Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of Clinical Outcomes among Intensive Care Unit Patients Receiving One or Two Grams of Ceftriaxone Daily

Intensive care unit (ICU) patients may experience ceftriaxone underexposure, but clinical outcomes data are lacking. The objective of this study was to determine the impact of ceftriaxone dosing on clinical outcomes among ICU patients without central nervous system (CNS) infection. A retrospective study of ICU patients receiving intravenous, empirical ceftriaxone for non-CNS infections was conducted. Patients ≥18 years of age who received ≤2 g of ceftriaxone daily for ≥72 h were included and categorized as receiving ceftriaxone 1 g or 2 g daily. ABSTRACT Intensive care unit (ICU) patients may experience ceftriaxone underexposure, but clinical outcomes data are lacking. The objective of this study was to determine the impact of ceftriaxone dosing on clinical outcomes among ICU patients without central nervous system (CNS) infection. A retrospective study of ICU patients receiving intravenous, empirical ceftriaxone for non-CNS infections was conducted. Patients ≥18 years of age who received ≤2 g of ceftriaxone daily for ≥72 h were included and categorized as receiving ceftriaxone 1 g or 2 g daily. The primary, composite outcome was treatment failure, defined as inpatient mortality and/or antibiotic escalation due to clinical worsening. Propensity score matching was performed based on the probability of receiving 2 g of ceftriaxone daily. Multivariable logistic regression determined the association between ceftriaxone dose and treatment failure in a propensity-matched cohort. A total of 212 patients were included in the propensity-matched cohort. The most common diagnoses (83.0%) were pneumonia and urinary tract infection. Treatment failure occurred in 17.0% and 5.7% of patients receiving 1 g and 2 g daily, respectively (P = 0.0156). Overall inpatient mortality was 8.5%. Ceftriaxone 2 g dosing was associated with a reduced likelihood of treatment failure (adjusted odds ratio [aOR] = 0.190; 95% confidence interval [CI] = 0.059 to 0.607). Other independent predictors of treatment failure included sequential organ failure assessment score (aOR = 1.440; 95% CI = 1.254 to 1.653) and creatinine clearance at 72 h from ceftriaxone initiation (aOR = 0.980; 95% CI = 0.971 to 0.999). Therefore, ceftriaxone at 2 g daily, when used as appropriate antimicrobial coverage, may be appropriate for ICU patients with lower mortality risk.
The Role of Torsin AAA+ Proteins in Preserving Nuclear Envelope Integrity and Safeguarding Against Disease

Torsin ATPases are members of the AAA+ (ATPases associated with various cellular activities) superfamily of proteins, which participate in essential cellular processes. While AAA+ proteins are ubiquitously expressed and demonstrate distinct subcellular localizations, Torsins are the only AAA+ to reside within the nuclear envelope (NE) and endoplasmic reticulum (ER) network. Moreover, due to the absence of integral catalytic features, Torsins require the NE- and ER-specific regulatory cofactors, lamina-associated polypeptide 1 (LAP1) and luminal domain like LAP1 (LULL1), to efficiently trigger their atypical mode of ATP hydrolysis. Despite their implication in an ever-growing list of diverse processes, the specific contributions of Torsin/cofactor assemblies in maintaining normal cellular physiology remain largely enigmatic. Resolving gaps in the functional and mechanistic principles of Torsins and their cofactors are of considerable medical importance, as aberrant Torsin behavior is the principal cause of the movement disorder DYT1 early-onset dystonia. In this review, we examine recent findings regarding the phenotypic consequences of compromised Torsin and cofactor activities. In particular, we focus on the molecular features underlying NE defects and the contributions of Torsins to nuclear pore complex biogenesis, as well as the growing implications of Torsins in cellular lipid metabolism. Additionally, we discuss how understanding Torsins may facilitate the study of essential but poorly understood processes at the NE and ER, and aid in the development of therapeutic strategies for dystonia.
5-Ethynyl-2′-deoxycytidine and 5-ethynyl-2′-deoxyuridine are differentially incorporated in cells infected with HSV-1, HCMV, and KSHV viruses

Nucleoside analogues are a valuable experimental tool. Incorporation of these molecules into newly synthesized DNA (i.e. pulse-labeling) is used to monitor cell proliferation or to isolate nascent DNA. Some of the most common nucleoside analogues used for pulse-labeling of DNA in cells are the deoxypyrimidine analogues 5-ethynyl-2′-deoxyuridine (EdU) and 5-ethynyl-2′-deoxycytidine (EdC). Click chemistry enables conjugation of an azide molecule tagged with a fluorescent dye or biotin to the alkyne of the analog, which can then be used to detect incorporation of EdU and EdC into DNA. The use of EdC is often recommended because of the potential cytotoxicity associated with EdU during longer incubations. Here, by comparing the relative incorporation efficiencies of EdU and EdC during short 30-min pulses, we demonstrate significantly lower incorporation of EdC than of EdU in noninfected human fibroblast cells or in cells infected with either human cytomegalovirus or Kaposi's sarcoma-associated herpesvirus. Interestingly, cells infected with herpes simplex virus type-1 (HSV-1) incorporated EdC and EdU at similar levels during short pulses. Of note, exogenous expression of HSV-1 thymidine kinase increased the incorporation efficiency of EdC. These results highlight the limitations when using substituted pyrimidine analogues in pulse-labeling and suggest that EdU is the preferable nucleoside analogue for short pulse-labeling experiments, resulting in increased recovery and sensitivity for downstream applications. This is an important discovery that may help to better characterize the biochemical properties of different nucleoside analogues with a given kinase, ultimately leading to significant differences in labeling efficiency of nascent DNA.
Serological Evaluation of Onchocerciasis and Lymphatic Filariasis Elimination in the Bakoye and Falémé Foci, Mali

Abstract Background Ivermectin-based onchocerciasis elimination, reported in 2009–2012, for Bakoye and Falémé, Mali, supported policy-shifting from morbidity control to elimination of transmission (EOT). These foci are coendemic with lymphatic filariasis (LF). In 2007–2016 mass ivermectin plus albendazole administration was implemented. We report Ov16 (onchocerciasis) and Wb123 (LF) seroprevalence after 24–25 years of treatment to determine if onchocerciasis EOT and LF elimination as a public health problem (EPHP) have been achieved. Methods The SD Bioline Onchocerciasis/LF Ig[immunoglobulin]G4 biplex rapid diagnostic test (RDT) was used in 2186 children aged 3–10 years in 13 villages (plus 2 hamlets) in Bakoye and in 2270 children in 15 villages (plus 1 hamlet) in Falémé. In Bakoye, all-age serosurveys were conducted in 3 historically hyperendemic villages (1867 individuals aged 3 -78 years). Results In Bakoye, IgG4 seropositivity was 0.27% (95% confidence interval [CI] = .13%–.60%) for both Ov16 and Wb123 antigens. In Falémé, Ov16 and Wb123 seroprevalence was 0.04% (95% CI = .01%–.25%) and 0.09% (95% CI = .02%–.32%), respectively. Ov16-seropositive children were from historically meso/hyperendemic villages. Ov16 positivity was <2% in ≤14 year-olds, and 16% in ≥40 year-olds. Wb123 seropositivity was <2% in ≤39 year-olds, reaching 3% in ≥40 year-olds. Conclusions Notwithstanding uncertainty in the biplex RDT sensitivity, Ov16 and Wb123 seroprevalence among children in Bakoye and Falémé is consistent with EOT (onchocerciasis) and EPHP (LF) since stopping treatment in 2016. The few Ov16-seropositive children should be skin-snip polymerase chain reaction tested and followed up.
Examining the relationship between rheumatoid arthritis, multimorbidity and adverse health-related outcomes: A systematic review protocol

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterised by articular inflammation and systemic complications. Multimorbidity (the presence of two or more long-term health conditions) is highly prevalent in people with RA but the effect of multimorbidity on mortality and other health-related outcomes is poorly understood. Objective: To determine what is known about the effect, if any, of multimorbidity on mortality and health-related outcomes in individuals with RA. Design: Systematic review of the literature. The following electronic medical databases will be searched: MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, The Cochrane Library and Scopus. Included studies will be quality appraised using the Quality in Prognostic Studies tool developed by the Cochrane Prognosis Methods Group. A narrative synthesis of findings will be undertaken and meta-analyses considered, if appropriate. This protocol adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols 2015 guidelines, ensuring the quality of the review. Conclusions: Understanding the influence of multimorbidity on mortality and other health-related outcomes in RA will provide an important basis of knowledge with the potential to improve future clinical management of RA. PROSPERO registration number: CRD42019137756.
Death in low-risk cardiac surgery revisited

Background A systematic review of low-risk death has been shown successful in identifying system weaknesses. The aim was to analyse early mortality in low-risk patients undergoing cardiac surgery and to determine the cause of death, classify if they were unavoidable or potentially preventable as a result of technical or system errors. Methods We included all low-risk patients who underwent cardiac surgery at our institution from 1 September 2009 to 31 August 2019. In patients operated between 2009 and 2011, we defined low risk as an additive European System for Cardiac Operative Risk Evaluation (EuroSCORE) I less than or equal to 3, and from 2012 and onwards as a EuroSCORE II less than or equal to 1.5. The medical records for the patients who died within 30 days of surgery were thoroughly examined and the cause of death was classified as cardiac or non-cardiac. Furthermore, deaths were categorised as not preventable, preventable (technical error) or preventable (system error). Results During the study period 3103 low-risk patients underwent surgery, and 11 patients died within 30 days of the operation (0.35%). Six of these (55%) were classified as preventable and five non-preventable. Four of the preventable deaths were classified as technical errors and two were due to system errors. Conclusions A repeated systematic review of deaths in patients with a low preoperative risk showed that a majority of deaths were preventable, and therefore potentially avoidable. Similar to the previous assessment at our unit, mortality was very low and failure to communicate remains a modifiable factor that should be addressed.
Uncovering the moral heuristics of altruism: A philosophical scale

Extant research suggests that individuals employ traditional moral heuristics to support their observed altruistic behavior; yet findings have largely been limited to inductive extrapolation and rely on relatively few traditional frames in so doing, namely, deontology in organizational behavior and virtue theory in law and economics. Given that these and competing moral frames such as utilitarianism can manifest as identical behavior, we develop a moral framing instrument—the Philosophical Moral-Framing Measure (PMFM)—to expand and distinguish traditional frames associated and disassociated with observed altruistic behavior. The validation of our instrument based on 1015 subjects in 3 separate real stakes scenarios indicates that heuristic forms of deontology, virtue-theory, and utilitarianism are strongly related to such behavior, and that egoism is an inhibitor. It also suggests that deontic and virtue-theoretical frames may be commonly perceived as intertwined and opens the door for new research on self-abnegation, namely, a perceived moral obligation toward suffering and self-denial. These findings hold the potential to inform ongoing conversations regarding organizational citizenship and moral crowding out, namely, how financial incentives can undermine altruistic behavior.
Model Predictive Controller Based on Online Obtaining of Softness Factor and Fusion Velocity for Automatic Train Operation

This paper develops an improved model predictive controller based on the online obtaining of softness factor and fusion velocity for automatic train operation to enhance the tracking control performance. Specifically, the softness factor of the improved model predictive control algorithm is not a constant, conversely, an improved online adaptive adjusting method for softness factor based on fuzzy satisfaction of system output value and velocity distance trajectory characteristic is adopted, and an improved whale optimization algorithm has been proposed to solve the adjustable parameters; meanwhile, the system output value for automatic train operation is not sampled by a normal speed sensor, on the contrary, an improved online velocity sampled method for the system output value based on a fusion velocity model and an intelligent digital torque sensor is applied. In addition, the two improved strategies proposed take the real-time storage and calculation capacities of the core chip of the controller into account. Therefore, the proposed improved strategies (I) have good performance in tracking precision, (II) are simple and easily conducted, and (III) can ensure the accomplishing of computational tasks in real-time. Finally, to verify the effectiveness of the improved model predictive controller, the Matlab/simulink simulation and hardware-in-the-loop simulation (HILS) are adopted for automatic train operation tracking control, and the tracking control simulation results indicate that the improved model predictive controller has better tracking control effectiveness compared with the existing traditional improved model predictive controller.
Thoracic gas compression during forced expiration is greater in men than women

Intrapleural pressure during a forced vital capacity (VC) maneuver is often in excess of that required to generate maximal expiratory airflow. This excess pressure compresses alveolar gas (i.e., thoracic gas compression [TGC]), resulting in underestimated forced expiratory flows (FEFs) at a given lung volume. It is unknown if TGC is influenced by sex; however, because men have larger lungs and stronger respiratory muscles, we hypothesized that men would have greater TGC. We examined TGC across the “effort‐dependent” region of VC in healthy young men (n = 11) and women (n = 12). Subjects performed VC maneuvers at varying efforts while airflow, volume, and esophageal pressure (POES) were measured. Quasistatic expiratory deflation curves were used to obtain lung recoil (PLUNG) and alveolar pressures (i.e., PALV = POES–PLUNG). The raw maximal expiratory flow–volume (MEFVraw) curve was obtained from the “maximum effort” VC maneuver. The TGC‐corrected curve was obtained by constructing a “maximal perimeter” curve from all VC efforts (MEFVcorr). TGC was examined via differences between curves in FEFs (∆FEF), area under the expiratory curves (∆AEX), and estimated compressed gas volume (∆VGC) across the VC range. Men displayed greater total ∆AEX (5.4 ± 2.0 vs. 2.0 ± 1.5 L2·s−1; p < .001). ∆FEF was greater in men at 25% of exhaled volume only (p < .05), whereas ∆VGC was systematically greater in men across the entire VC (main effect; p < .05). PALV was also greater in men throughout forced expiration (p < .01). Taken together, these findings demonstrate that men display more TGC, occurring early in forced expiration, likely due to greater expiratory pressures throughout the forced VC maneuver.
Different Types of Gel Carriers as Metronidazole Delivery Systems to the Oral Mucosa

Periodontal diseases are some of the most widespread oral afflictions, and they are labeled as chronic infections caused by the accumulation of bacteria in dental plaque that produces localized inflammation of the periodontium. The use of local drug delivery systems to treat periodontal diseases has received greater attention, because the active substance is targeted directly to the affected area, which minimizes its systemic side effects. Therefore, the purpose of the investigation was to develop and characterize different types of gel formulations—bigel, hydrogel and oleogel—as local delivery systems containing metronidazole (MET), which can be applied to the oral mucosa. The influence of the formulation type on the mechanical, rheological and mucoadhesive properties were examined. Moreover, in vitro release of metronidazole, its ex vivo permeation through buccal porcine mucosa and antimicrobial activity measured by the plate diffusion method were estimated. It was found that the gel formulations obtained were non-Newtonian systems, showing a shear-thinning behavior and thixotropic properties with good textural features such as firmness, compressibility and adhesiveness. Moreover, the preparations designed possessed beneficial mucoadhesive properties. The formulated hydrogels and bigels containing micronized MET were considered as better formulations in terms of drug release and antimicrobial activity compared to commercially available metronidazole ointment. An ex vivo permeation study with the use of porcine buccal mucosa demonstrated that the bigel formulation was characterized by higher initial permeability rate providing a fast therapeutic effect with simultaneous moderate retention in mucosal tissue to decrease the risk of local cytotoxicity.
Longitudinal assessment of tissue properties and cardiac diffusion metrics of the ex vivo porcine heart at 7 T: Impact of continuous tissue fixation using formalin

In this study we aimed to assess the effects of continuous formalin fixation on diffusion and relaxation metrics of the ex vivo porcine heart at 7 T. Magnetic resonance imaging was performed on eight piglet hearts using a 7 T whole body system. Hearts were measured fresh within 3 hours of cardiac arrest followed by immersion in 10% neutral buffered formalin. T2* and T2 were assessed using a gradient multi‐echo and multi‐echo spin echo sequence, respectively. A spin echo and a custom stimulated echo sequence were employed to assess diffusion time‐dependent changes in metrics of cardiac diffusion tensor imaging. SNR was determined for b = 0 images. Scans were performed for 5 mm thick apical, midcavity and basal slices (in‐plane resolution: 1 mm) and repeated 7, 15, 50, 100 and 200 days postfixation. Eigenvalues of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) decreased significantly (P < 0.05) following fixation. Relative to fresh hearts, FA values 7 and 200 days postfixation were 90% and 80%, while respective relative ADC values at those fixation stages were 78% and 92%. Statistical helix and sheetlet angle distributions as well as respective mean and median values showed no systematic influence of continuous formalin fixation. Similar to changes in the ADC, values for T2, T2* and SNR dropped initially postfixation. Respective relative values compared with fresh hearts at day 7 were 64%, 79% and 68%, whereas continuous fixation restored T2, T2* and SNR leading to relative values of 74%, 100%, and 81% at day 200, respectively. Relaxation parameters and diffusion metrics are significantly altered by continuous formalin fixation. The preservation of microstructure metrics following prolonged fixation is a key finding that may enable future studies of ventricular remodeling in cardiac pathologies.
Mediterranean radiocarbon offsets and calendar dates for prehistory

Intra-annual offsets in Northern Hemisphere atmospheric radiocarbon levels challenge and complicate Old World radiocarbon dating. A single Northern Hemisphere calibration curve has formed the basis of radiocarbon dating in Europe and the Mediterranean for five decades, setting the time frame for prehistory. However, as measurement precision increases, there is mounting evidence for some small but substantive regional (partly growing season) offsets in same-year radiocarbon levels. Controlling for interlaboratory variation, we compare radiocarbon data from Europe and the Mediterranean in the second to earlier first millennia BCE. Consistent with recent findings in the second millennium CE, these data suggest that some small, but critical, periods of variation for Mediterranean radiocarbon levels exist, especially associated with major reversals or plateaus in the atmospheric radiocarbon record. At high precision, these variations potentially affect calendar dates for prehistory by up to a few decades, including, for example, Egyptian history and the much-debated Thera/Santorini volcanic eruption.
Nanobiohybrids: Materials approaches for bioaugmentation

We review recent advances and prospects of interfacing functional nanomaterials with biological systems for nanobiohybrids. Nanobiohybrids, synthesized by integrating functional nanomaterials with living systems, have emerged as an exciting branch of research at the interface of materials engineering and biological science. Nanobiohybrids use synthetic nanomaterials to impart organisms with emergent properties outside their scope of evolution. Consequently, they endow new or augmented properties that are either innate or exogenous, such as enhanced tolerance against stress, programmed metabolism and proliferation, artificial photosynthesis, or conductivity. Advances in new materials design and processing technologies made it possible to tailor the physicochemical properties of the nanomaterials coupled with the biological systems. To date, many different types of nanomaterials have been integrated with various biological systems from simple biomolecules to complex multicellular organisms. Here, we provide a critical overview of recent developments of nanobiohybrids that enable new or augmented biological functions that show promise in high-tech applications across many disciplines, including energy harvesting, biocatalysis, biosensing, medicine, and robotics.
Sparse Graph Regularized Mesh Color Edit Propagation

Mesh color edit propagation aims to propagate the color from a few color strokes to the whole mesh, which is useful for mesh colorization, color enhancement and color editing, etc. Compared with image edit propagation, luminance information is not available for 3D mesh data, so the color edit propagation is more difficult on 3D meshes than images, with far less research carried out. This paper proposes a novel solution based on sparse graph regularization. Firstly, a few color strokes are interactively drawn by the user, and then the color will be propagated to the whole mesh by minimizing a sparse graph regularized nonlinear energy function. The proposed method effectively measures geometric similarity over shapes by using a set of complementary multiscale feature descriptors, and effectively controls color bleeding via a sparse $\ell _{1}$ optimization rather than quadratic minimization used in existing work. The proposed framework can be applied for the task of interactive mesh colorization, mesh color enhancement and mesh color editing. Extensive qualitative and quantitative experiments show that the proposed method outperforms the state-of-the-art methods.