Miracle-dz/UniFAR-FTUs huggingface dataset:
Nerve activity recordings in routine human intestinal biopsies

Background Most direct understanding of enteric nerve (patho)physiology has been obtained by electrode and imaging techniques in animal models and human surgical samples. Until now, neuronal activity recordings from a more accessible human tissue source have remained a true challenge. Objectives To record nerve activity in human intestinal biopsies using imaging techniques. Design Submucous plexus was isolated from duodenal biopsies. Enteric nerves were functionally and morphologically examined using calcium (Ca2+) imaging and immunohistochemistry. Exogenous application of high-K+ solution, the nicotinic cholinergic receptor agonist (1,1-dimethyl-4-phenylpiperazinium; DMPP) or serotonin (5-HT), and electrical stimulation of interganglionic fibre tracts were used to activate the neurons, and intracellular Ca2+ concentrations ([Ca2+]i) were monitored. Enteric ganglia were stained with neuronal and glial markers. Results Using high-K+ solution, 146 neurons were identified in 70 ganglia (44 biopsies from 29 subjects). The exogenous application of DMPP or 5-HT caused a transient [Ca2+]i increase, respectively, in 68% and 63% of the neurons identified by high-K+. Electrical stimulation evoked responses in 57% of the neurons; these responses were totally or partly suppressed by tetrodotoxin or zero-Ca2+ solution, respectively. Immunohistochemical analysis showed both isolated neurons and ganglia interconnected by typical interganglionic fibre bundles. The average number of ganglia was 7.7±6.0 per biopsy and each ganglion contained on average 4.5±1.2 neurons. Conclusion In this study, for the first time, live recordings were performed of nerve activity in intestinal biopsies. This novel approach is of key importance to study living neurons in both health and disease and to test newly developed compounds in an in-vitro human tissue model.
Chemogenetic stimulation of striatal projection neurons modulates responses to Parkinson’s disease therapy

Parkinson’s disease (PD) patients experience loss of normal motor function (hypokinesia), but can develop uncontrollable movements known as dyskinesia upon treatment with L-DOPA. Poverty or excess of movement in PD has been attributed to overactivity of striatal projection neurons forming either the indirect (iSPNs) or the direct (dSPNs) pathway, respectively. Here, we investigated the two pathways’ contribution to different motor features using SPN type–specific chemogenetic stimulation in rodent models of PD (PD mice) and L-DOPA–induced dyskinesia (LID mice). Using the activatory Gq-coupled human M3 muscarinic receptor (hM3Dq), we found that chemogenetic stimulation of dSPNs mimicked, while stimulation of iSPNs abolished the therapeutic action of L-DOPA in PD mice. In LID mice, hM3Dq stimulation of dSPNs exacerbated dyskinetic responses to L-DOPA, while stimulation of iSPNs inhibited these responses. In the absence of L-DOPA, only chemogenetic stimulation of dSPNs mediated through the Gs-coupled modified rat muscarinic M3 receptor (rM3Ds) induced appreciable dyskinesia in PD mice. Combining D2 receptor agonist treatment with rM3Ds-dSPN stimulation reproduced all symptoms of LID. These results demonstrate that dSPNs and iSPNs oppositely modulate both therapeutic and dyskinetic responses to dopamine replacement therapy in PD. We also show that chemogenetic stimulation of different signaling pathways in dSPNs leads to markedly different motor outcomes. Our findings have important implications for the design of effective antiparkinsonian and antidyskinetic drug therapies.
ONLINE SHOPPING ACCEPTANCE MODEL — A CRITICAL SURVEY OF CONSUMER FACTORS IN ONLINE SHOPPING

Since the late 1990s, online shopping has taken off as an increasing number of consumers purchase increasingly diversified products on the Internet. Given that how to attract and retain consumers is critical to the success of online retailers, research on the antecedents of consumer acceptance of online shopping has attracted widespread attention. There has yet to be a holistic view of online shopping acceptance from the perspective of consumers. In this research, we conducted an extensive survey of extant related studies and synthesized their findings into a reference model called OSAM (Online Shopping Acceptance Model) to explain consumer acceptance of online shopping. Our literature survey reveals that a myriad of factors have been examined in the context of online shopping and mixed results on those factors have been reported. The proposed model helps reconcile conflicting findings, discover recent trends in this line of research, and shed light on future research directions.
The Effects of Methylphenidate on Resting-State Functional Connectivity of the Basal Nucleus of Meynert, Locus Coeruleus, and Ventral Tegmental Area in Healthy Adults

Background: Methylphenidate (MPH) influences catecholaminergic signaling. Extant work examined the effects of MPH on the neural circuits of attention and cognitive control, but few studies have investigated the effect of MPH on the brain's resting-state functional connectivity (rsFC). Methods: In this observational study, we compared rsFC of a group of 24 healthy adults who were administered an oral 45 mg dose of MPH with a group of 24 age and gender matched controls who did not receive MPH. We focused on three seed regions: basal nucleus of Meynert (BNM), locus coeruleus (LC), and ventral tegmental area/substantia nigra, pars compacta (VTA/SNc), each providing cholinergic, noradrenergic and dopaminergic inputs to the cerebral cortex. Images were pre-processed and analyzed as in our recent work (Li et al., 2014; Zhang et al., 2015). We used one-sample t-test to characterize group-specific rsFC of each seed region and two-sample t-test to compare rsFC between groups. Results: MPH reversed negative connectivity between BNM and precentral gyri. MPH reduced positive connectivity between LC and cerebellum, and induced positive connectivity between LC and right hippocampus. MPH decreased positive VTA/SNc connectivity to the cerebellum and putamen, and reduced negative connectivity to left middle occipital gyrus. Conclusion: MPH had distinct effects on the rsFC of BNM, LC, and VTA/SNc in healthy adults. These new findings may further our understanding of the role of catecholaminergic signaling in Attention Deficit Hyperactivity Disorder (ADHD) and Parkinson's disease and provide insights into the therapeutic mechanisms of MPH in the treatment of clinical conditions that implicate catecholaminergic dysfunction.
Acetylcholine negatively regulates development of the neuromuscular junction through distinct cellular mechanisms

Emerging evidence suggests that the neurotransmitter acetylcholine (ACh) negatively regulates the development of the neuromuscular junction, but it is not clear if ACh exerts its effects exclusively through muscle ACh receptors (AChRs). Here, we used genetic methods to remove AChRs selectively from muscle. Similar to the effects of blocking ACh biosynthesis, eliminating postsynaptic AChRs increased motor axon branching and expanded innervation territory, suggesting that ACh negatively regulates synaptic growth through postsynaptic AChRs. However, in contrast to the effects of blocking ACh biosynthesis, eliminating postsynaptic AChRs in agrin-deficient mice failed to restore deficits in pre- and postsynaptic differentiation, suggesting that ACh negatively regulates synaptic differentiation through nonpostsynaptic receptors. Consistent with this idea, the ACh agonist carbachol inhibited presynaptic specialization of motorneurons in vitro. Together, these data suggest that ACh negatively regulates axon growth and presynaptic specialization at the neuromuscular junction through distinct cellular mechanisms.
Mip protein of Legionella pneumophila exhibits peptidyl‐prolyl‐cis/trans isomerase (PPIase) activity

Legionella pneumophila is an intracellular parasite which is able to survive and multiply in human monocytes and alveolar macrophages. The Mip (macro‐phage infectivity potentiator) protein has been shown to be an essential virulence factor. A search of translated nucleic acid data bases has shown that the Mip protein from strain Wadsworth possesses regions homologous to those found in the FK506‐binding proteins (FKBPs) of several different eukaryotic organisms. FKBPs are able to bind to the immunosuppressant macrolide FK506 and possess peptidyl‐prolyl cis/trans isomerase (PPIase) activity. The gene coding for the Mip protein was cloned from the chromosome of L. pneumophila strain Philadelphia I and sequenced. It was synthesized in Escherichia coli K‐12 and after purification it exhibited PPIase activity catalysing the slow cis/trans isomerization of prolyl peptide bonds in oligopeptides. Mip is inhibited by FK506 and fully resistant to cyclosporin A, as was also found for the recently characterized FKBP‐type PPlases of eukaryotes. However, the N‐terminal extension of Mip and/or the substitutions of the variable amino acids in the C‐terminal FKBP core lead to variations, when compared with eukaryotic FKBPs, in substrate specificity with the oligopeptide substrates of type Suc‐Ala‐Xaa‐Pro‐Phe‐4‐nitroanilide. Nevertheless, the Legionella Mip factor represents a bacterial gene product which shares some characteristics normally found in eukaryotic proteins. In view of the activity of PPIases in protein‐folding reactions, such prokaryotic FKBP analogues may represent a new class of bacterial pathogenicity factors.
The Effect of Two Different Hand Exercises on Grip Strength, Forearm Circumference, and Vascular Maturation in Patients Who Underwent Arteriovenous Fistula Surgery

Objective To compare the effect of two different hand exercises on hand strength and vascular maturation in patients who underwent arteriovenous fistula surgery. Methods We recruited 18 patients who had chronic kidney disease and had undergone arteriovenous fistula surgery for hemodialysis. After the surgery, 10 subjects performed hand-squeezing exercise with GD Grip, and other 8 subjects used Soft Ball. The subjects continued the exercises for 4 weeks. The hand grip strength, pinch strength (tip, palmar and lateral pinch), and forearm circumference of the subjects were assessed before and after the hand-squeezing exercise. The cephalic vein size, blood flow velocity and volume were also measured by ultrasonography in the operated limb. Results All of the 3 types of pinch strengths, grip strength, and forearm circumference were significantly increased in the group using GD Grip. Cephalic vein size and blood flow volume were also significantly increased. However, blood flow velocity showed no difference after the exercise. The group using Soft Ball showed a significant increase in the tip and lateral pinch strength and forearm circumference. The cephalic vein size and blood flow volume were also significantly increased. On comparing the effect of the two different hand exercises, hand-squeezing exercise with GD Grip had a significantly better effect on the tip and palmar pinch strength than hand-squeezing exercise with Soft Ball. The effect on cephalic vein size was not significantly different between the two groups. Conclusion The results showed that hand squeezing exercise with GD Grip was more effective in increasing the tip and palmar pinch strength compared to hand squeezing exercise with soft ball.
Psychological disturbance in graves ophthalmopathy.

OBJECTIVE To study mood disturbance in Graves ophthalmopathy. METHODS Forty-eight patients (mean age, 55 years; 40 women and 8 men) with Graves ophthalmopathy from a university-based referral center were classified into two groups, 24 with moderate/severe disease (study group) and 24 with negligible/mild disease (control group). The groups were matched with regard to demographic and medical characteristics. All participants completed a mood survey to assess differences in degree of emotional distress. MAIN OUTCOME MEASURE The Profile of Mood States survey, a 65-item self-reported inventory designed to assess emotional distress, was the primary outcome measure. A total mood disturbance score was assigned by summing the scores derived on the 6 subscales of the survey--tension, depression, vigor, confusion, fatigue, and anger. RESULTS Analysis of variance revealed that patients with moderate/severe Graves ophthalmopathy showed significantly greater emotional distress than patients with mild/negligible Graves ophthalmopathy on the Profile of Mood States mean total score (P<.001). Additionally, patients who had disfigurement (proptosis) as the predominant clinical feature had significantly elevated emotional distress compared with the control group (P = .01), whereas no significant difference was detected between the control group and patients with diplopia as the predominant clinical feature (P = .20). CONCLUSION Patients with moderate to severe Graves ophthalmopathy have significant mood disturbance, especially when disfiguring signs are predominant. We propose that evaluation of the psychological burden of the disease should be considered in routine follow-up and in decisions regarding treatment.
Can telomere shortening explain sigmoidal growth curves?

A general branching process model is proposed to describe the shortening of telomeres in eukaryotic chromosomes. The model is flexible and incorporates many special cases to be found in the literature. In particular, we show how telomere shortening can give rise to sigmoidal growth curves, an idea first expressed by Portugal et al. [A computational model for telomere-dependent cell-replicative aging, BioSystems 91 (2008), pp. 262–267]. We also demonstrate how other types of growth curves arise if telomere shortening is mitigated by other cellular processes. We compare our results with published data sets from the biological literature.
Characterization of autonomic receptors in the smooth musculature of human Graafian follicle.

Various types of autonomic receptors were studied in isolated, 2 X 10 mm-size strips from the protruding part of human Graafian follicles obtained shortly before ovulation. The strip was mounted in an organ bath for recording of mechanical activity in the presence of different agonists and specific antagonists. The potency rank for sympathomimetics in their contractile effect (norepinephrine > epinephrine > penylephrine > isoproterenol) and the inhibition produced by phenoxybenzamine and piperoxan suggested the presence of a-receptors. The dissociation constant for their complex with norepinephrine (KA) was 1.68 X 10’M, and with piperoxan (KB) 7.90 X
Inhalation of Fine Particulate Matter Impairs Endothelial Progenitor Cell Function Via Pulmonary Oxidative Stress

Objective— Exposure to fine particulate matter (PM2.5) air pollution is associated with the depletion of circulating endothelial progenitor cells (EPCs), as well as vascular injury and dysfunction. Nevertheless, it remains unclear whether PM2.5 exposure leads to significant impairments in EPC function. Hence, we studied the effects of PM2.5 on EPC-mediated recovery of vascular perfusion after hindlimb ischemia and examined the mechanisms whereby PM2.5 exposure affects EPC abundance and function. Approach and Results— In comparison with EPCs isolated from mice breathing filtered air, EPCs from mice exposed for 9 consecutive days (6 hours per day) to concentrated ambient PM2.5 (CAP) had defects in both proliferation and tube formation. However, CAP exposure of mice overexpressing extracellular superoxide dismutase (ecSOD-Tg) in the lungs did not affect EPC tube formation. Exposure to CAP also suppressed circulating EPC levels, VEGF (vascular endothelial growth factor)-stimulated aortic Akt phosphorylation, and plasma NO levels in wild-type but not in ecSOD-Tg mice. EPCs from CAP-exposed wild-type mice failed to augment basal recovery of hindlimb perfusion when injected into unexposed mice subjected to hindlimb ischemia; however, these deficits in recovery of hindlimb perfusion were absent when using EPCs derived from CAP-exposed ecSOD-Tg mice. The improved reparative function of EPCs from CAP-exposed ecSOD-Tg mice was also reflected by greater expression of Mmp-9 and Nos3 when compared with EPCs from CAP-exposed wild-type mice. Conclusions— Exposure to PM2.5 impairs EPC abundance and function and prevents EPC-mediated vascular recovery after hindlimb ischemia. This defect is attributed, in part, to pulmonary oxidative stress and was associated with vascular VEGF resistance and a decrement in NO bioavailability.
Reading Between the Minds

An ideal empathizer may attend to another person’s behavior in order to understand that person, but it is also possible that accurately understanding other people involves top-down strategies. We hypothesized that perceivers draw on stereotypes to infer other people’s thoughts and that stereotype use increases perceivers’ accuracy. In this study, perceivers (N = 161) inferred the thoughts of multiple targets. Inferences consistent with stereotypes for the targets’ group (new mothers) more accurately captured targets’ thoughts, particularly when actual thought content was also stereotypic. We also decomposed variance in empathic accuracy into thought, target, and perceiver variance. Although past research has frequently focused on variance between perceivers or targets (which assumes individual differences in the ability to understand other people or be understood, respectively), the current study showed that the most substantial variance was found within targets because of differences among thoughts.
Preparation and Characterization of Micronized Artemisinin via a Rapid Expansion of Supercritical Solutions (RESS) Method

The particle sizes of pharmaceutical substances are important for their bioavailability. Bioavailability can be improved by reducing the particle size of the drug. In this study, artemisinin was micronized by the rapid expansion of supercritical solutions (RESS). The particle size of the unprocessed white needle-like artemisinin particles was 30 to 1200 μm. The optimum micronization conditions are determined as follows: extraction temperature of 62 °C, extraction pressure of 25 MPa, precipitation temperature 45 °C and nozzle diameter of 1000 μm. Under the optimum conditions, micronized artemisinin with a (mean particle size) MPS of 550 nm is obtained. By analysis of variance (ANOVA), extraction temperature and pressure have significant effects on the MPS of the micronized artemisinin. The particle size of micronized artemisinin decreased with increasing extraction temperature and pressure. Moreover, the SEM, LC-MS, FTIR, DSC and XRD allowed the comparison between the crystalline initial state and the micronization particles obtained after the RESS process. The results showed that RESS process has not induced degradation of artemisinin and that processed artemisinin particles have lower crystallinity and melting point. The bulk density of artemisinin was determined before and after RESS process and the obtained results showed that it passes from an initial density of 0.554 to 0.128 g·cm−3 after the processing. The decrease in bulk density of the micronized powder can increase the liquidity of drug particles when they are applied for medicinal preparations. These results suggest micronized powder of artemisinin can be of great potential in drug delivery systems.
Persistence of Anticancer Activity in Berry Extracts after Simulated Gastrointestinal Digestion and Colonic Fermentation

Fruit and vegetable consumption is associated at the population level with a protective effect against colorectal cancer. Phenolic compounds, especially abundant in berries, are of interest due to their putative anticancer activity. After consumption, however, phenolic compounds are subject to digestive conditions within the gastrointestinal tract that alter their structures and potentially their function. However, the majority of phenolic compounds are not efficiently absorbed in the small intestine and a substantial portion pass into the colon. We characterized berry extracts (raspberries, strawberries, blackcurrants) produced by in vitro-simulated upper intestinal tract digestion and subsequent fecal fermentation. These extracts and selected individual colonic metabolites were then evaluated for their putative anticancer activities using in vitro models of colorectal cancer, representing the key stages of initiation, promotion and invasion. Over a physiologically-relevant dose range (0–50 µg/ml gallic acid equivalents), the digested and fermented extracts demonstrated significant anti-genotoxic, anti-mutagenic and anti-invasive activity on colonocytes. This work indicates that phenolic compounds from berries undergo considerable structural modifications during their passage through the gastrointestinal tract but their breakdown products and metabolites retain biological activity and can modulate cellular processes associated with colon cancer.
Sign Language Recognition Using Boosted Volumetric Features

This paper proposes a method for sign language recognition that bypasses the need for tracking by classifying the motion directly. The method uses the natural extension of haar like features into the temporal domain, computed efficiently using an integral volume. These volumetric features are assembled into spatio-temporal classifiers using boosting. Results are presented for a fast feature extraction method and 2 different types of boosting. These configurations have been tested on a data set consisting of both seen and unseen signers performing 5 signs producing competitive results.
Cognitive Behaviour Therapy for Depression and Anxiety in Parkinson’s Disease

Abstract Evidence is reviewed demonstrating that cognitive behavior therapy (CBT) is effective in the treatment of depression and anxiety in Parkinson’s disease. The aims were to review the extant literature, specify a model of cognitive and behavioral maintenance factors in depression and anxiety in Parkinson’s disease and provide a guide to treatment. It is argued that treatment should take into account specific cognitive and behavioral maintaining factors. Symptoms of depression and anxiety are highly prevalent in Parkinson’s disease and therapists should consider how to augment the efficacy of CBT for patients with Parkinson’s disease. Cognitive and behavioral interventions can help people overcome some of the challenges in living with PD by maximizing wellbeing and overall quality of life.
Parkinson's Disease Subtypes Identified from Cluster Analysis of Motor and Non-motor Symptoms

Parkinson's disease is now considered a complex, multi-peptide, central, and peripheral nervous system disorder with considerable clinical heterogeneity. Non-motor symptoms play a key role in the trajectory of Parkinson's disease, from prodromal premotor to end stages. To understand the clinical heterogeneity of Parkinson's disease, this study used cluster analysis to search for subtypes from a large, multi-center, international, and well-characterized cohort of Parkinson's disease patients across all motor stages, using a combination of cardinal motor features (bradykinesia, rigidity, tremor, axial signs) and, for the first time, specific validated rater-based non-motor symptom scales. Two independent international cohort studies were used: (a) the validation study of the Non-Motor Symptoms Scale (n = 411) and (b) baseline data from the global Non-Motor International Longitudinal Study (n = 540). k-means cluster analyses were performed on the non-motor and motor domains (domains clustering) and the 30 individual non-motor symptoms alone (symptoms clustering), and hierarchical agglomerative clustering was performed to group symptoms together. Four clusters are identified from the domains clustering supporting previous studies: mild, non-motor dominant, motor-dominant, and severe. In addition, six new smaller clusters are identified from the symptoms clustering, each characterized by clinically-relevant non-motor symptoms. The clusters identified in this study present statistical confirmation of the increasingly important role of non-motor symptoms (NMS) in Parkinson's disease heterogeneity and take steps toward subtype-specific treatment packages.