Miracle-dz/UniFAR-FTUs huggingface dataset:
Cold-Start Active Sampling Via γ-Tube

Active learning (AL) improves the generalization performance for the current classification hypothesis by querying labels from a pool of unlabeled data. The sampling process is typically assessed by an informative, representative, or diverse evaluation policy. However, the policy, which needs an initial labeled set to start, may degenerate its performance in a <italic>cold-start</italic> hypothesis. In this article, we first show that typical AL sampling can be equivalently formulated as geometric sampling over minimum enclosing ballsMEB of this article denotes a conceptual geometry over the cluster in generalization analysis. In the SVM community, it is related to hard-margin support vector data description. (MEBs) of clusters. Following the <inline-formula> <tex-math notation="LaTeX">$\gamma $ </tex-math></inline-formula>-tube structure in geometric clustering, we then divide one MEB covering a cluster into two parts: 1) a <inline-formula> <tex-math notation="LaTeX">$\gamma $ </tex-math></inline-formula>-tube and 2) a <inline-formula> <tex-math notation="LaTeX">$\gamma $ </tex-math></inline-formula>-ball. By estimating the error disagreement between sampling in MEB and <inline-formula> <tex-math notation="LaTeX">$\gamma $ </tex-math></inline-formula>-ball, our theoretical insight reveals that <inline-formula> <tex-math notation="LaTeX">$\gamma $ </tex-math></inline-formula>-tube can effectively measure the disagreement of hypotheses in original space over MEB and sampling space over <inline-formula> <tex-math notation="LaTeX">$\gamma $ </tex-math></inline-formula>-ball. To tighten our insight, we present generalization analysis, and the results show that sampling in <inline-formula> <tex-math notation="LaTeX">$\gamma $ </tex-math></inline-formula>-tube can derive higher probability bound to achieve a nearly zero generalization error. With these analyses, we finally apply the informative sampling policy of AL over <inline-formula> <tex-math notation="LaTeX">$\gamma $ </tex-math></inline-formula>-tube to present a tube AL (TAL) algorithm against the cold-start sampling issue. As a result, the dependency between the querying process and the evaluation policy of active sampling can be alleviated. Experimental results show that by using the <inline-formula> <tex-math notation="LaTeX">$\gamma $ </tex-math></inline-formula>-tube structure to deal with cold-start sampling, TAL achieves the superior performance than standard AL evaluation baselines by presenting substantial accuracy improvements. Image edge recognition extends our theoretical results.
Evaluation of antityrosinase activity and mechanism, antioxidation, and UV filter properties of theaflavin

Tyrosinase is a key metalloenzyme for the biosynthesis of melanin that plays a critical role in the prevention of skin damage caused by ultraviolet (UV) radiation. However, the overproduction of melanin may cause a variety of skin diseases. Due to the toxicity and inefficiency of existing tyrosinase inhibitors, it is urgent to identify safe and potent alternatives from natural sources. Theaflavin, a single‐component extracted from black tea, has been found to possess a variety of pharmacological activities. Herein, the inhibition kinetics of theaflavin on tyrosinase and inhibitory mechanism were determined using spectroscopy, molecular docking, and zebrafish model. The results showed that theaflavin inhibited the diphenolase activity of tyrosinase in a reversible mixed type manner with IC50 of 229.75 μmol/L and hindered the synthesis of melanin in zebrafish. This may be due to the formation of eight hydrogen bonds and hydrophobic effects between theaflavin and tyrosinase according to the results of molecular docking. To study the possible effects on the prevention of free radical‐mediated skin cancer and photoaging caused by UV radiation, the antioxidation and UV filter properties of theaflavin were further verified. This study demonstrates that theaflavin is a potential multifunctional compound that can be used in cosmetic and medicinal products.
Perivascular Macrophages Regulate Blood Flow Following Tissue Damage

Supplemental Digital Content is available in the text. Rationale: Ischemic injuries remain a leading cause of mortality and morbidity worldwide, and restoration of functional blood perfusion is vital to limit tissue damage and support healing. Objective: To reveal a novel role of macrophages in reestablishment of functional tissue perfusion following ischemic injury that can be targeted to improve tissue restoration. Methods and Results: Using intravital microscopy of ischemic hindlimb muscle in mice, and confocal microscopy of human tissues from amputated legs, we found that macrophages accumulated perivascularly in ischemic muscles, where they expressed high levels of iNOS (inducible nitric oxide [NO] synthase). Genetic depletion of iNOS specifically in macrophages (Cx3cr1-CreERT2;Nos2fl/fl or LysM-Cre;Nos2fl/fl) did not affect vascular architecture but highly compromised blood flow regulation in ischemic but not healthy muscle, which resulted in aggravated ischemic damage. Thus, the ability to upregulate blood flow was shifted from eNOS (endothelial)-dependence in healthy muscles to completely rely on macrophage-derived iNOS during ischemia. Macrophages in ischemic muscles expressed high levels of CXCR4 (C-X-C chemokine receptor type 4) and CCR2 (C-C chemokine receptor type 2), and local overexpression by DNA plasmids encoding the corresponding chemokines CXCL12 (stromal-derived factor 1) or CCL2 (chemokine [C-C motif] ligand 2) increased macrophage numbers, while CXCL12 but not CCL2 induced their perivascular positioning. As a result, CXCL12-overexpression increased the number of perfused blood vessels in the ischemic muscles, improved functional muscle perfusion in a macrophage-iNOS-dependent manner, and ultimately restored limb function. Conclusions: This study establishes a new function for macrophages during tissue repair, as they regulate blood flow through the release of iNOS-produced NO. Further, we demonstrate that macrophages can be therapeutically targeted to improve blood flow regulation and functional recovery of ischemic tissues.
The Structural and Electrophysiological Properties of Progesterone Receptor-Expressing Neurons Vary along the Anterior-Posterior Axis of the Ventromedial Hypothalamus and Undergo Local Changes across the Reproductive Cycle

Visual Abstract Sex hormone levels continuously fluctuate across the reproductive cycle, changing the activity of neuronal circuits to coordinate female behavior and reproductive capacity. The ventrolateral division of the ventromedial hypothalamus (VMHvl) contains neurons expressing receptors for sex hormones and its function is intimately linked to female sexual receptivity. However, recent findings suggest that the VMHvl is functionally heterogeneous. Here, we used whole recordings and intracellular labeling to characterize the electrophysiological and morphologic properties of individual VMHvl neurons in naturally cycling females and report the existence of multiple electrophysiological phenotypes within the VMHvl. We found that the properties of progesterone receptor expressing (PR+) neurons, but not PR– neurons, depended systematically on the neuron’s location along the anterior-posterior (AP) axis of the VMHvl and the phase within the reproductive cycle. Prominent among this, the resting membrane potential of anterior PR+ neurons decreased during the receptive phase, while the excitability of medial PR+ neurons increased during the non-receptive phase. During the receptive phase of the cycle, posterior PR+ neurons simultaneously showed an increase in dendritic complexity and a decrease in spine density. These findings reveal an extensive diversity of local rules driving structural and physiological changes in response to fluctuating levels of sex hormones, supporting the anatomic and functional subdivision of the VMHvl and its possible role in the orchestration of different aspects of female socio-sexual behavior.
Structural basis for the association of PLEKHA7 with membrane-embedded phosphatidylinositol lipids

PLEKHA7 (pleckstrin homology domain containing family A member 7) plays key roles in intracellular signaling, cytoskeletal organization and cell adhesion, and is associated with multiple human cancers. The interactions of its pleckstrin homology (PH) domain with membrane phosphatidyl-inositol-phosphate (PIP) lipids, are critical for proper cellular localization and function, and their inhibition is an attractive target for anti-cancer therapy. While structural data can provide insights in this area, little is known about the way in which PLEKHA7 and other PH domains interact with membrane-embedded PIPs. Here we report atomic-resolution structures of the PLEHA7 PH domain and describe the molecular mechanism for its recognition of membrane-bound PIPs. Using X-ray crystallography, nuclear magnetic resonance (NMR), molecular dynamics (MD) simulations, and isothermal titration calorimetry (ITC), we show – in atomic-level detail – that the interaction of PLEKHA7 with PIPs is multivalent and induces PIP clustering. The PIP binding mechanism is distinct from a discrete one-to-one interaction. Our findings reveal a central role of the membrane assembly in mediating protein-PIP association and provide a roadmap for the design of PLEKHA7-PIP inhibitors.
Effect of portal vein thrombosis on the prognosis of patients with cirrhosis without a liver transplant

Abstract Background: Portal vein thrombosis (PVT) is a relatively common complication of cirrhosis. However, the effect of PVT on the prognosis might not be unequivocal. A systematic review and meta-analysis were performed to investigate the effect of PVT on the prognosis of patients with cirrhosis who have not received a liver transplant. Methods: Three databases, including PubMed, EMBASE, and Cochrane Library, were searched for studies published up to March 2020. The survival or mortality rate of patients with PVT served as the main index to evaluate the prognosis of these patients. Hepatic decompensation served as the index of disease progression. Meta-analyses were conducted using Review Manager software 5.2. Results: Sixteen clinical studies were included and analyzed. PVT was associated with an increased risk of mortality in patients with decompensated cirrhosis. According to the meta-analysis, patients with cirrhosis presenting with PVT had a lower 1-year survival rate than patients without PVT (odds ratio (OR), 0.32; 95% confidence interval (CI), 0.14–0.75; P = . 008). The cumulative survival rates were similar between the 2 groups at 3 years (OR, 1.04; 95% CI, 1.00–1.08; P = .06), 5 years (OR, 1.33; 95% CI, 0.71–2.48; P = .38) and 10 years (OR, 1.24; 95% CI, 0.79–1.93; P = .35). PVT was associated with a higher mortality rate in patients with Child-Pugh class B and C disease. A significantly increased risk of death was observed in patients with complete PVT. Patients with both PVT and cirrhosis had a higher rate of decompensation than patients without PVT. Conclusions: The presence of PVT might exert a slight effect on the overall prognosis of patients with cirrhosis. PVT might mainly affect the short-term prognosis by increasing hepatic decompensation events in patients with cirrhosis. However, PVT might not influence the long-term prognosis of patients with cirrhosis.
Effects of long noncoding RNA on prognosis of oral squamous cell carcinoma

Abstract Background: Long noncoding RNA (lncRNA) is reported to be upregulated in many tumors. Although the expression of lncRNA in oral squamous cell carcinoma has been assessed, the association between lncRNA expression and prognosis or clinicopathological feature still remains controversial. Therefore, we conducted a meta-analysis to verify whether lncRNA expression was related to prognosis or clinicopathological features in patients with oral squamous cell carcinoma. Methods: We searched Embase, PubMed, Web of Science, Cochrane library, Chinese National Knowledge Infrastructure, and Wanfang databases from inception to February 2021. The language included Chinese and English. The published literature on lncRNA expression and prognosis or clinicopathological characteristics of patients with oral squamous cell carcinoma was statistically analyzed. The combination of hazard ratios (HRs), odds ratios (OR), and 95% confidence intervals (95% CIs) were applied to evaluate the effects of lncRNA on the prognosis and clinicopathological features of oral squamous cell carcinoma. Results: This study could provide a comprehensive review of the available evidence of lncRNA on the prognosis and clinicopathological features of oral squamous cell carcinoma. Conclusion: The conclusion of our study will provide the updated evidence to judge the lncRNA on the prognosis and clinicopathological features of oral squamous cell carcinoma.
Local adaptation of Mycobacterium tuberculosis on the Tibetan Plateau

Significance The global distribution of different Mtb lineages is very structured, with a few lineages that are globally widespread, whereas many others are restricted to particular geographic regions. Although local adaptation has been a favored model for explaining the sympatric relationship between the bacteria and host in these geographic regions, this has been difficult to study. Human migration has led to intermixing of ethnicities and has disturbed the bacterial population structure, thereby masking the putative genetic determinants that may have evolved from selection pressures in a given region. Here, by analyzing the genomes of hundreds of Mtb strains sampled from the relatively isolated population of Tibetan, we provide genetic evidence that Mtb can evolve to adapt to local populations and environments. During its global dispersal, Mycobacterium tuberculosis (Mtb) has encountered varied geographic environments and host populations. Although local adaptation seems to be a plausible model for describing long-term host–pathogen interactions, genetic evidence for this model is lacking. Here, we analyzed 576 whole-genome sequences of Mtb strains sampled from different regions of high-altitude Tibet. Our results show that, after sequential introduction of a few ancestral strains, the Tibetan Mtb population diversified locally while maintaining strict separation from the Mtb populations on the lower altitude plain regions of China. The current population structure and estimated past population dynamics suggest that the modern Beijing sublineage strains, which expanded over most of China and other global regions, did not show an expansion advantage in Tibet. The mutations in the Tibetan strains showed a higher proportion of A > G/T > C transitions than strains from the plain regions, and genes encoding DNA repair enzymes showed evidence of positive selection. Moreover, the long-term Tibetan exclusive selection for truncating mutations in the thiol-oxidoreductase encoding sseA gene suggests that Mtb was subjected to local selective pressures associated with oxidative stress. Collectively, the population genomics of Mtb strains in the relatively isolated population of Tibet provides genetic evidence that Mtb has adapted to local environments.
Two mouse lines selected for large litter size display different lifetime fecundities

We recently described two outbred mouse lines that were selected for large litter size at first delivery. However, lifetime fecundity appears to be economically more important for the husbandry of many polytocous species for which mouse lines might serve as bona fide animal models (e.g. for pigs). In the present study, we compared the lifetime fecundities of two highly fertile mouse lines (FL1 and FL2: >20 offspring/litter at first delivery) with those of an unselected control line (ctrl) and two lines that were selected for high body weight (DU6) and high protein mass (DU6P) without selection pressure on fertility. We tested the hypothesis that selection for large litter size at first parturition would also increase lifetime fecundity in mice, and we observed very large differences between lines. Whereas FL1 and ctrl delivered up to nine and ten litters, none of the DU6 and DU6P females gave birth to more than five litters. In line with this observation, FL1 delivered the most pups per lifetime (85.7/female). FL2 females produced the largest average litter sizes (20.4 pups/litter) in the first four litters; however, they displayed a reduced number of litters. With the exception of ctrl, litter sizes declined from litter to litter. Repeated delivery of litters with high offspring numbers did not affect the general health of FL females. The presented data demonstrate that two biodiverse, highly fertile mouse lines selected for large litter size at first delivery show different lifetime reproductive fitness levels. Thus, these mouse lines might serve as valuable mouse models for investigating lifetime productivity and longevity in farm animals.
Subjective experiences of participating in an attachment-based early intervention parenting program

This qualitative study evaluated an attachment-based group parenting program that utilises mentalisation-based approach. The Building Early Attachment and Resilience (BEAR) program was designed to promote parent-child attachment across the perinatal period and has pre- and post-natal arms. The post-natal component targets mothers and infants at risk for early disturbances of attachment to, and emotional interaction. This evaluation study aimed to explore mothers’ subjective experiences of the post-natal BEAR program in encouraging mothers’ reflection on their role as a parent. Thirteen mothers were interviewed. Transcripts were analysed using thematic analysis, with five themes emerging. Overall, mothers reported that the intervention promoted reflection about the parenting role, contributed to perceptions of improved mother-infant interactions and increased understanding of their infant’s internal experiences. The results suggest the BEAR program is acceptable and facilitates the development of secure parent-infant attachment.
California Bullying Victimization Scale-Retrospective (CBVS-R): Validation of the Spanish Adaptation.

BACKGROUND Bullying in childhood and adolescence is a worldwide problem. There is a general lack of validated retrospective measures of bullying, especially in Spanish-speaking populations. The present study aimed to adapt the retrospective version of the California Bullying Victimization Scale (CBVS-R) to Spanish and examine its psychometric properties. METHOD The CBVS-R was translated and adapted into Spanish, and school victimization was evaluated in a sample of 1,855 Spanish adults (69.3% women). Factor structure, test-retest reliability, and predictive validity were explored. The types of victimization by educational level and the total victimization score for each participant were analyzed. RESULTS Factor analysis showed a one-factor structure. Values of internal consistency (α = .80) and test-retest reliability ( r = .87, k = .73) were satisfactory. Victimization was associated with self-reports of mental health. Victimization patterns peaked around adolescence, the most frequent victimizing behavior was being teased or called names. CONCLUSIONS Results support the usefulness and suitability of the Spanish adaptation of the CBVS-R as a retrospective self-report measure of bullying victimization in adults.
Feature screening with large‐scale and high‐dimensional survival data

Data with a huge size present great challenges in modeling, inferences, and computation. In handling big data, much attention has been directed to settings with “large p small n”, and relatively less work has been done to address problems with p and n being both large, though data with such a feature have now become more accessible than before, where p represents the number of variables and n stands for the sample size. The big volume of data does not automatically ensure good quality of inferences because a large number of unimportant variables may be collected in the process of gathering informative variables. To carry out valid statistical analysis, it is imperative to screen out noisy variables that have no predictive value for explaining the outcome variable. In this paper, we develop a screening method for handling large‐sized survival data, where the sample size n is large and the dimension p of covariates is of non‐polynomial order of the sample size n, or the so‐called NP‐dimension. We rigorously establish theoretical results for the proposed method and conduct numerical studies to assess its performance. Our research offers multiple extensions of existing work and enlarges the scope of high‐dimensional data analysis. The proposed method capitalizes on the connections among useful regression settings and offers a computationally efficient screening procedure. Our method can be applied to different situations with large‐scale data including genomic data.
Variation in the seventh lumbar vertebra and the lumbosacral junction morphometry associated with the sacrocaudal fusion in greyhounds

The lumbosacral joint is where the 7th lumbar vertebra (L.7) articulates within the sacrum. It is a clinically important area in the dog because of its relatively large range of motion. The current study aims to determine the possible differences in the length of the L.7 vertebra and the angle of the lumbosacral junction among greyhounds of standard and those of fused sacra, and to determine the potential association of sex, body mass and type of fused sacrum (standard and fused) on the morphology of the L.7 vertebra and the angle of the lumbosacral junction. Radiographs of 55 greyhound cadavers were used for radiographing; all radiographic images were stored and measured using X‐ray acquisition software, and then analysed using descriptive statistics, multiple linear regression and logistic regression. The results of this study showed a significant increase (p < .008) in the length of the L.7 vertebra and the angle of the lumbosacral junction (p < .028) in greyhounds with fused sacra comparing with those of standard sacra, but the L.6 length was not significant (p = .431). Differences have been found in the length of L.7 vertebra and the angle of the lumbosacral junction in greyhounds. It was found that in greyhounds, any variation in the sacrum's anatomical features may alter the structure of the surrounding anatomical structures such as the L.7 vertebra and lumbosacral junction.