bluuebunny/crossref_metadata_2025 huggingface dataset:
Indoleamine 2, 3 Dioxygenase 1 Impairs Chondrogenic Differentiation of Mesenchymal Stem Cells in the Joint of Osteoarthritis Mice Model
Authors: Alahdal Murad , Huang Rongxiang , Duan Li , Zhiqin Deng , Hongwei Ouyang , Li Wencui , Wang Daping
Published: December 2021

Osteoarthritis (OA) is a serious joint inflammation that leads to cartilage degeneration and joint dysfunction. Mesenchymal stem cells (MSCs) are used as a cell-based therapy that showed promising results in promoting cartilage repair. However, recent studies and clinical trials explored unsatisfied outcomes because of slow chondrogenic differentiation and increased calcification without clear reasons. Here, we report that the overexpression of indoleamine 2,3 dioxygenase 1 (IDO1) in the synovial fluid of OA patients impairs chondrogenic differentiation of MSCs in the joint of the OA mice model. The effect of MSCs mixed with IDO1 inhibitor on the cartilage regeneration was tested compared to MSCs mixed with IDO1 in the OA animal model. Further, the mechanism exploring the effect of IDO1 on chondrogenic differentiation was investigated. Subsequently, miRNA transcriptome sequencing was performed for MSCs cocultured with IDO1, and then TargetScan was used to verify the target of miR-122-5p in the SF-MSCs. Interestingly, we found that MSCs mixed with IDO1 inhibitor showed a significant performance to promote cartilage regeneration in the OA animal model, while MSCs mixed with IDO1 failed to stimulate cartilage regeneration. Importantly, the overexpression of IDO1 showed significant inhibition to Sox9 and Collagen type II (COL2A1) through activating the expression of β-catenin, since inhibiting of IDO1 significantly promoted chondrogenic signaling of MSCs (Sox9, COL2A1, Aggrecan). Further, miRNA transcriptome sequencing of SF-MSCs that treated with IDO1 showed significant downregulation of miR-122-5p which perfectly targets Wnt1. The expression of Wnt1 was noticed high when IDO1 was overexpressed. In summary, our results suggest that IDO1 overexpression in the synovial fluid of OA patients impairs chondrogenic differentiation of MSCs and cartilage regeneration through downregulation of miR-122-5p that activates the Wnt1/β-catenin pathway.
Gill Transcriptomic Responses to Toxin-producing Alga Prymnesium parvum in Rainbow Trout
Authors: Clinton Morag , Król Elżbieta , Sepúlveda Dagoberto , Andersen Nikolaj R. , Brierley Andrew S. , Ferrier David E. K. , Hansen Per Juel , Lorenzen Niels , Martin Samuel A. M.
Published: December 2021

The gill of teleost fish is a multifunctional organ involved in many physiological processes, including protection of the mucosal gill surface against pathogens and other environmental antigens by the gill-associated lymphoid tissue (GIALT). Climate change associated phenomena, such as increasing frequency and magnitude of harmful algal blooms (HABs) put extra strain on gill function, contributing to enhanced fish mortality and fish kills. However, the molecular basis of the HAB-induced gill injury remains largely unknown due to the lack of high-throughput transcriptomic studies performed on teleost fish in laboratory conditions. We used juvenile rainbow trout (Oncorhynchus mykiss) to investigate the transcriptomic responses of the gill tissue to two (high and low) sublethal densities of the toxin-producing alga Prymnesium parvum, in relation to non-exposed control fish. The exposure time to P. parvum (4–5 h) was sufficient to identify three different phenotypic responses among the exposed fish, enabling us to focus on the common gill transcriptomic responses to P. parvum that were independent of dose and phenotype. The inspection of common differentially expressed genes (DEGs), canonical pathways, upstream regulators and downstream effects pointed towards P. parvum-induced inflammatory response and gill inflammation driven by alterations of Acute Phase Response Signalling, IL-6 Signalling, IL-10 Signalling, Role of PKR in Interferon Induction and Antiviral Response, IL-8 Signalling and IL-17 Signalling pathways. While we could not determine if the inferred gill inflammation was progressing or resolving, our study clearly suggests that P. parvum blooms may contribute to the serious gill disorders in fish. By providing insights into the gill transcriptomic responses to toxin-producing P. parvum in teleost fish, our research opens new avenues for investigating how to monitor and mitigate toxicity of HABs before they become lethal.
Multi-Indicator Harvest Strategies for Data-Limited Fisheries: A Practitioner Guide to Learning and Design
Authors: Harford William J. , Amoroso Ricardo , Bell Richard J. , Caillaux Matias , Cope Jason Marc , Dougherty Dawn , Dowling Natalie Anne , Hurd Frank , Lomonico Serena , Nowlis Josh , Ovando Dan , Parma Ana M. , Prince Jeremy D. , Wilson Jono R.
Published: December 2021

As the world population grows, fisheries practitioners will be under increased pressure to address global challenges in data-limited fisheries management. With a focus on addressing localized and case-specific management needs, we provide a practical guide to the design and development of multi-indicator frameworks for fishery management. In a data-limited context, indicators are observations or estimates of the state of the fishery resource that are typically proxies for variables of interest, rather than quantities such as stock biomass estimated from data-rich stock assessments. Indicator frameworks structure the integration and interpretation of indicators to guide tactical fishery decision-making, often when the application of more formal analytical assessments is not feasible, yet where indicators in combination provide insight into stock status. With a focus on multi-indicator frameworks, we describe a pragmatic approach for their development via a set of organizational steps, considering a wide spectrum of types and severity of information limitations. We highlight where multi-indicator frameworks can be insightful and informative in relation to single indicator approaches but also point to potential pitfalls, with emphasis on critical evaluation and detection of performance flaws during the design phase using methods such as management strategy evaluation.
A Multi-Faceted Approach to Understand How Resource Diversity Can Mediate the Coexistence of Cryptic Marine Nematode Species
Authors: Guden Rodgee Mae , Derycke Sofie , Moens Tom
Published: December 2021

Based on the principle of competitive exclusion, species occupying the same ecological niche cannot stably coexist due to strong interspecific competition for resources. Niche diversification, for instance through resource partitioning, may alleviate competition. Here, we investigate the effects of resource diversity on foraging behavior, fitness and interspecific interactions of four cryptic bacterivorous nematode species (Pm I–IV) of the Litoditis marina species complex with sympatric field distributions. Three resource (bacteria) diversity levels (low, medium, high) were used as food treatments and compared to a treatment with only Escherichia coli as food. Differences in taxis to food existed between the cryptic species and between bacterial mixtures of different diversity: all the cryptic species except Pm I showed higher attraction toward medium-diversity food. Furthermore, the cryptic species of L. marina generally exhibited higher fitness on a more diverse food resource. Resource diversity also impacted the interspecific interactions between the cryptic species. Our results show that resource diversity can alter the interspecific interactions among the cryptic species of L. marina, indicating that competitive equilibria between species are very context-dependent. Although a considerable body of evidence supports the hypotheses (e.g., “variance-in-edibility” hypothesis and the “dilution hypothesis” or “resource concentration hypothesis”) which predict a negative impact on consumers when resource diversity is increased, the benefits of a diverse resource can outweigh these disadvantages by offering a more complete and/or complementary range of nutritional resources as suggested by the “balanced diet” hypothesis.
Molecular Characterization of Prdx Family and Response of Antioxidant Enzymes in Berberine Hydrochloride-Treated Charybdis japonica Infected With Aeromonas hydrophila
Authors: Han Mingming , Gao Tianheng , Liu Yuxin , Zuraini Zakaria , Zhu Chenxi , Zhang Tongqing , Ji Feng , Jiang Qichen , Sun Xian
Published: December 2021

Berberine hydrochloride is an isoquinoline alkaloid, which has antitumoral, antibacterial, and antiviral activities in vivo and in vitro. Charybdis japonica is one of the main economic species of crab in Southeast Asia. We studied the molecular mechanism of oxidative stress in berberine hydrochloride-treated C. japonica infected with Aeromonas hydrophila. C. japonica were infected with A. hydrophila after being submerged in different concentrations (0, 100, 200, and 300 mg/L) of berberine hydrochloride for 48 h. The full-length cDNA of Prx6 and the ORFs of Prx5 and PXL2A were cloned. Prx6 and PXL2A each have one conserved domain, Cys44, and Cys81. The Prx5 conserved domain contains three important Cys loci, Cys75, Cys100, and Cys76. Prx6 was different from Prx5 and PXL2A in the Peroxiredoxin family. The transcription levels of PXL2A infected with A. hydrophila were all higher than the control. The transcription levels of C. japonica were further increased by adding berberine hydrochloride and were increased the highest at a concentration of 300 mg/L. The activities of glutathione peroxidase, superoxide dismutase, and catalase in the hepatopancreas of berberine hydrochloride-treated C. japonica infected with A. hydrophila were significantly increased compared with those only infected with A. hydrophila and the control group. The glutathione transferase activity in the hepatopancreas was significantly increased in berberine hydrochloride-treated C. japonica. The results of this study provide a new understanding of the potential role of berberine hydrochloride on the oxidative stress mechanisms of C. japonica.
Development of an Elongated Ellipsoid Heat Source Model to Reduce Computation Time for Directed Energy Deposition Process
Authors: Nain Vaibhav , Engel Thierry , Carin Muriel , Boisselier Didier , Seguy Lucas
Published: December 2021

Directed Energy Deposition (DED) Additive Manufacturing process for metallic parts are becoming increasingly popular and widely accepted due to their potential of fabricating parts of large dimensions. The complex thermal cycles obtained due to the process physics results in accumulation of residual stress and distortion. However, to accurately model metal deposition heat transfer for large parts, numerical model leads to impractical computation time. In this work, a 3D transient finite element model with Quiet/Active element activation is developed for modeling metal deposition heat transfer analysis of DED process. To accurately model moving heat source, Goldak’s double ellipsoid model is implemented with small enough simulation time increment such that laser moves a distance of its radius over the course of each increment. Considering thin build-wall of Stainless Steel 316L fabricated with different process parameters, numerical results obtained with COMSOL 5.6 Multi-Physics software are successfully validated with experiment temperature data recorded at the substrate during the fabrication of 20 layers. To reduce the computation time, elongated ellipsoid heat input model that averages the heat source over its entire path is implemented. It has been found that by taking such large time increments, numerical model gives inaccurate results. Therefore, the track is divided into several sub-tracks, each of which is applied in one simulation increment. In this work, an investigation is done to find out the correct simulation time increment or sub-track size that leads to reduction in computation time (5–10 times) but still yields sufficiently accurate results (below 10% of relative error on temperature). Also, a Correction factor is introduced that further reduces computation error of elongated heat source. Finally, a new correlation is also established in finding out the correct time increment size and correction factor value to reduce the computation time yielding accurate results.
Clinical and Epidemiological Characteristics of Streptococcus suis Infections in Catalonia, Spain
Authors: Díez de los Ríos Javier , Reynaga Esteban , García-Gonzàlez Merce , Càmara Jordi , Ardanuy Carmen , Cuquet Jordi , Quesada Maria D. , Navarro Marian , Vilamala Anna , Párraga-Niño Noemi , Quero Sara , Romero Alba , Benítez Rosa M. , Altimiras Jacint , Pedro-Botet Maria Luisa
Published: December 2021

Introduction:Streptococcus suis (S. suis) is a human zoonotic pathogen of occupational origin, with infection acquired through contact with live pigs or pig meat. Pig farming is one of Catalonia's biggest industries and as a result this region of Spain has one of the highest density pig populations per km2. The aim of our study was to describe the infections caused by S. suis occurring in that area over a 9-year period.

Materials and Methods: A retrospective, multi-center study was carried out by searching records from 15 hospitals in Catalonia for the period between 2010 and 2019.

Results: Over the study period altogether nine cases of S. suis infection were identified in five hospitals, with five of these cases occurring in the 2018–2019 period. The mean age of patients was 48 ± 8.9 years and all of them were males. Five patients (55.6%) worked in pig farms. The most frequent manifestation of infection was meningitis (5 cases; 55.6%) followed by septic arthritis (3 cases; 33.3%). None of the patients died at 30 days; nonetheless, 4 developed hearing loss as a long-term complication.

Conclusion: The most commonly identified S. suis infection was meningitis. Over 50% of the episodes occurred in the last 2 years and have affected pig farm workers. Further surveillance is needed in order to know its prevalence.
Neuropsychiatric Profile as a Predictor of Cognitive Decline in Mild Cognitive Impairment
Authors: Roberto Natalia , Portella Maria J. , Marquié Marta , Alegret Montserrat , Hernández Isabel , Mauleón Ana , Rosende-Roca Maitee , Abdelnour Carla , Esteban de Antonio Ester , Tartari Juan P. , Vargas Liliana , López-Cuevas Rogelio , Bojaryn Urszula , Espinosa Ana , Ortega Gemma , Pérez-Cordón Alba , Sanabria Ángela , Orellana Adelina , de Rojas Itziar , Moreno-Grau Sonia , Montrreal Laura , Alarcón-Martín Emilio , Ruíz Agustín , Tárraga Lluís , Boada Mercè , Valero Sergi
Published: December 2021

Introduction: Mild cognitive impairment is often associated with affective and other neuropsychiatric symptoms (NPS). This co-occurrence might have a relevant impact on disease progression, from MCI to dementia.

Objective: The aim of this study was to explore the trajectories of cognitive decline in an MCI sample from a memory clinic, taking into consideration a perspective of isolated cognitive functions and based on NPS clusters, accounting for the different comorbid symptoms collected at their baseline visit.

Methods: A total of 2,137 MCI patients were monitored over a 2.4-year period. Four clusters of NPS (i.e., Irritability, Apathy, Anxiety/Depression and Asymptomatic) were used to run linear mixed models to explore the interaction of cluster with time on cognitive trajectories using a comprehensive neuropsychological battery (NBACE) administered at baseline and at the three subsequent follow-ups.

Results: A significant interaction between cluster and time in cognitive decline was found when verbal learning and cued-recall were explored (p = 0.002 for both memory functions). For verbal learning, the Irritability cluster had the largest effect size (0.69), whereas the Asymptomatic cluster showed the smallest effect size (0.22). For cued-recall, the Irritability cluster had the largest effect size among groups (0.64), and Anxiety/Depression had the smallest effect size (0.21).

Conclusions: In MCI patients, the Irritability and Apathy NPS clusters shared similar patterns of worsening in memory functioning, which could point to these NPS as risk factors of a faster cognitive decline, acting as early prognostic markers and helping in the diagnostic process.
Bidirectional Association Between Sleep and Brain Atrophy in Aging
Authors: Kokošová Viktória , Filip Pavel , Kec David , Baláž Marek
Published: December 2021

Human brain aging is characterized by the gradual deterioration of its function and structure, affected by the interplay of a multitude of causal factors. The sleep, a periodically repeating state of reversible unconsciousness characterized by distinct electrical brain activity, is crucial for maintaining brain homeostasis. Indeed, insufficient sleep was associated with accelerated brain atrophy and impaired brain functional connectivity. Concurrently, alteration of sleep-related transient electrical events in senescence was correlated with structural and functional deterioration of brain regions responsible for their generation, implying the interconnectedness of sleep and brain structure. This review discusses currently available data on the link between human brain aging and sleep derived from various neuroimaging and neurophysiological methods. We advocate the notion of a mutual relationship between the sleep structure and age-related alterations of functional and structural brain integrity, pointing out the position of high-quality sleep as a potent preventive factor of early brain aging and neurodegeneration. However, further studies are needed to reveal the causality of the relationship between sleep and brain aging.
TReMo+: Modeling Ternary and Binary ReRAM-Based Memories With Flexible Write-Verification Mechanisms
Authors: Hosseinzadeh Shima , Biglari Mehrdad , Fey Dietmar
Published: December 2021

Non-volatile memory (NVM) technologies offer a number of advantages over conventional memory technologies such as SRAM and DRAM. These include a smaller area requirement, a lower energy requirement for reading and partly for writing, too, and, of course, the non-volatility and especially the qualitative advantage of multi-bit capability. It is expected that memristors based on resistive random access memories (ReRAMs), phase-change memories, or spin-transfer torque random access memories will replace conventional memory technologies in certain areas or complement them in hybrid solutions. To support the design of systems that use NVMs, there is still research to be done on the modeling side of NVMs. In this paper, we focus on multi-bit ternary memories in particular. Ternary NVMs allow the implementation of extremely memory-efficient ternary weights in neural networks, which have sufficiently high accuracy in interference, or they are part of carry-free fast ternary adders. Furthermore, we lay a focus on the technology side of memristive ReRAMs. In this paper, a novel memory model in the circuit level is presented to support the design of systems that profit from ternary data representations. This model considers two read methods of ternary ReRAMs, namely, serial read and parallel read. They are extensively studied and compared in this work, as well as the write-verification method that is often used in NVMs to reduce the device stress and to increase the endurance. In addition, a comprehensive tool for the ternary model was developed, which is capable of performing energy, performance, and area estimation for a given setup. In this work, three case studies were conducted, namely, area cost per trit, excessive parameter selection for the write-verification method, and the assessment of pulse width variation and their energy latency trade-off for the write-verification method in ReRAM.
Aromatherapy in Stroke Patients: Is it Time to Begin?
Authors: Contrada Marianna , Cerasa Antonio , Tonin Paolo , Bagetta Giacinto , Scuteri Damiana
Published: December 2021

Stroke is the second largest cause of death worldwide, causing disease with long-term consequences and considerable healthcare costs. The application of new nursing interventions aimed at reducing distressing behaviors and at increasing patient comfort is an important part of the care and, until now, there are no defined guidelines. Aromatherapy has been demonstrated to be efficient in several other neurological disorders for the treatment of somatic and emotional diseases and to promote patient health. In the management of stroke patients, aromatherapy is still in its infancy. The first evidence coming from animal models demonstrated a consistent and reliable neuroprotective effect in reducing cerebral ischemia–reperfusion injury. In the last few years, some preliminary data being to be collected in humans revealed significant influence in reducing patients’ pain and emotional distress. In this perspective study, we sought to summarize, for the first time, the main findings emerging from this new field of study, discussing the future opportunities to be translated into primary care practice.
Dexmedetomidine Alleviates Microglia-Induced Spinal Inflammation and Hyperalgesia in Neonatal Rats by Systemic Lipopolysaccharide Exposure
Authors: Wen Wen , Gong Xingrui , Cheung Hoiyin , Yang Yanyan , Cai Meihua , Zheng Jijian , Tong Xiaoping , Zhang Mazhong
Published: December 2021

Noxious stimulus and painful experience in early life can induce cognitive deficits and abnormal pain sensitivity. As a major component of the outer membrane of gram-negative bacteria, lipopolysaccharide (LPS) injection mimics clinical symptoms of bacterial infections. Spinal microglial activation and the production of pro-inflammatory cytokines have been implicated in the pathogenesis of LPS-induced hyperalgesia in neonatal rats. Dexmedetomidine (DEX) possesses potent anti-neuroinflammatory and neuroprotective properties through the inhibition of microglial activation and microglial polarization toward pro-inflammatory (M1) phenotype and has been widely used in pediatric clinical practice. However, little is known about the effects of DEX on LPS-induced spinal inflammation and hyperalgesia in neonates. Here, we investigated whether systemic LPS exposure has persistent effects on spinal inflammation and hyperalgesia in neonatal rats and explored the protective role of DEX in adverse effects caused by LPS injection. Systemic LPS injections induced acute mechanical hyperalgesia, increased levels of pro-inflammatory cytokines in serum, and short-term increased expressions of pro-inflammatory cytokines and M1 microglial markers in the spinal cord of neonatal rats. Pretreatment with DEX significantly decreased inflammation and alleviated mechanical hyperalgesia induced by LPS. The inhibition of M1 microglial polarization and microglial pro-inflammatory cytokines expression in the spinal cord may implicate its neuroprotective effect, which highlights a new therapeutic target in the treatment of infection-induced hyperalgesia in neonates and preterm infants.
Multimodal Monitoring in Large Hemispheric Infarction: Quantitative Electroencephalography Combined With Transcranial Doppler for Prognosis Prediction
Authors: Qi Yajie , Xing Yingqi , Wang Lijuan , Zhang Jie , Cao Yanting , Liu Li , Chen Ying
Published: December 2021

Background: We aimed to explore whether transcranial Doppler (TCD) combined with quantitative electroencephalography (QEEG) can improve prognosis evaluation in patients with a large hemispheric infarction (LHI) and to establish an accurate prognosis prediction model.

Methods: We prospectively assessed 90-day mortality in patients with LHI. Brain function was monitored using TCD-QEEG at the bedside of the patient.

Results: Of the 59 (55.3 ± 10.6 years; 17 men) enrolled patients, 37 (67.3%) patients died within 90 days. The Cox regression analyses revealed that the Glasgow Coma Scale (GCS) score ≤ 8 [hazard ratio (HR), 3.228; 95% CI, 1.335–7.801; p = 0.009], TCD-terminal internal carotid artery as the offending vessel (HR, 3.830; 95% CI, 1.301–11.271; p = 0.015), and QEEG-a (delta + theta)/(alpha + beta) ratio ≥ 3 (HR, 3.647; 95% CI, 1.170–11.373; p = 0.026) independently predicted survival duration. Combining these three factors yielded an area under the receiver operating characteristic curve of 0.905 and had better predictive accuracy than those of individual variables (p < 0.05).

Conclusion: TCD and QEEG complement the GCS score to create a reliable multimodal method for monitoring prognosis in patients with LHI.
Body Fat Distribution and Associated Risk of Cardiovascular Disease in Adults With Cerebral Palsy
Authors: Shin Hyun Iee , Jung Se Hee
Published: December 2021

Objective:Fat distribution has increasingly been acknowledged as a more significant health parameter than general obesity, in terms of the risk of cardiovascular disease (CVD). We aimed to investigate the regional fat distribution pattern and general body fat characteristics of adults with cerebral palsy (CP), and we explored the risk of CVD in this population.

Methods:People aged ≥20 years who were diagnosed with CP were recruited between February 2014 and November 2014. The subjects underwent a structured interview, laboratory studies, and physical examination. The amount and distribution of fat were determined directly by dual-energy X-ray absorptiometry. Laboratory analysis was performed to measure total cholesterol and triglyceride, high-density lipoprotein (HDL), low-density lipoprotein, and fasting plasma glucose levels. The Framingham risk score (FRS) was used to present the 10-year risk for having CVD, and predictors such as sex, age, total cholesterol, HDL, systolic blood pressure, treatment for hypertension, and smoking status were used to calculate the FRS.

Results:Ninety-nine adults (58 men, mean age 41.77 ± 8.95 years) with CP were included. The participants consisted of all five levels of the Gross Motor Function Classification System. The mean body mass index (BMI) was 22.52 ± 4.58 kg/m2. According to BMI criteria, 54.9% were overweight and 27.3% were obese. The fat mass index criteria revealed 10.1% excess fat and 7.6% obesity. In univariable regression analysis, age, the timing of physical function deterioration, and android fat percentage were associated with the FRS (p<0.001,p<0.001, andp= 0.007, respectively). In multiple regression analysis, the FRS was associated with age and android fat percentage, based on the following formula:“FRS=−18.549 + 0.410 ∗ Age + 0.577 ∗ Android percent fat (%) (R2=0.528)′′                                                                                                                                        (p<0.001).

Conclusions:Body fat distribution in the android area is significantly associated with future CVD risk in adults with CP.
Decreased Intrinsic Neural Timescales in Mesial Temporal Lobe Epilepsy
Authors: Wang Kefan , Zhang Xiaonan , Song Chengru , Ma Keran , Bai Man , Zheng Ruiping , Wei Yarui , Chen Jingli , Cheng Jingliang , Zhang Yong , Han Shaoqiang
Published: December 2021

It is well established that epilepsy is characterized by the destruction of the information capacity of brain network and the interference with information processing in regions outside the epileptogenic focus. However, the potential mechanism remains poorly understood. In the current study, we applied a recently proposed approach on the basis of resting-state fMRI data to measure altered local neural dynamics in mesial temporal lobe epilepsy (mTLE), which represents how long neural information is stored in a local brain area and reflect an ability of information integration. Using resting-state-fMRI data recorded from 36 subjects with mTLE and 36 healthy controls, we calculated the intrinsic neural timescales (INT) of neural signals by summing the positive magnitude of the autocorrelation of the resting-state brain activity. Compared to healthy controls, the INT values were significantly lower in patients in the right orbitofrontal cortices, right insula, and right posterior lobe of cerebellum. Whereas, we observed no statistically significant changes between patients with long- and short-term epilepsy duration or between left-mTLE and right-mTLE. Our study provides distinct insight into the brain abnormalities of mTLE from the perspective of the dynamics of the brain activity, highlighting the significant role of intrinsic timescale in understanding neurophysiological mechanisms. And we postulate that altered intrinsic timescales of neural signals in specific cortical brain areas may be the neurodynamic basis of cognitive impairment and emotional comorbidities in mTLE patients.
Stress Response and Hearing Loss Differentially Contribute to Dynamic Alterations in Hippocampal Neurogenesis and Microglial Reactivity in Mice Exposed to Acute Noise Exposure
Authors: Li Qian , Li Hong , Yao Xiuting , Wang Conghui , Liu Haiqing , Xu Dan , Yang Chenxi , Zhuang Hong , Xiao Yu , Liu Rui , Shen Sinuo , Zhou Shaoyang , Fu Chenge , Wang Yifan , Teng Gaojun , Liu Lijie
Published: December 2021

Noise-induced hearing loss (NIHL) is one of the most prevalent forms of acquired hearing loss, and it is associated with aberrant microglial status and reduced hippocampal neurogenesis; however, the nature of these associations is far from being elucidated. Beyond its direct effects on the auditory system, exposure to intense noise has previously been shown to acutely activate the stress response, which has increasingly been linked to both microglial activity and adult hippocampal neurogenesis in recent years. Given the pervasiveness of noise pollution in modern society and the important implications of either microglial activity or hippocampal neurogenesis for cognitive and emotional function, this study was designed to investigate how microglial status and hippocampal neurogenesis change over time following acoustic exposure and to analyze the possible roles of the noise exposure-induced stress response and hearing loss in these changes. To accomplish this, adult male C57BL/6J mice were randomly assigned to either a control or noise exposure (NE) group. Auditory function was assessed by measuring ABR thresholds at 20 days post noise exposure. The time-course profile of serum corticosterone levels, microglial status, and hippocampal neurogenesis during the 28 days following noise exposure were quantified by ELISA or immunofluorescence staining. Our results illustrated a permanent moderate-to-severe degree of hearing loss, an early but transient increase in serum corticosterone levels, and time-dependent dynamic alterations in microglial activation status and hippocampal neurogenesis, which both present an early but transient change and a late but enduring change. These findings provide evidence that both the stress response and hearing loss contribute to the dynamic alterations of microglia and hippocampal neurogenesis following noise exposure; moreover, noise-induced permanent hearing loss rather than noise-induced transient stress is more likely to be responsible for perpetuating the neurodegenerative process associated with many neurological diseases.
Cerebellar Patterning Defects in Mutant Mice
Authors: Hawkes Richard
Published: December 2021

The cerebellar cortex is highly compartmentalized and serves as a remarkable model for pattern formation throughout the brain. In brief, the adult cerebellar cortex is subdivided into five anteroposterior units—transverse zones—and subsequently, each zone is divided into ∼20 parasagittal stripes. Zone-and-stripe pattern formation involves the interplay of two parallel developmental pathways—one for inhibitory neurons, the second for excitatory. In the inhibitory pathway, progenitor cells of the 4th ventricle generate the Purkinje cells and inhibitory interneurons. In the excitatory pathway, progenitor cells in the upper rhombic lip give rise to the external granular layer, and subsequently to the granular layer of the adult. Both the excitatory and inhibitory developmental pathways are spatially patterned and the interactions of the two generate the complex topography of the adult. This review briefly describes the cellular and molecular mechanisms that underly zone-and-stripe development with a particular focus on mutations known to interfere with normal cerebellar development and the light they cast on the mechanisms of pattern formation.
Frontal Cortex Segmentation of Brain PET Imaging Using Deep Neural Networks
Authors: Zhan Qianyi , Liu Yuanyuan , Liu Yuan , Hu Wei
Published: December 2021

18F-FDG positron emission tomography (PET) imaging of brain glucose use and amyloid accumulation is a research criteria for Alzheimer's disease (AD) diagnosis. Several PET studies have shown widespread metabolic deficits in the frontal cortex for AD patients. Therefore, studying frontal cortex changes is of great importance for AD research. This paper aims to segment frontal cortex from brain PET imaging using deep neural networks. The learning framework called Frontal cortex Segmentation model of brain PET imaging (FSPET) is proposed to tackle this problem. It combines the anatomical prior to frontal cortex into the segmentation model, which is based on conditional generative adversarial network and convolutional auto-encoder. The FSPET method is evaluated on a dataset of 30 brain PET imaging with ground truth annotated by a radiologist. Results that outperform other baselines demonstrate the effectiveness of the FSPET framework.
Bulk and Single-Cell Profiling of Breast Tumors Identifies TREM-1 as a Dominant Immune Suppressive Marker Associated With Poor Outcomes
Authors: Pullikuth Ashok K. , Routh Eric D. , Zimmerman Kip D. , Chifman Julia , Chou Jeff W. , Soike Michael H. , Jin Guangxu , Su Jing , Song Qianqian , Black Michael A. , Print Cristin , Bedognetti Davide , Howard-McNatt Marissa , O’Neill Stacey S. , Thomas Alexandra , Langefeld Carl D. , Sigalov Alexander B. , Lu Yong , Miller Lance D.
Published: December 2021

Background

Triggering receptor expressed on myeloid cells (TREM)-1 is a key mediator of innate immunity previously associated with the severity of inflammatory disorders, and more recently, the inferior survival of lung and liver cancer patients. Here, we investigated the prognostic impact and immunological correlates of TREM1 expression in breast tumors.

Methods

Breast tumor microarray and RNAseq expression profiles (n=4,364 tumors) were analyzed for associations between gene expression, tumor immune subtypes, distant metastasis-free survival (DMFS) and clinical response to neoadjuvant chemotherapy (NAC). Single-cell (sc)RNAseq was performed using the 10X Genomics platform. Statistical associations were assessed by logistic regression, Cox regression, Kaplan-Meier analysis, Spearman correlation, Student’s t-test and Chi-square test.

Results

In pre-treatment biopsies, TREM1 and known TREM-1 inducible cytokines (IL1B, IL8) were discovered by a statistical ranking procedure as top genes for which high expression was associated with reduced response to NAC, but only in the context of immunologically “hot” tumors otherwise associated with a high NAC response rate. In surgical specimens, TREM1 expression varied among tumor molecular subtypes, with highest expression in the more aggressive subtypes (Basal-like, HER2-E). High TREM1 significantly and reproducibly associated with inferior distant metastasis-free survival (DMFS), independent of conventional prognostic markers. Notably, the association between high TREM1 and inferior DMFS was most prominent in the subset of immunogenic tumors that exhibited the immunologically hot phenotype and otherwise associated with superior DMFS. Further observations from bulk and single-cell RNAseq analyses indicated that TREM1 expression was significantly enriched in polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) and M2-like macrophages, and correlated with downstream transcriptional targets of TREM-1 (IL8, IL-1B, IL6, MCP-1, SPP1, IL1RN, INHBA) which have been previously associated with pro-tumorigenic and immunosuppressive functions.

Conclusions

Together, these findings indicate that increased TREM1 expression is prognostic of inferior breast cancer outcomes and may contribute to myeloid-mediated breast cancer progression and immune suppression.
A Combination of Cabozantinib and Radiation Does Not Lead to an Improved Growth Control of Tumors in a Preclinical 4T1 Breast Cancer Model
Authors: Reppingen Norman , Helm Alexander , Doleschal Laura , Durante Marco , Fournier Claudia
Published: December 2021

The tyrosine kinase inhibitor Cabozantinib has been applied in clinical studies in combination with radiotherapy. We investigated the effect of such combination on triple-negative 4T1 cells as a metastatic breast cancer model in vitro and in vivo upon inoculation in BALB/c mice. In vitro assays indicated a potential for improved effects using the combination. Both Cabozantinib (2.5 µM) and 10 Gy of 250 kV x-rays were able to cease the growth of 4T1 cells as revealed by growth curves. In a clonogenic survival assay, the effect of Cabozantinib added on the effects of irradiation and the effectiveness of inhibiting the clonogenic survival was found to be 2 (RBE10). Additionally, cell death measurements of apoptosis plus necrosis revealed a synergistic effect when combining irradiation with Cabozantinib. Surprisingly, however, in vivo tumor growth kinetics showed no additional effect in growth control when irradiation was used together with Cabozantinib. Since both ionizing radiation and Cabozantinib are acknowledged to feature immunogenic effects, we additionally investigated the effect of the treatments on lung metastases. No difference to the control groups was found here, neither for irradiation nor Cabozantinib alone nor in combination. Yet, upon analysis of the mice’ livers, CD11b-positive cells, indicating immune suppressive myeloid derived suppressor cells were found diminished following treatment with Cabozantinib. In conclusion, despite promising in vitro controls of the combination of Cabozantinib and irradiation, tumor growth control was not increased by the combination, which was true also for the occurrence of lung metastases.
Modifications of Grapevine Berry Composition Induced by Main Viral and Fungal Pathogens in a Climate Change Scenario
Authors: Rienth Markus , Vigneron Nicolas , Walker Robert P. , Castellarin Simone Diego , Sweetman Crystal , Burbidge Crista A. , Bonghi Claudio , Famiani Franco , Darriet Philippe
Published: December 2021

The grapevine is subject to high number of fungal and viral diseases, which are responsible for important economic losses in the global wine sector every year. These pathogens deteriorate grapevine berry quality either directlyviathe modulation of fruit metabolic pathways and the production of endogenous compounds associated with bad taste and/or flavor, or indirectlyviatheir impact on vine physiology. The most common and devastating fungal diseases in viticulture are gray mold, downy mildew (DM), and powdery mildew (PM), caused, respectively byBotrytis cinerea,Plasmopara viticola, andErysiphe necator. WhereasB. cinereamainly infects and deteriorates the ripening fruit directly, deteriorations by DM and PM are mostly indirectviaa reduction of photosynthetic leaf area. Nevertheless, mildews can also infect berries at certain developmental stages and directly alter fruit qualityviathe biosynthesis of unpleasant flavor compounds that impair ultimate wine quality. The grapevine is furthermore host of a wide range of viruses that reduce vine longevity, productivity and berry quality in different ways. The most widespread virus-related diseases, that are known nowadays, are Grapevine Leafroll Disease (GLRD), Grapevine Fanleaf Disease (GFLD), and the more recently characterized grapevine red blotch disease (GRBD). Future climatic conditions are creating a more favorable environment for the proliferation of most virus-insect vectors, so the spread of virus-related diseases is expected to increase in most wine-growing regions. However, the impact of climate change on the evolution of fungal disease pressure will be variable and depending on region and pathogen, with mildews remaining certainly the major phytosanitary threat in most regions because their development rate is to a large extent temperature-driven. This paper aims to provide a review of published literature on most important grapevine fungal and viral pathogens and their impact on grape berry physiology and quality. Our overview of the published literature highlights gaps in our understanding of plant-pathogen interactions, which are valuable for conceiving future research programs dealing with the different pathogens and their impacts on grapevine berry quality and metabolism.
Financial Difficulties Correlate With Mental Health Among Bangladeshi Residents Amid COVID-19 Pandemic: Findings From a Cross-Sectional Survey
Authors: Siddique Abu Bakkar , Nath Sudipto Deb , Islam Md. Saiful , Khan Tausif Hasan , Pardhan Shahina , Amin M. Ziaul , Amin M. Imran Al , Shawon Zayed Bin Zakir , Koly Kamrun Nahar
Published: December 2021

Background:The COVID-19 pandemic is a global threat which has challenged mental resilience and impacted the psychological well-being of people across all age groups globally. The present study aimed to investigate how financial difficulties during the pandemic correlate with mental health among residents of Bangladesh.

Methods:A cross-sectional survey was conducted on 4,020 residents from different parts of Bangladesh between July and September 2020, during a period of elevated risk of COVID-19 infection. A self-reported online questionnaire comprising socio-demographic, financial difficulties and psychometric measures (to assess depression, anxiety and stress) was used to gather information from participants. Multivariable logistic regression analysis was performed to determine the factors associated with mental health consequences.

Results:The prevalence of depression, anxiety, and stress in the sample were 71.1%, 62.3%, and 56.7%, respectively. Levels of depression, anxiety, and stress were significantly higher among participants who reported female sex, being unmarried, smaller families, higher monthly family income, poor self-perceived health status, living near people who had been infected by COVID-19, probability of decreased income, food scarcity (both during the pandemic and in the future) and the possibility of unemployment. However, due to the nature of the cross-sectional study performed with a convenience sampling method, the causal relationship between variables cannot be justified.

Conclusions:After several months of the COVID-19 pandemic in Bangladesh, more than half of the respondents rated their mental health concerns as moderate to severe. The findings highlight the contributing factors of poor mental health which warrant the creation of interventions that address the economic, financial and mental health impacts of the pandemic.
Reliability of HOME FAST BRAZIL—Self-Reported Version for Community-Dwelling Older Adults
Authors: Ferreira Karina Stella Aoki , Gallo da Silva Tamires Terezinha , Melo Filho Jarbas , Bazanella Natacha Verônica , Vojciechowski Audrin Said , Mackenzie Lynette , Gomes Anna Raquel Silveira
Published: December 2021

Objective: Verify the intra- and inter-rater reliability of the HOME FAST BRAZIL—Self-reported version and correlate household environmental risks with the history of falls by community-dwelling older adults.

Method: Cross sectional study with 50 community-dwelling older adults who were screened by the cut-off point of the Mini Mental State Exam and replied to the HOME FAST BRAZIL—Self-reported version using two evaluators, on three occasions. The reliability analysis was determined by the Intra-class Correlation Coefficient (ICC), considering ICC > 0.70 as adequate. To test the correlations, the Spearman test was used.

Results: The mean age of the participants was 73.2 ± 5.8 years. The inter- rater reliability of HOME FAST BRAZIL—Self-reported version was ICC 0.83 (IC95%, 0.70–0.90) and the Intra- reliability ICC 0.85 (IC95%, 0.74–0.91). A risk of falls was verified in 88% of the sample and four environmental risks presented significant correlations with the history of falls.

Conclusions: The HOME FAST BRAZIL—Self-reported version presented adequate reliability for the evaluation of household environmental risks for community-dwelling older adults. Risks such as inadequate armchairs/ sofas, the absence of anti-slip mats in the shower recess, the presence of pets and inadequate beds require attention in the evaluation of household risks, due to their correlation with the occurrence of falls.
Perioperative Morbidity and Complications in Patients With an Established Ileostomy Undergoing Major Abdominal Surgery: A Retrospective Study
Authors: Uribe Alberto A. , Weaver Tristan E. , Echeverria-Villalobos Marco , Periel Luis , Shi Haixia , Fiorda-Diaz Juan , Gonzalez-Zacarias Alicia , Abdel-Rasoul Mahmoud , Li Lin
Published: December 2021

Background:Recently formed ileostomies may produce an average of 1,200 ml of watery stool per day, while an established ileostomy output varies between 600–800 ml per day. The reported incidence of renal impartment in patients with ileostomy is 8–20%, which could be caused by dehydration (up to 50%) or high output stoma (up to 40%). There is a lack of evidence if an ileostomy could influence perioperative fluid management and/or surgical outcomes.

Methods:Subjects aged ≥18 years old with an established ileostomy scheduled to undergo an elective non-ileostomy-related major abdominal surgery under general anesthesia lasting more than 2 h and requiring hospitalization were included in the study. The primary outcome was to assess the incidence of perioperative complications within 30 days after surgery.

Results:A total of 552 potential subjects who underwent non-ileostomy-related abdominal surgery were screened, but only 12 were included in the statistical analysis. In our study cohort, 66.7% of the subjects were men and the median age was 56 years old (interquartile range [IQR] 48-59). The median time from the creation of ileostomy to the qualifying surgery was 17.7 months (IQR: 8.3, 32.6). The most prevalent comorbidities in the study group were psychiatric disorders (58.3%), hypertension (50%), and cardiovascular disease (41.7%). The most predominant surgical approach was open (8 [67%]). The median surgical and anesthesia length was 3.4 h (IQR: 2.5, 5.7) and 4 h (IQR: 3, 6.5), respectively. The median post-anesthesia care unit (PACU) stay was 2 h (IQR:0.9, 3.1), while the median length of hospital stay (LOS) was 5.6 days (IQR: 4.1, 10.6). The overall incidence of postoperative complications was 50% (n= 6). Two subjects (16.7%) had a moderate surgical wound infection, and two subjects (16.7%) experienced a mild surgical wound infection. In addition, one subject (7.6%) developed a major postoperative complication with atrial fibrillation in conjunction with moderate hemorrhage.

Conclusions:Our findings suggest that the presence of a well-established ileostomy might not represent a relevant risk factor for significant perioperative complications related to fluid management or hospital readmission. However, the presence of peristomal skin complications could trigger a higher incidence of surgical wound infections.