Miracle-dz/UniFAR-FTUs huggingface dataset:
Multimodal data fusion of adult and pediatric brain tumors with deep learning

The introduction of deep learning in both imaging and genomics has significantly advanced the analysis of biomedical data. For complex diseases such as cancer different data modalities may reveal different disease characteristics, and the integration of imaging with genomic data has the potential to unravel additional information then when using these data sources in isolation. Here, we propose a DL framework that by combining histopathology images with gene expression profiles can predict prognosis of brain tumors. Using two separate cohorts of 783 adult and 305 pediatric brain tumors, the developed multimodal data models achieved better prediction results compared to the single data models, but also leads to the identification of more relevant biological pathways. Importantly, when testing our adult models on a third independent brain tumor dataset, we show our multimodal framework is able to generalize and performs better on new data from different cohorts. Furthermore, leveraging the concept of transfer learning, we demonstrate how our multimodal models pre-trained on pediatric glioma can be used to predict prognosis for two more rare (less available samples) pediatric brain tumors, i.e. ependymoma and medulloblastoma. To summarize, our study illustrates that a multimodal data fusion approach can be successfully implemented and customized to model clinical outcome of adult and pediatric brain tumors.
A Low-inclination Neutral Trans-Neptunian Object in an Extreme Orbit

We present photometric observations and numerical simulations of 2016 SD106, a low-inclination (i = 4.°8) extreme trans-Neptunian Object with a large semimajor axis (a = 350 au) and perihelion (q = 42.6 au). This object possesses a peculiar neutral color of g − r = 0.45 ± 0.05 and g − i = 0.72 ± 0.06, in comparison with other distant trans-Neptunian objects, all of which have moderate-red to ultra-red colors. A numerical integration based on orbital fitting on astrometric data covering eight years of arc confirms that 2016 SD106 is a metastable object without significant scattering evolution. Each of the clones survived at the end of the 1 Gyr simulation. However, very few neutral objects with inclinations <5° have been found in the outer solar system, even in the main Kuiper Belt. Furthermore, most mechanisms that lift perihelion distances are expected to produce a very low number of extreme objects with inclinations <5°. We thus explored the possibility that a hypothetical distant planet could increase the production of such objects. Our simulations show that no 2016 SD106–like orbits can be produced from three Kuiper Belt populations tested (i.e., plutinos, twotinos, and the Haumea Family) without the presence of a hypothetical planet, while a few similar orbits can be obtained with it; however, the presence of the additional planet produces a wide range of large semimajor-axis/large perihelion objects, in apparent contradiction with the observed scarcity of objects in those regions of phase space. Future studies may determine if there is a connection between the existence of a perihelion gap and a particular orbital configuration of a hypothetical distant planet.
Circulating Proteome for Pulmonary Nodule Malignancy

Background: While lung cancer low-dose computed tomography (LDCT) screening is being rolled out in many regions around the world, differentiation of indeterminate pulmonary nodules between malignant and benign remains to a challenge for screening programs. We conducted one of the first systematic investigations of circulating protein markers for their ability to assess the risk of malignancy for screen-detected pulmonary nodules. Methods: Based on four LDCT screening studies in the United States, Canada and Europe, we assayed 1078 unique protein markers in pre-diagnostic samples based on a nested case-control design with a total of 1253 participants. Protein markers were measured using proximity extension assays and the data were analyzed using multivariate logistic regression, random forest, and penalized regressions. Results: We identified 36 potentially informative markers differentiating malignant nodules from benign nodules. Pathway analysis revealed a tightly connected network based on the 36 protein-coding genes. We observed a differential mRNA expression profile of the corresponding 36 mRNAs between lung tumors and adjacent normal tissues using data from The Cancer Genomic Atlas. We prioritized a panel of 9 protein markers through 10-fold nested cross-validations. We observed that circulating protein markers can increase sensitivity to 0.80 for nodule malignancy compared to the Brock model (p-value<0.001). Two additional markers were identified that were specific for lung tumors diagnosed within one year. All 11 protein markers showed general consistency in improving prediction across the four LDCT studies. Conclusions: Circulating protein markers can help to differentiate between malignant and benign pulmonary nodules. Validating these results in an independent CT-screening study will be required prior to clinical implementation.
The additive effect of genetic modifiers on ALS prognosis: a population-based study

Objective. To determine if the co-presence of genetic polymorphisms related to ALS has additive effects on the course of the disease in a population-based cohort of Italian patients. Methods. The study population includes 1245 ALS patients identified through the Piemonte Register for ALS, diagnosed between 2007 and 2016 and not carrying SOD1, TARDBP and FUS mutations. Controls were 766 age, sex, and geographically matched Italian subjects. We considered UNC13A (rs12608932), CAMTA1 (rs2412208), SLC112A (rs407135) and ZNF512B (ZNF512B) polymorphisms, as well as ATXN2 polyQ intermediate repeats and C9ORF72 GGGGCC intronic expansion. Results. The variants in C9orf72 (p=0.016), ATXN2 (p<0.001) and UNC13A (p<0.001) were significantly related to survival in univariate analysis, while the other considered variants did not influence ALS outcome. However, in the Cox multivariable analysis, also CAMTA1 emerged to be independently related to survival. When assessing the interaction by pairs of genes, we found that the presence of both detrimental alleles/expansion was correlated with significantly shorter survival compared to subjects non-carrying both detrimental alleles/expansions. Each association of pairs of detrimental alleles was characterized by specific clinical phenotypes. Conclusions. We demonstrated that gene polymorphisms acting as genetic modifiers of ALS survival can act on their own or in unison. Overall, 54% of patients carried at least one detrimental common polymorphism or repeat expansion, highlighting the clinical impact of our findings. In addition, the identification of the synergic effects of modifier genes represents an essential clue for explaining ALS clinical heterogeneity and should be considered in designing and interpreting clinical trials.
E Pluribus Unum: Prospective acceptability benchmarking from the Contouring Collaborative for Consensus in Radiation Oncology (C3RO) Crowdsourced Initiative for Multi-Observer Segmentation

OBJECTIVE: Contouring Collaborative for Consensus in Radiation Oncology (C3RO) is a crowdsourced challenge engaging radiation oncologists across various expertise levels in segmentation. A challenge in artificial intelligence (AI) development is the paucity of multi-expert datasets; consequently, we sought to characterize whether aggregate segmentations generated from multiple non-experts could meet or exceed recognized expert agreement. MATERIALS AND METHODS: Participants who contoured [≥]1 region of interest (ROI) for the breast, sarcoma, head and neck (H&N), gynecologic (GYN), or gastrointestinal (GI) challenge were identified as a non-expert or recognized expert. Cohort-specific ROIs were combined into single simultaneous truth and performance level estimation (STAPLE) consensus segmentations. STAPLEnon-expert ROIs were evaluated against STAPLEexpert contours using Dice Similarity Coefficient (DSC). The expert interobserver DSC (IODSCexpert) was calculated as an acceptability threshold between STAPLEnon-expert and STAPLEexpert. To determine the number of non-experts required to match the IODSCexpert for each ROI, a single consensus contour was generated using variable numbers of non-experts and then compared to the IODSCexpert. RESULTS: For all cases, the DSC for STAPLEnon-expert versus STAPLEexpert were higher than comparator expert IODSCexpert for most ROIs. The minimum number of non-expert segmentations needed for a consensus ROI to achieve IODSCexpert acceptability criteria ranged between 2-4 for breast, 3-5 for sarcoma, 3-5 for H&N, 3-5 for GYN ROIs, and 3 for GI ROIs. DISCUSSION AND CONCLUSION: Multiple non-expert-generated consensus ROIs met or exceeded expert-derived acceptability thresholds. 5 non-experts could potentially generate consensus segmentations for most ROIs with performance approximating experts, suggesting non-expert segmentations as feasible cost-effective AI inputs.
New Medical Device and Therapeutic Approvals in Otolaryngology: State of the Art Review of 2021

Objective To evaluate new medical devices and drugs pertinent to otolaryngology–head and neck surgery that were approved by the Food and Drug Administration (FDA) in 2021. Data Sources Publicly available FDA device and drug approvals from ENT (ear, nose, and throat), anesthesia, neurosurgery, plastic surgery, and general surgery FDA committees. Review Methods FDA device and therapeutic approvals were identified and reviewed by members of the American Academy of Otolaryngology–Head and Neck Surgery’s Medical Devices and Drugs Committee. Two independent reviewers assessed the relevance of devices and drugs to otolaryngologists. Medical devices and drugs were then allocated to their respective subspecialty fields for critical review based on available scientific literature. Conclusions The Medical Devices and Drugs Committee reviewed 1153 devices and 52 novel drugs that received FDA approval in 2021 (67 ENT, 106 anesthesia, 618 general surgery and plastic surgery, 362 neurosurgery). Twenty-three devices and 1 therapeutic agent relevant to otolaryngology were included in the state of the art review. Advances spanned all subspecialties, including over-the-counter hearing aid options in otology, expanding treatment options for rhinitis in rhinology, innovative laser-safe endotracheal tubes in laryngology, novel facial rejuvenation and implant technology in facial plastic surgery, and advances in noninvasive and surgical treatment options for obstructive sleep apnea. Implications for Practice FDA approvals for new technology and pharmaceuticals present new opportunities across subspecialties in otolaryngology. Clinicians’ nuanced understanding of the safety, advantages, and limitations of these innovations ensures ongoing progress in patient care.
Exploring the role of the UK renal social worker: The nexus between health and social care for renal patients

Introduction Patients living with progressive chronic kidney disease may face a variety of ongoing physical, emotional, financial and/or social challenges along the disease pathway. In most UK renal units, psychosocial support has traditionally been provided by a renal social worker. However, in recent years, the numbers of renal social workers have been declining. The specialised role is poorly understood and there is no UK research about the profession. To inform future research and guide workforce planning, this study presents the first-ever exploration of the UK renal social worker role. It aimed to map the profession’s activities and reasons for involvement in patient care, as well as providing an initial evaluation of that involvement on patient wellbeing. Methods and analysis This mixed-method study recruited adult renal social workers (n = 14), who completed diaries over a 4-month period, participated in a focus group, and provided secondary data (caseload data and audit files where available) to give insight into their role. The evaluation of social work involvement on patient wellbeing used a pre-post intervention design. It measured distress, anxiety and depression levels as captured by the Distress Thermometer and Emotional Thermometers. A total of 161 patients completed the pre-involvement questionnaire, and 87 (55%) returned the post-involvement questionnaire. Results and conclusion The renal social worker role is creative, broad and fluid, with variations in roles linked to differences in employment and funding arrangements, configurations of the wider multidisciplinary renal team, level of standardisation of psychosocial care, availability of community services, and staff-to-patient ratios. Renal social work is different from statutory social work, and renal social workers are generally able to offer continuous rather than episodic care and support patients that would not meet strict local authority eligibility criteria. The findings showed that this support leads to significantly reduced distress and anxiety.
The use of telehealth in the provision of after-hours palliative care services in rural and remote Australia: A scoping review

Background Accessing quality palliative care, especially at the end of life is vital in reducing physical and emotional distress and optimising quality of life. For people living in rural and remote Australia, telehealth services can be effective in providing access to after-hours palliative care. Objective To review and map the available evidence on the use of telehealth in providing after-hours palliative care services in rural and remote Australia. Method Scoping review using Arksey and O’Malley methodological framework. Findings are reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Scopus, Web of Science, CINAHL Complete, Embase via Ovid, Emcare via Ovid, and Medline via Ovid databases were searched. Peer-reviewed studies and grey literature published in English from 2000 to May 2021 were included. Results Twelve studies were included in the review. Four main themes were identified: 1) Stakeholder perceptions of service; 2) benefits to services and users; 3) service challenges; and 4) recommendations for service improvement. Conclusion Telehealth can connect patients and families with healthcare professionals and enable patients to continue receiving care at home. However, challenges relating to patients, service, staff skills, and experience need to be overcome to ensure the success and sustainability of this service. Improved communication and care coordination, better access to patient records, and ongoing healthcare professional education are required. Implications Protocols, comprehensive policy documents and standardized operating procedures to guide healthcare professionals to provide after-hours palliative care is needed. Ongoing education and training for staff is crucial in managing patients’ symptoms. Existing service gaps need to be explored and alternative models of after-hours palliative care need to be tested.
Latent classes of men’s intimate partner violence perpetration and attitudes towards gender norms: A UN multi-country, cross-sectional study in Asia and the Pacific

Objective To examine distinct patterns of IPV perpetration and examined gender equitable attitudes as a correlate of these patterns among men from six countries in Asia and the Pacific. Design 2011–12 UN Multi-country Study on Men and Violence cross-sectional study. Setting Households in Bangladesh, Cambodia, China, Indonesia, Sri Lanka and Papua New Guinea. Participants 10,178 men aged 18–49 years residing in Bangladesh, Cambodia, China, Indonesia, Sri Lanka and Papua New Guinea. Primary outcomes measure Our primary outcome was distinct patterns of IPV perpetration which were derived from multilevel latent class analyses. Results The odds of being assigned to the Low All Forms of IPV Perpetration class than the High All Forms of IPV Perpetration class was lower for men in the middle tertile group than men in the high tertile group for gender equitable attitudes. The odds of being assigned to the High Emotional IPV Perpetration class than the High All Forms of IPV Perpetration class was greater for men in the low tertile group than men in the high tertile group for gender equitable attitudes. The odds of being assigned to the High Physical/Emotional/Economic IPV Perpetration class than the High All Forms of IPV Perpetration class was lower for men in the low tertile group than men in the high tertile group for gender equitable attitudes. Conclusions Gender transformative interventions that use an adaptive, personalized approach to men’s typology of IPV perpetration may be beneficial to reduce violence against for women in the Asia-Pacific region.
Efficacy and safety of high-dose esomeprazole–amoxicillin dual therapy for Helicobacter pylori rescue treatment: a multicenter, prospective, randomized, controlled trial

Abstract Background: High-dose dual therapy (HDDT) with proton pump inhibitors (PPIs) and amoxicillin has attracted widespread attention due to its favorable efficacy in eradicating Helicobacter pylori (H. pylori). This study aimed to compare the efficacy and safety of high-dose PPI–amoxicillin dual therapy and bismuth-containing quadruple therapy for H. pylori rescue treatment. Methods: This was a prospective, randomized, multicenter, non-inferiority trial. Patients recruited from eight centers who had failed previous treatment were randomly (1:1) allocated to two eradication groups: HDDT (esomeprazole 40 mg and amoxicillin 1000 mg three times daily; the HDDT group) and bismuth-containing quadruple therapy (esomeprazole 40 mg, bismuth potassium citrate 220 mg, and furazolidone 100 mg twice daily, combined with tetracycline 500 mg three times daily; the tetracycline, furazolidone, esomeprazole, and bismuth [TFEB] group) for 14 days. The primary endpoint was the H. pylori eradication rate. The secondary endpoints were adverse effects, symptom improvement rates, and patient compliance. Results: A total of 658 patients who met the criteria were enrolled in this study. The HDDT group achieved eradication rates of 75.4% (248/329), 81.0% (248/306), and 81.3% (248/305) asdetermined by the intention-to-treat (ITT), modified intention-to-treat (MITT), and per-protocol (PP) analyses, respectively. The eradication rates were similar to those in the TFEB group: 78.1% (257/329), 84.2% (257/305), and 85.1% (257/302). The lower 95% confidence interval boundary (−9.19% in the ITT analysis, − 9.21% in the MITT analysis, and −9.73% in the PP analysis) was greater than the predefined non-inferiority margin of −10%, establishing a non-inferiority of the HDDT group vs. the TFEB group. The incidence of adverse events in the HDDT group was significantly lower than that in the TFEB group (11.1% vs. 26.8%, P < 0.001). Symptom improvement rates and patients’ compliance were similar between the two groups. Conclusions: Fourteen-day HDDT is non-inferior to bismuth-containing quadruple therapy, with fewer adverse effects and good treatment compliance, suggesting HDDT as an alternative for H. pylori rescue treatment in the local region. Trial registration: Clinicaltrials.gov, NCT04678492.
Extrinsic and intrinsic drivers of parasite prevalence and parasite species richness in a marine bivalve

Parasite species richness is influenced by a range of drivers including host related factors (e.g. host size) and environmental factors (e.g. seawater temperature). However, identification of modulators of parasite species richness remains one of the great unanswered questions in ecology. The common cockle Cerastoderma edule is renowned for its diversity and abundance of parasites, yet drivers of parasite species richness in cockles have not been examined to investigate the association of both macro and microparasite communities. Using cockles as a model species, some of the key drivers of parasite prevalence and parasite species richness were investigated. Objectives of this 19-month survey were to determine the influence of the environment, host-parasite dynamics and parasite associations on parasite species richness and prevalence at two different geographic latitudes, chosen based on environmental differences. The highest parasite species richness was recorded in the northern sites, and this was potentially influenced by a range of interactions between the host, the pathogens and the environment. Parasite prevalence increased with host size and age, and parasite species richness increased with reduced salinity. A number of interactions between parasites, and between parasites and pathologies may be influencing parasite infection dynamics. New and concerning information is also presented regarding interactions between parasites and their environment. A number of parasites and potential pathogens (bacteria, Trichodina ciliates, metacercariae, trematode sporocysts) may be advantaged under climate change conditions (warming seas, increased precipitation), increasing disease incidence, which may prove detrimental not just for cockles, but for other bivalve species in the future.
Low rate of SARS-CoV-2 incident infection identified by weekly screening PCR in a prospective year-long cohort study

Background Asymptomatic and pre-symptomatic SARS-CoV-2 infections may contribute to ongoing community transmission, however, the benefit of routine screening of asymptomatic individuals in low-risk populations is unclear. Methods To identify SARS-CoV-2 infections 553 seronegative individuals were prospectively followed for 52 weeks. From 4/2020-7/2021, participants submitted weekly self-collected nasal swabs for rtPCR and completed symptom and exposure surveys. Results Incident SARS2-CoV-2 infections were identified in 9/553 (1.6%) participants. Comparisons of SARS2-CoV-2(+) to SARS2-CoV-2(-) participants revealed significantly more close contacts outside the household (median: 5 versus 3; p = 0.005). The incidence of infection was higher among unvaccinated/partially vaccinated than among fully vaccinated participants (9/7,679 versus 0/6,845 person-weeks; p = 0.004). At notification of positive test result, eight cases were symptomatic and one pre-symptomatic. Conclusions These data suggest that weekly SARS2-CoV2 surveillance by rtPCR did not efficiently detect pre-symptomatic infections in unvaccinated participants.
Surface reflectance of Mars observed by CRISM/MRO: 2. Estimation of surface photometric properties in Gusev Crater and Meridiani Planum

The present article proposes an approach to analyze the photometric properties of the surface materials from multi‐angle observations acquired by the Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) on‐board the Mars Reconnaissance Orbiter. We estimate photometric parameters using Hapke's model in a Bayesian inversion framework. This work also represents a validation of the atmospheric correction provided by the Multi‐angle Approach for Retrieval of Surface Reflectance from CRISM Observations (MARS‐ReCO) proposed in the companion article. The latter algorithm retrieves photometric curves of surface materials in reflectance units after removing the aerosol contribution. This validation is done by comparing the estimated photometric parameters to those obtained from in situ measurements by Panoramic Camera instrument at the Mars Exploration Rover (MER) Spirit and MER Opportunity landing sites. Consistent photometric parameters with those from in situ measurements are found, demonstrating that MARS‐ReCO gives access to accurate surface reflectance. Moreover, the assumption of a non‐Lambertian surface as included in MARS‐ReCO is shown to be significantly more precise to estimate surface photometric properties from space in comparison to methods based on a Lambertian surface assumption. In the future, the presented method will allow us to map from orbit the surface bidirectional reflectance and the related photometric parameters in order to characterize the Martian surface.