Exploring the Therapeutic Potential of Camellia longii Orel & Luu Leaf Extracts for Memory Loss in Alzheimer's Disease: Novel Findings and Functional Food Applications.

Novel research on the chemical compositions and biochemical activities of Camellia longii Orel and Luu leaf extracts revealed valuable resources with potential applications in Alzheimer's disease treatment. Qualitative phytochemicals detected various compound groups, including polyphenols, saponins, tannins, flavonoids, alkaloids, amino acids, coumarins, and polysaccharides. HPLC-MS identified 23 compounds in C. longii leaves with compounds found at significant levels, including epicatechin gallate (17.12%), tryptophan (13.73%), isovitexin (12.91%), gallic acid (3.06%), and quercetin (3.06%). Interestingly, the ethanol extract (CLL-Ew) exhibited the highest extraction yield (26.6%) and potent antioxidant and acetylcholinesterase (AChE) inhibitory effects in vitro. In the Drosophila melanogaster model, CLL-Ew improved longevity, movement, and memory by reducing malondialdehyde and increasing glutathione levels. Docking simulations suggested that the above compounds bind tightly to AChE's active site, potentially contributing to memory enhancement. Interestingly, observations of male and female mice after administration of a dose of 5000 mg/kg C. longii leaf extract were recorded normally throughout the 14 day experiment. These findings highlight the potential of C. longii leaf extracts in functional foods and therapeutic interventions for memory impairment prevention and treatment.

Scanning the aged to minimize missed injury: An EAST multicenter study.

BACKGROUND: Despite the high incidence of blunt trauma in older adults, there is a lack of evidence-based guidance for computed tomography (CT) imaging in this population. We aimed to identify an algorithm to guide use of a Pan-Scan (Head/C-spine/Torso) or a Selective Scan (Head/C-spine ± Torso). We hypothesized that a patient's initial history and exam could be used to guide imaging. METHODS: We prospectively studied blunt trauma patients aged 65+ at 18 Level I/II trauma centers. Patients presenting >24 h after injury or who died upon arrival were excluded. We collected history and physical elements and final injury diagnoses. Injury diagnoses were categorized into CT body regions of Head/C-spine or Torso (chest, abdomen/pelvis, and T/L spine). Using machine learning and regression modeling as well as a priori clinical algorithms based, we tested various decision rules against our dataset. Our priority was to identify a simple rule which could be applied at the bedside, maximizing sensitivity (Sens) and negative predictive value (NPV) to minimize missed injuries. RESULTS: We enrolled 5,498 patients with 3,082 injuries. Nearly half (47.1%, n = 2,587) had an injury within the defined CT body regions. No rule to guide a Pan-Scan could be identified with suitable Sens/NPV for clinical use. A clinical algorithm to identify patients for Pan-Scan, using a combination of physical exam findings and specific high-risk criteria, was identified and had a Sens of 0.94 and NPV of 0.86 This rule would have identified injuries in all but 90 patients (1.6%) and would theoretically spare 11.9% (655) of blunt trauma patients a torso CT. CONCLUSIONS: Our findings advocate for Head/Cspine CT in all geriatric patients with the addition of torso CT in the setting of positive clinical findings and high-risk criteria. Prospective validation of this rule could lead to streamlined diagnostic care of this growing trauma population. LEVEL OF EVIDENCE: Level 2, Diagnostic Tests or Criteria.

Frizzled-6 promotes hematopoietic stem/progenitor cell mobilization and survival during LPS-induced emergency myelopoiesis.

Emergency hematopoiesis involves the activation of bone marrow hematopoietic stem/progenitor cells (HSPCs) in response to systemic inflammation by a combination of cell-autonomous and stroma-dependent signals and leads to their release from bone marrow and migration to periphery. We have previously shown that FZD6 plays a pivotal role in regulating HSPC expansion and long-term maintenance. Now we sought to better understand the underlying mechanisms. Using lipopolysaccharide (LPS)-induced emergency granulopoiesis as a model, we show that failed expansion was intrinsic to FZD6-deficient HSPCs but also required a FZD6-deficient environment. FZD6-deficient HSPCs became more strongly activated, but their mobilization to peripheral blood was impaired and they were more susceptible to inflammatory cell death, leading to enhanced release of pro-inflammatory cytokines in the marrow. These studies indicate that FZD6 has a protective effect in the bone marrow to prevent an overactive inflammatory response and further suggest that mobilization improves HSPC survival during bone marrow inflammation.

BMDD: a novel approach for IoT platform (broker-less and microservice architecture, decentralized identity, and dynamic transmission messages).

Undeniably, Internet of Things (IoT) devices are gradually getting better over time; and IoT-based systems play a significant role in our lives. The pervasiveness of the new essential service models is expanding, and includes self-driving cars, smart homes, smart cities, as well as promoting the development of some traditional fields such as agriculture, healthcare, and transportation; the development of IoT devices has not shown any sign of cooling down. On the one hand, several studies are coming up with many scenarios for IoT platforms, but some critical issues related to performance, speed, power consumption, availability, security, and scalability are not yet fully resolved. On the other hand, IoT devices are manufactured and developed by different organizations and individuals; hence, there is no unified standard (uniformity of IoT devices), i.e., sending and receiving messages among them and between them and the upper layer (e.g., edge devices). To address these issues, this paper proposes an IoT Platform called BMDD (Broker-less and Microservice architecture, Decentralized identity, and Dynamic transmission messages) that has a combination of two architectural models, including broker-less and microservices, with cutting-edge technologies such as decentralized identity and dynamic message transmission. The main contributions of this article are five-fold, including: (i) proposing broker-less and microservice for the IoT platform which can reduce single failure point of brokering architecture, easy to scale out and improve failover; (ii) providing a decentralized authentication mechanism which is suitable for IoT devices attribute (i.e., mobility, distributed); (iii) applying the Role-Based Access Control (RBAC) model for the authorization process; (iv) exploiting the gRPC protocol combined with the Kafka message queue enhances transmission rates, transmission reliability, and reduces power consumption in comparison with MQTT protocol; and (v) developing a dynamic message transmission mechanism that helps users communicate with any device, regardless of the manufacturer, since it provides very high homogeneity.

BioVAE: a pre-trained latent variable language model for biomedical text mining.

SUMMARY: Large-scale pre-trained language models (PLMs) have advanced state-of-the-art (SOTA) performance on various biomedical text mining tasks. The power of such PLMs can be combined with the advantages of deep generative models. These are examples of these combinations. However, they are trained only on general domain text, and biomedical models are still missing. In this work, we describe BioVAE, the first large-scale pre-trained latent variable language model for the biomedical domain, which uses the OPTIMUS framework to train on large volumes of biomedical text. The model shows SOTA performance on several biomedical text mining tasks when compared to existing publicly available biomedical PLMs. In addition, our model can generate more accurate biomedical sentences than the original OPTIMUS output. AVAILABILITY AND IMPLEMENTATION: Our source code and pre-trained models are freely available: https://github.com/aistairc/BioVAE. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Sentanyl: a comparison of blood fentanyl concentrations and naloxone dosing after non-fatal overdose.

INTRODUCTION: Non-pharmaceutical fentanyl and its analogs have driven striking increases in opioid-associated overdose deaths. These highly potent opioids can be found at low concentrations in biological specimens. Little is known regarding the concentrations of these substances among survivors of non-fatal overdoses. In a locale where fentanyl is responsible for the majority of non-fatal opioid overdoses, we compared the concentration of fentanyl in blood to naloxone dosing in the presence and absence of a concurrent sedative-hypnotic exposure. METHODS: In this pilot study, we enrolled adult patients presenting to the emergency department (ED) who: (1) arrived after an overdose requiring naloxone for the reversal of respiratory depression; and (2) who required venipuncture or intravenous access as part of their clinical care. Blood specimens (n = 20) underwent comprehensive toxicology testing, including the quantitation of fentanyl, fentanyl analogs, and naloxone, as well as the detection of common sedative-hypnotics and a wide range of other illicit and pharmaceutical substances. We then compared fentanyl concentrations to naloxone dosing in participants with and without a concomitant sedative-hypnotic exposure. RESULTS: Nineteen of twenty participants (95%) were exposed to fentanyl prior to their overdose; the remaining participant tested positive for heroin metabolites. No participants reported pharmaceutical fentanyl use. Fentanyl analogs - acetylfentanyl or carfentanil - were present in three specimens. In 11 cases, fentanyl and its metabolites were the only opioids identified. Among the fentanyl-exposed, blood concentrations ranged from <0.1-19 ng/mL with a mean of 6.2 ng/mL and a median of 3.6 ng/mL. There was no relationship between fentanyl concentration and naloxone dose administered for reversal. We detected sedative-hypnotics (including benzodiazepines, muscle relaxants, and antidepressants) in nine participants. Among the sedative-hypnotic exposed, fentanyl concentrations were lower, but naloxone dosing was similar to those without a concomitant exposure. CONCLUSIONS: In this study, we found that: 1) fentanyl was present in the blood of nearly all participants; 2) fentanyl concentrations were lower among study participants with concomitant sedative-hypnotic exposure; and 3) the dose of naloxone administered for overdose reversal was not associated with the measured fentanyl concentration in blood specimens. Our results underscore the role that tolerance and concomitant drug exposure play in the precipitation and resuscitation of management of opioid overdose.

Inhibition of Melanosis in Whiteleg Shrimp (Litopenaeus vannamei) during Refrigerated Storage Using Extracts of Different Avocado (Persea americana Mill.) By-Products.

Melanosis in shrimp usually leads to reduction in its shelf life and quality, which causes a significant loss in economic value of shrimp products. This study reports potential applications of nine ethanolic extracts of by-products, i.e., peel and/or seed from three Vietnamese avocado varieties as effective inhibitors of melanosis in whiteleg shrimp. Six out of nine shrimp samples treated with the prepared extracts (0.025%, w/v) reduced melanosis and lipid oxidation more significantly as compared to those treated with sodium metabisulfite (SMS, 1.25%, w/v) and control groups (treated with water) during 8-day storage at 4°C (P<0.05). These six extracts had mean gray values ranging from 47.0±0.7 to 57.3±0.4% were lower than those treated with SMS (mean gray of 39.8±0.4%). The inhibition of melanosis and lipid oxidation in shrimp for these extracts could be attributed to their high content of polyphenols [total phenolic content (TPC) from 44.5±1.1 to 144.7±1.9 mg gallic acid equivalents/g dried weight] and strong antioxidant activities [including 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, ferric reducing antioxidant power (FRAP), and tyrosinase enzyme inhibition]. Pearson statistical analysis showed strong correlation for melanosis inhibition to TPC and DPPH scavenging (r>0.80) followed by tyrosinase inhibition and FRAP (r>0.50). The findings obtained from this study suggest potential utilization of avocado by-product extracts as safe and cheap natural alternatives to traditional sulfites for anti-melanosis and shelf life extension of whiteleg shrimp.

DeepEventMine: end-to-end neural nested event extraction from biomedical texts.

MOTIVATION: Recent neural approaches on event extraction from text mainly focus on flat events in general domain, while there are less attempts to detect nested and overlapping events. These existing systems are built on given entities and they depend on external syntactic tools. RESULTS: We propose an end-to-end neural nested event extraction model named DeepEventMine that extracts multiple overlapping directed acyclic graph structures from a raw sentence. On the top of the bidirectional encoder representations from transformers model, our model detects nested entities and triggers, roles, nested events and their modifications in an end-to-end manner without any syntactic tools. Our DeepEventMine model achieves the new state-of-the-art performance on seven biomedical nested event extraction tasks. Even when gold entities are unavailable, our model can detect events from raw text with promising performance. AVAILABILITY AND IMPLEMENTATION: Our codes and models to reproduce the results are available at: https://github.com/aistairc/DeepEventMine. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Trendy e-cigarettes enter Europe: chemical characterization of JUUL pods and its aerosols.

The popularity and the high nicotine content of the American pod e-cigarette JUUL have raised many concerns. To comply with European law, the nicotine concentration in the liquids of the European version, which has been recently released on the market, is limited to below 20 mg/mL. This limit can possibly be circumvented by technological adjustments that increase vaporization and consequently, elevate nicotine delivery. In this study, we compare vapor generation and nicotine delivery of the initial European version, a modified European version, and the original American high-nicotine variant using a machine vaping set-up. Additionally, benzoic acid and carbonyl compounds are quantified in the aerosol. Further, concentrations of nicotine, benzoic acid, propylene glycol, and glycerol, along with the density and pH value of JUUL e-liquids have been assessed. Whereas the initial European version did not compensate for the low nicotine content in the liquid, we provide evidence for an increased vaporization by the modified European version. As a consequence, nicotine delivery per puff approximates the American original. Notably, this is not associated with an increased generation of carbonyl compounds. Our data suggest a similar addictiveness of the enhanced European version and the original American product.

Multilocus sequence typing of Cryptococcus neoformans var. grubii from Laos in a regional and global context.

Cryptococcosis causes approximately 180 000 deaths each year in patients with human immunodeficiency virus (HIV). Patients with other forms of immunosuppression are also at risk, and disease is increasingly recognized in apparently immunocompetent individuals. Cryptococcus neoformans var. grubii, responsible for the majority of cases, is distributed globally. We used the consensus ISHAM Multilocus sequence typing (MLST) scheme to define the population structure of clinical C. neoformans var. grubii isolates from Laos (n = 81), which we placed into the global context using published MLST data from other countries (total N = 1047), including a reanalysis of 136 Vietnamese isolates previously reported. We observed a phylogeographical relationship in which the Laotian population was similar to its neighbor Thailand, being dominated (83%) by Sequence Types (ST) 4 and 6. This phylogeographical structure changed moving eastwards, with Vietnam's population consisting of an admixture of isolates dominated by the ST4/ST6 (35%) and ST5 (48%) lineages. The ST5 lineage is the predominant ST reported from China and East Asia, where it accounts for >90% of isolates. Analysis of genetic distance (Fst) between different populations of C. neoformans var. grubii supports this intermediate structure of the Vietnamese population. The pathogen and host diversity reported from Vietnam provide the strongest epidemiological evidence of the association between ST5 and HIV-uninfected patients. Regional anthropological genetic distances suggest diversity in the C. neoformans var. grubii population across Southeast Asia is driven by ecological rather than human host factors. Where the ST5 lineage is present, disease in HIV-uninfected patients is to be expected.

Levels of selected analytes in the emissions of "heat not burn" tobacco products that are relevant to assess human health risks.

Consumers of combustible cigarettes are exposed to many different toxicologically relevant substances associated with negative health effects. Newly developed "heat not burn" (HNB) devices are able to contain lower levels of Harmful and Potentially Harmful Constituents (HPHCs) in their emissions compared to tobacco cigarettes. However, to develop toxicological risk assessment strategies, further independent and standardized investigations addressing HPHC reduction need to be done. Therefore, we generated emissions of a commercially available HNB product following the Health Canada Intense smoking regimen and analyzed total particulate matter (TPM), nicotine, water, aldehydes, and other volatile organic compounds (VOCs) that are major contributors to health risk. We show that nicotine yield is comparable to typical combustible cigarettes, and observe substantially reduced levels of aldehydes (approximately 80-95%) and VOCs (approximately 97-99%). Emissions of TPM and nicotine were found to be inconsistent during the smoking procedure. Our study confirms that levels of major carcinogens are markedly reduced in the emissions of the analyzed HNB product in relation to the conventional tobacco cigarettes and that monitoring these emissions using standardized machine smoking procedures generates reliable and reproducible data which provide a useful basis to assess exposure and human health risks.

Modulation of inflammatory gene expression by a bilberry ( Vaccinium myrtillus L.) extract and single anthocyanins considering their limited stability under cell culture conditions.

Studies with nonintestinal models indicate that anthocyanin-rich extracts can modulate inflammatory gene expression and may help prevent development of inflammatory bowel diseases (IBD). This work investigated the influence of a bilberry ( Vaccinium myrtillus L.) extract (BE) and comprising anthocyanins on pro-inflammatory genes in IFN-γ/IL-1ß/TNF-α stimulated human colon epithelial cells (T84) by qRT-PCR and cytokine arrays. Moreover, the stability of selected anthocyanins under cell culture conditions was examined to assess their anti-inflammatory properties. BE and single anthocyanins significantly inhibited the expression and secretion of IBD-associated pro-inflammatory mediators (TNF-α, IP-10, I-TAC, sICAM-1, GRO-α) in the stimulated cells. The anti-inflammatory activity thereby strongly depends on the aglycon structure (hydroxylation and methylation pattern) and the sugar moiety. In contrast to anthocyanidins, which were highly unstable in cell culture medium, suggesting that their degradation products might contribute to the inhibitory effects assigned to the parent compounds, anthocyanins have higher stability and may directly contribute to BE's effects.