Miracle-dz/UniFAR-FTUs huggingface dataset:
Treatment effect modifiers in hospitalised patients with COVID-19 receiving remdesivir and dexamethasone

Abstract Background The combined effectiveness of remdesivir and dexamethasone in subgroups of hospitalised patients with COVID-19 is poorly investigated. Methods In this nationwide retrospective cohort study, we included 3826 patients with COVID-19 hospitalised between February 2020 and April 2021. The primary outcomes were use of invasive mechanical ventilation and 30-day mortality, comparing a cohort treated with remdesivir and dexamethasone with a previous cohort treated without remdesivir and dexamethasone. We used inverse probability of treatment weighting logistic regression to assess associations with progression to invasive mechanical ventilation and 30-day mortality between the two cohorts. The analyses were conducted overall and by subgroups based on patient characteristics. Results Odds ratio for progression to invasive mechanical ventilation and 30-day mortality in individuals treated with remdesivir and dexamethasone compared to treatment with standard of care alone was 0.46 (95% confidence interval, 0.37–0.57) and 0.47 (95% confidence interval, 0.39–0.56), respectively. The reduced risk of mortality was observed in elderly patients, overweight patients and in patients requiring supplemental oxygen at admission, regardless of sex, comorbidities and symptom duration. Conclusions Patients treated with remdesivir and dexamethasone had significantly improved outcomes compared to patients treated with standard of care alone. These effects were observed in most patient subgroups.
A Robust Image Watermarking using Two

In this paper we present a blind low frequency watermarking scheme on gray level images, which is based on DCT transform and spread spectrum communications technique. We compute the DCT of non overlapping 8x8 blocks of the host image, then using the DC coefficients of each block we construct a low-resolution approximation image. We apply block based DCT on this approximation image, then a pseudo random noise sequence is added into its high frequencies. For detection, we extract the approximation image from the watermarked image, then the same pseudo random noise sequence is generated, and its correlation is computed with high frequencies of the watermarked approximation image. In our method, higher robustness is obtained because of embedding the watermark in low frequency. In addition, higher imperceptibility is gained by scattering the watermark's bit in different blocks. We evaluated the robustness of the proposed technique against many common attacks such as JPEG compression, additive Gaussian noise and median filter. Compared with related works, our method proved to be highly resistant in cases of compression and additive noise, while preserving high PSNR for the watermarked images.
Light-dependent signal transduction in the marine diatom Phaeodactylum tricornutum

Significance Photoacclimation in photosynthetic organisms remains poorly understood. Here the diatom Phaeodactylum tricornutum was used to study long-term responses to low and high growth irradiances. Extreme light conditions lead to suboptimal photon absorption in the plastid, which triggers feedback responses that alter the expression of specific nuclear genes. Surprisingly, multiple essential photoacclimation genes that have been identified in land plants and green algae are absent in diatoms. It is therefore likely that these photoautotrophs, which have a complex evolutionary origin, have evolved distinct mechanistic responses to light variations in the marine environment. Our results suggest that the nuclear genes identified in this study play key roles in feedback signaling between the nucleus and the plastid in diatoms leading to photoacclimation
INVESTIGATION OF THE GERBER-SHIU DISCOUNTED PENALTY FUNCTION ON FINITE TIME HORIZON

In this paper, the classical risk model with exponential claim sizes is considered. The explicit expression of the Gerber-Shiu discounted penalty function (x; ; t) and discounted moments m(x; ; t) on finite time horizon is obtained, where > 0 is the force of interest, x - the initial reserve. Also the expression of the Gerber-Shiu discounted penalty function on time interval [t1; t2] is derived. The dependance of discounted penalty function on the main parameters x; ; ; ; is presented in diagrams, where > 0 is the parameter of Poisson process, > 0 is the safety loading coefficient and is the parameter of claim distribution.
Development and validation of a machine learning‐based tool to predict autism among children

Autism is a lifelong condition for which intervention must occur as early as possible to improve social functioning. Thus, there is great interest in improving our ability to diagnose autism as early as possible. We take a novel approach to this challenge by combining machine learning with maternal and infant health administrative data to construct a prediction model capable of predicting autism disorder (defined as ICD10 84.0) in the general population. The sample included all mother–offspring pairs from the Australian state of New South Wales (NSW) between January 2003 and December 2005 (n = 262,650 offspring), linked across three health administrative data sets including the NSW perinatal data collection (PDC); the NSW admitted patient data collection (APDC) and the NSW mental health ambulatory data collection (MHADC). Our most successful model was able to predict autism disorder with an area under the receiver operating curve of 0.73, with the strongest risk factors for diagnoses found to include offspring gender, maternal age at birth, delivery analgesia, maternal prenatal tobacco disorders, and low 5‐min APGAR score. Our findings indicate that the combination of machine learning and routinely collected admin data, with further refinement and increased accuracy than achieved by us, may play a role in the early detection of autism disorders.
Anisometric Cell/Dysplastic Lipomas in a Retinoblastoma Survivor: Report of a Case with Review of the Literature

Different authors have recently described a subtype of lipoma characterized by variation of adipocyte size, single cell fat necrosis, and a subset with minimal to mild nuclear atypia, and termed these as anisometric cell/dysplastic lipoma (AC/DL). These lipomas follow a benign course and rarely recur. In 3 examples, AC/DL has occurred in patients with childhood retinoblastoma (RB). We report another such example where multiple AC/DL occurred in the neck and back of a 30-year-old male who had germline RB1 gene deletion and bilateral RB in infancy. On excision, all tumors histologically showed similar morphology of adipocyte anisometry, focal single cell necrosis with surrounding binucleated or multinucleated histiocytes, hyperchromatic and minimally atypical lipocyte nuclei, vacuolated Lockhern change, rare foci of fibromyxoid change, occasional mononuclear cell clusters around capillaries, and loss of RB1 immunostaining. Unequivocal atypical cells, lipoblasts, floret-nucleated or multinucleated giant cells were absent. Molecular analysis of tumor cells showed monoallelic RB1 gene loss without amplification of MDM2 and CDK4 genes. Short-term follow up did not show tumor recurrence. AC/DLs in RB survivors are characterized by multiplicity, unifying histology, and benign course. Their biology appears distinct from ordinary lipomas, spindle cell lipomas, and atypical lipomatous tumors.
A Fully Bayesian Bayesian Approach to Logistic Regression

Binary logistic regression is often used in clinical applications to predict the occurrence of medical conditions that arise within a patient population. Point estimations are often made to approximate the unknown regression weights. In doing so, information about the underlying posterior distribution of the weights is lost. We propose a method that views the logistic regression model from a Bayesian perspective and takes into consideration the full posterior of the un- known regression coefficients when computing the probability of belonging to the positive class. This method will be referred to as the Fully Bayesian method. The Fully Bayesian method allows us to quantify the uncertainty in our probability calculations. The work in this paper builds on Kim and Ma’s previous work in which they demonstrated efficiently solvable fully Bayesian estimation techniques. By solving a (convex) Kullback-Leibler divergence problem they were able to obtain a mapping from any log-concave prior to its corresponding posterior distribution thus enabling one to draw independent samples from the posterior with ease. Hav- ing the full posterior is useful in revealing how credible a prediction is and can be utilized to define an abstain strategy. The data set was created from a subsample of de-identified patient data from Kaiser Permanente and consists of a highly im- balanced number of patients that have and have not been diagnosed with asthma. The results show that the overall performance of a Fully Bayesian scheme produces a higher measure of accuracy than the point estimate method.
Interlaminar stress analysis for carbon/epoxy composite space rotors

This paper extends the previous works that appears in the International Journal of Multiphysics, Varatharajoo, Salit and Goh (2010). An approach incorporating cohesive zone modelling technique is incorporated into an optimized flywheel to properly simulate the stresses at the layer interfaces. Investigation on several fiber stacking sequences are also conducted to demonstrate the effect of fiber orientations on the overall rotor stress as well as the interface stress behaviour. The results demonstrated that the rotor interlaminar stresses are within the rotor materials' ultimate strength and that the fiber direction with a combination of 45°/-45°/0° offers the best triple layer rotor among the few combinations selected for this analysis. It was shown that the present approach can facilitate also further investigation on the interface stress behaviour of rotating rotors.
Induction of a single dose of streptozotocin (50 mg) in rat model causes insulin resistance with type 2 diabetes mellitus

Streptozotocin (STZ) is a broad‐spectrum antibiotic that is toxic to the insulin‐producing beta cells of the pancreatic islets. STZ is currently used clinically for the treatment of metastatic islet cell carcinoma of the pancreas and the induction of diabetes mellitus (DM) in rodents. So far, there has been no previous research to show that STZ injection in rodents causes insulin resistance in type 2 diabetes mellitus (T2DM). The purpose of this study was to determine if rats (Sprague–Dawley) developed type 2 diabetes mellitus (insulin resistance) after 72 h of intraperitoneal administration of 50 mg/kg STZ. Rats with fasting blood glucose levels above 11.0 mM, 72 h post‐STZ induction, were used. The body weight and plasma glucose levels were measured every week throughout the 60‐day treatment period. The plasma, liver, kidney, pancreas, and smooth muscle cells were harvested for antioxidant, biochemical analysis, histology, and gene expression studies. The results revealed that STZ was able to destroy the pancreatic insulin‐producing beta cell, as evidenced by an increase in plasma glucose level, insulin resistance, and oxidative stress. Biochemical investigation indicates that STZ can generate diabetes complications through hepatocellular damage, elevated HbA1c, kidney damage, hyperlipidemia, cardiovascular damage, and impairment of the insulin‐signaling pathway.
Discovery of New D‐Ring Modified Isosteviol Derivatives as Potent Cardioprotective Agents against Oxidative Stress‐Trigged Damage

Cardiovascular diseases (CVDs) are a major global health concern, and oxidative stress is known to play a central role in their pathogenesis. The identification of new agents capable of inhibiting oxidative stress presents a promising strategy for preventing and treating CVDs. Natural products and their derivatives offer a valuable source for drug discovery, and isosteviol, a readily available natural product, is known to exhibit cardioprotective effects. In this study, 22 new D‐ring modified isosteviol derivatives were synthesized and evaluated for their cardioprotective effect in vivo using the zebrafish cardiomyopathy model. The findings revealed that derivative 4e exhibited the most potent cardioprotective effect, surpassing its parent compound isosteviol and the positive drug levosimendan. At 1 μM, derivative 4e significantly protected the cardiomyocytes from injury, while at 10 μM it effectively maintained normal heart phenotypes, preventing cardiac dysfunction in zebrafish. Further investigation demonstrated that 4e protected cardiomyocytes from oxidative stress‐induced damage by inhibiting reactive oxygen species overaccumulation, activating superoxide dismutase 2 expression, and enhancing the endogenous antioxidant defense system. These results suggest that isosteviol derivatives, particularly 4e, have the potential to serve as a novel class of cardioprotective agents for the prevention and treatment of CVDs.
β‐Cyclodextrin and folic acid host–guest interaction binding parameters determined by Taylor dispersion analysis and affinity capillary electrophoresis

The thermodynamic properties of molecular recognition in host–guest inclusion complexes can be studied by Taylor dispersion analysis (TDA). Host–guest inclusion complexes have modest size, and it is possible to get convergent results fast, achieving greater certainty for the obtained thermodynamic properties. Cyclodextrins (CDs) and their derivatives can be used as drug carriers that can boost stability, solubility, and bioavailability of physiologically active substances. A simple and effective approach for assessing the binding properties of CD complexes that are critical in the early stages of drug and formulation development is needed to fully understand the process of CD and guest molecules’ complex formation. In this work, TDA was successfully used to rapidly determine interaction parameters, including binding constant and stoichiometry, between β‐CD and folic acid (FA) along with the diffusivities of the free FA and its complex with β‐CD. Additionally, the FA diffusion coefficient obtained by TDA was compared to the results previously obtained by nuclear magnetic resonance. Affinity capillary electrophoresis (ACE) was also used to compare the binding constants obtained by different methods. The results showed that the binding constants obtained by ACE were somewhat lower than those obtained by the two TDA procedures.
Assessment of genotoxicity induced by subchronic exposure to graphene in HaCaT human skin cell line

Abstract The applications of graphene-based materials (GBMs) and their processing involve prolonged contact with cellular barriers such as human skin. Even though the potential cytotoxicity of graphene has been studied in recent years, the impact of long-term graphene exposure has rarely been explored. We tested in the HaCaT epithelial cells, in vitro, the effect of subchronic treatments with sublethal doses of four different, well-characterized GBMs, two commercial graphene oxides (GO) and two few-layer graphenes (FLG). Cells were exposed weekly to low doses of the GBMs for 14 days, 30 days, 3 months, and 6 months. GBMs-cells uptake was assessed by confocal microscopy. Cell death and cell cycle were determined by fluorescence microscopy and cytometry. DNA damage was measured by comet assay and γ-H2AX staining, followed by the determination of p-p53 and p-ATR by immunolabeling. Subchronic exposure to different GBMs at noncytotoxic doses has potential genotoxic effects on HaCaT epithelial cells that can be recovered depending on the GBM and exposure time. Specifically, GO-induced genotoxicity can be detected after 14 and 30 days from treatment. At this time, FLG appears less genotoxic than GO, and cells can recover more quickly when genotoxic pressure disappears after some days of removal of the GBM. Long-term exposure, 3 and 6 months, to different GBMs induces permanent, nonreversible, genotoxic damage comparable to the exerted by arsenite. This should be considered for the production and future applications of GBMs in scenarios where low concentrations of the material interact chronically with epithelial barriers.
Postoperative adjuvant transarterial chemoembolisation improves survival of hepatocellular carcinoma patients with microvascular invasion: A multicenter retrospective cohort

Abstract Background We aimed to investigate the efficacy of postoperative adjuvant transarterial chemoembolisation (PA‐TACE) in patients with hepatocellular carcinoma (HCC) complicated by microvascular invasion (MVI). Methods A retrospective analysis of 1505 patients with HCC who underwent hepatectomy at four medical centers, including 782 patients who received PA‐TACE and 723 patients who did not receive adjuvant PA‐TACE, has been conducted. Propensity score matching (PSM) (1:1) was performed on the data to minimise selection bias, which resulted in a balanced clinical profile between groups. Results After PSM, 620 patients who received PA‐TACE and 620 patients who did not receive PA‐TACE were included. Disease‐free survival (DFS, 1‐, 2‐, and 3‐year: 88%‐68%‐61% vs. 70%‐58%‐51%, p < 0.001) and overall survival (OS, 1‐, 2‐, and 3‐year: 96%‐89%‐82% vs. 89%‐77%‐67%, p < 0.001) were significantly higher in patients who received PA‐TACE than in those who did not. Patients with MVI who received PA‐TACE had significantly higher DFS (1‐, 2‐, and 3‐year: 68%‐57%‐48% vs. 46%‐31%‐27%, p < 0.001) and OS (1‐, 2‐, and 3‐year: 96%‐84%‐77% vs. 79%‐58%‐40%, p < 0.001) than those who did not receive PA‐TACE. Among the six different liver cancer stages, MVI‐negative patients did not have significant survival outcomes from PA‐TACE (p > 0.05), whereas MVI‐positive patients achieved higher DFS and OS from it (p < 0.05). Liver dysfunction, fever, and nausea/vomiting were the most common adverse events in patients receiving PA‐TACE. There was no significant difference in grade 3 or 4 adverse events between the groups (p > 0.05). Conclusions Postoperative adjuvant transarterial chemoembolisation has a good safety profile and may be a potentially beneficial treatment modality for survival outcomes in patients with HCC, especially those with concomitant MVI.
Impaired AMPARs Translocation into Dendritic Spines with Motor Skill Learning in the Fragile X Mouse Model

Abstract Motor skill learning induces changes in synaptic structure and function in the primary motor cortex (M1). In the fragile X syndrome (FXS) mouse model an impairment in motor skill learning and associated formation of new dendritic spines was previously reported. However, whether modulation of synaptic strength through trafficking of AMPA receptors (AMPARs) with motor skill training is impaired in FXS is not known. Here, we performed in vivo imaging of a tagged AMPA receptor subunit, GluA2, in layer (L)2/3 neurons in the primary motor cortex of wild-type (WT) and Fmr1 knock-out (KO) male mice at different stages of learning a single forelimb-reaching task. Surprisingly, in the Fmr1 KO mice, despite impairments in learning there was no deficit in motor skill training-induced spine formation. However, the gradual accumulation of GluA2 in WT stable spines, which persists after training is completed and past the phase of spine number normalization, is absent in the Fmr1 KO mouse. These results demonstrate that motor skill learning not only reorganizes circuits through formation of new synapses, but also strengthens existing synapses through accumulation of AMPA receptors and GluA2 changes are better associated with learning than new spine formation.
Words or numbers, Mamdani or Sugeno fuzzy systems: a comparative study

In Sugeno’s rules, conclusions are usually considered as being crisp numerical values. On the other hand, in Mamdani’s rules, conclusions are viewed as fuzzy numbers or more rarely as words. This paper makes an attempt at smoothing out this distinction by proposing to handle fuzzy rules with conclusions of the three different types using Mamdani’s reasoning as well as Sugeno’s interpolation mechanism. The extension of Sugeno’s fuzzy systems is carried out using fuzzy arithmetic operators for implementing the weighted mean of fuzzy numbers or words. Concerning Mamdani’s systems, the compositional rule of inference is applied indifferently at the numerical and linguistic levels. After the presentation of the different possible implementations of a rulebased system, the developed ideas are illustrated using a fuzzy rulebase that approximates the arithmetic mean of two quantities.
Atomic-scale interpretation of the quantum oscillations in cuprate superconductors

Cuprate superconductors display unusual features in both k space and real space as the superconductivity is suppressed—a broken Fermi surface, charge density wave, and pseudogap. Contrarily, recent transport measurements on cuprates under high magnetic fields report quantum oscillations (QOs), which imply rather a usual Fermi liquid behavior. To settle the disagreement, we investigated Bi2Sr2CaCu2O8+δ under a magnetic field in an atomic scale. A particle-hole (p–h) asymmetrically dispersing density of states (DOSs) modulation was found at the vortices on a slightly underdoped sample, while on a highly underdoped sample, no trace of the vortex was found even at 13 T. However, a similar p–h asymmetric DOS modulation persisted in almost an entire field of view. From this observation, we infer an alternative explanation of the QO results by providing a unifying picture where the aforementioned seemingly conflicting evidence from angle-resolved photoemission spectroscopy, spectroscopic imaging scanning tunneling microscopy, and magneto-transport measurements can be understood solely in terms of the DOS modulations.
Using conditional independence tests to elucidate causal links in cell cycle regulation in Escherichia coli

Significance Cells across all domains of life grow and divide such that their sizes are tightly regulated, yet the coordination of these processes remains poorly understood. Previous works proposed different models for this coupling in bacteria, in some of which division is controlled by DNA replication processes while in others it is uncoupled from them. We combine experimental data on single-cell E. coli growth with the powerful methodology of causal inference to show that constriction is a cell cycle checkpoint controlled exclusively by DNA replication processes in slow-growth conditions, while additional cues are at play in faster-growth conditions. We also show that control of the DNA replication cycles is more complex than previously thought, paving the way for future studies.
Distinctive alterations in the mesocorticolimbic circuits in various psychiatric disorders

Increasing evidence suggests that psychiatric disorders are linked to alterations in the mesocorticolimbic dopamine‐related circuits. However, the common and disease‐specific alterations remain to be examined in schizophrenia (SCZ), major depressive disorder (MDD), and autism spectrum disorder (ASD). Thus, this study aimed to examine common and disease‐specific features related to mesocorticolimbic circuits.