bluuebunny/crossref_metadata_2025 huggingface dataset:
Challenges of Research on Person-Centered Care in General Practice: A Scoping Review
Authors: Burgers Jako S. , van der Weijden Trudy , Bischoff Erik W. M. A.
Published: June 2021

Background: Delivering person-centered care is one of the core values in general practice. Due to the complexity and multifaceted character of person-centered care, the effects of person-centered care cannot be easily underpinned with robust scientific evidence. In this scoping review we provide an overview of research on effects of person-centered care, exploring the concepts and definitions used, the type of interventions studied, the selected outcome measures, and its strengths and limitations.

Methods: Systematic reviews on person-centered care compared to usual care were included from Pubmed, Embase, and PsycINFO. The search was conducted in February 2021. Data selection and charting was done by two reviewers.

Results: The literature search yielded 481 articles. A total of 21 full-text articles were assessed for eligibility for inclusion. Four systematic reviews, published between 2012 and 2018, were finally included in this review. All reviews used different definitions and models and classified the interventions differently. The explicit distinction between interventions for providers and patients was made in two systematic reviews. The classification of outcomes also showed large differences, except patient satisfaction that was shared. All reviews described the results narratively. One review also pooled the results on some outcome measures. Most studies included in the reviews showed positive effects, in particular on process outcomes. Mixed results were found on patient satisfaction and clinical or health outcomes. All review authors acknowledged limitations due to lack of uniform definitions, and heterogeneity of interventions and outcomes measures.

Discussion: Person-centered care is a concept that seems obvious and understandable in real life but is complex to operationalize in research. This scoping review reinforces the need to use mixed qualitative and quantitative methods in general practice research. For spreading and scaling up person-centered care, an implementation or complexity science approach could be used. Research could be personalized by defining therapeutic goals, interventions, and outcome variables based on individual preferences, goals, and values and not only on clinical and biological characteristics. Observational data and patient satisfaction surveys could be used to support quality improvement. Integrating research, education, and practice could strengthen the profession, building on the fundament of shared core values.
Retinal Involvement in COVID-19: Results From a Prospective Retina Screening Program in the Acute and Convalescent Phase
Authors: Bansal Reema , Markan Ashish , Gautam Nitin , Guru Rashmi Ranjan , Lakshmi P. V. M. , Katoch Deeksha , Agarwal Aniruddha , Singh Mini P. , Suri Vikas , Mohindra Ritin , Sahni Neeru , Bhalla Ashish , Malhotra Pankaj , Gupta Vishali , Puri G. D.
Published: June 2021

Objective: To detect retinal involvement in coronavirus disease 2019 (COVID-19) patients in acute and convalescent phase by their fundus screening.

Methods: In a prospective, cross-sectional, observational study (July–November 2020), 235 patients (142 acute and 93 convalescent phase) underwent fundus screening in a tertiary care center in North India. For convalescent phase, “hospitalized” patients (73) were screened at least 2 weeks after hospital discharge, and “home-isolated” patients (20) were screened 17 days after symptom onset/COVID-19 testing.

Results: None in acute phase showed any retinal lesion that could be attributed exclusively to COVID-19. Five patients (5.38%) in convalescent phase had cotton wool spots (CWSs) with/without retinal hemorrhage, with no other retinal finding, and no visual symptoms, seen at a median of 30 days from COVID-19 diagnosis.

Conclusions: CWSs (and retinal hemorrhages) were an incidental finding in COVID-19, detected only in the convalescent phase. These patients were much older (median age = 69 years) than the average age of our sample and had systemic comorbidities (diabetes mellitus, hypertension, etc.). We propose the term “COVID-19 retinopathy” to denote the presence of CWSs at the posterior pole, occasionally associated with intraretinal hemorrhages, in the absence of ocular inflammation in patients with a history of COVID-19 disease.
A Continuous Battle for Host-Derived Glycans Between a Mucus Specialist and a Glycan Generalist in vitro and in vivo
Authors: Kostopoulos Ioannis , Aalvink Steven , Kovatcheva-Datchary Petia , Nijsse Bart , Bäckhed Fredrik , Knol Jan , de Vos Willem M. , Belzer Clara
Published: June 2021

The human gastrointestinal tract is colonized by a diverse microbial community, which plays a crucial role in human health. In the gut, a protective mucus layer that consists of glycan structures separates the bacteria from the host epithelial cells. These host-derived glycans are utilized by bacteria that have adapted to this specific compound in the gastrointestinal tract. Our study investigated the close interaction between two distinct gut microbiota members known to use mucus glycans, the generalist Bacteroides thetaiotaomicron and the specialist Akkermansia muciniphila in vitro and in vivo. The in vitro study, in which mucin was the only nutrient source, indicated that B. thetaiotaomicron significantly upregulated genes coding for Glycoside Hydrolases (GHs) and mucin degradation activity when cultured in the presence of A. muciniphila. Furthermore, B. thetaiotaomicron significantly upregulated the expression of a gene encoding for membrane attack complex/perforin (MACPF) domain in co-culture. The transcriptome analysis also indicated that A. muciniphila was less affected by the environmental changes and was able to sustain its abundance in the presence of B. thetaiotaomicron while increasing the expression of LPS core biosynthesis activity encoding genes (O-antigen ligase, Lipid A and Glycosyl transferases) as well as ABC transporters. Using germ-free mice colonized with B. thetaiotaomicron and/or A. muciniphila, we observed a more general glycan degrading profile in B. thetaiotaomicron while the expression profile of A. muciniphila was not significantly affected when colonizing together, indicating that two different nutritional niches were established in mice gut. Thus, our results indicate that a mucin degrading generalist adapts to its changing environment, depending on available carbohydrates while a mucin degrading specialist adapts by coping with competing microorganism through upregulation of defense related genes.
Streptococcus mutans Lacking sufCDSUB Is Viable, but Displays Major Defects in Growth, Stress Tolerance Responses and Biofilm Formation
Authors: Ellepola Kassapa , Huang Xiaochang , Riley Ryan P. , Bitoun Jacob P. , Wen Zezhang Tom
Published: June 2021

Streptococcus mutans appears to possess a sole iron-sulfur (Fe-S) cluster biosynthesis system encoded by the sufCDSUB cluster. This study was designed to examine the role of sufCDSUB in S. mutans physiology. Allelic exchange mutants deficient of the whole sufCDSUB cluster and in individual genes were constructed. Compared to the wild-type, UA159, the sufCDSUB-deficient mutant, Δsuf::kanr, had a significantly reduced growth rate, especially in medium with the absence of isoleucine, leucine or glutamate/glutamine, amino acids that require Fe-S clusters for biosynthesis and when grown with medium adjusted to pH 6.0 and under oxidative and nitrosative stress conditions. Relative to UA159, Δsuf::kanr had major defects in stress tolerance responses with reduced survival rate of > 2-logs following incubation at low pH environment or after hydrogen peroxide challenge. When compared to UA159, Δsuf::kanr tended to form aggregates in broth medium and accumulated significantly less biofilm. As shown by luciferase reporter fusion assays, the expression of sufCDSUB was elevated by > 5.4-fold when the reporter strain was transferred from iron sufficient medium to iron-limiting medium. Oxidative stress induced by methyl viologen increased sufCDSUB expression by > 2-fold, and incubation in a low pH environment led to reduction of sufCDSUB expression by > 7-fold. These results suggest that lacking of SufCDSUB in S. mutans causes major defects in various cellular processes of the deficient mutant, including growth, stress tolerance responses and biofilm formation. In addition, the viability of the deficient mutant also suggests that SUF, the sole Fe-S cluster machinery identified is non-essential in S. mutans, which is not known in any other bacterium lacking the NIF and/or ISC system. However, how the bacterium compensates the Fe-S deficiency and if any novel Fe-S assembly systems exist in this bacterium await further investigation.
Seasonal Dynamics Are the Major Driver of Microbial Diversity and Composition in Intensive Freshwater Aquaculture
Authors: Marmen Sophi , Fadeev Eduard , Al Ashhab Ashraf , Benet-Perelberg Ayana , Naor Alon , Patil Hemant J. , Cytryn Eddie , Viner-Mozzini Yehudit , Sukenik Assaf , Lalzar Maya , Sher Daniel
Published: June 2021

Aquaculture facilities such as fishponds are one of the most anthropogenically impacted freshwater ecosystems. The high fish biomass reared in aquaculture is associated with an intensive input into the water of fish-feed and fish excrements. This nutrients load may affect the microbial community in the water, which in turn can impact the fish health. To determine to what extent aquaculture practices and natural seasonal cycles affect the microbial populations, we characterized the microbiome of an inter-connected aquaculture system at monthly resolution, over 3 years. The system comprised two fishponds, where fish are grown, and an operational water reservoir in which fish are not actively stocked. Clear natural seasonal cycles of temperature and inorganic nutrients concentration, as well as recurring cyanobacterial blooms during summer, were observed in both the fishponds and the reservoir. The structure of the aquatic bacterial communities in the system, characterized using 16S rRNA sequencing, was explained primarily by the natural seasonality, whereas aquaculture-related parameters had only a minor explanatory power. However, the cyanobacterial blooms were characterized by different cyanobacterial clades dominating at each fishpond, possibly in response to distinct nitrogen and phosphate ratios. In turn, nutrient ratios may have been affected by the magnitude of fish feed input. Taken together, our results show that, even in strongly anthropogenically impacted aquatic ecosystems, the structure of bacterial communities is mainly driven by the natural seasonality, with more subtle effects of aquaculture-related factors.
Coxsackievirus A16 in Southern Vietnam
Authors: Nhu Le Nguyen Truc , Nhan Le Nguyen Thanh , Anh Nguyen To , Hong Nguyen Thi Thu , Van Hoang Minh Tu , Thanh Tran Tan , Hang Vu Thi Ty , Han Do Duong Kim , Ny Nguyen Thi Han , Nguyet Lam Anh , Quy Du Tuan , Qui Phan Tu , Khanh Truong Huu , Hung Nguyen Thanh , Tuan Ha Manh , Chau Nguyen Van Vinh , Thwaites Guy , Doorn H. Rogier van , Tan Le Van
Published: June 2021

Background: Hand, Foot and Mouth Disease (HFMD) is a major public health concern in the Asia-Pacific region. Most recent HFMD outbreaks have been caused by enterovirus A71 (EV-A71), coxsackievirus A16 (CVA16), CVA10, and CVA6. There has been no report regarding the epidemiology and genetic diversity of CVA16 in Vietnam. Such knowledge is critical to inform the development of intervention strategies.

Materials and Methods: From 2011 to 2017, clinical samples were collected from in- and outpatients enrolled in a HFMD research program conducted at three referral hospitals in Ho Chi Minh City (HCMC), Vietnam. Throat or rectal swabs positive for CVA16 with sufficient viral load were selected for whole genome sequencing and evolutionary analysis.

Results: Throughout the study period, 320 CVA16 positive samples were collected from 2808 HFMD patients (11.4%). 59.4% of patients were male. The median age was 20.8 months (IQR, 14.96–31.41). Patients resided in HCMC (55.3%), Mekong Delta (22.2%), and South East Vietnam (22.5%). 10% of CVA16 infected patients had moderately severe or severe HFMD. CVA16 positive samples from 153 patients were selected for whole genome sequencing, and 66 complete genomes were obtained. Phylogenetic analysis demonstrated that Vietnamese CVA16 strains belong to a single genogroup B1a that clusters together with isolates from China, Japan, Thailand, Malaysia, France and Australia. The CVA16 strains of the present study were circulating in Vietnam some 4 years prior to its detection in HFMD cases.

Conclusion: We report for the first time on the molecular epidemiology of CVA16 in Vietnam. Unlike EV-A71, which showed frequent replacement between subgenogroups B5 and C4 every 2–3 years in Vietnam, CVA16 displays a less pronounced genetic alternation with only subgenogroup B1a circulating in Vietnam since 2011. Our collective findings emphasize the importance of active surveillance for viral circulation in HFMD endemic countries, critical to informing outbreak response and vaccine development.
Leptothrix cholodnii Response to Nutrient Limitation
Authors: Kunoh Tatsuki , Yamamoto Tatsuya , Sugimoto Shinya , Ono Erika , Nomura Nobuhiko , Utada Andrew S.
Published: June 2021

Microorganisms are widely utilized for the treatment of wastewater in activated sludge systems. However, the uncontrolled growth of filamentous bacteria leads to bulking and adversely affects wastewater treatment efficiency. To clarify the nutrient requirements for filament formation, we track the growth of a filamentous bacterium, Leptothrix cholodnii SP-6 in different nutrient-limited conditions using a high aspect-ratio microfluidic chamber to follow cell-chain elongation and sheath formation. We find that limitations in Na+, K+, and Fe2+ yield no observable changes in the elongation of cell chains and sheath formation, whereas limitations of C, N, P, or vitamins lead to more pronounced changes in filament morphology; here we observe the appearance of partially empty filaments with wide intercellular gaps. We observe more dramatic differences when SP-6 cells are transferred to media lacking Mg2+ and Ca2+. Loss of Mg2+ results in cell autolysis, while removal of Ca2+ results in the catastrophic disintegration of the filaments. By simultaneously limiting both carbon and Ca2+ sources, we are able to stimulate planktonic cell generation. These findings paint a detailed picture of the ecophysiology of Leptothrix, which may lead to improved control over the unchecked growth of deleterious filamentous bacteria in water purification systems.
Recognition of Streptococcal Promoters by the Pneumococcal SigA Protein
Authors: Solano-Collado Virtu , Ruiz-Cruz Sofía , Lorenzo-Díaz Fabián , Pluta Radoslaw , Espinosa Manuel , Bravo Alicia
Published: June 2021

Promoter recognition by RNA polymerase is a key step in the regulation of gene expression. The bacterial RNA polymerase core enzyme is a complex of five subunits that interacts transitory with one of a set of sigma factors forming the RNA polymerase holoenzyme. The sigma factor confers promoter specificity to the RNA polymerase. In the Gram-positive pathogenic bacterium Streptococcus pneumoniae, most promoters are likely recognized by SigA, a poorly studied housekeeping sigma factor. Here we present a sequence conservation analysis and show that SigA has similar protein architecture to Escherichia coli and Bacillus subtilis homologs, namely the poorly conserved N-terminal 100 residues and well-conserved rest of the protein (domains 2, 3, and 4). Further, we have purified the native (untagged) SigA protein encoded by the pneumococcal R6 strain and reconstituted an RNA polymerase holoenzyme composed of the E. coli core enzyme and the sigma factor SigA (RNAP-SigA). By in vitro transcription, we have found that RNAP-SigA was able to recognize particular promoters, not only from the pneumococcal chromosome but also from the S. agalactiae promiscuous antibiotic-resistance plasmid pMV158. Specifically, SigA was able to direct the RNA polymerase to transcribe genes involved in replication and conjugative mobilization of plasmid pMV158. Our results point to the versatility of SigA in promoter recognition and its contribution to the promiscuity of plasmid pMV158.
The Air We Breathe: Air Pollution as a Prevalent Proinflammatory Stimulus Contributing to Neurodegeneration
Authors: Jankowska-Kieltyka Monika , Roman Adam , Nalepa Irena
Published: June 2021

Air pollution is regarded as an important risk factor for many diseases that affect a large proportion of the human population. To date, accumulating reports have noted that particulate matter (PM) is closely associated with the course of cardiopulmonary disorders. As the incidence of Alzheimer’s disease (AD), Parkinson’s disease (PD), and autoimmune disorders have risen and as the world’s population is aging, there is an increasing interest in environmental health hazards, mainly air pollution, which has been slightly overlooked as one of many plausible detrimental stimuli contributing to neurodegenerative disease onset and progression. Epidemiological studies have indicated a noticeable association between exposure to PM and neurotoxicity, which has been gradually confirmed by in vivo and in vitro studies. After entering the body directly through the olfactory epithelium or indirectly by passing through the respiratory system into the circulatory system, air pollutants are subsequently able to reach the brain. Among the potential mechanisms underlying particle-induced detrimental effects in the periphery and the central nervous system (CNS), increased oxidative stress, inflammation, mitochondrial dysfunction, microglial activation, disturbance of protein homeostasis, and ultimately, neuronal death are often postulated and concomitantly coincide with the main pathomechanisms of neurodegenerative processes. Other complementary mechanisms by which PM could mediate neurotoxicity and contribute to neurodegeneration remain unconfirmed. Furthermore, the question of how strong and proven air pollutants are as substantial adverse factors for neurodegenerative disease etiologies remains unsolved. This review highlights research advances regarding the issue of PM with an emphasis on neurodegeneration markers, symptoms, and mechanisms by which air pollutants could mediate damage in the CNS. Poor air quality and insufficient knowledge regarding its toxicity justify conducting scientific investigations to understand the biological impact of PM in the context of various types of neurodegeneration.
Defective Neuronal Positioning Correlates With Aberrant Motor Circuit Function in Zebrafish
Authors: Asante Emilia , Hummel Devynn , Gurung Suman , Kassim Yasmin M. , Al-Shakarji Noor , Palaniappan Kannappan , Sittaramane Vinoth , Chandrasekhar Anand
Published: June 2021

Precise positioning of neurons resulting from cell division and migration during development is critical for normal brain function. Disruption of neuronal migration can cause a myriad of neurological disorders. To investigate the functional consequences of defective neuronal positioning on circuit function, we studied a zebrafish frizzled3a (fzd3a) loss-of-function mutant off-limits (olt) where the facial branchiomotor (FBM) neurons fail to migrate out of their birthplace. A jaw movement assay, which measures the opening of the zebrafish jaw (gape), showed that the frequency of gape events, but not their amplitude, was decreased in olt mutants. Consistent with this, a larval feeding assay revealed decreased food intake in olt mutants, indicating that the FBM circuit in mutants generates defective functional outputs. We tested various mechanisms that could generate defective functional outputs in mutants. While fzd3a is ubiquitously expressed in neural and non-neural tissues, jaw cartilage and muscle developed normally in olt mutants, and muscle function also appeared to be unaffected. Although FBM neurons were mispositioned in olt mutants, axon pathfinding to jaw muscles was unaffected. Moreover, neuromuscular junctions established by FBM neurons on jaw muscles were similar between wildtype siblings and olt mutants. Interestingly, motor axons innervating the interhyoideus jaw muscle were frequently defasciculated in olt mutants. Furthermore, GCaMP imaging revealed that mutant FBM neurons were less active than their wildtype counterparts. These data show that aberrant positioning of FBM neurons in olt mutants is correlated with subtle defects in fasciculation and neuronal activity, potentially generating defective functional outputs.
Corticostriatal Hypermetabolism in Moyamoya Disease-Induced Hemichorea: Two Case Reports and a Literature Review
Authors: Xian Wen-biao , Zhang Xiang-song , Shi Xin-chong , Luo Gan-hua , Yi Chang , Pei Zhong
Published: June 2021

Moyamoya disease (MMD) is a rare cause of chorea, and its pathophysiological mechanism remains unclear. We explore the use of cerebral positron emission tomography (PET) to study brain functional connectivity in 2 patients with MMD-induced hemichorea. Abnormal metabolism of brain was analyzed by 18F-fluorodeoxyglucose (18F-FDG) PET images. Dopamine transporters (DAT) PET evaluated the integrity of the cerebral dopamine system. A comprehensive systemic literature search of the PubMed database was also conducted. The 18F-FDG imaging of our patients showed no responsible hypometabolism in affected brain areas, while hypermetabolism in the affected caudate nucleus, putamen and fronto-parietal areas could be seen. DAT PET imaging was normal in patient 1 (a 23-year-old woman), while remarkably reduced DAT binding was seen in the left striatum of patient 2 (a 48-year-old woman). The literature review of 9 publications revealed that 11 patients who underwent single photon emission computed tomography (SPECT) showed cerebral hypoperfusion in the cortex and subcortical area; 18F-FDG PET was performed in 3 cases, which revealed hypermetabolism in the affected striatum in 2 cases. These findings suggest that the striatal and cortical hypermetabolism in the first patient result from underactivity in indirect pathway from basal ganglia-thalamocortical circuits, causing increased activity of excitatory glutamatergic thalamostriatal and thalamocortical projection neurons. The collateral vessels in the basal ganglia might lead to disruption of normal basal ganglia signaling. A dominant left hemisphere with corpus callosal connections to the right basal ganglia resulting into left hemichorea is the most probable explanation for the second patient. We have identified abnormal functional connectivity in basal ganglia-thalamocortical circuits in patients with MMD-induced chorea highlighting the corticostriatal pathway plays an important role in the pathogenesis of MMD-induced chorea.
High-Molecular-Weight Hyaluronic Acid Vehicle Can Deliver Gadolinium Into the Cochlea at a Higher Concentration for a Longer Duration: A 9.4-T Magnetic Resonance Imaging Study
Authors: Hwang Yu-Jung , Park Mina , Park Moo Kyun , Lee Jun Ho , Oh Seung Ha , Suh Myung-Whan
Published: June 2021

Intratympanic (IT) gadolinium (Gd) injection is one method of delivering Gd into the inner ear to evaluate the amount of endolymphatic hydrops (EH) using magnetic resonance imaging (MRI). As Gd is usually prepared in a fluid form mixed with saline, Gd injected into the middle ear drains easily through the Eustachian tube within several hours. High-molecular-weight (hMW) hyaluronic acid (HA) is an ideal vehicle for IT Gd due to its viscous and adhesive properties. The present study was performed to elucidate whether novel hMW HA is superior to conventional HA in delivering Gd into the inner ear in the short term. The second aim was to verify the long-term Gd delivery efficiency of hMW HA compared to the standard-of-care vehicle (saline). IT Gd injection and 3D T1-weighted MRI were performed in 13 rats. For the short-term study (imaging after 1, 2, and 3 h), the left ear was treated with hMW HA+Gd and the right ear with conventional HA+Gd. For the long-term study (imaging after 1, 2, 3, and 4 h, 1 – 3 days, and 7 – 10 days), the left ear was treated with hMW HA+Gd and the right ear with saline+Gd. Signal intensities (SIs) in the scala tympani (ST) and scala vestibuli (SV) were quantified. Compared to conventional HA, signal enhancement was 2.3 – 2.4 times greater in the apical and middle turns after hMW HA+Gd injection (SV at 1 h). In comparison to the standard-of-care procedure, the SI was not only greater in the short term but the higher SI also lasted for a longer duration. On days 7 – 10 after IT Gd delivery, the SI in the basal turn was 1.9 – 2.1 times greater in hMW HA+Gd-treated ears than in saline IT Gd-treated ears. Overall, hMW HA may be a useful vehicle for more efficient IT Gd delivery. Gd enhancement in the cochlea improved approximately two-fold when hMW HA was used. In addition, this greater enhancement lasted for up to 7 – 10 days. Repeated MRI of EH may be possible for several days with a single IT hMW HA+Gd delivery.
Power of Hypoperfusion in Predicting Recurrent Transient Ischemic Attacks: Protocol of a Prospective Cohort Study
Authors: Wang Yue , Liang Huazheng , Jin Lingjing , Wang Shaoshi
Published: June 2021

Background: Transient ischemic attack (TIA) has a high incidence of recurrent vascular events. Hypoperfusion is one of the factors that are closely correlated with 7-day recurrence of TIA. This study aimed to evaluate the power of hypoperfusion shown on magnetic resonance (MR) perfusion imaging in predicting the incidence of 7-day recurrence of ischemic events after TIA.

Methods/Design: REATTACK is a prospective multi-centered cohort study on the correlation between MR perfusion and TIA recurrence. Ninety patients aged ≥18 years with recent (<7 days after onset) clinical TIA will be continuously included. All the patients will undergo diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) assessments within 24 h after the onset of TIA. The subjects will then be divided into a PWI positive group and a PWI negative group according to the time-to-maximum of the residue function (Tmax). PWI will be repeated after 7 days and in 3 months. The primary clinical outcome will be the recurrence of TIA within 7 days after the onset of TIA. Secondary outcomes will be the recurrence of TIA in 3 months and modified Rankin scale (mRS) score. A chi-square test will be performed to compare the difference in the incidence of recurrent TIA between the two groups, and rank sum test in the mRS score. Multivariate logistic regression will be simultaneously performed to analyze the risk factors for the recurrence of TIA.

Discussion: The results of this study will confirm whether abnormal Tmax helps to identify the patients with TIA who have high risks of recurrent ischemic events. This would largely improve the prognosis of patients with TIA.

Trial Registration:www.chictr.org.cn, registration number: ChiCTR2000031863, registered on 12 April 2020.
Effects of Active Upper Limb Orthoses Using Brain–Machine Interfaces for Rehabilitation of Patients With Neurological Disorders: Protocol for a Systematic Review and Meta-Analysis
Authors: Silva Emília M. G. S. , Holanda Ledycnarf J. , Coutinho Gustavo K. B. , Andrade Fernanda S. , Nascimento Gabriel I. S. , Nagem Danilo A. P. , Valentim Ricardo A. de M. , Lindquist Ana Raquel
Published: June 2021

Introduction: The field of brain–machine interfaces (BMI) for upper limb (UL) orthoses is growing exponentially due to improvements in motor performance, quality of life, and functionality of people with neurological diseases. Considering this, we planned a systematic review to investigate the effects of BMI-controlled UL orthoses for rehabilitation of patients with neurological disorders.

Methods: This systematic review and meta-analysis protocol was elaborated according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P 2015) and Cochrane Handbook for Systematic Reviews of Interventions. A search will be conducted on Pubmed, IEEE Xplore Digital Library, Medline, and Web of Science databases without language and year restrictions, and Patents Scope, Patentlens, and Google Patents websites in English, Spanish, French, German, and Portuguese between 2011 and 2021. Two independent reviewers will include randomized controlled trials and quasi-experimental studies using BMI-controlled active UL orthoses to improve human movement. Studies must contain participants aged >18 years, diagnosed with neurological disorders, and with impaired UL movement. Three independent reviewers will conduct the same procedure for patents. Evidence quality and risk of bias will be evaluated following the Cochrane collaboration by two review authors. Meta-analysis will be conducted in case of homogeneity between groups. Otherwise, a narrative synthesis will be performed. Data will be inserted into a table containing physical description, UL orthoses control system, and effect of BMI-controlled orthoses.

Discussion: BMI-controlled orthoses can assist individuals in several routine activities and provide functional independence and sense of overcoming limitations imposed by the underlying disease. These benefits will also be associated with orthoses descriptions, safety, portability, adverse events, and tools used to assess UL motor performance in patients with neurological disorders.

PROSPERO Registration Number: CRD42020182195.
Investigation of Tactile Perception Evoked by Ridged Texture Using ERP and Non-linear Methods
Authors: Tang Wei , Zhang Meimei , Chen Guofang , Liu Rui , Peng Yuxing , Chen Si , Shi Yibing , Hu Chunai , Bai Shengjie
Published: June 2021

The triangular ridged surface can improve the grip reliability of products, but the sharp edge of triangular ridge induces sharp and uncomfortable feeling. To study the effect of edge shape (sharp, round, and flat shape) of triangular ridges on brain activity during touching, electroencephalograph (EEG) signals during tactile perception were evaluated using event-related potentials (ERP) and non-linear analysis methods. The results showed that the early component of P100 and P200, and the late component of P300 were successfully induced during perceiving the ridged texture. The edge shape features affect the electrical activity of brain during the tactile perceptions. The sharp shape feature evoked fast P100 latency and high P100 amplitude. The flat texture with complex (sharp and flat) shape feature evoked fast P200 latency, high P200 amplitude and RQA parameters. Both of the sharp shape and complex shape feature tended to evoke high peak amplitude of P300. The large-scale structures of recurrence plots (RPs) and recurrence quantification analysis (RQA) parameters can visually and quantitatively characterize the evolution regulation of the dynamic behavior of EEG system along with the tactile process. This study proved that RPs and RQA were protential methods for the feature extraction and state recognition of EEG during tactile perception of textured surface. This research contributes to optimize surface tactile characteristics on products, especially effective surface textures design for good grip.
Electroacupuncture Attenuates Anxiety-Like Behaviors in a Rat Model of Post-traumatic Stress Disorder: The Role of the Ventromedial Prefrontal Cortex
Authors: Hou Yuchao , Chen Meiyu , Wang Can , Liu Lumin , Mao Huijuan , Qu Xiaoyi , Shen Xueyong , Yu Bo , Liu Sheng
Published: June 2021

Electroacupuncture (EA) is a promising clinical approach to treating posttraumatic stress disorder (PTSD), yet the mechanisms whereby EA can alleviate anxiety and other PTSD symptoms have yet to be clarified. In the present report, rats underwent EA for 14 consecutive days following modified single prolonged stress (MSPS) exposure. These animals were then evaluated in open field and elevated plus maze tests (OFT and EPM), while Fos immunohistochemical staining was performed to assess ventromedial prefrontal cortex (vmPFC) functional activation. In addition, an extracellular recording and stimulation system was used to analyze vmPFC inputs into the ventral tegmental area (VTA) in these rats. Temporary vmPFC inactivation was further performed to assess whether this was sufficient to reverse the anxiolytic effects of EA. Overall, rats that underwent EA treatment spent more time in the central region (OFT) and the open arm (EPM) relative to MSPS model animals (P < 0.05). These MSPS model animals also exhibited significantly fewer activated Fos-positive nuclei in the vmPFC following behavioral testing, while EA was associated with a significant relative increase in c-Fos expression in this region. The transient inactivation of the vmPFC was sufficient to reverse the effects of EA treatment on anxiety-like behaviors in MSPS model rats. MSPS and SEA rats exhibiting no differences in bursting activity between baseline and vmPFC stimulation, whereas bursting activity rose relative to baseline upon ventral mPFC stimulation in EA treated and control rats. Together, these findings indicate that the vmPFC and its inputs into the VTA are functionally linked to the anxiolytic activity of EA, implicating this pathway in the EA-mediated treatment of PTSD.
Cortical Activation to Social and Mechanical Stimuli in the Infant Brain
Authors: Biondi Marisa , Hirshkowitz Amy , Stotler Jacqueline , Wilcox Teresa
Published: June 2021

From the early days of life infants distinguish between social and non-social physical entities and have different expectations for the way these two entities should move and interact. At the same time, we know very little about the cortical systems that support this early emerging ability. The goal of the current research was to assess the extent to which infant’s processing of social and non-social physical entities is mediated by distinct information processing systems in the temporal cortex. Using a cross-sectional design, infants aged 6–9 months (Experiment 1) and 11–18 months (Experiment 2) were presented with two types of events: social interaction and mechanical interaction. In the social interaction event (patterned after Hamlin et al., 2007), an entity with googly eyes, hair tufts, and an implied goal of moving up the hill was either helped up, or pushed down, a hill through the actions of another social entity. In the mechanical interaction event, the googly eyes and hair tufts were replaced with vertical black dots and a hook and clasp, and the objects moved up or down the hill via mechanical interactions. FNIRS was used to measure activation from temporal cortex while infants viewed the test events. In both age groups, viewing social and mechanical interaction events elicited different patterns of activation in the right temporal cortex, although responses were more specialized in the older age group. Activation was not obtained in these areas when the objects moved in synchrony without interacting, suggesting that the causal nature of the interaction events may be responsible, in part, to the results obtained. This is one of the few fNIRS studies that has investigated age-related patterns of cortical activation and the first to provide insight into the functional development of networks specialized for processing of social and non-social physical entities engaged in interaction events.
Hepatoprotective Effect of Lactobacillus plantarum HFY09 on Ethanol-Induced Liver Injury in Mice
Authors: Gan Yi , Tong Jin , Zhou Xianrong , Long Xingyao , Pan Yanni , Liu Weiwei , Zhao Xin
Published: June 2021

Lactobacillus plantarum is a bacterial strain that is used as a probiotic with health-promoting effects. Our study investigated the hepatoprotective effect of Lactobacillus plantarum HFY09 (LP-HFY09) in mice with ethanol-induced liver injury. The protection afforded by LP-HFY09 was evaluated by observing the morphology of hepatic tissue and measuring liver lipid indexes and function indexes, levels of anti-oxidative enzymes, and anti-inebriation enzymes, as well as oxidative metabolism-related gene expression. Gavage administration of LP-HFY09 [1 × 109 CFU/kg body weight (bw)] limited the loss of bw, alcohol damage to the liver, and maintained the normal hepatic tissue morphology. Lactobacillus plantarum HFY09 intervention in ethanol-induced mice led to decreases in serum triglyceride (TG), total cholesterol (TC), aspartic transaminase, alanine transaminase, hyaluronidase (HAase), and precollagen III (PC III), and increases in liver alcohol dehydrogenase (ADH), and acetaldehyde dehydrogenase (ALDH). Lactobacillus plantarum HFY09 assisted with alleviating inflammation by elevating the level of interleukin 10 (IL-10) and decreasing the levels of pro-inflammatory factors [IL-6, IL-1β, and tumor necrosis factor-α (TNF)-α]. Lactobacillus plantarum HFY09 significantly elevated hepatic levels of superoxide dismutase (SOD) and glutathione (GSH), and decreased liver malondialdehyde (MDA) from 3.45 to 1.64 nmol/mg protein. Lactobacillus plantarum HFY09 exhibited an overall strong regulatory effect on liver protection when compared to that of commercial Lactobacillus delbrueckii subsp. bulgaricus. The hepatoprotective effect of LP-HFY09 was reflected by the upregulated expression of peroxisome proliferator activated-receptors α, SOD1, SOD2, glutathione peroxidase (GSH-Px), nicotinamide adenine dinucleotide phosphate (NADPH), and catalase (CAT), and the downregulated expression of cyclooxygenase-1 (COX1), c-Jun N-terminal kinase (JNK), and extracellular regulated protein kinases (ERK). Administration of LP-HFY09 at a concentration of 1.0 × 109 CFU/kg bw could be a potential intervention, for people who frequently consume alcohol.
Assessment of Tongue Strength in Sarcopenia and Sarcopenic Dysphagia: A Systematic Review and Meta-Analysis
Authors: Chen Kuan-Cheng , Lee Tsung-Min , Wu Wei-Ting , Wang Tyng-Guey , Han Der-Sheng , Chang Ke-Vin
Published: June 2021

Sarcopenic dysphagia is defined as difficulty in swallowing due to sarcopenia, which may be related to weakness of the tongue muscles. This meta-analysis aimed to explore the association between tongue strength and sarcopenia and to determine whether tongue strength measurement could be a specific indicator of sarcopenic dysphagia. We conducted a systematic search of electronic databases from their inception to February 2021 for clinical studies that investigated tongue strength in participants with and without sarcopenia. The primary outcome was the weighted mean difference (WMD) and standardized mean difference (SMD) of tongue pressure between the different groups. The secondary outcome was the correlation of tongue pressure with the subcomponents that defined sarcopenia. Ten studies that involved 1,513 participants were included in the meta-analysis. Compared with those without sarcopenia, patients with sarcopenia had significantly less tongue pressure, with a WMD of −4.353 kPa (95% CI, −7.257 to −1.450) and an SMD of −0.581 (95% CI, −0.715 to −0.446). There was no significant difference in tongue pressure between patients with sarcopenic dysphagia and those with non-sarcopenic dysphagia, with a WMD of −1.262 kPa (95% CI, −8.442 to 5.918) and an SMD of −0.187 (95% CI, −1.059 to 0.686). Significant positive associations were identified between tongue pressure and grip strength and between tongue pressure and gait speed, with correlation coefficients of 0.396 (95% CI, 0.191 to 0.567) and 0.269 (95% CI, 0.015 to 0.490), respectively. Reduced tongue strength is associated with sarcopenia but is not an exclusive marker for sarcopenic dysphagia. Tongue strength correlates with the values of subcomponents that define sarcopenia. In patients with low performance of sarcopenia subcomponent, tongue pressure must be examined to diagnose subclinical dysphagia.

Protocol registration: This meta-analysis was registered on INPLASY (registration number INPLASY202120060).
Correlation Between 18F-FDG Uptake and Immune Cell Infiltration in Metastatic Brain Lesions
Authors: An Young-Sil , Kim Se-Hyuk , Roh Tae Hoon , Park So Hyun , Kim Tae-Gyu , Kim Jang-Hee
Published: June 2021

Background

The purpose of this study was to investigate the correlation between 18F-fluorodeoxyglucose (FDG) uptake and infiltrating immune cells in metastatic brain lesions.

Methods

This retrospective study included 34 patients with metastatic brain lesions who underwent brain 18F-FDG positron emission tomography (PET)/computed tomography (CT) followed by surgery. 18F-FDG uptake ratio was calculated by dividing the standardized uptake value (SUV) of the metastatic brain lesion by the contralateral normal white matter uptake value. We investigated the clinicopathological characteristics of the patients and analyzed the correlation between 18F-FDG uptake and infiltration of various immune cells. In addition, we evaluated immune-expression levels of glucose transporter 1 (GLUT1), hexokinase 2 (HK2), and Ki-67 in metastatic brain lesions.

Results

The degree of 18F-FDG uptake of metastatic brain lesions was not significantly correlated with clinical parameters. There was no significant relationship between the 18F-FDG uptake and degree of immune cell infiltration in brain metastasis. Furthermore, other markers, such as GLUT1, HK2, and Ki-67, were not correlated with degree of 18F-FDG uptake. In metastatic brain lesions that originated from breast cancer, a higher degree of 18F-FDG uptake was observed in those with high expression of CD68.

Conclusions

In metastatic brain lesions, the degree of 18F-FDG uptake was not significantly associated with infiltration of immune cells. The 18F-FDG uptake of metastatic brain lesions from breast cancer, however, might be associated with macrophage activity.
Mutant p53 and Twist1 Co-Expression Predicts Poor Prognosis and Is an Independent Prognostic Factor in Breast Cancer
Authors: Zhang Yong-Qu , Zhang Fan , Zeng Yun-Zhu , Chen Min , Huang Wen-He , Wu Jun-Dong , Chen Wei-Ling , Gao Wen-Liang , Bai Jing-Wen , Yang Rui-Qin , Zeng Huan-Cheng , Wei Xiao-Long , Zhang Guo-Jun
Published: June 2021

Purpose

The basic helix-loop-helix transcription factor (bHLH) transcription factor Twist1 plays a key role in embryonic development and tumorigenesis. p53 is a frequently mutated tumor suppressor in cancer. Both proteins play a key and significant role in breast cancer tumorigenesis. However, the regulatory mechanism and clinical significance of their co-expression in this disease remain unclear. The purpose of this study was to analyze the expression patterns of p53 and Twist1 and determine their association with patient prognosis in breast cancer. We also investigated whether their co-expression could be a potential marker for predicting patient prognosis in this disease.

Methods

Twist1 and mutant p53 expression in 408 breast cancer patient samples were evaluated by immunohistochemistry. Kaplan-Meier Plotter was used to analyze the correlation between co-expression of Twist1 and wild-type or mutant p53 and prognosis for recurrence-free survival (RFS) and overall survival (OS). Univariate analysis, multivariate analysis, and nomograms were used to explore the independent prognostic factors in disease-free survival (DFS) and OS in this cohort.

Results

Of the 408 patients enrolled, 237 (58%) had high mutant p53 expression. Two-hundred twenty patients (53.9%) stained positive for Twist1, and 188 cases were Twist1-negative. Furthermore, patients that co-expressed Twist1 and mutant p53 (T+P+) had significantly advanced-stage breast cancer [stage III, 61/89 T+P+ (68.5%) vs. 28/89 T-P- (31.5%); stage II, 63/104 T+P+ (60.6%)vs. 41/104 T-P- (39.4%)]. Co-expression was negatively related to early clinical stage (i.e., stages 0 and I; P = 0.039). T+P+ breast cancer patients also had worse DFS (95% CI = 1.217–7.499, P = 0.017) and OS (95% CI = 1.009–9.272, P = 0.048). Elevated Twist1 and mutant p53 expression predicted shorter RFS in basal-like patients. Univariate and multivariate analysis identified three variables (i.e., lymph node involvement, larger tumor, and T+P+) as independent prognostic factors for DFS. Lymph node involvement and T+P+ were also independent factors for OS in this cohort. The total risk scores and nomograms were reliable for predicting DFS and OS in breast cancer patients.

Conclusions

Our results revealed that co-expression of mutant p53 and Twist1 was associated with advanced clinical stage, triple negative breast cancer (TNBC) subtype, distant metastasis, and shorter DFS and OS in breast cancer patients. Furthermore, lymph nodes status and co-expression of Twist1 and mutant p53 were classified as independent factors for DFS and OS in this cohort. Co-evaluation of mutant p53 and Twist1 might be an appropriate tool for predicting breast cancer patient outcome.
Identification of Prognostic Signature and Gliclazide as Candidate Drugs in Lung Adenocarcinoma
Authors: Cheng Yang , Hou Kezuo , Wang Yizhe , Chen Yang , Zheng Xueying , Qi Jianfei , Yang Bowen , Tang Shiying , Han Xu , Shi Dongyao , Wang Ximing , Liu Yunpeng , Hu Xuejun , Che Xiaofang
Published: June 2021

Background

Lung adenocarcinoma (LUAD) is the most common pathological type of lung cancer, with high incidence and mortality. To improve the curative effect and prolong the survival of patients, it is necessary to find new biomarkers to accurately predict the prognosis of patients and explore new strategy to treat high-risk LUAD.

Methods

A comprehensive genome-wide profiling analysis was conducted using a retrospective pool of LUAD patient data from the previous datasets of Gene Expression Omnibus (GEO) including GSE18842, GSE19188, GSE40791 and GSE50081 and The Cancer Genome Atlas (TCGA). Differential gene analysis and Cox proportional hazard model were used to identify differentially expressed genes with survival significance as candidate prognostic genes. The Kaplan–Meier with log-rank test was used to assess survival difference. A risk score model was developed and validated using TCGA-LUAD and GSE50081. Additionally, The Connectivity Map (CMAP) was used to predict drugs for the treatment of LUAD. The anti-cancer effect and mechanism of its candidate drugs were studied in LUAD cell lines.

Results

We identified a 5-gene signature (KIF20A, KLF4, KRT6A, LIFR and RGS13). Risk Score (RS) based on 5-gene signature was significantly associated with overall survival (OS). Nomogram combining RS with clinical pathology parameters could potently predict the prognosis of patients with LUAD. Moreover, gliclazide was identified as a candidate drug for the treatment of high-RS LUAD. Finally, gliclazide was shown to induce cell cycle arrest and apoptosis in LUAD cells possibly by targeting CCNB1, CCNB2, CDK1 and AURKA.

Conclusion

This study identified a 5-gene signature that can predict the prognosis of patients with LUAD, and Gliclazide as a potential therapeutic drug for LUAD. It provides a new direction for the prognosis and treatment of patients with LUAD.