Miracle-dz/UniFAR-FTUs huggingface dataset:
Richter Syndrome: From Molecular Pathogenesis to Druggable Targets

Simple Summary Chronic lymphocytic leukemia represents the most frequent leukemia in adults and evolves from an indolent phase to an aggressive lymphoma in 5–10% of the cases. Such clinico-pathologic transformation is known as Richter syndrome and represents a major unmet medical need because of treatment refractoriness, lack of targeted therapeutic strategies and unsatisfactory survival rates. Molecular investigations by innovative approaches have clarified in detail the pathogenesis of Richter syndrome and have led to the identification of the genetic and biologic changes associated with its evolution from indolent to aggressive disease. Knowledge of the molecular profile of Richter syndrome has revealed several molecular targets that may be exploited for devising novel therapeutic strategies, both with small molecules acting as pathway inhibitors and with monoclonal antibodies, that also include drug immunoconjugates. Clinical trials with these novel medicines are ongoing and may pave the way to a precision medicine approach to Richter syndrome. Abstract Richter syndrome (RS) represents the occurrence of an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL), in patients with chronic lymphocytic leukemia (CLL). Most cases of RS originate from the direct transformation of CLL, whereas 20% are de novo DLBCL arising as secondary malignancies. Multiple molecular mechanisms contribute to RS pathogenesis. B-cell receptor (BCR) overreactivity to multiple autoantigens is due to frequent stereotyped BCR configuration. Genetic lesions of TP53, CDKN2A, NOTCH1 and c-MYC deregulate DNA damage response, tumor suppression, apoptosis, cell cycle and proliferation. Hyperactivation of Akt and NOTCH1 signaling also plays a role. Altered expression of PD-1/PD-L1 and of other immune checkpoints leads to RS resistance to cytotoxicity exerted by T-cells. The molecular features of RS provide vulnerabilities for therapy. Targeting BCR signaling with noncovalent BTK inhibitors shows encouraging results, as does the combination of BCL2 inhibitors with chemoimmunotherapy. The association of immune checkpoint inhibitors with BCL2 inhibitors and anti-CD20 monoclonal antibodies is explored in early phase clinical trials with promising results. The development of patient-derived xenograft mice models reveals new molecular targets for RS, exemplified by ROR1. Although RS still represents an unmet medical need, understanding its biology is opening new avenues for precision medicine therapy.
Optical excitation of electron glasses

Electron-glasses can be readily driven far from equilibrium by a variety of means. Several mechanisms to excite the system and their relative merits are reviewed. In this study we focus on the process of exciting electron-glasses by interaction with near infrared radiation. The efficiency of this protocol varies considerably among different electron-glasses, but it only weakly depends on their resistance at liquid helium temperatures. A dramatic enhancement of the excitation efficiency is observed upon doping crystalline indium-oxide with Au. Some enhancement is observed also in samples doped with Pb but this enhancement fades away with time unlike the situation in the Au-doped samples. Several structural and analytical tools are used to characterize the changes in the materials that may be responsible for these effects. Possible routes by which high-frequency electromagnetic fields take the system far from equilibrium are discussed.
THEORETICAL AND EXPERIMENTAL ASPECTS OF QUANTUM DISCORD AND RELATED MEASURES

Correlations are a very important tool in the study of multipartite systems, for both classical and quantum ones. The discussion about the quantum nature of correlations permeates Physics since Einstein, Podolski and Rosen published their famous article criticizing quantum mechanics. Here, we provide a short review about the quantum nature of correlations, discussing both its theoretical and experimental aspects. We focus on quantum discord and related measures. After discussing their fundamental aspects (theoretically and experimentally), we proceed by analysing the dynamical behavior of correlations under decoherence as well as some applications in different scenarios, such as quantum computation and relativity, passing through critical and biological systems.
Cable Decoupling and Cable-Based Stiffening of Continuum Robots

Cable-driven continuum robots, which are robots with a continuously flexible backbone and no identifiable joints that are actuated by cables, have shown great potential for many applications in unstructured, uncertain environments. However, the standard design for a cable-driven continuum robot segment, which bends a continuous backbone along a circular arc, has many compliant modes of deformation which are uncontrolled, and which may result in buckling or other undesirable behaviors if not ameliorated. In this paper, we detail an approach for using additional cables to selectively stiffen planar cable-driven robots without substantial coupling to the actuating cables. A mechanics-based model based on the planar Cosserat equations is used to find the design conditions under which additional cables can be routed without coupling of the cable lengths for small deformations. Simulations show that even for relatively large deformations, coupling remains small. A prototype is evaluated, and it is demonstrated that the compliance of the robot is substantially modified relative to the same robot without stiffening cables. Additional stiffening cables are shown to increase the end-effector output stiffness by a factor of approximately 10 over a typical design with actuating cables.
Bose-Einstein condensation of 85 Rb by direct evaporation in an optical dipole trap

We report a simple method for the creation of Bose-Einstein condensates of 85Rb by direct evaporation in a crossed optical dipole trap. The independent control of the trap frequencies and magnetic bias field afforded by the trapping scheme permits full control of the trapped atomic sample, enabling the collision parameters to be easily manipulated to achieve efficient evaporation in the vicinity of the 155 G Feshbach resonance. We produce nearly pure condensates of up to 4×104 atoms and demonstrate the tunable nature of the atomic interactions.
Risk of dementia according to the severity of chronic periodontitis in Korea: a nationwide retrospective cohort study

OBJECTIVES We investigated the risk of dementia in older adults with chronic periodontitis according to the severity of periodontitis. METHODS Data on patients with chronic periodontitis were extracted from the National Health Insurance Service-Senior cohort database from 2002 to 2014. Among 52,728 subjects eligible for inclusion, 11,953 subjects had newly diagnosed mild chronic periodontitis (MCP), and 40,775 subjects had newly diagnosed severe chronic periodontitis (SCP). Two 1:1 propensity score matched cohorts were created with 8,624 patients each in the MCP and SCP groups. To analyze the risk of dementia, a Cox proportional-hazard model was used to calculate hazard ratios with 95% confidence intervals (CIs). RESULTS In the Kaplan-Meier curve, the disease-free probability was significantly lower in the SCP group than in the MCP group (p for log-rank=0.001). In the multivariable-adjusted model, the HR for the occurrence of dementia in the SCP group compared to the MCP group was 1.15 (95% CI, 1.04 to 1.27; p=0.009). A subgroup analysis revealed a significant association between dementia and the severity of periodontitis, especially in subjects who were male, aged ≥70 years, and had comorbidities. CONCLUSIONS Reducing the severity of chronic periodontitis can help to reduce the risk of dementia. Therefore, it is necessary to aggressively conduct early dementia-prevention programs for males under the age of 70 that include dental health to prevent the progression of periodontitis from mild to severe.
The Accuracy of Distal Clavicle Fracture Classifications—Do We Need an Amendment to Imaging Modalities or Fracture Typing?

Background: Despite its fair-to-moderate reliability, the “modified Neer classification” is widely accepted and used. The purpose of this study was to reevaluate its applicability. Methods: Of n = 59 patients with distal clavicle fractures, fractures were classified on standard radiographs. Afterwards, an MRI examination was performed, and fractures reclassified. The primary outcome parameter was quantifying the rate of misclassification. The secondary outcome parameters were the evaluation of the ligamentous injury constellations. Results: In all cases, the fracture course and ligamental integrity could be assigned to the fracture type. Correction of the classification was necessary in n = 5 (8.5%) cases. In n = 3 (5%) cases, a correction was necessary from Neer I to Craig IIc and thus from conservative to operative treatment. Mean coracoclavicular distance (CCD) in Neer I was 10.2 ± 2.1 mm versus 14.2 ± 3.9 mm in Craig IIc (p = 0.02). The mean fracture angle in Neer I was 25.1 ± 3.3° versus 36.8 ± 4.4° in Craig IIc (p = 0.02). Conclusion: Cross-sectional imaging resulted in higher precision. Nevertheless, recommendations remain for standard radiographs. The CCD and fracture angle should be considered. An angle of >30° can be assumed as a parameter of instability. A previously undescribed fracture type does not seem to exist. The modified Neer classification is an appropriate and complete fracture classification.
High performance of privacy-preserving acute myocardial infarction auxiliary diagnosis based on federated learning: a multicenter retrospective study

Background Multicenter medical research is becoming a new trend. However, interagency data privacy security protection has become a major bottleneck of multicenter research. Therefore, to overcome this privacy protection issue, the aim of the present study was to apply a self-developed privacy-preserving machine learning framework for researchers who can build models on medical data from multiple sources, while providing privacy protection for both sensitive data and the learned model. Methods Based on Arya, a novel privacy computing platform developed by Healink, we constructed a privacy-preserving federated learning (FL) model using the fully connected neural network with datasets from 2–3 individual medical institutions. In the dataset, 80% of records were used for joint modeling on acute myocardial infarction (AMI) diagnosis. Modeling efficacy was evaluated with the remaining 20% of records. As the control, 1,500 medical records from 1 medical institution were used for single-center modeling and efficacy evaluation. During the process, the original data were still kept in individual hospital without moving or transferring out of the hospitial. The diagnostic efficacy (sensitivity, positive predictive value, and accuracy) was evaluated. Results Our privacy-preserving FL model gives reliable AMI diagnostic efficacy. Three-center modeling (79% sensitivity, 88% positive predictive value, and 82.3% accuracy) and two-center modeling (77.8% or 77.6% sensitivity, 86.7% or 85.30% positive predictive value, and 81% or 79.7% accuracy) achieved relative high diagnostic efficacy; and single-center modeling achieved relative low diagnostic efficacy (76% sensitivity, 84.7% positive predictive value, and 79% accuracy). Conclusions The Arya privacy computing platform is efficient and practical for the FL model, which could promote multicenter medical research securely without sacrificing diagnostic efficacy.
Multigap Superconductivity in the Ferromagnetic Superconductor UCoGe Revealed by Thermal Conductivity Measurements

We performed thermal conductivity measurements on a single crystal of the ferromagnetic superconductor UCoGe under magnetic field. Two different temperature dependencies of the thermal conductivity are observed, for : linear at low magnetic field and quadratic for magnetic field larger than 1 Tesla. At the same field value, a plateau appears in the field dependency of the residual term of thermal conductivity. Such observations suggest a multigap superconductivity with a line of nodes in the superconducting gap.
Exercise Training Attenuates Hypertension via Suppressing ROS/MAPK/NF-κB/AT-1R Pathway in the Hypothalamic Paraventricular Nucleus

Background: Aerobic exercise training (ExT) is beneficial for hypertension, however, its central mechanisms in improving hypertension remain unclear. Since the importance of the up-regulation of angiotensin II type 1 receptor (AT-1R) in the paraventricular nucleus (PVN) of the hypothalamic in sympathoexcitation and hypertension has been shown, we testified the hypothesis that aerobic ExT decreases blood pressure in hypertensive rats by down-regulating the AT-1R through reactive oxygen species (ROS)/mitogen-activated protein kinase (MAPK)/nuclear factors κB (NF-κB) pathway within the PVN. Methods: Forty-eight male Sprague-Dawley (SD) rats were assigned to the following groups: sham operation (SHAM) + kept sedentary (Sed), SHAM + exercise training (ExT), two kidney-one clamp (2K1C) + Sed, and 2K1C + ExT groups. Results: The 2K1C + Sed hypertensive rats showed higher systolic blood pressure (SBP), upregulated ROS, phosphorylated (p-) p44/42 MAPK, p-p38 MAPK, NF-κB p65 activity, and AT-1R expression in the PVN, and increased circulating norepinephrine (NE) than those of SHAM rats. After eight weeks of aerobic ExT, the 2K1C + ExT hypertensive rats showed attenuated NE and SBP levels, suppressed NF-κB p65 activity, and reduced expression of ROS, p-p44/42 MAPK, p-p38 MAPK, and AT-1R in the PVN, relatively to the 2K1C + Sed group. Conclusions: These data are suggestive of beneficial effects of aerobic ExT in decreasing SBP in hypertensive rats, via down-regulating the ROS/MAPK/NF-κB pathway that targets AT-1R in the PVN, and eventually ameliorating 2K1C-induced hypertension.
Assessment of Efficacy and Safety Using PPAR-γ Agonist-Loaded Nanocarriers for Inflammatory Eye Diseases

Drug-loaded nanocarriers (NCs) are new systems that can greatly improve the delivery and targeting of drugs to specific tissues and organs. In our work, a PPAR-γ agonist loaded into polymeric NCs was prepared, stabilized by spray-drying, and tested in vitro, ex vivo, and in vivo (animal models) to provide a safe formulation for optical anti-inflammatory treatments. The NCs were shown to be well tolerated, and no signs of irritancy or alterations of the eye properties were detected by the in vitro HET-CAM test and in vivo Draize test. Furthermore, no signs of cytotoxicity were found in the NC formulations on retinoblastoma cells (Y-79) analyzed using the alamarBlue assay, and the transmittance experiments evidenced good corneal transparency with the formulations tested. The ocular anti-inflammatory study confirmed the significant prevention efficacy using the NCs, and these systems did not affect the corneal tissue structure. Moreover, the animal corneal structure treated with the NCs was analyzed using X-ray diffraction using synchrotron light. Small-angle X-ray scattering (SAXS) analysis did not show a significant difference in corneal collagen interfibrillar spacing after the treatment with freshly prepared NCs or NCs after the drying process compared to the corresponding negative control when inflammation was induced. Considering these results, the PPAR-γ agonist NCs could be a safe and effective alternative for the treatment of inflammatory ocular processes.
Particles in the nebular midplane: Collective effects and relative velocities

Abstract– In the absence of global turbulence, solid particles in the solar nebula tend to settle toward the midplane, forming a layer with enhanced solids/gas ratio. Shear relative to the surrounding pressure‐supported gas generates turbulence within the layer, inhibiting further settling and preventing gravitational instability. Turbulence and size‐dependent drift velocities cause collisions between particles. Relative velocities between small grains and meter‐sized bodies are typically about 50 m s−1 for isolated particles; however, in a dense particle layer, collective effects alter the motion of the gas near the midplane. Here, we develop a numerical model for the coupled motions of gas and particles of arbitrary size, based on the assumption that turbulent viscosity transfers momentum on the scale of the Ekman length. The vertical distribution of particles is determined by a balance between settling and turbulent diffusion. Self‐consistent distributions of density, turbulent velocities, and radial fluxes of gas and particles of different sizes are determined. Collective effects generate turbulence that increases relative velocities between small particles, but reduce velocities between small grains and bodies of decimeter size or larger by bringing the layer’s motion closer to Keplerian. This effect may alleviate the “meter‐size barrier” to collisional growth of planetesimals.
SMOFlipid Impact on Growth and Neonatal Morbidities in Very Preterm Infants

The soybean oil, medium-chain triglycerides, olive oil, and fish oil lipid (SMOFlipid) is increasingly being used worldwide without definite evidence of its benefits. We examined the effect of SMOFlipid on growth velocity and neonatal morbidities in very preterm infants. Very preterm infants who received soybean-based lipid emulsion between January 2015 and 2018 were compared with those who received SMOFlipids between 2019 and January 2022 in our neonatal tertiary center. Linear regression analysis was conducted to analyze the association between type of lipid emulsion and growth velocity. Modified log-Poisson regression with generalized linear models and a robust variance estimator (Huber–White) were applied to adjust for potential confounding factors. A total of 858 infants met our inclusion criteria. Of them, 238 (27.7%) received SMOFlipid. SMOFlipid was associated with lower growth velocity between birth and 36-week corrected gestational age compared with intralipid Δ weight z-score (adjusted mean difference (aMD) −0.67; 95% CI −0.69, −0.39). Subgroup analysis indicated that mainly male infants in the SMOFlipid–LE group had a lower Δ weight z-score compared to those in the intralipid group (p < 0.001), with no difference observed in females (p = 0.82). SMOFlipid was associated with a lower rate of bronchopulmonary dysplasia (BPD) (aRR 0.61; 95% CI 0.46, 0.8) and higher rate of late-onset sepsis compared with intralipid (aRR 1.44; 95% CI 1.22–1.69). SMOFlipid was associated with lower growth velocity and BPD but higher rate of late-onset sepsis—it is a double-edged sword.
Tryptamine, a Microbial Metabolite in Fermented Rice Bran Suppressed Lipopolysaccharide-Induced Inflammation in a Murine Macrophage Model

Fermentation is thought to alter the composition and bioavailability of bioactive compounds in rice bran. However, how this process affects the anti-inflammatory effects of rice bran and the bioactive compounds that might participate in this function is yet to be elucidated. This study aimed to isolate bioactive compounds in fermented rice bran that play a key role in its anti-inflammatory function. The fermented rice bran was fractionated using a succession of solvent and solid-phase extractions. The fermented rice bran fractions were then applied to lipopolysaccharide (LPS)-activated murine macrophages to evaluate their anti-inflammatory activity. The hot water fractions (FRBA), 50% ethanol fractions (FRBB), and n-hexane fractions (FRBC) were all shown to be able to suppress the pro-inflammatory cytokine expression from LPS-stimulated RAW 264.7 cells. Subsequent fractions from the hot water fraction (FRBF and FRBE) were also able to reduce the inflammatory response of these cells to LPS. Further investigation revealed that tryptamine, a bacterial metabolite of tryptophan, was abundantly present in these extracts. These results indicate that tryptamine may play an important role in the anti-inflammatory effects of fermented rice bran. Furthermore, the anti-inflammatory effects of FRBE and tryptamine may depend on the activity of the aryl hydrocarbon receptor.
Personality traits: Support for survive in pandemic Covid-19 for SMEs

Purpose – Small and Medium Enterprises (SMEs) play an important role in the Indonesian economy. However, the Covid-19 pandemic has hampered the economic sector, companies must be able to create the best market opportunities one way through which entrepreneurial personality traits and skills can influence the market and entrepreneurial orientation. Therefore, it is important to know the important role of the personality and skills of SME owners in responding to this situation. Based on this, this study aims to examine the relationship between personality traits, entrepreneurial orientation, market orientation and performance.Methodology – This study uses a survey with a structured questionnaire with a total of 103 SMEs owners in Indonesia.Findings – This study shows that the ability to negotiation skill and risk taking has a significant effect on both entrepreneurial orientation and market orientation, but optimism and locus of control have no effect on market orientation and orientation.Implications – This study promises to examine how the positive role of personality traits here can help managers view any crisis in a new perspective. As for the managerial implications a manager can use the influence of their personality to inspire and mobilize their team to work effectively to achieve common goals.Originality – This research is to provide a useful view for SMEs owners, it is important to be entrepreneurship and market oriented in order to improve SMEs performance and increase awareness of the importance and adopting new technology as an effort to deal with the Covid-19 and anticipate the economy in the future.
Experimental Investigation of Optimization of Machining Parameters in Abrasive Water Jet Machining

Now a days, Non-Conventional Machining process is gaining more attention by the researchers. Abrasive Water jet machining (AWJM) is one of such machining process where material is removed with abrasive slurry as cutting tool. The present work discuss about the development of an optimal solution for minimizing surface roughness using a response surface methodology (RSM) while machining of EN grade steel. The machining parameters considered for the study are Abrasive Grain Size (AGS) and Hydraulic Pressure (HP) and Stand Off Distance (SOD) and the Abrasive Flow Rate (AFR). The response parameter is surface roughness (Ra). The experiments are performed based on the Box-Behnken design. Additionally, the significance of the developed optimization design has been identified using analysis of variance (ANOVA). Finally, the validity and adequacy of the developed model are done through confirmation tests. Key Words: Abrasive Water jet Machining, Response Surface Methodology, Optimization, ANOVA
Use of quantum dot nanocrystals for spectrally encoded optical data storage

In this paper, we demonstrate the spectral encoding capability of quantum dot nanocrystals (QDs). We mixed two different sizes of QDs in a resin, and two-photon excitation at various wavelengths showed that the relative intensities of the fluorescence from two QDs varied significantly. Such a difference in level of absorption at different wavelengths allows one to record information only on one size of QDs, without affecting the other sized QDs. This property can be applied to optical data storage, so that storage density can be greatly improved.