Secondary (additional) findings from the 100,000 Genomes Project: Disease manifestation, health care outcomes, and costs of disclosure.

PURPOSE: The UK 100,000 Genomes Project offered participants screening for additional findings (AFs) in genes associated with familial hypercholesterolemia (FH) or hereditary cancer syndromes including breast/ovarian cancer (HBOC), Lynch, familial adenomatous polyposis, MYH-associated polyposis, multiple endocrine neoplasia (MEN), and von Hippel-Lindau. Here, we report disclosure processes, manifestation of AF-related disease, outcomes, and costs. METHODS: An observational study in an area representing one-fifth of England. RESULTS: Data were collected from 89 adult AF recipients. At disclosure, among 57 recipients of a cancer-predisposition-associated AF and 32 recipients of an FH-associated AF, 35% and 88%, respectively, had personal and/or family history evidence of AF-related disease. During post-disclosure investigations, 4 cancer-AF recipients had evidence of disease, including 1 medullary thyroid cancer. Six women with an HBOC AF, 3 women with a Lynch syndrome AF, and 2 individuals with a MEN AF elected for risk-reducing surgery. New hyperlipidemia diagnoses were made in 6 FH-AF recipients and treatment (re-)initiated for 7 with prior hyperlipidemia. Generating and disclosing AFs in this region cost £1.4m; £8680 per clinically significant AF. CONCLUSION: Generation and disclosure of AFs identifies individuals with and without personal or familial evidence of disease and prompts appropriate clinical interventions. Results can inform policy toward secondary findings.

Repeated surgical resections for management of high-grade glioma and its impact on quality of life.

PURPOSE: High-grade gliomas (HGG) are aggressive cancers, and their recurrence is inevitable, despite advances in treatment options. While repeated tumor resection has been shown to increase survival rate, its impact on quality of life is not clearly defined. To address this gap, we compared quality of life (QoL) changes in HGG patients who underwent first-time (FTR) versus repeat surgical resections (RSR) for management of recurrence. METHODS: Forty-four adults with HGG who underwent tumor resection were included in this study and classified into either the FTR group (n = 23) or the RSR group (n = 21). All patients completed comprehensive neuropsychological evaluations that included the Functional Assessment of Cancer Therapy-General (FACT-G) and Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) scales, pre-operatively and at two weeks post-operatively. RESULTS: There was no difference between the FTR and RSR groups in any of the QoL indices (all p > .05), except for improved emotional well-being and worsened social well-being, suggesting minimal detrimental effects of repeat surgeries on QoL in comparison to first time surgery. CONCLUSIONS: These results suggest that repeated resection is a viable strategy in certain cases for management of HGG recurrence, with similar impact on QoL as observed in patients undergoing first time surgery. These encouraging outcomes provide useful insight to guide treatment strategies and patient and clinician decision making to optimize surgical and functional outcomes.

Performance of intraoperative neurocognitive tests during awake surgery for patients with diffuse low-grade glioma.

Despite great advancements and the diffusion of awake surgery for brain tumors, the literature shows that the tests applied during the procedure are heterogeneous and non-standardized. This prospective, observational, descriptive study collected data on intraoperative brain mapping and the performance of multiple neurocognitive tests in 51 awake surgeries for diffuse low-grade glioma. Frequency of use and rate of intraoperative findings of different neurocognitive tests were analyzed. Patients mean age at the time of surgery was 35.1 (20-57) years. We performed 26 (51.0%) surgeries on the left hemisphere (LH) and 25 (49.0%) on the right hemisphere (RH). Significant differences were observed between the total number of functional findings (cortical and subcortical) identified in the LH and RH (p = 0.004). In subcortical findings alone, the differences remained significant (p = 0.0004). The RH subcortical region showed the lowest number of intraoperative findings, and this was correlated with functional outcome: Karnofsky performance scale at five days (p = 0.022), three months (p = 0.002) and one year (p = 0.002) post-surgery. On average, more tests were used to map the RH, with a lower frequency of both cortical and subcortical functional findings. Even though subcortical findings were less frequent than cortical findings, they were crucial to defining the resection margins. Based on the intraoperative findings, frequency of use, and rate of findings per use of the tests analyzed, the most relevant tests for each hemisphere for awake brain mapping were identified.

Estimating and planning hospital costs of public hospitals in Brazil.

While the estimate of hospital costs concerns the past, its planning focuses on the future. However, in many low and middle-income countries, public hospitals do not have robust accounting health systems to evaluate and project their expenses. In Brazil, public hospitals are funded based on government estimates of available hospital infrastructure, historical expenditures and population needs. However, these pieces of information are not always readily available for all hospitals. To solve this challenge, we propose a flexible simulation-based optimisation algorithm that integrates this dual task: estimating and planning hospital costs. The method was applied to a network of 17 public hospitals in Brazil to produce the estimates. Setting the model parameters for population needs and future hospital infrastructure can be used as a cost-projection tool for divestment, maintenance, or investment. Results show that the method can aid health managers in hospitals' global budgeting and policymakers in improving fairness in hospitals' financing.

Do Mesocarnivores Respond to the Seasonality in Management Practices in an Agroforestry Landscape?

In the Mediterranean, we find a mosaic of natural and cultural landscapes, where a variety of forest management practices created intermediate disturbance regimes that potentially increased biodiversity values. Nonetheless, it is essential to understand the species' long-term response to the dynamic management in agroecosystems, since the species tolerance to disturbance can change throughout the life cycle. Mammalian carnivores can be sensitive to human disturbance and are an essential part of ecosystems due to their regulatory and community structuring effects. We investigated the spatial response of five mesocarnivores species to spatially- and temporally- varying management practices in an agroforestry landscape. More specifically, we assessed the mesocarnivores' temporal changes in space use by implementing multi-season occupancy models in a Bayesian framework, using seasonal camera-trapping surveys for a 2-year period. All species had a weak response of local extinction to forestry management and livestock grazing pressure. For forest-dwelling species, occupancy was higher where productivity of perennial vegetation was high, while colonization between seasons was positively associated with vegetation cover. For habitat generalist species, we found that occupancy in the wet season increased with the distance to cattle exclusion plots. Most of these plots are pine stands which are subject to forestry interventions during winter. During the 2-year period we found seasonal fluctuations in occupancy for all species, with an overall slight decrease for three mesocarnivore species, while for the two forest-dwelling species there was an increase in occupancy between years. The weak species response to management practices supports the importance of traditional management for upholding a diverse mesocarnivore community in agroforestry systems but could also reflect these species' ecological plasticity and resilience to disturbance.

The mitogenomic landscape of Banisteriopsis caapi (Malpighiaceae), the sacred liana used for ayahuasca preparation.

The sacred ayahuasca brew, utilized by indigenous communities in the Amazon and syncretic religious groups in Brazil, primarily consists of a decoction of two plants: (i) the Amazonian liana known as Mariri or Jagube (Banisteriopsis caapi), and (ii) the shrub referred as Chacrona or Rainha (Psychotria viridis). While Chacrona leaves are rich in N,N-Dimethyltryptamine (DMT), a potent psychedelic, the macerated vine of Mariri provides beta-carboline alkaloids acting as monoamine oxidase inhibitors, preventing DMT's degradation. This study sequenced, assembled, and analyzed the complete genome of B. caapi's mitochondrion, yielding a circular structure spanning 503,502 bp. Although the mtDNA encompasses most plant mitochondrial genes, it lacks some ribosomal genes, presents some atypical genes, and contains plastid pseudogenes, suggesting gene transfer between organelles. The presence of a 7-Kb repetitive segment containing copies of the rrnL and trnfM genes suggests mitogenome isomerization, supporting the hypothesis of dynamic mitogenome maintenance in plants. Phylogenetics and phylogenomics across 24 Malpighiales confirms the sample's placement in the "Tucunacá" ethnovariety, aligning with morphological identification. This study spearheads efforts to decode the genome of this esteemed Malpighiaceae.

Spontaneous rhinorrhea and idiopathic intracranial hypertension: a complex and challenging association.

INTRODUCTION: Spontaneous CSF leak is a known complication of idiopathic intracranial hypertension (IIH). Patients with CSF rhinorrhea present a unique challenge within the IIH population, as the occurrence of a leak can mask the typical IIH symptoms and signs, complicating the diagnosis. Treatment of leaks in this population can also be challenging, with the risk of rhinorrhea recurrence if intracranial hypertension is not adequately treated. OBJECTIVE: The aim of this narrative review was to examine current literature on the association between spontaneous CSF rhinorrhea leaks and IIH, focusing on key clinical features, diagnostic approaches, management strategies, and outcomes. MATERIAL AND METHODS: A literature search was executed using the PubMed and Scopus databases. The search was confined to articles published between January 1985 and August 2023; extracted data was then analysed to form the foundation of the narrative review. RESULTS: This search yielded 26 articles, comprising 943 patients. Average age was 46.8 ± 6.5 years, and average body mass index was 35.8 ± 4.8. Most of the patients were female (74.33%). Presenting symptoms were rhinorrhea, headaches and meningitis. The most common imaging findings were empty sella and encephalocele. The standard treatment approach was endoscopic endonasal approach for correction of CSF rhinorrhea leak, and shunt placement was also performed in 128 (13%) patients. Recurrences were observed in 10% of cases. CONCLUSIONS: The complex relationship between spontaneous CSF leaks and IIH is a challenge that benefits from multidisciplinary evaluation and management for successful treatment. Treatments such as endoscopic repair, acetazolamide, and VP/ /LP shunts reduce complications and recurrence. Personalised plans addressing elevated intracranial pressure are crucial for successful outcomes.

Sustainable approach towards alternatives for the use of iron ore tailings in the construction sector using Data Envelopment Analysis methodology.

Iron ore tailings (IOTs) need to be properly managed to mitigate the environmental, social, and economic impacts of mining activities. To cope with this issue, we use data envelopment analysis (DEA) to evaluate alternatives for using IOT in the construction sector. The classical and weight restriction output-oriented DEA models were used in this analysis. The results show that the ranking of alternatives depends on the aspect being evaluated. Concrete block is the most environmentally friendly alternative when analysing both models. For both social and economic aspects, ceramics produced better results in the classical model, whereas Portland cement showed better outcomes in the weight restriction model. In this sense, the results suggest great potential for the use of IOT in the construction sector, enabling the reduction of risks and social and environmental impacts of tailings dams.

Enhancing metagenomic classification with compression-based features.

Metagenomics is a rapidly expanding field that uses next-generation sequencing technology to analyze the genetic makeup of environmental samples. However, accurately identifying the organisms in a metagenomic sample can be complex, and traditional reference-based methods may need to be more effective in some instances. In this study, we present a novel approach for metagenomic identification, using data compressors as a feature for taxonomic classification. By evaluating a comprehensive set of compressors, including both general-purpose and genomic-specific, we demonstrate the effectiveness of this method in accurately identifying organisms in metagenomic samples. The results indicate that using features from multiple compressors can help identify taxonomy. An overall accuracy of 95% was achieved using this method using an imbalanced dataset with classes with limited samples. The study also showed that the correlation between compression and classification is insignificant, highlighting the need for a multi-faceted approach to metagenomic identification. This approach offers a significant advancement in the field of metagenomics, providing a reference-less method for taxonomic identification that is both effective and efficient while revealing insights into the statistical and algorithmic nature of genomic data. The code to validate this study is publicly available at https://github.com/ieeta-pt/xgTaxonomy.

A Rare Case of Pulmonary Artery Sarcoma.

Pulmonary artery sarcoma (PAS) is a rare and aggressive mesenchymal tumor with an overall poor prognosis1-5. Due to similar clinical and radiologic findings, PAS is often misdiagnosed as a pulmonary embolism (PE) frequently leading to prolonged anticoagulation therapy, which delays the correct diagnosis 1-3. By presenting this clinical case our objective is to emphasize characteristic CT findings that favour a neoplastic origin of a pulmonary intravascular filling defect. PET-CT and MRI have also an important potential role in its diagnosis and therapeutical management.

A federated authentication schema among multiple identity providers.

Single Sign-On (SSO) methods are the primary solution to authenticate users across multiple web systems. These mechanisms streamline the authentication procedure by avoiding duplicate developments of authentication modules for each application. Besides, these mechanisms also provide convenience to the end-user by keeping the user authenticated when switching between different contexts. To ensure this cross-application authentication, SSO relies on an Identity Provider (IdP), which is commonly set up and managed by each institution that needs to enforce SSO internally. However, the solution is not so straightforward when several institutions need to cooperate in a unique ecosystem. This could be tackled by centralizing the authentication mechanisms in one of the involved entities, a solution raising responsibilities that may be difficult for peers to accept. Moreover, this solution is not appropriate for dynamic groups, where peers may join or leave frequently. In this paper, we propose an architecture that uses a trusted third-party service to authenticate multiple entities, ensuring the isolation of the user's attributes between this service and the institutional SSO systems. This architecture was validated in the EHDEN Portal, which includes web tools and services of this European health project, to establish a Federated Authentication schema.

A Chatbot-Like Platform to Enhance the Discovery of OMOP CDM Databases.

Multicentre studies become possible with the current strategies to solve the interoperability problems between databases. With the great adoption of those strategies, new problems regarding data discovery were raised. Some were solved using database catalogues and graphical dashboards for data analysis and comparison. However, when these communities grow, these strategies become obsolete. In this work, we addressed those challenges by proposing a platform with a chatbot-like mechanism to help medical researchers identify databases of interest. The tool was developed using the metadata extracted from OMOP CDM databases.

Sand smelt larvae's resilience to hypoxia and implications for thermal tolerance.

Deoxygenation is a growing threat to marine ecosystems, with an increase in the frequency, extent and intensity of hypoxia events in recent decades. These phenomena will pose various challenges to marine species, as it affects their survival, growth, body condition, metabolism and ability to handle other environmental stressors, such as temperature. Early life stages are particularly vulnerable to these changes. Thus, it is crucial to understand how these initial phases will respond to hypoxia to predict the impacts on marine populations and ecosystems. In this work, we aimed to evaluate the effect of oxygen (O2) availability on fitness related traits (mortality, growth and body condition), metabolism (Routine metabolic rates [RMR]) and thermal tolerance (CTmax), in early stages of Atherina presbyter, exposed for two weeks, to two O2 levels: normoxia (6.5-7.2 mg L-1) and hypoxia (2-2.5 mg L-1), through an experiment setup. Our findings showed that while low oxygen levels did not negatively impact mortality, total length, weight, or body condition (Fulton K), the larvae undergo metabolic depression when exposed to hypoxia, as an energy conservation mechanism. Furthermore, CTmax suffered a significant reduction in low O2 availability, due to the inability of the circulatory and respiratory systems to fulfill energy demands. These outcomes suggest that although early life stages of Atherina presbyter can survive under low oxygen environments, they are less capable of dealing with sudden increases in temperature when oxygen is scarce.

Electricity consumption dataset of a local energy cooperative.

Real-world data collections are generally not easily available. Energy measurements from buildings, houses and other devices can be used within different areas of research while being employed to plan or train models, allowing the improvement of power grid energy efficiency or providing more insight on how an energy community can work. This paper provides a dataset concerning a Portuguese community of 172 households that are geographically close to each other, enabling the establishment of relationships among buildings and the analysis of a community's power consumption. In addition to the consumed energy values, the related local weather information is included in the data. The intersection of weather data and energy measurements can be helpful to train AI models, contributing to explain variations in energy consumption and the absolute values of the energy readings. The inclusion of these weather parameters aims to unveil features that can correlate to the energy measurements, enabling them to be used in multiple areas of research. Hence, it will provide added value to the data as it can be reused to explore Machine Learning algorithms or community energy planning by grid operators.

Application of Thermomyces lanuginosus polygalacturonase produced in Komagataella phaffii in biomass hydrolysis and textile bioscouring.

In this work, the polygalacturonase (TL-PG1) from the thermophilic fungus Thermomyces lanuginosus was heterologously produced for the first time in the yeast Komagataella phaffii. The TL-PG1 was successfully expressed under the control of the AOX1 promoter and sequentially purified by His-tag affinity. The purified recombinant pectinase exhibited an activity of 462.6 U/mL toward polygalacturonic acid under optimal conditions (pH 6 and 55 ˚C) with a 2.83 mg/mL and 0.063 µmol/minute for Km and Vmax, respectively. When used as supplementation for biomass hydrolysis, TL-PG1 demonstrated synergy with the enzymatic cocktail Ctec3 to depolymerize orange citrus pulp, releasing 1.43 mg/mL of reducing sugar. In addition, TL-PG1 exhibited efficiency in fabric bioscouring, showing potential usage in the textile industry. Applying a protein dosage of 7 mg/mL, the time for the fabric to absorb water was 19.77 seconds (ten times faster than the control). Adding the surfactant Triton to the treatment allowed the reduction of the enzyme dosage by 50% and the water absorption time to 6.38 seconds. Altogether, this work describes a new versatile polygalacturonase from T. lanuginosus with the potential to be employed in the hydrolysis of lignocellulosic biomass and bioscouring.

Impact of symbiotic insect-specific viruses on mosquito vector competence for arboviruses.

Mosquitoes are vectors for arboviruses, such as dengue, Zika, and Chikungunya. Symbiotic interactions can affect the intrinsic ability of mosquitoes to acquire and transmit arboviruses, referred to as vector competence. Insect-specific viruses (ISVs) are commonly found in symbiotic associations with mosquitoes in the wild and can affect many aspects of mosquito biology. Here, we review current knowledge on the effects of symbiotic ISV-mosquito interactions on vector competence. We discuss potential mechanisms underlying these interactions and their implications for shaping new biological control strategies. Finally, we highlight the need for field data analyzing the circulation of ISVs in mosquitoes associated with mechanistic studies in the laboratory.

Towards discovery: an end-to-end system for uncovering novel biomedical relations.

Biomedical relation extraction is an ongoing challenge within the natural language processing community. Its application is important for understanding scientific biomedical literature, with many use cases, such as drug discovery, precision medicine, disease diagnosis, treatment optimization and biomedical knowledge graph construction. Therefore, the development of a tool capable of effectively addressing this task holds the potential to improve knowledge discovery by automating the extraction of relations from research manuscripts. The first track in the BioCreative VIII competition extended the scope of this challenge by introducing the detection of novel relations within the literature. This paper describes that our participation system initially focused on jointly extracting and classifying novel relations between biomedical entities. We then describe our subsequent advancement to an end-to-end model. Specifically, we enhanced our initial system by incorporating it into a cascading pipeline that includes a tagger and linker module. This integration enables the comprehensive extraction of relations and classification of their novelty directly from raw text. Our experiments yielded promising results, and our tagger module managed to attain state-of-the-art named entity recognition performance, with a micro F1-score of 90.24, while our end-to-end system achieved a competitive novelty F1-score of 24.59. The code to run our system is publicly available at https://github.com/ieeta-pt/BioNExt. Database URL: https://github.com/ieeta-pt/BioNExt.

Endoscopic Endonasal Transcavernous Hemipituitary Transposition for Resection of Invasive Prolactinoma: 2-Dimensional Operative Video.

Invasive prolactinomas often require multimodal management including medical and surgical interventions. Here, we present the case of a 34-year-old man with a history of progressive visual disturbances. MRI unveiled a sella lesion with suprasellar and retrosellar extensions. Elevated prolactin levels (6125 ng/mL) confirmed the diagnosis of prolactinoma, leading to initiation of medical treatment, with gradual escalation to maximum dosing. The patient achieved only partial hormonal response and incomplete improvement of symptoms, and therefore, surgical intervention was pursued with objective of maximum safe resection. The patient consented to the procedure. An endonasal endoscopic approach was selected. Surgical procedures encompassed transsellar, transtuberculum, and transplanum approaches, extended laterally to expose the right parasellar carotid and the anterior wall of the cavernous sinus. Subsequent steps involved opening the sellar and suprasellar dura mater, anterior wall of the cavernous sinus, and transcavernous hemipituitary transposition for access to the retrosellar region.1-5 Debulking of the lesion was performed, followed by dissection of the retrosellar space and resection of tumor component within the interpeduncular cistern. Reconstruction employed dura substitute and vascularized nasoseptal flap. Histopathology confirmed diagnosis of prolactinoma. Postoperative MRI findings and significantly improved prolactin levels (50 ng/mL) were compatible with near total resection. The patient's postoperative course was uneventful, resulting in discharge on the second postoperative day. The patient was additionally started on cabergoline 0.5 mg 2x/week to achieve hormonal control. This case demonstrates the application of surgical anatomy and its translation in modern surgical techniques that allow improved resection of such complex tumors while ensuring optimal clinical outcomes.

HL7 Fast Healthcare Interoperability Resources (HL7 FHIR) in digital healthcare ecosystems for chronic disease management: Scoping review.

BACKGROUND: The prevalence of chronic diseases has shifted the burden of disease from incidental acute inpatient admissions to long-term coordinated care across healthcare institutions and the patient's home. Digital healthcare ecosystems emerge to target increasing healthcare costs and invest in standard Application Programming Interfaces (API), such as HL7 Fast Healthcare Interoperability Resources (HL7 FHIR) for trusted data flows. OBJECTIVES: This scoping review assessed the role and impact of HL7 FHIR and associated Implementation Guides (IGs) in digital healthcare ecosystems focusing on chronic disease management. METHODS: To study trends and developments relevant to HL7 FHIR, a scoping review of the scientific and gray English literature from 2017 to 2023 was used. RESULTS: The selection of 93 of 524 scientific papers reviewed in English indicates that the popularity of HL7 FHIR as a robust technical interface standard for the health sector has been steadily rising since its inception in 2010, reaching a peak in 2021. Digital Health applications use HL7 FHIR in cancer (45 %), cardiovascular disease (CVD) (more than 15 %), and diabetes (almost 15 %). The scoping review revealed that references to HL7 FHIR IGs are limited to âˆ¼ 20 % of articles reviewed. HL7 FHIR R4 was most frequently referenced when the HL7 FHIR version was mentioned. In HL7 FHIR IGs registries and the internet, we found 35 HL7 FHIR IGs addressing chronic disease management, i.e., cancer (40 %), chronic disease management (25 %), and diabetes (20 %). HL7 FHIR IGs frequently complement the information in the article. CONCLUSIONS: HL7 FHIR matures with each revision of the standard as HL7 FHIR IGs are developed with validated data sets, common shared HL7 FHIR resources, and supporting tools. Referencing HL7 FHIR IGs cataloged in official registries and in scientific publications is recommended to advance data quality and facilitate mutual learning in growing digital healthcare ecosystems that nurture interoperability in digital health innovation.

Multi-head CRF classifier for biomedical multi-class named entity recognition on Spanish clinical notes.

The identification of medical concepts from clinical narratives has a large interest in the biomedical scientific community due to its importance in treatment improvements or drug development research. Biomedical named entity recognition (NER) in clinical texts is crucial for automated information extraction, facilitating patient record analysis, drug development, and medical research. Traditional approaches often focus on single-class NER tasks, yet recent advancements emphasize the necessity of addressing multi-class scenarios, particularly in complex biomedical domains. This paper proposes a strategy to integrate a multi-head conditional random field (CRF) classifier for multi-class NER in Spanish clinical documents. Our methodology overcomes overlapping entity instances of different types, a common challenge in traditional NER methodologies, by using a multi-head CRF model. This architecture enhances computational efficiency and ensures scalability for multi-class NER tasks, maintaining high performance. By combining four diverse datasets, SympTEMIST, MedProcNER, DisTEMIST, and PharmaCoNER, we expand the scope of NER to encompass five classes: symptoms, procedures, diseases, chemicals, and proteins. To the best of our knowledge, these datasets combined create the largest Spanish multi-class dataset focusing on biomedical entity recognition and linking for clinical notes, which is important to train a biomedical model in Spanish. We also provide entity linking to the multi-lingual Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) vocabulary, with the eventual goal of performing biomedical relation extraction. Through experimentation and evaluation of Spanish clinical documents, our strategy provides competitive results against single-class NER models. For NER, our system achieves a combined micro-averaged F1-score of 78.73, with clinical mentions normalized to SNOMED CT with an end-to-end F1-score of 54.51. The code to run our system is publicly available at https://github.com/ieeta-pt/Multi-Head-CRF. Database URL: https://github.com/ieeta-pt/Multi-Head-CRF.