Miracle-dz/UniFAR-FTUs huggingface dataset:
Is there a graft‐versus‐leukaemia effect in the absence of graft‐versus‐host disease in patients undergoing bone marrow transplantation for acute leukaemia?

During a 13‐year period, 5200 autografts, 1039 HLA‐identical sibling transplants without acute or chronic graft‐vs.‐host disease (GVHD) and 67 twins were reported to the European Group for Blood and Marrow Transplantation EBMT. Follow‐up time was a median of 32 months. Diagnoses were acute myeloid leukaemia (AML, 4521) and acute lymphoblastic leukaemia (ALL, 1785) in first complete remission. The probability of relapse at 5 years was 51 ± 1% in the autografts, 45 ± 8% in the twins and 34 ± 2% among the HLA‐identical siblings (auto vs. sibs, P < 0·0001). In multivariate analyses, the following factors were significantly associated with an increased risk of relapse: ALL vs. AML M3 [relapse rate (RR) 2·29, P < 0·0001], AML non‐M3 vs. AML M3 (RR 1·8, P < 0·0001), autograft vs. sibling transplant (RR 1·76, P < 0·0001), interval diagnosis to transplantation < 261 d (RR 1·45, P < 0·001) and other conditioning vs. total body irradiation (RR 1·16, P = 0·001). Transplant‐related mortality was the same in the three groups at approximately 10% at 2 years. Five‐year leukaemia‐free survival was 42 ± 1% in the autografts, 44 ± 8% in the twins and 58 ± 2% among the siblings (auto vs. sibs, P < 0·0001). The factors significant for relapse were also significant in multivariate analyses for leukaemia‐free survival. In addition, children had a significantly better leukaemia‐free survival than adults (RR 0·82, P < 0·0001). Recipients of bone marrow from HLA‐identical siblings without GVHD had a lower risk of relapse and a better leukaemia‐free survival than recipients of autografts. This may be as a result of a graft‐vs.‐leukaemia effect in the absence of GVHD.
Selection of underfill material in Cu hybrid bonding and its effect on the transistor keep-out-zone

Hybrid bonding of Cu with PECVD oxide (PE-TEOS), benzocyclobutane (BCB), and polyimide (PI) is gaining importance in third dimensional IC fabrication. Thermal mechanical simulation is performed on Cu hybrid bonding structure as the gap-filling materials are not thermally matched to the back-end-of-line (BEOL) materials. Two bonded Si layer connected by TSV with different underfill materials are compared with metal bonding without underfill. Stress profile in the Si substrate for back-to-face and face-to-face bonding orientations is extracted. By using the piezoresistive equation, keep-out-zone (KOZ) for MOS transistor is estimated. TEOS is found to be able to minimize the mobility change for n-MOSFET but similar effect is not observed in p-MOSFET. Mobility change when organic polymer (BCB or PI) underfill is used shows dependency on the via diameter and channel orientation. This study provides a guideline for transistor placement in hybrid bonding to minimize mobility change.
Quantitative Structure−Activity Relationship of Botanical Sesquiterpenes: Spatial and Contact Repellency to the Yellow Fever Mosquito, Aedes aegypti

The plant terpenoids encompass a diversity of structures and have many functional roles in nature, including protection against pest arthropods. Previous studies in this laboratory have identified naturally occurring sesquiterpenes contained in essential oils from two plants, amyris (Amyris balsamifera) and Siam-wood (Fokienia hodginsii), that are significantly repellent to a spectrum of arthropod pests. In efforts to further examine the biological activity of this class of compounds 12 of these plant-derived sesquiterpenes have been isolated, purified, and assayed for spatial and contact repellency against the yellow fever mosquito, Aedes aegypti. These data were used to develop quantitative structure−activity relationships that identified key properties of the sesquiterpene molecule, including electronic and structural parameters that were used to predict optimal repellent activity. There were notable similarities in the models developed for spatial repellency over five time points and for contact repel.
Efficient Clustering from Distributions over Topics

There are many scenarios where we may want to find pairs of textually similar documents in a large corpus (e.g. a researcher doing literature review, or an R&D project manager analyzing project proposals). To programmatically discover those connections can help experts to achieve those goals, but brute-force pairwise comparisons are not computationally adequate when the size of the document corpus is too large. Some algorithms in the literature divide the search space into regions containing potentially similar documents, which are later processed separately from the rest in order to reduce the number of pairs compared. However, this kind of unsupervised methods still incur in high temporal costs. In this paper, we present an approach that relies on the results of a topic modeling algorithm over the documents in a collection, as a means to identify smaller subsets of documents where the similarity function can then be computed. This approach has proved to obtain promising results when identifying similar documents in the domain of scientific publications. We have compared our approach against state of the art clustering techniques and with different configurations for the topic modeling algorithm. Results suggest that our approach outperforms (> 0.5) the other analyzed techniques in terms of efficiency.
Oncogenic EGFR Signaling Networks in Glioma

EGFR and downstream signaling networks contribute to the hallmark characteristics of glioma. The epidermal growth factor receptor (EGFR) is a transmembrane protein that regulates many fundamental cellular processes, including growth, survival, and migration. EGFR is amplified, overexpressed, or mutated in various types of cancer, resulting in the deregulation of these critical cellular processes. In this Review, which has four figures and 120 citations, we examine the mechanisms by which EGFR contributes to oncogenic transformation in an aggressive form of brain tumor (glioblastoma) and discuss the limitations of current treatment strategies. Finally, we offer an outlook on how these therapies may be improved through the use of systems biology. The epidermal growth factor receptor (EGFR) is a primary contributor to glioblastoma (GBM) initiation and progression. Here, we examine how EGFR and key downstream signaling networks contribute to the hallmark characteristics of GBM such as rapid cancer cell proliferation and diffused invasion. Additionally, we discuss current therapeutic options for GBM patients and elaborate on the mechanisms through which EGFR promotes chemoresistance. We conclude by offering a perspective on how the potential of integrative systems biology may be harnessed to develop safe and effective treatment strategies for this disease.
A Ubiquinone-binding Site Regulates the Mitochondrial Permeability Transition Pore*

We have investigated the regulation of the mitochondrial permeability transition pore (PTP) by ubiquinone analogues. We found that the Ca2+-dependent PTP opening was inhibited by ubiquinone 0 and decylubiquinone, whereas all other tested quinones (ubiquinone 5, 1,4-benzoquinone, 2-methoxy-1,4-benzoquinone, 2,3-dimethoxy-1,4-benzoquinone, and 2,3-dimethoxy-5,6-dimethyl-1,4-benzoquinone) were ineffective. Pore inhibition was observed irrespective of the method used to induce the permeability transition (addition of Pi or atractylate, membrane depolarization, or dithiol cross-linking). Inhibition of PTP opening by decylubiquinone was comparable with that exerted by cyclosporin A, whereas ubiquinone 0 was more potent. Ubiquinone 5, which did not inhibit the PTP per se, specifically counteracted the inhibitory effect of ubiquinone 0 or decylubiquinone but not that of cyclosporin A. These findings define a ubiquinone-binding site directly involved in PTP regulation and indicate that different quinone structural features are required for binding and for stabilizing the pore in the closed conformation. At variance from all other quinones tested, decylubiquinone did not inhibit respiration. Our results define a new structural class of pore inhibitors and may open new perspectives for the pharmacological modulation of the PTP in vivo.
Monooxygenase Levels and Knockdown Resistance (kdr) Allele Frequencies in Anopheles gambiae and Anopheles arabiensis in Kenya

Abstract Pyrethroid-treated bed-nets and indoor spray are important components of malaria control strategies in Kenya. Information on resistance to pyrethroid insecticides in Anopheles gambiae and An. arabiensis populations is essential to the selection of appropriate insecticides and the management of insecticide resistance. Monooxygenase activity and knockdown resistance (kdr) allele frequency are biochemical and molecular indicators of mosquito resistance to pyrethroids. This study determined baseline information on monooxygenase activity and kdr allele frequency in anopheline mosquitoes in the western region, the Great Rift Valley–central region, and the coastal region of Kenya. In total, 1,990 field-collected individuals, representing 12 An. gambiae and 22 An. arabiensis populations were analyzed. We found significant among-population variation in monooxygenase activity in An. gambiae and An. arabiensis and substantial variability among individuals within populations. Nine of 12 An. gambiae populations exhibited significantly higher average monooxygenase activity than the susceptible Kisumu reference strain. The kdr alleles (L1014S) were detected in three An. gambiae populations, and one An. arabiensis population in western Kenya, but not in the Rift Valley–central region and the coastal Kenya region. All genotypes with the kdr alleles were heterozygous, and the conservative estimation of kdr allele frequency was below 1% in these four populations. Information on monooxygenase activity and kdr allele frequency reported in this study provided baseline data for monitoring insecticide resistance changes in Kenya during the era when large-scale insecticide-treated bed-net and indoor residual spray campaigns were being implemented.
Synthesis of a new photoreactive derivative of dipyridamole and its use in the manufacture of artificial surfaces with low thrombogenicity.

Photoimmobilization of dipyridamole (Persantin) was accomplished through the use of a new synthetic conjugate molecule, 1. Persantin is a powerful inhibitor of platelet activation and aggregation and is widely used as a vasodilator. Conjugate 1 consists of triply protected dipyridamole [three of the four hydroxyl groups carry a tert-butyldimethylsilyl (TBDMS) protective group) and the photoreactive 4-azidobenzoyl group. A short hydrophilic spacer chain, derived from triethylene glycol, separates the protected dipyridamole system and the photoreactive group. Compound 1 was immobilized on polyurethane sheets (Pellethane D-55) through irradiation with ultraviolet (UV) light, and the protective groups were removed afterward. The resulting modified polyurethane surfaces were characterized by different physicochemical techniques: UV extinction, contact angle measurements (captive bubble technique), and X-ray photoelectron spectroscopy (XPS). The UV extinction measurements showed the presence of 13 +/- 1 nmol of immobilized dipyridamole/cm2. The contact angle measurements revealed that the modified surface was markedly more hydrophilic than the control (i.e. unmodified polyurethane). XPS measurements clearly established the presence of immobilized dipyridamole in the outermost layers of the modified surface. This was especially clear from the XPS spectra recorded at a low take-off angle (approximately 6 degrees). Furthermore, the XPS spectra showed that the TBDMS protective groups had been quantitatively removed during the deprotection/washing treatment. The in vitro blood compatibility of the modified surface was studied with the thrombin generation assay as developed in our group, as well as with scanning electron microscopy. The thrombin generation test produced a lag time of 1275 s for the modified surface, as opposed to 569 s for the control. Scanning electron microscopy showed that far fewer platelets adhere to the modified surface (approximately 7 x 10(3)/mm2) as compared to the control (approximately 6 x 10(2)/mm2). Taken together, the experimental data reveal that the modified surface has excellent blood compatibility in vitro. It is discussed that the use of conjugate 1 leads to simultaneous exposure of dipyridamole at the modified surface and to a marked increase of the surface hydrophilicity, which is likely to hamper adsorption of plasma proteins. The combination of these effects is uniquely related to the molecular buildup of 1. Conjugate 1 will be used in future work that is aimed at preparing small-caliber polyurethane vascular grafts with a blood compatible lumenal surface.
Phase 2 study of mitozantrone in combination with chlorambucil and prednisolone for relapsed and refractory non‐Hodgkins lymphoma

Thirty‐six patients with non‐Hodgkin's lymphoma (NHL) (comprising patients with refractory or relapsed disease and eight elderly, unfit patients with de novo disease) were treated with mitozantrone, chlorambucil and prednisolone on an out‐patient basis. Fifteen patients had low grade (LG) disease, five patients intermediate grade (IG) disease and 16 patients high grade (HG) disease and 31/36 had stage IV disease. All elderly patients had IG or HG disease. The regimen was well‐tolerated. After six courses of chemotherapy, there was a 69 per cent response rate with 33 per cent in complete remission. The median duration of remission was 15 months. The overall 3‐year projected survival was 38 per cent; 27 per cent for LG disease and 47 per cent for HG and IG disease. Responses did not appear durable for either HG or LG disease unless CR was achieved early on. Three of the eight patients treated de novo (mean age 71 years) have survived, disease‐free, between 28 and 38 months from entry. This study indicates that mitozantrone‐based regimens have promising activity in NHL and require further evaluation. The low toxicity combined with worthwhile remissions make this an attractive first‐line option for elderly patients.
The Manitoba Inflammatory Bowel Disease Cohort Study: a prospective longitudinal evaluation of the use of complementary and alternative medicine services and products

Objective To determine the prevalence of complementary and alternative medicine (CAM) use over time in a population-based cohort of patients with inflammatory bowel disease (IBD). Methods The Manitoba IBD Cohort Study is a longitudinal, population-based study of multiple determinants of health outcomes in an IBD cohort. Participants completed semi-annual surveys, and annual in-person interviews. Enquiries about the use of 12 types of CAM service providers and 13 CAM products, based on items from a national survey, were included at months 0, 12, 30 and 54. Results Overall, 74% of respondents used a CAM service or product in the 4.5-year period, with approximately 40% using some type of CAM at each time point, and 14% using CAM consistently at every time point. There was a trend for women to use CAM more than men; there was no difference in CAM use between patients with Crohn's disease and those with ulcerative colitis. The most often used CAM services (on average) were massage therapy (30%) and chiropractic (14%), physiotherapy (4%), acupuncture (3.5%) and naturopathy/homeopathy (3.5%). A wide range of CAM products were used, with Lactobacillus acidophilus (8%), fish and other oils (5.5%), glucosamine (4%) and chamomile (3.5%) as the most common. On average, only 18% of consumers used CAM for their IBD, so the majority chose it for other problems. There were no differences in psychological variables between CAM users and non-users. Conclusions Those with IBD commonly try CAM, although very few use these approaches regularly over the years. CAM is not usually used by patients with IBD for disease management, but clinicians should be aware that many will test the services and products.
Quantifying the performance impact of large pages on in-memory big-data workloads

In-memory big-data processing is rapidly emerging as a promising solution for large-scale data analytics with high-performance and/or real-time requirements. In-memory big-data workloads are often hosted on servers that consist of a few multi-core CPUs and large physical memory, exhibiting the non-uniform memory access (NUMA) characteristics. While large pages are commonly known as an effective technique to reduce the performance overheads of virtual memory and widely supported across the modern hardware and system software stacks, relatively little work has been done to investigate their performance impact on in-memory big-data workloads hosted on NUMA systems. To bridge this gap, this work quantifies the performance impact of large pages on in-memory big-data workloads running on a large-scale NUMA system. Our experimental results show that large pages provide no or little performance gains over the 4KB pages when the in-memory big-data workloads process sufficiently large datasets. In addition, our experimental results show that large pages achieve higher performance gains as the dataset size of the in-memory big-data workloads decreases and the NUMA system scale increases. We also discuss the possible performance optimizations for large pages and estimate the potential performance improvements.
Captopril-polyethyleneimine conjugate modified gold nanoparticles for co-delivery of drug and gene in anti-angiogenesis breast cancer therapy

Captopril-polyethyleneimine (CP) containing low molecular weight polyethyleneimine and anti-angiogenesis drug captopril conjugated via an amide bond was fabricated to modify gold nanoparticles and complex with siRNA to construct siRNA/CP/GNP complexes for the co-delivery of drug and siRNA in anti-angiogenesis breast cancer therapy. The self-assembled siRNA/CP/GNP complexes exhibited desirable and homogenous particle size, reasonable positive charges and condensation ability, and effective gene-silencing property in vitro. In addition, siRNA/CP/GNP complexes co-delivering captopril and siRNA achieved combined angiogenesis suppression by more effectively downregulating the expression of vascular endothelial growth factor mRNA and protein via different pathways in vitro, as compared to mono-delivery systems. In vivo investigation on nude mice bearing MDA-MB435 tumor xenografts revealed that siRNA/CP/GNP complexes possessed satisfying tumor homing ability and strong antitumor activity. These findings suggested that siRNA/CP/GNP complexes could be an ideal system for simultaneous transfer of drug and siRNA, which might be a new promising strategy for effective breast cancer therapy.
A correlation‐based method for extracting subject‐specific components and artifacts from group‐fMRI data

We present a simple but effective correlation‐based method (maxCorr) for extracting subject‐specific components from group‐fMRI data. The method finds signal components that correlate maximally with the data set of one subject and minimally with the data sets of the other subjects. We show that such subject‐specific components are often related to movement and physiological noise (e.g. cardiac cycle, respiration). We further demonstrate that removing the most subject‐specific components for each subject reduces the overall data variance and improves the statistical identification of true fMRI activations. We compare the performance of maxCorr with CompCor, a commonly used artifact‐finding method in fMRI analysis. We show that maxCorr is less likely than CompCor to remove actual stimulus‐related activity, especially when no information about the stimulus is available. MaxCorr operates without stimulus information and is therefore well suitable for analyses of fMRI experiments employing naturalistic stimuli, such as movies, where stimulus regressors are difficult to construct, and for brain decoding techniques benefiting from reduced subject‐specific variance in each subject's data.
Real-Time High-Resolution Compound Imaging Allows Percutaneous Initiation and Surveillance in an Orthotopic Murine Pancreatic Cancer Model

Objectives: Orthotopic tumor models are regarded as being suitable for preclinical research on pancreatic cancer. The anatomic localization of the tumor in the retroperitoneum, however, provides little possibility for monitoring tumor growth. Methods: To assess time-related changes in orthotopic tumor volume, we applied transabdominal high-resolution compound imaging to the murine pancreas. A 15-MHz ultrasound probe was used to determine the feasibility of real-time transabdominal high-resolution ultrasonography to initiate tumor growth by inoculation of pancreatic tumor cells into the pancreas and monitor tumor growth, as well as use as a tool for assessing response to chemotherapy. Results: High-resolution ultrasound allows for precise tumor inoculation in the pancreas. Sonographic-evaluated tumor weight was found to be closely related to actual tumor weight (R = 0.97) measured during necropsy. Conclusions: High-resolution real-time compound imaging substitutes killing of mice during longitudinal studies and can be used for minimizing animal consumption because each mouse can be followed in an experimental group rather than having to resort to euthanasia for tissue harvesting.
ACASI and Face-to-Face Interviews Yield Inconsistent Estimates of Domestic Violence Among Women in India: The Samata Health Study 2005-2009

Background. Audio computer-assisted self-interviews (ACASI) are increasingly used in health research to improve the accuracy of data on sensitive behaviors. However, evidence is limited on its use among low-income populations in countries like India and for measurement of sensitive issues such as domestic violence. Method. We compared reports of domestic violence and three less sensitive behaviors related to household decision making and spousal communication in ACASI and face-to-face interviews (FTFI) among 464 young married women enrolled in a longitudinal study of gender-based power and adverse health outcomes in low-income communities in Bangalore, India. We used a test-retest design. At the 12-month study visit, we elicited responses from each participant through FTFI first, followed by ACASI. At the 24-month visit, we reversed the order, implementing ACASI first, followed by FTFI. Univariable log-linear regression models and kappa statistics were used to examine ACASI’s effects on self-reports. Results. Regression results showed significantly lower reporting in ACASI relative to FTFI at both visits, including for domestic violence (12-month risk ratio [RR] = 0.61, 95% CI = 0.52, 0.73; 24-month RR = 0.74, 95% CI = 0.62, 0.89). Response agreement between interview modes, calculated by kappa scores, was universally low, though highest for domestic violence (12-month κ = 0.45; 24-month κ = 0.48). Older age and greater educational attainment appeared associated with higher response agreement. Conclusions. Greater reporting in FTFI may be due to social desirability bias for the less sensitive questions and perceptions of therapeutic benefit for domestic violence. These results cast doubt on the appropriateness of using ACASI for measurement of sensitive behaviors in India.