bluuebunny/crossref_metadata_2025 huggingface dataset:
Acetyl-l-Carnitine Supplementation and the Treatment of Depressive Symptoms: A Systematic Review and Meta-Analysis
Authors: Veronese Nicola , Stubbs Brendon , Solmi Marco , Ajnakina Olesya , Carvalho Andre F. , Maggi Stefania
Published: October 2017

Objective

Deficiency of acetyl-l-carnitine (ALC) seems to play a role in the risk of developing depression, indicating a dysregulation of fatty acid transport across the inner membrane of mitochondria. However, data about ALC supplementation in humans are limited. We thus conducted a systematic review and meta-analysis investigating the effect of ALC on depressive symptoms across randomized controlled trials (RCTs).

Methods

A literature search in major databases, without language restriction, was undertaken from inception until 30 December 2016. Eligible studies were RCTs of ALC alone or in combination with antidepressant medications, with a control group taking placebo/no intervention or antidepressants. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were used for summarizing outcomes with a random-effect model.

Results

Twelve RCTs (11 of which were ALC monotherapy) with a total of 791 participants (mean age = 54 years, % female = 65%) were included. Pooled data across nine RCTs (231 treated with ALC versus 216 treated with placebo and 20 no intervention) showed that ALC significantly reduced depressive symptoms (SMD = −1.10, 95% CI = −1.65 to −0.56, I
2 = 86%). In three RCTs comparing ALC versus antidepressants (162 for each group), ALC demonstrated similar effectiveness compared with established antidepressants in reducing depressive symptoms (SMD = 0.06, 95% CI = −0.22 to 0.34, I
2 = 31%). In these latter RCTs, the incidence of adverse effects was significantly lower in the ALC group than in the antidepressant group. Subgroup analyses suggested that ALC was most efficacious in older adults.

Conclusions

ALC supplementation significantly decreases depressive symptoms compared with placebo/no intervention, while offering a comparable effect with that of established antidepressant agents with fewer adverse effects. Future large scale trials are required to confirm/refute these findings.
Primary Pericardial Angiosarcoma Shown on FDG PET/CT
Authors: Shi Ximin , Li Fang
Published: October 2017

A 63-year-old woman had persistent bloody pericardial effusion. Tuberculous pericarditis was initially suspected, but empirical antituberculosis therapy was futile. FDG PET/CT study revealed abnormal FDG activity in multiple parts of the pericardium, especially along with aorta and main pulmonary artery, and in the left atrium. However, there was no abnormal activity in other parts of the body. Histopathologic examination revealed primary pericardial angiosarcoma.
68Ga-DOTA-TATE PET/CT for Molecular Imaging of Somatostatin Receptor Expression in Extra-adrenal Paraganglioma in a Case of Complete Carney Triad
Authors: Derlin Thorsten , Hartung Dagmar , Hueper Katja
Published: October 2017

Carney triad is a very rare syndrome characterized by the synchronous or metachronous occurrence of gastrointestinal stromal tumors, pulmonary chondroma, and extra-adrenal paraganglioma. We present the case of a 36-year-old woman with complete Carney triad who underwent a 68Ga-DOTA-TATE PET/CT scan for restaging of metastasizing extra-adrenal paraganglioma and for evaluation of targeted radionuclide therapy potential. On the 68Ga-DOTA-TATE PET scan, increased tracer accumulation was observed in paraganglioma metastases. This case highlights the usefulness of 68Ga-DOTA-TATE PET/CT for restaging of metastasizing paraganglioma in Carney triad and the option of targeted radionuclide therapy in this entity.
Absent Cerebellar Circulation With Intact Cerebral Blood Flow on a 99mTc Bicisate “Brain Death” Study
Authors: Schmidt Matthew Q. , Schraml Frank V.
Published: October 2017

A 55-year old woman presented in an obtunded state and was found to have a subarachnoid hemorrhage. After endovascular repair, her condition deteriorated, and brain death was suspected. A 99mTc bicisate brain blood flow study was performed, which showed a complete absence of blood flow to the cerebellum despite intact circulation to the cerebral hemispheres. These atypical findings are likely a result of a transient intracranial pressure differential and the timing of the study. A timely and accurate declaration of brain death has important psychosocial and ethical implications, particularly when organ donation is being considered.
Benign Traumatic Rib Fracture
Authors: Jochumsen Mads Ryø , Dias André H. , Bouchelouche Kirsten
Published: October 2017

Two, respectively, 72- and 76-year-old men with recently diagnosed high-risk prostate cancer were referred for primary staging with 68Ga–prostate-specific membrane antigen (PSMA) PET/CT. In both patients, the PET scans revealed increased 68Ga-PSMA uptake in, respectively, 3 and 4 rib fractures, characteristically placed as “pearls on a string.” These cases illustrate important pitfalls when reporting PSMA PET.
FDG PET/CT in Immunoglobulin G4–Related Spinal Hypertrophic Pachymeningitis
Authors: Zhao Qian , Dong Aisheng , Bai Yushu , Wang Yang , Zuo Changjing
Published: October 2017

A 49-year-old woman complained of right upper back pain for 1 month. Serum tests showed increased erythrocyte sedimentation rate. Thoracic spinal MRI showed an epidural lesion at the T1–T4 level with inhomogeneous signal intensity on T2-weighted images, slightly higher signal intensity than spinal cord on T1-weighted images, and remarkable enhancement on enhanced T1-weighted images. Epidural malignant tumor was suspected. FDG PET/CT was performed showing increased FDG uptake of the lesion extending to the right T1–T2 and T2–T3 neural foramina. A decompressive posterior thoracic laminectomy with the lesion resection was performed. Immunoglobulin G4–related spinal hypertrophic pachymeningitis was confirmed by pathology.
18F-FDG PET for Detection of Primary Tracheobronchial T-/Natural Killer–Cell–Derived Posttransplant Lymphoproliferative Disorder After Lung Transplantation
Authors: Derlin Thorsten , Braubach Peter , Kreipe Hans Heinrich , Hueper Katja
Published: October 2017

Posttransplant lymphoproliferative disorder (PTLD) is a rare, but potentially devastating complication of solid organ transplantation. Epstein-Barr virus–associated PTLDs of T-cell origin are exceedingly rare. We present the case of a 20-year-old man with extranasal T-/natural killer–cell–derived PTLD after lung transplantation who underwent an 18F-FDG PET/CT scan for staging of disease. The 18F-FDG-PET scan demonstrated an unusual pattern of lymphomatous involvement limited to the recipients tracheobronchial tree without concomitant involvement of the donor's bronchi. This case highlights the potential of 18F-FDG PET/CT for sensitive detection and staging of uncommon manifestations of PTLD.
Comparison Between Different PET and CT-Based Imaging Interpretation Criteria at Interim Imaging in Patients With Diffuse Large B-Cell Lymphoma
Authors: Baratto Lucia , Davidzon Guido A. , Moghbel Mateen , Hatami Negin , Iagaru Andrei , Mittra Erik S.
Published: October 2017

Objective

To evaluate the predictive value of interim PET (iPET) in diffuse large B-cell lymphoma (DLBCL) using 5 different imaging interpretation criteria: Deauville 5-point scale criteria, International Harmonization Project (IHP) criteria, Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, European Organization for Research and Treatment of Cancer, and PET Response Criteria in Solid Tumors (PERCIST) 1.0.

Methods

We retrospectively reviewed records from 38 patients with DLBCL who underwent baseline and iPET at our institution. Imaging was interpreted according to the previously mentioned criteria. Results were correlated with end-of-treatment response, based on reports at the end of treatment radiological examinations, overall survival (OS), and progression-free survival (PFS) to assess and compare the predictive value of iPET according to each criterion. We also evaluated the concordance between different criteria.

Results

The Deauville and PERCIST criteria were the most reliable for predicting end-of-treatment response, reporting an accuracy of 81.6%. They also correlated with OS and PFS (P = 0.0004 and P = 0.0001, and P = 0.0007 and P = 0.0002, for Deauville and PERCIST, respectively). Interim PET according to European Organization for Research and Treatment of Cancer also predicted the end-of-treatment response with an accuracy of 73.7% and had a significant correlation with OS (P = 0.007) and PFS (P = 0.007). In contrast, the IHP criteria and RECIST did not predict outcomes: the accuracy for end-of-treatment response was 34.2% and 36.8%, respectively, with no significant correlation with OS or PFS (P = 0.182 and P = 0.357, and P = 0.341 and P = 0.215, for OS and PFS, respectively).

Conclusions

The predictive value of iPET in DLBCL patients is most reliable using the Deauville and PERCIST criteria. Criteria that rely on anatomical characteristics, namely, RECIST and IHP criteria, are less accurate in predicting patient outcomes in DLBCL.
Uptake of 68Ga–Prostate-Specific Membrane Antigen PET in Adrenal Gland
Authors: Strele-Trieb Pia , Dunzinger Andreas , Sonnberger Michael , Wolfsgruber Johannes , Pichler Robert
Published: October 2017

A 76-year-old man with prostate cancer pT2c N0 M0 R1 GS9 (4+5) operated 2009 and radiated postoperatively underwent restaging by 68Ga-PSMA-PET in January 2017 because of PSA rise at 0.44 ng/ml under medication with GnRH analogues. An intense focal uptake of the diffusely enlarged left adrenal gland was observed as the only pathological finding. Further evaluation by MRI imaging revealed a plump left adrenal gland with a relatively enlarged diameter of 2 cm and excluded tumor and nodular hyperplasia as well. Without any change of the therapeutic regime the patient presented in July 2017 with a PSA level of 0.05 ng/ml and no sign of cancer progress.
Compatibility of ZOLL Defibrillators in Simulation-Based Training
Authors: Shoemaker Jamie Leigh , Duty Olivia T. , Martin Kenneth J. , Geis Gary L.
Published: October 2017

Introduction

In response to the need for high-quality cardiopulmonary resuscitation (CPR) during cardiac arrest, our institution recently purchased ZOLL R Series monitor/defibrillators. This defibrillator provides CPR quality metrics and displays a filtered rhythm through compressions. Purchase of this defibrillator resulted in a practice change and heavily impacted our simulation-based training courses by requiring providers to practice CPR and defibrillation in as close to the real environment as possible. Thus, our objective was to determine which commercial simulators would be compatible with the ZOLL R Series defibrillator system and its CPR feedback functionality in a simulation-based training setting.

Methods

Our simulation center uses primarily Gaumard Scientific and Laerdal Medical simulators ranging in size from neonate to adult. Through an iterative process in the laboratory, we evaluated if, and to what level, the CPR display metrics, filtered rhythm, and idle time display could be demonstrated with CPR on the different simulators using infant, pediatric, and adult pads.

Results

Certain simulators allow demonstration and real-time practice of defibrillator functions better than others with the ZOLL R Series system when used in the context of CPR training. We have no high-fidelity infant-sized simulators that can meet the depth recommendation for chest compressions given by the American Heart Association. Ventricular fibrillation is the only rhythm that offers a filtered option. Idle time can be reliably displayed for simulators where CPR is detected.

Conclusions

When a primary learning objective for simulation-based training involves training on the ZOLL R Series defibrillator, there are a limited number of simulators and rhythms that can accurately represent its features.
A multicenter evaluation of the optimal timing of surgical stabilization of rib fractures
Authors: Pieracci Fredric M. , Coleman Julia , Ali-Osman Francis , Mangram Alicia , Majercik Sarah , White Thomas W. , Jeremitsky Elan , Doben Andrew R.
Published: October 2017

BACKGROUND

The optimal timing of surgical stabilization of rib fractures (SSRF) remains debated. We hypothesized that (1) demographic, radiologic, and clinical variables are associated with time to surgery and (2) shorter time to SSRF improves acute outcomes.

METHODS

Prospectively collected SSRF databases from four trauma centers were merged and analyzed (2006–2016). The independent variable was days from hospital admission to SSRF (early [<1 day], mid [1–2 days], and late [3–10 days]). Outcomes included length of operation, number of ribs repaired, prolonged (>24 hours) mechanical ventilation, pneumonia, tracheostomy, length of stay, and mortality. Multivariable logistic regression was used to control for significant differences in covariates between groups.

RESULTS

Five hundred fifty-one patients were analyzed. The median time to SSRF was 1 day (range, 0–10); 207 (37.6%) patients were in the early group, 168 (30.5%) in the midgroup, and 186 (31.9%) in the late group. There was a significant shift toward earlier SSRF over the study period. Time to SSRF was significantly associated with study center (p < 0.01), year of surgery (p < 0.01), age (p = 0.02), mechanism of injury (p = 0.04), and body mass index (p = 0.02). Injury severity was not associated with time to surgery. Despite repairing the same median number of ribs (4; range, 1–13), median length of surgery was 68 minutes longer for the late as compared to the early group (p < 0.01). After controlling for the aforementioned significant covariates, each additional hospital day before SSRF was independently associated with a 31% increased likelihood of pneumonia (p < 0.01), a 27% increased likelihood of prolonged mechanical ventilation (p < 0.01), and a 26% increased likelihood of tracheostomy (p < 0.01).

CONCLUSION

Surgical stabilization of rib fractures within 1 day of admission is associated with certain demographic and physiologic variables. After controlling for confounding factors, early SSRF was accomplished using less operative time, and was associated with favorable outcomes. When indicated and feasible, SSRF should occur as early as possible.

Level of evidence

Therapy, level III.
Food Safety Practices of Homebound Seniors Receiving Home-Delivered Meals
Authors: McWilliams Rita M. , Hallman William K. , Cuite Cara L. , Senger-Mersich Angela , Sastri Natasha , Netterville Linda , Byrd-Bredbenner Carol
Published: October 2017

Little is known about the food safety knowledge, behaviors, environments, and in-home food supplies of the growing population of homebound US seniors who are dependent on home-delivered meals. This cross-sectional study of 725 home-delivered meal recipients used in-home interviews, food inventories, and kitchen audits to examine potential food safety vulnerabilities. Seniors' food safety was compromised by poor home kitchen conditions, inadequate refrigerator/freezer temperatures, vision problems, and a lack of understanding of safe food storage times. The results identify conditions that may place seniors at greater risk for foodborne disease and suggest areas for interventions to reduce this risk.
Drug-Induced Xerostomia in Hemodialysis Patients and Its Implications in Oral Health
Authors: Torres Roxana , Brunetti Luigi , Morrow Ellis , Ziegler Jane
Published: October 2017

Xerostomia or dry mouth occurs when there is decreased production of saliva. This condition can lead to oral health complications (eg, dental caries, oral lesions), chewing and swallowing problems, and reduced quality of life. Hemodialysis patients are at increased risk of developing xerostomia because of polypharmacy, fluid restriction, salivary gland dysfunction, oral breathing, and systemic diseases. Drug-induced xerostomia increases the risk of oral diseases in these patients. The health care team needs to assess the symptoms of xerostomia in the hemodialysis population and to apply the latest recommendations for its management. This article describes the risks of drug-induced xerostomia in oral health and its management in patients on HD.
Socioeconomic Disparities and Sexual Dimorphism in Neurotoxic Effects of Ambient Fine Particles on Youth IQ: A Longitudinal Analysis
Authors: Wang Pan , Tuvblad Catherine , Younan Diana , Franklin Meredith , Lurmann Fred , Wu Jun , Baker Laura A , Chen Jiu-Chiuan
Published: October 2017

Mounting evidence indicates that early-life exposure to particulate air pollutants pose threats to children’s cognitive development, but studies about the neurotoxic effects associated with exposures during adolescence remain unclear. We examined whether exposure to ambient fine particles (PM2.5) at residential locations affects intelligence quotient (IQ) during pre-/early-adolescence (ages 9-11) and emerging adulthood (ages 18-20) in a demographically-diverse population (N = 1,360) residing in Southern California. Increased ambient PM2.5levels were associated with decreased IQ scores. This association was more evident for Performance IQ (PIQ), but less for Verbal IQ, assessed by the Wechsler Abbreviated Scale of Intelligence. For each inter-quartile (7.73 μg/m3) increase in one-year PM2.5preceding each assessment, the average PIQ score decreased by 3.08 points (95% confidence interval = [−6.04, −0.12]) accounting for within-family/within-individual correlations, demographic characteristics, family socioeconomic status (SES), parents’ cognitive abilities, neighborhood characteristics, and other spatial confounders. The adverse effect was 150% greater in low SES families and 89% stronger in males, compared to their counterparts. Better understanding of the social disparities and sexual dimorphism in the adverse PM2.5-IQ effects may help elucidate the underlying mechanisms and shed light on prevention strategies.
Use of a scoring strategy to determine clinical risk of progression and risk group-specific treatment adherence in subjects with latent tuberculosis infection
Authors: Scolarici Michael , Dekitani Ken , Chen Ling , Sokol-Anderson Marcia , Hoft Daniel F , Chatterjee Soumya
Published: October 2017

Background

Annual incidence of active tuberculosis (TB) cases has plateaued in the US from 2013-2015. Most cases are from reactivation of latent tuberculosis infection (LTBI). A likely contributor is suboptimal LTBI treatment completion rates in subjects at high risk of developing active TB. It is unknown whether these patients are adequately identified and treated under current standard of care.

Methods

In this study, we sought to retrospectively assess the utility of an online risk calculator (tstin3d.com) in determining probability of LTBI and defining the characteristics and treatment outcomes of Low: 0-<10%, Intermediate: 10-<50% and High: 50-100% risk groups of asymptomatic subjects with LTBI seen between 2010-2015.

Results

51(41%), 46 (37%) and 28 (22%) subjects were in Low, Intermediate and High risk groups respectively. Tstin3d.com was useful in determining the probability of LTBI in tuberculin skin test positive US born subjects. Of 114 subjects with available treatment information, overall completion rate was 61% and rates of completion in Low (60%), Intermediate (63%) and High (57%) risk groups were equivalent. 75% subjects in the 3HP group completed treatment compared to 58% in the INH group. Provider documentation of important clinical risk factors was often incomplete. Logistic regression analysis showed no clear trends of treatment completion being associated with assessment of a risk factor.

Conclusion

These findings suggest tstin3d.com could be utilized in the US setting for risk stratification of patients with LTBI and select treatment based on risk. Current standard of care practice leads to subjects in all groups finishing treatment at equivalent rates.
A fine-tuned vector-parasite dialogue in tsetse’s cardia determines peritrophic matrix integrity and trypanosome transmission success
Authors: Vigneron Aurélien , Aksoy Emre , Weiss Brian L , Bing Xiaoli , Zhao Xin , Awuoche Erick O , O’Neill Michelle , Wu Yineng , Attardo Geoffrey M , Aksoy Serap
Published: October 2017

Arthropod vectors have multiple physical and immunological barriers that impede the development and transmission of parasites to new vertebrate hosts. These barriers include the peritrophic matrix (PM), a chitinous barrier that separates the blood bolus from the midgut epithelia and inturn, modulates vector-microbiota interactions. In tsetse flies, a sleeve-like PM is continuously produced by the cardia organ located at the fore- and midgut junction. African trypanosomes, Trypanosoma brucei, must bypass the PM twice; first to colonize the midgut and secondly to reach the salivary glands (SG), to complete their transmission cycle in tsetse. However, not all flies with midgut infections develop mammalian transmissible SG infections - the reasons for which are unclear. Here, we used transcriptomics, microscopy and functional genomics analyses to understand the factors that regulate parasite migration from midgut to SG. In flies with midgut infections only, parasites fail to cross the PM as they are eliminated from the cardia by reactive oxygen intermediates (ROIs) - albeit at the expense of collateral cytotoxic damage to the cardia. In flies with midgut and SG infections, expression of genes encoding components of the PM is reduced in the cardia, and structural integrity of the PM barrier is compromised. Under these circumstances trypanosomes traverse through the newly secreted and compromised PM. The process of PM attrition that enables the parasites to re-enter into the midgut lumen is apparently mediated by components of the parasites residing in the cardia. Thus, a fine-tuned dialogue between tsetse and trypanosomes at the cardia determines the outcome of PM integrity and trypanosome transmission success.

Author summary

Insects are responsible for transmission of parasites that cause deadly diseases in humans and animals. Understanding the key factors that enhance or interfere with parasite transmission processes can result in new control strategies. Here, we report that a proportion of tsetse flies with African trypanosome infections in their midgut can prevent parasites from migrating to the salivary glands, albeit at the expense of collateral damage. In a subset of flies with gut infections, the parasites manipulate the integrity of a midgut barrier, called the peritrophic matrix, and reach the salivary glands for transmission to the next mammal. Either targeting parasite manipulative processes or enhancing peritrophic matrix integrity could reduce parasite transmission.
How emotional memory affects face remembering: an ERP investigation
Authors: Proverbio Alice Mado , Vanutelli Maria Elide , Viganò Simone
Published: October 2017

It is known that the longer an information has been memorized, the stronger is its memory trace. At the same time it is known that the emotionally-valenced information has a stronger memory trace than neutral one. Interactive effects between these factors are largely unknown. In this study electrical neuroimaging signals were recorded in healthy controls to explore the neural mechanism of memory for faces of different emotional valence, sex, learning context and temporal recency. In a study phase participants familiarized with the fictional police dossier of 10 victims of dramatic deaths including homicide or earthquake (depicted as attractive and nice persons of about 45 years), twice a day for seven days before EEG recordings. Hundreds of famous movie stars (overlearned), victims (recent) and new faces were presented in an old/new recognition task. ERP responses showed a modulation of anterior N2 and FN400 as a function of face familiarity (with no differences between overlearned and recent faces), while parietal late positivity was sensitive to engram temporal recency (it was much larger to overlearned than recent faces, paralleling behavioral data). However, LP amplitude did not differ to overlearned vs. recent same-sex faces, showing how emotional memory can enhance faces remembering. A late frontal negativity revealed sensitive to source memory.
An information-theoretic perspective on the costs of cognition
Authors: Alexandre Zénon , Oleg Solopchuk , Giovanni Pezzulo
Published: October 2017

In statistics and machine learning, model accuracy is traded off with complexity, which can be viewed as the amount of information extracted from the data. Here, we discuss how cognitive costs can be expressed in terms of similar information costs, i.e. as a function of the amount of information required to update a person’s prior knowledge (or internal model) to effectively solve a task. We then examine the theoretical consequences that ensue from this assumption. This framework naturally explains why some tasks – for example, unfamiliar or dual tasks – are costly and permits to quantify these costs using information-theoretic measures. Finally, we discuss brain implementation of this principle and show that subjective cognitive costs can originate either from local or global capacity limitations on information processing or from increased rate of metabolic alterations. These views shed light on the potential adaptive value of cost-avoidance mechanisms.
Heritability of regional brain volumes in large-scale neuroimaging and genetic studies
Authors: Zhao Bingxin , Ibrahim Joseph G. , Li Yun , Li Tengfei , Wang Yue , Shan Yue , Zhu Ziliang , Zhou Fan , Zhang Jingwen , Huang Chao , Liao Huiling , Yang Liuqing , Thompson Paul M. , Zhu Hongtu ,   Pediatric Imaging, Neurocognition and Genetics (PING), McCabe Connor , Chang Linda , Akshoomoff Natacha , Newman Erik , Ernst Thomas , Van Zijl Peter , Kuperman Joshua , Murray Sarah , Bloss Cinnamon , Appelbaum Mark , Gamst Anthony , Thompson Wesley , Bartsch Hauke ,   Alzheimer’s Disease Neuroimaging Initiative (ADNI), Weiner Michael , Aisen Paul , Petersen Ronald , Jack Clifford R. , Jagust William , Trojanowki John Q. , Toga Arthur W. , Beckett Laurel , Green Robert C. , Saykin Andrew J. , Morris John , Shaw Leslie M. , Khachaturian Zaven , Sorensen Greg , Carrillo Maria , Kuller Lew , Raichle Marc , Paul Steven , Davies Peter , Fillit Howard , Hefti Franz , Holtzman Davie , Mesulman M. Marcel , Potter William , Snyder Peter J. , Schwartz Adam , Montine Tom , Thomas Ronald G. , Donohue Michael , Walter Sarah , Gessert Devon , Sather Tamie , Jiminez Gus , Harvey Danielle , Bernstein Matthew , Fox Nick , Thompson Paul , Schuff Norbert , DeCarli Charles , Borowski Bret , Gunter Jeff , Senjem Matt , Vemuri Prashanthi , Jones David , Kantarci Kejal , Ward Chad , Koeppe Robert A. , Foster Norm , Reiman Eric M. , Chen Kewei , Mathis Chet , Landau Susan , Cairns Nigel J. , Householder Erin , Taylor-Reinwald Lisa , Lee Virginia M.Y. , Korecka Magdalena , Figurski Michal , Crawford Karen , Neu Scott , Foroud Tatiana M. , Potkin Steven , Shen Li , Faber Kelley , Kim Sungeun , Nho Kwangsik , Thal Leon , Frank Richard , Buckholtz Neil , Albert Marilyn , Hsiao John
Published: October 2017

Brain genetics is an active research area. The degree to which genetic variants impact variations in brain structure and function remains largely unknown. We examined the heritability of regional brain volumes (p ~ 100) captured by single-nucleotide polymorphisms (SNPs) in UK Biobank (n ~ 9000). We found that regional brain volumes are highly heritable in this study population. We observed omni-genic impact across the genome as well as enrichment of SNPs in active chromatin regions. Principal components derived from regional volume data are also highly heritable, but the amount of variance in brain volume explained by the component did not seem to be related to its heritability. Heritability estimates vary substantially across large-scale functional networks and brain regions. The variation in heritability across regions was not related to measurement reliability. Heritability estimates exhibit a symmetric pattern across left and right hemispheres and are consistent in females and males. Our main findings in UK Biobank are consistent with those in Alzheimers Disease Neuroimaging Initiative (n ~ 1100), Philadelphia Neurodevelopmental Cohort (n ~ 600), and Pediatric Imaging, Neurocognition, and Genetics (n ~ 500) datasets, with more stable estimates in UK Biobank.
Invariances in a combinatorial olfactory receptor code
Authors: Si Guangwei , Kanwal Jessleen K. , Hu Yu , Tabone Christopher J. , Baron Jacob , Berck Matthew , Vignoud Gaetan , Samuel Aravinthan D.T.
Published: October 2017

Animals can identify an odorant type across a wide range of concentrations, as well as detect changes in concentration for individual odorant type. How olfactory representations are structured to support these functions remains poorly understood. Here, we studied how a full complement of ORNs in the Drosophila larva encodes a broad input space of odorant types and concentrations. We find that dose-response relationships across odorants and ORN types follow the Hill function with shared cooperativity but different activation thresholds. These activation thresholds are drawn from a power law statistical distribution. A fixed activation function and power law distribution of activation thresholds underlie invariances in the encoding of odorant identity and intensity. Moreover, we find similar temporal response filters of ORNs across odorant types and concentrations. Such uniformity in the temporal filter may allow identity invariant coding in fluctuating or turbulent odor environments. Common patterns in ligand-receptor binding and sensory transduction across olfactory receptors may give rise to these observed invariances in the olfactory combinatorial code. Invariant patterns in the activity responses of individual ORNs and the ORN ensemble may simplify decoding by downstream circuits.
Decomposing parietal memory reactivation to predict consequences of remembering
Authors: Lee Hongmi , Samide Rosalie , Richter Franziska R. , Kuhl Brice A.
Published: October 2017

Memory retrieval can strengthen, but also distort memories. Parietal cortex is a candidate region involved in retrieval-induced memory changes as it reflects retrieval success and represents retrieved content. Here, we conducted an fMRI experiment to test whether different forms of parietal reactivation predict distinct consequences of retrieval. Subjects studied associations between words and pictures of faces, scenes, or objects, and then repeatedly retrieved half of the pictures, reporting the vividness of the retrieved pictures (‘retrieval practice’). On the following day, subjects completed a recognition memory test for individual pictures. Critically, the test included lures highly similar to studied pictures. Behaviorally, retrieval practice increased both hit and false alarm rates to similar lures, confirming a causal influence of retrieval on subsequent memory. Using pattern similarity analyses, we measured two different levels of reactivation during retrieval practice: generic ‘category-level’ reactivation and idiosyncratic ‘item-level’ reactivation. Vivid remembering during retrieval practice was associated with stronger category- and item-level reactivation in parietal cortex. However, these measures differentially predicted subsequent recognition memory performance: whereas higher category-level reactivation tended to predict false alarms to lures, item-level reactivation predicted correct rejections. These findings indicate that parietal reactivation can be decomposed to tease apart distinct consequences of memory retrieval.
Dynamic and Selective Low-Complexity Domain Interactions Revealed by Live-Cell Single-Molecule Imaging
Authors: Chong Shasha , Dugast-Darzacq Claire , Liu Zhe , Dong Peng , Dailey Gina M. , Cattoglio Claudia , Banala Sambashiva , Lavis Luke , Darzacq Xavier , Tjian Robert
Published: October 2017

Many eukaryotic transcription factors (TFs) contain intrinsically disordered low-complexity domains (LCDs) but how they perform transactivation functions remains unclear. Recent studies report that TF-LCDs can undergo hydrogel formation or liquid-liquid phase separation in vitro. Here, live-cell single-molecule imaging reveals that TF-LCDs form local high concentration interaction hubs at synthetic and endogenous genomic loci. TF-LCD hubs stabilize DNA binding, recruit RNA polymerase II (Pol II) and activate transcription. LCD-LCD interactions within hubs are highly dynamic, display selectivity with binding partners, and are differentially sensitive to disruption by hexanediols. These findings suggest that under physiological conditions, rapid reversible and multivalent LCD-LCD interactions occur between TFs and the Pol II machinery, which underpins a central mechanism for transactivation and plays a key role in gene expression and disease.
White matter haemodynamics: basic physiology and disruption in neuroinflammatory disease
Authors: Kolbe Scott. C. , Gajamange Sanuji. I. , Cleary Jon. O.S.H. , Kilpatrick Trevor. J.
Published: October 2017

The white matter is highly vascularised by the cerebral venous system. The neuroinflammatory disease multiple sclerosis is associated with infiltration of peripheral immune cells into the brain via these vessels. Understanding venous pathophysiology in multiple sclerosis is thus critical for understanding early disease aetiology. In this paper, we describe a unique blood oxygen-level dependent (BOLD) signal within the white matter using functional MRI and spatial independent components analysis, a blind signal source separation method. The signal was characterised by a narrow peak frequency band between 0.05 and 0.1 Hz. Hypercapnia (transient breath holds), known to alter venous calibre in cortex, induced transient increases in white matter BOLD that disrupted the oscillation indicative of a vasodilatory/contractile mechanism. Comparison of the white matter BOLD oscillations between age and sex matched groups of 18 multiple sclerosis and 14 healthy participants revealed a loss of power in the white matter BOLD signal in the peak frequency band (patients = 6.70±0.94 dB/Hz vs controls = 7.64±0.71 dB/Hz; p=0.006). In multiple sclerosis patients, lower power was associated with greater levels of neuroinflammatory activity (R=−0.64, p=0.006) but not neurodegenerative disease markers. Using a signal modelling technique, we assessed the anatomical distribution of white matter BOLD signal abnormalities and detected reduced power in the periventricular white matter, a region of known venous damage in multiple sclerosis patients. These results demonstrate a novel link between neuroinflammation and vascular physiological dysfunction in the cerebral white matter, and could indicate enduring loss of vascular compliance associated with imperfect repair of blood-brain barrier damage after resolution of acute neuroinflammation.
Discovering lncRNA Mediated Sponge Interactions in Breast Cancer Molecular Subtypes
Authors: Olgun Gulden , Sahin Ozgur , Tastan Oznur
Published: October 2017

Motivation

Long non-coding RNAs(lncRNAs) can indirectly regulate mRNAs expression levels by sequestering microRNAs (miRNAs), and act as competing endogenous RNAs (ceRNAs) or as sponges. Previous studies identified lncRNA-mediated sponge interactions in various cancers including the breast cancer. However, breast cancer subtypes are quite distinct in terms of their molecular profiles; therefore, ceRNAs are expected to be subtype-specific as well.

Results

To find lncRNA-mediated ceRNA interactions in breast cancer subtypes, we develop an integrative approach. We conduct partial correlation analysis and kernel independence tests on patient gene expression profiles and further refine the candidate interactions with miRNA target information. We find that although there are sponges common to multiple subtypes, there are also distinct subtype-specific interactions. Functional enrichment of mRNAs that participate in these interactions highlights distinct biological processes for different subtypes. Interestingly, some of the ceRNAs also reside in close proximity in the genome; for example, those involving HOX genes, HOTAIR, miR-196a-1 and miR-196a-2. We also discover subtype-specific sponge interactions with high prognostic potential. For instance, when grouping is based on the expression patterns of specific sponge interactions, patients differ significantly in their survival distributions. If on the other hand, patients are grouped based on the individual RNA expression profiles of the sponge participants, they do not exhibit a significant difference in survival. These results can help shed light on subtype-specific mechanisms of breast cancer, and the methodology developed herein can help uncover sponges in other diseases.
Massive Phenotypic Measurements Reveal Complex Physiological Consequences of Differential Translation Efficacies
Authors: Arkin Adam Paul , Cambray Guillaume
Published: October 2017

ABSTRACT

Control of protein biosynthesis is at the heart of resource allocation and cell adaptation to fluctuating environments. One gene’s translation often occurs at the expense of another’s, resulting in global energetic and fitness trade-offs during differential expression of various functions. Patterns of ribosome utilization—as controlled by initiation, elongation and release rates—are central to this balance. To disentangle their respective determinants and physiological impacts, we complemented measurements of protein production with highly parallelized quantifications of transcripts’ abundance and decay, ribosome loading and cellular growth rate for 244,000 precisely designed sequence variants of an otherwise standard reporter. We find highly constrained, non-monotonic relationships between measured phenotypes. We show that fitness defects derive either from protein overproduction, with efficient translation initiation and heavy ribosome flows; or from unproductive ribosome sequestration by highly structured, slowly initiated and overly stabilized transcripts. These observations demonstrate physiological impacts of key sequence features in natural and designed transcripts.
Terminal uridylyltransferases target RNA viruses as part of the innate immune system in animals
Authors: Le Pen Jérémie , Jiang Hongbing , Di Domenico Tomás , Kneuss Emma , Kosałka Joanna , Morgan Marcos , Much Christian , Rudolph Konrad L. M. , Enright Anton J. , O’Carroll Dónal , Wang David , Miska Eric A.
Published: October 2017

RNA viruses are a major threat to animals and plants. RNA interference (RNAi) and the interferon response provide innate antiviral defense against RNA viruses. Here we performed a large-scale screen using C. elegans and its natural pathogen, the Orsay virus (OrV), and identified cde-1 as important for antiviral defense. CDE-1 is a homologue of the mammalian TUT4/7 terminal uridylyltransferases; its catalytic activity is required for its antiviral function. CDE-1 uridylates the 3′ end of the OrV RNA genome and promotes its degradation, independently of the RNAi pathway. Likewise, TUT4/7 uridylate influenza A virus (IAV) mRNAs in mammalian cells. Deletion of TUT4/7 leads to increased IAV mRNA and protein levels. We have defined 3′ terminal uridylation of viral RNAs as a conserved antiviral defense mechanism.
{\bb Z}-module defects in crystals
Authors: Sirindil Abdullah , Quiquandon Marianne , Gratias Denis
Published: October 2017

An analysis is presented of the new types of defects that can appear in crystalline structures where the positions of the atoms and the unit cell belong to the same {\bb Z}-module,i.e.are irrational projections of anN> 3-dimensional (N-D) lattice Λ as in the case of quasicrystals. Beyond coherent irrationally oriented twins already discussed in a previous paper [Quiquandonet al.(2016).Acta Cryst.A72, 55–61], new two-dimensional translational defects are expected, the translation vectors of which, being projections of nodes of Λ, have irrational coordinates with respect to the unit-cell reference frame. Partial dislocations, called heremodule dislocations, are the linear defects bounding these translation faults. A specific case arises when the Burgers vectorBis the projection of a non-zero vector of Λ that is perpendicular to the physical space. This new kind of dislocation is called ascalar dislocationsince, because its Burgers vector in physical space is zero, it generates no displacement field and has no interaction with external stress fields and other dislocations.
A note on X-ray spherical wavefields in the Laue case for perfect crystals
Authors: Saka Takashi
Published: October 2017

Spherical wavefields in the Laue case are obtained when the real part of the crystal structure factor is zero or small compared with the imaginary part. The results are the same as in the conventional case where the real part is large. Through this work, it is shown that virtual wavefields on the vacuum side should be taken into account to explain the obtained results. It is also shown that, to obtain the virtual wavefields, a modification of the conventional spherical wave theory is necessary.
Qualitative exploration of psychotropic medication to manage challenging behaviour in adults with intellectual disability: views of family members
Authors: Edwards Nicole , King Julie , Watling Hanna , Hair Sara Amy
Published: October 2017

Purpose

The purpose of this paper is to produce the views of parents and siblings of adults with intellectual or developmental disability (ID/DD) around the use of psychotropic medication to manage challenging behaviour (CB) where there is no co-existing mental illness.

Design/methodology/approach

Seven family members of six adults with ID/DD were interviewed using semi-structured interviews, over the telephone or face-to-face. The interviews were transcribed, coded and thematically analysed.

Findings

This paper identified that if used appropriately, psychotropic medication to manage CB may be of benefit to some people with ID/DD; but there is a need to ensure the medication is prescribed for the benefits of people with ID/DD rather than those around them. Drawing on the knowledge of family may allow for the use of alternative strategies and the reduction of medication to manage CB. There is the need for improved communication with family members, inclusive decision making, and access to information regarding the philosophy and legislation regarding medication used to manage CB in adults with ID/DD.

Originality/value

This paper presents views of a small cohort of family members of people with ID/DD in Queensland, Australia. Findings can be used to improve approaches taken by service providers in their interactions with people with ID/DD prescribed psychotropic medication to manage CB, and their family members.
Using Photovoice as a method to engage bereaved adults with intellectual disabilities in research: listening, learning and developing good practice principles
Authors: Tajuria Gulshan , Read Sue , Priest Helena M.
Published: October 2017

Purpose

People with intellectual disabilities experiencing loss or bereavement are at risk of developing additional mental health problems, and may struggle to access suitable support. The purpose of this paper is to present the adaptations done while using Photovoice as a creative method for bereaved people with intellectual disabilities participating in a research exploring loss and support. This paper will further briefly add information on how the use of Photovoice supported the development of whole research project.

Design/methodology/approach

This paper explores the use of Photovoice as a method of research engagement for bereaved adults with intellectual disabilities. Photovoice enables participants to take and discuss photographs illustrating their loss and support experiences. The paper focusses on a preparatory Photovoice workshop with the research participants, outlining the processes and activities used to maximise involvement, promote learning and achieve shared understanding.

Findings

Preparation was the key to the effectiveness of this workshop and it recommends that appropriate adaptions are useful in Photovoice with adults with intellectual disabilities effectively. The paper outlines principles of good practice for using Photovoice in this research context, which may transfer to other similar research settings. Using Photovoice facilitated later one-to-one interviews with the participants, where their photographs were discussed together.

Originality/value

This paper illustrates the innovative use of Photovoice methodology in research involving bereaved people with intellectual disabilities. Photovoice has not previously been used with this specific population within the bereavement and loss context, so this paper adds to the developing evidence base.
Creative economy as a social technology approach
Authors: Schiray Dalia Maimon , Carvalho Cristine Clemente , Afonso Rita
Published: October 2017

Purpose

The purpose of this paper is to discuss the characteristics of creative economies in favelas and their potential in terms of social development from a comparison between the theory on creative economy and the characteristics of the initiatives mapped in the Mangueira favelas.

Design/methodology/approach

The research was based on qualitative methodology and literature review. The creative economy initiatives were mapped in the territory of Mangueira and semi-structured interviews and questionnaire of closed questions were applied with the representatives of these. The data collected were treated with the content analysis method.

Findings

The research mapped 17 initiatives associated with creative economy sectors in the Mangueira favelas in Rio de Janeiro, Brazil. The initiatives develop cultural and artistic activities that make the young people of the community aware of the history of their families, which promotes the strengthening of social ties and individual empowerment, contributing to local entrepreneurship.

Practical implications

The theory used in Brazil for the elaboration of public policies to promote the creative economy points to the presence of cultural and symbolic aspects in economic activities as resources for the generation of income. However, it is important to understand how this applies in different contexts, which may have or lack certain characteristics of human and physical capital pointed as essential by theory to creative economy promotion.

Originality/value

The results of this research go beyond the theory of creative economy and highlight characteristics of project management and impacts on social development that demonstrate how the dynamics of the creative economy in the Mangueira favelas also represent a case of social innovation using social technology tools.
Financial exposure and technology innovation investment
Authors: Quintella Vitor da Mata , Silva Jr Antônio Francisco de Almeida da , Almeida Jose Ricardo Uchoa Cavalcanti , Embiruçu Marcelo
Published: October 2017

Purpose

The purpose of this paper is to identify, measure and optimise financial risk and its effect on returns from innovation projects on an accrual basis and on a cash basis in a commodity industry.

Design/methodology/approach

A hypothetical case study, based on a real case, of a petrochemical commodity industry in Brazil was analysed with commodities pricing rules based on actual contracts. Earnings at risk (EaR) and cash flow at risk (CFaR) measures were applied, as well as a metric proposed in this paper called cash balance at risk (CBaR).

Findings

The paper demonstrates that financial risk measurement and optimisation are important issues in the decision-making process in the petrochemical industry. EaR, CFaR and CBaR measures are helpful when used alongside standard procedures of project evaluation. The findings also show that innovative technologies, in certain conditions, may act as “natural hedging”. It was found that the time delay between revenues and expenses leads to financial risk exposure to changes in prices and foreign exchange rates. Projects can use financing and hedging to boost their results.

Originality/value

An innovative project was compared with an expansion project in a petrochemical industry. A model for petrochemical commodities contract pricing was added in an analysis that included financing and hedging. The findings in this paper suggest that it is important to consider financial risk measures in project evaluation.