bluuebunny/crossref_metadata_2025 huggingface dataset:
FDG PET/MRI Findings Pointing Toward a Gayet-Wernicke Encephalopathy
Authors: Rozenblum Laura , Habert Marie-Odile , Pyatigorskaya Nadya , Roue-Jagot Carole , Kas Aurélie
Published: May 2019

We report a case of Gayet-Wernicke encephalopathy, revealed by an 18F-FDG PET/MRI performed in a patient with memory impairment. Metabolism showed no pattern of neurodegenerative disease, but a severe decrease in hippocampus and mammillary bodies (MBs). MRI images analyzed in light of PET findings revealed MB atrophy coupled with signal-intensity alterations, suggestive of a Gayet-Wernicke encephalopathy. Patient was known for alcohol use disorders, and all previous MRI scans were considered as inconclusive. Symptoms improved with correction of thiamine (vitamin B1) deficiency. This report highlights ability of hybrid PET/MRI to investigate small neuronal structures, such as the MBs involved in Gayet-Wernicke disease.
The Preventive Effect of Parotid Gland Massage on Salivary Gland Dysfunction During High-Dose Radioactive Iodine Therapy for Differentiated Thyroid Cancer
Authors: Son Seung Hyun , Lee Chang-Hee , Jung Ji-Hoon , Kim Do-Hoon , Hong Chae Moon , Jeong Ju Hye , Jeong Shin Young , Lee Sang-Woo , Lee Jaetae , Ahn Byeong-Cheol
Published: May 2019

Purpose

To evaluate the preventive effect of parotid gland (PG) massage for PG damage during the131I therapy, we prospectively investigated the serum amylase value and salivary gland scintigraphy (SGS) after131I therapy.

Materials and Methods

One hundred patients with thyroidectomized differentiated thyroid cancer who underwent high-dose131I therapy were enrolled in the clinical trial and randomized into 2 groups (PG massage group and nonmassage group). The serum amylase value was obtained before and 24 hours after131I therapy, and the SGSs were also taken just before and at 8 months after the131I therapy. Change in serum amylase value and SGS was compared between PG massage and nonmassage groups.

Results

The difference value of serum amylase was significantly lower in PG massage group than in nonmassage group (P= 0.0052). Worsening of PG function on SGS was observed in 43 (45.3%) of the 95 patients. The incidence rate of PG abnormality on F/U SGS was significantly lower in PG massage group than in nonmassage group (odds ratio, 0.3704;P= 0.0195). In the multiple regression analysis, PG massage significantly affected the abnormality on the 8-month F/U SGS (rpartial= −0.2741,P= 0.0090) after adjusting for clinical variables (age, sex, TNM stage, TSH preparation methods for the131I therapy, and131I dose).

Conclusions

PG gland massage significantly reduced the incidence rates of salivary gland dysfunction on the 8-month F/U SGS and the level of the serological marker of salivary gland destruction after131I therapy. Therefore, PG gland massage could alleviate salivary gland damage related to131I therapy.
Heterogeneity of 68Ga-PSMA PET/CT Uptake in Fibrous Dysplasia
Authors: Plouznikoff Nicolas , Garcia Camilo , Artigas Carlos , Entezari Kim , Flamen Patrick
Published: May 2019

Fibrous dysplasia is an uncommon benign bone pathology with only rare potential for malignant transformation. We describe the heterogeneous uptake of fibrous dysplasia of a whole rib on 68Ga-labeled prostate-specific membrane antigen (PSMA) PET/CT. 68Ga-PSMA binds to PSMA-expressing prostate cancer cells, but it can also bind to the neovasculature of various solid tumors, as well as to some benign lesions. 68Ga-PSMA expression in fibrous dysplasia should not automatically be equated with malignant transformation or confused with prostate cancer metastases.
Is Piezoelectric Surgery Really Harmless to Soft Tissue?
Authors: Demirbilek Nevzat , Evren Cenk
Published: May 2019

Aim:

The aim of this study was to investigate the effect of piezoelectric surgery (piezosurgery) on soft tissue in open septorhinoplasty.

Methods:

A total of 30 patients (21 females, 9 males; mean age 29.16 ± 8.17 years; range, 18–43 years) who underwent open septorhinoplasty between January 2019 and February 2019 were randomly divided into 2 groups. After the nasal dorsum was opened in all groups, 1 mm3 tissue under the skin in radix region was taken as punch biopsy. In the first group (classical group, n =  15), the cartilage hump was resected with number 15 scalpel and the bone hump with the help of a chisel. Lateral and median osteotomies were conducted using 4 mm sharp osteotomes. Rasping was performed to dorsum to correct bone deformities. Then, 1 mm3 punch biopsy was taken from under the skin tissue of the nose back near the radix. In the second group (piezo group, n = 15) hump excision, osteotomies and rasping were performed by piezoelectric surgery. Then, 1 mm3 punch biopsy was taken from the subcutaneous tissue of the nose back near the radix. Biopsies were examined histopathologically in the light microscope for edema, necrosis, and inflammation.

Results:

Of the 30 patients presented in this series, 21 were female and 9 were male. In the classical group, edema in the soft tissue was seen in 86.7% of the cases after osteotomy, while this rate was 26.7% in the piezosurgery group. The difference was statistically significant (P < 0.05). Although necrosis was not seen prior to the osteotomy in both groups, the rate of necrosis in the classical group was 13.3% and in the piezo group it was 66.7%. Necrosis was significantly different in the piezosurgery group compared with the classical osteotomy group (P < 0.05).

Conclusion:

Piezosurgery is not completely harmless to soft tissue. A statistically significant increase in subcutaneous necrosis compared with the classical group can be explained by long-term soft tissue trauma caused by piezoelectric vibrations. We think that developing necrosis may cause problems in late period, especially in patients with thin skin.
The Association of Fever and Antipyretic Medication With Outcomes in Mechanically Ventilated Patients: A Cohort Study
Authors: Evans Emily M. , Doctor Rebecca J. , Gage Brian F. , Hotchkiss Richard S. , Fuller Brian M. , Drewry Anne M.
Published: May 2019

Background:

Fever is common in mechanically ventilated patients and may be uniquely detrimental in those with lung injury because of its injurious effects on pulmonary vascular permeability and alveolar epithelium. We evaluated the association of fever and antipyretic medication with mortality in mechanically ventilated emergency department (ED) patients.

Methods:

This is a retrospective cohort study of 1,264 patients requiring mechanical ventilation initiated in the ED with subsequent admission to an intensive care unit. Maximum body temperature was recorded for the first 24 h after ED admission and categorized into four categories: <37°C, 37°C to 38.2°C, 38.3°C to 39.4°C, and ≥39.5°C. The primary outcome was 28-day mortality. We conducted a planned subgroup analysis of patients with sepsis at the time of intubation. Multivariable Cox proportional hazard ratios (HRs) were used to assess the relationship between temperature, antipyretics, and mortality.

Results:

Multivariable Cox proportional HRs demonstrated that a maximum temperature ≥39.5°C was associated with increased mortality (adjusted hazard ratio [aHR] 1.59 [95% confidence interval, CI, 1.05–2.39]). In the subgroup of patients with sepsis, a maximum temperature of 38.3°C to 39.4°C was associated with survival (aHR 0.61 [95% CI, 0.39–0.99]). There was no difference in 28-day mortality between patients who did and did not receive antipyretic medication in either the overall cohort or the septic subgroup.

Conclusion:

High fever (≥39.5°C) was associated with increased risk for mortality in mechanically ventilated patients. However, in patients with sepsis, moderate fever (38.3°C–39.4°C) was protective. Antipyretic medication was not associated with changes in outcome. This suggests that fever may have different implications in septic versus nonseptic mechanically ventilated patients.
Effect of Microvascular Invasion Risk on Early Recurrence of Hepatocellular Carcinoma After Surgery and Radiofrequency Ablation
Authors: Lee Sunyoung , Kang Tae Wook , Song Kyoung Doo , Lee Min Woo , Rhim Hyunchul , Lim Hyo Keun , Kim So Yeon , Sinn Dong Hyun , Kim Jong Man , Kim Kyunga , Ha Sang Yun
Published: May 2019

Objective:

We compared surgical resection (SR) and radiofrequency ablation (RFA) as first-line treatment in patients with hepatocellular carcinoma (HCC) based on the risk of microvascular invasion (MVI).

Background:

The best curative treatment modality between SR and RFA in patients with HCC with MVI remains unclear.

Methods:

Data from 2 academic cancer center-based cohorts of patients with a single, small (≤3 cm) HCC who underwent SR were used to derive (n = 276) and validate (n = 101) prediction models for MVI using clinical and imaging variables. The MVI prediction model was developed using multivariable logistic regression analysis and externally validated. Early recurrence (<2 years) based on risk stratification between SR (n = 276) and RFA (n = 240) was evaluated via propensity score matching.

Results:

In the multivariable analysis, alpha-fetoprotein (≥15 ng/mL), protein induced by vitamin K absence-II (≥48 mAU/mL), arterial peritumoral enhancement, and hepatobiliary peritumoral hypointensity on magnetic resonance imaging were associated with MVI. Incorporating these factors, the area under the receiver operating characteristic curve of the predictive model was 0.87 (95% confidence interval: 0.82–0.92) and 0.82 (95% confidence interval: 0.74–0.90) in the derivation and validation cohorts, respectively. SR was associated with a lower rate of early recurrence than RFA based on the risk of MVI after propensity score matching (P < 0.05).

Conclusions:

Our model predicted the risk of MVI in patients with a small (≤ 3 cm) HCC with high accuracy. Patients with MVI who had undergone RFA were more vulnerable to recurrence than those who had undergone SR.
Prevalence and Risk Factors for Chronic Abdominal Pain After Roux-en-Y Gastric Bypass Surgery
Authors: Gormsen Johanne , Burcharth Jakob , Gögenur Ismail , Helgstrand Frederik
Published: May 2019

Objective:

To investigate the prevalence and risk factors for chronic abdominal pain after Roux-en-Y gastric bypass (RYGB) surgery.

Summary Background Data:

Abdominal pain is a frequent postoperative complication after RYGB surgery. Even if there have been defined several long-term complications, the literature regarding patients with unexplained chronic abdominal pain is sparse.

Methods:

A single-center register-based cohort study with inclusion of all patients who underwent RYGB surgery between 2010 and 2015. Data from multiple registries, medical records, and a questionnaire were used. Patients with chronic abdominal pain were defined as those using strong analgesics, diagnosed with chronic pain, or referred to a specialized pain clinic. Patients with severe self-reported abdominal pain were defined as those reporting abdominal pain more than 2 times weekly within the last month.

Results:

A total of 787 patients were followed for a median of 63 months. The prevalence of postoperative chronic abdominal pain was 11% and the prevalence of severe self-reported abdominal pain was 21%. Preoperative use of strong analgesics was a risk factor for chronic abdominal pain (OR, 2.26; 95% CI, 1.59–3.23) and severe self-reported abdominal pain (OR 2.82, 95% CI 1.64–4.84). Further risk factors for severe self-reported pain were unemployment or retirement (OR 1.80, 95% CI 1.09–2.93), postoperative complications (OR 2.75, 95% CI 1.44–5.22), and smoking (OR 1.80, 95% CI 1.09–2.96).

Conclusions:

One in 10 patients undergoing RYGB surgery developed chronic abdominal pain requiring strong analgesics, and one in five suffered from severe abdominal pain. Risk factors were preoperative use of strong analgesics, unemployment, postoperative complications, and smoking.
Randomized Controlled Phase 2a Study of RPh201 in Previous Nonarteritic Anterior Ischemic Optic Neuropathy
Authors: Rath Eitan Z. , Hazan Zadik , Adamsky Konstantin , Solomon Arieh , Segal Zvi I. , Levin Leonard A.
Published: May 2019

Background:

No proven treatment exists for nonarteritic anterior ischemic optic neuropathy (NAION), either in the acute or late phase.

Objective:

To assess safety and changes in visual function and structure after RPh201/placebo treatment in participants with previous NAION.

Design and Setting:

Phase 2a, single-site, prospective, randomized, placebo-controlled, double-masked trial (registration NCT02045212).

Main Outcomes Measures:

Early Treatment Diabetic Retinopathy Study best-corrected visual acuity (BCVA), visual fields, retinal nerve fiber layer, and visual evoked potential at weeks 13, 26, and after a 13-week wash-out (“off-drug”) period; and safety.

Study Population:

Twenty-two participants aged 18 years or older with previous NAION.

Intervention(s):

RPh201 (20 mg) or placebo (cottonseed oil vehicle) administered subcutaneously twice weekly at the study site.

Results:

Thirteen men and 9 women were randomized, of which 20 completed all visits. The mean (±SD) age was 61.0 ± 7.6 years. In a post hoc analysis, after 26 weeks of treatment, BCVA improved by ≥15 letters in 4/11 (36.4%) eyes with RPh201, compared to 1/8 (12.5%) eyes with placebo (P = 0.24). Overall, 7/11 (63.6%) of participants on RPh201 showed some improvement in BCVA, compared with 3/8 (37.5%) on placebo (P = 0.26). Improvement in BCVA from a calculated baseline was 14.8 ± 15.8 letters for RPh201 and 6.6 ± 15.3 for placebo (P = 0.27). Of the 154 adverse effects (AEs), 52 were considered related to the study procedures/treatment. Across the study and 1,017 injections, the most frequently reported AE was injection site pain (23 events in 5 participants). There were no clinically significant changes in vital signs or laboratory values.

Conclusions:

This Phase 2a was designed to assess safety, feasibility, and explore potential efficacy signals in treating previous NAION with RPh201. No safety concerns were raised. The results support a larger trial in patients with previous NAION.
Continuous EEG Monitoring Predicts a Clinically Meaningful Recovery Among Adult Inpatients
Authors: Selioutski Olga , Roberts Debra , Hamilton Ross , Ghosh Hia , Nickels Jean , Konig Toro Francesca , Kruppenbacher Matthew , Auinger Peggy , Kaplan Peter W. , Birbeck Gretchen L.
Published: May 2019

Purpose:

Continuous EEG (cEEG) monitoring is primarily used for diagnosing seizures and status epilepticus, and for prognostication after cardiorespiratory arrest. The purpose of this study was to investigate whether cEEG could predict survival and meaningful recovery.

Methods:

The authors reviewed inpatient cEEG reports obtained between January 2013 and November 2015 and recorded demographics, preadmission modified Rankin Scale, history of preexisting epilepsy, Glasgow Coma Scale for those admitted to the intensive care unit, and EEG data (posterior dominant rhythm, reactivity, epileptiform discharges, seizures, and status epilepticus). Associations between clinical outcomes (death vs. survival or clinically meaningful recovery [inpatient rehabilitation, home-based rehabilitation, or home] vs. other [death, skilled nursing facility]) and cEEG findings were assessed with logistic regression models. P < 0.05 was considered significant.

Results:

For 218 cEEG reports (197 intensive care unit admits), the presence of at least a unilateral posterior dominant rhythm was associated with survival (odds ratio for death, 0.38; 95% confidence interval, 0.19–0.77; P = 0.01) and with a clinically meaningful outcome (odds ratio, 3.26; 95% confidence interval, 1.79–5.93; P < 0.001); posterior dominant rhythm remained significant after adjusting for preadmission disability. Those with preexisting epilepsy had better odds of a meaningful recovery (odds ratio, 3.31; 95% CI, 1.34–8.17; P = 0.001). Treated seizures and status epilepticus were not associated with a worse mortality (P = 0.6) or disposition (P = 0.6). High Glasgow Coma Scale (≥12) at intensive care unit admission was associated with a clinically meaningful recovery (odds ratio, 16.40; 95% confidence interval, 1.58–170.19; P = 0.02).

Conclusions:

Continuous EEG findings can be used to prognosticate survival and functional recovery, and provide guidance in establishing goals of care.
Updated Database and Evolutionary Dynamics of U12-Type Introns
Authors: Moyer Devlin C. , Larue Graham E. , Hershberger Courtney E. , Roy Scott W. , Padgett Richard A.
Published: May 2019

During nuclear maturation of most eukaryotic pre-messenger RNAs and long non-coding RNAs, introns are removed through the process of RNA splicing. Different classes of introns are excised by the U2-type or the U12-type spliceosomes, large complexes of small nuclear ribonucleoprotein particles and associated proteins. We created intronIC, a program for assigning intron class to all introns in a given genome, and used it on 24 eukaryotic genomes to create the Intron Annotation and Orthology Database (IAOD). We then used the data in the IAOD to revisit several hypotheses concerning the evolution of the two classes of spliceosomal introns, finding support for the class conversion model explaining the low abundance of U12-type introns in modern genomes.
Multi-Scale, Patient-Specific Computational Flow Dynamics Models Predict Formation of Neointimal Hyperplasia in Saphenous Vein Grafts
Authors: Donadoni Francesca , Pichardo-Almarza Cesar , Homer-Vanniasinkam Shervanthi , Dardik Alan , Díaz-Zuccarini Vanessa
Published: May 2019

Bypass occlusion due to neointimal hyperplasia (NIH) is among the major causes of peripheral graft failure. Its link to abnormal hemodynamics in the graft is complex, and isolated use of hemodynamic markers insufficient to fully capture its progression. Here, a computational model of NIH growth is presented, establishing a link between computational fluid dynamics (CFD) simulations of flow in the lumen, with a biochemical model representing NIH growth mechanisms inside the vessel wall. For all 3 patients analyzed, NIH at proximal and distal anastomoses was simulated by the model, with values of stenosis comparable to the computed tomography (CT) scans.
Non-production vegetation has a positive effect on ecological processes in agroecosystems
Authors: Case Bradley S. , Pannell Jennifer L. , Stanley Margaret C. , Norton David A. , Brugman Anoek , Funaki Matt , Mathieu Chloé , Songling Cao , Suryaningrum Febyana , Buckley Hannah L.
Published: May 2019

An ever-expanding human population, ongoing global climatic changes, and the spread of intensive farming practices is putting increasing pressure on agroecosystems and the inherent biodiversity they contain. Non-production vegetation elements, such as woody patches, riparian margins, and inter-crop and restoration plantings, are vital for conserving biodiversity in agroecosystems and are therefore considered key to sustaining the biotic and abiotic processes underpinning sustainable and resilient agroecosystems. Despite this critical role, there is a surprising lack of synthesis of which types of non-production vegetation elements drive and/or support ecological processes and the mechanisms by which this occurs. Using a systematic, quantitative literature review of 342 articles, we asked: what are the effects of non-production vegetation elements on agroecosystem processes and how are these processes measured within global agroecosystems? Our literature search focussed on the effects of non-production vegetation related to faunal, weed, disease, and abiotic processes. The majority (61%) of studies showed positive effects on ecological processes: non-production vegetation increased the presence, level or rate of the studied process. However, rather than directly measuring ecosystem processes, 83% of studies inferred processes using proxies for ecosystem function, such as biodiversity and soil physicochemical properties. Studies that directly measured non-production vegetation effects focussed on a limited number of vegetation effects including comparisons of vegetation types, farm-scale configuration, and proximity to vegetation. Moreover, studies directly measuring ecosystem processes were similarly limited, dominated by invertebrate biocontrol, predator and natural enemy spillover, animal movement, and ecosystem cycling. We identify research gaps and present a pathway for future research in understanding the ecosystem components and processes that build resilient, sustainable agroecosystems.
Corticothalamic gating of population auditory thalamocortical transmission in mouse
Authors: Ibrahim Baher A. , Murphy Caitlin , Muscioni Guido , Taheri Aynaz , Yudintsev Georgiy , Kenyon Robert V. , Berger-Wolf Tanya , Banks Matthew I. , Llano Daniel A.
Published: May 2019

Since the discovery of the receptive field, scientists have tracked receptive field structure to gain insights about mechanisms of sensory processing. At the level of the thalamus and cortex, this linear filter approach has been challenged by findings that populations of cortical neurons respond in a stereotyped fashion to sensory stimuli. Here, we elucidate a possible mechanism by which gating of cortical representations occurs. All-or-none population responses (here called “ON” and “OFF” responses) were observed in vivo and in vitro in the mouse auditory cortex at near-threshold acoustic or electrical stimulation. ON-responses were associated with previously-described UP states in the auditory cortex. OFF-responses in the cortex were only eliminated by blocking GABAergic inhibition in the thalamus. Opto- and chemogenetic silencing of NTSR-positive corticothalamic layer 6 (CTL6) neurons as well as the pharmacological blocking of the thalamic reticular nucleus (TRN) retrieved the missing cortical responses, suggesting that the corticothalamic feedback inhibition via TRN controls the gating of thalamocortical activity. Moreover, the oscillation of the pre-stimulus activity of corticothalamic cells predicted the cortical ON vs. OFF responses, suggesting that underlying cortical oscillation controls thalamocortical gating. These data suggest that the thalamus may recruit cortical ensembles rather than linearly encoding ascending stimuli and that corticothalamic projections play a key role in selecting cortical ensembles for activation.
Partial migration in a subtropical wading bird in the Southeastern U.S.
Authors: Picardi Simona , Frederick Peter C. , Borkhataria Rena R. , Basille Mathieu
Published: May 2019

The function of migration is to allow exploitation of resources whose availability is heterogeneous in space and time. Much effort has been historically directed to studying migration as a response to seasonal, predictable fluctuations in resource availability in temperate species. A deeper understanding of how different migration patterns emerge in response to different patterns of resource variation requires focusing on species inhabiting less predictable environments, especially in tropical and subtropical areas. We provide the first individual-based, quantitative description of migratory patterns in a subtropical wading bird in the Southeastern U.S., the wood stork (Mycteria americana). Using GPS tracking data for 64 individuals tracked between 2004 and 2017, we classified migratory behavior at the individual-year level using information theory-based model selection on non-linear models of net squared displacement. We found that the wood stork population is partially migratory, with 59% of individuals seasonally commuting between winter ranges in Florida and summer ranges elsewhere in the population range (migrants), and 28% remaining in a single area in Florida year-round (residents). Additionally, 13% of storks act as facultative migrants, migrating in some years but not in others. Comparing the distribution of residents and migrants suggests that different migratory strategies might be associated with the use of different or differently distributed resources, possibly including food supplementation from human activities. The existence of facultative migrants shows the potential for plastic change of migratory patterns. Partial migration in wood storks may be an adaptation to high heterogeneity and unpredictability of food resources. We suggest that future research should focus on wading birds as model species for the study of partial migration as an adaptation to heterogeneous and unpredictable environments, by comparing populations of the same species across different wetland systems and sympatric populations of species that differ in their resource acquisition mechanisms.
Screening human embryos for polygenic traits has limited utility
Authors: Karavani Ehud , Zuk Or , Zeevi Danny , Atzmon Gil , Barzilai Nir , Stefanis Nikos C. , Hatzimanolis Alex , Smyrnis Nikolaos , Avramopoulos Dimitrios , Kruglyak Leonid , Lam Max , Lencz Todd , Carmi Shai
Published: May 2019

Genome-wide association studies have led to the development of polygenic score (PS) predictors that explain increasing proportions of the variance in human complex traits. In parallel, progress in preimplantation genetic testing now allows genome-wide genotyping of embryos generated viain vitrofertilization (IVF). Jointly, these developments suggest the possibility of screening embryos for polygenic traits such as height or cognitive function. There are clear ethical, legal, and societal concerns regarding such a procedure, but these cannot be properly discussed in the absence of data on the expected outcomes of screening. Here, we use theory, simulations, and real data to evaluate the potential gain of PS-based embryo selection, defined as the expected difference in trait value between the top-scoring embryo and an average, unselected embryo. We observe that the gain increases very slowly with the number of embryos, but more rapidly with increased variance explained by the PS. Given currently available polygenic predictors and typical IVF yields, the average gain due to selection would be ≈2.5cm if selecting for height, and ≈2.5 IQ (intelligence quotient) points if selecting for cognitive function. These mean values are accompanied by wide confidence intervals; in real data drawn from nuclear families with up to 20 offspring each, we observe that the offspring with the highest PS for height was the tallest only in 25% of the families. We discuss prospects and limitations of PS-based embryo selection for the foreseeable future.
Monte Carlo Simulation of Diffusion MRI in geometries constructed from two-photon microscopy of human cortical grey matter
Authors: Gilani Nima , Hildebrand Sven , Schueth Anna , Roebroeck Alard
Published: May 2019

Purpose

Neurodegenerative diseases such as Alzheimer’s disease cause changes and disruption to cortical microstructure and architecture. Diffusion MRI (dMRI) could potentially be sensitive to such changes. There is a growing interest in modeling of human cortical areas using a combination of quantitative MRI and 3D microscopy. The purpose of this study was to quantitatively characterize the cytoarchitecture of human cortical tissue from 3D fluorescence microscopy to simulate diffusion MRI (dMRI) signal in the cortex to better understand its diffusion signal characteristics.

Methods

Diffusion of water molecules and dMRI signal were simulated by an indirect geometry based method and a direct voxel based method in microstructural details extracted from microscopy of cortex. Additionally, residence times of diffusing spins inside voxel volumes were considered to set effective resolution limits. Mean diffusivity (MD) and kurtosis (MK) were calculated for variable cell and neurite densities, sizes and diffusion times under realistic values for permeability and free diffusion.

Results

Both simulation methods could efficiently and accurately simulate dMRI signals with fractional anisotropy, diffusion coefficient and kurtosis in agreement with previous reports. Simulated MD and MK showed changes with increasing diffusion times specific to cortical cell density and sizes, with MK showing the highest sensitivity. Intra-voxel residence times with increasing diffusion times showed that the effective dMRI resolution approaches the thickness of cortical layers.

Conclusions

Monte Carlo simulations based on 3D microscopy data enable estimating changes in MD and MK over diffusion times and are sensitive to cortical cytoarchitecture and its possible changes in neurodegenerative disease. When considering layer-specific cortical dMRI, effective resolution due to residence times is an important concern.
Molecular signatures of selection associated with host-plant differences in Pieris butterflies
Authors: Okamura Yu , Sato Ai , Tsuzuki Natsumi , Murakami Masashi , Heidel-Fischer Hanna , Vogel Heiko
Published: May 2019

Adaptive traits that enable organisms to conquer novel niches and experience subsequent diversification are ecologically and evolutionarily important. The larvae of Pieris butterflies express nitrile-specifier proteins (NSPs), a key innovation for overcoming the glucosinolate (GLS)-myrosinase-based defense system of their Brassicales host-plants. NSPs are a member of the NSP-like gene family, which includes the major allergen (MA) protein, a paralog of NSP with a GLS-disarming function, and a single domain major allergen (SDMA) protein, whose function is unknown. The arms-race between a highly variable host-plant defense system and members of the NSP-like gene family is suggested to mediate diversification in both Pierid butterflies and Brassicales plants. Here, we combined feeding experiments using 25 Brassicaceae plants and five Pieris species with larval transcriptome data to investigate the evolutionary forces acting on NSP-like gene family members associated with patterns of host-plant usage. Although we observed significantly elevated nonsynonymous to synonymous substitution ratios in NSPs, no such pattern was observed in MAs or SDMAs. Furthermore, we found a signature of positive selection of NSP at a phylogenetic branch which reflects different host-plant preferences. Our data indicate that NSPs have evolved in response to shifting preferences for host plants among five Pieris butterflies, whereas MAs and SDMAs appear to have more conserved functions. Our results show that the evolution and functional differentiation of key genes used in host-plant adaptation play a crucial role in the chemical arms-race between Pieris butterflies and their Brassicales host-plants.
A genome-wide analysis of DNA methylation identifies a novel association signal for Lp(a) concentrations in theLPApromoter
Authors: Coassin Stefan , Hermann-Kleiter Natascha , Haun Margot , Wahl Simone , Wilson Rory , Paulweber Bernhard , Kunze Sonja , Meitinger Thomas , Strauch Konstantin , Peters Annette , Waldenberger Melanie , Kronenberg Florian , Lamina Claudia
Published: May 2019

Lipoprotein(a) [Lp(a)] is a major cardiovascular risk factor, which is largely genetically determined by one major gene locus, theLPAgene. Many aspects of the transcriptional regulation ofLPAare poorly understood and the role of epigenetics has not been addressed yet. Therefore, we conducted an epigenome-wide analysis of DNA methylation on Lp(a) levels in two population-based studies (total n=2208). We identified a CpG site in theLPApromoter which was significantly associated with Lp(a) concentrations. Surprisingly, the identified CpG site was found to overlap the SNP rs76735376. We genotyped this SNP de-novo in three studies (total n=7512). The minor allele of rs76735376 (1.1% minor allele frequency) was associated with increased Lp(a) values (p=1.01e-59) and explained 3.5% of the variation of Lp(a). Statistical mediation analysis showed that the effect on Lp(a) is rather originating from the base change itself and is not mediated by DNA methylation levels. This finding is supported by eQTL data from 153 liver tissue samples from the GTEx project, which shows a significant association of the rs76735376 minor allele with increasedLPAexpression. In summary, our data supports a functional role of rs76735376 in the regulation ofLPAexpression.
2D or 3D? How in vitro cell motility is conserved across dimensions, and predicts in vivo invasion
Authors: Galarza Sualyneth , Kim Hyuna , Atay Naciye , Peyton Shelly R , Munson Jennifer M
Published: May 2019

Cell motility is a critical aspect of wound healing, the immune response, and is deregulated in cancer. Current limitations in imaging tools make it difficult to study cell migration in vivo. To overcome this, and to identify drivers from the microenvironment that regulate cell migration, bioengineers have developed 2D and 3D tissue model systems in which to study cell motility in vitro, with the aim of mimicking the environments in which cells move in vivo. However, there has been no systematic study to explicitly relate and compare cell motility measurements between these geometries/systems. Here, we provide such analysis on our own data, as well as across data in existing literature to understand whether, and which, in vitro models are predictive of in vivo cell motility. To our surprise, many metrics of cell movement on 2D surfaces significantly and positively correlate with cell migration in 3D environments, and cell invasion in 3D is negatively correlated with glioblastoma invasion in vivo. Finally, to best compare across complex model systems, in vivo data, and data from different labs, we suggest that groups report an effect size, a statistical tool that is most translatable across experiments and labs, when conducting experiments that affect cellular motility.
PureseqTM: efficient and accurate prediction of transmembrane topology from amino acid sequence only
Authors: Wang Qing , Ni Chong-ming , Li Zhen , Li Xiu-feng , Han Ren-min , Zhao Feng , Xu Jinbo , Gao Xin , Wang Sheng
Published: May 2019

Motivation

Rapid and accurate identification of transmembrane (TM) topology is well suited for the annotation of the entire membrane proteome. It is the initial step of predicting the structure and function of membrane proteins. However, existing methods that utilize only amino acid sequence information suffer from low prediction accuracy, whereas methods that exploit sequence profile or consensus need too much computational time.

Method

Here we propose a deep learning framework DeepCNF that predicts TM topology from amino acid sequence only. Compared to previous sequence-based approaches that use hidden Markov models or dynamic Bayesian networks, DeepCNF is able to incorporate much more contextual information by a hierarchical deep neural network, while simultaneously modeling the interdependency between adjacent topology labels.

Result

Experimental results show that PureseqTM not only outperforms existing sequence-based methods, but also reaches or even surpasses the profile/consensus methods. On the 39 newly released membrane proteins, our approach successfully identifies the correct TM segments and boundaries for at least 3 cases while all existing methods fail to do so. When applied to the entire human proteome, our method can identify the incorrect annotations of TM regions by UniProt and discover the membrane-related proteins that are not manually curated as membrane proteins.

Availability

http://pureseqtm.predmp.com/
Patterns of putative gene loss suggest rampant developmental system drift in nematodes
Authors: Woodruff Gavin C.
Published: May 2019

Gene loss often contributes to the evolution of adaptive traits. Conversely, null mutations frequently reveal no obvious phenotypic consequences. How pervasive is gene loss, what kinds of genes are dispensable, and what are the consequences of gene loss? The nematodeCaenorhabditis eleganshas long been at the forefront of genetic research, yet only recently have genomic resources become available to situate this species in its comparative phylogenetic and evolutionary context. Here, patterns of gene loss withinCaenorhabditisare evaluated using 28 nematode genomes (most of them sequenced only in the past few years). Orthologous genes detected in every species except one were defined as being lost within that species. Putative functional roles of lost genes were determined using phenotypic information fromC. elegansWormBase ontology terms as well as using existingC. eleganstranscriptomic datasets. All species have lost multiple genes in a species-specific manner, with a genus-wide average of several dozen genes per species. Counterintuitively, nearly all species have lost genes that perform essential functions inC. elegans(an average of one third of the genes lost within a species). Retained genes reveal no differences from lost genes inC. eleganstranscriptional abundance across all developmental stages when considering all 28Caenorhabitisgenomes. However, when considering only genomes in the subgenericElegansgroup, lost genes tend to have lower expression than retained genes. Taken together, these results suggest that the genetics of developmental processes are evolving rapidly despite a highly conserved adult morphology and cell lineage in this group, a phenomenon known as developmental system drift. These patterns highlight the importance of the comparative approach in interpreting findings in model systems genetics.
Quantitative evaluation of a high resolution lipidomics platform
Authors: Liu Juan , Liu Xiaojing , Xiao Zhengtao , Locasale Jason W.
Published: May 2019

Given the general importance of lipids in health and disease, there is a need for efficient technology that broadly profiles and quantitates the lipid composition of complex mixtures. In this study, we developed and quantitatively evaluated a platform that simultaneously profiles both lipids and polar metabolites from the same sample. This method was achieved by using a methyl tert-butyl ether (MTBE) extraction and employing two liquid chromatography methods coupled with high resolution mass spectrometry (LC-HRMS). This workflow enabled detection and semi-quantitation of over 300 polar metabolites as well as over 300 lipids with comprehensive coverage of diverse chemical classes. Using cultured mammalian cells as an example, we report the quantitative properties of the platform including the sensitivity and linear range. The lipidomics strategy was further applied to characterize changes to lipid metabolism upon treatment with metformin to human ovarian cancer cells. Of the 256 detected lipids, 99 lipids (39%) significantly increased, 11 lipids (4%) were significantly reduced and 146 lipids (57%) remain unchanged in metformin-treated cells. Stable isotope tracing of carbon into lipids using [13C6]-glucose further measured the contribution of de novo fatty acid synthesis to the total fatty acid pool. In summary, the platform enabled the semi-quantitative assessment of hundreds of lipid species and associated carbon incorporation from glucose in a high throughput manner.
Sex classification by resting state brain connectivity
Authors: Weis Susanne , Patil Kaustubh , Hoffstaedter Felix , Nostro Alessandra , Yeo B.T. Thomas , Eickhoff Simon B.
Published: May 2019

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A large amount of brain imaging research has focused on group studies delineating differences between males and females with respect to both cognitive performance as well as structural and functional brain organization. To supplement existing findings, the present study employed a machine learning approach to assess how accurately participants’ sex can be classified based on spatially specific resting state (RS) brain-connectivity, using two samples from the Human Connectome Project (n1 = 434, n2 = 310) and one fully independent sample from the 1000BRAINS study (n=941). The classifier, which was trained on one sample and tested on the other two, was able to reliably classify sex, both within sample and across independent samples, differing both with respect to imaging parameters and sample characteristics. Brain regions displaying highest sex classification accuracies were mainly located along the cingulate cortex, medial and lateral frontal cortex, temporo-parietal regions, insula and precuneus. These areas were stable across samples and match well with previously described sex differences in functional brain organization. While our data show a clear link between sex and regionally specific brain connectivity, they do not support a clear-cut dimorphism in functional brain organization that is driven by sex alone.
Characterisation of gastrointestinal helminths and their impact in commercial small-scale chicken flocks in the Mekong Delta of Vietnam
Authors: Van Nguyen T.B. , Cuong Nguyen V , Yen Nguyen T. Phuong , Nhi Nguyen T.H. , Kiet Bach Tuan , Hoang Nguyen V. , Hien Vo B. , Thwaites Guy , Carrique-Mas Juan J. , Ribas Alexis
Published: May 2019

Commercial small-scale chicken farms using all-in-all-out production but operating with low standards of hygiene/biosecurity are increasingly common in Vietnam. These conditions facilitate transmission of gastrointestinal helminths. However there are no published data on these parasites in these systems. The aims were: (1) to determine the prevalence/burden of gastrointestinal helminths in small-scale commercial flocks in commercial small-scale flocks in the Mekong Delta region; and (2) to investigate the association between worm burdens and birds’ weight and disease status. Randomly selected chickens (n=120) (‘normal’ flocks) were investigated at the end of their production cycle (∼18 weeks), as well as 90 chickens with signs of respiratory and/or severe disease. The gastrointestinal tract of chickens was dissected and all visible helminths were identified. 54.2% and 54.4% healthy and diseased chickens contained helminths. Diseased, colonized chickens harboured a higher mass of helminth worms (3.8 ±SD 8.6g) than colonized, healthy chickens (1.9 ±6.3g). Eight species were identified, three nematodes (Ascaridia galli, Cheilospirura hamulosa and Heterakis gallinarum), four cestodes (Hymenolepis, Raillietina cesticillus, Raillietina echinobothrida, Raillietina tetragona,) and one trematode (Echinostomatidae). Heterakis gallinarum was the most prevalent helminth (43.3% and 42.2% in healthy and sick chickens, respectively), followed by A. galli (26.7% and 41.1%). Colonized chickens weighed 101.5g less than non-colonized birds. Colonisation was significantly higher during the rainy months (May-November) for both H. gallinarum and A. galli. Anthelminthic usage was not associated with reduced helminth burdens. We recommend upgrading cleaning and disinfection and limiting access to ranging areas to control helminth infections in small-scale commercial chicken flocks.
Investigating Fibroblast-Induced Collagen Gel Contraction Using a Dynamic Microscale Platform
Authors: Zhang Tianzi , Day John H. , Su Xiaojing , Guadarrama Arturo G. , Sandbo Nathan K. , Esnault Stephane , Denlinger Loren C. , Berthier Erwin , Theberge Ashleigh B.
Published: May 2019

Mechanical forces have long been recognized as fundamental drivers in biological processes, such as embryogenesis, tissue formation and disease regulation. The collagen gel contraction (CGC) assay has served as a classic tool in the field of mechanobiology to study cell-induced contraction of extracellular matrix (ECM), which plays an important role in inflammation and wound healing. In a conventional CGC assay, cell-laden collagen is loaded into a cell culture vessel (typically a well plate) and forms a disk-shaped gel adhering to the bottom of the vessel. The decrement in diameter or surface area of the gel is used as a parameter to quantify the degree of cell contractility. In this study, we developed a microscale CGC assay with an engineered well plate insert that uses surface tension forces to load and manipulate small volumes (14 µL) of cell-laden collagen. The system is easily operated with two pipetting steps and the microscale device moves dynamically as a result of cellular forces. We used a straightforward one-dimensional measurement as the gel contraction readout. We adapted a conventional lung fibroblast CGC assay to demonstrate the functionality of the device, observing significantly more gel contraction when human lung fibroblasts were cultured in serum-containing media versus serum-free media (p≤0.01). We further cocultured eosinophils and fibroblasts in the system, two important cellular components that lead to fibrosis in asthma, and observed that soluble factors from eosinophils significantly increase fibroblast-mediated gel contraction (p≤0.01). Our microscale CGC device provides a new method for studying downstream ECM effects of intercellular cross talk using 7-35 fold less cell-laden gel than traditional CGC assays.
Efficient small-world and scale-free functional brain networks at rest using k-nearest neighbors thresholding
Authors: Forlim Caroline Garcia , Haghiri Siavash , Düzel Sandra , Kühn Simone
Published: May 2019

In recent years, there has been a massive effort to analyze the topological properties of brain networks. Yet, one of the challenging questions in the field is how to construct brain networks based on the connectivity values derived from neuroimaging methods. From a theoretical point of view, it is plausible that the brain would have evolved to minimize energetic costs of information processing, and therefore, maximizes efficiency as well as to redirect its function in an adaptive fashion, that is, resilience. A brain network with such features, when characterized using graph analysis, would present small-world and scale-free properties.

In this paper, we focused on how the brain network is constructed by introducing and testing an alternative method: k-nearest neighbor (kNN). In addition, we compared the kNN method with one of the most common methods in neuroscience: namely the density threshold. We performed our analyses on functional connectivity matrices derived from resting state fMRI of a big imaging cohort (N=434) of young and older healthy participants. The topology of networks was characterized by the graph measures degree, characteristic path length, clustering coefficient and small world. In addition, we verified whether kNN produces scale-free networks. We showed that networks built by kNN presented advantages over traditional thresholding methods, namely greater values for small-world (linked to efficiency of networks) than those derived by means of density thresholds and moreover, it presented also scale-free properties (linked to the resilience of networks), where density threshold did not. A brain network with such properties would have advantages in terms of efficiency, rapid adaptive reconfiguration and resilience, features of brain networks that are relevant for plasticity and cognition as well as neurological diseases as stroke and dementia.

Highlights

A novel thresholding method for brain networks based on k-nearest neighbors (kNN)

kNN applied on resting state fMRI from a big cohort of healthy subjects BASE-II

kNN built networks present greater small world properties than density threshold

kNN built networks present scale-free properties whereas density threshold did not