Miracle-dz/UniFAR-FTUs huggingface dataset:
Effectiveness of ultra-rapid dose titration of clozapine for treatment-resistant bipolar mania: case series

Treatment of severe and refractory manic episodes in hospital settings can occasionally be very difficult. In particular, severely excited patients showing aggressive, hostile, impulsive behaviours frequently require physical restraint and seclusion, high doses of antipsychotics and benzodiazepines, and sometimes, electroconvulsive therapy. Hospital stay is generally prolonged and such patients cause great emotional distress for other patients in the ward and clinical staff involved in their care. Here we report on three patients with a diagnosis of bipolar disorder and one patient with a diagnosis of schizoaffective disorder bipolar subtype, all of whom were hospitalized for severe manic episodes with psychotic features. These patients were extremely difficult to manage in the ward as no response could be obtained in the first week of treatment despite high doses of antipsychotics and benzodiazepine administration. The introduction and rapid titration of clozapine proved remarkably effective and was well tolerated in the acute management of these patients. We observed that clozapine had a superior and fast mood stabilization effect with rapid titration and could be extremely helpful in the management of such patients.
An Optimal Torque Vectoring Control for Vehicle Applications via Real-Time Constraints

A generalized integrated control strategy for vehicle dynamics using an optimal torque vectoring control approach is extended in this paper. The central objective of this approach is to generate optimal additional tire forces and yaw moment over the vehicle through the application of individual wheel torque to keep the vehicle on a target path. This is achieved by minimizing the error between the actual and target forces and moment at the center of gravity (CG). In this paper, this methodology is extended to a constrained optimal control approach that handles additional real-time constraints, which has several vehicle control applications. An online optimization strategy is used to solve the resulting constrained optimization problem that gives the necessary tire force adjustments at the tire level. Some typical applications are 1) differential braking on all wheels, which is applicable to both electric and conventional cars and 2) hybrid torque vectoring on the front wheels and differential braking on the rear wheels. Both simulations and experimental results show the usefulness of this approach of handling constraints with this optimal torque vectoring control.
Cardiotrophin-1 Promotes a High Survival Rate in Rabbits with Lethal Fulminant Hepatitis of Viral Origin

ABSTRACT Rabbit hemorrhagic disease virus (RHDV) causes lethal fulminant hepatitis closely resembling acute liver failure (ALF) in humans. In this study, we investigated whether cardiotrophin-1 (CT-1), a cytokine with hepatoprotective properties, could attenuate liver damage and prolong survival in virus-induced ALF. Twenty-four rabbits were infected with 2 × 104 hemagglutination units of RHDV. Twelve received five doses of CT-1 (100 μg/kg) starting at 12 h postinfection (hpi) (the first three doses every 6 h and then two additional doses at 48 and 72 hpi), while the rest received saline. The animals were analyzed for survival, serum biochemistry, and viral load. Another cohort (n = 22) was infected and treated similarly, but animals were sacrificed at 30 and 36 hpi to analyze liver histology, viral load, and the expression of factors implicated in liver damage and repair. All infected rabbits that received saline died by 60 hpi, while 67% of the CT-1-treated animals survived until the end of the study. Treated animals showed improved liver function and histology, while the viral loads were similar. In the livers of CT-1-treated rabbits we observed reduction of oxidative stress, diminished PARP1/2 and JNK activation, and decreased inflammatory reaction, as reflected by reduced expression of tumor necrosis factor alpha, interleukin-1β, Toll-like receptor 4, VCAM-1, and MMP-9. In addition, CT-1-treated rabbits exhibited marked upregulation of TIMP-1 and increased expression of cytoprotective and proregenerative growth factors, including platelet-derived growth factor B, epidermal growth factor, platelet-derived growth factor receptor β, and c-Met. In conclusion, in a lethal form of acute viral hepatitis, CT-1 increases animal survival by attenuating inflammation and activating cytoprotective mechanisms, thus representing a promising therapy for ALF of viral origin.
Ayahuasca, dimethyltryptamine, and psychosis: a systematic review of human studies

Ayahuasca is a hallucinogen brew traditionally used for ritual and therapeutic purposes in Northwestern Amazon. It is rich in the tryptamine hallucinogens dimethyltryptamine (DMT), which acts as a serotonin 5-HT2A agonist. This mechanism of action is similar to other compounds such as lysergic acid diethylamide (LSD) and psilocybin. The controlled use of LSD and psilocybin in experimental settings is associated with a low incidence of psychotic episodes, and population studies corroborate these findings. Both the controlled use of DMT in experimental settings and the use of ayahuasca in experimental and ritual settings are not usually associated with psychotic episodes, but little is known regarding ayahuasca or DMT use outside these controlled contexts. Thus, we performed a systematic review of the published case reports describing psychotic episodes associated with ayahuasca and DMT intake. We found three case series and two case reports describing psychotic episodes associated with ayahuasca intake, and three case reports describing psychotic episodes associated with DMT. Several reports describe subjects with a personal and possibly a family history of psychosis (including schizophrenia, schizophreniform disorders, psychotic mania, psychotic depression), nonpsychotic mania, or concomitant use of other drugs. However, some cases also described psychotic episodes in subjects without these previous characteristics. Overall, the incidence of such episodes appears to be rare in both the ritual and the recreational/noncontrolled settings. Performance of a psychiatric screening before administration of these drugs, and other hallucinogens, in controlled settings seems to significantly reduce the possibility of adverse reactions with psychotic symptomatology. Individuals with a personal or family history of any psychotic illness or nonpsychotic mania should avoid hallucinogen intake.
Extended-release methylphenidate monotherapy in patients with comorbid social anxiety disorder and adult attention-deficit/hyperactivity disorder: retrospective case series

Background: The relationship between social anxiety disorder (SAD) and attention-deficit/hyperactivity disorder (ADHD) is a subject which has recently become a topic of interest for research. Methods: In this study, 20 patients with comorbid SAD and adult ADHD who were treated with extended-release methylphenidate monotherapy were evaluated retrospectively. Results: Clinical response for both ADHD and SAD symptoms was observed in 17 of 20 patients. Overall, one patient did not respond to treatment and two patients dropped out of treatment at the beginning due to adverse effects. Conclusion: Extended-release methylphenidate improved both SAD and ADHD symptoms and was generally well tolerated. Further studies are required to investigate the relationship between SAD and ADHD.
Role of Ubiquitin in Parainfluenza Virus 5 Particle Formation

ABSTRACT Ubiquitin is important for the budding of many retroviruses and other enveloped viruses, but the precise role of ubiquitin in virus budding remains unclear. Here, we characterized the ubiquitination of the matrix (M) protein of a paramyxovirus, parainfluenza virus 5 (PIV5). The PIV5 M protein (but not the PIV5 nucleocapsid protein) was found to be targeted for monoubiquitination in transfected mammalian cells. Major sites of ubiquitin attachment identified by mass spectrometry analysis were lysine residues at amino acid positions 79/80, 130, and 247. The cumulative mutation of lysine residues 79, 80, and 130 to arginines led to an altered pattern of M protein ubiquitination and impaired viruslike particle (VLP) production. However, the cumulative mutation of lysine residues 79, 80, 130, and 247 to arginines restored M protein ubiquitination and VLP production, suggesting that ubiquitin is attached to alternative sites on the M protein when the primary ones have been removed. Additional lysine residues were targeted for mutagenesis based on the UbiPred algorithm. An M protein with seven lysine residues changed to arginines exhibited altered ubiquitination and poor VLP production. A recombinant virus encoding an M protein with seven lysines mutated was generated, and this virus exhibited a 6-fold-reduced maximum titer, with the defect being attributed mainly to the budding of noninfectious particles. The recombinant virus was assembly deficient, as judged by the redistribution of viral M and hemagglutinin-neuraminidase proteins in infected cells. Similar assembly defects were observed for the wild-type (wt) virus after treatment with a proteasome inhibitor. Collectively, these findings suggest that the monoubiquitination of the PIV5 M protein is important for proper virus assembly and for the budding of infectious particles.
The safety and pharmacokinetics of rapid iloprost aerosol delivery via the BREELIB nebulizer in pulmonary arterial hypertension

The BREELIB nebulizer was developed for iloprost to reduce inhalation times for patients with pulmonary arterial hypertension (PAH). This multicenter, randomized, unblinded, four-part study compared inhalation time, pharmacokinetics, and acute tolerability of iloprost 5 µg at mouthpiece delivered via BREELIB versus the standard I-Neb nebulizer in 27 patients with PAH. The primary safety outcome was the proportion of patients with a maximum increase in heart rate (HR) ≥ 25% and/or a maximum decrease in systolic blood pressure ≥ 20% within 30 min after inhalation. Other safety outcomes included systolic, diastolic, and mean blood pressure, HR, oxygen saturation, and adverse events (AEs). Median inhalation times were considerably shorter with BREELIB versus I-Neb (2.6 versus 10.9 min; n = 24). Maximum iloprost plasma concentration and systemic exposure (area under the plasma concentration–time curve) were 77% and 42% higher, respectively, with BREELIB versus I-Neb. Five patients experienced a maximum systolic blood pressure decrease ≥ 20%, four with BREELIB (one mildly and transiently symptomatic), and one with I-Neb; none required medical intervention. AEs reported during the study were consistent with the known safety profile of iloprost. The BREELIB nebulizer offers reduced inhalation time, good tolerability, and may improve iloprost aerosol therapy convenience and thus compliance for patients with PAH.
Complications associated with the use of oral anticoagulation in patients with pulmonary arterial hypertension from two referral centers

Anticoagulants are widely used in patients with pulmonary arterial hypertension (PAH) to prolong survival. However, there is a lack of robust evidence demonstrating the benefits of anticoagulants in PAH patients and very little is known about the complications of their use in this population. The objective of this study is to compare the safety of routine administration of oral anticoagulants between PAH patients who were and were not treated with oral anticoagulants. This observational, retrospective cohort study included consecutive patients with confirmed PAH from two centers: Brigham and Women’s Hospital in Boston and Hospital Universitario La Paz in Madrid from January 2009 to August 2015. The study group comprised patients who received therapeutic anticoagulation; patients who had never received anticoagulants were placed in the control group. Of the 201 included patients, 60.2% were treated with oral anticoagulants and 39.8% were not treated. The hazard ratio for major bleeding was 2.7 (95% confidence interval [CI] = 1.1–6.8; P = 0.036). The incidence rate for the anticoagulation group was 4.7 per 100 patient-years (95% CI = 2.5–8.0). The most frequent major hemorrhage was gastrointestinal bleeding with 24 cases (72.7%). Prior bleeding, poor anticoagulation, HAS-BLED score ≥3, diabetes, and number of medications were factors that increased the risk of major bleeding in patients using anticoagulants. The harmful effects of anticoagulants could outweigh the benefits in PAH patients. Therefore, anticoagulants should be prescribed on a case-by-case basis and should not be systematically recommended.
Potent Autologous and Heterologous Neutralizing Antibody Responses Occur in HIV-2 Infection across a Broad Range of Infection Outcomes

ABSTRACT Few studies have explored the role of neutralizing antibody (NAb) responses in controlling HIV-2 viremia and disease progression. Using a TZM-bl neutralization assay, we assessed heterologous and autologous NAb responses from a community cohort of HIV-2-infected individuals with a broad range of disease outcomes in rural Guinea-Bissau. All subjects (n = 40) displayed exceptionally high heterologous NAb titers (50% inhibitory plasma dilution or 50% inhibitory concentration [IC50], 1:7,000 to 1:1,000,000) against 5 novel primary HIV-2 envelopes and HIV-2 7312A, whereas ROD A and 3 primary envelopes were relatively resistant to neutralization. Most individuals also showed high autologous NAb against contemporaneous envelopes (78% of plasma-envelope combinations in 69 envelopes from 21 subjects), with IC50s above 1:10,000. No association between heterologous or autologous NAb titer and greater control of HIV-2 was found. A subset of envelopes was found to be more resistant to neutralization (by plasma and HIV-2 monoclonal antibodies). These envelopes were isolated from individuals with greater intrapatient sequence diversity and were associated with changes in potential N-linked glycosylation sites but not CD4 independence or CXCR4 use. Plasma collected from up to 15 years previously was able to potently neutralize recent autologous envelopes, suggesting a lack of escape from NAb and the persistence of neutralization-sensitive variants over time, despite significant NAb pressure. We conclude that despite the presence of broad and potent NAb responses in HIV-2-infected individuals, these are not the primary forces behind the dichotomous outcomes observed but reveal a limited capacity for adaptive selection and escape from host immunity in HIV-2 infection.
The Andes Hantavirus NSs Protein Is Expressed from the Viral Small mRNA by a Leaky Scanning Mechanism

ABSTRACT The small mRNA (SmRNA) of all Bunyaviridae encodes the nucleocapsid (N) protein. In 4 out of 5 genera in the Bunyaviridae, the smRNA encodes an additional nonstructural protein denominated NSs. In this study, we show that Andes hantavirus (ANDV) SmRNA encodes an NSs protein. Data show that the NSs protein is expressed in the context of an ANDV infection. Additionally, our results suggest that translation initiation from the NSs initiation codon is mediated by ribosomal subunits that have bypassed the upstream N protein initiation codon through a leaky scanning mechanism.
ANALYSIS OF VENTOUSE DELIVERIES AT TERTIARY CARE TEACHING HOSPITAL

Background :-Instrumental deliveries are conducted to assist or expediate the delivery of the baby in second stage of labour. Ventouse deliveries are on rise due to its preferance over obstetric forceps.Relative safety and requirement of less technical skill ,could be the two main reasons for its preferance over forceps. Results :-The incidence of ventouse deliveries was 0.73%. Common indications of ventouse application were maternal exhaustion,previous caesarean section, fetal distress and eclampsia. Six percent cases had ventouse related complications.One case had third degree perineal tear and one baby had cephal hematoma and intracranial hemorrhage.Failure of ventouse, requiring caesarean section was observed in 4% of cases. Apgar score of babies delivered by ventouse, performed for prolonged second stage was lower, than when it was performed for prophylactic indication.Overall neonatal outcome was satisfactory. Duration of hospital stay was not affected by ventouse delivery. Conclusion :-Careful selection of cases and adequate training of postgraduate students during residency under direct supervision of senior experienced obstetrician can reduce the rate of failed ventouse and related complications.Ventouse remains a good alternative to obstetric forceps in situation like proloned second stage and those situations which demand shortening of second stage of labour like maternal hypertensive diseases and rheumatic heart diseases.
Frame-based compression of animated meshes in MPEG-4

This paper presents a new compression technique for 3D dynamic meshes, referred to as FAMC - frame-based animated mesh compression, promoted within the MPEG-4 standard as amendment 2 of part 16 AFX (animation framework extension). The FAMC approach combines a model-based motion compensation strategy, with transform/predictive coding of residual errors. First, a skinning motion compensation model is automatically computed from a frame-based representation and then encoded. Subsequently, either 1) DCT/lifting wavelets or 2) layer-based predictive coding is employed to exploit remaining spatio-temporal correlations in the residual signal. The proposed encoder offers high compression performances (gains in bit rate of 60% with respect to the previous MPEG-4 technique and of 20% to 40% with respect to state-of-the-art approaches) and is well suited for compressing both geometric and photometric (normal vectors, colors.) attributes. In addition, the FAMC method supports a rich set of functionalities including streaming, scalability (spatial, temporal and quality) and progressive transmission.
Cognitive function recovery rate in early postoperative period: comparison of propofol, sevoflurane and isoflurane anesthesia

Introduction: There is no simple answer to the question as to when the brain function is back to normal after anaesthesia. Research done so far has identified different factors influencing the rate of cognitive function recovery and type of anaesthetic as one of those factors.Methods: This study encountered 90 patients hospitalized in neurosurgical department of University Clinical Centre Tuzla in period from October 2011 to may 2012 year. Aim of the study was to compare influence of three different anesthetics (propofol, isofl urane and sevofl urane) on recovery rate of cognitive performance 1, 5 and 10 minutes following extubation. Assessment of cognitive functions was preformed using the short Orientation-Memory-Concentration (OMC) Test. All patients included in the study underwent lumbar microdiscectomy surgery and were allocated to one of three groups: propofol, sevoflurane and isoflurane.Results: Trough comparison of OMC test values there is obvious superiority in recovery of cognitive functions between propofol group and inhaled anesthetic group, after 1 minute (p = 0.008) and after 5 minutes (p =0.009). Comparison of propofol and isoflurane anesthesia shows significantly faster recovery of cognitive performance in propofol group (after 1 minute p = 0.002, 5 minutes p = 0.004, 10 minutes p = 0.038). Faster recovery of cognitive function is present in sevoflurane compared to isoflurane group only 1 minute after extubation p = 0.049. Conclusions: Fastest recovery of cognitive performance appears after propofol anesthesia, than follows sevofl urane based anesthesia and after that isoflurane anesthesia.
Transmissible Gastroenteritis Coronavirus RNA-Dependent RNA Polymerase and Nonstructural Proteins 2, 3, and 8 Are Incorporated into Viral Particles

ABSTRACT Coronavirus replication and transcription are processes mediated by a protein complex, with the RNA-dependent RNA polymerase (RdRp) as a main component. Proteomic analysis of highly purified transmissible gastroenteritis virus showed the RdRp to be a component of the viral particles. This finding was confirmed by Western blotting, immunofluorescence, and immunoelectron microscopy analyses. Interestingly, the replicase nonstructural proteins 2, 3, and 8 colocalized with the RdRp in the viral factories and were also incorporated into the virions.
Expression of Cytokeratin Subtypes and Vimentin in Squamous Cell Carcinoma of the Floor of the Mouth and the Mobile Tongue

Objectives: The assessment of the expression patterns of cytokeratin polypeptides (Cks) and vimentin in normal epithelium of the mobile tongue and floor of the mouth, squamous cell carcinomas and their lymph node metastases. Material and Methods: Chain-specific monoclonal antibodies to various Cks and vimentin were used, employing the immunoperoxidase technique. Results and Conclusions: Profound changes in the expression of pre-existing Cks and de novo expression of simple epithelium-related Cks and of vimentin occurred upon malignant transformation and tumor progression. Changes were mainly related to the degree of cellular differentiation, tumor cell morphology and tumor growth pattern. Low-grade tumors showed a pronounced decrease of the stratification Cks 4 and 13, and an increase of Cks 14, 16, and 17. With increasing tumor grade, expression of Cks 16 and 17 decreased. De novo expression of Cks 8 and 18 and of vimentin was most marked in high-grade tumors, in tumors with a basaloid phenotype and in tumors growing in small infiltrating tumor fields; it was proposed to be associated with poor prognosis.
Identification of New Viral Genes and Transcript Isoforms during Epstein-Barr Virus Reactivation using RNA-Seq

ABSTRACT Using an enhanced RNA-Seq pipeline to analyze Epstein-Barr virus (EBV) transcriptomes, we investigated viral and cellular gene expression in the Akata cell line following B-cell-receptor-mediated reactivation. Robust induction of EBV gene expression was observed, with most viral genes induced >200-fold and with EBV transcripts accounting for 7% of all mapped reads within the cell. After induction, hundreds of candidate splicing events were detected using the junction mapper TopHat, including a novel nonproductive splicing event at the gp350/gp220 locus and several alternative splicing events at the LMP2 locus. A more detailed analysis of lytic LMP2 transcripts showed an overall lack of the prototypical type III latency splicing events. Analysis of nuclear versus cytoplasmic RNA-Seq data showed that the lytic forms of LMP2, EBNA-2, EBNA-LP, and EBNA-3A, -3B, and -3C have higher nuclear-to-cytoplasmic accumulation ratios than most lytic genes, including classic late genes. These data raise the possibility that at least some lytic transcripts derived from these latency gene loci may have unique, noncoding nuclear functions during reactivation. Our analysis also identified two previously unknown genes, BCLT1 and BCRT2, that map to the BamHI C-region of the EBV genome. Pathway analysis of cellular gene expression changes following B-cell receptor activation identified an inflammatory response as the top predicted function and ILK and TREM1 as the top predicted canonical pathways.