bluuebunny/crossref_metadata_2025 huggingface dataset:
An Inexpensive Cardiovascular Flow Simulator for Cardiac Catheterization Procedure Using a Pulmonary Artery Catheter
Authors: Johnson Annika , Cupp Grace , Armour Nicholas , Warren Kyle , Stone Christopher , Lee Davin , Gilbert Nicholas , Hammond Chris , Moore John , Kang Youngbok (Abraham)
Published: October 2021

Cardiac catheterization associated with central vein cannulation can involve potential thrombotic and infectious complications due to multiple cannulation trials or improper placement. To minimize the risks, medical simulators are used for training. Simulators are also employed to test medical devices such as catheters before performing animal tests because they are more cost-effective and still reveal necessary improvements. However, commercial simulators are expensive, simplified for their purpose, and provide limited access sites. Inexpensive and anatomical cardiovascular simulators with central venous access for cannulation are sparse. Here, we developed an anatomically and physiologically accurate cardiovascular flow simulator to help train medical professionals and test medical devices. Our simulator includes an anatomical right atrium/ventricle, femoral and radial access sites, and considers the variability of arm position. It simulates physiological pulsatile blood flow with a setting for constant flow from 3 to 6 L/min and mimics physiological temperature (37°C). We demonstrated simulation by inserting a catheter into the system at radial/femoral access sites, passing it through the vasculature, and advancing it into the heart. We expect that our simulator can be used as an educational tool for cardiac catheterization as well as a testing tool that will allow for design iteration before moving to animal trials.
Bridging Microbial Functional Traits With Localized Process Rates at Soil Interfaces
Authors: Blagodatskaya Evgenia , Tarkka Mika , Knief Claudia , Koller Robert , Peth Stephan , Schmidt Volker , Spielvogel Sandra , Uteau Daniel , Weber Matthias , Razavi Bahar S.
Published: October 2021

In this review, we introduce microbially-mediated soil processes, players, their functional traits, and their links to processes at biogeochemical interfaces [e.g., rhizosphere, detritusphere, (bio)-pores, and aggregate surfaces]. A conceptual view emphasizes the central role of the rhizosphere in interactions with other biogeochemical interfaces, considering biotic and abiotic dynamic drivers. We discuss the applicability of three groups of traits based on microbial physiology, activity state, and genomic functional traits to reflect microbial growth in soil. The sensitivity and credibility of modern molecular approaches to estimate microbial-specific growth rates require further development. A link between functional traits determined by physiological (e.g., respiration, biomarkers) and genomic (e.g., genome size, number of ribosomal gene copies per genome, expression of catabolic versus biosynthetic genes) approaches is strongly affected by environmental conditions such as carbon, nutrient availability, and ecosystem type. Therefore, we address the role of soil physico-chemical conditions and trophic interactions as drivers of microbially-mediated soil processes at relevant scales for process localization. The strengths and weaknesses of current approaches (destructive, non-destructive, and predictive) for assessing process localization and the corresponding estimates of process rates are linked to the challenges for modeling microbially-mediated processes in heterogeneous soil microhabitats. Finally, we introduce a conceptual self-regulatory mechanism based on the flexible structure of active microbial communities. Microbial taxa best suited to each successional stage of substrate decomposition become dominant and alter the community structure. The rates of decomposition of organic compounds, therefore, are dependent on the functional traits of dominant taxa and microbial strategies, which are selected and driven by the local environment.
Culture-Independent Exploration of the Hypersaline Ecosystem Indicates the Environment-Specific Microbiome Evolution
Authors: Mehta Priyanka , Yadav Monika , Ahmed Vasim , Goyal Khushboo , Pandey Rajesh , Chauhan Nar Singh
Published: October 2021

Sambhar Salt Lake, situated in the state of Rajasthan, India is a unique temperate hypersaline ecosystem. Exploration of the salt lake microbiome will enable us to understand microbiome functioning in nutrient-deprived extreme conditions, as well as enrich our understanding of the environment-specific microbiome evolution. The current study has been designed to explore the Sambhar Salt Lake microbiome with a culture-independent multi-omics approach to define its metagenomic features and prevalent metabolic functionaries. The rRNA feature and protein feature-based phylogenetic reconstruction synchronously (R = 0.908) indicated the dominance of the archaea (Euryarchaeota) and bacteria (Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria). Metabolic reconstruction identified selective enrichment of the protein features associated with energy harvesting and stress tolerance (osmotic, oxidative, metal/metalloid, heat/cold, antibiotic, and desiccation). Metabolites identified with metabolome analysis confirmed physiological adaptation of the lake microbiome within a hypersaline and nutrient-deprived environment. Comparative metagenomics of the 212 metagenomes representing freshwater, alkaline, and saline ecosystem microbiome indicated the selective enrichment of the microbial groups and genetic features. The current study elucidates microbiome functioning within the nutrient-deprived harsh ecosystems. In summary, the current study harnessing the strength of multi-omics and comparative metagenomics indicates the environment-specific microbiome evolution.
Sea Ice Dynamics Drive Benthic Microbial Communities in McMurdo Sound, Antarctica
Authors: Currie Ashleigh A. , Marshall Alexis J. , Lohrer Andrew M. , Cummings Vonda J. , Seabrook Sarah , Cary S. Craig
Published: October 2021

Climate change is driving dramatic variability in sea ice dynamics, a key driver in polar marine ecosystems. Projected changes in Antarctica suggest that regional warming will force dramatic shifts in sea ice thickness and persistence, altering sea ice-associated primary production and deposition to the seafloor. To improve our understanding of the impacts of sea ice change on benthic ecosystems, we directly compared the benthic microbial communities underlying first-year sea ice (FYI) and multi-year sea ice (MYI). Using two tractable coastal habitats in McMurdo Sound, Antarctica, where FYI (Cape Evans) and MYI (New Harbour) prevail, we show that the structure and composition of the benthic microbial communities reflect the legacy of sea ice dynamics. At Cape Evans, an enrichment of known heterotrophic algal polysaccharide degrading taxa (e.g., Flavobacteriaceae, unclassified Gammaproteobacteria, and Rubritaleaceae) and sulfate-reducing bacteria (e.g., Desulfocapsaceae) correlated with comparatively higher chlorophyll a (14.2±0.8μgg−1) and total organic carbon content (0.33%±0.04), reflecting increased productivity and seafloor deposition beneath FYI. Conversely, at New Harbour, an enrichment of known archaeal (e.g., Nitrosopumilaceae) and bacterial (e.g., Woeseiaceae and Nitrospiraceae) chemoautotrophs was common in sediments with considerably lower chlorophyll a (1.0±0.24μgg−1) and total organic carbon content (0.17%±0.01), reflecting restricted productivity beneath MYI. We also report evidence of a submarine discharge of sub-permafrost brine from Taylor Valley into New Harbour. By comparing our two study sites, we show that under current climate-warming scenarios, changes to sea ice productivity and seafloor deposition are likely to initiate major shifts in benthic microbial communities, with heterotrophic organic matter degradation processes becoming increasingly important. This study provides the first assessment of how legacy sea ice conditions influence benthic microbial communities in Antarctica, contributing insight into sea ice–benthic coupling and ecosystem functioning in a polar environment.
The Effect of Allicin on the Proteome of SARS-CoV-2 Infected Calu-3 Cells
Authors: Mösbauer Kirstin , Fritsch Verena Nadin , Adrian Lorenz , Bernhardt Jörg , Gruhlke Martin Clemens Horst , Slusarenko Alan John , Niemeyer Daniela , Antelmann Haike
Published: October 2021

Allicin (diallyl thiosulfinate) is the major thiol-reactive organosulfur compound produced by garlic plants (Allium sativum) upon tissue damage. Allicin exerts its strong antimicrobial activity against bacteria and fungi via S-thioallylation of protein thiols and low molecular weight thiols. Here, we investigated the effect of allicin on SARS-CoV-2 infected Vero E6 and Calu-3 cells. Toxicity tests revealed that Calu-3 cells showed greater allicin tolerance, probably due to >4-fold higher GSH levels compared to the very sensitive Vero E6 cells. Exposure of infected Vero E6 and Calu-3 cells to biocompatible allicin doses led to a ∼60–70% decrease of viral RNA and infectious viral particles. Label-free quantitative proteomics was used to investigate the changes in the Calu-3 proteome after SARS-CoV-2 infection and the effect of allicin on the host-virus proteome. SARS-CoV-2 infection of Calu-3 cells caused a strong induction of the antiviral interferon-stimulated gene (ISG) signature, including several antiviral effectors, such as cGAS, Mx1, IFIT, IFIH, IFI16, IFI44, OAS, and ISG15, pathways of vesicular transport, tight junctions (KIF5A/B/C, OSBPL2, CLTCL1, and ARHGAP17) and ubiquitin modification (UBE2L3/5), as well as reprogramming of host metabolism, transcription and translation. Allicin treatment of infected Calu-3 cells reduced the expression of IFN signaling pathways and ISG effectors and reverted several host pathways to levels of uninfected cells. Allicin further reduced the abundance of the structural viral proteins N, M, S and ORF3 in the host-virus proteome. In conclusion, our data demonstrate the antiviral and immunomodulatory activity of biocompatible doses of allicin in SARS-CoV-2-infected cell cultures. Future drug research should be directed to exploit the thiol-reactivity of allicin derivatives with increased stability and lower human cell toxicity as antiviral lead compounds.
Genomic Epidemiology Reveals Multiple Introductions of Severe Acute Respiratory Syndrome Coronavirus 2 in Niigata City, Japan, Between February and May 2020
Authors: Wagatsuma Keita , Sato Ryosuke , Yamazaki Satoru , Iwaya Masako , Takahashi Yoshiki , Nojima Akiko , Oseki Mitsuru , Abe Takashi , Phyu Wint Wint , Tamura Tsutomu , Sekizuka Tsuyoshi , Kuroda Makoto , Matsumoto Haruki H. , Saito Reiko
Published: October 2021

The coronavirus disease 2019 (COVID-19) has caused a serious disease burden and poses a tremendous public health challenge worldwide. Here, we report a comprehensive epidemiological and genomic analysis of SARS-CoV-2 from 63 patients in Niigata City, a medium-sized Japanese city, during the early phase of the pandemic, between February and May 2020. Among the 63 patients, 32 (51%) were female, with a mean (±standard deviation) age of 47.9 ± 22.3 years. Fever (65%, 41/63), malaise (51%, 32/63), and cough (35%, 22/63) were the most common clinical symptoms. The median Ct value after the onset of symptoms lowered within 9 days at 20.9 cycles (interquartile range, 17–26 cycles), but after 10 days, the median Ct value exceeded 30 cycles (p < 0.001). Of the 63 cases, 27 were distributed in the first epidemic wave and 33 in the second, and between the two waves, three cases from abroad were identified. The first wave was epidemiologically characterized by a single cluster related to indoor sports activity spread in closed settings, which included mixing indoors with families, relatives, and colleagues. The second wave showed more epidemiologically diversified events, with most index cases not related to each other. Almost all secondary cases were infected by droplets or aerosols from closed indoor settings, but at least two cases in the first wave were suspected to be contact infections. Results of the genomic analysis identified two possible clusters in Niigata City, the first of which was attributed to clade S (19B by Nexstrain clade) with a monophyletic group derived from the Wuhan prototype strain but that of the second wave was polyphyletic suggesting multiple introductions, and the clade was changed to GR (20B), which mainly spread in Europe in early 2020. These findings depict characteristics of SARS-CoV-2 transmission in the early stages in local community settings during February to May 2020 in Japan, and this integrated approach of epidemiological and genomic analysis may provide valuable information for public health policy decision-making for successful containment of chains of infection.
Biosensor-Based Optimization of Cutinase Secretion by Corynebacterium glutamicum
Authors: Bakkes Patrick J. , Lenz Patrick , Müller Carolin , Bida Astrid , Dohmen-Olma Doris , Knapp Andreas , Oldiges Marco , Jaeger Karl-Erich , Freudl Roland
Published: October 2021

The industrial microbe Corynebacterium glutamicum is gaining substantial importance as a platform host for recombinant protein secretion. We recently developed a fluorescence-based (eYFP) C. glutamicum reporter strain for the quantification of Sec-dependent protein secretion by monitoring the secretion-related stress response and now demonstrate its applicability in optimizing the secretion of the heterologous enzyme cutinase from Fusarium solani pisi. To drive secretion, either the poor-performing PelSP or the potent NprESP Sec signal peptide from Bacillus subtilis was used. To enable easy detection and quantification of the secreted cutinase we implemented the split green fluorescent protein (GFP) assay, which relies on the GFP11-tag fused to the C-terminus of the cutinase, which can complement a truncated GFP thereby reconstituting its fluorescence. The reporter strain was transformed with different mutant libraries created by error-prone PCR, which covered the region of the signal peptide and the N-terminus of the cutinase. Fluorescence-activated cell sorting (FACS) was performed to isolate cells that show increased fluorescence in response to increased protein secretion stress. Five PelSP variants were identified that showed a 4- to 6-fold increase in the amount and activity of the secreted cutinase (up to 4,100 U/L), whereas two improved NprESP variants were identified that showed a ∼35% increase in secretion, achieving ∼5,500 U/L. Most of the isolated variants carried mutations in the h-region of the signal peptide that increased its overall hydrophobicity. Using site-directed mutagenesis it was shown that the combined mutations F11I and P16S within the hydrophobic core of the PelSP are sufficient to boost cutinase secretion in batch cultivations to the same level as achieved by the NprESP. Screening of a PelSP mutant library in addition resulted in the identification of a cutinase variant with an increased specific activity, which was attributed to the mutation A85V located within the substrate-binding region. Taken together the biosensor-based optimization approach resulted in a substantial improvement of cutinase secretion by C. glutamicum, and therefore represents a valuable tool that can be applied to any secretory protein of interest.
Detection and Monitoring of Mycobacterium leprae Infection in Nine Banded Armadillos (Dasypus novemcinctus) Using a Quantitative Rapid Test
Authors: Zhou Zijie , Pena Maria , van Hooij Anouk , Pierneef Louise , de Jong Danielle , Stevenson Roena , Walley Rachel , Corstjens Paul L. A. M. , Truman Richard , Adams Linda , Geluk Annemieke
Published: October 2021

Leprosy is an infectious disease caused by Mycobacterium leprae with tropism for skin and peripheral nerves. Incessant transmission in endemic areas is still impeding elimination of leprosy. Although detection of M. leprae infection remains a challenge in asymptomatic individuals, the presence of antibodies specific for phenolglycolipid-I (PGL-I) correlate with bacterial load. Therefore, serosurveillance utilizing field-friendly tests detecting anti-PGL-I antibodies, can be applied to identify those who may transmit bacteria and to study (reduction of) M. leprae transmission. However, serology based on antibody detection cannot discriminate between past and present M. leprae infection in humans, nor can it detect individuals carrying low bacillary loads. In humans, anti-PGL-I IgM levels are long-lasting and usually detected in more individuals than anti-PGL-I IgG levels. Inherent to the characteristically long incubation time of leprosy, IgM/IgG relations (antibody kinetics) in leprosy patients and infected individuals are not completely clear. To investigate the antibody response directly after infection, we have measured antibody levels by ELISA, in longitudinal samples of experimentally M. leprae infected, susceptible nine-banded armadillos (Dasypus novemcinctus). In addition, we assessed the user- and field-friendly, low-cost lateral flow assay (LFA) utilizing upconverting reporter particles (UCP), developed for quantitative detection of human anti-PGL-I IgM (UCP-LFA), to detect treatment- or vaccination-induced changes in viable bacterial load. Our results show that serum levels of anti-PGL-I IgM, and to a lesser extent IgG, significantly increase soon after experimental M. leprae infection in armadillos. In view of leprosy phenotypes in armadillos, this animal model can provide useful insight into antibody kinetics in early infection in the various spectral forms of human leprosy. The UCP-LFA for quantitative detection of anti-PGL-I IgM allows monitoring the efficacy of vaccination and rifampin-treatment in the armadillo leprosy model, thereby providing a convenient tool to evaluate the effects of drugs and vaccines and new diagnostics.
Exploring Refinement Strategies for Single Housing of Male C57BL/6JRj Mice: Effect of Cage Divider on Stress-Related Behavior and Hypothalamic-Pituitary-Adrenal-Axis Activity
Authors: Buckinx An , Van Schuerbeek Andries , Bossuyt Jo , Allaoui Wissal , Van Den Herrewegen Yana , Smolders Ilse , De Bundel Dimitri
Published: October 2021

Introduction: Single housing of laboratory mice is a common practice to meet experimental needs, or to avoid intermale aggression. However, single housing is considered to negatively affect animal welfare and may compromise the scientific validity of experiments. The aim of this study was to investigate whether the use of a cage with a cage divider, which avoids physical contact between mice while maintaining sensory contact, may be a potential refinement strategy for experiments in which group housing of mice is not possible.

Methods: Eight-week-old male C57BL/6JRj mice were single housed, pair housed or pair housed with a cage divider for four (experiment 1) or ten (experiment 2) weeks, after which we performed an open field test, Y-maze spontaneous alternation test, elevated plus maze test, an auditory fear conditioning task, and assessed responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis.

Results: Housing conditions did not affect body weight, exploratory activity, anxiety, working memory, fear memory processing or markers for HPA-axis functioning in either experiment 1 or experiment 2. There was an increased distance traveled in mice housed with a cage divider compared to pair housed mice after 4 weeks, and after 10 weeks mice housed with a cage divider made significantly more arm entries in the Y-maze spontaneous alternation test.

Conclusion: Taken together, our study did not provide evidence for robust differences in exploratory activity, anxiety, working memory and fear memory processing in male C57BL/6JRj mice that were single housed, pair housed or pair housed with a cage divider.
Quantifying the Landscape of Decision Making From Spiking Neural Networks
Authors: Ye Leijun , Li Chunhe
Published: October 2021

The decision making function is governed by the complex coupled neural circuit in the brain. The underlying energy landscape provides a global picture for the dynamics of the neural decision making system and has been described extensively in the literature, but often as illustrations. In this work, we explicitly quantified the landscape for perceptual decision making based on biophysically-realistic cortical network with spiking neurons to mimic a two-alternative visual motion discrimination task. Under certain parameter regions, the underlying landscape displays bistable or tristable attractor states, which quantify the transition dynamics between different decision states. We identified two intermediate states: the spontaneous state which increases the plasticity and robustness of changes of minds and the “double-up” state which facilitates the state transitions. The irreversibility of the bistable and tristable switches due to the probabilistic curl flux demonstrates the inherent non-equilibrium characteristics of the neural decision system. The results of global stability of decision-making quantified by barrier height inferred from landscape topography and mean first passage time are in line with experimental observations. These results advance our understanding of the stochastic and dynamical transition mechanism of decision-making function, and the landscape and kinetic path approach can be applied to other cognitive function related problems (such as working memory) in brain networks.
Health Conditions in Adults With Cerebral Palsy: The Association With CP Subtype and Severity of Impairments
Authors: Jonsson Ulrica , Eek Meta N. , Sunnerhagen Katharina Stibrant , Himmelmann Kate
Published: October 2021

Aim: To determine the prevalence of common health conditions in adults with cerebral palsy (CP) and to identify associations with the CP subtype or the severity of impairments.

Methods: A population-based, cross-sectional study of 153 adults with CP born from 1959 to 1978 (87 males, 66 females; median age 48 years 3 months, range 37–58 years; 41% with unilateral spastic, 36% bilateral spastic, 19% dyskinetic, and 4% with ataxic CP). Data was gathered through interviews, physical assessments, and medical record reviews.

Results: The most common health conditions in adults with CP were pain 65%, upper gastrointestinal disorders 33%, dysphagia 29%, epilepsy 29%, and depression 27%. Cerebral palsy subtype was significantly associated with the presence of pain (p = 0.029), gastrointestinal (p < 0.001), and respiratory disorders (p = 0.006). A more severe physical impairment was associated with a higher prevalence of gastrointestinal disorders (p < 0.001), respiratory disorders (p < 0.001), and pressure ulcers (p < 0.001). Intellectual disability was associated with a higher prevalence of gastrointestinal disorders (p < 0.001), pneumonia (p = 0.001) epilepsy (p = 0.001), and pressure ulcers (p < 0.001), but with a lower prevalence of pain (p < 0.004) and hypertension (p = 0.043).

Conclusion: The prevalence of several common health conditions is related to the CP subtype and severity of impairments, indicating that CP plays a role in the development of these health conditions. Follow-up of adults with CP needs to include not only impairments, but general health as well. Increased attention directed toward signs of gastrointestinal and respiratory disorders in individuals with either dyskinetic CP, gross motor function classification system (GMFCS) levels IV–V, or intellectual disability, is recommended.
Thyroid-Related Hormone Levels in Clinical Patients With Moderately Severe-to-Profound Sudden Sensorineural Hearing Loss: A Prospective Study
Authors: Zheng Zhong , Shen Ying , Xia Liang , Xiao Lili , Sun Yuanyuan , Wang Hui , Chen Zhengnong , Wu Yaqin , Shi Haibo , He Jingchun , Feng Yanmei , Yin Shankai
Published: October 2021

Objectives: Sudden sensorineural hearing loss (SSNHL) is a common otological emergency, causing a measure of hearing loss and affecting the quality of life. This study aims to investigate the association of thyroid-related hormone levels with moderately severe-to-profound SSNHL.

Methods: The study included 70 patients with moderately severe-to-profound SSNHL and 100 age- and sex-matched healthy controls. Peripheral venous blood samples were taken from the participants, and their thyroid-related hormone levels were measured at admission and 1 week after treatment.

Results: In moderately severe-to-profound SSNaHL patients, the concentrations of total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3), and thyroid-stimulating hormone (TSH) (all P < 0.05) were significantly lower than in the control group. The TT3, TT4, FT3, and TSH levels were significantly higher in the effective group than in the ineffective group (all P < 0.05). Linear correlation analysis revealed that TSH level (R = 0.707, P < 0.05) elevation after treatment successfully predicted a favorable outcome of hearing recovery. Logistic regression analyses suggested low FT3 and TSH levels to be independent occurrence predictors, while the increase of TSH level may be an independent favorable outcome predictor.

Conclusions: The results suggest that low FT3 and TSH levels are risk factors for moderately severe-to-profound SSNHL. By discovering the positive association between TSH elevation and hearing recovery, along with the potential novel predictors of FT3 and TSH, our study may contribute valuable insights to the research and treatment of moderately severe-to-profound SSNHL.
Repetitive T1 Imaging Influences Gray Matter Volume Estimations in Structural Brain Imaging
Authors: Broessner Gregor , Ellerbrock Isabel , Menz Mareike M. , Frank Florian , Verius Michael , Gaser Christian , May Arne
Published: October 2021

Voxel-based morphometry (VBM) is a widely used tool for studying structural patterns of brain plasticity, brain development and disease. The source of the T1-signal changes is not understood. Most of these changes are discussed to represent loss or possibly gain of brain gray matter and recent publications speculate also about non-structural changes affecting T1-signal. We investigated the potential of pain stimulation to ultra-short-term alter gray matter signal changes in pain relevant brain regions in healthy volunteers using a longitudinal design. Immediately following regional nociceptive input, we detected significant gray matter volume (GMV) changes in central pain processing areas, i.e. anterior cingulate and insula cortex. However, similar results were observed in a control group using the identical time intervals but without nociceptive painful input. These GMV changes could be reproduced in almost 100 scanning sessions enrolling 72 healthy individuals comprising repetitive magnetization-prepared rapid gradient-echo (MPRAGE) sequences. These data suggest that short-term longitudinal repetitive MPRAGE may produce significant GMV changes without any intervention. Future studies investigating brain plasticity should focus and specifically report a consistent timing at which time-point during the experiment the T1-weighted scan is conducted. There is a necessity of a control group for longitudinal imaging studies.
Serotonergic Antidepressants and Risk for Traumatic Intracranial Bleeding
Authors: Isokuortti Harri , Iverson Grant L. , Posti Jussi P. , Ruuskanen Jori O. , Brander Antti , Kataja Anneli , Nikula Milaja , Öhman Juha , Luoto Teemu M.
Published: October 2021

Background: Serotonergic antidepressants may predispose to bleeding but the effect on traumatic intracranial bleeding is unknown.

Methods: The rate of intracranial bleeding in patients with antidepressant medication was compared to patients not antidepressants in a cohort of patients with acute head injury. This association was examined by using a consecutive cohort of head trauma patients from a Finnish tertiary center emergency department (Tampere University Hospital, Tampere, Finland). All consecutive (2010–2012) adult patients (n = 2,890; median age = 58; male = 56%, CT-positive = 22%, antithrombotic medication users = 25%, antidepressant users = 10%) who underwent head CT due to head trauma in the emergency department were included.

Results: Male gender, GCS <15, older age, and anticoagulation were associated with an increased risk for traumatic intracranial bleeding. There were 17.8% of patients not taking antidepressants and 18.3% of patients on an antidepressant who had traumatic intracranial bleeding (p = 0.830). Among patients who were taking antithrombotic medication, 16.6% of the patients not taking antidepressant medication, and 22.5% of the patients taking antidepressant medication, had bleeding (p = 0.239). In a regression analysis, traumatic intracranial hemorrhage was not associated with antidepressant use.

Conclusions: Serotonergic antidepressant use was not associated with an increased risk of traumatic intracranial hemorrhage.
Brain Structural Alterations, Diabetes Biomarkers, and Cognitive Performance in Older Adults With Dysglycemia
Authors: Oh Dae Jong , Jung Ji-Jung , Shin Seong A. , Kim Hairin , Park Soowon , Sohn Bo Kyung , Koo Bo Kyung , Moon Min Kyong , Kim Yu Kyeong , Lee Jun-Young
Published: October 2021

Despite the high risk of dementia in older adults with type 2 diabetes, the neuroanatomical correlates of cognitive dysfunction that are particularly affected by diabetes are not well characterized. This study is aimed to examine the structural brain alterations in dysglycemic older adults. Using voxel-based morphometric and tract-based spatial statistics, we examined changes in gray matter volume, white matter volume, and microstructural integrity in older adults with prediabetes and diabetes. We also assessed the correlation of these structural changes with diabetes biomarkers and cognitive performance. A total of 74 non-demented older adults (normal, n = 14; prediabetes, n = 37; and diabetes, n = 23) participated in this study and underwent structural and diffusion magnetic resonance imaging (MRI) scans and neuropsychological tests. Subjects with diabetes showed reduced volume of cerebellar gray matter and frontal white matter and diffuse white matter dysintegrity, while those with prediabetes only showed reduced volume of insular gray matter. Atrophic changes in the cerebellum and frontal lobe and frontal white matter dysintegrity were correlated with chronic hyperglycemia and insulin resistance and worse performance in verbal memory recognition and executive function tests. Our findings suggest that chronic hyperglycemia and insulin resistance may alter brain structures forming the fronto-cerebellar network, which may cause cognitive dysfunction in older adults.
Development of the Relationships Among Dynamic Balance Control, Inter-limb Coordination, and Torso Coordination During Gait in Children Aged 3–10 Years
Authors: Mani Hiroki , Miyagishima Saori , Kozuka Naoki , Inoue Takahiro , Hasegawa Naoya , Asaka Tadayoshi
Published: October 2021

Knowledge about the developmental process of dynamic balance control comprised of upper arms and upper legs coordination and trunk and pelvis twist coordination is important to advance effective balance assessment for abnormal development. However, the mechanisms of these coordination and stability control during gait in childhood are unknown.This study examined the development of dynamic postural stability, upper arm and upper leg coordination, and trunk and pelvic twist coordination during gait, and investigated the potential mechanisms integrating the central nervous system with inter-limb coordination and trunk and pelvic twist coordination to control extrapolated center of the body mass (XCOM). This study included 77 healthy children aged 3–10 years and 15 young adults. The child cohort was divided into four groups by age: 3–4, 5–6, 7–8, and 9–10 years. Participants walked barefoot at a self-selected walking speed along an 8 m walkway. A three-dimensional motion capture system was used for calculating the XCOM, the spatial margin of stability (MoS), and phase coupling movements of the upper arms, upper legs, trunk, and pelvic segments. MoS in the mediolateral axis was significantly higher in the young adults than in all children groups. Contralateral coordination (ipsilateral upper arm and contralateral upper leg combination) gradually changed to an in-phase pattern with increasing age until age 9 years. Significant correlations of XCOMML with contralateral coordination and with trunk and pelvic twist coordination (trunk/pelvis coordination) were found. Significant correlations between contralateral coordination and trunk/pelvis coordination were observed only in the 5–6 years and at 7–8 years groups.Dynamic postural stability during gait was not fully mature at age 10. XCOM control is associated with the development of contralateral coordination and trunk and pelvic twist coordination. The closer to in-phase pattern of contralateral upper limb coordination improved the XCOM fluctuations. Conversely, the out-of-phase pattern (about 90 degrees) of the trunk/pelvis coordination increased theXCOM fluctuation. Additionally, a different control strategy was used among children 3–8 years of age and individuals over 9 years of age, which suggests that 3–4-year-old children showed a disorderly coordination strategy between limb swing and torso movement, and in children 5–8 years of age, limb swing depended on trunk/pelvis coordination.
Tinnitus Is Associated With Improved Cognitive Performance in Non-hispanic Elderly With Hearing Loss
Authors: Hamza Yasmeen , Zeng Fan-Gang
Published: October 2021

Because hearing loss is a high-risk factor for cognitive decline, tinnitus, a comorbid condition of hearing loss, is often presumed to impair cognition. The present cross-sectional study aimed to delineate the interaction of tinnitus and cognition in the elderly with and without hearing loss after adjusting for covariates in race, age, sex, education, pure tone average, hearing aids, and physical well-being. Participants included 643 adults (60–69 years old; 51.3% females) from the National Health and Nutrition Examination Survey (NHANES, 2011–2012), and 1,716 (60–69 years old; 60.4% females) from the Hispanic Community Health Study (HCHS, 2008–2011). Multivariable linear and binary logistic regression was used to assess the association between tinnitus and cognition in the two sub-cohorts of normal hearing (NHANES, n = 508; HCHS, n = 1264) and hearing loss (NHANES, n = 135; HCHS, n = 453). Cognitive performance was measured as a composite z-score from four cognitive tests: The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD)-word learning, CERAD-animal fluency, CERAD-word list recall, and the digit symbol substitution test (DSST) in NHANES, and a comparable Hispanic version of these four tests in HCHS. Multivariable linear regression revealed no association between tinnitus and cognition, except for the NHANES (non-Hispanic) participants with hearing loss, where the presence of tinnitus was associated with improved cognitive performance (Mean = 0.3; 95% CI, 0.1–0.5; p, 0.018). Using the 25th percentile score of the control (i.e., normal hearing and no tinnitus) as a threshold for poor cognitive performance, the absence of tinnitus increased the risk for poor cognitive performance (OR = 5.6, 95% CI, 1.9–17.2; p, 0.002). Sensitivity analysis found a positive correlation between tinnitus duration and cognitive performance in the NHANES cohort [F(4,140), 2.6; p, 0.037]. The present study finds no evidence for the assumption that tinnitus impairs cognitive performance in the elderly. On the contrary, tinnitus is associated with improved cognitive performance in the non-Hispanic elderly with hearing loss. The present result suggests that race be considered as an important and relevant factor in the experimental design of tinnitus research. Future longitudinal and imaging studies are needed to validate the present findings and understand their mechanisms.
Efficacy Evaluation of Neurofeedback-Based Anxiety Relief
Authors: Chen Chao , Xiao Xiaolin , Belkacem Abdelkader Nasreddine , Lu Lin , Wang Xin , Yi Weibo , Li Penghai , Wang Changming , Sha Sha , Zhao Xixi , Ming Dong
Published: October 2021

Anxiety disorder is a mental illness that involves extreme fear or worry, which can alter the balance of chemicals in the brain. This change and evaluation of anxiety state are accompanied by a comprehensive treatment procedure. It is well-known that the treatment of anxiety is chiefly based on psychotherapy and drug therapy, and there is no objective standard evaluation. In this paper, the proposed method focuses on examining neural changes to explore the effect of mindfulness regulation in accordance with neurofeedback in patients with anxiety. We designed a closed neurofeedback experiment that includes three stages to adjust the psychological state of the subjects. A total of 34 subjects, 17 with anxiety disorder and 17 healthy, participated in this experiment. Through the three stages of the experiment, electroencephalography (EEG) resting state signal and mindfulness-based EEG signal were recorded. Power spectral density was selected as the evaluation index through the regulation of neurofeedback mindfulness, and repeated analysis of variance (ANOVA) method was used for statistical analysis. The findings of this study reveal that the proposed method has a positive effect on both types of subjects. After mindfulness adjustment, the power map exhibited an upward trend. The increase in the average power of gamma wave indicates the relief of anxiety. The enhancement of the wave power represents an improvement in the subjects’ mindfulness ability. At the same time, the results of ANOVA showed thatP< 0.05, i.e., the difference was significant. From the aspect of neurophysiological signals, we objectively evaluated the ability of our experiment to relieve anxiety. The neurofeedback mindfulness regulation can effect on the brain activity pattern of anxiety disorder patients.
Development and Verification of Glutamatergic Synapse-Associated Prognosis Signature for Lower-Grade Gliomas
Authors: Ye Liguo , Xu Yang , Hu Ping , Wang Long , Yang Ji’an , Yuan Fan’en , Wang Yixuan , Zhang Chunyu , Tian Daofeng , Chen Qianxue
Published: October 2021

Background: Lower-grade glioma (LGG) is the most common histology identified in gliomas, a heterogeneous tumor that may develop into high-grade malignant glioma that seriously shortens patient survival time. Recent studies reported that glutamatergic synapses might play an essential role in the progress of gliomas. However, the role of glutamatergic synapse-related biomarkers in LGG has not been systemically researched yet.

Methods: The mRNA expression data of glioma and normal brain tissue were obtained from The Cancer Genome Atlas database and Genotype-Tissue Expression, respectively, and the Chinese Glioma Genome Atlas database was used as a validation set. Difference analysis was performed to evaluate the expression pattern of glutamatergic synapse-related genes (GSRGs) in LGG. The least absolute shrinkage and selection operator (LASSO) Cox regression was applied to construct the glutamatergic synapse-related risk signature (GSRS), and the risk score of each LGG sample was calculated based on the coefficients and expression value of selected GSRGs. Univariate and multivariate Cox regression analyses were used to investigate the prognostic value of risk score. Immunity profile and single-sample gene set enrichment analysis (ssGSEA) were performed to explore the association between risk score and the characters of tumor microenvironment in LGG. Gene set variation analysis (GSVA) was performed to investigate the potential pathways related to GSRS. The HPA database and real-time PCR were used to identify the expression of hub genes identified in GSRS.

Results: A total of 22 genes of 39 GSRGs were found differentially expressed among normal and LGG samples. Through the LASSO algorithm, 14-genes GSRS constructed were associated with the prognosis and clinicopathological features of patients with LGG. Furthermore, the risk score level was significantly positively correlated with the infiltrating level of immunosuppressive cells, including M2 macrophages and regulatory T cells. GSVA identified a series of cancer-related pathways related to GSRS, such as P13K-AKT and P53 pathways. Moreover, ATAD1, NLGN2, OXTR, and TNR, hub genes identified in GSRS, were considered as potential prognostic biomarkers in LGG.

Conclusion: A 14-genes GSRS was constructed and verified in this study. We provided a novel insight into the role of GSRS in LGG through a series of bioinformatics methods.
Association Between the Nutritional Risk and the Survival Rate in Newly Diagnosed GIST Patients
Authors: Ding Ping'an , Guo Honghai , Yang Peigang , Sun Chenyu , Tian Yuan , Liu Yang , Li Yong , Zhao Qun
Published: October 2021

Background: Currently, the incidence of gastrointestinal stromal tumors (GIST) is increasing rapidly worldwide. Malnutrition may increase the risk of perioperative complications and affect the prognosis of patients. However, previous studies on the nutritional status of GIST patients and its impact on prognosis are limited. Therefore, this study aims to explore the incidence of malnutrition in newly diagnosed GIST patients, the proportion of participants in need of nutritional intervention, and the relationship between nutritional status and overall survival (OS).

Methods: We retrospectively analyzed the clinical data of GIST patients treated in our hospital from January 2014 to January 2018. Nutritional Risk Screening 2002 (NRS2002) and Patient-Generated Subjective Global Assessment (PG-SGA) were used to assess the nutritional status of all patients. This study was to investigate the clinical significance of PG-SGA by analyzing the relationship between PG-SGA score and OS.

Results: A total of 1,268 newly diagnosed GIST patients were included in this study, of which 77.76% were at risk of malnutrition (NRS2002 score ≥ 3), and the incidence of malnutrition was 10.09% (PG-SGA score ≥ 4). Meanwhile, we found 2.29% of the patients required urgent nutritional support (PG-SGA score ≥ 9). Multivariate analysis showed that age (p = 0.013), BMI (p = 0.001), weight loss (p = 0.001), anemia (p = 0.005), pre-albumin (p = 0.010), albumin (p = 0.002), tumor location (p = 0.001), tumor size (p = 0.002), and NIH classification (p = 0.001) were risk factors for nutritional status. The prognosis was significantly in GIST patients with different PG-SGA score at admission (p < 0.05).

Conclusion: This study suggested that malnutrition is common in newly diagnosed GIST patients, and the higher the PG-SGA score, the worse the clinical outcome.
Diagnostic and Prognostic Significances of SOX9 in Thymic Epithelial Tumor
Authors: Yuan Xiaodong , Huang Lei , Luo Wenwu , Zhao Yufei , Nashan Björn , Yu Fazhi , Liu Yun
Published: October 2021

Background

Thymic epithelial tumors (TETs) are rare tumors originating from the thymic epithelial cells. SOX9, a member of the family of SOX (SRY-related high-mobility group box) genes, has been considered as an oncogene and therapeutic target in various cancers. However, its role in TETs remains uncertain.

Methods

Using the immunohistochemistry method, the expression of SOX9 was analyzed in TETs tissues, including 34 thymoma (8 cases with type A, 6 with type AB, 6 with type B1, 9 with type B2, and 5 with type B3 thymomas) and 20 thymic cancer tissues and the clinicopathologic and prognostic significances were evaluated. Further bioinformatics analysis of gene expression profiles of thymomas with high and low SOX9 expressions and the corresponding survival analyses were based on the thymoma cases identified in The Cancer Genome Atlas (TCGA) database, with the median expression level of SOX9 selected as cutoff.

Results

Immunohistochemistry staining showed that SOX9 was highly expressed in the nuclei of the epithelial cells of the Hassall’s corpuscles and of the TET tumor cells. SOX9 expression was significantly associated with histological type and high expression indicated unfavorable clinical outcomes of thymomas. Bioinformatics analysis revealed that genes positively associated with SOX9 expression were mapped in proteoglycans in cancer, cell adhesion molecules, and molecules involved in extracellular matrix-receptor interaction and the TGF-β signaling pathway, and that genes negatively associated with SOX9 expression were mapped in molecules involved in primary immunodeficiency, the T cell receptor signaling pathway, Th17 cell differentiation, PD-L1 expression, and the PD-1 checkpoint pathway in cancer. In addition, SOX9 expression was positively associated with POU2F3 and TRPM5 expressions, the master regulators of tuft cells, suggesting that high SOX9 expression might be associated with the tuft cell phenotype of thymomas. Moreover, high SOX9 expression was associated with immune dysregulation of thymoma, and M2 macrophage significantly dominated in the high SOX9 expression group.

Conclusion

SOX9 may serve as a diagnostic and prognostic marker for TETs. Notably, high SOX9 expression in TETs may indicate a tuft cell phenotype and an immune suppressive microenvironment of thymomas.
Recombinant Human Thrombopoietin Accelerates the Recovery of Platelet in Patients With Lower-Risk Myelodysplastic Syndrome: A Proof-of-Concept Study
Authors: Yang Yuan , Tang Zengwei , Ji Jiang , Yang Chen , Chen Miao , Han Bing
Published: October 2021

Aim

The effect of recombinant human thrombopoietin (rhTPO) is largely unknown in lower-risk myelodysplastic syndrome (LR-MDS). This study aimed at investigating the safety and efficacy of rhTPO in patients with LR-MDS.

Methods

LR-MDS patients receiving stanozolol (2 mg, t.i.d.) and supportive care alone (non-rhTPO) or additional rhTPO were enrolled in this study prospectively. rhTPO was given at 15,000 U (q.d.) for 7 days/month for at least 3 months. Patients stopped rhTPO if the platelet count was higher than 50 × 109/L or had no effects after 3 months of treatment. The overall response (OR), complete response (CR), platelet response, side effects, clone evolution, and clinical outcome were evaluated.

Result

Thirty-five patients were enrolled: 20 (57.1%) patients in the rhTPO group and 15 (42.9%) patients in the non-rhTPO group. The demographic and baseline characteristics were balanced between the two groups. Platelet response was higher at 1 and 2 months as compared with that in the non-rhTPO group (p = 0.006 and p = 0.001, respectively). Meanwhile, the rhTPO group had a shorter time to achieve a platelet transfusion-free state compared with the non-rhTPO group (p = 0.034). Hematologic response was higher at 1 and 2 months compared with that in the non-rhTPO group (p = 0.006 and p = 0.001, respectively). There was no significant difference in the overall response or complete response at 1, 2, 3, 6, and 12 months between the two groups. One patient in the rhTPO group evolved into higher-risk MDS at 9 months. No significant difference in disease progression, infection, gastrointestinal disorders, or drug-related liver/renal injuries was found between the two groups (p > 0.05).

Conclusion

Adding short-term rhTPO can accelerate the early platelet response and decrease platelet transfusion, with no obvious side effects.

Clinical Trial Registration

https://clinicaltrials.gov/ct2/show/NCT04324060?cond=NCT04324060&draw=2, identifier NCT04324060