Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase I study of RO4929097, a gamma secretase inhibitor of Notch signaling, in patients with refractory metastatic or locally advanced solid tumors.

PURPOSE To determine the maximum-tolerated dose (MTD) and assess safety, pharmacokinetics, pharmacodynamics, and evidence of antitumor activity of RO4929097, a gamma secretase inhibitor of Notch signaling in patients with advanced solid malignancies. PATIENTS AND METHODS Patients received escalating doses of RO4929097 orally on two schedules: (A) 3 consecutive days per week for 2 weeks every 3 weeks; (B) 7 consecutive days every 3 weeks. To assess reversible CYP3A4 autoinduction, the expanded part of the study tested three dosing schedules: (B) as above; modified A, 3 consecutive d/wk for 3 weeks; and (C) continuous daily dosing. Positron emission tomography scans with [(18)F]fluorodeoxyglucose (FDG-PET) were used to assess tumor metabolic effects. RESULTS Patients on schedule A (n = 58), B (n = 47), and C (n = 5; expanded cohort) received 302 cycles of RO4929097. Common grade 1 to 2 toxicities were fatigue, thrombocytopenia, fever, rash, chills, and anorexia. Transient grade 3 hypophosphatemia (dose-limiting toxicity, one patient) and grade 3 pruritus (two patients) were observed at 27 mg and 60 mg, respectively; transient grade 3 asthenia was observed on schedule A at 80 mg (one patient). Tumor responses included one partial response in a patient with colorectal adenocarcinoma with neuroendocrine features, one mixed response (stable disease) in a patient with sarcoma, and one nearly complete FDG-PET response in a patient with melanoma. Effect on CYP3A4 induction was observed. CONCLUSION RO4929097 was well tolerated at 270 mg on schedule A and at 135 mg on schedule B; the safety of schedule C has not been fully evaluated. Further studies are warranted on the basis of a favorable safety profile and preliminary evidence of clinical antitumor activity.
Variation of second cancer risk by family history of retinoblastoma among long-term survivors.

PURPOSE To evaluate the risk of second cancer (SC) in long-term survivors of retinoblastoma (Rb) according to classification of germline mutation, based on family history of Rb and laterality. PATIENTS AND METHODS We assembled a cohort of 1,852 1-year survivors of Rb (bilateral, n = 1,036; unilateral, n = 816). SCs were ascertained by medical records and self-reports and confirmed by pathology reports. Classification of RB1 germline mutation, inherited or de novo, was inferred by laterality of Rb and positive family history of Rb. Standardized incidence ratios and cumulative incidence for all SCs combined and for soft tissue sarcomas, bone cancers, and melanoma were calculated. The influence of host- and therapy-related risk factors for SC was assessed by Poisson regression for bilateral survivors. RESULTS We observed a relative risk (RR) of 1.37 (95% CI, 1.00 to 1.86) for SCs in bilateral survivors associated with a family history of Rb, adjusted for treatment, age, and length of follow-up. The risk for melanoma was significantly elevated for survivors with a family history of Rb (RR, 3.08; 95% CI, 1.23 to 7.16), but risks for bone or soft tissue sarcomas were not elevated. The cumulative incidence of SCs 50 years after diagnosis of bilateral Rb, with adjustment for competing risk of death, was significantly higher for survivors with a family history (47%; 95% CI, 35% to 59%) than survivors without a family history (38%; 95% CI, 32% to 44%; P = .004). CONCLUSION Rb survivors with bilateral disease and an inherited germline mutation are at slightly higher risk of an SC compared with those with a de novo germline mutation, in particular melanoma, perhaps because of shared genetic alterations.
Class-D CMOS Oscillators

This paper presents class-D CMOS oscillators capable of an excellent phase noise performance from a very low power supply voltage. Starting from the recognition of the time-variant nature of the class-D LC tank, accurate expressions of the oscillation frequency, oscillation amplitude, current consumption, phase noise, and figure-of-merit (FoM) have been derived. Compared with the commonly used class-B/C architectures, the optimal class-D oscillator produces less phase noise for the same power consumption, at the expense of a higher power supply pushing. A prototype of a class-D voltage-controlled oscillator (VCO) targeted for mobile applications, implemented in a standard 65-nm CMOS process, covers a 46% tuning range between 3.0 and 4.8 GHz; drawing 10 mA from 0.4 V, the phase noise at 10-MHz offset from 4.8 GHz is -143.5 dBc/Hz, for an FoM of 191 dBc/Hz with less than 1-dB variation across the tuning range. A version of the same VCO with a resonant tail filter displays a lower 1/f3 phase-noise corner and improves the FoM by 1 dB.
SAW-less analog front-end receivers for TDD and FDD

In cellular receivers, out-of-band blockers are generally managed by surface-acoustic-wave (SAW) filters between the antenna and the low-noise amplifier (LNA). For Time Division Duplexing (TDD), such as GSM, the SAW can be removed if the receiver can handle very large interferers (e.g. in GSM 0dBm 20 MHz away) [1]. Generally SAW filters also perform differential to single-ended (SE) conversion (balun). Once the SAW is removed an SE transceiver eliminates the external balun, reducing cost and attenuation. For the same sensitivity, a SAW-less SE transceiver can have a noise figure (NF) 2 to 3dB higher than a classical one. An SE LNA could be susceptable to couplings from supply and substrate, which are usually rejected through symmetry. Therefore it should become symmetric as closely as possible to the input pin. A SAW-less differential transceiver [2] can also be appealing if it has an NF close to that of classical transceivers. This is because it can have better sensitivity in TDD (a balun attenuates less than a SAW) and it can be very flexible, being usable for both FDD (where duplexers are differential) and TDD.
Clinicopathologic characteristics of angioimmunoblastic T-cell lymphoma: analysis of the international peripheral T-cell lymphoma project.

PURPOSE The International Peripheral T-Cell Lymphoma Project was undertaken to better understand the subtypes of T-cell and natural killer (NK) -cell lymphomas. PATIENTS AND METHODS Angioimmunoblastic T-cell lymphoma (AITL) was diagnosed according to the 2001 WHO criteria by a central review process consisting of panels of expert hematopathologists. Clinical, pathologic, immunophenotyping, treatment, and survival data were correlated. RESULTS Of 1,314 patients, 243 (18.5%) were diagnosed with AITL. At presentation, generalized lymphadenopathy was noted in 76% of patients, and 89% had stages III to IV disease. Skin rash was observed in 21% of patients. Hemolytic anemia and hypergammoglobulinemia occurred in 13% and 30% of patients, respectively. Five-year overall and failure-free survivals were 33% and 18%, respectively. At presentation, prognostic models were evaluated, including the standard International Prognostic Index, which comprised the following factors: age ≥ 60 years, stages III to IV disease, lactic dehydrogenase (LDH) > normal, extranodal sites (ENSs) > one, and performance status (PS) ≥ 2; the Prognostic Index for Peripheral T-Cell Lymphoma, comprising: age ≥ 60 years, PS ≥ 2, LDH > normal, and bone marrow involvement; and the alternative Prognostic Index for AITL (PIAI), comprising: age > 60 years, PS ≥ 2, ENSs > one, B symptoms, and platelet count < 150 × 10(9)/L. The simplified PIAI had a low-risk group (zero to one factors), with 5-year survival of 44%, and a high-risk group (two to five factors), with 5-year survival of 24% (P = .0065). CONCLUSION AITL is a rare clinicopathologic entity characterized by an aggressive course and dismal outcome with current therapies.
Muscle microvascular adaptation and angiogenic gene induction in response to exercise training are attenuated in middle-aged rats

This study was designed to investigate exercise-induced changes in muscle capillarisation, the mRNA expression of angiogenic genes, and microRNA levels in young and middle-aged rats. Rats in the training groups were subjected to treadmill running 5 days a week for 3 weeks. The exercise protocol for the young (12-week old) group was 20-25 m/min, 40-60 min/day with a gradient of 15%, and for the middle-aged (12-month old) group was 18-20 m/min, 40-60 min/day with a gradient of 5%. The enzyme histochemical identification of capillary profiles was performed on cross-sections of gastrocnemius muscle. Total RNA was isolated, reverse transcription was performed, and mRNA and microRNA levels were determined by real-time PCR. The capillary-to-fibre ratio was significantly increased by exercise training in the young group (by 10%), but only slightly in the middle-aged (by 5%) group. Vascular endothecial growth factor (VEGF) mRNA levels were at significantly higher values after acute exercise (1.6-fold) and the 3-we.
Extradural Corticosteroid Injection in Management of Lumbar Nerve Root Compression

The effect of extradural corticosteroid injection in patients with nerve root compression syndromes associated with degenerative disease of the lumbar intervertebral discs was assessed in a double-blind controlled trial on 100 consecutive inpatients assigned by random allocation to treatment and control groups. Assessment during admission and at three months revealed statistically highly significant differences in respect of relief of pain and resumption of normal occupation in favour of the group treated by extradural injection. This treatment seems to be a valuable adjunct to the management of lumbar nerve root compression syndromes associated with degenerative disc disease.
Fully Integrated Frequency Reference With 1.7 ppm Temperature Accuracy Within 0–80°C

A fully integrated 52 MHz frequency reference, designed in a 0.35 μm CMOS process, achieves 1.7 ppm frequency temperature accuracy within 0 to 80°C using a nonlinear compensation technique. The proposed low TCf0 reference oscillator achieves the lowest reported uncompensated temperature coefficient, i.e., 65.25 ppm/°C, among the integrated frequency references. The output reference frequency is obtained by dividing the differential LC Colpitts oscillator output operating at 1.6 GHz. Oscillator core dissipates 14 mW from 2.5 V. The blocks related to the temperature compensation scheme and the remaining system blocks consume 3 mW and 165 mW from 3.3 V supply, respectively. The measured phase noise of 52 MHz output is -94 dBc/Hz at 10 kHz offset frequency and rms period jitter is 3.2 ps.
Short, full-dose adjuvant chemotherapy in high-risk adult soft tissue sarcomas: a randomized clinical trial from the Italian Sarcoma Group and the Spanish Sarcoma Group.

PURPOSE A previous randomized clinical trial by the Italian Sarcoma Group (ISG) had shown a survival benefit of adjuvant chemotherapy (CT) in high-risk extremity soft tissue sarcoma (STS). However, the dose-intensity of the last two cycles was suboptimal. We then undertook a multicentric international phase III study to compare three and five cycles of the same CT. PATIENTS AND METHODS Patients were randomly assigned either to receive three cycles of preoperative CT with epirubicin 120 mg/m(2) and ifosfamide 9 g/m(2) and granulocyte colony-stimulating factor (arm A) or to receive the same three cycles of preoperative CT followed by two further cycles of postoperative CT (arm B). Noninferiority of the primary end point, overall survival (OS), was assessed by the CI of the hazard ratio (HR; arm A/arm B) obtained from the Cox model. RESULTS Between January 2002 and April 2007, 328 patients were recruited (164 patients in each arm). At a median follow-up of 63 months (interquartile range, 49 to 77 months), 100 deaths were recorded, 49 in arm A and 51 in arm B. Five-year OS probability was 0.70 for the entire group of patients (0.68 in arm A and 0.71 in arm B). The HR of arm A versus arm B was 1.00 (90% CI, 0.72 to 1.39). CONCLUSION In this population of patients with high-risk localized STS, three cycles of full-dose preoperative CT were not inferior to five cycles. The outcome compares favorably with the expected survival of patients with high-risk STS and was superimposable on the CT arm of the previous ISG trial.
A 1 TOPS/W Analog Deep Machine-Learning Engine With Floating-Gate Storage in 0.13 µm CMOS

An analog implementation of a deep machine-learning system for efficient feature extraction is presented in this work. It features online unsupervised trainability and non-volatile floating-gate analog storage. It utilizes a massively parallel reconfigurable current-mode analog architecture to realize efficient computation, and leverages algorithm-level feedback to provide robustness to circuit imperfections in analog signal processing. A 3-layer, 7-node analog deep machine-learning engine was fabricated in a 0.13 μm standard CMOS process, occupying 0.36 mm 2 active area. At a processing speed of 8300 input vectors per second, it consumes 11.4 μW from the 3 V supply, achieving 1×10 12 operation per second per Watt of peak energy efficiency. Measurement demonstrates real-time cluster analysis, and feature extraction for pattern recognition with 8-fold dimension reduction with an accuracy comparable to the floating-point software simulation baseline.
A 6 bit 10 GS/s TI-SAR ADC With Low-Overhead Embedded FFE/DFE Equalization for Wireline Receiver Applications

High-speed ADC front-ends in wireline receivers allow for implementing flexible, complex, and robust equalization in the digital domain, as well as easily supporting bandwidth-efficient modulation schemes, such as PAM4 and duobinary. However, the power consumption of these ADC front-ends and subsequent digital signal processing is a major issue. This paper presents a 64-way 6 bit 10 GS/s time-interleaved successive-approximation-based ADC front-end that efficiently incorporates a two-tap embedded FFE and a one-tap embedded DFE, providing the potential for a lower complexity back-end DSP and/or decreased ADC resolution. Fabricated in a 1.1V GP 65nm CMOS process, the ADC with embedded equalization achieves 0.48 pJ/conv. -step FOM, while consuming 79.1mW and occupying 0.33 mm2 core ADC area. The effectiveness of the embedded FFE and DFE is demonstrated with significant timing margin improvement observed for 10 Gb/s operation over several FR4 channels.
A 28 nm FDSOI Integrated Reconfigurable Switched-Capacitor Based Step-Up DC-DC Converter With 88% Peak Efficiency

This paper presents a fully integrated, reconfigurable switched-capacitor based step-up DC-DC converter in a 28 nm FDSOI process. Three reconfigurable step-up conversion ratios (5/2, 2/1, 3/2) have been implemented which can provide a wide range of output voltage from 1.2 V to 2.4 V with a nominal input voltage of 1 V. We propose a topology for the 5/2 mode which improves the efficiency by reducing the bottom-plate parasitic loss compared to a conventional series-parallel topology, while delivering the same amount of output power. Further, the proposed topology benefits from using core 1 V devices for all charge-transfer switches without incurring any voltage overstress. The converter can deliver load current in the range of 10 μA to 500 μA, achieving a peak efficiency of 88%, using only on-chip MOS and MOM capacitors for a high density implementation.
Estimation of Water Content in Sour Gases

Abstract Estimating the water content of natural gases is necessary in many chemical and petroleum engineering processes, e.g., calculating the amount of water condensed in a pipeline for designing hydrate inhibition strategy. An empirical method based on correction of ideal model for estimating the water content of sweet natural gases in equilibrium with the liquid water or ice has been developed. This predictive method estimates the water content of sweet natural gases using the water/ice vapor pressure, the system pressure and temperature. In order to extend the capabilities of the new approach to sour gases, a correction factor is proposed for taking into account the effect of acid gases on the water content. The new approach has been developed using the predictions of a comprehensive thermodynamic model as pseudo experimental data. The data on water content of methane with different concentrations of carbon dioxide and hydrogen sulfide were generated and fed to a multi-dimension regression program. The predictions of the developed empirical correlations are in good agreement with independent experimental data, demonstrating their reliability in estimating the water content of natural gases. Finally, a discussion is made on determining the location of water condensation along a pipeline using a simplified energy balance equation and the method developed in this work.
Economic and public health impact of 2007–2010 tobacco tax increases in Ukraine

Objective To evaluate the impact of the dynamic 2007–2010 tobacco tax policy in Ukraine on cigarette prices, cigarette consumption, tobacco tax revenue and the tobacco industry's price strategy. Methods Using data on cigarette sales, cigarette prices, income and tobacco control policies, price elasticities of cigarette demand in Ukraine were estimated using two methods. Annual data were used to generate point price elasticity estimates, while monthly data were used in a two-step Engle–Granger procedure. Results The point price elasticity estimate is data sensitive and ranges from −0.11 to −0.62, centring around −0.32. The regression model estimates a long-run price elasticity of −0.28. Cigarette consumption fell by 13% in 2009 and 15% in 2010 while the tax revenue increased by US$700 million and by US$500 million in 2009 and 2010, respectively, compared to the previous year. Tax increases have changed the tobacco industry's price strategy from one of shielding consumers from the impact of smaller tax hikes in 2007–2008, to one of increasing industry net-of-tax prices, after recent, larger tax increases. Conclusions The higher real tobacco excise taxes of 2009 and 2010 have significantly reduced tobacco consumption in Ukraine, resulting in encouraging public health and fiscal gains. It will be important for cigarette prices/taxes to keep pace with inflation and income growth for this impact to be sustained.
Early-stage hodgkin's lymphoma: in pursuit of perfection.

It was estimated that 8,830 patients would be diagnosed with Hodgkin’s lymphoma (HL) in the United States in 2011, and that approximately half of those patients would have early-stage disease. The treatmentofearly-stageHLhasevolvedovertime,resultingincontinuous improvement in the cure rate and reductions in treatment-related toxicity. Today, combined modality programs are considered the standard of care for the majority of these patients, with an expected cure rate exceeding 80% and survival rate exceeding 90%. Despite these outstanding results, several groups continue to develop treatment programs in the hopes of achieving better curative and safety outcomes. To understand the results of key randomized studies in patients with early-stage HL, it is important to remember that the definition of early-stage disease varies widely among study groups and in different regions of the world. In North America, early stage is defined as stage I or II disease with no bulk or B symptoms. Patients with such disease are typically treated with four cycles of doxorubicin, bleomycin, dacarbazine, and vinblastine (ABVD) plus 30 Gy of involved field radiation therapy (IF-XRT). In contrast, patients with bulky disease ( 10 cm) are usually grouped with patients with advanced-stage disease and are treated with six to eight cycles of ABVD plus 36 Gy of IF-XRT, resulting in a 5-year failure-free survival of 85% and an overall survival of 95%. The definition of early stage that is used by the German Hodgkin’s Lymphoma Study Group (GHLSG) includes bulky stage I or II disease with no B symptoms. The GHLSG additionally classifies patients with early-stage disease into favorable (stage I/II disease with no risk factors such as bulk, elevated erythrocyte sedimentation rate, extranodal sites, or more than two involved lymph node regions) or unfavorable (stage I/II with any of these risk factors) categories. Patients with early-stage favorable HL have an excellent cure rate; therefore, investigations of new therapeutic programs focus on reducing treatment-related toxicity, whereas patients with early-stage unfavorable HL continue to be candidates for the evaluation of new regimens that are aimed at additionally improving the cure rate. Using this approach, the GHLSG reported that patients with early-stage favorable HL could be successfully treated with a reduced-intensity regimen of two cycles of ABVD chemotherapy plus 20 Gy of IF-XRT instead of the standard four cycles of ABVD plus 30 Gy of IF-XRT. Using such a strategy, they were able to maintain a high 91% rate of freedom from treatment failure. In the article that accompanies this editorial, the GHLSG reports the results of the HD14 study that was aimed at improving treatment outcomes of patients with early-stage unfavorable HL by intensifying
Randomized trial of myeloablative conditioning regimens: busulfan plus cyclophosphamide versus busulfan plus fludarabine.

PURPOSE We conducted a phase III randomized clinical trial to compare two myeloablative conditioning regimens for allogeneic hematopoietic cell transplantation (HCT) in patients with leukemia and myelodysplastic syndrome. PATIENTS AND METHODS After randomization, 64 patients received busulfan (3.2 mg/kg per day × 4 days) plus cyclophosphamide (60 mg/kg per day × 2 days; BuCy), and 62 patients received busulfan (same dose and schedule) plus fludarabine (30 mg/m(2) per day × 5 days; BuFlu). RESULTS The median age was 41 years (range, 17 to 59 years). Five patients in the BuFlu arm experienced graft failure (primary, n = 1; secondary, n = 4). At 4 weeks after HCT, the median percentage of recipient hematopoietic chimerism was significantly greater in the BuFlu arm (0% v 5.5%; P < .001), and complete donor chimerism was greater in the BuCy arm (97.2% v 44.4%; P < .001). Severe (grade 3 or higher) infection and gastrointestinal adverse events were significantly more common in the BuCy arm, but the frequencies of hepatic adverse events were similar in the two arms. Nonrelapse mortality was similar in the two arms, but the BuCy arm had better overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS; OS at 2 years, 67.4% v 41.4%, P = .014; RFS, 74.7% v 54.9%, P = .027; EFS, 60.7% v 36.0%, P = .014). CONCLUSION Our results indicate that the BuFlu regimen is not a suitable replacement for the BuCy regimen in young adults who are eligible for myeloablative conditioning therapy for allogeneic HCT.
Nutrition and Cost Comparisons of Select Canned, Frozen, and Fresh Fruits and Vegetables

A common call to action for addressing public health concerns of both obesity and hunger is improving access to and consumption of fruits and vegetables. Previous research has examined the nutritional merits of fresh, frozen, and canned fruits and vegetables. However, there are limited data on the cost-effectiveness of fresh compared with processed—that is, canned and frozen—food. This study examined the nutrition delivered in 8 common vegetables and 10 common fruits across multiple packaging options (fresh, frozen, and canned) relative to average costs. A method of scoring based on nutrient intake recommendations was used to calculate the nutrients per calorie, and average costs were obtained from the US Department of Agriculture’s Economic Research Service. Nutrient scores for the vegetables were similar across the 3 packaging options, whereas canned vegetables had a lower cost per edible cup compared with frozen and fresh. Nutrient scores were variable for the fruits across the 3 packaging options, and canned fruits were either lower or comparably priced per edible cup. The evidence from this study suggests that fruits and vegetables packaged as frozen or canned are cost-effective and nutritious options for meeting daily vegetable and fruit recommendations in the context of a healthy diet.