Miracle-dz/UniFAR-FTUs huggingface dataset:
Diverse Online Feature Selection

Online feature selection has been an active research area in recent years. We propose a novel diverse online feature selection method based on Determinantal Point Processes (DPP). Our model aims to provide diverse features which can be composed in either a supervised or unsupervised framework. The framework aims to promote diversity based on the kernel produced on a feature level, through at most three stages: feature sampling, local criteria and global criteria for feature selection. In the feature sampling, we sample incoming stream of features using conditional DPP. The local criteria is used to assess and select streamed features (i.e. only when they arrive), we use unsupervised scale invariant methods to remove redundant features and optionally supervised methods to introduce label information to assess relevant features. Lastly, the global criteria uses regularization methods to select a global optimal subset of features. This three stage procedure continues until there are no more features arriving or some predefined stopping condition is met. We demonstrate based on experiments conducted on that this approach yields better compactness, is comparable and in some instances outperforms other state-of-the-art online feature selection methods.
Impact of Hypothyroidism and Heart Failure on Hospitalization Risk.

BACKGROUND Prior studies suggest that the relationship between hypothyroidism and mortality is dependent on underlying cardiovascular risk. Little is known about the association of hypothyroidism with hospitalization risk, and how these associations are modified by cardiovascular status. METHODS This study examined the association of thyroid status, defined by serum thyrotropin (TSH), with hospitalization risk among patients who received care at a large university-based tertiary care center between 1990 and 2015. Thyroid status was categorized as hypothyroidism versus euthyroidism (TSH >4.7 vs. 0.3-4.7 mIU/L, respectively). The relationship between thyroid status and hospitalization risk stratified by cardiovascular status was examined using multivariable Cox models. RESULTS Among 52,856 patients who met eligibility criteria, 49,791 (94.2%) had euthyroidism and 3065 (5.8%) had hypothyroidism. In analyses stratified by congestive heart failure (CHF) status, compared to euthyroidism, hypothyroidism was associated with higher risk of hospitalization in those with CHF but slightly lower risk in those without CHF (adjusted hazard ratio [aHRs] = 1.86 [confidence interval (CI) 1.17-2.94] and HR = 0.95 [CI 0.92-0.99], respectively; p = 0.006). In sensitivity analyses accounting for death as a competing event, underlying coronary artery disease modified the hypothyroidism-hospitalization relationship, such that stronger associations were observed among those with versus without coronary artery disease. In competing risk analyses, hypothyroidism was associated with higher versus lower risk of hospitalization among those with versus without cerebrovascular disease, respectively. CONCLUSIONS Hypothyroidism is associated with higher hospitalization risk among patients with underlying cardiovascular disease. Future studies are needed to determine whether correction of thyroid status with replacement therapy ameliorates hospitalization risk in this population.
Understanding the Agility of Running Birds: Sensorimotor and Mechanical Factors in Avian Bipedal Locomotion

Abstract Birds are a diverse and agile lineage of vertebrates that all use bipedal locomotion for at least part of their life. Thus birds provide a valuable opportunity to investigate how biomechanics and sensorimotor control are integrated for agile bipedal locomotion. This review summarizes recent work using terrain perturbations to reveal neuromechanical control strategies used by ground birds to achieve robust, stable, and agile running. Early experiments in running guinea fowl aimed to reveal the immediate intrinsic mechanical response to an unexpected drop (“pothole”) in terrain. When navigating the pothole, guinea fowl experience large changes in leg posture in the perturbed step, which correlates strongly with leg loading and perturbation recovery. Analysis of simple theoretical models of running has further confirmed the crucial role of swing-leg trajectory control for regulating foot contact timing and leg loading in uneven terrain. Coupling between body and leg dynamics results in an inherent trade-off in swing leg retraction rate for fall avoidance versus injury avoidance. Fast leg retraction minimizes injury risk, but slow leg retraction minimizes fall risk. Subsequent experiments have investigated how birds optimize their control strategies depending on the type of perturbation (pothole, step, obstacle), visibility of terrain, and with ample practice negotiating terrain features. Birds use several control strategies consistently across terrain contexts: (1) independent control of leg angular cycling and leg length actuation, which facilitates dynamic stability through simple control mechanisms, (2) feedforward regulation of leg cycling rate, which tunes foot-contact timing to maintain consistent leg loading in uneven terrain (minimizing fall and injury risks), (3) load-dependent muscle actuation, which rapidly adjusts stance push-off and stabilizes body mechanical energy, and (4) multi-step recovery strategies that allow body dynamics to transiently vary while tightly regulating leg loading to minimize risks of fall and injury. In future work, it will be interesting to investigate the learning and adaptation processes that allow animals to adjust neuromechanical control mechanisms over short and long timescales.
Impact of acute versus prolonged exercise and dehydration on kidney function and injury

Exercise and dehydration may be associated with a compromised kidney function and potential signs of kidney injury. However, the kidney responses to exercise of different durations and hypohydration levels are not yet known. Therefore, we aimed to compare the effects of acute versus prolonged exercise and dehydration on estimated glomerular filtration rate (eGFR) and kidney injury biomarkers in healthy male adults. A total of 35 subjects (23 ± 3 years) were included and invited for two study visits. Visit 1 consisted of a maximal cycling test. On Visit 2, subjects performed a submaximal exercise test at 80% of maximal heart rate until 3% hypohydration. Blood and urine samples were taken at baseline, after 30 min of exercise (acute effects; low level of hypohydration) and after 150 min of exercise or when 3% hypohydration was achieved (prolonged effects, high level of hypohydration). Urinary outcome parameters were corrected for urinary cystatin C, creatinine, and osmolality. Subjects dehydrated on average 0.6 ± 0.3% and 2.9 ± 0.7% after acute and prolonged exercise, respectively (P < 0.001). The eGFRcystatin C did not differ between baseline and acute exercise (118 ± 11 vs. 116 ± 12 mL/min/1.73 m2, P = 0.12), whereas eGFRcystatin C was significantly lower after prolonged exercise (103 ± 16 mL/min/1.73 m2, P < 0.001). We found no difference in osmolality corrected uKIM1 concentrations after acute and prolonged exercise (P > 0.05), and elevated osmolality corrected uNGAL concentrations after acute and prolonged exercise (all P‐values < 0.05). In conclusion, acute exercise did barely impact on eGFRcystatin C and kidney injury biomarkers, whereas prolonged exercise is associated with a decline in eGFRcystatin C and increased biomarkers for kidney injury.
Bachelor Degree Project Automated classification of bibliographic data using SVM and Naive Bayes

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High‐affinity PD‐1 molecules deliver improved interaction with PD‐L1 and PD‐L2

The inhibitory checkpoint molecule programmed death (PD)‐1 plays a vital role in maintaining immune homeostasis upon binding to its ligands, PD‐L1 and PD‐L2. Several recent studies have demonstrated that soluble PD‐1 (sPD‐1) can block the interaction between membrane PD‐1 and PD‐L1 to enhance the antitumor capability of T cells. However, the affinity of natural sPD‐1 binding to PD‐L1 is too low to permit therapeutic applications. Here, a PD‐1 variant with approximately 3000‐fold and 70‐fold affinity increase to bind PD‐L1 and PD‐L2, respectively, was generated through directed molecular evolution and phage display technology. Structural analysis showed that mutations at amino acid positions 124 and 132 of PD‐1 played major roles in enhancing the affinity of PD‐1 binding to its ligands. The high‐affinity PD‐1 mutant could compete with the binding of antibodies specific to PD‐L1 or PD‐L2 on cancer cells or dendritic cells, and it could enhance the proliferation and IFN‐γ release of activated lymphocytes. These features potentially qualify the high‐affinity PD‐1 variant as a unique candidate for the development of a new class of PD‐1 immune‐checkpoint blockade therapeutics.
A new method for predicting essential proteins based on participation degree in protein complex and subgraph density

Essential proteins are crucial to living cells. Identification of essential proteins from protein-protein interaction (PPI) networks can be applied to pathway analysis and function prediction, furthermore, it can contribute to disease diagnosis and drug design. There have been some experimental and computational methods designed to identify essential proteins, however, the prediction precision remains to be improved. In this paper, we propose a new method for identifying essential proteins based on Participation degree of a protein in protein Complexes and Subgraph Density, named as PCSD. In order to test the performance of PCSD, four PPI datasets (DIP, Krogan, MIPS and Gavin) are used to conduct experiments. The experiment results have demonstrated that PCSD achieves a better performance for predicting essential proteins compared with some competing methods including DC, SC, EC, IC, LAC, NC, WDC, PeC, UDoNC, and compared with the most recent method LBCC, PCSD can correctly predict more essential proteins from certain numbers of top ranked proteins on the DIP dataset, which indicates that PCSD is very effective in discovering essential proteins in most case.
Correlation between Sex and Prognosis of Acute Aortic Dissection in the Chinese Population

Background: The prevalence, presentation, management, and prognosis of coronary heart disease differ according to sex. Greater understanding on the differences between men and women with acute aortic dissection (AAD) is needed. We aimed to investigate whether sex disparities are found in patients with AAD, and to study sex differences in complications, mortality in-hospital, and long-term. Methods: We included 884 patients enrolled in our institute between June 2002 and May 2016. Considering psychosocial factors, treatments, and the outcomes in men versus those in women with AAD, we explored the association of sex with psychosocial characteristics and mortality risk. For categorical variables, significant differences between groups were assessed with the Chi-square test or Fisher's exact test, and continuous parameters were assessed with Student's t-test. Univariate and stratified survival statistics were computed using Kaplan-Meier analysis. Results: A total of 884 patients (76.1% male, mean age 51.4 ± 11.8 years) were included in this study. There were fewer current smokers in female compared with male (17.5% vs. 67.2%, &khgr;2 = 160.06, P < 0.05). The percentage of men who reported regular alcohol consumption was significantly higher than that in women (40.6% vs. 3.8%, &khgr;2 = 100.18, P < 0.05). About 6.2% (55 of 884) of patients with AAD died before vascular or endovascular surgery was performed, 34.4% (304 of 884) of patients underwent surgical procedures, and 52.7% (466 of 884) and 12.8% (113 of 884) of patients received endovascular treatment and medication. Postoperative mortality similar (6.0% vs. 5.6%, respectively, &khgr;2 = 0.03, P = 0.91) between men and women. Follow-up was completed in 653 of 829 patients (78.8%). Adjustment for age, history of coronary disease, hypertension, smoking and drinking, Type A and use of beta-blocker, angiotensin II receptor blockers, angiotensin converting enzyme (ACE) inhibitor, calcium-channel blockers and statins by multivariate logistic regression analysis suggested that age (odds ratios [ORs], 1.04; 95% confidence interval [CI], 1.01–1.07; P < 0.05), using of calcium-channel blockers (OR, 0.37; 95% CI, 0.18–0.74; P < 0.05), at discharge were independent predictors of late mortality, ACE inhibitors (OR, 1.91; 95% CI, 1.03–3.54; P = 0.04) was independent risk factor of late mortality. Conclusions: In Chinese with AAD, sex is not independently associated with long-term clinical outcomes. Age, the intake of calcium-channel blockers at discharge might help to improve long-term outcomes.
CRISPR base editors: genome editing without double-stranded breaks

The CRISPR (clustered regularly interspaced short palindromic repeat)/Cas9 adaptive immunity system has been harnessed for genome editing applications across eukaryotic species, but major drawbacks, such as the inefficiency of precise base editing and off-target activities, remain. A catalytically inactive Cas9 variant (dead Cas9, dCas9) has been fused to diverse functional domains for targeting genetic and epigenetic modifications, including base editing, to specific DNA sequences. As base editing does not require the generation of double-strand breaks, dCas9 and Cas9 nickase have been used to target deaminase domains to edit specific loci. Adenine and cytidine deaminases convert their respective nucleotides into other DNA bases, thereby offering many possibilities for DNA editing. Such base-editing enzymes hold great promise for applications in basic biology, trait development in crops, and treatment of genetic diseases. Here, we discuss recent advances in precise gene editing using different platforms as well as their potential applications in basic biology and biotechnology.
Staphylococcus pseudintermedius biofilms secrete factors that induce inflammatory reactions in vitro

Biofilms, composed of bacterial cells embedded in a secreted polysaccharide and protein matrix, often cause problems such as chronic and refractory infections. Staphylococcus pseudintermedius, which is an important pathogen in veterinary medicine, has a high rate of biofilm production. Although it is considered that S. pseudintermedius biofilms are associated with prolonged inflammatory disorders, there are no reports that S. pseudintermedius biofilm directly regulates inflammatory reactions. In this study, we focused on the metabolites derived from biofilm cultures of S. pseudintermedius and evaluated their inflammatory effects in vitro. Expression levels of interleukin‐1 beta and interleukin‐6 mRNA significantly increased in RAW264.7 cells that were cultured with biofilm‐conditioned medium (BCM). The secreted proteins in BCM were heat resistance and activated a Toll‐like receptor (TLR) signalling pathway. Moreover, based on SDS‐PAGE analysis, isolates with stronger biofilm‐forming capabilities induced more inflammatory reactions and had specific banding patterns compared with those of weak biofilm producers. Collectively, our results suggest that the proteins derived from S. pseudintermedius biofilm induce a host inflammatory response via a TLR pathway. Furthermore, the severity of inflammation depends on the biofilm formation capacity of the S. pseudintermedius strain.
Multifactorial control of the expression of a CRISPR-Cas system by an extracytoplasmic function σ/anti-σ pair and a global regulatory complex

Abstract Expression of CRISPR-Cas systems is a prerequisite for their defensive role against invading genetic elements. Yet, much remains unknown about how this crucial step is regulated. We describe a new mechanism controlling CRISPR-cas expression, which requires an extracytoplasmic function (ECF) σ factor (DdvS), its membrane-bound anti-σ (DdvA) and a global regulatory complex (CarD–CarG). Transcriptomic analyses revealed that the DdvS/CarD/CarG-dependent regulon comprises a type III-B CRISPR-Cas system in Myxococcus xanthus. We mapped four DdvS-driven CarD/CarG-dependent promoters, with one lying immediately upstream of the cas cluster. Consistent with direct action, DdvS and CarD–CarG localize at these promoters in vivo. The cas genes are transcribed as a polycistronic mRNA that reads through the leader into the CRISPR array, a putative σA-dependent promoter in the leader having negligible activity in vivo. Consequently, expression of the entire CRISPR-Cas system and mature CRISPR-RNA (crRNA) production is DdvS/CarD/CarG-dependent. DdvA likely uses its large C-terminal domain to sense and transduce the extracytoplasmic signal triggering CRISPR-cas expression, which we show is not starvation-induced multicellular development. An ECF-σ/anti-σ pair and a global regulatory complex provide an effective mechanism to coordinate signal-sensing with production of precursor crRNA, its processing Cas6 endoribonuclease and other Cas proteins for mature crRNA biogenesis and interference.
Strategic networks and new product performance: the mediating role of ambidextrous innovation

ABSTRACT In this study we examine the relationship between strategic networks and new product performance from the perspective of ambidextrous innovation (i.e. combining exploratory innovation and exploitative innovation) using a sample of 323 manufacturing firms in the transitional economy of China. Our empirical analyses present several interesting findings: (a) strategic networks are positively related to firms’ new product performance; (b) ambidextrous innovation has a positive effect on firms’ new product performance – that is, the combination of exploratory innovation and exploitative innovation positively affects the firm's new product performance, while the lack of balance between exploratory innovation and exploitative innovation negatively affects the firm's new product performance; and (c) ambidextrous innovation mediates the relationship between strategic networks and new product performance. Our findings provide scholars and managers with a better understanding of the key role played by the simultaneous adoption of exploratory and exploitative innovation in the relationship between strategic networks and new product performance.
Cutibacterium acnes (Propionibacterium acnes) and acne vulgaris: a brief look at the latest updates

While the commensal bacterium Propionibacterium acnes (P. acnes) is involved in the maintenance of a healthy skin, it can also act as an opportunistic pathogen in acne vulgaris. The latest findings on P. acnes shed light on the critical role of a tight equilibrium between members of its phylotypes and within the skin microbiota in the development of this skin disease. Indeed, contrary to what was previously thought, proliferation of P. acnes is not the trigger of acne as patients with acne do not harbour more P. acnes in follicles than normal individuals. Instead, the loss of the skin microbial diversity together with the activation of the innate immunity might lead to this chronic inflammatory condition. This review provides results of the most recent biochemical and genomic investigations that led to the new taxonomic classification of P. acnes renamed Cutibacterium acnes (C. acnes), and to the better characterisation of its phylogenetic cluster groups. Moreover, the latest data on the role of C. acnes and its different phylotypes in acne are presented, providing an overview of the factors that could participate in the virulence and in the antimicrobial resistance of acne‐associated strains. Overall, this emerging key information offers new perspectives in the treatment of acne, with future innovative strategies focusing on C. acnes biofilms and/or on its acne‐associated phylotypes.
A noncanonical PPARγ/RXRα-binding sequence regulates leptin expression in response to changes in adipose tissue mass

Significance Leptin gene expression is highly correlated with the lipid content of individual fat cells, suggesting that it is regulated by a “fat-sensing” signal transduction pathway. This possibility is thus analogous to the identification of a cholesterol-sensing pathway by studying the regulation of the LDL receptor gene by intracellular cholesterol. Several lines of investigation have suggested that, in addition to adipocytes, liver, neurons, and other cell types can sense changes in lipid content, although the molecular mechanisms are unknown. The data here provide a critical step toward elucidating the components of this putative system, which would be of great importance. These studies also identify a previously underappreciated role of the PPARγ/RXRα complex to regulate leptin expression. Leptin expression decreases after fat loss and is increased when obesity develops, and its proper quantitative regulation is essential for the homeostatic control of fat mass. We previously reported that a distant leptin enhancer 1 (LE1), 16 kb upstream from the transcription start site (TSS), confers fat-specific expression in a bacterial artificial chromosome transgenic (BACTG) reporter mouse. However, this and the other elements that we identified do not account for the quantitative changes in leptin expression that accompany alterations of adipose mass. In this report, we used an assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) to identify a 17-bp noncanonical peroxisome proliferator-activated receptor gamma (PPARγ)/retinoid X receptor alpha (RXRα)-binding site, leptin regulatory element 1 (LepRE1), within LE1, and show that it is necessary for the fat-regulated quantitative control of reporter (luciferase) expression. While BACTG reporter mice with mutations in this sequence still show fat-specific expression, luciferase is no longer decreased after food restriction and weight loss. Similarly, the increased expression of leptin reporter associated with obesity in ob/ob mice is impaired. A functionally analogous LepRE1 site is also found in a second, redundant DNA regulatory element 13 kb downstream of the TSS. These data uncouple the mechanisms conferring qualitative and quantitative expression of the leptin gene and further suggest that factor(s) that bind to LepRE1 quantitatively control leptin expression and might be components of a lipid-sensing system in adipocytes.
TGF-β in T Cell Biology: Implications for Cancer Immunotherapy

Transforming Growth Factor beta (TGF-β) is a pleiotropic cytokine produced in large amounts within cancer microenvironments that will ultimately promote neoplastic progression, notably by suppressing the host’s T-cell immunosurveillance. This effect is mostly due to the well-known inhibitory effect of TGF-β on T cell proliferation, activation, and effector functions. Moreover, TGF-β subverts T cell immunity by favoring regulatory T-cell differentiation, further reinforcing immunosuppression within tumor microenvironments. These findings stimulated the development of many strategies to block TGF-β or its signaling pathways, either as monotherapy or in combination with other therapies, to restore anti-cancer immunity. Paradoxically, recent studies provided evidence that TGF-β can also promote differentiation of certain inflammatory populations of T cells, such as Th17, Th9, and resident-memory T cells (Trm), which have been associated with improved tumor control in several models. Here, we review current advances in our understanding of the many roles of TGF-β in T cell biology in the context of tumor immunity and discuss the possibility to manipulate TGF-β signaling to improve cancer immunotherapy.