bluuebunny/crossref_metadata_2025 huggingface dataset:
Encouraging Adults Aged 65 and over to Participate in Resistance Training by Linking Them with a Peer: A Pilot Study
Authors: Burton Elissa , Hill Keith D. , Codde Jim , Jacques Angela , Ng Yoke Leng , Hill Anne-Marie
Published: February 2023

Resistance training (RT) is beneficial for older adults, particularly to support living independently in their home. However, fewer than 25% of older adults in Australia participate in the recommended, twice-weekly sessions. Reasons older adults do not participate in RT include not having anyone to go with or not knowing what to do. Our study linked older adults with a peer (i.e., older person already participating in RT) to help them overcome these barriers. The aim of our study was to determine whether peer support was suitable for older adults participating in RT for the first time in the home or gymnasium setting. Each group (home vs. gymnasium) received a 6 week, twice-weekly program. Twenty-one participants completed the 6 week intervention: 14 in the home group and seven in the gymnasium group. The home group completed significantly more sessions per week (2.7 vs. 1.8) than the gymnasium group. Although both groups significantly improved on many physical assessments, no between-group differences were found. However, it is suitable to link a peer for support with novice older people participating in a RT program for the first time in the home or gymnasium. It is recommended that future studies explore whether peer support improves sustainability.
Comparison and Analysis of Detection Methods for Typhoon-Storm Surges Based on Tide-Gauge Data—Taking Coasts of China as Examples
Authors: Ma Peipei , Li Guosheng
Published: February 2023

Global warming is predicted to lead to a new geographic and spatial distribution of storm-surge events and an increase in their activity intensity. Therefore, it is necessary to detect storm-surge events in order to reveal temporal and spatial variations in their activity intensity. This study attempted to detect storm-surge events from the perspective of detecting outliers. Four common outlier-detection methods, the Pauta criterion (PC), Chauvenet criterion (CC), Pareto distribution (PD) and kurtosis coefficient (KC), were used to detect the storm-surge events from the hourly residual water level data of 14 tide gauges along the coasts of China. This paper evaluates the comprehensive ability of the four methods to detect storm-surge events by combining historical typhoon-storm-surge events and deep-learning target-detection-evaluation indicators. The results indicate that (1) all of the four methods are feasible for detecting storm surge events; (2) the PC has the highest comprehensive detection ability for storm-surge events (F1 = 0.66), making it the most suitable for typhoon-storm-surge detection in coastal areas of China; the CC has the highest detection accuracy for typhoon-storm-surge events (precision = 0.89), although the recall of the CC is the lowest (recall = 0.42), as only severe storm surges were detected. This paper therefore evaluates four storm-surge-detection methods in coastal areas of China and provides a basis for the evaluation of storm-surge-detection methods and detection algorithms.
Effect of Menstrual Cycle Phase on the Recovery Process of High-Intensity Interval Exercise—A Cross-Sectional Observational Study
Authors: Benito Pedro J. , Alfaro-Magallanes Víctor M. , Rael Beatriz , Castro Eliane A. , Romero-Parra Nuria , Rojo-Tirado Miguel A. , Peinado Ana B.
Published: February 2023

Although the study of the menstrual cycle influence on endurance exercise has recently increased, there is a lack of literature studying its influence on females’ cardiorespiratory recovery. Thus, the aim of the present work was to assess menstrual cycle influence on post-exercise recovery following a high intensity interval exercise in trained females. Thirteen eumenorrheic endurance-trained females performed an interval running protocol in three menstrual cycle phases: early follicular phase (EFP), late follicular phase (LFP), and mid-luteal phase (MLP). The protocol consisted of 8 × 3-min bouts at 85% of their maximal aerobic speed (vVO2peak) with a 90-s rest between bouts and a final 5-min active recovery at 30% vVO2peak. All variables were averaged every 15 s, obtaining 19 moments during recovery (time factor). To analyze the effects of the menstrual cycle on the final active cardiorespiratory recovery, an ANOVA for repeated measures was performed. ANOVA showed an effect on menstrual cycle phase on ventilation (EFP: 1.27 ± 0.35; LFP: 1.19 ± 0.36; MLP: 1.27 ± 0.37), breathing frequency (EFP: 35.14 ± 7.14; LFP: 36.32 ± 7.11; MLP: 37.62 ± 7.23), and carbon dioxide production (EFP: 1120.46 ± 137.62; LFP: 1079.50 ± 129.57; MLP: 1148.78 ± 107.91). Regarding the interaction results (phase x time), ventilation is higher at many of the recovery times during the MLP, with less frequent differences between EFP and LFP (F = 1.586; p = 0.019), while breathing reserve is lower at many of the recovery times during MLP, with less time differences between EFP and LFP (F = 1.643; p = 0.013). It seems that the menstrual cycle affects post-exercise recovery specially during the MLP, rising ventilation and lowering breathing reserve, giving rise to an impaired ventilatory efficiency.
Ending the HIV Epidemic: Identifying Barriers and Facilitators to Implement Molecular HIV Surveillance to Develop Real-Time Cluster Detection and Response Interventions for Local Communities
Authors: Garcia Moctezuma , Devlin Samantha , Kerman Jared , Fujimoto Kayo , Hirschhorn Lisa R. , Phillips Gregory , Schneider John , McNulty Moira C.
Published: February 2023

The rapid implementation of molecular HIV surveillance (MHS) has resulted in significant challenges for local health departments to develop real-time cluster detection and response (CDR) interventions for priority populations impacted by HIV. This study is among the first to explore professionals’ strategies to implement MHS and develop CDR interventions in real-world public health settings. Methods: Semi-structured qualitative interviews were completed by 21 public health stakeholders in the United States’ southern and midwestern regions throughout 2020–2022 to identify themes related to the implementation and development of MHS and CDR. Results for the thematic analysis revealed (1) strengths and limitations in utilizing HIV surveillance data for real-time CDR; (2) limitations of MHS data due to medical provider and staff concerns related to CDR; (3) divergent perspectives on the effectiveness of partner services; (4) optimism, but reluctance about the social network strategy; and (5) enhanced partnerships with community stakeholders to address MHS-related concerns. Conclusions: Enhancing MHS and CDR efforts requires a centralized system for staff to access public health data from multiple databases to develop CDR interventions; designating staff dedicated to CDR interventions; and establishing equitable meaningful partnerships with local community stakeholders to address MHS concerns and develop culturally informed CDR interventions.
Acrylamide-Induced Changes in the Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Immunoreactivity in Small Intestinal Intramural Neurons in Pigs
Authors: Karpiesiuk Aleksandra , Całka Jarosław , Palus Katarzyna
Published: February 2023

Background: A particularly pressing problem is determining consumer-safe doses of potentially health- and life-threatening substances, such as acrylamide. The aim of the study was to determine how acrylamide affects the pituitary adenylate cyclase-activating polypeptide (PACAP)-immunoreactive intramural neurons in the small intestine of sexually immature gilts. Methods: The study was conducted on 15 sexually immature Danish gilts receiving for 28 days empty gelatin capsules or acrylamide in low (0.5 µg/kg of body weight (b.w.)/day) and high (5 µg/kg b.w./day) doses. After euthanasia, intestinal sections were stained using the double immunofluorescence staining procedure. Results: Studies have shown that oral administration of acrylamide in both doses induced a response of intramural neurons expressed as an increase in the population of PACAP-immunoreactive neurons in the small intestine. In the duodenum, only in the myenteric plexus (MP) was an increase in the number of PACAP-immunoreactive (IR) neurons observed in both experimental groups, while in the outer submucous plexus (OSP) and inner submucous plexus (ISP), an increase was noted only in the high-dose group. In the jejunum, both doses of acrylamide led to an increase in the population of PACAP-IR neurons in each enteric plexus (MP, OSP, ISP), while in the ileum, only supplementation with the higher dose of acrylamide increased the number of PACAP-IR enteric neurons in the MP, OSP, and ISP. Conclusions: The obtained results suggest the participation of PACAP in acrylamide-induced plasticity of enteric neurons, which may be an important line of defence from the harmful action of acrylamide on the small intestines.
Physical Activity in the COVID-19 Era and Its Impact on Adolescents’ Well-Being
Authors: Bozzola Elena , Barni Sarah , Ficari Andrea , Villani Alberto
Published: February 2023

Physical inactivity and sedentary habits are among the major risk factors for decreased physical and mental well-being. Since the onset of the COVID-19 pandemic, normal daily routines changed, including physical activity (PA) habits. The aim of this manuscript is to review the literature according to the PRISMA guidelines in order to analyze the changes in PA and exercise practice after the onset of the COVID-19 pandemic and its impact on the well-being of adolescents. A PubMed search was performed using the keywords “Exercise” [Mesh]) AND “COVID-19” [Mesh], and filters to limit the research to pertain to adolescents (13–18 years) and English reports. Out of the search, 15 reports met the criteria for inclusion in the study. The main findings outlined a global decrease in PA levels associated with decreased well-being levels, modified eating habits and leisure time activity, and increased obesity, anxiety, and depression among adolescents. PA is a significant health determinant and should be improved through the awareness of the benefits of regular PA and of the risks of sedentary behavior, as well as through support from family, friends, and teachers. Providing PA at school, as a part of the academic program, increasing the availability of equipment and facilities, and promoting at-home PA options are suggested as support for increasing PA in all countries and settings.
Latinx Individuals Who Smoke Daily with and without a Probable Anxiety Disorder: Differences in Smoking Behavior and Beliefs about Abstinence
Authors: Zvolensky Michael J. , Clausen Bryce K. , Shepherd Justin M. , Redmond Brooke Y. , Garey Lorra , Heggeness Luke F. , Bizier Andre , Brown Richard A. , Bogiaizian Daniel , López Salazar Patricio
Published: February 2023

There is a well-established relation between anxiety psychopathology and smoking in the general population. However, little work focuses on Latinx/Hispanic (hereafter Latinx) persons who smoke from this comorbidity perspective. The present investigation aimed to explore differences among English-speaking Latinx adults who live in the United States (US) and smoke cigarettes with and without a probable anxiety disorder in terms of cigarette dependence, perceived barriers for quitting, severity of problems when quitting, and smoking abstinence expectancies. The sample included 338 adult Latinx daily cigarette smokers (Mage = 35.53 years; SD = 8.65; age range 18–61; 37.3% female) who identified as Latinx and were recruited nationally throughout the US. Results indicated that among Latinx persons who smoke, those with a probable anxiety disorder (compared to those without) were more likely to demonstrate higher levels of cigarette dependence, severity of problems when trying to quit, perceived barriers for quitting, and negative abstinence expectancies after adjusting for key variables linked to smoking and anxiety (e.g., hazardous drinking, education). The current findings are the first to document probable anxiety disorder status as a clinically relevant factor for a wide range of smoking variables and beliefs about abstinence among Latinx persons who smoke.
Web Geographic Information System: A Support Tool for the Study, Evaluation, and Monitoring of Foci of Malaria Transmission in Mexico
Authors: Santos-Luna René , Román-Pérez Susana , Reyes-Cabrera Gerardo , Sánchez-Arcos María del Rosario , Correa-Morales Fabián , Pérez-Solano Marco Antonio
Published: February 2023

Malaria is currently an endemic disease in Mexico. The country joined the WHO’s E-25 initiative for the elimination of Plasmodium vivax to achieve elimination and certification within the established period. Having a Web-based information system was, therefore, deemed necessary to assist in the detection, investigation, and elimination of transmission in the foci, as well as for the timely treatment of malaria-positive cases. The “Information System for the Elimination of Malaria in Mexico” was designed, developed, and implemented with a geographic vision, which includes a Web tool to georeference homes and aquatic systems, a dashboard and an indicator evaluation card for monitoring activities, notification of probable cases, and vector control among other indicators. The implementation of the system was gradual in the seven states that are currently in the malaria elimination phase; subsequently, the system was implemented in non-transmission states. In 2020, the system implementation stage began; first, the basic data of more than 96,000 homes throughout the country were georeferenced, and then the primary data capture tools of 17 formats, 32 reports, and 2 geographic viewers were enabled for information queries. A total of 56 active foci have been identified in 406 localities as well as 71 residual foci in 320 localities. Recently, the Foci Manager was developed, which is a specific tool for the study, evaluation, and monitoring of active foci through a GIS, a dashboard, and a systematized evaluation certificate. Georeferencing tools decreased the cost of spatial data collection.
A Novel Low-Cost Uroflowmetry for Patient Telemonitoring
Authors: Pandolfo Savio Domenico , Crauso Federica , Aveta Achille , Cilio Simone , Barone Biagio , Napolitano Luigi , Scarpato Antonio , Mirto Benito Fabio , Serino Francesco , Del Giudice Francesco , Chung Benjamin I. , Crocerossa Fabio , Di Zazzo Erika , Trama Francesco , Vaglio Ruggero , Wu Zhenjie , Verze Paolo , Imbimbo Ciro , Crocetto Felice
Published: February 2023

Uroflowmetry (UF) is a crucial guideline-recommended tool for men with benign prostatic obstruction (BPO). Moreover, UF is a helpful decision-making tool for the management of patients with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). In the last few years, telemedicine and telehealth have increased exponentially as cost-effective treatment options for both patients and physicians. Telemedicine and telehealth have been well positioned during the COVID-19 pandemic to prevent healthcare system overload and to ensure adequate management of patients through screening, diagnosis, and follow-up at home. In the present manuscript, the main characteristics and performance of a novel and low-cost device for home-based UF have been analyzed. The simple weight-transducer method has been applied to perform UF. An inexpensive load cell connected to a 24 bit analogic digital converter (ADC) sends data to a cloud server via SIM card or home Wi-Fi. Data are processed and shown in graphics with both volume and flow rate as a function of time, allowing for measurement of average flow rate, maximum flow rate, voided volume, and voiding time. A numerical algorithm allows for filtering of the dynamic effect due to the urine gravity acceleration and for removing the funnel to simplify the home measurement procedure. Through an online platform, the physician can see and compare each UF data. The device’s reliability has been validated in a first laboratory setting and showed excellent performance. This approach based on domiciliary tests and an online platform can revolutionize the urologic clinic landscape by offering a constant patient cost-effective follow-up, eliminating the time wasted waiting in the office setting.
High VEGFR3 Expression Reduces Doxorubicin Efficacy in Triple-Negative Breast Cancer
Authors: Torres-Ruiz Sandra , Tormo Eduardo , Garrido-Cano Iris , Lameirinhas Ana , Rojo Federico , Madoz-Gúrpide Juan , Burgués Octavio , Hernando Cristina , Bermejo Begoña , Martínez María Teresa , Lluch Ana , Cejalvo Juan Miguel , Eroles Pilar
Published: February 2023

Due to the lack of specific targets, cytotoxic chemotherapy still represents the common standard treatment for triple-negative breast patients. Despite the harmful effect of chemotherapy on tumor cells, there is evidence that treatment could modulate the tumor microenvironment in a way favoring the propagation of the tumor. In addition, the lymphangiogenesis process and its factors could be involved in this counter-therapeutic event. In our study, we have evaluated the expression of the main lymphangiogenic receptor VEGFR3 in two triple-negative breast cancer in vitro models, resistant or not to doxorubicin treatment. The expression of the receptor, at mRNA and protein levels, was higher in doxorubicin-resistant cells than in parental cells. In addition, we confirmed the upregulation of VEGFR3 levels after a short treatment with doxorubicin. Furthermore, VEGFR3 silencing reduced cell proliferation and migration capacities in both cell lines. Interestingly, high VEGFR3 expression was significantly positively correlated with worse survival in patients treated with chemotherapy. Furthermore, we have found that patients with high expression of VEGFR3 present shorter relapse-free survival than patients with low levels of the receptor. In conclusion, elevated VEGFR3 levels correlate with poor survival in patients and with reduced doxorubicin treatment efficacy in vitro. Our results suggest that the levels of this receptor could be a potential marker of meager doxorubicin response. Consequently, our results suggest that the combination of chemotherapy and VEGFR3 blockage could be a potentially useful therapeutic strategy for the treatment of triple-negative breast cancer.
Osteoblasts and Fibroblasts Interaction with a Porcine Acellular Dermal Matrix Membrane
Authors: Felice Pietro , D’Amico Emira , Pierfelice Tania Vanessa , Petrini Morena , Barausse Carlo , Karaban Maryia , Barone Antonio , Iezzi Giovanna
Published: February 2023

The use of collagen membranes has remained the gold standard in GTR/GBR. In this study, the features and the biological activities of an acellular porcine dermis collagen matrix membrane applicable during dental surgery were investigated, and also by applying hydration with NaCl. Thus, two tested membranes were distinguished, the H-Membrane and Membrane, compared to the control cell culture plastic. The characterization was performed by SEM and histological analyses. In contrast, the biocompatibility was investigated on HGF and HOB cells at 3, 7, and 14 days by MTT for proliferation study; by SEM and histology for cell interaction study; and by RT-PCR for function-related genes study. In HOBs seeded on membranes, mineralization functions by ALP assay and Alizarin Red staining were also investigated. Results indicated that the tested membranes, especially when hydrated, can promote the proliferation and attachment of cells at each time. Furthermore, membranes significantly increased ALP and mineralization activities in HOBs as well as the osteoblastic-related genes ALP and OCN. Similarly, membranes significantly increased ECM-related and MMP8 gene expression in HGFs. In conclusion, the tested acellular porcine dermis collagen matrix membrane, mainly when it is hydrated, behaved as a suitable microenvironment for oral cells.
Discovery of the 3-Amino-1,2,4-triazine-Based Library as Selective PDK1 Inhibitors with Therapeutic Potential in Highly Aggressive Pancreatic Ductal Adenocarcinoma
Authors: Carbone Daniela , De Franco Michele , Pecoraro Camilla , Bassani Davide , Pavan Matteo , Cascioferro Stella , Parrino Barbara , Cirrincione Girolamo , Dall’Acqua Stefano , Moro Stefano , Gandin Valentina , Diana Patrizia
Published: February 2023

Pyruvate dehydrogenase kinases (PDKs) are serine/threonine kinases, that are directly involved in altered cancer cell metabolism, resulting in cancer aggressiveness and resistance. Dichloroacetic acid (DCA) is the first PDK inhibitor that has entered phase II clinical; however, several side effects associated with weak anticancer activity and excessive drug dose (100 mg/kg) have led to its limitation in clinical application. Building upon a molecular hybridization approach, a small library of 3-amino-1,2,4-triazine derivatives has been designed, synthesized, and characterized for their PDK inhibitory activity using in silico, in vitro, and in vivo assays. Biochemical screenings showed that all synthesized compounds are potent and subtype-selective inhibitors of PDK. Accordingly, molecular modeling studies revealed that a lot of ligands can be properly placed inside the ATP-binding site of PDK1. Interestingly, 2D and 3D cell studies revealed their ability to induce cancer cell death at low micromolar doses, being extremely effective against human pancreatic KRAS mutated cancer cells. Cellular mechanistic studies confirm their ability to hamper the PDK/PDH axis, thus leading to metabolic/redox cellular impairment, and to ultimately trigger apoptotic cancer cell death. Remarkably, preliminary in vivo studies performed on a highly aggressive and metastatic Kras-mutant solid tumor model confirm the ability of the most representative compound 5i to target the PDH/PDK axis in vivo and highlighted its equal efficacy and better tolerability profile with respect to those elicited by the reference FDA approved drugs, cisplatin and gemcitabine. Collectively, the data highlights the promising anticancer potential of these novel PDK-targeting derivatives toward obtaining clinical candidates for combatting highly aggressive KRAS-mutant pancreatic ductal adenocarcinomas.
Effects of Arbuscular Mycorrhizal Fungus on Sodium and Chloride Ion Channels of Casuarina glauca under Salt Stress
Authors: Wang Yihan , Dong Fengxin , Chen Hui , Xu Tingying , Tang Ming
Published: February 2023

Casuarina glauca is an important coastal protection forest species, which is exposed to high salt stress all year round. Arbuscular mycorrhizal fungi (AMF) can promote the growth and salt tolerance of C. glauca under salt stress. However, the effects of AMF on the distribution of Na+ and Cl− and the expression of related genes in C. glauca under salt stress need to be further explored. This study explored the effects of Rhizophagus irregularis on plant biomass, the distribution of Na+ and Cl−, and the expression of related genes in C. glauca under NaCl stress through pot simulation experiments. The results revealed that the mechanisms of Na+ and Cl− transport of C. glauca under NaCl stress were different. C. glauca took a salt accumulation approach to Na+, transferring Na+ from roots to shoots. Salt accumulation of Na+ promoted by AMF was associated with CgNHX7. The transport mechanism of C. glauca to Cl− might involve salt exclusion rather than salt accumulation, and Cl− was no longer transferred to shoots in large quantities but started to accumulate in roots. However, AMF alleviated Na+ and Cl− stress by similar mechanisms. AMF could promote salt dilution of C. glauca by increasing biomass and the content of K+, compartmentalizing Na+ and Cl− in vacuoles. These processes were associated with the expression of CgNHX1, CgNHX2-1, CgCLCD, CgCLCF, and CgCLCG. Our study will provide a theoretical basis for the application of AMF to improve salt tolerance in plants.
Polyphenols with Anti-Inflammatory Properties: Synthesis and Biological Activity of Novel Curcumin Derivatives
Authors: González Yisett , Mojica-Flores Randy , Moreno-Labrador Dilan , Cubilla-Rios Luis , Rao K. S. Jagannatha , Fernández Patricia L. , Larionov Oleg V. , Lakey-Beitia Johant
Published: February 2023

Herein, we describe the synthesis and evaluation of anti-inflammatory activities of new curcumin derivatives. The thirteen curcumin derivatives were synthesized by Steglich esterification on one or both of the phenolic rings of curcumin with the aim of providing improved anti-inflammatory activity. Monofunctionalized compounds showed better bioactivity than the difunctionalized derivatives in terms of inhibiting IL-6 production, and known compound 2 presented the highest activity. Additionally, this compound showed strong activity against PGE2. Structure–activity relationship studies were carried out for both IL-6 and PGE2, and it was found that the activity of this series of compounds increases when a free hydroxyl group or aromatic ligands are present on the curcumin ring and a linker moiety is absent. Compound 2 remained the highest activity in modulating IL-6 production and showed strong activity against PGE2 synthesis.
NF-κB Decoy ODN-Loaded Poly(Lactic-co-glycolic Acid) Nanospheres Inhibit Alveolar Ridge Resorption
Authors: Huang Albert chun-shuo , Ishida Yuji , Li Kai , Rintanalert Duantawan , Hatano-sato Kasumi , Oishi Shuji , Hosomichi Jun , Usumi-fujita Risa , Yamaguchi Hiroyuki , Tsujimoto Hiroyuki , Sasai Aiko , Ochi Ayaka , Watanabe Hajime , Ono Takashi
Published: February 2023

Residual ridge resorption combined with dimensional loss resulting from tooth extraction has a prolonged correlation with early excessive inflammation. Nuclear factor-kappa B (NF-κB) decoy oligodeoxynucleotides (ODNs) are double-stranded DNA sequences capable of downregulating the expression of downstream genes of the NF-κB pathway, which is recognized for regulating prototypical proinflammatory signals, physiological bone metabolism, pathologic bone destruction, and bone regeneration. The aim of this study was to investigate the therapeutic effect of NF-κB decoy ODNs on the extraction sockets of Wistar/ST rats when delivered by poly(lactic-co-glycolic acid) (PLGA) nanospheres. Microcomputed tomography and trabecular bone analysis following treatment with NF-κB decoy ODN-loaded PLGA nanospheres (PLGA-NfDs) demonstrated inhibition of vertical alveolar bone loss with increased bone volume, smoother trabecular bone surface, thicker trabecular bone, larger trabecular number and separation, and fewer bone porosities. Histomorphometric and reverse transcription–quantitative polymerase chain reaction analysis revealed reduced tartrate-resistant acid phosphatase-expressing osteoclasts, interleukin-1β, tumor necrosis factor-α, receptor activator of NF-κB ligand, turnover rate, and increased transforming growth factor-β1 immunopositive reactions and relative gene expression. These data demonstrate that local NF-κB decoy ODN transfection via PLGA-NfD can be used to effectively suppress inflammation in a tooth-extraction socket during the healing process, with the potential to accelerate new bone formation.
Synthesis and Characterization of Nanoparticle-Based Dexamethasone-Polypeptide Conjugates as Potential Intravitreal Delivery Systems
Authors: Zashikhina Natalia , Gladnev Sergei , Sharoyko Vladimir , Korzhikov-Vlakh Viktor , Korzhikova-Vlakh Evgenia , Tennikova Tatiana
Published: February 2023

The use of dexamethasone for eye disease treatment is limited by its low solubility, bioavailability, and rapid elimination when applied topically. The covalent conjugation of dexamethasone with polymeric carriers is a promising strategy to overcome existing drawbacks. In this work, amphiphilic polypeptides capable of self-assembly into nanoparticles were proposed as potential delivery systems for intravitreal delivery. The nanoparticles were prepared and characterized using poly(L-glutamic acid-co-D-phenylalanine) and poly(L-lysine-co-D/L-phenylalanine) as well as poly(L-lysine-co-D/L-phenylalanine) covered with heparin. The critical association concentration for the polypeptides obtained was in the 4.2–9.4 μg/mL range. The hydrodynamic size of the formed nanoparticles was between 90 and 210 nm, and they had an index of polydispersity between 0.08 and 0.27 and an absolute zeta-potential value between 20 and 45 mV. The ability of nanoparticles to migrate in the vitreous humor was examined using intact porcine vitreous. Conjugation of DEX with polypeptides was performed by additional succinylation of DEX and activation of carboxyl groups introduced to react with primary amines in polypeptides. The structures of all intermediate and final compounds were verified by 1H NMR spectroscopy. The amount of conjugated DEX can be varied from 6 to 220 µg/mg of polymer. The hydrodynamic diameter of the nanoparticle-based conjugates was increased to 200–370 nm, depending on the polymer sample and drug loading. The release of DEX from the conjugates due to hydrolysis of the ester bond between DEX and the succinyl moiety was studied both in a buffer medium and a vitreous/buffer mixture (50/50, v/v). As expected, the release in the vitreous medium was faster. However, the release rate could be controlled in the range of 96–192 h by varying the polymer composition. In addition, several mathematical models were used to assess the release profiles and figure out how DEX is released.
In Vitro Interaction of Melanoma-Derived Extracellular Vesicles with Collagen
Authors: Palmulli Roberta , Bresteau Enzo , Raposo Graça , Montagnac Guillaume , van Niel Guillaume
Published: February 2023

Extracellular vesicles are now considered as active contributors to melanoma progression through their capacity to modify the tumor microenvironment and to favor the formation of a pre-metastatic niche. These prometastatic roles of tumor-derived EVs would pass through their interaction with the extracellular matrix (ECM) and its remodeling, in turn providing a substrate favoring persistent tumor cell migration. Nevertheless, the capacity of EVs to directly interact with ECM components is still questionable. In this study, we use electron microscopy and a pull-down assay to test the capacity of sEVs, derived from different melanoma cell lines, to physically interact with collagen I. We were able to generate collagen fibrils coated with sEVs and to show that melanoma cells release subpopulations of sEVs that can differentially interact with collagen.
Therapeutic Implications of the Drug Resistance Conferred by Extracellular Vesicles Derived from Triple-Negative Breast Cancer Cells
Authors: Yi Yong Weon
Published: February 2023

Anticancer drug resistance is a significant impediment in current cancer treatment. Extracellular vesicles (EVs) derived from cancer cells were recently acknowledged as a critical mechanism of drug resistance, tumor progression, and metastasis. EVs are enveloped vesicles comprising a lipid bilayer that transfers various cargo, including proteins, nucleic acids, lipids, and metabolites, from an originating cell to a recipient cell. Investigating the mechanisms whereby EVs confer drug resistance is still in the early stages. In this review, I analyze the roles of EVs derived from triple-negative breast cancer cells (TNBC-EVs) in anticancer drug resistance and discuss strategies to overcome TNBC-EV-mediated drug resistance.
Pollen-Pistil Interaction
Authors: Cai Giampiero , Aloisi Iris , Del Duca Stefano
Published: February 2023

The aim of this Special Issue is to highlight the molecular dialogue between the pollen tube and the pistil [...]
Engineered Bone Marrow Stem Cell-Sheets Alleviate Renal Damage in a Rat Chronic Glomerulonephritis Model
Authors: Wang Bin , Kim Kyungsook , Tian Mi , Kameishi Sumako , Zhuang Lili , Okano Teruo , Huang Yufeng
Published: February 2023

Although mesenchymal stem cell (MSC)-based regenerative therapy is being developed for the treatment of kidney diseases, cell delivery and engraftment still need to be improved. Cell sheet technology has been developed as a new cell delivery method, to recover cells as a sheet form retaining intrinsic cell adhesion proteins, which promotes its transplantation efficiency to the target tissue. We thus hypothesized that MSC sheets would therapeutically reduce kidney disease with high transplantation efficiency. When the chronic glomerulonephritis was induced by two injections of the anti-Thy 1.1 antibody (OX-7) in rats, the therapeutic efficacy of rat bone marrow stem cell (rBMSC) sheet transplantation was evaluated. The rBMSC-sheets were prepared using the temperature-responsive cell-culture surfaces and transplanted as patches onto the surface of two kidneys of each rat at 24 h after the first injection of OX-7. At 4 weeks, retention of the transplanted MSC-sheets was confirmed, and the animals with MSC-sheets showed significant reductions in proteinuria, glomerular staining for extracellular matrix protein, and renal production of TGFß1, PAI-1, collagen I, and fibronectin. The treatment also ameliorated podocyte and renal tubular injury, as evidenced by a reversal in the reductions of WT-1, podocin, and nephrin and by renal overexpression of KIM-1 and NGAL. Furthermore, the treatment enhanced gene expression of regenerative factors, and IL-10, Bcl-2, and HO-1 mRNA levels, but reduced TSP-1 levels, NF-kB, and NAPDH oxidase production in the kidney. These results strongly support our hypothesis that MSC-sheets facilitated MSC transplantation and function, and effectively retarded progressive renal fibrosis via paracrine actions on anti-cellular inflammation, oxidative stress, and apoptosis and promoted regeneration.
Molecular Mechanisms of Pregnancy-Related Vascular Remodeling and Pregnancy Complications
Authors: Stevenson David K. , Wong Ronald J. , Nayak Nihar R.
Published: February 2023

The purpose of this editorial is to highlight the various observations made in this Special Issue in the International Journal of Molecular Sciences [...]
Dependence on MUC1-C in Progression of Neuroendocrine Prostate Cancer
Authors: Kufe Donald
Published: February 2023

Castration resistant prostate cancer (CRPC) is responsive to androgen receptor (AR) axis targeted agents; however, patients invariably relapse with resistant disease that often progresses to neuroendocrine prostate cancer (NEPC). Treatment-related NEPC (t-NEPC) is highly aggressive with limited therapeutic options and poor survival outcomes. The molecular basis for NEPC progression remains incompletely understood. The MUC1 gene evolved in mammals to protect barrier tissues from loss of homeostasis. MUC1 encodes the transmembrane MUC1-C subunit, which is activated by inflammation and contributes to wound repair. However, chronic activation of MUC1-C contributes to lineage plasticity and carcinogenesis. Studies in human NEPC cell models have demonstrated that MUC1-C suppresses the AR axis and induces the Yamanaka OSKM pluripotency factors. MUC1-C interacts directly with MYC and activates the expression of the BRN2 neural transcription factor (TF) and other effectors, such as ASCL1, of the NE phenotype. MUC1-C also induces the NOTCH1 stemness TF in promoting the NEPC cancer stem cell (CSC) state. These MUC1-C-driven pathways are coupled with activation of the SWI/SNF embryonic stem BAF (esBAF) and polybromo-BAF (PBAF) chromatin remodeling complexes and global changes in chromatin architecture. The effects of MUC1-C on chromatin accessibility integrate the CSC state with the control of redox balance and induction of self-renewal capacity. Importantly, targeting MUC1-C inhibits NEPC self-renewal, tumorigenicity and therapeutic resistance. This dependence on MUC1-C extends to other NE carcinomas, such as SCLC and MCC, and identify MUC1-C as a target for the treatment of these aggressive malignancies with the anti-MUC1 agents now under clinical and preclinical development.
The Immuno-Oncology and Genomic Aspects of DNA-Hypomethylating Therapeutics in Acute Myeloid Leukemia
Authors: Urabe Akiko , Chi SungGi , Minami Yosuke
Published: February 2023

Hypomethylating agents (HMAs) have been used for decades in the treatment of hematologic neoplasms, and now, have gathered attention again in terms of their combination with potent molecular-targeted agents such as a BCL-6 inhibitor venetoclax and an IDH1 inhibitor ivosidenib, as well as a novel immune-checkpoint inhibitor (anit-CD47 antibody) megrolimab. Several studies have shown that leukemic cells have a distinct immunological microenvironment, which is at least partially due to genetic alterations such as the TP53 mutation and epigenetic dysregulation. HMAs possibly improve intrinsic anti-leukemic immunity and sensitivity to immune therapies such as PD-1/PD-L1 inhibitors and anti-CD47 agents. This review describes the immuno-oncological backgrounds of the leukemic microenvironment and the therapeutic mechanisms of HMAs, as well as current clinical trials of HMAs and/or venetoclax-based combination therapies.
Transthyretin Is Commonly Upregulated in the Hippocampus of Two Stress-Induced Depression Mouse Models
Authors: Saito-Takatsuji Hidehito , Yoshitomi Yasuo , Yamamoto Ryo , Furuyama Takafumi , Ishigaki Yasuhito , Kato Nobuo , Yonekura Hideto , Ikeda Takayuki
Published: February 2023

Chronic stress can affect gene expression in the hippocampus, which alters neural and cerebrovascular functions, thereby contributing to the development of mental disorders such as depression. Although several differentially expressed genes in the depressed brain have been reported, gene expression changes in the stressed brain remain underexplored. Therefore, this study examines hippocampal gene expression in two mouse models of depression induced by forced swim stress (FSS) and repeated social defeat stress (R-SDS). Transthyretin (Ttr) was commonly upregulated in the hippocampus of both mouse models, as determined by microarray, RT-qPCR, and Western blot analyses. Evaluation of the effects of overexpressed Ttr in the hippocampus using adeno-associated virus-mediated gene transfer revealed that TTR overexpression induced depression-like behavior and upregulation of Lcn2 and several proinflammatory genes (Icam1 and Vcam1) in the hippocampus. Upregulation of these inflammation-related genes was confirmed in the hippocampus obtained from mice vulnerable to R-SDS. These results suggest that chronic stress upregulates Ttr expression in the hippocampus and that Ttr upregulation may be involved in the induction of depression-like behavior.
Amyloid Fibrils of Stefin B Show Anisotropic Properties
Authors: Žganec Matjaž , Taler Verčič Ajda , Muševič Igor , Škarabot Miha , Žerovnik Eva
Published: February 2023

Human stefin B, a member of the cystatin family of cysteine protease inhibitors, tends to form amyloid fibrils under relatively mild conditions, which is why it is used as a model protein to study amyloid fibrillation. Here, we show for the first time that bundles of amyloid fibrils, i.e., helically twisted ribbons, formed by human stefin B exhibit birefringence. This physical property is commonly observed in amyloid fibrils when stained with Congo red. However, we show that the fibrils arrange in regular anisotropic arrays and no staining is required. They share this property with anisotropic protein crystals, structured protein arrays such as tubulin and myosin, and other anisotropic elongated materials, such as textile fibres and liquid crystals. In certain macroscopic arrangements of amyloid fibrils, not only birefringence is observed, but also enhanced emission of intrinsic fluorescence, implying a possibility to detect amyloid fibrils with no labels by using optical microscopy. In our case, no enhancement of intrinsic tyrosine fluorescence was observed at 303 nm; instead, an additional fluorescence emission peak appeared at 425 to 430 nm. We believe that both phenomena, birefringence and fluorescence emission in the deep blue, should be further explored with this and other amyloidogenic proteins. This may allow the development of label-free detection methods for amyloid fibrils of different origins.
How a Rubric Score Application Empowers Teachers’ Attitudes over Computational Thinking Leverage
Authors: Dimos Ioannis , Velaora Chrysoula , Louvaris Konstantinos , Kakarountas Athanasios , Antonarakou Assimina
Published: February 2023

Computational Thinking (CT) has emerged as an umbrella term that refers to a broad set of problem-solving skills. New generations must conquer these skills in order to thrive in a computer-based world. Teachers, as agents of change, must also be familiar, trained and well-prepared in order to train children in CT. This paper examines STEM (Science, Technology, Engineering and Mathematics) and non-STEM teachers’ attitudes and readiness to adopt and utilize Computational Thinking concepts in the curriculum. The research was conducted through a descriptive assessment of students using thematically related criteria (rubrics) and a criterion on Computational Thinking usage and utilization. Fifteen teachers (n = 15) were invited to a focus group discussion in which they were asked to complete a questionnaire and, subsequently, to openly analyze their answers. The results show that the majority of teachers used computational thinking as an assessment criterion and stated that they did not face any significant problems with it. At the end of the focus group questions, they concluded that they consider participation in a training program regarding the concept and principles of computational thinking and the way they could integrate into the educational process necessary. Teachers expressed their confidence in using a set of criteria (rubric) to make students’ assessments more effective and stated that they can easily use at least one criterion for Computational Thinking.
The Fluoride Ion Release from Ion-Releasing Dental Materials after Surface Loading by Topical Treatment with Sodium Fluoride Gel
Authors: Kelić Marija , Kilić Domagoj , Kelić Katarina , Šutej Ivana , Par Matej , Peroš Kristina , Tarle Zrinka
Published: February 2023

The study aimed to investigate the rechargeability of ion-releasing dental material specimens immersed in distilled water for 25 months, which depleted their ion-releasing ability. Four restorative dental materials (alkasite composite, giomer, glass-ionomer, and composite material) presented with 24 specimens were studied after topical treatment with a concentrated fluoride gel. The effect of resin coating on the ion uptake and release was investigated on additional 42 specimens of restorative dental materials with coatings. The composite materials were coated with two adhesive systems, whereas the glass-ionomer was coated with the special coating resin. After topical fluoride exposure, ion release and specimen mass were measured at 1, 2, 3, 4, 5, 6, 7, and 14-day intervals using an ion-selective electrode and an analytical balance, respectively. The cumulative fluoride levels for the uncoated specimens of alkasite composite were significantly higher than those of giomer and glass-ionomer cement, with no statistically significant difference between the latter two materials. The conventional composite had the lowest cumulative concentration of fluoride ions (p < 0.05). The adhesive systems affected the fluoride recharge and reduced the ion concentrations absorbed by the specimens. Specimens coated with universal adhesive showed significantly higher ion release compared to universal fluoride-releasing adhesive or special coating resin for glass-ionomers (p < 0.05). No statistically significant change in specimen mass was observed during the 14-day period. Surface coating with adhesive systems as well as special coating resin for glass-ionomers affects the fluoride recharge process.
Global Trends and Future Research Directions for Temporomandibular Disorders and Stem Cells
Authors: da Silva Zuleni Alexandre , Melo Wallacy Watson Pereira , Ferreira Hadassa Helez Neves , Lima Rafael Rodrigues , Souza-Rodrigues Renata Duarte
Published: February 2023

Temporomandibular disorder (TMD) is an umbrella term used to describe various conditions that affect temporomandibular joints, masticatory muscles, and associated structures. Although the most conservative and least invasive treatment is preferable, more invasive therapies should be employed to refractory patients. Tissue engineering has been presented as a promising therapy. Our study aimed to investigate trends and point out future research directions on TMD and stem cells. A comprehensive search was carried out in the Web of Science Core Collection (WoS-CC) in October 2022. The bibliometric parameters were analyzed through descriptive statistics and graphical mapping. Thus, 125 papers, published between 1992 and 2022 in 65 journals, were selected. The period with the highest number of publications and citations was between 2012 and 2022. China has produced the most publications on the subject. The most frequently used keywords were “cartilage”, “temporomandibular joint”, “mesenchymal stem cells”, and “osteoarthritis”. Moreover, the primary type of study was in vivo. It was noticed that using stem cells to improve temporomandibular joint repair and regeneration is a significant subject of investigation. Nonetheless, a greater understanding of the biological interaction and the benefits of using these cells in patients with TMD is required.
Influence of the Compliance of a Technological System on the Machining Accuracy of Low-Stiffness Shafts in the Grinding Process
Authors: Świć Antoni , Gola Arkadiusz
Published: February 2023

This paper reports the results of research on the influence of the compliance of the technological system used in grinding low-stiffness shafts on the shape accuracy of the workpieces. The level of accuracy achieved using passive compliance compensation was assessed, and technological assumptions were formulated to further increase the shape accuracy of the low-stiffness shafts obtained in the grinding process. Taking into account the limitations of passive compliance compensation, a method for the active compensation of the compliance of the elastic technological system during the machining process was developed. The experiments showed that the accuracy of grinding was most effectively increased by adjusting the compliance and controlling the bending moments, depending on the position of the cutting force (grinding wheel) along the part. The experimental results were largely consistent with the results of the theoretical study and confirmed the assumptions made. Adjusting the compliance in the proposed way allows for the significant improvement in the accuracy and productivity of machining of low-stiffness shafts.
Design and Development of Tantalum and Strontium Ion Doped Hydroxyapatite Composite Coating on Titanium Substrate: Structural and Human Osteoblast-like Cell Viability Studies
Authors: Dommeti Vamsi Krishna , Roy Sandipan , Pramanik Sumit , Merdji Ali , Ouldyerou Abdelhak , Özcan Mutlu
Published: February 2023

In order to reduce the loosening of dental implants, surface modification with hydroxyapatite (HA) coating has shown promising results. Therefore, in this present study, the sol-gel technique has been employed to form a tantalum and strontium ion-doped hybrid HA layer coating onto the titanium (Ti)-alloy substrate. In this study, the surface modification was completed by using 3% tantalum pent oxide (Ta2O5), 3% strontium (Sr), and a combination of 1.5% Ta2O5 and 1.5% Sr as additives, along with HA gel by spin coating technique. These additives played a prominent role in producing a porous structure layer coating and further cell growth. The MG63 cell culture assay results indicated that due to the incorporation of strontium ions along with tantalum embedded in HA, cell proliferation increased significantly after a 48 h study. Therefore, the present results, including microstructure, crystal structure, binding energy, and cell proliferation, showed that the additives 1.5% Ta2O5 and 1.5% Sr embedded in HA on the Ti–substrate had an optimized porous coating structure, which will enhance bone in-growth in surface-modified Ti-implants. This material had a proper porous morphology with a roughness profile, which may be suitable for tissue in-growth between a surface-modified textured implant and bone interface and could be applicable for dental implants.