Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical, Pathologic, Immunohistochemical, and Virologic Findings of Eastern Equine Encephalomyelitis in Two Horses

Natural eastern equine encephalitis alphavirus (EEEV) infection was diagnosed in two adult horses with anorexia and colic, changes in sensorium, hyperexcitability, and terminal severe depression. Myocardium, tunica muscularis of stomach, intestine, urinary bladder, and spleen capsule had coagulative necrosis and perivascular lymphocytic infiltrate. Central nervous system (CNS) lesions were diffuse polioencephalomyelitis with leptomeningitis characterized by perivascular T lymphocyte cuffing, marked gliosis, neuronophagia, and multifocal microabscesses. Lesions were more prominent within cerebral cortex, thalamus, hypothalamus, and mesencephalon. EEEV was identified in the cytoplasm of cardiac myocytes and smooth muscle cells of spleen, stomach, intestine, urinary bladder, blood vessels, and dendritic cells. In the CNS, EEEV-positive cells included neurons, astrocytes, oligodendrocytes, microglia, and neutrophils. EEEV was isolated from the CNS of both horses. The detailed description of the encephalic and spinal EEEV localization and the findings of EEEV in extraneural tissues contribute to the understanding of this important multisystemic zoonotic disease.
Characterization of Structural Features and Diversity of Variable-Region Determinants of Related Quaternary Epitopes Recognized by Human and Rhesus Macaque Monoclonal Antibodies Possessing Unusually Potent Neutralizing Activities

ABSTRACT A series of potently neutralizing monoclonal antibodies (MAbs) that target quaternary epitopes on the native Env trimer have recently been described. A common feature shared by these antibodies is the critical involvement of sites in both the V2 and V3 variable domains in antibody recognition. In this study the gp120 variable-region determinants were mapped for eight rhesus macaque monoclonal antibodies (RhMAbs) possessing potently neutralizing activity specific for a quaternary target in SF162 Env and compared to those originally identified for human MAb 2909. These studies showed that determinants for the epitopes defined by the RhMAbs differed in both the V2 (positions 160, 167, and 169) and V3 (positions 313 and 315) regions from 2909, and in a number of cases, from each other. Attempts to reconstitute expression of these epitopes on the cell surface by cotransfecting Envs containing either the V2 or the V3 determinant of the epitope were not successful, suggesting that these epitopes were expressed on individual protomers in a trimer-dependent manner. Several of the V2 positions found to be critical for expression of these quaternary epitopes also significantly affected exposure and neutralization sensitivity of targets in the V3 and CD4-binding domains. These results demonstrated a considerable diversity in the fine structure of this class of epitopes and further suggested a potentially important relationship between the expression of such quaternary epitopes and V1/V2-mediated masking of immunodominant epitopes.
Biomechanical modeling of the human head for physically based, nonrigid image registration

The accuracy of image-guided neurosurgery generally suffers from brain deformations due to intraoperative changes. These deformations cause significant changes of the anatomical geometry (organ shape and spatial interorgan relations), thus making intraoperative navigation based on preoperative images error prone. In order to improve the navigation accuracy, the authors developed a biomechanical model of the human head based on the finite element method, which can be employed for the correction of preoperative images to cope with the deformations occurring during surgical interventions. At the current stage of development, the two-dimensional (2-D) implementation of the model comprises two different materials, though the theory holds for the three-dimensional (3-D) case and is capable of dealing with an arbitrary number of different materials. For the correction of a preoperative image, a set of homologous landmarks must be specified which determine correspondences. These correspondences can be easily integrated into the model and are maintained throughout the computation of the deformation of the preoperative image. The necessary material parameter values have been determined through a comprehensive literature study. The authors' approach has been tested for the case of synthetic images and yields physically plausible deformation results. Additionally, they carried out registration experiments with a preoperative MR image of the human head and a corresponding postoperative image simulating an intraoperative image. The authors found that their approach yields good prediction results, even in the case when correspondences are given in a relatively small area of the image only.
Perineal reconstruction using pedicled vertical rectus abdominis myocutaneous flap (VRAM)

The perineal wound is a major source of morbidity after abdominoperineal resection (APR) for rectal cancer, particularly after preoperative irradiation. Myocutaneous flap reconstruction is a viable alternative to primary perineal wound repair providing well‐vascularized non‐irradiated tissue to fill the dead space, and improve wound healing.
Vagus nerve stimulation therapy in patients with autism spectrum disorder and intractable epilepsy: results from the vagus nerve stimulation therapy patient outcome registry.

OBJECT The purpose of this study was to determine the effectiveness of vagus nerve stimulation (VNS) therapy on quality-of-life (QOL) variables among patients with both autism spectrum disorder (ASD) and persistent or recurrent intractable epilepsy. METHODS Data were obtained from the VNS therapy patient outcome registry, which was established after US FDA approval of the VNS device in 1997 as a means of capturing open-label clinical data outside of protocol. The integrity of the systems for collecting and processing registry data was authenticated by an independent auditing agency. The effect of potential selection bias, however, remains uncertain. RESULTS Two cohorts were compared: 1) patients with epilepsy but without ASD (non-ASD [NASD] Group, 315 patients) who were being tracked in the registry (this cohort, which was controlled for age, included patients 20 years of age or younger); and 2) patients with a diagnosis of ASD who underwent implantation of the VNS device (ASD Group, 77 patients). Differences between the ASD and NASD groups were noted in the following categories: sex (male preponderance in ASD); normal imaging results (MR imaging results normal in ASD); depression (less common in ASD); behavioral problems (more common in ASD); neurological deficit (more common in ASD); mental retardation (more common in ASD); and developmental delay. The only QOL difference between the ASD and NASD groups was noted in mood at 12 months postimplant (mood was improved in ASD) (p = 0.04). There were no other differences in the QOL variables. CONCLUSIONS Patients with ASD and intractable epilepsy respond as favorably as all other patients receiving VNS therapy. In addition, they may experience a number of QOL improvements, some of which exceed those classically observed following placement of a VNS device.
Genomic diversity, population structure, and migration following rapid range expansion in the Balsam Poplar, Populus balsamifera

Rapid range expansions can cause pervasive changes in the genetic diversity and structure of populations. The postglacial history of the Balsam Poplar, Populus balsamifera, involved the colonization of most of northern North America, an area largely covered by continental ice sheets during the last glacial maximum. To characterize how this expansion shaped genomic diversity within and among populations, we developed 412 SNP markers that we assayed for a range‐wide sample of 474 individuals sampled from 34 populations. We complemented the SNP data set with DNA sequence data from 11 nuclear loci from 94 individuals, and used coalescent analyses to estimate historical population size, demographic growth, and patterns of migration. Bayesian clustering identified three geographically separated demes found in the Northern, Central, and Eastern portions of the species’ range. These demes varied significantly in nucleotide diversity, the abundance of private polymorphisms, and population substructure. Most measures supported the Central deme as descended from the primary refuge of diversity. Both SNPs and sequence data suggested recent population growth, and coalescent analyses of historical migration suggested a massive expansion from the Centre to the North and East. Collectively, these data demonstrate the strong influence that range expansions exert on genomic diversity, both within local populations and across the range. Our results suggest that an in‐depth knowledge of nucleotide diversity following expansion requires sampling within multiple populations, and highlight the utility of combining insights from different data types in population genomic studies.
[Fertilization of cryopreserved and thawed human oocytes (Cryo-Oo) by injection of spermatozoa (ICSI)--medical management of sterility and case report of a twin pregnancy].

It is reported on a twin pregnancy and parturition of a healthy girl and a healthy boy following the treatment of the mother by intracytoplasmic injection of spermatozoa (ICSI) into cryopreserved and thawed human oocytes (Cryo-Oo). The couple suffered from a primary sterility because of a severe subfertility of the husband and oligomenorrhea with anovulation of the wife. Before the couple contacted our center for the first time, several pretreatments had been carried out, e.g. intrauterine inseminations (IUI) with husband's and donor sperm and one cycle of in vitro fertilization (IVF) with intracytoplasmic sperm injection. This IVF/ICSI-cycle resulted in a tubal pregnancy. It must be noted that the patient showed in each treatment cycle a remarkable tendency to develop ovarian hyperstimulation syndromes (OHSS), even under stimulation with 50 mg clomiphen citrate. In 1997 we started the first treatment cycle for IVF/ICSI with GnIZH-analogues and FSH according to the long protocol. In spite of a low dosage of gonadotropins the patient again developed a impressive multifollicular growth that we decided, together with the couple, only to perform the oocyte retrieval and cryopreserve the collected eggs. For ethic considerations the couple did not consent in the freezing of pronuclear stages. Two months later we performed the transfer-cycle: after thawing of four oocytes, the intracytoplasmic injection of native spermatozoa led to the fertilization of three oocytes and a total of three preimplantation embryos was transferred one day later. Two weeks later the blood level of hCG was 518 IU/ml and an intact twin pregnancy developed. In July 1998, after 36 weeks of gestation, a healthy girl (2540 g) and an healthy boy (2375 g) were delivered by cesarean section. This case report and the experience with further 23 patients (6 pregnancies) demonstrate that ICSI with cryopreserved and thawed oocytes is an effective approach to avoid repetitive oocyte retrievals. The achievable pregnancy rates so far seem to be similar to frozen pronuclear stages, possibly even better. Under the specific regulations of the German Embryo Protection Act (ESchG)--i.e. freezing of embryos not allowed--this technique is worth being pursued with attention.
Acoustic stapedial reflexes in healthy neonates: normative data and test-retest reliability.

BACKGROUND The acoustic stapedial reflex (ASR) test provides useful information about the function of the auditory system. While it is frequently used with adults and children in a clinical setting, its use with young infants is limited. Presently, there are few data for neonates and inadequate research into the test-retest reliability of the ASR test. PURPOSE This study aimed to establish normative data and evaluate the test-retest reliability of the ASR test in healthy neonates. RESEARCH DESIGN A cross-sectional experimental design was used to establish ASR normative data and assess the test-retest reliability of ASR thresholds obtained from healthy neonates. STUDY SAMPLE Sixty-eight full-term neonates with mean chronological age of 2.5 days (SD = 1.8 day), who passed the automated auditory brainstem response, transient evoked otoacoustic emission, and high frequency (1 kHz) tympanometry (HFT) tests. DATA COLLECTION AND ANALYSIS One randomly selected ear from each neonate was tested using TEOAE (transient evoked otoacoustic emission), HFT, and ASR tests using a 1 kHz probe tone. ASR thresholds were elicited by presenting pure tones of 0.5, 2, and 4 kHz and broadband noise (BBN) separately to the test ear in an ipsilateral stimulation mode. The ASR procedure was repeated to acquire retest data within the same testing session. Descriptive statistics, χ2, and analysis of variance with repeated measures tests were used to analyze ASR data. RESULTS All neonates exhibited ASR when stimulated by tonal stimuli or BBN. The mean ASRTs (acoustic stapedial reflex thresholds) for the 0.5, 2, and 4 kHz tones were 81.6 ± 7.9, 71.3 ± 7.9, and 65.4 ± 8.7 dB HL, respectively. The mean ASRT for the BBN was estimated to be smaller than 57.2 dB HL, given the limitation of the equipment. The 95th percentiles of the ASRT were 95, 85, 80, and 75 dB HL for the 0.5, 2, and 4 kHz and BBN, respectively. The test-retest reliability of the ASR test for all stimuli was high, with no significant difference in mean ASRTs across the test and retest conditions. Test-retest differences were within 10 dB for more than 91% of ASRT data across all stimuli. There was a slight trend of ASRTs being more repeatable in the medium ASRT range than in the higher or lower range. CONCLUSIONS This study demonstrated that ASRTs obtained from healthy neonates were highly repeatable across test and retest sessions. Given the availability of normative data and the high test-retest reliability, the ASR test will be useful as a diagnostic tool in a battery of tests to evaluate the auditory function of neonates.
The Nuclear Orphan Receptor CAR-Retinoid X Receptor Heterodimer Activates the Phenobarbital-Responsive Enhancer Module of the CYP2B Gene

ABSTRACT PBREM, the phenobarbital-responsive enhancer module of the cytochrome P-450 Cyp2b10 gene, contains two potential nuclear receptor binding sites, NR1 and NR2. Consistent with the finding that anti-retinoid X receptor (RXR) could supershift the NR1-nuclear protein complex, DNA affinity chromatography with NR1 oligonucleotides enriched the nuclear orphan receptor RXR from the hepatic nuclear extracts of phenobarbital-treated mice. In addition to RXR, the nuclear orphan receptor CAR was present in the same enriched fraction. In the phenobarbital-treated mice, the binding of both CAR and RXR was rapidly increased before the induction of CYP2B10 mRNA. In vitro-translated CAR bound to NR1, but only in the presence of similarly prepared RXR. PBREM was synergistically activated by transfection of CAR and RXR in HepG2 and HEK293 cells when the NR1 site was functional. A CAR-RXR heterodimer has thus been characterized as atrans-acting factor for the phenobarbital-inducibleCyp2b10 gene.
Intracranial Hemorrhage Mortality in Atrial Fibrillation Patients Treated With Dabigatran or Warfarin

Background and Purpose— In randomized trials, patients with atrial fibrillation (AF) receiving dabigatran, a direct oral anticoagulant, had lower risk of intracranial bleeding (ICB) than those on warfarin. However, concerns exist about potential worse outcomes in dabigatran users if bleeding occurs, given the lack of approved reversal agents. Thus, we examined in-hospital mortality in AF patients with ICB being treated with dabigatran versus warfarin in a real-world population in the United States. Methods— We analyzed healthcare utilization claims in the Truven Health Marketscan Research Databases. The study sample included patients with AF admitted to a hospital with a primary diagnosis of ICB. Information on medications, inpatient, and outpatient diagnoses was obtained from available claims. Propensity score–adjusted risk ratios and 95% confidence intervals of in-hospital mortality comparing current users of dabigatran versus warfarin were estimated using relative risk regression. Results— Among 2391 AF patients admitted with ICB (2290 on warfarin, 101 on dabigatran), 531 died during their admission. In-hospital mortality was similar in those treated with warfarin (22%) or dabigatran (20%). Compared with warfarin users, the propensity score–adjusted risk ratio (95% confidence interval) of mortality in dabigatran users was 0.93 (0.62–1.37). Associations were similar across different ICB subtypes (intracerebral hemorrhage, subarachnoid hemorrhage, and subdural hematoma). Conclusions— In this sample of AF patients with ICB on oral anticoagulants, dabigatran was not associated with higher in-hospital mortality compared with warfarin. Hence, reluctance to use dabigatran because of a lack of approved reversal agents is not supported by our results.
Identification of structural and molecular determinants of the tyrosine‐kinase Wzc and implications in capsular polysaccharide export

Capsular polysaccharides are well‐established virulence factors of pathogenic bacteria. Their biosynthesis and export are regulated within the transmembrane polysaccharide assembly machinery by the autophosphorylation of atypical tyrosine‐kinases, named BY‐kinases. However, the accurate functioning of these tyrosine‐kinases remains unknown. Here, we report the crystal structure of the non‐phosphorylated cytoplasmic domain of the tyrosine‐kinase Wzc from Escherichia coli in complex with ADP showing that it forms a ring‐shaped octamer. Mutational analysis demonstrates that a conserved EX2RX2R motif involved in subunit interactions is essential for polysaccharide export. We also elucidate the role of a putative internal regulatory tyrosine and we show that BY‐kinases from proteobacteria autophosphorylate on their C‐terminal tyrosine cluster via a single‐step intermolecular mechanism. This structure‐function analysis also allows us to demonstrate that two different parts of a conserved basic region called the RK‐cluster are essential for polysaccharide export and for kinase activity respectively. Based on these data, we revisit the dichotomy made between BY‐kinases from proteobacteria and firmicutes and we propose a unique process of oligomerization and phosphorylation. We also reassess the function of BY‐kinases in the capsular polysaccharide assembly machinery.
Prevalence of accessory head of flexor pollicis longus muscle and its relation to anterior interosseous nerve in Thai population

A detailed description of the accessory head of flexor pollicis longus muscle (AHFPL) in the Thai population has not been reported. Because it is one of the causes of anterior interosseous nerve syndrome (AINS), a study was carried out on 120 Thai cadavers (70 embalmed, 50 fresh; 78 male, 42 female) to elucidate the prevalence of AHFPL, its morphology and relationship with the anterior interosseous nerve (AIN). The prevalence of AHFPL was 62.1% (149/240) with 74.5% (111/149) of its origin on medial epicondyle, 23.5% (35/149) on coronoid process and 2% (3/149) on flexor digitorum superficialis muscle. One hundred percent of its insertion was on the ulnar border of flexor pollicis longus tendon, and it was 98% (146/149) fusiform‐shaped and 2% (3/149) slender shaped, with a diameter between 0.8–16.0 mm (average 6.7 mm), averaging 6.5 mm on the right and 4.2 mm on the left. The right was significantly statistically larger than the left (P < 0.05). The average distance from the mid‐point of the distal wrist crease to the insertion point of AHFPL was 12.8 cm. Four patterns of relationship with AIN were noted including: 1) I AIN passed anterior to AHFPL, 13.4% (20/149); 2) AIN passed lateral to AHFPL, 65.8% (98/149); 3) AIN passed posterior to AHFPL, 8.1% (12/149); and 4) AIN passed both lateral and posterior to AHFPL, 12.8% (19/149). We believe that the latter two patterns (3 and 4) with AIN passing posteriorly would be more likely to be associated with AINS due to anatomic considerations. Clin. Anat. 17:631–635, 2004. © 2004 Wiley‐Liss, Inc.
Pentosan polysulfate sodium therapy for men with chronic pelvic pain syndrome: a multicenter, randomized, placebo controlled study.

PURPOSE We evaluated the efficacy and tolerability of pentosan polysulfate sodium (PPS) for the treatment of men with chronic pelvic pain syndrome (CPPS), National Institutes of Health (NIH) category III. MATERIALS AND METHODS In a 16-week double-blind study 100 men with a clinical diagnosis of CPPS were randomized to receive 300 mg PPS or placebo 3 times daily. Clinical Global Improvement (CGI) was the primary outcome measure. Additional outcome measures were the NIH-Chronic Prostatitis Symptom Index (CPSI), Subjective Global Assessment and Symptom Severity Index assessment tools. RESULTS Significantly more patients receiving PPS experienced moderate to marked improvement based on CGI assessment (18 or 37% vs 8 or 18%, p = 0.04). However, mean CGI scores were not significantly different between the PPS group (1.0) and placebo groups (1.0 vs 0.6, p = 0.107). All NIH-CPSI domains suggested a positive effect for PPS and for total NIH-CPSI the difference approached statistical significance (-5.9 or 22% vs -3.2 or 12%, p = 0.068). The PPS group showed significantly greater improvement in NIH-CPSI quality of life domain scores than the placebo group (-2.0 or 22% vs -1.0 or 12%, p = 0.031). Of patients receiving PPS 67% and 80% of those receiving placebo completed the 16-week study. Diarrhea, nausea and headache were the most common adverse events. CONCLUSIONS Pentosan polysulfate (900 mg daily) was more likely than placebo to provide relief for CPPS symptoms.
Early MRI measures independently predict 1-year and 2-year radiographic progression in rheumatoid arthritis: secondary analysis from a large clinical trial

Objective To determine if early MRI measures predict X-ray progression at 1 and 2 years in a large RA trial cohort. Design This study included 256 methotrexate (MTX)-naïve RA patients from a randomised placebo-controlled trial of golimumab (GO-BEFORE). MRIs of wrist and 2nd–5th metacarpophalangeal joints at 0, 12, 24, 52 and 104 weeks were obtained and scored using the RAMRIS system. Multivariable logistic regression examined if baseline and early change (weeks 12/24) in RAMRIS scores independently predicted progression of the van der Heijde-Sharp (vdHS) score and MRI erosion score at 1 and 2 years of follow-up. Results High baseline score and poor improvement over the first 24 weeks in synovitis (p=0.003 and p=0.003, respectively) and in bone oedema (p=0.02 and p=0.001, respectively) were independent predictors of X-ray progression at 1 year. Associations were significant or tended towards an association at 2 years. An increase in RAMRIS bone erosion >0.5 at weeks 12 and 24 also predicted X-ray progression (p<0.003). Poor 12-week improvement in bone oedema was associated with X-ray and MRI progression at 1 year (p<0.05). Regression models that incorporated baseline and 12-week and 24-week changes in MRI measures of synovitis (AUC=0.71) and bone oedema (AUC=0.70) improved the prediction of X-ray progression at 1 year above clinical disease activity alone (AUC=0.66, p<0.04). Conclusions Baseline and early changes in MRI measures independently predicted X-ray and MRI progression at later time-points. The predictive validity established here supports potential use in shorter-duration studies to determine efficacy of RA therapies in preventing structural damage.