The Burden of Cardiovascular Disease in the Post-COVID Era.

In 2019, before the COVID-19 pandemic, cardiovascular disease (CVD) was the leading cause of death. Since 2020, the pandemic has had far-reaching effects on the landscape of health care including CVD prevention and management. Recent decreases in life expectancy in the United States could potentially be explained by issues related to disruptions in CVD prevention and control of CVD risk factors from the COVID-19 pandemic. This article reviews the effects of the SARS-CoV-2 virus and the accompanying pandemic on CVD risk factor prevention and management in the United States. Potential solutions are also proposed for these patients.

Diagnostic Accuracy of Office Blood Pressure Measurement and Home Blood Pressure Monitoring for Hypertension Screening Among Adults: Results From the IDH Study.

BACKGROUND: Using high awake blood pressure (BP; ≥130/80 mm Hg) on ambulatory BP monitoring (ABPM) as a reference, the purpose of this study was to determine the accuracy of high office BP (≥130/80 mm Hg) at an initial visit and high confirmatory office BP (≥130/80 mm Hg), and separately, high home BP (≥130/80 mm Hg) among participants with high office BP (≥130/80 mm Hg) at an initial office visit. METHODS AND RESULTS: The accuracy of office BP measurements using the oscillometric method for detecting high BP on ABPM was determined among 379 participants with complete office BP and ABPM data in the IDH (Improving the Detection of Hypertension) study. For detecting high BP on ABPM, the accuracy of high confirmatory office BP using the oscillometric method and, separately, high home BP was also determined among the subgroup of 122 participants with high office BP at an initial visit and complete home BP monitoring data. High office BP had moderate sensitivity (0.61 [95% CI, 0.53-0.68]) and high specificity (0.85 [95% CI, 0.80-0.90]) for high awake BP. High confirmatory office BP and high home BP had moderate sensitivity (0.69 [95% CI, 0.59-0.79] and 0.79 [95% CI, 0.71-0.87], respectively) and low and moderate specificity (0.44 [95% CI, 0.27-0.61] and 0.72 [95% CI, 0.56-0.88], respectively). CONCLUSIONS: Many individuals with high BP on ABPM do not have high office BP. Confirmatory office BP and home blood pressure monitoring also had limited ability to identify individuals with high BP on ABPM.

Use of Different Blood Pressure Thresholds to Reduce the Number of Home Blood Pressure Monitoring Days Needed for Detecting Hypertension.

BACKGROUND: Home blood pressure (BP) monitoring over a 7-day period is recommended to confirm the diagnosis of hypertension. METHODS: We determined upper and lower home BP thresholds with >90% positive predictive value and >90% negative predictive value using 1 to 6 days of monitoring to identify high home BP (systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg) based on 7 days of home BP monitoring. The sample included 361 adults from the Improving the Detection of Hypertension Study who were not taking antihypertensive medication. We used two 7-day periods, at least 3 days apart, the first being a sampling period and the second a reference period. For each number of days in the sampling period, we determined the percentage of participants who had a high likelihood of having (>90% positive predictive value) or not having (>90% negative predictive value) high BP and would not need to continue home BP monitoring. Only the participants in an uncertain category (ie, positive predictive value ≤90% and negative predictive value ≤90%) after each day were carried forward to the next day of home BP monitoring. RESULTS: Of the 361 participants (mean [SD] age of 41.3 [13.2] years; 60.4% women), 38.0% had high home BP during the reference period. There were 63.7%, 17.1%, 10.5%, 3.3%, 3.6%, and 1.4% participants who would not need to continue after 1, 2, 3, 4, 5, and 6 days of monitoring. CONCLUSIONS: In most people, high home BP can be identified or excluded with a high degree of confidence with 3 days or less of monitoring.

A population-scale temporal case-control evaluation of COVID-19 disease phenotype and related outcome rates in patients with cancer in England (UKCCP).

Patients with cancer are at increased risk of hospitalisation and mortality following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the SARS-CoV-2 phenotype evolution in patients with cancer since 2020 has not previously been described. We therefore evaluated SARS-CoV-2 on a UK populationscale from 01/11/2020-31/08/2022, assessing case-outcome rates of hospital assessment(s), intensive care admission and mortality. We observed that the SARS-CoV-2 disease phenotype has become less severe in patients with cancer and the non-cancer population. Case-hospitalisation rates for patients with cancer dropped from 30.58% in early 2021 to 7.45% in 2022 while case-mortality rates decreased from 20.53% to 3.25%. However, the risk of hospitalisation and mortality remains 2.10x and 2.54x higher in patients with cancer, respectively. Overall, the SARS-CoV-2 disease phenotype is less severe in 2022 compared to 2020 but patients with cancer remain at higher risk than the non-cancer population. Patients with cancer must therefore be empowered to live more normal lives, to see loved ones and families, while also being safeguarded with expanded measures to reduce the risk of transmission.

The National COVID Cancer Antibody Survey: a hyper-accelerated study proof of principle for cancer research.

The COVID-19 pandemic has led to a range of novel and adaptive research designs. In this perspective, we use our experience coordinating the National COVID Cancer Antibody Survey to demonstrate how a balance between speed and integrity can be achieved within a hyper-accelerated study design. Using the COVID-19 pandemic as an example, we show this approach is necessary in the face of uncertain and evolving situations wherein reliable information is needed in a timely fashion to guide policy. We identify streamlined participant involvement, healthcare systems integration, data architecture and real-world real-time analytics as key areas that differentiate this design from traditional cancer trials, and enable rapid results. Caution needs to be taken to avoid the exclusion of patient subgroups without digital access or literacy. We summarise the merits and defining features of hyper-accelerated cancer studies.

Immediate improvements in post-stroke gait biomechanics are induced with both real-time limb position and propulsive force biofeedback.

BACKGROUND: Paretic propulsion [measured as anteriorly-directed ground reaction forces (AGRF)] and trailing limb angle (TLA) show robust inter-relationships, and represent two key modifiable post-stroke gait variables that have biomechanical and clinical relevance. Our recent work demonstrated that real-time biofeedback is a feasible paradigm for modulating AGRF and TLA in able-bodied participants. However, the effects of TLA biofeedback on gait biomechanics of post-stroke individuals are poorly understood. Thus, our objective was to investigate the effects of unilateral, real-time, audiovisual TLA versus AGRF biofeedback on gait biomechanics in post-stroke individuals. METHODS: Nine post-stroke individuals (6 males, age 63 ± 9.8 years, 44.9 months post-stroke) participated in a single session of gait analysis comprised of three types of walking trials: no biofeedback, AGRF biofeedback, and TLA biofeedback. Biofeedback unilaterally targeted deficits on the paretic limb. Dependent variables included peak AGRF, TLA, and ankle plantarflexor moment. One-way repeated measures ANOVA with Bonferroni-corrected post-hoc comparisons were conducted to detect the effect of biofeedback on gait biomechanics variables. RESULTS: Compared to no-biofeedback, both AGRF and TLA biofeedback induced unilateral increases in paretic AGRF. TLA biofeedback induced significantly larger increases in paretic TLA than AGRF biofeedback. AGRF biofeedback increased ankle moment, and both feedback conditions increased non-paretic step length. Both types of biofeedback specifically targeted the paretic limb without inducing changes in the non-paretic limb. CONCLUSIONS: By showing comparable increases in paretic limb gait biomechanics in response to both TLA and AGRF biofeedback, our novel findings provide the rationale and feasibility of paretic TLA as a gait biofeedback target for post-stroke individuals. Additionally, our results provide preliminary insights into divergent biomechanical mechanisms underlying improvements in post-stroke gait induced by these two biofeedback targets. We lay the groundwork for future investigations incorporating greater dosages and longer-term therapeutic effects of TLA biofeedback as a stroke gait rehabilitation strategy. Trial registration NCT03466372.

Mst1 attenuates myocardial ischemia/reperfusion injury following heterotopic heart transplantation in mice through regulating Keap1/Nrf2 axis.

Ischemia reperfusion (I/R) injury remains a frequent adverse event that accompanies heart transplantation. Oxidative stress and aberrant production of free radicals were regarded as the culprit of cell death and tissue damage in post-transplant IR injury. Mst1 has been identified as a mediator of oxidative stress and Nrf2 regulates anti-oxidative enzymes, however, the interaction between Mst1 and Nrf2 anti-oxidative stress pathway remains to be clarified in the event of cardiac IR injury. Herein, the model of ischemia-reperfusion injury in heterotopic heart transplantation mice was firstly established.. We observed that cardiac IR induced upregulation of Mst1 and activation of Nrf2/HO-1pathway in mice receiving heterotopic heart transplantation. Further Cobalt dichloride-induced oxidative stress model of RAW264.7 macrophage cells were then established to mimic cardiac I/R injury, results showed that exposure to CoCl2 induced the upregulation of Mst1 and activation of Keap1/Nrf2 pathway, and genetic ablation of Mst-1 and inhibition of Keap1/Nrf2 pathway aggravated oxidative damage in those cells. Additional in vivo study showed that transfection of Mst1 shRNA spurred ROS generation and worsened cardiac damage in IR mice. Meanwhile, Mst1-KD mice receiving heart transplantation showed markedly downregulation of Nrf2, HO-1 yet upregulation of Keap1, indicating diminished protective effect against tissue damage caused by IR probably owing to the frustration of Keap1/Nrf2 pathway. Taken together, our findings demonstrated the protective effect of Mst1 from cardiac IR injury via triggering Keap1/Nrf2 axis and suppressing ROS generation, which shed light on the promising role of Mst1 in transitional management of IR injury resulted from cardiac transplantation.

Association of SARS-CoV-2 Spike Protein Antibody Vaccine Response With Infection Severity in Patients With Cancer: A National COVID Cancer Cross-sectional Evaluation.

Importance: Accurate identification of patient groups with the lowest level of protection following COVID-19 vaccination is important to better target resources and interventions for the most vulnerable populations. It is not known whether SARS-CoV-2 antibody testing has clinical utility for high-risk groups, such as people with cancer. Objective: To evaluate whether spike protein antibody vaccine response (COV-S) following COVID-19 vaccination is associated with the risk of SARS-CoV-2 breakthrough infection or hospitalization among patients with cancer. Design, Setting, and Participants: This was a population-based cross-sectional study of patients with cancer from the UK as part of the National COVID Cancer Antibody Survey. Adults with a known or reported cancer diagnosis who had completed their primary SARS-CoV-2 vaccination schedule were included. This analysis ran from September 1, 2021, to March 4, 2022, a period covering the expansion of the UK's third-dose vaccination booster program. Interventions: Anti-SARS-CoV-2 COV-S antibody test (Elecsys; Roche). Main Outcomes and Measures: Odds of SARS-CoV-2 breakthrough infection and COVID-19 hospitalization. Results: The evaluation comprised 4249 antibody test results from 3555 patients with cancer and 294 230 test results from 225 272 individuals in the noncancer population. The overall cohort of 228 827 individuals (patients with cancer and the noncancer population) comprised 298 479 antibody tests. The median age of the cohort was in the age band of 40 and 49 years and included 182 741 test results (61.22%) from women and 115 737 (38.78%) from men. There were 279 721 tests (93.72%) taken by individuals identifying as White or White British. Patients with cancer were more likely to have undetectable anti-S antibody responses than the general population (199 of 4249 test results [4.68%] vs 376 of 294 230 [0.13%]; P < .001). Patients with leukemia or lymphoma had the lowest antibody titers. In the cancer cohort, following multivariable correction, patients who had an undetectable antibody response were at much greater risk for SARS-CoV-2 breakthrough infection (odds ratio [OR], 3.05; 95% CI, 1.96-4.72; P < .001) and SARS-CoV-2-related hospitalization (OR, 6.48; 95% CI, 3.31-12.67; P < .001) than individuals who had a positive antibody response. Conclusions and Relevance: The findings of this cross-sectional study suggest that COV-S antibody testing allows the identification of patients with cancer who have the lowest level of antibody-derived protection from COVID-19. This study supports larger evaluations of SARS-CoV-2 antibody testing. Prevention of SARS-CoV-2 transmission to patients with cancer should be prioritized to minimize impact on cancer treatments and maximize quality of life for individuals with cancer during the ongoing pandemic.

Handheld ultrasound-guided cannulation of difficult hemodialysis arteriovenous access: A randomized controlled trial.

INTRODUCTION: Cannulation of complex arteriovenous fistula (AVF) or graft (AVG) frequently poses challenges to renal nursing practice. Ultrasound (US) guidance on visualizing central and peripheral venous access has been widely adopted in nephrology, reducing vascular intervention complications. Renal nurses could acquire this point-of-care technique to increase the successful cannulation rate while facilitating confidence build-up during practice. We aim to evaluate the use of handheld US on difficult AVF/AVG cannulation in a hospital-based dialysis unit. METHODS: We conducted a single-center randomized controlled trial from January 2021 to January 2022. Ten renal nurses were trained by an interventional nephrologist before patient recruitment and had completed a pre- and posttraining questionnaire on their confidence level. Fifty hemodialysis patients with complex AVF were randomized to US-guided or conventional cannulation. The total time spent on cannulation and patients' pain scores were also collected. FINDINGS: Renal nurses increased their confidence level after training (pretraining score 26.6 ± 6.9 vs. posttraining score 36.4 ± 3.0; p = 0.014). There was a higher success rate (only one cannulation attempt required) for US-guided (96%) versus conventional (72.0%) cannulation (p = 0.049). US-guided cannulation had a lower pain score than the conventional method (1.48 ± 0.73 vs. 2.13 ± 0.95, p = 0.012). The pre-cannulation assessment time and time spent on cannulation were comparable between the two groups. DISCUSSION: Our study showed that US-guided cannulation increased renal nurses' confidence level in difficult cannulation and improved success rate. Larger scale studies are required to further assess the applications of handheld US in AVF cannulation, particularly in different clinical settings (e.g., chronic dialysis centers).

Automated lung ultrasound image assessment using artificial intelligence to identify fluid overload in dialysis patients.

BACKGROUND: Fluid assessment is challenging, and fluid overload poses a significant problem among dialysis patients, with pulmonary oedema being the most serious consequence. Our study aims to develop a simple objective fluid assessment strategy using lung ultrasound (LUS) and artificial intelligence (AI) to assess the fluid status of dialysis patients. METHODS: This was a single-centre study of 76 hemodialysis and peritoneal dialysis patients carried out between July 2020 to May 2022. The fluid status of dialysis patients was assessed via a simplified 8-point LUS method using a portable handheld ultrasound device (HHUSD), clinical examination and bioimpedance analysis (BIA). The primary outcome was the performance of 8-point LUS using a portable HHUSD in diagnosing fluid overload compared to physical examination and BIA. The secondary outcome was to develop and validate a novel AI software program to quantify B-line count and assess the fluid status of dialysis patients. RESULTS: Our study showed a moderate correlation between LUS B-line count and fluid overload assessed by clinical examination (r = 0.475, p < 0.001) and BIA (r = 0.356. p < 0.001). The use of AI to detect B-lines on LUS in our study for dialysis patients was shown to have good agreement with LUS B lines observed by physicians; (r = 0.825, p < 0.001) for the training dataset and (r = 0.844, p < 0.001) for the validation dataset. CONCLUSION: Our study confirms that 8-point LUS using HHUSD, with AI-based detection of B lines, can provide clinically useful information on the assessment of hydration status and diagnosis of fluid overload for dialysis patients in a user-friendly and time-efficient way.

COVID-19: Third dose booster vaccine effectiveness against breakthrough coronavirus infection, hospitalisations and death in patients with cancer: A population-based study.

PURPOSE: People living with cancer and haematological malignancies are at an increased risk of hospitalisation and death following infection with acute respiratory syndrome coronavirus 2. Coronavirus third dose vaccine boosters are proposed to boost waning immune responses in immunocompromised individuals and increase coronavirus protection; however, their effectiveness has not yet been systematically evaluated. METHODS: This study is a population-scale real-world evaluation of the United Kingdom's third dose vaccine booster programme for cancer patients from 8th December 2020 to 7th December 2021. The cancer cohort comprises individuals from Public Health England's national cancer dataset, excluding individuals less than 18 years. A test-negative case-control design was used to assess the third dose booster vaccine effectiveness. Multivariable logistic regression models were fitted to compare risk in the cancer cohort relative to the general population. RESULTS: The cancer cohort comprised of 2,258,553 tests from 361,098 individuals. Third dose boosters were evaluated by reference to 87,039,743 polymerase chain reaction coronavirus tests. Vaccine effectiveness against breakthrough infections, symptomatic infections, coronavirus hospitalisation and death in cancer patients were 59.1%, 62.8%, 80.5% and 94.5%, respectively. Lower vaccine effectiveness was associated with a cancer diagnosis within 12 months, lymphoma, recent systemic anti-cancer therapy (SACT) or radiotherapy. Patients with lymphoma had low levels of protection from symptomatic disease. In spite of third dose boosters, following multivariable adjustment, individuals with cancer remain at an increased risk of coronavirus hospitalisation and death compared to the population control (OR 3.38, 3.01, respectively. p < 0.001 for both). CONCLUSIONS: Third dose boosters are effective for most individuals with cancer, increasing protection from coronavirus. However, their effectiveness is heterogenous and lower than the general population. Many patients with cancer will remain at the increased risk of coronavirus infections even after 3 doses. In the case of patients with lymphoma, there is a particularly strong disparity of vaccine effectiveness against breakthrough infection and severe disease. Breakthrough infections will disrupt cancer care and treatment with potentially adverse consequences on survival outcomes. The data support the role of vaccine boosters in preventing severe disease, and further pharmacological intervention to prevent transmission and aid viral clearance to limit the disruption of cancer care as the delivery of care continues to evolve during the coronavirus pandemic.

Discovery of a Redox-Activatable Chemical Probe for Detection of Cyclooxygenase-2 in Cells and Animals.

Cyclooxygenase-2 (COX-2) expression is up-regulated in inflammatory tissues and many premalignant and malignant tumors. Assessment of COX-2 protein in vivo, therefore, promises to be a powerful strategy to distinguish pathologic cells from normal cells in a complex disease setting. Herein, we report the first redox-activatable COX-2 probe, fluorocoxib Q (FQ), for in vivo molecular imaging of pathogenesis. FQ inhibits COX-2 selectively in purified enzyme and cell-based assays. FQ exhibits extremely low fluorescence and displays time- and concentration-dependent fluorescence enhancement upon exposure to a redox environment. FQ enters the cells freely and binds to the COX-2 enzyme. FQ exhibits high circulation half-life and metabolic stability sufficient for target site accumulation and demonstrates COX-2-targeted uptake and retention in cancer cells and pathologic tissues. Once taken up, it undergoes redox-mediated transformation into a fluorescent compound fluorocoxib Q-H that results in high signal-to-noise contrast and differentiates pathologic tissues from non-pathologic tissues for real-time in vivo imaging.

Facile synthesis of chitosan-based nanogels through photo-crosslinking for doxorubicin delivery.

Chitosan-based nanogels are effective carriers for drug delivery due to their biocompatibility and biodegradability. However, the chemically cross-linked nanogels usually require complicated procedures or tough conditions. Herein, we report a simple approach to generate chitosan-based nanogels by photo-crosslinking of poor solvent-induced nanoaggregates without requiring any emulsifying agent, catalyst, or external crosslinker. O-nitrobenzyl alcohol-modified carboxymethyl chitosan was synthesized and self-crosslinked into the nanogels in a mixed solution of ethanol and water under 365 nm light irradiation due to UV-induced primary amine and o-nitrobenzyl alcohol cyclization. The nanogels (CMC-NBA NPs) and lactobionic acid-decorated nanogels (LACMC-NBA NPs) displayed a uniform diameter (~200 nm) and excellent stability under physiological conditions. Notably, the nanogels exhibited a high loading content (~28 %) due to π-π stacking and electrostatic interactions between doxorubicin (DOX) and the carriers. These DOX-loaded nanogels showed rapid drug release under slightly acidic conditions. The cell and animal experiments confirmed that LACMC-NBA NPs increased cellular uptake, improved cytotoxicity in tumor cells, and enhanced growth inhibition in vivo than CMC-NBA NPs. Thus, these photo-crosslinked nanogels possess great potential for DOX delivery.

Diselenide-crosslinked carboxymethyl chitosan nanoparticles for doxorubicin delivery: Preparation and in vivo evaluation.

In this paper, we report a simple approach to fabricate diselenide-crosslinked carboxymethyl chitosan nanoparticles (DSe-CMC NPs) for doxorubicin (DOX) delivery, with disulfide analogs (DS-CMC NPs) as control. DS-CMC NPs and DSe-CMC NPs featured a spherical morphology and narrow size distribution with the average size about 200 nm. Carboxymethyl chitosan (CMC) as the starting material not only improved the biocompatibility of the nanocarriers but also enhanced physiological stability. Due to electrostatic interactions between DOX and CMC, the nanoparticles had high drug encapsulation efficiency (∼25 %). The nanoparticles disintegration and drug release were accelerated by the cleavage of diselenide bonds through oxidation by H2O2 or reduction by GSH. In vitro cell experiments revealed that DOX-loaded DSe-CMC NPs possessed the highest drug accumulation and cytotoxicity in tumor cells. Moreover, DOX-loaded DSe-CMC NPs performed the enhanced growth inhibition in vivo than that of DS-CMC NPs. Thus, the diselenide-crosslinked nanoparticles possess great potentials for DOX delivery.

Expression optimization, purification, and biophysical characterization of a GluN2D-containing NMDA receptor.

N-methyl-d-aspartate (NMDA) receptors are hetero-tetrameric ion channels typically consisting of two GluN1 and two GluN2 subunits. A GluN2D subunit containing NMDA receptor dysfunction has been implicated in several neurological diseases, including schizophrenia; however, the lack of a purified GluN2D containing NMDA receptor has been a hurdle for structural and biophysical studies. Here, we present expression and purification strategies to generate human GluN2D containing NMDA receptor, confirm its hetero-tetrameric form using fluorescence size exclusion chromatography (FSEC) and evaluated its suitability for structural studies. The purification methodology outlined here will help in the development of GluN2D specific channel modulators and enable structure activity relationship (SAR) studies.

Vaccine effectiveness against COVID-19 breakthrough infections in patients with cancer (UKCCEP): a population-based test-negative case-control study.

BACKGROUND: People with cancer are at increased risk of hospitalisation and death following infection with SARS-CoV-2. Therefore, we aimed to conduct one of the first evaluations of vaccine effectiveness against breakthrough SARS-CoV-2 infections in patients with cancer at a population level. METHODS: In this population-based test-negative case-control study of the UK Coronavirus Cancer Evaluation Project (UKCCEP), we extracted data from the UKCCEP registry on all SARS-CoV-2 PCR test results (from the Second Generation Surveillance System), vaccination records (from the National Immunisation Management Service), patient demographics, and cancer records from England, UK, from Dec 8, 2020, to Oct 15, 2021. Adults (aged ≥18 years) with cancer in the UKCCEP registry were identified via Public Health England's Rapid Cancer Registration Dataset between Jan 1, 2018, and April 30, 2021, and comprised the cancer cohort. We constructed a control population cohort from adults with PCR tests in the UKCCEP registry who were not contained within the Rapid Cancer Registration Dataset. The coprimary endpoints were overall vaccine effectiveness against breakthrough infections after the second dose (positive PCR COVID-19 test) and vaccine effectiveness against breakthrough infections at 3-6 months after the second dose in the cancer cohort and control population. FINDINGS: The cancer cohort comprised 377 194 individuals, of whom 42 882 had breakthrough SARS-CoV-2 infections. The control population consisted of 28 010 955 individuals, of whom 5 748 708 had SARS-CoV-2 breakthrough infections. Overall vaccine effectiveness was 69·8% (95% CI 69·8-69·9) in the control population and 65·5% (65·1-65·9) in the cancer cohort. Vaccine effectiveness at 3-6 months was lower in the cancer cohort (47·0%, 46·3-47·6) than in the control population (61·4%, 61·4-61·5). INTERPRETATION: COVID-19 vaccination is effective for individuals with cancer, conferring varying levels of protection against breakthrough infections. However, vaccine effectiveness is lower in patients with cancer than in the general population. COVID-19 vaccination for patients with cancer should be used in conjunction with non-pharmacological strategies and community-based antiviral treatment programmes to reduce the risk that COVID-19 poses to patients with cancer. FUNDING: University of Oxford, University of Southampton, University of Birmingham, Department of Health and Social Care, and Blood Cancer UK.

Integrated analysis of 14 lymphoma datasets revealed high expression of CXCL14 promotes cell migration in mantle cell lymphoma.

Lymphoma is accompanied by the impairment of multiple immune functions. Cytokines play an important role in a variety of immune-related functions and affect the tumor microenvironment. However, the exact regulatory mechanisms between them remain unclear. This study aimed to explore the cytokines expression and function in Hodgkin's lymphoma (HL), diffuse large B-cell lymphoma (DLBCL), and mantle cell lymphoma (MCL). We performed a transcriptome integration analysis of 14 lymphoma datasets including 240 Hodgkin's lymphoma, 891 diffuse large B-cell lymphoma, 216 mantle cell lymphoma, and 64 health samples. The results showed that multiple immune functions and signal pathway damage were shared by all three types of lymphoma, and these functions were related to cytokines. Furthermore, through co-expression network and functional interaction network analysis, we identified CXCL14 as a key regulator and it affects cell chemotaxis and migration functions. The functional experiment showed that CXCL14 knockdown inhibited cell migration in MCL cell lines. This study suggested that high expression of CXCL14 may aggravate MCL via promoting cell migration. Our findings provide novel insights into the biology of this disease and would be helpful for the pathogenesis study and drug discovery of lymphomas.

Automated, high-dimensional evaluation of physiological aging and resilience in outbred mice.

Behavior and physiology are essential readouts in many studies but have not benefited from the high-dimensional data revolution that has transformed molecular and cellular phenotyping. To address this, we developed an approach that combines commercially available automated phenotyping hardware with a systems biology analysis pipeline to generate a high-dimensional readout of mouse behavior/physiology, as well as intuitive and health-relevant summary statistics (resilience and biological age). We used this platform to longitudinally evaluate aging in hundreds of outbred mice across an age range from 3 months to 3.4 years. In contrast to the assumption that aging can only be measured at the limits of animal ability via challenge-based tasks, we observed widespread physiological and behavioral aging starting in early life. Using network connectivity analysis, we found that organism-level resilience exhibited an accelerating decline with age that was distinct from the trajectory of individual phenotypes. We developed a method, Combined Aging and Survival Prediction of Aging Rate (CASPAR), for jointly predicting chronological age and survival time and showed that the resulting model is able to predict both variables simultaneously, a behavior that is not captured by separate age and mortality prediction models. This study provides a uniquely high-resolution view of physiological aging in mice and demonstrates that systems-level analysis of physiology provides insights not captured by individual phenotypes. The approach described here allows aging, and other processes that affect behavior and physiology, to be studied with improved throughput, resolution, and phenotypic scope.