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.