bluuebunny/crossref_metadata_2025 huggingface dataset:
Emulsified Fat Grafting Accelerates Tissue Expansion
Authors: An Ruobing , Li Shengli , Sheng Lingling , Cao Weigang
Published: December 2019

Introduction

Tissue expansion has been applied in tissue repair and reconstruction of large soft tissue defects. Stromal vascular fraction (SVF) transplantation is a promising treatment in raising expansion efficiency. However, the clinical utilization of SVF is limited because of its conventional collagenase-based production. The aim of this study was to evaluate the effect of emulsified fat (EF), SVF obtained by using mechanical method, on accelerating tissue expansion.

Materials and Methods

The microstructure of EF fragments and the proportion of mesenchymal stem cells (MSCs; CD45−/CD34+) in EF were detected. Wistar rats were divided into the following 3 groups randomly: the 1-mL EF group, the 0.5-mL EF group, and the control group. The tissue expansion was carried out twice a week to maintain the capsule pressure at 60 mm Hg. After 4 weeks, inflation volume and histological changes, which includes collagen content, cell proliferation, and capillary density, were observed to evaluate the effect of EF on tissue expansion.

Results

Mechanical emulsification effectively destroyed the mature adipocytes in adipose tissue. The proportion of MSCs population in the EF fragments was 12.40 ± 0.86%. After expansion, the inflation volume and the levels of collagen deposition, cell proliferation, and capillary density of the expanded tissue in the 1-mL EF group were significantly higher than that in the 0.5-mL EF group and the control group (P < 0.05). However, all these regenerative indicators in the 0.5-mL EF group showed no statistical difference from the control group (P > 0.05). The thickness of epidermal and dermal layers showed no significant difference among the 3 groups (P > 0.05).

Conclusions

Our findings suggested that EF grafting can be used as a new alternative to increase tissue expansion efficiency.
The Accessory Parotid Gland and its Clinical Significance
Authors: Rosa Mateusz A. , Łazarz Dominik P. , Pękala Jakub R. , Skinningsrud Bendik , Lauritzen Sigurd S. , Solewski Bernard , Pękala Przemysław A. , Walocha Jerzy A. , Tomaszewski Krzysztof A.
Published: December 2019

Purpose:

The accessory parotid gland is a collection of salivary tissue separate from the main parotid gland. When present, it may complicate parotidectomies, promote parotitis, and serve as a potential site for benign and malignant lesions to arise. The aim of this study was to provide a comprehensive and current overview of the anatomy of the accessory parotid gland, as there is a wide discrepancy in the literature regarding its prevalence.

Materials and Methods:

The authors conducted a search in PubMed, Embase, ScienceDirect, Web of Science, SciELO, BIOSIS, Current Content Connect, Korean Journal Database, and Russian Citation Index to identify all studies which reported relevant data on the accessory, with no date or language restrictions applied. Data on prevalence, side of occurrence, and sex dimorphism of the accessory parotid gland were extracted and pooled into a meta-analysis.

Results:

A total of 13 articles (n = 3115 subjects) were included in the study. The results revealed that the overall pooled prevalence of an accessory parotid gland was 32.1% (95% confidence interval: 21.2–44.0). It was more prevalent in cadaveric studies (35.8%) than in computed tomography studies (21.5%), had a higher prevalence in Asia (33.8%) as compared to North America (23.5%), and when present, it was most often found as an unilateral structure (77.8%).

Conclusions:

With respect to the findings presented, the accessory parotid gland may be considered an anatomical variation likely to encounter in the population. More anatomical studies on the structure and its prevalence are needed, in all regions of the world, to provide a representative global overview.
Seizures in Patients With Metastatic Brain Tumors: Prevalence, Clinical Characteristics, and Features on EEG
Authors: Ajinkya Shaun , Fox Jonah , Houston Peter , Greenblatt Adam , Lekoubou Alain , Lindhorst Scott , Cachia David , Olar Adriana , Kutluay Ekrem
Published: December 2019

Introduction:

Metastases to the brain (MB) occur in up to 30% of adults with cancer; of these, 15% to 35% may have seizures. We investigated clinical and pathologic associations with seizure and EEG findings in patients with MB, given the sparse literature in this area.

Methods:

We performed a retrospective chart review of adults with pathologically confirmed MB treated at a large tertiary care center between April 8, 2006, and December 14, 2018. Primary outcomes were odds of “chart-documented seizure” (CDS) in the full sample and EEG-captured seizure or any epileptiform discharges among those monitored on EEG.

Results:

We studied 187 patients with MB, of whom 55 (28.3%) were monitored on EEG. We found an overall CDS prevalence of 29.4% and an EEG-captured seizure of 18.9% among patients monitored on EEG. Of those monitored on EEG, 47.2% had epileptiform discharges. Adenocarcinoma pathology was associated with lower odds of CDS (odds ratio [OR] 0.50, 95% CI 0.26–0.96) and EEG-captured seizure (OR 0.09, 95% CI 0.01–0.87) versus other pathologies. When modeled separately, melanoma pathology was associated with CDS (OR 4.45, 95% CI 1.58–12.57) versus other pathologies. Hemorrhagic MB were associated with any epileptiform discharges (OR 5.50, 95% CI 1.65–18.37), regardless of pathology modeled. Increasing size of the largest dimension of the largest MB was associated with lower odds of CDS (OR 0.68, 95% CI 0.52–0.89 when adenocarcinoma modeled, OR 0.69, 95% CI 0.53–0.91 when melanoma modeled).

Conclusions:

Seizures and epileptiform discharges are common in patients with MB. Tumor size and pathology were significantly associated with CDS. Larger studies are needed for further analysis.
Epidemiology and virulence-associated genes of Clostridioides difficile isolates and factors associated with toxin EIA results at a university hospital in Japan
Authors: Okada Yuta , Yagihara Yuka , Wakabayashi Yoshitaka , Igawa Gene , Saito Ryoichi , Higurashi Yoshimi , Ikeda Mahoko , Tatsuno Keita , Okugawa Shu , Moriya Kyoji
Published: December 2019

Introduction.

Clostridioides difficile

is one of the most important nosocomial pathogens; however, reports regarding its clinical and molecular characteristics from Japan are scarce.

Aims. We studied the multilocus sequence typing (MLST)-based epidemiology and virulence-associated genes of isolates and the clinical backgrounds of patients from whom the isolates had been recovered.

Methods. A total of 105 stool samples tested in a

C. difficile

toxin enzyme immune assay (EIA) were analysed at the University of Tokyo Hospital from March 2013 to July 2014. PCR for MLST and the virulence-associated genes tcdA, tcdB, cdtA, cdtB and tcdC was performed on

C. difficile

isolates meeting our inclusion criteria following retrospective review of medical records. EIA-positive and EIA-negative groups with toxigenic strains underwent clinical and molecular background comparison.

Results. The toxigenic strains ST17, ST81, ST2, ST54, ST8, ST3, ST37 and ST53 and the non-toxigenic strains ST109, ST15 and ST100 were frequently recovered. The prevalence rate of tcdA-negative ST81 and ST37, endemic in China and Korea, was higher (11.4%) than that reported in North America and Europe, and hypervirulent ST1(RT027) and ST11(RT078) strains that occur in North America and Europe were not recovered. The linkage between the EIA results and cdt A/B positivity, tcdC deletion, or tcdA variation was absent among toxigenic strains. Compared with the 38 EIA-negative cases, the 36 EIA-positive cases showed that the patients in EIA-positive cases were older and more frequently had chronic kidney disease, as well as a history of beta-lactam use and proton pump inhibitor therapy.

Conclusion. In Japan, the prevalence rates for tcdA-negative strains are high, whereas the cdtA/B-positive strains are rare. EIA positivity is linked to older age, chronic kidney disease and the use of beta-lactams and proton pump inhibitors.
A Systematic Review on Psychological and Biological Mediators Between Adversity and Psychosis: Potential Targets for Treatment
Authors: Alameda Luis , Rodriguez Victoria , Carr Ewan , Aas Monica , Trotta Giulia , Marino Paolo , Vorontsova Natasha , Herane-Vives Andrés , Spinazzola Edoardo , Di Forti Marta , Morgan Craig , Murray Robin M
Published: December 2019

Various psychological and biological pathways have been proposed as mediators between childhood adverse events (CA) and psychosis. A systematic review of the evidence in this domain is needed. The aim of this work is to systematically review the evidence on psychological and biological mediators between CA and psychosis across the psychosis spectrum. This systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (registration number: CRD42018100846). Articles published between 1979 and July 2019 were identified through a literature search in OVID (PsychINFO; Medline and Embase). The evidence by each analysis and each study results are presented by group of mediator categories found in the review. The percentage of total effect mediated was calculated. 47 studies were included, with a total of 79,668 from general population (GP) and 3,189 from clinical samples. The quality of studies was judged as “fair”. Our results showed (i) solid evidence of mediation between CA and psychosis by negative cognitive schemas about the self, the world, and others (NS); by dissociation and other PTSD symptoms; (ii) evidence of al mediation through an affective pathway (affective dysregulation, anxiety, and depression) in GP; (iii) lack of studies exploring biological mediators. To conclude, we found evidence suggesting that various overlapping and not competing pathways contribute partially to the link between adversity and psychosis. Experiences of adversity, along with relevant mediators such as PTSD and mood related symptoms and NS, should be routinely assessed in patients with psychosis. Targeting such mediators through cognitive behavioural aproaches using trauma-focused therapy and/or pharmacological means could be a useful addition to the traditional treatment of positive symptoms.
Machine learning applied to atopic dermatitis transcriptome reveals distinct therapy-dependent modification of the keratinocyte immunophenotype
Authors: Clayton K. , Vallejo A. , Sirvent S. , Davies J. , Porter G. , Lim F. , Ardern-Jones M.R. , Polak M.E.
Published: December 2019

Background

Atopic dermatitis (AD) arises from a complex interaction between an impaired epidermal barrier, environmental exposures, and the infiltration of Th1/Th2/Th17/Th22 T cells. Transcriptomic analysis has advanced understanding of gene expression in cells and tissues. However, molecular quantitation of cytokine transcripts does not predict the importance of a specific pathway in AD or cellular responses to different inflammatory stimuli.

Objective

To understand changes in keratinocyte transcriptomic programmes in human cutaneous disease during development of inflammation and in response to treatment.

Methods

We performed in silico deconvolution of the whole-skin transcriptome. Using co-expression clustering and machine learning tools, we resolved the gene expression of bulk skin (n=7 datasets, n=406 samples), firstly, into unsupervised keratinocyte immune response phenotypes and, secondly, into 19 cutaneous cell signatures of purified populations from publicly available datasets.

Results

We identify three unique transcriptomic programmes in keratinocytes, KC1, KC2, KC17, characteristic to immune signalling from disease-associated helper T cells. We cross-validate those signatures across different skin inflammatory conditions and disease stages and demonstrate that the keratinocyte response during treatment is therapy dependent. Broad spectrum treatment with ciclosporin ameliorated the KC17 response in AD lesions to a non-lesional immunophenotype, without altering KC2. Conversely, the specific anti-Th2 therapy, dupilumab, reversed the KC2 immunophenotype.

Conclusion

Our analysis of transcriptomic signatures in cutaneous disease biopsies reveals the complexity of keratinocyte programming in skin inflammation and suggests that the perturbation of a single axis of immune signal alone may be insufficient to resolve keratinocyte immunophenotype abnormalities.
Biopsy-free prediction of prostate cancer aggressiveness using deep learning and radiology imaging
Authors: Khosravi Pegah , Lysandrou Maria , Eljalby Mahmoud , Brendel Matthew , Li Qianzi , Kazemi Ehsan , Barnes Josue , Zisimopoulos Pantelis , Sigaras Alexandros , Ricketts Camir , Meleshko Dimitri , Yat Andy , McClure Timothy D. , Robinson Brian D. , Sboner Andrea , Elemento Olivier , Chughtai Bilal , Hajirasouliha Iman
Published: December 2019

Magnetic Resonance Imaging (MRI) is routinely used to visualize the prostate gland and manage prostate cancer. The Prostate Imaging Reporting And Data System (PI-RADS) is used to evaluate the clinical risk associated with a potential tumor. However the PI-RADS score is subjective and its assessment varies between physicians. As a result, a definite diagnosis of prostate cancer requires a biopsy to obtain tissue for pathologic analysis. A prostate biopsy is an invasive procedure and is associated with complications, including hematospermia, hematuria, and rectal bleeding.

We hypothesized that an Artificial Intelligence (AI) can be trained on prostate cases where both imaging and biopsy are available to distinguish aggressive prostate cancer from non-aggressive lesions using MRI imaging only, that is, without the need for a biopsy.

Our computational method, named AI-biopsy, can distinguish aggressive prostate cancer from non-aggressive disease with an AUC of 0.855 and a 79.02% accuracy. We used Class Activation Maps (CAM) to highlight which regions of MRI images are being used by our algorithm for classification, and found that AI-biopsy generally focuses on the same regions that trained uro-radiolosts focus on, with a few exceptions. In conclusion, AI-biopsy provides a data-driven and reproducible way to assess cancer aggressiveness from MRI images and a personalized strategy to reduce the number of unnecessary biopsies.
Factors associated with access to Insecticide-Treated Nets and use of house modification in Bagamoyo and Ulanga districts, Tanzania
Authors: Odufuwa OG , Ross A , Mlacha YP , Juma O , Mmbaga S , Msellemu DF , Moore SJ
Published: December 2019

Background

Insecticide-treated Nets (ITNs) and house modifications are proven vector control tools, yet full coverage has frequently not been achieved. This study investigates factors associated with ITN access and use of house modification in Tanzania.

Methods

Baseline data from cross-sectional surveys was analysed from 7,240 households in Bagamoyo (60km north of Dar es Salaam) and 1,241 households in Ulanga (a remote rural area), from previous studies on spatial repellants and indoor residual spray evaluation. We estimated the associations between the outcomes: population access to ITNs, ITN per sleeping spaces, presence of window screens and closed eaves, and the covariates household size, age, gender, pregnancy, education, mosquito entry (doors and windows), house modification (window screens & closed eaves), mean distance to mosquito breeding sites and wealth using regression models.

Results

Population access to ITNs (households with one ITN per two potential people that stayed in the house the previous night of the survey) was 64% (56 - 71) and ITNs per sleeping spaces (households with enough ITNs to cover all sleeping spaces used the previous night of the survey) was 63% (54 - 72) in Bagamoyo, three years after the last Universal Coverage Campaigns (UCC). These findings are both lower than the 80% coverage target of the Tanzania National Malaria Strategic Plan (Tanzania NMSP). In Ulanga, population access to ITNs was 84% (78 - 91) and ITNs per sleeping spaces was 93% (89 - 97), one year after the last UCC. Household size was significantly associated with lower access to ITNs even shortly after UCC. House modification was common in both areas. In Bagamoyo, screened windows were more common than closed eaves (61% vs 14%) whereas in Ulanga more houses had closed eaves than window screens (55% vs 12%). Households in the poorest quintile were less likely to adopt window screening and closing eaves in Bagamoyo, this contrasts with Ulanga district where a greater proportion of poorer households blocked eaves with mud but were less likely to adopt screening.

Conclusion

Population access to ITN was substantially lower than the targets of the Tanzania NMSP after three years and lower among larger households after one year following ITN campaign. House modification was common in both areas, motivated by wealth. Improved access to ITNs and window screens through subsidy, especially among larger households, uptake of a combination of these two interventions may be maximized.
Gene expression data support the hypothesis that Isoetes rootlets are true roots and not modified leaves
Authors: Hetherington Alexander J. , Emms David M. , Kelly Steven , Dolan Liam
Published: December 2019

Rhizomorphic lycopsids are the land plant group that includes the first giant trees to grow on Earth and extant species in the genus Isoetes. Two mutually exclusive hypotheses account for the evolution of terminal rooting axes called rootlets among the rhizomorphic lycopsids. One hypothesis states that rootlets are true roots, like roots in other lycopsids. The other states that rootlets are modified leaves. Here we test predictions of each hypothesis by investigating gene expression in the leaves and rootlets of Isoetes echinospora. We assembled the de-novo transcriptome of axenically cultured I. echinospora. Gene expression signatures of I. echinospora rootlets and leaves were different. Furthermore, gene expression signatures of I. echinospora rootlets were similar to gene expression signatures of true roots of Selaginella moellendorffii and Arabidopsis thaliana. RSL genes which positively regulate cell differentiation in roots were either exclusively or preferentially expressed in the I. echinospora rootlets, S. moellendorffii roots and A. thaliana roots compared to the leaves of each respective species. Taken together, gene expression data from the de-novo transcriptome of I. echinospora are consistent with the hypothesis that Isoetes rootlets are true roots and not modified leaves.
Spinal Microglia Contribute to Sustained Inflammatory Pain via Amplifying Neuronal Activity
Authors: Gu Nan , Yi Min-Hee , Murugan Madhuvika , Xie Manling , Peng Jiyun , Eyo Ukpong B , Dong Hailong , Wu Long-Jun
Published: December 2019

Microglia are highly dynamic immune cells of the central nervous system (CNS). Microglial processes interact with neuronal elements constantly on the order of minutes. The functional significance of this acute microglia-neuron interaction and its potential role in the context of pain is still largely unknown. Here, we found that spinal microglia increased their process motility and electrophysiological reactivity within an hour after the insult in a mouse model of formalin-induced acute, sustained, inflammatory pain. Using an ablation strategy to specifically deplete resident microglia in the CNS, we demonstrate that microglia participate in formalin-induced acute sustained pain behaviors by amplifying neuronal activity in the spinal dorsal horn. Moreover, we identified that the P2Y12 receptor, which is specifically expressed in microglia in the CNS, was required for microglial function in formalin-induced pain. Taken together, our study provides a novel insight into the contribution of microglia and the P2Y12 receptor in acute, sustained, inflammatory pain that could be used for potential therapeutic strategies.
In vivo microstimulation with cathodic and anodic asymmetric waveforms modulates spatiotemporal calcium dynamics in cortical neuropil and pyramidal neurons of male mice
Authors: Stieger Kevin C. , Eles James R. , Ludwig Kip A. , Kozai Takashi D.Y.
Published: December 2019

Electrical stimulation has been critical in the development of an understanding of brain function and disease. Despite its widespread use and obvious clinical potential, the mechanisms governing stimulation in the cortex remain largely unexplored in the context of pulse parameters. Modeling studies have suggested that modulation of stimulation pulse waveform may be able to control the probability of neuronal activation to selectively stimulate either cell bodies or passing fibers depending on the leading polarity. Thus, asymmetric waveforms with equal charge per phase (i.e. increasing the leading phase duration and proportionately decreasing the amplitude) may be able to activate a more spatially localized or distributed population of neurons if the leading phase is cathodic or anodic, respectively. Here, we use two-photon and mesoscale calcium imaging of GCaMP6s expressed in excitatory pyramidal neurons of male mice to investigate the role of pulse polarity and waveform asymmetry on the spatiotemporal properties of direct neuronal activation with 10 Hz electrical stimulation. We demonstrate that increasing cathodic asymmetry effectively reduces neuronal activation and results in a more spatially localized subpopulation of activated neurons without sacrificing the density of activated neurons around the electrode. Conversely, increasing anodic asymmetry increases the spatial spread of activation and highly resembles spatiotemporal calcium activity induced by conventional symmetric cathodic stimulation. These results suggest that stimulation polarity and asymmetry can be used to modulate the spatiotemporal dynamics of neuronal activity thus increasing the effective parameter space of electrical stimulation to restore sensation and study circuit dynamics.

Significance Statement

Electrical stimulation has promise to restore sensation and motor function, as well as treat the symptoms of several neurological disorders. However, the mechanisms responsible for the beneficial effects of stimulation are not fully understood. This work supports modeling predictions by demonstrating that modulation of the stimulation waveform dramatically affects the spatial recruitment and activity level of neurons in vivo. These findings suggest that stimulation waveform symmetry represents a parameter that may be able to increase the dynamic range of stimulation applications. Further characterization of these parameters with frequency, and amplitude could provide further insight into the mechanisms of electrical stimulation.
Does metal pollution affect stoichiometry of soil-litter food webs?
Authors: Asselman Michel , Sobczyk Łukasz , Weiner January , Scheu Stefan , Rożen Anna
Published: December 2019

To date the field of ecological stoichiometry has focused mainly on aquatic systems concentrating on macro-elements. We investigated terrestrial systems and included microelements to study the elemental transfer in the detritivorous food web. We compared food webs of six sites differing in the type and degree of metal pollution along two forest transects contaminated with copper or zinc. We measured 11 elements in litter, herbivores, detritivores, predators and omnivores. Based on elemental concentrations of elements differences between trophic groups were visualized using PCA. At all sites litter C:N, C:P, C:K and C:Na ratios were higher than in animals. Invertebrate trophic groups were significantly different from each other in C:Cu, C:Zn and C:Ca ratios. The calculated resource:consumer N:P ratio suggests that invertebrates in studied forests are N limited and not P limited. Similar patterns at all sites suggests that metal pollution at the studied intensity slightly affects the transfer of elements in the terrestrial macro-invertebrate food web.
Combining multi-omics and drug perturbation profiles to identify novel treatments that improve disease phenotypes in spinal muscular atrophy
Authors: Meijboom Katharina E. , Volpato Viola , Monzón-Sandoval Jimena , Hoolachan Joseph M. , Hammond Suzan M. , Abendroth Frank , de Jong Olivier Gerrit , Hazell Gareth , Ahlskog Nina , Wood Matthew J.A. , Webber Caleb , Bowerman Melissa
Published: December 2019

Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by loss of survival motor neuron (SMN) protein. While SMN restoration therapies are beneficial, they are not a cure. We aimed to identify novel treatments to alleviate muscle pathology combining transcriptomics, proteomics and perturbational datasets. This revealed potential drug candidates for repurposing in SMA. One of the lead candidates, harmine, was further investigated in cell and animal models, improving multiple disease phenotypes, including SMN expression and lifespan. Our work highlights the potential of multiple, parallel data driven approaches for development of novel treatments for use in combination with SMN restoration therapies.
Limited phenological and pollinator-mediated isolation among selfing and outcrossingArabidopsis lyratapopulations
Authors: Gorman Courtney E. , Bond Lindsay , van Kleunen Mark , Dorken Marcel E. , Stift Marc
Published: December 2019

Transitions from outcrossing to selfing have been a frequent evolutionary shift in plants and clearly play a role in species divergence. However, many questions remain about the initial mechanistic basis of reproductive isolation during the evolution of selfing. For instance, how important are prezygotic pre-pollination mechanisms (e.g. changes in phenology and pollinator visitation) in maintaining reproductive isolation between newly arisen selfing populations and their outcrossing ancestors? To test whether changes in phenology and pollinator visitation isolate selfing populations ofArabidopsis lyratafrom outcrossing populations, we conducted a common garden experiment with plants from selfing and outcrossing populations as well as their F1 hybrids. Specifically, we asked whether there was isolation between outcrossing and selfing plants and their F1 hybrids through differences in 1) the timing or intensity of flowering; and/or 2) pollinator visitation. We found that phenology largely overlapped between plants from outcrossing and selfing populations. There were also no differences in pollinator preference related to mating system. Additionally, pollinators preferred to visit flowers on the same plant rather than exploring nearby plants, creating a large opportunity for self-fertilization. Overall, this suggests that prezygotic pre-pollination mechanisms do not strongly reproductively isolate plants from selfing and outcrossing populations ofArabidopsis lyrata.
OCTAVVS: A graphical toolbox for high-throughput preprocessing and analysis of vibrational spectroscopy imaging data
Authors: Troein Carl , Siregar Syahril , Op De Beeck Michiel , Peterson Carsten , Tunlid Anders , Persson Per
Published: December 2019

Modern vibrational spectroscopy techniques enable rapid collection of thousands of spectra in a single hyperspectral image, allowing researchers to resolve spatially heterogeneous samples down to a resolution of a fewμm. A number of algorithms have been developed to correct for effects such as atmospheric absorption, light scattering by cellular structures and varying baseline levels. Following such preprocessing, spectra are commonly decomposed and clustered to reveal informative patterns and subtle spectral changes. Several of these steps are slow, labor-intensive and require programming skills to make use of published algorithms and code. We here present a free and platform-independent graphical toolbox that allows rapid processing of large sets of spectroscopic images, including atmospheric correction and an algorithm for resonant Mie scattering with improved speed and stability. The software includes modules for decomposition into constituent spectra using the popular MCR-ALS algorithm, augmented by region-of-interest selection, as well as clustering and cluster annotation.
Trajectories of brain volume change over 13 years in chronic schizophrenia
Authors: Barth Claudia , Jørgensen Kjetil N. , Wortinger Laura A. , Nerland Stener , Jönsson Erik G. , Agartz Ingrid
Published: December 2019

Importance

Schizophrenia is a leading cause of disability worldwide, with an illness course that putatively deteriorates over time. Whether the notion of a progressive brain disease holds in its chronic stage is debated.

Objective

To investigate brain volume change and the impact of iatrogenic factors in chronic schizophrenia patients (duration of illness at baseline 16.17 ± 8.14 years) and controls over 13 years.

Design

Participants were recruited as part of the Human Brain Informatics study. Data acquisition took place between 1999 and 2018, including baseline, 5- and 13-years follow-up.

Setting

Naturalistic longitudinal case-control study.

Participants

The sample consisted of 143 participants, of whom 64 were patients with chronic schizophrenia (20% female, mean age at baseline 40.5 ± 7.7 years) and 79 healthy controls (37% female, mean age at baseline 42.8 ± 8.4 years). T1-weighted structural imaging and information about medication use were obtained at each time point.

Exposure

Antipsychotic medication and other prescribed drugs.

Main Outcome(s) and Measure(s)

Individual total and tissue-specific brain volumes, as well as two-time point percentage brain and ventricle volume change.

Results

Patients had lower total brain volume at baseline. Yet, trajectories in total brain volume and gray matter volume loss as well as ventricular enlargement did not differ relative to controls. White matter volume was similar between groups at baseline and 5-year but diverged between 5-year and 13-year follow-up, with accelerated loss in patients. While antipsychotic exposure did not show an association with brain volume loss over time, higher medication load was associated with lower brain volume across time points. Patients on second-generation antipsychotics alone showed lowest total brain volume, only after accounting for add-on drug use.

Conclusion and Relevance

We found limited evidence for progressive brain volume loss in chronic schizophrenia, beyond normal aging. Stable differences in patient brain volumes relative to controls may primarily occur during the first years of illness. All prescribed drugs need to be considered when examining the impact of antipsychotic medication on brain structure.

Key Points

Question

Is chronic schizophrenia associated with progressive brain volume loss beyond normal aging?

Findings

While brain volume was lower at baseline, patient trajectories of brain volume change over a 13-year follow-up period differed little from healthy individuals. Small effects indicated greater white matter volume loss in patients during the late phase of follow-up. Stable differences in patient brain volumes seem explicable by antipsychotic medication class and respective add-on drugs.

Meaning

We found limited evidence of progressive brain volume loss, beyond normal aging, in chronic schizophrenia over 13 years.
Phf15—a novel transcriptional repressor regulating inflammation in mouse microglia
Authors: Muroy Sandra E. , Timblin Greg A. , Preininger Marcela K. , Cedillo Paulina , Saijo Kaoru
Published: December 2019

Aim

Excessive microglial inflammation has emerged as a key player in mediating the effects of aging and neurodegeneration on brain dysfunction. Thus, there is great interest in discovering transcriptional repressors that can control this process. We aimed to examine whetherPhf15—one of the top differentially expressed genes in microglia during aging in humans—could regulate transcription of pro-inflammatory mediators in microglia.

Methods

RT-qPCR was used to assessPhf15mRNA expression in mouse brain during aging. Loss-of-function (shRNA-mediated knockdown (KD) and CRISPR/Cas9-mediated knockout (KO) ofPhf15)and gain-of-function (retroviral overexpression (OE) of murinePhf15cDNA) studies in a murine microglial cell line (SIM-A9) followed by immune activation with lipopolysaccharide (LPS) were used to determine the effect ofPhf15on pro-inflammatory factor (Tnfα, Il-1β, Nos2) mRNA expression. RNA-sequencing was used to determine global transcriptional changes afterPhf15knockout under basal conditions and after LPS stimulation.

Results

Phf15expression increases in mouse brain during aging, similar to humans. KD, KO and OE studies determined thatPhf15represses mRNA expression levels of pro-inflammatory mediators such asTnfα, Il-1βandNos2. Global transcriptional changes afterPhf15KO showed thatPhf15specifically represses genes related to the antiviral (type I interferon) response and cytokine production in microglia.

Conclusion

We provide the first evidence thatPhf15is an important transcriptional repressor of microglial inflammation, regulating the antiviral response and pro-inflammatory cytokine production. Importantly,Phf15regulates both basal and signal-dependent activation and controls the magnitude and duration of the microglial inflammatory response.
Exploring Food Contents in Scientific Literature with FoodMine
Authors: Hooton Forrest , Menichetti Giulia , Barabási Albert-László
Published: December 2019

Thanks to the many chemical and nutritional components it carries, diet critically affects human health. However, the currently available comprehensive databases on food composition cover only a tiny fraction of the total number of chemicals present in our food, focusing on the nutritional components essential for our health. Indeed, thousands of other molecules, many of which have well documented health implications, remain untracked. To explore the body of knowledge available on food composition, we built FoodMine, an algorithm that uses natural language processing to identify papers from PubMed that potentially report on the chemical composition of garlic and cocoa. After extracting from each paper information on the reported quantities of chemicals, we find that the scientific literature carries extensive information on the detailed chemical components of food that is currently not integrated in databases. Finally, we use unsupervised machine learning to create chemical embeddings, finding that the chemicals identified by FoodMine tend to have direct health relevance, reflecting the scientific community’s focus on health-related chemicals in our food.
Movement initiation and grasp representation in premotor and primary motor cortex mirror neurons
Authors: S.J. Jerjian , M. Sahani , A. Kraskov
Published: December 2019

Pyramidal tract neurons (PTNs) within macaque rostral ventral premotor cortex (F5) and primary motor cortex (M1) provide direct input to spinal circuitry and are critical for skilled movement control, but surprisingly, can also be active during passive action observation. We recorded from single neurons, including identified PTNs in the hand and arm area of primary motor cortex (M1) (n=189), and in premotor area F5 (n=115) of two adult male macaques, while they executed, observed, or simply withheld (NoGo) reach-to-grasp and hold actions. We found that F5 maintains a more sustained, similar representation of grasping actions during both execution and observation. In contrast, although some M1 neurons mirrored during the grasp and hold, M1 population activity during observation contained signatures of a withholding state. This suggests that M1 and its output may dissociates signals required for the initiation of movement from those associated with the representation of grasp in order to flexibly guide behaviour.

Significance Statement

Ventral premotor cortex (area F5) maintains a similar representation of grasping actions during both execution and observation. Primary motor cortex and its outputs dissociate between movement and non-movement states.
Design of DNA Origami Diamond Photonic Crystals
Authors: Park Sung Hun , Park Haedong , Hur Kahyun , Lee Seungwoo
Published: December 2019

Self-assembled photonic crystals have proven to be a fascinating class of photonic materials for non-absorbing structural colorizations over large areas and in diverse relevant applications, including tools for on-chip spectrometers and biosensors, platforms for reflective displays, and templates for energy devices. The most prevalent building blocks for the self-assembly of photonic crystals are spherical colloids and block copolymers (BCPs) due to the generic appeal of these materials, which can be crafted into large-area 3D lattices. However, due to the intrinsic limitations of these structures, these two building blocks are difficult to assemble into a direct rod-connected diamond lattice, which is considered to be a champion photonic crystal. Here, we present a DNA origami-route for a direct rod-connected diamond photonic crystal exhibiting a complete photonic bandgap (PBG) in the visible regime. Using a combination of electromagnetic, phononic, and mechanical numerical analyses, we identify (i) the structural constraints of the 50 megadalton-scale giant DNA origami building blocks that could self-assemble into a direct rod-connected diamond lattice with high accuracy, and (ii) the elastic moduli that are essentials for maintaining lattice integrity in a buffer solution. A solution molding process could enable the transformation of the as-assembled DNA origami lattice into a porous silicon- or germanium-coated composite crystal with enhanced refractive index contrast, in that a champion relative bandwidth for the photonic bandgap (i.e., 0.29) could become possible even for a relatively low volume fraction (i.e., 16 vol%).
Prenatal cannabis exposure and childhood outcomes: Results from the ABCD study
Authors: Paul Sarah E. , Hatoum Alexander , Fine Jeremy D. , Johnson Emma C. , Hansen Isabella , Karcher Nicole R. , Moreau Allison L. , Bondy Erin , Qu Yueyue , Carter Ebony B. , Rogers Cynthia E , Agrawal Arpana , Barch Deanna M. , Bogdan Ryan
Published: December 2019

Importance

In light of increasing cannabis use among pregnant women, the Surgeon General of the United States issued an advisory against the use of marijuana during pregnancy on August 29th, 2019.

Objective

To determine whether cannabis use during pregnancy is associated with adverse outcomes among offspring.

Design

Cross-sectional analysis of the baseline session of the ongoing longitudinal Adolescent Brain and Cognitive Development (ABCD) study.

Setting

Data were collected from 22 sites across the United States between 2016 and 2018.

Participants

Children ages 9-11 (n=11,489) and their parent or caregiver.

Exposure

Prenatal marijuana exposure prior to and following maternal knowledge of pregnancy.

Main Outcomes and Measures

Child psychopathology symptomatology (i.e., psychotic-like experiences and internalizing, externalizing, attention, thought, and social problems), cognition, sleep, birth weight, gestational age at birth, body mass index (BMI), and brain structure (i.e., total intracranial volume, white matter volume, gray matter volume). Covariates included familial (e.g., income, familial psychopathology), pregnancy (e.g., prenatal vitamin use, whether the pregnancy was planned), and child (e.g., birth weight, substance use) variables.

Results

Among 11,489 children (age 9.9±0.6 years; 47.78% female), 655 (5.70%) were prenatally exposed to cannabis in total. Marijuana use prior to (n=648; 5.64%) and following (n=242; 2.11%) maternal knowledge of pregnancy were associated with increased offspring psychopathology characteristics (i.e., psychotic-like experiences and internalizing, externalizing, attention, thought, social, and sleep problems) and BMI as well as reduced cognition, birth weight, and brain structure (i.e., total white and gray mater volumes; all psfdr<.007), but not gestational age at birth. Exposure following maternal knowledge of pregnancy remained significantly associated with psychopathology, cognition, and birth weight outcomes when including potentially confounding variables (all ps<0.046). All associations with exposure prior to maternal knowledge of pregnancy were nonsignificant when considering potentially confounding variables (all ps>0.06).

Conclusions and Relevance

Prenatal cannabis exposure, and its correlated factors, may increase risk for psychopathology and reduced cognition during middle childhood as well as reduced birthweight. Consistent with recent recommendations by the Surgeon General, marijuana use during pregnancy should be discouraged.
Impact of community treatment with ivermectin for the control of scabies on the prevalence of antibodies to Strongyloides stercoralis in children
Authors: Marks Michael , Gwyn Sarah , Toloka Hilary , Kositz Christian , Asugeni James , Asugeni Rowena , Diau Jason , Kaldor John M , Romani Lucia , Redman-MacLaren Michelle , MacLaren David , Solomon Anthony W , Mabey David CW , Steer Andrew C , Martin Diana
Published: December 2019

Prevalence of antibodies to Strongyloides stercoralis was measured in 0–12-year-olds using a bead-based immunoassay before and after ivermectin mass drug administration (MDA) for scabies in the Solomon Islands. Seroprevalence was 9.3% before and 5.1% after MDA (p = 0.019), demonstrating collateral benefits of scabies MDA in this setting.
A Genetically Encoded Trimethylsilyl 1D1H-NMR Probe for Conformation Change in Large Membrane Protein Complexes
Authors: Liu Qi , He Qing-tao , Lyu Xiao-xuan , Yang Fan , Zhu Zhong-liang , Xiao Peng , Yang Zhao , Zhang Feng , Yang Zhao-ya , Wang Xiao-yan , Sun Peng , Wang Qian-wen , Qu Chang-xiu , Gong Zheng , Lin Jing-Yu , Xu Zhen , Song Shao-le , Huang Shen-ming , Guo Sheng-chao , Han Ming-jie , Zhu Kong-kai , Chen Xin , Kahsai Alem W. , Xiao Kun-Hong , Kong Wei , Yu Xiao , Ruan Ke , Li Fa-hui , Niu Xiao-gang , Jin Chang-wen , Wang Jiangyun , Sun Jin-peng
Published: December 2019

While one dimensional1H nuclear magnetic resonance (1D1H-NMR) spectroscopy is one of the most important and convenient method for measuring conformation change in biomacromolecules, characterization of protein dynamics in large membrane protein complexes by 1D1H-NMR remains challenging, due to the difficulty of spectra assignment, low signal-to-noise ratio (S/N) and the need for large amount of protein. Here we report the site-specific incorporation of 4-trimethylsilyl phenylalanine (TMSiPhe) into proteins, through genetic code expansion inEscherichia colicells, and the measurement of multiple conformational states in membrane protein complex by 1D1H-NMR. The unique up-field1H-NMR chemical shift of TMSiPhe, highly efficient and specific incorporation of TMSiPhe enabled facile assignment of the TMSiPhe1H-NMR signal, and characterization of multiple conformational state in a 150 kilodalton (kD) membrane protein complex, using only 5 μM of protein and 20 min spectra accumulation time. This highly efficient and convenient methods should be broadly applicable for the investigation of dynamic conformation change of protein complexes.
Increased juvenile survival may not be universally linked to longevity: ecological, social and life-history drivers of age-specific mortality in birds
Authors: Mourocq Emeline , Drobniak Szymon M. , Griesser Michael
Published: December 2019

A classical prediction of the traditional evolutionary theories of ageing (tETA) is that longevity should be positively correlated with survival early on in life. However, large and unexplained variation exists in juvenile survival-longevity combinations. Here, we provide the first comparative study investigating the life-history, ecological and social correlates of juvenile survival, longevity and their combinations in 204 bird species. Overall, both measurements were positively correlated, but multiple survivals’ combinations evolved, some in accordance with tETA (“positive JS-L combinations”) while others contrasting it (“JS-L mismatches”). Positive JS-L combinations covaried with the pace of life proxies, whereas mismatching combinations covaried with the growing season length, where long growing seasons promoted juvenile survival, while short growing seasons promoted longevity. Interestingly, sociality explained only positive combinations, while life-history and ecological traits explained both positive and mismatching combinations. Overall, these findings challenge a main prediction of the tETA, and identify key evolutionary forces driving the coevolution between juvenile survival and longevity.
Efficient production of saffron crocins and picrocrocin inNicotiana benthamianausing a virus-driven system
Authors: Martí Maricarmen , Diretto Gianfranco , Aragonés Verónica , Frusciante Sarah , Ahrazem Oussama , Gómez-Gómez Lourdes , Daròs José-Antonio
Published: December 2019

Crocins and picrocrocin are glycosylated apocarotenoids responsible, respectively, for the color and the unique taste of the saffron spice, known as red gold due to its high price. Several studies have also shown the health-promoting properties of these compounds. However, their high costs hamper the wide use of these metabolites in the pharmaceutical sector. We have developed a virus-driven system to produce remarkable amounts of crocins and picrocrocin in adultNicotiana benthamianaplants in only two weeks. The system consists of viral clones derived from tobacco etch potyvirus that express specific carotenoid cleavage dioxygenase (CCD) enzymes fromCrocus sativusandBuddleja davidii. Metabolic analyses of infected tissues demonstrated that the sole virus-driven expression ofC. sativusCsCCD2L orB. davidiiBdCCD4.1 resulted in the production of crocins, picrocrocin and safranal. Using the recombinant virus that expressed CsCCD2L, accumulations of 0.2% of crocins and 0.8% of picrocrocin in leaf dry weight were reached in only two weeks. In an attempt to improve apocarotenoid content inN. benthamiana, co-expression of CsCCD2L with other carotenogenic enzymes, such asPantoea ananatisphytoene synthase (PaCrtB) and saffron β-carotene hydroxylase 2 (BCH2), was performed using the same viral system. This combinatorial approach led to an additional crocin increase up to 0.35% in leaves in which CsCCD2L and PaCrtB were co-expressed. Considering that saffron apocarotenoids are costly harvested from flower stigma once a year, and thatBuddlejaspp. flowers accumulate lower amounts, this system may be an attractive alternative for the sustainable production of these appreciated metabolites.
Two opposing hippocampus to prefrontal cortex pathways for the control of approach and avoidance behavior
Authors: Sánchez-Bellot Candela , MacAskill Andrew F.
Published: December 2019

The decision to either approach or avoid a potentially threatening environment is thought to rely upon complex connectivity between heterogenous neural populations in the ventral hippocampus and prefrontal cortex (PFC). However, how this circuitry can flexibly promote both approach or avoidance at different times has remained elusive. Here, we show that the projection to PFC is composed of two parallel circuits located in the superficial or deep hippocampal pyramidal layers. These circuits have unique upstream and downstream connectivity, and are differentially active during approach and avoidance behavior. The superficial population is preferentially connected to widespread PFC inhibitory interneurons, and its activation promotes exploration; while the deep circuit is connected to PFC pyramidal neurons and fast spiking interneurons, and its activation promotes avoidance. Together this provides a mechanism for regulation of behavior during approach avoidance conflict: through two specialized, parallel circuits that allow bidirectional hippocampal control of PFC.