gebhart/patrepeval huggingface dataset:
Outcomes with lower intensity therapy in TP53-mutated AML. (2017)

7017 Background: TP53 mutations confer an adverse prognosis in patients (pts) with AML treated with standard chemotherapy. A recent study reported high response rates using a 10-day regimen of decitabine (DAC10) in pts with TP53-mutated ( TP53-MUT) AML. The question remains whether this benefit is unique to DAC10 or whether the same benefit among TP53-MUT AML applies to other low intensity therapy (Rx). Methods: We reviewed our own experience of pts treated with low intensity Rx from 2012 - 2016. Mutation testing was performed using a whole-exome sequencing panel. We reviewed the clinico-pathologic characteristics of these pts, and compared their outcomes based on the presence/absence of a TP53mutation and by the type of Rx they received. Results: There were 131 pts in our cohort of which 33 (25%) had TP53-MUT. Pt characteristics are outlined in Table 1A. All pts were treated with low intensity Rx and were divided into the following groups: DAC10 [n=34, 26%]; 5-day decitabine, or 7-day azacytidine (DAC5) [n=39, 30%]; or cladribine+low dose araC (CLAD/LDAC) [n=58, 44%]. Response rates and OS by Rx and TP53-MUT status are summarized in Table 1B. While there was no significant difference in response rates or OS by TP53-MUT status within any of the treatment approaches, there was a trend for inferior response rates and OS among pts with TP53-MUT who received either DAC-5 or CLAD/LDAC ; this was not seen in pts receiving DAC10. Conclusions: The presence of a TP53-MUT was associated with a nonsignificant trend towards inferior outcomes among pts receiving DAC5 or CLAD/LDAC, but not among those receiving DAC10. Comparing across groups, the CLAD/LDAC combination was associated with the longest OS, and DAC10 was associated with superior outcomes compared to DAC5, in TP53-MUT cohort. [Table: see text]
Tyrosine kinase domain mutations of &lt;em&gt;EGFR&lt;/em&gt; gene in head and neck squamous cell carcinoma (2017)

Higher frequency of EGFR-TK domain mutations together with the presence of the T790M mutation suggests that identification of these mutations might streamline the therapy and provide a better prognosis in HNSCC cases.
Speech Recognition for Illiterate Access to Information and Technology (2006)

In rural Tamil Nadu and other predominantly illiterate communities throughout the world, computers and technology are currently inaccessible without the help of a literate mediator. Speech recognition has often been suggested as a key to universal access, but success stories of speech-driven interfaces for illiterate end users are few and far between. The challenges of dialectal variation, multilingualism, cultural barriers, choice of appropriate content, and, most importantly, the prohibitive expense of creating the necessary linguistic resources for effective speech recognition are intractable using traditional techniques. This paper presents an inexpensive approach for gathering the linguistic resources needed to power a simple spoken dialog system. In our approach, data collection is integrated into dialog design: Users of a given village are recorded during interactions, and their speech semi-automatically integrated into the acoustic models for that village, thus generating the linguistic resources needed for automatic recognition of their speech. Our design is multi-modal, scalable, and modifiable. It is the result of an international, cross-disciplinary collaboration between researchers and NGO workers who serve the rural poor in Tamil Nadu. Our groundwork includes user studies, stakeholder interviews and field recordings of literate and illiterate agricultural workers in three districts of Tamil Nadu over the summer and fall of 2005. Automatic speech recognition experiments simulating the spoken dialog systems' performance during initialization and gradual integration of acoustic data informed the holistic structure of the design. Our research addresses the unique social and economic challenges of the developing world by relying on modifiable and highly transparent software and hardware, by building on locally available resources, and by emphasizing community operation and ownership through training and education
Head and neck cancer subtypes with biological and clinical relevance: Meta-analysis of gene-expression data (2015)

Head and neck squamous cell carcinoma (HNSCC) is a disease with heterogeneous clinical behavior and response to therapies. Despite the introduction of multimodality treatment, 40-50% of patients with advanced disease recur. Therefore, there is an urgent need to improve the classification beyond the current parameters in clinical use to better stratify patients and the therapeutic approaches. Following a meta-analysis approach we built a large training set to whom we applied a Disease-Specific Genomic Analysis (DSGA) to identify the disease component embedded into the tumor data. Eleven independent microarray datasets were used as validation sets. Six different HNSCC subtypes that summarize the aberrant alterations occurring during tumor progression were identified. Based on their main biological characteristics and de-regulated signaling pathways, the subtypes were designed as immunoreactive, inflammatory, human papilloma virus (HPV)-like, classical, hypoxia associated, and mesenchymal. Our findings highlighted a more aggressive behavior for mesenchymal and hypoxia-associated subtypes. The Genomics Drug Sensitivity Project was used to identify potential associations with drug sensitivity and significant differences were observed among the six subtypes. To conclude, we report a robust molecularly defined subtype classification in HNSCC that can improve patient selection and pave the way to the development of appropriate therapeutic strategies.
[Gradually improved long-term survival in diabetes. Long disease duration can provide information about protective possibilities]. (2005)

Studies on patients with long-term diabetes survival without severe complications can give information about protective factors. Therefore, the present study aims to describe the long-term survival of patients with diabetes during successive periods following the introduction of insulin therapy in 1923. After registration in 1973 of the first local diabetic patient in Jönköping with a fifty-year survival, this group has successively increased. Of those who were diagnosed during the period 1940 through 1949 there was a fifty-year survival in about one third. The successively better survival emphasises the importance of therapeutic progress. The study found no difference in diabetes control between those surviving 50 years and those with an age-matched group with a survival of 15 years. The insulin dose tended to decrease after 30 years duration. Peripheral vibration sensibility as well as renal function deteriorated by longer duration. The serum ratio of HDL-cholesterol to triglycerides increased. The frequency of glaucoma, cataract, and a history of myocardial infarction increased. In spite of long duration, one third of the sample had escaped serious retinopathy.
Label-free chip-based evanescent light scattering super-resolution and\n superior-contrast optical microscopy (cELS) (2021)

Chip-based Evanescent Light Scattering (cELS) utilizes the multiple modes of a high-index contrast optical waveguide for near-field illumination of unlabeled samples, thereby repositioning the highest spatial frequencies of the sample into the far-field. The multiple modes scattering off the sample with different phase differences is engineered to have random spatial distributions within the integration time of the camera, mitigating the coherent speckle noise. This enables label-free superior-contrast imaging of weakly scattering nanosized specimens such as extra-cellular vesicles (EVs) and liposomes, dynamics of living HeLa cells etc. The article explains and validates experimentally the physics behind cELS by demonstrating a multi-moded straight waveguide as a partially coherent light source. For isotropic super-resolution, spatially incoherent light engineered via multiple-arms waveguide chip and intensity-fluctuation based algorithms are used. The proof-of-concept results are demonstrated on 100 nm polystyrene beads and resolution improvement of close to 2X is shown. cELS also realizes (2-10)X more contrast as opposed to conventional imaging techniques. In addition, cELS platform is miniaturized and enables large field-of-view imaging compared to state of the art label-free techniques. cELS holds a potential for label-free super-resolution imaging of nanosized biological specimens at high-throughput.
Malignant glioma subset from actuate 1801: Phase I/II study of 9-ING-41, GSK-3β inhibitor, monotherapy or combined with chemotherapy for refractory malignancies (2022)

9-ING-41 plus/minus lomustine is safe and warrants further study in glioma patients.
Supplementary Figure 3 from Inflammation-Induced NFATc1–STAT3 Transcription Complex Promotes Pancreatic Cancer Initiation by &lt;i&gt;Kras&lt;/i&gt;&lt;sup&gt;G12D&lt;/sup&gt; (2023)

&lt;p&gt;PDF file 788K, Supplementary Figure 3 refers to Figure 3 and shows STAT3 and NFATc1 expression levels in human and murine pancreatic cancer cell lines as well as NFATc1-dependent STAT3 expression&lt;/p&gt;
Design for manufacture with unknown tolerances (2011)

Several methods have been demonstrated for desensitization of a lens design to manufacturing errors with the result of increased as-built performance at the expense of a slightly reduced nominal performance. A recent study demonstrated a targeted desensitization method tuned for the most sensitive lens parameters can greatly increase yield for a known set of manufacturing tolerances. The effectiveness of such a targeted desensitization relies on two key pieces of information; lens sensitivities and manufacturing tolerance distributions. Targeted desensitization to known and unknown manufacturing tolerances is examined with an example demonstrating the impact of designing to unknown, bounded manufacturing tolerance distributions.
Repeated-Dose Toxicity, Biodistribution, and Shedding Assessments With a ChAd155 Respiratory Syncytial Virus Vaccine Candidate Evaluated in Rabbits and Rats (2022)

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections (LRTI) in infants, and toddlers and vaccines are not yet available. A pediatric RSV vaccine (ChAd155-RSV) is being developed to protect infants against RSV disease. The ChAd155-RSV vaccine consists of a recombinant replication-deficient chimpanzee-derived adenovirus (ChAd) group C vector engineered to express the RSV antigens F, N, and M2-1. The local and systemic effects of three bi-weekly intramuscular injections of the ChAd155-RSV vaccine was tested in a repeated-dose toxicity study in rabbits. After three intramuscular doses, the ChAd155-RSV vaccine was considered well-tolerated. Changes due to the vaccine-elicited inflammatory reaction/immune response were observed along with transient decreases in platelet count without physiological consequences, already reported for other adenovirus-based vaccines. In addition, the biodistribution and shedding of ChAd155-RSV were also characterized in two studies in rats. The distribution and persistence of the ChAd155-RSV vaccine candidate was consistent with other similar adenovector-based vaccines, with quantifiable levels of ChAd155-RSV observed at the injection site (muscle) and the draining lymph nodes up to 69 days post administration. The shedding results demonstrated that ChAd155-RSV was generally not detectable in any secretions or excreta samples. In conclusion, the ChAd155-RSV vaccine was well-tolerated locally and systemically.
Chemical Synthesis of Ozone, Isotopic Labeling, and Redistribution (1998)

Ozone is formed in good yield by reacting O2+ salts with water in HF at −78 °C. With isotopically labeled water 17O−16O−16O and 18O−16O−16O can be prepared, and other isotopomers could be made by starting with 17O2+ and 18O2+ precursors. 17O NMR spectroscopy and IR matrix spectroscopy are used for detection and decay of the isotopomers. The 17O or 18O label at the terminal position remains at −78 °C, but at higher temperatures scrambling of the atoms is observed. Under strict monomolecular conditions no scrambling is observed till 450 °C, however. Irradiation of ozone in a 15K argon matrix with λ = 254 nm affords scrambling of the label and formation of oxygen. Irradiation with λ > 420 nm initiates only scrambling with little decay. The possible mechanisms of the atomic scrambling are discussed.
Identifying the spectroscopic modes of multiferroic BiFeO<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:msub><mml:mrow/><mml:mn>3</mml:mn></mml:msub></mml:math> (2012)

We have identified the modes of multiferroic BiFeO${}_{3}$ measured by THz and Raman spectroscopies. Excellent agreement with the observed peaks is obtained by including the effects of easy-axis anisotropy along the direction of the electric polarization. By distorting the cycloidal spin state, anisotropy splits the ${\ensuremath{\Psi}}_{\ifmmode\pm\else\textpm\fi{}1}$ mode into peaks at 20 and 21.5 cm${}^{\ensuremath{-}1}$ and activates the lower ${\ensuremath{\Phi}}_{\ifmmode\pm\else\textpm\fi{}2}$ mode at 27 cm${}^{\ensuremath{-}1}$ ($T=200$ K). An electromagnon is identified with the upper ${\ensuremath{\Psi}}_{\ifmmode\pm\else\textpm\fi{}1}$ mode at 21.5 cm${}^{\ensuremath{-}1}$. Our results also explain recent inelastic neutron-scattering measurements.
Optimizing the sensitivity of high repetition rate broadband transient optical spectroscopy with modified shot-to-shot detection (2023)

A major limitation of transient optical spectroscopy is that relatively high laser fluences are required to enable broadband, multichannel detection with acceptable signal-to-noise levels. Under typical experimental conditions, many condensed phase and nanoscale materials exhibit fluence-dependent dynamics, including higher order effects such as carrier-carrier annihilation. With the proliferation of commercial laser systems, offering both high repetition rates and high pulse energies, have come new opportunities for high sensitivity pump-probe measurements at low pump fluences. However, experimental considerations needed to fully leverage the statistical advantage of these laser systems have not been fully described. Here, we demonstrate a high repetition rate, broadband transient spectrometer capable of multichannel shot-to-shot detection at 90 kHz. Importantly, we find that several high-speed cameras exhibit a time-domain fixed pattern noise resulting from interleaved analog-to-digital converters, which is particularly detrimental to the conventional "ON/OFF" modulation scheme used in pump-probe spectroscopy. Using a modified modulation and data processing scheme, we achieve a noise level of 10-5 in 4 s for differential transmission, an order of magnitude lower than for commercial 1 kHz transient spectrometers for the same acquisition time. We leverage the high sensitivity of this system to measure the differential transmission of monolayer graphene at low pump fluence. We show that signals on the order of 10-6 OD can be measured, enabling a new data acquisition regime for low-dimensional materials.
Numerical evaluation of RF gas ionization effects in micro-and nano-scale devices (2012)

Micro- and nano-scale gaps are likely to occur in miniaturized and high frequency devices. Large electric fields (~10s V/μm) may result in such gaps even for relatively small voltages commonly found in existing electronics. These strong fields can potentially induce gas discharge, which may lead to performance degradation or even device failure. Gas discharge is due to generation and movement of charged species as a result of impact ionization, secondary electron emission, and field emission phenomena. In this paper, the importance of field emission in gas discharge in small gaps for both DC and RF regimes is investigated by using a numerical-based comparison technique.
Hybrid nanocapsules for <i>in situ</i> TEM imaging of gas evolution reactions in confined liquids (2020)

Liquid cell transmission electron microscopy (TEM) enables the direct observation of dynamic physical and chemical processes in liquids at the nanoscale. Quantitative investigations into reactions with fast kinetics and/or multiple reagents will benefit from further advances in liquid cell design that facilitate rapid in situ mixing and precise control over reagent volumes and concentrations. This work reports the development of inorganic-organic nanocapsules for high-resolution TEM imaging of nanoscale reactions in liquids with well-defined zeptoliter volumes. These hybrid nanocapsules, with 48 nm average diameter, consist of a thin layer of gold coating a lipid vesicle. As a model reaction, the nucleation, growth, and diffusion of nanobubbles generated by the radiolysis of water is investigated inside the nanocapsules. When the nanobubbles are sufficiently small (10-25 nm diameter), they are mobile in the nanocapsules, but their movement deviates from Brownian motion, which may result from geometric confinement by the nanocapsules. Gases and fluids can be transported between two nanocapsules when they fuse, demonstrating in situ mixing without using complex microfluidic schemes. The ability to synthesize nanocapsules with controlled sizes and to monitor dynamics simultaneously inside multiple nanocapsules provides opportunities to investigate nanoscale processes such as single nanoparticle synthesis in confined volumes and biological processes such as biomineralization and membrane dynamics.
A simple colorimetric method for the quality control of 1-alkyl-3-methylimidazolium ionic liquid precursors (2001)

A simple colorimetric method to monitor the production of ionic liquid precursors is developed, which is based on the determination of 1-methylimidazole with copper(II) chloride. The synthesis of 1-ethyl-3-methylimidazolium chloride, an industrially important ionic liquid precursor, can be followed and the purity of the final product can be readily assessed in a quick and convenient manner.
Gold Nanocomposite Bioink for Printing 3D Cardiac Constructs (2017)

Bioprinting is the most convenient microfabrication method to create biomimetic three-dimensional (3D) cardiac tissue constructs, which can be used to regenerate damaged tissue and provide platforms for drug screening. However, existing bioinks, which are usually composed of polymeric biomaterials, are poorly conductive and delay efficient electrical coupling between adjacent cardiac cells. To solve this problem, we developed a gold nanorod (GNR) incorporated gelatin methacryloyl (GelMA)-based bioink for printing 3D functional cardiac tissue constructs. The GNR concentration was adjusted to create a proper microenvironment for the spreading and organization of cardiac cells. At optimized concentration of GNR, the nanocomposite bioink had a low viscosity, similar to pristine inks, which allowed for the easy integration of cells at high densities. As a result, rapid deposition of cell-laden fibers at a high resolution was possible, while reducing shear stress on the encapsulated cells. In the printed GNR constructs, cardiac cells showed improved cell adhesion and organization when compared to the constructs without GNRs. Furthermore, the incorporated GNRs bridged the electrically resistant pore walls of polymers, improved the cell-to-cell coupling, and promoted synchronized contraction of the bioprinted constructs. Given its advantageous properties, this gold nanocomposite bioink may find wide application in cardiac tissue engineering.
Directions for future research (2010)

Scientific and clinical questions are usually answered partially and in increments. Most of the questions posed by Joseph Sheldon in 1935 and at the First International Conference on Hemochromatosis in 1987 have been answered. Since the discovery of HFE in 1996, there has been an explosion of research interest and reports related to iron biology and diseases of iron homeostasis. Some important “unknowns” presented in the conclusion of a major 2000 text devoted to hemochromatosis have been resolved. This section presents some of the important old and new questions for which answers are needed and changes in medical care delivery are predicted. These topics of interest include the biology and genetics of iron homeostasis and iron overload, hemochromatosis and iron overload screening, advances in diagnosis, complications of iron overload, and improvements in management.
Methods of measuring the electric-field-dependent absorbtion coefficient in quantum confined structures (2002)

A review of methods measuring the electric-field-dependent absorption coefficient in quantum confined structures is presented. The methods proposed are based on an approximate modeling of a thin film structure which takes into account the reflections at the air-semiconductor interfaces and interference effects within the structure. It is shown that determination of the absorption coefficient from the measured photocurrent and transmitted power is the most robust against measurement errors and easiest to implement for complete modulator structures.
Artificial intelligence enables comprehensive genome interpretation and nomination of candidate diagnoses for rare genetic diseases (2021)

GEM enabled diagnostic interpretation inclusive of all variant types through automated nomination of a very short list of candidate genes and disorders for final review and reporting. In combination with deep phenotyping by CNLP, GEM enables substantial automation of genetic disease diagnosis, potentially decreasing cost and expediting case review.
Discovery of Spirofused Piperazine and Diazepane Amides as Selective Histamine-3 Antagonists with in Vivo Efficacy in a Mouse Model of Cognition (2014)

A new series of potent and selective histamine-3 receptor (H3R) antagonists was identified on the basis of an azaspiro[2.5]octane carboxamide scaffold. Many scaffold modifications were largely tolerated, resulting in nanomolar-potent compounds in the H3R functional assay. Exemplar compound 6s demonstrated a selective profile against a panel of 144 secondary pharmacological receptors, with activity at only σ2 (62% at 10 μM). Compound 6s demonstrated free-plasma exposures above the IC50 (∼50×) with a brain-to-plasma ratio of ∼3 following intravenous dosing in mice. At three doses tested in the mouse novel object recognition model (1, 3, and 10 mg/kg s.c.), 6s demonstrated a statistically significant response compared with the control group. This series represents a new scaffold of H3 receptor antagonists that demonstrates in vivo exposure and efficacy in an animal model of cognition.
Light absorption (optical density) of the safranin O-stained epiphyseal cartilage. (2015)

&lt;p&gt;Light absorption (optical density) of the safranin O-stained epiphyseal cartilage.&lt;/p&gt;