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1.
Nature ; 626(8001): 1116-1124, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38355802

RESUMO

Transposable elements (TEs) are a major constituent of human genes, occupying approximately half of the intronic space. During pre-messenger RNA synthesis, intronic TEs are transcribed along with their host genes but rarely contribute to the final mRNA product because they are spliced out together with the intron and rapidly degraded. Paradoxically, TEs are an abundant source of RNA-processing signals through which they can create new introns1, and also functional2 or non-functional chimeric transcripts3. The rarity of these events implies the existence of a resilient splicing code that is able to suppress TE exonization without compromising host pre-mRNA processing. Here we show that SAFB proteins protect genome integrity by preventing retrotransposition of L1 elements while maintaining splicing integrity, via prevention of the exonization of previously integrated TEs. This unique dual role is possible because of L1's conserved adenosine-rich coding sequences that are bound by SAFB proteins. The suppressive activity of SAFB extends to tissue-specific, giant protein-coding cassette exons, nested genes and Tigger DNA transposons. Moreover, SAFB also suppresses LTR/ERV elements in species in which they are still active, such as mice and flies. A significant subset of splicing events suppressed by SAFB in somatic cells are activated in the testis, coinciding with low SAFB expression in postmeiotic spermatids. Reminiscent of the division of labour between innate and adaptive immune systems that fight external pathogens, our results uncover SAFB proteins as an RNA-based, pattern-guided, non-adaptive defence system against TEs in the soma, complementing the RNA-based, adaptive Piwi-interacting RNA pathway of the germline.


Assuntos
Elementos de DNA Transponíveis , Íntrons , Precursores de RNA , Splicing de RNA , RNA Mensageiro , Animais , Humanos , Masculino , Camundongos , Elementos de DNA Transponíveis/genética , Drosophila melanogaster/genética , Éxons/genética , Genoma/genética , Íntrons/genética , Especificidade de Órgãos/genética , RNA de Interação com Piwi/genética , RNA de Interação com Piwi/metabolismo , Precursores de RNA/genética , Precursores de RNA/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espermátides/citologia , Espermátides/metabolismo , Splicing de RNA/genética , Testículo , Meiose
2.
Blood ; 143(14): 1391-1398, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38153913

RESUMO

ABSTRACT: Distinct diagnostic entities within BCR::ABL1-positive acute lymphoblastic leukemia (ALL) are currently defined by the International Consensus Classification of myeloid neoplasms and acute leukemias (ICC): "lymphoid only", with BCR::ABL1 observed exclusively in lymphatic precursors, vs "multilineage", where BCR::ABL1 is also present in other hematopoietic lineages. Here, we analyzed transcriptomes of 327 BCR::ABL1-positive patients with ALL (age, 2-84 years; median, 46 years) and identified 2 main gene expression clusters reproducible across 4 independent patient cohorts. Fluorescence in situ hybridization analysis of fluorescence-activated cell-sorted hematopoietic compartments showed distinct BCR::ABL1 involvement in myeloid cells for these clusters (n = 18/18 vs n = 3/16 patients; P < .001), indicating that a multilineage or lymphoid BCR::ABL1 subtype can be inferred from gene expression. Further subclusters grouped samples according to cooperating genomic events (multilineage: HBS1L deletion or monosomy 7; lymphoid: IKZF1-/- or CDKN2A/PAX5 deletions/hyperdiploidy). A novel HSB1L transcript was highly specific for BCR::ABL1 multilineage cases independent of HBS1L genomic aberrations. Treatment on current German Multicenter Study Group for Adult ALL (GMALL) protocols resulted in comparable disease-free survival (DFS) for multilineage vs lymphoid cluster patients (3-year DFS: 70% vs 61%; P = .530; n = 91). However, the IKZF1-/- enriched lymphoid subcluster was associated with inferior DFS, whereas hyperdiploid cases showed a superior outcome. Thus, gene expression clusters define underlying developmental trajectories and distinct patterns of cooperating events in BCR::ABL1-positive ALL with prognostic relevance.


Assuntos
Proteínas de Fusão bcr-abl , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Doença Aguda , Deleção Cromossômica , Proteínas de Fusão bcr-abl/genética , Genômica , Hibridização in Situ Fluorescente , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética
3.
Clin Chem ; 70(1): 250-260, 2024 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-37624932

RESUMO

BACKGROUND: Molecular brain tumor diagnosis is usually dependent on tissue biopsies or resections. This can pose several risks associated with anesthesia or neurosurgery, especially for lesions in the brain stem or other difficult-to-reach anatomical sites. Apart from initial diagnosis, tumor progression, recurrence, or the acquisition of novel genetic alterations can only be proven by re-biopsies. METHODS: We employed Nanopore sequencing on cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) and analyzed copy number variations (CNV) and global DNA methylation using a random forest classifier. We sequenced 129 samples with sufficient DNA. These samples came from 99 patients and encompassed 22 entities. Results were compared to clinical diagnosis and molecular analysis of tumor tissue, if available. RESULTS: 110/129 samples were technically successful, and 50 of these contained detectable circulating tumor DNA (ctDNA) by CNV or methylation profiling. ctDNA was detected in samples from patients with progressive disease but also from patients without known residual disease. CNV plots showed diagnostic and prognostic alterations, such as C19MC amplifications in embryonal tumors with multilayered rosettes or Chr.1q gains and Chr.6q losses in posterior fossa group A ependymoma, respectively. Most CNV profiles mirrored the profiles of the respective tumor tissue. DNA methylation allowed exact classification of the tumor in 22/110 cases and led to incorrect classification in 2/110 cases. Only 5/50 samples with detected ctDNA contained tumor cells detectable through microscopy. CONCLUSIONS: Our results suggest that Nanopore sequencing data of cfDNA from CSF samples may be a promising approach for initial brain tumor diagnostics and an important tool for disease monitoring.


Assuntos
Neoplasias Encefálicas , Ácidos Nucleicos Livres , Sequenciamento por Nanoporos , Humanos , Ácidos Nucleicos Livres/genética , Variações do Número de Cópias de DNA , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Mutação
4.
BMC Psychiatry ; 24(1): 194, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459520

RESUMO

BACKGROUND: This controlled pilot study investigates the effect of the combined use of cognitive restructuring (CR) and imagery rescripting (IR) compared to treatment as usual among inpatients with moderate and severe depression. Alongside expert ratings and self-report tools, fitness wristbands were used as an assessment tool. METHODS: In addition to the standard inpatient care (SIC) program, 33 inpatients with moderate and severe depression were randomly assigned to an intervention group (two sessions of IR and CR) or an active treatment-as-usual (TAU) control group (two sessions of problem-solving and build-up of positive activity). Depression severity was assessed by the Hamilton Depression Rating Scale-21 (HDRS-21), the Beck Depression Inventory-II (BDI-II), and as a diagnostic adjunct daily step count via the Fitbit Charge 3™. We applied for analyses of HDRS-21 and BDI-II, 2 × 2 repeated-measures analysis of variance (ANOVA), and an asymptotic Wilcoxon test for step count. RESULTS: The main effect of time on both treatments was η2 = .402. Based on the data from the HDRS-21, patients in the intervention group achieved significantly greater improvements over time than the TAU group (η2 = .34). The BDI-II data did not demonstrate a significant interaction effect by group (η2 = .067). The daily hourly step count for participants of the intervention group was significantly higher (r = .67) than the step count for the control group. CONCLUSIONS: The findings support the utilization of imagery-based interventions for treating depression. They also provide insights into using fitness trackers as psychopathological assessment tools for depressed patients. TRIAL REGISTRATION: The trial is registered at the German Clinical Trials Register (Deutsches Register Klinischer Studien) under the registration number: DRKS00030809.


Assuntos
Terapia de Reestruturação Cognitiva , Transtorno Depressivo Maior , Humanos , Depressão/terapia , Depressão/psicologia , Pacientes Internados , Transtorno Depressivo Maior/terapia , Projetos Piloto , Resultado do Tratamento
5.
J Arthroplasty ; 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38437886

RESUMO

BACKGROUND: In patients who have hip fractures, treatment within 24 hours reduces mortality and complication rates. A similar relationship can be assumed for patients who have hip periprosthetic femoral fractures (PPFs) owing to the similar baseline characteristics of the patient populations. This monocentric retrospective study aimed to compare the complication and mortality rates in patients who had hip PPF treated within and after 24 hours. METHODS: In total, 350 consecutive patients who had hip PPF in a maximum-care arthroplasty and trauma center between 2006 and 2020 were retrospectively evaluated. The cases were divided into 2 groups using a time to surgery (TTS) of 24 hours as the cutoff value. The primary outcome variables were operative and general complications as well as mortalities within 1 year. RESULTS: Overall, the mean TTS was 1.4 days, and the 1-year mortality was 14.6%. The TTS ≤ 24 hours (n = 166) and TTS > 24 hours (n = 184) groups were comparable in terms of baseline characteristics and comorbidities. Surgical complications were equally frequent in the 2 groups (16.3 versus 15.2%, P = .883). General complications occurred significantly more often in the late patient care group (11.4 versus 28.3%, P < .001). In addition, the 30-day mortality (0.6 versus 5.5%, P = .012), and 1-year mortality (8.3 versus 20.5%, P = .003) rates significantly increased in patients who had TTS > 24 hours. Cox regression analysis yielded a hazard ratio of 4.385 (P < .001) for the TTS > 24 hours group. CONCLUSIONS: Prompt treatment is required for patients who have hip PPF to reduce mortality and overall complications.

6.
Eur J Orthop Surg Traumatol ; 34(1): 119-126, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37358732

RESUMO

PURPOSE: Periprosthetic femoral fractures (PFF) according to type Vancouver C are less common and outcome is limited reported. Therefore, we conducted this retrospective single center study. METHODS: We performed analysis of patients who underwent open reduction and internal fixation (ORIF) with locking plates for PPF occurring distally of a primary standard hip stem. Data on demographics, revisions, fracture patterns, and mortality were evaluated. At least two years after operation, we examined outcome using the Parker and Palmer mobility score. Primary aim of this study was revision, outcome and mortality. Secondary aim was evaluation of fracture subtypes within type Vancouver C fractures. RESULTS: Between 2008 and 2020, 383 patients with periprosthetic femoral fracture after hip replacement were surgically treated according to our database. Among them, 40 patients (10.4%) with type Vancouver C fractures were enrolled for this study. The mean patient age was 81.5 years (59-94) at the time of fracture. Thirty-three patients were women, and 22 fractures were on the left side. Without exception, locking plates were used. The 1-year mortality rate for the sample was 27.5% (n = 11). Three revisions (7.5%) were performed for plate breakage. Rate of infection and non-union was zero. Three different fracture patterns were assessed: (1) transverse or oblique fractures below the tip of the stem (n = 9); (2) spiral-shaped fractures within the diaphysis (n = 19); and (3) burst fractures at the supracondylar region (n = 12). Demographic or outcome effects between fracture patterns were not found. On average of 4.2 years (2.0-10.4) after treatment, the mean reported Parker score was 5.5 (1-9). CONCLUSION: ORIF with a single lateral locking plate is safe for type Vancouver C fractures with a well-fixed hip stem. Therefore, we do not recommend routinely revision arthroplasty or orthogonal double plating. Three subtypes of fractures within Vancouver C demonstrated no significant differences in baseline data and outcome.


Assuntos
Artroplastia de Quadril , Fraturas do Fêmur , Fraturas Periprotéticas , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Estudos Retrospectivos , Consolidação da Fratura , Fraturas Periprotéticas/diagnóstico por imagem , Fraturas Periprotéticas/etiologia , Fraturas Periprotéticas/cirurgia , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/etiologia , Fraturas do Fêmur/cirurgia , Artroplastia de Quadril/efeitos adversos , Fixação Interna de Fraturas/efeitos adversos , Reoperação , Placas Ósseas , Resultado do Tratamento
7.
HNO ; 71(8): 513-520, 2023 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-37219567

RESUMO

Bimodal provision of patients with asymmetric hearing loss with a hearing aid ipsilaterally and a cochlear implant (CI) contralaterally is probably the most complicated type of CI provision due to a variety of inherent variables. This review article presents all the systematic interaural mismatches between electric and acoustic stimulation that can occur in bimodal listeners. One of these mismatches is the interaural latency offset, i.e., the time difference of activation of the auditory nerve by acoustic and electric stimulation. Methods for quantifying this offset are presented by registering electrically and acoustically evoked potentials and measuring processing delays in the devices. Technical compensation of the interaural latency offset and its positive effect on sound localization ability in bimodal listeners is also described. Finally, most recent findings are discussed which may explain why compensation of the interaural latency offset does not improve speech understanding in noise in bimodal listeners.


Assuntos
Implante Coclear , Implantes Cocleares , Auxiliares de Audição , Localização de Som , Percepção da Fala , Humanos , Localização de Som/fisiologia , Estimulação Acústica/métodos
8.
Int Orthop ; 46(5): 953-961, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35129644

RESUMO

PURPOSE: Two-stage exchange is the treatment of choice for periprosthetic joint infection (PJI). Factors and outcomes associated with infection recurrence for hip PJI are limited. The primary aim of this study was to determine factors associated with infection recurrence after two-stage exchange. Secondary aims were survival, mobility, and the EuroQol five-dimension scale (EQ-5D-5L) health state. METHODS: We retrospectively investigated patients with two-stage exchange for hip PJI at our institution from 2006 to 2017. Follow-up was conducted for a minimum of four years after the reimplantation. RESULTS: We included 135 patients with 139 hip PJIs. The mean age of the patients was 69.6 years (range 32-88). The infection recurrence rate was 14.4% (n = 20) after a mean follow-up of 8.0 years (range 4.0-13.1). Four factors for recurrence were identified at the time of the first stage: previous orthopaedic diagnoses (p < 0.001), type of explanted prosthesis (p = 0.004), cultured microorganisms (p = 0.033), and sinus tract (p = 0.035). A longer surgical reimplantation time (p = 0.015) was the only one factor found at the second stage. The estimated Kaplan-Meier survival for the total sample was 9.0 years (95% confidence interval 8.3-9.8), without significant difference for those with infection recurrence compared to recurrence-free patients (log-rank 0.931). At the time of follow-up, 89 patients were alive. For these patients, Parker mobility score (p = 0.102), EuroQol five-dimensional scale (p = 0.099), and EQ Visual Analogue Scale (EQ-VAS) (p = 0.027) were inferior in those with infection recurrence, but significance was found only for VAS. CONCLUSION: In this study with mid- to long-term follow-up, five factors for infection recurrence were identified. Recurrence did not affect survival, but health-related quality of life was inferior compared to recurrence-free patients. The results suggest that the period of the first stage including previous orthopaedic diagnoses requires more consideration in the future.


Assuntos
Artrite Infecciosa , Artroplastia de Quadril , Infecções Relacionadas à Prótese , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Artrite Infecciosa/cirurgia , Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/métodos , Humanos , Pessoa de Meia-Idade , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/cirurgia , Qualidade de Vida , Recidiva , Reoperação/métodos , Estudos Retrospectivos , Resultado do Tratamento
9.
Hum Mol Genet ; 28(4): 615-627, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30339187

RESUMO

Axonopathies are neurodegenerative disorders caused by axonal degeneration, affecting predominantly the longest neurons. Several of these axonopathies are caused by genetic defects in proteins involved in the shaping and dynamics of the endoplasmic reticulum (ER); however, it is unclear how these defects impinge on neuronal survival. Given its central and widespread position within a cell, the ER is a pivotal player in inter-organelle communication. Here, we demonstrate that defects in the ER fusion protein ATL3, which were identified in patients suffering from hereditary sensory and autonomic neuropathy, result in an increased number of ER-mitochondria contact sites both in HeLa cells and in patient-derived fibroblasts. This increased contact is reflected in higher phospholipid metabolism, upregulated autophagy and augmented Ca2+ crosstalk between both organelles. Moreover, the mitochondria in these cells display lowered motility, and the number of axonal mitochondria in neurons expressing disease-causing mutations in ATL3 is strongly decreased. These results underscore the functional interdependence of subcellular organelles in health and disease and show that disorders caused by ER-shaping defects are more complex than previously assumed.


Assuntos
Axônios/metabolismo , Retículo Endoplasmático/genética , GTP Fosfo-Hidrolases/genética , Neuropatias Hereditárias Sensoriais e Autônomas/genética , Autofagia/genética , Axônios/patologia , Cálcio/metabolismo , Sinalização do Cálcio/genética , Retículo Endoplasmático/metabolismo , Fibroblastos/metabolismo , Células HeLa , Neuropatias Hereditárias Sensoriais e Autônomas/metabolismo , Neuropatias Hereditárias Sensoriais e Autônomas/patologia , Humanos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mutação , Neurônios/metabolismo , Neurônios/patologia
10.
Am J Hum Genet ; 102(4): 557-573, 2018 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-29576218

RESUMO

Mitochondrial disorders causing neurodegeneration in childhood are genetically heterogeneous, and the underlying genetic etiology remains unknown in many affected individuals. We identified biallelic variants in PMPCB in individuals of four families including one family with two affected siblings with neurodegeneration and cerebellar atrophy. PMPCB encodes the catalytic subunit of the essential mitochondrial processing protease (MPP), which is required for maturation of the majority of mitochondrial precursor proteins. Mitochondria isolated from two fibroblast cell lines and induced pluripotent stem cells derived from one affected individual and differentiated neuroepithelial stem cells showed reduced PMPCB levels and accumulation of the processing intermediate of frataxin, a sensitive substrate for MPP dysfunction. Introduction of the identified PMPCB variants into the homologous S. cerevisiae Mas1 protein resulted in a severe growth and MPP processing defect leading to the accumulation of mitochondrial precursor proteins and early impairment of the biogenesis of iron-sulfur clusters, which are indispensable for a broad range of crucial cellular functions. Analysis of biopsy materials of an affected individual revealed changes and decreased activity in iron-sulfur cluster-containing respiratory chain complexes and dysfunction of mitochondrial and cytosolic Fe-S cluster-dependent enzymes. We conclude that biallelic mutations in PMPCB cause defects in MPP proteolytic activity leading to dysregulation of iron-sulfur cluster biogenesis and triggering a complex neurological phenotype of neurodegeneration in early childhood.


Assuntos
Domínio Catalítico/genética , Metaloendopeptidases/genética , Mutação/genética , Degeneração Neural/genética , Criança , Pré-Escolar , Derme/patologia , Transporte de Elétrons , Feminino , Fibroblastos/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Proteínas Ferro-Enxofre/genética , Imageamento por Ressonância Magnética , Masculino , Mitocôndrias/metabolismo , Linhagem , Proto-Oncogene Mas , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Peptidase de Processamento Mitocondrial
11.
Cell Biol Toxicol ; 37(2): 229-243, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32564278

RESUMO

The embryonic stem cell test (EST) represents the only validated and accepted in vitro system for the detection and classification of compounds according to their developmental and reproductive teratogenic potency. The widespread implementation of the EST, however, in particular for routine application in pharmaceutical development, has not been achieved so far. Several drawbacks still limit the high-throughput screening of potential drug candidates in this format: The long assay period, the use of non-homogeneous viability assays, the low throughput analysis of marker protein expression and the compatibility of the assay procedures to automation. We have therefore introduced several advancements into the EST workflow: A reduction of the assay period, an introduction of homogeneous viability assays, and a straightforward analysis of marker proteins by flow cytometry and high content imaging to assess the impact of small molecules on differentiation capacity. Most importantly, essential parts of the assay procedure have been adapted to lab automation in 96-well format, thus enabling the interrogation of several compounds in parallel. In addition, extensive investigations were performed to explore the predictive capacity of this next-generation EST, by testing a set of well-known embryotoxicants that encompasses the full range of chemical-inherent embryotoxic potencies possible. Due to these significant improvements, the augmented workflow provides a basis for a sensitive, more rapid, and reproducible high throughput screening compatible platform to predict in vivo developmental toxicity from in vitro data which paves the road towards application in an industrial setting. Graphical abstract •The embryonic stem cell test to predict teratogenicity was made automation-compatible. •Several key improvements to the assay procedure have been introduced to increase performance. •The workflow was adapted to human iPS cells and isogenic fibroblast donor cells.


Assuntos
Desenvolvimento Embrionário , Ensaios de Triagem em Larga Escala , Células-Tronco Pluripotentes/metabolismo , Reprodução , Bibliotecas de Moléculas Pequenas/farmacologia , Testes de Toxicidade , Trifosfato de Adenosina/farmacologia , Animais , Automação , Bioensaio , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Corpos Embrioides/efeitos dos fármacos , Corpos Embrioides/metabolismo , Desenvolvimento Embrionário/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Células-Tronco Pluripotentes Induzidas/metabolismo , Camundongos , Células-Tronco Embrionárias Murinas/efeitos dos fármacos , Células-Tronco Embrionárias Murinas/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Células NIH 3T3 , Células-Tronco Pluripotentes/efeitos dos fármacos , Reprodução/efeitos dos fármacos
12.
Nanotechnology ; 32(42)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34261048

RESUMO

The discovery of ferroelectricity in the fluorite structure based hafnium oxide (HfO2) material sparked major efforts for reviving the ferroelectric field effect transistor (FeFET) memory concept. A Novel metal-ferroelectric-metal-ferroelectric-insulator-semiconductor (MFMFIS) FeFET memory is reported based on dual ferroelectric integration as an MFM and MFIS in a single gate stack using Si-doped Hafnium oxide (HSO) ferroelectric (FE) material. The MFMFIS top and bottom electrode contacts, dual HSO based ferroelectric layers, and tailored MFM to MFIS area ratio (AR-TB) provide a flexible stack structure tuning for improving the FeFET performance. The AR-TB tuning shows a tradeoff between the MFM voltage increase and the weaker FET Si channel inversion, particularly notable in the drain saturation currentID(sat)when the AR-TB ratio decreases. Dual HSO ferroelectric layer integration enables a maximized memory window (MW) and dynamic control of its size by tuning the MFM to MFIS switching contribution through the AR-TB change. The stack structure control via the AR-TB tuning shows further merits in terms of a low voltage switching for a saturated MW size, an extremely linear at wide dynamic range of the current update, as well as high symmetry in the long term synaptic potentiation and depression. The MFMFIS stack reliability is reported in terms of the switching variability, temperature dependence, endurance, and retention. The MFMFIS concept is thoroughly discussed revealing profound insights on the optimal MFMFIS stack structure control for enhancing the FeFET memory performance.

13.
Unfallchirurg ; 124(11): 916-922, 2021 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-33416928

RESUMO

INTRODUCTION: Hip replacement for pertrochanteric femoral fractures (PF) is challenging due to its complexity. Studies regarding this procedures are limited, therefore this monocentric study was conducted. The null hypothesis was no effect between replacement and internal fixation according to revision and mortality. MATERIAL AND METHODS: Using an electronic database, patients who had received a hip replacement between 2007 and 2016 for a PF with a concomitant coxarthrosis were included in the study. The comparison group consisted of 1000 osteosyntheses for the treatment of PF. With the exception of coxarthrosis, the same inclusion and exclusion criteria were defined. Surgical revision and mortality with endpoint 2 years after the operation were the primary outcomes. At least 2 years postoperatively, a telephone follow-up was done with living patients who underwent replacement. RESULTS: Records of 90 hip replacements and 15 baseline characteristics were reviewed (e.g., age, sex, body mass index, preoperative blood values, ASA classification, dementia, fracture classification). Replacement was significantly associated with a delay to operation (p < 0.001), a longer duration of operation (p < 0.001), an increased blood loss (p < 0.001), more blood transfusions (p < 0.001), and a longer inpatient stay (p = 0.026). According to the primary outcome, the mortality rate (p = 0.002) and the rate of infection in a subgroup analysis (p = 0.031) were also significantly increased. Using Cox regression, replacement was associated with a significantly higher probability of a shorter survival rate (odds ratio: 1.438, confidence interval: 1.054-1.962). Therefore, the null hypothesis was rejected. At the follow-up 6.1 years postoperatively (3.2-8.6 years), only 17 patients with replacement (20%) were still alive. The mean Parker mobility score was 5.0 points (range 3-9 points). CONCLUSION: In this study, a significantly higher rate of infection and mortality was observed in patients with hip replacement for a PF and with a concomitant coxarthrosis; compared to osteosynthesis of PF without coxarthrosis. Further studies are mandatory to provide the appropriate treatment for patients with this fracture pattern.


Assuntos
Artroplastia de Quadril , Fraturas do Fêmur , Osteoartrite do Quadril , Grupos Controle , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/cirurgia , Fixação Interna de Fraturas , Humanos , Osteoartrite do Quadril/cirurgia , Reoperação , Estudos Retrospectivos
14.
Emerg Infect Dis ; 26(4): 821-823, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32187005

RESUMO

Infestation with Baylisascaris procyonis, a gastrointestinal nematode of the raccoon, can cause fatal disease in humans. We found that the parasite is widespread in central Germany and can pose a public health risk. The spread of B. procyonis roundworms into nematode-free raccoon populations needs to be monitored.


Assuntos
Infecções por Ascaridida , Ascaridoidea , Animais , Infecções por Ascaridida/epidemiologia , Infecções por Ascaridida/veterinária , Alemanha/epidemiologia , Luxemburgo , Guaxinins
15.
Bioinformatics ; 35(22): 4770-4772, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31192347

RESUMO

SUMMARY: Long-read third-generation nanopore sequencing enables researchers to now address a range of questions that are difficult to tackle with short read approaches. The rapidly expanding user base and continuously increasing throughput have sparked the development of a growing number of specialized analysis tools. However, streamlined processing of nanopore datasets using reproducible and transparent workflows is still lacking. Here we present Nanopype, a nanopore data processing pipeline that integrates a diverse set of established bioinformatics software while maintaining consistent and standardized output formats. Seamless integration into compute cluster environments makes the framework suitable for high-throughput applications. As a result, Nanopype facilitates comparability of nanopore data analysis workflows and thereby should enhance the reproducibility of biological insights. AVAILABILITY AND IMPLEMENTATION: https://github.com/giesselmann/nanopype, https://nanopype.readthedocs.io. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Nanoporos , Sequenciamento de Nucleotídeos em Larga Escala , Reprodutibilidade dos Testes , Software , Fluxo de Trabalho
16.
Stem Cells ; 37(11): 1429-1440, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31339593

RESUMO

During nervous system development, early neuroepithelial stem (NES) cells with a highly polarized morphology and responsiveness to regionalizing morphogens give rise to radial glia (RG) cells, which generate region-specific neurons. Recently, stable neural cell populations reminiscent of NES cells have been obtained from pluripotent stem cells and the fetal human hindbrain. Here, we explore whether these cell populations, similar to their in vivo counterparts, can give rise to neural stem (NS) cells with RG-like properties and whether region-specific NS cells can be generated from NES cells with different regional identities. In vivo RG cells are thought to form from NES cells with the onset of neurogenesis. Therefore, we cultured NES cells temporarily in differentiating conditions. Upon reinitiation of growth factor treatment, cells were found to enter a developmental stage reflecting major characteristics of RG-like NS cells. These NES cell-derived NS cells exhibited a very similar morphology and marker expression as primary NS cells generated from human fetal tissue, indicating that conversion of NES cells into NS cells recapitulates the developmental progression of early NES cells into RG cells observed in vivo. Importantly, NS cells generated from NES cells with different regional identities exhibited stable region-specific transcription factor expression and generated neurons appropriate for their positional identity. Stem Cells 2019;37:1429-1440.


Assuntos
Encéfalo/citologia , Encéfalo/metabolismo , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Células Ependimogliais/citologia , Células Ependimogliais/metabolismo , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Células Neuroepiteliais/citologia , Células Neuroepiteliais/metabolismo , Diferenciação Celular/fisiologia , Linhagem Celular , Células Cultivadas , Humanos , Neurônios/citologia , Neurônios/metabolismo , Rombencéfalo/citologia , Rombencéfalo/metabolismo
17.
Int Orthop ; 44(7): 1391-1399, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32296909

RESUMO

PURPOSE: The aim of this study was to assess patients treated for interprosthetic femoral fractures (IFFs). METHOD: Based on our database, we performed a retrospective single-center analysis of patients who underwent surgery for the treatment of IFFs. We evaluated patient demographics, fracture patterns, type of surgery, revision, and mortality for a minimum of one year after treatment. Outcomes were assessed via telephone using the Parker score. RESULTS: Fifty consecutive patients were enrolled. An analysis of fracture patterns revealed three different types: proximal (n = 19), intermediate (n = 13), and distal (n = 18). Treatment included internal fixation for stable components and revision arthroplasty for loose implants; and a lateral locking plate was the most commonly applied device. The mean follow-up time of the total sample was 5.7 years after the operation. The total revision rate was 22%, and the highest revision rate was documented for revision arthroplasty. The one year mortality rate for the sample was 14%, and fracture patterns and treatment revealed no effects on mortality. Living patients (n = 23) were followed up for an average of 4.9 years after treatment. Only six patients reported the best Parker score (mean, 5.0; range 0-9). CONCLUSION: IFFs can be divided into three groups irrespective of the type of stem or bone quality, but fixation (stable or loose) must also be considered to determine the treatment. Fracture patterns and treatment revealed no effects on mortality. There are many treatment options but no single solution for IFFs.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Fraturas do Fêmur , Fraturas Periprotéticas , Artroplastia de Quadril/efeitos adversos , Placas Ósseas , Fraturas do Fêmur/cirurgia , Fixação Interna de Fraturas/efeitos adversos , Humanos , Fraturas Periprotéticas/epidemiologia , Fraturas Periprotéticas/cirurgia , Reoperação , Estudos Retrospectivos , Resultado do Tratamento
18.
Unfallchirurg ; 123(4): 326-329, 2020 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-32052083

RESUMO

According to the manufacturer's instructions the application of a PHILOS plate is restricted to humeral fractures. An extension to other anatomical regions of the body is not provided; however, based on the anatomical design of the plate it was observed that the application of this plate also appears to be possible for the distal tibia. This article reports three different osteosyntheses by a reverse PHILOS plate on the medial malleolus and on the distal tibia posteriorly with a short and a long PHILOS plate design. In summary, the applications have so far resulted in primary wound healing with correct consolidation of the fractures.


Assuntos
Placas Ósseas , Fraturas do Úmero , Fraturas da Tíbia , Fixação Interna de Fraturas , Humanos , Fraturas do Úmero/cirurgia , Ossos do Tarso/lesões , Ossos do Tarso/cirurgia , Tíbia , Fraturas da Tíbia/cirurgia
19.
Eur J Orthop Surg Traumatol ; 30(6): 1083-1088, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32342194

RESUMO

PURPOSE: The aim of this study was to assess patients with Parkinson's disease (PD) in comparison with patients without PD for the treatment of hip fractures. Therefore, we performed a mono-centre study including 145 patients with PD and 2135 consecutive patients without PD as a concurrent group (C). METHODS: For analysis, we used our database, in which any type of hip fracture was enrolled. The study period ranged from 2007 to 2017, and the patient age was ≥ 60 years. Overall, 10 variables were included. The primary measures were operations for any reason, infection, dislocation, failure, and mortality. The secondary outcome was any de novo fracture based on a new fall. The follow-up period for every living patient was 2 years after the operation. Any missing data were retrospectively evaluated via telephone. The hypothesis was no effect between the two groups. RESULTS: No significant differences were observed regarding revision (p = 0.348), infection (p = 0.207), dislocation (p = 0.785), failure of internal fixation (p = 0.368), failure of replacement (p = 0.174), and de novo fractures (p = 0.287). However, patients with PD sustained a contralateral hip fracture significantly more often (p < 0.001). Kaplan-Meier survival analysis demonstrated no effects up to 2 years after the operation (log rank 0.259). CONCLUSION: Compared to a concurrent group, patients with PD demonstrated no more complications and similar mortality rates within 2 years after surgery. The rate of dislocation after hip replacement was also not increased. A contralateral hip fracture was the most common de novo fracture in PD. Further studies should investigate measures reducing the risk for any new falls in PD.


Assuntos
Acidentes por Quedas , Fixação de Fratura , Fraturas do Quadril , Doença de Parkinson , Complicações Pós-Operatórias , Reoperação/estatística & dados numéricos , Acidentes por Quedas/prevenção & controle , Acidentes por Quedas/estatística & dados numéricos , Idoso de 80 Anos ou mais , Feminino , Fixação de Fratura/efeitos adversos , Fixação de Fratura/métodos , Fixação de Fratura/estatística & dados numéricos , Alemanha/epidemiologia , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/etiologia , Fraturas do Quadril/cirurgia , Humanos , Estimativa de Kaplan-Meier , Masculino , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico , Doença de Parkinson/epidemiologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Fatores de Risco
20.
Arch Virol ; 163(11): 3131-3134, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30062638

RESUMO

European populations of free-living wildcats have been shown to be exposed to cat viruses. Luxembourg has a high degree of habitat fragmentation, and hybridisation rates between domestic cats and wildcats are high. We therefore assessed the seroprevalence of six viruses in 34 serum samples collected between 2001 and 2016 from wildcats in Luxembourg. The values for feline leukemia virus (FeLV; 52.9%) and feline coronavirus (FCoV; 47.1%) were amongst the highest reported for wildcats. We found evidence for the cumulative likelihood of exposure to FCoV affecting its seroprevalence. Routine monitoring of viral agents in this strictly protected species should be considered.


Assuntos
Anticorpos Antivirais/sangue , Doenças do Gato/virologia , Viroses/veterinária , Vírus/isolamento & purificação , Animais , Animais Selvagens/sangue , Animais Selvagens/virologia , Doenças do Gato/sangue , Doenças do Gato/epidemiologia , Gatos , Luxemburgo/epidemiologia , Filogenia , Estudos Soroepidemiológicos , Viroses/sangue , Viroses/epidemiologia , Viroses/virologia , Vírus/classificação , Vírus/genética , Vírus/imunologia
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