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Counterfactual thinking (reflecting on \"what might have been\") has been shown to enhance future performance by translating information about past mistakes into plans for future action. Prefactual thinking (imagining \"what might be if…\") may serve a greater preparative function than counterfactual thinking as it is future-orientated and focuses on more controllable features, thus providing a practical script to prime future behaviour. However, whether or not this difference in hypothetical thought content may translate into a difference in actual task performance has been largely unexamined. In Experiment 1 (n = 42), participants performed trials of a computer-simulated physical task, in between which they engaged in either task-related hypothetical thinking (counterfactual or prefactual) or an unrelated filler task (control). As hypothesised, prefactuals contained more controllable features than counterfactuals. Moreover, participants who engaged in either form of hypothetical thinking improved significantly in task performance over trials compared to participants in the control group. The difference in thought content between counterfactuals and prefactuals, however, did not yield a significant difference in performance improvement. Experiment 2 (n = 42) replicated these findings in a dynamic balance task environment. Together, these findings provide further evidence for the preparatory function of counterfactuals, and demonstrate that prefactuals share this same functional characteristic.

Bacteria in the genus Gallaecimonas are known for their ability to breakdown complex hydrocarbons, making them of particular ecological and biotechnological significance. However, few species have been isolated to date, and their ecological distribution has yet to be examined. Here, we report a novel strain of G. pentaromativorans , designated as strain 10A, which was isolated from a Pacific oyster ( Magallana gigas , a.k.a. Crassostrea gigas ) collected from a farm experiencing a mass mortality event in British Columbia (BC), Canada. Gallaecimonas pentaromativorans strain 10A is a rod-shaped, motile bacterium and has a circular genome of 4,322,156 bp encoding 3,928 protein-coding sequences (CDS). Phylogenetic analysis showed that strain 10A is closely related to members of G. pentaromativorans. Like other Gallaecimonas members, strain 10A is predicted to harbor specific pathways involved in degrading xenobiotic compounds including polycyclic aromatic hydrocarbons (PAHs), producing biosurfactants, and assimilating nitrate and sulfate; however, it is uniquely equipped with an additional 166 genes belonging to 147 protein families, including a putative higB - higA that likely contributes to enhanced stress response. Strain 10A also possesses Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) and CRISPR-associated (Cas) system (CRISPR-Cas), prevalent in Gallaecimonas (detected in three out of four species), implying a potential defense mechanism against exogenous mobile genetic elements such as plasmids and viruses. We also mined publicly available databases to establish the widespread distribution of bacteria in the genus Gallaecimonas in seawater, sediments, and freshwater across latitude, suggesting its versatility and importance to environmental processes. Ultimately, this study demonstrates that the genome of G. pentaromativorans strain 10A, isolated from a Pacific oyster, may encode a suite of putative functions, including xenobiotic breakdown, biosurfactant production, and CRISPR-Cas defense. This plasticity and breadth in metabolic function help to explain the cosmopolitan distribution of members of this genus.

The role of oral microbiota in head and neck squamous cell carcinoma (HNSCC) is poorly understood. Here we sought to evaluate the association of the bacterial microbiome with host gene methylation and patient outcomes, and to explore its potential as a biomarker for early detection or intervention. Here we performed 16S rRNA gene amplicon sequencing in sixty-eight HNSCC patients across both tissue and oral rinse samples to identify oral bacteria with differential abundance between HNSCC and controls. A subset of thirty-one pairs of HNSCC tumor tissues and the adjacent normal tissues were characterized for host gene methylation profile using bisulfite capture sequencing. We observed significant enrichments of Fusobacterium and Peptostreptococcus in HNSCC tumor tissues when compared to the adjacent normal tissues, and in HNSCC oral rinses when compared to healthy subjects, while ten other bacterial genera were largely depleted. These HNSCC-related bacteria were discriminative for HNSCC and controls with area under the receiver operating curves (AUCs) of 0.84 and 0.86 in tissue and oral rinse samples, respectively. Moreover, Fusobacterium nucleatum abundance in HNSCC cases was strongly associated with non-smokers, lower tumor stage, lower rate of recurrence, and improved disease-specific survival. An integrative analysis identified that enrichment of F. nucleatum was associated with host gene promoter methylation, including hypermethylation of tumor suppressor genes LXN and SMARCA2, for which gene expressions were downregulated in the HNSCC cohort from The Cancer Genome Atlas. In conclusion, we identified a taxonomically defined microbial consortium associated with HNSCC that may have clinical potential regarding biomarkers for early detection or intervention. Host–microbe interactions between F. nucleatum enrichment and clinical outcomes or host gene methylation imply a potential role of F. nucleatum as a pro-inflammatory driver in initiating HNSCC without traditional risk factors, which warrants further investigation for the underlying mechanisms.

Practical adherence barriers (e.g., medication frequency) are generally more amenable to intervention than perceptual barriers (e.g., beliefs). Measures which assess adherence barriers exist, however these tend to measure a mix of factors. There is a need to identify what practical barriers are captured by current measures. To identify and synthesise the practical adherence barriers which are assessed by currently available self- or observer-report adherence measures. A search for systematic reviews of self- or observer-report report adherence measures was conducted. Three electronic databases (Embase, Ovid Medline, and PsycInfo) were searched using terms based on adherence, adherence barriers and measures. Systematic reviews reporting on adherence measures which included at least one self- or observer-report questionnaire or scale were included. Adherence measures were extracted and coded on whether they addressed perceptual or practical barriers, or both. Practical items were then analysed thematically. Following screening of 272 initial abstracts, 20 full-text papers were reviewed. Four were excluded after full-text review, leaving 16 systematic reviews for data extraction. From these, 187 different adherence measures were extracted and coded, and 23 unique measures were identified as assessing practical barriers and included in the final analysis. Seven key themes were identified: formulation; instructions for use; issues with remembering; capability-knowledge and skills; financial; medication supply and social environment. Existing adherence measures capture a variety of practical barriers which can be grouped into seven categories. These findings may be used to inform the development of a measure of practical adherence barriers.

Electronic adherence monitoring (EAM) is increasingly used to improve adherence. However, there is limited evidence on the effect of EAM in across chronic conditions and on patient acceptability. We aimed to assess the effect of EAM on adherence and clinical outcomes, across all ages and all chronic conditions, and examine acceptability in this systematic review and meta-analysis. A systematic search of Ovid MEDLINE, EMBASE, Social Work Abstracts, PsycINFO, International Pharmaceutical Abstracts and CINAHL databases was performed from database inception to December 31, 2020. Randomised controlled trials (RCTs) that evaluated the effect of EAM on medication adherence as part of an adherence intervention in chronic conditions were included. Study characteristics, differences in adherence and clinical outcomes between intervention and control were extracted from each study. Estimates were pooled using random-effects meta-analysis, and presented as mean differences, standardised mean differences (SMD) or risk ratios depending on the data. Differences by study-level characteristics were estimated using subgroup meta-analysis to identify intervention characteristics associated with improved adherence. Effects on adherence and clinical outcomes which could not be meta-analysed, and patient acceptability, were synthesised narratively. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline was followed, and Risk of bias (RoB) assessed using the Cochrane Collaboration's RoB tool for RCTs. The review is registered with PROSPERO CRD42017084231. Our search identified 365 studies, of which 47 studies involving 6194 patients were included. Data from 27 studies (n = 2584) were extracted for the adherence outcome. The intervention group (n = 1267) had significantly better adherence compared to control (n = 1317), (SMD = 0.93, CI:0.69 to 1.17, p<0.0001) with high heterogeneity across studies (I2 = 86%). There was a significant difference in effect according to intervention complexity (p = 0.01); EAM only improved adherence when used with a reminder and/or health provider support. Clinical outcomes were measured in 38/47 (81%) of studies; of these data from 14 studies were included in a meta-analysis of clinical outcomes for HIV, hypertension and asthma. In total, 13/47 (28%) studies assessed acceptability; patient perceptions were mixed. Patients receiving an EAM intervention had significantly better adherence than those who did not, but improved adherence did not consistently translate into clinical benefits. Acceptability data were mixed. Further research measuring effects on clinical outcomes and patient acceptability are needed.

DEK::AFF2 fusion-associated papillary squamous cell carcinoma is a novel entity characterized by its unique translocation and malignant clinical course. In this study, AFF immunohistochemistry (IHC) was performed in recurrent sinonasal papillomas for reviewing the prevalence of undiagnosed DEK::AFF2 carcinomas and to investigate the performance of AFF IHC in diagnosis of DEK::AFF2 carcinomas. Recurrent sinonasal papillomas after surgical excision in a two-decade period were retrieved. Histologic slides were reviewed for features of DEK::AFF2 carcinoma. AFF IHC was performed, and cases with any (> 1%) nuclear positivity were validated by DEK break apart fluorescence in situ hybridization. Totally 43 cases were included, comprising 28 inverted, 6 exophytic, one oncocytic, and 8 non-specified sinonasal papillomas. Five (11.6%) cases exhibited positivity to AFF IHC. Three cases exhibited patchy weak to moderate staining intensity predominantly in a granular cytoplasmic pattern. Two cases exhibited strong and diffuse (> 90%) nuclear staining. Cases showing weak staining were negative for DEK rearrangement, while those with strong staining were positive. Both cases of DEK::AFF2 carcinoma showed aggressive behavior with extensive local invasion and nodal metastasis. Background stromal plasma cells, when present, consistently showed strong and diffuse staining. AFF IHC was further performed in plasmacytoma samples as control and showed strong and diffuse immunoreactivity. A significant minority of recurrent sinonasal papillomas represent DEK::AFF2 carcinomas. Granular, cytoplasmic, or incomplete AFF staining should be considered as negative. In view of the rarity of DEK::AFF2 carcinomas, plasma cells and plasma cell neoplasms are potential for internal and surrogate external controls.

In this paper we report an initial validation of the Shape Trail Test-Child Version (STT-CV) with a non-clinical sample of children aged 6 to 9 years. The STT-CV has been developed as an age-appropriate and culturally fair direct downward extension of the Trail Making Test (TMT) for the assessment of cognitive flexibility. Children completed the STT-CV and four established measures of executive functions that assessed working memory, inhibitory control and task switching. Results showed the expected age-based differences in completion times for both parts of the STT-CV (Trail A and Trail B). Children's performance on the STT-CV correlated significantly with all four measures of executive functions. After controlling for the effects of chronological age, completion times for Trail B remained correlated with most other measures of executive functions. These findings provide emerging evidence for the utility of the STT-CV, and highlight the need for designing and using appropriate variants of the TMT in the behavioural assessment of cognitive flexibility in developmentally and culturally diverse populations.

Ferroptosis is a non-apoptotic form of regulated cell death caused by the failure of the glutathione-dependent lipid-peroxide-scavenging network. FINO2 is an endoperoxide-containing 1,2-dioxolane that can initiate ferroptosis selectively in engineered cancer cells. We investigated the mechanism and structural features necessary for ferroptosis initiation by FINO2. We found that FINO2 requires both an endoperoxide moiety and a nearby hydroxyl head group to initiate ferroptosis. In contrast to previously described ferroptosis inducers, FINO2 does not inhibit system xc– or directly target the reducing enzyme GPX4, as do erastin and RSL3, respectively, nor does it deplete GPX4 protein, as does FIN56. Instead, FINO2 both indirectly inhibits GPX4 enzymatic function and directly oxidizes iron, ultimately causing widespread lipid peroxidation. These findings suggest that endoperoxides such as FINO2 can initiate a multipronged mechanism of ferroptosis.

[This corrects the article DOI: 10.1371/journal.pone.0168181.].