Miracle-dz/UniFAR-FTUs huggingface dataset:
Physical Activity, Brain Volume, and Dementia Risk: The Framingham Study

Background Several longitudinal studies found an inverse relationship between levels of physical activity and cognitive decline, dementia, and/or Alzheimer's disease (AD), but results have been inconsistent. We followed an older, community-based cohort for over a decade to examine the association of physical activity with the risk of incident dementia and subclinical brain MRI markers of dementia. Methods The physical activity index (PAI) was assessed in the Framingham Study Original and Offspring cohorts, aged 60 years or older. We examined the association between PAI and risk of incident all-cause dementia and AD in participants of both cohorts who were cognitively intact and had available PAI (n = 3,714; 54% women; mean age = 70±7 years). We additionally examined the association between PAI and brain MRI in the Offspring cohort (n = 1,987). Results Over a decade of follow-up, 236 participants developed dementia (188 AD). Participants in the lowest quintile of PAI had an increased risk of incident dementia compared with those in higher quintiles (hazard ratio [HR] = 1.50, 95% confidence interval [CI] = 1.04-1.97, p = .028) in a multivariable-adjusted model. Secondary analysis revealed that this relation was limited to participants who were apolipoprotein (APO)E ε4 allele noncarriers (HR = 1.58, 95% CI = 1.08-2.32; p = .018) and strongest in participants aged 75 years or older. PAI was also linearly related to total brain and hippocampal volumes (β ± SE = 0.24±0.06; p < .01 and 0.004±0.001; p = .003, respectively). Conclusion Low physical activity is associated with a higher risk for dementia in older individuals, suggesting that a reduced risk of dementia and higher brain volumes may be additional health benefits of maintaining physical activity into old age.
Habits and beliefs related to food supplements: Results of a survey among Italian students of different education fields and levels

The increasing availability of food supplements, aggressive media advertising, and common beliefs that these substances have only positive effects on health and sport performance indicate a need for continuous monitoring of this phenomenon. The aim of this study was to investigate the habits and beliefs related to diet supplementation among medical, health professional, and other university/high school students by means of a cross-sectional anonymous survey online. Among the respondents aware of supplements, 37.4% were taking or had taken them in the past. Food supplement use was more common among university students (in particular, those in health professional graduate courses) than high school students. Individual sport practice, rather than team sport, was associated with higher likelihood of food supplement use. Multivitamins were most commonly used, while weight-loss formulations were the least popular. Strikingly, filling nutrient gaps was statistically not considered the main reason for taking food supplements. Instead, they were used to enhance mental performance or enhance well-being. There was statistical evidence that students not enrolled in health or medical professional studies strongly agreed more often than medical students that taking food supplements prevents illness. These results indicate a striking difference between the evidence-based and personal reasons for food supplement use. Arguably, it calls for an improvement in education about diet supplementation and a change in attitude of health care providers to its implementation.
Female-to-Male Gender Affirming Top Surgery: A Single Surgeon’s 15-Year Retrospective Review and Treatment Algorithm

Background Mastectomy, referred to here as "Top Surgery," is an important surgical step for female-to-male (FTM) transgender patients. The goal is to excise breast tissue and create a masculine chest contour. Despite the rising demand for Top Surgery, debate still exists regarding how to select the most appropriate surgical technique to optimize aesthetic outcomes safely. Objectives To determine the safety profile and aesthetic outcome of one surgeon's 15-year FTM Top Surgery experience. To provide an algorithm for FTM surgery technique selection based on this experience. Methods A retrospective chart review was performed on 679 FTM patients (1358 mastectomies) undergoing Top Surgery from October 2001 to July 2016. The author's Top Surgery algorithm utilizes two techniques, "Keyhole" and "Double Incision Free Nipple Graft (DIFNG)," based on breast ptosis, inferior vertical skin pinch, and skin elasticity. Demographic data, operative details, complications, and reoperations along with their reasons were collected and analyzed. Results Of the 679 patients, 15.3% underwent Keyhole and the remaining 84.7% underwent DIFNG procedure. The total complication rate was 18.1% and the total reoperation rate was 11.2% and these rates were shown to decrease over time. The two techniques differed significantly (P < 0.001) in operating time (136 vs 102 min), breast weight excised (215 vs 638 g), and complication rate (33 vs 16%). The aesthetic rating of results was 4.6/5 for Keyhole and 3.7/5 for DIFNG. Conclusions Safe and aesthetically pleasing results were achieved using this simplified algorithm. Experience with FTM techniques can decrease complication and reoperation rates over time. Level of Evidence 3.
Modular experimental setup for real‐time analysis of emergent behavior in networks of Chua's circuits

This paper describes the design, realization and use of an analogical, fully reconfigurable experimental setup to analyze the complex dynamics of networks of chaotic circuits. It reports details of the implementation and characterization of the setup, together with representative results, showing its flexibility and potential. The setup allows to choose arbitrarily the coupling strength and interconnection structure among the circuits, the type of link and to select the parameters of the node dynamics. It has a modular structure, and it can accommodate up to 32 nodes interconnected by at most 32 links. The collective dynamics of a relatively large set of different network structures and configurations has been investigated using the setup. Synchronization, pattern formation and other interesting collective phenomena were observed experimentally, their evidence being reported here as an illustration of the potential of the proposed setup. Copyright © 2015 John Wiley & Sons, Ltd.
Programmed Death-1 Pathway in Orbital Invasion of Cutaneous Carcinomas.

PURPOSE The programmed death-1 pathway negatively regulates the immune system. Previous reports have indicated worse tumor-related outcomes with increased expression of the ligand for this pathway. This study was undertaken to assess the role of the PD pathway in cutaneous malignancies that invade the orbit. METHODS Immunohistochemical staining for the programmed death-1 receptor and ligand was performed on exenteration specimens of invasive cutaneous orbital malignancies (n = 12) and nodular basal cell carcinoma (n = 10). The numbers of positively-staining cells/40× field were counted across 5 consecutive fields, and statistical analyses were performed to compare the differences between the 2 groups. RESULTS Programmed death-1 receptor positivity was seen in means of 30.9 cells/40× field and 62.4 cells/40× field for nodular basal cell carcinomas and invasive malignancies, respectively (p = 0.0046). A mean of 4.54 cells/40× field stained positively for the programmed death-1 ligand in nodular basal cell carcinoma, whereas a mean of 46.4 cells/40× field stained positively for programmed cell death ligand-1 in orbital invasive cutaneous carcinomas (p = 0.0015). Both of these differences were statistically significant. CONCLUSIONS Both the programmed death-1 receptor and its ligand are enriched in invasive cutaneous malignancies. This finding indicates that negative regulation of the immune system likely prohibits tumor surveillance, and facilitates increasing aggressiveness and invasion of cutaneous malignancies.
Intercomparison methods for satellite measurements of atmospheric composition: application to tropospheric ozone from TES and OMI

Abstract. We analyze the theoretical basis of three different methods to validate and intercompare satellite measurements of atmospheric composition, and apply them to tropospheric ozone retrievals from the Tropospheric Emission Spectrometer (TES) and the Ozone Monitoring Instrument (OMI). The first method (in situ method) uses in situ vertical profiles for absolute instrument validation; it is limited by the sparseness of in situ data. The second method (CTM method) uses a chemical transport model (CTM) as an intercomparison platform; it provides a globally complete intercomparison with relatively small noise from model error. The third method (averaging kernel smoothing method) involves smoothing the retrieved profile from one instrument with the averaging kernel matrix of the other; it also provides a global intercomparison but dampens the actual difference between instruments and adds noise from the a priori. We apply the three methods to a full year (2006) of TES and OMI data. Comparison with in situ data from ozonesondes shows mean positive biases of 5.3 parts per billion volume (ppbv) (10%) for TES and 2.8 ppbv (5%) for OMI at 500 hPa. We show that the CTM method (using the GEOS-Chem CTM) closely approximates results from the in situ method while providing global coverage. It reveals that differences between TES and OMI are generally less than 10 ppbv (18%), except at northern mid-latitudes in summer and over tropical continents. The CTM method further allows for CTM evaluation using both satellite observations. We thus find that GEOS-Chem underestimates tropospheric ozone in the tropics due to possible underestimates of biomass burning, soil, and lightning emissions. It overestimates ozone in the northern subtropics and southern mid-latitudes, likely because of excessive stratospheric influx of ozone.
Bilateral Rolandic operculum processing underlying heartbeat awareness reflects changes in bodily self‐consciousness

Exteroceptive bodily signals (including tactile, proprioceptive and visual signals) are important information contributing to self‐consciousness. Moreover, prominent theories proposed that visceral signals about internal bodily states are equally or even more important for self‐consciousness. Neuroimaging studies have described several brain regions which process signals related to bodily self‐consciousness (BSC) based on the integration of exteroceptive signals (e.g. premotor cortex, angular gyrus, supramarginal gyrus and extrastriate body area), and that another brain region, the insula/operculum which is involved in interoception and interoceptive awareness, processes signals critical for self‐awareness. Providing evidence for the integration of exteroceptive and interoceptive bodily signals, recent behavioral experiments have demonstrated that the manipulation of interoceptive (e.g. cardiac) signals, coupled with exteroceptive (e.g. visual) signals, also modulates BSC. Does this integration occur within or outside the structures described above? To this end, we adapted a recently designed protocol that uses cardio‐visual stimulation to induce altered states of BSC to fMRI. Additionally, we measured neural activity in a classical interoceptive task. We found six brain regions (bilateral Rolandic operculum, bilateral supramarginal gyrus, right frontal inferior operculum and left temporal superior gyrus) that were activated differently during the interoception task as opposed to a control task. The brain regions which showed the highest selectivity for BSC based on our cardio‐visual manipulation were found in the bilateral Rolandic operculum. Given our findings, we propose that the Rolandic operculum processes integrated exteroceptive–interoceptive signals that are necessary for interoceptive awareness as well as BSC.
Isolation and characterization of buffalo (bubalus bubalis) amniotic mesenchymal stem cells derived from amnion from the first trimester pregnancy

Amniotic mesenchymal stem cells (AMSCs) from livestock are valuable resources for animal reproduction and veterinary therapeutic. The purpose of this study is to explore a suitable way to isolate and culture the buffalo AMSCs (bAMSCs), and to identify their biological characteristics. Digestion with a combination of trypsin-EDTA and collagenase type I could obtain pure bAMSCs more effectively than trypsin-EDTA or collagenase type I alone. bAMSCs could proliferate steadily in vitro culture and exhibited fibroblastic-like morphology in vortex-shaped colony. bAMSCs were positive for MSC-specific markers CD44, CD90, CD105, CD73, β-integrin (CD29) and CD166, and pluripotent markers OCT4, SOX2, NANOG, REX-1, SSEA-1, SSEA-4 and TRA-1-81, but negative for hematopoietic markers CD34, CD45 and epithelial cells specific marker Cytokeratin 18. In addition, bAMSCs were capable of differentiating into adipogenic, osteogenic, chondrogenic and neural lineages, with expression of FABP4, Ost, ACAN, COL2A1, Nestin and β III-tubulin. Glycogen synthase kinase 3 inhibitor: kenpaullone promoted bAMSCs to differentiate into neural lineage. This study provides an effective protocol to obtain and characterize bAMSCs, which have proven useful as a cell resource for buffalo cell reprogramming studies and transgenic animal production.
Reoxidation of the Thiol-Disulfide Oxidoreductase MdbA by a Bacterial Vitamin K Epoxide Reductase in the Biofilm-Forming Actinobacterium Actinomyces oris

ABSTRACT Posttranslocational protein folding in the Gram-positive biofilm-forming actinobacterium Actinomyces oris is mediated by a membrane-bound thiol-disulfide oxidoreductase named MdbA, which catalyzes oxidative folding of nascent polypeptides transported by the Sec translocon. Reoxidation of MdbA involves a bacterial vitamin K epoxide reductase (VKOR)-like protein that contains four cysteine residues, C93/C101 and C175/C178, with the latter forming a canonical CXXC thioredoxin-like motif; however, the mechanism of VKOR-mediated reoxidation of MdbA is not known. We present here a topological view of the A. oris membrane-spanning protein VKOR with these four exoplasmic cysteine residues that participate in MdbA reoxidation. Like deletion of the VKOR gene, alanine replacement of individual cysteine residues abrogated polymicrobial interactions and biofilm formation, concomitant with the failure to form adhesive pili on the bacterial surface. Intriguingly, the mutation of the cysteine at position 101 to alanine (C101A mutation) resulted in a high-molecular-weight complex that was positive for MdbA and VKOR by immunoblotting and was absent in other alanine substitution mutants and the C93A C101A double mutation and after treatment with the reducing agent β-mercaptoethanol. Consistent with this observation, affinity purification followed by immunoblotting confirmed this MdbA-VKOR complex in the C101A mutant. Furthermore, ectopic expression of the Mycobacterium tuberculosis VKOR analog in the A. oris VKOR deletion (ΔVKOR) mutant rescued its defects, in contrast to the expression of M. tuberculosis VKOR variants known to be nonfunctional in the disulfide relay that mediates reoxidation of the disulfide bond-forming catalyst DsbA in Escherichia coli. Altogether, the results support a model of a disulfide relay, from its start with the pair C93/C101 to the C175-X-X-C178 motif, that is required for MdbA reoxidation and appears to be conserved in members of the class Actinobacteria. IMPORTANCE It has recently been shown in the high-GC Gram-positive bacteria (or Actinobacteria) Actinomyces oris and Corynebacterium diphtheriae that oxidative folding of nascent polypeptides transported by the Sec machinery is catalyzed by a membrane-anchored oxidoreductase named MdbA. In A. oris, reoxidation of MdbA requires a bacterial VKOR-like protein, and yet, how VKOR mediates MdbA reoxidation is unknown. We show here that the A. oris membrane-spanning protein VKOR employs two pairs of exoplasmic cysteine residues, including the canonical CXXC thioredoxinlike motif, to oxidize MdbA via a disulfide relay mechanism. This mechanism of disulfide relay is essential for pilus assembly, polymicrobial interactions, and biofilm formation and appears to be conserved in members of the class Actinobacteria, including Mycobacterium tuberculosis.
Place‐based and data‐rich citizen science as a precursor for conservation action

Environmental education strategies have customarily placed substantial focus on enhancing ecological knowledge and literacy with the hope that, upon discovering relevant facts and concepts, participants will be better equipped to process and dissect environmental issues and, therefore, make more informed decisions. The assumption is that informed citizens will become active citizens––enthusiastically lobbying for, and participating in, conservation‐oriented action. We surveyed and interviewed and used performance data from 432 participants in the Coastal Observation and Seabird Survey Team (COASST), a scientifically rigorous citizen science program, to explore measurable change in and links between understanding and action. We found that participation in rigorous citizen science was associated with significant increases in participant knowledge and skills; a greater connection to place and, secondarily, to community; and an increasing awareness of the relative impact of anthropogenic activities on local ecosystems specifically through increasing scientific understanding of the ecosystem and factors affecting it. Our results suggest that a place‐based, data‐rich experience linked explicitly to local, regional, and global issues can lead to measurable change in individual and collective action, expressed in our case study principally through participation in citizen science and community action and communication of program results to personal acquaintances and elected officials. We propose the following tenets of conservation literacy based on emergent themes and the connections between them explicit in our data: place‐based learning creates personal meaning making; individual experience nested within collective (i.e., program‐wide) experience facilitates an understanding of the ecosystem process and function at local and regional scales; and science‐based meaning making creates informed concern (i.e., the ability to discern both natural and anthropogenic forcing), which allows individuals to develop a personalized prioritization schema and engage in conservation action.
Learning from the design, development and implementation of the Medication Safety Thermometer

Abstract Quality issue Approximately 10% of patients are harmed by healthcare, and of this harm 15% is thought to be medication related. Despite this, medication safety data used for improvement purposes are not often routinely collected by healthcare organizations over time. Initial assessment A need for a prospective medication safety measurement tool was identified. Choice of solution The aim was to develop a tool to allow measurement and aid improvement of medication safety over time. The methodology used for the National Health Service (NHS) Safety Thermometer was identified as an approach. The resulting tool was named the ‘Medication Safety Thermometer’. Implementation The development of the Medication Safety Thermometer was facilitated by a multidisciplinary steering group using a Plan, Do, Study, Act (PDSA) method. Alpha and beta testing occurred over a period of 9 months. The tool was officially launched in October 2013 and continued to be improved until May 2016 using ongoing user feedback. Evaluation Feedback was gained through paper and online forms, and was discussed at regular steering group meetings. This resulted in 16 versions of the tool. The tool is now used nationally, with over 230 000 patients surveyed in over 100 NHS organizations. Data from these organizations are openly accessible on a dedicated website. Lessons learned Measuring harm from medication errors is complex and requires steps to measure individual errors, triggers of harm and actual harm. PDSA methodology can be effectively used to develop measurement systems. Measurement at the point of care is beneficial and a multidisciplinary approach is vital.
Incremental prognostic value of coronary computed tomography angiography over coronary calcium scoring for major adverse cardiac events in elderly asymptomatic individuals

Abstract Aims Coronary computed tomography angiography (CCTA) and coronary artery calcium score (CACS) have prognostic value for coronary artery disease (CAD) events beyond traditional risk assessment. Age is a risk factor with very high weight and little is known regarding the incremental value of CCTA over CAC for predicting cardiac events in older adults. Methods and results Of 27 125 individuals undergoing CCTA, a total of 3145 asymptomatic adults were identified. This study sample was categorized according to tertiles of age (cut-off points: 52 and 62 years). CAD severity was classified as 0, 1–49, and ≥50% maximal stenosis in CCTA, and further categorized according to number of vessels ≥50% stenosis. The Framingham 10-year risk score (FRS) and CACS were employed as major covariates. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause death or non-fatal MI. During a median follow-up of 26 months (interquartile range: 18–41 months), 59 (1.9%) MACE occurred. For patients in the top age tertile, CCTA improved discrimination beyond a model included FRS and CACS (C-statistic: 0.75 vs. 0.70, P-value = 0.015). Likewise, the addition of CCTA improved category-free net reclassification (cNRI) of MACE in patients within the highest age tertile (e.g. cNRI = 0.75; proportion of events/non-events reclassified were 50 and 25%, respectively; P-value <0.05, all). CCTA displayed no incremental benefit beyond FRS and CACS for prediction of MACE in the lower age tertiles. Conclusion CCTA provides added prognostic value beyond cardiac risk factors and CACS for the prediction of MACE in asymptomatic older adults.
Catheter ablation of atrial fibrillation in very young adults: a 5-year follow-up study

Aims Catheter ablation is an established therapy for symptomatic atrial fibrillation (AF). However, outcome data on catheter ablation for AF in young adults is scarce. Methods and results From 2005-2014, 85 consecutive young adults (mean age 31 ± 4 years; 69% men) with symptomatic paroxysmal AF (PAF, n = 52) and persistent (Pers) AF (n = 33) underwent pulmonary vein isolation (PVI) [±ablation of complex fractionated atrial electrograms/linear lesions in PVI non-responders] at our centre. Follow-up was based on outpatient visits including 24-h Holter-ECG at 3, 6 and, 12 months post ablation, and every 12 months thereafter. Recurrence was defined as any AF/atrial tachycardia episode >30s following a 3-month blanking period. Follow-up was available for 74/85 (87%) patients. After a median follow-up of 4.6 years (Q1: 2.6; Q3: 6.6) and a mean of 1.5 ± 0.6 (median 1, range 1-3) ablation procedures 84% [including 13% on previously ineffective antiarrhythmic drugs (AAD)] of patients were in stable SR. Single-procedural 1-year/5-year arrhythmia-free survival was 66% [95% confidence interval (CI): 56-78%]/44% (95% CI: 33-59%), respectively. Structural heart disease [SHD; hazard ratio (HR) 2.79 (95% CI 1.52-5.12), P = 0.001] and obesity [HR 1.10 (95% CI 1.00-1.21) per unit increase in body mass index >27 kg/m2, P = 0.05] independently predicted AF recurrence. Major complications occurred in 6/122 (4.9%) procedures (PV stenosis in 3, cardiac tamponade in 1, stroke in 1, and arterial-venous fistula in 1). Conclusion In the majority of very young adults catheter ablation for AF is effective, and associated with an acceptable complication rate. SHD and obesity are predictors for AF recurrence in this population.