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Annual epidemics of seasonal influenza cause hundreds of thousands of deaths, high levels of morbidity, and substantial economic loss. Yet, global influenza circulation has been heavily suppressed by public health measures and travel restrictions since the onset of the COVID-19 pandemic. Notably, the influenza B/Yamagata lineage has not been conclusively detected since April 2020, and A(H3N2), A(H1N1), and B/Victoria viruses have since circulated with considerably less genetic diversity. Travel restrictions have largely confined regional outbreaks of A(H3N2) to South and Southeast Asia, B/Victoria to China, and A(H1N1) to West Africa. Seasonal influenza transmission lineages continue to perish globally, except in these select hotspots, which will likely seed future epidemics. Waning population immunity and sporadic case detection will further challenge influenza vaccine strain selection and epidemic control. We offer a perspective on the potential short- and long-term evolutionary dynamics of seasonal influenza and discuss potential consequences and mitigation strategies as global travel gradually returns to pre-pandemic levels. COVID-19 control measures have suppressed circulation of other infections including influenza. Here, the authors analyse WHO global influenza sequence and case report data and describe changes in the phylogenetic and geographic distribution of influenza lineages during the COVID-19 pandemic.

Head trauma from abuse, including shaken baby syndrome, is a devastating and potentially lethal form of infant physical abuse first recognized in the early 1970s. What has been less recognized is the role of the early increase in crying in otherwise normal infants in the first few months of life as a trigger for the abuse. In part, this is because infant crying, especially prolonged unsoothable crying, has been interpreted clinically as something wrong with the infant, the infant's caregiver, or the interactions between them. Here, we review an alternative developmental interpretation, namely, that the early increase in crying is a typical behavioral development in normal infants and usually does not reflect anything wrong or abnormal. We also review evidence indicating that this normal crying pattern is the most common trigger for abusive head trauma (AHT). Together, these findings point to a conceptualization of AHT as the consequence of a failure in an otherwise common, iterative, and developmentally normal infant–caregiver interaction. They also imply that there is a window of opportunity for prevention of AHT, and potentially other forms of infant abuse, through a public health primary universal prevention strategy aimed at changing knowledge and behaviors of caregivers and society in general concerning normal development of infants and the significance of early increased infant crying. If effective, there may be important implications for prevention of infant abuse nationally and internationally.

Assembly of the hair bundle, the sensory organelle of the inner ear, depends on differential growth of actin-based stereocilia. Separate rows of stereocilia, labeled 1 through 3 from tallest to shortest, lengthen or shorten during discrete time intervals during development. We used lattice structured illumination microscopy and surface rendering to measure dimensions of stereocilia from mouse apical inner hair cells during early postnatal development; these measurements revealed a sharp transition at postnatal day 8 between stage III (row 1 and 2 widening; row 2 shortening) and stage IV (final row 1 lengthening and widening). Tip proteins that determine row 1 lengthening did not accumulate simultaneously during stages III and IV; while the actin-bundling protein EPS8 peaked at the end of stage III, GNAI3 peaked several days later—in early stage IV—and GPSM2 peaked near the end of stage IV. To establish the contributions of key macromolecular assemblies to bundle structure, we examined mouse mutants that eliminated tip links ( Cdh23 v2J or Pcdh15 av3J ), transduction channels ( Tmie KO ), or the row 1 tip complex ( Myo15a sh2 ). Cdh23 v2J/v2J and Pcdh15 av3J/av3J bundles had adjacent stereocilia in the same row that were not matched in length, revealing that a major role of these cadherins is to synchronize lengths of side-by-side stereocilia. Use of the tip-link mutants also allowed us to distinguish the role of transduction from effects of transduction proteins themselves. While levels of GNAI3 and GPSM2, which stimulate stereocilia elongation, were greatly attenuated at the tips of Tmie KO/KO row 1 stereocilia, they accumulated normally in Cdh23 v2J/v2J and Pcdh15 av3J/av3J stereocilia. These results reinforced the suggestion that the transduction proteins themselves facilitate localization of proteins in the row 1 complex. By contrast, EPS8 concentrates at tips of all Tmie KO/KO , Cdh23 v2J/v2J , and Pcdh15 av3J/av3J stereocilia, correlating with the less polarized distribution of stereocilia lengths in these bundles. These latter results indicated that in wild-type hair cells, the transduction complex prevents accumulation of EPS8 at the tips of shorter stereocilia, causing them to shrink (rows 2 and 3) or disappear (row 4 and microvilli). Reduced rhodamine-actin labeling at row 2 stereocilia tips of tip-link and transduction mutants suggests that transduction’s role is to destabilize actin filaments there. These results suggest that regulation of stereocilia length occurs through EPS8 and that CDH23 and PCDH15 regulate stereocilia lengthening beyond their role in gating mechanotransduction channels.

Rhabdomyosarcoma (RMS) is a family of soft tissue cancers that are related to the skeletal muscle lineage and predominantly occur in children and young adults. A specific chromosomal translocation t(2;13)(q35;q14) that gives rise to the chimeric oncogenic transcription factor PAX3-FOXO1 has been identified as a hallmark of the aggressive alveolar subtype of RMS. PAX3-FOXO1 cooperates with additional molecular changes to promote oncogenic transformation and tumorigenesis in various human and murine models. Its expression is generally restricted to RMS tumor cells, thus providing a very specific target for therapeutic approaches for these RMS tumors. In this article, we review the recent understanding of PAX3-FOXO1 as a transcription factor in the pathogenesis of this cancer and discuss recent developments to target this oncoprotein for treatment of RMS.

The innate immune system is the host’s first line of immune defence against any invading pathogen. To establish an infection in a human host the influenza virus must replicate in epithelial cells of the upper respiratory tract. However, there are several innate immune mechanisms in place to stop the virus from reaching epithelial cells. In addition to limiting viral replication and dissemination, the innate immune system also activates the adaptive immune system leading to viral clearance, enabling the respiratory system to return to normal homeostasis. However, an overzealous innate immune system or adaptive immune response can be associated with immunopathology and aid secondary bacterial infections of the lower respiratory tract leading to pneumonia. In this review, we discuss the mechanisms utilised by the innate immune system to limit influenza virus replication and the damage caused by influenza viruses on the respiratory tissues and how these very same protective immune responses can cause immunopathology.

Primary high-grade infiltrating gliomas of the spinal cord are rare, with prior series including limited numbers of cases and reporting poor outcomes. Additionally, the molecular profile of high-grade infiltrating gliomas of the spinal cord has not been well characterized. We identified 13 adult patients whose surgery had been performed at our institution over a 26-year-period. Radiologically, nine cases harbored regions of post-contrast enhancement. Existing slides were reviewed, and when sufficient tissue was available, immunohistochemical stains (IDH1-R132H, H3-K27M, H3K27-me3, ATRX, p53 and BRAF-V600E), and a targeted 150-gene neuro-oncology next-generation sequencing panel were performed. The 13 patients included 11 men and 2 women with a median age of 38 years (range = 18–69). Histologically, all were consistent with an infiltrating astrocytoma corresponding to 2016 WHO grades III ( n  = 5) and IV ( n  = 8). By immunohistochemistry, six cases were positive for H3K27M, all showing concomitant loss of H3K27-me3. Next-generation sequencing was successfully performed in ten cases. Next-generation sequencing studies were successfully performed in four of the cases positive for H3K27M by immunohistochemistry, and all were confirmed as H3F3A K27M-mutant. Additional recurrent mutations identified included those of TERT promoter ( n  = 3), TP53 ( n  = 5), PPM1D ( n  = 3), NF1 ( n  = 3), ATRX ( n  = 2), and PIK3CA ( n  = 2). No HIST1H3B , HIST1H3C , IDH1 , IDH2 , or BRAF mutations were detected. Ten patients have died since first surgery, with a median survival of 13 months and 1 year of 46%. Median survival was 48.5 months for H3K27M-positive cases, compared to 1 month for those with TERT promoter mutation and 77 months for those harboring neither ( p  = 0.019). Median survival for cases with TP53 mutations was 11.5 months and for those with PPM1D mutations was 84 months. Our findings suggest that high-grade infiltrating gliomas of the spinal cord in adults represent a heterogeneous group of tumors, with variable outcomes possibly related to their molecular profiles.

Disturbances are important for renewal of North American forests. Here we summarize more than 180 site years of eddy covariance measurements of carbon dioxide flux made at forest chronosequences in North America. The disturbances included stand‐replacing fire (Alaska, Arizona, Manitoba, and Saskatchewan) and harvest (British Columbia, Florida, New Brunswick, Oregon, Quebec, Saskatchewan, and Wisconsin) events, insect infestations (gypsy moth, forest tent caterpillar, and mountain pine beetle), Hurricane Wilma, and silvicultural thinning (Arizona, California, and New Brunswick). Net ecosystem production (NEP) showed a carbon loss from all ecosystems following a stand‐replacing disturbance, becoming a carbon sink by 20 years for all ecosystems and by 10 years for most. Maximum carbon losses following disturbance (g C m−2y−1) ranged from 1270 in Florida to 200 in boreal ecosystems. Similarly, for forests less than 100 years old, maximum uptake (g C m−2y−1) was 1180 in Florida mangroves and 210 in boreal ecosystems. More temperate forests had intermediate fluxes. Boreal ecosystems were relatively time invariant after 20 years, whereas western ecosystems tended to increase in carbon gain over time. This was driven mostly by gross photosynthetic production (GPP) because total ecosystem respiration (ER) and heterotrophic respiration were relatively invariant with age. GPP/ER was as low as 0.2 immediately following stand‐replacing disturbance reaching a constant value of 1.2 after 20 years. NEP following insect defoliations and silvicultural thinning showed lesser changes than stand‐replacing events, with decreases in the year of disturbance followed by rapid recovery. NEP decreased in a mangrove ecosystem following Hurricane Wilma because of a decrease in GPP and an increase in ER.

Background. Although pandemic and avian influenza are known to be transmitted via human hands, there are minimal data regarding the effectiveness of routine hand hygiene (HH) protocols against pandemic and avian influenza. Methods. Twenty vaccinated, antibody-positive health care workers had their hands contaminated with 1 mL of 107 tissue culture infectious dose (TCID)>50/0.1 mL live human influenza A virus (H1N1; A/New Caledonia/20/99) before undertaking 1 of 5 HH protocols (no HH [control], soap and water hand washing [SW], or use of 1 of 3 alcohol-based hand rubs [61.5% ethanol gel, 70% ethanol plus 0.5% chlorhexidine solution, or 70% isopropanol plus 0.5% chlorhexidine solution]). H1N1 concentrations were assessed before and after each intervention by viral culture and real-time reverse-transcriptase polymerase chain reaction (PCR). The natural viability of H1N1 on hands for >60 min without HH was also assessed. Results. There was an immediate reduction in culture-detectable and PCR-detectable H1N1 after brief cutaneous air drying—14 of 20 health care workers had H1N1 detected by means of culture (mean reduction, 103–4 TCID>50/0.1 mL), whereas 6 of 20 had no viable H1N1 recovered; all 20 health care workers had similar changes in PCR test results. Marked antiviral efficacy was noted for all 4 HH protocols, on the basis of culture results (14 of 14 had no culturable H1N1; P<.002) and PCR results (P<.001; cycle threshold value range, 33.3–39.4), with SW statistically superior (P<.001) to all 3 alcohol-based hand rubs, although the actual difference was only 1–100 virus copies/µL. There was minimal reduction in H1N1 after 60 min without HH. Conclusions. HH with SW or alcohol-based hand rub is highly effective in reducing influenza A virus on human hands, although SW is the most effective intervention. Appropriate HH may be an important public health initiative to reduce pandemic and avian influenza transmission.

Epidemiological studies have observed that the seasonal peak incidence of influenza virus infection is sometimes separate from the peak incidence of human respiratory syncytial virus (hRSV) infection, with the peak incidence of hRSV infection delayed. This is proposed to be due to viral interference, whereby infection with one virus prevents or delays infection with a different virus. We investigated viral interference between hRSV and 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09) in the ferret model. Infection with A(H1N1)pdm09 prevented subsequent infection with hRSV. Infection with hRSV reduced morbidity attributed to infection with A(H1N1)pdm09 but not infection, even when an increased inoculum dose of hRSV was used. Notably, infection with A(H1N1)pdm09 induced higher levels of proinflammatory cytokines, chemokines, and immune mediators in the ferret than hRSV. Minimal cross-reactive serological responses or interferon γ-expressing cells were induced by either virus ≥14 days after infection. These data indicate that antigen-independent mechanisms may drive viral interference between unrelated respiratory viruses that can limit subsequent infection or disease.

Ultrasonography is one of the key medical imaging modalities for evaluating breast lesions. For differentiating benign from malignant lesions, computer‐aided diagnosis (CAD) systems have greatly assisted radiologists by automatically segmenting and identifying features of lesions. Here, we present deep learning (DL)‐based methods to segment the lesions and then classify benign from malignant, utilizing both B‐mode and strain elastography (SE‐mode) images. We propose a weighted multimodal U‐Net (W‐MM‐U‐Net) model for segmenting lesions where optimum weight is assigned on different imaging modalities using a weighted‐skip connection method to emphasize its importance. We design a multimodal fusion framework (MFF) on cropped B‐mode and SE‐mode ultrasound (US) lesion images to classify benign and malignant lesions. The MFF consists of an integrated feature network (IFN) and a decision network (DN). Unlike other recent fusion methods, the proposed MFF method can simultaneously learn complementary information from convolutional neural networks (CNNs) trained using B‐mode and SE‐mode US images. The features from the CNNs are ensembled using the multimodal EmbraceNet model and DN classifies the images using those features. The experimental results (sensitivity of 100 ± 0.00% and specificity of 94.28 ± 7.00%) on the real‐world clinical data showed that the proposed method outperforms the existing single‐ and multimodal methods. The proposed method predicts seven benign patients as benign three times out of five trials and six malignant patients as malignant five out of five trials. The proposed method would potentially enhance the classification accuracy of radiologists for breast cancer detection in US images.