Diagnostic performance of whole-body [18F]FDG PET/MR in cancer M staging: A systematic review and meta-analysis.

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.

Role of FDG PET/CT in Patients With Lymphoma Treated With Chimeric Antigen Receptor T-Cell Therapy: Current Concepts.

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.

The Variability of the Components of Fitness along the Menstrual Cycle.

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.

18F-FDG PET/MRI in Detection of Pulmonary Malignancies: A Systematic Review and Meta-Analysis.

Background There have been conflicting results regarding fluorine 18-labeled fluorodeoxyglucose (18F-FDG) PET/MRI diagnostic performance in lung malignant neoplasms. Purpose To evaluate the diagnostic performance of 18F-FDG PET/MRI for the detection of pulmonary malignant neoplasms. Materials and Methods A systematic search was conducted within the Scopus, Web of Science, and PubMed databases until December 31, 2021. Published original articles that met the following criteria were considered eligible for meta-analysis: (a) detecting malignant lesions in the lung, (b) comparing 18F-FDG PET/MRI with a valid reference standard, and (c) providing data for the meta-analytic calculations. A hierarchical method was used to pool the performances. The bivariate model was used to find the summary points and 95% CIs. The hierarchical summary receiver operating characteristic model was used to draw the summary receiver operating characteristic curve and calculate the area under the curve. The Higgins I2 statistic and Cochran Q test were used for heterogeneity assessment. Results A total of 43 studies involving 1278 patients met the inclusion criteria and were included in the meta-analysis. 18F-FDG PET/MRI had a pooled sensitivity and specificity of 96% (95% CI: 84, 99) and 100% (95% CI: 98, 100), respectively. 18F-FDG PET/CT had a pooled sensitivity and specificity of 99% (95% CI: 61, 100) and 99% (95% CI: 94, 100), respectively, which were comparable with those of 18F-FDG PET/MRI. At meta-regression, studies in which contrast media (P = .03) and diffusion-weighted imaging (P = .04) were used as a part of a pulmonary 18F-FDG PET/MRI protocol showed significantly higher sensitivities. Conclusion Fluorine 18-labeled fluorodeoxyglucose (18F-FDG) PET/MRI was found to be accurate and comparable with 18F-FDG PET/CT in the detection of malignant pulmonary lesions, with significantly improved sensitivity when advanced acquisition protocols were used. © RSNA, 2023 Supplemental material is available for this article.

Associations of fertility parameters with fatty acids and DNA methylation in Mexican women undergoing in vitro fertilization.

BACKGROUND: Fatty acids (FA) likely affect human fertility at multiple levels, as deviations from physiological FA profiles are obesogenic, and FA can modify DNA methylation (DNAm). Yet, the interplay of follicular fluid (FF) and serum FA with BMI and percentage body fat (PBF) in human fertility is not completely understood. Also, associations of DNAm with fertility are largely unexplored. METHODS: Reproductive parameters ranging from retrieved oocyte number to infant birth weight, were recorded in Mexican women undergoing in vitro fertilization (n = 88). Multiple regression analysis sought BMI-adjusted and age-adjusted associations. Receiver operating characteristic analysis tested for discrimination between outcomes. RESULTS: Associations of FF and serum FA were markedly distinct. While various FF FA (C16:1, C18:0, C20:2, C20:3, arachidonic acid) were significantly and inversely associated only with retrieved oocyte number, selected serum FA were associated with a broad range of pre-fertilization and post-fertilization parameters. Associations of BMI and FF FA were complex, as arachidonic acid was inversely associated with both BMI and retrieved oocyte number, while oleic acid (OA) was directly associated with BMI and PBF. Ultrasound-assessed clinical pregnancy outcome (CP) was directly associated with serum OA but inversely with its trans isomer elaidic acid (EA) and with BMI. Compounded BMI, serum EA and OA discriminated CP well (AUC = 0.74). Whole blood DNA methylation was significantly associated with and a moderate predictor (AUC = 0.66) of percent fertilized oocytes. CONCLUSIONS: Overall FF FA pool composition rather than FA identity may impact oocyte production and cellular memory of FF FA is lost as the oocyte exits the follicular environment. The contrasting associations of BMI, FF OA and arachidonic acid suggest that the control of oocyte homeostasis by FF FA is uncoupled from BMI. Further studies are warranted to assess the potential of compounding BMI with serum EA and OA to predict CP.

[18F]-FDG PET in anal canal cancer: a systematic review and meta-analysis.

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.

The role of [18F]-DCFPyL PET/MRI radiomics for pathological grade group prediction in prostate cancer.

PURPOSE: To evaluate the diagnostic accuracy of [18F]-DCFPyL PET/MRI radiomics for the prediction of pathological grade group in prostate cancer (PCa) in therapy-naïve patients. METHODS: Patients with confirmed or suspected PCa, who underwent [18F]-DCFPyL PET/MRI (n = 105), were included in this retrospective analysis of two prospective clinical trials. Radiomic features were extracted from the segmented volumes following the image biomarker standardization initiative (IBSI) guidelines. Histopathology obtained from systematic and targeted biopsies of the PET/MRI-detected lesions was the reference standard. Histopathology patterns were dichotomized as ISUP GG 1-2 vs. ISUP GG ≥ 3 categories. Different single-modality models were defined for feature extraction, including PET- and MRI-derived radiomic features. The clinical model included age, PSA, and lesions' PROMISE classification. Single models, as well as different combinations of them, were generated to calculate their performances. A cross-validation approach was used to evaluate the internal validity of the models. RESULTS: All radiomic models outperformed the clinical models. The best model for grade group prediction was the combination of PET + ADC + T2w radiomic features, showing sensitivity, specificity, accuracy, and AUC of 0.85, 0.83, 0.84, and 0.85, respectively. The MRI-derived (ADC + T2w) features showed sensitivity, specificity, accuracy, and AUC of 0.88, 0.78, 0.83, and 0.84, respectively. PET-derived features showed 0.83, 0.68, 0.76, and 0.79, respectively. The baseline clinical model showed 0.73, 0.44, 0.60, and 0.58, respectively. The addition of the clinical model to the best radiomic model did not improve the diagnostic performance. The performances of MRI and PET/MRI radiomic models as per the cross-validation scheme yielded an accuracy of 0.80 (AUC = 0.79), whereas clinical models presented an accuracy of 0.60 (AUC = 0.60). CONCLUSION: The combined [18F]-DCFPyL PET/MRI radiomic model was the best-performing model and outperformed the clinical model for pathological grade group prediction, indicating a complementary value of the hybrid PET/MRI model for non-invasive risk stratification of PCa. Further prospective studies are required to confirm the reproducibility and clinical utility of this approach.

Analysis of Bacterial Microbiota of Aerated Compost Teas and Effect on Tomato Growth.

Mature composts and their water-based extracts, known as aerated compost teas (ACTs), are biofertilizers that share bioactive effects like soil restoration and plant health promotion, widely used for sustainable agriculture. Bioactive effects of compost and ACTs could be associated with their physicochemical and biological characteristics, like carbon/nitrogen (C/N) ratio and microbiota structure respectively. In our study, we elaborated ACTs using mature homemade compost, wheat bran, and grass clippings, following the C/N ratio criteria. Irrigation of tomato plantlets with ACT whose C/N ratio was close to the expected C/N ratio for mature compost evidenced plant growth promotion. Exploring the bacterial microbiota of elaborated ACTs and origin compost revealed significant structural differences, including phyla involved in N mineralization and free-living N-fixing bacteria. Therefore, ACTs harbor diverse bacterial microbiota involved in the N cycle, which would enrich plant and soil bacterial communities at the taxonomic and functional levels. Furthermore, ACTs are considered a part of agroecological and circular economy approaches.

Impact of 18F-DCFPyL PET on Staging and Treatment of Unfavorable Intermediate or High-Risk Prostate Cancer.

Background Data regarding 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine 3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL) PET in primary staging of prostate cancer (PCa) are limited. Purpose To compare the performance of 18F-DCFPyL PET/CT or PET/MRI (PET) with bone scan and CT with or without multiparametric MRI (hereafter, referred to as conventional imaging) in the initial staging of men with unfavorable intermediate or high-risk PCa and to assess treatment change after PET. Materials and Methods This prospective study evaluated men with biopsy-proven, untreated, unfavorable intermediate or high-risk PCa with 0 to four metastases or equivocal for extensive metastases (more than four) who underwent PET between May 2018 and December 2020. The diagnostic performance of PET in detecting pelvic nodal and distant metastases was compared with conventional imaging alone. Metastatic sites at conventional imaging and PET were compared with a composite reference standard including histopathologic analysis, correlative imaging, and/or clinical and biochemical follow-up. The intended treatment before PET was compared with the treatment plan established after performing PET. Detection rate, sensitivity, and specificity of conventional imaging and PET were compared by using McNemar exact test on paired proportions. Results The study consisted of 108 men (median age, 66 years; IQR, 61-73 years) with no metastases (n = 84), with oligometastases (four or fewer metastases; 22 men), or with equivocal findings for extensive metastases (n = 2). Detection rates at PET and conventional imaging for nodal metastases were 34% (37 of 108) and 11% (12 of 108) (P < .001), respectively, and those for distant metastases were 22% (24 of 108) and 10% (11 of 108) (P = .02), respectively. PET altered stage in 43 of 108 (40%) and treatment in 24 of 108 (22%) men. The most frequent treatment change was from systemic to local-regional therapy in 10 of 108 (9%) and from local-regional to systemic therapy in nine of 108 (8%) men. Equivocal findings were encountered less frequently with PET (one of 108; 1%) than with conventional imaging (29 of 108; 27%). Conclusion Initial staging with 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine 3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL) PET after conventional imaging (bone scan and CT with or without multiparametric MRI) helped to detect more nodal and distant metastases than conventional imaging alone and changed treatment in 22% of men. Clinical trial registration no. NCT03535831, NCT03718260 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Jadvar in this issue.

Diagnostic performance of [18F]-FDG PET/MR in evaluating colorectal cancer: a systematic review and meta-analysis.

PURPOSE: To calculate the diagnostic performance of [18F]-FDG PET/MR in colorectal cancer (CRC). METHODS: This study was designed following the PRISMA-DTA guidelines. To be included, published original articles (until December 31, 2021) that met the following criteria were considered eligible: (1) evaluated [18F]-FDG PET/MR as the diagnostic method to detect CRC; (2) compared [18F]-FDG PET/MR with histopathology as the reference standard, or clinical/imaging composite follow-up when pathology was not available; (3) provided adequate crude data for meta-analysis. The diagnostic pooled measurements were calculated at patient and lesion levels. Regarding sub-group analysis, diagnostic measurements were calculated in "TNM staging," "T staging," "N staging," "M staging," and "liver metastasis" sub-groups. Additionally, we calculated the pooled performances in "rectal cancer: patient-level" and "rectal cancer: lesion-level" sub-groups. A hierarchical method was used to pool the performances. The bivariate model was conducted to find the summary points. Analyses were performed using STATA 16. RESULTS: A total of 1534 patients from 18 studies were entered. The pooled sensitivities in CRC lesion detection (tumor, lymph nodes, and metastases) were 0.94 (95%CI: 0.89-0.97) and 0.93 (95%CI: 0.82-0.98) at patient-level and lesion-level, respectively. The pooled specificities were 0.89 (95%CI: 0.84-0.93) and 0.95 (95%CI: 0.90-0.98) at patient-level and lesion-level, respectively. In sub-groups, the highest sensitivity (0.97, 95%CI: 0.86-0.99) and specificity (0.99, 95%CI: 0.84-1.00) were calculated for "M staging" and "rectal cancer: lesion-level," respectively. The lowest sensitivity (0.81, 95%CI: 0.65-0.91) and specificity (0.79, 95%CI: 0.52-0.93) were calculated for "N staging" and "T staging," respectively. CONCLUSION: This meta-analysis showed an overall high diagnostic performance for [18F]-FDG PET/MR in detecting CRC lesions/metastases. Thus, this modality can play a significant role in several clinical scenarios in CRC staging and restaging. Specifically, one of the main strengths of this modality is ruling out the existence of CRC lesions/metastases. Finally, the overall diagnostic performance was not found to be affected in the post-treatment setting.

Influence of sarcopenia, clinical data, and 2-[18F] FDG PET/CT in outcome prediction of patients with early-stage adenocarcinoma esophageal cancer.

PURPOSE: To determine the prognostic value of sarcopenia measurements done on staging 2-[18F] FDG PET/CT together with metabolic activity of the tumor in patients with adenocarcinoma esophagogastric cancer with surgical treatment. METHODS: Patients with early-stage, surgically treated esophageal adenocarcinoma and available pre-treatment 2-[18F] FDG PET/CT were included. The standard uptake value (SUV) and SUV normalized by lean body mass (SUL) were recorded. Skeletal muscle index (SMI) was measured at the L3 level on the CT component of the PET/CT. Sarcopenia was defined as SMI < 34.4cm2/m2 in women and < 45.4cm2/m2 in men. RESULTS: Of the included 145 patients. 30% were sarcopenic at baseline. On the univariable Cox proportional hazards analysis, ECOG, surgical T and N staging, lymphovascular invasion (LVI) positive lymph nodes, and sarcopenia were significant prognostic factors concerning RFS and OS. On multivariable Cox regression analysis, surgical N staging (p = 0.025) and sarcopenia (p = 0.022) remained significant poor prognostic factors for OS and RFS. Combining the clinical parameters with the imaging-derived nutritional evaluation of the patient but not metabolic parameters of the tumor showed improved predictive ability for OS and RFS. CONCLUSION: Combining the patients' imaging-derived sarcopenic status with standard clinical data, but not metabolic parameters, offered an overall improved prognostic value concerning OS and RFS.

Somatic hypermutation profiles in stereotyped IGHV4-34 receptors from South American chronic lymphocytic leukemia patients.

Chronic lymphocytic leukemia (CLL) is the most common mature B-cell neoplasm in the West. IGHV4-34 is one of the most frequently used genes in CLL patients, which usually display an indolent outcome. In this study, we explored the mutational profile of CLL patients expressing IGHV4-34 within different stereotypes and their association with prognostic factors and clinical outcome. A multi-institutional cohort of unselected 1444 CLL patients was analyzed by RT-PCR and bidirectional sequencing. Cytogenetics and molecular cytogenetics analyses were also performed. We identified 144 (10%) IGHV4-34 expressing cases, 119 mutated (M), 44 of them with stereotyped B-cell receptors. Subset #4 was the most frequent (56.8% of cases) followed by subsets #16 (13.6%), #29 (6.8%), and #201 (2.3%), with different distribution among countries. Analysis of somatic hypermutation profile showed significant differences among stereotyped subsets for G28>D/E, P45>S, E55>Q, and S64>I changes (p < 0.01) and high frequency of disruption of the glycosylation motif in the VH CDR2 region. All stereotyped IGHV4-34 cases showed normal karyotypes. Deletion 13q14 as a sole alteration was present in 42.8% of stereotyped cases with a different distribution among subsets. A shorter time to first treatment was found in non-stereotyped vs. stereotyped M-IGHV4-34 patients (p = 0.034). Our results add new information supporting the importance of recurrent amino acid changes at particular positions, contributing to refine the molecular characterization of South American CLL patients.

Production, purification and characterization of a double-tagged TEV protease.

Many recombinant proteins are products of great value in biomedical and industrial fields. The use of solubility and affinity tags are commonly used to increase yields and facilitate the purification process. However, it is of paramount importance in several applications to remove the fusion tag from the final product. In this regard, the Tobacco Etch Virus protease (TEV) is one of the most widely used for tag removal. The presence in the TEV of the same tag to be removed facilitates the separation of TEV and the tag from the cleaved recombinant protein in a single purification step. We generated a double-tagged (StrepTagII and HisTag) TEV variant with reported mutations that improve the activity, the expression yield in E.coli, and that decrease the auto-proteolysis. This TEV can be easily purified by two consecutive affinity chromatography steps with high yields and purity. The cleavage reaction can be done to almost completeness in as fast as 15 min at room temperature and the removal of the protease and tags is performed in a single purification step, independent of the previous presence of a StrepTagII or a HisTag on the target.

Deep learning for whole-body medical image generation.

BACKGROUND: Artificial intelligence (AI) algorithms based on deep convolutional networks have demonstrated remarkable success for image transformation tasks. State-of-the-art results have been achieved by generative adversarial networks (GANs) and training approaches which do not require paired data. Recently, these techniques have been applied in the medical field for cross-domain image translation. PURPOSE: This study investigated deep learning transformation in medical imaging. It was motivated to identify generalizable methods which would satisfy the simultaneous requirements of quality and anatomical accuracy across the entire human body. Specifically, whole-body MR patient data acquired on a PET/MR system were used to generate synthetic CT image volumes. The capacity of these synthetic CT data for use in PET attenuation correction (AC) was evaluated and compared to current MR-based attenuation correction (MR-AC) methods, which typically use multiphase Dixon sequences to segment various tissue types. MATERIALS AND METHODS: This work aimed to investigate the technical performance of a GAN system for general MR-to-CT volumetric transformation and to evaluate the performance of the generated images for PET AC. A dataset comprising matched, same-day PET/MR and PET/CT patient scans was used for validation. RESULTS: A combination of training techniques was used to produce synthetic images which were of high-quality and anatomically accurate. Higher correlation was found between the values of mu maps calculated directly from CT data and those derived from the synthetic CT images than those from the default segmented Dixon approach. Over the entire body, the total amounts of reconstructed PET activities were similar between the two MR-AC methods, but the synthetic CT method yielded higher accuracy for quantifying the tracer uptake in specific regions. CONCLUSION: The findings reported here demonstrate the feasibility of this technique and its potential to improve certain aspects of attenuation correction for PET/MR systems. Moreover, this work may have larger implications for establishing generalized methods for inter-modality, whole-body transformation in medical imaging. Unsupervised deep learning techniques can produce high-quality synthetic images, but additional constraints may be needed to maintain medical integrity in the generated data.

Detection of clinically significant prostate cancer with 18F-DCFPyL PET/multiparametric MR.

PURPOSE: To assess whether 18F-DCFPyL PET/multiparametric (mp)MR contributes to the diagnosis of clinically significant (cs) prostate cancer (PCa) compared to mpMR in patients with suspicion of PCa, or patients being considered for focal ablative therapies (FT). PATIENTS AND METHODS: This ethics review board-approved, prospective study included 55 men with suspicion of PCa and negative systematic biopsies or clinically discordant low-risk PCa (n = 21) or those being considered for FT (n = 34) who received 18F-DCFPyL PET/mpMR. Each modality, PET, mpMR, and PET/MR (using the PROMISE classification), was assessed independently. All suspicious lesions underwent PET/MR-ultrasound fusion biopsies. RESULTS: There were 45/55 patients (81.8%) that had histologically proven PCa and 41/55 (74.5%) were diagnosed with csPCa. Overall, 61/114 lesions (53.5%) identified on any modality were malignant; 49/61 lesions (80.3%) were csPCa. On lesion-level analysis, for detection of csPCa, the sensitivity of PET was higher than that of mpMR and PET/MR (86% vs 67% and 69% [p = 0.027 and 0.041, respectively]), but at a lower specificity (32% vs 85% and 86%, respectively [p < 0.001]). The performance of MR and PET/MR was comparable. For identification of csPCa in PI-RADS ≥ 3 lesions, the AUC (95% CI) for PET, mpMR, and PET/MR was 0.75 (0.65-0.86), 0.69 (0.56-0.82), and 0.78 (0.67-0.89), respectively. The AUC for PET/MR was significantly larger than that of mpMR (p = 0.04). CONCLUSION: PSMA PET detects more csPCa than mpMR, but at low specificity. The performance PET/MR is better than mpMR for detection of csPCa in PI-RADS ≥ 3 lesions. CLINICAL REGISTRATION: NCT03149861.

Coordinated binding of a two-component insecticidal protein from Alcaligenes faecalis to western corn rootworm midgut tissue.

AfIP-1A/1B is a two-component insecticidal protein identified from the soil bacterium Alcaligenes faecalis that has high activity against western corn rootworm (WCR; Diabrotica virgifera virgifera LeConte). Previous results revealed that AfIP-1A/1B is cross-resistant to the binary protein from Bacillus thuringiensis (Bt), Cry34Ab1/Cry35Ab1 (also known as Gpp34Ab1/Tpp35Ab1; Crickmore et al., 2020), which was attributed to shared binding sites in WCR gut tissue (Yalpani et al., 2017). To better understand the interaction of AfIP-1A/1B with its receptor, we have systematically evaluated the binding of these proteins with WCR brush border membrane vesicles (BBMVs). Our findings show that AfIP-1A binds directly to BBMVs, while AfIP-1B does not; AfIP-1B binding only occurred in the presence of AfIP-1A which was accompanied by the presence of stable, high molecular weight oligomers of AfIP-1B observed on denaturing protein gels. Additionally, we show that AfIP-1A/1B forms pores in artificial lipid membranes. Finally, binding of AfIP-1A/1B was found to be reduced in BBMVs from Cry34Ab1/Cry35Ab1-resistant WCR where Cry34Ab1/Cry35Ab1 binding was also reduced. The reduced binding of both proteins is consistent with recognition of a shared receptor that has been altered in the resistant strain. The coordination of AfIP-1B binding by AfIP-1A, the similar structures between AfIP-1A and Cry34Ab1, along with their shared binding sites and cross-resistance, suggest a similar role for AfIP1A and Cry34Ab1 in receptor recognition and docking site for their cognate partners, AfIP-1B and Cry35Ab1, respectively.

Banking sector performance during the COVID-19 crisis.

This paper examines the impact of financial sector policy announcements on bank stocks around the world during the onset of the COVID-19 crisis. Overall, we find that liquidity support, borrower assistance programs and monetary easing moderated the adverse impact from the crisis, but their impact varied considerably across banks and countries. By contrast, countercyclical prudential measures led to negative abnormal returns in bank stocks, suggesting that markets price the downside risks associated with these policies.

Oocyte maturation arrest produced by TUBB8 mutations: impact of genetic disorders in infertility treatment.

Oocyte maturation defect is a challenging situation in the management of infertility, the etiology may be related to endocrine causes, protocols used in ovarian stimulation, oocyte intrinsic defects or procedures in embryology laboratory. We report three Mexican females in treatment for primary infertility with non-mature oocytes after ovary stimulation and oocyte capture in whom a genetic diagnosis of TUBB8-oocyte maturation defect was revealed by exome sequencing. Two couples achieved pregnancies though oocyte donation after establishing the genetic etiology. Our results expand the role of TUBB8-disorders in patients of non-Asian ethnicity. Oocyte maturation defects of monogenic origin are a growing group of disorders that endocrinologists and reproductive medicine specialists should be aware in order to provide referral to genetics for establish a correct and opportune diagnosis.

A selective insecticidal protein from Pseudomonas mosselii for corn rootworm control.

The coleopteran insect western corn rootworm (WCR, Diabrotica virgifera virgifera) is an economically important pest in North America and Europe. Transgenic corn plants producing Bacillus thuringiensis (Bt) insecticidal proteins have been useful against this devastating pest, but evolution of resistance has reduced their efficacy. Here, we report the discovery of a novel insecticidal protein, PIP-47Aa, from an isolate of Pseudomonas mosselii. PIP-47Aa sequence shows no shared motifs, domains or signatures with other known proteins. Recombinant PIP-47Aa kills WCR, two other corn rootworm pests (Diabrotica barberi and Diabrotica undecimpunctata howardi) and two other beetle species (Diabrotica speciosa and Phyllotreta cruciferae), but it was not toxic to the spotted lady beetle (Coleomegilla maculata) or seven species of Lepidoptera and Hemiptera. Transgenic corn plants expressing PIP-47Aa show significant protection from root damage by WCR. PIP-47Aa kills a WCR strain resistant to mCry3A and does not share rootworm midgut binding sites with mCry3A or AfIP-1A/1B from Alcaligenes that acts like Cry34Ab1/Cry35Ab1. Our results indicate that PIP-47Aa is a novel insecticidal protein for controlling the corn rootworm pests.

[Combined Preimplantation Genetic Testing for Aneuploidy and Monogenic Disease in a Mexican Family Affected by X-linked Hypohidrotic Ectodermal Dysplasia].

Background: Hypohidrotic ectodermal dysplasia (HED) is a genetic skin condition presenting as hypohidrosis, hypodontia, and hypotrichosis, resulting in an important burden for affected families. The most common form of HED has an X-linked inheritance and female carriers have the option of prenatal or preimplantation genetic testing (PGT) to avoid transmission of the disease. A combined PGT for a mutation in EDA gene and aneuploidies in a Mexican carrier of X-linked HED is reported. Materials and Methods: Ovarian stimulation and assisted reproduction procedures were performed in a private academic medical center. PGT for a novel c.707-1G>A (rs886039466) mutation in EDA gene and chromosomal aneuploidies was performed by massive parallel and Sanger sequencing. Results: In the first PGT, the transfer of two blastocysts did not result in a pregnancy. An accumulative stimulation approach was decided to improve pregnancy chances for a second PGT procedure. Three ovarian stimulations were performed and 10 blastocysts coming from fresh and vitrified oocytes were genetically analyzed. A single embryo transfer produced a healthy non-carrier euploid girl. Discussion: PGT combining aneuploidy and mutation analyses is an alternative for female carriers of X-linked and other Mendelian disorders in Latin-American countries. In the era of genomic and personalized medicine, medically assisted reproduction techniques, such as PGT, are shifting from only infertility to preventive genetics.