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Manifestations of two solar flares of March 2022 were studied over Mexico. The flare effects in the lower ionosphere had a ~3 min delay from the X1.3-flare onset and ~5 min from the M9.6-flare onset. The maximal impact on the HF signal amplitude was ~(14–15) min after the onset of both flares. The X1.3-flare provoked the shortwave fadeout during ~6 min. The effects in the lower ionosphere lasted longer than the flares and the effects at the F2 region and higher altitudes only during the flares. The interpretation of results showed the following. (1) Based on the absorption level estimated with minimum frequency and signal amplitude on ionograms, the major role of X-ray radiation in the electron concentration increase in the lower ionosphere was confirmed. At the same time, the EUV radiation impact on the lower ionosphere cannot be totally discarded. The lower ionosphere recovery began before and lasted after the X1.3-flare end, being more rapid at Eglin than in Mexico. During M9.6-flare, the responses at the two observation points were rather synchronized due to the more similar illumination conditions at the two meridians. (2) According to the dI variations characterizing the F2 region and higher, the M9.6-flare provoked medium-scale and the X1.3-flare provoked both medium- and small-scale ionospheric irregularities. The response duration corresponded to the dI series filtered with (10–20) min windows. The dI curve during the flares was characterized by the И-form and depended more on the active region position and the flare class than on the solar zenith angle. The available data do not allow us to unambiguously identify the reason for the negative dI: the applied filtering procedure or the physical effect. (3) During both flares, the major EUV impact on the lower ionosphere was by the flux at 133.5 nm and on the F2 region and higher altitudes at 25.6 nm. In addition, during the M9.6-flare, EUV 28.4, 30.4 and 121.6 nm spectral bands also played an important role in the F2 response. During the X1.3-flare, the EUV 25.6 nm flux and X-ray flux impacts on the F2 region were of the same level. The weakest impact was caused by the emission in the EUV 28.4 nm spectral band on the absorption in the lower ionosphere during both flares and on the electron density in the F2 region and higher during the X1.3-flare.

Many peptide hormones form an alpha-helix upon binding their receptors1–4, and sensitive detection methods for them could contribute to better clinical management.De novoprotein design can now generate binders with high affinity and specificity to structured proteins5,6. However, the design of interactions between proteins and short helical peptides is an unmet challenge. Here, we describe parametric generation and deep learning-based methods for designing proteins to address this challenge. We show that with the RFdiffusiongenerative model, picomolar affinity binders can be generated to helical peptide targets either by noising and then denoising lower affinity designs generated with other methods, or completelyde novostarting from random noise distributions; to our knowledge these are the highest affinity designed binding proteins against any protein or small molecule target generated directly by computation without any experimental optimization. The RFdiffusiondesigns enable the enrichment of parathyroid hormone or other bioactive peptides in human plasma and subsequent detection by mass spectrometry, and bioluminescence-based protein biosensors. Capture reagents for bioactive helical peptides generated using the methods described here could aid in the improved diagnosis and therapeutic management of human diseases.7,8

Purpose Oral and maxillofacial surgeons (OMSs) must manage postoperative pain control for patients who take illicit substances. The purpose of this study was to measure and compare the amount of opioid prescribing between patients with and without self-reported substance use history (SUH) by OMSs after third molar (M3) removal. Materials and Methods The investigators implemented a retrospective cohort study and enrolled a sample of subjects who had M3 removal between January 1, 2019 through December 31, 2019. The primary predictor variable was SUH coded as yes (SUH+) or no (SUH-). The primary and secondary outcome variables were prescribed morphine milligram equivalents (MMEs) and number of postoperative visits due to inadequate pain control (IPC), respectively. Other variables were age, gender, payor, provider, anesthesia, and procedure specific. Descriptive, bivariate, and multiple linear regression models were computed. Results The sample included 1,112 subjects with a mean age of 25 ± 9 years; 61.2% were female. Of the 1,112 subjects, 198 (17.8%) reported a SUH. Mean MMEs were 70.9 ± 27.9 and 63.4 ± 28.8 in the SUH+ and SUH- groups, respectively (P ≤ .001). An adjusted linear regression model showed a non-significant association between SUH and MMEs prescribed (P = .50). The study showed a non-significant increase (P = .15) in the proportion of patients with IPC in the SUH- group (4.1%) versus the SUH+ group (2.0%). Conclusions The results suggest that 10% more opioids were prescribed for postoperative pain after M3 removal for patients with SUH, though after adjustment, the amount may not be clinically significant. Postoperative pain management after M3 removal in patients with SUH, on average, can be managed in a similar manner as for patients without SUH.

The multisubunit protein assemblies that play critical roles in biology are the result of evolutionary selection for function of the entire assembly, and hence the subunits in structures such as icosahedral viral capsids often fit together with remarkable shape complementarity1,2. In contrast, the large multisubunit assemblies that have been created by de novo protein design, notably the icosahedral nanocages used in a new generation of potent vaccines3–7, have been built by first designing symmetric oligomers with cyclic symmetry and then assembling these into nanocages while keeping the internal structure fixed8–14, which results in more porous structures with less extensive shape matching between the components. Such hierarchical “bottom-up” design approaches have the advantage that one interface can be designed and validated in the context of the cyclic oligomer building block15,16, but the disadvantage that the structural and functional features of the assemblies are limited by the properties of the predesigned building blocks. To overcome this limitation, we set out to develop a “top-down” reinforcement learning based approach to protein nanomaterial design in which both the structures of the subunits and the interactions between them are built up coordinately in the context of the entire assembly. We developed a Monte Carlo tree search (MCTS) method17,18 which assembles protein monomer structures in the context of an overall architecture guided by a loss function which enables specification of any desired overall structural properties such as shape and porosity. We demonstrate the power of the approach by designing hyperstable icosahedral assemblies more compact than any previously observed protein icosahedral structure (designed or naturally occurring), that have very low porosity and are robust to fusion and display of proteins as complex as influenza hemagglutinin. CryoEM structures of two designs are very close to the computational design models. Our top-down reinforcement learning approach should enable the design of a wide variety of complex protein nanomaterials by direct optimization of overall system properties.

In late 2020, models predicted that a strong La Niña would take place for the first time since 2013, and we assessed whether physical and biological indicators in 2021 were similar to past La Niñas in the California Current Ecosystem (CCE). The Pacific Decadal Oscillation and Oceanic Niño Index indeed remained negative throughout 2021; the North Pacific Gyre Oscillation Index, however, remained strongly negative. The seventh largest marine heatwave on record was unexpectedly present from April to the end of 2021; however, similar to past La Niñas, this mass of warm water mostly remained seaward of the continental shelf. As expected from past La Niñas, upwelling and chlorophyll were mostly high and sea surface temperature was low throughout the CCE; however, values were close to average south of Point Conception. Similar to past La Niñas, abundances of lipid-rich, northern copepods off Oregon increased. In northern California, unlike past La Niñas, the body size of North Pacific krill (Euphausia pacifica) was close to average. Predictably, overall krill abundance was above average in far northern California but, unexpectedly, below average south of Cape Mendocino. Off Oregon, similar to past La Niñas, larval abundances of three of six coastal species rose, while five of six southern/offshore taxa decreased in 2021. Off California, as expected based on 2020, Northern Anchovy (Engraulis mordax) were very abundant, while Pacific Sardine (Sardinops sagax) were low. Similar to past La Niñas, market squid (Doryteuthis opalescens) and young of the year (YOY) Pacific Hake (Merluccius pacificus), YOY sanddabs (Citharichthys spp.), and YOY rockfishes (Sebastes spp.) increased. Southern mesopelagic (e.g., Panama lightfish Vinciguerria lucetia, Mexican lampfish Triphoturus mexicanus) larvae decreased as expected but were still well above average, while northern mesopelagic (e.g., northern lampfish Stenobrachius leucopsarus) larvae increased but were still below average. In line with predictions, most monitored bird species had above-average reproduction in Oregon and California. California sea lion (Zalophus californianus) pup count, growth, and weight were high given the abundant Anchovy forage. The CCE entered an enduring La Niña in 2021, and assessing the responses of various ecosystem components helped articulate aspects of the system that are well understood and those that need further study.

Multiple reports have linked COVID-19 infection with sudden sensorineural hearing loss (SSNHL), although other studies have failed to demonstrate this association. The current study was conceived to examine the rates of SSNHL across a large, principally national, population by characterizing the rate of transtympanic injections for SSNHL during the pandemic.Retrospective review of all patients that underwent transtympanic injection from 2019 to 2020.Covering a unique beneficiary population of 9.6 million individuals of all ages in the United States, a statistically significant decrease in transtympanic injections for SSNHL was performed from 2019 to 2020 (p = 0.04, IRR = 0.91, 95 % CI = 0.84-0.99). No patient receiving a transtympanic injection also had a COVID-19 diagnosis.These findings support the idea that COVID-19 infections do not clinically significantly increase patients' risk of developing SSNHL. In fact, the decreased exposure through social isolation to other common viruses implicated in causing SSNHL may have actually led to a lower rate of SSNHL during the pandemic.

Young patients, including pediatric, adolescent, and young adult (YA) patients, are most likely to benefit from the reduced integral dose of proton beam radiation therapy (PBT) resulting in fewer late toxicities and secondary malignancies. This study sought to examine insurance approval and appeal outcomes for PBT among YA patients compared with pediatric patients at a large-volume proton therapy center.We performed a cross-sectional cohort study of 284 consecutive patients aged 0 to 39 years for whom PBT was recommended in 2018 through 2019. Pediatric patients were defined as aged 0 to 18 years and YA patients 19 to 39 years. Rates of approval, denials, and decision timelines were calculated. Tumor type and location were also evaluated as factors that may influence insurance decisions.A total of 207 patients (73%) were approved for PBT at initial request. YA patients (n = 68/143, 48%) were significantly less likely to receive initial approval compared with pediatric patients (n = 139/141; 99%) (P.001). Even after 47% (n = 35 of 75) of the PBT denials for YA patients were overturned, YAs had a significantly lower final PBT approval (72% vs pediatric 99%; P.001). The median wait time was also significantly longer for YA patients (median, 8 days; interquartile range [IQR] 3-17 vs median, 2 days; IQR, 0-6; P.001). In those patients requiring an appeal, the median wait time was 16 days (IQR, 9-25).Given the decades of survivorship of YA patients, PBT is an important tool to reduce late toxicities and secondary malignancies. Compared with pediatric patients, YA patients are significantly less likely to receive insurance approval for PBT. Insurance denials and subsequent appeal requests result in significant delays for YA patients. Insurers need to re-examine their policies to include expedited decisions and appeals and removal of arbitrary age cutoffs so that YA patients can gain easier access to PBT. Furthermore, consensus guidelines encouraging greater PBT access for YA may be warranted from both medical societies and/or AYA experts.