Long-Term Aspirin Use and Self-Reported Walking Speed in Older Men: The Physicians' Health Study.

Background: Mobility limitation is a component of frailty that shares a bidirectional relationship with cardiovascular disease (CVD). Data are limited on the role of established CVD prevention therapies, such as aspirin, for prevention of frailty and mobility limitation.

Objectives: Examine the association between long-term aspirin use and walking speed.

Exploring Overweight Risk Trajectories During Childhood and Their Associations With Elevated Blood Pressure at Late Adolescence: a Retrospective Cohort Study.

Background: Overweight during childhood is significantly associated with higher risk of high blood pressure (HBP) in later life. However, recognition of critical intervention period is limited. We aimed to analyze the changes in overweight risk during school-age and its relationship with HBP.

Interface and Sensitive Characteristics of the Viscoelastic Film Used in a Surface Acoustic Wave Gas Sensor.

The surface morphology of viscoelastic-sensitive films significantly affects sensing characteristics of surface acoustic wave (SAW) sensors. Uniformity and compactness of the film surface directly influences detectability of the SAW sensor toward target gases. Viscoelastic fluoroalcoholpolysiloxane (SXFA) was prepared in this work using spin coating technology on an SAW delay line of 200 MHz and then used as coating for detection of dimethyl methylphosphonate (DMMP).

Combined Endoscopic and Radiologic Healing Is Associated With a Better Prognosis Than Endoscopic Healing Only in Patients With Crohn's Disease Receiving Anti-TNF Therapy.

Introduction: Although endoscopic healing (EH) is recommended as the therapeutic goal in patients with Crohn's disease (CD), combined EH and radiologic healing (RH) could be a more ideal therapeutic goal considering the transmural nature of CD. We compared the prognosis of patients with CD who achieved EH, RH, both EH and RH (deep healing; DH), or no healing under treatment with anti-tumor necrosis factor (TNF) agents.

Methods: We analyzed 392 patients with CD who received anti-TNF treatment for more than 1 year and evaluated with CT enterography or magnetic resonance enterography together with colonoscopy within 3 months between July 2017 and December 2018.

Circulating Metabolome and White Matter Hyperintensities in Women and Men.

Background: White matter hyperintensities (WMH), identified on T2-weighted magnetic resonance images of the human brain as areas of enhanced brightness, are a major risk factor of stroke, dementia, and death. There are no large-scale studies testing associations between WMH and circulating metabolites.

Methods: We studied up to 9290 individuals (50.

Advances in mixed cell deconvolution enable quantification of cell types in spatial transcriptomic data.

Mapping cell types across a tissue is a central concern of spatial biology, but cell type abundance is difficult to extract from spatial gene expression data. We introduce SpatialDecon, an algorithm for quantifying cell populations defined by single cell sequencing within the regions of spatial gene expression studies. SpatialDecon incorporates several advancements in gene expression deconvolution.

Strong, Ductile, and Tough Nanocrystal-Assembled Freestanding Gold Nanosheets.

The structural and mechanical properties of low-dimensional nanostructured metals have been attracting tremendous interest in the fast-growing fields of nanosciences and nanotechnologies. However, it still remains a challenge today to develop strong yet ductile low-dimensional metals that can support the further development of nanodevices. Here, through the polymer-assisted assembly of gold nanocrystals, we successfully fabricated the freestanding, ultrathin gold nanomaterial.

Gridization-Driven Mesoscale Self-Assembly of Conjugated Nanopolymers into Luminescence-Anisotropic Photonic Crystals.

Organic semiconducting emitters integrated with butterfly-mimetic photonic crystals (PhCs) are fascinating for dramatic advantages over light outcoupling efficiency and multifunctional strain sensors, as well as the key step toward electrically pumped lasers. Herein, an unprecedentedly direct mesoscale self-assembly into 1D PhCs is reported through a covalently gridization-driven approach of wide-bandgap conjugated polymers. A simple solvent-casting procedure allows for in situ self-assembly of the state-of-the-art conjugated nanopolymer, poly{[4-(octyloxy)-9,9-diphenylfluoren-2,7-diyl]grid}-co-{[5-(octyloxy)-9,9-diphenylfluoren-2,7-diyl]grid} (PODPFG), into well-defined multilayer architectures with an excellent toughness (30-40 J m ).

Influence of the Aspect Ratio of Iron Oxide Nanorods on Hysteresis-Loss-Mediated Magnetic Hyperthermia.

Owing to the problems associated with conventional cancer treatment methods, magnetic hyperthermia-based cancer therapy has gained importance recently. Achieving the desired heating effect at the site of the tumor with a minimal concentration of iron oxide nanoparticles (IONPs) and a safer field is necessary to explore the advantages of hyperthermia. For one to address this challenge, biocompatible IONPs with a desirable magnetic response at a tolerable field are necessary.

Quantifying Benefit-Risk Preferences for Heart Failure Devices: A Stated-Preference Study.

Background: Regulatory and clinical decisions involving health technologies require judgements about relative importance of their expected benefits and risks. We sought to quantify heart-failure patients' acceptance of therapeutic risks in exchange for improved effectiveness with implantable devices.

Methods: Individuals with heart failure recruited from a national web panel or academic medical center completed a web-based discrete-choice experiment survey in which they were randomized to one of 40 blocks of 8 experimentally controlled choice questions comprised of 2 device scenarios and a no-device scenario.

Anthrax toxins regulate pain signaling and can deliver molecular cargoes into ANTXR2 DRG sensory neurons.

Bacterial products can act on neurons to alter signaling and function. In the present study, we found that dorsal root ganglion (DRG) sensory neurons are enriched for ANTXR2, the high-affinity receptor for anthrax toxins. Anthrax toxins are composed of protective antigen (PA), which binds to ANTXR2, and the protein cargoes edema factor (EF) and lethal factor (LF).

HLA-A02:01 restricted T cell receptors against the highly conserved SARS-CoV-2 polymerase cross-react with human coronaviruses.

Cross-reactivity and direct killing of target cells remain underexplored for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific CD8 T cells. Isolation of T cell receptors (TCRs) and overexpression in allogeneic cells allows for extensive T cell reactivity profiling. We identify SARS-CoV-2 RNA-dependent RNA polymerase (RdRp/NSP12) as highly conserved, likely due to its critical role in the virus life cycle.

Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma.

Background: The prognosis of patients with early relapsed or refractory large B-cell lymphoma after the receipt of first-line chemoimmunotherapy is poor.

Methods: In this international, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with large B-cell lymphoma that was refractory to or had relapsed no more than 12 months after first-line chemoimmunotherapy to receive axicabtagene ciloleucel (axi-cel, an autologous anti-CD19 chimeric antigen receptor T-cell therapy) or standard care (two or three cycles of investigator-selected, protocol-defined chemoimmunotherapy, followed by high-dose chemotherapy with autologous stem-cell transplantation in patients with a response to the chemoimmunotherapy). The primary end point was event-free survival according to blinded central review.

The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group.

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis.

Synergy between dynamic covalent boronic ester and boron-nitrogen coordination: strategy for self-healing polyurethane elastomers at room temperature with unprecedented mechanical properties.

Achieving mechanical robustness and highly efficient self-healing simultaneously at room temperature is always a formidable challenge for polymeric materials. Herein, a series of novel supramolecular polyurethane elastomers (SPUEs) are developed by incorporating dynamic covalent boronic ester and boron-nitrogen (B-N) coordination. The SPUEs demonstrate the highest tensile toughness (∼182.

Genetic ablation of Pim1 or pharmacologic inhibition with TP-3654 ameliorates myelofibrosis in murine models.

Myelofibrosis (MF) is the deadliest form of myeloproliferative neoplasm (MPN). The JAK inhibitor Ruxolitinib can reduce constitutional symptoms but it does not substantially improve bone marrow fibrosis. Pim1 expression is significantly elevated in MPN/MF hematopoietic progenitors.

Effectiveness of a surveillance program of upper endoscopy for upper gastrointestinal cancers in Lynch syndrome patients.

Background And Aims: Lynch syndrome (LS) is the most common cause of hereditary colorectal cancer and is associated with an increased lifetime risk of gastric and duodenal cancers of 8-16% and 7%, respectively; therefore, we aim to describe an esophagogastroduodenoscopy (EGD) surveillance program for upper gastrointestinal (GI) precursor lesions and cancer in LS patients.

Methods: Patients who either had positive genetic testing or met clinical criteria for LS who had a surveillance EGD at our institution from 1996 to 2017 were identified. Patients were included if they had at least two EGDs or an upper GI cancer detected on the first surveillance EGD.

3D printable, tough, magnetic hydrogels with programmed magnetization for fast actuation.

Magnetic hydrogels have demonstrated great potential in soft robots, drug delivery, and bioengineering, and their functions are usually determined by the deforming capability. However, most magnetic hydrogels are embedded with soft magnetic particles ( FeO), where the magnetic domains cannot be programmed and retained under external magnetic fields. Here, we present a strategy to prepare a microgel-reinforced magnetic hydrogel, embedded with hard magnetic NdFeB particles.

Loss of Endothelial TSPAN12 Promotes Fibrostenotic Eosinophilic Esophagitis via Endothelial Cell-Fibroblast Crosstalk.

Background & Aims: Eosinophilic esophagitis (EoE) can progress to fibrostenosis by unclear mechanisms. Herein, we investigated gene dysregulation in fibrostenotic EoE, its association with clinical parameters and specific pathways, and the functional consequences.

Methods: Esophageal biopsies from subjects with EoE were collected across 11 Consortium of Eosinophilic Gastrointestinal Disease Researchers sites (n = 311) and 2 independent replication cohorts (n = 83).

Fasting drives the metabolic, molecular and geroprotective effects of a calorie-restricted diet in mice.

Calorie restriction (CR) promotes healthy ageing in diverse species. Recently, it has been shown that fasting for a portion of each day has metabolic benefits and promotes lifespan. These findings complicate the interpretation of rodent CR studies, in which animals typically eat only once per day and rapidly consume their food, which collaterally imposes fasting.

A Human Pleiotropic Multiorgan Condition Caused by Deficient Wnt Secretion.

Background: Structural birth defects occur in approximately 3% of live births; most such defects lack defined genetic or environmental causes. Despite advances in surgical approaches, pharmacologic prevention remains largely out of reach.

Methods: We queried worldwide databases of 20,248 families that included children with neurodevelopmental disorders and that were enriched for parental consanguinity.

Race, Genetic Ancestry, and Estimating Kidney Function in CKD.

Background: The inclusion of race in equations to estimate the glomerular filtration rate (GFR) has become controversial. Alternative equations that can be used to achieve similar accuracy without the use of race are needed.

Methods: In a large national study involving adults with chronic kidney disease, we conducted cross-sectional analyses of baseline data from 1248 participants for whom data, including the following, had been collected: race as reported by the participant, genetic ancestry markers, and the serum creatinine, serum cystatin C, and 24-hour urinary creatinine levels.