bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Methylation Levels in CpGs of the BIN1 Gene in Individuals With Alzheimer Disease
Authors: Salcedo-Tacuma David , Melgarejo Jesús D. , Mahecha Maria F. , Ortega-Rojas Jenny , Arboleda-Bustos Carlos E. , Pardo-Turriago Rodrigo , Arboleda Humberto 
Published: July 2019

Introduction:
Late-onset Alzheimer disease (LOAD) is the most common dementia worldwide. APOE-ɛ4 and BIN1 (Bridging Integrator 1) have been implicated in the pathogenesis of this disease, but, although DNA methylation of dinucleotide CpGs in the BIN1 gene influences alterations, it has not been studied in Hispanics.

Objective:
The objective of this study was to evaluate the BIN1 3′ intergenic region DNA methylation patterns in a Colombian sample of LOAD patients.

Methods:
A case-control study was conducted in 50 individuals with LOAD and 50 age-sex matched controls to determine associations of LOAD with DNA methylation. DNA was isolated from peripheral blood, and methylation levels of 8 CpGs were estimated by bisulfite conversion followed by Sanger sequencing with direct PCR analysis. Logistic regression models adjusted by age, sex, and APOE were used to calculate risk associations between methylation levels and LOAD.

Results:
Overall, participants with LOAD had significantly lower methylation levels on CpG26 (0.86±0.11 vs. 0.95±0.05; P>0.001), CpG44 (0.84±0.09 vs. 0.94±0.06; P=0.001), and CpG87 (0.64±0.12 vs. 0.82±0.10; P>0.001). Adjusted regression models showed that decreased methylation levels of these CpGs remained as risk factors for LOAD (P<0.05).

Conclusions:
Hypomethylation of CpGs in BIN1 might play an important role in the expression of BIN1 and may be a biomarker for identifying individuals at high risk of developing LOAD.
Neurovascular Dysfunction in Alzheimer Disease
Authors: Cipollini Virginia , Sette Giuliano , Bossù Paola , Ciaramella Antonio , Salani Francesca , De Carolis Antonella , Troili Fernanda , Orzi Francesco , Giubilei Franco 
Published: July 2019

Aims:
The aims of this study were to assess vascular dysfunction in patients with Alzheimer disease (AD) by investigating cerebral vasomotor reactivity using transcranial Doppler ultrasound (TCD) and to evaluate any correlations between cerebral vasoreactivity and endothelium dysfunction. Moreover, the frequency of circulating progenitor cells (CPCs) and the blood concentration of vascular/inflammatory markers were evaluated.

Materials and Methods:
We recruited 35 AD subjects and 17 age-matched, sex-matched, and education-matched healthy control subjects. Cerebral vasomotor reactivity was assessed by means of the TCD-based breath-holding index test (BHI). The level of CPCs was evaluated by means of flow cytometry from venous blood samples, while blood vascular/inflammatory markers were measured by means of enzyme-linked immunosorbent assay.

Results:
Both cerebral assay blood flow velocity in the middle cerebral artery (MCAFV) and BHI values were significantly lower in AD subjects than in healthy controls (P<0.05). A positive trend was found between MCAFV and BHI values and Mini-Mental State Evaluation (MMSE) scores. Moreover, the hematopoietic progenitor cells’ count was found to be lower in patients with AD than in controls (P<0.05). Finally, a significantly higher expression of the plasma chemokine CCL-2 was observed in AD patients than in healthy controls.

Conclusions:
Our results confirm that cerebral hemodynamic deterioration may be a critical marker of cognitive decline. Further studies are needed to investigate the role of circulating CPCs and chemokines as potential contributors to neurovascular dysfunction.
Perspectives of African American Older Adults on Brain Health
Authors: Bardach Shoshana H. , Benton Beverly , Walker Charlene , Alfred Doris Love , Ighodaro Eseosa , Caban-Holt Allison , Jicha Gregory A. 
Published: July 2019

Background:
Statistics suggest that African Americans have a disproportionately high prevalence of Alzheimer disease (AD), yet are less likely to enroll in AD clinical trials than white individuals. Although research has previously identified various barriers to participation, relatively little is known about how to overcome these barriers and engage African American individuals in AD research. The purpose of this study is to better understand how African Americans conceptualize brain health and their ability to influence healthy brain aging.

Methods:
Three African American community advocates each facilitated a small group of African American participants over 8 to 10 sessions of a photovoice process involving discussion and sharing of images focused on brain health. Sessions were audiotaped and transcribed verbatim and photographs were uploaded.

Findings:
Participants recognized a diversity of what brain health can mean and indicated an interconnectedness between brain health and its influences. Key factors that were identified by group members as key to brain health included lifestyle factors, activity, and engagement and nature, resiliency, and positivity.

Discussion:
These emic insights into perceptions of brain health may represent important foci for targeted messaging strategies to promote brain health and research engagement within the African American population.
Clinical trials in amyotrophic lateral sclerosis
Authors: McDermott Christopher J. 
Published: July 2019

Purpose of review
To review new developments in the field of amyotrophic lateral sclerosis (ALS) clinical trial design and to review the implications of the latest ALS clinical trials.

Recent findings
There has been substantial reflection on how clinical trials in ALS are best conducted. The revised Airlie House recommendations are an important milestone and should guide trial design. In addition, innovations using individualized risk-based eligibility criteria, adaptive designs, joint modelling, patient-centred approaches, and remote collection of data show real promise. Edaravone was shown to have benefit on function in a well defined subset of patients with ALS, although there are concerns about the generalizability of the findings. Studies of arimoclomol, inosine, and cellular therapies have demonstrated promising signals in early phase work and are being taken forward into larger studies. Well conducted studies of rasagaline did not show an effect on primary outcome measures.

Summary
For many decades there has been regular disappointment with the results of clinical trials. With the innovations in trial design and advances in our basic understanding of the biology of ALS, the prospects for a step change in treatments for people affected by ALS are strong.
Update on amyotrophic lateral sclerosis genetics
Authors: Brenner David , Weishaupt Jochen H. 
Published: July 2019

Purpose of review
The fatal motoneuron disease amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with a high contribution of genetic factors to pathogenesis, in probably both familial and sporadic ALS cases. State-of-the art sequencing techniques continue to reveal novel monogenic causes for ALS, risk factors and modifiers. This leads to an improved genotype/phenotype correlation and is becoming increasingly relevant for genetic diagnosis, counseling and therapy. The first gene-specific therapies are being tested in ongoing clinical trials. Consequently, this review aims to summarize the most important aspects of ALS genetics of the past 2 years.

Recent findings
Most recent disease gene discoveries in the field of ALS constitute the genes KIF5A, ANXA11, GLT8D1 and TIA1, as well as an array of novel risk factors and modifiers. Increasing evidence suggests that even ALS mutations with high penetrance can co-occur with additional mutations in other known ALS genes, suggesting a relevant role of digenetic or polygenetic modes of inheritance. Genotype/phenotype correlation reveals clinical pleiotropy for several ALS genes, which can be linked, for example, to ataxia or Parkinsonian syndromes beyond classical ALS and frontotemporal dementia (FTD) phenotypes.

Summary
The field of ALS continues to develop rapidly with multiple disease gene discoveries per year. The relevance of these findings for genetic counseling and diagnosis is obvious. With gene-specific therapies being tested in a clinical setting, the relevance of genetic aspects of ALS is increasing and likely to be linked to therapeutic consequences in the near future.
Time Is Brain: The Use of EEG Electrode Caps to Rapidly Diagnose Nonconvulsive Status Epilepticus
Authors: McKay Jake H. , Feyissa Anteneh M. , Sener Ugur , D'Souza Caitlin , Smelick Chris , Spaulding Aaron , Yelvington Kirsten , Tatum William O. 
Published: July 2019

Objective:
To perform a feasibility pilot study comparing the usefulness of EEG electrode cap versus standard scalp EEG for acquiring emergent EEGs in emergency department, inpatient, and intensive care unit patients.

Background:
Nonconvulsive status epilepticus (NCSE) is a neurological emergency diagnosed exclusively by EEG. Nonconvulsive status epilepticus becomes more resistant to treatment 1 hour after continued seizure activity. EEG technologists are alerted “stat” when there is immediate need for an EEG during oncall hours, yet delays are inevitable. Alternatively, EEG caps can be quickly placed by in-house residents at bedside for assessment.

Design/Methods:
EEG caps were compared with standard-of-care “stat” EEGs for 20 patients with suspected NCSE. After the order for a stat EEG was placed, neurology residents were simultaneously alerted and placed an EEG cap prior to the arrival of the on-call out-of-hospital technologist. Both EEG cap recordings and standard EEG recordings were visually reviewed at 10 and 20 minutes in a blinded manner by two electroencephalographers. The timing, accuracy of interpretation, and diagnosis between the two techniques were then compared.

Results:
Of the 20 adult patients, 70% (14 of 20) of EEG cap recordings were interpretable, whereas 95% (19 of 20) standard EEGs were interpretable; three had findings consistent with NCSE on both the EEG cap and standard EEG recordings. In the time analysis, 16 patients were included. EEG cap placement was significantly more time efficient than an EEG performed by technologist using the usual “stat” EEG protocol, with the median EEG cap electrode placement occurring 86 minutes faster than standard EEG (22.5 minutes vs. 104.5 minutes; P < 0.0001; n = 16).

Conclusions:
New rapid EEG recording using improved EEG caps may allow for rapid diagnosis and clinical decision making in suspected NCSE.
Automated Processing of Single-Channel Surface Electromyography From Generalized Tonic–Clonic Seizures to Inform Semiology
Authors: Cardenas Damon P. , Halford Jonathan J. , Whitmire Luke E. , Morgan Lola C. , Lie Octavian V. , Jetter Gina M. , Cavazos Jose E. 
Published: July 2019

Purpose:
Advances in surface electromyography (sEMG) monitoring allow for long-term data collection in a natural environment, giving objective information that may identify risk of sudden unexpected death in epilepsy and guide clinical decision-making. Generalized tonic–clonic seizure semiology, namely motor tonic and clonic phase duration, may be an important factor in determining the level of seizure control and risk of sudden unexpected death in epilepsy. This study demonstrates a quantitative analysis of sEMG collected with a dedicated wearable device.

Methods:
During routine monitoring, 23 generalized tonic–clonic seizures from 19 subjects were simultaneously recorded with video-EEG and sEMG. A continuous wavelet-transform was used to determine the frequency components of sEMG recorded during generalized tonic–clonic seizures. An automated process, incorporating a variant of cross-validation, was created to identify ideal frequencies and magnitude ranges for tonic and clonic phases and determine phase durations. Phase durations determined using sEMG analysis were compared with phase durations determined by independent epileptologists' review of video-EEG.

Results:
Cross-validation revealed that the optimal frequency bands for tonic and clonic phases are 150 to 270 Hz and 12 to 70 Hz, respectively. The average difference in phase duration calculated using the two methods for tonic and clonic phases and total seizure duration were −0.42 ± 4.94, −5.12 ± 9.68, and −5.11 ± 11.33 seconds, respectively (results presented are TsEMG − TvEEG, μ ± σ).

Conclusions:
The automated processing of sEMG presented here accurately identified durations of tonic, clonic, and total motor durations of generalized tonic–clonic seizures similar to durations identified by epileptologists' review of video-EEG.
Appliance of Navigated Transcranial Magnetic Stimulation in Radiosurgery for Brain Metastases
Authors: Tokarev Alexey S. , Rak Viacheslav A. , Sinkin Mikhail V. , Evdokimova Olga L. , Stepanov Valentin N. , Koynash Greg V. , Krieg Sandro M. , Krylov Vladimir V. 
Published: July 2019

Purpose:
Navigated transcranial magnetic stimulation (nTMS) provides noninvasive visualization of eloquent brain areas. The nTMS is usually applied in presurgical planning to minimize the risk of surgery-related neurological deterioration. The aim of this study was to evaluate the usefulness of nTMS data for GammaKnife treatment planning for patients suffering from brain metastases.

Methods:
Motor cortex mapping with nTMS was performed in eight patients with brain metastases within or adjacent to the precentral gyrus. The nTMS data set was imported into the planning software and fused with anatomical MRI. Then contouring of the target and critical structures was performed. Treatment plans with and without visualization of the functional structures by nTMS were analyzed and compared by neurosurgeon and medical physicist.

Results:
The primary motor cortex was successfully delineated even in all cases despite significant peritumoral edema. Beam shaping and combined isocenters were used for conformal dose distribution and steeper dose fall-off near the identified eloquent zone. Compared with plans without nTMS data, treatment plans with integration of cortical nTMS mapping data showed a 2% to 78% (mean, 35.2% ± 22.7%) lower 12-Gy volume within the motor cortex without reduction of the dose applied to the tumor.

Conclusions:
The presented approach allows the easy and reliable integration of neurophysiological mapping data into GammaKnife treatment plans by the standard GammaPlan software. Diminishing the dose to critical structures might help to minimize side effects and therefore improve quality of life for brain metastasis patients.
Effect of training on evidence-based practice to undergraduate dental students: pre and postexperimental study
Authors: Wadgave Umesh , Khairnar Mahesh R. , Kadu Tanvi S. , Chadha Gagandeep K. , Wadgave Yogesh 
Published: July 2019

ABSTRACT

Background:
Evidence-based practice (EBP) training is essential for undergraduate students in making sound clinical decisions during patient care. However, EBP training is not included in the curriculum of undergraduate dental students in India and there is a dearth of research that assessed the effectiveness of EBP training in India. Hence, this study aimed to assess the effectiveness of EBP training to dental undergraduate students.

Methods:
Final year undergraduate students and interns of a dental institution participated in this pre and postexperimental study. All the participants received a 2-day workshop (didactic lectures, hands-on and group activities) in a classroom setting. A validated 35 item instrument titled EBP Knowledge, Attitudes, Access and Confidence questionnaire was used for the outcome assessment of EBP training.

Results:
Fifty undergraduate students (33 interns and 17 final year) participated in the study. Statistically significant improvement was observed in six out of 10 items related to EBP knowledge. All the items related to attitude showed a significant positive change in scores. Only four out of nine items related to accessing evidence showed a statistically significant change. Participants reported moderate confidence gain in critical appraisal skills.

Conclusion:
The current study demonstrated moderate improvement in the effectiveness of EBP training in improving EBP knowledge, accessing evidence and critical appraisal skills.
Differential expression of selected microRNA and putative target genes in peripheral blood cells as early markers of severe forms of dengue
Authors: Hapugaswatta Harsha , Amarasena Pubudu , Premaratna Ranjan , Seneviratne Kapila N. , Jayathilaka Nimanthi 
Published: July 2019

AbstractBackgroundDengue presents a wide clinical spectrum including asymptomatic dengue fever (DF) or severe forms, such as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Early symptoms of DHF are similar to those of non-life-threatening DF. Severe symptoms manifest after 3-5 days of fever, which can be life threatening due to lack of proper medications and inability to distinguish severe cases during the early stages. Early prediction of severe dengue in patients with no warning signs who may later develop severe infection is very important for proper disease management to alleviate DHF related complications and mortality. Due to the role in post-transcriptional regulation of gene expression and remarkable stability of microRNA, altered expression of microRNA was evaluated to explore clinically relevant biomarkers.Methodology/Principal findingsThe relative expression of microRNA hsa-let-7e, hsa-miR-30b-5p, hsa-miR-30e-3p, hsa-miR-33a, and hsa-miR-150-5p and several putative target genes in peripheral blood cells (PBC) collected from 20 DF and 20 DHF positive patients within four days from fever onset was evaluated by qRT-PCR. hsa-miR-150-5p showed significant (P<0.05) up regulation in PBC of DHF patients compared to DF patients during the acute phase of infection. Expression of enhancer of zeste homolog 2 (EZH2) was significantly (P<0.05) down regulated indicating that genes involved in epigenetic regulation are also differentially expressed in DHF patients during the early stage of infection.Conclusions/SignificanceDifferential expression of microRNA miR-150-5p and the putative target gene EZH2 may serve as reliable biomarkers of disease severity during early stages of dengue infection.Author summarySevere dengue cannot be distinguished from dengue fever during the early stages of infection based on the clinical symptoms. A diagnosis is only made after the patient is presented with severe manifestations such as plasma leakage and hemorrhage. During a dengue outbreak, this leads to high occupancy of hospital beds. However, only a small percentage of patients present with severe symptoms and the others do not require medical care at a hospital. Therefore, early prognosis of severe manifestations could reduce dengue related mortality by identifying the patients who will benefit from hospitalization and early intervention. We demonstrate that severe dengue in Sri Lankan patients is associated with increased expression of miRNA miR150 and decreased expression of EZH2 during the early stages of infection when none of the patients showed symptoms of developing severe manifestations at later stages of infection.
A pooled analysis of the duration of chemoprophylaxis against malaria after treatment with artesunate-amodiaquine and artemether-lumefantrine
Authors: Bretscher MT , Dahal P , Griffin J , Stepniewska K , Bassat Q , Baudin E , D’Alessandro U , Djimde AA , Dorsey G , Espié E , Fofana B , González R , Juma E , Karema C , Lasry E , Lell B , Lima N , Menéndez C , Mombo-Ngoma G , Moreira C , Nikiema F , Ouédraogo JB , Staedke SG , Tinto H , Valea I , Yeka A , Ghani AC , Guerin PJ , Okell LC 
Published: July 2019

AbstractArtemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ) are the most commonly-used treatments against Plasmodium falciparum malaria in Africa. The lumefantrine and amodiaquine partner drugs may provide differing durations of post-treatment prophylaxis, an important additional benefit to patients. Analyzing 4214 individuals from clinical trials in 12 sites, we estimated a mean duration of post-treatment protection of 13.0 days (95% CI 10.7-15.7) for AL and 15.2 days (95% CI 12.8-18.4) for AS-AQ after allowing for transmission intensity. However, the duration varied substantially between sites: where wild type pfmdr1 86 and pfcrt 76 parasite genotypes predominated, AS-AQ provided ∼2-fold longer protection than AL. Conversely, AL provided up to 1.5-fold longer protection than AS-AQ where mutants were common. We estimate that choosing AL or AS-AQ as first-line treatment according to local drug sensitivity could alter population-level clinical incidence of malaria by up to 14% in under-five year olds where malaria transmission is high.
Analysis of common and rare VPS13C variants in late onset Parkinson disease
Authors: Rudakou Uladzislau , Ruskey Jennifer A. , Krohn Lynne , Laurent Sandra B. , Spiegelman Dan , Greenbaum Lior , Yahalom Gilad , Desautels Alex , Montplaisir Jacques Y. , Fahn Stanley , Waters Cheryl H. , Levy Oren , Kehoe Caitlin M. , Narayan Sushma , Dauvilliers Yves , Dupré Nicolas , Hassin-Baer Sharon , Alcalay Roy N. , Rouleau Guy A. , Fon Edward A. , Gan-Or Ziv 
Published: July 2019

AbstractObjectiveWe aimed to study the role of coding VPS13C variants in a large cohort of late-onset PD (LOPD) patients.MethodsVPS13C and its untranslated regions were sequenced using targeted next-generation sequencing in 1,567 PD patients and 1,667 controls from 3 cohorts. Association tests of rare potential homozygous and compound heterozygous variants and burden tests for rare heterozygous variants were performed. Common variants were analyzed using logistic regression adjusted for age and sex in each of the cohorts, followed by a meta-analysis.ResultsNo bi-allelic carriers of rare VPS13C variants were found among patients and two carriers of compound heterozygous variants were found in two controls. There was no statistically significant burden of rare (MAF<1%) or very rare (MAF<0.1%) coding VPS13C variants in PD. A VPS13C haplotype including the p.R153H-p.I398I-p.I1132V-p.Q2376Q variants was nominally associated with a reduced risk for PD (meta-analysis of the tagging SNP p.I1132V (OR=0.48, 95%CI=0.28-0.82, p=0.0052). This haplotype was not in linkage disequilibrium (LD) with the known genome-wide association study (GWAS) top hit.ConclusionsOur results do not support a role for rare heterozygous or bi-allelic VPS13C variants in LOPD. Additional genetic replication and functional studies are needed to examine the role of the haplotype identified here associated with reduced risk for PD.