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Background: Lung cancer constitutes the leading cause of cancer mortality. High levels of endothelin-1 (ET-1), its cognate receptor ET A R and its activating enzyme, the endothelin-converting enzyme-1 (ECE-1), have been reported in several cancer types, including lung cancer. ECE-1 comprises four isoforms, which only differ in their cytoplasmic N-terminus. Protein kinase CK2 phosphorylates the N-terminus of isoform ECE-1c, increasing its stability and leading to enhanced invasiveness in glioblastoma and colorectal cancer cells, which is believed to be mediated by the amino acid residue Lys-6, a conserved putative ubiquitination site neighboring the CK2-phosphorylated residues Ser-18 and Ser-20. Whether Lys-6 is linked to the acquisition of a cancer stem cell (CSC)-like phenotype and aggressiveness in human non-small cell lung cancer (NSCLC) cells has not been studied., Methods: In order to establish the role of Lys-6 in the stability of ECE-1c and its involvement in lung cancer aggressiveness, we mutated this residue to a non-ubiquitinable arginine and constitutively expressed the wild-type (ECE-1c WT ) and mutant (ECE-1c K6R ) proteins in A549 and H1299 human NSCLC cells by lentiviral transduction. We determined the protein stability of these clones alone or in the presence of the CK2 inhibitor silmitasertib, compared to ECE-1c WT and mock-transduced cells. In addition, the concentration of secreted ET-1 in the growth media was determined by ELISA. Expression of stemness genes were determined by Western blot and RT-qPCR. Chemoresistance to cisplatin was studied by MTS viability assay. Migration and invasion were measured through transwell and Matrigel assays, respectively, and the side-population was determined using flow cytometry., Results: ECE-1c K6R displayed higher stability in NSCLC cells compared to ECE-1c WT -expressing cells, but ET-1 secreted levels showed no difference up to 48 h. Most importantly, ECE-1c K6R promoted expression of the stemness genes c-Myc, Sox-2, Oct-4, CD44 and CD133, which enhance cellular self-renewal capability. Also, the ECE-1c K6R -expressing cells showed higher cisplatin chemoresistance, correlating with an augmented side-population abundance due to the increased expression of the ABCG2 efflux pump. Finally, the ECE-1c K6R -expressing cells showed enhanced invasiveness, which correlated with the regulated expression of known EMT markers., Conclusions: Our findings suggest an important role of ECE-1c in lung cancer. ECE-1c is key in a non-canonical ET-1-independent mechanism which triggers a CSC-like phenotype, leading to enhanced lung cancer aggressiveness. Underlying this mechanism, ECE-1c is stabilized upon phosphorylation by CK2, which is upregulated in many cancers. Thus, phospho-ECE-1c may be considered as a novel prognostic biomarker of recurrence, as well as the CK2 inhibitor silmitasertib as a potential therapy for lung cancer patients., (© 2024. The Author(s).)

Little is known about differences in child developmental vulnerability before school entry according to maternal birthplace and sex. Official immigration records were linked with the Early Development Instrument assessments among children in kindergarten in the province of Manitoba, Canada (2005-2017). Logistic regression was used to estimate odds ratios of vulnerability in five developmental domains associated with maternal birthplace and child sex. Children of immigrant mothers from most birthplaces had higher adjusted odds of developmental vulnerability than non-immigrants in domains related to language and communication skills, except those of the rest of North America & Oceania. Children of Sub-Saharan African mothers were more vulnerable in four domains. Boys were consistently more vulnerable than girls across domains and maternal birthplaces. Children of immigrant mothers exhibited higher developmental vulnerability than non-immigrants in domains related to language and communication skills, potentially reflecting exposure to English and French as second languages., (© 2024. The Author(s).)

The neotropical fish genus Astyanax (Characidae) and its associated helminths migrated northward from South America following the Great American Biotic Interchange (GABI): ca. 150 Astyanax spp. are found throughout South and Central America, up to the Mexico-USA border. Most characids are distributed south of the Trans-Mexican Volcanic Belt (TMVB), which bisects the country and represents a major transition zone between the neotropical and nearctic realms. Here, we characterize parasites of the monogenean genus Gyrodactylus infecting Astyanax spp. in Mexico: Astyanax aeneus south of the TMBV, Astyanax mexicanus north of it. Based on morphological, phylogenetic (internal transcribed spacer (ITS) and cytochrome oxidase subunit II (cox 2)) and statistical analyses of morphometric data, we confirmed the validity of Gyrodactylus pakan and Gyrodactylus teken, and erected two new species, Gyrodactylus aphaa n. sp. and Gyrodactylus ricardoi n. sp. These four gyrodactylids are part of a complex of morphologically cryptic species, which are phylogenetically closely related to each other, and sister species to Gyrodactylus carolinae and Gyrodactylus heteracanthus, parasites of characins in Brazil. Four gyrodactylid lineages (G. pakan, G. ricardoi n. sp., G. teken, Gyrodactylus sp. A) are distributed north of the TMVB; G. pakan is also widely distributed south of the TMVB, together with G. aphaa n. sp. Based on the ITS phylogeny, Brazilian parasites form a sister clade to all Mexican gyrodactylids, whose derived clades are distributed in progressively more northerly latitudes in Mexico - the three most-derived species north of the TMVB. This would suggest that gyrodactylid species diverged gradually, presumably as their characid fish hosts colonized and adapted to new environments north of the TMVB., (Copyright © 2024 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.)

Disruption of the class I human leukocyte antigen (HLA) molecules has important implications for immune evasion and tumor evolution. We developed major histocompatibility complex loss of heterozygosity (LOH), allele-specific mutation and measurement of expression and repression (MHC Hammer). We identified extensive variability in HLA allelic expression and pervasive HLA alternative splicing in normal lung and breast tissue. In lung TRACERx and lung and breast TCGA cohorts, 61% of lung adenocarcinoma (LUAD), 76% of lung squamous cell carcinoma (LUSC) and 35% of estrogen receptor-positive (ER+) cancers harbored class I HLA transcriptional repression, while HLA tumor-enriched alternative splicing occurred in 31%, 11% and 15% of LUAD, LUSC and ER+ cancers. Consistent with the importance of HLA dysfunction in tumor evolution, in LUADs, HLA LOH was associated with metastasis and LUAD primary tumor regions seeding a metastasis had a lower effective neoantigen burden than non-seeding regions. These data highlight the extent and importance of HLA transcriptomic disruption, including repression and alternative splicing in cancer evolution., (© 2024. The Author(s).)

In Chile, limited information is available on colorants in commonly consumed foods among vulnerable age groups. We developed and validated a rapid HPLC-DAD method to simultaneously evaluate 11 synthetic colorants in candies, beverages, ice cream, and cereals. The method exhibited excellent analytical performance for all 11 colorants with LOD (0.44 - 1.55 mgL -1 ), LOQ v(1.32 - 4.70 mgL -1 ), precision (4.0 and 7.3% RSD), and recovery (80 - 105%) in fortified matrices (10-50-100 mgL -1 ). The highest detection frequencies were as follows: cereals > candies > beverages > ice cream. Sunset Yellow was the most prevalent colorant in all food matrices, followed by Allura Red and Azorubine. Positive samples contained between 1 and 5 synthetic colorants. With the exception of cereals, the colorant concentrations in the remaining matrices exceeded the Codex Alimentarius regulations and the values reported in other studies worldwide, indicating the Chilean population is at risk., 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 Ltd. All rights reserved.)

Metastable states are identified in the Ising model with competition between the Glauber and Kawasaki dynamics. The model of interaction between magnetic moments was implemented on a network where the degree distribution follows a power law of the form P(k)∼k^{-α}. The evolution toward the stationary state occurred through the competition between two dynamics, driving the system out of equilibrium. In this competition, with probability q, the system was simulated in contact with a heat bath at temperature T by the Glauber dynamics, while with probability 1-q, the system experienced an external energy influx governed by the Kawasaki dynamics. The phase diagrams of T as a function of q were obtained, which are dependent on the initial state of the system, and exhibit first- and second-order phase transitions. In all diagrams, for intermediate values of T, the phenomenon of self-organization between the ordered phases was observed. In the regions of second-order phase transitions, we obtained the critical exponents of the order parameter β, susceptibility γ, and correlation length ν. Furthermore, in the regions of first-order phase transitions, we have demonstrated the instability due to transitions between ordered phases through hysteresislike curves of the order parameter, in addition to the existence of absorbing states. We also estimated the value of tricritical points when the discontinuity in the order parameter in the phase transitions was no longer observed.

Family Parvoviridae consists of small, non-enveloped viruses with linear, single-stranded DNA genomes of approximately 4-6 kilobases, subdivided into three subfamilies, Parvovirinae , Densovirinae, and Hamaparvovirinae , and unassigned genus Metalloincertoparvovirus . Parvoviruses of aquatic animals infect crustaceans, mollusks, and finfish. This review describes these parvoviruses, which are highly host-specific and associated with mass morbidity and mortality in both farmed and wild aquatic animals. They include Cherax quadricarinatus densovirus (CqDV) in freshwater crayfish in Queensland, Australia; sea star-associated densovirus (SSaDV) in sunflower sea star on the Northeastern Pacific Coast; Clinch densovirus 1 in freshwater mussels in the Clinch River, Virginia, and Tennessee, USA, in subfamily Densovirinae ; hepatopancreatic parvovirus (HPV) and infectious hypodermal and hematopoietic necrosis virus (IHHNV) in farmed shrimp worldwide; Syngnathid ichthamaparvovirus 1 in gulf pipefish in the Gulf of Mexico and parts of South America; tilapia parvovirus (TiPV) in farmed tilapia in China, Thailand, and India, in the subfamily Hamaparvovirinae ; and Penaeus monodon metallodensovirus (PmMDV) in Vietnamese P. monodon , in unassigned genus Metalloincertoparvovirus . Also included in the family Parvoviridae are novel parvoviruses detected in both diseased and healthy animals using metagenomic sequencing, such as zander parvovirus from zander in Hungary and salmon parvovirus from sockeye salmon smolts in British Columbia, Canada.

Increasing evidence supports the hypothesis that cancer progression is under mitochondrial control. Mitochondrial fission plays a pivotal role in the maintenance of cancer cell homeostasis. The inhibition of DRP1, the main regulator of mitochondrial fission, with the mitochondrial division inhibitor (mdivi-1) had been associated with cancer cell sensitivity to chemotherapeutics and decrease proliferation. Here, using breast cancer cells we find that mdivi-1 induces the detachment of the cells, leading to a bulk of floating cells that conserved their viability. Despite a decrease in their proliferative and clonogenic capabilities, these floating cells maintain the capacity to re-adhere upon re-seeding and retain their migratory and invasive potential. Interestingly, the cell detachment induced by mdivi-1 is independent of DRP1 but relies on inhibition of mitochondrial complex I. Furthermore, mdivi-1 induces cell detachment rely on glucose and the pentose phosphate pathway. Our data evidence a novel DRP1-independent effect of mdivi-1 in the attachment of cancer cells. The generation of floating viable cells restricts the use of mdivi-1 as a therapeutic agent and demonstrates that mdivi-1 effect on cancer cells are more complex than anticipated., (© 2024. The Author(s).)

Tumor hypoxia has been associated with cancer progression, angiogenesis, and metastasis via modifications in the release and cargo composition of extracellular vesicles secreted by tumor cells. Indeed, hypoxic extracellular vesicles are known to trigger a variety of angiogenic responses via different mechanisms. We recently showed that hypoxia promotes endosomal signaling in tumor cells via HIF-1α-dependent induction of the guanine exchange factor ALS2, which activates Rab5, leading to downstream events involved in cell migration and invasion. Since Rab5-dependent signaling is required for endothelial cell migration and angiogenesis, we explored the possibility that hypoxia promotes the release of small extracellular vesicles containing ALS2, which in turn activate Rab5 in recipient endothelial cells leading to pro-angiogenic properties. In doing so, we found that hypoxia promoted ALS2 expression and incorporation as cargo within small extracellular vesicles, leading to subsequent transfer to recipient endothelial cells and promoting cell migration, tube formation, and downstream Rab5 activation. Consequently, ALS2-containing small extracellular vesicles increased early endosome size and number in recipient endothelial cells, which was followed by subsequent sequestration of components of the β-catenin destruction complex within endosomal compartments, leading to stabilization and nuclear localization of β-catenin. These events converged in the expression of β-catenin target genes involved in angiogenesis. Knockdown of ALS2 in donor tumor cells precluded its incorporation into small extracellular vesicles, preventing Rab5-downstream events and endothelial cell responses, which depended on Rab5 activity and guanine exchange factor activity of ALS2. These findings indicate that vesicular ALS2, secreted in hypoxia, promotes endothelial cell events leading to angiogenesis. Finally, these events might explain how tumor angiogenesis proceeds in hypoxic conditions., (© 2024 Federation of American Societies for Experimental Biology.)

The etiology of the neurodegenerative disease amyotrophic lateral sclerosis (ALS) is complex and considered multifactorial. The majority of ALS cases are sporadic, but familial cases also exist. Estimates of heritability range from 8% to 61%, indicating that additional factors beyond genetics likely contribute to ALS. Numerous environmental factors are considered, which may add up and synergize throughout an individual's lifetime building its unique exposome. One level of integration between genetic and environmental factors is epigenetics, which results in alterations in gene expression without modification of the genome sequence. Methylation reactions, targeting DNA or histones, represent a large proportion of epigenetic regulations and strongly depend on the availability of methyl donors provided by the ubiquitous one-carbon (1C) metabolism. Thus, understanding the interplay between exposome, 1C metabolism, and epigenetic modifications will likely contribute to elucidating the mechanisms underlying altered gene expression related to ALS and to developing targeted therapeutic interventions. Here, we review evidence for 1C metabolism alterations and epigenetic methylation dysregulations in ALS, with a focus on the impairments reported in neural tissues, and discuss these environmentally driven mechanisms as the consequences of cumulative exposome or late environmental hits, but also as the possible result of early developmental defects.

Chemoresistance is a common problem in ovarian cancer (OvCa) treatment, where resistant cells, in response to chemotherapy, secrete small extracellular vesicles (sEVs), known as chemo-sEVs, that transfer resistance to recipient cells. sEVs are formed as intraluminal vesicles (ILVs) within multivesicular endosomes (MVEs), whose trafficking is regulated by Ras-associated binding (RAB) GTPases that mediate sEVs secretion or lysosomal degradation. A decrease in lysosomal function can promote sEVs secretion, but the relationship between MVEs trafficking pathways and sEVs secretion in OvCa chemoresistance is unclear. Here, we show that A2780cis cisplatin (CCDP) resistant OvCa cells had an increased number of MVEs and ILVs structures, higher levels of Endosomal Sorting Complex Required for Transport (ESCRTs) machinery components, and RAB27A compared to A2780 CDDP-sensitive OvCa cells. CDDP promoted the secretion of chemo-sEVs in A2780cis cells, enriched in DNA damage response proteins. A2780cis cells exhibited poor lysosomal function with reduced levels of RAB7, essential in MVEs-Lysosomal trafficking. The silencing of RAB27A in A2780cis cells prevents the Chemo-EVs secretion, reduces its chemoresistance and restores lysosomal function and levels of RAB7, switching them into an A2780-like cellular phenotype. Enhancing lysosomal function with rapamycin reduced chemo-sEVs secretion. Our results suggest that adjusting the balance between secretory MVEs and lysosomal MVEs trafficking could be a promising strategy for overcoming CDDP chemoresistance in OvCa., 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., (© 2024 The Author(s). Journal of Extracellular Biology published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

Situs inversus totalis (SIT) is a congenital condition in which the major visceral organs are reversed or in a mirror image from their normal positions that affects one per 10,000 live births. It is associated with dextrocardia (DXC) in which the heart is located on the right side of the chest. We present a challenging cardiac resynchronization therapy (CRT) implantation in a 60-year-old man with SIT-DXC, heart failure, extreme bradycardia, wide QRS, and left ventricular (LV) dysfunction. The procedure was complex due to the mirror-image anatomy and the tortuous origin of the coronary sinus (CS) branches that required a subselection catheter for adequate lead implantation., (© 2023 Wiley Periodicals LLC.)

Objectives: Lung metastases in adenoid cystic carcinoma (ACC) usually have indolent growth and the optimal timing to start systemic therapy is not established. We assessed ACC lung metastasis tumor growth dynamics and compared the prognostic value of time to progression (TTP) and tumor volume doubling time (TVDT)., Methods: The study included ACC patients with ≥1 pulmonary metastasis (≥5 mm) and at least 2 chest computed tomography scans. Radiology assessment was performed from the first scan showing metastasis until treatment initiation or death. Up to 5 lung nodules per patient were segmented for TVDT calculation. To assess tumor growth rate (TGR), the correlation coefficient (r) and coefficient of determination (R 2 ) were calculated for measured lung nodules. TTP was assessed per RECIST 1.1; TVDT was calculated using the Schwartz formula. Overall survival was analyzed using the Kaplan-Meier method., Results: The study included 75 patients. Sixty-seven patients (89%) had lung-only metastasis on first CT scan. The TGR was overall constant (median R 2  = 0.974). Median TTP and TVDT were 11.2 months and 7.5 months. Shorter TVDT (<6 months) was associated with poor overall survival (HR = 0.48; p = 0.037), but TTP was not associated with survival (HR = 1.02; p = 0.96). Cox regression showed that TVDT but not TTP significantly correlated with OS. TVDT calculated using estimated tumor volume correlated with TVDT obtained by segmentation., Conclusion: Most ACC lung metastases have a constant TGR. TVDT may be a better prognostic indicator than TTP in lung-metastatic ACC. TVDT can be estimated by single longitudinal measurement in clinical practice., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: EADL, LGS, ZY, FB, COH, MS, KAW, WL, EYH, AEN, CDF, SK, MG have no conflict of interest. RF reports the following: Paid consultant/advisory board member: Elevar Therapeutics, Prelude Therapeutics, Regeneron, Sanofi, Eisai, and Remix. Royalties: UpToDate. Recipient of funds given to MD Anderson Cancer Center Ayala, Merck, Genentech, Pfizer, Nanobiotix, EMD Serono, Viracta, Seagen, and ISA Therapeutics. KW reports consulting fees from BluPrint Oncology., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Medicine is a discipline based on and nurtured by scientific research and technological development. The use of health services supported by information technology is increasing worldwide, and Latin America is no exception. Factors such as needing more specialists in peripheral cities, large geographic areas, and socio-cultural aspects limit the possibility of receiving timely and quality medical care services. Information Technology (IT) for health purposes, such as e-health, is a cost-effective solution for equitable access to quality healthcare services and optimization of the rising associated costs. As an e-health service, telemedicine facilitates and mediates distance communication between the patient and medical staff. Even though Latin America is at the beginning of the development of telemedicine, it would have a relevant impact, given the geographic and socioeconomic conditions of the population in this part of the world. Drawing on the extended Unified Theory of Acceptance and Use of Technology (UTAUT2) theory, we developed a theoretical model to identify the latent factors influencing the public acceptance of telemedicine and examined their interrelationships. A survey questionnaire was designed and administered to 391 residents in Antofagasta, a mine region of Chile. After that, structural equation modeling was employed to analyze the survey data. The results reveal that the UTAUT2 factors' performance expectancy, social influence, and price value significantly impact the intention to use ( R 2 = 0.693). Additionally, the model presented a good fit. This study enriches the existing theoretical research on the acceptance of telemedicine services and offers insights into understanding and managing technology in the Chilean health sector., Competing Interests: 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., (© 2024 The Authors.)

In this study, we investigated the inter-organelle communication between the Golgi apparatus (GA) and mitochondria. Previous observations suggest that GA-derived vesicles containing phosphatidylinositol 4-phosphate (PI(4)P) play a role in mitochondrial fission, colocalizing with DRP1, a key protein in this process. However, the functions of these vesicles and potentially associated proteins remain unknown. GOLPH3, a PI(4)P-interacting GA protein, is elevated in various types of solid tumors, including breast cancer, yet its precise role is unclear. Interestingly, GOLPH3 levels influence mitochondrial mass by affecting cardiolipin synthesis, an exclusive mitochondrial lipid. However, the mechanism by which GOLPH3 influences mitochondria is not fully understood. Our live-cell imaging analysis showed GFP-GOLPH3 associating with PI(4)P vesicles colocalizing with YFP-DRP1 at mitochondrial fission sites. We tested the functional significance of these observations with GOLPH3 knockout in MDA-MB-231 cells of breast cancer, resulting in a fragmented mitochondrial network and reduced bioenergetic function, including decreased mitochondrial ATP production, mitochondrial membrane potential, and oxygen consumption. Our findings suggest a potential negative regulatory role for GOLPH3 in mitochondrial fission, impacting mitochondrial function and providing insights into GA-mitochondria communication.

Objective: Studies of Wnt variants-related to bone resorption in periodontitis are limited. The aim of this study was to establish the genotype and allele frequency of gene variants associated with the Wnt pathway in systemically healthy individuals with and without periodontitis (PD)., Materials and Methods: One hundred fifty-seven systemically healthy individuals were evaluated, 90 with PD and 67 without PD. Periodontal clinical indexes, serological and clinical indices of inflammation, and the following variants associated with the Wnt pathway: DKK, SOST, LRP5, and KREMEN were analyzed by high resolution melting and confirmed by Sanger sequencing., Results: In the PD-free group, 67.2% of the individuals presented the variant for DKKrs1896367 (p = 0.008) and 82.6% had the variant for KREMEN rs132274 (p = 0.016). The heterozygous variant for the DKK rs1896367 polymorphism was associated with the absence of PD and lower severity OR: 0.33 (CI95% 0.15-0.70) and OR: 0.24 (CI95% 0.11-0.53), respectively. Similarly, KREMEN rs132274 was the homozygous variant associated with the absence of PD (OR: 0.33 (CI95% 0.13-0.88)). On the contrary, 85.6% of individuals with PD presented a variant for DKK rs1896368 (p = 0.042), all suffering severe forms of periodontitis., Conclusion: The presence of DKKrs1896367 and KREMENrs132274 variants in individuals without PD suggests that these single nucleotide polymorphisms could be protective factors for bone loss in PD. A very interesting finding is that the DKKrs1896368 variant was found in a high percentage of severe cases, suggesting that the presence of this variant may be related to the severe bone loss observed in PD., (© 2024. The Author(s).)

Background: Predicting relapse and overall survival (OS) in early-stage non-small-cell lung cancer (NSCLC) patients remains challenging. Therefore, we hypothesized that detection of circulating tumor DNA (ctDNA) can identify patients with increased risk of relapse and that integrating radiological tumor volume measurement along with ctDNA detectability improves prediction of outcome., Patients and Methods: We analyzed 366 serial plasma samples from 85 patients who underwent surgical resections and assessed ctDNA using a next-generation sequencing liquid biopsy assay, and measured tumor volume using a computed tomography-based three-dimensional annotation., Results: Our results showed that patients with detectable ctDNA at baseline or after treatment and patients who did not clear ctDNA after treatment had a significantly worse clinical outcome. Integrating radiological analysis allowed the stratification in risk groups prognostic of clinical outcome as confirmed in an independent cohort of 32 patients., Conclusions: Our findings suggest ctDNA and radiological monitoring could be valuable tools for guiding follow-up care and treatment decisions for early-stage NSCLC patients., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: There is no standard method for assembling the femoral head onto the femoral stem during total hip arthroplasty (THA). This study aimed to measure and record dynamic 3-dimensional (3D) THA head-neck assembly loads from residents, fellows, and attending surgeons, for metal and ceramic femoral heads., Methods: An instrumented apparatus measured dynamic 3D forces applied through the femoral stem taper in vitro for 31 surgeons (11 attendings, 14 residents, 6 fellows) using their preferred technique (ie, number of hits or mallet strikes). Outcome variables included peak axial force, peak resultant force, impulse of the resultant force, loading rate of the resultant force, and off-axis angle. They were compared between femoral head material, surgeon experience level, and the number of hits per trial., Results: Average peak axial force was 6.92 ± 2.11kN for all surgeons. No significant differences were found between femoral head material. Attendings applied forces more "on-axis" as compared to both residents and fellows. Nine surgeons assembled the head with 1 hit, 3 with 2 hits, 14 with 3 hits, 2 with 4 hits, and 3 with ≥5 hits. The first hit of multihit trials was significantly lower than single-hit trials for all outcome measures except the off-axis angle. The last hit of multihit trials had a significantly lower impulse of resultant force than single-hit trials., Conclusion: Differences in applied 3D force-time curve dynamic characteristics were found between surgeon experience level and single and multihit trials. No significant differences were found between femoral head material., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: The objective is to describe the HLA allelic frequency in PsA and correlate it with demographic and clinical variables., Methods: Retrospective study of adult patients with a diagnosis of PsA (n=23) and healthy controls (n=46), all with a request for HLA-A, B, C, DR. Typing was performed using HLA-PCR/SSO LifeCodes and analyzed on the LUMINEX IS100/200 xMAP ® system. (Ethics/Code HMC2022-014)., Results: One hundred thirty-eight alleles were included from 69 individuals, 43,5% women, aged 44,5±16,5 years in patients with PsA, with a mean age of disease onset of 33.4±14 years. Only 9.5% had a high Body Mass Index and dyslipidemia was the most frequent comorbidity (34.8%), followed by high blood pressure (26,1%). 82% debuted with skin manifestation and once the joint disease was established, the predominance was peripheral (74%) due to arthritis/arthralgia in 74%, enthesitis in 30% and dactylitis in 13%. The allele frequencies were for HLA*A 2402 (13%), 3201 (13%) and 2427 (8,7%), for HLA*B 1402 (17,4%), 4002 (17,4%), 3801 (13%) and HLA*DR 0404 (17,4%), 0407 (13%). No HLA*B27 was identified and HLA*C0602 was only 2,2%. HLA A*0201 and DR*1301 were less frequent in controls versus PsA (p=0.024 and 0,029, respectively), while HLA*B1302 was frequent in PsA (p=0,035)., Conclusions: Curiously, there were no positive results for HLAB*27, which may be related to the population mix. HLA Cw6 is traditionally associated with psoriasis. However, its absence has been linked to nail disorders and PsA; consequently, in our study, it had a low frequency (2,2%). On the other hand, HLA*B1302 has been related to the disease and its early onset; in the healthy Colombian population, it has been described in 0,92%; in our group, it is found to be significant in patients without establishing a clinical association. Few previous studies report HLA results in PsA in Colombia.

Membrane vesicles (MVs) are envelope-derived extracellular sacs that perform a broad diversity of physiological functions in bacteria. While considerably studied in pathogenic microorganisms, the roles, relevance, and biotechnological potential of MVs from environmental bacteria are less well established. Acidithiobacillaceae family bacteria are active players in the sulfur and iron biogeochemical cycles in extremely acidic environments and drivers of the leaching of mineral ores contributing to acid rock/mine drainage (ARD/AMD) and industrial bioleaching. One key aspect of such a role is the ability of these bacteria to tightly interact with the mineral surfaces and extract electrons and nutrients to support their chemolithotrophic metabolism. Despite recent advances in the characterization of acidithiobacilli biofilms and extracellular matrix (ECM) components, our understanding of its architectural and mechanistic aspects remains scant. Using different microscopy techniques and nano-tracking analysis we show that vesiculation is a common phenomenon in distant members of the Acidithiobacillaceae family, and further explore the role of MVs in multicellular colonization behaviors using ' Fervidacidithiobacillus caldus ' as a bacterial model. Production of MVs in ' F. caldus ' occurred in both planktonic cultures and biofilms formed on sulfur surfaces, where MVs appeared individually or in chains resembling tube-shaped membranous structures (TSMSs) important for microbial communication. Liquid chromatography-mass spectrometry data and bioinformatic analysis of the MV-associated proteome revealed that ' F. caldus ' MVs were enriched in proteins involved in cell-cell and cell-surface processes and largely typified the MVs as outer MVs (OMVs). Finally, microbiological assays showed that amendment of ' F. caldus ' MVs to cells and/or biofilms affects collective colonizing behaviors relevant to the ecophysiology and applications of these acidophiles, providing grounds for their exploitation in biomining., 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. The handling editor AS declared a past co-authorship with the author MVe. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Rossoni, Beard, Segura-Bidermann, Duarte-Ramírez, Osorio, Varas-Godoy, Martínez-Bellange, Vera, Quatrini and Castro.)

Furunculosis, caused by Aeromonas salmonicida , poses a significant threat to both salmonid and non-salmonid fish in diverse aquatic environments. This study explores the genomic intricacies of re-emergent A. salmonicida outbreaks in Atlantic salmon ( Salmo salar ). Previous clinical cases have exhibited pathological characteristics, such as periorbital hemorrhages and gastrointestinal abnormalities. Genomic sequencing of three Chilean isolates (ASA04, ASA05, and CIBA&#95;5017) and 25 previously described genomes determined the pan-genome, phylogenomics, insertion sequences, and restriction-modification systems. Unique gene families have contributed to an improved understanding of the psychrophilic and mesophilic clades, while phylogenomic analysis has been used to identify mesophilic and psychrophilic strains, thereby further differentiating between typical and atypical psychrophilic isolates. Diverse insertion sequences and restriction-modification patterns have highlighted genomic structural differences, and virulence factor predictions can emphasize exotoxin disparities, especially between psychrophilic and mesophilic strains. Thus, a novel plasmid was characterized which emphasized the role of plasmids in virulence and antibiotic resistance. The analysis of antibiotic resistance factors revealed resistance against various drug classes in Chilean strains. Overall, this study elucidates the genomic dynamics of re-emergent A. salmonicida and provides novel insights into their virulence, antibiotic resistance, and population structure.

Maintaining the high overall health of farmed animals is a central tenant of their well-being and care. Intense animal crowding in aquaculture promotes animal morbidity especially in the absence of straightforward methods for monitoring their health. Here, we used bacterial 16S ribosomal RNA gene sequencing to measure bacterial population dynamics during P. salmonis infection. We observed a complex bacterial community consisting of a previously undescribed core pathobiome. Notably, we detected Aliivibrio wodanis and Tenacibaculum dicentrarchi on the skin ulcers of salmon infected with P. salmonis , while Vibrio spp. were enriched on infected gills. The prevalence of these co-occurring networks indicated that coinfection with other pathogens may enhance P. salmonis pathogenicity.

The symbolic analysis of heart rate variability (biomarker of cardiac autonomic homeostasis) is a nonlinear and effective tool for pattern extraction and classification in a series analysis, which implies the transformation of an original time series into symbols, represented by numbers. Autonomic heart rate control is influenced by different factors, and better indicators of heart rate variability are found in healthy young individuals than in older and sicker individuals. The aim of this study was to compare the indicators of heart rate variability among healthy dogs in different age groups and in health status using the nonlinear method of symbolic analysis to evaluate the diagnostic accuracy of this method for the risk of death in dogs. An increase in cardiac sympathetic modulation was observed in puppies and dogs at risk of death, which was evidenced by a marked increase of 0 V% (without variation - associated with sympathetic modulation) and a decrease in patterns of 2 V% (two variations - associated with parasympathetic modulation), while the opposite was observed in young adult dogs with increased parasympathetic modulation. Elderly dogs showed a gradual decrease in parasympathetic activity, which tended to worsen with loss of health. It is concluded that the variables of symbolic analysis may be useful to evaluate autonomic modulation in dogs and assist in the differentiation between health states, advanced disease and death throughout the life cycle and have been shown to be indices with high specificity, sensitivity and diagnostic accuracy to help identify dogs at risk of death.

The influenza A virus (IAV) poses a significant global threat to public health and food security. Particularly concerning is the avian influenza virus (AIV) subtype H5N1, which has spread from Europe to North and Central/South America. This review presents recent developments in IAV evolution in birds, mammals, and humans in Chile. Chile's encounter with IAV began in 2002, with the highly pathogenic avian influenza (HPAI) H7N3 virus, derived from a unique South American low pathogenic avian influenza (LPAI) virus. In 2016-2017, LPAI H7N6 caused outbreaks in turkey, linked to wild birds in Chile and Bolivia. The pandemic influenza A (H1N1) 2009 (H1N1pdm09) virus in 2009 decreased egg production in turkeys. Since 2012, diverse IAV subtypes have emerged in backyard poultry and pigs. Reassortant AIVs, incorporating genes from both North and South American isolates, have been found in wild birds since 2007. Notably, from December 2022, HPAI H5N1 was detected in wild birds, sea lions, and a human, along Chile's north coast. It was introduced through Atlantic migratory flyways from North America. These findings emphasize the need for enhanced biosecurity on poultry farms and ongoing genomic surveillance to understand and manage AIVs in both wild and domestic bird populations in Chile.

An unbalanced composition of gut microbiota in fish is hypothesized to play a role in promoting bacterial infections, but the synergistic or antagonistic interactions between bacterial groups in relation to fish health are not well understood. We report that pathogenic species in the Piscirickettsia, Aeromonas, Renibacterium and Tenacibaculum genera were all detected in the digesta and gut mucosa of healthy Atlantic salmon without clinical signs of disease. Although Piscirickettsia salmonis (and other pathogens) occurred in greater frequencies of fish with clinical Salmonid Rickettsial Septicemia (SRS), the relative abundance was about the same as that observed in healthy fish. Remarkably, the SRS-positive fish presented with a generalized mid-gut dysbiosis and positive growth associations between Piscirickettsiaceae and members of other taxonomic families containing known pathogens. The reconstruction of metabolic phenotypes based on the bacterial networks detected in the gut and mucosa indicated the synthesis of Gram-negative virulence factors such as colanic acid and O-antigen were over-represented in SRS positive fish. This evidence indicates that cooperative interactions between organisms of different taxonomic families within localized bacterial networks might promote an opportunity for P. salmonis to cause clinical SRS in the farm environment., (© 2023. Springer Nature Limited.)

Aims: Pneumonitis is a common and potentially deadly complication of combined chemoradiation and immune checkpoint inhibition (CRT-ICI) in patients with locally advanced non-small cell lung cancer (LA-NSCLC). In this study we sought to identify the risk factors for pneumonitis with CRT-ICI therapy in LA-NSCLC cases and determine its impact on survival., Materials and Methods: We conducted a retrospective chart review of 140 patients with LA-NSCLC who underwent curative-intent CRT-ICI with durvalumab between 2018 and 2021. Pneumonitis was diagnosed by a multidisciplinary team of clinical experts. We used multivariable cause-specific hazard models to identify risk factors associated with grade ≥2 pneumonitis. We constructed multivariable Cox proportional hazard models to investigate the impact of pneumonitis on all-cause mortality., Results: The median age of the cohort was 67 years; most patients were current or former smokers (86%). The cumulative incidence of grade ≥2 pneumonitis was 23%. Among survivors, 25/28 patients had persistent parenchymal scarring. In multivariable analyses, the mean lung dose (hazard ratio 1.14 per Gy, 95% confidence interval 1.03-1.25) and interstitial lung disease (hazard ratio 3.8, 95% confidence interval 1.3-11.0) increased the risk for pneumonitis. In adjusted models, grade ≥2 pneumonitis (hazard ratio 2.5, 95% confidence interval 1.0-6.2, P = 0.049) and high-grade (≥3) pneumonitis (hazard ratio 8.3, 95% confidence interval 3.0-23.0, P < 0.001) were associated with higher all-cause mortality., Conclusions: Risk factors for pneumonitis in LA-NSCLC patients undergoing CRT-ICI include the mean radiation dose to the lung and pre-treatment interstitial lung disease. Although most cases are not fatal, pneumonitis in this setting is associated with markedly increased mortality., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Elevated expression of CAV1 in breast cancer increases tumor progression. Extracellular vesicles (EVs) from CAV1-expressing MDA-MB-231 breast cancer cells contain Tenascin C (TNC), but the relevance of TNC remained to be defined. Methods: EVs were characterized by nanotracking analysis, microscopy and western blotting. The uptake of EVs by cells was studied using flow cytometry. The effects of EVs on breast cancer cells were tested in migration, invasion, colony formation and in vivo assays. Results: EVs were taken up by cells; however, only those containing TNC promoted invasiveness. In vivo , EVs lacking TNC ceased to promote tumor growth. Conclusion: CAV1 and TNC contained in breast cancer cell-derived EVs were identified as proteins that favor progression of breast cancer.

Background: Nitric oxide is produced by different nitric oxide synthases isoforms. NO activates two signaling pathways, one dependent on soluble guanylate cyclase and protein kinase G, and other where NO post-translationally modifies proteins through S-nitrosylation, which is the modification induced by NO in free-thiol cysteines in proteins to form S-nitrosothiols. High levels of NO have been detected in blood of breast cancer patients and increased NOS activity has been detected in invasive breast tumors compared to benign or normal breast tissue, suggesting a positive correlation between NO biosynthesis, degree of malignancy and metastasis. During metastasis, the endothelium plays a key role allowing the adhesion of tumor cells, which is the first step in the extravasation process leading to metastasis. This step shares similarities with leukocyte adhesion to the endothelium, and it is plausible that it may also share some regulatory elements. The vascular cell adhesion molecule-1 (VCAM-1) expressed on the endothelial cell surface promotes interactions between the endothelium and tumor cells, as well as leukocytes. Data show that breast tumor cells adhere to areas in the vasculature where NO production is increased, however, the mechanisms involved are unknown., Results: We report that the stimulation of endothelial cells with interleukin-8, and conditioned medium from breast tumor cells activates the S-nitrosylation pathway in the endothelium to induce leukocyte adhesion and tumor cell extravasation by a mechanism that involves an increased VCAM-1 cell surface expression in endothelial cells. We identified VCAM-1 as an S-nitrosylation target during this process. The inhibition of NO signaling and S-nitrosylation blocked the transmigration of tumor cells through endothelial monolayers. Using an in vivo model, the number of lung metastases was inhibited in the presence of the S-nitrosylation inhibitor N-acetylcysteine (NAC), which was correlated with lower levels of S-nitrosylated VCAM-1 in the metastases., Conclusions: S-Nitrosylation in the endothelium activates pathways that enhance VCAM-1 surface localization to promote binding of leukocytes and extravasation of tumor cells leading to metastasis. NAC is positioned as an important tool that might be tested as a co-therapy against breast cancer metastasis., (© 2023. Sociedad de Biologia de Chile.)

The family Profundulidae includes some one of the most enigmatic freshwater fishes of Mesoamerica: despite many attempts, a robust phylogenetic framework to delimit species is lacking, mainly due to limited morphological variation within the group. The accumulation of molecular data of profundulid fishes has led to advances in the description of new taxa, but relatively less progress has been made estimating evolutionary and phylogenetic relationships for this fish family. Here, we adopt an integrative taxonomy approach including the use of nuclear and mitochondrial DNA sequences, morphometric and ecological data, to test species boundaries in profundulid fishes in the westernmost area of their known distribution range in the states of Guerrero and Oaxaca, Mexico. Using a combination of methods for species discovery and validation based on Bayesian gene tree topologies, our analyses support the delimitation of 15 valid species of profundulid fishes - a combination of previously described species validated by this study, the synonymy of unsupported taxa, and the description of two new species. Using species delimitation methods, examination of phenotypic variation, and ecological niche characterization, we also identify five potentially new lineages which require further evidence to be erected as new species. We demonstrate that the use of an integrative taxonomy approach provides a robust methodology to delimit species in a taxonomically complex group like Profundulidae. Accurate taxonomic and ecological information is crucial for the conservation of these microendemic fishes, as several species are endangered., 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 © 2023 Elsevier Inc. All rights reserved.)

The "timed inspiratory effort" (TIE) index, a new predictor of weaning outcome, normalizes the maximal inspiratory pressure with the time required to reach this value up to 60 s, incorporating the time domain into the assessment of inspiratory muscle function. The objective of this study was to determine whether the TIE predicts successful extubation at a similar rate as the T-piece trial with less time required. A non-inferiority randomized controlled trial was performed with ICU subjects eligible for weaning. The participants were allocated to the TIE or the T-piece groups. The primary outcome was successful weaning, and the main secondary outcome was ICU mortality. Eighty participants of each group were included in the final analysis. Time from the start of a successful test to effective extubation was significantly lower in the TIE group than in the T-piece group, 15 (10 to 24) vs 55 (40 to 75) min, P<0.001. In the Kaplan-Meier analysis, no significant differences were found in successful weaning (79.5 vs 82.5%, P=0.268) or survival rate (62.9 vs 53.8%, P=0.210) between the TIE and T-piece groups at the 30th day. In this preliminary study, the TIE index was not inferior to the T-piece trial as a decision-making tool for extubation and allowed a reduction in the decision time.

Microglia are the brain-resident immune cells responsible for surveilling and protecting the central nervous system. These cells can express a wide array of immune genes, and that expression can become highly dynamic in response to changes in the environment, such as traumatic injury or neurological disease. Though microglial immune responses are well studied, we still do not know many mechanisms and regulators underlying all the varied microglial responses. Serpin E2 is a serine protease inhibitor that acts on a wide variety of serine proteases, with particularly potent affinity for the blood clotting enzyme thrombin. In the brain, Serpin E2 is highly expressed by many cell types, especially glia, and loss of Serpin E2 leads to behavioral changes as well as deficits in synaptic plasticity. To determine whether Serpin E2 is important for maintaining homeostasis in glia, we performed RNA sequencing of microglia and astrocytes from Serpin E2-deficient mice in a healthy state or under immune activation due to lipopolysaccharide (LPS) injection. We found that microglia in Serpin E2-deficient mice had higher expression of antimicrobial genes, while astrocytes did not display any robust changes in transcription. Furthermore, the lack of Serpin E2 did not affect transcriptional responses to LPS in either microglia or astrocytes. Overall, we find that Serpin E2 is a regulator of antimicrobial genes in microglia., 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 © 2023 Elsevier B.V. All rights reserved.)

Nitrogen (N) doped graphene materials have been synthesized using the sole precursor adenine on the Ir(111) and Ru(0001) surfaces. X-ray photoelectron spectroscopy and scanning tunneling microscopy (STM) have been used to characterize the obtained N-doped graphene materials. Several graphitic and pyridinic N dopants have been identified on the atomic scale by combining STM measurements and STM simulations based on density functional theory calculations., (Creative Commons Attribution license.)

Gallbladder cancer (GBC) is commonly diagnosed at late stages when conventional treatments achieve only modest clinical benefit. Therefore, effective treatments for advanced GBC are needed. In this context, the administration of T cells genetically engineered with chimeric antigen receptors (CAR) has shown remarkable results in hematological cancers and is being extensively studied for solid tumors. Interestingly, GBC tumors express canonical tumor-associated antigens, including the carcinoembryonic antigen (CEA). However, the potential of CEA as a relevant antigen in GBC to be targeted by CAR-T cell-based immunotherapy has not been addressed. Here we show that CEA was expressed in 88% of GBC tumors, with higher levels associated with advanced disease stages. CAR-T cells specifically recognized plate-bound CEA as evidenced by up-regulation of 4-1BB, CD69 and PD-1, and production of effector cytokines IFN-γ and TNF-α. In addition, CD8 + CAR-T cells up-regulated the cytotoxic molecules granzyme B and perforin. Interestingly, CAR-T cell activation occurred even in the presence of PD-L1. Consistent with these results, CAR-T cells efficiently recognized GBC cell lines expressing CEA and PD-L1, but not a CEA-negative cell line. Furthermore, CAR-T cells exhibited in vitro cytotoxicity and reduced in vivo tumor growth of GB-d1 cells. In summary, we demonstrate that CEA represents a relevant antigen for GBC that can be targeted by CAR-T cells at the preclinical level. This study warrants further development of the adoptive transfer of CEA-specific CAR-T cells as a potential immunotherapy for GBC., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Purpose: We conducted a phase II trial evaluating the efficacy of VEGFR inhibitor axitinib and PD-L1 inhibitor avelumab in patients with recurrent/metastatic adenoid cystic carcinoma (R/M ACC)., Patients and Methods: Eligible patients had R/M ACC with progression within 6 months before enrollment. Treatment consisted of axitinib and avelumab. The primary end point was objective response rate (ORR) per RECIST 1.1; secondary end points included progression-free survival (PFS), overall survival (OS), and toxicity. Simon's optimal two-stage design tested the null hypothesis of ORR ≤5% versus ORR ≥20% at 6 months; ≥4 responses in 29 patients would reject the null hypothesis., Results: Forty patients enrolled from July 2019 to June 2021; 28 were evaluable for efficacy (six screen failures; six evaluable for safety only). The confirmed ORR was 18% (95% CI, 6.1 to 36.9); there was one unconfirmed partial response (PR). Two patients achieved PR after 6 months; thus, the ORR at 6 months was 14%. The median follow-up time for surviving patients was 22 months (95% CI, 16.6 to 39.1 months). The median PFS was 7.3 months (95% CI, 3.7 to 11.2 months), 6-month PFS rate was 57% (95% CI, 41 to 78), and median OS was 16.6 months (95% CI, 12.4 to not reached months). Most common treatment-related adverse events (TRAEs) included fatigue (62%), hypertension (32%), and diarrhea (32%). Ten (29%) patients had serious TRAEs, all grade 3; four patients (12%) discontinued avelumab, and nine patients (26%) underwent axitinib dose reduction., Conclusion: The study reached its primary end point with ≥4 PRs in 28 evaluable patients (confirmed ORR of 18%). The potential added benefit of avelumab to axitinib in ACC requires further investigation.

Nutritional immunity regulates the homeostasis of micronutrients such as iron, manganese, and zinc at the systemic and cellular levels, preventing the invading microorganisms from gaining access and thereby limiting their growth. Therefore, the objective of this study was to evaluate the activation of nutritional immunity in specimens of Atlantic salmon ( Salmo salar ) that are intraperitoneally stimulated with both live and inactivated Piscirickettsia salmonis . The study used liver tissue and blood/plasma samples on days 3, 7, and 14 post-injections (dpi) for the analysis. Genetic material (DNA) of P. salmonis was detected in the liver tissue of fish stimulated with both live and inactivated P. salmonis at 14 dpi. Additionally, the hematocrit percentage decreased at 3 and 7 dpi in fish stimulated with live P. salmonis , unchanged in fish challenged with inactivated P. salmonis . On the other hand, plasma iron content decreased during the experimental course in fish stimulated with both live and inactivated P. salmonis , although this decrease was statistically significant only at 3 dpi. Regarding the immune-nutritional markers such as tfr1 , dmt1 , and ireg1 were modulated in the two experimental conditions, compared to zip8 , ft-h , and hamp , which were down-regulated in fish stimulated with live and inactivated P. salmonis during the course experimental. Finally, the intracellular iron content in the liver increased at 7 and 14 dpi in fish stimulated with live and inactivated P. salmonis , while the zinc content decreased at 14 dpi under both experimental conditions. However, stimulation with live and inactivated P. salmonis did not alter the manganese content in the fish. The results suggest that nutritional immunity does not distinguish between live and inactivated P. salmonis and elicits a similar immune response. Probably, this immune mechanism would be self-activated with the detection of PAMPs, instead of a sequestration and/or competition of micronutrients by the living microorganism., 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 © 2023 Martínez, Oyarzún-Salazar, Quilapi, Coronado, Enriquez, Vargas-Lagos, Oliver, Santibañez, Godoy, Muñoz, Vargas-Chacoff and Romero.)

In this work, we have studied the Ising model with one- and two-spin flip competing dynamics on a two-dimensional additive small-world network (A-SWN). The system model consists of an L×L square lattice where each site of the lattice is occupied by a spin variable that interacts with the nearest-neighbor spins and it has a certain probability p of being additionally connected at random to one of its farther neighbors. The dynamics present in the system can be defined by the probability q of being in contact with a heat bath at a given temperature T and, at the same time, with a probability of (1-q) the system is subjected to an external flux of energy into the system. The contact with the heat bath is simulated by one-spin flip according to the Metropolis prescription, while the input of energy is mimicked by the two-spin flip process, involving a simultaneous flipping of a pair of neighboring spins. We have employed Monte Carlo simulations to obtain the thermodynamic quantities of the system, such as the total m&#95;{L}^{F} and staggered m&#95;{L}^{AF} magnetizations per spin, the susceptibility χ&#95;{L}, and the reduced fourth-order Binder cumulant U&#95;{L}. We have built the phase diagram for the stationary states of the model in the plane T versus q, showing the existence of two continuous transition lines for each value of p: one line between the ferromagnetic F and paramagnetic P phases and the other line between the P and antiferromagnetic AF phases. Therefore, we have shown that the phase diagram topology changes when p increases. Using the finite-size scaling analysis, we also obtained the critical exponents for the system, where, varying the parameter p, we have observed a different universality class from the Ising model in the regular square lattice to the A-SWN.

The genus Gyrodactylus von Nordmann, 1832 is one of the most diverse within the class Monogenea; it contains mainly parasites of freshwater and marine teleost fishes. Around 40 species of Gyrodactylus have been described from gobiid fishes; mainly in Europe, as only two species are known from the Americas. In this study, we describe three new gyrodactylids from the body surface and fins of the goby Sicydium salvini (Gobiidae, Sycydiinae), which has a wide distribution on the Pacific coast, from Mexico to Panama. We describe Gyrodactylus oaxacae n. sp., G. atoyacensis n. sp. and G. salvini n. sp. collected from rivers draining to the eastern Pacific in the state of Oaxaca, Mexico. Morphologically, G. atoyacensis n. sp. and G. salvini n. sp. are very similar, and both are easily differentiated from G. oaxacae n. sp. Phylogenetic hypotheses based on sequences of the Internal Transcribed Spacers (ITS1-5.8S-ITS2 rDNA) and the D2 + D3 domains of the large ribosomal subunit (28S rDNA) support the erection of the three new taxa; and suggest that G. atoyacensis n. sp. and G. salvini n. sp. are sister species. These gyrodactylids are the first monogeneans described from gobies of the genus Sicydium in Mexico., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

We describe two new species of monogenean parasites of the genus Gyrodactylus von Nordmann, 1832 infecting Neotropical catfishes (Siluriformes) in southern Mexico: Gyrodactylus chulini n. sp. from 'chulín', Rhamdia laticauda collected in Oaxaca; and Gyrodactylus juili n. sp. from 'juil', Rhamdia guatemalensis from Veracruz. Morphologically, both new taxa are similar to Gyrodactylus spp. infecting catfishes (Siluriformes) in South America. Sequences of the internal transcribed spacers (ITS1-5.8S-ITS2 rDNA), the D2+D3 domains of the large ribosomal subunit (28S rDNA) and the cytochrome oxidase II (COII) gene were obtained from multiple parasite specimens and analysed using Bayesian inference. Phylogenetic hypotheses using ITS rDNA and COII genes, recovered two new Gyrodactylus species from Rhamdia spp.: G. chulini n. sp.; and Gyrodactylus juili n. sp., which are sister species to Gyrodactylus lilianae , a parasite of Rhamdia quelen in Brazil, and show strong affinity to other gyrodactytlids infecting Neotropical catfishes. This suggests that these new taxa, the first gyrodactylids described from Rhamdia spp. in Mexico, co-migrated to Tropical Middle America with their Neotropical catfish hosts, after the emergence of the Isthmus of Panama.

Glioblastoma (GBM) is the most common and aggressive type of brain tumor due to its elevated recurrence following treatments. This is mainly mediated by a subpopulation of cells with stemness traits termed glioblastoma stem-like cells (GSCs), which are extremely resistant to anti-neoplastic drugs. Thus, an advancement in the understanding of the molecular processes underlying GSC occurrence should contribute significantly towards progress in reducing aggressiveness. High levels of endothelin-converting enzyme-1 (ECE1), key for endothelin-1 (ET-1) peptide activation, have been linked to the malignant progression of GBM. There are four known isoforms of ECE1 that activate ET-1, which only differ in their cytoplasmic N-terminal sequences. Isoform ECE1c is phosphorylated at Ser-18 and Ser-20 by protein kinase CK2, which increases its stability and hence promotes aggressiveness traits in colon cancer cells. In order to study whether ECE1c exerts a malignant effect in GBM, we designed an ECE1c mutant by switching a putative ubiquitination lysine proximal to the phospho-serines Lys-6-to-Arg (i.e., K6R). This ECE1c K6R mutant was stably expressed in U87MG, T98G, and U251 GBM cells, and their behavior was compared to either mock or wild-type ECE1c-expressing clone cells. ECE1c K6R behaved as a highly stable protein in all cell lines, and its expression promoted self-renewal and the enrichment of a stem-like population characterized by enhanced neurospheroid formation, as well as increased expression of stem-like surface markers. These ECE1c K6R -derived GSC-like cells also displayed enhanced resistance to the GBM-related chemotherapy drugs temozolomide and gemcitabine and increased expression of the ABCG2 efflux pump. In addition, ECE1c K6R cells displayed enhanced metastasis-associated traits, such as the modulation of adhesion and the enhancement of cell migration and invasion. In conclusion, the acquisition of a GSC-like phenotype, together with heightened chemoresistance and invasiveness traits, allows us to suggest phospho-ECE1c as a novel marker for poor prognosis as well as a potential therapeutic target for GBM.

Pathogen inactivation for platelets by riboflavin system (MIRASOL) efficiently reduces transfusion related pathogen transmission. However little is known about its impact on platelets' immunomodulatory biochemical profile. We aimed was to assess the effects of MIRASOL treatment on platelet quality parameters and immunomodulatory molecules CD62P, RANTES, and CD40L in Single Donor Platelets (SDPs) resuspended in plasma (SDP-P) or T-PAS and additive solution (SDP-A). Twenty nine SDPs (15 SDP-P and 14 SDP-A) were included in the study. Samples were collected before, after MIRASOL treatment and just before transfusion. P-selectin (CD62P), RANTES, and CD40L were tested by ELISA. Platelet products quality assays were also performed. Platelet count/unit decreased after Mirasol treatment by 13 %. The pH of all units decreased over the 5-day storage period but remained above expected limits and the swirling test was positive throughout storage. P-selectin levels were not different between the three different time points in both SDPs-P and SDPs-A while RANTES levels were found to differ statistically significantly at the three different time points in all units and in the SPD-A subgroup. CD40L levels in all SDP products increased slightly during storage but this was not statistically significant. CD62P, RANTES, and CD40L in all time points were elevated in SDPs-A compared to SDPs-P but not at a statistically significant level. In conclusion MIRASOL treatment apart from RANTES increase does not seem to substantially affect platelets associated other cytokines and immunomodulatory molecules namely P-selectin and sCD40L which are implicated in immune transfusion reactions., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Recent rises in incident tuberculosis (TB) cases in Paraguay and the increasing concentration of TB within prisons highlight the urgency of targeting strategies to interrupt transmission and prevent new infections. However, whether specific cities or carceral institutions play a disproportionate role in transmission remains unknown. We conducted prospective genomic surveillance, sequencing 471 Mycobacterium tuberculosis complex genomes, from inside and outside prisons in Paraguay's two largest urban areas, Asunción and Ciudad del Este, from 2016 to 2021. We found genomic evidence of frequent recent transmission within prisons and transmission linkages spanning prisons and surrounding populations. We identified a signal of frequent M. tuberculosis spread between urban areas and marked recent population size expansion of the three largest genomic transmission clusters. Together, our findings highlight the urgency of strengthening TB control programs to reduce transmission risk within prisons in Paraguay, where incidence was 70 times that outside prisons in 2021., (© 2023. The Author(s).)

A 28-day randomized open-label multicenter study was conducted to assess the efficacy of bromhexine plus standard of care (SOC) (n = 98) vs. SOC alone (n = 93) in 191 outpatients with mild-to-moderate COVID-19 in the primary health care setting. Bromhexine three daily doses of 10 mL (48 mg/day) were administered for seven days. The primary efficacy endpoint was the reduction of viral load estimated as the cycle thresholds (Ct) to detect ORF1ab, N Protein, and S Protein genes by RT-qPCR in saliva samples on day 4 as compared with baseline. Ct values of the three genes increased from baseline throughout days 4 to 14 (p < 0.001) but significant differences between the study groups were not found. Differences in the percentages of patients with low, medium, and high viral loads at 4, 7, and 14 days were not found either. In summary, treatment with bromhexine plus SCO was associated with a viral load reduction of ORF1ab, N Protein, and S Protein genes at day 4, which was not significantly different than similar viral load reductions observed with SOC alone. The present findings do not seem to favor the use of bromhexine as an antiviral in patients with COVID-19.

Most of the available knowledge in the literature on Mexican fishes and their parasites refers to information within political divisions and/or hydrological basins in the country. Indeed, only a few studies have analyzed the helminth fauna of these vertebrates as a biological group distributed nation-wide. This lack of available knowledge prevents the study of several basic and applied aspects involving fish-parasite interactions at different spatial and temporal scales. In this dataset, we compiled all the available geographic information on fish-helminth parasite interactions involving native and exotic fish species recorded in continental waters throughout the Mexican territory. After an exhaustive filtering and the curation of information, our data set contains 5999 records of 361 freshwater fish species (roughly 70% of known freshwater fish species occurring in Mexico) and 483 endo- and ectoparasitic helminths collected over an 85-year period (from 1936-2021) in 1070 localities distributed throughout Mexico. These records are mainly concentrated in only a few states located to the south and east of the country; although all states have been sampled and all major basins in Mexico are represented. The fish order with the highest number of records was Perciformes (n = 2325, 38.75%) while the fish family with the highest number of records was Cichlidae (n = 1741, 29.02%). Native species of fishes corresponded to 92.14% of the records (n = 5528) and fish-associated parasites were found in 41 habitat types in/on their host bodies. Regarding fish parasites, we found that most of the records are from the phylum Platyhelminthes (n = 4495, 74.92%). At the class level, we observed that Trematoda reached the highest number of records (n = 2965, 49.42%). Moreover, we found that Diplostomidae (n = 917, 15.25%) were the family of trematodes with the highest number of records. Most parasites were registered in their adult stage (n = 3730, 62.17%), followed by larval stages (n = 2267, 37.78%). We hope that the fish-parasite interactions data set will encourage researchers worldwide to explore different ecological and coevolutionary aspects of fishes and their helminth parasites, as well as provide useful information for the better implementation of conservation initiatives. There are no copyright restrictions; please cite this data paper when using its data in publications or teaching events., (© 2022 The Ecological Society of America.)

Infectious pancreatic necrosis (IPN), caused by IPNV, affects several species of farmed fish, particularly Atlantic salmon, and is responsible for significant economic losses in salmon aquaculture globally. Despite the introduction of genetically resistant farmed Atlantic salmon and vaccination strategies in the Chilean salmon industry since 2019, the number of IPN outbreaks has been increasing in farmed Atlantic salmon in the freshwater phase. This study examined gross and histopathological lesions of IPNV-affected fish, as well as the IPNV nucleotide sequence encoding the VP2 protein in clinical cases. The mortality reached 0.4% per day, and the cumulative mortality was from 0.4 to 3.5%. IPNV was isolated in the CHSE-214 cell line and was confirmed by RT-PCR, and VP2 sequence analysis. The analyzed viruses belong to IPNV genotype 5 and have 11 mutations in their VP2 protein. This is the first report of IPN outbreaks in farmed Atlantic salmon genetically resistant to IPNV in Chile. Similar outbreaks were previously reported in Scotland and Norway during 2018 and 2019, respectively. This study highlights the importance of maintaining a comprehensive surveillance program in conjunction with the use of farmed Atlantic salmon genetically resistant to IPNV.

Objectives: Neoadjuvant therapy has been theorized to increase complexity of non-small cell lung cancer resections; however, specific factors that contribute to intraoperative challenges after induction therapy have not been well described. We aimed to characterize the effect of nodal involvement and nodal treatment response on surgical complexity after neoadjuvant therapy., Methods: We identified patients treated with neoadjuvant therapy followed by anatomic lung resection for cN + non-small cell lung cancer between 2010 and 2020. Patients were categorized according to clinical N1 versus N2 disease. To evaluate the effect of nodal response to therapy, thoracic radiologists measured clinically suspected and pathologically involved lymph nodes before and after induction therapy. Operative reports were reviewed to identify technical challenges specifically related to nodal disease. Categorical outcomes were compared using Fisher exact test., Results: One hundred twenty-four patients met inclusion criteria, among whom 107 (86.3%) were treated with neoadjuvant chemotherapy, whereas chemoradiation (n = 8) and targeted therapy (n = 9) were less common. In cases with N1 disease, 8/38 (21.0%) required proximal pulmonary arterial control, whereas this was necessary in only 2/88 (2.3%) of N2 cases ( P  = .001). Likewise, sleeve resection and arterioplasty were needed more frequently during resection of N1 disease (7/38, 18.4%) versus N2 disease (0/88, P  < .001). Increased nodal response to therapy was associated with greater likelihood of requiring change in vascular approach ( P  = .011)., Conclusions: After induction therapy, N1 disease was associated with greater need for complex surgical maneuvers than N2 disease. Likewise, substantial treatment response was associated with increased intraoperative technical challenges. Recognizing such factors enables surgical teams to engage in appropriate operative planning to ensure patient safety., (© 2022 The Author(s).)

Background: The presence of Antinuclear antibodies/Dense Fine Speckled 70 (ANA/DFS70) has been proposed as a negative biomarker in the process of exclusion of systemic autoimmune/autoinflammatory rheumatic diseases (SARD). The purpose was to evaluate and characterize ANA/DFS70 patients in a large Colombian population with SARD; rheumatoid arthritis (RA), Psoriasis (PsO), Undifferentiated connective tissue disease (UCTD), first-degree relatives of (FDR), and healthy controls (HC)., Methods: ANA determination was performed using indirect immunofluorescence. Samples with positive dense fine granular staining in the nucleoplasm of the interphase cell (AC2) fluorescence were confirmed with CytoBead/ANA and ANA/modified (Knocked out for the PSPI1 gen)., Results: 530 mestizo Colombian participants were included. ANA/DFS70 antibody positivity in the whole group was 2.3%, and 0.8% in SARD; no RA patients were positive. ANA/DFS70 positives in UCTD were three women; the average time of evolution of the disease was 9.4 years. The most frequent clinical findings were arthralgias, non-erosive arthritis, and Raynaud's phenomenon. The PsO positive was a woman with C-reactive protein (CRP) positivity and a negative erythrocyte sedimentation rate (ESR) without any other positive autoantibody or extracutaneous manifestation. FDR and HC positives were 7/8 women. All were negative for other autoantibodies., Conclusions: ANA/DFS70 autoantibodies were present in Colombian patients with SARD at a shallow frequency, they were more prevalent in healthy individuals.

Amyotrophic lateral sclerosis (ALS) involves progressive motor neuron loss, leading to paralysis and death typically within 3-5 years of diagnosis. Dysfunctional astrocytes may contribute to disease and glial cell line-derived neurotrophic factor (GDNF) can be protective. Here we show that human neural progenitor cells transduced with GDNF (CNS10-NPC-GDNF) differentiated to astrocytes protected spinal motor neurons and were safe in animal models. CNS10-NPC-GDNF were transplanted unilaterally into the lumbar spinal cord of 18 ALS participants in a phase 1/2a study (NCT02943850). The primary endpoint of safety at 1 year was met, with no negative effect of the transplant on motor function in the treated leg compared with the untreated leg. Tissue analysis of 13 participants who died of disease progression showed graft survival and GDNF production. Benign neuromas near delivery sites were common incidental findings at post-mortem. This study shows that one administration of engineered neural progenitors can provide new support cells and GDNF delivery to the ALS patient spinal cord for up to 42 months post-transplantation., (© 2022. The Author(s).)