Miracle-dz/UniFAR-FTUs huggingface dataset:
Statistical Analysis of fNIRS Data: Consideration of Spatial Varying Coefficient Model of Prefrontal Cortex Activity Changes During Speech Motor Learning in Apraxia of Speech

Apraxia of speech is an impairment in the planning and programming of speech typically accompanied by aphasia (language impairment) secondary to a left hemisphere stroke. It is unknown if the structural and functional connections to the damaged area implicate the integrity of the cognitive functions of the prefrontal cortex (PFC). The present study examines the feasibility of measuring hemodynamic activity in the PFC in response to the structure of practice and during treatment. This multiple-baseline single case-design study involving two individuals with chronic acquired apraxia of speech measured the hemodynamic changes in PFC activity during treatment across the intervention period using functional near-infrared spectroscopy (fNIRS). Two models—a generalized linear model and a spatial varying coefficient model—are used to distinguish the repeated measures of PFC activity differences corresponding to the stage of practice and time of intervention. There were significant differences in the pattern of PFC activity associated with the structure of practice and the time of intervention. The outcomes from this pilot study demonstrate the utility of fNIRS to identify cognitive effort during speech motor learning. The implications include consideration for statistical methods used for fNIRS analysis and its potential use as a clinical tool to complement behavior changes to guide patient-directed intervention to optimize patient outcomes.
Circulating miRNAs Associated With ER Stress and Organ Damage in a Preclinical Model of Trauma Hemorrhagic Shock

Circulating microRNAs (miRNA) alterations have been reported in severe trauma patients but the pathophysiological relevance of these changes is still unclear. miRNAs are critical biologic regulators of pathological events such as hypoxia and inflammation, which are known to induce endoplasmic reticulum (ER) stress. ER stress is emerging as an important process contributing to the development of single and/or multiple organ dysfunction after trauma hemorrhagic shock (THS) accompanied by impaired tissue microcirculation and inflammation. Here, we aim to bring new insights into the involvement of miRNAs associated with ER stress in THS. THS was induced in rats by a median laparotomy and blood withdrawal until mean arterial pressure (MAP) dropped to 30-35 mmHg followed by a restrictive (40 min) and full reperfusion (60 min) with Ringer's solution. Tunicamycin was used to induce ER stress. Blood samples were collected 24 h after THS for the determination of pathological changes in the blood (PCB) and circulating miRNAs. Plasma levels of circulating miRNAs were compared between THS, tunicamycin, and sham groups and correlated to biomarkers of PCB. MiRNA profile of THS animals showed that 40 out of 91 (44%) miRNAs were significantly upregulated compared to sham (p < 0.01). The data showed a very strong correlation between liver injury and miR−122-5p (r = 0.91, p < 0.00001). MiR-638, miR−135a-5p, miR−135b-5p, miR-668-3p, miR-204-5p, miR−146a-5p, miR−200a-3p, miR−17-5p, miR−30a-5p, and miR−214-3p were found positively correlated with lactate (r > 0.7, p < 0.05), and negatively with base excess (r ≤ 0.8, p < 0.05) and bicarbonate (r ≤ 0.8, p < 0.05), which are clinical parameters that reflected the shock severity. Tunicamycin significantly modified the microRNA profile of the animals, 33 out of 91 miRNAs were found differentially expressed. In addition, principal component analysis revealed that THS and tunicamycin induced similar changes in plasma miRNA patterns. Strikingly, the data showed that 15 (25.9%) miRNAs were regulated by both THS and tunicamycin (p < 0.01). This included miR−122-5p, a liver-specific microRNA, but also miR−17-5p and miR-125b-5p which are miRNAs remarkably involved in unfolded protein response (UPR)-mediating pro-survival signaling (IRE1α). Since miRNAs associated with ER stress are clearly correlated with THS, our data strongly suggest that interaction between miRNAs and ER stress is an important pathologic event occurring during THS. Overall, we consider that the miRNA profile developed in this study can provide a rationale for the development of bench-to-bedside strategies that target miRNAs in critical care diseases or be used as biomarkers in the prognosis of trauma patients.
Glioma Cells With Genetically Engineered IGF-I Receptor Downregulation Can Persist in the Brain in a Dormant State

Glioblastoma multiforme is an aggressive malignancy, resistant to standard treatment modalities and associated with poor prognosis. We analyzed the role of the IGF system in intracerebral glioma growth using human and rat glioma cells. The glioma cells C6 and U87MG were transduced with a genetically engineered retrovirus expressing type 1 insulin-like growth factor (IGF-IR) antisense RNA, either before or after intra-cerebral implantation of the cells into Sprague Dawley rats or nude mice, respectively and tumor growth and animal survival were monitored. Rat glioma cells transduced prior to orthotopic, intra-cerebral implantation had a significantly increased apoptotic rate in vivo and a significantly reduced tumor volume as seen 24 days post implantation (p < 0.0015). This resulted in increased survival, as greater than 70% of the rats were still alive 182 days after tumor implantation (p < 0.01), as compared to 80% mortality by day 24 in the control group. Histomorphology and histochemical studies performed on brain tissue that was obtained from rats that survived for 182 days revealed numerous single cells that were widely disseminated throughout the brain. These cells expressed the β-galactosidase marker protein, but were Ki67negative, suggesting that they acquired a dormant phenotype. Direct targeting of the C6 cells with retroviral particles in vivo was effective and reduced tumor volumes by 22% relative to controls. A significant effect on tumor growth was also seen with human glioma U87MG cells that were virally transduced and implanted intra-cerebrally in nude mice. We observed in these mice a significant reduction in tumor volumes and 70% of the animals were still alive 6 months after tumor implantation, as compared to 100% mortality in the control group by day 63. Our results show that IGF-IR targeting can inhibit the intracerebral growth of glioma cells. They also suggest that IGF-IR expression levels may determine a delicate balance between glioma cell growth, death and the acquisition of a dormant state in the brain.
Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) Regulates Neurite Outgrowth Through the Activation of Akt/mTOR and Erk/mTOR Signaling Pathways

Neurite outgrowth is essential for brain development and the recovery of brain injury and neurodegenerative diseases. In this study, we examined the role of the neurotrophic factor MANF in regulating neurite outgrowth. We generated MANF knockout (KO) neuro2a (N2a) cell lines using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 and demonstrated that MANF KO N2a cells failed to grow neurites in response to RA stimulation. Using MANF siRNA, this finding was confirmed in human SH-SY5Y neuronal cell line. Nevertheless, MANF overexpression by adenovirus transduction or addition of MANF into culture media facilitated the growth of longer neurites in RA-treated N2a cells. MANF deficiency resulted in inhibition of Akt, Erk, mTOR, and P70S6, and impaired protein synthesis. MANF overexpression on the other hand facilitated the growth of longer neurites by activating Akt, Erk, mTOR, and P70S6. Pharmacological blockade of Akt, Erk or mTOR eliminated the promoting effect of MANF on neurite outgrowth. These findings suggest that MANF positively regulated neurite outgrowth by activating Akt/mTOR and Erk/mTOR signaling pathways.
Reconsidering the Active Psychological Ingredients Underlying Intercultural Adaptation: Implications for International Business

A major issue facing many businesses today, both large and small, concerns intercultural adaptation, and more broadly, diversity. Many businesses struggle with their employees sent to different countries and cultures to adapt effectively in host cultures, as well as for their home culture employees to adapt effectively to changing environments brought on by visitors from other cultures and other sources of diversity. To address this issue, many tests and measures have been developed to identify the core psychological skills, competencies, and aptitudes underlying intercultural adaptation. Elucidation of such skills and competencies would have multiple theoretical and practical ramifications. A recent review of this literature indicated that three tests – the Multicultural Personality Questionnaire, the Cultural Intelligence Scale, and the Intercultural Adjustment Potential Scale – had the best psychometric evidence for validity to date. No study, however, has examined the statistical overlap among these tests; which scales or combination of scales best predict adaptation; and most importantly, what are possible, yet unassessed, constructs underlying them. The purpose of this study was to examine these three questions initially. Non-immigrant, non-sojourner convenience samples from four countries/language groups completed all three tests and a measure of life satisfaction as a proxy for adaptation. Scales from the three tests were moderately – highly intercorrelated and predicted adaptation. A combination of scales from the tests best predicted adaptation, better than scales from any one test. Analyses examining the latent structures underlying the combined tests suggested several psychological constructs new to the intercultural adaptation literature. We discuss the implications of these findings for theory and application in international business.
A Review of Recent Solar Type III Imaging Spectroscopy

Solar type III radio bursts are the most common impulsive radio signatures from the Sun, stimulated by electron beams traveling through the solar corona and solar wind. Type III burst analysis provides us with a powerful remote sensing diagnostic tool for both the electron beams and the plasma they travel through. Advanced radio telescopes like the LOw Frequency ARray (LOFAR), the Murchison Widefield Array (MWA) and the Karl G. Jansky Very Large Array (VLA) are now giving us type III imaging spectroscopy with orders of magnitude better resolution than before. In this review, the recent observational progress provided by the new observations is discussed for type III bursts at GHz and MHz frequencies, including how this enhanced resolution has facilitated study of type III burst fine structure. The new results require more detailed theoretical understanding of how type III bursts are produced. Consequently, recent numerical work is discussed which improves our understanding of how electron beams, Langmuir waves and radio waves evolve through the turbulent solar system plasma. Looking toward the future, some theoretical challenges are discussed that we need to overcome on our quest to understand type III bursts and the electron beams that drive them.
Role of BgaA as a Pneumococcal Virulence Factor Elucidated by Molecular Evolutionary Analysis

Streptococcus pneumoniae is a major cause of pneumonia, sepsis, and meningitis. Previously, we identified a novel virulence factor by investigating evolutionary selective pressure exerted on pneumococcal choline-binding cell surface proteins. Herein, we focus on another pneumococcal cell surface protein. Cell wall-anchoring proteins containing the LPXTG motif are conserved in Gram-positive bacteria. Our evolutionary analysis showed that among the examined genes, nanA and bgaA had high proportions of codon that were under significant negative selection. Both nanA and bgaA encode a multi-functional glycosidase that aids nutrient acquisition in a glucose-poor environment, pneumococcal adherence to host cells, and evasion from host immunity. However, several studies have shown that the role of BgaA is limited in a mouse pneumonia model, and it remains unclear if BgaA affects pneumococcal pathogenesis in a mouse sepsis model. To evaluate the distribution and pathogenicity of bgaA, we performed phylogenetic analysis and intravenous infection assay. In both Bayesian and maximum likelihood phylogenetic trees, the genetic distances between pneumococcal bgaA was small, and the cluster of pneumococcal bgaA did not contain other bacterial orthologs except for a Streptococcus gwangjuense gene. Evolutionary analysis and BgaA structure indicated BgaA active site was not allowed to change. The mouse infection assay showed that the deletion of bgaA significantly reduced host mortality. These results indicated that both nanA and bgaA encode evolutionally conserved pneumococcal virulence factors and that molecular evolutionary analysis could be a useful alternative strategy for identification of virulence factors.
Effects of Possible Osteoporotic Conditions on the Recurrence of Chronic Subdural Hematoma

The recurrence rate of chronic subdural hematoma (CSDH) has been reported to range from 2.3 to 33%. As bridging veins are composed of abundant collagen bundles and bone matrix, we aimed to investigate the possible associations between skull Hounsfield unit (HU) values and the recurrence of CSDH. We retrospectively enrolled patients with CSDH who underwent burr hole surgery. The HU values of the frontal skull were measured on brain CT scans. The cumulative hazard for recurrence was estimated according to predictive factors. To identify the independent predictors associated with the recurrence of CSDH, hazard ratios (HRs) were estimated using multivariate Cox regression analysis. A total of 208 consecutive patients who underwent burr hole trephination for CSDH over a 7-years period at a single institution were enrolled in this study. We found that age, greater midline shift (≥10.5 mm), lower skull HU (<769.5), and diabetes were independent predictors for the recurrence of CSDH (HR 1.06, 95% confidence interval [CI] 1.00–1.12, p = 0.042; HR 5.37, 95% CI 1.48–19.46, p = 0.010; HR 6.71, 95% CI 1.84–24.45, p = 0.004; and HR 3.30, 95% CI 1.05–10.43, p = 0.042, respectively). A relationship between possible low bone mineral density (BMD) and CSDH recurrence was observed. In addition, age, greater preoperative midline shift, and diabetes were also identified as predictive factors for recurrence. We expect that our findings may facilitate our understanding of the possible association between CSDH and BMD.
Microbiota and Lung Cancer. Opportunities and Challenges for Improving Immunotherapy Efficacy

The advances in molecular biology and the emergence of Next Generation Sequencing (NGS) have revealed that microbiome composition is closely related with health and disease, including cancer. This relationship affects different levels of cancer such as development, progression, and response to treatment including immunotherapy. The efficacy of immune checkpoint inhibitors (ICIs) may be influenced by the concomitant use of antibiotics before, during or shortly after treatment with ICIs. Nevertheless, the linking mechanism between microbiote, host immunity and cancer is not clear and the role of microbiota manipulation and analyses in cancer management has not been clinically validated yet. Regarding the use of microbiome as biomarker to predict ICI efficacy it has been recently shown that the use of biochemical serum markers to monitor intestinal permeability and loss of barrier integrity, like citrulline, could be useful to monitor microbiota changes and predict ICI efficacy. There are still many unknowns about the role of these components, their relationship with the microbiota, with the use of antibiotics and the response to immunotherapy. The next challenge in microbiome research will be to identify individual microbial species that causally affect lung cancer phenotypes and response to ICI and disentangle the underlying mechanisms. Thus, further analyses in patients with lung cancer receiving treatment with ICIs and its correlation with the composition of the microbiota in different organs including the respiratory tract, peripheral blood and intestinal tract could be useful to predict the efficacy of ICIs and its modulation with antibiotic use.
Supporting Fisheries Management With Genomic Tools: A Case Study of Kingklip (Genypterus capensis) Off Southern Africa

Kingklip, Genypterus capensis, is a valuable fish resource in southern African waters, with a wide geographic distribution spanning South Africa and Namibia. Previous studies have provided evidence for multiple stocks in South Africa, but the extent of stock structuring across the southern Africa region remains unclear. In this study we genotyped over 40,000 SNPs to characterize the spatial distribution of genomic variation for G. capensis throughout its core distribution. Results suggest that fish sampled at the northernmost range (off central Namibia) are characterized by lower genomic diversity, although the region exhibited the highest number of private SNPs, suggesting some degree of geographic isolation. Using neutral and putative outlier loci independently, we show that kingklip exhibits three population clusters, “northern Benguela,” “southern Benguela,” and South African “South Coast. ” Population differentiation was observed only using putative outlier loci, suggesting that local adaptation might be one of the main drivers of the observed differentiation. Overall, our research provides novel insights into the regional dynamics that can support the sustainable long-term exploitation of this valuable fisheries resource.
Hemophagocytic Lymphohistiocytosis During HIV Infection in Cayenne Hospital 2012–2015: First Think Histoplasmosis

Introduction: Haemophagocytic Lymphohistiocytosis (HLH), during HIV infection is a rare complication with a poor prognosis. There are few data on HLH within the Amazon region. The objective was to describe epidemiological, clinical and therapeutic features of HIV-related HLH in French Guiana. Methods: A retrospective analysis of adult HIV patients at Cayenne hospital with HLH between 2012 and 2015. A diagnosis of HLH was given if the patient presented at least 3 of 8 criteria of the HLH-2004 classification. Results: Fourteen cases of HLH were tallied during the study period. The mean age was 46 years with a sex ratio of 1.8. The most frequent etiology of HLH was an associated infection (12/14). Confirmed disseminated histoplasmosis, was found in 10 of 14 cases, and it was suspected in 2 other cases. The CD4 count was below 200/mm3 in 13/14 cases. An HIV viral load >100,000 copies/ml was observed in 13/14 cases. An early treatment with liposomal amphotericin B was initiated in 12/14 cases. The outcome was favorable in 12/14 of all cases and in 10/12 cases involving histoplasmosis. Case fatality was 2/14 among all cases (14.3%) et 1/10 among confirmed disseminated histoplasmosis with HLH (10%). During the study period 1 in 5 cases of known HIV-associated disseminated histoplasmosis in French Guiana was HLH. Conclusion: Histoplasmosis was the most frequent etiology associated with HLH in HIV-infected patients in French Guiana. The prognosis of HLH remains severe. However, a probabilistic empirical first line treatment with liposomal amphotericin B seemed to have a favorable impact on patient survival.
Neutrophil: A New Player in Metastatic Cancers

The interaction between cancer cells and immune cells is important for the cancer development. However, much attention has been given to T cells and macrophages. Being the most abundant leukocytes in the blood, the functions of neutrophils in cancer have been underdetermined. They have long been considered an “audience” in the development of cancer. However, emerging evidence indicate that neutrophils are a heterogeneous population with plasticity, and subpopulation of neutrophils (such as low density neutrophils, polymorphonuclear-myeloid-derived suppressor cells) are actively involved in cancer growth and metastasis. Here, we review the current understanding of the role of neutrophils in cancer development, with a specific focus on their pro-metastatic functions. We also discuss the potential and challenges of neutrophils as therapeutic targets. A better understanding the role of neutrophils in cancer will discover new mechanisms of metastasis and develop new immunotherapies by targeting neutrophils.
Aberrant White Matter Microstructure as a Potential Diagnostic Marker in Alzheimer's Disease by Automated Fiber Quantification

Neuroimaging evidence has suggested white matter microstructure are heavily affected in Alzheimer's disease (AD). However, whether white matter dysfunction is localized at the specific regions of fiber tracts and whether they would be a potential biomarker for AD remain unclear. By automated fiber quantification (AFQ), we applied diffusion tensor images from 25 healthy controls (HC), 24 amnestic mild cognitive impairment (aMCI) patients and 18 AD patients to create tract profiles along 16 major white matter fibers. We compared diffusion metrics [Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (DA), and radial diffusivity (DR)] between groups. To assess the diagnostic value, we applied a random forest (RF) classifier, a type of machine learning method. In the global tract level, we found that aMCI and AD patients showed higher MD, DA, and DR values in some fiber tracts mostly in the left hemisphere compared to HC. In the point-wise level, widespread disruption were distributed on specific locations of different tracts. The point-wise MD measurements presented the best classification performance with respect to differentiating AD from HC. The two most important variables were localized in the prefrontal potion of left uncinate fasciculus and anterior thalamic radiation. In addition, the point-wise DA in the posterior component of the left cingulum cingulate displayed the most robust discriminative ability to identify AD from aMCI. Our findings provide evidence that white matter abnormalities based on the AFQ method could be as a diagnostic biomarker in AD.
Long Non-coding RNA GAS5 Maintains Insulin Secretion by Regulating Multiple miRNAs in INS-1 832/13 Cells

Type-2 diabetes mellitus (T2DM) is a complex disease characterized by reduced pancreatic islets β-cell mass and impaired insulin release from these cells. Non-coding RNAs, including microRNAs (miRNA) and long non-coding RNAs (lncRNAs), play a role in the progression of T2DM. Decreased serum lncRNA GAS5 levels were reported to be associated with T2DM. However, the role of GAS5 in regulating islet cell functions remain unknown. In this study, we found that the serum levels of GAS5 were significantly lower in patients with T2DM compared with healthy control subjects, and the low serum GAS5 levels were associated with high levels of HbAlc and fasting glucose in patients with T2DM. In addition, we found that serum GAS5 levels were negatively correlated with the serum levels of miR-29a-3p, miR-96-3p, and miR-208a-3p in patients with T2DM. Consequently, using INS-1 832/13 rat β-cell line, we found that overexpression of GAS5 by lentivirus infection increased glucose-stimulated insulin secretion and insulin content compared with negative control, whereas knockdown of GAS5 expression reduced both them. Moreover, GAS5 interacted with miR-29a-3p, miR-96-3p, and miR-208a-3p in INS-1 832/13 cells, as judged by pull-down assay and dual luciferase reporter assay. GAS5 overexpression caused the decrease in expression of miR-29a-3p, miR-96-3p, and miR-208a-3p in INS-1 832/13 cells and conversely caused the increase in expression of insulin receptor, insulin receptor substrate, and phosphoinositide-3-kinase regulatory subunit 1. Thus, these results reveal a novel mechanism whereby GAS5 is involved in maintaining insulin secretion and may represent a novel therapeutic target for T2DM.