Explore the vast range of titles available.

Plain language summaries (PLSs) are intended to provide readers with a clear, nontechnical, and easily understandable overview of medical and scientific literature; however, audience preferences for specific PLS formats have yet to be fully explored. This study aims to evaluate the preferred readability level and format for PLSs of medical research articles of different disease states via a web-based survey of audiences of different age groups. Articles describing phase III clinical trials published in top-level, peer-reviewed journals between May 2016 and May 2018 were identified for 3 chronic disease states representing a range of adult patient age groups: (1) psoriasis, a skin disease representative of younger patients; (2) multiple sclerosis (MS), a neurological disease representative of middle-aged patients; and (3) rheumatoid arthritis (RA), a painful joint disease representative of older patients. Four PLSs were developed for each research article, of which 3 were text-only summaries (written with high, medium, and low complexity) and 1 was an infographic. To evaluate each of the 4 PLS formats, a 20-question open survey (specific to one of the 3 diseases) was sent to a representative sample selected via UK-based patient association websites, Twitter, and Facebook patient groups. A weighted-average calculation was applied to respondents' ranked preferences for each PLS format. For all 3 articles, the weighted-average preference scores showed that infographic (psoriasis 2.91, MS 2.71, and RA 2.78) and medium-complexity text-based PLS (reading age 14-17 years, US Grade 9-11; psoriasis 2.90; MS 2.47; RA 2.77) were the two most preferred PLS formats. Audience preferences should be accounted for when preparing PLSs to accompany peer-reviewed original research articles. Oversimplified text can be viewed negatively, and graphical summaries or medium-complexity text-based summaries appear to be the most popular. Patients and caregivers should have the chance to read about medical research in a format they can understand. However, we do not know much about the formats that people with different illnesses or ages prefer. Researchers wanted to find out more about this. They selected 3 medical articles about illnesses that affect different age groups: psoriasis (younger patients), multiple sclerosis (middle-aged patients), and rheumatoid arthritis (older patients). They created 4 summaries of each article. One was a graphical summary, and the other 3 were words-only summaries of high, medium, and low complexity. Then, the researchers posted surveys on UK patient group websites and Facebook patient groups to ask people what they thought of the summaries. The surveys were taken by 167 people. These people were patients with psoriasis, multiple sclerosis, or rheumatoid arthritis, or their caregivers. Most were women, and about half had a university degree. For each illness, most people preferred the graphical summary. Among the word-only summaries, most people preferred the medium-complexity wording written for a reading age of 14 to 17 years. People felt that the graphical and medium-complexity summaries were clear and concise, while the others used jargon or were too simple. Authors of medical articles should remember these results when writing summaries for patients. More research is needed about the preferences of other people, such as those with other illnesses. (See Multimedia Appendix 1 for the graphical summary of the plain language summary.).

The instruments best suited to performing high-energy-resolution neutron spectroscopy are spin-echo spectrometers and backscattering spectrometers. The development of these experimental techniques dates back almost half a century, and most major neutron scattering facilities operate mature spectrometers of one or both classes. Recent advances in instrumentation and neutron sources are enhancing their performance and expanding their capabilities, with the objective of enabling researchers to tackle new and more complex problems. In this Technical Review, we assess the current state of the art in high-energy-resolution neutron spectrometers, showcasing their role in the study of nanoscale dynamics in soft and biological materials, as well as disordered magnets.Neutron spectroscopy is a powerful probe to study the dynamics in materials. This Technical Review assesses the state-of-the-art experimental spectroscopic methods, which are optimized to provide high energy resolution and can reveal dynamic processes on the picosecond and nanosecond timescales.

Pulmonary alveolar microlithiasis is an autosomal recessive lung disease caused by a deficiency in the pulmonary epithelial Npt2b sodium-phosphate co-transporter that results in accumulation of phosphate and formation of hydroxyapatite microliths in the alveolar space. The single cell transcriptomic analysis of a pulmonary alveolar microlithiasis lung explant showing a robust osteoclast gene signature in alveolar monocytes and the finding that calcium phosphate microliths contain a rich protein and lipid matrix that includes bone resorbing osteoclast enzymes and other proteins suggested a role for osteoclast-like cells in the host response to microliths. While investigating the mechanisms of microlith clearance, we found that Npt2b modulates pulmonary phosphate homeostasis through effects on alternative phosphate transporter activity and alveolar osteoprotegerin, and that microliths induce osteoclast formation and activation in a receptor activator of nuclear factor-κB ligand and dietary phosphate dependent manner. This work reveals that Npt2b and pulmonary osteoclast-like cells play key roles in pulmonary homeostasis and suggest potential new therapeutic targets for the treatment of lung disease. Osteoclasts are derived from circulating myeloid cells to mediate bone repair, maintenance and remodeling. Here, the authors show that the lung also recruits and reprograms monocytes and alveolar macrophages into osteoclast-like cells to clear pathogenic particles from the airspace.

Few disciplines in contemporary clinical research have experienced the high expectations directed at the gene therapy field. However, gene therapy has been challenging to translate to the clinic, often because the therapeutic gene is expressed at insufficient levels in the patient or because the gene delivery vector integrates near protooncogenes, which can cause leukemia (see the Perspective by Verma ). Biffi et al. ( 1233158 , published online 11 July) and Aiuti et al. ( 1233151 ; published online 11 July) report progress on both fronts in gene therapy trials of three patients with metachromatic leukodystrophy (MLD), a neurodegenerative disorder, and three patients with Wiskott-Aldrich syndrome (WAS), an immunodeficiency disorder. Optimized lentiviral vectors were used to introduce functional MLD or WAS genes into the patients' hematopoietic stem cells (HSCs) ex vivo, and the transduced cells were then infused back into the patients, who were then monitored for up to 2 years. In both trials, the patients showed stable engraftment of the transduced HSC and high expression levels of functional MLD or WAS genes. Encouragingly, there was no evidence of lentiviral vector integration near proto-oncogenes, and the gene therapy treatment halted disease progression in most patients. A longer follow-up period will be needed to further validate efficacy and safety. Lentivirus-mediated gene therapy produces encouraging results in three children with a rare lysosomal storage disease. [Also see Perspective by Verma ] Metachromatic leukodystrophy (MLD) is an inherited lysosomal storage disease caused by arylsulfatase A (ARSA) deficiency. Patients with MLD exhibit progressive motor and cognitive impairment and die within a few years of symptom onset. We used a lentiviral vector to transfer a functional ARSA gene into hematopoietic stem cells (HSCs) from three presymptomatic patients who showed genetic, biochemical, and neurophysiological evidence of late infantile MLD. After reinfusion of the gene-corrected HSCs, the patients showed extensive and stable ARSA gene replacement, which led to high enzyme expression throughout hematopoietic lineages and in cerebrospinal fluid. Analyses of vector integrations revealed no evidence of aberrant clonal behavior. The disease did not manifest or progress in the three patients 7 to 21 months beyond the predicted age of symptom onset. These findings indicate that extensive genetic engineering of human hematopoiesis can be achieved with lentiviral vectors and that this approach may offer therapeutic benefit for MLD patients.

Nicotine vaping has surged in recent years, particularly among young adults, and is strongly linked with concurrent alcohol use. Separately, chronic excessive alcohol use drives hypertension and cardiomyopathy, while nicotine vaping is linked to a modest rise in cardiovascular disease incidence and mortality. However, little is known about how concurrent use interacts to affect protein expression in the cardiovascular system. The aim of this study was to determine differential cardiac protein expression in mice exposed to concurrent chronic-plus-binge alcohol and nicotine vaping use. Male C57BL6/J mice received a 20-day 5% ethanol diet with 5 g/kg ethanol binges on days 10 and 20, alongside isocaloric controls. During this period, they were also exposed nightly to either 5% nicotine salt vapor, vegetable glycerin/propylene glycol vehicle vapor, or room air. The left ventricular free wall was collected and analyzed using discovery-based proteomics and subsequent Ingenuity Pathway Analysis. A total of 3144 proteins were identified across all groups. Compared to air-exposed, control-fed mice, 201 proteins were significantly altered by ethanol, 101 proteins by nicotine vaping, and 159 proteins by combined exposure. Both ethanol and nicotine vaping influenced pathways involved in lipid homeostasis, extracellular matrix remodeling, and mitochondrial bioenergetics; however, these alterations did not uniformly manifest in the dual-use group. This pattern highlights the nonadditive and potentially interaction-dependent nature of alcohol and nicotine vaping effects on cardiovascular protein expression patterns that may contribute to a distinct functional phenotype.

Endogenously produced hydrogen sulfide (H2S) is critical for cardiovascular homeostasis. Therapeutic strategies aimed at increasing H2S levels have proven cardioprotective in models of acute myocardial infarction (MI) and heart failure (HF). The present study was undertaken to investigate the effects of a novel H2S prodrug, SG-1002, on stress induced hypertrophic signaling in murine HL-1 cardiac muscle cells. Treatment of HL-1 cells with SG-1002 under serum starvation without or with H2O2 increased the levels of H2S, H2S producing enzyme, and cystathionine β-synthase (CBS), as well as antioxidant protein levels, such as super oxide dismutase1 (SOD1) and catalase, and additionally decreased oxidative stress. SG-1002 also decreased the expression of hypertrophic/HF protein markers such as atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), galectin-3, TIMP1, collagen type III, and TGF-β1 in stressed HL-1 cells. Treatment with SG-1002 caused a significant induction of cell viability and a marked reduction of cellular cytotoxicity in HL-1 cells under serum starvation incubated without or with H2O2. Experimental results of this study suggest that SG-1002 attenuates myocardial cellular oxidative damage and/or hypertrophic signaling via increasing H2S levels or H2S producing enzymes, CBS, and antioxidant proteins.

The global targeted disruption of the natriuretic peptide receptor-A (NPRA) gene (Npr1) in mice provokes hypertension and cardiovascular dysfunction. The objective of this study was to determine the mechanisms regulating the development of cardiac fibrosis and dysfunction in Npr1 mutant mice. Npr1 knockout (Npr1−/−, 0-copy), heterozygous (Npr1+/−, 1-copy), and wild-type (Npr1+/+, 2-copy) mice were treated with the transforming growth factor (TGF)-β1 receptor (TGF-β1R) antagonist GW788388 (2 µg/g body weight/day; ip) for 28 days. Hearts were isolated and used for real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemical analyses. The Npr1−/− (0-copy) mice showed a 6-fold induction of cardiac fibrosis and dysfunction with markedly induced expressions of collagen-1α (3.8-fold), monocyte chemoattractant protein (3.7-fold), connective tissue growth factor (CTGF, 5.3-fold), α-smooth muscle actin (α-SMA, 6.1-fold), TGF-βRI (4.3-fold), TGF-βRII (4.7-fold), and phosphorylated small mothers against decapentaplegic (pSMAD) proteins, including pSMAD-2 (3.2-fold) and pSMAD-3 (3.7-fold), compared with wild-type mice. The expressions of phosphorylated extracellular-regulated kinase ERK1/2 (pERK1/2), matrix metalloproteinases-2, -9, (MMP-2, -9), and proliferating cell nuclear antigen (PCNA) were also significantly upregulated in Npr1 0-copy mice. The treatment of mutant mice with GW788388 significantly blocked the expression of fibrotic markers, SMAD proteins, MMPs, and PCNA compared with the vehicle-treated control mice. The treatment with GW788388 significantly prevented cardiac dysfunctions in a sex-dependent manner in Npr1 0-copy and 1-copy mutant mice. The results suggest that the development of cardiac fibrosis and dysfunction in mutant mice is predominantly regulated through the TGF-β1-mediated SMAD-dependent pathway.

M-CSF receptor signaling supports the development and survival of mononuclear phagocytes and is thought to play a role in post burn anemia by promoting myeloid lineage bias. We found M-CSF secretion was increased in burn patients and a murine model of post burn ACI, so we neutralized M-CSF in ACI mice to determine if erythropoiesis was improved. Instead, M-CSF blockade further impaired erythropoiesis and erythroid cells access to iron. M-CSF blockade enhanced inflammatory cytokine secretion, further increased systemic neutrophil counts, and led to tissue iron sequestration that was dependent, in part, on augmented IL-6 secretion which induced hepcidin. Deleterious effects of post burn M-CSF blockade were associated with arrest of an iron recycling gene expression signature in the liver and spleen that included Spi-C transcription factor and heme oxygenase-1, which promote heme metabolism and confer a non-inflammatory tone in macrophages. Hepatic induction of these factors in ACI mice was consistent with a recovery of ferroportin gene expression and reflected an M-CSF dependent expansion and differentiation of Spi-C+ monocytes into Kupffer cells. Together, this data indicates M-CSF secretion supports a homeostatic iron recycling program that plays a key role in the maintenance of erythroid cells access to iron following burn injury.

Development of pneumonia is the most lethal consequence of influenza, increasing mortality more than 50-fold compared with uncomplicated infection. The spread of viral infection from conducting airways to the alveolar epithelium is therefore a pivotal event in influenza pathogenesis. We found that mitogenic stimulation with keratinocyte growth factor (KGF) markedly accelerated mortality after infectious challenge with influenza A virus (IAV). Coadministration of KGF with IAV markedly accelerated the spread of viral infection from the airways to alveoli compared with challenge with IAV alone, based on spatial and temporal analyses of viral nucleoprotein staining of lung tissue sections and dissociated lung cells. To better define the temporal relationship between KGF administration and susceptibility to IAV infection in vivo, we administered KGF 120, 48, 24, and 0 h before intrapulmonary IAV challenge and assessed the percentages of proliferating and IAV-infected, alveolar type II (AECII) cells in dispersed lung cell populations. Peak AECII infectivity coincided with the timing of KGF administration that also induced peak AECII proliferation. AECII from mice that were given intrapulmonary KGF before isolation and then infected with IAV ex vivo exhibited the same temporal pattern of proliferation and infectious susceptibility. KGF-induced increases in mortality, AECII proliferation, and enhanced IAV susceptibility were all reversed by pretreatment of the animals with the mTOR inhibitor rapamycin before mitogenic stimulation. Taken together, these data suggest mTOR signaling-dependent, mitogenic conditioning of AECII is a determinant of host susceptibility to infection with IAV.