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Adjacent plant cells are connected by specialized cell wall regions, called middle lamellae, which influence critical agricultural characteristics, including fruit ripening and organ abscission. Middle lamellae are enriched in pectin polysaccharides, specifically homogalacturonan (HG). Here, we identify a plant-specific Arabidopsis DUF1068 protein, called NKS1/ELMO4, that is required for middle lamellae integrity and cell adhesion. NKS1 localizes to the Golgi apparatus and loss of NKS1 results in changes to Golgi structure and function. The nks1 mutants also display HG deficient phenotypes, including reduced seedling growth, changes to cell wall composition, and tissue integrity defects. These phenotypes are comparable to qua1 and qua2 mutants, which are defective in HG biosynthesis. Notably, genetic interactions indicate that NKS1 and the QUAs work in a common pathway. Protein interaction analyses and modeling corroborate that they work together in a stable protein complex with other pectin-related proteins. We propose that NKS1 is an integral part of a large pectin synthesis protein complex and that proper function of this complex is important to support Golgi structure and function.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Adesão Celular/genética , Pectinas/metabolismo , Complexo de Golgi/genética , Complexo de Golgi/metabolismo , Parede Celular/metabolismoRESUMO
The face is a defining feature of our individuality, crucial for our social interactions. But what happens when the face connected to the self is radically altered or replaced? We address the plasticity of self-face recognition in the context of facial transplantation. While the acquisition of a new face following facial transplantation is a medical fact, the experience of a new identity is an unexplored psychological outcome. We traced the changes in self-face recognition before and after facial transplantation to understand if and how the transplanted face gradually comes to be perceived and recognized as the recipient's own new face. Neurobehavioral evidence documents a strong representation of the pre-injury appearance pre-operatively, while following the transplantation, the recipient incorporates the new face into his self-identity. The acquisition of this new facial identity is supported by neural activity in medial frontal regions that are considered to integrate psychological and perceptual aspects of the self.
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Reconhecimento Facial , Transplante de Face , Face , Individualidade , Reconhecimento Visual de Modelos , Expressão FacialRESUMO
BACKGROUND: Carcass weight (HCW) and marbling (MARB) are critical for meat quality and market value in beef cattle. In composite breeds like Brangus, which meld the genetics of Angus and Brahman, SNP-based analyses have illuminated some genetic influences on these traits, but they fall short in fully capturing the nuanced effects of breed of origin alleles (BOA) on these traits. Focus on the impacts of BOA on phenotypic features within Brangus populations can result in a more profound understanding of the specific influences of Angus and Brahman genetics. Moreover, the consideration of BOA becomes particularly significant when evaluating dominance effects contributing to heterosis in crossbred populations. BOA provides a more comprehensive measure of heterosis due to its ability to differentiate the distinct genetic contributions originating from each parent breed. This detailed understanding of genetic effects is essential for making informed breeding decisions to optimize the benefits of heterosis in composite breeds like Brangus. OBJECTIVE: This study aims to identify quantitative trait loci (QTL) influencing HCW and MARB by utilizing SNP and BOA information, incorporating additive, dominance, and overdominance effects within a multi-generational Brangus commercial herd. METHODS: We analyzed phenotypic data from 1,066 genotyped Brangus steers. BOA inference was performed using LAMP-LD software using Angus and Brahman reference sets. SNP-based and BOA-based GWAS were then conducted considering additive, dominance, and overdominance models. RESULTS: The study identified numerous QTLs for HCW and MARB. A notable QTL for HCW was associated to the SGCB gene, pivotal for muscle growth, and was identified solely in the BOA GWAS. Several BOA GWAS QTLs exhibited a dominance effect underscoring their importance in estimating heterosis. CONCLUSIONS: Our findings demonstrate that SNP-based methods may not detect all genetic variation affecting economically important traits in composite breeds. BOA inclusion in genomic evaluations is crucial for identifying genetic regions contributing to trait variation and for understanding the dominance value underpinning heterosis. By considering BOA, we gain a deeper understanding of genetic interactions and heterosis, which is integral to advancing breeding programs. The incorporation of BOA is recommended for comprehensive genomic evaluations to optimize trait improvements in crossbred cattle populations.
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Cruzamento , Estudo de Associação Genômica Ampla , Fenótipo , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Animais , Bovinos/genética , Genótipo , Vigor Híbrido , Carne , AlelosRESUMO
BACKGROUND: Cervical cancer incidence is rising in Puerto Rico (PR). Whether the increase is real or reflective of increased diagnostic scrutiny remains unclear. METHODS: Using data from the PR Central Cancer Registry for 2001-2019, we estimated trends of hysterectomy-corrected cervical cancer incidence and mortality rates, overall, and by stage at diagnosis and age. RESULTS: Overall, cervical cancer incidence (per 100,000) increased 1.6%/year (95% CI, -0.5% to 3.8%) from 12.5 to 15.3, with a prominent increase in distant-stage disease (4.5%/year [95% CI, 1.6% to 8.0%]), particularly among screening age eligible (25-64-year-old) women (5.8%/year [95% CI, 2.1% to 10.6%]). Mortality rates in this age-group remained stable during the study period. CONCLUSIONS: Increased occurrence of distant-stage disease among screening-eligible women is troubling and may reflect a real increase. Future research is needed to elucidate the factors underlying these trends. Improved prevention is also an urgent priority to reverse the rising cervical cancer incidence in PR.
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Neoplasias do Colo do Útero , Humanos , Feminino , Porto Rico/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/mortalidade , Incidência , Pessoa de Meia-Idade , Adulto , Idoso , Adulto Jovem , Estadiamento de Neoplasias , Adolescente , Sistema de RegistrosRESUMO
BACKGROUND: Colonoscopy is a diagnostic and therapeutic procedure that reduces colorectal cancer incidence and mortality but requires adequate bowel cleansing for high-quality examination. Past studies have suggested cirrhosis as a risk factor for worse bowel preparation. METHODS: We carried out a match-controlled retrospective study evaluating patients with and without cirrhosis who underwent outpatient screening colonoscopies to assess the effect of cirrhosis and portal hypertension complications on preparation quality and endoscopic measures. We also did a subgroup analysis excluding patients with obesity. RESULTS: We examined 1464 patients with cirrhosis and matched controls. Cirrhotic patients had lower mean Boston Bowel Preparation Scale (BBPS) scores and slower cecal intubation times. We found a single point increase in the Model for End-stage Liver Disease (MELD) score, as well as ascites, hepatic encephalopathy, and variceal hemorrhage were all associated with a longer cecal intubation time. Subgroup analysis excluding patients with obesity again found a significantly lower BBPS score and longer cecal intubation time while also finding a 24% drop in polyp detection. CONCLUSIONS: Patients with cirrhosis have worse BBPS scores and longer cecal intubation times. Nonobese cirrhotic patients additionally have a lower polyp detection rate. Portal hypertension complications were associated with worsened preparation quality and longer cecal intubation times. Each incremental increase in MELD score lengthened cecal intubation time. These findings support a more aggressive bowel preparation strategy for patients with cirrhosis, especially patients with severe disease or portal hypertension complications.
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Immune checkpoint inhibitor (ICI) immunotherapy leverages the body's own immune system to attack cancer cells but leads to unwanted autoimmune side effects in up to 60% of patients. Such immune-related adverse events (IrAEs) may lead to treatment interruption, permanent organ dysfunction, hospitalization, and premature death. Thyroiditis is one of the most common IrAEs, but the cause of thyroid IrAEs remains unknown. In this study, we use a new, physiologically relevant mouse model of ICI-associated autoimmunity to identify a key role for type 3 immune cells in the development of thyroid IrAEs. Multiple lineages of IL-17A-producing T cells expand in thyroid tissue with ICI treatment. Intrathyroidal IL-17A-producing innate-like γδT17 cells were increased in tumor-free mice, whereas adaptive Th17 cells were also prominent in tumor-bearing mice, following ICI treatment. Furthermore, Ab-based inhibition of IL-17A, a clinically available therapy, significantly reduced thyroid IrAE development in ICI-treated mice with and without tumor challenge. Finally, combination of IL-17A neutralization with ICI treatment in multiple tumor models did not reduce ICI antitumor efficacy. These studies suggest that targeting Th17 and γδT17 cell function via the IL-17A axis may reduce IrAEs without impairing ICI antitumor efficacy and may be a generalizable strategy to address type 3 immune-mediated IrAEs.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Neoplasias , Animais , Imunoterapia , Interleucina-17 , Camundongos , Neoplasias/patologia , Glândula Tireoide/patologiaRESUMO
PURPOSE: To identify and quantify the reasons why acute coronary syndrome (ACS) patients undergoing stenting at the University of New Mexico Hospital (UNMH) were prescribed sub-optimal dual antiplatelet therapy (DAPT) at discharge, and to identify practice patterns that could potentially lead to improved DAPT treatment for these patients. METHODS: We reviewed electronic medical records and cardiac catheterization records of 326 patients who underwent percutaneous coronary intervention (PCI) at UNMH between January 1, 2021, and June 30, 2022 and identified 229 ACS patients who survived until discharge. Demographic and clinical characteristics relevant to P2Y12 inhibitor selection were obtained from a review of medical records. Pharmacists' notes documenting their efforts to secure appropriate insurance coverage and reasons for discharging patients on clopidogrel rather than ticagrelor/prasugrel were reviewed. Patients discharged on aspirin and clopidogrel underwent review of medical records and cardiac catheterization lab records to determine if the discharge P2Y12 drug was appropriate. Reasons for inappropriate discharge on clopidogrel were categorized as cost/insurance, patient preference, concern for daily adherence to a twice-daily medication, and maintenance of pre-hospital clopidogrel therapy rather than switch to ticagrelor after PCI. RESULTS: The 229 ACS patients included 87 (38.0%) appropriately discharged on ticagrelor/prasugrel, 63 (27.5%) appropriately discharged on clopidogrel, 75 (32.8%) discharged on sub-optimal clopidogrel, and 4 (1.7%) not discharged on a P2Y12 inhibitor. For patients inappropriately discharged on clopidogrel (n = 75), the most common reasons were cost or lack of insurance (n = 56) and clinical inertia (taking clopidogrel before PCI and maintained on it afterward) (n = 17). Sub-optimal P2Y12 therapy at discharge was significantly associated with lack of insurance (odds ratio 21.5, 95% confidence interval 5.33-156,p < 0.001) but not with ethnicity, age, sex, or diabetes. CONCLUSION: At the University of New Mexico, a safety-net hospital, increasing financially restricted access to ticagrelor/prasugrel could help up to 24.5% of ACS patients reduce their risk of ischemic events. For patients admitted on clopidogrel DAPT, escalating to ticagrelor/prasugrel could reduce ischemic risk in 7.4%. Expanding and improving healthcare insurance coverage might reduce the frequency of discharge on sub-optimal P2Y12 therapy.
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As innovations in the field of vascular composite allotransplantation (VCA) progress, whole-eye transplantation (WET) is poised to transition from non-human mammalian models to living human recipients. Present treatment options for vision loss are generally considered suboptimal, and attendant concerns ranging from aesthetics and prosthesis maintenance to social stigma may be mitigated by WET. Potential benefits to WET recipients may also include partial vision restoration, psychosocial benefits related to identity and social integration, improvements in physical comfort and function, and reduced surgical risk associated with a biologic eye compared to a prosthesis. Perioperative and postoperative risks of WET are expected to be comparable to those of facial transplantation (FT), and may be similarly mitigated by immunosuppressive protocols, adequate psychosocial support, and a thorough selection process for both the recipient and donor. To minimize the risks associated with immunosuppressive medications, the first attempts in human recipients will likely be performed in conjunction with a FT. If first-in-human attempts at combined FT-WET prove successful and the biologic eye survives, this opens the door for further advancement in the field of vision restoration by means of a viable surgical option. This analysis integrates recent innovations in WET research with the existing discourse on the ethics of surgical innovation and offers preliminary guidance to VCA programs considering undertaking WET in human recipients.
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Produtos Biológicos , Alotransplante de Tecidos Compostos Vascularizados , Animais , Humanos , Alotransplante de Tecidos Compostos Vascularizados/métodos , Imunossupressores , MamíferosRESUMO
INTRODUCTION: Facial masculinization surgery (FMS) is increasingly popular among cisgender and transgender men. The benefits of FMS are focused on facial identity and have been proven to decrease gender dysphoria in this population. Previous research showed increasing interest in gender affirmation surgery and facial feminization surgery, but the prevalence of FMS has not been explored. It is difficult to find these data based on surgical records alone because institutions do not have standardized methods of reporting and lack publications in the field. Our study aimed to analyze public interest in FMS by using worldwide Google Trends to quantify these trends. METHODS: A worldwide Google Trends search was completed from January 1, 2008, to December 31, 2022, for terms focused on FMS. Then, search terms were analyzed for nonfacial masculinization procedures and were aggregated. Lastly, a PubMed search was conducted for the terms "transgender" and "facial masculinization" from January 1, 2008, to December 31 st , 2022, to compare publication rates. RESULTS: Our data showed an increasing interest in FMS through Google search trends since the year 2008. A similar trend was demonstrated for non-FMS gender-affirming terms. PubMed analysis showed "transgender" medicine publishing rates were approximately 39.65 times greater than "facial masculinization" publishing rates, although "facial masculinization" medicine did produce a positive trend over the study period of approximately 4 publications per year. The medical literature on transgender surgeries rapidly outpaces publications specifically focusing on FMS. CONCLUSION: Our study showed increasing interest in gender affirmation surgery over time, particularly FMS. These increasing trends should encourage greater scientific exploration of FMS and research to properly quantify and assess surgical outcomes in this special population. Additional educational interventions for both the general public and medical providers, to increase awareness of unique challenges that impact this community and highlight changes in health care coverage over time, should be created to keep pace with increasing patient demand and address the physical, systemic, and psychosocial issues faced by people who identify as transgender.
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Cirurgia de Readequação Sexual , Pessoas Transgênero , Transexualidade , Masculino , Humanos , Transexualidade/cirurgia , Pessoas Transgênero/psicologia , Face/cirurgia , Cabeça/cirurgiaRESUMO
BACKGROUND: Facial feminization surgery (FFS) is an emerging practice that falls under the broader umbrella of gender-affirming surgery. Various approaches exist to feminize the face, yet few published articles describe in detail the techniques of each component procedure. Considering the diversity of interventions employed, the objective of this manuscript is to highlight FFS techniques utilized by the senior author and create a corresponding media gallery. METHODS: All patients with the diagnosis of gender dysphoria that were referred to the senior author for FFS consultation between June 2017 and August 2022 were reviewed. Data were retrospectively collected from electronic medical records according to the institutional review board (IRB)-approved study protocol. Data collected and analyzed included demographics, operative documentation, and postoperative follow-up. Multimedia material was collected intraoperatively and postoperatively. RESULTS: A total of 231 patients underwent 262 operations with a total of 1224 FFS procedures. The average follow-up time was 7.7 ± 11 months. Out of the 262 operations, 24 (9.2%) patients experienced minor complications, including 3 (1.1%) with wound dehiscence, 13 (5.0%) with hematomas, and 14 (5.3%) with postoperative infection requiring antibiotics. Of those, 3 (1.1%) required a return to the operating room for washout or removal of malar implants. CONCLUSION: Although there is a consensus on the fundamental surgical principles to achieve adequate feminization of the facial architecture, the specific techniques to do so differ according to individual practices. As techniques diverge, so do their risk profiles and outcomes; techniques must, thus, align with patients' interventional goals. The material presented here is one of many that can support trainees and junior surgeons as they build a gender-affirming practice.
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Disforia de Gênero , Cirurgia de Readequação Sexual , Humanos , Feminino , Estudos Retrospectivos , Masculino , Disforia de Gênero/cirurgia , Adulto , Cirurgia de Readequação Sexual/métodos , Feminização , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologiaRESUMO
OBJECTIVES: For transwomen undergoing voice feminization interventions, fundamental frequency (F 0 ; vocal pitch) is a commonly reported functional outcome measure in the literature. However, F 0 may not correlate well with improvement in quality of life (QoL). Several validated voice-related QoL instruments have been used to assess QoL improvement in these patients, yet there is no consensus on the most appropriate instrument. This systematic review and meta-analysis aimed to assess the relationship between change in F 0 and QoL improvement following voice feminization, and to compare validated QoL instruments commonly used in this population. DATA SOURCES: PubMed, Cochrane, and Embase. REVIEW METHODS: A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Primary studies of transwomen undergoing voice feminization, reporting validated QoL outcomes were included. Meta-analyses for associations between mean change in QoL score and mean change in F 0 , as well as variations in mean change in QoL score by QoL instrument, were performed using a multilevel mixed effects model. RESULTS: No statistically significant correlation was found between change in F 0 and QoL score improvement post-intervention. Different validated instruments showed statistically significant variation in QoL score change, with the Trans Women Voice Questionnaire (TWVQ) capturing a greater improvement in QoL score relative to other instruments. CONCLUSIONS: Lack of correlation between changes in F 0 and QoL improvement further supports that F 0 alone is insufficient to assess the efficacy of voice feminizing interventions. Validated QoL measures are useful adjuncts. Of these, the TWVQ appears to be the most sensitive for measurement of QoL improvement following voice feminization.
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Transexualidade , Voz , Masculino , Humanos , Feminino , Qualidade de Vida , Feminização , Inquéritos e QuestionáriosRESUMO
The result of the multidisciplinary collaboration of researchers from different areas of knowledge to validate a solar radiation model is presented. The MAPsol is a 3D local-scale adaptive solar radiation model that allows us to estimate direct, diffuse, and reflected irradiance for clear sky conditions. The model includes the adaptation of the mesh to complex orography and albedo, and considers the shadows cast by the terrain and buildings. The surface mesh generation is based on surface refinement, smoothing and parameterization techniques and allows the generation of high-quality adapted meshes with a reasonable number of elements. Another key aspect of the paper is the generation of a high-resolution digital elevation model (DEM). This high-resolution DEM is constructed from LiDAR data, and its resolution is two times more accurate than the publicly available DEMs. The validation process uses direct and global solar irradiance data obtained from pyranometers at the University of Salamanca located in an urban area affected by systematic shading from nearby buildings. This work provides an efficient protocol for studying solar resources, with particular emphasis on areas of complex orography and dense buildings where shadows can potentially make solar energy production facilities less efficient.
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Viral strains, age, and host factors are associated with variable immune responses against SARS-CoV-2 and disease severity. Puerto Ricans have a genetic mixture of races: European, African, and Native American. We hypothesized that unique host proteins/pathways are associated with COVID-19 disease severity in Puerto Rico. Following IRB approval, a total of 95 unvaccinated men and women aged 21-71 years old were recruited in Puerto Rico from 2020-2021. Plasma samples were collected from COVID-19-positive subjects (n = 39) and COVID-19-negative individuals (n = 56) during acute disease. COVID-19-positive individuals were stratified based on symptomatology as follows: mild (n = 18), moderate (n = 13), and severe (n = 8). Quantitative proteomics was performed in plasma samples using tandem mass tag (TMT) labeling. Labeled peptides were subjected to LC/MS/MS and analyzed by Proteome Discoverer (version 2.5), Limma software (version 3.41.15), and Ingenuity Pathways Analysis (IPA, version 22.0.2). Cytokines were quantified using a human cytokine array. Proteomics analyses of severely affected COVID-19-positive individuals revealed 58 differentially expressed proteins. Cadherin-13, which participates in synaptogenesis, was downregulated in severe patients and validated by ELISA. Cytokine immunoassay showed that TNF-α levels decreased with disease severity. This study uncovers potential host predictors of COVID-19 severity and new avenues for treatment in Puerto Ricans.
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COVID-19 , Proteômica , SARS-CoV-2 , Índice de Gravidade de Doença , Humanos , COVID-19/sangue , COVID-19/epidemiologia , COVID-19/virologia , Pessoa de Meia-Idade , Porto Rico/epidemiologia , Feminino , Masculino , Adulto , Idoso , Proteômica/métodos , Proteínas Sanguíneas/metabolismo , Proteínas Sanguíneas/análise , Adulto Jovem , Citocinas/sangue , Citocinas/metabolismo , Espectrometria de Massas em TandemRESUMO
We conducted a cross-sectional study to determine the prevalence of soil-transmitted helminthiases (STH) in areas of rural Alabama, USA, that have sanitation deficits. We enrolled 777 children; 704 submitted stool specimens and 227 a dried blood spot sample. We microscopically examined stool specimens from all 704 children by using Mini-FLOTAC for helminth eggs. We tested a subset by using molecular techniques: real-time PCR analysis for 5 STH species, TaqMan Array Cards for enteric helminths, and digital PCR for Necator americanus hookworm. We analyzed dried blood spots for Strongyloides stercoralis and Toxocara spp. roundworms by using serologic testing. Despite 12% of our cohort reporting living in homes that directly discharge untreated domestic wastewater, stool testing for STH was negative; however, 5% of dried blood spots were positive for Toxocara spp. roundworms. Survey data suggests substantial numbers of children in this region may be exposed to raw sewage, which is itself a major public health concern.
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Helmintíase , Helmintos , Criança , Animais , Humanos , Estudos Transversais , Solo/parasitologia , Alabama/epidemiologia , Helmintíase/parasitologia , Fezes/parasitologia , PrevalênciaRESUMO
Recent reports of hookworm infection in Alabama, USA, has prompted surveillance in Mississippi, given the states' similar environmental conditions. We collected stool specimens from 277 children in Rankin County, Mississippi. Kato-Katz microscopic smear, agar plate culture, and quantitative PCR indicated no soil-transmitted helminths. Nevertheless, further surveillance in other high-risk Mississippi counties is warranted.
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Helmintos , Solo , Criança , Animais , Humanos , Solo/parasitologia , Mississippi/epidemiologia , Fezes/parasitologia , Prevalência , Helmintos/genéticaRESUMO
BACKGROUND: Patients diagnosed with low-risk prostate cancer (PCa) are confronted with a difficult decision regarding whether to undergo definitive treatment or to pursue an active surveillance protocol. This is potentially further complicated by the possibility that patients and physicians may place different value on factors that influence this decision. We conducted a qualitative investigation to better understand patient and physician perceptions of factors influencing treatment decisions for low-risk PCa. METHODS: Semi-structured interviews were conducted among 43 racially and ethnically diverse patients diagnosed with low-risk PCa, who were identified through a population-based cancer registry, and 15 physicians who were selected to represent a variety of practice settings in the Greater San Francisco Bay Area. RESULTS: Patients and physicians both described several key individual (e.g., clinical) and interpersonal (e.g., healthcare communications) factors as important for treatment decision-making. Overall, physicians' perceptions largely mirrored patients' perceptions. First, we observed differences in treatment preferences by age and stage of life. At older ages, there was a preference for less invasive options. However, at younger ages, we found varying opinions among both patients and physicians. Second, patients and physicians both described concerns about side effects including physical functioning and non-physical considerations. Third, we observed differences in expectations and the level of difficulty for clinical conversations based on information needs and resources between patients and physicians. Finally, we discovered that patients and physicians perceived patients' prior knowledge and the support of family/friends as facilitators of clinical conversations. CONCLUSIONS: Our study suggests that the gap between patient and physician perceptions on the influence of clinical and communication factors on treatment decision-making is not large. The consensus we observed points to the importance of developing relevant clinical communication roadmaps as well as high quality and accessible patient education materials.
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Médicos , Neoplasias da Próstata , Masculino , Humanos , Tomada de Decisões , Neoplasias da Próstata/terapia , Relações Médico-Paciente , Pesquisa QualitativaRESUMO
BACKGROUND AND AIMS: Artificial intelligence-based computer-aid detection (CADe) devices have been recently tested in colonoscopies, increasing the adenoma detection rate (ADR), mainly in Asian populations. However, evidence for the benefit of these devices in the occidental population is still low. We tested a new CADe device, namely, ENDO-AID (OIP-1) (Olympus, Tokyo, Japan), in clinical practice. METHODS: This randomized controlled trial included 370 consecutive patients who were randomized 1:1 to CADe (n = 185) versus standard exploration (n = 185) from November 2021 to January 2022. The primary endpoint was the ADR. Advanced adenoma was defined as ≥10 mm, harboring high-grade dysplasia, or with a villous pattern. Otherwise, the adenoma was nonadvanced. ADR was assessed in both groups stratified by endoscopist ADR and colon cleansing. RESULTS: In the intention-to-treat analysis, the ADR was 55.1% (102/185) in the CADe group and 43.8% (81/185) in the control group (P = .029). Nonadvanced ADRs (54.8% vs 40.8%, P = .01) and flat ADRs (39.4 vs 24.8, P = .006), polyp detection rate (67.1% vs 51%; P = .004), and number of adenomas per colonoscopy were significantly higher in the CADe group than in the control group (median [25th-75th percentile], 1 [0-2] vs 0 [0-1.5], respectively; P = .014). No significant differences were found in serrated ADR. After stratification by endoscopist and bowel cleansing, no statistically significant differences in ADR were found. CONCLUSIONS: Colonoscopy assisted by ENDO-AID (OIP-1) increases ADR and number of adenomas per colonoscopy, suggesting it may aid in the detection of colorectal neoplastic lesions, especially because of its detection of diminutive and flat adenomas. (Clinical trial registration number: NCT04945044.).
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Adenoma , Pólipos do Colo , Neoplasias Colorretais , Pólipos , Humanos , Inteligência Artificial , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/epidemiologia , Colonoscopia , Pólipos/diagnóstico , Adenoma/diagnóstico por imagem , Adenoma/epidemiologia , Pólipos do Colo/diagnóstico por imagemRESUMO
There is a growing interest in biomedical engineering in developing procedures that provide accurate simulations of the neural response to electrical stimulus produced by implants. Moreover, recent research focuses on models that take into account individual patient characteristics. We present a phenomenological computational model that is customized with the patient's data provided by the electrically evoked compound action potential (ECAP) for simulating the neural response to electrical stimulus produced by the electrodes of cochlear implants (CIs). The model links the input currents of the electrodes to the simulated ECAP. Potentials and currents are calculated by solving the quasi-static approximation of the Maxwell equations with the finite element method (FEM). In ECAPs recording, an active electrode generates a current that elicits action potentials in the surrounding auditory nerve fibers (ANFs). The sum of these action potentials is registered by other nearby electrode. Our computational model emulates this phenomenon introducing a set of line current sources replacing the ANFs by a set of virtual neurons (VNs). To fit the ECAP amplitudes we assign a suitable weight to each VN related with the probability of an ANF to be excited. This probability is expressed by a cumulative beta distribution parameterized by two shape parameters that are calculated by means of a differential evolution algorithm (DE). Being the weights function of the current density, any change in the design of the CI affecting the current density produces changes in the weights and, therefore, in the simulated ECAP, which confers to our model a predictive capacity. The results of the validation with ECAP data from two patients are presented, achieving a satisfactory fit of the experimental data with those provided by the proposed computational model.
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Implante Coclear , Implantes Cocleares , Potenciais de Ação/fisiologia , Implante Coclear/métodos , Nervo Coclear/fisiologia , Simulação por Computador , Estimulação Elétrica , Potenciais Evocados/fisiologia , Potenciais Evocados Auditivos/fisiologia , HumanosRESUMO
BACKGROUND AND AIMS: Variation in colorectal neoplasia detection limits the effectiveness of screening colonoscopy. By evaluating neoplasia detection rates of individual colonoscopists, we aimed to quantify the effects of pre-procedural knowledge of a positive (+) multi-target stool DNA (mt-sDNA) on colonoscopy quality metrics. METHODS: We retrospectively identified physicians who performed a high volume of + mt-sDNA colonoscopies; colorectal neoplasia at post-mt-sDNA colonoscopy was recorded. These colonoscopists were stratified into quartiles based on baseline adenoma detection rates. Baseline colonoscopy adenoma detection rates and sessile serrated lesion detection rates were compared to post-mt-sDNA colonoscopy neoplasia diagnosis rates among each quartile. Withdrawal times were measured from negative exams. RESULTS: During the study period (2014-17) the highest quartile of physicians by volume of post-mt-sDNA colonoscopies were evaluated. Among thirty-five gastroenterologists, their median screening colonoscopy adenoma detection rate was 32% (IQR, 28-39%) and serrated lesion detection rate was 13% (8-15%). After + mt-sDNA, adenoma diagnosis increased to 47% (36-56%) and serrated lesion diagnosis increased to 31% (17-42%) (both p < 0.0001). Median withdrawal time increased from 10 (7-13) to 12 (10-17) minutes (p < 0.0001) and was proportionate across quartiles. After + mt-sDNA, lower baseline detectors had disproportionately higher rates of adenoma diagnosis in female versus male patients (p = 0.048) and higher serrated neoplasia diagnosis rates among all patients (p = 0.0092). CONCLUSIONS: Knowledge of + mt-sDNA enriches neoplasia diagnosis compared to average risk screening exams. Adenomatous and serrated lesion diagnosis was magnified among those with lower adenoma detection rates. Awareness of the mt-sDNA result may increase physician attention during colonoscopy. Pre-procedure knowledge of a positive mt-sDNA test improves neoplasia diagnosis rates among colonoscopists with lower baseline adenoma detection rates, independent of withdrawal time.
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Adenoma , Neoplasias Colorretais , Humanos , Masculino , Feminino , DNA de Neoplasias , Estudos Retrospectivos , Detecção Precoce de Câncer/métodos , Colonoscopia , Neoplasias Colorretais/patologia , Adenoma/patologiaRESUMO
In actinomycetes, the acyl-CoA carboxylases, including the so-called acetyl-CoA carboxylases (ACCs), are biotin-dependent enzymes that exhibit broad substrate specificity and diverse domain and subunit arrangements. Bioinformatic analyses of the Rhodococcus jostii RHA1 genome found that this microorganism contains a vast arrange of putative acyl-CoA carboxylases domains and subunits. From the thirteen putative carboxyltransferase domains, only the carboxyltransferase subunit RO01202 and the carboxyltransferase domain present in the multidomain protein RO04222 are highly similar to well-known essential ACC subunits from other actinobacteria. Mutant strains in each of these genes showed that none of these enzymes is essential for R. jostii growth in rich or in minimal media with high nitrogen concentration, presumably because of their partial overlapping activities. A mutant strain in the ro04222 gene showed a decrease in triacylglycerol and mycolic acids accumulation in rich and minimal medium, highlighting the relevance of this multidomain ACC in the biosynthesis of these lipids. On the other hand, RO01202, a carboxyltransferase domain of a putative ACC complex, whose biotin carboxylase and biotin carboxyl carrier protein domain were not yet identified, was found to be essential for R. jostii growth only in minimal medium with low nitrogen concentration. The results of this study have identified a new component of the TAG-accumulating machinery in the oleaginous R. jostii RHA1. While non-essential for growth and TAG biosynthesis in RHA1, the activity of RO04222 significantly contributes to lipogenesis during single-cell oil production. Furthermore, this study highlights the high functional diversity of ACCs in actinobacteria, particularly regarding their essentiality under different environmental conditions. KEY POINTS: ⢠R. jostii possess a remarkable heterogeneity in their acyl-carboxylase complexes. ⢠RO04222 is a multidomain acetyl-CoA carboxylase involved in lipid accumulation. ⢠RO01202 is an essential carboxyltransferase only at low nitrogen conditions.