Miracle-dz/UniFAR-FTUs huggingface dataset:
Laser Adjuvant-Assisted Peptide Vaccine Promotes Skin Mobilization of Dendritic Cells and Enhances Protective CD8+ TEM and TRM Cell Responses against Herpesvirus Infection and Disease

ABSTRACT There is an urgent need for chemical-free and biological-free safe adjuvants to enhance the immunogenicity of vaccines against widespread viral pathogens, such as herpes simplex virus 2 (HSV-2), that infect a large proportion of the world human population. In the present study, we investigated the safety, immunogenicity, and protective efficacy of a laser adjuvant-assisted peptide (LAP) vaccine in the B6 mouse model of genital herpes. This LAP vaccine and its laser-free peptide (LFP) vaccine analog contain the immunodominant HSV-2 glycoprotein B CD8+ T cell epitope (HSV-gB498–505) covalently linked with the promiscuous glycoprotein D CD4+ T helper cell epitope (HSV-gD49–89). Prior to intradermal delivery of the LAP vaccine, the lower-flank shaved skin of B6 or CD11c/eYFP transgenic mice received a topical skin treatment with 5% imiquimod cream and then was exposed for 60 s to a laser, using the FDA-approved nonablative diode. Compared to the LFP vaccine, the LAP vaccine (i) triggered mobilization of dendritic cells (DCs) in the skin, which formed small spots along the laser-treated areas, (ii) induced phenotypic and functional maturation of DCs, (iii) stimulated long-lasting HSV-specific effector memory CD8+ T cells (TEM cells) and tissue-resident CD8+ T cells (TRM cells) locally in the vaginal mucocutaneous tissues (VM), and (iv) induced protective immunity against genital herpes infection and disease. As an alternative to currently used conventional adjuvants, the chemical- and biological-free laser adjuvant offers a well-tolerated, simple-to-produce method to enhance mass vaccination for widespread viral infections. IMPORTANCE Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) infect a large proportion of the world population. There is an urgent need for chemical-free and biological-free safe adjuvants that would advance mass vaccination against the widespread herpes infections. The present study demonstrates that immunization with a laser-assisted herpes peptide vaccine triggered skin mobilization of dendritic cells (DCs) that stimulated strong and long-lasting HSV-specific effector memory CD8+ T cells (TEM cells) and tissue-resident CD8+ T cells (TRM cells) locally in the vaginal mucocutaneous tissues. The induced local CD8+ T cell response was associated with protection against genital herpes infection and disease. These results draw attention to chemical- and biological-free laser adjuvants as alternatives to currently used conventional adjuvants to enhance mass vaccination for widespread viral infections, such as those caused by HSV-1 and HSV-2.
Epileptic nystagmus: a case study video-EEG correlation.

Epileptic nystagmus (EN) is an uncommon phenomenon characterized by repetitive and rapid saccades, in association with epileptic discharges. We present a critical video-EEG recording in a patient with occipital seizures that appeared clinically as EN. The subject, male, 70 years-old, was examined because of generalized tonic-clonic seizures, preceded by left cephalic version. These were controlled using i.v. PHT, but partial seizures persisted, which we recorded using video-EEG. Clinically, we observed episodes of left conjugate deviation of the eyes, accompanied by horizontal nystagmoid movements, with a rapid leftward component and visual hallucinations. The patient did not lose consciousness. Ictal EEG: spike rhythm in the posterior right occipito-temporal region extending to adjacent and contralateral regions, followed by post-discharge of slow waves. The video-EEG was interpreted as partial oculo-clonic status epilepticus of right temporo-occipital origin. Cranial MRI: old, bilateral hemorrhaging occipital contusions associated with previous cranial injury. The picture persisted for two days, and disappeared with administration of CBZ 600 mg/d. Our patient's nystagmus seemed to be related to the critical activity recorded in the right occipito-temporal region. The co-existence of visual hallucinations and the video-EEG correlation support this possibility. This phenomenon is probably due to epileptic activation of the cortical center of saccadic movements, with a rapid phase of nystagmus, contralateral to the focus, and a slow ipsilateral phase in association with a defect in the gaze-fixing system ("leaky neural integrator") [published with videosequences].
Heterogeneity in ornithine cytotoxicity of bovine retinal pigment epithelial cells in primary culture.

Gyrate atrophy of the choroid and retina is a chorioretinal degeneration caused by hyperornithinemia and a deficiency of ornithine-delta-aminotransferase (OAT). We recently showed that ornithine exhibits cytotoxicity to human retinal pigment epithelial (RPE) cell lines treated with the OAT inhibitor, 5-fluoromethylornithine (5-FMOrn), and suggested that this system may be an in vitro model of gyrate atrophy. In the present study, in order to apply this system to primary cultured RPE cells, we freshly prepared RPE cells from bovine eyes and studied the effect of ornithine on cell damage. Two phenotypes, epithelioid and fusiform, which coexisted in the primary culture and epithelioid phenotype cells, but not fusiform ones, were severely damaged and partially detached from the substrate by 10 m m ornithine and 0.5 m m 5-FMOrn. Neither ornithine nor 5-FMOrn alone exhibited such cytotoxicity to both phenotypes of RPE cells. Proline significantly prevented the ornithine-induced cytotoxicity. Epithelioid and fusiform phenotypes isolated from the primary culture showed different distribution of actin filaments. A combination of ornithine and 5-FMOrn time-dependently inhibited [(3)H]thymidine incorporation in the epithelioid, but not fusiform, cells. Proline prevented the inhibition of [(3)H]thymidine incorporation by ornithine in 5-FMOrn-treated epithelioid cells. Furthermore, l -azetidine-2-carboxylic acid, a collagen synthesis inhibitor, reduced [(3)H]thymidine incorporation in epithelioid, but not fusiform, cells, which was reversed by proline. These results demonstrate that the epithelioid phenotype of bovine RPE cells becomes susceptible to ornithine following inactivation of OAT. The phenotypic cells and its prevention by proline may provide insight into biochemical triggers that induce gyrate atrophy.
A Novel Exclusion Mechanism for Carbon Resource Partitioning in Aggregatibacter actinomycetemcomitans

ABSTRACT The bacterium Aggregatibacter actinomycetemcomitans is a common commensal of the human oral cavity and the putative causative agent of the disease localized aggressive periodontitis. A. actinomycetemcomitans is a slow-growing bacterium that possesses limited metabolic machinery for carbon utilization. This likely impacts its ability to colonize the oral cavity, where growth and community composition is mediated by carbon availability. We present evidence that in the presence of the in vivo relevant carbon substrates glucose, fructose, and lactate A. actinomycetemcomitans preferentially metabolizes lactate. This preference for lactate exists despite the fact that A. actinomycetemcomitans grows faster and obtains higher cell yields during growth with carbohydrates. The preference for lactate is mediated by a novel exclusion mechanism in which metabolism of lactate inhibits carbohydrate uptake. Coculture studies reveal that A. actinomycetemcomitans utilizes lactate produced by the oral bacterium Streptococcus gordonii, suggesting the potential for cross-feeding in the oral cavity.
Identification and genetic characterisation of melibiose-negative isolates of Streptococcus mutans.

Streptococcus mutans is frequently identified on the basis of phenotypic characteristics such as the ability to ferment carbohydrates. The usefulness of some of these identification tests may be limited in the case of isolates which are atypical with regard to their fermentation properties. We previously identified isolates of S. mutans which were unable to ferment melibiose, a characteristic which is included in some typing schemes. In all of these isolates there was a large chromosomal deletion which included the multiple sugar metabolism (msm) operon which encodes several genes involved in the uptake and metabolism of a number of sugars including melibiose. In the present study, sugar fermentation tests, ribotyping, colony hybridisation with DNA probes and polymerase chain reaction (PCR) were used to investigate the relatedness of these atypical isolates. The PCR and colony hybridisation procedures were based on amplification and detection of two genes: the wapA gene which encodes a surface protein found in all S. mutans strains and the gtfA gene which lies within the msm operon. The colony hybridisation and PCR results confirmed loss of the gtfA gene in the melibiose-negative isolates. Three new melibiose-negative isolates were also identified, but in only 2 of these was the gtfA gene absent, the third did not appear to have lost this region of the chromosome. Biotyping, as well as ribotyping based on an EcoRI digest of chromosomal DNA, revealed that the melibiose-negative isolates fell into a number of distinct groups. (ABSTRACT TRUNCATED AT 250 WORDS)
Stability analysis of craniovertebral junction fixation techniques.

BACKGROUND Craniovertebral arthrodesis in the upper cervical spine is challenging because of the high degree of mobility afforded by this region. A novel method for achieving atlantoaxial fixation with use of polyaxial screws inserted bilaterally into the lateral masses of C1 and transpedicularly into C2 with longitudinal rod connection has recently been introduced. The question remains as to whether this technique provides adequate stability when extended cephalad to include the occiput. The purpose of this study was to determine the primary stability afforded by this novel construct and compare its stability with the current standard of bilateral longitudinal plates combined with C1-C2 transarticular screws. METHODS We used ten fresh-frozen human cadaveric cervical spines (C0-C4). Pure moment loads were applied to the occiput, and C4 was constrained during the testing protocol. We evaluated four conditions: (1) intact, (2) destabilized by means of complete odontoidectomy, (3) stabilization with longitudinal plates with C1-C2 transarticular screw fixation, and (4) stabilization with a posterior rod system with C1 lateral mass screws and C2 pedicle screws. Rigid-body three-dimensional rotations were detected by stereophotogrammetry by means of a three-camera system with use of marker triads. The range of motion data (C0-C2) for each fixation scenario was calculated, and a statistical analysis was performed. RESULTS Destabilization of the specimen significantly increased C0-C2 motion in both flexion-extension and lateral bending (p < 0.05). Both fixation constructs significantly reduced motion in the destabilized spine by over 90% for all motions tested (p < 0.05). No significant differences were detected between the two constructs in any of the three rotational planes. CONCLUSIONS Both hardware systems provide equivalent construct stability in the immediate postoperative period when it is critical for the eventual success of a craniovertebral arthrodesis. On the basis of this work, we believe that the decision to use either construct should be determined by clinical rather than biomechanical concerns.
Effect of temperature, relative humidity and rainfall on dengue fever and leptospirosis infections in Manila, the Philippines

SUMMARY Dengue fever (DF) and leptospirosis are serious public problems in tropical regions, especially in Manila, the Philippines. In attempting to understand the causes of DF and leptospirosis seasonality, meteorological factors have been suspected, but quantitative correlation between seasonality and meteorological factors has not been fully investigated. In this study, we investigated correlation of temporal patterns of reported numbers of laboratory-confirmed cases of both DF and leptospirosis with meteorological conditions (temperature, relative humidity, rainfall) in Manila. We used time-series analysis combined with spectral analysis and the least squares method. A 1-year cycle explained underlying variations of DF, leptospirosis and meteorological data. There was a peak of the 1-year cycle in temperature during May, followed by maxima in rainfall, relative humidity and number of laboratory-confirmed DF and leptospirosis cases. This result suggests that DF and leptospirosis epidemics are correlated not only with rainfall but also relative humidity and temperature in the Philippines. Quantifying the correlation of DF and leptospirosis infections with meteorological conditions may prove useful in predicting DF and leptospirosis epidemics, and health services should plan accordingly.
Classifying Schizotypy Using an Audiovisual Emotion Perception Test and Scalp Electroencephalography

Schizotypy refers to the personality trait of experiencing “psychotic” symptoms and can be regarded as a predisposition of schizophrenia-spectrum psychopathology (Raine, 1991). Cumulative evidence has revealed that individuals with schizotypy, as well as schizophrenia patients, have emotional processing deficits. In the present study, we investigated multimodal emotion perception in schizotypy and implemented the machine learning technique to find out whether a schizotypy group (ST) is distinguishable from a control group (NC), using electroencephalogram (EEG) signals. Forty-five subjects (30 ST and 15 NC) were divided into two groups based on their scores on a Schizotypal Personality Questionnaire. All participants performed an audiovisual emotion perception test while EEG was recorded. After the preprocessing stage, the discriminatory features were extracted using a mean subsampling technique. For an accurate estimation of covariance matrices, the shrinkage linear discriminant algorithm was used. The classification attained over 98% accuracy and zero rate of false-positive results. This method may have important clinical implications in discriminating those among the general population who have a subtle risk for schizotypy, requiring intervention in advance.
Optimization Design of 2.5D TSV Package Using Thermo-Electrical Co-Simulation Method

In this paper, a 2.5D TSV (through silicon via) package is de-signed for handheld device. A high performance Application Processor die and a Memory die with the sizes of 7.535×7.616×0.15 mm3 and 7.336×3.604×0.15 mm3, respectively, are integrated on a silicon interposer with a large number of TSVs. The backside and front of the interposer have one and two layers of redistribution layer (RDL), respectively. Each layer of RDL is about 3~5 μm and the minimum line width / pitch of the RDL in the interposer are 10 μm / 10 μm. In order to investigate the thermal performance of the package, IR drop of Power and Ground (P/G) Nets of the Processor and Memory dies, and the mutual effects of them, the paper conducts the following researches: First of all, only thermal simulation is done to investigate the thermal performance of the 2.5D TSV package using Cadence Sigrity PowerDC. The highest junction temperatures of Processor and Memory dies are evaluated. When the ambient temperature is 25°C, the junction temperatures of Processor and Memory dies are 62.7°C and 56°C, respectively, which are relatively higher for handheld device. Then, thermal and optimization designs are conducted to improve the thermal performance of the 2.5D TSV package. An aluminum heat spreader is employed, attached to the top surface of the 2.5D TSV package through high heat conductive thermal interface material (TIM). The effects of heat spreader size on the highest junction temperatures of Processor and Memory dies are studied and a heat spreader size of 60×60×2 mm3 is chosen. Thirdly, thermal simulation and thermo-electrical co-simulation are compared to study the effects of P/G Nets of the both dies on the thermal performance of the 2.5D TSV package. It is found that P/G Nets could increase the junction temperature of the both dies. Fourthly, IR drop analysis and thermo-electrical co-simulation are compared to study the effects of the heat dissipation issues of the package on the IR drop of P/G Nets of the both dies. The study shows that the heat could increase the IR drop of P/G Nets of the both dies and IR drop of VDDCPU of the Processor die is the biggest. Fifthly, aiming at the VDDCPU of Processor die, optimization design is carried out to reduce the IR drop of VDDCPU. After optimization, IR drop of VDDCPU decreases by 45.3%. IR drop decreases to an acceptable value. Therefore, P/G Nets of the dies should be considered when conducting thermal simulation of the package, and heat dissipation issues of the package should also be considered when analyzing IR drop of P/G Nets of the dies.
Predictors of anxiety and depression following pregnancy termination: a longitudinal five‐year follow‐up study

Background. The aims of the study were to assess anxiety and depression in women who had experienced either a miscarriage or an induced abortion, to compare the women's level of distress with that of a general population sample, and to find predictors of anxiety and depression six months and five years after the event. Methods. A prospective, longitudinal follow‐up study. Women who experienced miscarriage (n=40) and induced abortion (n=80) were interviewed ten days (T1), six months (T2), two years (T3), and five years (T4) after the event. On each occasion, they completed the Hospital Anxiety and Depression Scale and the Life Events Scale. Paired‐sample t‐test, logistic regression, and multiple linear regression statistical tests were used. Results. Women with miscarriage had significantly more anxiety and depression at T1 than the general population, while women with induced abortion had significantly more anxiety at all time points and more depression at T1 and T2. In both groups, important predictors of anxiety and depression at T2 and T4 were recent life events and poor former psychiatric health. Childbirth events between T1 and T4 had no significant influence on the scores. For women with induced abortion, doubt about the decision to abort was related to depression at T2 (p<0.05), while a negative attitude towards induced abortion was associated with anxiety at T2 (p<0.05) and T4 (p<0.05). Conclusion. Correlates of anxiety and depression may be used to better identify women who are at risk of negative psychological responses following pregnancy termination.
The protein C pathway

ObjectiveTo examine the role of the protein C anticoagulant pathway in the regulation of microvascular thrombosis. The mechanisms by which inflammation impairs the function of this pathway are also reviewed; conversely, we will survey emerging knowledge of the multiple mechanisms by which the protein C anticoagulant pathway can control the inflammatory response. Data SourcesThe information reviewed here was taken from the primary literature, including recent abstracts. Study SelectionAll studies that bear directly on the interrelationship between the protein C anticoagulant pathway and inflammation were included, as was a summary of the initial clinical experience with protein C/activated protein C therapy in sepsis. Data Extraction and SynthesisThe results from each of the experimental approaches are summarized. Clinical experience with protein C supplementation in sepsis, although promising, is still in the early stages of study. ConclusionsThe protein C anticoagulant pathway is a major mechanism in controlling microvascular thrombosis. Protein C deficiency that can occur in sepsis facilitates thrombin generation in the microvasculature, probably augmenting inflammatory responses and contributing to endothelial cell dysfunction. Animal studies and preliminary clinical results suggest that protein C/ activated protein C supplementation may be useful in reversing microvascular dysfunction.
Generation and Improvement of Effector Function of a Novel Broadly Reactive and Protective Monoclonal Antibody against Pneumococcal Surface Protein A of Streptococcus pneumoniae

A proof-of-concept study evaluating the potential of Streptococcus pneumoniae Pneumococcal Surface Protein A (PspA) as a passive immunization target was conducted. We describe the generation and isolation of several broadly reactive mouse anti-PspA monoclonal antibodies (mAbs). MAb 140H1 displayed (i) 98% strain coverage, (ii) activity in complement deposition and opsonophagocytic killing (OPK) assays, which are thought to predict the in vivo efficacy of anti-pneumococcal mAbs, (iii) efficacy in mouse sepsis models both alone and in combination with standard-of-care antibiotics, and (iv) therapeutic activity in a mouse pneumonia model. Moreover, we demonstrate that antibody engineering can significantly enhance anti-PspA mAb effector function. We believe that PspA has promising potential as a target for the therapy of invasive pneumococcal disease by mAbs, which could be used alone or in conjunction with standard-of-care antibiotics.
Male Infertility Is Responsible for Nearly Half of the Extinction Observed in the Mouse Collaborative Cross

The goal of the Collaborative Cross (CC) project was to generate and distribute over 1000 independent mouse recombinant inbred strains derived from eight inbred founders. With inbreeding nearly complete, we estimated the extinction rate among CC lines at a remarkable 95%, which is substantially higher than in the derivation of other mouse recombinant inbred populations. Here, we report genome-wide allele frequencies in 347 extinct CC lines. Contrary to expectations, autosomes had equal allelic contributions from the eight founders, but chromosome X had significantly lower allelic contributions from the two inbred founders with underrepresented subspecific origins (PWK/PhJ and CAST/EiJ). By comparing extinct CC lines to living CC strains, we conclude that a complex genetic architecture is driving extinction, and selection pressures are different on the autosomes and chromosome X. Male infertility played a large role in extinction as 47% of extinct lines had males that were infertile. Males from extinct lines had high variability in reproductive organ size, low sperm counts, low sperm motility, and a high rate of vacuolization of seminiferous tubules. We performed QTL mapping and identified nine genomic regions associated with male fertility and reproductive phenotypes. Many of the allelic effects in the QTL were driven by the two founders with underrepresented subspecific origins, including a QTL on chromosome X for infertility that was driven by the PWK/PhJ haplotype. We also performed the first example of cross validation using complementary CC resources to verify the effect of sperm curvilinear velocity from the PWK/PhJ haplotype on chromosome 2 in an independent population across multiple generations. While selection typically constrains the examination of reproductive traits toward the more fertile alleles, the CC extinct lines provided a unique opportunity to study the genetic architecture of fertility in a widely genetically variable population. We hypothesize that incompatibilities between alleles with different subspecific origins is a key driver of infertility. These results help clarify the factors that drove strain extinction in the CC, reveal the genetic regions associated with poor fertility in the CC, and serve as a resource to further study mammalian infertility.