gebhart/patrepeval huggingface dataset:
Abstract 13139: Single Gene Cardiopoiesis Induced in Human Pluripotent Source (2021)

Introduction: The process of engaging stem cells towards a cardiopoietic (CP) state was established using a protein-based cocktail consisting of multiple growth factors. Although this regenerative enhancement protocol has been successfully tested in advanced clinical trials, it remains resource-intensive. Recent efforts have focused on streamlining cardiopoiesis through a protein-independent alternative that leverages a transfection-based mRNA approach. Microencapsulated modified messenger RNA (M3RNA) was utilized to deliver brachyury (T), an early mesodermal transcription factor to provoke early lineage specification in pluripotent cells. Hypothesis: Transfection of a human pluripotent stem cell source with T induces early expression of CP transcription factors to accelerate cardiac differentiation. Methods: Human pluripotent stem cells were transfected with T and maintained for 14 days. Expression of the cardiopoietic markers MEF2C, GATA4, and Nkx2.5 was analyzed using RT-qPCR, in tandem with MYH6 at days 10 and 20. Differentiation proficiency was independently corroborated by assessing Mef2c and Nkx2.5 expression by IF. Results: Following transfection with T, Nkx2.5, MEF2C and GATA4 were significantly induced at 72h (60-, 20- and 40-fold, respectively, p&lt;0.01 for all 3 markers vs baseline), reflecting timing of differentiation initiation. At 5 days post differentiation, expression of the cardiac-specific Nkx2.5 increased by 5 fold vs control and the cell cycle regulator CHIR (p&lt;0.01), suggesting successful persistent induction of cardiopoeisis. At 10 and 20 days of differentiation, RNA expression of MYH6 was 10-15 times induced in human pluripotent cells transduced with T (p &lt; 0.0001, and p &lt; 0.001 vs control, respectively), compared to 2 times (p&lt;0.05, p&lt;0.01 vs control, respectively) in CHIR treated cohorts. Accordingly, at 42 days post-induction of differentiation, a greater number of cells expressed MLC2V and cTnT (p&lt;1e-05, &lt;1e-07, respectively vs control), driving a robust beating pattern. Conclusion: This study implements a single gene T M3RNA-based approach to readily induce cardiac differentiation from pluripotent sources, exceeding available commercial platforms.
Solid-State Dynamic Nuclear Polarization at 9.4 and 18.8 T from 100 K to Room Temperature (2015)

Efficient dynamic nuclear polarization (DNP) in solids, which enables very high sensitivity NMR experiments, is currently limited to temperatures of around 100 K and below. Here we show how by choosing an adequate solvent, (1)H cross effect DNP enhancements of over 80 can be obtained at 240 K. To achieve this we use the biradical TEKPol dissolved in a glassy phase of ortho-terphenyl (OTP). We study the solvent DNP enhancement of both TEKPol and BDPA in OTP in the range from 100 to 300 K at 9.4 and 18.8 T. Surprisingly, we find that the DNP enhancement decreases only relatively slowly for temperatures below the glass transition of OTP (Tg = 243 K), and (1)H enhancements around 15-20 at ambient temperature can be observed. We use this to monitor molecular dynamic transitions in the pharmaceutically relevant solids Ambroxol and Ibuprofen.
Intracranial Pressure Variation Associated with Changes in End-Tidal CO2 (2006)

Maintaining intracranial pressure (ICP) below 20-25 mmHg is an important clinical goal in the treatment of patients with traumatic brain injury (TBI). It is well known that the partial pressure of arterial CO2 (PaCO2) can affect cerebral blood flow, cerebral blood volume, and therefore ICP. The end-tidal CO2 (ETCO2) is usually monitored by clinicians as a proxy for PaCO2. We show examples where subclinical fluctuations in ETCO2 are associated with clinically significant fluctuations in ICR. We estimated ICP from past and present values of ETCO2 with a linear estimator. The variance of the ICP residuals was 37 percent of the variance of the ICP signal at frequencies above 0.33 mHz. We suggest that a large proportion of clinically significant ICP fluctuations could be eliminated or reduced if the patients ventilation and CO2 levels were more tightly regulated.
P475 Association between disease duration and degree of endoscopic improvement in patients with ulcerative colitis treated with tofacitinib (2020)

Abstract Background Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Efficacy and safety of tofacitinib in patients with UC were evaluated in two Phase 3 induction studies (OCTAVE Induction 1 and 2; NCT01465763, NCT01458951), a 52-week, Phase 3 maintenance study (OCTAVE Sustain, NCT01458574), and an ongoing, open-label, long-term extension study (NCT01470612) [1,2]. Here, we evaluate the association between disease duration and the likelihood of achieving an endoscopic subscore of either 0 or 1 in OCTAVE Induction 1 and 2 and OCTAVE Sustain. Methods The degree of mucosal healing (Mayo endoscopic subscore of 0 or 1) achieved at Week 8 of OCTAVE Induction 1 and 2 (tofacitinib 10 mg twice daily [BID] or placebo) and at Week 52 of OCTAVE Sustain (responders from OCTAVE Induction 1 and 2; tofacitinib 5 or 10 mg BID or placebo) was evaluated in relation to UC disease duration at OCTAVE Induction 1 and 2 baseline (ie prior to study treatment). The association between disease duration category (&amp;lt;3, 3–6 and &amp;gt;6 years) and endoscopic subscore (centrally read) was assessed using the Cochran–Mantel–Haenszel chi-square test. Patients who did not achieve mucosal healing (as observed) were excluded. Results A total of 303/1139 (26.6%) patients achieved mucosal healing at Week 8 of OCTAVE Induction 1 and 2, and 190/593 (32.0%) at Week 52 of OCTAVE Sustain. Of patients who achieved mucosal healing at Week 8 of OCTAVE Induction 1 and 2 (with tofacitinib or placebo), 89 (29.4%), 76 (25.1%) and 138 (45.5%) had baseline disease durations of &amp;lt;3 years, 3–6 years and &amp;gt;6 years, respectively. Overall (among patients who achieved mucosal healing, treated with tofacitinib or placebo), no statistically significant association between disease duration and endoscopic subscore was observed, either at Week 8 of OCTAVE Induction 1 and 2 or at Week 52 of OCTAVE Sustain (chi-squared p = 0.13 and p = 0.23, respectively). In both OCTAVE Induction 1 and 2 and OCTAVE sustain, a numerically higher proportion of patients with shorter disease duration (&amp;lt;3 years) had complete mucosal healing (endoscopic subscore of 0) with tofacitinib vs. patients with longer disease duration (tofacitinib 10 mg BID and/or tofacitinib all groups) (Table). Conclusion Among patients with endoscopic improvement after induction and maintenance therapy with tofacitinib, rates of complete mucosal healing were numerically higher among those with UC for &amp;lt;3 years before starting treatment than among those with a longer disease duration. These analyses are post hoc and limited by the small sample size. References
Virulent Leptospira interrogans Induce Cytotoxic Effects in Human Platelets in vitro Through Direct Interactions (2020)

Leptospirosis is a prevalent zoonotic disease, caused by bacteria of the genus <i>Leptospira</i>. Leptospirosis frequently leads to hemostatic disturbances, and the severe cases are marked by hemorrhages and low platelet number in circulation, which is associated with the patients' poor outcomes. Nevertheless, <i>Leptospira</i>-platelet interactions remain poorly explored. In this study, we performed a series of <i>in vitro</i> experiments evaluating whether leptospires induce human platelet aggregation, activation, and morphological changes. Platelets were incubated with virulent <i>L. interrogans</i> and the platelet outcomes were assessed by aggregometry, flow cytometry, and scanning and transmission electron microscopy. Our results show that leptospires alone do not induce platelet aggregation and activation, and induce platelet cytotoxic effects instead, by clearly inducing platelet disruption and detachment. We show for the first time that virulent leptospires do interact directly with platelets, an event that could trigger pathophysiological effects during the infection. This study might serve as a basis for the development of novel treatments for the disease.
Clinical trial of retinal and choroidal angiography by laser Doppler holography (Conference Presentation) (2020)

Non-invasive, near infrared angiography by high-speed digital holography allows for blood flow imaging and measurement of quantitative hemodynamic parameters in the human eye with an unrivaled temporal resolution. It reveals blood flow contrasts in the retinal and choroidal vasculature and enables vessel type identification. We report the first results of a clinical trial involving laser Doppler holographic monitoring of the eye fundus (IMA-MODE), designed to assess the pathophysiology of a number of ocular and general diseases appearing with age, such as occlusions, hypertension and diabetes, which may affect the ocular circulation, and provoke potentially blinding microvascular damage.
Gap closure in a cold metal halide lamp (2002)

The breakdown of a cold metal halide lamp has been investigated using a two-dimensional, plasma transport model. Images are presented of the electron density during the trigger and sustain voltage pulses. Charging of the sidewalls of the lamp are, found to be important during gap closure.
Vaginal Reconstruction with the Abbè-McIndoe Technique: From Dermal Grafts to Autologous in Vitro Cultured Vaginal Tissue Transplant (2011)

Vaginal agenesis represents the most common anomaly of the lower female genital tract. Surgical treatments have gradually evolved from aggressive procedures to minimally invasive techniques. The Abbè-McIndoe procedure is one of the most frequent surgical procedures used. The original Abbè-McIndoe procedure consisted of the surgical creation of a vagina in between the bladder and the rectum and the successive lining with a dermal graft. In the last decades different authors have introduced several modifications, mostly changing the lining material. Amniotic membranes, inert materials, and oral mucosa have all been used to improve the short- and long-term results. Recently, we have reported the use of autologous in vitro grown vaginal tissue as lining material with highly promising results. In this review, we discuss the improvements achieved using this minimally invasive procedure and discuss the advantages and disadvantages of the different materials.
Spatially Selecting a Single Cell for Lysis Using Light‐Induced Electric Fields (2014)

An optoelectronic tweezing (OET) device, within an integrated microfluidic channel, is used to precisely select single cells for lysis among dense populations. Cells to be lysed are exposed to higher electrical fields than their neighbours by illuminating a photoconductive film underneath them. Using beam spot sizes as low as 2.5 μm, 100% lysis efficiency is reached in <1 min allowing the targeted lysis of cells.
Evidence for Novel Pharmacological Sensitivities of Transient Receptor Potential (TRP) Channels in Schistosoma mansoni (2015)

Schistosomiasis, caused by parasitic flatworms of the genus Schistosoma, is a neglected tropical disease affecting hundreds of millions globally. Praziquantel (PZQ), the only drug currently available for treatment and control, is largely ineffective against juvenile worms, and reports of PZQ resistance lend added urgency to the need for development of new therapeutics. Ion channels, which underlie electrical excitability in cells, are validated targets for many current anthelmintics. Transient receptor potential (TRP) channels are a large family of non-selective cation channels. TRP channels play key roles in sensory transduction and other critical functions, yet the properties of these channels have remained essentially unexplored in parasitic helminths. TRP channels fall into several (7-8) subfamilies, including TRPA and TRPV. Though schistosomes contain genes predicted to encode representatives of most of the TRP channel subfamilies, they do not appear to have genes for any TRPV channels. Nonetheless, we find that the TRPV1-selective activators capsaicin and resiniferatoxin (RTX) induce dramatic hyperactivity in adult worms; capsaicin also increases motility in schistosomula. SB 366719, a highly-selective TRPV1 antagonist, blocks the capsaicin-induced hyperactivity in adults. Mammalian TRPA1 is not activated by capsaicin, yet knockdown of the single predicted TRPA1-like gene (SmTRPA) in S. mansoni effectively abolishes capsaicin-induced responses in adult worms, suggesting that SmTRPA is required for capsaicin sensitivity in these parasites. Based on these results, we hypothesize that some schistosome TRP channels have novel pharmacological sensitivities that can be targeted to disrupt normal parasite neuromuscular function. These results also have implications for understanding the phylogeny of metazoan TRP channels and may help identify novel targets for new or repurposed therapeutics.
“Designer” Cells for Cellular Immunotherapy: Zinc Finger Nuclease (ZFN) Stimulated Targeted Recombination for the Simultaneous Disruption of the Endogenous Glucocorticoid Receptor and Site-Specific Addition of the IL13-Zetakine. (2006)

Abstract Immunotherapy utilizing genetically-modified cytolytic T-lymphocytes (CTL) provides a promising therapeutic approach for treating a variety of diseases, including cancer. We have demonstrated that CTLs encoding a chimeric T-cell receptor (IL13-zetakine), consisting of an extracellular IL-13 domain and a cytoplasmic CD3 domain, can be re-directed to target malignant glioma both in vitro and in animal models. This chimera re-targets the antigen-specific effector functions of modified CTLs to recognize glioblastomas due to the high expression of IL13R in these tumors. However, practical application of this approach is limited by the fact that patients undergoing surgical resection of the tumor often require treatment with glucocorticoids to control the resulting inflammation. Such treatment blocks the activity of the re-directed CTL clones and thus inhibits their therapeutic action. To overcome this limitation and render these tumor-specific CTLs resistant to glucocorticoids we have chosen to employ engineered ZFNs to specifically disrupt the endogenous glucocorticoid receptor (GR) gene. Heterodimeric ZFNs, consisting of the cleavage domain of the restriction enzyme FokI linked to engineered zinc finger DNA-binding domains, can be designed to specifically cleave a predetermined site in the genome. We have shown that these ZFN-induced double strand breaks can promote homologous recombination with high efficiency. In the present study we have investigated the use of ZFNs to simultaneously effect functional inactivation of human GR via specifically targeting the integration of the IL13-zetakine expression cassette into the GR locus itself. We can show that GR-specific ZFNs cleave their intended target sequences with high specificity and efficiency - resulting in the disruption of GR and the creation of glucocorticoid resistant cells. Moreover, we can demonstrate that these ZFNs coupled with an appropriate IL13-zetakine containing donor-DNA molecule can stimulate the integration of this chimeric T-cell receptor directly into the GR locus. Thus, this procedure results in the simultaneous knockout of GR and addition of the IL13-zetakine in a genetically defined manner. These data support the notion that ZFN-modified cells can be engineered to express chimeric antigen receptors from a predetermined genomic locus and may provide a general approach to generating effective cellular immunotherapy strategies.
The resist-core spacer patterning process for fabrication of 2xnm node semiconductor devices (2011)

The spacer patterning process is one of the strongest double patterning technology candidates for fabricating 2xnm node semiconductor devices by ultra-low-k1 lithography. However, a severe problem exists with this process, it has an excessive number of steps, including resist patterning, core film etching, spacer film deposition, spacer film etchback, core film removal, and hard mask patterning steps. We devised a simpler process in which a resist pattern is directly used as the core film pattern and the spacer film is a low-temperature-deposited oxide film that can be fabricated around the resist pattern without damaging the resist material. Thus, this new process, which we call "resist-core" spacer patterning, has significantly fewer patterning steps. When we used the new process to fabricate 2xnm node semiconductor devices with an ArF immersion scanner, two key issues arose. The first issue regarding the controllability of the resist pattern profile, which can directly affect the spacer film pattern profile, was addressed by applying various resist patterning conditions such as resist materials, illumination conditions, and bottom anti-reflecting materials. The second issue, regarding the resist slimming method was addressed by evaluating two alternative techniques, wet slimming and dry slimming.
DynamicME: dynamic simulation and refinement of integrated models of metabolism and protein expression (2019)

Overall, DynamicME provides a novel method for understanding proteome allocation and metabolism under complex and transient environments, and to utilize time-course cell culture data for model-based interpretation or model refinement.
Constraints on the interactions between dark matter and baryons from the x-ray quantum calorimetry (2007)

Although the rocket-based x-ray quantum calorimetry (XQC) experiment was designed for x-ray spectroscopy, the minimal shielding of its calorimeters, its low atmospheric overburden, and its low-threshold detectors make it among the most sensitive instruments for detecting or constraining strong interactions between dark matter particles and baryons. We use Monte Carlo simulations to obtain the precise limits the XQC experiment places on spin-independent interactions between dark matter and baryons, improving upon earlier analytical estimates. We find that the XQC experiment rules out a wide range of nucleon-scattering cross sections centered around 1 b for dark matter particles with masses between 0.01 and 10^5 GeV. Our analysis also provides new constraints on cases where only a fraction of the dark matter strongly interacts with baryons.
Nonlinear Optics with Near-Infrared Excitation Enable Real-Time Quantitative Diagnosis of Human Cervical Cancers (2020)

Histopathologic analysis through biopsy has been one of the most useful methods for the assessment of malignant neoplasms. However, some aspects of the analysis such as invasiveness, evaluation range, and turnaround time from biopsy to report could be improved. Here, we report a novel method for visualizing human cervical tissue three-dimensionally, without biopsy, fixation, or staining, and with sufficient quality for histologic diagnosis. Near-infrared excitation and nonlinear optics were employed to visualize unstained human epithelial tissues of the cervix uteri by constructing images with third-harmonic generation (THG) and second-harmonic generation (SHG). THG images enabled evaluation of nuclear morphology in a quantitative manner with six parameters after image analysis using deep learning. It was also possible to quantitatively assess intraepithelial fibrotic changes based on SHG images and another deep learning analysis. Using each analytical procedure alone, normal and cancerous tissue were classified quantitatively with an AUC ≥0.92. Moreover, a combinatory analysis of THG and SHG images with a machine learning algorithm allowed accurate classification of three-dimensional image files of normal tissue, intraepithelial neoplasia, and invasive carcinoma with a weighted kappa coefficient of 0.86. Our method enables real-time noninvasive diagnosis of cervical lesions, thus constituting a potential tool to dramatically change early detection. SIGNIFICANCE: This study proposes a novel method for diagnosing cancer using nonlinear optics, which enables visualization of histologic features of living tissues without the need for any biopsy or staining dye.
Evaluation of serological lateral flow assays for severe acute respiratory syndrome coronavirus-2 (2021)

Abstract Background COVID-19 has resulted in significant morbidity and mortality worldwide. Lateral flow assays can detect anti-Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) antibodies to monitor transmission. However, standardized evaluation of their accuracy and tools to aid in interpreting results are needed. Methods We evaluated 20 IgG and IgM assays selected from available tests in April 2020. We evaluated the assays’ performance using 56 pre-pandemic negative and 56 SARS-CoV-2-positive plasma samples, collected 10-40 days after symptom onset, confirmed by a molecular test and analyzed by an ultra-sensitive immunoassay. Finally, we developed a user-friendly web app to extrapolate the positive predictive values based on their accuracy and local prevalence. Results Combined IgG+IgM sensitivities ranged from 33.9% to 94.6%, while combined specificities ranged from 92.6% to 100%. The highest sensitivities were detected in Lumiquick for IgG (98.2%), BioHit for both IgM (96.4%), and combined IgG+IgM sensitivity (94.6%). Furthermore, 11 LFAs and 8 LFAs showed perfect specificity for IgG and IgM, respectively, with 15 LFAs showing perfect combined IgG+IgM specificity. Lumiquick had the lowest estimated limit-of-detection (LOD) (0.1 μg/mL), followed by a similar LOD of 1.5 μg/mL for CareHealth, Cellex, KHB, and Vivachek. Conclusion We provide a public resource of the accuracy of select lateral flow assays with potential for home testing. The cost-effectiveness, scalable manufacturing process, and suitability for self-testing makes LFAs an attractive option for monitoring disease prevalence and assessing vaccine responsiveness. Our web tool provides an easy-to-use interface to demonstrate the impact of prevalence and test accuracy on the positive predictive values.
Direct sampling and analysis from solid‐phase extraction cards using an automated liquid extraction surface analysis nanoelectrospray mass spectrometry system (2011)

Direct liquid extraction based surface sampling, a technique previously demonstrated with continuous flow and autonomous pipette liquid microjunction surface sampling probes, has recently been implemented as a liquid extraction surface analysis (LESA) mode on a commercially available chip-based infusion nanoelectrospray ionization (nanoESI) system. In the present paper, the LESA mode was applied to the analysis of 96-well format custom-made solid-phase extraction (SPE) cards, with each well consisting of either a 1 or a 2 mm diameter monolithic hydrophobic stationary phase. These substrate wells were conditioned, loaded with either single or multi-component aqueous mixtures, and read out using the commercial nanoESI system coupled to a hybrid triple quadrupole/linear ion trap mass spectrometer or a linear ion trap mass spectrometer. The extraction conditions, including extraction/nanoESI solvent composition, volume, and dwell times, were optimized in the analysis of targeted compounds. Limit of detection and quantitation as well as analysis reproducibility figures of merit were measured. Calibration data was obtained for propranolol using a deuterated internal standard which demonstrated linearity and reproducibility. A 10× increase in signal and cleanup of micromolar angiotensin II from a concentrated salt solution was demonstrated. In addition, a multicomponent herbicide mixture at ppb concentration levels was analyzed using MS(3) spectra for compound identification in the presence of isobaric interferences.