bluuebunny/crossref_metadata_2025 huggingface dataset:
Relación entre consumo de sustancias y agresividad, problemas académicos, familiares y conductuales en adolescentes españoles
Authors: Vegas María Isabel , Mateos-Agut Manuel , De la Fuente-Anuncibay Raquel , Pineda-Otaola Pedro J. , Sebastián-Vega Carlota
Published: July 2024

Introducción. El consumo de sustancias psicoactivas y la agresividad en la adolescencia, son dos graves problemas sociales, con repercusiones a nivel sanitario, escolar y familiar. Objetivo. Estudiar la relación entre agresividad y consumo de sustancias en población adolescente, y analizar las diferencias en consumo, entre adolescentes con bajo rendimiento académico, problemática familiar o conductual. Método. Participaron 1196 adolescentes de Castilla y León, entre 14 y 18 años (50% mujeres), procedentes de 23 centros educativos, 10 grados universitarios y 18 centros de menores. Se utilizó el Cuestionario de Agresividad de Buss y Perry (BPAQ). Resultados. El consumo de sustancias se relacionó, fundamentalmente, con la agresividad física y la ira del adolescente. La agresividad física aumentó progresivamente, al crecer el consumo de cualquier sustancia. La ira era mayor en todos los consumidores, intensificándose en caso de frecuentes atracones de alcohol. La hostilidad únicamente correlacionó con el consumo de tabaco y cannabis. Asimismo, los adolescentes con bajo rendimiento académico o problemática familiar, fumaban más tabaco y cannabis que el grupo general; los adolescentes con graves problemas conductuales, presentaban más atracones de alcohol y mayor consumo intenso de cannabis y tabaco. Conclusiones. Estos resultados refuerzan la importancia de la prevención, a nivel socio-educativo y familiar.
Ethical Studies at the Institute of Philosophy (1920s–1980s)
Authors: Apressyan Ruben G. ,   RAS Institute of Philosophy
Published: July 2024

The article presents through an analytical description of the main stages, directions, key events and figures of ethical studies at the Institute of Philosophy. The review begins with a portrayal to the scientific attitudes and expectations of the Institute of Scientific Philosophy (ISPh). Due to the extremely unfavorable political situation, they were not implemented, but their reconstruction is interesting for understanding the research po­tential that the ISPh had had before its leading fellows were expelled from the Soviet Russia. Left alone with themselves in the ISPh, Marxist philosophers soon involved in acute ideological squabbles, which in fact left no room for philosophy in the true sense of the word. After the debates of the late 1920s – early 1930s, the Institute of Phi­losophy of the Soviet Academy of Sciences (IPhAN) returned to ethical problematique only twenty years later. The article presents some episodes of the early history of ethical studies in IPhAN, which have long remained in oblivion. The article recognizes that theoretically significant in the development of ethics in the IPhAN, as well as in the So­viet ethics in general, was everything that contributed to its dedogmatization and the de­velopment of theoretical reliability, which was ultimately set up by the internal compati­bility of basic definitions, namely: of the essence of morality, its functionality and struc­ture. The vicissitudes of the process of growth of the theoretical level of ethics are shown on the material of the discussion about the possible universality of moral de­mands. This process did not acquire a comprehensive character for the Soviet ethics, but what was achieved marked a cardinal turn in ethical theory and became key in its forty-year dynamics of the second half of the 20th century.
Usury in Theological and Canonical Thought, and Confessional-Cultural Practices of the Early Modern Times
Authors: Korzo Margarita A. ,   RAS Institute of Philosophy
Published: July 2024

The understanding of usury in Western theological and canonical thought was determined by the texts of the Holy Scriptures, the philosophical ideas of ancient thinkers, but also by the socio-economic realities of a particular epoch. The meaning of the Latin term “usura” underwent significant changes, narrowing over time and limiting itself to certain contracts (mutuum). Usury had a moral dimension, since the economic behavior of Christians was significant for the salvation of the soul. From a sin primarily against the commandment of love, “usura” evolves into a sin against justice. Usury also had a social dimension: the word “usurer” could stigmatize those who did not belong to a particular social (profes­sional) or ecclesiastical community. In the era of confessional demarcation of the Early Modern times, each of the denominations sought to formulate a new economic ethics that would be more in line with current economic practices and trends. The apparent similarity of the different confessional positions did not always indicate the identity of the arguments in favor of the permissibility of moderate usurious interest. At the same time, many Protes­tant theologians, despite the nuances of their positions, can identify a common point in their approach to usury and related problems that distinguished them from Catholics: the empha­sis is rather on the individual conscience of the Christian, that determines the economic be­havior of the individual, than on external regulation, although the secular authorities retain significant levers of control over lending activities.
Human Nature as the Foundation of Morality in Gilles Deleuze’s “Empiricism and Subjectivity”
Authors: Kosorukova Alexandra A. ,   RUDN University, Mikhan Roman I. ,   RUDN University
Published: July 2024

The article examines the moral system presented by Gilles Deleuze in his early work “Em­piricism and Subjectivity: An essay on Hume’s Theory of Human Nature”. Based on Hume’s philosophy, Deleuze develops a moral and social system that is grounded in human nature. The article analyzes a coherent system that outlines the principles of human na­ture in relationship to a theory of knowledge, provides an explanation for moral intuitions and the construction of a moral scheme, and sets principles for the formation of society. In the article, it was revealed how Deleuze understood empiricism and subjectivity and how these concepts change our understanding of human nature. It was demonstrated how the principles of human nature explain our moral intuitions, and why sympathy is the basis for morality and society. It has been reasoned why a person’s disposition for sympathy and his belonging to the community makes moral egoism impossible. In Hume’s philosophy it­self one can already find principles for the formation of society based on human sympathy and creativity. According to Deleuze, Hume sees in the social contract and the law a negativ­ity that restrains our freedom and our desires. Therefore, in search of a positive means to form a society, Hume turns to social institutions that are possible due to sympathy. To build a successful society, it is necessary to resort to moral schematism in the form of establishing general rules for all members of society. Already in the work on Hume, we can find several topics that Deleuze is interested in, and which he will develop in the future. First of all, a new anthropology, where much attention is paid to affects and processuality, as well as consideration of society through the creativity of human nature.
The Problem of Groundless Shame in Adam Smith’s The Theory of Moral Sentiments
Authors: Prokofyev Andrey V. ,   RAS Institute of Philosophy
Published: July 2024

The paper deals with Adam Smith’s statement and solution of the problem of groundless shame, i.e. shame that is not connected with actual violations of moral principles and arises due to the fact that people around the agent condemn him or consider his situation shame­ful. The problem is posed by A. Smith in the course of the discussion of four natural drives: the love of praise, the love of praise-worthiness, the dread of blame, the dread of blame-wor­thiness. Smith notices a remarkable asymmetry among them: undeserved praise gives the wise and virtuous man no pleasure, while undeserved blame causes him quite intense suffering. It “throws a shadow of disgrace and dishonor upon his character”, makes him feel “humbled”, etc. In some passages of The Theory of Moral Sentiments, A. Smith, if not approving of such feeling, at least recommends taking all measures to prevent undeserved blame and ensuing shame. In other passages he treats the dependence of a moral agent’s feelings and behavior on undeserved blame as an apparent moral weakness (“slavery to the world”). In the former case, A. Smith discusses mainly undeserved blame based on erroneous attribution of actions and motives, in the latter case, he means the blame based on distorted or outright wrong evaluation criteria. Two important examples of the shame evoked by using bad criteria are the shame of poverty and the shame of practicing “unfashionable virtues”. A. Smith, unlike David Hume, considers the shame of poverty and the corresponding pride in wealth, despite their deep roots in human nature and apparent societal benefits, groundless. The shame of practicing “unfash­ionable virtues” has this status by definition.
Ethical and Philosophical Problems of Designing Artificial Moral Agent
Authors: Ignatev Andrei G. ,   School of Philosophy and Cultural Studies, HSE University
Published: July 2024

The article considers objective preconditions and reasons for the creation of an artificial moral agent (AMA), offers arguments both in favour of the development of such projects and demonstrating the limited capabilities of artificial intelligence systems in possessing the sub­jectness necessary for making moral decisions. First of all, disclosing the problem in terms of moral philosophy, approaches to the notion of “artificial moral agent” are presented, some con­cepts that hypothetically could provide the realisation of the so-called “machine morality” are discussed, and the initial conditions/criteria for AMA are outlined. The IMA problem is traced in relationship to theories in the fields of analytical ethics and philosophy of technology. On the basis of such an analysis the directions of research and scientific-experimental work on the creation of AMA are proposed. The thesis is justified about the failure of technical reali­sation of a universal, human-like AMA with the ability to solve complex, diverse moral dilem­mas and tasks, to act in a wide and diverse field of moral situations. In this regard, it is pro­posed to use new terms – computational moral quasi-agent (MQA), and when decisions are made on the basis of human-machine interaction – convergent or hybrid moral agent (HMA). In the conditions of insufficiently developed theoretical basis and the presence of risks of MQA implementation, the author proposes a balanced, phased development of projects based on a subject-oriented, contextual approach (SOCA). Such an approach implies responsi­ble implementation of MQA for specific types of systems (models) with a specific application task, in a specific physical or virtual environment (domain). In this case, the feasibility of de­signing MQA or HMA in a particular project should be explained, justified and proved.
Histopathologic Features of Trachea and Lungs in Chickens with Chronic Respiratory Disease
Authors: Annisa Aiza , Darmawi Darmawi , Etriwati Etriwati , Balqis Ummu , Salim M. Nur , Nazaruddin Nazaruddin , Aliza Dwinna , Aisyah Siti , Awaluddin Awaluddin , Hasan Denny Irmawati , Akmal Muslim , Helmi T. Zahrial , Asmilia Nuzul
Published: July 2024

The purpose of this case study is to determine the changes that exist in chickens infected with Chronic Respiratory disease (CRD). A broiler male chicken aged ± 40 days was found dead in a chicken basket at Ulee Kareng chicken slaughterhouse in a state of feather loss and feces attached to cloaca, on January 6th, 2023. The chicken was brought to pathology laboratory of Faculty of Veterinary Medicine, Universitas Syiah Kuala for necropsy and organ collection. Organs associated with CRD cases were trachea and lungs and histopathological preparations were carried out, stained with Haematoxylin Eosin, and observed under a microscope. The results of histopathological examination showed hemorrhage and hyperplasia of the tracheal epithelium. Hemorrhage was caused by edema which causes increased vascular permeability and epithelial cell hyperplasia occured due to the body's response to infection or inflammation. In the lungs there was bleeding due to damage to the blood vessel wall which caused increased vascular permeability, so that fluid and blood plasma come out of the blood vessels. Fibrinogen then underwent polymerization which resulted in fibrinous thrombi. Congestion happened as the result of fluid accumulation in a location that occured in a passive process so the fluid failed to escape. Because of the accumulation of fluid (congestion), the blood supply to the lung tissue is interrupted, resulting in several points of necrosis in the lungs.
Microcephaly, progressive, seizures, and cerebral and cerebellar atrophy: QARS1 new variants associated with a severe phenotype in a patient
Authors: Sakka Rania , Hamida Hayet Ben , Abdelali Mabrouk , Chaabane Amel , Zrig Ahmed , M’rad Ridha , Mekki Mongi , Monastiri Kamel
Published: July 2024

Microcephaly, progressive, seizures, and cerebral and cerebellar atrophy is a rare disease due to QARS1 pathogenic variants altering the Glutaminyl-tRNA synthetase 1 activity. We report a Tunisian child presenting with neonatal onset seizures, severe psychomotor delay, retinal abnormalities and MRI cerebral supratentorial atrophy lesions. Whole exome and Sanger sequencing revealed two new compound heterozygous variants of QARS1. Three-dimensional analysis of the mutant Glutaminyl-tRNA synthetase 1 predicted altered catalytic and tRNA-binding functions. Genotype-phenotype correlations emphasize the combined effect of the zygosity and the location of the pathogenic variants within the protein domains on the severity of the disease.
Predicted yield and soil organic carbon changes in grassland, arable, woodland, and agroforestry systems under climate change in a cool temperate Atlantic climate
Authors: Giannitsopoulos Michail L. , Burgess Paul J. , Graves Anil R. , Olave Rodrigo J. , Eden Jonathan M. , Herzog Felix
Published: July 2024

This study predicts the effects of climate change on crop yields, timber volumes and soil organic carbon in grassland, arable, ash woodland, poplar plantation, and silvopastoral and silvoarable systems in Northern Ireland. We modified a version of the biophysical Yield-SAFE agroforestry model that includes a RothC soil carbon module and also the effect of atmospheric CO2 fertilisation. The model was calibrated using existing field measurements and weather data from 1989 to 2021. The effect of two future climate scenarios were modelled, based on two representative concentration pathways (RCP 4.5 and RCP 8.5) for 2020–2060 and 2060–2100. The study revealed that the impact of future climate scenarios on grass and arable yields, and tree growth were positive with the effect of CO2 fertilisation more than offsetting a generally negative effect of increased temperatures and drought stress on yields. The predicted land equivalent ratio (LER) remained relatively constant between the baseline and the future climate scenarios for the silvopastoral system (1.08 to 1.11). The corresponding values for the silvoarable system were 0.87–0.92 based on arable and timber yields alone, or 1.11–1.17 if grass yields were included. In the silvopastoral system, but not the silvoarable system, the model suggested that climate change would benefit tree growth relative to the understorey crop. Greater losses of soil organic carbon were predicted under barley-only (1.02–1.18 t C ha− 1 yr− 1) than grassland (0.48–0.55 t C ha− 1 yr− 1), with relatively small differences between the baseline and climate scenarios. However, the analysis indicated that these losses could be mitigated by planting trees, but this effect was not immediate as soil organic matter would continue to decline for the first 10 years until the trees were well-established. The model was also used to examine the effect of different tree densities on the trade-offs between timber volume and understorey crop yields.
Time-optimal control of a solid-state spin amidst dynamical quantum wind
Authors: Sun Fang-Wen , Dong Yang , Jiang Wang , Liu Yong , Zhang Shao-Chun , Gao Xue-Dong , Yu Cui , Chen Xiang-Dong , Guo Guangcan , Moreira Ib´erio de P. R , Bofill Josep Maria , Sent´ıs Gael , Ramos Ramón , Albareda Guillermo
Published: July 2024

Time-optimal control holds promise across the full spectrum of quantum technologies, where the rapid generation of unitary gates and state transformations is crucial to mitigate decoherence effects. In practical scenarios, quantum systems are always immersed in an external time-dependent field or
potential, either owing to the inevitable influence of the environment or as a sought-after effect for
enhanced coherence. The challenge then lies in finding the time-optimal approach to navigate quantum
systems amidst dynamical ambient Hamiltonians, a pursuit that has proven elusive thus far. We showcase
the implementation of arbitrary quantum state transformations and a universal set of single-qubit gates
under a background Landau-Zener Hamiltonian. Leveraging the favorable coherence properties of timedomain Rabi oscillations, we achieve velocities surpassing the Mandelstam-Tamm quantum speed limit and significantly lower energy costs than those incurred by conventional quantum control techniques. These findings highlight a promising pathway to expedite and economize high-fidelity quantum operations.
The impact of COVID-19 pandemic on bloodstream infections in pediatrics and alteration in antimicrobial resistance phenotypes, 2020-2022
Authors: Fallah Fatemeh , Karimi Abdollah , Azimi Leila , Ghandchi Ghazale , Gholinejad Zari , Abdollahi Nafiseh , Oskooie Nazanin Ahari , Khodaei Hannan , Armin Shahnaz , Behzad Azita , Hashemi Seyedeh Masumeh , Ahmadizadeh Seyedeh Narjes , Alebouyeh Masoud
Published: July 2024

Background: Alteration in the etiology of bloodstream infection (BSI) and antimicrobial resistance (AMR) following the COVID-19 pandemic is not well known in children. This study aimed to investigate these changes during 2 years in Tehran, Iran.
Methods Children under 18 years old with suspected bacteremia/fungemia who had positive BACTEC blood cultures were included. Characterization of the isolates, antimicrobial susceptibility testing, and detection of multidrug-resistant (MDR) phenotypes were done based on standard protocols. Statistical analysis was done to measure the correlation of COVID-19 infection with BSI and AMR.
Results Out of 13,345 COVID-19 tests and 4,194 BACTEC blood culture requests, bacteremia/fungemia were confirmed in 10.34% of the patients who requested both tests simultaneously. The COVID-19 infection was confirmed in 25.3% of the patients with bacteremia/fungemia. The infection with Gram-negative bacteria, Gram-positive bacteria (GPB), and fungi was detected in 59.3%, 32.3%, and 8.31% of the cases, respectively. Pseudomonasspp. (21.3%), Klebsiella spp. (20.2%), CNS (15.8%), Acinetobacterspp. (9.6%), S. aureus (8%), and Enterococcus spp. (5%) were among the common isolates. In the case of BSI with GPB, a significant difference was measured among different hospital wards (p-value= 0.01). Moreover, a negative correlation was shown between the CNS bacteremia and COVID-19 infection (p-value= 0.029). Candida spp. and non-Candidayeasts were detected in 6.7% and 13.4% of the cases, respectively. Results of antibiotic susceptibility testing showed the highest frequency of resistance to azithromycin and oxacillin among CNS, azithromycin, tetracycline, and oxacillin among S. aureus, and tetracycline and trimethoprim/sulfamethoxazole among Enterococcus. Methicillin-resistance phenotype in the S. aureus (MRSA) and coagulase-negative Staphylococcusspp. (MR-CNS) was detected in 40% and 61.5% of the strains, respectively and the Enterococci were resistant to vancomycin in 33.3% of the isolates.
Conclusion A decline in the trend of BSI by GPB and an increase in AMR was shown in children during the COVID-19 pandemic. The rise in antibiotic resistance could be described by the overuse of antibiotics in COVID-19 patients, while the difference in types of medical interventions may explain the difference in the etiology of BSI among the hospital wards.
Transcriptome and Mendelian randomization were combined to screen and validate prognostic genes associated with lipid autophagy in oral squamous cell carcinoma
Authors: Chen Fangyu , Yan Qianqi , Guo Ya , zhang Jin , Li JianXue , Su LinHan
Published: July 2024

Background
Cancer cells can use fatty acids produced by lipophagy to continue growing and proliferating, but the regulation of lipophagy in oral squamous cell carcinoma (OSCC) remain poorly understood.
Methods
mRNA profiles, expression quantitative trait loci (eQTL) data, and ieu-b-4961 were scoured from the online databases. In TCGA-OSCC, the differentially expressed genes (DEGs) were screened between the tumors and paracancerous tissues. The weighted gene co-expression network analysis (WGCNA) was applied to obtain the key module genes highly related to lipophagy. Later, differentially expressed lipophagy-related genes (DE-LRGs) were determined by overlapping DEGs and key module genes. Next, the eQTL data of DE-LRGs was an exposure factor and the OSCC was an outcome factor in the two-sample Mendelian Randomization (MR). Meanwhile, sensitivity analyses and MR Steiger filtering were performed, and then candidate genes were selected to construct a prognostic risk model. Based on least absolute shrinkage and selection operator (LASSO)-Cox regression analyses, the prognostic genes were confirmed and a prognostic risk model was built. Afterwards, the tumors of OSCC patients were divided into high- and low-risk teams based on the median risk score. Finally, the immune microenvironment was evaluated using the estimate and single sample gene set enrichment analysis (ssGSEA) algorithms.
Results
A total of 271 DE-LRGs were determined by overlapping 4,712 DEGs and 308 key module genes. Among them, 18 exposure factors could affect directly OSCC as candidate genes. Next, 4 prognostic genes (CLTCL1, TNNC1, ALPK3, and PFKM) were identified, among them, CLTCL1 (odds ratio (OR) = 0.9997, 95% confidence intervals (CI) = 0.9995–0.9999, PIVW = 0.0020), PFKM (OR = 0.9997, 95% CI = 0.9995–0.9999, PIVW = 0.0067), and ALPK3 (OR = 0.9990, 95% CI = 0.9983–0.9997, PIVW = 0.0061) were protective factors and TNNC1 (OR = 1.0005, 95% CI = 1.0001–1.0008, PIVW = 0.0102) was a risk factor. A prognostic risk model was built, notably, the probability of overall survival (OS) in the low-risk team was higher than that in the high-risk team. Furthermore, we found that the low-risk team had higher immune, stromal, and ESTIMATE scores, and there were 23 differential immune cells between the two risk teams.
Conclusion
Generally, CLTCL1, PFKM, and ALPK3 were protective factors, while TNNC1 was a risk factor for OSCC patients. Our findings provided a new perspective on the treatment and prognosis of OSCC.
Verification of the effectiveness of combined platelet-rich plasma therapy and exercise therapy for patients with knee osteoarthritis up to one year post-treatment
Authors: Kawahara Tsuneo , Iida Shuhei , Isoda Kazuma , Kim Sungdo
Published: July 2024

Background Platelet-rich plasma (PRP) therapy is a promising treatment modality for knee osteoarthritis (OA). However, exercise therapy and activity of daily living (ADL) guidance are also recommended as core treatments in the Osteoarthritis Research Society International (OARSI) guidelines. However, there is limited research on the efficacy of combined PRP and exercise therapy. This study aimed to verify the effectiveness of this combined treatment. Methods The participants were patients diagnosed with knee OA and treated between January 2021 and December 2022. They were divided into three groups: 1) PRP + exercise therapy (PE group), 2) PRP therapy only (P group), and 3) exercise therapy only (E group). Outcomes were measured using the Knee Injury and Osteoarthritis Outcome Score (KOOS) and conducted before, 1 month, 3 months, and 1 year after treatment. Statistical analysis was performed using a one-way analysis of variance for within-group comparisons according to the time of each score. For those that showed a difference, the Bonferroni multiple comparison method was used to validate the results (p < 0.05). The treatment response rate was determined using the Outcome Measures in Rheumatology (OMERACT)-OARSI Responder criteria. Results There were no differences in pre-treatment KOOS between the three groups. In the PE group, pain, symptoms, and ADL improved after 1 month and continued to improve until 1 year. The P group showed improvement in pain after 1 month, but no significant changes were observed in the other items. In contrast, the E group showed improvement in each item from 3 months onwards, with all items remaining unchanged at 1 year. The PE group had a higher response rate than the other groups, with 50.0% at 1 month, 56.3% at 3 months, and 68.8% at 1 year, according to the responder criteria. Conclusions The combined treatment of PRP and exercise therapy demonstrated the synergistic advantages of both and proved to be most effective up to 1 year after treatment.
Anisotropic scattering in photothermal therapy and beyond: a detailed evaluation of transport approximation for gold nanoshells and nanospheres
Authors: Maurente André , Sousa Anderson
Published: July 2024

Photothermal therapy (PTT) utilizes thermal radiation to heat a targeted tissue for cancer treatment. Nanoparticles can be embedded in tissue regions to enhance radiation absorption, a practice known as plasmonic photothermal therapy (PPTT). This study focuses on computational simulations of heat transfer in PTT, particularly on the role of scattering phase functions of nanoparticles and the evaluation of the widely employed transport approximation. Mie phase functions of gold nanospheres and nanoshells are detailed taken into account in Monte Carlo simulations, and the heat equation is solved to provide the transient temperature distribution. Results are compared to those obtained using the transport approximation. Two transport approximation approaches are considered: the first approach disregards the asymmetry associated with the phase function of nanoparticles, as is common in PTT applications, while the second takes it into account. For nanoparticles within the 50 to 100 nm range, ideal for PPTT, results confirm the approximation is accurate. However, when the first approach led to inaccuracies, these were significantly reduced by the second. The study also investigated the impacts of size variability, resulting from imperfect synthesis processes of nanoparticles, on the phase function. This variability was effectively managed by the second approach. Overall, with the aid of the second approach, the findings demonstrate that transport approximation can accurately simulate PPTT and suggest considerable accuracy for imaging applications, significantly simplifying modeling.
Targeting Host Metabolic Niche to Kill Malaria Parasites
Authors: Jiang Rays , Siddiqui Faiza , Adapa Swamy , Cui Liwang
Published: July 2024

Malaria remains a global health challenge, exacerbated by artemisinin resistance. Inspired by our recent study targeting aberrant cancer heme metabolism, we propose a novel "bait-and-kill" strategy, focusing on the unique metabolic vulnerability of infected Red Blood Cells (iRBCs) to destroy host niche. We exploit three key factors: 1) mature RBCs inherently possess a truncated heme biosynthesis pathway capable of accumulating heme intermediates, i.e., porphyrins, 2) Uninfected RBCs exhibit impermeability to the heme precursor ALA (Aminolaevulinic acid), while infected RBCs demonstrate increased permeability, and 3) heme/porphyrin mediated activation of artemisinin has been established as the primary mechanism of action for their antimalarial activity. Utilizing the heightened membrane permeability of iRBCs, we employ the heme precursor ALA as “bait”, inducing heme intermediates accumulation. This synergizes with artemisinin, acting as the 'kill' agent, to effectively eradicate parasites. Uninfected RBCs do not uptake ALA, avoiding collateral damage. We present experimental characterization of drug-drug synergy in a malaria liver stage host cell line and successful elimination of artemisinin-resistant parasites during the blood stage, particularly parasites from the Great Mekong sub-region, a hotspot for antimalarial drug resistance. Leveraging safe drugs like ALA and artemisinin, tested globally, this synergistic strategy holds promise for large-scale deployment in malaria control.
RECOVR REALITY - Recover after injury or surgery to the brain and spinal cord with virtual Reality: IDEAL Stage 2a Clinical Feasibility Study
Authors: Bolton William Stephen , Sinha Rohitashwa , Cooper Sara , Adebola Oluwaseyi , Stephenson Elisa , Ewan Seonaid , Hunsley Rachel , Kearton Victoria , Stevens David , Mathew Ryan Koshi
Published: July 2024

Aim
Neurorehabilitation is fundamental to improve outcomes for patients recovering from injury to the central nervous system. Access to neurorehabilitation is limited by resource shortages; the consequences of which are unfulfilled therapy needs, longer hospital stays and detrimental effects on quality of life. Virtual reality (VR) could be used to enhance neurorehabilitation in a self-directed, safe, virtual environment. The aim of this study is to investigate the feasibility of a VR rehabilitation programme in an acute neurosurgical inpatient environment to improve neurorehabilitation.
Method
A single-group, prospective, clinical feasibility study was conducted in a tertiary UK neurosurgical department. The study included patients aged 16 and over who had neurosurgical care following surgery or traumatic brain or spinal cord injury. Participants were offered a VR session at least once per day for the first 14 days post-surgery/injury or until discharge, whichever came first, with reasons for non-engagement collected. Primary outcomes were feasibility outcomes and secondary outcomes included rehabilitation engagement.
Results
Of the thirty-nine eligible participants approached, thirty-two participants were recruited and received VR at least once. Intervention fidelity was deemed a success, as none of the VR equipment or applications failed. Median time between injury or surgery and first VR use was three days (IQR = 8.25). The Hopkins Rehabilitation Engagement scale and Simulation Sickness Questionnaires were deemed feasible instruments to measure outcomes.
Conclusions
We confirmed feasibility of using a VR rehabilitation tool for neurosurgical patients in this study. This now facilitates progression to a multi-centre, prospective, randomised, controlled, unblinded, parallel-group trial of VR-enhanced neurorehabilitation versus standard neurorehabilitation for improving recovery after neurotrauma or neurosurgery.
Current Knowledge and Practice of Pregnant Women Towards Gestational Hypertension: A Cross-Sectional Study of Nsukka Women
Authors: Dim Obinna Felix , Azubuike Ekwuofu , ONYEOJI OGECHI , Omeye Cynthia , Ukwe Chinwe
Published: July 2024

Background
Gestational hypertension is a major cause of maternal and perinatal mortality. Knowledge plays an essential role in decreasing the risk or threat of diseases; hence, this study aimed to assess the knowledge and practices of pregnant women toward gestational hypertension (GH) in Nsukka, Nigeria.
Methods
A descriptive, cross-sectional survey was conducted among 266 eligible pregnant women in two randomly selected hospitals in Nsukka using a well-structured and validated questionnaire. The questionnaire was self-administered. The data collected from the questionnaire were coded and analyzed using IBM SPSS version 27. Descriptive statistics such as frequencies and percentages were used to summarize the findings, while inferential statistics such as correlations and chi-square tests were used to determine the relationships between variables. For all the statistical analyses, p values < 0.05 were considered to indicate statistical significance.
Results
Of the 266 expectant mothers who participated in the study, 170 (63.9%) were aged 20 to 30 years. More than half of the participants (150, 56.4%) had a tertiary degree. The majority of the participants, 250 (94%), were married, and approximately half, 127 (47.7%), were in the third trimester. Only a handful of the participants (19%) were aware of GH. More than half of the participants, 161 (60.5%), strongly felt that gestational hypertension was preventable, and the majority, 180 (67.7%), preferred to visit the hospital if any unusual signs or symptoms were observed. Participants demonstrated low practice levels (20.28 ± 3.19). The level of education was the only sociodemographic component that was linked with mothers' practices toward GH (5.26(2)) (P = 0.04). The higher the mothers’ education level was, the better the mothers’ practices toward GH were.
Conclusion
The majority of participants had poor understanding and practice with GH. Only education level had an effect on pregnant women's attitudes toward GH.
Notoginsenoside R1, a novel natural PPARγ agonist, attenuates cognitive deficits in a mouse model of diabetic Alzheimer’s disease through enhancing GLUT4-dependent neuronal glucose uptake
Authors: Li Zongyang , Cui Ping , Su Rui , Yang Jihu , Chen Lei , Chen Fanfan , Pan Hua , Ma Guoxu , Zhang Yuan , Meng Xiangbao , Huang Guodong
Published: July 2024

Our previous studies demonstrated the potential of Notoginsenoside R1 (NGR1), a primary bioactive compound from Panax notoginseng, in alleviating diabetic encephalopathy in db/db mice and mitigating amyloid-β (Aβ)-induced neuronal damage. However, the impact of NGR1 on cognitive dysfunction in a diabetic Alzheimer’s disease (AD) mouse model remains unclear. In this investigation, we identified NGR1 as a novel PPARγ agonist through a dual-luciferase reporter assay system. NGR1 treatment significantly promoted the membrane translocation of GLUT4 and enhanced 2-deoxyglucose uptake in primary mouse hippocampal neurons. Furthermore, intragastric administration of NGR1 (40 mg/kg/day) for 16 weeks notably mitigated cognitive deficits in APP/PS1xdb/db mice. This treatment correlated with reduced blood glucose levels, lowered serum HbA1c, and decreased serum insulin levels, coupled with enhanced glucose tolerance and insulin sensitivity. Additionally, NGR1 treatment ameliorated Aβ burden, suppressed microglia-induced neuroinflammation, and notably increased cerebral glucose uptake, as demonstrated by 18F-FDG PET scans. NGR1 treatment could upregulate PPARγ and GLUT4 expression and increase phosphorylation of Akt at Ser473 while decreasing phosphorylation of IRS-1 at Ser616 in the hippocampus of APP/PS1xdb/db mice. Crucially, the protective effects of NGR1 were abolished by co-administration with a selective PPARγ inhibitor GW9662. In conclusion, NGR1 demonstrated efficacy in enhancing neuronal glucose uptake through the activation of the PPARγ/Akt/GLUT4 signaling pathways in APP/PS1xdb/db mice, positioning it as a promising candidate for diabetic AD treatment.
Human-Simulated Intelligent Control of Torsional Vibration in Magneto-rheological Variable Stiffness-Damping-Moment of Inertia Transmission System based on Hybrid Taguchi Genetic Algorithm
Authors: Li Wenfeng , Liu Le , Ge Xinfeng , Liang Manying , Deng Xiong , Gao Jianrong
Published: July 2024

In addressing the distinct influence mechanisms of torsional stiffness, torsional damping, and moment of inertia on the torsional vibration behavior of transmission systems, a human-simulated intelligent control strategy based on hybrid Taguchi genetic algorithm is proposed for the torsional vibration of magneto-rheological (MR) transmission system with variable stiffness, variable damping and variable inertia. Initially, the research conducts an in-depth analysis of the effects exerted by torsional stiffness, torsional damping, and moment of inertia on the transmission system dynamics. Subsequently, a comprehensive dynamics model for the MR transmission system with adaptable stiffness, damping, and inertia parameters is formulated, grounded on the conceptualization of an MR torsional vibration absorber. Drawing from the dynamic optimization outcomes facilitated by the hybrid Taguchi genetic algorithm, control parameters governing torsional stiffness, torsional damping, and moment of inertia are refined. This refinement process underpins the design of a human-simulated intelligent controller distinguished by its partitioned and multimodal characteristics. Notably, this controller framework is crafted to accommodate considerations across both temporal and spectral domains. Following the controller's design phase, rigorous simulation analyses are conducted to assess its efficacy. Results substantiate that the human-simulated intelligent control mechanism, underpinned by the hybrid Taguchi genetic algorithm, proficiently attenuates torsional vibrations across a broad spectrum of frequency bands. Furthermore, it is observed to markedly enhance the overall output characteristics of the MR transmission system.
Identification of the ceRNA axis of circ_0000006/miR-483-5p/KDM2B in the progression of aortic aneurysm to aorta dissection
Authors: Liu Yong , Tan Xiong , Wang Liang , Jin Weitao , He Yangchen , yan Yu , Hu Kai , Wang Hao , Xiang Chaohu , Hou Ming , Lai Yinglong
Published: July 2024

Background
Aortic aneurysm (AA) and aortic dissection (AD) are serious cardiovascular disorders with a high risk of mortality. The molecular mechanisms underlying the progression from AA to AD are not well understood. This study aimed to identify the key circular RNA (circRNA)-microRNA (miRNA)-messenger RNA (mRNA) regulatory axis involved in this disease progression.
Methods
CircRNA microarray, miRNA microarray, and mRNA sequencing were performed on plasma samples from healthy controls, AA patients, and AD patients. Bioinformatics analysis integrated the expression profiles to identify dysregulated circRNA-miRNA-mRNA networks. Key molecules were validated in vascular smooth muscle cells (VSMCs) and an AD mouse model. Cell proliferation, migration, and phenotypic transition assays were conducted after modulating the identified circRNA. The impact on AD progression was evaluated in mice upon circRNA knockdown.
Results
A total of 12 circRNAs were found upregulated in AD compared to AA samples. miR-483-5p was downregulated while its targets KDM2B and circ_0000006 were upregulated in AD. Silencing circ_0000006 in VSMCs inhibited PDGF-induced phenotypic switching, proliferation, and migration by increasing miR-483-5p and decreasing KDM2B levels. In the AD mouse model, knockdown of circ_0000006 alleviated disease progression with similar molecular changes.
Conclusion
The study identified a novel circ_0000006/miR-483-5p/KDM2B axis dysregulated during AD progression. Targeting this axis, especially circ_0000006, could be a potential strategy to mitigate the transition from AA to AD by modulating VSMC phenotype and function.
Molecular mechanisms of the Xiao-chai-hu-tang on chronic stress-induced colorectal cancer growth based on an integrated network pharmacology and RNA sequencing approach with experimental validation
Authors: Yao Wang , Hua Dong-Ming , Zhang Ying-Ru , Zhao Yi-Yang , Feng Ying , Zhang Zhao-Zhou , Ni Zhong-Ya , Guo Hai-dong , Guan Yun-Feng , Wang Yan
Published: July 2024

Background
Chronic stress is a risk factor for the development of colorectal cancer (CRC). Xiao-Chai-Hu-Tang (XCHT) is a traditional Chinese medicine prescription and has been widely used to treat chronic stress-related diseases and cancer. However, its role in chronic stress-induced CRC remains unclear.
Methods
Our study aimed to investigate the roles of XCHT in CRC development under chronic stress. A xenografted CRC mouse model exposure to chronic restraint stress (CRS) was used to determine the effects of XCHT on CRC growth in vitro and in vivo. XCHT (10.27, 20.54 g/kg) were given by oral gavage once a day. RNA-sequencing was combined with network pharmacology to investigate potential target and pathway in this study. ELISA, RT-qPCR and immunofluorescence were performed to detect the expression of inflammation related genes. Glycolysis related genes and phenotype were evaluated by WB, RT-qPCR and seahorse.
Results
XCHT significantly inhibited CRC growth under chronic stress in a dose-dependent manner. Mechanistically, XCHT suppressed the expression levels of glycolysis associated enzymes and inflammatory factors caused by chronic stress. Moreover, XCHT significantly mitigated the activity of the JAK2/STAT3 signaling which was activated by chronic stress induced IL-6.
Conclusions
XCHT could reverse the tumor energy metabolism reprogramming and improve the inflammatory microenvironment in CRC under chronic stress through the IL-6/JAK2/STAT3 pathway. Therefore, XCHT might represent a promising therapeutic strategy for suppressing psychologically associated CRC progression.
Trending Preclinical Medical Student Confidence, the Impact of Gender, and Associated Performance: A Single Institution Study
Authors: Stolfi Adrienne , Clark Carson , Benintendi Isabella , Westrick Alexis , Whitehead Katie , Silva Annelise
Published: July 2024

Introduction: The relationship between confidence and competence in medical students may vary with experience and the situation, but ultimately this relationship will greatly affect patient care and outcomes.
Methods: De-identified self-reported confidence polling data, gender, Medical College Admission Test (MCAT) percentiles, and National Board of Medical Examiners (NBME) exam scores for two course modules (‘Origins’ and ‘Staying Alive’) were analyzed for 117 medical students. Confidence in mastery of course material was rated on a 3-point Likert scale at the beginning and end of each graded session throughout the courses. Associations were analyzed with Mann-Whitney U tests, Wilcoxin signed ranks tests, Spearman rank correlation coefficients, and multiple linear regressions.
Results: Confidence from the beginning to the end of the Origins module dropped significantly for all students. Males demonstrated a decreasing trend in confidence scores throughout the Staying Alive module. Post-session confidence was significantly higher than pre-session confidence in both modules, for all students combined as well as separately for females and males. MCAT percentile was the only significant predictor of NBME exam scores for both modules.
Discussion:There are several considerations for the demonstrated decreasing confidence throughout learning modules, including student burnout. The male-predominant decline in confidence raises interesting questions about gender and resilience, and may reflect unique female experiences in medicine which advance self-confidence. Finally, the lack of correlation between self-assessed confidence and objective performance is interesting, which could be attributed to the Dunning-Kruger effect.
Prognostic and Clinical Heterogeneity of PD1 and PD-L1- Immunohistochemical Scores in Endometrial Cancers
Authors: Proppe Louisa , Jagomast Tobias , Beume Sophie , Köster Frank , Bräutigam Karen , Rody Achim , Perner Sven , Hemptenmacher Franziska , Ribbat-Idel Julika , Hanker Lars Christian
Published: July 2024

Introduction: PD1/PD-L1 inhibition (ICi) has recently become a new standard of care for patients with advanced MMR-deficient (MMRd) endometrial cancers. Nevertheless, response to immunotherapy is more complex than the presence of a single biomarker and therefore it remains challenging to predict patients response to ICi beyond MMRd tumors. Elevated PD-L1 expression (CPS ≥ 1) is often used as a prognostic marker as well as a predictive biomarker of response to ICi in different tumor types. In a retrospective, patient derived study, we analyzed PD1- and PD-L1 staining and correlated the results of different scores to clinical data to evaluate the prognostic impact of these scores.
Materials and Methods: Immunohistochemical analysis of the receptor PD1 and the receptor ligand PD-L1 were performed on TMAs of primary paraffin‑embedded tumor samples. All patients were treated for primary endometrial cancer in the Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Campus-Lübeck, Germany between the years 2006–2018.. The evaluation and determination of the tumor proportion scoring (TPS), the combined positive score (CPS) and the immune cell scoring (IC) was automatically assessed semi-quantitatively, and results were correlated with clinicopathological characteristics and survival.
Results: 130 samples were evaluable and 64% showed a positivity (IC > 0) for the receptor PD1 and 56% for the receptor ligand PD-L1. Patients with a PD1 IC Score ≥ 1 showed a significant longer disease-free survival of 140 months (95% confidence interval (CI): 124–158) compared to patients with a lower IC < 1 for PD1 of 89 months (95% confidence interval (CI): 69–110); p = 0.017). Furthermore, the disease-free survival for patients with a CPS ≥ 5 for PD1 was longer (153.7 months (95% confidence interval (CI): 134–173.6) vs. 98.6 months (95% confidence interval (CI): 83–114); p = 0.036). Additionally, a PD1 CPS ≥ 5 showed a better overall survival but the result was not statistically significant. No difference in survival was found between patients with PD-L1 higher or lower than CPS 5.
Conclusion: In this study we pointed out that there are significant clinical differences among several immunohistochemical scoring systems. In our trial, a PD1-positivity with CPS ≥ 5 and IC ≥ 1 were significantly associated to a better disease-free survival while there was no association with TPS. The PD1-IC scoring was associated with MMRd while the TPS scoring was not. Therefore, PD1-IC could be more appropriate for endometrial carcinomas compared to TPS and could also add prognostic information beside the more established PD-L1-staining. Further prospective studies are needed for a validation of these scores in combination with other biomarkers.
Green synthesis of fluorescent N-doped carbon quantum dots from castor seeds and their applications in cell imaging and pH sensing
Authors: Elkun Salah , Ghali Mohsen , Sharshar Taher , Mosaad Mohsen Mohamed
Published: July 2024

Water-soluble fluorescent N-doped carbon quantum dots (N-CQDs) were hydrothermally prepared through a green synthesis route using castor seeds as a single precursor and a hydrothermal method. Several experimental techniques have been used to characterize synthesized N-CQDs to confirm their structure and to verify their applicability in cell imaging and pH sensing. The synthesized N-CQDs were found to have are characterized by amorphous nature with a spherical shape with an average particle size of 6.57 nm as revealed from XRD and TEM measurements. The FTIR results reveal the presence of carboxylic and hydroxyl functional groups on the surface of the CQDs, which was also confirmed by XPS analysis. The fluorescence characterization of the synthesized N-CQDs showed blue emission and excitation dependence. It was found that the optimal excitation and emission wavelengths were 360 and 432 nm, respectively. Moreover, the fluorescence intensity of N-CQDs showed good linear dependence with the pH values in ranges of 3.5 − 7.5 sand 8 − 12 as well as high sensitivity for slight changes of pH values. According to these results, two fluorescent pH sensors were created based on acidic and basic media. The obtained N-CQDs have zeta potential of -21.86 mV and thus have excellent stability in water. Moreover, N-CQDs derived from the castor seeds have antimicrobial activity and exhibits low cytotoxicity to WI-13 cells with IC50 = 394.4 ± 13.8 µg/mL. The results of this study demonstrated that the synthesized N-CQDs derived from castor seeds can be used as pH sensing and antimicrobial materials. On the other hand, they are also promising in applications in cell imaging, thermo-sensing and optoelectronics.