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Owen L Woodman,1 Jacinta M Ortega,1 Joanne L Hart,1 Thomas Klein,2 Simon Potocnik11School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia; 2Department of Cardiometabolic Diseases Research, Boehringer Ingelheim Pharma, Biberach, GermanyCorrespondence: Owen L WoodmanBaker Heart & Diabetes Institute, PO Box 6492, Melbourne 3004, AustraliaTel +61 38 532 1917Email owen.woodman@baker.edu.auPurpose: The aim of this study was to investigate the effects of the type-4 dipeptidyl peptidase (DPP-4) inhibitors linagliptin and vildagliptin as well as the sulfonylurea glimepiride on endothelium-dependent relaxation of aortae from female db/db mice with established hyperglycemia to determine whether these treatments were able to attenuate diabetes-induced endothelial dysfunction.Materials and methods: The mice were treated with glimepiride (2 mg/kg po per day, weeks 1–6, n=12), glimepiride plus vildagliptin (glimepiride 2 mg/kg po per day, weeks 1–6; vildagliptin 3 mg/kg po per day, weeks 4–6, n=11), glimepiride plus linagliptin (glimepiride 2 mg/kg po per day, weeks 1–6; linagliptin 3 mg/kg po per day, weeks 4–6, n=11) or linagliptin (3 mg/kg po per day, weeks 1–6, n=12). Endothelium-dependent relaxation using acetylcholine was assessed in the absence and presence of pharmacological tools (TRAM-34 1 μM; apamin 1 μM; N-nitro-L-arginine [L-NNA] 100 μM; 1H-[1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one [ODQ] 10 μM) to distinguish relaxation mediated by nitric oxide (NO).Results: Linagliptin was associated with a significant improvement in endothelium-dependent relaxation (ACh Rmax; db/db 41±1%, linagliptin 73±6%, p

Radiation dose and image quality in radiology are influenced by the X-ray prime factors: KVp, mAs, and source-detector distance. These parameters are set by the X-ray technician prior to the acquisition considering the radiographic position. A wrong setting of these parameters may result in exposure errors, forcing the test to be repeated with the increase of the radiation dose delivered to the patient. This work presents a novel approach based on deep learning that automatically estimates the radiographic position from a photograph captured prior to X-ray exposure, which can then be used to select the optimal prime factors. We created a database using 66 radiographic positions commonly used in clinical settings, prospectively obtained during 2022 from 75 volunteers in two different X-ray facilities. The architecture for radiographic position classification was a lightweight version of ConvNeXt trained with fine-tuning, discriminative learning rates, and a one-cycle policy scheduler. Our resulting model achieved an accuracy of 93.17% for radiographic position classification and increased to 95.58% when considering the correct selection of prime factors, since half of the errors involved positions with the same KVp and mAs values. Most errors occurred for radiographic positions with similar patient pose in the photograph. Results suggest the feasibility of the method to facilitate the acquisition workflow reducing the occurrence of exposure errors while preventing unnecessary radiation dose delivered to patients., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

T-cell activation is central for the initiation of T cell mediated adaptive immune response and is the result of the close communication between the Antigen Presenting Cell (APC) and the T lymphocyte. Although T-cell activation is currently well understood, and many intracellular pathways are well characterized, nevertheless new players are constantly identified, and this complements the known protein interactome. In this work we aimed to identify new proteins involved in T cell activation. We reviewed and analyzed results of microarray gene expression datasets reported in the public database GEO-NCBI. Using data from GSE136625, GSE50971, GSE13887, GSE11989 and GSE902 we performed different comparisons using R and other bioinformatic tools including GEO2R and we report here upregulated genes that have no previous reports in immune related functions and with potential participation upon T-cell activation. Our results indicate that RND3, SYT10, IgSF6 and PIN1 are potential new T-cell activation molecules., (© 2024. The Author(s).)

Alternative Splicing (AS) is an essential mechanism for eukaryotes. However, the consequences of deleting a single exon can be dramatic for the organism and can lead to cancer in humans. Additionally, alternative 5' and 3' splice sites, which define the boundaries of exons, also play key roles to human disorders. Therefore, Investigating AS events is crucial for understanding the molecular basis of human diseases and developing therapeutic strategies. Workflow for AS event analysis can be sampling followed by data analysis with bioinformatics to identify the different AS events in the control and case samples, data visualization for curation, and selection of relevant targets for experimental validation. The raw output of the analysis software does not favor the inspection of events by bioinformaticians requiring custom scripts for data visualization. In this work, we propose the Geneapp application with three modules: GeneappScript, GeneappServer, and GeneappExplorer. GeneappScript is a wrapper that assists in identifying AS in samples compared in two different approaches, while GeneappServer integrates data from AS analysis already performed by the user. In GeneappExplorer, the user visualizes the previous dataset by exploring AS events in genes with functional annotation. This targeted screens that Geneapp allows to perform helps in the identification of targets for experimental validation to confirm the hypotheses under study. The Geneapp is freely available for non-commercial use at https://geneapp.net to advance research on AS for bioinformatics., 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.)

Despite presenting a worse prognosis and being associated with highly aggressive tumors, triple-negative breast cancer (TNBC) is characterized by the higher frequency of tumor-infiltrating lymphocytes, which have been implicated in better overall survival and response to therapy. Though recent studies have reported the capacity of B lymphocytes to recognize overly-expressed normal proteins, and tumor-associated antigens, how tumor development potentially modifies B cell response is yet to be elucidated. Our findings reveal distinct effects of 4T1 and E0771 murine tumor development on B cells in secondary lymphoid organs. Notably, we observe a significant expansion of total B cells and plasma cells in the tumor-draining lymph nodes (tDLNs) as early as 7 days after tumor challenge in both murine models, whereas changes in the spleen are less pronounced. Surprisingly, within the tumor microenvironment (TME) of both models, we detect distinct B cell subpopulations, but tumor development does not appear to cause major alterations in their frequency over time. Furthermore, our investigation into B cell regulatory phenotypes highlights that the B10 Breg phenotype remains unaffected in the evaluated tissues. Most importantly, we identified an increase in CD19 + LAG-3 + cells in tDLNs of both murine models. Interestingly, although CD19 + LAG-3 + cells represent a minor subset of total B cells (< 3%) in all evaluated tissues, most of these cells exhibit elevated expression of IgD, suggesting that LAG-3 may serve as an activation marker for B cells. Corroborating with these findings, we detected distinct cell cycle and proliferation genes alongside LAG-3 analyzing scRNA-Seq data from a cohort of TNBC patients. More importantly, our study suggests that the presence of LAG-3 B cells in breast tumors could be associated with a good prognosis, as patients with higher levels of LAG-3 B cell transcripts had a longer progression-free interval (PFI). This novel insight could pave the way for targeted therapies that harness the unique properties of LAG-3 + B cells, potentially offering new avenues for improving patient outcomes in TNBC. Further research is warranted to unravel the mechanistic pathways of these cells and to validate their prognostic value in larger, diverse patient cohorts., (© 2024. The Author(s).)

This study examines the potential for widespread solar photovoltaic panel production in Mexico and emphasizes the country's unique qualities that position it as a strong manufacturing candidate in this field. An advanced model based on artificial neural networks has been developed to predict solar photovoltaic panel plant metrics. This model integrates a state-of-the-art non-linear programming framework using Pyomo as well as an innovative optimization and machine learning toolkit library. This approach creates surrogate models for individual photovoltaic plants including production timelines. While this research, conducted through extensive simulations and meticulous computations, unveiled that Latin America has been significantly underrepresented in the production of silicon, wafers, cells, and modules within the global market; it also demonstrates the substantial potential of scaling up photovoltaic panel production in Mexico, leading to significant economic, social, and environmental benefits. By hyperparameter optimization, an outstanding and competitive artificial neural network model has been developed with a coefficient of determination values above 0.99 for all output variables. It has been found that water and energy consumption during PV panel production is remarkable. However, water consumption (33.16 × 10 -4  m 3 /kWh) and the emissions generated (1.12 × 10 -6 TonCO 2 /kWh) during energy production are significantly lower than those of conventional power plants. Notably, the results highlight a positive economic trend, with module production plants generating the highest profits (35.7%) among all production stages, while polycrystalline silicon production plants yield comparatively lower earnings (13.0%). Furthermore, this study underscores a critical factor in the photovoltaic panel production process which is that cell production plants contribute the most to energy consumption (39.7%) due to their intricate multi-stage processes. The blending of Machine Learning and optimization models heralds a new era in resource allocation for a more sustainable renewable energy sector, offering a brighter, greener future., 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.)

Proteinuria is the main predictor of kidney graft loss. However, there is little information regarding the consequences of nephrotic proteinuria (NP) and nephrotic syndrome (NS) after a kidney transplant. We aimed to describe the clinical and histopathological characteristics of kidney recipients with nephrotic-range proteinuria and compare the graft surveillance between those who developed NS and those who did not. A total of 204 patients (18.6% of kidney transplants in the study period) developed NP, and 68.1% of them had NS. Of the 110 patients who underwent a graft biopsy, 47.3% exhibited ABMR, 21.8% the recurrence of glomerulonephritis, 9.1% IFTA, and 7.3% de novo glomerulonephritis. After a median follow-up of 97.5 months, 64.1% experienced graft loss. The graft survival after the onset of NP declined from 75.8% at 12 months to 38% at 5 years, without significant differences between those with and those without NS. Patients who developed NS fewer than 3 months after the onset of NP exhibited a significantly higher risk of death-censored graft loss (HR: 1.711, 95% CI: 1.147-2.553) than those without NS or those with late NS. In conclusion, NP and NS are frequent conditions after a kidney transplant, and they imply extremely poor graft outcomes. The time from the onset of NP to the development of NS is related to graft survival.

Background: Immunoglobulin A nephropathy (IgAN) is the most frequent recurrent disease in kidney transplant recipients and its recurrence contributes to reducing graft survival. Several variables at the time of recurrence have been associated with a higher risk of graft loss. The presence of clinical or subclinical inflammation has been associated with a higher risk of kidney graft loss, but it is not precisely known how it influences the outcome of patients with recurrent IgAN., Methods: We performed a multicentre retrospective study including kidney transplant recipients with biopsy-proven recurrence of IgAN in which Banff and Oxford classification scores were available. 'Tubulo-interstitial inflammation' (TII) was defined when 't' or 'i' were ≥2. The main endpoint was progression to chronic kidney disease (CKD) stage 5 or to death censored-graft loss (CKD5/DCGL)., Results: A total of 119 kidney transplant recipients with IgAN recurrence were included and 23 of them showed TII. Median follow-up was 102.9 months and 39 (32.8%) patients reached CKD5/DCGL. TII related to a higher risk of CKD5/DCGL (3 years 18.0% vs 45.3%, log-rank 7.588, P  = .006). After multivariate analysis, TII remained related to the risk of CKD5/DCGL (HR 2.344, 95% CI 1.119-4.910, P  = .024) independently of other histologic and clinical variables., Conclusions: In kidney transplant recipients with IgAN recurrence, TII contributes to increasing the risk of CKD5/DCGL independently of previously well-known variables. We suggest adding TII along with the Oxford classification to the clinical variables to identify recurrent IgAN patients at increased risk of graft loss who might benefit from intensified immunosuppression or specific IgAN therapies., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Purpose: This study presents a treatment planning system for intraoperative low-energy photon radiotherapy based on photogrammetry from real images of the surgical site taken in the operating room., Material and Methods: The study population comprised 15 patients with soft-tissue sarcoma. The system obtains the images of the area to be irradiated with a smartphone or tablet, so that the absorbed doses in the tissue can be calculated from the reconstruction without the need for computed tomography. The system was commissioned using 3D printing of the reconstructions of the tumor beds. The absorbed doses at various points were verified using radiochromic films that were suitably calibrated for the corresponding energy and beam quality., Results: The average reconstruction time of the 3D model from the video sequence in the 15 patients was 229,6±7,0 s. The entire procedure, including video capture, reconstruction, planning, and dose calculation was 520,6±39,9 s. Absorbed doses were measured on the 3D printed model with radiochromic film, the differences between these measurements and those calculated by the treatment planning system were 1.4% at the applicator surface, 2.6% at 1 cm, 3.9% at 2 cm and 6.2% at 3 cm., Conclusions: The study shows a photogrammetry-based low-energy photon IORT planning system, capable of obtaining real-time images inside the operating room, immediately after removal of the tumor and immediately before irradiation. The system was commissioned with radiochromic films measurements in 3D-printed model., 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 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

In this paper we present the results of a study of different populations of the genus Tyrrhenoleuctra, which includes morphologically cryptic species, in the Iberian Peninsula. A total of six populations were analysed from a molecular point of view and a behavioural study was conducted on three of them. Two phylogenetic trees, maximum likelihood (ML) and neighbour joining (NJ), were constructed using both new COI sequences and COI sequences already available in GenBank. Furthermore, intra- and interspecific p-distances were calculated within and between sequences of the different populations. As regards behavioural analyses, the male call of individuals from three of the studied populations was recorded, analysed and described. Both phylogenetic approaches used, ML and NJ, were congruent in discriminating five well-defined clusters, representing the four known Iberian Tyrrhenoleuctra species and a previously unknown taxon. The sequences from the six studied populations produced in this study fell within two clades: T. lusohispanica (four populations) and the new taxon (two populations). These results were supported also by the behavioral study, in which the drumming calls of individuals belonging to the two clades differed in some important parameters such as the number of sequences, intersequence interval and interbeat interval. The obtained results expand the previously known distribution of T. lusohispanica and show the existence of a new species (Tyrrhenoleuctra hynesi sp. n.) within this genus from a more restricted area, that will be described in this paper.

This work presents a multi-objective optimization strategy for fair vaccine allocation through different fairness schemes. The proposed approach considers a diverse series of parameters related to different public health data and social behaviors that influence the correct distribution of vaccines, such as corruption and crime. Simultaneously, the formulation includes prioritizing those groups with the highest risk based on the epidemiological traffic light. Furthermore, the presented strategy involves different budget constraints that allow identifying trade-off solutions through Pareto fronts. Therefore, vaccine allocations are obtained by combining fairness concepts with multi-objective optimization. The applicability of the model is illustrated using the case study of Mexico. The solution to the proposed scenarios was carried out using different justice schemes and an economic objective function. The results show the compromises between a satisfaction index and costs, which are shown through Pareto optimal solutions that allow selecting the solutions that balance the objectives. The solutions provided by the social welfare scheme suggest a greater allocation of vaccines to those states with higher epidemiological risk, which may be helpful in the first stage of vaccination. On the other hand, the Rawlsian scheme provides more balanced solutions that can be useful in situations with lower rates of infection. Finally, the Nash scheme is the one that provides the most balanced solutions, favoring to a lesser extent the areas with the highest epidemiological risk, which may be useful in the later stages of vaccination., Competing Interests: The authors declare that they have no conflict of interest., (© 2023 Elsevier Ltd. All rights reserved.)

This paper provides a mathematical optimization strategy for optimal municipal solid waste management in the context of the COVID-19 epidemic. This strategy integrates two approaches: optimization and machine learning models. First, the optimization model determines the optimal supply chain for the municipal waste management system. Then, machine learning prediction models estimate the required parameters over time, which helps generate future projections for the proposed strategy. The optimization model was coded in the General Algebraic Modeling System, while the prediction model was coded in the Python programming environment. A case study of New York City was addressed to evaluate the proposed strategy, which includes extensive socioeconomic data sets to train the machine learning model. We found the predicted waste collection over time based on the socioeconomic data. The results show trade-offs between the economic (profit) and environmental (waste sent to landfill) objectives for future scenarios, which can be helpful for possible pandemic scenarios in the following years., Supplementary Information: The online version contains supplementary material available at 10.1007/s10668-023-03354-2., Competing Interests: Conflict of interestThe authors have no conflicts of interest to declare that are relevant to the content of this article., (© The Author(s), under exclusive licence to Springer Nature B.V. 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: In metabarcoding analyses, the taxonomic assignment is crucial to place sequencing data in biological and ecological contexts. This fundamental step depends on a reference database, which should have a good taxonomic coverage to avoid unassigned sequences. However, this goal is rarely achieved in many geographic regions and for several taxonomic groups. On the other hand, more is not necessarily better, as sequences in reference databases belonging to taxonomic groups out of the studied region/environment context might lead to false assignments., Methods: We investigated the effect of using several subsets of a cytochrome c oxidase subunit I (COI) reference database on taxonomic assignment. Published metabarcoding sequences from the Mediterranean Sea were assigned to taxa using COInr, which is a comprehensive, non-redundant and recent database of COI sequences obtained both from BOLD and NCBI, and two of its subsets: (i) all sequences except insects (COInr-WO-Insecta), which represent the overwhelming majority of COInr database, but are irrelevant for marine samples, and (ii) all sequences from taxonomic families present in the Mediterranean Sea (COInr-Med). Four different algorithms for taxonomic assignment were employed in parallel to evaluate differences in their output and data consistency., Results: The reduction of the database to more specific custom subsets increased the number of unassigned sequences. Nevertheless, since most of them were incorrectly assigned by the less specific databases, this is a positive outcome. Moreover, the taxonomic resolution (the lowest taxonomic level to which a sequence is attributed) of several sequences tended to increase when using customized databases. These findings clearly indicated the need for customized databases adapted to each study. However, the very high proportion of unassigned sequences points to the need to enrich the local database with new barcodes specifically obtained from the studied region and/or taxonomic group. Including novel local barcodes to the COI database proved to be very profitable: by adding only 116 new barcodes sequenced in our laboratory, thus increasing the reference database by only 0.04%, we were able to improve the resolution for ca. 0.6-1% of the Amplicon Sequence Variants (ASVs)., Competing Interests: José Miguel Gutiérrez is employed by TAXON Estudios Ambientales S.L. as Joint Chief Executive Officer., (©2022 Mugnai et al.)

Objectives: The number of kidney transplants obtained from controlled donations after circulatory death is increasing, with long-term outcomes similar to those obtained with donations after brain death. Extraction using normothermic regional perfusion can improve results with controlled donors after circulatory death; however, information on the histological impact and extraction procedure is scarce., Materials and Methods: We retrospectively investigated all kidney transplants performed from October 2014 to December 2019, in which a follow-up kidney biopsy had been performed at 1-year follow-up, comparing controlled procedures with donors after circulatory death and normothermic regional perfusion versus donors after brain death. Interstitial fibrosis/tubular atrophy was assessed by adding the values of interstitial fibrosis and tubular atrophy, according to the Banff classification of renal allograft pathology., Results: When we compared histological data from 66 transplants with donations after brain death versus 24 transplants with donations after circulatory death and normothermic regional perfusion, no differences were found in the degree of fibrosis in the 1-year follow-up biopsy (1.7 ± 1.3 vs 1.7 ± 1.1; P = .971) or in the ratio of patients with increased fibrosis calculated as interstitial fibrosis/tubular atrophy >2 (18% vs 13%; P = .522). In our multivariate analysis, which included acute rejection, expanded criteria donation, and the type of donation, no variable was independently related to an increased risk of interstitial fibrosis/tubular atrophy >2., Conclusions: The outcomes of kidney grafts procured in our center using controlled procedures with donors after circulatory death and normothermic regional perfusion were indistinguishable from those obtained from donors after brain death, showing the same degree of fibrosis in the 1-year posttransplant surveillance biopsy. Our data support the conclusion that normothermic regional perfusion should be the method of choice for extraction in donors after circulatory death.

The aim of this work is to investigate the effectiveness of Deep Brain Stimulation (DBS) in patients with severe Obsessive Compulsive Disorder (OCD) who are resistant to pharmacological treatments, focusing on obsessive compulsive, depressive and anxiety symptoms as well as global function. A systematic review and meta-analysis including 25 studies (without language restrictions) from between 2003 and 2020 was performed. A total of 303 patients were evaluated twice (before and after DBS). After DBS treatment OCD patients with resistance to pharmacological treatments showed a significant improvement of obsessive-compulsive symptoms (25 studies; SMD=2.39; 95% CI, 1.91 to 2.87; P<0.0001), depression (9 studies; SMD= 1.19; 95%CI, 0.84 to 1.54; P<0.0001), anxiety (5 studies; SMD=1.00; 95%CI, 0.32 to 1.69; P=0.004) and functionality (7 studies; SMD=-3.51; 95%CI, -5.00 to -2.02; P=0.005) measured by the standardized scales: Yale Brown Obsessive Compulsive Scale (YBOCS), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A) and Global Assessment of Function (GAF). Publication bias were discarded by using funnel plot. The main conclusions of this meta-analysis highlight the statistically significant effectiveness of DBS in patients with severe OCD who are resistant to conventional pharmacological treatments, underlying its role in global functioning apart from obsessive-compulsive symptoms., Competing Interests: Declaration of Competing Interest The researchers report no biomedical financial interests or potential conflicts of interests., (Copyright © 2022. Published by Elsevier B.V.)

In the diatom Phaeodactylum tricornutum , iron limitation promotes a decrease in the content of photosystem II, as determined by measurements of oxygen-evolving activity, thermoluminescence, chlorophyll fluorescence analyses and protein quantification methods. Thermoluminescence experiments also indicate that iron limitation induces subtle changes in the energetics of the recombination reaction between reduced Q B and the S 2 /S 3 states of the water-splitting machinery. However, electron transfer from Q A to Q B , involving non-heme iron, seems not to be significantly inhibited. Moreover, iron deficiency promotes a severe decrease in the content of the extrinsic PsbV/cytochrome c 550 subunit of photosystem II, which appears in eukaryotic algae from the red photosynthetic lineage (including diatoms) but is absent in green algae and plants. The decline in the content of cytochrome c 550 under iron-limiting conditions is accompanied by a decrease in the binding of this protein to photosystem II, and also of the extrinsic PsbO subunit. We propose that the lack of cytochrome c 550 , induced by iron deficiency, specifically affects the binding of other extrinsic subunits of photosystem II, as previously described in cyanobacterial PsbV mutants.

Assessing the security of the water-energy-food nexus is a topic of great importance, which allows determining the situation of each resource to implement actions for sustainable management of these resources in today's society. For this reason, a systematic procedure is proposed to evaluate the synergies of the water-energy-food nexus in a large region that is divided into subregions that allow considering their interactions. The new procedure considers the availability, accessibility and regional interdependence of resources while annexing economic and social aspects. A composite index called the WEF Global Index is developed, which involves the WEF nexus index and has nine indicators that evaluate the availability, accessibility and regional interdependence of each resource in the water-energy-food nexus. This new index considers the Gross Domestic Product per capita and the involved population. As a case study, the 32 states of Mexico were considered to assess the effects of the COVID-19 pandemic on the economy and the security of the water-energy-food nexus at the state level. For this, the composite index was evaluated in the years 2019 and 2020. The results show that from 2019 to 2020, the value of the global index increased in 13 states, in 21 states the security index of the WEF nexus increased, and in 9 states the GDP per capita index increased. On the other hand, the results indicate that in 11 states there was no improvement in the nexus security index due to the increase in water demand, which considerably affected the water availability indicator., Supplementary Information: The online version contains supplementary material available at 10.1007/s10668-022-02671-2., Competing Interests: Conflict of interestThe authors have no conflicts of interest to declare that are relevant to the content of this article., (© The Author(s), under exclusive licence to Springer Nature B.V. 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Leptospirosis is a widely distributed zoonosis caused by pathogenic strains of bacteria of the genus Leptospira (Phylum Spirochaetes). Its agents are commonly classified based on their antigenic characteristics into serogroups and serovars, which are relevant for epidemiologic studies and vaccine development. Serological tests are considered laborious and require a specialized infrastructure. Some molecular methods have been proposed to accelerate these procedures, but they still can not replace the immunological tests, thus requiring a further understanding of the genetic basis underlying the serological classification. In this work, we focused on elucidating the genetic factors determinant for the serogroup Sejroe, which is one of the most prevalent serogroups in livestock. For this, we conducted a comparative analysis using >700 leptospiral genomic samples available in the public database. The analysis showed that the genes comprising the rfb locus are the main genetic factors associated with the serological classification. Samples from the serogroup Sejroe have an rfb locus with a conserved gene composition that differs from most other serogroups. Hebdomadis and Mini were the only serogroups whose samples have an rfb locus with similar gene composition to those from serogroup Sejroe, corroborating with the serological affinity shared by them. Finally, we could determine a small region in the rfb locus in which each of those three serogroups can be distinguished by its gene composition. This is the first work that uses an extensive repertoire of genomic data of leptospiral samples to elucidate the molecular basis of the serological classification and open the road to more reliable strategies based on molecular methods for serodiagnosis., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Smartphones have evolved from being a helpful tool in our days to be an indispensable complement. Its presence in our daily lives has grown to reach a problematic use on occasions. This fact is even more remarkable when we speak of young adults and adolescents, in which problematic situations can be identified as derived from its use. In this study, we analyze the self-perception of 409 young adults pursuing an Education university degree on the use and consumption of the smartphone via their responses to the Mobile Phone Problem Use Scale. The results show that, despite not perceiving the use of the mobile phone as problematic, some of the behaviors described by them as habitual would imply inappropriate use of the smartphone. Some outlined by the sample included mitigating loneliness, fear of isolation, or using it to feel better. Surprisingly, these are not recognized as problematic, despite being some of the most apparent indicators of misuse. The analysis of the results shows how younger populations and, mainly women, present this type of worrying and unconscious behavior. However, the increasing use of these devices within training areas offer new options to favor its proper use, mitigating the possible adverse effects of its use., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Introduction: Alcohol and tobacco are commonly used together. Social influences within online social networking platforms contribute to youth and young adult substance use behaviors. This study used a sample of alcohol- and tobacco-related tweets to evaluate: (1) sentiment toward co-use of alcohol and tobacco, (2) increased susceptibility to tobacco use when consuming alcohol, and (3) the role of alcohol in contributing to a failed attempt to quit tobacco use., Methods: Data were collected from the Twitter API from January 1, 2019 through December 31, 2019 using tobacco-related keywords (e.g., vape, ecig, smoking, juul*) and alcohol-related filters (e.g., drunk, blackout*). A total of 78,235 tweets were collected, from which a random subsample (n = 1,564) was drawn for coding. Cohen's Kappa values ranged from 0.66 to 0.99., Results: Most tweets were pro co-use of alcohol and tobacco (75%). One of every ten tweets reported increased susceptibility to tobacco use when intoxicated. Non-regular tobacco users reported cravings for and tobacco use when consuming alcohol despite disliking tobacco use factors such as the taste, smell, and/or negative health effects. Regular tobacco users reported using markedly higher quantities of tobacco when intoxicated. Individuals discussed the role of alcohol undermining tobacco cessation attempts less often (2.0%), though some who had quit smoking for prolonged periods of time reported reinitiating tobacco use during acute intoxication episodes., Conclusions: Tobacco cessation interventions may benefit from including alcohol-focused components designed to educate participants about the association between increased susceptibility to tobacco use when consuming alcohol and the role of alcohol in undermining tobacco cessation attempts., Implications: Sentiment toward co-use of alcohol and tobacco on Twitter is largely positive. Individuals reported regret about using tobacco, or using more than intended, when intoxicated. Those who had quit smoking or vaping for prolonged periods of time reported reinitiating tobacco use when consuming alcohol. While social media-based tobacco cessation interventions like the Truth Initiative's "Ditch the Juul" campaign demonstrate potential to change tobacco use behaviors, these campaigns may benefit from including alcohol-focused components designed to educate participants about the association between increased susceptibility to tobacco use when consuming alcohol and the role of alcohol in undermining tobacco cessation attempts., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

There have been many problems generated by the COVID-19 pandemic. One of them is the worrying increase in the generation of medical waste due to the great risk they represent for health. Therefore, this work proposes a mathematical model for optimal solid waste management, proposing a circular value chain where all types of waste are treated in an intensified industrial park. The model selects the processing technologies and their production capacity. The problem was formulated as a mixed-integer linear programming problem to maximize profits and the waste processed, minimizing environmental impact. The proposed strategy is applied to the case study of the city of New York, where the increase in the generation of medical waste has been very significant. To promote recycling, different tax rates are proposed, depending on the amount of waste sent to the landfill. The results are presented on a Pareto curve showing the trade-off between profits and processed waste. We observed that the taxes promote recycling, even of those wastes that are not very convenient to recycle (from an economic point of view), favoring profits, reducing the environmental impact, and the risk to health inherent to the medical waste., 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., (© 2022 Elsevier B.V. All rights reserved.)

Background: Arthroscopic tibiotalocalcaneal arthrodesis with a retrograde nail is performed as a minimally invasive technique in patients without improvement in conservative treatment of osteoarthritis. Complications and hospital stay after surgery are less using this technique when they are compared with open ones., Materials and Methods: We review retrospectively from 2016 to 2019 seven patients subjected to a posterior arthroscopic tibiotalocalcaneal arthrodesis with a retrograde intramedullary nail. AOFAS scale was used to assess functional results and we collected other data as complications, time required for bony union, time of nonweight-bearing and scale of satisfaction. We also made a description of the technique we performed., Results: The mean hospital stay was 3.43±0.53 days, patients have well functional results and complications were very low. It was noticed tibiotalar bony union in about 86% of patients 10 weeks after surgery and subtalar bony union in about 71% 20 weeks after surgery. Nonweight-bearing was made using a cast for 4 weeks and later, it was changed for Walker allowing patients partial weight-bearing until 10 weeks after surgery. One patient had wound complications and he needed later surgery and another presented tibiotalar pseudoarthrosis, although without symptoms., Conclusion: Posterior arthroscopic tibiotalocalcaneal arthrodesis offers very good results with a high rate of bony union, few complications, and minimal nonweight-bearing time. This technique could be used in patients without major deformities, especially in those at high risk of complications from the surgical wound., (Publicado por Elsevier España, S.L.U.)

Background: Urinary CXCL10 (uCXCL10) is associated with graft inflammation and graft survival, but the factors related to its excretion are not well known. HLA molecular matching at epitope level allow estimating the "dissimilarity" between donor and recipient HLA more precisely, being better related to further transplant outcomes. The relationship between uCXCL10 and HLA molecular mismatch has not been previously explored., Methods: HLA class I and class II typing of some 65 recipients and their donors was retrospectively performed by high resolution sequence-specific-primer (Life Technologies, Brown Deer, WI). The HLA-Matchmaker 3.1 software was used to assess eplet matching. Urine samples collected on the day of the 1-year surveillance biopsy were available of these 65 patients. uCXCL10 was measured using a commercial enzyme-linked immunoassay kit., Results: 1-year uCXCL10 was independently associated with HLA-DQB1 eplet mismatch load (β 0.300, 95%CI 0.010-0.058, p = 0.006). Kidney transplant recipients with a HLA-DQB1 eplet mismatch load >3 showed higher values of uCXCL10 at 1-year (p = 0.018) than those with ≤3. Patients with a HLA-DQB1 eplet mismatch load >3 with subclinical AbMR had significantly higher levels of the logarithm of 1-year uCXCL10 (No AbMR 0.88, IQR 0.37; AbMR 1.38, IQR 0.34, p = 0.002) than those without AbMR., Conclusions: uCXCL10 specifically relates to HLA-DQ eplet mismatch load. This relationship can partly explain the previously reported association between uCXCL10 excretion and graft inflammation. An adequate evaluation of any potential non-invasive biomarker, such as uCXCL10, must take into account the HLA molecular mismatch., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

In the diagnostic of systemic sclerosis (SSc), both anti-centromere (ACA) and anti-topoisomerase I (ATA) antibodies are considered mutually exclusive, though their coexistence has been also reported in some patients. Notably, nintedanib has been approved for the treatment of interstitial lung disease associated to SSc. Herein, we present the clinical case of a 41-year-old woman with SSc who shows an immunological seroconversion (from ACA positivity to a coexistence of ACA and ATA antibodies) together with changes in her clinical phenotype. Besides, the patient responds positively to the treatment of her lung involvement with a combination of immunomodulators and antifibrotic agents.

This paper presents a comparison of six index properties collected during durability inspections of five Mexican seaports. Typical durability indicators such as compressive strength, saturated electrical resistivity, ultrasonic pulse velocity, percent total void content, capillary porosity, and chloride concentration profiles were analyzed to obtain empirical correlations with the non-steady-state chloride diffusion coefficient. These indices were compared to determine correlation coefficients that are the most important for obtaining better corrosion initiation forecasting. Two models of corrosion initiation time (t i ) were used: Fick's second law of diffusion and the reported UNE-83994-2 (Spanish Association for Standardization, UNE) in which electrical resistivity was used to calculate concrete service life. The data from both models were cleaned using correlated variables, and the initial variables were compared with t i . The main result achieved was the verification of the feasibility of using correlations of variables to clean unnecessary data in order to calculate t i . Additionally, electrical resistivity was identified as one of the main durability indexes for in-service concrete structures exposed to marine environments. This is important because electrical resistivity is a non-destructive and reliable test that can be measured both in the laboratory and in the field very easily.

The use of eco-friendly cements prepared with ternary binders could contribute to improving the sustainability of cement production. However, their use for manufacturing commercial cements is very low, at least in Spain. The purpose of this research is to study the behavior in the long term of mortars made with ternary binders which incorporated ground granulated blast furnace slag, fly ash, and limestone, exposed to environmental conditions compatible with the specifications of exposure class XC3 of the Eurocode 2, compared to mortars without additions and mortars with binary binders. The exposure station was placed in an underground floor of a building used as a garage with circulation of vehicles and moderately high CO 2 concentration. The ternary and binary binders verified the prescriptions of cement type CEM II/B. The microstructure was characterized using mercury intrusion porosimetry and electrical resistivity. Water absorption, diffusion coefficient, carbonation depth, mechanical strengths, and ultrasonic pulse velocity were determined. A loss of microstructure refinement with time was noted for all the analyzed binders, probably related to the development of carbonation and drying shrinkage. The binary mortars with slag and fly ash and the ternary binder which combined them showed the best mechanical performance at 250 days.

For improving the contribution of the cement industry to mitigate global warming, many strategies have been put into practice, such as the use of eco-friendly cements with the incorporation of additions substituting clinker. Nevertheless, the use of ternary binders for the production of commercial cements is still reduced, particularly in Spain. The purpose of this research is to characterize the long-term influence produced by the exposure to a real in situ inland Mediterranean climate condition in the pore network, parameters related to durability and mechanical performance of mortars made with ternary binders, which incorporated limestone, fly ash, and ground granulated blast-furnace slag, in comparison with mortars without additions and binary blended mortars. The site verified the specifications of exposure class XC4 of Eurocode 2. The ternary and binary binders accomplished the prescriptions of cement type CEM II/B. The pore network was studied with mercury intrusion porosimetry and electrical resistivity. Water absorption, diffusion coefficient, carbonation depth, ultrasonic pulse velocity, compressive and flexural strengths have been determined. The exposure to the environment produced after 250 days an increase in porosity, a loss of pore refinement, a rise of the carbonation depths, and a reduction in the mechanical strengths, highlighting the better overall performance of ternary mortar with both fly ash and slag.

Bioinformatics is a fast-evolving research field, requiring effective educational initiatives to bring computational knowledge to Life Sciences. Since 2017, an organizing committee composed of graduate students and postdoctoral researchers from the Universidade Federal de Minas Gerais (Brazil) promotes a week-long event named Summer Course in Bioinformatics (CVBioinfo). This event aims to diffuse bioinformatic principles, news, and methods mainly focused on audiences of undergraduate students. Furthermore, as the advent of the COVID-19 global pandemic has precluded in-person events, we offered the event in online mode, using free video transmission platforms. Herein, we present and discuss the insights obtained from promoting the Online Workshop in Bioinformatics (WOB) organized in November 2020, comparing it to our experience in previous in-person editions of the same event., 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 da Silva, Abreu, Mariano, Caixeta, Santos, Lage, Quintanilha-Peixoto, Hilário, Xavier, Queiroz, de Toledo, Tavares, Kato, dos Santos, Soares, Goes, Nogueira, Batista, Ortega, De Carvalho, Franco, Melo-Minardi and Góes-Neto.)

Objective: The purpose of this study was to characterize the content and themes present in user-generated TikTok videos portraying alcohol., Method: We captured the 100 most popular videos including the #alcohol hashtag on the popular social networking site TikTok. We used an iterative process to codebook development, resulting in codes for user sentiment toward alcohol, type of alcohol depicted, brand references, degree of alcohol use, and positive/negative associations with alcohol use. Videos were independently double coded, evaluated for inter-rater agreement, and adjudicated if differences were present., Results: The videos in our sample were collectively viewed 291,999,100 times. The vast majority (98%) of videos expressed pro-alcohol sentiment. Nearly half of videos (41%) were guide videos demonstrating drink recipes. The majority of videos (72%) included liquor. Consuming multiple drinks quickly was depicted in more than half of videos (61%), whereas intoxication (13%) was exhibited less frequently. Positive associations with alcohol were prevalent; 69% of videos conveyed positive experiences with alcohol, 55% of videos contained humor, and 45% included associations of alcohol with camaraderie. Negative associations with alcohol were rarely portrayed (4%)., Conclusions: Top alcohol-related videos on TikTok are heavily viewed. Their contents demonstrate a propensity to promote rapid consumption of multiple drinks and to juxtapose alcohol use with positive associations such as humor and camaraderie, while rarely depicting negative outcomes associated with hazardous alcohol use.

Background: Sequential treatment of Panitumumab (Pb) plus Paclitaxel (Px) as induction treatment (IT) followed by concurrent bioradiotherapy (Bio-RT) with Pb may be an alternative for locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) in patients ineligible for high-dose cisplatin therapy., Methods: Phase II, single-arm, multicentre study, with two-stage design, in patients ≥ 18 years with stage III-IVa-b LA-SCCHN unfit for platinum. Patients received Px + Pb (9 weeks) as IT followed by Bio-RT + Pb. Primary endpoint: overall response rate (ORR) after IT, defined as: more than 70% of patients achieving complete response (CR) or partial response (PR) to IT. Secondary end-points: progression-free survival, organ preservation rate, safety profile., Results: Study ended prematurely (51 patients) due to slow recruitment. ORR: 66.7% (95% CI: 53.7-79.6), 8 (15.7%) CR and 26 (51.0%) PR. 39 patients (76%) completed radiotherapy (RT). Pb and/or Px-related adverse events (AEs) grade 3-4: 56.9% during IT and 63.4% during the concomitant phase, of which most common were skin toxicity (33.3%). Five deaths occurred during treatment, two of them (3.9%) were Pb and/or Px-related., Conclusions: Although underpowered, ORR was higher than the pre-specified boundary for considering the treatment active. Although Px + Pb as IT provides some benefit, the safety profile is worse than expected. To consider Pb + Px as IT as an alternative for platinum-unsuitable LA-SCCHN, further research/investigation would be needed.