Evaluation of Reproductive Histology Response of Adult Fasciola hepatica in Goats Vaccinated with Cathepsin L Phage-Exposed Mimotopes.

Fasciolosis, a globally re-emerging zoonotic disease, is mostly caused by the parasitic infection with Fasciola hepatica, often known as the liver fluke. This disease has a considerable impact on livestock productivity. This study aimed to evaluate the fluke burdens and faecal egg counts in goats that were administered phage clones of cathepsin L mimotopes and then infected with F. hepatica metacercariae. Additionally, the impact of vaccination on the histology of the reproductive system, specifically related to egg generation in adult parasites, was examined. A total of twenty-four goats, which were raised in sheds, were divided into four groups consisting of six animals each. These groups were randomly assigned. The goats were then subjected to two rounds of vaccination. Each vaccination involved the administration of 1 × 1013 phage particles containing specific mimotopes for cathepsin L2 (group 1: PPIRNGK), cathepsin L1 (group 2: DPWWLKQ), and cathepsin L1 (group 3: SGTFLFS). The immunisations were carried out on weeks 0 and 4, and the Quil A adjuvant was used in combination with the mimotopes. The control group was administered phosphate-buffered saline (PBS) (group 4). At week 6, all groups were orally infected with 200 metacercariae of F. hepatica. At week 22 following the initial immunisation, the subjects were euthanised, and adult F. hepatica specimens were retrieved from the bile ducts and liver tissue, and subsequently quantified. The specimens underwent whole-mount histology for the examination of the reproductive system, including the testis, ovary, vitellaria, Mehlis' gland, and uterus. The mean fluke burdens following the challenge were seen to decrease by 50.4%, 62.2%, and 75.3% (p < 0.05) in goats that received vaccinations containing cathepsin L2 PPIRNGK, cathepsin L1 DPWWLKQ, and cathepsin L1 SGTFLFS, respectively. Animals that received vaccination exhibited a significant reduction in the production of parasite eggs. The levels of IgG1 and IgG2 isotypes in vaccinated goats were significantly higher than in the control group, indicating that protection is associated with the induction of a mixed Th1/Th2 immune response. The administration of cathepsin L to goats exhibits a modest level of efficacy in inducing histological impairment in the reproductive organs of liver flukes, resulting in a reduction in egg output.

Metastatic pancreatic and lung cancer patient in complete remission following immunotherapy: A case report and review of literature.

BACKGROUND: Metastatic pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with dispiriting survival data. Immunotherapy is a promising approach to many cancer types, but achieves poor outcomes in advanced PDAC due to its immunosuppressive tumor microenvironment. We describe a case of metastatic PDAC effectively treated with pembrolizumab. CASE SUMMARY: We report the case of a 67-year-old woman with unresectable locally advanced PDAC, treated with gemcitabine plus nab-paclitaxel followed by radiotherapy plus capecitabine. At nine months, pancreatic tumor progression was observed at the level of the hepatic hilum with the appearance of a new pulmonary nodule suggestive of a second primary, confirmed by left lung biopsy. Systemic immunotherapy was then initiated with pembrolizumab, an immune checkpoint inhibitor targeting programmed cell death protein-1 that covers the two tumor types. The patient showed a complete metabolic response that was maintained throughout the treatment. The patient continues to be disease-free at 5.6 years since the start of immunotherapy. CONCLUSION: These results suggest that the administration of pembrolizumab after chemoradiotherapy has a beneficial effect in patients with metastatic PDAC. To our knowledge, this is the first reported case of a patient with metastatic PDAC and metastatic lung cancer showing such a long-lasting complete response after pembrolizumab treatment without curative surgery. Further studies are required to determine biomarkers that identify PDAC patients most likely to benefit from this immunotherapy.

Performance of a vaginal self-collection device versus clinician collected cervical samples for the detection of high-risk human papillomavirus.

Objective: Screening for cervical cancer requires the participation of target women. Human papillomavirus (HPV) testing can be performed on vaginal self-samples and self-sampling can improve this participation. This study aims to validate the performance of the vaginal self-sampling device (Vitroveil®) to detect high risk human papillomavirus (hrHPV) in comparison to clinician collected samples and evaluate the degree of acceptability of the Vitroveil® device. Methods: A cross-sectional observational study was carried out in a cohort of 385 participating women (median age of 44 ± 10.47 years) attending primary care centers and cervical pathology services of Granada, Spain. Two paired samples (vaginal self-sample and clinician collected cervical sample) where collected from each participant to compare the detection of HPV with the Vitro HPV Screening assay (Vitro, Granada, Spain). A questionnaire was also provided to the participants to analyze the degree of satisfaction with the device and the preference for sampling method. Results: Overall concordance for hrHPV detection was substantial (ĸ 0.804). The prevalence of any hrHPV infection was higher in self-collected samples (30.6%) than in clinician-collected samples (24.3%). The participants found the self-sampling device easy to use and preferred self-collection as the collection method. Conclusion: The Vitroveil® self-sampling device enables safe and accruable hrHPV testing, obtaining equivalent results to those of the clinician collected samples. High acceptability of the device has been demonstrated among women in the study. Nevertheless, additional studies are necessary to verify the efficacy and reliability of the device's performance.

AmodalAppleSize_RGB-D dataset: RGB-D images of apple trees annotated with modal and amodal segmentation masks for fruit detection, visibility and size estimation.

The present dataset comprises a collection of RGB-D apple tree images that can be used to train and test computer vision-based fruit detection and sizing methods. This dataset encompasses two distinct sets of data obtained from a Fuji and an Elstar apple orchards. The Fuji apple orchard sub-set consists of 3925 RGB-D images containing a total of 15,335 apples annotated with both modal and amodal apple segmentation masks. Modal masks denote the visible portions of the apples, whereas amodal masks encompass both visible and occluded apple regions. Notably, this dataset is the first public resource to incorporate on-tree fruit amodal masks. This pioneering inclusion addresses a critical gap in existing datasets, enabling the development of robust automatic fruit sizing methods and accurate fruit visibility estimation, particularly in the presence of partial occlusions. Besides the fruit segmentation masks, the dataset also includes the fruit size (calliper) ground truth for each annotated apple. The second sub-set comprises 2731 RGB-D images capturing five Elstar apple trees at four distinct growth stages. This sub-set includes mean diameter information for each tree at every growth stage and serves as a valuable resource for evaluating fruit sizing methods trained with the first sub-set. The present data was employed in the research paper titled "Looking behind occlusions: a study on amodal segmentation for robust on-tree apple fruit size estimation" [1].

Circulating tumor cells in cancer-risk populations as a cancer interception tool.

Cancer interception (CI) is a new approach to cancer prevention and treatment in a cancer-risk population that aims to detect and treat pre-tumoral stages. It has several potential advantages over traditional cancer diagnosis and monitoring methods because it is non-invasive, making it less painful and risky than conventional biopsy procedures. The circulating tumor cells (CTCs), liquid biopsy family members, are essential for the CI approach; then, the liquid biopsy (LB) is used as a CI tool. LB can be performed frequently because of its easy sampling and early pathological stages, which allow repeated non-invasive monitoring of cancer progression and response to treatment. CTCs have been found in the bloodstream of several types of cancer patients, including in early-stage cancer and premalignant lesions, suggesting a tumor development role in cancer's early stages. This chapter will present foundational scientific studies addressing CI and the clinical impact of CTC screening in a population at risk for cancer.

Risk factors for functional dyspepsia, erosive and non-erosive gastroesophageal reflux disease: A cross-sectional study / Factores de riesgo en dispepsia funcional y enfermedad por reflujo gastroesofágico: un estudio transversal

Background: Conflicting data exists regarding risk factors associated with Gastroesophageal Reflux Disease (GERD) and Functional Dyspepsia (FD). Few studies examine anxiety/depression in relation to GERD phenotypes (Esophagitis/EE, and Non-Erosive Reflux Disease/NERD), FD, and Rome-IV syndromes. Our aim was to evaluate the association between epidemiological factors and comorbidities with GERD phenotypes, FD, and Rome-IV syndromes, as well as their relationship with anxiety/depression. Methods: 338 subjects were selected from 357 patients referred to three tertiary-centers for endoscopic evaluation. Every subject was interviewed individually to administer three validated questionnaires: GERD-Q, Rome-IV and HADS. Results: 45/338 patients were controls, 198/58.6% classified as GERD, 81/24.0% EE (49/14.5% symptomatic, and 32/9.5% asymptomatic), 117/34.6% NERD, 176/52.1% FD (43/12.7% epigastric pain syndrome, 36/10.7% postprandial distress syndrome, and 97/28.7% overlapping syndrome). 81 patients were mixed GERD-FD. Multivariate analysis found significant independent associations: age in NERD and FD; sex in EE, asymptomatic EE and FD; body mass index in NERD and FD; alcohol in EE; anxiety/depression in FD; use of calcium channel antagonists in EE; and inhalers in FD. We compared controls vs different groups/subgroups finding significantly more anxiety in NERD, FD, all Rome-IV syndromes, and mixed GERD-FD; more depression in FD, overlapping syndrome, and mixed GERD-FD; and higher levels of anxiety+depression in NERD, FD, overlapping syndrome, and mixed GERD-FD. Conclusions: NERD and FD share demographic and psychopathological risk factors which suggests that they may form part of the same pathophysiological spectrum. Regarding NERD anxiety was predominant, and in FD anxiety+depression, suggesting that both processes may require complementary psychological therapy.(AU)

Antecedentes: Existen datos controvertidos sobre los factores de riesgo asociados a la enfermedad por reflujo gastroesofágico (ERGE) y la dispepsia funcional (DF). Pocos estudios han evaluado la relación entre ansiedad/depresión y los diferentes fenotipos de la DF (criterios Roma IV) y de la ERGE (erosiva [EE] y no erosiva [NERD]). Nuestro objetivo fue valorar la asociación entre diferentes factores epidemiológicos y comorbilidades y los fenotipos de la ERGE, la DF y sus síndromes, y su relación con la ansiedad/depresión. Métodos: Se seleccionaron 338 pacientes entre 357 remitidos para estudio endoscópico en 3 hospitales terciarios. Cada uno fue entrevistado individualmente y completó 3 cuestionarios validados: GERD-Q, Roma IV y HADS. Resultados: Cuarenta y cinco de los 338 pacientes fueron controles. Se clasificaron 198/58,6% como ERGE, 81/24,0% como EE (49/14,5% sintomática y 32/9,5% asintomática), 117/34,6% como NERD y 176/52,1% como DF (43/12,7% síndrome de dolor epigástrico, 36/10,7% síndrome de molestias posprandiales y 97/28,7% solapamiento epigastralgia-molestias posprandiales). Ochenta y uno solapaban ERGE-DF. El análisis multivariante encontró las siguientes asociaciones significativas: edad en NERD y DF; sexo en EE, EE asintomática y DF; IMC en NERD y DF; alcohol en EE; ansiedad/depresión en DF; toma de antagonistas del calcio en EE e inhaladores en DF. Al comparar el grupo control vs. diferentes grupos/subgrupos encontramos significativamente más ansiedad en NERD, solapamiento DF-ERGE, DF y todos sus síndromes Roma IV; más depresión en DF, solapamientos epigastralgia-molestias posprandiales y ERGE-DF; y más ansiedad+depresión en NERD, DF y solapamientos epigastralgia-molestias posprandiales y ERGE-DF. Conclusiones: La DF y la NERD comparten factores de riesgo demográficos y psicopatológicos, lo que evidencia que forman parte de un mismo espectro fisiopatológico...(AU)

Defining the first bona fide cell model for SMARCA4-deficient, undifferentiated tumor.

The World Health Organization's tumor classification guidelines are frequently updated and renewed as knowledge of cancer biology advances. For instance, in 2021, a novel lung tumor subtype named SMARCA4-deficient, undifferentiated tumor (SMARCA4-dUT, code 8044/3) was included. To date, there is no defined cell model for SMARCA4-dUT that could be used to help thoracic clinicians and researchers in the study of this newly defined tumor type. As this tumor type was recently described, it is feasible that some cell models formerly classified as lung adenocarcinoma (LUAD) could now be better classified as SMARCA4-dUT. Thus, in this work, we aimed to identify a bona fide cell model for the experimental study of SMARCA4-dUT. We compared the differential expression profiles of 36 LUAD-annotated cell lines and 38 cell lines defined as rhabdoid in repositories. These comparative results were integrated with the mutation and expression profiles of the SWI/SNF complex members, and they were surveyed for the presence of the SMARCA4-dUT markers SOX2, SALL4, and CD34, measured by RT-qPCR and western blotting. Finally, the cell line with the paradigmatic SMARCA4-dUT markers was engrafted into immunocompromised mice to assess the histological morphology of the formed tumors and compare them with those formed by a bona fide LUAD cancer cell line. NCI-H522, formerly classified as LUAD, displayed expression profiles nearer to rhabdoid tumors than LUAD tumors. Furthermore, NCI-H522 has most of the paradigmatic features of SMARCA4-dUT: hemizygous inactivating mutation of SMARCA4, severe SMARCA2 downregulation, and high-level expression of stem cell markers SOX2 and SALL4. In addition, the engrafted tumors of NCI-H522 did not display a typical differentiated glandular structure as other bona fide LUAD cell lines (A549) do but had rather a largely undifferentiated morphology, characteristic of SMARCA4-dUT. Thus, we propose the NCI-H522 as the first bona fide cell line model of SMARCA4-dUT. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

microRNAs signature in relapse metastasis and de novo metastasis of breast cancer. A systematic review.

miRNAs have been widely identified as important players in cancer development and progression. Metastasis in breast cancer can occur as relapse of a treated primary tumour or at the time of diagnosis of the tumour. The aim of this review is to show if both metastasis are different molecular entities characterised by different miRNA signatures that could be studied as specific biomarkers for each entity. For this, we systematically searched the PubMed, Scopus and Web of Science databases. After searching and reviewing the literature, a total of 30 records were included in this review. Results showed a genetic signature including a total of 5 upregulated miRNAs in metastasis compared with early stages. Of them, miR-23b and miR-200c were exclusively present in relapse metastasis. Finally, we proposed a molecular signature for future studies that can be used as a complementary tool at clinical trials for the diagnosis and characterization of metastasis.

HPV Infection of the Oropharyngeal, Genital and Anal Mucosa and Associated Dysplasia in People Living with HIV.

BACKGROUND: The main objectives were to describe the prevalence of HPV, its genotypes and HPV-associated dysplastic lesions in the oropharyngeal mucosa of PLHIV and related factors. MATERIAL AND METHODS: This cross-sectional prospective study consecutively enrolled PLHIV attending our specialist outpatient units. At visit, HIV-related clinical and analytical variables were gathered, and oropharyngeal mucosa exudates were taken to detect HPV and other STIs by polymerase chain reaction. Samples were also taken from the anal canal of all participants and from the genital mucosa of the women for HPV detection/genotyping and cytological study. RESULTS: The 300 participants had a mean age of 45.1 years; 78.7% were MSM and 21.3% women; 25.3% had a history of AIDS; 99.7% were taking ART; and 27.3% had received an HPV vaccine. HPV infection prevalence in the oropharynx was 13%, with genotype 16 being the most frequent (2.3%), and none had dysplasia. Simultaneous infection with Treponema pallidum (HR: 4.02 (95% CI: 1.06-15.24)) and a history of anal HSIL or SCCA (HR: 21.52 (95% CI: 1.59-291.6)) were risk factors for oropharyngeal HPV infection, whereas ART duration (8.8 vs. 7.4 years) was a protective factor (HR: 0.989 (95% CI: 0.98-0.99)). CONCLUSIONS: The prevalence of HPV infection and dysplasia was low in the oropharyngeal mucosae. A higher exposure to ART was protective against oral HPV infection.

Role of Low-Risk HPV PCR Monoinfection in Screening for HSIL and Anal Cancer in Men Who Have Sex with Men Living with HIV.

To determine the value of low-risk human papillomavirus (HPV) PCR to screen for "high-grade anal squamous intraepithelial lesion and anal cancer" (HSIL-plus), rate of patients with low-grade anal squamous intraepithelial lesion (LSIL) progressing to HSIL-plus, and progression-related factors. Prospective, longitudinal study of consecutive MSM-LHIV attended between May 2010 and December 2021 and followed for 43 months (IQR: 12-76). HIV-related variables were gathered at baseline, performing anal cytology for HPV detection/genotyping, thin-layer cytological study, and high-resolution anoscopy (HRA). Follow-up was annual when HRA was normal or LSIL, and post-treatment in cases of HSIL-plus, re-evaluating sexual behavior, viral-immunological status, and HPV infection of anal mucosa. The 493 participants had mean age of 36 years: CD4 nadir < 200 cells/uL in 23.1%, virological failure in 4.1%, and tetravalent HPV vaccine > 5 years earlier in 15%. HSIL-plus was ruled out in patients with monoinfection by low-risk HPV genotype and normal cytology (100% sensitivity, 91.9% specificity, PPV 2.9%, and NPV 100%). Progression from LISL to HSIL-plus occurred in 4.27% of patients within 12 months (IQR: 12-12): risk factors were acquisition of high-risk (HR: 4.15; 95% CI: 1.14-15.03) and low-risk (HR: 3.68 95% CI: 1.04-12.94) HPV genotypes, specifically genotype 6 (HR: 4.47, 95% CI: 1.34-14.91), and history of AIDS (HR: 5.81 95% CI: 1.78-18.92). Monoinfection by LR-HPV genotypes in patients with normal cytology is not associated with anal cancer or precursor lesions. Progression from LSIL to HSIL-plus, observed in <5% of patients, was related to acquisition of HR and LR HPV genotypes, especially 6, and a history of AIDS.

Draft Genome Assembly of Stutzerimonas sp. Strain S1 and Achromobacter spanius Strain S4, Two Syringol-Metabolizing Bacteria Isolated from Compost Soil.

Two bacterial strains able to use syringol as a sole carbon source were isolated from compost. The isolates, named S1 and S4, were sequenced using the Illumina platform. The final assemblies contained 4.2 Mbp, 63% GC, and 3,912 genes for S1 and 6.2 Mbp, 64% GC, and 5,503 genes for S4.

Prevalence of transthyretin cardiac amyloidosis in elderly patients diagnosed with heart failure / Prevalencia de amiloidosis cardiaca por transtirretina en pacientes de edad avanzada con diagnóstico de insuficiencia cardiaca

Objective: There is increased interest in studying ATTR-CA, a pathology that primarily affects patients of geriatric age and is frequently underdiagnosed. We aim to establish the prevalence of ATTR-CA in a cohort of patients with a history of HFpEF and to describe its characteristics. Methods: We conducted a prospective observational study. Patients ≥75 years, clinical history of HFpEF, atrial dilation ≥34ml/m2 and left ventricular wall thickening >13mm, were included. Demographic and analytical parameters were collected, and a comprehensive geriatric assessment was performed, along with a transthoracic echocardiogram and cardiac scintigraphy. Finally, telephone follow-up was carried out at 6 and 12 months. Results: 50 patients were recruited, mean age 86±6 years, 54% women. Age and functional class (I–II vs. III–IV) were factors associated with presenting with ATTR-CA. Patients with positive scintigraphy had a median time to admission of 5.2 months (confidence interval [CI] 95% 0–10.9), while in those with negative scintigraphy, it was 12.2 months (95% CI 11.7–12.8); log-rank: p=0.064. Patients with positive scintigraphy had a median time to the combined endpoint (death and readmission) of 1.9 months (95% CI 0–6.1), and patients with negative scintigraphy of 11.9 months (95% CI 11.7–12); log-rank: p=0.027. Conclusions: ATTR-CA appears to be a prevalent etiology in elderly patients within the spectrum of HFpEF. Patients with a diagnosis of ATTR-CA had a shorter time to admission for HF and the combined event of death and admission than patients with a negative result on scintigraphy. (AU)

Objetivo: Existe un interés creciente por el estudio de AC-TTR, siendo esta una patología que afecta fundamentalmente a pacientes de edad avanzada y que es frecuentemente infradiagnosticada. Nuestro objetivo fue establecer la prevalencia de AC-TTR en una cohorte de pacientes con historia de ICFEp y describir sus características. Métodos: Estudio observacional prospectivo. Se incluyeron pacientes ≥75 años, con historia clínica de ICFEp, dilatación auricular ≥34ml/m2 y engrosamiento de la pared del ventrículo izquierdo >13mm. Se recogieron datos analíticos y demográficos, así como de la valoración geriátrica integral y se realizó un ecocardiograma transtorácico y una gammagrafía cardiaca. Finalmente se realizó seguimiento telefónico a los 6 y 12 meses. Resultados: Se incluyó a 50 pacientes, edad media 86±6 años, 54% mujeres. La edad y la clase funcional NYHA (I-II vs. III-IV) se asociaron con mayor riesgo de presentar AC-TTR. Los pacientes con gammagrafía positiva tuvieron una mediana de tiempo al ingreso de 5,2 meses (intervalo de confianza [IC] 95% 0-10,9), frente a aquellos con gammagrafía negativa que fue de 12,2 meses (IC 95% 11,7-12,8); log-rank: p=0,064. Los pacientes con gammagrafía positiva presentaron una mediana de tiempo al evento combinado (muerte y reingreso) de 1,9 meses (IC 95% 0-6,1), mientras que en aquellos con resultado negativo fue de 11,9 meses (IC 95% 11,7-12); log-rank: p=0.027. Conclusiones: La AC-TTR supone una etiología prevalente de insuficiencia cardiaca, dentro del espectro de la ICFEp, en pacientes de edad avanzada. Los individuos con diagnóstico de AC-TTR presentaron un menor tiempo al ingreso por insuficiencia cardiaca y al evento combinado de muerte y reingreso frente a aquellos pacientes con resultado negativo en la gammagrafía. (AU)

Risk factors for functional dyspepsia, erosive and non-erosive gastroesophageal reflux disease: A cross-sectional study.

BACKGROUND: Conflicting data exists regarding risk factors associated with Gastroesophageal Reflux Disease (GERD) and Functional Dyspepsia (FD). Few studies examine anxiety/depression in relation to GERD phenotypes (Esophagitis/EE, and Non-Erosive Reflux Disease/NERD), FD, and Rome-IV syndromes. Our aim was to evaluate the association between epidemiological factors and comorbidities with GERD phenotypes, FD, and Rome-IV syndromes, as well as their relationship with anxiety/depression. METHODS: 338 subjects were selected from 357 patients referred to three tertiary-centers for endoscopic evaluation. Every subject was interviewed individually to administer three validated questionnaires: GERD-Q, Rome-IV and HADS. RESULTS: 45/338 patients were controls, 198/58.6% classified as GERD, 81/24.0% EE (49/14.5% symptomatic, and 32/9.5% asymptomatic), 117/34.6% NERD, 176/52.1% FD (43/12.7% epigastric pain syndrome, 36/10.7% postprandial distress syndrome, and 97/28.7% overlapping syndrome). 81 patients were mixed GERD-FD. Multivariate analysis found significant independent associations: age in NERD and FD; sex in EE, asymptomatic EE and FD; body mass index in NERD and FD; alcohol in EE; anxiety/depression in FD; use of calcium channel antagonists in EE; and inhalers in FD. We compared controls vs different groups/subgroups finding significantly more anxiety in NERD, FD, all Rome-IV syndromes, and mixed GERD-FD; more depression in FD, overlapping syndrome, and mixed GERD-FD; and higher levels of anxiety+depression in NERD, FD, overlapping syndrome, and mixed GERD-FD. CONCLUSIONS: NERD and FD share demographic and psychopathological risk factors which suggests that they may form part of the same pathophysiological spectrum. Regarding NERD anxiety was predominant, and in FD anxiety+depression, suggesting that both processes may require complementary psychological therapy.

Prevalence of transthyretin cardiac amyloidosis in elderly patients diagnosed with heart failure.

OBJECTIVE: There is increased interest in studying ATTR-CA, a pathology that primarily affects patients of geriatric age and is frequently underdiagnosed. We aim to establish the prevalence of ATTR-CA in a cohort of patients with a history of HFpEF and to describe its characteristics. METHODS: We conducted a prospective observational study. Patients ≥75 years, clinical history of HFpEF, atrial dilation ≥34ml/m2 and left ventricular wall thickening >13mm, were included. Demographic and analytical parameters were collected, and a comprehensive geriatric assessment was performed, along with a transthoracic echocardiogram and cardiac scintigraphy. Finally, telephone follow-up was carried out at 6 and 12 months. RESULTS: 50 patients were recruited, mean age 86±6 years, 54% women. Age and functional class (I-II vs. III-IV) were factors associated with presenting with ATTR-CA. Patients with positive scintigraphy had a median time to admission of 5.2 months (confidence interval [CI] 95% 0-10.9), while in those with negative scintigraphy, it was 12.2 months (95% CI 11.7-12.8); log-rank: p=0.064. Patients with positive scintigraphy had a median time to the combined endpoint (death and readmission) of 1.9 months (95% CI 0-6.1), and patients with negative scintigraphy of 11.9 months (95% CI 11.7-12); log-rank: p=0.027. CONCLUSIONS: ATTR-CA appears to be a prevalent etiology in elderly patients within the spectrum of HFpEF. Patients with a diagnosis of ATTR-CA had a shorter time to admission for HF and the combined event of death and admission than patients with a negative result on scintigraphy.

Anorectal malignant melanoma, a diagnostic challenge.

Malignant anorectal melanoma is an extremely rare cause of rectal neoplasia, accounting for less than 1% of all melanomas and about 4% of all malignant colorectal neoplasms. We present the endoscopic and pathological images of a case in our clinical practice.

Isotonic regression for metallic microstructure data: estimation and testing under order restrictions.

Investigating the main determinants of the mechanical performance of metals is not a simple task. Already known physically inspired qualitative relations between 2D microstructure characteristics and 3D mechanical properties can act as the starting point of the investigation. Isotonic regression allows to take into account ordering relations and leads to more efficient and accurate results when the underlying assumptions actually hold. The main goal in this paper is to test order relations in a model inspired by a materials science application. The statistical estimation procedure is described considering three different scenarios according to the knowledge of the variances: known variance ratio, completely unknown variances, and variances under order restrictions. New likelihood ratio tests are developed in the last two cases. Both parametric and non-parametric bootstrap approaches are developed for finding the distribution of the test statistics under the null hypothesis. Finally an application on the relation between geometrically necessary dislocations and number of observed microstructure precipitations is shown.

Generation of a H9 Clonal Cell Line With Inducible Expression of NUP98-KDM5A Fusion Gene in the AAVS1 Safe Harbor Locus.

Pediatric acute myeloid leukemia (AML) is a rare and heterogeneous disease that remains the major cause of mortality in children with leukemia. To improve the outcome of pediatric AML we need to gain knowledge on the biological bases of this disease. NUP98-KDM5A (NK5A) fusion protein is present in a particular subgroup of young pediatric patients with poor outcome. We report the generation and characterization of human Embryonic Stem Cell (hESC) clonal lines with inducible expression of NK5A. Temporal control of NK5A expression during hematopoietic differentiation from hESC will be critical for elucidating its participation during the leukemogenic process.

A Data-Driven Approach for Studying the Influence of Carbides on Work Hardening of Steel.

This study proposes a new approach to determine phenomenological or physical relations between microstructure features and the mechanical behavior of metals bridging advanced statistics and materials science in a study of the effect of hard precipitates on the hardening of metal alloys. Synthetic microstructures were created using multi-level Voronoi diagrams in order to control microstructure variability and then were used as samples for virtual tensile tests in a full-field crystal plasticity solver. A data-driven model based on Functional Principal Component Analysis (FPCA) was confronted with the classical Voce law for the description of uniaxial tensile curves of synthetic AISI 420 steel microstructures consisting of a ferritic matrix and increasing volume fractions of M23C6 carbides. The parameters of the two models were interpreted in terms of carbide volume fractions and texture using linear mixed-effects models.