bluuebunny/crossref_metadata_2025 huggingface dataset:
Association Between a History of Nontyphoidal Salmonella and the Risk of Systemic Lupus Erythematosus: A Population-Based, Case-Control Study
Authors: Tu Ting-Yu , Yeh Chiu-Yu , Hung Yao-Min , Chang Renin , Chen Hsin-Hua , Wei James Cheng-Chung
Published: November 2021

Objective

We investigated the correlation between nontyphoidal Salmonella (NTS) infection and systemic lupus erythematosus (SLE) risk.

Methods

This case-control study comprised 6,517 patients with newly diagnosed SLE between 2006 and 2013. Patients without SLE were randomly selected as the control group and were matched at a case-control ratio of 1:20 by age, sex, and index year. All study individuals were traced from the index date back to their NTS exposure, other relevant covariates, or to the beginning of year 2000. Conditional logistic regression analysis was used to analyze the risk of SLE with adjusted odds ratios (aORs) and 95% confidence intervals (CIs) between the NTS and control groups.

Results

The mean age was 37.8 years in the case and control groups. Females accounted for 85.5%. The aOR of having NTS infection were significantly increased in SLE relative to controls (aOR, 9.20; 95% CI, 4.51-18.78) in 1:20 sex-age matching analysis and (aOR, 7.47; 95% CI=2.08-26.82) in propensity score matching analysis. Subgroup analysis indicated that the SLE risk was high among those who dwelled in rural areas; had rheumatoid arthritis, multiple sclerosis, or Sjogren’s syndrome; and developed intensive and severe NTS infection during admission.

Conclusions

Exposure to NTS infection is associated with the development of subsequent SLE in Taiwanese individuals. Severe NTS infection and other autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, or Sjogren’s syndrome also contributed to the risk of developing SLE.
Extracellular Lactate Acts as a Metabolic Checkpoint and Shapes Monocyte Function Time Dependently
Authors: Schenz Judith , Heilig Lena , Lohse Tim , Tichy Lucas , Bomans Katharina , Büttner Michael , Weigand Markus A. , Uhle Florian
Published: November 2021

Elevated blood lactate levels are frequently found in critically ill patients and thought to result from tissue hypoperfusion and cellular oxygen shortage. Considering the close relationship between immune cell function and intracellular metabolism, lactate is more than a glycolytic waste molecule but able to regulate the immune response. Our aim was to elucidate the temporal and mechanistic effect of extracellular lactate on monocytes. To this end, primary human monocytes and the human monocytic cell line MonoMac6 were stimulated with various toll-like-receptor agonists after priming with Na-L-lactate under constant pH conditions. As readout, cytokine production was measured, real-time assessment of intracellular energy pathways was performed, and intracellular metabolite concentrations were determined. Irrespective of the immunogenic stimulus, short-term Na-lactate-priming strongly reduced cytokine production capacity. Lactate and hexoses accumulated intracellularly and, together with a decreased glycolytic flux, indicate a lactate-triggered impairment of glycolysis. To counteract intracellular hyperglycemia, glucose is shunted into the branching polyol pathway, leading to sorbitol accumulation. In contrast, long-term priming with Na-L-lactate induced cellular adaption and abolished the suppressive effect. This lactate tolerance is characterized by a decreased cellular respiration due to a reduced complex-I activity. Our results indicate that exogenous lactate shapes monocyte function by altering the intracellular energy metabolism and acts as a metabolic checkpoint of monocyte activation.
Impact of Galectin-Receptor Interactions on Liver Pathology During the Erythrocytic Stage of Plasmodium berghei Malaria
Authors: Wu Yifan , Huang Shiguang , Xiao Siyu , He Jian , Lu Fangli
Published: November 2021

Hepatopathy is frequently observed in patients with severe malaria but its pathogenesis remains unclear. Galectins are evolutionarily conserved glycan-binding proteins with pleiotropic roles in innate and adaptive immune responses, and exhibit pivotal roles during Plasmodium spp. infection. Here, we analyzed the impact of blockage of galectin-receptor interactions by treatment with alpha (α)-lactose on liver immunopathology during the erythrocytic stage of malaria in mice infected with Plasmodium berghei ANKA (PbANKA). Our results found that compared with PbANKA-infected mice (malarial mice), blockage of galectin-receptor interactions led to decreased host survival rate and increased peripheral blood parasitemia; exacerbated liver pathology, increased numbers of CD68+ macrophages and apoptotic cells, and increased parasite burden in the livers on days 5 and 7 post infection (p.i.) as well as increased mRNA expression levels of galectin-9 (Gal-9) and its receptor, the T cell immunoglobulin domain and mucin domain protein 3 (Tim-3), interferon (IFN)α, IFNγ, and the triggering receptor expressed on myeloid cells (TREM)-1 in the livers or spleens of PbANKA-infected mice on day 7 p.i. Observed by transmission electron microscopy, the peritoneal macrophages isolated from malarial mice with α-lactose treatment had more pseudopodia than those from malarial mice. Measured by using quantitative real-time reverse transcription-polymerase chain reaction assay, the mRNA expression levels of Gal-9, IFNα, IFNβ, IFNγ, and TREM-1 were increased in the peritoneal macrophages isolated from malarial mice with α-lactose treatment in comparison of those from malarial mice. Furthermore, significant positive correlations existed between the mRNA levels of Gal-9 and Tim-3/IFNγ/TREM-1 in both the livers and the peritoneal macrophages, and between Gal-9 and Tim-3/TREM-1 in the spleens of malarial mice; significant positive correlations existed between the mRNA levels of Gal-9 and IFNγ in the livers and between Gal-9 and IFNα in the peritoneal macrophages from malarial mice treated with α-lactose. Our data suggest a potential role of galectin-receptor interactions in limiting liver inflammatory response and parasite proliferation by down-regulating the expressions of IFNα, IFNγ, and TREM-1 during PbANKA infection.
Newly Found Peacekeeper: Potential of CD8+ Tregs for Graft-Versus-Host Disease
Authors: Wang Weihao , Hong Tao , Wang Xiaoqi , Wang Rui , Du Yuxuan , Gao Qiangguo , Yang Shijie , Zhang Xi
Published: November 2021

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the most effective and potentially curative treatment for a variety of hematologic malignancies. However, graft-versus-host disease (GVHD) is a major obstacle that limits wide application of allo-HSCT, despite the development of prophylactic strategies. Owing to experimental and clinical advances in the field, GVHD is characterized by disruption of the balance between effector and regulatory immune cells, resulting in higher inflammatory cytokine levels. A reduction in regulatory T cells (Tregs) has been associated with limiting recalibration of inflammatory overaction and maintaining immune tolerance. Moreover, accumulating evidence suggests that immunoregulation may be useful for preventing GVHD. As opposed to CD4+ Tregs, the CD8+ Tregs population, which constitutes an important proportion of all Tregs, efficiently attenuates GVHD while sparing graft-versus-leukemic (GVL) effects. CD8+ Tregs may provide another form of cellular therapy for preventing GVHD and preserving GVL effects, and understanding the underlying mechanisms that different from those of CD4+ Tregs is significant. In this review, we summarize preclinical experiments that have demonstrated the role of CD8+ Tregs during GVHD and attempted to obtain optimized CD8+ Tregs. Notably, although optimized CD8+ Tregs have obvious advantages, more exploration is needed to determine how to apply them in the clinic.
The Zebrafish Antiapoptotic Protein BIRC2 Promotes Edwardsiella piscicida Infection by Inhibiting Caspases and Accumulating p53 in a p53 Transcription-Dependent and -Independent Manner
Authors: Cao Lu , Yan Dong , Xiao Jun , Feng Hao , Chang Ming Xian
Published: November 2021

IAPs (inhibitors of apoptosis) are endogenous caspase inhibitors with multiple biological activities. In the present study, we show functional characteristics of antiapoptotic protein BIRC2 (cIAP1) in response to Edwardsiella piscicida infection. Overexpression of BIRC2 in zebrafish larvae promoted the proliferation of E. piscicida, leading to a decreased larvae survival. The expression levels of caspases including casp3, casp8, and casp9 were significantly inhibited by BIRC2 overexpression in the case of E. piscicida infection. Treatment of zebrafish larvae microinjected with BIRC2 with the caspase activator PAC-1 completely blocked the negative regulation of BIRC2 on the E. piscicida infection, with the reduced inhibition on the casp3 and without inhibition on casp8 and casp9. In contrast to the regulation of BIRC2 on the caspases, BIRC2 overexpression significantly induced the expression of p53, especially at 24 hpi. In addition to the cytoplasmic p53 expression, BIRC2 overexpression also induced the expression of the nuclear p53 protein. Further analysis demonstrated that BIRC2 could interact and colocalize with p53 in the cytoplasm. The numbers of E. piscicida in larvae overexpressed with BIRC2 and treated with pifithrin-μ (an inhibitor of mitochondrial p53) or pifithrin-α (an inhibitor of p53 transactivation) were lower than those of larvae without pifithrin-μ or pifithrin-α treatment. Critically, the p53 inactivators pifithrin-μ and pifithrin-α had no significant effect on larval survival, but completely rescued larval survival for zebrafish microinjected with BIRC2 in the case of E. piscicida infection. Collectively, the present study suggest that piscine BIRC2 is a negative regulator for antibacterial immune response in response to the E. piscicida infection via inhibiting caspases, and accumulating p53 in a p53 transcription-dependent and -independent manner.
Summer Oxygen Dynamics on a Southern Arabian Gulf Coral Reef
Authors: de Verneil Alain , Burt John A. , Mitchell Matthew , Paparella Francesco
Published: November 2021

During the summer the Arabian Gulf is the world's warmest sea, also characterized by hypersalinity and extreme annual temperature fluctuations (12–35oC), making it marginal for coral growth. Yet extensive reefs occur in all eight nations bordering the Gulf. Here we present data demonstrating recurrent summer hypoxia events [oxygen concentration (O2) <2 mg l−1] at a reef in the southern Gulf. Currently these episodes are short enough (median 3 h, max 10 h) to preclude mass mortality. Will this always be the case? Predicting future Gulf hypoxia risk for coral reef ecosystems requires diagnosing the underlying causes driving the timing and magnitude of O2 swings. To this end, we compare our data with the output of a simple coupled 1-D water column/biogeochemical model of the reef environment. This allows us to give quantitative estimates of the O2 fluxes produced by photosynthesis both in the water column and within the coral framework, by respiration processes in the benthos, and from the atmosphere. We demonstrate the role of turbulent mixing, and in particular of tides, in shaping the temporal variability of the amplitude of the diel O2 cycle. We find that, in spite of significant turbulent mixing, which maintains the temperature vertically well-mixed, the biological O2 production and consumption is dominant over the atmospheric O2 flux, and is sufficient to generate vertical differences of 1 to 5 mg l−1 between the bottom and 1.5 m above it. While estimating future trends of hypoxia frequency will require further study, the present findings single out the relevant physical and biological processes (and their interplay) which deserve further scrutiny. The Gulf today experiences temperatures expected to occur across much of the tropics by the end of the century, and the observation of recurrent hypoxia events in the Gulf suggests that similar hypoxic phenomena may represent an important, but to date underappreciated, threat to the future of global coral reefs.
Advanced Development of Sustainable PECVD Semitransparent Photovoltaics: A Review
Authors: Kabongo G. L. , Mothudi B. M. , Dhlamini M. S.
Published: November 2021

Energy is the driving force behind the upcoming industrial revolution, characterized by connected devices and objects that will be perpetually supplied with energy. Moreover, the global massive energy consumption increase requires appropriate measures, such as the development of novel and improved renewable energy technologies for connecting remote areas to the grid. Considering the current prominent market share of unsustainable energy generation sources, inexhaustible and clean solar energy resources offer tremendous opportunities that, if optimally exploited, might considerably help to lessen the ever-growing pressure experienced on the grid nowadays. The R&D drive to develop and produce socio-economically viable solar cell technologies is currently realigning itself to manufacture advanced thin films deposition techniques for Photovoltaic solar cells. Typically, the quest for the wide space needed to deploy PV systems has driven scientists to design multifunctional nanostructured materials for semitransparent solar cells (STSCs) technologies that can fit in available household environmental and architectural spaces. Specifically, Plasma Enhanced Chemical Vapor Deposition (PECVD) technique demonstrated the ability to produce highly transparent coatings with the desired charge carrier mobility. The aim of the present article is to review the latest semi-transparent PV technologies that were impactful during the past decade with special emphasis on PECVD-related technologies. We finally draw some key recommendations for further technological improvements and sustainability.
Drastic Ce3+ Insertion Enhancement in YAG Garnet Nanocrystals Through a Solvothermal Route
Authors: Cantarano Alexandra , Testemale Denis , Homeyer Estelle , Okuno Hanako , Potdevin Audrey , Dujardin Christophe , Ibanez Alain , Dantelle Geraldine
Published: November 2021

Y3Al5O12 (YAG) nanocrystals have been synthesized by a modified solvothermal method (300°C) allowing the incorporation of cerium ions in much larger proportion (up to 30 mol.% with respect to yttrium ions) than ever published. The reasons are the nanometric size of the produced nanocrystals, allowing to accommodate Ce3+ ions in the rigid YAG structure thanks to the presence of local distortions, and also the soft synthesis route, at low temperatures and far from the thermodynamic equilibrium, which favors the cerium insertion. As a consequence, Ce3+ photoluminescence spectrum can be tuned with the doping concentration, from 541 nm for low Ce3+ concentration to 580 nm for a cerium concentration of 30 mol.%. The internal quantum yield reaches 40 ± 5% before decreasing due to concentration quenching. The nanocrystal brightness, which combines the internal quantum yield and the cerium concentration, has been found optimal for a doping of 2 mol.% Ce3+.
A Solar-Blind Ultraviolet Photodetector With Graphene/MgZnO/GaN Vertical Structure
Authors: Wang Zhao , Lin Jun , Wei Xuan , Zheng Wei , Hu Qichang
Published: November 2021

Graphene (Gr) has high transmittance to ultraviolet (UV) light and high mobility, which can effectively collect and transfer carriers. In this work, MgZnO (MZO) films were grown on the surface of the p-GaN by magnetron sputtering. A heterojunction solar-blind UV detector with Gr/MZO/GaN structure was constructed by introducing Gr as the window layer film. The test results show that the device has excellent detection ability for solar-blind UV light. The light response cut-off edge of the device is 263 nm, under the illumination of 255 nm and the bias voltage of −5 V, the responsivity is 14.6 mA/W, the rise time is 0.79 s, the decay time is 0.2 s, and the external quantum efficiency is 71.1%. The importance of this work lies in providing a reference for the application of Gr-based photodetectors.
The MUC5B Promoter Polymorphism Associates With Severe COVID-19 in the European Population
Authors: van Moorsel Coline H. M. , van der Vis Joanne J. , Duckworth Anna , Scotton Chris J. , Benschop Claudia , Ellinghaus David , Ruven Henk J. T. , Quanjel Marian J. R. , Grutters Jan C.
Published: November 2021

Background: Diversity in response on exposure to severe acute respiratory syndrome coronavirus 2 may be related to the innate immune response in the elderly. The mucin MUC5B is an important component of the innate immune response and expression levels are associated with the MUC5B promoter polymorphism, rs35705950. The high expressing T-allele is a risk allele for the non-infectious aging lung disease idiopathic pulmonary fibrosis (IPF). We investigated if MUC5B rs35705950 associates with severe COVID-19.

Methods: In this retrospective candidate gene case-control study we recruited 108 Dutch patients (69% male, median age 66 years, 77% white) requiring hospitalization for COVID-19 (22% ICU stay, 24% died). For validation, genotypes were obtained from the UK-Biobank (n = 436, 57% male, median age 70 years, 27% died), for replication data from the severe COVID-19 GWAS group from Italy (n = 835) and Spain (n = 775) was used, each with a control cohort (n = 356,735, n = 1,255, n = 950, respectively). MUC5B association analysis was performed including adjustment for age and sex.

Results: The rs35705950 T-allele frequency was significantly lower in Dutch white patients (n = 83) than in controls (0.04 vs. 0.10; p = 0.02). This was validated in the UK biobank cohort (0.08 vs. 0.11; p = 0.001). While age and sex differed significantly between cases and control, comparable results were obtained with age and sex as confounding variables in a multivariate analysis. The association was replicated in the Italian (p = 0.04), and Spanish (p = 0.03) case-control cohorts. Meta-analysis showed a negative association for the T-allele with COVID-19 (OR = 0.75 (CI: 0.67–0.85); p = 6.63 × 10−6).

Conclusions: This study shows that carriage of the T-allele of MUC5B rs35705950 confers protection from development of severe COVID-19. Because the T-allele is a known risk allele for IPF, this study provides further evidence for the existence of trade-offs between optimal mucin expression levels in the aging lung.
The Role of General Practice in Complex Health Care Systems
Authors: Schmalstieg-Bahr Katharina , Popert Uwe Wolfgang , Scherer Martin
Published: November 2021

According to the WHO, in a complex system, “there are so many interacting parts that it is difficult (…), to predict the behavior of the system based on knowledge of its component parts. “In countries without general practitioner (GP)-gatekeeping, the number of possible interactions and therefore the complexity increases. Patients may consult any doctor without contacting their GP. Family medicine core values, e.g., comprehensive care, and core tasks, e.g., care coordination, might be harder to implement and maintain. How are GPs perceived and how do they perceive themselves if no GP-gatekeeping exists? Does the absence of any GP-gatekeeping influence family medicine core values? A PubMed and Cochrane search was performed. The results are summarized in form of a narrative review. Four perspectives regarding the GP's role were identified. The GPs' self-perception regarding family medicine core values and tasks is independent of their function as gatekeepers, but they appreciate this role. Patient satisfaction is also independent of the health care system. Depending on the acquisition of income, specialists have different opinions of GP-gatekeeping. Policymakers want GPs to play a central role within the health care system, but do not commit to full gatekeeping. The GPs and policymakers emphasize the importance of family medicine specialty training. Further international studies are needed to determine if family medicine core values and tasks can be better accomplished by GP-gatekeeping. Specialty training should be mandatory in all countries to enable GPs to fulfill these values and tasks and to act as coordinators and/or gatekeepers.
Advances and Current Clinical Applications of Anterior Segment Optical Coherence Tomography Angiography
Authors: Luo Man , Li Yiqing , Zhuo Yehong
Published: November 2021

Optical coherence tomography angiography (OCTA) is the most relevant evolution based on optical coherence tomography (OCT). OCTA can present ocular vasculature, show detailed morphology for assessment, and quantify vessel parameters without intravenous dye agent. Research on the anterior segment OCTA (AS-OCTA) is only in its initial phase, and its advances in clinical diagnosis and treatment efficacy evaluations require a detailed comparison to traditional imaging methods. In this review of AS-OCTA, we summarize its technical features, imaging advances, current clinical applications in various eye diseases, as well as its limitations and potential future directions. AS-OCTA offers potential advantages in ophthalmic imaging, and with further development it could become a common tool in the near future.
Hfq Regulates Efflux Pump Expression and Purine Metabolic Pathway to Increase Trimethoprim Resistance in Aeromonas veronii
Authors: Wang Dan , Li Hong , Ma Xiang , Tang Yanqiong , Tang Hongqian , Huang Dongyi , Lin Min , Liu Zhu
Published: November 2021

Aeromonas veronii (A. veronii) is a zoonotic pathogen. It causes clinically a variety of diseases such as dysentery, bacteremia, and meningitis, and brings huge losses to aquaculture. A. veronii has been documented as a multiple antibiotic resistant bacterium. Hfq (host factor for RNA bacteriophage Qβ replication) participates in the regulations of the virulence, adhesion, and nitrogen fixation, effecting on the growth, metabolism synthesis and stress resistance in bacteria. The deletion of hfq gene in A. veronii showed more sensitivity to trimethoprim, accompanying by the upregulations of purine metabolic genes and downregulations of efflux pump genes by transcriptomic data analysis. Coherently, the complementation of efflux pump-related genes acrA and acrB recovered the trimethoprim resistance in Δhfq. Besides, the accumulations of adenosine and guanosine were increased in Δhfq in metabonomic data. The strain Δhfq conferred more sensitive to trimethoprim after appending 1 mM guanosine to M9 medium, while wild type was not altered. These results demonstrated that Hfq mediated trimethoprim resistance by elevating efflux pump expression and degrading adenosine, and guanosine metabolites. Collectively, Hfq is a potential target to tackle trimethoprim resistance in A. veronii infection.
Identification of Two Molecular Subtypes of Hepatocellular Carcinoma Based on Dysregulated Immune LncRNAs
Authors: Lin Hongsheng , Xie Yangyi , Kong Yinzhi , Yang Li , Li Mingfen
Published: November 2021

Long non-coding RNAs (lncRNAs) as important regulators of gene expression also have critical functions in immune regulation. This study identified lncRNA modulators of immune-related pathways as biomarkers for hepatocellular carcinoma (HCC). The profile of lncRNA regulation in immune pathways in HCC was comprehensively mapped. To determine lncRNAs with immunomodulatory functions specific to HCC, the enrichment of lncRNAs in a collection of 17 immune functions was calculated applying gene set enrichment analysis (GSEA). Unsupervised clustering of samples were performed in the R package ConsensusClusterPlus to analyze subtype survival and immunological characteristics. The enrichment of 3,134 lncRNA–immune pathway pairs in both diseased and normal samples showed a total of 1,984 immunoregulatory functional lncRNAs specific to HCC only. In addition, 18 immune-related lncRNAs were disordered in HCC and were significantly associated with immune cell infiltration. Functional enrichment analysis indicated that the 18 dysregulated immune lncRNAs were enriched in cytokines, cytokine receptors, TGFb family members, TNF family members, and TNF family member receptor pathways. Two molecular subtypes of hepatocellular carcinoma were identified based on 18 dysregulated immune lncRNAs. Immunological profiling showed that subtype 1 samples with higher levels of cytokine response had a better survival, but subtype 2 samples with higher levels of tumor proliferation had poorer survival. This study identified 18 HCC-specific dysregulated immune lncRNAs and two HCC molecular subtypes with significant prognostic differences and immune characteristics. The current findings help understand the function of lncRNAs and promote the identification of immunotherapy targets.
Potential Clinical Applications of Exosomal Circular RNAs: More than Diagnosis
Authors: Molibeli Kearabetsoe Matseliso , Hu Rong , Liu Yuze , Xiong Dehui , Tang Lijun
Published: November 2021

Exosomes are small vesicles derived from cells used as cell-to-cell communication goods in numerous diseases including tumorigenesis, neurological diseases, cardiovascular diseases and other diseases. Circular RNAs (circRNAs) are an innovative constituent of non-coding endogenous RNAs generated through backsplicing, catalyzed by RNA polymerase Ⅱ. These non-coding RNAs have been suggested to control gene expression through miRNA sponging, RNA-binding protein regulation and translational capabilities. Genome-wide RNA sequence analyses observed that circRNAs were stably improved in exosomes in association to parental cells. Little attention has been dedicated to exosomal circRNAs (exo-circRNAs). However, research has demonstrated that exo-circRNAs may have important regulatory functions because of their stability in cells and within exosomes. If well understood, the precise roles and mechanisms of exo-circRNAs might surge the impending clinical applications of these molecules as markers in the identification, prediction and treatment of various diseases. In this review, we outline recent findings regarding exo-circRNAs which includes their functions and highlights their potential applications and therapeutic targets in human diseases.
Carotid Artery Perivascular Adipose Tissue Density Relates to Recanalization and Clinical Outcome After Mechanical Thrombectomy
Authors: Jin Jiaolei , Huang Rui , Chen Qiuyue , Ke Boxi , Tao Taotao , Zhao Rong , He Xinwei
Published: November 2021

Background: Perivascular adipose tissue (PVAT) imaging can be used in clinical practice as a surrogate marker of vascular disease. We aimed to analyze the association between the density of carotid artery PVAT and clinical features and outcomes in stroke patients treated with mechanical thrombectomy.

Methods: A total of 183 consecutive patients treated with mechanical thrombectomy due to anterior circulation large vessel occlusion were retrospectively included from January 2016 to May 2021. The density of carotid artery PVAT was evaluated by preoperative computed tomography angiography. Successful arterial recanalization was defined as a modified Thrombolysis in Cerebral Infarction score of 2b-3 on the final angiographic examination. Poor functional outcome was defined as a modified Rankin Scale (mRS) score > 2 at 3 months after stroke. We assessed the independent effect of carotid artery PVAT density on revascularization, functional outcome, and mortality using logistic regression models adjusted for relevant confounders.

Results: Patients with large artery atherosclerotic stroke have higher carotid artery PVAT density than patients with other stroke etiologies (–65.82 ± 12.96 vs. –75.77 ± 13.44, P < 0.001). Higher carotid artery PVAT density was associated with unsuccessful recanalization [adjusted odds ratio (AOR) (95% CI), 2.968 (1.292, 6.819), P = 0.010], and poor outcome [AOR (95% CI), 2.704 (1.610, 4.541), P < 0.001] and mortality [AOR (95% CI), 1.894 (1.040, 3.449), P = 0.037] at 3 months in stroke patients treated with thrombectomy.

Conclusion: Higher carotid artery PVAT density before mechanical thrombectomy is an indicator of worse postprocedural arterial revascularization and a worse functional outcome in acute stroke patients.
Neuromodulation and Individuality
Authors: Maloney Ryan T.
Published: November 2021

Within populations, individuals show a variety of behavioral preferences, even in the absence of genetic or environmental variability. Neuromodulators affect these idiosyncratic preferences in a wide range of systems, however, the mechanism(s) by which they do so is unclear. I review the evidence supporting three broad mechanisms by which neuromodulators might affect variability in idiosyncratic behavioral preference: by being a source of variability directly upstream of behavior, by affecting the behavioral output of a circuit in a way that masks or accentuates underlying variability in that circuit, and by driving plasticity in circuits leading to either homeostatic convergence toward a given behavior or divergence from a developmental setpoint. I find evidence for each of these mechanisms and propose future directions to further understand the complex interplay between individual variability and neuromodulators.
Locomotion Control With Frequency and Motor Pattern Adaptations
Authors: Thor Mathias , Strohmer Beck , Manoonpong Poramate
Published: November 2021

Existing adaptive locomotion control mechanisms for legged robots are usually aimed at one specific type of adaptation and rarely combined with others. Adaptive mechanisms thus stay at a conceptual level without their coupling effect with other mechanisms being investigated. However, we hypothesize that the combination of adaptation mechanisms can be exploited for enhanced and more efficient locomotion control as in biological systems. Therefore, in this work, we present a central pattern generator (CPG) based locomotion controller integrating both a frequency and motor pattern adaptation mechanisms. We use the state-of-the-art Dual Integral Learner for frequency adaptation, which can automatically and quickly adapt the CPG frequency, enabling the entire motor pattern or output signal of the CPG to be followed at a proper high frequency with low tracking error. Consequently, the legged robot can move with high energy efficiency and perform the generated locomotion with high precision. The versatile state-of-the-art CPG-RBF network is used as a motor pattern adaptation mechanism. Using this network, the motor patterns or joint trajectories can be adapted to fit the robot's morphology and perform sensorimotor integration enabling online motor pattern adaptation based on sensory feedback. The results show that the two adaptation mechanisms can be combined for adaptive locomotion control of a hexapod robot in a complex environment. Using the CPG-RBF network for motor pattern adaptation, the hexapod learned basic straight forward walking, steering, and step climbing. In general, the frequency and motor pattern mechanisms complement each other well and their combination can be seen as an essential step toward further studies on adaptive locomotion control.
Dabigatran Reversal With Idarucizumab and In-Hospital Mortality in Intracranial Hemorrhage: A Systematic Review of Real-Life Data From Case Reports and Case Series
Authors: Frol Senta , Sagris Dimitrios , Šabovič Mišo , Ntaios George , Oblak Janja Pretnar
Published: November 2021

Background: Intracranial hemorrhage is a severe and possibly fatal consequence of anticoagulation therapy. Idarucizumab is used in dabigatran-treated patients suffering from intracranial hemorrhage (ICH) to reverse the anticoagulant effect of dabigatran. Systematic review of real-life mortality in these patients is missing.

Objectives: A review of all published dabigatran-related ICH cases treated with idarucizumab was performed. We aimed to estimate in-hospital mortality rate in these patients.

Method: We searched PubMed and Scopus for all published cases of ICH in idarucizumab/dabigatran-treated patients until May 15, 2021. The assessed outcome was in-hospital mortality.

Results: We identified six eligible studies (case series) with 386 patients and 54 single case reports. In-hospital mortality rate was 11.4% in the case series and 9.7% in the case reports.

Conclusions: Our analysis provides clinically relevant quantitative data regarding in-hospital mortality in idarucizumab/dabigatran-treated patients with ICH, which is estimated to be 9.7–11.4%.
The Effect of Sex and Wealth on Population Attributable Risk Factors for Dementia in South Africa
Authors: Bobrow Kirsten , Hoang Tina , Barnes Deborah E. , Gardner Raquel C. , Allen Isabel E. , Yaffe Kristine
Published: November 2021

Background and Aims: South Africa is a middle-income country with high levels of income inequality and a rapidly aging population and increasing dementia prevalence. Little is known about which risk factors for dementia are important and how they differ by social determinants of health as well as key demographic characteristics such as sex and wealth. We sought to calculate the population attributable risks (PARs) for established potentially modifiable risk factors for dementia among these different groups.

Methods: We obtained risk factor prevalence from population-based surveys for established dementia risk factors (diabetes, midlife hypertension, midlife obesity, physical inactivity, depression, smoking, low educational attainment, social isolation). We used relative risk estimates reported in previous meta-analyses and estimated PARs using Levin's formula and accounting for communality. We tested for one-way and two-way interactions by sex and wealth using Pearson's χ2. In stratified analyses, we performed tests for trend using logistic regression.

Results: The prevalence of established risk factors for dementia ranged from 5% for depression to 64% for low education. After accounting for communality, the risk factors contributing the greatest PAR were low education (weighted PAR 12%, 95% CI 7% to 18%), physical inactivity (9, 5–14%), and midlife hypertension (6, 5–14%). Together, 45% of dementia cases may be attributable to modifiable risk factors (95% CI 25–59%). We found significant interactions (p < 0.005) between sex, wealth, or both (sex * wealth) and each risk factor except social isolation and physical activity. Low education was inversely associated with wealth in both male and female. The PAR for midlife hypertension, obesity, and diabetes was associated with increasing wealth, and was higher in female. In contrast, the PAR for smoking was higher in male (8% vs. 2%) and was associated with increasing wealth among female only. We found that either a strategy of large reductions in selected risk factors with the highest PAR (midlife hypertension, smoking, physical inactivity) or small reductions across all risk factors could potentially reduce dementia cases by as many as 250,000 by 2050.

Discussions: The potential impact on dementia risk by decreasing exposure to established dementia risk factors is large and differs by sex and social determinants of health like wealth. Risk factor PAR should inform national and local health policy dementia initiatives in South Africa including which risk factors to target in the whole population and which to target in high-risk groups for maximum public health benefit.
Functional Recovery and Serum Angiogenin Changes According to Intensity of Rehabilitation Therapy After Stroke
Authors: Garcia-Rodriguez Nicolás , Rodriguez Susana , Tejada Pedro Ignacio , Miranda-Artieda Zuberoa Maite , Ridao Natalia , Buxó Xavi , Pérez-Mesquida María Engracia , Beseler Maria Rosario , Salom Juan B. , Pérez Laura M. , Inzitari Marco , Otero-Villaverde Sergio , Martin-Mourelle Rosa , Molleda Mercedes , Quintana Manuel , Olivé-Gadea Marta , Penalba Anna , Rosell Anna
Published: November 2021

Background: Rehabilitation is still the only treatment available to improve functional status after the acute phase of stroke. Most clinical guidelines highlight the need to design rehabilitation treatments considering starting time, intensity, and frequency, according to the tolerance of the patient. However, there are no homogeneous protocols and the biological effects are under investigation.

Objective: To investigate the impact of rehabilitation intensity (hours) after stroke on functional improvement and serum angiogenin (ANG) in a 6-month follow-up study.

Methods: A prospective, observational, longitudinal, and multicenter study with three cohorts: strokes in intensive rehabilitation therapy (IRT, minimum 15 h/week) vs. conventional therapy (NO-IRT, <15 h/week), and controls subjects (without known neurological, malignant, or inflammatory diseases). A total of seven centers participated, with functional evaluations and blood sampling during follow-up. The final cohort includes 62 strokes and 43 controls with demographic, clinical, blood samples, and exhaustive functional monitoring.

Results: The median (IQR) number of weekly hours of therapy was different: IRT 15 (15–16) vs. NO-IRT 7.5 (5–9), p < 0.01, with progressive and significant improvements in both groups. However, IRT patients showed earlier improvements (within 1 month) on several scales (CAHAI, FMA, and FAC; p < 0.001) and the earliest community ambulation achievements (0.89 m/s at 3 months). There was a significant difference in ANG temporal profile between the IRT and NO-IRT groups (p < 0.01). Additionally, ANG was elevated at 1 month only in the IRT group (p < 0.05) whereas it decreased in the NO-IRT group (p < 0.05).

Conclusions: Our results suggest an association of rehabilitation intensity with early functional improvements, and connect the rehabilitation process with blood biomarkers.
Using Transcranial Electrical Stimulation in Audiological Practice: The Gaps to Be Filled
Authors: Nooristani Mujda , Augereau Thomas , Moïn-Darbari Karina , Bacon Benoit-Antoine , Champoux François
Published: November 2021

The effects of transcranial electrical stimulation (tES) approaches have been widely studied for many decades in the motor field, and are well known to have a significant and consistent impact on the rehabilitation of people with motor deficits. Consequently, it can be asked whether tES could also be an effective tool for targeting and modulating plasticity in the sensory field for therapeutic purposes. Specifically, could potentiating sensitivity at the central level with tES help to compensate for sensory loss? The present review examines evidence of the impact of tES on cortical auditory excitability and its corresponding influence on auditory processing, and in particular on hearing rehabilitation. Overall, data strongly suggest that tES approaches can be an effective tool for modulating auditory plasticity. However, its specific impact on auditory processing requires further investigation before it can be considered for therapeutic purposes. Indeed, while it is clear that electrical stimulation has an effect on cortical excitability and overall auditory abilities, the directionality of these effects is puzzling. The knowledge gaps that will need to be filled are discussed.
Scarcity Mindset Neuro Network Decoding With Reward: A Tree-Based Model and Functional Near-Infrared Spectroscopy Study
Authors: Jiang Xiaowei , Zhou Chenghao , Ao Na , Gu Wenke , Li Jingyi , Chen Yanan
Published: November 2021

Resource scarcity imposes challenging demands on the human cognitive system. Insufficient resources cause the scarcity mindset to affect cognitive performance, while reward enhances cognitive function. Here, we examined how reward and scarcity simultaneously contribute to cognitive performance. Experimental manipulation to induce a polar scarcity mindset and reward conditions within participants under functional near-infrared spectroscopy (fNIRS) recording was implemented to explore the mechanism underlying the scarcity mindset and reward in terms of behavior and neurocognition. Participants showed decreased functional connectivity from the dorsolateral prefrontal cortex (DLPFC) to the ventrolateral prefrontal cortex (VLPFC) with a scarcity mindset, a region often implicated in cognitive control. Moreover, under reward conditions, the brain activation of the maximum total Hb bold signal was mainly located in the left hemisphere [channels 1, 3, and 4, left ventrolateral prefrontal cortex (L-VLPFC) and channel 6, left dorsolateral prefrontal cortex (L-DLPFC)], and there was also significant brain activation of the right dorsolateral prefrontal cortex (R-DLPFC) in the right hemisphere (channel 17). Furthermore, these data indicate the underlying neural changes of the scarcity mentality and demonstrate that brain activities may underlie reward processing. Additionally, the base-tree machine learning model was trained to detect the mechanism of reward function in the prefrontal cortex (PFC). According to SHapley Additive exPlanations (SHAP), channel 8 contributed the most important effect, as well as demonstrating a high-level interrelationship with other channels.
Multimodal Ensemble Deep Learning to Predict Disruptive Behavior Disorders in Children
Authors: Menon Sreevalsan S. , Krishnamurthy K.
Published: November 2021

Oppositional defiant disorder and conduct disorder, collectively referred to as disruptive behavior disorders (DBDs), are prevalent psychiatric disorders in children. Early diagnosis of DBDs is crucial because they can increase the risks of other mental health and substance use disorders without appropriate psychosocial interventions and treatment. However, diagnosing DBDs is challenging as they are often comorbid with other disorders, such as attention-deficit/hyperactivity disorder, anxiety, and depression. In this study, a multimodal ensemble three-dimensional convolutional neural network (3D CNN) deep learning model was used to classify children with DBDs and typically developing children. The study participants included 419 females and 681 males, aged 108–131 months who were enrolled in the Adolescent Brain Cognitive Development Study. Children were grouped based on the presence of DBDs (n = 550) and typically developing (n = 550); assessments were based on the scores from the Child Behavior Checklist and on the Schedule for Affective Disorders and Schizophrenia for School-age Children-Present and Lifetime version for DSM-5. The diffusion, structural, and resting-state functional magnetic resonance imaging (rs-fMRI) data were used as input data to the 3D CNN. The model achieved 72% accuracy in classifying children with DBDs with 70% sensitivity, 72% specificity, and an F1-score of 70. In addition, the discriminative power of the classifier was investigated by identifying the cortical and subcortical regions primarily involved in the prediction of DBDs using a gradient-weighted class activation mapping method. The classification results were compared with those obtained using the three neuroimaging modalities individually, and a connectome-based graph CNN and a multi-scale recurrent neural network using only the rs-fMRI data.
Stability of AI-Enabled Diagnosis of Parkinson’s Disease: A Study Targeting Substantia Nigra in Quantitative Susceptibility Mapping Imaging
Authors: Xiao Bin , He Naying , Wang Qian , Shi Feng , Cheng Zenghui , Haacke Ewart Mark , Yan Fuhua , Shen Dinggang
Published: November 2021

Purpose: Parkinson’s disease (PD) diagnosis algorithms based on quantitative susceptibility mapping (QSM) and image algorithms rely on substantia nigra (SN) labeling. However, the difference between SN labels from different experts (or segmentation algorithms) will have a negative impact on downstream diagnostic tasks, such as the decrease of the accuracy of the algorithm or different diagnostic results for the same sample. In this article, we quantify the accuracy of the algorithm on different label sets and then improve the convolutional neural network (CNN) model to obtain a high-precision and highly robust diagnosis algorithm.

Methods: The logistic regression model and CNN model were first compared for classification between PD patients and healthy controls (HC), given different sets of SN labeling. Then, based on the CNN model with better performance, we further proposed a novel “gated pooling” operation and integrated it with deep learning to attain a joint framework for image segmentation and classification.

Results: The experimental results show that, with different sets of SN labeling that mimic different experts, the CNN model can maintain a stable classification accuracy at around 86.4%, while the conventional logistic regression model yields a large fluctuation ranging from 78.9 to 67.9%. Furthermore, the “gated pooling” operation, after being integrated for joint image segmentation and classification, can improve the diagnosis accuracy to 86.9% consistently, which is statistically better than the baseline.

Conclusion: The CNN model, compared with the conventional logistic regression model using radiomics features, has better stability in PD diagnosis. Furthermore, the joint end-to-end CNN model is shown to be suitable for PD diagnosis from the perspectives of accuracy, stability, and convenience in actual use.
Role of the Autonomic Nervous System in Mechanism of Energy and Glucose Regulation Post Bariatric Surgery
Authors: An Zhibo , Wang Haiying , Mokadem Mohamad
Published: November 2021

Even though lifestyle changes are the mainstay approach to address obesity, Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are the most effective and durable treatments facing this pandemic and its associated metabolic conditions. The traditional classifications of bariatric surgeries labeled them as “restrictive,” “malabsorptive,” or “mixed” types of procedures depending on the anatomical rearrangement of each one of them. This conventional categorization of bariatric surgeries assumed that the “restrictive” procedures induce their weight loss and metabolic effects by reducing gastric content and therefore having a smaller reservoir. Similarly, the “malabsorptive” procedures were thought to induce their main energy homeostatic effects from fecal calorie loss due to intestinal malabsorption. Observational data from human subjects and several studies from rodent models of bariatric surgery showed that neither of those concepts is completely true, at least in explaining the multiple metabolic changes and the alteration in energy balance that those two surgeries induce. Rather, neuro-hormonal mechanisms have been postulated to underly the physiologic effects of those two most performed bariatric procedures. In this review, we go over the role the autonomic nervous system plays- through its parasympathetic and sympathetic branches- in regulating weight balance and glucose homeostasis after SG and RYGB.
When Are Depolarizing GABAergic Responses Excitatory?
Authors: Kilb Werner
Published: November 2021

The membrane responses upon activation of GABA(A) receptors critically depend on the intracellular Cl− concentration ([Cl−]i), which is maintained by a set of transmembrane transporters for Cl−. During neuronal development, but also under several pathophysiological conditions, the prevailing expression of the Cl− loader NKCC1 and the low expression of the Cl− extruder KCC2 causes elevated [Cl−]i, which result in depolarizing GABAergic membrane responses. However, depolarizing GABAergic responses are not necessarily excitatory, as GABA(A) receptors also reduces the input resistance of neurons and thereby shunt excitatory inputs. To summarize our knowledge on the effect of depolarizing GABA responses on neuronal excitability, this review discusses theoretical considerations and experimental studies illustrating the relation between GABA conductances, GABA reversal potential and neuronal excitability. In addition, evidences for the complex spatiotemporal interaction between depolarizing GABAergic and glutamatergic inputs are described. Moreover, mechanisms that influence [Cl−]i beyond the expression of Cl− transporters are presented. And finally, several in vitro and in vivo studies that directly investigated whether GABA mediates excitation or inhibition during early developmental stages are summarized. In summary, these theoretical considerations and experimental evidences suggest that GABA can act as inhibitory neurotransmitter even under conditions that maintain substantial depolarizing membrane responses.