gebhart/patrepeval huggingface dataset:
Evidence-Based Deprescribing of Statins in Patients With Advanced Illness (2015)

Several observational studies have demonstrated that statins continue to be prescribed for patients with limited life expectancy. In one study, 2 up to 62% of patients with cancer and a poor prognosis continued to receive statins, often for primary prevention of cardiovascular disease. In another trial, 3 the time to stopping treatment with a statin was similar in patients with cancer and in those without cancer, and more than 31% of patients with cancer filled a statin prescription within 30 days of death. Patients with other life-limiting illness, such as advanced dementia, also continued to receive statins even at the end of life. 4 Why are statins continued until the end of life? This is a complex multifaceted issue. Stopping statin therapy in the case of limited life expectancy has been advocated as a relatively straightforward decision; a recommendation of the Choosing Wisely campaign advises not to start lipid-lowering medications in patients with limited life expectancy. 5 However, at present, little is known about the barriers faced by clinicians when stopping statin treatment in patients with limited life expectancy. There may be continued uncertainty on the part of clinicians about the benefits afforded by continuing the treatment, particularly if a patient has been receiving the medication for a long time without adverse effects. Furthermore, clinicians and patients may be uncertain about the benefits and harms of discontinuing the therapy. In this issue of JAMA Internal Medicine, Kutner and colleagues 1 present the results of its first multicenter study: a pragmatic randomized trial of statin therapy discontinuation in patients with advanced disease and limited prognosis. This study suggests that stopping statin treatment at the end of life may be safe and is potentially associated with improved quality of life and reduced cost. The importance of these results cannot be overstated; clinicians wishing to recommend discontinuing the treatment in patients with advanced disease and limited life expectancy now have an evidence base to inform their decision making. Indeed, patients and their caregivers can now be advised that both withdrawing and continuing statin therapy are reasonable alternatives in advanced illness and in the absence of recent cardiovascular events. Will this study provide the evidence needed to help clinicians deprescribe statin treatment? Kutner et al 1 suggest that
MP59-17 A MODEL OF HUMAN PENILE TRANSPLANTATION TO INVESTIGATE THE EFFECTS AND PATHOPHYSIOLOGY OF REJECTION AND CYCLOSPORIN A TREATMENT ON ERECTILE FUNCTION (2016)

The main goal in treatment of patients with Mayer-Rokitansky-K uster-Hauser syndrome (vaginal agenesis) is creation of a neovagina that will satisfy patient's desire. We evaluated sexual and psychosocial outcome after sigmoid vaginoplasty due to vaginal agenesis.
Phase-contrast tomography at the nanoscale using hard x rays (2010)

Synchrotron-based full-field tomographic microscopy established itself as a tool for noninvasive investigations. Many beamlines worldwide routinely achieve micrometer spatial resolution while the isotropic 100-nm barrier is reached and trespassed only by few instruments, mainly in the soft x-ray regime. We present an x-ray, full-field microscope with tomographic capabilities operating at 10 keV and with an isotropic resolution of 144 nm. Custom-designed optical components allow for ideal, aperture-matched sample illumination and very sensitive phase contrast imaging. We show here that the instrument has been successfully used for the nondestructive, volumetric investigation of single cells.
Reduction of interpolation artifacts introduced by moving histogram equalization (MHE) in digital on-line portal images (1993)

Digital on-line portal imaging provides almost real time images of patients undergoing radiation treatments, and is used to verify treatment field size and shape, and to achieve greater set-up and treatment accuracy. A major problem with this new modality is the lack of contrast of anatomical structures due to the relatively small differences in attenuation coefficients of bone and soft tissue, and the large amount of scatter at megavoltage photon energies. One solution to this problem is to process the images using adaptive contrast enhancement techniques, one example of which is known as moving histogram equalization (MHE). A disadvantage of MHE is that artifacts often appear in the enhanced image, especially in regions of relative uniformity. A technique has been developed to remove these artifacts while retaining the high contrast of the enhanced image using matched Fourier domain filtering techniques. The artifact reduction factor is found to be about 0.6 for a variety of on-line portal images.
A family of hybrid neural networks (2002)

The focus of this study is on a family of hybrid architectures for feed-forward multi-layer neural networks and issues that arise in their design. The main objective in the design of this family has been to reduce the complexity of hardware, and hence make possible the implementation of larger networks for practical applications, by two main ideas: trading time for circuit complexity by a multiplexing scheme and a modular characteristic that allows multi-chip realizations without a prohibitive number of interconnections. In this paper, we propose to bring the various forms of this architecture together, which are at this time scattered in the literature. After presenting the main points in its operation, we will proceed to permutations and trade-offs, some of which have not been published in accessible literature so far. We start with the introduction of the basic architecture. We then present modifications and discuss some I/O issues. Matching neural transfer characteristics is important to the performance of the system and we address this problem with a set of second order improvements. Another version of the architecture, with external weight memory, is introduced which allows interaction with a host computer, and finally, a pipelined version of the architecture is presented that improves system speed with a small increment in overall complexity.
Alarmin Function of Galectin-9 in Murine Respiratory Tularemia (2015)

Sepsis is a complex immune disorder that is characterized by systemic hyperinflammation. Alarmins, which are multifunctional endogenous factors, have been implicated in exacerbation of inflammation in many immune disorders including sepsis. Here we show that Galectin-9, a host endogenous β-galactoside binding lectin, functions as an alarmin capable of mediating inflammatory response during sepsis resulting from pulmonary infection with Francisella novicida, a Gram negative bacterial pathogen. Our results show that this galectin is upregulated and is likely released during tissue damage in the lungs of F. novicida infected septic mice. In vitro, purified recombinant galectin-9 exacerbated F. novicida-induced production of the inflammatory mediators by macrophages and neutrophils. Concomitantly, Galectin-9 deficient (Gal-9-/-) mice exhibited improved lung pathology, reduced cell death and reduced leukocyte infiltration, particularly neutrophils, in their lungs. This positively correlated with overall improved survival of F. novicida infected Gal-9-/- mice as compared to their wild-type counterparts. Collectively, these findings suggest that galectin-9 functions as a novel alarmin by augmenting the inflammatory response in sepsis development during pulmonary F. novicida infection.
Characterization of polycrystalline 3C-SiC films deposited from the precursors 1,3-disilabutane and dichlorosilane (2008)

Polycrystalline 3C-SiC thin films are deposited via low pressure chemical vapor deposition from the precursors 1,3-disilabutane (DSB) and dichlorosilane (DCS). Elemental composition, microstructure, surface morphology, and residual stress are characterized as functions of DCS flow rate fraction. Elemental composition varies linearly with DCS fraction, while microstructure changes drastically with slight changes in DCS fraction. Residual stress varies from 1.2GPa tensile to 240MPa tensile, and the causes of which are traced to variations in elemental composition and grain size. A model of residual stress accounting for the effects of elemental composition and grain size on intrinsic stress is developed and found to be in reasonable agreement with experimental data.
Synthetic Control of Manganese Birnessite: Impact of Crystallite Size on Li, Na, and Mg Based Electrochemistry (2017)

Manganese oxide materials are desirable cathode materials due to their low cost and environmentally benign character. Specifically, 2-D layered birnessite (R y MnO 2 ·xH 2 O, R = monovalent or divalent metal ions) materials are conceptually appealing because of their excellent ion-exchange properties. Edge-sharing MnO 6 octahedra constitute the MnO 2 layers where the interlayer spacing of 7 Å is occupied by metal ions and water molecules. Herein, we designed a study of a Mg cation containing birnessite with different crystallite sizes synthesized through a room temperature precipitation and ion exchange reaction, and characterized to determine structure and magnesium content. Electrochemical behavior was tested in lithium ion, sodium ion and magnesium ion based electrolytes, where the influence of crystallite size on electrochemical activity of Mg-birnessite was evaluated. Results and implications for future materials design will be discussed.
Polar effects in free-radical reactions. Rate constants in phenylation and new methods of selective alkylation of heteroaromatic bases (1986)

The rate constants for the addition of the phenyl radical to protonated and unprotonated 4-substituted pyridines have been determined by competition with chlorine abstraction from CC14. The constants range from 2 X 105 to 6 X 106M-1 s-1depending on the substituent and on the degree of protonation. The phenyl radical shows a clear-cut nucleophilic character. On the basis of these rate constants, the use of phenyl radical from diazonium salt or benzoyl peroxide to generate alkyl radicals by iodine or hydrogen abstraction has been developed as a general procedure for the alkylation of heteroaromatic bases. This reaction is characterized by high yields and selectivities. © 1986, American Chemical Society. All rights reserved.
Nanodelivery systems for cutaneous melanoma treatment (2023)

Cutaneous melanoma (CM) is a multifactorial disease whose treatment still presents challenges: the rapid progression to advanced CM, which leads to frequent recurrences even after surgical excision and, notably, the low response rates and resistance to the available therapies, particularly in the case of unresectable metastatic CM. Thereby, alternative innovative therapeutic approaches for CM continue to be searched. In this review we discuss relevant preclinical research studies, and provide a broad-brush analysis of patents and clinical trials which involve the application of nanotechnology-based delivery systems in CM therapy. Nanodelivery systems have been developed for the delivery of anticancer biomolecules to CM, which can be administered by different routes. Overall, nanosystems could promote technological advances in several therapeutic modalities and can be used in combinatorial therapies. Nevertheless, the results of these preclinical studies have not been translated to clinical applications. Thus, concerted and collaborative research studies involving basic, applied, translational, and clinical scientists need to be performed to allow the development of effective and safe nanomedicines to treat CM.
Construction of the SHF Test Apparatus to Measure the Partial Discharge Current Waveforms in the Practical Operation Conditions of Power Transformer and Application to Influence of BTA Addition (2018)

Insulation diagnosis and partial discharge (PD) test have been performed from the viewpoint of operational reliability and quality evaluation of high-voltage electrical power apparatus. The Ultra high frequency (UHF) method that measures the PD-emitted electromagnetic (EM) waves with UHF band (0.3-3 GHz) components is known as one of powerful methods of insulation diagnosis based on PD detection for highvoltage electrical power apparatus. To improve the UHF method, accurate measurement of PD current pulse is quite important because the PD current is a radiation source of the EM wave. Therefore, we have developed the SHF_PDPW (super high frequency wideband PD current pulse waveform measurement) system that enables us to obtain accurately waveforms up to SHF band (3-30 GHz). Using this system, we have investigated PD characteristics such as PD current pulse waveforms in mineral oil used as insulation oil for transformer. As a result, this system could observe the PD phenomena which were a few tens picoseconds order rise time, i.e. undetectable ones in the conventional measurement band. It is necessary to investigate the insulation oil considering practical operation conditions such as degassing, oil temperature change, generation of the combustible gas by discharge and heating oil, addition of additives like 1,2,3-benzotriazole (BTA) and so on, in order to improve the operation method and the reliability of it. In this study, we constructed the new experimental system which could investigate PD properties under the practical conditions of the power transformer. Then, as a first step, we investigated influence of BTA additive on PD characteristics of insulation oil measured by the SHF-PDPW system. BTA has been widely used in transformer oil in Japan. The BTA addition was specified in the Japanese standard (JIS C 2320) in 1988 in order to decrease electrostatic charging. As a result, it could be confirmed that the usefulness of developed experimental system and the influence of BTA additive on PD characteristics.
An approved in vitro approach to preclinical safety and efficacy evaluation of engineered T cell receptor anti-CD3 bispecific (ImmTAC) molecules (2018)

Robust preclinical testing is essential to predict clinical safety and efficacy and provide data to determine safe dose for first-in-man studies. There are a growing number of examples where the preclinical development of drugs failed to adequately predict clinical adverse events in part due to their assessment with inappropriate preclinical models. Preclinical investigations of T cell receptor (TCR)-based immunotherapies prove particularly challenging as these biologics are human-specific and thus the conventional testing in animal models is inadequate. As these molecules harness the full force of the immune system, and demonstrate tremendous potency, we set out to design a preclinical package that would ensure adequate evaluation of these therapeutics. Immune Mobilising Monoclonal TCR Against Cancer (ImmTAC) molecules are bi-specific biologics formed of an affinity-enhanced TCR fused to an anti-CD3 effector function. ImmTAC molecules are designed to activate human T lymphocytes and target peptides within the context of a human leukocyte antigen (HLA), thus require an intact human immune system and peptidome for suitable preclinical screening. Here we draw upon the preclinical testing of four ImmTAC molecules, including IMCgp100, the first ImmTAC molecule to reach the clinic, to present our comprehensive, informative and robust approach to in vitro preclinical efficacy and safety screening. This package comprises a broad range of cellular and molecular assays using human tissues and cultured cells to test efficacy, safety and specificity, and hence predict human responses in clinical trials. We propose that this entirely in vitro package offers a potential model to be applied to screening other TCR-based biologics.
Expression of Anti-Müllerian Hormone during Normal and Pathological Gonadal Development: Association with Differentiation of Sertoli and Granulosa Cells1 (1999)

The ontogeny of expression of anti-Müllerian hormone (AMH) was examined by immunohistochemistry in 135 human gonadal tissue specimens of various developmental age, ranging from 6 weeks of fetal development to 38 yr of postnatal age. The series included specimens from normal testes and ovaries and from individuals either with pathological conditions affecting gonadal development or with idiopathic infertility manifested as azoospermia or severe oligozoospermia. AMH expression was found only in Sertoli and granulosa cells. A 6-week-old fetal testis at the indifferent gonad stage did not yet express AMH. The protein was first visible at 8.5 weeks of development, when sex cords have not yet been formed. Afterward, a majority of testicular specimens, including those from pathological conditions, strongly expressed AMH through fetal development and childhood until puberty. Markedly prolonged expression of AMH was observed in a 20-yr-old 46,XY female with androgen insensitivity syndrome, who retained prepubertal testicular morphology. In normal testes, the switch-off of AMH expression was usually associated with the appearance of primary spermatocytes, suggesting that their presence had an inhibitory effect on AMH. However, in adolescent boys lacking germ cells because of cancer treatment and in a majority of infertile adult men with idiopathic germ cell aplasia, AMH expression was also down-regulated despite the complete lack of spermatogenesis. The decrease in AMH expression thus reflects the terminal differentiation of Sertoli cells and is probably only partially dependent upon a regulatory factor associated with the onset of meiosis. In fetal ovaries, AMH was first detected at 36 weeks gestation in granulosa cells of preantral follicles. Thus, the onset of ovarian expression is at the end of fetal life and not in infancy as previously reported.
Conjunctival dysbiosis in mucosa-associated lymphoid tissue lymphoma (2019)

To investigate the conjunctival microbiota and the association between the development of conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma and dysbiosis, DNA samples were collected from 25 conjunctival MALT lymphoma patients and 25 healthy controls. To compare the microbiota, samples were collected from the following four body locations: conjunctiva, meibomian gland, periocular skin and hand. Extracted DNA was analyzed by 16S rRNA sequences, and libraries were sequenced on an Illumina MiSeq sequencer. The differences in bacteria were characterized by using principal coordinate analysis of metagenomics data, and the differences in bacterial compositions were evaluated by linear discriminant analysis effect size. The conjunctival microbiota of MALT lymphoma patients was compositionally different from that of healthy controls. For the conjunctival MALT lymphoma patients, alterations in the microbial composition were detected, and a remarkable change was detected at the conjunctiva. Detailed analysis showed that a specific population of the microbiota, the genus Delftia, was significantly more abundant in conjunctival MALT lymphoma patients, and the genera Bacteroides and Clostridium were less abundant in the MALT lymphoma patients. A specific microbiota on the ocular surface in conjunctival MALT lymphoma patients was detected, and dysbiosis may play an important role in the pathophysiology of conjunctival MALT lymphoma.
Effect of Synthetic Sialyl 2→1 Sphingosine and Other Glycosylsphingosines on the Structure and Function of the “Glycosphingolipid Signaling Domain (GSD)” in Mouse Melanoma B16 Cells (2000)

Mouse melanoma B16 cells are characterized by a high concentration of GM3 ganglioside, which has been identified as a melanoma-associated antigen and is present as a clustered microdomain organized with major signal transducers, c-Src, small G-protein (Rho A), and focal adhesion kinase (FAK), to form a "glycosphingolipid signaling domain" or "glycosignaling domain" (GSD) separable from cholesterol- and caveolin-enriched microdomain, "caveolae." Cholesterol-binding reagents, filipin and nystatin, disrupt the structure and function of caveolae, but have no effect on GSD function [Iwabuchi, K., et al. (1998) J. Biol. Chem. 273, 33766-33773]. In this study, we searched for compounds which disrupt the structure and function of GSD in B16 cells. Such compounds should have structural features analogous to those of GM3, destroy or reduce clustering of GM3 in GSD, and inhibit GM3-dependent adhesion and signaling. The simplest compound so far found with these properties is sialyl alpha2-->1 sphingosine (Sph). We describe the synthesis of this compound and its analogues, and their effects on GM3 expression pattern and GSD function, in comparison with effects of lyso-GM3 and other lyso compounds, in B16 cells. Incubation of B16 cells with 0.5-10 microM sialyl alpha2-->1 Sph or 1-5 microM lyso-GM3 reduced GM3 clustering and GM3-dependent adhesion, and inhibited adhesion-dependent cellular FAK activity. The c-Src activation response of GSD isolated from B16 cells was inhibited strongly by sialyl alpha2-->1 Sph. Substitution of the Sph amino group with a chloroacetyl or N,N-dimethyl group strongly reduced the inhibitory effect of sialyl alpha2-->1 Sph on GM3-dependent adhesion, FAK, and c-Src response. Other lyso compounds such as lyso-phosphatidylcholine, galactosyl-Sph (psychosine), and lactosyl-Sph at 0.5-10 microM did not show the same effect as sialyl alpha2-->1 Sph. Thus, adhesion coupled with signal transduction, initiated by clusters of GM3 in GSD, is blocked by sialyl alpha2-->1 Sph or lyso-GM3. Analogues with N-substitution of Sph in sialyl alpha2-->1 Sph, other lyso-phospholipids, and galactosyl- or lactosyl-Sph did not block such adhesion, coupled with activation of c-Src and FAK.
Creating Supported Plasma Membrane Bilayers Using Acoustic Pressure (2020)

Model membrane systems are essential tools for the study of biological processes in a simplified setting to reveal the underlying physicochemical principles. As cell-derived membrane systems, giant plasma membrane vesicles (GPMVs) constitute an intermediate model between live cells and fully artificial structures. Certain applications, however, require planar membrane surfaces. Here, we report a new approach for creating supported plasma membrane bilayers (SPMBs) by bursting cell-derived GPMVs using ultrasound within a microfluidic device. We show that the mobility of outer leaflet molecules is preserved in SPMBs, suggesting that they are accessible on the surface of the bilayers. Such model membrane systems are potentially useful in many applications requiring detailed characterization of plasma membrane dynamics.