Prognostic impact of beta-blocker use by N-terminal pro-brain natriuretic peptide level in acute heart failure patients.

AIMS: Both patients with heart failure (HF) with reduced ejection fraction (HFrEF) and those with HF with preserved ejection fraction (HFpEF) present with elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) and have multiple comorbidities; consequently, the prognostic effect of NT-proBNP according to beta-blocker (BB) use is unknown. METHODS: This retrospective study evaluated patients admitted for acute HF between January 2012 and December 2017 at Ulsan University Hospital. Clinical, echocardiographic, laboratory and drug prescription data, including BB data, were collected from the hospital database. Information on mortality was collected by reviewing medical records or using national death data. RESULTS: Of the 472 patients evaluated, 216 (45.8%) and 256 (54.2%) patients were and were not prescribed BB at discharge, respectively. A total of 224 (47.5%) patients died within a median follow-up duration of 44 months. The Kaplan-Meier analysis showed reduced all-cause mortality with BB in HFrEF (ejection fraction ≤ 40%) but not in HFpEF (ejection fraction > 40%). In the multivariate Cox regression analysis, transmitral to tissue Doppler imaging, early diastolic velocity ratio (E/E'), NT-proBNP and BB use were independent predictors of all-cause mortality in HFrEF. Meanwhile, haemoglobin and NT-proBNP levels were independent predictors of HFpEF. The NT-proBNP cut-off value for determining all-cause mortality was set to 4800 pg/mL. Among HFrEF patients with NT-proBNP < 4800 pg/mL, the survival rate was higher for patients with BB use than those with no BB use (log-rank P < 0.001). However, in the HFpEF group, the survival rate associated with BB use did not differ according to the NT-proBNP levels. Both HFrEF and HFpEF patients with NT-proBNP levels of ≥4800 pg/mL presented with multiple comorbidities, including lower body mass index and haemoglobin levels and higher creatinine levels, NT-proBNP levels and E/E'. CONCLUSION: In patients with acute HF, BB use is associated with reduced all-cause mortality in those with HFrEF but not in those with HFpEF. HFrEF patients with NT-proBNP levels of <4800 pg/mL treated with BB have a higher survival rate than those not treated with BB. However, this benefit is not seen in HFrEF patients with NT-proBNP levels of ≥4800 pg/mL or in all HFpEF patients, regardless of the NT-proBNP level. NT-proBNP levels are elevated in multiple comorbid conditions, and these comorbidities may contribute to the attenuated effects of BB on all-cause mortality.

Variation of Soil Bacterial Communities in Forest Soil Contaminated with Chainsaw Lubricants.

Pollutants can exist in the soil for a long time and alter the bacterial community. Using lubricants to prevent the wear of chainsaw blades is necessary for thinning activities and wood harvesting. We investigated the influences of soil contamination with chainsaw lubricants on soil bacterial communities. Bio-oil, mineral oil, and recycled oil were scattered on each treatment to investigate variations in soil bacterial structure during treated periods using the Illumina MiSeq sequencing platform. The results obtained were 5943 ASVs, 5112 ASVs, and 6136 ASVs after treatment at one month, six months, and twelve months, respectively. There was a significant difference in Shannon and Simpson indices between treatments and controls. A total of 46 bacterial genera with an average relative abundance of more than 1.0% were detected in all soil samples. Massilia was the most common genus detected in control at one month, with an average relative abundance of 14.99%, while Chthoniobacter was the most abundant genus detected in bio-oil, mineral oil, and recycled oil treatments at one month, with an average relative abundance of 13.39%, 14.32%, and 10.47%, respectively. Among the three chainsaw lubricants, bio-oil and mineral oil had fewer impacts than recycled oil. The abundances of several functional bacteria groups in the bio-oil treatment were higher than in other treatments and controls. Our results indicated that different chainsaw lubricants and their time of application affected the soil bacterial community composition.

The complete mitochondrial genome of a wood-decaying fungus Vanderbylia fraxinea (Polyporaceae, Polyporales).

Vanderbylia fraxinea (Bull.) D.A. Reid, 1973 is an important wood-inhabiting fungus that plays a significant role in nutrient recycling in most forest ecosystems. In this study, the complete mitochondrial genome of V. fraxinea was characterized through de novo assembly using Illumina sequencing data and genome annotation. The mitochondrial genome is a circular molecule of 115,473 bp with a GC content of 28.66%. It comprises a total of 62 genes. Among these, 36 are protein-coding genes including 21 free-standing open reading frames (ORFs), 24 transfer RNA genes, and two ribosomal RNA genes. Core gene set commonly found in fungal mitochondrial genomes is also present in this genome, such as the apocytochrome b (cob), three subunits of the cytochrome c oxidase (cox1, cox2, and cox3), seven subunits of the NADH dehydrogenase (nad1, nad2, nad3, nad4, nad4L, nad5, and nad6), and three subunits of the ATP synthase (atp6, atp8, and atp9), as well as ribosomal RNA subunits (rns and rnl) and a set of transfer RNA genes. Phylogenetic analysis of the protein-coding sequences from the mitochondrial genome revealed a close relationship between V. fraxinea and the Ganoderma species within the Polyporaceae family.

NXP081, DNA Aptamer-Vitamin C Complex Ameliorates DNFB-Induced Atopic Dermatitis in Balb/c Mice.

Atopic dermatitis (AD) is a chronic inflammatory disease characterized by dry and itchy skin. Recently, it has been reported that oxidative stress is involved in skin diseases, possibly including AD. Vitamin C, also referred to as ascorbic acid, is a vital water-soluble compound that functions as an essential nutrient. It plays a significant role as both an antioxidant and an additive in various pharmaceutical and food products. Despite the fact that vitamin C is easily oxidized, we have developed NXP081, a single-stranded DNA aptamer that selectively binds to vitamin C, thereby inhibiting its oxidation. The objective of the current research was to examine the impact of NXP081, an animal model of AD induced by 2,4-dinitrofluorobenzene (DNFB). The experimental drug NXP081, when taken orally, showed promising results in reducing inflammation and improving the skin conditions caused by DNFB. The administration of NXP081 resulted in a significant reduction in ear swelling and a noticeable improvement in the appearance of skin lesions. In addition, the administration of NXP081 resulted in a significant decrease in the migration of mast cells in the skin lesions induced by DNFB. Moreover, NXP081 inhibited the production of interferon-gamma (IFN-γ) in CD4+ T cells that were activated and derived from the lymph nodes. Our findings provide useful information about the anti-inflammatory effect of NXP081 on AD.

Circadian control of cisplatin-DNA adduct repair and apoptosis in culture cells.

Cisplatin, a widely prescribed chemotherapeutic agent for treating solid tumors, induces DNA adducts and activates cellular defense mechanisms, including DNA repair, cell cycle checkpoint control, and apoptosis. Considering the circadian rhythmicity displayed by most chemotherapeutic agents and their varying therapeutic efficacy based on treatment timing, our study aimed to investigate whether the circadian clock system influences the DNA damage responses triggered by cisplatin in synchronized cells. We examined the DNA damage responses in circadian-synchronized wild-type mouse embryonic fibroblasts (WT-MEF; clock-proficient cells), cryptochrome1 and 2 double knock-out MEF (CRYDKO; clock-deficient cells), and mouse hepatocarcinoma Hepa1c1c7 cells. Varying the treatment time resulted in a significant difference in the rate of platinum-DNA adduct removal specifically in circadian-synchronized WT-MEF, while CRYDKO did not exhibit such variation. Moreover, diurnal variation in other DNA damage responses, such as cell cycle checkpoint activity indicated by p53 phosphorylation status and apoptosis measured by DNA break frequency, was observed only in circadian-synchronized WT-MEF, not in CRYDKO or mouse hepatocarcinoma Hepa1c1c7 cells. These findings highlight that the DNA damage responses triggered by cisplatin are indeed governed by circadian control exclusively in clock-proficient cells. This outcome bears potential implications for enhancing or devising chronotherapy approaches for cancer patients.

Blockchain-Based Federated Learning System: A Survey on Design Choices.

The vanilla federated learning is made for a trusted environment, while in contrast, its actual use cases require collaborations in an untrusted setting. For this reason, using blockchain as a trusted platform to run federated learning algorithms has gained traction lately and has become a significant research interest. This paper performs a literature survey on state-of-the-art blockchain-based federated learning systems and analyzes several design patterns researchers often take to solve existing issues through blockchain. We find about 31 design item variations throughout the whole system. Each design is further analyzed to find pros and cons, considering fundamental metrics such as robustness, efficiency, privacy, and fairness. The result shows a linear relationship between fairness and robustness in which, if we focus on improving fairness, it will indirectly become more robust. Furthermore, improving all those metrics altogether is not viable because of the efficiency trade-off. Finally, we classify the surveyed papers to spot which designs are popular among researchers and determine which areas require immediate improvements. Our investigation shows that future blockchain-based federated learning systems require more effort regarding model compression, asynchronous aggregation, system efficiency evaluation, and the application for cross-device settings.

Correction: Witanto et al. Distributed Data Integrity Verification Scheme in Multi-Cloud Environment. Sensors 2023, 23, 1623.

The authors make the following corrections to the published paper [...].

Early rituximab treatment reduces long-term disability in aquaporin-4 antibody-positive neuromyelitis optica spectrum.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) causes relapsing inflammatory attacks in the central nervous system, leading to disability. As rituximab, a B-lymphocyte-depleting monoclonal antibody, is an effective in preventing NMOSD relapses, we hypothesised that earlier initiation of rituximab can also reduce long-term disability of patients with NMOSD. METHODS: This multicentre retrospective study involving 19 South Korean referral centres included patients with NMOSD with aquaporin-4 antibodies receiving rituximab treatment. Factors associated with the long-term Expanded Disability Status Scale (EDSS) were assessed using multivariable regression analysis. RESULTS: In total, 145 patients with rituximab treatment (mean age of onset, 39.5 years; 88.3% female; 98.6% on immunosuppressants/oral steroids before rituximab treatment; mean disease duration of 121 months) were included. Multivariable analysis revealed that the EDSS at the last follow-up was associated with time to rituximab initiation (interval from first symptom onset to initiation of rituximab treatment). EDSS at the last follow-up was also associated with maximum EDSS before rituximab treatment. In subgroup analysis, the time to initiation of rituximab was associated with EDSS at last follow-up in patients aged less than 50 years, female and those with a maximum EDSS score ≥6 before rituximab treatment. CONCLUSIONS: Earlier initiation of rituximab treatment may prevent long-term disability worsening in patients with NMOSD, especially among those with early to middle-age onset, female sex and severe attacks.

Long-term survival benefits of intrathecal autologous bone marrow-derived mesenchymal stem cells (Neuronata-R®: lenzumestrocel) treatment in ALS: Propensity-score-matched control, surveillance study.

Objective: Neuronata-R® (lenzumestrocel) is an autologous bone marrow-derived mesenchymal stem cell (BM-MSC) product, which was conditionally approved by the Korean Ministry of Food and Drug Safety (KMFDS, Republic of Korea) in 2013 for the treatment of amyotrophic lateral sclerosis (ALS). In the present study, we aimed to investigate the long-term survival benefits of treatment with intrathecal lenzumestrocel. Methods: A total of 157 participants who received lenzumestrocel and whose symptom duration was less than 2 years were included in the analysis (BM-MSC group). The survival data of placebo participants from the Pooled-Resource Open-Access ALS Clinical Trials (PROACT) database were used as the external control, and propensity score matching (PSM) was used to reduce confounding biases in baseline characteristics. Adverse events were recorded during the entire follow-up period after the first treatment. Results: Survival probability was significantly higher in the BM-MSC group compared to the external control group from the PROACT database (log-rank, p < 0.001). Multivariate Cox proportional hazard analysis showed a significantly lower hazard ratio for death in the BM-MSC group and indicated that multiple injections were more effective. Additionally, there were no serious adverse drug reactions found during the safety assessment, lasting a year after the first administration. Conclusion: The results of the present study showed that lenzumestrocel treatment had a long-term survival benefit in real-world ALS patients.

Distributed Data Integrity Verification Scheme in Multi-Cloud Environment.

Most existing data integrity auditing protocols in cloud storage rely on proof of probabilistic data possession. Consequently, the sampling rate of data integrity verification is low to prevent expensive costs to the auditor. However, in the case of a multi-cloud environment, the amount of stored data will be huge. As a result, a higher sampling rate is needed. It will also have an increased cost for the auditor as a consequence. Therefore, this paper proposes a blockchain-based distributed data integrity verification protocol in multi-cloud environments that enables data verification using multi-verifiers. The proposed scheme aims to increase the sampling rate of data verification without increasing the costs significantly. The performance analysis shows that this protocol achieved a lower time consumption required for verification tasks using multi-verifiers than a single verifier. Furthermore, utilizing multi-verifiers also decreases each verifier's computation and communication costs.