Paediatric obesity and Crohn's disease: a descriptive review of disease phenotype and clinical course.

Objectives: In an era of increasing paediatric obesity and inflammatory bowel disease (IBD), this study evaluates the disease phenotype and clinical course of Crohn's disease (CD) in paediatric patients who are obese or overweight. Methods: This is a retrospective, single-center, descriptive observational study from January 2010 to May 2020. Participants were included if they were: aged 2 to 18 years at the time of diagnosis, had a confirmed diagnosis of CD, and met WHO criteria for overweight or obesity at the time of diagnosis or within one year before diagnosis. Results: A total of 345 patient charts with CD were screened during the study period, with 16 patients meeting inclusion criteria. Median age of patients was 15.5 years (IQR = 13.6, 16.1). Of the 15 patients over 10 years of age, median anthropometrics at diagnosis included body mass index (BMI) of 27.2 (IQR = 24.9, 29.4) and BMI for age z-score of 1.82 (IQR = 1.58, 2.19). Presenting symptoms included abdominal pain (80.0%), diarrhea (66.7%), hematochezia (66.7%), and weight loss (26.7%). Five patients (33.3%) had obesity-related complications. Median time from symptom onset to diagnosis was 146 days (IQR = 31, 367), and median time from diagnosis to remission was 229 days (IQR = 101.8, 496.3). Conclusions: Patients with elevated BMI and CD present with typical symptoms of IBD, although weight loss was a less common presenting symptom. Time to disease remission is delayed, and obesity-related complications are common. Primary care providers must have a high degree of clinical suspicion in patients to prevent delays to gastroenterology referral and to improve time to disease remission.

Fully Human Bifunctional Intrabodies Achieve Graded Reduction of Intracellular Tau and Rescue Survival of MAPT Mutation iPSC-derived Neurons.

Tau protein aggregation is a hallmark of several neurodegenerative diseases, including Alzheimer's disease, frontotemporal dementia (FTD) and progressive supranuclear palsy (PSP), spurring development of tau-lowering therapeutic strategies. Here, we report fully human bifunctional anti-tau-PEST intrabodies that bind the mid-domain of tau to block aggregation and degrade tau via the proteasome using the ornithine decarboxylase (ODC) PEST degron. They effectively reduced tau protein in human iPSC-derived cortical neurons in 2D cultures and 3D organoids, including those with the disease-associated tau mutations R5L, N279K, R406W, and V337M. Anti-tau-hPEST intrabodies facilitated efficient ubiquitin-independent proteolysis, in contrast to tau-lowering approaches that rely on the cell's ubiquitination system. Importantly, they counteracted the proteasome impairment observed in V337M patient-derived cortical neurons and significantly improved neuronal survival. By serial mutagenesis, we created variants of the PEST degron that achieved graded levels of tau reduction. Moderate reduction was as effective as high reduction against tau V337M-induced neural cell death.

Correction: Risk of Suicide and Self-Harm Following Gender-Affirmation Surgery.

[This corrects the article DOI: 10.7759/cureus.57472.].

Poppers maculopathy missed in a patient with cataract highlights the importance of preoperative optical coherence tomography.

Poppers maculopathy is a complication of alkyl nitrate (poppers) inhalation. It presents with non-specific symptoms and variable signs, which can make it difficult to diagnose. We present a case of coexisting cataract and poppers maculopathy in a patient. He had vague visual symptoms that were attributed entirely to his cataract and he went on to have cataract surgery. Suboptimal postoperative visual acuity and normal clinical examination triggered further investigation with spectral-domain optical coherence tomography (SD-OCT), after which poppers maculopathy was diagnosed. We highlight the importance of performing OCT in the preoperative assessment of a cataract patient, especially where the cataract is mild and may not fully account for symptoms. The patient showed complete visual recovery on drug cessation despite ongoing maculopathy on OCT scans.

Microbial aromatic amino acid metabolism is modifiable in fermented food matrices to promote bioactivity.

Ingestion of fermented foods impacts human immune function, yet the bioactive food components underlying these effects are not understood. Here, we interrogated whether fermented food bioactivity relates to microbial metabolites derived from aromatic amino acids, termed aryl-lactates. Using targeted metabolomics, we established the presence of aryl-lactates in commercially available fermented foods. After pinpointing fermented food-associated lactic acid bacteria that produce high levels of aryl-lactates, we identified fermentation conditions to increase aryl-lactate production in food matrices up to 5 × 103 fold vs. standard fermentation conditions. Using ex vivo reporter assays, we found that food matrix conditions optimized for aryl-lactate production exhibited enhanced agonist activity for the human aryl-hydrocarbon receptor (AhR) as compared to standard fermentation conditions and commercial products. Reduced microbial-induced AhR activity has emerged as a hallmark of many chronic inflammatory diseases, thus we envision strategies to enhance AhR bioactivity of fermented foods to be leveraged to improve human health.

Spatial Single-cell Analysis Decodes Cortical Layer and Area Specification.

The human cerebral cortex, pivotal for advanced cognitive functions, is composed of six distinct layers and dozens of functionally specialized areas 1,2 . The layers and areas are distinguished both molecularly, by diverse neuronal and glial cell subtypes, and structurally, through intricate spatial organization 3,4 . While single-cell transcriptomics studies have advanced molecular characterization of human cortical development, a critical gap exists due to the loss of spatial context during cell dissociation 5,6,7,8 . Here, we utilized multiplexed error-robust fluorescence in situ hybridization (MERFISH) 9 , augmented with deep-learning-based cell segmentation, to examine the molecular, cellular, and cytoarchitectural development of human fetal cortex with spatially resolved single-cell resolution. Our extensive spatial atlas, encompassing 16 million single cells, spans eight cortical areas across four time points in the second and third trimesters. We uncovered an early establishment of the six-layer structure, identifiable in the laminar distribution of excitatory neuronal subtypes by mid-gestation, long before the emergence of cytoarchitectural layers. Notably, while anterior-posterior gradients of neuronal subtypes were generally observed in most cortical areas, a striking exception was the sharp molecular border between primary (V1) and secondary visual cortices (V2) at gestational week 20. Here we discovered an abrupt binary shift in neuronal subtype specification at the earliest stages, challenging the notion that continuous morphogen gradients dictate mid-gestation cortical arealization 6,10 . Moreover, integrating single-nuclei RNA-sequencing and in situ whole transcriptomics revealed an early upregulation of synaptogenesis in V1-specific Layer 4 neurons, suggesting a role of synaptogenesis in this discrete border formation. Collectively, our findings underscore the crucial role of spatial relationships in determining the molecular specification of cortical layers and areas. This work not only provides a valuable resource for the field, but also establishes a spatially resolved single-cell analysis paradigm that paves the way for a comprehensive developmental atlas of the human brain.

Longitudinal analysis of clinical and laboratory biomarkers in a patient with familial lecithin: Cholesterol acyltransferase deficiency (FLD) and accelerated eGFR decline: A case study.

Familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) is an ultra-rare autosomal recessive disease characterized by very low HDL-C levels, corneal opacity, anemia, and progressive renal disease. The rate and severity of renal disease are variable across FLD patients and the biomarkers and risk factors for disease progression are poorly understood. Here we report a 30 year-long comparative analysis of the clinical and laboratory biomarkers in an FLD patient with accelerated renal decline, who underwent 2 kidney and one liver transplantations. Results show that elevated TG and non-HDL-C levels may promote the formation of LpX and accelerate renal function decline, whereas markers of anemia may be early predictors. Conversely, corneal opacity progresses at a steady rate and does not correlate with lipid, hematologic, or renal biomarkers. Our study suggests that monitoring of markers of anemia may aid the early detection and timely management of kidney disease with conservative therapies. Furthermore, it suggests that controlling hypercholesterolemia and hypertriglyceridemia may help improve renal disease prognosis.

Enhanced liver fibrosis (ELF) score predicts hepatic decompensation and mortality.

Background & Aims: In community pathways for detection of liver disease the most common reason for referral is fibrosis assessment. We investigated the impact of adding the Enhanced Liver Fibrosis (ELF) score as a second-line test (subsequent to an indeterminate or high Fibrosis-4 index [FIB-4] and/or non-alcoholic fatty liver disease fibrosis score) to guide referral and prognostication in our multi-aetiology pathway. Methods: Patients with ELF results from the intelligent Liver Function Testing (iLFT) pathway were recruited. Case note review was undertaken to compare ELF with endpoints of cirrhosis, hepatic decompensation, and mortality (liver-related and all-cause death). Results: In total, 1,327 individuals were included with a median follow-up of 859 days and median ELF score of 10.2. Overall sensitivity for cirrhosis at the 9.8 threshold was 94% (100% for metabolic-associated steatotic liver disease, 89% for alcohol-related liver disease). Determination of the ELF score as a second-line test reduced the referral rate by 34%. ELF scores predicted hepatic outcomes; each unit change was associated with increased decompensation (adjusted Hazard Ratio [aHR] 2.215, 95% CI: 1.934-2.537) and liver-related mortality (aHR 2.024, 95% CI: 1.674-2.446). ELF outperformed FIB-4 for risk of liver-related mortality, particularly in the short-term (area under the curve [AUC] 94.3% vs. 82.8% at six months). Where FIB-4 was indeterminate, ELF had higher AUC for all outcomes within at least 2 years. ELF ≥13 was associated with particularly high rates of decompensation (26% within 90 days) and all-cause mortality (38% at 1 year). Conclusions: The addition of ELF reduced the number of individuals referred for fibrosis assessment following iLFT pathway testing and provided useful prognostic information. Individuals with ELF scores ≥13 were considered at high-risk of negative outcomes warranting urgent clinical assessment. Impact and implications: Primary care pathways for suspected liver disease are increasingly common and often lead to increased specialist hepatology referrals for fibrosis assessment. This study, using clinical follow-up for liver-related outcomes, provides further evidence supporting ELF testing to safely reduce referrals in a two-step approach when combined with other simple fibrosis markers. Additionally, ELF scores predict liver-related morbidity and mortality, with ELF scores ≥13 indicating particularly high-risk patients. This study may help inform the implementation of diagnostic pathways for early detection of liver disease and highlights the need for urgent review of individuals with very high ELF scores.

Honey Added to Yogurt with Bifidobacterium animalis subsp. lactis DN-173 010/CNCM I-2494 Supports Probiotic Enrichment but Does Not Reduce Intestinal Transit Time in Healthy Adults: A Randomized, Controlled, Crossover Trial.

BACKGROUND: Honey improves probiotic survival in vitro. However, if this effect translates to humans has not been investigated. OBJECTIVES: We aimed to determine effects of honey plus yogurt containing the probiotic Bifidobacterium animalis subsp. lactis DN-173 010/CNCM I-2494 (B. animalis) on intestinal transit time, probiotic enrichment, digestive health, mood, and cognition in adults. METHODS: Sixty-six healthy adults (34 female; 33.6 ± 9.8 y; 24.6 ± 3.0 kg/m2) in a crossover trial were randomly assigned to 2-wk yogurt conditions in a counterbalanced order with ≥4-wk washout: 1) Honey (HON): yogurt plus honey and 2) Negative Control (NC): heat-treated yogurt plus sugar. Of the participants, n = 62 completed the trial, and n = 37 (17 female; 32.0 ± 8.3 y; 25.0 ± 2.9 kg/m2) elected to enroll in a third condition (a nonrandomized study extension) after ≥4-wk washout with a reference Positive Control (PC): yogurt plus sugar. At baseline and end of each of the 3 conditions, intestinal transit time was measured with dye capsules; probiotic abundance with fecal sample 16S sequencing; digestive health with symptom/function records, Bristol stool consistency, Gastrointestinal Tolerability, and Gastrointestinal Quality of Life Index; mood with Positive and Negative Affect Schedule-Short Form, Depression Anxiety Stress Scales-42, Patient-Reported Outcomes Measurement Information System questionnaires, and an emotional image task; and cognition with a spatial reconstruction task. Data were analyzed using linear mixed-effects models (LMMs) with significance at P ≤ 0.05. Baseline and end data were included in the LMM, with fixed effects being treatment, time, treatment by time interaction, and baseline covariate, and the random effect being the participant. RESULTS: B. animalis was enriched in HON (d = 3.54; P = 0.0002) compared to controls with linear discriminant analysis effect size. Intestinal transit time, gastrointestinal health, mood, and cognition did not differ between conditions (LMM: Ps > 0.05). CONCLUSIONS: Yogurt + honey enriched B. animalis but did not reduce intestinal transit time or have other functional gastrointestinal, mood, or cognitive effects in adults. This trial was registered at www. CLINICALTRIALS: gov as NCT04187950 and NCT04901390.

A Critical Review of Mindfulness Measures.

Background and Purpose: Mindfulness has been associated with many positive psychological benefits. It is usually measured by self-report, and there are numerous questionnaires available to measure mindfulness in this way. The purpose of this review is to offer a summary of the available self-assessment questionnaires for measuring mindfulness, their appropriate uses, and psychometrics. Methods: CINAHL, PubMed, and PsychINFO databases were queried along with hand searching reference lists based on the indicated criteria, including Mindfulness-Based Stress Reduction-related mindfulness measurement tools, based on self-report and designed for use in adults. Results: Fourteen tools, published between 2001 and 2021, were included in this review. The tools varied in their orientation and have been created to measure mindfulness as a state, trait, and process. Conclusions: There is a wide variety of available tools, and each conceptualizes mindfulness in a distinct way. Understanding these details is crucial to choosing the proper tool.

Implanted Pulse Generators in Lower Extremity Neuroprostheses: A 25-Year Review.

OBJECTIVES: Neuroprosthetic devices can improve quality of life by providing an alternative option for motor function lost after spinal cord injury, stroke, and other central nervous system disorders. The objective of this study is to analyze the outcomes of implanted pulse generators that our research group installed in volunteers with paralysis to assist with lower extremity function over a 25-year period, specifically, to determine survival rates and common modes of malfunction, reasons for removal or revision, and precipitating factors or external events that may have adversely influenced device performance. MATERIALS AND METHODS: Our implantable receiver-stimulator (IRS-8) and implantable stimulator-telemeter (IST-12 and IST-16) device histories were retrospectively reviewed through surgical notes, regulatory documentation, and manufacturing records from 1996 to 2021. RESULTS: Most of the 65 devices (64.6%) implanted in 43 volunteers remain implanted and operational. Seven underwent explantation owing to infection; seven had internal failures, and six were physically broken by external events. Of the 22 devices explanted, 15 were successfully replaced to restore recipients' enhanced functionality. There were no instances of sepsis or major health complications. The five infections that followed all 93 IRS and IST lower extremity research surgeries during this period indicate a pooled infection rate of 5.4%. The Kaplan-Meier analysis of technical malfunctions between the implant date and most recent follow-up shows five-, ten-, and 20-year device survival rates of 92%, 84%, and 71%, respectively. CONCLUSIONS: Incidence of malfunction is similar to, whereas infection rates are slightly higher than, other commonly implanted medical devices. Future investigations will focus on infection prevention, modifying techniques on the basis of recipient demographics, lifestyle factors, and education, and integrating similar experience of motor neuroprostheses used in other applications.

Amyloid-ß Deposition Predicts Grocery Shopping Performance in Older Adults Without Cognitive Impairment.

Background: A screening tool sensitive to Alzheimer's disease (AD) risk factors, such as amyloid-ß (Aß) deposition, and subtle cognitive changes, best elicited by complex everyday tasks, is needed. Objective: To determine if grocery shopping performance could differentiate older adults at elevated risk of developing AD (OAer), older adults at low risk of developing AD (OAlr), and young adults (YA), and if amount of Aß deposition could predict grocery shopping performance in older adults (OA). Methods: Twenty-one OAer (78±5 years), 33 OAlr (78±5 years), and 28 YA (31±3 years) performed four grocery shopping trials, with the best and worst performances analyzed. Measures included trial time, number of correct items, number of grocery note fixations, and number of fixations and percentage of time fixating on the correct shelving unit, correct brand, and correct shelf. Linear mixed effects models compared measures by performance rank (best, worst) and group (OAer, OAlr, YA), and estimated the effect of Aß deposition on measures in OA. Results: Relative to their best performance, OAer and OAlr exhibited more correct shelving unit fixations and correct brand fixations during their worst performance, while YA did not. Within OA's worst performance, greater Aß deposition was associated with a smaller percentage of time fixating on the correct shelving unit, correct shelf, and correct brand. Within OA, greater Aß deposition was associated with more grocery note fixations. Conclusions: OA with elevated Aß deposition may exhibit subtle working memory impairments and less efficient visual search strategies while performing a cognitively demanding everyday task.

Oesophageal cell collection device and biomarker testing to identify high-risk Barrett's patients requiring endoscopic investigation.

BACKGROUND: Barrett's oesophagus surveillance places significant burden on endoscopy services yet is vital to detect early cancerous change. Oesophageal cell collection device (OCCD) testing was introduced across Scotland for Barrett's surveillance in response to the COVID-19 pandemic. This national pragmatic retrospective study presents the CytoSCOT programme results and evaluates whether OCCD testing is successfully identifying high-risk Barrett's patients requiring urgent endoscopy. METHODS: All patients undergoing OCCD testing for Barrett's surveillance across 11 Scottish health boards over a 32-month period were identified. Patients who underwent endoscopy within 12 months of OCCD test were included. Individual patient records were interrogated to record clinical information and OCCD test result to categorize patients into risk groups. Endoscopic histopathology results were analysed according to risk group and segment length. Patients were deemed high risk if the OCCD test demonstrated atypia and/or p53 positivity. RESULTS: 4204 OCCD tests were performed in 3745 patients: 608 patients underwent endoscopy within 12 months and were included in this analysis. Patients with longer Barrett's segments were significantly more likely to have an abnormal OCCD test. 50/608 patients (8.2%) had high-grade dysplasia or cancer on endoscopic biopsies: this equates to 1.3% of the total group (50/3745). 46/50 patients (92.0%) were deemed high risk, triggering urgent endoscopy: this rose to 100% with insufficient tests removed. There were no cancers diagnosed within 12 months post-OCCD in the low-risk group. CONCLUSION: OCCD testing is an effective triage tool to identify high-risk patients with Barrett's oesophagus requiring further investigation with endoscopy within the real-world setting.

Giant electron-mediated phononic nonlinearity in semiconductor-piezoelectric heterostructures.

Efficient and deterministic nonlinear phononic interactions could revolutionize classical and quantum information processing at radio frequencies in much the same way that nonlinear photonic interactions have at optical frequencies. Here we show that in the important class of phononic materials that are piezoelectric, deterministic nonlinear phononic interactions can be enhanced by orders of magnitude via the heterogeneous integration of high-mobility semiconductor materials. To this end, a lithium niobate and indium gallium arsenide heterostructure is utilized to produce the most efficient three- and four-wave phononic mixing to date, to the best of our knowledge. We then show that the conversion efficiency can be further enhanced by applying semiconductor bias fields that amplify the phonons. We present a theoretical model that accurately predicts the three-wave mixing efficiencies in this work and extrapolate that these nonlinearities can be enhanced far beyond what is demonstrated here by confining phonons to smaller dimensions in waveguides and optimizing the semiconductor material properties.

Risk of Suicide and Self-Harm Following Gender-Affirmation Surgery.

Introduction With the growing acceptance of transgender individuals, the number of gender affirmation surgeries has increased. Transgender individuals face elevated depression rates, leading to an increase in suicide ideation and attempts. This study evaluates the risk of suicide or self-harm associated with gender affirmation procedures. Methods This retrospective study utilized de-identified patient data from the TriNetX (TriNetX, LLC, Cambridge, MA) database, involving 56 United States healthcare organizations and over 90 million patients. The study involved four cohorts: cohort A, adults aged 18-60 who had gender-affirming surgery and an emergency visit (N = 1,501); cohort B, control group of adults with emergency visits but no gender-affirming surgery (N = 15,608,363); and cohort C, control group of adults with emergency visits, tubal ligation or vasectomy, but no gender-affirming surgery (N = 142,093). Propensity matching was applied to cohorts A and C. Data from February 4, 2003, to February 4, 2023, were analyzed to examine suicide attempts, death, self-harm, and post-traumatic stress disorder (PTSD) within five years of the index event. A secondary analysis involving a control group with pharyngitis, referred to as cohort D, was conducted to validate the results from cohort C. Results Individuals who underwent gender-affirming surgery had a 12.12-fold higher suicide attempt risk than those who did not (3.47% vs. 0.29%, RR 95% CI 9.20-15.96, p < 0.0001). Compared to the tubal ligation/vasectomy controls, the risk was 5.03-fold higher before propensity matching and remained significant at 4.71-fold after matching (3.50% vs. 0.74%, RR 95% CI 2.46-9.024, p < 0.0001) for the gender affirmation patients with similar results with the pharyngitis controls. Conclusion Gender-affirming surgery is significantly associated with elevated suicide attempt risks, underlining the necessity for comprehensive post-procedure psychiatric support.

Life at the interface: Engineering bio-nanomaterials through interfacial molecular self-assembly.

Interfacial self-assembly describes the directed organization of molecules and colloids at phase boundaries. Believed to be fundamental to the inception of primordial life, interfacial assembly is exploited by a myriad of eukaryotic and prokaryotic organisms to execute physiologic activities and maintain homeostasis. Inspired by these natural systems, chemists, engineers, and materials scientists have sought to harness the thermodynamic equilibria at phase boundaries to create multi-dimensional, highly ordered, and functional nanomaterials. Recent advances in our understanding of the biophysical principles guiding molecular assembly at gas-solid, gas-liquid, solid-liquid, and liquid-liquid interphases have enhanced the rational design of functional bio-nanomaterials, particularly in the fields of biosensing, bioimaging and biotherapy. Continued development of non-canonical building blocks, paired with deeper mechanistic insights into interphase self-assembly, holds promise to yield next generation interfacial bio-nanomaterials with unique, and perhaps yet unrealized, properties. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Lead Optimization of Small Molecule ENL YEATS Inhibitors to Enable In Vivo Studies: Discovery of TDI-11055.

Eleven-nineteen leukemia (ENL) is an epigenetic reader protein that drives oncogenic transcriptional programs in acute myeloid leukemia (AML). AML is one of the deadliest hematopoietic malignancies, with an overall 5-year survival rate of 27%. The epigenetic reader activity of ENL is mediated by its YEATS domain that binds to acetyl and crotonyl marks on histone tails and colocalizes with promoters of actively transcribed genes that are essential for leukemia. Prior to the discovery of TDI-11055, existing inhibitors of ENL YEATS showed in vitro potency, but had not shown efficacy in in vivo animal models. During the course of the medicinal chemistry campaign described here, we identified ENL YEATS inhibitor TDI-11055 that has an improved pharmacokinetic profile and is appropriate for in vivo evaluation of the ENL YEATS inhibition mechanism in AML.

Effectiveness of BNT162b2 COVID-19 primary series vaccination in children aged 5-17 years in the United States: a cohort study.

BACKGROUND: COVID-19 vaccines are authorized for use in children in the United States; real-world assessment of vaccine effectiveness in children is needed. This study's objective was to estimate the effectiveness of receiving a complete primary series of monovalent BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine in US children. METHODS: This cohort study identified children aged 5-17 years vaccinated with BNT162b2 matched with unvaccinated children. Participants and BNT162b2 vaccinations were identified in Optum and CVS Health insurance administrative claims databases linked with Immunization Information System (IIS) COVID-19 vaccination records from 16 US jurisdictions between December 11, 2020, and May 31, 2022 (end date varied by database and IIS). Vaccinated children were followed from their first BNT162b2 dose and matched to unvaccinated children on calendar date, US county of residence, and demographic and clinical factors. Censoring occurred if vaccinated children failed to receive a timely dose 2 or if unvaccinated children received any dose. Two COVID-19 outcome definitions were evaluated: COVID-19 diagnosis in any medical setting and COVID-19 diagnosis in hospitals/emergency departments (EDs). Propensity score-weighted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with Cox proportional hazards models, and vaccine effectiveness (VE) was estimated as 1 minus HR. VE was estimated overall, within age subgroups, and within variant-specific eras. Sensitivity, negative control, and quantitative bias analyses evaluated various potential biases. RESULTS: There were 453,655 eligible vaccinated children one-to-one matched to unvaccinated comparators (mean age 12 years; 50% female). COVID-19 hospitalizations/ED visits were rare in children, regardless of vaccination status (Optum, 41.2 per 10,000 person-years; CVS Health, 44.1 per 10,000 person-years). Overall, vaccination was associated with reduced incidence of any medically diagnosed COVID-19 (meta-analyzed VE = 38% [95% CI, 36-40%]) and hospital/ED-diagnosed COVID-19 (meta-analyzed VE = 61% [95% CI, 56-65%]). VE estimates were lowest among children 5-11 years and during the Omicron-variant era. CONCLUSIONS: Receipt of a complete BNT162b2 vaccine primary series was associated with overall reduced medically diagnosed COVID-19 and hospital/ED-diagnosed COVID-19 in children; observed VE estimates differed by age group and variant era. REGISTRATION: The study protocol was publicly posted on the BEST Initiative website ( https://bestinitiative.org/wp-content/uploads/2022/03/C19-VX-Effectiveness-Protocol_2022_508.pdf ).

Cross-modality mapping using image varifolds to align tissue-scale atlases to molecular-scale measures with application to 2D brain sections.

This paper explicates a solution to building correspondences between molecular-scale transcriptomics and tissue-scale atlases. This problem arises in atlas construction and cross-specimen/technology alignment where specimens per emerging technology remain sparse and conventional image representations cannot efficiently model the high dimensions from subcellular detection of thousands of genes. We address these challenges by representing spatial transcriptomics data as generalized functions encoding position and high-dimensional feature (gene, cell type) identity. We map onto low-dimensional atlas ontologies by modeling regions as homogeneous random fields with unknown transcriptomic feature distribution. We solve simultaneously for the minimizing geodesic diffeomorphism of coordinates through LDDMM and for these latent feature densities. We map tissue-scale mouse brain atlases to gene-based and cell-based transcriptomics data from MERFISH and BARseq technologies and to histopathology and cross-species atlases to illustrate integration of diverse molecular and cellular datasets into a single coordinate system as a means of comparison and further atlas construction.

Effects of 2'-fucosyllactose on the viability of starter cultures and Bifidobacterium strains of human origin in yogurt during refrigerated storage.

2'-Fucosyllactose (2'-FL) is postulated to provide health benefits and promote the growth of probiotics. This work was undertaken to study the effects of 2'-FL on the viability of starter cultures and Bifidobacterium strains of human origin in yogurt during refrigerated storage. Yogurts were produced containing 2'-FL (0 or 2 g/L) and Bifidobacterium strains of human origin (Bifidobacterium longum subsp. longum BB536 or Bifidobacterium longum subsp. infantis ATCC 15697) at a concentration of at least 109 CFU/mL. All yogurts were stored at 4°C for 5 weeks. Results showed that 2'-FL was stable in yogurts for at least 5 weeks of cold storage, and the addition of 2'-FL did not significantly alter yogurt fermentation parameters, associated metabolites, and the viability of mixed yogurt starter cultures and Bifidobacterium strains (p > 0.05). The addition of bifidobacteria had a negative impact (p < 0.05) on the survival rate of starter cultures, Streptococcus thermophilus and Lactobacillus delbureckii subsp. bulgaricus. Meanwhile, it is difficult to maintain a high survival rate of bifidobacteria in final yogurt products, and the addition of 2'-FL could not enhance the viability of bifidobacteria. B. longum BB536 survived at a level higher than 106 CFU/g for 28 days, while B. infantis ATCC15697 maintained this level for only 7 days. In summary, this study has shown the impact of 2'-FL and bifidobacterial species on yogurt properties, and results suggest that it is promising to use 2'-FL in yogurt products as a prebiotic. PRACTICAL APPLICATION: Yogurt is known for its beneficial effects on human health and nutrition. This study reported the production of symbiotic yogurt containing bifidobacteria and 2'-fucosyllactose (2'-FL) as a functional food for specified health uses. The viability of yogurt starter cultures and probiotic bifidobacterial strains was analyzed in this study. Moreover, this research demonstrated that 2'-FL could be added to yogurt without affecting the characteristics of yogurt significantly.