gebhart/patrepeval huggingface dataset:
Review article: moving towards common therapeutic goals in Crohn's disease and rheumatoid arthritis (2017)

Novel therapeutic strategies in CD based on tight control of objective signs of inflammation are expected to change disease course and patients' lives by halting progression or, ideally, preventing the occurrence of bowel damage. Most of these strategies require validation in prospective studies, whereas several disease-modification trials have addressed these issues in rheumatoid arthritis over the last decade. The recent approval of new drugs in CD such as vedolizumab and ustekinumab should facilitate initiation of disease-modification trials in CD in the near future.
A Bayesian reanalysis of the Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial (2022)

In a Bayesian reanalysis of the STARRT-AKI trial, we found very low probability that an accelerated strategy has clinically important benefits compared with the standard strategy. Patients receiving the accelerated strategy probably have fewer days alive and KRT-free. These findings do not support the adoption of an accelerated strategy of KRT initiation.
Self-Exfoliated Guanidinium-Based Ionic Covalent Organic Nanosheets (iCONs) (2016)

Covalent organic nanosheets (CONs) have emerged as functional two-dimensional materials for versatile applications. Although π-π stacking between layers, hydrolytic instability, possible restacking prevents their exfoliation on to few thin layered CONs from crystalline porous polymers. We anticipated rational designing of a structure by intrinsic ionic linker could be the solution to produce self-exfoliated CONs without external stimuli. In an attempt to address this issue, we have synthesized three self-exfoliated guanidinium halide based ionic covalent organic nanosheets (iCONs) with antimicrobial property. Self-exfoliation phenomenon has been supported by molecular dynamics (MD) simulation as well. Intrinsic ionic guanidinium unit plays the pivotal role for both self-exfoliation and antibacterial property against both Gram-positive and Gram-negative bacteria. Using such iCONs, we have devised a mixed matrix membrane which could be useful for antimicrobial coatings with plausible medical benefits.
ASSOCIATION OF MEAN ARTERIAL PRESSURE, MINIMUM HEMATOCRIT AND MAXIMUM GLUCOSE WITH MORTALITY IN CARDIAC SURGERY (1999)

Introduction: With an aging population in the United States, the number and complexity of coronary artery bypass grafting procedures (CABG) is increasing. Risk stratification schemes have been developed to predict outcome which are predominately based upon unalterable preoperative patient characteristics. [1] The impact of alterable intraoperative physiologic variables upon outcome is less well defined. The use of an intraoperative data acquisition system permits automatic recording of many physiologic variable measured during cardiac surgery. The purpose of this study was to determine if minimum intraoperative hematocrit (MINHCT), maximum glucose concentration (MAXGLC) or mean arterial pressure (MAP) influence in-hospital mortality after CABG. Methods: Outcome data for 2830 patients undergoing CABG surgery at the Duke Heart Center were merged with data from the intraoperative database for analysis. Preoperative risk factors described by Hannan, et al. [1] were used to calculate a predictive probability of death. Because preoperative hypertension (HTN) may influence the intraoperative MAP but is not included as part of the Hannan score, HTN was included as an independent predictor variable for analysis. A query of the intraoperative database yielded values for HCT, GLC and MAP for each patient. MAPALT50, defined as the integrated area below a MAP of 50mmHg at each minute during cardiopulmonary bypass (CPB), provided an index of low MAP. MAPAGE50, defined as the area greater than or equal to a MAP of 50mmHg at each minute during CPB, provided an index of high MAP. Univariate logistic regression was performed on each of the predictor variables to determine association with mortality. Variables found significant (p<0.05) by univariate analysis were tested in a multiple variable model controlling for Hannan score and CPB using backwards stepwise logistic regression. Results: Among the 2830 patients studied, mortality rate was 1.8%. Hannan score was significantly associated with mortality (p=0.0001, c-index=0.696). No significant association was present between mortality and HCT, GLC or MAPALT50 by univariate analysis. HCT and Hannan score covaried (p=0.0001, r=-0.15). MAPAGE50 was significantly associated with mortality by univariate analysis and after controlling for Hannan score but became completely insignificant (p=0.9679) when controlling for CPB time. HTN was an independent predictor of mortality after controlling for Hannan score and CPB duration. Discussion: As expected, Hannan score accurately predicted mortality. HTN proved to be an independent predictor of in-hospital mortality in our patient population. In spite of earlier research which suggests that high MAP during CPB improves outcome, [2] or that lower hematocrit increases mortality, [3] this study finds no evidence to support the hypothesis that MAP less than 50mmHg or lower hematocrit on CPB increases in-hospital mortality.
Progenitor identification and SARS-CoV-2 infection in long-term human distal lung organoid cultures (2020)

The distal lung contains terminal bronchioles and alveoli that facilitate gas exchange and is affected by disorders including interstitial lung disease, cancer, and SARS-CoV-2-associated COVID-19 pneumonia. Investigations of these localized pathologies have been hindered by a lack of 3D in vitro human distal lung culture systems. Further, human distal lung stem cell identification has been impaired by quiescence, anatomic divergence from mouse and lack of lineage tracing and clonogenic culture. Here, we developed robust feeder-free, chemically-defined culture of distal human lung progenitors as organoids derived clonally from single adult human alveolar epithelial type II (AT2) or <i>KRT5</i> <sup>+</sup> basal cells. AT2 organoids exhibited AT1 transdifferentiation potential, while basal cell organoids progressively developed lumens lined by differentiated club and ciliated cells. Organoids consisting solely of club cells were not observed. Upon single cell RNA-sequencing (scRNA-seq), alveolar organoids were composed of proliferative AT2 cells; however, basal organoid <i>KRT5</i> <sup>+</sup> cells contained a distinct <i>ITGA6</i> <sup>+</sup> <i>ITGB4</i> <sup>+</sup> mitotic population whose proliferation segregated to a <i>TNFRSF12A</i> <sup>hi</sup> subfraction. Clonogenic organoid growth was markedly enriched within the TNFRSF12A <sup>hi</sup> subset of FACS-purified ITGA6 <sup>+</sup> ITGB4 <sup>+</sup> basal cells from human lung or derivative organoids. In vivo, TNFRSF12A <sup>+</sup> cells comprised ~10% of KRT5 <sup>+</sup> basal cells and resided in clusters within terminal bronchioles. To model COVID-19 distal lung disease, we everted the polarity of basal and alveolar organoids to rapidly relocate differentiated club and ciliated cells from the organoid lumen to the exterior surface, thus displaying the SARS-CoV-2 receptor ACE2 on the outwardly-facing apical aspect. Accordingly, basal and AT2 apical-out organoids were infected by SARS-CoV-2, identifying club cells as a novel target population. This long-term, feeder-free organoid culture of human distal lung alveolar and basal stem cells, coupled with single cell analysis, identifies unsuspected basal cell functional heterogeneity and exemplifies progenitor identification within a slowly proliferating human tissue. Further, our studies establish a facile in vitro organoid model for human distal lung infectious diseases including COVID-19-associated pneumonia.
Preparation and Reactivity Study of a Versatile Trifluoromethylthiolating Agent: S‐Trifluoromethyl Trifluoromethanesulfonothioate (TTST) (2023)

A novel, air and thermally stable, yet highly reactive trifluoromethylthiolating reagent, CF<sub>3</sub> SO<sub>2</sub> SCF<sub>3</sub> (1), was prepared easily in one step from commercially inexpensive CF<sub>3</sub> SO<sub>2</sub> Na and Tf<sub>2</sub> O. 1 is a highly versatile and atom-efficient reagent that can generate one equivalent of CF<sub>3</sub> S<sup>+</sup> , two equivalents of CF<sub>3</sub> S<sup>-</sup> , or a combination of CF<sub>3</sub> S⋅/CF<sub>3</sub> ⋅ species. Many high-yielding CF<sub>3</sub> S reactions of C, O, S, and N-nucleophiles were achieved, including the simple-step preparations of many reported CF<sub>3</sub> S reagents. 1 delivered a hitherto hard-to-synthesize ArOSCF<sub>3</sub> that was followed by a novel CF<sub>3</sub> S<sup>II</sup> -rearrangement. Through Cu or TDAE/Ph<sub>3</sub> P combinations, 1 generated two equivalents of CF<sub>3</sub> S anion species, and the photo-catalyzed reactions of alkenes with 1 provided CF<sub>3</sub> /CF<sub>3</sub> S-containing products in high atom-efficiency.
Programmed Cell Death as a Mechanism of CD4 and CD8 T Cell Deletion in AIDS: Molecular Control and Effect of Highly Active Anti‐retroviral Therapy (1999)

Infection with human immunodeficiency virus (HIV) results in the progressive destruction of CD4 T lymphocytes, generally associated with progression of the disease. The progressive disappearance of CD4 T lymphocytes leads to the lack of control of HIV replication and to the development of severe immune deficiency responsible for the occurrence of opportunistic infections associated with AIDS. In this review we discuss premature lymphocyte apoptosis in the context of HIV infection as the consequence of the continuous production of viral proteins, leading to an unbalanced immune activation and to the triggering of apoptotic programs. The chronic immune activation induces the continuous expression of death factors which could turn lymphocytes, including CD4 T cells, CD8 CTL or APC, into effectors of apoptosis, leading to the destruction of healthy activated non-infected cells. Thus, programmed cell death would significantly contribute to peripheral T cell depletion in AIDS, particularly if the Th cell renewal is impaired. Under potent anti-retroviral therapies, a complete normalization of lymphocyte apoptosis is observed, concomitant with a partial restoration of the number and the functions of the immune system.
Integrated Inter-Tower Wireless Communications Network for Terrestrial Broadcasting and Multicasting Systems (2021)

This paper describes systems, devices, and methods to implement a bi-directional integrated inter-tower wireless communications network (IITWCN). The described technology can be implemented in combination with the Broadcast Core Network (BCN) in next generation broadcast eco-system and, therefore, support new business cases for broadcast operators such as the delivery of flexible datacasting services or support broadcast or point-to-point Internet services. The introduced bi-directional inter-tower communications network (ITCN) extends the previous unidirectional in-band distribution links (IDL) and adopts the on-channel repeater (OCR) as a simplified backhaul solution in single frequency networks (SFN). The concept of the coordinated ITCN is also presented, aiming at future broadcast Internet services. The ITCN provides a scalable and configurable network solution embedded in a broadcast system, which becomes independent from any non-broadcasting telecommunication infrastructure. The described technology partially relies on the infrastructure of the underlying broadcast/multicast network, using the allocated service channels without requiring additional frequency bands or a separate frequency band. The bi-directional inter-transmitter communication links are therefore referred to as integrated transmission links and the corresponding network as an integrated network.
Long Digital Extensor Tendon Mineralization and Cranial Cruciate Ligament Rupture in a Dog (2014)

Objective To report clinical and histopathologic features of long digital extensor (LDE) tendon mineralization with concurrent cranial cruciate ligament (CCL) rupture in a dog. Study Design Case report. Animal 1.5‐year‐old, male castrated, English bulldog mix weighing 31.5 kg. Methods Pre‐ and postoperative orthogonal radiographs, arthroscopic evaluation, arthrotomy with en bloc surgical excision, and histopathologic analysis of the excised LDE tendon. Results There was radiographic evidence of mineralization in the region of the proximal LDE and stifle instability suggestive of CCL rupture. Arthroscopy, and subsequent arthrotomy, showed complete tearing of the CCL and an intact but grossly thickened LDE. No evidence of avulsion or bony proliferation associated with the LDE was appreciated. Tibial plateau leveling osteotomy (TPLO) and tenectomy of the LDE returned the dog to normal weight‐bearing. No evidence of ectopic mineralization in the affected limb or similar clinical signs in the contralateral limb have been observed in 12 months follow‐up. Conclusions LDE tenectomy followed by stabilization of the stifle by TPLO resulted in a functional outcome. Mineralization without concurrent avulsion of the LDE has not been reported in dogs; however, posterolateral tendon injury in people has been linked to knee instability and cruciate ligament rupture.
Obstetrical Brachial Plexus Palsy (2009)

In this article, the authors review their approach to evaluation, operative management, and reconstructive technique. Brachial plexus injuries in the newborn are usually managed nonoperatively. The timing and indications for primary surgery vary significantly between institutions. The motor examination is used to determine which infants would benefit from operative management. Patients are selected based on established criteria, such as the Toronto Test Score, applied at age 3 months. However, some cases are initially less clear, and we may recommend delaying operative management until age 6 months or as late as age 9 months if the child fails the cookie test. Neuroma excision, sural nerve grafting, and nerve transfers are performed when indicated by clinical motor examination. The use of selective motor nerve transfers, either in combination with nerve grafting or alone, has allowed nerve coaptations to be performed closer to the neuromuscular junction, which may further improve regeneration. Children undergoing primary surgery experience low rates of perioperative morbidity, and they experience gains in motor function until 3 or 4 years postoperatively, at which point recovery stabilizes.
Design of SARS-CoV-2 hFc-Conjugated Receptor-Binding Domain mRNA Vaccine Delivered via Lipid Nanoparticles (2021)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as the causal agent of COVID-19 and stands at the center of the current global human pandemic, with death toll exceeding one million. The urgent need for a vaccine has led to the development of various immunization approaches. mRNA vaccines represent a cell-free, simple, and rapid platform for immunization, and therefore have been employed in recent studies toward the development of a SARS-CoV-2 vaccine. Herein, we present the design of an mRNA vaccine, based on lipid nanoparticles (LNPs)-encapsulated SARS-CoV-2 human Fc-conjugated receptor-binding domain (RBD-hFc). Several ionizable lipids have been evaluated <i>in vivo</i> in a luciferase (luc) mRNA reporter assay, and two leading LNPs formulations have been chosen for the subsequent RBD-hFc mRNA vaccine strategy. Intramuscular administration of LNP RBD-hFc mRNA elicited robust humoral response, a high level of neutralizing antibodies and a Th1-biased cellular response in BALB/c mice. The data in the current study demonstrate the potential of these lipids as promising candidates for LNP-based mRNA vaccines in general and for a COVID19 vaccine in particular.
Shakedown response of conditioned shape memory alloy wire (2008)

A series of experiments is presented examining the thermo-electro-mechanical response of commercially-available, conditioned, shape memory alloy (SMA) wires (Flexinol, from Dynalloy, Corp.) during cyclic thermomechanical loading. A specialized experimental setup enables temperature control via a thermoelectric/heatsink in thermal contact with the wire specimen during various modes of testing. It allows simultaneous measurement of elongation, load, strain and resistivity in a selected gage length. It also allows full-field optical and infrared imaging to be performed during testing. A moderately high transition temperature NiTi-based shape memory wire (90C Flexinol) is characterized first by differential scanning calorimetry and a series of isothermal experiments over a range of temperatures. Subsequent experiments examine the shakedown behavior over a range of dead loading temperature cycles. Results show a significant two-way shape memory effect, suggesting that both residual stresses and locked-in oriented Martensite are considerable in this commercial alloy. Repeatable behavior (little shakedown) is confirmed at relatively low stress levels, but significant evolution in the response (shakedown behavior) exists at higher stress levels during the first several temperature cycles.
General Solid-Phase Synthesis Approach To Prepare Mechanism-Based Aspartyl Protease Inhibitor Libraries. Identification of Potent Cathepsin D Inhibitors (1998)

A general method has been developed for the expedient solid-phase synthesis of aspartyl protease inhibitors that do not incorporate any amino acids. The synthesis approach was designed to allow the introduction of diverse functionality at all four variable sites in inhibitors 1a,b using readily available precursors. Representative, analytically pure inhibitors were obtained in 45−64% overall yields for the 12-step solid-phase synthesis sequence that includes both stereoselective reduction and carbon−carbon bond forming steps. A library of 204 spatially separate compounds was also prepared and screened against cathepsin D and resulted in the identification of a number of potent small molecule inhibitors (Ki = 0.7−3 nM). The described synthesis approach enables the rapid identification of small molecule inhibitors to diverse aspartyl protease targets. The general design principles are also applicable to other enzyme classes.
<title>Application of statistical pattern recognition and image processing in ultrasound tissue characterization</title> (1990)

This paper consists of two parts. The first part considers the limitations imposed by statistical properties of ultrasound images. Through this analysis the minimum detectable tumor size from an ultrasound Bscan using the current state of the art is determined the second part describes an improvement to a successful tissue-characterization algorithm that adds several image processing steps to compute the tissuecharacterization features. The inclusion of such steps will enable the tissue-characterization algorithm to take advantage of visual cues similar to those that a clinician would use to differentiate various organs and segments of the image. This in turn expands the applicability of the present tissue-characterization algorithm from multivariate to multiorgan and multidisease cases.
Analysis and Design of the Protection Scheme for a LVDC Microgrid (2019)

The growing diffusion of renewable energy sources is leading to a considerable revision of the distribution network. In this context, the adoption of direct current distribution grid can bring benefits to the hosting capacity and energy efficiency. However, the protection of such network involves many challenges, especially in case of LVDC microgrids with more than one feeder. The traditional protection schemes used for AC grid are not able to isolate faults and to protect the components of the DC grid. This paper deals with the analysis and design of the protection scheme for a low voltage DC microgrid, in presence of different renewable generators, energy storage systems, loads and front-end converter with the AC grid. The proposed centralized protection scheme overcomes issues of fast fault clearing time, cost effectiveness and selectivity in the case of pole-to-pole fault.
Mass spectrometric imaging of peptide release from neuronal cells within microfluidic devices (2007)

Microfluidic devices are well suited for manipulating and measuring mass limited samples. Here we adapt a microfluidic device containing functionalized surfaces to chemically stimulate a small number of neurons (down to a single neuron), collect the release of neuropeptides, and characterize them using mass spectrometry. As only a small fraction of the peptides present in a neuron are released with physiologically relevant stimulations, the amount of material available for measurement is small, thereby requiring minimal sample loss and high-sensitivity detection. Although a number of detection schemes are used with microfluidic devices, mass spectrometric detection is used here because of its high information content, allowing the characterization of the released peptide complement. Rather than using an on-line approach, off-line analysis is used; after collection of the peptides onto a surface, mass spectrometric imaging interrogates that surface to determine the peptides released from the cell. The overall utility of this scheme is demonstrated using several device formats with measurement of neuropeptides released from Aplysia californica bag cell neurons.
Redox (phospho)lipidomics of signaling in inflammation and programmed cell death (2019)

In addition to the known prominent role of polyunsaturated (phospho)lipids as structural blocks of biomembranes, there is an emerging understanding of another important function of these molecules as a highly diversified signaling language utilized for intra- and extracellular communications. Technological developments in high-resolution mass spectrometry facilitated the development of a new branch of metabolomics, redox lipidomics. Analysis of lipid peroxidation reactions has already identified specific enzymatic mechanisms responsible for the biosynthesis of several unique signals in response to inflammation and regulated cell death programs. Obtaining comprehensive information about millions of signals encoded by oxidized phospholipids, represented by thousands of interactive reactions and pleiotropic (patho)physiological effects, is a daunting task. However, there is still reasonable hope that significant discoveries, of at least some of the important contributors to the overall overwhelmingly complex network of interactions triggered by inflammation, will lead to the discovery of new small molecule regulators and therapeutic modalities. For example, suppression of the production of AA-derived pro-inflammatory mediators, HXA<sub>3</sub> and LTB<sub>4,</sub> by an iPLA<sub>2</sub> γ inhibitor, R-BEL, mitigated injury associated with the activation of pro-inflammatory processes in animals exposed to whole-body irradiation. Further, technological developments promise to make redox lipidomics a powerful approach in the arsenal of diagnostic and therapeutic instruments for personalized medicine of inflammatory diseases and conditions.