An interconnected data infrastructure to support large-scale rare disease research.

The Solve-RD project brings together clinicians, scientists, and patient representatives from 51 institutes spanning 15 countries to collaborate on genetically diagnosing ("solving") rare diseases (RDs). The project aims to significantly increase the diagnostic success rate by co-analyzing data from thousands of RD cases, including phenotypes, pedigrees, exome/genome sequencing, and multiomics data. Here we report on the data infrastructure devised and created to support this co-analysis.

Interrogation of a fluoropolymer dispersion manufactured with a non-fluorinated polymerization aid for targeted and non-targeted fluorinated residuals by liquid chromatography high resolution mass spectrometry.

Recent advances in fluoropolymer polymerization have focused on replacing perfluorinated polymerization aids (PAs) with hydrocarbon-based alternatives. Hydrocarbon PAs are vulnerable to fluorinated radicals during polymerization, leading to the creation of hundreds of process-specific polyfluorinated residuals. These residuals, which include low molecular weight extractable or leachable impurities, are challenging to detect at trace levels.

Serial Postoperative Circulating Tumor DNA Assessment Has Strong Prognostic Value During Long-Term Follow-Up in Patients With Breast Cancer.

Purpose: Here, we report the sensitivity of a personalized, tumor-informed circulating tumor DNA (ctDNA) assay (Signatera) for detection of molecular relapse during long-term follow-up of patients with breast cancer.

Methods: A total of 156 patients with primary breast cancer were monitored clinically for up to 12 years after surgery and adjuvant chemotherapy. Semiannual blood samples were prospectively collected, and analyzed retrospectively to detect residual disease by ultradeep sequencing using ctDNA assays, developed from primary tumor whole-exome sequencing data.

Meta-Analysis of Circulating Tumor Cell PD-L1 Expression and the Association with Clinical Outcomes in Non-Small Cell Lung Cancer.

Background: Programmed death ligand-1 (PD-L1) expression on circulating tumor cells (CTCs) has been suggested to provide prognostic information in non-small cell lung cancer (NSCLC), but consensus relative to treatment outcomes is lacking. We conducted the first comprehensive meta-analysis exploring its potential as a prognostic and predictive marker, and assessed the concordance between PD-L1 + CTCs and paired tumor tissue in NSCLC patients.

Method: A comprehensive search was applied to PubMed and EMBASE to identify 26 studies that evaluated PD-L1 + CTCs and their association with survival outcomes in 1236 NSCLC patients.

Restricting social networking site use for one week produces varied effects on mood but does not increase explicit or implicit desires to use SNSs: Findings from an ecological momentary assessment study.

Recent research on the addictive potential of modern technologies such as the internet, smartphones, or social networking sites (SNSs) has suggested that emotional and motivational changes associated with the sudden discontinuation of engagement with the technology mirror the aversive consequences seen when drug use is ceased abruptly. This has been observed even in moderate users and interpreted as a manifestation of withdrawal, an important marker of physical dependence in substance use disorders. On the other hand, a growing literature emphasises the positive effects of "digital detox" on mental health and well-being.

Correction: Wadsley, M.; Ihssen, N. A Systematic Review of Structural and Functional MRI Studies Investigating Social Networking Site Use. 2023, , 787.

During the final proofreading step of this paper [...

A Systematic Review of Structural and Functional MRI Studies Investigating Social Networking Site Use.

An understanding of the neurocognitive profile underlying the use of social networking sites (SNSs) can help inform decisions about the classification of problematic SNS use as an addictive disorder and elucidate how/when 'SNS addiction' might develop. The present review aimed to synthesize structural and functional MRI research investigating problematic/compulsive forms of SNS use or regular (non-addicted) SNS use behaviours. We conducted a systematic search for research articles published in English using the , , and databases up to October 2022.

A Rapid, Shallow Whole Genome Sequencing Workflow Applicable to Limiting Amounts of Cell-Free DNA.

Background: Somatic copy number alterations (sCNAs) acquired during the evolution of breast cancer provide valuable prognostic and therapeutic information. Here we present a workflow for screening sCNAs using picogram amounts of cell-free DNA (cfDNA) and single circulating tumor cells (CTCs).

Methods: We repurposed the Ion ReproSeq PGS™ preimplantation genetic testing kit to perform shallow whole genome sequencing on 178 cfDNA samples (300 pg) and individual CTCs from 10 MBC patients with metastatic breast cancer (MBC) recovered by CellSearch®/DEPArray™.

The roles of implicit approach motivation and explicit reward in excessive and problematic use of social networking sites.

Despite growing concerns about the addictive potential of social networking sites (SNSs), little is known about the precise neural, cognitive, and emotional processes underpinning compulsive SNS behaviours, such as excessive checking of SNSs. Recent evidence points to the important role of reward in SNS behaviours and one avenue to examine reward processes related to SNSs is the use of behavioural paradigms that allow for the measurement of implicit motivational responses, such as the approach avoidance task (AAT). The AAT has been successfully utilised to capture changes in unconscious reward processes in substance use disorders and other behavioural addictions, with faster approach reactions to addiction-related stimuli reflecting increased wanting/urges to have/consume the reward.

The loci of Stroop effects: a critical review of methods and evidence for levels of processing contributing to color-word Stroop effects and the implications for the loci of attentional selection.

Despite instructions to ignore the irrelevant word in the Stroop task, it robustly influences the time it takes to identify the color, leading to performance decrements (interference) or enhancements (facilitation). The present review addresses two questions: (1) What levels of processing contribute to Stroop effects; and (2) Where does attentional selection occur? The methods that are used in the Stroop literature to measure the candidate varieties of interference and facilitation are critically evaluated and the processing levels that contribute to Stroop effects are discussed. It is concluded that the literature does not provide clear evidence for a distinction between conflicting and facilitating representations at phonological, semantic and response levels (together referred to as informational conflict), because the methods do not currently permit their isolated measurement.

The Predictive Utility of Reward-Based Motives Underlying Excessive and Problematic Social Networking Site Use.

Compulsive seeking of reward is a hallmark feature of drug addiction, but the role of reward is less well understood in behavioural addictions. The present study investigated the predictive utility of ten reward-based motives, which we identified in the literature, in explaining excessive and problematic use of social networking sites (SNSs). These motives were examined in a cross-sectional survey of 411 young adults, revealing that prolonged use and excessive checking were predicted by distinctly different motives.

The effect of high-frequency rTMS of the left dorsolateral prefrontal cortex on the resolution of response, semantic and task conflict in the colour-word Stroop task.

Previous work investigating the effect of rTMS of left Dorso-Lateral Prefrontal Cortex (DLPFC) on Stroop task performance reports no changes to the Stroop effect but reduced reaction times on both congruent and incongruent trials relative to sham stimulation; an effect attributed to an enhanced attentional (or task) set for colour classification. The present study tested this account by investigating whether, relative to vertex stimulation, rTMS of the left DLPFC modifies task conflict, a form of conflict that arises when task sets for colour classification and word reading compete, given that this particular type of conflict would be reduced by an enhanced task set for colour classification. Furthermore, the present study included measures of other forms of conflict present in the Stroop task (response and semantic conflict), the potential effects on which would have been hidden in previous studies employing only incongruent and congruent stimuli.

A reward and incentive-sensitization perspective on compulsive use of social networking sites - Wanting but not liking predicts checking frequency and problematic use behavior.

The use of Social Networking Sites (SNSs) has exponentially increased over the past decade, leading to warnings about the addictive potential of this technology. Yet, the idea of SNS addiction remains controversial and more theory-driven research is required to understand the mechanisms of excessive and compulsive SNS use and to facilitate the development of targeted interventions helping affected users. In the present article we propose to utilize a reward-based approach to further our understanding of these behaviors.

Clinically Actionable Insights into Initial and Matched Recurrent Glioblastomas to Inform Novel Treatment Approaches.

Glioblastoma is the most common primary adult brain tumour, and despite optimal treatment, the median survival is 12-15 months. Patients with matched recurrent glioblastomas were investigated to try to find actionable mutations. Tumours were profiled using a validated DNA-based gene panel.

An fMRI Study of Response and Semantic Conflict in the Stroop Task.

An enduring question in selective attention research is whether we can successfully ignore an irrelevant stimulus and at what point in the stream of processing we are able to select the appropriate source of information. Using methods informed by recent research on the varieties of conflict in the Stroop task the present study provides evidence for specialized functions of regions of the frontoparietal network in processing response and semantic conflict during Stroop task performance. Specifically, we used trial types and orthogonal contrasts thought to better independently measure response and semantic conflict and we presented the trial types in pure blocks to maximize response conflict and therefore better distinguish between the conflict types.

Quality assurance of falls reduction in an orthopaedic ward using a novel bedside trolley table set-up strategy.

Objective: To assess whether a novel bedside trolley table set-up decreased inpatient falls (IF) postintervention.

Methods: From December 2012 to December 2014, geriatric patients admitted to our orthopaedic ward with extreme falls risk had a bedside trolley placed between them and a floor sensor mat to give responders more time to prevent IF. Pre- and postintervention falls data was reviewed for falls reduction using falls per month as comparison standard.

A mass spectrometry method for the determination of the species of origin of gelatine in foods and pharmaceutical products.

Gelatine is a component of a wide range of foods. It is manufactured as a by-product of the meat industry from bone and hide, mainly from bovine and porcine sources. Accurate food labelling enables consumers to make informed decisions about the food they buy.

Ancient proteins resolve the evolutionary history of Darwin's South American ungulates.

No large group of recently extinct placental mammals remains as evolutionarily cryptic as the approximately 280 genera grouped as 'South American native ungulates'. To Charles Darwin, who first collected their remains, they included perhaps the 'strangest animal[s] ever discovered'. Today, much like 180 years ago, it is no clearer whether they had one origin or several, arose before or after the Cretaceous/Palaeogene transition 66.

Characterisation of novel α-keratin peptide markers for species identification in keratinous tissues using mass spectrometry.

Rationale: In ancient and/or damaged artefacts containing keratinous materials, the species of origin of the materials can be difficult to identify through visual examination; therefore, a minimally destructive methodology for species identification is required. While hair fibres from some species have seen substantial characterisation, others such as horn or baleen have received little or no attention, or lack protein sequences allowing formal identification using proteomics techniques.

Methods: We used the PMF method (Peptide Mass Fingerprinting with matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF-MS)) to catalogue and identify diagnostic peptide markers up to the genus level.

QuEChERS multiresidue method validation and mass spectrometric assessment for the novel anthranilic diamide insecticides chlorantraniliprole and cyantraniliprole.

The gas-phase dissociation reactions of chlorantraniliprole (Rynaxypyr) and cyantraniliprole (Cyazypyr) have been studied in triple-quadrupole, ion trap, and orbitrap mass spectrometers equipped with electrospray and desorption electrospray ion sources, revealing the formation of odd-electron fragment ions, the structures of which were elucidated. The odd-electron fragments were unusually abundant, and their formation is proposed to occur via a tricyclic intermediate. The applicability of the QuEChERS multiresidue method for the quantitation of chlorantraniliprole and cyantraniliprole was also assessed in this study.