Miracle-dz/UniFAR-FTUs huggingface dataset:
The safety and efficacy of pazopanib prior to planned nephrectomy in metastatic clear cell renal cancer.

427 Background: The safety and efficacy of upfront pazopanib, prior to nephrectomy in metastatic clear cell renal cancer (mCRC), has not been prospectively evaluated. The toxicity profile of pazopanib potentially makes it an attractive agent in this setting. METHODS A single arm phase II study (PANTHER 2009-016675-29) evaluated 12-14 weeks of pazopanib prior to planned nephrectomy in untreated patients with metastatic clear cell renal cancer. Patients had MSKCC intermediate and poor risk disease. Pazopanibwas stopped for a minimum of 16 days during nephrectomy. FDG-PET and DCEMRI were performed on a subgroup of patients. The study follows a Simon 2 stage design and we present the results of the initial stage(n=34). RESULTS Overall 30 (88%) of patients obtained clinical benefit (by RECIST) prior to surgery. The partial response rate of the primary tumor was 21% by RECIST. No patients became inoperable due to local progression of disease. A nephrectomy was performed in 25 (74%) of patients. The reasons for not having surgery were patient choice (n=5) and progression of disease (n=4). Delayed wound healing, a post operative bleed and a post operative death occurred in 1patient each (4%). The median blood loss, hospital stay and surgical time were 350mls, 7 days and 180mins respectively. FDG-PET and DCE MRI responses were reported. CONCLUSIONS This interim analysis suggest nephrectomy after upfront pazopanib can be performed safely in mRCC and obtains control of disease in the majority of patients.
Preoperative thrombocytosis as a prognostic factor in endometrioid-type endometrial carcinoma

BACKGROUND The impact of preoperative thrombocytosis as a prognostic factor in endometrial carcinoma (EC) remains uncertain and has never been examined in Saudi Arabia. OBJECTIVES To determine the prevalence of preoperative thrombocytosis (platelet count >400 000/μL), and its prognostic significance for clinicopathological factors and survival in Saudi patients with endometrioid-type EC. DESIGN A retrospective cross-sectional study from January 2010 to December 2013. SETTING A referral tertiary healthcare institute. PATIENTS AND METHODS Patients who underwent staging surgery for primary endometrioid-type EC were retrospectively analyzed for perioperative details: age, preoperative platelet count, International Federation of Gynecology and Obstetrics (FIGO) stage, endometrioid grade, recurrence, disease-free survival (DFS) and overall survival (OS). Survival analysis was conducted using Kaplan-Meier estimates and a Cox proportional hazards model. MAIN OUTCOME MEASURES Prevalence of preoperative thrombocytosis, DFS and OS. RESULTS: In 162 patients who met inclusion criteria, the frequency of preoperative thrombocytosis was 8.6% (n=14). Patients with advanced FIGO disease (stages III–IV) and recurrence had significantly higher mean preoperative platelet counts than patients with early FIGO disease (stages I–II) and no recurrence (P=.0080 and P=.0063, respectively). Patients with thrombocytosis had statistically significant higher rates of advanced FIGO stages III–IV disease, unfavorable grades II–III endometrioid histology and recurrence than patients with preoperative platelet counts ≤400 000/μL (P<.001, P<.0105 and P<.001, respectively). In a univariate analysis, patients with preoperative thrombocytosis had statistically lower mean DFS and OS rates than patients without thrombocytosis (P<.0001 and P<.0001, respectively). In a multivariate analysis, thrombocytosis was not an independent prognostic factor of DFS and OS. CONCLUSION The frequency of preoperative thrombocytosis is not uncommon. Also, preoperative thrombocytosis is associated with poor clinicopathological prognostic factors, and poor survival outcomes in a univariate but not multivariate analysis. LIMITATION The retrospective study design, sample size and lack of exploration of other clinicopathological factors.
Novel anaesthetic approach for surgical access and haemodynamic management during off-pump coronary artery bypass through a left thoracotomy

For myocardial revascularization on a beating heart through a thoracotomy, a properly deployed endobronchial blocker (EBB) provides ideal conditions for surgical access. In addition, adequate volume replacement to achieve optimal cardiac performance is a primary goal of haemodynamic management in patients undergoing off-pump coronary artery bypass grafting. To achieve both these ends, this case report describes the combined use of a left-sided EBB along with a volumetric pulmonary artery catheter in a patient who underwent a successful off-pump coronary artery bypass surgery through an anterolateral thoracotomy.
Production of nanohole/nanodot patterns on Si(001) by ion beam sputtering with simultaneous metal incorporation

We have established the conditions for which nanohole and nanodot patterns are produced on Si(001) surfaces by 1 keV Ar+ ion beam sputtering (IBS) at normal incidence with an alternating cold cathode ion source (ACC-IS). Nanohole patterns are produced within a narrow IBS window for low ion fluxes (<100 µA cm−2) and relatively low ion fluences (<1018 ions cm−2) whereas nanodot morphologies are produced above this window. The nanohole pattern is not stable after prolonged irradiation since it evolves to a nanodot morphology. Rutherford backscattering spectrometry (RBS) measurements show that nanohole patterns are produced when the metal content on the irradiated surfaces is higher (within (2.5–3.5 × 1015) atoms cm−2) than in the case of nanodots (<2.5 × 1015 atoms cm−2). The different metal content is related to the ACC-IS operation, since the set-up provides simultaneous incorporation of Fe and Mo on the target surface from the erosion of the cathodes and sample holder, respectively. The role of metal incorporation on pattern selectivity has been corroborated qualitatively by extending the results obtained with the ACC-IS to a standard Kaufman-type source. In order to gain further information on the metal effects, chemical analysis of the surface has been performed to complement the compositional RBS results, showing for the first time the relevant participation of metal silicides. Further outlook and a discussion regarding the role of metal incorporation are also given.
Vision without proprioception modulates cortico-spinal excitability during hand motor imagery.

Several studies have shown a cortico-spinal facilitation during motor imagery. This facilitation effect is weaker when the actual hand posture is incompatible with the imagined movement. To determine whether the source of this interference effect arises from online proprioceptive information, we examined transcranial magnetic stimulation (TMS)-induced motor-evoked potentials during motor imagery in the deafferented subject G.L. The patient and 7 control subjects were asked to close their eyes and imagine joining the tips of the thumb and the little finger while maintaining a hand posture compatible or incompatible with the imagined movement. Contrary to control subjects' performance, G.L. 's results show that the facilitation observed during motor imagery was independent of the hand posture. To examine how vision of the hand interacts with the imagery process, G.L. and control subjects performed the same task with the eyes open. Like control subjects, when G.L. looked at her hand, a greater facilitation was observed when her hand posture was compatible with the imagined movement than when it was incompatible. These results suggest that in the absence of proprioception, vision may facilitate or inhibit motor representations and support the idea that limb position in the brain is organized around multisensory representations.
Duration of competence and inducing capacity of blastomeres in notochord induction during ascidian embryogenesis

Notochord cells in ascidian embryos are formed by the inducing action of cells of presumptive endoderm, as well as neighboring presumptive notochord, at the 32‐cell stage. Studies of the timing of induction using recombinations of isolated blastomeres have suggested that notochord induction must be initiated before the decompaction of blastomeres at the 32‐cell stage and is completed by the 64‐cell stage. However, it is not yet clear how the duration of notochord induction is strictly limited. In the present paper, the aim was to determine in detail when the presumptive notochord blastomeres lost their competence to respond, and when the presumptive endoderm blastomeres produced inducing signals for the notochord. Presumptive notochord blastomeres and presumptive endoderm blastomeres were isolated from early 32‐cell embryos, and were heterochronously recombined at various stages ranging from the early 32‐cell stage to the 64‐cell stage. Presumptive notochord blastomeres could respond to inductive signals at the early 32‐cell stage, and started to lose their responsiveness at the decompaction stage. By contrast, the presumptive endoderm blastomeres persisted in their inducing capacity even at the 64‐cell stage. These observations suggest that the loss of competence in presumptive notochord blastomeres limits the duration of notochord induction in intact ascidian embryos.
Phasic muscle activity in sleep and clinical features of Parkinson disease

The absence of atonia during rapid eye movement (REM) sleep and dream‐enactment behavior (REM sleep behavior disorder [RBD]) are common features of sleep in the alpha‐synucleinopathies. This study examined this phenomenon quantitatively, using the phasic electromyographic metric (PEM), in relation to clinical features of idiopathic Parkinson disease (PD). Based on previous studies suggesting that RBD may be prognostic for the development of later parkinsonism, we hypothesized that clinical indicators of disease severity and more rapid progression would be related to PEM.
Pressor and renal vasoconstrictor effects of NG-nitro-L-arginine as affected by blockade of pressor mechanisms mediated by the sympathetic nervous system, angiotensin, prostanoids and vasopressin.

Inhibitors of nitric oxide (NO) synthesis increase blood pressure and decrease regional blood flow. We investigated whether blockade of the renin-angiotensin, sympathetic nervous, prostaglandin or vasopressin systems attenuates the effects of the NO synthesis inhibitor NG-nitro-L-arginine (L-NOARG) on mean arterial pressure and renal blood flow in anesthetized male Sprague-Dawley rats. Treatment with L-NOARG (10 mg kg-1, i.v. bolus plus infusion at 20 mg kg-1 hr-1) increased mean arterial pressure from 113 +/- 2 to 133 +/- 4 mm Hg, decreased renal blood flow from 7.7 +/- 0.6 to 4.3 +/- 0.6 ml min-1 g-1 and increased renal vascular resistance from 15.8 +/- 1.8 to 36.9 +/- 6.1 mm Hg/ml min-1 g-1. These effects were attenuated in rats pretreated with L-arginine to interfere with the inhibitory action of L-NOARG on NO synthesis, but not in rats pretreated with D-arginine. Acetylcholine did not relax aortic rings taken from rats treated with L-NOARG, consistent with inhibition of NO-mediated vasorelaxation. The pressor and renal vasoconstrictor effects of L-NOARG were not impaired in rats separately pretreated with either chlorisondamine, captopril, prazosin, indomethacin or d(CH2)5Tyr(Me)AVP, or in rats pretreated with chlorisondamine, captopril and indomethacin in combination. Collectively, these data argue against significant contribution of the sympathetic nervous system, the renin-angiotensin system, vasopressor prostanoids or vasopressin to the mechanisms of L-NOARG-induced elevation of mean arterial pressure and renal vasoconstriction in anesthetized rats.
Regulated large-scale nucleosome density patterns and precise nucleosome positioning correlate with V(D)J recombination

Significance Immunoglobulin and T-cell receptor genes are assembled in lymphoid cells from gene fragments by the process known as V(D)J recombination, which is initiated by the recombination activating gene (RAG)1/RAG2 recombinase. To ensure that recombination occurs only in the correct cell type and at the right developmental stage, multiple layers of regulation are necessary, including specific modifications of chromatin. We show that nucleosome positioning is another important factor in this regulation. Developmentally regulated changes in nucleosome positioning help to guide RAG1/RAG2 to the correct sites in recombinationally active cells. These changes occur on the scale of hundreds of kilobases, a form of regulation not typically seen in the rest of the mammalian genome. We show that the physical distribution of nucleosomes at antigen receptor loci is subject to regulated cell type-specific and lineage-specific positioning and correlates with the accessibility of these gene segments to recombination. At the Ig heavy chain locus (IgH), a nucleosome in pro-B cells is generally positioned over each IgH variable (VH) coding segment, directly adjacent to the recombination signal sequence (RSS), placing the RSS in a position accessible to the recombination activating gene (RAG) recombinase. These changes result in establishment of a specific chromatin organization at the RSS that facilitates accessibility of the genomic DNA for the RAG recombinase. In contrast, in mouse embryonic fibroblasts the coding segment is depleted of nucleosomes, which instead cover the RSS, thereby rendering it inaccessible. Pro-T cells exhibit a pattern intermediate between pro-B cells and mouse embryonic fibroblasts. We also find large-scale variations of nucleosome density over hundreds of kilobases, delineating chromosomal domains within IgH, in a cell type-dependent manner. These findings suggest that developmentally regulated changes in nucleosome location and occupancy, in addition to the known chromatin modifications, play a fundamental role in regulating V(D)J recombination. Nucleosome positioning—which has previously been observed to vary locally at individual enhancers and promoters—may be a more general mechanism by which cells can regulate the accessibility of the genome during development, at scales ranging from several hundred base pairs to many kilobases.
Significance of surgical treatment in multimodal therapy for stage IV highly advanced gastric cancer.

BACKGROUND/AIMS The purpose of this study was to evaluate the efficacy of surgical treatment following a response to chemotherapy to improve stage IV gastric cancer and to identify the factors contributing to survival benefit. METHODOLOGY In total, 148 patients with cStage IV gastric cancer were treated with S-1 and CDDP. We retrospectively evaluated the factors contributing to a survival benefit and the significance of surgical treatment. RESULTS The 148 cStage IV patients included 107 males with a median age of 61 years. The overall response rate was 54.7%. After chemotherapy, 97 patients underwent surgery. R0 resection was successfully performed in 51 (52.6%) patients. The overall median survival time (MST) of the patients was 16.8 months, with a 5YSR of 16.4%. The MST of patients who went on to receive surgery was 22.5 months, and the 5YSR was 19.6%. In the multivariate analysis of 97 patients who underwent surgery, R0 resection, lymph node dissection of D2/D3 and obtaining a CR/PR from chemotherapy were the only independently prognostic factors. CONCLUSIONS The use of multi-modal treatment, including surgical treatment, at an appropriate time was well tolerated and effective for patients with stage IV gastric cancer.
$k$ -factor Test Voltage Function for Oscillating Lightning Impulses in Nonhomogenous Air Gaps

The k-factor function, called the test voltage function, in present standards IEEE Standard 4-2013 and IEC 60060-1, was determined years ago for voltages not higher than 100 kV and with relative overshoots around 15%. This paper presents the results of k-factor tests carried out for greater voltages up to +1.32 MV (equivalent to air-gap distances d = 2.5 m) and many test conditions. These test conditions are relative overvoltages, β' up to 35%, different damping ratios: from δ = 0 (overshoot) to δ =35% (oscillating waveform), and different electrical configurations of a nonhomogenous electric field using air gap factors K = 1 (rod plane) up to K =1,45 (rod conductor). The results show that the present k-factor function stated in both standards does not represent insulation behavior for large air-gap distances when the gap factor K is around 1. Only when the gap factor K increases to 2, are the experimental k-factor values closer to the standard k-factor function. A general formula for the k-factor, depending on the oscillation frequency, gap distance, and the electric-field nonhomogeneity, k (f, d ,K) is derived from the performed tests, taking also into account the k-factor results of the recent bibliography.
Functional Analysis of relA andrshA, Two relA/spoT Homologues ofStreptomyces coelicolor A3(2)

ABSTRACT Deletion of the (p)ppGpp synthetase gene, relA, ofStreptomyces coelicolor A3(2) results in loss of production of the antibiotics actinorhodin (Act) and undecylprodigiosin (Red) and delayed morphological differentiation when the mutant is grown under conditions of nitrogen limitation. To analyze the role of (p)ppGpp as an intracellular signaling molecule for the initiation of antibiotic production, several C-terminally deleted derivatives of S. coelicolor relA that could potentially function in the absence of ribosome activation were placed under the control of the thiostrepton-inducible tipA promoter. While 0.82- and 1.28-kb N-terminal segments failed to restore (p)ppGpp and antibiotic production upon induction in a relA null mutant, 1.46- and 2.07-kb segments did. Under conditions of phosphate limitation, deletion of relA had little or no effect on Act or Red synthesis, potentially reflecting an alternative mechanism for ppGpp synthesis. A second S. coelicolor RelA homologue (RshA, with 42% identity to S. coelicolor RelA) was identified in the genome sequence. However, deletion ofrshA had no effect on the ability of the relAmutant to make Act and Red when grown under conditions of phosphate limitation. While high-level induction oftipAp::rshA in the relAmutant resulted in growth inhibition, low-level induction restored antibiotic production and sporulation. In neither case, nor in therelA mutant that was grown under phosphate limitation and producing Act and Red, could (p)ppGpp synthesis be detected. Thus, a ppGpp-independent mechanism exists to activate antibiotic production under conditions of phosphate limitation that can be mimicked by overexpression of rshA.
Predicting Transfusion Requirements During Extracorporeal Membrane Oxygenation.

OBJECTIVE Patients requiring extracorporeal membrane oxygenation (ECMO) have a well-known bleeding risk and the potential for experiencing possibly fatal thromboembolic complications. Risk factors and predictors of transfusion requirements during ECMO support remain uncertain. The authors hypothesized that compromised organ function immediately before ECMO support will influence transfusion requirements. DESIGN A prospective observational study. SETTING A tertiary, single-institutional university hospital. PARTICIPANTS The study included 40 adult patients requiring ECMO for intractable cardiac and respiratory failure between July 2010 and December 2012. Blood samples were taken before initiation of ECMO (baseline), after 24 and 48 hours on ECMO, and 24 hours after termination of ECMO. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Independent of veno-arterial or veno-venous support, 26% of patients required≥2 packed red blood cells per day (PRBC/d) and 74% of patients required<2 PRBC/d during ECMO. Requirements of≥2 PRBC/d during ECMO support were associated with higher creatinine levels and lower prothrombin times (PT, %) at baseline and with impaired platelet function after 24 hours on ECMO. Platelet function, activated by thrombin receptor-activating peptide stimulation, decreased by 30% to 40% over time on ECMO. Receiver operating characteristic curve analysis showed cut-off values for creatinine of 1.49 mg/dL (sensitivity 70%, specificity 70%; area under the curve [AUC] 0.76, 95% confidence interval [CI] 0.58-0.94), for PT of 48% (sensitivity 80%, specificity 59%; AUC 0.69, 95% CI 0.50-0.87), and for thrombin receptor-activating peptide (TRAP) 32 U (sensitivity 90%, specificity 68%; AUC 0.76, 95% CI 0.59-0.93). CONCLUSIONS The results of this study demonstrated that increased creatinine levels and lower PT before ECMO and secondary impaired platelet function significantly increased transfusion requirement.
Choosing suitable variants of Differential Evolution and Particle Swarm Optimization for the optimization of a PI cascade control

Robust control is an intensively studied field in control theory where analytical solutions for robust control problems often lead to complicated control structures. On the other hand, for simple structures like the PI cascade control l here are no analytical solutions which leads to the need of easy-to-use optimization algorithms. Differential evolution and particle swarm optimization are well suited for this problem because of the real-valued representation of solutions, fast convergence behavior and ease of use. However, seven al variants exist for both algorithms, and from literature if does not become clear which one performs best. Therefore, in this paper several strategies of differential evolution an d different neighborhood topologies for particle swarm optimization are applied for the optimization of a PI cascade control. A performance comparison shows that both algorithms are able to solve this optimization problem but especially using differential evolution the quality of the best solution varies for different strategies.
Don’t Say That to ME: Opposition to Targeting in Weight-Centric Intervention Messages

ABSTRACT Obesity is a global health issue. Despite well-intentioned efforts by public institutions, traditional health promotion techniques often lead to offending those most in need of weight loss. For example, when Bryn Mawr College targeted overweight students to offer a free fitness and nutrition program, it was met with accusations of fat-shaming, indicating that weight-centric messages operate in a more complex sociocultural system than many public health concerns. To better understand reactions to weight-centric health messages, college-aged women evaluated the Bryn Mawr College e-mail. Using an embedded mixed-methods design, analysis revealed that reactions followed four positive themes, six negative themes, and one neutral theme. Statistical tests indicated that health literacy, feminist identification, body dissatisfaction, and body size discrepancy influenced evaluations of message offensiveness and effectiveness. Contrary to the recommendations of traditional behavior change research, these results indicate that audience segmentation and message tailoring may not be effective for promoting weight loss.