bluuebunny/crossref_metadata_2025 huggingface dataset:
Nietzsche, the Muslim Falāsifa, and Leo Strauss's Avicennan Turn
Authors: Mufti Malik
Published: January 2024

Impressed by Friedrich Nietzsche's critique of liberalism but alarmed by its consequences, Leo Strauss turned in the 1930s to the medieval Islamic philosophers (falāsifa). A review of a key cleavage in their political philosophy—reflected in the contrasting positions of Ibn Rushd and Ibn Sina—identifies the fundamental alternatives Strauss found available to him on the role of religion in politics, and on the necessity and efficacy of political activism more generally. It thus illuminates the trajectory of Strauss's thoughts on the relationship between reason and revelation: from an initial appreciation for the “golden mean” between Nietzsche and liberalism he believed he had found in the writings of al-Farabi and Ibn Rushd, to a more apolitical “Avicennan” stance after his arrival in America. This last, it is suggested, was a contingent stance requiring reconsideration in light of new circumstances in American politics today.
‘Self-reliance first, children's care-giving second’: older adults' experience and conceptualisation of ageing-in-place in rural China
Authors: Chen Lin , Mao Xupeng , Kahana Eva , Zhao Wenlu
Published: January 2024

Ageing-in-place has become an internationally favoured policy and practice response to population ageing. However, limited literature has sought to understand this concept from Chinese older adults' perspectives, especially in rural China. The purpose of this study is to explore how older adults in rural China conceptualise ageing-in-place. This study took a qualitative approach by carrying out in-depth interviews with snowball-sampled older adults from a rural village in Shandong Province, China (N = 30). Participants conceptualised their ageing-in-place as consisting of two phases: first, when they felt self-reliant, these older adults preferred to live independently in the village; and second, when their capability declined, they would expect care-giving from their children. Autonomy was essential to participants' decision to age in place. The village offered both a physical and social environment in which participants could sustain their self-identity. This decision to age in place independently also related to participants' proactive adaptation to their children's evolving practices of filial piety. Still, had their capabilities declined, they reported they would expect their children's care-giving and move in with their children. Our findings suggest that older adults in rural China conceptualise ageing-in-place as a dynamic process that evolves as they age and experience changes in their needs and capabilities. This perception expands critical notions of ageing-in-place by highlighting rural older adults' flexible conceptualisation of the ‘place’ in which they plan to age. This study sheds light on socioculturally nuanced understandings of ageing-in-place while providing evidence to inform tailored policy and practice development in rural China.
Using automated text classification to explore uncertainty in NICE appraisals for drugs for rare diseases
Authors: Wiedmann Lea , Blumenau Jack , Carroll Orlagh , Cairns John
Published: January 2024

Objective

This study examined the application, feasibility, and validity of supervised learning models for text classification in appraisals for rare disease treatments (RDTs) in relation to uncertainty, and analyzed differences between appraisals based on the classification results.

Methods

We analyzed appraisals for RDTs (n = 94) published by the National Institute for Health and Care Excellence (NICE) between January 2011 and May 2023. We used Naïve Bayes, Lasso, and Support Vector Machine models in a binary text classification task (classifying paragraphs as either referencing uncertainty in the evidence base or not). To illustrate the results, we tested hypotheses in relation to the appraisal guidance, advanced therapy medicinal product (ATMP) status, disease area, and age group.

Results

The best performing (Lasso) model achieved 83.6 percent classification accuracy (sensitivity = 74.4 percent, specificity = 92.6 percent). Paragraphs classified as referencing uncertainty were significantly more likely to arise in highly specialized technology (HST) appraisals compared to appraisals from the technology appraisal (TA) guidance (adjusted odds ratio = 1.44, 95 percent CI 1.09, 1.90,p = 0.004). There was no significant association between paragraphs classified as referencing uncertainty and appraisals for ATMPs, non-oncology RDTs, and RDTs indicated for children only or adults and children. These results were robust to the threshold value used for classifying paragraphs but were sensitive to the choice of classification model.

Conclusion

Using supervised learning models for text classification in NICE appraisals for RDTs is feasible, but the results of downstream analyses may be sensitive to the choice of classification model.
Economic hardship and adolescent behavioral outcomes: Within- and between-family associations
Authors: Miller Portia , Blatt Lorraine , Hunter-Rue Daniesha , Barry Kelly R. , Jamal-Orozco Nabila , Hanson Jamie L. , Votruba-Drzal Elizabeth
Published: January 2024

Understanding how youth perceive household economic hardship and how it relates to their behavior is vital given associations between hardship and behavioral development. Yet, most studies ignore youth’s own perceptions of economic hardship, instead relying solely on caregiver reports. Moreover, the literature has tended to treat economic hardship as a stable force over time, rather than a volatile one that varies month-to-month. This study addressed extant limitations by collecting monthly measures of economic hardship, specifically caregiver- and youth-reported material deprivation and youth-reported financial stress, and youth internalizing and externalizing problems from 104 youth–caregiver dyads (youth: 14–16 years, 55% female, 37% Black, 43% White) over nine months. We examined month-to-month variability of these constructs and how youth-reports of material deprivation and financial stress predicted their behavior problems, controlling for caregiver-reports of material deprivation. We found that hardship measures varied month-to-month (ICCs = 0.69–0.73), and youth-reported material deprivation positively predicted internalizing when examining both within- and between-individual variability (β = .19–.47). Youth-reported financial stress positively predicted within-individual variation in externalizing (β = .18), while youth reports of material deprivation predicted externalizing when looking between families (β = .41). Caregiver-reported material deprivation was unrelated to youth behavior when accounting for youth perceptions of economic hardship.
Nursing students satisfaction and self-confidence with standardized patient palliative care simulation focusing on difficult conversations
Authors: Gillan Pauline Catherine , Johnston Sandra
Published: January 2024

Objectives

Lack of experience communicating with patients and families at the end of life are key concerns for nursing students. Palliative care simulation using standardized patients (SPs) focusing on difficult conversations may lead to increased self-confidence in providing palliative and end-of-life care in clinical practice. There is currently a paucity of research on SP palliative care simulations in undergraduate nursing education. The objective of this research was to assess 3rd year undergraduate nursing students’ levels of satisfaction and self-confidence with palliative and end-of-life care simulations focusing on difficult conversations, as measured by the Student Satisfaction and Self-Confidence in Learning Scale (SSSCLS) and the Simulation Design Scale (SDS).

Methods

A descriptive post-intervention study. Four palliative care simulation days, consisting of 2 clinical scenarios, were conducted over 4 weeks. The first simulation was an outpatient palliative care clinic scenario, and the second was an inpatient hospital scenario. Nursing students enrolled in a 3rd year nursing palliative care elective (n = 51) at an Australian university were invited to participate. Students who attended simulation days were eligible to participate (n = 31). Immediately post-simulation, students were invited to complete the SSSCLS and the SDS. Fifty-seven surveys were completed (simulation 1, n = 28; simulation 2, n = 29). The data were analyzed using descriptive statistics.

Results

Results showed that students had high levels of self-confidence in developing palliative care and communication skills after both simulation experiences and high levels of satisfaction with the SP simulations.

Significance of results

The lack of published literature on palliative care and end-of-life SP simulation highlights the need to collect further evidence to support this as an innovative approach to teaching palliative care. SP palliative care simulation focusing on difficult conversations assists in developing students’ communication skills and improves satisfaction and self-confidence with palliative and end-of-life care.
A New Protocol to Study Mind-Wandering for Air Traffic	Controllers
Authors: Servais Anaïs , Riedinger Florine , Granger Géraud , Imbert Jean-Paul , Barbeau Emmanuel J. , Hurter Christophe
Published: January 2024

Abstract: Although mind-wandering decreases processing of external information, it remains understudied in air traffic controllers (ATCOs), who must constantly attend to external information. Using autobiographical memory retrieval, we propose an innovative protocol to mimic the moment when ATCOs start mind-wandering. A total of 16 participants performed an ATCO simulation task while we triggered attentional switches toward their inner world using memory probes and recorded eye movements with eye-tracking glasses and a camcorder. We successfully induced one to five spontaneous memories for half of the participants and showed the impact on response times ( Mdn = +0.74 s) to clear flight level. Preliminary results suggest that autobiographical memory could be used to identify a temporal ocular marker – particularly gaze aversion, also positively related to self-reported mind-wandering – to detect the attentional switch.
Does Deliberately Going Beyond Alarms in Stall Recovery Exercises	Lead to Negative Training?
Authors: Landman Annemarie , Mol Douwe , van Emmerik Martijn , Groen Eric
Published: January 2024

Abstract: We investigated whether deliberately going beyond alarms during aerodynamic stall recovery exercises may result in negative training. Two groups of 20 airline pilots received stall recovery training in a moving-base simulator. The “delayed-response” group induced the stall themselves. The “immediate-response” group was presented with paused situations and had to recover immediately after unpausing. In a surprising transfer test, the pilots in the delayed-response group showed less aggressive unloading, and experienced significantly more time pressure compared to the pilots in the immediate-response group. In a stall cue recognition test, the delayed-response group performed nearly significantly better. We conclude that experiencing the progression of an aerodynamic stall during training has positive effects on pilot performance, even if this requires unprocedural behavior.
Evaluation of the Exospheric Temperature Modeling From Different Empirical Orthogonal Functions
Authors: Yang Xu , Weng Libin , Lei Jiuhou , Zhu Xiaoqian , Ruan Haibing , Ren Dexin , Li Zhongli , Li Ruoxi , Chen Liangjie
Published: January 2024

In this paper, we constructed the Exospheric Temperature Models (ETM) on the basis of CHAMP and GRACE data using different empirical orthogonal functions (EOFs). The EOFs of the exospheric temperature can be derived either from satellite data directly or from the outputs of the Thermosphere Ionosphere Electrodynamics General Circulation Model (TIEGCM) and MSIS models by applying the Principal Component Analysis method. Then, the thermospheric mass densities calculated from ETM are used to compare with the observed data in order to evaluate the performance of different ETM models. It was found that all these three models can provide good specification of thermospheric density including day‐night, seasonal, and latitudinal variations. However, the ETM based on CHAMP and GRACE data gives a better performance in modeling the Equatorial Thermospheric Anomaly and the Midnight Density Maximum features than the MSIS‐ETM and TIEGCM‐ETM. Specifically, independent SWARM‐C data comparison showed that the Relative Deviations and corresponding Root‐Mean‐Square‐Errors of our Texo models are less than 8.9% and 22.8%, much better than the MSIS‐00 model.
Hyporheic Flows in Stratified Sediments: Implications on Residence Time Distributions
Authors: Marzadri Alessandra , Ciriello Valentina , de Barros Felipe P. J.
Published: January 2024

The fate of nutrients and contaminants in fluvial ecosystems is strongly affected by the mixing dynamics between surface water and groundwater within the hyporheic zone, depending on the combination of the sediment's hydraulic heterogeneity and dune morphology. This study examines the effects of hydraulic conductivity stratification on steady‐state, two‐dimensional, hyporheic flows and solute residence time distribution. First, we derive an integral transform‐based semi‐analytical solution for the flow field, capable of accounting for the effects of any functional shape of the vertically varying hydraulic conductivity. The solution considers the uneven distribution of pressure at the water‐sediment interface (i.e., the pumping process) dictated by the presence of dune morphology. We then simulate solute transport using particle tracking. Our modeling framework is validated against numerical and tracer data from flume experiments and used to explore the implication of hydraulic conductivity stratification on the statistics and pdf of the residence time. Finally, reduced‐order models are used to enlighten the dependence of key residence time statistics on the parameters characterizing the hydraulic conductivity stratification.
Sandy Fingerprints Trace Supply Sources
Authors: Herring Molly
Published: January 2024

Geological forensics can trace raw materials back to their source. As global sand demand increases, a new tool could help identify illegal and informal sand mining.
Modulation of learning safety signals by acute stress: paraventricular thalamus and prefrontal inhibition
Authors: Wang Zongliang , Wang Zeyi , Zhou Qiang
Published: January 2024

Distinguishing between cues predicting safety and danger is crucial for survival. Impaired learning of safety cues is a central characteristic of anxiety-related disorders. Despite recent advances in dissecting the neural circuitry underlying the formation and extinction of conditioned fear, the neuronal basis mediating safety learning remains elusive. Here, we showed that safety learning reduces the responses of paraventricular thalamus (PVT) neurons to safety cues, while activation of these neurons controls both the formation and expression of safety memory. Additionally, the PVT preferentially activates prefrontal cortex somatostatin interneurons (SOM-INs), which subsequently inhibit parvalbumin interneurons (PV-INs) to modulate safety memory. Importantly, we demonstrate that acute stress impairs the expression of safety learning, and this impairment can be mitigated when the PVT is inhibited, indicating PVT mediates the stress effect. Altogether, our findings provide insights into the mechanism by which acute stress modulates safety learning.
MUC1-C is a target of salinomycin in inducing ferroptosis of cancer stem cells
Authors: Daimon Tatsuaki , Bhattacharya Atrayee , Wang Keyi , Haratake Naoki , Nakashoji Ayako , Ozawa Hiroki , Morimoto Yoshihiro , Yamashita Nami , Kosaka Takeo , Oya Mototsugu , Kufe Donald W.
Published: January 2024

The oncogenic MUC1-C transmembrane protein is a critical effector of the cancer stem cell (CSC) state. Addiction to MUC1-C for self-renewal in the progression of human cancers has emphasized the need for development of anti-MUC1-C agents. However, there are presently no approved small molecules for targeting MUC1-C-dependent CSCs. In screening for small molecules, we identified salinomycin (SAL), an inducer of ferroptosis, as a potent inhibitor of MUC1-C signaling. We demonstrate that SAL suppresses MUC1-C expression by disrupting a NF-κB/MUC1-C auto-inductive circuit that is necessary for ferroptosis resistance. Our results show that SAL-induced MUC1-C suppression downregulates a MUC1-C→MYC pathway that activates genes encoding (i) glutathione-disulfide reductase (GSR), and (ii) the LDL receptor related protein 8 (LRP8), which inhibit ferroptosis by generating GSH and regulating selenium levels, respectively. GSR and LRP8 contribute to the function of glutathione peroxidase 4 (GPX4), an essential negative regulator of ferroptotic cell death. We demonstrate that targeting MUC1-C genetically or with the GO-203 peptide inhibitor suppresses GPX4 expression and GPX activity in association with the induction of ferroptosis. Studies of CSCs enriched by serial passage as tumorspheres further demonstrate that the effects of SAL are mediated by downregulation of MUC1-C and thereby overcoming resistance to ferroptosis. As confirmation of these results, rescue of MUC1-C downregulation with the MUC1-C cytoplasmic domain (i) reversed the suppression of GSR, LRP8 and GPX4 expression, and (ii) attenuated the induction of ferroptosis. These findings identify SAL as a unique small molecule inhibitor of MUC1-C signaling and demonstrate that MUC1-C is an important effector of resistance to ferroptosis.
Mammalian target of rapamycin inhibition protects glioma cells from temozolomide-induced cell death
Authors: Sauer Benedikt , Lorenz Nadja I. , Divé Iris , Klann Kevin , Luger Anna-Luisa , Urban Hans , Schröder Jan-Hendrik , Steinbach Joachim P. , Münch Christian , Ronellenfitsch Michael W.
Published: January 2024

Glioblastoma is an incurable brain tumor with a median survival below two years. Trials investigating targeted therapy with inhibitors of the kinase mTOR have produced ambiguous results. Especially combination of mTOR inhibition with standard temozolomide radiochemotherapy has resulted in reduced survival in a phase II clinical trial. To date, this phenomenon is only poorly understood. To recreate the therapeutic setting in vitro, we exposed glioblastoma cell lines to co-treatment with rapamycin and temozolomide and assessed cell viability, DNA damage and reactive oxygen species. Additionally, we employed a novel translatomic based mass spectrometry approach (“mePROD”) to analyze acute changes in translated proteins. mTOR inhibition with rapamycin protected glioblastoma cells from temozolomide toxicity. Following co-treatment of temozolomide with rapamycin, an increased translation of reactive oxygen species (ROS)-detoxifying proteins was detected by mass spectrometry. This was accompanied by improved ROS-homeostasis and reduced DNA damage. Additionally, rapamycin induced the expression of the DNA repair enzyme O-6-methylguanine-DNA methyltransferase (MGMT) in glioblastoma cells with an unmethylated MGMT gene promotor. Inhibition of mTOR antagonized the cytotoxic effects of temozolomide in vitro. The induction of antioxidant defences and MGMT are two underlying candidate mechanisms. Further functional experiments in vitro and in vivo are warranted to characterize this effect that appears relevant for combinatorial therapeutic strategies.
Mechanisms and effects of NLRP3 in digestive cancers
Authors: Si Yuxin , Liu Lei , Fan Zhe
Published: January 2024

Inflammasomes are thought to be important mediators of host defense against microbial pathogens and maintenance of gastrointestinal tract homeostasis. They can modulate caspase-1 to promote IL-18 and IL-1β secretion and promote phagocytosis induced by bacterial pathogens. NLRP3 is an inflammasome comprising a multiprotein complex assembled by pattern recognition receptors in the cell cytoplasm. It is a crucial component of the innate immune system. Dysregulation of NLRP3 may contribute to inflammatory diseases and intestinal cancers. Recent research suggests that NLRP3 plays an essential role in tumor development; therefore, intensive study of its mechanism is warranted as it could play a key role in the treatment of digestive system tumors. In this review, we discuss the mechanism and role of NLRP3 in tumors of the digestive system and response strategies to modulate NLRP3 for potential use in tumor treatment.
Chromosome-level assembly of Triplophysa yarkandensis genome based on the single molecule real-time sequencing
Authors: She Jiacheng , Chen Shengao , Liu Xuan , Huo Bin
Published: January 2024

Triplophysa yarkandensis, a species of freshwater fish endemic to Xinjiang, China, is currently classified as endangered. The objective of this study was to obtain the chromosome-level genome of T. yarkandensis using PacBio and Hi-C techniques. The PacBio sequencing technology resulted in an assembly of 520.64 Mb, with a contig N50 size of 1.30 Mb. Hi-C data was utilized for chromosome mapping, ultimately yielding 25 chromosome sequences. The success rate of chromosome mapping was 93%, with a scaffold N50 of 19.14 Mb, and a BUSCO evaluation integrity of 94.1%. The genome of T. yarkandensis encompasses 25,505 predicted protein-coding genes, with a total of 30,673 proteins predicted. The BUSCO evaluation integrity for predicted protein-coding genes was found to be 91.5%. Additionally, the genome contained a genomic repeat sequence accounting for 27.29% of its total length. Future research employing comparative genomics holds considerable importance in elucidating the molecular mechanisms behind saline-alkali adaptation and ensuring the conservation of biological resources.
Environmental and geographical factors influence the occurrence and abundance of the southern house mosquito, Culex quinquefasciatus, in Hawai‘i
Authors: Villena Oswaldo C. , McClure Katherine M. , Camp Richard J. , LaPointe Dennis A. , Atkinson Carter T. , Sofaer Helen R. , Berio Fortini Lucas
Published: January 2024

Hawaiian honeycreepers, a group of endemic Hawaiian forest birds, are being threatened by avian malaria, a non-native disease that is driving honeycreepers populations to extinction. Avian malaria is caused by the parasitePlasmodium relictum, which is transmitted by the invasive mosquitoCulex quinquefasciatus. Environmental and geographical factors play an important role in shaping mosquito-borne disease transmission dynamics through their influence on the distribution and abundance of mosquitoes. We assessed the effects of environmental (temperature, precipitation), geographic (site, elevation, distance to anthropogenic features), and trap type (CDC light trap, CDC gravid trap) factors on mosquito occurrence and abundance. Occurrence was analyzed using classification and regression tree models (CART) and generalized linear models (GLM); abundance (count data) was analyzed using generalized linear mixed models (GLMMs). Models predicted highest mosquito occurrence at mid-elevation sites and between July and November. Occurrence increased with temperature and precipitation up to 580 mm. For abundance, the best model was a zero-inflated negative-binomial model that indicated higher abundance of mosquitoes at mid-elevation sites and peak abundance between August and October. Estimation of occurrence and abundance as well as understanding the factors that influence them are key for mosquito control, which may reduce the risk of forest bird extinction.
Non-linear QED approach for betatron radiation in a laser wakefield accelerator
Authors: Ong J. F. , Berceanu A. C. , Grigoriadis A. , Andrianaki G. , Dimitriou V. , Tatarakis M. , Papadogiannis N. A. , Benis E. P.
Published: January 2024

Laser plasma-based accelerators provide an excellent source of collimated, bright, and adequately coherent betatron-type x-ray pulses with potential applications in science and industry. So far the laser plasma-based betatron radiation has been described within the concept of classical Liénard–Wiechert potentials incorporated in particle-in-cell simulations, a computing power-demanding approach, especially for the case of multi-petawatt lasers. In this work, we describe the laser plasma-based generation of betatron radiation at the most fundamental level of quantum mechanics. In our approach, photon emission from the relativistic electrons in the plasma bubble is described within a nonlinear quantum electrodynamics (QED) framework. The reported QED-based betatron radiation results are in excellent agreement with similar results using Liénard–Wiechert potentials, as well as in very good agreement with betatron radiation measurements, obtained with multi-10-TW lasers interacting with He and multielectron N$$_2$$

2

gas targets. Furthermore, our QED approach results in a dramatic reduction of the computational runtime demands, making it a favorable tool for designing betatron radiation experiments, especially in multi-petawatt laser facilities.
Synthesis and characterization of a new copper-based polyoxomolybdate and its catalytic activity for azide-alkyne cycloaddition reaction under UV light irradiation
Authors: Amini Mojtaba , Yousofvand Asmaa , Hosseinifard Mojtaba , Bayrami Arshad , Janczak Jan
Published: January 2024

A new organic-functionalized Cu-based Anderson-type polyoxomolybdate, namely (C7H15N4)2[Na(H2O)4]2[C6H12CuMo6N2O24]·2(H2O) (CuII-POM), was synthesized via a simple one-pot reaction and subsequently characterized using a range of analytical and spectral techniques. Structural investigation by single crystal X-ray diffraction analysis revealed that the polyanion component of the synthesized compound (i.e. [C6H12CuMo6N2O24]4−) possesses a δ-isomer Anderson-type structure, which is surrounded by four lattice water molecules and four [C7H15N4–NaH15(H2O)8]4+ cations in the crystal packing arrangement. The resulting double-sided tris-functionalized Anderson-type compound can function as highly effective heterogeneous photocatalysts for the copper(I)-catalyzed Huisgen azide-alkyne cycloaddition (Cu-AAC) reaction of terminal alkyne, benzyl halides, and sodium azide (acts as the azidonation and reducing agent) in aqueous media. Ultraviolet light irradiation enhances the catalytic activity of CuII-POM ~ 4.4 times of the “off” situation under reaction conditions of 0.00239 mmol cat., 80 °C, 8 h, 2 mL H2O, So that the isolated yields for the AAC reaction involving a variety of terminal alkynes and benzyl halides using the CuII-POM catalyst ranged between 19–97%. The current study is the first report about using an efficient and economical Cu(II)-POM/UV/NaN3 catalytic system in the Cu-AAC reaction and reveals its significant potential for applying to other Cu(I)-catalyzed reactions.
Trends estimation of obesity prevalence among South Asian young population: a systematic review and meta-analysis
Authors: Bansal Dipika , V. S. Mohammed Safeer , Devi Nagita , Boya Chandrasekhar , Dhora Babu Karamsetty , Dutta Pinaki
Published: January 2024

The premise for effective prevention and treatment of obesity is the availability of accurate prevalence figures. However, the prevalence of pediatric obesity and overweight in South Asian countries has seldom been analyzed. This article provides a comprehensive review and meta-analysis of studies on overweight and obesity to provide a more precise prevalence estimate. The study protocol was registered on PROSPERO (CRD42022320625). PubMed and Embase databases were comprehensively searched from inception till September 2023. The random-effects model was utilized to derive the pooled prevalence of obesity and overweight. Subgroup meta-analysis was used to assess variations in prevalence estimates across subgroups. A meta-regression analysis was also performed to assess the trend of overweight and obesity over the years. 152 studies were included with 489,525 participants. The pooled prevalence was 12.4 (95% CI 11.1–13.6) for overweight, 6.6% (95% CI 5.6–7.8) for obesity, and 19.3% (95% CI 17.1–21.7) for obesity and overweight. In subgroup analysis, Bangladesh reported a higher prevalence for both obesity (8.9%; 95% CI 4.9–13.9) and overweight (13.6%; 95% CI 9.2–18.8). Meta-regression analysis found a significant association between obesity prevalence and the publication year (β = 0.004; p = 0.03; R2 = 2.74%). The results of this study indicate a relatively higher prevalence of childhood obesity in South Asia, emphasizing the necessity for large-scale awareness efforts and context-specific preventative methods.
Visuo-motor lateralization in Apis mellifera: flight speed differences in foraging choices
Authors: Liga Davide , Stancher Gionata , Frasnelli Elisa
Published: January 2024

Evidence of lateralization has been provided in Apis mellifera in olfactory learning and social interactions, but not much is known about how it influences visuo-motor tasks. This study investigates visuo-motor biases in free-flying honeybees by analysing left/right choices related to foraging in a Y-maze. Individual bees were trained to associate a visual stimulus (a blue or yellow target) with a reward/punishment: the Blue + group was reinforced for the blue and punished for the yellow, and vice versa for the Yellow + group. In unrewarded tests, we assessed for each bee the directional choice for one of the two identical targets (12 trials with blue targets and 12 with yellow targets) placed in the left and right arms of the maze as well as the flight times to reach the target chosen. The results did not reveal a significant directional preference at the population level, but only at the individual level, with some individuals presenting a strong bias for choosing the right or left stimulus. However, the data revealed an interesting new factor: the influence of both direction and colour on flight times. Overall, bees took less time to choose the stimulus in the left arm. Furthermore, the yellow target, when previously associated with a punishment, was reached on average faster than the punished blue target, with a higher number of no-choices for punished blue targets than for punished yellow targets. This opens new perspectives not only on the study of lateralization in Apis mellifera, but also on the bees’ chromatic preferences.
Detection of caries lesions using a water-sensitive STIR sequence in dental MRI
Authors: Burian Egon , Lenhart Nicolas , Greve Tobias , Bodden Jannis , Burian Gintare , Palla Benjamin , Probst Florian , Probst Monika , Beer Meinrad , Folwaczny Matthias , Schwarting Julian
Published: January 2024

In clinical practice, diagnosis of suspected carious lesions is verified by using conventional dental radiography (DR), including panoramic radiography (OPT), bitewing imaging, and dental X-ray. The aim of this study was to evaluate the use of magnetic resonance imaging (MRI) for caries visualization. Fourteen patients with clinically suspected carious lesions, verified by standardized dental examination including DR and OPT, were imaged with 3D isotropic T2-weighted STIR (short tau inversion recovery) and T1 FFE Black bone sequences. Intensities of dental caries, hard tissue and pulp were measured and calculated as aSNR (apparent signal to noise ratio) and aHTMCNR (apparent hard tissue to muscle contrast to noise ratio) in both sequences. Imaging findings were then correlated to clinical examination results. In STIR as well as in T1 FFE black bone images, aSNR and aHTMCNR was significantly higher in carious lesions than in healthy hard tissue (p < 0.001). Using water-sensitive STIR sequence allowed for detecting significantly lower aSNR and aHTMCNR in carious teeth compared to healthy teeth (p = 0.01). The use of MRI for the detection of caries is a promising imaging technique that may complement clinical exams and traditional imaging.
Development of a novel disulfidptosis-related lncRNA signature for prognostic and immune response prediction in clear cell renal cell carcinoma
Authors: Wang Ning , Hu Yifeng , Wang Shasha , Xu Qin , Jiao Xiaojing , Wang Yanliang , Yan Lei , Cao Huixia , Shao Fengmin
Published: January 2024

Disulfidptosis, a novel form of regulated cell death, occurs due to the aberrant accumulation of intracellular cystine and other disulfides. Moreover, targeting disulfidptosis could identify promising approaches for cancer treatment. Long non-coding RNAs (lncRNAs) are known to be critically implicated in clear cell renal cell carcinoma (ccRCC) development. Currently, the involvement of disulfidptosis-related lncRNAs in ccRCC is yet to be elucidated. This study primarily dealt with identifying and validating a disulfidptosis-related lncRNAs-based signature for predicting the prognosis and immune landscape of individuals with ccRCC. Clinical and RNA sequencing data of ccRCC samples were accessed from The Cancer Genome Atlas (TCGA) database. Pearson correlation analysis was conducted for the identification of the disulfidptosis-related lncRNAs. Additionally, univariate Cox regression analysis, Least Absolute Shrinkage and Selection Operator Cox regression, and stepwise multivariate Cox analysis were executed to develop a novel risk prognostic model. The prognosis-predictive capacity of the model was then assessed using an integrated method. Variation in biological function was noted using GO, KEGG, and GSEA. Additionally, immune cell infiltration, the tumor mutational burden (TMB), and tumor immune dysfunction and exclusion (TIDE) scores were calculated to investigate differences in the immune landscape. Finally, the expression of hub disulfidptosis-related lncRNAs was validated using qPCR. We established a novel signature comprised of eight lncRNAs that were associated with disulfidptosis (SPINT1-AS1, AL121944.1, AC131009.3, AC104088.3, AL035071.1, LINC00886, AL035587.2, and AC007743.1). Kaplan–Meier and receiver operating characteristic curves demonstrated the acceptable predictive potency of the model. The nomogram and C-index confirmed the strong correlation between the risk signature and clinical decision-making. Furthermore, immune cell infiltration analysis and ssGSEA revealed significantly different immune statuses among risk groups. TMB analysis revealed the link between the high-risk group and high TMB. It is worth noting that the cumulative effect of the patients belonging to the high-risk group and having elevated TMB led to decreased patient survival times. The high-risk group depicted greater TIDE scores in contrast with the low-risk group, indicating greater potential for immune escape. Finally, qPCR validated the hub disulfidptosis-related lncRNAs in cell lines. The established novel signature holds potential regarding the prognosis prediction of individuals with ccRCC as well as predicting their responses to immunotherapy.
Plasma proteome profiling reveals the therapeutic effects of the PPAR pan-agonist chiglitazar on insulin sensitivity, lipid metabolism, and inflammation in type 2 diabetes
Authors: Wang Xingyue , Wang You , Hou Junjie , Liu Hongyang , Zeng Rong , Li Xiangyu , Han Mei , Li Qingrun , Ji Linong , Pan Desi , Jia Weiping , Zhong Wen , Xu Tao
Published: January 2024

Chiglitazar is a novel peroxisome proliferator-activated receptor (PPAR) pan-agonist, which passed phase III clinical trials and was newly approved in China for use as an adjunct to diet and exercise in glycemic control in adult patients with Type 2 Diabetes (T2D). To explore the circulating protein signatures associated with the administration of chiglitazar in T2D patients, we conducted a comparative longitudinal study using plasma proteome profiling. Of the 157 T2D patients included in the study, we administered chiglitazar to a specific group, while the controls were given either placebo or sitagliptin. The plasma proteomes were profiled at baseline and 12 and 24 weeks post-treatment using data-independent acquisition mass spectrometry (DIA-MS). Our study indicated that 13 proteins were associated with chiglitazar treatment in T2D patients, including 10 up-regulated proteins (SHBG, TF, APOA2, APOD, GSN, MBL2, CFD, PGLYRP2, A2M, and APOA1) and 3 down-regulated proteins (PRG4, FETUB, and C2) after treatment, which were implicated in the regulation of insulin sensitivity, lipid metabolism, and inflammation response. Our study provides insight into the response of chiglitazar treatment from a proteome perspective and demonstrates the multi-faceted effects of chiglitazar in T2D patients, which will help the clinical application of chiglitazar and further study of its action mechanism.
Selenoprotein P expression in glioblastoma as a regulator of ferroptosis sensitivity: preservation of GPX4 via the cycling-selenium storage
Authors: Zheng Xi , Toyama Takashi , Siu Stephanie , Kaneko Takayuki , Sugiura Hikari , Yamashita Shota , Shimoda Yoshiteru , Kanamori Masayuki , Arisawa Kotoko , Endo Hidenori , Saito Yoshiro
Published: January 2024

Glioblastoma (GBM) is one of the most aggressive and deadly brain tumors; however, its current therapeutic strategies are limited. Selenoprotein P (SeP; SELENOP, encoded by the SELENOP gene) is a unique selenium-containing protein that exhibits high expression levels in astroglia. SeP is thought to be associated with ferroptosis sensitivity through the induction of glutathione peroxidase 4 (GPX4) via selenium supplementation. In this study, to elucidate the role of SeP in GBM, we analyzed its expression in GBM patients and found that SeP expression levels were significantly higher when compared to healthy subjects. Knock down of SeP in cultured GBM cells resulted in a decrease in GPX1 and GPX4 protein levels. Under the same conditions, cell death caused by RSL3, a ferroptosis inducer, was enhanced, however this enhancement was canceled by supplementation of selenite. These results indicate that SeP expression contributes to preserving GPX and selenium levels in an autocrine/paracrine manner, i.e., SeP regulates a dynamic cycling-selenium storage system in GBM. We also confirmed the role of SeP expression in ferroptosis sensitivity using patient-derived primary GBM cells. These findings indicate that expression of SeP in GBM can be a significant therapeutic target to overcome anticancer drug resistance.
Clinical predictors of prognosis in stroke patients after endovascular therapy
Authors: Wang Yugang , Yuan Xingyun , Kang Yonggang , Yu Liping , Chen Wanhong , Fan Gang
Published: January 2024

Endovascular therapy (EVT) is effective in the treatment of large vascular occlusive stroke. However, many factors are associated with the outcomes of acute ischemic stroke (AIS) after EVT. This study aimed to identify the main factors related to the prognosis of AIS patients after EVT. We analyzed the clinical data of AIS patients in the neurology department of our medical center from June 2017 to August 2021 following treatment with EVT. The data included the patients’ blood pressure upon admission, blood glucose concentration, National Institutes of Health Stroke Scale (NIHSS) score, 90-day modified Rankin scale (mRs) score follow-up data, and time from LKN to the successful groin puncture (GP). A good outcome was defined as a 90-day mRs score of 0–2, and a poor outcome was defined as a 90-day mRs score of 3–6. A total of 144 patients were included in the study. Admission, smoking, and LKN-to-GP time, NIHSS score of 6–12 was found to be relevant to the prognosis. The results of multivariate analysis showed that prognosis was significantly influenced by baseline NIHSS (odds ratio = 3.02; 95% confidence interval, 2.878–4.252; P = 0.001), LKN-to-GP time (odds ratio = 2.17; 95% confidence interval, 1.341–2.625; P = 0.003), and time stratification (6–12 h) (odds ratio = 4.22; 95% confidence interval, 2.519–5.561; P = 0.001). Our study indicated that smoking, baseline NIHSS score, and LKN-to-GP time were the risk factors for a poor outcome in stroke patients following an EVT. Quitting smoking and shortening LKN time to GP should improve the outcome of AIS after EVT.
A destabilizing Y891D mutation in activated EGFR impairs sensitivity to kinase inhibition
Authors: Lenchner Daniel S. , Petrova Zaritza O. , Hunihan Lisa , Ashtekar Kumar D. , Walther Zenta , Wilson Frederick H.
Published: January 2024

EGFR tyrosine kinase inhibitors (TKIs) have transformed the treatment of EGFR-mutated non-small cell lung carcinoma (NSCLC); however, therapeutic resistance remains a clinical challenge. Acquired secondary EGFR mutations that increase ATP affinity and/or impair inhibitor binding are well-described mediators of resistance. Here we identify a de novo EGFR Y891D secondary alteration in a NSCLC with EGFR L858R. Acquired EGFR Y891D alterations were previously reported in association with resistance to first generation EGFR TKIs. Functional studies in Ba/F3 cells demonstrate reduced TKI sensitivity of EGFR L858R + Y891D, with the greatest reduction observed for first and second generation TKIs. Unlike other EGFR mutations associated with TKI resistance, Y891D does not significantly alter ATP affinity or promote steric hindrance to inhibitor binding. Our data suggest that the Y891D mutation destabilizes EGFR L858R, potentially generating a population of misfolded receptor with preserved signaling capacity but reduced sensitivity to EGFR inhibitors. These findings raise the possibility of protein misfolding as a mechanism of resistance to EGFR inhibition in EGFR-mutated NSCLC.
LiLA: lipid lung-based ATLAS built through a comprehensive workflow designed for an accurate lipid annotation
Authors: Fernández Requena Belén , Nadeem Sajid , Reddy Vineel P. , Naidoo Vanessa , Glasgow Joel N. , Steyn Adrie J. C. , Barbas Coral , Gonzalez-Riano Carolina
Published: January 2024

Accurate lipid annotation is crucial for understanding the role of lipids in health and disease and identifying therapeutic targets. However, annotating the wide variety of lipid species in biological samples remains challenging in untargeted lipidomic studies. In this work, we present a lipid annotation workflow based on LC-MS and MS/MS strategies, the combination of four bioinformatic tools, and a decision tree to support the accurate annotation and semi-quantification of the lipid species present in lung tissue from control mice. The proposed workflow allowed us to generate a lipid lung-based ATLAS (LiLA), which was then employed to unveil the lipidomic signatures of the Mycobacterium tuberculosis infection at two different time points for a deeper understanding of the disease progression. This workflow, combined with manual inspection strategies of MS/MS data, can enhance the annotation process for lipidomic studies and guide the generation of sample-specific lipidome maps. LiLA serves as a freely available data resource that can be employed in future studies to address lipidomic alterations in mice lung tissue.
Human leukocyte antigen-DQA1*04:01 and rs2040406 variants are associated with elevated risk of childhood Burkitt lymphoma
Authors: Liu Zhiwei , Luo Yang , Kirimunda Samuel , Verboom Murielle , Onabajo Olusegun O. , Gouveia Mateus H. , Ogwang Martin D. , Kerchan Patrick , Reynolds Steven J. , Tenge Constance N. , Were Pamela A. , Kuremu Robert T. , Wekesa Walter N. , Masalu Nestory , Kawira Esther , Kinyera Tobias , Otim Isaac , Legason Ismail D. , Nabalende Hadijah , Dhudha Herry , Ayers Leona W. , Bhatia Kishor , Goedert James J. , Cole Nathan , Luo Wen , Liu Jia , Manning Michelle , Hicks Belynda , Prokunina-Olsson Ludmila , Chagaluka George , Johnston W. Thomas , Mutalima Nora , Borgstein Eric , Liomba George N. , Kamiza Steve , Mkandawire Nyengo , Mitambo Collins , Molyneux Elizabeth M. , Newton Robert , Hsing Ann W. , Mensah James E. , Adjei Anthony A. , Hutchinson Amy , Carrington Mary , Yeager Meredith , Blasczyk Rainer , Chanock Stephen J. , Raychaudhuri Soumya , Mbulaiteye Sam M.
Published: January 2024

Burkitt lymphoma (BL) is responsible for many childhood cancers in sub-Saharan Africa, where it is linked to recurrent or chronic infection by Epstein-Barr virus or Plasmodium falciparum. However, whether human leukocyte antigen (HLA) polymorphisms, which regulate immune response, are associated with BL has not been well investigated, which limits our understanding of BL etiology. Here we investigate this association among 4,645 children aged 0-15 years, 800 with BL, enrolled in Uganda, Tanzania, Kenya, and Malawi. HLA alleles are imputed with accuracy >90% for HLA class I and 85-89% for class II alleles. BL risk is elevated with HLA-DQA1*04:01 (adjusted odds ratio [OR] = 1.61, 95% confidence interval [CI] = 1.32-1.97, P = 3.71 × 10−6), with rs2040406(G) in HLA-DQA1 region (OR = 1.43, 95% CI = 1.26-1.63, P = 4.62 × 10−8), and with amino acid Gln at position 53 versus other variants in HLA-DQA1 (OR = 1.36, P = 2.06 × 10−6). The associations with HLA-DQA1*04:01 (OR = 1.29, P = 0.03) and rs2040406(G) (OR = 1.68, P = 0.019) persist in mutually adjusted models. The higher risk rs2040406(G) variant for BL is associated with decreased HLA-DQB1 expression in eQTLs in EBV transformed lymphocytes. Our results support the role of HLA variation in the etiology of BL and suggest that a promising area of research might be understanding the link between HLA variation and EBV control.
Two somatic mutations in the androgen receptor N-terminal domain are oncogenic drivers in hepatocellular carcinoma
Authors: Ren Qian-Nan , Huang Dan-Hui , Zhang Xiao-Nan , Wang Yue-Ning , Zhou Yu-Feng , Zhang Mei-Yin , Wang Shuo-Cheng , Mai Shi-Juan , Wu De-Hua , Wang Hui-Yun
Published: January 2024

The androgen receptor (AR) plays an important role in male-dominant hepatocellular carcinoma, and specific acquired somatic mutations of AR have been observed in HCC patients. Our previous research have established the role of AR wild type as one of the key oncogenes in hepatocarcinogenesis. However, the role of hepatic acquired somatic mutations of AR remains unknown. In this study, we identify two crucial acquired somatic mutations, Q62L and E81Q, situated close to the N-terminal activation function domain-1 of AR. These mutations lead to constitutive activation of AR, both independently and synergistically with androgens, making them potent driver oncogene mutations. Mechanistically, these N-terminal AR somatic mutations enhance de novo lipogenesis by activating sterol regulatory element-binding protein-1 and promote glycogen accumulation through glycogen phosphorylase, brain form, thereby disrupting the AMPK pathway and contributing to tumorigenesis. Moreover, the AR mutations show sensitivity to the AMPK activator A769662. Overall, this study establishes the role of these N- terminal hepatic mutations of AR as highly malignant oncogenic drivers in hepatocarcinogenesis and highlights their potential as therapeutic targets for patients harboring these somatic mutations.
A biphenotypic lymphocyte subset displays both T- and B-cell functionalities
Authors: zhang Yifan , Guo Cuiyuan , Zhou Yigong , Zhang Wenhong , Zhu Zhaoqin , Wang Wanhai , Wan Yanmin
Published: January 2024

T cell/B cell mixed phenotypic lymphocytes have been observed in different disease contexts, yet their presence and function in physiological conditions remain elusive. Here, we provide evidence for the existence of a lymphocyte subset endogenously expressing both T- and B-cell lineage markers in mice. The majority of these T/B phenotypic lymphocytes (CD3+CD19+) show an origin of pro/pre B cells and distribute widely in mouse bone marrow, lymph nodes, spleen, and peripheral blood. Functional assays show that these biphenotypic lymphocytes can be activated through stimulating TCR or BCR signaling pathways. Moreover, we show that these cells actively participate both the humoral and cellular immune responses elicited by vaccination. Compared to conventional T cells, these biphenotypic lymphocytes can secrete a higher level of IL-2 but a lower level of TNF-α upon antigen specific stimulation. An equivalent lymphocyte subset is found in freshly isolated human PBMCs and exhibits similar functionality, albeit at a lower frequency than in mice.