Miracle-dz/UniFAR-FTUs huggingface dataset:
ReLeQ: An Automatic Reinforcement Learning Approach for Deep Quantization of Neural Networks

Despite numerous state-of-the-art applications of Deep Neural Networks (DNNs) in a wide range of real-world tasks, two major challenges hinder further advances in DNNs: hyperparameter optimization and constrained power resources, which is a significant concern in embedded devices. DNNs become increasingly difficult to train and deploy as they grow in size due to both computational intensity and the large memory footprint. Recent efforts show that quantizing weights of deep neural networks to lower bitwidths takes a significant step toward mitigating the mentioned issues, by reducing memory bandwidth and using limited computational resources which is important for deploying DNN models to devices with limited resources. This paper builds upon the algorithmic insight that the bitwidth of operations in DNNs can be reduced without compromising their classification accuracy. Deep quantization (quantizing bitwidths below eight) while maintaining accuracy, requires magnificent manual effort and hyper-parameter tuning as well as re-training. This paper tackles the aforementioned problems by designing an end to end framework, dubbed ReLeQ, to automate DNN quantization. We formulate DNN quantization as an optimization problem and use a state-of-the-art policy gradient based Reinforcement Learning (RL) algorithm, Proximal Policy Optimization (PPO) to efficiently explore the large design space of DNN quantization and solve the defined optimization problem. To show the effectiveness of ReLeQ, we evaluated it across several neural networks including MNIST, CIFAR10, SVHN. ReLeQ quantizes the weights of these networks to average bitwidths of 2.25, 5 and 4 respectively while maintaining the final accuracy loss below 0.3% .
Thioesterase superfamily member 2 promotes hepatic insulin resistance in the setting of glycerol-3-phosphate acyltransferase 1–induced steatosis

Hepatic insulin resistance in the setting of steatosis is attributable at least in part to the accumulation of bioactive lipids that suppress insulin signaling. The mitochondria-associated glycerol-3-phosphate acyltransferase 1 (GPAT1) catalyzes the first committed step in glycerolipid synthesis, and its activity diverts fatty acids from mitochondrial β-oxidation. GPAT1 overexpression in mouse liver leads to hepatic steatosis even in the absence of overnutrition. The mice develop insulin resistance owing to the generation of saturated diacylglycerol and phosphatidic acid molecular species that reduce insulin signaling by activating PKCϵ and by suppressing mTORC2, respectively. Them2, a mitochondria-associated acyl-CoA thioesterase, also participates in the trafficking of fatty acids into oxidative versus glycerolipid biosynthetic pathways. Them2−/− mice are protected against diet-induced hepatic steatosis and insulin resistance. To determine whether Them2 contributes to hepatic insulin resistance due to hepatic overexpression of GPAT1, recombinant adenovirus was used to overexpress GPAT1 in livers of chow-fed Them2+/+ and Them2−/− mice. Hepatic GPAT1 overexpression led to steatosis in both genotypes. In the setting of GPAT1 overexpression, glucose tolerance was reduced in Them2+/+ but not Them2−/− mice, without influencing whole-body insulin sensitivity or basal hepatic glucose production. Improved glucose tolerance in Them2−/− mice was associated with reduced PKCϵ translocation. Preserved insulin receptor activity was supported by Thr-308 phosphorylation of Akt following GPAT1 overexpression in Them2−/− hepatocytes. These findings suggest a pathogenic role of Them2 in the biosynthesis of glycerolipid metabolites that promote hepatic insulin resistance.
[Relationship between HLA Gene Polymorphism and Aplastic Anemia in Northern Chinese Han Patients].

OBJECTIVE To explore the relationship between HLA-A, -B, -C, -DRB1, -DQB1 gene polymorphism and aplastic anemia （AA）of 65 cases in Northern China. METHODS The high resolution genotyping of HLA-A, -B, -C, -DRB1, -DQB1 alleles in 65 AA patients and 772 healthy controls was performed with polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO), the relationship between HLA-A, -B, -C, -DRB1, -DQB1 gene polymorphism and aplastic anemia was analyzed by Pearson Chi-square，Continuity Correction， Two-sided Fisher's Exact Test and Odds Ratio. RESULTS The HLA-B*1302（10% vs 4.21%）, B*3501（7.69% vs 3.89%）, DRB1* 0701（10% vs 4.73%）, DRB1*0901（19.23% vs 7.58%）, DQB1*0202（9.23% vs 3.76%） gene frequency in AA patients was higher than those in health controls, the difference was statistically significant (P<0.05), the χ2 were 9.049, 4.336, 6.838, 20.974 and 8.968, OR ratio was 2.528, 2.061, 2.239, 2.904 and 2.605. However, the HLA-A*3303（1.54% vs 6.93%）, DQB1*0302（1.54% vs 6.02%） gene frequency in AA patients was lower than those in healthy controls, the difference was statistically significant (P<0.05), the χ2 was 5.726 and 4.505, the OR ratio were 0.210 and 0.244. CONCLUSION The polymorphism of HLA-A, -B, -DRB1, -DQB1 alleles is associate with AA in these patient cases, the HLA-B*1302, HLA-B*3501, HLA-DRB1*0701, HLA-DRB1*0901 and HLA-DQB1*0202 may be sensitive genes to AA, while the HLA-A*3303 and HLA-DQB1*0302 may be protective genes on AA.
Differential association of two PTPN22 coding variants with Crohn's disease and ulcerative colitis

Background: The PTPN22 gene is an important risk factor for human autoimmunity. The aim of this study was to evaluate for the first time the role of the R263Q PTPN22 polymorphism in ulcerative colitis (UC) and Crohn's disease (CD), and to reevaluate the association of the R620W PTPN22 polymorphism with both diseases. Methods: A total of 1677 UC patients, 1903 CD patients, and 3111 healthy controls from an initial case–control set of Spanish Caucasian ancestry and two independent sample sets of European ancestry (Dutch and New Zealand) were included in the study. Genotyping was performed using TaqMan SNP assays for the R263Q (rs33996649) and R620W (rs2476601) PTPN22 polymorphisms. Meta‐analysis was performed on 6977 CD patients, 5695 UC patients, and 9254 controls to test the overall effect of the minor allele of R620W and R263Q polymorphisms. Results: The PTPN22 263Q loss‐of‐function variant showed initial evidence of association with UC in the Spanish cohort (P = 0.026, odds ratio [OR] = 0.61, 95% confidence interval [CI]: 0.39–0.95), which was confirmed in the meta‐analysis (P = 0.013 pooled, OR = 0.69, 95% CI: 0.51–0.93). In contrast, the 263Q allele showed no association with CD (P = 0.22 pooled, OR = 1.16, 95% CI: 0.91–1.47). We found in the pooled analysis that the PTPN22 620W gain‐of‐function variant was associated with reduced risk of CD (P = 7.4E‐06 pooled OR = 0.81, 95% CI: 0.75–0.89) but not of UC (P = 0.88 pooled, OR = 0.98, 95% CI: 0.85–1.15). Conclusions: Our data suggest that two autoimmunity‐associated polymorphisms of the PTPN22 gene are differentially associated with CD and UC. The R263Q polymorphism only associated with UC, whereas the R620W was significantly associated with only CD. (Inflamm Bowel Dis 2011;)
Correction to "Effects of Innovative WALKBOT Robotic-Assisted Locomotor Training on Balance and Gait Recovery in Hemiparetic Stroke: A Prospective, Randomized, Experimenter Blinded Case Control Study With a Four-Week Follow-Up".

The present clinical investigation was to ascertain whether the effects of WALKBOT-assisted locomotor training (WLT) on balance, gait, and motor recovery were superior or similar to the conventional locomotor training (CLT) in patients with hemiparetic stroke. Thirty individuals with hemiparetic stroke were randomly assigned to either WLT or CLT. WLT emphasized on a progressive, conventional locomotor retraining practice (40 min) combined with the WALKBOT-assisted, haptic guidance and random variable locomotor training (40 min) whereas CLT involved conventional physical therapy alone (80 min). Both intervention dosages were standardized and provided for 80 min, five days/week for four weeks. Clinical outcomes included function ambulation category (FAC), Berg balance scale (BBS), Korean modified Barthel index (K-MBI), modified Ashworth scale (MAS), and EuroQol-5 dimension (EQ-5D) before and after the four-week program as well as at follow-up four weeks after the intervention. Two-way repeated measure ANOVA showed significant interaction effect (time $\times$ group) for FAC $(p=0.02)$ , BBS $(p=0.03)$ , and K-MBI $(p=0.00)$ across the pre-training, post-training, and follow-up tests, indicating that WLT was more beneficial for balance, gait and daily activity function than CLT alone. However, no significant difference in other variables was observed. This is the first clinical trial that highlights the superior, augmented effects of the WALKBOT-assisted locomotor training on balance, gait and motor recovery when compared to the conventional locomotor training alone in patients with hemiparetic stroke.
Effect of Combined Epigenetic Treatments and Ectopic NIS Expression on Undifferentiated Thyroid Cancer Cells

Background: Poorly differentiated (PDTC) and anaplastic thyroid (ATC) cancer cells are characterized by the acquisition of epigenetic abnormalities, leading to the silencing of both the sodium iodide co-transporter and the Coxsackie adenovirus receptor. As aberrant histone acetylation and DNA methylation represent epigenetic mechanisms involved in neoplastic transformation, our study investigated the anticancer properties of epigenetic modifiers in thyroid carcinoma. Materials and Methods: The cytotoxicity and gene expression modulation of histone deacetylase and DNA methyltransferase inhibitors were evaluated in both PDTC and ATC. Results: Epigenetic treatments were cytotoxic to tumor thyrocytes and restored sodium iodide co-transporter and Coxsackie adenovirus receptor, expression as well as radioiodine uptake, in PDTC but not in ATC. However, ectopic expression sodium iodide co-transporter re-activated radioiodine incorporation in ATC. Conclusion: The ability of epigenetic treatments to interfere with tumor proliferation and induce Coxsackie adenovirus receptor expression, coupled with the ability of ectopic sodium iodide co-transporter to restore radioiodine uptake, raise the possibility that these therapeutic approaches may provide clinical benefit to patients with thyroid carcinoma refractory to radioiodine treatment.
Nicotinamide Impairs Entry into and Exit from Meiosis I in Mouse Oocytes

Following exit from meiosis I, mammalian oocytes immediately enter meiosis II without an intervening interphase, accompanied by rapid reassembly of a bipolar spindle that maintains condensed chromosomes in a metaphase configuration (metaphase II arrest). Here we study the effect of nicotinamide (NAM), a non-competitive pan-sirtuin inhibitor, during meiotic maturation in mouse oocytes. Sirtuins are a family of seven NAD+-dependent deacetylases (Sirt1-7), which are involved in multiple cellular processes and are emerging as important regulators in oocytes and embryos. We found that NAM significantly delayed entry into meiosis I associated with delayed accumulation of the Cdk1 co-activator, cyclin B1. GVBD was also inhibited by the Sirt2-specific inhibitor, AGK2, and in a very similar pattern to NAM, supporting the notion that as in somatic cells, NAM inhibits sirtuins in oocytes. NAM did not affect subsequent spindle assembly, chromosome alignment or the timing of first polar body extrusion (PBE). Unexpectedly, however, in the majority of oocytes with a polar body, chromatin was decondensed and a nuclear structure was present. An identical phenotype was observed when flavopiridol was used to induce Cdk1 inactivation during late meiosis I prior to PBE, but not if Cdk1 was inactivated after PBE when metaphase II arrest was already established, altogether indicating that NAM impaired establishment rather than maintenance of metaphase II arrest. During meiosis I exit in NAM-treated medium, we found that cyclin B1 levels were lower and inhibitory Cdk1 phosphorylation was increased compared with controls. Although activation of the anaphase-promoting complex-Cdc20 (APC-Cdc20) occurred on-time in NAM-treated oocytes, Cdc20 levels were higher in very late meiosis I, pointing to exaggerated APC-Cdc20-mediated proteolysis as a reason for lower cyclin B1 levels. Collectively, therefore, our data indicate that by disrupting Cdk1 regulation, NAM impairs entry into meiosis I and the establishment of metaphase II arrest.
Robust Short-Lag Spatial Coherence Imaging of Breast Ultrasound Data: Initial Clinical Results

Ultrasound is frequently used in conjunction with mammography in order to detect breast cancer as early as possible. However, due largely to the heterogeneity of breast tissue, ultrasound images are plagued with clutter that obstructs important diagnostic features. Short-lag spatial coherence (SLSC) imaging has proven to be effective at clutter reduction in noisy ultrasound images. <inline-formula> <tex-math notation="LaTeX">$M$ </tex-math></inline-formula>-Weighted SLSC and Robust-SLSC (R-SLSC) imaging were recently introduced to further improve image quality at higher lag values, while R-SLSC imaging has the added benefit of enabling the adjustment of tissue texture to produce a tissue signal-to-noise ratio (SNR) that is quantitatively similar to B-mode speckle SNR. This paper investigates the initial application of SLSC, <inline-formula> <tex-math notation="LaTeX">$M$ </tex-math></inline-formula>-Weighted SLSC, and R-SLSC imaging to nine targets in the female breast [two simple cysts, one complicated cyst, two fibroadenomas, one hematoma, one complex cystic and solid mass, one invasive ductal carcinoma (IDC), and one ductal carcinoma <italic>in situ</italic> (DCIS)]. As expected, R-SLSC beamforming improves cyst and hematoma contrast by up to 6.35 and 1.55 dB, respectively, when compared to the original B-mode image, and similar improvements are achieved with SLSC and <inline-formula> <tex-math notation="LaTeX">$M$ </tex-math></inline-formula>-Weighted SLSC imaging. However, an interesting finding from this initial investigation is that the solid masses (i.e., fibroadenoma, complex cystic and solid mass, IDC, and DCIS), which appear as hypoechoic in the B-mode image, have similarly high coherence to that of surrounding tissue in coherence-based images. This work holds promise for using SLSC, <inline-formula> <tex-math notation="LaTeX">$M$ </tex-math></inline-formula>-Weighted SLSC, and/or R-SLSC imaging to distinguish between fluid-filled and solid hypoechoic breast masses.
2'-Hydroxyflavanone activity in vitro and in vivo against wild-type and antimony-resistant Leishmania amazonensis

Background To overcome the current problems in leishmaniasis chemotherapy, natural products have become an interesting alternative over the past few decades. Flavonoids have been studied as promising family of compounds for leishmaniasis treatment. 2’-Hydroxyflavanone (2HF) is a flavanone, a class of flavonoid that has shown promising results in cancer studies. In this study, we demonstrated the effects of 2HF in vitro and in vivo against wild-type and antimony-resistant Leishmania amazonensis promastigotes. Methodology/Principal findings 2HF was effective against promastigotes and the intracellular amastigote form, decreasing the infection index in macrophages infected with wild-type and antimony-resistant promastigotes, but it was not toxic to macrophages. In silico analysis indicated 2HF as a good oral candidate for leishmaniasis treatment. In vivo, 2HF was able to reduce the lesion size and parasite load in a murine model of cutaneous leishmaniasis using wild-type and antimony-resistant promastigotes, demonstrating no cross-resistance with antimonials. Conclusions/Significance Taken together, these results suggest 2HF as a potential candidate for leishmaniasis chemotherapy for cutaneous leishmaniasis caused by both wild-type and antimony-resistant Leishmania species by oral administration. Furthermore, studies should be conducted to determine the ideal dose and therapeutic regimen.
Characterising risk of in-hospital mortality following cardiac arrest using machine learning: A retrospective international registry study

Background Resuscitated cardiac arrest is associated with high mortality; however, the ability to estimate risk of adverse outcomes using existing illness severity scores is limited. Using in-hospital data available within the first 24 hours of admission, we aimed to develop more accurate models of risk prediction using both logistic regression (LR) and machine learning (ML) techniques, with a combination of demographic, physiologic, and biochemical information. Methods and findings Patient-level data were extracted from the Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database for patients who had experienced a cardiac arrest within 24 hours prior to admission to an intensive care unit (ICU) during the period January 2006 to December 2016. The primary outcome was in-hospital mortality. The models were trained and tested on a dataset (split 90:10) including age, lowest and highest physiologic variables during the first 24 hours, and key past medical history. LR and 5 ML approaches (gradient boosting machine [GBM], support vector classifier [SVC], random forest [RF], artificial neural network [ANN], and an ensemble) were compared to the APACHE III and Australian and New Zealand Risk of Death (ANZROD) predictions. In all, 39,566 patients from 186 ICUs were analysed. Mean (±SD) age was 61 ± 17 years; 65% were male. Overall in-hospital mortality was 45.5%. Models were evaluated in the test set. The APACHE III and ANZROD scores demonstrated good discrimination (area under the receiver operating characteristic curve [AUROC] = 0.80 [95% CI 0.79–0.82] and 0.81 [95% CI 0.8–0.82], respectively) and modest calibration (Brier score 0.19 for both), which was slightly improved by LR (AUROC = 0.82 [95% CI 0.81–0.83], DeLong test, p < 0.001). Discrimination was significantly improved using ML models (ensemble and GBM AUROCs = 0.87 [95% CI 0.86–0.88], DeLong test, p < 0.001), with an improvement in performance (Brier score reduction of 22%). Explainability models were created to assist in identifying the physiologic features that most contributed to an individual patient’s survival. Key limitations include the absence of pre-hospital data and absence of external validation. Conclusions ML approaches significantly enhance predictive discrimination for mortality following cardiac arrest compared to existing illness severity scores and LR, without the use of pre-hospital data. The discriminative ability of these ML models requires validation in external cohorts to establish generalisability.
CREB/Wnt10b mediates the effect of COX‐2 on promoting BMP9‐induced osteogenic differentiation via reducing adipogenic differentiation in mesenchymal stem cells

Bone morphogenetic protein 9 (BMP9) is one of the most potent osteogenic factors, which may be a potential candidate for bone tissue engineering. However, the osteogenic capacity of BMP9 still need to be further enhanced. In this study, we determined the effect of Wnt10b on BMP9‐induced osteogenic differentiation in mesenchymal stem cell (MSCs) and the possible mechanism underlying this process. We introduced the polymerase chain reaction (PCR), Western blot analysis, histochemical stain, ectopic bone formation, and microcomputed tomography analysis to evaluate the effect of Wnt10b on BMP9‐induced osteogenic differentiation. Meanwhile, PCR, Western blot analysis, chromatin immunoprecipitation, and immunoprecipitation were used to analyze the possible relationship between BMP9 and Wnt10b. We found that BMP9 upregulates Wnt10b in C3H10T1/2 cells. Wnt10b increases the osteogenic markers and bone formation induced by BMP9 in C3H10T1/2 cells, and silencing Wnt10b decreases these effects of BMP9. Meanwhile, Wnt10b enhances the level of phosphorylated Smad1/5/8 (p‐Smad1/5/8) induced by BMP9, which can be reduced by silencing Wnt10b. On the contrary, Wnt10b inhibits adipogenic markers induced by BMP9, which can be decreased by silencing Wnt10b. Further analysis indicated that BMP9 upregulates cyclooxygenase‐2 (COX‐2) and phosphorylation of cAMP‐responsive element binding (p‐CREB) simultaneously. COX‐2 potentiates the effect of BMP9 on increasing p‐CREB and Wnt10b, while silencing COX‐2 decreases these effects. p‐CREB interacts with p‐Smad1/5/8 to bind the promoter of Wnt10b in C3H10T1/2 cells. Our findings suggested that Wnt10b can promote BMP9‐induced osteogenic differentiation in MSCs, which may be mediated through enhancing BMP/Smad signal and reducing adipogenic differentiation; BMP9 may upregulate Wnt10b via the COX‐2/p‐CREB‐dependent manner.
A MURINE VIRUS (JHM) CAUSING DISSEMINATED ENCEPHALOMYELITIS WITH EXTENSIVE DESTRUCTION OF MYELIN

A description has been given of the pathologic changes produced experimentally in animals by the inoculation of a virus material obtained from a mouse with spontaneous encephalomyelitis. The most distinctive feature of the lesions in the central nervous system is the widespread destruction of myelin. Giant cells derived from a variety of tissue elements characterize the early lesions. The liver in the majority of cases is the seat of focal necrosis. In some mice, infected with large doses by the intravenous route, there is produced massive necrosis of the liver, with fat infiltration and calcification. Giant cells are occasionally found in lymphatic tissue, but no significant changes were noted in other organs. Inclusions or elementary bodies were not demonstrated in the lesions. Similar lesions were produced by the inoculation of mouse virus into hamsters. In rats, the lesions were of a more chronic character. The relation of this disease to other demyelinating diseases of man and animals is discussed.
G-CSF does not influence C2C12 myogenesis despite receptor expression in healthy and dystrophic skeletal muscle

Granulocyte-colony stimulating factor (G-CSF) increases recovery of rodent skeletal muscles after injury, and increases muscle function in rodent models of neuromuscular disease. However, the mechanisms by which G-CSF mediates these effects are poorly understood. G-CSF acts by binding to the membrane spanning G-CSFR and activating multiple intracellular signaling pathways. Expression of the G-CSFR within the haematopoietic system is well known, but more recently it has been demonstrated to be expressed in other tissues. However, comprehensive characterization of G-CSFR expression in healthy and diseased skeletal muscle, imperative before implementing G-CSF as a therapeutic agent for skeletal muscle conditions, has been lacking. Here we show that the G-CSFR is expressed in proliferating C2C12 myoblasts, differentiated C2C12 myotubes, human primary skeletal muscle cell cultures and in mouse and human skeletal muscle. In mdx mice, a model of human Duchenne muscular dystrophy (DMD), G-CSF mRNA and protein was down-regulated in limb and diaphragm muscle, but circulating G-CSF ligand levels were elevated. G-CSFR mRNA in the muscles of mdx mice was up-regulated however steady-state levels of the protein were down-regulated. We show that G-CSF does not influence C2C12 myoblast proliferation, differentiation or phosphorylation of Akt, STAT3, and Erk1/2. Media change alone was sufficient to elicit increases in Akt, STAT3, and Erk1/2 phosphorylation in C2C12 muscle cells and suggest previous observations showing a G-CSF increase in phosphoprotein signaling be viewed with caution. These results suggest that the actions of G-CSF may require the interaction with other cytokines and growth factors in vivo, however these data provides preliminary evidence supporting the investigation of G-CSF for the management of muscular dystrophy.