Miracle-dz/UniFAR-FTUs huggingface dataset:
PavB is a surface‐exposed adhesin of Streptococcus pneumoniae contributing to nasopharyngeal colonization and airways infections

The genomic analysis of Streptococcus pneumoniae strains identified the Pneumococcal adherence and virulence factor B (PavB), whose repetitive sequences, designated Streptococcal Surface REpeats (SSURE), interact with human fibronectin. Here, we showed the gene in all tested pneumococci and identified that the observed differences in the molecular mass of PavB rely on the number of repeats, ranging from five to nine SSURE. PavB interacted with fibronectin and plasminogen in a dose‐dependent manner as shown by using various SSURE peptides. In addition, we identified PavB as colonization factor. Mice infected intranasally with ΔpavB pneumococci showed significantly increased survival times compared with wild‐type bacteria. Importantly, the pavB‐mutant showed a delay in transmigration to the lungs as observed in real‐time using bioluminescent pneumococci and decreased colonization rates in a nasopharyngeal carriage model. In co‐infection experiments the wild‐type out‐competed the pavB‐mutant and infections of epithelial cells demonstrated that PavB contributes to adherence to host cell. Blocking experiments suggested a function of PavB as adhesin, which was confirmed by direct binding of SSURE peptides to host cells. Finally, PavB may represent a new vaccine candidate as SSURE peptides reacted with human sera. Taken together, PavB is a surface‐exposed adhesin, which contributes to pneumococcal colonization and infections of the respiratory airways.
Accuracy of clinical prediction rules in peptic ulcer perforation: an observational study

Abstract Objective. The aim of the present study was to compare the ability of four clinical prediction rules to predict adverse outcome in perforated peptic ulcer (PPU): the Boey score, the American Society of Anesthesiologists (ASA) score, the Acute Physiology and Chronic Health Evaluation (APACHE) II score, and the sepsis score. Material and methods. Design: an observational multicenter study. Participants and settings: a total of 117 patients surgically treated for PPU between 1 January 2008 and 31 December 2009 in seven gastrointestinal departments in Denmark were included. Pregnant and breastfeeding women, non-surgically treated patients, patients with malignant ulcers, and patients with perforation of other organs were excluded. Primary outcome measure: 30-day mortality rate. Statistical analysis: the ability of four clinical prediction rules to distinguish survivors from non-survivors (discrimination ability) was evaluated by the area under the receiver operating characteristic curve (AUC), positive predictive values (PPVs), negative predictive values (NPVs), and adjusted relative risks. Results. Median age (range) was 70 years (25–92 years), 51% of the patients were females, and 73% of the patients had at least one co-existing disease. The 30-day mortality proportion was 17% (20/117). The AUCs: the Boey score, 0.63; the sepsis score, 0.69; the ASA score, 0.73; and the APACHE II score, 0.76. Overall, the PPVs of all four prediction rules were low and the NPVs high. Conclusions. The Boey score, the ASA score, the APACHE II score, and the sepsis score predict mortality poorly in patients with PPU.
Topographical relationships between arcuate fasciculus connectivity and cortical thickness

The arcuate fasciculus (AF) connects cortical regions important in language processing, but how fiber coherence and organization relates to gray matter macrostructure remains uncharacterized. We used high‐resolution structural and 30‐direction diffusion imaging data from 36 healthy adults (24 male/12 female; mean age, 30.5 ± 9.8 years) to establish the relationships between AF microstructure and regional variations in cortical gray matter within language networks. Cortical pattern‐matching algorithms were used to measure gray matter thickness at high‐spatial density, and a validated diffusion tractography method was used to reconstruct the AF in the left and right hemisphere of each subject. Relationships between imaging measures and neuropsychological scores of verbal fluency were additionally assessed. Results revealed positive and highly topographical associations between arcuate fractional anisotropy (FA) and cortical thickness within anterior and posterior language regions and surrounding cortices, more prominently in the left hemisphere. These regional cortical thickness/FA relationships were primarily attributable to variations in radial diffusivity. Associations between cortical thickness and verbal fluency were observed in perisylvian language‐related regions. Language scores were associated with left‐hemisphere AF axial diffusivity, but not with AF FA or radial diffusivity. These findings thus suggest that particular components of white matter microstructure and regional increases in cortical thickness benefit aspects of language processing. Furthermore, the topographical relationships between independent measures of white matter and gray matter integrity suggest that rich developmental or environmental interactions influence brain structure and function where the presence and strength of such associations may elucidate pathophysiological processes influencing language systems. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.
Peripheral cholangiocarcinoma (cholangiocellular carcinoma): Clinical features, diagnosis and treatment

Peripheral cholangiocarcinoma is a relatively rare cancer. However, it is known to have an unfavourable prognosis compared with that of hepatocellular carcinoma. Little is known about its aetiology, clinical or pathological features. Recently, with the development of imaging modalities, early staged cholangiocarcinoma has been diagnosed with relative ease. Surgery is the optimal therapy. Total hepatectomy does not provide survival benefit. Conventional surgery remains the only effective treatment, even for patients with advanced‐stage tumours. Factors influencing survival after hepatectomy were tumour‐free margin, lymphnodes metastasis and histopathology of tumour. Palliative intrahepatic tubing or percutaneous transhepatic biliary drainage and brachytherapy can alleviate jaundice and cholangitis, thereby prolonging survival in some cases.
Connexin 43 Delimits Functional Domains of Neurogenic Precursors in the Spinal Cord

The cells lining the central canal (CC) of the spinal cord derive from the ventral part of the neural tube and, in some vertebrates, are responsible for the functional recovery after spinal cord injury. The region that surrounds the CC in the turtle contains proliferating cells that seem to generate both glia and neurons. Understanding the biology of spinal progenitors with the potential to generate new neurons “in situ” is important for cell replacement therapies. Here, we aimed to identify and characterize precursor cells in the spinal cord of Trachemys dorbignyi. To evaluate the population of proliferating cells, 5-bromo-2′-deoxyuridine (BrdU) was injected every 4 h (50 μg/g, i.p.) during 24 h. We found BrdU+ nuclei around the CC with a higher density in the lateral quadrants, in which whole-cell patch-clamp recordings showed extensive dye coupling of cells. Carbenoxolone (100 μm) increased the input resistance, suggesting strong gap junction coupling among precursors. The expression of brain lipid binding protein (a marker of a subtype of radial glia) and Pax6 matched the location of clusters, suggesting these cells belonged to a domain of neurogenic precursors. These domains were delimited by a high density of connexin 43 (Cx43) located on the endfeet of CC contacting cells. Our findings indicate that spinal precursors share basic properties with those in the embryo and neurogenic niches of the adult brain, and support a key role of functional clustering via Cx43 in spinal cord neurogenesis.
Synaptic AMPA receptor subunit trafficking is independent of the C terminus in the GluR2-lacking mouse

Glutamate is the primary excitatory neurotransmitter in the brain, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type glutamate receptors mediate most fast synaptic transmission. AMPA receptors are tetrameric assemblies composed from four possible subunits (GluR1–4). In hippocampal pyramidal cells, AMPA receptors are heteromeric receptors containing the GluR2 subunit and either GluR1 or GluR3. It is generally accepted that the trafficking of GluR1/GluR2 receptors to synapses requires activity, whereas GluR2/GluR3 receptors traffic constitutively. It has been suggested that the trafficking is governed by the cytoplasmic C termini of the subunits. Because the basis for this theory relied on the introduction of unnatural, homomeric, calcium-permeable AMPA receptors, we have used the GluR2−/− knock out mouse to determine whether the expression of mutated forms of GluR2 can rescue WT synaptic responses. We find that GluR2, lacking its entire C terminus, or a GluR2 chimera containing the C terminus of GluR1, is capable of trafficking to the synapse in the absence of activity. These findings suggest that the GluR2 C terminus is not required for GluR2 synaptic insertion.
C331A Mutant of Neuronal Nitric-oxide Synthase Is Labilized for Hsp70/CHIP (C Terminus of HSC70-interacting Protein)-dependent Ubiquitination*

It is established that suicide inactivation of neuronal nitric-oxide synthase (nNOS) by drugs and other xenobiotics leads to ubiquitination and proteasomal degradation of the enzyme. The exact mechanism is not known, although it is widely thought that the covalent alteration of the active site during inactivation triggers the degradation. A mechanism that involves recognition of the altered nNOS by Hsp70 and its cochaperone CHIP, an E3-ubiquitin ligase, has been proposed. To further address how alterations of the active site trigger ubiquitination of nNOS, we examined a C331A nNOS mutant, which was reported to have impaired ability to bind l-arginine and tetrahydrobiopterin. We show here that C331A nNOS is highly susceptible to ubiquitination by a purified system containing ubiquitinating enzymes and chaperones, by the endogenous ubiquitinating system in reticulocyte lysate fraction II, and by intact HEK293 cells. The involvement of the altered heme cleft in regulating ubiquitination is confirmed by the finding that the slowly reversible inhibitor of nNOS, NG-nitro-l-arginine, but not its inactive d-isomer, protects the C331A nNOS from ubiquitination in all these experimental systems. We also show that both Hsp70 and CHIP play a major role in the ubiquitination of C331A nNOS, although Hsp90 protects from ubiquitination. Thus, these studies further strengthen the link between the mobility of the substrate-binding cleft and chaperone-dependent ubiquitination of nNOS. These results support a general model of chaperone-mediated protein quality control and lead to a novel mechanism for substrate stabilization based on nNOS interaction with the chaperone machinery.
The Generalized Quantum Episodic Memory Model

Recent evidence suggests that experienced events are often mapped to too many episodic states, including those that are logically or experimentally incompatible with one another. For example, episodic over-distribution patterns show that the probability of accepting an item under different mutually exclusive conditions violates the disjunction rule. A related example, called subadditivity, occurs when the probability of accepting an item under mutually exclusive and exhaustive instruction conditions sums to a number >1. Both the over-distribution effect and subadditivity have been widely observed in item and source-memory paradigms. These phenomena are difficult to explain using standard memory frameworks, such as signal-detection theory. A dual-trace model called the over-distribution (OD) model (Brainerd & Reyna, 2008) can explain the episodic over-distribution effect, but not subadditivity. Our goal is to develop a model that can explain both effects. In this paper, we propose the Generalized Quantum Episodic Memory (GQEM) model, which extends the Quantum Episodic Memory (QEM) model developed by Brainerd, Wang, and Reyna (2013). We test GQEM by comparing it to the OD model using data from a novel item-memory experiment and a previously published source-memory experiment (Kellen, Singmann, & Klauer, 2014) examining the over-distribution effect. Using the best-fit parameters from the over-distribution experiments, we conclude by showing that the GQEM model can also account for subadditivity. Overall these results add to a growing body of evidence suggesting that quantum probability theory is a valuable tool in modeling recognition memory.
Analysis of immune reconstitution after autologous CD34+ stem/progenitor cell transplantation for systemic sclerosis: predominant reconstitution of Th1 CD4+ T cells.

OBJECTIVE The aim of this study is to evaluate the mechanism of long-term effect of autologous haematopoietic stem cell transplantation (ASCT) in treatment of SSc. METHODS Eleven patients (three males and eight females) with SSc were enrolled. Blood mononuclear cells were harvested after mobilization treatment with CYC and G-CSF. CD34+ haematopoietic stem/progenitor cell fractions were purified and cryopreserved. Patients were transplanted with > 2 × 10(6)/kg autologous CD34+ cells after high-dose CYC (50 mg/kg for 4 days) conditioning. Immune reconstitution was evaluated serially by analysing lymphocyte subpopulations for 36 months. RESULTS Progressive improvement of skin sclerosis has been observed for 3 years in most of the patients. The serum level of anti-Scl-70, an auto-antibody specific to SSc, was progressively decreased after ASCT. Improvement of skin sclerosis was significantly associated with the change in the serum anti-Scl-70 level after ASCT at 36 months. Serum levels of KL-6 and surfactant protein D, indicators for interstitial pneumonia activity, were also significantly decreased. The number of CD8+ T cells immediately recovered within a month after ASCT, while the number of CD4+ T cells remained low for >36 months post-transplant. The majority of CD4+ cells were memory but not naïve T cells, and regulatory CD4+ T cells were not recovered. Th1/Th2 ratio was significantly increased after ASCT. CONCLUSIONS ASCT with purified CD34+ cells was effective in controlling the disease activity of SSc. Th1/Th2 ratio was significantly increased for at least 3 years after ASCT.
Clinical and pathophysiological significance of anti-neutrophil cytoplasmic autoantibodies in vasculitis syndromes

Necrotizing vasculitis of small blood vessels is a rare condition, but when it affects important organs it can lead to life-threatening organ damage and death. Thus, recognizing these conditions at an early stage before they spread to become systemic is a constant challenge to clinical medicine. The objectives of this review are: to give advice on clinical indications for ANCA diagnostics and laboratory procedures for highly specifically detecting the most important ANCA; to provide some data on the autoantigens involved in ANCA reactivity in small vessel vasculitides; and to discuss at the occurrence of ANCA in different vasculitic populations and at different stages of disease. One important task for the near future will be to standardize the assays used for ANCA detection/quantification and to harmonize the results given to clinicians by ensuring that international reference reagents are used by laboratories and the diagnostic industry. Finally, the author has attempted to summarize the role that ANCA are currently believed to play in the immuno-inflammatory events that take place in tissues and that affect small vessels in idiopathic vasculitis. The review concludes that the presence of ANCA is likely to become an important criterion for diagnosing idiopathic small vessel vasculitis.
Assessment of safety of the major antimalarial drugs

Antimalarial drugs remain the major intervention tool for the global malaria control efforts that save millions of lives. Nonetheless, emergence and spread of Plasmodium parasites resistant against chloroquine and other major antimalarial drugs has brought the urgency to develop a new generation of safe and effective drugs against malaria. In this article, the safety data for major antimalarial drugs is reviewed. Although an ample amount of clinical data regarding the safety and tolerability of several of these drugs in older children and adults is available, more critical safety and tolerability studies in pregnant women and young children is desirable. To offset the partial loss in efficacy due to drug resistance in malaria parasites acquired against specific drugs, treatment regimens often rely upon the combination of two or more drugs. However, combination therapy requires additional safety, toxicity and tolerability studies in all population groups where these drugs are administered. A uniform standard in assessing the safety and tolerability of antimalarial drugs will be useful in the formulation and implementation of malaria treatment policies that are based on the drug effectiveness, safety and tolerability.
Inhibitory effects of sucrose fatty acid esters on survival of Yersinia enterocolitica on eggshell surface and use of blue lake as indicator of bacterial penetration into eggs

Aims: To determine the effectiveness of sucrose monolaurate (SML) and sucrose monocaprate (SMC), alone and in combination with ethylenediaminetetraacetic acid (EDTA), propionic acid (PA) or citric acid (CA) in reducing mesophilic aerobic bacteria (MAB) and Yersinia enterocolitica O:9 populations on eggshells and their damage potential on the microstructure of shell cuticle.
Genetic conflict and conditional altruism in social aphid colonies

Although kin selection is central to the modern study of social evolution, recent studies of social species have revealed that no simple relationship exists between levels of kinship and sociality. The soldier-producing aphids are unique among highly social animals because, barring movement by aphids between colonies, they occur in clonal groups of genetically identical individuals. Potentially, clonality simplifies efforts to understand social evolution in aphids by obviating issues of intragroup conflict. However, we report here high levels of clonal mixing and conflict in an aphid society. The gall-dwelling colonies of a social aphid species (Pemphigus obesinymphae) are not pure clones, but are invaded by large numbers of aphids from other clones. Intruders behave and develop selfishly once they have invaded a colony of nonkin. They refrain from risky defensive behaviors and accelerate their own development into reproductive rather than defensive stages. This conditionality in the social life of P. obesinymphae reveals complex dynamics and a degree of behavioral plasticity not previously known in aphid societies.
A transformation-driven approach for recognizing textual entailment†

Abstract Textual Entailment is a directional relation between two text fragments. The relation holds whenever the truth of one text fragment, called Hypothesis (H), follows from another text fragment, called Text (T). Up until now, using machine learning approaches for recognizing textual entailment has been hampered by the limited availability of data. We present an approach based on syntactic transformations and machine learning techniques which is designed to fit well with a new type of available data sets that are larger but less complex than data sets used in the past. The transformations are not predefined, but calculated from the data sets, and then used as features in a supervised learning classifier. The method has been evaluated using two data sets: the SICK data set and the EXCITEMENT English data set. While both data sets are of a larger order of magnitude than data sets such as RTE-3, they are also of lower levels of complexity, each in its own way. SICK consists of pairs created by applying a predefined set of syntactic and lexical rules to its T and H pairs, which can be accurately captured by our transformations. The EXCITEMENT English data contains short pieces of text that do not require a high degree of text understanding to be annotated. The resulting AdArte system is simple to understand and implement, but also effective when compared with other existing systems. AdArte has been made freely available with the EXCITEMENT Open Platform, an open source platform for textual inference.
Relation of optical coherence tomography to microanatomy in normal and rd chickens.

PURPOSE To elucidate the relation between optical coherence tomography (OCT) scans and retinal histology in normal and retinal degeneration (rd) chickens. METHODS Retinas from adult normal and rd chickens were examined in vivo with OCT at 850 nm and compared quantitatively with stained cryosections of unfixed retinas from the same locations. RESULTS The nerve fiber layer (NFL) and inner plexiform layer (IPL) show homogeneous backscatter throughout their thicknesses. NFL reflectivity is approximately 0.6 log units higher than that of the IPL. The inner nuclear layer shows a low reflectivity; the properties of reflections from ganglion cell and outer nuclear layers are indeterminate. The outer retina and choroid form a large reflective complex. Photoreceptor inner segments produce the highest of these reflections in normal chicken retinas, approximately 1.5 log units higher than that of the IPL. The retinal pigment epithelium also has a relatively large backscatter coefficient and is the dominant reflector in rd retinas that lack photoreceptors. Choroidal pigment produces an intermediate level of backscatter and is the largest attenuator of signal at 850 nm. CONCLUSIONS Quantified OCT signals have a predictable relationship to histology and pathology in chicken retinas. The results from rd retinas represent a first step toward in vivo quantitation of retinal structure in retinal degenerative disease.
The microvascular anastomotic coupler for venous anastomoses in free flap breast reconstruction improves outcomes.

BACKGROUND Venous couplers are ubiquitous around the world and are a useful tool for the reconstructive microsurgeon. A systematic review of coupler performance studies demonstrated a thrombosis rate range of 0% to 3%, whilst the average time of using the device is 5 minutes. There is sparse published data on cost analysis and the impact of operator experience on the anastomotic coupler device success. Improvements in outcomes other than time benefits have also not been shown. This study aims to address these deficiencies in the literature. METHODS A retrospective clinical study was undertaken, aiming to compare equivalent groups of patients that had free flap surgery with venous micro-anastomoses with those that had sutured anastomoses. The cohort comprised all patients undergoing microsurgical breast reconstruction at the St Andrew's Centre for Plastic Surgery & Burns from January 2009 to December 2014. RESULTS Between January 2010 to December 2014, 1,064 patients underwent 1,206 free flap breast reconstructions. The average age of patients was 50 years. Seventy percent of patients underwent mastectomy and immediate reconstruction during this period with the remaining 30% having a delayed reconstruction. The 1,206 free flaps comprised of 83 transverse myocutaneous gracilis (TMG) flaps, and 1,123 deep inferior epigastric artery perforator (DIEP) flaps. In total the coupler was used in 319 flaps, 26% of the cohort. There was a statistically significant clinical benefit in using the anastomotic coupler for venous anastomosis. Overall, the return to theatre rate was 12.69% whilst the overall flap loss rate was 0.75%. The overall coupler failure rate was significantly less at 1.4% whilst sutured vein failure rate was 3.57% (P=0.001). CONCLUSIONS The anastomotic coupler for venous anastomosis in free flap surgery is associated with reduced operating times, reduced take-backs to theatre and cost benefits. This is the first study to demonstrate clear clinical benefits to anastomotic couplers, and suggests that these may be the gold standard for venous microanastomosis. With increasing experience with their use and technological advances, these outcomes may continue to improve.