Miracle-dz/UniFAR-FTUs huggingface dataset:
A safety and schedule seeking trial of Bcl-2 inhibitor obatoclax in previously untreated older patients with acute myeloid leukemia (AML).

3579 Background: Obatoclax (Ob) is a small-molecule inhibitor of all Bcl-2 prosurvival proteins. In a previous study a 70 year old patient with untreated AML had a cytogenetic CR 8 days after receiving 20 mg/m2 of Ob over 24 hrs. This study evaluated the single-agent response rate in older patients with previously untreated AML. METHODS A Safety phase to evaluate escalating doses of Ob given by 3-hr infusion was performed. Based on previous results, the dose of 60 mg over 24 hrs was used for the 24-hr infusion arm of the Schedule Seeking phase, in which Ob was administered as either a 3-hr or 24-hr infusion for 3 consecutive days every 2 wks. The endpoint of the Schedule Seeking phase was CR after C2 in 16 randomized patients. Eligibility criteria included age ≥ 70, untreated AML (1 prior Rx allowed in Safety phase), ECOG PS ≤2, adequate renal and hepatic function. PK samples were collected during C1. RESULTS 18 patients (8 male; median age 82) were enrolled. 2/3 patients enrolled into the 1st cohort (30 mg x 3 days) of the Safety phase had DLT events (ataxia and somnolence). 3 patients enrolled into a 20 mg x 3 days cohort had no DLTs; this dose was used for Schedule Seeking patients receiving 3-hr infusions. In the Schedule Seeking phase, 7 patients were randomized to receive 20 mg by 3-hr infusion and 5 were randomized to receive 60 mg by 24-hr infusion. The most common (>25%) AEs were euphoric mood (50%), ataxia (38%), & somnolence (38%). Efficacy data after C2 show that 3 patients in the 20 mg 3-hr infusion cohort in the Safety phase and 1 at the same dose & schedule in the Schedule Seeking phase had ≥50% decrease in BM blasts after C2, which was not seen in the 60 mg 24-hr infusion cohort. There were no CRs. There was a single death by D28 (24-hr infusion). There were significant differences in PK by infusion schedule. CONCLUSIONS MTD for Ob as a 3-hr infusion administered in older patients with AML on 3 consecutive days is 20 mg/day, and both this regimen and 60 mg as a 24-hr infusion x 3 days were well tolerated. Evidence of biological activity was seen with the 3-hr infusion schedule but not with the 24-hr infusion schedule, suggesting that efficacy may be improved with the 3-hr infusion schedule and may be related to PK differences. [Table: see text].
The Integration of Harm Reduction into Abstinence-based Therapeutic Communities: A Case Study of We Help Ourselves

Traditionally, therapeutic communities (TCs) have focused on providing abstinence-based treatment. However, with the emergence of HIV among injecting drug users, some TCs have evolved to include risk management or harm reduction strategies into their previously abstinence-based programs. We Help Ourselves (WHOS), a group of TCs in Australia, integrated harm reduction into their services in the 1980s. WHOS passed through a series of stages as it moved from a goal of “abstinence only” to one of “abstinence eventually. ” Following these changes, client retention and length of stay increased and HIV risk behaviors decreased. The process by which WHOS integrated harm reduction into their services while maintaining a commitment to abstinence is outlined and a guide for TCs interested in adopting harm reduction is provided.
Open-World Planning for Story Generation

The ability to generate narrative is of importance to computer systems that wish to use story effectively for entertainment, training, or education. One way to generate narrative is to use planning. However, story planners are limited by the fact that they can only operate on the story world provided, which impacts the ability of the planner to find a solution story plan and the quality and structure of the story plan if one is found. We present a planning algorithm for story generation that can nondeterministically make decisions about the description of the initial story world state in a least-commitment fashion.
Effects of pueraria root ( pueraria radix ) on the content of collagen and elastin in pelvic floor dysfunction patients

This study was performed to investigate the effects of Pueraria radix, the root of a legume Pueraria lobata (Wild.), on the content of collagen and elastin and discuss its role in treating patients with pelvic floor dysfunction (PFD). This prospective, multi-center, and randomized study was performed on postmenopausal women diagnosed with PFD planning to undergo vaginal hysterectomy. Included patients were randomly assigned into pueraria-treated group or control group. Then randomization was stratified by the Pelvic Organ Prolapse (POP) stage [early POP stage (I, II) vs advanced POP stage (III, IV)]. The primary outcome was the morphology and content of collagen and elastin, which was detected by hematoxylin-eosin (HE) and Weigert’s staining, or immunohistochemistry. The intraoperative outcome, postoperative complication and pathologic changes of endometrium and serum estradiol level were also recorded. Totally 60 patients were included, with 30 women in each group. For each group, there were 15 patients with PFD at early POP stage and 15 patients at advanced POP stage. Preoperative administration of pueraria tablet could improve the morphology and significantly increase the content of type I/III collagen and elastin (P < 0.001). Additionally, patients in pueraria-treated group had significantly shorter duration of operation (P = 0.001), less blood Loss during operation (P < 0.001). Furthermore, pueraria tablet treatment is safe and well-tolerated, with comparable adverse effects in the control group. In conclusions, preoperative administration of Pueraria radix could remarkably increase the content of collagen and elastin, which might be beneficial for postmenopausal women with PFD.
The relationship between previous treatment for cervical dysplasia and preterm delivery in twin gestations

Abstract Objective: To describe the impact of previous cervical surgery on preterm birth prior to 34 weeks in twins. Methods: A retrospective review of twin pregnancies delivered between January 1998 and December 2005 at two institutions was performed. Women with a prior cold knife cone (CKC), loop electrosurgical excision procedure (LEEP), or ablative procedure were compared to a control group of women who had not undergone a previous treatment for cervical dysplasia. The primary outcome was delivery before 34 weeks of gestation. Results: A total of 876 women met inclusion criteria. Of these, 110 (12.6%) had previous surgical procedures for cervical dysplasia, including CKC (n = 10), LEEP (n = 36), cryotherapy (n = 59) and CO2 laser treatment (n = 5). Delivery prior to 34 weeks was more common in women with a previous CKC compared to women with no prior treatment (40% versus 11.3%; odds ratio [OR], 3.6; 95% confidence interval [CI], 1.7–8.0). Delivery prior to 34 weeks was not more common in women with a previous LEEP (8.3%; OR, 0.8; 95% CI, 0.3–2.3) or ablative procedure (9.4%; OR, 0.9; 95% CI, 0.4–1.9) in comparison to the untreated group. Adjusting for the potential confounders of age, tobacco use, infertility treatments and previous preterm birth did not change the results. Conclusions: Previous CKC is associated with delivery prior to 34 weeks while LEEP and ablative procedures are not. CKC should be carefully considered and avoided when possible in reproductive age women.
Welding process impact on residual stress and distortion

Residual stress and distortion continue to be important issues in shipbuilding and are still subject to large amounts of research. This paper demonstrates how the type of welding process influences the amount of distortion. Many shipyards currently use submerged arc welding (SAW) as their welding process of choice. In this manuscript, the authors compare welds made by SAW with DC gas metal arc welding, pulsed gas metal arc welding, Fronius cold metal transfer (CMT), autogenous laser and laser hybrid welding on butt welds in 4 mm thick DH36 ship plate. Laser and laser hybrid welding were found to produce the lowest distortion. Nevertheless, a considerable improvement can be achieved with the pulsed gas metal arc welding and CMT processes. The paper seeks to understand the relationship between heat input, fusion area, measured distortion and the residual stress predicted from a simple numerical model, and the residual stresses validated with experimental data.
Gas–Liquid–Solid Operation of a Vortex-Ingesting Stirred Tank Reactor

The vortex-ingesting stirred tank reactor uses a combination of a helical screw impeller and concentric draft-tube to entrain and recycle headspace gas and disperse it as bubbles in a liquid reaction solvent. This study presents an experimental characterization of a 0.29 m diameter vortex-ingesting gas–liquid stirred reactor, operated with solid mass fractions from 0 to 25%, over a range of specific power inputs up to 3 W kg –1 and for a variety of tank geometries. As was found in previous studies, the most important geometric variable is the draft-tube top clearance, since this has the most direct effect on the gas ingestion rate. The presence of low solids fractions causes a significant increase in the minimum speed required for vortex ingestion of the gas. At low impeller speeds and low solid mass fractions, accumulation of particles in the annulus surrounding the draft-tube reduces the pumping capacity of the impeller. This mechanism also reduces the gas holdup and gas–liquid mass transfer coefficient, although not always in a monotonic fashion. In this design of reactor, aeration results in only a small decrease in the specific power input and so the just-suspended condition is not much affected by the presence of gas.
EXPERIMENTAL ANALYSIS OF BIPARENTAL INBREEDING IN A SELF‐FERTILIZING PLANT

Abstract. — Localized dispersal and mating may genetically structure plant populations, resulting in matings among related individuals. This biparental inbreeding has significant consequences for the evolution of mating systems, yet is difficult to estimate in natural populations. We estimated biparental inbreeding in two populations of the largely self‐fertilizing plant Aquilegia canadensis using standard inference as well as a novel experiment comparing apparent selfing between plants that were randomly relocated within populations to experimental control plants. Using two allozyme markers, biparental inbreeding (b) inferred from the difference between single‐locus and multilocus estimates of selfing (b=ss–sm) was low. Less than 3% of matings involved close relatives (mean b= 0.029). In contrast, randomly relocating plants greatly reduced apparent selfing (mean ss= 0.674) compared to control plants that had been dug up and replanted in their original locations (ss= 0.953, P= 0.002). Based on this difference in ss, we estimated that approximately 30% of all matings involved close relatives (mean b= 0.279, 95% CL = 0.072–0.428). Inference from ss–sm underestimated b in these populations by more than an order of magnitude. Biparental inbreeding is thought to influence the evolution of self‐fertilization primarily through reducing the genetic cost of outcrossing. This is unlikely to be of much significance in A. canadensis because inbreeding depression (a major cost of selfing) is much stronger than the cost of outcrossing. However, biparental inbreeding combined with strong inbreeding depression may influence selection on dispersal.
Thermal and Solvent Stress Cross-Tolerance Conferred to Corynebacterium glutamicum by Adaptive Laboratory Evolution

ABSTRACT Reinforcing microbial thermotolerance is a strategy to enable fermentation with flexible temperature settings and thereby to save cooling costs. Here, we report on adaptive laboratory evolution (ALE) of the amino acid-producing bacterium Corynebacterium glutamicum under thermal stress. After 65 days of serial passage of the transgenic strain GLY3, in which the glycolytic pathway is optimized for alanine production under oxygen deprivation, three strains adapted to supraoptimal temperatures were isolated, and all the mutations they acquired were identified by whole-genome resequencing. Of the 21 mutations common to the three strains, one large deletion and two missense mutations were found to promote growth of the parental strain under thermal stress. Additive effects on thermotolerance were observed among these mutations, and the combination of the deletion with the missense mutation on otsA, encoding a trehalose-6-phosphate synthase, allowed the parental strain to overcome the upper limit of growth temperature. Surprisingly, the three evolved strains acquired cross-tolerance for isobutanol, which turned out to be partly attributable to the genomic deletion associated with the enhanced thermotolerance. The deletion involved loss of two transgenes, pfk and pyk, encoding the glycolytic enzymes, in addition to six native genes, and elimination of the transgenes, but not the native genes, was shown to account for the positive effects on thermal and solvent stress tolerance, implying a link between energy-producing metabolism and bacterial stress tolerance. Overall, the present study provides evidence that ALE can be a powerful tool to refine the phenotype of C. glutamicum and to investigate the molecular bases of stress tolerance.
Patient-Specific Circulating Tumor DNA Detection during Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer.

BACKGROUND In nonmetastatic triple-negative breast cancer (TNBC) patients, we investigated whether circulating tumor DNA (ctDNA) detection can reflect the tumor response to neoadjuvant chemotherapy (NCT) and detect minimal residual disease after surgery. METHODS Ten milliliters of plasma were collected at 4 time points: before NCT; after 1 cycle; before surgery; after surgery. Customized droplet digital PCR (ddPCR) assays were used to track tumor protein p53 (TP53) mutations previously characterized in tumor tissue by massively parallel sequencing (MPS). RESULTS Forty-six patients with nonmetastatic TNBC were enrolled. TP53 mutations were identified in 40 of them. Customized ddPCR probes were validated for 38 patients, with excellent correlation with MPS (r = 0.99), specificity (≥2 droplets/assay), and sensitivity (at least 0.1%). At baseline, ctDNA was detected in 27/36 patients (75%). Its detection was associated with mitotic index (P = 0.003), tumor grade (P = 0.003), and stage (P = 0.03). During treatment, we observed a drop of ctDNA levels in all patients but 1. No patient had detectable ctDNA after surgery. The patient with rising ctDNA levels experienced tumor progression during NCT. Pathological complete response (16/38 patients) was not correlated with ctDNA detection at any time point. ctDNA positivity after 1 cycle of NCT was correlated with shorter disease-free (P < 0.001) and overall (P = 0.006) survival. CONCLUSIONS Customized ctDNA detection by ddPCR achieved a 75% detection rate at baseline. During NCT, ctDNA levels decreased quickly and minimal residual disease was not detected after surgery. However, a slow decrease of ctDNA level during NCT was strongly associated with shorter survival.
Effects of gain- and loss-framed messages on the sun safety behavior of adolescents: The moderating role of risk perceptions

This study examined how message framing effects can be moderated by two types of risk: (a) perceived effectiveness in preventing a risk and (b) perceived susceptibility to the risk. The results indicate that the perceived effectiveness moderated framing effects on the intention to use sunscreen such that a loss-framed message was more effective when perceived effectiveness was low, whereas a gain-framed message was more effective when perceived effectiveness was high. In addition, perceived susceptibility to skin cancer moderated framing effects on the intention to use sunscreen and the intention to wear long pants such that a loss-framed message was more effective when perceived susceptibility was high.
Agreement of high definition oscillometry with direct arterial blood pressure measurement at different blood pressure ranges in horses under general anaesthesia.

OBJECTIVE To determine the agreement of high definition oscillometry (HDO) with direct arterial blood pressure measurements in normotensive, hypotensive and hypertensive horses during general anaesthesia. STUDY DESIGN Experimental study. ANIMALS Seven healthy warmblood horses, aged 3-11 years, weighing 470-565 kg. METHODS Measurements from a HDO device with the cuff placed around the base of the tail were compared with pressures measured invasively from the facial artery. High blood pressures were induced by intravenous (IV) administration of dobutamine (5 μg kg(-1) minute(-1)) over ten minutes followed by norepinephrine (0.1 mg kg(-1) IV) and low pressures by increasing the inspired fraction of isoflurane and administration of nitroglycerine (0.05 mg kg(-1) IV). For analysis three pressure levels were determined: high (MAP>110 mmHg), normal (60 mmHg<MAP<110 mmHg) and low (MAP< 60 mmHg). Bland-Altman analysis was used for comparison between non-invasive and invasive measurements. RESULTS A total of 245 paired measurements of systolic (SAP), mean (MAP) and diastolic (DAP) pressures were obtained. The HDO device underestimated blood pressure at hypertensive and normotensive levels and overestimated blood pressure at hypotensive levels. Best agreement was obtained for SAP and MAP within normotensive limits. At normotension, bias ± standard deviation for SAP, MAP and DAP were 0.1 ± 19.4 mmHg, 0.5 ± 14.0, 4.7 ± 15.6, respectively. At high pressure levels bias and SD were 26.1 ± 37.3 (SAP), 4.2 ± 19.4 (MAP), 1.5 ± 16.8 (DAP) and at low pressures -20.0 ± 20.9 (SAP), -11.4 ± 19.6 (MAP), -4.7 ± 20.1 (DAP), with HDO measurements at a MAP <50 mmHg often failing. CONCLUSION AND CLINICAL RELEVANCE Good agreement with invasive arterial blood pressures was obtained with HDO at normotensive levels in horses. At high and low pressure ranges HDO was unreliable. Therefore, if haemodynamic instability is expected, invasive measurement remains preferable.
Two-dimensional numerical simulation of groundwater contamination in the highway environment

There are many factors that affect the groundwater contamination in the highway environment. This paper reports a two-dimensional numerical simulation of the movement of contamination with water into the sub-grade and water table beneath a road to determine the major factors affecting transport of contaminants. The modelling parameters were assembled from various literature sources and eight scenarios were adopted to simulate the possible controlling conditions. Analyses were undertaken to simulate 2–4 years of water percolation through the pavement sub-structure, some contamination arriving at an underlying ground water table and other arriving at a lateral drain. Overall, the potential for ground water table contamination above probable limit values is very low except in extreme permeability and low sorption cases. Results show, firstly, that the sorption capacity of aggregates should be taken into account, especially as the runoff is likely to be a more important consideration than the possibility of leaching from the pavement's construction layers. Secondly, they show that the permeability of sub-grade soil, the suction-water content characteristics and the partitioning coefficient are the major factors affecting the degree of groundwater contamination in the highway environment. Of these, the sorptive capacity appears to be the key issue. Thirdly, it is shown that the rainfall pattern has little effect if the quantity of rainfall is the same.
Information Technology Competency, Knowledge Processes and Firm Performance

Purpose – The purpose of this paper is to analyze the impact of information technology (IT) competency on knowledge management processes and the relations among IT competency, knowledge management processes and performance outcomes.Design/methodology/approach – The study uses survey data from 162 managers and structural equation modeling to assess the links between IT competency, knowledge management processes and firm performance.Findings – First, this study finds that IT competency plays a critical role in knowledge management processes. Second, knowledge management processes are directly related to market performance, which, in turn, is directly related to financial performance. Third, no direct relation exists between IT competency and firm performance. Knowledge management processes mediate the relation between IT competency and market performance.Research limitations/implications – The research is cross‐sectional, so cause‐effect relations cannot be definitively inferred from the results.Practical i.
Cricopharyngeal Myotomy Normalizes the Opening Size of the Upper Esophageal Sphincter in Cricopharyngeal Dysfunction

Objective: The development of a cricopharyngeal dysfunction is associated with a hypertonic cricopharyngeus (CP) muscle. Therefore, CP myotomy has been advocated by some authors to be an essential part of repair of this condition. However, little objective data exists to show that there is improvement in the upper esophageal sphincter (UES) after CP myotomy. This study assesses the impact of CP myotomy on UES opening.
Do pressure and fatigue influence resident job performance?

Background: Global surveys of residents have consistently identified stress variables as important factors in resident job performance. Aims: Determine whether an association exists between resident stress and job performance. Method: Over a three month period, interns on our inpatient ward services were surveyed regarding their current call schedule, whether their prior night's sleep was sufficient, whether they felt pressed by other commitments, whether they spent enough time teaching medical students and whether they had completed all patient care issues on a given day. Multiple logistic regression was used to assess the association between call status, pressure and sleep adequacy with reported omissions in patient care and adequacy of teaching. Results: In the regression analysis, ratings of high pressure and insufficient sleep but not call status independently predicted outcomes. For example, if an intern felt both pressed and tired, they were over eight times more likely to omit a patient care issue and over four times more likely to report inadequate teaching. Conclusions: Subjective ratings of high pressure and insufficient sleep are associated with poor job performance in medical residents.
Molecular cloning of pneumonia virus of mice

cDNA clones representing nine genes of pneumonia virus of mice (PVM) have been generated. The sizes of the corresponding mRNAs and a provisional transcriptional map of the virus genome have been determined. The apparent gene order is very similar to that of respiratory syncytial virus. The sequences adjacent to the 3' termini of the PVM genes were determined and are very similar to those of respiratory syncytial virus. Several PVM gene polypeptide products have been assigned.
Using the Rasch Model to Measure Students’ Attitudes Toward Science in “Low Performing” Secondary Schools in Malaysia

Normal 0 false false false st1\:*{behavior:url(#ieooui) } The objective of the study was to examine students' attitudes toward learning science in three "low performing" secondary schools in Penang, Malaysia. 214 students from these schools were involved in completing a questionnaire containing items consisting of six constructs. Data collected were analyzed using Rasch modeling. Students in low performing schools tended to have less positive self-concept of science and were unlikely to experience that learning science were related to their future careers. However, students believed that science is useful for society, and experienced that learning science was interesting. Implications for science educators based on these results are discussed.