Faculty Bibliography

Cortical networks are complex systems of a great many interconnected neurons that operate from collective dynamical states. To understand how cortical neural networks function, it is important to identify their common dynamical operating states from the probabilistic viewpoint. Probabilistic characteristics of these operating states often underlie network functions. Here, using multi-electrode data from three separate experiments, we identify and characterize a cortical operating state (the "probability polling" or "p-polling" state), common across mouse and monkey with different behaviors. If the interaction among neurons is weak, the p-polling state provides a quantitative understanding of how the high dimensional probability distribution of firing patterns can be obtained by the low-order maximum entropy formulation, effectively utilizing a low dimensional stimulus-coding structure. These results show evidence for generality of the p-polling state and in certain situations its advantage of providing a mathematical validation for the low-order maximum entropy principle as a coding strategy.

Cancer cells secrete pro-nociceptive mediators that sensitize adjacent sensory neurons and cause pain. Identification and characterization of these mediators could pinpoint novel targets for cancer pain treatment. In the present study we identified candidate genes in cancer cell lines that encode for secreted or cell surface proteins that may drive nociception. To undertake this work, we utilized an acute cancer pain mouse model, transcriptomic analysis of publicly available human tumor-derived cell line data, and a literature review. Cancer cell line supernatants were assigned a phenotype based on evoked nociceptive behavior in an acute cancer pain mouse model. We compared gene expression data from nociceptive and non-nociceptive cell lines. Our analyses revealed differentially expressed genes (DEGs) and pathways; many of the identified genes were not previously associated with cancer pain signaling. Epidermal growth factor receptor (EGFR) and disintegrin metalloprotease domain 17 (ADAM17) were identified as potential targets among the DEGs. We found that the nociceptive cell lines contained significantly more ADAM17 protein in the cell culture supernatant compared to non-nociceptive cell lines. Cytoplasmic EGFR was present in almost all (>90%) tongue primary afferent neurons in mice. Monoclonal antibody against EGFR, cetuximab, inhibited cell line supernatant-induced nociceptive behavior in an acute oral cancer pain mouse model. We infer from these data that ADAM17-EGFR signaling is involved in cancer mediator-induced nociception. The differentially expressed genes and their secreted protein products may serve as candidate therapeutic targets for oral cancer pain and warrant further evaluation.

Primates and rodents, which descended from a common ancestor around 90 million years ago¹, exhibit profound differences in behaviour and cognitive capacity; the cellular basis for these differences is unknown. Here we use single-nucleus RNA sequencing to profile RNA expression in 188,776 individual interneurons across homologous brain regions from three primates (human, macaque and marmoset), a rodent (mouse) and a weasel (ferret). Homologous interneuron types-which were readily identified by their RNA-expression patterns-varied in abundance and RNA expression among ferrets, mice and primates, but varied less among primates. Only a modest fraction of the genes identified as 'markers' of specific interneuron subtypes in any one species had this property in another species. In the primate neocortex, dozens of genes showed spatial expression gradients among interneurons of the same type, which suggests that regional variation in cortical contexts shapes the RNA expression patterns of adult neocortical interneurons. We found that an interneuron type that was previously associated with the mouse hippocampus-the 'ivy cell', which has neurogliaform characteristics-has become abundant across the neocortex of humans, macaques and marmosets but not mice or ferrets. We also found a notable subcortical innovation: an abundant striatal interneuron type in primates that had no molecularly homologous counterpart in mice or ferrets. These interneurons expressed a unique combination of genes that encode transcription factors, receptors and neuropeptides and constituted around 30% of striatal interneurons in marmosets and humans.

Head and neck tumors can affect afferent baroreceptor neurons and either interrupt or intermittently increase their signaling, causing blood pressure to become erratic. When the afferent fibers of the baroreflex are injured by surgery or radiotherapy or fail to develop as in familial dysautonomia, their sensory information is no longer present to regulate arterial blood pressure, resulting in afferent baroreflex failure. When the baroreflex afferents are abnormally activated, such as by paragangliomas in the neck, presumably by direct compression, they trigger acute hypotension and bradycardia and frequently syncope, by a mechanism similar to the carotid sinus syndrome. We describe our observations in a large series of 23 patients with afferent baroreflex dysfunction and the cardiovascular autonomic features that arise when the sensory baroreceptor neurons are injured or compressed. The management of afferent baroreceptor dysfunction is limited, but pharmacological strategies can mitigate blood pressure swings, improve symptoms, and may reduce hypertensive organ damage. Although rare, the prevalence of afferent baroreflex dysfunction appears to be increasing in middle-aged men due to human papillomavirus related oropharyngeal cancer.

Objective; To analyze a case of complex multisite carbapenems-resistant Klebsiella pneumoniae (CRKP) infection,and to evaluate the rationality of the treatment scheme,so as to provide reference for rational use of drugs.
Method(s): The clinical and laboratory data of the patient were collected,and the clinical efficacy was observed,laboratory indexes and the results of etiological examination were compared, treatment effect was evaluated and relevant literature was reviewed. Results and
Conclusion(s): In the treatment of the patient,meropenem,amikacin combined with fosfomycin were used. Literature retrieval revealed that there were many kinds of antimicrobial therapy options for CRKP infection, but cure rate was not clear. The prevalence of CRKP was more feasible in the intensive care unit(ICU). Reducing irrational use of broad-spectrum antibacterials and unnecessary invasive manipulation were effective strategies for the control of CRKP prevalence and reduction of economic burden on patients.
Copyright

OBJECTIVES/OBJECTIVE:To investigate the potential value of adding a tagged three-chamber (3Ch) cine to clinical hypertrophic cardiomyopathy (HCM) magnetic resonance imaging (MRI) protocols, including to help distinguish HCM patients with regionally impaired cardiac function. METHODS:Forty-eight HCM patients, five patients with "septal knuckle" (SK), and 20 healthy volunteers underwent MRI at 1.5T; a tagged 3Ch cine was added to the protocol. Regional strain, myocardial wall thickness, and mitral valve leaflet lengths were measured in the 3Ch view. RESULTS:In HCM, we found a reduced tangential strain with decreased diastolic relaxation in both hypertrophied (p = 0.003) and remote segments (p = 0.035). Strain in the basal septum correlated with the length of the coaptation zone + residual leaflet (r = 0.48, p < 0.001). In the basal free wall, patients with SK had faster relaxation compared to HCM patients with septal hypertrophy. DISCUSSION/CONCLUSIONS:The 3Ch tagged MRI sequence provides useful information for the examination of suspected HCM patients, with minimal additional time cost. Local wall function is closely associated with morphological changes of the mitral apparatus measured in the same plane and may provide insights into mechanisms of obstruction. The additional strain information may be helpful when analyzing local myocardial wall motion patterns in the presence of SK.

Reports an error in "Meditation effect in changing functional integrations across large-scale brain networks: Preliminary evidence from a meta-analysis of seed-based functional connectivity" by Yang-Qian Shen, Hui-Xia Zhou, Xiao Chen, Francisco Xavier Castellanos and Chao-Gan Yan (Journal of Pacific Rim Psychology, 2020[Mar][3], Vol 14[e10]). In the original article, there was an error in the abstract. The correction is given in the erratum. (The following abstract of the original article appeared in record 2020-55329-001). Meditation is a type of mental training commonly applied in clinical settings and also practiced for general well-being. Brain functional connectivity (FC) patterns associated with meditation have revealed its brain mechanisms. However, the variety of FC methods applied has made it difficult to identify brain communication patterns associated with meditation. Here we carried out a coordinate-based meta-analysis to get preliminary evidence of meditation effects on changing brain network interactions. Fourteen seed-based, voxel-wise FC studies reported in 13 publications were reviewed; 10 studies with seeds in the default mode network (DMN) were meta-analyzed. Seed coordinates and the effect sizes in statistically significant regions were extracted, based on 170 subjects in meditation groups and 163 subjects in control groups. Seed-based d-mapping was used to analyze meditation versus control FC differences with DMN seeds. Meditation was associated with increased connectivity within DMN and between DMN and somatomotor network and with decreased connectivity between DMN and frontoparietal network (FPN) as well as ventral attention network (V

OBJECTIVE:To examine respiratory muscle function among late-onset Pompe disease (LOPD) patients in the Pompe Registry (NCT00231400/Sanofi Genzyme) during enzyme replacement therapy (ERT) with alglucosidase alfa by assessing the longitudinal course of forced vital capacity (FVC), prognostic factors for FVC, and impact of time from diagnosis to ERT initiation. METHODS:Longitudinal FVC data from LOPD (symptom onset > 12 months or ≤ 12 months without cardiomyopathy) patients were analyzed. Patients had to have baseline FVC (percent predicted upright) assessments at ERT start and ≥ 2 valid post-baseline assessments. Longitudinal analyses used linear mixed-regression models. RESULTS:Among 396 eligible patients, median baseline FVC was 66.9% (range 9.3-126.0). FVC remained stable during the 5-year follow-up (slope = - 0.17%, p = 0.21). Baseline FVC was lower among various subgroups, including patients who were male; older at ERT initiation; had a longer duration from symptom onset to ERT initiation; and had more advanced disease at baseline (based on respiratory support use, inability to ambulate, ambulation device use). Age at symptom onset was not associated with baseline degree of respiratory dysfunction. Differences between subgroups observed at baseline remained during follow-up. Shorter time from diagnosis to ERT initiation was associated with higher FVC after 5 years in all patients and the above subgroups using a cut-off of 1.7 years. CONCLUSION/CONCLUSIONS:FVC stability over 5 years suggests that respiratory function is preserved during long-term ERT in real-world settings. Early initiation of alglucosidase alfa was associated with preservation of FVC in LOPD patients with better respiratory function at the time of treatment initiation.

BACKGROUND:Advances in human neuroimaging has enabled us to study functional connections among various brain regions in pain states. Despite a wealth of studies at high anatomic resolution, the exact neural signals for the timing of pain remain little known. Identifying the onset of pain signals from distributed cortical circuits may reveal the temporal dynamics of pain responses and subsequently provide important feedback for closed-loop neuromodulation for pain. NEW METHOD/UNASSIGNED:Here we developed an unsupervised learning method for sequential detection of acute pain signals based on multichannel human EEG recordings. Following EEG source localization, we used a state-space model (SSM) to detect the onset of acute pain signals based on the localized regions of interest (ROIs). RESULTS:We validated the SSM-based detection strategy using two human EEG datasets, including one public EEG recordings of 50 subjects. We found that the detection accuracy varied across tested subjects and detection methods. We also demonstrated the feasibility for cross-subject and cross-modality prediction of detecting the acute pain signals. COMPARISON WITH EXISTING METHODS/UNASSIGNED:In contrast to the batch supervised learning analysis based on a support vector machine (SVM) classifier, the unsupervised learning method requires fewer number of training trials in the online experiment, and shows comparable or improved performance than the supervised method. CONCLUSIONS:Our unsupervised SSM-based method combined with EEG source localization showed robust performance in detecting the onset of acute pain signals.