Three lineages (BA.1, BA.2 and BA.3) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern predominantly drove South Africa’s fourth Coronavirus Disease 2019 (COVID-19) wave. We have now identified two new lineages, BA.4 and BA.5, responsible for a fifth wave of infections. The spike proteins of BA.4 and BA.5 are identical, and similar to BA.2 except for the addition of 69–70 deletion (present in the Alpha variant and the BA.1 lineage), L452R (present in the Delta variant), F486V and the wild-type amino acid at Q493. The two lineages differ only outside of the spike region. The 69–70 deletion in spike allows these lineages to be identified by the proxy marker of S-gene target failure, on the background of variants not possessing this feature. BA.4 and BA.5 have rapidly replaced BA.2, reaching more than 50% of sequenced cases in South Africa by the first week of April 2022. Using a multinomial logistic regression model, we estimated growth advantages for BA.4 and BA.5 of 0.08 (95% confidence interval (CI): 0.08–0.09) and 0.10 (95% CI: 0.09–0.11) per day, respectively, over BA.2 in South Africa. The continued discovery of genetically diverse Omicron lineages points to the hypothesis that a discrete reservoir, such as human chronic infections and/or animal hosts, is potentially contributing to further evolution and dispersal of the virus.

We present a global QCD analysis of spin-dependent parton distribution functions (PDFs) that includes the latest polarized W-lepton production data from the STAR collaboration at RHIC. These data allow the first data-driven extraction of a nonzero polarized light quark sea asymmetry Δu¯−Δd¯ within a global QCD framework with minimal theoretical assumptions.

Purpose of review: PET has emerged as method to determine the location and extent of disease activity in sarcoidosis. As most clinicians do not routinely utilize PET in the management of sarcoidosis, an understanding of the imaging technique is needed to comprehend the impact that PET abnormalities have on diagnosis, prognosis, and treatment. Recent findings: Although PET can detect inflammation because of sarcoidosis throughout the body, it is most often utilized for the diagnosis of cardiac sarcoidosis for which it may provide information about prognosis and adverse events. Whenever PET is combined with cardiac magnetic resonance (CMR), clinicians may be able to increase the diagnostic yield of imaging. Furthermore, PET abnormalities have the potential to be utilized in the reduction or augmentation of therapy based on an individual's response to treatment. Although various biomarkers are used to monitor disease activity in sarcoidosis, an established and reproducible relationship between PET and biomarkers does not exist. Summary: PET has the potential to improve the diagnosis of sarcoidosis and alter treatment decisions but prospective trials are needed to define the role of PET while also standardizing the performance and interpretation of the imaging modality.

Aim: The mitochondria are highly plastic and dynamic organelles; mitochondrial dysfunction has been reported to play causative roles in diabetes, cardiovascular diseases, and nonalcoholic fatty liver disease (NAFLD). However, the relationship between mitochondrial fission and NAFLD pathogenesis remains unknown. We aimed to investigate whether alterations in mitochondrial fission could play a role in the progression of NAFLD. Methods: Mice were fed a standard diet or choline-deficient, L-amino acid-defined (CDAA) diet with vehicle or mitochondrial division inhibitor-1. Results: Substantial enhancement of mitochondrial fission in hepatocytes was triggered by 4 weeks of feeding and was associated with changes reflecting the early stage of human nonalcoholic steatohepatitis (NASH), steatotic change with liver inflammation, and hepatocyte ballooning. Excessive mitochondrial fission inhibition in hepatocytes and lipid metabolism dysregulation in adipose tissue attenuated liver inflammation and fibrogenesis but not steatosis and the systemic pathological changes in the early and chronic fibrotic NASH stages (4- and 12-week CDAA feeding). These beneficial changes due to the suppression of mitochondrial fission against the liver and systemic injuries were associated with decreased autophagic responses and endoplasmic reticulum stress in hepatocytes. Injuries to other liver cells, such as endothelial cells, Kupffer cells, and hepatic stellate cells, were also attenuated by the inhibition of mitochondrial fission in hepatocytes. Conclusions: Taken together, these findings suggest that excessive mitochondrial fission in hepatocytes could play a causative role in NAFLD progression by liver inflammation and fibrogenesis through altered cell cross-talk. This study provides a potential therapeutic target for NAFLD.

We present the first simultaneous global QCD analysis of spin-dependent parton distribution functions alongside their spin-averaged counterparts and pion, kaon, and unidentified hadron fragmentation functions. This analysis includes all data relevant for constraining the polarized light quark sea asymmetry Δ¯u−Δ¯d, in particular the latest polarized W-lepton production data from the STAR Collaboration at RHIC and semi-inclusive deep inelastic scattering data from COMPASS, allowing the most robust extraction available with minimal theoretical assumptions. We also extract a self-consistent set of antiquark polarization ratios Δ¯u/¯u and Δ¯d/¯d and determine the signs of the truncated contributions to the proton spin from the light antiquarks.

Introduction: Small burns with a total body surface area (TBSA) of < 20% account for the large majority (92%) of burn injury hospital admissions. Autologous skin cell suspension (ASCS) is a novel treatment for acute thermal burn injuries – including small burns -- that is associated with significantly lower donor skin requirements than split-thickness skin grafts, the traditional standard of care (SOC). The ASCS treatment indication was recently expanded from adult patients to include pediatric patients. Previously modeled analyses suggested that ASCS use is associated with a lower hospital length of stay (LOS) and costs savings versus SOC. This study evaluated whether real-world data (RWD) corroborate these findings in small burns and in both adult and pediatric populations. Methods: Data were collected from January 2019 through August 2020 from 500 facilities in the United States. Adult patients (age ≥ 21) and pediatric patients (< age 21) receiving inpatient burn treatment with ASCS were identified and matched to patients receiving SOC based on sex, age, TBSA < 20%, and comorbidities. Based on typical BEACON model outcomes, LOS was assumed to account for 70% of total costs and was used as a proxy to assess the data. LOS was assumed to cost $7,554 per day. Mean LOS and costs were calculated for the ASCS and SOC adult and pediatric cohorts. The incremental revenue associated with changes in inpatient capacity was also analyzed. Results: A total of 151 ASCS and 2,243 SOC adult cases and 19 ASCS and 341 SOC pediatric cases were identified. In adults, the SOC cohort had a higher percentage of patients with TBSA < 20% than the ASCS cohort (82.9% vs. 55.0%). For small burns, sixty-three matches were made for each adult cohort, and seven matches were made for each pediatric cohort. For adults, LOS was 18.5 days with ASCS use and 20.6 days with SOC use (difference: 2.1 days [10.2%]). For pediatrics, the ASCS LOS was 18.6 days, and the SOC LOS was 21.4 days (difference: 2.9 days [15.4%]). This difference led to cost savings of $15,587.62 per adult ASCS patient. Total cost savings with ASCS adult patients were $22,268.03 per patient. The reduced LOS with ASCS adult patients resulted in an increased capacity of 2.0 inpatients per bed per year, which was estimated to increase hospital revenue by $83,894 per burn unit bed annually. Pediatric cost results and savings were similar. Conclusion: This RWD analysis shows that small burn treatment with ASCS is associated with reduced LOS and substantial cost savings compared with SOC in both adult and pediatric populations, supporting the validity of previous model projections. ASCS use may also significantly increase hospital revenue related to increased inpatient capacity.

Background: Historically, stapedectomy complication rates are quoted as 1% profound postoperative sensorineural hearing loss (SNHL), 5%–10% nonprofound SNHL, and 5%–10% revision surgery. Objective: We sought to reassess rates of post-stapedotomy complications based on our experience using contemporary surgical technique. Methods: A retrospective case series was carried out at an academic tertiary referral center. Adult patients undergoing stapedotomy from 2013 to 2020 were included. Primary outcomes were rates of hearing loss and revision surgery. Rates of dizziness, tinnitus, dysgeusia, and proportions of patients who achieved air-bone gap (ABG) closure at 8–12 weeks postoperatively were also assessed. Results: Four hundred sixty-eight stapedotomies in 399 patients with a median follow-up duration of 99 days (range, 11–5134) were reviewed. One patient (0.21%) suffered profound SHNL and 15 (3.20%) patients suffered nonprofound SNHL. The revision rate for stapedotomies from our institution was 4.49% (21 total revision surgeries). In 277 operations (59.19%), the patient had closure of the ABG within 10 dB. A further 132 (28.21%) had closure of the ABG between 10 and 20 dB. Air pure-tone audiometry scores improved by an average of 25.03 dB. Eighty-three (17.74%) patients complained of postoperative dizziness, which resolved by the time of the first follow-up appointment in all but 26 (5.56%). Seventeen patients (3.63%) complained of tinnitus, and 22 (4.70%) complained of dysgeusia. Conclusions: SNHL, complications, and revision rates for stapedotomy in the modern era may be substantially lower than those currently presented to patients based on classic techniques and historical data.

Introduction: Experience of sexual violence (SV) is prevalent among the Veteran population and associated with many negative mental and physical health outcomes including suicidal behavior, obesity, post-traumatic stress disorder, anxiety, depression, and poor sexual and reproductive functioning. Although Veterans of any gender may experience SV, women Veterans are particularly at risk. Research on SV among Veterans has focused primarily on the experience of SV during military service (military sexual trauma, MST), although Veterans may also experience SV prior to and following military service. The aim of the current study was to construct a more comprehensive method of identifying SV among Veterans Health Administration (VHA) patients as documented in medical records in a national cohort of 325,907 Veterans who used VHA care between 2000 and 2018 in order to inform future research in this area. Method: We used three indicators to identify SV in VHA medical records: (a) the MST screen, (b) the sexual violence item of the intimate partner violence (IPV) screen, and (c) International Classification of Disorders (ICD) codes (versions 9 and 10) representing adult sexual abuse and assault. Univariate descriptive analyses were conducted to determine the exclusivity and overlap of the SV measures. Results: The universal MST screen was the most commonly identified indicator of SV in the data. However, including the IPV and ICD indicators identified an additional 5% of Veterans who had experienced SV, accounting for thousands of patients. Discussion: The results of the current study indicate that using the three-pronged approach of SV collection is a more comprehensive method of identifying patient SV experience through VHA medical records and contributes uniquely to the methodology of studying social factors’ impact on health care. Clinical screening and documentation of SV allow for the assessment of health impacts and trends through examination of medical records data.

The study of biologically relevant molecules and their interaction with external stimuli on a single molecular scale is of high importance due to the availability of distributed rather than averaged information. Surface enhanced Raman scattering (SERS) provides direct chemical information, but is rather challenging on the single molecule (SM) level, where it is often assumed to require a direct contact of analyte molecules with the metal surface. Here, we detect and investigate the molecular states of single hemin by SM-SERS. A DNA aptamer based G-quadruplex mediated recognition of hemin directs its placement in the SERS hot-spot of a DNA Origami Nanofork Antenna (DONA). The configuration of the DONA structure allows the molecule to be trapped at the plasmonic hot-spot preferentially in no-contact configuration with the metal surface. Owing to high field enhancement at the plasmonic hot spot, the detection of a single folded G-quadruplex becomes possible. For the first time, we present a systematic study by SM-SERS where most hemin molecule adopt a high spin and oxidation state (III) that showed state crossover to low spin upon strong-field-ligand binding. The present study therefore, provides a platform for studying biologically relevant molecules and their properties at SM sensitivity along with demonstrating a conceptual advancement towards successful monitoring of single molecular chemical interaction using DNA aptamers.

Understanding and communicating uncertainty is a key skill needed in the practice of science. However, there has been little research on the instruction of uncertainty in undergraduate science education. Our team designed a module within an online geoscience field course which focused on explicit instruction around uncertainty and provided students with an uncertainty rating scale to record and communicate their uncertainty with a common language. Students then explored a complex, real-world geological problem about which expert scientists had previously made competing claims through geologic maps. Provided with data, expert uncertainty ratings, and the previous claims, students made new geologic maps of their own and presented arguments about their claims in written form. We analyzed these reports along with assessments of uncertainty. Most students explicitly requested geologists’ uncertainty judgments in a post-course assessment when asked why scientists might differ in their conclusions and/or utilized the rating scale unprompted in their written arguments. Through the examination of both pre- and post-course assessments of uncertainty and students’ course-based assessments, we argue that explicit instruction around uncertainty can be introduced during undergraduate coursework and could facilitate geoscience novices developing into practicing geoscientists.