Miracle-dz/UniFAR-FTUs huggingface dataset:
Outcome of patients with relapsed/refractory acquired immune deficiency syndrome-related lymphoma diagnosed 1999–2008 and treated with curative intent in the AIDS Malignancy Consortium

Abstract No comparative studies exist for relapsed/refractory (rel/rfr) acquired immune deficiency syndrome (AIDS)-related lymphoma (ARL). To determine practices over the last decade and to assess the outcomes of salvage chemotherapy with curative intent and autologous stem cell transplant (ASCT), we retrospectively evaluated treatment outcomes in patients with rel/rfr ARL who were treated in 13 national AIDS Malignancy Consortium (AMC) sites between 1999 and 2008 (n = 88). The most commonly used second-line therapies were ICE (ifosfamide/carboplatin/etoposide, n = 34), dose adjusted EPOCH (etoposide/prednisone/vincristine/cyclophosphamide/doxorubicin, n = 17) and ESHAP (etoposide/methylprednisolone/cytarabine/cisplatin, n = 11). The odds of achieving a response were lower for those with non-Hodgkin lymphoma (NHL) than for those with HL and for those with primary refractory disease than for those with relapse. Overall survival (OS) was significantly longer for those with relapsed disease compared to those with refractory disease and for those with non-Burkitt NHL compared to those with Burkitt. OS was longer in patients who underwent ASCT compared to those who did not (1-year OS: 63.2% vs. 37.2%). However, among 32 patients (36%) who achieved a complete or partial reponse (CR/PR) after second-line therapy, 1-year OS was not different between the two groups (87.5% for ASCT vs. 81.8% for non-ASCT). Long-term survival in some patients with rel/rfr ARL may be possible without transplant, although transplant remains the standard of care for chemotherapy sensitive disease.
Ciguatoxicity of Gambierdiscus and Fukuyoa species from the Caribbean and Gulf of Mexico

Dinoflagellate species belonging to the genera Gambierdiscus and Fukuyoa produce ciguatoxins (CTXs), potent neurotoxins that concentrate in fish causing ciguatera fish poisoning (CFP) in humans. While the structures and toxicities of ciguatoxins isolated from fish in the Pacific and Caribbean are known, there are few data on the variation in toxicity between and among species of Gambierdiscus and Fukuyoa. Quantifying the differences in species-specific toxicity is especially important to developing an effective cell-based risk assessment strategy for CFP. This study analyzed the ciguatoxicity of 33 strains representing seven Gambierdiscus and one Fukuyoa species using a cell based Neuro-2a cytotoxicity assay. All strains were isolated from either the Caribbean or Gulf of Mexico. The average toxicity of each species was inversely proportional to growth rate, suggesting an evolutionary trade-off between an investment in growth versus the production of defensive compounds. While there is 2- to 27-fold variation in toxicity within species, there was a 1740-fold difference between the least and most toxic species. Consequently, production of CTX or CTX-like compounds is more dependent on the species present than on the random occurrence of high or low toxicity strains. Seven of the eight species tested (G. belizeanus, G. caribaeus, G. carolinianus, G. carpenteri, Gambierdiscus ribotype 2, G. silvae and F. ruetzleri) exhibited low toxicities, ranging from 0 to 24.5 fg CTX3C equivalents cell-1, relative to G. excentricus, which had a toxicity of 469 fg CTX3C eq. cell-1. Isolates of G. excentricus from other regions have shown similarly high toxicities. If the hypothesis that G. excentricus is the primary source of ciguatoxins in the Atlantic is confirmed, it should be possible to identify areas where CFP risk is greatest by monitoring only G. excentricus abundance using species-specific molecular assays.
Psychological well-being status among medical and dental students in Makkah, Saudi Arabia: A cross-sectional study

Abstract Objectives: Medical and dental students experience poor psychological well-being relative to their peers. This study aimed to assess the psychological well-being among medical and dental students in Saudi Arabia, identify the high-risk groups and assess the association between the psychological well-being and the academic performance. Methods: In this cross-sectional study, 422 preclinical medical and dental students at Umm Al-Qura University, Saudi Arabia, were recruited to assess their depression, anxiety, stress, self-efficacy and satisfaction with life levels using 21-items Depression Anxiety Stress Scale (DASS-21), General Self-Efficacy (GSE) scale and Satisfaction With Life Scale (SWLS). Students’ academic weighted grades were obtained later. Descriptive statistics and univariate general linear model were used to analyse data. Results: High levels of depression (69.9%), anxiety (66.4%) and stress (70.9%) were indicated, whereas self-efficacy (mean = 27.22, sd = 4.85) and life satisfaction (mean = 23.60, sd = 6.37) were within the normal range. Female medical students had higher psychological distress in contrast to dental students. In general, third-year students were more depressed and stressed in comparison with second-year students, except for stress among dental students. Moreover, all females had higher self-efficacy than males. Life satisfaction was higher within the second-year and high family income students. Depression was the only psychological variable correlated with the academic performance. Conclusion: High levels of psychological distress were found. Female medical students had higher psychological distress than males, whereas male dental students had higher distress than female. Medical students at third year were more depressed and stressed. Dental students were more depressed in the third year, but more stressed in the second year. Attention should be directed towards reducing the alarming levels of depression, anxiety and stress among medical and dental students.
Predictors of Peritonitis and the Impact of Peritonitis on Clinical Outcomes of Continuous Ambulatory Peritoneal Dialysis Patients in Taiwan—10 Years’ Experience in a Single Center

♦ Objective: Peritoneal dialysis (PD) has become more prevalent as a treatment modality for end-stage renal disease, and peritonitis remains one of its most devastating complications. The aim of the present investigation was to examine the frequency and predictors of peritonitis and the impact of peritonitis on clinical outcomes. ♦ Methods: Our retrospective observational cohort study enrolled 391 patients who had been treated with continuous ambulatory PD (CAPD) for at least 90 days. Relevant demographic, biochemical, and clinical data were collected for an analysis of CAPD-associated peritonitis, technique failure, drop-out from PD, and patient mortality. ♦ Results: The peritonitis rate was 0.196 episodes per patient-year. Older age (>65 years) was the only identified risk factor associated with peritonitis. A multivariate Cox regression model demonstrated that technique failure occurred more often in patients experiencing peritonitis than in those free of peritonitis (p < 0.001). Kaplan-Meier analysis revealed that the group experiencing peritonitis tended to survive longer than the group that was peritonitis-free (p = 0.11). After multivariate adjustment, the survival advantage reached significance (hazard ratio: 0.64; 95% confidence interval: 0.46 to 0.89; p = 0.006). Compared with the peritonitis-free group, the group experiencing peritonitis also had more drop-out from PD (p = 0.03). ♦ Conclusions: The peritonitis rate was relatively low in the present investigation. Elderly patients were at higher risk of peritonitis episodes. Peritonitis independently predicted technique failure, in agreement with other reports. However, contrary to previous studies, all-cause mortality was better in patients experiencing peritonitis than in those free of peritonitis. The underlying mechanisms of this presumptive “peritonitis paradox” remain to be clarified.
A Box-Counting Method with Adaptable Box Height for Measuring the Fractal Feature of Images

Most of the existing box-counting methods for measuring fractal features are only applicable to square images or images with each dimension equal to the power of 2 and require that the box at the top of the box stack of each image block is of the same height as that of other boxes in the same stack, which gives rise to inaccurate estimation of fractal dimension. In this paper, we propose a more accurate box-counting method for images of arbitrary size, which allows the height of the box at the top of each grid block to be adaptable to the maximum and minimum gray-scales of that block so as to circumvent the common limitations of existing box-counting methods.
Human dendritic cells. Enrichment and characterization from peripheral blood

Previous studies demonstrated that lymphoid tissues of mice and rats contain small numbers (less than 1 percent of nucleated cells) of dendritic cells (DC) with special cytologic, surface, and functional properties. We show here that similar DC represent 0.1-0.5 percent of human peripheral blood mononuclear cells. DC can be enriched to 20-60 percent purity by a multistep procedure analogous to that used in mice. Adherent peripheral blood mononuclear cells are cultured overnight, and the released cells are depleted of monocytes and B cells by readherence to plastic, rosetting with erythrocytes coated with anti-human IgG, and centrifugation in dense albumin columns. Enriched DC have similar cytologic features to rodent DC by light and electron microscopy. DC express HLA, and HLA-DR and the leukocyte-common antigens. They lack phagocytic capacity, receptors for antibody-coated and neuraminidase-treated erythrocytes, surface and intracellular Ig, esterase, peroxidase, and azurophilic granules. DC do not react with several monoclonal antibodies directed to phagocytes (OKM 1, “mac-1,” 63D3, and 61D3) and T cells (OKT 3, 6, 8). Unlike the mouse, human DC express complement receptors. When maintained in culture for 4 d, human DC did not give rise to either B cells or monocytes. Therefore, DC identified by cytologic criteria are distinct from other leukocytes. Enriched populations of DC have been compared to fractions enriched in monocytes, B cells, and T cells in three functional assays: stimulation of the primary allogeneic mixed leukocyte reaction, stimulation of the primary syngeneic MLR, and accessory function for the proliferation of periodate- modified T cells. In each case, the DC fraction was 10-fold or more active than other cell fractions. We conclude that DC circulate in man, and represent the principal cell type required for the initiation of several immune responses.
FastInf: An Efficient Approximate Inference Library

The FastInf C++ library is designed to perform memory and time efficient approximate inference in large-scale discrete undirected graphical models. The focus of the library is propagation based approximate inference methods, ranging from the basic loopy belief propagation algorithm to propagation based on convex free energies. Various message scheduling schemes that improve on the standard synchronous or asynchronous approaches are included. Also implemented are a clique tree based exact inference, Gibbs sampling, and the mean field algorithm. In addition to inference, FastInf provides parameter estimation capabilities as well as representation and learning of shared parameters. It offers a rich interface that facilitates extension of the basic classes to other inference and learning methods.
A Melting Pot of Old World Begomoviruses and Their Satellites Infecting a Collection of Gossypium Species in Pakistan

CLCuD in southern Asia is caused by a complex of multiple begomoviruses (whitefly transmitted, single-stranded [ss]DNA viruses) in association with a specific ssDNA satellite; Cotton leaf curl Multan betasatellite (CLCuMuB). A further single ssDNA molecule, for which the collective name alphasatellites has been proposed, is also frequently associated with begomovirus-betasatellite complexes. Multan is in the center of the cotton growing area of Pakistan and has seen some of the worst problems caused by CLCuD. An exhaustive analysis of the diversity of begomoviruses and their satellites occurring in 15 Gossypium species (including G. hirsutum, the mainstay of Pakistan's cotton production) that are maintained in an orchard in the vicinity of Multan has been conducted using φ29 DNA polymerase-mediated rolling-circle amplification, cloning and sequence analysis. The non-cultivated Gossypium species, including non-symptomatic plants, were found to harbor a much greater diversity of begomoviruses and satellites than found in the cultivated G. hirsutum. Furthermore an African cassava mosaic virus (a virus previously only identified in Africa) DNA-A component and a Jatropha curcas mosaic virus (a virus occurring only in southern India) DNA-B component were identified. Consistent with earlier studies of cotton in southern Asia, only a single species of betasatellite, CLCuMuB, was identified. The diversity of alphasatellites was much greater, with many previously unknown species, in the non-cultivated cotton species than in G. hirsutum. Inoculation of newly identified components showed them to be competent for symptomatic infection of Nicotiana benthamiana plants. The significance of the findings with respect to our understanding of the role of host selection in virus diversity in crops and the geographical spread of viruses by human activity are discussed.
Systems Biology-Based Identification of Crosstalk between E2F Transcription Factors and the Fanconi Anemia Pathway

Fanconi anemia (FA) is an autosomal recessive disorder characterized by congenital abnormalities, bone marrow failure, chromosome fragility, and cancer susceptibility. At least eleven members of the FA gene family have been identified using complementation experiments. Ubiquitin-proteasome has been shown to be a key regulator of FA proteins and their involvement in the repair of DNA damage. Here, we identified a novel functional link between the FA/BRCA pathway and E2F-mediated cell cycle regulome. In silico mining of a transcriptome database and promoter analyses revealed that a significant number of FA gene members were regulated by E2F transcription factors, known to be pivotal regulators of cell cycle progression – as previously described for BRCA1. Our findings suggest that E2Fs partly determine cell fate through the FA/BRCA pathway.
"Bring your own laptop unless you want to follow the lecture": alternative communication in the classroom

The introduction of laptops and wireless networks in classrooms has increased the possibilities for student-teacher interaction. Here we explore the premises for this interaction by studying the use of ActiveClass, a system that enables students to ask questions electronically and anonymously in-class. The study emphasizes how the diverse prerequisites for teaching interaction separates students even more in the classroom. We then suggest a differentiated approach to the introduction of interactive technologies in the class room.
Emotional experience, facial expression, and startle reflex modulation in young adults, healthy older adults, and Alzheimer's disease

This study was designed to assess the impact of aging and Alzheimer's disease on conscious appraisal of emotional experience, facial expression, and emotion-modulated action tendencies. Participants included healthy young adults (YA), healthy older adults (OA), and individuals in the early stages of Alzheimer's disease (AD). Self-report of emotional experience while viewing emotionally-salient images was recorded, action tendencies in the form of eye-blink startle reflex modulation and its resolution over time (300ms and 3000ms post-stimulus offset) were recorded, and facial expression of emotion was assessed utilizing EMG recordings of corrugator and zygomatic facial muscles. Consistent with previous studies of emotion in YA, showed the predicted linear relationship with normatively-determined image type (positive, neutral, & negative), and arousal experience ratings were in the predicted quadratic pattern. Corrugator EMG activity increased while viewing negative images and zygomatic EMG activity increased while viewing positive images, as predicted. Startle reflex magnitude was observed in the predicted valenced direction (i.e., greatest for negative images) while viewing images and 300ms post-image removal, but this pattern inverted at the 3000ms probe-time. Similar findings were observed in a comparison of the YA and OA groups, however a difference was observed in the resolution of the startle reflex, with the expected valenced pattern dissipating by the 300ms probe-time for the OA group. Comparisons of the OA and AD groups were limited by small sample sizes, but the AD group was similar to the OA group on measures of self-report of emotional experience patterns and corrugator EMG activity. Zygomatic EMG activity while viewing positive images appeared reduced
Concise Review: Workshop Review: Understanding and Assessing the Risks of Stem Cell‐Based Therapies

The field of stem cell therapeutics is moving ever closer to widespread application in the clinic. However, despite the undoubted potential held by these therapies, the balance between risk and benefit remains difficult to predict. As in any new field, a lack of previous application in man and gaps in the underlying science mean that regulators and investigators continue to look for a balance between minimizing potential risk and ensuring therapies are not needlessly kept from patients. Here, we attempt to identify the important safety issues, assessing the current advances in scientific knowledge and how they may translate to clinical therapeutic strategies in the identification and management of these risks. We also investigate the tools and techniques currently available to researchers during preclinical and clinical development of stem cell products, their utility and limitations, and how these tools may be strategically used in the development of these therapies. We conclude that ensuring safety through cutting‐edge science and robust assays, coupled with regular and open discussions between regulators and academic/industrial investigators, is likely to prove the most fruitful route to ensuring the safest possible development of new products.
Microstructured Optical Fiber for Residual Dispersion Compensation Over $S + C + L + U$ Wavelength Bands

A defected-core microstructured optical fiber (MOF) is numerically investigated for the purpose of residual chromatic dispersion compensation from telecom link. The designed MOF exhibits ultraflattened negative dispersion over S + C + L + U wavelength bands and average dispersion of about -179 ps/nm/km with an absolute dispersion variation of 2.1 ps/nm/km from 1.480 to 1.675 mum (195-nm bandwidth). The designed fiber has eight rings of holes in the cladding resulting in low confinement loss of ~0.002 dB/km at 1.55 mum, and small effective mode area ~6 mum2. To evaluate the feasibility of such proposed MOF, a dimensional sensitivity analysis and an evaluation of coupling efficiency between the designed fiber and a conventional single-mode fiber have been carried out.
The pharmacological characterization of a novel selective 5-hydroxytryptamine1A receptor antagonist, NAD-299.

The pharmacological properties of a novel selective 5-hydroxytryptamine1A (5-HT1A) receptor antagonist, NAD-299 [(R)-3-N,N-dicyclobutylamino-8-fluoro-3,4-dihydro-2H-1-benzopyran-5-carboxamide hydrogen (2R,3R)-tartrate monohydrate] were examined in vitro and in vivo and compared with the reference 5-HT1A receptor antagonist, WAY-100635 [N-(2-(1-(4-(2-methoxyphenyl)piperazin-yl))ethyl)-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride]. The new compound had high affinity for 5-HT1A receptors in vitro with a Ki value of 0.6 nM. The only other receptors for which NAD-299 had affinity less than 1 microM were alpha-1 and beta adrenoceptors with Ki values of 260 and 340 nM, respectively. Thus, the selectivity of NAD-299 for 5-HT1A receptors was more than 400 times. WAY-100635 had considerably higher affinity than NAD-299 for alpha-1 adrenoceptors (Ki = 45 nM) and dopamine D2 and D3 receptors (Ki = 79 and 67 nM, respectively). Like WAY-100635, NAD-299 competitively blocked 5-HT-induced inhibition of vasoactive intestinal peptide-stimulated cAMP production in GH4ZD10 cells and had no intrinsic activity. Both compounds were therefore 5-HT1A receptor antagonists in vitro and also behaved as such in in vivo experiments. Thus, they competitively antagonized the 8-hydroxy-2-(di-n-propylamino)tetralin-induced 5-HT behavioral effects, hypothermia, corticosterone secretion and inhibition of passive avoidance behavior without causing any actions of their own. The effective dose of NAD-299 varied between 0.03 and 0.35 micromol/kg s.c. , depending on the test and the dose of 8-hydroxy-2-(di-n-propylamino)tetralin.
Modeling language discrimination in infants using i-vector representations

Experimental research suggests that at birth infants can discriminate two languages if they belong to different rhythmic classes, and by 4 months of age they can discriminate two languages within the same class provided they have been previously exposed to at least one of them. In this paper, we present a novel application of speech technology tools to model language discrimination, which may help to understand how infants achieve high performance on this task. By combining a Gaussian Mixture Model of the acoustic space and lowdimensional representations of novel utterances with a model of a habituation paradigm, we show that brief exposure to French does not allow to discriminate between two previously unheard languages with similar phonological properties, but facilitates discrimination of two phonologically distant languages. The implications of these findings are discussed.
Coxiella burnetii exploits host cAMP‐dependent protein kinase signalling to promote macrophage survival

Intracellular bacterial pathogens often subvert apoptosis signalling to regulate survival of their host cell, allowing propagation of the bacterial population. Coxiella burnetii, the intracellular agent of human Q fever, inhibits host cell apoptosis through several mechanisms, including prevention of mitochondrial cytochrome c release, triggering of an anti‐apoptotic transcriptional programme, and activation of pro‐survival kinases. To control host cell survival, C. burnetii delivers effector proteins to the eukaryotic cytosol using a specialized Dot/Icm type IV secretion system (T4SS). Effectors are predicted to regulate activity of pro‐survival host signalling proteins, such as Akt and cAMP‐dependent protein kinase (PKA), to control infection. Here, we show that host PKA activity is required for C. burnetii inhibition of macrophage apoptosis. PKA is activated during infection and inhibits activity of the pro‐apoptotic protein Bad via phosphorylation. Bad is also phosphorylated at an Akt‐specific residue, indicating C. burnetii uses two kinases to fully inactivate Bad. Additionally, Bad and the tethering protein 14‐3‐3β colocalize at the C. burnetii parasitophorous vacuole (PV) membrane during infection, an event predicted to alter Bad promotion of apoptosis. Inhibiting PKA activity prevents Bad recruitment to the PV, but the protein is retained at the membrane during induction of apoptosis. Finally, PKA regulatory subunit I (RI) traffics to the PV membrane in a T4SS‐dependent manner, suggesting a C. burnetii effector(s) regulates PKA‐dependent activities. This study is the first to demonstrate subversion of host PKA activity by an intracellular bacterial pathogen to prevent apoptosis and survive within macrophages.