Miracle-dz/UniFAR-FTUs huggingface dataset:
A Transformer-Based Model for Zero-Shot Health Trajectory Prediction

Integrating modern machine learning and clinical decision-making has great promise for mitigating healthcares increasing cost and complexity. We introduce the Enhanced Transformer for Health Outcome Simulation (ETHOS), a novel application of the transformer deep-learning architecture for analyzing high-dimensional, heterogeneous, and episodic health data. ETHOS is trained using Patient Health Timelines (PHTs)-detailed, tokenized records of health events-to predict future health trajectories, leveraging a zero-shot learning approach. ETHOS represents a significant advancement in foundation model development for healthcare analytics, eliminating the need for labeled data and model fine-tuning. Its ability to simulate various treatment pathways and consider patient-specific factors positions ETHOS as a tool for care optimization and addressing biases in healthcare delivery. Future developments will expand ETHOS capabilities to incorporate a wider range of data types and data sources. Our work demonstrates a pathway toward accelerated AI development and deployment in healthcare.
Intrahost evolution leading to distinct lineages in the upper and lower respiratory tracts during SARS-CoV-2 prolonged infection

Accumulating evidence points to persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in immunocompromised individuals as a source of genetically divergent, novel lineages, generally characterised by increased transmissibility and immune escape. While intrahost evolutionary dynamics of the virus in chronically infected patients have been previously reported, existing knowledge is primarily based on samples obtained from the nasopharyngeal compartment. In this study, we investigate the intrahost evolution and genetic diversity that accumulated during a prolonged SARS-CoV-2 infection with the Omicron sublineage BF.7, estimated to have persisted for over one year in an immunosuppressed patient. Based on the sequencing of eight viral genomes collected from the patient at six time points, we identified 86 intrahost single-nucleotide variants (iSNVs), two indels, and a 362 bp deletion. Our analysis revealed distinct viral genotypes in the nasopharyngeal (NP), endotracheal aspirate (ETA), and bronchoalveolar (BAL) samples. Notably, while significant divergence was observed between NP and BAL samples, most of the iSNVs found in ETA samples were also detected in NP or BAL samples. This suggests that NP samples may not offer a comprehensive representation of the overall intrahost viral diversity. Nonsynonymous mutations were most frequent in the spike and envelope genes, along with loss-of-function mutations in ORF8, generated by a frameshift mutation and a large deletion detected in the BAL and NP samples, respectively. Using long-range PCR on SARS-CoV-2 samples sequenced as part of routine surveillance, we validated that similar deletions causing ORF8 loss of function can be carried by SARS-CoV-2 during acute infection. Our findings not only demonstrate that the Omicron sublineage BF.7 can further diverge from its already exceptionally mutated state but also highlight that patients chronically infected with SARS-CoV-2 can develop genetically specific viral populations across distinct anatomical compartments. This provides novel insights into the intricate nature of viral diversity and evolution dynamics in persistent infections.
The Adhesive Capsulitis Corticosteroid and Dilation (ACCorD) randomized controlled trial

Aims Is it feasible to conduct a definitive multicentre trial in community settings of corticosteroid injections (CSI) and hydrodilation (HD) compared to CSI for patients with frozen shoulder? An adequately powered definitive randomized controlled trial (RCT) delivered in primary care will inform clinicians and the public whether hydrodilation is a clinically and cost-effective intervention. In this study, prior to a full RCT, we propose a feasibility trial to evaluate recruitment and retention by patient and clinician willingness of randomization; rates of withdrawal, crossover and attrition; and feasibility of outcome data collection from routine primary and secondary care data. Methods In the UK, the National Institute for Health and Care Excellence (NICE) advises that prompt early management of frozen shoulder is initiated in primary care settings with analgesia, physiotherapy, and joint injections; most people can be managed without an operation. Currently, there is variation in the type of joint injection: 1) CSI, thought to reduce the inflammation of the capsule reducing pain; and 2) HD, where a small volume of fluid is injected into the shoulder joint along with the steroid, aiming to stretch the capsule of the shoulder to improve pain, but also allowing greater movement. The creation of musculoskeletal hubs nationwide provides infrastructure for the early and effective management of frozen shoulder. This potentially reduces costs to individuals and the wider NHS perhaps negating the need for a secondary care referral. Results We will conduct a multicentre RCT comparing CSI and HD in combination with CSI alone. Patients aged 18 years and over with a clinical diagnosis of frozen shoulder will be randomized and blinded to receive either CSI and HD in combination, or CSI alone. Feasibility outcomes include the rate of randomization as a proportion of eligible patients and the ability to use routinely collected data for outcome evaluation. This study has involved patients and the public in the trial design, dissemination methods, and how to include groups who are underserved by research. Conclusion We will disseminate findings among musculoskeletal clinicians via the British Orthopaedic Association, the Chartered Society of Physiotherapy, the Royal College of Radiologists, and the Royal College of General Practitioners. To ensure wide reach we will communicate findings through our established network of charities and organizations, in addition to preparing dissemination findings in Bangla and Urdu (commonly spoken languages in northeast London). If a full trial is shown to be feasible, we will seek additional National Institute for Health and Care Research funding for a definitive RCT. This definitive study will inform NICE guidelines for the management of frozen shoulder. Cite this article: Bone Jt Open 2024;5(3):162–173.
Protocol: Strategy instruction for improving short‐ and long‐term writing performance on secondary and upper‐secondary students: A systematic review

Abstract This is the protocol for a Campbell systematic review. The objectives are as follows. This review aims to investigate the effectiveness of all types of teacher‐delivered classroom‐based strategy instruction aimed at students in the general population (all students) including struggling students (with or at‐risk of academic difficulties) in ages 12–19 for increasing writing performance. The majority of previous reviews scoped all outcomes presented in the primary studies. This review will solely focus on covering three most common outcomes: story quality, story elements and word count/length.
On epigenetic stochasticity, entropy and cancer risk

Epigenetic changes are known to accrue in normal cells as a result of ageing and cumulative exposure to cancer risk factors. Increasing evidence points towards age-related epigenetic changes being acquired in a quasi-stochastic manner, and that they may play a causal role in cancer development. Here, I describe the quasi-stochastic nature of DNA methylation (DNAm) changes in ageing cells as well as in normal cells at risk of neoplastic transformation, discussing the implications of this stochasticity for developing cancer risk prediction strategies, and in particular, how it may require a conceptual paradigm shift in how we select cancer risk markers. I also describe the mounting evidence that a significant proportion of DNAm changes in ageing and cancer development are related to cell proliferation, reflecting tissue-turnover and the opportunity this offers for predicting cancer risk via the development of epigenetic mitotic-like clocks. Finally, I describe how age-associated DNAm changes may be causally implicated in cancer development via an irreversible suppression of tissue-specific transcription factors that increases epigenetic and transcriptomic entropy, promoting a more plastic yet aberrant cancer stem-cell state. This article is part of a discussion meeting issue ‘Causes and consequences of stochastic processes in development and disease’.
P Wave Anisotropic Tomography of the SE Tibetan Plateau: Evidence for the Crustal and Upper‐Mantle Deformations

The upper crust in the SE Tibetan Plateau is rotating around the eastern Himalayan syntax clockwise, and the western margin of the Yangtze Craton has been involved in the active tectonics. However, it is still unclear whether and how the deep crust and upper mantle respond to the plateau expansion. In this study we present a high‐resolution three‐dimensional model of P wave velocity tomography and azimuthal anisotropy in the crust and uppermost mantle beneath the SE Tibetan Plateau determined using traveltime data recorded by a dense seismic network. Widespread low‐velocity zones are revealed around a high‐velocity body in the deep crust and uppermost mantle beneath the southwest Yangtze Craton, where fast‐velocity directions of the azimuthal anisotropy are mostly parallel to the contour lines of the surface topography and the Moho depth along the plateau margin. These results indicate that gravitational potential plays an important role in the crustal and uppermost‐mantle deformations in the SE Tibetan Plateau. Meanwhile, the shallow crust may drop down to the deep crust and drive the ductile deep‐crustal material to intrude into the adjacent regions. The extruded crust is trapped in a deep‐crustal corner and obstructed by the surrounding strong blocks. The trapped crustal material may rise up, causing significant uplift and high heat flow at the surface.
A climatology of quasi‐linear convective systems and associated synoptic‐scale environments in southern Brazil

This study presents a 9‐year climatology and composite analysis of quasi‐linear convective systems (QLCSs) in southern Brazil (SB). QLCSs are identified using radar imagery and defined as a 100‐km long, 40‐dBZ convective line that lasts for at least 1 hr. QLCS cases associated with at least three severe wind reports are classified as severe. Composites of the synoptic‐scale environments and severe convective weather parameters are constructed for severe and non‐severe cases of three synoptic patterns found as the most recurrent in QLCS cases. QLCSs are more frequent and more likely to be severe during spring, while very few cases occur during winter. Most cases occur during late night and morning, corroborating previous research of mesoscale convective systems in this area, but the percentages of severe cases are higher in late afternoon and early night. Faster QLCSs, particularly those with velocities greater than 50 km/hr, have higher probability of being severe in comparison to slower systems. The three synoptic patterns more often related to QLCS occurrence in SB are characterized by a mid‐level trough upstream of SB (type 1), a mid‐level trough west of the Andes (type 2) and predominance of zonal flow over SB (type 3). In general, there is a low‐pressure system over northwestern Argentina extending a trough to SB, where low‐level moisture flux convergence and warm advection occur. In severe cases, the sea‐level pressure is lower in northwestern Argentina and there is greater low‐level northwesterly flow over SB. The type 1 is the most frequent pattern when QLCSs are observed in SB and is also the type with higher percentage of severe cases. Convective available potential energy (CAPE) and downdraft CAPE are good discriminators between severe and non‐severe cases in type 1 and 2 environments, while the 1,000–500‐hPa bulk wind difference is a better predictor in type 3 cases.
Trajectory of adjustment difficulties following disaster: 10-year longitudinal cohort study

Background Although much is known about psychopathology such as post-traumatic stress disorder (PTSD) and depression following bushfire (also known as wildfire), little is known about prevalence, trajectory and impacts for those experiencing general adjustment difficulties following exposure to these now-common events. Aims This was an exploratory analysis of a large cohort study that examined the prevalence, trajectory and risk factors of probable adjustment disorder over a 10-year period following bushfire exposure. Method The Beyond Bushfires study assessed individuals exposed to a large and deadly bushfire across three time points spanning 10 years. Self-report survey data from participants from areas with moderate and high levels of fire-affectedness were analysed: n = 802 participants at Wave 1 (3–4 years post-fires), n = 596 at Wave 2 (5 years post-fires) and n = 436 at Wave 3 (10 years post-fires). Surveys indexed fire-related experiences and post-fire stressors, and comprised the six-item Kessler Psychological Distress Scale (probable adjustment disorder index), four-item Posttraumatic Stress Disorder Checklist (probable fire-related PTSD) and nine-item Patient Health Questionnaire (probable major depressive episode). Results Prevalence of probable adjustment disorder was 16% (Wave 1), 15% (Wave 2) and 19% (Wave 3). Probable adjustment disorder at 3–4 years post-fires predicted a five-fold increase in risk for escalating to severe psychiatric disorder (i.e. probable fire-related PTSD/major depressive episode) at 10 years post-fires, and was associated with post-fire income and relationship stressors. Conclusions Adjustment difficulties are prevalent post-disaster, many of which are maintained and exacerbated over time, resulting in increased risk for later disorder and adaptation difficulties. Psychosocial interventions supporting survivors with adjustment difficulties may prevent progression to more severe disorder.
Finite Element Analysis of Suction Bucket Foundations in Sand Subjected to Cyclic Loading

A suction bucket or suction caisson is a foundation concept for supporting offshore installations. The practical experience related to this concept is mainly based on applications in the oil and gas industry. Observations show significant difference in response for wind turbines compared to more traditional installations offshore. The lightweight structure of a wind turbine makes the caisson susceptible to cyclic loading due to metocean conditions. As this foundation concept is being increasingly considered for offshore wind turbines, a proper understanding of its behaviour is important for a functional and effective design of suction caissons for this purpose. A series of centrifuge experiments have been performed at the University of Western Australia to investigate the response of a suction caisson in dense Baskarp sand. The experiments aim to represent the load conditions of a caisson supporting an offshore wind turbine in the North Sea. Raw data from the centrifuge experiments have in this thesis been analysed focusing on the cyclic response, and the work demonstrates a significant difference in response for compression and tension loading. The permeability of the soil is also found to be decisive for the caisson response. A model of the centrifuge experiment in prototype scale is in this study recreated in the finite element software PLAXIS. Model parameters are based on tests on similar sand available at NGI, due to limitations of sand specific cyclic laboratory tests related to the centrifuge experiments. Arbitrary sets of parameters, representing sands of different densities, are also considered. Loads identical to those of the centrifuge experiments is applied to the simulations. Results from the simulations differ from the centrifuge experiments. Displacements are in general underestimated and total stress and pore pressure are overestimated. Several reasons to the differences are discussed in the thesis, and these are assumed to be related to calibration of the permeability, loosening of the sand due to installation, lack of fully contact between caisson lid and soil in addition to air bubbles in the pore fluid. The differences emphasise the challenge of capturing all features of the complex caisson response in a simplified model.
The Progress and Prospects of Immune Cell Therapy for the Treatment of Cancer

Immune cell therapy as a revolutionary treatment modality, significantly transformed cancer care. It is a specialized form of immunotherapy that utilizes living immune cells as therapeutic reagents for the treatment of cancer. Unlike traditional drugs, cell therapies are considered “living drugs,” and these products are currently customized and require advanced manufacturing techniques. Although chimeric antigen receptor (CAR)-T cell therapies have received tremendous attention in the industry regarding the treatment of hematologic malignancies, their effectiveness in treating solid tumors is often restricted, leading to the emergence of alternative immune cell therapies. Tumor-infiltrating lymphocytes (TIL) cell therapy, cytokine-induced killer (CIK) cell therapy, dendritic cell (DC) vaccines, and DC/CIK cell therapy are designed to use the body’s natural defense mechanisms to target and eliminate cancer cells, and usually have fewer side effects or risks. On the other hand, cell therapies, such as chimeric antigen receptor-T (CAR-T) cell, T cell receptor (TCR)-T, chimeric antigen receptor-natural killer (CAR-NK), or CAR-macrophages (CAR-M) typically utilize either autologous stem cells, allogeneic or xenogeneic cells, or genetically modified cells, which require higher levels of manipulation and are considered high risk. These high-risk cell therapies typically hold special characteristics in tumor targeting and signal transduction, triggering new anti-tumor immune responses. Recently, significant advances have been achieved in both basic and clinical researches on anti-tumor mechanisms, cell therapy product designs, and technological innovations. With swift technological integration and a high innovation landscape, key future development directions have emerged. To meet the demands of cell therapy technological advancements in treating cancer, we comprehensively and systematically investigate the technological innovation and clinical progress of immune cell therapies in this study. Based on the therapeutic mechanisms and methodological features of immune cell therapies, we analyzed the main technical advantages and clinical transformation risks associated with these therapies. We also analyzed and forecasted the application prospects, providing references for relevant enterprises with the necessary information to make informed decisions regarding their R&D direction selection.
The neuroanatomy of visual extinction following right hemisphere brain damage: Insights from multivariate and Bayesian lesion analyses in acute stroke

Abstract Multi‐target attention, that is, the ability to attend and respond to multiple visual targets presented simultaneously on the horizontal meridian across both visual fields, is essential for everyday real‐world behaviour. Given the close link between the neuropsychological deficit of extinction and attentional limits in healthy subjects, investigating the anatomy that underlies extinction is uniquely capable of providing important insights concerning the anatomy critical for normal multi‐target attention. Previous studies into the brain areas critical for multi‐target attention and its failure in extinction patients have, however, produced heterogeneous results. In the current study, we used multivariate and Bayesian lesion analysis approaches to investigate the anatomical substrate of visual extinction in a large sample of 108 acute right hemisphere stroke patients. The use of acute stroke patient data and multivariate/Bayesian lesion analysis approaches allowed us to address limitations associated with previous studies and so obtain a more complete picture of the functional network associated with visual extinction. Our results demonstrate that the right temporo‐parietal junction (TPJ) is critically associated with visual extinction. The Bayesian lesion analysis additionally implicated the right intraparietal sulcus (IPS), in line with the results of studies in neurologically healthy participants that highlighted the IPS as the area critical for multi‐target attention. Our findings resolve the seemingly conflicting previous findings, and emphasise the urgent need for further research to clarify the precise cognitive role of the right TPJ in multi‐target attention and its failure in extinction patients.
Exploring the meaning of a good life for older widows with extensive need of care: a qualitative in-home interview study

ABSTRACT Introduction Studies of older women’s life transitions is rare but gains relevance as the aging population, with older women as the majority, expands. Purpose To explore the meaning of a good life for older widows with extensive home care needs. Materials and methods Semi-structured interviews were carried out with eleven women, aged 80 and over (82–95 years, mean 90) residing at home with extensive care needs (≥4 daily sessions, averaging 2.5–6 hours, mean 3). Data were analysed by reflexive thematic analysis. Results The theme “This Day in My Home, the frame of my life” reflects the women’s experience of a good life. A good day imbued them with hope, trust and security, carrying them forward with the assurance that night would usher in a new day. However, there were moments when life was merely about navigating daily challenges. During such days, the women felt trapped in time, unsafe and lonely. Conclusion A day at home may seem static, yet it mirrors life’s dynamism, evolving with shifting circumstances. Older widows navigate challenges while maintaining their sense of self, independence, and connection to home. These findings have implications for aged care, recognizing the multifaceted aspects of life and the centrality of home.