bluuebunny/crossref_metadata_2025 huggingface dataset:
Gas–thermal–solid coupling analysis of a hypersonic inflatable reentry and descent system
Authors: Cao Xu , Xu Rui , Yu Li , Zhao Xiaoshun , Wang Qi
Published: March 2023

Hypersonic reentry has a severe flight environment during spacecraft return. To analyze the influence of pneumatic loads on the flexible structure under the extreme load condition during the deceleration process of inflatable reentry and descent system, fluid–and thermal–solid couplings have been studied. In addition, the stress and structural deformation distributions and the temperature distribution of each functional layer of the flexible thermal protection system were obtained in this study. The influence of flight conditions and structural parameter changes on inflatable structure performance was studied, and the transient response mechanism of the pneumatic load to the inflatable structure was revealed. Ballistic analysis combined with engineering algorithm was used to predicted the flight envelope. The fluid-solid thermal coupling method in Workbench is utilized to realize the real-time transfer of aerodynamic and thermal loads to flexible structures. And the loose coupling method was applied to carried out the one-way transfer of aerodynamic load and thermal load to the surface of flexible structure. The results showed that the mechanical–thermal–structural coupling analysis method could predict the mechanical properties of flexible inflatable deceleration structures, which can provide references for the aerodynamic configuration and thermal protection design under extreme flight conditions.
The lymphatic vasculature in lung function and respiratory disease
Authors: Trivedi Anjali , Reed Hasina Outtz
Published: March 2023

The lymphatic vasculature maintains tissue homeostasis via fluid drainage in the form of lymph and immune surveillance due to migration of leukocytes through the lymphatics to the draining lymph nodes. Lymphatic endothelial cells (LECs) form the lymphatic vessels and lymph node sinuses and are key players in shaping immune responses and tolerance. In the healthy lung, the vast majority of lymphatic vessels are found along the bronchovascular structures, in the interlobular septa, and in the subpleural space. Previous studies in both mice and humans have shown that the lymphatics are necessary for lung function from the neonatal period through adulthood. Furthermore, changes in the lymphatic vasculature are observed in nearly all respiratory diseases in which they have been analyzed. Recent work has pointed to a causative role for lymphatic dysfunction in the initiation and progression of lung disease, indicating that these vessels may be active players in pathologic processes in the lung. However, the mechanisms by which defects in lung lymphatic function are pathogenic are understudied, leaving many unanswered questions. A more comprehensive understanding of the mechanistic role of morphological, functional, and molecular changes in the lung lymphatic endothelium in respiratory diseases is a promising area of research that is likely to lead to novel therapeutic targets. In this review, we will discuss our current knowledge of the structure and function of the lung lymphatics and the role of these vessels in lung homeostasis and respiratory disease.
Antibacterial properties of antimicrobial peptide HHC36 modified polyetheretherketone
Authors: Gao Weijia , Han Xiao , Sun Duo , Li Yongli , Liu Xiaoli , Yang Shihui , Zhou Zhe , Qi Yuanzheng , Jiao Junjie , Zhao Jinghui
Published: March 2023

Introduction

Polyetheretherketone (PEEK) is considered to be a new type of orthopedic implant material due to its mechanical properties and biocompatibility. It is becoming a replacement for titanium (Ti) due to its near-human-cortical transmission and modulus of elasticity. However, its clinical application is limited because of its biological inertia and susceptibility to bacterial infection during implantation. To solve this problem, there is an urgent need to improve the antibacterial properties of PEEK implants.

Methods

In this work, we fixed antimicrobial peptide HHC36 on the 3D porous structure of sulfonated PEEK (SPEEK) by a simple solvent evaporation method (HSPEEK), and carried out characterization tests. We evaluated the antibacterial properties and cytocompatibility of the samples in vitro. In addition, we evaluated the anti-infection property and biocompatibility of the samples in vivo by establishing a rat subcutaneous infection model.

Results

The characterization test results showed that HHC36 was successfully fixed on the surface of SPEEK and released slowly for 10 days. The results of antibacterial experiments in vitro showed that HSPEEK could reduce the survival rate of free bacteria, inhibit the growth of bacteria around the sample, and inhibit the formation of biofilm on the sample surface. The cytocompatibility test in vitro showed that the sample had no significant effect on the proliferation and viability of L929 cells and had no hemolytic activity on rabbit erythrocytes. In vivo experiments, HSPEEK can significantly reduce the bacterial survival rate on the sample surface and the inflammatory reaction in the soft tissue around the sample.

Discussion

We successfully loaded HHC36 onto the surface of SPEEK through a simple solvent evaporation method. The sample has excellent antibacterial properties and good cell compatibility, which can significantly reduce the bacterial survival rate and inflammatory reaction in vivo. The above results indicated that we successfully improved the antibacterial property of PEEK by a simple modification strategy, making it a promising material for anti-infection orthopedic implants.
Different and unified responses of soil bacterial and fungal community composition and predicted functional potential to 3 years’ drought stress in a semiarid alpine grassland
Authors: Wan Qian , Li Lei , Liu Bo , Zhang Zhihao , Liu Yalan , Xie Mingyu
Published: March 2023

Introduction

Soil microbial communities are key to functional processes in terrestrial ecosystems, and they serve as an important indicator of grasslands status. However, the responses of soil microbial communities and functional potential to drought stress in semiarid alpine grasslands remain unclear.

Methods

Here, a field experiment was conducted under ambient precipitation as a control, −20% and −40% of precipitation to explore the responses of soil microbial diversity, community composition, and predicted functional potential to drought stress in a semiarid alpine grassland located in the northwest of China. Moreover, 16S rRNA gene and ITS sequencing were used to detect bacterial and fungal communities, and the PICRUST and FUNGuild databases were used to predict bacterial and fungal functional groups.

Results

Results showed drought stress substantially changes the community diversity of bacteria and fungi, among which the bacteria community is more sensitive to drought stress than fungi, indicating that the diversity or structure of soil bacteria community could serve as an indicator of alpine grasslands status. However, the fungal community still has difficulty maintaining resistance under excessive drought stress. Our paper also highlighted that soil moisture content, plant diversity (Shannon Wiener, Pieiou, and Simpson), and soil organic matter are the main drivers affecting soil bacterial and fungal community composition and predicted functional potential. Notably, the soil microbial functional potential could be predictable through taxonomic community profiles.

Conclusion

Our research provides insight for exploring the mechanisms of microbial community composition and functional response to climate change (longer drought) in a semiarid alpine grassland.
Impact of intercropping grass on the soil rhizosphere microbial community and soil ecosystem function in a walnut orchard
Authors: Wang Changxi , Liang Qiang , Liu Jianning , Zhou Rui , Lang Xinya , Xu Shengyi , Li Xichen , Gong Andi , Mu Yutian , Fang Hongcheng , Yang Ke Qiang
Published: March 2023

The intercropping of grass in orchards has beneficial effects on soil properties and soil microbial communities and is an important soil management measure for improving orchard productivity and land-use efficiency. However, few studies have explored the effects of grass intercropping on rhizosphere microorganisms in walnut orchards. In this study, we explored the microbial communities of clear tillage (CT), walnut/ryegrass (Lolium perenne L.) (Lp), and walnut/hairy vetch (Vicia villosa Roth.) (Vv) intercropping system using MiSeq sequencing and metagenomic sequencing. The results revealed that the composition and structure of the soil bacterial community changed significantly with walnut/Vv intercropping compared to CT and walnut/Lp intercropping. Moreover, the walnut/hairy vetch intercropping system had the most complex connections between bacterial taxa. In addition, we found that the soil microorganisms of walnut/Vv intercropping had a higher potential for nitrogen cycling and carbohydrate metabolism, which may be related to the functions of Burkholderia, Rhodopseudomonas, Pseudomonas, Agrobacterium, Paraburkholderia, and Flavobacterium. Overall, this study provided a theoretical basis for understanding the microbial communities associated with grass intercropping in walnut orchards, providing better guidance for the management of walnut orchards.
Bidirectional Mendelian randomization study of psychiatric disorders and Parkinson’s disease
Authors: Wu Qi , Liu Shulin , Huang Xiurong , Liu Jiabin , Wang Yige , Xiang Yaqing , Tang Xuxiong , Xu Qian , Yan Xinxiang , Tang Beisha , Guo Jifeng
Published: March 2023

Introduction

Although the relationship between psychiatric disorders and Parkinson’s disease (PD) has attracted continuous research attention, the causal linkage between them has not reached a definite conclusion.

Methods

To identify the causal relationship between psychiatric disorders and PD, we used public summary-level data from the most recent and largest genome-wide association studies (GWASs) on psychiatric disorders and PD to conduct a bidirectional two-sample Mendelian randomization (MR). We applied stringent control steps in instrumental variable selection using the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) method to rule out pleiotropy. The inverse-variance weighted (IVW) method was used to identify the causal relationship between psychiatric disorders and PD. Multiple MR analysis methods, including MR-Egger, weighted-median, and leave-one-out analyses, were used for sensitivity analysis, followed by heterogeneity tests. Further validation and reverse MR analyses were conducted to strengthen the results of the forward MR analysis.

Results

The lack of sufficient estimation results could suggest a causal relationship between psychiatric disorders and PD in the forward MR analysis. However, the subsequent reverse MR analysis detected a causal relationship between PD and bipolar disorder (IVW: odds ratios [OR] =1.053, 95% confidence interval [CI] =1.02–1.09, p = 0.001). Further analysis demonstrated a causal relationship between genetically predicted PD and the risk of bipolar disorder subtype. No pleiotropy or heterogeneity was detected in the analyses.

Discussion

Our study suggested that while psychiatric disorders and traits might play various roles in the risk of developing PD, PD might also be involved in the risk of developing psychiatric disorders.
Frameshift mutation in SQSTM1 causes proximal myopathy with rimmed vacuoles: A case report
Authors: Wu Rui , Shao Sai , Yin Ling , Deng Jianwen , Guo Shougang , Lu Lin
Published: March 2023

p62/Sequestosome-1 (SQSTM1) is a stress-inducible scaffold protein involved in multiple cellular processes, including apoptosis, inflammation, cell survival, and selective autophagy. SQSTM1 mutations are associated with a spectrum of multisystem proteinopathy, including Paget disease of the bone, amyotrophic lateral sclerosis, frontotemporal dementia, and distal myopathy with rimmed vacuoles (MRV). Herein, we report a new phenotype of SQSTM1-associated proteinopathy, a novel frameshift mutation in SQSTM1 causing proximal MRV. A 44-year-old Chinese patient presented with progressive limb–girdle weakness. She had asymmetric proximal limb weakness and myopathic features on electromyography. The magnetic resonance images showed fatty infiltration into muscles, predominantly in the thighs and medial gastrocnemius, sparing the tibialis anterior. Muscle histopathology revealed abnormal protein deposition, p62/SQSTM1-positive inclusions, and rimmed vacuoles. Next-generation sequencing showed a novel pathogenic SQSTM1 frameshift mutation, c.542_549delACAGCCGC (p. H181Lfs*66). We expanded the pathogenic genotype of SQSTM1 to include a new, related phenotype: proximal MRV. We suggest that SQSTM1 variations should be screened in cases of proximal MRV.
How often is occult atrial fibrillation in cryptogenic stroke causal vs. incidental? A meta-analysis
Authors: Chaisinanunkul Napasri , Khurshid Shaan , Buck Brian H. , Rabinstein Alejandro A. , Anderson Christopher D. , Hill Michael D. , Fugate Jennifer E. , Saver Jeffrey L.
Published: March 2023

Introduction

Long-term cardiac monitoring studies have unveiled low-burden, occult atrial fibrillation (AF) in some patients with otherwise cryptogenic stroke (CS), but occult AF is also found in some individuals without a stroke history and in patients with stroke of a known cause (KS). Clinical management would be aided by estimates of how often occult AF in a patient with CS is causal vs. incidental.

Methods

Through a systematic search, we identified all case–control and cohort studies applying identical long-term monitoring techniques to both patients with CS and KS. We performed a random-effects meta-analysis across these studies to determine the best estimate of the differential frequency of occult AF in CS and KS among all patients and across age subgroups. We then applied Bayes' theorem to determine the probability that occult AF is causal or incidental.

Results

The systematic search identified three case–control and cohort studies enrolling 560 patients (315 CS, 245 KS). Methods of long-term monitoring were implantable loop recorder in 31.0%, extended external monitoring in 67.9%, and both in 1.2%. Crude cumulative rates of AF detection were CS 47/315 (14.9%) vs. KS 23/246 (9.3%). In the formal meta-analysis, the summary odds ratio for occult AF in CS vs. KS in all patients was 1.80 (95% CI, 1.05–3.07), p = 0.03. With the application of Bayes' theorem, the corresponding probabilities indicated that, when present, occult AF in patients with CS is causal in 41.2% (95% CI, 15.5–77.7%) of patients. Analyses stratified by age suggested that detected occult AF in patients with CS was causal in 62.3% (95 CI, 0–87.1%) of patients under the age of 65 years and 28.5% (95 CI, 0–63.7%) of patients aged 65 years and older but estimates had limited precision.

Conclusion

Current evidence is preliminary, but it indicates that in cryptogenic stroke when occult AF is found, it is causal in about 41.2% of patients. These findings suggest that anticoagulation therapy may be beneficial to prevent recurrent stroke in a substantial proportion of patients with CS found to have occult AF.
Neuro-oncological augmented reality planning for intracranial tumor resection
Authors: Van Gestel Frederick , Frantz Taylor , Buyck Felix , Geens Wietse , Neuville Quentin , Bruneau Michaël , Jansen Bart , Scheerlinck Thierry , Vandemeulebroucke Jef , Duerinck Johnny
Published: March 2023

Background

Before starting surgery for the resection of an intracranial tumor, its outlines are typically marked on the skin of the patient. This allows for the planning of the optimal skin incision, craniotomy, and angle of approach. Conventionally, the surgeon determines tumor borders using neuronavigation with a tracked pointer. However, interpretation errors can lead to important deviations, especially for deep-seated tumors, potentially resulting in a suboptimal approach with incomplete exposure. Augmented reality (AR) allows displaying of the tumor and critical structures directly on the patient, which can simplify and improve surgical preparation.

Methods

We developed an AR-based workflow for intracranial tumor resection planning deployed on the Microsoft HoloLens II, which exploits the built-in infrared-camera for tracking the patient. We initially performed a phantom study to assess the accuracy of the registration and tracking. Following this, we evaluated the AR-based planning step in a prospective clinical study for patients undergoing resection of a brain tumor. This planning step was performed by 12 surgeons and trainees with varying degrees of experience. After patient registration, tumor outlines were marked on the patient's skin by different investigators, consecutively using a conventional neuronavigation system and an AR-based system. Their performance in both registration and delineation was measured in terms of accuracy and duration and compared.

Results

During phantom testing, registration errors remained below 2.0 mm and 2.0° for both AR-based navigation and conventional neuronavigation, with no significant difference between both systems. In the prospective clinical trial, 20 patients underwent tumor resection planning. Registration accuracy was independent of user experience for both AR-based navigation and the commercial neuronavigation system. AR-guided tumor delineation was deemed superior in 65% of cases, equally good in 30% of cases, and inferior in 5% of cases when compared to the conventional navigation system. The overall planning time (AR = 119 ± 44 s, conventional = 187 ± 56 s) was significantly reduced through the adoption of the AR workflow (p < 0.001), with an average time reduction of 39%.

Conclusion

By providing a more intuitive visualization of relevant data to the surgeon, AR navigation provides an accurate method for tumor resection planning that is quicker and more intuitive than conventional neuronavigation. Further research should focus on intraoperative implementations.
Developmental changes in brain activity of heterozygous Scn1a knockout rats
Authors: Tahara Mayu , Higurashi Norimichi , Hata Junichi , Nishikawa Masako , Ito Ken , Hirose Shinichi , Kaneko Takehito , Mashimo Tomoji , Sakuma Tetsushi , Yamamoto Takashi , Okano Hirotaka James
Published: March 2023

Introduction

Dravet syndrome (DS) is an infantile-onset developmental and epileptic encephalopathy characterized by an age-dependent evolution of drug-resistant seizures and poor developmental outcomes. Functional impairment of gamma-aminobutyric acid (GABA)ergic interneurons due to loss-of-function mutation of SCN1A is currently considered the main pathogenesis. In this study, to better understand the age-dependent changes in the pathogenesis of DS, we characterized the activity of different brain regions in Scn1a knockout rats at each developmental stage.

Methods

We established an Scn1a knockout rat model and examined brain activity from postnatal day (P) 15 to 38 using a manganese-enhanced magnetic resonance imaging technique (MEMRI).

Results

Scn1a heterozygous knockout (Scn1a+/−) rats showed a reduced expression of voltage-gated sodium channel alpha subunit 1 protein in the brain and heat-induced seizures. Neural activity was significantly higher in widespread brain regions of Scn1a+/− rats than in wild-type rats from P19 to P22, but this difference did not persist thereafter. Bumetanide, a Na+-K+-2Cl− cotransporter 1 inhibitor, mitigated hyperactivity to the wild-type level, although no change was observed in the fourth postnatal week. Bumetanide also increased heat-induced seizure thresholds of Scn1a+/− rats at P21.

Conclusions

In Scn1a+/− rats, neural activity in widespread brain regions increased during the third postnatal week, corresponding to approximately 6 months of age in humans, when seizures most commonly develop in DS. In addition to impairment of GABAergic interneurons, the effects of bumetanide suggest a possible contribution of immature type A gamma-aminobutyric acid receptor signaling to transient hyperactivity and seizure susceptibility during the early stage of DS. This hypothesis should be addressed in the future. MEMRI is a potential technique for visualizing changes in basal brain activity in developmental and epileptic encephalopathies.
Motor imagery brain–computer interface rehabilitation system enhances upper limb performance and improves brain activity in stroke patients: A clinical study
Authors: Liao Wenzhe , Li Jiahao , Zhang Xuesong , Li Chen
Published: March 2023

This study compared the efficacy of Motor Imagery brain-computer interface (MI-BCI) combined with physiotherapy and physiotherapy alone in ischemic stroke before and after rehabilitation training. We wanted to explore whether the rehabilitation effect of MI-BCI is affected by the severity of the patient’s condition and whether MI-BCI was effective for all patients. Forty hospitalized patients with ischemic stroke with motor deficits participated in this study. The patients were divided into MI and control groups. Functional assessments were performed before and after rehabilitation training. The Fugl-Meyer Assessment (FMA) was used as the primary outcome measure, and its shoulder and elbow scores and wrist scores served as secondary outcome measures. The motor assessment scale (MAS) was used to assess motor function recovery. We used non-contrast CT (NCCT) to investigate the influence of different types of middle cerebral artery high-density signs on the prognosis of ischemic stroke. Brain topographic maps can directly reflect the neural activity of the brain, so we used them to detect changes in brain function and brain topological power response after stroke. Compared the MI group and control group after rehabilitation training, better functional outcome was observed after MI-BCI rehabilitation, including a significantly higher probability of achieving a relevant increase in the Total FMA scores (MI = 16.70 ± 12.79, control = 5.34 ± 10.48), FMA shoulder and elbow scores (MI = 12.56 ± 6.37, control = 2.45 ± 7.91), FMA wrist scores (MI = 11.01 ± 3.48, control = 3.36 ± 5.79), the MAS scores (MI = 3.62 ± 2.48, control = 1.85 ± 2.89), the NCCT (MI = 21.94 ± 2.37, control = 17.86 ± 3.55). The findings demonstrate that MI-BCI rehabilitation training could more effectively improve motor function after upper limb motor dysfunction after stroke compared with routine rehabilitation training, which verifies the feasibility of active induction of neural rehabilitation. The severity of the patient’s condition may affect the rehabilitation effect of the MI-BCI system.
A RUSBoosted tree method for k-complex detection using tunable Q-factor wavelet transform and multi-domain feature extraction
Authors: Li Yabing , Dong Xinglong
Published: March 2023

Background

K-complex detection traditionally relied on expert clinicians, which is time-consuming and onerous. Various automatic k-complex detection-based machine learning methods are presented. However, these methods always suffered from imbalanced datasets, which impede the subsequent processing steps.

New method

In this study, an efficient method for k-complex detection using electroencephalogram (EEG)-based multi-domain features extraction and selection method coupled with a RUSBoosted tree model is presented. EEG signals are first decomposed using a tunable Q-factor wavelet transform (TQWT). Then, multi-domain features based on TQWT are pulled out from TQWT sub-bands, and a self-adaptive feature set is obtained from a feature selection based on the consistency-based filter for the detection of k-complexes. Finally, the RUSBoosted tree model is used to perform k-complex detection.

Results

Experimental outcomes manifest the efficacy of our proposed scheme in terms of the average performance of recall measure, AUC, and F10-score. The proposed method yields 92.41 ± 7.47%, 95.4 ± 4.32%, and 83.13 ± 8.59% for k-complex detection in Scenario 1 and also achieves similar results in Scenario 2.

Comparison to state-of-the-art methods

The RUSBoosted tree model was compared with three other machine learning classifiers [i.e., linear discriminant analysis (LDA), logistic regression, and linear support vector machine (SVM)]. The performance based on the kappa coefficient, recall measure, and F10-score provided evidence that the proposed model surpassed other algorithms in the detection of the k-complexes, especially for the recall measure.

Conclusion

In summary, the RUSBoosted tree model presents a promising performance in dealing with highly imbalanced data. It can be an effective tool for doctors and neurologists to diagnose and treat sleep disorders.
Arginine vasopressin hormone receptor antagonists in experimental autoimmune encephalomyelitis rodent models: A new approach for human multiple sclerosis treatment
Authors: Calvillo-Robledo Argelia , Ramírez-Farías Cynthia , Valdez-Urias Fernando , Huerta-Carreón Erika P. , Quintanar-Stephano Andrés
Published: March 2023

Multiple sclerosis (MS) is a chronic demyelinating and neurodegenerative disease that affects the central nervous system. MS is a heterogeneous disorder of multiple factors that are mainly associated with the immune system including the breakdown of the blood-brain and spinal cord barriers induced by T cells, B cells, antigen presenting cells, and immune components such as chemokines and pro-inflammatory cytokines. The incidence of MS has been increasing worldwide recently, and most therapies related to its treatment are associated with the development of several secondary effects, such as headaches, hepatotoxicity, leukopenia, and some types of cancer; therefore, the search for an effective treatment is ongoing. The use of animal models of MS continues to be an important option for extrapolating new treatments. Experimental autoimmune encephalomyelitis (EAE) replicates the several pathophysiological features of MS development and clinical signs, to obtain a potential treatment for MS in humans and improve the disease prognosis. Currently, the exploration of neuro-immune-endocrine interactions represents a highlight of interest in the treatment of immune disorders. The arginine vasopressin hormone (AVP) is involved in the increase in blood−brain barrier permeability, inducing the development and aggressiveness of the disease in the EAE model, whereas its deficiency improves the clinical signs of the disease. Therefore, this present review discussed on the use of conivaptan a blocker of AVP receptors type 1a and type 2 (V1a and V2 AVP) in the modulation of immune response without completely depleting its activity, minimizing the adverse effects associated with the conventional therapies becoming a potential therapeutic target in the treatment of patients with multiple sclerosis.
Brain-machine interface based on transfer-learning for detecting the appearance of obstacles during exoskeleton-assisted walking
Authors: Quiles Vicente , Ferrero Laura , Iáñez Eduardo , Ortiz Mario , Gil-Agudo Ángel , Azorín José M.
Published: March 2023

Introduction

Brain-machine interfaces (BMIs) attempt to establish communication between the user and the device to be controlled. BMIs have great challenges to face in order to design a robust control in the real field of application. The artifacts, high volume of training data, and non-stationarity of the signal of EEG-based interfaces are challenges that classical processing techniques do not solve, showing certain shortcomings in the real-time domain. Recent advances in deep-learning techniques open a window of opportunity to solve some of these problems. In this work, an interface able to detect the evoked potential that occurs when a person intends to stop due to the appearance of an unexpected obstacle has been developed.

Material and methods

First, the interface was tested on a treadmill with five subjects, in which the user stopped when an obstacle appeared (simulated by a laser). The analysis is based on two consecutive convolutional networks: the first one to discern the intention to stop against normal walking and the second one to correct false detections of the previous one.

Results and discussion

The results were superior when using the methodology of the two consecutive networks vs. only the first one in a cross-validation pseudo-online analysis. The false positives per min (FP/min) decreased from 31.8 to 3.9 FP/min and the number of repetitions in which there were no false positives and true positives (TP) improved from 34.9% to 60.3% NOFP/TP. This methodology was tested in a closed-loop experiment with an exoskeleton, in which the brain-machine interface (BMI) detected an obstacle and sent the command to the exoskeleton to stop. This methodology was tested with three healthy subjects, and the online results were 3.8 FP/min and 49.3% NOFP/TP. To make this model feasible for non-able bodied patients with a reduced and manageable time frame, transfer-learning techniques were applied and validated in the previous tests, and were then applied to patients. The results for two incomplete Spinal Cord Injury (iSCI) patients were 37.9% NOFP/TP and 7.7 FP/min.
Dietary magnesium and calcium intake is associated with lower risk of hearing loss in older adults: A cross-sectional study of NHANES
Authors: Wei Xinmin
Published: March 2023

Aim

Dietary intake as a modifiable factor has been reported to be associated with hearing loss (HL). The relationship between magnesium (Mg) and calcium (Ca) as common dietary nutrients and HL in the elderly has rarely been reported. This study aimed to assess the association between Mg and Ca intake and HL in older adults.

Method

This cross-sectional study included participants aged ≥70 years from the National Health and Nutrition Examination Survey (NHANES) 2005–2006, 2009–2010, and 2017–2018. Outcomes were low-frequency [pure-tone averages (PTAs) at 500, 1000, and 2000 Hz >25 dB] and speech-frequency (PTAs at 500, 1000, 2000, and 4,000 Hz >25 dB) HL. Multivariate logistic analysis was utilized to explore the association between dietary Mg and Ca intake and their combined intake (Ca/Mg, Ca*Mg) and HL, and was described as odds ratio (OR) and 95% confidence interval (CI).

Results

A total of 1,858 participants were included, of which 1,052 (55.95%) had low-frequency HL and 1,349 (72.62%) had speech-frequency HL. Dietary Ca intakes [OR = 0.86, 95%CI: (0.74–0.99)] and Mg intakes [OR = 0.81, 95%CI: (0.68–0.95)] and Ca * Mg [OR = 0.12, 95%CI: (0.02–0.87)] were associated with lower odds of low-frequency HL after adjusting for confounders. Similar, dietary Ca intakes [OR = 0.85, 95%CI: (0.77–0.95)] and Mg intakes [OR = 0.78, 95%CI: (0.68–0.90)] and Ca * Mg [OR = 0.23, 95%CI: (0.05–0.78)] were related to lower odds of speech-frequency HL. For different levels of Mg and Ca intake, the combined intake of Ca (≥1,044 mg) and Mg (≥330 mg) was related to lower odds of low-frequency HL [OR = 0.02, 95%CI: (0.00–0.27)] and speech-frequency HL [OR = 0.44, 95%CI: (0.21–0.89)].

Conclusion

Dietary intakes of Mg and Ca were associated with lower odds of HL and are a promising intervention to be further explored in older adults with HL.
Role of prebiotic dietary fiber in periodontal disease: A systematic review of animal studies
Authors: Tailor Rohan , Medara Nidhi , Chopra Aditi , Swarnamali Hasinthi , Eberhard Joerg , Jayasinghe Thilini N.
Published: March 2023

Background

Periodontitis is a chronic inflammatory condition affecting the supporting structures of a tooth in the oral cavity. The relationship between dietary fiber and periodontitis is poorly understood. The objective of this systematic review is to investigate if an intake of dietary fiber modulates periodontal disease in animal models and any concomitant effects on systemic inflammation, microbiota and their metabolites.

Methods

Animal studies using periodontitis models with any form of fiber intervention were included. Studies with comorbidities that were mutually inclusive with periodontitis and animals with physiological conditions were excluded. Search strategy with MeSH and free-text search terms were finalized and performed on the 22nd of September 2021.CINAHL Complete, EMBASE, MEDLINE, SciVerse Scopus® and Web of Science Core Collection databases were used to identify studies. SYRCLE’s risk of bias tool and CAMARADES were used for quality assessment. Results were synthesized utilizing Covidence© web-based platform software to remove duplicates, and the remaining studies were manually filtered.

Results

A total of 7,141 articles were retrieved from all databases. Out of 24 full-text articles assessed for eligibility, four studies (n = 4) were included. Four studies involved the use of β-(1,3/1,6)-glucan (n = 3) and mannan oligosaccharide (n = 1) at differing dosages for different study durations. All studies utilized a ligature-induced model of periodontitis in rats, either Wistar (n = 3) or Sprague–Dawley (n = 1). A dose-dependent relationship between the increased fiber intake and decrease in alveolar bone loss and pro-inflammatory markers was observed.

Conclusion

The number of included studies is limited and narrow in scope. They highlight the importance of pre-clinical trials in this field with broader dietary fiber intervention groups before proceeding to clinical trials. The use of dietary fiber as an intervention shows promise in the reduction of inflammatory conditions like periodontitis. However, further research is required to delineate the relationship between diet and its effects on microbiota and their metabolites such as short chain fatty acids in animal models of periodontitis.
Comprehensive analysis of the FOXA1-related ceRNA network and identification of the MAGI2-AS3/DUSP2 axis as a prognostic biomarker in prostate cancer
Authors: Yang Guo , Chen Xiong , Quan Zhen , Liu Miao , Guo Yuan , Tang Yangbin , Peng Lang , Wang Leilei , Wu Yingying , Wu Xiaohou , Liu Jiayu , Zheng Yongbo
Published: March 2023

Background

Prostate cancer (PCa) is the second most common cause of cancer-related deaths in American men. Even though increasing evidence has disclosed the competitive endogenous RNA (ceRNA) regulatory networks among cancers, the complexity and behavior characteristics of the ceRNA network in PCa remain unclear. Our study aimed to investigate the forkhead box A1 (FOXA1)-related ceRNA regulatory network and ascertain potential prognostic markers associated with PCa.

Methods

RNA sequence profiles downloaded from The Cancer Genome Atlas (TCGA) were analyzed to recognize differentially expressed genes (DEGs) derived from tumor and non-tumor adjacent samples as well as FOXA1low and FOXA1high tumor samples. The enrichment analysis was conducted for the dysregulated mRNAs. The network for the differentially expressed long non-coding RNA (lncRNA)-associated ceRNAs was then established. Survival analysis and univariate Cox regression analysis were executed to determine independent prognostic RNAs associated with PCa. The correlation between DUSP2 and immune cell infiltration level was analyzed. Tissue and blood samples were collected to verify our network. Molecular experiments were performed to explore whether DUSP2 is involved in the development of PCa.

Results

A ceRNA network related to FOXA1 was constructed and comprised 18 lncRNAs, 5 miRNAs, and 44 mRNAs. The MAGI2-AS3~has-mir-106a/has-mir-204~DUSP2 ceRNA regulatory network relevant to the prognosis of PCa was obtained by analysis. We markedly distinguished the MAGI2-AS3/DUSP2 axis in the ceRNA. It will most likely become a clinical prognostic model and impact the changes in the tumor immune microenvironment of PCa. The abnormal MAGI2-AS3 expression level from the patients’ blood manifested that it would be a novel potential diagnostic biomarker for PCa. Moreover, down-expressed DUSP2 suppressed the proliferation and migration of PCa cells.

Conclusions

Our findings provide pivotal clues to understanding the role of the FOXA1-concerned ceRNA network in PCa. Simultaneously, this MAGI2-AS3/DUSP2 axis might be a new significant prognostic factor associated with the diagnosis and prognosis of PCa.
Case report: Germline RECQL mutation potentially involved in hereditary predisposition to acute leukemia
Authors: Yuan Wei , Shang Zhen , Shen Kefeng , Yu Qiuxia , Lv Qiuxia , Cao Yang , Wang Jue , Yang Yi
Published: March 2023

The pathogenesis of acute leukemia is still complex and vague. Most types of acute leukemia are related to somatic gene mutations, and familial incidence is rare. Here we report a case of familial leukemia. The proband presented to our hospital with vaginal bleeding and disseminated intravascular coagulation at the age of 42 and was diagnosed with acute promyelocytic leukemia with typical PML-RARα fusion gene caused by t(15;17)(q24;q21) translocation. By taking the history, we found that the patient’s second daughter had been diagnosed with B-cell acute leukemia with ETV6-RUNX1 fusion gene at age 6. Then we performed whole exome sequencing in peripheral blood mononuclear cells from these two patients at remission status and identified 8 shared germline gene mutations. Using functional annotation and Sanger sequencing validation, we finally focused on a single nucleotide variant in RecQ like helicase (RECQL), rs146924988, which was negative in the proband’s healthy eldest daughter. This gene variant potentially led to a relative lack of RECQL protein, disordered DNA repair and chromatin rearrangement, which may mediate the occurrence of fusion genes, as driving factors for leukemia. This study identified a novel possible leukemia-related germline gene variant and provided a new understanding for the screening and pathogenesis of hereditary predisposition syndromes.
The polymorphisms of ANXA6 influence head and neck cancer susceptibility in the Chinese Han population
Authors: Xiong Weihong , Li Zhumei , Zeng Xiangfa , Cui Jun , Cheng Zhiming , Yang Xiaoying , Ding Yipeng
Published: March 2023

Background

Head and neck cancer (HNC) is the sixth most common malignant tumor worldwide and imposes a serious economic burden on society and individuals. Annexin has been implicated in multiple functions which are essential in HNC development, including cell proliferation, apoptosis, metastasis, and invasion. This study focused on the linkage between ANXA6 variants and HNC susceptibility in Chinese people.

Methods

Eight SNPs in ANXA6 from 139 HNC patients and 135 healthy controls were genotyped by the Agena MassARRAY platform. The correlation of SNPs with HNC susceptibility was evaluated using odds ratio and 95% confidence interval calculated by logistic regression using PLINK 1.9.

Results

Overall analysis results demonstrated that rs4958897 was correlated with an increased HNC risk (allele: OR = 1.41, p = 0.049; dominant: OR = 1.69, p = 0.039), while rs11960458 was correlated with reduced HNC risk (OR = 0.54, p = 0.030). In age ≤ 53, rs4958897 was related to reduce HNC risk. In males, rs11960458 (OR = 0.50, p = 0.040) and rs13185706 (OR = 0.48, p = 0.043) were protective factors for HNC, but rs4346760 was a risk factor for HNC. Moreover, rs4346760, rs4958897, and rs3762993 were also correlated with increased nasopharyngeal carcinoma risk.

Conclusions

Our findings suggest that ANXA6 polymorphisms are linked to the susceptibility to HNC in the Chinese Han population, indicating that ANXA6 may serve as a potential biomarker for HNC prognosis and diagnosis.
The role of EphA2 in ADAM17- and ionizing radiation-enhanced lung cancer cell migration
Authors: Waller Verena , Tschanz Fabienne , Winkler Rona , Pruschy Martin
Published: March 2023

Purpose

Ionizing radiation (IR) enhances the migratory capacity of cancer cells. Here we investigate in non-small-cell-lung-cancer (NSCLC) cells a novel link between IR-enhanced ADAM17 activity and the non-canonical pathway of EphA2 in the cellular stress response to irradiation.

Methods

Cancer cell migration in dependence of IR, EphA2, and paracrine signaling mediated by ADAM17 was determined using transwell migration assays. Changes of EphA2 pS897 and mRNA expression levels upon different ADAM17-directed treatment strategies, including the small molecular inhibitor TMI-005, the monoclonal antibody MEDI3622, and shRNAs, were mechanistically investigated. ADAM17-mediated release and cleavage of the EphA2 ligand ephrin-A1 was measured using ELISA and an acellular cleavage assay.

Results

Irradiation with 5 Gy enhanced tumor cell migration of NSCLC NCI-H358 cells in dependence of EphA2. At the same time, IR increased growth factor-induced EphA2 S897 phosphorylation via auto- and paracrine signaling. Genetic and pharmaceutical downregulation of ADAM17 activity abrogated growth factor (e.g. amphiregulin) release, which reduced MAPK pathway-mediated EphA2 S897 phosphorylation in an auto- and paracrine way (non-canonical EphA2-pathway) in NCI-H358 and A549 cells. These signaling processes were associated with reduced cell migration towards conditioned media derived from ADAM17-deficient cells. Interestingly, ADAM17 inhibition with the small molecular inhibitor TMI-005 led to the internalization and proteasomal degradation of EphA2, which was rescued by amphiregulin or MG-132 treatment. In addition, ADAM17 inhibition also abrogated ephrin-A1 cleavage and thereby interfered with the canonical EphA2-pathway.

Conclusion

We identified ADAM17 and the receptor tyrosine kinase EphA2 as two important drivers for (IR-) induced NSCLC cell migration and described a unique interrelation between ADAM17 and EphA2. We demonstrated that ADAM17 influences both, EphA2 (pS897) and its GPI-anchored ligand ephrin-A1. Using different cellular and molecular readouts, we generated a comprehensive picture of how ADAM17 and IR influence the EphA2 canonical and non-canonical pathway in NSCLC cells.
Case report: Bullous pemphigoid associated with sintilimab therapy for pMMR/MSS colorectal cancer
Authors: Wang Ting , Shao Qianwen , Xiao Chunmei , Liu Lianke
Published: March 2023

Immunotherapy has become a very effective treatment for many cancers. It has a unique set of immune system-related adverse effects, collectively known as immune-related adverse events (irAEs). Skin toxicities are the most common irAEs, of which bullous pemphigoid, although rare, is potentially life-threatening and affects patients’ survival. In this article, we report the treatment of bullous pemphigoid caused by programmed cell death protein-1 (PD-1) in a case of proficient mismatch repair (pMMR)/microsatellite stable (MSS) colorectal cancer. No significant adverse effects were observed in the patient after methylprednisone was tapered to 4 mg twice a day. No new skin lesions occurred recently in the patient and the original skin lesions healed. In particular, the patient’s immunotherapy was not stopped and the best outcome was a partial remission of the disease, lasting for more than 8 months.
A novel immune-related model to predict prognosis and responsiveness to checkpoint and angiogenesis blockade therapy in advanced renal cancer
Authors: Chen Peng , Bi Feng , Tan Weili , Jian Lian , Yu Xiaoping
Published: March 2023

Background

Immune checkpoint blockade (ICB) and anti-angiogenic drug combination has prolonged the survival of patients with advanced renal cell carcinoma (RCC). However, not all patients receive clinical benefits from this intervention. In this study, we aimed to establish a promising immune-related prognostic model to stratify the patients responding to ICB and anti-angiogenic drug combination and facilitate the development of personalized therapies for patients with RCC.

Materials and methods

Based on clinical annotations and RNA-sequencing (RNA-seq) data of 407 patients with advanced RCC from the IMmotion151 cohort, nine immune-associated differentially expressed genes (DEGs) between responders and non-responders to atezolizumab (anti-programmed death-ligand 1 antibody) plus bevacizumab (anti-vascular endothelial growth factor antibody) treatment were identified via weighted gene co-expression network analysis. We also conducted single-sample gene set enrichment analysis to develop a novel immune-related risk score (IRS) model and further estimate the prognosis of patients with RCC by predicting their sensitivity to chemotherapy and responsiveness to immunotherapy. IRS model was further validated using the JAVELIN Renal 101 cohort, the E-MTAB-3218 cohort, the IMvigor210 and GSE78220 cohort. Predictive significance of the IRS model for advanced RCC was assessed using receiver operating characteristic curves.

Results

The IRS model was constructed using nine immune-associated DEGs: SPINK5, SEMA3E, ROBO2, BMP5, ORM1, CRP, CTSE, PMCH and CCL3L1. Advanced RCC patients with high IRS had a high risk of undesirable clinical outcomes (hazard ratio = 1.91; 95% confidence interval = 1.43–2.55; P < 0.0001). Transcriptome analysis revealed that the IRS-low group exhibited significantly high expression levels of CD8+ T effectors, antigen-processing machinery, and immune checkpoints, whereas the epithelial–mesenchymal transition pathway was enriched in the IRS-high group. IRS model effectively differentiated the responders from non-responders to ICB combined with angiogenesis blockade therapy or immunotherapy alone, with area under the curve values of 0.822 in the IMmotion151 cohort, 0.751 in the JAVELIN Renal 101 cohort, and 0.776 in the E-MTAB-3218 cohort.

Conclusion

IRS model is a reliable and robust immune signature that can be used for patient selection to optimize the efficacy of ICB plus anti-angiogenic drug therapies in patients with advanced RCC.
In vivo active-targeting fluorescence molecular imaging with adaptive background fluorescence subtraction
Authors: Vega Jorge D. , Hara Daiki , Schmidt Ryder M. , Abuhaija Marwan B. , Tao Wensi , Dogan Nesrin , Pollack Alan , Ford John C. , Shi Junwei
Published: March 2023

Using active tumor-targeting nanoparticles, fluorescence imaging can provide highly sensitive and specific tumor detection, and precisely guide radiation in translational radiotherapy study. However, the inevitable presence of non-specific nanoparticle uptake throughout the body can result in high levels of heterogeneous background fluorescence, which limits the detection sensitivity of fluorescence imaging and further complicates the early detection of small cancers. In this study, background fluorescence emanating from the baseline fluorophores was estimated from the distribution of excitation light transmitting through tissues, by using linear mean square error estimation. An adaptive masked-based background subtraction strategy was then implemented to selectively refine the background fluorescence subtraction. First, an in vivo experiment was performed on a mouse intratumorally injected with passively targeted fluorescent nanoparticles, to validate the reliability and robustness of the proposed method in a stringent situation wherein the target fluorescence was overlapped with the strong background. Then, we conducted in vivo studies on 10 mice which were inoculated with orthotopic breast tumors and intravenously injected with actively targeted fluorescent nanoparticles. Results demonstrated that active targeting combined with the proposed background subtraction method synergistically increased the accuracy of fluorescence molecular imaging, affording sensitive tumor detection.
FBXW7 attenuates tumor drug resistance and enhances the efficacy of immunotherapy
Authors: Chen Shimin , Lin Jichun , Zhao Jiaojiao , Lin Qian , Liu Jia , Wang Qiang , Mui Ryan , Ma Leina
Published: March 2023

FBXW7 (F-box and WD repeat domain containing 7) is a critical subunit of the Skp1-Cullin1-F-box protein (SCF), acting as an E3 ubiquitin ligase by ubiquitinating targeted protein. Through degradation of its substrates, FBXW7 plays a pivotal role in drug resistance in tumor cells and shows the potential to rescue the sensitivity of cancer cells to drug treatment. This explains why patients with higher FBXW7 levels exhibit higher survival times and more favorable prognosis. Furthermore, FBXW7 has been demonstrated to enhance the efficacy of immunotherapy by targeting the degradation of specific proteins, as compared to the inactivated form of FBXW7. Additionally, other F-box proteins have also shown the ability to conquer drug resistance in certain cancers. Overall, this review aims to explore the function of FBXW7 and its specific effects on drug resistance in cancer cells.