Miracle-dz/UniFAR-FTUs huggingface dataset:
MRP9, an unusual truncated member of the ABC transporter superfamily, is highly expressed in breast cancer

Combining a computer-based screening strategy and functional genomics, we previously identified MRP9 (ABCC12), a member of the ATP-binding cassette (ABC) superfamily. We now show that the gene has two major transcripts of 4.5 and 1.3 kb. In breast cancer, normal breast, and testis, the MRP9 gene transcript is 4.5 kb in size and encodes a 100-kDa protein. The protein is predicted to have 8 instead of 12 membrane-spanning regions. When compared with closely related ABC family members, it lacks transmembrane domains 3, 4, 11, and 12 and the second nucleotide-binding domain. In other tissues including brain, skeletal muscle, and ovary, the transcript size is 1.3 kb. This smaller transcript encodes a nucleotide-binding protein of ≈25 kDa in size. An in situ hybridization study shows that the 4.5-kb transcript is expressed in the epithelial cells of breast cancer. An antipeptide antibody designed to react with the amino terminus of the protein detects a 100-kDa protein in testis and the membrane fraction of a breast cancer cell line. Because the 4.5-kb RNA is highly expressed in breast cancer and not expressed at detectable levels in essential normal tissues, MRP9 could be a useful target for the immunotherapy of breast cancer. Because of the unusual topology of the two variants of MRP9, we speculate that they may have a different function from other family members.
Mortality and Incidence of Atrial Fibrillation in Paced Patients

Mortality and AF Incidence in Paced Patients. This review presents and discusses available data from randomized controlled trials on the prognosis of pacemaker patients, especially the incidences of atrial fibrillation (AF) and death, the impact of pacing mode selection, and the impact of AF on prognosis. The incidence of AF is several times higher in paced patients than in the nonpaced population. The annual incidences of AF and chronic AF are at least 5% and 3%, respectively, after pacemaker implantation. Mean lifetime cumulative incidences of AF and chronic AF can be estimated at approximately 30% to 40% and 20%, respectively. The most important predictors of AF are brady‐tachy syndrome, sick sinus syndrome, and selection of VVI(R) pacing mode. The expected lifespan in paced patients is shorter than in the age‐matched nonpaced population. One of the factors decreasing lifespan in paced patients most likely is the high incidence and prevalence of AF. In patients with sick sinus syndrome, VVI pacing significantly increases AF and mortality compared with AAI pacing. In a mixed population of patients with bradycardia, DDD(R) pacing causes AF less often than does VVI(R) pacing. Survival does not differ between these pacing modes within the first 3.5 years after pacemaker implantation. At the present time, AAI(R) should be the preferred pacing mode in patients with sick sinus syndrome, and DDD(R) should be used for other patients without chronic AF for prevention of AF. It is not clear whether prevention of AF will improve survival of paced patients.
[The effect of proton pump inhibitor on healing of post-esophageal variceal ligation ulcers].

BACKGROUND/AIMS Esophageal variceal ligation (EVL) is the most preferable method for controlling variceal bleeding. However, EVL is associated with complications such as hemorrhage, chest pain, dysphagia, and odynophagia due to post-EVL ulcers in the esophageal mucosa. The aim of this study was to assess the effect of proton pump inhibitor (PPI), pantoprazole on the healing of post-EVL ulcers. METHODS Forty seven patients were randomly allocated into PPI group and control group. Patients in PPI group received 40 mg of pantoprazole intravenously for 3 days after EVL, then 40 mg of oral pantoprazole for 11 days consecutively. Control patients received intravenous and oral placebo. Endoscopic examinations were performed twice at 7+/-2 days and 14+/-2 days after EVL respectively. Clinical outcomes include the size of ulcers, symptoms reported by patients; chest pain, dysphagia, and odynophagia. RESULTS Forty seven patients completed the 7 days protocol (PPI/control; 25/22), and twenty six patients completed the 14 days protocol (PPI/control; 16/10). Post-EVL ulcers in PPI group were significantly smaller than those in control group (7 days; 98.7 mm2/119.4 m2, 14 days; 32.3 m2/43.8 m2, p<0.01). No difference was observed between two the groups with respect to summations of symptom scores (p> 0.05). Nineteen patients (PPI/control; 9/10) did not complete the 14 days protocol due to patients' refusal and adverse outcomes, such as hepatic failure and sepsis with bleeding from post-EVL ulcer occurred in two patients of control group. CONCLUSIONS PPI treatment following EVL may be effective in healing post-EVL ulcer.
Evidence–Based Medicine and Regulatory Oversight

It is no secret that our country is in the midst of an opioid crisis. With hundreds of Americans dying everyday due to opioid use, it is hard to ignore. Closely related, though not as often talked about, is another crisis providers are facing: chronic pain and its treatment. The treatment approach to this problem is multifaceted. Evidence-based studies are the hallmark of appropriate treatment; however, increasing patient concerns and regulatory oversight have added an additional layer that physicians and other prescribers have to incorporate. Navigating a balance between evidence-based treatment, regulatory pressures, and patient concerns is now at the forefront of pain management and patient care.
Impact of left atrial fibrosis and left atrial size on the outcome of catheter ablation for atrial fibrillation

Background Left atrial (LA) dilatation is an important risk factor for recurrence of atrial fibrillation (AF) after radiofrequency catheter ablation (RFCA). However, the clinical applications to select patients eligible for RFCA according to LA size is limited. Additional pre-procedural assessment of LA fibrosis might improve patient selection for RFCA. Objective To investigate the impact of LA size and LA fibrosis on the outcome of RFCA for AF. Methods One hundred and seventy consecutive patients undergoing RFCA for AF were studied. LA size was assessed by measuring maximum LA volume index on echocardiography. LA wall ultrasound reflectivity was assessed by measuring echocardiography-derived calibrated integrated backscatter (IBS) as a surrogate of LA fibrosis. Results After 12±3 months' follow-up, 103 patients (61%) had maintained sinus rhythm and 67 patients (39%) had recurrence of AF. Univariate Cox analyses identified LA wall ultrasound reflectivity, as well as LA size and type of AF, as predictors of AF recurrence after RFCA. Importantly, multivariate analyses showed that LA wall ultrasound reflectivity remained a strong predictor after correction for LA size and type of AF. Moreover, LA wall ultrasound reflectivity provided an incremental value in predicting outcome of RFCA over LA size and type of AF (increment in global χ2=61.6, p<0.001). Conclusion Assessment of LA fibrosis using two-dimensional echocardiography-derived calibrated IBS can be useful to predict AF recurrence after RFCA. Combined assessment of LA wall ultrasound reflectivity and LA size improves the identification of patients with a high likelihood for a successful ablation.
Measuring multi-dimensional, time-dependent mechanical properties of a human tibial fracture using an automated system

Abstract This paper presents an element of a long-term research project determining a clinically quantifiable end point for fracture healing in humans. An automated loading and measurement device is presented. It has been developed as a research tool for the assessment of the mechanical properties of a healing human tibial fracture. The device has been specifically designed for use with patients treated with external fixation. The characteristics of the device have been presented together with an assessment of errors. A typical sample of results has been presented to demonstrate the significance of the device; subsequent papers will examine the whole data set in greater depth. The results presented here confirm the non-linear behaviour of callus and reinforce the requirement to measure the load rate when measuring the fracture stiffness. A new material property for the assessment of fracture healing, namely γ, is examined and preliminary results are shown. Polar plots of stiffness demonstrate that, when measuring fracture stiffness, not only should the load rate be considered, but also the orientation of measurement. The results from this work support the view that the fracture stiffness should be measured in at least two planes. Currently a fracture can be considered healed when the fracture stiffness exceeds 15 N m/deg; this paper questions whether this value is now valid and suggests that it should be re-examined.
Mosquito-borne arboviruses in Norway: further isolations and detection of antibodies to California encephalitis viruses in human, sheep and wildlife sera

SUMMARY Seven virus strains antigenically related to the California encephalitis (CE) virus group were isolated from Norwegian Aedes spp. mosquitoes collected in 1976. So far CE viruses have been isolated from five different Aedes spp. in Norway. Furthermore, two virus strains related to the Bunyamwera group were isolated from Anopheles claviger. Antibodies to CE viruses were demonstrated in 22% of 1014 military recruits tested. Among 91 soldiers who were monitored by monthly blood samples during the mosquito season, seroconversions were detected in 11 individuals. Specific IgM antibodies were found in seven of them. Disease symptoms in connexion with the CE virus infections were not seen. The prevalence of CE antibodies in patients with CNS or respiratory infections was not higher than in control groups. Seroconversions were not seen in any of the groups. Screening of sheep sera from six different areas in northern Norway indicated significantly different degrees of CE virus activity. Passerine birds may be important CE virus hosts, while small rodents seem unimportant. Specific IgM antibodies were detected in the sera of one of three hares and one of two squirrels. Of the methods used, single radial haemolysis (SRH) and immuno-electroosmophoresis (IEOP) seemed to be well suited for serological screenings. However, an indirect immunofluorescence antibody test (IFAT) which was used may be an attractive alternative if high-quality anti-species conjugates are available. The haemagglutination-inhibition (HI) test used gave a high number of false positive results.
Camera-captured document image perspective distortion correction using vanishing point detection based on Radon transform

A correction method for perspective distortions on document images is discussed. In documents, lines and line feeds give rise to many horizontal and vertical lines, then two vanishing points generated by these lines can be computed. High-energy regions are identified in the Radon transform thanks to a binarization step. Then, the image is zero-padded and the inverse Radon transform is applied to underline the main lines direction in the original image. The distortion is corrected by the perspective mapping determined with the two vanishing points and we propose to compute the homography matrix for the perspective mapping. Experimental results show that our method can correct the perspective distortions effectively and outperforms the state-of-the-art for vanishing points detection accuracy.
Control of Leaf Expansion by Nitrogen Nutrition in Sunflower Plants' ROLE OF HYDRAULIC CONDUCTIVITY TURGOR

Nitrogen nutrition strongly affected the growth rate of young sunflower (Helianthus annuus L.) leaves. When plants were grown from seed on either of two levels of N availability, a 33% decrease in tissue N of expanding leaves was associated with a 75% overall inhibition of leaf growth. Almost all of the growth inhibition resulted from a depression of the daytime growth rate. Measurements of pressure-induced water flux through roots showed that N deficiency decreased root hydraulic conductivity by about half. Thus, N deficiency lowered the steady-state water potential of ex- panding leaves during the daytime when transpiration was occurring. As a result, N-deficient leaves were unable to maintain adequate turgor for growth in the daytime. N deficiency also decreased the hydraulic conductivity for water movement into expanding leaf cells in the absence of transpiration, but growth inhibition at night was much less than in the daytime. N nutrition had no detectable effects on plastic extensibility or the threshold turgor for growth.
pH-independent murine leukemia virus ecotropic envelope-mediated cell fusion: implications for the role of the R peptide and p12E TM in viral entry

Murine leukemia virus ecotropic and amphotropic envelope expression vectors were genetically engineered to generate truncations of the p15E TM cytoplasmic tail. The ecotropic construct CEET has the entire cytoplasmic tail of TM deleted, while the CEETR construct has only the R peptide portion of the tail deleted, thereby producing a TM subunit (p12E) that is identical to the one found in mature virions. The analogous amphotropic constructs were called CAET and CAETR. These envelopes, as opposed to their p15E TM counterparts, mediate cell-to-cell fusion at neutral pH in both transformed and nontransformed cell lines. Though the TM cytoplasmic domain is not required, its presence appears to augment such cell-to-cell fusion. This envelope-dependent fusion requires the presence of the viral receptor on the cell surface. Ecotropic virions bearing the p12E TM contain wild-type levels of the envelope complex and have near-normal titers. In contrast, virions which lack the cytoplasmic domain of TM (e.g., CEET) have 10- to 100-fold-lower titers but contain normal amounts of envelope. Both of the corresponding amphotropic virions contain normal amounts of envelope but have 10- to 100-fold-lower titers. Using immunofluorescent detection of envelope to monitor the fate of receptor-bound virions, we found that ecotropic murine leukemia virus envelope disappears from the cell surface while amphotropic envelope persists on the cell surface after virus binding. This pattern of immunofluorescence is consistent with the proposed routes of cell entry for these viruses, i.e., by endocytosis and direct fusion, respectively. In this assay, ecotropic virions bearing the genetically engineered p12E TM also appear to be internalized despite the ability of their envelope to mediate fusion at neutral pH in the same target cells. Our results show that direct fusion at neutral pH is a natural consequence of the surface expression of the mature ecotropic envelope and its receptor. We propose that the processing of the R peptide from the envelope TM (p15E) to yield p12E, at the time of virus budding or within virions, renders the envelope competent to fuse.
Hyperhomocysteinemia in Children Treated with Antiepileptic Drugs Is Normalized by Folic Acid Supplementation

Summary: Purpose: To assess the prevalence of hyperhomocysteinemia in pediatric patients treated with antiepileptic drugs (AEDs) and to evaluate the effect of folic acid supplementation on plasma total homocysteine (tHcy) concentrations in hyperhomocysteinemic patients.
Pharmacoepidemiological Approach to the Predisposing Factors for Highly Active Antiretroviral Therapy Failure in an Hiv-Positive Cohort from Cordoba City (Argentina) 1995–2005

Highly active antiretroviral therapy (HAART) restores immunity, avoids resistance and delays disease progression. Nonetheless, adverse medicament reactions (AMRs) and therapeutic failure (TF) are still deleterious events. Consequently, their predisposing factors should be evaluated. Data from 181 men and 28 women of an Argentinean cohort (1995–2005) were collected and analysed by logistic regression, studying 63 schemes (15 active principles). The AMRs were the main cause of scheme change, followed by TF and medicament simplification, without influence of age and sex. Twenty-nine schemes exhibited TF at least once. Compared with zidovudine–lamivudine–nevirapine (success: >75%), the following schemes fail more frequently (P < 0.01): pre-HAART (8-fold), indinavir-containing ones (30-fold) and retrotranscriptase inhibitors with ≥3 protease inhibitors (11-fold). Inadequate patient adherence preceded failure (>95%), but not successful treatments, with a strong AMR–TF association (P < 0.005). Although some schemes had inherently increased TF, low adherence, drug toxicity and TF were critically interrelated, interfering with HAART goals.
A New Iron-oxidizing/O2-reducing Supercomplex Spanning Both Inner and Outer Membranes, Isolated from the Extreme Acidophile Acidithiobacillus ferrooxidans*

The iron respiratory chain of the acidophilic bacterium Acidithiobacillus ferrooxidans involves various metalloenzymes. Here we demonstrate that the oxygen reduction pathway from ferrous iron (named downhill pathway) is organized as a supercomplex constituted of proteins located in the outer and inner membranes as well as in the periplasm. For the first time, the outer membrane-bound cytochrome c Cyc2 was purified, and we showed that it is responsible for iron oxidation and determined that its redox potential is the highest measured to date for a cytochrome c. The organization of metalloproteins inside the supramolecular structure was specified by protein-protein interaction experiments. The isolated complex spanning the two membranes had iron oxidase as well as oxygen reductase activities, indicating functional electron transfer between the first iron electron acceptor, Cyc2, and the CuA center of cytochrome c oxidase aa3. This is the first characterization of a respirasome from an acidophilic bacterium. In Acidithiobacillus ferrooxidans,O2 reduction from ferrous iron must be coupled to the energy-consuming reduction of NAD+(P) from ferrous iron (uphill pathway) required for CO2 fixation and other anabolic processes. Besides the proteins involved in the O2 reduction, there were additional proteins in the supercomplex, involved in uphill pathway (bc complex and cytochrome Cyc42), suggesting a possible physical link between these two pathways.
Tissue‐specific expression of type XII collagen during mouse embryonic development

Polyclonal antibodies were raised in rabbits against a fusion peptide representing a portion of the amino‐terminal non‐triplehelical domain of mouse type XII collagen. The antibodies reacted with bands of 220 and 350 kDa on Western blots of mouse tissue extracts. Immunohistochemical analyses of mouse embryos demonstrated that type XII collagen is expressed mainly in dense connective tissues of tendons, ligaments, dermis, cornea, blood vessel walls, meninges, and developing membranous bones. Comparison of skin extracts and medium of cultured mouse skin fibroblasts by Western blotting showed that while tissues contain short 220 kDa type XII collagen polypeptides as well as the long form, cultured cells produce mainly the long form with 350 kDa polypeptides. © 1993 wiley‐Liss, Inc.
A candidate gene association study of alcohol consumption in young women.

BACKGROUND Excessive alcohol consumption contributes to significant morbidity and mortality. Heritable influences contribute to 50% of the variation in alcohol consumption, suggesting the important role of genes. We used data on a previously defined alcohol consumption factor score in a sample of 827 young women to investigate association with 1,014 single-nucleotide polymorphisms in genes related to addiction. METHODS Data were drawn from the Missouri Adolescent Female Twin Study (MOAFTS) with replication in the college drinking sample (CDS). Genotypic and phenotypic data were available on 827 MOAFTS and 100 CDS women of European-American ancestry. Data on 1,014 single-nucleotide polymorphisms (SNPs) across 130 genes related to addiction were utilized. Association was conducted in QTDT, which allows for identity-by-descent information to account accurately for twin status in the analysis. The total association variance components model was used, with specification of variance components for relatedness in MOAFTS. RESULTS The top signals included clusters of SNPs in tryptophan hydroxylase 2 (TPH2) (e.g., rs1386496, p = 0.0003) and dopa decarboxylase (DDC) (e.g., rs3779084, p = 0.0008), genes that encode proteins responsible for serotonin synthesis. Additional polymorphisms in ADH1B, ADH1C, ADH7, and ADH1A1 were also associated at p < 0.05. The false discovery rate for the top signal (p = 0.0003) was 0.15, suggesting nominal significance only. Replication was limited and noted for 2 SNPs in ADH1C. CONCLUSIONS While no results survive the burden of multiple testing, nominal findings in TPH2 and DDC suggest the potential role of the serotonin synthesis pathway in alcohol consumption.
Cathelicidin as a link between sarcoidosis and tuberculosis.

SETTING Sarcoidosis and tuberculosis share notable clinical, radiological, histological, and immunological similarities. The importance of vitamin D has long been investigated in these two granulomatous lung diseases. Cathelicidin is an antimicrobial peptide of the innate immune system, directly induced by vitD3. OBJECTIVE To evaluate the role of cathelicidin in sarcoidosis and tuberculosis development. DESIGN The study included 30 consecutive patients with active lung tuberculosis, 30 patients with sarcoidosis, and 20 healthy controls. 25-hydroxyvitamin D [25(OH)D] and cathelicidin levels were measured in blood samples. RESULTS Vitamin D levels were significantly higher (p<0.001) in tuberculosis patients (22.5 ± 9.96 ng/ml) than in sarcoidosis patients (11.75 ± 8.92 ng/ml). Severe vitamin D deficiency was as frequent as 47% in sarcoidosis patients compared to only 3% in tuberculosis patients. Cathelicidin levels were significantly higher in the control group (120.37 ± 41.03 pg/ml) than in sarcoidosis (67.68 ± 38.03 pg/ml) and tuberculosis (68.74 ± 39.44 pg/ml) patients (p<0.001). However, no significant difference in cathelicidin levels was observed between tuberculosis and sarcoidosis patients (p=0.966). The optimum cathelicidin cut-off value to distinguish sarcoidosis patients from healthy controls was 107.14 pg/ml (sensitivity 81.5%, specificity 71.2%). CONCLUSION Cathelicidin appears to play different roles in the development of granulomatous lung disease.