Mimotope discovery as a tool to design a vaccine against Zika and dengue viruses.

Vaccine development against dengue virus is challenging because of the antibody-dependent enhancement of infection (ADE), which causes severe disease. Consecutive infections by Zika (ZIKV) and/or dengue viruses (DENV), or vaccination can predispose to ADE. Current vaccines and vaccine candidates contain the complete envelope viral protein, with epitopes that can raise antibodies causing ADE. We used the envelope dimer epitope (EDE), which induces neutralizing antibodies that do not elicit ADE, to design a vaccine against both flaviviruses. However, EDE is a discontinuous quaternary epitope that cannot be isolated from the E protein without other epitopes. Utilizing phage display, we selected three peptides that mimic the EDE. Free mimotopes were disordered and did not elicit an immune response. After their display on adeno-associated virus (AAV) capsids (VLP), they recovered their structure and were recognized by an EDE-specific antibody. Characterization by cryo-EM and enzyme-linked immunosorbent assay confirmed the correct display of a mimotope on the surface of the AAV VLP and its recognition by the specific antibody. Immunization with the AAV VLP displaying one of the mimotopes induced antibodies that recognized ZIKV and DENV. This work provides the basis for developing a Zika and dengue virus vaccine candidate that will not induce ADE.

IL-6 serum levels predict severity and response to tocilizumab in COVID-19: An observational study.

BACKGROUND: Patients with coronavirus disaese 2019 (COVID-19) can develop a cytokine release syndrome that eventually leads to acute respiratory distress syndrome requiring invasive mechanical ventilation (IMV). Because IL-6 is a relevant cytokine in acute respiratory distress syndrome, the blockade of its receptor with tocilizumab (TCZ) could reduce mortality and/or morbidity in severe COVID-19. OBJECTIVE: We sought to determine whether baseline IL-6 serum levels can predict the need for IMV and the response to TCZ. METHODS: A retrospective observational study was performed in hospitalized patients diagnosed with COVID-19. Clinical information and laboratory findings, including IL-6 levels, were collected approximately 3 and 9 days after admission to be matched with preadministration and postadministration of TCZ. Multivariable logistic and linear regressions and survival analysis were performed depending on outcomes: need for IMV, evolution of arterial oxygen tension/fraction of inspired oxygen ratio, or mortality. RESULTS: One hundred forty-six patients were studied, predominantly males (66%); median age was 63 years. Forty-four patients (30%) required IMV, and 58 patients (40%) received treatment with TCZ. IL-6 levels greater than 30 pg/mL was the best predictor for IMV (odds ratio, 7.1; P < .001). Early administration of TCZ was associated with improvement in oxygenation (arterial oxygen tension/fraction of inspired oxygen ratio) in patients with high IL-6 (P = .048). Patients with high IL-6 not treated with TCZ showed high mortality (hazard ratio, 4.6; P = .003), as well as those with low IL-6 treated with TCZ (hazard ratio, 3.6; P = .016). No relevant serious adverse events were observed in TCZ-treated patients. CONCLUSIONS: Baseline IL-6 greater than 30 pg/mL predicts IMV requirement in patients with COVID-19 and contributes to establish an adequate indication for TCZ administration.

Heterogeneity in Quality of Life of Long-Term Colon Cancer Survivors: A Latent Class Analysis of the Population-Based PROFILES Registry.

BACKGROUND: Long-term colon cancer survivors present heterogeneous health-related quality of life (HRQOL) outcomes. We determined unobserved subgroups (classes) of survivors with similar HRQOL patterns and investigated their stability over time and the association of clinical covariates with these classes. MATERIALS AND METHODS: Data from the population-based PROFILES registry were used. Included were survivors with nonmetastatic (TNM stage I-III) colon cancer (n = 1,489). HRQOL was assessed with the Dutch translation of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 version 3.0. Based on survivors' HRQOL, latent class analysis (LCA) was used to identify unobserved classes of survivors. Moreover, latent transition analysis (LTA) was used to investigate changes in class membership over time. Furthermore, the effect of covariates on class membership was assessed using multinomial logistic regression. RESULTS: LCA identified five classes at baseline: class 1, excellent HRQOL (n = 555, 37.3%); class 2, good HRQOL with prevalence of insomnia (n = 464, 31.2%); class 3, moderate HRQOL with prevalence of fatigue (n = 213, 14.3%); class 4, good HRQOL with physical limitations (n = 134, 9.0%); and class 5, poor HRQOL (n = 123, 8.3%). All classes were stable with high self-transition probabilities. Longer time since the diagnosis, no comorbid conditions, and male sex were associated with class 1, whereas older age was associated with class 4. Clinical covariates were not associated with class membership. CONCLUSION: The identified classes are characterized by distinct patterns of HRQOL and can support patient-centered care. LCA and LTA are powerful tools for investigating HRQOL in cancer survivors. IMPLICATIONS FOR PRACTICE: Long-term colon cancer survivors show great heterogeneity in their health-related quality of life. This study identified five distinct clusters of survivors with similar patterns of health-related quality of life and showed that these clusters remain stable over time. It was also shown that these clusters do not significantly differ in tumor characteristics or received treatment. Cluster membership of long-term survivors can be identified by sociodemographic characteristics but is not predetermined by diagnosis and treatment.

Evaluation of diagnostic accuracy of 10 serological assays for detection of SARS-CoV-2 antibodies.

Antibody detection is essential to establish exposure, infection, and immunity to SARS-CoV-2, as well as to perform epidemiological studies. The worldwide urge for new diagnostic tools to control the pandemic has led to a quick incorporation in clinical practice of the recently developed serological assays. However, as only few comparative studies have been published, there is a lack of data about the diagnostic accuracy of currently available assays. We evaluated the diagnostic accuracy to detect Ig G, Ig M+A, and/or IgA anti SARS-CoV-2 of 10 different assays: lateral flow card immunoassays, 4 enzyme-linked immunosorbent assay (ELISA), and 3 chemiluminescent particle immunoassays (CMIA). Using reverse transcriptase polymerase chain reaction (RT-PCR) for COVID-19 as gold standard, sensitivity, specificity, PPV, and NPV were determined. Each assay was tested in 2 groups, namely, positive control, formed by 50 sera from 50 patients with SARS-CoV-2 pneumonia with positive RT-PCR; and negative control, formed by 50 sera from 50 patients with respiratory infection non-COVID-19. Sensitivity range of the 10 assays evaluated for patients with positive COVID-19 RT-PCR was 40-77% (65-81% considering IgG plus IgM). Specificity ranged 83-100%. VPP and VPN were respectively 81-100% and 61.6-81%. Among the lateral flow immunoassays, the highest sensitivity and specificity results were found in Wondfo® SARS-CoV-2 Antibody Test. ELISA IgG and IgA from EUROIMMUN® were the most sensitive ELISA. However, poor results were obtained for isolated detection of IgG. We found similar sensitivity for IgG with SARS-CoV-2 for Architect by Abbott® and ELISA by Vircell®. Results obtained varied widely among the assays evaluated. Due to a better specificity, overall diagnostic accuracy of the assays evaluated was higher in case of positive result. On the other side, lack of antibody detection should be taken with care because of the low sensitivity described. Highest diagnostic accuracy was obtained with ELISA and CMIAs, but they last much longer.

A case report of transmission and disease caused by Mycobacterium caprae and Mycobacterium bovis in Lima, Peru.

BACKGROUND: The Tuberculosis (TB) burden in Peru is significant with respect to both disease morbidity and mortality. Furthermore the recent diversification of farming enterprise to include a wide range of animal species has necessitated the consideration of members of the Mycobacterium Tuberculosis Complex (MTBC) with the potential for zoonotic transmission. M. bovis and M. caprae, a lesser known member of the MTBC exhibit an exceptionally wide host spectrum in animals and are capable of causing disease in humans. M. bovis has a predictable resistance profile which includes resistance to pyrazinamide. Thus, failure to identify M. bovis as the causative agent in reported TB cases leads to higher levels of treatment failure and contributes to the transmission of drug-resistant TB. CASE PRESENTATION: Reported here are the clinical presentations, investigations and treatment histories of two patients identified from a population level genotyping study in Lima, Peru that were at the time of treatment thought to be M. tuberculosis patients but in retrospect were spectated using whole genome sequencing as M. caprae and M. Bovis. CONCLUSIONS: The cases reported here constitute convincing evidence that M. caprae and M. bovis are causative agents of TB infection in humans in Peru and underscore the importance of species-level MTBC member identification to effectively control and treat zoonotic TB. Furthermore these cases highlight the challenges of using clinical risk factors to identify cases of zoonotic TB in humans as their clinical presentation and transmission history is often difficult to distinguish from anthroponotic TB.

A comprehensive and comparative phenotypic analysis of the collaborative founder strains identifies new and known phenotypes.

The collaborative cross (CC) is a large panel of mouse-inbred lines derived from eight founder strains (NOD/ShiLtJ, NZO/HILtJ, A/J, C57BL/6J, 129S1/SvImJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ). Here, we performed a comprehensive and comparative phenotyping screening to identify phenotypic differences and similarities between the eight founder strains. In total, more than 300 parameters including allergy, behavior, cardiovascular, clinical blood chemistry, dysmorphology, bone and cartilage, energy metabolism, eye and vision, immunology, lung function, neurology, nociception, and pathology were analyzed; in most traits from sixteen females and sixteen males. We identified over 270 parameters that were significantly different between strains. This study highlights the value of the founder and CC strains for phenotype-genotype associations of many genetic traits that are highly relevant to human diseases. All data described here are publicly available from the mouse phenome database for analyses and downloads.

Host species influence on flea (Siphonaptera) infection parameters of terrestrial micromammals in a temperate forest of Mexico.

Studies of abundance and distribution of organisms are fundamental to ecology. The identity of host species is known to be one of the major factors influencing ectoparasitic flea abundance, but explanations are still needed regarding how host taxa influence abundance parameters of different flea species. This study was carried out at La Malinche National Park (LMNP), Tlaxcala, Mexico, where previously 11 flea species had been recorded on 8 host species. Our aims were to list micromammal flea species, to determine flea infection parameters [flea prevalence (FP) and flea mean abundance (FMA)] and to analyse the influence of host species on these parameters. A total of 16 species of fleas were identified from 1178 fleas collected from 14 species of 1274 micromammals captured with Sherman® traps from March 2014 to December 2015 in 18 sites at LMNP. Some host species influence FP and FMA, in particular, Microtus mexicanus and Peromyscus melanotis showed particularly higher infection values than other host species. Plusaetis aztecus and Plusaetis sibynus were identified as the most abundant flea species.

Speech Envelope Enhancement Instantaneously Effaces Atypical Speech Perception in Dyslexia.

OBJECTIVES: Increasing evidence exists that poor speech perception abilities precede the phonological deficits typically observed in dyslexia, a developmental disorder in learning to read. Impaired processing of dynamic features of speech, such as slow amplitude fluctuations and transient acoustic cues, disrupts effortless tracking of the speech envelope and constrains the development of adequate phonological skills. In this study, a speech envelope enhancement (EE) strategy was implemented to reduce speech perception deficits by students with dyslexia. The EE emphasizes onset cues and reinforces the temporal structure of the speech envelope specifically. DESIGN: Speech perception was assessed in 42 students with and without dyslexia using a sentence repetition task in a speech-weighted background noise. Both natural and vocoded speech were used to assess the contribution of the temporal envelope on the speech perception deficit. Their envelope-enhanced counterparts were added to each baseline condition to administer the effect of the EE algorithm. In addition to speech-in-noise perception, general cognitive abilities were assessed. RESULTS: Results demonstrated that students with dyslexia not only benefit from EE but benefit more from it than typical readers. Hence, EE completely normalized speech reception thresholds for students with dyslexia under adverse listening conditions. In addition, a correlation between speech perception deficits and phonological processing was found for students with dyslexia, further supporting the relation between speech perception abilities and reading skills. Similar results and relations were found for conditions with natural and vocoded speech, providing evidence that speech perception deficits in dyslexia stem from difficulties in processing the temporal envelope. CONCLUSIONS: Using speech EE, speech perception skills in students with dyslexia were improved passively and instantaneously, without requiring any explicit learning. In addition, the observed positive relationship between speech processing and advanced phonological skills opens new avenues for specific intervention strategies that directly target the potential core deficit in dyslexia.

A framework for computational modelling of interaural time difference discrimination of normal and hearing-impaired listeners.

Different computational models have been developed to study the interaural time difference (ITD) perception. However, only few have used a physiologically inspired architecture to study ITD discrimination. Furthermore, they do not include aspects of hearing impairment. In this work, a framework was developed to predict ITD thresholds in listeners with normal and impaired hearing. It combines the physiologically inspired model of the auditory periphery proposed by Zilany, Bruce, Nelson, and Carney [(2009). J. Acoust. Soc. Am. 126(5), 2390-2412] as a front end with a coincidence detection stage and a neurometric decision device as a back end. It was validated by comparing its predictions against behavioral data for narrowband stimuli from literature. The framework is able to model ITD discrimination of normal-hearing and hearing-impaired listeners at a group level. Additionally, it was used to explore the effect of different proportions of outer- and inner-hair cell impairment on ITD discrimination.

Predicting phoneme and word recognition in noise using a computational model of the auditory periphery.

Several filterbank-based metrics have been proposed to predict speech intelligibility (SI). However, these metrics incorporate little knowledge of the auditory periphery. Neurogram-based metrics provide an alternative, incorporating knowledge of the physiology of hearing by using a mathematical model of the auditory nerve response. In this work, SI was assessed utilizing different filterbank-based metrics (the speech intelligibility index and the speech-based envelope power spectrum model) and neurogram-based metrics, using the biologically inspired model of the auditory nerve proposed by Zilany, Bruce, Nelson, and Carney [(2009), J. Acoust. Soc. Am. 126(5), 2390-2412] as a front-end and the neurogram similarity metric and spectro temporal modulation index as a back-end. Then, the correlations with behavioural scores were computed. Results showed that neurogram-based metrics representing the speech envelope showed higher correlations with the behavioural scores at a word level. At a per-phoneme level, it was found that phoneme transitions contribute to higher correlations between objective measures that use speech envelope information at the auditory periphery level and behavioural data. The presented framework could function as a useful tool for the validation and tuning of speech materials, as well as a benchmark for the development of speech processing algorithms.

In and out of refugia: historical patterns of diversity and demography in the North American Caesar's mushroom species complex.

Some of the effects of past climate dynamics on plant and animal diversity make-up have been relatively well studied, but to less extent in fungi. Pleistocene refugia are thought to harbour high biological diversity (i.e. phylogenetic lineages and genetic diversity), mainly as a product of increased reproductive isolation and allele conservation. In addition, high extinction rates and genetic erosion are expected in previously glaciated regions. Some of the consequences of past climate dynamics might involve changes in range and population size that can result in divergence and incipient or cryptic speciation. Many of these dynamic processes and patterns can be inferred through phylogenetic and coalescent methods. In this study, we first delimit species within a group of closely related edible ectomycorrhizal Amanita from North America (the American Caesar's mushrooms species complex) using multilocus coalescent-based approaches; and then address questions related to effects of Pleistocene climate change on the diversity and genetics of the group. Our study includes extensive geographical sampling throughout the distribution range, and DNA sequences from three nuclear protein-coding genes. Results reveal cryptic diversity and high speciation rates in refugia. Population sizes and expansions seem to be larger at midrange latitudes (Mexican highlands and SE USA). Range shifts are proportional to population size expansions, which were overall more common during the Pleistocene. This study documents responses to past climate change in fungi and also highlights the applicability of the multispecies coalescent in comparative phylogeographical analyses and diversity assessments that include ancestral species.

Didymium xerophilum, a new myxomycete from the tropical Andes.

A new species of Didymium (Myxomycetes), D. xerophilum, is described, and some details of its life cycle are provided. The new species was collected during studies of arid areas of Argentina and Peru. It can be distinguished by the persistent funnel-shaped invagination of the peridium, the top of which appears as a deep umbilicus in closed sporothecae, and the calcareous hypothallus shared among several sporocarps. This combination of characters, with a circumscissile dehiscence of the sporotheca and a cream stalk packed with rhombic lime crystals, is unknown in other described species. Morphology was examined with scanning electron microscopy and light microscopy, and micrographs of relevant details are included here. Phylogenetic analysis with 18S rDNA sequences of different species of Didymium supports the distinct identity of this new species. Some collections of this myxomycete were made at up to 4600 m, an altitude almost unknown for this group of microorganisms.

Detection of organochlorine pesticides in infertile eggs of crocodylus acutus from sinaloa.

Environmental contaminants endanger human health and non-target organisms such as crocodiles (Crocodylus acutus) that live in aquatic bodies surrounding agricultural areas. Due to their intrinsic characteristics, these organisms could be bioaccumulating and transmitting organochlorine pesticides (OCs) to their eggs. The objectives of this study were to determine the OCs in infertile eggs of C. acutus from Sinaloa and their correlation with the morphometric characteristics (MC), and to perform a preliminary estimate of the ecological risk due to the presence of pesticides using the PERPEST model. In June 2022, 76 infertile eggs (Ie) were collected: 57 from wild areas (Wa) and 19 from a crocodile farm (CSMf). Determination of OC in Ie was performed according to the USEPA method 8081b, modified. The observed percentages of Ie in Wa were 31.48% and 21.33% in CSMf. Twenty OCs were detected in the Ie, where dieldrin recorded the highest average concentration in Wa (6542.6 ng/g), and endosulfan-II in the CSMf (2172.8 ng/g). Bad negative and positive correlations were observed between OCs and MC, standing out the correlations between endosulfan-II and %Ie (-0.688) in the Wa, Cedritos drain, and between endrin and the weight of Ie (0.786) of the CSMf. The evaluation of the ecological risks of the aquatic environment due to the presence of OCs follow the sequence cyclodienes > aromatic > alicyclic hydrocarbons. A potential risk to the endocrine health of the species C. acutus was observed. Crocodiles are excellent biological models for monitoring the effects of OCs.

Measuring Motivation Using the Progressive Ratio Task in Adolescent Mice.

Alterations in reward seeking are a hallmark of multiple psychiatric disorders, including substance abuse and depression. One important aspect of reward seeking is 'wanting', which can be operationalized in both humans and rodents in tasks such as the progressive ratio, in which an increasing amount of work is required to earn a given reward. Importantly, many disorders with reward-seeking deficits are believed to have an important neurodevelopmental component, underscoring the importance of being able to study changes in motivation across the lifespan. Although this task has been adapted for both adult and adolescent rats, in mice it has predominantly been used to assay motivational changes in adults. Specific concerns in adapting this task from adult to adolescent mice include (1) optimizing a food restriction paradigm suitable for growing animals whose weights are naturally dynamically changing and (2) identifying task conditions that allow younger, smaller mice to perform the task while minimizing the length of the behavioral shaping required to measure motivation at specific developmental dates. Toward that end, we now report a protocol for appropriate weight management in developing animals that require food restriction, and a protocol for behavioral shaping and progressive ratio testing in adolescent mice, including an assessment of whether the animals perform better with lever presses or nose pokes as the required operant response. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Food restriction and weight management in the context of developing mice Alternate Protocol: Food restriction and weight management of developing mice without projected growth chart: Utilization of baseline mice Basic Protocol 2: Operant box design, progressive ratio training, testing, and data analysis in adolescent mice.

DNA metabarcoding reveals seasonal changes in diet composition across four arthropod-eating lizard species (Phrynosomatidae: Sceloporus).

Diet composition and its ecological drivers are rarely investigated in coexisting closely related species. We used a molecular approach to characterize the seasonal variation in diet composition in four spiny lizard species inhabiting a mountainous ecosystem. DNA metabarcoding revealed that the lizards Sceloporus aeneus, S. bicanthalis, S. grammicus, and S. spinosus mostly consumed arthropods of the orders Hemiptera, Araneae, Hymenoptera, and Coleoptera. The terrestrial lizards S. aeneus and S. bicanthalis mostly predated ants and spiders, whereas the arboreal-saxicolous S. grammicus and saxicolous S. spinosus largely consumed grasshoppers and leafhoppers. The taxonomic and phylogenetic diversity of the prey was higher during the dry season than the rainy season, likely because reduced prey availability in the dry season forced lizards to diversify their diets to meet their nutritional demands. Dietary and phylogenetic composition varied seasonally depending on the species, but only dietary composition varied with altitude. Seasonal dietary turnover was greater in S. spinosus than in S. bicanthalis, suggesting site-specific seasonal variability in prey availability; no other differences among species were observed. S. bicanthalis, which lives at the highest altitude in our study site, displayed interseasonal variation in diet breadth. Dietary differences were correlated with the species' feeding strategies and elevational distribution, which likely contributed to the coexistence of these lizard species in the studied geographic area and beyond.

A novel method for continuous measurements of clinical practice guideline adherence.

Introduction: Clinical practice guidelines (hereafter 'guidelines') are crucial in providing evidence-based recommendations for physicians and multidisciplinary teams to make informed decisions regarding diagnostics and treatment in various diseases, including cancer. While guideline implementation has been shown to reduce (unwanted) variability and improve outcome of care, monitoring of adherence to guidelines remains challenging. Real-world data collected from cancer registries can provide a continuous source for monitoring adherence levels. In this work, we describe a novel structured approach to guideline evaluation using real-world data that enables continuous monitoring. This method was applied to endometrial cancer patients in the Netherlands and implemented through a prototype web-based dashboard that enables interactive usage and supports various analyses. Method: The guideline under study was parsed into clinical decision trees (CDTs) and an information standard was drawn up. A dataset from the Netherlands Cancer Registry (NCR) was used and data items from both instruments were mapped. By comparing guideline recommendations with real-world data an adherence classification was determined. The developed prototype can be used to identify and prioritize potential topics for guideline updates. Results: CDTs revealed 68 data items for recording in an information standard. Thirty-two data items from the NCR were mapped onto information standard data items. Four CDTs could sufficiently be populated with NCR data. Conclusion: The developed methodology can evaluate a guideline to identify potential improvements in recommendations and the success of the implementation strategy. In addition, it is able to identify patient and disease characteristics that influence decision-making in clinical practice. The method supports a cyclical process of developing, implementing and evaluating guidelines and can be scaled to other diseases and settings. It contributes to a learning healthcare cycle that integrates real-world data with external knowledge.

Maternal transmission of bacterial microbiota during embryonic development in a viviparous lizard.

IMPORTANCE: We investigated the presence and diversity of bacteria in the embryos of the viviparous lizard Sceloporus grammicus and their amniotic environment. We compared this diversity to that found in the maternal intestine, mouth, and cloaca. We detected bacterial DNA in the embryos, albeit with a lower bacterial species diversity than found in maternal tissues. Most of the bacterial species detected in the embryos were also found in the mother, although not all of them. Interestingly, we detected a high similarity in the composition of bacterial species among embryos from different mothers. These findings suggest that there may be a mechanism controlling the transmission of bacteria from the mother to the embryo. Our results highlight the possibility that the interaction between maternal bacteria and the embryo may affect the development of the lizards.

A federated approach to identify women with early-stage cervical cancer at low risk of lymph node metastases.

OBJECTIVE: Lymph node metastases (pN+) in presumed early-stage cervical cancer negatively impact prognosis. Using federated learning, we aimed to develop a tool to identify a group of women at low risk of pN+, to guide the shared decision-making process concerning the extent of lymph node dissection. METHODS: Women with cervical cancer between 2005 and 2020 were identified retrospectively from population-based registries: the Danish Gynaecological Cancer Database, Swedish Quality Registry for Gynaecologic Cancer and Netherlands Cancer Registry. Inclusion criteria were: squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma; The International Federation of Gynecology and Obstetrics 2009 IA2, IB1 and IIA1; treatment with radical hysterectomy and pelvic lymph node assessment. We applied privacy-preserving federated logistic regression to identify risk factors of pN+. Significant factors were used to stratify the risk of pN+. RESULTS: We included 3606 women (pN+ 11%). The most important risk factors of pN+ were lymphovascular space invasion (LVSI) (odds ratio [OR] 5.16, 95% confidence interval [CI], 4.59-5.79), tumour size 21-40 mm (OR 2.14, 95% CI, 1.89-2.43) and depth of invasion>10 mm (OR 1.81, 95% CI, 1.59-2.08). A group of 1469 women (41%)-with tumours without LVSI, tumour size ≤20 mm, and depth of invasion ≤10 mm-had a very low risk of pN+ (2.4%, 95% CI, 1.7-3.3%). CONCLUSION: Early-stage cervical cancer without LVSI, a tumour size ≤20 mm and depth of invasion ≤10 mm, confers a low risk of pN+. Based on an international privacy-preserving analysis, we developed a useful tool to guide the shared decision-making process regarding lymph node dissection.

An Improved Infrastructure for Privacy-Preserving Analysis of Patient Data.

Incorporating healthcare data from different sources is crucial for a better understanding of patient (sub)populations. However, data centralization raises concerns about data privacy and governance. In this work, we present an improved infrastructure that allows privacy-preserving analysis of patient data: vantage6 v3. For this new version, we describe its architecture and upgraded functionality, which allows algorithms running at each party to communicate with one another through a virtual private network (while still being isolated from the public internet to reduce the risk of data leakage). This allows the execution of different types of algorithms (e.g., multi-party computation) that were practically infeasible before, as showcased by the included examples. The (continuous) development of this type of infrastructure is fundamental to meet the current and future demands of healthcare research with a strong emphasis on preserving the privacy of sensitive patient data.

Historical analysis of an imperiled fish species: environmental variables modeling, biotic interactions, extirpation, and current restricted-range.

BACKGROUND: Analyses of spatial and temporal patterns and interactions are important for determining the abiotic factors limiting populations and the impact from other species and different anthropogenic stressors that promote the extirpation of species. The fish Hubbsina turneri de Buen (1940) was studied as a model species in a historical context at varying locations. Originally distributed only in the Lerma-Chapala basin, the main lake complex in Mexico, this species has not been collected from Lake Cuitzeo (LC) and now is restricted to Lake Zacapu (LZ). At present, the Highland splitfin is classified as critically endangered. METHODS: Historical information of LC and historical and current information from LZ were explored by applying cluster analysis and generalized additive mixed model (GAMM) to describe the biotic interactions among fish species and the relationship between density and environmental variables, respectively. The two lakes' contrasting abiotic/biotic characteristics provided elements to describe some species distribution limits in chemical ion gradients. Extirpation calendar dates were estimated using an optimal linear estimation method. Finally, a bibliographic review was conducted on the causes that promoted the extirpation and restriction of H. turneri and the prognosis for its reestablishment and conservation. RESULTS: Clusters showed the fishes relationship according to their distribution along the lakes. GAMM indicated that high H. turneri density is related to low hardness/fecal coliforms, medium depth/suspended solids, and high oxygen concentration. Estimated extirpation dates were between the years 2013 and 2018. The extirpation was linked to an abrupt drop in the LC volume, water quality degradation, increased biotic interactions within macrophytes habitats with native and introduced species, and fisheries bycatches. The current restricted range of H. turneri resulted from the draining of the larger lake, forcing the remaining populations to small spring-fed remnants. Recent samplings in LZ resulted in a low number of individuals. CONCLUSIONS: The integration of ecological interactions derived from statistical models, extirpation dates from nonparametric tests, and the exhaustive analysis of historical information can be applied to define the current situation of imperiled, ecologically relevant species, in different aquatic ecosystems. We are confident that this general framework is important for determining (1) the requirements and limitations of populations regarding abiotic variables, (2) biotic interactions (trophic and spatial) with native and introduced species, and (3) different anthropogenic stressors within and around the ecosystem. This knowledge will also allow understanding those aspects that contribute to the extirpation of populations and could help the restoration of the habitat and the reintroduction of extirpated species.