A patient with COVID-19-related severe respiratory failure, with insufficient response to an antiretroviral therapy, hydroxychloroquine and Interleukin-6 (IL-6) antagonist therapy, presented a prompt ...resolution of the respiratory function and improvement in the radiological picture after baricitinib at an oral dose of 4 mg per day for 2 weeks.
To develop a deep learning-based decision tree for the primary care setting, to stratify adult patients with confirmed and unconfirmed coronavirus disease 2019 (COVID-19), and to predict the need for ...hospitalization or home monitoring.
We performed a retrospective cohort study on data from patients admitted to a COVID hospital in Rome, Italy, between 5 March 2020 and 5 June 2020. A confirmed case was defined as a patient with a positive nasopharyngeal RT-PCR test result, while an unconfirmed case had negative results on repeated swabs. Patients' medical history and clinical, laboratory and radiological findings were collected, and the dataset was used to train a predictive model for COVID-19 severity.
Data of 198 patients were included in the study. Twenty-eight (14.14%) had mild disease, 62 (31.31%) had moderate disease, 64 (32.32%) had severe disease, and 44 (22.22%) had critical disease. The G2 value assessed the contribution of each collected value to decision tree building. On this basis, SpO2 (%) with a cut point at 92 was chosen for the optimal first split. Therefore, the decision tree was built using values maximizing G2 and LogWorth. After the tree was built, the correspondence between inputs and outcomes was validated.
We developed a machine learning-based tool that is easy to understand and apply. It provides good discrimination in stratifying confirmed and unconfirmed COVID-19 patients with different prognoses in every context. Our tool might allow general practitioners visiting patients at home to decide whether the patient needs to be hospitalized.
Insulin resistance in skeletal muscle is a major risk factor for the development of type 2 diabetes in women with polycystic ovary syndrome (PCOS). Despite this, the mechanisms underlying insulin ...resistance in PCOS are largely unknown.
To investigate the genome-wide DNA methylation and gene expression patterns in skeletal muscle from women with PCOS and controls and relate them to phenotypic variations.
In a case-control study, skeletal muscle biopsies from women with PCOS (n = 17) and age-, weight-, and body mass index‒matched controls (n = 14) were analyzed by array-based DNA methylation and mRNA expression profiling.
Eighty-five unique transcripts were differentially expressed in muscle from women with PCOS vs controls, including DYRK1A, SYNPO2, SCP2, and NAMPT. Furthermore, women with PCOS had reduced expression of genes involved in immune system pathways. Two CpG sites showed differential DNA methylation after correction for multiple testing. However, an mRNA expression of ∼30% of the differentially expressed genes correlated with DNA methylation levels of CpG sites in or near the gene. Functional follow-up studies demonstrated that KLF10 is under transcriptional control of insulin, where insulin promotes glycogen accumulation in myotubes of human muscle cells. Testosterone downregulates the expression levels of COL1A1 and MAP2K6.
PCOS is associated with aberrant skeletal muscle gene expression with dysregulated pathways. Furthermore, we identified specific changes in muscle DNA methylation that may affect gene expression. This study showed that women with PCOS have epigenetic and transcriptional changes in skeletal muscle that, in part, can explain the metabolic abnormalities seen in these women.
Frailty has been shown to be associated with poor perioperative outcomes including increased mortality, morbidity, and hospital length of stay. Fig. 1 illustrates a normal rectus femoris CSA of ...5.67cm2 in a fit 68-year-old patient (with a body surface area of 1.73m2), whilst Fig. 2 illustrates a significantly reduced rectus femoris CSA of 2.08cm2 in a frail 70-year-old patient (with a body surface area of 1.74m2) with a 6-min walk test result of only 150 m. In the frail patient, the rectus femoris appears flattened (reduced thickness) with increased echogenicity indicative of fat infiltration. The use of rectus femoris ultrasonography can therefore be used as a convenient means of monitoring progress and guiding prehabilitation strategies with the ultimate aim of improving perioperative outcomes.Declaration of Competing Interest Author has no conflict of interest and no external funding to disclose.
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•Curcumin-2-HP-β-CD complex enhanced solubility in physiological medium.•Chitosan microspheres encapsulating soluble curcumin improved drug delivery.•Chitosan microspheres ...encapsulating soluble curcumin augmented therapeutic index.
In present investigation, initially curcumin was complexed with 2-HP-β-CD (curcumin-2-HP-β-CD-complex) in 1:1 ratio and later amalgamated with chitosan microspheres (curcumin-2-HP-β-CD-CMs) for selective delivery in colon only through oral route of administration. Various analytical, spectral and in-silico docking techniques revealed that the curcumin was deeply inserted in the 2-HP-β-CD cavity with apparent stability constant of 3.35×10−3M. Furthermore, the mean particle size of 6.8±2.6μm and +39.2±4.1mV surface charge of curcumin-2-HP-β-CD-complex-CMs in addition to encapsulation efficiency of about 79.8±6.3% exhibited that the tailored microspheres were optimum for colon delivery of curcumin. This was also demonstrated in dissolution testing and standard cell proliferation assay in which curcumin-2-HP-β-CD-complex-CMs exhibited maximum release in simulated colonic fluid (SCF, pH ∼7.0–8.0, almond emulsion-β-glucosidase) with improved therapeutic index in HT-29 cells. Consistently, curcumin-2-HP-β-CD-complex-CMs successively enhanced the colonic bio-distribution of curcumin by ∼8.36 folds as compared to curcumin suspension in preclinical pharmacokinetic studies. In conclusion, curcumin-2-HP-β-CD-complex-CMs warrant further in vivo tumor regression study to establish its therapeutic efficacy in experimental colon cancer.
Summary
We report on a whole‐genome draft sequence of rye (Secale cereale L.). Rye is a diploid Triticeae species closely related to wheat and barley, and an important crop for food and feed in ...Central and Eastern Europe. Through whole‐genome shotgun sequencing of the 7.9‐Gbp genome of the winter rye inbred line Lo7 we obtained a de novo assembly represented by 1.29 million scaffolds covering a total length of 2.8 Gbp. Our reference sequence represents nearly the entire low‐copy portion of the rye genome. This genome assembly was used to predict 27 784 rye gene models based on homology to sequenced grass genomes. Through resequencing of 10 rye inbred lines and one accession of the wild relative S. vavilovii, we discovered more than 90 million single nucleotide variants and short insertions/deletions in the rye genome. From these variants, we developed the high‐density Rye600k genotyping array with 600 843 markers, which enabled anchoring the sequence contigs along a high‐density genetic map and establishing a synteny‐based virtual gene order. Genotyping data were used to characterize the diversity of rye breeding pools and genetic resources, and to obtain a genome‐wide map of selection signals differentiating the divergent gene pools. This rye whole‐genome sequence closes a gap in Triticeae genome research, and will be highly valuable for comparative genomics, functional studies and genome‐based breeding in rye.
Significance statement
Rye is a diploid Triticeae species closely related to wheat and barley. Here we present a draft genome and a high‐density genotyping array that will facilitate genome‐based research in rye and comparative genomics in Triticeae.
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