Objectives/Goals: Transmission-blocking vaccines hold promise for malaria elimination by reducing community transmission. But a major challenge that limits the development of efficacious vaccines is the vast parasite’s genetic diversity. This work aims to assess the genetic diversity of the Pfs25 vaccine candidate in complex infections across African countries. Methods/Study Population: We employed next-generation amplicon deep sequencing to identify nonsynonymous single nucleotide polymorphisms (SNPs) in 194 Plasmodium falciparum samples from four endemic African countries: Senegal, Tanzania, Ghana, and Burkina Faso. The individuals aged between 1 and 74 years, but most of them ranged from 1 to 19 years, and all presented symptomatic P. falciparum infection. The genome amplicon sequencing was analyzed using Geneious software and P. falciparum 3D7 as a reference. The SPNs were called with a minimum coverage of 500bp, and for this work, we used a very sensitive threshold of 1% variant frequency to determine the frequency of SNPs. The identified SNPs were threaded to the crystal structure of the Pfs25 protein, which allowed us to predict the impact of the novel SNP in the protein or antibody binding. Results/Anticipated Results: We identified 26 SNPs including 24 novel variants, and assessed their population prevalence and variant frequency in complex infections. Notably, five variants were detected in multiple samples (L63V, V143I, S39G, L63P, and E59G), while the remaining 21 were rare variants found in individual samples. Analysis of country-specific prevalence showed varying proportions of mutant alleles, with Ghana exhibiting the highest prevalence (44.6%), followed by Tanzania (12%), Senegal (11.8%), and Burkina Faso (2.7%). Moreover, we categorized SNPs based on their frequency, identifying dominant variants (>25%), and rare variants (Discussion/Significance of Impact: We identified additional SNPs in the Pfs25 gene beyond those previously reported. However, the majority of these newly discovered display low variant frequency and population prevalence. Further research exploring the functional implications of these variations will be important to elucidate their role in malaria transmission.

Polygenic scores (PGSs) have garnered increasing attention in the clinical sciences due to their robust prediction signals for psychopathology, including externalizing (EXT) behaviors. However, studies leveraging PGSs have rarely accounted for the phenotypic and developmental heterogeneity in EXT outcomes. We used the National Longitudinal Study of Adolescent to Adult Health (analytic N = 4,416), spanning ages 13 to 41, to examine associations between EXT PGSs and trajectories of antisocial behaviors (ASB) and substance use behaviors (SUB) identified via growth mixture modeling. Four trajectories of ASB were identified: High Decline (3.6% of the sample), Moderate (18.9%), Adolescence-Peaked (10.6%), and Low (67%), while three were identified for SUB: High Use (35.2%), Typical Use (41.7%), and Low Use (23%). EXT PGSs were consistently associated with persistent trajectories of ASB and SUB (High Decline and High Use, respectively), relative to comparison groups. EXT PGSs were also associated with the Low Use trajectory of SUB, relative to the comparison group. Results suggest PGSs may be sensitive to developmental typologies of EXT, where PGSs are more strongly predictive of chronicity in addition to (or possibly rather than) absolute severity.

Increasing evidence indicates that (poly)phenol consumption can have beneficial effects in human brain function(1). The overall aim of this project is to investigate whether consumption of a (poly)phenol rich cranberry drink improve mental health and cognitive function in university students via the gut-brain axis.

A parallel randomised controlled trial was conducted in 72 young healthy final year university students assigned to consume 236 mL cranberry drink (442 mg polyphenols) or nutrient matched placebo, daily for 12 weeks. The primary outcome was mood, measured as Total Mood Disturbance (TMD), using the Profile of Mood States (POMS) questionnaire. Secondary outcomes included stress, anxiety and depression levels, measured using the Perceived Stress Scale (PSS), and the Hospital Anxiety Depression Scale (HADS) questionnaire, salivary cortisol levels and cognitive function measured using the Online General Cognitive Assessment Battery (CogniFit). All of these questionnaires were measured every 4 weeks. Blood and urine samples were collected to measure inflammatory markers, gut-brain-axis metabolites, short chain fatty acids (SCFA), and cranberry polyphenols metabolites. Faecal samples were also collected for measuring gut microbiome diversity and composition and faecal metabolomics. Diet was assessed using food frequency questionnaires (FFQ), 7-day food diaries (EPIC) and 24 h online dietary recalls (intake 24) during the study. Linear mixed-effect model (LMM) and ANCOVA were used to investigate the relationship between the 2 trial arms.

No significant differences were found between treatments for mood, stress levels, anxiety, depression, circulating short chain fatty acids or inflammatory markers, however a significantly lower diurnal area under the curve of salivary cortisol (p = 0.010) and significantly higher short-term memory (Z-score: p = 0.024; Raw-score: p = 0.034) was found at 12 weeks in the cranberry group compared with the placebo. Besides, significant differences between interventions were found in plasma gut-brain axis metabolites, including the kynurenine and bile acids pathway which were kynurenine (p = 0.023), kynurenic (p = 0.032), quinolinic (p = 0.018), and glycolithocholic acid (p = 0.04) as well as several plasma and urinary cranberry (poly)phenol metabolites were modulated by cranberry consumption.

In conclusion, daily cranberry (poly)phenol supplementation for 12 week did not improve mood, stress, anxiety, and depression symptoms in healthy university students, however it may modulate cortisol levels and some aspects of cognitive function via the gut-brain axis.

Previous studies in rodents suggest that mismatch between fetal and postnatal nutrition predisposes individuals to metabolic diseases. We hypothesized that in nonhuman primates (NHP), fetal programming of maternal undernutrition (MUN) persists postnatally with a dietary mismatch altering metabolic molecular systems that precede standard clinical measures. We used unbiased molecular approaches to examine response to a high fat, high-carbohydrate diet plus sugar drink (HFCS) challenge in NHP juvenile offspring of MUN pregnancies compared with controls (CON). Pregnant baboons were fed ad libitum (CON) or 30% calorie reduction from 0.16 gestation through lactation; weaned offspring were fed chow ad libitum. MUN offspring were growth restricted at birth. Liver, omental fat, and skeletal muscle gene expression, and liver glycogen, muscle mitochondria, and fat cell size were quantified. Before challenge, MUN offspring had lower body mass index (BMI) and liver glycogen, and consumed more sugar drink than CON. After HFCS challenge, MUN and CON BMIs were similar. Molecular analyses showed HFCS response differences between CON and MUN for muscle and liver, including hepatic splicing and unfolded protein response. Altered liver signaling pathways and glycogen content between MUN and CON at baseline indicate in utero programming persists in MUN juveniles. MUN catchup growth during consumption of HFCS suggests increased risk of obesity, diabetes, and cardiovascular disease. Greater sugar drink consumption in MUN demonstrates altered appetitive drive due to programming. Differences in blood leptin, liver glycogen, and tissue-specific molecular response to HFCS suggest MUN significantly impacts juvenile offspring ability to manage an energy rich diet.

Nitroaromatic compounds (NACs) are components of munitions commonly found as soil contaminants at military training sites and elsewhere. These compounds pose possible threats to human health and ecological systems. Recent studies indicate that these compounds are strongly retained by smectite clays. The adsorption mechanisms are not fully reconciled, but it is known that the type of exchangeable cation strongly affects NAC affinity for smectites. This study examined the sorption of 1,3-dinitrobenzene, 2,4-dinitrotoluene and naphthalene from water by a smectite clay (SWy-2) saturated with ammonium, tetramethylammonium (TMA), trimethylphenylammonium (TMPA) and hexadecyltrimethylammonium (HDTMA). In all cases, we observed greater sorption of 2,4-dinitrotoluene compared with 1,3-dinitrobenzene. The sorption isotherms for 2,4-dinitrotoluene and 1,3-dinitrobenzene displayed a concave-downward curve for NH4-SWy-2 and TMA-SWy-2, whereas the isotherms for sorption of HDTMA-SWy-2 and TMPA-SWy-2 were essentially linear. The magnitude of sorption followed the order: NH4-SWy-2 > TMA-SWy-2 > TMPA-SWy-2 > HDTMA-SWy-2 for both compounds. The greater affinity of NACs for NH4- and TMA-SWy-2 is due in part to complex formation between the exchangeable cation and −NO2 groups. These clays also provide near optimal interlayer distances that approximate the molecular thickness of NACs hence promoting the simultaneous interaction of the planar aromatic rings with opposing siloxane surfaces and solute dehydration. Both processes are energetically favorable. In HDTMA-SWy-2, sorption of all solutes is via a partition-dominated process. Solute competition (diminished uptake of one solute in the presence of a second) was observed for TMA-SWy-2 but not HDTMA-SWy-2. This is consistent with an adsorptive mechanism for TMA-SWy-2 and a partitioning mechanism for HDTMA-SWy-2. This study demonstrates that the dominant molecular mechanism of NAC sorption by smectite changes fundamentally from complexation between −NO2 groups and the exchangeable cation (viz. NH4 and TMA) to partitioning for a systematic series of ammonium and quaternary ammonium cations in which the locus of positive charge (the central N atom) is progressively shielded by organic moieties of increasing size.

Children with fragile X syndrome (FXS) often avoid eye contact, a behavior that is potentially related to hyperarousal. Prior studies, however, have focused on between-person associations rather than coupling of within-person changes in gaze behaviors and arousal. In addition, there is debate about whether prompts to maintain eye contact are beneficial for individuals with FXS. In a study of young females (ages 6–16), we used eye tracking to assess gaze behavior and pupil dilation during social interactions in a group with FXS (n = 32) and a developmentally similar comparison group (n = 23). Participants engaged in semi-structured conversations with a female examiner during blocks with and without verbal prompts to maintain eye contact. We identified a social–behavioral and psychophysiological profile that is specific to females with FXS; this group exhibited lower mean levels of eye contact, significantly increased mean pupil dilation during conversations that included prompts to maintain eye contact, and showed stronger positive coupling between eye contact and pupil dilation. Our findings strengthen support for the perspective that gaze aversion in FXS reflects negative reinforcement of social avoidance behavior. We also found that behavioral skills training may improve eye contact, but maintaining eye contact appears to be physiologically taxing for females with FXS.

This study aimed to assess human papillomavirus (HPV) vaccine effectiveness (VE) against both vaccine-type and nonvaccine-type high-risk HPV (hrHPV) infection, and duration of protection in United States. The study population was female participants aged 18–35 years with an HPV vaccination history and genital testing for HPV from the National Health and Nutrition Examination Survey, 2007–2016. Participants vaccinated before sexual debut were assessed against 13 nonvaccine-type hrHPV infection including 31/33/35/39/45/51/52/56/58/59/68/73/82. Multivariable logistic regression was used to estimate VE overall, by age at diagnosis, time since vaccination and lifetime sexual partners. A total of 3866 women were included in the analysis, with 23.3% (95% CI 21.3%–25.4%) having been vaccinated (≥1 dose). VE against vaccine-type HPV18/16/11/6 infection was 58% overall, which was mainly driven by those aged 18–22 years (VE = 64%) and 23–27 years (65%). Among participants aged 18–22 years vaccinated before sexual debut, the VE was 47% (23%–64%) against 13 nonvaccine-type hrHPV and 61% (95% CI 36%–77%) against 5 selected nonvaccine-type hrHPV35/39/52/58/59. Both direct effectiveness and cross-protection maintained effective for 5–10 years post vaccination. We also found the prevalence of ever diagnosed cervical cancer among vaccinated was significantly lower (0.46%, 4/874) than that among unvaccinated participants (1.27%, 38/2992). These findings highlight the potential of significant reduction of cervical cancer following the universal HPV vaccination programme.

Biogeochemical analyses of organisms’ tissues provide direct proxies for diets, behaviors, and environmental interactions that have proven invaluable for studies of extant and extinct species. Applying these to Cretaceous ecosystems has at times produced anomalous results, however, as dinosaurs preserve unusually positive stable carbon isotope compositions relative to extant C3-feeding vertebrates. This has been hypothesized to be a unique property of dinosaur dietary physiology, with potential significance for our interpretations of their paleobiology. We test that hypothesis through multi-taxic stable carbon isotope analyses of a spatiotemporally constrained locality in the Late Cretaceous of Canada, and compare the results to a modern near-analogue environment in Louisiana. The stable carbon isotope anomaly is present in all sampled fossil vertebrates, dinosaur or not. This suggests another more widespread factor is responsible. Examinations of diagenetic effects suggest that, where present, they are insufficient to explain the isotope anomaly. The isotope anomaly is therefore not primarily the result of a unique dietary physiology of dinosaurs, but rather a mix of factors impacting all taxa, such as environmental and/or source-diet differences. Our study underscores the importance of multi-taxic samples from spatiotemporally constrained localities in testing hypotheses of extinct organisms and ecosystems, and in the use of modern data to “ground truth” when evaluating analogue versus non-analogue conditions in greenhouse paleoecosystems.

The great demographic pressure brings tremendous volume of beef demand. The key to solve this problem is the growth and development of Chinese cattle. In order to find molecular markers conducive to the growth and development of Chinese cattle, sequencing was used to determine the position of copy number variations (CNVs), bioinformatics analysis was used to predict the function of ZNF146 gene, real-time fluorescent quantitative polymerase chain reaction (qPCR) was used for CNV genotyping and one-way analysis of variance was used for association analysis. The results showed that there exists CNV in Chr 18: 47225201-47229600 (5.0.1 version) of ZNF146 gene through the early sequencing results in the laboratory and predicted ZNF146 gene was expressed in liver, skeletal muscle and breast cells, and was amplified or overexpressed in pancreatic cancer, which promoted the development of tumour through bioinformatics. Therefore, it is predicted that ZNF146 gene affects the proliferation of muscle cells, and then affects the growth and development of cattle. Furthermore, CNV genotyping of ZNF146 gene was three types (deletion type, normal type and duplication type) by Real-time fluorescent quantitative PCR (qPCR). The association analysis results showed that ZNF146-CNV was significantly correlated with rump length of Qinchuan cattle, hucklebone width of Jiaxian red cattle and heart girth of Yunling cattle. From the above results, ZNF146-CNV had a significant effect on growth traits, which provided an important candidate molecular marker for growth and development of Chinese cattle.

In this prospective, longitudinal study, we examined the risk factors for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection among a cohort of chronic hemodialysis (HD) patients and healthcare personnel (HCPs) over a 6-month period. The risk of SARS-CoV-2 infection among HD patients and HCPs was consistently associated with a household member having SARS-CoV-2 infection.

The Hierarchical Taxonomy of Psychopathology (HiTOP) has emerged out of the quantitative approach to psychiatric nosology. This approach identifies psychopathology constructs based on patterns of co-variation among signs and symptoms. The initial HiTOP model, which was published in 2017, is based on a large literature that spans decades of research. HiTOP is a living model that undergoes revision as new data become available. Here we discuss advantages and practical considerations of using this system in psychiatric practice and research. We especially highlight limitations of HiTOP and ongoing efforts to address them. We describe differences and similarities between HiTOP and existing diagnostic systems. Next, we review the types of evidence that informed development of HiTOP, including populations in which it has been studied and data on its validity. The paper also describes how HiTOP can facilitate research on genetic and environmental causes of psychopathology as well as the search for neurobiologic mechanisms and novel treatments. Furthermore, we consider implications for public health programs and prevention of mental disorders. We also review data on clinical utility and illustrate clinical application of HiTOP. Importantly, the model is based on measures and practices that are already used widely in clinical settings. HiTOP offers a way to organize and formalize these techniques. This model already can contribute to progress in psychiatry and complement traditional nosologies. Moreover, HiTOP seeks to facilitate research on linkages between phenotypes and biological processes, which may enable construction of a system that encompasses both biomarkers and precise clinical description.

The incidence of scarlet fever has increased dramatically in recent years in Chongqing, China, but there has no effective method to forecast it. This study aimed to develop a forecasting model of the incidence of scarlet fever using a seasonal autoregressive integrated moving average (SARIMA) model. Monthly scarlet fever data between 2011 and 2019 in Chongqing, China were retrieved from the Notifiable Infectious Disease Surveillance System. From 2011 to 2019, a total of 5073 scarlet fever cases were reported in Chongqing, the male-to-female ratio was 1.44:1, children aged 3–9 years old accounted for 81.86% of the cases, while 42.70 and 42.58% of the reported cases were students and kindergarten children, respectively. The data from 2011 to 2018 were used to fit a SARIMA model and data in 2019 were used to validate the model. The normalised Bayesian information criterion (BIC), the coefficient of determination (R2) and the root mean squared error (RMSE) were used to evaluate the goodness-of-fit of the fitted model. The optimal SARIMA model was identified as (3, 1, 3) (3, 1, 0)12. The RMSE and mean absolute per cent error (MAPE) were used to assess the accuracy of the model. The RMSE and MAPE of the predicted values were 19.40 and 0.25 respectively, indicating that the predicted values matched the observed values reasonably well. Taken together, the SARIMA model could be employed to forecast scarlet fever incidence trend, providing support for scarlet fever control and prevention.