Association of Medicaid Expansion With Timely Receipt of Treatment and Survival Among Patients With HR-Negative, HER2-Positive Breast Cancer.

BACKGROUND: Hormone receptor (HR)-negative, HER2-positive (also called HER2-enriched) breast cancer has no worse prognosis than other breast cancers if it is treated with HER2-targeted therapy. Medicaid expansion under the Affordable Care Act (ACA) has been shown to be associated with improved access to care and outcomes for many cancers, but its association with receipt of care for HR-negative, HER2-positive breast cancer is unknown. We examined the association of Medicaid expansion with receipt of guideline-concordant treatment, time to treatment initiation, and survival among nonelderly women newly diagnosed with HR-negative, HER2-positive breast cancer. PATIENTS AND METHODS: Women aged 18 to 62 years newly diagnosed with HR-negative, HER2-positive breast cancer between 2010 and 2018 were identified from the National Cancer Database. Outcomes included receipt of stage-based guideline-concordant treatment, timely initiation of treatment (<30 days, <60 days, <90 days from diagnosis), and stage-specific 2-year overall survival. A difference-in-differences (DID) analytic approach compared outcome changes following Medicaid expansion in expansion versus nonexpansion states. Multivariable linear probability models were used to estimate treatment outcomes, and flexible parametric survival models were used to evaluate survival, adjusting for sociodemographic and clinical confounders. RESULTS: A total of 31,401 patients were included. Medicaid expansion was associated with an increase of 0.58 percentage points (ppt; 95% CI, 0.01-1.16) in receipt of guideline-concordant treatment overall, a 2.43-ppt (95% CI, 0.68-4.18) increase in initiating guideline-concordant treatment <60 days after diagnosis, and a 1.17-ppt (95% CI, 0.02-2.32) increase in 2-year survival rate. The increase in 2-year survival associated with Medicaid expansion was most prominent for patients with stage III disease (DID, 3.81; 95% CI, 0.82-6.80). CONCLUSIONS: Medicaid expansion was associated with improved care and survival for patients with HR-negative, HER2-positive breast cancer, an aggressive cancer type for which prognosis largely depends on access to effective treatment.

Association of health insurance coverage disruptions and breast and colorectal cancer screening.

BACKGROUND: Health insurance coverage is critical for ensuring access to recommended health care in the United States. This study investigated the associations of health insurance coverage disruptions, also known as coverage churn, and receipt of breast and colorectal cancer screening. METHODS: Adults who were age-eligible and younger than 65 years (range, 50-64 years) for breast (n = 17,128 women) and colorectal (n = 32,562 individuals) cancer screening were identified from 5 years of the National Health Interview Survey. Adults were categorized into five groups based on insurance type at survey (private, public, none) and prior coverage disruptions within the past year. Screening outcomes included: (1) ever-screened, (2) past-year screening, and (3) guideline-concordant screening. Separate multivariate logistic regression models were used to evaluate the associations between insurance coverage disruptions and cancer screening. RESULTS: Among adults who had coverage at the time of the survey, 3.1% with private insurance and 6.5% with public insurance reported prior coverage disruptions. Individuals without health insurance coverage had the lowest level of screening. Among individuals who had private coverage, prior disruptions were associated with lower guideline-concordant screening in adjusted analyses (breast cancer screening: adjusted prevalence ratio [aPR], 0.82; 95% confidence interval [CI], 0.75-0.89; colorectal cancer screening: aPR, 0.78; 95% CI, 0.72-0.86); among those who had public coverage, prior disruptions were also associated with lower guideline-concordant breast cancer screening (aPR, 0.73; 95% CI, 0.60-0.89) and colorectal cancer screening (aPR, 0.84; 95% CI, 0.72-0.99). CONCLUSIONS: Health insurance coverage disruptions were associated with lower past-year and guideline-concordant breast and colorectal cancer screening. The current findings underscore the importance of stable health insurance coverage to improve cancer screening and early detection when treatment is most effective.

County-level jail and state-level prison incarceration and cancer mortality in the United States.

This study examined the association of county-level jail and state-level prison incarceration rates and cancer mortality rates in the United States. Incarceration rates (1995-2018) were sourced from national data and categorized into quartiles. County- and state-level mortality rates (2000-2019) with invasive cancer as the underlying cause of death were obtained from the National Vital Statistics System. Compared with the first quartile (lowest incarceration rate), the second, third, and fourth quartiles (highest incarceration rate) of county-level jail incarceration rate were associated with 1.3%, 2.3%, and 3.9% higher county-level cancer mortality rates, respectively, in adjusted analyses. Compared with the first quartile, the second, third, and fourth quartiles of state-level prison incarceration rate were associated with 1.7%, 2.5%, and 3.9% higher state-level cancer mortality rates, respectively. Associations were more pronounced for liver and lung cancers. Addressing adverse effects of mass incarceration may potentially improve cancer outcomes in affected communities.

Accurate Long-Read RNA Sequencing Analysis Reveals the Key Pathways and Candidate Genes under Drought Stress in the Seed Germination Stage in Faba Bean.

Faba bean is an important pulse. It provides proteins for the human diet and is used in industrial foodstuffs, such as flours. Drought stress severely reduces the yield of faba bean, and this can be efficiently overcome through the identification and application of key genes in response to drought. In this study, PacBio and Illumina RNA sequencing techniques were used to identify the key pathways and candidate genes involved in drought stress response. During seed germination, a total of 17,927 full-length transcripts and 12,760 protein-coding genes were obtained. There were 1676 and 811 differentially expressed genes (DEGs) between the varieties E1 and C105 at 16 h and 64 h under drought stress, respectively. Six and nine KEGG pathways were significantly enriched at 16 h and 64 h under drought stress, which produced 40 and 184 nodes through protein-protein interaction (PPI) analysis, respectively. The DEGs of the PPI nodes were involved in the ABA (abscisic acid) and MAPK (mitogen-activated protein kinase) pathways, N-glycosylation, sulfur metabolism, and sugar metabolism. Furthermore, the ectopic overexpression of a key gene, AAT, encoding aspartate aminotransferase (AAT), in tobacco, enhanced drought tolerance. The activities of AAT and peroxidase (POD), the contents of cysteine and isoleucine, were increased, and the contents of malonaldehyde (MDA) and water loss decreased in the overexpressed plants. This study provides a novel insight into genetic response to drought stress and some candidate genes for drought tolerance genetic improvements in this plant.

Eurasian otters prefer to prey on religious released non-native fish on the Qinghai-Tibetan Plateau.

Religious wildlife release is prevalent worldwide, especially in Asia countries. It is one of the anthropogenic pathways to cause biological invasions. Religious fish release is common on the Qinghai-Tibetan Plateau, yet few studies have assessed the influences of religious fish release on local species. In Yushu, a city on the Qinghai-Tibetan Plateau, we interviewed local people, conducted fish trap surveys in local rivers, and examined the diet of Eurasian otters Lutra lutra using a fecal DNA metabarcoding approach. We found that fish release started at least in 1980-1990s in Yushu. Tibetan residents released fish in large amounts and released fish were usually exotic commercial fish purchased from market. Despite such long-term and intensive fish release activities, released fish were few in local rivers. On the other hand, Eurasian otters mainly prey on fish and released fish accounted for ~20% of relative read abundance of prey DNA in otters' diet, indicating their high preference on released fish. Our study suggested that religious fish release may provide additional food resources for otters, whereas otters, as a top predator in local rivers, may deplete non-native fish once they were released and, therefore, reduce the probability of colonization of released fish, although further studies are required to assess otters' impact. Our study revealed otters' diet in Yushu, providing basic information for local otter management and conservation. Furthermore, it represents a case showing that native predators prey on religious released animals, implying a probable direction for controlling invasive species through native predator conservation.

A new, effective method for diagnosing GLAD lesions: the chicken-wing muscle up test.

PURPOSE: We aimed to develop and evaluate a new diagnostic method, the 'chicken-wing muscle up test', to improve the accuracy of diagnosis of glenolabral articular disruption (GLAD) lesions compared to currently used clinical tests for injuries to the labrum. METHODS: Preoperative evaluations were conducted on 85 patients undergoing arthroscopic surgery at a single center between July 2021 to July 2022. The diagnostic performance of the preoperative clinical examinations (chicken-wing muscle up test, O'Brien test, crank test, and O'Driscoll test) were validated against the findings of arthroscopic examinations. RESULTS: 12 of the 85 patients in this study had arthroscopically confirmed GLAD lesions. The chicken-wing muscle up test demonstrated significantly higher sensitivity (83.33%) for GLAD lesions than the O'Brien test (33.33%), but not the crank test (50.00%) or O'Driscoll test (25.00%), and significantly higher specificity (95.89%) than the O'Brien test (75.34%), crank test (82.19%), and O'Driscoll test (71.23%). The chicken-wing muscle up test had the largest area under the receiver operating characteristic curve (AUC = 0.896, P < 0.001; O'Driscoll test AUC = 0.543, P > 0.05; crank test AUC = 0.661, P > 0.05; O'Brien test AUC = 0.481, P > 0.05), indicating significantly better diagnostic efficacy for GLAD lesions than the other three tests. CONCLUSIONS: The chicken-wing muscle up test is a reliable diagnostic method that improves the accuracy of diagnosis of GLAD lesions.

Widely Targeted Metabolomics Provides New Insights into Nutritional Profiling and Reveals the Flavonoid Pathway of Pea (Pisum sativum L.).

To learn more about the nutritional composition and health benefits for human consumers of peas, we used a widely targeted metabolomics-based approach to reveal the metabolite components from three main varieties, and a total of 1095 metabolites were identified. A comparison of 487 differentially accumulated metabolites shared among three varieties of fresh and dried peas found most of the amino acids and derivatives were downregulated and most of the lipids and flavonoids were upregulated in dried peas. Furthermore, comparing the main nutrient profiles exclusively showed that there were few differences in free fatty acids, sugars, vitamins, and alkaloids between dried and fresh peas. Peas are especially enriched with B-group vitamins. Through detailed identification and classification, the flavonoid pathway of peas was revealed; a variety of glycosylated derivatives from kaempferol, quercetin, and luteolin were confirmed to be abundant in peas. It was also found that isoflavones are richer in peas than in many other plants, and putatively the isoflavone synthesis pathway originates from liquiritigenin and naringenin. Our study not only offers guidance for understanding the nutritional components of peas, but also provides the basis for healthy diet analysis of the edible value and health benefits of peas.

Leucine Supplementation Modulates Lipid Metabolism and Inflammation in Early Weaning Piglets.

Early weaning can induce the programmed dysregulation of glycolipid metabolism and inflammation in adult animals. The primary objective of this study was to evaluate the efficacy of leucine supplementation administered promptly after early weaning in mitigating these adverse effects in piglets. At day 21, 24 piglets were randomly selected and divided into 3 groups: EW group where the piglets were weaned at day 21 and fed basal diet, EWL group where the piglets were weaned at day 21 and fed the basal diet with supplementation of 1% leucine, and C group where the piglets were fed basal diet and weaned at 28 days. Each group contained eight replicates, with one piglet per replicate. The results indicated that early weaning had an impact on gut health and could activate the inhibitor of the kappa B kinase gamma/inhibitor kappa B alpha/NF-kappa-B (IKKγ/IκBα/NF-κB) signaling pathway to ameliorate pro-inflammatory factor and apoptosis levels. Furthermore, early weaning reduced the activity of fatty acid ß oxidation (FAßO) and affected genes linked with lipid metabolism. Supplementing with leucine can improve the effects of these factors. In summary, leucine may alleviate the influences of early weaning on the lipid metabolism and inflammation in piglets.

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.

Health insurance coverage among incident cancer cases from population-based cancer registries in 49 US states, 2010-2019.

Having health insurance coverage is a strong determinant of cancer care access and survival in the United States. The expansion of Medicaid income eligibility under the Affordable Care Act has increased insurance coverage for working-age adults. Using data from the Cancer Incidence in North America (CiNA) in 2010-2019, we identified 6 432 117 incident cancer cases with known insurance status diagnosed at age 18-64 years from population-based registries of 49 states. Considerable variation in Medicaid coverage and uninsured rate exists across states, especially by Medicaid expansion status. Among expansion states, Medicaid coverage increased from 14.1% in 2010 to 19.9% in 2019, while the Medicaid coverage rate remained lower (range = 11.7% - 12.7%) in non-expansion states. The uninsured rate decreased from 4.9% to 2.1% in expansion states, while in non-expansion states, the uninsured rate decreased slightly from 9.5% to 8.1%. In 2019, 111 393 cancer cases (16.9%) had Medicaid coverage at diagnosis (range = 7.6%-37.9% across states), and 48 357 (4.4%) were uninsured (range = 0.5%-13.2%). These estimates suggest that many patients with cancer may face challenges with care access and continuity, especially following the unwinding of COVID-19 pandemic protections for Medicaid coverage. State cancer prevention and control efforts are needed to mitigate cancer care disparities among vulnerable populations.

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.

Preserving shape details of pulse signals for video-based blood pressure estimation.

In recent years, imaging photoplethysmograph (iPPG) pulse signals have been widely used in the research of non-contact blood pressure (BP) estimation, in which BP estimation based on pulse features is the main research direction. Pulse features are directly related to the shape of pulse signals while iPPG pulse signals are easily disturbed during the extraction process. To mitigate the impact of pulse feature distortion on BP estimation, it is necessary to eliminate interference while retaining valuable shape details in the iPPG pulse signal. Contact photoplethysmograph (cPPG) pulse signals measured at rest can be considered as the undisturbed reference signal. Transforming the iPPG pulse signal to the corresponding cPPG pulse signal is a method to ensure the effectiveness of shape details. However, achieving the required shape accuracy through direct transformation from iPPG to the corresponding cPPG pulse signals is challenging. We propose a method to mitigate this challenge by replacing the reference signal with an average cardiac cycle (ACC) signal, which can approximately represent the shape information of all cardiac cycles in a short time. A neural network using multi-scale convolution and self-attention mechanisms is developed for this transformation. Our method demonstrates a significant improvement in the maximal information coefficient (MIC) between pulse features and BP values, indicating a stronger correlation. Moreover, pulse signals transformed by our method exhibit enhanced performance in BP estimation using different model types. Experiments are conducted on a real-world database with 491 subjects in the hospital, averaging 60 years of age.

Mental Health Care Utilization Among Parents of Children With Cancer.

Importance: Caring for children diagnosed with cancer may adversely affect the mental health (MH) of parents. Objective: To characterize utilization of MH services among parents of children with vs without cancer using nationwide commercial claims data. Design, Setting, and Participants: For this cross-sectional study, the Merative MarketScan Commercial Claims Database was used to identify continuously insured families of children treated for cancer (aged ≤21 years at diagnosis) during 2010 to 2018, compared with families who matched eligibility criteria but did not have a child with a cancer history. Parents were assessed from 18 months before to 12 months after their child's cancer diagnosis. Analyses were conducted from February 2022 to September 2023. Exposures: Children's cancer diagnosis. Main Outcomes and Measures: Outcomes included parents' MH-related visits during the first year following their child's cancer diagnosis. Logistic regressions compared outcomes between families of children with vs without cancer, adjusting for sociodemographic and clinical factors. Results: This study included 4837 families of children with cancer (4210 mothers and 4016 fathers) and 24 185 families of children without cancer (21 444 mothers and 19 591 fathers) with continuous insurance enrollment. Most household leads were aged 35 to 54 years (3700 [76.5%] in families of children with cancer vs 17 812 [73.6%] in families of children without cancer) and resided in urban areas (4252 [87.9%] vs 21 156 [87.5%]). The probabilities of parents having anxiety-related visits (10.6% vs 7.0%), depression-related visits (8.4% vs 6.1%), and any MH-related visits (18.1% vs 13.3%) were higher in families of children with vs without cancer. Adjusted analyses showed absolute increases of 3.2 percentage points (95% CI, 2.3 to 4.0; 45.7% relative increase), 2.2 percentage points (95% CI, 1.4 to 3.0; 36.1% relative increase), and 4.2 percentage points (95% CI, 3.1 to 5.3; 31.3% relative increase) in the probabilities of 1 or both parents having anxiety-related visits, depression-related visits, and any MH-related visits, respectively, among families of children with vs without cancer. Such differences were greater in magnitude among mothers than fathers. Conclusions and Relevance: In this cohort study of privately insured parents, those caring for children with cancer had a higher likelihood of utilizing MH care than other parents. These findings underline the importance of interventions toward targeted counseling and support to better meet MH care needs among parents and caregivers of children with cancer.

Associations of Medical Debt With Health Status, Premature Death, and Mortality in the US.

Importance: Medical debt is increasingly common in the US. Little is known regarding its association with population health. Objective: To examine the associations of medical debt with health status, premature death, and mortality at the county level in the US. Design, Setting, and Participants: This cross-sectional study was conducted at the US county level using 2018 medical debt data from the Urban Institute Debt in America project linked with 2018 data on self-reported health status and premature death from the County Health Rankings & Roadmaps and with 2015 to 2019 mortality data from the National Center for Health Statistics. Data analysis was performed from August 2022 to May 2023. Exposure: Share of population with any medical debt in collections and median amount of medical debt. Main Outcomes and Measures: Health status was measured as (1) the mean number of physically and mentally unhealthy days in the past 30 days per 1000 people, (2) the mean number of premature deaths measured as years of life lost before age 75 years per 1000 people, and (3) age-adjusted all-cause and 18 cause-specific mortality rates (eg, malignant cancers, heart disease, and suicide) per 100 000 person-years. Multivariable linear models were fitted to estimate the associations between medical debt and health outcomes. Results: A total of 2943 counties were included in this analysis. The median percentage of the county population aged 65 years or older was 18.3% (IQR, 15.8%-20.9%). Across counties, a median 3.0% (IQR, 1.2%-11.9%) of the population were Black residents, 4.3% (IQR, 2.3%-9.7%) were Hispanic residents, and 84.5% (IQR, 65.7%-93.3%) were White residents. On average, 19.8% (range, 0%-53.6%) of the population had medical debt. After adjusting for county-level sociodemographic characteristics, a 1-percentage point increase in the population with medical debt was associated with 18.3 (95% CI, 16.3-20.2) more physically unhealthy days and 17.9 (95% CI, 16.1-19.8) more mentally unhealthy days per 1000 people during the past month, 1.12 (95% CI, 1.03-1.21) years of life lost per 1000 people, and an increase of 7.51 (95% CI, 6.99-8.04) per 100 000 person-years in age-adjusted all-cause mortality rate. Associations of medical debt and elevated mortality rates were consistent for all leading causes of death, including cancer (1.12 [95% CI, 1.02-1.22]), heart disease (1.39 [95% CI, 1.21-1.57]), and suicide (0.09 [95% CI, 0.06-0.11]) per 100 000 person-years. Similar patterns were observed for associations between the median amount of medical debt and the aforementioned health outcomes. Conclusions and Relevance: These findings suggest that medical debt is associated with worse health status, more premature deaths, and higher mortality rates at the county level in the US. Therefore, policies increasing access to affordable health care, such as expanding health insurance coverage, may improve population health.

US Medicare Hospice and Palliative Medicine Physician Workforce and Service Delivery in 2008-2020.

CONTEXT: Despite clinical benefits of early palliative care, little is known about Medicare physician workforce specialized in Hospice and Palliative Medicine (HPM) and their service delivery settings. OBJECTIVES: To examine changes in Medicare HPM physician workforce and their service delivery settings in 2008-2020. METHODS: Using the Medicare Data on Provider Practice and Specialty from 2008 to 2020, we identified 2375 unique Medicare Fee-For-Service (FFS) physicians (15,565 physician-year observations) with self-reported specialty in "Palliative Care and Hospice". We examined changes in the annual number of HPM physicians, average number of Medicare services overall and by care setting, total number of Medicare FFS beneficiaries, and total Medicare allowed charges billed by the physician. RESULTS: The number of Medicare HPM physicians increased 2.32 times from 771 in 2008 to 1790 in 2020. The percent of HPM physicians practicing in metropolitan areas increased from 90% to 96% in 2008-2020. Faster growth was also observed in female physicians (52.4% to 60.1%). Between 2008 and 2020, we observed decreased average annual Medicare FFS beneficiaries (170 to 123), number of FFS services (467 to 335), and Medicare allowed charges billed by the physician ($47,230 to $37,323). The share of palliative care delivered in inpatient settings increased from 47% to 68% in 2008-2020; whereas the share of services delivered in outpatient settings decreased from 37% to 19%. CONCLUSION: Despite growth in Medicare HPM physician workforce, access is disproportionately concentrated in metropolitan and inpatient settings. This may limit receipt of early outpatient specialized palliative care, especially in nonmetropolitan areas.

Isobaric Tags for Relative and Absolute Quantitation-Based Proteomics Analysis Revealed Proteins Involved in Drought Response during the Germination Stage in Faba Bean.

The faba bean, a significant cool-season edible legume crop, is susceptible to drought during the germination stage. Research regarding the genetic regulation of drought tolerance throughout this stage in the faba bean is limited. The differentially expressed proteins (DEPs) in faba beans between the drought-tolerant variety C105 and the drought-sensitive variant E1 during seed germination were identified in this work, accomplished through isobaric tags for relative and absolute quantitation (iTRAQ) analysis. A total of 3827 proteins were identified in the two varieties of germinating seeds. Compared to those of variety E1, an increase in 108 DEPs and a decrease in 61 DEPs were observed in variety C105 under drought. Conversely, in the control group, variety C105 showed 108 significantly upregulated DEPs and 55 significantly downregulated DEPs. GO and KEGG analyses showed that the DEPs associated with glutathione metabolism and protein processing demonstrated significant increases in response to drought stress. Protein-protein interaction (PPI) analysis unveiled three closely connected functional modules of protein translation, DNA replication, and post-translational modification, originating from 22 DEPs derived from the germination period of two varieties under drought stress. To verify the proteomic function, we selected three differentially expressed protein coding genes, which were overexpressed or silenced in tobacco, thereby enhancing the drought resistance of tobacco. This was accompanied via altered levels of superoxide dismutase or peroxidase in transgenic plants under drought stress. The possible mechanism for drought tolerance in germinating seeds of faba bean involves increasing protein translation, decreasing DNA replication, and modifying chromatin. These findings offer invaluable insights into the reaction mechanism in response to drought stress in faba beans. The identified DEPs could be utilized in faba bean breeding initiatives to manage drought.

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.

Hypoxic bone marrow mesenchymal stem cell exosomes promote angiogenesis and enhance endometrial injury repair through the miR-424-5p-mediated DLL4/Notch signaling pathway.

Background: Currently, bone marrow mesenchymal stem cells (BMSCs) have been reported to promote endometrial regeneration in rat models of mechanically injury-induced uterine adhesions (IUAs), but the therapeutic effects and mechanisms of hypoxic BMSC-derived exosomes on IUAs have not been elucidated. Objective: To investigate the potential mechanism by which the BMSCS-derived exosomal miR-424-5p regulates IUA angiogenesis through the DLL4/Notch signaling pathway under hypoxic conditions and promotes endometrial injury repair. Methods: The morphology of the exosomes was observed via transmission electron microscopy, and the expression of exosome markers (CD9, CD63, CD81, and HSP70) was detected via flow cytometry and Western blotting. The expression of angiogenesis-related genes (Ang1, Flk1, Vash1, and TSP1) was detected via RT‒qPCR, and the expression of DLL4/Notch signaling pathway-related proteins (DLL4, Notch1, and Notch2) was detected via Western blotting. Cell proliferation was detected by a CCK-8 assay, and angiogenesis was assessed via an angiogenesis assay. The expression of CD3 was detected by immunofluorescence. The endometrial lesions of IUA rats were observed via HE staining, and the expression of CD3 and VEGFA was detected via immunohistochemistry. Results: Compared with those in exosomes from normoxic conditions, miR-424-5p was more highly expressed in the exosomes from hypoxic BMSCs. Compared with those in normoxic BMSC-derived exosomes, the proliferation and angiogenesis of HUVECs were significantly enhanced after treatment with hypoxic BMSC-derived exosomes, and these effects were weakened after inhibition of miR-424-5p. miR-424-5p can target and negatively regulate the expression of DLL4, promote the expression of the proangiogenic genes Ang1 and Flk1, and inhibit the expression of the antiangiogenic genes Vash1 and TSP1. The effect of miR-424-5p can be reversed by overexpression of DLL4. In IUA rats, treatment with hypoxic BMSC exosomes and the miR-424-5p mimic promoted angiogenesis and improved endometrial damage. Conclusion: The hypoxic BMSC-derived exosomal miR-424-5p promoted angiogenesis and improved endometrial injury repair by regulating the DLL4/Notch signaling pathway, which provides a new idea for the treatment of IUAs.