bluuebunny/crossref_metadata_2025 huggingface dataset:
Physical Modeling of Positive Multistrike Lightning Formation
Authors: Lysov Nikolay , Temnikov Alexander , Chernensky Leonid , Belova Olga , Orlov Alexander , Kivshar Tatiana , Kovalev Dmitry , Zhuikov Anton
Published: December 2022

The first results of the physical modeling of positive multistrike lightning formation processes using positively charged artificial thunderstorm cells are presented. Experimental studies have shown a significant influence of the number of thunderstorm cells and groups of model hydrometeors introduced into them on the probability of the initiation of repeated strikes. It was found that with an increased number of cells and groups of model hydrometeors, the probability of the formation of repeated positive discharges increases several times. When the second group of model hydrometeors has been introduced into the artificial thunderstorm cell, or when the number of cells has been increased, the probability of the repeated discharge initiation has increased almost in three and in four times respectively. It has been revealed that, depending on the arrangement of model hydrometeor groups in artificial thundercloud cells, the formation of repeated positive discharges from them may proceed both with the “connection” of the uncharged areas of the lower cell and with the “connection” of the upper cell. The parameters of the first and repeated impulse current pulses between the positively charged cells and the ground were determined. It was found that with an increasing number of model hydrometeor groups, the value of the charge neutralized during the stages of first and repeated discharge formation increases. When forming multistrike positive discharges with the “connection” of the upper artificial thunderstorm cell, 20–30% more cloud charge has been neutralized during the repeated discharge than during the formation of a single positive discharge. It was found that the formation of positive repeated discharges was observed in about half of the cases, and that the radiation power and impulse current amplitude at repeated discharges are higher than at the first discharge. This article discusses some possible reasons for such a ratio between the parameters of the first and repeated discharges. It is assumed that the discovered significant influence of large model hydrometeor groups on the probability of the formation and the characteristics of repeated positive discharges from artificial thunderstorm cells indicate a possible key influence of hail arrays in the thundercloud on the formation of repeated strikes of positive lightning and bipolar lightning. The obtained results show that artificial thunderstorm cells of positive polarity, together with groups of large model hydrometeors, have prospects for physical modeling and the investigation of processes of the formation of positive and bipolar repeated lightning strikes.
Higher-Order Recombination Processes in Argon Ions Observed via X-ray Emission in an EBIT
Authors: Biela-Nowaczyk Weronika , Amaro Pedro , Grilo Filipe , Warczak Andrzej
Published: December 2022

In electron–ion collisions, recombination processes play a very important role. Recently, multielectron recombination processes have been highly investigated, as they carry information about electron–electron interaction. Among them, the most basic process is dielectronic recombination (DR). The research presented here was conducted using an EBIT at Jagiellonian University. Using X-ray spectroscopy, we conducted research into K-LL, K-LM, K-LN, K-LO and K-MM resonances. The aim of this study was to investigate the contribution of the intershell higher-order recombination processes in collected spectra. A good resolution for the K-LL DR spectrum made it possible to distinguish structures for He- up to C-like Ar ions.
Cochlear Implantation Following Transcanal Infrapromontorial Approach for Vestibular Schwannoma: A Case Series
Authors: Dallari Virginia , Apa Enrico , Monzani Daniele , Genovese Elisabetta , Marchioni Daniele , Soloperto Davide , Sacchetto Luca
Published: December 2022

Background: Cochlear implantation (CI) following endoscopic transcanal infrapromontorial vestibular schwannoma (VS) dissection is a feasible intervention in intracanalicular VS, with minimal extension into the cerebellopontine angle, but no audiologic results have ever been reported in the literature. Methods: From 2015 to 2021 in the Otorhynolaryngology Departments of Modena and Verona, three patients underwent this intervention. All were suffering from sporadic left-sided intracanalicular Koos I VS. Intraoperative electrically evoked auditory brainstem responses and electrophysiological measurements were performed before and after the placement of the electrode array, respectively. Since device activation one month after the surgery, each patient was followed up with audiometric tests, data logging, electrode impedance measurements and neural response telemetry performed at each scheduled fitting session at 15 days and 3, 6, 12 and 24 months. Results: Only in patient No. 3, an auditory benefit was observed and still evident even 36 months after activation. Impedances increased progressively in patient No. 1 and a benefit was never reported. Patient No. 2 left the follow-up for worsening comorbidities. Conclusions: CI following transcanal infrapromontorial VS resection is a beneficial intervention. The residual cochlear nerve after the tumour dissection and the course of electrophysiological measurements in the postoperative period were the main predictive factors for audiological outcomes.
Unfolding a Hidden Lagrangian Structure of a Class of Evolution Equations
Authors: Rosenau Philip
Published: December 2022

It is shown that a simple modification of the standard Lagrangian underlying the dynamics of Newtonian lattices enables one to infer the hidden Lagrangian structure of certain classes of first order in time evolution equations which lack the conventional Lagrangian structure. Implication to other setups is outlined and exemplified.
Chain-Engineering-Based De Novo Drug Design against MPXVgp169 Virulent Protein of Monkeypox Virus: A Molecular Modification Approach
Authors: Naveed Muhammad , Shabbir Muhammad Aqib , Ain Noor-ul , Javed Khushbakht , Mahmood Sarmad , Aziz Tariq , Khan Ayaz Ali , Nabi Ghulam , Shahzad Muhammad , Alharbi Mousa Essa , Alharbi Metab , Alshammari Abdulrahman
Published: December 2022

The unexpected appearance of the monkeypox virus and the extensive geographic dispersal of cases have prompted researchers to concentrate on potential therapeutic approaches. In addition to its vaccine build techniques, there should be some multiple integrated antiviral active compounds because of the MPV (monkeypox virus) outbreak in 2022. This study offers a computational engineering-based de novo drug discovery mediated by random antiviral active compounds that were screened against the virulent protein MPXVgp169, as one of the key players directing the pathogenesis of the virus. The screening of these candidates was supported by the use of 72 antiviral active compounds. The top candidate with the lowest binding affinity was selected for the engineering of chains or atoms. Literature assisted to identify toxic chains or atoms that were impeding the stability and effectiveness of antiviral compounds to modify them for enhanced efficacy. With a binding affinity of −9.4 Kcal/mol after chain, the lipophilicity of 0.41, the water solubility of 2.51 as soluble, and synthetic accessibility of 6.6, chain-engineered dolutegravir was one of the best active compounds, as proved by the computational engineering analysis. This study will revolutionize the era of drug engineering as a potential therapeutic strategy for monkeypox infection.
MITF Contributes to the Body Color Differentiation of Sea Cucumbers Apostichopus japonicus through Expression Differences and Regulation of Downstream Genes
Authors: Xing Lili , Liu Shilin , Zhang Libin , Yang Hongsheng , Sun Lina
Published: December 2022

Melanin, which is a pigment produced in melanocytes, is an important contributor to sea cucumber body color. MITF is one of the most critical genes in melanocyte development and melanin synthesis pathways. However, how MITF regulates body color and differentiation in sea cucumbers is poorly understood. In this study, we analyzed the expression level and location of MITF in white, purple, and green sea cucumbers and identified the genes regulated by MITF using chromatin immunoprecipitation followed by sequencing. The mRNA and protein expression levels of MITF were all highest in purple morphs and lowest in white morphs. In situ hybridization indicated that MITF mRNA were mainly expressed in the epidermis. We also identified 984, 732, and 1191 peaks of MITF binding in green, purple, and white sea cucumbers, which were associated with 727, 557, and 887 genes, respectively. Our findings suggested that MITF contributed to the body color differentiation of green, purple, and white sea cucumbers through expression differences and regulation of downstream genes. These results provided a basis for future studies to determine the mechanisms underlying body color formation and provided insights into gene regulation in sea cucumbers.
Genetic Diversity Evaluation and Conservation of Topmouth Culter (Culter alburnus) Germplasm in Five River Basins in China
Authors: He Miao , Fang Di-An , Chen Yong-jin , Sun Hai-bo , Luo Hui , Ren Ya-fei , Li Tian-you
Published: December 2022

To study the genetic diversity of Culter alburnus (C. alburnus) populations, we analyzed the genetic diversity of five C. alburnus populations from Songhua Lake (SH), Huaihe River (HH), Changjiang River (CJ), Taihu Lake (TH), and Gehu Lake (GH) based on mitochondrial COI gene sequences. The results showed that the average contents of bases T, C, A, and G in the 526 bp COI gene sequence were 25.3%, 18.1%, 28.1%, and 28.6%, respectively, which showed AT bias. A total of 115 polymorphic sites were detected in the five populations, and 11 haplotypes (Hap) were defined. The nucleotide diversity (Pi) of the five populations ranged from 0.00053 to 0.01834, and the haplotype diversity (Hd) ranged from 0.280 to 0.746, with the highest genetic diversity in the TH population, followed by the SH population, with lower genetic diversity in the HH, CJ and GH populations. The analysis of the fixation index (Fst) and the genetic distance between populations showed that there was significant genetic differentiation between the SH population and the other populations, and the genetic distances between all of them were far; the genetic diversity within populations was higher than that between populations. Neutral tests, mismatch distributions, and Bayesian skyline plot (BSP) analyses showed that the C. alburnus populations have not experienced population expansion and are relatively stable in historical dynamics.
Encouraging Tactics with Genetically Modified Probiotics to Improve Immunity for the Prevention of Immune-Related Diseases including Cardio-Metabolic Disorders
Authors: Asai Tomoko , Yoshikawa Sayuri , Ikeda Yuka , Taniguchi Kurumi , Sawamura Haruka , Tsuji Ai , Matsuda Satoru
Published: December 2022

The PI3K/AKT/mTOR signaling pathway may play crucial roles in the pathogenesis of obesity and diabetes mellitus, as well as metabolic syndromes, which could also be risk factors for cardio-metabolic disorders. Consistently, it has been shown that beneficial effects may be convoyed by the modulation of the PI3K/AKT/mTOR pathway against the development of these diseases. Importantly, the PI3K/AKT/mTOR signaling pathway can be modulated by probiotics. Probiotics have a variety of beneficial properties, with the potential of treating specific diseases such as immune-related diseases, which are valuable to human health. In addition, an increasing body of work in the literature emphasized the contribution of genetically modified probiotics. There now seems to be a turning point in the research of probiotics. A better understanding of the interactions between microbiota, lifestyle, and host factors such as genetics and/or epigenetics might lead to a novel therapeutic approach with probiotics for these diseases. This study might provide a theoretical reference for the development of genetically modified probiotics in health products and/or in functional foods for the treatment of cardio-metabolic disorders.
1-(Arylsulfonyl-isoindol-2-yl)piperazines as 5-HT6R Antagonists: Mechanochemical Synthesis, In Vitro Pharmacological Properties and Glioprotective Activity
Authors: Canale Vittorio , Trybała Wojciech , Chaumont-Dubel Séverine , Koczurkiewicz-Adamczyk Paulina , Satała Grzegorz , Bento Ophélie , Blicharz-Futera Klaudia , Bantreil Xavier , Pękala Elżbieta , Bojarski Andrzej J. , Lamaty Frédéric , Marin Philippe , Zajdel Paweł
Published: December 2022

In addition to the canonical Gs adenylyl cyclase pathway, the serotonin type 6 receptor (5-HT6R) recruits additional signaling pathways that control cognitive function, brain development, and synaptic plasticity in an agonist-dependent and independent manner. Considering that aberrant constitutive and agonist-induced active states are involved in various pathological mechanisms, the development of biased ligands with different functional profiles at specific 5-HT6R-elicited signaling pathways may provide a novel therapeutic perspective in the field of neurodegenerative and psychiatric diseases. Based on the structure of SB-258585, an inverse agonist at 5-HT6R-operated Gs and Cdk5 signaling, we designed a series of 1-(arylsulfonyl-isoindol-2-yl)piperazine derivatives and synthesized them using a sustainable mechanochemical method. We identified the safe and metabolically stable biased ligand 3g, which behaves as a neutral antagonist at the 5-HT6R-operated Gs signaling and displays inverse agonist activity at the Cdk5 pathway. Inversion of the sulfonamide bond combined with its incorporation into the isoindoline scaffold switched the functional profile of 3g at Gs signaling with no impact at the Cdk5 pathway. Compound 3g reduced the cytotoxicity of 6-OHDA and produced a glioprotective effect against rotenone-induced toxicity in C8-D1A astrocyte cell cultures. In view of these findings, compound 3g can be considered a promising biased ligand to investigate the role of the 5-HT6R-elicited Gs and Cdk5 signaling pathways in neurodegenerative diseases.
Metabolomics and a Breath Sensor Identify Acetone as a Biomarker for Heart Failure
Authors: Gladding Patrick , Cooper Maxine , Young Renee , Loader Suzanne , Smith Kevin , Zarate Erica , Green Saras , Villas Boas Silas , Shepherd Phillip , Kakadiya Purvi , Thorstensen Eric , Keven Christine , Coe Margaret , Jüllig Mia , Zhang Edmond , Schlegel Todd
Published: December 2022

Background: Multi-omics delivers more biological insight than targeted investigations. We applied multi-omics to patients with heart failure with reduced ejection fraction (HFrEF). Methods: 46 patients with HFrEF and 20 controls underwent metabolomic profiling, including liquid/gas chromatography mass spectrometry (LC-MS/GC-MS) and solid-phase microextraction (SPME) volatilomics in plasma and urine. HFrEF was defined using left ventricular global longitudinal strain, ejection fraction and NTproBNP. A consumer breath acetone (BrACE) sensor validated results in n = 73. Results: 28 metabolites were identified by GCMS, 35 by LCMS and 4 volatiles by SPME in plasma and urine. Alanine, aspartate and glutamate, citric acid cycle, arginine biosynthesis, glyoxylate and dicarboxylate metabolism were altered in HFrEF. Plasma acetone correlated with NT-proBNP (r = 0.59, 95% CI 0.4 to 0.7), 2-oxovaleric and cis-aconitic acid, involved with ketone metabolism and mitochondrial energetics. BrACE > 1.5 ppm discriminated HF from other cardiac pathology (AUC 0.8, 95% CI 0.61 to 0.92, p < 0.0001). Conclusion: Breath acetone discriminated HFrEF from other cardiac pathology using a consumer sensor, but was not cardiac specific.
The Relationship between the Oral Microbiota and Metabolic Syndrome
Authors: Prince Yvonne , Davison Glenda M. , Davids Saarah F. G. , Erasmus Rajiv T. , Kengne Andre P. , Graham Lisa M. , Raghubeer Shanel , Matsha Tandi E.
Published: December 2022

The oral microbiota plays a crucial role in both systemic inflammation and metabolic syndrome (MetS), which is characterised by low-grade inflammation. Studies have analysed the gut microbiota using stool specimens from subjects with MetS; however, the etiological role of the oral microbiota in the development of MetS is still uncertain. We investigated the oral microbiota of 128 subgingival plaque samples from a South African cohort with and without MetS. After a comprehensive analysis of the oral microbiota, we observed a significant increase in Gram-positive aerobic and anaerobic microbiota in those with MetS. We observed an abundance of Actinomyces, Corynebacterium, and Fusobacterium genera in the MetS group, which differed significantly from previous studies, which found Granulicatella to be enriched in MetS. To further assess the impact of the metabolic parameters (FBG, Waist C, HDL, TGs, and BP) on the oral microbiota, we calculated the odds ratio (ORs) for significant oral microbiota identified between the MetS groups. We found that different species were associated with at least four MetS risk factors. This study has shown that the oral microbiota is disrupted in MetS and may promote inflammation providing a gateway to other systemic diseases, including diabetes and cardiovascular diseases.
Heat Accumulation in Implant Inter-Osteotomy Areas—An Experimental In Vitro Study
Authors: Li Shanlin , Tanner Adam , Romanos Georgios , Delgado-Ruiz Rafael
Published: December 2022

To examine the influence of the distance between adjacent implant osteotomies on heat accumulation in the inter-osteotomy area, two experimental groups with 15 pairs of osteotomies in Type II polyurethane blocks were compared: 7 mm inter-osteotomy separations (Group A, n = 15) and 14 mm inter-osteotomy separations (Group B, n = 15). An infrared thermographic analysis of thermal changes in the inter-osteotomy area was completed. A one-way analysis of variance (ANOVA) and Fisher post-test were used to determine group differences. Higher temperatures were recorded in Group A at the coronal and middle levels compared to the apical level in both groups. The temperature reached max temperatures at T80s and T100s. In Group A, the threshold for thermal necrosis was exceeded. Meanwhile, Group B did not reach the threshold for thermal necrosis. Preparing adjacent implant osteotomies in dense bone with a 7 mm separation between their centers increases the temperature in the inter-osteotomy area, exceeding the threshold for bone thermal necrosis; meanwhile, increasing the distance between osteotomies reduces the thermal accumulation and the risk for thermal necrosis.
Vitamin D in Health and Disease
Authors: Murdaca Giuseppe , Gangemi Sebastiano
Published: December 2022

Vitamin D (VD) is a fat-soluble hormone that plays a fundamental role not only in calcium homeostasis and bone metabolism, but also has anti-inflammatory and antioxidant properties, acting on both innate and adaptive immunity [...]
Dynamic Changes of Brain Activity in Different Responsive Groups of Patients with Prolonged Disorders of Consciousness
Authors: Chen Chen , Han Jinying , Zheng Shuang , Zhang Xintong , Sun Haibo , Zhou Ting , Hu Shunyin , Yan Xiaoxiang , Wang Changqing , Wang Kai , Hu Yajuan
Published: December 2022

As medical technology continues to improve, many patients diagnosed with brain injury survive after treatments but are still in a coma. Further, multiple clinical studies have demonstrated recovery of consciousness after transcranial direct current stimulation. To identify possible neurophysiological mechanisms underlying disorders of consciousness (DOCs) improvement, we examined the changes in multiple resting-state EEG microstate parameters after high-definition transcranial direct current stimulation (HD-tDCS). Because the left dorsolateral prefrontal cortex is closely related to consciousness, it is often chosen as a stimulation target for tDCS treatment of DOCs. A total of 21 patients diagnosed with prolonged DOCs were included in this study, and EEG microstate analysis of resting state EEG datasets was performed on all patients before and after interventions. Each of them underwent 10 anodal tDCS sessions of the left dorsolateral prefrontal cortex over 5 consecutive working days. According to whether the clinical manifestations improved, DOCs patients were divided into the responsive (RE) group and the non-responsive (N-RE) group. The dynamic changes of resting state EEG microstate parameters were also analyzed. After multiple HD-tDCS interventions, the duration and coverage of class C microstates in the RE group were significantly increased. This study also found that the transition between microstates A and C increased, while the transition between microstates B and D decreased in the responsive group. However, these changes in EEG microstate parameters in the N-RE group have not been reported. Our findings suggest that EEG neural signatures have the potential to assess consciousness states and that improvement in the dynamics of brain activity was associated with the recovery of DOCs. This study extends our understanding of the neural mechanism of DOCs patients in consciousness recovery.
Effects of Transcranial Direct Current Stimulation Combined with Treadmill Training on Kinematics and Spatiotemporal Gait Variables in Stroke Survivors: A Randomized, Triple-Blind, Sham-Controlled Study
Authors: Dumont Arislander Jonathan Lopes , Cimolin Veronica , Parreira Rodolfo Borges , Armbrust Danilo , Fonseca Daniela Rosana Pedro , Fonseca Adriano Luís , Cordeiro Lorraine , Franco Renata Calhes , Duarte Natália Almeida Carvalho , Galli Manuela , Oliveira Cláudia Santos
Published: December 2022

The present study assessed the effects of anodal transcranial direct current stimulation (tDCS) combined with treadmill training on spatiotemporal and kinematic variables in stroke survivors using gait speed as the primary outcome. A randomized, sham-controlled, triple-blind, study was conducted involving 28 patients with hemiparesis allocated to two groups. The experimental group was submitted to treadmill training combined with anodal tDCS over the primary motor cortex (M1) of the damaged hemisphere. The control group was submitted to treadmill training combined with sham tDCS. Stimulation was administered (2 mA, 20 min) five times a week for two weeks during treadmill training. No significant differences (p > 0.05) in spatiotemporal variables were found in the intra-group and inter-group analyses. However, the experimental group demonstrated improvements in kinematic variables of the knee and ankle (p < 0.05) and these results were maintained one month after the end of the intervention. The inter-group analysis revealed significant differences (p < 0.05) with regard to the pelvis, hip and knee. Anodal tDCS over M1 of the damaged hemisphere combined with treadmill training did not affect spatiotemporal variables, but promoted improvements in kinematic variables of the pelvis, hip, knee and ankle and results were maintained one month after treatment.
Knowledge, Attitudes, and Practices towards COVID-19 among Pregnant Women in Northern Bangladesh: A Community-Based Cross-Sectional Study
Authors: Tasnim Homyra , Amin Md. Bony , Roy Nitai , Aktarujjaman Md. , Rogers Bryan T. , Rosby Raphyel , Hossain Ekhtear
Published: December 2022

Background: COVID-19, caused by SARS-CoV-2, remains a global public health concern despite the availability of effective antiviral treatment against multiple strains. Studies have shown that pregnant women are more susceptible to COVID-19 due to altered physiology and immunological features. Therefore, this study was designed to investigate pregnant women’s knowledge, attitudes, and practice (KAP) to prevent COVID-19 and determine the factors associated with KAP. Methods: A community-based cross-sectional study was conducted among 425 pregnant women in Northern Bangladesh. The samples were obtained using a simple random sampling technique from 5 April to 15 June 2020. The data were collected by face-to-face survey with a structured and pre-tested questionnaire and analyzed using SPSS version 25. Bivariable and multivariable logistic regression analyses were performed, and p-values < 0.05 at 95% CI were considered statistically significant. Results: Overall, the score of KAP among the respondents was 47.76%, 49.41%, and 56.24%, respectively. Participants’ area of residence, educational status of the husband, and antenatal care (ANC) visit were significantly associated with the level of knowledge, whereas age, educational status of the husband, number of living children, and knowledge were significant predictors of attitude. The knowledge of COVID-19 was the only predictor associated with the practice. Conclusion: Our study shows that almost half of the participants had poor knowledge, a negative attitude, and poor practices regarding COVID-19. Additional health education programs by healthcare professionals and different media, coordinated and combined efforts of government and individuals’ participation will be required to fight the spread of the infection.
Seismic Fragility of Aging Elevated Water Tank with Smooth Bars Considering Soil Structure Interaction
Authors: Rimal Hariram , Pradhan Piyush , Gautam Dipendra , Rupakhety Rajesh
Published: December 2022

The functionality of elevated water tanks is pivotal to assure after an earthquake as water supply is expected to be uninterrupted. Although elevated water tanks with deformed bars are widely studied, limited works exist for water tanks with smooth bars, although such tanks comprise a considerable fraction, even in the high seismic regions. To quantify the seismic vulnerability of aging elevated water tanks with smooth bars, we created analytical fragility functions for full, half, and empty reservoir conditions, considering fluid–structure and soil–structure interactions. The sum of findings reflects that soil flexibility and the amount of water present in the tank have a significant effect on overall seismic fragility, especially at higher damage states. The tanks are found to be most vulnerable when they are fully filled with water. The effect of soil flexibility is more pronounced at higher damage states. The difference between the fragility of flexible base and fixed base structures is found to increase with increasing ground motion intensity and it is the highest for the empty tank condition.
Dynamic Characteristic and Parameter Analysis of a Modular Building with Suspended Floors
Authors: He Qingguang , Zhang Shiquan , Shang Jiying
Published: December 2022

Over the past few years, modular buildings have become an important form of environmentally friendly architecture. Prefabricated construction methods have gained a lot of attention because they produce less construction waste and require less labor and water. However, the seismic performance of modular buildings needs to be improved. This paper proposes a prefabricated steel module with a suspended floor, which is based on a multi-tuned mass damped floor system. This paper also derives the form of a motion equation which is unified with the construction process of modular buildings, which can describe the change law of the mass, stiffness, and damping matrix of the structure in the processes of connecting the main structure with the suspended floor slab and of joining different floors. Since the performances of tuned mass damping devices are closely related to the dynamic characteristics of the structure, this paper uses ABAQUS for numerical analysis and mathematical induction (MI) to propose and verify a simplified method for calculating the lateral stiffness of the entire story from a single module’s lateral stiffness. Based on the principle of reducing the stiffness difference in the structure along different directions, a standard scheme of the horizontal extension of the module building is also specified. The results show that the simplified calculation method is reasonable and that the lateral stiffness of the structure increases linearly with the number of modules. Finally, the recommended values for the tuned frequency ratio and tuned damping ratio are given by investigating the dynamic response of the structure under Gaussian white noise excitation. The results show that the recommended tuning frequency ratio and damping ratio ranges in modular buildings are close to those for FIS buildings.
Causal Model Analysis of the Effect of Policy Formalism, COVID-19 Fear, Social Support and Work Stress on Construction Workers’ Anxiety during the Epidemic
Authors: Wu Tsung-Lin , Liu Hsiang-Te
Published: December 2022

This study mainly explores the impact of policy formalism, COVID-19 fear, social support, and work stress on the anxiety of construction workers during the epidemic. The main objective of this study is to incorporate formalism variables to explore their impact on the stress and anxiety of construction workers during the epidemic. In particular, the variable of formalism is changed from the variable of government bureaucracy to the cognition of “policy formalism” of the general public. This study intends to understand whether the gap between epidemic prevention regulations and practices affects the fear of construction site workers. A total of 743 construction site worker samples in the leisure industry were collected in this study, and the established hypotheses were tested using confirmatory factor analysis and structural equation modeling. The results of the study confirmed that during the COVID-19 outbreak, social support of site workers negatively affects anxiety; COVID-19 fear positively affects anxiety and work stress; work stress mediates the relationship between COVID-19 fear and anxiety; fear of infecting family members and fear of infecting self both positively affect anxiety; policy formalism positively affects fear of infecting family members and fear of infecting self.
Multimodal Treatment Strategies to Improve the Prognosis of Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma: A Narrative Review
Authors: Higuchi Tadashi , Shoji Yoshiaki , Koyanagi Kazuo , Tajima Kohei , Kanamori Kohei , Ogimi Mika , Yatabe Kentaro , Ninomiya Yamato , Yamamoto Miho , Kazuno Akihito , Nabeshima Kazuhito , Nakamura Kenji
Published: December 2022

Esophageal cancer is the seventh most common malignancy and sixth most common cause of cancer-related death globally. Esophageal squamous cell carcinoma (ESCC) with aortic or tracheal invasion is considered unresectable, and has an extremely poor prognosis; its standard treatment is definitive chemoradiotherapy (dCRT). In recent years, induction chemotherapy (ICT) has been reported to yield high response rates for locally advanced ESCC, and the efficacy and safety of ICT followed by conversion surgery (CS) have been investigated. Multimodal treatment, combining surgery with induction chemoradiotherapy (ICRT) or ICT, is necessary to improve ESCC prognosis. CS is generally performed for locally advanced ECC after ICRT or ICT when tumor downstaging is achieved, although its prognostic benefit remains controversial. The Japan Clinical Oncology Group (JCOG) has conducted a three-arm phase III randomized controlled trial (JCOG1510) to confirm the superiority of DCF (docetaxel, cisplatin, and 5-fluorouracil) ICT, over conventional dCRT, among patients with initially unresectable ESCC. In recent years, researchers have reported favorable outcomes of induction therapy followed by CS and salvage surgery, after dCRT or systemic immunochemotherapy. In this review, we will describe the latest developments in the multimodal treatment including chemotherapy, CRT, surgery, and immunotherapy, which may improve oncological and survival outcomes for patients with cT4 ESCC.
Dynamic Optical Coherence Tomography: A Non-Invasive Imaging Tool for the Distinction of Nevi and Melanomas
Authors: Perwein Maria Katharina Elisabeth , Welzel Julia , De Carvalho Nathalie , Pellacani Giovanni , Schuh Sandra
Published: December 2022

Along with the rising melanoma incidence in recent decades and bad prognoses resulting from late diagnoses, distinguishing between benign and malignant melanocytic lesions has become essential. Unclear cases may require the aid of non-invasive imaging to reduce unnecessary biopsies. This multicentric, case-control study evaluated the potential of dynamic optical coherence tomography (D-OCT) to identify distinguishing microvascular features in nevi. A total of 167 nevi, including dysplastic ones, on 130 participants of all ages and sexes were examined by D-OCT and dermoscopy with a histological reference. Three blinded analyzers evaluated the lesions. Then, we compared the features to those in 159 melanomas of a prior D-OCT study and determined if a differential diagnosis was possible. We identified specific microvascular features in nevi and a differential diagnosis of melanomas and nevi was achieved with excellent predictive values. We conclude that D-OCT overcomes OCT´s inability to distinguish melanocytic lesions based on its focus on microvascularization. To determine if an addition to the gold standard of a clinical-dermoscopic examination improves the diagnosis of unclear lesions, further studies, including a larger sample of dysplastic nevi and artificial intelligence, should be conducted.
Epidemiologic, Genetic, Pathogenic, Metabolic, Epigenetic Aspects Involved in NASH-HCC: Current Therapeutic Strategies
Authors: Gutiérrez-Cuevas Jorge , Lucano-Landeros Silvia , López-Cifuentes Daniel , Santos Arturo , Armendariz-Borunda Juan
Published: December 2022

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is the sixth most frequent cancer in the world, being the third cause of cancer-related deaths. Nonalcoholic steatohepatitis (NASH) is characterized by fatty infiltration, oxidative stress and necroinflammation of the liver, with or without fibrosis, which can progress to advanced liver fibrosis, cirrhosis and HCC. Obesity, metabolic syndrome, insulin resistance, and diabetes exacerbates the course of NASH, which elevate the risk of HCC. The growing prevalence of obesity are related with increasing incidence of NASH, which may play a growing role in HCC epidemiology worldwide. In addition, HCC initiation and progression is driven by reprogramming of metabolism, which indicates growing appreciation of metabolism in the pathogenesis of this disease. Although no specific preventive pharmacological treatments have recommended for NASH, dietary restriction and exercise are recommended. This review focuses on the molecular connections between HCC and NASH, including genetic and risk factors, highlighting the metabolic reprogramming and aberrant epigenetic alterations in the development of HCC in NASH. Current therapeutic aspects of NASH/HCC are also reviewed.
Utilization of Cancer Cell Line Screening to Elucidate the Anticancer Activity and Biological Pathways Related to the Ruthenium-Based Therapeutic BOLD-100
Authors: Park Brian J. , Raha Paromita , Pankovich Jim , Bazett Mark
Published: December 2022

BOLD-100 (sodium trans-[tetrachlorobis(1H indazole)ruthenate(III)]) is a ruthenium-based anticancer compound currently in clinical development. The identification of cancer types that show increased sensitivity towards BOLD-100 can lead to improved developmental strategies. Sensitivity profiling can also identify mechanisms of action that are pertinent for the bioactivity of complex therapeutics. Sensitivity to BOLD-100 was measured in a 319-cancer-cell line panel spanning 24 tissues. BOLD-100’s sensitivity profile showed variation across the tissue lineages, including increased response in esophageal, bladder, and hematologic cancers. Multiple cancers, including esophageal, bile duct and colon cancer, had higher relative response to BOLD-100 than to cisplatin. Response to BOLD-100 showed only moderate correlation to anticancer compounds in the Genomics of Drug Sensitivity in Cancer (GDSC) database, as well as no clear theme in bioactivity of correlated hits, suggesting that BOLD-100 may have a differentiated therapeutic profile. The genomic modalities of cancer cell lines were modeled against the BOLD-100 sensitivity profile, which revealed that genes related to ribosomal processes were associated with sensitivity to BOLD-100. Machine learning modeling of the sensitivity profile to BOLD-100 and gene expression data provided moderative predictive value. These findings provide further mechanistic understanding around BOLD-100 and support its development for additional cancer types.
Estimated Costs of the Ipilimumab–Nivolumab Therapy and Related Adverse Events in Metastatic Melanoma
Authors: Gautron Moura Bianca , Gerard Camille , Testart Nathalie , Caikovski Marian , Wicky Alexandre , Aedo-Lopez Veronica , Berthod Grégoire , Homicsko Krisztian , Prior John , Dromain Clarisse , Kandalaft Lana , Cuendet Michel , Michielin Olivier
Published: December 2022

Combined ipilimumab and nivolumab significantly improve outcomes in metastatic melanoma patients but bear an important financial impact on the healthcare system. Here, we analyze the treatment costs, focusing on irAE. We conducted a retrospective analysis of 62 melanoma patients treated with ipilimumab–nivolumab at the Lausanne University Hospital between 1 June 2016 and 31 August 2019. The frequency of irAEs and outcomes were evaluated. All melanoma-specific costs were analyzed from the first ipilimumab–nivolumab dose until the therapy given subsequently or death. A total of 54/62 (87%) patients presented at least one irAE, and 31/62 (50%) presented a grade 3–4 irAE. The majority of patients who had a complete response 12/14 (86%) and 21/28 (75%) of overall responders presented a grade 3–4 toxicity, and there were no responses in patients without toxicity. Toxicity costs represented only 3% of the total expenses per patient. The most significant contributions were medication costs (44%) and disease costs (39%), mainly disease-related hospitalization costs, not toxicity-related. Patients with a complete response had the lowest global median cost per week of follow up (EUR 2425) and patients who had progressive disease (PD), the highest one (EUR 8325). Except for one patient who had a Grade 5 toxicity (EUR 6043/week), we observe that less severe toxicity grades (EUR 9383/week for Grade 1), or even the absence of toxicity (EUR 9922/week), are associated with higher median costs per week (vs. EUR 3266/week for Grade 4 and EUR 2850/week for Grade 3). The cost of toxicities was unexpectedly low compared to the total costs, especially medication costs. Patients with higher toxicity grades had better outcomes and lower total costs due to treatment discontinuation.
Quality of Life in Cutaneous T-cell Lymphoma Patients Receiving Mogamulizumab: Important Factors to Consider
Authors: Ottevanger Rosanne , van Beugen Sylvia , Evers Andrea W. M. , Willemze Rein , Vermeer Maarten H. , Quint Koen D.
Published: December 2022

Background: Erythrodermic cutaneous T-cell lymphoma (E-CTCL) is associated with a poor prognosis and severe symptoms. Objective: To establish insights into the quality of life (QoL), expectations, and treatment satisfaction of E-CTCL patients receiving mogamulizumab. Methods: Outcomes of this prospective cohort study conducted between September 2020 and August 2021 at the Leiden University Medical Center included the dermatology-specific QoL (Skindex-29), health-related QoL (RAND-12), degree of itch, pain, and fatigue (Visual Analogue Scale), patient’s expectations, and treatment satisfaction (Client Satisfaction Questionnaire-8 (CSQ-8)), measured at baseline and after six months. Results: 13 patients with E-CTCL were included. Most patients anticipated a positive treatment effect on symptoms. Five patients (46%) improved one or more clinical categories regarding the symptoms domain, six (55%) regarding emotions, four (36%) regarding functioning, and four (36%) regarding the overall Skindex-29 score compared to baseline. The Mental Component Score clinically improved from 31 (IQR 29–51) at baseline to 38 (IQR 25–51). The median VAS itch improved significantly from baseline (8 (IQR 7–10) vs. 3 (IQR 1–8), p = 0.024). Most patients (n = 7) were “very satisfied” with their treatment. Limitations: There was a limited number of patients due to the rarity of the disease. Conclusion: In general, mogamulizumab has a favorable effect on biochemical- and dermatology-specific QoL and physical functioning in some patients, with high treatment satisfaction. Itch especially improved over time in most patients. The treatment satisfaction was generally high. Mogamulizumab seems to be an effective treatment that improves the QoL in patients with E-CTCL.
A Dosiomics Analysis Based on Linear Energy Transfer and Biological Dose Maps to Predict Local Recurrence in Sacral Chordomas after Carbon-Ion Radiotherapy
Authors: Morelli Letizia , Parrella Giovanni , Molinelli Silvia , Magro Giuseppe , Annunziata Simone , Mairani Andrea , Chalaszczyk Agnieszka , Fiore Maria Rosaria , Ciocca Mario , Paganelli Chiara , Orlandi Ester , Baroni Guido
Published: December 2022

Carbon Ion Radiotherapy (CIRT) is one of the most promising therapeutic options to reduce Local Recurrence (LR) in Sacral Chordomas (SC). The aim of this work is to compare the performances of survival models fed with dosiomics features and conventional DVH metrics extracted from relative biological effectiveness (RBE)-weighted dose (DRBE) and dose-averaged Linear Energy Transfer (LETd) maps, towards the identification of possible prognostic factors for LR in SC patients treated with CIRT. This retrospective study included 50 patients affected by SC with a focus on patients that presented a relapse in a high-dose region. Survival models were built to predict both LR and High-Dose Local Recurrencies (HD-LR). The models were evaluated through Harrell Concordance Index (C-index) and patients were stratified into high/low-risk groups. Local Recurrence-free Kaplan–Meier curves were estimated and evaluated through log-rank tests. The model with highest performance (median(interquartile-range) C-index of 0.86 (0.22)) was built on features extracted from LETd maps, with DRBE models showing promising but weaker results (C-index of 0.83 (0.21), 0.80 (0.21)). Although the study should be extended to a wider patient population, LETd maps show potential as a prognostic factor for SC HD-LR in CIRT, and dosiomics appears to be the most promising approach against more conventional methods (e.g., DVH-based).
Homogeneous and Heterogeneous Catalytic Ozonation of Textile Wastewater: Application and Mechanism
Authors: Bilińska Magdalena , Bilińska Lucyna , Gmurek Marta
Published: December 2022

This paper presents an overview of textile wastewater treatment by catalytic ozonation, highlighting the parameters of the process and accompanying mechanisms. Since more than 800,000 tons of dyes are produced annually and thousands of cubic meters of highly polluted textile wastewater have been emitted into the environment every day, this issue has become an environmental concern. Due to the high oxidative potential of ozone (2.08 V) and hydroxyl radical (2.80 V), the main reactive species in catalytic ozonation, the burdensome organic pollutants, including textile dyes, can be successfully decomposed. The paper shows the main groups of catalysts, emphasizing novel structural, nano-structured, and functionalized materials. The examples of catalytic ozonation in the industrial application for real textile wastewater were specially highlighted.
The Structure, Function and Regulation of Protein Tyrosine Phosphatase Receptor Type J and Its Role in Diseases
Authors: Li Huiting , Zhang Peng , Liu Cencen , Wang Yiwei , Deng Yan , Dong Wei , Yu Yang
Published: December 2022

Protein tyrosine phosphatase receptor type J (PTPRJ), also known as DEP-1, HPTPη, or CD148, belongs to the R3 subfamily of receptor protein tyrosine phosphatases (RPTPs). It was first identified as an antioncogene due to its protein level being significantly downregulated in most epithelial tumors and cancer cell lines (e.g., colon, lung, thyroid, breast, and pancreas). PTPRJ regulates mouse optic nerve projection by inhibiting the phosphorylation of the erythropoietin-producing hepatocellular carcinoma (Eph) receptor and abelson murine leukemia viral oncogene homolog 1 (c-Abl). PTPRJ is crucial for metabolism. Recent studies have demonstrated that PTPRJ dephosphorylates JAK2 at positions Y813 and Y868 to inhibit leptin signaling. Akt is more phosphorylated at the Ser473 and Thr308 sites in Ptprj−/− mice, suggesting that PTPRJ may be a novel negative regulator of insulin signaling. PTPRJ also plays an important role in balancing the pro- and anti-osteoclastogenic activity of the M-CSF receptor (M-CSFR), and in maintaining NFATc1 expression during the late stages of osteoclastogenesis to promote bone-resorbing osteoclast (OCL) maturation. Furthermore, multiple receptor tyrosine kinases (RTKs) as substrates of PTPRJ are probably a potential therapeutic target for many types of diseases, such as cancer, neurodegenerative diseases, and metabolic diseases, by inhibiting their phosphorylation activity. In light of the important roles that PTPRJ plays in many diseases, this review summarizes the structural features of the protein, its expression pattern, and the physiological and pathological functions of PTPRJ, to provide new ideas for treating PTPRJ as a potential therapeutic target for related metabolic diseases and cancer.
Imaging and Manipulation of Plasma Membrane Fatty Acid Clusters Using TOF-SIMS Combined Optogenetics
Authors: Zhang Chi , Kikushima Kenji , Endo Mizuki , Kahyo Tomoaki , Horikawa Makoto , Matsudaira Takaomi , Tanaka Tatsuya , Takanashi Yusuke , Sato Tomohito , Takahashi Yutaka , Xu Lili , Takayama Naoki , Islam Ariful , Mamun Md. Al , Ozawa Takeaki , Setou Mitsutoshi
Published: December 2022

The plasma membrane (PM) serves multiple functions to support cell activities with its heterogeneous molecular distribution. Fatty acids (FAs) are hydrophobic components of the PM whose saturation and length determine the membrane’s physical properties. The FA distribution contributes to the PM’s lateral heterogeneity. However, the distribution of PM FAs is poorly understood. Here, we proposed the FA cluster hypothesis, which suggested that FAs on the PM exist as clusters. By the optogenetic tool translocating the endoplasmic reticulum (ER), we were able to manipulate the distribution of PM FAs. We used time-of-flight combined secondary ion mass spectrometry (TOF-SIMS) to image PM FAs and discovered that PM FAs were presented and distributed as clusters and are also manipulated as clusters. We also found the existence of multi-FA clusters formed by the colocalization of more than one FA. Our optogenetic tool also decreased the clustering degree of FA clusters and the formation probability of multi-FA clusters. This research opens up new avenues and perspectives to study PM heterogeneity from an FA perspective. This research also suggests a possible treatment for diseases caused by PM lipid aggregation and furnished a convenient tool for therapeutic development.