Miracle-dz/UniFAR-FTUs huggingface dataset:
Body mass index and weight change are associated with adult lung function trajectories: the prospective ECRHS study

Background Previous studies have reported an association between weight increase and excess lung function decline in young adults followed for short periods. We aimed to estimate lung function trajectories during adulthood from 20-year weight change profiles using data from the population-based European Community Respiratory Health Survey (ECRHS). Methods We included 3673 participants recruited at age 20–44 years with repeated measurements of weight and lung function (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1)) in three study waves (1991–93, 1999–2003, 2010–14) until they were 39–67 years of age. We classified subjects into weight change profiles according to baseline body mass index (BMI) categories and weight change over 20 years. We estimated trajectories of lung function over time as a function of weight change profiles using population-averaged generalised estimating equations. Results In individuals with normal BMI, overweight and obesity at baseline, moderate (0.25–1 kg/year) and high weight gain (>1 kg/year) during follow-up were associated with accelerated FVC and FEV1 declines. Compared with participants with baseline normal BMI and stable weight (±0.25 kg/year), obese individuals with high weight gain during follow-up had −1011 mL (95% CI −1.259 to −763) lower estimated FVC at 65 years despite similar estimated FVC levels at 25 years. Obese individuals at baseline who lost weight (<−0.25 kg/year) exhibited an attenuation of FVC and FEV1 declines. We found no association between weight change profiles and FEV1/FVC decline. Conclusion Moderate and high weight gain over 20 years was associated with accelerated lung function decline, while weight loss was related to its attenuation. Control of weight gain is important for maintaining good lung function in adult life.
Integrative Analysis Identifies Candidate Tumor Microenvironment and Intracellular Signaling Pathways that Define Tumor Heterogeneity in NF1

Neurofibromatosis type 1 is a monogenic syndrome that gives rise to numerous symptoms including cognitive impairment, skeletal abnormalities, and growth of benign nerve sheath tumors. Nearly all NF1 patients develop cutaneous neurofibromas (cNFs), which occur on the skin surface, while 40-60% of patients develop plexiform neurofibromas (pNFs) which are deeply embedded in the peripheral nerves. Patients with pNFs have a ∼10% lifetime chance of these tumors becoming malignant peripheral nerve sheath tumors (MPNSTs). These tumors have a severe prognosis and few treatment options other than surgery. Given the lack of therapeutic options available to patients with these tumors, identification of druggable pathways or other key molecular features could aid ongoing therapeutic discovery studies. In this work, we used statistical and machine learning methods to analyze 77 NF1 tumors with genomic data to characterize key signaling pathways that distinguish these tumors and identify candidates for drug development. We identified subsets of latent gene expression variables that may be important in the identification and etiology of cNFs, pNFs, other neurofibromas, and MPNSTs. Furthermore, we characterized the association between these latent variables and genetic variants, immune deconvolution predictions, and protein activity predictions.
Knockout of mouse receptor accessory protein 6 leads to sperm function and morphology defects†

Abstract Receptor accessory protein 6 (REEP6) is a member of the REEP/Ypt-interacting protein family that we recently identified as essential for normal endoplasmic reticulum homeostasis and protein trafficking in the retina of mice and humans. Interestingly, in addition to the loss of REEP6 in our knockout (KO) mouse model recapitulating the retinal degeneration of humans with REEP6 mutations causing retinitis pigmentosa (RP), we also found that male mice are sterile. Herein, we characterize the infertility caused by loss of Reep6. Expression of both Reep6 mRNA transcripts is present in the testis; however, isoform 1 becomes overexpressed during spermiogenesis. In vitro fertilization assays reveal that Reep6 KO spermatozoa are able to bind the zona pellucida but are only able to fertilize oocytes lacking the zona pellucida. Although spermatogenesis appears normal in KO mice, cauda epididymal spermatozoa have severe motility defects and variable morphological abnormalities, including bent or absent tails. Immunofluorescent staining reveals that REEP6 expression first appears in stage IV tubules within step 15 spermatids, and REEP6 localizes to the connecting piece, midpiece, and annulus of mature spermatozoa. These data reveal an important role for REEP6 in sperm motility and morphology and is the first reported function for a REEP protein in reproductive processes. Additionally, this work identifies a new gene potentially responsible for human infertility and has implications for patients with RP harboring mutations in REEP6. Summary sentence Receptor accessory protein 6 is essential for sperm motility, morphology, and penetration of the zona pellucida in mice.
PET Radiopharmaceuticals for Alzheimer’s Disease and Parkinson’s Disease Diagnosis, the Current and Future Landscape

Ironically, population aging which is considered a public health success has been accompanied by a myriad of new health challenges, which include neurodegenerative disorders (NDDs), the incidence of which increases proportionally to age. Among them, Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common, with the misfolding and the aggregation of proteins being common and causal in the pathogenesis of both diseases. AD is characterized by the presence of hyperphosphorylated τ protein (tau), which is the main component of neurofibrillary tangles (NFTs), and senile plaques the main component of which is β-amyloid peptide aggregates (Aβ). The neuropathological hallmark of PD is α-synuclein aggregates (α-syn), which are present as insoluble fibrils, the primary structural component of Lewy body (LB) and neurites (LN). An increasing number of non-invasive PET examinations have been used for AD, to monitor the pathological progress (hallmarks) of disease. Notwithstanding, still the need for the development of novel detection tools for other proteinopathies still remains. This review, although not exhaustively, looks at the timeline of the development of existing tracers used in the imaging of Aβ and important moments that led to the development of these tracers.
microRNAs in Ex Vivo Human Adipose Tissue Derived Mesenchymal Stromal Cells (ASC) Undergo Rapid Culture-Induced Changes in Expression, Including miR-378 which Promotes Adipogenesis

There is clinical interest in using human adipose tissue-derived mesenchymal stromal cells (ASC) to treat a range of inflammatory and regenerative conditions. Aspects of ASC biology, including their regenerative potential and paracrine effect, are likely to be modulated, in part, by microRNAs, small RNA molecules that are embedded as regulators of gene-expression in most biological pathways. However, the effect of standard isolation and expansion protocols on microRNA expression in ASC is not well explored. Here, by using an untouched and enriched population of primary human ASC, we demonstrate that there are rapid and significant changes in microRNA expression when ASC are subjected to standard isolation and expansion methods. Functional studies focusing on miR-378 indicate that these changes in expression may have an impact on phenotype and function. Specifically, we found that increased levels of miR-378 significantly promoted adipogenesis in late passage ASC. These results are informative to maximizing the potential of ASC for use in various clinical applications, and they have implications for targeting microRNAs as a therapeutic strategy for obesity or metabolic disease.
New use of psychotropic medication after hospitalization among people with dementia

Psychotropic medication is commonly used among people with dementia (PWD), but it shows modest efficacy and it has been associated with severe adverse events. Hospitalizations are an opportunity for medication management as well as treatment recommendations for outpatient physicians. The aim of this study was to asses factors associated with new use of psychotropic medication after hospitalization among PWD.
Evaluation of the Surface Characteristics of Dental CAD/CAM Materials after Different Surface Treatments

Computer-aided design/computer-aided manufacturing (CAD/CAM) technology was developed to ensure the sufficient strength of tooth restorations, to improve esthetic restorations with a natural appearance and to make the techniques easier, faster and more accurate. In the view of the limited research on the surface treatments of the CAD/CAM materials and the need to evaluate the ideal surface characteristics of a material to achieve the best adhesion to tooth tissues, this study aimed to investigate the surface roughness and morphology of four different CAD/CAM materials using four different surface treatments. The CAD/CAM materials used in this study were three composites (Shofu Block HC, Lava Ultimate and Brilliant Crios) and a hybrid ceramic (Enamic). The surface of the specimens of each material received one of the following treatments: no surface treatment, sandblasting with 29 μm Al2O3 particles, 9% hydrofluoric acid etching and silane application, and the tribochemical method using CoJet System. Surface roughness was evaluated using optical profilometry, and surface morphology was observed by means of scanning electron microscopy. All surface treatments resulted in higher surface roughness values compared to the control group. Different treatments affected the surface properties of the materials, presumably due to discrepancies in their composition and structure.
Composition and divergence of coronavirus spike proteins and host ACE2 receptors predict potential intermediate hosts of SARS‐CoV‐2

From the beginning of 2002 and 2012, severe respiratory syndrome coronavirus (SARS‐CoV) and Middle East respiratory syndrome coronavirus (MERS‐CoV) crossed the species barriers to infect humans, causing thousands of infections and hundreds of deaths, respectively. Currently, a novel coronavirus (SARS‐CoV‐2), which has become the cause of the outbreak of Coronavirus Disease 2019 (COVID‐19), was discovered. Until 18 February 2020, there were 72 533 confirmed COVID‐19 cases (including 10 644 severe cases) and 1872 deaths in China. SARS‐CoV‐2 is spreading among the public and causing substantial burden due to its human‐to‐human transmission. However, the intermediate host of SARS‐CoV‐2 is still unclear. Finding the possible intermediate host of SARS‐CoV‐2 is imperative to prevent further spread of the epidemic. In this study, we used systematic comparison and analysis to predict the interaction between the receptor‐binding domain (RBD) of coronavirus spike protein and the host receptor, angiotensin‐converting enzyme 2 (ACE2). The interaction between the key amino acids of S protein RBD and ACE2 indicated that, other than pangolins and snakes, as previously suggested, turtles (Chrysemys picta bellii, Chelonia mydas, and Pelodiscus sinensis) may act as the potential intermediate hosts transmitting SARS‐CoV‐2 to humans.
Enhancing α-secretase Processing for Alzheimer’s Disease—A View on SFRP1

Amyloid β (Aβ) peptides generated via sequential β- and γ-secretase processing of the amyloid precursor protein (APP) are major etiopathological agents of Alzheimer’s disease (AD). However, an initial APP cleavage by an α-secretase, such as the a disintegrin and metalloproteinase domain-containing protein ADAM10, precludes β-secretase cleavage and leads to APP processing that does not produce Aβ. The latter appears to underlie the disease symptom-attenuating effects of a multitude of experimental therapeutics in AD animal models. Recent work has indicated that an endogenous inhibitor of ADAM10, secreted-frizzled-related protein 1 (SFRP1), is elevated in human AD brains and associated with amyloid plaques in mouse AD models. Importantly, genetic or functional attenuation of SFRP1 lowered Aβ accumulation and improved AD-related histopathological and neurological traits. Given SFRP1′s well-known activity in attenuating Wnt signaling, which is also commonly impaired in AD, SFRP1 appears to be a promising therapeutic target for AD. This idea, however, needs to be addressed with care because of cancer enhancement potentials resulting from a systemic loss of SFRP1 activity, as well as an upregulation of ADAM10 activity. In this focused review, I shall discuss α-secretase-effected APP processing in AD with a focus on SFRP1, and explore the contrasting perspectives arising from the recent findings.
A new approach to cardiac fat volume assessment and the correlation with coronary artery calcification

Abstract Background. Coronary artery disease (CAD) is the foremost cause of death in the most developed societies. Plaque formation in epicardial coronary arteries and ensuing inflammation are a known pathophysiologic factor of CAD. Objectives. We aimed to separately and simultaneously evaluate the correlation between pericardial fat pad volume and overall peri-coronary epicardial adipose tissue (EAT) thickness with coronary calcium score (CCS) to improve risk stratification of CAD. Methods. We retrospectively reviewed patients who underwent a non-invasive contrast-enhanced coronary multidetector CT (MDCT) angiography. Peri-coronary EAT thickness, pericardial fat pad volume and CCS were obtained by an expert radiologist from the patients coronary multidetector CT (MDCT) angiography. Results. We included 141 symptomatic patients (86 men, 55 women) with an average age of 53.53 ± 12.92. An increment of overall peri-coronary EAT thickness (1/3 × (left anterior descending artery (LAD) + left circumflex artery (LCx) + right coronary artery (RCA)) was associated with a 49% increase in the odds for the presence of coronary artery calcification (CAC) (P = 0.004). Significant predictability of peri-coronary EAT-average was seen in diagnosing calcified plaque. Pericardial fat pad volume was positively correlated with overall peri-coronary EAT thickness in age and body mass index (BMI)-adjusted linear regression models, (P < 0.001). Conclusion. Our results amplify previous idea that peri-coronary EAT and pericardial fat pad volume might act as useful markers and better indicators of CCS based on Agatston score in comparison with BMI or body weight in order to reveal subsequent CADs.
Optimum Inhibition of Amphotericin-B-Resistant Candida albicans Strain in Single- and Mixed-Species Biofilms by Candida and Non-Candida Terpenoids

Candida albicans is one of the most common human fungal pathogens and represents the most important cause of opportunistic mycoses worldwide. Surgical devices including catheters are easily contaminated with C. albicans via its formation of drug-resistant biofilms. In this study, amphotericin-B-resistant C. albicans strains were isolated from surgical devices at an intensive care center. The objective of this study was to develop optimized effective inhibitory treatment of resistant C. albicans by terpenoids, known to be produced naturally as protective signals. Endogenously produced farnesol by C. albicans yeast and plant terpenoids, carvacrol, and cuminaldehyde were tested separately or in combination on amphotericin-B-resistant C. albicans in either single- or mixed-infections. The results showed that farnesol did not inhibit hyphae formation when associated with bacteria. Carvacrol and cuminaldehyde showed variable inhibitory effects on C. albicans yeast compared to hyphae formation. A combination of farnesol with carvacrol showed synergistic inhibitory activities not only on C. albicans yeast and hyphae, but also on biofilms formed from single- and mixed-species and at reduced doses. The combined terpenoids also showed biofilm-penetration capability. The aforementioned terpenoid combination will not only be useful in the treatment of different resistant Candida forms, but also in the safe prevention of biofilm formation.
Daily Intake of Paraprobiotic Lactobacillus amylovorus CP1563 Improves Pre-Obese Conditions and Affects the Gut Microbial Community in Healthy Pre-Obese Subjects: A Double-Blind, Randomized, Placebo-Controlled Study

Despite the fact that gut microbiota is closely associated with obesity, few studies have focused on the influences of paraprobiotics as food ingredients on both obesity prevention and the gut microbial community. In this study, we evaluated the effects of fragmented Lactobacillus amylovorus CP1563 (CP1563) as a paraprobiotic for obesity prevention and investigated its effects on the gut microbial community in pre-obese subjects. One hundred sixty-nine healthy subjects with a body mass index from 25.0 to 29.9 kg/m2 ingested beverages with or without the fragmented CP1563 containing 10-hydroxyoctadecanoic acid (10-HOA) for 12 weeks. The changes in abdominal, total, visceral, and subcutaneous fatty areas were significantly lower in the CP1563-10-HOA group than in the placebo group at 12 weeks. Furthermore, 16S rRNA gene sequencing of fecal DNA revealed that the changes in the abundances of the genera Roseburia and Lachnospiraceae;g were significantly greater in the CP1563-10-HOA group than in the placebo group, and the changes in the abundances of the genus Collinsella was significantly smaller in the CP1563-10HOA group than in the placebo group. Our results showed that continuous ingestion of the fragmented CP1563 containing 10-HOA reduced abdominal body fat and affected the gut microbial community in pre-obese healthy subjects. Our findings may contribute to the understanding of the relationship between the anti-obesity effect of paraprobiotics and gut microbiota.
Ultrastructural Dendritic Changes Underlying Diaschisis After Capsular Infarct.

Diaschisis has been described as functional depression distant to the lesion. A variety of neuroscientific approaches have been used to investigate the mechanisms underlying diaschisis. However, few studies have examined the pathological changes in diaschisis at ultrastructural level. Here, we used a rat model of capsular infarct that consistently produces diaschisis in ipsilesional and contralesional motor and sensory cortices. To verify the occurrence of diaschisis and monitor time-dependent changes in diaschisis, we performed longitudinal 2-deoxy-2-[18F]-fluoro-d-glucose microPET (FDG-microPET) study. We also used light and electron microscopy to identify the microscopic and ultrastructural changes at the diaschisis site at 7, 14, and 21 days after capsular infarct modeling (CIM). FDG-microPET showed the occurrence of diaschisis after CIM. Light microscopic examinations revealed no significant histopathological changes at the diaschisis site except a mild degree of reactive astrogliosis. However, electron microscopy revealed swollen, hydropic degeneration of axial dendrites and axodendritic synapses, although the neuronal soma (including nuclear chromatin and cytoplasmic organelles) and myelinated axons were relatively well preserved up to 21 days after injury. Furthermore, number of axodendritic synapses was significantly decreased after CIM. These data indicate that a circumscribed subcortical white-matter lesion produces ultrastructural pathological changes related to the pathogenesis of diaschisis.
Anti-Aging Effects of Leontopodium alpinum (Edelweiss) Callus Culture Extract through Transcriptome Profiling

Edelweiss (Leontopodium Alpinum) in the family Asteraceae is a wildflower that grows in rocky limestone places. Here, we investigated the efficacy of edelweiss callus culture extract (Leontopodium Alpinum callus culture extract; LACCE) using multiple assays from in vitro to in vivo as well as transcriptome profiling. Several in vitro assay results showed the strong antioxidant activity of LACCE in response to UVB treatment. Moreover, LACCE suppressed inflammation and wrinkling; however, moisturizing activity was increased by LACCE. The clinical test in vivo demonstrated that constant application of LACCE on the face and skin tissues improved anti-periorbital wrinkles, skin elasticity, dermal density, and skin thickness compared with the placebo. The RNA-Sequencing results showed at least 16.56% of human genes were expressed in keratinocyte cells. LACCE up-regulated genes encoding several KRT proteins; DDIT4, BNIP3, and IGFBP3 were involved in the positive regulation of the developmental process, programmed cell death, keratinization, and cornification forming skin barriers, which provide many advantages in the human skin. By contrast, down-regulated genes were stress-responsive genes, including metal, oxidation, wounding, hypoxia, and virus infection, suggesting LACCE did not cause any harmful stress on the skin. Our comprehensive study demonstrated LACCE is a promising agent for anti-aging cosmetics.
Sleep Apnea, Hypertension and the Sympathetic Nervous System in the Adult Population

Sleep apnea is very common in patients with cardiovascular disease, especially in patients with hypertension. Over the last few decades a number of discoveries have helped support a causal relationship between the two and even resistant hypertension. The role neurogenic mechanisms play has gathered more attention in the recent past due to their immediate bedside utility. Several innovative discoveries in pathogenesis including those exploring the role of baroreflex gain, cardiovascular variability, chemoreceptor reflex activation and the sympathetic nervous system have emerged. In this review, we discuss the epidemiology of sleep apnea and hypertension and the pathogenic mechanisms contributing to neurogenic hypertension. Furthermore, recent management strategies in addition to continuous positive airway pressure (CPAP), such as upper airway stimulation and renal denervation that target these pathogenic mechanisms, are also discussed.
Simultaneous nitrification and denitrification in continuous flow MBBR with novel surface-modified carriers

ABSTRACT Moving-Bed Biofilm Reactor (MBBR) process is an ideal preference for simultaneous nitrification and denitrification (SND) attributing to the longer sludge age and aerobic/anoxic microenvironment along biofilm. However, conventional carriers generally exhibit negative charge and surface hydrophobicity, which are unbeneficial for biofilm formation. In this study, novel surface-modified carriers with favourable hydrophilicity (surface contact angle dropped to 60.2 ± 2.3°) and positive surface charge (+11.7 ± 1.1 mV, pH 7.0) were prepared via polymer blending and implemented for SND in continuous flow MBBR system. Results indicated SND started up quickly with more biomass in MBBR filled with surface-modified carriers. At the operation condition of low dissolved oxygen level (0.75 ± 0.25 mg/L), pH of 7.5 ± 0.5, 23 ± 2°C and C/N ratio of 7, COD, NH4 +-N and TN removal efficiencies were 90.5%, 88.6% and 76.6% respectively in MBBR filled with surface-modified carriers, which ensured the effluent met the first grade A of the Discharge Standard of China. On the contrary, COD, NH4 +-N and TN removal efficiencies were 89.7%, 82.3% and 60.4% respectively in the control reactors filled with conventional polyethylene carriers. The worse performance of the control reactor was mainly attributed to the less biomass and lower functional bacteria abundance developed on conventional carriers. Moreover, novel carriers provided a favourable niche for more types of functional bacteria, of which autotrophic nitrification, anoxic denitrification, heterotrophic nitrification and aerobic denitrification co-existed and participated in nitrogen removal. GRAPHICAL ABSTRACT