Miracle-dz/UniFAR-FTUs huggingface dataset:
Plasmablastic Transformation of Low-grade B-cell Lymphomas: Report on 6 Cases

Histologic transformation of low-grade B-cell lymphoma to diffuse large B-cell lymphoma is associated with poor prognosis. Although plasma cell differentiation is common in these lymphomas, an overt plasmablastic transformation (PBL-T) has been only rarely reported. We report 6 cases of PBL-T occurring in 3 chronic lymphocytic leukemias (CLL) and 3 follicular lymphomas. Five patients were men, and the mean age was 65 years (range, 52 to 72 y). None of them had history of immunodeficiency. In 3 cases the PBL-T occurred 34 to 85 months after the initial diagnosis, and in 3 it was detected simultaneously with the small cell component at diagnosis. All patients received chemotherapy after transformation, and 4 died 4 to 24 months after this diagnosis. In 3 cases, PBL-T occurred in an extranodal site. All PBL-Ts had immunoblastic morphology with admixed plasma cells, were CD20 and PAX5 negative, expressed &lgr; light chain, and 5 were CD138 positive. All cases were negative for HHV8, and only 1 PBL-T was Epstein-Barr virus positive. Evidence of a clonal relationship between the small cell and PBL-T components was found in 5 cases. In 2 CLL cases, both components had 13q deletions, and in all follicular lymphoma cases both components harbored the t(14;18) translocation. MYC translocations were observed in 2 cases transformed from a CLL. In conclusion, PBL-T expands the clinicopathologic spectrum of the transformation of low-grade B-cell lymphomas. These transformed tumors are clinically, histologically, and phenotypically similar to primary plasmablastic lymphomas, but they are not associated with immunodeficiency and rarely have Epstein-Barr virus infection or MYC alterations.
Association of genetic variants in the neurotrophic receptor-encoding gene NTRK2 and a lifetime history of suicide attempts in depressed patients.

CONTEXT A consistent body of evidence supports a role of reduced neurotrophic signaling in the pathophysiology of major depressive disorder (MDD) and suicidal behavior. Especially in suicide victims, lower postmortem brain messenger RNA and protein levels of neurotrophins and their receptors have been reported. OBJECTIVE To determine whether the brain-derived neurotrophic factor (BDNF) gene or its high-affinity receptor gene, receptor tyrosine kinase 2 (NTRK2), confer risk for suicide attempt (SA) and MDD by investigating common genetic variants in these loci. DESIGN Eighty-three tagging single-nucleotide polymorphisms (SNPs) covering the genetic variability of these loci in European populations were assessed in a case-control association design. SETTING Inpatients and screened control subjects. PARTICIPANTS The discovery sample consisted of 394 depressed patients, of whom 113 had SA, and 366 matched healthy control subjects. The replication studies comprised 744 German patients with MDD and 921 African American nonpsychiatric clinic patients, of whom 152 and 119 were positive for SA, respectively. INTERVENTIONS Blood or saliva samples were collected from each participant for DNA extraction and genotyping. MAIN OUTCOME MEASURES Associations of SNPs in BDNF and NTRK2 with SA and MDD. RESULTS Independent SNPs within NTRK2 were associated with SA among depressed patients of the discovery sample that could be confirmed in both the German and African American replication samples. Multilocus interaction analysis revealed that single SNP associations within this locus contribute to the risk of SA in a multiplicative and interactive fashion (P = 4.7 x 10(-7) for a 3-SNP model in the combined German sample). The effect size was 4.5 (95% confidence interval, 2.1-9.8) when patients carrying risk genotypes in all 3 markers were compared with those without any of the 3 risk genotypes. CONCLUSIONS Our results suggest that a combination of several independent risk alleles within the NTRK2 locus is associated with SA in depressed patients, further supporting a role of neurotrophins in the pathophysiology of suicide.
Plasma elimination kinetics for factor VII are independent of its activation to factor VIIa and complex formation with plasma inhibitors

Summary The mechanism for the elimination of factor VII (FVII) from the circulation is unknown, just as it is unclear how activation of FVII to FVIIa and subsequent complex formation with antithrombin III (AT) or α2-macroglobulin (α2M) affects clearance. The possibility that the clearance mechanism involves activation and inhibitor complex formation as obligatory intermediate reactions is examined in this study. Human and murine sera were spiked with human FVIIa in the absence and presence of heparin and analysed for complex formation. Complex formation in vivo was studied after intravenous injection of 125I-VIIa in mice; and the pharmacokinetics (PK) of human and murine FVIIa was studied in normal mice. Furthermore, comparative PK studies were performed with FVII, FVIIa, active site blocked FVIIa and a preformed FVIIa-AT complex in normal and α2M-deficient mice. The data demonstrated that FVIIa-AT complexes and to a much lesser extent FVIIa-α2M-complexes accumulated in vivo after FVIIa administration. FVIIa-AT accounted for about 50% of total FVIIa antigen left in the circulation after 3 hours. All FVII derivatives studied including FVII, FVIIa and FVIIa-AT were cleared with similar rates suggesting an elimination kinetics which is unaffected by FVII activation and subsequent inactivation by plasma inhibitors.
Long-term dynamical evolution of pallene (Saturn XXXIII) and its diffuse, dusty ring

The distinctive set of Saturnian small satellites, Aegaeon, Methone, Anthe, and Pallene, constitutes an excellent laboratory to understand the evolution of systems immersed in co-orbital dusty rings/arcs, subjected to perturbations from larger satellites and non-gravitational forces. In this work, we carried out a comprehensive numerical exploration of the long-term evolution of Pallene and its ring. Through frequency map analysis, we characterised the current dynamical state around Pallene. A simple tidal evolution model serves to set a time frame for the current orbital configuration of the system. With detailed short and long-term N-body simulations we determine whether Pallene is currently in resonance with one or more of six of Saturn’s major moons. We analysed a myriad of resonant arguments extracted from the direct and indirect parts of the disturbing function, finding that Pallene is not in mean motion resonance from the present up to 5 Myr into the future; none the less, some resonant arguments exhibit intervals of libration and circulation at different timescales and moon pairings. We studied the dynamical evolution of micrometric particles forming the ring, considering gravitational and non-gravitational forces. Non-gravitational forces are responsible for particles vertical excursions and outward migration. By estimating the satellite’s mass production rate, we find that Pallene could be responsible for keeping its ring in steady-state only if it is mainly composed of large micrometre-sized particles. If mainly composed of particles with a few micrometres for which Pallene is the only source, the ring will spread out, both radially and vertically, until it finally disappears.
Fast Sensing and Quenching of CMOS SPADs for Minimal Afterpulsing Effects

We present a single-photon avalanche diode (SPAD) front-end circuitry, in a cost-effective 0.35 μm CMOS technology, for single-photon detection in the visible wavelength range, aimed at speeding up the sensing of detector ignition and at promptly quenching the avalanche current buildup. The circuit allows the reduction in detrimental effects of afterpulsing through reducing any delays in the electronics intervention on the detector and through a proper time-varying action of the MOS transistors on the different SPAD's operating conditions. The sensing time is reduced down to a few hundreds of picoseconds, with an active quenching transition of about 1 ns for 6 V excess bias, and a final reset in just 3 ns.
Impaired aerobic work capacity in insulin dependent diabetics with increased urinary albumin excretion

To assess whether decreased aerobic work capacity was associated with albuminuria in insulin dependent diabetics aerobic capacity was measured in three groups of 10 patients matched for age, sex, duration of diabetes, and degree of physical activity. Group 1 comprised 10 patients with normal urinary albumin excretion (<30 mg/24 h), group 2 comprised 10 with incipient diabetic nephropathy (urinary albumin excretion 30-300 mg/24 h, and group 3 comprised 10 with clinical diabetic nephropathy (urinary albumin excretion >300 mg/24 h). Ten non-diabetic subjects matched for sex, age, and physical activity served as controls. Oxygen uptake was similar in the four groups at rest and during a 75 W workload. Maximal oxygen uptake was also similar in the control subjects and group 1 (median 41·7, (range 29·1-53·0) ml/kg/min v 38·5 (26·6-59·2) ml/kg/min, respectively), but was significantly lower in group 2 (27·7 (13·9-44·3) ml/kg/min) and group 3 (26·8 (22·6-36·7) ml/kg/min). The difference in maximal oxygen uptake between groups 1 and 2 was 10·8 ml/kg/min (95% confidence interval 3·6 to 23·4 ml/kg/min) and between groups 1 and 3, 11·7 ml/kg/min (4·9 to 22·5 ml/kg/min). These differences were not explained by differences in metabolic control or the degree of autonomic neuropathy. Thus the insulin dependent diabetics with only slightly increased urinary albumin excretion had an appreciably impaired aerobic work capacity which could not be explained by autonomic neuropathy or the duration of diabetes. Whether the reduced capacity is due to widespread microangiopathy or another pathological process affecting the myocardium remains to be established.
One‐Lung Anesthesia: Percent Shunt and Arterial Oxygen Tension during Continuous Insufflation of Oxygen to the Nonventilated Lung

Twenty-four male patients scheduled for elective pulmonary resection were studied to determine whether continuous insufflation of oxygen to the nonventilated lung would reduce intrapulmonary shunting (&OV0244;s/&OV0244;t) and arterial oxygen desaturation. Measurements of physiologic variables were made using pulmonary arterial and peripheral arterial catheters. Blood was sampled for analysis and &OV0244;s/&OV0244;t and other hemodynamic variables were calculated. Significant differences were observed in &OV0244;s/&OV0244;t and arterial oxygen tensions (PaO2) between patients in whom oxygen was insufflated and those in whom oxygen was not insufflated. Patients with oxygen insufflation had significantly lower &OV0244;s/&OV0244;t and consistently higher PaO2. Statistically significant differences in &OV0244;s/&OV0244;t became apparent after 15, 30, and 45 minutes of one-lung ventilation compared with values for patients not receiving oxygen insufflation. Six of 12 patients without oxygen insufflation had peak &OV0244;s/&OV0244;t levels greater than 50%, whereas none of the patients in whom oxygen was insufflated had levels that exceeded this amount. Of 12 patients given oxygen insufflation, one had a PaO2 of less than 100 torr at the point of maximum decrease in arterial oxygen tension, compared with six of 12 patients in whom oxygen was not insufflated. These findings suggest that continuous oxygen insufflation of the nonventilated lung during periods of one-lung ventilation reduces &OV0244;s/&OV0244;t and minimizes arterial oxygen desaturation.
Induction of transforming growth factor‐beta and prostaglandin E2 production by ethanol in human monocytes

To test our hypothesis that monocytes (MØ) and their mediators are major contributors to ethanol‐ related immunodepression, the modulating capacity of acute ethanol treatment was assessed on the production of transforming growth factor‐beta (TGFβ) and prostaglandin E2 (PGE2) by human peripheral blood MØ. We demonstrate that acute in vitro treatment of adherent MO with either 50 or 150 mM ethanol induced a significant increase in the production of TGFβ (P < 0.045 and β < 0.001, respectively). Furthermore, MØ pretreatment with both 50 and 150 mM ethanol augmented TGFjS production in response to subsequent stimulation with the synthetic bacterial analog, muramyl dipeptide (MDP) (P < 0.05 and β < 0.001, respectively). Ethanol also increased TGFØ production in interferon β (IFNβ)‐ activated MØ in response to MDP stimulus (P < 0.05). MØ TGFβ levels, however, were always lower in IFNβ‐ activated than in non‐IFNβ‐activated MØ after the same stimulation with ethanol plus MDP, suggesting that MØ preactivation by IFN7 can partially counteract the TGFβ inducing potential of ethanol. Similar to its TGFβ ‐ inducing potential, ethanol (150 mM) had the capacity to induce PGE2 production in adherent human MØ (P < 0.045). However, ethanol failed to augment MØ PGE2 production induced by the PGE2 secretagogue, MDP. TGFjS induction by ethanol was unaffected by the presence of cyclooxygenase inhibitor, suggesting that ethanol‐induced MØ TGFß production does not require MØ PG£2 production. These results indicate that ethanol is a potent inducer for inhibitory MØ mediators, TGFjS and PGE2, and also has the capacity to augment MØ TGFß production in response to subsequent stimulation. Thus, ethanol‐induced elevation of MØ TGFß and PGE2 production might contribute to decreased β cell proliferation and abnormal MØ functions after alcohol exposure, resulting in a depressed immune response.
Vesicle-associated Membrane Protein (VAMP) Cleavage by a New Metalloprotease from the Brazilian Scorpion Tityus serrulatus*

We present evidence that venom from the Brazilian scorpion Tityus serrulatus and a purified fraction selectively cleave essential SNARE proteins within exocrine pancreatic tissue. Western blotting for vesicle-associated membrane protein type v-SNARE proteins (or synaptobrevins) reveals characteristic alterations to venom-treated excised pancreatic lobules in vitro. Immunocytochemistry by electron microscopy confirms both the SNARE identity as VAMP2 and the proteolysis of VAMP2 as a marked decrease in secondary antibody-conjugated colloidal gold particles that are predominantly associated with mature zymogen granules. Studies with recombinant SNARE proteins were used to determine the specific cleavage site in VAMP2 and the susceptibility of VAMP8 (endobrevin). The VAMP2 cleavage site is between the transmembrane anchor and the SNARE motif that assembles into the ternary SNARE complex. Inclusion of divalent chelating agents (EDTA) with fraction ν, an otherwise active purified component from venom, eliminates SNARE proteolysis, suggesting the active protein is a metalloprotease. The unique cleavages of VAMP2 and VAMP8 may be linked to pancreatitis that develops following scorpion envenomation as both of these v-SNARE proteins are associated with zymogen granule membranes in pancreatic acinar cells. We have isolated antarease, a metalloprotease from fraction ν that cleaves VAMP2, and report its amino acid sequence.
Patterns and correlates of cannabis use among individuals with HIV/AIDS in Maritime Canada.

BACKGROUND The prevalence of cannabis use in HIV-infected individuals is high and its long-term effects are unclear. METHODS The prevalence, perceived benefits and consequences, and predictors of cannabis use were studied using a cross-sectional survey in two immunodeficiency clinics in Maritime Canada. RESULTS Current cannabis use was identified in 38.5% (87 of 226) of participants. Almost all cannabis users (85 of 87 [97.7%]) acknowledged its use for recreational purposes, with 21.8% (19 of 87) reporting medicinal cannabis use. The majority of patients enrolled in the present study reported mild or no symptoms related to HIV (n=179). Overall, 80.5% (70 of 87) of the cannabis-using participants reported a symptom-relieving benefit, mostly for relief of stress, anorexia or pain. Participants consumed a mean (± SD) of 18.3±21.1 g of cannabis per month and spent an average of $105.15±109.87 on cannabis per month. Cannabis use was associated with rural residence, lower income level, driving under the influence of a substance, and consumption of ecstasy and tobacco. Income level, ecstasy use and tobacco use were retained as significant predictors in regression modelling. Cannabis use was not associated with adverse psychological outcomes. DISCUSSION Prolonged previous cannabis consumption and the substantial overlap between recreational and medicinal cannabis use highlight the challenges in obtaining a tenable definition of medicinal cannabis therapy.
Adaptive response in mouse bone-marrow stromal cells exposed to 900-MHz radiofrequency fields: Gamma-radiation-induced DNA strand breaks and repair

ABSTRACT The aim of this study was to examine whether radiofrequency field (RF) preexposure induced adaptive responses (AR) in mouse bone-marrow stromal cells (BMSC) and the mechanisms underlying the observed findings. Cells were preexposed to 900-MHz radiofrequency fields (RF) at 120 μW/cm2 power intensity for 4 h/d for 5 d. Some cells were subjected to 1.5 Gy γ-radiation (GR) 4 h following the last RF exposure. The intensity of strand breaks in the DNA was assessed immediately at 4 h. Subsequently, some BMSC were examined at 30, 60, 90, or 120 min utilizing the alkaline comet assay and γ-H2AX foci technique. Data showed no significant differences in number and intensity of strand breaks in DNA between RF-exposed and control cells. A significant increase in number and intensity of DNA strand breaks was noted in cells exposed to GR exposure alone. RF followed by GR exposure significantly decreased number of strand breaks and resulted in faster kinetics of repair of DNA strand breaks compared to GR alone. Thus, data suggest that RF preexposure protected cells from damage induced by GR. Evidence indicates that in RF-mediated AR more rapid repair kinetics occurs under conditions of GR-induced damage, which may be attributed to diminished DNA strand breakage.
Food security: is New Zealand a land of plenty?

AIM To explore the concept of food security (when there is enough, appropriate and acceptable food available) in the adult New Zealand population using the National Nutrition Survey (NNS97). METHODS The stepwise development of indicators of food security included a literature search and focus groups with low income women and men. Key issues surrounding the procurement and provision of food were determined and eight indicator statements prepared for inclusion in NNS97, to be addressed by each participant on behalf of their household. RESULTS Prevalence was significantly higher (p<0.05) for females compared to males for the majority of indicator statements among New Zealand European & Others and Maori. New Zealand European & Others reported the most food security; Pacific people reported the least and Maori fell between the two. There was a significant increasing linear trend of food security with age (p<0.001), after adjusting for gender. "Food runs out in my/our household due to lack of money" was cited more often by female compared to male New Zealand European & Others in NZDep96 quartiles III and IV. CONCLUSION The issue of 'not having enough food' may be more prevalent in New Zealand than US or Australia. Among New Zealand European & Others the higher prevalence of insufficient food due to lack of money among females from NZDep96 quartiles III and IV suggests that males may be protected from this by their female partners. Food security needs to be improved among young adults, women, Maori and Pacific people in order to prevent longer term nutritional health consequences.
Local Therapy in Metastatic Breast Cancer Is Associated With Improved Survival

Patients presenting with stage-IV breast cancer are usually offered systemic chemotherapy to control metastatic tumor burden and palliative radiation therapy to manage the symptomatic primary tumor. The aim of this study was to assess the result of local therapy on the overall outcome of patients with metastatic breast cancer. We reviewed medical records of all patients with metastatic breast cancer that presented to our institution between 2000 and 2009. Based on the treatment received, the patients were grouped as follows: group 1 included patients who underwent surgery and also received radiotherapy and chemotherapy/hormonal therapy, group 2 included patients who received radiotherapy and chemotherapy/hormonal therapy only, and group 3 included patients who received chemotherapy/hormonal therapy alone. Of the 37 patients included in the study, 10 patients were placed in group 1, 17 patients in group 2, and 10 patients in group 3. About 38% had high to anaplastic tumor grade, and 48% had ≥2 metastatic sites in the body. Overall, the average survival time was 3.13 years (range: 0–17 years). A significant difference in survival estimates was noted between groups 1, 2, and 3 with mean survival times of 8.83, 4.9, and 2.26 years, respectively (log rank &khgr;2 = 10.44, P = 0.005). In age-adjusted multivariate Cox regression model (&khgr;2 = 21.729, P= 0.001), high/anaplastic tumor grade (P = 0.036), African American race (P = 0.009), central nervous system metastasis (P = 0.003), group 2 (P = 0.006), and group 3 (P = 0.002) were associated with poor survival. Survival was not associated with estrogen and progesterone receptor and visceral or bone metastases. We conclude that aggressive local control of primary tumor in patients presenting with stage-IV breast cancer is associated with improved survival.
The kidney and hypertension: novel insights from transgenic models

Purpose of reviewDespite decades of study, the pathogenesis of essential hypertension remains obscure, but the kidney appears to play a central role. Technology for manipulation of the mouse genome has been immensely valuable in dissecting pathways involved in blood pressure control. This review summarizes recent studies employing this technology to understand signaling pathways and specific cell lineages within the kidney that are involved in the regulation of sodium excretion impacting blood pressure homeostasis. Recent findingsWe review a series of recent studies of regulatory pathways affecting sodium excretion by the kidney including the renin–angiotensin system, the mineralocorticoid receptor, the endothelin system, nitric oxide, and the with-no-lysine (K)/sterile 20-like kinase pathway. We have specifically highlighted studies utilizing transgenic mouse models, which provide a powerful mechanism for defining the role of proteins and pathways on sodium balance and blood pressure in the intact organism. SummaryThese studies underscore the importance of the kidney in regulation of blood pressure and the pathogenesis of hypertension. Transgenic mouse models provide a powerful approach to identifying key cell lineages and molecular pathways causing hypertension. These pathways represent potential targets for novel antihypertensive therapies.
Reclassification of Desulfotomaculum auripigmentum as Desulfosporosinus auripigmenti corrig., comb. nov.

The species Desulfotomaculum auripigmentum is reclassified as Desulfosporosinus auripigmenti corrig. , comb. nov. on the basis of morphological and physiological traits, phylogenetic position and chemotaxonomic properties. Characteristics supplementary to those provided in the original description reveal that the type strain, DSM 13351(T) (=ATCC 700205(T)), forms oval, subterminal to terminal spores, possesses LL-diaminopimelic acid and contains MK-7 as the predominant menaquinone, while the whole-cell methanolysate contains even-carbon, straight-chain saturated and mono-unsaturated fatty acids and 1,1-dimethylacetals as major components. DNA-DNA reassociation values below 30 % for Desulfosporosinus orientis DSM 765(T) and Desulfosporosinus meridiei DSM 13257(T) demonstrate that strain DSM 13351(T) shows sufficient genomic differences to maintain its species status. Lack of motility, a smaller cell diameter and the ability to use malate and glycerol as electron donors and fumarate and arsenate as electron acceptors are the main properties that differentiate Desulfosporosinus auripigmenti from the other two species of the genus.