Immunoassay interferences: laboratory pitfall in the diagnosis of adrenocortical carcinoma.

A woman in her late 50s with recent onset of hypertension, diabetes, lumbar pain and unintentional weight loss was diagnosed with a cortisol and androgen-producing adrenal mass. Despite this, serum adrenocorticotropic hormone (ACTH) concentration was inappropriately elevated, which was investigated thoroughly. Investigations included a brain magnetic resonance imaging to exclude concomitant pituitary adenoma, a corticotropin-releasing hormone stimulation test and a gallium-68 DOTATATE and 18F-FDOPA PET scan, both excluding ectopic ACTH production. Considering the disparity between clinical presentation and biochemical results, the ACTH was reanalysed using the Cobas immunoassay (Roche, Switzerland), ultimately unveiling the cause for ACTH elevation. ACTH levels had previously been measured with ACTH Immulite (Siemens, Germany), a two-site immunoassay which is prone to interferences causing falsely elevated ACTH concentrations. Inaccurate laboratory levels can lead to diagnosis delay and unnecessary diagnostic procedures and a close communication between the physicians and laboratorians is of utmost importance.

How Fish Population Genomics Can Promote Sustainable Fisheries: A Road Map.

Maintenance of genetic diversity in marine fishes targeted by commercial fishing is a grand challenge for the future. Most of these species are abundant and therefore important for marine ecosystems and food security. Here, we present a road map of how population genomics can promote sustainable fisheries. In these species, the development of reference genomes and whole genome sequencing is key, because genetic differentiation at neutral loci is usually low due to large population sizes and gene flow. First, baseline allele frequencies representing genetically differentiated populations within species must be established. These can then be used to accurately determine the composition of mixed samples, forming the basis for population demographic analysis to inform sustainably set fish quotas. SNP-chip analysis is a cost-effective method for determining baseline allele frequencies and for population identification in mixed samples. Finally, we describe how genetic marker analysis can transform stock identification and management.

In vitro cross-talk between metastasis-competent circulating tumor cells and platelets in colon cancer: a malicious association during the harsh journey in the blood.

Background: Platelets are active players in hemostasis, coagulation and also tumorigenesis. The cross-talk between platelets and circulating tumor cells (CTCs) may have various pro-cancer effects, including promoting tumor growth, epithelial-mesenchymal transition (EMT), metastatic cell survival, adhesion, arrest and also pre-metastatic niche and metastasis formation. Interaction with CTCs might alter the platelet transcriptome. However, as CTCs are rare events, the cross-talk between CTCs and platelets is poorly understood. Here, we used our established colon CTC lines to investigate the colon CTC-platelet cross-talk in vitro and its impact on the behavior/phenotype of both cell types. Methods: We exposed platelets isolated from healthy donors to thrombin (positive control) or to conditioned medium from three CTC lines from one patient with colon cancer and then we monitored the morphological and protein expression changes by microscopy and flow cytometry. We then analyzed the transcriptome by RNA-sequencing of platelets indirectly (presence of a Transwell insert) co-cultured with the three CTC lines. We also quantified by reverse transcription-quantitative PCR the expression of genes related to EMT and cancer development in CTCs after direct co-culture (no Transwell insert) with platelets. Results: We observed morphological and transcriptomic changes in platelets upon exposure to CTC conditioned medium and indirect co-culture (secretome). Moreover, the expression levels of genes involved in EMT (p < 0.05) were decreased in CTCs co-cultured with platelets, but not of genes encoding mesenchymal markers (FN1 and SNAI2). The expression levels of genes involved in cancer invasiveness (MYC, VEGFB, IL33, PTGS2, and PTGER2) were increased. Conclusion: For the first time, we studied the CTC-platelet cross-talk using our unique colon CTC lines. Incubation with CTC conditioned medium led to platelet aggregation and activation, supporting the hypothesis that their interaction may contribute to preserve CTC integrity during their journey in the bloodstream. Moreover, co-culture with platelets influenced the expression of several genes involved in invasiveness and EMT maintenance in CTCs.

Domestic Violence against LGBTI People: Perspectives of Portuguese Education Professionals.

Lesbian, gay, bisexual, trans and intersex (LGBTI) people are more likely to be exposed to domestic violence than the rest of the population. Using a descriptive qualitative methodology, 28 professionals from the educational sector, aged between 28 and 64 years old (M = 44.5), were interviewed to describe and understand their perspectives on the sector's ability to support, intervene and get involved with LGBTI people and, particularly, with victims or former victims of domestic violence. Through a thematic content analysis, three main themes emerged: (i) life trajectories of LGBTI people; (ii) domestic violence perpetrated against LGBTI people; and (iii) training of the educational sector to intervene with LGBTI people. The results show that Portuguese education professionals are not trained to recognize and intervene with LGBTI people and, in particular, with those who are victims of domestic violence, since they are unaware of the existence of protocols and/or guidelines for detecting and preventing risk situations among students. Furthermore, the curricular plan fails in the coverage of domestic violence and LGBTI-related topics, although the National Strategy for Citizenship Education has been implemented in Portugal since 2017. Findings suggest the need to invest in education professionals' training.

Tumor-educated platelet blood tests for Non-Small Cell Lung Cancer detection and management.

Liquid biopsy approaches offer a promising technology for early and minimally invasive cancer detection. Tumor-educated platelets (TEPs) have emerged as a promising liquid biopsy biosource for the detection of various cancer types. In this study, we processed and analyzed the TEPs collected from 466 Non-small Cell Lung Carcinoma (NSCLC) patients and 410 asymptomatic individuals (controls) using the previously established thromboSeq protocol. We developed a novel particle-swarm optimization machine learning algorithm which enabled the selection of an 881 RNA biomarker panel (AUC 0.88). Herein we propose and validate in an independent cohort of samples (n = 558) two approaches for blood samples testing: one with high sensitivity (95% NSCLC detected) and another with high specificity (94% controls detected). Our data explain how TEP-derived spliced RNAs may serve as a biomarker for minimally-invasive clinical blood tests, complement existing imaging tests, and assist the detection and management of lung cancer patients.

Combinatorial Blood Platelets-Derived circRNA and mRNA Signature for Early-Stage Lung Cancer Detection.

Despite the diversity of liquid biopsy transcriptomic repertoire, numerous studies often exploit only a single RNA type signature for diagnostic biomarker potential. This frequently results in insufficient sensitivity and specificity necessary to reach diagnostic utility. Combinatorial biomarker approaches may offer a more reliable diagnosis. Here, we investigated the synergistic contributions of circRNA and mRNA signatures derived from blood platelets as biomarkers for lung cancer detection. We developed a comprehensive bioinformatics pipeline permitting an analysis of platelet-circRNA and mRNA derived from non-cancer individuals and lung cancer patients. An optimal selected signature is then used to generate the predictive classification model using machine learning algorithm. Using an individual signature of 21 circRNA and 28 mRNA, the predictive models reached an area under the curve (AUC) of 0.88 and 0.81, respectively. Importantly, combinatorial analysis including both types of RNAs resulted in an 8-target signature (6 mRNA and 2 circRNA), enhancing the differentiation of lung cancer from controls (AUC of 0.92). Additionally, we identified five biomarkers potentially specific for early-stage detection of lung cancer. Our proof-of-concept study presents the first multi-analyte-based approach for the analysis of platelets-derived biomarkers, providing a potential combinatorial diagnostic signature for lung cancer detection.

The evolution of white-tailed jackrabbit camouflage in response to past and future seasonal climates.

The genetic basis of adaptive traits has rarely been used to predict future vulnerability of populations to climate change. We show that light versus dark seasonal pelage in white-tailed jackrabbits (Lepus townsendii) tracks snow cover and is primarily determined by genetic variation at endothelin receptor type B (EDNRB), corin serine peptidase (CORIN), and agouti signaling protein (ASIP). Winter color variation was associated with deeply divergent alleles at these genes, reflecting selection on both ancestral and introgressed variation. Forecasted reductions in snow cover are likely to induce widespread camouflage mismatch. However, simulated populations with variation for darker winter pelage are predicted to adapt rapidly, providing a trait-based genetic framework to facilitate evolutionary rescue. These discoveries demonstrate how the genetic basis of climate change adaptation can inform conservation.

Fill in the blank for fashion complementary outfit product Retrieval: VISUM summer school competition.

Every year, the VISion Understanding and Machine intelligence (VISUM) summer school runs a competition where participants can learn and share knowledge about Computer Vision and Machine Learning in a vibrant environment. 2021 VISUM's focused on applying those methodologies in fashion. Recently, there has been an increase of interest within the scientific community in applying computer vision methodologies to the fashion domain. That is highly motivated by fashion being one of the world's largest industries presenting a rapid development in e-commerce mainly since the COVID-19 pandemic. Computer Vision for Fashion enables a wide range of innovations, from personalized recommendations to outfit matching. The competition enabled students to apply the knowledge acquired in the summer school to a real-world problem. The ambition was to foster research and development in fashion outfit complementary product retrieval by leveraging vast visual and textual data with domain knowledge. For this, a new fashion outfit dataset (acquired and curated by FARFETCH) for research and benchmark purposes is introduced. Additionally, a competitive baseline with an original negative sampling process for triplet mining was implemented and served as a starting point for participants. The top 3 performing methods are described in this paper since they constitute the reference state-of-the-art for this particular problem. To our knowledge, this is the first challenge in fashion outfit complementary product retrieval. Moreover, this joint project between academia and industry brings several relevant contributions to disseminating science and technology, promoting economic and social development, and helping to connect early-career researchers to real-world industry challenges.

The Portuguese version of the visual vertigo analog scale

Abstract Objectives: Visual vertigo occurs after a vestibular disorder compromising daily living. It can be assessed by "the Visual Vertigo Analogue Scale" (VVAS), a self-administered questionnaire without Portuguese version. To perform the translation, cross cultural adaptation, and validation of VVAS from English to Portuguese. Methods: Prospective study involving the translation and cross-cultural adaptation of the VVAS into the Portuguese language, according to recognized guidelines. It was completed by 63 healthy controls and 198 participants with vestibulopathy who also completed the Dizziness Handicap Inventory (DHI) to further explore the link between DHI and VVAS. Groups were compared for severity of visual vertigo and VVAS reliability and internal consistency were tested. Results: The VVAS score was significantly higher in vestibular group (p < 0.001). A Cronbach's α of 0.9 confirmed the valid internally consistent of the applied version. The severity score of VVAS showed a positive strong correlation with DHI (p < 0.0001). Conclusion: The present Portuguese translation of the scale showed satisfactory properties for the assessment of self-perceived and severity of visual vertigo in a significant group of vestibular Portuguese patients. Level of evidence: 2.

The Portuguese version of the visual vertigo analog scale.

OBJECTIVES: Visual vertigo occurs after a vestibular disorder compromising daily living. It can be assessed by "the Visual Vertigo Analogue Scale" (VVAS), a self-administered questionnaire without Portuguese version. To perform the translation, cross cultural adaptation, and validation of VVAS from English to Portuguese. METHODS: Prospective study involving the translation and cross-cultural adaptation of the VVAS into the Portuguese language, according to recognized guidelines. It was completed by 63 healthy controls and 198 participants with vestibulopathy who also completed the Dizziness Handicap Inventory (DHI) to further explore the link between DHI and VVAS. Groups were compared for severity of visual vertigo and VVAS reliability and internal consistency were tested. RESULTS: The VVAS score was significantly higher in vestibular group (p < 0.001). A Cronbach's α of 0.9 confirmed the valid internally consistent of the applied version. The severity score of VVAS showed a positive strong correlation with DHI (p < 0.0001). CONCLUSION: The present Portuguese translation of the scale showed satisfactory properties for the assessment of self-perceived and severity of visual vertigo in a significant group of vestibular Portuguese patients.

Detection and localization of early- and late-stage cancers using platelet RNA.

Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I-IV cancer patients and in half of 352 stage I-III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.

Attitudes of Portuguese Judges and Victim Support Professionals Toward Intimate Partner Homicide Committed by Women.

This investigation analyzed the attitudes of Portuguese judges and victim support professionals toward intimate partner homicide committed by women. By administering an online survey disseminated by the Portuguese Superior Council for the Magistracy and the Commission for Citizenship and Gender Equality, we found that both groups of professionals are not always aligned in their attitudes toward domestic violence and intimate partner homicide, which could jeopardize the articulation between both sectors needed for an effective preventive intervention. However, most professionals of both groups tend to disagree that women provoke their aggressors or lie about their condition as victims of domestic violence and agree that there is a need for increased security and prevention of intimate partner homicides against female and male victims when reporting domestic violence.

The Analysis of Platelet-Derived circRNA Repertoire as Potential Diagnostic Biomarker for Non-Small Cell Lung Cancer.

Tumor-educated Platelets (TEPs) have emerged as rich biosources of cancer-related RNA profiles in liquid biopsies applicable for cancer detection. Although human blood platelets have been found to be enriched in circular RNA (circRNA), no studies have investigated the potential of circRNA as platelet-derived biomarkers for cancer. In this proof-of-concept study, we examine whether the circRNA signature of blood platelets can be used as a liquid biopsy biomarker for the detection of non-small cell lung cancer (NSCLC). We analyzed the total RNA, extracted from the platelet samples collected from NSCLC patients and asymptomatic individuals, using RNA sequencing (RNA-Seq). Identification and quantification of known and novel circRNAs were performed using the accurate CircRNA finder suite (ACFS), followed by the differential transcript expression analysis using a modified version of our thromboSeq software. Out of 4732 detected circRNAs, we identified 411 circRNAs that are significantly (p-value < 0.05) differentially expressed between asymptomatic individuals and NSCLC patients. Using the false discovery rate (FDR) of 0.05 as cutoff, we selected the nuclear receptor-interacting protein 1 (NRIP1) circRNA (circNRIP1) as a potential biomarker candidate for further validation by reverse transcription-quantitative PCR (RT-qPCR). This analysis was performed on an independent cohort of platelet samples. The RT-qPCR results confirmed the RNA-Seq data analysis, with significant downregulation of circNRIP1 in platelets derived from NSCLC patients. Our findings suggest that circRNAs found in blood platelets may hold diagnostic biomarkers potential for the detection of NSCLC using liquid biopsies.

Multiresistent Cupriavidus pauculus infection in an immunocompromised elderly patient.

Cupriavidus pauculus is a gram-negative bacillus aerobic bacteria widely distributed in nature that can cause, in rare cases, serious infections both in immunocompromised and immunocompetent patients. We describe a case of an elderly patient admitted in emergency room with septic shock and diagnosed with a urinary tract infection. During his hospital stay, his clinical and analytical conditions have deteriorated. Blood cultures were positive for C. pauculus only sensitive to minocycline. Despite every effort, due to multiple comorbidities and a nosocomial pneumonia, the patient ends up dying.

Individual Resilience Interventions: A Systematic Review in Adult Population Samples over the Last Decade.

Resilience interventions have been gaining importance among researchers due to their potential to provide well-being and reduce the prevalence of mental disorders that are becoming an increasing concern, especially in Western countries, because of the costs associated. The purpose of this systematic review is to identify the intervention studies carried out in the last decade in adult population samples, evaluate their methodological quality and highlight the trends of these types of interventions. This review was performed using systematic literature searches in the following electronic databases: B-on, PubMed, PsycNet and Science Direct. The application of eligibility criteria resulted in the inclusion of 38 articles, of which 33 were randomized controlled trials and the other five were nonrandomized controlled studies. Although most studies showed statistical significance for their results, these were constrained by the great heterogeneity of the studies, the lack of power of the samples and their fair methodological quality. Therefore, it is important to consolidate the theoretical basis and standardize certain methodologies so that the effects of the interventions can be compared through a meta-analysis.

Treatment-induced diabetes neuropathy: reminder of an important clinical lesson.

Treatment-induced neuropathy of diabetes (TIND) is an acute, painful and rare complication of intensive glycaemic control in diabetes. We present a case of a 32-year-old man with sudden onset of severe lower limb pain. It worsened progressively and was refractory to analgesic and muscle relaxant therapies. It became so severe that the patient was impossible to stand, causing a marked impact on his daily life. He had a history of type 1 diabetes, diagnosed 3 years ago, and an episode of deep vein thrombosis of the left leg, 4 years ago. While completing an extensive workup, various analgesic adjustments were made, with no improvement. After careful revision of his medical data, a significant reduction of his A1C 6 months before the appearance of symptoms was noticed. A diagnosis of TIND was made. The patient was treated with amitriptyline and showed noticeable improvement after the first month.

Long-term continuous positive airway pressure treatment ameliorates biological clock disruptions in obstructive sleep apnea.

BACKGROUND: Obstructive Sleep Apnea (OSA) is a highly prevalent and underdiagnosed sleep disorder. Recent studies suggest that OSA might disrupt the biological clock, potentially causing or worsening OSA-associated comorbidities. However, the effect of OSA treatment on clock disruption is not fully understood. METHODS: The impact of OSA and short- (four months) and long-term (two years) OSA treatment, with Continuous Positive Airway Pressure (CPAP), on the biological clock was investigated at four time points within 24 h, in OSA patients relative to controls subjects (no OSA) of the same sex and age group, in a case-control study. Plasma melatonin and cortisol, body temperature and the expression levels and rhythmicity of eleven clock genes in peripheral blood mononuclear cells (PBMCs) were assessed. Additional computational tools were used for a detailed data analysis. FINDINGS: OSA impacts on clock outputs and on the expression of several clock genes in PBMCs. Neither short- nor long-term treatment fully reverted OSA-induced alterations in the expression of clock genes. However, long-term treatment was able to re-establish levels of plasma melatonin and cortisol and body temperature. Machine learning methods could discriminate controls from untreated OSA patients. Following long-term treatment, the distinction between controls and patients disappeared, suggesting a closer similarity of the phenotypes. INTERPRETATION: OSA alters biological clock-related characteristics that differentially respond to short- and long-term CPAP treatment. Long-term CPAP was more efficient in counteracting OSA impact on the clock, but the obtained results suggest that it is not fully effective. A better understanding of the impact of OSA and OSA treatment on the clock may open new avenues to OSA diagnosis, monitoring and treatment.

Incomplete lineage sorting and ancient admixture, and speciation without morphological change in ghost-worm cryptic species.

Morphologically similar species, that is cryptic species, may be similar or quasi-similar owing to the deceleration of morphological evolution and stasis. While the factors underlying the deceleration of morphological evolution or stasis in cryptic species remain unknown, decades of research in the field of paleontology on punctuated equilibrium have originated clear hypotheses. Species are expected to remain morphologically identical in scenarios of shared genetic variation, such as hybridization and incomplete lineage sorting, or in scenarios where bottlenecks reduce genetic variation and constrain the evolution of morphology. Here, focusing on three morphologically similar Stygocapitella species, we employ a whole-genome amplification method (WGA) coupled with double-digestion restriction-site associated DNA sequencing (ddRAD) to reconstruct the evolutionary history of the species complex. We explore population structure, use population-level statistics to determine the degree of connectivity between populations and species, and determine the most likely demographic scenarios which generally reject for recent hybridization. We find that the combination of WGA and ddRAD allowed us to obtain genomic-level data from microscopic eukaryotes (∼1 millimetre) opening up opportunities for those working with population genomics and phylogenomics in such taxa. The three species share genetic variance, likely from incomplete lineage sorting and ancient admixture. We speculate that the degree of shared variation might underlie morphological similarity in the Atlantic species complex.

Depression preceding the diagnosis of pancreatic cancer.

Pancreatic cancer is the tumour related to higher rates of depression. Several papers have validated the association between pancreatic cancer and depression. It was noticed that in some cases the psychiatric symptoms precede the somatic ones. We present a case of a progressive and incapacitating diffuse abdominal pain, initially attributed to psychosomatic disorder. This hindered a timely correct diagnosis leading to a poor outcome. A pancreatic adenocarcinoma in an unresectable stage was confirmed by histopathology. The patient underwent chemotherapy.