Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular and immunophenotypic characterization of AIDS-associated, Epstein-Barr virus-negative, polyclonal lymphoma.

PURPOSE A molecular analysis of non-Hodgkin's lymphomas (NHLs) from patients with AIDS was undertaken to determine the prevalence and immunophenotype of polyclonal B-cell lymphoma. MATERIALS AND METHODS DNA was extracted from 40 diagnostic biopsy specimens obtained from patients seen at University of California, San Francisco (UCSF) between 1986 and 1990. Clonality, infection with Epstein-Barr virus (EBV), and presence of a rearranged c-myc gene were determined by Southern blot analysis. Lymphoma immunophenotypes were determined by frozen-section immunohistochemical analysis. RESULTS The most prevalent genotype of lymphoma in this study was that of polyclonal, EBV-negative tumors with no evidence of c-myc rearrangement (14 of 40; 35%). Monoclonal, EBV-positive tumors with no evidence of c-myc rearrangement comprised the second most prevalent class (10 of 40; 25%), and polyclonal, EBV-positive tumors similar to those seen in transplant patients were observed in only a small subset (three of 40; 8%) of specimens analyzed. The immunophenotype of B cells in the polyclonal EBV-negative subset was equally divided into B-cell-predominant and mixed-phenotype lymphomas, with the latter category containing numerous infiltrating T cells. The B cells in each category were immunoglobulin M-positive (IgM+), CD20+, CD21-. All but one of the polyclonal NHLs had large-cell histology. CONCLUSIONS EBV-negative, AIDS-associated, polyclonal B-cell lymphoma appears to be a new class of human immunodeficiency virus (HIV)-associated disease more prevalent in the current study than any other molecular subclass. The absence of CD21, the EBV receptor, may explain in part the absence of EBV within this polyclonal B-cell population.
Predictors of tuberculosis in first 6 months after initiation of antiretroviral therapy: a case-control study.

SETTING In Africa, 10% of human immunodeficiency virus (HIV) infected adults starting antiretroviral therapy (ART) die within the first year, and tuberculosis (TB) is the leading cause of death. OBJECTIVE To investigate the predictors of ART-associated TB at an adult HIV clinic in Tanzania. DESIGN In this nested case-control study, adults starting ART were screened for TB according to the World Health Organization protocol. Those not diagnosed with TB were observed for 6 months. Patients diagnosed with TB were defined as cases, and controls were selected from among the patients who did not develop TB using incidence density matching. RESULTS Among the 2514 HIV-positive adults in our cohort, 72 (3%) were diagnosed with TB during the first 6 months of ART. By multivariate analysis, baseline characteristics predictive of TB were cough, fever and night sweats; 76% (55/72) of the cases had at least one of these symptoms at the time of starting ART. CONCLUSION Overall, 75% of the patients who developed TB during the first 6 months of ART had TB symptoms at the time of starting ART. Improved TB diagnostics and/or better strategies for empirical anti-tuberculosis treatment are needed for patients with symptoms of TB at ART initiation.
Genetic analysis and evaluation of resistance to thyrotropin and growth hormone-releasing hormone in pseudohypoparathyroidism type Ib.

CONTEXT Pseudohypoparathyroidism (PHP) types Ia and Ib, are caused by mutations in GNAS exons 1-13 and GNAS methylation defects, respectively. PHP-Ia patients show Albright hereditary osteodystrophy (AHO) and resistance toward PTH and additional hormones, whereas PHP-Ib patients do not have AHO and hormone resistance is limited to PTH and, as reported in one paper, TSH. No study addressed the question of GH deficiency in PHP-Ib patients. OBJECTIVES The objective of the study was to screen patients with clinically diagnosed PHP-Ib for genetic defects and investigate the presence of resistance to TSH and GHRH. PATIENTS/METHODS We investigated GNAS differential methylation and STX16 microdeletions in genomic DNA from 10 patients with clinical diagnosis of sporadic PHP-Ib, i.e. PTH resistance without AHO. Resistance to GHRH was assessed by GH response to GHRH plus arginine. Thyroid function and ultrasonography were also evaluated. RESULTS Molecular analysis showed GNAS cluster imprinting defects in all PHP-Ib patients and the first de novo STX16 deletion in one apparently sporadic patient. Subclinical or clinical hypothyroidism due to resistance to TSH was present in nine of 10 patients, whereas a preserved GH response to a GHRH plus arginine test was present in all patients, with one exception. CONCLUSIONS We report the first molecular analysis of Italian patients with PHP-Ib. Clinical investigation shows that, like PHP-Ia patients, PHP-Ib patients are resistant to TSH, whereas they maintain a normal responsiveness to GHRH, at variance with PHP-Ia patients. These data provide new information on this rare disease and emphasize the clinical heterogeneity of genetic defects within GNAS.
How common are motor problems in children with a developmental disorder: rule or exception?

BACKGROUND Few co-morbidity studies have been conducted since the Leeds Consensus Statement on developmental co-ordination disorder (DCD) in 2006. In this Statement, international cut-offs and inclusion criteria were agreed and consequently, the status of DCD changed. Furthermore, most existing co-morbidity studies are small clinical studies, rather than epidemiological studies, resulting in a broad range of co-morbidity rates. DCD has a higher incidence for boys in comparison with girls; questions arise if this preponderance remains the same in combination with other developmental disorders. Therefore, in this study we aimed to determine co-morbidity and gender differences of motor problems in children with a pervasive developmental disorder, a hyperkinetic disorder and/or a speech, language or learning disability. METHODS Profiles of 3608 children (mean age: 9 years 1 month) referred to rehabilitation centres for behavioural, developmental and sensorineural disorders were studied. RESULTS Motor problems were reported in one-fifth of the total sample. Co-morbidity of motor problems in specific disorders varied from almost one-fourth to more than one-third. The male/female ratio was significantly higher in children with motor problems and two or more other disorders, compared with children with motor problems and less than two other disorders. CONCLUSIONS This study indicates that co-morbidity of motor problems with other clinical disorders is not exceptional and developmental deviance is seldom specific to one domain. However, current co-morbidity studies tend to overestimate the number of children with motor problems. In addition, there may be different patterns of symptoms between the genders. These findings stress the importance of assessing motor skills in children with various developmental disorders.
Effect of artificial aging on the roughness and microhardness of sealed composites.

STATEMENT OF THE PROBLEM The application of surface sealant could improve the surface quality and success of composite restorations; however, it is important to assess the behavior of this material when subjected to aging procedures. PURPOSE To evaluate the effect of artificial aging on the surface roughness and microhardness of sealed microhybrids and nanofilled composites. MATERIALS AND METHODS One hundred disc-shaped specimens were made for each composite. After 24 hours, all samples were polished and surface sealant was applied to 50 specimens of each composite. Surface roughness (Ra) was determined with a profilometer and Knoop microhardness was assessed with a 50-g load for 15 seconds. Ten specimens of each group were aged during 252 hours in a UV-accelerated aging chamber or immersed for 28 days in cola soft drink, orange juice, red wine staining solutions, or distilled water. Data were analyzed by two-way analysis of variance and Fischer's test (α=0.05). RESULTS Artificial aging decreased microhardness values for all materials, with the exceptions of Vit-l-escence (Ultradent Products Inc., South Jordan UT, USA) and Supreme XT (3M ESPE, St. Paul, MN, USA) sealed composites; surface roughness values were not altered. Water storage had less effect on microhardness, compared with the other aging processes. The sealed materials presented lower roughness and microhardness values, when compared with unsealed composites. CONCLUSIONS Aging methods decreased the microhardness values of a number of composites, with the exception of some sealed composites, but did not alter the surface roughness of the materials. CLINICAL SIGNIFICANCE The long-term maintenance of the surface quality of materials is fundamental to improving the longevity of esthetic restorations. In this manner, the use of surface sealants could be an important step in the restorative procedure using resin-based materials.
6-Mercaptopurine metabolism in Crohn's disease: correlation with efficacy and toxicity.

BACKGROUND: 6-Mercaptopurine (6-MP) has confirmed short and longterm efficacy in the treatment of IBD. However, the relation between its metabolism, efficacy, and side effects is not well understood. AIMS: To assay 6-MP metabolites and to correlate levels with drug compliance, disease activity, and adverse effects of treatment. PATIENTS: Heparinised blood was obtained prior to daily administration of 6-MP in 25 adolescent Crohn's disease patients (14 ileocolitis, 11 colitis) receiving 1.2 (range 0.4-1.6) mg/kg/day for a mean of 17 (range 4-65) months. METHODS: Erythrocyte free bases 6-thioguanine (6-TG) and 6-methyl-mercaptopurine (6-MMP) were measured (pmol/8 x 10(8) red blood cells) using reverse phase high performance liquid chromatography. RESULTS: Disease activity (modified Harvey-Bradshaw index) improved significantly with 6-MP (p = 0.001). Clinical remission was achieved in 72% of patients, who stopped taking prednisone, or were successfully weaned to a low alternate day dose (< 0.4 mg/kg/OD). Remission correlated well with erythrocyte 6-TG (p < 0.05), but not 6-MMP levels. Neutropenia was associated with 6-MP use (p < 0.005), but did not correlate with erythrocyte 6-MP metabolite levels. One patient refractory to 6-MP had 6-TG, but no measureable 6-MMP production, suggesting deficient thiopurine methyl-transferase activity or poor compliance. 6-MP induced complications (hepatitis, pancreatitis, and marrow suppression) were generally associated with increased 6-MMP levels. CONCLUSIONS: These results suggest that high performance liquid chromatography measurement of erythrocyte 6-MP metabolites may provide a quantitative assessment of patient responsiveness and compliance to treatment. The data support an immunosuppressive role for 6-TG, and potential cytotoxicity of raised 6-MMP levels.
Relative risk of new‐onset diabetes during the first year after renal transplantation in patients receiving tacrolimus or cyclosporine immunosuppression

Abstract: Clinical trials have consistently shown a higher incidence of new‐onset diabetes mellitus with tacrolimus than cyclosporine. However, in protocol‐driven studies steroid doses are comparable in both treatment arms, while in clinical practice steroid dose used in conjunction with tacrolimus or cyclosporine may differ. This retrospective study analysed renal transplant recipients without pre‐existing diabetes receiving tacrolimus (n = 100) or cyclosporine (n = 100) for whom one‐year follow‐up data were available. Diabetes was defined as use of insulin or oral hypoglycemic agents; fasting glucose >6.9 mmol/L; or non‐fasting glucose >11 mmol/L on three consecutive occasions. Tacrolimus‐treated patients were significantly older than cyclosporine‐treated patients (49 ± 14 vs. 44 ± 13 yr, p < 0.05) and received a significantly lower cumulative dose of corticosteroids over the first three months post‐transplant (1284 ± 379 vs. 1714 ± 486 mg, p < 0.0001). At 3, 6, 9 and 12 months significantly more tacrolimus‐treated patients had new‐onset diabetes than cyclosporine‐ treated patients. At 12 months, 18 patients receiving tacrolimus and two receiving cyclosporine had diabetes (p < 0.0001). There was a clear relationship between age and incidence of new‐onset diabetes at three months in the tacrolimus cohort. After stratifying patients by age group, the frequency of diabetes was significantly higher with tacrolimus than with cyclosporine in patients aged 40–60 yr [8/46 (17.4%) vs. 2/48 (4.2%), p < 0.05] and >60 yr [9/28 (32.1%) vs. 0/14 (0%), p < 0.05]. The mean tacrolimus trough level during the first three months was similar in patients with diabetes (13.1 ± 2.3 ng/mL) or without diabetes (13.0 ± 2.8 ng/mL, n.s.). These results indicate that new‐onset diabetes is strongly and significantly associated with tacrolimus vs. cyclosporine in renal transplant recipients, even when steroid dosing is lower with tacrolimus.
Management of Coronary Artery Disease in End‐Stage Renal Disease

Despite a substantial number of patients with end‐stage renal disease who have coronary artery disease, the comparative effectiveness of revascularization procedures such as coronary artery bypass grafting and percutaneous coronary intervention remain unclear. Innovations in the field of coronary artery revascularization and concomitant changes in the standard of practice have improved outcomes in general. However, meaningful clinical decision‐making remains difficult because it requires clinicians to extrapolate evidence derived from studies in the general population to patients with kidney disease for whom there is limited information from intervention trials. In non‐randomized studies, this high‐risk population for cardiovascular morbidity and mortality appear to derive substantial benefits from coronary revascularization. However, specific treatment decisions are often made based upon individual circumstances and contexts that are not well captured in these studies. This article reviews the available evidence, and its limitations, for deciding between various revascularization strategies for patients with end‐stage renal disease. Several considerations that arise while making such decisions are discussed.
Concentric or eccentric training effect on eccentric exercise-induced muscle damage.

PURPOSE The purpose of this study was to compare changes in muscle damage indicators following 24 maximal eccentric actions of the elbow flexors (Max-ECC) between the arms that had been previously trained either eccentrically or concentrically for 8 wk. METHODS Fifteen subjects performed three sets of 10 repetitions of eccentric training (ECC-T) with one arm and concentric training (CON-T) with the other arm once a week for 8 wk using a dumbbell representing 50% of maximal isometric force of the elbow flexors (MIF) determined at the elbow joint of 90 degrees (1.57 rad). The dumbbell was lowered from a flexed (50 degrees, 0.87 rad) to an extended elbow position (180 degrees, 3.14 rad) in 3 s for ECC-T, and lifted from the extended to the flexed position in 3 s for CON-T. Max-ECC was performed 4 wk after CON-T and 6 wk after ECC-T. Changes in MIF, range of motion (ROM), upper arm circumference (CIR), muscle soreness (SOR), and plasma creatine kinase (CK) activity were compared between the ECC-T and CON-T arms. RESULTS The first ECC-T session produced larger decreases in MIF and ROM, and larger increases in CIR and SOR compared with CON-T. CK increased significantly (P < 0.01) and peaked 4 d after the first training session, but did not increase in the following sessions. All measures changed significantly (P < 0.01) following Max-ECC; however, the changes were not significantly different between ECC-T and CON-T arms. CONCLUSION These results showed that ECC-T did not mitigate the magnitude of muscle damage more than CON-T, and CON-T did not exacerbate muscle damage.
Solutions to problems with deep learning

Despite the several successes of deep learning systems, there are concerns about their limitations, discussed most recently by Gary Marcus. This paper discusses Marcus's concerns and some others, together with solutions to several of these problems provided by the "P theory of intelligence" and its realisation in the "SP computer model". The main advantages of the SP system are: relatively small requirements for data and the ability to learn from a single experience; the ability to model both hierarchical and non-hierarchical structures; strengths in several kinds of reasoning, including `commonsense' reasoning; transparency in the representation of knowledge, and the provision of an audit trail for all processing; the likelihood that the SP system could not be fooled into bizarre or eccentric recognition of stimuli, as deep learning systems can be; the SP system provides a robust solution to the problem of `catastrophic forgetting' in deep learning systems; the SP system provides a theoretically-coherent solution to the problems of correcting over- and under-generalisations in learning, and learning correct structures despite errors in data; unlike most research on deep learning, the SP programme of research draws extensively on research on human learning, perception, and cognition; and the SP programme of research has an overarching theory, supported by evidence, something that is largely missing from research on deep learning. In general, the SP system provides a much firmer foundation than deep learning for the development of artificial general intelligence.
Orthostatic hypotension, diabetes, and falling in older patients: a cross-sectional study.

BACKGROUND Although orthostatic hypotension (OH) is more prevalent in old age, and in patients with diabetes, the prevalence of OH in older patients with type 2 diabetes mellitus is unknown. AIM To establish the prevalence of OH, and its association with falling, in home-dwelling older participants with and without type 2 diabetes. DESIGN AND SETTING A cross-sectional study in primary care in the Netherlands. METHOD A total of 352 patients with type 2 diabetes, and 211 without participated in this study. OH was defined as a fall in blood pressure of at least 20 mmHg systolic or 10 mmHg diastolic after either 1 or 3 minutes in an upright position. Feelings of dizziness, light-headedness, or faintness during the standing period were documented as orthostatic complaints. Fall risk was assessed with a validated risk profile instrument. RESULTS The prevalence of OH was 28% (95% CI = 24% to 33%) and 18% (95% CI = 13% to 23%) in participants with and without type 2 diabetes, respectively. OH was not related to falling, while the presence of orthostatic complaints in itself was associated with both previous fall incidents as well as a high fall risk, even after adjustment for OH. The adjusted odds ratios were 1.65 (95% CI = 1.00 to 2.72) and 8.21 (95% CI = 4.17 to 16.19), respectively. CONCLUSION OH is highly prevalent in home-dwelling older people with and without type 2 diabetes. Those with orthostatic complaints had an increased risk for falling, whereas those with OH were not.
Taxonomic and molecular identification of mesocriconema and criconemoides species (nematoda: criconematidae).

Populations of Mesocriconema curvatum, M. kirjanovae, M. onoense, M. ornatum, M. sphaerocephala, M. surinamense, M. vadense, M. xenoplax, and Criconemoides informis from different geographical areas in the continental United States were characterized morphologically and molecularly. A new ring nematode from Washington County, Arkansas, is also described and named Mesocriconema ozarkiense n. sp. , This new species is characterized by females with small flattened submedian lobes, lower than or at the same level as the labial disc, vagina straight, very well developed spermatheca without sperm, no more than one anastomoses, L=379-512 μm, V=89-93, stylet length = 49-61 μm, R=107-119, annuli with slightly crenate margins on tail portion and a simple anterior vulval lip. The molecular characterization of M. ozarkiense n. sp. using the ITS rRNA gene sequence and the phylogenesis relationship of this new species with the ring nematodes included in this study are provided.
Spontaneous mutations in the human CMV HLA class I homologue UL18 affect its binding to the inhibitory receptor LIR‐1/ILT2/CD85j

Human cytomegalovirus (HCMV) down‐regulates cell surface expression of HLA class I molecules (HLA‐I). UL18, an HCMV‐encoded HLA‐I homologue, has been proposed to protect virus‐infected cells against NK cell recognition by engaging the inhibitory receptor leukocyte Ig‐like receptor (LIR)‐1, which also binds a broad spectrum of HLA‐I alleles, including HLA‐G1. Because genetic and biological differences exist among HCMV strains, we characterized laboratory (AD169) and clinical (4636, 13B, 109B) strain‐derived UL18 proteins. Compared to the known AD169‐derived UL18, mutations were found in clinical strain‐derived UL18. They were clustered in the α3 domain (13B), previously shown to be critical for LIR‐1 binding, or in the α1 domain (4636). In cytotoxicity assays, pretreatment of LIR‐1+ NKL with soluble 4636‐UL18 completely abolished LIR‐1‐dependent protection from NK lysis, conferred by the expression of HLA‐G1 on target cells (721.221‐HLA‐G1+). Similarly, flow cytometry, Biacore and ELISA experiments showed 4636‐UL18 and 13B‐UL18 to have the strongest binding capacity to LIR‐1. Our results suggest the importance of two independent UL18 regions for LIR‐1 binding, one localized on the tip of the α3 domain, and another composed of two loops that emerge from the α1 domain. Strain variations in these domains may result in different UL18‐mediated effects on LIR‐1+ cells during the course of HCMV infection.
Altered expression of the retinoblastoma gene product in human sarcomas.

BACKGROUND The retinoblastoma-susceptibility (Rb) gene is a prototype tumor-suppressor gene originally isolated from patients with heritable retinoblastoma. This gene encodes a nuclear phosphoprotein whose expression is altered in several types of human tumors. METHODS We studied the expression of the Rb protein in 44 primary and 12 metastatic high-grade human sarcomas by means of immunohistochemical methods and Western blotting. Computerized image analysis was used to quantify the level of Rb gene product in individual tumor cells. The expression of the Rb gene was then correlated with clinical outcome in the patients with primary tumors. RESULTS Of the 44 patients with primary sarcomas, 13 (30 percent) had tumors with normal, homogeneous expression of the Rb protein in essentially all tumor cells. Thirty-one patients with primary tumors (70 percent) had altered Rb expression; in 18 (40 percent) the Rb protein was heterogeneously expressed, and in 13 (30 percent) it was detected in fewer than 20 percent of the tumor cells. All 12 of the patients with metastatic sarcomas had altered expression of the Rb protein. When the findings in the patients with primary tumors were correlated with clinical outcome, survival was found to be significantly increased in the patients whose tumors had homogeneous Rb expression, as compared with those with either heterogeneous expression (P = 0.026) or no expression (P = 0.012). CONCLUSIONS Tumors in which the expression of Rb gene product was decreased were more aggressive than tumors in which this protein was expressed by nearly all cells. The Rb gene product may be an important prognostic variable in patients with these tumors.