Advances towards genome-based acute myeloid leukemia classification: A comparative analysis of WHO-HAEM4R, WHO-HAEM5, and International Consensus Classification.

Two recent guidelines, the 5th edition of the World Health Organization Classification of Haematolymphoid Tumours (WHO-HAEM5) and the International Consensus Classification (ICC), were published to refine the diagnostic criteria of acute myeloid leukemia (AML). They both consider genomic features more extensively and expand molecularly defined AML subtypes. In this study, we compared the classifications of 1135 AML cases under both criteria. According to WHO-HAEM5 and ICC, the integration of whole transcriptome sequencing, targeted gene mutation screening, and conventional cytogenetic analysis identified defining genetic abnormalities in 89% and 90% of AML patients, respectively. The classifications displayed discrepancies in 16% of AML cases after being classified using the two guidelines, respectively. Both new criteria significantly reduce the number of cases defined by morphology and differentiation. However, their clinical implementation heavily relies on comprehensive and sophisticated genomic analysis, including genome and transcriptome levels, alongside the assessment of pathogenetic somatic and germline variations. Discrepancies between WHO-HAEM5 and ICC, such as the assignment of RUNX1 mutations, the rationality of designating AML with mutated TP53 as a unique entity, and the scope of rare genetic fusions, along with the priority of concurrent AML-defining genetic abnormalities, are still pending questions requiring further research for more elucidated insights.

Exercise ameliorates fine particulate matter-induced metabolic damage through the SIRT1/AMPKα/PGC1-α/NRF1 signaling pathway.

Air pollution, particularly fine particulate matter (PM2.5), poses a major threat to human health. Exercise has long been recognized as a beneficial way to maintain physical health. However, there is limited research on whether exercise can mitigate the damage caused by PM2.5 exposure. In this study, the mice were exercised on the IITC treadmill for 1 h per day, then exposed to concentrated PM2.5 for 8 h. After 2, 4 and 6-month exercise and PM2.5 exposure, the glucose tolerance and insulin tolerance were determined. Meanwhile, the corresponding indicators in epididymal white adipose tissue (eWAT), brown adipose tissue (BAT) and skeletal muscle were detected. The results indicated that PM2.5 exposure significantly increased insulin resistance (IR), while exercise effectively attenuated this response. The observations of muscle, BAT and eWAT by transmission electron microscopy (TEM) showed that PM2.5 significantly reduced the number of mitochondria in all of the three tissues mentioned above, and decreased the mitochondrial area in skeletal muscle and BAT. Exercise reversed the changes in mitochondrial area in all of the three tissues, but had no effect on the reduction of mitochondrial number in skeletal muscle. At 2 months, the expressions of Mfn2, Mfn1, OPA1, Drp1 and Fis1 in eWAT of the PM mice showed no significant changes when compared with the corresponding FA mice. However, at 4 months and 6 months, the expression levels of these genes in PM mice were higher than those in the FA mice in skeletal muscle. Exercise intervention significantly reduced the upregulation of these genes induced by PM exposure. The study indicated that PM2.5 may impact mitochondrial biogenesis and dynamics by inhibiting the SIRT1/AMPKα/PGC1-α/NRF1 pathway, which further lead to IR, glucose and lipid disorders. However, exercise might alleviate the damages caused by PM2.5 exposure.

DNTT activation, TdT-aided gene length mutation, and better prognosis in ATG-based regimen allo-HSCT in AML.

This study aimed to investigate the relationship between anomalous DNA nucleotidylexotransferase (DNTT) activation and the mutagenesis of gene length mutations (LMs) in acute myeloid leukemia (AML), and the relevance of their prognosis in antithymocyte globulin (ATG)-based regimen allogeneic hematopoietic stem cell transplantation (allo-HSCT). A cohort of 578 AML cases was enrolled. Next-generation sequencing was performed to screen mutations of 86 leukemia driver genes. RNA-seq was used to analyze gene expression. Prognostic analysis was investigated in 239 AML cases who underwent ATG-based regimen allo-HSCT. We report a refined subtyping algorithm of LMs (type I-IV) based on sequence anatomy considering the TdT-aided mutagenesis mechanism. GC content adjacent to LM junctions, inserted nontemplate nucleotide bases, and DNTT expression analysis supported the DNTT activation and TdT-aided mutagenesis in type II/III LMs in the total AML cohort. Both single-variate and multivariate analyses showed a better overall survival of FLT3 type III compared to type I in a subset of ATG-based regimen allo-HSCT cases. The novel LM subtyping algorithm not only deciphers the etiology of the mutagenesis of LMs but also helps to fine-tune prognosis differentiation in AML. The possible prognostic versatility of this novel LM subtyping algorithm in terms of chemotherapy, targeted therapy, and allo-HSCT merits further investigation.

Impact of the COVID-19 Pandemic on Diabetes Care Among a North Carolina Patient Population.

In this study, researchers reviewed electronic health record data to assess whether the coronavirus disease 2019 pandemic was associated with disruptions in diabetes care processes of A1C testing, retinal screening, and nephropathy evaluation among patients receiving care with Wake Forest Baptist Health in North Carolina. Compared with the pre-pandemic period, they found an increase of 13-21 percentage points in the proportion of patients delaying diabetes care for each measure during the pandemic. Alarmingly, delays in A1C testing were greatest for individuals with the most severe disease and may portend an increase in diabetes complications.

Hepatitis B Virus Pregenomic RNA Reflecting Viral Replication in Distal Non-tumor Tissues as a Determinant of the Stemness and Recurrence of Hepatocellular Carcinoma.

Background: The existence of hepatic cancer stem cells (CSCs) contributes to chemotherapy resistance and cancer recurrence after treatment or surgery. However, very little is known about the hepatitis B virus (HBV) replication and its relationship with the stemness of hepatocellular carcinoma (HCC) in HBV-related HCC patients. Methods: We collected tumor tissues (T), matched adjacent non-tumor tissues (NT), and distal non-tumor tissues (FNT) from 55 HCC patients for analysis. Results: We found HBV DNA levels were higher in T samples than NT and FNT samples, but HBV pgRNA and total RNA expressed lower in T samples. HBV pgRNA and total RNA correlate to HBV DNA among the T, NT, and FNT samples. Further evidence for HBV replication in T samples was provided by HBV S, reverse transcriptase, and X genes sequencing, showing that HBV sequences and genotypes differed between T and matched NT and FNT samples. HBV pgRNA and total RNA showed more frequent significant correlations with CSC markers in NT samples in HBsAg-positive patients. The markers CD133 and OCT4 expressed higher in FNT samples, and HBV replication marker of pgRNA levels was significantly positively correlated to these two markers only in FNT samples. The detection of pgRNA and OCT4 in FNT was correlated to the recurrence of HCC in the resection of HCC patients. Analysis of HBV receptor, sodium taurocholate co-transporting polypeptide (NTCP), showed that NTCP was correlated negatively to CSC markers in T samples, except for the CD44. Conclusion: HBV replication may present in HCC with a weak transcriptomic signature. Moreover, the expression level of HBV pgRNA in distal non-tumor tissues is a sensitive marker for HBV replication and prognosis, which is associated with CSC-related markers especially with OCT4 in distal non-tumor tissues and recurrence of HCC in HBV-related HCC patients.

Ambient PM2.5-induced brain injury is associated with the activation of PI3K/AKT/FoxO1 pathway.

PM2.5-related neurological and mental diseases, such as cognitive impairment and stroke, tend to cause disability. Six-week-old male C57BL/6 mice were divided into 6 groups and exposed to concentrated PM2.5 or filtered air for 2, 4, and 6 months, respectively. The neurobehavioral changes of mice were tested. The weight of the whole brain and olfactory bulbs were recorded at the end of exposure, and the brain structure was observed by hematoxylin and eosin (HE) staining. Serum indicators, mRNA, and protein expressions were detected. The spatial learning memory ability was impaired, and the mice were more anxious after PM2.5 exposure. Relative brain weight decreased with age, and PM2.5 exposure exceeded the decrease of relative brain weight. Interestingly, superoxide dismutase (SOD) and albumin decreased in the PM2.5-exposed groups although neuronal morphology and other serum indicators did not show significant difference between PM and FA groups. Moreover, PM2.5 induced the increase of plasminogen at 2 months but recovered at 4 months and then increased at 6 months again. The results from protein expression and transcriptomic test demonstrated that PI3K/AKT/FoxO1 pathway might be activated after 6-month PM2.5 exposure in mice. Indicators albumin, the percentage of albumin over IgG (A/G value), and plasminogen were the main serous changes in mice after early-stage (2 months) and long-term (6 months) PM2.5 exposure. In addition, early-stage injury induced by PM2.5 might recover at later time point and display significant injury again with the exposure time. PM2.5 exposure-induced brain injury might be associated with the activation of PI3K/AKT/FoxO1 pathway.

Examination of Elective Bariatric Surgery Rates Before and After US Affordable Care Act Medicaid Expansion.

Importance: There is limited evidence on whether the Affordable Care Act Medicaid expansion beginning in 2014 improved access to elective procedures. Uninsured individuals are at higher risk of obesity and may have experienced improved uptake of bariatric surgery following Medicaid expansion. Objective: To examine the association between Medicaid expansion and the receipt of inpatient elective bariatric surgery among Medicaid-covered and uninsured individuals aged 26 to 64 years. Design Setting and Participants: This cohort study used difference-in-differences analysis of all-payer data (2010-2017) of 637 557 elective bariatric surgeries for patients aged 26 to 74 years from 11 Medicaid expansion states and 6 nonexpansion states. Nonexpansion states and individuals aged 65 to 74 years were control cohorts. Data analysis was performed from July 6, 2020, to July 23, 2021. Exposure: Living in a Medicaid expansion state. Main Outcomes and Measures: The main outcomes were the (1) number of elective bariatric surgeries, (2) population count, and (3) rate of bariatric surgery (number of surgeries per 10 000 population) among Medicaid-covered and uninsured individuals. Results: Of the 600 798 elective bariatric surgeries in adults aged 26 to 64 years between 2010 and 2017 from the 17 study states, Medicaid-covered and uninsured individuals accounted for 18.3% of the total surgery volume in expansion states and 14.5% in nonexpansion states. A total of 296 798 patients (78.9%) in expansion states were women vs 177 386 (78.9%) in nonexpansion states. Among individuals aged 26 to 64 years, the median age was 44 (IQR, 37-52) years. Racial and ethnic distribution was non-Hispanic White, 60.2%; non-Hispanic Black, 17.7%; Hispanic, 16.6%; and other, 5.5%. Between 2013 and 2017, the volume of bariatric surgeries for Medicaid-covered and uninsured patients increased annually by 30.3% in expansion states and 16.5% in nonexpansion states. Medicaid expansion was associated with a 36.6% annual increase (95% CI, 8.2% to 72.5%) in surgery volume, a 9.0% annual increase (95% CI, 3.8% to 14.5%) in the population, and a 25.5% change (95% CI, -1.3% to 59.4%) in the rate of bariatric surgery. By race and ethnicity, Medicaid expansion was associated with an increase in the rate of bariatric surgery among non-Hispanic White individuals (31.6%; 95% CI, 6.1% to 63.0%) but no significant change among non-Hispanic Black (5.9%; 95% CI, -19.8% to 39.9%) and Hispanic (28.9%; 95% CI, -24.4% to 119.8%) individuals. Conclusions and Relevance: This cohort study found that Medicaid expansion was associated with increased rates of bariatric surgery among lower-income non-Hispanic White individuals, but not among Hispanic and non-Hispanic Black individuals.

Reduction of the occurrence of occult HBV infection in infants by increasing the dose of hepatitis B vaccine: a large prospective cohort study.

Occult hepatitis B virus (HBV) infection (OBI) has been observed among infants born to hepatitis B surface antigen (HBsAg)-positive mothers despite successful immunoprophylaxis. This study enrolled 549 infants [349 infants received a 10µg/dose of hepatitis B vaccine (HepB), and 200 infants received 20µg/dose HepB] born to HBsAg-positive mothers with HBV DNA load >6log10IU/mL. The anti-HBs levels in the 10µg group were significantly lower than that in the 20µg group both at 7 [652.48 (564.05-754.82) vs. 1541.72 (1268.69-1873.51) mIU/mL, P<0.001] and 12 months old [257.44 (220.29-300.88) vs. 1073.41 (839.27-1372.78) mIU/mL, P<0.001]. The OBI incidence in the 10µg group was significantly higher than that in the 20µg group at both 7 [21.55% (25/116) vs. 7.56% (9/119), P=0.002] and 12 months old [17.07% (14/82) vs. 6.90% (6/87), P=0.041]. OBI incidence in infants with anti-HBs levels <100mIU/mL was higher than that of those with anti-HBs ≥100mIU/mL [35.71% (5/14) vs. 13.12% (29/221), P=0.036]. This study showed that increasing the immunisation dose from 10µg to 20µg significantly improved anti-HBs levels and decreased OBI incidence in infants with a high maternal viral load. We recommend 20µg HepB to treat this high-risk population.

Quasispecies characteristic in "a" determinant region is a potential predictor for the risk of immunoprophylaxis failure of mother-to-child-transmission of sub-genotype C2 hepatitis B virus: a prospective nested case-control study.

OBJECTIVE: This study was performed to explore the correlation between the characteristics of hepatitis B virus (HBV) quasispecies in HBV-infected pregnant women and the risk of immunoprophylaxis failure for their infants. DESIGN: In this prospective nested case-control study, the characteristics of HBV quasispecies in mothers whose infants were immunoprophylaxis success (control group) and those whose infants were immunoprophylaxis failure (case group) were analysed by the clone-based sequencing of full-length HBV genome and next-generation sequencing (NGS) of "a" determinant region, and were compared between the two groups. RESULTS: The quasispecies characteristics including mutant frequency, Shannon entropy and mean genetic distance at amino acid level of "a" determinant region were significantly lower in case group than that in control group, using the full-length HBV genome clone-based sequencing assay. These results were confirmed by NGS assay. Notably, we discovered that the differences were also significant at nucleotide level by NGS assay. Furthermore, the risk of immunoprophylaxis failure could be predicted by analysing the three HBV quasispecies characteristics either at nucleotide level or at amino acid level of "a" determinant region, and the corresponding predictive values were tentatively set up. CONCLUSIONS: HBV quasispecies with a more complex mutant spectrum in "a" determinant region might be more vulnerable to extinct through mother-to-child-transmission (MTCT). More importantly, analysing HBV quasispecies characteristics in pregnant women with high HBV DNA load might be helpful to predict the high-risk population of immunoprophylaxis failure, and consequently provide accurate intervention against MTCT of HBV.

Characteristic Assessment of Diesel-degrading Bacteria Immobilized on Natural Organic Carriers in Marine Environment: the Degradation Activity and Nutrient.

Oil spill has led to severe environmental and ecological problems. Due to the harsh environmental conditions, the bioremediation technology is not successfully used to remedy the oil spill in marine environment. In this study, immobilization technology was used to immobilize bacteria on natural organic carriers (i.e., wood chips and maize straw). The higher surface area of in wood chips leads to larger biomass density (0.0242 gVSS/g) than that of maize straw of 0.0097 gVSS/g carrier. Compared with biodegradation efficiency of free bacteria (44.79%), the immobilized bacteria on wood chips and maize straw reached to 73.39% and 52.28%, respectively. The high biological activity of the immobilized bacteria can be also explained by nutrients, such as TN (total nitrogen) and TP (total phosphorus), released from wood chips and maize straw, which was 8.83 mg/g and 5.53 mg/g, 0.0624 mg/g and 0.0099 mg/g, respectively.

Characteristics of traditional Chinese medicine syndromes in post-stroke depression.

OBJECTIVE: To explore the main characteristics of syndromes in traditional Chinese medicine (TCM) in post-stroke depression (PSD) and to provide basis for treatments with TCM herbs. METHODS: According to diagnostic criteria of PSD, stroke patients and depression patients from Department of Neurology, First Affiliated Hospital, Anhui University of Traditional Chinese Medicine were assigned into cerebral stroke group (150 cases), depression group (151 cases) and PSD group (123 cases). Neuropsychological assessments and imaging and biochemical analyses were conducted. TCM syndrome differentiation for these diseases was performed. We also determined the characteristics of TCM syndromes of PSD, relative risk of the syndromes and their correlations with ages as well. RESULTS: Scores of qi stagnation and blood stasis, liver qi depression, and transformation of fire due to qi stagnation in PSD group were significant higher than those in cerebral stroke group (P<0.05, P<0.01). In cerebral stroke group, majority of the patients displayed one syndrome, while in PSD and depression groups, the patients had three or more syndromes. Of these syndromes, the incidence rate of syndrome of liver qi depression complicated with transformation of fire due to qi stagnation or flaring of fire due to yin deficiency was high. The syndrome of liver qi depression occurred much more frequently in PSD group and depression group than in cerebral stroke group (P<0.05, P<0.01). The logistic regression analysis showed that the syndrome of qi stagnation and blood stasis had high relative risk to PSD. The syndrome of deficiency of heart and spleen was positively correlated with age in cerebral stroke group. CONCLUSION: The main TCM syndromes of PSD and depression are qi stagnation and blood stasis, liver qi depression, and transformation of fire due to qi stagnation. The syndrome of deficiency of heart and spleen is closely related to age among the stroke patients. The syndrome of qi stagnation and blood stasis serves as an independent risk factor for PSD. The more complicated the syndromes are, the more serious depression becomes.