Miracle-dz/UniFAR-FTUs huggingface dataset:
Reduction of Immunoreactivity Against the C-Terminal Region of the Intracellular α-Synuclein by Exogenous α-Synuclein Aggregates: Possibility of Conformational Changes.

BACKGROUND The formation of intracellular aggregates containing α-synuclein (α-syn) is a main pathological feature of Parkinson disease. The propagation of α-syn aggregation via cell-to-cell transmission has been implicated in the progression of Parkinson disease. OBJECTIVE Our aim is to clarify the molecular mechanisms underlying the formation of intracellular aggregation by extracellular α-syn. METHODS We investigated the effects of exogenous α-syn aggregates on intracellular α-syn immunoreactivity in α-syn-overexpressing SH-SY5Y cells using two antibodies to distinct epitopes of α-syn. To obtain α-syn aggregates, α-syn solution was aged with continuous agitation. RESULTS Immunoreactivity against the acidic C-terminal domain of the intracellular α-syn was reduced by exposure to agedα-syn, whereas that against the hydrophobic non-amyloid component region was not changed. The reduction in immunoreactivity was not suppressed by protease inhibitors but was mimicked by neutralization of the negative charges on the C-terminal of the intracellular α-syn induced by spermine or extracellular acidification. CONCLUSIONS These results suggest that the reduction in immunoreactivity is attributed not to proteolytic cleavage but to a conformational change at the C-terminus of the intracellular α-syn. The conformational change at the C-terminus of the intracellular α-syn might be involved in an initial step of fibril formation by exogenous α-syn aggregates.
Progenitor Cells and Clinical Outcomes in Patients With Heart Failure

Background Endogenous regenerative capacity, assessed as circulating progenitor cell (PC) numbers, is an independent predictor of adverse outcomes in patients with cardiovascular disease. However, their predictive role in heart failure (HF) remains controversial. We assessed the relationship between the number of circulating PCs and the pathogenesis and severity of HF and their impact on incident HF events. Methods and Results We recruited 2049 adults of which 651 had HF diagnosis. PCs were enumerated by flow cytometry as CD45med+ blood mononuclear cells expressing CD34, CD133, vascular endothelial growth factor receptor-2, and chemokine (C-X-C motif) receptor 4 epitopes. PC subsets were lower in number in HF and after adjustment for clinical characteristics in multivariable analyses, a low CD34+ and CD34+/CXCR+ cell count remained independently associated with a diagnosis of HF (P<0.01). PC levels were not significantly different in reduced versus preserved ejection fraction patients. In 514 subjects with HF, there were 98 (19.1%) all-cause deaths during a 2.2±1.5-year follow-up. In a Cox regression model adjusting for clinical variables, hematopoietic-enriched PCs (CD34+, CD34+/CD133+, and CD34+/CXCR4+) were independent predictors of all-cause death (hazard ratio 2.0, 1.6, 1.6-fold higher mortality, respectively; P<0.03) among HF patients. Endothelial-enriched PCs (CD34+/VEGF+) were independent predictors of mortality in patients with HF with preserved ejection fraction only (hazard ratio, 5.0; P=0.001). Conclusions PC levels are lower in patients with HF, and lower PC counts are strongly and independently predictive of mortality. Strategies to increase PCs and exogenous stem cell therapies designed to improve regenerative capacity in HF, especially, in HF with preserved ejection fraction, need to be further explored.
Mechanical design and control of inflatable robotic arms for high positioning accuracy

Abstract In recent years, inflatable robotic arms have been developed so that physical contact with humans and working environments could be performed safety. In industry, there is a growing demand for safe industrial robots to collaborate with people and work in various environments. In general, however, the positioning accuracy of inflatable robotic arms has not been discussed. This paper proposes an inflatable link structure and a non-inflatable joint structure that could realize a high positioning accuracy for such robotic arms. This paper experimentally demonstrates that these structures can improve positioning accuracy. In addition to these structures, the joint torque characteristics of the inflatable robotic arms were investigated. In order to perform accurate motion control, a visual feedback control method was introduced for inflatable robotic arms. The mechanism and control system used in this paper can improve the positioning accuracy performance of inflatable robots. A 2-DOF inflatable robotic arm and a camera system were found to be able to achieve a high positioning accuracy (i.e. less than 1 mm).
Photodynamic therapy with topical application of 5-aminolevulinic acid in the treatment of actinic keratoses: an initial clinical study.

BACKGROUND The incidence of actinic keratoses (AK) is rising and there is still a need for therapeutic alternatives. OBJECTIVE To demonstrate the efficacy and tolerability of topical photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) in the treatment of AK. METHODS Ten patients with 36 lesions (19 at hands and arms, 17 on the head) received ALA-PDT once (occlusive application of a 10% ALA emulsion for 6 h, irradiation with red light, 580-740 nm, 150 J/cm2) and were then monitored for 3 months. Therapeutic efficacy was judged using a score evaluating infiltration and keratosis of AK. RESULTS After 28 days, significantly lower score sums were observed (head: mean = 15%; hand: mean = 67%) compared to the initial score (100%). Complete remission was achieved in 71% of AK localized on the head. No notable side effects were observed. CONCLUSION This study demonstrated the potential of good efficacy and tolerability in the treatment of AK using topical ALA-PDT. How efficacy for lesions on the hand can be improved and whether PDT is able to concur with established treatment modalities remains to be shown in further studies.
The Association of HLA-class I Genes and the Extent of Atherosclerotic Plaques in Patients with Psoriatic Disease

Objective. To investigate the association between HLA susceptibility and disease severity markers and the extent of atherosclerosis in patients with psoriatic disease. Methods. White patients with psoriatic arthritis (PsA) and psoriasis without PsA (PsC) were recruited. An ultrasound of the carotid arteries was performed and the size of each atherosclerotic plaque was measured. The resulting score, the total plaque area (TPA), represented the extent of atherosclerosis. HLA genotyping was performed using sequence-specific oligonucleotide probes. The association between 10 HLA susceptibility and severity markers of PsC and PsA and the severity of atherosclerosis was assessed by ordinal logistic regression models adjusted for age, sex, and cardiovascular (CV) risk factors. Results. The study involved 411 patients (273 PsA, 138 PsC). Of them, 61.8% had at least 1 atherosclerotic plaque. HLA-B*13:02 and HLA-C*06:02 were associated with more severe atherosclerosis (age- and sex-adjusted OR 2.31, 95% CI 1.23–4.32 and OR 1.68, 95% CI 1.12–2.52, respectively). HLA-B*38:01 was associated with less severe atherosclerosis (OR 0.49, 95% CI 0.28–0.86). These associations remained statistically significant after adjusting for CV risk factors. Higher levels of erythrocyte sedimentation rate (ESR) were associated with more severe atherosclerosis (age- and sex-adjusted OR 1.33, p = 0.02). HLA-B*13:02–positive (p = 0.01) as well as HLA-C*06:02–positive (p = 0.008) patients had higher levels of ESR over time. Conclusion. HLA-C*06:02 and B*13:02 alleles are associated with a higher burden of atherosclerosis in patients with psoriatic disease. This association may be mediated by a higher level of systemic inflammation.
Results of a European Comparative Randomized Study Comparing Oral Bropirimine versus Intravesical BCG Treatment in BCG-Naive Patients with Carcinoma in situ of the Urinary Bladder

Objectives: This European phase III clinical trial was part of an intercontinental study which was closed prematurely by the sponsor. The study was designed to compare the effects of oral bropirimine with intravesical BCG, the current standard treatment in patients with newly diagnosed bladder carcinoma in situ (CIS). Methods: A total of 55 BCG-naive patients with bladder CIS were randomized to receive bropirimine (n = 27) or BCG (n = 28). Bropirimine was orally administered at a dose of 3 g/day for 3 consecutive days with a 4-day drug-free interval for up to 1 year. BCG-Tice instillations were administered weekly for 2 × 6 weeks. Both biopsies and cytology had to be negative for the patient to be considered a complete responder (CR). Results: The percentage of dropouts for all of the adverse events was 4% for bropirimine and 14% for BCG. The most frequently reported local events in the bropirimine- versus the BCG-treated group were irritative complaints, 64 vs. 89% (p = 0.03) and hematuria, 24 vs. 61% (p < 0.01). The most frequently reported systemic events in the bropirimine- versus the BCG-treated group were fever 4 vs. 21%, flu syndrome 24 vs. 7%, headache 28 vs. 11% and nausea 24 vs. 11% (all p > 0.05). A total of 92% of the patients treated with bropirimine had a CR with a mean duration of 12.6 months (95% CI 9.2–15.9). In the BCG group, all of the patients had a CR with a mean of 12.3 months (95% CI 8.5–16.0). Conclusions: This study shows that bropirimine, an orally administered drug that can be self-administered to outpatients with more acceptable local toxicity compared to BCG, could be an effective first-line therapy in patients with CIS of the urinary bladder. Continued investigation of bropirimine is warranted to increase its clinical utility.
Epizoochorous dispersal by ungulates depends on fur, grooming and social interactions

Abstract The transport phase of the animal‐mediated plant dispersal process is critical to dispersal effectiveness as it determines the spatial distribution of the diaspores released and their chance for further recruitment. Assessing this specific phase of the dispersal process generally requires combining diaspore retention times with the associated distances covered. Here, we specifically tested the effect of grooming behavior, interindividual contacts and ungulate fur on diaspore retention times and associated dispersal distances for the hooked diaspores of Xanthium strumarium L. experimentally attached to tamed individuals of three ungulate species. We used a comparative approach based on differing fur quality on different body zones of these three ungulates. During 6‐hr sessions, we monitored for grooming and social interactions that may induce intended or inadvertent diaspore detachment. Additionally, we proposed innovative approaches to directly assessing diaspore dispersal distances by red deer in situ. Fat‐tailed functions fitted diaspore retention time, highlighting the potential for long‐distance dispersal events. The longer the hair, the higher the retention capacity of diaspores in the animal's fur. As predicted, donkey retained diaspores longer than red deer and dwarf goat; and we also confirmed that diaspores attached to the short hair of the head fell off more quickly than did those on the other body zones. Dwarf goat groomed more often than both red deer and donkey, but also when it carried diaspores. Up to 14% of the diaspores detached from animal fur after specific grooming behavior. We observed, in controlled conditions, for the first time and for each ungulate species, interindividual transfers of diaspores, representing 5% of the diaspores attached to animals’ fur. Our results militate for incorporating animal behavior into plant dispersal modeling approaches.
Intermittent theta-burst transcranial magnetic stimulation for autism spectrum disorder: an open-label pilot study

Objective: Theta-burst stimulation (TBS) modulates synaptic plasticity more efficiently than standard repetitive transcranial magnetic stimulation delivery and may be a promising modality for neuropsychiatric disorders such as autism spectrum disorder (ASD). At present there are few effective interventions for prefrontal cortex dysfunction in ASD. We report on an open-label, pilot study of intermittent TBS (iTBS) to target executive function deficits and restricted, repetitive behaviors in male children and adolescents with ASD. Methods: Ten right-handed, male participants, aged 9-17 years with ASD were enrolled in an open-label trial of iTBS treatment. Fifteen sessions of neuronavigated iTBS at 100% motor threshold targeting the right dorsolateral prefrontal cortex were delivered over 3 weeks. Results: Parent report scores on the Repetitive Behavior Scale Revised and the Yale-Brown Obsessive Compulsive Scale demonstrated improvements with iTBS treatment. Participants demonstrated improvements in perseverative errors on the Wisconsin Card Sorting Test and total time for the Stroop test. The iTBS treatments were well tolerated with no serious adverse effects. Conclusion: These preliminary results suggest that further controlled interventional studies of iTBS for ASD are warranted.
Substrate-Integrated Waveguide Filters Based on Dual-Mode Air-Filled Resonant Cavities

This paper presents the design and implementation of a novel class of substrate-integrated waveguide (SIW) filters, based on partially air-filled cavity resonators. Removing the dielectric in a portion of the SIW cavity allows obtaining dual-mode cavities: such cavities represent a doublet, used as the building blocks in the design of filters. A thorough modal analysis of the air-filled resonant cavity based on transmission lines’ representation and a detailed study of the doublet permit to demonstrate a full control of the operation frequency, pass bandwidth, spurious-free region, and position of the transmission zeros of the filter. This paper presents the design, fabrication, and measurement of several two-pole filters based on this concept, with the aim to show the capabilities of the proposed structure and of the design technique. A five-pole filter is also presented, to describe the extension of the proposed approach to higher order filters.
Effects of Leucocyte Depletion on Rheologic Properties of Human CPDA-1 Blood

Background and Objectives: Leucocyte depletion improves the quality of stored blood units. We have studied its role on blood viscosity. Materials and Methods: Viscosity of CPDA-1 blood units was measured in a Couette viscometer at shear rates of 94.5 and 0.1 s–1 prior to and following filtration with the Leukotrap® A1 system on day 0 and after 21 days at +4°C. Results: On day 0, high but not low shear viscosity was significantly decreased. The red blood cell morphology was unaffected. On day 21, blood viscosity was increased similarly for unfiltered and filtered samples at both shear rates. The echinocytosis observed after storage correlated with the increase in viscosity. Conclusion: Leucocyte depletion is associated with a decrease in high shear viscosity. This effect is, however, completely lost after 21 days.
Incidence of Previously Undiagnosed Atrial Fibrillation Using Insertable Cardiac Monitors in a High-Risk Population: The REVEAL AF Study

Importance In approximately 20% of atrial fibrillation (AF)–related ischemic strokes, stroke is the first clinical manifestation of AF. Strategies are needed to identify and therapeutically address previously undetected AF. Objective To quantify the incidence of AF in patients at high risk for but without previously known AF using an insertable cardiac monitor. Design, Setting, and Participants This prospective, single-arm, multicenter study was conducted from November 2012 to January 2017. Visits took place at 57 centers in the United States and Europe. Patients with a CHADS2 score of 3 or greater (or 2 with at least 1 additional risk factor) were enrolled. Approximately 90% had nonspecific symptoms potentially compatible with AF, such as fatigue, dyspnea, and/or palpitations. Exposures Patients underwent monitoring with an insertable cardiac monitor for 18 to 30 months. Main Outcomes and Measures The primary end point was adjudicated AF lasting 6 or more minutes and was assessed at 18 months. Other analyses included detection rates at points from 30 days to 30 months and among CHADS2 score subgroups. Median time from insertion to detection and the percentage of patients subsequently prescribed oral anticoagulation therapy was also determined. Results A total of 446 patients were enrolled; 233 (52.2%) were male, and the mean (SD) age was 71.5 (9.9) years. A total of 385 patients (86.3%) received an insertable cardiac monitor, met the primary analysis cohort definition, and were observed for a mean (SD) period of 22.5 (7.7) months. The detection rate of AF lasting 6 or more minutes at 18 months was 29.3%. Detection rates at 30 days and 6, 12, 24, and 30 months were 6.2%, 20.4%, 27.1%, 33.6%, and 40.0%, respectively. At 18 months, AF incidence was similar among patients with CHADS2 scores of 2 (24.7%; 95% CI, 17.3-31.4), 3 (32.7%; 95% CI, 23.8-40.7), and 4 or greater (31.7%; 95% CI, 22.0-40.3) (P = .23). Median (interquartile) time from device insertion to first AF episode detection was 123 (41-330) days. Of patients meeting the primary end point, 13 (10.2%) had 1 or more episodes lasting 24 hours or longer, and oral anticoagulation therapy was prescribed for 72 patients (56.3%). Conclusions and Relevance The incidence of previously undiagnosed AF may be substantial in patients with risk factors for AF and stroke. Atrial fibrillation would have gone undetected in most patients had monitoring been limited to 30 days. Further trials regarding the value of detecting subclinical AF and of prophylactic therapies are warranted. Trial Registration clinicaltrials.gov Identifier: NCT01727297
Application of microscope‐based scanning software (Panoptiq) for the interpretation of cervicovaginal cytology specimens

Digital pathology increasingly has been gaining the attention of pathologists worldwide. However, the application of digital cytology by Panoptiq (ViewsIQ, Vancouver, Canada) microscope‐based scanning software is relatively unexplored. Panoptiq enables the operator to combine low‐power panoramic digital images with z‐stacks at regions of interest with a significantly smaller image size than that obtained by whole‐slide scanning. The current study aimed to evaluate the feasibility of the use of Panoptiq in the digital interpretation of cervicovaginal cytology specimens in comparison with conventional light microscopy.
Sevoflurane sparing effect of dexmedetomidine in patients undergoing laparoscopic cholecystectomy: A randomized controlled trial

Background and Aims: Sevoflurane is an excellent but expensive anesthetic agent for laparoscopic cholecystectomy. To decrease sevoflurane consumption during surgery adjuvants like dexmedetomidine may be used. Dexmedetomidine is a recently introduced drug which alleviates the stress response of surgery, produces sedation and analgesia. We aimed to evaluate sevoflurane sparing effect of dexmedetomidine in patients undergoing laparoscopic cholecystectomy under entropy-guided general anesthesia (GA). Material and Methods: In this prospective randomized control study, 100 American Society of Anesthesiologists physical status I–II adult surgical patients scheduled to undergo laparoscopic cholecystectomy were enrolled. Patients were randomly divided into two groups (n = 50). In dexmedetomidine group, patients received intravenous (IV) dexmedetomidine 0.5 μg/kg over 10 min before induction followed by 0.5 μg/kg/h infusion while in control group, patients received the same volume of normal saline. Results: Sevoflurane consumption was 41% lower in dexmedetomidine group as compared to control group (7.1 [1.6] vs. 12.1 [1.9] ml, P <0.001). A 40% reduction was observed in induction dose of propofol (83.0 [19.1] vs. 127.6 [24.8] mg, P <0.001). Mean Riker sedation-agitation score, visual analog score for pain and Aldrete's score were significantly lower in dexmedetomidine group as compared to control group. None of the patients experienced any significant side effects. Conclusion: A 41% reduction in sevoflurane consumption was observed in patients receiving IV dexmedetomidine as an adjuvant in patients undergoing laparoscopic cholecystectomy under GA.
Evolution of Solar Subsurface Meridional Flows in the Declining Phase of Cycle 23

We study the evolution of meridional flows in the solar convection zone extending to a depth of 0.793 R☉ in the period 2000-2003 with helioseismic data taken with the Taiwan Oscillation Network (TON) using the technique of time-distance helioseismology. The meridional flows of each hemisphere formed a single-cell pattern in the convection zone at the solar minimum. An additional divergent flow was created at active latitudes in both hemispheres as the activity developed. The amplitude of this divergent flow correlates with the sunspot number: it increased from solar minimum to maximum (from 1996 to 2000), and then decreased from 2000 to 2003 with the sunspot number. The amplitude of the divergent flow increases with depth from 0.987 R☉ to a depth of about 0.9 R☉, and then decreases with depth at least down to 0.793 R☉.
Low recurrence rate of high-grade cervical intraepithelial neoplasia after successful excision and routine colposcopy during follow-up

Abstract The aim of the present cohort study was to assess the long-term (follow-up period up to 22 years) recurrence rate of preinvasive disease and the newly detected invasive disease rate in a cohort of women treated with excisional methods for high-grade cervical intraepithelial neoplasia (CIN). Women treated with large loop excision of the transformation zone (LLETZ) and cold knife conization (CKC) for histologically proven high-grade CIN were followed up for up to 22 years. Surgical specimens underwent histological examination and the status of endocervical as well as ectocervical margins was recorded. Follow-up protocol included conventional Pap test, colposcopy and pelvic examination at 3, 6, and 12 months after the initial treatment, and every 12 months thereafter, provided that the results were normal. In case of high-grade cytological findings and/or atypical colposcopic impression, multiple punch biopsies were taken in order to verify or exclude recurrent disease. In total, 804 women were followed for a mean time of 77.1 months (range: 6–266). LLETZ was used in 569 (70.7%) and CKC in 235 cases (29.2%). No woman developed invasive cervical cancer. Recurrent high-grade disease, developed in 9 women (1.1%, 95% confidence interval 0.5–2.2). Median treatment-to-recurrence time was 46.5 months (range: 6–235.3). One woman treated for squamous CIN2 on clear margins developed adenocarcinoma in situ 59.2 months post-treatment. Women having undergone excisional treatment for high-grade CIN indicate a very low risk for recurrent disease and potentially negligible risk for invasive cancer, provided that a strict and vigorous follow-up is offered after treatment.