gebhart/patrepeval huggingface dataset:
Re: Akasaka, H., et al., Molecular anatomy of BCL6 translocations revealed by long-distance polymerase chain reaction-based assays. Cancer Res., 60: 2335-2341, 2000. (2001)

We read with interest the manuscript of Akasaka et al. [(1)][1] on the molecular anatomy of BCL-6 translocations. The authors analyzed 58 cases carrying a BCL-6 rearrangement and defined a break-point hyper-cluster region located downstream of exon 1. In 19 cases, the break point was located between
Organising a conference? Think about what you can do for start-ups! (2016)

ICTR-PHE 2016 welcomed 16 exhibitors and sponsors as part of its industrial exhibition. If you have ever (co-)organised a large scientific conference, you almost certainly have your own list of major industrial actors who could be interested in becoming exhibitors or sponsors. The six start-ups present at ICTR-PHE 2016 – Oncoradiomics, Colnec Health, Dixit Solutions, e-Learning4Health, I-See Computing and SmART Scientific Solutions (not pictured). (Image: Salvatore Fiore) ICTR-PHE has shown that scientific conferences can have a catalysing role in transforming young start-ups and spin-off companies into the key industrial players of tomorrow. A special start-up corner was provided in the industrial exhibition, where small stands were made available for a modest fee to start-ups and spin-off companies in fields relevant to the conference theme, together with a 5-minute timeslot for a pitch to the audience. Six start-ups, from the Netherlands, Italy and France, took this opportunity to present their products and services, which were as varied as Monte Carlo simulation for radiobiology, real-time exchange and collaboration in clinical trials, and e-learning for training in radiotherapy. Beyond the extra visibility for the entrepreneurial researchers behind these start-ups, the initiative also added considerable value for the conference itself: it raised awareness among the participants about the innovative solutions offered by these young companies and effectively demonstrated that being a scientist and an entrepreneur can go hand in hand very well. “It’s very nice to see the scientific community being so supportive towards entrepreneurs,” says Frank Verhaegen, head of research in medical physics at the Maastro clinic in the Netherlands and co-founder of SmART Scientific Solutions, one of the start-ups present at ICTR-PHE 2016. “It’s one of those things that makes you wonder: why doesn’t every conference do this?” If you are organising a conference, why not consider having a start-up corner and making a positive impact on entrepreneurs in your field of research? Don’t hesitate to contact the Knowledge Transfer Group for advice on how to set this up.
A phase I study of GPC3 targeted CAR-T cell therapy in advanced GPC3-expressing hepatocellular carcinoma (HCC). (2023)

TPS624 Background: The mortality of hepatocellular carcinoma (HCC) is increasing worldwide, but outcome of systemic treatments in advanced HCC is suboptimal. Adoptive T-cell transfer therapy represents a promising field that exploits the ability of T-cells to recognize and eliminate their target. Targeting the tumor-associated antigen glypican- 3 (GPC3) through chimeric antigen receptors (CAR) engineered T cells is a mechanistically rational novel treatment for advanced HCC. This study aims to determine the dose and early signals of GPC3 targeted (CAR)-T cells in advanced GPC3 expressing HCC (NCT05003895). Methods: This phase I first in human dose escalation trial will study the safety and feasibility of CAR (hYP7)- T cells in advanced HCC patients expressing GPC3. Eligibility criteria includes advanced HCC, not candidates for curative interventions, progressed on first line systemic treatment, tumor GPC3 positivity of ³ 25% by IHC, Child-Pugh Class A, ³1 measurable lesion, ECOG 0 or 1, adequate organ and marrow function. ParticipantsÕ T cells collected through leukapheresis will be transduced with a lentivirus encoding the CAR construct to generate CAR expressing T cells. Patients receive a conditioning chemotherapy regimen of cyclophosphamide and fludarabine prior to the infusion of the GPC3 directed CAR-T cells (Table). The trial has a 4-level modified Fibonacci dose escalation with a minimum of 3 patients at each level and a 28-day interval between the first three patients. Response will be assessed by imaging every two months during the first year. Patients undergo close monitoring with safety assessments during the first year and are followed for life. The primary objective is to determine the MTD, DLT, safety and feasibility of anti-GPC3 CAR expressing T- cells in patients with GPC3-expressing advanced HCC. Secondary objectives include best overall response and overall survival. Exploratory objectives are multiple and include studies to evaluate the persistence and peak levels of anti-GPC3 CAR-T cells after infusion. Recruitment began in December 2021 and the two patients at dose level -1 has been treated; the planned sample size is 38 patients. Table 1 Dose Level Anti-GPC3 CAR-T Cyclophosphamide (mg/m2) Fludarabine (mg/m2) Level -1 0.3x106 CAR-T per kg bw 200 30 Level 1 0.3x106 CAR-T per kg bw 300 30 Level 2 1x106 CAR-T per kg bw 300 30 Level 3 3x106 CAR-T per kg bw 300 30. Clinical trial information: NCT05003895 .
Neurotrophically Induced Mesenchymal Progenitor Cells Derived from Induced Pluripotent Stem Cells Enhance Neuritogenesis via Neurotrophin and Cytokine Production (2017)

Adult tissue-derived mesenchymal stem cells (MSCs) are known to produce a number of bioactive factors, including neurotrophic growth factors, capable of supporting and improving nerve regeneration. However, with a finite culture expansion capacity, MSCs are inherently limited in their lifespan and use. We examined here the potential utility of an alternative, mesenchymal-like cell source, derived from induced pluripotent stem cells, termed induced mesenchymal progenitor cells (MiMPCs). We found that several genes were upregulated and proteins were produced in MiMPCs that matched those previously reported for MSCs. Like MSCs, the MiMPCs secreted various neurotrophic and neuroprotective factors, including brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), leukemia inhibitory factor (LIF), osteopontin, and osteonectin, and promoted neurite outgrowth in chick embryonic dorsal root ganglia (DRG) cultures compared with control cultures. Cotreatment with a pharmacological Trk-receptor inhibitor did not result in significant decrease in MiMPC-induced neurite outgrowth, which was however inhibited upon Jak/STAT3 blockade. These findings suggest that the MiMPC induction of DRG neurite outgrowth is unlikely to be solely dependent on BDNF, but instead Jak/STAT3 activation by IL-6 and/or LIF is likely to be critical neurotrophic signaling pathways of the MiMPC secretome. Taken together, these findings suggest MiMPCs as a renewable, candidate source of therapeutic cells and a potential alternative to MSCs for peripheral nerve repair, in view of their ability to promote nerve growth by producing many of the same growth factors and cytokines as Schwann cells and signaling through critical neurotrophic pathways. Stem Cells Translational Medicine 2018;7:45-58.
Interleukin-18-induced Human Coronary Artery Smooth Muscle Cell Migration Is Dependent on NF-κB- and AP-1-mediated Matrix Metalloproteinase-9 Expression and Is Inhibited by Atorvastatin (2006)

The proliferation and migration of arterial smooth muscle cells (SMCs) are key events in the vascular restenosis that frequently follows angioplasty. Furthermore, SMC migration and neointimal hyperplasia are promoted by degradation of the extracellular matrix by matrix metalloproteinases (MMPs). Because we demonstrated previously that the proinflammatory and proatherogenic cytokine interleukin-18 (IL-18) stimulates SMC proliferation (Chandrasekar, B., Mummidi, S., Valente, A. J., Patel, D. N., Bailey, S. R., Freeman, G. L., Hatano, M., Tokuhisa, T., and Jensen, L. E. (2005) J. Biol. Chem. 280, 26263-26277), we investigated whether IL-18 induces SMC migration in an MMP-dependent manner and whether the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor atorvastatin can inhibit this response. IL-18 treatment increased both mRNA and protein expression of MMP9 in human coronary artery SMCs. Gel shift, enzyme-linked immunosorbent, and chromatin immunoprecipitation assays revealed a strong induction of IL-18-mediated AP-1 (c-Fos, c-Jun, and Fra-1) and NF-kappaB (p50 and p65) activation and stimulation of MMP9 promoter-dependent reporter gene activity in an AP-1- and NF-kappaB-dependent manner. Ectopic expression of p65, c-Fos, c-Jun, and Fra-1 induced MMP9 promoter activity. Specific antisense or small interfering RNA reagents for these transcription factors reduced IL-18-mediated MMP9 transcription. Furthermore, IL-18 stimulated SMC migration in an MMP9-dependent manner. Atorvastatin effectively suppressed IL-18-mediated AP-1 and NF-kappaB activation, MMP9 expression, and SMC migration. Together, our results indicate for the first time that the proatherogenic cytokine IL-18 induces human coronary artery SMC migration in an MMP9-dependent manner. Atorvastatin inhibits IL-18-mediated aortic SMC migration and has therapeutic potential for attenuating the progression of atherosclerosis and restenosis.
Schedule-dependent synergism between raltitrexed and irinotecan in human colon cancer cells in vitro. (1998)

The quinazoline folate analogue raltitrexed (ZD1694; Tomudex) and the camptothecin derivative irinotecan are two new agents showing clinical activity against colorectal cancer. To identify the optimal conditions to achieve synergistic cytotoxicity before the clinical development of their combination, we explored the interactions between ZD1694 and the active metabolite of irinotecan, 7-ethyl-10-hydroxycamptothecin (SN-38), in vitro. Cytotoxicity was evaluated with a clonogenic assay using the human colon cancer cell line HCT-8. Different schedules of administration and different dose ratios of the two agents were compared and evaluated for synergism, additivity, or antagonism with a quantitative method based on the median-effect principle of Chou and Talalay (T. C. Chou and P. Talalay, Adv. Enzyme Regul., 22: 27-55, 1984). Sequential short-term (1 and 4-h) exposures to SN-38 followed by ZD1694 resulted in synergistic cytotoxicity at broad dose-effect ranges. At a high level of cell kill, the synergism was greater when either equiactive doses of the two agents or higher relative doses of ZD1694 were used. A 24-h interval between exposure to SN-38 and ZD1694 significantly enhanced the magnitude of the synergy (P = 0.001). The opposite sequence or simultaneous exposures produced significantly less potentiation or nearly additive interactions (P = 0.0006 and P < 0.0001). The synergism was completely lost under conditions of more prolonged drug exposure (24-h continuous exposure). In conclusion, in this in vitro model of human colon cancer, ZD1694 and SN-38 produced synergistic cytotoxicity. Our findings support the clinical use of this combination and provide a rationale for a clinical trial using sequential short-term exposures to equiactive doses of SN-38 and ZD1694 administered sequentially with a 24-h interval.
Electrospun Chitosan Functionalized with C12, C14 or C16 Tails for Blood-Contacting Medical Devices (2022)

Medical applications stimulate the need for materials with broad potential. Chitosan, the partially deacetylated derivative of chitin, offers many interesting characteristics, such as biocompatibility and chemical derivatization possibility. In the present study, porous scaffolds composed of electrospun interwoven nanometric fibers are produced using chitosan or chitosan functionalized with aliphatic chains of twelve, fourteen or sixteen methylene groups. The scaffolds were thoroughly characterized by SEM and XPS. The length of the aliphatic tail influenced the physico-chemical and dynamic mechanical properties of the functionalized chitosan. The electrospun membranes revealed no interaction of Gram+ or Gram- bacteria, resulting in neither antibacterial nor bactericidal, but constitutively sterile. The electrospun scaffolds demonstrated the absence of cytotoxicity, inflammation response, and eryptosis. These results open the door to their application for blood purification devices, hemodialysis membranes, and vascular grafts.
Pladienolides, New Substances from Culture of Streptomyces platensis Mer-11107 III. In Vitro and In Vivo Antitumor Activities (2004)

We have discovered seven novel 12-membered macrolides, pladienolides A to G, from Streptomyces platensis Mer-11107, with pladienolide B the most potently inhibiting hypoxia induced-VEGF expression and proliferation of the U251 cancer cell line. A growth inhibitory study using a 39-cell line drug-screening panel demonstrated that pladienolide B has strong antitumor activities in vitro. A COMPARE analysis reveals that it has a unique antitumor spectrum that sets it apart from anticancer drugs currently in clinical use. This result suggests that pladienolide B has a novel mechanism of action. A series of xenograft studies were conducted to evaluate the in vivo potency of pladienolides. Pladienolide B extensively inhibited tumor growth in xenograft models. In the most sensitive model, using BSY-1 xenografts, tumors were completely regressed by administration of pladienolide B. For the reason of their novel mechanism of action and excellent in vivo efficacy, pladienolides appear to have major potential for use in cancer treatment.
Immunizing against Anogenital Cancer: HPV Vaccines (2016)

Most of us are familiar with foot and hand warts caused by the skin tropic human papillomaviruses (HPV). However, it is less well recognized that infection with HPV types that replicate in the anogenital mucosa is the most prevalent sexually transmitted disease in the world. Indeed, a recent estimate suggests that 80%-90% of the sexually active population is exposed during their lifetime to mucosal HPV Of the more than 40 genotypes of mucosal HPV, most result in benign and transient disease, such as genital warts caused by HPV types 6 and 11. However, 15 HPV genotypes (e.g., HPV types 16 and 18) are classified as high-risk because they are causal agents of human cancers Almost all of the half million cervical cancer cases that occur worldwide each year are related to infection with high-risk HPV (hrHPV) High-risk HPVs, most especially HPV16, are also implicated in the development of some anal, oropharyngeal, vaginal, vulval, and penile cancers. Within a given population, the most prevalent hrHPV genotype varies with geographical location Combined, all of the hrHPVs are responsible for approximately 5% of all cancers worldwide (10% in women) [1-3]. HPV infection is a significant health burden on the United States economy, costing approximately US $7.6 billion per year for screening (Pap smear) and cervical cancer treatment Recommendations for the current vaccines are for routine inoculation of females 13-26 years of age as well as males 13-21 years of age. The vaccines are most effective when administered prior to potential virus exposure (i.e., before commencement of sexual activity) Vaccination is the most effective strategy to prevent these cancers and associated morbidities
High Density and Low-Temperature Interconnection Enabled by Mechanical Self-Alignment and Electroless Plating (2019)

In this work, we propose and demonstrate the use of metal electroless plating along with mechanical self-alignment as a method to create high density scalable interconnects between chiplets using a low temperature process flow. Void free and selective bonding of a copper pillar array at 50 ^m pitch using electroless nickel deposition is demonstrated at a temperature of 95°C and atmospheric pressure. Mechanical self-alignment using precision ruby balls is demonstrated to attain alignment accuracies within 2 μm.
Quantitative PET/CT for radiomics (2019)

The conversion of images, such as those from positron emission tomography (PET) and x-ray computed tomography (CT), into mineable high-dimensional data is known as radiomics. Radiomics is motivated by the concept that biomedical images contain information that reflects underlying physiology and molecular biology, and that these relationships can be revealed via quantitative image analyses. Thus an understanding of quantitative PET/CT accuracy, and how variations in acquisition and image reconstruction parameters influence imaging features in the absence of true underlying biologic effects, is essential to PET/CT radiomics. In this chapter, we first provide an overview of quantitative PET/CT, with emphasis on uncertainties and their clinical impact on quantitative precision and accuracy. We highlight ongoing efforts towards PET/CT standardization and harmonization as part of quantitative imaging biomarker quality assurance programs. With a basis in quantitative PET/CT, we introduce PET/CT radiomics, list additional sources of radiomic data processing uncertainty, propose guidelines to improve transparent reporting of PET/CT radiomic features, and emphasize the growing need for robust omics data analytics to help ensure reproducibility and clinical translation of scientific findings. Lastly, we summarize future directions beyond PET/CT radiomics, including PET/MR radiomics, non-FDG-PET radiomics, normal tissue function PET radiomics, and deep learning of PET/CT images.
Abstract 704: Cardiac Progenitor Cell Aging Is Responsible for Organ Aging (2007)

To establish whether the aging cardiomyopathy is dictated by depletion of the cardiac progenitor cell (CPC) pool and accumulation of old myocytes, we measured first the number of CPCs in rats at 4, 12, 20 and 28 months of age. CPCs are lineage-negative cells that express the stem cell antigens c-kit, MDR-1 and/or Sca-1. Unexpectedly, from 4 to 28 months, the number of CPCs in the heart increased ~3-fold. The increase in mitotic index of CPCs in the old heart indicated enhanced activation of CPCs which resulted in an increased number of myocyte progenitors and precursors and ultimately differentiated cardiomyocytes. These observations were at variance with the concomitant accumulation of p16 INK4a -positive-myocytes and the 6-fold increased rate of myocyte apoptosis in the senescent heart pointing to defects in the CPC compartment with aging. Activation and differentiation of old CPCs may generate a myocyte progeny that rapidly reaches senescence. To evaluate the biological age of CPCs, we measured two parameters of cellular aging: the senescence-associated protein p16 INK4a and telomere length. From 4 to 28 month, p16 INK4a -positive-CPCs increased from ~6% to ~81% resulting in a sharp decrease in the number of functionally-competent CPCs. Telomere length was measured by Q-FISH in cytospin preparations of c-kit-positive-cells collected from hearts at 3 and 27 months. In old hearts, the distribution of telomere length in CPCs, myocyte progenitors-precursors and developing myocytes was shifted to the left towards shorter telomeres. Average telomere length in old CPCs, myocyte progenitors-precursors and developing myocytes was 30%, 38% and 52% shorter than in the corresponding young cell populations, respectively. Importantly, 55% of old CPCs and 15% of young CPCs had telomeres less than 8 kbp and were p16 INK4a -positive. Thus, telomere attrition in CPCs with age leads to the generation of a myocyte progeny that rapidly acquires the senescent phenotype. However, nearly 16% of the old CPC pool had telomeres greater than 14 kbp pointing to a relevant growth reserve of the senescent myocardium. In conclusion, CPC aging with reduction in telomeric length dictates the formation of a senescent progeny which conditions organ aging and failure.
AUTOMATED PROCESS CONTROL FOR CAPACITOR-DISCHARGE WELDING (2023)

Capacitor discharge welding (CDW) is an autogenous, rapid solidification, joining process ideal for joining small parts of similar or dissimilar metals. Potential applications include welding of electrical contacts, cutting tool inserts, and automotive valves. Because of high cooling rates in excess of one million &deg;C/s, the production rate for CDW process is very high. However, potential industrial users have been hesitant to use CDW due largely to the unavailability of automated process control. The objective of this research was to develop models for an on-line quality control feedback system for CDW. The system described monitors current and voltage curves produced during the welding cycle. These curves have been found to be good indicators of certain types of welding defects. A closed-loop automation architecture for future work will also be discussed.
Genotype × Environment Interaction for Grain Color in Hard White Spring Wheat (2003)

Improvement of grain color in hard white spring wheat (Triticum aestivum L.) breeding programs depends on understanding the influences of genotype (G), environment (E), and their interaction (G × E). The objectives of this study were to quantify genetic variability for grain color and assess the nature of the G × E interaction in determining grain color in 79 spring wheat genotypes. Twelve check cultivars [seven hard red (HR), four hard white (HW), and one soft white (SW)] and 67 white-seeded Australian (AUS) accessions were grown at two locations across 2 yr. Wheat genotypes differed significantly in agronomic traits, grain protein, and kernel hardness. Grain and meal color were quantified using Hunterlab colorimeter values. Whole grain color values without (L = 40.9–50.4 units; a = 7.0–8.3; b = 13.6–19.1) and with NaOH treatment (L = 22.7–38.1; a = 7.7–9.7; b = 9.2–17.9) varied among genotypes. Using ground meal, color values (L = 80.1–84.9; a = 1.8–2.6; b = 8.9–11.8), yellow pigment content (2.5–4.8 μg g−1), and lutein content (1.8–3.7 μg g−1) varied among genotypes. Genotype × location (L) interactions were not significant for colorimetric and pigmentation variables. The Azallini and Cox test detected one crossover G × year (Y) interaction for grain a-value (without NaOH), one for grain b-value (without NaOH), and 12 for lutein content. Genetic variation exists for grain color among HW genotypes. The noncrossover nature of G × E interactions for grain color indicates that white-seeded genotypes selected as superior in one environment will be superior in other environments.
Electronic Conduction in Liquid Crystals and Materials Design for its Characterization and Device Application in the Future (2004)

In these ten years, two separate groups including the author's discovered the electronic conduction in liquid crystals, whose electrical conduction had been believed to be ionic for a long time. Since then, we have synthesized model compounds and characterized their charge carrier transport properties in order to establish the scientific basis for their device application in the future. In this article, the updated understanding of electrical conduction in liquid crystals is reviewed in relation to the model materials synthesized. This demonstrates a high potential of liquid crystals as a new class of quality organic semiconductors, i.e., Self-organizing Molecular Semiconductor.
Far from MCAR (2020)

Estimation of population-level disease burden and control requires appropriate adjustment for missing data. Even in large studies with limited missingness, estimates relying on the MCAR assumption or baseline stratification should be interpreted cautiously.
Graft-Versus-Leukemia Effect of Allogeneic Stem-Cell Transplantation and Minimal Residual Disease in Patients With Acute Myeloid Leukemia in First Complete Remission (2017)

The graft-versus-leukemia effect of alloHSCT is equally present in MRD-positive and MRD-negative patients, which advocates a personalized application of alloHSCT, taking into account the risk of relapse determined by AML risk group and MRD status, as well as the counterbalancing risk of nonrelapse mortality.