complex molecular networks and their regulation: Implications of strain heterogeneity on epigenetic diversity and transcriptome regulation.

Tuberculosis has been a public health crisis since the 1900, which has caused the highest mortalities due to a single bacterial infection worldwide, that was recently further complicated by the Coronavirus disease 2019 pandemic. The causative agent of Tuberculosis, , belongs to a genetically well-characterized family of strains known as the complex, which has complicated progress made towards eradicating Tuberculosis due to pathogen-specific phenotypic differences in the members of this complex. complex strains are genetically diverse human- and animal-adapted pathogens belonging to 7 lineages (Indo-Oceanic, East-Asian, East-African Indian, Euro-American, West Africa 1, West Africa 2 and Ethopia), respectively and the recently identified Lineage 8 and Lineage 9.

Neoantigen-targeted CD8 T cell responses with PD-1 blockade therapy.

Neoantigens are peptides derived from non-synonymous mutations presented by human leukocyte antigens (HLAs), which are recognized by antitumour T cells. The large HLA allele diversity and limiting clinical samples have restricted the study of the landscape of neoantigen-targeted T cell responses in patients over their treatment course. Here we applied recently developed technologies to capture neoantigen-specific T cells from blood and tumours from patients with metastatic melanoma with or without response to anti-programmed death receptor 1 (PD-1) immunotherapy.

Intravesical Instillation of OnabotulinumtoxinA in the Treatment of Refractory Overactive Bladder in Participants with Urinary Incontinence.

Purpose: Intradetrusor injections of onabotulinumtoxinA are efficacious for the treatment of overactive bladder with urgency urinary incontinence in adults refractory to or intolerant of anticholinergics. Delivery of onabotulinumtoxinA via instillation would reduce the need for intradetrusor injections. The objective of this trial was to assess the efficacy and safety of intravesical instillation of an onabotulinumtoxinA + hydrogel admixture.

Vaccination and vacci-notions: Understanding the barriers and facilitators of COVID-19 vaccine uptake during the 2020-21 COVID-19 pandemic.

Objective: The COVID-19 pandemic continues to place an inordinate burden on U.S. population health, and vaccination is the most powerful tool for curbing SARS-CoV-2 transmission, saving lives, and promoting economic recovery.

Pediatric Research Observing Trends and Exposures in COVID-19 Timelines (PROTECT): Protocol for a Multisite Longitudinal Cohort Study.

Background: Assessing the real-world effectiveness of COVID-19 vaccines and understanding the incidence and severity of SARS-CoV-2 illness in children are essential to inform policy and guide health care professionals in advising parents and caregivers of children who test positive for SARS-CoV-2.

Objective: This report describes the objectives and methods for conducting the Pediatric Research Observing Trends and Exposures in COVID-19 Timelines (PROTECT) study. PROTECT is a longitudinal prospective pediatric cohort study designed to estimate SARS-CoV-2 incidence and COVID-19 vaccine effectiveness (VE) against infection among children aged 6 months to 17 years, as well as differences in SARS-CoV-2 infection and vaccine response between children and adolescents.

Categorizing metadata to help mobilize computable biomedical knowledge.

Introduction: Computable biomedical knowledge artifacts (CBKs) are digital objects conveying biomedical knowledge in machine-interpretable structures. As more CBKs are produced and their complexity increases, the value obtained from sharing CBKs grows. Mobilizing CBKs and sharing them widely can only be achieved if the CBKs are findable, accessible, interoperable, reusable, and trustable (FAIR+T).

Crystal structures of a series of bis-(acetyl-aceto-nato)oxovanadium(IV) complexes containing N-donor pyridyl ligands.

Crystal structures for a series of bis-(acetyl-acetonato)oxovanadium(IV) complexes containing -donor pyridyl ligands are reported, namely, bis-(acetyl-acetonato-κ ,')oxido(pyridine-κ)vanadium(IV), [V(CHO)O(CHN)], , bis-(acetyl-acetonato-κ ,')oxido(pyridine-4-carbo-nitrile-κ)vanadium(IV), [V(CHO)O(CHN)], , and bis-(acetyl-acetonato-κ ,')(4-meth-oxy-pyridine-κ)oxidovanadium(IV), [V(CHO)O(CHNO)], , Compounds - have the formulae VO(CHO) , where = pyridine (), 4-cyano-pyridine (), and 4-meth-oxy-pyridine (). Compound was previously reported [Meicheng (1984 ▸). , , 759-764 and DaSilva, Spiazzi, Bortolotto & Burrow (2007).

Characteristics and outcomes of critically ill patients with severe hyperammonemia.

Purpose: To determine the etiology and outcomes of critically ill patients with severe hyperammonemia.

Materials And Methods: Retrospective observational study of adults (18 years or older) admitted to a MICU from 2007 to 2016 who had a serum ammonia level >180 μmol/L (3 times the upper limit of normal).

Results: The 78 patients (45 male, 32 female) had a median age of 52 (interquartile range [IQR] 46-58) years.

In Vivo Outcome of Homology-Directed Repair at the HBB Gene in HSC Using Alternative Donor Template Delivery Methods.

Gene editing following designer nuclease cleavage in the presence of a DNA donor template can revert mutations in disease-causing genes. For optimal benefit, reversion of the point mutation in HBB leading to sickle cell disease (SCD) would permit precise homology-directed repair (HDR) while concurrently limiting on-target non-homologous end joining (NHEJ)-based HBB disruption. In this study, we directly compared the relative efficiency of co-delivery of a novel CRISPR/Cas9 ribonucleoprotein targeting HBB in association with recombinant adeno-associated virus 6 (rAAV6) versus single-stranded oligodeoxynucleotides (ssODNs) to introduce the sickle mutation (GTC or GTG; encoding E6V) or a silent change (GAA; encoding E6optE) in human CD34 mobilized peripheral blood stem cells (mPBSCs) derived from healthy donors.

Appropriateness of Cardiac Troponin Testing: Insights from the Use of TROPonin In Acute coronary syndromes (UTROPIA) Study.

Objective: Our objective was to examine the appropriateness of cardiac troponin (cTn) testing among patients with cTn increases.

Methods: This is a planned secondary analysis of the Use of TROPonin In Acute coronary syndromes (UTROPIA, NCT02060760) observational cohort study. Appropriateness of cTn testing was adjudicated for emergency department patients with cTn increases >99 percentile and analyzed using both contemporary and high-sensitivity (hs) cTnI assays according to sub-specialty, diagnoses, and symptoms.

Three-month primary efficacy data for the SUCCESS Trial; a phase III, multi-center, prospective, randomized, controlled study treating female stress urinary incontinence with the vesair intravesical balloon.

Aims: The SUCCESS trial is a phase III study of the Vesair® balloon in the United States for female stress urinary incontinence (SUI). The purpose of this manuscript is to present the 3 month primary efficacy and tolerability outcome data.

Methods: The SUCCESS trial is a multi-center, prospective, single blind, randomized, sham-controlled study.

Twelve-Month Efficacy and Safety Data for the "Stress Incontinence Control, Efficacy and Safety Study": A Phase III, Multicenter, Prospective, Randomized, Controlled Study Treating Female Stress Urinary Incontinence Using the Vesair Intravesical Balloon.

Objectives: The "Stress Incontinence Control, Efficacy and Safety Study" (SUCCESS) is a phase III study of the Vesair Balloon in women with stress urinary incontinence who had failed conservative therapy, and either failed surgery, were not candidates for surgery, or chose not to have surgery. The safety and efficacy of the balloon at 12 months is reported for those participants in the treatment arm who elected to continue with the SUCCESS trial beyond the primary end point at 3 months.

Methods: The SUCCESS trial is a multicenter, prospective, single-blinded, randomized, sham-controlled study.

Type 1 and 2 Myocardial Infarction and Myocardial Injury: Clinical Transition to High-Sensitivity Cardiac Troponin I.

Background: Studies addressing patients with type 2 myocardial infarction and myocardial injury, including the impact of using high-sensitivity (hs) cardiac troponin (cTn) assays on their incidence are needed.

Methods: Ours is a prospective, observational US cohort study. Consecutive emergency department patients with serial cTnI measurements were studied.

Diagnostic Performance of High Sensitivity Compared with Contemporary Cardiac Troponin I for the Diagnosis of Acute Myocardial Infarction.

Background: We examined the diagnostic performance of high-sensitivity cardiac troponin I (hs-cTnI) vs contemporary cTnI with use of the 99th percentile alone and with a normal electrocardiogram (ECG) to rule out acute myocardial infarction (MI) and serial changes (deltas) to rule in MI.

Methods: We included consecutive patients presenting to a US emergency department with serial cTnI onclinical indication. Diagnostic performance for acute MI, including MI subtypes, and 30-day outcomes were examined.

Measuring and predicting the diffraction properties of cylindrically bent potassium acid phthalate, KAP(001), crystals.

This report presents the results from measuring the X-ray diffraction properties of a curved potassium acid phthalate (KAP(001)) spectrometer crystal using two measurement methods. One method used a diode type X-ray source and a dual goniometer analysis system, utilizing a flat, perfect KAP(001) crystal as the monochromator. The second method used a synchrotron source and dual crystal Si(111) monochromator.

Characterization of homing endonuclease binding and cleavage specificities using yeast surface display SELEX (YSD-SELEX).

LAGLIDADG homing endonucleases (LHEs) are a class of rare-cleaving nucleases that possess several unique attributes for genome engineering applications. An important approach for advancing LHE technology is the generation of a library of design ‘starting points’ through the discovery and characterization of natural LHEs with diverse specificities. However, while identification of natural LHE proteins by sequence homology from genomic and metagenomic sequence databases is straightforward, prediction of corresponding target sequences from genomic data remains challenging.

A technique for measuring the quality of an elliptically bent pentaerythritol [PET(002)] crystal.

We present a technique for determining the X-ray spectral quality from each region of an elliptically curved PET(002) crystal. The investigative technique utilizes the shape of the crystal rocking curve which changes significantly as the radius of curvature changes. This unique quality information enables the spectroscopist to verify where in the spectral range that the spectrometer performance is satisfactory and where there are regions that would show spectral distortion.

Discordance between ICD-Coded Myocardial Infarction and Diagnosis according to the Universal Definition of Myocardial Infarction.

Background: International Classification of Diseases (ICD) coding is the standard diagnostic tool for healthcare management. At present, type 2 myocardial infarction (T2MI) classification by the Universal Definition of Myocardial Infarction (MI) remains ignored in the ICD system. We determined the concordance for the diagnosis of MI using ICD-9 coding vs the Universal Definition.

Measuring the diffraction properties of an imaging quartz(211) crystal.

A dual goniometer X-ray system was used to measure the reflectivity curve for a spherically bent quartz(211) crystal. An analysis of the dual goniometer instrument response function for the rocking curve width measurement was developed and tested against the actual measurements. The rocking curve was measured at 4510.

High Efficiency CRISPR/Cas9-mediated Gene Editing in Primary Human T-cells Using Mutant Adenoviral E4orf6/E1b55k "Helper" Proteins.

Many future therapeutic applications of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 and related RNA-guided nucleases are likely to require their use to promote gene targeting, thus necessitating development of methods that provide for delivery of three components-Cas9, guide RNAs and recombination templates-to primary cells rendered proficient for homology-directed repair. Here, we demonstrate an electroporation/transduction codelivery method that utilizes mRNA to express both Cas9 and mutant adenoviral E4orf6 and E1b55k helper proteins in association with adeno-associated virus (AAV) vectors expressing guide RNAs and recombination templates. By transiently enhancing target cell permissiveness to AAV transduction and gene editing efficiency, this novel approach promotes efficient gene disruption and/or gene targeting at multiple loci in primary human T-cells, illustrating its broad potential for application in translational gene editing.

pEVL: A Linear Plasmid for Generating mRNA IVT Templates With Extended Encoded Poly(A) Sequences.

Increasing demand for large-scale synthesis of in vitro transcribed (IVT) mRNA is being driven by the increasing use of mRNA for transient gene expression in cell engineering and therapeutic applications. An important determinant of IVT mRNA potency is the 3' polyadenosine (poly(A)) tail, the length of which correlates with translational efficiency. However, present methods for generation of IVT mRNA rely on templates derived from circular plasmids or PCR products, in which homopolymeric tracts are unstable, thus limiting encoded poly(A) tail lengths to ~120 base pairs (bp).