Репозиторий Университета

© 2019, International League of Associations for Rheumatology (ILAR). Abstract: Streptococcus is well associated with a myriad of inflammatory diseases. Among others, this bacterium is linked to the triggering of psoriasis and to post-streptococcal reactive arthritis (PSRA), an arthritis which is typically confined to peripheral joints. Three patients who developed acute psoriatic spondyloarthritis (SpA) following a recent streptococcal infection are described in this article. We searched the existing literature for cases of axial involvement in PSRA and reviewed the association between streptococcal infection and psoriasis or psoriatic arthritis )PsA). In all patients, psoriatic SpA occurred within 7–10 days of a confirmed streptococcal infection. The main presenting syndrome was inflammatory back pain with evidence of acute axial spondyloarthritis on magnetic resonance imaging. One patient had guttate psoriasis, the second patient developed pustular psoriasis, and the third patient had exacerbation of pustular palmoplantar psoriasis. Two patients required treatment with tumor necrosis factor alpha (TNF-α) blockers. Axial involvement in PSRA is very rare. A potential association of streptococcal infection and development of PsA has been explored in several articles. However, to the best of our knowledge, acute psoriatic SpA as a manifestation of PSRA has yet to be described. Acute psoriatic SpA should be considered in the differential diagnosis of new-onset inflammatory back pain followed by psoriasis in young adults who had a recent throat infection. Key Points: • Our case series describes three cases of acute psoriatic spondyloarthritis that occurred within 7–-10 days of a confirmed streptococcal infection and progressed to full blown chronic disease. • Acute psoriatic spondyloarthritis as a manifestation of post streptococcal reactive arthritis should be considered in the differential diagnosis of new onset inflammatory back pain followed by psoriasis in young adults who had a recent throat infection.

© 2019 Society for Vascular Surgery Objective: This study aimed to evaluate the impact of gravity, reservoir size, and competence of the ostial valve on venous reflux in different body positions. Methods: Our study included 61 lower limbs with primary incompetence of the great saphenous vein (GSV). The diameter of the GSV and its cross-sectional area, time-averaged mean velocity (TAMEAN), and reflux time (RT) were measured with duplex ultrasound with pulsed wave Doppler. Reflux volume (RV) and reflux volume flow rate (Q) were calculated. The measurements were carried out in three body positions: horizontal, A; seated upright with stretched legs, B; and vertical, C. Distal automatic cuff compression-decompression (120 mm Hg) was used as a provocation maneuver. Results: There was 100% occurrence of reflux in the patient positions B and C. Reflux was observed in 91.8% of cases in position A. All reflux parameters (TAMEAN, RT, Q, RV) and the size of the vein were significantly different in the three studied positions. The patient's height did not influence the magnitude of change in reflux parameters. All reflux parameters increased more significantly when the position changed from A to B than from B to C (TAMEAN, +103% and +37%; GSV diameter, +33% and +5%; RV, +408% and +65%, respectively). Conclusions: Observed positional changes in reflux parameters suggest that gravitational forces are not a sole explanation for reflux flow in incompetent GSV. It is likely that the gravitational effect on venous flow is mediated by the changes in vein diameter and the total volume of the venous reservoir of the leg.

© 2019 Elsevier Ltd Activated protein C (APC) exerts diverse cell signaling pathways which results in multiple distinct cytoprotective actions. These include anti-apoptotic and anti-inflammatory activities and stabilization of endothelial and epithelial barriers. We studied the ability of APC to inhibit the leakage and the growth of newly formed as well as pre-existing choroidal neovascularization (CNV) and examined the ability of APC to stabilize the Retinal Pigmented Epithelium (RPE). We explored the contribution of Tie2 receptor to the protective effects of APC. CNV was induced by laser photocoagulation in C57BL/6J mice. APC was injected intravitreally immediately or 7 days after CNV induction. Neovascularization was evaluated on RPE-choroidal flatmounts using FITC-dextran perfusion and CD31 immunofluorescence. CNV leakage was measured by fluorescein angiography (FA). The ability of APC to stabilize the RPE barrier was evaluated in-vitro by dextran permeability and zonula occludens 1 (ZO1) immunostaining. Tie2 blocking was induced in-vivo by intraperitoneal injection of Tie2 kinase inhibitor and in-vitro by incubation with anti Tie2 antibodies. APC treatment dramatically inhibited the generation of newly formed CNV leakage sites and reversed leakage in 85% of the pre-existing CNV leaking sites. In RPE cell culture, APC induced translocation of ZO1 to the cell membrane, accompanied by reduction in permeability of the monolayer. Inhibition of Tie2 significantly decreased APC protective activities in both the mouse model and the RPE cell culture. Our results show that APC treatment significantly inhibits the leakage and growth of newly formed, as well as pre-existing CNV, and its protective activities are partially mediated via the Tie2 receptor. The data suggest that APC should be further investigated as a possible effective treatment for CNV.

© 2019 Elsevier B.V. To date, laser-induced forward transfer (LIFT) is one of the most developing areas in bioprinting. It is based on a precise nozzle-free laser-assisted hydrogel microdroplet transfer. Although this technique was first mentioned in the 1980s, it started to gain popularity in biomedicine only a decade ago. While the interest in LIFT bioprinting is constantly growing, it is essential to provide a framework of its possibilities and limitations. This review aims to facilitate the search for a common language between physicists and biologists and thus become a short guide to using LIFT technology for biomedicine. Here, we compared various points such as lasers, bioinks components, collector substrate, post-treatment, and printing processes that are crucial for LIFT bioprinting and applied in published studies on it. The core of this review is the discussion of biological and physical aspects to fabricate tissues and organs and the not-known difficulties that can be encountered during the laser printing process and were not given sufficient attention earlier.

© 2019, European Society of Radiology. Objectives: Invasive treatment of tumors adjacent to large hepatic vessels is a continuous clinical challenge. The primary aim of this study was to examine the feasibility of ablating liver tissue adjacent to large hepatic and portal veins with magnetic resonance imaging–guided high-intensity focused ultrasound (MRgHIFU). The secondary aim was to compare sonication data for ablations performed adjacent to hepatic veins (HV) versus portal veins (PV). Materials and methods: MRgHIFU ablations were performed in six male land swine under general anesthesia. Ablation cells of either 4 or 8 mm diameter were planned in clusters (two/animal) adjacent either to HV (n = 6) or to PV (n = 6), with diameter ≥ 5 mm. Ablations were made using 200 W and 1.2 MHz. Post-procedure evaluation was made on contrast-enhanced MRI (T1w CE-MRI), histopathology, and ablation data from the HIFU system. Results: A total of 153 ablations in 81 cells and 12 clusters were performed. There were visible lesions with non-perfused volumes in all animals on T1w CE-MRI images. Histopathology showed hemorrhage and necrosis in all 12 clusters, with a median shortest distance to vessel wall of 0.4 mm (range 0–2.7 mm). Edema and endothelial swelling were observed without vessel wall rupture. In 8-mm ablations (n = 125), heat sink was detected more often for HV (43%) than for PV (19%; p = 0.04). Conclusions: Ablations yielding coagulative necrosis of liver tissue can be performed adjacent to large hepatic vessels while keeping the vessel walls intact. This indicates that perivascular tumor ablation in the liver is feasible using MRgHIFU. Key Points: • High-intensity focused ultrasound ablation is a non-invasive treatment modality that can be used for treatment of liver tumors. • This study shows that ablations of liver tissue can be performed adjacent to large hepatic vessels in an experimental setting. • Liver tumors close to large vessels can potentially be treated using this modality.

© 2019 by author(s) and VsI Entrepreneurship and Sustainability Center. Corruption in various sectors causes serious damage not only to individual economies, countries, and regions but also to humanity as a whole. This paper analyzes the state of corruption in the Republic of Tatarstan, the manifestations of which restrain the development of the Republic, and presents the results of a pilot sociological study that demonstrate changes in the perception of problems of corruption in society. The sustainable development of a region is influenced by various economic and social factors. The results of this research show that one of these factors is corruption, which is often used as a tool for managing territories at various levels. It is a serious obstacle to the achievement of continuous sustainable development of a region, as it impedes the building of harmonious relations between state, government, society, and business. Sustainable development of a region can be described as a system and as a process. In this study, “sustainable development” refers to the process in which various stakeholder interactions take place that influence the established order of relations in the region. The findings suggest that when assessing the effectiveness of a region’s sustainable development, the level of corruption should be considered as an indicator of its stability. Some measures were proposed to improve the organization of anti-corruption work in the Republic of Tatarstan for leveling social tensions in society.

© 2019 Elsevier B.V. Lassa fever is a severe viral hemorrhagic illness caused by Lassa virus. Based on estimates, the number of LASV infections ranges from 300,000 to 500,000 cases in endemic areas with a fatality rate of 1%. Development of fast and sensitive tools for the control and prevention of Lassa virus infection as well as for clinical diagnostics of Lassa fever are crucial. Here we reported development and evaluation of a one-step quantitative RT-qPCR assay for the Lassa virus detection – LASV-Fl. This assay is suitable for the detection of lineages I-IV of Lassa virus. The limit of detection of the assay ranged from 103 copies/ml to 105 copies/ml and has 96.4% diagnostic sensitivity, whereas analytical and diagnostic specificities both were 100%. Serum, whole blood and tissue are suitable for use with the assay. The assay contains all the necessary components to perform the analysis, including an armored positive control (ARC+) and an armored internal control (IC). The study was done during the mission of specialized anti-epidemic team of the Russian Federation (SAET) in the Republic of Guinea in 2015-2018. Based on sequencing data, LASV-specific assay was developed using synthetic MS2-phage-based armored RNA particles, RNA from Lassa virus strain Josiah, and further, evaluated in field conditions using samples from patients and Mastomys natalensis rodents.

© 2019, Pediatria Ltd. All rights reserved. The article presents main pathogenetic factors of enuresis formation in children without malformations and diseases of the spine and spinal cord. 48 children were treated with cognitive and behavioral methods, based on formation of an age-related physiological regimen of fluid intake and urination. The drug of choice for drug therapy was desmopressin (Antikva Rapid) 120 mcg, efficacy was evaluated after 6 weeks of treatment by the number of night bedwetting per week. If its number was reduced by 50% or more from the original, then the drug dose remained the same. For children, whose proportion of night bedwetting was more than 50%, the desmopressin dose was increased by 60 mcg/ day. The total treatment course was 3 months. Treatment efficacy at the end of the course was evaluated by the “dry” period duration. If it was less than 14 days, a similar repeat course was planned. A correlation was found between the volume of nocturnal diuresis (ND) and the number of enuresis episodes per week, a decrease of these indicators by 32% at the stage of 1,5-month treatment and by 67% at the end of 3-month treatment was noted. DD showed a statistically significant increase, and ND a statistically significant decrease following the results of 1,5 and 3 months of treatment. After a 3-month course, a dry period of 14 days was observed in 16 children (33%). 2/3 of patients (67%) required a second course of treatment.

© 2019 Here we report that trypanosomatid flagellates of the genus Blastocrithidia possess catalase. This enzyme is not phylogenetically related to the previously characterized catalases in other monoxenous trypanosomatids, suggesting that their genes have been acquired independently. Surprisingly, Blastocrithidia catalase is less enzymatically active, compared to its counterpart from Leptomonas pyrrhocoris, posing an intriguing biological question why this gene has been retained in the evolution of trypanosomatids.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Ovarian cancer is fifth in the rankings of cancer deaths among women, and accounts for more deaths than any other gynecological malignancy. Despite some improvement in overall-(OS) and progression-free survival (PFS) following surgery and first-line chemotherapy, there is a need for development of novel and more effective therapeutic strategies. In this mini review, we provide a summary of the current landscape of the clinical use of tyrosine kinase inhibitors (TKIs) and mechanistic target of rapamycin (mTOR) inhibitors in ovarian cancer. Emerging data from phase I and II trials reveals that a combinatorial treatment that includes TKIs and chemotherapy agents seems promising in terms of PFS despite some adverse effects recorded; whereas the use of mTOR inhibitors seems less effective. There is a need for further research into the inhibition of multiple signaling pathways in ovarian cancer and progression to phase III trials for drugs that seem most promising.

© 2019 by the authors. Background: Vitamin D insuffciency is prevalent among athletes, and it can negatively affect physical performance. At the same time, most of the available data were obtained from untrained individuals of various ages, and published studies performed in athletes led to contradictory conclusions. Methods: This cohort prospective study examined the serum concentration of 25-hydroxycalciferol (25(OH)D) and its association with running speed and muscle power in 131 young football players (mean age 15.6 ± 2.4 years). Results: 25(OH)D levels were below reference in 42.8% (serum 25(OH)D <30 ng/mL) and above reference in 30.5% of the participants (serum 25(OH)D 61-130 ng/mL). A comparison of the results of 5, 15, and 30 m sprint tests and the standing long jump test found no statistically significant differences between the two groups. Athletes from the 25(OH)D-insuffcient group were treated with 5000 IU cholecalciferol supplement daily for 60 days. After the treatment, the 25(OH)D concentration increased by 79.2% and was within reference in 84% of the treated athletes (serum 25(OH)D 30-60 ng/mL). Testing was repeated after the end of treatment, and a statistically significant increase in the results of the 5, 15, and 30 m sprint tests was observed (Cohen’s d was 0.46, 0.33, and 0.34, respectively), while the results of the standing long jump test remained unchanged. Body height, body weight, and lean body mass of the football players also increased. Conclusions: These findings indicate that there is likely no correlation between serum levels of 25(OH)D, muscle power, and running speed in young professional football players, and the changes observed post-treatment might have been caused by changes in the anthropometric parameters. During the study, all the anthropometric parameters changed, but the amount of lean body mass only correlated with the results of the 5 m sprint.

© 2019, Pediatria Ltd. All rights reserved. Brain–lung–thyroid syndrome (BLTS) is a rare genetic disease associated with mutations in the NKX2.1 gene encoding thyroid transcription factor 1. The most common manifestations of this syndrome are benign hereditary chorea, hypothyroidism and respiratory distress syndrome, however, mutations in the NKX2.1 gene can also cause other pathologies of nervous, respiratory systems and thyroid gland. The article describes 4 patients with mutations in the NKX2.1 gene observed by authors. Based on the analysis of the observations of 168 patients with BLTS presented in the world literature from 1998 to 2019, current information on the genetics, pathogenesis, clinical X-ray manifestations, outcomes and treatment of the syndrome are summarized.

© 2019 European Association of Urology In this review, we investigated the treatment options for primary urethral cancer. While organ-confined disease can be managed with local resection, growth beyond the organ calls for a combination of different treatment modalities, such as surgery, chemotherapy, and radiotherapy, to improve the survival of patients.

© 2019 John Wiley  &  Sons Ltd Background: Human milk (HM) transforming growth factor beta (TGF-β) is critical for inflammation regulation and oral tolerance promotion. Previous reports suggested that variations in HM TGF-β levels are associated with allergic outcomes. Objective: We undertook a systematic review (PROSPERO 2017 CRD42017069920) to reassess the evidence on the relationships between HM TGF-β and allergic outcomes in children. Methods: Electronic bibliographic databases (MEDLINE, EMBASE and Cochrane Library) were systematically searched. Two independent reviewers screened reference lists, extracted the data and assessed risk of bias using the National Institute for Clinical Excellence methodological checklist. Results: A total of 21 studies were identified. Sixteen studies assessed relationships between HM TGF-β and risk of eczema; 14, allergic sensitization; nine, wheezing/asthma; six, food allergy; three, allergic rhinitis/conjunctivitis. Five cohorts (5/18, 28%) reported a protective effect of TGF-β1, while 3 (3/10, 30%) suggested increased risk of allergic outcomes development and 1 (1/10, 10%), a protective effect of TGF-β2 on eczema. Meta-analysis was not possible due to significant heterogeneity in methodology, age of outcome assessment and differing statistical approaches. 71% (15/21) of studies carried a high risk of bias. Conclusion and clinical relevance: In contrast with previous findings, we did not find strong evidence of associations between HM TGF-β and allergic outcomes. Differences in studies' methodology and outcomes do not allow unconditional rejection or acceptance of the hypothesis that HM TGF-β influences the risk of allergy development. Future studies on diverse populations employing standardized methods, accurate phenotyping of outcomes and evaluation of the effect of TGF-β in combination with other HM immune markers, microbiome and oligosaccharides are required.

© 2019 Elsevier GmbH Background: The objective of the study was to assess hair trace element and mineral content in children undergoing WFP UN and the governmental programs of school nutrition in Tajikistan. Methods: WFP program included provision or wheat flour fortified with micronutrients including Fe and Zn, and iodized salt, whereas within the governmental program hot meals were provided. A total of 202 children studying in schools that were not (Type 1, n = 100) or were involved in dietary intervention programs (Type 2, n = 102). Food and hair trace element content was assessed using ICP-MS. Results: Daily intake of Fe, I, Zn, B, Co, Mg, Si, and Sr in Type 2 schools was more than 2.5, 12, 4, 2.9, 2.6, 2, 3, and 2-fold higher than that in Type 1 schools. Correspondingly, anthropometric parameters in children from Type 2 schools exceeded the control values. Surprisingly, no significant difference in hair iodine levels was detected. Hair analysis demonstrated a significant increase in hair Ca, Mg, Na, Co, Cr, Cu, Fe, Li, Mn, Se, V, Zn content. Certain toxic elements including Al, As, and Be were also characterized by an increase in Type 2 schools. At the same time, nutritional intervention was associated with a significant decrease in hair B, Hg, and Sn levels. Conclusions: Nutritional intervention within WFP and the governmental program was effective in increasing essential trace element supply in Tajik schoolchildren. However, further studies including a detailed assessment of nutritional and health status with a special focus on iodine and thyroid functioning are required.

© 2019, The Author(s). Purpose: To assess the accuracy of [68Ga]-PSMA-11 PET/CT or [68Ga]-PSMA-11 PET/MRI (PSMA-11 PET/CT(MRI)) for lymph node (LN) staging using salvage LN dissection (SLND) in patients with biochemical recurrence (BCR) after radical prostatectomy (RP). Patients and methods: In a prospective study, 65 consecutive patients who developed BCR after RP underwent SLND after PSMA-11 PET/CT(MRI) between 2014 and 2018. Extended SLND up to the inferior mesenteric artery was performed in all patients. Regional and template-based correlations between the presence of LN metastases on histopathology and whole-body PSMA-11 PET/CT(MRI) results were evaluated. The diagnostic accuracy of PSMA-11 PET/CT(MRI) was also evaluated in relation to PSA level at the time of SLND. Results: The median age of the patients at the time of SLND was 65 years (IQR 63–69 years) and the median PSA level was 1.4 ng/ml (IQR 0.8–2.9 ng/ml). Before SLND, 50 patients (77%) had additional therapy after RP (26.2% androgen-deprivation therapy and 50.8% radiotherapy). The median number of LNs removed on SLND was 40 (IQR 33–48) and the median number of positive nodes was 4 (IQR 2–6). LN metastases were seen in 13.8% of resected LNs (317 of 2,292). LNs positive on PSMA-11 PET/CT(MRI) had a median diameter of 7.2 mm (IQR 5.3–9 mm). Metastatic LNs in regions negative on PSMA-11 PET had a median diameter of 3.4 mm (IQR 2.1–5.4 mm). In a regional analysis, the sensitivity of PSMA-11 PET/CT(MRI) ranged from 72% to 100%, and the specificity from 96% to 100%. Region-specific positive and negative predictive values ranged from 95% to 100% and 93% to 100%, respectively. Conclusion: PSMA-11 PET/CT(MRI) has a very good performance for the identification of LN metastases in patients with BCR after RP. The high diagnostic accuracy in the regional and subregional analyses demonstrates the potential of this approach to enable a region-directed instead of a complete bilateral therapeutic intervention. The performance of PSMA-11 PET/CT(MRI) is dependent on the PSA level and the size of the metastatic deposit.

© 2019 The Journal of Rheumatology. All rights reserved. Objective. To determine whether neutropenia is associated with increased risk for infection in patients with systemic juvenile idiopathic arthritis (sJIA) and polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with tocilizumab (TCZ). Methods. Data up to Week 104 from 2 phase III trials of intravenous TCZ in sJIA (n = 112; ClinicalTrials.gov, NCT00642460) and pcJIA (n = 188; ClinicalTrials.gov, NCT00988221) were pooled. Worst common toxicity criteria grade and lowest observed absolute neutrophil count (ANC) were identified for each patient. Associations between patient characteristics and lowest observed ANC were tested using univariate regression analysis. Infection and serious infection rates per 100 patient-years (PY) in periods associated with grades 1/2 and 3/4 neutrophil counts were compared with rates associated with normal neutrophil counts. Results.ANC decreased to grade ≥ 3 in 25.0% and 5.9% of sJIA and pcJIA patients, respectively, and decreases were transient. Young age (p = 0.047) and methotrexate use (p = 0.012) were positively associated with neutropenia in patients with sJIA but not in patients with pcJIA. The rate of serious infections in patients with sJIA (10.9/100 PY; 95% CI 6.8-16.5) tended to be higher than in patients with pcJIA (5.2/100 PY; 95% CI 3-8.5). No increase in rates of serious or nonserious infections was observed during periods of neutropenia in either trial. Conclusion. Patients with JIA treated with TCZ experienced transient neutropenia that was not associated with an increased number of infections.

© 2019 The Author(s). Background: Cobalamin metabolism disorders are rare, inherited diseases which cause megaloblastic anaemia and other clinical manifestations. Early diagnosis of these conditions is essential, in order to allow appropriate treatment as early as possible. Case presentation: Here we report the case of a patient who was apparently healthy until the age of 20, when she presented with impaired renal function and normocytic anaemia. At the age of 34, when her first pregnancy resulted in an intrauterine death of a morphologically normal growth-restricted foetus, she was diagnosed with homocystinuria and methylmalonic aciduria due to cyanocobalamin C (cblC) defect, which was confirmed by molecular investigation. Consequently, hydroxocobalamin was administered to correct homocysteine plasma levels. This treatment was efficacious in lowering homocysteine plasma levels and restored anaemia and renal function. During a second pregnancy, the patient was also administered a prophylactic dose of low molecular -weight heparin. The pregnancy concluded with a full-term delivery of a healthy male. Conclusions: This case emphasises the importance of awareness and appropriate management of rare metabolic diseases during pregnancy. We suggest that women with late-onset cblC defect can have a positive pregnancy outcome if this metabolic disease is treated adequately.

© Copyright © 2019 Lechermeier, Zimmer, Lüffe, Lesch, Romanos, Lillesaar and Drepper. The transport of glucose across the cell plasma membrane is vital to most mammalian cells. The glucose transporter (GLUT; also called SLC2A) family of transmembrane solute carriers is responsible for this function in vivo. GLUT proteins encompass 14 different isoforms in humans with different cell type-specific expression patterns and activities. Central to glucose utilization and delivery in the brain is the neuronally expressed GLUT3. Recent research has shown an involvement of GLUT3 genetic variation or altered expression in several different brain disorders, including Huntington’s and Alzheimer’s diseases. Furthermore, GLUT3 was identified as a potential risk gene for multiple psychiatric disorders. To study the role of GLUT3 in brain function and disease a more detailed knowledge of its expression in model organisms is needed. Zebrafish (Danio rerio) has in recent years gained popularity as a model organism for brain research and is now well-established for modeling psychiatric disorders. Here, we have analyzed the sequence of GLUT3 orthologs and identified two paralogous genes in the zebrafish, slc2a3a and slc2a3b. Interestingly, the Glut3b protein sequence contains a unique stretch of amino acids, which may be important for functional regulation. The slc2a3a transcript is detectable in the central nervous system including distinct cellular populations in telencephalon, diencephalon, mesencephalon and rhombencephalon at embryonic and larval stages. Conversely, the slc2a3b transcript shows a rather diffuse expression pattern at different embryonic stages and brain regions. Expression of slc2a3a is maintained in the adult brain and is found in the telencephalon, diencephalon, mesencephalon, cerebellum and medulla oblongata. The slc2a3b transcripts are present in overlapping as well as distinct regions compared to slc2a3a. Double in situ hybridizations were used to demonstrate that slc2a3a is expressed by some GABAergic neurons at embryonic stages. This detailed description of zebrafish slc2a3a and slc2a3b expression at developmental and adult stages paves the way for further investigations of normal GLUT3 function and its role in brain disorders.

© 2019 National Academy of Sciences. All rights reserved. Shrews, insectivorous small mammals, pertain to an ancient mammalian order. We screened 693 European and African shrews for hepatitis B virus (HBV) homologs to elucidate the enigmatic genealogy of HBV. Shrews host HBVs at low prevalence (2.5%) across a broad geographic and host range. The phylogenetically divergent shrew HBVs comprise separate species termed crowned shrew HBV (CSHBV) and musk shrew HBV (MSHBV), each containing distinct genotypes. Recombination events across host orders, evolutionary reconstructions, and antigenic divergence of shrew HBVs corroborated ancient origins of mammalian HBVs dating back about 80 million years. Resurrected CSHBV replicated in human hepatoma cells, but human- and tupaia-derived primary hepatocytes were resistant to hepatitis D viruses pseudotyped with CSHBV surface proteins. Functional characterization of the shrew sodium taurocholate cotransporting polypeptide (Ntcp), CSHBV/MSHBV surface peptide binding patterns, and infection experiments revealed lack of Ntcp-mediated entry of shrew HBV. Contrastingly, HBV entry was enabled by the shrew Ntcp. Shrew HBVs universally showed mutations in their genomic preCore domains impeding hepatitis B e antigen (HBeAg) production and resembling those observed in HBeAg-negative human HBV. Deep sequencing and in situ hybridization suggest that HBeAg-negative shrew HBVs cause intense hepatotropic monoinfections and low within-host genomic heterogeneity. Geographical clustering and low MSHBV/CSHBV-specific seroprevalence suggest focal transmission and high virulence of shrew HBVs. HBeAg negativity is thus an ancient HBV infection pattern, whereas Ntcp usage for entry is not evolutionarily conserved. Shrew infection models relying on CSHBV/MSHBV revertants and human HBV will allow comparative assessments of HBeAg-mediated HBV pathogenesis, entry, and species barriers.