bluuebunny/crossref_metadata_2025 huggingface dataset:
Specific Extracellular Vesicles, Generated and Operating at Synapses, Contribute to Neuronal Effects and Signaling
Authors: Meldolesi Jacopo
Published: May 2024

In all cell types, small EVs, very abundant extracellular vesicles, are generated and accumulated within MVB endocytic cisternae. Upon MVB fusion and exocytosis with the plasma membrane, the EVs are released to the extracellular space. In the central nervous system, the release of neuronal EVs was believed to occur only from the surface of the body and dendrites. About 15 years ago, MVB cisternae and EVs were shown to exist and function at synaptic boutons, the terminals’ pre- and post-synaptic structures essential for canonical neurotransmitter release. Recent studies have revealed that synaptic EVs are peculiar in many respects and heterogeneous with respect to other neuronal EVs. The distribution of synaptic EVs and the effect of their specific molecules are found at critical sites of their distribution. The role of synaptic EVs could consist of the modulation of canonical neurotransmitter release or a distinct, non-canonical form of neurotransmission. Additional roles of synaptic EVs are still not completely known. In the future, additional investigations will clarify the role of synaptic EVs in pathology, concerning, for example, circuits, trans-synaptic transmission, diagnosis and the therapy of diseases.
Correction: Wang et al. Role of Berberine Thermosensitive Hydrogel in Periodontitis via PI3K/AKT Pathway In Vitro. Int. J. Mol. Sci. 2023, 24, 6364
Authors: Wang Chang , Liu Chang , Liang Chen , Qu Xingyuan , Zou Xinying , Du Siyu , Zhang Qian , Wang Lei
Published: May 2024

In the original publication, there was a mistake in Figure 3 as published [...]
Diagnostic and Prognostic Value of Plasma GFAP in Sporadic Creutzfeldt–Jakob Disease in the Clinical Setting of Rapidly Progressive Dementia
Authors: Bentivenga Giuseppe Mario , Baiardi Simone , Mastrangelo Andrea , Zenesini Corrado , Mammana Angela , Rossi Marcello , Polischi Barbara , Capellari Sabina , Parchi Piero
Published: May 2024

The diagnostic and prognostic value of plasma glial fibrillary acidic protein (pl-GFAP) in sporadic Creutzfeldt–Jakob disease (sCJD) has never been assessed in the clinical setting of rapidly progressive dementia (RPD). Using commercially available immunoassays, we assayed the plasma levels of GFAP, tau (pl-tau), and neurofilament light chain (pl-NfL) and the CSF total tau (t-tau), 14-3-3, NfL, phospho-tau181 (p-tau), and amyloid-beta isoforms 42 (Aβ42) and 40 (Aβ40) in sCJD (n = 132) and non-prion RPD (np-RPD) (n = 94) patients, and healthy controls (HC) (n = 54). We also measured the CSF GFAP in 67 sCJD patients. Pl-GFAP was significantly elevated in the sCJD compared to the np-RPD and HC groups and affected by the sCJD subtype. Its diagnostic accuracy (area under the curve (AUC) 0.760) in discriminating sCJD from np-RPD was higher than the plasma and CSF NfL (AUCs of 0.596 and 0.663) but inferior to the 14-3-3, t-tau, and pl-tau (AUCs of 0.875, 0.918, and 0.805). Pl-GFAP showed no association with sCJD survival after adjusting for known prognostic factors. Additionally, pl-GFAP levels were associated with 14-3-3, pl-tau, and pl-NfL but not with CSF GFAP, Aβ42/Aβ40, and p-tau. The diagnostic and prognostic value of pl-GFAP is inferior to established neurodegeneration biomarkers. Nonetheless, pl-GFAP noninvasively detects neuroinflammation and neurodegeneration in sCJD, warranting potential applications in disease monitoring.
Physicochemical Properties and Antioxidant Activity of CRISPR/Cas9-Edited Tomato SGR1 Knockout (KO) Line
Authors: Kim Jin Young , Kim Dong Hyun , Kim Me-Sun , Jung Yu Jin , Kang Kwon Kyoo
Published: May 2024

Tomatoes contain many secondary metabolites such as β-carotene, lycopene, phenols, flavonoids, and vitamin C, which are responsible for antioxidant activity. SlSGR1 encodes a STAY-GREEN protein that plays a critical role in the regulation of chlorophyll degradation in tomato leaves and fruits. Therefore, the present study was conducted to evaluate the sgr1 null lines based on their physicochemical characteristics, the content of secondary metabolites, and the γ-Aminobutyric acid (GABA) content. The total soluble solids (TSS), titrated acidity (TA), and brix acid ratio (BAR) of the sgr1 null lines were higher than those of the wild type(WT). Additionally, the sgr1 null lines accumulated higher levels of flavor-inducing ascorbic acid and total carotenoids compared to WT. Also, the total phenolic content, total flavonoids, GABA content, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical content of the sgr1 null lines were higher than those of the WT. Therefore, these studies suggest that the knockout of the SGR1 gene by the CRISPR/Cas9 system can improve various functional compounds in tomato fruit, thereby satisfying the antioxidant properties required by consumers.
ABCB1 C1236T, G2677TA and C3435T Genetic Polymorphisms and Antidepressant Response Phenotypes: Results from a Portuguese Major Depressive Disorder Cohort
Authors: Santos Marlene , Lima Luis , Carvalho Serafim , Brandão Andreia , Barroso Fátima , Cruz Agostinho , Medeiros Rui
Published: May 2024

P-glycoprotein (P-GP) is a transporter molecule expressed on the apical surface of capillary endothelial cells of the Blood–Brain Barrier (BBB), whose activity heavily influences drug distribution, including antidepressants. This transporter is encoded by ABCB1 gene, and genetic variations within ABCB1 gene have been proposed to affect drug efflux and have been previously associated with depression. In this context, we aimed to evaluate the role of C1236T, G2677TA and C3435T ABCB1 genetic polymorphisms in antidepressant treatment phenotypes from a cohort of patients harboring Major Depressive Disorder. Patients enrolled in the study consisted of 80 individuals with Major Depressive Disorder, who took part in a 27-month follow-up study at HML, Portugal. To investigate the correlation between ABCB1 polymorphisms and antidepressant response phenotypes, DNA was extracted from peripheral blood, and C1236T, C3435T and G2677TA polymorphisms were genotyped with TaqMan® SNP Genotyping Assays. Despite the fact that the evaluated polymorphisms (C1236T, C3435T and G2677TA) were not associated with treatment resistant depression, or relapse, we observed that patients carrying TT genotype of the C3435T polymorphism remit earlier than the ones carrying CC or CT genotypes (10.2 weeks vs. 14.9 and 21.3, respectively, p = 0.028, Log-rank test). Since we found an association with C3435T and time to remission, and not to the absence of remission, we suggest that this polymorphism could have an impact on antidepressant drug distribution, and thus influence on the time to remission will occur, without influencing the risk of remission itself.
Special Issue “Cancer Immunotherapy: Tumor Microenvironment, Biomarker Discovery and Immune Resistance”
Authors: Chan Jason Yongsheng
Published: May 2024

Since the launch of this Special Issue entitled “Cancer Immunotherapy: Tumor Microenvironment, Biomarker Discovery and Immune Resistance”, the field of cancer immunotherapy has continued to witness rapid growth in the development of novel agents, improvements in our understanding of mechanisms of response and resistance, and the maturation of emerging technologies such as artificial intelligence, machine learning, single-cell sequencing and spatial profiling [...]
From Jane Doe to Sofia: DNA Extraction Protocol from Bones and Teeth without Liquid Nitrogen for Identifying Skeletal Remains
Authors: Stan Emanuela , Muresan Camelia-Oana , Dumache Raluca , Ciocan Veronica , Ungureanu Stefania , Mihailescu Alexandra , Daescu Ecaterina , Duda-Seiman Corina , Menghiu Gheorghita , Hutanu Delia , Enache Alexandra
Published: May 2024

DNA analysis plays a crucial role in forensic investigations, helping in criminal cases, missing persons inquiries, and archaeological research. This study focuses on the DNA concentration in different skeletal elements to improve human identification efforts. Ten cases of unidentified skeletal remains brought to the Institute of Forensic Medicine in Timisoara, Romania, underwent DNA analysis between 2019 and 2023. The results showed that teeth are the best source for DNA extraction as they contain the highest concentration of genetic material, at 3.68 ng/µL, compared to the petrous temporal bone (0.936 ng/µL) and femur bone (0.633 ng/µL). These findings highlight the significance of teeth in forensic contexts due to their abundant genetic material. Combining anthropological examination with DNA analysis enhances the understanding and precision of identifying human skeletal remains, thus advancing forensic science. Selecting specific skeletal elements, such as the cochlea or teeth, emerges as crucial for reliable genetic analyses, emphasizing the importance of careful consideration in forensic identification procedures. Our study concludes that automated DNA extraction protocols without liquid nitrogen represent a significant advancement in DNA extraction technology, providing a faster, more efficient, and less labor-intensive method for extracting high-quality DNA from damaged bone and tooth samples.
Additional Sex Combs-like Family Associated with Epigenetic Regulation
Authors: Kim Nackhyoung , Byun Sukyoung , Um Soo-Jong
Published: May 2024

The additional sex combs-like (ASXL) family, a mammalian homolog of the additional sex combs (Asx) of Drosophila, has been implicated in transcriptional regulation via chromatin modifications. Abnormal expression of ASXL family genes leads to myelodysplastic syndromes and various types of leukemia. De novo mutation of these genes also causes developmental disorders. Genes in this family and their neighbor genes are evolutionary conserved in humans and mice. This review provides a comprehensive summary of epigenetic regulations associated with ASXL family genes. Their expression is commonly regulated by DNA methylation at CpG islands preceding transcription starting sites. Their proteins primarily engage in histone tail modifications through interactions with chromatin regulators (PRC2, TrxG, PR-DUB, SRC1, HP1α, and BET proteins) and with transcription factors, including nuclear hormone receptors (RAR, PPAR, ER, and LXR). Histone modifications associated with these factors include histone H3K9 acetylation and methylation, H3K4 methylation, H3K27 methylation, and H2AK119 deubiquitination. Recently, non-coding RNAs have been identified following mutations in the ASXL1 or ASXL3 gene, along with circular ASXLs and microRNAs that regulate ASXL1 expression. The diverse epigenetic regulations linked to ASXL family genes collectively contribute to tumor suppression and developmental processes. Our understanding of ASXL-regulated epigenetics may provide insights into the development of therapeutic epigenetic drugs.
The Vital Role of Melatonin and Its Metabolites in the Neuroprotection and Retardation of Brain Aging
Authors: Bocheva Georgeta , Bakalov Dimitar , Iliev Petar , Tafradjiiska-Hadjiolova Radka
Published: May 2024

While primarily produced in the pineal gland, melatonin’s influence goes beyond its well-known role in regulating sleep, nighttime metabolism, and circadian rhythms, in the field of chronobiology. A plethora of new data demonstrates melatonin to be a very powerful molecule, being a potent ROS/RNS scavenger with anti-inflammatory, immunoregulatory, and oncostatic properties. Melatonin and its metabolites exert multiple beneficial effects in cutaneous and systemic aging. This review is focused on the neuroprotective role of melatonin during aging. Melatonin has an anti-aging capacity, retarding the rate of healthy brain aging and the development of age-related neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, multiple sclerosis, amyotrophic lateral sclerosis, etc. Melatonin, as well as its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), can reduce oxidative brain damage by shielding mitochondria from dysfunction during the aging process. Melatonin could also be implicated in the treatment of neurodegenerative conditions, by modifying their characteristic low-grade neuroinflammation. It can either prevent the initiation of inflammatory responses or attenuate the ongoing inflammation. Drawing on the current knowledge, this review discusses the potential benefits of melatonin supplementation in preventing and managing cognitive impairment and neurodegenerative diseases.
Curcumin Improves Neurogenesis in Alzheimer’s Disease Mice via the Upregulation of Wnt/β-Catenin and BDNF
Authors: Lou Shengchun , Gong Danfeng , Yang Mengting , Qiu Qing , Luo Jialie , Chen Tingting
Published: May 2024

Adult neurogenesis in the dentate gyrus (DG) is impaired during Alzheimer’s disease (AD) progression. Curcumin has been reported to reduce cell apoptosis and stimulate neurogenesis. This study aimed to investigate the influence of curcumin on adult neurogenesis in AD mice and its potential mechanism. Two-month-old male C57BL/6J mice were injected with soluble β-amyloid (Aβ1–42) using lateral ventricle stereolocalization to establish AD models. An immunofluorescence assay, including bromodeoxyuridine (BrdU), doublecortin (DCX), and neuron-specific nuclear antigen (NeuN), was used to detect hippocampal neurogenesis. Western blot and an enzyme-linked immunosorbent assay (ELISA) were used to test the expression of related proteins and the secretion of brain-derived neurotrophic factor (BDNF). A Morris water maze was used to detect the cognitive function of the mice. Our results showed that curcumin administration (100 mg/kg) rescued the impaired neurogenesis of Aβ1–42 mice, shown as enhanced BrdU+/DCX+ and BrdU+/NeuN+ cells in DG. In addition, curcumin regulated the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) -mediated glycogen synthase kinase-3β (GSK3β) /Wingless/Integrated (Wnt)/β-catenin pathway and cyclic adenosine monophosphate response element-binding protein (CREB)/BDNF in Aβ1–42 mice. Inhibiting Wnt/β-catenin and depriving BDNF could reverse both the upregulated neurogenesis and cognitive function of curcumin-treated Aβ1–42 mice. In conclusion, our study indicates that curcumin, through targeting PI3K/Akt, regulates GSK3β/Wnt/β-catenin and CREB/BDNF pathways, improving the adult neurogenesis of AD mice.
Serum Amyloid A3 Promoter-Luciferase Reporter Mice Are Useful for Early Drug-Induced Nephrotoxicity Detection
Authors: Kudo Ayane , Osedo Haruka , Aisyah Rahmawati , Yazawa Nao , Saliu Tolulope Peter , Miyata Kenshu , Kumrungsee Thanutchaporn , Yanaka Noriyuki
Published: May 2024

Early detection of drug-induced kidney injury is essential for drug development. In this study, multiple low-dose aristolochic acid (AA) and cisplatin (Cis) injections increased renal mRNA levels of inflammation, fibrosis, and renal tubule injury markers. We applied a serum amyloid A3 (Saa3) promoter-driven luciferase reporter (Saa3 promoter-luc mice) to these two tubulointerstitial nephritis models and performed in vivo bioluminescence imaging to monitor early renal pathologies. The bioluminescent signals from renal tissues with AA or CIS injections were stronger than those from normal kidney tissues obtained from normal mice. To verify whether the visualized bioluminescence signal was specifically generated by the injured kidney, we performed in vivo bioluminescence analysis after opening the stomachs of Saa3 promoter-luc mice, and the Saa3-mediated bioluminescent signal was specifically detected in the injured kidney. This study showed that Saa3 promoter activity is a potent non-invasive indicator for the early detection of drug-induced nephrotoxicity.
Unravelling the Function of the Sesquiterpene Cyclase STC3 in the Lifecycle of Botrytis cinerea
Authors: Coca-Ruiz Víctor , Suárez Ivonne , Aleu Josefina , Cantoral Jesús M. , González Celedonio , Garrido Carlos , Brito Nélida , Collado Isidro G.
Published: May 2024

The genome sequencing of Botrytis cinerea supplies a general overview of the map of genes involved in secondary metabolite synthesis. B. cinerea genomic data reveals that this phytopathogenic fungus has seven sesquiterpene cyclase (Bcstc) genes that encode proteins involved in the farnesyl diphosphate cyclization. Three sesquiterpene cyclases (BcStc1, BcStc5 and BcStc7) are characterized, related to the biosynthesis of botrydial, abscisic acid and (+)-4-epi-eremophilenol, respectively. However, the role of the other four sesquiterpene cyclases (BcStc2, BcStc3, BcStc4 and BcStc6) remains unknown. BcStc3 is a well-conserved protein with homologues in many fungal species, and here, we undertake its functional characterization in the lifecycle of the fungus. A null mutant ΔBcstc3 and an overexpressed–Bcstc3 transformant (OvBcstc3) are generated, and both strains show the deregulation of those other sesquiterpene cyclase-encoding genes (Bcstc1, Bcstc5 and Bcstc7). These results suggest a co-regulation of the expression of the sesquiterpene cyclase gene family in B. cinerea. The phenotypic characterization of both transformants reveals that BcStc3 is involved in oxidative stress tolerance, the production of reactive oxygen species and virulence. The metabolomic analysis allows the isolation of characteristic polyketides and eremophilenols from the secondary metabolism of B. cinerea, although no sesquiterpenes different from those already described are identified.
Lichen Sclerosus—Incidence and Comorbidity: A Nationwide Swedish Register Study
Authors: Jerkovic Gulin Sandra , Lundin Filippa , Eriksson Olle , Seifert Oliver
Published: May 2024

Background: Data on the incidence and comorbidity of Lichen sclerosus (LS), based on validated nationwide population-based registries, remains scarce. Objective: To explore the incidence and association of comorbidities with LS in Sweden, emphasizing its potential links to malignancies and autoimmune disorders. Methods: A population-based retrospective open cohort study was conducted using the National Patient Register to identify all individuals diagnosed with LS (ICD-10 code L90.0) from 1 January 2001 to 1 January 2021. The study included 154,424 LS patients and a sex and age matched control group of 463,273 individuals to assess the incidence and odds ratios for various cancers and premalignant conditions. Results: The incidence of LS in Sweden was 80.9 per 100,000 person per year, with higher incidence in females (114.4) than in males (47.2). LS patients showed an increased odds ratio for vulvar cancer (OR = 8.3; 95% CI = 7.5–9.0), penile cancer (OR = 8.9; 95% CI = 7.3–11.0), prostate cancer (OR = 1.2; 95% CI = 1.1–1.2), testicular cancer (OR = 1.4; 95% CI = 1.1–1.7), bladder cancer (OR = 1.1; 95% CI = 1.1–1.2), breast cancer (OR = 1.4; 95% CI = 1.3–1.4), leukoplakia of the vulva (OR = 253.5; 95% CI = 221.9–289.6), and leukoplakia of the penis (OR = 5.1; 95% CI = 4.9–5.4). Conclusions: This study underscores the significantly increased association of various cancers and premalignant conditions in LS patients, highlighting the critical need for efficacious treatment and diligent follow-up. The association between LS and autoimmune diseases further necessitates comprehensive investigation to understand the underlying mechanisms and clinical management implications. Future research is essential to confirm these findings and elucidate the role of LS in cancer development.
Results of a Web-Based Survey on 2565 Greek Migraine Patients in 2023: Demographic Data, Imposed Burden and Satisfaction to Acute and Prophylactic Treatments in the Era of New Treatment Options
Authors: Dermitzakis Emmanouil V. , Argyriou Andreas A. , Bilias Konstantinos , Barmpa Evangelia , Liapi Sofia , Rikos Dimitrios , Xiromerisiou Georgia , Soldatos Panagiotis , Vikelis Michail
Published: May 2024

Objective: The Greek Society of Migraine and Headache Patients conducted its third in-line population web-based survey in 2023 to ascertain if the burden of the disease and the patients’ satisfaction with conventional and novel migraine therapies are changing compared to our previous findings from 2018 and 2020. Methods: The sampling process was based on a random call to participants to reply to a specific migraine-focused self-administered questionnaire, including 83 questions in Greek, which was distributed nationwide through the online research software SurveyMonkey. Results: We eventually enrolled 2565 patients, the majority of which were females. Our findings clearly demonstrate that migraine is still a burdensome condition. The degree of its impact on all aspects of productivity depends on the monthly frequency of migraine and the response rates to acute and prophylactic treatments. A total of 1029 (42.4%) of the patients had visited the emergency room mainly for unresponsiveness to acute treatments or aura-related symptoms. Triptans seem to be partly effective as acute therapies. OnabotulinumtoxinA seems to be effective for almost half of chronic migraine patients (43.9%) to report adequate satisfaction with this treatment (27.8% were “fairly happy”, 10.6% were “very happy”, and 5.5% were “extremely happy”). Due to their high rates of preventative effectiveness, most respondents treated with anti-CGRP Mabs expressed their optimism concerning their future while living with their migraine (88.25%), as well as towards further improvements in their quality of life (82.8%) status, mostly with fremanezumab. Conclusions: The patients recognize the usefulness of anti-CGRP Mabs in migraine prevention and consequently seem to be more optimistic than before about living with migraine. Considering the market change that is anticipated with the use of gepants and ditans, larger longitudinal population-based studies are warranted to further explore if the new era of migraine therapeutics might further lessen the burden of the disease.
Validation of a New Scoring Method to Assess the Efficacy of Rapid Initiation and Titration of Combination Pharmacotherapy for Patients Hospitalized with Acute Decompensated Heart Failure with Reduced and Mildly Reduced Ejection Fraction
Authors: Asano Takaaki , Maeno Yoshio , Nakano Masataka , Taguri Masataka , Miyasaka Masaki , Nakai Daisuke , Miyazaki Itaru , Nasu Takahito , Tanimoto Shuzou , Masuda Naoki , Morino Yoshihiro , Isshiki Takaaki , Ogata Nobuhiko
Published: May 2024

Background: Despite the encouragement of early initiation and titration of guideline-directed medical therapy (GDMT) for the treatment of heart failure (HF), most patients do not receive an adequate type and dose of pharmacotherapy in the real world. Objectives: This study aimed to determine the efficacy of titrating composite GDMT in patients with HF with reduced and mildly reduced ejection fraction and to identify patient conditions that may benefit from titration of GDMT. Methods: This was a two-center, retrospective study of consecutive patients hospitalized with acute decompensated heart failure (ADHF). Patients were classified into two groups according to a scoring scale determined by combination and doses of four types of HF agents (ACEis/ARBs/ARNis, BBs, MRAs, and SGLT2is) at discharge. A score of 5 or greater was defined as titrated GDMT, and a score of 4 or less was regarded as sub-optimal medical therapy (MT). Results: A total of 979 ADHF patients were screened. After 553 patients were excluded based on exclusion criteria, 426 patients (90 patients in the titrated GDMT group and 336 patients in the sub-optimal MT group) were enrolled for the analysis. The median follow-up period was 612 (453–798) days. Following statistical adjustment using the propensity score weighting method, the 2-year composite endpoint (composite of cardiac death and HF rehospitalization) rate was significantly lower in the titrated GDMT group, at 19%, compared with the sub-optimal MT group: 31% (score 3–4 points) and 43% (score 0–2 points). Subgroup analysis indicated a marked benefit of titrated GDMT in particular patient subgroups: age < 80 years, BMI 19.0–24.9, eGFR > 20 mL/min/1.73 m2, and serum potassium level ≤ 5.5 mmol/L. Conclusions: Prompt initiation and dose adjustment of multiple HF medications, with careful monitoring of the patient’s physiologic and laboratory values, is a prerequisite for improving the prognosis of patients with heart failure.
Inhibition of Microbicidal Activity of Canine Macrophages DH82 Cell Line by Capsular Polysaccharides from Cryptococcus neoformans
Authors: LaRocque-de-Freitas Isabel F. , da Silva-Junior Elias Barbosa , Gemieski Leticia Paixão , da Silva Dias Lima Beatriz , Diniz-Lima Israel , de Carvalho Vivarini Aislan , Lopes Ulisses G. , Freire-de-Lima Leonardo , Morrot Alexandre , Previato José Osvaldo , Mendonça-Previato Lucia , Pinto-da-Silva Lucia Helena , Freire-de-Lima Celio G. , Decote-Ricardo Debora
Published: May 2024

Cryptococcus neoformans is a lethal fungus that primarily affects the respiratory system and the central nervous system. One of the main virulence factors is the capsule, constituted by the polysaccharides glucuronoxylomannan (GXM) and glucuronoxylomanogalactan (GXMGal). Polysaccharides are immunomodulators. One of the target cell populations for modulation are macrophages, which are part of the first line of defense and important for innate and adaptive immunity. It has been reported that macrophages can be modulated to act as a “Trojan horse,” taking phagocytosed yeasts to strategic sites or having their machinery activation compromised. The scarcity of information on canine cryptococcosis led us to assess whether the purified capsular polysaccharides from C. neoformans would be able to modulate the microbicidal action of macrophages. In the present study, we observed that the capsular polysaccharides, GXM, GXMGal, or capsule total did not induce apoptosis in the DH82 macrophage cell line. However, it was possible to demonstrate that the phagocytic activity was decreased after treatment with polysaccharides. In addition, recovered yeasts from macrophages treated with polysaccharides after phagocytosis could be cultured, showing that their viability was not altered. The polysaccharides led to a reduction in ROS production and the mRNA expression of IL-12 and IL-6. We observed that GXMGal inhibits MHC class II expression and GXM reduces ERK phosphorylation. In contrast, GXMGal and GXM were able to increase the PPAR-γ expression. Furthermore, our data suggest that capsular polysaccharides can reduce the microbicidal activity of canine macrophages DH82.
Efficacy of Essential Oil Vapours in Reducing Postharvest Rots and Effect on the Fruit Mycobiome of Nectarines
Authors: Remolif Giulia , Buonsenso Fabio , Schiavon Giada , Garello Marco , Spadaro Davide
Published: May 2024

Nectarines can be affected by many diseases, resulting in significant production losses. Natural products, such as essential oils (EOs), are promising alternatives to pesticides to control storage rots. This work aimed to test the efficacy of biofumigation with EOs in the control of nectarine postharvest diseases while also evaluating the effect on the quality parameters (firmness, total soluble solids, and titratable acidity) and on the fruit fungal microbiome. Basil, fennel, lemon, oregano, and thyme EOs were first tested in vitro at 0.1, 0.5, and 1.0% concentrations to evaluate their inhibition activity against Monilinia fructicola. Subsequently, an in vivo screening trial was performed by treating nectarines inoculated with M. fructicola, with the five EOs at 2.0% concentration by biofumigation, performed using slow-release diffusers placed inside the storage cabinets. Fennel, lemon, and basil EOs were the most effective after storage and were selected to be tested in efficacy trials using naturally infected nectarines. After 28 days of storage, all treatments showed a significant rot reduction compared to the untreated control. Additionally, no evident phytotoxic effects were observed on the treated fruits. EO vapors did not affect the overall quality of the fruits but showed a positive effect in reducing firmness loss. Metabarcoding analysis showed a significant impact of tissue, treatment, and sampling time on the fruit microbiome composition. Treatments were able to reduce the abundance of Monilinia spp., but basil EO favored a significant increase in Penicillium spp. Moreover, the abundance of other fungal genera was found to be modified.
Assessment of the Quality and Readability of Information Provided by ChatGPT in Relation to the Use of Platelet-Rich Plasma Therapy for Osteoarthritis
Authors: Fahy Stephen , Niemann Marcel , Böhm Peter , Winkler Tobias , Oehme Stephan
Published: May 2024

Objective: This study aimed to evaluate the quality and readability of information generated by ChatGPT versions 3.5 and 4 concerning platelet-rich plasma (PRP) therapy in the management of knee osteoarthritis (OA), exploring whether large language models (LLMs) could play a significant role in patient education. Design: A total of 23 common patient queries regarding the role of PRP therapy in knee OA management were presented to ChatGPT versions 3.5 and 4. The quality of the responses was assessed using the DISCERN criteria, and readability was evaluated using six established assessment tools. Results: Both ChatGPT versions 3.5 and 4 produced moderate quality information. The quality of information provided by ChatGPT version 4 was significantly better than version 3.5, with mean DISCERN scores of 48.74 and 44.59, respectively. Both models scored highly with respect to response relevance and had a consistent emphasis on the importance of shared decision making. However, both versions produced content significantly above the recommended 8th grade reading level for patient education materials (PEMs), with mean reading grade levels (RGLs) of 17.18 for ChatGPT version 3.5 and 16.36 for ChatGPT version 4, indicating a potential barrier to their utility in patient education. Conclusions: While ChatGPT versions 3.5 and 4 both demonstrated the capability to generate information of moderate quality regarding the role of PRP therapy for knee OA, the readability of the content remains a significant barrier to widespread usage, exceeding the recommended reading levels for PEMs. Although ChatGPT version 4 showed improvements in quality and source citation, future iterations must focus on producing more accessible content to serve as a viable resource in patient education. Collaboration between healthcare providers, patient organizations, and AI developers is crucial to ensure the generation of high quality, peer reviewed, and easily understandable information that supports informed healthcare decisions.
The Sound of Memory: Investigating Music Therapy’s Cognitive Benefits in Patients with Dementia—A Network Meta-Analysis of Randomized Controlled Trials
Authors: Ting Berne , Su Chen-Hsin , Chen Daniel Tzu-Li , Hsu Wei-Ti , Tsai Chia-Lin , Lin Pan-Yen , Jingling Li
Published: May 2024

Numerous previous studies have shown the effectiveness of music therapy in enhancing cognitive functions in patients with dementia. Despite this, robust evidence in this field, especially concerning the comparison of different music therapy types, is lacking. Therefore, randomized controlled trials (RCTs) focusing on music therapy and cognitive functions in dementia patients, termed by “music” AND “dementia” OR “Alzheimer’s disease” AND “cognitive”, were identified from primary electronic databases to conduct this network meta-analysis (NMA). The primary outcome focused on the impact on cognitive functions, and the secondary outcome was the comparison of dropout rates between the intervention groups and the usual care control groups. Standardized mean difference (SMD) values and the corresponding 95% confidence intervals (CIs) were computed for effect evaluation. This study protocol has been registered in IPLASY (INPLASY202430082). A total of 14 RCTs with 1056 participants were enrolled, examining interventions including Active Music Therapy (AMT), Active Music Therapy with Singing (AMT + Sing), Rhythmic Music Therapy (RMT), Listening to Music (LtM), and Singing (Sing). The results indicated that RMT, AMT + Sing, and AMT all significantly improve cognitive functions in dementia patients, of which the SMD were 0.76 (95% CI = 0.32–1.21), 0.79 (95% CI = 0.03–1.49), and 0.57 (0.18–0.96), respectively. Compared with the control group (usual care), no music therapy type was associated with an increased dropout risk. In conclusion, music therapy can improve cognitive functions in patients with dementia without increasing the risk of dropout, particularly RMT, AMT + Sing, and AMT.
Action-Based Fiscal Consolidations and Economic Growth
Authors: Brueckner Markus
Published: May 2024

This paper tests the hypothesis that action-based fiscal consolidations have a negative effect on GDP growth. Using the IMF’s dataset on action-based fiscal consolidations, instrumental variables’ regressions show that action-based fiscal consolidations have a significant positive effect on GDP growth. The instrumental variables’ regressions also show that action-based fiscal consolidations significantly increase investment and productivity. The findings presented in this paper thus strongly reject the hypothesis that action-based fiscal consolidations reduce growth. The paper argues that least squares estimates presented in previous literature suffer from negative reverse causality bias: GDP growth has a significant positive effect on both the likelihood and the magnitude of action-based fiscal consolidations. To uncover causal effects of action-based fiscal consolidations, researchers need to use an instrumental variables approach.
Patterns of Service Utilization across the Full Continuum of Care: Using Patient Journeys to Assess Disparities in Access to Health Services
Authors: Bambi Jonas , Dong Gracia Yunruo , Santoso Yudi , Moselle Ken , Dugas Sophie , Olobatuyi Kehinde , Rudnick Abraham , Chang Ernie , Kuo Alex
Published: May 2024

Healthcare organizations have a contractual obligation to the public to address population-level inequities to health services access and shed light on them. Various studies have focused on achieving equitable access to healthcare services for vulnerable patients. However, these studies do not provide a nuanced perspective based on the local reality across the full continuum of care. In previous work, graph topology was used to provide visual depictions of the dynamics of patients’ movement across a complex healthcare system. Using patients’ encounters data represented as a graph, this study expands on previous work and proposes a methodology to identify and quantify cohort-specific disparities in accessing healthcare services across the continuum of care. The result has demonstrated that a more nuanced approach to assessing access-to-care disparity is doable using patients’ patterns of service utilization from a longitudinal cross-continuum healthcare dataset. The proposed method can be used as part of a toolkit to support healthcare organizations that wish to structure their services to provide better care to their vulnerable populations based on the local realities. This provides a first step in addressing inequities for vulnerable patients in accessing healthcare services. However, additional steps need to be considered to fully address these inequities.
Effects of Different Carbon and Nitrogen Ratios on Yield, Nutritional Value, and Amino Acid Contents of Flammulina velutipes
Authors: Han Jiandong , Sun Ruixiang , Huang Chunyan , Xie Hongyan , Gao Xia , Yao Qiang , Yang Peng , Li Jin , Gong Zhiyuan
Published: May 2024

The carbon-to-nitrogen (C/N) ratio in the cultivation medium significantly influences the growth rate, vigor of mycelium, yield of fruiting bodies, and their nutritional composition. Recently, agricultural and forestry wastes have been increasingly used in cultivating Flammulina velutipes. However, systematic research on how these materials affect the nutritional and functional properties of the fruiting bodies is lacking. This study investigated the effects of different C/N ratios on F. velutipes cultivation. We evaluated the agronomic traits, nutritional composition, and flavor compounds of the fruiting bodies. Our findings reveal that an optimal C/N ratio of 27:1 in the composted substrates enhances the total yield of fruiting bodies, with 25.1% soybean straw as the primary raw material. This ratio also significantly increases the levels of crude protein, total amino acids, and essential amino acids in the fruiting bodies (p < 0.05). Fruiting bodies from the high-nitrogen (HN) treatment showed the highest content of umami amino acids and equivalent umami concentration value. Additionally, we employed an untargeted liquid chromatography–mass spectrometry (LC-MS)-based metabolomics approach to analyze the metabolite profiles of fruiting bodies cultivated in high-nitrogen (HN), medium-nitrogen (MN), and low-nitrogen (LN) substrates. We found that the carbon–nitrogen ratio can affect the flavor and quality of fruiting bodies by regulating amino acid biosynthesis and metabolism and other related pathways. Our results suggest that a C/N ratio of 27:1 offers numerous benefits for the cultivation of F. velutipes with comprehensive analyses and has promising application prospects.
Phage Biosensor for the Classification of Metastatic Urological Cancers from Urine
Authors: Juusti Vilhelmiina , Rannikko Antti , Laurila Anu , Sundvall Maria , Hänninen Pekka , Kulpakko Janne
Published: May 2024

Most of the annual 10 million cancer-related deaths are caused by metastatic disease. Survival rates for cancer are strongly dependent on the type of cancer and its stage at detection. Early detection remains a challenge due to the lack of reliable biomarkers and cost-efficient screening methods. Phage biosensors can offer a solution for early detection using non-invasive liquid biopsies. Here, we report the first results of the bifunctional phage biosensor to detect metastatic urological cancers from urine. A dye-sensitized phage library was used to select metastasis-related phage binders. After selection rounds, the most promising phage candidate was used to classify metastatic cancer from controls. Additionally, we applied one chemical sensor (phenoxazine non-fluorescent dye) to classify cancer from urine. A statistical significance (p = 0.0002) was observed between metastatic and non-metastatic cancer, with sensitivity of 70% and specificity of 79%. Furthermore, the chemical sensor demonstrated significance in detecting cancer (p < 0.0001) with a sensitivity of 71% and a specificity of 75%. Our data suggest a new promising field for urine biomarker research, and further evaluation with prospectively collected samples is ongoing. In conclusion, we report, for the first time, the potential of a chemical- and phage-based biosensor method to detect metastatic cancer using urine.
Research on Deformation Prediction of VMD-GRU Deep Foundation Pit Based on PSO Optimization Parameters
Authors: Liu Ronggui , Zhang Qing , Jiang Feifei , Zhou Juan , He Jianxia , Mao Zhongyang
Published: May 2024

As a key guarantee and cornerstone of building quality, the importance of deformation prediction for deep foundation pits cannot be ignored. However, the deformation data of deep foundation pits have the characteristics of nonlinearity and instability, which will increase the difficulty of deformation prediction. In response to this characteristic and the difficulty of traditional deformation prediction methods to excavate the correlation between data of different time spans, the advantages of variational mode decomposition (VMD) in processing non-stationary series and a gated cycle unit (GRU) in processing complex time series data are considered. A predictive model combining particle swarm optimization (PSO), variational mode decomposition, and a gated cyclic unit is proposed. Firstly, the VMD optimized by the PSO algorithm was used to decompose the original data and obtain the Internet Message Format (IMF). Secondly, the GRU model optimized by PSO was used to predict each IMF. Finally, the predicted value of each component was summed with equal weight to obtain the final predicted value. The case study results show that the average absolute errors of the PSO-GRU prediction model on the original sequence, EMD decomposition, and VMD decomposition data are 0.502 mm, 0.462 mm, and 0.127 mm, respectively. Compared with the prediction mean square errors of the LSTM, GRU, and PSO-LSTM prediction models, the PSO-GRU on the PTB0 data of VMD decomposition decreased by 62.76%, 75.99%, and 53.14%, respectively. The PTB04 data decreased by 70%, 85.17%, and 69.36%, respectively. In addition, compared to the PSO-LSTM model, it decreased by 8.57% in terms of the model time. When the prediction step size increased from three stages to five stages, the mean errors of the four prediction models on the original data, EMD decomposed data, and VMD decomposed data increased by 28.17%, 3.44%, and 14.24%, respectively. The data decomposed by VMD are more conducive to model prediction and can effectively improve the accuracy of model prediction. An increase in the prediction step size will reduce the accuracy of the deformation prediction. The PSO-VMD-GRU model constructed has the advantages of reliable accuracy and a wide application range, and can effectively guide the construction of foundation pit engineering.
Wenzhou TE: A First-Principle-Calculated Thermoelectric Materials Database
Authors: Fang Ying , Shao Hezhu
Published: May 2024

Since the implementation of the Materials Genome Project by the Obama administration in the United States, the development of various computational materials’ databases has fundamentally expanded the choice of industries such as materials and energy. In the field of thermoelectric materials, the thermoelectric figure of merit (ZT) quantifies the performance of the material. From the viewpoint of calculations for vast materials, the ZT values are not easily obtained due to their computational complexity. Here, we show how to build a database of thermoelectric materials based on first-principle calculations for the electronic and heat transport of materials. Firstly, the initial structures are classified according to the values of bandgap and other basic properties using the clustering algorithm K-means in machine learning, and high-throughput first principle calculations are carried out for narrow-bandgap semiconductors which exhibit a potential thermoelectric application. The present framework of calculations mainly includes a deformation potential module, an electrical transport performance module, a mechanical and a thermodynamic properties module. We have also set up a search webpage for the calculated database of thermoelectric materials, providing search facilities and the ability to view the related physical properties of materials. Our work may inspire the construction of more computational databases of first-principle thermoelectric materials and accelerate research progress in the field of thermoelectrics.
Microstructure and Texture Evolution in Cold-Rolled and Annealed Oxygen-Free Copper Sheets
Authors: Qin Jing , Li Xun , Wang Dongsheng , Zhou Chen , Hu Tongsheng , Wang Jingwen , Yang Youwen , Hu Yujun
Published: May 2024

Commercial oxygen-free copper sheets were cold-rolled with reduction rates ranging from 20% to 87% and annealed at 400, 500 and 600 °C. The microstructure and texture evolution during the cold-rolling and annealing processes were studied using optical microscopy (OM), scanning electron microscopy (SEM) and electron back-scattered diffraction (EBSD). The results show that the deformation textures of {123}<634> (S), {112}<111> (Copper) and {110}<112> (Brass) were continuously enhanced with the increase in cold-rolling reduction. The orientations along the α-oriented fiber converged towards Brass, and the orientation density of β fiber obviously increased when the rolling reduction exceeded 60%. The recrystallization texture was significantly affected by the cold-rolling reduction. After 60% cold-rolling reduction, Copper and S texture components gradually decreased, and the {011}<511> recrystallization texture component formed with the increase in annealing temperature. After 87% cold-rolling reduction, a strong Cube texture formed, and other textures were inhibited with the increase in annealing temperature. The strong Brass and S deformation texture was conducive to the formation of a strong Cube annealing texture. The density of the annealing twin boundary decreased with the increase in annealing temperature, and more annealing twin boundaries formed in the oxygen-free copper sheets with the increase in cold-rolling reduction.
Initial Characteristics of Alkali–Silica Reaction Products in Mortar Containing Low-Purity Calcined Clay
Authors: Jóźwiak-Niedźwiedzka Daria , Jaskulski Roman , Dziedzic Kinga , Brachaczek Aneta , Jarząbek Dariusz M.
Published: May 2024

An alkali–silica reaction (ASR) is a chemical process that leads to the formation of an expansive gel, potentially causing durability issues in concrete structures. This article investigates the properties and behaviour of ASR products in mortar with the addition of low-purity calcined clay as an additional material. This study includes an evaluation of the expansion and microstructural characteristics of the mortar, as well as an analysis of the formation and behaviour of ASR products with different contents of calcined clay. Expansion tests of the mortar beam specimens were conducted according to ASTM C1567, and a detailed microscopic analysis of the reaction products was performed. Additionally, their mechanical properties were determined using nanoindentation. This study reveals that with an increasing calcined clay content, the amount of the crystalline form of the ASR gel decreases, while the nanohardness increases. The Young’s modulus of the amorphous ASR products ranged from 5 to 12 GPa, while the nanohardness ranged from 0.41 to 0.67 GPa. The obtained results contribute to a better understanding of how the incorporation of low-purity calcined clay influences the ASR in mortar, providing valuable insights into developing sustainable and durable building materials for the construction industry.
Research on Slurry Flowability and Mechanical Properties of Cemented Paste Backfill: Effects of Cement-to-Tailings Mass Ratio and Mass Concentration
Authors: Li Yan , Fu Jianxin , Yang Jiguang , Wang Jie
Published: May 2024

The flowability and mechanical properties are increasingly crucial in the filling process of deep metal mines with mining depths exceeding 1000 m. The rheological properties of filling slurry in the pipeline were analyzed through rheological tests, L-tube self-flow tests, and semi-industrial loop tests. The results revealed that with an increase in the cement-to-tailings mass ratio (c/t ratio) and mass concentration, the slurry exhibited a higher flow resistance and decreased stowing gradient. During slurry transportation, the pressure loss in the straight pipe was positively correlated with the slurry flow rate, c/t ratio, and mass concentration. A uniaxial compressive strength (UCS) test was conducted to analyze the mechanical properties of the cemented paste backfill containing BMC (CCPB) in both standard and deep-underground curing environments. The UCS of the CCPB showed an increasing trend with the rise in curing age, mass concentration, and the c/t ratio. The comprehensive analysis concluded that when the c/t ratio is 1:4, and the mass concentration is approximately 74%, and parameters such as the slump, bleeding rate, and flowability of the filling slurry meet the criteria for conveying and goaf filling, resulting in a high-strength filling body.