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1.
Sci Adv ; 10(23): eadk8471, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38838137

RESUMO

Deep random forest (DRF), which combines deep learning and random forest, exhibits comparable accuracy, interpretability, low memory and computational overhead to deep neural networks (DNNs) in edge intelligence tasks. However, efficient DRF accelerator is lagging behind its DNN counterparts. The key to DRF acceleration lies in realizing the branch-split operation at decision nodes. In this work, we propose implementing DRF through associative searches realized with ferroelectric analog content addressable memory (ACAM). Utilizing only two ferroelectric field effect transistors (FeFETs), the ultra-compact ACAM cell performs energy-efficient branch-split operations by storing decision boundaries as analog polarization states in FeFETs. The DRF accelerator architecture and its model mapping to ACAM arrays are presented. The functionality, characteristics, and scalability of the FeFET ACAM DRF and its robustness against FeFET device non-idealities are validated in experiments and simulations. Evaluations show that the FeFET ACAM DRF accelerator achieves ∼106×/10× and ∼106×/2.5× improvements in energy and latency, respectively, compared to other DRF hardware implementations on state-of-the-art CPU/ReRAM.

2.
Surg Neurol Int ; 15: 139, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38741994

RESUMO

Background: Sciatica is typically caused by disc herniations or spinal stenosis. Extraspinal compression of the sciatic nerve is less frequent. Case Description: We report a rare case of sciatica with compression of the sciatic nerve by a low-flow vascular malformation in a 24-year-old female patient. The special feature of this case was sciatica along the S1 dermatome, which only occurred in the sitting position and inclination because of compression of the sciatic nerve between the vascular malformation and the lesser trochanter. Spinal imaging showed no abnormal findings. Surgery was performed interdisciplinary and included neurosurgery, vascular surgery, and trauma surgery. After surgery, the patient became symptom-free. Conclusion: Rare and extraspinal causes of local compression of the sciatic nerve should be considered, especially in cases of lacking spinal imaging correlation and untypical clinical presentation. Interdisciplinary surgical cooperation is of special value in cases of rare entities and uncommon locations.

3.
Z Orthop Unfall ; 2024 Apr 15.
Artigo em Inglês, Alemão | MEDLINE | ID: mdl-38621696

RESUMO

Prozessänderungen im perioperativen Setting werden selten analysiert, weil ihre Ergebnisse nicht unmittelbar fassbar sind und es einer hohen Fallzahl bedarf. Primäres Ziel war es, Prozessänderungen retrospektiv anhand proximaler Femurfrakturen (PF) zu evaluieren und deren Effekt mit verschiedenen Zielkriterien zu überprüfen. Sekundäres Ziel war die Definition möglicher Qualitätskriterien für die Versorgung von PF.Retrospektive Analyse der Datenbank eines Level-1-Traumazentrums zu PF. Eingeschlossen wurden alle osteosynthetisch und endoprothetisch versorgten PF im Behandlungszeitraum vom 01.01.2006 bis 31.12.2021. Der Zeitraum von 16 Jahren wurde für die Statistik trichotom aufgeteilt und die ersten 6 Jahre als Ausgangsbasis verwendet. Insgesamt 10 Prozessänderungen wurden in den folgenden 10 Jahren vorgenommen. Die Auswirkungen dieser Änderungen wurden anhand 1. der operativen Revisionsrate, 2. der Infektionsrate, 3. der perioperativen Transfusionsrate sowie 4. der 1-Jahres-Letalität überprüft.Insgesamt 4163 PF wurden analysiert. Hinsichtlich der Zielkriterien zeigten die Änderungen der ersten 5 Jahre (2012-2016; intramedulläres Verfahren für Osteosynthesen sowie Einwegabdeckung und Einwegkittel) den stärksten Effekt mit einer erstmaligen Senkung der operativen Revisionsrate unter 10% auf Dauer. Weitere Prozessoptimierungen der letzten 5 Jahre (2017-2021) erbrachten ebenfalls messbare Verbesserungen (Senkung der Infektions- und Transfusionsrate). Die 1-Jahres-Letalität blieb unverändert, auch während der COVID-19-Pandemie.Prozessänderungen bei PF führen nicht unmittelbar zu objektiv messbaren Verbesserungen. Rückblickend erscheint der Paradigmenwechsel von extra- auf intramedulläre Osteosynthese den höchsten Effekt erzielt zu haben, wenngleich über die letzten 10 Jahre eine schrittweise Besserung aller Zielkriterien eintrat - mit Ausnahme der Letalität. Als objektive Qualitätskontrolle sollte eine 1-Jahres-Revisionsrate unter 10% angestrebt sein.

4.
Trials ; 25(1): 247, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594753

RESUMO

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is essential for antidepressant treatment of major depressive disorder (MDD). Our repeated studies suggest that DNA methylation of a specific CpG site in the promoter region of exon IV of the BDNF gene (CpG -87) might be predictive of the efficacy of monoaminergic antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and others. This trial aims to evaluate whether knowing the biomarker is non-inferior to treatment-as-usual (TAU) regarding remission rates while exhibiting significantly fewer adverse events (AE). METHODS: The BDNF trial is a prospective, randomized, rater-blinded diagnostic study conducted at five university hospitals in Germany. The study's main hypothesis is that {1} knowing the methylation status of CpG -87 is non-inferior to not knowing it with respect to the remission rate while it significantly reduces the AE rate in patients experiencing at least one AE. The baseline assessment will occur upon hospitalization and a follow-up assessment on day 49 (± 3). A telephone follow-up will be conducted on day 70 (± 3). A total of 256 patients will be recruited, and methylation will be evaluated in all participants. They will be randomly assigned to either the marker or the TAU group. In the marker group, the methylation results will be shared with both the patient and their treating physician. In the TAU group, neither the patients nor their treating physicians will receive the marker status. The primary endpoints include the rate of patients achieving remission on day 49 (± 3), defined as a score of ≤ 10 on the Hamilton Depression Rating Scale (HDRS-24), and the occurrence of AE. ETHICS AND DISSEMINATION: The trial protocol has received approval from the Institutional Review Boards at the five participating universities. This trial holds significance in generating valuable data on a predictive biomarker for antidepressant treatment in patients with MDD. The findings will be shared with study participants, disseminated through professional society meetings, and published in peer-reviewed journals. TRIAL REGISTRATION: German Clinical Trial Register DRKS00032503. Registered on 17 August 2023.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Transtorno Depressivo Maior , Humanos , Fator Neurotrófico Derivado do Encéfalo/genética , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/genética , Estudos Prospectivos , Antidepressivos/efeitos adversos , Inibidores Seletivos de Recaptação de Serotonina , Metilação , Biomarcadores
6.
Nat Commun ; 15(1): 2419, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38499524

RESUMO

Computationally hard combinatorial optimization problems (COPs) are ubiquitous in many applications. Various digital annealers, dynamical Ising machines, and quantum/photonic systems have been developed for solving COPs, but they still suffer from the memory access issue, scalability, restricted applicability to certain types of COPs, and VLSI-incompatibility, respectively. Here we report a ferroelectric field effect transistor (FeFET) based compute-in-memory (CiM) annealer for solving larger-scale COPs efficiently. Our CiM annealer converts COPs into quadratic unconstrained binary optimization (QUBO) formulations, and uniquely accelerates in-situ the core vector-matrix-vector (VMV) multiplication operations of QUBO formulations in a single step. Specifically, the three-terminal FeFET structure allows for lossless compression of the stored QUBO matrix, achieving a remarkably 75% chip size saving when solving Max-Cut problems. A multi-epoch simulated annealing (MESA) algorithm is proposed for efficient annealing, achieving up to 27% better solution and ~ 2X speedup than conventional simulated annealing. Experimental validation is performed using the first integrated FeFET chip on 28nm HKMG CMOS technology, indicating great promise of FeFET CiM array in solving general COPs.

8.
Artigo em Inglês | MEDLINE | ID: mdl-38530409

RESUMO

PURPOSE: The incidence of peri-implant femoral fractures (PIFF) is increasing. Information regarding outcomes, timing of surgery, risk factors, and a clinically applicable treatment algorithm are lacking. The aim of this study was to identify outcome-related risk factors and to derive a treatment algorithm. METHODS: Sixty-four PIFFs treated between 01.01.2006 and 31.12.2020 in a level I trauma centre were evaluated retrospectively for fracture pattern, surgical technique, risk factors, complications, and 1-year mortality. The study was approved by the ethics committee (No. 21-2714-104). RESULTS: One-year mortality was 24.1%. Surgical complications occurred in 4.7%, and general complications in 15.6% of the patients. General complications, low haemoglobin level at admission, elevated CHA2DS2-VASc, and Charlson score resulted in increased 1-year mortality. Time to surgery > 24 h did not increase complication or mortality rates. The three predominant fracture patterns were fractures close or distal to cephalomedullary nails, close or proximal to distal lateral plates, and close or distal to sliding hip screws. Recommendations for surgical treatment were derived: Osteosynthesis should enable as much weight-bearing as possible; the initial implant should only be removed, if this is essential for the new osteosynthesis; lateral locking plates should span the whole femur; antegrade nails should have a cephalomedullary component to avoid consecutive femoral neck fractures; implants should overlap to reduce the risk of consecutive inter-implant fractures. CONCLUSION: Risk factors for 1-year mortality in patients with PIFFs were identified. A treatment algorithm and general principles for surgery of PIFFs were developed.

9.
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.

10.
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
11.
Unfallchirurgie (Heidelb) ; 127(5): 381-390, 2024 May.
Artigo em Alemão | MEDLINE | ID: mdl-38443720

RESUMO

BACKGROUND: Fractures of the navicular bone are rare and the number of those treated surgically is even smaller. Moreover, scientific analyses on this topic are only sporadically present in the literature, therefore this retrospective and monocentric study was initiated. METHODS: A total of 30 patients with 30 fractures were included. With the exception of one primary fusion, all patients underwent open reduction with internal osteosynthesis. Clinical and radiological follow-up was performed at least 2 years postoperatively using AOFAS-Score, SF-12 and a radiological examination. The primary objectives were the clinical and radiologic outcomes as mid-term to long-term outcomes. The secondary objective was to compare these results with two existing computed tomography (CT) fracture classifications in terms of their association with the outcome. RESULTS: The median follow-up was 7.8 years (range 2-16.2 years) postoperatively. One patient suffered an infection, four patients required secondary arthrodesis and eight patients had to change their occupation. The mean AOFAS-Score was 80.8/100 and the mean physical and mental SF-12 component summary scores were 47.1 and 55.7 points, respectively. Male sex and arthrodesis were associated with worse outcomes in both scores but not patient age or ipsilateral concomitant injuries. Both CT fracture classifications showed low predictive value. CONCLUSION: The severity of the injury in the preoperative CT showed no connection with the clinical outcome in the AOFAS-Score and SF-12 scores. Posttraumatic osteoarthritis and secondary arthrodesis are associated with a poor outcome. In the course of the observational period the reduction results improved, which was accompanied by a better clinical outcome.


Assuntos
Fixação Interna de Fraturas , Fraturas Ósseas , Ossos do Tarso , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Fixação Interna de Fraturas/efeitos adversos , Resultado do Tratamento , Ossos do Tarso/lesões , Ossos do Tarso/cirurgia , Ossos do Tarso/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/classificação , Idoso , Tomografia Computadorizada por Raios X , Adulto Jovem , Adolescente , Seguimentos
12.
Pathogens ; 13(2)2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38392891

RESUMO

Toxoplasma gondii is an obligate intracellular protozoan that causes toxoplasmosis in warm-blooded animals. Although most infections in humans and animals are subclinical, an infection can nevertheless be fatal. One of the important characteristics in the epidemiology of this parasite is waterborne transmission. The American mink (Neogale vison), a mammal closely adapted to freshwater ecosystems, is a potential sentinel for T. gondii. We analysed meat juice from the heart of 194 wild minks collected between 2019 and 2022 in five study areas from Germany and Poland and tested for the presence of antibodies against T. gondii. The analysis was performed using a commercial enzyme-linked immunosorbent assay test (ELISA). Antibodies were detected in 45.36% (88/194, 95% confidence interval (CI): 38.39-52.41%) of the analysed animals. While the prevalence values ranged from 37.50% to 49.30%, there was no significant difference in seroprevalence between the study areas. Juveniles were less likely to carry T. gondii antibodies than adults (odds ratio: 0.216), whereas there was no significant difference in prevalence between the sexes (odds ratio: 0.933). The results of our study show that contact with T. gondii is widespread in minks, and the parasite is common in inland freshwater ecosystems in Germany and Poland. This indicates that watercourses play an important role in the spread of T. gondii oocysts.

13.
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
14.
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
15.
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
16.
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
17.
Nat Commun ; 14(1): 8287, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38092753

RESUMO

Non-volatile memories (NVMs) have the potential to reshape next-generation memory systems because of their promising properties of near-zero leakage power consumption, high density and non-volatility. However, NVMs also face critical security threats that exploit the non-volatile property. Compared to volatile memory, the capability of retaining data even after power down makes NVM more vulnerable. Existing solutions to address the security issues of NVMs are mainly based on Advanced Encryption Standard (AES), which incurs significant performance and power overhead. In this paper, we propose a lightweight memory encryption/decryption scheme by exploiting in-situ memory operations with negligible overhead. To validate the feasibility of the encryption/decryption scheme, device-level and array-level experiments are performed using ferroelectric field effect transistor (FeFET) as an example NVM without loss of generality. Besides, a comprehensive evaluation is performed on a 128 × 128 FeFET AND-type memory array in terms of area, latency, power and throughput. Compared with the AES-based scheme, our scheme shows ~22.6×/~14.1× increase in encryption/decryption throughput with negligible power penalty. Furthermore, we evaluate the performance of our scheme over the AES-based scheme when deploying different neural network workloads. Our scheme yields significant latency reduction by 90% on average for encryption and decryption processes.

18.
BMC Med Genomics ; 16(1): 257, 2023 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-37872581

RESUMO

BACKGROUND: Bisulfite sequencing has long been considered the gold standard for measuring DNA methylation at single CpG resolution. However, in recent years several new approaches like nanopore sequencing have been developed due to hints for a partial error-proneness of bisulfite sequencing. Since these errors were shown to be sequence-specific, we aimed to verify the methylation data of a particular region of the TRPA1 promoter from our previous studies obtained by bisulfite sequencing. METHODS: We compared methylation rates determined by direct bisulfite sequencing and nanopore sequencing following Cas9-mediated PCR-free enrichment. RESULTS: We could show that CpG methylation levels above 20% corroborate well with our previous data. Within the range between 0 and 20% methylation, however, Sanger sequencing data have to be interpreted cautiously, at least in the investigated region of interest (TRPA1 promotor region). CONCLUSION: Based on the investigation of the TRPA1- region as an example, the present work can help in choosing the right method out of the two current main approaches for methylation analysis for different individual settings regarding many factors like cohort size, costs and prerequisites that should be fulfilled for each method. All in all, both methods have their raison d'être. Furthermore, the present paper contains and illustrates some important basic information and explanation of how guide RNAs should be located for an optimal outcome in Cas9 mediated PCR free target enrichment.


Assuntos
Sequenciamento por Nanoporos , Humanos , Ilhas de CpG , Metilação de DNA , Regiões Promotoras Genéticas , Análise de Sequência de DNA/métodos , Sulfitos , Canal de Cátion TRPA1/genética
19.
Nat Commun ; 14(1): 6348, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37816751

RESUMO

Advancements in AI led to the emergence of in-memory-computing architectures as a promising solution for the associated computing and memory challenges. This study introduces a novel in-memory-computing (IMC) crossbar macro utilizing a multi-level ferroelectric field-effect transistor (FeFET) cell for multi-bit multiply and accumulate (MAC) operations. The proposed 1FeFET-1R cell design stores multi-bit information while minimizing device variability effects on accuracy. Experimental validation was performed using 28 nm HKMG technology-based FeFET devices. Unlike traditional resistive memory-based analog computing, our approach leverages the electrical characteristics of stored data within the memory cell to derive MAC operation results encoded in activation time and accumulated current. Remarkably, our design achieves 96.6% accuracy for handwriting recognition and 91.5% accuracy for image classification without extra training. Furthermore, it demonstrates exceptional performance, achieving 885.4 TOPS/W-nearly double that of existing designs. This study represents the first successful implementation of an in-memory macro using a multi-state FeFET cell for complete MAC operations, preserving crossbar density without additional structural overhead.

20.
Orthopadie (Heidelb) ; 52(11): 916-923, 2023 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-37555977

RESUMO

BACKGROUND: Interprosthetic femur fractures (IFF) are rare injuries, whose surgical treatment is basically with osteosynthesis or revision arthroplasty. Various therapy algorithms have been proposed based on very small study collectives. Factors influencing the outcome are not known. OBJECTIVES: The aim of the retrospective monocentric study is to derive a treatment algorithm based on a large number of cases and to identify factors influencing the outcome. MATERIALS AND METHODS: Between 2006 and 2020, 70 IFF were identified. The surgical treatment comprised 38 osteosyntheses, 30 revision arthroplasties and 2 amputations. With classification and time to surgery, 69 perioperative variables were recorded. General and operative complications, as well as mortality, were determined in the follow-up period of 1 year. RESULTS: ASA and Charlson score correlated with 1­year-mortality. In addition, preoperatively increased CRP levels, reduced hemoglobin and the CHA2DS2-VASc score were identified as factors influencing mortality. Surgery within 24 h showed a trend towards fewer general complications. Transferred patients indicated an increased mortality. Based on classification according to Pires et al. or Füchtmeier et al. no clear treatment decision could be made. Relevant criteria for the surgical treatment were fracture localization, implant stability, bone vitality, anchoring possibility of the revision stem, as well as general condition of the patient. CONCLUSIONS: The identified factors influencing the outcome correspond to those of patients with hip fractures. IFF should be treated timely. A treatment path was developed on the basis of the largest patient group to date.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Fraturas do Fêmur , Fraturas Periprotéticas , Humanos , Estudos Retrospectivos , Fraturas Periprotéticas/cirurgia , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Reoperação/efeitos adversos , Fraturas do Fêmur/cirurgia , Fêmur/cirurgia
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