bluuebunny/crossref_metadata_2025 huggingface dataset:
Contraction and expansion dynamics: deciphering genomic underpinnings of growth rate and pathogenicity in Mycobacterium
Authors: Zhu Xiaoying , Lu Qunfeng , Li Yulei , Long Qinqin , Zhang Xinyu , Long Xidai , Cao Demin
Published: November 2023

Background

Mycobacterium bacteria, encompassing both slow growth (SGM) and rapid growth mycobacteria (RGM), along with true pathogenic (TP), opportunistic pathogenic (OP), and non-pathogenic (NP) types, exhibit diverse phenotypes. Yet, the genetic underpinnings of these variations remain elusive.

Methods

Here, We conducted a comprehensive comparative genomics study involving 53 Mycobacterium species to unveil the genomic drivers behind growth rate and pathogenicity disparities.

Results

Our core/pan-genome analysis highlighted 1,307 shared gene families, revealing an open pan-genome structure. A phylogenetic tree highlighted clear boundaries between SGM and RGM, as well as TP and other species. Gene family contraction emerged as the primary alteration associated with growth and pathogenicity transitions. Specifically, ABC transporters for amino acids and inorganic ions, along with quorum sensing genes, exhibited significant contractions in SGM species, potentially influencing their distinct traits. Conversely, TP strains displayed contraction in lipid and secondary metabolite biosynthesis and metabolism-related genes. Across the 53 species, we identified 26 core and 64 accessory virulence factors. Remarkably, TP and OP strains stood out for their expanded mycobactin biosynthesis and type VII secretion system gene families, pivotal for their pathogenicity.

Conclusion

Our findings underscore the importance of gene family contraction in nucleic acids, ions, and substance metabolism for host adaptation, while emphasizing the significance of virulence gene family expansion, including type VII secretion systems and mycobactin biosynthesis, in driving mycobacterial pathogenicity.
Mutation of self-binding sites in the promoter of the MrpC transcriptional regulator leads to asynchronous Myxococcus xanthus development
Authors: McLaughlin Maeve , Higgs Penelope I.
Published: November 2023

Introduction

MrpC, a member of the CRP/Fnr transcription factor superfamily, is necessary to induce and control the multicellular developmental program of the bacterium, Myxococcus xanthus. During development, certain cells in the population first swarm into haystack-shaped aggregates and then differentiate into environmentally resistant spores to form mature fruiting bodies (a specialized biofilm). mrpC transcriptional regulation is controlled by negative autoregulation (NAR).

Methods

Wild type and mutant mrpC promoter regions were fused to a fluorescent reporter to examine effects on mrpC expression in the population and in single cells in situ. Phenotypic consequences of the mutant mrpC promoter were assayed by deep convolution neural network analysis of developmental movies, sporulation efficiency assays, and anti-MrpC immunoblot. In situ analysis of single cell MrpC levels in distinct populations were assayed with an MrpC-mNeonGreen reporter.

Results

Disruption of MrpC binding sites within the mrpC promoter region led to increased and broadened distribution of mrpC expression levels between individual cells in the population. Expression of mrpC from the mutant promoter led to a striking phenotype in which cells lose synchronized transition from aggregation to sporulation. Instead, some cells abruptly exit aggregation centers and remain locked in a cohesive swarming state we termed developmental swarms, while the remaining cells transition to spores inside residual fruiting bodies. In situ examination of a fluorescent reporter for MrpC levels in developmental subpopulations demonstrated cells locked in the developmental swarms contained MrpC levels that do not reach the levels observed in fruiting bodies.

Discussion

Increased cell-to-cell variation in mrpC expression upon disruption of MrpC binding sites within its promoter is consistent with NAR motifs functioning to reducing noise. Noise reduction may be key to synchronized transition of cells in the aggregation state to the sporulation state. We hypothesize a novel subpopulation of cells trapped as developmental swarms arise from intermediate levels of MrpC that are sufficient to promote aggregation but insufficient to trigger sporulation. Failure to transition to higher levels of MrpC necessary to induce sporulation may indicate cells in developmental swarms lack an additional positive feedback signal required to boost MrpC levels.
Genetic diversity into a novel free-living species of Bradyrhizobium from contaminated freshwater sediment
Authors: Zhang Naxue , Jin Chun-Zhi , Zhuo Ye , Li Taihua , Jin Feng-Jie , Lee Hyung-Gwan , Jin Long
Published: November 2023

A free-living Bradyrhizobium strain isolated from a contaminated sediment sample collected at a water depth of 4 m from the Hongze Lake in China was characterized. Phylogenetic investigation of the 16S rRNA gene, concatenated housekeeping gene sequences, and phylogenomic analysis placed this strain in a lineage distinct from all previously described Bradyrhizobium species. The sequence similarities of the concatenated housekeeping genes support its distinctiveness with the type strains of the named species. The complete genome of strain S12-14-2 consists of a single chromosome of size 7.3M. The strain lacks both a symbiosis island and important nodulation genes. Based on the data presented here, the strain represents a new species, for which the name Bradyrhizobium roseus sp. nov. is proposed for the type strain S12-14-2T. Several functional differences between the isolate and other published genomes indicate that the genus Bradyrhizobium is extremely heterogeneous and has functions within the community, such as non-symbiotic nitrogen fixation. Functional denitrification and nitrogen fixation genes were identified on the genomes of strain S12-14-2T. Genes encoding proteins for sulfur oxidation, sulfonate transport, phosphonate degradation, and phosphonate production were also identified. Lastly, the B. roseus genome contained genes encoding ribulose 1,5-bisphosphate carboxylase/oxygenase, a trait that presumably enables autotrophic flexibility under varying environmental conditions. This study provides insights into the dynamics of a genome that could enhance our understanding of the metabolism and evolutionary characteristics of the genus Bradyrhizobium and a new genetic framework for future research.
Development of sensitizer peptide-fused endolysin Lys1S-L9P acting against multidrug-resistant gram-negative bacteria
Authors: Son Su Min , Kim Joonbeom , Ryu Sangryeol
Published: November 2023

The advent of multidrug-resistant (MDR) bacteria poses a major threat to public health, garnering attention to novel antibiotic replacements. Endolysin, a bacteriophage-derived cell wall-degrading enzyme, is a promising alternative to conventional antibiotics. However, it is challenging to control Gram-negative bacteria due to the presence of the outer membrane that shields the peptidoglycan layer from enzymatic degradation. To overcome this threshold, we constructed the fusion endolysin Lys1S-L9P by combining endolysin LysSPN1S with KL-L9P, a sensitizer peptide known to extend efficacy of antibiotics by perturbing the outer membrane of Gram-negative bacteria. In addition, we established a new endolysin purification procedure that increases solubility allowing a 4-fold increase in production yield of Lys1S-L9P. The sensitizer peptide-fused endolysin Lys1S-L9P exhibited high bactericidal effects against many MDR Gram-negative pathogens and was more effective in eradicating biofilms compared to LysSPN1S. Moreover, Lys1S-L9P showed potential for clinical use, maintaining stability at various storage temperatures without cytotoxicity against human cells. In the in vivo Galleria mellonella model, Lys1S-L9P demonstrated potent antibacterial activity against MDR Gram-negative bacteria without inducing any toxic activity. This study suggest that Lys1S-L9P could be a potential biocontrol agent to combat MDR Gram-negative bacteria.
A new research proposal to prevent hydrogen embrittlement for nuclear waste container by bacteria-a mini review
Authors: Zhang Qichao , Jiang Yishan , Zhao Xin , Duan Jizhou , Chen Luning , Xu Ying
Published: November 2023

A large amount of nuclear waste produced in the process of nuclear energy utilization has always been a key problem to be solved urgently for nuclear safety. At present, “deep geological disposal” is a feasible method and generally accepted by many countries. The oxygen content in the near field environment of the waste container will decrease to anaerobic conditions, and hydrogen will permeation into the internal materials of container for a long time. Hydrogen evolution corrosion may cause a risk of hydrogen embrittlement. The harm of hydrogen embrittlement in metal container is far more severe than predictable uniform corrosion. It is a research hotspot that the microorganisms impact on the corrosion behavior of container materials in the deep geological environment. Microbial corrosion in deep geological environments can be divided into two types: aerobic microbial corrosion and anaerobic microbial corrosion. There is a type of hydrogen consuming microorganism in the natural environment that uses the oxidation of hydrogen as the energy for its life activities. This provides a new approach for us to study reducing the hydrogen embrittlement sensitivity of nuclear waste container materials.
Development and preliminary validation of a virtual reality memory test for assessing visuospatial memory
Authors: Kim Ko Woon , Choi Jong Doo , Chin Juhee , Lee Byung Hwa , Choi Jee Hyun , Na Duk L.
Published: November 2023

Background

Visuospatial memory impairment is a common symptom of Alzheimer’s disease; however, conventional visuospatial memory tests are insufficient to fully reflect visuospatial memory impairment in daily life.

Methods

To address patients’ difficulties in locating and recalling misplaced objects, we introduced a novel visuospatial memory test, the Hidden Objects Test (HOT), conducted in a virtual environment. We categorized HOT scores into prospective memory, item free-recall, place free-recall, item recognition, and place-item matching scores. To validate the VR memory test, we compared HOT scores among individuals with Alzheimer’s disease (AD), amnestic mild cognitive impairment (aMCI), and normal controls (NC), and also compared these scores with those of conventional neuropsychological tests. We tracked the participants’ movement paths in the virtual environment and assessed basic features, such as total distance, duration, and speed. Additionally, we performed walking trajectory pattern mining such as outlier and stay-point detection.

Results

We designed and implemented the HOT to simulate a house’s living room and assess participants’ ability to locate hidden objects. Our preliminary results showed that the total HOT score differed among 17 patients with AD, 14 with aMCI, and 15 NC (p < 0.001). The total HOT score correlated positively with conventional memory test scores (p < 0.001). Walking trajectories showed that patients with AD and aMCI wandered rather than going straight to the hidden objects. In terms of basic features, the total duration was significantly greater in AD than in NC (p = 0.008). In terms of trajectory pattern mining, the number of outliers, which were over 95% of the estimated trajectory, was significantly higher in AD than in NC (p = 0.002). The number of stay points, an index in which participants stayed in the same position for more than 2 s, was significantly higher in patients with AD and aMCI compared with NC (AD vs. NC: p = 0.003, aMCI vs. NC: p = 0.019).

Conclusion

The HOT simulating real life showed potential as an ecologically valid test for assessing visuospatial memory function in daily life. Walking trajectory analysis suggested that patients with AD and aMCI wandered rather than going straight toward the hidden objects.
Integrating serum pharmacochemistry and network pharmacology to reveal the active constituents and mechanism of Corydalis Rhizoma in treating Alzheimer’s disease
Authors: Lyu Yan , Wang Yu , Guo Jianyou , Wang Yuqing , Lu Yifan , Hao Zhuangzhuang , Jiang Tingyue , Fan Wenxin , Li Yihua , Shi Jinli
Published: November 2023

Background

Alzheimer’s disease (AD) is a multifactorial neurodegenerative condition. The search for multi-target traditional Chinese medicines or ingredients for treating AD has attracted much attention. Corydalis rhizome (CR) is a traditional Chinese medicine. Its main components are alkaloids, which have therapeutic effects that can potentially be used for treating AD. However, no systematic study has been conducted to explore the anti-AD efficacy of CR, as well as its active compounds and mechanisms of action.

Objective

The present study aimed to clarify CR’s active constituents and its pharmacological mechanisms in treating AD.

Methods

A D-galactose & scopolamine hydrobromide-induced AD mouse model was used and CR was administered orally. The prototypical alkaloid components were identified in the serum. The core components, key targets, and possible mechanisms of action of these alkaloids were revealed through network pharmacology. Molecular docking of the key target was performed. Finally, the mechanism was validated by lipopolysaccharide (LPS)-induced activation of BV2 microglia.

Results

The results showed that CR improved anxiety-like behavior, spatial and non-spatial recognition, and memory capacity in AD mice. It also achieved synergistic AD treatment by modulating neurotransmitter levels, anti-neuroinflammation, and anti-oxidative stress. The core components that enhance CR’s efficacy in treating AD are protoberberine-type alkaloids. The CR may induce the polarization of LPS-activated BV2 microglia from phenotype M1 to M2. This is partially achieved by modulating the IL-6/JAK2/STAT3 signaling pathway, which could be the mechanism by which CR treats AD through anti-inflammation.

Conclusion

The present study provided a theoretical and experimental basis for the clinical application of CR in treating AD. It also provides information that aids the secondary development, and precise clinical use of CR.
Resveratrol ameliorates maternal immune activation-associated cognitive impairment in adult male offspring by relieving inflammation and improving synaptic dysfunction
Authors: Zhang Yue-Ming , Wei Ru-Meng , Zhang Meng-Ying , Zhang Kai-Xuan , Zhang Jing-Ya , Fang Shi-Kun , Ge Yi-Jun , Kong Xiao-Yi , Chen Gui-Hai , Li Xue-Yan
Published: November 2023

Maternal exposure to inflammation may represent a major risk factor for neuropsychiatric disorders with associated cognitive dysfunction in offspring in later life. Growing evidence has suggested that resveratrol exerts a beneficial effect on cognitive impairment via its anti-inflammatory and antioxidant properties and by ameliorating synaptic dysfunction. However, how resveratrol affects maternal immune activation-induced cognitive dysfunction and the underlying mechanisms are unclear. In the present study, pregnant dams were given an intraperitoneal injection of lipopolysaccharide (LPS; 50 μg/kg) on gestational day 15. Subsequently, the offspring mice were treated or not with resveratrol (40 mg/kg) from postnatal day (PND) 60 to PND 88. Male offspring were selected for the evaluation of cognitive function using the Morris water maze test. The hippocampal levels of pro-inflammatory cytokines were examined by ELISA. The mRNA and protein levels of sirtuin-1 (SIRT1), brain-derived neurotrophic factor (BDNF), postsynaptic density protein 95 (PSD-95), and synaptophysin (SYP) were determined by RT-qPCR and western blot, respectively. The results showed that male offspring mice exposed to LPS in utero exhibited learning and memory impairment. Additionally, the levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) were increased while those of SIRT1, BDNF, PSD-95, and SYP were decreased in male offspring of LPS-treated mothers. Treatment with resveratrol reversed cognitive impairment and attenuated the increase in the levels of pro-inflammatory cytokines induced by maternal immune activation in the offspring mice. Furthermore, resveratrol reversed the deleterious effects of maternal immune activation on SIRT1, BDNF, PSD-95, and SYP levels in the hippocampus. Collectively, our results suggested that resveratrol can effectively improve learning and memory impairment induced by maternal immune activation via the modulation of inflammation and synaptic dysfunction.
Voting based double-weighted deterministic extreme learning machine model and its application
Authors: Lu Rongbo , Luo Liang , Liao Bolin
Published: November 2023

This study introduces an intelligent learning model for classification tasks, termed the voting-based Double Pseudo-inverse Extreme Learning Machine (V-DPELM) model. Because the traditional method is affected by the weight of input layer and the bias of hidden layer, the number of hidden layer neurons is too large and the model performance is unstable. The V-DPELM model proposed in this paper can greatly alleviate the limitations of traditional models because of its direct determination of weight structure and voting mechanism strategy. Through extensive simulations on various real-world classification datasets, we observe a marked improvement in classification accuracy when comparing the V-DPELM algorithm to traditional V-ELM methods. Notably, when used for machine recognition classification of breast tumors, the V-DPELM method demonstrates superior classification accuracy, positioning it as a valuable tool in machine-assisted breast tumor diagnosis models.
Evaluation of gliovascular functions of AQP4 readthrough isoforms
Authors: Mueller Shayna M. , McFarland White Kelli , Fass Stuart B. , Chen Siyu , Shi Zhan , Ge Xia , Engelbach John A. , Gaines Seana H. , Bice Annie R. , Vasek Michael J. , Garbow Joel R. , Culver Joseph P. , Martinez-Lozada Zila , Cohen-Salmon Martine , Dougherty Joseph D. , Sapkota Darshan
Published: November 2023

Aquaporin-4 (AQP4) is a water channel protein that links the astrocytic endfeet to the blood-brain barrier (BBB) and regulates water and potassium homeostasis in the brain, as well as the glymphatic clearance of waste products that would otherwise potentiate neurological diseases. Recently, translational readthrough was shown to generate a C-terminally extended variant of AQP4, known as AQP4x, which preferentially localizes around the BBB through interaction with the scaffolding protein α-syntrophin, and loss of AQP4x disrupts waste clearance from the brain. To investigate the function of AQP4x, we generated a novel AQP4 mouse line (AllX) to increase relative levels of the readthrough variant above the ~15% of AQP4 in the brain of wild-type (WT) mice. We validated the line and assessed characteristics that are affected by the presence of AQP4x, including AQP4 and α-syntrophin localization, integrity of the BBB, and neurovascular coupling. We compared AllXHom and AllXHet mice to WT and to previously characterized AQP4 NoXHet and NoXHom mice, which cannot produce AQP4x. An increased dose of AQP4x enhanced perivascular localization of α-syntrophin and AQP4, while total protein expression of the two was unchanged. However, at 100% readthrough, AQP4x localization and the formation of higher order complexes were disrupted. Electron microscopy showed that overall blood vessel morphology was unchanged except for an increased proportion of endothelial cells with budding vesicles in NoXHom mice, which may correspond to a leakier BBB or altered efflux that was identified in NoX mice using MRI. These data demonstrate that AQP4x plays a small but measurable role in maintaining BBB integrity as well as recruiting structural and functional support proteins to the blood vessel. This also establishes a new set of genetic tools for quantitatively modulating AQP4x levels.
Enhanced representation learning with temporal coding in sparsely spiking neural networks
Authors: Fois Adrien , Girau Bernard
Published: November 2023

Current representation learning methods in Spiking Neural Networks (SNNs) rely on rate-based encoding, resulting in high spike counts, increased energy consumption, and slower information transmission. In contrast, our proposed method, Weight-Temporally Coded Representation Learning (W-TCRL), utilizes temporally coded inputs, leading to lower spike counts and improved efficiency. To address the challenge of extracting representations from a temporal code with low reconstruction error, we introduce a novel Spike-Timing-Dependent Plasticity (STDP) rule. This rule enables stable learning of relative latencies within the synaptic weight distribution and is locally implemented in space and time, making it compatible with neuromorphic processors. We evaluate the performance of W-TCRL on the MNIST and natural image datasets for image reconstruction tasks. Our results demonstrate relative improvements of 53% for MNIST and 75% for natural images in terms of reconstruction error compared to the SNN state of the art. Additionally, our method achieves significantly higher sparsity, up to 900 times greater, when compared to related work. These findings emphasize the efficacy of W-TCRL in leveraging temporal coding for enhanced representation learning in Spiking Neural Networks.
Epileptic focus localization using transfer learning on multi-modal EEG
Authors: Yang Yong , Li Feng , Luo Jing , Qin Xiaolin , Huang Dong
Published: November 2023

The standard treatments for epilepsy are drug therapy and surgical resection. However, around 1/3 of patients with intractable epilepsy are drug-resistant, requiring surgical resection of the epileptic focus. To address the issue of drug-resistant epileptic focus localization, we have proposed a transfer learning method on multi-modal EEG (iEEG and sEEG). A 10-fold cross-validation approach was applied to validate the performance of the pre-trained model on the Bern-Barcelona and Bonn datasets, achieving accuracy rates of 94.50 and 97.50%, respectively. The experimental results have demonstrated that the pre-trained model outperforms the competitive state-of-the-art baselines in terms of accuracy, sensitivity, and negative predictive value. Furthermore, we fine-tuned our pre-trained model using the epilepsy dataset from Chongqing Medical University and tested it using the leave-one-out cross-validation method, obtaining an impressive average accuracy of 90.15%. This method shows significant feature differences between epileptic and non-epileptic channels. By extracting data features using neural networks, accurate classification of epileptic and non-epileptic channels can be achieved. Therefore, the superior performance of the model has demonstrated that the proposed method is highly effective for localizing epileptic focus and can aid physicians in clinical localization diagnosis.
Electrophysiological neuromuscular alterations and severe fatigue predict long-term muscle weakness in survivors of COVID-19 acute respiratory distress syndrome
Authors: Benedini Marco , Cogliati Marta , Lulic-Kuryllo Tea , Peli Elena , Mombelli Stefano , Calza Stefano , Guarneri Bruno , Cudicio Alessandro , Rizzardi Andrea , Bertoni Michele , Gazzina Stefano , Renzi Stefania , Gitti Nicola , Rasulo Frank A. , Goffi Alberto , Pozzi Matteo , Orizio Claudio , Negro Francesco , Latronico Nicola , Piva Simone
Published: November 2023

Introduction

Long-term weakness is common in survivors of COVID-19-associated acute respiratory distress syndrome (CARDS). We longitudinally assessed the predictors of muscle weakness in patients evaluated 6 and 12 months after intensive care unit discharge with in-person visits.

Methods

Muscle strength was measured by isometric maximal voluntary contraction (MVC) of the tibialis anterior muscle. Candidate predictors of muscle weakness were follow-up time, sex, age, mechanical ventilation duration, use of steroids in the intensive care unit, the compound muscle action potential of the tibialis anterior muscle (CMAP-TA-S100), a 6-min walk test, severe fatigue, depression and anxiety, post-traumatic stress disorder, cognitive assessment, and body mass index. We also compared the clinical tools currently available for the evaluation of muscle strength (handgrip strength and Medical Research Council sum score) and electrical neuromuscular function (simplified peroneal nerve test [PENT]) with more objective and robust measures of force (MVC) and electrophysiological evaluation of the neuromuscular function of the tibialis anterior muscle (CMAP-TA-S100) for their essential role in ankle control.

Results

MVC improved at 12 months compared with 6 months. CMAP-TA-S100 (P = 0.016) and the presence of severe fatigue (P = 0.036) were independent predictors of MVC. MVC was strongly associated with handgrip strength, whereas CMAP-TA-S100 was strongly associated with PENT.

Discussion

Electrical neuromuscular abnormalities and severe fatigue are independently associated with reduced MVC and can be used to predict the risk of long-term muscle weakness in CARDS survivors.
MRI-based radiomics features uncover the micro-change of dorsal root ganglia lesion for patients with post-herpetic neuralgia
Authors: Cao Xueqin , Wen Donglin , Yu Shangchen , Zheng Hua , Wu Gang , Zhang Xianwei
Published: November 2023

Objective

To create and authenticate MRI-based radiomic signatures to identify dorsal root ganglia (DRG) lesions in post-herpetic neuralgia (PHN) patients generalizable and interpretable.

Method

This prospective diagnostic study was conducted between January 2021 and February 2022. Lesioned DRG in patients with PHN and normal DRG in age-, sex-, height-, and weight-matched healthy controls were selected for assessment and divided into two groups (8:2) randomly: training and testing sets. The least absolute shrinkage and selection operator algorithm was employed to generate feature signatures and construct a model, followed by the assessment of model efficacy using the area under the curve (AUC) of the receiver operating characteristic (ROC), as well as sensitivity and specificity metrics.

Results

The present investigation involved 30 patients diagnosed with postherpetic neuralgia (PHN), consisting of 18 males and 12 females (mean age 60.70 ± 10.18 years), as well as 30 healthy controls, comprising 18 males and 12 females (mean age 58.13 ± 10.54 years). A total of 98 DRG were randomly divided into two groups (8:2), namely a training set (n = 78) and a testing set (n = 20). Five radiomic features were chosen to construct the models. In the training dataset, the area under the curve (AUC) was 0.847, while the sensitivity and specificity were 71.79 and 97.44%, respectively. In the test dataset, the AUC was 0.87, and the sensitivity and specificity were 80.00 and 100.00%, respectively.

Conclusion

An MRI-based radiomic signatures model has the capacity to uncover the micro-change of damaged DRG in individuals afflicted with postherpetic neuralgia.
The influence of environmental risk factors in the development of ALS in the Mediterranean Island of Cyprus
Authors: Mitsi Ellie , Christodoulou Christiana C. , Nicolaou Paschalis , Christodoulou Kyproula , Zamba-Papanicolaou Eleni
Published: November 2023

Introduction

Amyotrophic lateral sclerosis (ALS) is a devastating, uniformly lethal degenerative disease of motor neurons, presenting with relentlessly progressive muscle atrophy and weakness. The etiology of ALS remains unexplained for over 85% of all cases, suggesting that besides the genetic basis of the disease, various environmental factors are implicated in the pathogenesis of ALS. This study aimed to investigate the contribution of known environmental risk factors of ALS in the Cypriot population.

Methods

We conducted a case–control study with a total of 56 ALS cases and 56 healthy gender/age-matched controls of Cypriot nationality. Demographic, lifestyle characteristics, medical conditions, and environmental exposures were collected through the use of a detailed questionnaire. Statistical analyses using the R programming language examined the association between the above environmental factors and ALS.

Results

A chi-square test analysis revealed a statistically significant (p = 0.000461) difference in smoking status between the two groups. In addition, univariate logistic regression analysis showed a statistically significant association between ALS cases for head trauma/injury (p = 0.0398) and exposure to chemicals (p = 0.00128), compared to controls.

Conclusion

This case–control investigation has shed some light on the epidemiological data of ALS in Cyprus, by identifying environmental determinants of ALS, such as smoking, head trauma, and chemical exposure, in the Cypriot population.
Neck stabilization through sensory integration of vestibular and visual motion cues
Authors: Happee Riender , Kotian Varun , De Winkel Ksander N.
Published: November 2023

Background

To counteract gravity, trunk motion, and other perturbations, the human head–neck system requires continuous muscular stabilization. In this study, we combine a musculoskeletal neck model with models of sensory integration (SI) to unravel the role of vestibular, visual, and muscle sensory cues in head–neck stabilization and relate SI conflicts and postural instability to motion sickness.

Method

A 3D multisegment neck model with 258 Hill-type muscle elements was extended with postural stabilization using SI of vestibular (semicircular and otolith) and visual (rotation rate, verticality, and yaw) cues using the multisensory observer model (MSOM) and the subjective vertical conflict model (SVC). Dynamic head–neck stabilization was studied using empirical datasets, including 6D trunk perturbations and a 4 m/s2 slalom drive inducing motion sickness.

Results

Recorded head translation and rotation are well matched when using all feedback loops with MSOM or SVC or assuming perfect perception. A basic version of the model, including muscle, but omitting vestibular and visual perception, shows that muscular feedback can stabilize the neck in all conditions. However, this model predicts excessive head rotations in conditions with trunk rotation and in the slalom. Adding feedback of head rotational velocity sensed by the semicircular canals effectively reduces head rotations at mid-frequencies. Realistic head rotations at low frequencies are obtained by adding vestibular and visual feedback of head rotation based on the MSOM or SVC model or assuming perfect perception. The MSOM with full vision well captures all conditions, whereas the MSOM excluding vision well captures all conditions without vision. The SVC provides two estimates of verticality, with a vestibular estimate SVCvest, which is highly effective in controlling head verticality, and an integrated vestibular/visual estimate SVCint which can complement SVCvest in conditions with vision. As expected, in the sickening drive, SI models imprecisely estimate verticality, resulting in sensory conflict and postural instability.

Conclusion

The results support the validity of SI models in postural stabilization, where both MSOM and SVC provide credible results. The results in the sickening drive show imprecise sensory integration to enlarge head motion. This uniquely links the sensory conflict theory and the postural instability theory in motion sickness causation.
Case report and literature review: exploration of molecular therapeutic targets in recurrent malignant meningioma through comprehensive genetic analysis with Todai OncoPanel
Authors: Ohara Kenta , Miyawaki Satoru , Nakatomi Hirofumi , Okano Atsushi , Teranishi Yu , Shinya Yuki , Ishigami Daiichiro , Hongo Hiroki , Takayanagi Shunsaku , Tanaka Shota , Shinozaki-Ushiku Aya , Kohsaka Shinji , Kage Hidenori , Oda Katsutoshi , Miyagawa Kiyoshi , Aburatani Hiroyuki , Mano Hiroyuki , Tatsuno Kenji , Saito Nobuhito
Published: November 2023

Background

Despite accumulating research on the molecular characteristics of meningiomas, no definitive molecularly targeted therapy for these tumors has been established to date. Molecular mechanisms underlying meningioma progression also remain unclear. Comprehensive genetic testing approaches can reveal actionable gene aberrations in meningiomas. However, there is still limited information on whether profiling the molecular status of subsequent recurrent meningiomas could influence the choice of molecular-targeted therapies.

Case presentation

We report a case of meningioma with malignant progression and multiple recurrences. We performed matched tumor pair analysis using the Todai OncoPanel to investigate the possibility of additional standard treatments. The loss of several chromosomal regions, including NF2 and CDKN2A, which is associated with aggressive meningiomas, was considered a significant driver event for malignant progression. Using additional matched tumor pair analysis, mutations in TRAF7, ARID1A, and ERBB3 were identified as subclonal driver events at the time of recurrence. No genetic aberrations were found for which evidence-based targeted therapy was applicable. We also reviewed previous reports of molecular therapies in meningioma to discuss issues with the current molecular testing approach.

Conclusion

Gene panel testing platforms such as the Todai OncoPanel represent a powerful approach to elucidate actionable genetic alterations in various types of tumors, although their use is still limited to the diagnosis and prediction of prognosis in meningiomas. To enable targeted molecular therapy informed by gene-panel testing, further studies including matched tumor pair analyses are required to understand the molecular characteristics of meningiomas and develop treatments based on genetic abnormalities.
Exploratory study of the acute and mid-term effects of using a novel dynamic meeting environment (Aeris®) on cognitive performance and neurophysiological responses
Authors: Ammar Achraf , Boujelbane Mohamed Ali , Simak Marvin Leonard , Fraile-Fuente Irene , Trabelsi Khaled , Bouaziz Bassem , Rizzi Nikolas , Schöllhorn Wolfgang I.
Published: November 2023

The purpose of the present study was to assess the acute and mid-term effects of the dynamic aeris®-meeting- environment on brain activity, cognitive performance, heart rate variability (HRV), sleepiness, mental workload (EEG-MWI), as well as local experienced discomfort (LED) in healthy adults. Twenty-four healthy adults (16 females, age: 25.2 ± 3.1 years old) were randomly assigned to either the control (i.e., conventional meeting environment, CG) or experimental (Aeris® dynamic meeting-environment, DG) group with a 1:1 allocation. Participants reported to the laboratory on two test sessions separated by a 2-week intervention period (5 meetings of 90 min each week). Spontaneous resting EEG and HRV activities, as well as attentional (D2-R test) and vigilance (PVT) cognitive performances, sleepiness perceptions, and EEG-MWI, were recorded at the beginning of each test session and immediately following the 90-min meeting. The LED was measured pre- and post-intervention. The changes (Δ) from pre- to post-90 min meeting and from pre- to post- intervention were computed to further examine the acute and mid-term effects, respectively. Compared to the CG, the DG showed higher Δ (pre-post 90 min-meeting) in fronto-central beta (z = −2.41, p = 0.016, d = 1.10) and gamma (z = −2.34, p = 0.019, d = 0.94) frequencies at post-intervention. From pre- to post-intervention, only the DG group showed a significant increase in fronto-central gamma response (Δ) to the meeting session (z = −2.09, p = 0.04, d = 1.08). The acute use of the Aeris®-meeting-environment during the 90-min meeting session seems to be supportive for (i) maintaining vigilance performance, as evidenced by the significant increase in N-lapses from pre- to post-90 min session only in the CG (p = 0.04, d = 0.99, Δ = 2.5 ± 3 lapses), and (ii) improving alertness, as evidenced by the lower sleepiness score (p = 0.05, d = −0.84) in DG compared to CG. The mid-term use of such an environment showed to blind the higher baseline values of EEG-MWI recorded in DG compared to CG (p = 0.01, d = 1.05) and may prevent lower-back discomfort (i.e., a significant increase only in CG with p = 0.05 and d = 0.78), suggesting a less mentally and physically exhausting meeting in this environment. There were no acute and/or mid-term effects of the dynamic meeting environment on any of the HRV parameters. These findings are of relevance in the field of neuroergonomics, as they give preliminary support to the advantages of meeting in a dynamic office compared to a static office environment.
Adaptive yoga versus low-impact exercise for adults with chronic acquired brain injury: a pilot randomized control trial protocol
Authors: Stephens Jaclyn A. , Hernandez-Sarabia Jesus A. , Sharp Julia L. , Leach Heather J. , Bell Christopher , Thomas Michael L. , Burzynska Agnieszka , Weaver Jennifer A. , Schmid Arlene A.
Published: November 2023

Background

Each year, millions of Americans sustain acquired brain injuries (ABI) which result in functional impairments, such as poor balance and autonomic nervous system (ANS) dysfunction. Although significant time and energy are dedicated to reducing functional impairment in acute phase of ABI, many individuals with chronic ABI have residual impairments that increase fall risk, decrease quality of life, and increase mortality. In previous work, we have found that yoga can improve balance in adults with chronic (i.e., ≥6 months post-injury) ABI. Moreover, yoga has been shown to improve ANS and brain function in healthy adults. Thus, adults with chronic ABI may show similar outcomes. This protocol details the methods used to examine the effects of a group yoga program, as compared to a group low-impact exercise, on primary and secondary outcomes in adults with chronic ABI.

Methods

This study is a single-blind randomized controlled trial comparing group yoga to group low-impact exercise. Participants must be ≥18 years old with chronic ABI and moderate balance impairments. Group yoga and group exercise sessions occur twice a week for 1 h for 8 weeks. Sessions are led by trained adaptive exercise specialists. Primary outcomes are balance and ANS function. Secondary outcomes are brain function and structure, cognition, quality of life, and qualitative experiences. Data analysis for primary and most secondary outcomes will be completed with mixed effect statistical methods to evaluate the within-subject factor of time (i.e., pre vs. post intervention), the between-subject factor of group (yoga vs. low-impact exercise), and interaction effects. Deductive and inductive techniques will be used to analyze qualitative data.

Discussion

Due to its accessibility and holistic nature, yoga has significant potential for improving balance and ANS function, along with other capacities, in adults with chronic ABI. Because there are also known benefits of exercise and group interaction, this study compares yoga to a similar, group exercise intervention to explore if yoga has a unique benefit for adults with chronic ABI.

Clinical trial registration:ClinicalTrials.gov, NCT05793827. Registered on March 31, 2023.
Assessment of mental workload across cognitive tasks using a passive brain-computer interface based on mean negative theta-band amplitudes
Authors: Gallegos Ayala Guillermo I. , Haslacher David , Krol Laurens R. , Soekadar Surjo R. , Zander Thorsten O.
Published: November 2023

Brain-computer interfaces (BCI) can provide real-time and continuous assessments of mental workload in different scenarios, which can subsequently be used to optimize human-computer interaction. However, assessment of mental workload is complicated by the task-dependent nature of the underlying neural signals. Thus, classifiers trained on data from one task do not generalize well to other tasks. Previous attempts at classifying mental workload across different cognitive tasks have therefore only been partially successful. Here we introduce a novel algorithm to extract frontal theta oscillations from electroencephalographic (EEG) recordings of brain activity and show that it can be used to detect mental workload across different cognitive tasks. We use a published data set that investigated subject dependent task transfer, based on Filter Bank Common Spatial Patterns. After testing, our approach enables a binary classification of mental workload with performances of 92.00 and 92.35%, respectively for either low or high workload vs. an initial no workload condition, with significantly better results than those of the previous approach. It, nevertheless, does not perform beyond chance level when comparing high vs. low workload conditions. Also, when an independent component analysis was done first with the data (and before any additional preprocessing procedure), even though we achieved more stable classification results above chance level across all tasks, it did not perform better than the previous approach. These mixed results illustrate that while the proposed algorithm cannot replace previous general-purpose classification methods, it may outperform state-of-the-art algorithms in specific (workload) comparisons.
Associations of 10 dietary habits with breast cancer: a Mendelian randomization study
Authors: Wang Xuyutian , Chen Lanlan , Cao Runxiang , Ma Ruolin , Liu Yutong , Zhao Qian , Du Ye
Published: November 2023

Introduction

Epidemiological studies have revealed a link between dietary habits and the breast cancer risk. The causality of the association between food consumption and breast cancer requires further investigation.

Methods

Using Mendelian randomization, we assessed the causal effects of 10 dietary habits on the risks of breast cancer and its subtypes (estrogen receptor [ER]  +  and ER- breast cancer). We obtained dietary pattern data in 2018 (number of single-nucleotide polymorphisms [SNPs]  =  9,851,867) and breast cancer data in 2017 (number of SNPs  =  10,680,257) from IEU OpenGWAS. Rigorous sensitivity analyses were conducted to ensure that the study results were credible and robust.

Results

We identified that genetic predisposition to higher dried fruit intake was linked to a reduced risk of overall breast cancer (inverse variance-weighted [IVW] odds ratio [OR] = 0.55; 95% confidence interval [CI]: 0.43–0.70; p = 1.75 × 10−6), ER+ breast cancer (IVW OR = 0.62; 95% CI: 0.47–0.82; p = 8.96 × 10−4) and ER− breast cancer (IVW OR = 0.48; 95% CI: 0.34–0.68; p = 3.18 × 10−5), whereas genetic predisposition to more oily fish intake was linked to a lower risk of ER+ breast cancer (IVW OR = 0.73; 95% CI: 0.53–0.99; p = 0.04).

Discussion

Our findings suggest that a genetic predisposition for dried fruit and oily fish consumption may be protective against breast cancer; however, further investigation is required.
Prevalence and prognostic significance of malnutrition in early-stage multiple system atrophy
Authors: Li Shirong , Zhang Lingyu , Hou Yanbing , Yang Tianmi , Li Chunyu , Wei Qianqian , Ou Ruwei , Chen Xueping , Shang Huifang
Published: November 2023

Background

Malnutrition is associated with poor survival in some diseases. However, the nutritional status in multiple system atrophy (MSA) is unknown, and the significance of malnutrition for the prediction of mortality in MSA has not been well established.

Objective

We aimed to determine the prevalence of malnutrition and the prognostic value of malnutrition in patients with early-stage MSA.

Methods

Patients diagnosed with early phase MSA (disease duration<3 years) were recruited, and they were followed every year until May 2023. The nutritional status of patients with MSA was assessed using the Controlling Nutritional Status (CONUT) score and Geriatric Nutritional Risk Index (GNRI). Kaplan–Meier survival analysis and Cox regression model were used to assess the prognostic value of malnutrition in MSA.

Results

A total of 224 patients with probable MSA (106 MSA died and 118 were still alive) and 213 matched healthy controls (HCs) were enrolled. According to COUNT score and GNRI, patients with MSA had higher prevalence of malnutrition than HCs (44.6% vs. 14.1 and 17.9% vs. 0.9%, respectively). The median survival from symptom onset in patients with MSA in the malnutrition group was shorter than those in the normal-nutrition group (5.98 vs. 7.06 years, p = 0.012) by COUNT score. Additionally, malnutrition increased the risk of mortality in patients with MSA (HR = 1.556, p = 0.030) and MSA-P (HR = 1.973, p = 0.042) by COUNT score.

Interpretation

Malnutrition was common in patients with early-stage MSA. Malnutrition increased the risk of mortality in patients with MSA, and early nutritional supplementation should be taken into consideration.
Association of skeletal muscle mass and risk of hypertension in Korean adults: secondary analysis of data from the community-based prospective cohort study
Authors: Bu So Young
Published: November 2023

Background

Cross-sectional studies have revealed a link between low muscle mass and hypertension. However, whether the degree of muscle mass predicts hypertension risk has not been confirmed. This study aimed to verify an association between skeletal muscle mass and incident hypertension in a longitudinal follow-up of middle-aged Korean adults.

Methods

The community-based prospective Korean Genome and Epidemiology Study (KoGES) data from 2,669 participants who were free of hypertension at baseline were prospectively assessed at 2-year intervals for 16 years. The participants were divided into tertiles T1–T3 of relative skeletal muscle mass (RSM) according to their baseline whole-body skeletal muscle mass measured as bioelectrical impedance. Incident hypertension was estimated using multivariate logistic regression with the Cox proportional hazard regression model.

Results

Over the 16-year follow-up, the rates of incident hypertension at RSM T1, T2, and T3 were 18.7, 17.1, and 13.4% in men (P for trend = 0.0002) and 18.8, 14.7, and 12.9% in women (P for trend = 0.0007), respectively. The multivariate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for the incidence of hypertension for men and women in T1 and T2 were 1.36 (1.11–1.67) and 1.59 (1.31–1.94), and 1.20 (0.99–1.46) and 1.70 (1.41–2.04), respectively, compared with T3 as the reference.

Conclusion

A low skeletal muscle mass in middle-aged Korean men and women was significantly associated with incident hypertension in later life. Further investigation is needed to comprehend the mechanisms of this relationship and validate the findings in a large cohort.