A Survey of PAPR Techniques Based on Machine Learning.

Orthogonal Frequency Division Multiplexing (OFDM) is the modulation technology used in Fourth Generation (4G) and Fifth Generation (5G) wireless communication systems, and it will likely be essential to Sixth Generation (6G) wireless communication systems. However, OFDM introduces a high Peak to Average Power Ratio (PAPR) in the time domain due to constructive interference among multiple subcarriers, increasing the complexity and cost of the amplifiers and, consequently, the cost and complexity of 6G networks. Therefore, the development of new solutions to reduce the PAPR in OFDM systems is crucial to 6G networks. The application of Machine Learning (ML) has emerged as a promising avenue for tackling PAPR issues. Along this line, this paper presents a comprehensive review of PAPR optimization techniques with a focus on ML approaches. From this survey, it becomes clear that ML solutions offer customized optimization, effective search space navigation, and real-time adaptability. In light of the demands of evolving 6G networks, integration of ML is a necessity to propel advancements and meet increasing prerequisites. This integration not only presents possibilities for PAPR reduction but also calls for continued exploration to harness its potential and ensure efficient and reliable communication within 6G networks.

An Automated Comparative Analysis of the Exudative Biomarkers in Neovascular Age-Related Macular Degeneration, The RAP Study: Report 6.

PURPOSE: To investigate differences in volume and distribution of the main exudative biomarkers across all types and subtypes of macular neovascularization (MNV) using artificial intelligence (AI). DESIGN: Cross-sectional study. METHODS: An AI-based analysis was conducted on 34,528 OCT B-scans consisting of 281 (250 unifocal, 31 multifocal) MNV3, 55 MNV2, and 121 (30 polypoidal, 91 non-polypoidal) MNV1 treatment-naive eyes. Means (SDs), medians and heat maps of cystic intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachments (PED), and hyperreflective foci (HRF) volumes, as well as retinal thickness (RT) were compared among MNV types and subtypes. RESULTS: MNV3 had the highest mean IRF with 291 (290) nL, RT with 357 (49) µm, and HRF with 80 (70) nL, P ≤ .05. MNV1 showed the greatest mean SRF with 492 (586) nL, whereas MNV3 exhibited the lowest with 218 (382) nL, P ≤ .05. Heat maps showed IRF confined to the center, whereas SRF was scattered in all types. SRF, HRF, and PED were more distributed in the temporal macular half in MNV3. Means of IRF, HRF, and PED were higher in the multifocal than in the unifocal MNV3 with 416 (309) nL,114 (95) nL, and 810 (850) nL, P ≤ .05. Compared to the non-polypoidal subtype, the polypoidal subtype had greater means of SRF with 695 (718) nL, HRF 69 (63) nL, RT 357 (45) µm, and PED 1115 (1170) nL, P ≤ .05. CONCLUSIONS: This novel quantitative AI analysis shows that SRF is a biomarker of choroidal origin in MNV1, whereas IRF, HRF, and RT are retinal biomarkers in MNV3. Polypoidal MNV1 and multifocal MNV3 present with higher exudation compared to other subtypes.

Spatial-temporal variations of metals and arsenic in sediments from the Doce River after the Fundão Dam rupture and their bioaccumulation in Corbicula fluminea.

The rupture of the Fundão dam in Brazil released tons of mining tailings into the Doce River Basin (DRB). This investigation aimed to determine the bioaccumulation of metals in soft tissues of the bivalve Corbicula fluminea exposed to sediments collected in the DRB in four periods (just after, 1, 3, and 3.5 years after the dam rupture). In the exposure bioassays, the concentrations of Al, As, Cd, Cr, Cu, Fe, Mn, Ni, Pb, and Zn in sediments and bivalve soft tissues were quantified. The concentration of some elements (As, Cd, Mn, and Al) in sediments exceeded the federal limits or regional backgrounds at some sampling sites, but their concentrations tended to decrease over time. However, higher concentrations of many elements were detected in the winter of 2019. Several elements were detected in C. fluminea soft tissues, but the bioaccumulation factors were generally low or not related to those elements associated with the ore tailings, evidencing that the bioavailability of metals to bivalves, in laboratory conditions, was limited. Integr Environ Assess Manag 2024;20:87-98. © 2023 SETAC.

Reverse Genetics Systems for Filoviruses.

Filoviruses are causative agents of severe hemorrhagic fevers with high case fatality rates in humans. For studies of virus biology and the subsequent development of countermeasures, reverse genetic systems, and especially those facilitating the generation of recombinant filoviruses, are indispensable. Here, we describe the generation of recombinant filoviruses from cDNA.

Potential of olfactory neuroepithelial cells as a model to study schizophrenia: A focus on GPCRs (Review).

Schizophrenia (SZ) is a multifactorial disorder characterized by volume reduction in gray and white matter, oxidative stress, neuroinflammation, altered neurotransmission, as well as molecular deficiencies such as punctual mutation in Disrupted­in­Schizophrenia 1 protein. In this regard, it is essential to understand the underlying molecular disturbances to determine the pathophysiological mechanisms of the disease. The signaling pathways activated by G protein­coupled receptors (GPCRs) are key molecular signaling pathways altered in SZ. Convenient models need to be designed and validated to study these processes and mechanisms at the cellular level. Cultured olfactory stem cells are used to investigate neural molecular and cellular alterations related to the pathophysiology of SZ. Multipotent human olfactory stem cells are undifferentiated and express GPCRs involved in numerous physiological functions such as proliferation, differentiation and bioenergetics. The use of olfactory stem cells obtained from patients with SZ may identify alterations in GPCR signaling that underlie dysfunctional processes in both undifferentiated and specialized neurons or derived neuroglia. The present review aimed to analyze the role of GPCRs and their signaling in the pathophysiology of SZ. Culture of olfactory epithelial cells constitutes a suitable model to study SZ and other psychiatric disorders at the cellular level.

Hypoxia Induces Alterations in the Circadian Rhythm in Patients with Chronic Respiratory Diseases.

The function of the circadian cycle is to determine the natural 24 h biological rhythm, which includes physiological, metabolic, and hormonal changes that occur daily in the body. This cycle is controlled by an internal biological clock that is present in the body's tissues and helps regulate various processes such as sleeping, eating, and others. Interestingly, animal models have provided enough evidence to assume that the alteration in the circadian system leads to the appearance of numerous diseases. Alterations in breathing patterns in lung diseases can modify oxygenation and the circadian cycles; however, the response mechanisms to hypoxia and their relationship with the clock genes are not fully understood. Hypoxia is a condition in which the lack of adequate oxygenation promotes adaptation mechanisms and is related to several genes that regulate the circadian cycles, the latter because hypoxia alters the production of melatonin and brain physiology. Additionally, the lack of oxygen alters the expression of clock genes, leading to an alteration in the regularity and precision of the circadian cycle. In this sense, hypoxia is a hallmark of a wide variety of lung diseases. In the present work, we intended to review the functional repercussions of hypoxia in the presence of asthma, chronic obstructive sleep apnea, lung cancer, idiopathic pulmonary fibrosis, obstructive sleep apnea, influenza, and COVID-19 and its repercussions on the circadian cycles.

Phytoestrogen-Based Hormonal Replacement Therapy Could Benefit Women Suffering Late-Onset Asthma.

It has been observed that plasmatic concentrations of estrogens, progesterone, or both correlate with symptoms in asthmatic women. Fluctuations in female sex steroid concentrations during menstrual periods are closely related to asthma symptoms, while menopause induces severe physiological changes that might require hormonal replacement therapy (HRT), that could influence asthma symptoms in these women. Late-onset asthma (LOA) has been categorized as a specific asthmatic phenotype that includes menopausal women and novel research regarding therapeutic alternatives that might provide relief to asthmatic women suffering LOA warrants more thorough and comprehensive analysis. Therefore, the present review proposes phytoestrogens as a promising HRT that might provide these females with relief for both their menopause and asthma symptoms. Besides their well-recognized anti-inflammatory and antioxidant capacities, phytoestrogens activate estrogen receptors and promote mild hormone-like responses that benefit postmenopausal women, particularly asthmatics, constituting therefore a very attractive potential therapy largely due to their low toxicity and scarce side effects.

CTX-M-producing Escherichia coli ST602 carrying a wide resistome in South American wild birds: Another pandemic clone of One Health concern.

Wild birds have emerged as novel reservoirs and potential spreaders of antibiotic-resistant priority pathogens, being proposed as sentinels of anthropogenic activities related to the use of antimicrobial compounds. The aim of this study was to investigate the occurrence and genomic features of extended-spectrum ß-lactamase (ESBL)-producing bacteria in wild birds in South America. In this regard, we have identified two ESBL (CTX-M-55 and CTX-M-65)-positive Escherichia coli (UNB7 and GP188 strains) colonizing Creamy-bellied Thrush (Turdus amaurochalinus) and Variable Hawk (Geranoaetus polyosoma) inhabiting synanthropic and wildlife environments from Brazil and Chile, respectively. Whole-genome sequence (WGS) analysis revealed that E. coli UNB7 and GP188 belonged to the globally disseminated clone ST602, carrying a wide resistome against antibiotics (ß-lactams), heavy metals (arsenic, copper, mercury), disinfectants (quaternary ammonium compounds), and pesticides (glyphosate). Additionally, E. coli UNB7 and GP188 strains harbored virulence genes encoding hemolysin E, type II and III secretion systems, increased serum survival, adhesins and siderophores. SNP-based phylogenomic analysis, using an international genome database, revealed genomic relatedness (19-363 SNP differences) of GP188 with livestock and poultry strains, and genomic relatedness (61-318 differences) of UNB7 with environmental, human and livestock strains (Table S1), whereas phylogeographical analysis confirmed successful expansion of ST602 as a global clone of One Health concern. In summary, our results support that ESBL-producing E. coli ST602 harboring a wide resistome and virulome have begun colonizing wild birds in South America, highlighting a potential new reservoir of critical priority pathogens.

N6-methyladenosine is required for efficient RNA synthesis of Ebola virus and other haemorrhagic fever viruses.

N6-methyladenosine (m6A) is one of the most abundant modifications of cellular RNA, where it serves various functions. m6A methylation of many viral RNA species has also been described; however, little is known about the m6A epitranscriptome of haemorrhagic fever-causing viruses like Ebola virus (EBOV). Here, we analysed the importance of the methyltransferase METTL3 for the life cycle of this virus. We found that METTL3 interacts with the EBOV nucleoprotein and the transcriptional activator VP30 to support viral RNA synthesis, and that METTL3 is recruited into EBOV inclusions bodies, where viral RNA synthesis occurs. Analysis of the m6A methylation pattern of EBOV mRNAs showed that they are methylated by METTL3. Further studies revealed that METTL3 interaction with the viral nucleoprotein, as well as its importance for RNA synthesis and protein expression, is also observed for other haemorrhagic fever viruses such as Junín virus (JUNV) and Crimean-Congo haemorrhagic fever virus (CCHFV). The negative effects on viral RNA synthesis due to loss of m6A methylation are independent of innate immune sensing, as METTL3 knockout did not affect type I interferon induction in response to viral RNA synthesis or infection. Our results suggest a novel function for m6A that is conserved among diverse haemorrhagic fever-causing viruses (i.e. EBOV, JUNV and CCHFV), making METTL3 a promising target for broadly-acting antivirals.

Ebola virus inclusion bodies are liquid organelles whose formation is facilitated by nucleoprotein oligomerization.

Viral RNA synthesis of several non-segmented, negative-sense RNA viruses (NNSVs) takes place in inclusion bodies (IBs) that show properties of liquid organelles, which are formed by liquid-liquid phase separation of scaffold proteins. It is believed that this is driven by intrinsically disordered regions (IDRs) and/or multiple copies of interaction domains, which for NNSVs are usually located in their nucleo - and phosphoproteins. In contrast to other NNSVs, the Ebola virus (EBOV) nucleoprotein NP alone is sufficient to form IBs without the need for a phosphoprotein, and to facilitate the recruitment of other viral proteins into these structures. While it has been proposed that also EBOV IBs are liquid organelles, this has so far not been formally demonstrated. Here we used a combination of live cell microscopy, fluorescence recovery after photobleaching assays, and mutagenesis approaches together with reverse genetics-based generation of recombinant viruses to study the formation of EBOV IBs. Our results demonstrate that EBOV IBs are indeed liquid organelles, and that oligomerization but not IDRs of the EBOV nucleoprotein plays a key role in their formation. Additionally, VP35 (often considered the phosphoprotein-equivalent of EBOV) is not essential for IB formation, but alters their liquid behaviour. These findings define the molecular mechanism for the formation of EBOV IBs, which play a central role in the life cycle of this deadly virus.

Synovial Fluid Biomarkers for the Diagnosis of Periprosthetic Joint Infection-A Systematic Review and Meta-Analysis of Their Diagnostic Accuracy According to Different Definitions.

BACKGROUND: Different synovial fluid biomarkers have emerged to improve periprosthetic joint infection (PJI) diagnosis. The goals of this paper were (i) to assess their diagnostic accuracy and (ii) to evaluate their performance according to different PJI definitions. METHODS: A systematic review and meta-analysis was performed using studies that reported diagnostic accuracy of synovial fluid biomarkers using validated PJI definitions published from 2010 to March 2022. A database search was performed through PubMed, Ovid MEDLINE, Central, and Embase. The search identified 43 different biomarkers with four being the more commonly studied, with 75 papers overall: alpha-defensin; leukocyte esterase; synovial fluid C-reactive protein; and calprotectin. RESULTS: Overall accuracy was higher for calprotectin, followed by alpha-defensin, leukocyte esterase, and synovial fluid C-reactive protein with sensitivities of 78 to 92% and specificities of 90 to 95%. Their diagnostic performance was different according to which definition was adopted as the reference. Specificity was consistently high across definitions for all four biomarkers. Sensitivity varied the most with lower values for the more sensitive European Bone and Joint Infection Society or Infectious Diseases Society of America definitions with higher values for the Musculoskeletal Infection Society definition. The International Consensus Meeting 2018 definition showed intermediate values. CONCLUSION: All evaluated biomarkers had good specificity and sensitivity, making their use acceptable in the diagnosis of PJI. Biomarkers perform differently according to the selected PJI definitions.

Performance of retinal fluid monitoring in OCT imaging by automated deep learning versus human expert grading in neovascular AMD.

PURPOSE: To evaluate the reliability of automated fluid detection in identifying retinal fluid activity in OCT scans of patients treated with anti-VEGF therapy for neovascular age-related macular degeneration by correlating human expert and automated measurements with central retinal subfield thickness (CSFT) and fluid volume values. METHODS: We utilized an automated deep learning approach to quantify macular fluid in SD-OCT volumes (Cirrus, Spectralis, Topcon) from patients of HAWK and HARRIER Studies. Three-dimensional volumes for IRF and SRF were measured at baseline and under therapy in the central millimeter and compared to fluid gradings, CSFT and foveal centerpoint thickness (CPT) values measured by the Vienna Reading Center. RESULTS: 41.906 SD-OCT volume scans were included into the analysis. Concordance between human expert grading and automated algorithm performance reached AUC values of 0.93/0.85 for IRF and 0.87 for SRF in HARRIER/HAWK in the central millimeter. IRF volumes showed a moderate correlation with CSFT at baseline (HAWK: r = 0.54; HARRIER: r = 0.62) and weaker correlation under therapy (HAWK: r = 0.44; HARRIER: r = 0.34). SRF and CSFT correlations were low at baseline (HAWK: r = 0.29; HARRIER: r = 0.22) and under therapy (HAWK: r = 0.38; HARRIER: r = 0.45). The residual standard error (IRF: 75.90 µm; SRF: 95.26 µm) and marginal residual standard deviations (IRF: 46.35 µm; SRF: 44.19 µm) of fluid volume were high compared to the range of CSFT values. CONCLUSION: Deep learning-based segmentation of retinal fluid performs reliably on OCT images. CSFT values are weak indicators for fluid activity in nAMD. Automated quantification of fluid types, highlight the potential of deep learning-based approaches to objectively monitor anti-VEGF therapy.

Extending records of albinism and skin disorders in American cownose rays to southeastern Brazil.

Albinism is a genetic condition expressed as a lack of integumentary and retinal melanin. Although documented across many vertebrate species, albinism and other skin disorders are rarely observed in elasmobranchs (sharks and rays). The present study describes the first confirmed case of albinism in American cownose ray (Rhinoptera bonasus), and three other juveniles of the species with undetermined skin disorders observed in São Paulo, southeastern Brazil. Pigmentation disorders have already been observed in American cownose rays from the North Atlantic, including two cases of leucism and a possible albinism. Based on the results, it was discussed the possible consequences of albinism for the ray survival as well as the possible causes for the undetermined skin disorders.

Estrogenic Modulation of Ionic Channels, Pumps and Exchangers in Airway Smooth Muscle.

To preserve ionic homeostasis (primarily Ca2+, K+, Na+, and Cl-), in the airway smooth muscle (ASM) numerous transporters (channels, exchangers, and pumps) regulate the influx and efflux of these ions. Many of intracellular processes depend on continuous ionic permeation, including exocytosis, contraction, metabolism, transcription, fecundation, proliferation, and apoptosis. These mechanisms are precisely regulated, for instance, through hormonal activity. The lipophilic nature of steroidal hormones allows their free transit into the cell where, in most cases, they occupy their cognate receptor to generate genomic actions. In the sense, estrogens can stimulate development, proliferation, migration, and survival of target cells, including in lung physiology. Non-genomic actions on the other hand do not imply estrogen's intracellular receptor occupation, nor do they initiate transcription and are mostly immediate to the stimulus. Among estrogen's non genomic responses regulation of calcium homeostasis and contraction and relaxation processes play paramount roles in ASM. On the other hand, disruption of calcium homeostasis has been closely associated with some ASM pathological mechanism. Thus, this paper intends to summarize the effects of estrogen on ionic handling proteins in ASM. The considerable diversity, range and power of estrogens regulates ionic homeostasis through genomic and non-genomic mechanisms.

Combination of vitamin D and probiotics inhibits chemically induced colorectal carcinogenesis in Wistar rats.

The modulation of inflammatory elements, cell differentiation and proliferation by vitamin D and the role of probiotics in the intestinal microbiota and immunogenic response have sparked interest in the application of both in chemotherapeutics and chemoprevention of colorectal tumors. AIMS: The present study aimed to investigate the effects of isolated and/or combined treatment of vitamin D3 and probiotics on colorectal carcinogenesis. MAIN METHODS: Pre-neoplastic lesions were induced with 1,2-dimethylhydrazine in the colon of Wistar rats, which were treated with probiotics and/or vitamin D in three different approaches (simultaneous, pre-, and post-treatment). We investigated the frequency of aberrant crypt foci (ACF) and aberrant crypt (AC) in the distal colon, fecal microbiome composition, gene and protein expression through immunohistochemical and RT-PCR assays, and general toxicity through water consumption and weight gain monitoring. KEY FINDINGS: Results confirm the systemic safety of treatments, and show a protective effect of vitamin D and probiotics in all approaches studied, as well as in combined treatments, with predominance of different bacterial phyla compared to controls. Treated groups show different levels of Nrf2, GST, COX2, iNOS, ß-catenin and PCNA expression. SIGNIFICANCE: These experimental conditions explore the combination of vitamin D and probiotics supplementation at low doses over pathways involved in distinct stages of colorectal carcinogenesis, with results supporting its application in prevention and long-term strategies.

Ophthalmic and immunopathological characterization of systemic infectious diseases in cats.

Ocular involvement in systemic diseases is frequent in cats; however, without concurrent clinical and ophthalmic examinations with gross and/or histologic analysis of the eye, these findings can be underdiagnosed. This article aims to provide gross, histologic, and immunohistochemical characteristics of ocular lesions from cats submitted to necropsy, focusing on those caused by systemic infectious agents. Cats that died due to a systemic infectious disease were selected based on necropsy diagnosis and presence of ocular lesions. Gross, histologic, and immunohistochemical findings were recorded. From April 2018 to September 2019, 849 eyes of 428 cats were evaluated. Histologic abnormalities were seen in 29% of cases, which were classified as inflammatory (41%), neoplastic (32%), degenerative (19%), and metabolic/vascular (8%). Macroscopic changes were present in one-third of eyes with histologic lesions. Of these, 40% were attributed to inflammatory or neoplastic diseases associated with infectious agents. The most important infectious agents causing ocular disease in this study were feline leukemia virus, feline infectious peritonitis virus, and Cryptococcus sp. The most common ocular abnormalities associated with infectious agents were uveitis (anterior, posterior, or panuveitis), optic neuritis, and meningitis of the optic nerve. Ocular lesions secondary to systemic infections in cats are frequent; however, these are not always diagnosed because gross lesions are less common than histologic lesions. Therefore, both gross and histologic evaluation of the eyes of cats is recommended, mainly for cases in which the clinical suspicion or necropsy diagnosis suggests that an infectious agent might be related to the cause of death.

A protective measles virus-derived vaccine inducing long-lasting immune responses against influenza A virus H7N9.

A novel Influenza A virus (subtype H7N9) emerged in spring 2013 and caused considerable mortality in zoonotically infected patients. To be prepared for potential pandemics, broadly effective and safe vaccines are crucial. Recombinant measles virus (MeV) encoding antigens of foreign pathogens constitutes a promising vector platform to generate novel vaccines. To characterize the efficacy of H7N9 antigens in a prototypic vaccine platform technology, we generated MeVs encoding either neuraminidase (N9) or hemagglutinin (H7). Moraten vaccine strain-derived vaccine candidates were rescued; they replicated with efficiency comparable to that of the measles vaccine, robustly expressed H7 and N9, and were genetically stable over 10 passages. Immunization of MeV-susceptible mice triggered the production of antibodies against H7 and N9, including hemagglutination-inhibiting and neutralizing antibodies induced by MVvac2-H7(P) and neuraminidase-inhibiting antibodies by MVvac2-N9(P). Vaccinated mice also developed long-lasting H7- and N9-specific T cells. Both MVvac2-H7(P) and MVvac2-N9(P)-vaccinated mice were protected from lethal H7N9 challenge.

Pathological and immunohistochemical characterization of pancreatic carcinoma in cats.

The aim of this study was to characterize the pathological and immunohistochemical aspects of pancreatic carcinoma in cats, through a retrospective study. From January 2010 to December 2021, 1,908 cat necropsies were performed, in which 20 cases of exocrine pancreatic neoplasia were diagnosed (1.04%). Affected cats were mature adults and seniors, except for one 1-year-old cat. In 11 cases the neoplasm was a soft, focal nodule on the left (8/11) or right (3/11) lobe. In nine cases there were multifocal nodules throughout the pancreatic parenchyma. The size of the single masses ranged from 2 to 12 cm, and the multifocal masses from 0.5 to 2 cm. The most frequent tumour type was acinar carcinoma (11/20), followed by ductal carcinoma (8/20), undifferentiated carcinoma (1/20) and carcinosarcoma (1/20). On immunohistochemical evaluation, all the neoplasms were remarkably reactive to pancytokeratin antibody. The ductal carcinomas were strongly reactive for cytokeratins 7 and 20, which proved to be a good marker for pancreatic ductal carcinoma in cats. The main form of metastasis was abdominal carcinomatosis, with a marked invasion of blood and lymphatic vessels by neoplastic cells. Our findings reinforce the fact that pancreatic carcinoma should be rated highly in the differential diagnosis in mature adult and senior cats with abdominal masses, ascites and/or jaundice.