Fetal growth restriction and placental defects in obese mice are associated with impaired decidualisation: the role of increased leptin signalling modulators SOCS3 and PTPN2.

Decidualisation of the endometrium is a key event in early pregnancy, which enables embryo implantation. Importantly, the molecular processes impairing decidualisation in obese mothers are yet to be characterised. We hypothesise that impaired decidualisation in obese mice is mediated by the upregulation of leptin modulators, the suppressor of cytokine signalling 3 (SOCS3) and the protein tyrosine phosphatase non-receptor type 2 (PTPN2), together with the disruption of progesterone (P4)-signal transducer and activator of transcription (STAT3) signalling. After feeding mice with chow diet (CD) or high-fat diet (HFD) for 16 weeks, we confirmed the downregulation of P4 and oestradiol (E2) steroid receptors in decidua from embryonic day (E) 6.5 and decreased proliferation of stromal cells from HFD. In vitro decidualised mouse endometrial stromal cells (MESCs) and E6.5 deciduas from the HFD showed decreased expression of decidualisation markers, followed by the upregulation of SOCS3 and PTPN2 and decreased phosphorylation of STAT3. In vivo and in vitro leptin treatment of mice and MESCs mimicked the results observed in the obese model. The downregulation of Socs3 and Ptpn2 after siRNA transfection of MESCs from HFD mice restored the expression level of decidualisation markers. Finally, DIO mice placentas from E18.5 showed decreased labyrinth development and vascularisation and fetal growth restricted embryos. The present study revealed major defects in decidualisation in obese mice, characterised by altered uterine response to E2 and P4 steroid signalling. Importantly, altered hormonal response was associated with increased expression of leptin signalling modulators SOCS3 and PTPN2. Elevated levels of SOCS3 and PTPN2 were shown to molecularly affect decidualisation in obese mice, potentially disrupting the STAT3-PR regulatory molecular hub.

Effectiveness and safety of a 1L polyethylene glycol and ascorbic acid preparation for colonoscopy in routine clinical practice in Spain.

BACKGROUND AND AIMS: Large clinical trials and small real-world studies show that a 1L polyethylene glycol and ascorbic acid solution (1L PEG-ASC) is an effective and safe bowel preparation for colonoscopy. Here, the effectiveness and safety of 1L PEG-ASC was evaluated in a large cohort of patients in routine clinical practice in Spain. METHODS: A sub-analysis was performed in an observational, multicenter, retrospective study assessing the effectiveness and safety of 1L PEG-ASC in adult patients undergoing a colonoscopy at 10 centers in Spain. Cleansing quality was assessed with the Boston Bowel Preparation Scale, scores ≥6 with all segmental scores ≥2 was considered adequate colon cleansing, high-quality was considered as cleansing ≥8 or =3 in the right colon. Polyp and adenoma detection rates, and adverse events were also assessed. RESULTS: Data was collected from 7160 patients: 48.3% males; mean age 58.0, 33.6% ≥65 years old. Adequate overall bowel cleansing was achieved in 95.6% of patients (95% CI 95.1%-96.0%), high quality cleansing in 74.4% (95% CI 73.4%-75.4%) and high-quality right colon cleansing in 66.0% (95% CI 64.9-67.1). The adequate overall cleansing rate was 97.0% with a split-dose and 94.0% with same-day regimen (P<0.0001), and high-quality right colon cleansing was 69.0% and 62.5% (P<0.0001), respectively. Colonoscopy was completed in 97.2% of cases. A multivariate regression analysis revealed that an overnight split-dose regimen and age <65 years were independent predictors of adequate bowel cleansing of the overall colon, age <65 years and female gender were independent predictors of HQ cleansing of the overall colon, and the three covariates were independent predictors of HQ cleansing of the right colon. At least one adverse event was experienced by 3.3% of participants, with nausea (1.5%) and vomiting (1.2%) being the most frequent. CONCLUSION: This sub-analysis confirmed 1L PEG-ASC to be an effective and safe bowel cleansing preparation in a real world setting in Spain.

A data-centric machine learning approach to improve prediction of glioma grades using low-imbalance TCGA data.

Accurate prediction and grading of gliomas play a crucial role in evaluating brain tumor progression, assessing overall prognosis, and treatment planning. In addition to neuroimaging techniques, identifying molecular biomarkers that can guide the diagnosis, prognosis and prediction of the response to therapy has aroused the interest of researchers in their use together with machine learning and deep learning models. Most of the research in this field has been model-centric, meaning it has been based on finding better performing algorithms. However, in practice, improving data quality can result in a better model. This study investigates a data-centric machine learning approach to determine their potential benefits in predicting glioma grades. We report six performance metrics to provide a complete picture of model performance. Experimental results indicate that standardization and oversizing the minority class increase the prediction performance of four popular machine learning models and two classifier ensembles applied on a low-imbalanced data set consisting of clinical factors and molecular biomarkers. The experiments also show that the two classifier ensembles significantly outperform three of the four standard prediction models. Furthermore, we conduct a comprehensive descriptive analysis of the glioma data set to identify relevant statistical characteristics and discover the most informative attributes using four feature ranking algorithms.

Thrombosis and infections associated with PICC in onco-hematological patients, what is their relevance?

PURPOSE: Peripherally inserted central venous catheters (PICC) in the onco-hematological patients may be associated with thrombosis or infections that may have short- to medium-term repercussions. MATERIAL AND METHODS: Single-centre retrospective analysis of a prospectively collected cohort. Primary objective was to establish the PICC-thrombosis and infections incidence. Secondary objectives were to analyze profile of patients suffering from these complications and variables associated with an increased likelihood of developing these events. RESULTS: 549 patients were recruited. 58.5% (n = 321) were oncology patients and 41.5% (n = 228) hematology patients. The incidence of PICC-associated thrombosis was 3.5% (n = 19). Thrombosis was associated with progression of the underlying malignant pathology in 10.6% (n = 2) of cases. No association was found between clinical variables analysed and development of thrombosis. Incidence of PICC-associated infections was 7.65% (n = 42). In the 30 days prior to PICC infection, 57.1% (n = 24) had a febrile syndrome of another focus, 73.8% (n = 11) had been hospitalized, 49.5% (n = 25) had a neutrophil count of 0-500 cells/mm3 and 47.6% (n = 20) had an episode of neutropenic fever. Variables significantly associated with the development of infection were hematological patients, high-flow PICC, 3-lm PICC or PICC insertion because of administration of vesicant therapy. CONCLUSIONS: Incidence of PICC-associated thrombosis is low and apparently less prognostically aggressive than other forms of thrombosis associated with cancer, without identify predictive factors. Infection was more prevalent and the identification of risk factors in our series could facilitate its prevention.

A proteomic approach supports the clinical relevance of TAT-Cx43266-283 in glioblastoma.

Glioblastoma (GBM) is the most frequent and aggressive primary brain cancer. The Src inhibitor, TAT-Cx43266-283, exerts antitumor effects in in vitro and in vivo models of GBM. Because addressing the mechanism of action is essential to translate these results to a clinical setting, in this study we carried out an unbiased proteomic approach. Data-independent acquisition mass spectrometry proteomics allowed the identification of 190 proteins whose abundance was modified by TAT-Cx43266-283. Our results were consistent with the inhibition of Src as the mechanism of action of TAT-Cx43266-283 and unveiled antitumor effectors, such as p120 catenin. Changes in the abundance of several proteins suggested that TAT-Cx43266-283 may also impact the brain microenvironment. Importantly, the proteins whose abundance was reduced by TAT-Cx43266-283 correlated with an improved GBM patient survival in clinical datasets and none of the proteins whose abundance was increased by TAT-Cx43266-283 correlated with shorter survival, supporting its use in clinical trials.

The GPI-anchor biosynthesis pathway is critical for syncytiotrophoblast differentiation and placental development.

The glycosylphosphatidylinositol (GPI) biosynthetic pathway in the endoplasmic reticulum (ER) is crucial for generating GPI-anchored proteins (GPI-APs), which are translocated to the cell surface and play a vital role in cell signaling and adhesion. This study focuses on two integral components of the GPI pathway, the PIGL and PIGF proteins, and their significance in trophoblast biology. We show that GPI pathway mutations impact on placental development impairing the differentiation of the syncytiotrophoblast (SynT), and especially the SynT-II layer, which is essential for the establishment of the definitive nutrient exchange area within the placental labyrinth. CRISPR/Cas9 knockout of Pigl and Pigf in mouse trophoblast stem cells (mTSCs) confirms the role of these GPI enzymes in syncytiotrophoblast differentiation. Mechanistically, impaired GPI-AP generation induces an excessive unfolded protein response (UPR) in the ER in mTSCs growing in stem cell conditions, akin to what is observed in human preeclampsia. Upon differentiation, the impairment of the GPI pathway hinders the induction of WNT signaling for early SynT-II development. Remarkably, the transcriptomic profile of Pigl- and Pigf-deficient cells separates human patient placental samples into preeclampsia and control groups, suggesting an involvement of Pigl and Pigf in establishing a preeclamptic gene signature. Our study unveils the pivotal role of GPI biosynthesis in early placentation and uncovers a new preeclampsia gene expression profile associated with mutations in the GPI biosynthesis pathway, providing novel molecular insights into placental development with implications for enhanced patient stratification and timely interventions.

Increased ER Stress and Unfolded Protein Response Activation in Epithelial and Inflammatory Cells in Hypersensitivity Pneumonitis.

Several types of cytotoxic insults disrupt endoplasmic reticulum (ER) homeostasis, cause ER stress, and activate the unfolded protein response (UPR). The role of ER stress and UPR activation in hypersensitivity pneumonitis (HP) has not been described. HP is an immune-mediated interstitial lung disease that develops following repeated inhalation of various antigens in susceptible and sensitized individuals. The aim of this study was to investigate the lung expression and localization of the key effectors of the UPR, BiP/GRP78, CHOP, and sXBP1 in HP patients compared with control subjects. Furthermore, we developed a mouse model of HP to determine whether ER stress and UPR pathway are induced during this pathogenesis. In human control lungs, we observed weak positive staining for BiP in some epithelial cells and macrophages, while sXBP1 and CHOP were negative. Conversely, strong BiP, sXBP1- and CHOP-positive alveolar and bronchial epithelial, and inflammatory cells were identified in HP lungs. We also found apoptosis and autophagy markers colocalization with UPR proteins in HP lungs. Similar results were obtained in lungs from an HP mouse model. Our findings suggest that the UPR pathway is associated with the pathogenesis of HP.

Oral supplementation with postbiotics modulates the immune response produced by myxomatosis vaccination in wild rabbits.

Rabbits (Oryctolagus cuniculus) are vitally important species in the Iberian Peninsula ecosystem. However, since 1950, there has been a significant population decline, with major repercussions. This situation is mainly due to the presence of infectious diseases, such as myxomatosis, which is expanding and is characterized by severe and fatal clinical manifestations. Current control measures, mainly those based on vaccinations, are ineffective. Therefore, new strategies need to be developed and implemented. This study aimed to evaluate whether supplementation with postbiotic products modulates the immune response in wild rabbits vaccinated against myxomatosis. For this purpose, two groups of rabbits were established: a control group fed with standard feed ad libitum from weaning (28 days) until two months of age, and a treated group, which was fed under the same conditions but supplemented with postbiotics (3 kg/Tm). All the studied rabbits were vaccinated against this disease during weaning. In addition, a blood samples were obtained from all animals immediately before vaccination and 30 days later, which allowed us to evaluate the level of antibodies against myxomatosis virus (ELISA detection) and the relative expression of gene encoding to cytokines related to the immune response (IL6, TNFα and IFNγ), at both times of the experience. Weight and length measurements were also taken at both times to calculate body index and mean daily gain (MDG). No statistically significant differences in growth parameters were observed. There were also no differences in the serological response among groups. However, a relative underexpression of gene codifying to TNFα (p-value = 0.03683) and a higher expression on IFNγ (p-value = 0.045) were observed in the treated group. This modulation in cytokines could lead to less severe lesions in wild rabbit naturally infected with myxomatosis virus.

Has the balloon really burst? Analysis of "the UK-REBOA randomized clinical trial".

BACKGROUND: Uncontrolled hemorrhagic shock is a leading cause of early death after injury. Resuscitative endovascular balloon occlusion of the aorta (REBOA) represents a paradigm shift in achieving hemodynamic stability and its implementation still remain controversial in different settings. The recently published UK-REBOA Randomized Clinical Trial aimed to determine the effectiveness of REBOA in patients with hemorrhagic shock, concluding its increased mortality compared with standard care alone. METHODS: An adjustment of the statistical analysis was performed and a comprehensive analysis was proposed to address the study's limitations and demonstrate that these conclusions cannot be considered as benchmarks. RESULTS: Primary and secondary outcomes were analyzed using Bayesian logistic regression and generalized linear models suitable for the outcome distribution. No statistically significant differences were observed between the two groups for the primary outcome (p-value 0.3341) nor in most of the secondary outcomes. The results of the principal stratum analyses (to account for intercurrent events) also did not show significant differences after the statistical analysis tests. CONCLUSION: It cannot be stated that REBOA increases mortality compared with standard care alone in trauma patients with exsanguinating hemorrhage. Further studies and adequate simulation training programs in REBOA are critical to its successful implementation within a trauma system and to identify the optimum settings and patients.

Impact of Minimally Invasive Intra-Capsular Metatarsal Osteotomy on Plantar Pressure Decrease: A Cross-Sectional Study.

Background: Metatarsalgia is a common pathology that is initially treated conservatively, but failure to do so requires surgery, such as the minimally invasive distal metatarsal osteotomy (DICMO). Methods: In this prospective study of 65 patients with primary metatarsalgia who underwent DICMO, plantar pressures, American Orthopaedic Foot and Ankle Society MetaTarsoPhalangeal-InterPhalangeal scale (AOFAS-MTP-IP) and Visual Analog Scale (VAS) were evaluated pre-operatively and post-operatively and there was a subgroup in which an inclinometer was used to observe the importance of the inclination of the osteotomy. Results: The results show a significant reduction in plantar pressures after DICMO surgery without overloading the adjacent radii, especially in the subgroup with an inclinometer to guide the osteotomy. The AOFAS-MTP-IP scale evidenced a marked improvement in metatarsal function and alignment with scores close to normal. The VAS scale showed a substantial decrease in pain after DICMO osteotomy. Conclusions: DICMO, with an inclinometer for a 45° osteotomy, proved to be a safe and effective procedure for primary metatarsalgia, although further comparative studies are needed to confirm its superiority.

Dual-Time-Point 18F-FDG PET/CT in Infective Endocarditis: Impact of Delayed Imaging in the Definitive Diagnosis of Endocarditis.

Infective endocarditis (IE) is a major public health condition due to the associated high morbidity and mortality. Our objective was to evaluate the utility of dual-time 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG) Positron Emission Tomography/Computed Tomography (PET/CT) imaging in the diagnosis of active IE in patients with suspected native valve endocarditis (NVE) and prosthetic valve endocarditis (PVE). For this purpose, a retrospective study was carried out, including patients suspicious of NVE or PVE who underwent a dual-time-point 18F-FDG PET/CT. A final diagnosis was established by the Endocarditis Team after patient follow-up using all the available findings. Sixty-nine patients were assessed. A final diagnosis of NVE was established in 3 patients of the 34 by 18F-FDG PET/CT and in the case of PVE was established in 20 patients of the 35. A statistically significant association was found when evaluating the association between PET diagnosis at early acquisition and final diagnosis of IE (χ2 = 30.198, p < 0.001) and PET diagnosis at delayed acquisition for final diagnosis of IE (χ2 = 9.412, p = 0.002). Delayed PET/CT imaging determined the IE diagnosis in 16/58 of the studies. In conclusion, delayed 18F-FDG PET/CT imaging seems to be useful in improving the definitive diagnosis of IE.

Whole-body tumour burden on [18F]DCFPyL PET/CT in biochemical recurrence of prostate cancer: association with tumour biology and PSA kinetics.

PURPOSE: The objective was to assess the association between molecular imaging (mi) variables on [18F]DCFPyL-PET/CT with clinical and disease characteristics and prostate specific antigen (PSA) related variables in patients with biochemical recurrence of prostate cancer (BRPC). MATERIAL AND METHODS: We analysed patients with BRPC after radical treatment. We obtained clinical and PSA variables: International Society of Urology Pathology (ISUP) grade group, European Association of Urology (EAU) risk classification, PSA (PSA≤1ng/ml, 12), PSA doubling time (PSAdt) and PSA velocity (PSAvel). All PET/CT scans were reviewed with the assistance of automated Prostate Molecular Imaging Standardized Evaluation (aPROMISE) software and lesions' segmentation in positive scans was performed using this platform. Standardized uptake value (SUV) derived variables; tumour burden variables [whole-body tumour volume (wbTV), whole-body tumour lesion activity (wbTLA) and whole-body mi PSMA (wbPSMA)] and miTNM staging were obtained. Cut-off of PSA and kinetics able to predict PET/CT results were obtained. Associations between disease and mi variables were analysed using ANOVA, Kruskal-Wallis and Spearman's correlation tests. Multivariate analysis was also performed. RESULTS: Two hundred and seventy-five patients were studied. [18F]DCFPyL-PET/CT were positive in 165/275 patients. In multivariate analysis, moment of biochemical recurrence, ISUP group, PSA level and PSAvel showed significant association with the detection rate. miTNM showed significant association with PSA level (p<0.001) and kinetics (p<0.001), being higher in patients with metastatic disease. Both PSA and PSAvel showed moderate correlation with wbTV, wbTLA and wbPSMA (p<0.001). A weak correlation with SUVs was found. Mean wbTV, wbTLA and wbPSMA values were significantly higher in PSA > 2ng/ml, PSAdt ≤ 6 months and PSAvel ≥ 0.2ng/ml/month groups. Also, wbTV (p=0.039) and wbPSMA (p=0.020) were significantly higher in patients with ISUP grade group 5. PSA and PSAvel cut-offs (1.15 ng/ml and 0.065 ng/ml/month) were significantly associated with a positive PET/CT. CONCLUSION: Higher PSA values, unfavourable PSA kinetics and ISUP grade group 5 were robust predictive variables of larger tumour burden variables on [18F]DCFPyL PET/CT assessed by aPROMISE platform.

Elevated blood metal ion levels in patients undergoing instrumented spinal surgery: a systematic review and meta-analysis.

BACKGROUND CONTEXT: Elevated blood metal levels have been reported in patients after spinal surgery using metallic implants. Although some studies have suggested an association between heightened blood metal concentrations and potential adverse effects, estimates of the incidence of abnormal metal levels after spinal surgery have been inconsistent. PURPOSE: The aims of this systematic review and meta-analysis were to assess: (1) mean differences in blood metal ion levels between patients undergoing spinal fusion surgery and healthy controls, (2) odds of elevated blood metal ion levels after surgery compared to presurgery levels, and (3) pooled incidence of elevated blood metal ions overall and by metal type. STUDY DESIGN: Systematic review and meta-analysis. PATIENTS SAMPLE: The patient sample included 613 patients from 11 studies who underwent spinal surgery instrumentation. OUTCOME MEASURES: Blood metal ion concentrations and the incidence of patients with elevated metal levels compared with in those the control group. METHODS: A comprehensive search was conducted in PubMed, EMBASE, Scopus, and Cochrane Library to identify studies reporting blood metal ion levels after spinal fusion surgery. Mean differences (MD), odds ratios (OR), and incidence rates were pooled using random effects models. Heterogeneity was assessed using I2 statistics, and fixed-effects models were used if no heterogeneity was detected. Detailed statistical analysis was performed using the Review Manager version 5.4 software. RESULTS: The analysis included 11 studies, with a total of 613 patients. Mean blood metal ion levels were significantly higher after spinal fusion surgery (MD 0.56, 95% CI 0.17-0.96; I2=86%). Specifically, titanium levels were significantly elevated (MD 0.81, 95% CI 0.32-1.30; I2=47%). The odds of elevated blood metal ions were higher after surgery (OR 8.17, 95% CI 3.38-19.72; I2=41%), primarily driven by chromium (OR 23.50, 95% CI 5.56-99.31; I2=30%). The incidence of elevated chromium levels was found to be 66.98% (95% CI 42.31-91.65). CONCLUSION: In conclusion, blood metal ion levels, particularly titanium and chromium, were significantly increased after spinal fusion surgery compared to presurgery levels and healthy controls. Approximately 70% of the patients exhibited elevated blood levels of chromium and titanium.

Generation of Knockout Mouse Trophoblast Stem Cells by CRISPR/Cas9.

The placenta is the organ that dictates the reproductive outcome of mammalian pregnancy by supplying nutrients and oxygen to the developing fetus to sustain its normal growth. During early mammalian development, trophoblast cells are the earliest cell type to differentiate with multipotent capacity to generate the trophoblast components of the placenta. The isolation and use of mouse trophoblast stem cells (mTSCs) to model in vitro trophoblast differentiation, in combination with CRISPR/Cas9 genome editing technology, has provided tremendous insight into the molecular mechanisms governing early mouse placentation. By knocking out a specific gene of interest in mTSCs, researchers are shedding light onto the molecular pathways involved in normal placental development and pregnancy disorders associated with abnormal placentation. In this chapter, we provide a detailed protocol for the genetic modification of mTSCs by using CRISPR/Cas9 genome editing system.

CRISPR Activation in Mouse Trophoblast Stem Cells.

The placenta is a vital organ that regulates nutrient supply to the developing embryo during gestation. In mice, the placenta is composed of trophoblast lineage and mesodermal derivatives, which merge through the chorioallantoic fusion process in a critical event for the progression of placenta development. The trophoblast lineage is derived from self-renewing, multipotent cells known as mouse trophoblast stem cells (mTSCs). These cells are a valuable tool that allows scientists to comprehend the signals regulating major placental cell types' self-renewal and differentiation capacity. Recent advances in CRISPR-Cas9 genome editing applied in mTSCs have provided novel insights into the molecular networks involved in placentation. Here, we present a comprehensive CRISPR activation (CRISPRa) protocol based on the CRISPR/gRNA-directed synergistic activation mediator (SAM) method to overexpress specific target genes in mTSCs.

Incidence and risk factors of distal adjacent disc degeneration in adolescent idiopathic scoliosis patients undergoing fusion surgery: a systematic review and meta-analysis.

PURPOSE: The objective of this meta-analysis was to determine the incidence of disc degeneration in patients with surgically treated adolescent idiopathic scoliosis (AIS) and identify the associated risk factors. METHODS: PubMed, EMBASE, Scopus, and Cochrane Collaboration Library databases were searched. The outcomes of interest were the incidence of disc degeneration, SRS-22, and radiological risk factors. The lower instrumented vertebra (LIV) was also evaluated. Fixed effects were used if there was no evidence of heterogeneity. Statistical analysis was performed using Review Manager. RESULTS: A meta-analysis was conducted including nine studies with a total of 565 patients. The analysis revealed that the global incidence of intervertebral disc degeneration in patients with surgically treated AIS patients was 24.78% (95% CI 16.59-32.98%) 10 years after surgery, which significantly increased to 32.32% (95% CI 21.16-43.47% at an average of 13.8 years after surgery. Among patients with significant degenerative disc changes, the SRS-22 functional, self-image, and satisfaction domains showed significantly worse results (MD - 0.25, 95% CI - 0.44 to - 0.05; MD - 0.50, 95% CI - 0.75 to - 0.25; and MD - 0.34, 95% CI - 0.66 to - 0.03, respectively). Furthermore, instrumentation at or above the L3 level was associated with a lower incidence of intervertebral disc degeneration compared to instrumentation below the L3 level (OR 0.25, 95% CI 0.10-0.64). It was also found that the preoperative and final follow-up lumbar curve magnitudes (MD 8.11, 95% CI 3.82-12.41) as well as preoperative and final follow-up lumbar lordosis (MD 0.42, 95% CI - 3.81 to 4.65) were associated with adjacent disc degeneration. CONCLUSIONS: This meta-analysis demonstrated that the incidence of intervertebral disc degeneration significantly increased with long-term follow-up using fusion techniques, reaching up to 32% when patients were 28 years of age. Incomplete correction of deformity and fusion of levels below L3, were identified as negative prognostic factors. Furthermore, patients with disc degeneration showed worse functional outcomes.

Second radioiodine treatment in patients with differentiated thyroid carcinoma: Causes and effects.

INTRODUCTION: Patients with incomplete response to initial therapy of thyroid cancer can be managed with ongoing observation or potentially additional therapies. Our aim was to assess the effect of a second radioactive iodine treatment (RAIT) and its relationship with causes and clinical variables. MATERIAL AND METHODS: Patients undergoing a second RAIT for biochemical or structural incomplete response to initial therapy of DTC were retrospectively included (n=120). They were categorised based on the American Thyroid Association (ATA) classification of response to initial therapy. Patients were reclassified in the following 6-18 months after second RAIT based on imaging findings and measurements of thyroglobulin and antithyroglobulin antibody levels. The associations of a downgrading of response category and progression-free survival (PFS), and the related variables, were evaluated. RESULTS: Sixty-six patients (55%) had a downgrading on ATA response category after second RAIT. A significant interdependence of causes for second RAIT and outcomes was found (χ2=29.400, p=0.001), with patients with neck reoperation showing a higher rate of indeterminate or excellent responses. A significant association between ATA response to second RAIT and absence of structural progression was found (χ2=44.914, p<0.001), with less structural progression in patients with downgrading on ATA response (χ2=30.914, p<0.001). There was also significant interdependence to some clinical variables, such as AJCC stage (χ2=8.460, p=0.015), ATA risk classification (χ2=10.694, p=0.005) and initial N stage (χ2=8.485, p=0.004). CONCLUSIONS: In selected cases, a second RAIT could lead to more robust responses with a potential improvement in prognosis in patients with incomplete response to initial DTC treatment.

Digital Microscopy Augmented by Artificial Intelligence to Interpret Bone Marrow Samples for Hematological Diseases.

Analysis of bone marrow aspirates (BMAs) is an essential step in the diagnosis of hematological disorders. This analysis is usually performed based on a visual examination of samples under a conventional optical microscope, which involves a labor-intensive process, limited by clinical experience and subject to high observer variability. In this work, we present a comprehensive digital microscopy system that enables BMA analysis for cell type counting and differentiation in an efficient and objective manner. This system not only provides an accessible and simple method to digitize, store, and analyze BMA samples remotely but is also supported by an Artificial Intelligence (AI) pipeline that accelerates the differential cell counting process and reduces interobserver variability. It has been designed to integrate AI algorithms with the daily clinical routine and can be used in any regular hospital workflow.

Effects of feeding with a protein liquid supplement on productivity, mortality and health of Apis mellifera hives in southwestern Spain.

Colony collapse disorder (CCD) has affected bees worldwide in recent decades, with southwestern Spain being no exception. This disorder is one of the main causes of Apis mellifera mortality and is believed to be caused by environmental, social and sanitary conditions. Dietary supplementation can help to improve some parameters of the general status and sanitary condition of bees, such as infestation by certain recurrent pathogens, including Varroa destructor and Nosema ceranae, by enhancing immune and social response. Thus, the aim of this study was to test a liquid hydrolysed protein supplement on the health and general status of the hive in several apiaries with access to the same natural food and under similar climatic conditions. We selected two groups of ten hives (supplemented by either placebo or protein) from five apiaries where the number of adult bees, amount of brood (open and operculated), honey and pollen reserves, infestation by V. destructor, N. ceranae, deformed wing virus (DWV) and chronic bee paralysis virus (CBPV) were measured. Additionally, we assess the expression of four immune system-related genes and a gene encoding vitellogenin. At the end of this work, treated hives showed a significant increase in open brood and a decrease in V. destructor infestation. Also, these hives showed a significant decrease in the mortality rate after the cold season. Therefore, supplementation with this product improved the health of the hive and could be a promising tool against bee colony loss.

Analytical performance validation of aPROMISE platform for prostate tumor burden, index and dominant tumor assessment with 18F-DCFPyL PET/CT. A pilot study.

To validate the performance of automated Prostate Cancer Molecular Imaging Standardized Evaluation (aPROMISE) in quantifying total prostate disease burden with 18F-DCFPyL PET/CT and to evaluate the interobserver and histopathologic concordance in the establishment of dominant and index tumor. Patients with a recent diagnosis of intermediate/high-risk prostate cancer underwent 18F-DCFPyL-PET/CT for staging purpose. In positive-18F-DCFPyL-PET/CT scans, automated prostate tumor segmentation was performed using aPROMISE software and compared to an in-house semiautomatic-manual guided segmentation procedure. SUV and volume related variables were obtained with two softwares. A blinded evaluation of dominant tumor (DT) and index tumor (IT) location was assessed by both groups of observers. In histopathological analysis, Gleason, International Society of Urological Pathology (ISUP) group, DT and IT location were obtained. We compared all the obtained variables by both software packages using intraclass correlation coefficient (ICC) and Cohen's kappa coefficient (k) for the concordance analysis. Fifty-four patients with a positive 18F-DCFPyL PET/CT were evaluated. The ICC for the SUVmax, SUVpeak, SUVmean, tumor volume (TV) and total lesion activity (TLA) was: 1, 0.833, 0.615, 0.494 and 0.950, respectively (p < 0.001 in all cases). For DT and IT detection, a high agreement was observed between both softwares (k = 0.733; p < 0.001 and k = 0.812; p < 0.001, respectively) although the concordances with histopathology were moderate (p < 0001). The analytical validation of aPROMISE showed a good performance for the SUVmax, TLA, DT and IT definition in comparison to our in-house method, although the concordance was moderate with histopathology for DT and IT.