Miracle-dz/UniFAR-FTUs huggingface dataset:
Critical Results Reporting in Portuguese Hospital Laboratories: State-of-the-Art

Introduction This survey aimed to assess the state-of-the-art of current practices on critical results reporting among Portuguese Clinical Pathology Laboratories. The results of the survey will set basis for future standardization and national guideline development. Materials and methods The survey was transmitted to 49 Clinical Pathology Laboratories among public hospitals inserted in the Portuguese National Health System. In 27 questions, laboratories were asked about their critical results procedures, critical results list, reporting and further education. Data were analyzed using Microsoft Excel v.2016 and MedCalc Statistical Software version 12.5. 0.0 (Ostend, Belgium). Where applicable, the comparison of proportions was used to estimate the level of significance (P<0.05). Results The response rate was 44/49 (90%), including 36 participants with a defined critical results reporting procedure. Among them, 31 laboratories defined a critical results list, mainly based on published literature (27/31). There was a statistically significant number of laboratories (P=0.019, 24/30) that report different critical results depending on the patient’s age, but regardless of disease, ethnicity and location (P>0.05). The majority of laboratories (60%) report critical results via telephone within 15 minutes. Critical results are usually reported by clinical pathologists to physicians. Twenty-five laboratories periodically reevaluate their critical results list. Conclusion Despite the fact that most of the Portuguese hospitals have a critical results policy, this survey showed high variability among the hospitals concerning critical results reporting practices and critical results list. This survey points out that nationally established procedures and guidelines are urgent step for critical results standardization.
Vascular depression for radiology: A review of the construct, methodology, and diagnosis

Vascular depression (VD) as defined by magnetic resonance imaging (MRI) has been proposed as a unique subtype of late-life depression. The VD hypothesis posits that cerebrovascular disease, as characterized by the presence of MRI-defined white matter hyperintensities, contributes to and increases the risk for depression in older adults. VD is also accompanied by cognitive impairment and poor antidepressant treatment response. The VD diagnosis relies on MRI findings and yet this clinical entity is largely unfamiliar to neuroradiologists and is rarely, if ever, discussed in radiology journals. The primary purpose of this review is to introduce the MRI-defined VD construct to the neuroradiology community. Case reports are highlighted in order to illustrate the profile of VD in terms of radiological, clinical, and neuropsychological findings. A secondary purpose is to elucidate and elaborate on the measurement of cerebrovascular disease through visual rating scales and semi- and fully-automated volumetric methods. These methods are crucial for determining whether lesion burden or lesion severity is the dominant pathological contributor to VD. Additionally, these rating methods have implications for the growing field of computer assisted diagnosis. Since VD has been found to have a profile that is distinct from other types of late-life depression, neuroradiologists, in conjunction with psychiatrists and psychologists, should consider VD in diagnosis and treatment planning.
Two Deletion Alleles in the C. elegans mir-49 gene.

Figure 1: (A) A schematic of the mir-49 locus and the location of the newly generated mir-49(zen99) and mir-49(zen102) deletion alleles. (B) zen99 removes 56 base pairs from the mir-49 precursor. (C) zen102 removes 58 base pairs from the mir-49 precursor.
Prevalence and stability of insomnia from preschool to early adolescence: a prospective cohort study in Norway

Background There is limited knowledge about the prevalence and stability of insomnia defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM). We therefore provide such estimates from preschool to early adolescence and explore potential sex differences. Methods We followed a representative community sample (n=1037) biennially from 4 to 14 years of age (2007–2017). Insomnia diagnoses and symptoms were captured by a semistructured clinical interview of parents and children (from age 8 years). Results At ages 4 and 6 years approximately 2.5% of children met the criteria for insomnia, whereas at ages 8, 10, 12 and 14 years the prevalence ranged from 7.5% to 12.3%. During the 10-year period examined nearly 1 in 5 children had insomnia at least once (18.7%). Sex differences were apparent with DSM-IV, but not DSM-5, criteria: boys (8.1%) had more insomnia than girls (4.5%) did at ages 4–10 years, whereas girls (11.4%) had more insomnia than boys (7.1%) did at ages 12 and 14 years. Insomnia proved stable, with 22.9%–40.1% of children retaining their diagnosis 2 years later. Having current insomnia produced medium to large ORs of between 5.1 (95% CI 2.6 to 9.8) and 15.3 (95% CI 4.4 to 52.9) for subsequent insomnia 2 years later compared with not having preceding insomnia. Conclusions Insomnia was less prevalent than previous research indicates, with nearly 1 in 5 participants having insomnia at least once between the ages of 4 and 14 years. Female preponderance emerged in early adolescence. Having insomnia at one time point was a considerable risk for subsequent insomnia, indicating that insomnia is persistent and warrants clinical attention.
Two new CRISPR-generated alleles in the C. elegans mir-1022 gene.

Figure 1: Using CRISPR/Cas9, two mir-1022 deletions/insertions (indels), zen97 and zen98, were generated. (A) A schematic of the C. elegans mir-1022 locus. The location of zen97 and zen98 deletions are designated by the blue and yellow rectangle, respectively. (B) The genetic sequence of the zen97 and zen98 deletions' endpoints in the mir-1022 locus, with the deletions represented by the ellipsis. Insertion sequence within each allele is in brackets. Description MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression during animal development. Large scale efforts to identify functions of individual miRNAs or miRNA families provide invaluable insight into the roles these miRNAs play in organism development (Miska et al. 2007, Alvarez-Saavedra and Horvitz 2010), however, some miRNA genes lack deletion alleles. To our knowledge, no alleles in C. elegans mir-1022 gene are currently available. Using CRISPR/Cas9 genome editing technique, we generated two novel alleles in the mir-1022 locus in C. elegans (Fig 1A). The zen97 allele is a 498 pair deletion of the mir-1022 locus which also inserts GAGGGGATT into that locus (Fig 1B). The zen98 allele is a 508 base pair deletion from the mir-1022 locus, inserting CGGTGTACAATGTATACAATGT in that location (Fig 1B). To specifically target the mir-1022 locus for editing, we used the following guide RNAs: mir-1022_gRNA 1: 5’TCGGGCCAACACATTTCAG-3′ and mir-1022_gRNA 2: 5’-TTTGCGTGCGAAAGTGGTGA-3′. The primers used for PCR genotyping were mir-1022.for3: 5’-CTAGTGCATTGTCCAGGCAG-3′ and mir-1022.rev3: 5’CGTGATCTCTTGGTGCACAT-3’. The Co-CRISPR marker dpy-10 was used in order to more easily identify worms with active CRISPR/Cas9 as previously described (Arribere et al. 2014). CRISPR components were injected into N2 animals as an RNP complex (Paix et al. 2015). Alt-R Cas9 (cat# 1081058), mir-1022 and dpy-10 Alt-R® CRISPR-Cas9 crRNAs (custom), and tracer RNA (cat# 1072532) were purchased from IDT. PCR screening identified two independent mutations, each disrupting the mir-1022 locus (Fig 1), which were subsequently homozygosed and sequenced. UY262 mir-1022(zen97) did not segregate any dumpy, dumpy roller, or roller animals and was not outcrossed. mir-1022(zen98) was outcrossed once to wild type (N2) males to remove a background dpy-10 mutation, generating the 1x outcrossed UY286 mir-1022(zen98) strain. Sequencing was repeated to confirm the mutation. Both alleles are homozygous viable. While not extensively characterized, no gross morphological phenotype was produced by either mir-1022 allele. Further phenotypic analysis will be necessary to determine the exact effect of the two mir-1022 mutations.
Fatal Retroperitoneal Hematoma in a Patient Receiving Enoxaparin for Bilateral Pulmonary Emboli

Venous thromboembolism occurs when a deep vein thrombosis travels to the lungs and forms a pulmonary embolism. Low-molecular-weight heparins are a mainstay in the treatment and prevention of venous thromboembolism and should be initiated promptly due to substantial morbidity and mortality. A rare side effect of low-molecular-weight heparins is major bleeding, which also carries a significant morbidity and mortality rate. Here, we present a case of a fatal retroperitoneal hematoma in a patient being treated with enoxaparin for bilateral pulmonary emboli.
Herbaria macroalgae as a proxy for historical upwelling trends in Central California

Planning for future ocean conditions requires historical data to establish more informed ecological baselines. To date, this process has been largely limited to instrument records and observations that begin around 1950. Here, we show how marine macroalgae specimens from herbaria repositories may document long-term ecosystem processes and extend historical information records into the nineteenth century. We tested the effect of drying and pressing six macroalgae species on amino acid, heavy metal and bulk stable isotope values over 1 year using modern and archived paper. We found historical paper composition did not consistently affect values. Certain species, however, had higher variability in particular metrics while others were more consistent. Multiple herbaria provided Gelidium (Rhodophyta) samples collected in southern Monterey Bay from 1878 to 2018. We examined environmental relationships and found δ15N correlated with the Bakun upwelling index, the productivity regime of this ecosystem, from 1946 to 2018. Then, we hindcasted the Bakun index using its derived relationship with Gelidium δ15N from 1878 to 1945. This hindcast provided new information, observing an upwelling decrease mid-century leading up to the well-known sardine fishery crash. Our case study suggests marine macroalgae from herbaria are an underused resource of the marine environment that precedes modern scientific data streams.
Ecological regime shift preserved in the Anthropocene stratigraphic record

Palaeoecological data are unique historical archives that extend back far beyond the last several decades of ecological observations. However, the fossil record of continental shelves has been perceived as too coarse (with centennial-millennial resolution) and incomplete to detect processes occurring at yearly or decadal scales relevant to ecology and conservation. Here, we show that the youngest (Anthropocene) fossil record on the northern Adriatic continental shelf provides decadal-scale resolution that accurately documents an abrupt ecological change affecting benthic communities during the twentieth century. The magnitude and the duration of the twentieth century shift in body size of the bivalve Corbula gibba is unprecedented given that regional populations of this species were dominated by small-size classes throughout the Holocene. The shift coincided with compositional changes in benthic assemblages, driven by an increase from approximately 25% to approximately 70% in median per-assemblage abundance of C. gibba. This regime shift increase occurred preferentially at sites that experienced at least one hypoxic event per decade in the twentieth century. Larger size and higher abundance of C. gibba probably reflect ecological release as it coincides with an increase in the frequency of seasonal hypoxia that triggered mass mortality of competitors and predators. Higher frequency of hypoxic events is coupled with a decline in the depth of intense sediment mixing by burrowing benthic organisms from several decimetres to less than 20 cm, significantly improving the stratigraphic resolution of the Anthropocene fossil record and making it possible to detect sub-centennial ecological changes on continental shelves.
Thermal Plasticity of the Kelp Laminaria digitata (Phaeophyceae) Across Life Cycle Stages Reveals the Importance of Cold Seasons for Marine Forests

Phenotypic plasticity (genotype × environment interaction) is an especially important means for sessile organisms to cope with environmental variation. While kelps, the globally most productive group of seaweeds, generally possess a wide thermal performance range, kelp populations at their warm distribution limits are threatened by ocean warming. Here, we investigated effects of temperature during ontogeny of the kelp Laminaria digitata across haploid gametophyte and diploid sporophyte life cycle stages in five distinct genetic lines. We hypothesized that thermal plasticity increases trait performance of juvenile sporophytes in experimental temperatures that match the temperature experienced during gametogenesis and recruitment, and that plasticity differs among genetic lines (genetic variation for plasticity). We applied a full-factorial experimental design to generate different temperature histories by applying 5 and 15°C during meiospore germination, gametogenesis of parental gametophytes and recruitment of offspring sporophytes (19–26 days), and juvenile sporophyte rearing (91–122 days). We then tested for thermal plasticity among temperature history treatments at 5 and 15°C in a final 12-day experiment assessing growth, the storage compound mannitol, carbon and nitrogen contents, and fluorometric responses in 3–4 month old sporophytes for five genetic lines. Our study provides evidence for the importance of cold temperatures at early development on later sporophyte performance of L. digitata. Gametogenesis and recruitment at 5°C promoted higher growth of offspring sporophytes across experimental temperatures. While photosynthetic capacity was higher at 15°C, carbon and nitrogen storage were higher at 5°C, both showing fast acclimation responses. We identified an important role of genetic variation for plasticity in shaping L. digitata’s thermal plasticity. Trait performance at 5 or 15°C (reaction norm slopes) differed among genetic lines, even showing opposite response patterns. Interestingly, genetic variation for plasticity was only significant when sporophytes were reared at 5°C. Thus, we provide evidence that the cold-temperate to Arctic kelp species, L. digitata, which possesses a wide temperature tolerance between 0 and 23°C, is impaired by warm temperature during gametogenesis and recruitment, reducing growth of juvenile sporophytes and expression of variable thermal plasticity in the wild.
Processing Facial Expressions That Conflict With Their Meanings to an Observer: An Event Related Potential Study

As social signals, identical facial expressions can be perceived differently, even oppositely, depending on the circumstances. Fast and accurate understanding of the information conveyed by others’ facial expressions is crucial for successful social interaction. In the current study, we used electroencephalographic analysis of several event-related potentials (ERPs) to investigate how the brain processes the facial expressions of others when they indicate different self-outcomes. In half of the trial blocks, a happy face indicated “Win” and an angry face indicated “Lose. ” In the other half of the blocks, the rule was reversed. The results showed that the N170 could distinguish expression valence and the N300 could distinguish outcome valence. The valence of the expression (happy or angry) and the valence of the outcome (Win or Loss) interacted with each other in the early, automatic perceptual processing stage (N1) as well as in the later, cognitive evaluation stage (P300). Standardized Low-Resolution Electromagnetic Tomography (sLORETA) results indicated that the N1 modulation only occurred for happy faces, which may relate to automatic emotion regulation, while the interaction on P300 was significant only for angry faces, which might be associated with the regulation of negative emotions.
Whole Genome Sequencing and Characterization of Multidrug-Resistant (MDR) Bacterial Strains Isolated From a Norwegian University Campus Pond

The presence of extended-spectrum β-lactamase (ESBL)-producing bacteria in environmental sources has been reported worldwide and constitutes a serious risk of community-acquired infections with limited treatment options. The current study aimed to explore the presence of these worrisome bacteria in a pond located at the Norwegian University of Life Sciences in Ås, Norway. A total of 98 bacterial isolates survived growth on selective chromogenic media and were identified by 16S rRNA Sanger sequencing. All strains were evaluated for the presence of the most commonly found β-lactamases and ESBLs in clinical settings (blaCTX–M groups 1, 2, and 9, blaCMY, blaSHV, and blaTEM) and carbapenemases (blaIMP, blaKPC, blaNDM, blaOXA, blaSFC1, blaVIM) through multiplex PCR. A total of eight strains were determined to contain one or more genes of interest. Phenotypic resistance to 18 antimicrobial agents was assessed and isolates were subjected to whole genome sequencing through a combination of Oxford Nanopore’s MinION and Illumina’s MiSeq. Results revealed the presence of β-lactamase and ESBL-producing Escherichia coli, Klebsiella pneumoniae, Stenotrophomonas maltophilia, and a Paraburkholderia spp. Identified β-lactamases and ESBLs include blaCTX–M, blaTEM, blaCMY, blaSHV and a possible blaKPC-like gene, with both documented and novel sequences established. In addition, two inducible β-lactamases were found, a class A β-lactamase (L1) and a cephalosporinase (L2). All strains were determined to be multidrug resistant and numerous resistance genes to non-β-lactams were observed. In conclusion, this study demonstrates that environmental sources are a potential reservoir of clinically relevant ESBL-producing bacteria that may pose a health risk to humans upon exposure.
Germline and Somatic Pharmacogenomics to Refine Rectal Cancer Patients Selection for Neo-Adjuvant Chemoradiotherapy

Neoadjuvant chemoradiotherapy (nCRT) followed by radical surgery is the standard of care for patients with Locally Advanced Rectal Cancer (LARC). Current selection for nCRT is based on clinical criteria regardless of any molecular marker. Pharmacogenomics may be a useful strategy to personalize and optimize nCRT in LARC. This review aims to summarize the most recent and relevant findings about the role of germline and somatic pharmacogenomics in the prediction of nCRT outcome in patients with LARC, discussing the state of the art of their application in the clinical practice. A systematic literature search of the PubMed database was completed to identify relevant English-language papers published up to January 2020. The chemotherapeutic backbone of nCRT is represented by fluoropyrimidines, mainly metabolized by DPD (Dihydro-Pyrimidine Dehydrogenase, DPYD). The clinical impact of testing DPYD*2A, DPYD*13, c.2846A > T and c.1236G > A-HapB3 before a fluoropyrimidines administration to increase treatment safety is widely acknowledged. Other relevant target genes are TYMS (Thymidylate Synthase) and MTHFR (Methylene-Tetrahydro-Folate Reductase), whose polymorphisms were mainly studied as potential markers of treatment efficacy in LARC. A pivotal role of a TYMS polymorphism in the gene promoter region (rs34743033) was reported and was pioneeringly used to guide nCRT treatment in a phase II study. The pharmacogenomic analysis of other pathways mostly involved in the cellular response to radiation damage, as the DNA repair and the activation of the inflammatory cascade, provided less consistent results. A high rate of somatic mutation in genes belonging to PI3K (Phosphatidyl-Inositol 3-Kinase) and MAPK (Mitogen-Activated Protein Kinase) pathways, as BRAF (V-raf murine sarcoma viral oncogene homolog B1), KRAS (Kirsten Rat Sarcoma viral oncogene homolog), NRAS (Neuroblastoma RAS viral (v-ras) oncogene homolog), PIK3CA (Phosphatidyl-Inositol-4,5-bisphosphate 3-Kinase, Catalytic Subunit Alpha), as well as TP53 (Tumor Protein 53) was reported in LARC. Their pharmacogenomic role, already defined in colorectal cancer, is under investigation in LARC with promising results concerning specific somatic mutations in KRAS and TP53, as predictors of tumor response and prognosis. The availability of circulating tumor DNA in plasma may also represent an opportunity to monitor somatic mutations in course of therapy.
Imaging Features of Sclerosing Epithelioid Fibrosarcoma of the Pancreas: A Case Report

Background: Sclerosing epithelioid fibrosarcoma (SEF) is an extremely rare fibrosarcoma variant. There is no complete imaging data on SEF involving the pancreas. Herein we report the computed tomography (CT) and magnetic resonance imaging (MRI) data of a patient with SEF that primarily involved the pancreas. Case Presentation: A 64-year-old man was found to have a solid mass in the tail of the pancreas on unenhanced CT. He had no constitutional symptoms. Contrast-enhanced abdominal CT and MRI were performed, and the results of the latter provided the diagnosis of a pancreatic neuroendocrine tumor. Laparoscopic distal pancreatectomy and splenectomy were performed. Anatomopathological examination and immunohistochemistry confirmed that the tumor was a SEF of the pancreas. The patient had no signs of recurrence or metastasis during a 12-months follow-up. Conclusion: We report an extremely rare case of SEF in the pancreas and its characterization with CT and MRI.
Case Report: Use of Amniotic Microvesicles for Regenerative Medicine Treatment of a Mare With Chronic Endometritis

Chronic endometritis is an inflammation in the inner layer of uterine mucosa, with or without an infectious process, which affects the animal's fertility but not its general health. A variety of treatments has been adopted over the years but to date, no effective cures have been able to renew the injured tissue. Since the defects in the fetal-maternal communication are caused by degenerative changes due to chronic endometrial inflammation, our working hypothesis was a new approach to this disease by the regenerative medicine using amniotic derived microvesicles (MVs) for their anti-inflammatory and regenerative effects. The MVs are responsible for horizontal transfer of genetic materials, including microRNA (miRNAs) that are involved in paracrine communication between origin cells and target cells. Thus, intrauterine MV infusion may be beneficial in degenerative chronic endometritis and in the fetal–maternal talk. The selected mare was an 11-year-old Friesian, with a history of failed pregnancies despite numerous insemination attempts. Punctual and evident heats characterized the reproductive history, but no insemination attempts had been made for many years. The first (failed) insemination was when the mare was 9-years-old. In the next two reproductive seasons, other attempts were made at regular intervals but none was successful. After a final insemination attempt using a stallion of proven fertility, the collection of an 8-day old embryo suggested that the mare was affected by implantation failure related to endometritis. The mare was treated with two cycles of intrauterine administration of amniotic-derived MVs. The success of the intrauterine administration of MVs was demonstrated by an improvement in the classification of endometritis and in a successful artificial insemination (AI) with implantation of an embryo, as detected at day 14 and with a pregnancy that is still ongoing. Probably, MVs were able to restore the injured endometrium and re-establish the proper communication for a successful embryo implantation.