Miracle-dz/UniFAR-FTUs huggingface dataset:
Predictors of Poor Outcome Despite Successful Mechanical Thrombectomy of Anterior Circulation Large Vessel Occlusions Within 6 h of Symptom Onset

Background and Purpose: Successful reperfusion is a significant predictor of a good clinical outcome after mechanical thrombectomy (MT). However, some patients have a poor clinical outcome even with successful reperfusion. We aimed to study factors that predict a poor clinical outcome (90-day modified Rankin Scale ≥ 3) in patients with anterior circulation large vessel occlusion (LVO) treated by successful MT within 6 h of symptom onset. Methods: We performed a retrospective review of a prospectively maintained MT database of all patients who underwent MT within 6 h of symptom onset for an anterior circulation LVO at our institution from May 2016 to June 2018. Uni- and multivariable analyses were performed to identify predictors of poor outcome. Results: A total of 56 patients met the criteria for inclusion in this study. A poor outcome occurred in 31 (55.4%) patients. On univariate analysis, compared to patients with good clinical outcome, patients with poor outcome had higher mean baseline NIHSS scores (23.3 vs. 13.8, P < 0.001), were more likely to have internal carotid artery (ICA) occlusions (38.7 vs. 8%, P = 0.008), and had a higher incidence of distal clot migration (DCM) (48.4 vs. 8%, P = 0.028). Age, gender, other baseline clinical characteristics, MT technique, and incidence of hemorrhagic transformation did not differ between the two cohorts. On multivariable regression analysis, baseline NIHSS score [OR; 1.3, 95%CI [1.11–1.52], P = 0.001], site of occlusion (ICA) [OR; 8.9, 95%CI [1.3–60.9], P = 0.026], and DCM [OR; 5.77, 95%CI [1.09–30.69], P = 0.04] were independent predictors of poor outcome at 90-days. Conclusion: Baseline NIHSS score, ICA occlusion, and DCM are independent predictors of a poor outcome after MT for anterior circulation LVO performed within 6 h of symptoms onset.
Comparative nest architecture of the dwarf honey bees

SUMMARYComplete descriptions using a variety of measurements are provided for nests of Apis andreniformis from south-eastern Thailand, Sichuan and Hunan Provinces of China, and Palawan, Philippines and Apis florea from southeastern Thailand and Hunan Province of China. Overall, the single-comb nest of A. andreniformis has a very different structure from that of A. florea. The comb built by A. andreniformis has a midrib both above and below the supporting branch. However, the comb built by A. florea has a mid-rib only in the brood area below the supporting branch. The honey storage mid-rib of A. andreniformis nests gives them a characteristic crown appearance. Other differences include the overall size of the nest, the width and depth of worker cells and the width of drone cells.
Sensorimotor Inhibition and Mobility in Genetic Subgroups of Parkinson's Disease

Background: Mobility and sensorimotor inhibition impairments are heterogeneous in Parkinson's disease (PD). Genetics may contribute to this heterogeneity since the apolipoprotein (APOE) ε4 allele and glucocerebrosidase (GBA) gene variants have been related to mobility impairments in otherwise healthy older adult (OA) and PD cohorts. The purpose of this study is to determine if APOE or GBA genetic status affects sensorimotor inhibition and whether the relationship between sensorimotor inhibition and mobility differs in genetic sub-groups of PD. Methods: Ninety-three participants with idiopathic PD (53 non-carriers; 23 ε4 carriers; 17 GBA variants) and 72 OA (45 non-carriers; 27 ε4 carriers) had sensorimotor inhibition characterized by short-latency afferent inhibition. Mobility was assessed in four gait domains (pace/turning, rhythm, trunk, variability) and two postural sway domains (area/jerkiness and velocity) using inertial sensors. Results: Sensorimotor inhibition was worse in the PD than OA group, with no effect of genetic status. Gait pace/turning was slower and variability was higher (p < 0.01) in PD compared to OA. Postural sway area/jerkiness (p < 0.01) and velocity (p < 0.01) were also worse in the PD than OA group. Genetic status was not significantly related to any gait or postural sway domain. Sensorimotor inhibition was significantly correlated with gait variability (r = 0.27; p = 0.02) and trunk movement (r = 0.23; p = 0.045) in the PD group. In PD non-carriers, sensorimotor inhibition related to variability (r = 0.35; p = 0.010) and trunk movement (r = 0.31; p = 0.025). In the PD ε4 group, sensorimotor inhibition only related to rhythm (r = 0.47; p = 0.024), while sensorimotor inhibition related to pace/turning (r = −0.49; p = 0.046) and rhythm (r = 0.59; p = 0.013) in the PD GBA group. Sensorimotor inhibition was significantly correlated with gait pace/turning (r = −0.27; p = 0.04) in the OA group. There was no relationship between sensorimotor inhibition and postural sway. Conclusion: ε4 and GBA genetic status did not affect sensorimotor inhibition or mobility impairments in this PD cohort. However, worse sensorimotor inhibition was associated with gait variability in PD non-carriers, but with gait rhythm in PD ε4 carriers and with gait rhythm and pace in PD with GBA variants. Impaired sensorimotor inhibition had a larger effect on mobility in people with PD than OA and affected different domains of mobility depending on genetic status.
The selected lymphocyte antibody method : a novel approach for the generation and genetic analysis of human cytomegalovirus (HCMV) neutralizing monoclonal IgG antibodies

The generation of human monoclonal antibodies that may be clinically useful is hampered by the lack of an efficient, applicable technology. In this thesis I report the development of the Selected Lymphocyte Antibody Method (SLAM) as an alternative approach to generate monoclonal antibodies and to facilitate the analysis of the human humoral immune response. SLAM technology is based upon the molecular cloning and expression of immunoglobulin heavy and light chain variable region cDNAs from single B lymphocytes that have been identified in a modified hemolytic plaque assay as secreting immunoglobulin which is specific for a target antigen. SLAM technology was first developed in a murine model. Immunoglobulin variable region cDNAs were RT-PCR amplified from single murine B lymphocytes that secreted immunoglobulin which is specific for an epitope found in gpll6 of the Human Cytomegalovirus (HCMV) or in gpl20 of HIV-1. These immunoglobulin variable regions were then cloned and expressed in the context of human immunoglobulin constant regions. The resulting chimeric immunoglobulins were shown to reproduce the same specificity as the "parental" immunoglobulin. To generate human monoclonal antibodies that were specific for gpl 16, peripheral blood B lymphocytes from a single HCMV immune donor were cultured at limiting dilution in the "EL4.B5" B-cell culture system. 107 single B lymphocytes, corrresponding to 34 clones that secreted gpll6-specific immunoglobulin, were identified by hemolytic plaque assay and then isolated by micromanipulation. Immunoglobulin variable region cDNAs were successfully RT-PCR amplified from 29 of the 34 clones. Sequence analysis of the V region cDNAs showed a remarkable restriction in the use of heavy chain variable and joining gene segments as well as restriction in the use of kappa light chain variable and joining gene segments in the associated light chains. Two independent B cell clonotypes were identified based on the utilization of different diversity gene segments in the heavy chain variable regions. Two recombinant monoclonal antibodies (mAbs) that represent each clonotype were expressed and were shown to neutralize HCMV in vitro. Thus, SLAM technology facilitated the generation of two potentially clinically useful antibodies and may be used in the future to generate mAbs against a wide variety of pathogens.
Vespertilioninae systematics: Using mitochondrial and nuclear markers to elucidate phylogenetic relationships

A paucity of useful characters, morphological convergence, and potential rapid radiation has hindered systematists in elucidating evolutionary relationships within Vespertilioninae. In this study >8,500 base pairs of digenomic DNA for 113 taxa were sequenced and analyzed using maximum parsimony and Bayesian phylogenetic procedures to construct gene trees and test hypotheses of supergeneric evolutionary relationships in Vespertilioninae. Results of these analyses validate monophyly of Vespertilioninae with the exclusion of Myotis and support recognition of 6 tribes: Antrozoini, Lasiurini, Scotophilini, Vespertilionini, and 2 new unnamed tribal clades, the Perimyotine group and the Hypsugine group. Tree topologies indicate a Nycticeiini / Eptesicini group, but it is not supported. The heuristically pleasing tribe Plecotini also is unresolved in these gene trees. These results provided further support and greater resolution for previously proposed hypotheses of Vespertilioninae evolution based on mtDNA and, although deep branching patterns are not fully resolved, these data increase our understanding of the evolution of this ecologically important and diverse group of
Pulsed Electric Fields-Assisted Extraction of Valuable Compounds From Arthrospira Platensis: Effect of Pulse Polarity and Mild Heating

The present study aimed to investigate the effect of the main pulsed electric field (PEF) process parameters on the cell damages of A. platensis microalgae and the extractability of valuable compounds [water-soluble proteins (WSP), C-phycocyanin (C-PC), and carbohydrates (CH)]. Aqueous microalgae suspensions (2%, w/w) were PEF-treated at variable field strength (E = 10, 20, 30 kV/cm), total specific energy (WT = 20, 60, 100 kJ/kgsusp), and inlet temperature (25, 35, 45°C), with either monopolar or bipolar square wave pulses (5 μs of width, delay time between pulses of opposite polarities = 1, 5, 10, 20 μs), prior to extraction with water at room temperature (25°C) for up to 3 h. High-pressure homogenization (HPH) treatment (P = 150 MPa, 3 passes) was used to achieve complete cell disruption to quantify the total extractable content of target intracellular compounds. Scanning electron microscopy (SEM) and optical microscopy analyses clearly showed that PEF merely electroporated the membranes of algae cell, without damaging the cell structure and forming cell debris. The application of PEF treatment (monopolar pulses, 20 kV/cm and 100 kJ/kgsusp) at room temperature significantly enhanced the extraction yield of WSP [17.4% dry weight (DW)], CH (10.1% DW), and C-PC (2.1% DW), in comparison with the untreated samples. Bipolar pulses appeared less effective than monopolar pulses and led to extraction yields dependent on the delay time. Additionally, regardless of pulse polarity, a clear synergistic effect of the combined PEF (20 kV/cm and 100 kJ/kgsusp)-temperature (35°C) treatment was detected, which enabled the extraction of up to 37.4% (w/w) of total WSP, 73.8% of total CH, and 73.7% of total C-PC. Remarkably, the PEF treatment enabled to obtain C-phycocyanin extract with higher purity than that obtained using HPH treatment. The results obtained in this work suggest that the application of PEF combined with mild heating could represent a suitable approach for the efficient recovery of water-soluble compounds microalgal biomass.
Haplotype Block Analysis Reveals Candidate Genes and QTLs for Meat Quality and Disease Resistance in Chinese Jiangquhai Pig Breed

The Jiangquhai (JQ) pig breed is one of the most widely recognized pig populations in China due to its unique and dominant characteristics. In this study, we examined the extent of Linkage disequilibrium (LD) and haplotype block structure of the JQ pig breed, and scanned the blocks for possible genes underlying important QTLs that could either be responsible for some adaptive features in these pigs or might have undergone some selection pressure. We compared some of our results with other Chinese and Western pig breeds. The results show that the JQ breed had the highest total block length (349.73 Mb ≈ 15% of its genome), and the coverage rate of blocks in most of its chromosomes was larger than those of other breeds except for Sus scrofa chromosome 4 (SSC4), SSC6, SSC7, SSC8, SSC10, SSC12, SSC13, SSC14, SSC17, SSC18, and SSCX. Moreover, the JQ breed had more SNPs that were clustered into haplotype blocks than the other breeds examined in this study. Our shared and unique haplotype block analysis revealed that the Hongdenglong (HD) breed had the lowest percentage of shared haplotype blocks while the Shanzhu (SZ) breed had the highest. We found that the JQ breed had an average r2 > 0.2 at SNPs distances 10–20 kb and concluded that about 120,000–240,000 SNPs would be needed for a successful GWAS in the breed. Finally, we detected a total of 88 genes harbored by selected haplotype blocks in the JQ breed, of which only 4 were significantly enriched (p-value ≤ 0.05). These genes were significantly enriched in 2 GO terms (p-value < 0.01), and 2 KEGG pathways (p-value < 0.02). Most of these enriched genes were related to health. Also, most of the overlapping QTLs detected in the haplotype blocks were related to meat and carcass quality, as well as health, with a few of them relating to reproduction and production. These results provide insights into the genetic architecture of some adaptive and meat quality traits observed in the JQ pig breed and also revealed the pattern of LD in the genome of the pig. Our result provides significant guidance for improving the statistical power of GWAS and optimizing the conservation strategy for this JQ pig breed.
HMGB1 Promotes Myeloid Egress and Limits Lymphatic Clearance of Malignant Pleural Effusions

Pleural effusions, when benign, are attributed to cardiac events and suffusion of fluid within the pleural space. When malignant, lymphatic obstruction by tumor and failure to absorb constitutively produced fluid is the predominant formulation. The prevailing view has been challenged recently, namely that the lymphatics are only passive vessels, carrying antigenic fluid to secondary lymphoid sites. Rather, lymphatic vessels can be a selective barrier, efficiently coordinating egress of immune cells and factors within tissues, limiting tumor spread and immune pathology. An alternative explanation, offered here, is that damage associated molecular pattern molecules, released in excess, maintain a local milieu associated with recruitment and retention of immune cells associated with failed lymphatic clearance and functional lymphatic obstruction. We found that levels of high mobility group box 1 (HMGB1) were equally elevated in both benign and malignant pleural effusions (MPEs) and that limited diversity of T cell receptor expressing gamma and delta chain were inversely associated with these levels in MPEs. Acellular fluid from MPEs enhanced γδ T cell proliferation in vitro, while inhibiting cytokine production from γδ T cells and monocytes as well as restricting monocyte chemotaxis. Novel therapeutic strategies, targeting HMGB1 and its neutralization in such effusions as well as direct delivery of immune cells into the pleural space to reconstitute normal physiology should be considered.
Brain Processes While Struggling With Evidence Accumulation During Facial Emotion Recognition: An ERP Study

The human brain is tuned to recognize emotional facial expressions in faces having a natural upright orientation. The relative contributions of featural, configural, and holistic processing to decision-making are as yet poorly understood. This study used a diffusion decision model (DDM) of decision-making to investigate the contribution of early face-sensitive processes to emotion recognition from physiognomic features (the eyes, nose, and mouth) by determining how experimental conditions tapping those processes affect early face-sensitive neuroelectric reflections (P100, N170, and P250) of processes determining evidence accumulation at the behavioral level. We first examined the effects of both stimulus orientation (upright vs. inverted) and stimulus type (photographs vs. sketches) on behavior and neuroelectric components (amplitude and latency). Then, we explored the sources of variance common to the experimental effects on event-related potentials (ERPs) and the DDM parameters. Several results suggest that the N170 indicates core visual processing for emotion recognition decision-making: (a) the additive effect of stimulus inversion and impoverishment on N170 latency; and (b) multivariate analysis suggesting that N170 neuroelectric activity must be increased to counteract the detrimental effects of face inversion on drift rate and of stimulus impoverishment on the stimulus encoding component of non-decision times. Overall, our results show that emotion recognition is still possible even with degraded stimulation, but at a neurocognitive cost, reflecting the extent to which our brain struggles to accumulate sensory evidence of a given emotion. Accordingly, we theorize that: (a) the P100 neural generator would provide a holistic frame of reference to the face percept through categorical encoding; (b) the N170 neural generator would maintain the structural cohesiveness of the subtle configural variations in facial expressions across our experimental manipulations through coordinate encoding of the facial features; and (c) building on the previous configural processing, the neurons generating the P250 would be responsible for a normalization process adapting to the facial features to match the stimulus to internal representations of emotional expressions.
A Novel Kv7.3 Variant in the Voltage-Sensing S4 Segment in a Family With Benign Neonatal Epilepsy: Functional Characterization and in vitro Rescue by β-Hydroxybutyrate

Pathogenic variants in KCNQ2 and KCNQ3, paralogous genes encoding Kv7.2 and Kv7.3 voltage-gated K+ channel subunits, are responsible for early−onset developmental/epileptic disorders characterized by heterogeneous clinical phenotypes ranging from benign familial neonatal epilepsy (BFNE) to early−onset developmental and epileptic encephalopathy (DEE). KCNQ2 variants account for the majority of pedigrees with BFNE and KCNQ3 variants are responsible for a much smaller subgroup, but the reasons for this imbalance remain unclear. Analysis of additional pedigrees is needed to further clarify the nature of this genetic heterogeneity and to improve prediction of pathogenicity for novel variants. We identified a BFNE family with two siblings and a parent affected. Exome sequencing on samples from both parents and siblings revealed a novel KCNQ3 variant (c.719T>G; p.M240R), segregating in the three affected individuals. The M240 residue is conserved among human Kv7.2-5 and lies between the two arginines (R5 and R6) closest to the intracellular side of the voltage-sensing S4 transmembrane segment. Whole cell patch-clamp recordings in Chinese hamster ovary (CHO) cells revealed that homomeric Kv7.3 M240R channels were not functional, whereas heteromeric channels incorporating Kv7.3 M240R mutant subunits with Kv7.2 and Kv7.3 displayed a depolarizing shift of about 10 mV in activation gating. Molecular modeling results suggested that the M240R substitution preferentially stabilized the resting state and possibly destabilized the activated state of the Kv7.3 subunits, a result consistent with functional data. Exposure to β-hydroxybutyrate (BHB), a ketone body generated during the ketogenic diet (KD), reversed channel dysfunction induced by the M240R variant. In conclusion, we describe the first missense loss-of-function (LoF) pathogenic variant within the S4 segment of Kv7.3 identified in patients with BFNE. Studied under conditions mimicking heterozygosity, the M240R variant mainly affects the voltage sensitivity, in contrast to previously analyzed BFNE Kv7.3 variants that reduce current density. Our pharmacological results provide a rationale for the use of KD in patients carrying LoF variants in Kv7.2 or Kv7.3 subunits.
Two Coarse Spatial Patterns of Altered Brain Microstructure Predict Post-traumatic Amnesia in the Subacute Stage of Severe Traumatic Brain Injury

Introduction: Diffuse traumatic axonal injury (TAI) is one of the key mechanisms leading to impaired consciousness after severe traumatic brain injury (TBI). In addition, preferential regional expression of TAI in the brain may also influence clinical outcome. Aim: We addressed the question whether the regional expression of microstructural changes as revealed by whole-brain diffusion tensor imaging (DTI) in the subacute stage after severe TBI may predict the duration of post-traumatic amnesia (PTA). Method: Fourteen patients underwent whole-brain DTI in the subacute stage after severe TBI. Mean fractional anisotropy (FA) and mean diffusivity (MD) were calculated for five bilateral brain regions: fronto-temporal, parieto-occipital, and midsagittal hemispheric white matter, as well as brainstem and basal ganglia. Region-specific calculation of mean FA and MD only considered voxels that showed no tissue damage, using an exclusive mask with all voxels that belonged to local brain lesions or microbleeds. Mean FA or MD of the five brain regions were entered in separate partial least squares (PLS) regression analyses to identify patterns of regional microstructural changes that account for inter-individual variations in PTA. Results: For FA, PLS analysis revealed two spatial patterns that significantly correlated with individual PTA. The lower the mean FA values in all five brain regions, the longer that PTA lasted. A pattern characterized by lower FA values in the deeper brain regions relative to the FA values in the hemispheric regions also correlated with longer PTA. Similar trends were found for MD, but opposite in sign. The spatial FA changes as revealed by PLS components predicted the duration of PTA. Individual PTA duration, as predicted by a leave-one-out cross-validation analysis, correlated with true PTA values (Spearman r = 0.68, ppermutation = 0.008). Conclusion: Two coarse spatial patterns of microstructural damage, indexed as reduction in FA, were relevant to recovery of consciousness after TBI. One pattern expressed was consistent with diffuse microstructural damage across the entire brain. A second pattern was indicative of a preferential damage of deep midline brain structures.