nils-herrmann/clean_scirepeval huggingface dataset:
Tension testing in adherent cells

L ike soloing rock climbers, adherent cells need a good handhold to survive. Ma et al. now identify an adaptor protein that monitors the cell's grip and signals death if the grip fails. Death following detachment, known as anoikis, is a form of programmed cell death that ensures the disposal of displaced adherent cells. Lack of anoikis is thought to give cells metastatic potential. A number of survival factors have been identifi ed that are activated by integrin attachment to the extracellular matrix. Binding to soluble matrix fragments, rather than to a fi xed matrix, does not prevent anoikis. This difference suggests that mechanical tension is also being measured. Inside the cell, integrins associate with signaling adaptor proteins of the Shc family. One family member, p66 Shc , has been suggested to promote apoptosis. The team now shows that an epithelial cell line that resists anoikis does not express p66 Shc. Giving these cells back some p66 Shc reestablished detachment-induced death. Normal epithelial and endothelial cells express p66 Shc. Thus, p66 Shc must only trigger death upon cell detachment. p66 Shc did not induce anoikis by the same mechanism as it induces apoptosis. For apoptosis, p66 Shc enters mitochondria. But for anoikis, p66 Shc associated with integrins and activated the actin cytokeleton regulator RhoA. RhoA increases tension between cell attachment points by inducing stress fi ber formation. Inhibiting contraction of these fi bers, the team showed, curbed anoikis. The authors therefore suggest that the cell continuously checks its tension by contracting its stress fi bers—like checking from the inside of a tent whether the pegs are secure. If the cell contracts easily, then p66 Shc signals that external anchors are missing and that, for this cell, the camping trip is over. I n times of stress, cells reduce translation to conserve resources. Hoyle et al. now report that many of the backed-up untranslated mRNAs hang out in a new type of cytoplasmic granule called EGP bodies. The stress of glucose starvation in yeast abruptly slows translation. So Hoyle et al. wondered what happens to the stalled translation machinery. They discovered that three translation factors, eIF4E, eIF4G, and Pab1p (E, G, and P), huddled together into four or fi ve cytoplasmic foci. The binding of E, G, and P to untranslated mRNAs was thought to commit the transcripts to translation. But when the translation factors formed quiescent foci, the mRNAs went …
Prospective, randomized study of coil embolization versus Surefire infusion system during yttrium-90 radioembolization with resin microspheres.

To compare standard coil embolization versus the use of an antireflux microcatheter (ARM) in patients undergoing planning angiography before selective internal radiation therapy (SIRT).



A prospective, single-center trial was performed in which 30 patients were randomly assigned to undergo SIRT with coil embolization or the use of an ARM. The coil group underwent detachable coil embolization of nontarget vessels, and the ARM group underwent infusion of macroaggregated albumin with use of an ARM system, without coil embolization. Single-photon emission computed tomography (CT)/CT was then performed to assess for nontarget distribution. The primary endpoint was fluoroscopy time during planning angiography. Secondary endpoints included deployment time, total procedure time, radiation dose-area product, contrast agent used, and adverse events. Endpoints were evaluated during planning angiography and SIRT.



Over a 9-month period, 30 consecutive patients were randomized at a 1:1 ratio between coil embolization and ARM groups. Technical success rates were 100% in both groups. Mean fluoroscopy time was significantly reduced in the ARM group versus the coil embolization group (1.8 min [range, 0.4-4.9 min] vs 6.0 min [range, 1.9-15.7 min]; P = .002). The planning procedure time (P < .001), deployment time (P < .001), dose-area product (P = .04), and amount of contrast agent used (P < .001) were also significantly less in the ARM group than in the coil embolization group. No nontarget distribution was detected in either group. There was no difference between groups in dose delivered on the day of SIRT (P = .71). There were no major or minor adverse events at 30 days.



The use of an ARM during planning angiography can significantly reduce fluoroscopy time, procedure time, and radiation dose.
Temperature imaging of laser-induced thermotherapy (LITT) by MRI: evaluation of different sequences in phantom

The purpose of this study was to evaluate magnetic resonance (MR) temperature imaging of the laser-induced thermotherapy (LITT) comparing the proton resonance frequency (PRF) and T 1 thermometry methods. LITT was applied to a liver-mimicking acrylamide gel phantom. Temperature rise up to 70 °C was measured using a MR-compatible fiber-optic thermometer. MR imaging was performed by a 1.5-T scanner utilizing fast gradient echo sequences including a segmented echo planar imaging (seg-EPI) sequence for PRF and the following sequences for T 1 method: fast low-angle shot (FLASH), inversion recovery turbo flash (IRTF), saturation recovery turbo flash (SRTF), and true fast imaging (TRUFI). Temperature-induced change of the pixel values in circular regions of interest, selected on images under the temperature probe tip, was recorded. For each sequence, a calibration constant could be determined to be −0.0088 ± 0.0002 ppm °C−1 (EPI), −1.15 ± 0.03 °C−1 (FLASH), −1.49 ± 0.03 °C−1 (IRTF), −1.21 ± 0.03 °C−1 (SRTF), and −2.52 ± 0.12 °C−1 (TRUFI). These constants were evaluated in further LITT experiments in phantom comparing the calculated temperatures with the fiber optic-measured ones; temperature precisions of 0.60 °C (EPI), 0.81 °C (FLASH), 1.85 °C (IRTF), 1.95 °C (SRTF), and 3.36 °C (TRUFI) were obtained. Furthermore, performing the Bland–Altman analysis, temperature accuracy was determined to be 0.23 °C (EPI), 0.31 °C (FLASH), 1.66 °C (IRTF), 1.19 °C (SRTF), and 3.20 °C (TRUFI). In conclusion, the seg-EPI sequence was found to be more convenient for MR temperature imaging of LITT due to its relatively high precision and accuracy. Among the T 1 method sequences, FLASH showed the highest accuracy and robustness.
Fludarabine and epirubicin in the treatment of chronic lymphocytic leukaemia: a German multicenter phase II study.

Fludarabine has been reported to be the most effective single-agent in previously treated chronic lymphocytic leukaemia (CLL). Based on the in vitro synergism of fludarabine with anthracyclines and on results showing a higher efficacy of CHOP against COP we attempted to improve treatment results with a combination of fludarabine and an anthracycline.



The aim of the multicenter study was to evaluate the rate and duration of remissions and investigate the toxic and immunosuppressive effects of fludarabine and epirubicin in the treatment of CLL in Binet stages B and C as first-line therapy or in first relapse. Thirty-eight patients were treated with fludarabine 25 mg/m2 on days 1-5 and epirubicin 25 mg/m2 on days 4 and 5.



The overall response rate (OR) was 82% (95% confidence interval (95% CI): 66%-92%) with a CR rate of 32% (95% CI: 18%-49%). For the 25 previously untreated patients the OR was 92% (95% CI: 74%-99%) including 40% CRs (95% CI: 21%-61%). Granulocytopenia grade 3 occurred in 23% of all evaluable cycles, and grade 4 in 17%. The median remission duration was 19 months (range 6-37 months).



The results show that the combination of fludarabine and epirubicin is tolerable and highly effective in the treatment of CLL. With the addition of epirubicin to fludarabine, it appears possible to achieve a higher response rate and a more rapid response, especially of nodal manifestations. This regimen can be administered in an outpatient facility except for the first cycle because of the risk of a tumour lysis. The possible benefit of the combination presented here in the treatment of CLL in comparison to single-agent fludarabine treatment is presently under study in a prospective randomized multicenter study.
Randomized study of the safety and clinical utility of rotational angiography versus standard angiography in the diagnosis of coronary artery disease.

This study evaluates the safety and clinical utility of rotational angiography in the diagnosis of coronary artery disease. High-speed rotational angiography is a newly available angiographic modality that gives a dynamic multiple-angle perspective of the coronary tree during a single contrast injection. We prospectively randomized 56 patients referred for diagnostic coronary angiography to either standard or rotational angiography. Contrast and radiation utilization were compared between the two groups. The number of additional cine acquisitions needed was used to determine adequacy of the diagnostic study protocol. Rotational angiography was successfully completed in all subjects. There was a 33% reduction in contrast utilization in the rotational group as compared to the standard group (35.6 +/- 12.6 vs. 52.8 +/- 10.7 ml, respectively; P < 0.0001). Additionally, there was a 28% reduction in total radiation exposure in the rotational group as compared to the standard group (39.0 +/- 18.5 vs. 53.9 +/- 23.4 Gycm(2), respectively; P = 0.01). Total whole-body radiation exposure to the primary operator was 144 mrem with rotational angiography and 170 mrem with standard angiography. Procedure time tended to be shorter for rotational angiography (353.9 +/- 146.7 vs. 396.8 +/- 165.8 s; P = 0.3). Rotational coronary angiography can be rapidly performed in any patient and provides a significant reduction in contrast and radiation utilization while at the same time providing adequate angiographic data to complement or replace standard coronary angiography in the evaluation of coronary artery disease.
The design and rationale for the Acute Medically Ill Venous Thromboembolism Prevention with Extended Duration Betrixaban (APEX) study.

Randomized clinical trials have identified a population of acute medically ill patients who remain at risk for venous thromboembolism (VTE) beyond the standard duration of therapy and hospital discharge. The aim of the APEX study is to determine whether extended administration of oral betrixaban (35-42 days) is superior to a standard short course of prophylaxis with subcutaneous enoxaparin (10 ± 4 days followed by placebo) in patients with known risk factors for post-discharge VTE. Patients initially are randomized to receive either betrixaban or enoxaparin (and matching placebo) in a double dummy design. Following a standard duration period of enoxaparin treatment (with placebo tablets) or betrixaban (with placebo injections), patients receive only betrixaban (or alternative matching placebo). Patients are considered for enrollment if they are older than 40 years, have a specified medical illness, and restricted mobility. They must also meet the APEX criteria for increased VTE risk (aged ≥75 years, baseline D-Dimer ≥2× upper the limit of "normal", or 2 additional ancillary risk factors for VTE). The primary efficacy end point is the composite of asymptomatic proximal deep venous thrombosis, symptomatic deep venous thrombosis, non-fatal (pulmonary embolus) pulmonary embolism, or VTE-related death through day 35. The primary safety outcome is the occurrence of major bleeding. We hypothesize that extended duration betrixaban VTE prophylaxis will be safe and more effective than standard short duration enoxaparin in preventing VTE in acute medically ill patients with known risk factors for post hospital discharge VTE.
The intestinal ecosystem in chronic functional constipation.

Chronic functional constipation is common in infants, and the bacterial composition of stools in this condition is not known. The study aims were to: (i) investigate the composition of the intestinal ecosystem in chronic functional constipation; (ii) establish whether the addition of the water-holding agent calcium polycarbophil to the diet induces an improvement in constipation; and (iii) determine the composition of the intestinal ecosystem after the use of this agent. In total, 42 children (20F, 22M; mean age: 8.6 +/- 2.9 y) were studied. Twenty-eight children with functional chronic constipation without anatomical disorders were treated double-blind in random sequence for 1 month with an oral preparation of calcium polycarbophil (0.62 g/twice daily) or placebo. Intestinal flora composition was evaluated by standard microbiological methods and biochemical assays on faecal samples collected before and after treatment. Fourteen healthy children were studied as controls. The results show that (i) the constipated children presented a significant increase in clostridia and bifidobacteria in faeces compared to healthy subjects--different species of clostridia and enterobacteriaceae were frequently isolated; no generalized overgrowth was observed; Clostridia outnumbered bacteroides and E. coli mean counts by 2-3log, while bacteroides and E. coli counts were similar (5-6 log10/g fresh faeces); these intestinal disturbances could be defined as a dysbiosis, i.e. a quantitative alteration in the relative proportions of certain intestinal bacterial species. (ii) Clinical resolution of constipation was achieved only in 43% of treated children and an improvement in 21% (one bowel movement every 2 d). (iii) Calcium polycarbophil treatment induced no significant changes in the composition of the intestinal ecosystem, nor in blood chemistry parameters.
T cell-depleted bone marrow transplantation and delayed T cell add-back to control acute GVHD and conserve a graft-versus-leukemia effect

Thirty-eight patients with hematological malignancies, received T cell-depleted marrow transplants (BMT) and cyclosporine to prevent acute graft-versus-host disease (aGVHD), followed by delayed add-back of donor lymphocytes to prevent leukemia relapse. In 26 patients scheduled for donor T cell add-back of 2 × 106 cells/kg on day 30 and 5 × 107 cells/kg on day 45 (schedule 1), the overall probability of grade ⩾II aGVHD developing was 31.5%, with a 15.5% probability of aGVHD occurring after T cell add-back. In 12 patients receiving 107 donor T cells/kg on day 30 (schedule 2), the probability of grade ⩾II aGVHD was 100%. The incidence of grade III–IV aGVHD was higher in schedule 2 than in schedule 1 (P = 0.02). Of 24 evaluable patients, 10 (46%) developed chronic GVHD which was limited in eight and extensive in two. Current disease-free survival for 18 patients at standard risk for relapse (chronic myeloid leukemia (CML) in chronic or accelerated phase, acute myeloid leukemia in remission) vs 20 patients with more advanced leukemia or multiple myeloma were respectively 72% vs 12% (P < 0.01) with a 29% vs 69% probability of relapse (P = 0.08). In 12 CML patients surviving more than 3 months, PCR analysis of the BCR/ABL transcript showed that minimal residual disease after T cell add-back was transient except in two patients who developed hematological relapse. Results indicate that the risk of acute GVHD is low following substantial T cell doses, transfused 45 days after transplant, using cyclosporine prophylaxis. Furthermore a graft-versus-leukemia effect was conserved.
The diagnostic capacity of forced oscillation and forced expiration techniques in identifying asthma by isocapnic hyperpnoea of cold air.

The measurement of forced expiratory volume in one second (FEV1) is often used to assess the effect of bronchial provocations, and deep inspiration is required beforehand. This may briefly alter the bronchial tone in a variable way in some subjects. The forced oscillation technique (FOT) is a test used to characterize the mechanical impedance of the respiratory system, and prior deep inspiration is not required. We tested the hypothesis that measurable bronchoconstriction would occur in all asthmatic subjects stimulated with isocapnic hyperventilation of dry cold air (IHCA). Twenty patients with mild asthma and nine healthy controls were exposed to IHCA, at 70% of their maximal voluntary ventilatory capacity for 4 min and the results were assessed both by applying the FOT and by measuring FEV1. Optimal cut-off levels were defined by receiver operating characteristic (ROC) curve analyses of the changes in respiratory resistance and reactance at 5-35 Hz, resonant frequency (fres) and FEV1. A positive result was present in the asthmatics when measured by FOT, and using ROC analyses the discriminative capacity to correctly diagnose asthma was greatest for responses in fres; the sensitivity was 89% and the specificity 100%. The sensitivity of FEV1 to correctly diagnose asthma was only 73%, and the specificity 88%. In conclusion, the results of this study suggest that the use of forced expiratory volume in one second for bronchial provocation tests by isocapnic hyperventilation of dry cold air may be misleading and that the bronchoconstriction thus elicited is measured with greater sensitivity and specificity by the forced oscillation technique than by forced expiratory volume in one second.
6DMPP: small worlds in mobile peer-to-peer networks

We present 6DMPP, a novel network routing protocol that improve routing performance by applying the small word concept to reducing average routing lengths. The key idea is to arrange all nodes along a logic circle and equip them with long distance links drawn from a family of power law distribution. We also introduce deceasing failure detection and failure repairs techniques to maintain long distance links at a small cost. Through simulations, we demonstrate that our approach performs comparably, or better than, the existing wireless routing protocol.
Parameter identification for a local field potential driven model of the Parkinsonian subthalamic nucleus spike activity

Several models, with various degrees of complexity have been proposed to model the neuronal activity from different parts of the human brain. We have shown before that various modeling approaches, including a Hammerstein-Wiener (H-W) model, can be used to predict the spike trains from a deep nucleus, the subthalamic nucleus, using the underlying local field potentials. In this article, we present, in depth, the various choices one has to make, and the limitations that they introduce, during the H-W model parameter identification process. From a segment of the recorded data, which contains information about the spike times of a single neuron, we identify and extract the model parameters. We then use those parameters to numerically simulate the spike timing, the rhythm and the inter-spike intervals for the rest of the recording. To assess how well the model fits to the measured data we combine measures of spike train synchrony, namely the Victor-Purpura distance and the Gaussian similarity measure, with time-scale independent train distances. We show that a wise combination of metrics results in models that predict the spikes with temporal accuracy ranging, on average, from 53% to more than 80%, depending on the number of the neurons' spikes recorded. The model's prediction is adequate for estimating accurately the spike rhythm. Quantitative results establish the model's validity as a simple yet biologically plausible model of the spike activity recorded from a deep nucleus inside the human brain.
Effects of indomethacin prophylaxis timing on intraventricular haemorrhage and patent ductus arteriosus in extremely low birth weight infants.

Indomethacin prophylaxis (IP) reduces the risk of intraventricular haemorrhage (IVH) and patent ductus arteriosus (PDA) in preterm infants. However, the optimal time to administer IP has not been determined. We hypothesised that IP at ≤6 h is associated with a lower incidence of IVH or death than if administered at >6-24 h of age.



We performed a retrospective cohort study of extremely low birth weight infants (≤1000 g birth weight) treated in the neonatal intensive care units in the Neonatal Research Network from 2003 to 2010 and who received IP in the first 24 h of age. Infants were dichotomised based upon receipt of IP at ≤6 or >6-24 h of age. The primary outcomes were IVH alone and IVH or death. Secondary outcomes were PDA alone and PDA or death. We used multivariable analyses to determine associations between the age of IP and the study outcomes expressed as an OR and 95% CI.



IP was given at ≤6 h to 2340 infants and at >6-24 h to 1915 infants. Infants given IP at ≤6 h had more antenatal steroid exposure, more inborn and less cardiopulmonary resuscitation (p<0.01). After multivariable analyses, age of IP receipt was not associated with IVH, and IVH or death but PDA receiving treatment/ligation or death was lower among IP at ≤6 h compared with IP at >6-24 h (OR 0.83, 95% CI 0.71 to 0.98).



IP at ≤6 h of age is not associated with less IVH or death, but is associated with less PDA receiving treatment/ligation or death.
Behavioral drug and HIV risk reduction counseling (BDRC) with abstinence-contingent take-home buprenorphine: a pilot randomized clinical trial.

This pilot randomized clinical trial evaluated whether the efficacy of office-based buprenorphine maintenance treatment (BMT), provided with limited counseling or oversight of medication adherence is improved by the addition of individual drug counseling and abstinence-contingent take-home doses of buprenorphine. After a 2-week buprenorphine and stabilization period, heroin dependent individuals (n=24) in Muar, Malaysia were randomly assigned to Standard Services BMT (physician administered advice and support, and weekly, non-contingent medication pick-up) or Enhanced Services (nurse-delivered manual-guided behavioral drug and HIV risk reduction counseling (BDRC) and abstinence-contingent take-home buprenorphine (ACB), 7 day supply maximum). Outcomes included retention, proportion of opioid-negative urine tests, self-reported drug use, and self-reported HIV risk behaviors. 12/12 (100%) of Enhanced Services and 11/12 (92%) of Standard Services participants completed the entire protocol. The proportion of opioid-negative urine tests increased significantly over time for both groups (p<0.001), and the reductions were significantly greater in the Enhanced Services group (p<0.05); Enhanced Services group achieved higher overall proportions of opiate negative urine toxicology tests (87% vs. 69%, p=0.04) and longer periods of consecutive abstinence from opiates (10.3 weeks vs. 7.8 weeks, p=0.154). Both groups significantly reduced HIV risk behaviors during treatment (p<0.05), but the difference between Enhanced and Standard Services (26% vs. 17% reductions from the baseline levels, respectively) was not statistically significant (p=0.9). Manual-guided behavioral drug and HIV risk reduction counseling and abstinence-contingent take-home buprenorphine appear promising for adding to the efficacy of office-based BMT provided with limited drug counseling and medication oversight.