Miracle-dz/UniFAR-FTUs huggingface dataset:
The risk of malignancy index (RMI) in diagnosis of ovarian malignancy.

OBJECTIVE To evaluate the ability of two risk of malignancy indices (RMI) based on serum levels of CA 125, ultrasonographic score, and menopausal status to discriminate between benign and borderline or malignant ovarian tumor. MATERIALS AND METHODS A retrospective study was conducted in 209 women with pelvic masses admitted for laparotomy at Srinagarind Hospital, between January 2002 and December 2007. The sensitivity, specificity and positive predictive (PPV) and negative predictive (NPV) values of two RMI were calculated. RESULTS Using a cut-off level of 200 to indicate malignancy, the RMI 1 gave sensitivity of 70.6%, specificity of 83.9%, PPV of 75%, and NPV of 80.6%. The RMI 2 gave sensitivity of 80%, specificity of 78.2%, PPV of 71.6%, and NPV of 85.1%. The RMI 2 was significantly better in predicting malignancy than RMI 1. CONCLUSION The RMI is able to discriminate between benign and borderline or malignant ovarian tumor.
Challenges of flow‐cytometric estimation of nuclear genome size in orchids, a plant group with both whole‐genome and progressively partial endoreplication

Nuclear genome size is an inherited quantitative trait of eukaryotic organisms with both practical and biological consequences. A detailed analysis of major families is a promising approach to fully understand the biological meaning of the extensive variation in genome size in plants. Although Orchidaceae accounts for ∼10% of the angiosperm diversity, the knowledge of patterns and dynamics of their genome size is limited, in part due to difficulties in flow cytometric analyses. Cells in various somatic tissues of orchids undergo extensive endoreplication, either whole‐genome or partial, and the G1‐phase nuclei with 2C DNA amounts may be lacking, resulting in overestimated genome size values. Interpretation of DNA content histograms is particularly challenging in species with progressively partial endoreplication, in which the ratios between the positions of two neighboring DNA peaks are lower than two. In order to assess distributions of nuclear DNA amounts and identify tissue suitable for reliable estimation of nuclear DNA content, we analyzed six different tissue types in 48 orchid species belonging to all recognized subfamilies. Although traditionally used leaves may provide incorrect C‐values, particularly in species with progressively partial endoreplication, young ovaries and pollinaria consistently yield 2C and 1C peaks of their G1‐phase nuclei, respectively, and are, therefore, the most suitable parts for genome size studies in orchids. We also provide new DNA C‐values for 22 orchid genera and 42 species. Adhering to the proposed methodology would allow for reliable genome size estimates in this largest plant family. Although our research was limited to orchids, the need to find a suitable tissue with dominant 2C peak of G1‐phase nuclei applies to all endopolyploid species. © 2015 International Society for Advancement of Cytometry
Exercise tolerance and daily life in McArdle's disease

McArdle's disease is a common disorder of muscle metabolism and is due to myophosphorylase deficiency. The major complaint of patients with this disease is effort intolerance. Although the clinical features of affected patients are well known, their daily lifestyle is not well documented. The main objective of this work was to assess their mean daily energy expenditure (DEE) and compare it with control subjects. Thirty patients and 87 control subjects completed a questionnaire. A 3‐day self‐record of daily physical activities was used to estimate the mean DEE for patients and control subjects. A separate section of the questionnaire was used to assess patients' clinical features and daily lifestyle. The DEE of patients (44.1 ± 6.9 kcal/kg) was not significantly different from control subjects (44.5 ± 5.6 kcal/kg). Half of the patients with McArdle's disease performed a daily physical leisure activity as sport, sometimes at a high level (17%). Despite large individual variation, physical abilities and patients' symptoms were negatively correlated. Physical leisure activity significantly decreased the sensation of muscle pain (P < 0.03). These findings show that patients with McArdle's disease do not have a strictly sedentary lifestyle. Moreover, physical exercise appears to have positive effects on the main clinical features, such as effort intolerance. Thus, regular, moderate physical activity may be beneficial in McArdle's disease. Muscle Nerve, 2005
Combining ondansetron and naltrexone effectively treats biologically predisposed alcoholics: from hypotheses to preliminary clinical evidence.

BACKGROUND Individuals considered to be early onset alcoholics (EOA) are characterized by an early onset age, a broad range of antisocial behaviors, high familial loading, and presumed biological disease predisposition. Ondansetron, a 5-HT3 antagonist, improves drinking outcomes and increases abstinence rates among EOA. Individuals with high familial loading for developing alcoholism have lower levels of beta-endorphin and demonstrate a more pronounced increase in beta-endorphin levels in response to alcohol administration compared with individuals who do not have alcoholic relatives. The propensity for naltrexone (a mu opioid antagonist) to reduce alcohol's rewarding effects and drinking in humans is greatest in individuals with high familial loading. Predicated on the added knowledge that 5-HT3 receptors may themselves mediate alcohol reward via activation of the endogenous opioid system, we hypothesized that the combination of ondansetron and naltrexone would act synergistically and would be an effective treatment in EOA. METHODS We conducted an 8-week double-blind placebo controlled clinical trial in which 20 EOA were randomized to receive ondansetron (4 microg/kg twice a day) + naltrexone (25 mg twice a day) or placebo as an adjunct to weekly standardized group Cognitive Behavioral Therapy. RESULTS At endpoint, subjects who received ondansetron + naltrexone (n = 10), compared with those who received placebo (n = 10), had fewer drinks/day (covariate adjusted mean 0.99 +/- 0.60 vs. 3.68 +/- 0.63; F1, 16 = 9.35,p = 0.008; effect size = 1.42), drinks/drinking day (covariate adjusted mean 3.14 +/- 0.87 vs. 6.76 +/- 0.71; F1, 13 = 10.45, p = 0.007; effect size = 1.71), and a trend toward increased percent days abstinent (covariate adjusted mean 69.76 +/- 8.64 vs. 48.24 +/- 9.12; F1, 16 = 3.58, p = 0.08; effect size = 0.88). CONCLUSIONS Ondansetron plus naltrexone seems to synergistically improve the drinking outcomes of EOA. Larger scale studies that test these medications, both alone and together, among various alcoholic subtypes are needed to establish and extend these promising findings.
Effect of calpain and proteasome inhibition on Ca2+‐dependent proteolysis and muscle histopathology in the mdx mouse

Dystrophin deficiency is the underlying molecular cause of progressive muscle weakness observed in Duchenne muscular dystrophy (DMD). Loss of functional dystrophin leads to elevated levels of intracellular Ca2+, a key step in the cellular pathology of DMD. The cysteine protease calpain is activated in dystrophin‐deficient muscle, and its inhibition is regarded as a potential therapeutic approach. In addition, previous work has shown that the ubiquitin‐proteasome system also contributes to muscle protein breakdown in dystrophic muscle and, therefore, also qualifies as a potential target for therapeutic intervention in DMD. The relative contribution of calpain‐ and proteasome‐mediated proteolysis induced by increased Ca2+ levels was characterized in cultured muscle cells and revealed initial Ca2+ influx‐dependent calpain activity and subsequent Ca2+‐independent activity of the ubiquitin‐proteasome system. We then set out to optimize novel small‐molecule inhibitors that inhibit both calpain as well as the 20S proteasome in a cellular system with impaired Ca2+ homeostasis. On administration of such inhibitors to mdx mice, quantitative histological parameters improved significantly, in particular with compounds strongly inhibiting the 20S proteasome. To investigate the role of calpain inhibition without interfering with the ubiquitin‐proteasome system, we crossed mdx mice with transgenic mice, overexpressing the endogenous calpain inhibitor calpastatin. Although our data show that proteolysis by calpain is strongly inhibited in the transgenic mdx mouse, this calpain inhibition did not ameliorate muscle histology. Our results indicate that inhibition of the proteasome rather than calpain is required for histological improvement of dystrophin‐deficient muscle. In conclusion, we have identified novel proteasome inhibitors that qualify as potential candidates for pharmacological intervention in muscular dystrophy. — Briguet, A. , Erb, M. , Courdier‐Fruh, I. , Barzaghi, P., Santos, G. , Herzner, H. , Lescop, C. , Siendt, H. , Henneboehle, M. , Weyermann, P., Magyar, J. P., Dubach‐Powell, J., Metz, G. , Meier, T. Effect of calpain and proteasome inhibition on Ca2+‐dependent proteolysis and muscle histopathology in the mdx mouse. FASEB J. 22, 4190–4200 (2008)
Clinical studies of induction agents. XV. A comparison of the cumulative effects of thiopentone, methohexitone and propidid.

SUMMARY Thiopentone, methohexitone and propanidid have been given by intermittent dosage as main agent for a series of body surface operations. The requirements over the first hour show a marked falling off with the barbiturates but little decline with propanidid. This supports the experimental findings that propanidid is rapidly destroyed in the body whereas the other agents are translocated into storage depots.
Middle ear cholesteatoma: characteristic CT findings in 64 patients

BACKGROUND High resolution computerized tomography (HRCT) is valuable for detection of early erosive changes suggestive of cholesteatoma. The aim of our study was to determine characteristic CT findings in patients with middle ear cholesteatoma. METHODS We conducted a retrospective review of CT scans and surgical and histopathological reports in 64 patients with middle ear cholesteatoma (35 male, 29 female; age range, 7–80 years, median age, 22 years). CT scans were evaluated for the presence of intra-tympanic non-dependent soft tissue density, the extent of middle ear involvement, bone expansion and thinning, and bone erosions involving the ossicles and adjacent structures. RESULTS Middle ear cholesteatoma was more common in male patients and in patients aged 20–35 years. All patients had soft tissue density in the middle ear. Fifty-nine (92%) had expansion of the aditus and mastoid antrum, 59 (92%) had erosions of the ossicles, with involvement of the long process of the incus in 48 (75%), 55 (86%) had an eroded scutum, 55 (86%) an eroded facial nerve canal, 57 (89%) an eroded Koerner’s septum, which was totally destroyed in 19 (27%), 48 (75%) had tegmen erosion, and 63 (98%) had erosions of the antral walls. The correlation of pre-operative CT with surgical and histopathological findings was 97%. CONCLUSION Middle ear cholesteatoma is a distinct clinical entity with characteristic findings that may be suggested by CT imaging. These findings should alert the clinician to the possibility of cholesteatoma, which will guide in the surgical approach and treatment plan.
Atrial antitachycardia pacing: do we still need to talk about it?

Since first described in 1968,1 sick sinus syndrome (SSS) has become one of the most frequent indications for pacemaker implantation. Although in early days, the presence of atrial fibrillation (AF) limited the use of pacemakers in patients with SSS, nowadays pacemakers play an important role in the management of AF in patients with SSS. Highly sophisticated devices have been developed with increased Holter capabilities allowing continuous rhythm monitoring. Although the prevalence of AF prior to pacemaker implantation has been found in the range of 40–45%,2 AF detection during follow-up using pacemaker Holter data is reported in 50–65% of patients with SSS.3,4 In the Mode Selection Trial (MOST), pacemaker-detected paroxysmal AF was a strong independent predictor of stroke, death, and persistent AF, whereas symptoms as a clinical comparator could not reliably predict AF recurrence.4 The known limited success rate of drug therapy for rhythm control and the overwhelming number of pacemaker patients with paroxysmal AF prompted interest in using pacing therapy to treat AF. Therapy options developed included alternative single-site atrial pacing, multisite atrial pacing, pacing algorithms to prevent AF by increasing the amount of atrial pacing suppressing triggers of AF, and atrial antitachycardia pacing (ATP) to terminate AF. Many clinical trials have been conducted over the past 10 years studying the efficacy of pacing algorithms for AF prevention and termination. The present paper by Gillis et al. 5 reports the first long-term data on atrial ATP. Neither ATP alone nor ATP in combination with preventive pacing algorithms could successfully suppress atrial tachycardia (AT)/AF during a follow-up period of 3 years. The trial was early terminated due to phasing out of the AT500/501 pacemaker and study results may have been underpowered to detect any differences. However, the results correlate well with other ATP studies like … *Corresponding author. Tel: +49 89 9270 2071, Fax: +49 89 9270 2683, Email: ellen.hoffmann{at}klinikum-muenchen.de
Evaluation of Potential and Impedance Integrals in Analysis of Axially Symmetric Metallic Structures to Prescribed Accuracy Up To Machine Precision

This paper presents a novel method for evaluating potential and impedance integrals appearing in the method of moment analysis of arbitrary axially symmetric metallic structures based on exact wire kernel and higher order bases. Due to new variable transforms proposed for singularity cancellation and smoothing the integrands, high accuracy up to machine precision is achieved using relatively small number of integration points. Simple formulas are determined for predicting a number of integration points needed for prescribed accuracy. Benefits of high-precision evaluation of impedance integrals are illustrated on a number of numerical examples.
Bayesian Versus Frequentist Approach of the Frailty Cox Model, Application to Calf Gastroenteritis

In the frailty Cox model, frequentist approaches often present problems of numerical resolution, convergence, and variance calculation. The Bayesian approach offers an alternative. The goal of this study was to compare, using real (calf gastroenteritis) and simulated data, the results obtained with the MCMC method used in the Bayesian approach versus two frequentist approaches: the Newton–Raphson algorithm to solve a penalized likelihood and the EM algorithm. The results obtained showed that when the number of groups in the population decreases, the Bayesian approach gives a less biased estimation of the frailty variance and of the group fixed effect than the frequentist approaches.
First evidence of cryptic species diversity and significant population structure in a widespread freshwater nematode morphospecies (Tobrilus gracilis)

Free‐living nematodes are ubiquitous and highly abundant in terrestrial and aquatic environments, where they sustain ecosystem functioning by mineralization processes and nutrient cycling. Nevertheless, very little is known about their true diversity and intraspecific population structure. Recent molecular studies on marine nematodes indicated cryptic diversity and strong genetic differentiation of distinct populations, but for freshwater nematode species, analogous studies are lacking. Here, we present the first extensive molecular study exploring cryptic species diversity and genetic population structure of a widespread freshwater nematode morphospecies, Tobrilus gracilis, from nine postglacially formed European lakes. Taxonomic species status of individuals, analysed for fragments of the mitochondrial COI gene and for the large (LSU) and small (SSU) ribosomal subunits, were determined by morphological characteristics. Mitochondrial and nuclear markers strongly supported the existence of three distinct genetic lineages (Tg I–III) within Tobrilus gracilis, suggesting that this morphospecies indeed represents a complex of highly differentiated biological species. High genetic diversity was also observed at the population level. Across the nine lakes, 19 mitochondrial, and seven (LSU) and four (SSU) nuclear haplotypes were determined. A phylogeographical analysis revealed remarkable genetic differentiation even among neighbouring lake populations for one cryptic lineage. Priority and persistent founder effects are possible explanations for the observed population structure in the postglacially colonized lakes, but ask for future studies providing direct estimates of freshwater nematode dispersal rates. Our study suggests therefore that overall diversity of limnetic nematodes has been so far drastically underestimated and challenges the assumed ubiquitous distribution of other, single freshwater nematode morphospecies.
Short segments of Barrett’s epithelium and intestinal metaplasia in normal appearing oesophagogastric junctions: the same or two different entities?

Background—Endoscopic diagnosis of short segments of Barrett’s epithelium (SSBE) is difficult and its meaning in terms of the presence of specialised columnar epithelium (SCE) has not been prospectively evaluated. Aims—To evaluate the prevalence of SCE in patients with an endoscopic diagnosis of SSBE and in individuals with normal appearing oesophagogastric junctions, and to compare the clinical characteristics of these two groups. Patients—Thirty one patients with an endoscopic diagnosis of short Barrett’s oesophagus, less than 3 cm in length (group A), and 44 consecutive patients with normal appearing oesophagogastric junctions (group B). Methods—Multiple biopsies were performed in suspicious epithelium and at the oesophagogastric junction in groups A and B, respectively. Results—Age and sex distribution were similar in both groups. Reflux symptoms were more frequent in group A (p<0.001), as were endoscopic and histological signs of oesophagitis (p<0.0001 and p=0.001, respectively). SCE was found in 61.3% of group A patients compared with 25% in group B (p<0.002), with men predominating in group A while women were more frequent in group B (p=0.02). The differences in reflux symptoms and endoscopic/histological oesophagitis remained significant. Conclusions—These results show that endoscopic diagnosis of SSBE is associated with a high prevalence of SCE, significantly higher than that found in normal appearing oesophagogastric junctions. Differences between patients with SCE in the two groups suggest they may represent two different entities.
Basidiosporenentwicklung und ‐keimung bei Heterobasidiomyceten*

Zusammenfassung Die Art der Keimung von Basidiosporen und Sekundarsporen einiger Rostpilzarten wurde lichtoptisch untersucht. Das Kernverhalten wahrend der Keimung wurde mit Giemsa-Kernfarbung ermittelt. In Abhangigkeit vom Substrat werden Sekundarsporen, Suchhyphen und Infektionsstrukturen gebildet. Die Kernverhaltnisse wahrend der Keimung sind von auseren Einflussen abhangig. Dabei stehen Kernphasen und morphologische Keimungsdifferenzierungen in Beziehung zueinander. Schleudersporen werden im monokaryotischen Zustand gebildet, wobei sich der Kern teilt. Bei wiederholter Schleudersporenbildung wird jeweils ein Kern inaktiviert. Bei der Ausbildung von Suchhyphen oder Infektionsstrukturen bleibt die Kernzahl unverandert.
Nanoparticle Optimization for Enhanced Targeted Anticancer Drug Delivery.

Nanoparticle (NP)-based drug delivery is a promising method to increase the therapeutic index of anticancer agents with low median toxic dose. The delivery efficiency, corresponding to the fraction of the injected NPs that adhere to the tumor site, depends on NP size a and aspect ratio AR. Values for these variables are currently chosen empirically, which may not result in optimal targeted drug delivery. This study applies rigorous optimization to the design of NPs. A preliminary investigation revealed that delivery efficiency increases monotonically with a and AR. However, maximizing a and AR results in nonuniform drug distribution, which impairs tumor regression. Therefore, a multiobjective optimization (MO) problem is formulated to quantify the trade-off between NPs accumulation and distribution. The MO is solved using the derivative-free mesh adaptive direct search algorithm. Theoretically, the Pareto-optimal set consists of an infinite number of mathematically equivalent solutions to the MO problem. However, interesting design solutions can be identified subjectively, e.g., the ellipsoid with a major axis of 720 nm and an aspect ratio of 7.45, as the solution closest to the utopia point. The MO problem formulation is then extended to optimize NP biochemical properties: ligand-receptor binding affinity and ligand density. Optimizing physical and chemical properties simultaneously results in optimal designs with reduced NP sizes and thus enhanced cellular uptake. The presented study provides an insight into NP structures that have potential for producing desirable drug delivery.
Alterations in Connexin26 Expression during Colorectal Carcinogenesis

Background: Gap junctional intercellular communication (GJIC) is a mechanism for direct cell-to-cell signalling and is mediated by gap junctions, which consist of transmembrane proteins called connexins (Cxs). Human colorectal epithelial cells express Cx32 and Cx43. Methods: Tissue samples (152 from colorectal cancer and 75 from adenoma) were investigated by immunohistochemistry, using the antibody for Cx26. Moreover, Cx26 was assessed in normal epithelium of the colon and rectum, adjacent to colorectal cancer. Results: In normal epithelium and adenomas, intercellular, punctate staining for Cx26 was observed. In adenomas with severe dysplasia, focally decreased expression of Cx26 was observed. Among 152 colorectal cancers, 55.9% classified only as adenocarcinoma stained positive for Cx26, but mainly cytoplasmic staining was found. We observed a positive correlation between Cx26 expression and tumor G2 grade (p < 0.005). The expression of Cx26 did not correlate with age, sex of patients, tumor localization, lymph node status or tumor size. Conclusions: Our results show that during colorectal carcinogenesis, loss of normal intercellular Cx expression occurs. Furthermore, the cytoplasmic presence of Cx26 could indicate a different role of Cx26 in neoplastic cells than participation in GJIC.