bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishing a novel model of malignant airway stenosis in rabbit
Authors: Lin Xiaoxiao , Zhou Liqin , Zhou Wanting , Li Yuping , Jin Xuru , Ye Min , Chen Chengshui
Published: August 2022

Background

Malignant central airway stenosis is a life-threatening condition. However, treatment of malignant airway stenosis remains challenging. There is currently a severe lack of an excellent animal model of malignant airway stenosis to facilitate treatment approaches. This is the first study to establish a rabbit model of malignant airway stenosis for bronchoscopic interventional studies.

Materials and methods

New Zealand White rabbits were used in this study, randomly divided into group A (18 rabbits) and group B (6 rabbits). A VX2 fragment suspension was injected into the submucosal layer of rabbits’ airway by bronchoscopy. Bronchoscopic examinations were performed once a week after VX2 tumor implantation to observe tumor growth and the degree of airway stenosis. Randomly, three rabbits were generally dissected after a weekly bronchoscopic examination in group A. The rabbits that reached grade III airway stenosis underwent stent implantation in group B.

Results

A total of 24 rabbits were successfully implanted with the VX2 fragment suspension in the airway without significant adverse events, and the success rate of the tumor growth was 100%. The degree of airway stenosis reaching grade III took 2 to 3 weeks after implantation of the VX2 tumor. The median survival time of rabbit models without stent implantation and rabbits with stent implantation was 32.5 and 32.0 days, respectively.

Conclusions

The implanting method is safe and effective for the establishment of a rabbit model of malignant airway stenosis. When the tumor grows to 2 to 3 weeks, the rabbit model is available for stent implantation. We recommend the models for more preclinical animal studies on bronchoscopic interventional treatments.
Congenital midline spinal hamartoma in an infant with DICER1 syndrome: A case report
Authors: Hammad Rawan , Lo Winnie , Chen Haiying , Shroff Manohar , Malkin David , Villani Anita , Denburg Avram
Published: August 2022

Congenital spinal hamartomas are rare benign tumors. They are mostly seen in infants and are typically asymptomatic at presentation. Spinal hamartomas have not been associated with any known cancer predisposition syndrome. DICER1 syndrome is a well-characterized cancer predisposition syndrome caused by a germline mutation in the DICER1 gene, which shows variable expressivity. To our knowledge, spinal hamartoma has never been described in individuals with DICER1 syndrome. Here, we describe a rare association of congenital spinal hamartoma and DICER1 syndrome in a 5-week-old infant, with molecular findings suggestive of the implication of DICER1 in the pathogenesis of this tumor.
Three categories of similarities between the placenta and cancer that can aid cancer treatment: Cells, the microenvironment, and metabolites
Authors: Pang Huiyuan , Lei Di , Guo Yuping , Yu Ying , Liu Tingting , Liu Yujie , Chen Tingting , Fan Cuifang
Published: August 2022

Cancer is one of the most harmful diseases, while pregnancy is a common condition of females. Placenta is the most important organ for fetal growth, which has not been fully understand. It’s well known that placenta and solid tumor have some similar biological behaviors. What’s more, decidua, the microenvironment of placenta, and metabolism all undergo adaptive shift for healthy pregnancy. Interestingly, decidua and the tumor microenvironment (TME); metabolism changes during pregnancy and cancer cachexia all have underlying links. However, whether the close link between pregnancy and cancer can bring some new ideas to treat cancer is still unclear. So, in this review we note that pregnancy may offer clues to treat cancer related to three categories: from cell perspective, through the shared development process of the placenta and cancer; from microenvironment perspective, though the shared features of the decidua and TME; and from metabolism perspective, through shared metabolites changes during pregnancy and cancer cachexia. Firstly, comparing gene mutations of both placenta and cancer, which is the underlying mechanism of many similar biological behaviors, helps us understand the origin of cancer and find the key factors to restore tumorigenesis. Secondly, exploring how decidua affect placenta development and similarities of decidua and TME is helpful to reshape TME, then to inhibit cancer. Thirdly, we also illustrate the possibility that the altered metabolites during pregnancy may reverse cancer cachexia. So, some key molecules changed in circulation of pregnancy may help relieve cachexia and make survival with cancer realized.
Aberrant DNA methylation in multiple myeloma: A major obstacle or an opportunity?
Authors: Muylaert Catharina , Van Hemelrijck Lien Ann , Maes Anke , De Veirman Kim , Menu Eline , Vanderkerken Karin , De Bruyne Elke
Published: August 2022

Drug resistance (DR) of cancer cells leading to relapse is a huge problem nowadays to achieve long-lasting cures for cancer patients. This also holds true for the incurable hematological malignancy multiple myeloma (MM), which is characterized by the accumulation of malignant plasma cells in the bone marrow (BM). Although new treatment approaches combining immunomodulatory drugs, corticosteroids, proteasome inhibitors, alkylating agents, and monoclonal antibodies have significantly improved median life expectancy, MM remains incurable due to the development of DR, with the underlying mechanisms remaining largely ill-defined. It is well-known that MM is a heterogeneous disease, encompassing both genetic and epigenetic aberrations. In normal circumstances, epigenetic modifications, including DNA methylation and posttranslational histone modifications, play an important role in proper chromatin structure and transcriptional regulation. However, in MM, numerous epigenetic defects or so-called ‘epimutations’ have been observed and this especially at the level of DNA methylation. These include genome-wide DNA hypomethylation, locus specific hypermethylation and somatic mutations, copy number variations and/or deregulated expression patterns in DNA methylation modifiers and regulators. The aberrant DNA methylation patterns lead to reduced gene expression of tumor suppressor genes, genomic instability, DR, disease progression, and high-risk disease. In addition, the frequency of somatic mutations in the DNA methylation modifiers seems increased in relapsed patients, again suggesting a role in DR and relapse. In this review, we discuss the recent advances in understanding the involvement of aberrant DNA methylation patterns and/or DNA methylation modifiers in MM development, progression, and relapse. In addition, we discuss their involvement in MM cell plasticity, driving myeloma cells to a cancer stem cell state characterized by a more immature and drug-resistant phenotype. Finally, we briefly touch upon the potential of DNA methyltransferase inhibitors to prevent relapse after treatment with the current standard of care agents and/or new, promising (immuno) therapies.
Genotypes and clinical intervention of patients with neurofibromatosis type 1 associated dystrophic scoliosis
Authors: Li Haichong , Zhang Wenyan , Yao Ziming , Guo Ruolan , Hao Chanjuan , Zhang Xuejun
Published: August 2022

Objective

To analyze the genotypic characteristics of patients with neurofibromatosis type 1 (NF1) associated dystrophic scoliosis and to summarize the outcomes of the surgical treatment of these patients.

Methods

Exome sequencing (ES) combined with multiplex ligation-dependent probe amplification (MLPA) was used for genotypic identification. All patients underwent surgical treatments for spinal deformities, and the outcomes of the surgery was summarized by analyzing the clinical and imaging parameters before and after the surgery.

Results

Fourteen patients (six males and eight females) were clinically diagnosed as NF1 associated dystrophic scoliosis with common symptoms including café-au-lait spots, paravertebral tumors, and dystrophic scoliosis. NF1 mutations were detected in 12 (85.7%) patients, including four nonsense mutations, three splicing mutations, three frameshift mutations, and two exon deletions. The first surgical procedure included growing-rod surgery in 10 patients and posterior spinal fusion in four patients. The follow-up duration was 2.3 years (1.0–10.3 years), and the Cobb angle of the main curve improved from 61.5° (30°-125°) pre-operatively to 14.5° (0°-42°) at the last follow-up, with an average correction rate of 74.0% (44–100%). Instrumentation-related complications occurred in four patients during the follow-up period.

Conclusions

In patients with dystrophic scoliosis who met the clinical diagnostic criteria for NF1, the mutation detection rate of ES combined with MLPA was 85.7%. There was no mutation hotspot in NF1 gene, molecular diagnosis could offer information about genetic counseling, prenatal diagnosis and eugenics. Surgical treatment according to patient's age and severity could effectively correct the spinal deformities.
Transient proteolysis reduction of Nicotiana benthamiana-produced CAP256 broadly neutralizing antibodies using CRISPR/Cas9
Authors: Singh Advaita Acarya , Pillay Priyen , Naicker Previn , Alexandre Kabamba , Malatji Kanyane , Mach Lukas , Steinkellner Herta , Vorster Juan , Chikwamba Rachel , Tsekoa Tsepo L.
Published: August 2022

The hypersensitive response is elicited by Agrobacterium infiltration of Nicotiana benthamiana, including the induction and accumulation of pathogenesis-related proteins, such as proteases. This includes the induction of the expression of several cysteine proteases from the C1 (papain-like cysteine protease) and C13 (legumain-like cysteine protease) families. This study demonstrates the role of cysteine proteases: NbVPE-1a, NbVPE-1b, and NbCysP6 in the proteolytic degradation of Nicotiana benthamiana (glycosylation mutant ΔXTFT)-produced anti-human immunodeficiency virus broadly neutralizing antibody, CAP256-VRC26.25. Three putative cysteine protease cleavage sites were identified in the fragment crystallizable region. We further demonstrate the transient coexpression of CAP256-VRC26.25 with CRISPR/Cas9-mediated genome editing vectors targeting the NbVPE-1a, NbVPE-1b, and NbCysP6 genes which resulted in a decrease in CAP256-VRC26.25 degradation. No differences in structural features were observed between the human embryonic kidney 293 (HEK293)-produced and ΔXTFT broadly neutralizing antibodies produced with and without the coexpression of genome-editing vectors. Furthermore, despite the presence of proteolytically degraded fragments of plant-produced CAP256-VRC26.25 without the coexpression of genome editing vectors, no influence on the in vitro functional activity was detected. Collectively, we demonstrate an innovative in planta strategy for improving the quality of the CAP256 antibodies through the transient expression of the CRISPR/Cas9 vectors.
Simply effective? The differential effects of solution-focused and problem-focused coaching questions in a self-coaching writing exercise
Authors: Solms Lara , Koen Jessie , van Vianen Annelies E. M. , Theeboom Tim , Beersma Bianca , de Pagter Anne P. J. , de Hoog Matthijs
Published: August 2022

Coaching is a systematic and goal-oriented one-on-one intervention by a coach aimed to guide clients in their professional and personal development. Previous research on coaching has demonstrated effects on a number of positive outcomes, including well-being and performance, yet little is known about the processes that underlie these outcomes, such as the type of questions coaches use. Here, we focus on three different types of coaching questions, and aim to uncover their immediate and sustained effects for affect, self-efficacy, and goal-directed outcomes, using a between-subjects experiment. One hundred and eighty-three medical residents and PhD students from various medical centers and healthcare organizations in the Netherlands were recruited to participate in a self-coaching writing exercise, where they followed written instructions rather than interacting with a real coach. All participants were randomly allocated to one of three conditions: either one of two solution-focused coaching conditions (i.e., the success or miracle condition) or a problem-focused coaching condition. Self-report questionnaires were used to measure key outcomes of coaching, that is positive and negative affect, self-efficacy, goal orientation, action planning (i.e., quantity and quality) and goal attainment. Two follow-up measurements assessed if the effects of the self-coaching exercise led to problem-solving actions within an initial follow-up period of 14 days and a subsequent follow-up period of 10 days. Findings showed that participants experienced more positive affect, less negative affect, and higher approach goal orientation after the solution-focused coaching exercise compared to the problem-focused coaching exercise. In all conditions, goal attainment increased as a consequence of the self-coaching intervention. We discuss the implications of our findings for the science and practice of contemporary coaching.
Relationship between parental psychological control and suicide ideation in Chinese adolescents: Chained mediation through resilience and maladjustment problems
Authors: Sun Ji , Ban Yongfei
Published: August 2022

Suicide ideation is an essential predictor of suicide deaths and is highly prevalent among Chinese adolescents. Several studies have highlighted the significant association between parental psychological control and suicide ideation. However, few studies have focused on the potential mechanisms underlying this relationship. This study investigated the chained mediating effects of resilience and maladjustment problems on the relationship between parental psychological control and suicide ideation among Chinese adolescents. A total of 2,042 students in junior high school completed measurements. The results revealed significant correlations among parental psychological control, resilience, maladjustment problems and suicide ideation. Even after controlling for the effects of gender and grade, parental psychological control positively predicted a significant effect of suicide ideation. Furthermore, suicide ideation was linked with parental psychological control through three pathways: the mediating role of resilience, the mediating role of maladjustment problems, and the chained mediating roles of resilience and maladjustment problems. These findings have broad implications for the field of suicide studies. High levels of parental psychological control, low levels of resilience, and high levels of maladjustment problems may increase the occurrence of suicide ideation.
RETRACTED: An empirical analysis of the impact of higher education on economic growth: The case of China
Authors: Qi Di , Ali Arshad , Li Tao , Chen Yuan-Chun , Tan Jiachao
Published: August 2022

China's domestic labor market has limited demand for tertiary graduates due to an unbalanced industrial structure, with a weak contribution to economic performance over the past decade. This study estimates the asymmetric effects of higher education progress (highly educated employed workforce), higher education utilization (highly educated unemployed workforce), and the separate effects of higher education utilization interactions with high-tech industries on economic growth in China from 1980 to 2020. Using a Nonlinear Autoregressive Distributed Lag (NARDL) model, this study finds that the expansion of higher education progress (the employed workforce with higher education) promotes economic growth, while contraction of higher education progress (employed workforce with higher education) reduces economic growth. Likewise, an increase in higher education utilization (the unemployed labor force with higher education) suppresses economic growth, while a decline in the higher education utilization (the unemployed labor force with higher education) promotes economic growth. The study also found that the expansion of high-tech industries and government spending on education significantly stimulate economic growth. The moderating role of higher education utilization (unemployed labor force with higher education) in the impact of high-tech industries on economic growth is significantly positive. This study strategically proposes that China's higher-educated unemployed labor force can be adjusted to high-tech industries, which need to be developed equally in all regions. Moreover, the country is required to invest more in higher education and the development of high technological industries across all regions, thus may lead to higher economic growth.
Enhancing neuroimaging genetics through meta-analysis for Tourette syndrome (ENIGMA-TS): A worldwide platform for collaboration
Authors: Paschou Peristera , Jin Yin , Müller-Vahl Kirsten , Möller Harald E. , Rizzo Renata , Hoekstra Pieter J. , Roessner Veit , Mol Debes Nanette , Worbe Yulia , Hartmann Andreas , Mir Pablo , Cath Danielle , Neuner Irene , Eichele Heike , Zhang Chencheng , Lewandowska Katarzyna , Munchau Alexander , Verrel Julius , Musil Richard , Silk Tim J. , Hanlon Colleen A. , Bihun Emily D. , Brandt Valerie , Dietrich Andrea , Forde Natalie , Ganos Christos , Greene Deanna J. , Chu Chunguang , Grothe Michel J. , Hershey Tamara , Janik Piotr , Koller Jonathan M. , Martin-Rodriguez Juan Francisco , Müller Karsten , Palmucci Stefano , Prato Adriana , Ramkiran Shukti , Saia Federica , Szejko Natalia , Torrecuso Renzo , Tumer Zeynep , Uhlmann Anne , Veselinovic Tanja , Wolańczyk Tomasz , Zouki Jade-Jocelyne , Jain Pritesh , Topaloudi Apostolia , Kaka Mary , Yang Zhiyu , Drineas Petros , Thomopoulos Sophia I. , White Tonya , Veltman Dick J. , Schmaal Lianne , Stein Dan J. , Buitelaar Jan , Franke Barbara , van den Heuvel Odile , Jahanshad Neda , Thompson Paul M. , Black Kevin J.
Published: August 2022

Tourette syndrome (TS) is characterized by multiple motor and vocal tics, and high-comorbidity rates with other neuropsychiatric disorders. Obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), autism spectrum disorders (ASDs), major depressive disorder (MDD), and anxiety disorders (AXDs) are among the most prevalent TS comorbidities. To date, studies on TS brain structure and function have been limited in size with efforts mostly fragmented. This leads to low-statistical power, discordant results due to differences in approaches, and hinders the ability to stratify patients according to clinical parameters and investigate comorbidity patterns. Here, we present the scientific premise, perspectives, and key goals that have motivated the establishment of the Enhancing Neuroimaging Genetics through Meta-Analysis for TS (ENIGMA-TS) working group. The ENIGMA-TS working group is an international collaborative effort bringing together a large network of investigators who aim to understand brain structure and function in TS and dissect the underlying neurobiology that leads to observed comorbidity patterns and clinical heterogeneity. Previously collected TS neuroimaging data will be analyzed jointly and integrated with TS genomic data, as well as equivalently large and already existing studies of highly comorbid OCD, ADHD, ASD, MDD, and AXD. Our work highlights the power of collaborative efforts and transdiagnostic approaches, and points to the existence of different TS subtypes. ENIGMA-TS will offer large-scale, high-powered studies that will lead to important insights toward understanding brain structure and function and genetic effects in TS and related disorders, and the identification of biomarkers that could help inform improved clinical practice.
Evaluation of whole-genome sequence to predict drug resistance of nine anti-tuberculosis drugs and characterize resistance genes in clinical rifampicin-resistant Mycobacterium tuberculosis isolates from Ningbo, China
Authors: Che Yang , Lin Yi , Yang Tianchi , Chen Tong , Sang Guoxin , Chen Qin , He Tianfeng
Published: August 2022

Setting

Controlling drug-resistant tuberculosis in Ningbo, China.

Objective

Whole-genome sequencing (WGS) has not been employed to comprehensively study Mycobacterium tuberculosis isolates, especially rifampicin-resistant tuberculosis, in Ningbo, China. Here, we aim to characterize genes involved in drug resistance in RR-TB and create a prognostic tool for successfully predicting drug resistance in patients with TB.

Design

Drug resistance was predicted by WGS in a “TB-Profiler” web service after phenotypic drug susceptibility tests (DSTs) against nine anti-TB drugs among 59 clinical isolates. A comparison of consistency, sensitivity, specificity, and positive and negative predictive values between WGS and DST were carried out for each drug.

Results

The sensitivities and specificities for WGS were 95.92 and 90% for isoniazid (INH), 100 and 64.1% for ethambutol (EMB), 97.37 and 100% for streptomycin (SM), 75 and 100% for amikacin (AM), 80 and 96.3%for capreomycin (CAP), 100 and 97.22% for levofloxacin (LFX), 93.33 and 90.91% for prothionamide (PTO), and 70 and 97.96% for para-aminosalicylic acid (PAS). Around 53 (89.83%) and 6 (10.17%) of the isolates belonged to lineage two (East-Asian) and lineage four (Euro-American), respectively.

Conclusion

Whole-genome sequencing is a reliable method for predicting resistance to INH, RIF, EMB, SM, AM, CAP, LFX, PTO, and PAS with high consistency, sensitivity, and specificity. There was no transmission that occurred among the patients with RR-TB in Ningbo, China.
Precision medicine for risk prediction of oral complications of cancer therapy–The example of oral mucositis in patients receiving radiation therapy for cancers of the head and neck
Authors: Sonis Stephen T.
Published: August 2022

Oral complications of cancer therapy are common, markedly symptomatic, negatively impact patients' quality of life, and add significantly to the cost of care. Patients' risk of treatment-related toxicities is not uniform; most patients suffer at least one side effect, while others tolerate treatment without any. Understanding those factors which impact risk provides opportunities to customize cancer treatment plans to optimize tumor kill and minimize regimen-related toxicities. Oral mucositis (OM) is an iconic example of a clinically significant and common complication of head and neck radiotherapy. Individuals' OM risk is governed by the cumulative impact of factors related to treatment, the tumor, and the patient. In addition to OM risk prediction, a second opportunity to apply precision medicine will evolve as viable treatment options become available. Patients vary widely in how well or poorly they respond to specific treatments. What works well in one individual, might fail in another. Prospective determination of the likelihood of a patient's response or non-response is based on a range of biological interactions. Coupled with risk determination, the application of precision medicine will allow caregivers, patients, and payers to integrate risk/benefit to optimize the probability that the best treatment is be given to the most appropriate patients.
Social Media Hate Speech Detection Using Explainable Artificial Intelligence (XAI)
Authors: Mehta Harshkumar , Passi Kalpdrum
Published: August 2022

Explainable artificial intelligence (XAI) characteristics have flexible and multifaceted potential in hate speech detection by deep learning models. Interpreting and explaining decisions made by complex artificial intelligence (AI) models to understand the decision-making process of these model were the aims of this research. As a part of this research study, two datasets were taken to demonstrate hate speech detection using XAI. Data preprocessing was performed to clean data of any inconsistencies, clean the text of the tweets, tokenize and lemmatize the text, etc. Categorical variables were also simplified in order to generate a clean dataset for training purposes. Exploratory data analysis was performed on the datasets to uncover various patterns and insights. Various pre-existing models were applied to the Google Jigsaw dataset such as decision trees, k-nearest neighbors, multinomial naïve Bayes, random forest, logistic regression, and long short-term memory (LSTM), among which LSTM achieved an accuracy of 97.6%. Explainable methods such as LIME (local interpretable model—agnostic explanations) were applied to the HateXplain dataset. Variants of BERT (bidirectional encoder representations from transformers) model such as BERT + ANN (artificial neural network) with an accuracy of 93.55% and BERT + MLP (multilayer perceptron) with an accuracy of 93.67% were created to achieve a good performance in terms of explainability using the ERASER (evaluating rationales and simple English reasoning) benchmark.
Experimental Study into Optimal Configuration and Operation of Two-Four Rotor Coaxial Systems for eVTOL Vehicles
Authors: Prasad Rao Jubilee , Holzsager Jonathan E. , Maia Marco M. , Diez Javier F.
Published: August 2022

Coaxial rotors are utilized in multirotor aerial vehicles for the added thrust compared to independent rotors while keeping similar area footprints; however, performance losses should be considered. This experimental study analyzes the effects of varying motor duty cycle and propeller pitch values in motor-propeller systems with two to four coaxial rotors. The results demonstrate that in a two-rotor coaxial system, to lessen the adverse effects of a front rotor’s backwash and operate at the maximum performance, only the back motor should be operated initially up to 75% duty cycle before using the front motor up to its 75% duty cycle. Additional thrust requirements should be generated from the back rotor and then from the front rotor up to their maximum duty cycles. In two, three, and four-rotor coaxial setups, total thrust output generated is 1.6, 2.1, and 2.5 times the thrust output at system thrust performance of 86%, 76%, and 66%, respectively, of that of an isolated rotor. In a four-rotor coaxial setup, the maximum system performance is achieved when the propeller pitch values gradually increase from the first to the last rotor. The gradual increments in propeller pitch values also result in more uniform thrust sharing among rotors.
Cold Atmospheric Plasma Targeting Hematological Malignancies: Potentials and Problems of Clinical Translation
Authors: Gangemi Sebastiano , Petrarca Claudia , Tonacci Alessandro , Di Gioacchino Mario , Musolino Caterina , Allegra Alessandro
Published: August 2022

Cold atmospheric plasma is an ionized gas produced near room temperature; it generates reactive oxygen species and nitrogen species and induces physical changes, including ultraviolet, radiation, thermal, and electromagnetic effects. Several studies showed that cold atmospheric plasma could effectively provoke death in a huge amount of cell types, including neoplastic cells, via the induction of apoptosis, necrosis, and autophagy. This technique seems able to destroy tumor cells by disturbing their more susceptible redox equilibrium with respect to normal cells, but it is also able to cause immunogenic cell death by enhancing the immune response, to decrease angiogenesis, and to provoke genetic and epigenetics mutations. Solutions activated by cold gas plasma represent a new modality for treatment of less easily reached tumors, or hematological malignancies. Our review reports on accepted knowledge of cold atmospheric plasma’s effect on hematological malignancies, such as acute and chronic myeloid leukemia and multiple myeloma. Although relevant progress was made toward understanding the underlying mechanisms concerning the efficacy of cold atmospheric plasma in hematological tumors, there is a need to determine both guidelines and safety limits that guarantee an absence of long-term side effects.
The Histone Deacetylase Inhibitor ITF2357 (Givinostat) Targets Oncogenic BRAF in Melanoma Cells and Promotes a Switch from Pro-Survival Autophagy to Apoptosis
Authors: Celesia Adriana , Notaro Antonietta , Franzò Marzia , Lauricella Marianna , D’Anneo Antonella , Carlisi Daniela , Giuliano Michela , Emanuele Sonia
Published: August 2022

Histone deacetylase inhibitors (HDACI) are epigenetic compounds that have been widely considered very promising antitumor agents. Here, we focus on the effects of the pan-HDAC inhibitor ITF2357 (Givinostat) in comparison with SAHA (Vorinostat) in melanoma cells bearing BRAF V600E oncogenic mutation. Our results indicate both ITF2357 and SAHA dose-dependently reduce the viability of BRAF-mutated SK-MEL-28 and A375 melanoma cells. The comparison of IC50 values revealed that ITF2357 was much more effective than SAHA. Interestingly, both inhibitors markedly decreased oncogenic BRAF protein expression levels, ITF2357 being the most effective compound. Moreover, the BRAF decrease induced by ITF2357 was accompanied by a decrease in the level of phospho-ERK1/2. The inhibitor of upstream MEK activity, U0126, reduced ERK1/2 phosphorylation and dramatically potentiated the antitumor effect of ITF2357, exacerbating the reduction in the BRAF level. ITF2357 stimulated an early pro-survival autophagic response, which was followed by apoptosis, as indicated by apoptotic markers evaluation and the protective effects exerted by the pan-caspase inhibitor z-VADfmk. Overall, our data indicate for the first time that ITF2357 targets oncogenic BRAF in melanoma cells and induces a switch from autophagy to classic apoptosis, thus representing a possible candidate in melanoma targeted therapy.
WAMD: From Pathophysiology to Therapeutic Treatments
Authors: Menna Feliciana , Meduri Alessandro , Lupo Stefano , Vingolo Enzo Maria
Published: August 2022

Age-related macular degeneration (AMD) is referred to as the leading cause of irreversible visual loss in developed countries, with a profound effect on the quality of life [...]
An Economical and Portable Paper-Based Colorimetric Sensor for the Determination of Hydrogen Peroxide-Related Biomarkers
Authors: Zhang Wei-Yi , Zhang Hao , Yang Feng-Qing
Published: August 2022

In this study, a paper-based sensor was developed for the detection of hydrogen-peroxide-related biomarkers, with glucose oxidase catalyzing as an example. Potassium iodide can catalyze the oxidation of 3,3′,5,5′-tetramethylbenzidine in the presence of hydrogen peroxide to colorize the paper-based biosensor detection area, which was imaged by a scanner, and the color intensity was analyzed by the Adobe Photoshop. Under the optimal conditions, the color intensity shows a good linear relationship with hydrogen peroxide and glucose concentrations in the ranges of 0.1–5.0 mM and 0.5–6.0 mM, respectively. The detection limit of hydrogen peroxide is 0.03 mM and the limit of quantification of glucose is 0.5 mM. Besides, the method was employed in measuring glucose concentration in fruit samples, and the spiked recoveries are in the range of 95.4–106.1%. This method is cost-effective, environmentally friendly, and easy to be operated, which is expected to realize the point-of-care testing of more hydrogen-peroxide-related biomarkers.
Spatio-Temporal Dynamics of Entropy in EEGS during Music Stimulation of Alzheimer’s Disease Patients with Different Degrees of Dementia
Authors: Wu Tingting , Sun Fangfang , Guo Yiwei , Zhai Mingwei , Yu Shanen , Chu Jiantao , Yu Chenhao , Yang Yong
Published: August 2022

Music has become a common adjunctive treatment for Alzheimer’s disease (AD) in recent years. Because Alzheimer’s disease can be classified into different degrees of dementia according to its severity (mild, moderate, severe), this study is to investigate whether there are differences in brain response to music stimulation in AD patients with different degrees of dementia. Seventeen patients with mild-to-moderate dementia, sixteen patients with severe dementia, and sixteen healthy elderly participants were selected as experimental subjects. The nonlinear characteristics of electroencephalogram (EEG) signals were extracted from 64-channel EEG signals acquired before, during, and after music stimulation. The results showed the following. (1) At the temporal level, both at the whole brain area and sub-brain area levels, the EEG responses of the mild-to-moderate patients showed statistical differences from those of the severe patients (p < 0.05). The nonlinear characteristics during music stimulus, including permutation entropy (PmEn), sample entropy (SampEn), and Lempel–Ziv complexity (LZC), were significantly higher in both mild-to-moderate patients and healthy controls compared to pre-stimulation, while it was significantly lower in severe patients. (2) At the spatial level, the EEG responses of the mild-to-moderate patients and the severe patients showed statistical differences (p < 0.05), showing that as the degree of dementia progressed, fewer pairs of EEG characteristic showed significant differences among brain regions under music stimulation. In this paper, we found that AD patients with different degrees of dementia had different EEG responses to music stimulation. Our study provides a possible explanation for this discrepancy in terms of the pathological progression of AD and music cognitive hierarchy theory. Our study has adjunctive implications for clinical music therapy in AD., potentially allowing for more targeted treatment. Meanwhile, the variations in the brains of Alzheimer’s patients in response to music stimulation might be a model for investigating the neural mechanism of music perception.
The Evaluation of Technological Competencies among Leaders of the Renewable Energy Industry: The Case of SMEs in Baja California, Mexico
Authors: Candolfi-Arballo Norma , Hualde-Alfaro Alfredo , Espinosa-Díaz Yessica , Avitia-Carlos Patricia , Rodríguez-Tapia Bernabé
Published: August 2022

This research explores and analyzes the context of the renewable energies industry sector of Baja California, Mexico, regarding the adoption, appropriation, knowledge and usage of Information and Communication Technologies (ICTs) by focusing on human resources, mainly its business managers and directors, as key actors of strategic plans in terms of research and technological development. For this task, a Technological Competencies Profile (TCP), meant for evaluating the incorporation of ICTs by business leaders, was constructed by reviewing the definition of “technological competency” in 140 publications, and by considering the European e-Competence Framework (e-CF), the Skills Framework for the Information Age (SFIA), and other related guidelines. This profile was later applied to analyze 13 SMEs and their leaders’ technological competencies. The investigation was further enriched with the information extracted from 13 interviews made with renewable energy experts in Baja California. The conclusions of this study show that, although SME leaders do have knowledge of ICTs and use them effectively for their own communicative and personal purposes, they do not consider them as a part of their business operation that can optimize their processes and impact its innovative capabilities.
Special Issue “Environmental Technology Applications in the Retrofitting of Residential Buildings”
Authors: Luther Mark B. , Martek Igor , Amirkhani Mehdi , Zucker Gerhard
Published: August 2022

The architectural and construction professions are in a state of major transition [...]
Extremal Dependence Modelling of Global Horizontal Irradiance with Temperature and Humidity: An Application Using South African Data
Authors: Sigauke Caston , Ravele Thakhani , Jhamba Lordwell
Published: August 2022

The interaction between global horizontal irradiance (GHI) and temperature helps determine the maximum amount of solar power generated. As temperature increases, GHI increases up to the point that it increases at a decreasing rate and then decreases. Therefore, system operators need to know the maximum possible solar power which can be generated. Using the multivariate adaptive regression splines, extreme value theory and copula models, the present paper seeks to determine the maximum temperature that will result in the generation of the maximum GHI ceteris paribus. The paper also discusses extremal dependence modelling of GHI with temperature and relative humidity (RH) at one radiometric station using South African data from 16 November 2015 to 16 November 2021. Empirical results show that the marginal increases of GHI converge to 0.12 W/m2 when temperature converges to 44.26 °C and the marginal increases of GHI converge to −0.1 W/m2 when RH converges to 103.26%. Conditioning on GHI, the study found that temperature and RH variables have a negative extremal dependence on large values of GHI. Due to the nonlinearity and different structure of the dependence on GHI against temperature and RH, unlike previous literature, we use three Archimedean copula functions: Clayton, Frank and Gumbel, to model the dependence structure. The modelling approach discussed in this paper could be useful to system operators in power utilities who must optimally integrate highly intermittent renewable energies on the grid.
DC Soft Open Points for Resilient and Reconfigurable DC Distribution Networks
Authors: Ramadan Husam A. , Skarvelis-Kazakos Spyros
Published: August 2022

This paper introduces the concept, theory of operation and applications of soft open points for direct current networks (DCSOPs). The DCSOP is based on a bidirectional DC–DC converter actively controlled to behave like a normal conductor. Unlike the normal conductor, the DCSOP can transfer the electric power between nodes at different voltage levels. With this advantage, the DCSOP can effectively control the power flow direction. Thus, DCSOPs can play a vital role in the reconfiguration of DC distribution networks. The operation and control of the DCSOP device was investigated, both in transient and steady-state conditions. Then, a DCSOP was integrated into a DC microgrid model to validate its ability to change the power flow through the modelled feeders. In addition, a set of reliability indicators was calculated for the DC microgrid under different reconfiguration scenarios. It was shown that reliability is improved when the DCSOP device implements network reconfiguration. Finally, an agent-based framework for controlling the DCSOP in a DC microgrid is presented. A fundamental implementation was created for reconfiguring a DC microgrid with a DCSOP controlled by an agent, proving that the agent-based system can effectively control the DCSOP device for reconfiguration and voltage regulation.
Water Losses in the Condenser Cooling System at the 905 MWe Power Unit
Authors: Pospolita Janusz , Kuczuk Anna , Widera Katarzyna , Buryn Zbigniew , Cholewa Robert , Drajczyk Andrzej , Pietrucha Mirosław , Smejda Rafał
Published: August 2022

The paper focuses on water losses in the turbine condenser cooling system of the 905 MW power unit in Opole Power Plant (Opole Poland). The evaporative and drift losses are determined for various operating and atmospheric conditions. The drift loss is found to be 0.125–0.375% of the cooling water flux and some increase in this loss is noticed with increase in unit power and ambient temperature. The studies have shown that the presence of wind increases the total water loss related to the power generated by the power unit. This effect is analysed for selected constant air temperature values Tamb. The increase of the cooling water loss stream, related to the power of the unit, is at the level of 14.8% for Tamb equal to 7 °C, 23% for 15 °C, and approximately 10% at 22 °C. These increases are related to the level of losses in almost no wind conditions. It is investigated how the change in the cooling water flux affects the power unit operation and the amount of water loss. For the power unit under consideration, the reduction of the cooling water flux from 80,000 to 60,000 ton/h raises the temperature of water behind the condenser and lowers the temperature of the cooled water tw2 within the range of 0.75–1.5 °C, depending on the unit power and the ambient temperature. Reducing the cooling water flux in the analysed range results in an increase in condenser vapour pressure, within 0.5 kPa at Tamb = 25 °C. This increase is lower at lower ambient temperatures. Within the range of variations analysed, the effect of cooling water flux on evaporative losses is negligibly small. The increase in condenser steam pressure significantly affects the power generated by the turbine generator unit. The calculations show that it is possible to optimize the size of the cooling water flux for the analysed power unit and condenser cooling system. This optimization would allow (within a limited range of load variability) an increase in the net power generated by the power unit.
Development of a Tailored Sol-Gel Immobilized Biocatalyst for Sustainable Synthesis of the Food Aroma Ester n-Amyl Caproate in Continuous Solventless System
Authors: Vasilescu Corina , Paul Cristina , Marc Simona , Hulka Iosif , Péter Francisc
Published: August 2022

This study reports the synthesis of a hybrid sol-gel material, based on organically modified silanes (ORMOSILs) with epoxy functional groups, and its application in the stabilization of lipase type B from Candida antarctica (CalB) through sol-gel entrapment. The key immobilization parameters in the sol-gel entrapment of lipase using epoxysilanes were optimized by the design of numerous experiments, demonstrating that glycidoxypropyl-trimethoxysilane can allow the formation of a matrix with excellent properties in view of the biocatalytic esterifications catalyzed by this lipase, at an enzyme loading of 25 g/mol of silane. The characterization of the immobilized biocatalyst and the correlation of its catalytic efficiency with the morphological and physicochemical properties of the sol-gel matrix was accomplished through scanning electron microscopy (SEM), fluorescence microscopy (FM), as well as thermogravimetric and differential thermal analysis (TGA/DTA). The operational and thermal stability of lipase were increased as a result of immobilization, with the entrapped lipase retaining 99% activity after 10 successive reaction cycles in the batch solventless synthesis of n-amyl caproate. A possible correlation of optimal productivity and yield was attempted for this immobilized lipase via the continuous flow synthesis of n-amyl caproate in a solventless system. The robustness and excellent biocatalytic efficiency of the optimized biocatalyst provide a promising solution for the synthesis of food-grade flavor esters, even at larger scales.
Assessing the Impact of Variety, Irrigation, and Plant Distance on Predatory and Phytophagous Insects in Chili
Authors: Juhász András Lajos , Szalai Márk , Szénási Ágnes
Published: August 2022

Chilies are plants that are becoming increasingly popular all over the world, including in Hungary. Since little is known about the abundance and seasonal dynamic of insect pests and their natural enemies associated with chilies under Hungarian climatic conditions, the aim of the study was to monitor these organisms on different varieties under different growing conditions to provide data for improving IPM for chilies. Chili varieties “Yellow Scotch Bonnet” (YSB) and “Trinidad Scorpion Butch T” (TSBT) were planted with three replicates. Two different plant-to-plant distances (30 vs. 40 and 40 vs. 60 cm in YSB, TSBT, respectively) and two different irrigation frequencies (daily, 40 min; every second day, 20 min) were used. Fifty flowers/plot/date were collected. In 2019, Orius (Hemiptera: Anthocoridae) larvae, and in 2021, phytophagous thrips larvae were dominant in all the treatments. Significantly more Orius adults and larvae were found in the YSB than in the TSBT variety and the number of Aeolothrips and phytophagous thrips (Thysanoptera: Thripidae) adults was significantly higher under less irrigation in 2019. The plant spacing did not affect the abundance of predators or herbivores. Upon comparing the two years, no effect of the treatments on the studied insect taxa was observed.
Multimorbidity Clusters in the Oldest Old: Results from the EpiChron Cohort
Authors: Ioakeim-Skoufa Ignatios , Clerencia-Sierra Mercedes , Moreno-Juste Aida , Elías de Molins Peña Carmen , Poblador-Plou Beatriz , Aza-Pascual-Salcedo Mercedes , González-Rubio Francisca , Prados-Torres Alexandra , Gimeno-Miguel Antonio
Published: August 2022

Multimorbidity is challenging for both patients and healthcare systems due to its increasing prevalence and high impact on people’s health and well-being. The risk of multimorbidity increases with age, but there is still more to discover regarding the clinical profile of the oldest old. In this study, we used information from the EpiChron Cohort Study to identify multimorbidity patterns in individuals who died during the period 2010–2019 at the ages of 80–89, 90–99, and ≥100. This cohort links the demographic, clinical, and drug dispensation information of public health system users in Aragón, Spain. We saw a significantly lower number of chronic diseases and drugs and a lower prevalence of polypharmacy in centenarians compared to those aged 80–99. K-means clustering revealed different multimorbidity clusters by sex and age group. We observed clusters of cardiovascular and metabolic diseases, obstructive pulmonary conditions, and neoplasms, amongst other profiles. One in three octogenarian women had a metabolic pattern (diabetes, dyslipidaemia, and other endocrine–metabolic disorders) with the highest number of diseases (up to seven) and prevalence of polypharmacy (64%). We observed clusters of dementia and genitourinary disorders in individuals on medication with anticholinergic activity. Our study offers an opportunity to better understand the urgency of adequately addressing multimorbidity in our older adults.
The Influencing Factors of HIV-Preventive Behavior Based on Health Belief Model among HIV-Negative MSMs in Western China: A Structural Equation Modeling Analysis
Authors: Liu Hui , Lai Guichuan , Shi Guiqian , Zhong Xiaoni
Published: August 2022

(1) Background: Men who have sex with other men (MSMs) are at high risk of being infected by the human immunodeficiency virus (HIV) in western China. Pre-exposure prophylaxis (PrEP) is an efficient way to prevent HIV transmission. However, adherence is the most vital determinant factor affecting PrEP effectiveness. We conducted a study based on the Health Belief Model to explore factors that predict adherence to PrEP among a cohort of 689 MSMs in western China. (2) Methods: We assessed perceived susceptibility, severity, benefits, barriers, self-efficacy, cues to action, and HIV-preventive behavior through a cross-sectional survey. (3) Results: PrEP self-efficacy was directly associated with PrEP behaviors (β = 0.221, p < 0.001), cues to action were directly associated with PrEP behaviors (β = 0.112, p < 0.001), perceived benefits were directly associated with PrEP behaviors (β = 0.101, p < 0.001), and perceived susceptibility was directly associated with PrEP behaviors (β = 0.117, p = 0.043). (4) Conclusion: Medication self-efficacy, perceived susceptibility, and cue to action structures are predictors of the MSMs’ HIV-preventive behavior in western China. These results will provide theoretical plans for promoting PrEP adherence in MSMs.