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In the backdrop of the global obesity pandemic, recognized as a notable risk factor for coronavirus disease 2019 (COVID-19) complications, the study aims to explore clinical and epidemiological attributes of hospitalized COVID-19 patients throughout 2021 in Brazil. Focused on four distinct age cohorts, the investigation scrutinizes parameters such as intensive care unit (ICU) admission frequency, invasive mechanical ventilation (IMV) usage, and in-hospital mortality among individuals with and without obesity. Using a comprehensive cross-sectional study methodology, encompassing adult COVID-19 cases, data sourced from the Influenza Epidemiological Surveillance Information System comprises 329 206 hospitalized patients. Of these individuals, 26.3% were affected by obesity. Analysis reveals elevated rates of ICU admissions, increased dependence on IMV, and heightened in-hospital mortality among the individuals with obesity across all age groups (p < .001). Logistic regression, adjusting for confounding variables, underscores a progressively rising odds ratio for mortality in younger age brackets: 1.2 (95%CI 1.1-1.3) for those under 50 years, 1.1 (95%CI 1.0-1.2) for the 50-59 age group, and 1.1 (95%CI 1.0-1.2) for the 60-69 age group. Conversely, no significant mortality difference is observed for patients over 70 years (OR: 0.972, 95%CI 0.9-1.1). In summary, hospitalized COVID-19 patients with obesity, particularly in younger age groups, exhibit elevated rates of ICU admission, IMV requirement, and in-hospital mortality compared with the control group. Notably, the 'obesity paradox' is not evident among hospitalized COVID-19 patients in 2021., (© 2024 World Obesity Federation.)

Introduction: Cancer has become a public health problem worldwide, affecting individuals of different age groups, including children, young adults and older patients., Objective: To determine the clinical profile, staging and standard of oncological treatment of the 10 most frequent primary sites of cancer in young patients (< 60 years) vs older patients (≥ 60 years old) diagnosed between 2000 and 2019 in Brazil., Materials and Methods: This cross-sectional study used data from the secondary database of the Hospital Cancer Registry, available on the web www.inca.org.br. Patients with cancer who were older than 18 years were included. Patients with non-melanoma skin cancer and with incomplete data on primary site and staging were excluded., Results: The database had data from 1,891,912 eligible patients, of which 1,461,080 (77.2 %) corresponded to the ten leading cancer types which were to be evaluated in this study. Cancers of the breast, prostate, cervix, lung, colon, stomach, rectum, oesophagus, thyroid and larynx were the 10 most frequent cancer types identified. The mean of age of patients was 58.8 ± 14.2 years and most of them were female (59.8 %). Those in the older group were more commonly reported (50.8 %) and this group included more former or current smokers (48.4 % vs 40.8 %, p < 0.001). Young patients received more all-oncological treatment: surgery (53.2 % vs 41.1 %, p < 0.001), radiotherapy (47.3 % vs 46.3 %, p < 0.001) and chemotherapy (53.6 % vs 39.3 %, p < 0.001) than older patients., Conclusion: Evaluating cancer patients by age group may enhance cancer surveillance, redirecting control strategies and prioritising patients with more common primary site types., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest regarding this subject., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Background: Cancer immunotherapy has had an important role in oncologic therapeutics for patients with non-small cell lung cancer (NSCLC) using checkpoint inhibitors. We will explore the possible prognosis biomarker candidates such as: soluble OX40 (sOX40), OX40L (sOX40L), Glucocorticoid-induced tumor necrosis factor receptor family-related receptor (GITR), and their ligand (GITRL), 4-1BB or tumor necrosis factor receptor superfamily 9 (TNFRS9) and inducible T cell co-stimulator (ICOS) in peripheral blood of NSCLC patients., Methods: Fifty-eight patients were diagnosed with advanced NSCLC between January 2019 and March 2020., Results: High sOX40 and low s4-1BB levels in smokers compared non-smoker NSCLC patients. Lower sOX40L levels were found in the male than female (p < 0.05). High sOX40 and sGITRL in stage III compared to the stage IV (p < 0.05). With follow-up at 21.4 months, 44.1% and 91.1% were alive in the sGITR high and sGITR low groups, respectively (p = 0.02), and 73.3% and 27.7% were alive in the sGITRL high and sGITRL low groups, respectively (p = 0.02). At 22 months, 38.7% and 92.3% were alive in the sOX40L high and sOX40L low groups, respectively (p = 0.01)., Conclusion: sGITR, sGITRL, and sOX40L levels were potential prognostic biomarkers and could have an important role as new targets of immunotherapy in NSCLC patients. sGITR, sGITRL, sOX40L, and sOX40 levels were associated with smoking, sex, stage, and age in NSCLC., (© 2024 Wiley Periodicals LLC.)

Background: The immune system is recognized to have therapeutic potential to destroy cancer cells. Soluble T-cell immunoglobulin mucin domain-3 (sTIM-3) and its ligand galectin 9 (Gal-9) cause suppression of cytokine production, cell cycle arrest and cell death. sTIM-3 and Gal-9 levels may have prognostic implications in non-small-cell lung cancer (NSCLC) patients., Methods: This prospective cohort study was performed at Instituto de Medicina Integral Prof. Fernando Figueira, Recife, Pernambuco, Brazil. Fifty-eight patients were diagnosed with advanced NSCLC from January 2019 to January 2020., Results: The age median was of 64.0 years. Soluble galectin-9 (sGal-9) levels in the smokers compared to nonsmoker patients (p < 0.0001). By using the receiver operating characteristic curve, we found that a baseline of 1694 pg/mL (cutoff). sGAL9 with specificity (72.2%), sensitivity (83.2%) and area under the curve = 0.8497 (p < 0.0004). Until 18.2 months, 46.8% and 72.9% were alive in the sGAL9 low and sGAL9 high groups, respectively (log-rank test; p = 0.02). The median survival was 15.9 months for sGAL9 low (≤1694 pg/mL)., Conclusion: This study indicated an association of tobacco with the release of circulating sGal-9 levels and the accuracy of sGal-9 as a potential biomarker predictive of survival time in advanced NSCLC patients. Furthermore, sGal-9 has may be a potential therapeutic target in the advanced NSCLC., (© 2024 Wiley Periodicals LLC.)

9H- and 7H-2,6-Diaminopurine (26DAP) photoinduced events in vacuum were studied at the MS-CASPT2/cc-pVDZ level of theory. The S 1 1 (ππ* L a ) state is initially populated evolving barrierless towards its minimum energy structure, from where two photochemical events can take place in both tautomers. The first is the return of the electronic population to the ground state via the C6 conical intersection (CI-C6). The second involves an internal conversion to the ground through the C2 conical intersection (CI-C2). According to our geodesic interpolated paths connecting the critical structures, the second route is less favorable in both tautomers, due to the presence of high energy barriers. Our calculations suggest a competition between fluorescence and ultrafast relaxation to the electronic ground state via internal conversion process. Based on our calculated potential energy surfaces and experimental excited state lifetimes from the literature, we can infer that the 7H- must have a greater fluorescence yield than the 9H-tautomer. We also explored the triplet state population mechanisms on the 7H-26DAP to understand their long-lived components observed experimentally., (© 2023 American Society for Photobiology.)

The epiretinal membrane is a fibrocontractile tissue that forms on the inner surface of the retina, causing visual impairment ranging from mild to severe, and even retinal detachment. Müller glial cells actively participate in the formation of this membrane. Current research is constantly seeking for new therapeutic approaches that aim to prevent or treat cellular dysfunctions involved in the progression of this common fibrosis condition. The Rho GTPases signaling pathway regulates several processes associated with the epiretinal membrane, such as cell proliferation, migration, and contraction. Rho kinase (ROCK), an effector of the RhoA GTPase, is an interesting potential therapeutic target. This study aimed to evaluate the effects of a ROCK inhibitor (Y27632) on human Müller cells viability, growth, cytoskeletal organization, expression of extracellular matrix components, myofibroblast differentiation, migration, and contractility. Müller cells of the MIO-M1 lineage were cultured and treated for different periods with the inhibitor. Viability was evaluated by MTT assay and trypan blue exclusion method, and growth was evaluated by growth curve and BrdU incorporation assay. The actin cytoskeleton was stained with fluorescent phalloidin, intermediate filaments and microtubules were analyzed with immunofluorescence for vimentin and α-tubulin. Gene and protein expression of collagens I and V, laminin and fibronectin were evaluated by rt-PCR and immunofluorescence. Chemotactic and spontaneous cell migration were studied by transwell assay and time-lapse observation of live cells, respectively. Cell contractility was assessed by collagen gel contraction assay. The results showed that ROCK inhibition by Y27632 did not affect cell viability, but decreased cell growth and proliferation after 72 h. There was a change in cell morphology and organization of F-actin, with a reduction in the cell body, disappearance of stress fibers and formation of long, branched cell extensions. Microtubules and vimentin filaments were also affected, possibly because of F-actin alterations. The inhibitor also reduced gene expression and immunoreactivity of smooth muscle α-actin, a marker of myofibroblasts. The expression of extracellular matrix components was not affected by the inhibitor. Chemotactic cell migration showed no significant changes, while cell contractility was substantially reduced. No spontaneous migration of MIO-M1 cells was observed. In conclusion, pharmacological inhibition of ROCK in Müller cells could be a potentially promising approach to treat epiretinal membranes by preventing cell proliferation, contractility and transdifferentiation, without affecting cell viability., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Unspecific peroxygenases (UPOs) are emerging as promising biocatalysts for selective oxyfunctionalization of unactivated C-H bonds. However, their potential in large-scale synthesis is currently constrained by suboptimal chemical selectivity. Improving the selectivity of UPOs requires a deep understanding of the molecular basis of their catalysis. Recent molecular simulations have sought to unravel UPO's selectivity and inform their design principles. However, most of these studies focused on substrate-binding poses. Few researchers have investigated how the reactivity of CpdI, the principal oxidizing intermediate in the catalytic cycle, influences selectivity in a realistic protein environment. Moreover, the influence of protein electrostatics on the reaction kinetics of CpdI has also been largely overlooked. To bridge this gap, we used multiscale simulations to interpret the regio- and enantioselective hydroxylation of the n -heptane substrate catalyzed by Agrocybe aegerita UPO ( Aae UPO). We comprehensively characterized the energetics and kinetics of the hydrogen atom-transfer (HAT) step, initiated by CpdI, and the subsequent oxygen rebound step forming the product. Notably, our approach involved both free energy and potential energy evaluations in a quantum mechanics/molecular mechanics (QM/MM) setting, mitigating the dependence of results on the choice of initial conditions. These calculations illuminate the thermodynamics and kinetics of the HAT and oxygen rebound steps. Our findings highlight that both the conformational selection and the distinct chemical reactivity of different substrate hydrogen atoms together dictate the regio- and enantio-selectivity. Building on our previous study of CpdI's formation in Aae UPO, our results indicate that the HAT step is the rate-limiting step in the overall catalytic cycle. The subsequent oxygen rebound step is swift and retains the selectivity determined by the HAT step. We also pinpointed several polar and charged amino acid residues whose electrostatic potentials considerably influence the reaction barrier of the HAT step. Notably, the Glu196 residue is pivotal for both the CpdI's formation and participation in the HAT step. Our research offers in-depth insights into the catalytic cycle of Aae UPO, which will be instrumental in the rational design of UPOs with enhanced properties.

Unspecific peroxygenases (UPOs) can selectively oxyfunctionalize unactivated hydrocarbons by using peroxides under mild conditions. They circumvent the oxygen dilemma faced by cytochrome P450s and exhibit greater stability than the latter. As such, they hold great potential for industrial applications. A thorough understanding of their catalysis is needed to improve their catalytic performance. However, it remains elusive how UPOs effectively convert peroxide to Compound I (CpdI), the principal oxidizing intermediate in the catalytic cycle. Previous computational studies of this process primarily focused on heme peroxidases and P450s, which have significant differences in the active site from UPOs. Additionally, the roles of peroxide unbinding in the kinetics of CpdI formation, which is essential for interpreting existing experiments, have been understudied. Moreover, there has been a lack of free energy characterizations with explicit sampling of protein and hydration dynamics, which is critical for understanding the thermodynamics of the proton transport (PT) events involved in CpdI formation. To bridge these gaps, we employed multiscale simulations to comprehensively characterize the CpdI formation in wild-type UPO from Agrocybe aegerita ( Aae UPO). Extensive free energy and potential energy calculations were performed in a quantum mechanics/molecular mechanics setting. Our results indicate that substrate-binding dehydrates the active site, impeding the PT from H 2 O 2 to a nearby catalytic base (Glu196). Furthermore, the PT is coupled with considerable hydrogen bond network rearrangements near the active site, facilitating subsequent O-O bond cleavage. Finally, large unbinding free energy barriers kinetically stabilize H 2 O 2 at the active site. These findings reveal a delicate balance among PT, hydration dynamics, hydrogen bond rearrangement, and cosubstrate unbinding, which collectively enable efficient CpdI formation. Our simulation results are consistent with kinetic measurements and offer new insights into the CpdI formation mechanism at atomic-level details, which can potentially aid the design of next-generation biocatalysts for sustainable chemical transformations of feedstocks.

Molecular photoswitches offer precise, reversible photocontrol over biomolecular functions and are promising light-regulated drug candidates with minimal side effects. Quantifying thermal isomerization rates of photoswitches in their target biomolecules is essential for fine-tuning their light-controlled drug activity. However, the effects of protein binding on isomerization kinetics remain poorly understood, and simulations are crucial for filling this gap. Challenges in the simulation include describing multireference electronic structures near transition states, disentangling competing reaction pathways, and sampling protein-ligand interactions. To overcome these challenges, we used multiscale simulations to characterize the thermal isomerization of photostatins (PSTs), which are light-regulated microtubule inhibitors for potential cancer phototherapy. We employed a new ab initio multireference electronic structure method in a quantum mechanics/molecular mechanics setting and combined it with enhanced sampling techniques to characterize the cis to trans free-energy profiles of three PSTs in a vacuum, aqueous solution, and tubulin dimer. The significant advantage of our novel approach is the efficient treatment of the multireference character in PSTs' electronic wavefunction throughout the conformational sampling of protein-ligand interactions along their isomerization pathways. We also benchmarked our calculations using high-level ab initio multireference electronic structure methods and explored the competing isomerization pathways. Notably, calculations in a vacuum and implicit solvent models cannot predict the order of the PSTs' thermal half-lives in the aqueous solution observed in the experiment. Only by explicitly treating the solvent molecules can the correct order of isomerization kinetics be reproduced. Protein binding perturbs free-energy barriers due to hydrogen bonding between PSTs and nearby polar residues. Our work generates comprehensive, high-quality benchmark data and offers guidance for selecting computational methods to study the thermal isomerization of photoswitches. Ab initio multireference free-energy calculations in explicit molecular environments are crucial for predicting the effects of substituents on the thermal half-lives of photoswitches in biological systems.

Objective: To determine the clinical profile of COVID-19 inpatients who were vaccinated prior to hospitalization and to compare the risk factors for death and the 28-day survival rate of between those inpatients vaccinated with one, two, or three doses and unvaccinated COVID-19 inpatients., Methods: This was a retrospective observational cohort study involving COVID-19 patients admitted to a referral hospital in the city of Recife, Brazil, between July of 2020 and June of 2022., Results: The sample comprised 1,921 inpatients, 996 of whom (50.8%) were vaccinated prior to hospitalization. After adjusting the mortality risk for vaccinated patients, those undergoing invasive mechanical ventilation (IMV) had the highest mortality risk (adjusted OR [aOR] = 7.4; 95% CI, 3.8-14.1; p < 0.001), followed by patients > 80 years of age (aOR = 7.3; 95% CI, 3.4-15.4; p < 0.001), and those needing vasopressors (aOR = 5.6; 95% CI, 2.9-10.9; p < 0.001). After adjusting the mortality risk for all patients, having received three vaccine doses (aOR = 0.06; 95% CI, 0.03-0.11; p < 0.001) was the most important protective factor against death. There were progressive benefits of vaccination, reducing the frequency of ICU admissions, use for IMV, and death (respectively, from 44.9%, 39.0% and 39.9% after the first dose to 16.7%, 6.2% and 4.4% after the third dose), as well as significant improvements in survival after each subsequent dose (p < 0.001)., Conclusions: Vaccines were effective in reducing illness severity and death in this cohort of COVID-19 inpatients, and the administration of additional doses conferred them with accumulative vaccine protection.

Introduction: To determine the incidence, morbidity, and mortality rate of laryngeal cancer in two decades and its epidemiological, clinical, and histological characteristics by sex in Brazil., Methods: This ecological study used three reliable sources of secondary data: population- and hospital-based cancer registries and the national mortality database. All data available from 2000 to 2019 were considered., Results: The incidence of male laryngeal cancer decreased from 9.20 to 4.95 per 100,000 from 2000 to 2018, while mortality slightly decreased from 3.37 to 3.30 per 100,000 from 2000 to 2019. In the same period, the female incidence decreased from 1.26 to 0.48 per 100,000; however, mortality slightly increased from 0.34 to 0.36 per 100,000. Of 221,566 individuals with head and neck cancer, 27 % presented laryngeal cancer. The median age was 61 years (54-69), and most individuals were male (86.6 %), smokers (66.2 %), diagnosed with locally advanced cancer (66.7 %), and squamous cell carcinoma as the main histological type (93.2 %). Male tended to be older (p < 0.001), white (p < 0.001), smokers (p < 0.001), and present late treatment initiation (p < 0.001) and early death (p < 0.001) compared with female., Conclusion: The male laryngeal cancer affected mainly at productive age but with a decreased incidence, probably due to a reduction in smoking habit. However, mortality did not change, which may be explained by the late diagnosis and lack of access to radiotherapy., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest regarding this subject., (Copyright © 2023. Published by Elsevier Ltd.)

The guanine derivative, 5-aza-7-deazaguanine ( 5N7C G) has recently been proposed as one of four unnatural bases, termed Hachimoji (8-letter) to expand the genetic code. We apply steady-state and time-resolved spectroscopy to investigate its electronic relaxation mechanism and probe the effect of atom substitution on the relaxation mechanism in polar protic and polar aprotic solvents. Mapping of the excited state potential energy surfaces is performed, from which the critical points are optimized by using the state-of-art extended multi-state complete active space second-order perturbation theory. It is demonstrated that excitation to the lowest energy 1 ππ* state of 5N7C G results in complex dynamics leading to ca. 10- to 30-fold slower relaxation (depending on solvent) compared with guanine. A significant conformational change occurs at the S 1 minimum, resulting in a 10-fold greater fluorescence quantum yield compared with guanine. The fluorescence quantum yield and S 1 decay lifetime increase going from water to acetonitrile to propanol. The solvent-dependent results are supported by the quantum chemical calculations showing an increase in the energy barrier between the S 1 minimum and the S 1 /S 0 conical intersection going from water to propanol. The longer lifetimes might make 5N7C G more photochemically active to adjacent nucleobases than guanine or other nucleobases within DNA., (© 2022 The Authors. Photochemistry and Photobiology published by Wiley Periodicals LLC on behalf of American Society for Photobiology.)

Divergence in acoustic signals may have a crucial role in the speciation process of animals that rely on sound for intra-specific recognition and mate attraction. The acoustic adaptation hypothesis (AAH) postulates that signals should diverge according to the physical properties of the signalling environment. To be efficient, signals should maximize transmission and decrease degradation. To test which drivers of divergence exert the most influence in a speciose group of insects, we used a phylogenetic approach to the evolution of acoustic signals in the cicada genus Tettigettalna, investigating the relationship between acoustic traits (and their mode of evolution) and body size, climate and micro-/macro-habitat usage. Different traits showed different evolutionary paths. While acoustic divergence was generally independent of phylogenetic history, some temporal variables' divergence was associated with genetic drift. We found support for ecological adaptation at the temporal but not the spectral level. Temporal patterns are correlated with micro- and macro-habitat usage and temperature stochasticity in ways that run against the AAH predictions, degrading signals more easily. These traits are likely to have evolved as an anti-predator strategy in conspicuous environments and low-density populations. Our results support a role of ecological selection, not excluding a likely role of sexual selection in the evolution of Tettigettalna calling songs, which should be further investigated in an integrative approach., (© 2022 The Authors. Journal of Evolutionary Biology published by John Wiley & Sons Ltd on behalf of European Society for Evolutionary Biology.)

Idiopathic epiretinal membrane (iERM) is a fibrocellular proliferation on the inner surface of the retina, which leads to decreased visual acuity and even central visual loss. As iERM is associated to advanced age and posterior vitreous detachment, a higher prevalence is expected with increasing life expectancy and aging of the global population. Although various cell types of retinal and extra-retinal origin have been described in iERMs (Müller glial cells, astrocytes, hyalocytes, retinal pigment epithelium cells, myofibroblasts, and fibroblasts), myofibroblasts have a central role in collagen production and contractile activity. Thus, myofibroblast differentiation is considered a key event for the iERM formation and progression, and fibroblasts, Müller glial cells, hyalocytes, and retinal pigment epithelium have been identified as myofibroblast precursors. On the other side, the different cell types synthesize growth factors, cytokines, and extracellular matrix, which have a crucial role in ERM pathogenesis. In the present review, the major cellular components and their functions are summarized, and their possible roles in the iERM formation are discussed. By exploring in detail the cellular and molecular aspects of iERM, we seek to contribute for better understanding of this fibrotic disease and the origin of myofibroblasts, which may eventually drive to more targeted therapeutic approaches., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Patients with cancer need to receive their proper treatment and often cannot wait for their treatment, despite delays due to the COVID-19 pandemic. As a result, many cancer centers have had challenges maintaining their oncological activities., Objectives: To compare the average hospital management data and indicators in two different periods, with and without the peak of COVID-19 cases, from an important tertiary cancer center in the northeast region of Brazil., Methods: A retrospective and observational study was performed comparing average hospital administrative data and indicators, between January to March v April to June, 2020 exclusively at the Hospital de Câncer de Pernambuco, Brazil., Results: There were on average a 13% reduction in the chemotherapy administered (P = .131), 17% fewer radiotherapy treatments carried out (P = .043) and 41% as many oncologic surgeries undertaken (P = .002). There was a reduction in the number of sessions of out-patient chemotherapy of 8•6% (P = .271) and chemotherapy inpatients of 33% (P = .038). Admission of new cases of patients with cancer was reduced by 44% (P = .007) during the period analyzed. Ambulatory appointments also decreased by 55% (P = .004) and emergency room appointments fell by 7•9% (P = .495). The number of hospitalizations was reduced by 36% (P = .005) and the occupancy rate decreased by 23•6% (P = .003), while the length of individual hospital stays (in days) increased 10•5% (P = .116)., Conclusion: We report a reduction in the number of radiotherapy treatments and surgeries performed cancer carried out, ambulatory and emergency appointments, hospitalization and admission of new cases of cancer during peak of COVID-19 in an important public tertiary cancer center in the northeast region of Brazil., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Coronavirus disease 2019 (COVID-19) and cancer are serious public health problems worldwide. However, little is known about the risk factors of in-hospital mortality among COVID-19 patients with and without cancer in Brazil. The objective of this study was to evaluate the risk factors of in-hospital mortality among COVID-19 patients with and without cancer and to compare mortality according to gender and topography during the year 2020 in Brazil., Methods: This was a secondary data study of hospitalized adult patients with a diagnosis of COVID-19 by real-time polymerase chain reaction testing in Brazil. The data were collected from the Influenza Epidemiological Surveillance Information System., Results: This study analyzed data from 322,817 patients. The prevalence of cancer in patients with COVID-19 was 2.3%. COVID-19 patients with neurological diseases and cancer had the most lethal comorbidities in both sexes. COVID-19 patients with cancer were more likely to be older (median age, 67 vs 62 years; P < .001), to have a longer hospital stay (13.1 vs 11.5 days; P < .001), to be admitted to the intensive care unit (45.3% vs 39.6%; P < .001), to receive more invasive mechanical ventilation (27.1% vs 21.9%), and to have a higher risk of death (adjusted odds ratio [aOR], 1.94; 95% confidence interval [CI], 1.83-2.06; P < .001) than those without cancer. Patients with hematological neoplasia (aOR, 2.85; 95% CI, 2.41-3.38; P < .001) had a higher risk of mortality than those with solid tumors (aOR, 1.83; 95% CI, 1.72-1.95; P < .001) in both sexes., Conclusions: Brazilian COVID-19 patients with cancer have higher disease severity and a higher risk of mortality than those without cancer., (© 2021 American Cancer Society.)

Background: Lung cancer is the principal cause of cancer-related deaths worldwide; however, there has been controversy as to whether there is a difference in survival rate according to gender in Brazil. The aim of the present study, therefore, was to compare the epidemiologic and clinical profile and the overall survival of patients with lung cancer according to gender., Patients and Methods: A retrospective cohort study was performed involving 1283 patients diagnosed with lung cancer between 2006 and 2014 at a single cancer center. Survival analysis was conducted using Kaplan-Meier statistics. A log-rank test was used to assess differences between survival curves, and Cox proportional hazards regression analysis was performed to quantitate the relationship between gender and overall survival., Results: Compared with men, women were more frequently younger (P < .001), nonsmokers (P = .007), diagnosed with adenocarcinoma (P < .001), had early stage disease (P < .001), received surgery or surgery in combination with chemotherapy (P < .001), and had a better survival rate (P < .001). The median overall survival rate was higher in women (14.2 vs. 10.5 months in men; P < .001). Cox regression-adjusted analysis shows that women were 16% less likely to die than men (hazard ratio, 0.84; 95% confidence interval, 0.72-0.98; P = .03)., Conclusions: A higher overall survival rate was found in women with lung cancer as compared with men with lung cancer in Brazil., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aim: The aim of this study was to evaluate the frequency and median time for the development of metastases and prognosis by metastatic site after the diagnosis of non-small-cell lung cancer (NSCLC). Patients & methods: This cohort study was conducted with 1096 patients diagnosed with NSCLC between 2006 and 2014. Results: The most prevalent site of NSCLC metastases was the respiratory system. The nervous and adrenal systems presented the longest median time for the development of metastases. The 6-month survival varied from 68.2% for liver to 79.9% for the nervous system. Bone metastases were associated with a higher risk of death. Conclusion: The respiratory system was the most prevalent site of metastases. OS and risk of death varied according to the metastatic site.

Vitreous alterations occur from early stages and continue through the normal aging, with gradual lamellae formation and the appearance of liquefied spaces, which eventually leads to complications, such as retinal tear, retinal detachment, and intravitreal hemorrhage. The aim of the present study was to investigate the expression of let-7 miRNA family in the vitreous and retina in newborn (1-3- day-old), young adult (2-month-old), and aging (12-month-old) rats, as well as their role as regulators of vitreous components. MicroRNAs are small, non-coding RNAs that post-transcriptionally regulate gene expression. Our results showed detection of all investigated let-7 isoforms (let-7a, let-7b, let-7c, let-7d, let-7e, let-7f and let-7i) in the retina and vitreous. Although most let-7 members were significantly upregulated in the vitreous during development, only let-7b, let-7c, and let-7e followed this same expression pattern in the retina. Let-7b and -7c increased in aging vitreous as well, and were expressed in vitro by Müller glial cells and their extracellular vesicles. Moreover, let-7 targeted hyaluronan synthase 2 (Has2) mRNA, a synthesizing enzyme of hyaluronan. These observations indicate that let-7 function is important during retina and vitreous development, and that isoforms of let-7 increased with aging, potentially modulating hyaluronan content., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To characterize the clinical and histological profile, as well as treatment patterns, of patients with early-stage, locally advanced (LA), or advanced/metastatic (AM) lung cancer, diagnosed between 2000 and 2014, in Brazil., Methods: This was an analytical cross-sectional epidemiological study employing data obtained for the 2000-2014 period from the hospital cancer registries of two institutions in Brazil: the José Alencar Gomes da Silva National Cancer Institute, in the city of Rio de Janeiro; and the São Paulo Cancer Center Foundation, in the city of São Paulo., Results: We reviewed the data related to 73,167 patients with lung cancer. The proportions of patients with early-stage, LA, and AM lung cancer were 13.3%, 33.2%, and 53.4%, respectively. The patients with early-stage lung cancer were older and were most likely to receive a histological diagnosis of adenocarcinoma; the proportion of patients with early-stage lung cancer remained stable throughout the study period. In those with LA lung cancer, squamous cell carcinoma predominated, and the proportion of patients with LA lung cancer decreased significantly over the period analyzed. Those with AM lung cancer were younger and were most likely to have adenocarcinoma; the proportion of patients with AM lung cancer increased significantly during the study period. Small cell carcinoma accounted for 9.2% of all cases. In our patient sample, the main treatment modality was chemotherapy., Conclusions: It is noteworthy that the frequency of AM lung cancer increased significantly during the study period, whereas that of LA lung cancer decreased significantly and that of early-stage lung cancer remained stable. Cancer treatment patterns, by stage, were in accordance with international guidelines.

Introduction: Lung cancer is the principal cause of death from cancer worldwide. However, little is known of its epidemiological and histological profile and of the incidence and mortality rates in Brazil according to sex., Objectives: To evaluate the incidence, morbidity and mortality rates of lung cancer in Brazil from 2000 to 2014, as well as the epidemiological, clinical and morphological profile of women with lung cancer in Brazil is described., Methods: An ecological study was conducted using three reliable sources of secondary data: population-based cancer registries, hospital-based cancer registries and the national mortality database., Results: The incidence rate in women increased from 7.92/100,000 in 2000 to 9.12/100,000 in 2012, while mortality increased from 6.02/100,000 in 2000 to 8.29/100,000 in 2014. In men, the incidence decreased from 23.40/100,000 in 2000 to 18.47/100,000 in 2012 and mortality also fell from 16.12/100,000 to 15.11/100,000 in 2014. There was a reduction in the male-to-female ratio from 2.54 in 2000 to 1.46 in 2014. Women tended to be younger (p < 0.001), black (p < 0.001), non-smokers (p < 0.001), to have adenocarcinoma or small-cell lung cancer (p < 0.001), and to have metastatic disease (p < 0.001). In addition, the time between diagnosis and the start of cancer treatment was longer in women (p < 0.001). In relation to treatment, women were more likely to have undergone chemotherapy, surgery or surgery in combination with chemotherapy (p < 0.001) and to have response to the initial treatment (p < 0.001)., Conclusion: Incidence, morbidity and mortality rates of lung cancer in women of Brazil increased in the most recent years., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A study is presented on the resonance Raman (RR) spectrum based on fully anharmonic wave functions and energies obtained from ab initio multireference potential energy curves of diatomic systems. The vibrational problem is numerically solved using a variational stochastic method or the Cooley-Numerov method, as implemented in Le Roy's LEVEL program. Anharmonic Franck-Condon and Herzberg-Teller integrals are numerically evaluated, and the RR polarizability is calculated within the time-independent framework of the RR theory. At the harmonic level, the differential cross sections show faster convergence with respect to the number of intermediate vibrational states than what is obtained from anharmonic wave functions. Twice as many intermediate states are required to achieve the same convergence in the RR intensities as observed within the harmonic model. The anharmonic spectra evaluated for H 2 , C 2 , and O 2 molecules show that RR intensities are strongly affected by anharmonic effects. They differ from their harmonic counterparts not only in the position of the peaks but also in the absolute and relative intensities.

Purpose: Elderly patients with lung cancer tend to be undertreated in comparison to younger patients. The objective of this study is to compare treatment modalities offered to lung cancer patients from 70 years of age or more with patients under 70., Methods: For this study, an analytical cross-sectional epidemiological study conducted with data from the Brazilian hospital-based cancer registries between the years 2000 and 2011. In addition, odds ratios (OR) were calculated, with a 95% confidence intervals (95% CI), in conjunction with the construction of a logistic regression model., Results: By analyzing the records of 40,403 patients with lung cancer, we found that overall, patients from 70 years of age or more corresponded to 28.6% of the study population. Squamous cell carcinoma was the most common histological type among patients ≥70 years of age, whereas adenocarcinoma was the more prevalent type among younger patients. In comparison to younger patients, the older ones were treated less often (OR = 0.57; 95% CI: 0.52-0.62). Moreover, older patients were less likely to undergo surgery (OR = 0.69; 95% CI: 0.64-0.75), radiotherapy (OR = 0.86; 95% CI: 0.81-0.92), chemotherapy (OR = 0.61; 95% CI: 0.57-0.64), or an association of two or more treatment modalities (OR = 0.58; 95% CI: 0.54-0.62)., Conclusion: The study finds that Brazilian lung cancer patients ≥70 years of age are often undertreated and higher percentage of early death rates as compared to patients under 70. In regard to treatment, age alone should not determine whether patients with lung cancer are treated or not.

Morocco has been the subject of very few expeditions on the last century with the objective of studying small cicadas. In the summer of 2014 an expedition was carried out to Morocco to update our knowledge with acoustic recordings and genetic data of these poorly known species. We describe here two new small-sized cicadas that could not be directly assigned to any species of North African cicadas: Tettigettalna afroamissa sp. nov. and Berberigetta dimelodica gen. nov. & sp. nov. In respect to T. afroamissa it is the first species of the genus to be found outside Europe and we frame this taxon within the evolutionary history of the genus. Acoustic analysis of this species allows us to confidently separate T. afroamissa from its congeners. With B. dimelodica, a small species showing a remarkable calling song characterized by an abrupt frequency modulation, a new genus had to be erected. Bayesian inference and maximum likelihood phylogenetic analyses with DNA-barcode sequences of Cytochrome C Oxidase 1 support the monophyly of both species, their distinctness and revealed genetic structure within B. dimelodica. Alongside the descriptions we also provide GPS coordinates of collection points, distributions and habitat preferences.

Subtilisin-like proteases, also known as subtilases, are a very diverse family of serine peptidases present in many organisms. In grapevine, there are hints of the involvement of subtilases in defense mechanisms, but their role is not yet understood. The first characterization of the subtilase gene family was performed in 2014. However, simultaneously, the grapevine genome was re-annotated and several sequences were re-annotated or retrieved. We have performed a re-characterization of this family in grapevine and identified 82 genes coding for 97 putative proteins, as result of alternative splicing. All the subtilases identified present the characteristic S8 peptidase domain and the majority of them also have a pro-domain I9 inhibitor, a protease-associated (PA) domain, and a signal peptide for targeting to the secretory pathway. Phylogenetic studies revealed six subtilase groups denominated VvSBT 1 to VvSBT 6. As several evidences have highlighted the participation of plant subtilases in response to biotic stimulus, we have investigated subtilase participation in grapevine resistance to Plasmopara viticola , the causative agent of downy mildew. Fourteen grapevine subtilases presenting either high homology to P69C from tomato, SBT3.3 from Arabidopsis thaliana or located near the Resistance to P. viticola (RPV) locus were selected. Expression studies were conducted in the grapevine- P. viticola pathosystem with resistant and susceptible cultivars. Our results may indicate that some of grapevine subtilisins are potentially participating in the defense response against this biotrophic oomycete.

The cell wall (CW) is a dynamic structure that responds to stress. Water shortage (WS) impacts grapevine berry composition and its sensorial quality. In the present work, berry texture, skin CW composition, and expression of remodeling genes were investigated in two V. vinifera varieties, Touriga Nacional (TN) and Trincadeira (TR), under two water regimes, Full Irrigation (FI) and No Irrigation (NI). The global results allowed an evident separation between both varieties and the water treatments. WS resulted in increased anthocyanin contents in both varieties, reduced amounts in cellulose and lignin at maturation, but an increase in arabinose-containing polysaccharides more tightly bound to the CW in TR. In response to WS, the majority of the CW related genes were down-regulated in a variety dependent pattern. The results support the assumption that WS affects grape berries by stiffening the CW through alteration in pectin structure, supporting its involvement in responses to environmental conditions.

In this study, genetic differentiation between karyomorphs A (2n = 42) and D (2n = 39/40) of the wolf fish Hoplias malabaricus, which is comprised of several cryptic species that present a wide variety of diploid chromosome numbers and sex chromosome systems, resulting in the identification of seven distinct karyomorphs (A-G), was investigated using a combination of molecular and cytogenetic tools. Deep sequence divergences for both karyomorphs were observed and indicate a long period of reproductive isolation between karyomorphs A and D. Additionally, one individual with 61 chromosomes was identified, which, as far as is known, is the first case of natural triploidy resulting from the hybridization between these highly differentiated karyomorphs of H. malabaricus. Molecular and cytogenetic analyses revealed that this allotriploid specimen carries two sets of maternal chromosomes from karyomorph D (2n = 40) and one set of chromosomes from karyomorph A (n = 21). Moreover, ribosomal sites and active nucleolus organizer regions from both parental contributors were found in the triploid hybrid. Considering the significant genetic distances between karyomorphs A and D, one of the primary reasons for the lack of recurrent reports of hybridization in the H. malabaricus species complex may be due to post-zygotic barriers, such as hybrid sterility or unviability., (© 2014 The Fisheries Society of the British Isles.)

Background: The combination therapy for non-small-cell lung cancer (NSCLC) with platinum-based treatment is well known, but its utility in elderly has not been explored systematically., Aim: To examine whether aging compromises survival or exacerbates toxicity in patients with advanced lung cancer receiving platinum-based treatment., Methods: We performed a nested case-control study in a cohort of chemotherapy naïve patients enrolled January 1998-December 2003. Cases were consecutive patients over 70 at diagnosis with stage III or IV NSCLC. Controls were a subset of patients under 70 years matched by stage and year in which they had been treated. All patients received Cisplatin (80 mg/m2) or Carboplatin (4-6 AUC), every 4 weeks, followed by Vinorelbine (30 mg/m2) for a maximum of six courses. The medical history, physical examination and tumor imaging evaluation were performed at baseline and then monthly. Survival was calculated by Kaplan-Meier method and log-rank test was used for survival comparisons. Chi-squared test was used to compare side effects in the two groups., Results: A total of 419 patients were identified for the case-control study (205 elderly/214 young) with 3.6 cycles per patient, on average. The 2- and 3-year survival rates were 20.5% and 6.8% for elderly patients and 9.8% and 2.3% for younger patients (p=0.017 and 0.014, respectively for 2 and 3 years). The proportion of patients with adverse effects, either grade 3 or 4, was the same in both groups at 2 years (43.9% versus 43.9%; p=0.99)., Conclusions: Although elderly patients may self-select or be selected to be healthier, our findings suggest that elderly patients currently undergoing chemotherapy for lung cancer do as well or better than younger patients. Elderly age alone should not preclude patients from receiving platinum-based chemotherapy, since it seems well tolerated and effective in non-small-cell lung cancer among elderly patients.