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Abstract Background The UK Soft Drinks Industry Levy (SDIL) was announced in March 2016, became law in April 2017, and was implemented in April 2018. Empirical analyses of commercial responses have not been undertaken to establish the scale, direction or nuance of industry media messaging around fiscal policies. We aimed to develop a detailed understanding of industry reactions to the SDIL in publicly available media, including whether and how these changed from announcement to implementation. Methods We searched Factiva to identify articles related to sugar, soft-drinks, and the SDIL, between 16th March 2016–5th April 2018. Articles included were UK publications written in English and reporting a quotation from an industry actor in response to the SDIL. We used a longitudinal thematic analysis of public statements by the soft-drinks industry that covered their reactions in relation to key policy milestones. Results Two hundred and ninety-eight articles were included. After the announcement in March 2016, there was strong opposition to the SDIL. After the public consultation, evolving opposition narratives were seen. After the SDIL became law, reactions reflected a shift to adapting to the SDIL. Following the publication of the final regulations, statements sought to emphasise industry opportunities and ensure the perceived profitability of the soft drinks sector. The most significant change in message (from opposition to adapting to the SDIL) occurred when the SDIL was implemented (6th April 2018). Conclusion Reactions to the SDIL changed over time. Industry modified its media responses from a position of strong opposition to one that appeared to focus on adaptation and maximising perceived profitability after the SDIL became law. This shift suggests that the forces that shape industry media responses to fiscal policies do not remain constant but evolve in response to policy characteristics and the stage of the policy process to maximise beneficial framing.

Background: Anxiety and depression can affect adolescents’ health and current literature lacks studies of youths living in non-urban settings. Methods: We used chi-square and t-tests on data collected from self-administered online surveys, completed by 9th-grade students (n=222) attending a large, semi-rural public high school in the state of Georgia, to assess the prevalence of symptoms of anxiety and depression and associated factors. Results: Almost half of the students self-reported anxiety (43%) or depression (55%) and students who self-reported either condition were more likely to report poorer sleep hygiene, sleepiness, race-related mistreatment, and higher stress. Conclusions: Our findings suggest that symptoms of anxiety and depression are prevalent among youths in semi-rural settings and further research is needed to understand the role of modifiable risk factors and identify effective interventions. Keywords: adolescent mental health; adolescent sleep; anxiety; depression; semi-rural

The domain wall-magnetic tunnel junction (DW-MTJ) is a versatile device that can simultaneously store data and perform computations. These three-terminal devices are promising for digital logic due to their nonvolatility, low-energy operation, and radiation hardness. Here, we augment the DW-MTJ logic gate with voltage-controlled magnetic anisotropy (VCMA) to improve the reliability of logical concatenation in the presence of realistic process variations. VCMA creates potential wells that allow for reliable and repeatable localization of domain walls (DWs). The DW-MTJ logic gate supports different fanouts, allowing for multiple inputs and outputs for a single device without affecting the area. We simulate a systolic array of DW-MTJ multiply-accumulate (MAC) units with 4-bit and 8-bit precision, which uses the nonvolatility of DW-MTJ logic gates to enable fine-grained pipelining and high parallelism. The DW-MTJ systolic array provides comparable throughput and efficiency to state-of-the-art CMOS systolic arrays while being radiation-hard. These results improve the feasibility of using DW-based processors, especially for extreme-environment applications such as space.

Here, we report the ability of spiropyrans to initiate two-photon polymerization (TPP) for the first time in the literature. The comparison and synergies between the spiropyran photochromic molecule of interest, namely 6-nitro-BIPS, and well-known photoinitiators of radical photopolymerization have been studied. The spiropyran (SPy) molecule can initiate TPP in the presence of trifunctional acrylic monomers and create true 3D structures. The comparison with Irgacure 819, a well-known Type-I photoinitiator, shows that SPy has a comparable capability for TPP. In addition, the combination of SPy with methyl diethanolamine increased the reactivity of both one- and two-photon polymerizations. In the last section, we discuss which SPy isomer is the active photochromic species capable of generating radicals for initiating two-photon polymerization.

Abstract Background Quantitative and qualitative procedures are necessary components of instrument development and assessment. However, validation studies conventionally emphasise quantitative assessments while neglecting qualitative procedures. Applying both methods in a mixed methods design provides additional insights into instrument quality and more rigorous validity evidence. Drawing from an extensive review of the methodological and applied validation literature on mixed methods, we showcase our use of mixed methods for validation which applied the quality criteria of congruence, convergence, and credibility on data collected with an instrument measuring interprofessional collaboration in the context of Swiss healthcare, named the Swiss Instrument for Evaluating Interprofessional Collaboration. Methods We employ a convergent parallel mixed methods design to analyse quantitative and qualitative questionnaire data. Data were collected from staff, supervisors, and patients of a university hospital and regional hospitals in the German and Italian speaking regions of Switzerland. We compare quantitative ratings and qualitative comments to evaluate the quality criteria of congruence, convergence, and credibility, which together form part of an instrument’s construct validity evidence. Results Questionnaires from 435 staff, 133 supervisors, and 189 patients were collected. Analysis of congruence potentially provides explanations why respondents’ comments are off topic. Convergence between quantitative ratings and qualitative comments can be interpreted as an indication of convergent validity. Credibility provides a summary evaluation of instrument quality. These quality criteria provide evidence that questions were understood as intended, provide construct validity, and also point to potential item quality issues. Conclusions Mixed methods provide alternative means of collecting construct validity evidence. Our suggested procedures can be easily applied on empirical data and allow the congruence, convergence, and credibility of questionnaire items to be evaluated. The described procedures provide an efficient means of enhancing the rigor of an instrument and can be used alone or in conjunction with traditional quantitative psychometric approaches.

Abstract Many studies have described the diversity of Austronesian-speaking Taiwanese people to shed more light on their origin and their connection with the “Out of Taiwan” migrations. However, the genetic relationship between the non-Austronesian-speaking groups of Taiwan and the populations of continental Asia is still unclear. Here, we studied the diversity of mtDNA in 767 non-Austronesian speakers from 16 locations in Taiwan using partial sequencing obtained from the hypervariable segment I (HVS-I) and coding regions 8,001-9,000 and 9.801–10,900 and 85 complete mtDNA genome sequences. Bayesian analysis of population structure was used to examine their relationship with over 3662 individuals representing indigenous groups of Taiwan, continental East Asia, Japan, and Island Southeast Asia. The whole analysis identified 278 haplotypes. Complete genomes revealed 62 novel subhaplogroups, of which 31 were exclusive to Taiwan. Estimates of coalescence times of all subhaplogroups showed peaks of diversification greater than 5.0 kya, likely characterizing gene flow from continental East Asian groups but not excluding in situ Taiwanese ancestry. Furthermore, a significant number of clades exclusive to non-Austronesian speakers of Taiwan (NAN_Tw) showed coalescence peaks between 1.0 and 2.6 kya, suggesting possible late Neolithic to early metal age settlements of NAN_Tw and local expansion in Taiwan.

The specific properties and availability of banana pseudo-trunk fibers make them a promising alternative for the development of green composites. However, the wide dispersion of their properties can hinder their use. In this study, the influence of the sampling area of the banana pseudo-trunk on the physical and mechanical properties of the fibers was evaluated. Prior to retting, the trunk was sampled longitudinally (bottom, middle and top) and transversely (periphery, intermediate and heart). Gravimetric tests were carried out and revealed variations in water absorption (347.1–517.4%), density (0.92–1.45 g.cm−3) and linear mass (25 -34tex). Tensile tests were also performed and showed a significant effect of fiber location on Young’s modulus (6.60–34.6GPa), tensile strength (91-350MPa) and elongation at the break (0.9–2.6%). Due to diameter scatter, variations of 42% were found for fibers in the same area. In a region, the physical properties increase from the periphery to the core, and the mechanical properties decrease in the same direction, except for elongation. The results of this study showed good agreement with those of other natural fiber types. However, we recommend the peripheral areas of the pseudo-trunk to extract reinforcing fibers from composites because of their low density (0.9 g.cm−3) and their high stiffness (34GPa).

This study aims at identifying molecular biomarkers differentiating responders and non-responders to treatment with Tumor Necrosis Factor inhibitors (TNFi) among patients with axial spondyloarthritis (axSpA). Whole blood mRNA and plasma proteins were measured in a cohort of biologic-naïve axSpA patients (n = 35), pre and post (14 weeks) TNFi treatment with adalimumab. Differential expression analysis was used to identify the most enriched pathways and in predictive models to distinguish responses to TNFi. A treatment-associated signature suggests a reduction in inflammatory activity. We found transcripts and proteins robustly differentially expressed between baseline and week 14 in responders. C-reactive protein (CRP) and Haptoglobin (HP) proteins showed strong and early decrease in the plasma of axSpA patients, while a cluster of apolipoproteins (APOD, APOA2, APOA1) showed increased expression at week 14. Responders to TNFi treatment present higher levels of markers of innate immunity at baseline, and lower levels of adaptive immunity markers, particularly B-cells. A logistic regression model incorporating ASDAS-CRP, gender, and AFF3, the top differentially expressed gene at baseline, enabled an accurate prediction of response to adalimumab in our cohort (AUC = 0.97). In conclusion, innate and adaptive immune cell type composition at baseline may be a major contributor to response to adalimumab in axSpA patients. A model including clinical and gene expression variables should also be considered.

Overexpression of isoform δ of phosphoinositide 3-kinase (PI3Kδ) promotes stemness in hepatocellular carcinoma cell lines and mouse liver, whereas its inhibition promotes EMT, suggesting a key role for PI3Kδ in epithelial plasticity.

Islet transplantation for type 1 diabetes management is hindered by the life-long need for immunosuppressive medications. Here, the authors report an islet encapsulation device with local anti-rejection drug release that achieves long-term diabetes reversal in male rats and reduces drug-related toxicity.

Abstract Background Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability in males and the most common single gene cause of autism. This X-linked disorder is caused by an expansion of a trinucleotide CGG repeat (> 200 base pairs) on the promotor region of the fragile X messenger ribonucleoprotein 1 gene (FMR1). This leads to the deficiency or absence of the encoded protein, fragile X messenger ribonucleoprotein 1 (FMRP). FMRP has a central role in the translation of mRNAs involved in synaptic connections and plasticity. Recent studies have demonstrated the benefit of therapeutics focused on reactivation of the FMR1 locus towards improving key clinical phenotypes via restoration of FMRP and ultimately disease modification. A key step in future studies directed towards this effort is the establishment of proof of concept (POC) for FMRP reactivation in individuals with FXS. For this, it is key to determine the feasibility of repeated collection of tissues or fluids to measure FMR1 mRNA and FMRP. Methods Individuals, ages 3 to 22 years of age, with FXS and those who were typically developing participated in this single-site pilot clinical biomarker study. The repeated collection of hair follicles was compared with the collection of blood and buccal swabs for detection of FMR1 mRNA and FMRP and related molecules. Results There were n = 15 participants, of whom 10 had a diagnosis of FXS (7.0 ± 3.56 years) and 5 were typically developing (8.2 ± 2.77 years). Absolute levels of FMRP and FMR1 mRNA were substantially higher in healthy participants compared to full mutation and mosaic FXS participants and lowest in the FXS boys. Measurement of FMR1 mRNA and FMRP levels by any method did not show any notable variation by collection location at home versus office across the various sample collection methodologies of hair follicle, blood sample, and buccal swab. Conclusion Findings demonstrated that repeated sampling of hair follicles in individuals with FXS, in both, home, and office settings, is feasible, repeatable, and can be used for measurement of FMR1 mRNA and FMRP in longitudinal studies.

Le mouvement de décolonisation au sein des institutions universitaires du continent africain s’est traduit au Sénégal par le recrutement d’un personnel africain et par un effort constant dans la confection des curricula. Qu’en est-il ailleurs, au sein d’institutions qui sont ancrées dans le passé colonial des États qui les abritent ? Le cas canadien, du fait de son histoire avec les peuples autochtones, permet aussi de mettre en perspective les dimensions oppressives du point de vue épistémologique et hiérarchique au sein des univers académiques. Cette contribution propose une réflexion sur ces enjeux à partir d’une collaboration pédagogique entre deux collègues appartenant respectivement à une institution sénégalaise et canadienne. Nous arguons que les rapports de pouvoir ancrés dans l’histoire coloniale au sein de l’université peuvent être renégociés grâce à l’ouverture d’espaces d’enseignement alternatifs. Ces derniers, en initiant des programmes et cours innovants reposant sur une collaboration décomplexée et mobilisant une pédagogie sensible peuvent permettre une réelle décolonisation pédagogique et des méthodologies de recherche.

Background The World Health Organization (WHO) recommends that countries implement fiscal policies to reduce the health impacts of sugary drinks. Few studies have fully examined the responses of industry to these policies, and whether they support or undermine health benefits of sugary drinks taxes. We aimed to explore the changes that sugary drinks companies may make to their marketing, and underlying decision-making processes, in response to such a tax.Methods Following introduction of the UK Soft Drinks Industry Levy (SDIL) in 2018, we undertook one-to-one semi-structured interviews with UK stakeholders with experience of the strategic decision-making or marketing of soft drinks companies. We purposively recruited interviewees using seed and snowball sampling. We conducted telephone interviews with 6 representatives from each of industry, academia and civil society (total n=18), which were transcribed verbatim and thematically analysed. Four transcripts were double-coded, three were excluded from initial coding to allow comparison; and findings were checked by interviewees.Results Themes were organised into a theoretical framework that reveals a cyclical, iterative and ongoing process of soft drinks company marketing decision-making, which was accelerated by the SDIL. Decisions about marketing affect a product’s position, or niche, in the market and were primarily intended to maintain profits. A product’s position is enacted through various marketing activities including reformulation and price variation, and non-marketing activities like lobbying. A soft drinks company’s selection of marketing activities appeared to be influenced by their internal context, such as brand strength, and external context, such as consumer trends and policy. For example, a company with low brand strength and an awareness of trends for reducing sugar consumption may be more likely to reformulate to lower-sugar alternatives.Conclusion The theoretical framework suggests that marketing responses following the SDIL were coordinated and context-dependent, potentially explaining observed heterogeneity in responses across the industry.

Abstract CXCL8 is an inflammatory chemokine elevated in the colorectal cancer (CRC) tumour microenvironment. CXCR2, the major receptor for CXCL8, is predominantly expressed by neutrophils. In the cancer setting, CXCL8 plays important roles in neutrophil chemotaxis, facilitating angiogenesis, invasion, and metastasis. This study aimed to assess the spatial distribution of CXCL8 mRNA expression in CRC specimens, explore associations with clinical characteristics, and investigate the underlying biology of aberrant CXCL8 levels. CXCR2 expression was also assessed in a second cohort of unique CRC primary tumours and synchronously resected matched liver metastases. A previously constructed tissue microarray consisting of a cohort of stage I–IV CRC patients undergoing surgical resection with curative intent (n = 438) was probed for CXCL8 via RNAscope®. Analysis was performed using HALO® digital pathology software to quantify expression in the tumour and stromal compartments. Scores were assessed for association with clinical characteristics. Mutational analyses were performed on a subset of these patients to determine genomic differences in patients with high CXCL8 expression. A second cohort of stage IV CRC patients with primary and matched metastatic liver tumours was stained via immunohistochemistry for CXCR2, and scores were assessed for clinical significance. CXCL8 expression within the stromal compartment was associated with reduced cancer‐specific survival in the first cohort (p = 0.035), and this relationship was potentiated in right‐sided colon cancer cases (p = 0.009). High CXCL8 within the stroma was associated with driving a more stromal‐rich phenotype and the presence of metastases. When stromal CXCL8 scores were combined with tumour‐infiltrating macrophage counts or systemic neutrophil counts, patients classified as high for both markers had significantly poorer prognosis. CXCR2+ immune cell infiltration was associated with increased stromal invasion in liver metastases (p = 0.037). These data indicate a role for CXCL8 in driving unfavourable tumour histological features and promoting metastases. This study suggests that inhibiting CXCL8/CXCR2 should be investigated in patients with right‐sided colonic disease and stroma‐rich tumours.

Patricia Grace est une auteure māori de renom. Son deuxième roman Pōtiki est paru en anglais en 1986, puis en français en 1993. Récemment, la maison d’édition tahitienne Au vent des îles, qui a publié les autres romans de Grace, nous a demandé de retraduire cette œuvre. Nous expliquerons ici notre démarche, qui suit une approche post-coloniale, tenant compte de l’enracinement historique et social de l’œuvre

Longtemps ignorée par les chercheurs en sciences sociales, l’abstention électorale devient une des problématiques majeures de la démocratie représentative en ce moment. Tel est également le cas pour Madagascar. Ce phénomène d’abstention trouve ses sources dans plusieurs facteurs. En outre, cette situation n’est pas sans conséquence pour le fonctionnement normal des institutions. En effet, elle entraîne la remise en cause de la crédibilité des dirigeants issus de l’élection. Mais, l’intérêt de l’étude approfondie de la dynamique de l’abstention permet de faire ressortir le profil des abstentionnistes ainsi que les raisons de leur choix afin de proposer des solutions pour y remédier.

Madagascar est le seul pays dans le monde où le PIB par tête n’a cessé de régresser depuis l’indépendance. Une situation qui est à la fois préoccupante et étonnante pour les chercheurs, observateurs et experts de différentes disciplines. Plusieurs variables ont été avancées pour expliquer cette situation. Les élites malgaches sont à l’origine de la situation dans laquelle le pays se trouve du fait de leurs échecs dans plusieurs domaines : l’échec dans la conduite des affaires publiques (régression économique, incohérence des actions publiques, dépendance vis-à-vis de l’aide au développement), l’échec dans la conduite des affaires privées (incapacité à développer une culture entrepreneuriale, incapacité à créer des confiances devant les bailleurs, difficile intégration dans le jeu concurrentiel mondial) et échec dans la construction d’un Etat au sens moderne ( échec dans l’édification d’un contrat social fort, échec dans la mise en œuvre d’un système démocratique, échec dans la consolidation d’une nation malgache).

The challenges faced by caregivers, encompassing mental, emotional, physical, social, and spiritual dimensions, represent a critical area of study for healthcare professionals aiming to offer comprehensive support. This study, conducted at a Manila tertiary hospital over two weeks in April 2023, utilized an in-depth interview guide to explore the experiences of four diverse caregivers tending to individuals in a vegetative state. Findings revealed four prominent themes: the willingness to assume the caregiver role, lifestyle and social alterations, fear of the unknown, and personal struggles along with coping mechanisms and support systems. The intimate, personal interviews provided a deep understanding of the caregivers' multifaceted challenges. Caring for a loved one in a vegetative state demands substantial emotional and physical tolls, leading to daily anxiety and concern. Recognizing the complexities of their situation and providing the necessary support can significantly alleviate the burdens they face. Moreover, for these caregivers, it becomes a way to reciprocate the love and care previously bestowed upon their loved ones enduring such a condition. This exploration underscores the demanding nature of caring for those in a vegetative state within a familial setting, highlighting the imperative need for holistic support systems and interventions. Understanding the intricacies of caregivers' experiences is pivotal in designing effective strategies to mitigate their challenges and offer the necessary assistance and care.

Dysfunction of visceral smooth muscle (“visceral myopathy”) impairs bowel, bladder, and uterine function. Symptoms of this life-threatening condition include massive intestinal distension with slow transit, vomiting, feeding intolerance, growth failure, poor bladder emptying, and difficult vaginal delivery. The most common genetic cause of visceral myopathy is a heterozygous point mutation (R257C) in gamma smooth muscle actin (ACTG2). We genetically modified the WAe0009-A human embryonic stem cell line to carry the c.769C>T p.R257C/+ mutation. This cell line will facilitate studies of how the ACTG2 R257C heterozygous variant affects smooth muscle development and function.

Visceral myopathies are debilitating conditions characterized by dysfunction of smooth muscle in visceral organs (bowel, bladder, and uterus). Individuals affected by visceral myopathy experience feeding difficulties, growth failure, life-threatening abdominal distension, and may depend on intravenous nutrition for survival. Unfortunately, our limited understanding of the pathophysiology of visceral myopathies means that current therapies remain supportive, with no mechanism-based treatments. We developed a patient-derived iPSC line with a c.769C > T p.R257C/+ mutation, the most common genetic cause of visceral myopathy. This cell line will facilitate studies of how the ACTG2 R257C heterozygous variant affects smooth muscle development and function.

The CHOPWT17_TPM1KOc28 iPSC line was generated to interrogate the functions of Tropomyosin 1 (TPM1) in primary human cell development. This line was reprogrammed from a previously published wild type control iPSC line.

Post-transplant lymphoproliferative disorder (PTLD) is a potentially fatal complication following kidney transplantation, and there is a critical and unmet need for PTLD treatments associated with more pronounced and durable responses. To date, reports on the use of CD19-targeted chimeric antigen receptor (CAR) T (CAR-T) cells in patients after solid organ transplant (SOT) have been anecdotal, clinical presentations and outcomes have been heterogenous, and a longitudinal analysis of CAR-T cell expansion and persistence in PTLD patients has not been reported. Our report describes a patient with a history of renal transplant who received CD19-directed CAR-T cell therapy for the treatment of refractory PTLD, diffuse large B cell lymphoma (DLBCL)-type. We show that even with the background of prolonged immunosuppression for SOT, it is possible to generate autologous CAR-T products capable of expansion and persistence in vivo, without evidence of excess T-cell exhaustion. Our data indicate that CAR-T cells generated from a SOT recipient with PTLD can yield deep remissions without increased toxicity or renal allograft dysfunction. Future clinical studies should build on these findings to investigate CAR-T therapy, including longitudinal monitoring of CAR-T phenotype and function, for PTLD in SOT recipients.

ABSTRACT The xanthine oxidoreductase (XOR) family are metal-containing enzymes that use the molybdenum cofactor (Moco), 2Fe-2S clusters, and flavin adenine dinucleotide (FAD) for their catalytic activity. This large molybdoenzyme family includes xanthine, aldehyde, and CO dehydrogenases. XORs are widely distributed from bacteria to humans due to their key roles in the catabolism of purines, aldehydes, drugs, and xenobiotics, as well as interconversions between CO and CO2. Assessing the effect of excess metals on the Rubrivivax gelatinosus bacterium, we found that exposure to copper (Cu) or cadmium (Cd) caused a dramatic decrease in the activity of a high-molecular-weight soluble complex exhibiting nitroblue tetrazolium reductase activity. Mass spectrometry and genetic analyses showed that the complex corresponds to a putative CO dehydrogenase (pCOD). Using mutants that accumulate either Cu+ or Cd2+ in the cytoplasm, we show that Cu+ or Cd2+ is a potent inhibitor of XORs (pCOD and the xanthine dehydrogenase [XDH]) in vivo. This is the first in vivo demonstration that Cu+ affects Moco-containing enzymes. The specific inhibitory effect of these compounds on the XOR activity is further supported in vitro by direct addition of competing metals to protein extracts. Moreover, emphasis is given on the inhibitory effect of Cu on bovine XOR, showing that the XOR family could be a common target of Cu. Given the conservation of XOR structure and function across the tree of life, we anticipate that our findings could be transferable to other XORs and organisms. IMPORTANCE The high toxicity of Cu, Cd, Pb, As, and other metals arises from their ability to cross membranes and target metalloenzymes in the cytoplasm. Identifying these targets provides insights into the toxicity mechanisms. The vulnerability of metalloenzymes arises from the accessibility of their cofactors to ions. Accordingly, many enzymes whose cofactors are solvent exposed are likely to be targets of competing metals. Here, we describe for the first time, with in vivo and in vitro experiments, a direct effect of excess Cu on the xanthine oxidoreductase family (XOR/XDH/pCOD). We show that toxic metal affects these Moco enzymes, and we suggest that access to the Moco center by Cu ions could explain the Cu inhibition of XORs in living organisms. Human XOR activity is associated with hyperuricemia, xanthinuria, gout arthritis, and other diseases. Our findings in vivo highlight XOR as a Cu target and thus support the potential use of Cu in metal-based therapeutics against these diseases.

Objectives The UK Soft Drinks Industry Levy (SDIL), implemented in 2018, has been successful in reducing the sugar content and purchasing of soft drinks, with limited financial impact on industry. Understanding the views of food and drink industry professionals involved in reacting to the SDIL is important for policymaking. However, their perceptions of the challenges of implementation and strategic responses are unknown. The aim of this study, therefore, was to explore how senior food and drink industry professionals viewed the SDIL.Design We undertook a qualitative descriptive study using elite interviews. Data were analysed using Braun and Clarke’s thematic analysis, taking an inductive exploratory and descriptive approach not informed by prior theory or frameworks.Setting and participants Interviews were conducted via telephone with 14 senior professionals working in the food and drink industry.Results Five main themes were identified: (1) a level playing field…for some; industry accepted the SDIL as an attempt to create a level playing field but due to the exclusion of milk-based drinks, this was viewed as inadequate, (2) complex to implement, but no lasting negative effects; the SDIL was complex, expensive and time consuming to implement, with industry responses dependent on leadership buy-in, (3) why us?—the SDIL unfairly targets the drinks industry; soft drinks are an unfair target when other categories also contain high sugar, (4) the consumer is king; consumers were a key focus of the industry response to this policy and (5) the future of the SDIL; there appeared to be a wider ripple effect, which primed industry to prepare for future regulation in support of health and environmental sustainability.Conclusions Insights from senior food and drink industry professionals illustrate how sugar-sweetened beverage taxes might be successfully implemented and improve understanding of industry responses to taxes and other food and drink policies.Trial registration number ISRCTN18042742.

Introduction. In this study, we aimed to determine the factors associated with hypertension, known poorly controlled hypertension, and newly diagnosed hypertension in 2015 to improve the prevention of this pathology in our country. Methods. This was a secondary analysis of the national WHO STEPwise survey database. It had a quantitative, descriptive, and analytical aim. The sampling was done in stratification in three stages of sampling. Statistical analysis was performed using Rstudio 4.0.2 software. It was a descriptive, bivariate, and multivariate analysis using binomial logistic regression for explanatory purposes. Results. The risk factors for being hypertensive among 18-70- year-olds in Senegal in 2015 were: having taken their blood pressure at least once in their life; having taken their cholesterol levels at least once in their life; having received advice to reduce salt consumption; having received advice on how to reduce the amount of sugar; having a lean body mass index; being overweight; being obese III; and being between 35-39 and 65-70 years old. The protective factors are: checking the salt content indicated on the labels; and consuming salt-rich dishes “often” compared to “never”. The risk factors for being newly diagnosed with hypertension among 18-70-year-olds in Senegal in 2015 were: having a history of stroke; having a resting heart rate greater than 80 beats per minute; consuming palm oil; and having high fasting blood sugar. The protective factors are: having a high average number of meals eaten per week not prepared at home; checking the salt content indicated on the label; and being of female sex. The risk factors for being known to have poorly controlled hypertension among 18-70- year-olds in Senegal in 2015 were: judging their reduction in salt consumption as “very important”; and having received advice to reduce their salt consumption. The protective factors are: performing physical activity only when traveling; and limiting the consumption of salty meals. Conclusion. Senegalese family cooking exposes to hypertension, small actions limiting salt consumption strongly protect against hypertension, and simple physical activity during travel strongly protects against hypertension, but the health system is very little proactive in the primordial and primary prevention of hypertension.

Little is known about lipid changes that occur in the setting of metabolic-dysfunction-associated steatotic liver disease (MASLD) regression. We previously reported improvements in hepatic steatosis, de novo lipogenesis (DNL), and metabolomic profiles associated with oxidative stress, inflammation, and selected lipid metabolism in 40 adolescent boys (11–16 y) with hepatic steatosis ≥5% (98% meeting the definition of MASLD). Participants were randomized to a low-free-sugar diet (LFSD) (n = 20) or usual diet (n = 20) for 8 weeks. Here, we employed untargeted/targeted lipidomics to examine lipid adaptations associated with the LFSD and improvement of hepatic steatosis. Our LC-MS/MS analysis revealed decreased triglycerides (TGs), diacylglycerols (DGs), cholesteryl esters (ChE), lysophosphatidylcholine (LPC), and phosphatidylcholine (PC) species with the diet intervention (p < 0.05). Network analysis demonstrated significantly lower levels of palmitate-enriched TG species post-intervention, mirroring the previously shown reduction in DNL in response to the LFSD. Targeted oxylipins analysis revealed a decrease in the abundance of 8-isoprostane and 14,15-DiHET and an increase in 8,9-DiHET (p < 0.05). Overall, we observed reductions in TGs, DGs, ChE, PC, and LPC species among participants in the LFSD group. These same lipids have been associated with MASLD progression; therefore, our findings may indicate normalization of key biological processes, including lipid metabolism, insulin resistance, and lipotoxicity. Additionally, our targeted oxylipins assay revealed novel changes in eicosanoids, suggesting improvements in oxidative stress. Future studies are needed to elucidate the mechanisms of these findings and prospects of these lipids as biomarkers of MASLD regression.

The dessert banana is a popular fruit worldwide, but its ripening process is greatly accelerated by high temperatures, which eventually leads to an unpleasant taste and the appearance of spots on the skin of the fruits. To slow down the ripening of bananas, expensive strategies are used, which are usually not practical for conventional farmers in less developed countries. In this study, we try to find a less costly alternative. Therefore, the effects of coatings of lemon peel extract (2.5%, 5%, and 10%), calcium chloride (4%), and glycerol (2%) on the shelf life and postharvest quality of the banana fruit (Cavendish) stored at 19–22 °C and 40–60% relative humidity were investigated. Treatment with a mixture of 2.5% lemon peel extract and 2% glycerol resulted in an extension of the shelf life of the dessert banana by up to 6 days and no detectable fungal infestation. The coating solution is an effective alternative to extend the shelf life and reduce quality losses in bananas.

Background: Measurement of salivary caffeine (1,3,7-trimethylpurine-2,6-dione or 1,3,7-trimethylxanthine) clearance can, in principle, be used to assess hepatic function, diagnose chronic hepatic disease and conduct investigations of substrates of hepatic cytochrome P450 (CYP) isozymes in children, without recourse to venepuncture. However, little is known about childhood sexual dimorphism of hepatic CYP isoforms. Furthermore, the association, if any, between salivary caffeine clearance and age in children has not hitherto been established. The aims of this study were to assess whether salivary caffeine clearance differs between boys and girls and whether it varies with age during childhood. Methods: Following at least 24 h’ abstinence from dietary caffeine, nine boys (mean (standard error) age 9.6 (1.1) y) and eight girls (mean age 11.0 (1.2) y), none of whom was a smoker or suffered from chronic hepatic disease, ingested an oral caffeine dose titrated by body mass, namely 3 mg kg−1. Salivary samples collected two and 14 h later underwent spectrophotometric caffeine analysis. Results: The boys and the girls were age matched. The mean caffeine clearance in the boys was 2.47 (0.33) mL min−1 kg−1, while that in the girls was 2.20 (0.31) mL min−1 kg−1 (p = 0.56). The salivary caffeine clearance was negatively correlated with age (r = −0.59, p = 0.01). Conclusion: Stratification by sex appears to be unnecessary when considering childhood salivary caffeine clearance or when conducting investigations in children of CYP1A2 and xanthine oxidase substrates. Furthermore, childhood salivary caffeine clearance is negatively correlated with age.

Anthropological and linguistic studies place the first settlement of Austronesian speaking Taiwanese (AN_Tw) in the mid-Holocene era. However, geneticists have revealed exclusive diversity among the Bunun indigenous people, implying that their ancestral origin needs further study. The mitochondrial DNA (mtDNA) polymorphism of the Bunun shows a homogeneous relationship with other AN_Tw. However, the Y-chromosome polymorphism shows two major haplogroups, O1a2-M50 (60.7%), also seen to a lesser extent among the Northern AN_Tw, and O1b1a1a1a1a1-M88 (37.5%), scarce among all other AN and non-AN groups in Taiwan, but prevailing in Southeast Asia (SEA) and Mainland Southeast Asia (MSEA). While the present-day mtDNA profile of the Bunun typifies the long-term demographic standard for all AN_Tw since the Neolithic era, their Y-chromosome profile suggests an arrival of male settlers in the last two to three millennia from SEA or MSEA, who mixed exclusively with the Bunun indigenous people.

Abstract Background Identifying early biomarkers of serious mental illness (SMI)—such as changes in brain structure and function—can aid in early diagnosis and treatment. Whole brain structural and functional connectomes were investigated in youth at risk for SMI. Methods Participants were classified as healthy controls (HC; n = 33), familial risk for serious mental illness (stage 0; n = 31), mild symptoms (stage 1a; n = 37), attenuated syndromes (stage 1b; n = 61), or discrete disorder (transition; n = 9) based on clinical assessments. Imaging data was collected from two sites. Graph-theory based analysis was performed on the connectivity matrix constructed from whole-brain white matter fibers derived from constrained spherical deconvolution of the diffusion tensor imaging (DTI) scans, and from the correlations between brain regions measured with resting state functional magnetic resonance imaging (fMRI) data. Results Linear mixed effects analysis and analysis of covariance revealed no significant differences between groups in global or nodal metrics after correction for multiple comparisons. A follow up machine learning analysis broadly supported the findings. Several non-overlapping frontal and temporal network differences were identified in the structural and functional connectomes before corrections. Conclusions Results suggest significant brain connectome changes in youth at transdiagnostic risk may not be evident before illness onset.

Abstract Anthropogenic activities contribute to changes in the range and distribution of species. Globalization is resulting in human‐mediated dispersal that is causing a breakdown in normal biogeographic barriers. But the impact of anthropogenic activities on plant pathogen communities is still poorly understood. We conducted an eDNA metabarcoding study to compare communities of oomycetes, a group of eukaryotic microorganisms that comprises important crop and tree pathogens, in urban, natural, and interface environments. Oomycete diversity and abundance were highest in human impacted urban environments and lowest in natural environments, while the interface environments were intermediate. Urban environments had the highest proportion of sites where species of the plant pathogenic genus Phytophthora were found, as well as the largest number of unknown or undescribed Phytophthora species. The taxa overlap between urban and interface environments was one order of magnitude larger than the overlap between urban and natural environments. Our analyses show that urban/natural interface areas likely act as a bridge for invasion into natural environments. This could impact both the natural biota and natural ecosystem processes. Our study serves as a warning that some Phytophthora species introduced from nurseries or spread by human movement could pose a threat to natural ecosystems. Shifting patterns in oomycete communities could interfere with natural ecosystem processes and result in increases in disease and ecosystem declines.

Abstract Background Food literacy is theorised to improve diet quality, nutrition behaviours, social connectedness and food security. The definition and conceptualisation by Vidgen & Gallegos, consisting of 11 theoretical components within the four domains of planning and managing, selecting, preparing and eating, is currently the most highly cited framework. However, a valid and reliable questionnaire is needed to comprehensively measure this conceptualisation. Therefore, this study draws on existing item pools to develop a comprehensive food literacy questionnaire using item response theory. Methods Five hundred Australian adults were recruited in Study 1 to refine a food literacy item pool using principal component analysis (PCA) and item response theory (IRT) which involved detailed item analysis on targeting, responsiveness, validity and reliability. Another 500 participants were recruited in Study 2 to replicate item analysis on validity and reliability on the refined item pool, and 250 of these participants re-completed the food literacy questionnaire to determine its test–retest reliability. Results The PCA saw the 171-item pool reduced to 100-items across 19 statistical components of food literacy. After the thresholds of 26 items were combined, responses to the food literacy questionnaire had ordered thresholds (targeting), acceptable item locations ( 0.99) and test–retest (ICC 2,1 0.55–0.88) scores (reliability). Conclusions We developed a 100-item food literacy questionnaire, the IFLQ-19 to comprehensively address the Vidgen & Gallegos theoretical domains and components with good targeting, responsiveness, reliability and validity in a diverse sample of Australian adults.

Abstract Background Pediatric primary healthcare providers are well‐positioned to provide healthy lifestyle and weight management related counseling but many lack training in evidence‐based messages and methods. Objectives We assessed the impact of a brief, easy‐to‐access training for pediatric healthcare providers, (the Strong4Life Provider Training), designed to introduce/review current evidence‐based messages and methods and improve healthy weight‐related assessment and counseling practices. Methods Following their well‐child visit, a convenience sample of children 12–17 years and parents of children 6–11 years (N = 121) of randomly selected Strong4Life trained (N = 15) and untrained (N = 15) pediatricians were administered a survey designed to assess the frequency, content, and patient satisfaction with weight management‐related counseling provided. Results from parents and patients of trained pediatricians (N = 62) compared to those from parents and patients of untrained pediatricians (n = 59) were compared using chi‐square tests. Generalized estimating equations were used to account for lack of independence among respondents from the same practice. P‐values less than 0.05 were considered to be statistically significant. Results Parents/patients of trained pediatricians were more likely than those of an untrained pediatrician to report having been asked about child's consumption of fruit/vegetables, 57 (92%) versus 44 (75%), p = 0.04 and sugary drinks, 50 (81%) versus 29 (49%), p = 0.005, and their readiness for behavior change, 47 (76%) versus 29 (49%), p = 0.005, and to set a behavior change goal, 36 (59%) versus. 23 (40%), p = 0.005. Regardless of training status, physical activity, screen time, and weight status were assessed for most patients, and most were satisfied with the discussion. Few (21%) were asked about barriers to behavior change.

In ultrarare cases, patients vaccinated with DNA adenovirus vector vaccine against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), develop a vaccine-induced immune thrombotic thrombocytopenia (VITT), with a high incidence of fatal cases. The causative agent is the development of platelet factor 4 (PF4)-dependent antibodies that resemble heparin-induced thrombocytopenia (HIT) complication, although many differences can be noticed in clinical presentation, antibody reactivity, involved epitopes on the PF4 protein, and pathological mechanisms. From the literature review, and the experience of HIT and testing a few plasmas from patients with VITT, this review analyzes the possible mechanisms, which show the strong immunoglobulin G (IgG) antibody reactivity to PF4 alone, in the absence of heparin, and to a lesser extend to stoichiometric complexes of PF4 and heparin (H-PF4). In addition, much lower heparin concentrations are required for inhibiting antibody binding to PF4. These concentrations are much lower than those required for disrupting the stoichiometric H-PF4 complexes. This confirms that IgG antibodies responsible for HIT bind preferentially to PF4, to epitopes that are readily masked by low concentrations of heparin. These antibodies are at a much higher concentration than the current ones observed for HIT, keeping a strong reactivity even for plasma dilutions as high as 1/500 to 1/5,000, whilst the current dilution for testing heparin-dependent antibodies in HIT is 1/100. Although VITT anti-PF4 antibodies can be detected with the current anti-H-PF4 enzyme-linked immunosorbent assays (ELISAs) designed for HIT, some assays have low sensitivity or are unreactive, like lateral immunofiltration methods or chemiluminescent automated assays. The preferred method should concern the use of capture assays using PF4 coated solid surfaces. This report proposes that the immune response is only targeted to the binding domain of PF4 with the hexons present on the adenovirus vector, through an epitope spreading mechanism, without any exposure of neo-epitopes on PF4 protein.

Designing biocompatible and flexible electronic devices for neuromrophic applications remains a challenge. Here, Kireev et al. propose graphene-based artificial synaptic transistors with low-energy switching, long-term potentiation, and metaplasticity for future bio-interfaced neural networks.

Abstract Background Food prepared out-of-home is typically energy-dense and nutrient-poor. This food can be purchased from multiple types of retailer, including restaurants and takeaway food outlets. Using online food delivery services to purchase food prepared out-of-home is increasing in popularity. This may lead to more frequent unhealthy food consumption, which is positively associated with poor diet and living with obesity. Understanding possible reasons for using online food delivery services might contribute to the development of future public health interventions, if deemed necessary. This knowledge would be best obtained by engaging with individuals who use online food delivery services as part of established routines. Therefore, we aimed to investigate customer experiences of using online food delivery services to understand their reasons for using them, including any advantages and drawbacks. Methods and results In 2020, we conducted telephone interviews with 22 adults living in the UK who had used online food delivery services on at least a monthly basis over the previous year. Through codebook thematic analysis, we generated five themes: ‘The importance of takeaway food’, ‘Less effort for more convenience’, ‘Saving money and reallocating time’, ‘Online food delivery service normalisation’ and ‘Maintained home food practices’. Two concepts were overarching throughout: ‘Place. Time. Situation.’ and ‘Perceived advantages outweigh recognised drawbacks’. After considering each of the accessible food purchasing options within the context of their location and the time of day, participants typically selected online food delivery services. Participants reported that they did not use online food delivery services to purchase healthy food. Participants considered online food delivery service use to be a normal practice that involves little effort due to optimised purchasing processes. As a result, these services were seen to offer convenient access to food aligned with sociocultural expectations. Participants reported that this convenience was often an advantage but could be a drawback. Although participants were price-sensitive, they were willing to pay delivery fees for the opportunity to complete tasks whilst waiting for delivery. Furthermore, participants valued price-promotions and concluded that receiving them justified their online food delivery service use. Despite takeaway food consumption, participants considered home cooking to be irreplaceable. Conclusions Future public health interventions might seek to increase the healthiness of food available online whilst maintaining sociocultural values. Extending restrictions adopted in other food environments to online food delivery services could also be explored.

IntroductionBurkholderia thailandensis is a study model for Burkholderia pseudomallei, a highly virulent pathogen, known to be the causative agent of melioidosis and a potential bioterrorism agent. These two bacteria use an (acyl-homoserine lactone) AHL-mediated quorum sensing (QS) system to regulate different behaviors including biofilm formation, secondary metabolite productions, and motility.MethodsUsing an enzyme-based quorum quenching (QQ) strategy, with the lactonase SsoPox having the best activity on B. thailandensis AHLs, we evaluated the importance of QS in B. thailandensis by combining proteomic and phenotypic analyses.ResultsWe demonstrated that QS disruption largely affects overall bacterial behavior including motility, proteolytic activity, and antimicrobial molecule production. We further showed that QQ treatment drastically decreases B. thailandensis bactericidal activity against two bacteria (Chromobacterium violaceum and Staphylococcus aureus), while a spectacular increase in antifungal activity was observed against fungi and yeast (Aspergillus niger, Fusarium graminearum and Saccharomyces cerevisiae).DiscussionThis study provides evidence that QS is of prime interest when it comes to understanding the virulence of Burkholderia species and developing alternative treatments.

Summary: Shared decision making for infant feeding in the context of HIV in high-resourced settings is necessary to acknowledge patient autonomy, meet increasing patient requests and address the changing reality of perinatal HIV care. In low-to middle-income countries (LMIC), where the majority of individuals living with HIV reside, persons with HIV are recommended to breastfeed their infants. In the setting of maternal anti-retroviral therapy (ART) use throughout pregnancy, viral suppression and appropriate neonatal post-exposure prophylaxis (PEP) use, updated information indicates that the risk of HIV transmission through breastmilk may be between 0.3 and 1%. While not endorsing or recommending breastfeeding, the United States’ DHHS perinatal guidelines are similarly pivoting, stating that individuals should “receive patient-centred, evidence-based counselling on infant feeding options.” Similar statements appear in the British, Canadian, Swiss, European, and Australasian perinatal guidelines. We assembled a multi-disciplinary group at our institution to develop a structured shared decision-making process and protocol for successful implementation of breastfeeding. We recommend early and frequent counselling about infant feeding options, which should include well known benefits of breastfeeding even in the context of HIV and the individual’s medical and psychosocial circumstances, with respect and support for patient’s autonomy in choosing their infant feeding option.

The purpose of this study is to demonstrate both internally and externally, that the Holy Bible is indeed the Word of God so that believers become firmer in believing it and love it more as their holy text. Christians consider the Bible to be sacred because it contains messages from God. This is very important because there are many erroneous and misleading teachings about the Bible, which teach that the Bible contains the Word of God, the Bible being the Word of God and the Bible not being the Word of God. Irrespective, believers need to follow the rules it contains for living life and can turn to the teachings of Jesus Christ for moral and the deepest spiritual guidance. The research method used by the author was a qualitative one with a systematic theology study approach, because the domain of this research is in the field of theology, specifically Systematic Theology. In proving internally that the Bible is the Word of God, the primary and only source is the Bible itself with its self-authenticating Scriptures. The Bible is in essence true because it says it is true, and it is the Holy Spirit that bears witness to its profound truths. In proving externally that the Bible is the Word of God, the sources are books. Internal proof that the Bible is the Word of God is the teaching of Jesus, the teaching of Paul, Peter and others, the teaching of important terms, and the teaching of the fulfillment of Biblical prophecy. External evidence that the Bible is the Word of God is evident through the uniqueness of the Bible and evidence through archaeological evidence (inter alia, the Dead Sea Scrolls, Nuzi Inscriptions, Ebla Inscriptions, Discovery in Mari).

Mutations in tubulin alpha 4a (TUBB4A) result in a spectrum of leukodystrophies, including Hypomyelination with atrophy of basal ganglia and cerebellum (H-ABC), resulting from a recurring mutation p.Asp249Asn (TUBB4AD249N). H-ABC presents with dystonia, motor and cognitive impairment and pathological features of hypomyelination and loss of cerebellar and striatal neurons. We have generated three induced pluripotent stem cell (iPSC) lines from fibroblast and peripheral blood mononuclear cells (PBMCs) of individuals with TUBB4AD249N mutation. The iPSCs were assessed to confirm a normal karyotype, pluripotency, and trilineage differentiation potential. The iPSCs will allow for disease modeling, understanding mechanisms and testing of therapeutic targets.