bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient Engagement Using Telemedicine in Primary Care during COVID-19 Pandemic: A Trial Study
Authors: Vicente María Asunción , Fernández César , Guilabert Mercedes , Carrillo Irene , Martín-Delgado Jimmy , Mira José Joaquín ,   Prometeo173 Working Group
Published: November 2022

The correct treatment of most non-transmissible diseases requires, in addition to adequate medication, adherence to physical activity and diet guidelines, as well as health data monitoring and patient motivation. The restrictions caused by the COVID-19 pandemic made telemedicine tools and mobile apps the best choice for monitoring patient compliance. The objective of this study was to analyze the benefits of an m-Health solution designed specifically for chronic patients during the COVID-19 pandemic. A pragmatic clinical trial with pre–post measurements of a single group was carried out with 70 patients (aged 40+) with one or more chronic conditions. Patients were provided with an ad hoc mobile app and health data measuring devices according to their diseases. The health status of the patients was monitored remotely by health professionals who could also modify the patient’s objectives according to their evolution. The results obtained show an average fulfillment of objectives of 77%. Higher fulfillment values: medication adherence (98%) and oxygen saturation (82%); lower fulfillment values: weight (48%), glucose (57%), and distance walked (57%). Globally, the ad hoc app was rated 8.72 points out of 10 (standard deviation 1.10). Concerning the pre–post analysis, there were significant improvements vs. prior apps used by the participants in the following items: improved physical activation and better control of blood pressure, diet, weight, glucose, and oxygen saturation. In conclusion, the telemedicine tool developed was useful in increasing patient engagement and adherence to treatment.
The Relationships between Prospection, Self-Efficacy, and Depression in College Students with Cross-Lagged Analysis
Authors: Yang Zhuo-Ya , Wang Ya-Ting , Xia Lei , Zheng Ying-Can , Feng Zheng-Zhi
Published: November 2022

Depression is one of the most prevalent and disabling mental health problems in college students. Previous studies have established cross-sectional associations between negative bias in prospection e.g., increased negativity in future simulation, low self-efficacy, and depressive symptoms. Nevertheless, the temporal bidirectional associations between them are rarely examined. In the current study, we collected valid data on 276 college students at two time points within a 10 week interval. Cross-lagged panel analysis was applied to investigate the relationships between proportions of negative future events, levels of self-efficacy, and depressive symptoms. Results suggested depressive symptoms predict subsequent proportions of negative prospections and levels of self-efficacy. Inversely, neither prospection nor self-efficacy predicted depression. Temporal correlations between prospection and self-efficacy were also not significant. Since this is one of the first studies that attempts to figure out temporal links between these mutually informing factors, more longitudinal research is needed to draw a firm conclusion. This study provides new insights into the relationship between negative biases in cognitions and depressive symptoms and highlights the need to intervene early with depressive symptoms before any possible cognitive distortions in college students.
Factors Associated with Knowledge of Evacuation Routes and Having an Emergency Backpack in Individuals Affected by a Major Earthquake in Piura, Peru
Authors: Valladares-Garrido Mario J. , Zapata-Castro Luis E. , Valdiviezo-Morales Christopher G. , García-Vicente Abigaíl , León-Figueroa Darwin A. , Calle-Preciado Raúl , Failoc-Rojas Virgilio E. , Pereira-Victorio César Johan , Díaz-Vélez Cristian
Published: November 2022

Information on the prevention of earthquakes in Peru, a high-risk country, is still emerging. We determined the frequency and factors associated with knowledge of evacuation routes and the use of emergency backpacks in people affected by a major earthquake. A cross-sectional study using secondary data was conducted from August–December 2021 on people that experienced the 6.1 magnitude earthquake that occurred in Piura, Peru on 30 July 2021. The outcome was self-reported knowledge of evacuation routes and the use of emergency backpacks. The association with self-reported earthquake preparation training, use of sources of information on earthquakes, and sociodemographic variables was investigated. A total of 69.5% of participants knew evacuation routes, and 46.3% had an emergency backpack. A higher frequency of knowledge of evacuation routes was associated with previous training (PR: 1.47; 95% CI: 1.15–1.87), use of the media (PR: 1.35; 95% CI: 1.06–1.72), having received information from the COEN (PR: 1.19; 95% CI: 1.02–1.40), and with a greater number of household members (PR: 1.03; 95% CI: 1.01–1.06). There is a high frequency of knowledge of evacuation routes among participants. However, basic notions of prevention culture are still needed. This research contributes to policy development on earthquake preparation at the community level.
Variation in Sediment Available-Phosphorus in Dianchi Lake and Its Impacts on Algal Growth
Authors: Chen Yongchuan , Chen Qiao , Zhang Degang , Tang Li
Published: November 2022

Sediment phosphorus (P) is an active component of the P cycle in lakes and its availability and movement could play an important role in eutrophication. Sediments from different depths in five representative sites of Dianchi Lake China, i.e., Haigeng, Dounan, Luojiacun, Xinjie, and Kunyang, were studied from January to December to evaluate the spatial and temporal dynamics in available-P and soluble-P and their impacts on algal growth. The results showed that the average sediment available-P and soluble-P were 41.2 mg kg−1 and 0.27 mg kg−1, respectively. Sediment available-P and soluble-P concentrations varied significantly among seasons, sites, and layers, with the following order: surface (0–5 cm) > middle (5–10 cm) > bottom (10–20 cm). The release and transformation characteristics of available-P and soluble-P at the sediment–water interface varied among sites. The Haigeng site, with the most severe algae blooms, had significantly higher average available-P and soluble-P in sediment than other sites. This indicated that phosphorus release and availability were associated with algal growth, and that the sediment surface (0–5 cm) is an important internal source that supports algal growth in Dianchi Lake.
Hemolytic Activity, Cytotoxicity, and Antimicrobial Effects of Silver Nanoparticles Conjugated with Lincomycin or Cefazolin
Authors: Korolev Dmitriy , Shumilo Michael , Shulmeyster Galina , Krutikov Alexander , Golovkin Alexey , Mishanin Alexander , Spiridonova Anna , Kulagina Olga , Galagudza Michael
Published: November 2022

The overuse of antibiotics has led to the emergence of resistant bacteria. A good alternative is silver nanoparticles, which have antibacterial activity against Gram-negative and Gram-positive bacteria, including multidrug-resistant strains. Their combination with already known antibiotics has a synergistic effect. In this work, we studied the synthesis of conjugates of silver nanoparticles with two antibiotics, lincomycin and cefazolin. Albumin and glutathione were used as spacer shells with functional groups. The physicochemical properties of the obtained conjugates, their cytotoxicity and synergism of antimicrobial activity were studied. The 50% antimicrobial activity of the obtained samples was shown, which allows them to be recommended for use as topical drug preparations.
Clinical Implications and Molecular Characterization of Drebrin-Positive, Tumor-Infiltrating Exhausted T Cells in Lung Cancer
Authors: Imamura Kosuke , Tomita Yusuke , Sato Ryo , Ikeda Tokunori , Iyama Shinji , Jodai Takayuki , Takahashi Misako , Takaki Akira , Akaike Kimitaka , Hamada Shohei , Sakata Shinya , Saruwatari Koichi , Saeki Sho , Ikeda Koei , Suzuki Makoto , Sakagami Takuro
Published: November 2022

T cells express an actin-binding protein, drebrin, which is recruited to the contact site between the T cells and antigen-presenting cells during the formation of immunological synapses. However, little is known about the clinical implications of drebrin-expressing, tumor-infiltrating lymphocytes (TILs). To address this issue, we evaluated 34 surgical specimens of pathological stage I–IIIA squamous cell lung cancer. The immune context of primary tumors was investigated using fluorescent multiplex immunohistochemistry. The high-speed scanning of whole-slide images was performed, and the tissue localization of TILs in the tumor cell nest and surrounding stroma was automatically profiled and quantified. Drebrin-expressing T cells were characterized using drebrin+ T cells induced in vitro and publicly available single-cell RNA sequence (scRNA-seq) database. Survival analysis using the propensity scores revealed that a high infiltration of drebrin+ TILs within the tumor cell nest was independently associated with short relapse-free survival and overall survival. Drebrin+ T cells induced in vitro co-expressed multiple exhaustion-associated molecules. The scRNA-seq analyses confirmed that the exhausted tumor-infiltrating CD8+ T cells specifically expressed drebrin. Our study suggests that drebrin-expressing T cells present an exhausted phenotype and that tumor-infiltrating drebrin+ T cells affect clinical outcomes in patients with resectable squamous cell lung cancer.
Delivery of Theranostic Nanoparticles to Various Cancers by Means of Integrin-Binding Peptides
Authors: Egorova Elena A. , Nikitin Maxim P.
Published: November 2022

Active targeting of tumors is believed to be the key to efficient cancer therapy and accurate, early-stage diagnostics. Active targeting implies minimized off-targeting and associated cytotoxicity towards healthy tissue. One way to acquire active targeting is to employ conjugates of therapeutic agents with ligands known to bind receptors overexpressed onto cancer cells. The integrin receptor family has been studied as a target for cancer treatment for almost fifty years. However, systematic knowledge on their effects on cancer cells, is yet lacking, especially when utilized as an active targeting ligand for particulate formulations. Decoration with various integrin-targeting peptides has been reported to increase nanoparticle accumulation in tumors ≥ 3-fold when compared to passively targeted delivery. In recent years, many newly discovered or rationally designed integrin-binding peptides with excellent specificity towards a single integrin receptor have emerged. Here, we show a comprehensive analysis of previously unreviewed integrin-binding peptides, provide diverse modification routes for nanoparticle conjugation, and showcase the most notable examples of their use for tumor and metastases visualization and eradication to date, as well as possibilities for combined cancer therapies for a synergetic effect. This review aims to highlight the latest advancements in integrin-binding peptide development and is directed to aid transition to the development of novel nanoparticle-based theranostic agents for cancer therapy.
Genetic Diversity Analysis Reveals Potential of the Green Peach Aphid (Myzus persicae) Resistance in Ethiopian Mustard
Authors: Zhou Fangyuan , Chen Chaoquan , Kong Lijun , Liu Shenglanjia , Zhao Kun , Zhang Yi , Zhao Tong , Liu Kaiwen , Yu Xiaolin
Published: November 2022

Brassica carinata (BBCC, 2n = 34) is commonly known as Ethiopian mustard, Abyssinian mustard, or carinata. Its excellent agronomic traits, including resistance to biotic and abiotic stresses, make it a potential genetic donor for interspecific hybridization. Myzus persicae (green peach aphid, GPA) is one of the most harmful pests of Brassica crops, significantly effecting the yield and quality. However, few aphid-resistant Brassica crop germplasms have been utilized in breeding practices, while the underlying biochemical basis of aphid resistance still remains poorly understood. In this study, we examined the genetic diversity of 75 B. carinata accessions and some plant characteristics that potentially contribute to GPA resistance. Initially, the morphological characterization showed abundant diversity in the phenotypic traits, with the dendrogram indicating that the genetic variation of the 75 accessions ranged from 0.66 to 0.98. A population structure analysis revealed that these accessions could be grouped into two main subpopulations and one admixed group, with the majority of accessions (86.67%) clustering in one subpopulation. Subsequently, there were three GPA-resistant B. carinata accessions, BC13, BC47, and BC51. The electrical penetration graph (EPG) assay detected resistance factors in the leaf mesophyll tissue and xylem. The result demonstrated that the Ethiopian mustard accessions were susceptible when the phloem probing time, the first probe time, and the G-wave time were 20.51–32.51 min, 26.36–55.54 s, and 36.18–47.84 min, respectively. In contrast, resistance of the Ethiopian mustard accessions was observed with the phloem probing time, the first probe time, and G-wave time of 41.18–70.78 min, 181.07–365.85 s, and 18.03–26.37 min, respectively. In addition, the epidermal characters, leaf anatomical structure, glucosinolate composition, defense-related enzyme activities, and callose deposition were compared between the resistant and susceptible accessions. GPA-resistant accessions had denser longitudinal leaf structure, higher wax content on the leaf surface, higher indole glucosinolate level, increased polyphenol oxidase (PPO) activity, and faster callose deposition than the susceptible accessions. This study validates that inherent physical and chemical barriers are evidently crucial factors in the resistance against GPA infestation. This study not only provide new insights into the biochemical basis of GPA resistance but also highlights the GPA-resistant B. carinata germplasm resources for the future accurate genetic improvement of Brassica crops.
Cell Metabolomics Reveals the Potential Mechanism of Aloe Emodin and Emodin Inhibiting Breast Cancer Metastasis
Authors: Cheng Guorong , Liu Zhiqiang , Zheng Zhong , Song Fengrui , Zhuang Xiaoyu , Liu Shu
Published: November 2022

Metastasis is one of the main obstacles for the treatment and prognosis of breast cancer. In this study, the effects and possible mechanisms of aloe emodin (AE) and emodin (EMD) for inhibiting breast cancer metastasis were investigated via cell metabolomics. First, a co-culture model of MCF-7 and HUVEC cells was established and compared with a traditional single culture of MCF-7 cells. The results showed that HUVEC cells could promote the development of cancer cells to a malignant phenotype. Moreover, AE and EMD could inhibit adhesion, invasion, and angiogenesis and induce anoikis of MCF-7 cells in co-culture model. Then, the potential mechanisms behind AE and EMD inhibition of MCF-7 cell metastasis were explored using a metabolomics method based on UPLC-Q-TOF/MS multivariate statistical analysis. Consequently, 27 and 13 biomarkers were identified in AE and EMD groups, respectively, including polyamine metabolism, methionine cycle, TCA cycle, glutathione metabolism, purine metabolism, and aspartate synthesis. The typical metabolites were quantitatively analyzed, and the results showed that the inhibitory effect of AE was significantly better than EMD. All results confirmed that AE and EMD could inhibit metastasis of breast cancer cells through different pathways. Our study provides an overall view of the underlying mechanisms of AE and EMD against breast cancer metastasis.
Size Effect in Hybrid TiO2:Au Nanostars for Photocatalytic Water Remediation Applications
Authors: Zheng Fangyuan , Martins Pedro M. , Queirós Joana M. , Tavares Carlos J. , Vilas-Vilela José Luis , Lanceros-Méndez Senentxu , Reguera Javier
Published: November 2022

TiO2:Au-based photocatalysis represents a promising alternative to remove contaminants of emerging concern (CECs) from wastewater under sunlight irradiation. However, spherical Au nanoparticles, generally used to sensitize TiO2, still limit the photocatalytic spectral band to the 520 nm region, neglecting a high part of sun radiation. Here, a ligand-free synthesis of TiO2:Au nanostars is reported, substantially expanding the light absorption spectral region. TiO2:Au nanostars with different Au component sizes and branching were generated and tested in the degradation of the antibiotic ciprofloxacin. Interestingly, nanoparticles with the smallest branching showed the highest photocatalytic degradation, 83% and 89% under UV and visible radiation, together with a threshold in photocatalytic activity in the red region. The applicability of these multicomponent nanoparticles was further explored with their incorporation into a porous matrix based on PVDF-HFP to open the way for a reusable energy cost-effective system in the photodegradation of polluted waters containing CECs.
Circulating Inflammatory Biomarkers in Early Prediction of Stroke-Associated Infections
Authors: Hasse Isabel M. C. , Grosse Gerrit M. , Schuppner Ramona , Van Gemmeren Till , Gabriel Maria M. , Weissenborn Karin , Lichtinghagen Ralf , Worthmann Hans
Published: November 2022

(1) Background: Patients with acute ischaemic stroke (AIS) are at high risk for stroke-associated infections (SAIs). We hypothesised that increased concentrations of systemic inflammation markers predict SAIs and unfavourable outcomes; (2) Methods: In 223 patients with AIS, blood samples were taken at ≤24 h, 3 d and 7d after a stroke, to determine IL-6, IL-10, CRP and LBP. The outcome was assessed using the modified Rankin Scale at 90 d. Patients were thoroughly examined regarding the development of SAIs; (3) Results: 47 patients developed SAIs, including 15 lower respiratory tract infections (LRTIs). IL-6 and LBP at 24 h differed, between patients with and without SAIs (IL-6: p < 0.001; LBP: p = 0.042). However, these associations could not be confirmed after adjustment for age, white blood cell count, reduced consciousness and NIHSS. When considering the subgroup of LRTIs, in patients who presented early (≤12 h after stroke, n = 139), IL-6 was independently associated with LRTIs (OR: 1.073, 95% CI: 1.002–1.148). The ROC-analysis for prediction of LRTIs showed an AUC of 0.918 for the combination of IL-6 and clinical factors; (4) Conclusions: Blood biomarkers were not predictive for total SAIs. At early stages, IL-6 was independently associated with outcome-relevant LRTIs. Further studies need to clarify the use of biochemical markers to identify patients prone to SAIs.
GADD34 Ablation Exacerbates Retinal Degeneration in P23H RHO Mice
Authors: Saltykova Irina V. , Zhylkibayev Assylbek , Gorbatyuk Oleg S. , Gorbatyuk Marina S.
Published: November 2022

The UPR is sustainably activated in degenerating retinas, leading to translational inhibition via p-eIF2α. Recent findings have demonstrated that ablation of growth arrest and DNA damage-inducible protein 34 (GADD34), a protein phosphatase 1 regulatory subunit permitting translational machinery operation through p-eIF2α elevation, does not impact the rate of translation in fast-degenerating rd16 mice. The current study aimed to validate whether P23H RHO mice degenerating at a slower pace manifest translational attenuation and whether GADD34 ablation impacts the rate of retinal degeneration via further suppression of retinal protein synthesis and apoptotic cell death. For this study, mice were examined with ERG and histological analyses. The molecular assessment was conducted in the naïve and LPS-challenged mice using Western blot and qRT-PCR analyses. Thus, this study demonstrates that the P23H RHO retinas manifest translational attenuation. However, GADD34 ablation resulted in a more prominent p-eIF2a increase without impacting the translation rate. GADD34 deficiency also led to a reduction in scotopic ERG amplitudes and an increased number of TUNEL-positive cells. Molecular analysis revealed that GADD34 deficiency reduces the expression of p-STAT3 and Il-6 while increasing the expression of Tnfa. Overall, the data indicate that GADD34 plays a multifunctional role. Under chronic UPR activation, GADD34 acts as a feedback player, dephosphorylating p-eIF2a, although this role does not seem to be critical. Additionally, GADD34 controls cytokine expression and STAT3 activation. Perhaps these molecular events are particularly important in controlling the pace of retinal degeneration.
Influence of the Microbiome Metagenomics and Epigenomics on Gastric Cancer
Authors: Mathebela Precious , Damane Botle Precious , Mulaudzi Thanyani Victor , Mkhize-Khwitshana Zilungile Lynette , Gaudji Guy Roger , Dlamini Zodwa
Published: November 2022

Gastric cancer (GC) is one of the major causes of cancer deaths worldwide. The disease is seldomly detected early and this limits treatment options. Because of its heterogeneous and complex nature, the disease remains poorly understood. The literature supports the contribution of the gut microbiome in the carcinogenesis and chemoresistance of GC. Drug resistance is the major challenge in GC therapy, occurring as a result of rewired metabolism. Metabolic rewiring stems from recurring genetic and epigenetic factors affecting cell development. The gut microbiome consists of pathogens such as H. pylori, which can foster both epigenetic alterations and mutagenesis on the host genome. Most of the bacteria implicated in GC development are Gram-negative, which makes it challenging to eradicate the disease. Gram-negative bacterium co-infections with viruses such as EBV are known as risk factors for GC. In this review, we discuss the role of microbiome-induced GC carcinogenesis. The disease risk factors associated with the presence of microorganisms and microbial dysbiosis are also discussed. In doing so, we aim to emphasize the critical role of the microbiome on cancer pathological phenotypes, and how microbiomics could serve as a potential breakthrough in determining effective GC therapeutic targets. Additionally, consideration of microbial dysbiosis in the GC classification system might aid in diagnosis and treatment decision-making, taking the specific pathogen/s involved into account.
Pathological 25 kDa C-Terminal Fragments of TDP-43 Are Present in Lymphoblastoid Cell Lines and Extracellular Vesicles from Patients Affected by Frontotemporal Lobar Degeneration and Neuronal Ceroidolipofuscinosis Carrying a GRN Mutation
Authors: Cimini Sara , Bellini Sonia , Saraceno Claudia , Benussi Luisa , Ghidoni Roberta , Giliani Silvia Clara , Puoti Gianfranco , Canafoglia Laura , Giaccone Giorgio , Rossi Giacomina
Published: November 2022

Frontotemporal lobar degeneration (FTLD) is a complex disease, characterized by progressive degeneration of frontal and temporal lobes. Mutations in progranulin (GRN) gene have been found in up to 50% of patients with familial FTLD. Abnormal deposits of post-translationally-modified TAR DNA-binding protein of 43 kDa (TDP-43) represent one of the main hallmarks of the brain pathology. To investigate in peripheral cells the presence of the different TDP-43 forms, especially the toxic 25 kDa fragments, we analyzed lymphoblastoid cell lines (LCLs) and the derived extracellular vesicles (EVs) from patients carrying a GRN mutation, together with wild-type (WT) healthy controls. After characterizing EV sizes and concentrations by nanoparticle tracking analysis, we investigated the levels of different forms of the TDP-43 protein in LCLs and respective EVs by Western blot. Our results showed a trend of concentration decreasing in EVs derived from GRN-mutated LCLs, although not reaching statistical significance. A general increase in p-TDP-43 levels in GRN-mutated LCLs and EVs was observed. In particular, the toxic 25 kDa fragments of p-TDP-43 were only present in GRN-mutated LCLs and were absent in the WT controls. Furthermore, these fragments appeared to be more concentrated in EVs than in LCLs, suggesting a relevant role of EVs in spreading pathological molecules between cells.
Involvement of the p38 MAPK-NLRC4-Caspase-1 Pathway in Ionizing Radiation-Enhanced Macrophage IL-1β Production
Authors: Baik Ji Sue , Seo You Na , Lee Young-Choon , Yi Joo Mi , Rhee Man Hee , Park Moon-Taek , Kim Sung Dae
Published: November 2022

Macrophages are abundant immune cells in the tumor microenvironment and are crucial in regulating tumor malignancy. We previously reported that ionizing radiation (IR) increases the production of interleukin (IL)-1β in lipopolysaccharide (LPS)-treated macrophages, contributing to the malignancy of colorectal cancer cells; however, the mechanism remained unclear. Here, we show that IR increases the activity of cysteine-aspartate-specific protease 1 (caspase-1), which is regulated by the inflammasome, and cleaves premature IL-1β to mature IL-1β in RAW264.7 macrophages. Irradiated RAW264.7 cells showed increased expression of NLRC4 inflammasome, which controls the activity of caspase-1 and IL-1β production. Silencing of NLRC4 using RNA interference inhibited the IR-induced increase in IL-1β production. Activation of the inflammasome can be regulated by mitogen-activated protein kinase (MAPK)s in macrophages. In RAW264.7 cells, IR increased the phosphorylation of p38 MAPK but not extracellular signal-regulated kinase and c-Jun N-terminal kinase. Moreover, a selective inhibitor of p38 MAPK inhibited LPS-induced IL-1β production and NLRC4 inflammasome expression in irradiated RAW264.7 macrophages. Our results indicate that IR-induced activation of the p38 MAPK-NLRC4-caspase-1 activation pathway in macrophages increases IL-1β production in response to LPS.
Acute Effects of Ocrelizumab Infusion in Multiple Sclerosis Patients
Authors: Akgün Katja , Behrens Johanna , Schriefer Dirk , Ziemssen Tjalf
Published: November 2022

B cell-depleting therapies such as ocrelizumab (OCR) are highly effective in people with multiple sclerosis (MS). Especially at treatment start and initial infusion, infusion-related reactions (IRR) are a common adverse event. The relevance of acute changes of cell-depleting therapies on peripheral immune compartments and routine lab testing is important for clinical practice. We systematically analyzed routine blood parameters, detailed blood immunophenotyping and serum cytokine profiles in 45 MS patients starting on OCR. Blood samples were collected before and after corticosteroid premedication and directly after each OCR infusion of the first three ocrelizumab infusions. Blood B cells were rapidly depleted and accompanied only by a mild cytokine release at the first OCR infusion. Cytokine release was not significantly detectable from a third application in line with decreasing IRRs. B cell depletion was accompanied by short-lived changes in other immune cell populations in number, activation and cytokine secretion after each OCR infusion. Standard lab parameters did not show any clinically relevant changes. Our data demonstrate only mild changes during the first OCR infusion, which are not present any more during long-term treatment.
Electrospun Azithromycin-Laden Gelatin Methacryloyl Fibers for Endodontic Infection Control
Authors: Ayoub Afzan A. , Mahmoud Abdel H. , Ribeiro Juliana S. , Daghrery Arwa , Xu Jinping , Fenno J. Christopher , Schwendeman Anna , Sasaki Hajime , Dal-Fabbro Renan , Bottino Marco C.
Published: November 2022

This study was aimed at engineering photocrosslinkable azithromycin (AZ)-laden gelatin methacryloyl fibers via electrospinning to serve as a localized and biodegradable drug delivery system for endodontic infection control. AZ at three distinct amounts was mixed with solubilized gelatin methacryloyl and the photoinitiator to obtain the following fibers: GelMA+5%AZ, GelMA+10%AZ, and GelMA+15%AZ. Fiber morphology, diameter, AZ incorporation, mechanical properties, degradation profile, and antimicrobial action against Aggregatibacter actinomycetemcomitans and Actinomyces naeslundii were also studied. In vitro compatibility with human-derived dental pulp stem cells and inflammatory response in vivo using a subcutaneous rat model were also determined. A bead-free fibrous microstructure with interconnected pores was observed for all groups. GelMA and GelMA+10%AZ had the highest fiber diameter means. The tensile strength of the GelMA-based fibers was reduced upon AZ addition. A similar pattern was observed for the degradation profile in vitro. GelMA+15%AZ fibers led to the highest bacterial inhibition. The presence of AZ, regardless of the concentration, did not pose significant toxicity. In vivo findings indicated higher blood vessel formation, mild inflammation, and mature and thick well-oriented collagen fibers interweaving with the engineered fibers. Altogether, AZ-laden photocrosslinkable GelMA fibers had adequate mechanical and degradation properties, with 15%AZ displaying significant antimicrobial activity without compromising biocompatibility.
Heat Shock Transcription Factor 2 Is Significantly Involved in Neurodegenerative Diseases, Inflammatory Bowel Disease, Cancer, Male Infertility, and Fetal Alcohol Spectrum Disorder: The Novel Mechanisms of Several Severe Diseases
Authors: Tokunaga Yasuko , Otsuyama Ken-Ichiro , Kakuta Shigeru , Hayashida Naoki
Published: November 2022

HSF (heat shock transcription factor or heat shock factor) was discovered as a transcription factor indispensable for heat shock response. Although four classical HSFs were discovered in mammals and two major HSFs, HSF1 and HSF2, were cloned in the same year of 1991, only HSF1 was intensively studied because HSF1 can give rise to heat shock response through the induction of various HSPs’ expression. On the other hand, HSF2 was not well studied for some time, which was probably due to an underestimate of HSF2 itself. Since the beginning of the 21st century, HSF2 research has progressed and many biologically significant functions of HSF2 have been revealed. For example, the roles of HSF2 in nervous system protection, inflammation, maintenance of mitosis and meiosis, and cancer cell survival and death have been gradually unveiled. However, we feel that the fact HSF2 has a relationship with various factors is not yet widely recognized; therefore, the biological significance of HSF2 has been underestimated. We strongly hope to widely communicate the significance of HSF2 to researchers and readers in broad research fields through this review. In addition, we also hope that many readers will have great interest in the molecular mechanism in which HSF2 acts as an active transcription factor and gene bookmarking mechanism of HSF2 during cell cycle progression, as is summarized in this review.
A 2D Porous Zinc-Organic Framework Platform for Loading of 5-Fluorouracil
Authors: Qin Liang , Liang Fenglan , Li Yan , Wu Jiana , Guan Shiyuan , Wu Meiyin , Xie Shiling , Luo Manshi , Ma Deyun
Published: November 2022

A hydrostable 2D Zn-based MOF, {[Zn(5-PIA)(imbm)]·2H2O}n (1) (5-H2PIA = 5-propoxy-isophthalic acid, imbm = 1,4-di(1H-imidazol-1-yl)benzene), was synthesized and structurally characterized. Complex 1 shows good water and thermal stability based on the TGA and PXRD analyses and displays a 2D framework with 1D channels of 4.8 × 13.8 and 10.0 × 8.3 Å2 along the a axis. The 5-fluorouracil (5-FU) payload in activated complex 1 (complex 1a) is 19.3 wt%, and the cumulative release value of 5-FU at 120 h was about 70.04% in PBS (pH 7.4) at 310 K. In vitro MTT assays did not reveal any cytotoxic effect of NIH-3T3 and HEK-293 cells when the concentration of 1 was below 500 μg/mL and 5 μg/mL, respectively. No morphological abnormalities were observed on zebrafish exposed to complex 1.
Antihypertensive Therapy and Incidence of Cancer
Authors: Loosen Sven H. , Schöler David , Luedde Mark , Eschrich Johannes , Luedde Tom , Gremke Niklas , Kalder Matthias , Kostev Karel , Roderburg Christoph
Published: November 2022

Background: Antihypertensive pharmacological therapy includes diuretics, beta-blockers, ACE inhibitors, calcium channel blockers and angiotensin II receptor blockers. Besides their use in arterial hypertension, these drugs also play a major role in the therapy of portal hypertension, heart failure and coronary artery disease. Systematic analyses on the possible influence of these medications on cancer incidence are lacking. Methods: By utilizing the Disease Analyzer database (IQVIA), 349,210 patients with antihypertensive drug prescriptions between 2010 and 2020 without a diagnosis of cancer prior to or at the date of initial drug prescription were included. Propensity score matching was carried out by 1:1:1:1:1 according to the five antihypertensive treatments. Cox regression analyses were performed to investigate an association between antihypertensive drugs and the incidence of cancer. Results: Patients who were diagnosed with cancer were treated with diuretics in 19.9% of cases, calcium channel blockers in 16.9% of cases, and angiotensin II receptor blockers, ACE inhibitors, or beta-blockers in 13.9%, 13.2% and 12.8% of cases, respectively. Cox regression models revealed that diuretic use positively correlated with liver cancer incidence (HR: 1.31, 95%CI: 1.12–2.63) and lymphoid/haematopoietic tissue cancer incidence (HR: 1.27, 95%CI: 1.10–1.46). Use of diuretics negatively correlated with the incidence of prostate (HR: 0.64, 95%CI: 0.53–0.78) and skin cancer (HR: 0.81, 95%CI: 0.72–0.92). Finally, a positive association was found between angiotensin II receptor inhibitors and prostate cancer incidence (HR: 1.50, 95%CI: 1.28–1.65). Conclusions: These data suggest that diuretic use might be associated with liver cancer and lymphoid/haematopoetic tissue cancer development.
Combined Neuro-Humoral Modulation and Outcomes in Patients with Chronic Heart Failure and Mildly Reduced or Preserved Ejection Fraction
Authors: Gori Mauro , Marini Marco , Gonzini Lucio , Carigi Samuela , De Gennaro Luisa , Gentile Piero , Leonardi Giuseppe , Orso Francesco , Tinti Denitza , Lucci Donata , Iacoviello Massimo , Navazio Alessandro , Ammirati Enrico , Municinò Annamaria , Benvenuto Manuela , Cassaniti Leonarda , Tavazzi Luigi , Maggioni Aldo Pietro , De Maria Renata
Published: November 2022

Pharmacotherapy of chronic heart failure with mildly reduced (HFmrEF) and preserved ejection fraction (HFpEF) remains challenging. We aimed to assess whether combined neuro-humoral modulation (NHM) (renin–angiotensin system inhibitors, betablockers, mineralocorticoid receptor antagonists) was differentially associated with outcome according to phenotype and age groups. Between 1999 and 2018 we recruited in a nationwide cardiology registry 4707 patients (HFmrEF n = 2298, HFpEF n = 2409) from three age groups: <65, 65–79 and 80+ years old. We analyzed clinical characteristics and 1 year all-cause mortality/cardiovascular hospitalization according to none/single, any double, or triple NHM. Prescription rates of no/single and triple NHM were 25.1% and 26.7% for HFmrEF; 36.5% and 17.9% for HFpEF patients, respectively. Older age was associated with higher prescription of no/single NHM in HFmrEF (ptrend = 0.001); the reverse was observed among HFpEF (ptrend = 0.005). Triple NHM increased over time in both phenotypes (all p for trend < 0.0001). Compared to no/single NHM, triple, but not double, NHM was associated with better outcomes in both HFmrEF (HR 0.700, 95%CI 0.505–0.969, p = 0.032) and HFpEF (HR 0.700, 95%CI 0.499–0.983, p = 0.039), with no interaction between NHM treatment and age groups (p = 0.58, p = 0.80, respectively). In a cardiology setting, among HF outpatients with EF > 40%, triple NHM treatment increased over time and was associated with better patient outcomes.
Treatment of Various Ocular Manifestation of Systemic Lupus Erythematosus with Therapeutic Plasma Exchange
Authors: Lee Ji-Hye , Jeon Ho-Wook , Moon Su-Jin , Lee Mee-Yon
Published: November 2022

The goal of this study is to describe a rare case of acute systemic lupus erythematosus (SLE) ocular involvement, followed by a rapid deterioration of the overall condition, and to then describe its successful treatment with therapeutic plasma exchange (TPE). In our case, a 21-year-old female, previously diagnosed with SLE, presented with a bilateral decreased vision for one week. Fundus examination and optical coherence tomography revealed subretinal fluid accumulation in both eyes and severe disc swelling with diffuse subretinal hemorrhages and perimacular whitening in the left eye. Despite systemic high-dose steroid therapy, the patient became worse, but immunosuppressive treatment was postponed due to fever and elevated serum leukocytes with the chance of systemic infection. She had undergone therapeutic plasma exchange (TPE) and was successfully treated. Preceding SLE ocular manifestation can be an indicator of the exacerbation of SLE, and TPE can be a treatment option for such progression.
The Loss-of-Function Mutation aldA67 Leads to Enhanced α-L-Rhamnosidase Production by Aspergillus nidulans
Authors: Orejas Margarita , MacCabe Andrew P.
Published: November 2022

In Aspergillus nidulans L-rhamnose is catabolised to pyruvate and L-lactaldehyde, and the latter ultimately to L-lactate, via the non-phosphorylated pathway (LRA) encoded by the genes lraA-D, and aldA that encodes a broad substrate range aldehyde dehydrogenase (ALDH) that also functions in ethanol utilisation. LRA pathway expression requires both the pathway-specific transcriptional activator RhaR (rhaR is expressed constitutively) and the presence of L-rhamnose. The deletion of lraA severely impairs growth when L-rhamnose is the sole source of carbon and in addition it abolishes the induction of genes that respond to L-rhamnose/RhaR, indicating that an intermediate of the LRA pathway is the physiological inducer likely required to activate RhaR. The loss-of-function mutation aldA67 also has a severe negative impact on growth on L-rhamnose but, in contrast to the deletion of lraA, the expression levels of L-rhamnose/RhaR-responsive genes under inducing conditions are substantially up-regulated and the production of α-L-rhamnosidase activity is greatly increased compared to the aldA+ control. These findings are consistent with accumulation of the physiological inducer as a consequence of the loss of ALDH activity. Our observations suggest that aldA loss-of-function mutants could be biotechnologically relevant candidates for the over-production of α-L-rhamnosidase activity or the expression of heterologous genes driven by RhaR-responsive promoters.
Understanding Place in Place-Based Planning: From Space- to People-Centred Approaches
Authors: Quintana Vigiola Gabriela
Published: November 2022

Place-based planning has been applied in the past two decades, and it has started being incorporated into planning policy in the past decade in the Global North. On the other hand, bottom-up approaches applied in the Global South, for example, in informal settlements, embed place-based concepts from their conception. One of the roots of this slow incorporation of place-based planning into policies is the lack of agreement on what a place is and how and by whom it is created. This paper applies a desktop study to answer the following: what are the different approximations of the topics of place and place-making? And how is the concept of place investigated in informal settlements? This paper discusses the different conceptions of place and identifies the two main perspectives toward place-making: space-centred and people-centred approaches. These perspectives share goals but differ in focus on how and by whom places are constructed. This paper also analyses how the topic of place has been addressed when discussing informal settlements and the fundamental disparity in the literature forming the concepts of place (mainly arising from the Global North) and the process of constructing places in the Global South, and how the latter can help inform place-based planning.
Study on the Solidification Effect of Dredger Fill by Microbial-Induced Calcium Precipitation (MICP)
Authors: Li Jun , Tian Lijun , Xu Yan , Tian Zefeng , Zhang Zhendong
Published: November 2022

This paper puts forward a new soft soil reinforcement technology—microbial-induced calcite precipitation (MICP) technology—which considers the problem of dredger fill soft-soil reinforcement in Dalian Taiping Bay. In this paper, the calcium carbonate content (CCC) and unconfined compressive strength (UCS) of microbial solidified dredger fill (MSDF) samples were determined using laboratory experiments. The microstructure and chemical composition of MSDF samples were studied by SEM–EDS and XRD. The failure and reinforcement mechanism of MSDF under different experimental conditions (ambient temperature, cementation solution concentration, and clay content) were investigated. The results showed that there was a certain residual strength after the peak strength of MSDF. With the increase of ambient temperature, the number of microorganisms increased, but the activities of urease, CCC, and UCS decreased. The UCS and CCC increased with the increase of cementation solution concentration, while they first increased and then decreased with the increase of clay content. The clay content enhanced the compactness of MSDF samples but reduced the soil permeability and weakened the mineralization. There were significant differences in the morphology of microbial-induced precipitation caused by different concentrations of cementation solution.
Influence of the Al Content on the Properties of Mechanically Alloyed CoCrFeNiMnXAl20−X High-Entropy Alloys
Authors: Thürlová Hana , Průša Filip
Published: November 2022

The equiatomic CoCrFeNiMn alloy prepared by mechanical alloying and spark plasma sintering underwent partial substitution of Mn by Al (5, 10 and 15 at.%) to determine its influence on mechanical properties and thermal stability. It was discovered that the higher the Al content, the higher the volume fraction of the hard phase with primitive cubic (PC) crystallographic lattice, which increases the hardness and strength of the alloys. The most promising mechanical properties have been achieved in the CoCrFeNiMn5Al15 alloy reaching the compressive yield strength (CYS) of 2135 ± 21 MPa and the ultimate compressive strength (UCS) of 2496 ± 21 MPa. All the prepared alloys showed good thermal stability as they maintained or only slightly reduced their initial hardness during the 100 h annealing at 800 °C. Furthermore, the higher the Al content, the higher the resistance against high-temperature oxidation. The oxidic layer changed its composition from Mn-oxides (CoCrFeNiMn15Al15 alloy) to Al-based oxides with exceptional protective properties.
Coupled Indirect Torque Control and Maximum Power Point Tracking Technique for Optimal Performance of 12/8 Switched Reluctance Generator-Based Wind Turbines
Authors: Zine Mahmoud , Chemsa Ali , Labiod Chouaib , Ikhlef Malika , Srairi Kamel , Benbouzid Mohamed
Published: November 2022

Maximum power point tracking (MPPT) techniques for wind turbines have a significant effect on renewable energy production. Therefore, the association of the indirect torque control of the switched reluctance generator (SRG) with the wind turbine considering the MPPT technique has been developed in this work. The proposed strategy has a great impact on the production of renewable energy using an SRG machine. The main steps to achieve the object of this work are: First, the wind turbine was modeled and simulated according to the MPPT. In the second step, the indirect torque control strategy, based on the hysteresis current control for SRG 12/8, was realized. This was undertaken using a proportional integral regulator and the hysteresis controller for the torque in order to obtain the appropriate switching based on an asymmetric bridge converter. Moreover, the SRG has high nonlinear characteristics. Thus, the modeling results of this kind of machine are obtained by the use of the finite element method, with its dynamic study performed by the unique estimation of the electromagnetic torque in its generator mode functioning. Finally, the indirect torque control technique of the SRG has also been associated with the MPPT technique to maximize the efficiency power coefficient. The obtained results approve and validate the efficiency of a proposed MPPT of the wind turbine associated with the SRG. This illustrates, simultaneously, the remarkable effects of the turn-switching angles on the operating performances and the high quality of the produced energy. The importance of the effect of varying the turn-switching angles is also presented and discussed.
Research on Energy Consumption Generation Method of Fuel Cell Vehicles: Based on Naturalistic Driving Data Mining
Authors: Ma Yangyang , Wang Pengyu , Li Bin , Li Jianhua
Published: November 2022

In this paper, an energy consumption generation method is proposed to accurately calculate the energy consumption of fuel cell vehicles (FCVs). A specific driver drives on a route (from Jilin University to FAW Volkswagen) for 331 working days (1 April 2020 to 28 July 2021) and collects more than 40,000 s of naturalistic driving data by means of a GPS receiver (FRII-D). To accurately calculate the energy consumption data of FCVs under actual driving cycles, naturalistic driving data mining is first studied. The principal component analysis (PCA) algorithm is used to reduce the dimension of the extracted driving cycle characteristic parameters, the K-means algorithm is used for driving cycle clustering, and the LVQ is used for driving cycle identification. Then, the characteristic parameters correlated to energy consumption are obtained based on the FCV model and regression analysis method. In addition, an energy consumption generation method is designed and proposed based on the characteristic parameters and identification results. Furthermore, the proposed energy consumption generation method can accurately calculate the energy consumption of FCVs, which also provides a reference for further research on the efficient energy management of FCVs.
Detecting Depression Using Single-Channel EEG and Graph Methods
Authors: Zhu Guohun , Qiu Tong , Ding Yi , Gao Shang , Zhao Nan , Liu Feng , Zhou Xujuan , Gururajan Raj
Published: November 2022

Objective: This paper applies graph methods to distinguish major depression disorder (MDD) and healthy (H) subjects using the graph features of single-channel electroencephalogram (EEG) signals. Methods: Four network features—graph entropy, mean degree, degree two, and degree three—were extracted from the 19-channel EEG signals of 64 subjects (26 females and 38 males), and then these features were forwarded to a support vector machine to conduct depression classification based on the eyes-open and eyes-closed statuses, respectively. Results: Statistical analysis showed that graph features with degree of two and three, the graph entropy of MDD was significantly lower than that for H (p < 0.0001). Additionally, the accuracy of detecting MDD using single-channel T4 EEG with leave-one-out cross-validation from H was 89.2% and 92.0% for the eyes-open and eyes-closed statuses, respectively. Conclusion: This study shows that the graph features of a short-term EEG can help assess and evaluate MDD. Thus, single-channel EEG signals can be used to detect depression in subjects. Significance: Graph feature analysis discovered that MDD is more related to the temporal lobe than the frontal lobe.
May the Force (Field) Be with You: On the Importance of Conformational Searches in the Prediction of NMR Chemical Shifts
Authors: Cuadrado Cristina , Daranas Antonio Hernández , Sarotti Ariel M.
Published: November 2022

NMR data prediction is increasingly important in structure elucidation. The impact of force field selection was assessed, along with geometry and energy cutoffs. Based on the conclusions, we propose a new approach named mix-J-DP4, which provides a remarkable increase in the confidence level of complex stereochemical assignments—100% in our molecular test set—with a very modest increment in computational cost.