Explore the vast range of titles available.

The factors that control the growth and infectious processes for Chlamydia are still poorly understood. This study used recently developed genetic tools to determine the regulon for one of the key transcription factors encoded by Chlamydia , sigma 54. Surrogate and computational analyses provide additional support for the hypothesis that sigma 54 plays a key role in controlling the expression of many components critical to converting and enabling the infectious capability of Chlamydia . These components include those that remodel the membrane for the extracellular environment and incorporation of an arsenal of type III secretion effectors in preparation for infecting new cells. Chlamydia bacteria are obligate intracellular organisms with a phylum-defining biphasic developmental cycle that is intrinsically linked to its ability to cause disease. The progression of the chlamydial developmental cycle is regulated by the temporal expression of genes predominantly controlled by RNA polymerase sigma (σ) factors. Sigma 54 (σ 54 ) is one of three sigma factors encoded by Chlamydia for which the role and regulon are unknown. CtcC is part of a two-component signal transduction system that is requisite for σ 54 transcriptional activation. CtcC activation of σ 54 requires phosphorylation, which relieves inhibition by the CtcC regulatory domain and enables ATP hydrolysis by the ATPase domain. Prior studies with CtcC homologs in other organisms have shown that expression of the ATPase domain alone can activate σ 54 transcription. Biochemical analysis of CtcC ATPase domain supported the idea of ATP hydrolysis occurring in the absence of the regulatory domain, as well as the presence of an active-site residue essential for ATPase activity (E242). Using recently developed genetic approaches in Chlamydia to induce expression of the CtcC ATPase domain, a transcriptional profile was determined that is expected to reflect the σ 54 regulon. Computational evaluation revealed that the majority of the differentially expressed genes were preceded by highly conserved σ 54 promoter elements. Reporter gene analyses using these putative σ 54 promoters reinforced the accuracy of the model of the proposed regulon. Investigation of the gene products included in this regulon supports the idea that σ 54 controls expression of genes that are critical for conversion of Chlamydia from replicative reticulate bodies into infectious elementary bodies. IMPORTANCE The factors that control the growth and infectious processes for Chlamydia are still poorly understood. This study used recently developed genetic tools to determine the regulon for one of the key transcription factors encoded by Chlamydia , sigma 54. Surrogate and computational analyses provide additional support for the hypothesis that sigma 54 plays a key role in controlling the expression of many components critical to converting and enabling the infectious capability of Chlamydia . These components include those that remodel the membrane for the extracellular environment and incorporation of an arsenal of type III secretion effectors in preparation for infecting new cells.

ObjectiveTo compare radioembolization treatment zone volumes from mapping cone beam CT (CBCT) versus planning CT/MRI and to model their impact on dosimetry.MethodsY90 cases were retrospectively identified in which intra-procedural CBCT angiograms were performed. Segmental and lobar treatment zone volumes were calculated with semi-automated contouring using Couinaud venous anatomy (planning CT/MRI) or tumor angiosome enhancement (CBCT). Differences were compared with a Wilcoxon signed-rank test. Treatment zone-specific differences in segmental volumes by volumetric method were also calculated and used to model differences in delivered dose using medical internal radiation dosimetry (MIRD) at 200 and 120 Gy targets. Anatomic, pathologic, and technical factors likely affecting segmental volumes by volumetric method were evaluated.ResultsForty segmental and 48 lobar CBCT angiograms and corresponding planning CT/MRI scans were included. Median Couinaud- and CBCT-derived segmental volumes were 281 and 243 mL, respectively (p = 0.005). Differences between Couinaud and CBCT lobar volumes (right, left) were not significant (p = 0.24, p = 0.07). Couinaud overestimated segmental volumes in 28 cases by a median of 98 mL (83%) and underestimated in 12 cases by median 69 mL (20%). At a 200 Gy dose target, Couinaud estimates produced median delivered doses of 367 and 160 Gy in these 28 and 12 cases. At a 120 Gy target, Couinaud produced doses of 220 and 96 Gy. Proximal vs. distal microcatheter positioning, variant arterial anatomy, and tumor location on or near segmental watersheds were leading factors linked to volumetric differences.ConclusionUse of CBCT-based volumetry may allow more accurate, personalized dosimetry for segmental Y90 radioembolization.

Background Nonalcoholic Fatty Liver Disease (NAFLD) is a common co-morbidity of obesity. Elevated TSH levels (eTSH), also associated with obesity, may contribute to the dysmetabolic state that predisposes to NAFLD. Objective To assess the relationship between TSH levels and NAFLD in children with biopsy-proven NAFLD compared to controls. Design and methods In this retrospective study of children with biopsy-proven NAFLD and age-matched controls, the association of eTSH with NAFLD was investigated and the role of TSH as a mediator between obesity and NAFLD was assessed. Results Sixty-six cases and 4067 controls (69.7 vs 59% Hispanic/Latino ancestry, p = 0.1) of the same age range seen in the same time duration at an urban Children's Hospital were studied. Children with NAFLD were more likely to be male (74.6 vs 39.4%, p < 0.001), have higher modified BMI-z scores (median 2.4 (IQR 1.7) vs 1.9 (IQR 1.7), p < 0.001), and abnormal metabolic parameters (TSH, ALT, HDL-C, non-HDL-C, and TG). Multivariate analyses controlling for age, sex and severity of obesity showed significant association between the 4.sup.th quartile of TSH and NAFLD. Causal mediation analysis demonstrates that TSH mediates 33.8% of the effect of modified BMI-z score on NAFLD. This comprises of 16.0% (OR = 1.1, p = 0.002) caused by the indirect effect of TSH and its interaction with modified BMI-z, and 17.7% (OR = 1.1, p = 0.05) as an autonomous effect of TSH on NAFLD. Overall, 33.8% of the effect can be eliminated by removing the mediator, TSH (p = 0.001). Conclusions The association of eTSH and biopsy-proven NAFLD is demonstrated in children of Hispanic/Latino ancestry. Further, a causal mediation analysis implicates an effect of TSH on NAFLD, independent of obesity.

Candidemia caused by Candida spp. is a serious threat in hospital settings being a major cause of acquired infection and death and a possible contributor to Covid-19 mortality. Candidemia incidence has been rising worldwide following increases in fungicide-resistant pathogens highlighting the need for more effective antifungal agents with novel modes of action. The membrane-bound enzyme alternative oxidase (AOX) promotes fungicide resistance and is absent in humans making it a desirable therapeutic target. However, the lipophilic nature of the AOX substrate (ubiquinol-10) has hindered its kinetic characterisation in physiologically-relevant conditions. Here, we present the purification and expression of recombinant AOXs from C. albicans and C. auris in a self-assembled proteoliposome (PL) system. Kinetic parameters (K m and V max ) with respect to ubiquinol-10 have been determined. The PL system has also been employed in dose–response assays with novel AOX inhibitors. Such information is critical for the future development of novel treatments for Candidemia.

Background Racial and ethnic minority groups experience a disproportionate burden of SARS‐CoV‐2 illness and studies suggest that cancer patients are at a particular risk for severe SARS‐CoV‐2 infection. Aims The objective of this study was examine the association between neighborhood characteristics and SARS‐CoV‐2 infection among patients with cancer. Methods and Results We performed a cross‐sectional study of New York City residents receiving treatment for cancer at a tertiary cancer center. Patients were linked by their address to data from the US Census Bureau's American Community Survey and to real estate tax data from New York's Department of City Planning. Models were used to both to estimate odds ratios (ORs) per unit increase and to predict probabilities (and 95% CI) of SARS‐CoV2 infection. We identified 2350 New York City residents with cancer receiving treatment. Overall, 214 (9.1%) were infected with SARS‐CoV‐2. In adjusted models, the percentage of Hispanic/Latino population (aOR = 1.01; 95% CI, 1.005–1.02), unemployment rate (aOR = 1.10; 95% CI, 1.05–1.16), poverty rates (aOR = 1.02; 95% CI, 1.0002–1.03), rate of >1 person per room (aOR = 1.04; 95% CI, 1.01–1.07), average household size (aOR = 1.79; 95% CI, 1.23–2.59) and population density (aOR = 1.86; 95% CI, 1.27–2.72) were associated with SARS‐CoV‐2 infection. Conclusion Among cancer patients in New York City receiving anti‐cancer therapy, SARS‐CoV‐2 infection was associated with neighborhood‐ and building‐level markers of larger household membership, household crowding, and low socioeconomic status. Novelty and impact We performed a cross‐sectional analysis of residents of New York City receiving treatment for cancer in which we linked subjects to census and real estate date. This linkage is a novel way to examine the neighborhood characteristics that influence SARS‐COV‐2 infection. We found that among patients receiving anti‐cancer therapy, SARS‐CoV‐2 infection was associated with building and neighborhood‐level markers of household crowding, larger household membership, and low socioeconomic status. With ongoing surges of SARS‐CoV‐2 infections, these data may help in the development of interventions to decrease the morbidity and mortality associated with SARS‐CoV‐2 among cancer patients.

We present the outcomes of a program designed to engage primary school students with both Indigenous knowledge and biodiversity conservation, through the lens of “Totemic” species. The program provided resources for genuine engagement with Traditional Owners, and for the coordinating teachers to dedicate time to curriculum development and delivery. The material was embedded within a cross‐school core curriculum topic (biology), presenting both Indigenous and Western knowledge in parallel. Students' understanding of ecology and conservation increased significantly post‐program, as did their cultural awareness and appreciation of traditional knowledge. Care for the totemic species was also shown to increase and enthusiasm for this approach to teaching science was expressed by students. The co‐benefits of this program include creating habitat for threatened species, improvements in the health and wellbeing of students through engagement with biodiversity and the potential for ecosystem services such as cooling of the school grounds. Effective ways of embedding cultural awareness and Indigenous knowledge into the Australian curriculum are urgently needed and it is our hope that this program provides evidence of effective ways of embedding these knowledges moving forward. We present the outcomes of a program designed to engage primary school students with both Indigenous knowledge and biodiversity conservation, through the lens of “Totemic” species. The program provided resources for genuine engagement with Traditional Owners, and for the coordinating teachers to dedicate time to curriculum development and delivery. The material was embedded within a cross‐school core curriculum topic (biology), presenting both Indigenous and Western knowledge in parallel.

Interference by foreign actors in democratic elections has occurred since the founding of the United States, but it has become a topic of intense importance in the first quarter of the 21st century. The Russian government in particular has interfered in multiple foreign democratic elections since the early 2000s. Influencing elections particularly through information manipulation online and on social media has become their favorite form of election interference. In 2016, the Russian government interfered in the United States presidential election through online disinformation campaigns. Researchers conclude that they sought to sway voters to vote for then-candidate Donald Trump and to disparage Hillary Clinton and her candidacy. This had a significant effect on the American democratic process, potentially influencing its outcome. The process of what happened, how it happened, and who was responsible has been explored by multiple scholars. However, understanding and investigating why it happened is currently lacking in academic work. This thesis will seek to contribute to this important yet sparse field of knowledge and attempt to answer why the Russians interfered in the 2016 election. The concept used to explore this question is hybrid war theory.

PurposeDeep learning techniques, including convolutional neural networks (CNN), have the potential to improve breast cancer risk prediction compared to traditional risk models. We assessed whether combining a CNN-based mammographic evaluation with clinical factors in the Breast Cancer Surveillance Consortium (BCSC) model improved risk prediction.MethodsWe conducted a retrospective cohort study among 23,467 women, age 35–74, undergoing screening mammography (2014–2018). We extracted electronic health record (EHR) data on risk factors. We identified 121 women who subsequently developed invasive breast cancer at least 1 year after the baseline mammogram. Mammograms were analyzed with a pixel-wise mammographic evaluation using CNN architecture. We used logistic regression models with breast cancer incidence as the outcome and predictors including clinical factors only (BCSC model) or combined with CNN risk score (hybrid model). We compared model prediction performance via area under the receiver operating characteristics curves (AUCs).ResultsMean age was 55.9 years (SD, 9.5) with 9.3% non-Hispanic Black and 36% Hispanic. Our hybrid model did not significantly improve risk prediction compared to the BCSC model (AUC of 0.654 vs 0.624, respectively, p = 0.063). In subgroup analyses, the hybrid model outperformed the BCSC model among non-Hispanic Blacks (AUC 0.845 vs. 0.589; p = 0.026) and Hispanics (AUC 0.650 vs 0.595; p = 0.049).ConclusionWe aimed to develop an efficient breast cancer risk assessment method using CNN risk score and clinical factors from the EHR. With future validation in a larger cohort, our CNN model combined with clinical factors may help predict breast cancer risk in a cohort of racially/ethnically diverse women undergoing screening.

BackgroundGastrointestinal symptoms are common in patients with COVID-19, but prevalence of co-infection with enteric pathogens is unknown.AimsThis study assessed the prevalence of enteric infections among hospitalized patients with COVID-19.MethodsWe evaluated 4973 hospitalized patients ≥ 18 years of age tested for COVID-19 from March 11 through April 28, 2020, at two academic hospitals. The primary exposure was a positive COVID-19 test. The primary outcome was detection of a gastrointestinal pathogen by PCR stool testing.ResultsAmong 4973 hospitalized individuals, 311 were tested for gastrointestinal infections (204 COVID-19 positive, 107 COVID-19 negative). Patients with COVID-19 were less likely to test positive compared to patients without COVID-19 (10% vs 22%, p < 0.01). This trend was driven by lower rates of non-C.difficile infections (11% vs 22% in COVID-19 positive vs. negative, respectively, p = 0.04), but not C. difficile infection (5.1% vs. 8.2%, p = 0.33). On multivariable analysis, infection with COVID-19 remained significantly associated with lower odds of concurrent GI infection (aOR 0.49, 95% CI 0.24–0.97), again driven by reduced non-C.difficile infection. Testing for both C.difficile and non-C.difficile enteric infection decreased dramatically during the pandemic.ConclusionsPathogens aside from C.difficile do not appear to be a significant contributor to diarrhea in COVID-19 positive patients.