Miracle-dz/UniFAR-FTUs huggingface dataset:
Individual profiling of circulating tumor cell composition and therapeutic outcome in patients with hepatocellular carcinoma.

BACKGROUND AND AIMS Circulating tumor cells (CTCs) have been proposed as a monitoring tool in patients with solid tumors. So far, automated approaches are challenged by the cellular heterogeneity of CTC, especially the epithelial-mesenchymal transition. Recently, Yu and colleagues showed that shifts in these cell populations correlated with response and progression, respectively, to chemotherapy in patients with breast cancer. In this study, we assessed which non-hematopoietic cell types were identifiable in the peripheral blood of hepatocellular carcinoma (HCC) patients and whether their distribution during treatment courses is associated with clinical characteristics. METHODS Subsequent to few enrichment steps, cell suspensions were spun onto glass slides and further characterized using multi-immunofluorescence staining. All non-hematopoietic cells were counted and individual cell profiles were analyzed per patient and treatment. RESULTS We detected a remarkable variation of cells with epithelial, mesenchymal, liver-specific, and mixed characteristics and different size ranges. The distribution of these subgroups varied significantly between different patient groups and was associated with therapeutic outcome. Kaplan-Meier log-rank test showed that a change in the ratio of epithelial to mesenchymal cells was associated with longer median time to progression (1 vs 15 months; P = .03; hazard ratio = 0.18; 95% confidence interval = 0.01-2.75). CONCLUSIONS Our data suggest that different CTC populations are identifiable in peripheral blood of HCC patients and, for the first time in HCC, that these individual cell type profiles may have distinct clinical implications. The further characterization and analysis of patients in this ongoing study seems to be warranted.
Electron Microscopic Evaluation of Adhesion of Helicobacter pylori to the Gastric Epithelial Cells in Chronic Gastritis

Background The adhesion of H. pylori to the gastric epithelial cells may be an essential step for the pathophysiology of various H. pylori-induced gastrointestinal diseases. The purpose of this study was to investigate the ultrastructural relation of H. pylori and gastric epithelial cells in their adhesion. Methods Endoscopic biopsy of gastric antrum and body was performed from 15 patients (9 men, 6 women) with chronic gastritis and H. pylori infection. The specimens were processed for electron microscopy and observed with a transmission electron microscope (Hitachi H-600). Results On the basis of morphological appearances, the adhesions of H. pylori to the gastric epithelial cells were categorized into three types; filamentous connection, adhesion pedestals and membrane fusion. Coccoid and undetermined forms adhered mainly by the filamentous connection, whereas the bacillary forms adhered primarily by the adhesion pedestals and membrane fusion. Conclusion Various types of adhesion were associated with H. pylori and gastric epithelium. Further studies are needed to evaluate the influence of different types of adhesion to the pathophysiology of H. pylori.
Prophylactic Mastectomy in BRCA1 and BRCA2 Mutation Carriers: Very Low Risk for Subsequent Breast Cancer

Aim:To examine the outcome of prophylactic mastectomy in a hospital-based series of BRCA1/2 gene mutation carriers with and without a history of breast cancer. Patients and Methods:A center-based consecutive series of 254 BRCA1/2 gene mutation carriers that had prophylactic mastectomy after a normal surveillance round including breast-magnetic resonance imaging were identified. One hundred forty-seven asymptomatic carriers underwent bilateral mastectomy and 107 symptomatic women had contralateral mastectomy after a mean cancer free interval of 3.6 years. All removed breasts were histopathologically examined. Results:In one asymptomatic BRCA2 carrier (0.7%) an occult small invasive breast cancer was diagnosed, while in 6 asymptomatic carriers (4.0% BRCA1 and 4.3% BRCA2) and in 5 symptomatic carriers (2.5% BRCA1 and 10.7% BRCA2) DCIS was detected at prophylactic mastectomy. No breast cancer occurred in the asymptomatic group after a postprophylactic follow-up period of 778 women-years. In the symptomatic carriers 1 invasive breast cancer was detected after 580 follow-up years. From age-, cohort-, and gene-specific reference data we calculated that 15 invasive first cancers in the asymptomatic carriers were prevented during follow-up. Conclusion:One invasive breast cancer in 147 bilateral prophylactic mastectomies (0.7%) was detected, this makes a sentinel node procedure redundant and preoperative imaging vital. The prophylactic procedure is highly effective in preventing invasive breast cancer in BRCA1/2 mutation carriers. Since the remaining risk is less than 0.2%/woman-year, continued surveillance of the asymptomatic carriers is not warranted.
Determination of In Situ Bacterial Growth Rates in Aquifers and Aquifer Sediments

ABSTRACT Laboratory and field-scale studies with stained cells were performed to monitor cell growth in groundwater systems. During cell division, the fluorescence intensity of the protein stain 5-(and 6-)-carboxyfluorescein diacetate succinimidyl ester (CFDA/SE) for each cell is halved, and the intensity can be tracked with a flow cytometer. Two strains of bacteria, Comamonas sp. strain DA001 and Acidovorax sp. strain OY-107, both isolated from a shallow aquifer, were utilized in this study. The change in the average generation or the average fluorescence intensity of the CFDA/SE-stained cells could be used to obtain estimates of doubling times. In microcosm experiments, the CFDA/SE-based doubling times were similar to the values calculated by total cell counting and were independent of cell concentration. Intact and repacked sediment core experiments with the same bacteria indicated that changes in groundwater chemistry were just as important as growth rates in determining planktonic cell concentrations. The growth rates within the sediment cores were similar to those calculated in microcosm experiments, and preferential transport of the daughter cells was not observed. The experiments indicated that the growth rates could be determined in systems with cell losses due to other phenomena, such as attachment to sediment or predation. Application of this growth rate estimation method to data from a field-scale bacterial transport experiment indicated that the doubling time was approximately 15 days, which is the first known direct determination of an in situ growth rate for bacteria in an aquifer.
Superior performance and Hot Carrier reliability of Strained FDSOI nMOSFETs for advanced CMOS technology nodes

The Hot Carrier (HC) reliability of NMOS transistors fabricated on biaxially tensile-strain SOI substrates (sSOI) is compared to that of devices fabricated on standard unstrained SOI substrates. It is shown that sSOI-based devices not only exhibit a 10% higher performance in term of ION/IOFF but also show superior HC reliability at same drive current. This reliability improvement may be explained by a better interface quality for sSOI films.
No increase in frequency of antifungal resistance among yeasts isolated from normally sterile sites in patients at Foothills Hospital from 1993 to 1996.

OBJECTIVE To determine the prevalence of resistance to antifungal drugs among yeasts isolated from sterile sites from patients in one hospital and the relationship of resistance to antifungal use, and to assess whether resistance was increasing. METHOD Susceptibility testing performed by National Committee for Clinical Laboratory Standards (NCCLS) (Villanova, Pennsylvania) microdilution method and by E test. Antifungal use was determined by selected chart review and from pharmacy data. SPECIMENS AND SETTING: Tertiary care adult hospital with neonatal intensive care. POPULATION STUDIED Distinct yeast isolates from sterile site specimens collected during the years 1993 to 1996. RESULTS A total of 132 yeast isolates were studied, of which 78 (59%) were Candida albicans. The proportion of C albicans remained steady over the four-year period, and there was no trend to increased resistance among C albicans. The number of isolates of all species with fluconazole microdilution minimum inhibitory concentration (MIC) greater than 8 mg/L in each of the four years were one of 32 in 1996, three of 26 in 1994, six of 33 in 1995, and one of 41 in 1996. A single isolate had an itraconazole microdilution MIC greater than 0.5 mg/L in each year. Prior use of antifungal therapy was rare in this patient population. CONCLUSIONS The increase in resistance to antifungal drugs reported by some centres did not occur in this institution over the course of the study. This experience may reflect differences in infection control practices and in patterns of use of antifungal agents. The NCCLS method was found to be superior to the E test as a routine method for testing susceptibility of yeasts.
Perseverative Writing Errors in a Patient with Alzheimer's Disease

This study reports the writing performance of a dysgraphic patient with Alzheimer's disease and moderate dementia who frequently perseverated on strokes and letters. Letter formation errors were also frequently produced. Oral spelling was superior to written spelling. The habitual style of writing (cursive writing) was significantly more prone to perseverations than writing in uppercase letters, a form of writing less frequently used by the patient. Central (linguistic) spelling processes were relatively preserved. The pattern of preserved and impaired functions is consistent with impairment of the peripheral mechanism that generates the graphic motor patterns code. We suggest that damage to the peripheral orthographic mechanism may cause deficits in some patients with Alzheimer's disease.
Investor Types and Stock Return Volatility

The purpose of this paper is twofold: investigate how different types of investors affect stock return volatility, and provide some explanations based on investors’ trading behavior. Norway provides an excellent setting with monthly holding data of all investors on all listed firms over a period of 15 years. The results show that foreign investors increase stock return volatility because they trade the most, are momentum traders, and have the shortest investment horizon. In contrast, individual investors reduce stock return volatility because they trade the least, are contrarian traders, and have the longest investment horizon. Domestic institutional investors fall in-between these extremes.
Central adrenergic neurons in DOCA‐salt hypertension

The effects of various doses of 6‐hydroxydopamine(6‐OHDA) injected into the hypothalamus on DOCA‐salt‐induced hypertension were studied. The development of hypertension was prevented in the group treated with the highest dose of 6‐OHDA, and the onset of hypertension was delayed in a dose‐dependent fashion in the groups treated with the lower doses of 6‐OHDA. Catecholamine histofluorescence observations showed that the cannula tips placed the drug lateral to the third ventricle. The most prominent change observed was a marked unilateral reduction in the fluorescence of the dopaminergic nerves of the caudate‐putamen and in the number of cell bodies in the substantia nigra. These results suggest possible sites of central aminergic control of blood pressure.
Strain fields and line energies of dislocations in uranium dioxide

Computer simulations are used to investigate the stability of typical dislocations in uranium dioxide. We explain in detail the methods used to produce the dislocation configurations and calculate the line energy and Peierls barrier for pure edge and screw dislocations with the shortest Burgers vector . The easiest slip system is found to be the {100}⟨110⟩ system for stoichiometric UO2, in agreement with experimental observations. We also examine the different strain fields associated with these line defects and the close agreement between the strain field predicted by atomic scale models and the application of elastic theory. Molecular dynamics simulations are used to investigate the processes of slip that may occur for the three different edge dislocation geometries and nudged elastic band calculations are used to establish a value for the Peierls barrier, showing the possible utility of the method in investigating both thermodynamic average behaviour and dynamic processes such as creep and plastic deformation.
Connecting empowerment-focused HRM and labour productivity to work engagement: the mediating role of job demands and resources

Integrating the strategic HRM literature with key aspects of the job demands-resources (JDR) model, we propose in this study that empowerment-focused HRM and labour productivity influence work engagement of employees by shaping task-related resources and demands. A total of 311 employees nested within 46 work units of a general hospital rated their task-related resources, demands and work engagement. The line managers from these work units rated the implemented empowerment-focused HR practices in, and the relative labour productivity of, their work unit. Results indicate that job variety positively mediates the influence of empowerment-focused HRM on work engagement. In addition, job demands negatively mediate the influence of labour productivity on work engagement. The findings shed light on the way empowerment-focused HRM and labour productivity influence work engagement and highlight the importance of taking into account key aspects of the JDR model (job demands and resources for employees during work) as mediating mechanisms.
Validity and Reliability of Turkish Translation of Migraine Disability Assessment (MIDAS) Questionnaire in Patients with Migraine

The Migraine Disability Assessment (MIDAS) questionnaire is a brief, self-administered questionnaire which is designed to quantify headache-related disability in a 3-month period. We have tested a Turkish version of the MIDAS questionnaire in 60 migraine patients. Sixty of the clinically diagnosed migraine headache sufferers were enrolled in a 90-day diary study and completed the MIDAS questionnaire in the first, 21st and the last day of the 90-day study. The scores taken from the diary and the scores of the MIDAS taken at different times were evaluated by the correlation tests of both Pearson and Spearman for each question and total scores. Cronbach's scores taken from the diary and taken from the test of the MIDAS which was applied at different times were evaluated. Pearson's correlation on the responses in the initial MIDAS questions was between 0.44 (reduced productivity in household chores) and 0.78 (missed work or school days). The correlation of the Spearman was similar to the Pearson values. As a result, we found that the overall score of the MIDAS has a good reliability and its internal consistency is also good (Cronbach's α 0.87). These findings support the use of the MIDAS questionnaire as a clinical and research tool on Turkish patients.
Rituximab for remission induction and maintenance in refractory granulomatosis with polyangiitis (Wegener's): ten-year experience at a single center.

OBJECTIVE This study was conducted to evaluate the efficacy and safety of repeated and prolonged B cell depletion with rituximab (RTX) for the maintenance of long-term remission in patients with chronic relapsing granulomatosis with polyangiitis (Wegener's) (GPA). METHODS We conducted a single-center observational study of all patients with chronic relapsing GPA treated with at least 2 courses of RTX between January 1, 2000 and May 31, 2010. Participants in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial were excluded from this analysis. Data were abstracted from electronic medical records. RESULTS Fifty-three patients with refractory GPA (median age 46 years [interquartile range (IQR) 30-61 years]; 53% women) received at least 2 courses of RTX to treat GPA relapses or to maintain remission. All but 1 patient had antineutrophil cytoplasmic antibodies (ANCA) against proteinase 3 (PR3). These patients received a median of 4 courses of RTX (IQR 3-5); all had depletion of B cells, and the median time to return of B cells was 8.5 months (IQR 6-11 months). All observed relapses occurred after reconstitution of B cells and were accompanied or preceded by an increase in ANCA levels, except for the 1 ANCA-negative patient. Infusion-related adverse events occurred in 16 patients. During the period of B cell depletion, 30 infections requiring antimicrobial therapy were recorded. CONCLUSION RTX appeared to be effective and safe for the induction and maintenance of remission in patients with chronic relapsing GPA. Repeated depletion of B lymphocytes seems to be associated with a low risk of infections. Preemptive re-treatment decisions can be individualized based on serial B lymphocyte and PR3 ANCA monitoring. The use of RTX for the maintenance of long-term remission merits further formal investigation.
Mechanisms of quinolone resistance in Escherichia coli: characterization of nfxB and cfxB, two mutant resistance loci decreasing norfloxacin accumulation

Two genetic loci selected for norfloxacin (nfxB) and ciprofloxacin (cfxB) resistance were characterized. Both mutations have previously been shown to confer pleiotropic resistance to quinolones, chloramphenicol, and tetracycline and to decrease expression of porin outer-membrane protein OmpF. nfxB was shown to map at about 19 min and thus to be genetically distinct from ompF (21 min), and cfxB was shown to be very closely linked to marA (34 min). cfxB was dominant over cfxB+ in merodiploids, in contrast to other quinolone resistance mutations. The two loci appear to interact functionally, because nfxB was not expressed in the presence of marA::Tn5. Both nfxB and cfxB decreased the expression of ompF up to 50-fold at the posttranscriptional level as determined in strains containing ompF-lacZ operon and protein fusions. Both mutations also decreased norfloxacin accumulation in intact cells. This decrease in accumulation was abolished by energy inhibitors and by removal of the outer membrane. These findings, in conjunction with those of Cohen et al. (S. P. Cohen, D. C. Hooper, J. S. Wolfson, K. S. Souza, L. M. McMurry, and S. B. Levy, Antimicrob. Agents Chemother. 32:1187-1191, 1988), suggest a model for quinolone resistance by decreased permeation in which decreased diffusion through porin channels in the outer membrane interacts with a saturable drug efflux system at the inner membrane.
Does intrathymic injection of alloantigen‐presenting cells before islet allo‐transplantation prolong graft survival?

Abstract Current immunosuppressive agents have potentially dangerous side‐effects, are nonspecific and most are also diabetogenic. We investigated tolerance induction with intrathymic injection of purified antigen‐presenting cells (APC) plus a single dose of anti‐lymphocyte serum (ALS) intraperitoneally before allogeneic islet transplantation in the rat model WAG to Lewis (RT1u to RT11. Purified donor APC [non‐parenchymal cells (NPC) or dendritic cells (DC)] were prepared from liver and spleen, respectively. Isograft function for more than 120 days proved that islet isolation, purification and transplantation procedures were adequate. A total of WAG DC (4 times 105) or NPC (2 times 106) in 20 μl were injected into both lobes of the thymus of 140–210 g Lewis recipients followed by a single injection of ALS. Three days later, diabetes was induced with streptozotocin (60 mg/kg). Four days later allogeneic islets were grafted into the liver by intraportal injection of 3000 WAG islets. Control animals (n= 8) received 20 μ saline intrathymically instead of APC. Graft function was assessed by blood glucose measurements with glucose levels above 15 mmol/l on 3 consecutive days defined as graft rejection. Animals given DC (n= 9) or NPC (n= 8) intrathymically plus 1 ml of ALS, rejected their grafts in an accelerated fashion with a median survival time (MST) of 3 days. However, control animals rejected their grafts with a MST of 7 days, but with two animals surviving for more than 2 months. In conclusion, intrathymic inoculation with purified APC plus a single dose of ALS did not prolong allogeneic islet graft function but induce? accelerated rejection of the islet allografts.
Effective knowledge‐based potentials

Empirical or knowledge‐based potentials have many applications in structural biology such as the prediction of protein structure, protein–protein, and protein–ligand interactions and in the evaluation of stability for mutant proteins, the assessment of errors in experimentally solved structures, and the design of new proteins. Here, we describe a simple procedure to derive and use pairwise distance‐dependent potentials that rely on the definition of effective atomic interactions, which attempt to capture interactions that are more likely to be physically relevant. Based on a difficult benchmark test composed of proteins with different secondary structure composition and representing many different folds, we show that the use of effective atomic interactions significantly improves the performance of potentials at discriminating between native and near‐native conformations. We also found that, in agreement with previous reports, the potentials derived from the observed effective atomic interactions in native protein structures contain a larger amount of mutual information. A detailed analysis of the effective energy functions shows that atom connectivity effects, which mostly arise when deriving the potential by the incorporation of those indirect atomic interactions occurring beyond the first atomic shell, are clearly filtered out. The shape of the energy functions for direct atomic interactions representing hydrogen bonding and disulfide and salt bridges formation is almost unaffected when effective interactions are taken into account. On the contrary, the shape of the energy functions for indirect atom interactions (i.e., those describing the interaction between two atoms bound to a direct interacting pair) is clearly different when effective interactions are considered. Effective energy functions for indirect interacting atom pairs are not influenced by the shape or the energy minimum observed for the corresponding direct interacting atom pair. Our results suggest that the dependency between the signals in different energy functions is a key aspect that need to be addressed when empirical energy functions are derived and used, and also highlight the importance of additivity assumptions in the use of potential energy functions.
Determinants of Generic Substitution in the Czech Republic

Using individual level-data, the paper uncovers patient and drug characteristics that determine the probability of using the original patented products despite the presence of generic substitutes in the Czech Republic in the period 2009-2013. Our results reveal different behavioral patterns for drugs against acute and chronic diseases. The results have direct implications for the design of pharmaceutical policies aiming at an increased consumption of generic substitutes.
Diffusion and volumetry abnormalities in subcortical nuclei of patients with absence seizures

Purpose: The thalamus and basal ganglia play an important role in the propagation and modulation of generalized spike and slow‐wave discharges (SWDs) in absence epilepsy. Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique sensitive to microstructural abnormalities of cerebral tissue by quantification of diffusion parameter. The purpose of this study is to investigate the diffusion and volume changes in the basal ganglia and thalamus of patients with absence seizures.