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    The role of southern red-backed voles, Myodes gapperi, and Peromyscus mice in the enzootic maintenance of Lyme disease spirochetes in North Dakota, USA.

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    Lyme disease has expanded into the Great Plains of the USA. To investigate local enzootic transmission, small mammals were trapped in two forested tracts in northeastern North Dakota during 2012 and 2013. Peromyscus mice and southern red-backed voles, Myodes gapperi, comprised over 90% of all mammals captured. One site was dominated by Peromyscus (79% of 100 mammals captured). At the other site, M. gapperi (59% of 107 mammals captured) was more abundant than Peromyscus (36%). Immature stages of two tick species parasitized small mammals: Dermacentor variabilis and Ixodes scapularis. Larval I. scapularis ectoparasitism was significantly higher on Peromyscus (81% infested; 3.7 larvae per infested mouse) than M. gapperi (47% infested; 2.6 larvae per infested vole) whereas larval and nymphal D. variabilis ectoparasitism were highest on M. gapperi. Over 45% of infested rodents were concurrently infested with both tick species. Testing engorged I. scapularis larvae from Peromyscus (n = 66) and M. gapperi (n = 20) yielded xenopositivity prevalence for Borrelia burgdorferi sensu lato (s.l.) in these rodents of 6% and 5%, respectively. Progeny of field collected M. gapperi were used to determine host infectivity for a local isolate of B. burgdorferi sensu stricto (s.s.). Five M. gapperi were injected with spirochetes, infested with pathogen-free I. scapularis larvae on days 10, 20, and 40 after infection, and engorged larvae molted to nymphs. Subsamples of nymphs were tested by PCR for B. burgdorferi s. s. DNA and yielded infection rates of 56% (n = 100 nymphs tested), 75% (n = 8) and 64% (n = 31), respectively. The remaining infected nymphs were fed on BALB/c Mus musculus mice and 7 d later, mice were euthanized, and tissues were cultured for B. burgdorferi s.s. Nymphs successfully transmitted spirochetes to 13 of 18 (72%) mice that were exposed to 1-5 infected ticks. Theoretical reservoir potentials - i.e., ability to generate B. burgdorferi infected nymphs - were compared between Peromyscus and M. gapperi. At one site, Peromyscus accounted for nearly all Borrelia-infected nymphs produced (reservoir potential value of 0.935). At the other site, the reservoir potentials for Peromyscus (0.566) and M. gapperi (0.434) were comparable. The difference was attributed to differences in the relative abundance of voles versus mice between sites and the higher level of ectoparasitism by larval I. scapularis on Peromyscus versus M. gapperi at both sites. The southern red-backed vole, M. gapperi, contributes to the enzootic maintenance of Lyme disease spirochetes in North Dakota and possibly other areas where this rodent species is abundant

    [Practical application of immunohistochemistry in pancreatic neuroendocrine neoplasms : Tips and pitfalls].

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    Pancreatic neuroendocrine neoplasms (PanNEN) are rather rare entities. Morphology, combined with immunohistochemistry, allows typing and grading, thereby leading therapeutic decisions. Depending on tumor stage and differential diagnosis, a broad diagnostic panel may be required. The present work summarizes the minimal diagnostic, prognostic, and predictive markers in PanNEN.Markers of choice for defining a neuroendocrine phenotype are synaptophysin, chromogranin A, and INSM1. The proliferation fraction Ki67 is indispensable for grading, while p53 and Rb1 can help in the differentiation from neuroendocrine carcinoma (NEC). Transcription factors, such as cdx2, TTF‑1, and Islet‑1, can indicate the site of a primary tumor in the setting of a cancer of unknown primary (CUP). DAXX/ATRX immunohistochemistry has mainly prognostic value. Molecular pathology studies currently have little practical value in the diagnosis of PanNEN.An important pitfall in routine diagnostics is the wide spectrum of differential diagnoses mimicking neuroendocrine neoplasms. An expanded immunohistochemical panel is strongly recommended in case of doubt

    Experimental vaccination by single dose sporozoite injection of blood-stage attenuated malaria parasites.

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    Malaria vaccination approaches using live Plasmodium parasites are currently explored, with either attenuated mosquito-derived sporozoites or attenuated blood-stage parasites. Both approaches would profit from the availability of attenuated and avirulent parasites with a reduced blood-stage multiplication rate. Here we screened gene-deletion mutants of the rodent parasite P. berghei and the human parasite P. falciparum for slow growth. Furthermore, we tested the P. berghei mutants for avirulence and resolving blood-stage infections, while preserving sporozoite formation and liver infection. Targeting 51 genes yielded 18 P. berghei gene-deletion mutants with several mutants causing mild infections. Infections with the two most attenuated mutants either by blood stages or by sporozoites were cleared by the immune response. Immunization of mice led to protection from disease after challenge with wild-type sporozoites. Two of six generated P. falciparum gene-deletion mutants showed a slow growth rate. Slow-growing, avirulent P. falciparum mutants will constitute valuable tools to inform on the induction of immune responses and will aid in developing new as well as safeguarding existing attenuated parasite vaccines

    The Ruminant Telomere-to-Telomere (RT2T) Consortium.

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    Telomere-to-telomere (T2T) assemblies reveal new insights into the structure and function of the previously 'invisible' parts of the genome and allow comparative analyses of complete genomes across entire clades. We present here an open collaborative effort, termed the 'Ruminant T2T Consortium' (RT2T), that aims to generate complete diploid assemblies for numerous species of the Artiodactyla suborder Ruminantia to examine chromosomal evolution in the context of natural selection and domestication of species used as livestock

    Deep Learning-based Modeling for Preclinical Drug Safety Assessment.

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    In drug development, assessing the toxicity of candidate compounds is crucial for successfully transitioning from preclinical research to early-stage clinical trials. Drug safety is typically assessed using animal models with a manual histopathological examination of tissue sections to characterize the dose-response relationship of the compound - a time-intensive process prone to inter-observer variability and predominantly involving tedious review of cases without abnormalities. Artificial intelligence (AI) methods in pathology hold promise to accelerate this assessment and enhance reproducibility and objectivity. Here, we introduce TRACE, a model designed for toxicologic liver histopathology assessment capable of tackling a range of diagnostic tasks across multiple scales, including situations where labeled data is limited. TRACE was trained on 15 million histopathology images extracted from 46,734 digitized tissue sections from 157 preclinical studies conducted on Rattus norvegicus. We show that TRACE can perform various downstream toxicology tasks spanning histopathological response assessment, lesion severity scoring, morphological retrieval, and automatic dose-response characterization. In an independent reader study, TRACE was evaluated alongside ten board-certified veterinary pathologists and achieved higher concordance with the consensus opinion than the average of the pathologists. Our study represents a substantial leap over existing computational models in toxicology by offering the first framework for accelerating and automating toxicological pathology assessment, promoting significant progress with faster, more consistent, and reliable diagnostic processes

    Emotional and interpersonal states following dialectical behavioral therapy in adolescent borderline personality disorder: A proof-of-concept ecological momentary assessment outcome study.

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    Objective: The effects of Dialectical Behavioral Therapy for Adolescents (DBT-A) on emotional and interpersonal instability were explored in adolescents exhibiting Borderline Personality Disorder (BPD) features, using ecological momentary assessment (EMA) to reduce recall bias.Method: N = 28 help-seeking female adolescents were enrolled, meeting ≥ 3 DSM-IV BPD criteria. BPD criteria, non-suicidal self-injury (NSSI), and depressive symptoms were examined pre- and post-DBT-A treatment (mean duration: 42.74 weeks, SD = 7.46). Participants maintained e-diaries pre- and post-treatment, hourly rating momentary affect, attachment to mother and best friend, and self-injury urges.Results: Interview-rated BPD symptoms decreased (χ²(1) = 5.66, p = .017), alongside reduced self-rated depression severity (χ²(1) = 9.61, p = .002). EMA data showed decreased NSSI urges (χ²(1) = 9.05, p = .003) and increased mother attachment (χ²(1) = 6.03, p = .014). However, mean affect, affective instability, mean attachment to the best friend, and attachment instability showed no significant change over time.Conclusion: DBT-A yielded limited evidence for altering momentary affective states and instability in adolescents based on EMA. Nevertheless, significant effects were observed in reducing NSSI urges and enhancing interpersonal dynamics during treatment, as assessed via EMA

    A climatology of Mediterranean cyclones and compound weather extremes

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    Mediterranean cyclones are the main driver of surface weather extremes in the Mediterranean region. In this work we establish a new procedure for the attribution of different types of meteorological extremes to Mediterranean cyclones, where we also distinguish the presence of different airflows (warm conveyor belts, dry intrusions) and fronts composing the structure of a cyclone. We apply the procedure to a dataset of rain-wind and wave-wind compound extremes extracted from ERA5 reanalysis in a recent climatological period, and show that the majority of weather compounds occurring in the Mediterranean area is indeed linked to the presence of a nearby cyclone. The association of compound rain-wind events with Mediterranean cyclones locally surpasses an 80% level, while interesting differences between transition seasons and winter are detected. Winter cyclones - generally stronger, larger and distinctively baroclinic - are associated with a higher compound density. The de-construction of the cyclone in airflows and fronts evidences a strong association of rain-wind compounds with regions of warm conveyor belt ascent, and of wave-wind compounds with regions of dry intrusion outflow

    Sri Lanka’s elusive freshwater spiny eel, Macrognathus pentophthalmos (Teleostei: Mastacembelidae)

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    This study focuses on Macrognathus pentophthalmos, one of the two freshwater spiny eel species in Sri Lanka, which was once abundant in lowland floodplains. However, since the 1980s, this species has experienced a significant population decline, the causes of which remain unknown. It is presently assessed as Critically Endangered in the National Red List. Here, we report on a juvenile and an adult M. pentophthalmos discovered in the dry zone lowlands of the island. Using the mitochondrial cytochrome oxidase subunit 1 marker, we reveal subtle genetic differences between M. pentophthalmos and its Indian congener, M. aral. Additionally, we delve into the historical records of M. pentophthalmos in Sri Lanka, tracing its decline, and suggest strategic hotspots for further investigation into its current status. This study aims to contribute insights into the enigmatic decline of this species while shedding light on its genetic relationships and proposing targeted areas for conservation efforts

    Unveiling the Role of Metal Ion Concentration versus Immune Sensitization in Orthodontic Patients-A Long-Term Prospective Evaluation.

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    Background: This longitudinal prospective study aimed to assess orthodontic patients' immune system response to metal ion release in saliva. Methods: Thirty adult patients (18-35 years) were equally divided into three groups: groups at the end (G1) and beginning (G2) of multibracket appliances (MBA) treatment and a non-treated control group (G3). Participants were evaluated at four timepoints within 21 days, with saliva samples being analyzed for metal ion concentrations and blood for the lymphocyte transformation test (LTT). Results: There were no significant differences between groups or timepoints for saliva. LTT analyses revealed hypersensitivity in one-third of all patients and 50% of G2 for nickel, with three developing sensitizations after MBA insertion. All nickel-sensitized patients exhibited varying elevated saliva nickel concentrations. The most nickel-sensitized patients had low ion saliva loads. In borderline nickel-sensitization cases, saliva ion concentrations were up to 20 times higher than the reference. Hypersensitivity to palladium, gold, and mercury was also observed. Conclusions: These findings indicate that increased MBA ion release was not inherently linked to the immune response (Type-IV sensitization), as reactions occurred even with ion levels below thresholds. This underlines the need for a comprehensive evaluation of the immune response to metal ion release in orthodontic patients

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