Identification of a novel TBX5 c.755 + 1 G > A variant and related pathogenesis in a family with Holt-Oram syndrome.

The proband with congenital heart disease and abnormal thumb was clinically diagnosed as Holt-Oram syndrome (HOS). A novel variant, T-box transcription factor 5 (TBX5) c.755 + 1 G > A, was identified in the proband via whole exome sequencing and validated using Sanger sequencing. Pedigree analysis and clinical examinations revealed three/seven individuals over three generations within the family, with features suggestive of HOS. Deep amplicon sequencing confirmed that the allele frequencies of the novel variant in the proband (III-1), her brother (III-2), and her mother (II-2) were 50%, 48.3%, and 38.1%, respectively, indicating that III-1 and III-2 harbored heterozygous variants, while II-2 harbored mosaic heterozygous variants. The minigene splicing assay showed that the novel variant affected the normal splicing of exon 7, resulting in the production of abnormal TBX5 transcripts. Reverse transcription-quantitative polymerase chain reaction and western blot analyses revealed that the novel variant upregulated TBX5 expression at the transcriptional and translational levels. Nuclear localization assay demonstrated impaired nuclear localization of the mutant TBX5. Cell viability assay revealed the inhibition of cell activity by the mutant TBX5. Our findings indicate that the novel variant was potentially induced HOS, probably by causing aberrant splicing, reducing the enrichment of nuclear TBX5 protein, and inhibiting cellular proliferation.

Detection of partial deletion and mosaicism using quantitative fluorescent polymerase chain reaction: Case reports and a review of the literature.

BACKGROUND: Aneuploidy of chromosomes 13, 18, 21, X, and Y can be detected by the quantitative fluorescence polymerase chain reaction (QF-PCR) performed with short tandem repeat (STR) markers. Although QF-PCR is designed to detect whole chromosome trisomy, the partial deletion or mosaic of chromosomes may also be detected. METHODS: Partial deletion or mosaic of chromosomes in three cases was detected by QF-PCR. Karyotyping and chromosome microarray analysis(CMA) were performed. We further reviewed the clinical utility of QF-PCR in detecting mosaicisms and deletions/duplications. RESULTS: QF-PCR demonstrated structurally abnormal 21, X, and Y chromosomes in primary amniotic cells. QF-PCR results in these three cases showed abnormal peak height/peak area, which could not be interpreted according to the kit instructions. QF-PCR results suggested that there were partial deletions or mosaicism, which were confirmed by karyotyping and CMA. CONCLUSION: In addition to detecting trisomies of whole chromosomes, QF-PCR can also detect deletion and mosaicism of chromosomes 13, 18, 21, X, and Y, which could suggest the presence of copy number variants (CNVs). Additional testing with genetic technologies, such as karyotyping or microarrays, is recommended when an uninformative pattern is suspected.

δ-Thalassemia with Complete Absence of Hb A2 in a Chinese Family.

A Chinese family with δ-thalassemia (δ-thal) was found, in which the daughter is homozygous for δ-thal (HBD: c.-127T>C) with complete deficiency of Hb A2 and the mother is a heterozygote with low level of Hb A2. The father, however, is a heterozygote with a normal Hb A2 value due to coinheritance of a ß-thalassemia (ß-thal). Although no abnormal clinical or hematological findings were noted in the individuals with δ-thal, one should keep in mind that ß-thal can be missed during routine preliminary screening when ß-thal and δ-thal coexist in a subject.

Screening and Diagnosis of Rare Thalassemia Variants: Is Third-Generation Sequencing Enough?

CONTEXT.­: Rare thalassemia subtypes are often undiagnosed because conventional testing methods can only identify 23 common types of α- and ß-thalassemia. OBJECTIVE.­: To assess a comprehensive approach for the screening and diagnosis of rare thalassemia. DESIGN.­: The study cohort included 72 individuals with suspected rare thalassemia variants. Screening was conducted by next-generation sequencing (NGS) combined with third-generation sequencing (TGS) and chromosomal microarray analysis (CMA)/copy number variation sequencing. RESULTS.­: Of the 72 individuals with suspected rare thalassemia, 49 had rare α- or ß-gene variants. NGS combined with gap polymerase chain reaction detected a total of 42 cases, resulting in a positive detection rate of 58.3%. Additionally, 4 α-globin genetic deletions were identified by TGS, which increased the variant detection rate by 5.6%. Two samples with a microdeletion of chromosome 16 or 11 were detected by CMA, which increased the detection rate by 2.8%. For one sample, reanalysis of the NGS and TGS data confirmed the presence of the ß41-42/ßN and ßN/ßN mosaic. The HBB:c.315 + 2delT mutation was initially reported in Guangdong Province, China. Two HBB gene mutations (HBB:c.315 + 5G>C and HBB:c.295G>A) and 4 rare HBA gene deletions (-11.1, -α27.6, -α2.4, and -α21.9) were initially identified in the Zhonshan region. The hematologic phenotypes of all rare cases in this study were clarified. CONCLUSIONS.­: Rare thalassemia variants are more common than previously thought. Despite advancements in TGS, there is still no foolproof method for detection of all types of thalassemia. Thus, a comprehensive approach is necessary for accurate screening and diagnosis of rare thalassemia variants.

Chromosomal microarray analysis for prenatal diagnosis of uniparental disomy: a retrospective study.

BACKGROUND: Chromosomal microarray analysis (CMA) is a valuable tool in prenatal diagnosis for the detection of chromosome uniparental disomy (UPD). This retrospective study examines fetuses undergoing invasive prenatal diagnosis through Affymetrix CytoScan 750 K array analysis. We evaluated both chromosome G-banding karyotyping data and CMA results from 2007 cases subjected to amniocentesis. RESULTS: The detection rate of regions of homozygosity (ROH) ≥ 10 Mb was 1.8% (33/2007), with chromosome 11 being the most frequently implicated (17.1%, 6/33). There were three cases where UPD predicted an abnormal phenotype based on imprinted gene expression. CONCLUSION: The integration of UPD detection by CMA offers a more precise approach to prenatal genetic diagnosis. CMA proves effective in identifying ROH and preventing the birth of children affected by imprinting diseases.

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To explore the temporal and spatial variations in phytoplankton community in small estuaries, we collected surface water samples from Yongjiang River estuary during wet, normal, and dry seasons and determined the main driving factors of phytoplankton community. A total of 358 species belonging to nine phyla and 123 genera were identified in all seasons. During wet, normal, and dry seasons, species number was 276, 154 and 151, and the abundance was (170.45±225.43)×103, (51.92±30.28)×103 and (31.65±12.79)×103 cells·L-1, respectively. Diatoms dominated the phytoplankton community, and the main dominant species were Cyclotella meneghiniana, Skeletonema costatum, and Paralia sulcata. Shannon diversity and Pielou evenness indices decreased from inside mouth to outside mouth in wet season, but there was no obvious spatial difference in normal season or dry season. Results of non-metric multidimensional scaling analysis and analysis of similarities showed that phytoplankton community composition differed significantly among different regions (inside, at and outside mouth) and different seasons. In wet season, phytoplankton abundance was significantly positively correlated with temperature, dissolved inorganic nitrogen, and dissolved reactive phosphorus, but significantly negatively correlated with salinity. In normal season, phytoplankton abundance was significantly negatively correlated with temperature. In dry season, it was not significantly correlated with environmental factors. Results of redundancy analysis showed that temperature, salinity, ammonium and dissolved reactive phosphorus explained the variations in phytoplankton community by 19.5%, 11.9%, 9.4% and 8.2%, respectively. These results revealed high dominance of diatoms and the main driving factors (temperature, salinity and nutrients) of phytoplankton community in Yongjiang River estuary.

Ten years' experience in prenatal diagnosis of α-thalassemia in a municipal hospital and retrospective analysis of ultrasonic abnormalities.

OBJECTIVE: This study reviewed and analyzed the prenatal diagnosis experience of thalassemia in our center over the past decade and the abnormal ultrasonic characteristics of fetuses with hemoglobin (Hb) Bart's hydrops fetalis. METHODS: Pregnant women and their partners who tested positive for α0-thalassemia or were diagnosed with thalassemia intermedia (HbH diseases) underwent genetic counseling, and a prenatal diagnostic procedure for α-thalassemia was recommended. Ultrasonography was performed before prenatal diagnosis. RESULTS: Invasive prenatal α-thalassemia diagnosis and ultrasonography were performed in 1049 patients at risk for Hb Bart's hydrops fetalis syndrome at our hospital from 2012 to 2021. Chorionic villus sampling (CVS) was performed in 58 cases (5.5%), amniocentesis in 902 cases (86%), and cordocentesis in 89 cases (8.5%). Hb Bart's hydrops fetalis syndrome was diagnosed in 280 fetuses. The most common body cavity effusion was pericardial effusion, ascites, and fetal systemic edema. CONCLUSIONS: The extensive experience at our center shows that carrier screening, molecular diagnostics, genetic counseling, and prenatal diagnosis are effective measures to prevent Hb Bart's hydrops fetalis syndrome. The ultrasonographic abnormalities in fetuses with Hb Bart's hydrops are mainly caused by an increase in cardiac output, which leads to the body cavity effusion from various organs.

Identification of compound heterozygous deletion of the WWOX gene in WOREE syndrome.

BACKGROUND: Biallelic loss-of-function variants in WWOX cause WWOX-related epileptic encephalopathy (WOREE syndrome), which has been reported in 60 affected individuals to date. In this study, we report on an affected individual with WOREE syndrome who presented with early-onset refractory seizures and global neurodevelopmental delay and died at the age of two and a half years. METHODS: We present clinical and molecular findings in the affected individual, including biallelic pathogenic variants in the WWOX gene. We employed different molecular approaches, such as whole exome sequencing, quantitative real-time polymerase chain reaction (qPCR), and whole-genome sequencing, to identify the genetic variants. The breakpoints were determined through gap PCR and Sanger sequencing. RESULT: Whole exome sequencing revealed homozygous exon 6 deletion in the WWOX gene in the proband. Quantitative real-time PCR confirmed that the parents were heterozygous carriers of exon 6 deletion. However, using whole-genome sequencing, we identified three larger deletions (maternal allele with exon 6-8 deletion and paternal allele with two deletions in proximity one in intron 5 and the other in exon 6) involving the WWOX gene in the proband, with deletion sizes of 13,261 bp, 53,904 bp, and 177,200 bp. The exact breakpoints were confirmed through gap PCR and Sanger sequencing. We found that the proband inherited the discontinuous deletion of intron 5 and exon 6 from the father, and the exons 6-8 deletion from the mother using gap PCR. CONCLUSION: Our findings extend the variant spectrum of WOREE syndrome and support the critical role of the WWOX gene in neural development.

Case report: A case report and literature review of complete trisomy 9.

Complete trisomy 9 is a rare and lethal chromosomal anomaly characterized by multisystem dysmorphism and central nervous system (CNS) malformations. This study presents a case of complete trisomy 9 with an unusual phenotypic association and investigates the genetic pathways involved in this chromosomal abnormality. Trisomy 9 leads to a wide range of organ abnormalities, and this research contributes to a better understanding of the phenotype associated with this rare aneuploidy. The literature on the phenotypes of fetuses with various systems affected by complete trisomy 9 was reviewed and summarized. Correct diagnosis and appropriate counseling based on the characteristics of previous reports of fetuses with trisomy 9 is essential in maternity care and clinical management. To provide guidance and help for clinical diagnosis, this study aimed to explore the clinical and genetic characteristics of trisomy 9 syndrome to improve clinicians' understanding of the disease.

Clinical implications of haemoptysis in patients with pulmonary arterial hypertension.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a disabling disease that may result in haemoptysis. Patients with congenital heart disease associated PAH (CHD-APAH) may have a survival advantage when compared with patients with other types of PAH presenting with haemoptysis. The effects of aetiology and subsequent management choice of haemoptysis in PAH patients is not well-defined. METHODS: We conducted outcome analysis in CHD-APAH vs. all other subtypes of PAH patients presenting with haemoptysis to The Methodist Hospital. Twenty-one patients were identified, 13 patients in the CHD-APAH group and eight patients in the non-CHD group. We evaluated outcomes related to treatment (bronchial artery embolisation (BAE) vs. conservative management), hospital length of stay, mortality rates and survival in this cohort. RESULTS: The CHD-APAH and non-CHD groups had similar baseline demographic, haemodynamic and laboratory values except BMI was higher in the non-CHD group and haematocrit was higher in the CHD-APAH group. Twenty-eight-day mortality (0% vs. 31%) and 1-year mortality (0% vs. 54%) was lower in the CHD-APAH patients as compared with non-CHD group. A statistically significant difference was found in the survival rate in favour of CHD-APAH group for the total follow-up period (p = 0.02). Although not statistically significant, patients treated with BAE had shorter length of stay (4.0 days ± 4.0 vs. 13.7 days ± 22.5; p = 0.26). There was recurrent haemoptysis in 43% of patients treated with BAE. CONCLUSION: Haemoptysis in PAH patients is a serious event with a high mortality rate. CHD-APAH seems to confer a survival advantage, independent of therapy utilised. Termination of haemoptysis with BAE is rapid with relatively few complications except for frequent re-bleeding episodes. Further studies are needed to determine the risk factors that may predispose PAH patients to excessive mortality from haemoptysis and to identify an optimal therapeutic modality.

Study on Correlation of Mechanical and Thermal Properties of Coal-Based Carbon Foam with the Weight Loss Rate after Oxidation.

With the increasing demand for high temperature-resistant heat insulation materials for hypersonic vehicles, carbon foam has been studied extensively, and its mechanical and thermal properties have been fully researched, but the oxidation behavior of carbon foams during service and the change in their properties after oxidation are rarely studied. This paper studied the relationship between both mechanical and thermal properties and oxidation degree of two kinds of foams, coal-based carbon foam and antioxidant coal-based carbon foam with chemical vapor deposition of SiC particles. The variation trend for the two kinds of foam was the same. When the oxidation degree was less than 15%, the compression modulus and strength weakened with the increase in weight loss rate, but the thermal conductivity decreased with the increase in weight loss rate, which was a favorable influence for the thermal protection system. The mechanical and thermal properties had a linear relationship with the weight loss rate, but the slope was different between 0% to 10% and 10% to 15%. The microscopic mechanism of these changes was also analyzed.

Biostatistics of VHL-Gene Transfection in the Health Informatics Analysis of Renal Cell Carcinoma.

OBJECTIVE: In this paper, we study the role of the VHL gene in regulating the proliferation and apoptosis of renal cell carcinoma, as well as the safety and transfection efficiency of ultrasound microbubble gene transfection technology. METHOD: We use kidney cancer cell lines as an in vitro research object and apply ultrasound microbubble gene transfection technology to transfect the VHL gene into kidney cancer cell line (786-0). The proliferation and apoptosis of cells were measured to clarify the inhibitory effect of the VHL gene in renal cell carcinoma. After that, pEGFP-VHL was transfected using ultrasonic microbubble and liposome gene transfection techniques, respectively, and the transfection efficiency was measured by immunofluorescence. RESULTS: Compared with untreated and 786-0 cells that are transfected with empty vector, the expression level of VHL gene mRNA in 786-0 cells that are transfected with pcDNA3.1-VHL was significantly increased, and the cell growth inhibition rate was significantly higher. The rate of apoptosis increased significantly. Transfection efficiency of the pEGFP-VHL gene after transfection of 786-0 cells for 48 h: control group 0, liposome group (35.55 ± 2.77) %, ultrasound microbubble group (18.27 ± 2.83) %, and two transfection methods on cells. There is no significant difference in the impact of vitality. CONCLUSION: VHL gene expression can significantly inhibit the proliferation ability of renal cancer cell line 786-0 and promote its apoptosis. VHL gene is a potential target for gene therapy of kidney cancer.

Delay-Dependent Switching Approaches for Stability Analysis of Two Additive Time-Varying Delay Neural Networks.

This article analyzes the exponentially stable problem of neural networks (NNs) with two additive time-varying delay components. Disparate from the previous solutions on this similar model, switching ideas, that divide the time-varying delay intervals and treat the small intervals as switching signals, are introduced to transfer the studied problem into a switching problem. Besides, delay-dependent switching adjustment indicators are proposed to construct a novel set of augmented multiple Lyapunov-Krasovskii functionals (LKFs) that not only satisfy the switching condition but also make the suitable delay-dependent integral items be in the each corresponding LKF based on each switching mode. Combined with some switching techniques, some less conservativeness stability criteria with different numbers of switching modes are obtained. In the end, two simulation examples are performed to demonstrate the effectiveness and efficiency of the presented methods comparing other available ones.

Exponential Stability of Mixed Time-Delay Neural Networks Based on Switching Approaches.

Neural networks (NNs) have been deeply studied due to their wide applicability. Since time delays are unavoidable in reality, it is basic and crucial for all applications based on NNs to guarantee system stability under the influence of mixed time delays. To better exploit the variation information of time delay, we introduce the switching idea and approaches into mixed time-delay NNs to solve the stability problem. First, the considered mixed time-delay NNs are modeled as the switched NNs by dividing the two classes of time delays, discrete and distributed time delays, into some variable intervals and combining these intervals as new switching modes. With the help of mode-dependent average dwell-time switching, Lyapunov theory, and mathematical techniques, several exponential stability criteria on the modeled switched systems containing different modes are obtained. Moreover, via introducing the mathematical condition of the unstable subsystem in the switching system, a less conservativeness condition on the exponential stability of the modeled NNs is proposed. We perform three examples for testifying the validity of the proposed methods over existing ones.

Next-generation sequencing reveals a case of Norrie disease in a child with bilateral ocular malformation.

A Norrie disease protein gene (NDP) variant, c.174 + 1G > A, was found in a Chinese family through next-generation sequencing and verified with Sanger sequencing. A case of Norrie disease was reported in the first child, and the symptoms were consistent with the results of gene sequencing. The child's mother, who was pregnant at the time, was found to be a carrier of the identified pathogenic variant. To determine if the fetus carried the same disease-causing variant, prenatal examination and prenatal diagnosis were conducted. The fetus had biocular vitreous abnormalities and complete retinal abnormalities. Genetic testing showed that the fetus had maternally inherited the NDP gene variant found in the proband. It was concurrently confirmed that the NDP gene variant led to the deletion of 246 bp at the 3' end of exon 2, resulting in the deletion of the initiation codon and the occurrence of disease. Our study suggests that the diagnosis of rare diseases through next-generation sequencing, combined with prenatal ultrasound and prenatal diagnosis, can help families with known familial genetic diseases. Furthermore, the findings of this study broaden the known genetic spectrum of Norrie disease.

Exponentially Synchronous Results for Delayed Neural Networks With Leakage Delay via Switched Delay Idea and AED-ADT Method.

Time delay has always been one of the main factors affecting the application performance of neural network (NN) systems, and dynamic performance research of NNs with time delays has been the focus of many scholars in recent years. This article enquires into the exponentially synchronous problem of switched delayed NNs with time delay in the leakage term. Adopting an unusual form from a common switched system, the switching modes of the switched delayed NNs system in this article are dependent on time delays. In the first place, the master, slave, and error NNs models are reconstructed into the switched form by introducing the switched delay idea. Then with the help of the admissible edge-dependent average dwell time (AED-ADT) method and delay-dependent switching adjustment indicators, a novel set of generalized delay-mode-dependent multiple Lyapunov-Krasovskii functionals (MLKFs) is built for analyzing the cases where a state-feedback controller exists and does not exist in the model, and where parts of LKFs may increase during the period when the corresponding subsystems are activated. For these cases, several effective exponential synchronization criteria and switching laws are presented accordingly. At last, the verification of the theoretical results is shown through a few examples.

Real-World Cost of Nasal Polyps Surgery and Risk of Major Complications in the United States: A Descriptive Retrospective Database Analysis.

Background: Endoscopic nasal polyp (NP) surgery is a treatment option for patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Previous studies report NP surgery costs of $8000-13,000 and risk of major complications of NP surgery of ~0.1-1%. Limited contemporary data for costs and complications associated with NP surgery in US clinical practice are available. Methods: IQVIA PharMetrics Plus claims data were used to identify patients with NP surgery in 2019 with ≥3 years continuous baseline health-plan enrollment prior to index date (date of first eligible NP surgery) and ≥30 days continuous enrollment after index (follow-up). In this descriptive analysis, total costs of NP surgery were estimated as all medical costs on the index date (or during the entire hospital stay for patients who received surgery in the inpatient setting). Total medical costs (all-cause) were estimated for all medical services occurring from the index date to the index date +9 or +29 days (10-day and 30-day). Major complication was defined as cerebrospinal fluid (CSF) leak, orbital injury, or major hemorrhage within 30 days of index. Results: Of 6311 patients, median age was 46 years (interquartile range: 34-56); 59.7% were male; 88.2% had no NP surgery in the prior 3 years; 63.7% had allergic rhinitis, and 37.1% had asthma. Mean (SD) total medical cost of surgery was $14,697 (11,679) and mean (SD) 10-day total medical cost was $15,401 (11,968). Major complications occurred in 102 (1.7%) patients. Total medical costs and 10-day costs were higher in patients with major complications than those without ($23,605 [19,264] vs $15,251 [11,741]). Conclusion: In this descriptive analysis, NP surgery costs and rates of major surgical complications were updated using recent real-world data in the US. Results indicated that NP surgery complication rates were numerically higher than previously reported.

Prenatal diagnosis of Bardet­Biedl syndrome due to novel variants in the BBS10 gene in a fetus with multiple anomalies: A case report.

Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder characterized by obesity, mental retardation, retinal dystrophy, hypogenitalism and renal and polydactyly malformations. The last two malformations may be observed antenatally and are highly variable, making the prenatal diagnosis of BBS challenging. The present study investigated the molecular etiology of BBS and validated a method for prenatal diagnosis. A Chinese couple who had conceived two fetuses with multiple malformations, including hyperechogenic kidneys, polydactyly, cardiac malformation and abdominal abnormalities, presented at the Prenatal Diagnosis Center of Boai Hospital of Zhongshan Affiliated to Southern Medical University (Zhongshan, China) in November 2018. BBS was suspected and whole-exome sequencing was performed for the second fetus. Two novel compound heterozygous variants were detected in the BBS10 gene, c.784_785delGA from the father and c.1812dupT from the mother, which are probably causative of the pathogenesis of BBS. This finding provided a basis for genetic counseling and prenatal diagnosis for the couple and enriched the variation spectrum of the BBS10 gene. The ultrasonic findings of the fetal abdomen are the first reported in fetuses with BBS, expanding the antenatal phenotypes of BBS.

Real-world effectiveness of casirivimab and imdevimab among patients diagnosed with COVID-19 in the ambulatory setting: a retrospective cohort study using a large claims database.

OBJECTIVE: To assess the real-world effectiveness of casirivimab and imdevimab (CAS+IMD) versus no COVID-19 antibody treatment among patients diagnosed with COVID-19 in the ambulatory setting, including patients diagnosed during the Delta-dominant period prior to Omicron emergence. DESIGN: Retrospective cohort study. SETTING: Komodo Health closed claims database. PARTICIPANTS: 13 273 128 patients diagnosed with COVID-19 (December 2020 through September 2021) were treated with CAS+IMD or untreated but treatment eligible under the Emergency Use Authorization (EUA). Each treated patient was exact and propensity score matched without replacement to up to five untreated EUA-eligible patients. INTERVENTIONS: CAS+IMD. PRIMARY AND SECONDARY OUTCOME MEASURES: Composite endpoint of 30-day all-cause mortality or COVID-19-related hospitalisation. Kaplan-Meier estimators were used to calculate outcome risks overall and across subgroups: age, COVID-19 vaccination status, immunocompromised status, and timing of diagnosis (December 2020 to June 2021, and July to September 2021). Cox proportional hazards models were used to estimate adjusted HRs (aHRs) and 95% CIs. RESULTS: Among 75 159 CAS+IMD-treated and 1 670 338 EUA-eligible untreated patients, 73 759 treated patients were matched to 310 688 untreated patients; matched patients were ~50 years, ~60% were women and generally well balanced across risk factors. The 30-day risk of the composite outcome was 2.1% and 5.2% in the CAS+IMD-treated and CAS+IMD-untreated patients, respectively; equivalent to a 60% lower risk (aHR 0.40; 95% CI, 0.38 to 0.42). The effect of CAS+IMD was consistent across subgroups, including those who received a COVID-19 vaccine (aHR 0.48, 95% CI, 0.41 to 0.56), and those diagnosed during the Delta-dominant period (aHR 0.40, 95% CI, 0.38 to 0.42). CONCLUSIONS: The real-world effectiveness of CAS+IMD is consistent with the efficacy for reducing all-cause mortality or COVID-19-related hospitalisation reported in clinical trials. Effectiveness is maintained across patient subgroups, including those prone to breakthrough infections, and was effective against susceptible variants including Delta. .