How have US colorectal cancer mortality trends changed in the past 20 years?

In the last two decades, colorectal cancer (CRC) mortality has been decreasing in the United States. However, the mortality trends for the different subtypes of CRC, including different sides of colon, rectosigmoid, and rectal cancer remain unclear. We analyzed the mortality trends of different subtypes of CRC based on Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research data from 1999 to 2020. We calculated age-adjusted mortality rates (AAMR) per 100,000 individuals and examined the trends over time by estimating the average annual percent change (AAPC) using the Joinpoint Regression Program. Our study shows that the overall CRC rates decreased significantly from 26.42 to 15.98 per 100,000 individuals, with an AAPC of -2.41. However, the AAMR of rectosigmoid cancer increased significantly from 0.82 to 1.08 per 100,000 individuals, with the AAPC of +1.10. Men and Black individuals had the highest AAMRs respectively (23.90 vs. 26.93 per 100,000 individuals). The overall AAMR of CRC decreased for those aged ≥50 years but increased significantly from 1.02 to 1.58 per 100,000 individuals for those aged 15-49 years, with an AAPC of +0.75. Rural populations had a higher AAMR than the urban populations (22.40 vs. 19.60 per 100,000 individuals). Although overall CRC mortality declined, rising trends in young-onset CRC and rectosigmoid cancer warrant attention. Disparities persist in terms of sex, race, and geographic region, and urbanization level, emphasizing the need for targeted public health measures.

Gender, Racial, and Geographical Disparities in Malignant Brain Tumor Mortality in the USA.

INTRODUCTION: Malignant brain tumors are malignancies which are known for their low survival rates. Despite advancements in treatments in the last decade, the disparities in malignant brain cancer mortality among the US population remain unclear. METHODS: We analyzed death certificate data from the US CDC WONDER from 1999 to 2020 to determine the longitudinal trends of malignant brain tumor mortality. Malignant brain tumor (ICD-10 C71.0-71.9) was listed as the underlying cause of death. Age-adjusted mortality rates (AAMRs) per 100,000 individuals were calculated by standardizing the AAMR to the year 2000 US population. RESULTS: From 1999 to 2020, there were 306,375 deaths due to malignant brain tumors. The AAMR decreased from 5.57 (95% CI, 5.47-5.67) per 100,000 individuals in 1999 to 5.40 (95% CI, 5.31-5.48) per 100,000 individuals in 2020, with an annual percent decrease of -0.05 (95% CI, -0.22, 0.12). Whites had the highest AAMR (6.05 [95% CI, 6.02-6.07] per 100,000 individuals), followed by Hispanics (3.70 [95% CI, 3.64-3.76]) per 100,000 individuals, blacks (3.09 [95% CI, 3.04-3.14] per 100,000 individuals), American Indians (2.82 [95% CI, 2.64-3.00] per 100,000 individuals), and Asians (2.44 [95% CI, 2.38-2.50] per 100,000 individuals). The highest AAMRs were reported in the Midwest region (5.58 [95% CI, 5.54-5.62] per 100,000 individuals) and the rural regions (5.66 [95% CI, 5.61-5.71] per 100,000 individuals). CONCLUSIONS: Our study highlights the mortality disparity among different races, geographic regions, and urbanization levels. The findings underscore the importance of addressing the disparities in malignant brain tumors that existed among males, white individuals, and rural populations.

Racial and Geographic Differences in Endometrial Cancer Death.

INTRODUCTION: In the USA, endometrial cancer incidence rose by 4.5% annually from 1999 to 2015, reaching 18 per 100,000 women, with a disproportionate impact on African American women. Despite advancements in endometrial cancer research, racial disparities in mortality rates persist. Our retrospective cohort study aimed to investigate the mortality trends and disparities among patients with endometrial cancer in the USA. METHODS: Patients with endometrial cancer mortality from 1999 to 2020 were analyzed from the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER). Age-adjusted mortality rates (AAMRs) per 100,000 individuals were compared across different races and geographical regions. RESULTS: From 1999 to 2020, endometrial cancer accounted for 90,145 deaths in the USA. Overall, the AAMRs of endometrial cancer increased significantly from 2.50 (95% CI, 2.41-2.58) in 1999 to 3.94 (95% CI, 3.85-4.04) per 100,000 individuals in 2020, with an AAPC of +2.23 (95% CI, 1.39-3.07). The highest AAMR was observed among African Americans (2.69 [95% CI, 2.65-2.74]), followed by whites (1.44 [95% CI, 1.43-1.45]), Hispanics (1.16 [95% CI, 1.13-1.20]), Asians (1.00 [95% CI, 0.96-1.04]), and American Indians (0.99 [95% CI, 0.88-1.10]). The highest AAMR from endometrial cancer was recorded in the Northeast region (1.73 [95% CI, 1.71-1.76]). CONCLUSION: There was an increasing trend of mortality rates from endometrial cancer in the last 2 decades, which disproportionately affected African Americans. Targeted interventions are warranted to address the mortality disparities among patients with endometrial cancer.

The Effect of Exercise on Cardiotoxicity in Women with Breast Cancer Receiving Anthracycline-Based Chemotherapy: A Systematic Review and Meta-Analysis.

INTRODUCTION: Breast cancer is the most common cancer in women with a 5-year survival over 90%. However, anthracycline-based chemotherapy causes significant cardiotoxicity often requiring discontinuation of chemotherapeutic regimen among breast cancer survivors. We conducted a systematic review and meta-analysis to evaluate the efficacy of exercise training in mitigating anthracycline-related cardiotoxicity among women with breast cancer. METHODS: We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus databases. The outcomes of interest were left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), early to atrial filling velocity (E/A) ratio, maximal oxygen consumption (VO2 max), and cardiac output (CO). We used the Cochrane risk-of-bias tool for randomized trials (RoB 2) to assess the risk of bias in individual studies. RESULTS: We identified a total of 596 articles with 5 trials included in the final analysis. Exercise training was associated with an increase in VO2 max compared with no exercise training (mean difference, 3.95 [95% CI, 0.63-7.26]; I2 = 99.68%). Other cardiovascular outcomes such as LVEF (mean difference, 1.76 [95% CI, -1.95 to 5.46]; I2 = 99.44%), GLS (mean difference, 0.30 [95% CI, -0.49 to 1.10]; I2 = 96.63%), E/A ratio (mean difference, 0.05 [95% CI, -0.05 to 0.15]; I2 = 94.16%), and CO (mean difference, 0.38 [95% CI, -0.91 to 1.66]; I2 = 99.73%) are similar between patients who underwent exercise training and those who did not. CONCLUSIONS: Exercise was associated with an improvement in maximal oxygen uptake among women with breast cancer receiving anthracycline-based chemotherapy.

Reducing racial and ethnic disparities in cardiovascular outcomes among cancer survivors.

PURPOSE OF REVIEW: Analyze current evidence on racial/ethnic disparities in cardiovascular outcomes among cancer survivors, identifying factors and proposing measures to address health inequities. RECENT FINDINGS: Existing literature indicates that the Black population experiences worse cardiovascular outcomes following the diagnosis of both initial primary cancer and second primary cancer, with a notably higher prevalence of cardio-toxic events, particularly among breast cancer survivors. Contributing socioeconomic factors to these disparities include unfavorable social determinants of health, inadequate insurance coverage, and structural racism within the healthcare system. Additionally, proinflammatory epigenetic modification is hypothesized to be a contributing genetic variation factor. Addressing these disparities requires a multiperspective approach, encompassing efforts to address racial disparities and social determinants of health within the healthcare system, refine healthcare policies and access, and integrate historically stigmatized racial groups into clinical research. Racial and ethnic disparities persist in cardiovascular outcomes among cancer survivors, driven by multifactorial causes, predominantly associated with social determinants of health. Addressing these healthcare inequities is imperative, and timely efforts must be implemented to narrow the existing gap effectively.

Lappaol F regulates the cell cycle by activating CDKN1C/p57 in human colorectal cancer cells.

CONTEXT: Lappaol F (LAF), a natural lignan from Arctium lappa Linné (Asteraceae), inhibits tumor cell growth in vitro and in vivo. The underlying mechanism involves the suppression of the Yes-associated protein. However, the specific role of LAF in cell cycle regulation remains unknown. OBJECTIVE: This study determined the molecular mechanism by which LAF regulates cell cycle progression. MATERIALS AND METHODS: Various colon cancer cell lines (SW480, HCT15, and HCT116) were treated with LAF (25, 50, and 75 µmol/L) for 48 h. The effects of LAF on cell proliferation and cell cycle were determined using sulforhodamine B and flow cytometry assays. Differentially expressed proteins (DEPs) were identified using quantitative proteomics. Bioinformatic analysis of DEPs was conducted via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Expression levels of DEPs in the cell cycle pathway were analyzed using RT-qPCR and western blotting. RESULTS: LAF suppressed the proliferation of SW480, HCT15, and HCT116 cells (IC50 47.1, 51.4, and 32.8 µmol/L, respectively) and induced cell cycle arrest at the S phase. A total of 6331 proteins were identified and quantified, of which 127 were differentially expressed between the LAF-treated and untreated groups. GO and KEGG enrichment analyses revealed that DEPs mainly participated in the cell cycle. CDKN1C/p57 showed the most significant differential expression, with the highest fold-change (3.155-fold). Knockdown of CDKN1C/p57 attenuated the S phase cell cycle arrest and proliferation inhibition induced by LAF. CONCLUSION: LAF exerts antitumor effects via S phase arrest by activating CDKN1C/p57 in colorectal cancer cells.

Formicincola oecophyllae gen. nov. sp. nov., a novel member of the family Acetobacteraceae isolated from the weaver ant Oecophylla smaragdina.

In this study, a novel bacterium designated F3b2T was isolated from the gut sample of weaver ant Oecophylla smaragdina and characterised. Strain F3b2T was a Gram-negative, aerobic, non-motile, ovoid-shaped bacterium and grows optimally at 28-30 °C. Its major respiratory quinone is ubiquinone 10 (Q-10) and the major fatty acids are C18:1 ω7c, C19:0 cyclo ω8c and C16:0, representing 85% of the total fatty acids. The 16S rRNA gene sequence of strain F3b2T was highest in similarity to that of Oecophyllibacter saccharovorans DSM106907T and Swingsia samuieinsis NBRC 107927T at 94.35% and 91.96%, respectively. A 16S rRNA gene-based phylogenetic analysis and a core genes-based phylogenomic analysis placed strain F3b2T in a distinct lineage in the family Acetobacteraceae. The phylogenetic placement was supported by lower than species delineation threshold average nucleotide identity (ANI) (≤ 70.2%), in silico DNA-DNA hybridization (DDH) (≤ 39.5%) and average amino acid identity (AAI) (≤ 63.5%) values between strain F3b2T and closest neighbours. These overall genome relatedness indices also supported the assignment of strain F3b2T to a novel genus within Acetobacteraceae. The genome of strain F3b2T was 1.96 Mb with 60.4% G + C DNA content. Based on these results, strain F3b2T represented a novel taxon of Acetobacteraceae, for which we proposed the name Formicincola oecophyllae gen. nov. sp. nov., and strain F3b2T (= LMG 30590T = DSM 106908T = NBRC 113640T = KCTC 62951T) as the type strain.

A Cross-Sectional Evaluation of Complementary and Alternative Medicine Use in a Non-urban Malaysian Population.

Complementary and alternative medicine (CAM) therapies have been an integral part of Malaysia culture for many centuries. In recent years influences from other parts of the world have gained a foot-hold in Malaysian popular culture. We investigated the engagement with CAM in a non-urban, Malaysian population. We investigated the association of CAM use with cultural influence, perceived health status, gender and age. We recruited 700 adult participants to this study across three sites in central Malaysia. We found massage, Vitamin supplements, Herbal medicine and traditional Chinese medicine to be the most popular CAM modalities with participation at 67.7%, 55.7%, 55.5% and 26.3% respectively. CAM use was equally high at 67% among those people who claimed a predominantly Malay or Chinese cultural influence. The use of vitamins and participation in yoga were at higher prevalence among female participants compared to males. There was no gender difference for other CAM modalities. There were differences between age groups for most CAM modalities, and those over 50 years tended to be the highest frequency users for most modalities. There is a high rate of CAM use in non-urban Malaysia with younger people being more engaged with less traditional modalities such as aromatherapy, yoga and music therapy.

Impact of sense of coherence, resilience and loneliness on quality of life amongst older adults in long-term care: A correlational study using the salutogenic model.

AIMS: This study aimed to identify the predicting factors of quality of life (QoL) from a set of psychosocial, sociodemographic and clinical variables amongst older adults in a long-term care setting. DESIGN: A cross-sectional, descriptive correlational study. METHOD: The study was conducted in a nursing home and a day care centre from July to December 2019. Two hundred older adults were recruited. Guided by the salutogenic model, the sense of coherence (SOC) scale, Connor-Davidson resilience scale, de Jong Gierveld loneliness scale and World Health Organization quality of life instrument-older adults (WHOQOL-OLD) were used. The sociodemographic and clinical profiles of participants were collected. Descriptive statistics, Pearson product-moment correlation coefficient, independent-samples t test, one-way analysis of variance and stepwise regression were utilised in the analysis. RESULTS: The mean score for WHOQOL-OLD was 94.42 ± 19.55. The highest mean score was observed in the "Death and Dying" facet, while the lowest mean scores were reflected in the "Autonomy" and "Intimacy" facets of QoL. Regardless of resident type, most QoL scores were similar across different variables. Based on the stepwise regression, higher manageability and meaningfulness in SOC, higher resilience, lower social loneliness, lower emotional loneliness and hearing impairments are significantly associated with higher QoL. CONCLUSION: Manageability, meaningfulness and resilience should be enhanced while ameliorating feelings of loneliness to improve the QoL amongst older adults receiving long-term care. Age, marital status, educational level, care arrangement, body mass index, performance in activities of daily living, comorbidities and hearing and mobility impairments could influence QoL and thus warrant more attention. IMPACT: Future interventions can be conducted in group sessions to facilitate social interaction and alleviate loneliness. More resources should be allocated to enhance older adults' care arrangements and coping mechanisms to provide them with the support, as they face challenges in daily life due to mobility impairment and other restrictions.

Lappaol F, an anticancer agent, inhibits YAP via transcriptional and post-translational regulation.

CONTEXT: Lappaol F (LAF), a natural lignan from Arctium lappa Linné (Asteraceae), inhibits tumour cell growth by inducing cell cycle arrest. However, its underlying anticancer mechanism remains unclear. OBJECTIVE: The effects of LAF on the Hippo-Yes-associated protein (YAP) signalling pathway, which plays an important role in cancer progression, were explored in this study. MATERIALS AND METHODS: Cervical (HeLa), colorectal (SW480), breast (MDA-MB-231) and prostate (PC3) cancer cell lines were treated with LAF at different concentrations and different durations. BALB/c nude mice bearing colon xenografts were intravenously injected with vehicle, LAF (10 or 20 mg/kg) or paclitaxel (10 mg/kg) for 15 days. The expression and nuclear localisation of YAP were analysed using transcriptome sequencing, quantitative PCR, western blotting and immunofluorescence. RESULTS: LAF suppressed the proliferation of HeLa, MDA-MB-231, SW480 and PC3 cells (IC50 values of 41.5, 26.0, 45.3 and 42.9 µmol/L, respectively, at 72 h), and this was accompanied by significant downregulation in the expression of YAP and its downstream target genes at both the mRNA and protein levels. The expression of 14-3-3σ, a protein that causes YAP cytoplasmic retention and degradation, was remarkably increased, resulting in a decrease in YAP nuclear localisation. Knockdown of 14-3-3σ with small interfering RNA partially blocked LAF-induced YAP inhibition and anti-proliferation effects. In colon xenografts, treatment with LAF led to reduced YAP expression, increased tumour cell apoptosis and tumour growth inhibition. CONCLUSION: LAF was shown to be an inhibitor of YAP. It exerts anticancer activity by inhibiting YAP at the transcriptional and post-translational levels.

Planococcus versutus sp. nov., isolated from soil.

A taxonomic study was performed on a novel Gram-stain-positive, coccus-shaped, orange-pigmented motile bacterium, designated as strain L10.15T. The organism was isolated from a soil sample collected in Lagoon Island (close to Adelaide Island, western Antarctic Peninsula) using a quorum-quenching enrichment medium. Growth occurred at 4-30 °C, pH 6-11 and at moderately high salinity (0-15 %, w/v, NaCl), with optimal growth at 26 °C, at pH 7-8 and with 6 % (w/v) NaCl. 16S rRNA gene sequence analysis showed that strain L10.15T belonged to the genus Planococcus and was closely related to Planococcus halocryophilus Or1T (99.3 % similarity), Planococcus donghaensis JH1T (99.0 %), Planococcus antarcticus DSM 14505T (98.3 %), Planococcus plakortidis AS/ASP6 (II)T (97.6 %), Planococcus maritimus TF-9T (97.5 %), Planococcus salinarum ISL-6T (97.5 %) and Planococcus kocurii NCIMB 629T (97.5 %). However, the average nucleotide identity-MUMmer analysis showed low genomic relatedness values of 71.1-81.7 % to the type strains of these closely related species of the genus Planococcus. The principal fatty acids were anteiso-C15 : 0, C16 : 1ω7c and anteiso-C17 :  0, and the major menaquinones of strain L10.15T were MK-5 (48 %), MK-6 (6 %) and MK-7 (44 %). Polar lipid analysis revealed the presence of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and aminophospholipid. The DNA G+C content was 39.4 mol%. The phenotypic and genotypic data indicate that strain L10.15T represents a novel species of the genus Planococcus, for which the name Planococcus versutus sp. nov. is proposed. The type strain is L10.15T (=DSM 101994T=KACC 18918T).

Quorum sensing activity of Hafnia alvei isolated from packed food.

Quorum sensing (QS) is a mechanism adopted by bacteria to regulate expression of genes according to population density. N-acylhomoserine lactones (AHLs) are a type of QS signalling molecules commonly found in Gram-negative bacteria which have been reported to play a role in microbial spoilage of foods and pathogenesis. In this study, we isolated an AHL-producing Hafnia alvei strain (FB1) from spherical fish pastes. Analysis via high resolution triple quadrupole liquid chromatography/mass spectrometry (LC/MS) on extracts from the spent supernatant of H. alvei FB1 revealed the existence of two short chain AHLs: N-(3-oxohexanoyl) homoserine lactone (3-oxo-C6-HSL) and N-(3-oxo- octanoyl) homoserine lactone (3-oxo-C8-HSL). To our knowledge, this is the first report of the production of AHLs, especially 3-oxo-C8-HSL, by H. alvei.

Causes of Death and Mortality Trends in Individuals with Thalassemia in the United States, 1999-2020.

Purpose: Our study aims to describe the mortality trends and disparities among individuals with thalassemia in the United States (US). Patients and Methods: We used CDC WONDER database to calculate the age-adjusted mortality rates (AAMRs) per 1,000,000 individuals and used the Joinpoint Regression Program to measure the average annual percent change (AAPC). Subgroup evaluations were performed by sex, age, race, census region, and urbanization level. Results: From 1999 to 2020, there were 2797 deaths relatd to thalassemia in the US. The AAMR of thalassemia-related death showed a decreasing trend from 0.50 (95% CI, 0.41-0.58) in 1999 to 0.48 (95% CI, 0.41-0.55) in 2020 with the AAPC of -1.42 (95% CI, -2.42, -0.42). Asians have the highest AAMR (1.34 [95% CI, 1.20-1.47]), followed by non-Hispanic Blacks (0.65 [95% CI, 0.59-0.71]), non-Hispanic Whites (0.32 [95% CI, 0.30-0.33]), and Hispanics (0.11 [95% CI, 0.08-0.14]). Cardiovascular disease remains the leading cause of death among individuals with thalassemia. The urban population has a higher AAMR than the rural population (0.43 [95% CI, 0.41-0.45] vs 0.29 [95% CI, 0.26-0.32]). Conclusion: Our study calls for targeted interventions to address the racial and geographic disparities existed among individuals of thalassemia in the US.

Non-Hodgkin lymphoma mortality disparities across different sexes, races, and geographic locations.

Non-Hodgkin lymphoma (NHL) is one of the most common hematological cancers in the United States. The mortality rate of NHL in the United States is the sixth highest among all cancers. Our cross-sectional study aims to examine the trends and disparity in NHL mortality. We analyzed death certificate data from the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) United States to determine the NHL mortality trends among the U.S. population aged ≥15 years. NHL (ICD-10 C82-85) was listed as the underlying cause of death. Age-adjusted mortality rates (AAMRs) per 100,000 individuals and joinpoint trend analysis were performed to determine the average annual percent change (AAPC) in AAMR trends. From 1999 to 2020, NHL accounted for 457,143 deaths in the United States, of which 54% are men and 46% are women. The NHL AAMR decreased significantly from 10.59 to 6.21 per 100,000 individuals with an AAPC of -2.55. Men had a higher AAMR than women (10.10 vs 6.29 per 100,000 individuals). Whites recorded the highest AAMR (8.43 per 100,000 individuals), followed by Hispanics (6.32 per 100,000 individuals), Blacks (5.71 per 100,000 individuals), American Indians (5.31 per 100,000 individuals), and Asians (5.10 per 100,000 individuals). Those who lived in the Midwest and the rural areas had the highest AAMR at 8.60 and 8.35 per 100,000 individuals respectively. Despite the declining NHL mortality rate, this study calls for targeted intervention to improve outcomes for susceptible individuals affected by NHL.

Pancreatic cancer mortality trends in the United States: how much have we moved the needle?

Background: Despite advances made in pancreatic cancer treatment, the extent of progress made in pancreatic cancer mortality at the population level remains unclear. Our cross-sectional study sought to measure trends in pancreatic cancer mortality in the United States in the last 2 decades. Methods: Patients with pancreatic cancer mortality from 1999 to 2020 were analyzed from the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER). Age-adjusted mortality rates (AAMRs) per 100,000 individuals were measured. We used joinpoint trend analysis to determine average annual percent change (AAPC) in AAMR trends. Results: From 1999 to 2020, pancreatic cancer accounted for 809,197 deaths. Overall, the AAMRs of pancreatic cancer increased from 20.74 per 100,000 individuals in 1999 to 21.60 per 100,000 individuals in 2020. The highest AAMR was recorded in non-Hispanic Black males (30.11 per 100,000 individuals), and the lowest, in non-Hispanic White females (18.51 per 100,000 individuals). Patients aged 75-84 years had the highest AAMR (6.87 per 100,000 individuals) compared to the younger patients. The highest AAMR was observed in the Northeast region (22.07 per 100,000 individuals) and rural regions (21.29 per 100,000 individuals). Conclusions: There was no improvement in pancreatic cancer mortality in the last two decades. These findings emphasize the importance of efforts to increase access to multidisciplinary cancer care with the realization that without it, improvements in treatment standards will not translate to lower cancer mortality at the population level.

Social Vulnerability and Sickle Cell Disease Mortality in the US.

Importance: Social determinants of health (SDOH) influence health outcomes, including those of sickle cell disease (SCD), despite advancements in treatments like disease-modifying therapies. Objective: To investigate the association of SDOH with SCD mortality rates from 2016 to 2020. Design, Setting, and Participants: This cross-sectional study combined county-level data from the Centers for Disease Control and Prevention and Agency for Toxic Substances and Disease Registry Social Vulnerability Index (SVI) with SCD mortality data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database from January 1, 2016, to December 31, 2020. US counties were divided into 4 quartile (Q) models according to their SVI scores. Deaths from SCD in the US among patients of all ages were included. Data analysis occurred from March to April 2024. Exposure: SVI score. Main Outcomes and Measures: Age-adjusted mortality rates (AAMRs) per 1 000 000 individuals were measured. Rate ratios (RRs) were obtained by comparing county-specific AAMRs of SVI-Q4 with SVI-Q1. Results: From 2016 to 2020, among a total population of 1 633 737 771 individuals, there were 2635 deaths from SCD (1289 male [49.1%] and 1336 female [50.9%]). There were 1480 deaths in Q4, 687 deaths in Q3, 344 deaths in Q2, and 114 deaths in Q1. Higher SVI was associated with 2.11 excess deaths per 1 000 000 individuals (RR, 4.90; 95% CI, 4.81-5.00). Similar trends were seen for both males (RR, 4.56; 95% CI, 4.44-4.69) and females (RR, 5.85; 95% CI, 5.68-6.03). Middle-aged patients with SCD had the highest mortality rate in Q4, with 3.45 excess deaths per 1 000 000 individuals (RR, 4.97; 95% CI, 4.85-5.09). Higher SVI was associated with 2.29 excess deaths per 1 000 000 individuals in African American individuals with SCD (RR, 1.24; 95% CI, 1.22-1.27]). In White individuals with SCD, higher SVI was associated with 0.12 excess deaths per 1 000 000 individuals (RR not available due to unreliable data in Q1). When stratifying by census region, the highest level of SCD-related mortality was in the Northeast, with higher SVI associated with 3.16 excess deaths per 1 000 000 individuals (RR, 8.02; 95% CI, 7.66-8.40). Conclusions: In this cross-sectional study of the association of SVI with SCD mortality rates, higher SVI was associated with higher SCD mortality across US counties. These findings underscore the importance of addressing social determinants of health to improve mortality outcomes among patients with SCD.

Virus Propagation and Cell-Based Colorimetric Quantification.

Zika virus (ZIKV) is a mosquito-borne virus belonging to the genus Flavivirus. ZIKV infection has been associated with congenital brain abnormalities and potentially Guillain-Barré syndrome in adults. Research on ZIKV to understand the disease mechanisms is important to facilitate vaccine and treatment development. The method of quantifying viruses is crucial and fundamental in the field of virology. The focus forming assay (FFA) is a virus quantification assay that detects the viral antigen with antibodies and identifies the infection foci of cells using the peroxidase immunostaining technique. The current study describes the virus propagation and quantification protocol using both 24-well and 96-well (high throughput) formats. Compared with other similar studies, this protocol has further described foci size optimization, which can serve as a guide to expand the use of this assay for other viruses. Firstly, ZIKV propagation is performed in Vero cells for 3 days. The culture supernatant containing ZIKV is harvested and quantitated using the FFA. Briefly, the virus culture is inoculated onto Vero cells and incubated for 2-3 days. Foci formation is then determined after optimized staining processes, including cell fixation, permeabilization, blocking, antibody binding, and incubation with peroxidase substrate. The stained virus foci are visualized using a stereo microscope (manual counting in 24-well format) or software analyzer (automated counting in 96-well format). The FFA provides reproducible, relatively fast results (3-4 days) and is suitable to be used for different viruses, including non-plaque-forming viruses. Subsequently, this protocol is useful for the study of ZIKV infection and could be used to detect other clinically important viruses.

SARS-CoV-2 genomic surveillance in Malaysia: displacement of B.1.617.2 with AY lineages as the dominant Delta variants and the introduction of Omicron during the fourth epidemic wave.

OBJECTIVES: This study reported SARS-CoV-2 whole genome sequencing results from June 2021 to January 2022 from seven genome sequencing centers in Malaysia as part of the national surveillance program. METHODS: COVID-19 samples that tested positive by reverse transcription polymerase chain reaction and with cycle threshold values <30 were obtained throughout Malaysia. Sequencing of SARS-CoV-2 complete genomes was performed using Illumina, Oxford Nanopore, or Ion Torrent platforms. A total of 6163 SARS-CoV-2 complete genome sequences were generated over the surveillance period. All sequences were submitted to the Global Initiative on Sharing All Influenza Data database. RESULTS: From June 2021 to January 2022, Malaysia experienced the fourth wave of COVID-19 dominated by the Delta variant of concern, including the original B.1.617.2 lineage and descendant AY lineages. The B.1.617.2 lineage was identified as the early dominant circulating strain throughout the country but over time, was displaced by AY.59 and AY.79 lineages in Peninsular (west) Malaysia, and the AY.23 lineage in east Malaysia. In December 2021, pilgrims returning from Saudi Arabia facilitated the introduction and spread of the BA.1 lineage (Omicron variant of concern) in the country. CONCLUSION: The changing trends of circulating SARS-CoV-2 lineages were identified, with differences observed between west and east Malaysia. This initiative highlighted the importance of leveraging research expertise in the country to facilitate pandemic response and preparedness.

Emergence of B.1.524(G) SARS-CoV-2 in Malaysia during the third COVID-19 epidemic wave.

The COVID-19 pandemic first emerged in Malaysia in Jan 2020. As of 12th Sept 2021, 1,979,698 COVID-19 cases that occurred over three major epidemic waves were confirmed. The virus contributing to the three epidemic waves has not been well-studied. We sequenced the genome of 22 SARS-CoV-2 strains detected in Malaysia during the second and the ongoing third wave of the COVID-19 epidemic. Detailed phylogenetic and genetic variation analyses of the SARS-CoV-2 isolate genomes were performed using these newly determined sequences and all other available sequences. Results from the analyses suggested multiple independent introductions of SARS-CoV-2 into Malaysia. A new B.1.524(G) lineage with S-D614G mutation was detected in Sabah, East Malaysia and Selangor, Peninsular Malaysia on 7th October 2020 and 14th October 2020, respectively. This new B.1.524(G) group was not the direct descendant of any of the previously detected lineages. The new B.1.524(G) carried a set of genetic variations, including A701V (position variant frequency = 0.0007) in Spike protein and a novel G114T mutation at the 5'UTR. The biological importance of the specific mutations remained unknown. The sequential appearance of the mutations, however, suggests that the spread of the new B.1.524(G) lineages likely begun in Sabah and then spread to Selangor. The findings presented here support the importance of SARS-CoV-2 full genome sequencing as a tool to establish an epidemiological link between cases or clusters of COVID-19 worldwide.