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RATIONALE AND OBJECTIVES: To determine the role of dynamic contrast-enhanced (DCE) MRI-radiomics in predicting the International Society of Urological Pathology Grade Group (ISUP-GG) in therapy-naïve prostate cancer (PCa) patients. MATERIALS AND METHODS: In this ethics review board-approved retrospective study on two prospective clinical trials between 2017 and 2020, 73 men with suspected/confirmed PCa were included. All participants underwent multiparametric MRI. On MRI, dominant lesions (per PI-RADS) were identified. DCE-MRI radiomic features were extracted from the segmented volumes following the image biomarker standardisation initiative (IBSI) guidelines through 14 time points. Histopathology evaluation on the cognitive-fusion targeted biopsies was set as the reference standard. Univariate regression was done to evaluate potential predictors across all calculated features. Random forest imputation was used for multivariate modelling. RESULTS: 73 index lesions were reviewed. Histopathology revealed 28, 16, 13 and 16 lesions with ISUP-GG-Negative/1/2, ISUP-GG-3, ISUP-GG-4 and ISUP-GG-5, respectively. From the extracted features, total lesion enhancement (TLE), minimum enhancement intensity and Grey-Level Run Length Matrix (GLRLM) were the most significantly different parameters among ISUP-GGs (Neg/1/2 vs 3/4 vs 5). 16 features with significant cross-sectional associations with ISUP-GGs entered the multivariate analysis. The final DCE partitioning model used only four features (lesion sphericity, TLE, GLRLM and Grey-Level Zone Length Matrix). For the binarized diagnosis (ISUP-GG≤2 vs ISUP-GG>2), the accuracy reached 81%. CONCLUSION: DCE-MRI radiomics might be used as a non-invasive tool for aiding pathological grade group prediction in therapy-naïve PCa patients, potentially adding complementary information to PI-RADS for supporting tailored diagnostic pathways and treatment planning.
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RATIONALE AND OBJECTIVES: To investigate whether [18F]-FDG PET/CT-derived radiomics may correlate with driver gene mutations in non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: In this IRB-approved retrospective study, 203 patients with surgically treated NSCLC who underwent subsequent genomic analysis of the primary tumour at our institution between December 2004 and January 2014 were identified. Of those, 128 patients (mean age 62.4 ± 10.8 years; range: 35-84) received preoperative [18F]-FDG PET/CT as part of their initial staging and thus were included in the study. PET and CT image segmentation and feature extraction were performed semi-automatically with an open-source software platform (LIFEx, Version 6.30, lifexsoft.org). Molecular profiles using different next-generation sequencing (NGS) panels were collected from a web-based resource (cBioPortal.ca for Cancer genomics). Two statistical models were then built to evaluate the predictive ability of [18F]-FDG PET/CT-derived radiomics features for driver gene mutations in NSCLC. RESULTS: More than half (68/128, 53%) of all tumour samples harboured three or more gene mutations. Overall, 55% of tumour samples demonstrated a mutation in TP53, 26% of samples had alterations in KRAS and 17% in EGFR. Extensive statistical analysis resulted in moderate to good predictive ability. The highest Youden Index for TP53 was achieved using combined PET/CT features (0.70), for KRAS using PET features only (0.57) and for EGFR using CT features only (0.60). CONCLUSION: Our study demonstrated a moderate to good correlation between radiomics features and driver gene mutations in NSCLC, indicating increased predictive ability of genomic profiles using combined [18F]-FDG PET/CT-derived radiomics features.
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We aimed to determine if clinical parameters and radiomics combined with sarcopenia status derived from baseline 18F-FDG-PET/CT could predict developing metastatic disease and overall survival (OS) in gastroesophageal cancer (GEC). Patients referred for primary staging who underwent 18F-FDG-PET/CT from 2008 to 2019 were evaluated retrospectively. Overall, 243 GEC patients (mean age = 64) were enrolled. Clinical, histopathology, and sarcopenia data were obtained, and primary tumor radiomics features were extracted. For classification (early-stage vs. advanced disease), the association of the studied parameters was evaluated. Various clinical and radiomics models were developed and assessed. Accuracy and area under the curve (AUC) were calculated. For OS prediction, univariable and multivariable Cox analyses were performed. The best model included PET/CT radiomics features, clinical data, and sarcopenia score (accuracy = 80%; AUC = 88%). For OS prediction, various clinical, CT, and PET features entered the multivariable analysis. Three clinical factors (advanced disease, age ≥ 70 and ECOG ≥ 2), along with one CT-derived and one PET-derived radiomics feature, retained their significance. Overall, 18F-FDG PET/CT radiomics seems to have a potential added value in identifying GEC patients with advanced disease and may enhance the performance of baseline clinical parameters. These features may also have a prognostic value for OS, improving the decision-making for GEC patients.
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We aimed to investigate whether [18F]F-FDG-PET/CT-derived radiomics can classify histologic subtypes and determine the anatomical origin of various malignancies. In this IRB-approved retrospective study, 391 patients (age = 66.7 ± 11.2) with pulmonary (n = 142), gastroesophageal (n = 128) and head and neck (n = 121) malignancies were included. Image segmentation and feature extraction were performed semi-automatically. Two models (all possible subset regression [APS] and recursive partitioning) were employed to predict histology (squamous cell carcinoma [SCC; n = 219] vs. adenocarcinoma [AC; n = 172]), the anatomical origin, and histology plus anatomical origin. The recursive partitioning algorithm outperformed APS to determine histology (sensitivity 0.90 vs. 0.73; specificity 0.77 vs. 0.65). The recursive partitioning algorithm also revealed good predictive ability regarding anatomical origin. Particularly, pulmonary malignancies were identified with high accuracy (sensitivity 0.93; specificity 0.98). Finally, a model for the synchronous prediction of histology and anatomical disease origin resulted in high accuracy in determining gastroesophageal AC (sensitivity 0.88; specificity 0.92), pulmonary AC (sensitivity 0.89; specificity 0.88) and head and neck SCC (sensitivity 0.91; specificity 0.92). Adding PET-features was associated with marginal incremental value for both the prediction of histology and origin in the APS model. Overall, our study demonstrated a good predictive ability to determine patients' histology and anatomical origin using [18F]F-FDG-PET/CT-derived radiomics features, mainly from CT.
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This study aimed to compare the detection of neuroendocrine tumor liver metastases (NLMs) in hepatobiliary-specific contrast-enhanced MRI (pMR) versus 68Ga-DOTATATE PET/CT (DT-PET). This retrospective study cohort included 30 patients with well-differentiated neuroendocrine tumors who underwent both DT-PET and pMR. Two readers independently assessed NLMs count, SUVmax on DT-PET, and signal characteristics on pMR. A consensus review by two additional readers resolved discrepancies between the modalities. Results showed concordance between DT-PET and pMR NLM count in 14/30 patients (47%). pMR identified more NLMs in 12/30 patients (40%), of which 4 patients showed multiple deposits on pMR but only 0-1 lesions on DT-PET. DT-PET detected more in 4/30 patients (13%). Overall, pMR detected more metastases than DT-PET (p = 0.01). Excluding the four outliers, there was excellent agreement between the two methods (ICC: 0.945, 95%CI: 0.930, 0.958). Notably, pMR had a higher NLM detection rate than DT-PET, with correlations found between lesion size on pMR and DT-PET detectability, as well as diffusion restriction on pMR and SUVmax on DT-PET. In conclusion, in consecutive patients with well-differentiated NETs, the detection rate of NLM is higher with pMR than with DT-PET. However, when excluding patients whose tumors do not overexpress somatostatin receptors (13% of the cohort), high concordance in the detection of NLM is observed between DT PET and pMR.
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Gadolinio DTPA , Neoplasias Hepáticas , Tumores Neuroendocrinos , Tomografía de Emisión de Positrones , Cintigrafía , Humanos , Radioisótopos de Galio , Tumores Neuroendocrinos/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Electrones , Estudios Retrospectivos , Imagen por Resonancia Magnética , Neoplasias Hepáticas/diagnóstico por imagenRESUMEN
PURPOSE: The main purpose of our study is to compare the adverse events occurrence, complications, and postoperative outcomes of Femtosecond Laser-Assisted Cataract Surgery (FLACS) versus conventional phacoemulsification surgery (CPS) in adult patients undergoing cataract surgery. METHODS: We conducted our research using PubMed, Scopus, and MEDLINE through EBSCOhost from 2012 to July 2022 with English and Spanish language restriction, including only Randomized Controlled Trials (RCTs). The PRISMA guidelines were observed for data abstraction, including a random-effects model for each outcome. RESULTS: We analyzed 4844 eyes from 23 RCTs with some low risk of bias according to RoB 2 tool. We found statistically significant differences between the FLACS and CPS groups for the mean absolute error (MD = -0.12, 95% CI:-0.22-[-0.02], p = 0.01), the circularity of capsulorhexis (MD = 0.04, 95% CI: 0.04-0.05, p ≤ 0.00001), IOL centration (D = -0.07, 95% CI:-0.09-[-0.05], p ≤ 0.00001), CDE count (MD = -1.75, 95% CI: -2.75-[-0.74], p = 0.0006), mean phacoemulsification time (MD = -12.90, 95% CI:-20.89-[-4.92], p = 0.002), EPT (MD = -0.93, 95% CI: -1.68-[-0.019], p = 0.01) and endothelial cell density loss ((MD = -0.6, 95% CI: -1-[-0.19], p = 0.004). Also, the safety analysis showed a lower incidence of posterior capsule tear (PCT) in the FLACS group (OR =0.29, 95% CI: 0.09-1, p = 0.05). CONCLUSIONS: Our results suggest that FLACS might be helpful for patients with relatively dense cataracts and low preoperative endothelial cell values.
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This study aims to determine the variability of the components of fitness along the menstrual cycle (MC) of physically active eumenorrheic women. Fifteen subjects were monitored along two consecutive MCs through the calendar-based counting method in combination with a urine luteinizing hormone surge kit. Subjects were tested at the early follicular phase (EFP), pre-ovulatory or late follicular phase (LFP), and post-ovulatory or mid-luteal phase (MLP). In each session, the back squat one-repetition maximum (1-RM), maximum fat oxidation (MFO), maximum oxygen uptake (VO2max) and acute recovery capacity were determined. The results revealed a wide variability among components of fitness and a low to high variability among subjects (acute recovery: 3.6% [range 1.5 to 9.5%]; back squat 1-RM: 6.1% [range 2.2 to 11%]; VO2max: 6.6% [range 1.1 to 15%]; MFO: 23% [range 4.6 to 35%]). Despite the individual nature, considering the number and magnitude of the responses in each MC phase, VO2max and acute recovery capacity tended to be enhanced at the LFP, the MFO at the MLP, and the back squat 1-RM remained stable along the MC. Thus, practitioners are aware of which components are susceptible to change along the MC phase, but an individual monitoring is recommended.
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OBJECTIVES: To calculate the pooled diagnostic performances of whole-body [18F]FDG PET/MR in M staging of [18F]FDG-avid cancer entities. METHODS: A diagnostic meta-analysis was conducted on the [18F]FDG PET/MR in M staging, including studies: (1) evaluated [18F]FDG PET/MR in detecting distant metastasis; (2) compared[ 18F]FDG PET/MR with histopathology, follow-up, or asynchronous multimodality imaging as the reference standard; (3) provided data for the whole-body evaluation; (4) provided adequate data to calculate the meta-analytic performances. Pooled performances were calculated with their confidence interval. In addition, forest plots, SROC curves, and likelihood ratio scatterplots were drawn. All analyses were performed using STATA 16. RESULTS: From 52 eligible studies, 2289 patients and 2072 metastases were entered in the meta-analysis. The whole-body pooled sensitivities were 0.95 (95%CI: 0.91-0.97) and 0.97 (95%CI: 0.91-0.99) at the patient and lesion levels, respectively. The pooled specificities were 0.99 (95%CI: 0.97-1.00) and 0.97 (95%CI: 0.90-0.99), respectively. Additionally, subgroup analyses were performed. The calculated pooled sensitivities for lung, gastrointestinal, breast, and gynecological cancers were 0.90, 0.93, 1.00, and 0.97, respectively. The pooled specificities were 1.00, 0.98, 0.97, and 1.00, respectively. Furthermore, the pooled sensitivities for non-small cell lung, colorectal, and cervical cancers were 0.92, 0.96, and 0.86, respectively. The pooled specificities were 1.00, 0.95, and 1.00, respectively. CONCLUSION: [18F]FDG PET/MR was a highly accurate modality in M staging in the reported [18F]FDG-avid malignancies. The results showed high sensitivity and specificity in each reviewed malignancy type. Thus, our findings may help clinicians and patients to be confident about the performance of [18F]FDG PET/MR in the clinic. CLINICAL RELEVANCE STATEMENT: Although [18F]FDG PET/MR is not a routine imaging technique in current guidelines, mostly due to its availability and logistic issues, our findings might add to the limited evidence regarding its performance, showing a sensitivity of 0.95 and specificity of 0.97. KEY POINTS: ⢠The whole-body [18F]FDG PET/MR showed high accuracy in detecting distant metastases at both patient and lesion levels. ⢠The pooled sensitivities were 95% and 97% and pooled specificities were 99% and 97% at patient and lesion levels, respectively. ⢠The results suggested that 18F-FDG PET/MR was a strong modality in the exclusion and confirmation of distant metastases.
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Fluorodesoxiglucosa F18 , Neoplasias , Humanos , Radiofármacos , Sensibilidad y Especificidad , Imagen Multimodal/métodos , Estadificación de Neoplasias , Neoplasias/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodosRESUMEN
Chimeric antigen receptor (CAR) T-cell therapy is a cellular therapy in which the patient's T cells are enhanced to recognize and bind to specific tumor antigens. CAR T-cell therapy was initially developed for the treatment of leukemia, but its current main indication is the treatment of relapsed or refractory non-Hodgkin lymphoma. FDG PET/CT plays a fundamental role in the diagnosis, staging, therapy response assessment, and recurrence evaluation of patients with metabolically active lymphoma. Consistent with the examination's role in lymphoma management, FDG PET/CT is also the imaging modality of choice to evaluate patients before and after CAR T-cell therapy, and evidence supporting its utility in this setting continues to accumulate. In this article, we review current concepts in CAR T-cell therapy in patients with lymphoma, emphasizing the critical role of FDG PET/CT before and after therapy. A framework is presented that entails performing FDG PET/CT at four time points over the course of CAR T-cell therapy: pretherapy at baseline at the time of decision to administer CAR T-cell therapy and after any bridging therapies and posttherapy 1 and 3 months after infusion. PET parameters assessed at these time points predict various patient outcomes.
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Linfoma , Receptores Quiméricos de Antígenos , Humanos , Inmunoterapia Adoptiva/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Fluorodesoxiglucosa F18 , Linfoma/terapiaRESUMEN
To assess the impact of the COVID-19 pandemic on the diagnosis, staging and outcome of a selected population throughout the first two years of the pandemic, we evaluated oncology patients undergoing PET/CT at our institution. A retrospective population of lung cancer, melanoma, lymphoma and head and neck cancer patients staged using PET/CT during the first 6 months of the years 2019, 2020 and 2021 were included for analysis. The year in which the PET was performed was our exposure variable, and our two main outcomes were stage at the time of the PET/CT and overall survival (OS). A total of 1572 PET/CTs were performed for staging purposes during the first 6 months of 2019, 2020 and 2021. The median age was 66 (IQR 16), and 915 (58%) were males. The most prevalent staged cancer was lung cancer (643, 41%). The univariate analysis of staging at PET/CT and OS by year of PET/CT were not significantly different. The multivariate Cox regression of non-COVID-19 significantly different variables at univariate analysis and the year of PET/CT determined that lung cancer (HR 1.76 CI95 1.23-2.53, p < 0.05), stage III (HR 3.63 CI95 2.21-5.98, p < 0.05), stage IV (HR 11.06 CI95 7.04-17.36, p < 0.05) and age at diagnosis (HR 1.04 CI95 1.02-1.05, p < 0.05) had increased risks of death. We did not find significantly higher stages or reduced OS when assessing the year PET/CT was performed. Furthermore, OS was not significantly modified by the year patients were staged, even when controlled for non-COVID-19 significant variables (age, type of cancer, stage and gender).
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[This corrects the article DOI: 10.3389/fmed.2022.1051309.].
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ABSTRACT: We present a case of an 84-year-old man with a history of smoking, hypertension, and coronary artery disease with an incidental spiculated left apical pulmonary nodule, suspicious for a stage I non-small cell lung cancer. 18 F-FDG PET/CT performed for staging, which confirmed a small metabolically active pulmonary nodule. As an incidental finding, there was focal FDG uptake in the proximal descending aorta corresponding to a partially thrombosed outpouching of the aortic wall, in keeping with a penetrating atherosclerotic ulcer.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Úlcera Aterosclerótica Penetrante , Masculino , Humanos , Anciano de 80 o más Años , Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones , RadiofármacosRESUMEN
PURPOSE: To compare the diagnostic performance of multiparametric (mp) MRI to 18F-DCFPyL PET/MRI for detecting clinically significant (cs) prostate cancer (PCa) in men with low-/intermediate-risk PCa being considered for focal ablative therapy (FT), using 2 interpretation schemes, and to assess the rate of exclusion from FT for each modality. METHODS: This prospective study evaluated men with low- or intermediate-risk PCa, potential candidates for FT based on initial biopsy as per institutional protocol, who underwent 18F-DCFPyL PET/MRI. Each modality (mpMRI, PET/MRI using PROMISE classification [PET/MRI PROMISE], and PET/MRI considering any focal lesion on PET as positive [PETFL/MRI]) was assessed independently. All suspicious lesions underwent PET/MRI-ultrasound fusion biopsies. Diagnostic performances were calculated and compared using the exact binomial test on paired proportions. RESULTS: Thirty-four men (median age, 64 years; interquartile range, 60-70 years) were included. Overall, 40 of 67 lesions (60%) identified on mpMRI and/or PET/MRI were malignant, and 34 of 40 lesions (85%) were csPCa (≥6 mm ISUP [International Society of Urological Pathology Grade Group] GG1 or ISUP-GG ≥2). On lesion-level analysis, for detecting csPCa, sensitivity appeared higher for PETFL/MRI than mpMRI and PET/MRI PROMISE (97% vs 76% and 79%, respectively [P = 0.02 and 0.03]), whereas specificity was lower (30% vs 85% and 88%, respectively [P < 0.001]). The calculated overall accuracy rates for PETFL/MRI, mpMRI, and PET/MRI PROMISE were 64%, 81%, and 84%, respectively. PETFL/MRI, mpMRI, and PET/MRI PROMISE excluded 10 of 34 (29%), 7 of 34 (21%), and 6 of 34 (18%) men from FT, respectively. CONCLUSIONS: 18F-DCFPyL PET/MRI excluded nearly 30% of patients with low-/intermediate-risk PCa from FT, with a potential role in decreasing selection failure. Compared with mpMRI, PET/MRI had a higher sensitivity for detecting csPCa in men who were candidates for FT.ClinicalTrials.gov identifier NCT03149861.
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Imagen por Resonancia Magnética , Neoplasias de la Próstata , Masculino , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/cirugía , Biopsia Guiada por Imagen , Tomografía de Emisión de PositronesRESUMEN
BACKGROUND: In pediatrics, developing new pharmaceutical forms that offer safety and efficacy is crucial to improve pediatric pharmaceutical care. Orodispersible tablets do not require swallowing because orodispersible tablets dissolve quickly in the mouth, reducing the risk of choking and making medication administration safer and more straightforward. There is no solid dosage form in the pharmaceutical market offering a unit dose of Levothyroxine for pediatric hypothyroidism patients. OBJECTIVE: The objective of this study is to design and develop Orodispersible mini tablets of Levothyroxine Sodium (LT4 ODMTs) for pediatric doses. METHODS: LT4 ODMTs were prepared by direct compression with 10 and 15 µg, respectively, using StarLac® and Disolcel® as excipients. United States Pharmacopeia (USP-43) guidelines evaluated and determined pre-compression properties and quality control parameters. RESULTS: The LT4 ODMTs met the specified limits for quality controls. The Drug Content Uniformity was 97%, Hardness was less than 2.5 N, Friability was less than 0.3%, Disintegration time was less than 25 s, and dissolution profiles (Q 80% > 45 s) followed the USP requirements. Additionally, stability and microbiology assays were realized. CONCLUSION: These formulations are optimal for developing new LT4 ODMTs suitable for treating pediatric hypothyroidism.
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OBJECTIVE: To compare the preimplantation genetic testing for aneuploidy (PGT-A) results using the three most frequent criteria employed by preimplantation genetic laboratories and evaluate its impact on the number of euploid embryos available for transfer. METHODS: Retrospective and descriptive study including patients who underwent PGT-A between January 2018 and December 2020. Five hundred and nine PGT-A cycles and 2,079 blastocysts were analyzed by next-generation sequencing (NGS). We re-assigned the diagnosis of all blastocysts using three different criteria: strict (mosaicism thresholds from 20% to 80%), standard (from 30% to 70%) and excluding (mosaicism is not reported). We compared the euploid, aneuploid and mosaic embryos obtained in each criteria used. RESULTS: We observed PGT-A results discrepancies in 32.5% (165/509) of the cycles when the three different criteria were applied. The standard and excluding criteria showed 92 more euploid embryos (875/2,079) compared to the strict criteria (783/2,079). Evaluating the PGT-A results per cycle with the strict, standard and excluding criteria, the euploidy rates were 34.0%, 38.4% and 38.4% (p<0.001); aneuploidy rates were 59.0%, 55.8% and 61.6% (p<0.001) and mosaic rates were 7.0% and 5.8% (p<0.047), respectively. The mean number of euploid blastocysts available for transfer was 1.54±1.67 with the strict criteria, while the possibility to obtain an euploid embryo was higher if the standard or the excluding criteria were used 1.72±1.78 (p<0.001). CONCLUSIONS: This study highlights the importance of standardizing the criteria used for the interpretation of PGT-A blastocysts. We observed significant differences on PGT-A results associated solely to the criteria used.
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Diagnóstico Preimplantación , Embarazo , Femenino , Humanos , Diagnóstico Preimplantación/métodos , Estudios Retrospectivos , Pruebas Genéticas/métodos , Blastocisto , Aneuploidia , Secuenciación de Nucleótidos de Alto Rendimiento/métodosRESUMEN
The COVID-19 pandemic evolves constantly, requiring adaptable solutions to combat emerging SARS-CoV-2 variants. To address this, we created a pentameric scaffold based on a mammalian protein, which can be customized with up to 10 protein binding modules. This molecular scaffold spans roughly 20 nm and can simultaneously neutralize SARS-CoV-2 Spike proteins from one or multiple viral particles. Using only two different modules targeting the Spike's RBD domain, this construct outcompetes human antibodies from vaccinated individuals' serum and blocks in vitro cell attachment and pseudotyped virus entry. Additionally, the multibodies inhibit viral replication at low picomolar concentrations, regardless of the variant. This customizable multibody can be easily produced in procaryote systems, providing a new avenue for therapeutic development and detection devices, and contributing to preparedness against rapidly evolving pathogens.
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COVID-19 , SARS-CoV-2 , Animales , Humanos , Pandemias , Uniones Célula-Matriz , MamíferosRESUMEN
PURPOSE: To provide comprehensive data on the diagnostic and prognostic value of [18F]-FDG PET (PET) in anal canal cancer patients. METHODS: This study was designed following the PRISMA-DTA guidelines. For the meta-analysis, published original articles (until December 2022) that met the following criteria were included: Evaluated PET for locoregional and/or distant disease detection in patients with histopathology-proven anal canal cancer; Compared PET with a valid reference standard; Provided crude data to calculate meta-analytic estimates. Diagnostic measurements from subgroups were calculated in evaluating primary tumour detection, T stage, lymph node and distant metastases. Articles providing prognostic information on PET were also reported as a systematic review. For pooled meta-analytic calculations, the hierarchical method was used. The bivariate model was conducted to find the summary estimates. Analyses were performed using STATA 16. RESULTS: After the screening, 28 studies were eligible to enter the meta-analytic calculations, and data from 15 were reported descriptively. For distinguishing T3/T4 from other T-stages, PET had pooled sensitivity and specificity of 91%(95%CI:72%-97%) and 96%(95%CI:88%-98%), respectively. The sensitivity and specificity for detecting metastatic (regional and/or distant) disease were 100% (95%CI:82%-100%) and 95% (95%CI:90%-98%), respectively. For therapy response assessment, the sensitivity and specificity of PET were 96%(95%CI:78%-99%) and 86%(95%CI:75%-93%), respectively. Higher pre-treatment total metabolic tumour volume was predictive of poorer survival. Conversely, for those achieving complete metabolic response, the 2-year PFS was 94%(95%CI:91%-97%) versus 51%(95%CI:42%-59%) for others (p-value < 0.001). CONCLUSION: PET may be a useful tool for anal canal cancer therapy planning and provides valuable prognostic information.
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Fluorodesoxiglucosa F18 , Neoplasias , Humanos , Tomografía de Emisión de Positrones/métodos , Canal Anal , Radiofármacos , Sensibilidad y Especificidad , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodosRESUMEN
The broad adoption of transgenic crops has revolutionized agriculture. However, resistance to insecticidal proteins by agricultural pests poses a continuous challenge to maintaining crop productivity and new proteins are urgently needed to replace those utilized for existing transgenic traits. We identified an insecticidal membrane attack complex/perforin (MACPF) protein, Mpf2Ba1, with strong activity against the devastating coleopteran pest western corn rootworm (WCR) and a novel site of action. Using an integrative structural biology approach, we determined monomeric, pre-pore and pore structures, revealing changes between structural states at high resolution. We discovered an assembly inhibition mechanism, a molecular switch that activates pre-pore oligomerization upon gut fluid incubation and solved the highest resolution MACPF pore structure to-date. Our findings demonstrate not only the utility of Mpf2Ba1 in the development of biotechnology solutions for protecting maize from WCR to promote food security, but also uncover previously unknown mechanistic principles of bacterial MACPF assembly.
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Escarabajos , Insecticidas , Animales , Insecticidas/farmacología , Insecticidas/metabolismo , Zea mays/metabolismo , Escarabajos/fisiología , Control Biológico de Vectores , Plantas Modificadas Genéticamente/metabolismo , Animales Modificados Genéticamente , Perforina/metabolismo , Endotoxinas/metabolismo , Larva/metabolismo , Resistencia a los InsecticidasRESUMEN
PURPOSE: The aim of the study is to evaluate the prognostic value of a joint evaluation of PET and CT radiomics combined with standard clinical parameters in patients with HL. METHODS: Overall, 88 patients (42 female and 46 male) with a median age of 43.3 (range 21-85 years) were included. Textural analysis of the PET/CT images was performed using freely available software (LIFE X). 65 radiomic features (RF) were evaluated. Univariate and multivariate models were used to determine the value of clinical characteristics and FDG PET/CT radiomics in outcome prediction. In addition, a binary logistic regression model was used to determine potential predictors for radiotherapy treatment and odds ratios (OR), with 95% confidence intervals (CI) reported. Features relevant to survival outcomes were assessed using Cox proportional hazards to calculate hazard ratios with 95% CI. RESULTS: albumin (p = 0.034) + ALP (p = 0.028) + CT radiomic feature GLRLM GLNU mean (p = 0.012) (Area under the curve (AUC): 95% CI (86.9; 100.0)-Brier score: 3.9, 95% CI (0.1; 7.8) remained significant independent predictors for PFS outcome. PET-SHAPE Sphericity (p = 0.033); CT grey-level zone length matrix with high gray-level zone emphasis (GLZLM SZHGE mean (p = 0.028)); PARAMS XSpatial Resampling (p = 0.0091) as well as hemoglobin results (p = 0.016) remained as independent factors in the final model for a binary outcome as predictors of the need for radiotherapy (AUC = 0.79). CONCLUSION: We evaluated the value of baseline clinical parameters as well as combined PET and CT radiomics in HL patients for survival and the prediction of the need for radiotherapy treatment. We found that different combinations of all three factors/features were independently predictive of the here evaluated endpoints.
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Lung cancer remains the leading cancer-related death across North America. Imaging is fundamental. Recently, healthcare disparities came into research focus. Our aim was to explore disparity from an imaging, genetic, and outcome perspective. We utilized the AACR Project GENIE Biopharma Consortium (BPC) dataset v 1.1 to build a collated NSCLC dataset. Descriptive and analytical statistics were applied according to data characteristics. From 1849 patients, mean age was 64.4 y (±10.5), 58% (n = 1065) were female, 23% (n = 419) never smoked, 84% (n = 1545) were of white race, and 57% (n = 1052) were < stage III. No difference (p > 0.05) was found for baseline imaging by race. White race showed higher 3-month surveillance imaging (p = 0.048) and a baseline stage < IV (OR 0.61). KRAS (33.3 vs. 17.9%), STK11 (14.8 vs. 7.3%), and KEAP1 (13.3 vs. 5.3%) mutations were predominant among white patients while EGFR mutation (19.2 vs. 44.1%) was less predominant. Mutations in TP53 or KEAP1 had worse PFS and OS. The latter was also reduced in STK11, KRAS + STK11, and KRAS + KEAP1 mutations. Meanwhile, EGFR mutation had increased OS. Multivariate analysis showed that progression on imaging at 3 or 6 months (HR 1.69 and 1.43, respectively), TP53 (HR 1.37) and KRAS (HR 1.26) had lower OS while EGFR and LRP1B (HR 0.69 and 0.39, respectively) had higher OS. No racial disparity at baseline imaging was observed. Higher initial stages among non-white patients might reflect inequalities in accessing healthcare. However, race wasn't associated to OS. Finally, progression in imaging at 3 or 6 months showed the higher hazard ratios for death.