bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Ocean Acidification, Hypoxia, and Warming on the Gut Microbiota of the Thick Shell Mussel Mytilus coruscus Through 16S rRNA Gene Sequencing
Authors: Ullah Khan Fahim , Shang Yueyong , Chang Xueqing , Kong Hui , Zuberi Amina , Fang James K. H. , Liu Wei , Peng Jinxia , Zhang Xingzhi , Hu Menghong , Wang Youji
Published: September 2021

Gut microbiota play a very important role in the health of the host, such as protecting from pathogens and maintaining homeostasis. However, environmental stressors, such as ocean acidification, hypoxia, and warming can affect microbial communities by causing alteration in their structure and relative abundance and by destroying their network. The study aimed to evaluate the combined effects of low pH, low dissolved oxygen (DO) levels, and warming on gut microbiota of the mussel Mytilus coruscus. Mussels were exposed to two pH levels (8.1, 7.7), two DO levels (6, 2 mg L−1), and two temperature levels (20, 30°C) for a total of eight treatments for 30 days. The experiment results showed that ocean acidification, hypoxia, and warming affected the community structure, species richness, and diversity of gut microbiota. The most abundant phyla noted were Proteobacteria, Bacteroidetes, and Firmicutes. Principal coordinate analysis (PCoA) revealed that ocean acidification, hypoxia, and warming change microbial community structure. Low pH, low DO, and increased temperature can cause shifting of microbial communities toward pathogen dominated microbial communities. Linear discriminant analysis effect size (LEfSe) showed that the significantly enriched biomarkers in each group are significantly different at the genus level. Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) analysis revealed that the gut microbiome of the mussels is associated with many important functions, such as amino acid transport and metabolism, transcription, energy production and conservation, cell wall, membrane and envelope biogenesis, and other functions. This study highlights the complexity of interaction among pH, DO, and temperature in marine organisms and their effects on the gut microbiota and health of marine mussels.
Mechanical Behavior of Reactive Powder Concrete Made From Local Material Subjected to Axial Pressure
Authors: Ji Jing , Kang Wei , Jiang Liangqin , Li Yunhao , Ren Hongguo , Hao Sixue , He Lingjie , Lin Yubo , Yu Chenyu
Published: September 2021

In order to investigate the influence of various parameters on the compressive strength and fluidity of reactive powder concrete (RPC) made from local materials, 22 groups of RPC cubic specimens and 3 groups of RPC prism specimens were designed, and the main parameters included water to binder ratio, the ratio of silica fume to cement, the ratio of slag powder to cement, the ratio of quartz sand to cement, volume fraction of steel fiber, and steam curing time. The stress-strain curves and failure mode of RPC cubic specimens were obtained by the axial compression test. The influence of various parameters on the compressive mechanical properties and the mixture fluidity of RPC cubic specimens was analyzed. The results showed that the ultimate compressive strength (fcu) of RPC gradually decreases with the increase in the water to binder ratio; however, fcu increases with the increase in the volume fraction of steel fiber. fcu increases firstly and then decreases with the increase in the ratio of silica fume to cement, the ratio of slag powder to cement, and the ratio of quartz sand to cement, so there exists a peak point. The fluidity of RPC mixture increases with the increase in the water to binder ratio and the ratio of slag powder to cement; on the contrary, it decreases with the increase in the ratio of silica fume to cement, the ratio of quartz sand to cement, and volume fraction of steel fiber. Based on the analysis of the parameters, the optimal mix proportion of the RPC made from local materials is proposed. The constitutive model of RPC is established according to the stress-strain curves of RPC prism specimens. Finally, the relationship between compressive strength and elastic modulus of RPC made of local materials is regressed statistically.
A Convolutional Neural Network Deep Learning Model Trained on CD Ulcers Images Accurately Identifies NSAID Ulcers
Authors: Klang Eyal , Kopylov Uri , Mortensen Brynjulf , Damholt Anders , Soffer Shelly , Barash Yiftach , Konen Eli , Grinman Ana , Yehuda Reuma Margalit , Buckley Martin , Shanahan Fergus , Eliakim Rami , Ben-Horin Shomron
Published: September 2021

Background and Study Aims: Deep learning (DL) for video capsule endoscopy (VCE) is an emerging research field. It has shown high accuracy for the detection of Crohn's disease (CD) ulcers. Non-steroidal anti-inflammatory drugs (NSAIDS) are commonly used medications. In the small bowel, NSAIDs may cause a variety of gastrointestinal adverse events including NSAID-induced ulcers. These ulcers are the most important differential diagnosis for small bowel ulcers in patients evaluated for suspected CD. We evaluated a DL network that was trained using CD VCE ulcer images and evaluated its performance for NSAID ulcers.

Patients and Methods: The network was trained using CD ulcers and normal mucosa from a large image bank created from VCE of diagnosed CD patients. NSAIDs-induced enteropathy images were extracted from the prospective Bifidobacterium breve (BIf95) trial dataset. All images were acquired from studies performed using PillCam SBIII. The area under the receiver operating curve (AUC) was used as a metric. We compared the network's AUC for detecting NSAID ulcers to that of detecting CD ulcers.

Results: Overall, the CD training dataset included 17,640 CE images. The NSAIDs testing dataset included 1,605 CE images. The DL network exhibited an AUC of 0.97 (95% CI 0.97–0.98) for identifying images with NSAID mucosal ulcers. The diagnostic accuracy was similar to that obtained for CD related ulcers (AUC 0.94–0.99).

Conclusions: A network trained on VCE CD ulcers similarly identified NSAID findings. As deep learning is transforming gastrointestinal endoscopy, this result should be taken into consideration in the future design and analysis of VCE deep learning applications.
Anti-Ro/SSA Antibodies and the Autoimmune Long-QT Syndrome
Authors: Lazzerini Pietro Enea , Laghi-Pasini Franco , Boutjdir Mohamed , Capecchi Pier Leopoldo
Published: September 2021

Autoimmunity is increasingly recognized as a novel pathogenic mechanism for cardiac arrhythmias. Several arrhythmogenic autoantibodies have been identified, cross-reacting with different types of surface proteins critically involved in the cardiomyocyte electrophysiology, primarily ion channels (autoimmune cardiac channelopathies). Specifically, some of these autoantibodies can prolong the action potential duration leading to acquired long-QT syndrome (LQTS), a condition known to increase the risk of life-threatening ventricular arrhythmias, particularly Torsades de Pointes (TdP). The most investigated form of autoimmune LQTS is associated with the presence of circulating anti-Ro/SSA-antibodies, frequently found in patients with autoimmune diseases (AD), but also in a significant proportion of apparently healthy subjects of the general population. Accumulating evidence indicates that anti-Ro/SSA-antibodies can markedly delay the ventricular repolarization via a direct inhibitory cross-reaction with the extracellular pore region of the human-ether-a-go-go-related (hERG) potassium channel, resulting in a higher propensity for anti-Ro/SSA-positive subjects to develop LQTS and ventricular arrhythmias/TdP. Recent population data demonstrate that the risk of LQTS in subjects with circulating anti-Ro/SSA antibodies is significantly increased independent of a history of overt AD, intriguingly suggesting that these autoantibodies may silently contribute to a number of cases of ventricular arrhythmias and cardiac arrest in the general population. In this review, we highlight the current knowledge in this topic providing complementary basic, clinical and population health perspectives.
Marked Seasonal Variation in Structure and Function of Gut Microbiota in Forest and Alpine Musk Deer
Authors: Jiang Feng , Gao Hongmei , Qin Wen , Song Pengfei , Wang Haijing , Zhang Jingjie , Liu Daoxin , Wang Dong , Zhang Tongzuo
Published: September 2021

Musk deer (Moschus spp.) is a globally endangered species due to excessive hunting and habitat fragmentation. Captive breeding of musk deer can efficiently relieve the hunting pressure and contribute to the conservation of the wild population and musk supply. However, its effect on the gut microbiota of musk deer is unclear. Recent studies have indicated that gut microbiota is associated with host health and its environmental adaption, influenced by many factors. Herein, high-throughput sequencing of the 16S rRNA gene was used based on 262 fecal samples from forest musk deer (M. berezovskii) (FMD) and 90 samples from alpine musk deer (M. chrysogaster) (AMD). We sought to determine whether seasonal variation can affect the structure and function of gut microbiota in musk deer. The results demonstrated that FMD and AMD had higher α-diversity of gut microbiota in the cold season than in the warm season, suggesting that season change can affect gut microbiota diversity in musk deer. Principal coordinate analysis (PCoA) also revealed significant seasonal differences in the structure and function of gut microbiota in AMD and FMD. Particularly, phyla Firmicutes and Bacteroidetes significantly dominated the 352 fecal samples from captive FMD and AMD. The relative abundance of Firmicutes and the ratio of Firmicutes to Bacteroidetes were significantly decreased in summer than in spring and substantially increased in winter than in summer. In contrast, the relative abundance of Bacteroidetes showed opposite results. Furthermore, dominant bacterial genera and main metabolic functions of gut microbiota in musk deer showed significant seasonal differences. Overall, the abundance of main gut microbiota metabolic functions in FMD was significantly higher in the cold season. WGCNA analysis indicated that OTU6606, OTU5027, OTU7522, and OTU3787 were at the core of the network and significantly related with the seasonal variation. These results indicated that the structure and function in the gut microbiota of captive musk deer vary with seasons, which is beneficial to the environmental adaptation and the digestion and metabolism of food. This study provides valuable insights into the healthy captive breeding of musk deer and future reintroduction programs to recover wild populations.
Development of a Loop-Mediated Isothermal Amplification Method for the Rapid Detection of Phytopythium vexans
Authors: Wang Tuhong , Ji Haojun , Yu Yongting , Wang Xiaojie , Cheng Yi , Li Zhimin , Chen Jia , Guo Litao , Xu Jianping , Gao Chunsheng
Published: September 2021

Brown root rot caused byPhytopythium vexansis a new destructive root disease on many plants such as Gingko, Citrus, kiwifruit, and ramie. The establishment of loop-mediated isothermal amplification (LAMP) technology for detectingP. vexanscan help monitor and control brown root rot quickly, efficiently, and accurately. LAMP technology is known for its simplicity, sensitivity, and speed; and it does not require any specialized equipment – a water bath or a thermoblock is sufficient for isothermal amplifications. LAMP products can be visualized by using hydroxy naphthol blue (HNB) dye or agarose gel electrophoresis. In this study, by searching and comparing the internal transcribed spacer (ITS) sequences ofP. vexansand the related species in oomycete generaPythium, Phytopythium, andPhytophthora, we designed specific primers targeting the ITS gene region ofP. vexans. Using HNB dye, we established a LAMP technique for rapid detection ofP. vexansby visible color change. In addition, we optimized the protocol to enhance both sensitivity and specificity forP. vexansdetection. Under the optimized condition, our protocol based on LAMP technology could detect as low as 24 copies of theP. vexansgenomic DNA, which is ∼100 times more sensitive than conventional PCR. This method can successfully detectP. vexansusing cell suspensions fromP. vexans– infected ramie root tissues.
Fibril Surface-Dependent Amyloid Precursors Revealed by Coarse-Grained Molecular Dynamics Simulation
Authors: Ma Yuan-Wei , Lin Tong-You , Tsai Min-Yeh
Published: September 2021

Amyloid peptides are known to self-assemble into larger aggregates that are linked to the pathogenesis of many neurodegenerative disorders. In contrast to primary nucleation, recent experimental and theoretical studies have shown that many toxic oligomeric species are generated through secondary processes on a pre-existing fibrillar surface. Nucleation, for example, can also occur along the surface of a pre-existing fibril—secondary nucleation—as opposed to the primary one. However, explicit pathways are still not clear. In this study, we use molecular dynamics simulation to explore the free energy landscape of a free Abeta monomer binding to an existing fibrillar surface. We specifically look into several potential Abeta structural precursors that might precede some secondary events, including elongation and secondary nucleation. We find that the overall process of surface-dependent events can be described at least by the following three stages: 1. Free diffusion 2. Downhill guiding 3. Dock and lock. And we show that the outcome of adding a new monomer onto a pre-existing fibril is pathway-dependent, which leads to different secondary processes. To understand structural details, we have identified several monomeric amyloid precursors over the fibrillar surfaces and characterize their heterogeneity using a probability contact map analysis. Using the frustration analysis (a bioinformatics tool), we show that surface heterogeneity correlates with the energy frustration of specific local residues that form binding sites on the fibrillar structure. We further investigate the helical twisting of protofilaments of different sizes and observe a length dependence on the filament twisting. This work presents a comprehensive survey over the properties of fibril growth using a combination of several openMM-based platforms, including the GPU-enabled openAWSEM package for coarse-grained modeling, MDTraj for trajectory analysis, and pyEMMA for free energy calculation. This combined approach makes long-timescale simulation for aggregation systems as well as all-in-one analysis feasible. We show that this protocol allows us to explore fibril stability, surface binding affinity/heterogeneity, as well as fibrillar twisting. All these properties are important for understanding the molecular mechanism of surface-catalyzed secondary processes of fibril growth.
Role of the Extracellular Matrix in Alzheimer’s Disease
Authors: Sun Yahan , Xu Sen , Jiang Ming , Liu Xia , Yang Liang , Bai Zhantao , Yang Qinghu
Published: September 2021

Alzheimer’s disease (AD) is a neurodegenerative disease with complex pathological characteristics, whose etiology and pathogenesis are still unclear. Over the past few decades, the role of the extracellular matrix (ECM) has gained importance in neurodegenerative disease. In this review, we describe the role of the ECM in AD, focusing on the aspects of synaptic transmission, amyloid-β-plaque generation and degradation, Tau-protein production, oxidative-stress response, and inflammatory response. The function of ECM in the pathological process of AD will inform future research on the etiology and pathogenesis of AD.
Stress Granules Modulate SYK to Cause Tau-Associated Neurocognitive Deterioration in 5XFAD Mouse After Anesthesia and Surgery
Authors: Shen Yang , Zhang Tong , Zhang Yinglin , Wang Yinuo , Yao Junyan
Published: September 2021

Background

Alzheimer’s disease (AD) is the most common type of dementia. However, no curative therapy has been found effective to slow down the process of AD. It is reported that anesthesia and surgery will induce neurocognitive deterioration in AD, but the mechanism is not quite clear. In this study, we aim to compare the cognitive impairment between 5XFAD transgenic (Tg) mice and its littermate (LM) after isoflurane anesthesia and surgery to clarify the specific impacts of anesthesia and surgery on individuals with AD and to explore the mechanisms.

Methods

We performed abdominal surgery in cognitively impaired, 4-month-old female 5XFAD mice and LM control mice. Isoflurane anesthesia (1.4%) was induced and maintained over 2 h. Open field and fear conditioning tests were conducted on 1, 3 and 7 days after anesthesia and surgery. The total distance, velocity and freezing time were the major outcomes. P-tau (AT8), tau oligomers (T22), stress granules (SGs), the SYK tyrosine kinase and p-SYK in the hippocampus at postoperative day 1 were evaluated by Western Blot assays. The colocalization of SGs, SYK, p-SYK, and neurons in the hippocampus section was assessed using qualitative immunofluorescence.

Results

In the open field test, no difference between the distance moved and the velocity of LM mice and 5XFAD Tg mice were found on day 1 after anesthesia and surgery. 5XFAD Tg mice exhibited reduced freezing time of fear conditioning context test on postoperative day 3, but not on day 7; the LM mice showed no changes in FCTs. Furthermore, p-tau, tau oligomers, SGs, SYK and p-SYK were evident in the hippocampus region of 5XFAD Tg mice on a postoperative day 1. In addition, SGs, SYK, p-SYK were colocalized with hippocampus neurons, as shown by immunofluorescence.

Conclusion

This study demonstrates that anesthesia and surgery may induce tau-associated neurocognitive deterioration in individuals with AD. The mechanism under it may be associated with SGs and the tyrosine kinase, SYK. After anesthesia and surgery, in 5XFAD Tg mice, SGs were formed and SYK was phosphorylated, which may contribute to the phosphorylation of tau protein. This study provided hints that individuals with AD may be more vulnerable to anesthesia and surgery.
Glypican 4 Regulates Aβ Internalization in Neural Stem Cells Partly via Low-Density Lipoprotein Receptor-Related Protein 1
Authors: Ma Kaige , Xing Shan , Luan Yan , Zhang Chenglin , Liu Yingfei , Fei Yulang , Zhang Zhichao , Liu Yong , Chen Xinlin
Published: September 2021

Neural stem cell (NSC) damage has been reported in patients with Alzheimer’s disease. Intracellular Aβ plays a vital role in NSC damage. Heparan sulfate proteoglycans are potent mediators of Aβ enrichment in the brain. We hypothesized the heparan sulfate proteoglycan glypican 4 (Gpc4) regulates Aβ internalization by NSCs. We evaluated Gpc4 expression in NSCs from P0–P2 generations using immunofluorescence. Adenovirus and lentivirus were used to regulate Gpc4 expression in NSCs and APP/PS1 mice, respectively. Co-immunoprecipitation was used to determine the relationship between Gpc4, Aβ, and low-density lipoprotein receptor-related protein 1 (LRP1). Intracellular Aβ concentrations were detected using enzyme-linked immunosorbent assay and immunofluorescence. The role of Gpc4/LRP1 on toxic/physical Aβ-induced effects was evaluated using the JC-1 kit, terminal deoxynucleotidyl transferase dUPT nick end labeling, and western blotting. Gpc4 was stably expressed in NSCs, neurons, and astrocytes. Gpc4 was upregulated by Aβ in NSCs and regulated Aβ internalization. Gpc4 attenuation reduced Aβ uptake; Gpc4 overexpression increased Aβ uptake. Gpc4 regulated Aβ internalization through LRP1 and contributed to Aβ internalization and toxic/physical concentrations of Aβ-induced mitochondrial membrane potential and cell apoptosis, partly via LRP1. Therefore, Gpc4 is a key regulator of Aβ enrichment in NSCs. Inhibiting Gpc4 rescued the Aβ-induced toxic effect and attenuated the nontoxic Aβ enrichment into intracellular toxic concentrations. Gpc4 contributed to Aβ internalization and toxic/physical concentrations of Aβ-induced mitochondrial membrane potential damage and cell apoptosis, partly via LRP1. These findings suggest a potential role of Gpc4 in treating Alzheimer’s disease at an early stage, by targeting NSCs.
Remote Ischemic Conditioning May Improve Disability and Cognition After Acute Ischemic Stroke: A Pilot Randomized Clinical Trial
Authors: Poalelungi Alina , Tulbă Delia , Turiac Elena , Stoian Diana , Popescu Bogdan Ovidiu
Published: September 2021

Background and Aim: Remote ischemic conditioning is a procedure purported to reduce the ischemic injury of an organ. This study aimed to explore the efficiency and safety of remote ischemic conditioning in patients with acute ischemic stroke. We hypothesized that remote ischemic conditioning administered from the first day of hospital admission would improve the infarct volume and clinical outcome at 180 days.

Material and Methods: We performed a unicentric double-blind randomized controlled trial. We included all patients consecutively admitted to an Emergency Neurology Department with acute ischemic stroke, ineligible for reperfusion treatment, up to 24 hours from onset. All subjects were assigned to receive secondary stroke prevention treatment along with remote ischemic conditioning on the non-paretic upper limb during the first 5 days of hospitalization, twice daily - a blood pressure cuff placed around the arm was inflated to 20 mmHg above the systolic blood pressure (up to 180 mmHg) in the experimental group and 30 mmHg in the sham group. The primary outcome was the difference in infarct volume (measured on brain CT scan) at 180 days compared to baseline, whereas the secondary outcomes included differences in clinical scores (NIHSS, mRS, IADL, ADL) and cognitive/mood changes (MoCA, PHQ-9) at 180 days compared to baseline.

Results: We enrolled 40 patients; the mean age was 65 years and 60% were men. Subjects in the interventional group had slightly better recovery in terms of disability, as demonstrated by the differences in disability scores between admission and 6 months (e.g., the median difference score for Barthel was −10 in the sham group and −17.5 in the interventional group, for ADL −2 in the sham group and −2.5 in the interventional group), as well as cognitive performance (the median difference score for MoCA was −2 in the sham group and −3 in the interventional group), but none of these differences reached statistical significance. The severity of symptoms (median difference score for NIHSS = 5 for both groups) and depression rate (median difference score for PHQ-9 = 0 for both groups) were similar in the two groups. The median difference between baseline infarct volume and final infarct volume at 6 months was slightly larger in the sham group compared to the interventional group (p = 0.4), probably due to an initial larger infarct volume in the former.

Conclusion: Our results suggest that remote ischemic conditioning might improve disability and cognition. The difference between baseline infarct volume and final infarct volume at 180 days was slightly larger in the sham group.
Long-Term Follow-Up Results of Mechanical Wrist Traction as Non-Invasive Treatment for Carpal Tunnel Syndrome
Authors: Meems Margreet , Boekhorst Myrthe G. B. M. , Pop Victor J. M.
Published: September 2021

Background: For patients with carpal tunnel syndrome (CTS), the only long-term effective treatment option is carpal tunnel release surgery. Up to one-third report recurrent symptoms, and 12% needs repeated surgery. This study aimed to evaluate the long-term effects of mechanical traction as a non-invasive treatment option for CTS compared to care as usual.

Methods: Patients with electrodiagnostically confirmed CTS [N = 181; mean age, 58.1 (13.0) years; 67% women] were recruited from an outpatient neurology clinic in the Netherlands. Patients completed baseline questionnaires and randomized to the intervention group (12 treatments with mechanical traction, twice a week for 6 weeks) or care as usual. The primary clinical outcome measure was surgery during the 12-month follow-up. Secondly, we assessed symptom severity with the Boston Carpal Tunnel Questionnaire (BCTQ) at baseline and at the 12-month follow-up. Changes in CTS symptom severity between baseline and the 12-month follow-up were analyzed between groups using t-tests and a multiple linear regression analyses, adjusting for duration of complaints, age, gender, and symptom severity at baseline.

Results: At the 12-month follow-up, 35 of 94 (37%) patients in the intervention group had surgery, compared to 38 of 87 (44%) in the care-as-usual group (χ12 = 0.78, p = 0.377). Symptom severity and functional status scores did not significantly differ between the intervention (n = 81) and care-as-usual group (n = 55) at follow-up. For patients who did not have surgery, BCTQ scores decreased significantly more from baseline to the 12-month follow-up in the intervention group (n = 53) compared to patients in the care-as-usual group (n = 25). For patients who did not have surgery, belonging to the intervention group and a higher BCTQ score at baseline were related to a greater decrease in BCTQ scores from baseline to the 12-month follow-up, as well as symptom severity and functional status.

Conclusions: Mechanical traction is effective in reducing symptom severity compared to current conservative treatment options in standard care and can therefore benefit the large number of patients that prefer conservative treatment for CTS.

Clinical Trial Registration: Clinical Trials NL44692.008.13. Registered 19 September 2013, https://clinicaltrials.gov/ct2/show/NCT01949493
Association Between Alkaline Phosphatase and Clinical Outcomes in Patients With Spontaneous Intracerebral Hemorrhage
Authors: Li Sijia , Wang Wenjuan , Zhang Qian , Wang Yu , Wang Anxin , Zhao Xingquan
Published: September 2021

Background: Spontaneous intracerebral hemorrhage (ICH) is associated with high rates of mortality and morbidity. Alkaline phosphatase (ALP) is related to increased risk of cardiovascular events and is also closely associated with adverse outcomes after ischemic or hemorrhagic stroke. However, there are limited data about the effect of ALP on clinical outcomes after ICH. Therefore, we aimed to investigate the relationship between serum ALP level and prognosis in ICH patients.

Methods: From January 2014 to September 2016, 939 patients with spontaneous ICH were enrolled in our study from 13 hospitals in Beijing. Patients were categorized into four groups based on the ALP quartiles (Q1, Q2, Q3, Q4). The main outcomes were 30-day, 90-day, and 1-year poor functional outcomes (modified Rankin Scale score of 3–6). Multivariable logistic regression and interaction analyses were performed to evaluate the relationships between ALP and clinical outcomes after ICH.

Results: In the logistic regression analysis, compared with the third quartile of ALP, the adjusted odds ratios of the Q1, Q2, and Q4 for 30-day poor functional outcome were 1.31 (0.80–2.15), 1.16 (0.71–1.89), and 2.16 (1.32–3.55). In terms of 90-day and 1-year poor functional outcomes, the risks were significantly higher in the highest quartile of ALP compared with the third quartile after adjusting the confounding factors [90-day: highest quartile OR = 1.86 (1.12–3.10); 1-year: highest quartile OR = 2.26 (1.34–3.80)]. Moreover, there was no significant interaction between ALP and variables like age or sex.

Conclusions: High ALP level (>94.8 U/L) was independently associated with 30-day, 90-day, and 1-year poor functional outcomes in ICH patients. Serum ALP might serve as a predictor for poor functional outcomes after ICH onset.
Effectiveness of the Mobility Rehab System for Mobility Training in Older Adults: A Pragmatic Clinical Trial
Authors: Vitório Rodrigo , El-Gohary Mahmoud , Pearson Sean , Carlson-Kuhta Patricia , Harker Graham , Horak Fay B. , Lapidus Jodi , Studer Mike , Mancini Martina
Published: September 2021

Introduction: Mobility impairments are among the main causes of falls in older adults and patients with neurological diseases, leading to functional dependence and substantial health care costs. Feedback-based interventions applied in controlled, laboratory environments have shown promising results for mobility rehabilitation, enhancing the benefits of standard therapy. However, the effectiveness of sensor-based feedback to improve gait in actual outpatient physical therapy settings is unknown. The proposed trial examines the effectiveness of a physical therapist-assisted, visual feedback system using wearable inertial sensors, Mobility Rehab, for mobility training in older adults with gait disturbances in an outpatient clinic.

Methods: The study is a single site, pragmatic clinical trial in older adults with gait disturbances. Two hundred patients undergoing their outpatient rehabilitation program are assigned, by an independent assistant, for screening by one of four therapists, and assigned to either a standard physical therapy or therapist-assisted feedback therapy. Both groups train twice a week for 6 weeks. Four physical therapists were randomized and stratified by years of experience to deliver standard therapy or therapist-assisted feedback rehabilitation. Each session is 45 min long. Gait is trained for 30 min. The additional 15 min include exercises for endurance, strength, and static and dynamic balance in functional tasks. Mobility Rehab uses unobtrusive, inertial sensors on the feet and belt with real-time algorithms to provide real-time feedback on gait metrics (i.e., gait speed, double support time, foot clearance, angle at foot strike, and arm swing), which are displayed on a hand-held monitor. Blinded assessments are carried out before and after the intervention. The primary outcome measure is subjects' perception of balance as measured by the Activities-specific Balance Confidence scale. Gait speed, as measured with wearable inertial sensors during walking, is the secondary outcome measure.

Discussion: We hypothesize that therapist-assisted feedback rehabilitation will be more effective than standard rehabilitation for gait. Feedback of motor performance plays a crucial role in rehabilitation and objective characterization of gait impairments by Mobility Rehab has the potential to improve the accuracy of patient-specific gait feedback.

Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03869879.
Deep Feature Extraction for Resting-State Functional MRI by Self-Supervised Learning and Application to Schizophrenia Diagnosis
Authors: Hashimoto Yuki , Ogata Yousuke , Honda Manabu , Yamashita Yuichi
Published: September 2021

In this study, we propose a deep-learning technique for functional MRI analysis. We introduced a novel self-supervised learning scheme that is particularly useful for functional MRI wherein the subject identity is used as the teacher signal of a neural network. The neural network is trained solely based on functional MRI-scans, and the training does not require any explicit labels. The proposed method demonstrated that each temporal volume of resting state functional MRI contains enough information to identify the subject. The network learned a feature space in which the features were clustered per subject for the test data as well as for the training data; this is unlike the features extracted by conventional methods including region of interests (ROIs) pooling signals and principal component analysis. In addition, applying a simple linear classifier to the per-subject mean of the features (namely “identity feature”), we demonstrated that the extracted features could contribute to schizophrenia diagnosis. The classification accuracy of our identity features was comparable to that of the conventional functional connectivity. Our results suggested that our proposed training scheme of the neural network captured brain functioning related to the diagnosis of psychiatric disorders as well as the identity of the subject. Our results together highlight the validity of our proposed technique as a design for self-supervised learning.
Validation and Reliability of a Novel Vagus Nerve Neurodynamic Test and Its Effects on Heart Rate in Healthy Subjects: Little Differences Between Sexes
Authors: Carta Giacomo , Seregni Agnese , Casamassima Andrea , Galli Manuela , Geuna Stefano , Pagliaro Pasquale , Zago Matteo
Published: September 2021

Background

The vagus nerve (VN), also called the pneumogastric nerve, connects the brainstem to organs contained in the chest and abdomen. Physiologically, VN stimulation can rapidly affect cardiac activity and heart rate (HR). VN neuropathy can increase the risk of arrhythmias and sudden death. Therefore, a selective test of VN function may be very useful. Since peripheral neurodynamic tests (NDT) are reliable for the assessment of neuropathies in somatic nerves, we aimed to validate a novel NDT to assess VN activity, namely, the VN-NTD.

Methods

In this cross-sectional double-blind, sex-balanced study, 30 participants (15 females) completed a checklist of autonomic dysfunction symptoms. During the VN-NDT administration, HR and symptoms (i.e., mechanical allodynia) were monitored in parallel to a real-time ultrasonography imaging (USI) and motion capture analysis of the neck. The VN-NDT impact on HR and its accuracy for autonomic symptoms reported in the last 7 days were tested.

Results

The VN-NDT induced a significant HR reduction of about 12 and 8 bpm in males and females [t(1, 119) = 2.425; p < 0.017; ηp2 = 0.047, 95% confidence interval (CI): 0.93–9.18], respectively. No adverse events were observed during VN-NDT. A substantial interexaminer agreement between the evaluators in symptoms induction by VN-NDT was detected [F(1, 119) = 0.540; p = 0.464; ηp2 = 0.005, low effect]. Notably, mechanical allodynia accuracy for gastrointestinal dysfunctions was excellent (p < 0.05; 95% CI: 0.52–0.73; p < 0.001; 95% CI: 0.81–0.96).

Conclusions

The novel VN-NDT is a valid and accurate test capable of detecting VN activation with high sensitivity. Data provided are suitable for both sexes as a hallmark of HR variation due to VN normal response. The proposed VN-NDT may be reliable as daily routine neurological examination tests for the evaluation of neuropathic signs related to neuroinflammation of the VN.

Clinical Trial Registration

www.ClinicalTrials.gov, identifier NCT04192877.
What Is Our Understanding of the Influence of Gut Microbiota on the Pathophysiology of Parkinson’s Disease?
Authors: Hill Amaryllis E. , Wade-Martins Richard , Burnet Philip W. J.
Published: September 2021

Microbiota have increasingly become implicated in predisposition to human diseases, including neurodegenerative disorders such as Parkinson’s disease (PD). Traditionally, a central nervous system (CNS)-centric approach to understanding PD has predominated; however, an association of the gut with PD has existed since Parkinson himself reported the disease. The gut–brain axis refers to the bidirectional communication between the gastrointestinal tract (GIT) and the brain. Gut microbiota dysbiosis, reported in PD patients, may extend this to a microbiota–gut–brain axis. To date, mainly the bacteriome has been investigated. The change in abundance of bacterial products which accompanies dysbiosis is hypothesised to influence PD pathophysiology via multiple mechanisms which broadly centre on inflammation, a cause of alpha-synuclein (a-syn) misfolding. Two main routes are hypothesised by which gut microbiota can influence PD pathophysiology, the neural and humoral routes. The neural route involves a-syn misfolding peripherally in the enteric nerves which can then be transported to the brain via the vagus nerve. The humoral route involves transportation of bacterial products and proinflammatory cytokines from the gut via the circulation which can cause central a-syn misfolding by inducing neuroinflammation. This article will assess whether the current literature supports gut bacteria influencing PD pathophysiology via both routes.
Nervous System-Systemic Crosstalk in SARS-CoV-2/COVID-19: A Unique Dyshomeostasis Syndrome
Authors: Anand Harnadar , Ende Victoria , Singh Gurinder , Qureshi Irfan , Duong Tim Q. , Mehler Mark F.
Published: September 2021

SARS-CoV-2 infection is associated with a spectrum of acute neurological syndromes. A subset of these syndromes promotes higher in-hospital mortality than is predicted by traditional parameters defining critical care illness. This suggests that deregulation of components of the central and peripheral nervous systems compromises the interplay with systemic cellular, tissue and organ interfaces to mediate numerous atypical manifestations of COVID-19 through impairments in organismal homeostasis. This unique dyshomeostasis syndrome involves components of the ACE-2/1 lifecycles, renin-angiotensin system regulatory axes, integrated nervous system functional interactions and brain regions differentially sculpted by accelerated evolutionary processes and more primordial homeostatic functions. These biological contingencies suggest a mechanistic blueprint to define long-term neurological sequelae and systemic manifestations such as premature aging phenotypes, including organ fibrosis, tissue degeneration and cancer. Therapeutic initiatives must therefore encompass innovative combinatorial agents, including repurposing FDA-approved drugs targeting components of the autonomic nervous system and recently identified products of SARS-CoV-2-host interactions.
Study on Magnetic Control Systems of Micro-Robots
Authors: Shao Youjia , Fahmy Ashraf , Li Ming , Li Chunxu , Zhao Wencang , Sienz Johann
Published: September 2021

Magnetic control systems of micro-robots have recently blossomed as one of the most thrilling areas in the field of medical treatment. For the sake of learning how to apply relevant technologies in medical services, we systematically review pioneering works published in the past and divide magnetic control systems into three categories: stationary electromagnet control systems, permanent magnet control systems and mobile electromagnet control systems. Based on this, we ulteriorly analyze and illustrate their respective strengths and weaknesses. Furthermore, aiming at surmounting the instability of magnetic control system, we utilize SolidWorks2020 software to partially modify the SAMM system to make its final overall thickness attain 111 mm, which is capable to control and observe the motion of the micro-robot under the microscope system in an even better fashion. Ultimately, we emphasize the challenges and open problems that urgently need to be settled, and summarize the direction of development in this field, which plays a momentous role in the wide and safe application of magnetic control systems of micro-robots in clinic.
L-Serine, an Endogenous Amino Acid, Is a Potential Neuroprotective Agent for Neurological Disease and Injury
Authors: Ye Lisha , Sun Yechao , Jiang Zhenglin , Wang Guohua
Published: September 2021

Central nervous system (CNS) lesions are major causes of human death and disability worldwide, and they cause different extents of motor and sensory dysfunction in patients. Thus, it is crucial to develop new effective neuroprotective drugs and approaches targeted to the heterogeneous nature of CNS injury and disease. L-serine is an indispensable neurotrophic factor and a precursor for neurotransmitters. Although L-serine is a native amino acid supplement, its metabolic products have been shown to be essential not only for cell proliferation but also for neuronal development and specific functions in the brain. Growing evidence has suggested that L-serine regulates the release of several cytokines in the brain under some neuropathological conditions to recover cognitive function, improve cerebral blood flow, inhibit inflammation, promote remyelination and exert other neuroprotective effects on neurological injury. L-serine has also been used to treat epilepsy, schizophrenia, psychosis, and Alzheimer’s Disease as well as other neurological diseases. Furthermore, the dosing of animals with L-serine and human clinical trials investigating the therapeutic effects of L-serine generally support the safety of L-serine. The high significance of this review lies in its emphasis on the therapeutic potential of using L-serine as a general treatment for numerous CNS diseases and injuries. Because L-serine performs a broad spectrum of functions, it may be clinically used as an effective neuroprotective agent.
Antioxidant Effect of Lactobacillus fermentum CQPC04-Fermented Soy Milk on D-Galactose-Induced Oxidative Aging Mice
Authors: Zhou Xianrong , Du Hang-hang , Jiang Meiqing , Zhou Chaolekang , Deng Yuhan , Long Xingyao , Zhao Xin
Published: September 2021

The aim of this study is to evaluate the changes in soy isoflavones and peptides in soy milk after lactic acid bacterial fermentation, and explore the positive effects of fermented soy milk on an oxidative aging mouse model induced with D-galactose. We found that free soybean isoflavones and peptides increased after soy milk was fermented by Lactobacillus fermentum CQPC04. The in vivo results indicated that L. fermentum CQPC04-fermented soy milk enhanced the organ index of the liver and spleen, and improved the pathological morphology of the liver, spleen, and skin. L. fermentum CQPC04-fermented soy milk increased the enzymatic activity of glutathione peroxidase (GSH-Px), total superoxide dismutase (T-SOD), and catalase (CAT), increased glutathione (GSH), but decreased the levels of nitric oxide (NO) and malondialdehyde (MDA) in serum, liver, and brain tissues of oxidative aging mice. The above mentioned fermented soy milk also increased the levels of collagen I (Col I), hyaluronic acid (HA), and collagen III (Col III), and decreased the levels of advanced glycation End products (AGEs) and hydrogen peroxide (H2O2). The RT-qPCR results showed that L. fermentum CQPC04-fermented soy milk upregulated the mRNA expression of nuclear factor erythroid 2?related factor (Nrf2), heme oxygenase-1 (HMOX1), quinone oxido-reductase 1 (Nqo1), neuronal nitric oxide synthase (NOS1), endothelial nitric oxide synthase (NOS3), Cu/Zn–superoxide dismutase (Cu/Zn-SOD), Mn–superoxide dismutase (Mn-SOD), and CAT, but downregulated the expression of inducible nitric oxide synthase (NOS2) and glutamate cysteine ligase modifier subunit (Gclm) in liver and spleen tissues. Lastly, the fermented soy milk also increased the gene expression of Cu/Zn-SOD, Mn-SOD, CAT, GSH-Px, matrix metalloproteinases 1 (TIMP1), and matrix metalloproteinases 2 (TIMP2), and decreased the expression of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) in skin tissue. In conclusion, L. fermentum CQPC04-fermented soy milk was able to satisfactorily delay oxidative aging effects, and its mechanism may be related to the increase in free soy isoflavones and peptides.
Modified Atmosphere Packaging Maintains the Sensory and Nutritional Qualities of Post-harvest Baby Mustard During Low-Temperature Storage
Authors: Lin Peixing , Di Hongmei , Wang Guiyuan , Li Zhiqing , Li Huanxiu , Zhang Fen , Sun Bo
Published: September 2021

Baby mustard is a popular, yet highly perishable, Brassica vegetable. There is a need to develop effective methods for maintaining post-harvest qualities of baby mustard. Here, the lateral buds of baby mustard were packed in transparent polyethylene bags with no holes (M0), 6 mm in diameter holes (M1), or 12 mm in diameter holes (M2) and stored at 4°C. The effect of different modified atmosphere packaging (MAP) treatments on the sensory quality, health-promoting compounds, and antioxidant capacity was investigated by comparison with non-wrapped baby mustard. M1 and M2 delayed sensory quality deterioration and slowed declines in the content of ascorbic acid, total phenolics, and glucosinolates and antioxidant capacity during storage. M1 was most effective in prolonging the shelf life (three additional days compared with control lateral buds) and maintaining the content of glucosinolates. However, M0 accelerated the decline in the odor score, acceptability score, and ascorbic acid content and shortened the shelf life of baby mustard by more than 5 d compared with the control. These findings indicate that the effect of MAP treatment depends on the size of the holes in the bag. Based on these results, M1 was an alternative method for prolonging the shelf life and maintaining post-harvest qualities of baby mustard stored at 4°C.
High Variability in Cellular Proliferation, Gene Expression, and Cytokine Production in the Nonneoplastic Colonic Epithelium of Young Apc+/Min-FCCC Mice
Authors: Leystra Alyssa A. , Harvey Kristen N. , Kaunga Esther , Hensley Harvey , Vanderveer Lisa A. , Devarajan Karthik , Clapper Margie L.
Published: September 2021

An urgent need exists to identify efficacious therapeutic preventive interventions for individuals who are at high risk of developing colorectal cancer. To maximize the benefits of preventive intervention, it is vital to identify the time interval during which the initiation of a preventive intervention will lead to an optimal outcome. The goal of the present study was to determine if oncogenic events can be detected in the nonneoplastic colonic mucosa of Apc+/Min-FCCC mice prior to formation of the first adenoma, thus defining an earlier point of intervention along the cancer continuum. Tissues taken at three potential points of intervention were characterized: prior to Apc mutation (wild type Apc+/+-FCCC mice); after initiation but prior to colon adenoma formation (tumor-free Apc+/Min-FCCC mice); and after formation of the first colon adenoma (tumor-bearing Apc+/Min-FCCC mice). Experimentation focused on molecular processes that are dysregulated in early colon lesions: 1) cellular proliferation (proliferative index and size of the proliferative zone); 2) cellular stemness (expression of Ascl2, Grem1, Lgr5 and Muc2); 3) EGFR signaling (expression of Ereg); and 4) inflammation (expression of Mmp9, Ptsg2, and Reg4, as well as secretion of 18 cytokines involved in immune activation and response). Interestingly, the nonneoplastic colonic mucosa of wild type, tumor-free Apc+/Min-FCCC, and tumor-bearing Apc+/Min-FCCC mice did not display significant differences in average epithelial cell proliferation (fold change 0.8–1.3, p≥0.11), mucosal gene expression (fold change 0.8–1.4, p≥0.22), or secretion of specific cytokines from colonic mucosa (fold change 0.2–1.5, p≥0.06). However, the level of cytokine secretion was highly variable, with many (22% of wild type, 31% of tumor-free Apc+/Min-FCCC, and 31% of tumor-bearing Apc+/Min-FCCC) mice categorized as outliers (> 1.5 x interquartile ranges below the first quartile or above the third quartile) due to elevated expression of at least one cytokine. In summary, no differences were observed in proliferation, stemness, and EGFR signaling in the colonic mucosa of wild type vs Apc+/Min-FCCC mice, with low baseline cytokine expression, prior to the formation of the first colon adenoma. The results of this study provide valuable baseline data to inform the design of future cancer prevention studies.