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Design, synthesis, and in vitro evaluation of a carbamazepine derivative with antitumor potential in a model of Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) is a significant concern in both pediatric and adult demographics. Despite 156 approved cancer therapies based on small molecules, a mere five apply to all types of leukemia. Unfortunately, adherence to these treatments is low due to adverse side effects. Consequently, there is an urgent need to identify more effective treatment options for ALL. This study presents a potential solution. We have designed over fifty analogs of carbamazepine, utilizing a combination of ligand-based and structure-based drug design methodologies. Among these analogs, we identified the CR80 analog, which demonstrated predicted binding values of -8.66 kcal/mol against beta-tubulin, a favorable LogP, and IC50 values suitable for in vitro evaluation. The CR80 compound was synthesized with a yield of 50% and subsequently assessed in vitro against the U-937 cell line. It obtained an IC50 value of 0.8 micromolar to 1 micromolar and a selectivity index of two, thus marking it as a promising candidate for in vivo studies.

Hybrid optimization driven fake news detection using reinforced transformer models

Thermodynamics for reduced models of polymer aggregation based on maximum entropy principle

Polymeric aggregates play a significant role in biology and chemical engineering. In order to make a clear description of their underlying formation procedure, simplified models are crucial because the original mass-action equations involve numerous variables, complicating analysis and understanding. While the dynamical aspects of simplified models have been widely studied, their thermodynamic properties are less understood. In this study, we explore the Maximum Entropy Principle (MEP)-reduced models, initially developed for dynamical analysis, from a brand-new thermodynamic perspective. Analytical expressions, along with numerical simulations, demonstrate that the discrete MEP-reduced model strictly retains laws of thermodynamics, which holds true even when the aggregate size transits from discrete values to continuous real numbers. Our findings not only clarify the thermodynamic consistency between the MEP-reduced models and the original models of polymeric aggregates for the first time but also suggest avenues for future research into the model-reduction thermodynamics.

Effects of school menstrual hygiene management, water, sanitation, and hygiene interventions on girls’ empowerment, health, and educational outcomes: Lasta district, Amhara regional state, Ethiopia

This study assessed the effects of school-based menstrual hygiene management (MHM) and water, sanitation, and hygiene (WASH) interventions on the empowerment, health, and educational outcomes of menstruating girls using cross-sectional and experimental designs. It examined whether access to MHM education and WASH facilities could enhance girls’ self-confidence, physical, emotional, and social health, class attendance, and academic performance. The results showed significant improvements in empowerment at intervention schools, with 54% of girls feeling confident purchasing sanitary products, compared to 18% in control schools, indicating better emotional well-being. Additionally, 21% and 22% of girls in intervention schools felt comfortable discussing MHM with boys and mothers, respectively, compared to just 9% in control schools, reflecting improved social health. Regarding physical health, 51% of menstruating girls in intervention schools practiced genital hygiene three to four times a day, compared to 33% in control schools. Educational outcomes were also improved, with 68% of girls in intervention schools attending class during menstruation, compared to 30% in control schools, and 78% reporting adequate study time at home, compared to 41% in control schools. However, no significant difference in academic performance was found between the two groups. Overall, the findings suggest that school-based MHM and WASH interventions can significantly empower menstruating girls, improve their physical, emotional, and social health, and reduce menstrual-related absenteeism.

Artificial intelligence alert system based on intraluminal view for colonoscopy intubation

Li4F4−: Planar tetracoordinate fluorine in a highly viable binary mono-anionic cluster

Planar hypercoordinate fluorine is elusive due to the high electronegativity of fluorine, which restricts electron delocalization. Despite some progress, planar tetracoordinate fluorine (ptF) anionic species with simple components suitable for photoelectron spectroscopy have not yet been reported. Herein, we introduce the first binary mono-anionic Li4F4− cluster containing a ptF center with C2v symmetry. At a given level of theory, it is a global minimum (GM) structure with good dynamic stability and significant barriers to interconversion into the lowest energy isomers. It is noteworthy that the GM of the neutral Li4F4 species adopts a cube configuration similar to that of the typical bulk lithium fluoride crystal structure rather than a planar shape. The stability of the ptF is dominated by electrostatic interactions, supplemented by a weak covalent component rather than any aromaticity. The cluster is a highly viable species and a promising candidate for experimental detection and characterization.

Needs satisfaction and Online Self-Regulated Learning among chinese undergraduates

The increasing popularity of online courses has highlighted the importance of online self-regulated learning (OSRL). However, its use among undergraduates remains challenging. Based on self-determination theory, this study examined whether satisfying three basic psychological needs (i.e., autonomy, competence, and relatedness) could foster the engagement of Chinese undergraduates (N = 381) in OSRL. Data were collected from an online questionnaire, which included a revised Online Self-Regulated Learning Questionnaire, a scale to measure need satisfaction, and demographic information items. Descriptive analyses, confirmatory factor analyses and structural equation modeling were conducted. The results revealed that overall need satisfaction was positively associated with the use of OSRL strategies. Specifically, satisfying autonomy was positively associated with the use of resource management strategies. Feeling competent was positively associated with most OSRL strategies, except for time management and help seeking. A sense of relatedness was positively associated with self-evaluation, task strategies, and help seeking. These findings underscore the unique role of each need in promoting OSRL. Therefore, designers and instructors of online courses should cater to the specific needs of undergraduates to enhance their use of targeted OSRL strategy(ies).

Harnessing deep learning to monitor people’s perceptions towards climate change on social media

Bubble phase induced by odd interactions in chiral systems

We study a chiral system of particles subject to both odd interactions and standard repulsive interactions. The interplay between oddness and inertia induces a non-equilibrium phase transition from a homogeneous to a non-homogeneous phase, characterized by the emergence of bubbles due to odd interactions. This phenomenon occurs in the absence of attractions and results from the competition between pressures, arising from particle repulsion, which tends to shrink the bubble, and an effective surface force that promotes its expansion. The latter is an effective centrifugal force associated with the circular motion of particles along the bubble’s surface, driven by transverse interactions. As a signature of the phase transition, the system exhibits vortex structures and oscillating spatial velocity correlations, which emerge near the analytically predicted transition point. Our findings can be tested in granular experiments involving odd interactions, such as spinners and active granular particles, and could be crucial for characterizing the emergent properties of metamaterials.

Spatiotemporal heterogeneity of bicycle ridership based on GTWR model

As a low-carbon, green and environmentally friendly mode of travel, bicycles possess significant advantages in short-distance trips. In previous studies on the relationship between the built environment and bicycle behavior, the built environment variable only took into account the number or density of facilities. However, due to their different grades and formats, the attractions of similar facilities of the same size to residents vary considerably. Therefore, this paper constructs a comprehensive index of POI (Point of Interest) facility quality to reflect the influence of the number of facilities and preferences on bicycle trips. In addition, two types of riding safety indicators, namely the proportion of non-isolation bars and the proportion of non-motor vehicle lane parking, are added to the road safety facilities. On this basis, GWR and GTWR models are established to explored the temporal and spatial distribution characteristic of cycling, and identifies the relationship between cycling behavior and built environments based on 2022 Daily Trip Survey in Xianyang, China. The model results demonstrate the following: (1) The GTWR model exhibits a better fit compared to the GWR model. (2) There are significant differences between the urban central area and the marginal area, which verifies that similar facilities have diverse impacts on the cycling frequency in distinct regions. (3) The promoting or inhibiting effects of the urban built environment on the cycling frequency are highly congruent with the temporal characteristics of commuting, and these effects typically reach their maximum during commuting rush hours. (4) Cycling safety facilities constitute a significant factor influencing the cycling frequency. These results can not only offer guidance for urban planning and design but also foster the sustainable development of green transportation.

Author Correction: Low intensity pulsed ultrasound alleviates synovial fibrosis in osteoarthritis via the PI3K/AKT pathway

Hydrogen scrambling and high propensity for multiple neutral emissions from 1,3-butadiene dication

The two-body dissociation of the dications formed after double ionization of the smallest conjugated diene, the 1,3-butadiene, C4H6, is studied using the coincidence time-of-flight technique and quantum chemistry calculations. The dication was formed by ion-impact ionization using energetic Xe3+ projectiles. Our results show that butadiene dication has a high propensity of neutral particle emission (H/H2/C2H2) prior to two-body dissociation into two singly charged fragments. The asymmetric two-body breakup, after the emission of neutral fragments from parent butadiene dication, is observed to be twice as probable as the asymmetric two-body breakup of intact butadiene dication. Our experimental results suggest that multiple structures may be formed for several different precursor dications formed after loss of neutral particles, which is indicative of the strong role of hydrogen scrambling. The internal energy dependence and time evolution of the interplay between neutral particle emission, hydrogen scrambling, and hydrogen migration are explored using ab initio molecular dynamics simulations to support the experimental observations.

Outcomes and predictors of in-hospital mortality among patients admitted to the intensive care or step-down unit after a rapid response team activation: A retrospective cohort study

Introduction It has been demonstrated that the implementation of rapid response teams (RRT) may improve clinical outcomes. Nevertheless, predictors of mortality among patients admitted to the intensive care unit (ICU) or to the step-down unit (SDU) after a RRT activation are not fully understood. Objective To describe clinical characteristics, resource use, main outcomes, and to address predictors of in-hospital mortality among patients admitted to the ICU/SDU after RRT activation. Methods Retrospective single-center cohort study conducted in a medical-surgical ICU/SDU located in a private quaternary care hospital. Adult patients admitted to the ICU or SDU between 2012 and 2020 were compared according to in-hospital mortality. A multivariate logistic regression analysis was performed to identify independent predictors of in-hospital mortality. Results Among the 3841 patients included in this analysis [3165 (82.4%) survivors and 676 (17.6%) non-survivors], 1972 (51.3%) were admitted to the ICU and 1869 (48.7%) were admitted to the SDU. Compared to survivors, non-survivors were older [76 (64–87) yrs. vs. 67 (50–81) yrs.; p < 0.001], had a higher SAPS 3 score [64 (56–72) vs. 49 (40–57); p < 0.001], and had a longer length of stay (LOS) before unit admission [8 (3–19) days vs. 2 (1–7) days; p < 0.001). Non-survivors used more non-invasive ventilation (NIV) (42.2% vs. 20.9%; p < 0.001), mechanical ventilation (MV) (36.7% vs. 9.3%; p < 0.001), vasopressors (39.2% vs. 12.3%; p < 0.001), renal replacement therapy (15.5% vs. 4.3%; p < 0.001), and blood components transfusion (34.9% vs. 14.0%; p < 0.001). Independent predictors of in-hospital mortality were the SAPS 3 score, the Charlson Comorbidity Index, LOS before unit admission, immunosuppression, respiratory rate < 8 or > 28 ipm criteria for RRT activation, RRT activation during the night shift, and the need for high-flow nasal cannula, NIV, MV, vasopressors, and blood components transfusion. Conclusion Multiple factors may affect outcomes of ICU/SDU-admitted patients after RRT activation. Therefore, efforts should be made to boost RRT effectiveness to improve patient safety.

Curcumin attenuates neuroinflammation and improves cognitive function in a rat model of febrile convulsions

Many-body approach to projective solution of generalized operators: Formulation and application to quantum computing

In this paper, we propose a novel many-body approach for determining the amplitudes of generalized operators in a projection-based formalism. To implicitly account for the effects of higher-order excitations, we begin with the well-established double-exponential coupled-cluster (CC) ansatz, parametrized by both one- and two-body excitation operators, complemented by a set of vacuum-annihilating two-body generalized operators with effective excitation rank of one. A systematic formalism is developed that effectively bypasses the constraints due to the vacuum-annihilation property of the generalized operators toward a set of closed-form residual equations for their optimization. Such a strategy requires the removal of the underlying redundancy in high-rank excited determinants, generated due to the presence of the generalized operators in the ansatz, by projecting them onto an internally contracted lower-dimensional manifold. This many-body formalism is integrated with the near-term projective quantum eigensolver (PQE) framework that leverages the conventional CC-like residual minimization to iteratively decouple the excited manifold from the reference. With the application of several molecular systems within PQE architecture, we demonstrate that the developed methodology enables us to achieve similar accuracy to the disentangled unitary coupled cluster with singles, doubles, and triples ansatz while utilizing an order of magnitude fewer quantum resources. Furthermore, when simulated under stochastic Gaussian noise or depolarizing hardware noise, our method shows significantly improved noise resilience compared to the other members of PQE family and the state-of-the-art variational quantum eigensolver.

The canine vaginal microbiome during heat and fertility in healthy breeding dogs

A healthy and balanced vaginal microbiome is often thought to be an important prerequisite for successful breeding and healthy litters. Previous studies investigating the influence of canine vaginal bacteria on fertility mostly relied on aerobic culturing. In recent years, culture-independent methods, such as next-generation sequencing (NGS), have become popular. With the ability to analyze the microbiome as a whole, research in this field has made notable advances. This is the first study to correlate NGS data of the canine vaginal microbiome in heat with fertility data. Healthy breeding bitches (n=80) presented for routine pre-breeding examination were sampled during early heat and mated after ovulation. A vaginal sample was taken for NGS analysis and microbiological culture. Additionally, a blood sample was collected. Fertility data (mating, pregnancy, delivery, litter size) were assessed. NGS revealed a diverse microbiome in all the samples. Bioinformatics and statistical analysis did not provide evidence of larger differences in the microbiome of those bitches that became pregnant and those that did not.

Innovative cross-layer defense mechanisms for blackhole and wormhole attacks in wireless ad-hoc networks

Abstract Wireless ad-hoc networks operate independently of existing infrastructure, using devices like access points to connect end-user computing devices. Current methods face issues such as low detection accuracy, structural deviation, and extended processing times. This paper proposes a cross-layer approach that leverages knowledge from the physical and Medium Access Control (MAC) layers, which is then shared with higher layers to effectively mitigate wormhole and blackhole attacks. A wormhole attack disrupts communication through tunneling, while a blackhole attack manipulates network traffic by impersonating the source. The proposed cross-layer framework integrates the network, MAC, and physical layers, and is independent of specific network protocols. The physical layer handles channel interference, the network layer manages process handling, and the MAC layer oversees bandwidth information and tracks failed transmissions. Performance metrics are measured in seconds. The Enhanced Support Vector Machine (E-SVM) algorithm, implemented using NS3 software, demonstrates superior performance compared to traditional SVM techniques across multiple metrics, including average energy consumption, average remaining energy, packets received, packet delivery ratio, delay, jitter, throughput, normalized overhead, dropping ratio, and goodput. Simulation results show that E-SVM achieves a 12.5% dropping ratio, 98.459% energy consumption, and an 89.2879% packet delivery ratio, outperforming existing SVM techniques across various network sizes.

Exploring the high sensitivity of DFT thermochemistry for protonation states of a ferredoxin model complex [CH3S4Fe2IIIS2H]−

Density functional theory (DFT) thermochemistry of 3d transition-metal complexes is well-known to be sensitive to the amount of exact Hartree–Fock exchange incorporated into the exchange–correlation functional. For example, relative energies of different protonation states of iron–sulfur complexes may vary by hundreds of kJ/mol among different DFT methods. In the present study, we examine the relative energies of four protonation isomers of the [CH3S4Fe2IIIS2H]− [2Fe–2S] ferredoxin model. Compared to many-body ab initio phaseless auxiliary-field quantum Monte Carlo with multi-Slater determinant trial wavefunctions and fully connected singles and doubles coupled-cluster with perturbative triples methods, the r2SCAN12-D4, B3LYP-D4, and B97-1-D3(OP) approaches perform the best. We also demonstrate that density-corrected DFT on top of KS-CCSD electronic densities provides reliable results with the r2SCAN functional. Moreover, the direct random phase approximation on top of the TPSSh, O3LYP, and r2SCAN12 hybrid functionals performs well.

Environmental persistence of nontyphoidal Salmonella in an urban informal settlement in Nairobi, Kenya

Non-typhoidal Salmonella (NTS) presents a considerable health threat to children in low-resource settings, where clean water, sanitation, and hygiene are often inadequate. However, the environmental factors influencing NTS persistence and spread remain poorly understood. We utilized a case-control approach to investigate environmental factors associated with NTS infection in children living in Nairobi’s informal settlements between August 2022 and July 2023. Stool samples were collected from febrile children, with or without diarrhea, who visited healthcare facilities. The study included 42 laboratory-confirmed NTS-positive cases and 42 NTS-negative children from the same community. Environmental samples, including drinking water, open drains, soil, and household effluent, were collected from both case and control households, in addition to raw sewage from main sewer-line convergence points. Conventional microbiological culture and quantitative Polymerase Chain Reaction techniques were employed for NTS detection, with genomic sequencing used for strain characterization. Environmental samples from case households showed a higher NTS contamination rate of 33.3% (42/126) compared to control households of 7.2% (9/126). Higher odds of NTS infection in children were associated with household environmental factors, particularly exposure to household effluent (OR = 7.7, 95% CI: 2.18–34.82, p = 0.0005), drinking water (OR = 6.4, 95% CI: 1.57–37.76, p = 0.0055), and soil (OR = 5.4, 95% CI: 1.01–54.28, p = 0.0485). Genomic analysis revealed a common strain, Salmonella Enteritidis ST11, in clinical and environmental isolates. These findings highlight the plausible role of the household environment as a reservoir for NTS, perpetuating infection cycles within the community. Addressing this challenge requires a multifaceted approach, including improved sanitation infrastructure, environmental monitoring, and integrated public health interventions to reduce NTS exposure and transmission in high-risk populations.

Synthesis, characterization and bio-evaluation of novel series of pyrazoline derivatives as potential antifungal agents