Miracle-dz/UniFAR-FTUs huggingface dataset:
Non-alcoholic fatty liver disease – a procoagulant condition?

Non-alcoholic fatty liver disease (NAFLD) is associated with a number of extrahepatic comorbidities and considerable cardiovascular morbidity and mortality, which is possibly related to coagulation changes associated with metabolic syndrome. Coagulation disorders are common in patients with liver disease of any etiology, and here we review possible alterations in coagulation cascade specific to NAFLD. We discuss derangements in the coagulation cascade and fibrinolysis, endothelial dysfunction, and platelet abnormalities as possible culprits for altered coagulation and explore the significance of these changes for potential treatment targets.
Influence of Lipid Excipients on Platelet Function and the Pharmacodynamic Effects of Aspirin

Abstract: The combination of pharmaceutical lipid excipients with aspirin in a novel liquid oral formulation (Vazalore) limits gastrointestinal toxicity of aspirin. This study was performed to determine whether the lipid excipients influence the pharmacodynamic effects of aspirin and whether the excipients directly affect platelet function. The pharmacodynamic effects of aspirin were assessed over a range of concentrations designed to exert limited to maximal inhibition of cyclooxygenase-1 (COX1) necessary for thromboxane A2 production. Platelet aggregation induced by arachidonic acid and assessed with the use of light transmission aggregometry was used as a direct measure of the inhibition of COX1 by aspirin. Flow cytometry was used to assess the direct effect of excipients on platelet function. Twice the ratio of lipid excipient to aspirin used in the formulation of the novel oral agent was used. Blood was taken from 20 healthy subjects and anticoagulated with trisodium citrate (3.2%, 1:10 vol/vol). Aspirin and excipients were added in vitro and incubated for 10 minutes before performance of light transmission aggregometry and flow cytometry. The excipients did not limit the pharmacodynamic effects of aspirin. When the extent of inhibition of platelet aggregation was limited, the excipients tended to enhance pharmacodynamic effects. The excipients did not activate platelets in the absence of agonist and did not alter activation of platelets in response to adenosine diphosphate, arachidonic acid, thrombin, or convulxin (a collagen mimetic). Lipid excipients used in an oral formulation of aspirin do not impair the pharmacodynamic effects of aspirin and do not alter platelet function.
Evaluation of a Denuder-MOUDI-PUF Sampling System to Measure the Size Distribution of Semi-Volatile Polycyclic Aromatic Hydrocarbons in the Atmosphere

This study describes a field comparison conducted between 2 methods employing different MOUDI impactor configurations to evaluate their performance in sampling and measurement of the size distribution of 15 priority pollutant polycyclic aromatic hydrocarbons (PAHs). Samples were collected during 24 h periods approximately every 7th day, beginning at 8:00 AM, in 2 different sites of the Los Angeles Basin. One site was near Central Los Angeles in an area impacted by high vehicular traffic, whereas the other site was located about 60 km downwind of central Los Angeles (receptor site). Particle samples from about 43 m 3 of air were collected using collocated MOUDI impactors and classified in 3 aerodynamic diameter size intervals: 0-0.18 w m (ultrafine mode I), 0.18-2.5 w m (accumulation mode II), and 2.5-10 w m (coarse mode III). One MOUDI operated in the conventional mode, the other with a vapor trapping system that included an XAD-4 coated annular denuder placed upstream of the impactor and a polyurethane foam plug (PUF) placed in series behind the impactor. PAHs were separated and quantified by HPLC with fluorescence detection optimized for the highest sensitivity. The results showed that for both sites, using either sampling system, the size distributions obtained are similar for the less volatile PAHs (log [ p ° L ] h m 3.2), but different for the more volatile PAHs (log [ p ° L ] S m 2.06). In the central Los Angeles site, the largest PAH fraction was found in the 0-0.18 w m (mode I) size range, typical of primary emissions. At the downwind location, the largest fraction was in the 0.18-2.5 w m (mode II) size range, consistent with an "aged" aerosol. At both sites, albeit not statistically significant, the mean regular to denuded MOUDI mass ratios were 33-36% and 11-19% higher, respectively, for the more volatile and the less volatile PAH groups. Sampling with the regular MOUDI configuration is simpler and thus recommended for measurement of the size distribution of PAHs in either group.
HP1β carries an acidic linker domain and requires H3K9me3 for phase separation

ABSTRACT Liquid-liquid phase separation (LLPS) mediated formation of membraneless organelles has been proposed to coordinate biological processes in space and time. Previously, the formation of phase-separated droplets was described as a unique property of HP1α. Here, we demonstrate that the positive net charge of the intrinsically disordered hinge region (IDR-H) of HP1 proteins is critical for phase separation and that the exchange of four acidic amino acids is sufficient to confer LLPS properties to HP1β. Surprisingly, the addition of mono-nucleosomes promoted H3K9me3-dependent LLPS of HP1β which could be specifically disrupted with methylated but not acetylated H3K9 peptides. HP1β mutants defective in H3K9me3 binding were less efficient in phase separationin vitro and failed to accumulate at heterochromatin in vivo. We propose that multivalent interactions of HP1β with H3K9me3-modified nucleosomes via its chromodomain and dimerization via its chromoshadow domain enable phase separation and contribute to the formation of heterochromatin compartments in vivo.
A Two-Stream Continual Learning System With Variational Domain-Agnostic Feature Replay

Learning in nonstationary environments is one of the biggest challenges in machine learning. Nonstationarity can be caused by either task drift, i.e., the drift in the conditional distribution of labels given the input data, or the domain drift, i.e., the drift in the marginal distribution of the input data. This article aims to tackle this challenge with a modularized two-stream continual learning (CL) system, where the model is required to learn new tasks from a support stream and adapted to new domains in the query stream while maintaining previously learned knowledge. To deal with both drifts within and across the two streams, we propose a variational domain-agnostic feature replay-based approach that decouples the system into three modules: an inference module that filters the input data from the two streams into domain-agnostic representations, a generative module that facilitates the high-level knowledge transfer, and a solver module that applies the filtered and transferable knowledge to solve the queries. We demonstrate the effectiveness of our proposed approach in addressing the two fundamental scenarios and complex scenarios in two-stream CL.
Hunting bats adjust their echolocation to receive weak prey echoes for clutter reduction

Bat-borne tags reveal faint echoes and fast sensorimotor responses that reduce acoustic clutter in complex foraging habitats. How animals extract information from their surroundings to guide motor patterns is central to their survival. Here, we use echo-recording tags to show how wild hunting bats adjust their sensory strategies to their prey and natural environment. When searching, bats maximize the chances of detecting small prey by using large sensory volumes. During prey pursuit, they trade spatial for temporal information by reducing sensory volumes while increasing update rate and redundancy of their sensory scenes. These adjustments lead to very weak prey echoes that bats protect from interference by segregating prey sensory streams from the background using a combination of fast-acting sensory and motor strategies. Counterintuitively, these weak sensory scenes allow bats to be efficient hunters close to background clutter broadening the niches available to hunt for insects.
Transformation of Borrelia burgdorferi

Transformation techniques used to genetically manipulate Borrelia burgdorferi, the agent of Lyme disease, play a critical role in generating mutants that facilitate analyses of the role of genes in the pathophysiology of this bacterium. A number of borrelial mutants have been successfully isolated and characterized since the first electrotransformation procedure was established 25 years ago (Samuels, 1995). This article is directed at additional considerations for transforming infectious B. burgdorferi to generate strains retaining the plasmid profile of the parental strain, enabling analysis of transformants for in vitro and in vivo phenotypes. These methods are built on previously published protocols and are intended to add steps and tips to enhance transformation efficiency and recovery of strains amenable for studies involving colonization, survival, and transmission of B. burgdorferi during the vector and vertebrate phases of infection. © 2021 Wiley Periodicals LLC.
Physicians’ Use of the Computerized Physician Order Entry System for Medication Prescribing: Systematic Review

Background Computerized physician order entry (CPOE) systems in health care settings have many benefits for prescribing medication, such as improved quality of patient care and patient safety. However, to achieve their full potential, the factors influencing the usage of CPOE systems by physicians must be identified and understood. Objective The aim of this study is to identify the factors influencing the usage of CPOE systems by physicians for medication prescribing in their clinical practice. Methods We conducted a systematic search of the literature on this topic using four databases: PubMed, CINAHL, Ovid MEDLINE, and Embase. Searches were performed from September 2019 to December 2019. The retrieved papers were screened by examining the titles and abstracts of relevant studies; two reviewers screened the full text of potentially relevant papers for inclusion in the review. Qualitative, quantitative, and mixed methods studies with the aim of conducting assessments or investigations of factors influencing the use of CPOE for medication prescribing among physicians were included. The identified factors were grouped based on constructs from two models: the unified theory of acceptance and use of technology model and the Delone and McLean Information System Success Model. We used the Mixed Method Appraisal Tool to assess the quality of the included studies and narrative synthesis to report the results. Results A total of 11 articles were included in the review, and 37 factors related to the usage of CPOE systems were identified as the factors influencing how physicians used CPOE for medication prescribing. These factors represented three main themes: individual, technological, and organizational. Conclusions This study identified the common factors that influenced the usage of CPOE systems by physicians for medication prescribing regardless of the type of setting or the duration of the use of a system by participants. Our findings can be used to inform implementation and support the usage of the CPOE system by physicians.
Oligometastatic Bone Disease in Castration-Sensitive Prostate Cancer Patients Treated With Stereotactic Body Radiotherapy Using 68Ga-PSMA PET/CT

Purpose To evaluate the outcomes of metastasis-directed treatment (MDT) using stereotactic body radiotherapy (SBRT) for bone-only oligometastasis (OM) detected with gallium prostate-specific membrane antigen (68Ga-PSMA) PET/CT in castration-sensitive prostate cancer (PC) patients. Methods In this multi-institutional study, clinical data of 74 PC patients with 153 bone lesions who were undergoing MDT were retrospectively evaluated. Twenty-seven patients (36.5%) had synchronous, and 47 (63.5%) had metachronous OM. All patients had PC with 5 metastases or fewer detected by 68Ga-PSMA PET/CT and treated using SBRT with a median dose of 20 Gy. The prognostic factors for PC-specific survival (PCSS) and progression-free survival (PFS) were analyzed. Results The median follow-up was 27.3 months. Patients with synchronous OM were older and received higher rates of androgen deprivation therapy after SBRT compared with patients with metachronous OM. The 2-year PCSS and PFS rates were 92.0% and 72.0%, respectively. A prostate-specific antigen (PSA) decline was observed in 56 patients (75.7%), and 48 (64.9%) had a PSA response defined as at least 25% decrease of PSA after MDT. The 2-year local control rate per lesion was 95.4%. In multivariate analysis, single OM and PSA response after MDT were significant predictors for better PCSS and PFS. In-field recurrence was observed in 4 patients (6.5%) with 10 lesions at a median of 13.1 months after MDT completion. No serious late toxicity was observed. Conclusions We demonstrated that SBRT is an efficient and well-tolerated treatment option for PC patients with 5 bone-only oligometastases or fewer detected with 68Ga-PSMA PET/CT.
The Kainic Acid Models of Temporal Lobe Epilepsy

Abstract Experimental models of epilepsy are useful to identify potential mechanisms of epileptogenesis, seizure genesis, comorbidities, and treatment efficacy. The kainic acid (KA) model is one of the most commonly used. Several modes of administration of KA exist, each producing different effects in a strain-, species-, gender-, and age-dependent manner. In this review, we discuss the advantages and limitations of the various forms of KA administration (systemic, intrahippocampal, and intranasal), as well as the histologic, electrophysiological, and behavioral outcomes in different strains and species. We attempt a personal perspective and discuss areas where work is needed. The diversity of KA models and their outcomes offers researchers a rich palette of phenotypes, which may be relevant to specific traits found in patients with temporal lobe epilepsy.
Fitness and fur colouration - testing the camouflage and thermoregulation hypotheses in an Arctic mammal.

1. Selection for crypsis has been recognised as an important ecological driver of animal coloration, whereas the relative importance of thermoregulation is more contentious with mixed empirical support. A potential thermal advantage of darker individuals has been observed in a wide range of animal species. Arctic animals that exhibit colour polymorphisms and undergo seasonal colour moults are interesting study subjects for testing the two alternative hypotheses: demographic performance of different colour morphs might be differentially affected by snow cover with a cryptic advantage for lighter morphs, or conversely by winter temperature with a thermal advantage for darker morphs. 2. In this study, we explored whether camouflage and thermoregulation might explain differences in reproduction and survival between the white and blue colour morphs of the Arctic fox (Vulpes lagopus) under natural conditions. 3. Juvenile and adult survival, breeding propensity, and litter size were measured for 798 captive-bred and released or wild-born Arctic foxes monitored during an 11-year period (2007-2017) in two subpopulations in south-central Norway. We investigated the proportion of the two colour morphs and compared their demographic performance in relation to spatial variation in duration of snow cover, onset of snow season, and winter temperatures. 4. After population re-establishment, a higher proportion of blue individuals was observed among wild-born Arctic foxes compared to the proportion of blue foxes released from the captive population. Our field study provides the first evidence for an effect of colour morph on the reproductive performance of Arctic foxes under natural conditions, with a higher breeding propensity of the blue morph compared to the white one. Performance of the two colour morphs was not differentially affected by the climatic variables, except for juvenile survival. Blue morph juveniles showed a tendency for higher survival under colder winter temperatures but lower survival under warmer temperatures compared to white morph juveniles. 5. Overall, our findings do not consistently support predictions of the camouflage or the thermoregulation hypotheses. The higher success of blue foxes suggests an advantage of the dark morph not directly related to disruptive selection by crypsis or thermoregulation. Our results rather point to physiological adaptations and behavioural traits not necessarily connected to thermoregulation, such as stress response, immune function, sexual behaviour, and aggressiveness. Our findings highlight the need to explore the potential role of genetic linkage or pleiotropy in influencing the fitness of white and blue Arctic foxes as well as other species with colour polymorphisms.
A retrospective review of the use of a nanocrystalline silver dressing in the management of open chronic wounds in the community

As part of an infection management protocol, antimicrobial dressings offer an appropriate, cost‐effective choice for the management of localised bioburden in chronic wounds. The choice of antimicrobial can impact significantly not only on the treatment outcomes and cost but also on the safety and well‐being of the patient. This retrospective study investigates these outcomes comparing health care records of 2572 patients with open chronic wounds, who were treated either with an Integrated Care Wound Bundle (ICB) including nanocrystalline silver (NCS) dressings (n = 330) or without NCS dressings and not on a ICB (n = 2242) in the community from March 2016 to March 2018. Wounds treated in the NCS dressing treatment bundle had a mean healing time of 10.46 weeks, vs 25.49 weeks for the non‐ICB treated wounds. In addition, the average interval time between dressing changes was in favour of the NCS dressing treatment bundle (3.98 vs 1.87 days), contributing to a substantial reduction in mean treatment labour costs ($1251 vs $6488). The use of a NCS dressing demonstrated improved efficacy and cost effectiveness of labour required for chronic wound management; highlighting the importance of choosing an effective antimicrobial dressing as part of an infection management protocol.
Contribution of Free-Text Comments to the Burden of Documentation: Assessment and Analysis of Vital Sign Comments in Flowsheets

Background Documentation burden is a common problem with modern electronic health record (EHR) systems. To reduce this burden, various recording methods (eg, voice recorders or motion sensors) have been proposed. However, these solutions are in an early prototype phase and are unlikely to transition into practice in the near future. A more pragmatic alternative is to directly modify the implementation of the existing functionalities of an EHR system. Objective This study aims to assess the nature of free-text comments entered into EHR flowsheets that supplement quantitative vital sign values and examine opportunities to simplify functionality and reduce documentation burden. Methods We evaluated 209,055 vital sign comments in flowsheets that were generated in the Epic EHR system at the Vanderbilt University Medical Center in 2018. We applied topic modeling, as well as the natural language processing Clinical Language Annotation, Modeling, and Processing software system, to extract generally discussed topics and detailed medical terms (expressed as probability distribution) to investigate the stories communicated in these comments. Results Our analysis showed that 63.33% (6053/9557) of the users who entered vital signs made at least one free-text comment in vital sign flowsheet entries. The user roles that were most likely to compose comments were registered nurse, technician, and licensed nurse. The most frequently identified topics were the notification of a result to health care providers (0.347), the context of a measurement (0.307), and an inability to obtain a vital sign (0.224). There were 4187 unique medical terms that were extracted from 46,029 (0.220) comments, including many symptom-related terms such as “pain,” “upset,” “dizziness,” “coughing,” “anxiety,” “distress,” and “fever” and drug-related terms such as “tylenol,” “anesthesia,” “cannula,” “oxygen,” “motrin,” “rituxan,” and “labetalol. ” Conclusions Considering that flowsheet comments are generally not displayed or automatically pulled into any clinical notes, our findings suggest that the flowsheet comment functionality can be simplified (eg, via structured response fields instead of a text input dialog) to reduce health care provider effort. Moreover, rich and clinically important medical terms such as medications and symptoms should be explicitly recorded in clinical notes for better visibility.
The potential for histone deacetylase (HDAC) inhibitors as cestocidal drugs

Background Echinococcosis and cysticercosis are neglected tropical diseases caused by cestode parasites (family Taeniidae). Not only there is a small number of approved anthelmintics for the treatment of these cestodiases, but also some of them are not highly effective against larval stages, such that identifying novel drug targets and their associated compounds is critical. Histone deacetylase (HDAC) enzymes are validated drug targets in cancers and other diseases, and have been gaining relevance for developing new potential anti-parasitic treatments in the last years. Here, we present the anthelmintic profile for a panel of recently developed HDAC inhibitors against the model cestode Mesocestoides vogae (syn. M. corti). Methodology/Principal findings Phenotypic screening was performed on M. vogae by motility measurements and optical microscopic observations. Some HDAC inhibitors showed potent anthelmintic activities; three of them -entinostat, TH65, and TH92- had pronounced anthelmintic effects, reducing parasite viability by ~100% at concentrations of ≤ 20 μM. These compounds were selected for further characterization and showed anthelmintic effects in the micromolar range and in a time- and dose-dependent manner. Moreover, these compounds induced major alterations on the morphology and ultrastructural features of M. vogae. The potencies of these compounds were higher than albendazole and the anthelmintic effects were irreversible. Additionally, we evaluated pairwise drug combinations of these HDAC inhibitors and albendazole. The results suggested a positive interaction in the anthelmintic effect for individual pairs of compounds. Due to the maximum dose approved for entinostat, adjustments in the dose regime and/or combinations with currently-used anthelmintic drugs are needed, and the selectivity of TH65 and TH92 towards parasite targets should be assessed. Conclusion, significance The results presented here suggest that HDAC inhibitors represent novel and potent drug candidates against cestodes and pave the way to understanding the roles of HDACs in these parasites.
Enhancement of Interconnectivity in the Channels of Pentacene Thin‐Film Transistors and Its Effect on Field‐Effect Mobility

With the aim of improving the field‐effect mobility of transistors by promoting the interconnectivity of the grains in pentacene thin films, deposition conditions of the pentacene molecules using one‐step (total thickness of layer 50 nm: 0.1 Å s–1) and two‐step (first layer 10 nm: 0.1 Å s–1, second layer 40 nm: 4.0 Å s–1) depositions are controlled. Significantly, it is found that the continuities of the pentacene thin films vary with the deposition conditions of the pentacene molecules. Specifically, a smaller number of voids is observed at the interface for the two‐step deposition, which results in field‐effect mobilities as high as 1.2 cm2 V–1 s–1; these are higher by more than a factor of two than those of the pentacene films deposited in one step. This remarkable increase in field‐effect mobility is due in particular to the interconnectivity of the pentacene grains near the insulator substrate.