Miracle-dz/UniFAR-FTUs huggingface dataset:
National trends in emergency department closures, mergers, and utilization, 2005-2015

Study objectives To describe nationwide hospital-based emergency department (ED) closures and mergers, as well as the utilization of emergency departments and inpatient beds, over time and across varying geographic areas in the United States. Methods Observational analysis of the American Hospital Association (AHA) Annual Survey from 2005 to 2015. Primary outcomes were hospital-based ED closure and merger. Secondary outcomes were yearly ED visits per hospital-based ED and yearly hospital admissions per hospital bed. Results The total number of hospital-based EDs decreased from 4,500 in 2005 to 4,460 in 2015, with 200 closures, 138 mergers, and 160 new hospital-based EDs. While yearly ED visits per hospital-based ED exhibited a 28.6% relative increase (from 25,083 to 32,248), yearly hospital admissions per hospital bed had a 3.3% relative increase (from 45.4 to 43.9) from 2005 to 2015. The number of hospital admissions and hospital beds did not change significantly in urban areas and declined in rural areas. ED visits grew more uniformly across urban and rural areas. Conclusions The number of hospital-based ED closures is small when accounting for mergers, but occurs as many more patients are presenting to a stable number of EDs in larger health systems, though rural areas may differentially affected. EDs were managing accelerating patient volumes alongside stagnant inpatient bed capacity.
Evaluation of gait outcomes for individuals with established unilateral transfemoral amputation following the provision of microprocessor controlled knees in the context of a clinical service

Background: Microprocessor controlled knees (MPKs) have been shown to improve gait outcomes for individuals with unilateral transfemoral amputation (TFA); however, previous studies have limitations, which may affect their applicability. Objectives: To compare gait outcomes between non-MPK and MPK conditions within a large and diverse cohort of established TFAs in the pragmatic context of an operational clinical service and to identify any demographic variables that correlate with changes in gait outcomes. Study Design: This is a retrospective cohort study. Methods: Full-body three-dimensional motion capture and a portable breath gas analyser were used to evaluate gait-specific outcomes both pre-MPK and 6 months post-MPK provisions in TFAs (n = 32). The primary outcome measure was gait profile score, along with the following secondary outcome measures: walking velocity, step length, step length symmetry ratio, step time symmetry ratio, vertical ground reaction force symmetry index, base of support, center of mass deviation, and oxygen cost of walking. Results: Data showed statistically significant improvement in gait profile score from 11.2° ± 2.2° to 10.1° ± 2.1° (p < 0.01) between non-MPK and MPK conditions. Other outcomes which showed significant improvement were walking velocity (p < 0.01), step length (p < 0.01), vertical ground reaction force symmetry index (p < 0.01), and center of mass deviation (p < 0.05). Conclusions: MPK provision offered significant gait improvements to this cohort of TFAs in an operational clinical setting. There still remains a large gap in gait outcomes between this cohort and those of healthy unimpaired adults. Improvements in socket design, prosthetic foot design, and physiotherapy intervention could further reduce this gap.
Microevolution in the pansecondary metabolome of Aspergillus flavus and its potential macroevolutionary implications for filamentous fungi

Significance Secondary metabolites (SMs) produced by fungi mediate ecological interactions, define fungal niches, and are of profound pharmacological importance to humans. Most work on SMs has focused on a small number of individuals from each species, not fully reflecting the importance of intraspecific diversity. We demonstrate that even in one of the best-studied model fungi, the carcinogen-producing Aspergillus flavus, more than 25% of SM-producing biosynthetic gene clusters (BGCs) are novel and/or show population-specific variants. These results support the finding that the organization of BGC diversity into population-specific patterns may sometimes result from ecologically important interactions and may inform evolutionary and etiological inferences of SM capacities within a species. Importantly, our work also presents a vision of sources of potential pharmaceuticals. Fungi produce a wealth of pharmacologically bioactive secondary metabolites (SMs) from biosynthetic gene clusters (BGCs). It is common practice for drug discovery efforts to treat species’ secondary metabolomes as being well represented by a single or a small number of representative genomes. However, this approach misses the possibility that intraspecific population dynamics, such as adaptation to environmental conditions or local microbiomes, may harbor novel BGCs that contribute to the overall niche breadth of species. Using 94 isolates of Aspergillus flavus, a cosmopolitan model fungus, sampled from seven states in the United States, we dereplicate 7,821 BGCs into 92 unique BGCs. We find that more than 25% of pangenomic BGCs show population-specific patterns of presence/absence or protein divergence. Population-specific BGCs make up most of the accessory-genome BGCs, suggesting that different ecological forces that maintain accessory genomes may be partially mediated by population-specific differences in secondary metabolism. We use ultra-high-performance high-resolution mass spectrometry to confirm that these genetic differences in BGCs also result in chemotypic differences in SM production in different populations, which could mediate ecological interactions and be acted on by selection. Thus, our results suggest a paradigm shift that previously unrealized population-level reservoirs of SM diversity may be of significant evolutionary, ecological, and pharmacological importance. Last, we find that several population-specific BGCs from A. flavus are present in Aspergillus parasiticus and Aspergillus minisclerotigenes and discuss how the microevolutionary patterns we uncover inform macroevolutionary inferences and help to align fungal secondary metabolism with existing evolutionary theory.
Learning where to trust unreliable models in an unstructured world for deformable object manipulation

We plan for rope manipulation with an unreliable model by learning where to trust the model and how to recover when stuck. The world outside our laboratories seldom conforms to the assumptions of our models. This is especially true for dynamics models used in control and motion planning for complex high–degree of freedom systems like deformable objects. We must develop better models, but we must also consider that, no matter how powerful our simulators or how big our datasets, our models will sometimes be wrong. What is more, estimating how wrong models are can be difficult, because methods that predict uncertainty distributions based on training data do not account for unseen scenarios. To deploy robots in unstructured environments, we must address two key questions: When should we trust a model and what do we do if the robot is in a state where the model is unreliable. We tackle these questions in the context of planning for manipulating rope-like objects in clutter. Here, we report an approach that learns a model in an unconstrained setting and then learns a classifier to predict where that model is valid, given a limited dataset of rope-constraint interactions. We also propose a way to recover from states where our model prediction is unreliable. Our method statistically significantly outperforms learning a dynamics function and trusting it everywhere. We further demonstrate the practicality of our method on real-world mock-ups of several domestic and automotive tasks.
ROBBER FLIES (DIPTERA: ASILIDAE) AS PREDATORS OF HARVESTER ANT WORKERS (HYMENOPTERA: FORMICIDAE: POGONOMYRMEX) IN EASTERN NEW MEXICO AND WEST TEXAS

Abstract Three species of robber flies (Asilidae) are recorded as preying on workers of Pogonomyrmex harvester ants in eastern New Mexico and western Texas: Cerotainiops abdominalis, Saropogon combustus, and Saropogon pritchardi. Of 379 prey records for C. abdominalis, 66% were Pogonomyrmex workers. Two species of Saropogon were collected in association with a large number of harvester ant workers: S. combustus (40% of 263 prey records) and S. pritchardi (94% of 288 prey records). All three species show a statistical preference for Hymenoptera, specifically for harvester ant workers, and avoidance of Diptera, Hemiptera, Lepidoptera, and Orthoptera prey. A brief review of invertebrate predators of Pogonomyrmex workers is given, with emphasis on asilid predators. For the three asilid predators mentioned in the article, seasonality, observed behaviors, and a list of known prey taxa are included.
Functional coordination of BET family proteins underlies altered transcription associated with memory impairment in fragile X syndrome

The coordination of BET family proteins is a feature of the gene regulatory network underlying memory behavior and FXS. Bromodomain and extraterminal proteins (BET) are epigenetic readers that play critical roles in gene regulation. Pharmacologic inhibition of the bromodomain present in all BET family members is a promising therapeutic strategy for various diseases, but its impact on individual family members has not been well understood. Using a transcriptional induction paradigm in neurons, we have systematically demonstrated that three major BET family proteins (BRD2/3/4) participated in transcription with different recruitment kinetics, interdependency, and sensitivity to a bromodomain inhibitor, JQ1. In a mouse model of fragile X syndrome (FXS), BRD2/3 and BRD4 showed oppositely altered expression and chromatin binding, correlating with transcriptional dysregulation. Acute inhibition of CBP/p300 histone acetyltransferase (HAT) activity restored the altered binding patterns of BRD2 and BRD4 and rescued memory impairment in FXS. Our study emphasizes the importance of understanding the BET coordination controlled by a balanced action between HATs with different substrate specificity.
Genome-scale CRISPR-Cas9 screen of Wnt/β-catenin signaling identifies therapeutic targets for colorectal cancer

Genome-scale CRISPR screen identifies KMT2A as a druggable target against Wnt/β-catenin signaling and colorectal cancer. Aberrant activation of Wnt/β-catenin pathway is a key driver of colorectal cancer (CRC) growth and of great therapeutic importance. In this study, we performed comprehensive CRISPR screens to interrogate the regulatory network of Wnt/β-catenin signaling in CRC cells. We found marked discrepancies between the artificial TOP reporter activity and β-catenin–mediated endogenous transcription and redundant roles of T cell factor/lymphoid enhancer factor transcription factors in transducing β-catenin signaling. Compiled functional genomic screens and network analysis revealed unique epigenetic regulators of β-catenin transcriptional output, including the histone lysine methyltransferase 2A oncoprotein (KMT2A/Mll1). Using an integrative epigenomic and transcriptional profiling approach, we show that KMT2A loss diminishes the binding of β-catenin to consensus DNA motifs and the transcription of β-catenin targets in CRC. These results suggest that KMT2A may be a promising target for CRCs and highlight the broader potential for exploiting epigenetic modulation as a therapeutic strategy for β-catenin–driven malignancies.
Weighting tumor-specific TCR repertoires as a classifier to stratify the immunotherapy delivery in non–small cell lung cancers

TIR index is a feasible approach for assessing tumor-specific TCR and stratifying NSCLC patients for anti-PD-(L)1 therapy. Analysis of T cell receptor (TCR) repertoires may contribute to better understanding of the response to immunotherapy. By deep sequencing of the TCR β chain complementarity-determining regions in the paired biopsies and peripheral blood specimens of 31 patients with non–small cell lung cancer (NSCLC) treated with anti–programmed death 1 (PD-1) or PD-ligand 1 (PD-L1) therapy, we developed a previously unidentified index, the TCR-based immunotherapy response index (TIR index), that estimated the degree of overlap of the TCR repertoire between tumor-infiltrating lymphocytes and circulating PD-1+CD8+T cells (shared TCR clones). This index correlated with response and survival outcomes of anti–PD-(L)1 treatment. All the TCR sequences of neoantigen-stimulated T cells were included in the shared TCR clones, indicating that TCR clones involved in TIR index estimation represented tumor-specific T cells. Therefore, the TIR index is a feasible approach for assessing tumor-specific TCR and stratifying patients with NSCLC for anti–PD-(L)1 therapy.
Zeb1 induces immune checkpoints to form an immunosuppressive envelope around invading cancer cells

Zeb1-induced immune checkpoints promote M2 macrophages and protect invading lung cancer cells from inflammatory cells. The PDL1-PD1 immune checkpoint inhibits T cell activation, and its blockade is effective in a subset of patients. Studies are investigating how checkpoints are hijacked by cancer cells and why most patients remain resistant to immunotherapy. Epithelial mesenchymal transition (EMT), which drives tumor cell invasion via the Zeb1 transcription factor, is linked to immunotherapy resistance. In addition, M2-polarized tumor-associated macrophages (TAMs), which inhibit T cell migration and activation, may also cause immunotherapy resistance. How EMT in invading cancer cells is linked to therapy resistance and events driving TAM M2 polarization are therefore important questions. We show that Zeb1 links these two resistance pathways because it is required for PDL1 expression on invading lung cancer cells, and it also induces CD47 on these invading cells, which drives M2 polarization of adjacent TAMs. Resulting reprogramming of the microenvironment around invading cells shields them from the hostile inflammatory environment surrounding tumors.
A flexible multiplexed immunosensor for point-of-care in situ wound monitoring

An integrated smart microfluidic dressing with a multibiomarker immunosensor can provide in situ wound status profiling on site. Chronic wounds arise from interruption of normal healing due to many potential pathophysiological factors. Monitoring these multivariate factors can provide personalized diagnostic information for wound management, but current sensing technologies use complex laboratory tests or track a limited number of wound parameters. We report a flexible biosensing platform for multiplexed profiling of the wound microenvironment, inflammation, and infection state at the point of care. This platform integrates a sensor array for measuring inflammatory mediators [tumor necrosis factor–α, interleukin-6 (IL-6), IL-8, and transforming growth factor–β1], microbial burden (Staphylococcus aureus), and physicochemical parameters (temperature and pH) with a microfluidic wound exudate collector and flexible electronics for wireless, smartphone-based data readout. We demonstrate in situ multiplexed monitoring in a mouse wound model and also profile wound exudates from patients with venous leg ulcers. This technology may facilitate more timely and personalized wound management to improve chronic wound healing outcomes.
Comparative analysis on bioactive compounds and antioxidant activity of Algerian fenugreek (Trigonella foenum-graecum L.) and Syrian cumin (Cuminum cyminum L.) seeds

Summary Introduction: Natural products represent a gold mine for scientists looking for compounds for the treatment of health problems and diseases with their different biological and pharmacological activities. However, recent research is focused on finding natural sources of antioxidants. Objective: The objective of current research was to determine the phytochemical profile of Algerian fenu-greek (Trigonella foenum-graecum L.), and Syrian cumin (Cuminum cyminum L.) seeds in order to characterize their phenolic compounds and to determine their antioxidant activities. Methods: Total phenolic, flavonoids, condensed and hydrolysable tannins contents were quantified using Folin-Ciocalteu, aluminium chloride, vanillin and ferric chloride methods, respectively. Phenolic compounds were identified by HPLC method and antioxidant activity was measured using DPPH assay. Results: The higher amounts of total phenolic compounds, flavonoids, condensed and hydrolysable tannins were given by fenugreek. Results of HPLC analysis of our plants showed that eight phytochemical compounds were found in cumin extract, and seven molecules in fenugreek extract. Moreover, fenugreek possessed higher antioxidant activity. Conclusion: This study confirmed that our plants are a good source of phenolic contents and possess a high antioxidant activity.
Sublingual immunotherapy increases Treg/Th17 ratio in allergic rhinitis

Abstract Background Few studies investigated the effects of sublingual immunotherapy (SLIT) on the peripheral regulatory T cells (Tregs)/Th17 ratio. Objective To investigate the effectiveness of SLIT in children with allergic rhinitis (AR) and the effects on the Tregs/Th17 ratio. Methods This was a retrospective study of children who were treated for AR between April 2017 and March 2018 at one hospital. The patients were grouped according to the treatments they received: SLIT + pharmacotherapy vs pharmacotherapy alone. Results Eighty children (51 boys and 29 girls; 40/group) were included. The visual analog scale (VAS) and medication scores at 1 year in the SLIT + pharmacotherapy group were 2.70 ± 1.08 and 1.1 ± 0.8, respectively, which were lower than at baseline (7.7 ± 1.2 and 3.6 ± 1.0, respectively) (both Ps < 0.05). For the pharmacotherapy group, the VAS score was decreased at 1 year vs baseline (3.3 ± 1.2 vs 7.4 ± 1.0; P < 0.05), but the medication score did not change (P > 0.05). In the SLIT + pharmacotherapy group, the Treg percentage increased, while the Th17 percentage decreased at 1 year (both Ps < 0.01). The percentages of Tregs and Th17s did not change in the pharmacotherapy group (both Ps > 0.05). Conclusions SLIT + pharmacotherapy can increase the Treg percentage and decrease the Th17 percentage in the peripheral blood of children with AR.
Chemical composition of dried Stevia rebaudiana Bertoni leaves and effect of ultrasound-assisted extraction on total steviosides content in extract

Summary Introduction: Steviol stevioside, which has been used in the production of food products as a low-calorie sweeten, is one of the main glycoside groups in the leaves of the Stevia plants. It is useful for human health. Objective: The main objection of the present study was to find out some major chemical compositions of the dried Stevia rebaudiana Bertoni leaves and an effective, affordable, and environmentally friendly method to reach the high extraction yield of total steviosides from them. Therefore, a novel extraction, ultrasound-assisted extraction (UAE), was carried out to extract total steviosides from dried leaves of S. rebaudiana plant with ethanol of 70% (v/v) as a solvent. Methods: Some major chemical compositions of the dried S. rebaudiana leaves were analyzed according to the AOAC (Association of Official Analytical Chemists) and total steviosides content (TSC) was measured by anthrone-sulphuric acid colorimetric assay with main influencing factors including material/solvent ratio, extraction temperature, and extraction time. Results: The results referred that some chemical compounds such as protein, lipid, fibre, sugar, etc. existed in this material. The best extraction conditions were the sample/solvent ratio of 1:100 (g/ml), extraction temperature of 75oC, and extraction time of 30 min. Conclusion: The highest amount of total steviosides content of 8.894 % was obtained at the optimal extraction condition. Consequently, these results demonstrated that the parameters of UAE were applied successfully for producing total glycosides.
Environmental History of Rice Plantations in the Early Modern Ottoman Empire Between the 15th And 19th Centuries and Its Potential for Climate Research

Abstract Historians readily discuss the effect of climate change on the 21st century, but Ottomanists rarely reference palaeoclimatology data. This research compares palaeoclimatological data with documentary evidence from institutionalized rice plantations in the Ottoman Empire. Between the 15th and 19th centuries, the empire employed a group of experts for the cultivation of rice in the vast region between the Tigris and the Danube. Extensive registers exist from this period in archives that give documentary evidence about the organization of plantations, yields, prices and destructive floods. The objective of the study, as presented in this article, is to find rice-related phenological data in Ottoman Archive registers. It utilizes a comparative analysis of the Old World Drought Atlas (OWDA) summer precipitation data reconstructed by Cook et al. (2015), temperature changes, documentary evidence about seasonal extremes and archival evidence. The comparison shows that palaeoclimatology proxies are important sources of information regarding changes in rice cultivation. It also indicates that the Ottoman archive is a valuable source of possible phenological data. Thus, research sources from nature and societies complement one another. The comparison also demonstrates that climate change during the Ottoman Empire’s reign showed regional differences, and a local comparison of phenological data and palaeoclimatological data can explain more about the effects of the Little Ice Age (LIA) on the empire.
The Potential Use of Osl Properties of Quartz in Investigating Fluvial Processes on the Catchment of River Mureş, Romania

Abstract To understand the functioning of fluvial systems it is important to investigate dynamics of sediment transport and the source of sediments. In case of reconstructing past processes these studies must be accompanied by the numerical dating of sediment samples. In this respect optically stimulated luminescence is a widely used technique, by which the time of sediment deposition can be directly dated. Recently, in various fluvial environments it has been shown that certain luminescence properties of minerals, and especially that of quartz, can be applied as indicators of fluvial erosion and/or sediment provenance. These properties are residual luminescence (or residual dose) and luminescence sensitivity of quartz grains. However, the values of the parameters above are affected by various factors, the importance of which is under debate. The present study therefore aims to assess these factors along a ~560 km long reach of River Mureş (Maros) a relatively large river with a compound surface lithology on its catchment. The research focused on the sandy fraction of modern sediments, collected from the main river and from three tributaries alike. This way not only longitudinal downstream changes, but the influence of tributaries could also be studied. Based on the data, both investigated parameters show a great variation, which can be attributed to the lithological differences of subcatchments and geomorphological drivers, such as erosional activity and potential number of sedimentary cycles, and human activity. However, relationships are not entirely clear and are influenced by the maximum grain size of the samples investigated, and the recycling of previously laid deposits with different properties. Still, when performing detailed dating studies, and tracing sediments from certain parts of the catchment luminescence properties can be a useful tool in the future.