Miracle-dz/UniFAR-FTUs huggingface dataset:
Diffuse Large B-cell Lymphoma Arising in Nodular Lymphocyte Predominant Hodgkin Lymphoma. A Report of 21 Cases from the Nebraska Lymphoma Study Group

We sought to investigate the clinical characteristics and pathologic features and survival outcome of patients with diffuse large B-cell lymphoma (DLBCL) arising in nodular lymphocyte predominant Hodgkin's disease (NLPHL), since controversy regarding their prognosis exists in the literature. Twenty-one patients with DLBCL arising either concurrently with <formula>(<italic>n</italic>=7)</formula> or subsequent to <formula>(<italic>n</italic>=14)</formula> a diagnosis of NLPHL were identified in the Nebraska Lymphoma Study Group Registry. The clinical and pathologic features of the cases were evaluated, and survival analysis was performed from the time of diagnosis of DLBCL. The median time to the development of DLBCL in those with prior NLPHL was only one year (range, 0.5-24 years). The median age of the patients at the time of diagnosis of DLBCL was 46 years (range, 18-72 years) and the male to female ratio was 17:4. Ten patients presented with nodal DLBCL only, six patients presented with both nodal and extranodal involvement, and five patients presented with only extranodal DLBCL. Eleven patients had limited stage (I/II) disease and 10 had advanced stage (III/IV) disease. The median overall survival (OS) and failure-free survival (FFS) of the entire group was 35 months and 11 months, respectively, and the predicted five-year OS and FFS was 31 and 18%, respectively. There were no significant differences in the survival outcomes between patients with DLBCL arising in NLPHL and age- and sex- matched patients with de novo DLBCL. In conclusion, our findings suggest that patients with DLBCL arising in NLPHL have a prognosis similar to those with de novo DLBCL and should be treated aggressively.
Changes in the Histone Acetylation Patterns during the Development of the Nervous System

Epigenetic modification such as DNA methylation and histone acetylation plays essential roles in many aspects of cellular function and development of animals. There is an increasing amounts of evidence for dynamic changes in the histone acetylation of specific gene segments, but little attempt was made to examine global pattern changes in the histone acetylation in developing nervous system. In this study, we found that acetylated histone H3 and H4 immunoreactivities were relatively weak in neuroepithelial cells in the ventricular zone of developing rat cerebral cortex or chick spinal cord, compared to the immature young neurons in the cortical plate of a rat embryo or lateral motor column in chick spinal cord. On the other hand, adult neural stem cells in the dentate gyrus (DG) of rat hippocampal formation did not exhibit such diminished histone acetylation, compared to neuroblasts and mature DG neurons. These results suggest that the level of histone acetylation is highly dynamic and tightly linked to the neuronal types and the differentiation stages.
Plasma Endothelin Correlates With the Extent of Pulmonary Hypertension in Patients With Chronic Congestive Heart Failure

BackgroundEndothelin is a family of potent vasoconstrictor peptides of vascular endothelial origin. Although it has been proposed that the vasoconstrictor effects of endothelin are produced at the local vascular level, increased plasma concentration of endothelin has been identified in cardiovascular disorders. Methods and ResultsWe tested whether immunoreactive endothelin-1 could be detected by radioimmunoassay in plasma of congestive heart failure patients and whether levels correlated with hemodynamic characteristics. Twenty congestive heart failure patients (New York Heart Association class II-IV) were sampled in the morning after an overnight fast, before medication. Cardiac index was decreased to 2.14±0.45 l/m/m2, and pulmonary wedge pressure was increased to 22±7 mm Hg. The ranges of pulmonary pressures were: systolic, 22–100 mm Hg, mean, 13–61 mm Hg, and diastolic, 8–42 mm Hg. The endothelin-1 level was 9.07±4.13 pg/ml (range, 4–19 pg/ml), which was increased compared with 12 normals (3.7±0.6 pg/ml; range, 2.8–4.7 pg/ml); the difference was statistically significant (p<0.0001). Endothelin- 1 significantly correlated with pulmonary pressures (systolic, r=0.78; mean, r=0.80; diastolic, r=0.77; all p<0.003) and pulmonary vascular resistance (r=0.65, p<0.01). Endothelin- 1 strongly correlated with the resistance ratio (pulmonary vascular resistance/systemic vascular resistance) (r=0.88, p<0.0001). Stepwise multiple regression analysis confirmed the significance of these observations. ConclusionsElevated immunoreactive endothelin-1 specifically correlated with the extent of pulmonary hypertension in congestive heart failure patients. Whether endothelin-1 is a regional mediator of pulmonary hypertension or a marker for its occurrence requires additional evaluation.
Intrinsic brain connectivity in fibromyalgia is associated with chronic pain intensity.

OBJECTIVE Fibromyalgia (FM) is considered to be the prototypical central chronic pain syndrome and is associated with widespread pain that fluctuates spontaneously. Multiple studies have demonstrated altered brain activity in these patients. The objective of this study was to investigate the degree of connectivity between multiple brain networks in patients with FM, as well as how activity in these networks correlates with the level of spontaneous pain. METHODS Resting-state functional magnetic resonance imaging (FMRI) data from 18 patients with FM and 18 age-matched healthy control subjects were analyzed using dual-regression independent components analysis, which is a data-driven approach for the identification of independent brain networks. Intrinsic, or resting-state, connectivity was evaluated in multiple brain networks: the default mode network (DMN), the executive attention network (EAN), and the medial visual network (MVN), with the MVN serving as a negative control. Spontaneous pain levels were also analyzed for covariance with intrinsic connectivity. RESULTS Patients with FM had greater connectivity within the DMN and right EAN (corrected P [P(corr)] < 0.05 versus controls), and greater connectivity between the DMN and the insular cortex, which is a brain region known to process evoked pain. Furthermore, greater intensity of spontaneous pain at the time of the FMRI scan correlated with greater intrinsic connectivity between the insula and both the DMN and right EAN (P(corr) < 0.05). CONCLUSION These findings indicate that resting brain activity within multiple networks is associated with spontaneous clinical pain in patients with FM. These findings may also have broader implications for how subjective experiences such as pain arise from a complex interplay among multiple brain networks.
The heat shock transcription factor Hsf1 is downregulated in DNA damage–associated senescence, contributing to the maintenance of senescence phenotype

Heat shock response (HSR) that protects cells from proteotoxic stresses is downregulated in aging, as well as upon replicative senescence of cells in culture. Here we demonstrate that HSR is suppressed in fibroblasts from the patients with segmental progerioid Werner Syndrome, which undergo premature senescence. Similar suppression of HSR was seen in normal fibroblasts, which underwent senescence in response to DNA damaging treatments. The major DNA‐damage‐induced signaling (DDS) pathways p53–p21 and p38‐NF‐kB‐SASP contributed to the HSR suppression. The HSR suppression was associated with inhibition of both activity and transcription of the heat shock transcription factor Hsf1. This inhibition in large part resulted from the downregulation of SIRT1, which in turn was because of decrease in the expression of the translation regulator HuR. Importantly, we uncovered a positive feedback regulation, where suppression of Hsf1 further activates the p38–NF‐κB‐SASP pathway, which in turn promotes senescence. Overexpression of Hsf1 inhibited the p38–NFκB‐SASP pathway and partially relieved senescence. Therefore, downregulation of Hsf1 plays an important role in the development or in the maintenance of DNA damage signaling‐induced cell senescence.
Characterization of the native honey bee subspecies in Saudi Arabia using the mtDNA COI-COII intergenic region and morphometric characteristics.

Morphometric and genetic markers are very common and powerful tools used to characterize honey bee subspecies. In Saudi Arabia, morphometric analysis using 24 characteristics separated the Saudi honey bee between two reference subspecies. Most Saudi honey bee samples clustered with Apis mellifera jemenitica reference group, but others were more similar to Apis mellifera litorea reference group. Based on sequence analysis of the mtDNA COI–COII region, 18 new and clearly separated haplotypes were characterized for the first time. Sequence analyses showed that most haplotypes belonged to the O lineage and are very close to the Syrian haplotypes found in the gene databank (NCBI). However, two other haplotypes belonged to the A lineage and are clearly different from the Ethiopian haplotypes previously described as A.m. jemenitica. However, no previous genetic data for the A.m. jemenitica from Saudi Arabia, Yemen or Oman are available in the databank for comparison purposes. Additionally, this high genetic diversity in the mtDNA COI–COII region and the clear morphometric variation suggest that the honey bee of Saudi Arabia represents more than one distinct honey bee subspecies.
Nuclear localization of barrier-to-autointegration factor is correlated with progression of S phase in human cells

Barrier-to-autointegration factor (BAF) is a conserved metazoan protein that plays a critical role in retrovirus infection. To elucidate its role in uninfected cells, we first examined the localization of BAF in both mortal and immortal or cancerous human cell lines. In mortal cell lines (e.g. TIG-1, WI-38 and IMR-90 cells) BAF localization depended on the age of the cell, localizing primarily in the nucleus of >90% of young proliferating cells but only 20-25% of aged senescent cells. In immortal cell lines (e.g. HeLa, SiHa and HT1080 cells) BAF showed heterogeneous localization between the nucleus and cytoplasm. This heterogeneity was lost when the cells were synchronized in S phase. In S-phase-synchronized populations, the percentage of cells with predominantly nuclear BAF increased from 30% (asynchronous controls) to ∼80%. In HeLa cells, RNAi-induced downregulation of BAF significantly increased the proportion of early S-phase cells that retained high levels of cyclin D3 and cyclin E expression and slowed progression through early S phase. BAF downregulation also caused lamin A to mislocalize away from the nuclear envelope. These results indicate that BAF is required for the integrity of the nuclear lamina and normal progression of S phase in human cells.
Improved subspace DoA estimation methods with large arrays: The deterministic signals case

This paper is devoted to the subspace DoA estimation using a large antennas array when the number of available snapshots is of the same order of magnitude than the number of sensors. In this context, the traditional subspace methods fail because the empirical covariance matrix of the observations is a poor estimate of the true covariance matrix. Mestre et al. proposed recently to study the behaviour of the traditional estimators when the number of antennas M and the number of snapshots N converge to +∞ at the same rate. Using large random matrix theory results, they showed that the traditional subspace estimate is not consistent in the above asymptotic regime and they proposed a new consistent subspace estimate which outperforms the standard subspace method for realistic values of M and N. However, the work of Mestre et al. assumes that the source signals are independent and identically distributed in the time domain. The goal of the present paper is to propose new consistent estimators of the DoAs in the case where the source signals are modelled as unknown deterministic signals. This, in practice, allows to use the proposed approach whatever the statistical properties of the source signals are.
Substrate Profiling of Tobacco Etch Virus Protease Using a Novel Fluorescence-Assisted Whole-Cell Assay

Site-specific proteolysis of proteins plays an important role in many cellular functions and is often key to the virulence of infectious organisms. Efficient methods for characterization of proteases and their substrates will therefore help us understand these fundamental processes and thereby hopefully point towards new therapeutic strategies. Here, a novel whole-cell in vivo method was used to investigate the substrate preference of the sequence specific tobacco etch virus protease (TEVp). The assay, which utilizes protease-mediated intracellular rescue of genetically encoded short-lived fluorescent substrate reporters to enhance the fluorescence of the entire cell, allowed subtle differences in the processing efficiency of closely related substrate peptides to be detected. Quantitative screening of large combinatorial substrate libraries, through flow cytometry analysis and cell sorting, enabled identification of optimal substrates for TEVp. The peptide, ENLYFQG, identical to the protease's natural substrate peptide, emerged as a strong consensus cleavage sequence, and position P3 (tyrosine, Y) and P1 (glutamine, Q) within the substrate peptide were confirmed as being the most important specificity determinants. In position P1′, glycine (G), serine (S), cysteine (C), alanine (A) and arginine (R) were among the most prevalent residues observed, all known to generate functional TEVp substrates and largely in line with other published studies stating that there is a strong preference for short aliphatic residues in this position. Interestingly, given the complex hydrogen-bonding network that the P6 glutamate (E) is engaged in within the substrate-enzyme complex, an unexpectedly relaxed residue preference was revealed for this position, which has not been reported earlier. Thus, in the light of our results, we believe that our assay, besides enabling protease substrate profiling, also may serve as a highly competitive platform for directed evolution of proteases and their substrates.
Assessing the Levels and Health Risk of Atmospheric Formaldehyde in Makkah, Saudi Arabia

Atmospheric Formaldehyde (HCHO) was monitored in four sites on the Holy Mosque of Makkah, Saudi Arabia during August, 2013. The daily mean concentrations of HCHO were ranged from 1.09-18.92 μg/m. The levels of HCHO were significantly higher than the permissible exposure limit (0.042 μg/m) of the Occupational Safety and Health Administration (OSHA). However, it were not exceeded the recommended exposure limit of the National Institute for Occupational Safety and Health (20 μg/m) and Egyptian law 4/1994 (0.37 mg/m). Spatial variations of HCHO concentrations most probably due to variations in local meteorology and traffic flow, which was considered the main source of emissions. Exposure doses for various age groups were estimated, which ranged from 0.000004 to 0.000259 mg/kg/day. Maximum exposure dose was recorded for boys (age 12-14 years) and children (6-8 years) and minimum for females (19-65 years).
Acute adult cervical pyogenic discitis with neurological deterioration treated by antibiotics

Acute adult primary cervical pyogenic spondylodiscitis and discitis are usually treated with surgery and antibiotics, particularly for cases demonstrating neurological deficit. Here we report a case of acute adult primary cervical pyogenic discitis with the formation of epidural abscess treated with antibiotics alone. A 36-year-old male presented with neck and bilateral upper limb pain for 6 days. Physical examination showed evident nuchal rigidity and tenderness in the neck, and slight bilateral upper limb weakness. Laboratory findings revealed elevated white blood cell count, erythrocyte sedimentation rate and C-reactive protein level. Magnetic resonance imaging revealed epidural abscess extending from C4 to C6, resulting in anterior compression of the spinal cord. Blood culture detected Staphylococcus aureus. Although the disease had progressed and upper limb weakness was aggravated, only antibiotics without surgery were administered. The patient’s pain eased and body temperature, WBC count, ESR, and CRP normalized after antibiotics were administered intravenously. He was discharged after 3 weeks of antibiotic therapy. A follow-up MRI showed that the abscess had been absorbed completely, and no recurrence of discitis was found. In conclusion, cervical pyogenic discitis is a rare spinal infection and antibiotics can be effective in treating this disease, even if compression caused by epidural abscess leads to a neurological deficit.
Effect of dialyser membrane pore size on plasma homocysteine levels in haemodialysis patients.

BACKGROUND Hyperhomocysteinaemia is a putative risk factor for atherothrombotic cardiovascular disease in the haemodialysis population. High-dose vitamin B therapy does not entirely normalize elevated plasma total homocysteine (tHcy) levels in haemodialysis patients. Alternative therapies to reduce tHcy further are therefore required. Modifications of the dialysis regimen may result in a better removal of Hcy. We examined the effect of dialyser membrane pore size on tHcy levels in vitamin-replete chronic haemodialysis patients. METHODS Forty-five haemodialysis patients were dialysed during 4 weeks with a low-flux, a high-flux and a super-flux membrane, in random order. Pre-dialysis tHcy was determined at baseline and every 4 weeks. In 18 patients, plasma tHcy before and after dialysis and dialysate tHcy concentrations were measured. RESULTS Pre-dialysis tHcy decreased significantly during 4 weeks super-flux dialysis (-14.6 +/- 2.8%), whereas it remained stable during high-flux (+0.5 +/- 2.4%) and low-flux dialysis (+1.7 +/- 3.2%). The homocysteine reduction ratio was not different for the three membranes: 0.39 +/- 0.03 for the super-flux, 0.47 +/- 0.02 for the high-flux and 0.39 +/- 0.02 for the low-flux dialyser. The amount of Hcy recovered in the dialysate during a single dialysis session was also similar: 117.5 +/- 3.6 micro mol during super-flux, 95.3 +/- 11.5 micro mol during high-flux and 116.5 +/- 11.6 micro mol during low-flux dialysis. CONCLUSION Super-flux dialysis significantly lowers tHcy in chronic haemodialysis patients. Improved removal of middle-molecule uraemic toxins with inhibitory effects on Hcy-metabolizing enzymes, rather than better dialytic clearance of Hcy itself, may explain the beneficial effect of the super-flux membrane.
The safety and efficacy of amphotericin B colloidal dispersion in the treatment of invasive mycoses.

Amphotericin B colloidal dispersion (ABCD), a novel formulation of amphotericin B and cholesteryl sulfate in a 1:1 ratio, was developed to reduce the toxicity of amphotericin B yet retain its antifungal efficacy. In an open-label trial, ABCD at dosages as high as 6 mg/(kg.d) was administered to 168 patients with documented or presumed systemic mycoses. All patients had responded incompletely to at least 7 days' treatment with conventional amphotericin B (CAB), had experienced CAB-induced nephrotoxic effects, had preexisting renal impairment, or had experienced other CAB-related, treatment-limiting toxic effects. The clinical response to ABCD could be evaluated in 97 patients. Complete clinical response or improvement was noted in 48 (49%) of them after a mean treatment duration of 18.5 days. All 168 enrolled patients were evaluated with regard to safety of the treatment. Even at daily doses as high as 6 mg/kg, and mean and median cumulative doses of 4.0 g and 2.4 g, respectively, ABCD had little renal toxicity: the mean change in serum level of creatinine from baseline to final value was -0.02 mg/dL. Hypokalemia developed in eight patients (5%). This study provides preliminary evidence that ABCD is effective in treating invasive mycoses and lacks the dose-limiting nephrotoxicity of CAB.
International Journal of Hospitality Management Examining the Determinants of Hotel Chain Expansion through International Franchising

This study proposes and tests an agency-based organizational model of internationalization through franchising in the hotel sector. Using data obtained from a Franchisor Questionnaire 2001–2008, we analyzed a panel of 117 observations of 17 U.S.-based hotels. Our analysis reveals that a hotel franchisor's decision to internationalize through franchising is positively related to the percentage of franchises, the ratio of franchised units to the total number of units. The article contributes to the literature by empirically modeling international franchising of hotels, which present unique characteristics among franchising companies, with a high investment capital requirement, maturity in the product life cycle, and a high level of standardization and globalization of operations. The unique characteristics of individual chains and their segment in the industry are particularly important, as revealed by both data analysis and expert opinion.
Topologically Sorted Skylines for Partially Ordered Domains

The vast majority of work on skyline queries considers totally ordered domains, whereas in many applications some attributes are partially ordered, as for instance, domains of set values, hierarchies, intervals and preferences. The only work addressing this issue has limited progressiveness and pruning ability, and it is only applicable to static skylines. This paper overcomes these problems with the following contributions. (i) We introduce a generic framework, termed TSS, for handling partially ordered domains using topological sorting. (ii) We propose a novel dominance check that eliminates false hits/misses, further enhancing progressiveness and pruning ability. (iii) We extend our methodology to dynamic skylines with respect to an input query. In this case, the dominance relationships change according to the query specification, and their computation is rather complex. We perform an extensive experimental evaluation demonstrating that TSS is up to 9 times and up to 2 orders of magnitude faster than existing methods in the static and the dynamic case, respectively.
Dissociable Perceptual Effects of Visual Adaptation

Neurons in the visual cortex are responsive to the presentation of oriented and curved line segments, which are thought to act as primitives for the visual processing of shapes and objects. Prolonged adaptation to such stimuli gives rise to two related perceptual effects: a slow change in the appearance of the adapting stimulus (perceptual drift), and the distortion of subsequently presented test stimuli (adaptational aftereffects). Here we used a psychophysical nulling technique to dissociate and quantify these two classical observations in order to examine their underlying mechanisms and their relationship to one another. In agreement with previous work, we found that during adaptation horizontal and vertical straight lines serve as attractors for perceived orientation and curvature. However, the rate of perceptual drift for different stimuli was not predictive of the corresponding aftereffect magnitudes, indicating that the two perceptual effects are governed by distinct neural processes. Finally, the rate of perceptual drift for curved line segments did not depend on the spatial scale of the stimulus, suggesting that its mechanisms lie outside strictly retinotopic processing stages. These findings provide new evidence that the visual system relies on statistically salient intrinsic reference stimuli for the processing of visual patterns, and point to perceptual drift as an experimental window for studying the mechanisms of visual perception.