Miracle-dz/UniFAR-FTUs huggingface dataset:
New malignancies after blood or marrow stem-cell transplantation in children and adults: incidence and risk factors.

PURPOSE To determine the incidence and risk factors for the development of new malignancies occurring after stem-cell transplantation (SCT). PATIENTS Between January 1, 1974, and March 31, 2001, 3,372 patients underwent SCT at the University of Minnesota. From these transplants, 147 posttransplant malignancies (PTMs) were identified in 137 patients. RESULTS Excluding nonmelanoma skin cancers (n = 19) and carcinoma-in-situ (n = 5), the remaining 123 cases represented an 8.1-fold (95% confidence interval [CI], 6.7 to 9.6) increased risk of a PTM, an excess risk of 102.7 cases/10,000 persons/yr (age and sex adjusted). This includes a significantly elevated risk for developing myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML; standardized incidence ratio [SIR] = 300; 95% CI, 210 to 406), non-Hodgkin's lymphoma including posttransplant lymphoproliferative disorder (PTLD; SIR = 54.3; 95% CI, 39.5 to 41.1), Hodgkin's disease (SIR = 14.8; 95% CI, 3.9 to 32.9), or solid tumors overall (SIR = 2.8; CI, 2.0 to 3.7) and in specific for melanoma, brain, and oral cavity tumors. The cumulative incidence for the development of any PTM was 6.9% (95% CI, 5.2 to 8.6) at 20 years post-SCT. For PTLD (n = 43), the cumulative incidence plateaued at 1.4% (95% CI, 1.0 to 1.8) by 10 years post-SCT. For MDS or AML, the cumulative incidence plateaued at 1.4% (95% CI, 0.9 to 1.9) by 10 years post-SCT. The cumulative incidence of developing a solid tumor did not plateau and was 3.8% (95% CI, 2.2 to 5.4) at 20 years post-SCT. CONCLUSION These data reveal that the risk of PTMs, especially solid tumors, continues to increase even 20 years after transplant, necessitating long-term close follow-up for these patients.
The Efficacy of Trastuzumab in Animal Models of Breast Cancer: A Systematic Review and Meta-Analysis

Background Breast cancer is the most frequent cancers and is the second leading cause of cancer death among women. Trastuzumab is an effective treatment, the first monoclonal antibody directed against the human epidermal growth factor receptor 2 (HER2). To inform the development of other effective treatments we report summary estimates of efficacy of trastuzumab on survival and tumour volume in animal models of breast cancer. Methods We searched PubMed and EMBASE systematically to identify publications testing trastuzumab in animal models of breast cancer. Data describing tumour volume, median survival and animal features were extracted and we assessed quality using a 12-item checklist. We analysed the impact of study design and quality and evidence for publication bias. Results We included data from 83 studies reporting 169 experiments using 2076 mice. Trastuzumab treatment caused a substantial reduction in tumour growth, with tumours in treated animals growing to 32.6% of the volume of tumours in control animals (95%CI 27.8%-38.2%). Median survival was prolonged by a factor of 1.45 (1.30–1.62). Many study design and quality features accounted for between-study heterogeneity and we found evidence suggesting publication bias. Conclusion We have found trastuzumab to be effective in animal breast cancer models across a range of experimental circumstances. However the presence of publication bias and a low prevalence of measures to reduce bias provide a focus for future improvements in preclinical breast cancer research.
The Effect of Biliary Decompression on Bacterial Translocation in Jaundiced Rats

Patients with obstructive jaundice are prone to septic complications after biliary tract operations. Restoring bile flow to the intestine may help to decrease the complication rate. The present study is aimed at evaluating the effect of biliary decompression on bacterial translocation in jaundiced rats. Sixty-six male Sprague-Dawley rats were randomly allocated to six groups subjected to common bile duct ligation (CBDL) and transection (groups 2–6) or sham operation (group 1). In groups and 2 the incidence of enteric bacterial translocation was determined 2 weeks after sham operation or CBDL. In groups 3–6, biliary decompression was achieved by performing a choledochoduodenostomy after 2 weeks of biliary decompression. Bacterial translocation was then studied 1,2,3 and 5 weeks following biliary decompression. The rate of bacterial translocation to mesenteric lymph nodes in obstructive jaundice was significantly higher as compared with controls, and decreased with time to nil three weeks following biliary decompression. The incidence of bacterial translocation was closely correlated (r = 0.844; p = 0.034) with serum alkaline phosphatase activity and seemed to fit with the morphological changes noted in the small intestine. The decrease in bacterial translocation, however, lags behind the recovery of liver function as measured by routine liver function tests and antipyrine clearance. Obstructive jaundice thus promotes bacterial translocation in the rat. Biliary decompression gradually decreases the rate of bacterial translocation.
Schwannoma-derived growth factor promotes the neuronal differentiation and survival of PC12 cells

Schwannoma-derived growth factor (SDGF) was initially isolated from schwannoma cells as a mitogen for glial cells and fibroblasts. The present data show that SDGF causes the morphological and molecular differentiation of rat PC12 cells in a manner similar to, but distinguishable from nerve growth factor (NGF). It also promotes PC12 survival in serum-free conditions. SDGF induced changes include neurite outgrowth and the induction of the mRNAs for GAP-43 and transin, proteins which are highly expressed in axons. In addition, both SDGF and NGF induce the transcription factor, NGFI-A. The time course of the response to SDGF is similar to that for NGF. Gap-43 mRNA induction by both SDGF and NGF is inhibited by dexamethasone, but dexamethasone has no effect on NGFI-A mRNA synthesis. These observations show that SDGF has a differentiation and survival promoting effect on PC12 cells in addition to its mitogenic activity on glial cells and fibroblasts.
Landscape dynamics of aspen and conifer forests

Quaking aspen (Populus tremuloides Michx.) is widely dispersed across the landscape of North America. Seventy-five percent of the aspen in the western United States occurs in the states of Colorado (50%) and Utah (25%). Reproduction in aspen is primarily by asexual means, e.g., root sprouts that are generally referred to as suckers. An aspen clone consists of numerous stems that are genetically alike that began from a single seed that germinated sometime in the past. Generally, these clones have been perpetuated on site by disturbance that allowed the clones to survive and expand in the area. The importance of aspen in the Interior West is well described and documented in the literature. Besides adding diversity to the landscape, aspen also provides water, forage, wood products, and so on for use by the public. Since European settlement, the natural disturbance regime (usually fire) has been interrupted. This has caused much of the aspen-dominated lands to succeed to conifers. The decline in aspen ranges from 49% in Colorado to 95% in Arizona. Numerous techniques are available to aid the manager in restoring aspen to a level approaching its historical occurrence.
The extensibility of the cervix uteri of the rat at different times of pregnancy

The mechanical properties of the cervix uteri, during pregnancy in the rat, show two distinct changes; first, an increase in the circumference of the collagenous framework, and, second, an increase in its extensibility under prolonged loading (Harkness & Harkness, 1959). In this earlier investigation the time course of the change in extensibility was not studied in detail, only that of the change in circumference. In a subsequent investigation on the effect of hormones on the mechanical properties of the cervix it was found that a mixture of oestradiol, progesterone and relaxin could increase the circumference of the cervix to a size corresponding to the 17th-18th day ofpregnancy, but had little effect on its extensibility (Cullen & Harkness, 1960). It therefore became of interest to establish the time course of change of extensibility of the cervix during pregnancy, and to relate it to the change in circumference. In addition, previous work had shown an abrupt change in the physical properties of the foetal membranes about three days before the end of pregnancy (Harkness & Harkness, 1956) and we thought this might be related to similar change in the birth canal. The present investigation has shown that this is not so. The time course of the change in extensibility of the cervix has proved to be similar to that of the circumference, both showing little alteration until the 12th day, after which they increase progressively until the end of pregnancy.
Role of RyR2 Phosphorylation in Heart Failure and Arrhythmias: Protein Kinase A–Mediated Hyperphosphorylation of the Ryanodine Receptor at Serine 2808 Does Not Alter Cardiac Contractility or Cause Heart Failure and Arrhythmias

This Controversies in Research article discusses the hypothesis that protein kinase A (PKA)-mediated phosphorylation of the Ryanodine Receptor (RyR) at a single serine (RyRS2808) is essential for normal sympathetic regulation of cardiac myocyte contractility and is responsible for the disturbed Ca2+ regulation that underlies depressed contractility in heart failure. Studies supporting this hypothesis have associated hyperphosphorylation of RyRS2808 and heart failure progression in animals and humans and have shown that a phosphorylation defective RyR mutant mouse (RyRS2808A) does not respond normally to sympathetic agonists and does not exhibit heart failure symptoms after myocardial infarction. Studies to confirm and extend these ideas have failed to support the original data. Experiments from many different laboratories have convincingly shown that PKA-mediated RyRS2808 phosphorylation does not play any significant role in the normal sympathetic regulation of sarcoplasmic reticulum Ca2+ release or cardiac contractility. Hearts and myocytes from RyRS2808A mice have been shown to respond normally to sympathetic agonists, and to increase Ca2+ influx, Ca2+ transients, and Ca2+ efflux. Although the RyR is involved in heart failure–related Ca2+ disturbances, this results from Ca2+-calmodulin kinase II and reactive oxygen species–mediated regulation rather than by RyR2808 phosphorylation. Also, a new study has shown that RyRS2808A mice are not protected from myocardial infarction. Collectively, there is now a clear consensus in the published literature showing that dysregulated RyRs contribute to the altered Ca2+ regulatory phenotype of the failing heart, but PKA-mediated phosphorylation of RyRS2808 has little or no role in these alterations.
Proteinase inhibitor I accumulation in tomato suspension cultures : induction by plant and fungal cell wall fragments and an extracellular polysaccharide secreted into the medium.

Suspension-cultured cells of tomato accumulate proteinase Inhibitor I as the sucrose is depleted from 1% to less than 0.1% in the culture medium. Inhibitor I can be prematurely induced to accumulate in the cells by the addition to the medium of the proteinase inhibitor inducing factor, trigalacturonic acid, ethylene glycol chitin, or chitosan. In cultures grown in 0.6% initial sucrose with no inducers added, a uronic acid-rich extracellular polysaccharide appears in the medium during growth of the cells. This extracellular polysaccharide apparently contains an ;endogenous inducer' of Inhibitor I synthesis. When the partially purified polysaccharide is added to the culture medium, Inhibitor I accumulation is induced. Proteinase inhibitors also accumulate in tobacco and alfalfa suspension-cultured cells as the cell cultures age. As with the tomato cultures, a uronic acid-rich component(s) appears in the media prior to inhibitor accumulation. These data suggest that an endogenous inducer may be activating proteinase inhibitor genes through a similar mechanism in all three types of cells.
The Impact of Switching to a Rapid Release Cycle on the Integration Delay of Addressed Issues - An Empirical Study of the Mozilla Firefox Project

The release frequency of software projects has increased in recent years. Adopters of so-called rapid release cycles claim that they can deliver addressed issues (i.e., bugs, enhancements, and new features) to users more quickly. However, there is little empirical evidence to support these claims. In fact, in our prior work, we found that code integration phases may introduce delays in rapidly releasing software - 98% of addressed issues in the rapidly releasing Firefox project had their integration delayed by at least one release. To better understand the impact that rapid release cycles have on the integration delay of addressed issues, we perform a comparative study of traditional and rapid release cycles. Through an empirical study of 72,114 issue reports from the Firefox system, we observe that, surprisingly, addressed issues take a median of 50 days longer to be integrated in rapid Firefox releases than the traditional ones. To investigate the factors that are related to integration delay in traditional and rapid release cycles, we train regression models that explain if an addressed issue will have its integration delayed or not. Our explanatory models achieve good discrimination (ROC areas of 0.81-0.83) and calibration scores (Brier scores of 0.05-0.16). Deeper analysis of our explanatory models indicates that traditional releases prioritize the integration of backlog issues, while rapid releases prioritize issues that were addressed during the current release cycle. Our results suggest that rapid release cycles may not be a silver bullet for the rapid delivery of addressed issues to users.
In vitro regeneration system in brinjal (Solanum melongena L.) for stress tolerant somaclone selection

Brinjal is the second most important vegetable crop after potato in Bangladesh in respect of total areas and third in production. It also plays a vital role in the national economy as a cash crop. An experiment was conducted with two cultivars of brinjal namely Jhumky and Islampuri to observe the callus induction ability of different explants-shoot tip, hypocotyl and midrib in MS basal media supplemented with different concentrations and combinations of growth regulators. The rate of callus induction from shoot tip, hypocotyl and midrib were 82.78%, 74.88% and 78.71%, respectively. Highest rate of callus induction was found in shoot tip. Variety Islampuri showed higher rate of callus induction (80.62%). Among the treatments 2mg/l NAA showed the best performance in callus proliferation. Cytokinin (0.5 mg/l BAP) showed highest percentage of shoot regeneration (57.13%). For root induction, MS basal medium was proved to be better treatment for average number (12-15) of roots. The survival rate of transferred regenerated plantlets after hardening was higher in Jhumky (80%). Regenerated plantlets from callus of both the varieties exhibited 4-9 times higher proline, 2-3 times lower vitamin C and 2-3 times higher iron (Fe) content compared to their seed derived seedlings. This experiment showed that it is possible to develop shoot and fruit borer tolerance brinjal genotypes through somatic embryogenesis that was selected based on biochemical markers within the very short period of time. These findings will be helpful for further selection of the selected variants in field condition in the next phase of the study.
Age-related Ebv-associated B-cell Lymphoproliferative Disorders Constitute a Distinct Clinicopathologic Group: a Study of 96 Patients Clinical Oncology

Purpose: We have recently reported EBV+ B-cell lymphoproliferative disorders (LPD) occurring predominantly in elderly patients, which shared features of EBV+ B-cell neoplasms arising in the immunologically deteriorated patients despite no predisposing immunodeficiency and were named as senile or age-related EBV+ B-cell LPDs.To further characterize this disease, age-related EBV+ B-cell LPDs were compared with EBV-negative diffuse large B-cell lymphomas (DLBCL). Experimental Design: Among 1,792 large B-cell LPD cases, 96 EBV+ cases with available clinical data set were enrolled for the present study. For the control group, 107 patients aged over 40 years with EBV-negative DLBCL were selected.We compared clinicopathologic data between two groups and determined prognostic factors by univariate and multivariate analysis. Results: Patients with age-related EBV+ B-cell LPDs showed a higher age distribution and aggressive clinical features or parameters than EBV-negative DLBCLs: 44% with performance status >1, 58% with serum lactate dehydrogenase level higher than normal, 49% with B symptoms , and higher involvement of skin and lung. Overall survival was thus significantly inferior in age-related EBV+ group than in DLBCLs. Univariate and multivariate analyses further identified two factors, B symptoms and age older than 70 years, independently predictive for survival. A prognostic model using these two variables well defined three risk groups: low risk (no adverse factors), intermediate risk (one factor), and high risk (two factors). Conclusions: These findings suggest that age-related EBV+ B-cell LPDs constitute a distinct group, and innovative therapeutic strategies such as EBV-targeted T-cell therapy should be developed for this uncommon disease. Diffuse large B-cell lymphoma (DLBCL) is the largest category of aggressive lymphomas and regarded as a heterogeneous group of lymphomas in terms of clinicopathologic profiles and biological properties (1). Recent advance in the lymphoma research shed the light on the distinct subgroups such as de novo CD5+ DLBCL (2), intravascular large B-cell lymphoma (Asian variant; ref. 3), primary effusion lymphoma (4), and pyothorax-associated lymphoma (5) under the nosologic term of DLBCL. In addition, we have recently identified a series of elderly patients of EBV+ B-cell lymphoproliferative disorders (LPD) and/or large-cell lymphomas without predisposing immunodeficien-cies and named those senile or age-related EBV+ B-LPDs (6). EBV is a ubiquitous g-herpesvirus that infects more than 90% of worldwide adult population (7, 8). In contrast to its high prevalence, EBV is also well recognized as an apparent oncogenic agent (9). It transforms B cells into lymphoblastoid cell lines in vitro, and many human cancers, including Burkitt lymphoma (BL) …
Connectivity estimation of neural networks using a spike train kernel

Estimating the connectivity strength based on the signals observed at each node of a network is an important task in neural network analysis. One notable example is estimating the connectivity of a biological neural network using spikes (i.e., action potentials) observed at electrodes. The research presented in this paper introduces a novel method that estimates the underlying connectivity of a given neural network based on a similarity measure applied to spike trains. Specifically, we use a normalized positive definite kernel defined on spike trains to estimate network connectivity. The proposed method was evaluated in the context of synthetic and real data. The generation of synthetic data is based on a CERM (Coupled Escape-Rate Model), which is known to generate spike trains of various types by tuning a few parameters. We also analyzed real data recorded from the visual cortex of an anaesthetized cat. The results showed that our method provides an effective way of estimating connectivity when spike trains are the only observable information.
A Performance-Aware Low-Quiescent Headphone Amplifier in 65-nm CMOS

A low-quiescent high-performance class-AB headphone amplifier is presented. The effect of the input-referred offset on the quiescent power of audio power amplifier (APA) that drives very small resistive load is described and analyzed. A digitally assisted offset calibration-based APA topology together with improved frequency compensation is proposed. This permits the use of low quiescent power and small compensation capacitance. Implemented in 65-nm CMOS technology, the amplifier occupies an area of 0.15 mm<sup>2</sup> and consumes 0.4 mW at ±1 V supplies. At the load of 16 <inline-formula> <tex-math notation="LaTeX">$\Omega $ </tex-math></inline-formula>//200 pF, the gain-bandwidth product is 1.78 MHz using a total compensation capacitance of 8.5 pF. Other performance metrics are measured with −89-dB total harmonic distortion (THD+N), 93.5-dB signal-to-noise ratio, 84-dB power supply rejection ratio (PSRR+), and 105-dB PSRR– @217 Hz. It can deliver a peak power of 35 mW (1.5 <inline-formula> <tex-math notation="LaTeX">$V_{\mathrm{ pp}}$ </tex-math></inline-formula> swing) to the above load, yielding the best figure-of-merit (FOM) = (peak load power/quiescent power) and the best FOM2 = [peak load power/quiescent power <inline-formula> <tex-math notation="LaTeX">$\ast $ </tex-math></inline-formula> (THD+N)%] with respect to other reported representative works.
Outer Membrane c-Type Cytochromes Required for Fe(III) and Mn(IV) Oxide Reduction in Geobacter sulfurreducens

ABSTRACT The potential role of outer membrane proteins in electron transfer to insoluble Fe(III) oxides by Geobacter sulfurreducens was investigated because this organism is closely related to the Fe(III) oxide-reducing organisms that are predominant in many Fe(III)-reducing environments. Two of the most abundant proteins that were easily sheared from the outer surfaces of intact cells were c-type cytochromes. One, designated OmcS, has a molecular mass of ca. 50 kDa and is predicted to be an outer membrane hexaheme c-type cytochrome. Transcripts for omcS could be detected during growth on Fe(III) oxide, but not on soluble Fe(III) citrate. The omcS mRNA consisted primarily of a monocistronic transcript, and to a lesser extent, a longer transcript that also contained the downstream gene omcT, which is predicted to encode a second hexaheme outer membrane cytochrome with 62.6% amino acid sequence identity to OmcS. The other abundant c-type cytochrome sheared from the outer surface of G. sulfurreducens, designated OmcE, has a molecular mass of ca. 30 kDa and is predicted to be an outer membrane tetraheme c-type cytochrome. When either omcS or omcE was deleted, G. sulfurreducens could no longer reduce Fe(III) oxide but could still reduce soluble electron acceptors, including Fe(III) citrate. The mutants could reduce Fe(III) in Fe(III) oxide medium only if the Fe(III) chelator, nitrilotriacetic acid, or the electron shuttle, anthraquinone 2,6-disulfonate, was added. Expressing omcS or omcE in trans restored the capacity for Fe(III) oxide reduction. OmcT was not detected among the sheared proteins, and genetic studies indicated that G. sulfurreducens could not reduce Fe(III) oxide when omcT was expressed but OmcS was absent. In contrast, Fe(III) oxide was reduced when omcS was expressed in the absence of OmcT. These results suggest that OmcS and OmcE are involved in electron transfer to Fe(III) oxides in G. sulfurreducens. They also emphasize the importance of evaluating mechanisms for Fe(III) reduction with environmentally relevant Fe(III) oxide, rather than the more commonly utilized Fe(III) citrate, because additional electron transfer components are required for Fe(III) oxide reduction that are not required for Fe(III) citrate reduction.