bluuebunny/crossref_metadata_2025 huggingface dataset:
Gut Microbiota and Psychiatric Disorders: A Two-Sample Mendelian Randomization Study
Authors: Ni Jing-Jing , Xu Qian , Yan Shan-Shan , Han Bai-Xue , Zhang Hong , Wei Xin-Tong , Feng Gui-Juan , Zhao Min , Pei Yu-Fang , Zhang Lei
Published: February 2022

Evidence supports the observational associations of gut microbiota with a variety of psychiatric disorders, but the causal nature of such associations remains obscure. Aiming to comprehensively investigate their causal relationship and to identify specific causal microbe taxa for psychiatric diseases, we conducted a two-sample Mendelian randomization (MR) analysis of gut microbiome with 15 psychiatric diseases. Specifically, the microbiome genome-wide association study (GWAS) in 18,473 individuals from the MiBioGen study was used as exposure sample, and the GWAS for 15 psychiatric diseases was used as outcome samples. One-hundred ninety bacterial taxa from six levels were available for analysis. At a multiple-testing corrected significance level (phylum P < 5.56 × 10–3, class P < 3.33 × 10–3, order P < 2.63 × 10–3, family P < 1.67 × 10–3, genus P < 4.90 × 10–4, and species P < 3.33 × 10–3), the following eight causal associations from seven bacterial features (one phylum + three classes + one order + one family + one species) were identified: family Prevotellaceae with autism spectrum disorder (P = 5.31 × 10–4), class Betaproteobacteria with bipolar disorder (P = 1.53 × 10–3), class Actinobacteria with schizophrenia (P = 1.33 × 10–3), class Bacteroidia and order Bacteroidales with Tourette syndrome (P = 2.51 × 10–3 and 2.51 × 10–3), phylum Actinobacteria and class Actinobacteria with extroversion (P = 8.22 × 10–4 and 1.09 × 10–3), and species Clostridium innocuum with neuroticism (P = 8.92 × 10–4). Sensitivity analysis showed no evidence of reverse causality, pleiotropy, and heterogeneity. Our findings offered novel insights into the gut microbiota–mediated development mechanism of psychiatric disorders.
Identification of Distinct Characteristics of Antibiofilm Peptides and Prospection of Diverse Sources for Efficacious Sequences
Authors: Bose Bipasa , Downey Taylor , Ramasubramanian Anand K. , Anastasiu David C.
Published: February 2022

A majority of microbial infections are associated with biofilms. Targeting biofilms is considered an effective strategy to limit microbial virulence while minimizing the development of antibiotic resistance. Toward this need, antibiofilm peptides are an attractive arsenal since they are bestowed with properties orthogonal to small molecule drugs. In this work, we developed machine learning models to identify the distinguishing characteristics of known antibiofilm peptides, and to mine peptide databases from diverse habitats to classify new peptides with potential antibiofilm activities. Additionally, we used the reported minimum inhibitory/eradication concentration (MBIC/MBEC) of the antibiofilm peptides to create a regression model on top of the classification model to predict the effectiveness of new antibiofilm peptides. We used a positive dataset containing 242 antibiofilm peptides, and a negative dataset which, unlike previous datasets, contains peptides that are likely to promote biofilm formation. Our model achieved a classification accuracy greater than 98% and harmonic mean of precision-recall (F1) and Matthews correlation coefficient (MCC) scores greater than 0.90; the regression model achieved an MCC score greater than 0.81. We utilized our classification-regression pipeline to evaluate 135,015 peptides from diverse sources for potential antibiofilm activity, and we identified 185 candidates that are likely to be effective against preformed biofilms at micromolar concentrations. Structural analysis of the top 37 hits revealed a larger distribution of helices and coils than sheets, and common functional motifs. Sequence alignment of these hits with known antibiofilm peptides revealed that, while some of the hits showed relatively high sequence similarity with known peptides, some others did not indicate the presence of antibiofilm activity in novel sources or sequences. Further, some of the hits had previously recognized therapeutic properties or host defense traits suggestive of drug repurposing applications. Taken together, this work demonstrates a new in silico approach to predicting antibiofilm efficacy, and identifies promising new candidates for biofilm eradication.
Molecular Data Reveal a Cryptic Diversity in the Genus Urotricha (Alveolata, Ciliophora, Prostomatida), a Key Player in Freshwater Lakes, With Remarks on Morphology, Food Preferences, and Distribution
Authors: Frantal Daniela , Agatha Sabine , Beisser Daniela , Boenigk Jens , Darienko Tatyana , Dirren-Pitsch Gianna , Filker Sabine , Gruber Michael , Kammerlander Barbara , Nachbaur Laura , Scheffel Ulrike , Stoeck Thorsten , Qian Kuimei , Weißenbacher Birgit , Pröschold Thomas , Sonntag Bettina
Published: February 2022

Species of the ciliate genus Urotricha are key players in freshwater plankton communities. In the pelagial of lakes, about 20 urotrich species occur throughout an annual cycle, some of which play a pivotal role in aquatic food webs. For example, during the phytoplankton spring bloom, they consume a remarkable proportion of the algal production. In ecological studies, urotrich ciliates are usually merely identified to genus rank and grouped into size classes. This is unsatisfying considering the distinct autecological properties of individual species and their specific spatial and temporal distribution patterns. As a basis for future research, we characterized in detail four common urotrich morphotypes, i.e., specimens identified as U. furcata and tentatively as U. agilis, U. pseudofurcata, and U. castalia, using state-of-the-art methods. We used an integrative polyphasic approach, in which morphological studies (in vivo observation, silver staining methods, scanning electron microscopy) were linked with a molecular approach exploiting four different gene fragments as taxonomic DNA barcodes with different resolution potential (SSU rDNA, ITS-1, ITS-2, hypervariable V4 and V9 regions of the SSU rDNA). We shed light on the diversity of urotrich ciliates as well as on their global distribution patterns, and annual cycles. Additionally, we coupled individual species occurrences and environmental parameters, and subsequently modeled the distribution and occurrence, using logistic regressions. Furthermore, for one strain putatively identified as U. castalia, we ascertained the optimal cultivation media and food preferences. Thereby, our comprehensive view on these important freshwater ciliates that frequently occur in environmental high throughput sequencing datasets worldwide will allow future studies to better exploit protistan plankton data from lakes.
Chlorine Tolerance and Cross-Resistance to Antibiotics in Poultry-Associated Salmonella Isolates in China
Authors: Xiao Xingning , Bai Li , Wang Sheng , Liu Lisha , Qu Xiaoyun , Zhang Jianmin , Xiao Yingping , Tang Biao , Li Yanbin , Yang Hua , Wang Wen
Published: February 2022

Chlorine disinfectants have been widely used in the poultry supply chain but this exposure can also result in the development of bacterial tolerance to chlorine and this is often linked to antibiotic cross-resistance. The objectives of this study were to investigate sodium hypochlorite (NaClO) tolerance of Salmonella isolated from poultry supply chains and evaluate cross-resistance. We collected 172 Salmonella isolates from poultry farms, slaughter houses and retail markets in China during 2019–2020. We found that S. Enteritidis, S. Kentucky, and S. Typhimurium constituted > 80% of our Salmonella isolates. Overall, 68% of Salmonella isolates were resistant to > 3 antibiotics and S. Kentucky displayed a significantly (p > 0.05) higher frequency (93.2%) of multidrug resistance than the other serovars. Tolerance to chlorine at MIC > 256 mg/L was detected in 93.6% of isolates (161/172) and tolerant isolates displayed higher decimal reduction times (D value) and less ultrastructural damage than did the suspectable strains under chlorine stress. Spearman analysis indicated significant positive correlations between chlorine tolerance (evaluated by the OD method) and antibiotic resistance (p < 0.05) to ceftiofur, tetracycline, ciprofloxacin and florfenicol and this was most likely due to efflux pump over-expression. The most frequently detected chlorine resistance gene was qacEΔ1 (83.1%, n = 143) and we found a positive correlation between its presence and MIC levels (r = 0.66, p < 0.0001). Besides, we found weak correlations between chlorine-tolerance and antibiotic resistance genes. Our study indicated that chlorine disinfectants most likely played an important role in the emergence of chlorine tolerance and spread of antibiotic resistance and therefore does not completely control the risk of food-borne disease. The issue of disinfectant resistance should be examined in more detail at the level of the poultry production chain.
Impacts of Continuous Cropping on Fungal Communities in the Rhizosphere Soil of Tibetan Barley
Authors: Yao Youhua , Zhao Yuan , Yao Xiaohua , Bai Yixiong , An Likun , Li Xin , Wu Kunlun
Published: February 2022

Microbial community structures and keystone species play critical roles in soil ecological processes; however, their responses to the continuous cropping of plants are virtually unknown. Here, we investigated the community dynamics and keystone species of fungal communities in the rhizosphere soils of continuously cropped Tibetan barley (a principal cereal cultivated on the Qinghai–Tibetan Plateau). We found that the Chao1 and Phylogenetic Diversity (PD) indices decreased with increased cropping years. The relative abundance of the genera Cystofilobasidium, Mucor, and Ustilago increased with the extension of continuous cropping years, whereas Fusarium showed the opposite pattern. Furthermore, long-term monocropped Tibetan barley simplified the complexity of the co-occurrence networks. Keystone operational taxonomic units (OTUs) changed with continuous cropping, and most of the keystone OTUs belonged to the phylum Ascomycota, suggesting their important roles in rhizosphere soil. Overall, this study revealed that the continuous cropping of Tibetan barley impacted both on the richness, phylogenetic diversity, and co-occurrence network of fungal community in the rhizosphere. These findings enhance our understanding of how rhizosphere fungal communities respond to monocropped Tibetan barley.
Classification of Hepatocellular Carcinoma Based on N6-Methylandenosine–Related lncRNAs Profiling
Authors: Yin Lu , Zhou Liuzhi , Gao Shiqi , Feng Yina , Zhu Hanzhang , Xiang Jingjing , Xu Rujun
Published: February 2022

HCC is one of the most common types of malignancies worldwide and the fourth-leading cause of cancer deaths. Thus, there is an urgent need to search for novel targeted therapies in HCC. 186 m6a-related lncRNAs were screened for subsequent analysis. Two distinct m6A modification clusters were identified to be associated with the overall prognosis in TCGA-LIHC based on the m6A-related lncRNAs profiling, followed by univariate Cox regression analysis. In addition, four m6A-related lncRNAs prognostic signatures were developed and validated that could predict the OS of HCC patients, followed by univariate Cox regression, LASSO regression, and multivariate Cox regression analysis. Moreover, four m6A-related lncRNAs were identified to be related to HCC prognosis. ESTIMATE was used to evaluate the stromal score, immune score, ESTIMATE score, and tumor purity of each HCC sample. ssGSEA was performed to identify the enrichment levels of 29 immune signatures in each sample. Finally, quantitative real-time polymerase chain reaction shown that KDM4A-AS1, BACE1-AS, and NRAV expressions were upregulated in HCC patients. We proved that our m6A-related lncRNAs signature had powerful and robust ability for predicting OS of different HCC subgroups.
Sampling of Protein Conformational Space Using Hybrid Simulations: A Critical Assessment of Recent Methods
Authors: Kaynak Burak T. , Krieger James M. , Dudas Balint , Dahmani Zakaria L. , Costa Mauricio G. S. , Balog Erika , Scott Ana Ligia , Doruker Pemra , Perahia David , Bahar Ivet
Published: February 2022

Recent years have seen several hybrid simulation methods for exploring the conformational space of proteins and their complexes or assemblies. These methods often combine fast analytical approaches with computationally expensive full atomic molecular dynamics (MD) simulations with the goal of rapidly sampling large and cooperative conformational changes at full atomic resolution. We present here a systematic comparison of the utility and limits of four such hybrid methods that have been introduced in recent years: MD with excited normal modes (MDeNM), collective modes-driven MD (CoMD), and elastic network model (ENM)-based generation, clustering, and relaxation of conformations (ClustENM) as well as its updated version integrated with MD simulations (ClustENMD). We analyzed the predicted conformational spaces using each of these four hybrid methods, applied to four well-studied proteins, triosephosphate isomerase (TIM), 3-phosphoglycerate kinase (PGK), HIV-1 protease (PR) and HIV-1 reverse transcriptase (RT), which provide extensive ensembles of experimental structures for benchmarking and comparing the methods. We show that a rigorous multi-faceted comparison and multiple metrics are necessary to properly assess the differences between conformational ensembles and provide an optimal protocol for achieving good agreement with experimental data. While all four hybrid methods perform well in general, being especially useful as computationally efficient methods that retain atomic resolution, the systematic analysis of the same systems by these four hybrid methods highlights the strengths and limitations of the methods and provides guidance for parameters and protocols to be adopted in future studies.
Melatonin Treatment for Sleep Disorders in Parkinson's Disease: A Meta-Analysis and Systematic Review
Authors: Ma Hongxia , Yan Junqiang , Sun Wenjie , Jiang Menghan , Zhang Yongjiang
Published: February 2022

Objective

The efficacy of melatonin on sleep disorders in Parkinson's disease (PD) is still unclear. The purpose of this study was to investigate the efficacy of melatonin on sleep disorders in PD by summarizing evidence from randomized clinical trials (RCTs).

Methods

PubMed, Cochrane Library, EMBASE, and Web of Science databases were searched for studies published before 20 August 2021. Results were analyzed using Review Manager 5.2 software. We used Trial Sequential Analysis (TSA) software to avoid false-positive results caused by random errors.

Results

We included 7 studies in this systematic review and meta-analysis. The results of the meta-analysis showed that compared with placebo, the subjective sleep quality of patients with PD significantly improved after melatonin treatment (MD = −2.19, 95% CI: −3.53 to −0.86, P = 0.001). In the systematic review, we qualitatively analyzed the efficacy of melatonin on the objective sleep quality of patients with PD, and the results showed that melatonin exerted a positive effect with good safety and tolerability. However, there was no significant improvement in excessive daytime sleepiness assessed by the Epworth Sleepiness Scale (ESS).

Conclusion

We found that melatonin can significantly improve the subjective and objective sleep quality of patients with PD with good safety and tolerability. Melatonin could be considered an effective treatment for insomnia in patients with PD.
Alteration of Neural Network Activity With Aging Focusing on Temporal Complexity and Functional Connectivity Within Electroencephalography
Authors: Ando Momo , Nobukawa Sou , Kikuchi Mitsuru , Takahashi Tetsuya
Published: February 2022

With the aging process, brain functions, such as attention, memory, and cognitive functions, degrade over time. In a super-aging society, the alteration of neural activity owing to aging is considered crucial for interventions for the prevention of brain dysfunction. The complexity of temporal neural fluctuations with temporal scale dependency plays an important role in optimal brain information processing, such as perception and thinking. Complexity analysis is a useful approach for detecting cortical alteration in healthy individuals, as well as in pathological conditions, such as senile psychiatric disorders, resulting in changes in neural activity interactions among a wide range of brain regions. Multi-fractal (MF) and multi-scale entropy (MSE) analyses are known methods for capturing the complexity of temporal scale dependency of neural activity in the brain. MF and MSE analyses exhibit high accuracy in detecting changes in neural activity and are superior with regard to complexity detection when compared with other methods. In addition to complex temporal fluctuations, functional connectivity reflects the integration of information of brain processes in each region, described as mutual interactions of neural activity among brain regions. Thus, we hypothesized that the complementary relationship between functional connectivity and complexity could improve the ability to detect the alteration of spatiotemporal patterns observed on electroencephalography (EEG) with respect to aging. To prove this hypothesis, this study investigated the relationship between the complexity of neural activity and functional connectivity in aging based on EEG findings. Concretely, MF and MSE analyses were performed to evaluate the temporal complexity profiles, and phase lag index analyses assessing the unique profile of functional connectivity were performed based on the EEGs conducted for young and older participants. Subsequently, these profiles were combined through machine learning. We found that the complementary relationship between complexity and functional connectivity improves the classification accuracy among aging participants. Thus, the outcome of this study could be beneficial in formulating interventions for the prevention of age-related brain dysfunction.
Toward a Feasible Solution for Removing Toxic Mercury and Chromium From Water Using Copper Oxide Nanoparticles
Authors: Raul Prasanta K. , Das Bodhaditya , Umlong Iohborlang M. , Devi Rashmi Rekha , Tiwari Gaurav , Kamboj Dev Vrat
Published: February 2022

Objective: Water contaminated with heavy metals causes serious environmental issues for people. Mercury and chromium are considered to be extremely toxic for public health. Diversified technologies have been introduced to purify contaminated water; however, only a few become successful in reducing mercury and chromium below the permissible limit of drinking water (0.001 and 0.05 ppm, respectively, WHO/BIS Guidelines). Our main aim was to synthesize suitable nanoscale materials to make water potable by removing mercury and chromium from contaminated water while keeping essential elements as per the WHO/BIS guidelines.

Methods: Copper(II) oxide nanomaterials are synthesized following a wet chemical process as per earlier reported procedures. Nanoparticles with average diameter of 10–20 nm are formed. XRD confirms the formation of orthorhombic CuO nanoparticles.

Results: The nanoparticles are efficient in removing mercury from 200 ppb to less than 50 ppb (75%) and chromium from 200 ppb to less than 16 ppb (92%) over a wide range of pH.

Conclusion: The nanomaterials have great potential in removing toxic heavy metals from contaminated water. The materials can be applied to integrated water purification systems to produce potable water.
Contributions of h- and Na+/K+ Pump Currents to the Generation of Episodic and Continuous Rhythmic Activities
Authors: Sharples Simon A. , Parker Jessica , Vargas Alex , Milla-Cruz Jonathan J. , Lognon Adam P. , Cheng Ning , Young Leanne , Shonak Anchita , Cymbalyuk Gennady S. , Whelan Patrick J.
Published: February 2022

Developing spinal motor networks produce a diverse array of outputs, including episodic and continuous patterns of rhythmic activity. Variation in excitability state and neuromodulatory tone can facilitate transitions between episodic and continuous rhythms; however, the intrinsic mechanisms that govern these rhythms and their transitions are poorly understood. Here, we tested the capacity of a single central pattern generator (CPG) circuit with tunable properties to generate multiple outputs. To address this, we deployed a computational model composed of an inhibitory half-center oscillator (HCO). Following predictions of our computational model, we tested the contributions of key properties to the generation of an episodic rhythm produced by isolated spinal cords of the newborn mouse. The model recapitulates the diverse state-dependent rhythms evoked by dopamine. In the model, episodic bursting depended predominantly on the endogenous oscillatory properties of neurons, with Na+/K+ ATPase pump (IPump) and hyperpolarization-activated currents (Ih) playing key roles. Modulation of either IPump or Ih produced transitions between episodic and continuous rhythms and silence. As maximal activity of IPump decreased, the interepisode interval and period increased along with a reduction in episode duration. Decreasing maximal conductance of Ih decreased episode duration and increased interepisode interval. Pharmacological manipulations of Ih with ivabradine, and IPump with ouabain or monensin in isolated spinal cords produced findings consistent with the model. Our modeling and experimental results highlight key roles of Ih and IPump in producing episodic rhythms and provide insight into mechanisms that permit a single CPG to produce multiple patterns of rhythmicity.
Müller Glia in Retinal Development: From Specification to Circuit Integration
Authors: Tworig Joshua M. , Feller Marla B.
Published: February 2022

Müller glia of the retina share many features with astroglia located throughout the brain including maintenance of homeostasis, modulation of neurotransmitter spillover, and robust response to injury. Here we present the molecular factors and signaling events that govern Müller glial specification, patterning, and differentiation. Next, we discuss the various roles of Müller glia in retinal development, which include maintaining retinal organization and integrity as well as promoting neuronal survival, synaptogenesis, and phagocytosis of debris. Finally, we review the mechanisms by which Müller glia integrate into retinal circuits and actively participate in neuronal signaling during development.
Reinforcement Learning Model With Dynamic State Space Tested on Target Search Tasks for Monkeys: Self-Determination of Previous States Based on Experience Saturation and Decision Uniqueness
Authors: Katakura Tokio , Yoshida Mikihiro , Hisano Haruki , Mushiake Hajime , Sakamoto Kazuhiro
Published: February 2022

The real world is essentially an indefinite environment in which the probability space, i. e., what can happen, cannot be specified in advance. Conventional reinforcement learning models that learn under uncertain conditions are given the state space as prior knowledge. Here, we developed a reinforcement learning model with a dynamic state space and tested it on a two-target search task previously used for monkeys. In the task, two out of four neighboring spots were alternately correct, and the valid pair was switched after consecutive correct trials in the exploitation phase. The agent was required to find a new pair during the exploration phase, but it could not obtain the maximum reward by referring only to the single previous one trial; it needed to select an action based on the two previous trials. To adapt to this task structure without prior knowledge, the model expanded its state space so that it referred to more than one trial as the previous state, based on two explicit criteria for appropriateness of state expansion: experience saturation and decision uniqueness of action selection. The model not only performed comparably to the ideal model given prior knowledge of the task structure, but also performed well on a task that was not envisioned when the models were developed. Moreover, it learned how to search rationally without falling into the exploration–exploitation trade-off. For constructing a learning model that can adapt to an indefinite environment, the method of expanding the state space based on experience saturation and decision uniqueness of action selection used by our model is promising.
Chiropractic Spinal Adjustment Increases the Cortical Drive to the Lower Limb Muscle in Chronic Stroke Patients
Authors: Navid Muhammad Samran , Niazi Imran Khan , Lelic Dina , Amjad Imran , Kumari Nitika , Shafique Muhammad , Holt Kelly , Rashid Usman , Drewes Asbjørn Mohr , Haavik Heidi
Published: February 2022

This study aimed to investigate the effects of a single session of chiropractic spinal adjustment on the cortical drive to the lower limb in chronic stroke patients. In a single-blinded, randomized controlled parallel design study, 29 individuals with chronic stroke and motor weakness in a lower limb were randomly divided to receive either chiropractic spinal adjustment or a passive movement control intervention. Before and immediately after the intervention, transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEPs) were recorded from the tibialis anterior (TA) muscle of the lower limb with the greatest degree of motor weakness. Differences in the averaged peak-peak MEP amplitude following interventions were calculated using a linear regression model. Chiropractic spinal adjustment elicited significantly larger MEP amplitude (pre = 0.24 ± 0.17 mV, post = 0.39 ± 0.23 mV, absolute difference = +0.15 mV, relative difference = +92%, p < 0.001) compared to the control intervention (pre = 0.15 ± 0.09 mV, post = 0.16 ± 0.09 mV). The results indicate that chiropractic spinal adjustment increases the corticomotor excitability of ankle dorsiflexor muscles in people with chronic stroke. Further research is required to investigate whether chiropractic spinal adjustment increases dorsiflexor muscle strength and walking function in people with stroke.
A2DS2 Score Combined With Clinical and Neuroimaging Factors Better Predicts Stroke-Associated Pneumonia in Hyperacute Cerebral Infarction
Authors: Yu Yaoyao , Xia Tianyi , Tan Zhouli , Xia Huwei , He Shenping , Sun Han , Wang Xifan , Song Haolan , Chen Weijian
Published: February 2022

Objective

To investigate the predictors of stroke-associated pneumonia (SAP) and poor functional outcome in patients with hyperacute cerebral infarction (HCI) by combining clinical factors, laboratory tests and neuroimaging features.

Methods

We included 205 patients with HCI from November 2018 to December 2019. The diagnostic criterion for SAP was occurrence within 7 days of the onset of stroke. Poor outcome was defined as a functional outcome based on a 3-months MRS score >3. The relationship of demographic, laboratory and neuroimaging variables with SAP and poor outcome was investigated using univariate and multivariate analyses.

Results

Fifty seven (27.8%) patients were diagnosed with SAP and 40 (19.5%) developed poor outcomes. A2DS2 score (OR = 1.284; 95% CI: 1.048–1.574; P = 0.016), previous stroke (OR = 2.630; 95% CI: 1.122–6.163; P = 0.026), consciousness (OR = 2.945; 95% CI: 1.514–5.729; P < 0.001), brain atrophy (OR = 1.427; 95% CI: 1.040–1.959; P = 0.028), and core infarct volume (OR = 1.715; 95% CI: 1.163–2.528; P = 0.006) were independently associated with the occurrence of SAP. Therefore, we combined these variables into a new SAP prediction model with the C-statistic of 0.84 (95% CI: 0.78–0.90). Fasting plasma glucose (OR = 1.404; 95% CI: 1.202–1.640; P < 0.001), NIHSS score (OR = 1.088; 95% CI: 1.010–1.172; P = 0.026), previous stroke (OR = 4.333; 95% CI: 1.645–11.418; P = 0.003), SAP (OR = 3.420; 95% CI: 1.332–8.787; P = 0.011), basal ganglia-dilated perivascular spaces (BG-dPVS) (OR = 2.124; 95% CI: 1.313–3.436; P = 0.002), and core infarct volume (OR = 1.680; 95% CI: 1.166–2.420; P = 0.005) were independently associated with poor outcome. The C-statistic of the outcome model was 0.87 (95% CI: 0.81–0.94). Furthermore, the SAP model significantly improved discrimination and net benefit more than the A2DS2 scale, with a C-statistic of 0.76 (95% CI: 0.69–0.83).

Conclusions

After the addition of neuroimaging features, the models exhibit good differentiation and calibration for the prediction of the occurrence of SAP and the development of poor outcomes in HCI patients. The SAP model could better predict the SAP, representing a helpful and valid tool to obtain a net benefit compared with the A2DS2 scale.
Networking of the Human Cerebellum: From Anatomo-Functional Development to Neurosurgical Implications
Authors: De Benedictis Alessandro , Rossi-Espagnet Maria Camilla , de Palma Luca , Carai Andrea , Marras Carlo Efisio
Published: February 2022

In the past, the cerebellum was considered to be substantially involved in sensory-motor coordination. However, a growing number of neuroanatomical, neuroimaging, clinical and lesion studies have now provided converging evidence on the implication of the cerebellum in a variety of cognitive, affective, social, and behavioral processes as well. These findings suggest a complex anatomo-functional organization of the cerebellum, involving a dense network of cortical territories and reciprocal connections with many supra-tentorial association areas. The final architecture of cerebellar networks results from a complex, highly protracted, and continuous development from childhood to adulthood, leading to integration between short-distance connections and long-range extra-cerebellar circuits. In this review, we summarize the current evidence on the anatomo-functional organization of the cerebellar connectome. We will focus on the maturation process of afferent and efferent neuronal circuitry, and the involvement of these networks in different aspects of neurocognitive processing. The final section will be devoted to identifying possible implications of this knowledge in neurosurgical practice, especially in the case of posterior fossa tumor resection, and to discuss reliable strategies to improve the quality of approaches while reducing postsurgical morbidity.
Preliminary Outcomes of Combined Treadmill and Overground High-Intensity Interval Training in Ambulatory Chronic Stroke
Authors: Boyne Pierce , Doren Sarah , Scholl Victoria , Staggs Emily , Whitesel Dustyn , Carl Daniel , Shatz Rhonna , Sawyer Russell , Awosika Oluwole O. , Reisman Darcy S. , Billinger Sandra A. , Kissela Brett , Vannest Jennifer , Dunning Kari
Published: February 2022

Purpose

Locomotor high-intensity interval training (HIIT) is a promising intervention for stroke rehabilitation. However, overground translation of treadmill speed gains has been somewhat limited, some important outcomes have not been tested and baseline response predictors are poorly understood. This pilot study aimed to guide future research by assessing preliminary outcomes of combined overground and treadmill HIIT.

Materials and Methods

Ten participants >6 months post-stroke were assessed before and after a 4-week no-intervention control phase and a 4-week treatment phase involving 12 sessions of overground and treadmill HIIT.

Results

Overground and treadmill gait function both improved during the treatment phase relative to the control phase, with overground speed changes averaging 61% of treadmill speed changes (95% CI: 33–89%). Moderate or larger effect sizes were observed for measures of gait performance, balance, fitness, cognition, fatigue, perceived change and brain volume. Participants with baseline comfortable gait speed <0.4 m/s had less absolute improvement in walking capacity but similar proportional and perceived changes.

Conclusions

These findings reinforce the potential of locomotor HIIT research for stroke rehabilitation and provide guidance for more definitive studies. Based on the current results, future locomotor HIIT studies should consider including: (1) both overground and treadmill training; (2) measures of cognition, fatigue and brain volume, to complement typical motor and fitness assessment; and (3) baseline gait speed as a covariate.
Clinical Predictors of Relapse in a Cohort of Steroid-Treated Patients With Well-Controlled Myasthenia Gravis
Authors: Su Shengyao , Lei Lin , Fan Zhirong , Zhang Shu , Wen Qi , Wang Jingsi , Lu Yan , Di Li , Wang Min , Chen Hai , Da Yuwei
Published: February 2022

Objective

Despite the high efficiency of glucocorticoids (GCs), ~18–34% patients with myasthenia gravis (MG) may experience relapses of the disease. Here, we aim to identify clinical factors related to relapses during steroid tapering or after withdrawal in MG patients who were well-managed on steroid monotherapy.

Methods

We conducted a retrospective study on 125 MG patients from the Xuanwu Hospital MG Trial Database. Patients were treated with corticosteroids and achieved minimal manifestation status (MMS) or better. Patients were divided into steroid reduction subset (N = 74) and steroid withdrawal subset (N = 51). Clinical characteristics and therapeutic data were compared between patients with disease relapse and those who maintained clinical remission at the last follow-ups. Cox proportional hazards regression models were used to identify risk factors of relapse in each subset.

Results

Thirty-seven (29.6%) patients experienced relapses during the follow-up periods. Relapse during the steroid reduction was significantly associated with drug reducing duration (HR = 0.81, 95%CI 0.74–0.89, P < 0.001). Risk of relapse was augmented if the drug reducing duration was <11.5 months (HR 27.80, 95%CI 5.88–131.57, P < 0.001). Among patients who discontinued the steroids, those with onset symptoms of bulbar weakness (adjusted HR 3.59, 95%CI 1.19–10.81, P = 0.023) were more likely to experience relapse.

Conclusion

Our study demonstrated that patients could benefit from prolonged steroid-reducing duration to prevent disease relapse. Patients with bulbar weakness at disease onset should be proposed to take long-term steroids or other immunosuppressants.
Dual Antiplatelet Therapy in Patients With Minor Stroke Receiving Intravenous Thrombolysis
Authors: Xu Zhaohan , Chen Nihong , Sun Huiling , Jiang Teng , Deng Qiwen , Zhou Junshan , Zhang Yingdong
Published: February 2022

Introduction

Concern over the potential severe bleeding risk of dual antiplatelet therapy for patients with minor stroke after intravenous thrombolysis (IVT) leads to different antiplatelet strategies in the secondary prevention of stroke. Our aim was to investigate the effect of dual antiplatelet therapy on patients with minor ischemic stroke receiving IVT.

Methods

From November 2016 to April 2021, a total of 855 consecutive patients who received IVT were observed. We collected and analyzed demographic characteristics, medical history, clinical information, and important time metrics of patients with minor ischemic stroke. Comparative and multivariate logistic regression analyses were used to explore the clinical significance of single or dual antiplatelet therapy after IVT. Propensity score matching analyses (1:1 matching including baseline characteristics of patients) were also performed.

Results

A total of 245 patients were enrolled in the study (118 patients in the single antiplatelet therapy group and 127 patients in the dual antiplatelet group). No significant difference was found in baseline characteristics except stroke etiology (p < 0.001) for patients with minor stroke. The dual antiplatelet group showed a higher proportion of 90-day modified Rankin Scale (mRS) (0–1) than the single antiplatelet group (p = 0.030). Furthermore, patients receiving dual antiplatelet therapy had excellent outcomes (90-day mRS 0–1) after adjustment (odds ratio [OR] 2.76, 95% CI 1.27–6.01, p = 0.010). Other secondary outcomes (recurrent stroke within 90 days, symptomatic intracerebral hemorrhage, and early neurological deterioration) were not significantly different between the two groups. These findings were generally consistent in propensity score analyses.

Conclusions

Dual antiplatelet therapy may be a potential therapeutic approach in patients with minor stroke receiving IVT. Further randomized controlled trials are required to confirm this finding.
Synergistic Immediate Cortical Activation on Mirror Visual Feedback Combined With a Soft Robotic Bilateral Hand Rehabilitation System: A Functional Near Infrared Spectroscopy Study
Authors: Qiu Yaxian , Zheng Yuxin , Liu Yawen , Luo Wenxi , Du Rongwei , Liang Junjie , Yilifate Anniwaer , You Yaoyao , Jiang Yongchun , Zhang Jiahui , Chen Aijia , Zhang Yanni , Huang Siqi , Wang Benguo , Ou Haining , Lin Qiang
Published: February 2022

Background

Mirror visual feedback (MVF) has been widely used in neurological rehabilitation. Due to the potential gain effect of the MVF combination therapy, the related mechanisms still need be further analyzed.

Methods

Our self-controlled study recruited 20 healthy subjects (age 22.150 ± 2.661 years) were asked to perform four different visual feedback tasks with simultaneous functional near infrared spectroscopy (fNIRS) monitoring. The right hand of the subjects was set as the active hand (performing active movement), and the left hand was set as the observation hand (static or performing passive movement under soft robotic bilateral hand rehabilitation system). The four VF tasks were designed as RVF Task (real visual feedback task), MVF task (mirror visual feedback task), BRM task (bilateral robotic movement task), and MVF + BRM task (Mirror visual feedback combined with bilateral robotic movement task).

Results

The beta value of the right pre-motor cortex (PMC) of MVF task was significantly higher than the RVF task (RVF task: -0.015 ± 0.029, MVF task: 0.011 ± 0.033, P = 0.033). The beta value right primary sensorimotor cortex (SM1) in MVF + BRM task was significantly higher than MVF task (MVF task: 0.006 ± 0.040, MVF + BRM task: 0.037 ± 0.036, P = 0.016).

Conclusion

Our study used the synchronous fNIRS to compare the immediate hemodynamics cortical activation of four visual feedback tasks in healthy subjects. The results showed the synergistic gain effect on cortical activation from MVF combined with a soft robotic bilateral hand rehabilitation system for the first time, which could be used to guide the clinical application and the future studies.
Why Has the Ability to Regenerate Following CNS Injury Been Repeatedly Lost Over the Course of Evolution?
Authors: Blackshaw Seth
Published: February 2022

While many vertebrates can regenerate both damaged neurons and severed axons in the central nervous system (CNS) following injury, others, including all birds and mammals, have lost this ability for reasons that are still unclear. The repeated evolutionary loss of regenerative competence seems counterintuitive, and any explanation must account for the fact that regenerative competence is lost in both cold-blooded and all warm-blooded clades, that both injury-induced neurogenesis and axonal regeneration tend to be lost in tandem, and that mammals have evolved dedicated gene regulatory networks to inhibit injury-induced glia-to-neuron reprogramming. Here, different hypotheses that have been proposed to account for evolutionary loss of regenerative competence are discussed in the light of new insights obtained into molecular mechanisms that control regeneration in the central nervous system. These include pleiotropic effects of continuous growth, enhanced thyroid hormone signaling, prevention of neoplasia, and improved memory consolidation. Recent evidence suggests that the most compelling hypothesis, however, may be selection for greater resistance to the spread of intra-CNS infections, which has led to both enhanced reactive gliosis and a loss of injury-induced neurogenesis and axonal regeneration. Means of testing these hypotheses, and additional data that are urgently needed to better understand the evolutionary pressures and mechanisms driving loss of regenerative competence, are also discussed.
Heat-Killed Lacticaseibacillus paracasei GMNL-653 Exerts Antiosteoporotic Effects by Restoring the Gut Microbiota Dysbiosis in Ovariectomized Mice
Authors: Jhong Jhih-Hua , Tsai Wan-Hua , Yang Li-Chan , Chou Chia-Hsuan , Lee Tzong-Yi , Yeh Yao-Tsung , Huang Cheng-Hsieh , Luo Yueh-Hsia
Published: February 2022

Osteoporosis is a metabolic inflammatory disease, an imbalance occurs between bone resorption and formation, leading to bone loss. Anti-inflammatory diet is considered having the potential to ameliorate osteoporosis. Heat-killed probiotics exhibit health benefits in relation to their immunomodulatory effects, but the detail mechanism involved in gut microbiota balance, host metabolism, immunity, and bone homeostasis remains unclear. In this study, we evaluated the antiosteoporotic effects of heat-killed Lacticaseibacillus paracasei GMNL-653 in vitro and in ovariectomized (OVX) mice. Furthermore, whole-genome sequencing and comparative genomics analysis demonstrated potentially genes involved in antiosteoporotic activity. The GMNL-653 exerts anti-inflammatory activity which restored gut microbiota dysbiosis and maintained intestinal barrier integrity in the OVX mice. The levels of IL-17 and LPS in the sera decreased following GMNL-653 treatment compared with those of the vehicle control; mRNA levels of RANKL were reduced and TGF-β and IL-10 enhanced in OVX-tibia tissue after treatment. The levels of IL-17 were significantly associated with gut microbiota dysbiosis. Gut microbial metagenomes were further analyzed by PICRUSt functional prediction, which reveal that GMNL-653 intervention influence in several host metabolic pathways. The analysis of whole-genome sequencing accompanied by comparative genomics on three L. paracasei strains revealed a set of GMNL-653 genes that are potentially involved in antiosteoporotic activity. Our findings validated antiosteoporotic activity of heat-killed GMNL-653 using in vitro and in vivo models, to whole-genome sequencing and identifying genes potentially involved in this gut microbiota–bone axis.
Practical Considerations for the Daratumumab Management in Portuguese Routine Clinical Practice: Recommendations From an Expert Panel of Hematologists
Authors: Geraldes Catarina , Neves Manuel , Chacim Sérgio , da Costa Fernando Leal
Published: February 2022

The recent therapeutic progress in multiple myeloma (MM) has led to the introduction of novel and highly potent drug classes. Daratumumab was the first CD38-targeting antibody showing to be effective and safe in MM patients as monotherapy and in combination regimens, which led to its rapid implementation in clinical practice. Considering that treatment discontinuation for drug-related adverse events can impact patients’ quality of life and outcomes, the treatment decision should consider different factors and be weighted for each patient individually. Here, we aimed to guide clinicians using daratumumab treatment for MM by addressing practical real-world considerations based on an expert panel of Portuguese hematologists. Carefully following the recommendations mentioned in daratumumab’s SmPC, and of those from other drugs used in combination regimens, along with ensuring a good communication with all healthcare professionals involved, is critical to prevent any complications arising from treatment. The risk of infection should be assessed for all patients under treatment with daratumumab and patients should be educated on the potential adverse events. Recommendations on prophylaxis and vaccination should be considered to avoid infections, and delays in the planned therapeutic schedule may be required to prevent adverse consequences of hematological toxicity. Daratumumab treatment is effective and feasible in patients with renal impairment, although careful patient monitoring and a frequent communication with the Nephrology department are of the utmost importance. Sharing clinical practice plays an important role in medical education by allowing to maximize treatment efficacy and minimize its safety risks.
Unexpected Change of Surgical Plans and Contingency Strategies in Computer-Assisted Free Flap Jaw Reconstruction: Lessons Learned From 98 Consecutive Cases
Authors: Pu Jane J. , Choi Wing Shan , Yang Wei-fa , Zhu Wang-yong , Su Yu-xiong
Published: February 2022

Background

Computer-assisted surgeries (CAS) are increasingly being adopted as the treatment of choice for jaw reconstructions with osseous free flaps. Although unexpected change of surgical plans remains a major concern of CAS, there are few studies focusing on this unfavorable clinical scenario. The aim of the present study was to investigate the rate of unexpected change of surgical plans and potential influential parameters, and to discuss the contingency strategies.

Methods

A retrospective study was performed to evaluate all the patients who underwent computer-assisted jaw resections and osseous free flap reconstructions. The postoperative radiographs were reviewed and compared with the preoperative surgical plans. Operating records were examined to analyze the reasons for unexpected change of surgical plans and the management. The potential influential parameters for the change of surgical plans were analyzed using Fisher-exact test. The difference was regarded as statistically significant for a p-value less than 5%.

Results

From Nov 2014 to Oct 2021, a total of 98 consecutive computer-assisted free flap jaw reconstruction cases with osseous free flaps were included in this study. Our experience showed that 5.1% of the patients (five cases) needed intra-operative change of the surgical plans. We summarized the unexpected change of surgical plans and the contingency strategies as four clinical scenarios, including extended resection and reconstruction, shortened resection and reconstruction, modified resection without changing reconstruction, and modified reconstruction without changed resection. None of the potential influential parameters was identified as significant in relation to unexpected change of surgical plans intraoperatively.

Conclusion

Our experience shows that with the comprehensive methodology for computer-assisted free flap jaw reconstruction surgery planning, we can minimize the possibility of unexpected change of surgical plans during surgery. The lessons learned from our 98 consecutive cases can help beginners prevent unexpected change of surgical plans and rationalize contingency strategies in computer-assisted free flap jaw reconstruction.
Prognostic Significance of the Systemic Immune-Inflammation Index (SII) in Patients With Small Cell Lung Cancer: A Meta-Analysis
Authors: Zhou Yuting , Dai Menglu , Zhang Zongxin
Published: February 2022

Background

Previous studies have investigated the prognostic value of the systemic immune-inflammation index (SII) in small cell lung cancer (SCLC). However, the results have been inconsistent. The study aimed to investigate the prognostic and clinicopathological significance of SII in SCLC through a meta-analysis.

Methods

The PubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure databases were thoroughly searched. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to evaluate the prognostic value of the SII for survival outcomes. The combined odds ratios (ORs) and 95% CIs were used to evaluate the correlation between SII and clinicopathological features.

Results

Eight studies comprising 2,267 patients were included in the meta-analysis. Pooled analyses indicated that a high SII was significantly associated with worse overall survival (OS) (HR=1.52, 95% CI=1.15–2.00, p=0.003) but not progression-free survival (HR=1.38, 95% CI=0.81–2.35, p=0.238) in patients with SCLC. Moreover, a high SII was associated with extensive-stage SCLC (OR=2.43, 95% CI=1.86–3.17, p<0.001). However, there was a non-significant correlation between SII and age, sex, smoking history, Karnofsky Performance Status score, or initial therapeutic response.

Conclusion

Our meta-analysis demonstrated that a high SII could be an efficient prognostic indicator of OS in SCLC. We recommend adopting SII to predict OS in patients with SCLC, and SII in combination with other parameters or biomarkers may aid in addressing the clinical strategy and choosing the best treatment for an individual patient.