Acetylcytidine modification of Amotl1 by N-acetyltransferase 10 contributes to cardiac fibrotic expansion in mice after myocardial infarction.

Cardiac fibrosis is a pathological scarring process that impairs cardiac function. N-acetyltransferase 10 (Nat10) is recently identified as the key enzyme for the N4-acetylcytidine (ac4C) modification of mRNAs. In this study, we investigated the role of Nat10 in cardiac fibrosis following myocardial infarction (MI) and the related mechanisms. MI was induced in mice by ligation of the left anterior descending coronary artery; cardiac function was assessed with echocardiography. We showed that both the mRNA and protein expression levels of Nat10 were significantly increased in the infarct zone and border zone 4 weeks post-MI, and the expression of Nat10 in cardiac fibroblasts was significantly higher compared with that in cardiomyocytes after MI. Fibroblast-specific overexpression of Nat10 promoted collagen deposition and induced cardiac systolic dysfunction post-MI in mice. Conversely, fibroblast-specific knockout of Nat10 markedly relieved cardiac function impairment and extracellular matrix remodeling following MI. We then conducted ac4C-RNA binding protein immunoprecipitation-sequencing (RIP-seq) in cardiac fibroblasts transfected with Nat10 siRNA, and revealed that angiomotin-like 1 (Amotl1), an upstream regulator of the Hippo signaling pathway, was the target gene of Nat10. We demonstrated that Nat10-mediated ac4C modification of Amotl1 increased its mRNA stability and translation in neonatal cardiac fibroblasts, thereby increasing the interaction of Amotl1 with yes-associated protein 1 (Yap) and facilitating Yap translocation into the nucleus. Intriguingly, silencing of Amotl1 or Yap, as well as treatment with verteporfin, a selective and potent Yap inhibitor, attenuated the Nat10 overexpression-induced proliferation of cardiac fibroblasts and prevented their differentiation into myofibroblasts in vitro. In conclusion, this study highlights Nat10 as a crucial regulator of myocardial fibrosis following MI injury through ac4C modification of upstream activators within the Hippo/Yap signaling pathway.

Synergistic Interaction of Ionic Liquid Grafted Poly(vinylidene Fluoride) and Carbon Nanotubes to Construct Water Treatment Membranes with Multiple Separation Properties.

In this study, the dual strategy of 1-butyl-3-vinylimidazolium bromide ionic liquid (IL) grafting and carbon nanotubes (CNTs) nanocomposition was applied to modify poly(vinylidene fluoride) (PVDF)-based membranes. The highly hydrophilic/oleophobic and fouling-resistant PVDF-g-IL/CNTs membranes with excellent separation efficiency were obtained by the nonsolvent-induced phase separation method with ethanol-water mixed solution as the coagulation bath. The grafted IL not only generated hydrophilic groups on PVDF chains but also acted together with the CNTs to induce the formation of hydrophilic ß-crystalline phase of PVDF, which significantly improved the hydrophilicity and pore structure of the modified PVDF membranes. As a result, the pure water flux of the optimal membrane increased up to 294.2 L m-2 h-1, which was 5.2 times greater than that of the pure PVDF membrane. Simultaneously, the electrostatic interaction of the positive IL and the integration of CNTs enhanced adsorption sites of the membranes, producing exceptional retention and adsorption of dye wastewater and oil-water emulsion. This study presents a straightforward and efficient approach for fabricating PVDF separation membranes, which have potential applications in the purification of various polluted wastewater.

Health-related social needs, medical financial hardship, and mortality risk among cancer survivors.

BACKGROUND: Cancer survivors may face challenges affording food, housing, and other living necessities, which are known as health-related social needs (HRSNs). However, little is known about the associations of HRSNs and mortality risk among adult cancer survivors. METHODS: Adult cancer survivors were identified from the 2013-2018 National Health Interview Survey (NHIS) and linked with the NHIS Mortality File with vital status through December 31, 2019. HRSNs, measured by food insecurity, and nonmedical financial worries (e.g., housing costs), was categorized as severe, moderate, and minor/none. Medical financial hardship, including material, psychological, and behavioral domains, was categorized as 2-3, 1, or 0 domains. Using age as the time scale, the associations of HRSNs and medical financial hardship and mortality risk were assessed with weighted adjusted Cox proportional hazards models. RESULTS: Among cancer survivors 18-64 years old (n = 5855), 25.5% and 18.3% reported moderate and severe levels of HRSNs, respectively; among survivors 65-79 years old (n = 5918), 15.6% and 6.6% reported moderate and severe levels of HRSNs, respectively. Among cancer survivors 18-64 years old, severe HRSNs was associated with increased mortality risk (hazards ratio [HR], 2.00; 95% confidence interval [CI], 1.36-2.93, p < .001; reference = minor/none) in adjusted analyses. Among cancer survivors 65-79 years old, 2-3 domains of medical financial hardship was associated with increased mortality risk (HR, 1.58; 95% CI, 1.13-2.20, p = .007; reference = 0 domain). CONCLUSIONS: HSRNs and financial hardship are associated with increased mortality risk among cancer survivors; comprehensive assessment of HRSN and financial hardship connecting patients with relevant services can inform efforts to mitigate adverse consequences of cancer.

Cancer diagnosis and treatment in working-age adults: Implications for employment, health insurance coverage, and financial hardship in the United States.

The rising costs of cancer care and subsequent medical financial hardship for cancer survivors and families are well documented in the United States. Less attention has been paid to employment disruptions and loss of household income after a cancer diagnosis and during treatment, potentially resulting in lasting financial hardship, particularly for working-age adults not yet age-eligible for Medicare coverage and their families. In this article, the authors use a composite patient case to illustrate the adverse consequences of cancer diagnosis and treatment for employment, health insurance coverage, household income, and other aspects of financial hardship. They summarize existing research and provide nationally representative estimates of multiple aspects of financial hardship and health insurance coverage, benefit design, and employee benefits, such as paid sick leave, among working-age adults with a history of cancer and compare them with estimates among working-age adults without a history of cancer from the most recently available years of the National Health Interview Survey (2019-2021). Then, the authors identify opportunities for addressing employment and health insurance coverage challenges at multiple levels, including federal, state, and local policies; employers; cancer care delivery organizations; and nonprofit organizations. These efforts, when informed by research to identify best practices, can potentially help mitigate the financial hardship associated with cancer.

Loneliness and Mortality Risk Among Cancer Survivors in the United States: A Retrospective, Longitudinal Study.

BACKGROUND: Loneliness, a subjective feeling of being isolated, is a prevalent concern for elderly people and more so among cancer survivors because a cancer diagnosis and its subsequent treatment may result in long-term adverse health effects. This study aimed to examine the association of loneliness and mortality risk among cancer survivors in the United States. METHODS: We identified a longitudinal cohort of cancer survivors aged ≥50 years from the nationally representative panel surveys of the 2008-2018 Health and Retirement Study. Follow-up for vital status was through 2020. Loneliness was measured using an 11-item abbreviated version of the UCLA Loneliness Scale (Version 3), including questions about lacking companionship and feeling isolated from others. A score was assigned according to the responses to each question, with 1 for least lonely, 2 for moderately lonely, and 3 for the loneliest option. Items were summed to create total loneliness scores for each individual, which were categorized into 4 levels: 11-12 (low/no loneliness), 13-15 (mild loneliness), 16-19 (moderate loneliness), and 20-33 (severe loneliness) based on the sample distribution. Time-varying Cox proportional hazard models with age as a time scale were used to examine the association of loneliness and survival among cancer survivors. RESULTS: A total of 3,447 cancer survivors with 5,808 person-years of observation were included, with 1,402 (24.3%), 1,445 (24.5%), 1,418 (23.6%), and 1,543 (27.6%) reporting low/no, mild, moderate, and severe loneliness, respectively. Compared with survivors reporting low/no loneliness, survivors reporting greater loneliness had a higher mortality risk, with the highest adjusted hazard ratios (aHRs) among the loneliest group (aHR, 1.67 [95% CI, 1.25-2.23]; P=.004) following a dose-response association. CONCLUSIONS: Elevated loneliness was associated with a higher mortality risk among cancer survivors. Programs to screen for loneliness among cancer survivors and to provide resources and support are warranted, especially considering the widespread social distancing that occurred during the COVID-19 pandemic.

Incarceration History and Access to and Receipt of Health Care in the US.

Importance: People with a history of incarceration may experience barriers in access to and receipt of health care in the US. Objective: To examine the associations of incarceration history and access to and receipt of care and the contribution of modifiable factors (educational attainment and health insurance coverage) to these associations. Design, Setting, and Participants: Individuals with and without incarceration history were identified from the 2008 to 2018 National Longitudinal Survey of Youth 1979 cohort. Analyses were conducted from October 2022 to December 2023. Main Measures and Outcomes: Access to and receipt of health care were measured as self-reported having usual source of care and preventive service use, including physical examination, influenza shot, blood pressure check, blood cholesterol level check, blood glucose level check, dental check, and colorectal, breast, and cervical cancer screenings across multiple panels. To account for the longitudinal study design, we used the inverse probability weighting method with generalized estimating equations to evaluate associations of incarceration history and access to care. Separate multivariable models examining associations between incarceration history and receipt of each preventive service adjusted for sociodemographic factors; sequential models further adjusted for educational attainment and health insurance coverage to examine their contribution to the associations of incarceration history and access to and receipt of health care. Results: A total of 7963 adults with 41 614 person-years of observation were included in this study; of these, 586 individuals (5.4%) had been incarcerated, with 2800 person-years of observation (4.9%). Compared with people without incarceration history, people with incarceration history had lower percentages of having a usual source of care or receiving preventive services, including physical examinations (69.6% vs 74.1%), blood pressure test (85.6% vs 91.6%), blood cholesterol level test (59.5% vs 72.2%), blood glucose level test (61.4% vs 69.4%), dental check up (51.1% vs 66.0%), and breast (55.0% vs 68.2%) and colorectal cancer screening (65.6% vs 70.3%). With additional adjustment for educational attainment and health insurance, the associations of incarceration history and access to care were attenuated for most measures and remained statistically significant for measures of having a usual source of care, blood cholesterol level test, and dental check up only. Conclusions and Relevance: The results of this survey study suggest that incarceration history was associated with worse access to and receipt of health care. Educational attainment and health insurance may contribute to these associations. Efforts to improve access to education and health insurance coverage for people with an incarceration history might mitigate disparities in care.

COVID-19 vaccination, infection, and symptoms among cancer survivors in the United States.

The experiences of cancer survivors with the COVID-19 pandemic in the United States during 2021 and 2022, when vaccinations became widely available, are largely undocumented. Using nationally representative survey data in 2021 and 2022, we found that compared with adults without a cancer history, cancer survivors were more likely to have at least 2 COVID-19 vaccines (2021: 66.6% vs 62.3%, P = .003; 2022: 77.0% vs 72.4%, P < .001) and as likely to have a COVID-19 infection history (2021: 14.1% vs 14.2%, P = .93; 2022: 39.9% vs 39.3%, P = .55) but, once infected, were more likely to develop moderate to severe symptoms (2021: 62.5% vs 54.2%, P = .02; 54.5% vs 61.3%; P = .13). Among cancer survivors, younger age, lower educational attainment, lack of health insurance, and more comorbidities were statistically significantly associated with lower vaccination rates (P < .001). Among infected cancer survivors, being female and younger were associated with higher likelihood of developing moderate to severe symptoms (P < .001). Our findings suggest tailored efforts to prevent and control COVID-19 infections for cancer survivors.

Importance of Patient Health Insurance Coverage and Out-of-Pocket Costs for Genomic Testing in Oncologists' Treatment Decisions.

PURPOSE: Use of genomic testing, especially multimarker panels, is increasing in the United States. Not all tests and related treatments are covered by health insurance, which can result in substantial patient out-of-pocket (OOP) costs. Little is known about oncologists' treatment decisions with respect to patient insurance coverage and OOP costs for genomic testing. METHODS: We identified 1,049 oncologists who used multimarker tumor panels from the 2017 National Survey of Precision Medicine in Cancer Treatment. Separate multivariable ordinal logistic regressions examined associations of oncologist-, practice-, and area-level characteristics and oncologists' ratings of importance (very, somewhat, or a little/not important) of insurance coverage and OOP costs for genomic testing in treatment decisions, adjusting for oncologist years of experience, sex, race and ethnicity, specialty, use of next-generation sequencing (NGS) tests, region, tumor boards, patient insurance mix, and area-level socioeconomic characteristics. RESULTS: Among oncologists, 47.3%, 32.7%, and 20.0% reported that patient insurance coverage for genomic testing was very, somewhat, or a little/not important, respectively, in treatment decisions. In addition, 56.9%, 28.0%, and 15.2% reported that OOP costs for testing were very, somewhat, or a little/not important, respectively. In adjusted analyses, oncologists who used NGS tests were more likely to report patient insurance and OOP costs as important (odds ratio [OR], 2.00 [95% CI, 1.16 to 3.45] and OR, 2.12 [95% CI, 1.22 to 3.68], respectively) in treatment decisions compared with oncologists who did not use these tests, as were oncologists who treated solid tumors, rather than only hematological cancers. More years of experience and higher percentages of Medicaid or self-paid/uninsured patients in the practice were associated with reporting insurance coverage (OR, 1.43 [95% CI, 1.09 to 1.89]) and OOP costs (OR, 1.51 [95% CI, 1.13 to 2.01]) as important. Oncologists in practices with molecular tumor boards for genomic tests were less likely to report coverage (OR, 0.63 [95% CI, 0.47 to 0.85]) and OOP costs (OR, 0.72 [95% CI, 0.53 to 0.97]) as important than their counterparts in practices without these tumor boards. CONCLUSION: Most oncologists rate patient health insurance and OOP costs for genomic tests as important considerations in subsequent treatment recommendations. Modifiable factors associated with these ratings can inform interventions to support patient-physician decision making about care.

Assessment of Changes in Cancer Treatment During the First Year of the COVID-19 Pandemic in the US.

Importance: The COVID-19 pandemic led to disruptions in access to health care, including cancer care. The extent of changes in receipt of cancer treatment is unclear. Objective: To evaluate changes in the absolute number, proportion, and cancer treatment modalities provided to patients with newly diagnosed cancer during 2020, the first year of the pandemic. Design, Setting, and Participants: In this cohort study, adults aged 18 years and older diagnosed with any solid tumor between January 1, 2018, and December 31, 2020, were identified using the National Cancer Database. Data analysis was conducted from September 19, 2022, to July 28, 2023. Exposure: First year of the COVID-19 pandemic. Main Outcomes and Measures: The expected number of procedures for each treatment modality (surgery, radiotherapy, chemotherapy, immunotherapy, and hormonal therapy) in 2020 were calculated using historical data (January 1, 2018, to December 31, 2019) with the vector autoregressive method. The difference between expected and observed numbers was evaluated using a generalized estimating equation under assumptions of the Poisson distribution for count data. Changes in the proportion of different types of cancer treatments initiated in 2020 were evaluated using the additive outlier method. Results: A total of 3 504 342 patients (1 214 918 in 2018, mean [SD] age, 64.6 [13.6] years; 1 235 584 in 2019, mean [SD] age, 64.8 [13.6] years; and 1 053 840 in 2020, mean [SD] age, 64.9 [13.6] years) were included. Compared with expected treatment from previous years' trends, there were approximately 98 000 fewer curative intent surgical procedures performed, 38 800 fewer chemotherapy regimens, 55 500 fewer radiotherapy regimens, 6800 fewer immunotherapy regimens, and 32 000 fewer hormonal therapies initiated in 2020. For most cancer sites and stages evaluated, there was no statistically significant change in the type of cancer treatment provided during the first year of the pandemic, the exception being a statistically significant decrease in the proportion of patients receiving breast-conserving surgery and radiotherapy with a simultaneous statistically significant increase in the proportion of patients undergoing mastectomy for treatment of stage I breast cancer during the first months of the pandemic. Conclusions and Relevance: In this large national cohort study, a significant deficit was noted in the number of cancer treatments provided in the first year of the COVID-19 pandemic. Data indicated that this deficit in the number of cancer treatments provided was associated with decreases in the number of cancer diagnoses, not changes in treatment strategies.

Employment and workdays lost among spouses of cancer survivors: Intersection with gender across cancer treatment status.

BACKGROUND: Cancer patients and survivors have high care needs, often provided by a spouse or partner. The purpose of this study was to elucidate how employment and work loss patterns differed across cancer history/treatment status and gender. METHODS: Using nationally representative data from the Medical Expenditure Panel Survey (2011, 2016, and 2017), the authors linked data across married participants and categorized them by spouses' cancer treatment status (no cancer history, on treatment for cancer, off treatment for cancer). Multivariable logistic and zero-inflated negative binomial regressions were used to assess the associations among cancer history/treatment status, gender, and employment outcomes (employment status and workdays lost to care for self or others). RESULTS: For men, employment did not differ significantly by cancer history/treatment status (on treatment: odds ratio [OR], 0.58; 95% confidence interval [CI], 0.33-1.02, off treatment: OR, 0.84; 95% CI, 0.62-1.14 vs. no cancer history). For women, employment was not significantly different when the spouse was on treatment for cancer compared to no cancer history (OR, 0.78; 95% CI, 0.33-1.86]) but was significantly increased for women whose spouse was off treatment (OR, 1.39; 95% CI, 1.05-1.84). Among employed participants, women whose spouse was on cancer treatment were nine times more likely to take days off work to provide care (OR, 9.52; 95% CI, 3.94-23.03) and took more than three times as many days off to care for others (OR, 3.21; 95% CI, 2.07-4.97) as men whose spouse had no cancer history. CONCLUSIONS: Wives of cancer survivors are at increased risk of work loss, with implications for their financial and psychological well-being. Employers, policymakers, and clinicians have opportunities to support working caregivers.

Identification and characterization of a novel 6'-N-aminoglycoside acetyltransferase AAC(6')-Va from a clinical isolate of Aeromonas hydrophila.

Background: Aeromonas species have been identified as agents responsible for various diseases in both humans and animals. Multidrug-resistant Aeromonas strains pose a significant public health threat due to their emergence and spread in clinical settings and the environment. The aim of this study was to determine a novel resistance mechanism against aminoglycoside antimicrobials in a clinical isolate. Methods: The function of aac(6')-Va was verified by gene cloning and antibiotic susceptibility tests. To explore the in vivo activity of the enzyme, recombinant proteins were expressed, and enzyme kinetics were tested. To determine the molecular background and mechanism of aac(6')-Va, whole-genome sequencing and bioinformatic analysis were performed. Results: The novel aminoglycoside N-acetyltransferase gene aac(6')-Va confers resistance to several aminoglycosides. Among the antimicrobials tested, ribostamycin showed the highest increase (128-fold) in the minimum inhibitory concentration (MIC) compared with the control strains. According to the MIC results of the cloned aac(6')-Va, AAC(6')-Va also showed the highest catalytic efficiency for ribostamycin [kcat/Km ratio = (3.35 ± 0.17) × 104 M-1 s-1]. Sharing the highest amino acid identity of 54.68% with AAC(6')-VaIc, the novel aminoglycoside N-acetyltransferase constituted a new branch of the AAC(6') family due to its different resistance profiles. The gene context of aac(6')-Va and its close relatives was conserved in the genomes of species of the genus Aeromonas. Conclusion: The novel resistance gene aac(6')-Va confers resistance to several aminoglycosides, especially ribostamycin. Our finding of a novel resistance gene in clinical A. hydrophila will help us develop more effective treatments for this pathogen's infections.

Qa-SNARE syntaxin 18 mediates lipid droplet fusion with SNAP23 and SEC22B.

Lipid droplets (LDs) are dynamic lipid storage organelles that can sense and respond to changes in systemic energy balance. The size and number of LDs are controlled by complex and delicate mechanisms, among which, whether and which SNARE proteins mediate LD fusion, and the mechanisms governing this process remain poorly understood. Here we identified a SNARE complex, syntaxin 18 (STX18)-SNAP23-SEC22B, that is recruited to LDs to mediate LD fusion. STX18 targets LDs with its transmembrane domain spanning the phospholipid monolayer twice. STX18-SNAP23-SEC22B complex drives LD fusion in adiposome lipid mixing and content mixing in vitro assays. CIDEC/FSP27 directly binds STX18, SEC22B, and SNAP23, and promotes the lipid mixing of SNAREs-reconstituted adiposomes by promoting LD clustering. Knockdown of STX18 in mouse liver via AAV resulted in smaller liver and reduced LD size under high-fat diet conditions. All these results demonstrate a critical role of the SNARE complex STX18-SNAP23-SEC22B in LD fusion.

Identification and characterization of a novel ß-lactamase gene, blaAMZ-1, from Achromobacter mucicolens.

Background: Achromobacter is a genus of gram-negative bacteria that can act as opportunistic pathogens. Recent studies have revealed that some species of Achromobacter show inherent resistance to ß-lactams, but the resistance mechanisms of Achromobacter mucicolens have rarely been reported. Method: The bacterium was isolated using standard laboratory procedures. The agar dilution method was used to determine the minimum inhibitory concentrations (MICs). Genome sequencing was performed using the PacBio RS II and Illumina HiSeq 2500 platforms, and the Comprehensive Antibiotic Resistance Database (CARD) was used to annotate the drug resistance genes. The localization of the novel ß-lactamase AMZ-1 was determined, and its characteristics were determined via molecular cloning and enzyme kinetic analysis. The phylogenetic relationship and comparative genomic analysis of the resistance gene-related sequences were also analyzed. Result: Achromobacter mucicolens Y3, isolated from a goose on a farm in Wenzhou, showed resistance to multiple antibiotics, including penicillins and cephalosporins. BlaAMZ-1 showed resistance to amoxicillin, penicillin G, ampicillin, cephalothin and cefoxitin, and the resistance activity could be inhibited by ß-lactamase inhibitors. Enzyme kinetic analysis results showed that AMZ-1 has hydrolytic activity against a wide range of substrates, including cephalothin, amoxicillin, penicillin G, and cefoxitin but not ampicillin. The hydrolytic activity of AMZ-1 was greatly inhibited by avibactam but much more weakly inhibited by tazobactam. Mobile genetic elements could not be found around the blaAMZ-1-like genes, which are conserved on the chromosomes of bacteria of the genus Achromobacter. Conclusion: In this study, a novel AmpC gene, blaAMZ-1, from the animal-origin bacterium A. mucicolens Y3 was identified and characterized. It conferred resistance to some penicillins and first- and second-generation cephalosporins. The identification of this novel resistance gene will be beneficial for the selection of effective antimicrobials to treat associated infections.

Association of Employment Disruptions and Financial Hardship Among Individuals Diagnosed with Cancer in the United States: Findings from a Nationally Representative Study.

Financial hardship (FH), defined as adverse patient effects due to cancer costs, is experienced by approximately half of individuals diagnosed with cancer. Many individuals diagnosed with cancer also experience disruptions with their employment. This study examines associations of employment disruptions and FH among a nationally representative sample of individuals diagnosed with cancer in the United States. We utilized 2016/2017 Medical Expenditure Panel Survey Experiences with Cancer data from individuals who worked for pay following cancer diagnosis. Employment disruption included taking extended paid time off work; switching to part-time/less demanding jobs; and/or retiring early due to cancer diagnosis/treatment. FH domains included: material (e.g., borrowing money/financial sacrifices); psychologic (e.g., worrying about medical bills/income); and behavioral (delaying/forgoing healthcare services because of cost). Multivariable logistic regression analyses determined associations of employment disruption and FH. Among 732 individuals with a cancer history, 47.4% experienced employment disruptions; 55.9% experienced any FH. Any FH was significantly more common among individuals with versus without employment disruptions across multiple measures and domains (68.7% vs. 44.5%; P value of difference <0.0001). Individuals with employment disruptions were more likely to have any FH [OR, 2.38; 95% confidence interval (CI), 1.62-3.52] and more FHs (OR, 2.76; 95% CI, 1.96-3.89]. This study highlights that employment disruptions are common and significantly associated with multiple domains of FH among individuals with a cancer history. Employer workplace accommodation, physician discussions regarding potential impacts of cancer care on employment, and other policies to minimize employment disruptions among individuals diagnosed with cancer may reduce FH in this vulnerable population. Significance: Individuals diagnosed with cancer may have employment disruptions; they may also develop FHs. People with cancer who have employment changes are more likely to also have FHs. Physicians and employers can help individuals with cancer through advancing planning, workplace assistance, and improved medical leave and insurance policies.

Medicaid expansion is associated with treatment receipt, timeliness, and outcomes among young adults with breast cancer.

Female breast cancer is a common cancer in young adults, an age group with the highest uninsured rate. Among 51 675 young adult women (ages 18-39 years) diagnosed with breast cancer between 2011 and 2018 in the National Cancer Database, we estimated changes in guideline-concordant treatment receipt, treatment timeliness, and survival associated with the Affordable Care Act Medicaid expansion. Of young adults with stage I-III estrogen receptor-positive or progesterone receptor-positive breast cancer, Medicaid expansion was associated with a net increase of 2.42 percentage points (95% confidence interval [CI] = 0.56 to 4.28 percentage points) in the percentage receiving endocrine therapy. Among all young adults with stage I-III breast cancer, Medicaid expansion was associated with a net reduction of 1.65 percentage points (95% CI = 0.08 to 3.22 percentage points) in treatment delays defined as treatment initiation of at least 60 days after diagnosis and a net increase of 1.00 percentage points (95% CI = 0.21 to 1.79 percentage points) in 2-year overall survival. Our study provides evidence of benefit in cancer care and outcomes from Medicaid expansion among the young adult population.

Identification and characterization of a novel chromosomal aminoglycoside 3'-O-phosphotransferase, APH(3')-Id, from Kluyvera intermedia DW18 isolated from the sewage of an animal farm.

Background: Aminoglycosides, as important clinical antimicrobials, are used as second-line drugs for treating multidrug-resistant tuberculosis or combined with ß-lactam drugs for treating severe infections such as sepsis. Aminoglycoside-modifying enzyme (AME) is the most important mechanism of aminoglycoside resistance and deserves more attention. Methods: The bacterium Kluyvera intermedia DW18 was isolated from the sewage of an animal farm using the conventional method. The agar dilution method was used to determine the minimum inhibitory concentrations (MICs) of antimicrobials. A novel resistance gene was cloned, and the enzyme was expressed. The kinetic parameters were measured by a SpectraMax M5 multifunctional microplate reader. Bioinformatic analysis was performed to reveal the genetic context of the aph(3')-Id gene and its phylogenetic relationship with other AMEs. Results: A novel aminoglycoside 3'-O-phosphotransferase gene designated aph(3')-Id was identified in K. intermedia DW18 and shared the highest amino acid identity of 77.49% with the functionally characterized aminoglycoside 3'-O-phosphotransferase APH(3')-Ia. The recombinant plasmid carrying the novel resistance gene (pMD19-aph(3')-Id/E. coli DH5α) showed 1,024-, 512-, 128- and 16-fold increased MIC levels for kanamycin, ribostamycin, paromomycin and neomycin, respectively, compared with the reference strain DH5α. APH(3')-Id showed the highest catalytic efficiency for ribostamycin [kcat/Km of (4.96 ± 1.63) × 105 M-1/s-1], followed by paromomycin [kcat/Km of (2.18 ± 0.21) × 105 M-1/s-1], neomycin [kcat/Km of (1.73 ± 0.20) × 105 M-1/s-1], and kanamycin [kcat/Km of (1.10 ± 0.18) × 105 M-1/s-1]. Three conserved functional domains of the aminoglycoside phosphotransferase family and ten amino acid residues responsible for the phosphorylation of kanamycin were found in the amino acid sequence of APH(3')-Id. No mobile genetic element (MGE) was discovered surrounding the aph(3')-Id gene. Conclusion: In this work, a novel aminoglycoside 3'-O-phosphotransferase gene designated aph(3')-Id encoded in the chromosome of the environmental isolate Kluyvera intermedia DW18 was identified and characterized. These findings will help clinicians select effective antimicrobials to treat infections caused by pathogens with this kind of resistance gene.

Construction of a multi-layer protection of CS polymer brush grafted DA@CNTs coating on PVDF membrane for effective removal of dye effluent.

In the process of removing dye wastewater, the membrane surface is susceptible to contamination, resulting in reduced performance and limited dye separation efficiency. A single hydrophilic modification layer is not enough to achieve effective separation of different types of dyes. The present research designed a "double layer protection" method in order to overcome the above deficiencies. A solution of dopamine (DA) coated carbon nanotubes (CNTs-COOH) was covered on the surface of the polyvinylidene fluoride (PVDF) membrane by deposition, followed by grafting a layer of chitosan (CS) polymer brushes on its surface. The spatial double layer structure provides an excellent barrier effect and effectively reduces the contamination of dyes. When filtering different types of dyes, effective filtration of anionic and cationic dyes through the electrostatic effect of the first layer, the adsorption of CNTs in the second layer and the hydration layer of both layers. All membranes have excellent rejection properties. More importantly, the membranes also had good chemical and mechanical stability and their serviceability was not degraded. Therefore, the prepared PVDF-based multi-layer composite membranes behave a potential application prospect in the wastewater purification field.

Changes in cancer diagnoses and stage distribution during the first year of the COVID-19 pandemic in the USA: a cross-sectional nationwide assessment.

BACKGROUND: The emergence of COVID-19 disrupted health care, with consequences for cancer diagnoses and outcomes, especially for early stage diagnoses, which generally have favourable prognoses. We aimed to examine nationwide changes in adult cancer diagnoses and stage distribution during the first year of the COVID-19 pandemic by cancer type and key sociodemographic factors in the USA. METHODS: In this cross-sectional study, adults (aged ≥18 years) newly diagnosed with a first primary malignant cancer between Jan 1, 2018, and Dec 31, 2020, were identified from the US National Cancer Database. We included individuals across 50 US states and the District of Columbia who were treated in hospitals that were Commission on Cancer-accredited during the study period. Individuals whose cancer stage was 0 (except for bladder cancer), occult, or without an applicable American Joint Committee on Cancer staging scheme were excluded. Our primary outcomes were the change in the number and the change in the stage distribution of new cancer diagnoses between 2019 (Jan 1 to Dec 31) and 2020 (Jan 1 to Dec 31). Monthly counts and stage distributions were calculated for all cancers combined and for major cancer types. We also calculated annual change in stage distribution from 2019 to 2020 and adjusted odds ratios (aORs) using multivariable logistic regression, adjusted for age group, sex, race and ethnicity, health insurance status, comorbidity score, US state, zip code-level social deprivation index, and county-level age-adjusted COVID-19 mortality in 2020. Separate models were stratified by sociodemographic and clinical factors. FINDINGS: We identified 2 404 050 adults who were newly diagnosed with cancer during the study period (830 528 in 2018, 849 290 in 2019, and 724 232 in 2020). Mean age was 63·5 years (SD 13·5) and 1 287 049 (53·5%) individuals were women, 1 117 001 (46·5%) were men, and 1 814 082 (75·5%) were non-Hispanic White. The monthly number of new cancer diagnoses (all stages) decreased substantially after the start of the COVID-19 pandemic in March, 2020, although monthly counts returned to near pre-pandemic levels by the end of 2020. The decrease in diagnoses was largest for stage I disease, leading to lower odds of being diagnosed with stage I disease in 2020 than in 2019 (aOR 0·946 [95% CI 0·939-0·952] for stage I vs stage II-IV); whereas, the odds of being diagnosed with stage IV disease were higher in 2020 than in 2019 (1·074 [1·066-1·083] for stage IV vs stage I-III). This pattern was observed in most cancer types and sociodemographic groups, although was most prominent among Hispanic individuals (0·922 [0·899-0·946] for stage I; 1·110 [1·077-1·144] for stage IV), Asian American and Pacific Islander individuals (0·924 [0·892-0·956] for stage I; 1·096 [1·052-1·142] for stage IV), uninsured individuals (0·917 [0·875-0·961] for stage I; 1·102 [1·055-1·152] for stage IV), Medicare-insured adults younger than 65 years (0·909 [0·882-0·937] for stage I; 1·105 [1·068-1·144] for stage IV), and individuals living in the most socioeconomically deprived areas (0·931 [0·917-0·946] for stage I; 1·106 [1·087-1·125] for stage IV). INTERPRETATION: Substantial cancer underdiagnosis and decreases in the proportion of early stage diagnoses occurred during 2020 in the USA, particularly among medically underserved individuals. Monitoring the long-term effects of the pandemic on morbidity, survival, and mortality is warranted. FUNDING: None.

BlaPSZ-1, a novel AmpC gene identified from a Pantoea isolate.

Background: Pantoea species of the family Erwiniaceae are well-known plant pathogens and animal and human conditional pathogens. Due to the widespread and continuous use of antimicrobials, multidrug-resistant strains continue to emerge, making clinical treatment difficult; therefore, there is an increasing need to clarify the mechanisms of drug resistance. Methods: A rabbit anal fecal sample was collected by a swab and the streak plate method was used to isolate single colonies. The standard agar dilution method was used to determine the minimum inhibitory concentrations (MICs) against antimicrobials. The complete genome sequence of the bacterium was obtained using Next-Generation Sequencing platforms. The potential resistance gene was annotated based on the Comprehensive Antibiotic Resistance Database (CARD) and verified by molecular cloning. The ß-lactamase PSZ-1 was expressed via the pCold I expression vector and its enzyme kinetic parameters were analyzed. The genetic environment and evolutionary process of the novel resistance gene-related sequences were analyzed by bioinformatic methods. Results: The isolate Pantoea endophytica X85 showed some degree of resistance to penicillins as well as cephalosporins. A novel AmpC resistance gene, designated blaPSZ-1 in this research, was identified to be encoded in the plasmid (pPEX85) of P. endophytica X85. BlaPSZ-1 showed resistance to penicillins and several first-, second-and third-generation cephalosporins as well as aztreonam, but it did not show resistance to the fourth-generation cephalosporins or carbapenems tested. Enzyme kinetic assays revealed that it could hydrolyze amoxicillin, penicillin G, cephalothin, and cefazolin, and its hydrolytic activity could be strongly inhibited by the inhibitor avibactam, which was generally consistent with antimicrobial susceptibility testing results. No hydrolytic activity was observed for third-generation cephalosporins or aztreonam. Conclusion: In this study, a novel AmpC ß-lactamase gene, designated blaPSZ-1, was characterized and it was encoded in the plasmid of the bacterium P. endophytica X85. It shows resistance to penicillins and several cephalosporins. The discovery of novel drug resistance mechanisms can help guide the scientific use of drugs in animal husbandry and clinical practice, effectively avoiding the abuse of antimicrobials and thus preventing the further development and spread of bacterial resistance.