Miracle-dz/UniFAR-FTUs huggingface dataset:
Automated Cancer Subtyping via Vector Quantization Mutual Information Maximization

Cancer subtyping is crucial for understanding the nature of tumors and providing suitable therapy. However, existing labelling methods are medically controversial, and have driven the process of subtyping away from teaching signals. Moreover, cancer genetic expression profiles are high-dimensional, scarce, and have complicated dependence, thereby posing a serious challenge to existing subtyping models for outputting sensible clustering. In this study, we propose a novel clustering method for exploiting genetic expression profiles and distinguishing subtypes in an unsupervised manner. The proposed method adaptively learns categorical correspondence from latent representations of expression profiles to the subtypes output by the model. By maximizing the problem -- agnostic mutual information between input expression profiles and output subtypes, our method can automatically decide a suitable number of subtypes. Through experiments, we demonstrate that our proposed method can refine existing controversial labels, and, by further medical analysis, this refinement is proven to have a high correlation with cancer survival rates.
Asymmetric Learned Image Compression with Multi-Scale Residual Block, Importance Map, and Post-Quantization Filtering

Recently, deep learning-based image compression has made signifcant progresses, and has achieved better ratedistortion (R-D) performance than the latest traditional method, H.266/VVC, in both subjective metric and the more challenging objective metric. However, a major problem is that many leading learned schemes cannot maintain a good trade-off between performance and complexity. In this paper, we propose an effcient and effective image coding framework, which achieves similar R-D performance with lower complexity than the state of the art. First, we develop an improved multi-scale residual block (MSRB) that can expand the receptive feld and is easier to obtain global information. It can further capture and reduce the spatial correlation of the latent representations. Second, a more advanced importance map network is introduced to adaptively allocate bits to different regions of the image. Third, we apply a 2D post-quantization flter (PQF) to reduce the quantization error, motivated by the Sample Adaptive Offset (SAO) flter in video coding. Moreover, We fnd that the complexity of encoder and decoder have different effects on image compression performance. Based on this observation, we design an asymmetric paradigm, in which the encoder employs three stages of MSRBs to improve the learning capacity, whereas the decoder only needs one stage of MSRB to yield satisfactory reconstruction, thereby reducing the decoding complexity without sacrifcing performance. Experimental results show that compared to the state-of-the-art method, the encoding and decoding time of the proposed method are about 17 times faster, and the R-D performance is only reduced by less than 1% on both Kodak and Tecnick datasets, which is still better than H.266/VVC(4:4:4) and other recent learning-based methods. Our source code is publicly available at https://github.com/fengyurenpingsheng.
How to Combine Variational Bayesian Networks in Federated Learning

Federated Learning enables multiple data centers to train a central model collaboratively without exposing any confidential data. Even though deterministic models are capable of performing high prediction accuracy, their lack of calibration and capability to quantify uncertainty is problematic for safety-critical applications. Different from deterministic models, probabilistic models such as Bayesian neural networks are relatively well-calibrated and able to quantify uncertainty alongside their competitive prediction accuracy. Both of the approaches appear in the federated learning framework; however, the aggregation scheme of deterministic models cannot be directly applied to probabilistic models since weights correspond to distributions instead of point estimates. In this work, we study the effects of various aggregation schemes for variational Bayesian neural networks. With empirical results on three image classification datasets, we observe that the degree of spread for an aggregated distribution is a significant factor in the learning process. Hence, we present an investigation on the question of how to combine variational Bayesian networks in federated learning, while providing benchmarks for different aggregation settings.
Generic E-Variables for Exact Sequential k-Sample Tests that allow for Optional Stopping

We develop E-variables for testing whether two or more data streams come from the same source or not, and more generally, whether the difference between the sources is larger than some minimal effect size. These E-variables lead to exact, nonasymptotic tests that remain safe, i.e. keep their type-I error guarantees, under flexible sampling scenarios such as optional stopping and continuation. In special cases our E-variables also have an optimal 'growth' property under the alternative. While the construction is generic, we illustrate it through the special case of k x 2 contingency tables, where we also allow for the incorporation of different restrictions on a composite alternative. Comparison to p-value analysis in simulations and a real-world example show that E-variables, through their flexibility, often allow for early stopping of data collection, thereby retaining similar power as classical methods, while also retaining the option of extending or combining data afterwards.
BIOPHYSICAL ASPECTS OF MICROSPHERE ENGULFMENT

A quantitative investigation into the mechanism of neutrophil phagocytosis of opsonized microspheres possessing well defined dimensions was undertaken. Three aspects were documented: membrane conservation, cell adhesion to the spheres, and active cell cytoplasmic projection around the microspheres. The physical act of internalizing a particle by a cell involves a reduction in its plasma membrane area and an increase in its volume. As a consequence, a cell can internalize only a finite number of particles. A store of membrane area exists on cytoplasmic granules and may be recruited during phagocytosis. Previous measurements of neutrophil membrane area and volume served as a basis for estimates of the maximum number of internalized microspheres. A comparison with experimental prediction based on membrane conservation and degranulation agrees within 10% for a range of microsphere diameters, from 0.5 to 8 ,im. This suggests that the limitation for additional particle uptake in the population of engorged neutrophils is the lack of excess plasma membrane area. In a random population of neutrophils, there was a sub-group, -40%, which could no longer phagocytose before depleting their membrane stores. Several aspects of the engulfment process were investigated to elucidate the cause of this phagocytosis deficiency. It could be shown by single cell observation that these cases were associated with a lack of pseudopod projection, although adhesion was still evident between the cell membrane and the microspheres.
Distinct Patterns of Neural Habituation and Generalization in Youth With Autism, With and Without Sensory Over-Responsivity

Objective: Sensory over-responsivity (SOR), an atypical negative reaction to sensory stimuli, is highly prevalent in Autism Spectrum Disorders (ASD). Prior work has related SOR to increased brain response in sensory-limbic regions. This study investigated where these atypical responses fall in three fundamental stages of sensory processing: 1) arousal (i.e. initial response); 2) habituation (i.e. change in response over time); and 3) generalization of response to novel stimuli. Different areas of atypical response would require distinct intervention approaches. Methods: Functional MRI was used to examine these patterns of neural habituation to two sets of similar mildly aversive auditory and tactile stimuli in 42 high-functioning youth with ASD (21 high-SOR; 21 low-SOR) and 27 age-matched TD youth (age 8-17). The relationship between SOR and change in amygdala-prefrontal functional connectivity across the sensory stimulation was also examined. Results: Across repeated sensory stimulation, ASD-high-SOR youth showed reduced ability to maintain habituation in amygdala and relevant sensory cortices, and to maintain inhibition of irrelevant sensory cortices. These results indicate that sensory habituation is a dynamic, timevarying process dependent on sustained regulation across time, which is a particular deficit in ASD-high-SOR youth. However, ASD-low-SOR youth also showed distinct, non-typical neural response patterns including reduced responsiveness to novel but similar stimuli and increases in prefrontal-amygdala regulation across the sensory exposure. Corresponding author and location of work: Shulamite A. Green, Ph.D., University of California, Los Angeles, Ahmanson-Lovelace Brain Mapping Center, Jane and Terry Semel Institute of Neuroscience and Human Behavior, 660 Charles E. Young Drive South, Los Angeles, CA 90095, shulamite@ucla.edu; 310-983-3667. Author Disclosures: Drs. Green, and Hernandez, Katherine Lawrence, Janelle Liu, Dr. Tsang, Jillian Yeargin, Kaitlin Cummings, and Drs. Laugeson, Dapretto and Bookheimer report no biomedical financial interests or potential conflicts of interests. HHS Public Access Author manuscript Am J Psychiatry. Author manuscript; available in PMC 2020 December 01. Published in final edited form as: Am J Psychiatry. 2019 December 01; 176(12): 1010–1020. doi:10.1176/appi.ajp. 2019.18121333. A uhor M anscript
Real-world changes in adolescents’ ADHD symptoms throughout the day and across school and non-school days

Objective: Research on attention-deficit/hyperactivity disorder (ADHD) points to the possibility that contextual factors (e.g., time of day, school vs. home) may be related to symptoms and impairment. This prior research has relied on laboratory-based or retrospective, global approaches which has limited ecological validity. The present study substantively contributes to the extant literature by examining adolescents’ ADHD symptoms in the real world across the day on both school and non-school days to test whether symptoms worsened throughout the day and were higher on school days relative to non-school days. Method: As part of a larger study, 83 adolescents taking stimulant medication for ADHD (Mage = 14.7, 66% identified as boys/men, 78% White) completed a 17-day ecological momentary assessment protocol that included wake-up and bedtime reports and two reports in the afternoon and evening. These assessments asked about ADHD symptoms and stimulant medication usage since the last report. Hypotheses were tested using multilevel modeling. Results: Accounting for demographic covariates and medication usage, ADHD symptoms worsened quadratically, peaking at the afternoon report and subsequently declining, across school days but not non-school days. Mean-level ADHD symptoms were also worse on school days relative to non-school days. Results did not differ across gender. Conclusions: Our study is the first to examine important environmental factors (school, time of day) in real time in relation to level of naturalistically occurring ADHD symptoms. Our findings highlight the importance of advancing treatments to support adolescents with ADHD on school days and in the afternoon.
Testing the effect of ocular aberrations in the perceived transverse chromatic aberration

We have measured the ocular transverse chromatic aberration (TCA) in 11 subjects using 2D-two-color Vernier alignment, for two pupil diameters, in a polychromatic adaptive optics (AO) system. TCA measurements were performed for two pupil diameters: for a small pupil (2-mm), referred to as ‘optical TCA’ (oTCA), and for a large pupil (6-mm), referred to ‘perceived TCA’ (pTCA). Also, the TCA was measured through both natural aberrations (HOAs) and AO-corrected aberrations. Computer simulations of pTCA incorporated longitudinal chromatic aberration (LCA), the patient’s HOAs measured with Hartmann-Shack, and the Stiles-Crawford effect (SCE), measured objectively by laser ray tracing. The oTCA and the simulated pTCA (no aberrations) were shifted nasally 1.20 arcmin and 1.40 arcmin respectively. The experimental pTCA (-0.27 arcmin horizontally and -0.62 vertically) was well predicted (81%) by simulations when both the individual HOAs and SCE were considered. Both HOAs and SCE interact with oTCA, reducing it in magnitude and changing its orientation. The results indicate that estimations of polychromatic image quality should incorporate patient’s specific data of HOAs, LCA, TCA & SCE. © 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement
AJA1900060 152..164

Purpose: Complaints of auditory perceptual deficits, such as tinnitus and difficulty understanding speech in background noise, among individuals with clinically normal audiograms present a perplexing problem for audiologists. One potential explanation for these “hidden” auditory deficits is loss of the synaptic connections between the inner hair cells and their afferent auditory nerve fiber targets, a condition that has been termed cochlear synaptopathy. In animal models, cochlear synaptopathy can occur due to aging or exposure to noise or ototoxic drugs and is associated with reduced auditory brainstem response (ABR) wave I amplitudes. Decreased ABR wave I amplitudes have been demonstrated among young military Veterans and non-Veterans with a history of firearm use, suggesting that humans may also experience noise-induced synaptopathy. However, the downstream consequences of synaptopathy are unclear. Method: To investigate how noise-induced reductions in wave I amplitude impact the central auditory system, the ABR, the middle latency response (MLR), and the late
The iNKT cell response has differential signaling requirements during Ag-dependent and Ag-independent activation

Invariant natural killer T (iNKT) cells are an innate-like population characterized by their recognition of glycolipid antigens and rapid cytokine production upon activation. Unlike conventional T cells, which require TCR ligation, iNKT cells can also be stimulated independently of their TCR. This feature allows iNKT cells to respond even in the absence of glycolipid antigens, for example during viral infections. Although the TCR-dependent and -independent activation of iNKT cells have been relatively well established, the exact contributions of IL-12, IL-18, and tolllike receptors (TLRs) remain unclear for these two activation pathways. To definitively investigate how these components affect the direct and indirect stimulation of iNKT cells, we used mice deficient for either MyD88 or the IL-12Rβ2 in the T cell lineage. Using these tools, we demonstrate that IL-12, IL-18, and TLRs are completely dispensable for the TCR activation pathway, when a strong agonist is used. In contrast, during murine cytomegalovirus (MCMV) infection when the TCR is not engaged, IL-12 signaling is essential and TLR signaling is expendable. Importantly, we discovered an intrinsic requirement for IL-18 signaling by splenic iNKT cells, but not liver iNKT cells, suggesting that there might be diversity even within the NKT1 population.
GSK3 in Alzheimer’s Disease: Mind the Isoforms

Understanding the molecular signaling pathways that go awry in Alzheimer’s disease (AD) would provide insights into developing novel therapies for this devastating neurodegenerative disease. Previous work has established that hyperactive glycogen synthase kinase-3 (GSK3) is linked to both “sporadic” and “genetic” forms of AD, suggesting a crucial role of GSK3 in AD pathogenesis. Therefore, inhibition of GSK3 activity has been intensely investigated as a potential therapeutic intervention for AD. GSK3 exists in two isoforms: GSK3α and GSK3β. Markedly, recent studies indicate specific contributions of each of the α and β isoforms of GSK3 to AD pathogenesis, suggesting a role of both isoforms in the disease. Here I review recent relevant work investigating isoform-specific roles of GSK3 in AD pathophysiology, highlighting the emerging role of GSK3α, which has been largely overlooked in favor of the more extensive studies of GSK3β.
A lower AFC is Associated with Infertility

Study Objective—To determine whether infertile women have lower antral follicle counts (AFC) than age-matched normal women Design—Casecontrol Setting—Academic center Patients—881 infertile women and 771 women from the community Interventions—Antral follicle count and basal hormone measurements Main outcome measure(s)—Median AFCs and FSH levels were compared between the 2 groups within 5 year age strata, using the median test. A subanalysis was performed by identifying women in the control group with a history of attempting conception without success (Subfertile Group) and with a spontaneous conception in less than 12 months resulting in a live birth (Fertile Group). Age-specific AFC percentiles were calculated and compared within strata determined by age at the time of attempted conception Results—AFCs were significantly lower in infertile women than in controls across age groups up to 40 years of age (P<0.001). Average FSH levels were significantly higher in the younger age infertile group vs. the community (P<0.005). AFC percentiles differ significantly between fertile and subfertile women within the community up until 40 years of age (P<0.02) Conclusion—Decreased AFC in infertile women suggests that factors affecting the size of the remaining follicle pool in younger women also affect oocyte quality and the likelihood of conception
T Cell Antigen Receptor V Gene Usage

Crohn's disease represents part of a spectrum of inflammatory bowel diseases characterized by immune regulatory defects and genetic predisposition. T cell antigen receptor V gene usage by T lymphocytes was investigated using four MAbs specific for various V gene products. One MAb (Ti3a), reactive with V,68 gene products, detected increased numbers ofT cells in a subset of Crohn's disease patients as compared with normal controls and ulcerative colitis patients. In family studies there was no apparent inherited predisposition to the use of V,68 genes, and there was no association between a restriction fragment length polymorphism of the VjB8.1 gene and Crohn's disease. The VtB8+ T cells were concentrated in the mesenteric lymph nodes draining the inflammatory lesions and belonged to both the CD4+ and CD8+ T cell subsets. In contrast, lamina propria and intraepithelial T cells were not enriched in V,68+ T cells, suggesting that these cells were participating in the afferent limb of a gut-associated immune response. The expanded V,#8+ T cells in Crohn's disease appear to result from an immune response to an as yet unknown antigen. (J. Clin. Invest. 1990. 85:1770-1776.) inflammatory bowel disease * family study * RFLP * epithelial cells * cross-reactive monoclonal antibodies
Influenza Enhances Susceptibility to Natural Acquisition and Disease from Streptococcus pneumoniae in Ferrets

The role of respiratory viruses in transmission of Streptococcus pneumoniae is poorly understood. Key questions such as which serotypes are most fit for transmission and disease, and whether influenza virus alters these parameters in a serotype specific manner have not been adequately studied. In a novel model of ferret transmission, we demonstrated that prior infection with influenza virus of donors enhanced pneumococcal transmission and disease. Nasal wash bacterial titers, the incidence of mucosal and invasive disease, and the percentage of contacts infected were all increased. Viral infection of contact ferrets increased their susceptibility to acquisition both in terms of percentage infected and distance over which they could acquire infection. These influenza mediated effects on colonization, transmission and disease were pneumococcal strain dependent. Overall, these data argue that human studies of the relationship between respiratory viral infections, acquisition of pneumococci, and development of disease need further study to be better understood.
Original Contribution Estimated Number of Lifetime Ovulatory Years and Its Determinants in Relation to Levels of Circulating Inflammatory Biomarkers

Reproductive events, such as ovulation, trigger an inflammatory cascade. Few studies have examined their long-term influence on inflammatory profiles. We included 3,393 premenopausal and 3,915 postmenopausal women with intact ovaries/uterus from the Nurses’ Health studies (Nurses’ Health Study (1989–1990) and Nurses’ Health Study II (1996–1999)) in an analysis of the association between lifetime ovulatory years (LOY) and levels of inflammatory biomarkers. We estimated LOY as age at menopause (age at blood collection for premenopausal women) minus age at menarche, subtracting years of oral contraceptive (OC) use and 1 year per pregnancy. After adjustment for other inflammation-related factors (e.g., body mass index, exercise, diet), every 5-year increase in LOY was associated with lower C-reactive protein (CRP) levels in both premenopausal (difference = −11.5%, 95% confidence interval: −15.0, −8.0; P < 0.0001) and postmenopausal (difference = −7.2%, 95% confidence interval: −10.0, −4.3; P < 0.0001) women. Older age at menopause (P = 0.007), earlier menarche (P = 0.007), and shorter duration of OC use (P = 0.002) were associated with lower CRP levels in postmenopausal women, whereas duration of OC use was positively associated with CRP levels in premenopausal women (P < 0.0001). LOY was modestly inversely associated with interleukin 6 in postmenopausal women (P = 0.03). Notably, the associations of CRP with LOY were similar in magnitude to associations with exercise and a healthy diet, though weaker than the association with body mass index.Although many reproductive events induce acute inflammation, increased LOY was associated with lower chronic systemic inflammation even after menopause.