Miracle-dz/UniFAR-FTUs huggingface dataset:
LiSNet: An AI-based tool for liver imaging staging of hepatocellular carcinoma aggressiveness.

BACKGROUND Presurgical assessment of hepatocellular carcinoma (HCC) aggressiveness can benefit patients' treatment options and prognosis. PURPOSE To develop an artificial intelligence (AI) tool, namely, LiSNet, in the task of scoring and interpreting HCC aggressiveness with computed tomography (CT) imaging. METHODS A total of 358 patients with HCC undergoing curative liver resection were retrospectively included. Three subspecialists were recruited to pixel-wise annotate and grade tumor aggressiveness based on CT imaging. LiSNet was trained and validated in 193 and 61 patients with a deep neural network to emulate the diagnostic acumen of subspecialists for staging HCC. The test set comprised 104 independent patients. We subsequently compared LiSNet with an experience-based binary diagnosis scheme and human-AI partnership that combined binary diagnosis and LiSNet for assessing tumor aggressiveness. We also assessed the efficiency of LiSNet for predicting survival outcomes. RESULTS At the pixel-wise level, the agreement rate of LiSNet with subspecialists was 0.658 (95% confidence interval [CI]: 0.490-0.779), 0.595 (95% CI: 0.406-0.734), and 0.369 (95% CI: 0.134-0.566), for scoring HCC aggressiveness grade I, II, and III, respectively. Additionally, LiSNet was comparable to subspecialists for predicting histopathological microvascular invasion (area under the curve: LiSNet: 0.668 [95% CI: 0.559-0.776] vs. subspecialists: 0.699 [95% CI: 0.591-0.806], p > 0.05). In a human-AI partnered diagnosis, combining LiSNet and experience-based binary diagnosis can achieve the best predictive ability for microvascular invasion (area under the curve: 0.705 [95% CI: 0.589-0.820]). Furthermore, LiSNet was able to indicate overall survival after surgery. CONCLUSION The designed LiSNet tool warrants evaluation as an alternative tool for radiologists to conduct automatic staging of HCC aggressiveness at the pixel-wise level with CT imaging. Its prognostic value might benefit patients' treatment options and survival prediction. This article is protected by copyright. All rights reserved.
Exposures to pesticides and risk of cancer: Evaluation of recent epidemiological evidence in humans and paths forward

Knowledge of the role in cancer etiology of environmental exposures as pesticides is a prerequisite for primary prevention. We review 63 epidemiological studies on exposure to pesticides and cancer risk in humans published from 2017 to 2021, with emphasis on new findings, methodological approaches, and gaps in the existing literature. While much of the recent evidence suggests causal relationships between pesticide exposure and cancer, the strongest evidence exists for acute myeloid leukemia (AML) and colorectal cancer (CRC), diseases in which the observed associations were consistent across several studies, including high‐quality prospective studies and those using biomarkers for exposure assessment, with some observing dose‐response relationships. Though high‐quality studies have been published since the IARC monograph on organophosphate insecticides in 2017, there are still gaps in the literature on carcinogenic evidence in humans for a large number of pesticides. To further knowledge, we suggest leveraging new techniques and methods to increase sensitivity and precision of exposure assessment, incorporate multi‐omics data, and investigate more thoroughly exposure to chemical mixtures. There is also a strong need for better and larger population‐based cohort studies that include younger and nonoccupationally exposed individuals, particularly during developmental periods of susceptibility. Though the existing evidence has limitations, as always in science, there is sufficient evidence to implement policies and regulatory action that limit pesticide exposure in humans and, hence, further prevent a significant burden of cancers.
Continuous subcutaneous insulin infusion is associated with a better glycemic control than multiple daily insulin injections without difference in diabetic ketoacidosis and hypoglycemia admissions among Emiratis with Type 1 diabetes

Aims To characterizes Emiratis patients with Type 1 diabetes (T1D) and compares outcomes between continuous subcutaneous insulin infusion (CSII) versus multiple daily insulin injections (MDI) users. The WHO-Five Well-Being Index (WHO-5) score was used to screen for depression. Methods In this cross-sectional study; sociodemographic, clinical characteristics and insulin replacement regimens were collected on patients with T1D between 2015–2018. Results 134 patients with mean age of 20.9±7.5 years were included. Females constitute 56.7% and 50.7% had diabetes duration of >10 years. Diabetic ketoacidosis (DKA) at presentation was reported in 46.3%. Average glycemic control over preceding 12months was satisfactory (less than 7.5%), suboptimal (7.5–9%), and poor (more than 9%) in 26.6%, 42.7% & 30.6% of the patients, respectively. Higher proportion of patients using CSII achieved satisfactory or suboptimal glycemic control compared to patients with MDI (P = 0.003). The latest median /IQR HbA1c was significantly lower (P = 0.041) in patients using CSII (8.2 /1.93%) compared to MDI (8.5/2.45%). There was no significant difference between two groups in DKA, severe hypoglycemia or total WHO-5 score. Conclusions CSII usage was associated with better glycemic control than MDI, although no difference in DKA and severe hypoglycemia. The overall glycemic control among Emiratis subjects with T1D is unsatisfactory and needs more rigorous patient counseling and education.
Obesity Classification of the Body Mass Index Does Not Predict Participation Restrictions at Work

The BMI classification of obesity is a widely used system. However, when it comes to occupational participation restrictions, the BMI-classification is of little value. Modern work environments do not pose high physical demands, allowing people of every BMI group to fulfil common job requirements. Objective The objective was to explore the differences of the three body mass index (BMI) obesity classes regarding sociodemographic data, medical and psychological well-being, but especially participation restrictions at work. Methods A specialist in psychosomatic medicine reported on the health and occupational status of 190 patients (BMI >30), who were treated as inpatients in a psychosomatic rehabilitation unit. Results Significant increases in severity or work limitations were found for higher BMI groups concerning metabolic, cardiologic, and orthopedic comorbidity. There were no differences regarding indicators of occupational participation. Independent of the obesity status, about three quarters were seen as fit for work. Conclusions The initial hypothesis is rejected, as no difference concerning objective parameters of work participation were found between the BMI classes. The data suggest that BMI class I to BMI class III do not allow predictions of the ability to work.
Insights into established and emerging roles of SR protein family in plants and animals

Splicing of pre‐mRNA is an essential part of eukaryotic gene expression. Serine‐/arginine‐rich (SR) proteins are highly conserved RNA‐binding proteins present in all metazoans and plants. SR proteins are involved in constitutive and alternative splicing, thereby regulating the transcriptome and proteome diversity in the organism. In addition to their role in splicing, SR proteins are also involved in mRNA export, nonsense‐mediated mRNA decay, mRNA stability, and translation. Due to their pivotal roles in mRNA metabolism, SR proteins play essential roles in normal growth and development. Hence, any misregulation of this set of proteins causes developmental defects in both plants and animals. SR proteins from the animal kingdom are extensively studied for their canonical and noncanonical functions. Compared with the animal kingdom, plant genomes harbor more SR protein‐encoding genes and greater diversity of SR proteins, which are probably evolved for plant‐specific functions. Evidence from both plants and animals confirms the essential role of SR proteins as regulators of gene expression influencing cellular processes, developmental stages, and disease conditions.
A coarse‐grained approach to NMR‐data‐assisted modeling of protein structures

The ESCASA algorithm for analytical estimation of proton positions from coarse‐grained geometry developed in our recent work has been implemented in modeling protein structures with the highly coarse‐grained UNRES model of polypeptide chains (two sites per residue) and nuclear magnetic resonance (NMR) data. A penalty function with the shape of intersecting gorges was applied to treat ambiguous distance restraints, which automatically selects consistent restraints. Hamiltonian replica exchange molecular dynamics was used to carry out the conformational search. The method was tested with both unambiguous and ambiguous restraints producing good‐quality models with GDT_TS from 7.4 units higher to 14.4 units lower than those obtained with the CYANA or MELD software for protein‐structure determination from NMR data at the all‐atom resolution. The method can thus be applied in modeling the structures of flexible proteins, for which extensive conformational search enabled by coarse‐graining is more important than high modeling accuracy.
Connectivity among thermal habitats buffers the effects of warm climate on life‐history traits and population dynamics

Abstract Contemporary climate change affects population dynamics, but its influence varies with landscape structure. It is still unclear whether landscape fragmentation buffers or amplifies the effects of climate on population size and the age and body size of individuals composing these populations. This study aims to investigate the impacts of warm climates on lizard life‐history traits and population dynamics in habitats that vary in their connectivity. We monitored common lizard Zootoca vivipara populations for 3 years in an experimental system in which both climatic conditions and connectivity among habitats were simultaneously manipulated. We considered two climatic treatments (i.e. present‐day climate and warm climate [+1.4°C than present‐day climate]) and two connectivity treatments (i.e. a connected treatment in which individuals could move from one climate to the other and an isolated treatment in which movement between climates was not possible). We monitored survival, reproduction, growth, dispersal, age and body size of each individual in the system as well as population density through time. We found that the influence of warm climates on life‐history traits and population dynamics depended on connectivity among thermal habitats. Populations in warm climates were (i) composed of younger individuals only when isolated; (ii) larger in population size only in connected habitats and (iii) composed of larger age‐specific individuals independently of the landscape configuration. The connectivity among habitats altered population responses to climate warming likely through asymmetries in the flow and phenotype of dispersers between thermal habitats. Our results demonstrate that landscape fragmentation can drastically change the dynamics and persistence of populations facing climate change.
Efficacy of JAK 1/2 inhibition in murine immune bone marrow failure.

Immune aplastic anemia (AA) is a severe blood disease characterized by T-lymphocyte mediated stem cell destruction. Hematopoietic stem cell transplant and immunosuppression are effective but entail costs and risks and are not always successful. The Janus Kinase (JAK) 1/2 inhibitor ruxolitinib (RUX) suppresses cytotoxic T cell activation and inhibits cytokine production in models of graft-versus-host disease. We tested RUX in murine immune AA for potential therapeutic benefit. After infusion of lymph node (LN) cells mismatched at the major histocompatibility complex [C67BL/6 (B6)ÞCByB6F1], RUX, administered as a food additive (Rux-chow), attenuated bone marrow hypoplasia, ameliorated peripheral blood pancytopenia, preserved hematopoietic progenitors, and prevented mortality, when used either prophylactically or therapeutically. RUX suppressed the infiltration, proliferation, and activation of effector T cells in the bone marrow and mitigated Fas-mediated apoptotic destruction of target hematopoietic cells. Similar effects were obtained when Rux-chow was fed to C.B10 mice in a minor histocompatibility antigen mismatched (B6ÞC.B10) AA model. RUX only modestly suppressed lymphoid and erythroid hematopoiesis in normal and irradiated CByB6F1 mice. Our data supports clinical trials of JAK/STAT inhibitors in human AA and other immune bone marrow failure syndromes.
Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS.

BACKGROUND The intrathecally administered antisense oligonucleotide tofersen reduces synthesis of the superoxide dismutase 1 (SOD1) protein and is being studied in patients with amyotrophic lateral sclerosis (ALS) associated with mutations in SOD1 (SOD1 ALS). METHODS In this phase 3 trial, we randomly assigned adults with SOD1 ALS in a 2:1 ratio to receive eight doses of tofersen (100 mg) or placebo over a period of 24 weeks. The primary end point was the change from baseline to week 28 in the total score on the ALS Functional Rating Scale-Revised (ALSFRS-R; range, 0 to 48, with higher scores indicating better function) among participants predicted to have faster-progressing disease. Secondary end points included changes in the total concentration of SOD1 protein in cerebrospinal fluid (CSF), in the concentration of neurofilament light chains in plasma, in slow vital capacity, and in handheld dynamometry in 16 muscles. A combined analysis of the randomized component of the trial and its open-label extension at 52 weeks compared the results in participants who started tofersen at trial entry (early-start cohort) with those in participants who switched from placebo to the drug at week 28 (delayed-start cohort). RESULTS A total of 72 participants received tofersen (39 predicted to have faster progression), and 36 received placebo (21 predicted to have faster progression). Tofersen led to greater reductions in concentrations of SOD1 in CSF and of neurofilament light chains in plasma than placebo. In the faster-progression subgroup (primary analysis), the change to week 28 in the ALSFRS-R score was -6.98 with tofersen and -8.14 with placebo (difference, 1.2 points; 95% confidence interval [CI], -3.2 to 5.5; P = 0.97). Results for secondary clinical end points did not differ significantly between the two groups. A total of 95 participants (88%) entered the open-label extension. At 52 weeks, the change in the ALSFRS-R score was -6.0 in the early-start cohort and -9.5 in the delayed-start cohort (difference, 3.5 points; 95% CI, 0.4 to 6.7); non-multiplicity-adjusted differences favoring early-start tofersen were seen for other end points. Lumbar puncture-related adverse events were common. Neurologic serious adverse events occurred in 7% of tofersen recipients. CONCLUSIONS In persons with SOD1 ALS, tofersen reduced concentrations of SOD1 in CSF and of neurofilament light chains in plasma over 28 weeks but did not improve clinical end points and was associated with adverse events. The potential effects of earlier as compared with delayed initiation of tofersen are being further evaluated in the extension phase. (Funded by Biogen; VALOR and OLE ClinicalTrials.gov numbers, NCT02623699 and NCT03070119; EudraCT numbers, 2015-004098-33 and 2016-003225-41.).
Having time to oneself in times of extended togetherness: Solitude experiences during the COVID-19 pandemic.

This study investigated how time to oneself (solitude) is experienced under conditions of extended togetherness with household members during the pandemic. Both structural (living arrangements) and qualitative characteristics (relationship quality and conflict) were examined for their association with solitude desire and daily solitude-affect links. We expected that people living with others and those with more high-quality as well as those with more conflictual relationships would report better affect quality when experiencing solitude. A Canadian adult lifespan sample (N = 141; Mage = 38.43 years, SDage = 17.51; 81% female; 73% White; data collected from April to August 2020) provided information on household size and relationship characteristics and completed repeated daily life assessments of solitude desire, solitude, and affect. Findings show that living arrangements were not associated with an increased desire for solitude or better affect quality from solitude. Individuals reporting higher relationship quality and individuals reporting more conflict showed more favorable affect quality on days when they had time in solitude than individuals reporting lower quality relationships and lower conflict. Findings add to the growing solitude literature by delineating who seeks and benefits from solitude, and under what conditions.
Proprioceptive contribution to oculomotor control in humans

Stretch receptors in the extraocular muscles (EOMs) inform the central nervous system about the rotation of one's own eyes in the orbits. Whereas fine control of the skeletal muscles hinges critically on proprioceptive feedback, the role of proprioception in oculomotor control remains unclear. Human behavioural studies provide evidence for EOM proprioception in oculomotor control, however, behavioural and electrophysiological studies in the macaque do not. Unlike macaques, humans possess numerous muscle spindles in their EOMs. To find out whether the human oculomotor nuclei respond to proprioceptive feedback we used functional magnetic resonance imaging (fMRI). With their eyes closed, participants placed their right index finger on the eyelid at the outer corner of the right eye. When prompted by a sound, they pushed the eyeball gently and briefly towards the nose. Control conditions separated out motor and tactile task components. The stretch of the right lateral rectus muscle was associated with activation of the left oculomotor nucleus and subthreshold activation of the left abducens nucleus. Because these nuclei control the horizontal movements of the left eye, we hypothesized that proprioceptive stimulation of the right EOM triggered left eye movement. To test this, we followed up with an eye‐tracking experiment in complete darkness using the same behavioural task as in the fMRI study. The left eye moved actively in the direction of the passive displacement of the right eye, albeit with a smaller amplitude. Eye tracking corroborated neuroimaging findings to suggest a proprioceptive contribution to ocular alignment.
Topics in gravitational dynamics : solar, extra-solar and galactic systems

An Overview on the Nekhoroshev Theorem. - Diffusion in Hamiltonian Quasi-Integrable Systems. - Weakly Dissipative Systems in Celestial Mechanics. - Connectance and Stability of Dynamical Systems. - Chaotic Di? usion of Asteroids. - An Overview of the Rotations of Planets in the Solar System. - On the Stability of Extra-Solar Planetary Systems. - Origin Theories for the Eccentricities of Extrasolar Planets. - Methods for the Study of the Dynamics of the Oort Cloud Comets I: Modelling the Stellar Perturbations. - Methods for the Study of the Dynamics of the Oort Cloud Comets II: Modelling the Galactic Tide. - Special Features of Galactic Dynamics. - On the Diffculty to Foresee Solar Cycles: A Non-Deterministic Approach.
A human STAT3 gain-of-function variant confers T cell dysregulation without predominant Treg dysfunction in mice

Primary immune regulatory disorders (PIRD) represent a group of disorders characterized by immune dysregulation, presenting with a wide range of clinical disease, including autoimmunity, autoinflammation, or lymphoproliferation. Autosomal dominant germline gain-of-function (GOF) variants in STAT3 result in a PIRD with a broad clinical spectrum. Studies in patients have documented a decreased frequency of FOXP3+ Tregs and an increased frequency of Th17 cells in some patients with active disease. However, the mechanisms of disease pathogenesis in STAT3 GOF syndrome remain largely unknown, and treatment is challenging. We developed a knock-in mouse model harboring a de novo pathogenic human STAT3 variant (p.G421R) and found these mice developed T cell dysregulation, lymphoproliferation, and CD4+ Th1 cell skewing. Surprisingly, Treg numbers, phenotype, and function remained largely intact; however, mice had a selective deficiency in the generation of iTregs. In parallel, we performed single-cell RNA-Seq on T cells from STAT3 GOF patients. We demonstrate only minor changes in the Treg transcriptional signature and an expanded, effector CD8+ T cell population. Together, these findings suggest that Tregs are not the primary driver of disease and highlight the importance of preclinical models in the study of disease mechanisms in rare PIRD.
High-order Multi-view Clustering for Generic Data

Graph-based multi-view clustering has achieved better performance than most non-graph approaches. However, in many real-world scenarios, the graph structure of data is not given or the quality of initial graph is poor. Additionally, existing methods largely neglect the high-order neighborhood information that characterizes complex intrinsic interactions. To tackle these problems, we introduce an approach called high-order multi-view clustering (HMvC) to explore the topology structure information of generic data. Firstly, graph filtering is applied to encode structure information, which unifies the processing of attributed graph data and non-graph data in a single framework. Secondly, up to infinity-order intrinsic relationships are exploited to enrich the learned graph. Thirdly, to explore the consistent and complementary information of various views, an adaptive graph fusion mechanism is proposed to achieve a consensus graph. Comprehensive experimental results on both non-graph and attributed graph data show the superior performance of our method with respect to various state-of-the-art techniques, including some deep learning methods.
Boosting as Frank-Wolfe

Some boosting algorithms, such as LPBoost, ERLPBoost, and C-ERLPBoost, aim to solve the soft margin optimization problem with the $\ell_1$-norm regularization. LPBoost rapidly converges to an $\epsilon$-approximate solution in practice, but it is known to take $\Omega(m)$ iterations in the worst case, where $m$ is the sample size. On the other hand, ERLPBoost and C-ERLPBoost are guaranteed to converge to an $\epsilon$-approximate solution in $O(\frac{1}{\epsilon^2} \ln \frac{m}{\nu})$ iterations. However, the computation per iteration is very high compared to LPBoost. To address this issue, we propose a generic boosting scheme that combines the Frank-Wolfe algorithm and any secondary algorithm and switches one to the other iteratively. We show that the scheme retains the same convergence guarantee as ERLPBoost and C-ERLPBoost. One can incorporate any secondary algorithm to improve in practice. This scheme comes from a unified view of boosting algorithms for soft margin optimization. More specifically, we show that LPBoost, ERLPBoost, and C-ERLPBoost are instances of the Frank-Wolfe algorithm. In experiments on real datasets, one of the instances of our scheme exploits the better updates of the secondary algorithm and performs comparably with LPBoost.