bluuebunny/crossref_metadata_2025 huggingface dataset:
Recommender System Based on Collaborative Filtering for Personalized Dietary Advice: A Cross-Sectional Analysis of the ELSA-Brasil Study
Authors: Silva Vanderlei Carneiro , Gorgulho Bartira , Marchioni Dirce Maria , Alvim Sheila Maria , Giatti Luana , de Araujo Tânia Aparecida , Alonso Angelica Castilho , Santos Itamar de Souza , Lotufo Paulo Andrade , Benseñor Isabela Martins
Published: November 2022

This study aimed to predict dietary recommendations and compare the performance of algorithms based on collaborative filtering for making predictions of personalized dietary recommendations. We analyzed the baseline cross-sectional data (2008–2010) of 12,667 participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). The participants were public employees of teaching and research institutions, aged 35–74 years, and 59% female. A semiquantitative Food Frequency Questionnaire (FFQ) was used for dietary assessment. The predictions of dietary recommendations were based on two machine learning (ML) algorithms—user-based collaborative filtering (UBCF) and item-based collaborative filtering (IBCF). The ML algorithms had similar precision (88–91%). The error metrics were lower for UBCF than for IBCF: with a root mean square error (RMSE) of 1.49 vs. 1.67 and a mean square error (MSE) of 2.21 vs. 2.78. Although all food groups were used as input in the system, the items eligible as recommendations included whole cereals, tubers and roots, beans and other legumes, oilseeds, fruits, vegetables, white meats and fish, and low-fat dairy products and milk. The algorithms’ performances were similar in making predictions for dietary recommendations. The models presented can provide support for health professionals in interventions that promote healthier habits and improve adherence to this personalized dietary advice.
What Is Next for Public Health after COVID-19 in Italy? Adopting a Youth-Centred Care Approach in Mental Health Services
Authors: Ussai Silvia , Castelpietra Giulio , Mariani Ilaria , Casale Andrea , Missoni Eduardo , Pistis Marco , Monasta Lorenzo , Armocida Benedetta
Published: November 2022

Although endeavours to protect mental well-being during the COVID-19 pandemic were taken at national and regional levels, e.g., mental support in school, a COVID-19 emergency toll-free number for psychological support, these were sporadic conjunctural financing interventions. In this Communication, the authors conducted a systematic search for programmatic and policy documents and reports with a solid literature and policy analysis concerning the main objective, which is to analyse the appropriateness in implementing gender- and age-sensitive, integrated, youth-centred mental health services in Italy. The Italian National Action Plan for Mental Health reports a highly fragmented situation in the Child and Adolescent Neuropsychiatry services, in terms of an integrated and comprehensive regional network of services for the diagnosis, treatment, and rehabilitation of neuropsychological disorders in young people. Wide-ranging interventions, systemic actions should be implemented, funded, and included in an overall structural strengthening of the healthcare system, including those dedicated to transition support services. In this context, the National Recovery and Resilience Plan (NRRP), may represent an opportunity to leverage specific funds for mental health in general, and for youth in particular. Finally, mental health service governance should be harmonized at both national and regional EU levels—with the adoption of best practices implemented by other Member States. This includes, among others, health information system and data collection, which is critical for analysing epidemiological trends and for monitoring and evaluating services, to offer a public and integrated system for the care and protection of young people, in line with the Convention on the Rights of the Child.
“Because This Is an Evidence-Based Program”: The Learning Experience of Croatia with the Lions Quest Skills for Adolescence, Implemented In-Person and Online
Authors: El-Khatib Ziad , Brandic Alma Rovis , Yassine Ali , Glavendekic Zana , Maalouf Wadih
Published: November 2022

Background: The Lions Quest Skills for Adolescence (LQSFA) is an evidence-based social and emotional learning program for school students. It is implemented as a teacher-led extracurricular activity for children aged 10–15 years. From 2019 to 2022, the United Nations Office on Drugs and Crime, in collaboration with Lions Clubs International Foundation, implemented the LQSFA in 41 schools in Croatia. Due to the COVID-19 lockdown measures, the intervention was adjusted into a hybrid modality (in-class and online). We evaluated the experience that the teachers had with the LQSFA in a hybrid modality. Methods: We used a focus-group discussion approach to evaluate the experience of five LQSFA teachers. Results: Three themes emerged: (1) the appreciation of evidence-based programs by the teachers, (2) the benefit of the LQSFA on the parents, and (3) the length of the online version of the questionnaire tool that was used to assess pre- and post-LQSFA experiences among students was too long. These results indicate that the LQSFA is undergoing a scaling on a national level in Croatia, even when implemented in a hybrid setting. Conclusions: Using an evidence-based program such as the LQSFA was rewarding for teachers, despite the challenges in the administrative adjustments regarding the online and in-person class teaching. LQSFA filled an important gap during COVID19-related stress.
Mask-Wearing Behaviors after Two Years of Wearing Masks Due to COVID-19 in Korea: A Cross-Sectional Study
Authors: Kwon Miji , Yang Wonyoung
Published: November 2022

In Korea, wearing masks in public places has become the norm during the prolonged coronavirus disease 2019 (COVID-19) pandemic. This cross-sectional study investigated the mask-wearing behavior of Koreans (n = 433) via online mode living in Seoul and Gwangju after wearing a mask in public spaces for two years due to COVID-19. The respondents selected their face masks based on season, gender, age, occupation, mask-wearing hours, mask filter performance, mask shape, and mask color. The general discomfort caused by wearing a mask was divided into physical and speech discomfort, and it was not correlated with anxiety when not wearing a face mask. Speech discomfort caused by wearing a mask was correlated with general discomfort, clear speech, vocal pain, anxiety, and only-indoor mask-off plans. Anxiety when not wearing a mask appeared to affect both indoor and outdoor mask-off plans. The more uncomfortable and less anxious respondents were when not wearing a mask, the sooner they wanted to discontinue wearing masks indoors and outdoors. It is expected that the use of masks will continue in the future and that there may be differences in the place and time of use of masks in Korea and around the world due to new infectious diseases and fine dust. Facial masks can be worn more comfortably and conveniently if the discomfort and anxiety of wearing a mask are improved by considering various behaviors when wearing a mask in the future.
Analysis on the Spatio-Temporal Evolution Characteristics of the Impact of China’s Digitalization Process on Green Total Factor Productivity
Authors: Zhao Junwei , Zhang Yuxiang , Chen Anhang , Zhang Huiqin
Published: November 2022

Green production is an inevitable choice for China’s high-quality economic development. With the rise of the digital technology revolution, China’s digital transformation may play an integral and important role in increasing green total factor productivity (GTFP). Based on the panel data of 30 Chinese provinces from 2014–2020, the impact of digitization on GTFP was explored using the model of geographically and temporally weighted regression (GTWR), and the spatial and temporal distribution characteristics and development trends of such effects were further explored. The main findings are as follows: (1) China’s digitalization level and GTFP has significant spatial autocorrelation and similar spatial distribution characteristics. (2) Digitalization has a significant positive impact on GTFP, but this impact decreases yearly, and there are noticeable regional differences. Digitalization in the eastern and central regions has a more significant impact on GTFP than in the west. (3) The region where China’s digital development has extensively promoted GTFP has shifted from China’s southern coastal region to the northwest and northeast regions. (4) The time-series fluctuations of the regression coefficients of the digitization level in each province in China also show agglomeration characteristics. That is, the regression coefficients of neighboring provinces have similar time-series fluctuations.
Impact of Vitiligo on Life Quality of Patients: Assessment of Currently Available Tools
Authors: Yang Ting-Ting , Lee Chien-Hung , Lan Cheng-Che E.
Published: November 2022

Background: How different tools for evaluating health-related quality of life (QoL) reflect the burden of vitiligo has rarely been compared. In this study, we aim to evaluate the impact of vitiligo on QoL using currently available tools. Methods: A single-center, cross-sectional study of vitiligo patients was performed. QoL was evaluated using the dermatology life quality index (DLQI), short form-36 (SF-36), and willingness to pay (WTP). As the original DLQI cutoff score (>10) indicating aginificantly impated QoL was found to underestimate QoL, receiver operating characteristic (ROC) curve was use to determine a new cutoff point discriminating vitiligo patients with positive mental stress (SF-36 mental health ≤ 52). Results: Of the 143 patients enrolled, 24.5% were identified having significant mental stress by SF-36 mental health domain score ≤ 52 while there were only 13.3% patients with significantly hampered QoL indicated by DLQI >10. Using ROC analysis, DLQI ≥ 7 was found to be a more appropriate DLQI cutoff value for identifying mental stress in vitiligo patients. Additionally, the median WTP for treating vitiligo was comparable to other inflammatory skin diseases. Conclusions: There exist discrepancies in the outcomes identifying significant disease burden of vitiligo using DLQI and SF-36, making the current DLQI cutoff score (>10) for identifying significantly affected QoL inappropriate for these patients.
Performing Arts in Suicide Prevention Strategies: A Scoping Review
Authors: Davico Chiara , Rossi Ghiglione Alessandra , Lonardelli Elena , Di Franco Francesca , Ricci Federica , Marcotulli Daniele , Graziano Federica , Begotti Tatiana , Amianto Federico , Calandri Emanuela , Tirocchi Simona , Carlotti Edoardo Giovanni , Lenzi Massimo , Vitiello Benedetto , Mazza Marianna , Caroppo Emanuele
Published: November 2022

Suicide is a leading cause of death all over the world. Suicide prevention is possible and should be pursued through a variety of strategies. The importance of the arts for positive health outcomes has been increasingly evidenced. This scoping review aimed to identify the possible role of the performing arts—defined as a type of art performed through actions such as music, dance, or drama executed alive by an artist or other participant in the presence of an audience,—in suicide prevention programs. PubMed, Embase, PsycINFO, CINAHL, ProQuest Psychology Database, Scopus, and Web of Science were searched using terms in English for publications of original studies that included performing arts in suicide prevention programs. Thirty-five studies conducted between 1981 and 2021 were identified, of which only five were randomized clinical trials and four quasi-randomized studies. Interventions used different performing arts to improve awareness, self-efficacy, and soft skills relevant to suicide prevention. Studies were addressed mainly to gatekeepers but also directly to at-risk populations. While the study designs do not allow inferences to be drawn about the effectiveness of performing arts in preventing suicide, the review found that performing arts have been successfully implemented in suicide prevention programs. Research to evaluate the possible therapeutic benefit is warranted.
Self-Medication in Rural Northeastern Romania: Patients’ Attitudes and Habits
Authors: Rusu Razvan-Nicolae , Ababei Daniela-Carmen , Bild Walther , Stoian Ioana , Macadan Ioana , Stanciu Gabriela Dumitrita , Ciobica Andrei , Bild Veronica
Published: November 2022

In recent years, many healthcare systems, along with healthcare professionals, have provided services in a patient-centered manner, in which patients are key actors in the care process. Encouraging self-care creates responsible patients, but it must be practiced responsibly. This study aims to analyze the tendency towards self-medication for patients from a rural area in Northeastern Romania. Data were collected using a questionnaire, which consisted of 25 questions, that has been developed by the research team. Student’s T test or one-way ANOVA was used, and the reliability of the questionnaire was calculated using Cronbach’s alpha coefficient. Fifty-eight patients agreed to participate and were interviewed. The results of the study suggest that respondents practice self-medication, which they resort to when their condition cannot be treated with natural remedies or herbs and when it impairs their ability to do their daily activities. Self-medication could be explained by the lack of self-care services as well as the trust patients have in the specific treatment. Patients prefer asking the pharmacist for drugs instead of visiting a physician, which could be due to higher accessibility and time-efficiency, while also being prone to stock up on certain medications due to limited access to healthcare.
A Research on Accident Reconstruction of Bus–Two-Wheeled Vehicle Based on Vehicle Damage and Human Head Injury
Authors: Gao Shang , Li Mao , Wang Qian , Jin Xianlong , Hou Xinyi , Qin Chuang , Fu Shuangzhi
Published: November 2022

The problem of large calculation models in bus–two-wheeled vehicle traffic accidents (TA) leads to the difficulty of balancing the calculation efficiency and accuracy, as well as difficulties in accident reconstruction. Herein, two typical accidents were reconstructed, based on the rigid–flexible coupled human model (HM) and the Facet vehicle model, and the vehicle damage conditions and the human head biomechanical injury were analyzed. The simulation results showed that the physical process of the human–vehicle collision was basically consistent with the accident video, the windshield fracture was consistent with the actual vehicle report, and the human biomechanical injury characteristics were also consistent with the autopsy report, which verified the feasibility of the simulation model, and provides a basis and reference for forensic identification and for traffic police to deal with accident disputes.
Proposal of a New Rating Concept for Digital Health Applications in Orthopedics and Traumatology
Authors: Scherer Julian , Youssef Yasmin , Dittrich Florian , Albrecht Urs-Vito , Tsitsilonis Serafeim , Jung Jochen , Pförringer Dominik , Landgraeber Stefan , Beck Sascha , Back David A.
Published: November 2022

Background: Health-related mobile applications (apps) are rapidly increasing in number. There is an urgent need for assessment tools and algorithms that allow the usability and content criteria of these applications to be objectively assessed. The aim of this work was to establish and validate a concept for orthopedic societies to rate health apps to set a quality standard for their safe use. Methods: An objective rating concept was created, consisting of nine quality criteria. A self-declaration sheet for app manufacturers was designed. Manufacturers completed the self-declaration, and the app was examined by independent internal reviewers. The pilot validation and analysis were performed on two independent health applications. An algorithm for orthopedic societies was created based on the experiences in this study flow. Results: “Sprunggelenks-App“ was approved by the reviewers with 45 (98%) fulfilled criteria and one (2%) unfulfilled criterion. “Therapie-App” was approved, with 28 (61%) met criteria, 6 (13%) unfulfilled criteria and 12 (26%) criteria that could not be assessed. The self-declaration completed by the app manufacturer is recommended, followed by a legal and technical rating performed by an external institution. When rated positive, the societies’ internal review using independent raters can be performed. In case of a positive rating, a visual certification can be granted to the manufacturer for a certain time frame. Conclusion: An objective rating algorithm is proposed for the assessment of digital health applications. This can help societies to improve the quality assessment, quality assurance and patient safety of those apps. The proposed concept must be further validated for inter-rater consistency and reliability.
Pandemic Meets Endemic: The Role of Social Inequalities and Failing Public Health Policies as Drivers of Disparities in COVID-19 Mortality among White, Black, and Hispanic Communities in the United States of America
Authors: Frisina Doetter Lorraine , Frisina Pasquale G. , Preuß Benedikt
Published: November 2022

The COVID-19 pandemic placed the United States of America (U.S.) under enormous strain, leaving it with higher deaths during the first wave of the outbreak compared to all other advanced economies. Blacks and Hispanics were among those hardest hit by the virus—a fact attributed to enduring problems related to the social determinants of health adversely affecting Communities of Color (CoC). In this study, we ask which distinct factors relating to policy stringency and community vulnerability influenced COVID-19 mortality among Whites, Blacks, and Hispanics during the first year of the pandemic. To address this question, we utilized a mix of correlational and regression analyses. Findings point to the highly divergent impact of public policy and vulnerability on COVID-19 mortality. Specifically, we observed that state-led measures aimed at controlling the spread of the virus only improved mortality for Whites. However, pre-existing social determinants of health (i.e., population density, epidemiological and healthcare system factors) played a significant role in determining COVID-19 outcomes for CoC, even in the face of stringent containment measures by states. This suggests that state-led policy to address present and/or future public health crises need to account for the particular nature of vulnerability affecting Blacks and Hispanics in the U.S.
Individual Differences in the Association of Lifestyle with Cardiometabolic Risk in Middle-Aged Koreans Based on Traditional Korean Medicine
Authors: Baek Younghwa , Park Kihyun , Jung Kyoungsik , Lee Siwoo
Published: November 2022

Cardiometabolic (CM) risk differs in morbidity and disease progression depending on lifestyle and individual characteristics. This cross-sectional study aimed to analyze the association between CM risk and lifestyle and examine whether this association varies based on Sasang constitution (SC), a Korean medicine classification. Data were analyzed from 1996 individuals participating in the Korean Medicine Daejeon Citizen Cohort study. Individuals with CM risk had two to five CM risk factors. Lifestyle factors included physical activity, sleep duration, and eating index. SC types were Taeeum-in (TE) and non-TE. We estimated the odds ratio (OR) and 95% confidence interval for CM risk based on SC and lifestyle factors. Among the participants, 33.9% had a CM risk, and the TE and non-TE groups were 26.2% and 7.7%, respectively. In the TE group, CM risk was associated with low physical activity (OR, 1.63) and moderate eating index (OR, 1.41). In the non-TE group, CM risk was associated with ≥8 h of sleep (OR, 1.87) and marginally associated with ≤6 h of sleep. In the TE group alone, CM risk was significantly associated with lifestyle patterns that combined the three lifestyle factors and was approximately two-fold higher in patterns involving less physical activity. The effects of lifestyle on CM risk differed across SC types. To decrease the burden of cardiovascular diseases in middle-aged adults, we recommend an individualized management strategy of healthy lifestyle interventions for cardiovascular risks.
Reliability and Validity of the Motor Activity Log (MAL-30) Scale for Post-Stroke Patients in a Spanish Sample
Authors: Santamaría-Peláez Mirian , Pardo-Hernández Rocío , González-Bernal Jerónimo J. , Soto-Cámara Raúl , González-Santos Josefa , Fernández-Solana Jessica
Published: November 2022

Background: The validation of assessment instruments is of great importance when they are applied in clinical and healthcare settings, since their safe and reliable use is essential for the application of appropriate and high-quality treatments. The motor activity log (MAL-30) is an instrument widely used by professionals in the clinic, which has been validated in different countries, languages and populations. The aim of this study was to determine the reliability and validity of the MAL-30 scale for post-stroke patients in a Spanish sample. Methods: For this purpose, internal consistency tests were carried out using Cronbach’s alpha, item–item and item–total correlations, and a half-and-half test for reliability. For the validation, criterion validity tests were performed using the Fugl-Meyer assessment scale as the gold standard, and the convergent validity tests were carried out by correlation with the action research arm test (ARAT), box and block test (BBT), functional independence measure (FIM)–functional assessment measure (FAM), Lawton and Brody index and stroke quality of life scale (ECVI-38). Results: The results showed good internal consistency, as well as a good criterion and convergent validity. Conclusions: The MAL-30 instrument can be considered a valid and reliable tool for assessing the quantity and quality of the use of the affected upper limb in the performance of the activities of daily living and the instrumental activities of daily living after stroke in a Spanish sample.
Presenteeism in Non-Academic Staff in a Public University Context: Prevalence, Associated Factors, and Reasons to Work While Sick during the COVID-19 Pandemic
Authors: Magalhães Sónia , Barbosa Joselina , Borges Elisabete
Published: November 2022

Presenteeism negatively affects worker performance. We aimed to know the prevalence of presenteeism in non-academic university staff, identify health problems and associated factors, as well as explore the reasons that led to presenteeism during the COVID-19 pandemic. A cross-sectional study was conducted with a convenience sample of 332 non-academic staff. The Portuguese version of the Stanford Presenteeism Scale (SPS-6) was used, and socio-demographic and occupational data were collected. Participants were divided into groups according to the presenteeism cut-off score (no presenteeists, presenteeists with high job performance, presenteeists with low job performance). Multinomial regression was used to identify occupational and demographic characteristics associated with presenteeism. An open question replies analysis made it possible to explore the reasons for going to work while sick. Presenteeism was experienced by 30.1%. Presenteeism with high job performance was not associated with socio-demographic and work factors. Professionals who performed only physical work (OR = 9.4; 95% CI: 1.7; 51.0) and those who conducted hybrid work (OR = 4.1; 95% CI: 1.8; 9.6) showed a higher risk of belonging to the presenteeist group with low job performance. Financial reasons led professionals to work while sick. This study raises the importance of evaluating presenteeism in non-academic staff to create conditions for them to maintain high performance despite presenteeism and to intervene when there is low performance due to presenteeism.
Mothers’ Awareness of the Correlation between Their Own and Their Children’s Oral Health
Authors: Ludovichetti Francesco Saverio , Zuccon Andrea , Lucchi Patrizia , Cattaruzza Giulia , Zerman Nicoletta , Stellini Edoardo , Mazzoleni Sergio
Published: November 2022

Pregnancy is a critical time for a woman since it involves a series of changes in the body due to hormonal fluctuations and changes that can also influence the oral cavity and can lead to certain pathologies, such as carious lesions. Furthermore, it has been demonstrated over the years that having poor dental health during pregnancy might have a significant impact on the child’s oral health. The aim of the study is to analyze the level of knowledge and information of mothers on the importance of oral health care before, during, and after pregnancy as a preventive factor for the future oral health of the child. A questionnaire of 13 multiple choice questions was formulated and delivered from 24 February 2022 to 13 July 2022, aimed at women with at least one child. The Department of Pediatric Dentistry of the Borgo Cavalli Clinic in Treviso and the Maxillofacial Surgery Department of Santa Maria di Ca’ Foncello Hospital in Treviso were the data collection centers. Crosstabs with dependency variables were used to statistically analyze the results. The study cohort consists of 411 women, whose responses showed that the majority did not have dental visits before and during pregnancy, which is why 74% of the whole sample did not request or receive information from professionals. Most mothers knew that they had to cleanse their child’s mouth and, among them, those who responded more correctly, that is, who started before the eruption of the teeth, had received instructions from professionals. However, the low frequency of mothers performing dental checks during pregnancy did not allow mothers to become aware of the possibility of transmitting the carious lesions to their child, as conscious mothers represent 21%. Education from dentist and dental hygienists, gynecologists, and pediatricians is essential since they have an impact on mothers’ habits and behaviors and ensure favorable oral health for both the mother and the child.
Optimization of Complex Function Expansions for Gauss-Krüger Projections
Authors: Li Xiaoyong , Li Houpu , Liu Guohui , Bian Shaofeng
Published: November 2022

Compared with complex and lengthy Gauss-Krüger projection series expansions and real number expressions, we improve the complex function representation of Gauss-Krüger projections and rewrite them into the “multiple Angle form”, “exponential form”, and “double Angle form”. The coefficients were expanded in the power series based on the first eccentricity e and the third flattening n, respectively, and the truncation difference was analyzed when expanded to different orders to obtain the simplified practical formulas for each form on the premise of meeting the accuracy requirements of geodesy. Through numerical analysis, the computational efficiency of the forward and inverse solutions of the Gauss-Krüger projection is analyzed, which shows the superiority of the “double Angle form”. Through the above measures, the expressions for forward and inverse solutions of the Gauss-Krüger projection are obtained, meeting the accuracy requirements with a higher computational efficiency and a more concise form.
The Verification of Land Cover Datasets with the Geo-Tagged Natural Scene Images
Authors: Cui Liu , Yang Hui , Chu Liang , He Qingping , Xu Fei , Qiao Yina , Yan Zhaojin , Wang Ran , Ci Hui
Published: November 2022

Land cover is important for global change studies, and its accuracy and reliability are usually verified by field sampling, which costs a lot. A method was proposed for the verification of land cover datasets with the geo-tagged natural scene images using a convolutional neural network. The nature scene images were firstly collected from the Land Use and Cover Area frame Survey (LUCAS) and global crowdsourcing images platform Flickr, then classified according to the Land Cover Classification System. The Nature Scene Image Classification (NSIC) model based on the GoogLeNet Inception network for recognition of natural scene images was then constructed. Finally, in the UK, as a verification area, the European Space Agency Climate Change Initiative Land Cover (ESA CCI-LC) datasets and the Global land-cover product with fine classification system (GLC-FCS) were verified using the NSIC-Inception model with the nature scene image set. The verification results showed that the overall accuracy verified by LUCAS was very close to the accuracy of the land cover product, which was 94.41% of CCI LC and 92.89% of GLC-FCS, demonstrating the feasibility of using geo-tagged images classified by the NSIC model. In addition, the VGG16 and ResNet50 were compared with GoogLeNet Inception. The differences in verification between LUCAS and Flickr images were discussed regarding the image’s quantity, the spatial distribution, the representativeness, and so on. The uncertainties of verification arising from differences in the spatial resolution of the different datasets were explored by CCI LC and GCL-FCS. The application of the method has great potential to support and improve the efficiency of land cover verification.
Insights into Antiviral Properties and Molecular Mechanisms of Non-Flavonoid Polyphenols against Human Herpesviruses
Authors: Hassan Sherif T. S. , Šudomová Miroslava , Mazurakova Alena , Kubatka Peter
Published: November 2022

Herpesviruses are one of the most contagious DNA viruses that threaten human health, causing severe diseases, including, but not limited to, certain types of cancer and neurological complications. The overuse and misuse of anti-herpesvirus drugs are key factors leading to drug resistance. Therefore, targeting human herpesviruses with natural products is an attractive form of therapy, as it might improve treatment efficacy in therapy-resistant herpesviruses. Plant polyphenols are major players in the health arena as they possess diverse bioactivities. Hence, in this article, we comprehensively summarize the recent advances that have been attained in employing plant non-flavonoid polyphenols, such as phenolic acids, tannins and their derivatives, stilbenes and their derivatives, lignans, neolignans, xanthones, anthraquinones and their derivatives, curcuminoids, coumarins, furanocoumarins, and other polyphenols (phloroglucinol) as promising anti-herpesvirus drugs against various types of herpesvirus such as alpha-herpesviruses (herpes simplex virus type 1 and 2 and varicella-zoster virus), beta-herpesviruses (human cytomegalovirus), and gamma-herpesviruses (Epstein–Barr virus and Kaposi sarcoma-associated herpesvirus). The molecular mechanisms of non-flavonoid polyphenols against the reviewed herpesviruses are also documented.
The Crosstalk between FcεRI and Sphingosine Signaling in Allergic Inflammation
Authors: Jo Hyein , Shim Kyeonghee , Jeoung Dooil
Published: November 2022

Sphingolipid molecules have recently attracted attention as signaling molecules in allergic inflammation diseases. Sphingosine-1-phosphate (S1P) is synthesized by two isoforms of sphingosine kinases (SPHK 1 and SPHK2) and is known to be involved in various cellular processes. S1P levels reportedly increase in allergic inflammatory diseases, such as asthma and anaphylaxis. FcεRI signaling is necessary for allergic inflammation as it can activate the SPHKs and increase the S1P level; once S1P is secreted, it can bind to the S1P receptors (S1PRs). The role of S1P signaling in various allergic diseases is discussed. Increased levels of S1P are positively associated with asthma and anaphylaxis. S1P can either induce or suppress allergic skin diseases in a context-dependent manner. The crosstalk between FcεRI and S1P/SPHK/S1PRs is discussed. The roles of the microRNAs that regulate the expression of the components of S1P signaling in allergic inflammatory diseases are also discussed. Various reports suggest the role of S1P in FcεRI-mediated mast cell (MC) activation. Thus, S1P/SPHK/S1PRs signaling can be the target for developing anti-allergy drugs.
High pH Alleviated Sweet Orange (Citrus sinensis) Copper Toxicity by Enhancing the Capacity to Maintain a Balance between Formation and Removal of Reactive Oxygen Species and Methylglyoxal in Leaves and Roots
Authors: Zhang Jiang , Chen Xu-Feng , Huang Wei-Lin , Chen Huan-Huan , Huang Zeng-Rong , Ye Xin , Chen Li-Song
Published: November 2022

The contribution of reactive oxygen species (ROS) and methylglyoxal (MG) formation and removal in high-pH-mediated alleviation of plant copper (Cu)-toxicity remains to be elucidated. Seedlings of sweet orange (Citrus sinensis) were treated with 0.5 (non-Cu-toxicity) or 300 (Cu-toxicity) μM CuCl2 × pH 4.8, 4.0, or 3.0 for 17 weeks. Thereafter, superoxide anion production rate; H2O2 production rate; the concentrations of MG, malondialdehyde (MDA), and antioxidant metabolites (reduced glutathione, ascorbate, phytochelatins, metallothioneins, total non-protein thiols); and the activities of enzymes (antioxidant enzymes, glyoxalases, and sulfur metabolism-related enzymes) in leaves and roots were determined. High pH mitigated oxidative damage in Cu-toxic leaves and roots, thereby conferring sweet orange Cu tolerance. The alleviation of oxidative damage involved enhanced ability to maintain the balance between ROS and MG formation and removal through the downregulation of ROS and MG formation and the coordinated actions of ROS and MG detoxification systems. Low pH (pH 3.0) impaired the balance between ROS and MG formation and removal, thereby causing oxidative damage in Cu-toxic leaves and roots but not in non-Cu-toxic ones. Cu toxicity and low pH had obvious synergistic impacts on ROS and MG generation and removal in leaves and roots. Additionally, 21 (4) parameters in leaves were positively (negatively) related to the corresponding root parameters, implying that there were some similarities and differences in the responses of ROS and MG metabolisms to Cu–pH interactions between leaves and roots.
MET Signaling Pathways, Resistance Mechanisms, and Opportunities for Target Therapies
Authors: Rivas Solange , Marín Arnaldo , Samtani Suraj , González-Feliú Evelin , Armisén Ricardo
Published: November 2022

The MET gene, known as MET proto-oncogene receptor tyrosine kinase, was first identified to induce tumor cell migration, invasion, and proliferation/survival through canonical RAS-CDC42-PAK-Rho kinase, RAS-MAPK, PI3K-AKT-mTOR, and β-catenin signaling pathways, and its driver mutations, such as MET gene amplification (METamp) and the exon 14 skipping alterations (METex14), activate cell transformation, cancer progression, and worse patient prognosis, principally in lung cancer through the overactivation of their own oncogenic and MET parallel signaling pathways. Because of this, MET driver alterations have become of interest in lung adenocarcinomas since the FDA approval of target therapies for METamp and METex14 in 2020. However, after using MET target therapies, tumor cells develop adaptative changes, favoring tumor resistance to drugs, the main current challenge to precision medicine. Here, we review a link between the resistance mechanism and MET signaling pathways, which is not only limited to MET. The resistance impacts MET parallel tyrosine kinase receptors and signals shared hubs. Therefore, this information could be relevant in the patient’s mutational profile evaluation before the first target therapy prescription and follow-up to reduce the risk of drug resistance. However, to develop a resistance mechanism to a MET inhibitor, patients must have access to the drugs. For instance, none of the FDA approved MET inhibitors are registered as such in Chile and other developing countries. Constant cross-feeding between basic and clinical research will thus be required to meet future challenges imposed by the acquired resistance to targeted therapies.
Vanadium in Bipolar Disorders—Reviving an Old Hypothesis
Authors: Sampath Vishnu Priya , Singh Shiv Vardan , Pelov Ilana , Horesh Noa , Zannadeh Hiba , Tirosh Ofir , Erel Yigal , Lichtstein David
Published: November 2022

Bipolar disorder (BD) is a severe and common chronic mental illness. The biological basis of the disease is poorly understood and its treatment is unsatisfactory. Our previous studies supported the notion that alterations in Na+, K+-ATPase activity were involved in the etiology of BD. As various chemical elements inhibit Na+, K+-ATPase, we determined the concentration of 26 elements in the serum of BD patients before and after treatment and in postmortem brain samples from BD patients, and compared them with matched controls. The only element that was reduced significantly in the serum following treatment was vanadium (V). Furthermore, the concentration of V was significantly lower in the pre-frontal cortex of BD patients compared with that of the controls. Intracerebroventricular administration of V in mice elicited anxiolytic and depressive activities, concomitantly inhibited brain Na+, K+-ATPase activity, and increased extracellular signal-regulated kinase phosphorylation. A hypothesis associating V with BD was set forth decades ago but eventually faded out. Our results are in accord with the hypothesis and advocate for a thorough examination of the possible involvement of chemical elements, V in particular, in BD.
Oncometabolism: A Paradigm for the Metabolic Remodeling of the Failing Heart
Authors: Kuhn Annika-Ricarda , van Bilsen Marc
Published: November 2022

Heart failure is associated with profound alterations in cardiac intermediary metabolism. One of the prevailing hypotheses is that metabolic remodeling leads to a mismatch between cardiac energy (ATP) production and demand, thereby impairing cardiac function. However, even after decades of research, the relevance of metabolic remodeling in the pathogenesis of heart failure has remained elusive. Here we propose that cardiac metabolic remodeling should be looked upon from more perspectives than the mere production of ATP needed for cardiac contraction and relaxation. Recently, advances in cancer research have revealed that the metabolic rewiring of cancer cells, often coined as oncometabolism, directly impacts cellular phenotype and function. Accordingly, it is well feasible that the rewiring of cardiac cellular metabolism during the development of heart failure serves similar functions. In this review, we reflect on the influence of principal metabolic pathways on cellular phenotype as originally described in cancer cells and discuss their potential relevance for cardiac pathogenesis. We discuss current knowledge of metabolism-driven phenotypical alterations in the different cell types of the heart and evaluate their impact on cardiac pathogenesis and therapy.
Whole Transcriptome Analysis of Breast Cancer Tumors during Neoadjuvant Chemotherapy: Association with Hematogenous Metastasis
Authors: Ibragimova Marina K. , Tsyganov Matvey M. , Litviakov Nikolai V.
Published: November 2022

The assessment of molecular genetic landscape changes during NAC and the relationship between molecular signatures in residual tumors are promising approaches for identifying effective markers of outcome in breast cancer. The majority of the data in the literature present the relationship between the molecular genetic landscape and the response to NAC or are simply descriptive. The present study aimed to determine changes in expression profiles during NAC and assess the relationship between gene expression and the outcome of patients with luminal B HER2 breast cancer depending on distant hematogenous metastasis. The study included 39 patients with luminal B HER2-BC. The patients received 6–8 courses of NAC, and paired samples consisting of biopsy and surgical materials were analyzed. A full transcriptome microarray analysis was performed using the human Clariom™ S Assay platform (Affymetrix, 3450 Central Expy, Santa Clara, CA, 95051, USA). A comparison of the expression profiles of patients with breast cancer before and after NAC, depending on the status of hematogenous metastasis, was conducted. It was shown that the amount of DEGs in the tumor was reduced by more than six times after NAC. The top 10 signaling pathways were also found, the activity of which varied depending on the status of hematogenous metastasis before and after NAC. In addition, the association of DEGs with hematogenous metastasis in patients with breast cancer was evaluated: MFS was assessed depending on the expression level of 21 genes. It was shown that MFS was significantly associated with the expression level and pattern of nine genes. The expression levels of nine DEGs in the tumors of patients with breast cancer after NAC were significantly correlated with MFS when the status of hematogenous metastasis was taken into account.
Efficacy and Safety of Angiotensin Receptor Blockers in a Pre-Clinical Model of Arrhythmogenic Cardiomyopathy
Authors: Landim-Vieira Maicon , Kahmini Aida Rahimi , Engel Morgan , Cannon Elisa Nicole , Amat-Alarcon Nuria , Judge Daniel P. , Pinto José Renato , Chelko Stephen P.
Published: November 2022

Arrhythmogenic Cardiomyopathy (ACM) is a familial heart disease, characterized by contractile dysfunction, ventricular arrhythmias (VAs), and the risk of sudden cardiac death. Currently, implantable cardioverter defibrillators and antiarrhythmics are the mainstays in ACM therapeutics. Angiotensin receptor blockers (ARBs) have been highlighted in the treatment of heart diseases, including ACM. Yet, recent research has additionally implicated ARBs in the genesis of VAs and myocardial lipolysis via the peroxisome proliferator-activated receptor gamma (PPARγ) pathway. The latter is of particular interest, as fibrofatty infiltration is a pathological hallmark in ACM. Here, we tested two ARBs, Valsartan and Telmisartan, and the PPAR agonist, Rosiglitazone, in an animal model of ACM, homozygous Desmoglein-2 mutant mice (Dsg2mut/mut). Cardiac function, premature ventricular contractions (PVCs), fibrofatty scars, PPARα/γ protein levels, and PPAR-mediated mRNA transcripts were assessed. Of note, not a single mouse treated with Rosiglitazone made it to the study endpoint (i.e., 100% mortality: n = 5/5). Telmisartan-treated Dsg2mut/mut mice displayed the preservation of contractile function (percent ejection fraction [%EF]; 74.8 ± 6.8%EF) compared to Vehicle- (42.5 ± 5.6%EF) and Valsartan-treated (63.1 ± 4.4%EF) mice. However, Telmisartan-treated Dsg2mut/mut mice showed increased cardiac wall motion abnormalities, augmented %PVCs, electrocardiographic repolarization/depolarization abnormalities, larger fibrotic lesions, and increased expression of PPARy-regulated gene transcripts compared to their Dsg2mut/mut counterparts. Alternatively, Valsartan-treated Dsg2mut/mut mice harbored fewer myocardial scars, reduced %PVC, and increased Wnt-mediated transcripts. Considering our findings, caution should be taken by physicians when prescribing medications that may increase PPARy signaling in patients with ACM.
Engineering Modified mRNA-Based Vaccine against Dengue Virus Using Computational and Reverse Vaccinology Approaches
Authors: Mukhtar Mamuna , Wajeeha Amtul Wadood , Zaidi Najam us Sahar Sadaf , Bibi Naseeha
Published: November 2022

Dengue virus belonging to the family Flaviviridae and its four serotypes are responsible for dengue infections, which extend over 60 countries in tropical and subtropical areas of the world including Pakistan. During the ongoing dengue outbreak in Pakistan (2022), over 30,000 cases have been reported, and over 70 lives have been lost. The only commercialized vaccine against DENV, Dengvaxia, cannot be administered as a prophylactic measure to cure this infection due to various complications. Using machine learning and reverse vaccinology approaches, this study was designed to develop a tetravalent modified nucleotide mRNA vaccine using NS1, prM, and EIII sequences of dengue virus from Pakistani isolates. Based on high antigenicity, non-allergenicity, and toxicity profiling, B-cell epitope, cytotoxic T lymphocyte (CTL), and helper T lymphocyte (HTL) putative vaccine targets were predicted. Molecular docking confirmed favorable interactions between T-cell epitopes and their respective HLA alleles, while normal mode analysis validated high-affinity interactions of vaccine proteins with immune receptors. In silico immune simulations confirmed adequate immune responses to eliminate the antigen and generate memory. Codon optimization, physicochemical features, nucleotide modifications, and suitable vector availability further ensured better antigen expression and adaptive immune responses. We predict that this vaccine construct may prove to be a good vaccinal candidate against dengue virus in vitro as well.
A New Hybrid Neural Network Deep Learning Method for Protein–Ligand Binding Affinity Prediction and De Novo Drug Design
Authors: Limbu Sarita , Dakshanamurthy Sivanesan
Published: November 2022

Accurately predicting ligand binding affinity in a virtual screening campaign is still challenging. Here, we developed hybrid neural network (HNN) machine deep learning methods, HNN-denovo and HNN-affinity, by combining the 3D-CNN (convolutional neural network) and the FFNN (fast forward neural network) hybrid neural network framework. The HNN-denovo uses protein pocket structure and protein–ligand interactions as input features. The HNN-affinity uses protein sequences and ligand features as input features. The HNN method combines the CNN and FCNN machine architecture for the protein structure or protein sequence and ligand descriptors. To train the model, the HNN methods used thousands of known protein–ligand binding affinity data retrieved from the PDBBind database. We also developed the Random Forest (RF), Gradient Boosting (GB), Decision Tree with AdaBoost (DT), and a consensus model. We compared the HNN results with models developed based on the RF, GB, and DT methods. We also independently compared the HNN method results with the literature reported deep learning protein–ligand binding affinity predictions made by the DLSCORE, KDEEP, and DeepAtom. The predictive performance of the HNN methods (max Pearson’s R achieved was 0.86) was consistently better than or comparable to the DLSCORE, KDEEP, and DeepAtom deep learning learning methods for both balanced and unbalanced data sets. The HNN-affinity can be applied for the protein–ligand affinity prediction even in the absence of protein structure information, as it considers the protein sequence as standalone feature in addition to the ligand descriptors. The HNN-denovo method can be efficiently implemented to the structure-based de novo drug design campaign. The HNN-affinity method can be used in conjunction with the deep learning molecular docking protocols as a standalone. Further, it can be combined with the conventional molecular docking methods as a multistep approach to rapidly screen billions of diverse compounds. The HNN method are highly scalable in the cloud ML platform.
Therapeutic Utility and Adverse Effects of Biologic Disease-Modifying Anti-Rheumatic Drugs in Inflammatory Arthritis
Authors: Min Hong Ki , Kim Se Hee , Kim Hae-Rim , Lee Sang-Heon
Published: November 2022

Targeting specific pathologic pro-inflammatory cytokines or related molecules leads to excellent therapeutic effects in inflammatory arthritis, including rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. Most of these agents, known as biologic disease-modifying anti-rheumatic drugs (bDMARDs), are produced in live cell lines and are usually monoclonal antibodies. Several types of monoclonal antibodies target different pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-17A, IL-6, and IL-23/12. Some bDMARDs, such as rituximab and abatacept, target specific cell-surface molecules to control the inflammatory response. The therapeutic effects of these bDMARDs differ in different forms of inflammatory arthritis and are associated with different adverse events. In this article, we summarize the therapeutic utility and adverse effects of bDMARDs and suggest future research directions for developing bDMARDs.