Miracle-dz/UniFAR-FTUs huggingface dataset:
Phenogenomic Characterization of a Newly Domesticated and Novel Species from the Genus Verrucosispora

The majority of environmental bacteria cannot be cultured within the laboratory. Understanding why only certain environmental isolates can be recovered is key to unlocking the abundant microbial dark matter that is widespread on our planet. ABSTRACT The concept of bacterial dark matter stems from our inability to culture most microbes and represents a fundamental gap in our knowledge of microbial diversity. Here, we present the domestication of such an organism: a previously uncultured, novel species from the rare Actinomycetes genus Verrucosispora. Although initial recovery took >4 months, isolation of phenotypically distinct, domesticated generations occurred within weeks. Two isolates were subjected to phenogenomic analyses, revealing domestication correlated with enhanced growth rates in nutrient-rich media but diminished capacity to metabolize diverse amino acids. This is seemingly mediated by genomic atrophy through a mixed approach of pseudogenization and reversion of pseudogenization of amino acid metabolism genes. Conversely, later generational strains had enhanced spore germination rates, potentially through the reversion of a sporulation-associated kinase from pseudogene to true gene status. We observed that our most wild-type isolate had the greatest potential for antibacterial activity, which correlated with extensive mutational attrition of biosynthetic gene clusters in domesticated strains. Comparative analyses revealed wholesale genomic reordering in strains, with widespread single nucleotide polymorphism, indel, and pseudogene-impactful mutations observed. We hypothesize that domestication of this previously unculturable organism resulted from the shedding of genomic flexibility required for life in a dynamic marine environment, parsing out genetic redundancy to allow for a newfound cultivable amenability. IMPORTANCE The majority of environmental bacteria cannot be cultured within the laboratory. Understanding why only certain environmental isolates can be recovered is key to unlocking the abundant microbial dark matter that is widespread on our planet. In this study, we present not only the culturing but domestication of just such an organism. Although initial recovery took >4 months, we were able to isolate distinct, subpassaged offspring from the originating colony within mere weeks. A phenotypic and genotypic analysis of our generational strains revealed that adaptation to life in the lab occurred as a result of wholesale mutational changes. These permitted an enhanced ability for growth in nutrient rich media but came at the expense of reduced genomic flexibility. We suggest that without dynamic natural environmental stressors our domesticated strains effectively underwent genomic atrophy as they adapted to static conditions experienced in the laboratory.
Future perspective: metabolism as a therapeutic target in acute myeloid leukemia – from Warburg to precision medicine

Abstract Acute myeloid leukemia (AML) is a highly malignant blood cancer disease, with dismal prognosis. The theory that cancer cells utilize metabolism to their growth advantage was postulated almost hundred years ago. However, only recently have been able to take advantage of this Achilles heel of malignant cell growth. Current observations suggest a crucial role for various metabolic pathways in AML, and special in leukemia stem cells, believed to be responsible for re-initiation of the leukemic clone, and hence relapse of this devastating disease. In the present article we discuss the features for metabolism in AML based on recent research, and special emphasizing the potential of pharmacological inhibiting metabolism as new treatment approaches.
High NAFLD fibrosis score in non-alcoholic fatty liver disease as a predictor of carotid plaque development: a retrospective cohort study based on regular health check-up data in China

Abstract Purposes There is increasing concern regarding cardiovascular risk in non-alcoholic fatty liver disease (NAFLD) patients with liver fibrosis. This study aims: (1) to assess the association between NAFLD and liver fibrosis status and the development of carotid plaque (CP), and (2) to identify CP risk factors among general population with different baseline NAFLD and liver fibrosis status. Methods This retrospective cohort study included 14,288 adult participants who went for regular health check-ups between 2014 and 2019, in one hospital in Zhejiang, China. NAFLD was diagnosed by abdominal ultrasound and the NAFLD fibrosis score (NFS) was calculated to reflect the extent of liver fibrosis. Cox proportional hazards analyses were applied to assess the risk of CP development across groups with different baseline NAFLD and NFS status. Results NAFLD participants with high NFS had higher risk of CP compared to non-NAFLD participants (adjusted hazard ratio 1.68, 95% confidence interval [CI] 1.43–1.96, p < .001). Progression from NAFLD free and NAFLD with low NFS to NAFLD with high NFS are associated with 1.56-fold (95% CI 1.21–2.01, p = .001) and 1.43-fold (95% CI 1.11-1.84, p = .006) increased risk of CP, respectively. Risk factors associated with CP vary based on baseline NAFLD and NFS status. Among NAFLD participants with high NFS, hypertension is the only significant risk factor after adjustment for other potential influencing factors. Conclusions NAFLD and liver fibrosis status can be an independent predictor for CP development regardless of metabolic abnormalities. Hypertension is a major risk factor for CP development among NAFLD patients with high NFS. KEY MESSAGES Non-alcoholic fatty liver disease (NAFLD) and liver fibrosis status can be an independent predictor for development of carotid plaque. Progression from NAFLD free and NAFLD with low NAFLD fibrosis score (NFS) to NAFLD with high NFS are associated with increased risk of carotid plaque. Risk factors associated with carotid plaque vary based on baseline NAFLD and NFS status, and hypertension plays the most important role among patients with NAFLD and high NFS.
Joint constraints on cosmology and the impact of baryon feedback: Combining KiDS-1000 lensing with the thermal Sunyaev-Zeldovich effect from Planck and ACT

We conduct a pseudo-$C_\ell$ analysis of the tomographic cross-correlation between 1000 deg$^2$ of weak lensing data from the Kilo-Degree Survey (KiDS-1000) and the thermal Sunyaev-Zeldovich (tSZ) effect measured by Planck and the Atacama Cosmology Telescope (ACT). Using HMx, a halo-model-based approach that consistently models the gas, star, and dark matter components, we are able to derive constraints on both cosmology and baryon feedback for the first time from these data, marginalising over redshift uncertainties, intrinsic alignment of galaxies, and contamination by the cosmic infrared background (CIB). We find our results to be insensitive to the CIB, while intrinsic alignment provides a small but significant contribution to the lensing--tSZ cross-correlation. The cosmological constraints are consistent with those of other low-redshift probes and prefer strong baryon feedback. The inferred amplitude of the lensing--tSZ cross-correlation signal, which scales as $\sigma_8(\Omega_\mathrm{m}/0.3)^{0.2}$, is low by $\sim 2\,\sigma$ compared to the primary cosmic microwave background constraints by Planck. The lensing--tSZ measurements are then combined with pseudo-$C_\ell$ measurements of KiDS-1000 cosmic shear into a novel joint analysis, accounting for the full cross-covariance between the probes, providing tight cosmological constraints by breaking parameter degeneracies inherent to both probes. The joint analysis gives an improvement of 40% on the constraint of $S_8=\sigma_8\sqrt{\Omega_\mathrm{m}/0.3}$ over cosmic shear alone, while providing constraints on baryon feedback consistent with hydrodynamical simulations, demonstrating the potential of such joint analyses with baryonic tracers such as the tSZ effect. We discuss remaining modelling challenges that need to be addressed if these baryonic probes are to be included in future precision-cosmology analyses.
Multi-granularity Textual Adversarial Attack with Behavior Cloning

Recently, the textual adversarial attack models become increasingly popular due to their successful in estimating the robustness of NLP models. However, existing works have obvious deficiencies. (1)They usually consider only a single granularity of modification strategies (e.g. word-level or sentence-level), which is insufficient to explore the holistic textual space for generation; (2) They need to query victim models hundreds of times to make a successful attack, which is highly inefficient in practice. To address such problems, in this paper we propose MAYA, a Multi-grAnularitY Attack model to effectively generate high-quality adversarial samples with fewer queries to victim models. Furthermore, we propose a reinforcement-learning based method to train a multi-granularity attack agent through behavior cloning with the expert knowledge from our MAYA algorithm to further reduce the query times. Additionally, we also adapt the agent to attack black-box models that only output labels without confidence scores. We conduct comprehensive experiments to evaluate our attack models by attacking BiLSTM, BERT and RoBERTa in two different black-box attack settings and three benchmark datasets. Experimental results show that our models achieve overall better attacking performance and produce more fluent and grammatical adversarial samples compared to baseline models. Besides, our adversarial attack agent significantly reduces the query times in both attack settings. Our codes are released at https://github.com/Yangyi-Chen/MAYA.
Establishment of trimester-specific reference intervals of serum lipids and the associations with pregnancy complications and adverse perinatal outcomes: a population-based prospective study

Abstract Background Disturbances in maternal lipid metabolism may increase the risk of developing pregnancy complications and adverse perinatal outcomes. However, there is no consensus as to what constitutes normal serum lipid ranges during pregnancy. Our study was aimed to establish trimester-specific serum lipid reference intervals (RIs) and investigate the associations between maternal dyslipidaemia and adverse outcomes in a population-based study. Methods The first- and third-trimester lipid profiles were derived from 16,489 singlet pregnant women for regular antenatal check-ups between 2017 and 2019. The serum samples were assayed for total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C) in the institutional clinical laboratory. The trimester-specific lipid RIs were estimated with both of the direct observational and the indirect Hoffmann methods. The associations between maternal lipid profiling and pregnancy complications and perinatal outcomes were assessed statistically. Results Serum levels of TC, TG, LDL-C and HDL-C were all increased significantly in the third trimester of pregnancy. There was no significant difference between the observed RIs established with healthy pregnant women and the calculated RIs derived from the Hoffmann method. A trend towards increased risks of gestational complications and adverse perinatal outcomes was observed in the subjects with elevated levels of TC, TG, and LDL-C or decreased level of HDL-C. Conclusions In pregnancy, increased serum levels of TC, TG and LDL-C, and a decreased level of HDL-C posed higher risks of developing pregnancy complications and adverse perinatal outcomes. Key messages It is necessary to establish trimester-specific reference intervals for serum lipids including TC, TG, LDL-C and HDL-C that were found significantly increased as the gestational age went up. More importantly, around the upper reference limits of TC, TG and LDL-C (or the lower reference limit of HDL-C), the higher the serum lipid levels were (or the lower the HDL-C level was), the higher risks of developing pregnancy complications and adverse perinatal outcomes were observed.
Attributing Fair Decisions with Attention Interventions

The widespread use of Artificial Intelligence (AI) in consequential domains, such as health-care and parole decision-making systems, has drawn intense scrutiny on the fairness of these methods. However, ensuring fairness is often insufficient as the rationale for a contentious decision needs to be audited, understood, and defended. We propose that the attention mechanism can be used to ensure fair outcomes while simultaneously providing feature attributions to account for how a decision was made. Toward this goal, we design an attention-based model that can be leveraged as an attribution framework. It can identify features responsible for both performance and fairness of the model through attention interventions and attention weight manipulation. Using this attribution framework, we then design a post-processing bias mitigation strategy and compare it with a suite of baselines. We demonstrate the versatility of our approach by conducting experiments on two distinct data types, tabular and textual.
Association between offensive and defensive playing style variables and ranking position in a national football league

ABSTRACT The aim of this study was to determine the association of playing style and efficacy variables with football success in a professional football league. Match statistics were obtained from 23 football teams competing in the 2017–2018 and 2018–2019 seasons of the Spanish national league(LaLiga). Offensive and defensive playing style and efficacy variables were calculated. Pearson’s correlation coefficient tests and principal component analysis (PCA) were applied to establish the influence of these variables on the number of points obtained at the end of the season and on the ranking position. In isolation, the efficacy of completion showed the highest association with ranking points and position. A two-dimension PCA explained 77.8% of the variance in the ranking position. In dimension-1 (58.5%), game initiative and attack building, and in dimension-2 (19.3%), efficacy of defensive containment and a lower rate of long passes were within the variables that explained more variance in the ranking position. Success in football, measured by ranking position at the end of the Spanish national league, was associated with several playing style and efficacy variables. Overall, a dominant game style with high efficacy to finish attacking plays, and an offensive game initiative, are most associated with successful football.
Febuxostat ameliorates high salt intake-induced hypertension and renal damage in Dahl salt-sensitive rats

Objective: Several clinical studies have reported that xanthine oxidoreductase inhibitors have antihypertensive and renal protective effects but their mechanisms have not been fully determined. This study aims to clarify these mechanisms by examining the effects of febuxostat, which is a novel selective xanthine oxidoreductase inhibitor, in Dahl salt-sensitive rats. Methods: Eight-week-old male Dahl salt-sensitive rats were fed a normal salt (0.6% NaCl) or high salt (8% NaCl) diet for 8 weeks. A portion of the rats that were fed high salt diet were treated with febuxostat (3 mg/kg per day) simultaneously. Additionally, acute effects of febuxostat (3 mg/kg per day) were examined after high salt diet feeding for 4 or 8 weeks. Results: Treatment with febuxostat for 8 weeks attenuated high salt diet-induced hypertension, renal dysfunction, glomerular injury, and renal interstitial fibrosis. Febuxostat treatment reduced urinary excretion of H2O2 and malondialdehyde and renal thiobarbituric acid reactive substances content. High salt diet increased xanthine oxidoreductase activity and expression in the proximal tubules and medullary interstitium. Febuxostat completely inhibited xanthine oxidoreductase activity and attenuated the high salt diet-increased xanthine oxidoreductase expression. Febuxostat transiently increased urine volume and Na+ excretion without change in blood pressure or urinary creatinine excretion after high salt diet feeding for 4 or 8 weeks. Conclusion: Febuxostat ameliorates high salt diet-induced hypertension and renal damage with a reduction of renal oxidative stress in Dahl salt-sensitive rats. The antihypertensive effect of febuxostat may be mediated in part by diuretic and natriuretic action.
Primary mediastinal Large B-cell Lymphoma.

Primary mediastinal large B-cell lymphoma (PMBCL) is a separate entity in the WHO classification based on clinico-pathologic features and a distinct molecular signature which overlaps with nodular sclerosis classical Hodgkin lymphoma (NScHL). Molecular classifiers can distinguish PMBCL from diffuse large B-cell lymphoma (DLBCL) using RNA derived from paraffin-embedded tissue and are integral to future studies. However, given that ~5% of DLBCL can have a 'molecular' PMBCL phenotype in the absence of mediastinal involvement, clinical information will remain critical for diagnosis. Studies over the last 10-20 years have elucidated the biologic hallmarks of PMBCL which are reminiscent of cHL, including the importance of JAK-STAT and NFKB signaling pathways as well as an immune evasion phenotype through multiple converging genetic aberrations. The outcome of PMBCL has improved in the modern rituximab era, however controversies remain whether there is a single standard treatment for all patients and when to integrate radiotherapy. Regardless of the frontline therapy, refractory disease can occur in up to 10% of patients and correlates with poor outcome. With emerging data supporting high efficacy of PD1 inhibitors in PMBCL, studies are underway integrating them into the up-front setting.
Digital Rehabilitation for Acute Ankle Sprains: Prospective Longitudinal Cohort Study

Background Ankle sprains are one of the most prevalent soft-tissue injuries worldwide. Physical therapy, especially progressive exercise, has proven effective in improving function, while preventing recurrence. Objective We aim to present the results of a fully remote and digitally guided rehabilitation program for acute ankle sprains. Methods We performed a prospective longitudinal cohort study of individuals eligible for workers’ compensation, who were referred for digital rehabilitation therapy for a sprained ankle. Therapeutic exercise sessions were to be performed independently by the patient at home using the biofeedback device provided by SWORD Health. Primary endpoints were the change in self-reported Numerical Pain Rating Scale (NPRS) and Foot and Ankle Ability Measure–activities of daily living (FAAM–ADL) and FAAM–Sports scores. Participants were assessed at baseline, end of the program, and 6 months after program completion. Secondary outcomes included digital therapy dosage, pain and fatigue during sessions, and satisfaction. Results In total, 93 (89.4%) patients completed the program and 79 (76.0%) were available for follow-up. Changes in the primary outcomes between baseline and the 6-month follow-up were both significant (P<.001) and clinically meaningful: mean difference of –2.72 points (95% CI –3.31 to –2.13) on the NPRS (49.8% reduction), 21.7 points (95% CI 17.13-26.27) on the FAAM–ADL (41.1% increase), and 37.8 points (95% CI 30.45-45.15) on the FAAM-Sports (151.8% increase). Longer waiting periods between the accident date and treatment initiation were found to negatively impact functional status at baseline and at the end of the program, triggering an extension in the program duration. The total training volume (12.5 hours, SD 10.5 hours) was similar to that of other interventions for ankle sprains, but the dosage per week was much higher (2.4 hours per week, SD 0.87 hours per week). The mean patient satisfaction score was 8.8 (SD 1.57) out of 10. Among program completers, 83.9% attained full recovery and were discharged with no residual disability. Conclusions Being far less demanding in terms of human resources, the digital program presented constituted a viable, clinically effective, and convenient solution for ankle sprain rehabilitation, particularly during the pandemic. This is the first study presenting a fully remote home-based rehabilitation program for acute ankle sprains, with patients achieving sustained long-term results. This was a prospective cohort study and, as such, did not include a control group, but the results appear comparable to those published for face-to-face interventions. Trial Registration ClinicalTrials.gov NCT04819022; https://clinicaltrials.gov/ct2/show/NCT04819022
Cycling in a crowd: Coordination of plant cell division, growth, and cell fate

Abstract The reiterative organogenesis that drives plant growth relies on the constant production of new cells, which remain encased by interconnected cell walls. For these reasons, plant morphogenesis strictly depends on the rate and orientation of both cell division and cell growth. Important progress has been made in recent years in understanding how cell cycle progression and the orientation of cell divisions are coordinated with cell and organ growth and with the acquisition of specialized cell fates. We review basic concepts and players in plant cell cycle and division, and then focus on their links to growth-related cues, such as metabolic state, cell size, cell geometry, and cell mechanics, and on how cell cycle progression and cell division are linked to specific cell fates. The retinoblastoma pathway has emerged as a major player in the coordination of the cell cycle with both growth and cell identity, while microtubule dynamics are central in the coordination of oriented cell divisions. Future challenges include clarifying feedbacks between growth and cell cycle progression, revealing the molecular basis of cell division orientation in response to mechanical and chemical signals, and probing the links between cell fate changes and chromatin dynamics during the cell cycle.
Validation of grooved pegboard cutoffs as an additional embedded measure of performance validity

Abstract Objective Using embedded performance validity (PVT) comparisons, Erdodi et al. suggested that Grooved Pegboard (GPB) T-score cutoffs for either hand ( 29) or both hands ( 31) could be used as additional embedded PVTs. The current study evaluated the relationship between these proposed cutoff scores and established PVTs (Medical Symptom Validity Test [MSVT]; Non-Verbal Medical Symptom Validity Test [NV-MSVT], and Reliable Digit Span [RDS]). Method Participants (N = 178) were predominately Caucasian (84%) males (79%) with a mean age and education of 41 (SD = 11.7) and 15.8 years (SD = 2.3), respectively. Participants were stratified as “passing” or “failing” the GPBviaErdodi’s proposed criteria. “Failures” on the MSVT, NV-MSVT, and RDS were based on conventional recommendations. Results Moderate correlations between GPB classification and a condition of interest (COI; i.e. at least two failures on reference PVTs) were observed for dominant (χ2 (1, n = 178) = 34.72, ϕ = . 44, p < . 001), non-dominant (χ2 (1, n = 178) = 16.46, ϕ = . 30, p = . 001), and both hand conditions (χ2 (1, n = 178) = 32.48, ϕ = . 43, p < . 001). Sensitivity, specificity, and predictive power were generally higher than Erdodi et al.’s initial findings. Conclusion These findingsprovide supportfor the clinical utility of the GPB as an additional embedded PVT. More specifically, dominant and both hand cutoffs were found to be more robust measures ofnon-genuine performance in those without motor deficits. While promising, sensitivity continues to be low; therefore, it is ill-advised to use the GPB as a sole measure of performance validity.