Pridgenaagaard8039

Posttraining survey results revealed that LSA was not performed more often in daily practice. Using CLAN was not the solution according to participating SLPs. Time investment remained a huge barrier. Conclusions A training in performing LSA did not resolve the time investment barrier experienced by SLPs. User-friendly software, developed in codesign with SLPs might provide a solution. For the short-term, shorter samples, preferably from narrative tasks, should be considered.

Typically stored as unstructured notes, surgical pathology reports contain data elements valuable to cancer research that require labor-intensive manual extraction. Although studies have described natural language processing (NLP) of surgical pathology reports to automate information extraction, efforts have focused on specific cancer subtypes rather than across multiple oncologic domains. To address this gap, we developed and evaluated an NLP method to extract tumor staging and diagnosis information across multiple cancer subtypes.

The NLP pipeline was implemented on an open-source framework called Leo. We used a total of 555,681 surgical pathology reports of 329,076 patients to develop the pipeline and evaluated our approach on subsets of reports from patients with breast, prostate, colorectal, and randomly selected cancer subtypes.

Averaged across all four cancer subtypes, the NLP pipeline achieved an accuracy of 1.00 for International Classification of Diseases, Tenth Revision codes, 0.89 for T stagNLP approach-and reusing code available at GitHub-to support the oncology research enterprise with elements extracted from surgical pathology reports.

Complex molecular programs in specific cell lineages govern human heart development. Hypoplastic left heart syndrome (HLHS) is the most common and severe manifestation within the spectrum of left ventricular outflow tract obstruction defects occurring in association with ventricular hypoplasia. The pathogenesis of HLHS is unknown, but hemodynamic disturbances are assumed to play a prominent role.

To identify perturbations in gene programs controlling ventricular muscle lineage development in HLHS, we performed whole-exome sequencing of 87 HLHS parent-offspring trios, nuclear transcriptomics of cardiomyocytes from ventricles of 4 patients with HLHS and 15 controls at different stages of heart development, single cell RNA sequencing, and 3D modeling in induced pluripotent stem cells from 3 patients with HLHS and 3 controls.

Gene set enrichment and protein network analyses of damaging de novo mutations and dysregulated genes from ventricles of patients with HLHS suggested alterations in specific gene progry in HLHS, many mutations converge on sequential cellular processes primarily driving cardiac myogenesis, suggesting novel therapeutic approaches.Heart disease remains one of the greatest killers. In addition to genetics and traditional lifestyle risk factors, we now understand that adverse conditions during pregnancy can also increase susceptibility to cardiovascular disease in the offspring. Therefore, the mechanisms by which this occurs and possible preventative therapies are of significant contemporary interest to the cardiovascular community. A common suboptimal pregnancy condition is a sustained reduction in fetal oxygenation. Chronic fetal hypoxia results from any pregnancy with increased placental vascular resistance, such as in preeclampsia, placental infection, or maternal obesity. Chronic fetal hypoxia may also arise during pregnancy at high altitude or because of maternal respiratory disease. This article reviews the short- and long-term effects of hypoxia on the fetal cardiovascular system, and the importance of chronic fetal hypoxia in triggering a developmental origin of future heart disease in the adult progeny. The work summarizes evidence derived from human studies as well as from rodent, avian, and ovine models. There is a focus on the discovery of the molecular link between prenatal hypoxia, oxidative stress, and increased cardiovascular risk in adult offspring. Discussion of mitochondria-targeted antioxidant therapy offers potential targets for clinical intervention in human pregnancy complicated by chronic fetal hypoxia.

The Pediatric Oncology COVID-19 Case Report registry supplies pediatric oncologists with data surrounding the clinical course and outcomes in children with cancer and SARS-CoV-2.

This observational study captured clinical and sociodemographic characteristics for children (≤ 21 years) receiving cancer therapy and infected with SARS-CoV-2 from the pandemic onset through February 19, 2021. The demographic and clinical characteristics of the cohort were compared with population-level pediatric oncology data (SEER). Multivariable binomial regression models evaluated patient characteristics associated with hospitalization, intensive care unit (ICU) admission, and changes in cancer therapy.

Ninety-four institutions contributed details on 917 children with cancer and SARS-CoV-2. Median age at SARS-CoV-2 infection was 11 years (range, 0-21 years). Compared with SEER, there was an over-representation of Hispanics (43.6%

29.7%,

< .01), publicly insured (59.3%

33.5%,

< .01), and patients with hemaational cohort suggests disparities that require attention.

These findings provide critical information for decision making among pediatric oncologists, including inpatient versus outpatient management, cancer therapy modifications, consideration of monoclonal antibody therapy, and counseling families on infection risks in the setting of the SARS-CoV-2 pandemic. The over-representation of Hispanic and publicly insured patients in this national cohort suggests disparities that require attention.In investigating the epidemiological trends of Salmonella enterica serovar Goldcoast, we have previously identified several closely related strains with different MICs to azithromycin and quinolones. Genome sequencing and comparison of two very similar MDR strains, R18.0877 and R18.1656, has led to the identification of an extra plasmid-borne ramA gene, ramAp, on the large IncHI2 plasmid carried by R18.0877. The ramAp is located in a 953-bp region on the plasmid, which is identical to that of the Klebsiella quasipneumoniae chromosomal ramA loci. A truncated ISEcp1 located at the adjacent upstream of the putative regulatory region of the ramAp may likely contribute to its mobilization and expression. Introducing the ramAp and the truncated ISEcp1 into E. coli have resulted in elevated expression of efflux pump genes and elevated MICs to chloramphenicol, azithromycin, nalidixic acid, ciprofloxacin, sulfamethoxazole, trimethoprim, tetracycline, and tigecycline. The ramAp is an extra efflux pump activator gene that potentially could be transmitted with the IncHI2 plasmid among bacteria. It is plausible that, with high interspecific conservation, the plasmid-encoded regulator reduces drug susceptibility by activating existing efflux pump systems of the host and thus can be regarded as a new type of auxiliary antimicrobial resistance determinant. Sequences of similar plasmids were found worldwide. Its impact on the emergence of antimicrobial resistance among bacterial pathogens is worrisome.Antibiotic tolerant Staphylococcus aureus pose a great challenge to clinicians as well as to microbiological laboratories and are one reason for treatment failure. Antibiotic tolerant strains survive transient antibiotic exposure despite being fully susceptible in vitro. Thus, fast and reliable methods to detect tolerance in the routine microbiology laboratory are urgently required. We therefore evaluated the feasibility of the replica plating tolerance isolation system (REPTIS) to detect antibiotic tolerance in S. aureus isolates derived directly from patients suffering from different types of infections and investigated possible connections to clinical presentations and patient characteristics. One hundred twenty-five S. aureus isolates were included. Replica plating of the original resistance testing plate was used to assess regrowth in the zones of inhibition, indicating antibiotic tolerance. Bacterial regrowth was assessed after 24 and 48 hours of incubation and an overall regrowth score (ORS) was assigned. Regrowth scores were compared to the clinical presentation. Bacterial regrowth was high for most antibiotics targeting protein synthesis and relatively low for antibiotics targeting other cellular functions such as DNA-replication, transcription and cell wall synthesis, with the exception of rifampicin. Isolates with a blaZ penicillinase had lower regrowth in penicillin and ampicillin. Low ORSs were more prevalent among isolates recovered from patients with immunosuppression or methicillin-resistant S. aureus (MRSA) isolates. In conclusion, REPTIS is useful to detect antibiotic tolerance in clinical microbiological routine diagnostics. Further studies should evaluate the impact of rapid detection of antibiotic tolerance as a clinical decision-making tool for tailored antibiotic treatments.The α-hydroxytropolones (αHT) are troponoid inhibitors of hepatitis B virus (HBV) replication that can target the HBV ribonuclease H (RNase H) with sub-micromolar efficacies. αHTs and related troponoids (tropones and tropolones) can be cytotoxic in cell lines as measured by MTS assays that assesses mitochondrial function. Earlier studies suggest that tropolones induce cytotoxicity through inhibition of mitochondrial respiration. ALK inhibitor Therefore, we screened 35 diverse troponoids for effects on mitochondrial function, mitochondrialnuclear genome ratio, cytotoxicity, and reactive oxygen species (ROS) production. Troponoids as a class did not inhibit respiration or glycolysis, although the α-ketotropolone subclass did interfere with these processes. The troponoids had no impact on the mitochondrial DNA to nuclear DNA ratio after three days of compound exposure. Patterns of troponoid-induced cytotoxicity among three hepatic cell lines were similar for all compounds, but three potent HBV RNase H inhibitors were not cytotoxic in primary human hepatocytes. Tropolones and αHTs increased ROS production in cells at cytotoxic concentrations but had no effect at lower concentrations that efficiently inhibit HBV replication. Troponoid-mediated cytotoxicity was significantly decreased upon addition of the ROS scavenger N-acetylcysteine. These studies show that troponoids can increase ROS production at high concentrations within cell lines leading to cytotoxicity, but are not be cytotoxic in primary hepatocytes. Future development of αHTs as potential therapeutics against HBV may need to mitigate ROS production by altering compound design and/or by co-administration with ROS antagonists to ameliorate increased ROS levels.Pseudomonas aeruginosa is a Gram-negative, opportunistic pathogen which is involved in numerous infections. It is of growing concern within the field of antibiotic resistant and tolerance and often exhibits multi-drug resistance. Previous studies have shown the emergence of antibiotic resistant and tolerant variants within the zone of clearance of a biofilm lawn after exposure to aminoglycosides. As concerning as the tolerant variant emergence is, there was also a zone of killing (ZOK) immediately surrounding the antibiotic source from which no detectable bacteria emerged or were cultured. In this study, the ZOK was analyzed using both in vitro and in silico methods to determine if there was a consistent antibiotic concentration versus time constraint (area under the curve, (AUC)) which is able to completely kill all bacteria in the lawn biofilms in our in vitro model. Our studies revealed that by achieving an average AUC of 4,372.5 μg*hr/mL, complete eradication of biofilms grown on both agar and hydroxyapatite was possible.