Conditionally mutant animal model for investigating the invasive trophoblast cell lineage.

Placental development involves coordinated expansion and differentiation of trophoblast cell lineages possessing specialized functions. Among the differentiated trophoblast cell lineages are invasive trophoblast cells, which exit the placenta and invade the uterus, where they restructure the uterine parenchyma and facilitate remodeling of uterine spiral arteries. The rat exhibits deep intrauterine trophoblast cell invasion, a feature shared with human placentation, and is also amenable to gene manipulation using genome-editing techniques. In this investigation, we generated a conditional rat model targeting the invasive trophoblast cell lineage. Prolactin family 7, subfamily b, member 1 (Prl7b1) is uniquely and abundantly expressed in the rat invasive trophoblast cell lineage. Disruption of Prl7b1 did not adversely affect placental development. We demonstrated that the Prl7b1 locus could be effectively used to drive the expression of Cre recombinase in invasive trophoblast cells. Our rat model represents a new tool for investigating candidate genes contributing to the regulation of invasive trophoblast cells and their roles in trophoblast-guided uterine spiral artery remodeling.

Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer.

BACKGROUND: Neoadjuvant or adjuvant immunotherapy can improve outcomes in patients with resectable non-small-cell lung cancer (NSCLC). Perioperative regimens may combine benefits of both to improve long-term outcomes. METHODS: We randomly assigned patients with resectable NSCLC (stage II to IIIB [N2 node stage] according to the eighth edition of the AJCC Cancer Staging Manual) to receive platinum-based chemotherapy plus durvalumab or placebo administered intravenously every 3 weeks for 4 cycles before surgery, followed by adjuvant durvalumab or placebo intravenously every 4 weeks for 12 cycles. Randomization was stratified according to disease stage (II or III) and programmed death ligand 1 (PD-L1) expression (≥1% or <1%). Primary end points were event-free survival (defined as the time to the earliest occurrence of progressive disease that precluded surgery or prevented completion of surgery, disease recurrence [assessed in a blinded fashion by independent central review], or death from any cause) and pathological complete response (evaluated centrally). RESULTS: A total of 802 patients were randomly assigned to receive durvalumab (400 patients) or placebo (402 patients). The duration of event-free survival was significantly longer with durvalumab than with placebo; the stratified hazard ratio for disease progression, recurrence, or death was 0.68 (95% confidence interval [CI], 0.53 to 0.88; P = 0.004) at the first interim analysis. At the 12-month landmark analysis, event-free survival was observed in 73.4% of the patients who received durvalumab (95% CI, 67.9 to 78.1), as compared with 64.5% of the patients who received placebo (95% CI, 58.8 to 69.6). The incidence of pathological complete response was significantly greater with durvalumab than with placebo (17.2% vs. 4.3% at the final analysis; difference, 13.0 percentage points; 95% CI, 8.7 to 17.6; P<0.001 at interim analysis of data from 402 patients). Event-free survival and pathological complete response benefit were observed regardless of stage and PD-L1 expression. Adverse events of maximum grade 3 or 4 occurred in 42.4% of patients with durvalumab and in 43.2% with placebo. Data from 62 patients with documented EGFR or ALK alterations were excluded from the efficacy analyses in the modified intention-to-treat population. CONCLUSIONS: In patients with resectable NSCLC, perioperative durvalumab plus neoadjuvant chemotherapy was associated with significantly greater event-free survival and pathological complete response than neoadjuvant chemotherapy alone, with a safety profile that was consistent with the individual agents. (Funded by AstraZeneca; AEGEAN ClinicalTrials.gov number, NCT03800134.).

Unsupervised contrastive peak caller for ATAC-seq.

The assay for transposase-accessible chromatin with sequencing (ATAC-seq) is a common assay to identify chromatin accessible regions by using a Tn5 transposase that can access, cut, and ligate adapters to DNA fragments for subsequent amplification and sequencing. These sequenced regions are quantified and tested for enrichment in a process referred to as "peak calling." Most unsupervised peak calling methods are based on simple statistical models and suffer from elevated false positive rates. Newly developed supervised deep learning methods can be successful, but they rely on high quality labeled data for training, which can be difficult to obtain. Moreover, though biological replicates are recognized to be important, there are no established approaches for using replicates in the deep learning tools, and the approaches available for traditional methods either cannot be applied to ATAC-seq, where control samples may be unavailable, or are post hoc and do not capitalize on potentially complex, but reproducible signal in the read enrichment data. Here, we propose a novel peak caller that uses unsupervised contrastive learning to extract shared signals from multiple replicates. Raw coverage data are encoded to obtain low-dimensional embeddings and optimized to minimize a contrastive loss over biological replicates. These embeddings are passed to another contrastive loss for learning and predicting peaks and decoded to denoised data under an autoencoder loss. We compared our replicative contrastive learner (RCL) method with other existing methods on ATAC-seq data, using annotations from ChromHMM genomic labels and transcription factor ChIP-seq as noisy truth. RCL consistently achieved the best performance.

Core conserved transcriptional regulatory networks define the invasive trophoblast cell lineage.

The invasive trophoblast cell lineages in rat and human share crucial responsibilities in establishing the uterine-placental interface of the hemochorial placenta. These observations have led to the rat becoming an especially useful animal model for studying hemochorial placentation. However, our understanding of similarities or differences between regulatory mechanisms governing rat and human invasive trophoblast cell populations is limited. In this study, we generated single-nucleus ATAC-seq data from gestation day 15.5 and 19.5 rat uterine-placental interface tissues, and integrated the data with single-cell RNA-seq data generated at the same stages. We determined the chromatin accessibility profiles of invasive trophoblast, natural killer, macrophage, endothelial and smooth muscle cells, and compared invasive trophoblast chromatin accessibility with extravillous trophoblast cell accessibility. In comparing chromatin accessibility profiles between species, we found similarities in patterns of gene regulation and groups of motifs enriched in accessible regions. Finally, we identified a conserved gene regulatory network in invasive trophoblast cells. Our data, findings and analysis will facilitate future studies investigating regulatory mechanisms essential for the invasive trophoblast cell lineage.

Conservation at the uterine-placental interface.

The hemochorial placentation site is characterized by a dynamic interplay between trophoblast cells and maternal cells. These cells cooperate to establish an interface required for nutrient delivery to promote fetal growth. In the human, trophoblast cells penetrate deep into the uterus. This is not a consistent feature of hemochorial placentation and has hindered the establishment of suitable animal models. The rat represents an intriguing model for investigating hemochorial placentation with deep trophoblast cell invasion. In this study, we used single-cell RNA sequencing to characterize the transcriptome of the invasive trophoblast cell lineage, as well as other cell populations within the rat uterine-placental interface during early (gestation day [gd] 15.5) and late (gd 19.5) stages of intrauterine trophoblast cell invasion. We identified a robust set of transcripts that define invasive trophoblast cells, as well as transcripts that distinguished endothelial, smooth muscle, natural killer, and macrophage cells. Invasive trophoblast, immune, and endothelial cell populations exhibited distinct spatial relationships within the uterine-placental interface. Furthermore, the maturation stage of invasive trophoblast cell development could be determined by assessing gestation stage-dependent changes in transcript expression. Finally, and most importantly, expression of a prominent subset of rat invasive trophoblast cell transcripts is conserved in the invasive extravillous trophoblast cell lineage of the human placenta. These findings provide foundational data to identify and interrogate key conserved regulatory mechanisms essential for the development and function of an important compartment within the hemochorial placentation site that is essential for a healthy pregnancy.

Multicountry Spread of Influenza A(H1N1)pdm09 Viruses with Reduced Oseltamivir Inhibition, May 2023-February 2024.

Since May 2023, a novel combination of neuraminidase mutations, I223V + S247N, has been detected in influenza A(H1N1)pdm09 viruses collected in countries spanning 5 continents, mostly in Europe (67/101). The viruses belong to 2 phylogenetically distinct groups and display ≈13-fold reduced inhibition by oseltamivir while retaining normal susceptibility to other antiviral drugs.

Four-Month Rifapentine Regimens with or without Moxifloxacin for Tuberculosis.

BACKGROUND: Rifapentine-based regimens have potent antimycobacterial activity that may allow for a shorter course in patients with drug-susceptible pulmonary tuberculosis. METHODS: In an open-label, phase 3, randomized, controlled trial involving persons with newly diagnosed pulmonary tuberculosis from 13 countries, we compared two 4-month rifapentine-based regimens with a standard 6-month regimen consisting of rifampin, isoniazid, pyrazinamide, and ethambutol (control) using a noninferiority margin of 6.6 percentage points. In one 4-month regimen, rifampin was replaced with rifapentine; in the other, rifampin was replaced with rifapentine and ethambutol with moxifloxacin. The primary efficacy outcome was survival free of tuberculosis at 12 months. RESULTS: Among 2516 participants who had undergone randomization, 2343 had a culture positive for Mycobacterium tuberculosis that was not resistant to isoniazid, rifampin, or fluoroquinolones (microbiologically eligible population; 768 in the control group, 791 in the rifapentine-moxifloxacin group, and 784 in the rifapentine group), of whom 194 were coinfected with human immunodeficiency virus and 1703 had cavitation on chest radiography. A total of 2234 participants could be assessed for the primary outcome (assessable population; 726 in the control group, 756 in the rifapentine-moxifloxacin group, and 752 in the rifapentine group). Rifapentine with moxifloxacin was noninferior to the control in the microbiologically eligible population (15.5% vs. 14.6% had an unfavorable outcome; difference, 1.0 percentage point; 95% confidence interval [CI], -2.6 to 4.5) and in the assessable population (11.6% vs. 9.6%; difference, 2.0 percentage points; 95% CI, -1.1 to 5.1). Noninferiority was shown in the secondary and sensitivity analyses. Rifapentine without moxifloxacin was not shown to be noninferior to the control in either population (17.7% vs. 14.6% with an unfavorable outcome in the microbiologically eligible population; difference, 3.0 percentage points [95% CI, -0.6 to 6.6]; and 14.2% vs. 9.6% in the assessable population; difference, 4.4 percentage points [95% CI, 1.2 to 7.7]). Adverse events of grade 3 or higher occurred during the on-treatment period in 19.3% of participants in the control group, 18.8% in the rifapentine-moxifloxacin group, and 14.3% in the rifapentine group. CONCLUSIONS: The efficacy of a 4-month rifapentine-based regimen containing moxifloxacin was noninferior to the standard 6-month regimen in the treatment of tuberculosis. (Funded by the Centers for Disease Control and Prevention and others; Study 31/A5349 ClinicalTrials.gov number, NCT02410772.).

Predicting mental and psychomotor delay in very pre-term infants using machine learning.

BACKGROUND: Very preterm infants are at elevated risk for neurodevelopmental delays. Earlier prediction of delays allows timelier intervention and improved outcomes. Machine learning (ML) was used to predict mental and psychomotor delay at 25 months. METHODS: We applied RandomForest classifier to data from 1109 very preterm infants recruited over 20 years. ML selected key predictors from 52 perinatal and 16 longitudinal variables (1-22 mo assessments). SHapley Additive exPlanations provided model interpretability. RESULTS: Balanced accuracy with perinatal variables was 62%/61% (mental/psychomotor). Top predictors of mental and psychomotor delay overlapped and included: birth year, days in hospital, antenatal MgSO4, days intubated, birth weight, abnormal cranial ultrasound, gestational age, mom's age and education, and intrauterine growth restriction. Highest balanced accuracy was achieved with 19-month follow-up scores and perinatal variables (72%/73%). CONCLUSIONS: Combining perinatal and longitudinal data, ML modeling predicted 24 month mental/psychomotor delay in very preterm infants ½ year early, allowing intervention to start that much sooner. Modeling using only perinatal features fell short of clinical application. Birth year's importance reflected a linear decline in predicting delay as birth year became more recent. IMPACT: Combining perinatal and longitudinal data, ML modeling was able to predict 24 month mental/psychomotor delay in very preterm infants ½ year early (25% of their lives) potentially advancing implementation of intervention services. Although cognitive/verbal and fine/gross motor delays require separate interventions, in very preterm infants there is substantial overlap in the risk factors that can be used to predict these delays. Birth year has an important effect on ML prediction of delay in very preterm infants, with those born more recently (1989-2009) being increasing less likely to be delayed, perhaps reflecting advances in medical practice.

Alzheimer's polygenic risk scores are associated with cognitive phenotypes in Down syndrome.

INTRODUCTION: This study aimed to investigate the influence of the overall Alzheimer's disease (AD) genetic architecture on Down syndrome (DS) status, cognitive measures, and cerebrospinal fluid (CSF) biomarkers. METHODS: AD polygenic risk scores (PRS) were tested for association with DS-related traits. RESULTS: The AD risk PRS was associated with disease status in several cohorts of sporadic late- and early-onset and familial late-onset AD, but not in familial early-onset AD or DS. On the other hand, lower DS Mental Status Examination memory scores were associated with higher PRS, independent of intellectual disability and APOE (PRS including APOE, PRSAPOE , p = 2.84 × 10-4 ; PRS excluding APOE, PRSnonAPOE , p = 1.60 × 10-2 ). PRSAPOE exhibited significant associations with Aß42, tTau, pTau, and Aß42/40 ratio in DS. DISCUSSION: These data indicate that the AD genetic architecture influences cognitive and CSF phenotypes in DS adults, supporting common pathways that influence memory decline in both traits. HIGHLIGHTS: Examination of the polygenic risk of AD in DS presented here is the first of its kind. AD PRS influences memory aspects in DS individuals, independently of APOE genotype. These results point to an overlap between the genes and pathways that leads to AD and those that influence dementia and memory decline in the DS population. APOE ε4 is linked to DS cognitive decline, expanding cognitive insights in adults.

Citizen scientists' engagement in flood risk-related data collection: a case study in Bui River Basin, Vietnam.

Time constraints, financial limitations, and inadequate tools restrict the flood data collection in undeveloped countries, especially in the Asian and African regions. Engaging citizens in data collection and contribution has the potential to overcome these challenges. This research demonstrates the applicability of citizen science for gathering flood risk-related data on residential flooding, land use information, and flood damage to paddy fields for the Bui River Basin in Vietnam. Locals living in or around flood-affected areas participated in data collection campaigns as citizen scientists using self-investigation or investigation with a data collection app, a web form, and paper forms. We developed a community-based rainfall monitoring network in the study area using low-cost rain gauges to draw locals' attention to the citizen science program. Fifty-nine participants contributed 594 completed questionnaires and measurements for four investigated subjects in the first year of implementation. Five citizen scientists were active participants and contributed more than 50 completed questionnaires or measurements, while nearly 50% of citizen scientists participated only one time. We compared the flood risk-related data obtained from citizen scientists with other independent data sources and found that the agreement between the two datasets on flooding points, land use classification, and the flood damage rate to paddy fields was acceptable (overall agreement above 73%). Rainfall monitoring activities encouraged the participants to proactively update data on flood events and land use situations during the data collection campaign. The study's outcomes demonstrate that citizen science can help to fill the gap in flood data in data-scarce areas.

The transcription factors Junb and Fosl2 cooperate to regulate Cdh3 expression in 15P-1 Sertoli cells.

In Sertoli cells of the testis, cadherins (Cdh) are important cell-to-cell interaction proteins and contribute to the formation of the blood-testis barrier being essential for germ cells' protection. P-cadherin or Cdh3 is only expressed in Sertoli cells from embryonic to prepubertal development. Interestingly, the expression profile of Cdh3 correlates with that of activating protein-1 (AP-1) transcription factors during Sertoli cells development. To assess their potential implications in the regulation of Cdh3, different AP-1 transcription factors were overexpressed in 15P-1 Sertoli cells. We found that the overexpressions of Junb and Fosl2 activated Cdh3 promoter. ChIP-qPCR assay and luciferase reporter assay with 5' promoter deletions and site-directed mutagenesis confirmed the recruitment of Junb and Fosl2 to an AP-1 regulatory element at -47 bp in the proximal region of Cdh3 promoter in 15P-1 cells. These findings were further supported by histone modification markers and chromatin accessibility surrounding Cdh3 promoter in mouse testis. Moreover, the knockdowns of Junb and/or Fosl2 by siRNA decreased Cdh3 protein levels. Taken together, these data suggest that in 15P-1 Sertoli cells, the AP-1 family members Junb and Fosl2 are responsible for the regulation of Cdh3 expression, which requires the recruitment of both factors to the proximal region of the Cdh3 promoter.

Culture of primary human meibomian gland cells from surgically excised eyelid tissue.

Meibomian gland dysfunction is one of the most common ocular diseases, with therapeutic treatment being primarily palliative due to our incomplete understanding of meibomian gland (MG) pathophysiology. To progress in vitro studies of human MG, this study describes a comprehensive protocol, with detailed troubleshooting, for the successful isolation, cultivation and cryopreservation of primary MG cells using biopsy-size segments of human eyelid tissue that would otherwise be discarded during surgery. MG acini were isolated and used to establish and propagate lipid-producing primary human MG cells. The primary cell viability during culture procedure was maintained through the application of Rho-associated coiled-coil containing protein kinase inhibitor (Y-27632, 10 µM) and collagen I from rat tails. Transcriptomic analysis of differentiated primary human MG cells confirmed cell origin and revealed high-level expression of many lipogenesis-related genes such as stearoyl-CoA desaturase (SCD), ELOVL Fatty Acid Elongase 1 (ELOVL1) and fatty acid synthase (FASN). Primary tarsal plate fibroblasts were also successfully isolated, cultured and cryopreserved. Established primary human MG cells and tarsal plate fibroblasts presented in this study have potential for applications in 3D models and bioengineered tissue that facilitate research in understanding of MG biology and pathophysiology.

Insights into the synthesis strategies of plant-derived cyclotides.

Cyclotides are plant peptides characterized with a head-to-tail cyclized backbone and three interlocking disulfide bonds, known as a cyclic cysteine knot. Despite the variations in cyclotides peptide sequences, this core structure is conserved, underlying their most useful feature: stability against thermal and chemical breakdown. Cyclotides are the only natural peptides known to date that are orally bioavailable and able to cross cell membranes. Cyclotides also display bioactivities that have been exploited and expanded to develop as potential therapeutic reagents for a wide range of conditions (e.g., HIV, inflammatory conditions, multiple sclerosis, etc.). As such, in vitro production of cyclotides is of the utmost importance since it could assist further research on this peptide class, specifically the structure-activity relationship and its mechanism of action. The information obtained could be utilized to assist drug development and optimization. Here, we discuss several strategies for the synthesis of cyclotides using both chemical and biological routes.

Emerging waste-to-wealth applications of fly ash for environmental remediation: A review.

The considerable increase in world energy consumption owing to rising global population, intercontinental transportation and industrialization has posed numerous environmental concerns. Particularly, in order to meet the required electricity supply, thermal power plants for electricity generation are widely used in many countries. However, an annually excessive quantity of waste fly ash up to 1 billion tones was globally discarded from the combustion of various carbon-containing feedstocks in thermoelectricity plants. About half of the industrially generated fly ash is dumped into landfills and hence causing soil and water contamination. Nonetheless, fly ash still contains many valuable components and possesses outstanding physicochemical properties. Utilizing waste fly ash for producing value-added products has gained significant interests. Therefore, in this work, we reviewed the current implementation of fly ash-derived materials, namely, zeolite and geopolymer as efficient adsorbents for the environmental treatment of flue gas and polluted water. Additionally, the usage of fly ash as a catalyst support for the photodegradation of organic pollutants and reforming processes for the corresponding wastewater remediation and H2 energy generation is thoroughly covered. In comparison with conventional carbon-based adsorbents, fly ash-derived geopolymer and zeolite materials reportedly exhibited greater heavy metal ions removal and reached the maximum adsorption capacity of about 150 mg g-1. As a support for biogas reforming process, fly ash could enhance the activity of Ni catalyst with 96% and 97% of CO2 and CH4 conversions, respectively.

Factors influencing organised faecal occult blood test screening participation in culturally and linguistically diverse populations: a scoping review.

OBJECTIVE: This review aims to provide a comprehensive overview of the literature examining factors influencing participation in organised faecal occult blood test (FOBT) screening programmes in culturally and linguistically diverse populations. This article addresses gaps in the literature by providing a mixed methods review of the multilevel influences on FOBT screening in culturally and linguistically diverse (CALD) populations. This review was guided by the question "What are the factors influencing participation in organised FOBT screening programs in CALD populations?" STUDY DESIGN: Scoping review. METHODS: A scoping review methodology was used to summarise the available evidence. A thematic analysis of the included studies was undertaken to identify factors influencing organised FOBT screening participation in CALD populations from the literature. RESULTS: FOBT screening participation was lower by ethnicity, religion, birthplace and language spoken. Barriers to screening included, faecal aversion, fatalism, fear of cancer, language and literacy barriers, difficulty accessing translated materials and low colorectal screening knowledge and awareness. CALD populations also had lower perceived benefits, susceptibility and cues to action, higher perceived barriers and greater perceived external health locus control than non-CALD populations. Facilitators of screening included positive attitudes to screening, general practitioner recommendations and social support. Group education sessions and narrative-based screening information were found to increase screening participation. CONCLUSION: This review highlights the range of interrelated factors influencing participation in organised FOBT screening programmes in CALD populations and proposes multicomponent interventions to address low screening uptake. Features of successful community-level interventions should be explored further. Narratives show promise for engaging CALD populations. Accessibility of screening information should be addressed at the system level. Leveraging the general practitioner relationship in promoting FOBT screening programmes may also be an effective strategy to target 'hard-to-reach' populations.

Synthesis of a Grease Thickener from Cashew Nut Shell Liquor.

Thickener, also known as a gelling agent, is a critical component of lubricating greases. The most critical property of thickener, temperature resistance, is determined by the molecular structure of the compounds. Currently, all high-temperature-resistant thickeners are based on 12-hydroxystearic acid, which is exclusively produced from castor oil. Since castor oil is also an important reagent for other processes, finding a sustainable alternative to 12-hydroxystearic acid has significant economic implications. This study synthesises an alternative thickener from abundant agricultural waste, cashew nut shell liquor (CNSL). The synthesis and separation procedure contains three steps: (i) forming and separating calcium anacardate by precipitation, (ii) forming and separating anacardic acid (iii) forming lithium anacardate. The obtained lithium anacardate can be used as a thickener for lubricating grease. It was found that the recovery of anacardic acid was around 80%. The optimal reaction temperature and time conditions for lithium anacardate were 100 °C and 1 h, respectively. The method provides an economical alternative to castor and other vegetable oils. The procedure presents a simple pathway to produce the precursor for the lubricating grease from agricultural waste. The first reaction step can be combined with the existing distillation of cashew nut shell processing. An effective application can promote CNSL to a sustainable feedstock for green chemistry. The process can also be combined with recycled lithium from the spent batteries to improve the sustainability of the battery industry.

New microbial electrosynthesis system for methane production from carbon dioxide coupled with oxidation of sulfide to sulfate.

Microbial electrosynthesis system (MES) is a promising method that can use carbon dioxide, which is a greenhouse gas, to produce methane which acts as an energy source, without using organic substances. However, this bioelectrical reduction reaction can proceed at a certain high applied voltage when coupled with water oxidation in the anode coated with metallic catalyst. When coupled with the oxidation of HS- to SO42-, methane production is thermodynamically more feasible, thus implying its production at a considerably lower applied voltage. In this study, we demonstrated the possibility of electrotrophic methane production coupled with HS- oxidation in a cost-effective bioanode chamber in the MES without organic substrates at a low applied voltage of 0.2 V. In addition, microbial community analyses of biomass enriched in the bioanode and biocathode were used to reveal the most probable pathway for methane production from HS- oxidation. In the bioanode, electroautotrophic SO42- production accompanied with electron donation to the electrode is performed mainly by the following two steps: first, incomplete sulfide oxidation to sulfur cycle intermediates (SCI) is performed; then the produced SCI are disproportionated to HS- and SO42-. In the biocathode, methane is produced mainly via H2 and acetate by electron-accepting syntrophic bacteria, homoacetogens, and acetoclastic archaea. Here, a new eco-friendly MES with biological H2S removal is established.

Child Melioidosis Deaths Caused by Burkholderia pseudomallei-Contaminated Borehole Water, Vietnam, 2019.

Within 8 months, 3 children from 1 family in northern Vietnam died from melioidosis. Burkholderia pseudomallei of the same sequence type, 541, was isolated from clinical samples, borehole water, and garden and rice field soil. Boreholes should be properly constructed and maintained to avoid B. pseudomallei contamination.

Comparative efficacy and safety of pharmacologic interventions to prevent mother-to-child transmission of hepatitis B virus: a systematic review and network meta-analysis.

OBJECTIVE: This study investigated the efficacy and safety of pharmacologic interventions to prevent vertical transmission of the hepatitis B virus. DATA SOURCES: Medline, Cochrane, and Scopus databases were searched up to October 28, 2020. STUDY ELIGIBILITY CRITERIA: All randomized controlled trials reporting vertical hepatitis B virus transmission with pharmacologic intervention were included. METHODS: Risk of bias was assessed using the Cochrane Risk-of-Bias tool, version 2. Treatment efficacy was estimated using stratified network meta-analysis on the basis of maternal hepatitis B envelope antigen status. RESULTS: Nineteen studies were included for mothers positive for hepatitis B surface and envelope antigens. Pooling indicated that a combination of hepatitis B vaccination and hepatitis B immunoglobulin in infants significantly reduced transmission risk compared with vaccination alone, with a risk ratio of 0.52 (95% confidence interval; 0.30-0.91). Only the addition of maternal tenofovir disoproxil fumarate, but not telbivudine, lamivudine, or maternal hepatitis B immunoglobulin further reduced transmission risk compared with a combination of hepatitis B vaccination and hepatitis B immunoglobulin in infants, with a pooled risk ratio of 0.10 (0.03-0.35). Twelve studies conducted in mothers with hepatitis B surface antigen positivity and mixed, unknown, or negative hepatitis B envelope antigen status provided limited evidence to suggest that maternal hepatitis B immunoglobulin combined with hepatitis B vaccination and immunoglobulin in infants was the likely best treatment, but this failed to reach statistical significance compared with a combination of hepatitis B vaccination and immunoglobulin in infants. Similarly, infant hepatitis B immunoglobulin, added to vaccination, likely provides additional benefit but failed to reach statistical significance. CONCLUSION: A combination of hepatitis B vaccination and immunoglobulin in infants is the cornerstone for prevention of vertical transmission for mothers positive for both hepatitis B surface and envelope antigens. The addition of maternal tenofovir to this infant combination regimen was considered the likely most effective treatment. For infants of mothers with hepatitis B surface antigen positivity and mixed, unknown, or negative hepatitis B envelop antigen status, no additional agents provided further benefit beyond hepatitis B vaccination alone.

Influenza Activity and Composition of the 2022-23 Influenza Vaccine - United States, 2021-22 Season.

Before the emergence of SARS-CoV-2, the virus that causes COVID-19, influenza activity in the United States typically began to increase in the fall and peaked in February. During the 2021-22 season, influenza activity began to increase in November and remained elevated until mid-June, featuring two distinct waves, with A(H3N2) viruses predominating for the entire season. This report summarizes influenza activity during October 3, 2021-June 11, 2022, in the United States and describes the composition of the Northern Hemisphere 2022-23 influenza vaccine. Although influenza activity is decreasing and circulation during summer is typically low, remaining vigilant for influenza infections, performing testing for seasonal influenza viruses, and monitoring for novel influenza A virus infections are important. An outbreak of highly pathogenic avian influenza A(H5N1) is ongoing; health care providers and persons with exposure to sick or infected birds should remain vigilant for onset of symptoms consistent with influenza. Receiving a seasonal influenza vaccine each year remains the best way to protect against seasonal influenza and its potentially severe consequences.