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Abstract Therapeutic hypothermia is the standard treatment for hypoxic-ischemic encephalopathy (HIE), but despite its widespread use, the rates of mortality and neurodevelopmental impairment for moderate to severe HIE remain around 30%. Methylxanthines, such as caffeine and aminophylline, have potential neuroprotective effects in the setting of hypoxic-ischemic injury. However, data on the safety and efficacy of methylxanthines in the setting of therapeutic hypothermia for HIE are limited. This retrospective multicenter study examined in-hospital outcomes in 52 infants with HIE receiving methylxanthines and therapeutic hypothermia. The frequency of mortality and in-hospital morbidities were similar to those of infants enrolled in clinical trials undergoing therapeutic hypothermia without adjunctive therapies. Clinical trials of methylxanthines for neuroprotection in HIE are needed to determine safety and efficacy and should explore optimal dosing and timing of methylxanthine administration.

Abstract Background Since the introduction of combination antiretroviral therapy (cART) the brain has become an important human immunodeficiency virus (HIV) reservoir due to the relatively low penetration of many drugs utilized in cART into the central nervous system (CNS). Given the inherent limitations of directly assessing acute HIV infection in the brains of people living with HIV (PLWH), animal models, such as humanized mouse models, offer the most effective means of studying the effects of different viral strains and their impact on HIV infection in the CNS. To evaluate CNS pathology during HIV-1 infection in the humanized bone marrow/liver/thymus (BLT) mouse model, a histological analysis was conducted on five CNS regions, including the frontal cortex, hippocampus, striatum, cerebellum, and spinal cord, to delineate the neuronal (MAP2ab, NeuN) and neuroinflammatory (GFAP, Iba-1) changes induced by two viral strains after 2 weeks and 8 weeks post-infection. Results Findings reveal HIV-infected human cells in the brain of HIV-infected BLT mice, demonstrating HIV neuroinvasion. Further, both viral strains, HIV-1JR-CSF and HIV-1CH040, induced neuronal injury and astrogliosis across all CNS regions following HIV infection at both time points, as demonstrated by decreases in MAP2ab and increases in GFAP fluorescence signal, respectively. Importantly, infection with HIV-1JR-CSF had more prominent effects on neuronal health in specific CNS regions compared to HIV-1CH040 infection, with decreasing number of NeuN+ neurons, specifically in the frontal cortex. On the other hand, infection with HIV-1CH040 demonstrated more prominent effects on neuroinflammation, assessed by an increase in GFAP signal and/or an increase in number of Iba-1+ microglia, across CNS regions. Conclusion These findings demonstrate that CNS pathology is widespread during acute HIV infection. However, neuronal loss and the magnitude of neuroinflammation in the CNS is strain dependent indicating that strains of HIV cause differential CNS pathologies.

Cold temperature (≤20 ᵒC) storage or handling is required to maintain the quality characteristics of chocolate after production throughout the supply chain. The objective of this study was to assess the retail conditions, challenges, and willingness of retailers to use cooling devices. A total of 228 chocolate retailers sampled from Kumasi and Accra were interviewed using questionnaires with both closed and open-ended questions. The purposive, snowballing, and random sampling techniques were used. The collected data were analyzed using SPSS version 26. The majority of the respondents were female (82 %), aged between 21 and 30 years (33.9 %) and had a maximum of Junior High School education (39.0 %). About 15.4 % were registered retailers of Cocoa Processing Company - Ghana, 56.1 % sold on the streets of which 71.1 % sold under no shade and 71.9 % sold all day. A proportion of 76.2 % reported having challenges in their chocolate retail business. Among these challenges softening dominated with about 78.1 % of the retailers reported experiencing it in their daily operations. Spoilage (18.9 %), damage during handling (35.1 %), oily surface (34.2 %), darker surface appearance (10.1 %), and whitish surface appearance (39.9 %) were other challenges faced by retailers. The majority (76.8 %) of the respondents affirmed elevated temperatures caused melting, oil leakage and fat bloom in chocolate leading to rejections by clients. A significant proportion (81.1 %) indicated a cooling device for retail is necessary and were willing to use it when made available. The findings show that vending conditions were generally unsuitable for the shelf-stability of chocolates. An innovative vending device with cooling system would serve as possible intervention to mitigate the challenges faced by chocolate retailers.

Laminar flame codes have an important role in combustion modeling. They can provide a fundamental understanding of flame dynamics and provide a basis for building subgrid scale models in turbulent flow simulations. This paper presents Ignis, an open-source laminar flame code with the capability to offload submodels, like soot formation and radiation, using external packages and libraries. Ignis is written in C++, is documented with Doxygen, and is available on GitHub. It contains three different flame formulations: diffusion flames, premixed flames, and laminar flamelets solved in the mixture fraction coordinate. An option to facilitate creation of a diffusion flame table is also included. These options allow for Ignis to be used as a flame model for comparisons against experimental data, for use in turbulent subgrid models, or for flame structure investigations.

Chocolates sold in Ghana are stored under different conditions that are suspected to affect their appearance, flavour and texture. Rapid and non-invasive techniques such as near-infrared spectroscopy (NIRS) have been lauded for their reliability and cost-effectiveness that can be very useful for chocolate monitoring. This study developed a rapid and non-destructive method to predict the quality of chocolate obtained from three different sales outlets based on the location and conditions of retail. Data for physicochemical analysis (total color change, total phenolics, free fatty acid, peroxide value, moisture, hardness, and aluminum content) and mold count of chocolate were collected using standard protocols. These data and results obtained from NIRS in the wavelength range 900–1700 nm, were used to develop chemometric models to predict the parameters measured and classified the chocolate samples. Chocolate from the street recorded the highest mold count of 10.00 ± 18.92 cfu/g. Although the physicochemical analysis showed that different retail conditions had no significant effect on the chocolate quality parameters, the NIRS models could classify the chocolates based on retail conditions, with an average recognition and prediction accuracy of 75.41 % and 71.59 %, respectively. The regression model could predict the total color change with R2CV of 0.503 and RMSECV of 4.96 w/w. The findings suggest that NIRS combined with chemometrics could be used to classify chocolate sold under different conditions at different retail locations. However, the models could not predict other physicochemical quality parameters.

The contamination of edible agricultural goods with pesticides, including dichlorvos (DVDP), poses a substantial public health risk, promoting severe morbidity and mortality, especially in developing countries. It has been shown that hesperidin (hesperetin-7-O-rhamnoglucoside or Hes-7-RGlc) preserves cytomembrane, redox, and lipid homeostasis; unfortunately, its function on dichlorvos-incited heart damage has not been investigated. This work explored the ameliorative influence of Hes-7-RGlc on DVDP-activated cardiotoxicity. For this end, forty-two rats were randomly appropriated into seven groups (6 rats/group): Control, DVDP alone (8 mg.kg⁻¹day⁻¹), DVDP supplied with either Hes-7-RGlc (50 and 100 mg.kg⁻¹day⁻¹) or the reference medication atropine (0.2 mg.kg⁻¹day⁻¹), and Hes-7-RGlc alone (50 and 10 mg.kg⁻¹day⁻¹) were the seven groups investigated. DVDP was administered orally for seven days, followed by fourteen days of Hes-7-RGlc therapy. Then the rats were euthanized, and their blood and hearts were removed. Hes-7-RGlc chemotherapy substantially (p

Abstract Introduction Men with African ancestry have the highest incidence and mortality rates of prostate cancer (PCa) worldwide. Methods This study aimed to identify differentially methylated genes between tumor vs. adjacent normal and aggressive vs. indolent PCa in 121 African American patients. Epigenome‐wide DNA methylation patterns in tumor DNA were assessed using the human Illumina Methylation EPIC V1 array. Results Around 5,139 differentially methylated CpG‐sites (q 0.2) were identified when comparing normal vs. tumor, with an overall trend of hypermethylation in prostate tumors. Multiple representative differentially methylated regions (DMRs), including immune‐related genes, such as CD40, Galectin3, OX40L, and STING, were detected in prostate tumors when compared to adjacent normal tissues. Based on an epigenetic clock model, we observed that tumors’ total number of stem cell divisions and the stem cell division rate were significantly higher than adjacent normal tissues. Regarding PCa aggressiveness, 2,061 differentially methylated CpG‐sites (q .05) were identified when the grade group (GG)1 was compared with GG4/5. Among these 2,061 CpG sites, 155 probes were consistently significant in more than one comparison. Among these genes, several immune system genes, such as COL18A1, S100A2, ITGA4, HLA‐C, and ADCYAP1, have previously been linked to tumor progression in PCa. Conclusion Several differentially methylated genes involved in immune‐oncologic pathways associated with disease risk or aggressiveness were identified. In addition, 261 African American‐specific differentially methylated genes related to the risk of PCa were identified. These results can shedlight on potential mechanisms contributing to PCa disparities in the African American Population.

AbstractThe integration of health and activity data from various wearable devices into research studies presents technical and operational challenges. The Awesome Data Acquisition Method (ADAM) is a versatile, web-based system that was designed for integrating data from various sources and managing a large-scale multiphase research study. As a data collecting system, ADAM allows real-time data collection from wearable devices through the device’s application programmable interface and the mobile app’s adaptive real-time questionnaires. As a clinical trial management system, ADAM integrates clinical trial management processes and efficiently supports recruitment, screening, randomization, data tracking, data reporting, and data analysis during the entire research study process. We used a behavioral weight-loss intervention study (SMARTER trial) as a test case to evaluate the ADAM system. SMARTER was a randomized controlled trial that screened 1741 participants and enrolled 502 adults. As a result, the ADAM system was efficiently and successfully deployed to organize and manage the SMARTER trial. Moreover, with its versatile integration capability, the ADAM system made the necessary switch to fully remote assessments and tracking that are performed seamlessly and promptly when the COVID-19 pandemic ceased in-person contact. The remote-native features afforded by the ADAM system minimized the effects of the COVID-19 lockdown on the SMARTER trial. The success of SMARTER proved the comprehensiveness and efficiency of the ADAM system. Moreover, ADAM was designed to be generalizable and scalable to fit other studies with minimal editing, redevelopment, and customization. The ADAM system can benefit various behavioral interventions and different populations.

Summary: Male subfertility or infertility is a common condition often characterized by men producing a low number of sperm with poor quality. To gain insight into this condition, we performed a quantitative proteomic analysis of semen samples obtained from infertile and fertile men. At least 6 proteins showed significant differences in regulation of alternatively spliced isoforms. To investigate this link between aberrant alternative splicing and production of poor-quality spermatozoa, we overexpressed the hnrnpH/F-orthologue Glorund (Glo) in Drosophila, which was also found to be abundant in poor quality human sperm. Transgenic animals produced low numbers of morphologically defective spermatozoa and aberrant formation of the “dense body,” an organelle akin to the mammalian manchette. Furthermore, fertility trials demonstrated that transgenic flies were either completely infertile or highly subfertile. These findings suggest that dysregulation of hnrnpH/F is likely to result in the production of low-quality semen, leading to subfertility or infertility in men.

Abstract Theory in ethnobiology suggests that the selection of medicinal plants by local people in a given region is not random and evolutionary closely related species may have similar medicinal uses. Additionally, plants selection by local people is often driven by plant therapeutic efficacy, plant availability, plant versatility or local knowledge on medicinal plants. We tested the hypothesis of non‐random selection of medicinal plants as well as the potential mechanisms explaining such non‐random plants selection. We also tested for phylogenetic signal in medicinal plants. Our study was based in four villages across Benin, West Africa, where the local communities have deep knowledge about medicinal plants. We installed 91 plots around these four villages to establish the total list of plant species and their abundance. We then conducted ethnobotanical surveys in the same villages to identify medicinal plants used in the local pharmacopoeia. To test whether the selection of medicinal plants used in the region was non‐random and whether plant selection was driven by plant therapeutic efficacy, plant availability, plant versatility or local knowledge, we used a generalized linear model. Furthermore, we used the D‐statistic to test whether evolutionary closely related species are more commonly used as medicinal than other species. We found support for non‐random medicinal plant selection. Such a non‐random plant selection was driven by plant medicinal versatility. Plant availability and secondary compounds have no significant influence on plant selection. Local people's knowledge on medicinal plants was significantly affected by individuals' literacy but not by their gender, their age or the ethnic group they belong to. We found a weak phylogenetic signal in medicinal plant uses. Our study reveals that the most used families are not necessarily the ones that have more secondary compounds or that are the most available to the local people, but are the most versatile plants. The high level of medicinal flora used at the local scale, which contrasts with the country‐level analysis found by previous studies, suggests new methodological guidance in testing the theory of non‐random medicinal plants selection. Read the free Plain Language Summary for this article on the Journal blog.

Abstract Efforts to produce aromatic monomers through catalytic lignin depolymerization have historically focused on aryl–ether bond cleavage. A large fraction of aromatic monomers in lignin, however, are linked by various carbon–carbon (C–C) bonds that are more challenging to cleave and limit the yields of aromatic monomers from lignin depolymerization. Here, we report a catalytic autoxidation method to cleave C–C bonds in lignin-derived dimers and oligomers from pine and poplar. The method uses manganese and zirconium salts as catalysts in acetic acid and produces aromatic carboxylic acids as primary products. The mixtures of the oxygenated monomers are efficiently converted to cis,cis-muconic acid in an engineered strain of Pseudomonas putida KT2440 that conducts aromatic O-demethylation reactions at the 4-position. This work demonstrates that autoxidation of lignin with Mn and Zr offers a catalytic strategy to increase the yield of valuable aromatic monomers from lignin.

Through atomistic simulations, we uncover the dynamic properties of the Cantor alloy under shock-loading conditions and characterize its equation-of-state over a wide range of densities and pressures along with spall strength at ultra-high strain rates. Simulation results reveal the role of local phase transformations during the development of the shock wave on the alloy's high spall strength. The simulated shock Hugoniot results are in remarkable agreement with experimental data, validating the predictability of the model. These mechanistic insights along with the quantification of dynamical properties can drive further advancements in various applications of this class of alloys under extreme environments.

ABSTRACTAnnona muricata L. (soursop fruit) is a seasonal plant with bio-geographical distribution in tropical and subtropical climates. This study evaluated the proximate, phenolic, and antioxidant properties of different parts of soursop fruit. The influence of oven and solar drying on phenolic and antioxidant activities of extracts (pulp, seed, and peel) were assessed. Proximate analysis on different parts of the soursop fruit showed the pulp to have high carbohydrate (32.9% ± 0.3) and moisture (19.1% ± 1.0). The seeds however contained higher crude fat (37.5% ± 1.2) and protein (25.0% ± 0.1) contents. Total phenolic content of the seeds (8.7 mgGAE g−1 ± 0.1) was higher than that of the pulp and the peel (8.6 mgGAE g−1 ± 0.1). The solar-dried fruit parts demonstrated superior antioxidant activity to the oven-dried parts. Extracts from the solar-dried soursop fruit samples, especially the seed, can serve as useful therapeutic ingredient for diet supplementation and could also be exploited for its high oil and protein contents.

Abstract Background Neovascular age-related macular degeneration causes vision loss from destructive angiogenesis, termed choroidal neovascularization (CNV). Cx3cr1 −/− mice display alterations in non-classical monocytes and microglia with increased CNV size, suggesting that non-classical monocytes may inhibit CNV formation. NR4A1 is a transcription factor that is necessary for maturation of non-classical monocytes from classical monocytes. While Nr4a1 −/− mice are deficient in non-classical monocytes, results are confounded by macrophage hyper-activation. Nr4a1 se2/se2 mice lack a transcriptional activator, resulting in non-classical monocyte loss without macrophage hyper-activation. Main body We subjected Nr4a1 −/− and Nr4a1 se2/se2 mice to the laser-induced CNV model and performed multi-parameter flow cytometry. We found that both models lack non-classical monocytes, but only Nr4a1 −/− mice displayed increased CNV area. Additionally, CD11c+ macrophages were increased in Nr4a1 −/− mice. Single-cell transcriptomic analysis uncovered that CD11c+ macrophages were enriched from Nr4a1 −/− mice and expressed a pro-angiogenic transcriptomic profile that was disparate from prior reports of macrophage hyper-activation. Conclusions These results suggest that non-classical monocytes are dispensable during CNV, and NR4A1 deficiency results in increased recruitment of pro-angiogenic macrophages.

ABSTRACTThis study aimed to evaluate the physicochemical properties of okra residue obtained after pectin extraction from three okra genotypes (Asha, Balabi, and Agbagoma). The okra residue was oven-dried. Proximate analysis and functional properties were determined using standard AOAC methods, whereas mineral content was determined using atomic absorption spectroscopy. Phenolics and antioxidant capacity were determined using the Folin-Ciocalteu and DPPH methods. The okra pectin extraction residues were rich in carbohydrates (70.0–71.7%) and ash (19.55–21.9%), but had relatively low proteins (0.87–3.62%) and moisture (4.71–5.94%) contents. The okra residue samples had high potassium (8.59–9.27 mg/100 g) and sodium (.380–3.93 mg/100 g) contents. The solubility index for the varieties ranged from 18% to 25%, whiles swelling power ranged from 8% (Balabi) to 10% (Asha). The pectin extraction by-products showed high water absorption (546% to 617%) and oil absorption (216% to 318%) capacities. Residues from all okra genotypes demonstrated antioxidant activity (7.13–15.15%) and contained varied amounts of phenolic compounds (13.85–33.58 mg GAE/100 g). The results showed that okra residue obtained after pectin extraction has high nutritive and functional values, and could be exploited for other economic utilization instead of discarded as waste.

Competition for limited nest sites among secondary cavity-nesting bird species is intense and may result in loss of nests, physical conflict, injury, and occasionally death. The Prothonotary Warbler ( Protonotaria citrea ) is a secondary cavity-nesting species that has experienced a 38% population decline over the past five decades. In the northern portion of their range, Prothonotary Warblers are sympatric with two cavity-nesting species known for their nest usurpation behaviors: the House Wren ( Troglodytes aedon ) and Tree Swallow ( Tachycineta bicolor ). From 2017–2023 we monitored Prothonotary Warbler nests. House Wrens destroyed and usurped 38% of Prothonotary Warbler nests, which represented the greatest cause of nest failure, while Tree Swallows usurped only 1.5% of Prothonotary Warbler nests. We also documented two instances of adult Prothonotary Warblers likely killed by Tree Swallows. Interference competition from House Wrens is likely a significant factor limiting Prothonotary Warbler reproductive success where it is sympatric with these nest competitors.

The scope of this study was to apply advances in materials science, specifically the use of organosilicate nanoparticles as a high surface area platform for passive sampling of chemicals or pre-concentration for active sensing in multiple-phase complex environmental media. We have developed a novel nanoporous organosilicate (NPO) film as an extraction phase and proof of concept for application in adsorbing hydrophobic compounds in water and sediment. We characterized the NPO film properties and provided optimization for synthesis and coatings in order to apply the technology in environmental media. NPO films in this study had a very high surface area, up to 1325 m2/g due to the high level of mesoporosity in the film. The potential application of the NPO film as a sorbent phase for sensors or passive samplers was evaluated using a model hydrophobic chemical, polychlorinated biphenyls (PCB), in water and sediment. Sorption of PCB to this porous high surface area nanoparticle platform was highly correlated with the bioavailable fraction of PCB measured using whole sediment chemistry, porewater chemistry determined by solid-phase microextraction fiber methods, and the Lumbriculus variegatus bioaccumulation bioassay. The surface-modified NPO films in this study were found to highly sorb chemicals with a log octanol-water partition coefficient (Kow) greater than four; however, surface modification of these particles would be required for application to other chemicals.

Pentadesma butyracea seed butter or fat (PBSB) is a vegetable fat extracted from the seeds of the P. butyracea plant. The butter has potential use in the food, pharmaceutical, and cosmetic industries. The study investigated traditional PBSB processing methods in Ghana and evaluated their effects on yield, physicochemical parameters, and fatty acid composition. Four traditional extraction methods were identified and evaluated, and these methods are direct wet extraction of PBSB from a fresh mixture of the seed paste and water (DEW); wet extraction of PBSB from a 12-hour fermented mixture of the seed paste and water (FWO); direct wet extraction of PBSB from a fresh mixture of the seed paste, salt, and water (DES); and wet extraction of PBSB from a 12-hour fermented mixture of the seed paste, salt, and water (FSO). Results of physicochemical properties of the PBSB samples showed moisture content of 0.06-0.07%, free fatty acid of 1.38-2.43%, iodine value of 56.50-56.85 Wijs, peroxide value of 5.58-8.52 mEq/kg, relative density of 0.91, refractive index of 1.462-1.464, percent impurities of 0.015-0.017%, saponification value of 165.57-178.02 mg KOH/g, and percent unsaponifiable matter of 2.60-3.18%. The PBSB yield varied in the range of 21.68-26.97%, with the highest average butter yield observed for FWO. Seventeen fatty acids were characterized in the PBSB samples, and they included ten saturated fatty acids, five monounsaturated fatty acids, and two polyunsaturated fatty acids. Key fatty acids found in the PBSB samples were oleic acid (51.21-51.31%), stearic acid (43.22-43.33%), palmitic acid (2.91-3.07%), linoleic acid (0.49-0.51%), linolenic acid (0.12-0.20%), and arachidic acid (0.14-0.15%). PBSB samples produced by the various traditional extraction methods in Ghana recorded similar physicochemical characteristics as unrefined shea butter per the Regional Standard for Unrefined Shea Butter (CXS 325R-2017) as well as Cook Brand Margarine, a common commercial baking fat, and thus, their potential food application such as an alternative shortening/ingredient could be explored in a future study.

Cucurbita pepo L., Citrullus lanatus T. and Cucumis melo L. belong to the family Cucurbitaceae and are cultivated for their seeds. The fruit pulp and peel are discarded as agro-waste after seed removal. This study evaluated the physicochemical and functional properties of the pulp and pectin extracts from the Cucurbitaceae species. Proximate, antioxidant, total polyphenol and flavonoid contents were determined. The purity, structural and sugar constituents of the extracted pectin were analysed using spectrophotometric techniques (NMR, FTIR and LCMS). Results showed that the pulp wastes had high carbohydrate content (28.4 to 69.7%) and demonstrated high antioxidant activities (40 to 50%, 63 to 85% and 0.2 to 0.4 mg mL−1 for DPPH, ABTS and FRAP respectively). Cucurbita pepo L. had the highest pectin yield (13.9%), and the purity of the pectin extracts ranged from 60.4 to 75.2% for total carbohydrate and 3.3 to 4.4 % for protein. The pectin extracts showed structural similarities. LCMS fingerprints of the pectin extracts showed that the monosaccharides comprised of mannose, rhamnose, galacturonic acid, glucose, galactose, xylose, arabinose and fucose. The polymers demonstrated high water absorption capacities (309 g/100 g to 604 g/100 g) and can be applied as thickeners in food systems.

Pectin extractable from okra (Abelmoschus esculentus L.) is known to have various food and non-food applications. The objective of this work was to investigate the effect of particle size of milled samples on okra pectin yield using two different extraction solvents. Phosphate buffer (PB) and citric acid solution (CAS) (at pH 6, temperature of 80°C and for 1 h) were used to extract pectin from 10 g of milled okra sample with varying particle sizes (0.5, 1 and 2 mm). Ethanol was added to the aqueous extract to precipitate the pectin. The crude pectin obtained was then freeze-dried and the % pectin yield was calculated. The average okra pectin yield when PB was used for extraction were 19.6±4.0%, 15.8±1.0% and 11.9±1.5% for 0.5 mm, 1 mm and 2 mm particle sizes, whereas that of the CAS counterparts were 32.7±8.1%, 25.6±0.8% and 35.6±5.5%, respectively. However, considering purity of the pectin extracts (PB > CAS), the present findings indicated that a higher pectin yield is achievable with 0.5 mm as the optimal particle size of okra pod powder using phosphate buffer as extraction solvent.

Secondary plant cell walls are composed of carbohydrate and lignin polymers, and collectively represent a significant renewable resource. Leveraging these resources depends in part on a mechanistic understanding for diffusive processes within plant cell walls. Common wood protection treatments and biomass conversion processes to create biorefinery feedstocks feature ion or solvent diffusion within the cell wall. X-ray fluorescence microscopy experiments have determined that ionic diffusion rates are dependent on cell wall hydration as well as the ionic species through non-linear relationships. In this work, we use classical molecular dynamics simulations to map the diffusion behavior of different plant cell wall components (cellulose, hemicellulose, lignin), ions (Na+, K+, Cu2+, Cl−) and water within a model for an intact plant cell wall at various hydration states (3–30 wt% water). From these simulations, we analyze the contacts between different plant cell wall components with each other and their interaction with the ions. Generally, diffusion increases with increasing hydration, with lignin and hemicellulose components increasing diffusion by an order of magnitude over the tested hydration range. Ion diffusion depends on charge. Positively charged cations preferentially interact with hemicellulose components, which include negatively charged carboxylates. As a result, positive ions diffuse more slowly than negatively charged ions. Measured diffusion coefficients are largely observed to best fit piecewise linear trends, with an inflection point between 10 and 15% hydration. These observations shed light onto the molecular mechanisms for diffusive processes within secondary plant cell walls at atomic resolution.

Abstract Background Cholera, a diarrheal disease caused by the bacterium Vibrio cholerae, transmitted through fecal contamination of water or food remains an ever-present risk in many countries, especially where water supply, sanitation, food safety, and hygiene are inadequate. A cholera outbreak was reported in Bauchi State, North-eastern Nigeria. We investigated the outbreak to determine the extent and assess risk factors associated with the outbreak. Methods We conducted a descriptive analysis of suspected cholera cases to determine the fatality rate (CFR), attack rate (AR), and trends/patterns of the outbreak. We also conducted a 1:2 unmatched case–control study to assess risk factors amongst 110 confirmed cases and 220 uninfected individuals (controls). We defined a suspected case as any person > 5 years with acute watery diarrhea with/without vomiting; a confirmed case as any suspected case in which there was laboratory isolation of Vibrio cholerae O1 or O139 from the stool while control was any uninfected individual with close contact (same household) with a confirmed case. Children under 5 were not included in the case definition however, samples from this age group were collected where such symptoms had occurred and line-listed separately. Data were collected with an interviewer-administered questionnaire and analyzed using Epi-info and Microsoft excel for frequencies, proportions, bivariate and multivariate analysis at a 95% confidence interval. Results A total of 9725 cases were line-listed with a CFR of 0.3% in the state. Dass LGA had the highest CFR (14.3%) while Bauchi LGA recorded the highest AR of 1,830 cases per 100,000 persons. Factors significantly associated with cholera infection were attending social gatherings (aOR = 2.04, 95% CI = 1.16–3.59) and drinking unsafe water (aOR = 1.74, 95% CI = 1.07–2.83). Conclusion Attending social gatherings and drinking unsafe water were risk factors for cholera infection. Public health actions included chlorination of wells and distribution of water guard (1% chlorine solution) bottles to households and public education on cholera prevention. We recommend the provision of safe drinking water by the government as well as improved sanitary and hygienic conditions for citizens of the state.

Background: DNA methylation-based measures of biological aging have been associated with air pollution and may link pollutant exposures to aging-related health outcomes. However, evidence is inconsistent and there is little information for Black women. Objective: We examined associations of ambient particulate matter

Rationale & Objective: Patients with chronic kidney disease (CKD) not receiving dialysis, including kidney transplant recipients, often experience difficulties regarding self-management. An important barrier for adherence to self-management recommendations may be the presence of psychological distress, consisting of depressive and anxiety symptoms. We investigated relationships between psychological distress and adherence to self-management recommendations. Study Design: Cross-sectional online questionnaire data as part of the E-GOAL study. Setting & Participants: Patients with CKD (estimated glomerular filtration rate, 20-89 mL/min/1.73 m2) were recruited from April 2018 to October 2020 at 4 hospitals in The Netherlands and completed online screening questionnaires. Exposures: Psychological distress, depressive symptoms, and anxiety symptoms. Outcomes: Dietary adherence, physical activity, medication adherence, smoking, body mass index, and a CKD self-management index (ie, the sum of 5 binary indicators of nonadherence to the recommended self-management factors). Analytical Approach: Adjusted multivariable regression and ordinal logistic regression analyses. Results: In our sample (N = 460), 27.2% of patients reported psychological distress, and 69.8% were nonadherent to 1 or more recommendations. Higher psychological distress was significantly associated with poorer dietary adherence (βadj, −0.13; 95% CI, −0.23 to −0.04), less physical activity (βadj, −0.13; 95% CI, −0.22 to −0.03), and lower medication adherence (βadj, −0.15; 95% CI, −0.24 to −0.05), but not with smoking and body mass index. Findings were similar for depressive symptoms, whereas anxiety was only associated with poorer dietary and medication adherence. Every 1-point higher psychological distress was also associated with a higher likelihood of being nonadherent to an accumulating number of different recommendations (adjusted OR, 1.04; 95% CI, 1.02-1.07). Limitations: Cross-sectional design, possible residual confounding, and self-report. Conclusions: Many people with CKD experience psychological distress, of whom most have difficulties self-managing their CKD. Given the relationship between psychological distress and adherence to CKD self-management recommendations, behavioral interventions are needed to identify and treat psychological distress as a potential barrier to CKD self-management. Plain-Language Summary: This online questionnaire study investigated relationships between psychological distress and self-management among 460 people with chronic kidney disease. Over a quarter of them reported mild-to-severe psychological distress. Alarmingly, 4 out of 5 patients with psychological distress were also nonadherent to 1 or more self-management recommendations, and higher levels of psychological distress were associated with poorer dietary and medication adherence and lower physical activity. Moreover, patients who suffered from moderate-to-severe distress were relatively more often nonadherent to 3 or more recommendations compared with patients with no or mild distress symptoms. So, it seems that psychological distress can be a barrier for self-management. To support patients in managing chronic kidney disease, researchers and health professionals should not overlook patients’ mental health.

Edible mushrooms commonly found in forest reserves are important for food security but they are underutilized in Ghana. The Atewa forest reserve in the Eastern Region and Bia Biosphere in the Western Region are among the largest forest reserves in Ghana. However, human activities including illegal mining activities pose a threat to the existence of the rich mushroom diversity within these forests. The objective of this study, therefore, was to collect, characterize and domesticate mushrooms from the Atewa forest reserve and the Bia Biosphere. Wild mushroom samples were randomly photographed, collected, dried and stored. Edible and wild mushrooms were characterized morphologically and compared with literature. A total of 86 mushroom samples (comprising 45 from the Atewa forest reserve and 41 from the Bia Biosphere) were collected and identified. The two forest reserves contained a rich diversity of wild mushrooms namely: Cookeina speciosa, Marasmiellua inoderma, Auricularia cornea, Daldina concentrica, Pleurotus sp. Polypores. Cultivated Auricularia auricula strain AUAT recorded the highest ash content (16.70%) while cultivated Ganoderma sp. strain GLB recorded the lowest ash content (5.12%). On the other hand, cultivated Pleurotus ostreatus strain POB recorded the highest fat content of 19.88% and cultivated Pleurotus saju-caju strain PSCAT gave the least value of 12.02%. Cultivated Auricularia auricula strain AUAT again recorded the highest protein value of 33.38% while wild Ganoderma sp. Strain GLB had the least protein value. A total carbohydrate level of 64.22% was observed in cultivated Ganderma sp. strain GLB. The highest oxalate content of 30.93 mg/100 g was recorded in cultivated Pleurotus ostreatus strain EM1 with cultivated Auricularia auricula strain AUAT being the least value of 4.73 mg. A high phytate value of 149.35 mg was observed in cultivated Auricularia auricula strain AUAT and cultivated Pleurotus saju-caju strain PLAT showed the lowest value of 31.60 mg/100 g. The present findings provide considerable data on fungal diversification, conservation and domestication as well as a reference point for future studies.

This study ascertained the indigenous knowledge and uses of Pentadesma butyracea plant through a focus group study. The proximate, mineral, antinutritional compositions, and antioxidant activity of P. butyracea seed were also determined using standard analytical methods. The results of the focus group study showed that P. butyracea is essentially used for its butter which is prepared by women processors who hand down the skill of butter processing to their children. The butter is used for cooking, frying, and preparing traditional delicacies, and the plant is known to possess some therapeutic potential. The seed recorded the following mean proximate values: fat content of 35.82%, carbohydrate of 50.97%, 1.81% ash, 2.68% protein, 1.34% crude fibre, and moisture of 7.39%. The most abundant mineral in the seed is potassium (32.93 mg/100 g). Calcium, magnesium, phosphorus, sodium, iron, and zinc were at levels of

Abstract Background Commensal Escherichia coli residing in the guts of humans and animals are reservoirs of multidrug resistance (MDR) genes, including quinolone resistance genes, in humans and poultry. This study aimed to characterize quinolones resistance in E. coli recovered from poultry workers, chickens, and poultry farm/market environments in Abuja, Nigeria. Methods This was a cross-sectional study conducted between December 2018 and April 2019 comprising poultry workers, chickens and their poultry farm/market environments. This study characterized E. coli isolates from stool, faecal and environmental samples using antimicrobial susceptibility testing and whole-genome sequencing methods. Core-genome multilocus sequences-based phylogeny was used to determine the relatedness between quinolone-resistant E. coli isolates. Data were analyzed using descriptive statistics. Results Of 110 E. coli isolates, quinolone-resistant phenotypes were observed in 68.2% (n = 75) isolates. Whole-genome sequencing detected plasmid-mediated quinolone resistance (PMQR) genes in 63.6% (n = 70) isolates. The most prevalent PMQR gene detected in 56 of these 70 E. coli isolates was qnrS1, followed by qnrB19 in 14 isolates and aac(6’)-lb-cr in two isolates. Fifteen ciprofloxacin and 19 nalidixic acid-resistant isolates respectively showed double mutations in the quinolone-resistance determining regions (QRDRs) of gyrA, with single or double mutations in parC, and a single mutation in parE. The most prevalent amino-acid substitutions observed were S83L + D87N in gyrA (46.5%, n = 20), S80I in parC (51.2%, n = 22) and S458A in parE (14%, n = 6). About 2.9% (2/70) of PMQR isolates were extended-spectrum beta-lactamase (ESBL) producers while 2.9% (2/70) had plasmid-mediated colistin resistance (PMCR) genes. Conclusions PMQR genes were prevalent in E. coli isolates recovered from healthy humans, chickens and poultry farm/market environments. PMCR genes (mcr-1.1) occurred in PMQR-positive isolates recovered from manure and drinking water originating from poultry farm/market environments. It was found that the gene encoding ESBL coexisted with qnrS-positive isolates of human and avian origin. Horizontal transfer of PMQR genes among E. coli isolates in the human-poultry-environment interface has public health implications for the spread of antimicrobial resistance. Relevant government agencies should enforce regulations to restrict the use of critically important antimicrobials in poultry production.

Salmonella is a ubiquitous organism of public health importance that causes diarrhea and other systemic disease syndromes. The ecology and epidemiology of the organism in addition to the roles played by wild animals are important in understanding its disease. Relevant published peer-reviewed literature was obtained after imputing the study's keywords into the Google search engine. The publications were thereafter saved for the study. The study revealed the ecology of Salmonella is directly related to its epidemiology. These were found to be either positively or negatively influenced by the living and non-living parts of the environment. Free-ranging and captive wild animals can serve as asymptomatic carriers of Salmonella, therefore, help to maintain the cycle of the disease since wildlife serves as reservoir hosts to over 70% of emerging zoonotic diseases. Cockroaches transmit Salmonella through their feces, and body parts and when ingested by birds and animals. The statistically significant over 83% of Salmonella isolation in lizards suggests the reptile could be a source of Salmonella distribution. Snakes, foxes, badgers, rodents, and raccoons have been reported to have Salmonella as a natural component of their gut with the ability to shed the organism often. The high occurrence (>45%) of diverse Salmonella serovars coupled with the fact that some of these animals were handled, kept as pets and consumed by man portends these animals as potential sources of transmission of the organism and the disease. The etiology and epidemiology of Salmonella are overtly affected by several environmental factors which also determine their survival and maintenance. The roles played by wild animals in the relationship, transmission, growth or interaction within and between Salmonella spp., the occurrence, prevalence, and distribution of the organism help maintain the organism in the environment. An understanding of the roles played by the different parts of the environment and wild animals in the ecology and epidemiology of Salmonella can help make informed decisions on the prevention and control of the diseases it causes. This review aimed to investigate the relationship between ecology, epidemiology, and environment, including the roles played by wild animals in the maintenance of the organism and its disease.

Context: Anterior craniocervical junction lesions have always been a challenge for neurosurgeons. Presenting with lower cranial nerve dysfunction and symptoms of brainstem compression, decompression is often required. While posterior approaches offer indirect ventral brainstem decompression, direct decompression via odontoidectomy is necessary when they fail. The transoral and endoscopic endonasal approaches have been explored but come with their own limitations and risks. A novel retropharyngeal approach to the cervical spine has shown promising results with reduced complications. Aims: This study aims to explore the feasibility and potential advantages of the anterior retropharyngeal approach for accessing the odontoid process. Methods and Surgical Technique: To investigate the anatomical aspects of the anterior retropharyngeal approach, a paramedian skin incision was performed below the submandibular gland on two cadaveric specimens. The subcutaneous tissue followed by the platysma is dissected, and the superficial fascial layer is opened. The plane between the vascular sheath laterally and the pharyngeal structures medially is entered below the branching point of the facial vein and internal jugular vein. After reaching the prevertebral plane, further dissection cranially is done in a blunt fashion below the superior pharyngeal nerve and artery. Various anatomical aspects were highlighted during this approach. Results: The anterior, submandibular retropharyngeal approach to the cervical spine was performed successfully on two cadavers highlighting relevant anatomical structures, including the carotid artery and the glossopharyngeal, hypoglossal, and vagus nerves. This approach offered wide exposure, avoidance of oropharyngeal contamination, and potential benefit in repairing cerebrospinal fluid fistulas. Conclusions: For accessing the craniocervical junction, the anterior retropharyngeal approach is a viable technique that offers many advantages. However, when employing this approach, surgeons must have adequate anatomical knowledge and technical proficiency to ensure better outcomes. Further studies are needed to enhance our anatomical variations understanding and reduce intraoperative risks.

The complementarity of acids and bases is a fundamental chemical concept. Here, the authors use simple acid-base chemistry to encode binary information and perform information processing including digital circuits and neural networks using robotic fluid handling.

The texture of yams is a key determinant in the selection of yams for boiled and pounded yams. This study was conducted to quantify pectin from local and newly developed yam varieties and to correlate pectin and its degree of esterification (DE) with instrumental textural profile parameters of boiled and pounded yam. Isolation of pectin from yam cell wall material (CWM) was achieved with citric acid and the degree of esterification (DE) was determined. The textural parameters were obtained using a texture analyzer. All the new D. rotundata (Poir) varieties had low CWM which varied from 11.88 to 18.95% compared to the D. alata varieties which ranged from 27.60 to 32.79%. Pectin yield (%) for CRI D. alata varieties ranged from 4.47 to 11.35 while CRI D. rotundata (Poir) varieties ranged from 5.18 to 5.50%. Generally, CRI D. alata yam varieties had higher pectin than D. rotundata (Poir) varieties. The DE for all samples ranged from 22.54 to 51.37%, making yam pectin low methoxy. Positive correlations existed between the textural parameters and pectin content as well as the DE but were not significant (p > .05). This study shows that low methoxy yam pectin has no effect on textural characteristics of boiled and pounded yam.

Some new cassava accessions have been developed and released because of their high yield, resistance to disease, adaptability to wider ecological environment, and less cost of production. However, their flour and starch properties have not been characterized for potential food applications. In the present study, starch and flour were produced from two new cassava accessions (Sika Bankye and Bankye Hemaa) and evaluated for their physicochemical and pasting properties. The flour samples recorded higher values for the various functional parameters compared to their starch counterparts. Both flour samples had a similar water absorption capacity (WAC) of ~263% but the associated starch from Bankye Hemaa recorded the lowest value of 38.6%. Bankye Hemaa flour recorded the highest oil absorption capacity (OAC) (121%) and could be exploited as potential flavor retainer in products. Flour from Bankye Hemaa also recorded the highest swelling power (882 ± 29%), which was indicative of their good thickening and stabilizing functionalities. Sika Bankye starch had the highest setback viscosity (723 ± 32 RVU), which was indicative of its lower susceptibility to retrogradation and potential use in products that require highly viscous paste and processed at high temperatures.

The potential uses of starches and flours depend on their physicochemical and functional properties. The chemical composition, functional and pasting properties of starch and flours obtained from some newly developed yam varieties from the Crops Research Institute (CRI), Ghana were evaluated, and compared with the existing local varieties. The results showed that the physicochemical and functional properties varied among the varieties studied. The CRI varieties were grouped in a principal component analysis as moisture (afase pa), amylose content (ahodenfo, soanyinto, afase biri), high starch content, bulk density and water absorption capacity (kukrupa, Mankrong pona, CRI pona). Starch pasting characteristics showed that Mankrong pona, CRI pona and afase pa exhibited stable pastes whereas afase biri, Mankrong pona and, afase soanyinto could be utilized for high-temperature processing. Overall, the new CRI varieties showed considerable functionalities that could be explored for potential food and industrial applications as compared to the existing local varieties.

Rain tree pod (RTP) has the potential to contribute to food security, but it is underutilized in Ghana. In this study, the physicochemical, mineral, functional, and pasting properties of RTP flour as a composite with wheat flour at different inclusion levels (5–30%) were evaluated. The moisture, crude protein, ash, crude fat, crude fiber, and carbohydrate were in the range of 8.3–9.2%, 12.3–14.89%, 0.80–1.42%,1.25–1.45%, 0.32–1.35%, and 72.13–75.47%, respectively. The composite flours had considerable mineral content (Ca, Mg, Na, and P) with K (807–1153 mg/100 g) being the most abundant, but K and Na were improved in the composite flour T3 (15%). The composite flours had varied bulk densities with Hausner’s ratio in the range 1.32–1.59, 4.47–6.72% foaming capacity, 86.32–96.61% foaming stability, 9.09–15.44% solubility, 6.3–6.96% swelling power, 137.4–63.8% oil absorption capacity, and 149.74-202.97% water absorption capacity. The pasting properties of the composite flour samples ranged from 9.87 to 11.07 min peak time, 50.7–90.83°C pasting temperature, 555.0–1527.0 RVU peak viscosity, 384.0–1004.5 RVU trough viscosity, 95–768RVU breakdown viscosity, 150.0–371 setback viscosity, and 600.0–1141.0 RVU final viscosity. Overall, the findings showed that the RTP-wheat composite flours had appreciable nutrient and functional properties that could be exploited in potential food formulations.

Abstract Early detection of severe asthma exacerbations through home monitoring data in patients with stable mild-to-moderate chronic asthma could help to timely adjust medication. We evaluated the potential of machine learning methods compared to a clinical rule and logistic regression to predict severe exacerbations. We used daily home monitoring data from two studies in asthma patients (development: n = 165 and validation: n = 101 patients). Two ML models (XGBoost, one class SVM) and a logistic regression model provided predictions based on peak expiratory flow and asthma symptoms. These models were compared with an asthma action plan rule. Severe exacerbations occurred in 0.2% of all daily measurements in the development (154/92,787 days) and validation cohorts (94/40,185 days). The AUC of the best performing XGBoost was 0.85 (0.82–0.87) and 0.88 (0.86–0.90) for logistic regression in the validation cohort. The XGBoost model provided overly extreme risk estimates, whereas the logistic regression underestimated predicted risks. Sensitivity and specificity were better overall for XGBoost and logistic regression compared to one class SVM and the clinical rule. We conclude that ML models did not beat logistic regression in predicting short-term severe asthma exacerbations based on home monitoring data. Clinical application remains challenging in settings with low event incidence and high false alarm rates with high sensitivity.

Abstract Using semen data from 1271 ejaculates (79 different bulls, 11 different breeds) we have investigated the variability of semen quality in cattle living in sub-tropical conditions. Modelling shows definitive evidence of seasonal variation. Semen quality from the same bulls had a 90% “pass rate” for cryopreservation purposes in winter, dropping to less than 50% in summer. Notably, individual bulls could be classified as either “heat-tolerant” (produce good quality spermatozoa all year regardless of temperature) or “heat-sensitive” (only produce good quality sperm in summer). Nominal logistic regression demonstrated when temperatures reach 30.5 °C, 40% of heat-sensitive bulls fail a semen analysis 17 days later. At 34 °C, the proportion of bulls failing reached 63%. Ratifying this, the purposeful heating of bulls to 40 °C for 12 h showed that individual animals had different degrees of heat-sensitivity. Using historical temperature data, we then modelled how many days/decade bulls would be subject to heat-events. Beginning from 1939 to 1949, on average, the area in which bulls were kept recorded 19, 7 and 1 day over 38 °C, 39 °C and 40 °C respectively. This number steadily increases and of last decade (2010–2010), the numbers of days per decade over 38 °C, 39 °C and 40 °C jumped to a staggering 75, 39 and 15 respectively. These data show the urgent need to identify heat-tolerant bulls as future sires. Such variation likely explains why the veterinary bull breeding test often fails to accurately predict bull breeding potential.

The endothelial cells (ECs) make up the inner lining of blood vessels, acting as a barrier separating the blood and the tissues in several organs. ECs maintain endothelium integrity by controlling the constriction and relaxation of the vasculature, blood fluidity, adhesion, and migration. These actions of ECs are efficiently coordinated via an intricate signaling network connecting receptors, and a wide range of cellular macromolecules. ECs are naturally quiescent i.e.; they are not stimulated and do not proliferate. Upon infection or disease, ECs become activated, and this alteration is pivotal in the pathogenesis of a spectrum of human neurological, cardiovascular, diabetic, cancerous, and viral diseases. Considering the central position that ECs play in disease pathogenesis, therapeutic options have been targeted at improving ECs integrity, assembly, functioning, and health. The dietary intake of flavonoids present in citrus fruits has been associated with a reduced risk of endothelium dysfunction. Naringenin (NGN) and Naringin (NAR), major flavonoids in grapefruit, tomatoes, and oranges possess anti-inflammatory, antioxidant properties, and cell survival potentials, which improve the health of the vascular endothelium. In this review, we provide a comprehensive summary and present the advances in understanding of the mechanisms through which NGN and NAR modulate the biomarkers of vascular dysfunction and protect the endothelium against unresolved inflammation, oxidative stress, atherosclerosis, and angiogenesis. We also provide perspectives and suggest further studies that will help assess the efficacy of citrus flavonoids in the therapeutics of human vascular diseases.

Glaucomatous neurodegeneration, a blinding disease affecting millions worldwide, has a need for the exploration of new and effective therapies. Previously, the glucagon-like peptide-1 receptor (GLP-1R) agonist NLY01 was shown to reduce microglia/macrophage activation, rescuing retinal ganglion cells after IOP elevation in an animal model of glaucoma. GLP-1R agonist use is also associated with a reduced risk for glaucoma in patients with diabetes. In this study, we demonstrate that several commercially available GLP-1R agonists, administered either systemically or topically, hold protective potential in a mouse model of hypertensive glaucoma. Further, the resulting neuroprotection likely occurs through the same pathways previously shown for NLY01. This work contributes to a growing body of evidence suggesting that GLP-1R agonists represent a viable therapeutic option for glaucoma.

For solar-type stars, spots and their associated magnetic regions induce radial velocity perturbations through the Doppler rotation signal and the suppression of convective blueshift, collectively known as rotation modulation. We developed the Rotation–Convection (RC) model: a method of detrending and characterizing rotation modulation using only cross–correlation functions or one-dimensional spectra without the need for continuous high-cadence measurements. The RC method uses a simple model for the anomalous radial velocity induced by an active region and has two inputs: stellar flux (or a flux proxy) and the relative radial velocity between strongly and weakly absorbed wavelengths (analogous to the bisector–inverse slope). On NEID solar data (3 month baseline), the RC model lowers the amplitude of rotationally modulated stellar activity to below the meter–per–second level. For the standard star HD 26965, the RC model detrends the activity signal to the meter–per–second level for HARPS, EXPRES, and NEID observations, even though the temporal density and time span of the observations differ by an order of magnitude between the three data sets. In addition to detrending, the RC model also characterizes the rotation–modulation signal. From comparison with the Solar Dynamics Observatory, we confirmed that the model accurately recovers and separates the rotation and convection radial velocity components. We also mapped the amplitude of the rotation and convection perturbations as a function of height within the stellar atmosphere. Probing stellar atmospheres with our revised spot model will fuel future innovations in stellar activity mitigation, enabling robust exoplanet detection.

Gene therapy holds promise as a life-changing option for individuals with genetic variants that give rise to disease. FDA-approved gene therapies for Spinal Muscular Atrophy (SMA), cerebral adrenoleukodystrophy, β-Thalassemia, hemophilia A/B, retinal dystrophy, and Duchenne Muscular Dystrophy have generated buzz around the ability to change the course of genetic syndromes. However, this excitement risks over-expansion into areas of genetic disease that may not fit the current state of gene therapy. While in situ (targeted to an area) and ex vivo (removal of cells, delivery, and administration of cells) approaches show promise, they have a limited target ability. Broader in vivo gene therapy trials have shown various continued challenges, including immune response, use of immune suppressants correlating to secondary infections, unknown outcomes of overexpression, and challenges in driving tissue-specific corrections. Viral delivery systems can be associated with adverse outcomes such as hepatotoxicity and lethality if uncontrolled. In some cases, these risks are far outweighed by the potentially lethal syndromes for which these systems are being developed. Therefore, it is critical to evaluate the field of genetic diseases to perform cost–benefit analyses for gene therapy. In this work, we present the current state while setting forth tools and resources to guide informed directions to avoid foreseeable issues in gene therapy that could prevent the field from continued success.

Abstract Background Despite an established taxonomy of implementation strategies, minimal guidance exists for how to select and tailor strategies to specific practices and contexts. We employed a replicable method to obtain stakeholder perceptions of the most feasible and important implementation strategies to increase mental health providers’ use of measurement-based care (MBC) in schools. MBC is the routine use of patient-reported progress measures throughout treatment to inform patient-centered, data-driven treatment adjustments. Methods A national sample of 52 school mental health providers and researchers completed two rounds of modified Delphi surveys to rate the relevance, importance, and feasibility of 33 implementation strategies identified for school settings. Strategies were reduced and definitions refined using a multimethod approach. Final importance and feasibility ratings were plotted on “go-zone” graphs and compared across providers and researchers to identify top-rated strategies. Results The initial 33 strategies were rated as “relevant” or “relevant with changes” to MBC in schools. Importance and feasibility ratings were high overall for both survey rounds; on a scale of 1 to 5, importance ratings (3.61–4.48) were higher than feasibility ratings (2.55–4.06) on average. Survey 1 responses resulted in a reduced, refined set of 21 strategies, and six were rated most important and feasible on Survey 2: (1) assess for readiness and identify barriers and facilitators; (2) identify and prepare champions; (3) develop a usable implementation plan; (4) offer a provider-informed menu of free, brief measures; (5) develop and provide access to training materials; and (6) make implementation easier by removing burdensome documentation tasks. Provider and researcher ratings were not significantly different, with a few exceptions: providers reported higher feasibility and importance of removing burdensome paperwork than researchers, providers reported higher feasibility of train-the trainer approaches than researchers, and researchers reported higher importance of monitoring fidelity than providers. Conclusions The education sector is the most common setting for child and adolescent mental health service delivery in the USA. Effective MBC implementation in schools has the potential to elevate the quality of care received by many children, adolescents, and their families. This empirically derived, targeted list of six implementation strategies offers potential efficiencies for future testing of MBC implementation in schools.

Background The use of anti-interleukin-5 (IL5) for severe asthma is based on criteria from randomised controlled trials (RCTs), but in real-life patients might not fulfil the eligibility criteria but may benefit from biologics. We aimed to characterise patients starting anti-IL5(R) in Europe and evaluate the discrepancies between initiation of anti-IL5(R) in real life and in RCTs. Materials and methods We performed a cross-sectional analysis with data from the severe asthma patients at the start of anti-IL5(R) in the Severe Heterogeneous Asthma Research collaboration Patient-centred (SHARP Central) registry. We compared the baseline characteristics of the patients starting anti-IL5(R) from 11 European countries within SHARP with the baseline characteristics of the severe asthma patients from 10 RCTs (four for mepolizumab, three for benralizumab and three for reslizumab). Patients were evaluated following eligibility criteria from the RCTs of anti-IL5 therapies. Results Patients starting anti-IL5(R) in Europe (n=1231) differed in terms of smoking history, clinical characteristics and medication use. The characteristics of severe asthma patients in the SHARP registry differed from the characteristics of patients in RCTs. Only 327 (26.56%) patients fulfilled eligibility criteria of all the RCTs; 24 patients were eligible for mepolizumab, 100 for benralizumab and 52 reslizumab. The main characteristics of ineligibility were: ≥10 pack-years, respiratory diseases other than asthma, Asthma Control Questionnaire score ≤1.5 and low-dose inhaled corticosteroids. Conclusion A large proportion of patients in the SHARP registry would not have been eligible for anti-IL5(R) treatment in RCTs, demonstrating the importance of real-life cohorts in describing the efficacy of biologics in a broader population of patients with severe asthma.

Background An objective of the Severe Heterogeneous Asthma Registry, Patient-centered (SHARP) is to produce real-world evidence on a pan-European scale by linking nonstandardised, patient-level registry data. Mepolizumab has shown clinical efficacy in randomised controlled trials and prospective real-world studies and could therefore serve as a proof of principle for this novel approach. The aim of the present study was to harmonise data from 10 national severe asthma registries and characterise patients receiving mepolizumab, assess its effectiveness on annual exacerbations and maintenance oral glucocorticoid (OCS) use, and evaluate treatment patterns. Methods In this observational cohort study, registry data (5871 patients) were extracted for harmonisation. Where harmonisation was possible, patients who initiated mepolizumab between 1 January 2016 and 31 December 2021 were examined. Changes of a 12-month (range 11–18 months) period in frequent (two or more) exacerbations, maintenance OCS use and dose were analysed in a privacy-preserving manner using meta-analysis of generalised estimating equation parameters. Periods before and during the coronavirus disease 2019 pandemic were analysed separately. Results In 912 patients who fulfilled selection criteria, mepolizumab significantly reduced frequent exacerbations (OR 0.18, 95% CI 0.13–0.25), maintenance OCS use (OR 0.75, 95% CI 0.61–0.92) and dose (mean −3.93 mg·day−1, 95% CI −5.24–2.62 mg·day−1) in the pre-pandemic group, with similar trends in the pandemic group. Marked heterogeneity was observed between registries in patient characteristics and mepolizumab treatment patterns. Conclusions By harmonising patient-level registry data and applying federated analysis, SHARP demonstrated the real-world effectiveness of mepolizumab on asthma exacerbations and maintenance OCS use in severe asthma patients across Europe, consistent with previous evidence. This paves the way for future pan-European real-world severe asthma studies using patient-level data in a privacy-proof manner.

Background Benralizumab is highly effective in many, but not all, patients with severe asthma. Baseline characteristics alone are insufficient to predict an individual's probability of long-term benralizumab response. The objectives of the present study were to: 1) study whether parameters at 3 months, in addition to baseline characteristics, contribute to the prediction of benralizumab response at 1 year; and 2) develop an easy-to-use prediction tool to assess an individual's probability of long-term response. Methods We assessed the effect of benralizumab treatment in 192 patients from the Dutch severe asthma registry (RAPSODI). To investigate predictors of long-term benralizumab response (≥50% reduction in maintenance oral corticosteroid (OCS) dose or annual exacerbation frequency) we used logistic regression, including baseline characteristics and 3-month Asthma Control Questionnaire (ACQ-6) score and maintenance OCS dose. Results Benralizumab treatment significantly improved several clinical outcomes, and 144 (75%) patients were classified as long-term responders. Response prediction improved significantly when 3-month outcomes were added to a predictive model with baseline characteristics only (area under the receiver-operating characteristic (AUROC) 0.85 versus 0.72, p=0.001). Based on this model, a prediction tool using sex, prior biologic use, baseline blood eosinophils, forced expiratory volume in 1 s, and at 3 months OCS dose and ACQ-6 was developed which classified patients into three categories with increasing probability of long-term response (95% CI): 25% (3–65%), 67% (57–77%) and 97% (91–99%), respectively. Conclusion In addition to baseline characteristics, treatment outcomes at 3 months contribute to the prediction of benralizumab response at 1 year in patients with severe eosinophilic asthma. Prediction tools as proposed in this study may help physicians optimise the use of costly biologics.

In this paper, the quartz crystal microbalance with dissipation monitoring (QCM-D) was used to investigate hydrophobicity and binding strength (KD) for 10 different drugs interacting with human serum albumin (HSA). Quantitative structure activity relationship (QSAR) analysis was used to determine the relationship between drug hydrophobicity (ClogP) and HSA binding strength log(1/KD). The results are compared to prior knowledge on bovine serum albumin (BSA) binding. We demonstrate a positive correlation between drug hydrophobicity and the strength of ligand-protein binding to HSA and show a statistically significant similarity with the trend reported in BSA. The findings presented in this work provide insight into the role that bound water plays in ligand-protein interactions. Further, the comparison between HSA and BSA provides quantitative justification for the use of these proteins interchangeably in the analysis of drug-based binding kinetics.

Abstract Defective gastrointestinal barrier function and, in turn, microbial translocation have been identified as significant contributors to persistent inflammation in antiretroviral (ARV)-treated people living with HIV. Metabolic supplementation of short-chain fatty acids (SCFAs), generally produced by the commensal microbiome, may improve these outcomes. Butyrate is a SCFA that is essential for the development and maintenance of intestinal immunity and has a known role in supporting epithelial integrity. Herein we assessed whether supplementation with the dietary supplement sodium butyrate would improve immune reconstitution and reduce inflammation in ARV-treated, simian immunodeficiency virus (SIV)-infected rhesus macaques. We demonstrate that butyrate supplementation does not significantly improve immune reconstitution, with no differences observed in systemic CD4+ T-cell frequencies, T-cell functionality or immune activation, microbial translocation, or transcriptional regulation. Our findings demonstrate that oral administration of sodium butyrate is insufficient to reduce persistent inflammation and microbial translocation in ARV-treated, SIV-infected macaques, suggesting that this therapeutic may not reduce co-morbidities and co-mortalities in treated people living with HIV.

Although blood DNA methylation (DNAm) profiles are reported to be associated with breast cancer incidence, they have not been widely used in breast cancer risk assessment. Among a breast cancer case–cohort of 2774 women (1551 cases) in the Sister Study, we used candidate CpGs and DNAm estimators of physiologic characteristics to derive a methylation‐based breast cancer risk score, mBCRS. Overall, 19 CpGs and five DNAm estimators were selected using elastic net regularization to comprise mBCRS. In a test set, higher mBCRS was positively associated with breast cancer incidence, showing similar strength to the polygenic risk score (PRS) based on 313 single nucleotide polymorphisms (313 SNPs). Area under the curve for breast cancer prediction was 0.60 for self‐reported risk factors (RFs), 0.63 for PRS, and 0.63 for mBCRS. Adding mBCRS to PRS and RFs improved breast cancer prediction from 0.66 to 0.71. mBCRS findings were replicated in a nested case–control study within the EPIC‐Italy cohort. These results suggest that mBCRS, a risk score derived using blood DNAm, can be used to enhance breast cancer prediction.