Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of Hospital Readmission After Total Hip and Total Knee Arthroplasty vs Spinal Surgery After Implementation of the Hospital Readmissions Reduction Program

Key Points Question Is the US Hospital Readmissions Reduction Program associated with a greater decrease in unplanned readmissions after targeted surgical procedures when compared with similar nontargeted procedures? Findings In this nationwide, all-payer cohort study of 6 687 007 weighted index surgical admissions, implementation of the Hospital Readmissions Reduction Program was associated with a decrease of 0.018% per month in the risk-adjusted readmission rate after targeted procedures, while the readmission rate after nontargeted procedures remained constant, a difference that was statistically significant. Meaning Readmission trends appear to be consistent with hospitals’ response to the possibility of Hospital Readmissions Reduction Program penalties after total hip arthroplasty and total knee arthroplasty.
Photoreactivity of the Nonsteroidal Anti‐inflammatory 2‐Arylpropionic Acids with Photosensitizing Side Effects ¶

The photoreactivity of the nonsteroidal anti‐inflammatory 2‐arylpropionic acids benoxaprofen, carprofen, naproxen, ketoprofen, tiaprofenic acid, and suprofen is reviewed with special emphasis on fundamental photophysical and photochemical properties. The absorption and emission properties of the excited states of these drugs as well as their main photodegradation routes are summarized. The photochemical mechanisms are discussed on the basis of product studies and detection of short‐lived intermediates by means of laser flash photolysis. After dealing with the unimolecular processes, attention is focused on the photosensitized reactions of key biomolecules, such as lipids, proteins or nucleic acids. Finally, a short section on the photobiological effects on simple biological models is also included. Although some earlier citations are included, the literature coverage is in general limited to the last decade.
Strong photosynthetic acclimation and enhanced water‐use efficiency in grassland functional groups persist over 21 years of CO2 enrichment, independent of nitrogen supply

Uncertainty about long‐term leaf‐level responses to atmospheric CO2 rise is a major knowledge gap that exists because of limited empirical data. Thus, it remains unclear how responses of leaf gas exchange to elevated CO2 (eCO2) vary among plant species and functional groups, or across different levels of nutrient supply, and whether they persist over time for long‐lived perennials. Here, we report the effects of eCO2 on rates of net photosynthesis and stomatal conductance in 14 perennial grassland species from four functional groups over two decades in a Minnesota Free‐Air CO2 Enrichment experiment, BioCON. Monocultures of species belonging to C3 grasses, C4 grasses, forbs, and legumes were exposed to two levels of CO2 and nitrogen supply in factorial combinations over 21 years. eCO2 increased photosynthesis by 12.9% on average in C3 species, substantially less than model predictions of instantaneous responses based on physiological theory and results of other studies, even those spanning multiple years. Acclimation of photosynthesis to eCO2 was observed beginning in the first year and did not strengthen through time. Yet, contrary to expectations, the response of photosynthesis to eCO2 was not enhanced by increased nitrogen supply. Differences in responses among herbaceous plant functional groups were modest, with legumes responding the most and C4 grasses the least as expected, but did not further diverge over time. Leaf‐level water‐use efficiency increased by 50% under eCO2 primarily because of reduced stomatal conductance. Our results imply that enhanced nitrogen supply will not necessarily diminish photosynthetic acclimation to eCO2 in nitrogen‐limited systems, and that significant and consistent declines in stomatal conductance and increases in water‐use efficiency under eCO2 may allow plants to better withstand drought.
Modelling of Coupled Shrinkage and Creep in Multiphase Formulations for Hardening Concrete

The durability and serviceability of concrete structures is influenced by both the early-age behavior of concrete as well as its long-term response in terms of shrinkage and creep. Hygro-thermo-chemo-mechanical models, as they are used in the present publication, offer the possibility to consistently model the behavior of concrete from the first hours to several years. However, shortcomings of the formulation based on effective stress, which is usually employed in such multiphase models, were identified. As a remedy, two alternative formulations with a different coupling of shrinkage and creep are proposed in the present publication. Both assume viscous flow creep to be driven by total stress instead of effective stress, while viscoelastic creep is driven either by total or effective stress. Therefore, in contrast to the formulation based on effective stress, they predict a limit value for shrinkage as observed in long-term drying shrinkage tests. Shrinkage parameters for the new formulations are calibrated based on drying shrinkage data obtained from thin slices. The calibration process is straightforward for the new formulations since they decouple shrinkage and viscous flow creep. The different formulations are compared using results from shrinkage tests on sealed and unsealed cylindrical specimens. Shrinkage strain predictions are significantly improved by the new formulations.
Transcriptome Analysis of Clinopodium chinense (Benth.) O. Kuntze and Identification of Genes Involved in Triterpenoid Saponin Biosynthesis

Clinopodium chinense (Benth.) O. Kuntze (C. chinense) is an important herb in traditional Chinese medicine. Triterpenoid saponins are a major class of active compounds in C. chinense with broad pharmacological activities and hemostatic, antitumor, and anti-hyperglycemic effects. To identify genes involved in triterpenoid saponin biosynthesis, transcriptomic analyses of leaves, stems, and roots from C. chinense were performed. A total of 135,968 unigenes were obtained by assembling the leaf, stem, and root transcripts, of which 102,154 were annotated in public databases. Differentially expressed genes were determined based on expression profile analysis and analyzed for differential expression of unique genes related to triterpenoid saponin biosynthesis. Multiple unigenes encoding crucial enzymes or transcription factors involved in triterpenoid saponin synthesis were identified and analyzed. The expression levels of unigenes encoding enzymes were experimentally validated using quantitative real-time PCR. This study greatly broadens the public transcriptome database for this species and provides a valuable resource for identifying candidate genes involved in the biosynthesis of triterpenoid saponins and other secondary metabolites.
The immunological challenges of malaria vaccine development

Malaria remains an important public health problem throughout the tropical world causing immense human suffering and impeding economic development. Despite extensive research for > 100 years, options for preventing malaria remain limited to vector control and chemoprophylaxis. The complexity of the organism and its life cycle have, thus far, thwarted vaccine development and exacerbated the perennial problems of drug resistance. Nevertheless, development of a vaccine against malaria that reduces morbidity and mortality, and ideally also reduces transmission, has long been seen as an essential component of a sustainable malaria control strategy. In this article the authors review the biological challenges of malaria vaccine development, summarise some of the recent advances and offer some immunological insights which might facilitate further research.
Cas Endonuclease Technology—A Quantum Leap in the Advancement of Barley and Wheat Genetic Engineering

Domestication and breeding have created productive crops that are adapted to the climatic conditions of their growing regions. Initially, this process solely relied on the frequent occurrence of spontaneous mutations and the recombination of resultant gene variants. Later, treatments with ionizing radiation or mutagenic chemicals facilitated dramatically increased mutation rates, which remarkably extended the genetic diversity of crop plants. However, a major drawback of conventionally induced mutagenesis is that genetic alterations occur simultaneously across the whole genome and at very high numbers per individual plant. By contrast, the newly emerging Cas endonuclease technology allows for the induction of mutations at user-defined positions in the plant genome. In fundamental and breeding-oriented research, this opens up unprecedented opportunities for the elucidation of gene functions and the targeted improvement of plant performance. This review covers historical aspects of the development of customizable endonucleases, information on the mechanisms of targeted genome modification, as well as hitherto reported applications of Cas endonuclease technology in barley and wheat that are the agronomically most important members of the temperate cereals. Finally, current trends in the further development of this technology and some ensuing future opportunities for research and biotechnological application are presented.
Rapid ultrasensitive detection platform for antimicrobial susceptibility testing

Rapid detection and phenotyping of pathogenic microbes is critical for administration of effective antibiotic therapies and for impeding the spread of antibiotic resistance. Here, we present a novel platform, rapid ultrasensitive detector (RUSD), that utilizes the high reflectance coefficient at high incidence angles when light travels from low- to high-refractive-index media. RUSD leverages a principle that does not require complex manufacturing, labeling, or processing steps. Utilizing RUSD, we can detect extremely low cell densities (optical density [OD] ≥ 5 × 10−7) that correspond to approximately 20 bacterial cells or a single fungal cell in the detection volume, which is nearly 4 orders of magnitude more sensitive than standard OD methods. RUSD can measure minimum inhibitory concentrations (MICs) of commonly used antibiotics against gram-negative and gram-positive bacteria, including Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, within 2 to 4 h. Here, we demonstrate that antibiotic susceptibility tests for several pathogens can rapidly be performed with RUSD using both small inoculum sizes (500 cells/mL) and larger inoculum sizes (5 × 105 cells/mL) used in standard antibiotic susceptibility tests. We anticipate that the RUSD system will be particularly useful for the cases in which antibiotic susceptibility tests have to be done with a limited number of bacterial cells that are available. Its compatibility with standard antibiotic susceptibility tests, simplicity, and low cost can make RUSD a viable and rapidly deployed diagnostic tool.
Cytologic features of aggressive variants of follicular‐derived thyroid carcinoma

Certain carcinomas of the thyroid gland behave aggressively resulting in increased patient morbidity and poor patient prognosis. The diagnosis of these aggressive thyroid cancer subtypes is sometimes challenging and subject to increased interobserver variability. This review deals with the cytological features of such tumors including aggressive variants of papillary thyroid carcinoma, poorly differentiated thyroid carcinoma, and anaplastic thyroid carcinoma. These malignancies fall into 2 groups based on their cytomorphology: those that exhibit distinct microscopic features (eg, nuclear findings typical of classical papillary thyroid carcinoma or marked anaplasia) and those that present with more subtle cytologic features (eg, nuclear pseudostratification, “soap bubble” nuclei, supranuclear or subnuclear cytoplasmic vacuoles, rosette‐like structures, hobnail cells). We review the literature regarding these aggressive thyroid cancers and highlight important phenotypic characteristics that can be useful for their diagnosis based on fine needle aspiration.
Myocardial-restricted ablation of the GTPase RAD results in a pro-adaptive heart response in mice

Existing therapies to improve heart function target β-adrenergic receptor (β-AR) signaling and Ca2+ handling and often lead to adverse outcomes. This underscores an unmet need for positive inotropes that improve heart function without any adverse effects. The GTPase Ras associated with diabetes (RAD) regulates L-type Ca2+ channel (LTCC) current (ICa,L). Global RAD-knockout mice (gRAD−/−) have elevated Ca2+ handling and increased cardiac hypertrophy, but RAD is expressed also in noncardiac tissues, suggesting the possibility that pathological remodeling is due also to noncardiac effects. Here, we engineered a myocardial-restricted inducible RAD-knockout mouse (RADΔ/Δ). Using an array of methods and techniques, including single-cell electrophysiological and calcium transient recordings, echocardiography, and radiotelemetry monitoring, we found that RAD deficiency results in a sustained increase of inotropy without structural or functional remodeling of the heart. ICa,L was significantly increased, with RAD loss conferring a β-AR–modulated phenotype on basal ICa,L. Cardiomyocytes from RADΔ/Δ hearts exhibited enhanced cytosolic Ca2+ handling, increased contractile function, elevated sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2a) expression, and faster lusitropy. These results argue that myocardial RAD ablation promotes a beneficial elevation in Ca2+ dynamics, which would obviate a need for increased β-AR signaling to improve cardiac function.
Developing a dynamic HIV transmission model for 6 U.S. cities: An evidence synthesis

Background Dynamic HIV transmission models can provide evidence-based guidance on optimal combination implementation strategies to treat and prevent HIV/AIDS. However, these models can be extremely data intensive, and the availability of good-quality data characterizing regional microepidemics varies substantially within and across countries. We aim to provide a comprehensive and transparent description of an evidence synthesis process and reporting framework employed to populate and calibrate a dynamic, compartmental HIV transmission model for six US cities. Methods We executed a mixed-method evidence synthesis strategy to populate model parameters in six categories: (i) initial HIV-negative and HIV-infected populations; (ii) parameters used to calculate the probability of HIV transmission; (iii) screening, diagnosis, treatment and HIV disease progression; (iv) HIV prevention programs; (v) the costs of medical care; and (vi) health utility weights for each stage of HIV disease progression. We identified parameters that required city-specific data and stratification by gender, risk group and race/ethnicity a priori and sought out databases for primary analysis to augment our evidence synthesis. We ranked the quality of each parameter using context- and domain-specific criteria and verified sources and assumptions with our scientific advisory committee. Findings To inform the 1,667 parameters needed to populate our model, we synthesized evidence from 59 peer-reviewed publications and 24 public health and surveillance reports and executed primary analyses using 11 data sets. Of these 1,667 parameters, 1,517 (91%) were city-specific and 150 (9%) were common for all cities. Notably, 1,074 (64%), 201 (12%) and 312 (19%) parameters corresponded to categories (i), (ii) and (iii), respectively. Parameters ranked as best- to moderate-quality evidence comprised 39% of the common parameters and ranged from 56%-60% across cities for the city-specific parameters. We identified variation in parameter values across cities as well as within cities across risk and race/ethnic groups. Conclusions Better integration of modelling in decision making can be achieved by systematically reporting on the evidence synthesis process that is used to populate models, and by explicitly assessing the quality of data entered into the model. The effective communication of this process can help prioritize data collection of the most informative components of local HIV prevention and care services in order to reduce decision uncertainty and strengthen model conclusions.
Antibacterial Properties of Propolis

Researchers are continuing to discover all the properties of propolis due to its complex composition and associated broad spectrum of activities. This review aims to characterize the latest scientific reports in the field of antibacterial activity of this substance. The results of studies on the influence of propolis on more than 600 bacterial strains were analyzed. The greater activity of propolis against Gram-positive bacteria than Gram-negative was confirmed. Moreover, the antimicrobial activity of propolis from different regions of the world was compared. As a result, high activity of propolis from the Middle East was found in relation to both, Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) strains. Simultaneously, the lowest activity was demonstrated for propolis samples from Germany, Ireland and Korea.
Neuronal Encoding in a High-Level Auditory Area: From Sequential Order of Elements to Grammatical Structure

Sensitivity to the sequential structure of communication sounds is fundamental not only for language comprehension in humans but also for song recognition in songbirds. By quantifying single-unit responses, we first assessed whether the sequential order of song elements, called syllables, in conspecific songs is encoded in a secondary auditory cortex-like region of the zebra finch brain. Based on a habituation/dishabituation paradigm, we show that, after multiple repetitions of the same conspecific song, rearranging syllable order reinstated strong responses. A large proportion of neurons showed sensitivity to song context in which syllables occurred providing support for the nonlinear processing of syllable sequences. Sensitivity to the temporal order of items within a sequence should enable learning its underlying structure, an ability considered a core mechanism of the human language faculty. We show that repetitions of songs that were ordered according to a specific grammatical structure (i.e., ABAB or AABB structures; A and B denoting song syllables) led to different responses in both anesthetized and awake birds. Once responses were decreased due to song repetitions, the transition from one structure to the other could affect the firing rates and/or the spike patterns. Our results suggest that detection was based on local differences rather than encoding of the global song structure as a whole. Our study demonstrates that a high-level auditory region provides neuronal mechanisms to help discriminate stimuli that differ in their sequential structure. SIGNIFICANCE STATEMENT Sequence processing has been proposed as a potential precursor of language syntax. As a sequencing operation, the encoding of the temporal order of items within a sequence may help in recognition of relationships between adjacent items and in learning the underlying structure. Taking advantage of the stimulus-specific adaptation phenomenon observed in a high-level auditory region of the zebra finch brain, we addressed this question at the neuronal level. Reordering elements within conspecific songs reinstated robust responses. Neurons also detected changes in the structure of artificial songs, and this detection depended on local transitions between adjacent or nonadjacent syllables. These findings establish the songbird as a model system for deciphering the mechanisms underlying sequence processing at the single-cell level.
Cryptococcal Meningitis Screening and Community-based Early Adherence Support in People With Advanced Human Immunodeficiency Virus Infection Starting Antiretroviral Therapy in Tanzania and Zambia: A Cost-effectiveness Analysis

Abstract Background A randomized trial demonstrated that among people living with late-stage human immunodeficiency virus (HIV) infection initiating antiretroviral therapy, screening serum for cryptococcal antigen (CrAg) combined with adherence support reduced all-cause mortality by 28%, compared with standard clinic-based care. Here, we present the cost-effectiveness. Methods HIV-infected adults with CD4 count <200 cells/μL were randomized to either CrAg screening plus 4 weekly home visits to provide adherence support or to standard clinic-based care in Dar es Salaam and Lusaka. The primary economic outcome was health service care cost per life-year saved as the incremental cost-effectiveness ratio (ICER), based on 2017 US dollars. We used nonparametric bootstrapping to assess uncertainties and univariate deterministic sensitivity analysis to examine the impact of individual parameters on the ICER. Results Among the intervention and standard arms, 1001 and 998 participants, respectively, were enrolled. The annual mean cost per participant in the intervention arm was US$339 (95% confidence interval [CI], $331–$347), resulting in an incremental cost of the intervention of US$77 (95% CI, $66–$88). The incremental cost was similar when analysis was restricted to persons with CD4 count <100 cells/μL. The ICER for the intervention vs standard care, per life-year saved, was US$70 (95% CI, $43–$211) for all participants with CD4 count up to 200 cells/μL and US$91 (95% CI, $49–$443) among those with CD4 counts <100 cells /μL. Cost-effectveness was most sensitive to mortality estimates. Conclusions Screening for cryptococcal antigen combined with a short period of adherence support, is cost-effective in resource-limited settings.