Miracle-dz/UniFAR-FTUs huggingface dataset:
Projecting influenza vaccine effectiveness: A simulation study

The impact of influenza vaccination is largely measured by estimating vaccine effectiveness (VE), which vary in different seasons. Strain mutations and waning immunity present two key mechanisms affecting VE. We sought to quantify the relative effect of these mechanisms by projecting VE and the reduction of illness due to vaccination. We developed a stochastic age-structured agent-based simulation model of influenza transmission dynamics to encapsulate intraseason waning of immunity post-vaccination, and mutation-induced antigenic distance between circulating strains and vaccine strains. Parameterizing the model with published estimates, we projected the temporal and overall VE during an epidemic season, and estimated the reduction of infection for high (70%) and low (30%) vaccine efficacies to reflect the levels of vaccine-induced protection in randomized control trials. Both temporal and overall VE decreased as the attack rate increased, with lower median values for epidemics starting with strains that were antigenically more distant from vaccine strains. We observed a higher rate of temporal decline with considerably lower median values of the overall VE in the presence of intraseason waning of immunity compared with only the antigenic distance effect. The highest benefit of vaccination in preventing influenza infection was achieved at moderate attack rates in the range of 6%-15%. The results show that even when VE is relatively low in the population and almost negligible for older age groups (i.e., 50+ years), vaccination can still prevent significant illness in high-risk individuals; thereby reducing healthcare resource utilization and economic burden. Our study indicates that early vaccination remains an important strategy for alleviating the burden of seasonal influenza. Policy discussions on optimal timing of vaccination to reduce the effect of intraseason waning of immunity should be considered in the context of strain mutations within the epidemic course.
Exotic species drive patterns of plant species diversity in 93 restored tallgrass prairies.

A primary goal of restoration ecology is to understand the factors that generate variability in species diversity and composition among restorations. Plant communities may assemble deterministically towards a common community type, or they may assemble stochastically, ending differently because of weather conditions during establishment, soil legacy effects, or exotic species propagule pressure. To test these alternative hypotheses, we sampled plant communities and soil at 93 randomly selected restored prairies distributed throughout Iowa, USA. Five remnant sites were sampled as a reference. We tested our hypotheses using multiple regressions and investigated the strength of direct and indirect effects on species diversity and richness using structural equation models. The prairie restorations were highly variable in their age, size, diversity, soil characteristics, and how they were managed post-seeding. The strongest predictor of plant species richness and diversity was the degree of invasion, as measured by the abundance of exotic species. Restorations planted with species-rich seed mixes had reduced exotic species abundance, which led indirectly to higher species richness of restorations. Sites with higher organic matter and a more linear shape had a direct positive effect on exotic abundance, which in turn decreased diversity. We found little support for deterministic assembly, and diversity did not increase with the age of planting. Our results indicate that restored prairie communities tend to assemble into states of high or low diversity, driven by invasion from exotic plant species. Management of exotic species is essential for maximizing species diversity in temperate grassland restorations.
Nikkomycin Z—Ready to Meet the Promise?

Nikkomycin Z (NikZ) has fungicidal activity against some fungal species which currently requires patients to endure chronic therapy, sometimes for years. This review highlights reports of NikZ activity against fungal species for which current therapeutics are still inadequate, as a potential roadmap for continuing investigation. The possibility of faster and more complete clinical resolution by using NikZ has attracted scientific attention for decades. NikZ inhibits chitin structure formation, which is important for fungi, but not found in mammals. NikZ raised no safety concerns in a human Phase 1 trial or in extensive toxicology studies. NikZ showed strong clinical benefit in dogs with natural Coccidioides infection. NikZ has protected animals against fatal infections of Candida albicans. NikZ provides high protection in synergistic combination with several agent classes against Candida and Aspergillus species.
Evaluation of the effect of neutral electrolyzed water and peroxyacetic acid alone and in combination on microbiological, chemical, and sensory characteristics of poultry meat during refrigeration storage

The objectives of this study were to evaluate the efficacy of near-neutral electrolyzed water (NEW) (100 and 200 µg/ml), peroxyacetic acid (PAA) (200 and 400 µg/ml), and their combination (NEW 100 µg/ml + PAA 200 µg/ml) on microbial quality, pH, TBARS value, and sensory quality of fresh chicken breast meat dipped into the solutions for 10 min at room temperature. Meat samples were tested immediately after treatments and on days 2, 4, and 6 of storage at 4℃. All treatments were effective in reducing microbial populations throughout the storage (P < 0.05), with combined treatment showing the strongest antimicrobial activity. On the sixth day of storage, the aerobic plate counts, psychrophilic plate count, Enterobacteriaceae, lactic acid bacteria, and Pseudomonas counts in the NEW 100 µg/ml + PAA 200 µg/ml group were 1.33, 1.40, 1.45, 1.01, and 1.45 log CFU/g, respectively, which was lower than the control group (P < 0.05). In all treatments, the pH value of meat samples increased with storage time. During 6 days of storage, PAA400 group had the lowest increase in pH value (P < 0.05). On day 6, the combined treatment and PAA 400 µg/ml had the lowest lipid oxidation (P < 0.05). On day 6, the NEW100 + PAA200 group obtained the highest score in sensory attributes compared to other treatment groups (P < 0.05). According to the microbial and chemical analysis, the combined treatment of NEW and PAA can be a promising method to extend the shelf life of chicken by about 2 days at 4℃. Also, these compounds do not contain any harmful residues in chicken breast meat and their use is recommended in decontamination of poultry meat.
The Distinct Function and Localization of METTL3/METTL14 and METTL16 Enzymes in Cardiomyocytes

It has become evident that epitranscriptome events, mediated by specific enzymes, regulate gene expression and, subsequently, cell differentiation processes. We show that methyltransferase-like proteins METTL3/METTL14 and N6-adenosine methylation (m6A) in RNAs are homogeneously distributed in embryonic hearts, and histone deacetylase (HDAC) inhibitors valproic acid and Trichostatin A (TSA) up-regulate METTL3/METTL14 proteins. The levels of METTL3 in mouse adult hearts, isolated from male and female animals, were lower in the aorta and pulmonary trunks when compared with atria, but METT14 was up-regulated in the aorta and pulmonary trunk, in comparison with ventriculi. Aging caused METTL3 down-regulation in aorta and atria in male animals. Western blot analysis in differentiated mouse embryonic stem cells (mESCs), containing 10–30 percent of cardiomyocytes, showed METTL3/METTL14 down-regulation, while the differentiation-induced increased level of METTL16 was observed in both wild type (wt) and HDAC1 depleted (dn) cells. In parallel, experimental differentiation in especially HDAC1 wild type cells was accompanied by depletion of m6A in RNA. Immunofluorescence analysis of individual cells revealed the highest density of METTL3/METTL14 in α-actinin positive cardiomyocytes when compared with the other cells in the culture undergoing differentiation. In both wt and HDAC1 dn cells, the amount of METTL16 was also up-regulated in cardiomyocytes when compared to co-cultivated cells. Together, we showed that distinct anatomical regions of the mouse adult hearts are characterized by different levels of METTL3 and METTL14 proteins, which are changed during aging. Experimental cell differentiation was also accompanied by changes in METTL-like proteins and m6A in RNA; in particular, levels and distribution patterns of METTL3/METTL14 proteins were different from the same parameters studied in the case of the METTL16 protein.
Comparison of Videothoracoscopy and Thoracotomy in Surgical Treatment of Pulmonary Hydatid Cyst Disease.

OBJECTIVE To evaluate the outcomes of videothoracoscopic and open surgeries for pulmonary hydatid cysts. STUDY DESIGN Descriptive study. PLACE AND DURATION OF STUDY Department of Thoracic Surgery, Faculty of Medicine, Balıkesir University, Turkey, between May 2015 and March 2020. METHODOLOGY Patients who underwent surgery for pulmonary hydatid cysts were evaluated retrospectively, for the age, gender, symptoms, cyst size and localisation, preferred surgery, duration of surgery, the extent of the intraoperative bleeding, duration of the chest drainage, hospitalisation time, and postoperative complications. The relationship between the categorical variables was examined with the Chi-square and Fisher's exact tests and the relationship between the non-parametric data and continuous variables with the Mann-Whitney U-test. RESULTS A total of 60 patients included in the study; 23 underwent videothoracoscopic surgery and 37 had thoracotomy. There were no statistically significant differences between groups as gender, age, location and size of cyst. The videothoracoscopic surgery has superiority to thoracotomy group in terms of lower duration of operation, less perioperative bleeding (p = 0.005), early chest tube removal and lower hospitalisation time (both p <0.001). But there were no statistical difference between groups in complication rates (p = 0.340). CONCLUSION Videothoracoscopic removal of pulmonary hydatid cyst is a safe and advantageous procedure comparing to thoracotomy. There is a need for prospective studies with a larger sample size. Key Words: Hydatid cyst, Thoracoscopic surgery, Thoracotomy, VATS.
Recent Updates of Transarterial Chemoembolilzation in Hepatocellular Carcinoma

Transarterial chemoembolization (TACE) is a standard treatment for intermediate-stage hepatocellular carcinoma (HCC). In this review, we summarize recent updates on the use of TACE for HCC. TACE can be performed using two techniques; conventional TACE (cTACE) and drug-eluting beads using TACE (DEB-TACE). The anti-tumor effect of the two has been reported to be similar; however, DEB-TACE carries a higher risk of hepatic artery and biliary injuries and a relatively lower risk of post-procedural pain than cTACE. TACE can be used for early stage HCC if other curative treatments are not feasible or as a neoadjuvant treatment before liver transplantation. TACE can also be considered for selected patients with limited portal vein thrombosis and preserved liver function. When deciding to repeat TACE, the ART (Assessment for Retreatment with TACE) score and ABCR (AFP, BCLC, Child-Pugh, and Response) score can guide the decision process, and TACE refractoriness needs to be considered. Studies on the combination therapy of TACE with other treatment modalities, such as local ablation, radiation therapy, or systemic therapy, have been actively conducted and are still ongoing. Recently, new prognostic models, including analysis of the neutrophil-lymphocyte ratio, radiomics, and deep learning, have been developed to help predict survival after TACE.
Cancer Immunotherapy Dosing: A Pharmacokinetic/Pharmacodynamic Perspective

Immune check-point inhibitors are drugs that are markedly different from other anticancer drugs because of their indirect mechanisms of antitumoral action and their apparently random effect in terms of efficacy and toxicity. This marked pharmacodynamics variability in patients calls for reconsidering to what extent approved dosing used in clinical practice are optimal or whether they should require efforts for customization in outlier patients. To better understand whether or not dosing could be an actionable item in oncology, in this review, preclinical and clinical development of immune checkpoint inhibitors are described, particularly from the angle of dose finding studies. Other issues in connection with dosing issues are developed, such as the flat dosing alternative, the putative role therapeutic drug monitoring could play, the rise of combinatorial strategies, and pharmaco-economic aspects.
Fabrication and Performance Evaluation of the Helmholtz Resonator Inspired Acoustic Absorber Using Various Materials

A soundwave is transmitted by adjacent molecules in the medium, and depending on the type of sound, it exhibits various characteristics such as frequency, sound pressure, etc. If the acoustic wavelength of the soundwave is sufficiently long compared with the size of an acoustic element, physical analysis within the sound element could be simplified regardless of the shape of the acoustic element: this is called “long wavelength approximation”. A Helmholtz resonator, a representative acoustic element which satisfies the “long wavelength theory”, consists of a neck part and a cavity part. The Helmholtz resonators can absorb certain frequencies of sound through resonance. To exhibit attenuation properties at ultrasound range, the Helmholtz resonator should be made into a microscale since Helmholtz resonators should satisfy the “long wavelength approximation”. In this study, Helmholtz resonator inspired acoustic elements were fabricated using MEMS technology, and acoustic attenuation experiments in a water bath were conducted using various shapes and materials. As a result, the fabricated samples showed admirable attenuation properties up to ~13 dB mm−1 at 1 MHz. The results were analyzed to derive the necessary conditions for the fabrication of acoustic elements with acoustic attenuation properties in ultrasound range.
Properties of Macroalgae Biopolymer Films Reinforcement with Polysaccharide Microfibre

Developing robust and biodegradable biopolymer films based on macroalgae is a challenging task because of its inadequate mechanical strength and poor moisture barrier attribute to its hydrophilic nature. A promising and sustainable approach to overcome this challenge is to reinforce the biopolymer film with polysaccharide microfibre (microcrystalline cellulose) derived from Gigantochloa levis bamboo (GL-MCC). Eucheuma cottonii macroalgae were used for the development of biopolymer films without further extraction and purification, which was considered economical and easy. The mechanical, water contact angle (WCA), water absorption capacity (WSC), and thermal behaviour of macroalgae-based biopolymer films revealed that the inclusions of GL-MCC significantly enhanced the durability, moisture barrier, and thermal stability of the biopolymer films. The enhancement is ascribed to the interaction between macroalgae and GL-MCC due to high compatibility. Moreover, the incorporation of GL-MCC successfully increased the rigidity of the macroalgae-based biopolymer films against microorganism and moisture attack, but remain biodegradable and environmental-friendly. The developed biodegradable macroalgae/GL-MCC biopolymer films can potentially be used as packaging materials.
Lithium modulates miR‐1906 levels of mesenchymal stem cell‐derived extracellular vesicles contributing to poststroke neuroprotection by toll‐like receptor 4 regulation

Lithium is neuroprotective in preclinical stroke models. In addition to that, poststroke neuroregeneration is stimulated upon transplantation of mesenchymal stem cells (MSCs). Preconditioning of MSCs with lithium further enhances the neuroregenerative potential of MSCs, which act by secreting extracellular vesicles (EVs). The present work analyzed whether MSC preconditioning with lithium modifies EV secretion patterns, enhancing the therapeutic potential of such derived EVs (Li‐EVs) in comparison with EVs enriched from native MSCs. Indeed, Li‐EVs significantly enhanced the resistance of cultured astrocytes, microglia, and neurons against hypoxic injury when compared with controls and to native EV‐treated cells. Using a stroke mouse model, intravenous delivery of Li‐EVs increased neurological recovery and neuroregeneration for as long as 3 months in comparison with controls and EV‐treated mice, albeit the latter also showed significantly better behavioral test performance compared with controls. Preconditioning of MSCs with lithium also changed the secretion patterns for such EVs, modifying the contents of various miRNAs within these vesicles. As such, Li‐EVs displayed significantly increased levels of miR‐1906, which has been shown to be a new regulator of toll‐like receptor 4 (TLR4) signaling. Li‐EVs reduced posthypoxic and postischemic TLR4 abundance, resulting in an inhibition of the nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) signaling pathway, decreased proteasomal activity, and declined both inducible NO synthase and cyclooxygenase‐2 expression, all of which culminated in reduced levels of poststroke cerebral inflammation. Conclusively, the present study demonstrates, for the first time, an enhanced therapeutic potential of Li‐EVs compared with native EVs, interfering with a novel signaling pathway that yields both acute neuroprotection and enhanced neurological recovery.
Impacts of Multidrug-Resistant Pathogens and Inappropriate Initial Antibiotic Therapy on the Outcomes of Neonates with Ventilator-Associated Pneumonia

Abstract: Background It is unknown whether neonatal ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR) pathogens and inappropriate initial antibiotic treatment is associated with poor outcomes after adjusting for confounders. Methods: We prospectively observed all neonates with a definite diagnosis of VAP from a tertiary level neonatal intensive care unit (NICU) in Taiwan between October 2017 and March 2020. All clinical features, therapeutic interventions, and outcomes were compared between the MDR–VAP and non-MDR–VAP groups. Multivariate regression analyses were used to investigate independent risk factors for treatment failure. Results: Of 720 neonates who were intubated for more than 2 days, 184 had a total of 245 VAP episodes. The incidence rate of neonatal VAP was 10.1 episodes/per 1000 ventilator days. Ninety-six cases (39.2%) were caused by MDR pathogens. Neonates with MDR–VAP were more likely to receive inadequate initial antibiotic therapy (51.0% versus 4.7%; p < 0.001) and had delayed resolution of clinical symptoms (38.5% versus 25.5%; p = 0.034), although final treatment outcomes were comparable with the non-MDR–VAP group. Inappropriate initial antibiotic treatment was not significantly associated with worse outcomes. The VAP-attributable mortality rate and overall mortality rate of this cohort were 3.7% and 12.0%, respectively. Independent risk factors for treatment failure included presence of concurrent bacteremia (OR 4.83; 95% CI 2.03–11.51; p < 0.001), septic shock (OR 3.06; 95% CI 1.07–8.72; p = 0.037), neonates on high-frequency oscillatory ventilator (OR 4.10; 95% CI 1.70–9.88; p = 0.002), and underlying neurological sequelae (OR 3.35; 95% CI 1.47–7.67; p = 0.004). Conclusions: MDR–VAP accounted for 39.2% of all neonatal VAP in the neonatal intensive care unit (NICU), but neither inappropriate initial antibiotics nor MDR pathogens were associated with treatment failure. Neonatal VAP with concurrent bacteremia, septic shock, and underlying neurological sequelae were independently associated with final worse outcomes.
Opinion: To stop the next pandemic, we need to unravel the origins of COVID-19

We find ourselves ten months into one of the most catastrophic global health events of our lifetime and, disturbingly, we still do not know how it began. What’s even more troubling is that despite the critical importance of this question, efforts to investigate the origins of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and of the associated disease, coronavirus disease 2019 (COVID-19), have become mired in politics, poorly supported assumptions and assertions, and incomplete information. To avoid or mitigate the dire consequences of this and future pandemics (here, people in PPE bury a victim in Delhi, India in June), unraveling the origins of SARS-CoV-2 and COVID-19 will be essential—even though a definitive answer may be elusive, and an objective analysis means broaching some uncomfortable possibilities. Image credit: Shutterstock/PradeepGaurs. SARS-CoV-2 is a betacoronavirus whose apparent closest relatives, RaTG13 and RmYN02, are reported to have been collected from bats in 2013 and 2019, respectively, in Yunnan Province, China (1). COVID-19 was first reported in December 2019 more than 1,000 miles away in Wuhan City, Hubei Province, China. Beyond these facts, the “origin story” is missing many key details, including a plausible and suitably detailed recent evolutionary history of the virus, the identity and provenance of its most recent ancestors, and surprisingly, the place, time, and mechanism of transmission of the first human infection. Even though a definitive answer may not be forthcoming, and even though an objective analysis requires addressing some uncomfortable possibilities, it is crucial that we pursue this question. Preventing the next pandemic depends on understanding the origins of this one. There are several potential origin scenarios. First, SARS-CoV-2 may … [↵][1]1Email: relman{at}stanford.edu. [1]: #xref-corresp-1-1
Food Sources and Dietary Quality in Small Island Developing States: Development of Methods and Policy Relevant Novel Survey Data from the Pacific and Caribbean

Small Island Developing States (SIDS) have high and increasing rates of diet-related diseases. This situation is associated with a loss of food sovereignty and an increasing reliance on nutritionally poor food imports. A policy goal, therefore, is to improve local diets through improved local production of nutritious foods. Our aim in this study was to develop methods and collect preliminary data on the relationships between where people source their food, their socio-demographic characteristics and dietary quality in Fiji and Saint Vincent and the Grenadines (SVG) in order to inform further work towards this policy goal. We developed a toolkit of methods to collect individual-level data, including measures of dietary intake, food sources, socio-demographic and health indicators. Individuals aged ≥15 years were eligible to participate. From purposively sampled urban and rural areas, we recruited 186 individuals from 95 households in Fiji, and 147 individuals from 86 households in SVG. Descriptive statistics and multiple linear regression were used to investigate associations. The mean dietary diversity score, out of 10, was 3.7 (SD1.4) in Fiji and 3.8 (SD1.5) in SVG. In both settings, purchasing was the most common way of sourcing food. However, 68% (Fiji) and 45% (SVG) of participants regularly (>weekly) consumed their own produce, and 5% (Fiji) and 33% (SVG) regularly consumed borrowed/exchanged/bartered food. In regression models, independent positive associations with dietary diversity (DD) were: borrowing/exchanging/bartering food (β = 0.73 (0.21, 1.25)); age (0.01 (0.00, 0.03)); and greater than primary education (0.44 (0.06, 0.82)). DD was negatively associated with small shop purchasing (−0.52 (95% CIs −0.91, −0.12)) and rural residence (−0.46 (−0.92, 0.00)). The findings highlight associations between dietary diversity and food sources and indicate avenues for further research to inform policy actions aimed at improving local food production and diet.