national multicentric biobank dedicated to the follow-up of MM patients. Patients who received anti-PD-1 therapy or a combination therapy and experienced grade III-IV irAEs were selected and analyzed at 7 months, one year and two years after treatment was initiated. Results: Superficial spreading melanoma (SSM) and previous oncological drug administration before immunotherapy are significant risk factors for late-onset irAEs over 2 years after beginning immunotherapy in the univariate and multivariate analysis. The other parameters—sex, mutational status, association of immunotherapy (PD-1i and CTLA-4i) and overall response—were not significantly associated with late-onset irAEs. In our real-life data study, the median onset time of grade III-IV irAES was 128 days after the initiation of immune checkpoint inhibitors (ICI) therapy. Conclusions: Our study, using real-life data, suggests that patients with SSM and those who have received previous oncological treatments are more likely to experience late-onset grade III-IV irAES. Further multicentric studies with wider recruitment of patients should be performed to confirm our findings, potentially leading to changes in the recommended treatment for carefully monitored at-risk patients.
Efficacy and Safety of a Second Course of Stereotactic Radiation Therapy for Locally Recurrent Brain Metastases: A Systematic Review
Authors: Lucia François , Touati Ruben , Crainic Nicolae , Dissaux Gurvan , Pradier Olivier , Bourbonne Vincent , Schick Ulrike
Published: September 2021

Recent advances in cancer treatments have increased overall survival and consequently, local failures (LFs) after stereotactic radiotherapy/radiosurgery (SRS/SRT) have become more frequent. LF following SRS or SRT may be treated with a second course of SRS (SRS2) or SRT (SRT2). However, there is no consensus on whenever to consider reirradiation. A literature search was conducted according to PRISMA guidelines. Analysis included 13 studies: 329 patients (388 metastases) with a SRS2 and 135 patients (161 metastases) with a SRT2. The 1-year local control rate ranged from 46.5% to 88.3%. Factors leading to poorer LC were histology (melanoma) and lack of prior whole-brain radiation therapy, large tumor size and lower dose at SRS2/SRT2, poorer response at first SRS/SRT, poorer performance status, and no controlled extracranial disease. The rate of radionecrosis (RN) ranged from 2% to 36%. Patients who had a large tumor volume, higher dose and higher value of prescription isodose line at SRS2/SRT2, and large overlap between brain volume irradiated at SRS1/SRT1 and SRS2/SRT2 at doses of 18 and 12 Gy had a higher risk of developing RN. Prospective studies involving a larger number of patients are still needed to determine the best management of patients with local recurrence of brain metastases
Acesulfame K Photodegradation over Nitrogen-Doped TiO2
Authors: Pstrowska Katarzyna , Czapor-Irzabek Hanna , Borowiak Daniel , Burchacka Ewa
Published: September 2021

Acesulfame K is a zero-calorie alternative to sugar used worldwide. There is contradictory information on the toxicity of the compound, but its accumulation in the aquatic environment is undeniable. In this study, one-pot sol-gel synthesis was used to obtain nitrogen-doped TiO2 photocatalysts. Doping up to 6.29 wt % of nitrogen caused an increase in the surface area of the catalysts (48.55–58.23 m2∙g−1) and a reduction of the pHPZC value (5.72–5.05). Acesulfame K photodegradation was tested at the initial concentration of 20–100 ppm and the catalyst concentration at the level of 1 g∙L−1. Compared to the pure anatase, 4.83–6.29 wt % nitrogen-doped TiO2 showed an effective photodegradation of Acesulfame K. Ninety percent molecule removal was obtained after ~100 min, ~90 min, and ~80 min for initial concentrations of 20 ppm, 50 ppm, and 100 ppm, respectively. The increased activity of the catalysts is due to the modification of the TiO2 lattice structure and probably the limitation of the photogenerated electron/hole charge carrier recombination. It was shown that the electrostatic interactions between Acesulfame K and the catalyst surface play an important role in the photodegradation efficiency.
Improved Biocompatibility of TiO2 Nanotubes via Co-Precipitation Loading with Hydroxyapatite and Gentamicin
Authors: Tong Shuang , Sun Xu , Wu Anhua , Guo Shu , Zhang Hangzhou
Published: September 2021

The antibacterial properties of titanium make it useful for clinical applications. Hydroxyapatite (HA) is widely utilized as a coating on orthopedic implants to improve osteointegration. Titanium oxide nanotubes (TNT) are recognized as a promising solution for local antibiotic therapy in bone implants. It is demonstrated that the utilization of HA-coated titanium can improve the biocompatibility of bone implants. This research aims to examine the antibacterial properties and biocompatibility of the TiO2 nanotubes by loading HA and gentamicin. In vitro testing, the characterization of drug release, cell adhesion and proliferation, bacteria culture, and antibacterial tests were conducted. During the in vivo experiments, Staphylococcus aureus was implanted into the femur of rats. The animals were sacrificed at four weeks followed by microbiological and clinical assessments on the bone, which were conducted by removing the implants followed by agar plating. The in vitro cell incubation demonstrated that the TiO2 nanotubes loaded with hydroxyapatite and gentamicin had better cellular compatibility compared to Cp–Ti. In addition, in vitro elution testing showed that gentamicin was released from the hydroxyapatite/TiO2 nanotubes for as long as 22 days. The release time was much longer than the TNT loaded with gentamicin at only 6 h. All animals in the gentamicin/HA/TNT group were free of infection compared to those in the Cp–Ti, TNT, and HA/gentamicin/TNT groups. There was a considerable reduction in the rates of infection among the rats with gentamicin-HA-TNT coatings compared to standard titanium. These results indicated that the co-precipitation of gentamicin and HA loading using the TNT method provided a novel prophylactic method against prosthetic infections and other biomedical applications.
Sensitivity Enhancement in Plasma Polymer Films for Surface Acoustic Wave Based Sensor Applications
Authors: Avramov Ivan , Radeva Ekatherina , Lazarov Yuliyan , Grakov Teodor , Vergov Lazar
Published: September 2021

Plasma polymer films (PPF), widely used as sensing layers in surface acoustic wave (SAW) based gas and liquid phase sensors, have a major drawback: high concentrations of the sensed analytes easily drive these films into saturation, where accurate measurements are no longer possible. This work suggests a solution to this problem by modifying the PPF with the sensed chemical compound to improve the overall sorption properties and sensor dynamic range. Thin polymer films were synthesized from hexamethyldisiloxane (HMDSO) and triethylsilane (TES) monomers in a plasma-enhanced chemical vapor deposition (PECVD) process using a RF plasma reactor. We used these Si-containing compounds because they are known for their excellent sensing properties. In this work, the layers were deposited onto the active surface of high-Q 438 MHz Rayleigh SAW two-port resonators, used as mass sensitive sensor elements. We call these devices quartz surface microbalances (QSM). In a second step, ammonia plasma modification was applied to the HMDSO and TES films, in order to achieve a higher sensitivity to NH3. The sensors were probed at different NH3 gas concentrations in a computer controlled gas probing setup. A comparison with unmodified films revealed a 74% to 85% improvement in both the sensitivity and sorption ability of the HMDSO sensing layers, and of about 8% for the TES films.
Comparative Numerical Study of Thermal Features Analysis between Oldroyd-B Copper and Molybdenum Disulfide Nanoparticles in Engine-Oil-Based Nanofluids Flow
Authors: Shahzad Faisal , Jamshed Wasim , Ibrahim Rabha W. , Sooppy Nisar Kottakkaran , Qureshi Muhammad Amer , Hussain Syed M. , Mohamed Isa Siti Suzilliana Putri , Eid Mohamed R. , Abdel-Aty Abdel-Haleem , Yahia I. S.
Published: September 2021

Apart from the Buongiorno model, no effort was ably accomplished in the literature to investigate the effect of nanomaterials on the Oldroyd-B fluid model caused by an extendable sheet. This article introduces an innovative idea regarding the enforcement of the Tiwari and Das fluid model on the Oldroyd-B fluid (OBF) model by considering engine oil as a conventional base fluid. Tiwari and Das’s model takes into account the volume fraction of nanoparticles for heat transport enhancement compared to the Buongiorno model that depends significantly on thermophoresis and Brownian diffusion impacts for heat transport analysis. In this paper, the thermal characteristics of an Oldroyd-B nanofluid are reported. Firstly, the transformation technique is applied on partial differential equations from boundary-layer formulas to produce nonlinear ordinary differential equations. Subsequently, the Keller-box numerical system is utilized to obtain final numerical solutions. Copper engine oil (Cu–EO) and molybdenum disulfide engine oil (MoS2–EO) nanofluids are considered. From the whole numerical findings and under the same condition, the thermodynamic performance of MoS2–EO nanofluid is higher than that of Cu–EO nanofluid. The thermal efficiency of Cu–EO over MoS2–EO is observed between 1.9% and 43%. In addition, the role of the porous media parameter is to reduce the heat transport rate and to enhance the velocity variation. Finally, the impact of the numbers of Reynolds and Brinkman is to increase the entropy.
A Novel Phosphorescent Iridium(III) Complex Bearing Formamide for Quantitative Fluorine Anion Detection
Authors: Guo Song , Guo Chaoxiong , Lu Zhao , Du Linlin , Gao Man , Liu Shujuan , Liu Yuanli , Zhao Qiang
Published: September 2021

Fluorine anion plays a critical role for human health, especially for the teeth and the skeletal system, and a deficiency or excess of fluorine anion will result in various diseases. Thus, the accurate and timely detection of fluorine content is of great importance. Herein, a novel and sensitive fluorine probe based on ionic iridium(III) complex using 5-formamide phenanthroline as an ancillary ligand was designed and synthesized rationally. The probe exhibited excellent performance for F− detection in organic solvents. H-bonding between the fluoride and the amide proton was formed, thus changing the photophysical properties of the probe and leading to significant phosphorescence quenching. Nuclear magnetic resonance titration and theoretical calculations were carried out to understand the mechanism in detail. This is the first report of an iridium(III) complex probe for F− detection based on the interaction between formamide and fluorine anion.
Modeling the Stress-Induced Transformation Behavior of Shape Memory Alloys under Multiaxial Loading Conditions
Authors: Chen Lei , Zhang Hongying , Song Mitao , Yue Xinxin , Zhang Jian
Published: September 2021

A large number of criteria to model the onset of plasticity for ductile metals have been proposed by researchers in the last century. Strangely, very few researchers have tried to model the stress-induced crystalline phase transformation of Shape Memory Alloys (SMAs) according to yield criteria. This paper focuses on the question: is a yield criterion originally proposed for describing the plastic behavior of metals suitable to model the “pseudoelastic” behavior of SMAs? To answer this question, two yield criteria originally proposed by the present author are used to predict the initial surface of transformation onset of two different SMAs: Cu-Al-Be and Ni-Ti alloy. The predicted initial transformation onset surfaces of the two SMAs are compared with experimental results and existing theories reported in the literature and some significant conclusions and recommendations are given.