Search

ABSTRACTIntroduction Different COVID-19 vaccines are being utilized as boosters. This systematic review and meta-analysis aims to evaluate the reactogenicity of COVID-19 vaccines given as booster doses, according to vaccine type, dose, timing, participant characteristics and primary immunization regimen received.Methods Four databases (MEDLINE, Embase, Web of Science and CENTRAL) were searched for randomized controlled trials between 1 January 2020 and 1 January 2023 according to predetermined criteria.Results Twenty-eight studies describing 19 vaccines of four different types (viral vector, inactivated, mRNA and protein sub-unit) were identified. BNT162b2 vaccine (Pfizer-BioNTech) was selected as the control as it was most often compared with other vaccines. Fever, fatigue, headache, injection-site pain, redness, and swelling were the most frequently reported solicited events. mRNA vaccines were the most reactogenic, followed by viral vector vaccines and protein sub-unit vaccines, while inactivated vaccines were the least reactogenic. Full-dose vaccines were more reactogenic than half-dose vaccines. Heterologous BNT162b2 boosters were more reactogenic than boosters with the same vaccine used for primary immunization.Conclusions COVID-19 vaccine booster schedules have distinct reactogenicity profiles, dependent on dose and vaccine type, which may allow targeted recommendations and provide choice for specific populations. Greater standardization of adverse event reporting will aid future studies.

A growing body of literature has documented the contribution of teacher-student relationship quality to both persistence and reduction in peer aggression incidents in the school context. The research literature indicates that students who are involved in peer aggression also tend to experience lower levels of closeness in their relationships with their teachers. However, these study results have not yet been aggregated, and the size and direction of effects remains unclear. In the present study we quantitatively synthesized 66 individual studies (Nstudents = 352,376) in two meta-analyses by aggregating cross-sectional associations between peer aggression involvement and teacher-student relationship closeness that have been reported in the literature over the last 20 years. A small, negative, and significant association was found between perpetration and victimization and teacher-student relationship closeness, indicating that students who experience greater involvement in peer aggression also have relationships with their teachers that are lacking in closeness. Three moderator analyses were also conducted. No moderating effect was found for school level or measure type; however, a significant moderating effect was found for informant type. The results from the meta-analyses lead to direct recommendations for practice regarding how we can best support students' psychosocial development in the school context.

Abstract Background Within China, Hepatitis B virus (HBV) infection remains widely prevalent and one of the major public health problems. There have been only two previous estimates of its prevalence at the population level in China, with the latest survey conducted in 2006. A meta-analysis estimated the prevalence of HBV within China between 2013 and 2017 as 7%. This review provides an updated estimate of HBV prevalence in China from 2018 to 2022. Methods Systematic searches of literature from January 1, 2018 to December 25, 2022 were conducted in four international databases (Medline, Web of Science, Embase, Cochrane Database of Systematic Reviews) and three Chinese databases (CNKI, CBM, and WanFang data). Random-effects meta-analyses were conducted to calculate the pooled HBV prevalence with 95% confidence intervals in the overall population and subgroups. Publication bias, heterogeneity between studies, and study quality were assessed. Results Twenty-five articles were included in the meta-analysis. The pooled prevalence of HBV infection in the Chinese general population from 2018 to 2022 was 3% (95%CI: 2–4%). The prevalence of HBV infection was similar between males and females (both 3%), while rural areas had a higher prevalence than urban areas (3% vs 2%). The highest prevalence of HBV was reported in the eastern provinces (4, 95%CI: 2–6%). The HBV prevalence of people aged ≥18 years old (6, 95%CI: 4–8%) was higher than people aged

With the exception of ApoE4, genome-wide association studies have failed to identify strong genetic risk factors for late-onset Alzheimer's disease, despite strong evidence of heritability, suggesting that many low penetrance genes may be involved. Additionally, the nature of the identified genetic risk factors and their relation to disease pathology is also largely obscure. Previous studies have found that a cancer-associated variant of the cell cycle inhibitor gene p21cip1 is associated with increased risk of Alzheimer's disease. The aim of this study was to confirm this association and to elucidate the effects of the variant on protein function and Alzheimer-type pathology. We examined the association of the p21cip1 variant with Alzheimer's disease and Parkinson's disease with dementia. The genotyping studies were performed on 719 participants of the Oxford Project to Investigate Memory and Ageing, 225 participants of a Parkinson's disease DNA bank, and 477 participants of the Human Random Control collection available from the European Collection of Cell Cultures. The post mortem studies were carried out on 190 participants. In the in-vitro study, human embryonic kidney cells were transfected with either the common or rare p21cip1 variant; and cytometry was used to assess cell cycle kinetics, p21cip1 protein expression and sub-cellular localisation. The variant was associated with an increased risk of Alzheimer's disease, and Parkinson's disease with dementia, relative to age matched controls. Furthermore, the variant was associated with an earlier age of onset of Alzheimer's disease, and a more severe phenotype, with a primary influence on the accumulation of tangle pathology. In the in-vitro study, we found that the SNPs reduced the cell cycle inhibitory and anti-apoptotic activity of p21cip1. The results suggest that the cancer-associated variant of p21cip1 may contribute to the loss of cell cycle control in neurons that may lead to Alzheimer-type neurodegeneration.

Disease modifying treatments for Alzheimer's disease (AD) constitute a major goal in medicine. Current trends suggest that biomarkers reflective of AD neuropathology and modifiable by treatment would provide supportive evidence for disease modification. Nevertheless, a lack of quantitative tools to assess disease modifying treatment effects remains a major hurdle. Cerebrospinal fluid (CSF) biochemical markers such as total tau, p-tau and Ab42 are well established markers of AD; however, global quantitative biochemical changes in CSF in AD disease progression remain largely uncharacterized. Here we applied a high resolution open discovery platform, dMS, to profile a cross-sectional cohort of lumbar CSF from post-mortem diagnosed AD patients versus those from non-AD/non-demented (control) patients. Multiple markers were identified to be statistically significant in the cohort tested. We selected two markers SME-1 (p

ABSTRACTThe COVID-19 pandemic disproportionately affected racial and ethnic minority communities across the United States (U.S.). Despite the disproportionate burden of COVID-19 faced by communities of color, Black and Hispanic communities are less likely to be fully vaccinated than White non-Hispanic Persons. Health inequity and vaccine hesitancy are complex phenomena that require multilevel responses tailored to the unique needs of each community, a process that inherently necessitates a high level of community engagement in order to develop the most effective health interventions. Building on the principles of community based participatory research (CBPR) and with the support of the National Institutes of Health (NIH), Project 2VIDA! was born. A multidisciplinary collaborative of academic researchers, community members, and clinicians whose aim is to foster sustainable partnerships to reduce the burden of COVID-19 in Hispanic and Black communities across Southern California. Our model was designed to meet our community members where they were – whether on their lunch break or picking their children from school. This CBPR model has been well received by community members. Future health interventions focused on reducing health disparities should prioritize the role of the community, leverage the voices of key community partners, and be grounded in equitable power sharing.

Objectives: The accuracy of malaria rapid diagnostic tests is threatened by Plasmodium falciparum with pfhrp2/3 deletions. This study compares gene deletion prevalence determined by multiplex real time polymerase chain reaction (qPCR) and conventional polymerase chain reaction (cPCR) using existing samples with clonality previously determined by microsatellite genotyping. Methods: Multiplex qPCR was used to estimate prevalence of pfhrp2/3 deletions in three sets of previously collected patient samples from Eritrea and Peru. The qPCR was validated by multiplex digital polymerase chain reaction. Sample classification was compared with cPCR, and receiver operating characteristic curve analysis was used to determine the optimal ΔCq threshold that aligned the results of the two assays. Results: qPCR classified 75% (637 of 849) of samples as single, and 212 as mixed-pfhrp2/3 genotypes, with a positive association between clonality and proportion of mixed-pfhrp2/3 genotype samples. The sample classification agreement between cPCR and qPCR was 75.1% (95% confidence interval [CI] 68.6-80.7%) and 47.8% (95% CI 38.9-56.9%) for monoclonal and polyclonal infections. The qPCR prevalence estimates of pfhrp2/3 deletions showed almost perfect (κ = 0.804, 95% CI 0.714-0.895) and substantial agreement (κ = 0.717, 95% CI 0.562-0.872) with cPCR for Peru and 2016 Eritrean samples, respectively. For 2019 Eritrean samples, the prevalence of double pfhrp2/3 deletions was approximately two-fold higher using qPCR. The optimal threshold for matching the assay results was ΔCq = 3. Conclusions: Multiplex qPCR and cPCR produce comparable estimates of gene deletion prevalence when monoclonal infections dominate; however, qPCR provides higher estimates where multi-clonal infections are common.

Prostate cancer (PCa) appears among the most frequently diagnosed types of malignancies in males. Because of the high demand and increasing detection rate of early PCa, alongside the specificity limitations of the gold standard clinical tools available for the diagnosis and prognosis of prostate cancer, there is an urgent need for more reliable PCa markers and highly sensitive diagnostic tools to avoid under-treatment and over-diagnosis. PCA3, or prostate cancer antigen 3, is a potential prostate cancer biomarker that is more specific and useful for preventing unnecessary repeat biopsies, particularly in men with persistently high prostate-specific antigen indices after a negative biopsy. Additionally, an electrochemically based biosensor would prove to be a powerful diagnostic tool for PCA3 detection in urine because of its simplicity, sensitivity, and cost-effectiveness, in contrast to the more traditional PCa diagnostics that depend on blood testing. This paper aimed to design a novel and simple electrochemical impedimetric biosensor based on a label-free RNA-aptamer (CG3-PCA3) as the molecular recognition element for detecting PCA3. The proposed aptasensor for the detection of PCA3 has been developed using a screen-printed carbon electrode (SPCE) modified by gold nanoparticles (AuNPs), further improving sensitivity and allowing the immobilisation of thiolate aptamers on its surface. The findings presented here demonstrated a high sensitivity to PCA3, with a detection limit of 20 fM in artificial urine and 1 fM in buffer. These results indicate that the PCA3 aptasensor could be a promising tool for routine PCa diagnosis due to its high sensitivity and cost-effectiveness.

Abstract Background Rapid diagnostic tests (RDTs) that detect Plasmodium falciparum histidine-rich protein-2 (PfHRP2) are exclusively deployed in Uganda, but deletion of the pfhrp2/3 target gene threatens their usefulness as malaria diagnosis and surveillance tools. Methods A cross-sectional survey was conducted at 40 sites across four regions of Uganda in Acholi, Lango, W. Nile and Karamoja from March 2021 to June 2023. Symptomatic malaria suspected patients were recruited and screened with both HRP2 and pan lactate dehydrogenase (pLDH) detecting RDTs. Dried blood spots (DBS) were collected from all patients and a random subset were used for genomic analysis to confirm parasite species and pfhrp2 and pfhrp3 gene status. Plasmodium species was determined using a conventional multiplex PCR while pfhrp2 and pfhrp3 gene deletions were determined using a real-time multiplex qPCR. Expression of the HRP2 protein antigen in a subset of samples was further assessed using a ELISA. Results Out of 2435 symptomatic patients tested for malaria, 1504 (61.8%) were positive on pLDH RDT. Overall, qPCR confirmed single pfhrp2 gene deletion in 1 out of 416 (0.2%) randomly selected samples that were confirmed of P. falciparum mono-infections. Conclusion These findings show limited threat of pfhrp2/3 gene deletions in the survey areas suggesting that HRP2 RDTs are still useful diagnostic tools for surveillance and diagnosis of P. falciparum malaria infections in symptomatic patients in this setting. Periodic genomic surveillance is warranted to monitor the frequency and trend of gene deletions and its effect on RDTs.

The popularization of intelligent healthcare devices and big data analytics significantly boosts the development of Smart Healthcare Networks (SHNs). To enhance the precision of diagnosis, different participants in SHNs share health data that contain sensitive information. Therefore, the data exchange process raises privacy concerns, especially when the integration of health data from multiple sources (linkage attack) results in further leakage. Linkage attack is a type of dominant attack in the privacy domain, which can leverage various data sources for private data mining. Furthermore, adversaries launch poisoning attacks to falsify the health data, which leads to misdiagnosing or even physical damage. To protect private health data, we propose a personalized differential privacy model based on the trust levels among users. The trust is evaluated by a defined community density, while the corresponding privacy protection level is mapped to controllable randomized noise constrained by differential privacy. To avoid linkage attacks in personalized differential privacy, we design a noise correlation decoupling mechanism using a Markov stochastic process. In addition, we build the community model on a blockchain, which can mitigate the risk of poisoning attacks during differentially private data transmission over SHNs. Extensive experiments and analysis on real-world datasets have testified the proposed model, and achieved better performance compared with existing research from perspectives of privacy protection and effectiveness.

Prior to the introduction of COVID-19 vaccines, patients with severe mental illness (SMI) were at greater risk of COVID-19-related outcomes than the general population. It is not yet clear whether COVID-19 vaccines have reduced the risk gap. We systematically searched nine international databases and three Chinese databases to identify relevant studies from December 2020 to December 2023 to compare the risk of COVID-19-related outcomes for SMI patients to those without SMI after vaccination. Random effects meta-analysis was performed to estimate the pooled odds ratio (OR) with 95% confidence intervals (CI). Subgroup analysis, sensitivity analysis, and publication bias analysis were conducted with R software 4.3.0. A total of 11 observational studies were included. Compared with controls, SMI patients were associated with a slightly increased risk of infection (pooled OR = 1.10, 95% CI, 1.03–1.17, I2 = 43.4%), while showing a 2-fold higher risk of hospitalization (pooled OR = 2.66, 95% CI, 1.13–6.22, I2 = 99.6%), even after both groups have received COVID-19 vaccines. Limited evidence suggests a higher mortality risk among SMI patients compared to controls post vaccination, but the findings did not reach statistical significance. SMI patients remain at increased risk compared to their peers in COVID-19-related outcomes even after vaccination. Vaccination appears an effective approach to prevent severe COVID-19 illness in SMI patients, and actions should be taken by healthcare providers to improve vaccination coverage in these vulnerable groups.

Manufacturing management and operations place heavy emphasis on monitoring and improving production performance. This supervision is accomplished through strategies of manufacturing performance management, a set of measurements and methods used to monitor production conditions. Over the last 30 years, the most prevalent measurement of traditional performance management has been overall equipment effectiveness, a percentile summary metric of a machine’s utilization. The technologies encapsulated by Industry 4.0 have expanded the ability to gather, process, and store vast quantities of data, creating the opportunity to innovate on how performance is measured. A new method of managing manufacturing performance utilizing Industry 4.0 technologies has been proposed by McKinsey & Company (New York City, NY, USA), and software tools have been developed by PTC Inc. (Boston, MA, USA) to aid in performing what they both call digital performance management. To evaluate this new approach, the digital performance management tool was deployed on a Festo (Esslingen, Germany) Cyber-Physical Lab (FCPL), an educational mock production environment, and compared to a digitally enabled traditional performance management solution. Results from a multi-day production period displayed an increased level of detail in both the data presented to the user and the insights gained from the digital performance management solution as compared to the traditional approach. The time unit measurements presented by digital performance management paint a clear picture of what and where losses are occurring during production and the impact of those losses. This is contrasted by the single summary metric of a traditional performance management approach, which easily obfuscates the constituent data and requires further investigation to determine what and where production losses are occurring.

Vitamin B-12 is essential for the development and maintenance of a healthy nervous system. Brain development occurs primarily in utero and early infancy, but the role of maternal vitamin B-12 status during pregnancy on offspring cognitive function is unclear. In this study we assessed the effect of vitamin B-12 status in well-nourished pregnant women on the cognitive ability of their offspring in a UK birth cohort (ALSPAC). We then examined the association of SNPs in maternal genes FUT2 (rs492602) and TCN2 (rs1801198, rs9606756) that are related to plasma vitamin B-12, with offspring IQ. Observationally, there was a positive association between maternal vitamin B-12 intake and child's IQ that was markedly attenuated after adjustment for potential confounders (mean difference in offspring IQ score per doubling of maternal B-12 intake, before adjustment: 2.0 (95% CI 1.3, 2.8); after adjustment: 0.7 (95% CI -0.04, 1.4)). Maternal FUT2 was weakly associated with offspring IQ: mean difference in IQ per allele was 0.9 (95% CI 0.1, 1.6). The expected effect of maternal vitamin B-12 on offspring IQ, given the relationships between SNPs and vitamin B-12, and SNPs and IQ was consistent with the observational result. Our findings suggest that maternal vitamin B-12 may not have an important effect on offspring cognitive ability. However, further examination of this issue is warranted.

BackgroundLate Onset Alzheimer's disease (LOAD) is the leading cause of dementia. Recent large genome-wide association studies (GWAS) identified the first strongly supported LOAD susceptibility genes since the discovery of the involvement of APOE in the early 1990s. We have now exploited these GWAS datasets to uncover key LOAD pathophysiological processes.MethodologyWe applied a recently developed tool for mining GWAS data for biologically meaningful information to a LOAD GWAS dataset. The principal findings were then tested in an independent GWAS dataset.Principal findingsWe found a significant overrepresentation of association signals in pathways related to cholesterol metabolism and the immune response in both of the two largest genome-wide association studies for LOAD.SignificanceProcesses related to cholesterol metabolism and the innate immune response have previously been implicated by pathological and epidemiological studies of Alzheimer's disease, but it has been unclear whether those findings reflected primary aetiological events or consequences of the disease process. Our independent evidence from two large studies now demonstrates that these processes are aetiologically relevant, and suggests that they may be suitable targets for novel and existing therapeutic approaches.

An increased rate of brain atrophy is often observed in older subjects, in particular those who suffer from cognitive decline. Homocysteine is a risk factor for brain atrophy, cognitive impairment and dementia. Plasma concentrations of homocysteine can be lowered by dietary administration of B vitamins.To determine whether supplementation with B vitamins that lower levels of plasma total homocysteine can slow the rate of brain atrophy in subjects with mild cognitive impairment in a randomised controlled trial (VITACOG, ISRCTN 94410159).Single-center, randomized, double-blind controlled trial of high-dose folic acid, vitamins B(6) and B(12) in 271 individuals (of 646 screened) over 70 y old with mild cognitive impairment. A subset (187) volunteered to have cranial MRI scans at the start and finish of the study. Participants were randomly assigned to two groups of equal size, one treated with folic acid (0.8 mg/d), vitamin B(12) (0.5 mg/d) and vitamin B(6) (20 mg/d), the other with placebo; treatment was for 24 months. The main outcome measure was the change in the rate of atrophy of the whole brain assessed by serial volumetric MRI scans.A total of 168 participants (85 in active treatment group; 83 receiving placebo) completed the MRI section of the trial. The mean rate of brain atrophy per year was 0.76% [95% CI, 0.63-0.90] in the active treatment group and 1.08% [0.94-1.22] in the placebo group (P = 0.001). The treatment response was related to baseline homocysteine levels: the rate of atrophy in participants with homocysteine >13 µmol/L was 53% lower in the active treatment group (P = 0.001). A greater rate of atrophy was associated with a lower final cognitive test scores. There was no difference in serious adverse events according to treatment category.The accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine-lowering B vitamins. Sixteen percent of those over 70 y old have mild cognitive impairment and half of these develop Alzheimer's disease. Since accelerated brain atrophy is a characteristic of subjects with mild cognitive impairment who convert to Alzheimer's disease, trials are needed to see if the same treatment will delay the development of Alzheimer's disease.Controlled-Trials.com ISRCTN94410159.

BACKGROUND:The insulin-degrading enzyme gene (IDE) is a strong functional and positional candidate for late onset Alzheimer's disease (LOAD). METHODOLOGY/PRINCIPAL FINDINGS:We examined conserved regions of IDE and its 10 kb flanks in 269 AD cases and 252 controls thereby identifying 17 putative functional polymorphisms. These variants formed eleven haplotypes that were tagged with ten variants. Four of these showed significant association with IDE transcript levels in samples from 194 LOAD cerebella. The strongest, rs6583817, which has not previously been reported, showed unequivocal association (p = 1.5x10(-8), fold-increase = 2.12,); the eleven haplotypes were also significantly associated with transcript levels (global p = 0.003). Using an in vitro dual luciferase reporter assay, we found that rs6583817 increases reporter gene expression in Be(2)-C (p = 0.006) and HepG2 (p = 0.02) cell lines. Furthermore, using data from a recent genome-wide association study of two Croatian isolated populations (n = 1,879), we identified a proxy for rs6583817 that associated significantly with decreased plasma Abeta40 levels (ss = -0.124, p = 0.011) and total measured plasma Abeta levels (b = -0.130, p = 0.009). Finally, rs6583817 was associated with decreased risk of LOAD in 3,891 AD cases and 3,605 controls. (OR = 0.87, p = 0.03), and the eleven IDE haplotypes (global p = 0.02) also showed significant association. CONCLUSIONS:Thus, a previously unreported variant unequivocally associated with increased IDE expression was also associated with reduced plasma Abeta40 and decreased LOAD susceptibility. Genetic association between LOAD and IDE has been difficult to replicate. Our findings suggest that targeted testing of expression SNPs (eSNPs) strongly associated with altered transcript levels in autopsy brain samples may be a powerful way to identify genetic associations with LOAD that would otherwise be difficult to detect.

Abstract Background Globally, COVID-19 vaccines have proven to be instrumental for promoting population health by reducing illness from SARS-CoV-2. Vaccine certificates emerged as a potentially promising solution for encouraging vaccination and facilitating the safe reopening of society, however, they were controversial due to criticisms of infringing upon individual rights. While there is extensive literature describing the ethical, legal, and public health implications of vaccine certificates, there is currently a gap in knowledge about the association of vaccine certificates on vaccine uptake during the COVID-19 pandemic and barriers and facilitators to their use. Objectives The objectives of this scoping review are to (i) describe the existing literature on the association of vaccine certificates on the rates of COVID-19 vaccine uptake across several countries and (ii) describe the intrinsic and extrinsic barriers or facilitators that moderate this relationship. Methods We conducted a scoping review based on PRISMA Extension for Scoping Reviews (PRSIMA-ScR) guidelines. We searched three bibliographic databases (APA PsychInfo, Embase Classic + Embase, OVID-Medline) and preprint severs during the first week of July 2023. Three reviewers independently screened the studies based on pre-specified eligibility criteria and performed quality assessments of the primary literature and data extraction. Results Sixteen studies met the inclusion criteria. 14 or these were surveys and 2 were modelling studies. The majority documented that vaccine certificates were significantly associated with increased rates of COVID-19 vaccine uptake (n = 12), motivated by factors such as travel/employer requirements, influence from the government/peers, and trust in the safety, efficacy, and science behind COVID-19 vaccines. Three studies had non-significant or mixed findings. Only one study found a significant decrease in COVID-19 vaccine uptake, motivated by pervasive distrust in the QR code-based system of digital vaccine certificates in Russia. Quality of survey studies was generally high. Conclusion Our findings provide insights into the existing literature on vaccine certificates association with vaccine uptake in several different jurisdictions and barriers and facilitators to their uptake. This information can be used to guide future examinations of the implementation of vaccine certificates and more effective implementations.

Malamides (diamide derivatives of malic acid) are prevalent in nature and of significant biological interest, yet only limited synthetic methods to access functionalised enantiopure derivatives have been established to date. Herein, an effective synthetic method to generate this molecular class is developed through in situ formation of spirocyclic β-lactone-oxindoles (employing a known enantioselective isothiourea-catalysed formal [2+2] cycloaddition of C(1)-ammonium enolates and isatin derivatives) followed by a subsequent dual ring-opening protocol (of the β-lactone and oxindole) with amine nucleophiles. The application of this protocol is demonstrated across twelve examples to give densely functionalised malamide derivatives with high enantio- and diastereo-selectivity (up to >95:5 dr and >99:1 er).

Like the majority of non-communicable diseases that have recently gained attention, functional gastrointestinal (GI) disorders (FGID) in both children and adults are caused by a variety of medical conditions. In general, while it is often thought that common conditions such as obesity may cause other problems, for example, asthma or mental health issues, more consideration needs to be given to the possibility that they could both be brought on by a single underlying problem. Based on the variations in non-communicable disease, in recent years, our group has been revisiting the exact role of the intestinal microbiome within the Vertebrata. While the metabolic products of the microbiome have a role to play in the adult, our tentative conclusion is that the fully functioning, mutualistic microbiome has a primary role: to transfer antigen information from the mother to the neonate in order to calibrate its immune system, allowing it to survive within the microbial environment into which it will emerge. Granted that the microbiome possesses such a function, logic suggests the need for a robust, flexible, mechanism allowing for the partition of nutrition in the mature animal, thus ensuring the continued existence of both the vertebrate host and microbial guest, even under potentially unfavourable conditions. It is feasible that this partition process acts by altering the rate of peristalsis following communication through the gut–brain axis. The final step of this animal–microbiota symbiosis would then be when key microbes are transferred from the female to her progeny, either live offspring or eggs. According to this scheme, each animal inherits twice, once from its parents’ genetic material and once from the mother’s microbiome with the aid of the father’s seminal microbiome, which helps determine the expression of the parental genes. The key point is that the failure of this latter inheritance in humans leads to the distinctive manifestations of functional FGID disorders including inflammation and gut motility disturbances. Furthermore, it seems likely that the critical microbiome–gut association occurs in the first few hours of independent life, in a process that we term handshaking. Note that even if obvious disease in childhood is avoided, the underlying disorders may intrude later in youth or adulthood with immune system disruption coexisting with gut–brain axis issues such as excessive weight gain and poor mental health. In principle, investigating and perhaps supplementing the maternal microbiota provide clinicians with an unprecedented opportunity to intervene in long-term disease processes, even before the child is born.

Coral carbonate production is fundamental to reef accretion and, consequently, the preservation of essential reef ecosystem services, such as wave attenuation and sustained reef biodiversity. However, the unprecedented loss of coral reefs from anthropogenic impacts has put these valuable ecosystem services at risk. To counteract this loss, active rehabilitation of degraded reef sites has accelerated globally. A variety of restoration practices exist, tailored to local site needs and reef types. For sites where there is a significant unconsolidated substrate, Mars Assisted Reef Restoration System (MARRS, or “Reef Stars”) has been utilised to contribute toward rubble stabilisation and reef accretion. However, the effect of the Reef Stars on the local carbonate budgets and structural complexity has not been assessed. For that purpose, we assess coral cover and reef complexity through a census-based approach to identify the contribution of carbonate producers and eroders alongside studying coral skeletal properties to estimate current carbonate budgets on a rehabilitated site compared to natural unrehabilitated reef and rubble patches on the mid-Great Barrier Reef. Our research identified positive ecological processes and ecological functions such as increased carbonate budget, coral cover and structural complexity at the restored site compared to the non-intervened reef and rubble patches. In general, no impacts on skeletal rigour relative to this active reef restoration were found for two key coral species and the Acropora rubble for most of the skeletal traits. However, Pocillopora damicornis hardness seemed to decrease on the restored site compared to the other sites, demonstrating different performances of coral species during restoration activities that should be considered to maximise return-on-effort of restoration activities. Overall, our data demonstrate that consideration of carbonate budgets is important for measuring success of coral restoration initiatives and that coral restoration can be a relevant tool to recover lost local carbonate budgets.

The goal of this project is to survey attorney perceptions of social workers. This will lead to suggestions on how social workers can be more effectively integrated into the courtroom and legal system as well as to suggestions for further study. This goal reflects Person-In-Environment theory by highlighting the importance of attorneys needing to understand the contextual variables social workers can explain to the court, thereby explaining what social, political, and economic issues may have caused a client to be involved in crime in the first place. This goal also reflects Holistic Defense Theory by ensuring that clients legal and social needs are met by highlighting the need for both attorneys and social workers as part of the defense team. Lastly, this project may contribute to making justice in the courtroom reachable for traditionally disaffected people who can be made whole again by legal and social intervention.

Introduction Severe aortic stenosis is a major cause of morbidity and mortality. The existing treatment pathway for transcatheter aortic valve implantation (TAVI) traditionally relies on tertiary Heart Valve Centre workup. However, this has been associated with delays to treatment, in breach of British Cardiovascular Intervention Society targets. A novel pathway with emphasis on comprehensive patient workup at a local centre, alongside close collaboration with a Heart Valve Centre, may help reduce the time to TAVI.Methods The centre performing local workup implemented a novel TAVI referral pathway. Data were collected retrospectively for all outpatients referred for consideration of TAVI to a Heart Valve Centre from November 2020 to November 2021. The main outcome of time to TAVI was calculated as the time from Heart Valve Centre referral to TAVI, or alternative intervention, expressed in days. For the centre performing local workup, referral was defined as the date of multidisciplinary team discussion. For this centre, a total pathway time from echocardiographic diagnosis to TAVI was also evaluated. A secondary outcome of the proportion of referrals proceeding to TAVI at the Heart Valve Centre was analysed.Results Mean±SD time from referral to TAVI was significantly lower at the centre performing local workup, when compared with centres with traditional referral pathways (32.4±64 to 126±257 days, p

This paper explores new methods for disambiguating the identity of individuals in classical Arabic citations (isnāds) using a network-based approach. After training a model to extract name mentions from classical Arabic, we embed these mentions in vector space using fine-tuned BERT representations and use community detection to infer clusters of coreferent mentions. The best-performing clustering approach reduces error on the CoNLL metric by 30%. Then, as a case study, we examine the problem of determining the number of direct transmitters to Ibn ʿAsākir (d. 1176) in a set of isnāds taken from the 12th century historical text Taʾrīkh Madīnat Dimashq (TMD, History of Damascus), using our method to replicate human judgement.

Vaccine certificates have been implemented worldwide, aiming to promote vaccination rates and to reduce the spread of COVID-19. However, their use during the COVID-19 pandemic was controversial and has been criticized for infringing upon medical autonomy and individual rights. We administered a national online survey exploring social and demographic factors predicting the degree of public approval of vaccine certificates in Canada. We conducted a multivariate linear regression which revealed which factors were predictive of vaccine certificate acceptance in Canada. Self-reported minority status (p

The literatures on global commodity chains and global value chains rest on an unquestioned assumption: the continual expansion of globalization. The Trump Administration's trade wars challenged this foundational assumption and even today the new Biden regime also hints at the shift away from global supply chains. We find that the prior administration’s efforts caused continued disruption of long-established commodity chains in steel, aluminum, automobiles, and other manufactured products. Flows of raw materials, intermediate products and components, and finished goods now confront higher costs. Firms continue efforts to restructure commodity chains in ways that will require the disarticulation of some nodes and the creation of new nodes. We claim that these trade wars and breakdown of global commodity chains (GCCs) may in fact mark the start of the breakdown of the U.S.-led world order. This shift harkens the onset of a new era of economic and geopolitical conflict. A key question: has this disruption of old patterns and rise of new ones continued in the post-Trump era? Does the familiar pattern of globalization continue – or is competition, contestation and disarticulation leading to sectoral economic changes that drive larger patterns of economic ascent, dominance, and decline in the world economy?

In the quest for the development of accurate, reliable, and cost-effective biosensing technology for early diagnostics of prostate cancer, we describe here an electrochemical biosensor combining a simple transducing method of differential pulse voltammetry (DPV) with an RNA-based aptamer labelled with a methylene blue redox group acting as a highly specific bioreceptor to the prostate cancer biomarker PCA3. A series of DPV measurements on screen-printed gold electrodes is functionalised with a redox-labelled aptamer in solutions (either buffer or synthetic urine) containing PCA3 in a wide range of concentrations from 0.1 picomolar (pM) to 10 nanomolar (nM). In these measurements, the current peak values correlate with the concentration of PCA3 and yield a low detection limit (LDL) of 0.1 pM. Furthermore, the binding kinetics study revealed the high affinity of the aptamer to the target PCA3 with the affinity constants KD of about 3.0 × 10−8 molar. In addition, the AFM study showed the increase in the molecular layer roughness caused by the binding of PCA3, which is a large RNA molecular fragment.

Objectives: Characterizing the psychometric attributes of the Persian variant of partners in health (PIH) in multiple sclerosis (MS), Diabetes, and Low Back Pain (LBP) patients. Methods: In this cross-sectional study, 183 MS, diabetes, and LBP patients (70 male, 113 female) were treated with PIH post-forward-backward translation. Confirmatory factor analysis was used for studying the factor structure. Cronbach’s α and McDonald’s Ω coefficients were used to analyze PIH internal consistency. We used an interclass correlation coefficient to evaluate test-retest reliability. Criterion validity was determined by studying the correlation of PIH and Short Form (36) Health Survey (SF-36), Diabetes Self-Management Scale (DSMS), and Self-Efficacy in Chronic Disease Self-Management (SES6G). Results: The median age of the participants was 49.73±15.16 years, 113 (61.75%) of them were female, 64 (35.0%) had MS, 66 (36.1%) had diabetes, and 53 (29.0%) had LBP. Content validity was determined across all areas (clarity, relevancy, simplicity) by a content validity index ≥0.82. Additionally, all items were confirmed via a content validity ratio ≥0.78. The outcome of CFA depicts that the statistics presented as model fit were as follows: CFI= 0.938, NFI= 0.899, and RMSEA= 0.085. All PIH items exhibited valid internal consistency (0.886-0.893). The PIH showed sufficient test-retest reliability regarding its corresponding subscales (0.554-0.679). The construct validity was confirmed by the total scores of PIH correlated with the total score of SF-36, SES6G, and DSMS. Discussion: The Persian variant of the PIH showed sufficient validity and reliability as a measure to assess self-management in patients suffering from chronic disease (MS, diabetes, and LBP).

While the importance of the intestinal microbiome has been realised for a number of years, the significance of the phrase microbiota–gut–brain axis is only just beginning to be fully appreciated. Our recent work has focused on the microbiome as if it were a single entity, modifying the expression of the genetic inheritance of the individual by the generation of interkingdom signalling molecules, semiochemicals, such as dopamine. In our view, the purpose of the microbiome is to convey information about the microbial environment of the mother so as to calibrate the immune system of the new-born, giving it the ability to distinguish harmful pathogens from the harmless antigens of pollen, for example, or to help distinguish self from non-self. In turn, this requires the partition of nutrition between the adult and its microbiome to ensure that both entities remain viable until the process of reproduction. Accordingly, the failure of a degraded microbiome to interact with the developing gut of the neonate leads to failure of this partition in the adult: to low faecal energy excretion, excessive fat storage, and concomitant problems with the immune system. Similarly, a weakened gut–brain axis distorts interoceptive input to the brain, increasing the risk of psychiatric diseases such as autism. These effects account for David Barker’s 1990 suggestion of “the fetal and infant origins of adult disease”, including schizophrenia, and David Strachan’s 1989 observation of childhood immune system diseases, such as hay fever and asthma. The industrialisation of modern life is increasing the intensity and scale of these physical and psychiatric diseases and it seems likely that subclinical heavy metal poisoning of the microbiome contributes to these problems. Finally, the recent observation of Harald Brüssow, that reported intestinal bacterial composition does not adequately reflect the patterns of disease, would be accounted for if microbial eukaryotes were the key determinant of microbiome effectiveness. In this view, the relative success of “probiotic” bacteria is due to their temporary immune system activation of the gut–brain axis, in turn suggesting a potential mechanism for the placebo effect.

Abstract Peru was the first country where pfhrp2 and pfhrp3 gene deletions were detected despite the fact that rapid diagnostics tests are not commonly used for confirmatory malaria diagnosis. This context provides a unique scenario to study the dynamics of pfhrp2 and pfhrp3 gene deletions without apparent RDTs selection pressure. In this study we characterized the presence of pfhrp2 and pfhrp3 genes on 325 P. falciparum samples collected in Iquitos and surrounding communities between 2011 and 2018 in order to understand the dynamics of gene deletion prevalence, potential associations with clinical symptomatology and parasite genetic background. P. falciparum presence was confirmed by microscopy and PCR of 18 s rRNA, pfmsp1 and pfmsp2. Gene deletions were assessed by amplification of exon1 and exon2 of pfhrp2 and pfhrp3 using gene specific PCRs. Confirmation of absence of HRP2 expression was assessed by ELISA of HRP2 and pLDH. Genotyping of 254 samples were performed using a panel of seven neutral microsatellite markers. Overall, pfhrp2 and pfhrp3 dual gene deletions were detected in 67% (217/324) parasite samples. Concordance between pfhrp2 deletion and negligible HRP2 protein levels was observed (Cohen's Kappa = 0.842). Prevalence of gene deletions was heterogeneous across study sites (adjusted p