Miracle-dz/UniFAR-FTUs huggingface dataset:
A retrospective analysis of prognostic factors predictive of lymph-node metastasis and recurrence in thyroid papillary microcarcinoma.

AIM The literature is inconclusive concerning the prognostic factors and therapeutic management of papillary thyroid microcarcinoma (PTMC). Herein we report on our extensive experience with PTMC in relation to clinicopathological characteristics and prognostic factors. METHODS In all, 248 patients that were diagnosed and treated for PTMC between 2007 and 2012 were retrospectively analyzed. Demographic and tumor characteristics at presentation, and recurrence during follow-up were noted. RESULTS Total thyroidectomy and radioactive iodine (RAI) ablation treatment were performed in all patients. Bilateral involvement, vascular and capsular invasion, extra-thyroidal extension, and lymph node metastasis occurred significantly more frequently in patients with tumor size>5 mm (P<0.05). Multivariate statistical analysis showed that a clinically suspected diagnosis (OR:0.095; P=0.043) and elevated thyroglobulin (TG) level (OR: 1.083; P=0.011; cut-off value≥7.98 ngmL(-1)) were significant and independent risk factors for lymph node metastasis, with a sensitivity of 57% and specificity of 83%. After a median follow-up of 2 years (range:0.3-11 years), 10 (4%) of the 248 patients had recurrent disease. According to multivariate analysis, lymph node metastasis (OR: 51.4; P=0.003) was the only independent predictor of recurrence. CONCLUSION Our findings revealed that serum TG level and a clinically suspected diagnosis were risk factors for lymph node metastasis, while nodal metastasis was a predictor of recurrence.
Influence of tibial component posterior slope on in vivo knee kinematics in fixed‐bearing total knee arthroplasty

The relation between prosthesis component kinematics and posterior slope of the tibial component in total knee arthroplasty is much debated. Three‐dimensional kinematics of the replaced knee was obtained by video fluoroscopy in 23 knees treated by cruciate‐retaining or cruciate‐substituting arthroplasty. Relative position and orientation of the metal components were calculated in stair ascending, getting up from and sitting down on a chair, and single step up‐and‐down. Significant correlations were found between tibial component posterior slope and anteroposterior position of tibiofemoral lateral contact and between this slope and maximum knee flexion. These correlations were task and design specific. However, the average of the tibiofemoral contact positions over all three motor tasks was slightly posterior to the midline of the tibial base plate, reaching at most 84% of its anteroposterior dimension. Performing a posterior slope of the tibial cut does not put total knee arthroplasty with high conforming designs at higher risk of failure, even when large posterior inclinations need to be achieved. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
AMEE Guide No. 25: The assessment of learning outcomes for the competent and reflective physician

Two important features of contemporary medical education are recognized. The first is an emphasis on assessment as a tool to ensure quality in training programmes, to motivate students and to direct what they learn. The second is a move to outcome-based education where the learning outcomes are defined and decisions about the curriculum are based on these. These two trends are closely related. If teachers are to do a better job of assessing their students, they need an understanding of the assessment process, an appreciation of the learning outcomes to be assessed and a recognition of the most appropriate tools to assess each outcome. Assessment tools selected should be valid, reliable, practical and have an appropriate impact on student learning. The preferred assessment tool will vary with the outcome to be assessed. It is likely to be some form of written test, a performance test such as an OSCE in which the student’s competence can be tested in a simulated situation, and a test of the student’s behaviour over time in clinical practice, based on tutors’ reports and students’ portfolios. An assessment profile can be produced for each student which highlights the learning outcomes the student has achieved at the required standard and other outcomes where this is not the case. For educational as well as economic reasons, there should be collaboration across the continuum of education in test development as it relates to the assessment of learning outcomes and in the implementation of a competence-based approach to assessment.
The Relation between Body Mass Index, Mental Health, and Functional Disability: A European Population Perspective

Objective: To examine the association between body mass, mental disorders, and functional disability in the general population of 6 European countries. Method: Data (n = 21 425) were derived from the European Study on the Epidemiology of Mental Disorders (ESEMeD). The third version of the Composite International Diagnostic Interview was administered to assess mental disorders (mood, anxiety, and alcohol disorders) according to the Diagnostic Statistical Manual of Mental Disorders-fourth edition, body mass index (BMI) (kg/m2, based on self-reported height and weight), and functional disability in the previous 30 days, assessed with the World Health Organization Disablement Assessment Scale—second version. Results: About 3% of the respondents were underweight (BMI < 18.5 kg/m2), 53% had normal weight (BMI 18.5 to 24.9 kg/m2), 33% were overweight (BMI 25 to 29.9 kg/m2), and the remaining 12% met criteria for obesity (BMI > 30.0 kg/m2). Compared with individuals of normal weight, obese individuals were more likely to have mood (OR 1.3; 95%CI, 1.0 to 1.8) or more than one mental disorder (OR 1.4; 95%CI, 1.0 to 2.2). BMI had no impact on work loss days, whereas mental disorders had a considerable effect on work loss days. Conclusions: This is the first cross-national study investigating the role between BMI, mental disorders, and functional disability in the general population. Being overweight or obese is a common condition in the 6 ESEMeD countries. Although there is a moderate association between obesity and mental disorders, BMI did not independently influence functional disability.
Microbial inorganic pyrophosphatases.

INTRODUCTION. 169 INTRACELLULAR LOCALIZATION. 169 REGULATION OF PPase SYNTHESIS. 170 Effects of Culture Conditions . 170 PPase Mutants. 170 Inhibition of Cell Division and Macromolecular Synthesis . 171 POLYMORPHIC FORMS OF PPase . 171 REGULATION AT THE ACTIVITY LEVEL . 171 Problems Encountered in Kinetic Studies. 171 Kinetic Survey. 172 Allosteric PPases. 173 Regulation of PPase Activity by Adenylate Nucleotides . 174 Regulation of PPase Activity by Glutathione . 175 SUMMARY. 175 ACKNOWLEDGMENTS : . 176 LITERATURE CITED . 176
Fast and accurate computation of the 13C chemical shifts for an alanine‐rich peptide

The purpose of this work is, first, to present a fast and accurate technique to compute Boltzmann‐averaged values of the quantum‐chemical 13C chemical shifts for each amino acid in oligopeptides, demonstrated here by an application to the peptide Ac‐XXAAAAAAAOO‐NH2 (where X denotes diaminobutyric acid, A is alanine, and O is ornithine) [XAO] and, second, to discuss the capability of the 13Cα and 13Cβ chemical shifts to distinguish the PPII conformation from the α‐helix and statistical‐coil conformations. Use is made of a combination of approaches, summarized as follows: (1) derivation of an ensemble of conformations by using a molecular mechanics technique; (2) use of a clustering procedure to form families and build a reduced set of conformations consisting of the lowest‐energy conformations of each family, and (3) computation of the 13C chemical shifts for the lowest‐energy conformations of each family, using a quantum‐chemical approach that treats a selected residue, or group of residues, with a 6‐311+G(2d,p) locally‐dense basis set, while the remaining residues in the sequence are treated with a 3‐21G basis set. The whole procedure is quite accurate and speeds up the computation of the Boltzmann‐averaged values of the 13C‐chemical shifts by several orders of magnitude. The present application sheds some light on the conformational preference for alanine and non‐alanine residues to occupy the PPII helical region of the Ramachandran map. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Apolipoprotein E Phenotype Alone Does Not Influence Survival in Alzheimer’s Disease: A Population-Based Longitudinal Study

Apolipoprotein E4 (ApoE4) phenotype is a known risk factor for development of Alzheimer’s disease (AD). Contradictory results exist concerning the role of ApoE4 in the rate of decline and mortality in AD. Conflicting findings have also been reported about ApoE and gender interactions with respect to survival. We examined the survival of subjects with AD and non-AD controls with respect to ApoE phenotype and gender in a population-based longitudinal study. Cognitive evaluation was performed for a total of 980 subjects (then aged 69–78 years), and 48 cases with AD were identified. ApoE4 phenotype was more frequently present among subjects with AD. In the whole study population, survival was not related to the presence of AD or ApoE4 phenotype. Risk of death was increased for men compared to women, independently of the ApoE4 phenotype (HR 0.5, 95% confidence interval 0.44–0.69). In subjects with AD, the presence of ApoE4 alone did not influence survival. However, in the AD group, ApoE4-negative men had significantly increased risk of mortality compared to the risk in ApoE4-negative women (p < 0.01). We conclude that the presence of ApoE4 phenotype or AD did not influence mortality in the aged population. Once AD had become manifest, ApoE4 alone did not relate to survival. However, in subjects with AD not carrying ApoE4, men had reduced survival compared to women.
Patient and Technique Survival on Capd in Turkey

Objective To analyze the status of continuous ambulatory peritoneal dialysis (CAPD) in 12 centers in Turkey. Design Retrospective study of CAPD technique and patient outcome. Setting University hospital renal units. Patients 334 patients [205 males (61%), 129 (39%) females; mean age 42.2 ± 13.8 years; mean follow-up time 23.5 ± 18.3 months] beginning CAPD between March 1992 and December 1999, and having a minimum follow-up of 3 months. Outcome Measure Patient survival, technique survival, and duration of hospitalization. Results Mean weekly Kt/V urea was 1.9 ± 0.8, weekly creatinine clearance was 62.9 ± 8.5 L/1.73 m2, and mean serum albumin level was 3.7 ± 0.6 g/dL. 93 patients (28%) were withdrawn from peritoneal dialysis due to death (12.6%), transplantation (3.9%), transfer to hemodialysis (8.7%), patient failure to adapt (1.5%), and other reasons (1.2%). The major causes of death were cardiovascular disease (60%), infection (19%), malignancy (2%), and others (19%). Cox proportional hazard model analysis indicated age, serum albumin levels, comorbidity, and functional status affected survival and hospitalization (p < 0.05), whereas gender and Kt/V did not (p > 0.05). Estimation of patient survival by Kaplan–Meier analysis showed 94.2%, 88.6%, 84.5%, and 68.9% at 1, 2, 3, and 5 years respectively. Technique survival estimate by Kaplan–Meier analysis was 96.6%, 91.1%, 90.4%, and 77.4% at 1, 2, 3, and 5 years respectively. Conclusion Peritoneal dialysis is an acceptable method of renal replacement therapy in Turkey. There is controversy regarding the usefulness of Kt/V in predicting mortality and morbidity.
Production and characterization of monoclonal antibodies to cell wall antigens of Aspergillus fumigatus

Two murine monoclonal antibodies (MAbs) against Aspergillus fumigatus were produced and characterized. Splenocytes from cell wall-immunized BALB/c mice were fused with SP2/0 myeloma cells. The hybridomas were screened with a cold alkali (CA) extract of mycelium containing protein, mannose, and galactose, and two MAbs of the immunoglobulin M class were purified from ascites fluid. MAbs 1 and 40 were characterized by double immunodiffusion against CA antigen, indirect enzyme immunoassay with mannans of Candida albicans serotypes A or B or Candida tropicalis, indirect immunofluorescence with C. albicans- or A. fumigatus-infected tissues, indirect immunofluorescence with smears of other pathogenic fungi, Western blotting (immunoblotting) with the lectin concanavalin A or BS-1 from the seeds of Bandeirea simplicifolia, and immunoelectron microscopy. MAb 1 did not cross-react with Candida mannan and recognized a periodate-sensitive, pronase- and heat-resistant epitope in CA antigen and three mannose- and galactose-containing components (80, 62, and 49 kilodaltons) of a mycelial homogenate. Immunoelectron microscopy demonstrated binding of MAb 1 to the inner cell wall and intracellular membranes of hyphae and conidia of A. fumigatus. Circulating antigen was detected in experimental invasive aspergillosis by inhibition enzyme immunoassay with MAb 1 and CA antigen. MAb 40 was a nonprecipitating antibody cross-reactive with Candida species, and competition for an epitope located diffusely in the cell wall of A. fumigatus hyphae was demonstrated by incubating MAb 40 with mannan of C. albicans serotype A. These results suggest that MAb 1 recognizes immunodominant oligogalactoside side chains of A. fumigatus galactomannan, while MAb 40 binds to mannopyranosyl side chains common to A. fumigatus galactomannan and C. albicans mannan.
A prognostic model for survival after salvage treatment with FLAG‐Ida +/− gemtuzumab‐ozogamicine in adult patients with refractory/relapsed acute myeloid leukaemia

The combination of fludarabine, cytarabine, idarubicin, and granulocyte colony‐stimulating factor (FLAG‐Ida) is widely used in relapsed/refractory acute myeloid leukaemia (AML). We retrospectively analysed the results of 259 adult AML patients treated as first salvage with FLAG‐Ida or FLAG‐Ida plus Gentuzumab‐Ozogamicin (FLAGO‐Ida) of the Programa Español de Tratamientos en Hematología (PETHEMA) database, developing a prognostic score system of survival in this setting (SALFLAGE score). Overall, 221 patients received FLAG‐Ida and 38 FLAGO‐Ida; 92 were older than 60 years. The complete remission (CR)/CR with incomplete blood count recovery (CRi) rate was 51%, with 9% of induction deaths. Three covariates were associated with lower CR/CRi: high‐risk cytogenetics and t(8;21) at diagnosis, no previous allogeneic stem cell transplantation (allo‐SCT) and relapse‐free interval <1 year. Allo‐SCT was performed in second CR in 60 patients (23%). The median overall survival (OS) of the entire cohort was 0·7 years, with 22% OS at 5‐years. Four independent variables were used to construct the score: cytogenetics, FLT3‐internal tandem duplication, length of relapse‐free interval and previous allo‐SCT. Using this stratification system, three groups were defined: favourable (26% of patients), intermediate (29%) and poor‐risk (45%), with an expected 5‐year OS of 52%, 26% and 7%, respectively. The SALFLAGE score discriminated a subset of patients with an acceptable long‐term outcome using FLAG‐Ida/FLAGO‐Ida regimen. The results of this retrospective analysis should be validated in independent external cohorts.
Three‐Dimensional Anatomy of the Equine Sternum

The sternum is a frequently used anatomical site to obtain bone marrow for diagnostic and therapeutic purposes in equine medicine and surgery. For a safe and reproducible aspiration of sternal bone marrow, a reliable anatomical description of the sternum is mandatory. However, the anatomical literature provides very heterogeneous information concerning the structure and number of sternebrae. Isolated sterna (horses of different ages) underwent clinical computed tomography, and single sternebrae were scanned by microcomputed tomography. Data sets were analysed in detail, the dimensions of each sternebra were determined, and correlations to the age and weight were generated. A uniform arrangement of seven sternebrae within the equine sternum was obtained, whereas the 6th and 7th sternebrae were fused in all sterna. The cranial sternebrae (sternebrae 1–3) had a lentiform shape with flattened lateral sides, while the caudal sternebrae (6 and 7) were flattened dorso‐ventrally. In contrast, sternebrae 4 and 5 were spherical. The single sternebrae were well demarcated to the chondral sternum and showed two different zones. The periphery consisted of radiodense woven tissue, while in the centre the radiodense tissue was loosely arranged and contained large cavities with radiolucent tissue. A thin lamina (substantia corticalis) of <1 mm was arranged around the peripheral zone. There was no correlation between the body weight and the dimensions of the sternebrae, but there was a positive correlation to the age of the horses. The obtained data provide a sufficient basis to establish a standard nomenclature of the equine sternum.
Anti-proliferative effects of physiological concentrations of enterolactone in models of prostate tumourigenesis.

SCOPE There is evidence that a mammalian lignan, enterolactone (ENL), decreases the proliferation rate of prostate cancer cells, although previous studies have used concentrations difficult to achieve through dietary modification. We have therefore investigated the anti-proliferative effects of ENL in an in vitro model of prostate tumourigenesis at concentrations reported to occur in a range of male populations. METHODS AND RESULTS The effects of 0.1 and 1 μM ENL on three markers of viability and proliferation (metabolic activity, growth kinetics, and cell cycle progression) were assessed in the RWPE-1, WPE1-NA22, WPE1-NB14, WPE1-NB11, WPE1-NB26, LNCaP, and PC-3 cell lines over 72 h. Based on these data, we quantified the expression levels of 12 genes involved in the control of DNA replication initiation using TaqMan real-time PCR in the WPE1-NA22, WPE1-NB14, WPE1-NB11, and WPE1-NB26 cell lines. ENL significantly inhibited the abnormal proliferation of the WPE1-NB14 and WPE1-NB11 cell lines and appears to be a consequence of decreased expression of abnormal chromatin licensing and DNA replication factor 1. CONCLUSION In contrast to previous studies, concentrations of ENL that are reported after dietary intervention restrict the proliferation of early-stage tumourigenic prostate cell lines by inhibiting the abnormal formation of complexes that initiate DNA replication.
Nucleolar GTP-binding Protein-1 (NGP-1) Promotes G1 to S Phase Transition by Activating Cyclin-dependent Kinase Inhibitor p21Cip1/Waf1*

Background: Breast cancer autoantigen nucleolar GTP-binding protein-1 (NGP-1) is overexpressed in cancers. Results: NGP-1 promotes G1 to S phase transition by modulating the p53/p21 pathway. Conclusion: CDK inhibitor, p21, enhances cell proliferation in certain situations. Significance: This study provides evidence that p21 induces cell proliferation in addition to its traditional tumor suppressor function. Nucleolar GTP-binding protein (NGP-1) is overexpressed in various cancers and proliferating cells, but the functional significance remains unknown. In this study, we show that NGP-1 promotes G1 to S phase transition of cells by enhancing CDK inhibitor p21Cip-1/Waf1 expression through p53. In addition, our results suggest that activation of the cyclin D1-CDK4 complex by NGP-1 via maintaining the stoichiometry between cyclin D1-CDK4 complex and p21 resulted in hyperphosphorylation of retinoblastoma protein at serine 780 (p-RBSer-780) followed by the up-regulation of E2F1 target genes required to promote G1 to S phase transition. Furthermore, our data suggest that ribosomal protein RPL23A interacts with NGP-1 and abolishes NGP-1-induced p53 activity by enhancing Mdm2-mediated p53 polyubiquitination. Finally, reduction of p-RBSer-780 levels and E2F1 target gene expression upon ectopic expression of RPL23a resulted in arrest at the G1 phase of the cell cycle. Collectively, this investigation provides evidence that NGP-1 promotes cell cycle progression through the activation of the p53/p21Cip-1/Waf1 pathway.
A reassessment of sexual dimorphism in human senescence: Theory, evidence, and causation

Age‐specific mortality rates of men are higher than those of women, and men have shorter average life spans than women. This has been interpreted as evidence of sexual dimorphism in rates of senescence. However, because mortality can be caused by numerous factors in addition to senescence, higher mortality rates do not necessarily indicate more rapid senescence. In this paper, we (1) emphasize the necessity of decoupling mortality and senescence when considering sexual dimorphism in senescence, (2) present a theoretical framework for the hypothesis that selection affects senescence in human males and females differently due to different life history characteristics, (3) consider phenotypic evidence from the literature that human males show a later onset of senescence than human females, despite exhibiting higher mortality rates, and (4) discuss the potential roles of mutation accumulation and antagonistic pleiotropy in the evolution of sexual dimorphism in senescence. Am. J. Hum. Biol. 18:161–168, 2006. © 2006 Wiley‐Liss, Inc.
Macrophages: important players in primary Sjögren’s syndrome?

Primary Sjögren’s syndrome (pSS) is a chronic autoimmune disorder characterized by immune-mediated destruction of the salivary and lacrimal glands with unknown etiology. Due to recent research utilizing human subjects as well as laboratory animal models, our understanding of the pathophysiological and immunological mechanisms of pSS has made great strides. As a consequence, targeted, immune-based therapies are gaining increased attention as the ideal way to conquer autoimmune diseases like pSS. Currently, however, there is no effective treatment to target specific immunological events or effector immune cells in the pathogenesis of pSS (discussed in other reviews of the current issue). Here, we summarize our current understanding and knowledge of the roles of monocytes/macrophages in the pathogenesis of pSS. Human studies, especially utilizing salivary gland biopsies, demonstrate the infiltration of macrophages and its correlation with disease severity. Moreover, animal model studies have shown the functional involvement of macrophages in promoting the ocular component of pSS.