bluuebunny/crossref_metadata_2025 huggingface dataset:
Rejecting Novel Motions in High-Density Myoelectric Pattern Recognition Using Hybrid Neural Networks
Authors: Wu Le , Chen Xun , Chen Xiang , Zhang Xu
Published: March 2022

The objective of this study is to develop a method for alleviating a novel pattern interference toward achieving a robust myoelectric pattern-recognition control system. To this end, a framework was presented for surface electromyogram (sEMG) pattern classification and novelty detection using hybrid neural networks, i.e., a convolutional neural network (CNN) and autoencoder networks. In the framework, the CNN was first used to extract spatio-temporal information conveyed in the sEMG data recorded via high-density (HD) 2-dimensional electrode arrays. Given the target motion patterns well-characterized by the CNN, autoencoder networks were applied to learn variable correlation in the spatio-temporal information, where samples from any novel pattern appeared to be significantly different from those from target patterns. Therefore, it was straightforward to discriminate and then reject the novel motion interferences identified as untargeted and unlearned patterns. The performance of the proposed method was evaluated with HD-sEMG data recorded by two 8 × 6 electrode arrays placed over the forearm extensors and flexors of 9 subjects performing seven target motion tasks and six novel motion tasks. The proposed method achieved high accuracies over 95% for identifying and rejecting novel motion tasks, and it outperformed conventional methods with statistical significance (p < 0.05). The proposed method is demonstrated to be a promising solution for rejecting novel motion interferences, which are ubiquitous in myoelectric control. This study will enhance the robustness of the myoelectric control system against novelty interference.
Musculoskeletal Pain in Parkinson's Disease
Authors: Li Jun , Zhu Ben-Fan , Gu Zhu-Qin , Zhang Hui , Mei Shan-Shan , Ji Shao-Zhen , Liu Shu-Ying , Han Chao , Chen Huai-Zhen , Chan Piu
Published: March 2022

Background

Musculoskeletal pain is commonly experienced in patients with Parkinson's disease (PD). Few studies have investigated the clinical characteristics and risk factors associated with musculoskeletal pain.

Objectives

To investigate the distribution, clinical characteristics, and factors associated with musculoskeletal pain in a large sample of patients with PD.

Methods

We enrolled 452 patients from two clinics and used a standardized questionnaire to collect demographic and clinical information. Musculoskeletal pain was diagnosed based on the Ford Classification System, and pain severity was assessed with the numeric rating scale (NRS). Multivariate regression models explored the association between clinical features of PD and quality of life and pain.

Results

Two hundred and six patients (45.58%) reported musculoskeletal pain, typically in their lower limbs and backs. Levodopa resulted in a ≥30% reduction in pain intensity scores in 170 subjects. Female sex (odds ratio [OR], 1.57; 95% CI, 1.07–2.29) and Levodopa-equivalent daily doses (LEDDs; OR, 3.35; 95% CI, 1.63–6.59) were associated with an increased risk for musculoskeletal pain. Pain duration (p = 0.017), motor symptoms (p < 0.001), and depression (p < 0.001) were significantly associated with quality of life.

Conclusions

The lower limbs and back are common sites of musculoskeletal pain in patients with PD, and up to 82.52% of patients were responsive to Levodopa. Female sex and LEDDs are associated with musculoskeletal pain, suggesting that dopamine deficiencies, and not the motor and non-motor impairment, might be the most critical baseline risk factor of musculoskeletal pain.
Diagnostic Yield and Complication Rate of Stereotactic Biopsies in Precision Medicine of Gliomas
Authors: Katzendobler Sophie , Do Anna , Weller Jonathan , Dorostkar Mario M. , Albert Nathalie L. , Forbrig Robert , Niyazi Maximilian , Egensperger Rupert , Thon Niklas , Tonn Joerg Christian , Quach Stefanie
Published: March 2022

Background

An integrated diagnosis consisting of histology and molecular markers is the basis of the current WHO classification system of gliomas. In patients with suspected newly diagnosed or recurrent glioma, stereotactic biopsy is an alternative in cases in which microsurgical resection is deemed to not be safely feasible or indicated. In this retrospective study, we aimed to analyze both the diagnostic yield and the safety of a standardized biopsy technique.

Material and Methods

The institutional database was screened for frame-based biopsy procedures (January 2016 until March 2021). Only patients with a suspected diagnosis of glioma based on imaging were included. All tumors were classified according to the current WHO grading system. The clinical parameters, procedural complications, histology, and molecular signature of the tissues obtained were assessed.

Results

Between January 2016 and March 2021, 1,214 patients underwent a stereotactic biopsy: 617 (50.8%) for a newly diagnosed lesion and 597 (49.2%) for a suspected recurrence. The median age was 56.9 years (range 5 months−94.4 years). Magnetic resonance imaging (MRI)-guidance was used in 99.3% of cases and additional positron emission tomography (PET)-guidance in 34.3% of cases. In total, stereotactic serial biopsy provided an integrated diagnosis in 96.3% of all procedures. The most frequent diagnoses were isocitrate dehydrogenase (IDH) wildtype glioblastoma (n = 596; 49.2%), oligodendroglioma grade 2 (n = 109; 9%), astrocytoma grade 3 (n = 108; 8.9%), oligodendroglioma grade 3 (n = 76; 6.3%), and astrocytoma grade 2 (n = 66; 5.4%). A detailed determination was successful for IDH 1/2 mutation in 99.4% of cases, for 1p/19q codeletion in 97.4% of cases, for TERT mutation in 98.9% of cases, and for MGMT promoter methylation in 99.1% of cases. Next-generation sequencing was evaluable in 64/67 (95.5%) of cases and DNA methylome analysis in 41/44 (93.2%) of cases. Thirteen (1.1%) cases showed glial tumors that could not be further specified. Seventy-three tumors were different non-glioma entities, e.g., of infectious or inflammatory nature. Seventy-five out of 597 suspected recurrences turned out to be post-therapeutic changes only. The rate of post-procedural complications with clinical symptoms of the Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher was 1.2% in overall patients and 2.6% in the subgroup of brainstem biopsies. There was no fatal outcome in the entire series.

Conclusion

Image-guided stereotactic serial biopsy enables obtaining reliable histopathological and molecular diagnoses with a very low complication rate even in tumors with critical localization. Thus, in patients not undergoing microsurgical resection, this is a valuable tool for precision medicine of patients with glioma.
The LINC00452/miR-204/CHST4 Axis Regulating Thymic Tregs Might Be Involved in the Progression of Thymoma-Associated Myasthenia Gravis
Authors: Wang Fuqiang , Zhang Hanlu , Qiu Guanghao , Li Zhiyang , Wang Yun
Published: March 2022

Background

Myasthenia gravis (MG) is an autoimmune disease that mainly affects neuromuscular junctions and is usually associated with immune disorders in the thymoma. The competitive endogenous RNA (ceRNA) hypothesis has been demonstrated to be an intrinsic mechanism regulating the development of several autoimmune diseases; however, the mechanism where the ceRNA network regulates immune cells in patients with thymoma-associated MG (TAMG) has rarely been explored.

Methods

RNA-seq data and clinical information of 124 patients with thymoma were obtained from The Cancer Genome Atlas (TCGA) database. The patients were divided into two groups according to whether they were diagnosed with MG. We applied the propensity score matching method to reduce the incidence of baseline confounders. We then constructed a ceRNA network with differentially expressed RNAs between the groups based on four public databases. The expression of genes of interest was validated by qPCR. Moreover, we predicted the immune cells that infiltrated the thymoma and then analyzed the association between immune cells and RNA in the ceRNA network. To further determine the function of the mRNAs associated with immune cells in patients with TAMG, we performed gene set enrichment analysis in thymoma patients with MG.

Results

After matching, 94 patients were included in the following analysis. A total of 847 mRNAs, 409 lncRNAs, and 45 miRNAs were differentially expressed between the groups. The ceRNA network, including 18 lncRNAs, four miRNAs, and 13 mRNAs, was then constructed. We then confirmed that CHST4 and LINC00452, miR-204-3p and miR-204-5p were differentially expressed between patients with TAMG and thymoma patients without MG (NMG) by qPCR. Moreover, we found that the percentage of predicted regulatory T (Treg) cells was significantly decreased in patients with TAMG. Further analysis indicated that the LINC00452/miR-204/CHST4 axis might regulate thymic regulatory T cells (Tregs) in the progression of MG.

Conclusions

In this research, we constructed a ceRNA network involved in the progression of TAMG, discovered that thymic Tregs were significantly decreased in patients with TAMG, and assumed that the LINC00452/miR-204/CHST4 axis may regulate thymic Tregs in the development of TAMG. These findings may deepen our understanding of the roles of the ceRNA network in regulating TAMG and highlight the function of CHST4 in recruiting peripheral T cells in the progression of TAMG.
Toward a Digital Health Intervention for Vestibular Rehabilitation: Usability and Subjective Outcomes of a Novel Platform
Authors: Meldrum Dara , Murray Deirdre , Vance Roisin , Coleman Sarah , McConnell Sonya , Hardiman Orla , McConn Walsh Rory
Published: March 2022

Digital technologies are increasingly available and are reducing in cost. There is an opportunity to move to a digital health approach in vestibular rehabilitation (VR), but there is a paucity of suitable systems available and a consequent lack of evidence to support their use. This study aimed to investigate a novel digital platform developed specifically for VR (comprising clinician software, a wearable sensor, and a patient-facing app). Participants (n = 14, 9F:5M, mean age 59) with vestibular dysfunction and imbalance used the app for treatment, and therapists (n = 4) used the platform to deliver VR in the form of individualized exercise programmes over a mean of 17.4 ± 8.8 weeks. Outcomes included the system usability scale, the patient enablement instrument (PEI), change in subjective symptoms (numerical rating scales), percentage adherence to prescribed exercise, and a semi-structured interview on utility. A significant reduction was found in symptoms of vertigo/dizziness (p < 0.004), imbalance (p < 0.002), oscillopsia (p < 0.04), and anxiety (p < 0.02) after use. System usability scores were high for both clinicians (mean 85/100) and participants (mean 82.7/100) and high enablement was reported (mean PEI 6.5/12). Overall percentage adherence to the exercise prescription was highly variable and ranged from 4 to 78% when measured digitally. At semi-structured interviews, participants reported a high level of acceptance and satisfaction with digital delivery, and no adverse events were recorded. When COVID-19 restrictions eased, 2 participants trialed the head sensor with the application and found it highly usable. Further research is required to investigate the efficacy and how the wearable sensor impacts the delivery of care.
Efficacy and Safety of Tacrolimus Therapy for a Single Chinese Cohort With Very-Late-Onset Myasthenia Gravis
Authors: Zheng Yiming , Yuan Xiaoqiu , Zhang Caifeng , Liu Ran , Jin Haiqiang , Hao Hongjun , Li Fan , Zhao Yawen , Yuan Yun , Wang Zhaoxia , Gao Feng
Published: March 2022

Background and Purpose

Previous studies have found tacrolimus to be a favorable drug for treating different types of myasthenia gravis (MG), but few have focused on very-late-onset MG (VLOMG). This study evaluated the efficacy and safety of tacrolimus for VLOMG therapy.

Methods

This was a retrospective single-center cohort study of 70 patients with VLOMG (onset ≥65 years) who visited Peking University First Hospital in 2019. Participants were divided into the tacrolimus (Tac) group and the control group based on tacrolimus usage. We further divided the Tac group into patients treated without corticosteroids and with corticosteroids. Sociodemographic features, clinical profiles, and outcomes were compared between different therapies and further analyzed by multivariate regression. Details of tacrolimus treatment, comorbidities, and adverse drug reactions (ADRs) were described.

Results

Among 70 patients, the median (interquartile range) age at onset was 71 (68–77) years, and the follow-up duration was 27 (27-29) months. Most patients were types I (28%) and III (40%) according to the MG Foundation of America (MGFA) classification. In the Tac group, tacrolimus treatment was maintained for 36 (27-38) months. The dosage at the final evaluation was 1.0 (1.0–1.75) mg/day, and the last blood concentration test was 4.25 (2.85–5.7) ng/ml. A total of 43% reached remission, and 37% improved based on MGFA postintervention status (MGFA-PIS). For the 9 patients, newly diagnosed at enrollment within this group, MG activities of daily living (MG-ADL) decreased significantly from 3 (2-5) to 2 (1-2) (p= 0.041). Regarding the 13 patients, coadministering Wuzhi capsules the tacrolimus concentration increased from 2.75 (1.4–3.8) ng/ml to 5.95 (5.1–7.0) ng/ml (p= 0.012). No significant differences in outcomes were observed between tacrolimus treatment without and with corticosteroids or between the Tac group and the control group. A total of 93% had at least one comorbidity. ADRs related to tacrolimus emerged in 25% (9/36) of patients, most of which were not serious and reversible.

Conclusions

Tacrolimus is effective and safe in treating VLOMG. Tacrolimus monotherapy without corticosteroids can be used as an initial and maintenance treatment for VLOMG. Wuzhi capsules work well in elevating tacrolimus concentrations in this population.
Physical Capacity and Activity in Patients With Idiopathic Normal Pressure Hydrocephalus
Authors: Rydja Johanna , Kollén Lena , Ulander Martin , Tullberg Mats , Lundin Fredrik
Published: March 2022

Introduction

Most patients with idiopathic normal pressure hydrocephalus (iNPH) improve gait after surgery. However, knowledge on physical capacity and activity after shunt surgery is limited. One of the aims of this study was to evaluate the effect of shunt surgery in patients with iNPH on short-distance walking, functional exercise capacity, functional strength, and variables of activity and sleep, 3 and 6 months postoperatively. Another aim was to evaluate the effect of a physical exercise program. Additionally, we studied how changes in short-distance walking were correlated with functional exercise capacity and voluntary walking.

Methods

In total, 127 patients were consecutively included and randomized to the exercise group (n = 62) or the control group (n = 65). Participants in the exercise group underwent the supervision of a 12-week exercise program. All patients were assessed before surgery, at 3 and 6 months postoperatively with the 10-m walk test (10MWT), the 6-min walk test (6MWT), 30-s chair stand test (30sCST), and with the actigraphic recordings of activity variables measured for a total of 24 h/day for at least 3 days.

Results

All patients improved at 3 months postoperatively in the 10MWT (p < 0.001), 6MWT (p < 0.001), and 30sCST (p < 0.001). These results were maintained after 6 months. Actigraphic recordings for voluntary walking (steps per minute) were improved and nighttime sleep (%) increased after 6 months (p = 0.01, p = 0.04). There were no significant differences between the exercise group and the control group, except for the postoperative change in the proportion of daytime sleep after 3 months, which was slightly more reduced compared to baseline in the exercise group (p = 0.04). Changes after 3 months in the 10MWT and 6MWT were moderately correlated (ρ= −0.49, p = 0.01) whereas the correlation between the 10MWT and voluntary walking was weak (ρ = −0.34, p = 0.01).

Conclusion

Shunt surgery improved short-distance walking, functional exercise capacity, functional strength, and voluntary walking. An exercise program did not affect these outcomes. Short-distance walking was weakly correlated with voluntary walking, indicating improved physical capacity does not directly translate to increased physical activity. Further research should address how interventions should be tailored to promote physical activity after shunt surgery.

Trial Registration

clinicaltrials.gov, Id: NCT02659111.
Understanding Magnetic Resonance Imaging in Multiple Sclerosis (UMIMS): Development and Piloting of an Online Education Program About Magnetic Resonance Imaging for People With Multiple Sclerosis
Authors: Freund Magalie , Schiffmann Insa , Rahn Anne Christin , Chard Declan , Lukas Carsten , Scheiderbauer Jutta , Sippel Anna , Heesen Christoph
Published: March 2022

Background

People with multiple sclerosis (pwMS) lack sufficient magnetic resonance imaging (MRI) knowledge to truly participate in frequently occurring MRI-related therapy decisions. An evidence-based patient information (EBPI) about MRI is currently lacking.

Objective

The aim of this study was to develop an evidence-based online education program about limitations and benefits of MRI for pwMS. Ultimately, our goal was to improve MRI risk-knowledge, empower pwMS, and promote shared decision-making.

Methods

The program's contents were based on literature research and a previous pilot study. It was revised following 2 evaluation rounds with pwMS, MRI experts and expert patients. In a pilot study, n = 92 pwMS received access to the program for 4 weeks. User experiences and acceptance, MRI knowledge (MRI-RIKNO 2.0 questionnaire) and emotions and attitudes toward MRI (MRI-EMA questionnaire) were assessed. Results were compared to a previous survey population of n = 508 pwMS without access to the program.

Results

Participants rated the program as easy to understand, interesting, relevant, recommendable, and encouraging. In comparison to pwMS without access to the program, MRI risk-knowledge and perceived MRI competence were higher.

Conclusion

Satisfaction with the program and good MRI-risk knowledge after usage demonstrates the need and applicability of EBPI about MRI in MS.
Novel Predictors of Stroke-Associated Pneumonia: A Single Center Analysis
Authors: Li Ya-ming , Zhao Li , Liu Yue-guang , Lu Yang , Yao Jing-zhu , Li Chun-ju , Lu Wei , Xu Jian-hua
Published: March 2022

Stroke-associated pneumonia (SAP) is a common cause of disability or death. Although the researches on SAP have been relatively mature, the method that can predict SAP with great accuracy has not yet been determined. It is necessary to discover new predictors to construct a more accurate predictive model for SAP. We continuously collected 2,366 patients with acute ischemic stroke, and then divided them into the SAP group and non-SAP group. Data were recorded at admission. Through univariate analyses and multivariate regression analyses of the data, the new predictive factors and the predictive model of SAP were determined. The receiver operating characteristic (ROC) curve and the corresponding area under the curve (AUC) were used to measure their predictive accuracy. Of the 2,366 patients, 459 were diagnosed with SAP. International normalized ratio (INR) (odds ratio = 37.981; 95% confidence interval, 7.487–192.665; P < 0.001), age and dysphagia were independent risk factors of SAP. However, walking ability within 48 h of admission (WA) (odds ratio = 0.395; 95% confidence interval, 0.287–0.543; P < 0.001) was a protective factor of SAP. Different predictors and the predictive model all could predict SAP (P < 0.001). The predictive power of the model (AUC: 0.851) which included age, homocysteine, INR, history of chronic obstructive pulmonary disease (COPD), dysphagia, and WA was greater than that of age (AUC: 0.738) and INR (AUC: 0.685). Finally, we found that a higher INR and no WA could predict SAP in patients with acute ischemic stroke. In addition, we designed a simple and practical predictive model for SAP, which showed relatively good accuracy. These findings might help identify high-risk patients with SAP and provide a reference for the timely use of preventive antibiotics.
Segmentation of Spontaneous Intracerebral Hemorrhage on CT With a Region Growing Method Based on Watershed Preprocessing
Authors: Zhou Zhengsong , Wan Hongli , Zhang Haoyu , Chen Xumiao , Wang Xiaoyu , Lili Shiluo , Zhang Tao
Published: March 2022

Intracerebral hemorrhage (ICH) poses a great threat to human life due to its high incidence and poor prognosis. Identification of the bleeding location and quantification of the volume based on CT images are of great significance for assisting the diagnosis and treatment of ICH. In this study, a region-growing algorithm based on watershed preprocessing (RG-WP) was proposed to segment and quantify the hemorrhage. The lowest points yielded by the watershed algorithm were used as seed points for region growing and then hemorrhage was segmented based on the region growing method. At the same time, to integrate the rich experience of clinicians with the algorithm, manual selection of seed points on the basis of watershed segmentation was performed. With the application of segmentation on CT images of 55 patients with ICH, the performance of the RG-WP algorithm was evaluated by comparing it with manual segmentations delineated by professional clinicians as well as the traditional ABC/2 method and the deep learning algorithm U-net. The mean deviation of hemorrhage volume of the RG-WP algorithm from manual segmentation was −0.12 ml (range: −1.05–1.16), while that of the ABC/2 from the manual was 1.05 ml (range: −0.77–9.57). Strong agreement of the algorithm and the manual was confirmed with a high intraclass correlation coefficient (ICC) (0.998, 95% CI: 0.997–0.999), which was superior to that of the ABC/2 and the manual (0.972, 95% CI: 0.953–0.984). The sensitivity (Sen), positive predictive value (PPV), dice similarity index (DSI), and Jaccard index (JI) of the RG-WP algorithm compared to the manual were 0.92 ± 0.04, 0.95 ± 0.04, 0.93 ± 0.02, and 0.88 ± 0.04, respectively, showing high consistency. Besides, the accuracy of the algorithm was also comparable to that of the deep learning method U-net, with Sen, PPV, DSI, and JI being 0.91 ± 0.09, 0.91 ± 0.06, 0.91 ± 0.05, and 0.91 ± 0.06, respectively.
Neuroanatomical Correlates of Mild-to-Moderate Depression: Memory Ability Mediates the Association Between Gray Matter Volume and Antidepressant Treatment Outcome
Authors: Li Hong , Wang Junjie , Liu Sha , Liu Zhifen , Xu Yong
Published: March 2022

Mild-to-moderate depression (MMD) is frequently encountered in clinical practice. Investigating the brain mechanism and its relationship with symptoms in patients with MMD can help us understand the occurrence and development of depression, thus optimizing the prevention and treatment of depression. Shugan Jieyu capsule (SG), a traditional Chinese medicine, is commonly used to ameliorate emotional and cognitive symptoms induced by patients with MMD. Combining clinical assessments and magnetic resonance imaging (MRI), we obtained the emotional and cognitive status of MMD patients and also explored the structural and functional alterations in MMD patients after SG treatments. Structural MRI demonstrated that the gray matter volumes of the left thalamus, right thalamus, and right amygdala in MMD patients were significantly smaller than in healthy controls, and the right amygdala volume was negatively related to depression symptoms in MMD patients. Resting-state functional MRI data demonstrated that MMD patients exhibited decreased temporal coupling between the right amygdala and nucleus accumbens, which was further associated with the severity of depression. Furthermore, right amygdala volume at baseline served as a significant predictor to identify the treatment outcome after 8 weeks of SG treatment in the patients’ group, and importantly, the memory ability mediated the relationship from right amygdala volume to the treatment outcome. These data revealed the structural and functional deficits in the right amygdala, which were highly correlated with the symptoms of depression and its cognitive ability, likely predicting treatment outcome. Therefore, this study strengthened our understanding of the pathogenesis of MMD, which is hoped that it will contribute to tailoring a personalized method for treating the patients.
Of Humans and Gerbils— Independent Diversification of Neuroligin-4 Into X- and Y-Specific Genes in Primates and Rodents
Authors: Maxeiner Stephan , Benseler Fritz , Brose Nils , Krasteva-Christ Gabriela
Published: March 2022

The neural cell adhesion protein neuroligin-4 has puzzled neuroscientists and geneticist alike for almost two decades. Its clinical association with autism spectrum disorders (ASD) is well established, however, its diversification into sex chromosome-specific copies,NLGN4XandNLGN4Y, remains uncharted territory. Just recently, the presence of substantial neuroligin-4 sequence differences between humans and laboratory mice, in whichNlgn4is a pseudoautosomal gene, could be explained as a consequence of dramatic changes affecting the pseudoautosomal region on both sex chromosomes in a subset of rodents, the clade eumuroida. In this study, we describe the presence of sex chromosome-specific copies of neuroligin-4 genes in the Mongolian gerbil (Meriones unguiculatus) marking the first encounter of its kind in rodents. Gerbils are members of the family Muridae and are closely related to mice and rats. Our results have been incorporated into an extended evolutionary analysis covering primates, rodents, lagomorphs, treeshrews and culogos comprising together the mammalian superorder euarchontoglires. We gathered evidence that substantial changes in neuroligin-4 genes have also occurred outside eumuroida in other rodent species as well as in lagomorphs. These changes feature, e.g., a general reduction of its gene size, an increase in its average GC-content as well as in the third position (GC3) of synonymous codons, and the accumulation of repetitive sequences in line with previous observations. We further show conclusively that the diversification of neuroligin-4 in sex chromosome-specific copies has happened multiple times independently during mammal evolution proving that Y-chromosomalNLGN4Ygenes do not originate from a single commonNLGN4Yancestor.
Determination of Antiviral Mechanism of Centenarian Gut-Derived Limosilactobacillus fermentum Against Norovirus
Authors: Li Ying , Gao Junshan , Xue Liang , Shang Yanyan , Cai Weicheng , Xie Xinqiang , Jiang Tong , Chen Huizhen , Zhang Jumei , Wang Juan , Chen Moutong , Ding Yu , Wu Qingping
Published: March 2022

Although noroviruses are the causative agents of most non-bacterial foodborne disease outbreaks, effective antivirals are currently unavailable. Certain probiotic strains have been reported as active antivirals for norovirus infections, but their mechanisms have not been fully elucidated. Herein, we examined the antiviral potential of 122 lactic acid bacteria isolates against murine norovirus (MNV), a human norovirus surrogate. A centenarian gut-derived strain, Limosilactobacillus fermentum PV22, exhibited the strongest MNV antagonism and reduced the viral titer by 2.23 ± 0.38 (log-value) in 5 min with stable activity at 25°C (P < 0.01). Genome mining revealed that its antiviral activity can be attributed to the synthesis of γ-aminobutyric acid, and this finding was experimentally verified. Furthermore, we demonstrated the safety of the isolate and its high intestinal colonization ability. In conclusion, we discovered a centenarian gut-derived L. fermentum strain with strong anti-norovirus activity and identified its antiviral metabolite. Our results will offer new solutions for the prevention and treatment of food-related norovirus infections.
Comparative Analysis of the Bioactive Compounds in Chicken Cartilage: Protective Effects of Chondroitin Sulfate and Type II Collagen Peptides Against Osteoarthritis Involve Gut Microbiota
Authors: Zhang Hongru , Qi Liwei , Shen Qingshan , Wang Ruiqi , Guo Yujie , Zhang Chunhui , Richel Aurore
Published: March 2022

This study was designed to explore osteoarthritis (OA) treatment from bioactive compounds of chicken cartilage food supplements. The OA rat model induced by sodium iodoacetate was used to evaluate the treatment effect in vivo. In this study, we used animal experiments to show that oral chondroitin sulfate (CS), cartilage powder, and type II collagen peptides could increase the athletic ability of rats and reduce inflammatory cytokine levels in serum or synovial fluid, including prostaglandin E2, tumor necrosis factor-α, interleukin (IL) 1β, IL-6, and IL-17. CS displayed the best treatment effect against OA. The morphological structure of articular cartilage indicated that CS could significantly improve cartilage tissue morphology and reduce OA score. Oral CS slowed down the development of OA by modulating gut microbiota. These results provided a useful scientific basis for the high-value utilization of chicken cartilage.
Transarterial Chemoembolization Combined With Tyrosine Kinase Inhibitors for Intermediate‐Stage Hepatocellular Carcinoma, What Else Can We Do?
Authors: Deng Jun , Wen Feng
Published: March 2022

Transarterial chemoembolization (TACE) has been considered the standard treatment for intermediate-stage hepatocellular carcinoma (HCC). However, intermediate‐stage HCC is highly heterogeneous with a broad population with varying tumour burdens, liver function. This suggests that TACE monotherapy treatment might not be suitable for all patients with intermediate‐stage HCC. The administration of tyrosine kinase inhibitors (TKIs) has become an important treatment option for improving the prognosis of patients with advanced HCC. Over the years, several trials have been conducted to explore the effects of TACE combined with TKIs for intermediate-stage HCC. However, the clinical efficacy is still controversial, and its potential clinical utility needs to be confirmed. This review will focus on the recent progress of TACE combined TKIs for intermediate-stage HCC.
Bibliometric Analysis of Global Research on Perinatal Palliative Care
Authors: Wang Yiting , Shan Chunjian , Tian Yingying , Pu Congshan , Zhu Zhu
Published: March 2022

Objectives

The aim of this study was to perform a bibliometric analysis of publications related to perinatal palliative care to identify scientific output and research trends at a global level.

Methods

The Web of Science Core Collection database was searched to retrieve publications focusing on perinatal palliative care published between 2001 and 2020. All retrieved publications were identified by title and abstract for their relevance to perinatal palliative care. These eligible publications were extracted from the following data: title, abstract, year, keywords, author, organization, journal and cited literature. VOSviewer software was used to conduct bibliographic coupling, coauthorship, and cooccurrence analyses and to detect publication trends in perinatal palliative care research.

Results

A total of 114 publications concerning perinatal palliative care were included. The annual number of publications has increased dramatically in recent years. The United States has made the largest contribution to this field with the majority of publications (68, 59.6%) and citations (1,091, 70.5%) and with close collaborations with researchers in Canada, Portugal and Australia. Wool C and her institution, York College of Pennsylvania, are the respectively, most prolific author and institution in this field, publishing 18 papers (15.8%). Journal of Palliative Medicine is the leading and main journal in this field. According to the cooccurrence network analysis, five main research topics were identified: the candidates for PPC, service models and forms, framework components, parental perspectives and satisfaction, and challenges and needs of health care providers.

Conclusion

The findings of this bibliometric study illustrate the current state and global trends of perinatal palliative care for the past two decades, which will help researchers determine areas of research focus and explore new directions for future research in this field.
A Human Conditionally Immortalized Proximal Tubule Epithelial Cell Line as a Novel Model for Studying Senescence and Response to Senolytics
Authors: Yang Yi , Mihajlovic Milos , Valentijn Floris , Nguyen Tri Q. , Goldschmeding Roel , Masereeuw Rosalinde
Published: March 2022

Accumulating evidence suggests that senescence of kidney tubule epithelial cells leads to fibrosis. These cells secrete senescence-associated secretory phenotype (SASP) factors that are involved in diverse signaling pathways, influencing kidney fibrosis. Here, we investigated whether our previously established conditionally immortalized proximal tubule epithelial cell line overexpressing the organic anion transporter 1 (ciPTEC-OAT1) can be used as a valid in vitro model to study kidney senescence and senolytics response. CiPTEC-OAT1 proliferates rapidly at 33°C and exhibits a “senescence-like” arrest at 37°C, most likely due to suppression of SV40T expression and subsequent reactivation of the p53 and Rb pathways. To understand how permissive (33°C) and non-permissive (37°C) temperatures of the cell culture affect the senescence phenotype, we cultured ciPTEC-OAT1 for up to 12 days and evaluated the apoptosis and SASP markers. Day 0 in both groups is considered as the non-senescence group (control). Further, the potential of navitoclax, dasatinib, quercetin, and the combination of the latter two to clear senescent cells was evaluated. Maturation of ciPTEC-OAT1 at non-permissive temperature affected mRNA and protein levels of senescence markers. A remarkable upregulation in p21 gene expression was found in the non-permissive temperature group, whereas expression of Lamin B1 decreased significantly. SASP factors, including PAI-1A, IL-1β, CTGF, and IL-6 were upregulated, but no significant difference in Bcl-2 and Bcl-xl were found in the non-permissive temperature group. After culturing ciPTEC-OAT1 up to 12 days, cells in the non-permissive temperature group showed an upregulation in the apoptosis-associated proteins Bcl-2, BID, and Bax, and a downregulation in Mcl-1, Bad, Bak, and Bim at various time points. Further, Bcl-xl, Puma, Caspase 3, Caspase 7, and Caspase 9 showed initial upregulations followed by downregulations at later time points. The loss of Lamin B1, upregulation of SA-β-gal expression and increase in its activity, upregulation of p21 levels and downregulation of p53, along with the upregulation of SASP factors, confirmed that maturation at 37°C promotes senescence features. Finally, the senolytics response was evaluated by testing cell viability following exposure to senolytics, to which cells appeared dose-dependently sensitive. Navitoclax was most effective in eliminating senescent cells. In conclusion, culturing ciPTEC-OAT1 at 37°C induces a senescence phenotype characterized by increased expression of cell cycle arrest and anti-apoptosis markers, SASP factors, and responsiveness to senolytics treatment. Therefore, ciPTEC-OAT1 represents a valid model for studying kidney senescence by simply adjusting culture conditions.
Efficacy and Safety of Chinese Patent Medicine for the Prevention and Treatment of Radiotherapy and Chemotherapy-Induced Oral Mucositis: A Systematic Review and Meta-Analysis
Authors: Xie Yufei , Fang Xin , Hua Hong , Zhou Peiru
Published: March 2022

Background: Radiotherapy and chemotherapy-induced oral mucositis can affect cancer patients’ quality of life, even necessitate cancer therapy and influence prognosis. Chinese patent medicines (CPMs) have been widely used as complementary alternative medicines for the prevention and treatment of oral mucositis, and their efficacy and safety require further evaluation. Therefore, this study was conducted to provide references for clinical practice.

Methods: Ten databases were searched electronically and manually to identify randomized controlled trials (RCTs) from their inception to August 2021, concerning the prevention and treatment of radiotherapy and chemotherapy-induced oral mucositis with CPMs. The prevalence, pain level, and the severity of radiotherapy and chemotherapy-induced oral mucositis, as well as the effectiveness rate and adverse effects of CPMs, were set as the outcome criteria. The assessment criteria of the Cochrane Handbook were used to determine study quality and bias, and meta-analysis was conducted using Review Manager 5.4.1 software.

Results: A total of 2,312 cases from 27 RCTs were included. Most studies were considered to have a low or unclear risk of bias. More research is available on the use of CPMs in the prevention of radiotherapy and chemotherapy-induced oral mucositis than in its treatment. As for the prevention, it was proved that CPMs could significantly reduce the prevalence of radiotherapy and chemotherapy-induced oral mucositis, especially for the severe types, and decrease pain levels (p < 0.05). For treatment, CPMs could alleviate the symptoms, promote the healing of ulceration in radiotherapy and chemotherapy-induced oral mucositis, and thus improve the efficiency of clinical treatment (p < 0.05). The results of subgroup analyses were mainly consistent with the above results. The adverse effects of CPMs mainly included gastrointestinal reactions and bitter taste, and no serious adverse events were reported.

Conclusions: This systematic review and meta-analysis indicated CPMs might be effective for the prevention and treatment of radiotherapy and chemotherapy-induced oral mucositis through reducing the prevalence, decreasing the occurrence of severe types, alleviating the symptoms, and promoting the healing of ulceration. However, due to the limited number of eligible studies and the publication bias, more high-quality, double-blinded, placebo-controlled RCTs are still needed in future research.

Systematic Review Registration: [https://inplasy.com/], identifier [INPLASY2021100100].
Noncoding RNAs in the Glycolysis of Ovarian Cancer
Authors: Zhang Chunmei , Liu Ning
Published: March 2022

Energy metabolism reprogramming is the characteristic feature of tumors. The tumorigenesis, metastasis, and drug resistance of ovarian cancer (OC) is dependent on energy metabolism. Even under adequate oxygen conditions, OC cells tend to convert glucose to lactate, and glycolysis can rapidly produce ATP to meet their metabolic energy needs. Non-coding RNAs (ncRNAs) interact directly with DNA, RNA, and proteins to function as an essential regulatory in gene expression and tumor pathology. Studies have shown that ncRNAs regulate the process of glycolysis by interacting with the predominant glycolysis enzyme and cellular signaling pathway, participating in tumorigenesis and progression. This review summarizes the mechanism of ncRNAs regulation in glycolysis in OC and investigates potential therapeutic targets.
A Closed-Loop Modeling Framework for Cardiac-to-Coronary Coupling
Authors: Munneke Anneloes G. , Lumens Joost , Arts Theo , Delhaas Tammo
Published: March 2022

The mechanisms by which cardiac mechanics effect coronary perfusion (cardiac-to-coronary coupling) remain incompletely understood. Several coronary models have been proposed to deepen our understanding of coronary hemodynamics, but possibilities for in-depth studies on cardiac-to-coronary coupling are limited as mechanical properties like myocardial stress and strain are most often neglected. To overcome this limitation, a mathematical model of coronary mechanics and hemodynamics was implemented in the previously published multi-scale CircAdapt model of the closed-loop cardiovascular system. The coronary model consisted of a relatively simple one-dimensional network of the major conduit arteries and veins as well as a lumped parameter model with three transmural layers for the microcirculation. Intramyocardial pressure was assumed to arise from transmission of ventricular cavity pressure into the myocardial wall as well as myocardial stiffness, based on global pump mechanics and local myofiber mechanics. Model-predicted waveforms of global epicardial flow velocity, as well as of intramyocardial flow and diameter were qualitatively and quantitatively compared with reported data. Versatility of the model was demonstrated in a case study of aortic valve stenosis. The reference simulation correctly described the phasic pattern of coronary flow velocity, arterial flow impediment, and intramyocardial differences in coronary flow and diameter. Predicted retrograde flow during early systole in aortic valve stenosis was in agreement with measurements obtained in patients. In conclusion, we presented a powerful multi-scale modeling framework that enables realistic simulation of coronary mechanics and hemodynamics. This modeling framework can be used as a research platform for in-depth studies of cardiac-to-coronary coupling, enabling study of the effect of abnormal myocardial tissue properties on coronary hemodynamics.
Analysis of WRKY Resistance Gene Family in Boehmeria nivea (L.) Gaudich: Crosstalk Mechanisms of Secondary Cell Wall Thickening and Cadmium Stress
Authors: Feng Xinkang , Abubakar Aminu Shehu , Yu Chunming , Zhu Aiguo , Chen Jikang , Chen Kunmei , Gao Gang , Wang Xiaofei , Mou Pan , Shao Deyi , Chen Ping
Published: March 2022

A total of 60 WRKY family genes of ramie were identified in the ramie. The genes were unevenly distributed across 14 chromosomes in the specie and highly concentrated (72%) in the distal telomeric region. Phylogenetic analysis placed these genes into seven distinct subfamilies groups: I, II (a, b, c, d, e), and III, with group IIc containing only the variant of heptapetide sequence (WRKYGKK). Segmental duplication events (41.7%) was found to be the main driver of BnGWRKY evolution. Thirty eight from among the genes showed collinear relationships with WRKY genes from Arabidopsis thaliana, Cannabis sativa, Oryza sativa, and Zea mays. The number and density of stress and hormone responsives cis-acting elements were comparably higher than other elements, with abundant ARE and rare LTR cis-acting elements indicating the long-standing adaptability of ramie to its natural environment. GO and KEGG enrichment analysis of the WRKY target genes revealed their involvement in response to stimuli, immune system processes, transporter protein activity and antioxidant activity. Expression analysis show that most WRKYs were activated by the cadmium stress, more especially the BnGWRKY2, BnGWRKY15, BnGWRKY20, BnGWRKY50 and BnGWRKY58. Combining transcriptome, orthologous gene relationships and qPCR result, we established the possible involvement of BnGWRKY50 and BnGWRKY58 in crosstalk mechanism between secondary cell wall thickening and Cd2+ stress. This provided information into the role of BnGWRKY proteins in ramie secondary wall development and cadmium stress response to, and could serve as basis for improvement of the ramie.
Community Wellbeing Under China-Pakistan Economic Corridor: Role of Social, Economic, Cultural, and Educational Factors in Improving Residents’ Quality of Life
Authors: Aman Jaffar , Abbas Jaffar , Shi Guoqing , Ain Noor Ul , Gu Likun
Published: March 2022

This present article explores the effects of cultural value, economic prosperity, and community mental wellbeing through multi-sectoral infrastructure growth projects under the Belt and Road Initiative. The implications of the social exchange theory are applied to observe the support of the local community for the China-Pakistan Economic Corridor (CPEC). This study explores the CPEC initiative, it’s direct social, cultural, economic development, and risk of environmental factors that affect residents’ lives and the local community’s wellbeing. CPEC is a multibillion-dollar project to uplift economic growth and free trade between Pakistan, China, and other regional stakeholders. Although CPEC is still in its initial phases with partial startups, policymakers and government officials claim this mega project as a “game-changer” in the region, mainly for Pakistan and China. This gigantic project offers the significant potential to generate business slews and employment opportunities with international outreach. Due to the term’s newness, numerous studies have recently explored the macro and microeconomic benefits of the CPEC initiatives; still, these projects are theoretical. The existing literature insufficiently explored how helpful CPEC would be to a specific group and how residents perceive its advantages. This study fills in the literature gaps and explores the likely advantageous potential of the CPEC for the regional states. The study applied a convenient sampling technique for the data collection process. It used a mixed-method approach to gain scientific results, with a standardized questionnaire survey of 459 people (300 men and 159 women) from five major cities of Pakistan. The study results designate that residents believe that CPEC infrastructure projects will significantly improve residents’ life quality through more job openings and community poverty reduction. Still, they raised their concerns regarding environmental protection issues in the region. The findings specified that residents had an optimistic approach to better educational productivity by adopting environment-oriented policies. Policymakers should establish new CPEC study centers in different areas, and investors should be encouraged to participate in the industrial sector. Officials can overwhelm community worries about environmental degradation. Government officials in both countries can utilize the findings to raise public awareness about CPEC’s social, economic, cultural, mental wellbeing, and ecological implications.
Native Word Order Processing Is Not Uniform: An ERP Study of Verb-Second Word Order
Authors: Sayehli Susan , Gullberg Marianne , Newman Aaron J. , Andersson Annika
Published: March 2022

Studies of native syntactic processing often target phrase structure violations that do not occur in natural production. In contrast, this study examines how variation in basic word order is processed, looking specifically at structures traditionally labelled as violations but that do occur naturally. We examined Swedish verb-second (V2) and verb-third (V3) word order processing in adult native Swedish speakers, manipulating sentence-initial adverbials (temporal idag ‘today’, spatial hemma ‘at home’ and sentential kanske ‘maybe’) in acceptability judgements, in simultaneously recorded event-related potentials (ERP) to visually presented sentences and in a written sentence completion task. An initial corpus study showed that the adverbials differ in frequency in fronted position (idag > kanske > hemma), and although all occur mainly with V2 word order, kanske occurs more frequently with V3 in natural production than both idag and hemma. The experimental results reflected these patterns such that V2 sentences were overall more frequently produced and were deemed more acceptable than V3 sentences. The ERP results consisted of a biphasic N400/P600 response to V3 word order that indicated effects of word retrieval and sentence reanalysis. We also found consistent effects of adverbials. As predicted, V3 was produced more frequently and judged as more acceptable in Kanske sentences than in sentences with the other two adverbials. The ERP analyses showed stronger effects for idag and hemma with V3, especially regarding the P600. The results suggest that the naturally occurring word order ‘violation’, V3 with kanske, is processed differently than V3 with other adverbials where the V2 norm is stronger. Moreover, these patterns are related to individuals’ own production patterns. Overall, the results suggest a more varied native word order processing than previously reported.