DNA mismatch and damage patterns revealed by single-molecule sequencing.

Mutations accumulate in the genome of every cell of the body throughout life, causing cancer and other diseases1,2. Most mutations begin as nucleotide mismatches or damage in one of the two strands of the DNA before becoming double-strand mutations if unrepaired or misrepaired3,4. However, current DNA-sequencing technologies cannot accurately resolve these initial single-strand events. Here we develop a single-molecule, long-read sequencing method (Hairpin Duplex Enhanced Fidelity sequencing (HiDEF-seq)) that achieves single-molecule fidelity for base substitutions when present in either one or both DNA strands. HiDEF-seq also detects cytosine deamination-a common type of DNA damage-with single-molecule fidelity. We profiled 134 samples from diverse tissues, including from individuals with cancer predisposition syndromes, and derive from them single-strand mismatch and damage signatures. We find correspondences between these single-strand signatures and known double-strand mutational signatures, which resolves the identity of the initiating lesions. Tumours deficient in both mismatch repair and replicative polymerase proofreading show distinct single-strand mismatch patterns compared to samples that are deficient in only polymerase proofreading. We also define a single-strand damage signature for APOBEC3A. In the mitochondrial genome, our findings support a mutagenic mechanism occurring primarily during replication. As double-strand DNA mutations are only the end point of the mutation process, our approach to detect the initiating single-strand events at single-molecule resolution will enable studies of how mutations arise in a variety of contexts, especially in cancer and ageing.

Monitoring Sensors for Urban Air Quality: The Case of the Municipality of Lisbon.

Air pollution is a global issue that impacts environmental inequalities, and air quality sensors can have a decisive role in city policymaking for future cities. Science and society are already aware that during the most challenging times of COVID-19, the levels of air pollution in cities decreased, especially during lockdowns, when road traffic was reduced. Several pollution parameters can be used to analyse cities' environmental challenges, and it is more pressing than ever to have city climate decisions supported by sensor data. We have applied a data science approach to understand the evolution of the levels of carbon monoxide, nitrogen dioxide, particulate matter 2.5, and particulate matter 10 between August 2021 and July 2022. The analysis of the air quality levels, captured for the first time via 80 monitoring stations distributed throughout the municipality of Lisbon, has allowed us to realize that nitrogen dioxide and particulate matter 10 exceed the levels that are recommended by the World Health Organization, thereby increasing the health risk for those who live and work in Lisbon. Supported by these findings, we propose a central role for air quality sensors for policymaking in future cities, taking as a case study the municipality of Lisbon, Portugal, which is among the European cities that recently proposed be climate-neutral and smart city by 2030.

A Low-Cost Multi-Purpose IoT Sensor for Biologging and Soundscape Activities.

The rapid expansion in miniaturization, usability, energy efficiency, and affordability of Internet of Things (IoT) sensors, integrated with innovations in smart capability, is greatly increasing opportunities in ground-level monitoring of ecosystems at a specific scale using sensor grids. Surrounding sound is a powerful data source for investigating urban and non-urban ecosystem health, and researchers commonly use robust but expensive passive sensors as monitoring equipment to capture it. This paper comprehensively describes the hardware behind our low-cost, small multipurpose prototype, capable of monitoring different environments (e.g., remote locations) with onboard processing power. The device consists of a printed circuit board, microprocessor, local memory, environmental sensor, microphones, optical sensors and LoRa (Long Range) communication systems. The device was successfully used in different use cases, from monitoring mosquitoes enhanced with optical sensors to ocean activities using a hydrophone.

A Data-Centric Analysis of the Impact of Non-Electric Data on the Performance of Load Disaggregation Algorithms.

Recent research on non-intrusive load monitoring, or load disaggregation, suggests that the performance of algorithms can be affected by factors beyond energy data. In particular, by incorporating non-electric data in load disaggregation analysis, such as building and consumer characteristics, the estimation accuracy of consumption data may be improved. However, this association has rarely been explored in the literature. This work proposes a data-centric methodology for measuring the effect of non-electric characteristics on load disaggregation performance. A real-world dataset is considered for evaluating the proposed methodology, using various appliances and sample rates. The methodology results indicate that the non-electric characteristics may have varying effects on the performances of different building appliances. Therefore, the proposed methodology can be relevant for complementing load disaggregation analysis.

Passive Wi-Fi monitoring in the wild: a long-term study across multiple location typologies.

In this paper, we present a systematic analysis of large-scale human mobility patterns obtained from a passive Wi-Fi tracking system, deployed across different location typologies. We have deployed a system to cover urban areas served by public transportation systems as well as very isolated and rural areas. Over 4 years, we collected 572 million data points from a total of 82 routers covering an area of 2.8 km2. In this paper we provide a systematic analysis of the data and discuss how our low-cost approach can be used to help communities and policymakers to make decisions to improve people's mobility at high temporal and spatial resolution by inferring presence characteristics against several sources of ground truth. Also, we present an automatic classification technique that can identify location types based on collected data.

How manipulation of playing area dimensions in ball possession games constrains physical effort and technical actions in under-11, under-15 and under-23 soccer players.

The aim of this study was to investigate the effects of playing area manipulation (20 × 15 m, 25 × 20 m and 30 × 25 m) on external workloads (total distance covered, distance covered while walking, running and sprinting, number of sprints, maximum sprint speed), internal load perceptions (rating of perceived exertion) and technical actions of passing (number of passes with dominant and non-dominant foot, and maximum passing speed) during 4v4 ball possession small-sided and conditioned games in under-11, under-15 and under-23 soccer players. Results showed higher values in the large playing area for under-11 in the distance covered in different speed zones, sprint number and RPE (all p <.001) for under-15 in sprints number (p <.01) and maximum sprint speed (p =.02), and for under-23 in both RPE and sprint numbers (p <.01). Although no significant differences were found on technical actions, it was still possible to notice some effects through pairwise comparison. High-intensity running was promoted on larger playing areas, where under-11 s were also able to perform more technical actions of passing. Opposite, under-23s were able to perform more passing on smaller playing areas, where under-11 s perceived the exercise more intense. The impact of different playing areas was reduced for the under-15.

WikiPathways: a multifaceted pathway database bridging metabolomics to other omics research.

WikiPathways (wikipathways.org) captures the collective knowledge represented in biological pathways. By providing a database in a curated, machine readable way, omics data analysis and visualization is enabled. WikiPathways and other pathway databases are used to analyze experimental data by research groups in many fields. Due to the open and collaborative nature of the WikiPathways platform, our content keeps growing and is getting more accurate, making WikiPathways a reliable and rich pathway database. Previously, however, the focus was primarily on genes and proteins, leaving many metabolites with only limited annotation. Recent curation efforts focused on improving the annotation of metabolism and metabolic pathways by associating unmapped metabolites with database identifiers and providing more detailed interaction knowledge. Here, we report the outcomes of the continued growth and curation efforts, such as a doubling of the number of annotated metabolite nodes in WikiPathways. Furthermore, we introduce an OpenAPI documentation of our web services and the FAIR (Findable, Accessible, Interoperable and Reusable) annotation of resources to increase the interoperability of the knowledge encoded in these pathways and experimental omics data. New search options, monthly downloads, more links to metabolite databases, and new portals make pathway knowledge more effortlessly accessible to individual researchers and research communities.

Combined genetic and epigenetic alterations of the TERT promoter affect clinical and biological behavior of bladder cancer.

In urothelial bladder cancer (UBC), risk stratification remains an important unmet need. Limitless self-renewal, governed by TERT expression and telomerase activation, is crucial for cancer progression. Thus, telomerase activation through the interplay of mutations (TERTpMut ) and epigenetic alterations in the TERT promoter may provide further insight into UBC behavior. Here, we investigated the combined effect of TERTpMut and the TERT Hypermethylated Oncological Region (THOR) status on telomerase activation and patient outcome in a UBC international cohort (n = 237). We verified that TERTpMut were frequent (76.8%) and present in all stages and grades of UBC. Hypermethylation of THOR was associated with higher TERT expression and higher-risk disease in nonmuscle invasive bladder cancers (NMIBC). TERTpMut alone predicted disease recurrence (HR: 3.18, 95%CI 1.84 to 5.51, p < 0.0001) but not progression in NMIBC. Combined THORhigh /TERTpMut increased the risk of disease recurrence (HR 5.12, p < 0.0001) and progression (HR 3.92, p = 0.025). Increased THOR hypermethylation doubled the risk of stage progression of both TERTpwt and TERTpMut NMIBC. These results highlight that both mechanisms are common and coexist in bladder cancer and while TERTpMut is an early event in bladder carcinogenesis THOR hypermethylation is a dynamic process that contributes to disease progression. While the absence of alterations comprises an extremely indolent phenotype, the combined genetic and epigenetic alterations of TERT bring additional prognostic value in NMIBC and provide a novel insight into telomere biology in cancer.

Psychological and Psychosocial Interventions for Depression and Anxiety in Patients With Age-Related Macular Degeneration: A Systematic Review.

OBJECTIVE: To review the current literature on psychosocial and psychological interventions to prevent and treat depression and anxiety in patients with age-related macular degeneration (AMD). METHODS: The authors conducted a systematic review of literature evaluating psychosocial and psychological interventions for depression and anxiety in patients with AMD. Primary searches of PubMed, Cochrane library, EMBASE, Global Health, Web of Science, EBSCO, and Science Direct were conducted to include all articles published up to April 21, 2018. RESULTS: Of a total of 398 citations retrieved, the authors selected 12 eligible studies published between 2002 and 2016. The authors found nine randomized controlled trials (RCT), and three non-randomized intervention (NRI) studies. RCT studies suggested that interventions using group self-management techniques and individual behavioral activation plus low vision rehabilitation can be effective to treat and prevent depression in patients with AMD, and one study suggested that a stepped-care intervention using cognitive-behavioral techniques can be effective to manage anxiety and depression over time. NRI studies highlighted a positive effect of self-help and emotion-focused interventions to reduce depression. CONCLUSION: Clinical practice with patients with AMD can rely on some tailored cognitive-behavioral therapeutic protocols to improve patients' mental health, but further clinical trials will generate the necessary evidence-based knowledge to improve those therapeutic techniques and offer additional tailored interventions for patients with AMD.

Anaplastic astrocytoma with piloid features, a novel molecular class of IDH wildtype glioma with recurrent MAPK pathway, CDKN2A/B and ATRX alterations.

Tumors with histological features of pilocytic astrocytoma (PA), but with increased mitotic activity and additional high-grade features (particularly microvascular proliferation and palisading necrosis) have often been designated anaplastic pilocytic astrocytomas. The status of these tumors as a separate entity has not yet been conclusively demonstrated and molecular features have only been partially characterized. We performed DNA methylation profiling of 102 histologically defined anaplastic pilocytic astrocytomas. T-distributed stochastic neighbor-embedding (t-SNE) and hierarchical clustering analysis of these 102 cases against 158 reference cases from 12 glioma reference classes revealed that a subset of 83 of these tumors share a common DNA methylation profile that is distinct from the reference classes. These 83 tumors were thus denominated DNA methylation class anaplastic astrocytoma with piloid features (MC AAP). The 19 remaining tumors were distributed amongst the reference classes, with additional testing confirming the molecular diagnosis in most cases. Median age of patients with MC AAP was 41.5 years. The most frequent localization was the posterior fossa (74%). Deletions of CDKN2A/B (66/83, 80%), MAPK pathway gene alterations (49/65, 75%, most frequently affecting NF1, followed by BRAF and FGFR1) and mutations of ATRX or loss of ATRX expression (33/74, 45%) were the most common molecular alterations. All tumors were IDH1/2 wildtype. The MGMT promoter was methylated in 38/83 tumors (45%). Outcome analysis confirmed an unfavorable clinical course in comparison to PA, but better than IDH wildtype glioblastoma. In conclusion, we show that a subset of histologically defined anaplastic pilocytic astrocytomas forms a separate DNA methylation cluster, harbors recurrent alterations in MAPK pathway genes in combination with alterations of CDKN2A/B and ATRX, affects patients who are on average older than those diagnosed with PA and has an intermediate clinical outcome.

WikiPathways: capturing the full diversity of pathway knowledge.

WikiPathways (http://www.wikipathways.org) is an open, collaborative platform for capturing and disseminating models of biological pathways for data visualization and analysis. Since our last NAR update, 4 years ago, WikiPathways has experienced massive growth in content, which continues to be contributed by hundreds of individuals each year. New aspects of the diversity and depth of the collected pathways are described from the perspective of researchers interested in using pathway information in their studies. We provide updates on extensions and services to support pathway analysis and visualization via popular standalone tools, i.e. PathVisio and Cytoscape, web applications and common programming environments. We introduce the Quick Edit feature for pathway authors and curators, in addition to new means of publishing pathways and maintaining custom pathway collections to serve specific research topics and communities. In addition to the latest milestones in our pathway collection and curation effort, we also highlight the latest means to access the content as publishable figures, as standard data files, and as linked data, including bulk and programmatic access.

Marital adjustment in the context of female breast cancer: A systematic review.

OBJECTIVE: Breast cancer (BC) diagnosis and subsequent treatments present significant challenges and distress for both patients and their partners. This can lead to difficulties in marital relationships and, consequently, decreases in marital adjustment and psychosocial adaptation to BC for both partners. Our objective was to systematically review studies assessing marital adjustment in the context of female BC to understand which factors are associated with marital adjustment in both patients and partners and characterize the measures used to assess marital adjustment within these studies. METHODS: This systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. English, peer-reviewed articles exploring factors associated with marital adjustment in the context of female BC were considered for inclusion. RESULTS: Fourteen studies were included. Results evidenced that psychosocial variables play an important role on marital adjustment. Specifically, open and constructive communication, more social support, and supportive dyadic coping were found to be associated with higher levels of marital adjustment. Other variables such as self-efficacy, sexual functioning, and psychological adjustment were also positively associated with marital adjustment. CONCLUSIONS: Most studies evidenced an association between psychosocial variables and marital adjustment for both women and their partners. Some important dimensions such as communication patterns, coping strategies, and social support dynamics were identified as potential targets for psychological interventions. Some variables, however, were explored only in a few studies, which limit our conclusions. Future studies should explore the role these variables and other relational and emotional variables play in promoting marital adjustment after BC.

PathVisio 3: an extendable pathway analysis toolbox.

PathVisio is a commonly used pathway editor, visualization and analysis software. Biological pathways have been used by biologists for many years to describe the detailed steps in biological processes. Those powerful, visual representations help researchers to better understand, share and discuss knowledge. Since the first publication of PathVisio in 2008, the original paper was cited more than 170 times and PathVisio was used in many different biological studies. As an online editor PathVisio is also integrated in the community curated pathway database WikiPathways. Here we present the third version of PathVisio with the newest additions and improvements of the application. The core features of PathVisio are pathway drawing, advanced data visualization and pathway statistics. Additionally, PathVisio 3 introduces a new powerful extension systems that allows other developers to contribute additional functionality in form of plugins without changing the core application. PathVisio can be downloaded from http://www.pathvisio.org and in 2014 PathVisio 3 has been downloaded over 5,500 times. There are already more than 15 plugins available in the central plugin repository. PathVisio is a freely available, open-source tool published under the Apache 2.0 license (http://www.apache.org/licenses/LICENSE-2.0). It is implemented in Java and thus runs on all major operating systems. The code repository is available at http://svn.bigcat.unimaas.nl/pathvisio. The support mailing list for users is available on https://groups.google.com/forum/#!forum/wikipathways-discuss and for developers on https://groups.google.com/forum/#!forum/wikipathways-devel.

A functional human Poly(A) site requires only a potent DSE and an A-rich upstream sequence.

We have analysed the sequences required for cleavage and polyadenylation in the intronless melanocortin 4 receptor (MC4R) pre-mRNA. Unlike other intronless genes, 3'end processing of the MC4R primary transcript is independent of any auxiliary sequence elements and only requires the core poly(A) sequences. Mutation of the AUUAAA hexamer had little effect on MC4R 3'end processing but small changes in the short DSE severely reduced cleavage efficiency. The MC4R poly(A) site requires only the DSE and an A-rich upstream sequence to direct efficient cleavage and polyadenylation. Our observation may be highly relevant for the understanding of how human noncanonical poly(A) sites are recognised. This is supported by a genome-wide analysis of over 10 000 poly(A) sites where we show that many human noncanonical poly(A) signals contain A-rich upstream sequences and tend to have a higher frequency of U and GU nucleotides in their DSE compared with canonical poly(A) signals. The importance of A-rich elements for noncanonical poly(A) site recognition was confirmed by mutational analysis of the human JUNB gene, which contains an A-rich noncanonical poly(A) signal.

Optimal 2D audio features estimation for a lightweight application in mosquitoes species: Ecoacoustics detection and classification purposes.

Mosquitoes are the vector of diseases that kill more than one million people per year worldwide. Surveillance systems are essential for understanding their complex ecology and behaviour. This is fundamental for predicting disease risk caused by mosquitoes and formulating effective control strategies against mosquito-borne diseases such as malaria, dengue, and Zika. Mosquito populations vary heterogeneously in urban and rural landscapes, fluctuating with seasonal and climatic trends and human activity. Several approaches provide environmental data for mosquito mapping and risk prediction. However, they rely traditionally upon labour-intensive techniques such as manual traps. This paper presents the optimal audio features for mosquito identification using ecoacoustics signals to automatically identify different mosquito species from their wingbeat sounds based on popular audio features. The audio selection method uses Density-Based Spatial Clustering of Applications with Noise (DBSCAN) and Silhouette coefficient to evaluate the clusters in the data through the optimal-combined audio features. To classify the mosquito species and distinguish them from environmental-urban noise, the method comprises the Gaussian Mixture Model (GMM) and Gibbs approach for Aedes aegypti, and Culex quinquefasciatus, using the acoustic recordings of their wingbeat signals. Finally, comparing GMM and Gibbs, the two have very similar accuracy, but the classification time is much faster for Gibbs sampling, making it a good candidate for a lightweight solution. These are essential when deploying the described models to monitor mosquito vectors in the wild with Internet of Things (IoT) technologies.

Using passive Wi-Fi for community crowd sensing during the COVID-19 pandemic.

Sensing passersby and detecting crowded locations is a growing area of research and development in the last decades. The COVID-19 pandemic compelled authorities and public and private institutions to monitor access and occupancy of crowded spaces. This work addresses the detection of crowds in points of interest (POI) by using a territory grid analysis categorizing POIs by the services available in each location and comparing data gathered from a community passive Wi-Fi infrastructure against mobile cellular tower association data from telecom companies. In Madeira islands (Portugal), we used data from the telecom provider NOS for the timespan of 4 months as ground truth and found a strong correlation with sparse passive Wi-Fi. An official regional mobile application shows the occupancy data to end-users based on the territory categorization and the passive Wi-Fi infrastructure in POIs. Occupancy data shows historical hourly trends of each location, and the real-time occupation, helping visitors and locals plan their commutes better to avoid crowded spaces.

Cepstral Measures in the Fado Voice: Gender, Age and Phonatory Tasks.

Cepstral measures are sensitive to gender, age and phonatory tasks. With a cepstral measure designated as the CPP, it was possible to confirm the vulnerability of the Fado singers' voice. These were established at the vocal pathological threshold, which suggests a need for a direct clinical approach for these voice users. OBJECTIVES/HYPOTHESIS: This study aimed to characterize cepstral peak prominence (CPP) and cepstral peak prominence smoothed (CPPS) in the Fado singing voice and to determine if there were significant differences in CPP and CPPS measures between spoken and sung tasks, as well as due to singers' gender and age. METHODS: Forty seven males and 57 females Fado singers, ranging from 18 to 70 years participated in this study. Spoken voice tasks were sustained [a] and reading aloud the phonetically balanced text "O Sol". Sung tasks were sustained [a] of the word [ɐfinaÉ«] and the Fado chorus song "Nem às paredes confesso". Acoustic measures included CPP and CPPS. CPP was measured using Analyses of Dysphonia in Speech and Voice software, of Multi-Speech program, Model 3700, by KayPENTAX. CPPS was measured using Praat software (4.2.1/2003). Statistical analysis was performed with an IBM SPSS Statistics version 22 program. CPP and CPPS mean differences of spoken and sung tasks were analyzed using paired samples t-test, with α at .05. RESULTS: CPP and CPPS values of singers' voice changed according to the gender, age and phonatory tasks. There were significant differences between CPP and CPPS measures (P < 0.05). Generally, young male singers, in their sung task, presented the highest CPP and CPPS values. The highest CPP mean was obtained by older males in sustained spoken [a] and the lowest was obtained by younger males in their reading aloud task. For CPPS, the highest mean value was obtained by younger males during sung [a] and the lowest was by younger males in the reading aloud task. CONCLUSION: Males presented higher cepstral measures than females. Young singers presented higher cepstral measures than older. Sung tasks had higher cepstral measures than spoken tasks. CPPS means are overall higher than CPP means. This study reinforces the need for a clinical prevention approach directed at potential vocal disorders in Fado singers.