bluuebunny/crossref_metadata_2025 huggingface dataset:
Technological Developments, Exercise Training Programs, and Clinical Outcomes in Cardiac Telerehabilitation in the Last Ten Years: A Systematic Review
Authors: Garofano Marina , Vecchione Carmine , Calabrese Mariaconsiglia , Rusciano Maria Rosaria , Visco Valeria , Granata Giovanni , Carrizzo Albino , Galasso Gennaro , Bramanti Placido , Corallo Francesco , Izzo Carmine , Ciccarelli Michele , Bramanti Alessia
Published: August 2024

Background: Cardiovascular diseases (CVDs) are associated with very high rates of re-hospitalization and mortality worldwide, so the complexity of these pathologies requires frequent access to hospital facilities. The guidelines also emphasize the importance of cardiac rehabilitation (CR) programs, which have demonstrated a favorable effect on outcomes, and cardiac telerehabilitation (CTR) could represent an innovative healthcare delivery model. The aim of our review is to study how technologies used in rehabilitation have changed over time and also to understand what types of rehabilitation programs have been used in telerehabilitation. Methods: We searched randomized controlled trials (RCTs) in three electronic databases, PubMed, Web of Science, and Scopus, from January 2015 to January 2024, using relevant keywords. Initially, 502 articles were found, and 79 duplicates were identified and eliminated with EndNote. Results: In total, 16 RCTs fulfilled the pre-defined criteria, which were analyzed in our systematic review. The results showed that after CTR, there was a significant improvement in main outcome measures, as well as in relation to technological advances. Conclusions: Moreover, compared to center-based rehabilitation, CTR can offer further advantages, with better cost-effectiveness, the breakdown of geographical barriers, and the improvement of access to treatment for the female population, which is traditionally more socially committed.
Assessment of Knowledge, Attitudes, and Vaccination Practices Regarding the New RSV Vaccine among Health Professionals in Greece
Authors: Papagiannis Dimitrios , Tiganis Nikolaos , Kotsiou Ourania S. , Lampropoulos Ioannis C. , Fradelos Evangelos C. , Malli Foteini , Gourgoulianis Konstantinos I.
Published: August 2024

The introduction of a new vaccine into immunization programs represents a significant advancement in the global effort to combat vaccine-preventable diseases. Data from the World Health Organization support that immunization prevents between 2 and 3 million deaths each year across various diseases, underscoring its pivotal role in global health. The present study aims to assess the knowledge, attitudes, and anticipated vaccination practices among health professionals in Central Greece in response to the potential introduction of new Respiratory Syncytial Virus (RSV) vaccination guidelines by the National Vaccines Committee. Among the 450 health professionals solicited for the study, 219 provided responses, yielding a response rate of approximately 55%. A substantial majority (70.3%) accurately identified the vaccine’s current availability, and 62.1% were aware of the current recommendation for RSV vaccination in pregnant women. In response to whether health professionals support the inclusion of an RSV vaccine in the national vaccination program if it becomes commercially available and is recommended by the Greek National Immunization Program, general practitioners showed the most support, with an average score of 4.86 (95% CI, 4.69–5.00), followed by pediatricians at 4.76 (95% CI, 4.63–4.89), pulmonologists at 4.68 (95% CI, 4.36–5.00), and obstetricians at 4.33 (95% CI, 3.95–4.71). Concerning general opinions on vaccinations, a high level of agreement was noted among the majority of health professionals, excluding nurses. Pharmacists recorded the highest agreement, with a perfect score of 5 (CI, 5.00–5.00), followed closely by pediatricians at 4.99 (CI, 4.97–5.00), GPs at 4.95 (CI, 4.85–5.00), pulmonologists at 4.93 (CI, 4.83–5.00), obstetricians at 4.74 (CI, 4.42–5.00), and nurses at 3.80 (CI, 3.06–4.54). A tailored approach to education is needed to ensure that healthcare professionals can communicate more effectively about RSV risks and vaccination benefits, fostering a proactive stance towards disease prevention and patient care. In essence, our study underscores the importance of knowledge in shaping a compassionate and responsive healthcare environment, ready to meet the challenges of RSV head-on.
Total Soluble Solid Content and Nutritional Values of Sotol (Dasylirion leiophyllum) in the Chihuahuan Desert as Affected by Rainy Season and Topography
Authors: Juárez-Morales Martín , Martínez-Salvador Martín , Chávez-Mendoza Celia , Villarreal-Guerrero Federico , Santellano-Estrada Eduardo , Pinedo-Alvarez Alfredo , Corrales-Lerma Raúl , Hernández-Quiroz Nathalie S. , Vázquez-Quintero Griselda , Vega-Mares José H.
Published: August 2024

Sotol (Dasylirion leiophyllum) grows in the Chihuahan Desert in the north of Mexico and south of the United States. The stem of this species is used to produce a liquor widely known as sotol. A field sampling and a laboratory analysis were carried out to determine the influence of the rainy season, altitude, topography, and aspect over the soluble solid content (°Brix) and bromatological variables of mature plants of sotol in Chihuahua, Mexico. Analyses of variance and Tukey tests were performed. The rainy season and altitude showed significant statistical influence (p ≤ 0.05) on the total soluble solids content; meanwhile, only altitude showed a significant effect on the bromatological variables (p ≤ 0.05). According to the results of the Tukey tests (p < 0.05), sotol plants have the highest concentrations of soluble solid contents before the rainy season (25 °Brix) and at sites with altitudes lower than 1300 m (25.95 °Brix). In addition, the means of raw protein and carbohydrates content were the highest in plants living at altitudes lower than 1500 m, at 1.93% and 31.74%, respectively. Meanwhile, topography, aspect, and the interactions of the evaluated factors did not show significant influence (p ≤ 0.05) over the total soluble solid content, nor over the bromatological variables studied.
Dual Use of Cannabis with Tobacco Is Associated with Increased Sugary Food and Drink Intake in Young People
Authors: Malhotra Niamh , Kasaraneni Nikita , Ahadian Zoya , Chang Howard , Advani Ira , McDermott Jade , Truong Caitlyn , Gaboyan Samvel , Mittal Ankita , Perryman Alexia , Masso-Silva Jorge A. , Steeger Christine M. , Bowler Russell P. , Castaldi Peter J. , Sharma Sunita , Crotty Alexander Laura E.
Published: August 2024

Rates of cannabis initiation among teenagers and young adults are increasing. Further, the use of various forms of cannabis (smoked or vaped) with nicotine (dual use) is increasingly common among young people. The health effects of dual use are lesser known, particularly in the context of high-potency cannabis products and across different routes of administration, which is ominous in terms of predicting future health outcomes. There is a long history of cannabis use being associated with decreased activity and increased snacking, both of which could portend an increased risk of metabolic and cardiovascular disease, particularly when these habits begin during formative years. However, modern forms of cannabis may not have these same effects. Here, we assess whether cannabis use alone and dual use of cannabis with nicotine impact dietary and exercise habits in young people. An anonymous, social media-based survey was designed based on the UC San Diego Inhalant Questionnaire and published diet and exercise questionnaires. A total of 457 surveys were completed. Young sole cannabis users represented 29% of responders, 16% were dual users of cannabis and nicotine, and 55% were non-users of either drug. Although the sole use of cannabis was not associated with dietary or activity differences relative to non-users, dual users of cannabis and nicotine reported higher consumption of unhealthy sugars. This novel finding of dual use being associated with increased sugar intake in young people raises concerns for an increased risk of metabolic syndrome and cardiovascular disease in this population.
Exploring Community Perspectives on Functional Paediatric Habitual Constipation
Authors: Al Khashram Nawaf , Al Abdulqader Ahmad A. , Alarfaj Haytham Mohammed , Bu Bshait Mohammed Saad , Kamal Ahmed Hassan , Zakaria Ossama M. , Albarqi Mohammed Nasser , Almulhim Mohannad Adnan , Almousa Mazin Abdulwahab , Almaqhawi Abdullah
Published: August 2024

(1) Background: Functional habitual constipation (FC) in children is a common gastrointestinal problem. This study aimed to explore the local community’s view on this problem, emphasising the challenges that parents face in managing the condition and its impact on the child’s quality of life. (2) Methods: A prospective, cross-sectional, community-based study was conducted between March and July 2023. The survey received 933 responses. The target population was adults over 18 years of age living in the Eastern Province of Saudi Arabia. An electronically distributed questionnaire was designed in the Arabic language. (3) Results: The mean knowledge scores were significantly higher in females than males, with t (931) = −2.701 and p = 0.007. The Bonferroni post hoc test results indicated that participants between 20 and 29 years exhibited significantly higher levels of knowledge scores compared to those between 30 and 39 years. Furthermore, the results revealed that those with three or more children had significantly higher knowledge scores compared to those with only one child. (4) Conclusions: This study demonstrated that parents in the local community have a good perceived knowledge of FC, but it needs to be linked with practice. They tended to report high levels of perception and demonstrated better practices. These results emphasise the importance of exploring the local community’s view on constipation among children.
Music Therapy with Preterm Infants and Their Families after Hospital Discharge: An Integrative Review
Authors: Clemencic-Jones Verena , Trajkovski Suza , Fuller Allison , Mattock Karen , Stulz Virginia
Published: August 2024

After discharge from a neonatal unit, families of preterm infants may require therapeutic support to address challenges related to their infant/s’ development, changed family circumstances, and/or parent wellbeing. This integrative review (IR) sought to examine the impact of music therapy on preterm infants and their families post-hospital discharge. A systematic search encompassing seven databases resulted in 83 citations, with six studies initially meeting the inclusion criteria. A further six studies were evaluated and selected upon their publication during the review process. Each study was assessed using the Mixed Methods Appraisal Tool (MMAT), followed by the identification of major themes and sub-themes. Our results suggest that music therapy contributed to creating supportive physical and metaphorical environments for preterm infants and their families, in which they could acquire essential skills, tools, and resources for fostering communication and connection with one another. Preterm infants and toddlers may have also enhanced their developmental skills through music therapy sessions post-discharge. Further investigation into the impact of music therapy on preterm infants and their caregivers at different timepoints after hospital discharge is recommended, as well as a comparison of individual and group music therapy outcomes on infant development and parent health. Future research should include a broader spectrum of family members, along with caregivers from diverse family structures and gender identities, reflecting practices already established in some clinical settings.
The Genetic Profile of Combat Sport Athletes: A Systematic Review of Physiological, Psychological and Injury Risk Determinants
Authors: Anastasiou Konstantinos , Morris Mhairi , Akam Liz , Mastana Sarabjit
Published: August 2024

This systematic review aims to assess the genetic determinants influencing combat sports performance and address potential gaps in previous reviews. Twenty-four selected studies were analysed, investigating genetic influences on physiological performance, psychological traits, psychophysiological factors like pain perception, and injury susceptibility in combat sport athletes. The systematic literature search, using keywords, encompassed PubMed, Scopus, SportDiscus, Medline, and Google Scholar. The Covidence systematic review management software facilitated the screening process and the creation of the PRISMA flow diagram. The quality assessment complied with the PRISMA guidelines, featuring a custom 10-point scale and the STREGA criteria for more reliable study inclusion. Collectively, the 24 studies incorporated 18,989 participants, of which 3323 were combat athletes of majority European ancestry (71.7%) from various combat sports disciplines. Twenty-five unique genetic variants were significantly associated with combat sports performance across diverse domains. These included physiological performance (nine genetic variants), psychological traits (ten genetic variants), psychophysiological factors (one genetic variant), and injury susceptibility (four genetic variants). In conclusion, this systematic review lays the foundation for a more comprehensive exploration of the association between genetics and athletic performance in the demanding arena of combat sports, offering valuable insights for talent identification, training optimisation, and injury prevention.
Abortion Incidence among Young Women in Urban Slums and Non-Slums in Kinshasa, DR Congo
Authors: Nkombondo Glory B. , Kabasubabo Francis K. , Akilimali Pierre Z.
Published: August 2024

Background: Worldwide, around 73 million induced abortions take place every year. Of these, 45% are unsafe and can lead to complications. The evolution of the legal and practical landscape of abortion in the Democratic Republic of the Congo (DRC) over the last few years necessitates a re-examination of the experience of induced abortion, leading this study to measure the incidence of abortion among young women (15 to 29 years of age), as well as the heterogeneity of this problem according to the residence of these young women (slum vs. non-slum areas). Methodology: We used representative survey data on women aged 15–49 in Kinshasa, collected from December 2021 to April 2022. The survey included questions about the respondents’ and their closest confidants’ experience of induced abortion, including the methods and sources used. We estimated abortion incidence and heterogeneity over one year based on residence in the city of Kinshasa according to sociodemographic characteristics. Results: The fully adjusted one-year friend abortion rate in 2021 was 131.5 per 1000 (95% CI: IQR 99.4–163.6). These rates were significantly higher than the corresponding estimates of respondents. The incidence of induced abortion for respondents was 24.4 per 1000 (95% CI: 15.8–32.9) abortions per 1000 women. The incidence rates of induced abortion were much higher among the respondents residing in slums than among those residing in non-slums (29.2 vs. 13.0 per 1000; p < 0.001). Slum respondents indicated higher use of non-recommended methods than non-slum respondents. Conclusions: More precise estimates of the incidence of abortion indicate that the incidence rate of abortion was higher among young women residing in slums who were unmarried and had no children. These incidences were higher among confidants than among respondents. There is still a lot of work to be done to fulfill the obligations outlined in the Maputo Protocol. The aim is to decrease the occurrence of unsafe abortions and their associated effects.
Duodenal Fluid Analysis as a Rewarding Approach to Detect Low-Abundance Mutations in Biliopancreatic Cancers
Authors: Tavano Francesca , Latiano Anna , Palmieri Orazio , Gioffreda Domenica , Latiano Tiziana , Gentile Annamaria , Tardio Matteo , Latiano Tiziana Pia , Gentile Marco , Terracciano Fulvia , Perri Francesco
Published: August 2024

Diagnosis of biliopancreatic cancers by the available serum tumor markers, imaging, and histopathological tissue specimen examination remains a challenge. Circulating cell-free DNA derived from matched pairs of secretin-stimulated duodenal fluid (DF) and plasma from 10 patients with biliopancreatic diseases and 8 control subjects was analyzed using AmpliSeq™ HD technology for Ion Torrent Next-Generation Sequencing to evaluate the potential of liquid biopsy with DF in biliopancreatic cancers. The median cfDNA concentration was greater in DF-derived than in plasma-derived samples. A total of 13 variants were detected: 11 vs. 1 were exclusive for DF relative to the plasma source, and 1 was shared between the two body fluids. According to the four-tier systems, 10 clinical tier-I–II (76.9%), 1 tier–III (7.7%), and 2 tier–IV (15.4%) variants were identified. Notably, the 11 tier-I-III variants were exclusively found in DF-derived cfDNA from five patients with biliopancreatic cancers, and were detected in seven genes (KRAS, TP53, BRAF, CDKN2A, RNF43, GNAS, and PIK3CA); 82% of the tier-I-III variants had a low abundance, with a VAF < 6%. The mutational profiling of DF seems to be a reliable and promising tool for identifying cancer-associated alterations in malignant cancers of the biliopancreatic tract.
Immunohistochemistry Screening of Different Tyrosine Kinase Receptors in Canine Solid Tumors—Part I: Proposal of a Receptor Panel to Predict Therapies
Authors: Dos Anjos Denner Santos , Civa Patrick Antônio Sonaglio , Werner Juliana , Vicente Igor Simões Tiagua , Fonseca-Alves Carlos Eduardo
Published: August 2024

The use of tyrosine kinase inhibitors (TKI) has been growing in veterinary oncology and in the past few years several TKI have been tested in dogs. However, different from human medicine, we lack strategies to select patients to be treated with each TKI. Therefore, this study aimed to screen different tumor subtypes regarding TKI target immunoexpression as a predictor strategy to personalize the canine cancer treatment. It included 18 prostatic carcinomas, 36 soft tissue sarcomas, 20 mammary gland tumors, 6 urothelial bladder carcinomas, and 7 tumors from the endocrine system. A total of 87 patients with paraffin blocks were used to perform immunohistochemistry (IHC) of human epidermal growth factor receptor 2 (HER-2), epidermal growth factor receptors 1 (EGFR1), vascular endothelial growth factor receptor 2 (VEGFR-2), platelet derived growth factor receptor beta (PDGFR-β), c-KIT, and extracellular signal-regulated kinase 1/2 (ERK1/ERK2). The immunohistochemical screening revealed a heterogeneous protein expression among histological types with mesenchymal tumors showing the lowest expression level and carcinomas the highest expression. We have demonstrated by IHC screening that HER2, EGFR1, VEGFR-2, PDGFR-β and ERK1/ERK2 are commonly overexpressed in dogs with different carcinomas, and KIT expression is considered relatively low in the analyzed samples.
Inflammation and Colorectal Cancer: A Meta-Analysis of the Prognostic Significance of the Systemic Immune–Inflammation Index (SII) and the Systemic Inflammation Response Index (SIRI)
Authors: Menyhart Otilia , Fekete János Tibor , Győrffy Balázs
Published: August 2024

The overall prognosis for colorectal cancer (CRC) remains challenging as the survival time varies widely, even in patients with the same stage of disease. Recent studies suggest prognostic relevance of the novel markers of systemic inflammation, the systemic immune–inflammation index (SII), and the systemic inflammation response index (SIRI). We conducted a comprehensive meta-analysis to assess the prognostic significance of the SII and the SIRI in CRC. We searched the relevant literature for observational studies, and random effects models were employed to conduct a statistical analysis using the metaanalysisonline.com platform. Pooled effect sizes were reported with hazard ratios (HRs) and corresponding 95% confidence intervals (CI). Data from 29 studies published between 2016 and 2024, comprising 10,091 participants, were included in our meta-analysis on SII. CRC patients with high SII levels had worse disease outcomes, which were associated with poor OS (HR: 1.75; 95% CI: 1.4–2.19) and poor PFS/DFS/RFS (HR: 1.25; 95% CI: 1.18–1.33). This increased risk of worse OS was present irrespective of the treatment strategy, sample size (<220 and ≥220), and cutoff used to define high and low SII (<550 and ≥550) groups. Based on data from five studies comprising 2362 participants, we found a strong association between the high SIRI and worse OS (HR: 2.65; 95% CI: 1.6–4.38) and DFS/RFS (HR: 2.04; 95% CI: 1.42–2.93). According to our results, both the SII and SIRI hold great promise as prognostic markers in CRC. Further validations are needed for their age- and stage-specific utility in the clinical routine.
Identification and Functional Studies on the Role of PlSPL14 in Herbaceous Peony Stem Development
Authors: Xu Huajie , Yu Renkui , Tang Yuhan , Meng Jiasong , Tao Jun
Published: August 2024

Stem strength plays a crucial role in the growth and development of plants, as well as in their flowering and fruiting. It not only impacts the lodging resistance of crops, but also influences the ornamental value of ornamental plants. Stem development is closely linked to stem strength; however, the roles of the SPL transcription factors in the stem development of herbaceous peony (Paeonia lactiflora Pall.) are not yet fully elucidated. In this study, we obtained and cloned the full-length sequence of PlSPL14, encoding 1085 amino acids. Quantitative real-time PCR (qRT-PCR) analysis revealed that the expression level of PlSPL14 gradually increased with the stem development of P. lactiflora and was significantly expressed in vascular bundles. Subsequently, utilizing the techniques of virus-induced gene silencing (VIGS) and heterologous overexpression in tobacco (Nicotiana tabacum L.), it was determined that PlSPL14-silenced P. lactiflora had a thinner xylem thickness, a decreased stem diameter, and weakened stem strength, while PlSPL14-overexpressing tobacco resulted in a thicker xylem thickness, an increased stem diameter, and enhanced stem strength. Further screening of the interacting proteins of PlSPL14 using a yeast two-hybrid (Y2H) assay revealed an interactive relationship between PlSPL14 and PlSLR1 protein, which acts as a negative regulator of gibberellin (GA). Additionally, the expression level of PlSLR1 gradually decreased during the stem development of P. lactiflora. The above results suggest that PlSPL14 may play a positive regulatory role in stem development and act in the xylem, making it a potential candidate gene for enhancing stem straightness in plants.
Radiation-Induced miRNAs Changes and cf mtDNA Level in Trauma Surgeons: Epigenetic and Molecular Biomarkers of X-ray Exposure
Authors: Kussainova Assiya , Aripova Akmaral , Ibragimova Milana , Bersimbaev Rakhmetkazhi , Bulgakova Olga
Published: August 2024

Exposure to ionizing radiation can result in the development of a number of diseases, including cancer, cataracts and neurodegenerative pathologies. Certain occupational groups are exposed to both natural and artificial sources of radiation as a consequence of their professional activities. The development of non-invasive biomarkers to assess the risk of exposure to ionizing radiation for these groups is of great importance. In this context, our objective was to identify epigenetic and molecular biomarkers that could be used to monitor exposure to ionizing radiation. The impact of X-ray exposure on the miRNAs profile and the level of cf mtDNA were evaluated using the RT-PCR method. The levels of pro-inflammatory cytokines in their blood were quantified using the ELISA method. A significant decrease in miR-19a-3p, miR-125b-5p and significant increase in miR-29a-3p was observed in the blood plasma of individuals exposed to X-ray. High levels of pro-inflammatory cytokines and cf mtDNA were also detected. In silico identification of potential targets of these miRNAs was conducted using MIENTURNET. VDAC1 and ALOX5 were identified as possible targets. Our study identified promising biomarkers such as miRNAs and cf mtDNA that showed a dose-dependent effect of X-ray exposure.
Comparative In Vitro Study between Biocompatible Chitosan-Based Magnetic Nanocapsules and Liposome Formulations with Potential Application in Anti-Inflammatory Therapy
Authors: Vochița Gabriela , Cadinoiu Anca Niculina , Rață Delia-Mihaela , Atanase Leonard Ionuț , Popa Marcel , Mahdieh Athar , Mihai Cosmin-Teodor , Stache Alexandru-Bogdan , Moldovan Cristina-Veronica , Băcăiţă Elena Simona , Condriuc Iustina Petra , Gherghel Daniela
Published: August 2024

This study describes the comparison between the interaction of a series of peptide-functionalized chitosan-based nanocapsules and liposomes with two cell lines, i.e., mouse macrophages RAW 264.7 and human endothelial cells EA.hy926. Both types of nanocarriers are loaded with magnetic nanoparticles and designed for anti-inflammatory therapy. The choice of these magnetic nanostructures is argued based on their advantages in terms of size, morphology, chemical composition, and the multiple possibilities of modifying their surface. Moreover, active targeting might be ensured by using an external magnetic field. To explore the impact of chitosan-based nanocapsules and liposomes on cell cytophysiology, the cell viability, using the MTT assay, and cell morphology were investigated. The results revealed low to moderate cytotoxicity of free nanocapsules and significant cytotoxicity induced by chitosan-coated liposomes loaded with dexamethasone, confirming its release from the delivery system. Thus, after 48 h of treatment with nanocapsules, the viability of RAW 264.7 cells varied between 88.18% (OCNPM-1I, 3.125 µg/mL) and 76.37% (OCNPM-1, 25 µg/mL). In the same conditions, EA.hy926 cell viability was between 99.91% (OCNPM-3, 3.125 µg/mL) and 75.15% (OCNPM-3, 25 µg/mL) at the highest dose (25 µg/mL), the values being comparable for both cell lines. Referring to the cell reactivity after dexamethasone-loaded liposome application, the lowest viability of RAW 264.7 cells was 41.25% (CLDM5CP-1, 25 µg/mL) and 58.20% (CLDMM2CP-1 1.25 µg/mL) in the endothelial cell line, proving a selective character of action of nanocarriers. The cell morphology test, performed to support and confirm the results obtained by the MTT test, revealed a differentiated response for the two types of nano-carriers. As expected, an intense cytotoxic effect in the case of dexamethasone-loaded liposomes and a lack of cytotoxicity for drug-free nanocapsules were noticed. Therefore, our study demonstrated the biocompatible feature of the studied nanocarriers, which highlights them for future research as potential drug delivery systems for pharmacological applications, including anti-inflammatory therapy.
The Antioxidant and HDAC-Inhibitor α-Lipoic Acid Is Synergistic with Exemestane in Estrogen Receptor-Positive Breast Cancer Cells
Authors: Pradel Laura S. , Ho Yu-Lin , Gohlke Holger , Kassack Matthias U.
Published: August 2024

Anti-estrogenic therapy is established in the management of estrogen receptor (ER)-positive breast cancer. However, to overcome resistance and improve therapeutic outcome, novel strategies are needed such as targeting widely recognized aberrant epigenetics. The study aims to investigate the combination of the aromatase inhibitor exemestane and the histone deacetylase (HDAC) inhibitor and antioxidant α-lipoic acid in ER-positive breast cancer cells. First, the enantiomers and the racemic mixture of α-lipoic acid, and rac-dihydro-lipoic acid were investigated for HDAC inhibition. We found HDAC inhibitory activity in the 1–3-digit micromolar range with a preference for HDAC6. Rac-dihydro-lipoic acid is slightly more potent than rac-α-lipoic acid. The antiproliferative IC50 value of α-lipoic acid is in the 3-digit micromolar range. Notably, the combination of exemestane and α-lipoic acid resulted in synergistic behavior under various incubation times (24 h to 10 d) and readouts (MTT, live-cell fluorescence microscopy, caspase activation) analyzed by the Chou–Talalay method. α-lipoic acid increases mitochondrial fusion and the expression of apoptosis-related proteins p21, APAF-1, BIM, FOXO1, and decreases expression of anti-apoptotic proteins survivin, BCL-2, and c-myc. In conclusion, combining exemestane with α-lipoic acid is a promising novel treatment option for ER-positive breast cancer.
Modulation of Breast Cancer Cell Apoptosis and Macrophage Polarization by Mistletoe Lectin in 2D and 3D Models
Authors: Hong Chang-Eui , Lyu Su-Yun
Published: August 2024

Korean mistletoe (Viscum album L. var. coloratum) is renowned for its medicinal properties, including anti-cancer and immunoadjuvant effects. This study aimed to elucidate the mechanisms by which Korean mistletoe lectin (V. album L. var. coloratum agglutinin; VCA) modulates breast cancer cell apoptosis and macrophage polarization. The specific objectives were to (1) investigate the direct effects of VCA on MCF-7 breast cancer cells and THP-1-derived M1/M2 macrophages; (2) analyze the impact of VCA on the paracrine interactions between these cell types; and (3) compare the efficacy of VCA in 2D vs. 3D co-culture models to bridge the gap between in vitro and in vivo studies. We employed both 2D and 3D models, co-culturing human M1/M2 macrophages with human MCF-7 breast cancer cells in a Transwell system. Our research demonstrated that M1 and M2 macrophages significantly influenced the immune and apoptotic responses of breast cancer cells when exposed to VCA. M1 macrophages exhibited cytotoxic characteristics and enhanced VCA-induced apoptosis in both 2D and 3D co-culture models. Conversely, M2 macrophages initially displayed a protective effect by reducing apoptosis in breast cancer cells, but this protective effect was reversed upon exposure to VCA. Furthermore, our findings illustrate VCA’s ability to modulate M1 and M2 polarization in breast cancer cells. Finally, the use of magnetic 3D cell cultures suggests their potential to yield results comparable to conventional 2D cultures, bridging the gap between in vitro and in vivo studies.
Exosomal Preconditioning of Human iPSC-Derived Cardiomyocytes Beneficially Alters Cardiac Electrophysiology and Micro RNA Expression
Authors: Røsand Øystein , Wang Jianxiang , Scrimgeour Nathan , Marwarha Gurdeep , Høydal Morten Andre
Published: August 2024

Experimental evidence, both in vitro and in vivo, has indicated cardioprotective effects of extracellular vesicles (EVs) derived from various cell types, including induced pluripotent stem cell-derived cardiomyocytes. The biological effects of EV secretion, particularly in the context of ischemia and cardiac electrophysiology, remain to be fully explored. Therefore, the goal of this study was to unveil the effects of exosome (EXO)-mediated cell–cell signaling during hypoxia by employing a simulated preconditioning approach on human-induced pluripotent stem cell-derived cardiomyocytes (hIPSC-CMs). Electrophysiological activity of hIPSC-CMs was measured using a multielectrode array (MEA) system. A total of 16 h of hypoxic stress drastically increased the beat period. Moreover, hIPSC-CMs preconditioned with EXOs displayed significantly longer beat periods compared with non-treated cells after 16 h of hypoxia (+15.7%, p < 0.05). Furthermore, preconditioning with hypoxic EXOs resulted in faster excitation–contraction (EC) coupling compared with non-treated hIPSC-CMs after 16 h of hypoxia (−25.3%, p < 0.05). Additionally, microRNA (miR) sequencing and gene target prediction analysis of the non-treated and pre-conditioned hIPSC-CMs identified 10 differentially regulated miRs and 44 gene targets. These results shed light on the intricate involvement of miRs, emphasizing gene targets associated with cell survival, contraction, apoptosis, reactive oxygen species (ROS) regulation, and ion channel modulation. Overall, this study demonstrates that EXOs secreted by hIPSC-CM during hypoxia beneficially alter electrophysiological properties in recipient cells exposed to hypoxic stress, which could play a crucial role in the development of targeted interventions to improve outcomes in ischemic heart conditions.
Natural Products in the Treatment of Retinopathy of Prematurity: Exploring Therapeutic Potentials
Authors: Heo Jong-Ik , Ryu Juhee
Published: August 2024

Retinopathy of prematurity (ROP) is a vascular disorder affecting the retinas of preterm infants. This condition arises when preterm infants in incubators are exposed to high oxygen levels, leading to oxidative stress, inflammatory responses, and a downregulation of vascular endothelial growth factors, which causes the loss of retinal microvascular capillaries. Upon returning to room air, the upregulation of vascular growth factors results in abnormal vascular growth of retinal endothelial cells. Without appropriate intervention, ROP can progress to blindness. The prevalence of ROP has risen, making it a significant cause of childhood blindness. Current treatments, such as laser therapy and various pharmacologic approaches, are limited by their potential for severe adverse effects. Therefore, a deeper understanding of ROP’s pathophysiology and the development of innovative treatments are imperative. Natural products from plants, fungi, bacteria, and marine organisms have shown promise in treating various diseases and have gained attention in ROP research due to their minimal side effects and wide-ranging beneficial properties. This review discusses the roles and mechanisms of natural products that hold potential as therapeutic agents in ROP management.
Herpes Simplex Virus Type 1 Infection of Human Periodontal Ligament
Authors: Ortis Morgane , Chevalier Marlène , Olivieri Charles-Vivien , Vitale Sébastien , Paul Adrien , Tonoyan Lilit , Doglio Alain , Marsault Robert
Published: August 2024

The periodontal ligament (PDL) is a complex connective tissue that connects the tooth root to the dental alveolar bone and plays crucial mechanical roles. PDL also exhibits regenerative roles and regulatory functions to maintain periodontium integrity and homeostasis. While PDL exposure to oral microbial pathogens is common, virtually nothing is known regarding viral infections of PDL. In particular, human herpes simplex virus type 1 (HSV-1) persistently infects the oral cavity through infections of the oral epithelium, connective tissue and neurons. While the oral spread of HSV-1 is generally asymptomatic, this virus has also been implicated in various oral pathologies. In this study, using a primary cell model derived from PDL (PDL cells), and whole surgical fragments of PDL, we provide evidence supporting the efficient infection of PDL by HSV-1 and the promotion of cytopathic effects. Infection of PDL by HSV-1 was also associated with an acute innate inflammatory response, as illustrated by the production of antiviral interferons and pro-inflammatory cytokines. Furthermore, this inflammatory response to HSV-1 was exacerbated in the presence of bacterial-derived products, such as peptidoglycans. This work therefore highlights the ability of HSV-1 to infect mesenchymal cells from PDL, suggesting that PDL may serve as a viral reservoir for the periodontal spread of HSV-1. Moreover, this raises questions about HSV-1 oral pathogenesis, as HSV-1-associated cytopathic and inflammatory effects may contribute to profound alterations of PDL integrity and functioning.
Responsible Automation: Exploring Potentials and Losses through Automation in Human–Computer Interaction from a Psychological Perspective
Authors: Diefenbach Sarah , Ullrich Daniel , Lindermayer Tim , Isaksen Kaja-Lena
Published: August 2024

Robots and smart technologies are becoming part of everyday life and private households. While this automation of mundane tasks typically creates pragmatic benefits (e.g., efficiency, accuracy, time savings), it may also come with psychological losses, such as in meaning, competence, or responsibility. Depending on the domain (e.g., AI-assisted surgery, automated decision making), especially the user’s felt responsibility could have far-reaching consequences. The present research systematically explores such effects, building a more structured base for responsible automation in human–computer interaction (HCI). Based on a framework of seven dimensions, study 1 (N = 122) evaluates users’ reflections on automating five mundane tasks (e.g., gardening, paperwork) and identifies reasons for or against automation in different domains (e.g., creativity, care work, decision making). Study 2 (N = 57) provides deeper insights into effects of automation on responsibility perceptions. Based on the example of a vacuum cleaner robot, an experimental laboratory study contrasted a non-robotic manual vacuum cleaner to a robot, whereby the user’s perceptions of device agency (higher for the robot) and own competence (higher for the manual device) were central mediators for the perceived responsibility for the result. We position our findings as part of a broader idea of responsible design and automation from a user-centered design perspective.
Safe Coverage Control of Multi-Agent Systems and Its Verification in ROS/Gazebo Environment
Authors: Siri Fidelia Chaitra , Song Jie , Svinin Mikhail
Published: August 2024

This paper presents safe coverage control algorithms for multi-agent systems, integrating Centroidal Voronoi Tessellation (CVT) and control barrier functions (CBFs). This study aims to ensure safety and spatial optimization by combining CVT and CBFs for obstacle avoidance, testing the controller through simulations, and verifying the results with RT mobile robots. This development of safe coverage control algorithms for multi-agent systems achieves a synergy that addresses both safety and spatial optimization, which are crucial for multi-agent systems. The proposed CVT-CBF-based controller has been validated through extensive simulations in the ROS/Gazebo environment and physical experiments with RT robots, demonstrating its effectiveness in achieving collision-free coverage. This study provides a comprehensive understanding of the integration of CVT and CBFs for safe coverage control with obstacle avoidance in multi-agent systems, highlighting both its potential and the necessary considerations for practical deployment.
A Transcriptome Analysis of Poncirus trifoliata, an Aurantioideae Species Tolerant to Asian Citrus Psyllid, Has Identified Potential Genes and Events Associated with Psyllid Resistance
Authors: Wang Xinyou , Ji Haoran , Zhong Leijian , Zeng Wei , Ouyang Zhigang , Li Ruimin
Published: August 2024

Citrus huanglongbing (HLB) is a devastating disease for citrus production, largely caused by the Asian citrus psyllid (ACP). Poncirus trifoliata exhibits high resistance to ACP; however, this resistance is weakened when C. sinensis is co-cultivated. This study aimed to identify the differentially expressed genes (DEGs) during ACP feeding and to uncover potential ACP resistance genes in P. trifoliata. In comparison to independent cultivation, 1247 and 205 DEGs were identified in P. trifoliata when co-cultivated with C. sinensis after 7 and 14 days, respectively. Analysis of enriched Gene Ontology categories revealed that DEGs were significantly associated with the cell wall, glucometabolic activities, and secondary metabolites. Additionally, these genes were found to be involved in phytohormone signaling, cell wall metabolism, redox state homeostasis, and secondary metabolites, as well as a number of transcription factor genes (TFs). Furthermore, we examined the impact of the ACP feeding factor on the gene expression patterns in P. trifoliata. Results showed an increase in the JA signaling pathway and various TFs. The RNA-seq results were verified using reverse transcription quantitative PCR. Our findings shed light on the molecular basis of ACP resistance in P. trifoliata and identified potential genes associated with this resistance.
Correlation between the Long Head of the Biceps Microscopic Degeneration and Extent of Apoptotic Process
Authors: Jaworski Łukasz , Zabrzyński Jan , Millett Peter J. , Rupp Marco-Christopher , Familiari Filippo , Huri Gazi , Erdmann Jakub , Błachowski Michał , Pękala Przemysław , Gagat Maciej
Published: August 2024

Objectives: The purpose of this study was to determine the correlation between microscopic degeneration in the long head of the biceps tendon (LHBT) and the apoptotic process. Methods: This study included 26 consecutive patients who had undergone arthroscopic biceps tenodesis or tenotomy for symptomatic LHBT with or without concomitant rotator cuff tears (RCTs). Histological examination of the specimens under a light microscope was conducted after staining with hematoxylin, eosin, and the Alcian blue. Histopathological changes were assessed using the original Bonar score and the modified Bonar score and then correlated with the expression of the subsequent apoptosis markers: activated caspase-3 (casp3), tumor protein p53 (p53), and B-cell lymphoma 2 (BCL-2). Results: The mean original Bonar score was 8.65 (range 5–11), while the modified Bonar score was 7.61. There was no correlation between the original Bonar score and the age of the patients, but a positive correlation was found between the modified Bonar score and the age of the patients (p = 0.0022). There was no correlation between the age of patients and the expression indexes of BCL-2 and casp3. However, the expression of the p53 index showed a positive correlation with patient aging (p = 0.0441). Furthermore, there was no correlation observed between the expression of apoptotic indexes and both the original and modified Bonar scale. Conclusions: In LHB tendinopathy, the expression of apoptosis does not seem to directly correlate with the extent of degeneration, particularly in the late stages of tendinopathy. However, the transformations observed in collagen and ground substance were significantly associated with age, as well as tendinous tissue degeneration quantified according to modified Bonar score. The age of patients was also linked with the expression of the p53 index, as an increased apoptosis in the studied population.
Innovative Biomaterials: The Cornerstone of Next-Generation Medical Solutions
Authors: Scheau Cristian , Didilescu Andreea Cristiana , Caruntu Constantin
Published: August 2024

Over the past decade, 3D printing has gained traction in the medical field, and research has started to concentrate on discovering and developing new printing techniques and novel materials usable in this complex field [...]
A Hybrid Fuzzy LQR-PI Blade Pitch Control Scheme for Spar-Type Floating Offshore Wind Turbines
Authors: Ma Ronglin , Siaw Fei Lu , Thio Tzer Hwai Gilbert
Published: August 2024

Floating offshore wind turbines (FOWTs) experience unbalanced loads and platform motion due to the coupling of variable wind and wave loads, which leads to output power fluctuation and increased fatigue loads. This paper introduces a new blade pitch control strategy for FOWTs that combines fuzzy logic with a linear quadratic regulator (LQR) and a proportional-integral (PI) controller. The fuzzy PI controller dynamically adjusts the PI control gains to regulate rotor speed and stabilize output power. Fuzzy LQR is employed for individual pitch control, utilizing fuzzy logic to adaptively update feedback gains to achieve stable power output, suppress platform motion, and reduce fatigue load. Co-simulations conducted with OpenFAST (Fatigue, Aerodynamics, Structures, and Turbulence) and MATLAB/Simulink under diverse conditions demonstrate the superiority of the proposed method over traditional PI control. The results show significant reductions in platform pitch, roll, and heave motion by 17%, 27%, and 48%, respectively; blade out-of-plane, pitch, and flapwise bending moments are reduced by 38%, 44%, and 36%; and the tower base roll and pitch bending moments are reduced by up to 29% and 22%, respectively. The proposed control scheme exhibits exceptional environmental adaptability, enhancing FOWT’s power regulation, platform stability, and reliability in complex marine environments.
Bayesian Rare Variant Analysis Identifies Novel Schizophrenia Putative Risk Genes
Authors: Han Shengtong
Published: August 2024

The genetics of schizophrenia is so complex that it involves both common variants and rare variants. Rare variant association studies of schizophrenia are challenging because statistical methods for rare variant analysis are under-powered due to the rarity of rare variants. The recent Schizophrenia Exome meta-analysis (SCHEMA) consortium, the largest consortium in this field to date, has successfully identified 10 schizophrenia risk genes from ultra-rare variants by burden test, while more risk genes remain to be discovered by more powerful rare variant association test methods. In this study, we use a recently developed Bayesian rare variant association method that is powerful for detecting sparse rare risk variants that implicates 88 new candidate risk genes associated with schizophrenia from the SCHEMA case–control sample. These newly identified genes are significantly enriched in autism risk genes and GO enrichment analysis indicates that new candidate risk genes are involved in mechanosensory behavior, regulation of cell size, neuron projection morphogenesis, and plasma-membrane-bounded cell projection morphogenesis, that may provide new insights on the etiology of schizophrenia.
Enhancing E-Business Communication with a Hybrid Rule-Based and Extractive-Based Chatbot
Authors: Dogan Onur , Gurcan Omer Faruk
Published: August 2024

E-businesses often face challenges related to customer service and communication, leading to increased dissatisfaction among customers and potential damage to the brand. To address these challenges, data-driven and AI-based approaches have emerged, including predictive analytics for optimizing customer interactions and chatbots powered by AI and NLP technologies. This study focuses on developing a hybrid rule-based and extractive-based chatbot for e-business, which can handle both routine and complex inquiries, ensuring quick and accurate responses to improve communication problems. The rule-based QA method used in the chatbot demonstrated high precision and accuracy in providing answers to user queries. The rule-based approach achieved impressive 98% accuracy and 97% precision rates among 1684 queries. The extractive-based approach received positive feedback, with 91% of users rating it as “good” or “excellent” and an average user satisfaction score of 4.38. General user satisfaction was notably high, with an average Likert score of 4.29, and 54% of participants gave the highest score of 5. Communication time was significantly improved, as the chatbot reduced average response times to 41 s, compared to the previous 20-min average for inquiries.