Miracle-dz/UniFAR-FTUs huggingface dataset:
Concentration-dependent Early Antivascular and Antitumor Effects of Itraconazole in Non–Small Cell Lung Cancer

Purpose: Itraconazole has been repurposed as an anticancer therapeutic agent for multiple malignancies. In preclinical models, itraconazole has antiangiogenic properties and inhibits Hedgehog pathway activity. We performed a window-of-opportunity trial to determine the biologic effects of itraconazole in human patients. Experimental Design: Patients with non–small cell lung cancer (NSCLC) who had planned for surgical resection were administered with itraconazole 300 mg orally twice daily for 10–14 days. Patients underwent dynamic contrast-enhanced MRI and plasma collection for pharmacokinetic and pharmacodynamic analyses. Tissues from pretreatment biopsy, surgical resection, and skin biopsies were analyzed for itraconazole and hydroxyitraconazole concentration, and vascular and Hedgehog pathway biomarkers. Results: Thirteen patients were enrolled in this study. Itraconazole was well-tolerated. Steady-state plasma concentrations of itraconazole and hydroxyitraconazole demonstrated a 6-fold difference across patients. Tumor itraconazole concentrations trended with and exceeded those of plasma. Greater itraconazole levels were significantly and meaningfully associated with reduction in tumor volume (Spearman correlation, −0.71; P = 0.05) and tumor perfusion (Ktrans; Spearman correlation, −0.71; P = 0.01), decrease in the proangiogenic cytokines IL1b (Spearman correlation, −0.73; P = 0.01) and GM-CSF (Spearman correlation, −1.00; P < 0.001), and reduction in tumor microvessel density (Spearman correlation, −0.69; P = 0.03). Itraconazole-treated tumors also demonstrated distinct metabolic profiles. Itraconazole treatment did not alter transcription of GLI1 and PTCH1 mRNA. Patient size, renal function, and hepatic function did not predict itraconazole concentrations. Conclusions: Itraconazole demonstrates concentration-dependent early antivascular, metabolic, and antitumor effects in patients with NSCLC. As the number of fixed dose cancer therapies increases, attention to interpatient pharmacokinetics and pharmacodynamics differences may be warranted.
Cost-effectiveness of the COPD Patient Management European Trial home-based disease management program

Purpose Efficient management of COPD represents an international challenge. Effective management strategies within the means of limited health care budgets are urgently required. This analysis aimed to evaluate the cost-effectiveness of a home-based disease management (DM) intervention vs usual management (UM) in patients from the COPD Patient Management European Trial (COMET). Methods Cost-effectiveness was evaluated in 319 intention-to-treat patients over 12 months in COMET. The analysis captured unplanned all-cause hospitalization days, mortality, and quality-adjusted life expectancy. Costs were evaluated from a National Health Service perspective for France, Germany, and Spain, and in a pooled analysis, and were expressed in 2015 Euros (EUR). Quality of life was assessed using the 15D health-related quality-of-life instrument and mapped to utility scores. Results Home-based DM was associated with improved mortality and quality-adjusted life expectancy. DM and UM were associated with equivalent direct costs (DM reduced costs by EUR −37 per patient per year) in the pooled analysis. DM was associated with lower costs in France (EUR −806 per patient per year) and Spain (EUR −51 per patient per year), but higher costs in Germany (EUR 391 per patient per year). Evaluation of cost per death avoided and cost per quality-adjusted life year (QALY) gained showed that DM was dominant (more QALYs and cost saving) in France and Spain, and cost-effective in Germany vs UM. Nonparametric bootstrapping analysis, assuming a willingness-to-pay threshold of EUR 20,000 per QALY gained, indicated that the probability of home-based DM being cost-effective vs UM was 87.7% in France, 81.5% in Spain, and 75.9% in Germany. Conclusion Home-based DM improved clinical outcomes at equivalent cost vs UM in France and Spain, and in the pooled analysis. DM was cost-effective in Germany with an incremental cost-effectiveness ratio of EUR 2,541 per QALY gained. The COMET home-based DM intervention could represent an attractive alternative to UM for European health care payers.
Osteopathic Manipulative Treatment for a Recognizable Pattern of Somatic Dysfunction Following Laparoscopic Cholecystectomy

Abstract Context Previous literature has demonstrated the prevalence and socioeconomic impact of postoperative pain in surgery patients. Somatic dysfunction has been demonstrated as a cause, but literature documenting osteopathic manipulative treatment (OMT) in surgery patients is lacking. Objective To describe typical patterns of and common treatments for somatic dysfunction in patients following laparoscopic cholecystectomy. Methods The authors retrospectively reviewed the billing records of all patients over 18 years of age who underwent laparoscopic cholecystectomy by a single surgeon and had postoperative outpatient OMT for right-side pain linked to somatic dysfunction between 2006 and 2018 at a community hospital in Grand Rapids, Michigan. Patients who underwent open cholecystectomy, who did not have documented somatic dysfunction, or had somatic dysfunction unrelated to their biliary disease were excluded. Results Nine patients were selected for inclusion in this retrospective case series. All patients in the study demonstrated anterior right lower rib pain corresponding to posterior lower rib dysfunctions and rotated right and side-bent left thoracic spine dysfunctions between T5 and T11. Pain was successfully managed with muscle energy, high-velocity, low-amplitude, or soft tissue OMT. Conclusion Postoperative pain following laparoscopic cholecystectomy can be related to right-sided thoracic and rib dysfunctions. This is important for early diagnosis of surgical patients with somatic dysfunction and initiation of appropriate OMT to decrease morbidity related to pain, functional status, and quality of life.
Multidrug-Resistant Candida auris Infections in Critically Ill Coronavirus Disease Patients, India, April–July 2020

In New Delhi, India, candidemia affected 15 critically ill coronavirus disease patients admitted to an intensive care unit during April–July 2020. Candida auris accounted for two thirds of cases; case-fatality rate was high (60%). Hospital-acquired C. auris infections in coronavirus disease patients may lead to adverse outcomes and additional strain on healthcare resources.
Does the biogeographic origin of species matter? Ecological effects of native and non‐native species and the use of origin to guide management

The introduction and success of non‐native species are both a consequence and a cause of rapid global change. Humans have created novel ecosystems through environmental modification and mass movements of organisms around the planet. It has been argued that species biogeographic origin cannot explain or predict ecological impacts and the origin of a species should not influence ecosystem management. This rejection of ‘origin’ is overly simplistic. Origin effects can arise through biased sampling of the types of species transported, the environmental and evolutionary context of their source environments and the communities and environments to which they are introduced. Differences in co‐evolutionary histories between source and recipient environments, and adaptation of introduced species to modified environmental conditions, can also shape origin effects. The high rates and long distances of human‐mediated dispersal have increased the sizes of regional species pools. In addition, human transported, non‐native species can change the function of recipient ecosystems through changes to community composition. We outline how origin effects can cascade through to ecological impact at population, community and ecosystem levels. Synthesis. Non‐native species can have predictable and preventable effects on recipient communities. We identify multiple sources of origin effects and describe the ecological and evolutionary pathways through which origin effects lead to impacts. This functional understanding of origin effects must include human actions. However, species origin should not, on its own, be used as a shortcut for management decisions; origin effects should instead feed into a process whereby ecologists work together with managers, policymakers and broader society to guide decisions on how to respond to the effects of non‐native species.
Construction of Pseudomolecules for the Chinese Chestnut (Castanea mollissima) Genome

The Chinese chestnut (Castanea mollissima Bl.) is a woody nut crop with a high ecological value. Although many cultivars have been selected from natural seedlings, elite lines with comprehensive agronomic traits and characters remain rare. To explore genetic resources with aid of whole genome sequence will play important roles in modern breeding programs for chestnut. In this study, we generated a high-quality C. mollissima genome assembly by combining 90× Pacific Biosciences long read and 170× high-throughput chromosome conformation capture data. The assembly was 688.93 Mb in total, with a contig N50 of 2.83 Mb. Most of the assembled sequences (99.75%) were anchored onto 12 chromosomes, and 97.07% of the assemblies were accurately anchored and oriented. A total of 33,638 protein-coding genes were predicted in the C. mollissima genome. Comparative genomic and transcriptomic analyses provided insights into the genes expressed in specific tissues, as well as those associated with burr development in the Chinese chestnut. This highly contiguous assembly of the C. mollissima genome provides a valuable resource for studies aiming at identifying and characterizing agronomical-important traits, and will aid the design of breeding strategies to develop more focused, faster, and predictable improvement programs.
Sensory and Physicochemical Characterization of Sourdough Bread Prepared with a Coconut Water Kefir Starter

There is a recognized need for formulating functional food products using selected lactic acid bacteria (LAB) starter cultures from various sources such as kefir, yoghurt or kombucha that have health benefits. The principle objective of this study was to investigate the use of a coconut water kefir-based fermentation starter culture using Lactobacillus fermentum and Lactobacillus plantarum to develop a sourdough bread. Check-all-that-apply (CATA) sensory profiling was used in this study to evaluate the sensory profile of sourdough breads that varied with culture type, culture concentrations, with and without added yeast, and with fermentation for 18 and 24 h. Based on correspondence analysis (CA) of the CATA results, bread samples with positive sensory attributes were chosen for further physicochemical analysis. Physicochemical analyses (texture, proximate composition, shelf life, carboxylic acid analysis and amino acid analysis) were carried out on breads formulated with starter culture concentrations of 8.30 log CFU/mL of L. fermentum, 4.90 log CFU/mL of L. fermentum and 9.60 log CFU/mL of L. plantarum, each fermented for 24 h without baker’s yeast. The bread sample that was formulated with a coconut water kefir (CWK) starter culture containing 9.60 log CFU/mL of L. plantarum, without dry yeast and fermented for 24 h, had significantly higher values for almost all amino acids and a lower protein content compared to samples formulated using CWK cultures containing 8.30 log CFU/mL of L. fermentum and 4.90 log CFU/mL of L. fermentum, both without dry yeast and fermented for 24 h. The bread sample formulated with CWK starter culture containing 9.60 log CFU/mL of L. plantarum, without dry yeast and fermented for 24 h, also produced significant quantities of organic acids (pyruvic acid, acetic acid, lactic acid and succinic acid). These changes in the physicochemical properties can improve overall bread quality in terms of flavor, shelf life, texture and nutritional value.
An Efficient Soft Output MIMO Detector Architecture Considering High-order Modulations

In this paper, we investigate soft-output K-best and fixed-complexity sphere decoder (FSD) detectors for multiple-input multiple-output (MIMO) systems, where high-order mod-ulations are considered. When using the conventional parallel candidate adding aided (PCA-aided) soft-output algorithm, the FSD and K-Best detectors provide similar bit error rate (BER) performances. In contrast, when using the proposed candidate-list-aided soft-output algorithm, the FSD detector outperforms the K-best detector and delivers a near-ML (maximum likelihood) performance. Therefore, a soft-output FSD detector architecture, which guarantees a feasible implementation complexity level, is devised for the MIMO system which consider large-scale antennas and modulation orders. Compared to the works reported in liter-ature, the proposed detector is able to provide a notably enhanced error performance with feasible implementation complexity.
Effects of whole raw soybean or whole cottonseed on milk yield and composition, digestibility, ruminal fermentation and blood metabolites of lactating dairy cows

The aim of the present study was to evaluate effects of partial replacement of corn grain and soybean meal with whole raw soybean or whole cottonseed on milk yield and composition, digestibility, ruminal fermentation and blood metabolites. Eighteen multiparous Holstein cows (133.0 ± 53.1 days in milk, 585.2 ± 54.2 kg of BW and 32.22 ± 5.32 kg/day of milk) were used in six 3 × 3 Latin squares with 21-day periods. The cows were randomly assigned to receive one of the following diets: control (CT), diet without oilseed inclusion; whole soybean (WS), inclusion of 120 g/kg of whole raw soybean (diet DM basis); and whole cottonseed (WCS), inclusion of 120 g/kg of whole cottonseed (diet DM basis). Dietary supplementation with WS or WCS had no effect on milk yield and composition. DM and non-fibre carbohydrate intake were decreased in cows fed WS and WCS when compared with CT; however, WS and WCS increased ether extract intake and digestibility. The WCS decreased DM, crude protein, ether extract and non-fibre carbohydrate intake when compared with WS. Cows fed WCS had higher ruminal pH than those fed WS or CT. Cows fed WS showed higher propionate concentration than cows fed WCS. Ruminal ammonia nitrogen concentration decreased when cows were fed WS compared with those fed CT or WCS. The partial replacement of corn grain and soybean meal with WS or WCS in diets of mid-lactating dairy cows decreased DM intake and altered ruminal fermentation, but did not affect milk yield and composition.
Evaluation of Cysteine Protease C of Leishmania donovani in Comparison with Glycoprotein 63 and Elongation Factor 1α for Diagnosis of Human Visceral Leishmaniasis and for Posttreatment Follow-Up Response

Visceral leishmaniasis (VL) is a threat in many developing countries. Much effort has been put to eliminating this disease, for which serodiagnosis remains the mainstay for VL control programs. New and improved antigens as diagnostic candidates are required, though, as the available antigens fail to demonstrate equal optimum performance in all areas of endemicity. Moreover, these diagnoses are dependent on invasive serum sampling. In the current study, we cloned and expressed Leishmania donovani cysteine protease C (CPC) and evaluated its diagnostic and test-of-cure possibilities by detecting the antibody levels in human serum and urine through ELISA and immunoblot assays. ABSTRACT Visceral leishmaniasis (VL) is a threat in many developing countries. Much effort has been put to eliminating this disease, for which serodiagnosis remains the mainstay for VL control programs. New and improved antigens as diagnostic candidates are required, though, as the available antigens fail to demonstrate equal optimum performance in all areas of endemicity. Moreover, these diagnoses are dependent on invasive serum sampling. In the current study, we cloned and expressed Leishmania donovani cysteine protease C (CPC) and evaluated its diagnostic and test-of-cure possibilities by detecting the antibody levels in human serum and urine through ELISA and immunoblot assays. Two immunodominant antigens, recombinant glycoprotein 63 (GP63) and elongation factor 1α (EF1α), identified earlier by our group, were also assessed by employing human serum and urine samples. Of these three antigens in ELISAs, CPC demonstrated the highest sensitivities of 98.15% and 96% positive testing in serum and urine of VL patients, respectively. Moreover, CPC yielded 100% specificity with serum and urine of nonendemic healthy controls compared to GP63 and EF1α. Urine samples were found to be more specific than serum for distinguishing endemic healthy controls and other diseases by means of all three antigens. In all cases, CPC gave the most promising results. Unlike serum, urine tests demonstrated a significant decrease in antibody levels for CPC, GP63, and EF1α after 6 months of treatment. The diagnostic and test-of-cure performances of CPC in the immunoblot assay were found to be better than those of GP63 and EF1α. In conclusion, CPC, followed by GP63 and EF1α, may be utilized as candidates for diagnosis of VL and to assess treatment response.
Life history and production of above- and belowground structures of Cladium mariscoides (Muhl.) Torr. in a western New York fen

BERNARD, J. M. , F. K. SEISCHAB AND GAIL JACOBY (Dept. Biol., Ithaca College, Ithaca, NY 14850 and Dept. Biol. Rochester Inst. Tech., Rochester, NY 14623-0887). Life history and production of above and belowground structures of Cladium mariscoides (Muhl.) Torr. in a western New York fen. Bull. Torrey Bot. Club 112:288-294. 1985. -Seasonal changes in numbers and weights were determined for three categories of shoots aboveground and root and rhizome weights belowground. Total shoot numbers were over 1000/M2 in May, evenly divided between old and young categories. From late June to mid-September they averaged approximately 750-800/M2 with declining numbers of old and young but increasing numbers of newly emerged shoots. Shoot standing crop reached a maximum of 224 g/m2 in late August, most of the total contributed by young shoots. Aboveground production is estimated to be 227.6 g/m2/yr. Belowground root and rhizome standing crops reached a maximum of 68 and 51 g/m2 respectively and we estimate their annual production to be approximately 47 g/m2/ year (27.7 g/m2/year roots; 19.3 g/m2/year rhizomes). Live root/live shoot ratios ranged from 0.8-1.0.
Review of Orbitofrontal Cortex in Alcohol Dependence: A Disrupted Cognitive Map?

Alcoholism is a persistent worldwide problem associated with long-lasting impairments to decision-making processes. Some aspects of dysfunction are thought to reflect alcohol-induced changes to relevant brain areas such as the orbitofrontal cortex (OFC). In this review, we will examine how chronic alcohol exposure alters OFC function to potentially contribute to maladaptive decision-making, and explore experimental behavioral approaches that may be better suited to test whether alcohol dependence disrupts OFC's function. We argue that although past works suggest impairments in aspects of OFC function, more information may be gained by specifically targeting tasks to the broader function of OFC as put forth by the recent hypothesis of OFC as a "cognitive map" of task space. Overall, we suggest that such a focus could provide a better understanding of how OFC function changes in alcohol dependence, and could inform better assessment tools and treatment options for clinicians working with this population.
The Efficacy of Hypotensive Agents on Intraoperative Bleeding and Recovery Following General Anesthesia for Nasal Surgery: A Network Meta-Analysis

Objectives A systematic review of the literature was conducted to evaluate hypotensive agents in terms of their adverse effects and associations with perioperative morbidity in patients undergoing nasal surgery. Methods Two authors independently searched databases (Medline, Scopus, and Cochrane databases) up to February 2020 for randomized controlled trials comparing the perioperative administration of a hypotensive agent with a placebo or other agent. The outcomes of interest for this analysis were intraoperative morbidity, operative time, intraoperative bleeding, hypotension, postoperative nausea/vomiting, and postoperative pain. Both a standard pairwise meta-analysis and network meta-analysis were conducted. Results Our analysis was based on 37 trials. Treatment networks consisting of six interventions (placebo, clonidine, dexmedetomidine, beta-blockers, opioids, and nitroglycerine) were defined for the network meta-analysis. Dexmedetomidine resulted in the greatest differences in intraoperative bleeding (−0.971; 95% confidence interval [CI], −1.161 to −0.781), intraoperative fentanyl administration (−3.683; 95% CI, −4.848 to −2.518), and postoperative pain (−2.065; 95% CI, −3.170 to −0.960) compared with placebo. The greatest difference in operative time compared with placebo was achieved with clonidine (−0.699; 95% CI, −0.977 to −0.421). All other agents also had beneficial effects on the measured outcomes. Dexmedetomidine was less likely than other agents to cause adverse effects. Conclusion This study demonstrated the superiority of the systemic use of dexmedetomidine as a perioperative hypotensive agent compared with the other five tested agents. However, the other agents were also superior to placebo in improving operative time, intraoperative bleeding, and postoperative pain.
Background Selection Does Not Mimic the Patterns of Genetic Diversity Produced by Selective Sweeps

It is increasingly evident that natural selection plays a prominent role in shaping patterns of diversity across the genome. The most commonly studied modes of natural selection are positive selection and negative selection, which refer to directional selection for and against derived mutations, respectively. Positive selection can result in hitchhiking events, in which a beneficial allele rapidly replaces all others in the population, creating a valley of diversity around the selected site along with characteristic skews in allele frequencies and linkage disequilibrium among linked neutral polymorphisms. Similarly, negative selection reduces variation not only at selected sites but also at linked sites, a phenomenon called background selection (BGS). Thus, discriminating between these two forces may be difficult, and one might expect efforts to detect hitchhiking to produce an excess of false positives in regions affected by BGS. Here, we examine the similarity between BGS and hitchhiking models via simulation. First, we show that BGS may somewhat resemble hitchhiking in simplistic scenarios in which a region constrained by negative selection is flanked by large stretches of unconstrained sites, echoing previous results. However, this scenario does not mirror the actual spatial arrangement of selected sites across the genome. By performing forward simulations under more realistic scenarios of BGS, modeling the locations of protein-coding and conserved noncoding DNA in real genomes, we show that the spatial patterns of variation produced by BGS rarely mimic those of hitchhiking events. Indeed, BGS is not substantially more likely than neutrality to produce false signatures of hitchhiking. This holds for simulations modeled after both humans and Drosophila, and for several different demographic histories. These results demonstrate that appropriately designed scans for hitchhiking need not consider BGS’s impact on false-positive rates. However, we do find evidence that BGS increases the false-negative rate for hitchhiking, an observation that demands further investigation.