bluuebunny/crossref_metadata_2025 huggingface dataset:
Can Functional Nasal Surgery Treat Chronic Headaches? A Systematic Review
Authors: Farmer Rebecca L. , Garg Ravi K. , Afifi Ahmed M.
Published: November 2018

Background:

Nasal surgery is one of the most common operations performed by plastic surgeons. The link between functional nasal surgery and improvement in nasal breathing is well established, but there are other metrics that have been shown to improve as a result of anatomical correction of the nose. Current literature suggests that surgery to remove nasal mucosal contact points can reduce symptoms in chronic headache patients. The authors conducted a systematic literature review to determine the validity of this hypothesis.

Methods:

A systematic search of the literature was performed using the terms “headache,” “rhinogenic headache,” “contact point,” “migraine,” and “surgery/endoscopy.”

Results:

The authors identified 39 articles encompassing a total of 1577 patients who underwent surgery to treat mucosal contact point headaches. Septoplasty and turbinate reduction were the most commonly performed procedures, often in combination with endoscopic sinus surgery. Analysis of the combined data demonstrated improvement in the reported severity of patient symptoms, with 1289 patients (85 percent) reporting partial or complete resolution of headaches postoperatively. Average visual analogue scale scores and number of headache days in patients undergoing nasal surgery were reduced from 7.4 ± 0.9 to 2.6 ± 1.2 (p < 0.001) and 22 ± 4.3 days to 6.4 ± 4.2 days (p = 0.016), respectively. Improvement in headache symptoms was significantly associated with a positive response to preoperative anesthetic testing, and with inclusion of endoscopic sinus surgery as part of the surgery.

Conclusion:

Functional nasal surgery is a viable option to improve headache symptoms in appropriately selected patients.
Googling Aesthetic Plastic Surgery for Patient Insights into the Latest Trends
Authors: Motosko Catherine C. , Zakhem George A. , Saadeh Pierre B. , Hazen Alexes
Published: November 2018

Background:

Analysis of Internet search patterns is rapidly transforming the study of human behavior. Google’s data, accessed through Google Trends, have proven extremely insightful in several fields of medical research. Despite its adoption in other fields of medicine, Google Trends has not yet been explored in the field of plastic surgery.

Methods:

The number of cosmetic surgery procedures from 2005 through 2016 was obtained from the American Society of Plastic Surgeons annual reports. Using Google Trends, the most commonly used keywords describing each procedure were determined, and data regarding search interest over time, interest across geographic area, and Related Queries were obtained. The number of procedures performed annually was compared to relative search volume from the corresponding year and the year prior to determine correlation.

Results:

Of the 22 procedures evaluated, the annual number of eight procedures correlated with Internet search volume in the corresponding year, and six procedures correlated with the Internet searches performed in the year prior. Florida and New York were the states with the most searches for these procedures. Related Queries suggested that several factors, such as operative techniques, notable individuals undergoing procedures, and cost, variably drove correlations for different procedures.

Conclusions:

Google Trends is a powerful tool that can be used to better understand patient interest in, questions about, and decisions regarding cosmetic surgery procedures. These findings warrant action by aesthetic surgeons to increase interest, address misinformation, and help patients fill the gaps of information missed by Internet searches.
Free Ulnar Forearm Flap: Design, Elevation, and Utility in Microvascular Nasal Lining Reconstruction
Authors: Kantar Rami S. , Rifkin William J. , Cammarata Michael J. , Diaz-Siso J. Rodrigo , Farber Scott J. , Rodriguez Eduardo D.
Published: November 2018

Reconstruction of the nasal lining has traditionally been performed using the folded radial forearm free flap, given its reliable blood supply, pliability, and familiarity to surgeons with respect to its harvest. More recently, the free ulnar forearm flap has been proposed as an alternative reconstructive option for the nasal lining, with safe and reliable outcomes, and improved donor-site morbidity compared with its radial counterpart. In this article, the authors provide educational video footage with accompanying text description of the senior author’s (E.D.R) approach to design and elevation of the free ulnar forearm flap for the purpose of reconstructing a composite nasal defect.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
Proliferative Lesions Found at Reduction Mammaplasty: Incidence and Implications in 995 Breast Reductions
Authors: Mastroianni Melissa , Lin Alex , Hughes Kevin , Colwell Amy S.
Published: November 2018

Background:

Reduction mammaplasty relieves symptomatic macromastia. Pathologic specimens occasionally reveal unsuspected proliferative lesions or carcinoma. Few studies examine the incidence, risk factors, and outcomes in this population.

Methods:

A retrospective review was performed between 2000 and 2012. The pathologic condition was categorized as benign, proliferative, or cancer.

Results:

Five hundred seventy-two patients underwent 995 reduction mammaplasties. Cancer was detected in 23 specimens (2.3 percent) and proliferative lesions were detected in 137 (13.8 percent). Compared with patients with benign pathologic findings, patients with proliferative lesions or cancer were older (p < 0.001), had greater body mass index (p = 0.003), had increased unilateral procedures (p < 0.001), and more had history of cancer (p < 0.001). On multivariable regression analysis, age (OR, 1.058; 95 percent CI, 1.040 to 1.077; p < 0.001) and prior breast cancer (OR, 2.070; 95 percent CI, 1.328 to 3.227, p = 0.001) were independent risk factors for proliferative lesions, and age significantly predicted cancer (OR, 1.054; 95 percent CI, 1.012 to 1.097; p = 0.010). Forty-one percent of patients with proliferative lesions and no history of cancer had a change in management. If there was a history of cancer, 54 percent had a change in management.

Conclusions:

Proliferative lesions of the breast may be more common than previously reported. Age and a history of breast cancer increase the risk for proliferative lesions. All should be referred to oncology, as nearly half of these patients will have a change in management.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
3-Dimensional Quantification of Composite Pleural Plaque Volume in Patients Exposed to Asbestos Using High-resolution Computed Tomography
Authors: Dournes Gael , Dubois Adrian , Benlala Ilyes , Lacourt Aude , Paris Christophe , Gislard Antoine , Clin Benedicte , Pairon Jean-Claude , Baldacci Fabien , Laurent François
Published: November 2018

Rationale:

As pleural plaque has been reported as a risk factor in the occurrence of lung cancer and mesothelioma, a reproducible and precise method of measurement of pleural plaque volume (PPV) is needed to further describe these relationships. The aim of the study was to assess the reproducibility of a 3-dimensional computed tomography (3D-CT) volumetric analysis of PPV in patients with occupational exposure to asbestos.

Material and Methods:

A total of 28 patients were retrospectively randomly selected from the multicenter APEXS (Asbestos Post Exposure Survey) study, which was held between 2003 and 2005. All patients underwent a 3D-CT scan. Two readers specialized in chest radiology completed the 3D semiautomated quantification of lung volume using dedicated software. They also had to categorize the visual extent of pleural plaque in terms of thickness and circumference. Reproducibility of the continuous PPV variable was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. Reproducibility of categorical variables was assessed using the κ test.

Results:

Intraobserver reproducibility of PPV was almost perfect (ICC=0.98 [95% interval: 0.97-0.99]), and interobserver reproducibility was very good (ICC=0.93 [0.88-0.97]). At Bland-Altman analysis, the mean differences were 0.1 (limit of agreement: −11.0 to 11.2) and 3.7 cc3 (−17.8 to 25.2), respectively. Visual analysis of both plaque in terms of thickness and circumference were fair to moderate, with κ values ranging from 0.30 to 0.60.

Conclusions:

3D semiautomatic quantification of PPV is feasible and reproducible using CT in patients with occupational exposure to asbestos. PPV measurement may be useful to correlate with other asbestos-related disease outcomes and prognosis.
Hospital Volume Matters
Authors: O’Donnell Thomas F. X. , Boitano Laura T. , Deery Sarah E. , Lancaster Robert T. , Siracuse Jeffrey J. , Schermerhorn Marc L. , Scali Salvatore T. , Patel Virendra I.
Published: November 2018

Objective:

We studied whether the volume–outcome relationship would persist in more complex aortic operations.

Background:

Despite the added complexity of the involvement of the renal arteries in open juxtarenal abdominal aortic aneurysm (AAA) repair, the volume effect in these difficult operations has yet to be defined.

Methods:

We identified all patients in the Vascular Quality Initiative (VQI) who underwent open AAA repair from 2003 to 2016. We calculated each hospital's average annual volume for total open AAA repairs, and total open juxtarenal AAA repairs. We compared adjusted perioperative and long-term survival across quintiles of hospital volume, and constructed models including both volume metrics to evaluate the cross-volume effects.

Results:

Of 8880 total open AAA repairs, there were 3470 open juxtarenal cases. Centers with low (<4), medium (4–14), and high (>14) volumes of open juxtarenal repair demonstrated adjusted perioperative mortality of 9.0%, 4.9%, and 3.9%, respectively (P < 0.01). When both volume metrics were considered, open juxtarenal volume, but not total open AAA volume was associated with perioperative mortality (lowest quintile of juxtarenal volume: OR 2.36 [1.29–4.30], P < 0.01). Hospital volume was not associated with adjusted long-term mortality. High volume centers were more likely to use renal protective strategies such as mannitol and cold renal perfusion (both P < 0.01). Low volume centers performed a similar proportion of cases each year, but 22 centers (13%) did stop performing repairs during the study period.

Conclusion:

Hospitals with low annualized volumes of open juxtarenal repair have higher perioperative mortality, irrespective of their total open aortic volume. Complex open AAA repairs should be performed at experienced centers, and future efforts should focus on centralization of complex aortic care.
Reintervention After Antireflux Surgery for Gastroesophageal Reflux Disease in England
Authors: Markar Sheraz R. , Arhi Chanpreet , Wiggins Tom , Vidal-Diez Alberto , Karthikesalingam Alan , Darzi Ara , Lagergren Jesper , Hanna George B.
Published: November 2018

Background:

After antireflux surgery, highly variable rates of recurrent gastroesophageal reflux disease (GERD) have been reported.

Objective:

To identify the occurrence and risk factors of recurrent GERD requiring surgical reintervention or medication.

Methods:

The Hospital Episode Statistics database was used to identify adults in England receiving primary antireflux surgery for GERD in 2000 to 2012 with follow-up through 2014, and the outcome was surgical reintervention. In a subset of participants, the Clinical Practice Research Datalink was additionally used to assess proton pump inhibitor therapy for at least 6 months (medical reintervention). Risk factors were assessed using multivariable Cox regression providing adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs).

Results:

Among 22,377 patients who underwent primary antireflux surgery in the Hospital Episode Statistics dataset, 811 (3.6%) had surgical reintervention, with risk factors being age 41 to 60 years (HR = 1.22, 95% CI 1.03–1.44), female sex (HR = 1.5; 95% CI 1.3–1.74), white ethnicity (HR = 1.71, 95% CI 1.06–2.77), and low hospital annual volume of antireflux surgery (HR = 1.32, 95% CI 1.04–1.67). Among 2005 patients who underwent primary antireflux surgery in the Clinical Practice Research Datalink dataset, 189 (9.4%) had surgical reintervention and 1192 (59.5%) used proton pump inhibitor therapy, with risk factors for the combined outcome being age >60 years (HR = 2.38, 95% CI 1.81–3.13) and preoperative psychiatric morbidity (HR = 1.58, 95% CI 1.25–1.99).

Conclusion:

At least 3.6% of patients may require surgical reintervention and 59.5% medical therapy following antireflux surgery in England. The influence of patient characteristics and hospital volume highlights the need for patient selection and surgical experience in successful antireflux surgery.
Surgical Treatment of Spontaneous Pneumothorax: Pleural Abrasion or Pleurectomy?
Authors: Ocakcioglu Ilhan , Kupeli Mustafa
Published: November 2018

Purpose:

A primary spontaneous pneumothorax is a condition that occurs predominantly in young and thin male individuals who do not have any history of underlying lung disease. Various techniques such as pleural abrasion and pleurectomy are used to reduce the recurrence rate, but there exists no consensus among surgeons on which surgical technique offers the lowest risk of recurrence.

We aimed to compare the efficiency and recurrence risk of pleural abrasion and pleurectomy methods in patients with primary spontaneous pneumothorax undergoing a wedge resection for the bulleous part of the paranchyme.

Materials and Methods:

Statistically compared variables between the 2 groups were age, sex, symptoms, smoking status, number of previous pneumothorax episodes, surgical indication, bleb number, estimated blood loss, intraoperative complication, duration of the surgery, conversion to open surgery, postoperative drainage amount, chest tube removal time, length of hospital stay, morbidity, mortality, duration of narcotic analgesic usage, pain according to Visual Analog Scale evaluation, follow-up period, and postoperative recurrence.

Results:

The medical records of 88 patients undergoing surgery between 2013 and 2017 were reviewed retrospectively. The pleural abrasion group was superior to the pleurectomy group in terms of operation time, drainage volume, time to drain removal, hospital stay, and Visual Analog Scale pain score on postoperative day 0. Statistically, there was no difference between the pleural abrasion group and the pleurectomy group in the recurrence rates after operation (2.0% vs. 2.5%, respectively; P=0.89).

Conclusions:

Thoracoscopic pleural abrasion is safer than apical pleurectomy and is associated with the same pneumothorax recurrence rate.
Current State of Renal Regenerative Therapies
Authors: Shankar Anusha Shweta , Hoorn Ewout J. , Gribnau Joost , Baan Carla C. , Hoogduijn Martin J.
Published: November 2018

The worldwide increase in the number of patients with end-stage renal disease leads to a growing waiting list for kidney transplantation resulting from the scarcity of kidney donors. Therefore, alternative treatment options for patients with end-stage renal disease are being sought. In vitro differentiation of stem cells into renal tissue is a promising approach to repair nonfunctional kidney tissue. Impressive headway has been made in the use of stem cells with the use of adult renal progenitor cells, embryonic stem cells, and induced pluripotent stem cells for the development toward primitive kidney structures. Currently, efforts are directed at improving long-term maintenance and stability of the cells. This review aims to provide a comprehensive overview of the cell sources used for the generation of kidney cells and strategies used for transplantation in in vivo models. Furthermore, it provides a perspective on stability and safety during future clinical application of in vitro generated kidney cells.
Internal representation of hippocampal neuronal population span a time-distance continuum
Authors: Haimerl Caroline , Angulo-Garcia David , Villette Vincent , Reichinnek Susanne. , Torcini Alessandro , Cossart Rosa , Malvache Arnaud
Published: November 2018

The hippocampus plays a critical role in episodic memory: the sequential representation of visited places and experienced events. This function is mirrored by hippocampal activity that self organizes into sequences of neuronal activation that integrate spatio-temporal information. What are the underlying mechanisms of such integration is still unknown. Single cell activity was recently shown to combine time and distance information; however, it remains unknown whether a degree of tuning between space and time can be defined at the network level. Here, combining daily calcium imaging of CA1 sequence dynamics in running head-fixed mice and network modeling, we show that CA1 network activity tends to represent a specific combination of space and time at any given moment, and that the degree of tuning can shift within a continuum from one day to the next. Our computational model shows that this shift in tuning can happen under the control of the external drive power. We propose that extrinsic global inputs shape the nature of spatio-temporal integration in the hippocampus at the population level depending on the task at hand, a hypothesis which may guide future experimental studies.

Significance Statement

The hippocampus organizes experience in sequences of events that form episodic memory. How are time and space internally computed in the hippocampus in the absence of sequential external inputs? Here we show that time and space are integrated together within the hippocampal network with different degrees of tuning across days. This was found by recording the activity of hundreds of pyramidal cells for several days. We also propose a mechanism supporting such spatio-temporal integration based on a ring attractor network model: the degree of tuning between space and time can be adjusted by modulating the power of a non-sequential external excitatory drive. In this way, the hippocampus is able to generate a spatio-temporal representation tuned to the task at hand.
Parameter Identifiability and Non-Uniqueness In Connectome Based Neural Mass Models
Authors: Xie X. , Kuceyeski A. , Shah S.A. , Schiff N.D. , Nagarajan S.S. , Raj A.
Published: November 2018

The spatial-temporal patterns of neuronal dynamics emerge from the network of coordinated brain regions, this structure-function relationship of the brain can be described mathematically by biophysical models of coupled brain regions connected by white matter tractography. Implementations of such models have focused on reproducing functional connectivity extracted from functional magnetic resonance imaging (fMRI), but these efforts are limited by the temporal resolution of fMRI data and the reduction of time course recordings into phenomenological functional connectivity maps. Here, we optimize parameters of a neural mass model (NMM) to best fit region-wise power spectra across the whole brain estimated from source localized electroencephalography (EEG). NMM models with global parameters were not able to fully reproduce region-wise power spectra, with or without the inclusion of structural connectivity information. In contrast, without the inclusion of structural connectivity information, independent oscillators at each brain region are able to reproduce region-wise power spectra. But the addition of structural connectivity and transmission delays to the NMM does not improve overall power spectra fit. Connectome-based NMM implementations with regional parameters lead to high dimensional network models that produce non-unique results. Inherent parameter identifiability problem in network models poses challenges for using such models as diagnostic tools for neurological diseases.
Bacterial diversity and population dynamics during the fermentation of palm wine from Guerrero Mexico
Authors: Astudillo-Melgar Fernando , Ochoa-Leyva Adrián , Utrilla José , Huerta-Beristain Gerardo
Published: November 2018

Palm wine is obtained by fermentation of palm tree sap. In the Pacific coast of Mexico, palm wine is called Tuba and it is consumed as a traditional fermented beverage. Tuba has empirical applications such as an auxiliary in gastrointestinal diseases and a good source of nutrients. In the present study, a next-generation sequencing of the V3-V4 regions of the 16S rRNA gene was employed to analyze bacterial diversity and population dynamics during the fermentation process of Tuba, both in laboratory controlled conditions and in commercial samples from local vendors. Taxonomic identification showed that Fructobacillus was the main genus in all the samples, following by Leuconostoc, Gluconacetobacter, Sphingomonas, and Vibrio. Alpha diversity analysis demonstrated variability between all the samples. Beta diversity clustered the bacterial population according to the collection origin of the sample. Metabolic functional profile inference showed that the members of the bacterial communities may present the vitamin, antibiotic and antioxidant biosynthesis genes. Additionally, we further investigated the correlation between the predominant genera and some composition parameters of this beverage. This study provides the basis of the bacterial community composition and functionality of the fermented beverage.
Neural Correlates of Optimal Multisensory Decision Making
Authors: Hou Han , Zheng Qihao , Zhao Yuchen , Pouget Alexandre , Gu Yong
Published: November 2018

Perceptual decisions are often based on multiple sensory inputs whose reliabilities rapidly vary over time, yet little is known about how our brain integrates these inputs to optimize behavior. Here we show multisensory evidence with time-varying reliability can be accumulated near optimally, in a Bayesian sense, by simply taking time-invariant linear combinations of neural activity across time and modalities, as long as the neural code for the sensory inputs is close to an invariant linear probabilistic population code (ilPPC). Recordings in the lateral intraparietal area (LIP) while macaques optimally performed a vestibular-visual multisensory decision-making task revealed that LIP population activity reflects an integration process consistent with the ilPPC theory. Moreover, LIP accumulates momentary evidence proportional to vestibular acceleration and visual velocity which are encoded in sensory areas with a close approximation to ilPPCs. Together, these results provide a remarkably simple and biologically plausible solution to optimal multisensory decision making.
Single-cell lineage tracing by endogenous mutations enriched in transposase accessible mitochondrial DNA
Authors: Xu Jin , Nuno Kevin , Litzenburger Ulrike M. , Qi Yanyan , Corces M Ryan , Majeti Ravindra , Chang Howard Y.
Published: November 2018

Simultaneous measurement of cell lineage and cell fates is a longstanding goal in biomedicine. Here we describe EMBLEM, a strategy to track cell lineage using endogenous mitochondrial DNA variants in ATAC-seq data. We show that somatic mutations in mitochondrial DNA can reconstruct cell lineage relationships at single cell resolution with high sensitivity and specificity. Using EMBLEM, we define the genetic and epigenomic clonal evolution of hematopoietic stem cells and their progenies in patients with acute myeloid leukemia. EMBLEM extends lineage tracing to any eukaryotic organism without genetic engineering.
Action perception recruits the cerebellum and is impaired in spinocerebellar ataxia patients
Authors: Abdelgabar Abdel R. , Suttrup Judith , Broersen Robin , Bhandari Ritu , Picard Samuel , Keysers Christian , Zeeuw Chris I. De , Gazzola Valeria
Published: November 2018

Our cerebellum has been proposed to generate prediction signals that may help us plan and execute our motor programs. However, to what extent our cerebellum is also actively involved in perceiving the action of others remains to be elucidated. Using fMRI, we show here that observing goal-directed hand actions of others bilaterally recruits cerebellar Lobules VI, VIIb and VIIIa. Moreover, whereas healthy subjects (n=31) were found to be able to discriminate subtle differences in the kinematics of observed limb movements of others, patients suffering from spinocerebellar ataxia type 6 (SCA6; n=21) were severely impaired in performing such tasks. Our data suggest that the human cerebellum is actively involved in perceiving the kinematics of the hand actions of others and that SCA6 patients’ deficits include a difficulty in perceiving the actions of other individuals. This finding alerts us to the fact that cerebellar disorders can alter social cognition. Given that impairments in social cognition have been reported to be one of the most debilitating consequences of neurological disorders, this finding may be relevant to improving the quality of life of patients and their families.
Genetic effect of type 2 Diabetes to the progression of Neurological Diseases
Authors: Rahman Md Habibur , Peng Silong , Chen Chen , Lio’ Pietro , Moni Mohammad Ali
Published: November 2018

Neurological Diseases (NDs) are progressive disorder often advances with age and comorbidities of Type 2 diabetes (T2D). Epidemiological, clinical and neuropathological evidence advocate that patients with T2D are at an increased risk of getting NDs. However, it is very little known how T2D affects the risk and severity of NDs.

To tackle these problems, we employed a transcriptional analysis of affected tissues using agnostic approaches to identify overlapping cellular functions. In this study, we examined gene expression microarray human datasets along with control and disease-affected individuals. Differentially expressed genes (DEG) were identified for both T2D and NDs that includes Alzheimer Disease (AD), Parkinson Disease (PD), Amyotrophic Lateral Sclerosis (ALS), Epilepsy Disease (ED), Huntington Disease (HD), Cerebral Palsy (CP) and Multiple Sclerosis Disease (MSD).

We have developed genetic association and diseasome network of T2D and NDs based on the neighborhood-based benchmarking and multilayer network topology approaches. Overlapping DEG sets go through protein-protein interaction for hub protein identification and gene enrichment using pathway analysis and gene ontology methods that enhance our understanding of the fundamental molecular procedure of NDs progression.

Gene expression analysis platforms have been extensively used to investigate altered pathways and to identify potential biomarkers and drug targets. Finally, we validated our identified biomarkers using the gold benchmark datasets which identified the corresponding relationship of T2D and NDs. Therapeutic targets aimed at attenuating identified altered pathway could ameliorate neurological dysfunction in a T2D patient.
High Throughput Mechanobiological Screens Enable Mechanical Priming of Pluripotency in Mouse Fibroblasts
Authors: Lee Jason , Ochoa Miguel , Maceda Pablo , Yoon Eun , Samarneh Lara , Wong Mitchell , Baker Aaron B.
Published: November 2018

Transgenic methods for direct reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) are effective in cell culture systems but ultimately limit the utility of iPSCs due to concerns of mutagenesis and tumor formation. Recent studies have suggested that some transgenes can be eliminated by using small molecules as an alternative to transgenic methods of iPSC generation. We developed a high throughput platform for applying complex dynamic mechanical forces to cultured cells. Using this system, we screened for optimized conditions to stimulate the activation of Oct-4 and other transcription factors to prime the development of pluripotency in mouse fibroblasts. Using high throughput mechanobiological screening assays, we identified small molecules that can synergistically enhance the priming of pluripotency of mouse fibroblasts in combination with mechanical loading. Taken together, our findings demonstrate the ability of mechanical forces to induce reprograming factors and support that biophysical conditioning can act cooperatively with small molecules to priming the induction pluripotency in somatic cells.
Action planning modulates the representation of object features in human fronto-parietal and occipital cortex
Authors: Velji-Ibrahim Jena , Crawford J. Douglas , Cattaneo Luigi , Monaco Simona
Published: November 2018

The role of the visual cortex has been extensively studied to determine its role in object recognition but to a lesser degree to determine how action planning influences the representation of objects’ features. We used functional MRI and pattern classification methods to determine if during action planning, object features (orientation and location) could be decoded in an action-dependent way. Sixteen human participants used their right dominant hand to perform movements (Align or Open reach) towards one of two 3D-real oriented objects that were simultaneously presented and placed on either side of a fixation cross. While both movements required aiming toward target location, Align but not Open reach movements required participants to precisely adjust hand orientation. Therefore, we hypothesized that if the representation of object features is modulated by the upcoming action, pre-movement activity pattern would allow more accurate dissociation between object features in Align than Open reach tasks. We found such dissociation in the anterior and posterior parietal cortex, as well as in the dorsal premotor cortex, suggesting that visuomotor processing is modulated by the upcoming task. The early visual cortex showed significant decoding accuracy for the dissociation between object features in the Align but not Open reach task. However, there was no significant difference between the decoding accuracy in the two tasks. These results demonstrate that movement-specific preparatory signals modulate object representation in the frontal and parietal cortex, and to a lesser extent in the early visual cortex, likely through feedback functional connections.
Novel Insight into the Aetiology of Autism Spectrum Disorder Gained by Integrating Expression Data with Genome-wide Association Statistics
Authors: Pain Oliver , Pocklington Andrew J. , Holmans Peter A. , Bray Nicholas J. , O’Brian Heath E. , Hall Lynsey S. , Pardiñas Antonio F. , O’Donovan Michael C. , Owen Michael J. , Anney Richard
Published: November 2018

Background

A recent genome-wide association study (GWAS) of autism spectrum disorders (ASD) (Ncases=18,381, Ncontrols=27,969) has provided novel opportunities for investigating the aetiology of ASD. Here, we integrate the ASD GWAS summary statistics with summary-level gene expression data to infer differential gene expression in ASD, an approach called transcriptome-wide association study (TWAS).

Methods

Using FUSION software, ASD GWAS summary statistics were integrated with predictors of gene expression from 16 human datasets, including adult and fetal brain. A novel adaptation of established statistical methods was then used to test for enrichment within candidate pathways, specific tissues, and at different stages of brain development. The proportion of ASD heritability explained by predicted expression of genes in the TWAS was estimated using stratified linkage disequilibrium-score regression.

Results

This study identified 14 genes as significantly differentially expressed in ASD, 13 of which were outside of known genome-wide significant loci (±500kb). XRN2, a gene proximal to an ASD GWAS locus, was inferred to be significantly upregulated in ASD, providing insight into functional consequence of this associated locus. One novel transcriptome-wide significant association from this study is the downregulation of PDIA6, which showed minimal evidence of association in the GWAS, and in gene-based analysis using MAGMA. Predicted gene expression in this study accounted for 13.0% of the total ASD SNP-heritability.

Conclusion

This study has implicated several genes as significantly up-/down-regulated in ASD providing novel and useful information for subsequent functional studies. This study also explores the utility of TWAS-based enrichment analysis and compares TWAS results with a functionally agnostic approach.
FastqPuri: high-performance preprocessing of RNA-seq data
Authors: Pérez-Rubio Paula , Lottaz Claudio , Engelmann Julia C
Published: November 2018

Background

RNA sequencing (RNA-seq) has become the standard means of analyzing gene and transcript expression in high-throughput. While previously sequence alignment was a time demanding step, fast alignment methods and even more so transcript counting methods which avoid mapping and quantify gene and transcript expression by evaluating whether a read is compatible with a transcript, have led to significant speed-ups in data analysis. Now, the most time demanding step in the analysis of RNA-seq data is preprocessing the raw sequence data, such as running quality control and adapter, contamination and quality filtering before transcript or gene quantification. To do so, many researchers chain different tools, but a comprehensive, flexible and fast software that covers all preprocessing steps is currently missing.

Results

We here present FastqPuri, a light-weight and highly efficient preprocessing tool for fastq data. FastqPuri provides sequence quality reports on the sample and dataset level with new plots which facilitate decision making for subsequent quality filtering. Moreover, FastqPuri efficiently removes adapter sequences and sequences from biological contamination from the data. It accepts both single- and paired-end data in uncompressed or compressed fastq files. FastqPuri can be run stand-alone and is suitable to be run within pipelines. We benchmarked FastqPuri against existing tools and found that FastqPuri is superior in terms of speed, memory usage, versatility and comprehensiveness. Conclusions: FastqPuri is a new tool which covers all aspects of short read sequence data preprocessing. It was designed for RNA-seq data to meet the needs for fast preprocessing of fastq data to allow transcript and gene counting, but it is suitable to process any short read sequencing data of which high sequence quality is needed, such as for genome assembly or SNV (single nucleotide variant) detection. FastqPuri is most flexible in filtering undesired biological sequences by offering two approaches to optimize speed and memory usage dependent on the total size of the potential contaminating sequences. FastqPuri is available at https://github.com/jengelmann/FastqPuri. It is implemented in C and R and licensed under GPL v3.
Evolutionary transition in accessible chromatin landscapes during vertebrate embryogenesis
Authors: Uesaka Masahiro , Kuratani Shigeru , Takeda Hiroyuki , Irie Naoki
Published: November 2018

The relationship between development and evolution is a central topic in evolutionary biology1,2. Recent transcriptome-based studies support the developmental hourglass model, which predicts that the animal embryogenetic program is most strongly conserved at mid-embryonic stages3-9. This model does not necessarily contradict the classical hypothesis10,11that animal development recapitulates its evolutionary history after the mid-embryonic stages2,12. However, to date there is no molecular evidence supporting the hypothesis that gene-expression profiles that are more evolutionarily derived appear sequentially in late development. Here, by estimating activated genomic regions and their evolutionary origins, we show that the recapitulative pattern appears during late embryonic stages. We made a genome-wide assessment of accessible chromatin regions throughout embryogenesis in three vertebrate species (mouse, chicken, and medaka) and determined the phylogenetic range at which these regions were shared. In all three species, sequential activation of putative regulatory regions that were more derived occurred later in embryogenesis, whereas ancestral ones tended to be activated early. Our results clarify the chronologic changes in accessible chromatin landscapes and reveal a phylogenetic hierarchy in the evolutionary origins of putative regulatory regions that parallels developmental stages of activation. This relationship may explain, at least in part, the background for morphological observations of recapitulative events during embryogenesis.
Coherence-based spectro-spatial fillters for stimulus features prediction from electrocorticographic recordings
Authors: Delgado Jaime , Christen Andy , Martin Stephanie , Pasley Brian N. , Knight Robert T. , Giraud Anne-Lise
Published: November 2018

The traditional approach in neuroscience relies on encoding models where brain responses to different stimuli are related to the latter to establish reproducible dependencies. To reduce neuronal and experimental noise, brain signals are usually averaged across trials to detect reliable and coherent brain activity. However, neural representations of stimulus features can be spread over time, frequency, and space, motivating the use of alternative methods that relate stimulus features to brain responses. We propose a Coherence-based spectro-spatial filter method that reconstructs stimulus features from intracortical brain signals. The proposed method models trials of an experiment as realizations of a random process and extracts patterns that are common across brain signals and the presented stimuli. These patterns, originating from different recording sites, are then combined (spatial filtering) to form a final prediction. Our results from three different cognitive tasks (motor movements, speech perception and speech production), concur to show that the proposed method significantly improves the ability to predict stimulus features over traditional methods such as multilinear regression with distributed lags and artificial neural networks. Furthermore, analyses of the model parameters show anatomical discriminability for execution of different motor movements. This anatomical discriminability is also observed in the perception and production of different words. These features could be exploited in the design of neuroprosthesis, as well as for exploring normal brain functioning.
Transitioning between preparatory and precisely sequenced neuronal activity in production of a skilled behavior
Authors: Daliparthi Vamsi K. , Tachibana Ryosuke O. , Cooper Brenton G. , Hahnloser Richard H.R. , Kojima Satoshi , Sober Samuel J. , Roberts Todd F.
Published: November 2018

Precise neural sequences are associated with the production of well-learned skilled behaviors. Yet, how neural sequences arise in the brain remains unclear. In songbirds, premotor projection neurons in the cortical song nucleus HVC are necessary for producing learned song and exhibit precise sequential activity during singing. Using cell-type specific calcium imaging we identify populations of HVC premotor neurons associated with the beginning and ending of singing-related neural sequences. We discovered neurons that bookend singing-related sequences and neuronal populations that transition from sparse preparatory activity prior to song to precise neural sequences during singing. Recordings from downstream premotor neurons or the respiratory system suggest that pre-song activity may be involved in motor preparation to sing. These findings reveal population mechanisms associated with moving from non-vocal to vocal behavioral states and suggest that precise neural sequences begin and end as part of orchestrated activity across functionally diverse populations of cortical premotor neurons.
Neural sensitization improves encoding ﬁdelity in the primate retina
Authors: Appleby Todd R. , Manookin Michael B.
Published: November 2018

An animal’s motion through the environment can induce large and frequent fluctuations in light intensity on the retina. These fluctuations pose a major challenge to neural circuits tasked with encoding visual information, as they can cause cells to adapt and lose sensitivity. Here, we report that sensitization, a short-term plasticity mechanism, solves this difficult computational problem by maintaining neuronal sensitivity in the face of these fluctuations. The numerically dominant output pathway in the macaque monkey retina, the midget (parvocellular-projecting) pathway, undergoes sensitization under specific conditions, including simulated eye movements. Sensitization is present in the excitatory synaptic inputs from midget bipolar cells and is mediated by presynaptic disinhibition from wide-field amacrine cells. Direct physiological recordings and a computational model indicate that sensitization in the midget pathway supports accurate sensory encoding and prevents a loss of responsiveness during dynamic visual processing.
Real-time markerless video tracking of body parts in mice using deep neural networks
Authors: Forys Brandon , Xiao Dongsheng , Gupta Pankaj , Boyd Jamie D , Murphy Timothy H
Published: November 2018

Markerless and accurate tracking of mouse movement is of interest to many biomedical, pharmaceutical, and behavioral science applications. The additional capability of tracking body parts in real-time with minimal latency opens up the possibility of manipulating motor feedback, allowing detailed explorations of the neural basis for behavioral control. Here we describe a system capable of tracking specific movements in mice at a frame rate of 30.3 Hz. To achieve these results, we adapt DeepLabCut – a robust movement-tracking deep neural network framework – for real-time tracking of body movements in mice. We estimate paw movements of mice in real time and demonstrate the concept of movement-triggered optogenetic stimulation by flashing a USB-CGPIO controlled LED that is triggered when real time analysis of movement exceeds a pre-set threshold. The mean time delay between movement initiation and LED flash was 93.44 ms, a latency sufficient for applying behaviorally-triggered feedback. This manuscript presents the rationale and details of the algorithms employed and shows implementation of the system using behaving mice. This system lays the groundwork for a behavior-triggered ‘closed loop’ brain-machine interface with optogenetic stimulation of specific brain regions for feedback.
Influence of serum lead level on prevalence of musculoskeletal pain, quality of life and cardiopulmonary function among welders in Enugu metropolis, Southeast, Nigeria
Authors: Ezema CI , Nwafulume CK , Nweke M. , Eneh OC , Uchenwoke C , Abugu JO , Anyachukwu CC
Published: November 2018

Exposure of welders to welding fumes is a serious occupational health problem all over the world. This often leads to musculoskeletal pain and influences quality of life and cardiopulmonary function, which can be acute or chronic, localized or widespread. The study aimed to assess the serum level of lead and relate it to musculoskeletal pains, quality of life and cardiopulmonary functions of welders in Enugu metropolis, Southeast, Nigeria. Snowball sampling technique was adopted to reach over 100 welders working and residing in Enugu metropolis and who met the inclusion criteria for their informed consent to participate in the study. The first 100 to give the consent were selected for the study. results showed that the mean serum level of lead in welders in Enugu metropolis was 0.522µg/dl with a range of 0.06-1.26 µg/dl. Low back pain was prevalent among welders. The welders had a very high quality of life for the domain of physical health with a score of 94, and high psychosocial and social relationship domains for quality of life with the scores of 69 and 75 respectively. The welders perceived their quality of life as regards environment as average, as they reported their physical environment as being a little or moderately safe, having little money to meet their needs, moderate; availability to information needed for their day to day life, satisfaction with access to health services and time for leisure activities, and a majority reported being satisfied and/or slightly satisfied with their transportation. About 64.2% of the welders had an elevated systolic blood pressure above 120mmHg and 52.6% had diastolic blood pressure elevated above 80mmHg, while only 3.2% of the welders had pulse rates above 100 beats per minute. The mean values for lung function reported for the study were FVC = 1.43, FEV1 = 1.13 and PEF = 1.61. The significant relationship between serum lead levels (FVC, FEV1 and PEF) could be attributed to inhalation. The significant relationship between serum lead levels and low back pain and knee pain could be attributed to lead’s effect on the musculoskeletal system.
Willingness to pay for spectacle among presbyopic population in South Gondar, Ethiopia: A cross-sectional study
Authors: Alemu Haile Woretaw
Published: November 2018

Aim

To assess the willingness to pay for spectacles among the south Gondar presbyopic adult population.

Methods

An interview-based questionnaire was employed to elicit the willingness to pay for spectacles among people refracted during an outreach service at Debre-Tabor Zonal Hospital.

Results

Of the total 322 people participating in the study, only 53.4% (172) were experienced spectacles users. The median gross monthly income of participants was US$ 75.0 (ranged US$ 7.1 - 321.4) and the mean amount of money willing to pa for a pair of spectacles was US$ 17.9 (ranged US$ 1.1-107.1). Participants who were willing to pay US$ 12.5 for a pair of spectacles from a government optical accounted 63.0% (95% CI: 57.8-68.3), while those willing to pay the minimum international pair of spectacle price US$ 5.6 were accounted 73.9% (95% CI: 68.9-79.2%) and spectacle from local private optical price US$ 17.8 accounted 46.6% (95% CI: 40.4-52.2). Multivariate logistic regression analysis indicated factors such as age (P=0.049), occupation (0.001), monthly income (0.001) and history of previous spectacle wear (0.005) to be significantly associated with willingness to pay for a pair of spectacles.

Conclusion

Determining willingness to pay and affordable price could increase spectacle coverage among presbyopic individuals. confirmatory public willingness to pay for a pair of spectacles has to be considered as a useful aspect in establishing affordable and a financially sustainable optical service. The positive willingness to pay for a pair of spectacle has to be supported with accessible provision of spectacles.