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1.
Artigo em Inglês | MEDLINE | ID: mdl-38963017

RESUMO

OBJECTIVES: To compare early implant placement (EP) to alveolar ridge preservation and delayed implant placement (ARP/DP) in terms of contour changes, along with clinician- and patient-reported outcome measures (PROMs) until the delivery of the implant-supported restoration. MATERIALS AND METHODS: Patients with a failing single tooth in the maxilla or mandible were recruited in two centres. After tooth extraction, patients were randomly assigned (1:1) to either EP or ARP/DP. At abutment connection and crown delivery, the buccal contour changes at 3 mm below the mucosal margin (primary outcome) along with clinician- (ease of treatment) and patient-reported outcomes were assessed using numeric rating scales and OHIP-14. RESULTS: A total of 46 patients were analysed. The mean buccal contour at abutment connection decreased by -1.2 ± 0.6 mm in group EP and -1.6 ± 0.8 mm in group ARP/DP (estimated mean difference; 0.45 [95%CI, -0.02; 0.94]; p = .061) with no significant differences between the groups. ARP/DP was consistently easier than EP across all stages of the surgery (estimated mean difference; 2.0 [95%CI, 1.3; 2.7] p < .001): during flap elevation (EP: 4.8 vs. ARP/DP: 1.6), implant placement (EP: 5.7 vs. ARP/DP: 2.2) and wound closure (EP: 3.4 vs. ARP/DP: 1.6). Both interventions improved quality of life but patients who underwent ARP/DP were significantly more satisfied at the time of crown delivery (ARP/DP: 9.6 vs. EP: 9.1, p = .02). CONCLUSIONS: EP and ARP/DP show no significant differences in buccal contour changes, aesthetics and patient-reported outcomes. However, ARP/DP is an easier procedure at all stages of the surgery compared to EP and could therefore be the preferred therapy for less experienced clinicians.

2.
JAC Antimicrob Resist ; 6(3): dlae085, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38847007

RESUMO

Objectives: Environmental conditions can influence mutation rates in bacteria. Fever is a common response to infection that alters the growth conditions of infecting bacteria. Here we examine how a temperature change, such as is associated with fever, affects the mutation rate towards antibiotic resistance. Methods: We used a fluctuation test to assess the mutation rate towards antibiotic resistance in Escherichia coli at two different temperatures: 37°C (normal temperature) and 40°C (fever temperature). We performed this measurement for three different antibiotics with different modes of action: ciprofloxacin, rifampicin and ampicillin. Results: In all cases, the mutation rate towards antibiotic resistance turned out to be temperature dependent, but in different ways. Fever temperatures led to a reduced mutation rate towards ampicillin resistance and an elevated mutation rate towards ciprofloxacin and rifampicin resistance. Conclusions: This study shows that the mutation rate towards antibiotic resistance is impacted by a small change in temperature, such as associated with fever. This opens a new avenue to mitigate the emergence of antibiotic resistance by coordinating the choice of an antibiotic with the decision of whether or not to suppress fever when treating a patient. Hence, optimized combinations of antibiotics and fever suppression strategies may be a new weapon in the battle against antibiotic resistance.

3.
J Environ Manage ; 365: 121554, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38905791

RESUMO

Vertebrate scavengers provide essential ecosystem services such as accelerating carrion decomposition by consuming carcasses, exposing tissues to microbial and invertebrate decomposers, and recycling nutrients back into the ecosystem. Some scavengers do not consume carcasses on site but rather scatter their remains in the surroundings, which might have important implications for nutrient transport, forensic investigations and the spread of diseases such as African Swine Fever. However, only a few studies have investigated and measured the scatter distances. Using wild boar (Sus scrofa) carcasses and limbs, we monitored scavenging behavior and measured scatter distances of mammals. We placed 20 carcasses (up to 25 kg) and 21 separate limbs equipped with very high frequency (VHF) transmitters and monitored scavenger activity using camera traps in a mountainous region in southeast Germany. Except for one carcass, all other carcasses and limbs were scattered. We measured 72 scatter distances (of 89 scattering events; mean = 232 m, maximum = 1250 m), of which 75% were dispersed up to 407 m. Scavengers moved scattered pieces into denser vegetation compared to the half-open vegetation at provisioning sites. Red foxes (Vulpes vulpes) were the most common scavenger species, contributing to 72 scattering events (58 measured scatter distances). Our results provide evidence of scatter distances farther than previously assumed and have far-reaching implications for disease management or forensic investigations, as the broader surroundings of carcasses must be included in search efforts to remove infectious material or relevant body parts for forensic analysis.

4.
BMC Res Notes ; 17(1): 175, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38915023

RESUMO

OBJECTIVE: New characterized carbohydrate-active enzymes are needed for use as tools to discriminate complex carbohydrate structural features. Fungal glycoside hydrolase family 3 (GH3) ß-xylosidases have been shown to be useful for the structural elucidation of glucuronic acid (GlcA) and arabinofuranose (Araf) substituted oligoxylosides. A homolog of these GH3 fungal enzymes from the bacterium Segatella baroniae (basonym Prevotella bryantii), Xyl3C, has been previously characterized, but those studies did not address important functional specificity features. In an interest to utilize this enzyme for laboratory methods intended to discriminate the structure of the non-reducing terminus of substituted xylooligosaccharides, we have further characterized this GH3 xylosidase. RESULTS: In addition to verification of basic functional characteristics of this xylosidase we have determined its mode of action as it relates to non-reducing end xylose release from GlcA and Araf substituted oligoxylosides. Xyl3C cleaves xylose from the non-reducing terminus of ß-1,4-xylan until occurrence of a penultimate substituted xylose. If this substitution is O2 linked, then Xyl3C removes the non-reducing xylose to leave the substituted xylose as the new non-reducing terminus. However, if the substitution is O3 linked, Xyl3C does not hydrolyze, thus leaving the substitution one-xylose (penultimate) from the non-reducing terminus. Hence, Xyl3C enables discrimination between O2 and O3 linked substitutions on the xylose penultimate to the non-reducing end. These findings are contrasted using a homologous enzyme also from S. baroniae, Xyl3B, which is found to yield a penultimate substituted nonreducing terminus regardless of which GlcA or Araf substitution exists.


Assuntos
Xilanos , Xilose , Xilosidases , Xilosidases/metabolismo , Xilosidases/genética , Xilosidases/química , Xilanos/metabolismo , Xilose/metabolismo , Especificidade por Substrato , Prevotella/enzimologia , Prevotella/genética , Oligossacarídeos/metabolismo , Oligossacarídeos/química , Glucuronatos/metabolismo , Arabinose/análogos & derivados
5.
Pers Soc Psychol Bull ; : 1461672241257139, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38859695

RESUMO

In Western societies, singlehood has become increasingly normative over historical time. But whether singles are more satisfied nowadays remains unclear. In this preregistered cohort-sequential study, we analyzed data from 2,936 German participants (M = 21.01 years, SD = 7.60 years) from different birth cohorts. Singlehood satisfaction and life satisfaction were reported annually at two different time periods (2008-2011 and 2018-2021). This design allowed us to compare earlier-born and later-born singles during adolescence (14-20 years), emerging adulthood (24-30 years), and established adulthood (34-40 years). Results from multilevel growth-curve models indicated that adolescent singles born in 2001 to 2003 (vs. 1991-1993) were more often single and more satisfied with singlehood. No cohort-related differences emerged among emerging and established adults. Younger age and lower neuroticism predicted higher satisfaction, regardless of birth cohort. The results highlight the importance of considering both societal and individual factors to understand singles' satisfaction.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38838049

RESUMO

OBJECTIVE: To determine whether combining cross-linked (CL) collagen-integrated xenogeneic bone blocks stabilized with the fixation of resorbable collagen membranes (CM) can enhance guided bone regeneration (GBR) in the overaugmented calvarial defect model. MATERIALS AND METHODS: Four circular defects with a diameter of 8 mm were prepared in the calvarium of 13 rabbits. Defects were randomly assigned to receive one of the following treatments: (i) non-cross-linked (NCL) porcine-derived collagen-embedded bone block covered by a CM without fixation (NCL + unfix group); (ii) NCL bone block covered by CM with fixation using bone-tack (NCL + fix group); (iii) cross-linked (CL) porcine-derived collagen-embedded bone block covered by CM without fixation (CL + unfix group); and (iv) CL bone block covered by CM with fixation using bone-tack fixation (CL + fix group). The efficacy of GBR was assessed through histological and molecular analyses after 2 and 8 weeks. RESULTS: At 2 weeks, there were no significant differences in histologically measured areas of newly formed bone among the groups. At 8 weeks, however, the CL + fix group exhibited a larger area of new bone (5.08 ± 1.09 mm2, mean ± standard deviation) compared to the NCL + unfix (1.62 ± 0.42 mm2; p < .0083), NCL + fix (3.97 ± 1.39 mm2) and CL + unfix (2.55 ± 1.04 mm2) groups. Additionally, the expression levels of tumour necrosis factor-alpha, fibroblast growth factor-2, vascular endothelial growth factor, osteocalcin and calcitonin receptor were significantly higher in the CL + fix group compared to the other three groups (p < .0083). CONCLUSION: Cross-linked bone blocks stabilized with collagen membrane fixation can significantly enhance GBR.

7.
EBioMedicine ; 104: 105167, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38805852

RESUMO

BACKGROUND: Tumour-infiltrating lymphocytes (TILs) are crucial for effective immune checkpoint blockade (ICB) therapy in solid tumours. However, ∼70% of these tumours exhibit poor lymphocyte infiltration, rendering ICB therapies less effective. METHODS: We developed a bioinformatics pipeline integrating multiple previously unconsidered factors or datasets, including tumour cell immune-related pathways, copy number variation (CNV), and single tumour cell sequencing data, as well as tumour mRNA-seq data and patient survival data, to identify targets that can potentially improve T cell infiltration and enhance ICB efficacy. Furthermore, we conducted wet-lab experiments and successfully validated one of the top-identified genes. FINDINGS: We applied this pipeline in solid tumours of the Cancer Genome Atlas (TCGA) and identified a set of genes in 18 cancer types that might potentially improve lymphocyte infiltration and ICB efficacy, providing a valuable drug target resource to be further explored. Importantly, we experimentally validated SUN1, which had not been linked to T cell infiltration and ICB therapy previously, but was one of the top-identified gene targets among 3 cancer types based on the pipeline, in a mouse colon cancer syngeneic model. We showed that Sun1 KO could significantly enhance antigen presentation, increase T-cell infiltration, and improve anti-PD1 treatment efficacy. Moreover, with a single-cell multiome analysis, we identified subgene regulatory networks (sub-GRNs) showing Stat proteins play important roles in enhancing the immune-related pathways in Sun1-KO cancer cells. INTERPRETATION: This study not only established a computational pipeline for discovering new gene targets and signalling pathways in cancer cells that block T-cell infiltration, but also provided a gene target pool for further exploration in improving lymphocyte infiltration and ICB efficacy in solid tumours. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.


Assuntos
Biologia Computacional , Inibidores de Checkpoint Imunológico , Linfócitos do Interstício Tumoral , Neoplasias , Transdução de Sinais , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Humanos , Biologia Computacional/métodos , Animais , Camundongos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica , Modelos Animais de Doenças
8.
Microorganisms ; 12(5)2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38792848

RESUMO

The aim of this study was to test the inactivation of viruses on germ carriers of different types of wood using a disinfectant in order to assess the biosafety of wood as a building material in animal husbandry. The laboratory disinfectant efficacy tests were based on German testing guidelines and current European standards. Five different types of wood germ carriers, i.e., spruce (Picea abies), pine (Pinus sylvestris), poplar (Populus sp.), beech (Fagus sylvatica) and Douglas fir (Pseudotsuga menziesii), were inoculated with enveloped or non-enveloped viruses and then treated with one of three different disinfectants. The results revealed that intact, fine-sawn timber with a low roughness depth can be effectively inactivated. Peracetic acid proved to be the most effective disinfectant across all tests. Regardless of the pathogen and the type of wood, a concentration of 0.1% of the pure substance at a temperature of 10 °C and an exposure time of one hour can be recommended. At a temperature of -10 °C, a concentration of 0.75% is recommended. The basic chemicals formic acid and glutaraldehyde demonstrated only limited effectiveness overall. The synergistic effects of various wood components on the inactivation of viruses offer potential for further investigation. Disinfectant tests should also be conclusively verified in field trials to ensure that the results from standardised laboratory tests can be transferred to real stable conditions.

9.
Viruses ; 16(5)2024 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-38793669

RESUMO

The aim of this study was to analyse the hygienic suitability of wood often used in animal husbandry. To this end, the inactivation of viruses (Enterovirus E as a surrogate for non-enveloped viruses and Newcastle disease virus as a surrogate for enveloped viruses) on germ carriers consisting of various types of wood was studied over an extended period to assess the biosafety of wood as an agricultural building material. The study was designed to assess the intrinsic biocidal activity of the wood itself, without the use of a disinfectant. The laboratory tests were based on German test guidelines and current European standards. Five different types of wood germ carriers, i.e., spruce (Picea abies), pine (Pinus sylvestris), poplar (Populus sp.), beech (Fagus sylvatica) and Douglas fir (Pseudotsuga menziesii), as well as stainless-steel carriers, were inoculated with enveloped and non-enveloped viruses and stored for up to four months, and the remaining infectivity of the viruses was continuously assessed. The results showed that intact, finely sawn timber with a low depth of roughness had an inactivating effect on the viruses up to 7.5 decadal logarithmic levels. For the non-enveloped virus, inactivation was fastest on Douglas fir wood, with the target reduction for effective inactivation (reduction by factor 4.0 log10) being achieved after two weeks, and for the enveloped virus on pine wood, it was already achieved from the day of drying. The hygienic effects of the wood carriers may be due to their hygroscopic properties and wood constituents. These effects offer potential for further investigation, including tests with other wood species rich in extractives.


Assuntos
Criação de Animais Domésticos , Madeira , Madeira/virologia , Animais , Criação de Animais Domésticos/métodos , Inativação de Vírus
10.
J Prosthet Dent ; 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38797573

RESUMO

STATEMENT OF PROBLEM: Interest is growing in immediately loading definitive implant-supported prostheses. However, it appears that implant protocols are evolving faster than their scientific validation. PURPOSE: The purpose of this scoping review was to identify the current trends, feasibility, and clinical outcomes of a specific clinical loading scenario (type A), where a single definitive implant-retained restoration is delivered within 3 days. The focus question was "In partially edentulous patients requiring an implant-retained prosthesis (population), is immediate loading with a definitive restoration (concept) a viable treatment option (context)?" MATERIAL AND METHODS: An electronic search was conducted in the PubMed, CENTRAL, Scopus, Embase, and Web of Science databases. Two authors independently reviewed the studies, screened titles and abstracts, and performed full-text analysis. Cross-reference checks within the bibliography of included studies, relevant reviews, and guideline were conducted. Bibliometric information and study details were extracted. RESULTS: The search identified 2568 titles after removing duplicates. Four studies involving 91 participant and 100 implant-retained restorations were included in this scoping review. The selected articles were a randomized controlled trial (RCT), a prospective clinical study, and the remaining 2 were case series. The follow-up periods investigated ranged from 6 to 26 months. All studies evaluated marginal bone loss as a primary outcome, and only 1 implant failure was reported. Patient-reported outcome measures were favorable, and no major biological or technical complications were reported in any study. CONCLUSIONS: Immediate loading with a definitive restoration within 3 days appears to be a suitable approach in specific clinical situations.

11.
Int J Comput Dent ; 0(0): 1-35, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38801193

RESUMO

AIM: The aim of this scoping review was to identify the scientific evidence related to the utilization of Optical See- Through Head-Mounted Display (OST-HMD) in dentistry, and to determine future research needs. METHODS: The research question was formulated using the "Population" (P), "Concept" (Cpt), and "Context" (Cxt) framework for scoping reviews. Existing literature was designated as P, OST-HMD as Cpt, and Dentistry as Cxt. An electronic search was conducted in PubMed, Embase, Web of Science, and CENTRAL. Two authors independently screened titles and abstracts and performed the full-text analysis. RESULTS: The search identified 286 titles after removing duplicates. Nine studies, involving 138 participants and 1760 performed tests were included in this scoping review. Seven of the articles were preclinical studies, one was a survey, and one was a clinical trial. The included manuscripts covered various dental fields: three studies in orthodontics, two in oral surgery, two in conservative dentistry, one in general dentistry, and the remaining one in prosthodontics. Five articles focused on educational purposes. Two brands of OST-HMD were used: in eight studies HoloLens Microsoft was used, while Google Glass was utilized in one article. CONCLUSIONS: The overall number of included studies was low; therefore, the available data from this review cannot yet support an evidence-based recommendation for the clinical use of OST-HMDs. However, the existing preclinical data indicate a significant capacity for clinical and educational implementation. Further adoption of these devices will facilitate more reliable and objective quality and performance assessments, as well as more direct comparisons with conventional workflows. More clinical studies must be conducted to substantiate the potential benefits and reliability for patients and clinicians.

12.
Animals (Basel) ; 14(10)2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38791626

RESUMO

Camera traps are becoming widely used for wildlife monitoring and management. However, manual analysis of the resulting image sets is labor-intensive, time-consuming and costly. This study shows that automated computer vision techniques can be extremely helpful in this regard, as they can rapidly and automatically extract valuable information from the images. Specific training with a set of 1600 images obtained from a study where wild animals approaching wild boar carcasses were monitored enabled the model to detect five different classes of animals automatically in their natural environment with a mean average precision of 98.11%, namely 'wild boar', 'fox', 'raccoon dog', 'deer' and 'bird'. In addition, sequences of images were automatically analyzed and the number of wild boar visits and respective group sizes were determined. This study may help to improve and speed up the monitoring of the potential spread of African swine fever virus in areas where wild boar are affected.

13.
Artigo em Inglês | MEDLINE | ID: mdl-38761187

RESUMO

PURPOSE: Penile cancer is a rare entity and has a good prognosis in localized stage. Delayed surgical treatment of lymphatic disease is associated with poor overall survival but conventional imaging cannot detect occult lymph node metastasis sufficiently. Imaging cancer related fibroblasts has shown promising results as non-invasive staging tool in various tumor entities but has not yet been evaluated in penile cancer. METHODS: In this single-center pilot study, patients planned for surgical treatment for penile cancer underwent preoperatively [68Ga]Ga-FAPI-46 PET/CT. Post-operative histopathology was compared to [68Ga]Ga-FAPI-46 PET/CT results. RESULTS: From January 2022 to June 2022, a total number 11 patients with histopathologically proven penile cancer underwent surgery and received [68Ga]Ga-FAPI-46 PET/CT prior therapy. 8 primary tumor sites and 4 lymph node regions were analyzed. FAPI uptake was increased on primary tumor site (SUVmax 16.2 (9.1 - 25.8)). Histopathological proven lymph node regions showed highly increased FAPI uptakes (SUVmax 17.9 (16.4 - 23.5) on [68Ga]Ga-FAPI-46 PET/CT. CONCLUSION: In this first pilot cohort, there were no false-positive FAPI uptake which might allow the detection of occult lymph node metastasis by [68Ga]Ga-FAPI-46 PET/CT and might consequently lead to omitting lymph node regions during surgery that had no increased FAPI uptake pre-operatively.

14.
PLoS One ; 19(4): e0297867, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38603730

RESUMO

We sequenced and comprehensively analysed the genomic architecture of 98 fluorescent pseudomonads isolated from different symptomatic and asymptomatic tissues of almond and a few other Prunus spp. Phylogenomic analyses, genome mining, field pathogenicity tests, and in vitro ice nucleation and antibiotic sensitivity tests were integrated to improve knowledge of the biology and management of bacterial blast and bacterial canker of almond. We identified Pseudomonas syringae pv. syringae, P. cerasi, and P. viridiflava as almond canker pathogens. P. syringae pv. syringae caused both canker and foliar (blast) symptoms. In contrast, P. cerasi and P. viridiflava only caused cankers, and P. viridiflava appeared to be a weak pathogen of almond. Isolates belonging to P. syringae pv. syringae were the most frequently isolated among the pathogenic species/pathovars, composing 75% of all pathogenic isolates. P. cerasi and P. viridiflava isolates composed 8.3 and 16.7% of the pathogenic isolates, respectively. Laboratory leaf infiltration bioassays produced results distinct from experiments in the field with both P. cerasi and P. syringae pv. syringae, causing significant necrosis and browning of detached leaves, whereas P. viridiflava conferred moderate effects. Genome mining revealed the absence of key epiphytic fitness-related genes in P. cerasi and P. viridiflava genomic sequences, which could explain the contrasting field and laboratory bioassay results. P. syringae pv. syringae and P. cerasi isolates harboured the ice nucleation protein, which correlated with the ice nucleation phenotype. Results of sensitivity tests to copper and kasugamycin showed a strong linkage to putative resistance genes. Isolates harbouring the ctpV gene showed resistance to copper up to 600 µg/ml. In contrast, isolates without the ctpV gene could not grow on nutrient agar amended with 200 µg/ml copper, suggesting ctpV can be used to phenotype copper resistance. All isolates were sensitive to kasugamycin at the label-recommended rate of 100µg/ml.


Assuntos
Prunus dulcis , Pseudomonas syringae , Pseudomonas , Cobre , Genômica , Gelo , Filogenia , Prunus dulcis/genética
16.
Rev Sci Instrum ; 95(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38517257

RESUMO

We present a method for the reconstruction of ion kinetic energy distributions from ion time-of-flight mass spectra through ion trajectory simulations. In particular, this method is applicable to complicated spectrometer geometries with largely anisotropic ion collection efficiencies. A calibration procedure using a single ion mass peak allows the accurate determination of parameters related to the spectrometer calibration, experimental alignment, and instrument response function, which improves the agreement between simulations and experiment. The calibrated simulation is used to generate a set of basis functions for the time-of-flight spectra, which are then used to transform from time-of-flight to kinetic-energy spectra. We demonstrate this reconstruction method on a recent pump-probe experiment by Asmussen et al. [Asmussen et al., Phys. Chem. Chem. Phys., 23, 15138, (2021)] on helium nanodroplets and retrieve time-resolved kinetic-energy-release spectra for the ions from ion time-of-flight spectra.

17.
Clin Implant Dent Relat Res ; 26(3): 554-563, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38419210

RESUMO

AIM: To investigate whether the lack of keratinized mucosa (KM) affects peri-implant health after 10 years of loading. MATERIALS AND METHODS: Data from 74 patients with 148 implants from two randomized controlled studies comparing different implant systems were included and analyzed. Clinical parameters including bleeding on probing (BOP), probing depth (PD), plaque index, marginal bone loss (MBL), and KM width (KMW) at buccal sites were collected at baseline (time of the final prosthesis insertion), 5-year and 10 years postloading. Multivariable logistic and linear regression models by means of a generalized estimated equation (GEE) were used to evaluate the influence of buccal KM on peri-implant clinical parameters; BOP, MBL, PD, and adjusted for implant type (one-piece or two-piece) and compliance. RESULTS: A total of 35 (24.8%) implants were healthy, 67 (47.5%) had mucositis and 39 (27.6%) were affected by peri-implantitis. In absence of buccal KM (KM = 0 mm), 75% of the implants exhibited mucositis, while in the presence of KM (KMW >0 mm) 41.2% exhibited mucositis. Regarding peri-implantitis, the corresponding percentages were 20% (KM = 0 mm) and 26.7% (KM >0 mm). Unadjusted logistic regression showed that the presence of buccal KM tended to reduce the odds of showing BOP at buccal sites (OR: 0.28 [95% CI, 0.07 to 1.09], p = 0.06). The adjusted logistic regression model revealed that having buccal KM (OR: 0.21 [95% CI, 0.05 to 0.85], p = 0.02) and using two-piece implants (OR: 0.34 [95% CI, 0.15 to 0.75], p = 0.008) significantly reduced the odds of showing BOP. Adjusted linear regression by means of GEE showed that KM and two-piece implants were associated with reduced MBL and MBL changes (p < 0.05). CONCLUSION: The lack of buccal KM appears to be linked with peri-implant parameters such as BOP and MBL, but the association is weak. The design of one-piece implants may account for their increased odds of exhibiting BOP.


Assuntos
Implantes Dentários , Mucosa Bucal , Peri-Implantite , Humanos , Estudos Prospectivos , Feminino , Masculino , Peri-Implantite/etiologia , Implantes Dentários/efeitos adversos , Pessoa de Meia-Idade , Queratinas , Perda do Osso Alveolar/etiologia , Índice Periodontal , Idoso , Índice de Placa Dentária , Implantação Dentária Endóssea/efeitos adversos , Implantação Dentária Endóssea/métodos , Mucosite/etiologia , Estomatite/etiologia
18.
Nat Commun ; 15(1): 1165, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326311

RESUMO

The t(X,17) chromosomal translocation, generating the ASPSCR1::TFE3 fusion oncoprotein, is the singular genetic driver of alveolar soft part sarcoma (ASPS) and some Xp11-rearranged renal cell carcinomas (RCCs), frustrating efforts to identify therapeutic targets for these rare cancers. Here, proteomic analysis identifies VCP/p97, an AAA+ ATPase with known segregase function, as strongly enriched in co-immunoprecipitated nuclear complexes with ASPSCR1::TFE3. We demonstrate that VCP is a likely obligate co-factor of ASPSCR1::TFE3, one of the only such fusion oncoprotein co-factors identified in cancer biology. Specifically, VCP co-distributes with ASPSCR1::TFE3 across chromatin in association with enhancers genome-wide. VCP presence, its hexameric assembly, and its enzymatic function orchestrate the oncogenic transcriptional signature of ASPSCR1::TFE3, by facilitating assembly of higher-order chromatin conformation structures demonstrated by HiChIP. Finally, ASPSCR1::TFE3 and VCP demonstrate co-dependence for cancer cell proliferation and tumorigenesis in vitro and in ASPS and RCC mouse models, underscoring VCP's potential as a novel therapeutic target.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Animais , Camundongos , Humanos , Proteômica , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Translocação Genética , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Neoplasias Renais/genética , Cromatina/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Cromossomos Humanos X/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteína com Valosina/genética
19.
JAMA Dermatol ; 160(3): 303-311, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38324293

RESUMO

Importance: The development of artificial intelligence (AI)-based melanoma classifiers typically calls for large, centralized datasets, requiring hospitals to give away their patient data, which raises serious privacy concerns. To address this concern, decentralized federated learning has been proposed, where classifier development is distributed across hospitals. Objective: To investigate whether a more privacy-preserving federated learning approach can achieve comparable diagnostic performance to a classical centralized (ie, single-model) and ensemble learning approach for AI-based melanoma diagnostics. Design, Setting, and Participants: This multicentric, single-arm diagnostic study developed a federated model for melanoma-nevus classification using histopathological whole-slide images prospectively acquired at 6 German university hospitals between April 2021 and February 2023 and benchmarked it using both a holdout and an external test dataset. Data analysis was performed from February to April 2023. Exposures: All whole-slide images were retrospectively analyzed by an AI-based classifier without influencing routine clinical care. Main Outcomes and Measures: The area under the receiver operating characteristic curve (AUROC) served as the primary end point for evaluating the diagnostic performance. Secondary end points included balanced accuracy, sensitivity, and specificity. Results: The study included 1025 whole-slide images of clinically melanoma-suspicious skin lesions from 923 patients, consisting of 388 histopathologically confirmed invasive melanomas and 637 nevi. The median (range) age at diagnosis was 58 (18-95) years for the training set, 57 (18-93) years for the holdout test dataset, and 61 (18-95) years for the external test dataset; the median (range) Breslow thickness was 0.70 (0.10-34.00) mm, 0.70 (0.20-14.40) mm, and 0.80 (0.30-20.00) mm, respectively. The federated approach (0.8579; 95% CI, 0.7693-0.9299) performed significantly worse than the classical centralized approach (0.9024; 95% CI, 0.8379-0.9565) in terms of AUROC on a holdout test dataset (pairwise Wilcoxon signed-rank, P < .001) but performed significantly better (0.9126; 95% CI, 0.8810-0.9412) than the classical centralized approach (0.9045; 95% CI, 0.8701-0.9331) on an external test dataset (pairwise Wilcoxon signed-rank, P < .001). Notably, the federated approach performed significantly worse than the ensemble approach on both the holdout (0.8867; 95% CI, 0.8103-0.9481) and external test dataset (0.9227; 95% CI, 0.8941-0.9479). Conclusions and Relevance: The findings of this diagnostic study suggest that federated learning is a viable approach for the binary classification of invasive melanomas and nevi on a clinically representative distributed dataset. Federated learning can improve privacy protection in AI-based melanoma diagnostics while simultaneously promoting collaboration across institutions and countries. Moreover, it may have the potential to be extended to other image classification tasks in digital cancer histopathology and beyond.


Assuntos
Dermatologia , Melanoma , Nevo , Neoplasias Cutâneas , Humanos , Melanoma/diagnóstico , Inteligência Artificial , Estudos Retrospectivos , Neoplasias Cutâneas/diagnóstico , Nevo/diagnóstico
20.
PLoS Comput Biol ; 20(1): e1011840, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38289971

RESUMO

Learning from past experience is an important adaptation and theoretical models may help to understand its evolution. Many of the existing models study simple phenotypes and do not consider the mechanisms underlying learning while the more complex neural network models often make biologically unrealistic assumptions and rarely consider evolutionary questions. Here, we present a novel way of modelling learning using small neural networks and a simple, biology-inspired learning algorithm. Learning affects only part of the network, and it is governed by the difference between expectations and reality. We use this model to study the evolution of learning under various environmental conditions and different scenarios for the trade-off between exploration (learning) and exploitation (foraging). Efficient learning readily evolves in our individual-based simulations. However, in line with previous studies, the evolution of learning is less likely in relatively constant environments, where genetic adaptation alone can lead to efficient foraging, or in short-lived organisms that cannot afford to spend much of their lifetime on exploration. Once learning does evolve, the characteristics of the learning strategy (i.e. the duration of the learning period and the learning rate) and the average performance after learning are surprisingly little affected by the frequency and/or magnitude of environmental change. In contrast, an organism's lifespan and the distribution of resources in the environment have a clear effect on the evolved learning strategy: a shorter lifespan or a broader resource distribution lead to fewer learning episodes and larger learning rates. Interestingly, a longer learning period does not always lead to better performance, indicating that the evolved neural networks differ in the effectiveness of learning. Overall, however, we show that a biologically inspired, yet relatively simple, learning mechanism can evolve to lead to an efficient adaptation in a changing environment.


Assuntos
Evolução Biológica , Redes Neurais de Computação , Fenótipo , Algoritmos , Modelos Biológicos
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