Biological Earth observation with animal sensors

Space-based tracking technology using low-cost miniature tags is now delivering data on fine-scale animal movement at near-global scale. Linked with remotely sensed environmental data, this offers a biological lens on habitat integrity and connectivity for conservation and human health; a global network of animal sentinels of environmen-tal change

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

“Zebrafishing” for Novel Genes Relevant to the Glomerular Filtration Barrier

Data for genes relevant to glomerular filtration barrier function or proteinuria is continually increasing in an era of microarrays, genome-wide association studies, and quantitative trait locus analysis. Researchers are limited by published literature searches to select the most relevant genes to investigate. High-throughput cell cultures and other in vitro systems ultimately need to demonstrate proof in an in vivo model. Generating mammalian models for the genes of interest is costly and time intensive, and yields only a small number of test subjects. These models also have many pitfalls such as possible embryonic mortality and failure to generate phenotypes or generate nonkidney specific phenotypes. Here we describe an in vivo zebrafish model as a simple vertebrate screening system to identify genes relevant to glomerular filtration barrier function. Using our technology, we are able to screen entirely novel genes in 4–6 weeks in hundreds of live test subjects at a fraction of the cost of a mammalian model. Our system produces consistent and reliable evidence for gene relevance in glomerular kidney disease; the results then provide merit for further analysis in mammalian models

NOP10 predicts lung cancer prognosis and its associated small nucleolar RNAs drive proliferation and migration

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide underlining the urgent need for new biomarkers and therapeutic targets for this disease. Long noncoding RNAs are critical players in NSCLC but the role of small RNA species is not well understood. In the present study, we investigated the role of H/ACA box small nucleolar RNAs (snoRNAs) and snoRNA-bound ribonucleoproteins (snoRNPs) in the tumorigenesis of NSCLC. H/ACA box snoRNPs including the NOP10 core protein were highly expressed in NSCLC. High levels of either NOP10 mRNA or protein were associated with poor prognosis in NSCLC patients. Loss of NOP10 and subsequent reduction of H/ACA box snoRNAs and rRNA pseudouridylation inhibited lung cancer cell growth, colony formation, migration, and invasion. A focused CRISPR/Cas9 snoRNA knockout screen revealed that genomic deletion of SNORA65, SNORA7A, and SNORA7B reduced proliferation of lung cancer cells. In line, high levels of SNORA65, SNORA7A, and SNORA7B were observed in primary lung cancer specimens with associated changes in rRNA pseudouridylation. Knockdown of either SNORA65 or SNORA7A/B inhibited growth and colony formation of NSCLC cell lines. Our data indicate that specific H/ACA box snoRNAs and snoRNA-associated proteins such as NOP10 have an oncogenic role in NSCLC providing new potential biomarkers and therapeutic targets for the disease

Endovascular versus medical therapy in posterior cerebral artery stroke: role of baseline NIHSS and occlusion site.

Background: Acute ischemic stroke (AIS) with isolated posterior cerebral artery occlusion (iPCAO) lacks management evidence from randomized trials. We aimed to evaluate whether the association between endovascular treatment (EVT) and outcomes in iPCAO-AIS is modified by initial stroke severity (baseline NIHSS) and arterial occlusion site. Methods: Based on the multicenter, retrospective, case-control study of consecutive iPCAO-AIS patients (PLATO study), we assessed the heterogeneity of EVT outcomes compared to medical management (MM) for iPCAO, according to baseline NIHSS (≤6 vs. >6) and occlusion site (P1 vs. P2), using multivariable regression modelling with interaction terms. The primary outcome was the favorable shift of 3-month mRS. Secondary outcomes included excellent outcome (mRS 0-1), functional independence (mRS 0-2), symptomatic intracranial hemorrhage (sICH) and mortality. Results: From 1344 patients assessed for eligibility, 1,059 were included (median age 74 years, 43.7% women, 41.3% had intravenous thrombolysis), 364 receiving EVT and 695 MM. Baseline stroke severity did not modify the association of EVT with 3-month mRS distribution (pint=0.312), but did with functional independence (pint=0.010), with a similar trend on excellent outcome (pint=0.069). EVT was associated with more favorable outcomes than MM in patients with baseline NIHSS>6 (mRS 0-1: 30.6% vs. 17.7%, aOR=2.01, 95%CI=1.22-3.31; mRS 0-2: 46.1% vs. 31.9%, aOR=1.64, 95%CI=1.08-2.51), but not in those with NIHSS≤6 (mRS 0-1: 43.8% vs. 46.3%, aOR=0.90, 95%CI=0.49-1.64; mRS 0-2: 65.3% vs. 74.3%, aOR=0.55, 95%CI=0.30-1.0). EVT was associated with more sICH regardless of baseline NIHSS (pint=0.467), while the mortality increase was more pronounced in patients with NIHSS≤6 (pint=0.044, NIHSS≤6: aOR=7.95,95%CI=3.11-20.28, NIHSS>6: aOR=1.98,95%CI=1.08-3.65). Arterial occlusion site did not modify the association of EVT with outcomes compared to MM. Conclusion: Baseline clinical stroke severity, rather than the occlusion site, may be an important modifier of the association between EVT and outcomes in iPCAO. Only severely affected patients with iPCAO (NIHSS>6) had more favorable disability outcomes with EVT than MM, despite increased mortality and sICH

Safety and efficacy of immunotherapy with the recombinant B-cell epitope-based grass pollen vaccine BM32

textabstractBackground: BM32 is a grass pollen allergy vaccine based on recombinant fusion proteins consisting of nonallergenic peptides from the IgE-binding sites of the 4 major grass pollen allergens and the hepatitis B preS protein. Objective: We sought to study the safety and clinical efficacy of immunotherapy (allergen immunotherapy) with BM32 in patients with grass pollen-induced rhinitis and controlled asthma. Methods: A double-blind, placebo-controlled, multicenter allergen immunotherapy field study was conducted for 2 grass pollen seasons. After a baseline season, subjects (n = 181) were randomized and received 3 preseasonal injections of either placebo (n = 58) or a low dose (80 μg, n = 60) or high dose (160 μg, n = 63) of BM32 in year 1, respectively, followed by a booster injection in autumn. In the second year, all actively treated subjects received 3 preseasonal injections of the BM32 low dose, and placebo-treated subjects continued with placebo. Clinical efficacy was assessed by using combined symptom medication scores, visual analog scales, Rhinoconjunctivitis Quality of Life Questionnaires, and asthma symptom scores. Adverse events were graded according to the European Academy of Allergy and Clinical Immunology. Allergen-specific antibodies were determined by using ELISA, ImmunoCAP, and ImmunoCAP ISAC. Results: Although statistical significance regarding the primary end point was not reached, BM32-treated subjects, when compared with placebo-treated subjects, showed an improvement regarding symptom medication, visual analog scale, Rhinoconjunctivitis Quality of Life Questionnaire, and asthma symptom scores in both treatment years. This was accompanied by an induction of allergen-specific IgG without induction of allergen-specific IgE and a reduction in the seasonally induced increase in allergen-specific IgE levels in year 2. In the first year, more grade 2 reactions were observed in the active (n = 6) versus placebo (n = 1) groups, whereas there was almost no difference in the second year. Conclusions: Injections of BM32 induced allergen-specific IgG, improved clinical symptoms of seasonal grass pollen allergy, and were well tolerated