Towards Interpretable Sleep Stage Classification Using Cross-Modal Transformers.

Accurate sleep stage classification is significant for sleep health assessment. In recent years, several machine-learning based sleep staging algorithms have been developed, and in particular, deep-learning based algorithms have achieved performance on par with human annotation. Despite improved performance, a limitation of most deep-learning based algorithms is their black-box behavior, which have limited their use in clinical settings. Here, we propose a cross-modal transformer, which is a transformer-based method for sleep stage classification. The proposed cross-modal transformer consists of a cross-modal transformer encoder architecture along with a multi-scale one-dimensional convolutional neural network for automatic representation learning. The performance of our method is on-par with the state-of-the-art methods and eliminates the black-box behavior of deep-learning models by utilizing the interpretability aspect of the attention modules. Furthermore, our method provides considerable reductions in the number of parameters and training time compared to the state-of-the-art methods. Our code is available at https://github.com/Jathurshan0330/Cross-Modal-Transformer. A demo of our work can be found at https://bit.ly/Cross_modal_transformer_demo.

Cordyceps cateniannulata: An endophyte of coffee, a parasite of coffee leaf rust and a pathogen of coffee pests.

Here, we report on a Cordyceps species entering into a multi-trophic, multi-kingdom association. Cordyceps cateniannulata, isolated from the stem of wild Coffea arabica in Ethiopia, is shown to function as an endophyte, a mycoparasite and an entomopathogen. A detailed polyphasic taxonomic study, including a multilocus phylogenetic analysis, confirmed its identity. An emended description of C. cateniannulata is provided herein. Previously, this species was known as a pathogen of various insect hosts in both the Old and New World. The endophytic status of C. cateniannulata was confirmed by re-isolating it from inoculated coffee plants. Inoculation studies have further shown that C. cateniannulata is a mycoparasite of Hemileia vastatrix, as well as an entomopathogen of major coffee pests; infecting and killing Hypothenemus hampei and Leucoptera coffeella. This is the first record of C. cateniannulata from Africa, as well as an endophyte and a mycoparasite. The implications for its use as a biocontrol agent are discussed.

Perceived Stress, but Not Rumination, Mediates the Relationship Between Trait Mindfulness and Sleep Quality in Young Adults.

Objective: Poor sleep among young adults is prevalent, yet the mediating variables are largely understudied, and there is limited relevant work utilizing objective sleep measures. The present study investigated the mediating effects of perceived stress and rumination in the relationship between trait mindfulness and subjective and objective sleep quality in young adults. Methods: A total of 170 healthy adults (aged 18-37, M = 20.8, SD = 2.9) self-reported on trait mindfulness, perceived stress, and rumination. The primary (N = 140) and secondary (N = 30) samples both completed the Pittsburgh Sleep Quality Index (PSQI) to assess subjective sleep quality. The secondary sample (N = 30) additionally provided sleep diaries, as well as wrist-worn actigraphy data for assessing objective sleep quality. A mediation analysis was conducted to assess the effect of trait mindfulness on sleep quality with perceived stress and rumination as mediators. Results: Trait mindfulness was positively associated with better subjective sleep quality; this was fully mediated by perceived stress, b = -0.08, 95% CI [-.12, -0.06]. Rumination was negatively associated with subjective sleep quality but did not mediate the relationship between trait mindfulness and sleep quality, b = -0.01, 95% CI [-.03, 0.02]. Only trait mindfulness was correlated with diary-based sleep ratings, and none of the measures were associated with actigraphy-based sleep quality. Conclusion: This study indicates that perceived stress is an important mediator in the relationship between trait mindfulness and subjective sleep quality among young adults, rather than rumination. These findings have implications for mindfulness-based therapeutic approaches to address the high prevalence of sleep disorders among young adults, adding mechanistic detail to the literature.

Training physicians in motivational communication: An integrated knowledge transfer study protocol.

OBJECTIVE: While behavior change counseling (BCC) targeting health risk behaviors has shown efficacy for improving patient health outcomes, barriers to knowledge translation have resulted in poor uptake among health care providers (HCPs). This article outlines the development of a new BCC training framework for HCPs, from inception to readiness for efficacy testing. It provides an example of integrated knowledge translation (iKT) used in alignment with the obesity-related behavioral intervention trials model. METHOD: (a) A modified Delphi process identified essential BCC skills for HCPs; (b) a survey assessed HCP attitudes and training needs; (c) an online competency assessment tool was developed using iKT mixed methods; (d) a training program was developed and refined using a logic model; and (e) the program was optimized using iterative rounds of participant feedback. A future proof-of-concept trial (f) will determine the program's readiness for full efficacy testing. RESULTS: A Delphi panel (n = 46) identified 11 core BCC competencies for HCPs, defining "motivational communication." The HCP survey (n = 80) showed willingness to devote 4 hr to introductory training in BCC. The Motivational Communication Competency Assessment Test (MC-CAT: an online, interactive evaluation tool) and a motivational communication training program (MOTIVATOR: accredited for continuing education by the Royal College of Physicians and Surgeons of Canada) were collaboratively developed with knowledge users. The optimization process (n = 11) provided key feedback, with minor changes being made to the program. CONCLUSIONS: In developing a new BCC framework, obstacles to BCC implementation were addressed through an iterative iKT process. This should improve eventual intervention uptake. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Probing perfection: The relentless art of meddling for pulmonary airway segmentation from HRCT via a human-AI collaboration based active learning method.

In the realm of pulmonary tracheal segmentation, the scarcity of annotated data stands as a prevalent pain point in most medical segmentation endeavors. Concurrently, most Deep Learning (DL) methodologies employed in this domain invariably grapple with other dual challenges: the inherent opacity of 'black box' models and the ongoing pursuit of performance enhancement. In response to these intertwined challenges, the core concept of our Human-Computer Interaction (HCI) based learning models (RS_UNet, LC_UNet, UUNet and WD_UNet) hinge on the versatile combination of diverse query strategies and an array of deep learning models. We train four HCI models based on the initial training dataset and sequentially repeat the following steps 1-4: (1) Query Strategy: Our proposed HCI models selects those samples which contribute the most additional representative information when labeled in each iteration of the query strategy (showing the names and sequence numbers of the samples to be annotated). Additionally, in this phase, the model selects the unlabeled samples with the greatest predictive disparity by calculating the Wasserstein Distance, Least Confidence, Entropy Sampling, and Random Sampling. (2) Central line correction: The selected samples in previous stage are then used for domain expert correction of the system-generated tracheal central lines in each training round. (3) Update training dataset: When domain experts are involved in each epoch of the DL model's training iterations, they update the training dataset with greater precision after each epoch, thereby enhancing the trustworthiness of the 'black box' DL model and improving the performance of models. (4) Model training: Proposed HCI model is trained using the updated training dataset and an enhanced version of existing UNet. Experimental results validate the effectiveness of this Human-Computer Interaction-based approaches, demonstrating that our proposed WD-UNet, LC-UNet, UUNet, RS-UNet achieve comparable or even superior performance than the state-of-the-art DL models, such as WD-UNet with only 15 %-35 % of the training data, leading to substantial reductions (65 %-85 % reduction of annotation effort) in physician annotation time.

The impact of insect herbivory on biogeochemical cycling in broadleaved forests varies with temperature.

Herbivorous insects alter biogeochemical cycling within forests, but the magnitude of these impacts, their global variation, and drivers of this variation remain poorly understood. To address this knowledge gap and help improve biogeochemical models, we established a global network of 74 plots within 40 mature, undisturbed broadleaved forests. We analyzed freshly senesced and green leaves for carbon, nitrogen, phosphorus and silica concentrations, foliar production and herbivory, and stand-level nutrient fluxes. We show more nutrient release by insect herbivores at non-outbreak levels in tropical forests than temperate and boreal forests, that these fluxes increase strongly with mean annual temperature, and that they exceed atmospheric deposition inputs in some localities. Thus, background levels of insect herbivory are sufficiently large to both alter ecosystem element cycling and influence terrestrial carbon cycling. Further, climate can affect interactions between natural populations of plants and herbivores with important consequences for global biogeochemical cycles across broadleaved forests.

Validation and clinical application of implantable loop recorders for diagnosis of atrial fibrillation in horses.

BACKGROUND: Paroxysmal atrial fibrillation (pAF) occurs sporadically and can impair athletic performance. Gold standard for diagnosis is surface electrocardiography (ECG), however, this requires AF to be sustained. Implantable loop recorders (ILRs) are routinely used for AF detection in human medicine. While ILR placement has been studied in horses, its AF detection performance is unknown. OBJECTIVES: (I) Validation of ILRs for AF detection in horses. (II) Determining pAF incidence using ILRs and estimate the positive predictive value (PPV). STUDY DESIGN: (I) Experimental study; (II) Longitudinal observational study. METHODS: (I) Implantation of ILRs in 15 horses with AF and 13 horses in sinus rhythm. Holter ECGs were recorded at: 1, 4, 8, 12 and 16 weeks of AF. The ILR ECGs were compared with surface ECGs to assess diagnostic sensitivity and specificity. (II) Eighty horses (43 Warmbloods, 37 Standardbreds) with ILRs were monitored for 367 days [IQR 208-621]. RESULTS: (I) ILRs detected AF on all recording days, in horses with AF, with a sensitivity of 66.1% (95% CI: 65.8-66.5) and a specificity of 99.99% (95% CI: 99.97-99.99). The sensitivity remained consistent across all time points. (II) The incidence of pAF was 6.3% (5/80). In horses with pAF, the PPV ranged from 8% to 87%. Increased body condition score (BCS > 6/9) was associated with an increased number of false positive episodes (p = 0.005). MAIN LIMITATIONS: (I) Horses were stabled during the ECG recordings, and AF was induced, rather than naturally occurring pAF. (II) Integrated algorithm in this ILR is optimised for AF detection in humans using remote monitors. Additionally, sensing is affected by motion artefacts. CONCLUSION: The ILR reliably detected AF in resting horses, particularly in horses with normal BCS (6/9). The ILR proved useful to detect pAF and is recommended alongside Holter monitoring for diagnostic workup of horses with suspected pAF.

Canine ovarian epithelial tumours: histopathological and immunohistochemical evaluation with proposed histopathological classification system.

Canine ovarian epithelial tumours (OETs) are currently divided into ovarian adenomas and carcinomas, which are further inconsistently subclassified as papillary or cystic, whereas in human medicine, OETs are subdivided into several subtypes. This study aimed to establish clear morphological features enabling more consistent distinction between benign OETs and ovarian carcinomas (OvCas) as well as defining different histopathological patterns of canine OvCas. Analysis revealed a mitotic count threshold of >2 as a potential criterion for differentiating OvCas from benign OETs. Alongside ovarian adenomas, ovarian borderline tumours were introduced as a distinct category among benign OETs. OvCas exhibited five different histopathological patterns, namely papillary, solid with tubular differentiation, micropapillary, cystic and sarcomatous. Since some OvCas can morphologically overlap with other ovarian tumours, the expression of cytokeratin 7, a cytokeratin expressed in ovarian epithelium, was assessed and proved helpful, although it was not expressed in all cases. Furthermore, we investigated the expression of 14-3-3σ and cyclooxygenase 2 (COX-2). Based on the frequent expression of 14-3-3σ, this marker appears to have a role in canine OETs since it is not expressed in normal canine ovaries. The infrequent expression of COX-2 suggests that it is a poor candidate as a potential therapeutic target in canine OvCas.

A force-sensitive mutation reveals a non-canonical role for dynein in anaphase progression.

The diverse roles of the dynein motor in shaping microtubule networks and cargo transport complicate in vivo analysis of its functions significantly. To address this issue, we have generated a series of missense mutations in Drosophila Dynein heavy chain. We show that mutations associated with human neurological disease cause a range of defects, including impaired cargo trafficking in neurons. We also describe a novel microtubule-binding domain mutation that specifically blocks the metaphase-anaphase transition during mitosis in the embryo. This effect is independent from dynein's canonical role in silencing the spindle assembly checkpoint. Optical trapping of purified dynein complexes reveals that this mutation only compromises motor performance under load, a finding rationalized by the results of all-atom molecular dynamics simulations. We propose that dynein has a novel function in anaphase progression that depends on it operating in a specific load regime. More broadly, our work illustrates how in vivo functions of motors can be dissected by manipulating their mechanical properties.

The enduring world forest carbon sink.

The uptake of carbon dioxide (CO2) by terrestrial ecosystems is critical for moderating climate change1. To provide a ground-based long-term assessment of the contribution of forests to terrestrial CO2 uptake, we synthesized in situ forest data from boreal, temperate and tropical biomes spanning three decades. We found that the carbon sink in global forests was steady, at 3.6 ± 0.4 Pg C yr-1 in the 1990s and 2000s, and 3.5 ± 0.4 Pg C yr-1 in the 2010s. Despite this global stability, our analysis revealed some major biome-level changes. Carbon sinks have increased in temperate (+30 ± 5%) and tropical regrowth (+29 ± 8%) forests owing to increases in forest area, but they decreased in boreal (-36 ± 6%) and tropical intact (-31 ± 7%) forests, as a result of intensified disturbances and losses in intact forest area, respectively. Mass-balance studies indicate that the global land carbon sink has increased2, implying an increase in the non-forest-land carbon sink. The global forest sink is equivalent to almost half of fossil-fuel emissions (7.8 ± 0.4 Pg C yr-1 in 1990-2019). However, two-thirds of the benefit from the sink has been negated by tropical deforestation (2.2 ± 0.5 Pg C yr-1 in 1990-2019). Although the global forest sink has endured undiminished for three decades, despite regional variations, it could be weakened by ageing forests, continuing deforestation and further intensification of disturbance regimes1. To protect the carbon sink, land management policies are needed to limit deforestation, promote forest restoration and improve timber-harvesting practices1,3.

Comparison of parent-reported motivators of non-vaccination for children 5-11 years old in Australia and Canada: Results of the iCARE study.

BACKGROUND: Despite COVID-19 infection being less severe in children compared to adults, vaccination for children from the age of 6 months onwards is recommended in many countries to reduce symptom severity and prevent severe disease. However, vaccination against COVID-19 for children remains controversial and uptake has been low. AIMS: To assess and compare the rate of change of parent-reported COVID-19 vaccine uptake in children aged 5 to 11 years and motivators of vaccine acceptance and non-vaccination among parents/guardians in Canada and Australia. METHODS: As part of the iCARE study, two cross-sectional representative samples in Canada and Australia were collected between May 20 and September 12, 2022 (i.e., 5 and 9 months after the COVID-19 vaccine rollout for children 5-11 years) using online panels. Parents/guardians reported the vaccine status of their children and motivators for vaccine acceptance and non-vaccination. General linear models were used to estimate differences between countries in terms of vaccine uptake and motivators across time. RESULTS: Parent-reported vaccine uptake for children 5-11 years didn't increase over the study period (T1 = 87 %,T2 = 86 %; OR = 0.83; 95 %CI = 0.45-1.54) and was overall lower in Canada (60.8 %) compared to Australia (71.6 %)(OR = 0.56; 95 %CI = 0.33-0.96). In both countries the socioeconomic characteristics of parents who didn't vaccinate their children were similar and having information on either the short- or long-term side effects of the vaccine were important motivators. However, vaccine effectiveness was more important in Canada and trust in the company that developed the vaccine and a recommendation from the child's doctor were more important motivators in Australia. CONCLUSION: Parent-reported vaccine uptake for children 5-11 years plateaued early in the vaccine rollout. The main motivators for parents of unvaccinated children varied between the two countries but information on vaccine safety and effectiveness were common to both countries. Findings may inform future tailored vaccine communication efforts and pandemic planning in Australia and Canada to optimize vaccine uptake for primary school children.

CD117 expression in canine ovarian tumours.

Canine ovarian cancer poses a significant diagnostic and therapeutic challenge. The heterogeneous nature of ovarian tumours makes accurate histological identification difficult, whilst treatment is limited to surgical excision. The tyrosine kinase receptor CD117 is neo-expressed in many tumours and represents a potential diagnostic and prognostic biomarker and therapeutic target. This study aimed to establish if CD117 is neoexpressed in canine ovarian tumours. Immunohistochemistry was employed to assess expression of CD117 in 29 canine ovarian tumour samples. CD117 labelling was assessed with a semiquantitative immunoreactivity score, and the location of labelling was recorded as membranous, focal cytoplasmic or diffuse cytoplasmic. Histological morphology was assessed and used to assign subgroups based on growth pattern. Cytokeratin 7 labelling was used to indicate the tumour type as epithelial or sex-cord stromal in origin. Mitotic index, percentage of necrosis and vascular invasion were also assessed and evaluated for association with CD117 expression. Overall, 81% of ovarian tumours neoexpressed CD117 and normal ovarian tissue did not express CD117. Positive immunolabelling was seen in a subset of cells in both ovarian carcinomas (n = 20) and ovarian granulosa cell tumours (n = 3). There was no association between CD117 expression and patient age, histological subtype, mitotic index, percentage of necrosis or vascular invasion. This is the largest study to identify the expression of CD117 in canine ovarian tumours, but further research is needed to elucidate its prognostic and therapeutic value.

Rural healthcare workforce preparation, response, and work during the COVID-19 pandemic in Australia: Lessons learned from in-depth interviews with rural health service leaders.

BACKGROUND: Low population density, geographic spread, limited infrastructure and higher costs are unique challenges in the delivery of healthcare in rural areas. During the COVID-19 pandemic, emergency powers adopted globally to slow the spread of transmission of the virus included population-wide lockdowns and restrictions upon movement, testing, contact tracing and vaccination programs. The aim of this research was to document the experiences of rural health service leaders as they prepared for the emergency pandemic response, and to derive from this the lessons learned for workforce preparedness to inform recommendations for future policy and emergency planning. METHODOLOGY AND METHODS: Interviews were conducted with leaders from two rural public health services in Australia, one small (500 staff) and one large (3000 staff). Data were inductively coded and analysed thematically. PARTICIPANTS: Thirty-three participants included health service leaders in executive, clinical, and administrative roles. FINDINGS: Six major themes were identified: Working towards a common goal, Delivery of care, Education and training, Organizational governance and leadership, Personal and psychological impacts, and Working with the Local Community. Findings informed the development of a applied framework. CONCLUSION: The study findings emphasise the critical importance of leadership, teamwork and community engagement in preparing the emergency pandemic response in rural areas. Informed by this research, recommendations were made to guide future rural pandemic emergency responses or health crises around the world.

Electrocatalytic Formal C(sp2)-H Alkylations via Nickel-Catalyzed Cross-Electrophile Coupling with Versatile Arylsulfonium Salts.

Producing sp3-hybridized carbon-enriched molecules is of particular interest due to their high success rate in clinical trials. The installation of aliphatic chains onto aromatic scaffolds was accomplished by nickel-catalyzed C(sp2)-C(sp3) cross-electrophile coupling with arylsulfonium salts. Thus, simple non-prefunctionalized arenes could be alkylated through the formation of aryldibenzothiophenium salts. The reaction employs an electrochemical approach to avoid potentially hazardous chemical redox agents, and importantly, the one-pot alkylation proved also viable, highlighting the robustness of our approach.

Palmitoyl transferase ZDHHC20 promotes pancreatic cancer metastasis.

Metastasis is one of the defining features of pancreatic ductal adenocarcinoma (PDAC) that contributes to poor prognosis. In this study, the palmitoyl transferase ZDHHC20 was identified in an in vivo short hairpin RNA (shRNA) screen as critical for metastatic outgrowth, with no effect on proliferation and migration in vitro or primary PDAC growth in mice. This phenotype is abrogated in immunocompromised animals and animals with depleted natural killer (NK) cells, indicating that ZDHHC20 affects the interaction of tumor cells and the innate immune system. Using a chemical genetics platform for ZDHHC20-specific substrate profiling, a number of substrates of this enzyme were identified. These results describe a role for palmitoylation in enabling distant metastasis that could not have been detected using in vitro screening approaches and identify potential effectors through which ZDHHC20 promotes metastasis of PDAC.

From Pixels to Prognosis: Unlocking the Potential of Deep Learning in Fibrotic Lung Disease Imaging Analysis.

The licensing of antifibrotic therapy for fibrotic lung diseases, including idiopathic pulmonary fibrosis IPF has created an urgent need for reliable biomarkers to predict disease progression and treatment response. Some patients experience stable disease trajectories, while others deteriorate rapidly, making treatment decisions challenging. High-resolution chest CT has become crucial for diagnosis, but visual assessments by radiologists suffer from low reproducibility and high interobserver variability. To address these issues, computer-based image analysis, called quantitative CT, has emerged. However, many quantitative CT methods rely on human input for training, therefore potentially incorporating human error into computer training. Rapid advances in artificial intelligence, specifically deep learning, aim to overcome this limitation by enabling autonomous quantitative analysis. While promising, deep learning also presents challenges including the need to minimize algorithm biases, ensuring explainability, and addressing accessibility and ethical concerns. This review explores the development and application of deep learning in improving the imaging process for fibrotic lung disease.

Influence of the substitution position on spin communication in photoexcited perylene-nitroxide dyads.

By virtue of the modularity of their structures, their tunable optical and magnetic properties, and versatile applications, photogenerated triplet-radical systems provide an ideal platform for the study of the factors controlling spin communication in molecular frameworks. Typically, these compounds consist of an organic chromophore covalently attached to a stable radical. After formation of the chromophore triplet state by photoexcitation, two spin centres are present in the molecule that will interact. The nature of their interaction is governed by the magnitude of the exchange interaction between them and can be studied by making use of transient electron paramagnetic resonance (EPR) techniques. Here, we investigate three perylene-nitroxide dyads that only differ with respect to the position where the nitroxide radical is attached to the perylene core. The comparison of the results from transient UV-vis and EPR experiments reveals major differences in the excited state properties of the three dyads, notably their triplet state formation yield, excited state deactivation kinetics, and spin coherence times. Spectral simulations and quantum chemical calculations are used to rationalise these findings and demonstrate the importance of considering the structural flexibility and the contribution of rotational conformers for an accurate interpretation of the data.

Intra-operative extracorporeal irradiation of tumour-invaded craniotomy bone flap in meningioma: a case series.

BACKGROUND: Extracorporeal irradiation of tumorous calvaria (EITC) can be performed to restore function and form of the skull after resection of bone-invasive meningioma. We sought to examine the rate of tumour recurrence and other selected outcomes in patients undergoing meningioma resection and EITC. METHODS: Retrospective single-centre study of adult patients undergoing meningioma resection and EITC between January 2015 and November 2022 at a tertiary neurosurgical centre. Patient demographics, surgery data, tumour data, use of adjuvant therapy, surgical complications, and tumour recurrences were collected. RESULTS: Eighteen patients with 11 (61%) CNS WHO grade 1, 6 (33%) grade 2, and 1 (6%) grade 3 meningiomas were included. Median follow-up was 42 months (range 3-88). Five (28%) patients had a recurrence, but none were associated with the bone flap. Two (11%) wound infections requiring explant surgery occurred. Six (33%) patients required a further operation. Two operations were for recurrences, one was for infection, one was a washout and wound exploration but no evidence of infection was found, one patient requested the removal of a small titanium implant, and one patient required a ventriculoperitoneal shunt for a persistent CSF collection. There were no cases of bone flap resorption and cosmetic outcome was not routinely recorded. CONCLUSION: EITC is feasible and fast to perform with good outcomes and cost-effectiveness compared to other reconstructive methods. We observed similar recurrence rates and lower infection rates requiring explant compared to the largest series of cranioplasty in meningioma. Cosmetic outcome is universally under-reported and should be reported in future studies.