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Background The most accurate method for estimating effective dose (the most widely understood metric for tracking patient radiation exposure) from computed tomography (CT) requires time-intensive Monte Carlo simulation. A simpler method multiplies a scalar coefficient by the widely available scanner-reported dose length product (DLP) to estimate effective dose. Objective Develop pediatric effective dose coefficients and assess their agreement with Monte Carlo simulation. Materials and methods Multicenter, population-based sample of 128,397 pediatric diagnostic CT scans prospectively assembled in 2015–2020 from the University of California San Francisco International CT Dose Registry and the University of Florida library of highly realistic hybrid computational phantoms. We generated effective dose coefficients for seven body regions, stratified by patient age, diameter, and scanner manufacturer. We applied the new coefficients to DLPs to calculate effective doses and assessed their correlations with Monte Carlo radiation transport-generated effective doses. Results The reported effective dose coefficients, generally higher than previous studies, varied by body region and decreased in magnitude with increasing age. Coefficients were approximately 4 to 13-fold higher (across body regions) for patients Conclusions New pediatric effective dose coefficients update existing literature and can be used to easily estimate effective dose using scanner-reported DLP.

Background San Francisco implemented one of the earliest shelter-in-place public health mandates in the U.S., with flattened curves of diagnoses and deaths. We describe demographics, clinical features and outcomes of COVID-19 patients admitted to a public health hospital in a high population-density city with an early containment response. Methods We analyzed inpatients with COVID-19 admitted to San Francisco General Hospital (SFGH) from 3/5/2020–5/11/2020. SFGH serves a network of >63,000 patients (32% Latinx/24% Asian/19% African American/19% Caucasian). Demographic and clinical data through 5/18/2020 were abstracted from hospital records, along with ICU and ventilator utilization, lengths of stay, and in-hospital deaths. Results Of 157 admitted patients, 105/157 (67%) were male, median age was 49 (range 19-96y), and 127/157 (81%) of patients with COVID-19 were Latinx. Crowded living conditions were common: 60/157 (38%) lived in multi-family shared housing, 12/1578 (8%) with multigenerational families, and 8/157 (5%) were homeless living in shelters. Of 102 patients with ascertained occupations, most had frontline essential jobs: 23% food service, 14% construction/home maintenance, and 10% cleaning. Overall, 86/157 (55%) of patients lived in neighborhoods home to majority Latinx and African-American populations. Overall, 45/157 (29%) of patients needed ICU care, and 26/157 (17%) required mechanical ventilation; 20/26 (77%) of ventilated patients were successfully extubated, and 137/157 (87%) were discharged home. Median hospitalization duration was 4 days (IQR, 2–10), and only 6/157 (4%) patients died in hospital. Conclusion In San Francisco, where early COVID-19 mitigation was enacted, we report a stark, disproportionate COVID-19 burden on Latinx patients, who accounted for 81% of hospitalizations despite making up only 32% of the patient base and 15% of San Francisco’s total population. Latinx inpatients frequently lived in high-density settings, increasing household risk, and frequently worked essential jobs, potentially limiting the opportunity to effectively distance from others. We also report here favorable clinical outcomes and low overall mortality. However, an effective COVID-19 response must urgently address racial and ethnic disparities. Disclosures All Authors: No reported disclosures

Small molecules that target microtubules (MTs) represent promising therapeutics to treat certain types of cancer, including glioblastoma multiform (GBM). We synthesized modified carbazoles and evaluated their antitumor activity in GBM cells in culture. Modified carbazoles with an ethyl moiety linked to the nitrogen of the carbazole and a carbonyl moiety linked to distinct biaromatic rings exhibited remarkably different killing activities in human GBM cell lines and patient-derived GBM cells, with IC50 values from 67 to >10,000 nM. Measures of the activity of modified carbazoles with tubulin and microtubules coupled to molecular docking studies show that these compounds bind to the colchicine site of tubulin in a unique low interaction space that inhibits tubulin assembly. The modified carbazoles reported here represent novel chemical tools to better understand how small molecules disrupt MT functions and kill devastating cancers such as GBM.

The language that scientists use to frame biological invasions may reveal inherent bias—including how data are interpreted. A frequent critique of invasion biology is the use of value-laden language that may indicate context bias. Here we use a systematic study of language and interpretation in papers drawn from invasion biology to evaluate whether there is a link between the framing of papers and the interpretation of results. We also examine any trends in context bias in biological invasion research. We examined 651 peer-reviewed invasive species competition studies and implemented a rigorous systematic review to examine bias in the presentation and interpretation of native and invasive competition in invasion biology. We predicted that bias in the presentation of invasive species is increasing, as suggested by several authors, and that bias against invasive species would result in misinterpreting their competitive dominance in correlational observational studies compared to causative experimental studies. We indeed found evidence of bias in the presentation and interpretation of invasive species research; authors often introduced research with invasive species in a negative context and study results were interpreted against invasive species more in correlational studies. However, we also found a distinct decrease in those biases since the mid-2000s. Given that there have been several waves of criticism from scientists both inside and outside invasion biology, our evidence suggests that the subdiscipline has somewhat self-corrected apparent biases.

Glioblastoma multiforme is a devastating and intractable type of cancer. Current antineoplastic drugs do not improve the median survival of patients diagnosed with glioblastoma multiforme beyond 14 to 15 months, in part because the blood–brain barrier is generally impermeable to many therapeutic agents. Drugs that target microtubules (MT) have shown remarkable efficacy in a variety of cancers, yet their use as glioblastoma multiforme treatments has also been hindered by the scarcity of brain-penetrant MT-targeting compounds. We have discovered a new alkylindole compound, ST-11, that acts directly on MTs and rapidly attenuates their rate of assembly. Accordingly, ST-11 arrests glioblastoma multiforme cells in prometaphase and triggers apoptosis. In vivo analyses reveal that unlike current antitubulin agents, ST-11 readily crosses the blood–brain barrier. Further investigation in a syngeneic orthotopic mouse model of glioblastoma multiforme shows that ST-11 activates caspase-3 in tumors to reduce tumor volume without overt toxicity. Thus, ST-11 represents the first member of a new class of brain-penetrant antitubulin therapeutic agents. Mol Cancer Ther; 15(9); 2018–29. ©2016 AACR.

Mycotic aneurysms are rare in patients with congenital heart disease, but may occur in those with aortic coarctation and abnormal aortic valve. Rapid diagnosis of mycotic aneurysm is of extreme importance given the significant reported incidence of morbidity and mortality across all age groups. Aortic aneurysm is uncommon before the second decade of life, and here we report a 10-year-old male patient with new diagnosis of aortic coarctation and bicuspid aortic valve, who developed a rapidly enlarging mycotic aneurysm from Streptococcus pneumoniae. Cardiac magnetic resonance imaging was crucial in making the diagnosis, as well as in follow-up.

There are a number of causes of hypothyroidism, which include primary, transient, and secondary causes. Primary causes consist of autoimmune hypothyroidism, also known as Hashimotos thyroiditis, or...

The second most serious neurodegenerative disease is Parkinson’s disease (PD). Over the past several decades, a strong body of evidence suggests that PD can begin years before the hallmark clinical motor symptoms appear. Biomarkers for PD are urgently needed to differentiate between neurodegenerative disorders, screen novel therapeutics, and predict eventual clinical PD before the onset of symptoms. Some clinical evaluations and neuroimaging techniques have been developed in the last several years with some success in this area. Moreover, other strategies have been utilized to identify biochemical and genetic markers associated with PD leading to the examination of PD progression and pathogenesis in cerebrospinal fluid, blood, or saliva. Finally, interesting results are surfacing from preliminary studies using known PD-associated genetic mutations to assess potential premotor PD biomarkers. The current review highlights recent advances and underscores areas of potential advancement.

Glioblastoma multiforme (GBM) is the most common and aggressive brain neoplasm. Treatment options for this cancer are limited, and the five-year survival rate is less than 5%. Cannabinoid compounds have the ability to cross the blood brain barrier (BBB) and selectively kill tumor cells while maintaining a favorable safety profile, making them attractive candidates as novel GBM therapeutics. For example, the cannabinoid agonists WIN55212-2 (WIN-2) and Δ9-tetrahydrocannabinol (THC) induce GBM cell death both in vitro and reduce tumor growth in vivo, while sparing healthy cells. While cannabinoid compounds typically act through two G protein-coupled receptors (GPCR), CB1, and CB2, evidence suggests that WIN-2, an alkylindole (AI) cannabinoid, kills tumor cells through a separate, unknown mechanism. To explore this unknown mechanism, our lab developed a novel series of AI compounds that exhibit reduced affinity to CB1 and CB2 receptors. The model AI compound, ST-11, was found to destabilize microtubules (MTs) and promote both cell cycle arrest in prometaphase and caspase-dependent apoptosis. Recent studies have shown that GBMs are particularly sensitive to mitotic disruption; however, the use of MT-targeting agents is limited by toxic side effects and a general inability to cross the BBB. ST-11 was found to exhibit a promising safety profile in mice and did not induce overt toxicity in any major organs up to its maximal administrable dose of 240 mg/kg. Additionally, ST-11 readily crossed the BBB within 60 min of intraperitoneal injection and dose-dependently induced caspase activation and reduced tumor size in an orthotopic syngeneic glioma mouse model. Our findings suggest that AI compounds such as ST-11 belong to a new class of brain-penetrant MT-targeting agents that preferentially kill tumor cells.

The discovery of novel noncoding RNAs has been among the most exciting recent developments in biology. It has been hypothesized that there is, in fact, an abundance of functional noncoding RNAs (ncRNAs) with various catalytic and regulatory functions. However, the inherent signal for ncRNA is weaker than the signal for protein coding genes, making these harder to identify. We consider the following problem: Given an RNA sequence with a known secondary structure, efficiently detect all structural homologs in a genomic database by computing the sequence and structure similarity to the query. Our approach, based on structural filters that eliminate a large portion of the database while retaining the true homologs, allows us to search a typical bacterial genome in minutes on a standard PC. The results are two orders of magnitude better than the currently available software for the problem. We applied FastR to the discovery of novel riboswitches, which are a class of RNA domains found in the untranslated regions. They are of interest because they regulate metabolite synthesis by directly binding metabolites. We searched all available eubacterial and archaeal genomes for riboswitches from purine, lysine, thiamin, and riboflavin subfamilies. Our results point to a number of novel candidates for each of these subfamilies and include genomes that were not known to contain riboswitches.