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Bats are the second most diverse order of mammals and play a central role in ecosystem dynamics. They are also important reservoirs of potentially zoonotic microorganisms, of which rabies virus is the most lethal among the bat-transmitted zoonotic pathogens. Importantly, recent outbreaks of human rabies have been reported from the Brazilian Amazon. Here we present a survey of bat species and rabies virus (RABV) circulation in a bat assemblage in the Marajó region, northern Brazil. Using data from mist-net captures and bioacoustic sampling, 56 bat species were recorded along the Jacundá River basin over a 10-day expedition in November 2022. For the investigation of RABV, we used the direct fluorescent antibody test (DFAT) and the rapid fluorescent focus inhibition test (RFFIT). In total, 159 bat individuals from 22 species were investigated for RABV. Five adults of the common vampire bat, Desmodus rotundus, showed RABV-specific antibodies in serum samples. Additionally, we report on local residents with injuries caused by D. rotundus bites and the occurrence of colonies of non-hematophagous bats from different species roosting inside human residences. This scenario raises concerns about the risks of new cases of human rabies and other zoonotic diseases associated with bats in the region and highlights the need for epidemiological surveillance and mitigation measures to prevent outbreaks of emerging infectious diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Histiotus is a Neotropical genus of bat that currently includes 11 species. The systematics of Histiotus has been the focus of several studies over the last decades. However, no broad systematic revision has been made, and taxonomic issues such as synonymies, use of subspecies, and specimens that do not fit the description of valid species still persist, as pointed out by several authors. Histiotusalienus was described in 1916 and is known only by the holotype. Here we present a second record of H.alienus and an amended diagnosis of this species. We use qualitative, quantitative, and morphometric analyses based on data from 184 specimens of Histiotus and almost all valid species. Our amended diagnosis establishes the taxonomic limits of H.alienus , as well as a comprehensive comparison with congeners. We also explore new diagnostic characters for H.alienus and provide a few notes on the natural history of this species. Our results highlight skull similarities among Histiotus species and reinforce the usefulness of external morphology for their correct identification. Despite our new insights into the taxonomy of the genus, several taxonomic issues remain, and a comprehensive revision of the genus is needed., Competing Interests: The authors have declared that no competing interests exist., (Vinícius C. Cláudio, Brunna Almeida, Roberto L. M. Novaes, Marcos A. Navarro, Liliani M. Tiepolo, Ricardo Moratelli.)

In recent years, it became apparent that cancers either associated with viral infections or aberrantly expressing endogenous retroviral elements (EREs) are more immunogenic, exhibiting an intense intra-tumor immune cell infiltration characterized by a robust cytolytic apparatus. On the other hand, epigenetic regulation of EREs is crucial to maintain steady-state conditions and cell homeostasis. In line with this, epigenetic disruptions within steady-state cells can lead to cancer development and trigger the release of EREs into the cytoplasmic compartment. As such, detection of viral molecules by intracellular innate immune sensors leads to the production of type I and type III interferons that act to induce an antiviral state, thus restraining viral replication. This knowledge has recently gained momentum due to the possibility of triggering intratumoral activation of interferon responses, which could be used as an adjuvant to elicit strong anti-tumor immune responses that ultimately lead to a cascade of cytokine production. Accordingly, several therapeutic approaches are currently being tested using this rationale to improve responses to cancer immunotherapies. In this review, we discuss the immune mechanisms operating in viral infections, show evidence that exogenous viruses and endogenous retroviruses in cancer may enhance tumor immunogenicity, dissect the epigenetic control of EREs, and point to interferon pathway activation in the tumor milieu as a promising molecular predictive marker and immunotherapy target. Finally, we briefly discuss current strategies to modulate these responses within tumor tissues, including the clinical use of innate immune receptor agonists and DNA demethylating agents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Vitiello, Ferreira, Cordeiro de Lima and Medina.)

Typical carcinoids (TC), atypical carcinoids (AC), large cell neuroendocrine carcinomas (LCNEC), and small cell lung carcinomas (SCLC) encompass a bimodal spectrum of metastatic tumors with morphological, histological and histogenesis differences, The hierarchical structure reveals high cohesiveness between neoplastic cells by mechanical desmosomes barrier assembly in carcinoid tumors and LCNEC, while SCLC does not present an organoid arrangement in morphology, the neoplastic cells are less cohesive. However, the molecular mechanisms that lead to PNENs metastasis remain largely unknown and require further study. In this work, epithelial to mesenchymal transition (EMT) transcription factors were evaluated using a set of twenty-four patients with surgically resected PNENs, including carcinomas. Twelve EMT transcription factors ( BMP1 , BMP7 , CALD1 , CDH1 , COL3A1 , COL5A2 , EGFR , ERBB3 , PLEK2 , SNAI2 , STEAP1 , and TCF4 ) proved to be highly expressed among carcinomas and downregulated in carcinoid tumors, whereas upregulation of BMP1 , CDH2 , KRT14 and downregulation of CAV2 , DSC2 , IL1RN occurred in both histological subtypes. These EMT transcription factors identified were involved in proliferative signals, epithelium desmosomes assembly, and cell motility sequential steps that support PNENs invasion and metastasis in localized surgically resected primary tumor. We used a two-stage design where we first examined the candidate EMT transcription factors using a whole-genome screen, and subsequently, confirmed EMT-like changes by transmission electron microscopy and then, the EMT-related genes that were differentially expressed among PNENs subtypes were predicted through a Metascape analysis by in silico approach. A high expression of these EMT transcription factors was significantly associated with lymph node and distant metastasis. The sequential steps for invasion and metastasis were completed by an inverse association between functional barrier created by PD-L1 immunosuppressive molecule and EMT transcriptional factors. Our study implicates upregulation of EMT transcription factors to high proliferation rates, mechanical molecular barriers disassembly and increased cancer cell motility, as a critical molecular event leading to metastasis risk in PNENs thus emerging as a promising tool to select and customize therapy., Competing Interests: The author VCL was employed by the company Rede D’Or São Luiz S.A. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Prieto, Baldavira, Machado-Rugolo, Farhat, Olivieri, de Sá, da Silva, Balancin, Ab´Saber, Takagaki, Cordeiro de Lima and Capelozzi.)

The immune system plays a crucial role in cancer development either by fostering tumor growth or destroying tumor cells, which has open new avenues for cancer immunotherapy. It was only over the last decade that the role of B cells in controlling anti-tumor immune responses in the tumor milieu has begun to be appreciated. B and plasma cells can exert anti-tumor effects through antibody-dependent cell cytotoxicity (ADCC) and activation of the complement cascade, even though their effector functions extend beyond the classical humoral immunity. In tumor tissues, B cells can be found in lymphoid aggregates, known as tertiary lymphoid structures (TLSs), well-organized non-encapsulated structures composed of immune and stromal cells. These structures reflect a process of lymphoid neogenesis occurring in peripheral tissues upon long-lasting exposure to inflammatory signals. The TLS provides an area of intense B cell antigen presentation that can lead to optimal T cell activation and effector functions, as well as the generation of effector B cells, which can be further differentiated in either antibody-secreting plasma cells or memory B cells. Of clinical interest, the crosstalk between B cells and antigen-experienced and exhausted CD8 + T cells within mature TLS was recently associated with improved response to immune checkpoint blockade (ICB) in melanoma, sarcoma and lung cancer. Otherwise, B cells sparsely distributed in the tumor microenvironment or organized in immature TLSs were found to exert immune-regulatory functions, inhibiting anti-tumor immunity through the secretion of anti-inflammatory cytokines. Such phenotype might arise when B cells interact with malignant cells rather than T and dendritic cells. Differences in the spatial distribution likely underlie discrepancies between the role of B cells inferred from human samples or mouse models. Many fast-growing orthotopic tumors develop a malignant cell-rich bulk with reduced stroma and are devoid of TLSs, which highlights the importance of carefully selecting pre-clinical models. In summary, strategies that promote TLS formation in close proximity to tumor cells are likely to favor immunotherapy responses. Here, the cellular and molecular programs coordinating B cell development, activation and organization within TLSs will be reviewed, focusing on their translational relevance to cancer immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kinker, Vitiello, Ferreira, Chaves, Cordeiro de Lima and Medina.)

Background: Thymomas are a group of rare neoplasms of the anterior mediastinum. The objective of this study was to describe the demographics, clinical characteristics and treatment approaches in Latin America., Methods: This was a retrospective multicenter cohort study including patients with histologically proven thymomas diagnosed between 1997 and 2018. Demographics, clinicopathological characteristics and therapeutic outcomes were collected locally and analyzed in a centralized manner., Results: A total of 135 patients were included. Median age at diagnosis was 53 years old (19-84), 53.3% (n = 72) of patients were female and 87.4% had an ECOG performance score ranging from 0-1. A total of 47 patients (34.8%) had metastatic disease at diagnosis. Concurrent myasthenia gravis occurred in 21.5% of patients. Surgery was performed in 74 patients (54.8%), comprising 27 (20%) tumorectomies and 47 (34.8%) thymectomies. According to the Masaoka-Koga system, overall survival (OS) at five-years was 73.4%, 63.8% and 51%, at stages I-II, III-IVA and IVB, respectively (p = 0.005). Furthermore, patients with low lactate dehydrogenase (LDH) (≤373 IU/L) at baseline and myasthenia gravis concurrence showed significantly better OS (p = 0.001 and p = 0.008, respectively). In multivariate analysis, high LDH levels (HR 2.8 [95% confidence interval [CI]: 1.1-7.8]; p = 0.036) at baseline and not performing a surgical resection (HR 4.1 [95% CI: 1.3-12.7]; p = 0.016) were significantly associated with increased risk of death., Conclusions: Our data provides the largest insight into the clinical characteristics and outcomes of patients with thymomas in Latin America. Survival in patients with thymomas continues to be very favorable, especially when subjected to adequate local control., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: The aim of this study was to carry out a descriptive analysis of the somatic genetic profile and co-occurring mutations of non-small cell lung cancer (NSCLC) samples from patients tested with comprehensive genomic profiling (CGP)., Methods: This was a retrospective cross-sectional study of patients diagnosed with NSCLC from 2013 to 2018 in Brazil and whose samples were submitted to CGP (FoundationOne or FoundationACT) using either tumor or circulating tumor DNA (ctDNA) from plasma., Results: We recovered 513 CGP results from patients, 457 (89.1%) of which were from tumors and 56 (10.9%) from plasma. The median age of patients was 64 years old, of which 51.6% were males. TP53 mutations were identified in 53.6% of tumor samples, KRAS mutations in 24.2%, EGFR activating mutations were detected in 22.5%, STK11 mutations in 11.6%, PIK3CA mutations in 8.8%, ALK rearrangements in 5.4%, BRAF mutations in 5.2%, and ERBB2 alterations in 4.9%. The most commonly comutated gene was TP53. TP53 p.R337H was observed in 4.3% of samples and was associated with somatic mutations in EGFR and ERBB2 (P < 0.00001). Tumor mutational burden (TMB) analysis was available for 80.5% of samples tested, and 5.5% of samples had high TMB (≥ 20 mutations/Mb). In conclusion, this retrospective analysis of genomic data from NSCLC patients obtained by CGP showed that common abnormalities such as EGFR mutations and ALK rearrangements had similar frequency to those previously described by other groups using others strategies. Additionally, our data confirm an association between TP53 p.R337H, supposedly germline in nature, and somatic mutations in genes of the HER family., Key Points: SIGNIFICANT FINDINGS OF THE STUDY: This is the first report of the prevalence of driver mutations in Brazilian NSCLC patients using comprehensive genomic profiling (CGP). The frequency of the most common driver mutations in this population was similar to that previously described in Brazil., What This Study Adds: TP53 was the most commonly comutated gene across samples. TP53 p.R337H was associated with somatic mutations in EGFR and ERBB2. Most samples had low TMB; only 5.5% of samples had high TMB., (© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Myotis nesopolus currently comprises two subspecies. The nominate subspecies ( M. n. nesopolus ) occurs on the Caribbean islands of Curaçao and Bonaire, Netherlands Antilles, whereas M. n. larensis is known from mainland South America in northeastern Colombia and northwestern Venezuela. Our Maximum Likelihood phylogenetic analyses of cytochrome-b gene sequences recovered M. nesopolus as a paraphyletic group, with M. n. nesopolus and M. n. larensis as non-sister lineages. The haplotype network indicates that these two subspecies do not share any haplotypes and are in different evolutionary trajectories. Additionally, these two subspecies can be distinguished on the basis of qualitative and quantitative morphological traits. This pattern supports the recognition of M. nesopolus and M. larensis as full species. Our results also reveal that the assemblage of Caribbean Myotis do not form a monophyletic group. Caribbean species are phylogenetically close to mainland species from northern South America and Central America, suggesting that colonization of Caribbean islands happened multiple times.

Objectives: Lung cancer is a heterogeneous disease. Presentation and prognosis are known to vary according to several factors, such as genetic and demographic characteristics. Small-cell lung cancer incidence is increasing in never-smokers. However, the disease phenotype in this population is different compared with patients who have a smoking history. Material and Methods: To further investigate the clinical and genetic characteristics of this patient subgroup, a cohort of small cell lung cancer patients was divided into smokers ( n = 10) and never/ever-smokers ( n = 10). A somatic mutation profile was obtained using a comprehensive NGS assay. Clinical outcomes were compared using the Kaplan-Meier method and Cox proportional models. Results: Median age was 63 years (46-81), 40% were men, and 90% had extended disease. Smoker patients had significantly more cerebral metastases ( p = 0.04) and were older ( p = 0.03) compared to their non-smoker counterparts. For never/ever smokers, the main genetic mutations were TP53 (80%), RB1 (40%), CYLD (30%), and EGFR (30%). Smoker patients had more RB1 (80%, p = 0.04), CDKN2A (30%, p = 0.05), and CEBPA (30%, p = 0.05) mutations. Response rates to first-line therapy with etoposide plus cisplatin/carboplatin were 50% in smokers and 90% in never/ever smokers ( p = 0.141). Median overall survival was significantly longer in never smokers compared with smokers (29.1 months [23.5-34.6] vs. 17.3 months [4.8-29.7]; p = 0.0054). Never/ever smoking history (HR 0.543, 95% CI 0.41-0.80), limited-stage disease (HR 0.56, 95% CI 0.40-0.91) and response to first-line platinum-based chemotherapy (HR 0.63, 95% CI 0.60-0.92) were independently associated with good prognosis. Conclusion: Our data supports that never/ever smoker patients with small-cell lung cancer have better prognosis compared to their smoker counterparts. Further, patients with never/ever smoking history who present with small-cell lung cancer have a different mutation profile compared with smokers, including a high frequency of EGFR, MET , and SMAD4 mutations. Further studies are required to assess whether the differential mutation profile is a consequence of a diverse pathological mechanism for disease onset.

Bats play key ecological roles, also hosting many zoonotic pathogens. Neotropical bat microbiota is still poorly known. We speculate that their dietary habits strongly influence their microbiota richness and antibiotic-resistance patterns, which represent growing and serious public health and environmental issue. Here we describe the aerobic microbiota richness of bats from an Atlantic Forest remnant in Southeastern Brazil, and the antibiotic-resistance patterns of bacteria of clinical importance. Oral and rectal cavities of 113 bats from Carlos Botelho State Park were swabbed. Samples were plated on 5% sheep blood and MacConkey agar and identified by the MALDI-TOF technique. Antibiotic susceptibility tests were performed using Kirby-Bauer's antibiotic disc diffusion technique.We identified 596 isolates at the genus level and tentatively to the species level. Proteobacteria was the most abundant phylum in all the dietary guilds, representing 87% of the total identified samples. The most common bacteria within bat individuals were Escherichia coli, Klebsiella oxytoca and Serratia marcescens, and within bat species were Serratia marcescens, Pseudomonas sp. and Staphylococcus sp. Frugivores presented the most diverse microbiota. In general, the antibiogram results indicated a low occurrence of resistance on eigth potentially pathogenic bacteria species. The resistance to antibiotics found on our samples was related mostly to the intrinsic resistance of the tested species.The low occurrence of resistant bacteria in our samples could be related to the well preserved environment where bats were caught. Once the major causes of resistance-acquiring are related to anthropic activites, the controlled access of tourists on certain regions of the Park seems to be effectively protecting the environment., Competing Interests: The authors have declared that no competing interests exist.

Lasiurus ebenus was known only from the holotype, which was collected in 1991, in an Atlantic Forest remnant of Ilha do Cardoso State Park, southeastern Brazil. The species was described based on qualitative and quantitative morphological features. Since its original description, based on a single individual, the taxonomic status of Lasiurus ebenus has been questioned. Here we report a second record for the species that comes from Carlos Botelho State Park, São Paulo, ca. 100 km north from the type locality. This new record allowed us to confirm the validity of the species, by presenting additional data that fits in the distinction from sympatric congeners proposed on the original description of L. ebenus.

Baird et al. (2015) split Lasiurus into three distinct genera (Aeorestes, Dasypterus and Lasiurus) based on tree topology and divergence times for the tribe Lasiurini. This arrangement has not been widely adopted by the scientific community and was criticized by Ziegler et al. (2016). More recently, Baird et al. (2017) reinforced the taxonomic arrangement of Lasiurini comprised by three genera. Baird et al. (2015, 2017) provided the most comprehensive phylogenetic analyses of Lasiurus and offer important insights on the phylogeny and alpha-taxonomy of the group. However, we disagree with the taxonomic arrangement proposed at the genus level and explain our point below.