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Background: Dupilumab is an mAb that has been shown to decrease symptoms and severity of atopic dermatitis (AD). It was approved for use in adolescents and children in a stepwise manner from 2019 to 2022. Racial and ethnic disparities have been described in access to emerging therapies in many conditions, including treatment with dupilumab for AD in adult patients. Objective: We sought to assess racial and ethnic disparities in moderate to severe AD treatment with dupilumab in the pediatric population. Methods: This retrospective study identified 12,918 patients with AD aged 0 to 17 years who had at least a 6-month follow-up period between January 2020 and September 2023. The primary end point of dupilumab prescription was compared between racial and ethnic groups and a reference group of non-Hispanic White patients while adjusting for confounders. Results: Among the patients, 18.1% were Black, 40.5% Hispanic, 28.9% non-Hispanic White, and 12.4% Other race. Black (odds ratio, 0.43; P = .006) and Hispanic (odds ratio, 0.46; P < .001) patients had significantly lower odds of receiving dupilumab compared with the reference group. Conclusions: This study may indicate a racial and ethnic disparity negatively affecting access to treatment with dupilumab for Black and Hispanic children and adolescents with AD. Because previous studies have not indicated decreased severity of AD in these patient populations, less frequent use is likely due to other underlying factors such as differential access to care, cultural differences, language barriers, and socioeconomic factors. The contributing factors must be further identified and addressed to ensure health equity in pediatric AD.

Introduction: The scarcity of available organs for kidney transplantation has resulted in a substantial waiting time for patients with end-stage kidney disease. This prolonged wait contributes to an increased risk of cardiovascular mortality. Calcification of large arteries is a high-risk factor in the development of cardiovascular diseases, and it is common among candidates for kidney transplant. The aim of this study was to correlate abdominal arterial calcification (AAC) score value with mortality on the waitlist. Methods: We modified the coronary calcium score and used it to quantitate the AAC. We conducted a retrospective clinical study of all adult patients who were listed for kidney transplant, between 2005 and 2015, and had abdominal computed tomography scan. Patients were divided into two groups: those who died on the waiting list group and those who survived on the waiting list group. Results: Each 1,000 increase in the AAC score value of the sum score of the abdominal aorta, bilateral common iliac, bilateral external iliac, and bilateral internal iliac was associated with increased risk of death (HR 1.034, 95% CI: 1.013, 1.055) (p = 0.001). This association remained significant even after adjusting for various patient characteristics, including age, tobacco use, diabetes, coronary artery disease, and dialysis status. Conclusion: The study highlights the potential value of the AAC score as a noninvasive imaging biomarker for kidney transplant waitlist patients. Incorporating the AAC scoring system into routine imaging reports could facilitate improved risk assessment and personalized care for kidney transplant candidates.

BackgroundWearable physiological monitoring devices are promising tools for remote monitoring and early detection of potential health changes of interest. The widespread adoption of such an approach across communities and over long periods of time will require an automated data platform for collecting, processing, and analyzing relevant health information. ObjectiveIn this study, we explore prospective monitoring of individual health through an automated data collection, metrics extraction, and health anomaly analysis pipeline in free-living conditions over a continuous monitoring period of several months with a focus on viral respiratory infections, such as influenza or COVID-19. MethodsA total of 59 participants provided smartwatch data and health symptom and illness reports daily over an 8-month window. Physiological and activity data from photoplethysmography sensors, including high-resolution interbeat interval (IBI) and step counts, were uploaded directly from Garmin Fenix 6 smartwatches and processed automatically in the cloud using a stand-alone, open-source analytical engine. Health risk scores were computed based on a deviation in heart rate and heart rate variability metrics from each individual’s activity-matched baseline values, and scores exceeding a predefined threshold were checked for corresponding symptoms or illness reports. Conversely, reports of viral respiratory illnesses in health survey responses were also checked for corresponding changes in health risk scores to qualitatively assess the risk score as an indicator of acute respiratory health anomalies. ResultsThe median average percentage of sensor data provided per day indicating smartwatch wear compliance was 70%, and survey responses indicating health reporting compliance was 46%. A total of 29 elevated health risk scores were detected, of which 12 (41%) had concurrent survey data and indicated a health symptom or illness. A total of 21 influenza or COVID-19 illnesses were reported by study participants; 9 (43%) of these reports had concurrent smartwatch data, of which 6 (67%) had an increase in health risk score. ConclusionsWe demonstrate a protocol for data collection, extraction of heart rate and heart rate variability metrics, and prospective analysis that is compatible with near real-time health assessment using wearable sensors for continuous monitoring. The modular platform for data collection and analysis allows for a choice of different wearable sensors and algorithms. Here, we demonstrate its implementation in the collection of high-fidelity IBI data from Garmin Fenix 6 smartwatches worn by individuals in free-living conditions, and the prospective, near real-time analysis of the data, culminating in the calculation of health risk scores. To our knowledge, this study demonstrates for the first time the feasibility of measuring high-resolution heart IBI and step count using smartwatches in near real time for respiratory illness detection over a long-term monitoring period in free-living conditions.

Objective: There is emerging evidence suggesting that pregnancy loss (induced or natural) is associated with an increased risk of cardiovascular diseases (CVD). This prospective longitudinal study investigates the effect of prior pregnancy losses on CVD risk during the first six months following a first live birth. Methods: Medicaid claims of 1,002,556 low-income women were examined to identify history of pregnancy losses, CVD, diabetes, and hyperlipidemia prior to first live birth. The study population was categorized into five groups: A: women with no pregnancy loss or CVD history prior to first live birth; B: women with pregnancy loss and no CVD prior to first live birth. C: women with a first CVD diagnosis after a first pregnancy ending in a loss and before their first live birth. D: women with CVD prior to first live birth and no history of pregnancy loss. E: women with both CVD and pregnancy loss prior to their first live birth. Results: After controlling for age, race, state of residence, and history of diabetes and hyperlipidemia, the risk of CVD in the six-month period following a first live birth were 15%, 214%, 79% and 129% more common for Groups B, C, D and E, respectively, compared to Group A. Conclusions: Pregnancy loss is an independent risk factor for CVD risk following a first live birth, both for women with and without a prior history of CVD. The risk is highest when CVD is first diagnosed after a pregnancy loss and prior to a first live birth.

Abstract Alzheimer’s disease (AD), characterized by the deposition of amyloid-β (Aβ) in senile plaques and neurofibrillary tangles of phosphorylated tau (pTau), is increasingly recognized as a complex disease with multiple pathologies. AD sometimes pathologically overlaps with age-related tauopathies such as four repeat (4R)-tau predominant argyrophilic grain disease (AGD). While AGD is often detected with AD pathology, the contribution of APOE4 to AGD risk is not clear despite its robust effects on AD pathogenesis. Specifically, how APOE genotype influences Aβ and tau pathology in co-occurring AGD and AD has not been fully understood. Using postmortem brain samples (N = 353) from a neuropathologically defined cohort comprising of cases with AD and/or AGD pathology built to best represent different APOE genotypes, we measured the amounts of major AD-related molecules, including Aβ40, Aβ42, apolipoprotein E (apoE), total tau (tTau), and pTau181, in the temporal cortex. The presence of tau lesions characteristic of AD (AD-tau) was correlated with cognitive decline based on Mini-Mental State Examination (MMSE) scores, while the presence of AGD tau lesions (AGD-tau) was not. Interestingly, while APOE4 increased the risk of AD-tau pathology, it did not increase the risk of AGD-tau pathology. Although APOE4 was significantly associated with higher levels of insoluble Aβ40, Aβ42, apoE, and pTau181, the APOE4 effect was no longer detected in the presence of AGD-tau. We also found that co-occurrence of AGD with AD was associated with lower insoluble Aβ42 and pTau181 levels. Overall, our findings suggest that different patterns of Aβ, tau, and apoE accumulation mediate the development of AD-tau and AGD-tau pathology, which is affected by APOE genotype.

Introduction: Urinary tract infections (UTI) are one of the most common infections encountered in the emergency department (ED) with an estimated 2-3 million annual visits.  Commonly prescribed antibiotics for UTIs have shown growing rates of resistance.  Previous studies lack direction on improving UTI treatment based on the labs available to the bedside clinician.   Methods: We sought to determine if antibiotic resistance in UTIs was related to demographics, urinalysis, and history of renal failure or kidney stones. We conducted an analysis of 892 women ≥18 years of age discharged from the ED with a UTI diagnosis. We assessed predictors of nitrofurantoin resistance, cefazolin resistance, ciprofloxacin resistance, and trimethoprim-sulfamethoxazole resistance using unadjusted and multivariable logistic regression models. Results: Antibiotic resistance was 13.6% for nitrofurantoin, 11.9% for cefazolin, 12.8% for ciprofloxacin, and 17.1% for trimethoprim-sulfamethoxazole. In multivariable analysis, significant independent associations with an increased likelihood of resistance to nitrofurantoin were observed for less urine blood (OR [per 1 category increase of score] 0.81; P = 0.02); greater mucous (OR [per 1 category increase of score] 1.22; P = 0.02); less specific gravity urine (OR [per 1 category increase] 0.87; P = 0.04), and presence of any history of kidney stones (OR 3.24; P = 0.01). There were no significant predictors for cefazolin resistance (all P ≥0.06); age was the only significant predictor of ciprofloxacin resistance (OR per 10 year increase] 1.10, P = 0.05), and lower specific gravity urine was significantly associated with an increased risk of resistance to trimethoprim- sulfamethoxazole (OR [per 1 category increase] 0.88, P = 0.04). Conclusion: Women with any history of kidney stones may have bacteriuria resistant to nitrofurantoin, suggesting that providers might consider alternative antibiotic therapies in this scenario.

While there is clear evidence to suggest poorer outcome associated with multi-hit (MH) TP53 mutation compared to single-hit (SH) in lower-risk myelodysplastic syndrome (MDS), data are conflicting in both higher-risk MDS and acute myeloid leukemia (AML). We conducted an indepth analysis utilizing data from 10 US academic institutions to study differences in molecular characteristics and outcomes of SH (n= 139) versus MH (n= 243) TP53MTAML. Complex cytogenetics (CG) were more common in MH compared to SH TP53MT AML (p

IntroductionThe NIH All of Us Research Program will have the scale and scope to enable research for a wide range of diseases, including cancer. The program's focus on diversity and inclusion promises a better understanding of the unequal burden of cancer. Preliminary cancer ascertainment in the All of Us cohort from two data sources (self-reported versus electronic health records (EHR)) is considered.Materials and methodsThis work was performed on data collected from the All of Us Research Program's 315,297 enrolled participants to date using the Researcher Workbench, where approved researchers can access and analyze All of Us data on cancer and other diseases. Cancer case ascertainment was performed using data from EHR and self-reported surveys across key factors. Distribution of cancer types and concordance of data sources by cancer site and demographics is analyzed.Results and discussionData collected from 315,297 participants resulted in 13,298 cancer cases detected in the survey (in 89,261 participants), 23,520 cancer cases detected in the EHR (in 203,813 participants), and 7,123 cancer cases detected across both sources (in 62,497 participants). Key differences in survey completion by race/ethnicity impacted the makeup of cohorts when compared to cancer in the EHR and national NCI SEER data.ConclusionsThis study provides key insight into cancer detection in the All of Us Research Program and points to the existing strengths and limitations of All of Us as a platform for cancer research now and in the future.

Greenhouse production of high-quality young annual bedding plants (plugs) at northern latitudes often requires supplemental lighting to compensate for a low natural daily light integral (DLI), but radiation interception by plugs is limited by a low leaf area index. Some species show an increase in leaf area in response to growth under a low ratio of red to far-red radiation (R:FR), and an early increase in leaf area may allow for more effective radiation capture by seedlings and a reduction in wasted radiation. Thus, the objective of this study was to examine the effects of end-of-day far-red (EOD-FR) radiation treatments varying in intensity, R:FR (600–700 nm/700–780 nm), and duration on early leaf expansion and plug quality for petunia (Petunia ×hybrida) ‘Wave Purple’ and ‘Dreams Midnight’. Seedlings were grown in 128-cell trays in a common greenhouse environment under a simulated winter DLI (∼5.3 mol·m−2·s−1) and received one of four EOD-FR treatments, control conditions (no EOD-FR or supplemental lighting), or supplemental lighting (target photosynthetic photon flux density of 70 μmol·m−2·s−1). The EOD-FR treatments were provided for 3 weeks on cotyledon emergence and included the following: 10 μmol·m−2·s−1 of far-red radiation for 30 minutes with a R:FR of ∼0.8 (EODFL), 10 or 20 μmol·m−2·s−1 of far-red radiation for 30 minutes with a R:FR of ∼0.15 (EOD10:30 and EOD20:30, respectively), or 20 μmol·m−2·s−1 of far-red radiation for 240 minutes with a R:FR of ∼0.15 (EOD20:240). Destructive data were collected 14 and 21 days after cotyledon emergence. Seedlings that received EOD-FR treatments did not show any increase in leaf area compared with control or supplemental lighting treatments. Stem length generally increased under EOD-FR treatments compared with supplemental lighting and control treatments; greater elongation was observed when the R:FR decreased from 0.8 to 0.15, and when treatment duration increased from 30 minutes to 240 minutes. However, at a R:FR of 0.15 and a treatment duration of 30 minutes, an increase in far-red radiation intensity from 10 to 20 μmol·m−2·s−1 did not promote further stem elongation resulting in similar stem lengths for both cultivars under EOD10:30 and EOD20:30. Results of this study indicate that under low DLIs, EOD-FR radiation applied in the first 3 weeks of seedling production does not promote early leaf area expansion, and generally decreases seedling quality for petunia. As responses to far-red radiation may vary based on study taxa, incident radiation, and DLI, future research examining EOD-FR–induced morphological changes is warranted.

James Studnicki,1 Tessa Longbons,1 John Fisher,1 David C Reardon,2 Ingrid Skop,1 Christina A Cirucci,1 Donna J Harrison,3 Christopher Craver,1 Maka Tsulukidze,4 Zbigniew Ras5 1Charlotte Lozier Institute, Arlington, VA, USA; 2Elliot Institute, Springfield, IL, USA; 3American Association of Pro-Life Obstetricians and Gynecologists, Eau Claire, MI, USA; 4Department of Health Sciences, Florida Gulf Coast University, Fort Myers, FL, USA; 5Computer Science Department, University of North Carolina at Charlotte, Charlotte, NC, USACorrespondence: Tessa Longbons, Charlotte Lozier Institute, 2776 S. Arlington Mill Drive, PO Box 803, Arlington, VA, 22206, USA, Tel +1 202 223 8073, Email tlongbons@lozierinstitute.orgObjective: To determine whether exposure to a first pregnancy outcome of induced abortion, compared to a live birth, is associated with an increased risk and likelihood of mental health morbidity.Materials and methods: Participants were continuously eligible Medicaid beneficiaries age 16 in 1999, and assigned to either of two cohorts based upon the first pregnancy outcome, abortion (n = 1331) or birth (n = 3517), and followed through to 2015. Outcomes were mental health outpatient visits, inpatient hospital admissions, and hospital days of stay. Exposure periods before and after the first pregnancy outcome, a total of 17 years, were determined for each cohort.Findings: Women with first pregnancy abortions, compared to women with births, had higher risk and likelihood of experiencing all three mental health outcome events in the transition from pre- to post-pregnancy outcome periods: outpatient visits (RR 2.10, CL 2.08– 2.12 and OR 3.36, CL 3.29– 3.42); hospital inpatient admissions (RR 2.75, CL 2.38– 3.18 and OR 5.67, CL 4.39– 7.32); hospital inpatient days of stay (RR 7.38, CL 6.83– 7.97 and OR 19.64, CL 17.70– 21.78). On average, abortion cohort women experienced shorter exposure time before (6.43 versus 7.80 years), and longer exposure time after (10.57 versus 9.20 years) the first pregnancy outcome than birth cohort women. Utilization rates before the first pregnancy outcome, for all three utilization events, were higher for the birth cohort than for the abortion cohort.Conclusion: A first pregnancy abortion, compared to a birth, is associated with significantly higher subsequent mental health services utilization following the first pregnancy outcome. The risk attributable to abortion is notably higher for inpatient than outpatient mental health services. Higher mental health utilization before the first pregnancy outcome for birth cohort women challenges the explanation that pre-existing mental health history explains mental health problems following abortion, rather than the abortion itself.Keywords: abortion, mental health, inpatient mental health utilization, outpatient mental health utilization, repeat abortion

Electric lighting is often necessary to achieve a target daily light integral (DLI) for the production of high-quality young annual bedding plants (plugs). Early in production, plugs have a low leaf area index that limits light interception and likely results in wasted radiation supplied by electric sources. Previous research has shown that the addition of far-red radiation (700–780 nm) to the radiation spectrum in sole-source lighting experiments or the use of end-of-day far-red (EOD-FR) radiation treatments can promote an increase in leaf expansion and leaf area for many species. However, leaf expansion in response to far-red radiation may depend on other factors such as the ratio of red (600–699 nm) to far-red radiation (R:FR) and air temperature. Thus, the objectives of this work were to examine the effects of far-red radiation applied throughout the photoperiod and as an end-of-day radiation treatment on the morphology of petunia ‘Dreams Midnight’ seedlings grown under different temperature conditions. Specifically, petunia seed was sown in 128-cell trays and moved to one of two growth chambers set at 16 or 21 °C when cotyledons unfolded. Seedlings received an equal total photon flux density (400–780 nm) of 164 µmol·m−2·s−1 for a 17.25-hour photoperiod, and either a high (∼10.7) or low R:FR (0.5). Low R:FR-treated seedlings were grown at a constant temperature of either 16 or 21 °C and placed under blackout conditions at the end of the photoperiod. High R:FR-grown seedlings received either a 1-hour end-of-day white (EOD-W) or EOD-FR treatment at the end of the photoperiod, and were grown at a constant 16 or 21 °C; one EOD-FR treatment was also shifted from the 21 °C chamber to the 16 °C at the end of the photoperiod for both the EOD-FR treatment and subsequent dark period. Seedlings were harvested at 21 and 28 days after treatment initiation. For petunia seedlings grown at 21 °C, EOD-FR treatments had minimal effect on morphology or dry mass as all measured parameters, including total and average leaf area and stem length, were similar to EOD-W treatments. In contrast, low R:FR-treated seedlings showed responses characteristic of plants grown under shade, including significant stem elongation, an increase in total and average leaf area, and a reduction in leaf mass per unit area. As expected, production at 16 °C slowed the growth of petunia seedlings resulting in much smaller plants compared with the 21 °C grown plants, but shade responses such as elongated leaves and stems under a low R:FR were apparent. The EOD-FR–treated seedlings that received the diurnal temperature shift also showed reduced leaf area and dry mass compared with their constant 21 °C counterparts. Shade responses were observable at both 16 and 21 °C for low R:FR-grown plants, but the quantifiable impact of temperature on far-red responses could not be fully determined in the present study. Further research is warranted investigating crop responses to far-red radiation as well as potential interacting environmental factors as the promotion of morphological responses, such as leaf expansion, early in production may prove a useful strategy.

Introduction: Meningitis is a serious and potentially life-threatening infection of the central nervous system. Cryptococcus neoformans is a rare fungal cause of meningitis that commonly presents with atypical symptoms. Although this infection is most common in immunocompromised patients, it also occurs in immunocompetent patients. This case report describes an atypical presentation of cryptococcal meningitis in a seemingly immunocompetent patient.Case Report: A 40-year-old immunocompetent patient with no significant past medical history had visited the emergency department (ED) five times within a span of 30 days reporting dental pain and headache. Throughout each of the visits, no clear symptoms signaling the need for a meningitis workup were observed, as the patient had been afebrile, displayed no nuchal rigidity, and his presenting symptoms subsided within the ED after treatment. A lumbar puncture was performed after emergency medical services brought the patient in for his sixth ED visit, initially for stroke-like symptoms and altered mental status. Spinal fluid was indicative of cryptococcal meningitis.Conclusion: This case highlights the challenge of identifying cryptococcal meningitis in the ED, particularly in immunocompetent patients who do not display classic meningitis symptoms. It also highlights the importance of keeping a broad differential and carefully ruling out diagnoses when patients return to the ED multiple times for the same complaint.

BackgroundEvasion from programmed cell death is a hallmark of cancer and can be achieved in cancer cells by overexpression of inhibitor of apoptosis proteins (IAPs). Second mitochondria-derived activator of caspases (SMAC) directly bind to IAPs and promote apoptosis; thus, SMAC mimetics have been investigated in a variety of cancer types. particularly in diseases with high inflammation and NFĸB activation. Given that elevated TNFα levels and NFĸB activation is a characteristic feature of myeloproliferative neoplasms (MPN), we investigated the effect of the SMAC mimetic LCL-161 on MPN cell survival in vitro and disease development in vivo.MethodsTo investigate the effect of the SMAC mimetic LCL-161 in vitro, we utilized murine and human cell lines to perform cell viability assays as well as primary bone marrow from mice or humans with JAK2V617F-driven MPN to interrogate myeloid colony formation. To elucidate the effect of the SMAC mimetic LCL-161 in vivo, we treated a JAK2V617F-driven mouse model of MPN with LCL-161 then assessed blood counts, splenomegaly, and myelofibrosis.ResultsWe found that JAK2V617F-mutated cells are hypersensitive to the SMAC mimetic LCL-161 in the absence of exogenous TNFα. JAK2 kinase activity and NFĸB activation is required for JAK2V617F-mediated sensitivity to LCL-161, as JAK or NFĸB inhibitors diminished the differential sensitivity of JAK2V617F mutant cells to IAP inhibition. Finally, LCL-161 reduces splenomegaly and may reduce fibrosis in a mouse model of JAK2V617F-driven MPN.ConclusionLCL-161 may be therapeutically useful in MPN, in particular when exogenous TNFα signaling is blocked. NFĸB activation is a characteristic feature of JAK2V617F mutant cells and this sensitizes them to SMAC mimetic induced killing even in the absence of TNFα. However, when exogenous TNFα is added, NFĸB is activated in both mutant and wild-type cells, abolishing the differential sensitivity. Moreover, JAK kinase activity is required for the differential sensitivity of JAK2V617F mutant cells, suggesting that the addition of JAK2 inhibitors to SMAC mimetics would detract from the ability of SMAC mimetics to selectively target JAK2V617F mutant cells. Instead, combination therapy with other agents that reduce inflammatory cytokines but preserve JAK2 signaling in mutant cells may be a more beneficial combination therapy in MPN.

In the original PDF online version of this article, the references 22–26 were missing.These are the missing references.

Electronic cigarettes (E-cigs) generate nicotine containing aerosols for inhalation and have emerged as a popular tobacco product among adolescents and young adults, yet little is known about their health effects due to their relatively recent introduction. Few studies have assessed the long-term effects of inhaling E-cigarette smoke or vapor. Here, we show that two months of E-cigarette exposure causes suppression of bone marrow hematopoietic stem and progenitor cells (HSPCs). Specifically, the common myeloid progenitors and granulocyte-macrophage progenitors were decreased in E-cig exposed animals compared to air exposed mice. Competitive reconstitution in bone marrow transplants was not affected by two months of E-cig exposure. When air and E-cig exposed mice were challenged with an inflammatory stimulus using lipopolysaccharide (LPS), competitive fitness between the two groups was not significantly different. However, mice transplanted with bone marrow from E-cigarette plus LPS exposed mice had elevated monocytes in their peripheral blood at five months post-transplant indicating a myeloid bias similar to responses of aged hematopoietic stem cells (HSC) to an acute inflammatory challenge. We also investigated whether E-cigarette exposure enhances the selective advantage of hematopoietic cells with myeloid malignancy associated mutations. E-cigarette exposure for one month slightly increased JAK2V617F mutant cells in peripheral blood but did not have an impact on TET2-/- cells. Altogether, our findings reveal that chronic E-cigarette exposure for two months alters the bone marrow HSPC populations but does not affect HSC reconstitution in primary transplants.

Measurements of elastic electron scattering data within the past decade have highlighted two-photon exchange contributions as a necessary ingredient in theoretical calculations to precisely evaluate hydrogen elastic scattering cross sections. This correction can modify the cross section at the few percent level. In contrast, dispersive effects can cause significantly larger changes from the Born approximation. The purpose of this experiment is to extract the carbon-12 elastic cross section around the first diffraction minimum, where the Born term contributions to the cross section are small to maximize the sensitivity to dispersive effects. The analysis uses the LEDEX data from the high resolution Jefferson Lab Hall A spectrometers to extract the cross sections near the first diffraction minimum of 12C at beam energies of 362 MeV and 685 MeV. The results are in very good agreement with previous world data, although with less precision. The average deviation from a static nuclear charge distribution expected from linear and quadratic fits indicate a 30.6% contribution of dispersive effects to the cross section at 1 GeV. The magnitude of the dispersive effects near the first diffraction minimum of 12C has been confirmed to be large with a strong energy dependence and could account for a large fraction of the magnitude for the observed quenching of the longitudinal nuclear response. These effects could also be important for nuclei radii extracted from parity-violating asymmetries measured near a diffraction minimum.

Thrombosis is a major cause of mortality in patients with myeloproliferative neoplasms (MPNs), though there is currently little to offer patients with MPN beyond aspirin and cytoreductive therapies such as hydroxyurea for primary prevention. Thrombogenesis in MPN involves multiple cellular mechanisms, including platelet activation and neutrophil-extracellular trap formation; therefore, an antithrombotic agent that targets one or more of these processes would be of therapeutic benefit in MPN. Here, we treated the JAK2V617F knockin mouse model of polycythemia vera with N-acetylcysteine (NAC), a sulfhydryl-containing compound with broad effects on glutathione replenishment, free radical scavenging, and reducing disulfide bonds, to investigate its antithrombotic effects in the context of MPN. Strikingly, NAC treatment extended the lifespan of JAK2V617F mice without impacting blood counts or splenomegaly. Using an acute pulmonary thrombosis model in vivo, we found that NAC reduced thrombus formation to a similar extent as the irreversible platelet inhibitor aspirin. In vitro analysis of platelet activation revealed that NAC reduced thrombin-induced platelet-leukocyte aggregate formation in JAK2V617F mice. Furthermore, NAC reduced neutrophil extracellular trap formation in primary human neutrophils from patients with MPN as well as healthy controls. These results provide evidence that N-acetylcysteine inhibits thrombosis in JAK2V617F mice and provide a pre-clinical rationale for investigating NAC as a therapeutic to reduce thrombotic risk in MPN.

Non-Hodgkin lymphoma (NHL) contributes to significant cancer burden and mortality globally. In recent years, much insight into the causes of NHL has been gained by evaluating global differences through international collaboration and data pooling. NHL comprises different subtypes that are known to behave differently, exhibit different prognoses, and start in distinct cell types (B-cell, T-cell, and NK-cell, predominantly), and there is increasing evidence that NHL subtypes have different etiologies. Classification of NHL can be complex, with varying subtype frequencies, and is a consideration when evaluating geographic differences. Because of this, international pooling of well-executed epidemiologic studies has conferred power to evaluate NHL by subtype and confidence with minimal misclassification. Given the decreasing burden in some regions while cases rise in Asia, and especially China, this report focuses on a review of the established etiology of NHL from the epidemiologic literature in recent decades, highlighting work from China. Topics covered include demographic patterns and genetic determinants including family history of NHL, as well as infection and immunosuppression, lifestyle, environment, and certain occupational exposures contributing to increased disease risk.

Although crops often respond immediately to enriched CO2 concentrations (e.g., increased photosynthesis), this initial response is often not sustained throughout production, thus reducing the benefit of this input. For horticulture species, the timing and extent of these acclimation responses are still widely uncertain. Therefore, the objective of this research was to determine species-specific acclimation responses to elevated CO2 concentrations for pansy (Viola ×wittrockiana ‘Matrix Blue Blotch Improved’) and petunia (Petunia ×hybrida ‘Dreams Midnight’). Seedlings were transplanted to 11.5-cm pots and placed in growth chambers with air temperature, relative humidity, and radiation intensity setpoints of 21 °C, 55%, and 250 μmol⋅m−2⋅s−1, respectively. Carbon dioxide treatments were established using the two growth chambers with setpoints of either 400 (ambient) or 1000 μmol⋅mol−1 (elevated) maintained during a 16-hour photoperiod. In addition to data collected through destructive harvest, the rate of photosynthesis (A) in response to increasing internal leaf CO2 concentration (A-Ci) and at the operating CO2 concentration (A-Ca) were measured weekly with a portable leaf photosynthesis system at saturating [A-Ci (1000 μmol⋅m−2⋅s−1)] or production [A-Ca (250 μmol⋅m−2⋅s−1)] radiation intensities. For both pansy and petunia, elevated CO2 produced greater total shoot dry mass than ambient CO2 after 4 weeks. However, the decreased maximum rate of photosynthetic electron transport, maximum rate of Rubisco carboxylase, and triose phosphate utilization rate of both species were also observed under elevated CO2. Similarly, A measured at 400 and 1000 μmol⋅mol−1 was reduced for both pansy and petunia grown under the elevated compared with ambient CO2 concentration based on A-Ca responses after 7 days, indicating quick physiological acclimation to this input. These results provide information regarding the timing and extent of physiological acclimation in response to elevated CO2 concentrations. However, because of physiological acclimation potentially occurring within 7 days of treatment initiation, additional research is necessary to develop species-specific recommendations for controlled environment production.

Historically, colorectal cancer (CRC) screening rates have been lower among African Americans. Previous studies that have examined the relationship between community characteristics and adherence to CRC screening have generally focused on a single community parameter, making it challenging to evaluate the overall impact of the social and built environment. In this study, we will estimate the overall effect of social and built environment and identify the most important community factors relevant to CRC screening. Data are from the Multiethnic Prevention and Surveillance Study (COMPASS), a longitudinal study among adults in Chicago, collected between May 2013 to March 2020. A total 2,836 African Americans completed the survey. Participants’ addresses were geocoded and linked to seven community characteristics (i.e., community safety, community crime, household poverty, community unemployment, housing cost burden, housing vacancies, low food access). A structured questionnaire measured adherence to CRC screening. Weighted quantile sum (WQS) regression was used to evaluate the impact of community disadvantages on CRC screening. When analyzing all community characteristics as a mixture, overall community disadvantage was associated with less adherence to CRC screening even after controlling for individual-level factors. In the adjusted WQS model, unemployment was the most important community characteristic (37.6%), followed by community insecurity (26.1%) and severe housing cost burden (16.3%). Results from this study indicate that successful efforts to improve adherence to CRC screening rates should prioritize individuals living in communities with high rates of insecurity and low socioeconomic status.

Purpose : To assess household air pollution levels in urban Chicago households and examine how socioeconomic factors influence these levels. Methods : We deployed wireless air monitoring devices to 244 households in a diverse population in Chicago to continuously record household fine particulate matter (PM _2.5 ) concentration. We calculated hourly average PM _2.5 concentration in a 24-hour cycle. Four factors—race, household income, area deprivation, and exposure to smoking—were considered in this study. Results : A total of 93085 h of exposure data were recorded. The average household PM _2.5 concentration was 43.8 μg m ^−3 . We observed a significant difference in the average household PM _2.5 concentrations between Black/African American and non-Black/African American households (46.3 versus 31.6 μg m ^−3 ), between high-income and low-income households (18.2 versus 52.5 μg m ^−3 ), and between smoking and non-smoking households (69.7 versus 29.0 μg m ^−3 ). However, no significant difference was observed between households in less and more deprived areas (43.7 versus 43.0 μg m ^−3 ). Implications : Household air pollution levels in Chicago households are much higher than the recommended level, challenging the hypothesis that household air quality is adequate for populations in high income nations. Our results indicate that it is the personal characteristics of participants, rather than the macro environments, that lead to observed differences in household air pollution.