Miracle-dz/UniFAR-FTUs huggingface dataset:
Regions of Low Endothelial Shear Stress Colocalize With Positive Vascular Remodeling and Atherosclerotic Plaque Disruption: An In Vivo Magnetic Resonance Imaging Study

Background— Local hemodynamic factors, particularly low endothelial shear stress (ESS), play a role in the focal formation of atherosclerosis. We used in vivo MRI to investigate the role of the magnitude of ESS on vascular remodeling, plaque burden, and disruption using a rabbit model of controlled atherothrombosis. Methods and Results— Atherosclerosis was induced in New Zealand white rabbits by cholesterol diet and endothelial denudation. MRI was performed before (pretrigger) and after (posttrigger) inducing plaque disruption with Russell viper venom and histamine. Of the 134 vascular segments studied, 28 contained thrombus (disrupted) and 106 did not (nondisrupted). Disrupted plaques were histologically characterized by a thin, inflamed fibrous cap, a dense lipid core, and mural thrombus. Pretriggered MRI revealed that disrupted plaques clustered at regions with low mean ESS (11.55±5.3 versus 20.9±9.74 dynes/cm2; P<0.001) and low peak ESS (21.5±11.2 versus 49.2±21.5 dynes/cm2; P<0.001) compared with nondisrupted plaques. The peak ESS negatively correlated with the plaque area (r=−0.56, P<0.001) and remodeling ratio (r=−0.4, P=0.008). There was also a negative correlation between the mean ESS and the remodeling ratio (r=−0.55, P<0.001). Both the peak ESS and the mean ESS did not correlate with the % stenosis; there was a weak but statistically significant correlation with the % cross-sectional narrowing (r=0.3, P=0.002 and r=0.2, P=0.04, respectively). Receiver operating characteristic analysis showed that both mean (Area under the curve=0.78; 95% CI, 0.69–0.87) and peak ESS (Area under the curve=0.85; 95% CI, 0.78–0.93) identified disrupted plaques. Conclusions— We demonstrated that low ESS is associated with plaque burden, positive vascular remodeling, and plaque disruption in a rabbit model. Assessment of ESS by noninvasive MRI might be useful for assessing atherosclerotic risk.
Seasonal trend of Anisakidae infestation in South Mediterranean bluefish

Abstract A total of 1104 fish samples from markets of Sicily were analysed for the detection and species identification of Anisakidae nematodes. The preliminary analysis of the fish samples showed the presence of 2459 larvae. All the fish species revealed different prevalence of infestation, with a maximum of 100% for Lepidopus caudatus and a minimum of 4.5% in Sardina pilchardus. The 80% of the larvae examined by PCR-RFLP analysis belonged to Anisakis pegreffii species. The seasonal infestation trend of Anisakis was evaluated in all the fish sample examined. The results of the seasonal infestation trend showed a marked connection with the ecological aspects of the fish species examined. As far as we know, this work report for the first time important ecological aspects of Lepidopus caudatus specimens of South Mediterranean. This work could be useful to plan a seasonal fishing strategy aimed at reducing the health risks related to Anisakis. Graphical Abstract
Effects of mobile phone application combined with or without self‐monitoring of blood glucose on glycemic control in patients with diabetes: A randomized controlled trial

There is potential for mobile applications to deliver new self‐management interventions for chronic disease, especially in diabetes. The aim of the present study was to evaluate the effects of a mobile phone application (MPA) combined with or without self‐monitoring of blood glucose (SMBG) on glycemic control in patients with diabetes.
Antimicrobial Resistance in Hispanic Patients Hospitalized in San Antonio, TX with Community-Acquired Pneumonia

Abstract Limited information is available on the antimicrobial resistance of patients with community-acquired pneumonia (CAP) depending on their ethnicity. Our aim was to compare the clinical characteristics, etiology, and microbiological resistance of Hispanic versus non-Hispanic white patients. A retrospective cohort of 601 patients with a diagnosis of CAP included 288 non-Hispanic whites and 313 Hispanics. Penicillin-resistant Streptococcus pneumoniae was more common among Hispanic patients (21.7% vs 0%; P = 0.03) but there were no significant differences in macrolide-resistant S pneumoniae, drug-resistant S pneumoniae, or potential or actual multidrug-resistant pathogens (eg, drug-resistant S pneumoniae, methicillin-resistant Staphylococcus aureus, Pseudomonas spp., and Acinetobacter spp.). There were no differences among groups in length of hospital stay, intensive care unit (ICU) admission, or 30-day mortality. This study suggests that Hispanic patients with CAP have a higher rate of penicillin-resistant S pneumoniae, but no differences in antimicrobial resistance, 30-day mortality, ICU admission, or length of stay when compared with non-Hispanic white patients.
Intestinal Permeation Enhancers for Oral Delivery of Macromolecules: A Comparison between Salcaprozate Sodium (SNAC) and Sodium Caprate (C10)

Salcaprozate sodium (SNAC) and sodium caprate (C10) are two of the most advanced intestinal permeation enhancers (PEs) that have been tested in clinical trials for oral delivery of macromolecules. Their effects on intestinal epithelia were studied for over 30 years, yet there is still debate over their mechanisms of action. C10 acts via openings of epithelial tight junctions and/or membrane perturbation, while for decades SNAC was thought to increase passive transcellular permeation across small intestinal epithelia based on increased lipophilicity arising from non-covalent macromolecule complexation. More recently, an additional mechanism for SNAC associated with a pH-elevating, monomer-inducing, and pepsin-inhibiting effect in the stomach for oral delivery of semaglutide was advocated. Comparing the two surfactants, we found equivocal evidence for discrete mechanisms at the level of epithelial interactions in the small intestine, especially at the high doses used in vivo. Evidence that one agent is more efficacious compared to the other is not convincing, with tablets containing these PEs inducing single-digit highly variable increases in oral bioavailability of payloads in human trials, although this may be adequate for potent macromolecules. Regarding safety, SNAC has generally regarded as safe (GRAS) status and is Food and Drug Administration (FDA)-approved as a medical food (Eligen®-Vitamin B12, Emisphere, Roseland, NJ, USA), whereas C10 has a long history of use in man, and has food additive status. Evidence for co-absorption of microorganisms in the presence of either SNAC or C10 has not emerged from clinical trials to date, and long-term effects from repeat dosing beyond six months have yet to be assessed. Since there are no obvious scientific reasons to prefer SNAC over C10 in orally delivering a poorly permeable macromolecule, then formulation, manufacturing, and commercial considerations are the key drivers in decision-making.
Extent of Inflammation and Foreign Body Reaction to Porous Polyethylene In Vitro and In Vivo

Background/Aim: High-density porous polyethylene (PP) offers possibilities for reconstruction in craniofacial surgery. The purpose of this study was to evaluate the extent of inflammation and foreign body reactions to PP in vitro and in vivo. Materials and Methods: Cell attachment, proliferation and expression of inflammatory cytokines were assessed using murine macrophages (RAW 264.7) on two different PP materials in vitro. In vivo, Balb/c mice received PP implants at their dorsum. After sacrifice, samples were analyzed histologically and real-time PCR was used to assess expression of inflammatory cytokines. Results: Cells showed a significantly decreased proliferation (p<0.001) after 48 h and a significantly increased expression of TNF-α (p<0.05) at 24, 48 and 72 h. All animals showed foreign body cell reactions and signs of chronic inflammation. Expression of all but one of the investigated cytokines dropped to non-significant levels after an initial increase. Conclusion: Application of porous polyethylene can cause local chronic inflammatory reactions. Although clinical application seems to be immunologically safe, indication and risks should be evaluated carefully when using PP implants.
Education and Income Levels are Associated With Energy and Micronutrients Intake.

INTRODUCTION According to the literature, education and income are determinants factors of diet quality and consequently of micronutrient intake. However, this association is still little known among adults who live in middle-income countries. OBJECTIVE To estimate energy and micronutrients intake by men and women living in a capital city in southern Brazil, according to education and income levels, and to identify prevalence of inadequate micronutrient intake according also to education and income levels. METHOD This is a second wave cross-sectional analysis of a population-based longitudinal study, the EpiFloripa Adultos, including 1,222 individuals of 22-63 years. Data on food consumption were obtained through applying two 24-hour dietary recalls, and the prevalence of inadequate micronutrient intake, following the recommendations of the Institute of Medicine and from the National Research Council. RESULTS A tendency of increased intake with an increase in income (calcium, vitamins C, E) and education levels (calcium, vitamins A, C, D) was observed for most of the micronutrients analyzed (p<0.05 in all cases); still, a prevalence of inadequacy according to Estimated Average Requirement (EAR) between 85.5-100% in intake of vitamins A, D and E were found for the whole sample. Iron inadequate intake was associated with education level and among women less than 50 years of age (p=0.018). CONCLUSION The results showed an influence of the education and income levels on micronutrient intake, point to the need of daily food consumption, of minimally processed and in natura foods (as fruits, vegetables, whole grains, milk and its derivatives) as a means to reduce the encountered inadequacies.
Celebrating science's next generation

Drum roll, please . It’s time to announce the 2019 group of Herbert Tabor Young Investigator Awardees! Devoted readers of our editorials will know that we recently decided to refocus these awards on the first authors of some of the best work appearing in JBC (1), and we were thrilled to honor the first group of these rising stars in writing (2) and in person at last year’s ASBMB annual meeting. This past fall, we again asked for your help (3) in identifying the most exciting and influential papers published in JBC in 2018 to make sure we were not overlooking any potential awardees. We are so grateful for the many of you who took the time to share your thoughts, both for the specific suggestions made and for the continued demonstration that the biological chemistry community values the contributions of and ideas brewing in this new generation of scientists. Along those lines, we have two additional announcements to share with you. First, we know that not all “new” scientists are “young,” and we want to be explicit that we also value those researchers who’ve come to science later in their lives. As such, future iterations of this award will be known as the “Herbert Tabor Early Career Investigator Award. ” Second, we know that the challenges faced by early career scientists cannot all be solved with a single award. As a result, we have spent time in the last two years talking with early career scientists about what JBC can do to most effectively support the next generation of scientists. We have been piloting an “early career reviewer” system, layered on top of our existing review process, and there are other ideas on the table. We have recently created a committee dedicated to turning ideas into actions and are eager for more input and engagement with early career investigators. If you are an early career scientist, please e-mail jbc@asbmb.org to let us know what you see as the most critical challenges you face, with any suggestions for how JBC can support you, or to be considered as an early career reviewer or for other upcoming initiatives.
Mechanisms of Spindle Positioning: Lessons from Worms and Mammalian Cells

Proper positioning of the mitotic spindle is fundamental for specifying the site for cleavage furrow, and thus regulates the appropriate sizes and accurate distribution of the cell fate determinants in the resulting daughter cells during development and in the stem cells. The past couple of years have witnessed tremendous work accomplished in the area of spindle positioning, and this has led to the emergence of a working model unravelling in-depth mechanistic insight of the underlying process orchestrating spindle positioning. It is evident now that the correct positioning of the mitotic spindle is not only guided by the chemical cues (protein–protein interactions) but also influenced by the physical nature of the cellular environment. In metazoans, the key players that regulate proper spindle positioning are the actin-rich cell cortex and associated proteins, the ternary complex (Gα/GPR-1/2/LIN-5 in Caenorhabditis elegans, Gαi/Pins/Mud in Drosophila and Gαi1-3/LGN/NuMA in humans), minus-end-directed motor protein dynein and the cortical machinery containing myosin. In this review, I will mainly discuss how the abovementioned components precisely and spatiotemporally regulate spindle positioning by sensing the physicochemical environment for execution of flawless mitosis.
Heart disease and stroke statistics--2011 update: a report from the American Heart Association.

Véronique L. Roger, MD, MPH, FAHA; Alan S. Go, MD; Donald M. Lloyd-Jones, MD, ScM, FAHA; Robert J. Adams, MD, MS, FAHA; Jarett D. Berry, MD; Todd M. Brown, MD, MSPH; Mercedes R. Carnethon, PhD, FAHA; Shifan Dai, MD, PhD*; Giovanni de Simone, MD, FAHA; Earl S. Ford, MD, MPH, FAHA*; Caroline S. Fox, MD, MPH; Heather J. Fullerton, MD; Cathleen Gillespie, MS*; Kurt J. Greenlund, PhD*; Susan M. Hailpern, DPH, MS; John A. Heit, MD, FAHA; P. Michael Ho, MD, PhD; Virginia J. Howard, PhD, FAHA; Brett M. Kissela, MD; Steven J. Kittner, MD, FAHA; Daniel T. Lackland, DrPH, MSPH, FAHA; Judith H. Lichtman, PhD, MPH; Lynda D. Lisabeth, PhD, FAHA; Diane M. Makuc, DrPH*; Gregory M. Marcus, MD, MAS, FAHA; Ariane Marelli, MD; David B. Matchar, MD, FAHA; Mary M. McDermott, MD; James B. Meigs, MD, MPH; Claudia S. Moy, PhD, MPH; Dariush Mozaffarian, MD, DrPH, FAHA; Michael E. Mussolino, PhD; Graham Nichol, MD, MPH, FAHA; Nina P. Paynter, PhD, MHSc; Wayne D. Rosamond, PhD, FAHA; Paul D. Sorlie, PhD; Randall S. Stafford, MD, PhD, MHS, FAHA; Tanya N. Turan, MD, FAHA; Melanie B. Turner, MPH; Nathan D. Wong, PhD, MPH, FAHA; Judith Wylie-Rosett, EdD, RD; on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee
Redox transients of P680 associated with the incremental chlorophyll-a fluorescence yield rises elicited by a series of saturating flashes in diuron-treated photosystem II core complex of Thermosynechococcus vulcanus.

Recent chlorophyll-a fluorescence yield measurements, using single-turnover saturating flashes (STSFs), have revealed the involvement of a rate-limiting step in the reactions following the charge separation induced by the first flash. As also shown here, in diuron-inhibited PSII core complexes isolated from Thermosynechococcus vulcanus the fluorescence maximum could only be reached by a train of STSFs. In order to elucidate the origin of the fluorescence yield increments in STSF series, we performed transient absorption measurements at 819 nm, reflecting the photooxidation and re-reduction kinetics of the primary electron donor P680. Upon single flash excitation of the dark-adapted sample, the decay kinetics could be described with lifetimes of 17 ns (∼50%) and 167 ns (∼30%), and a longer-lived component (∼20%). This kinetics are attributed to re-reduction of P680•+ by the donor side of PSII. In contrast, upon second-flash (with Δt between 5 μs and 100 ms) or repetitive excitation, the 819 nm absorption changes decayed with lifetimes of about 2 ns (∼60%) and 10 ns (∼30%), attributed to recombination of the primary radical pair P680•+ Pheo•- , and a small longer-lived component (∼10%). These data confirm that only the first STSF is capable of generating stable charge separation - leading to the reduction of QA ; and thus, the fluorescence yield increments elicited by the consecutive flashes must have a different physical origin. Our double-flash experiments indicate that the rate-limiting steps, detected by chlorophyll-a fluorescence, are not correlated with the turnover of P680.
Imaging Characteristics of Liver Metastases Overlooked at Contrast-Enhanced CT.

OBJECTIVE The purpose of this study was to evaluate the imaging characteristics of liver metastases overlooked at contrast-enhanced CT. MATERIALS AND METHODS The records of 746 patients with a diagnosis of liver metastases from colorectal, breast, gastric, or lung cancer between November 2010 and September 2017 were reviewed. Images were reviewed when liver metastases were first diagnosed, and images from prior contrast-enhanced CT examinations were checked if available. These lesions were classified into two groups: missed lesions (those missed on the prior images) and detected lesions (those correctly identified and invisible on the prior images or there were no prior images). Tumor size, contrast-to-noise ratio, location, presence of coexisting liver cysts and hepatic steatosis, and indications for examination were compared between the groups. The t test and Fisher exact test were used to analyze the imaging characteristics of previously overlooked lesions. RESULTS The final analysis included 137 lesions, of which 68 were classified as missed. In univariate analysis, contrast-to-noise ratio was significantly lower in missed lesions (95% CI, 2.65 ± 0.24 vs 3.90 ± 0.23; p < 0.001). The proportion of subcapsular lesions (odds ratio, 3.44; p < 0.001), hepatic steatosis (odds ratio, 6.35; p = 0.007), and examination indication other than survey of malignant tumors (odds ratio, 9.07; p = 0.02) were significantly higher for missed lesions. CONCLUSION Liver metastases without sufficient contrast enhancement, those in patients with hepatic steatosis, those in subcapsular locations, and those found at examinations for indications other than to assess for tumors were significantly more likely to be overlooked.
Redox Imbalance in Idiopathic Pulmonary Fibrosis: A Role for Oxidant Cross-Talk Between NADPH Oxidase Enzymes and Mitochondria.

SIGNIFICANCE Idiopathic pulmonary fibrosis (IPF) is a progressive age-related lung disease with a median survival of only 3 years after diagnosis. The pathogenic mechanisms behind IPF are not clearly understood, and current therapeutic approaches have not been successful in improving disease outcomes. Recent Advances: IPF is characterized by increased production of reactive oxygen species (ROS), primarily by NADPH oxidases (NOXes) and mitochondria, as well as altered antioxidant defenses. Recent studies have identified the NOX isoform NOX4 as a key player in various important aspects of IPF pathology. In addition, mitochondrial dysfunction is thought to enhance pathological features of IPF, in part by increasing mitochondrial ROS (mtROS) production and altering cellular metabolism. Recent findings indicate reciprocal interactions between NOX enzymes and mitochondria, which affect regulation of NOX activity as well as mitochondrial function and mtROS production, and collectively promote epithelial injury and profibrotic signaling. Critical Issues and Future Directions: The precise molecular mechanisms by which ROS from NOX or mitochondria contribute to IPF pathology are not known. This review summarizes the current knowledge with respect to the various aspects of ROS imbalance in the context of IPF and its proposed roles in disease development, with specific emphasis on the importance of inappropriate NOX activation, mitochondrial dysfunction, and the emerging evidence of NOX-mitochondria cross-talk as important drivers in IPF pathobiology.
Variety Is the Spice of Late Life: Social Integration and Daily Activity.

OBJECTIVES Social integration (involvement with a diverse array of social ties) has been linked to positive outcomes including better physical health. Research has not investigated whether encounters with diverse social ties enhance individuals' daily behaviors. The objectives of this study were to assess whether social ties connect individuals to more diverse daily behaviors, physical activity, and nonsedentary time as well as more positive mood. METHOD Older adults (aged 65+, n = 313) provided information about their 10 closest social ties. Then they completed ecological momentary assessment (EMA) surveys every 3 hr for 5-6 days where they reported on social encounters and behaviors. They also wore Actical accelerometers to objectively measure physical activity. RESULTS Multilevel models revealed that encounters with a greater variety of social ties was associated with engaging in a greater variety of behaviors, more objectively measured physical activity, and a smaller proportion of time spent sedentary. Encounters with weak ties/peripheral social ties accounted for this increased activity (compared to being alone or with close friends or family). Moreover, involvement with diverse ties or diverse behaviors was associated with better mood. DISCUSSION Findings are discussed in terms of social engagement theory, network diversity, and the benefits of weak ties.
Memory and CAR‐NK cell‐based novel approaches for HIV vaccination and eradication

Human immunodeficiency virus (HIV) is one of the critical infectious agents with thousands of newly infected people worldwide. High mutational capability and rapid diversification, inhibition of humoral and cellular immune responses, and thus inability for recognition of an immunogenic region in the viral envelope by the immune system are major challenges. Natural killer (NK) cells are multifunctional, playing a key role in the identification and elimination of HIV‐infected cells. These cells identify and eliminate virus‐infected cells in a multilateral manner, such as ligand stress, antibody‐dependent cell cytotoxicity (ADCC), T follicular helper (Tfh), and the activation of most of the stimulatory receptors. Moreover, these cells release cytokines leading to the activation of cytotoxic lymphocytes (CTLs) and dendritic cells (DCs), contributing to efficient viral elimination. Some subsets of NK cells exhibit putatively enhanced effector functions against viruses following vaccination easily expanded and identified by NK cell lines culture. Furthermore, NK cells promote the elimination of HIV‐infected cells which reduce the expression of major histocompatibility complex (MHC) molecules. Memory NK cells have higher functionality and renewable potential. A pioneering strategy to establish an efficacious HIV vaccine would include stimulation of the accumulation and long‐term maintenance of these HIV‐reactive NK cells. CAR‐NK (chimeric antigen receptor‐natural killer) cells‐based antiviral therapies have emerged as novel approaches with the ability of antigen recognition and more advantages than CAR‐T (chimeric antigen receptor‐T) cells. Recent development of induced pluripotent stem cell (iPSC)‐derived NK cells with enhanced activity and efficiency conferred a promising insight into CAR‐NK cell‐based therapies. Therefore, memory and CAR‐NK cells‐based approaches can emerge as novel strategies providing implications for HIV vaccine design and therapy.