Pentagon Found Daily, Metagenomic Detection of Novel Bioaerosol Threats to Be Cost-Prohibitive: Can Virtualization and AI Make It Cost-Effective?

In 2022, the Pentagon Force Protection Agency found threat agnostic detection of novel bioaerosol threats to be "not feasible for daily operations" due to the cost of reagents used for metagenomics, cost of sequencing instruments, and cost of labor for subject matter experts to analyze bioinformatics. Similar operational difficulties might extend to many of the 280,000 buildings (totaling 2.3 billion square feet) at 5,000 secure US Department of Defense military sites, 250 Navy ships, as well as many civilian buildings. These economic barriers can still be addressed in a threat agnostic manner by dynamically pooling samples from dry filter units, called spike-triggered virtualization, whereby pooling and sequencing depth are automatically modulated based on novel biothreats in the sequencing output. By running at a high average pooling factor, the daily and annual cost per dry filter unit can be reduced by 10 to 100 times depending on the chosen trigger thresholds. Artificial intelligence can further enhance the sensitivity of spike-triggered virtualization. The risk of infection during the 12- to 24-hour window between a bioaerosol incident and its detection remains, but in some cases it can be reduced by 80% or more with high-speed indoor air cleaning exceeding 12 air changes per hour, which is similar to the rate of air cleaning in passenger airplanes in flight. That level of air changes per hour or higher is likely to be cost-prohibitive using central heating ventilation and air conditioning systems, but it can be achieved economically by using portable air filtration in rooms with typical ceiling heights (less than 10 feet) for a cost of approximately $0.50 to $1 per square foot for do-it-yourself units and $2 to $5 per square foot for high-efficiency particulate air filters.

Can 10× cheaper, lower-efficiency particulate air filters and box fans complement High-Efficiency Particulate Air (HEPA) purifiers to help control the COVID-19 pandemic?

Public health departments such as CDC and California Department of Public Health (CA-DPH) advise HEPA-purifiers to limit transmission of SARS-CoV-2 indoor spaces. CA-DPH recommends air exchanges per hour (ACH) of 4-6 air for rooms with marginal ventilation and 6-12 in classrooms often necessitating multiple HEPA-purifiers per room, unaffordable in under-resourced community settings. Pressure to seek cheap, rapid air filtration resulted in proliferation of lower-cost, Do-It-Yourself (DIY) air purifiers whose performance is not well characterized compared to HEPA-purifiers. Primary metrics are clean air delivery rate (CADR), noise generated (dBA), and affordability ($$). CADR measurement often requires hard-to-replicate laboratory experiments with generated aerosols. We use simplified, low-cost measurement tools of ambient aerosols enabling scalable evaluation of aerosol filtration efficiencies (0.3 to 10 µm), estimated CADR, and noise generation to compare 3 HEPA-purifiers and 9 DIY purifier designs. DIY purifiers consist of one or two box fans coupled to single MERV 13-16 filters (1″-5″ thick) or quad filters in a cube. Accounting for reduced filtration efficiency of MERV 13-16 filters (versus HEPA) at the most penetrating particle size of 0.3 µm, estimated CADR of DIY purifiers using 2″ (67%), 4″ (66%), and 5″ (85%) filters at lowest fan speed was 293 cfm ($35), 322 cfm ($58), and 405 cfm ($120) comparable to best-in-class, low-noise generating HEPA-purifier running at maximum speed with at 282 cfm ($549). Quad filter designs, popularly known Corsi-Rosenthal boxes, achieved gains in estimated CADR below 80% over single filter designs, less than the 100% gain by adding a second DIY purifier. Replacing one of the four filters with a second fan resulted in gains of 125%-150% in estimated CADR. Tested DIY alternatives using lower-efficiency, single filters compare favorably to tested HEPA-purifiers in estimated CADR, noise generated at five to ten times lower cost, enabling cheap, rapid aerosol removal indoors.

Does Physical Activity Play a Role in the Efficacy of RegoNivo for MSS-mCRC?

BACKGROUND: In 2019, researchers reported a remarkable 33% response rate and a median progression free survival of almost 8 months in a study of Regorafenib and Nivolumab (RegoNivo) with 24 Japanese patients with chemo-refractory MSS-mCRC. These clinical outcomes were subsequently not replicated in clinical trials in North America. One hypothesis that has been put forth is that trials in North America had a higher percentage of patients with liver metastases who are less likely to respond to Regorafenib and Nivolumab. We propose an alternate hypothesis reflected by ECOG Performance Status = 0. METHODS: We reexamined the available trial data on RegoNivo for MSS-mCRC in the original Japanese trial and compared it to subsequent clinical trials of the same combination and setting in North America. RESULTS: 100% of patients on the original Japanese trial were ECOG PS = 0 whereas those in the subsequent trials in North America included a majority of patients with ECOG PS = 1. The percentage of patients with liver metastases is not as clearly different among these trials compared to ECOG PS 0. CONCLUSIONS: ECOG PS may represent a composite marker of patient physical activity and/or fitness and disease biology. Although ECOG PS and physical activity are not completely the same, ECOG PS and physical activity of patients has not been fully investigated in the context of response to RegoNivo. Alternatively, it is possible that poor ECOG PS may also reflect unfavorable tumor biology, and such tumors might progress before RegoNivo has a chance to provide clinical benefit.

We need to bring R0 < 1 to treat cancer too.

If each cancer cell produces on average more than one cancer cell, we see a net growth of the tumors and metastases and vice versa. We review recent clinical results for microsatellite stable metastatic colorectal cancer (MSS-mCRC) suggesting immunotherapy combinations with personalized vaccines, checkpoint inhibitors, targeted therapies, multikinase inhibitors, chemotherapies, and radiation that simultaneously slow cancer cell growth rate and enhance T cell killing rate of cancer cells may in future synergize to control the disease.

Using noun phrases for navigating biomedical literature on Pubmed: how many updates are we losing track of?

Author-supplied citations are a fraction of the related literature for a paper. The "related citations" on PubMed is typically dozens or hundreds of results long, and does not offer hints why these results are related. Using noun phrases derived from the sentences of the paper, we show it is possible to more transparently navigate to PubMed updates through search terms that can associate a paper with its citations. The algorithm to generate these search terms involved automatically extracting noun phrases from the paper using natural language processing tools, and ranking them by the number of occurrences in the paper compared to the number of occurrences on the web. We define search queries having at least one instance of overlap between the author-supplied citations of the paper and the top 20 search results as citation validated (CV). When the overlapping citations were written by same authors as the paper itself, we define it as CV-S and different authors is defined as CV-D. For a systematic sample of 883 papers on PubMed Central, at least one of the search terms for 86% of the papers is CV-D versus 65% for the top 20 PubMed "related citations." We hypothesize these quantities computed for the 20 million papers on PubMed to differ within 5% of these percentages. Averaged across all 883 papers, 5 search terms are CV-D, and 10 search terms are CV-S, and 6 unique citations validate these searches. Potentially related literature uncovered by citation-validated searches (either CV-S or CV-D) are on the order of ten per paper--many more if the remaining searches that are not citation-validated are taken into account. The significance and relationship of each search result to the paper can only be vetted and explained by a researcher with knowledge of or interest in that paper.