Miracle-dz/UniFAR-FTUs huggingface dataset:
Bevacizumab is an active agent for recurrent high-grade glioma, but do we need randomized controlled trials?

High-grade gliomas (HGGs), including glioblastoma, are a heterogeneous group of primary brain tumors, associated with devastating neurological sequelae and limited survival. In 2005, a randomized phase III study established postoperative radiotherapy and temozolomide as the standard of care for patients with resected, newly diagnosed glioblastoma. Despite this progress, almost all patients relapse and therapeutic options in the recurrent setting are limited. The optimum approach for recurrent HGG is challenging because of tumor resistance and the worsening performance status of the patients. As glioblastoma is a highly vascular tumor and has high levels of vascular endothelial growth factor, there has been interest in the use of the vascular endothelial growth factor targeting, monoclonal antibody bevacizumab. In a series of phase II studies, bevacizumab alone or with irinotecan showed improvements in tumor response, disease control, and survival compared with historical controls. These results led to the licensing of bevacizumab for glioblastoma in the USA, but a contrasting view was adopted by the European Medicines Agency, because of (deemed) modest response rates and lack of direct comparisons with other agents. Against this background, Gil and colleagues conducted a retrospective review of 130 patients with recurrent HGG treated with bevacizumab and irinotecan and showed an encouraging median progression-free survival of 5.1 months (95% confidence interval, 4.4–5.9) and a median overall survival of 9.0 months (95% confidence interval, 6.7–11.2), in agreement with other series. In this editorial, the context and implications of these results are discussed, with a particular focus on the possible need and design of randomized phase III trials.
Structural and Functional Diversity of Peptide Toxins from Tarantula Haplopelma hainanum (Ornithoctonus hainana) Venom Revealed by Transcriptomic, Peptidomic, and Patch Clamp Approaches*

Background: Spider venom is a complex mixture and contains over 400 venom peptides/species. Results: Highly abundant hypermutation, fragment insertion/deletion, and variable post-translational modifications were observed in venom gland, and the highly diverse toxins exhibit diverse functions. Conclusion: Spider toxins are abundant and variable, factors that work together to generate diverse bioactivities. Significance: Our study reveals the mechanism of structural and functional diversity of peptide toxins from Ornithoctonus hainana. Spider venom is a complex mixture of bioactive peptides to subdue their prey. Early estimates suggested that over 400 venom peptides are produced per species. In order to investigate the mechanisms responsible for this impressive diversity, transcriptomics based on second generation high throughput sequencing was combined with peptidomic assays to characterize the venom of the tarantula Haplopelma hainanum. The genes expressed in the venom glands were identified, and the bioactivity of their protein products was analyzed using the patch clamp technique. A total of 1,136 potential toxin precursors were identified that clustered into 90 toxin groups, of which 72 were novel. The toxin peptides clustered into 20 cysteine scaffolds that included between 4 and 12 cysteines, and 14 of these groups were newly identified in this spider. Highly abundant toxin peptide transcripts were present and resulted from hypermutation and/or fragment insertion/deletion. In combination with variable post-translational modifications, this genetic variability explained how a limited set of genes can generate hundreds of toxin peptides in venom glands. Furthermore, the intraspecies venom variability illustrated the dynamic nature of spider venom and revealed how complex components work together to generate diverse bioactivities that facilitate adaptation to changing environments, types of prey, and milking regimes in captivity.
Secular trend in stature in the Portuguese population (1904-2000)

The records of height of 995 101 18-year-old Portuguese males were analysed as well as the relation between localities of the subject's residence (districts) and final height. The sample includes all the Portuguese 18-year-old males born between 1966 and 1982 and examined between 1985 and 2000, in the north, centre and south of Portugal, representing all the social strata. Statistically significant differences ( p h 0.001) among the districts were found: males from Lisboa (172.79 cm) and Braga (172.67 cm), the most developed districts, are the tallest, and those from Madeira (170.67 cm), Castelo Branco, Leiria and Coimbra (171.31 cm) are the shortest. Comparing to published data from 1904, a positive secular trend in height was found. The average increase was 8.93 cm, which yields a rate of 0.99 cm per decade. This positive trend must be related to the general improvement in the population's standard living conditions that took place in Portugal mainly after the 1960s and 1970s, especially in terms of nutrition and the health system. However, taking into account the differences that still exist in mean height values between the districts, these results suggest that there are still great social inequalities in Portugal and the secular trend in height will continue for the Portuguese population in future decades.
Material based process model for linear noncircular coil winding processes with large wire gauge: Investigation of wire material influences on the winding process and compensation approaches

This paper comprises an overview of different simulation aspects for a material based process model approach and introduces considered model parameters. In order to consider all possible influences through the winding process, critical wire stress conditions, from wire feeding to stress intake while wire placement around the coil body edges, will be examined. The use of the developed model for different material determined aspects of the winding process will be discussed and possible counter-measures for avoidance or compensation of critical forces will be carried out. Synergies regarding new principles, like piezoelectric based wire brakes will be analyzed.
Chromosomal instability of fanconi anemia cells is not the consequence of a defective repair activity of the ribosomal protein S3.

Fanconi anemia (FA) is an autosomal recessive chromosomal breakage disorder characterized by developmental defects, hypersensitivity toward oxygen and DNA crosslinking agents, and susceptibility to cancer. An increased level of reactive oxygen intermediates and an increased level of 8-oxoguanine in FA cells point to a defective oxygen metabolism. Recent investigations showed that FA cells from several complementation groups have a reduced capacity to repair oxidatively damaged DNA. One major enzyme involved in the repair of oxidative DNA lesions is the ribosomal protein S3. Previous reports implied a role for the ribosomal protein S3 in DNA repair in FA cells. However, a more detailed analysis of the ribosomal protein S3 in FA cells from complementation groups A-E could not confirm this. DNA analysis and Western blot analysis did not show significant differences in ribosomal protein S3 between FA cells and cells from healthy individuals. Furthermore, even the overexpression of the ribosomal protein S3 did not reduce the chromosomal instability of FA cells.
A comprehensive comparative study of DGA based transformer fault diagnosis using fuzzy logic and ANFIS models

In this work, Dissolved gas Analysis (DGA) has been implemented using soft computing models namely fuzzy logic and Adaptive Neuro fuzzy inference system (ANFIS). DGA has developed as an effective tool for the identification of transformer incipient faults. A number of standards and procedures have evolved over the years making DGA more reliable and user friendly. A comparative study of the two models has been developed based on their ability to circumvent the limitations of the IEC 599 standard, Rogers ratio method and Doernenburg's method. The models have been tested using a reported fault database for their diagnostic capability. Results presented in this paper clearly indicate the superiority of the ANFIS model over the fuzzy system. The ANFIS model presents a reliable system with relative high degree accuracy. ANFIS model being very simple to develop can obviate the limitations of conventional methods of transformer fault diagnosis using DGA.
Dietary protein absorption of the small intestine in human neonates.

BACKGROUND The intestine plays a key role in the absorption of dietary proteins, which determines growth of human neonates. Bowel resection in the neonatal period brings loss of absorptive and protective surface and may consequently lead to malabsorption of dietary nutrients. However, there are no data on net dietary protein absorption of the small intestine in the period after intestinal surgery in human neonates. We therefore evaluated dietary feeding tolerance and quantified net dietary protein absorption capacity of the small intestine in human neonates in whom a temporary jejunostomy or ileostomy was created. METHODS Seventeen patients were included in the study. We collected small intestinal outflow fluid at the level of the enterostomy weekly for 24-48 hours during weeks 3 through 6 postoperatively. Protein levels in the intestinal outflow fluid were determined by bicinchoninic acid (BCA) assay. RESULTS In 14 patients, an enteral intake of >100 mL/kg/d was reached at a median of 17 days (range, 8-32 days) postoperatively. Three patients did not reach this level within the study period. Overall, the net dietary protein absorption capacity was 70%-90% of the total enteral protein intake. CONCLUSIONS This study demonstrates that the dietary protein absorption capacity of the small intestine is intact in most human neonates after intestinal surgery in a very critical period of their lives. Furthermore, our results do not support the use of hydrolyzed or elemental formula in newborns with an enterostomy to improve amino acid uptake.
Preservation of endothelium‐dependent relaxation in cholesterol‐fed and streptozotocin‐induced diabetic mice by the chronic administration of cholestyramine

1 Experiments were designed to investigate the effects of the low density lipoprotein (LDL)‐lowering drugs cholestyramine on serum LDL levels and endothelium‐dependent relaxation to acetylcholine (ACh) in cholesterol‐fed or streptozotocin (STZ)‐induced diabetic mice. 2 In aortic rings from control mice, ACh or A23187 caused concentration‐dependent relaxation. The relaxations caused by ACh or A23187 were significantly attenuated in aortic rings from cholesterol‐fed and STZ‐diabetic mice. The attenuated vasodilatation in both cholesterol‐fed and diabetic mice was returned to normal by chronic administration of cholestyramine. The endothelium‐independent relaxations of aortic rings induced by sodium nitroprusside (SNP) were not significantly different between control, cholesterol‐fed and STZ‐induced diabetic mice. 3 The increased LDL levels in cholesterol‐fed and diabetic mice were returned to normal by the chronic administration of cholestyramine. Chronic administration of cholestyramine had no effects on serum glucose levels. 4 These results suggest that attenuated endothelium‐dependent vasodilatations in both cholesterol‐fed and STZ‐diabetic mice are improved by the chronic administration of cholestyramine, and these effects are, at least in part, due to lowering serum LDL levels.
Imaging Photopolarimeter on Pioneer Saturn

An imaging photopolarimeter aboard Pioneer 11, including a 2.5-centimeter telescope, was used for 2 weeks continuously in August and September 1979 for imaging, photometry, and polarimetry observations of Saturn, its rings, and Titan. A new ring of optical depth < 2 x 10–3 was discovered at 2.33 Saturn radii and is provisionally named the F ring; it is separated from the A ring by the provisionally named Pioneer division. A division between the B and C rings, a gap near the center of the Cassini division, and detail in the A, B, and C rings have been seen; the nomenclature of divisions and gaps is redefined. The width of the Encke gap is 876 � 35 kilometers. The intensity profile and colors are given for the light transmitted by the rings. A mean particle size ≲ 15 meters is indicated; this estimate is model-dependent. The D ring was not seen in any viewing geometry and its existence is doubtful. A satellite, 1979 S 1, was found at 2.53 � 0.01 Saturn radii; the same object was observed ∼ 16 hours later by other experiments on Pioneer 11. The equatorial radius of Saturn is 60,000 � 500 kilometers, and the ratio of the polar to the equatorial radius is 0.912 � 0.006. A sample of polarimetric data is compared with models of the vertical structure of Saturn's atmosphere. The variation of the polarization from the center of the disk to the limb in blue light at 88� phase indicates that the density of cloud particles decreases as a function of altitude with a scale height about one-fourth that of the gas. The pressure level at which an optical depth of 1 is reached in the clouds depends on the single-scattering polarizing properties of the clouds; a value similar to that found for the Jovian clouds yields an optical depth of 1 at about 750 millibars.
Underutilization of Aldosterone Antagonists in Heart Failure

Background: Treatment with an aldosterone antagonist (AA) has been shown in multiple trials to reduce heart failure (HF)–related morbidity, mortality, and hospital readmission. American College of Cardiology Foundation (ACCF) and American Heart Association (AHA) treatment guidelines recommend the use of an AA in all HF patients with an ejection fraction ≤35% and no known contraindication. Several studies have documented underuse of AA. Objectives: To determine the proportion of patients who received AA therapy consistent with the ACCF/AHA guidelines. Secondary objectives included determining the proportion of patients who received an AA inconsistent with guidelines and 30- and 90-day readmission rates. Methods: A retrospective chart review was conducted of patients admitted to an inner city academic medical center with a diagnosis of HF between August 16, 2011, and June 5, 2013. Results: A total of 346 HF admissions (87.6% African American) were evaluated. Use of an AA at discharge was consistent with guidelines in 31% of patients. A total of 121 patients (35%) were discharged on an AA. Among the remaining 225 patients who were not discharged on an AA, 170 (75.6%) had no contraindication to therapy. Sixty-one patients were readmitted within 30 days, and a total of 108 patients were readmitted within 90 days. There were no significant differences in readmission rates between patients who were discharged on AA therapy and those who were not. Conclusion: AAs are still underutilized in the treatment of HF.
Unmanipulated HLA‐mismatched/haploidentical peripheral blood stem cell transplantation for high‐risk hematologic malignancies

BACKGROUND: Haploidentical hematopoietic stem cell transplantation (HSCT) has been increasingly applied in high‐risk hematologic patients due to the absence of HLA‐matched donors. The aim of this study was to investigate the efficacy and safety of unmanipulated haploidentical allogeneic peripheral blood stem cells transplantation (PBSCT) for hematologic malignancies.
EGF‐stimulated signaling by means of PI3K, PLCγ1, and PKC isozymes regulates branching morphogenesis of the fetal mouse submandibular gland

Branching morphogenesis of fetal mouse submandibular glands (SMGs) partly depends on the epidermal growth factor (EGF) receptor that triggers at least three intracellular signaling pathways involving (1) the mitogen‐activated protein kinases ERK‐1/2, (2) phospholipase Cγ1 (PLCγ1), and (3) phosphatidylinositol‐3‐kinase (PI3K). PLCγ1 directly activates protein kinase C (PKC) isozymes; PI3K stimulates protein kinase B (PKB, also known as Akt), which ultimately activates PKCs and other proteins. We reported that the pattern of phosphorylation of ERK‐1/2 in response to EGF in SMGs varies with fetal age and that blockade of EGF‐stimulated ERK‐1/2 signaling partially inhibits branching (Kashimata et al. [2000] Dev. Biol. 220:183–196). Here, we report on components of the PLCγ1, PI3K, and PKC families of signaling molecules in fetal SMGs from the 13th day of gestation to postnatal ages. Western blotting revealed that (1) PLCγ1 is present from E13 to E18 but drops off precipitously to negligible levels on the day of birth and thereafter, and (2) PI3K, PKB(Akt), and several PKC isozymes are expressed from E13 onward through adult life. Both PLCγ1 and PI3K are phosphorylated in response to EGF. Inhibition of PI3K by LY294002 inhibited EGF‐stimulated branching, but inhibition of PLCγ1 by U73122 had no effect. Western blotting showed that the concentrations of 8 PKC isozymes vary with age in the fetal and postnatal SMG. However, general inhibition of PKCs by Calphostin C or specific inhibition of PKCα or of PKCϵ by Gö6976 or Ro‐32‐0432, respectively, increased EGF‐stimulated branching. Calphostin C also increased EGF‐stimulated phosphorylation of ERK‐1/2. These findings indicate that signaling from the EGF receptor in the fetal mouse SMG varies with development and triggers stimulatory effects by means of ERK‐1/2 and PI3K but inhibitory effects by means of PKC isozymes. Developmental Dynamics 227:216–226, 2003. © 2003 Wiley‐Liss, Inc.
A 3 Gb/s 64-QAM E-band direct-conversion transmitter in 40-nm CMOS

This paper describes a fully integrated E-band transmitter (TX) in 40-nm CMOS. Circuit, layout and calibration techniques are presented to suppress the LO feed-through (LOFT) and I/Q imbalance over both 71-76 and 81-86 GHz bands. A systematic design methodology is proposed for the millimeter-wave poly-phase filter (PPF) to achieve lowest I/Q imbalance with minimum EM simulations. The 40-nm E-band transmitter achieves a measured output power of 12 dBm and TX efficiency of 15% with about 15 GHz bandwidth. Measured from 3 chips, the transmitter features an un-calibrated I/Q imbalance of less than -30 dB from 62.5 to 85.5 GHz. The calibration circuits further reduce the I/Q imbalance by 3-5 dB and ensure the LOFT less than -30 dBc over more than 30 dB output dynamic range. The presented TX achieves 3-Gb/s 64-QAM across the complete E-band.
Individual differences in endogenous pain modulation as a risk factor for chronic pain

This review summarizes evidence, primarily from recent human studies, indirectly supporting a novel hypothesis: that the assessment of healthy individuals’ responses to standardized noxious stimuli in a controlled laboratory environment has important implications for the later risk of developing a broad spectrum of chronically painful conditions. Descriptions of many chronic pain syndromes note that the disorder (e.g., fibromyalgia, headache, complex regional pain syndrome) is associated with hypersensitivity to pain and with reduced endogenous inhibition of pain, implying that an individual’s processing of pain-related information changes with the onset of the syndrome. However, pain sensitivity and pain-inhibitory capacity are normally distributed along a wide continuum in the general population, and recent evidence suggests that heightened baseline pain sensitivity and reduced basal pain-inhibitory processing place individuals at greater risk for experiencing severe, acute, clinical pain (e.g., postoperative pain). More controversial is the hypothesis that such individual-difference characteristics confer risk for, or protection against, chronic pain; although only a single prospective study has been published, substantial indirect evidence supports the contention that greater basal pain sensitivity and reduced pain-inhibitory capacity may act as a diathesis for chronic pain. Long-term cohort studies are necessary to test this hypothesis; such research could yield insight into the nature of chronic pain and permit greater precision in selecting high-risk individuals for chronic pain prevention research.
A Residue-to-Binary Converter for the Extended Four-Moduli Set $\{2^{n}-1, 2^{n}+1, 2^{2n}+1, 2^{2n+p}\} $

This brief presents a residue-to-binary converter for the moduli set <inline-formula> <tex-math notation="LaTeX">$\{2^{n}-1, 2^{n}+1, 2^{2n}+1, 2^{2n+p}\} $ </tex-math></inline-formula>, where <inline-formula> <tex-math notation="LaTeX">$n$ </tex-math></inline-formula> is a positive integer and <inline-formula> <tex-math notation="LaTeX">$0\leq p \leq n-2 $ </tex-math></inline-formula>. The converter consists of three simplified <inline-formula> <tex-math notation="LaTeX">$4n$ </tex-math></inline-formula>-bit carry-save adders (CSAs) along with a modulo <inline-formula> <tex-math notation="LaTeX">$(2^{4n}-1) $ </tex-math></inline-formula> adder. The main contribution of this brief is reducing the requirements of the proposed CSA network, which has impacted the area, delay, power and energy. Compared with four-moduli and five-moduli sets that have the dynamic range <inline-formula> <tex-math notation="LaTeX">$2^{v}(2^{4n}-1) $ </tex-math></inline-formula>, where <inline-formula> <tex-math notation="LaTeX">$ v=n {~\mbox {or }} 2n$ </tex-math></inline-formula>, the proposed converter resulted in the average area, delay, power, and energy reductions of 22.7%, 9.2%, 17.8%, and 24.5%, respectively. Moreover, the throughput rate per unit area has been improved by an average of 48.7%.
Extracellular glutamate levels increase with age in the lateral striatum: Potential involvement of presynaptic D‐2 receptors

In the lateral striatum of aged rats, dopamine D‐2 receptor density is reduced and glutamate tissue content is elevated. D‐2 receptor agonists have been shown to inhibit stimulated glutamate release. In the present study, microdialysis was used to investigate a potential role for D‐2 receptors in the modulation of striatal glutamate efflux from 4‐, 12‐, 18‐, and 24–26‐month‐old Fischer 344 rats. Extracellular basal glutamate concentrations significantly increased as a function of age in the lateral, but not medial, striatum. Neither the D‐2 agonist, LY 163502, nor the D‐2 antagonist, sulpiride, influenced basal glutamate efflux, suggesting that the dopaminergic system is not involved in the observed age‐related increase in extracellular basal glutamate levels. In contrast to basal efflux, potassium‐evoked glutamate release was not altered with age. However, LY 163502 significantly inhibited stimulated glutamate release in 4‐month‐old rats. This inhibitory action was not observed at any other age. Sulpiride alone did not alter stimulated glutamate release, but it did block the inhibitory effect of LY 163502 in the 4‐month‐old rats. These results provide in vivo evidence for an age‐related functional loss in the modulation of striatal glutamate release by dopamine D‐2 receptors in addition to increased basal glutamate efflux, which is not related to D‐2 receptor modulation. Such mechanisms could be important in the pathophysiology of striatal cell death during aging and age‐related neurodegenerative diseases. © 1993 Wiley‐Liss, Inc.