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Intratumoral heterogeneity in epidermal growth factor receptor (EGFR)-mutant mutant non-small-cell lung cancer (NSCLC) explains the mixed responses to EGFR-tyrosine kinase inhibitors (TKIs). However, some studies showed tumors with low abundances of EGFR mutation still respond to EGFR-TKI, and the mechanism remained undetermined. Extracellular vesicles (EVs) can transmit antiapoptotic signals between drug-resistant and drug-sensitive cells. Herein, we profiled EVs from EGFR-mutant cells to identify a novel mechanism explaining why heterogenous EGFR-mutant NSCLC patients still respond to EGFR-TKIs. We first demonstrated that the EVs from EGFR-mutant changes the wild-type cells’ sensitivity to gefitinib by adding EV directly or coculturing EGFR wild-type (CL1-5) cells and EGFR-mutant (PC9) cells. In animal studies, only the combined treatment of PC9 EV and gefitinib delayed the tumor growth of CL1-5 cells. MicroRNA analysis comparing EV miRNAs from PC9 cells to those from CL1-5 cells showed that mir200 family members are most abundant in PC9 EVs. Furthermore, mir200a and mir200c were found upregulated in plasma EVs from good responders to EGFR-TKIs. Finally, the transfection of CL1-5 cells with miR200c inactivates downstream signaling pathways of EGFR, the EMT pathway, and enhances gefitinib sensitivity. Overall, our results suggest that in heterogeneous EGFR-mutant NSCLC, tumor cells transmit EV miRNAs that may affect sensitivity to EGFR-TKIs and provide potential prognostic biomarkers for EGFR-mutant NSCLC.

Beyond fertility, follicle-stimulating hormone (FSH) may exert action on adipocytes, which are the major source of adiponectin and leptin, linking to insulin resistance. Therefore, we evaluated the relationships between FSH and adipocyte-derived hormones. This cross-sectional study enrolled postmenopausal women aged 40–65 years. The variables measured in this study included clinical parameters, fasting levels of sex hormones, glucose, insulin, and adipokines. A total of 261 women without breast cancer, 88 women with breast cancer receiving tamoxifen, and 59 women with breast cancer receiving additional gonadotropin-releasing hormone analogs were enrolled in this study. Significant differences in the levels of adiponectin, leptin, and FSH were observed between the non-breast cancer group and the breast cancer groups. Spearman’s rank test revealed significant associations of FSH with either body mass index (BMI) or homeostatic model assessment of insulin resistance (HOMA-IR) values in the non-breast cancer group. After adjusting for BMI, age, and menopause duration, FSH levels were significantly associated with adiponectin (p < 0.001) and the leptin-to-adiponectin ratio (p = 0.008) in the non-breast cancer group, but they were only significantly associated with adiponectin (p = 0.001) in the breast cancer group receiving tamoxifen. Our data show that FSH levels are independently associated with adiponectin levels in postmenopausal women, suggesting that adiponectin may link FSH to metabolic relationships in postmenopausal female.

Abstract The quest for sustainable agricultural practices has led to a surge in research focused on innovative wastewater treatment methods. This review explores the emerging biological treatment approaches designed to address the challenges of eco-friendly agricultural wastewater treatment and subsequent reuse. The investigation centers around three novel techniques: constructed wetlands, algae-based systems, and microbial fuel cells. Constructed wetlands (CWs) mimic natural processes to treat agricultural wastewater, providing habitat for various plant species that collaboratively remove contaminants. Algae-based systems(ABs) harness the photosynthetic prowess of algae to absorb nutrients and pollutants, producing biomass that can be repurposed. Meanwhile, microbial fuel cells (MFCs) employ microorganisms to break down organic matter in wastewater while generating electricity as a valuable byproduct. This review aims to provide insights into the potential of these biological treatment methods to revolutionize wastewater management in agriculture. By mitigating environmental impact, conserving water resources, and yielding reusable outputs, these techniques will offer a sustainable pathway towards addressing the pressing challenges of agricultural wastewater treatment and enhancing the overall ecological balance.

Non-ionic deep eutectic solvents (DESs) are non-ionic designer solvents with various applications in catalysis, extraction, carbon capture, and pharmaceuticals. However, discovering new DES candidates is challenging due to a lack of efficient tools that accurately predict DES formation. The search for DES relies heavily on intuition or trial-and-error processes, leading to low success rates or missed opportunities. Recognizing that hydrogen bonds (HBs) play a central role in DES formation, we aim to identify HB features that distinguish DES from non-DES systems and use them to develop machine learning (ML) models to discover new DES systems. We first analyze the HB properties of 38 known DES and 111 known non-DES systems using their molecular dynamics (MD) simulation trajectories. The analysis reveals that DES systems have two unique features compared to non-DES systems: The DESs have ① more imbalance between the numbers of the two intra-component HBs and ② more and stronger inter-component HBs. Based on these results, we develop 30 ML models using ten algorithms and three types of HB-based descriptors. The model performance is first benchmarked using the average and minimal receiver operating characteristic (ROC)-area under the curve (AUC) values. We also analyze the importance of individual features in the models, and the results are consistent with the simulation-based statistical analysis. Finally, we validate the models using the experimental data of 34 systems. The extra trees forest model outperforms the other models in the validation, with an ROC-AUC of 0.88. Our work illustrates the importance of HBs in DES formation and shows the potential of ML in discovering new DESs.

Abstract Background As cows transition from pregnancy to lactation, free fatty acids (FFA) are mobilized from adipose tissues (AT) through lipolysis to counter energy deficits. In clinically healthy cows, lipolysis intensity is reduced throughout lactation; however, if FFA release exceeds tissue demands or the liver’s metabolic capacity, lipid byproducts accumulate, increasing cows’ risk of metabolic and infectious disease. Endocannabinoids (eCBs) and their congeners, N-acylethanolamines (NAEs), are lipid-based compounds that modulate metabolism and inflammation. Their synthesis and release depend upon the availability of FFA precursors and the abundance of synthesizing and degrading enzymes and transporters. Therefore, we hypothesized that eCB production and transcription of endocannabinoid system components are modulated by lipolysis pathways in adipocytes. To test this hypothesis, we stimulated canonical (isoproterenol, 1 µmol/L; ISO) and inflammatory (lipopolysaccharide, 1 µg/mL; LPS) lipolysis pathways in adipocytes isolated from the AT of 5 Holstein dairy cows. Following, we assessed lipolysis intensity, adipocytes’ release of eCBs, and transcription of endocannabinoid system components. Results We found that ISO and LPS stimulated lipolysis at comparable intensities. Exposure to either treatment tended to elevate the release of eCBs and NAEs by cultured adipocytes; however, specific eCBs and NAEs and the transcriptional profiles differed by treatment. On one hand, ISO enhanced adipocytes’ release of 2-arachidonoylglycerol (2-AG) but reduced NAE production. Notably, ISO enhanced the cells’ expression of enzymes associated with 2-AG biosynthesis (INPP5F, GDPD5, GPAT4), transport (CD36), and adipogenesis (PPARG). Conversely, LPS enhanced adipocytes’ synthesis and release of N-arachidonoylethanolamide (AEA). This change coincided with enhanced transcription of the NAE-biosynthesizing enzyme, PTPN22, and adipocytes’ transcription of genes related to eCB degradation (PTGS2, MGLL, CYP27B1). Furthermore, LPS enhanced adipocytes’ transcription of eCB and NAE transporters (HSPA1A, SCP2) and the expression of the anti-adipogenic ion channel, TRPV3. Conclusions Our data provide evidence for distinct modulatory roles of canonical and inflammatory lipolysis pathways over eCB release and transcriptional regulation of biosynthesis, degradation, transport, and ECS signaling in cows’ adipocytes. Based on our findings, we conclude that, within adipocytes, eCB production and ECS component expression are, at least in part, mediated by lipolysis in a pathway-dependent manner. These findings contribute to a deeper understanding of the molecular mechanisms underlying metabolic regulation in dairy cows’ AT, with potential implications for prevention and treatment of inflammatory and metabolic disorders. Graphical Abstract

Abstract Terrestrial groundwater travels through subterranean estuaries before reaching the sea. Groundwater‐derived nutrients drive coastal water quality, primary production, and eutrophication. We determined how dissolved inorganic nitrogen (DIN), dissolved inorganic phosphorus (DIP), and dissolved organic nitrogen (DON) are transformed within subterranean estuaries and estimated submarine groundwater discharge (SGD) nutrient loads compiling > 10,000 groundwater samples from 216 sites worldwide. Nutrients exhibited complex, nonconservative behavior in subterranean estuaries. Fresh groundwater DIN and DIP are usually produced, and DON is consumed during transport. Median total SGD (saline and fresh) fluxes globally were 5.4, 2.6, and 0.18 Tmol yr−1 for DIN, DON, and DIP, respectively. Despite large natural variability, total SGD fluxes likely exceed global riverine nutrient export. Fresh SGD is a small source of new nutrients, but saline SGD is an important source of mostly recycled nutrients. Nutrients exported via SGD via subterranean estuaries are critical to coastal biogeochemistry and a significant nutrient source to the oceans.

BackgroundDry eye disease (DED) is commonly caused by excessive tear film evaporation due to Meibomian gland dysfunction (MGD). There is a need for DED treatment options that address tear evaporation and benefit patients across a broad range of demographic and disease characteristics. This study evaluated treatment effects of perfluorohexyloctane ophthalmic drop (formerly NOV03) in the pooled dataset from 2 pivotal clinical trials in patients with DED associated with MGD, both in the overall population and in patient subgroups based on sex, age, and baseline severity of eye dryness.MethodsPooled data from 2 similarly designed, phase 3, randomized controlled trials (GOBI, MOJAVE) were analyzed. Patients aged ≥18 years with DED administered perfluorohexyloctane (n=614) or hypotonic (0.6% solution) saline control (n=603) four times daily for 8 weeks. Primary endpoints were total corneal fluorescein staining (tCFS) score (National Eye Institute scale, 0-15) and eye dryness visual analog scale (VAS) score (0-100). Efficacy was evaluated using analysis of covariance among patient subgroups (male and female, older [≥65 years] and younger [18 to

IntroductionBurns and other injuries requiring plastic and/or reconstructive surgery (BPRS) are lifechanging, often unexpected, and increase the risk of psychiatric morbidity. There are no published studies we are aware of that explores the applicability of psychological models to BPRS patients. Cognitive behavioural therapy (CBT) is the benchmark treatment in mental health but may be less effective in physical health settings. Metacognitive therapy (MCT)can be more effective than CBT in mental health settings and shows promise in reducing anxiety and depression symptoms in people with cancer and cardiac disease. The present study explored the psychological experiences (feelings, thoughts, and coping strategies) of BPRS patients, and whether the concepts underpinning cognitive and metacognitive models can be elicited from these accounts.MethodSemi structured interviews were conducted with 11 patients recruited from a BPRS psychology service. Data was analysed using Thematic Analysis. Patients described a range of emotions including low mood, anxiety, anger, guilt, loss, and negative thinking.ResultsFrom the perspective of the cognitive model, there were examples of each of 10 pre-specified distorted thinking types (cognitive distortions), and patient talk seemed to fit problem-specific cognitive models. From the perspective of the metacognitive model, all patients described the “cognitive attentional syndrome,” i.e., how they engaged in repetitive negative thinking (worry, rumination) and thought-focused regulation strategies. Patient talk also demonstrated both positive and negative metacognitive beliefs.ConclusionThe implications of applying the findings from each model to clinical practice are discussed. The metacognitive model may offer benefits in clinical practice that should be investigated further.

Background: Influenza represents a significant global health burden for individuals and society. This study assessed the burden of medically attended influenza at a tertiary medical center in Lebanon to describe the demographics, risk factors, and outcomes prior to the COVID-19 pandemic. Methods: This was a retrospective review of patients who tested positive for the influenza virus during three seasons between July 1, 2016 to June 30, 2019, at the American University of Beirut Medical Center. Results: A total of 2049 patients who tested positive for influenza were analyzed. Influenza A accounted for 79.6 % of cases, and influenza B for 19.7 %, with influenza activity starting in October/November and peaking in December/January. Older age above 65 years (AOR=3.584), obesity (AOR=2.183), and chronic conditions such as chronic lung diseases (AOR=1.832), and bacterial co-infection (AOR= 2.834) were found to be independent risk factors for developing complications. Viral co-infection increased the likelihood of death tenfold. Vaccinated patients had a shorter mean hospital stay duration and a lower intensive care unit admission rate. Conclusion: The burden of medically attended influenza at our tertiary medical center in Lebanon prior to the COVID-19 pandemic was high. Vaccination decreased the likelihood of complications leading to intensive care unit admission in patients at risk.

This study focuses on the removal of nitrate ions from aqueous solutions using rice husk activated carbon (RHAC). The RHAC was subjected to characterization via Fourier transform infrared (FTIR), scanning electron microscopy coupled with energy dispersive spectroscopy (SEM-EDS), and X-ray florescence (XRF) to ascertain its functional groups, surface morphology, and oxide/elemental composition, respectively. Batch experiments were conducted to assess the impact of nitrate concentration, bed height, and number of packing layers on removal efficiency. FTIR spectra revealed favorable sorption-related functional groups within RHAC, while SEM analysis indicated the presence of effective sorption sites on its surface. EDS analysis of the rice husk adsorbent before adsorption (RHBS) demonstrated a significant composition of Si (42.20%), O (35.30%), and Ca (12.33%). The batch study unveiled a concentration-dependent decrease in nitrate removal efficiency, alongside the enhanced performance with increased bed height and number of packing layers. Kinetic data fitting favored the Yoon–Nelson and Adams–Bohart models. Overall, RHAC exhibited efficient nitrate ion removal, with column performance notably improved by utilizing multiple packing layers. These results will enhance our understanding of the mechanisms involved in removing nitrate ions and highlight the potential effectiveness of RHAC, especially when utilized with multiple packing arrangements in column setups.

Background: Antenatal care (ANC) is crucial to reducing maternal and neonatal deaths, but few studies examined adolescent girls’ and young women’s ANC utilisation and knowledge in Ghana. Aim: To assess adolescents’ and young mothers’ knowledge of ANC, utilisation and factors influencing its use in Ghana. Setting: Tano North Municipality, Ahafo Region. Methods: This community-based, cross-sectional study involved 440 adolescent and young mothers (between 10 and 24 years). A structured questionnaire was employed to collect data face-to-face. Descriptive and statistical analyses were performed, and p 0.05 was considered statistically significant. Results: Of the 440 respondents, most were aged 20–24 years (61.2%), married (30.0%), Christians (78.2%), completed junior high school (JHS) (47.8%) and traders (38.9%). Postnatal mothers were 71.6% (315), and all had utilised ANC services. Antenatal care knowledge was good among 75% (330) respondents, with no significant variation by age. Religion influenced knowledge, with Muslims having lower knowledge. Antenatal care utilisation was high ( 50%) among those aged 15–19 years, married, Christians, JHS graduates and traders. Age, marital status and employment type significantly influenced ANC utilisation. Individuals in the age group 15–19 years and married women demonstrated higher odds of utilising ANC services. Casual workers and unemployed respondents were found to have lower odds of utilising ANC services compared to traders. Conclusion: Age, marital status, and employment type influenced ANC utilisation in the Ahafo Region. Adolescent mothers under 15 years had lower rates, requiring targeted interventions to improve pregnancy outcomes. Contribution: This study highlights the knowledge and factors influencing ANC use in Ahafo Region and adds to the existing research evidence on ANC.

Recent technological advances have enabled comprehensive analyses of the previously uncharacterized microbial community in the gastrointestinal tracts of numerous animal species; however, the gut microbiota of several species, such as the endangered proboscis monkey (Nasalis larvatus) examined in this study, remains poorly understood. Our study sought to establish the first comprehensive data on the gut microbiota of free-ranging foregut-fermenting proboscis monkeys and to determine how their microbiota are affected locally by environmental factors, i.e. geographical distance, and social factors, i.e. the number of adult females within harem groups and the number of adults and subadults within non-harem groups, in a riverine forest in Sabah, Malaysian Borneo. Using 16S rRNA gene sequencing of 264 faecal samples collected from free-ranging proboscis monkeys, we demonstrated the trend that their microbial community composition is not particularly distinctive compared with other foregut- and hindgut-fermenting primates. The microbial alpha diversity was higher in larger groups and individuals inhabiting diverse vegetation (i.e. presumed to have a diverse diet). For microbial beta diversity, some measures were significant, showing higher values with larger geographical distances between samples. These results suggest that social factors such as increased inter-individual interactions, which can occur with larger groups, as well as physical distances between individuals or differences in dietary patterns, may affect the gut microbial communities.

Summary: Background: Antimicrobial consumption continues to rise globally and contributes to the emergence and spread of antimicrobial resistance. This study aimed to evaluate antimicrobial prescribing patterns in a selected tertiary hospital in Tanzania. Methods: This cross-sectional study was conducted for one year (September 2021–September 2022) at Mbeya Zonal Referral Hospital, a public hospital in the southern highlands zone of Tanzania. Data on clinical diagnosis, laboratory tests, prescribed antimicrobials, and prescribers' designations were collected through a custom eMedical system, aligning antimicrobials with the WHO's 2021 AWaRe classification. Descriptive analysis was performed to assess the pattern of antimicrobial prescriptions. Results: Of 2,293 antimicrobial prescriptions, 62.41% were ACCESS, 37.42% were WATCH, and 0.17% fell in the RESERVE categories. Metronidazole, accounting for 23.8%, was the most commonly prescribed antimicrobial. More than 50% of the ACCESS and WATCH prescriptions were justified by laboratory diagnosis and were predominantly prescribed by clinicians. A very small proportion of prescriptions (

This paper presents a wide incident angle, wideband, and polarization-insensitive unit cell frequency-selective surface (FSS) on single- and double-glazing glass. The 5G signal losses due to the shielding of building materials lead to high penetration losses that degrade the data rates, energy, and spectral density. The transmission coefficient of glass is lower than that of the materials used in buildings. So, investigating and enhancing radio frequency signal losses on glassy windows at sub-6GHz frequency band is crucial to increase the transmission coefficient. This paper uses three different transparent materials: ITO-PET film, silver nanowires (AgNWs) on a polymer substrate, and silver on a pet substrate as an FSS coating material for glassy windows to enhance the transmission coefficient at the n77 and n78 bands. The optimization of unit cell parameters was implemented using the Trust Region Framework (TRF) algorithm. The investigation for single and double glazing has shown that the thicker the glass, the lower the transmission coefficient. Moreover, the simulation result of the proposed FSS can support up to ${85}^{o}$ and ${75}^{o}$ for single- and double-glazing glass, respectively. A maximum of 17 dB enhancement was obtained from single-glazing glass, and a maximum of 10 dB enhancement was obtained from double-glazing glass. Thus, the designed FSS structure can enhance 5G signal transmission from outdoors to indoors.

Abstract Introduction The study aimed to evaluate multi-symptom relief of dry eye manifestations with the use of propylene glycol-hydroxypropyl-guar (PG-HPG) nanoemulsion lubricant eye drops, among subjects with dry eye disease (DED). Methods This was a post-marketing, prospective, single-arm study conducted in the USA. Subjects aged ≥ 18 years, with tear breakup time (TBUT) ≤ 10 s for both eyes, dry eye questionnaire-5 (DEQ-5) “watery eyes” symptom score 1–4, symptoms of burning/stinging, sore and tired eyes as determined by impact of dry eye on everyday living—symptom bother (IDEEL-SB) questionnaire, and IDEEL-SB score 16–65 were included. Subjects were required to complete IDEEL-SB and DEQ-5 at days 0, 14 ± 2, and 28 ± 2, and self-administer one drop of PG-HPG four times daily for 28 ± 2 days. Primary endpoints were change from baseline at day 28 in symptoms of sore, stinging/burning, and tired eyes on IDEEL-SB; and symptom of watery eyes on DEQ-5. Other endpoints evaluated were corneal staining and TBUT at baseline and day 28 ± 2; symptom relief (5-point Likert scale) at day 28 ± 2, and safety. Results Of 119 subjects enrolled, 95 completed the study (mean ± SD age 61.2 ± 13.0 years; female 69.5%). Mean IDEEL-SB scores reduced significantly from baseline at day 28 for symptoms of aching/sore eyes (change from baseline − 1.0 ± 1.1), burning/stinging eyes (change from baseline − 1.1 ± 0.9), and tired eyes (change from baseline − 1.1 ± 1.0) (all p

Objective: To report the microbiological profile of the pathogens implicated in blood stream infections (BSI) in hospitalized coronavirus disease 2019 (COVID-19) patients and to examine the risk factors associated with multidrug-resistant organisms (MDROs) causing BSI. Patients and Methods: Between March 2020 and September 2021, 1647 patients were hospitalized with COVID-19 at the American University of Beirut. From 85 patients, 299 positive blood cultures were reported to the Infection Control and Prevention Program. The BSI was defined as 1 positive blood culture for bacterial or fungal pathogens. The following organisms were considered MDROs: methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus spp, carbapenem-resistant Enterobacterales spp., carbapenem-resistant Pseudomonas aeruginosa, MDR Acinetobacter baumannii only susceptible to colistin or tigecycline, and Candida auris. Results: We identified 99 true positive BSI events. Gram-negative bacteria accounted for 38.4 %, followed by Gram-positive bacteria (37.4%), and fungi (24.2%). The most isolated species were Candida spp. (23%), 3 of which were C. auris, followed by Enterobacterales spp. (13%), Enterococcus spp. (12%), S. aureus (9%), P. aeruginosa (9%), and A. baumannii (3%). The MDROs represented 26% of the events. The overall mortality rate was 78%. The time to acquisition of BSI in patients with MDROs was significantly longer compared with that of non-MDROs (20.2 days vs 11.2 days). And there was a significantly shorter time from acquisition of BSI to mortality between MDROs and non-MDROs (1.5 vs 8.3 days). Conclusion: Rigorous infection prevention and control measures and antimicrobial stewardship are important to prevent antimicrobial resistance progression, especially in low-resource settings.

Background: Despite multiple reports of increased incidence of bacterial respiratory tract infections following COVID-19 globally, the microbiology is not yet fully elucidated. In this study, we describe the microbiology of bacterial infections and the prevalence of multidrug resistant organisms (MDROs) in hospitalized COVID-19 patients with community-acquired pneumonia (CAP), and hospital-acquired pneumonia (HAP) which includes both non-ventilated hospital acquired pneumonia (NVHAP) and ventilator-associated pneumonia (VAP). To our knowledge, this is the first study that compares the microbiology of VAP and NVHAP in COVID-19 patients. Methods: This is a longitudinal retrospective cohort study conducted at the American University of Beirut Medical Center (AUBMC), a tertiary-care centre in Lebanon. Adult patients with confirmed COVID-19 and concurrent bacterial respiratory infections with an identifiable causative organism who were hospitalized between March 2020 and September 2021 were included. Bacterial isolates identified in hospital-acquired pneumonia (HAP) were divided into 3 groups based on the time of acquisition of pneumonia after admission: hospital day 3–14, 15–28 and 29–42. Results: Out of 1674 patients admitted with COVID-19, 159 (9.5%) developed one or more respiratory infections with an identifiable causative organism. Overall, Gram-negative bacteria were predominant (84%) and Stenotrophomonas maltophilia was the most common pathogen, particularly in HAP. Among 231 obtained isolates, 59 (26%) were MDROs, seen in higher proportion in HAP, especially among patients with prolonged hospital stay (> 4 weeks). Non-fermenter Gram-negative bacilli (NFGNB) (OR = 3.52, p-value

Glycogen storage disease type III (GSDIII) is a hereditary glycogenosis caused by deficiency of the glycogen debranching enzyme (GDE), an enzyme, encoded by Agl, enabling glycogen degradation by catalyzing alpha-1,4-oligosaccharide side chain transfer and alpha-1,6-glucose cleavage. GDE deficiency causes accumulation of phosphorylase-limited dextrin, leading to liver disorder followed by fatal myopathy. Here, we tested the capacity of the new autophagosomal activator GHF-201 to alleviate disease burden by clearing pathogenic glycogen surcharge in the GSDIII mouse model Agl−/−. We used open field, grip strength, and rotarod tests for evaluating GHF-201’s effects on locomotion, a biochemistry panel to quantify hematological biomarkers, indirect calorimetry to quantify in vivo metabolism, transmission electron microscopy to quantify glycogen in muscle, and fibroblast image analysis to determine cellular features affected by GHF-201. GHF-201 was able to improve all locomotion parameters and partially reversed hypoglycemia, hyperlipidemia and liver and muscle malfunction in Agl−/− mice. Treated mice burnt carbohydrates more efficiently and showed significant improvement of aberrant ultrastructural muscle features. In GSDIII patient fibroblasts, GHF-201 restored mitochondrial membrane polarization and corrected lysosomal swelling. In conclusion, GHF-201 is a viable candidate for treating GSDIII as it recovered a wide range of its pathologies in vivo, in vitro, and ex vivo.

Abstract Background The COVID-19 pandemic and its associated lockdowns accelerated the uptake of remote services, however, the integration of teleaudiology into regular clinical practice has been slow, with audiologists reporting several barriers and mixed attitudes. To develop effective strategies and solutions to enhance teleaudiology services and facilitate their acceptance beyond the pandemic, a better understanding of the factors influencing audiologist’s attitudes and usage is needed. The purpose of this study was to explore the attitudes towards and usage of teleaudiology by audiologists prior to and during the COVID-19 pandemic. We aimed to uncover underlying factors influencing teleaudiology adoption to identify potential barriers and opportunities that could inform interventions and future developments. Method and results Two cross-sectional surveys were administered to audiologists between September and October in 2018 and 2021. Questions addressed issues regarding quality of care, satisfaction, and perceived benefits of teleaudiology. Survey items based on the COM-B behaviour model were also included in the 2021 survey. Data were analysed using descriptive and non-parametric statistics. Eighty audiologists completed the 2018 survey and 105 audiologists completed the 2021 survey. In 2021, teleaudiology users reported increased quality of care, quality of relationships with clients and client satisfaction compared to non-users. However, among teleaudiology users, there was a decrease in quality of care, relationships with new clients and job satisfaction in 2021 compared to 2018. The COM-B framework helped identify the major barriers for non-users of teleaudiology such as lack of training, unclear guidelines, and concerns about service quality. Conclusion The attitudes towards teleaudiology for clinicians before and during the COVID-19 pandemic were investigated, revealing a substantial increase in usage and varying effects on client satisfaction, clinician job satisfaction and service quality. Key potential barriers and factors influencing usage were identified. Targeted solutions may include providing training, scheduling regular teleaudiology appointments to build confidence, and developing reliable tools and technologies to improve remote hearing care.

Summary: Inflammation is consistently linked to dysmetabolism. In transgenic mice (Def+/+) model the neutrophilic peptide, alpha defensin, proved atherogenic. This phenotype occurred despite favorable cholesterol and glucose levels, and lower body weight and blood pressure. In this study, integration of metabolic&behavioral phenotyping system, endocrine, biochemical and mitochondrial assessment, pathological and immunohistochemical tests, and multiple challenge tests was established to explore the metabolic impact of alpha defensin. Compared to the control group, Def+/+ mice exhibited lower total energy expenditure and carbohydrate utilization, and higher fat oxidation. Their ACTH-cortisol and thyroid profiles were intact. Intriguingly, they had low levels of glucagon, with high ammonia, uric acid, triglyceride, and lactate. Mitochondrial evaluations were normal. Overall, defensin-induced hypoglucagonemia is associated with lipolysis, restricted glucose oxidation, and enhanced wasting. Def+/+ mice may be a useful model for studying the category of lean, apparently metabolically healthy, and atherosclerotic phenotype, with insight into a potential inflammatory-metabolic link.

Objective: Non-alcoholic fatty liver disease (NAFLD) involves hepatic accumulation of intracellular lipid droplets via incompletely understood processes. Here, we report distinct and cooperative NAFLD roles of LysTTT-5′tRF transfer RNA fragments and microRNA miR-194-5p. Methods: Combined use of diet induced obese mice with human-derived oleic acid-exposed Hep G2 cells revealed new NAFLD roles of LysTTT-5′tRF and miR-194-5p. Results: Unlike lean animals, dietary-induced NAFLD mice showed concurrent hepatic decrease of both LysTTT-5′tRF and miR-194-5p levels, which were restored following miR-132 antisense oligonucleotide treatment which suppresses hepatic steatosis. Moreover, exposing human-derived Hep G2 cells to oleic acid for 7 days co-suppressed miR-194-5p and LysTTT-5′tRF levels while increasing lipid accumulation. Inversely, transfecting fattened cells with a synthetic LysTTT-5′tRF mimic elevated mRNA levels of the metabolic regulator β-Klotho while decreasing triglyceride amounts by 30% within 24 h. In contradistinction, antisense suppression of miR-194-5p induced accumulation of its novel target, the NAFLD-implicated lipid droplet-coating PLIN2 protein. Further, two out of 15 steatosis-alleviating screened drug-repurposing compounds, Danazol and Latanoprost, elevated miR-194-5p or LysTTT-5′tRF levels. Conclusion: Our findings highlight the different yet complementary roles of miR-194-5p and LysTTT-5′tRF and offer new insights into the complex roles of small non-coding RNAs and the multiple pathways involved in NAFLD pathogenesis.

Abstract Landscape structure plays a key role in mediating a variety of ecological processes affecting biodiversity patterns; however, its precise effects and the mechanisms underpinning them remain unclear. While the effects of landscape structure have been extensively investigated both empirically and theoretically from a metapopulation perspective, the effects of spatial structure at the landscape scale remain poorly explored from a metacommunity perspective. Here, we attempt to address this gap using a spatially explicit, individual‐based metacommunity model to explore the effects of landscape compositional heterogeneity and per se spatial configuration on diversity at the landscape and patch levels via their influence on long‐term community assembly processes. Our model simulates communities composed of species of annual, asexual organisms living, reproducing, dispersing, and competing within grid‐based, fractal landscapes that vary in their magnitude of spatial environmental heterogeneity and in their degree of spatial environmental autocorrelation. Communities are additionally subject to temporal environmental fluctuations and external immigration, allowing for turnover in community composition. We found that compositional heterogeneity and spatial autocorrelation had differing effects on richness, diversity, and the landscape and patch scales. Landscape‐level diversity was driven by community dissimilarity at the patch level and increased with greater heterogeneity, while landscape richness was largely the result of the short‐term accumulation of immigrants and decreased with greater compositional heterogeneity. Both richness and diversity decreased in variance with greater compositional heterogeneity, indicating a reduction in community turnover over time. Patch‐level richness and diversity patterns appeared to be driven by overall landscape richness and local mass effects, resulting in maximum patch‐level richness and diversity at moderate levels of compositional heterogeneity and high spatial autocorrelation.

Background and Aim: Inonotus obliquus (Ach. Ex. Pers), commonly known as Chaga, is a parasitic fungus that grows on birch trees. Indigenous North Americans and Northern Eurasians have used Chaga tea as a folk medicine for centuries, and there are currently significant interests in commercializing Chaga products, obtained either from conks (sclerotia) collected from nature or from laboratory cultured mycelia. The cultured mycelia's identity to date is based solely on chemical profiling and the morphologic characteristics; and genome identity are often overlooked and unreported in the literature. The aims of this study include: 1. To authenticate mycelium isolates derived from a Chaga sclerotium; 2. To determine Chaga sclerotium's bioactivities unreported previously. Experimental procedures: Identification of Chaga conk was carried out by chemical analyses, culture characteristics, and genome identity. The Chaga extracts’ bioactivities were evaluated via effects on cytokine and reactive oxygen species production on normal and cancer cell survival and proliferation. Results and Conclusion: The features of this mycelium isolate conformed to I. obliquus mycology, with > 99 % DNA sequence identity to the known GenBank Chaga Ribosomal Internal Spacer (ITS) sequence. Water extracts of Chaga were effective in protecting against oxidative stress in mouse neuroblastoma-spinal motor neuron NSC-34 cells and inhibited the proliferation of human brain glioblastoma DBTRG-05MG and pancreatic ductal adenocarcinoma PANC-1 cancer cell lines in vitro. In addition, the water extract potently stimulated inflammatory cytokines release from human blood cells, consistent with the biological response modifier features of mushroom beta- glucan polysaccharides.

In this work, palm-bunch enhanced stimulant (PES) was synthesized from palm bunch ashes (PBA), and applied in the optimized bioremediation of crude-oil laden water. Characterization of PBA revealed that the elemental composition composed sufficient constituents capable of propagating microbial driven biodegradation process. Gas column chromatography analysis of the raw and treated samples, confirmed that the residual sample contained only 82 lightweight hydrocarbon (HC) components as against 197 heavyweight hydrocarbon (HC) components contained in the untreated wastewater. Experimental design using response surface methodology (RSM) illustrated that PES concentration (F-value = 106.03) was the most significant process variable that influenced the bio-elimination of total petroleum hydrocarbon (TPH), while treatment time having an F-value of 4.56 exerted the least influence on the process. Mode appraisal analysis using error functions demonstrated that adaptive neuro-fuzzy inference system (ANFIS: R2 = 0.9725) modeling technique performed better than response surface methodology (RSM: R2 = 0.9480) in capturing the quadratic nature of the system. Particle swarm optimization tool (PSO) predicted an optimum TPH removal of 85.8% at PES conc. of 532 mg/L, 150 mg/L crude oil conc., pH value of 8.2, and treatment time of 3.4 days (81 hr., 36 min.). This optimum predicted value was validated using a set of triplicate experiments, and an average value of 85.2% TPH removal was obtained at the stipulated optimum process variables.

Abstract Metabolic disorders are often linked to alterations in insulin signaling. Omega-3 (n-3) fatty acids modulate immunometabolic responses; thus, we examined the effects of peripartum n-3 on systemic and adipose tissue (AT)-specific insulin sensitivity, immune function, and the endocannabinoid system (ECS) in dairy cows. Cows were supplemented peripartum with saturated fat (CTL) or flaxseed supplement rich in alpha-linolenic acid (ALA). Blood immunometabolic biomarkers were examined, and at 5–8 d postpartum (PP), an intravenous glucose-tolerance-test (GTT) and AT biopsies were performed. Insulin sensitivity in AT was assessed by phosphoproteomics and proteomics. Peripartum n-3 reduced the plasma concentrations of Interleukin-6 (IL-6) and IL-17α, lowered the percentage of white blood cells PP, and reduced inflammatory proteins in AT. Systemic insulin sensitivity was higher in ALA than in CTL. In AT, the top canonical pathways, according to the differential phosphoproteome in ALA, were protein-kinase-A signaling and insulin-receptor signaling; network analysis and immunoblots validated the lower phosphorylation of protein kinase B (Akt), and lower abundance of insulin receptor, together suggesting reduced insulin sensitivity in ALA AT. The n-3 reduced the plasma concentrations of ECS-associated ligands, and lowered the abundances of cannabinoid-1-receptor and monoglycerol-lipase in peripheral blood mononuclear cells PP. Peripartum ALA supplementation in dairy cows improved systemic insulin sensitivity and immune function, reduced ECS components, and had tissue-specific effects on insulin-sensitivity in AT, possibly counter-balancing the systemic responses.

This work proposed a model for the substrate treatment stage of biogas production process in an anaerobic digestion system. Adaptive neuro-fuzzy inference system (ANFIS), response surface method (RSM), and artificial neural network (ANN) were comparatively used in the simulation and modeling of the treatment process for improved biogas yield. Waste plantain peels were pretreated and used as substrate. FTIR and SEM results revealed that the pretreatment improved the substrate's desirable qualities. The amount of biogas yield was controlled by time, NaOH concentration, and temperature of the substrate pretreatment. Optimum pretreatment conditions obtained were a temperature of 102.7 °C, time of 31.7 min and NaOH concentration of 0.125 N. RSM, ANN, and ANFIS modeling techniques were proficient in simulating the biogas production, as evidenced by high R2values of 0.9281, 0.9850, and 0.9852, respectively. Furthermore, the values of the calculated error terms such as RMSE (RSM = 0.04799, ANN = 0.00969, and ANFIS = 0.00587) and HYBRID (RSM = 18.556, ANN = 0.803, and ANFIS = 0.0447) were low, indicating a satisfactory correlation between experimental and predicted values. Scrubbing of the biogas with caustic soda and activated charcoal increased the methane content to 94 %. The kinetics of the cumulative biogas yield were best fit with the Logistics and Modified Logistics models. The low C/N ratio in addition to the presence of potassium, nitrogen, and phosphorus suggested that the spent plantain peel slurry can be utilized as an agricultural fertilizer in crop production. The observations of this study therefore recommends the pre-treatment of biodigestion substrates as a key means to enhance beneficiation of methane production.

BackgroundTelemedicine-delivered medication for opioid use disorder (TMOUD) has become more prevalent during the COVID-19 pandemic, particularly in North America. This is considered a positive development as TMOUD has the potential to increase access to evidence-based treatment for a population heavily affected by the opioid crisis and consequent rising mortality and morbidity rates in relation to opioid use disorder. Despite the increase in the use of TMOUD, there are no established service- and process-focused models to guide the implementation of this intervention. ObjectiveThis study aims to develop a process- and service-focused implementation model in collaboration with key stakeholders and bring together peer-reviewed literature, practice-based knowledge, and expert opinions. MethodsThe simple rules for evidence translation in complex systems framework was applied to guide the development of a 6-step qualitative study. The steps were definition of the scope and objectives of the model, identification of evidence, stakeholder engagement, draft model development, key informant consultation, and final model specification. ResultsThe final specification for the TMOUD implementation model incorporated key strategic priorities, service delivery prerequisites, service design elements, stakeholder identification and engagement, key process domains, and iterative cycles of evaluation and improvement. ConclusionsThrough stakeholder engagement and key informant consultation, we produced a process- and service-focused TMOUD implementation model. The model is modifiable to different contexts and settings while also in keeping with the current evidence base and national and international standards of high-quality opioid use disorder care.

IntroductionIn today’s digital economy, data resources have gained strategic recognition. Enterprises view data analytic capabilities as a core organizational competitiveness. This study explored factors influencing college students’ continuance learning intention in data analysis technology courses to inform the role of self-efficacy on the relationship between interactivity and continuance learning intention.MethodsThe research model underpinning the study was based on the Stimulus-Organism-Response model and flow theory. The model was validated using SmartPLS. A total of 314 valid questionnaires were collected via the standard online survey approach.ResultsAmong internal factors, study results showed both cognitive interest and self-efficacy had significant positive effects on continuance learning intention. Also, cognitive interest had a significant positive effect on self-efficacy. Among external stimuli, content quality, software quality, and interactivity had significant positive effects on self-efficacy. Software quality did not have a significant effect on cognitive interest. Importantly, self-efficacy registered a significant moderating role on the relationship between interactivity and continuance learning intention.

Background: Effective treatment for human glioblastoma is lacking and a novel effective therapeutic agent is urgently needed. It is known that falcarinol-type polyacetylenes (FC-type PAs) are bioactive ingredients in ginseng and other plants from the Araliaceae family. Our earlier study showed that polyacetylene Falcarinol (FC), 1,2-dihydrofalcarinol (FCH) and 3-acetoxyfalcarinol (FCA) are potent proliferation inhibitors of human pancreatic ductal cancer cell lines. Methods: In this study we evaluated the bioactivities of these synthetic FC-type polyacetylenes (FC-type PAs) on human glioblastoma DBTRG-05MG cell line with cell viability, cell proliferation, cell migration, wound healing and clonogenic assays. We further evaluated synthetic FC on inhibition of DBTRG tumor bearing NOD-Prkdcem26Il2rgem26/Nju (NCG) mice. Results: FC dose dependently shifted DBTRG-05MG cells toward apoptosis as well as necrosis. FC and FCA, but not FCH, at near IC50 concentration inhibited colony formation in a 3-week clonogenic assay. Twice weekly intra-peritoneal injection of FC at 10 mg/kg significantly reduced tumor growth and tumor size compared to untreated control animals. Conclusions: Synthetic FC inhibits human glioblastoma cancer cell proliferation in vitro and in vivo. The availability of synthetic FC and other FC-type PAs in sufficient quantity and consistent quality would facilitate and expedite further research leading to potential clinical applications.

Abstract Background Dietary supplementation of omega-3 fatty acids can reduce the activation of the endocannabinoid system (ECS) by decreasing the availability of arachidonic acid, thus lowering endocannabinoids (eCBs) levels. The ECS is a modulator of energy metabolism, stress response and inflammation in mammals, yet there is little information on the roles of the ECS in transition dairy cows. During the periparturient period, the adipose tissue and liver are the main metabolic organs that participate in the adaptations of dairy cows to onset of lactation; however, exceeded adipose tissue lipolysis and accumulation of lipids in the liver have adverse effects on cows’ physiology. Here we aimed to examine whether omega-3 supplementation during the transition period will modulate ECS activation and affect metabolic and inflammatory indices in postpartum dairy cows, by supplementing twenty-eight transition Holstein dairy cows with either saturated fat (CTL) or encapsulated flaxseed oil (FLX). Components of the ECS, metabolic and inflammatory markers were measured in blood, liver, and subcutaneous adipose tissue. Results FLX supplementation reduced feed intake by 8.1% (P

IntroductionIt is essential to protect cancer patients from contracting COVID-19 through vaccination. A majority of cancer patients are recommended by international health authorities to take up the vaccines. COVID-19 vaccine refusal among cancer patients during the pandemic period is under-researched. This study investigated factors of vaccine refusal based on the Health Belief Model (HBM).MethodsA cross-sectional study was conducted among female breast cancer patients, male/female thyroid cancer patients, and gynecological cancer patients in Shantou, China from April to August 2022 (n = 1,115). Multinomial logistic regression analysis adjusted for socio-demographics was conducted to test factors of COVID-19. Adjusted odds ratios of the two models comparing vaccine refusal vs. “vaccine non-refusal” and vaccine refusal vs. ever-vaccination were derived and presented.ResultsOf all the participants, the prevalence of vaccine refusal, “vaccine non-refusal,” and ever-vaccination was 25.9, 22.2, and 51.8%, respectively. In both multinomial logistic regression models, significant factors of vaccine refusal included socio-demographics (age, education level, employment status, monthly household income, cancer type, duration since cancer diagnosis, current treatment status) and some vaccine-related HBM (perceived benefits, perceived barriers, cue to action, and self-efficacy). Perceived severity of COVID-19 was significant only in the vaccine refusal vs. ever-vaccination model. In neither model, perceived susceptibility to contract COVID-19 was statistically significant.ConclusionAbout ¼ of the participants expressed vaccine refusal. Interventions are warranted. Future longitudinal studies are needed to verify this study’s findings. Pilot interventions should also be launched to test effectiveness of interventions modifying the significant HBM factors found in this study.

To assess individual participants’ baseline thrombosis risk calculated by Caprini Risk Score (CRS) before injury, illness, or hospitalization occur, to increase the awareness of venous thromboembolism (VTE) by viewing 2 short videos. A cross-sectional study was conducted online between August 2022 and January 2023 in the USA, UK, and India to assess the risk of thrombosis of individuals as a baseline. One nursing practitioner and 4 high school students were on the research team. Descriptive statistical methods were used in data analysis. A total of 928 usable completed questionnaires from 945 participants were analyzed. The mean CRS was 4.93 ± 3.175; 0 to 4 (N = 460, 49.6%), 5 to 8 (N = 394, 42.5%), and 9 (N = 74: 8.0%). History of blood clots (N = 247, 26.6%),

BackgroundAccess to prescribed interventions and retention in treatment services are associated with improved health outcomes and reduced premature mortality rates for people living with opioid use disorder (OUD). In Leeds, transactional sex-workers frequently cycled in and out of treatment for OUD such that they never reached a level of engagement that permitted opportunities to meet their healthcare or housing needs. Barriers to accessing care provision include an itinerant lifestyle, difficulties with travel at unpredictable hours, impacting upon adherence to medication regimens including daily supervised consumption.ObjectivesTo use a co-produced, “health at the margins” approach, to reach the sex-working population in Leeds, and support informed choices about the potential to receive buprenorphine prolonged-release injection (BPRI) as a treatment option for OUD.MethodsBPRI was introduced using a theory of change model and improvements in sex-worker care delivery was reviewed. Strategies included buprenorphine micro-induction, shared decision-making, collaborative multi-agency working and supporting a strengths-based and trauma-informed approach.ResultsBenefits of BPRI included removal of the need for daily pharmacy visits, reducing the risk of diversion, improved medication adherence, stability and engagement with treatment and supportive services.ConclusionBPRI may offer an additional option for pharmacological interventions for people with OUD where there may be increased barriers to accessing treatment for example due to sex-working. Strategies for effective BPRI include micro-induction, shared decision-making, collaborative multi-agency working and supporting a strengths-based approach.

Summary: Molecular interactions between anorexigenic leptin and orexigenic endocannabinoids, although of great metabolic significance, are not well understood. We report here that hypothalamic STAT3 signaling in mice, initiated by physiological elevations of leptin, is diminished by agonists of the cannabinoid receptor 1 (CB1R). Measurement of STAT3 activation by semi-automated confocal microscopy in cultured neurons revealed that this CB1R-mediated inhibition requires both T cell protein tyrosine phosphatase (TC-PTP) and β-arrestin1 but is independent of changes in cAMP. Moreover, β-arrestin1 translocates to the nucleus upon CB1R activation and binds both STAT3 and TC-PTP. Consistently, CB1R activation failed to suppress leptin signaling in β-arrestin1 knockout mice in vivo, and in neural cells deficient in CB1R, β-arrestin1 or TC-PTP. Altogether, CB1R activation engages β-arrestin1 to coordinate the TC-PTP-mediated inhibition of the leptin-evoked neuronal STAT3 response. This mechanism may restrict the anorexigenic effects of leptin when hypothalamic endocannabinoid levels rise, as during fasting or in diet-induced obesity.

Background Coronavirus disease 2019 (COVID-19) vaccination is expected to end the pandemic; a high coverage rate is required to meet this end. This study aimed to investigate the prevalence of behavioral intention of free/self-paid COVID-19 vaccination and its associations with prosociality and social responsibility among university students in China. Methods An anonymous online cross-sectional survey was conducted among 6922 university students in five provinces in China during November 1-28, 2020. With informed consent, participants filled out an online survey link distributed to them via WeChat study groups. The response rate was 72.3%.Results The prevalence of behavioral intentions of free COVID-19 vaccination was 78.1%, but it dropped to 57.7% if the COVID-19 vaccination involved self-payment (400 RMB; around 42 USD). After adjusting for background factors, prosociality (free vaccination: adjusted odds ratio [ORa] = 1.10, 95% CI: 1.09-1.12; self-paid vaccination: ORa = 1.08, 95% CI: 1.07-1.09) and social responsibility (free vaccination: ORa = 1.17, 95% CI: 1.14-1.19; self-paid vaccination: ORa = 1.13, 95% CI: 1.11-1.14) were positively associated with the two variables of COVID-19 vaccination intention.Conclusion The present study demonstrated the positive effects of prosociality and social responsibility on the intention of COVID-19 vaccination. Accordingly, modification of prosociality and social responsibility can potentially improve COVID-19 vaccination. Future longitudinal and intervention studies are warranted to confirm such associations across populations and countries.

Abstract High-grade adsorbent (Fe–CS) was successfully synthesized from waste crab shells (CS) for the adsorptive removal of ammonia–nitrogen (A–N) from abattoir wastewater. Fe–CS was analyzed using Fourier transform infrared spectroscopy, x-ray diffraction, Scanning electron microscopy, and Thermogravimetric analysis. The characterization results indicated that Fe–CS possessed important qualities required for surface-driven chelation. The analysis of variance result showed that Fe–CS dosage (with f–value of 284.5) was the most effective process parameter of influence during A-N adsorption. The regression coefficients obtained from the process modeling illustrated the applicability of RSM (R 2 = 0.9799), ANN (R 2 = 0.9025), and ANFIS (R 2 = 0.9998) in predicting the A–N adsorptive removal, while the comparative statistical analysis established the superiority of ANFIS model over ANN and RSMs’ data prediction accuracy. The optimization result further demonstrated that ANFIS–GA predicted an optimum removal efficiency of 92.60% at pH of 6.5, a dosage of 2.2 g, A–N conc. of 18.8 mg/L, Temp. of 317 K, and adsorption time of 156 min. The mechanistic plot obtained from Weber–Morris model depicted that three regions were involved in the adsorption process. Boyd model parameters revealed that intraparticle diffusion controlled the process at low A–N concentration (A–N concentration ≤ 15 mg/L), while film diffusion dominated the adsorption process at concentrations higher than 15 mg/L. The average Gibbs free energy value ( $$- \Delta G^{0}$$ - Δ G 0 = 3.08212 kJ/mol), enthalpy ( $$\Delta H^{0}$$ Δ H 0 = 4.1150 kJ/mol), activation energy ( $$E_{A}$$ E A = 3.7454 kJ/mol) and entropy ( $$\Delta S^{0}$$ Δ S 0 = 22.9710 J/mol K) obtained from thermodynamic studies confirmed the spontaneous, endothermic, favorable and physical nature of the process.