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Background: The COVID-19 pandemic has significantly impacted global health, with diverse factors influencing the risk of death among reported cases. This study mainly analyzes the main characteristics that have contributed to the increase or decrease in the risk of death among Severe Acute Respiratory Syndrome (SARS) cases classified as COVID-19 reported in southeast Brazil from 2020 to 2023., Methods: This cohort study utilized COVID-19 notification data from the Sistema de Vigilância Epidemiológica (SIVEP) information system in the southeast region of Brazil from 2020 to 2023. Data included demographics, comorbidities, vaccination status, residence area, and survival outcomes. Classical Cox, Cox mixed effects, Prentice, Williams & Peterson (PWP), and PWP fragility models were used to assess the risk of dying over time., Results: Across 987,534 cases, 956,961 hospitalizations, and 330,343 deaths were recorded over the period. Mortality peaked in 2021. The elderly, males, black individuals, lower-educated, and urban residents faced elevated risks. Vaccination reduced death risk by around 20% and 13% in 2021 and 2022, respectively. Hospitalized individuals had lower death risks, while comorbidities increased risks by 20-26%., Conclusion: The study identified demographic and comorbidity factors influencing COVID-19 mortality. Rio de Janeiro exhibited the highest risk, while São Paulo had the lowest. Vaccination significantly reduces death risk. Findings contribute to understanding regional mortality variations and guide public health policies, emphasizing the importance of targeted interventions for vulnerable groups., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Rodrigues et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Obesity is a leading risk factor of pancreatic ductal adenocarcinoma (PDAC) that contributes to poor disease prognosis and outcomes. Retrospective studies have identified this link, but interactions surrounding obesity and PDAC are still unclear. Research has shifted to contributions of fibrosis (desmoplasia) on malignancy, which involves increased deposition of collagens and other extracellular matrix (ECM) molecules and increased ECM crosslinking, all of which contribute to increased tissue stiffening. However, fibrotic stiffening is underrepresented as a model feature in current PDAC models. Fibrosis is shared between PDAC and obesity, and can be leveraged for in vitro model design, as current animal obesity models of PDAC are limited in their ability to isolate individual components of fibrosis to study cell behavior. In the current study, methacrylated type I collagen (PhotoCol ® ) was photo-crosslinked to pathological stiffness levels to recapitulate fibrotic ECM stiffening. PANC-1 cells were encapsulated within PhotoCol ® , and the tumor-tissue constructs were prepared to represent normal (healthy) (~600 Pa) and pathological (~2000 Pa) tissues. Separately, human mesenchymal stem cells were differentiated into adipocytes representing lean (2D differentiation) and obese fat tissue (3D collagen matrix differentiation), and conditioned media was applied to PANC-1 tumor-tissue constructs. Conditioned media from obese adipocytes showed increased vimentin expression, a hallmark of invasiveness and progression, that was not seen after exposure to media from lean adipocytes or control media. Characterization of the obese adipocyte secretome suggested that some PANC-1 differences may arise from increased interleukin-8 and -10 compared to lean adipocytes. Additionally, high matrix stiffness associated induced an amoeboid morphology in PANC-1 cells that was not present at low stiffness. Amoeboid morphology is an accessory to epithelial-to-mesenchymal transition and is used to navigate complex ECM environments. This plasticity has greater implications for treatment efficacy of metastatic cancers. Overall, this work 1) highlights the importance of investigating PDAC-obesity interactions to study the effects on disease progression and persistence, 2) establishes PhotoCol ® as a matrix material that can be leveraged to study amoeboid morphology and invasion in PDAC, and 3) emphasizes the importance of integrating both biophysical and biochemical interactions associated within both pathologies for in vitro PDAC models., Competing Interests: DISCLOSURE STATEMENT The authors declare no conflicts of interest.

We evaluated the bird composition, forest dependence, trophic guilds and avian representativeness associated with 7, 10 and 15 years old reforestations and mature forest patches in order to verify the successional process and avian contribution to the forest restoration. Analyses revealed a segregation of bird composition with a gradual increasing in forest dependent species from 7 years to mature forest. Detrended Correspondence Analysis ranged from those birds often present in semi-open habitats to forest birds, canopy frugivorous and understory insectivorous as the successional stages progressed from the most recent reforestation to the most mature. Although 7 and 10 years of reforestation had the largest composition range, the more generalist, granivorous and forest independent birds, three years were enough to have different bird diversity between them. Avifauna of 15 years patches resembled most closely that of mature forest but still lacked 18 species. In this way, we addressed: 1) planting of herbaceous/shrub and freshy-fruited species in reforestations and; 2) establish riparian forest corridors along the Paraná river to connect these reforestation patches with mature forest. These measures will allow higher avian beta-diversity to maximize the diaspores dispersed by birds to expand and accelerate the rehabilitation of this threatened for forest.

Senescent cells drive age-related tissue dysfunction partially through the induction of a chronic senescence-associated secretory phenotype (SASP) 1 . Mitochondria are major regulators of the SASP; however, the underlying mechanisms have not been elucidated 2 . Mitochondria are often essential for apoptosis, a cell fate distinct from cellular senescence. During apoptosis, widespread mitochondrial outer membrane permeabilization (MOMP) commits a cell to die 3 . Here we find that MOMP occurring in a subset of mitochondria is a feature of cellular senescence. This process, called minority MOMP (miMOMP), requires BAX and BAK macropores enabling the release of mitochondrial DNA (mtDNA) into the cytosol. Cytosolic mtDNA in turn activates the cGAS-STING pathway, a major regulator of the SASP. We find that inhibition of MOMP in vivo decreases inflammatory markers and improves healthspan in aged mice. Our results reveal that apoptosis and senescence are regulated by similar mitochondria-dependent mechanisms and that sublethal mitochondrial apoptotic stress is a major driver of the SASP. We provide proof-of-concept that inhibition of miMOMP-induced inflammation may be a therapeutic route to improve healthspan., (© 2023. The Author(s).)

Pharmacological and genetic studies over the past decade have established the follicle-stimulating hormone (FSH) as an actionable target for diseases affecting millions, namely osteoporosis, obesity, and Alzheimer's disease. Blocking FSH action prevents bone loss, fat gain, and neurodegeneration in mice. We recently developed a first-in-class, humanized, epitope-specific FSH-blocking antibody, MS-Hu6, with a K D of 7.52 nM. Using a Good Laboratory Practice (GLP)-compliant platform, we now report the efficacy of MS-Hu6 in preventing and treating osteoporosis in mice and parameters of acute safety in monkeys. Biodistribution studies using 89 Zr-labeled, biotinylated or unconjugated MS-Hu6 in mice and monkeys showed localization to bone and bone marrow. The MS-Hu6 displayed a β phase t ½ of 7.5 days (180 hr) in humanized Tg32 mice. We tested 217 variations of excipients using the protein thermal shift assay to generate a final formulation that rendered MS-Hu6 stable in solution upon freeze-thaw and at different temperatures, with minimal aggregation, and without self-, cross-, or hydrophobic interactions or appreciable binding to relevant human antigens. The MS-Hu6 showed the same level of "humanness" as human IgG1 in silico and was non-immunogenic in ELISpot assays for IL-2 and IFN-γ in human peripheral blood mononuclear cell cultures. We conclude that MS-Hu6 is efficacious, durable, and manufacturable, and is therefore poised for future human testing., Competing Interests: SG, TK, AG, FK, DS, VD, KS, AP, GP, JM, AT, Mv, TP, JF, JN, FS, ES, SR, PK, LC, JC, AP, SM, HK, MB, PS, KI, VM, RB, CR, AM, SH, MS, MM, JC, MN, VR, SK, JC, NZ, ZF, DL, CR No competing interests declared, JI, TY Reviewing editor, eLife, MZ is an inventor on issued patents on inhibiting FSH for the prevention and treatment of osteoporosis and obesity (U.S. Patent 8,435,948 and 11,034,761). M.Z. is also an inventor on pending patent application on composition and use of humanized monoclonal anti-FSH antibodies, and is co-inventor of a pending patent on the use of FSH as a target for preventing Alzheimer's disease. These patents are owned by Icahn School of Medicine at Mount Sinai (ISMMS), and M.Z. would be recipient of royalties, per institutional policy. M.Z. also consults for several financial platforms, including Gerson Lehman Group and Guidepoint, on drugs for osteoporosis and genetic bone diseases. Deputy editor, eLife, (© 2022, Gera, Kuo, Gumerova et al.)

Assistance dogs are a potential intervention for families of children on the autism spectrum to support participation. However, the lived experience of families with new assistance dogs has not previously been explored. This study described the expectations, benefits, and challenges of assistance dog ownership for families of children on the autism spectrum. Data were collected from four mothers through semi-structured interviews and photovoice prior to assistance dog placement and following 6 months of ownership. Findings indicated assistance dog ownership enhanced the child's self-regulation and socialization, and increased participation in daily routines. Having an assistance dog also enhanced participation in family outings and activities. Challenges included the adjustment period and the lack of public awareness of autism assistance dogs.

Introduction  Light transmission aggregometry (LTA) is regarded as the gold standard in platelet function diagnostics. However, there is a relevant degree of interlaboratory variability in practical applications. Objective  The aim of the present study was to develop a practicable laboratory comparison on LTA and to analyze differences and influencing factors in regard to standardization in five specialized hemostaseological centers. Methods  The study was performed on 30 patients in total. Each center performed LTA on blood samples from six healthy volunteers (three men and three women) using the inductors collagen (Col), adenosine diphosphate (ADP), arachidonic acid (ARA), and ristocetin. The LTA was performed three times using different methods as follows: (1) International Society on Thrombosis and Haemostasis recommendations with identical reagents, (2) in-house protocols and the identical reagents; and (3) in-house protocols and in-house reagents. Results  A total of 396 measurements of 30 probands were performed. Even after standardization of the protocol and using identical reagents, there were significant differences between the centers regarding the final and maximum aggregation ( p  = 0.002 and <0.001) and further significant differences in the maximum and final aggregation according to the wavelength of the device used to measure the LTA (PAP-8: 430 nm, APACT 4004: 740 nm [ p  < 0.001 each]). Using identical reagents but individual inductor concentrations and laboratory protocols also resulted in different maximum and final aggregation. The largest differences were seen with Col and ristocetin; there were significant influences from the reagents' manufacturers in the results of aggregometry for the inductor Col ( p  < 0.01) but not for ADP, ARA, and ristocetin. Conclusion  In this study, we proved that there are significant influences from the used aggregometers, inductors concentrations, and manufacturers. These results illustrate the challenges and importance of standardization of LTA., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Knowledge about cardiac and inflammatory biomarkers in patients with stable coronary artery disease (CAD) is limited. To address this, we analyzed 3072 patients (36% female) with a median follow-up of 10 years in the Leipzig LIFE Heart Study with suspected CAD with coronary angiography. Selected biomarkers included troponin T (hsTNT), N-terminal pro B-type natriuretic peptide (NT-proBNP), copeptin, C-reactive protein (hsCRP), and interleukin-6 (IL-6). Patients were stratified by CAD severity: CAD0 (no sclerosis), CAD1 (non-obstructive, i.e., stenosis < 50%), and CAD2 (≥one stenosis ≥ 50%). Group comparison (GC) included GC1: CAD0 + 1 vs. CAD2; GC2: CAD0 vs. CAD1 + 2. CAD0, CAD1, and CAD2 were apparent in 1271, 631, and 1170 patients, respectively. Adjusted for classical risk factors, hs-cTnT, NT-proBNP, and IL-6 differed significantly in both GC and hsCRP only in GC2. After multivariate analysis, hs-cTnT, NT-proBNP, and IL-6 remained significant in GC1. In GC2, hs-cTnT (p < 0.001) and copeptin (p = 0.014) reached significance. Ten-year survival in groups CAD0, CAD1, and CAD2 was 88.3%, 77.3%, and 72.4%. Incorporation of hs-cTnT, NT-proBNP, copeptin, and IL-6 improved risk prediction (p < 0.001). The studied cardiac and inflammatory biomarkers enable fast and precise non-invasive identification of mortality risk in CAD patients, allowing the tailoring of primary and secondary CAD prevention.

Background: Ameloblastomas are benign odontogenic tumors that can eventually mimic the clinical and radiological features of apical periodontitis. The aim of the present study was to evaluate the clinical, radiological and histological characteristics from a series of ameloblastomas mimicking apical periodontitis diagnosed in a 14-year period., Material and Methods: all cases histologically diagnosed as ameloblastomas from 2005 to 2018 presenting a clinical diagnosis of periapical lesion of endodontic origin were selected for the study. Clinical, radiological and histological characteristics from all cases were tabulated and descriptively and comparatively analyzed., Results: Twenty cases composed the final sample, including 18 solid and 2 unicystic ameloblastomas. Mean age of the affected patients was in the fifth decade with predilection for males (72%). The most common anatomical location was the posterior mandible (55%) and most cases presented a radiolucent unilocular (80%) well-defined (95%) image. Most cases were asymptomatic, but the presence of local swelling and bone cortical rupture were common., Conclusions: Ameloblastomas mimicking periapical lesions of endodontic origin are mostly diagnosed in adult males as well-defined radiolucent unilocular lesions producing local swelling and bone cortical rupture.

Background: Intra-arterial administration of chemotherapy with or without osmotic blood-brain barrier disruption enhances delivery of therapeutic agents to brain tumors. The aim of this study is to evaluate the safety of these procedures., Methods: Retrospectively collected data from a prospective database of consecutive patients with primary and metastatic brain tumors who received intra-arterial chemotherapy without osmotic blood-brain barrier disruption (IA) or intra-arterial chemotherapy with osmotic blood-brain barrier disruption (IA/OBBBD) at Oregon Health and Science University (OHSU) between December 1997 and November 2018 is reported. Chemotherapy-related complications are detailed per Common Terminology Criteria for Adverse Events (CTCAE) guidelines. Procedure-related complications are grouped as major and minor., Results: 4939 procedures (1102 IA; 3837 IA/OBBBD) were performed on 436 patients with various pathologies (primary central nervous system lymphoma [26.4%], glioblastoma [18.1%], and oligodendroglioma [14.7%]). Major procedure-related complications (IA: 12, 1%; IA/OBBBD: 27, 0.7%; P = .292) occurred in 39 procedures including 3 arterial dissections requiring intervention, 21 symptomatic strokes, 3 myocardial infarctions, 6 cervical cord injuries, and 6 deaths within 3 days. Minor procedure-related complications occurred in 330 procedures (IA: 41, 3.7%; IA/OBBBD: 289, 7.5%; P = .001). Chemotherapy-related complications with a CTCAE attribution and grade higher than 3 was seen in 359 (82.3%) patients., Conclusions: We provide safety and tolerability data from the largest cohort of consecutive patients who received IA or IA/OBBBD. Our data demonstrate that IA or IA/OBBBD safely enhance drug delivery to brain tumors and brain around the tumor., (© The Author(s) 2022. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

The edge effect has impacts on seed and seedling survival due to modifications in biotic and abiotic factors. Often, large-seeded tree species lost seed vectors in the forest edge due to the rarity or absence of large frugivores at this habitat type. In this study, I compared the seedling abundance and distribution of the palm Syagrus flexuosa between edges and interiors of three large Cerrado remnants. In every remnant, the number of seedlings around parent palms in the edge was smaller than around palm individuals located in the Cerrado interior. Moreover, the distribution of seedlings around parent palms differed between edges and interiors. In the edges, most seedlings were found under parent crowns, while in the interiors, the contrary occurred. The high concentration of seedlings under parent palms suggests a decrease of seed dispersal at the edges. Because S. flexuosa is a widely distributed palm that serves as an important resource for several animals along Cerrado habitats, changes on the regeneration process of this palm due to edge effects can further impact frugivore populations. Therefore, the decline of seedling establishment along forest edges implies changes in the Cerrado regeneration dynamics, which may compromise the persistence of ecological processes and animal communities.

The COVID-19 pandemic has become a worldwide concern and has motivated the entire scientific community to join efforts to fight it. Studies have shown that SARS-CoV-2 remains viable onsurfaces for days, increasing the chances of human infection. Environmental disinfection is thus an important action to prevent the transmission of the virus. Despite the valuable contribution of the research community to the field of UV-C disinfection by robots, there still lacks a disinfection system that is fully autonomous and computes its trajectory in real-time and in unknown environments. To meet this need, we propose an autonomous UV-C disinfection strategy for indoor environments based on a dynamic Irradiation Map that indicates the amount of energy applied in each region. Our method was tested in different scenarios and compared with other disinfection strategies. Experiments show that our approach delivers better results, especially when targeting high ideal UV-C doses.