Miracle-dz/UniFAR-FTUs huggingface dataset:
Changes in Synaptic Proteins Precede Neurodegeneration Markers in Preclinical Alzheimer's Disease Cerebrospinal Fluid*

In the search for biomarkers of synapse loss associated with Alzheimer's disease (AD), we used shotgun proteomics to identify a panel of 9 synaptic proteins detectable in human cerebrospinal fluid (CSF). Expression at the human synapse was verified using super resolution microscopy. Using SRM, we monitored the panel in CSF from 3 independent clinical cohorts. We report 6 synaptic biomarkers that demonstrate changes in preclinical AD prior to markers of neurodegeneration, which could have clinical value for assessing disease progression. Graphical Abstract Highlights Proteomic analysis of cerebrospinal fluid and identification of synaptic component. Use of super resolution microscopy to verify synapse-specificity in human tissue. Selective reaction monitoring MS (SRM) of synaptic panel in 3 cohorts of Alzheimer's disease cerebrospinal fluid. Synaptic protein changes precede tau in preclinical Alzheimer's disease. A biomarker of synapse loss, an early event in Alzheimer's disease (AD) pathophysiology that precedes neuronal death and symptom onset, would be a much-needed prognostic biomarker. With direct access to the brain interstitial fluid, the cerebrospinal fluid (CSF) is a potential source of synapse-derived proteins. In this study, we aimed to identify and validate novel CSF biomarkers of synapse loss in AD. Discovery: Combining shotgun proteomics of the CSF with an exhaustive search of the literature and public databases, we identified 251 synaptic proteins, from which we selected 22 for further study. Verification: Twelve proteins were discarded because of poor detection by Selected Reaction Monitoring (SRM). We confirmed the specific expression of 9 of the remaining proteins (Calsyntenin-1, GluR2, GluR4, Neurexin-2A, Neurexin-3A, Neuroligin-2, Syntaxin-1B, Thy-1, Vamp-2) at the human synapse using Array Tomography microscopy and biochemical fractionation methods. Exploration: Using SRM, we monitored these 9 synaptic proteins (20 peptides) in a cohort of CSF from cognitively normal controls and subjects in the pre-clinical and clinical AD stages (n = 80). Compared with controls, peptides from 8 proteins were elevated 1.3 to 1.6-fold (p < 0.04) in prodromal AD patients. Validation: Elevated levels of a GluR4 peptide at the prodromal stage were replicated (1.3-fold, p = 0.04) in an independent cohort (n = 60). Moreover, 7 proteins were reduced at preclinical stage 1 (0.6 to 0.8-fold, p < 0.04), a finding that was replicated (0.7 to 0.8-fold, p < 0.05) for 6 proteins in a third cohort (n = 38). In a cross-cohort meta-analysis, 6 synaptic proteins (Calsyntenin-1, GluR4, Neurexin-2A, Neurexin-3A, Syntaxin-1B and Thy-1) were reduced 0.8-fold (p < 0.05) in preclinical AD, changes that precede clinical symptoms and CSF markers of neurodegeneration. Therefore, these proteins could have clinical value for assessing disease progression, especially in preclinical stages of AD.
Bardet‐Biedl syndrome: Antenatal presentation of forty‐five fetuses with biallelic pathogenic variants in known Bardet‐Biedl syndrome genes

Bardet‐Biedl syndrome (BBS) is an emblematic ciliopathy associated with retinal dystrophy, obesity, postaxial polydactyly, learning disabilities, hypogonadism and renal dysfunction. Before birth, enlarged/cystic kidneys as well as polydactyly are the hallmark signs of BBS to consider in absence of familial history. However, these findings are not specific to BBS, raising the problem of differential diagnoses and prognosis. Molecular diagnosis during pregnancies remains a timely challenge for this heterogeneous disease (22 known genes). We report here the largest cohort of BBS fetuses to better characterize the antenatal presentation. Prenatal ultrasound (US) and/or autopsy data from 74 fetuses with putative BBS diagnosis were collected out of which molecular diagnosis was established in 51 cases, mainly in BBS genes (45 cases) following the classical gene distribution, but also in other ciliopathy genes (6 cases). Based on this, an updated diagnostic decision tree is proposed. No genotype/phenotype correlation could be established but postaxial polydactyly (82%) and renal cysts (78%) were the most prevalent symptoms. However, autopsy revealed polydactyly that was missed by prenatal US in 55% of the cases. Polydactyly must be carefully looked for in pregnancies with apparently isolated renal anomalies in fetuses.
Prevalence of nonmedical use and routes of administration for prescription stimulant medications among adults in a substance abuse treatment population

Abstract The aim was to examine prevalence of past 30-day prescription stimulant nonmedical use (NMU) by adults assessed for substance use problems and to better understand patterns of route of administration (ROA) and drug problem severity. Data were collected from a computer administered assessment of substance use problems completed by adults (age ≥ 18) using the Addiction Severity Index-Multimedia Version (ASI-MV®) as part of the clinical intake process between January 2013 and March 2016. A cross-sectional observational study examined prevalence and prescription-adjusted prevalence of past 30-day NMU of prescription stimulants and compound-specific use by ROA (oral, snort, smoke, inject, other oral, and alternate ROA). Compounds of interest were amphetamine extended-release (ER), amphetamine immediate-release (IR), amphetamine mixed salts, methylphenidate ER, and methylphenidate IR. Of 198,411 respondents, 4,185 reported prescription stimulant NMU, prevalence ranged from 0.33% for methylphenidate IR to 1.61% for amphetamine mixed salts. Prescription-adjusted prevalence of NMU was highest for methylphenidate IR (0.51%) and lowest for amphetamine ER (0.28%). The most common ROA was oral, swallowed whole followed by snorting. There was a greater probability of nonmedical prescription stimulant use among respondents with higher drug severity ratings. Results suggest that one should not overlook the impact of prescription stimulant NMU in adults in treatment for substance use problems. NMU of prescription stimulants was associated with riskier routes of administration than reported for college student samples. A pattern of high-risk alternate ROA and increasing drug problem severity has important implications of substance use evaluation.
Acceptance and treatment effects of an internet-delivered cognitive-behavioral intervention for family caregivers of people with dementia: A randomized-controlled trial.

OBJECTIVES The study evaluated the efficacy of an internet-delivered cognitive-behavioral intervention for caregivers of people with dementia and examined acceptance of program characteristics. METHOD Thirty-nine caregivers (M age = 62.11 ± 9.67, 78.4% female) were enrolled in a 2 × 3 randomized-controlled trial (RCT) that compared an intervention and wait-list control group. A cognitive-behavioral intervention program was adapted for delivery via an internet platform. Participants exchanged eight weekly messages with a therapist. RESULTS Treatment satisfaction and acceptance of the program were high. Well-being increased over the intervention duration and intervention group participants were better able to cope with the anticipated death of the care recipient and utilized more psychosocial resources after the intervention ended. Effects were not maintained until follow-up and there were no treatment effects for depression and burden of care. CONCLUSIONS Internet-delivered cognitive-behavioral interventions are suitable for caregivers. A larger RCT needs to investigate possible combinations of classic and internet-delivered programs and confirm efficacy.
Rate limiting factors for DNA transduction induced by weak electromagnetic field

ABSTRACT DNA transduction across aqueous solutions has been reported previously. In this study, we examined a few key factors affecting DNA transduction rate in an extremely low frequency electromagnetic field. These include: the chemical composition of the aqueous solutions, the type of experimental vessel, the dilution step, and the origin of the DNA fragments. The results indicate that partially introducing essential ingredients for DNA amplification (i.e. dNTPs and PCR buffer) to the aqueous solution enhanced the transduction rate greatly, and transduction vessels made of hydrophilic quartz yielded more favorable results than vessels made of hydrophobic plastic. In addition, performing a serial dilution to the transduction solution more than doubled the transduction rate compared to that without the dilution step. For the DNA fragments used in this study, there was one with a pathogenic origin and two with non-pathogenic origins. However, all three fragments achieved DNA transduction regardless of the difference in their origins. The experimental setup for eliminating the false positives caused by both biological and potentially physical contamination is also described.
Henoch-Schonlein purpura in pregnancy: A case report

Henoch-Schonlein purpura is a relatively common pediatric vasculitis. Very few cases of Henoch-Schonlein purpura during pregnancy have been described. Henoch-Schonlein purpura is variable in its presentation, from completely benign to possibly catastrophic complications. This rarely encountered condition in adults can also be a recurrence of a previous childhood disease. We present a case of a pregnant 40-year-old woman with Henoch-Schonlein purpura, resulting in a viable birth with no fetal complications. Her presentation is discussed in detail and a general presentation of Henoch-Schonlein purpura is explored, with particular attention to its rare onset during pregnancy.
A New Black Fly Species of the Simulium (Gomphostilbia) duolongum Subgroup (Diptera: Simuliidae) From Vietnam, and Molecular Comparisons With Related Species Using the COI Barcoding Gene

Abstract Simulium (Gomphostilbia) yvonneae sp. nov. is described based on adults, pupae, and mature larvae from Vietnam. This new species belongs to the Simulium duolongum subgroup in the S. batoense species-group of the subgenus Gomphostilbia Enderlein. It is distinguished by having a relatively larger number of male upper-eye facets in 16 vertical columns and 16 horizontal rows and a pupal gill with eight filaments arranged as 3+(1+2)+2 from dorsal to ventral, of which two filaments of the ventral pair are 1.8 times as long as the longest filament of the middle and dorsal triplets. Morphological comparisons are made to distinguish this new species from all 22 related species. The genetic distinctiveness of this new species in the S. duolongum subgroup is also presented based on the DNA barcoding COI gene.
Identifying Hypoperfusion in Moyamoya Disease With Arterial Spin Labeling and an [15O]-Water Positron Emission Tomography/Magnetic Resonance Imaging Normative Database

Background and Purpose— Noninvasive imaging of brain perfusion has the potential to elucidate pathophysiological mechanisms underlying Moyamoya disease and enable clinical imaging of cerebral blood flow (CBF) to select revascularization therapies for patients. We used hybrid positron emission tomography (PET)/magnetic resonance imaging (MRI) technology to characterize the distribution of hypoperfusion in Moyamoya disease and its relationship to vessel stenosis severity, through comparisons with a normative perfusion database of healthy controls. Methods— To image CBF, we acquired [15O]-water PET as a reference and simultaneously acquired arterial spin labeling (ASL) MRI scans in 20 Moyamoya patients and 15 age-matched, healthy controls on a PET/MRI scanner. The ASL MRI scans included a standard single-delay ASL scan with postlabel delay of 2.0 s and a multidelay scan with 5 postlabel delays (0.7–3.0s) to estimate and account for arterial transit time in CBF quantification. The percent volume of hypoperfusion in patients (determined as the fifth percentile of CBF values in the healthy control database) was the outcome measure in a logistic regression model that included stenosis grade and location. Results— Logistic regression showed that anterior (P<0.0001) and middle cerebral artery territory regions (P=0.003) in Moyamoya patients were susceptible to hypoperfusion, whereas posterior regions were not. Cortical regions supplied by arteries with stenosis on MR angiography showed more hypoperfusion than normal arteries (P=0.001), but the extent of hypoperfusion was not different between mild-moderate versus severe stenosis. Multidelay ASL did not perform differently from [15O]-water PET in detecting perfusion abnormalities, but standard ASL overestimated the extent of hypoperfusion in patients (P=0.003). Conclusions— This simultaneous PET/MRI study supports the use of multidelay ASL MRI in clinical evaluation of Moyamoya disease in settings where nuclear medicine imaging is not available and application of a normative perfusion database to automatically identify abnormal CBF in patients.
Anthropometric data for wheelchair users: a systematic literature review

The wheelchair user population has special requirements that should be met. However, existing anthropometric data for this specific population are limited. This article characterizes and compares the available literature on anthropometric data of wheelchair users to allow for better understandings and use of data in future studies. A systematic literature review was conducted, where inclusion and exclusion criteria were defined. Forty-one articles were selected to be included in this review. The results show that there is limited information available on wheelchair users’ anthropometrics. There is a lack of consistency between studies, regarding the measurements collected, samples used and methods applied. These methodological issues and differences between studies make it difficult to ensure good comparisons of databases and populations and proper designs of spaces and equipment. This study provides valuable information for future studies that need to use anthropometric data, for research and development of new products targeting wheelchair users.
The Importance of the Coach in Predicting Implicit Beliefs about Skill and Beliefs about the Causes of Success in Handball Players

The objective of the present study was to determine the predictive capacity of the motivational climate generated by coaches and perceived by handball players on implicit beliefs about ability and beliefs about the causes of success in sport. The sample consisted of 444 youth handball players. These players completed the Beliefs about the Causes of Success in Sport Questionnaire, the Conceptions of the Nature of Athletic Ability Questionnaire, Version Two, and the Perceived Motivational Climate in Sport Questionnaire. The structural regression model showed that the mastery climate positively predicted the belief in incremental ability and that this in turn positively predicts both belief in athletic success through effort and ability. The results reflected the importance of the coach in the formative process of the player and the search for performance in sport.
Breath analysis in respiratory diseases: state-of-the-art and future perspectives

ABSTRACT Introduction: The vast majority of respiratory diseases are associated with the production of volatile organic compounds (VOCs), the analysis of which might improve our knowledge about these disorders and their clinical management. The aim of this narrative review is to provide a comprehensive summary of current evidence supporting the application of breath analysis in the field of respiratory diseases, as well as suggesting potential applications available in the near future. Areas covered: A computerized literature search was performed to identify relevant articles reporting original data on the clinical use of breath analysis in respiratory diseases. Papers focusing on diseases other than respiratory, technical issues of VOC sampling and analysis, in vitro experiments or exogenous compounds were excluded. Expert commentary: Currently available evidence on the application of breath analysis in respiratory diseases is encouraging; however, it is mostly based on single-center studies without external validation. The standardization of the technique, together with multicenter clinical trials with external validation, will ensure it is ready for clinical use. Current and new applications in respiratory diseases may represent a major breakthrough in the field, so much so as to deserve further efforts in outlining the most effective way to apply VOC analysis for clinical purposes.
Targeting Ubiquitin Proteasome Pathway with Traditional Chinese Medicine for Treatment of Spinocerebellar Ataxia Type 3.

Nine autosomal dominant spinocerebellar ataxias (SCAs) are caused by an abnormal expansion of CAG trinucleotide repeats that encodes a polyglutamine (polyQ) tract within different genes. Accumulation of aggregated mutant proteins is a common feature of polyQ diseases, leading to progressive neuronal dysfunction and degeneration. SCA type 3 (SCA3), the most common form of SCA worldwide, is characterized by a CAG triplet expansion in chromosome 14q32.1 ATXN3 gene. As accumulation of the mutated polyQ protein is a possible initial event in the pathogenic cascade, clearance of aggregated protein by ubiquitin proteasome system (UPS) has been proposed to inhibit downstream detrimental events and suppress neuronal cell death. In this study, Chinese herbal medicine (CHM) extracts were studied for their proteasome-activating, polyQ aggregation-inhibitory and neuroprotective effects in GFPu and ATXN3/Q 75 -GFP 293/SH-SY5Y cells. Among the 14 tested extracts, 8 displayed increased proteasome activity, which was confirmed by 20S proteasome activity assay and analysis of ubiquitinated and fused GFP proteins in GFPu cells. All the eight extracts displayed good aggregation-inhibitory potential when tested in ATXN3/Q 75 -GFP 293 cells. Among them, neuroprotective effects of five selected extracts were shown by analyses of polyQ aggregation, neurite outgrowth, caspase 3 and proteasome activities, and ATXN3-GFP, ubiquitin, BCL2 and BAX protein levels in neuronal differentiated ATXN3/Q 75 -GFP SH-SY5Y cells. Finally, enhanced proteasome function, anti-oxidative activity and neuroprotection of catalpol, puerarin and daidzein (active constituents of Rehmannia glutinosa and Pueraria lobata) were demonstrated in GFPu and/or ATXN3/Q 75 -GFP 293/SH-SY5Y cells. This study may have therapeutic implication in polyQ-mediated disorders.
Attitudes Towards and Perceptions Regarding the Implementation of Evidence-Based Practice Among Omani Nurses.

Objectives This study aimed to explore the attitudes of Omani nurses towards evidence-based practice (EBP) and their perceptions of the barriers to and facilitators of EBP implementation in Oman. In addition, the attitudes and perceptions of nurse leaders and staff nurses were compared. Methods This descriptive cross-sectional study was conducted between August and October 2016 in three suburban governmental hospitals in Northern Oman. A demographic questionnaire and two EBP instruments were used to collect data from 282 registered Omani nurses, including the Evidence-Based Nursing Attitude Questionnaire and the Developing Evidence-Based Practice Questionnaire. Results A total of 260 Omani nurses took part in the study (response rate: 92.2%). On the whole, the nurses had positive attitudes towards EBP, with no significant difference in mean attitude scores per item between staff nurses and nurse leaders (3.98 ± 0.46 versus 4.03 ± 0.50; P = 0.431). However, in comparison to staff nurses, nurse leaders had higher scores per item for the barriers to changing practice and finding and reviewing evidence subsections, with lower scores for the facilitators to changing practice section. Conclusion In accordance with the international literature, Omani nurses had positive attitudes towards EBP as well as similar perceptions of barriers and facilitators to EBP implementation. These findings may help to inform recommendations for the integration of EBP in educational programmes and clinical settings in Oman, as well as to facilitate necessary changes in nursing practice.
A novel magnetic resonance elastography transducer concept based on a rotational eccentric mass: preliminary experiences with the gravitational transducer

Background. Magnetic resonance elastography (MRE) is used to non-invasively estimate biomechanical tissue properties via the imaging of propagating mechanical shear waves. Several factors including mechanical transducer design, MRI sequence design and viscoelastic reconstruction influence data quality and hence the reliability of the derived biomechanical properties. Purpose. To design and characterize a novel mechanical MRE transducer concept based on a rotational eccentric mass, coined the gravitational transducer. Materials and methods. Table top measurements were performed using accelerometers to characterize the frequency response of the new transducer concept at different driving frequencies (f VIB) and different rotating masses. These were compared to a commercially available pneumatically driven MRE transducer. MR data were acquired on a 3T scanner using a fractionally encoded gradient echo MRE sequence in three healthy volunteers. Acceleration and displacement spectra were plotted in units of g and mm, respectively, and visually compared, emphasizing the ratio between the peaks at f VIB and its 2nd harmonic, a known cause of error in the reconstruction of biomechanical properties as is explored in more detail in numerical simulations here. No formal statistical testing was performed in this proof-of-principle paper. Results. The new transducer concept shows—as expected from theory—a quadratic or linear increase of acceleration amplitude with increase in f VIB or mass, respectively. Furthermore, different versions of the transducer show markedly lower 2nd harmonic-to-f VIB ratios compared to the commercially available pneumatically driven transducer. Displacement was constant over a range of f VIB, in accordance with theory. Phantom and in vivo data show low nonlinearity and excellent data quality. Conclusion. The table top measurements are in concordance with the theory behind a transducer based on a rotational eccentric mass. The resulting constant displacement amplitude irrespective of f VIB and low 2nd harmonic-to-f VIB ratio result in low nonlinearity and high data fidelity in both phantom and in vivo examples.
The Effect of Aging on Memory for Recent and Remote Egocentric and Allocentric Information

ABSTRACT Background: The present study explores recent and well-consolidated spatial memory within the egocentric and allocentric frames of reference in young and elderly people. Methods: The research included young and old participants, within the range of normality. All the participants were tested on four spatial tasks requiring allocentric and egocentric judgments, based on recent as well as remote spatial information, using a Multivariate Regression Analysis. Results: An age effect on both egocentric and allocentric tasks was present in recently learned spatial information. The age effect was not present in tasks regarding well-consolidated spatial information. Finally, sex influenced the performance in allocentric tasks regarding both recent and well-consolidated memory. Conclusion: These data were discussed according to the Multiple Trace Theory, supporting the idea that the magnitude of difference between egocentric and allocentric judgments in aging is somewhat attributable to the characteristic of spatial tasks. In general, a lower difference between the performance of young and elderly participants is shown in tasks based on well-consolidated information when compared with tasks based on episodic information. Well-consolidated information seemed to be better preserved in memory and less prone to the impairment.