Ambient air pollution and survival in childhood cancer: A nationwide survival analysis.

BACKGROUND: Particulate matter consisting of fine particles measuring 2.5 microns or less in diameter (PM2.5), a component of air pollution, has been linked to adverse health outcomes. The objective of this study was to assess the association between ambient PM2.5 exposure and survival in children with cancer in the United States. METHODS: Individuals aged birth to 19 years who were diagnosed with cancer between January 1, 2004, and December 31, 2019, were selected from the National Cancer Database. The association between the annual PM2.5 level at the patient's zip code of residence at the time of diagnosis and overall survival was evaluated using time-varying Cox proportional hazards models (crude and adjusted for diagnosis year and age). To address concerns that exposure to air pollution is correlated with other social determinants of health, the authors tested the association between PM2.5 levels and survival among sociodemographic subgroups. RESULTS: Of the 172,550 patients included, 27,456 (15.9%) resided in areas with annual PM2.5 concentrations above the US Environmental Protection Agency (EPA) annual PM2.5 standard of 12 µg/m3. Residing in these high-pollution areas was associated with worse overall survival (adjusted hazard ratio [aHR], 1.06; 95% confidence interval [CI], 1.012-1.10). Similarly, when PM2.5 was evaluated as a linear measure, each unit increase in PM2.5 exposure was associated with worse survival (aHR, 1.011; CI, 1.005-1.017). Exposure to PM2.5 at levels above the EPA standards was also significantly associated with worse overall survival among sociodemographic subgroups. CONCLUSIONS: Exposure to PM2.5 was significantly associated with worse overall survival among children with cancer, even at levels below EPA air quality standards. These results underscore the importance of setting appropriate air quality standards to protect the health of this sensitive population. PLAIN LANGUAGE SUMMARY: The authors investigated how living in areas with high air pollution (defined as particulate matter consisting of fine particles measuring 2.5 microns or less in diameter; PM2.5) affects the overall survival of children with cancer in the United States. The results indicated that children living in areas with higher PM2.5 levels, and even at levels below prior and current US Environmental Protection Agency standards, had lower survival rates than children living in areas with lower levels of PM2.5. This finding emphasizes the need for stricter air quality standards to better protect children, particularly those with serious health conditions like childhood cancer.

Association of Family Member Incarceration During Childhood and Smoking and Unhealthy Drinking Behaviors, Access to Care, and Functional Status Among Adults in the United States.

IMPORTANCE: Incarceration can result in adverse socioeconomic and health consequences for individuals who have been incarcerated; these consequences extend to their children and may have impacts into later adulthood. OBJECTIVE: To examine the association of family member incarceration (FMI) during childhood and smoking and unhealthy drinking behaviors, access to care, and functional status in later adulthood. DESIGN AND PARTICIPANTS: Adults aged 18-64 and ≥ 65 with and without FMI during childhood from 42 states and Washington DC from the 2019-2022 Behavioral Risk Factor Surveillance System. MAIN MEASURES: Having FMI history was defined as "living with anyone during childhood who served time or was sentenced to serve time in a prison, jail, or other correctional facility." Study outcomes included 1) smoking and unhealthy drinking behaviors, 2) access to care (health insurance coverage, care affordability, having a usual source of care, and use of preventive services), and 3) functional status (e.g., having difficulty walking or climbing stairs). KEY RESULTS: After adjusting for demographic characteristics and other adverse childhood experiences, compared to adults without FMI, adults aged 18-64 with FMI were more likely to report any history of smoking or unhealthy drinking (adjusted odds ratio (AOR): 1.19, 95% confidence interval (CI): 1.11-1.28), any access to care problems (AOR: 1.26, 95% CI: 1.12-1.42), and any functional limitations (AOR: 1.18, 95% CI: 1.10-1.28); adults aged ≥ 65 with FMI reported higher likelihood of reporting any smoking or unhealthy drinking behaviors (AOR: 1.23, 95% CI: 1.05-1.43) and impaired functional status (AOR: 1.30, 95% CI: 1.10-1.54). Associations were attenuated after additional adjustment for socioeconomic measures, especially educational attainment, but remained statically significant for multiple outcomes. CONCLUSIONS: FMI during childhood was associated with adverse health-related outcomes for adults of all ages. Developing programs to improve access to education and economic opportunities for adults with FMI may help mitigate the disparities.

APH(3')-Ie, an aminoglycoside-modifying enzyme discovered in a rabbit-derived Citrobacter gillenii isolate.

Background: Aminoglycoside-modifying enzymes (AMEs) play an essential role in bacterial resistance to aminoglycoside antimicrobials. With the development of sequencing techniques, more bacterial genomes have been sequenced, which has aided in the discovery of an increasing number of novel resistance mechanisms. Methods: The bacterial species was identified by 16S rRNA gene homology and average nucleotide identity (ANI) analyses. The minimum inhibitory concentration (MIC) of each antimicrobial was determined by the agar dilution method. The protein was expressed with the pCold I vector in E. coli BL21, and enzyme kinetic parameters were examined. The whole-genome sequence of the bacterium was obtained via the Illumina and PacBio sequencing platforms. Reconstruction of the phylogenetic tree, identification of conserved functional residues, and gene context analysis were performed using the corresponding bioinformatic techniques. Results: A novel aminoglycoside resistance gene, designated aph(3')-Ie, which confers resistance to ribostamycin, kanamycin, sisomicin and paromomycin, was identified in the chromosome of the animal bacterium Citrobacter gillenii DW61, which exhibited a multidrug resistance phenotype. APH(3')-Ie showed the highest amino acid identity of 74.90% with the functionally characterized enzyme APH(3')-Ia. Enzyme kinetics analysis demonstrated that it had phosphorylation activity toward four aminoglycoside substrates, exhibiting the highest affinity (K m, 4.22 ± 0.88 µM) and the highest catalytic efficiency [k cat/K m, (32.27 ± 8.14) × 104] for ribomycin. Similar to the other APH(3') proteins, APH(3')-Ie contained all the conserved functional sites of the APH family. The aph(3')-Ie homologous genes were present in C. gillenii isolates from different sources, including some of clinical significance. Conclusion: In this work, a novel chromosomal aminoglycoside resistance gene, designated aph(3')-Ie, conferring resistance to aminoglycoside antimicrobials, was identified in a rabbit isolate C. gillenii DW61. The elucidation of the novel resistance mechanism will aid in the effective treatment of infections caused by pathogens carrying such resistance genes.

Health insurance literacy among patients receiving outpatient cancer treatment.

BACKGROUND: This study examines patients' understanding of health insurance terms and concepts and quantifies health insurance literacy (HIL) levels by key sociodemographic factors. METHODS: This study included 393 adult patients with cancer (>18 years old) receiving treatment in two ambulatory infusion centers: Mayo Clinic in Phoenix, Arizona and the University of Mississippi Medical Center in Jackson, Mississippi. Respondents' perceptions of their HIL were assessed using the Health Insurance Literacy Measure (HILM), a validated 21-item measure of a consumer's ability to select and use health insurance (HIL self-efficacy). Respondents' knowledge of health insurance concepts (HIL knowledge) was measured using 10 items created by the Kaiser Family Foundation. The number of correct answers was categorized into three levels: 0-4 (low knowledge), 5-6 (moderate knowledge), and 7-10 (high knowledge). Multivariable logistic regressions were used to compare correct answers to HIL knowledge questions by HIL self-efficacy. RESULTS: Nearly three-quarters of patients had high HIL self-efficacy and high HIL knowledge (70.5%), understanding basic insurance terms, such as premiums and deductibles. Relatively low percentages of patients correctly answered questions about the meaning of provider networks, health insurance formularies, and calculating out-of-pocket spending in scenarios when insurers pay a portion of allowed charges. Lower HIL knowledge was more common among patients with less educational attainment (

Construction of CS-SDAEM long-chain polysaccharide derivative on TA@CNTs coated PVDF membrane with effective oil-water emulsion purification and low contamination rate.

Currently, the most effective way to improve the anti-fouling performance of water treatment separation membrane is to enhance the hydrophilicity of the membrane surface, but it can still cause contamination, leading to the occurrence of flux reduction. The construction of a strong hydration layer to resist wastewater contamination is still a challenging task. In this study, a defect-free hydration layer barrier was achieved by grafting chitosan polysaccharide derivatives (CS-SDAEM) on the membrane, which achieved in effective fouling prevention and low flux decline rate. A layer of tannic acid-coated carbon nanotubes (TA@CNTs) has been uniformly deposited on the commercial PVDF membrane so that the surface was rich in -COOH groups, providing sufficient reaction sites. These reactive groups facilitate the grafting of amphiphilic polymers onto the membrane. This modification strategy achieved in enhancing the antifouling performance. The modified membrane achieved low contamination rate with DR of 16.9 % for wastewater filtration, and the flux recovery rate was above 95 % with PWF of 1100 (L·m-2·h-1). The membrane had excellent anti-fouling performance, which provided a new route for the future development of water treatment membrane.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.