bluuebunny/crossref_metadata_2025 huggingface dataset:
Plato, Socrates, and Confederate Monuments
Authors: Berman Scott
Published: March 2024

What is the best way to respond to monuments in our communities if they represent people who stood for harmful ideas and/or societal structures? I start with the assumption that it would be best for everyone if all of the harmful monuments were removed from our public squares. The more interesting question is: Why would it be best? I will examine critically two different explanations as to why it would be best: one, Plato's, which rests on the harmful non-intellectual influences of images and the other, Socrates’, which rests on the harmful intellectual influences of those images. In the end, I shall argue that Socrates got it right and Plato wrong due to the former's ability to explain human behaviour and the latter's surprising lack of that same ability, despite how widely it is believed. If the argument is correct, it will have deep and widespread implications for how we educate our children and ourselves about every important aspect of the human condition.
What Is Sexual Intimacy?
Authors: Settegast Sascha
Published: March 2024

What is the role of intimacy in sex? The two culturally dominant views on this matter both share the implicit assumption that sex is genuinely intimate only when connected to romance, and hence that sex and intimacy stand in a contingent relationship: it is possible to have good sex without it. Liberals embrace this possibility and affirm the value of casual sex, while conservatives attempt to safeguard intimacy by insisting on romantic exclusivity. I reject their shared assumption and argue for a necessary connection between intimacy and sex, in that sexual activity as such aims at a specific form of intimacy, irrespective of whether it takes place in casual encounters or romantic relationships, and the difference between good and bad sex consists in whether this end is attained. To defend this view, I develop a general account of intimacy and apply it to isolate its specifically sexual form.
Mid‐Air Collisions Control the Wavelength of Aeolian Sand Ripples
Authors: Huo Xinghui , Herrmann Hans J. , Zhang Jie , Huang Ning
Published: March 2024

The wavelength of aeolian sand ripples increases with wind velocity, but the cause for this increase remained unclear until now. Using numerical simulations, we find that the relationship between the wind strength and the initial wavelength disappears without mid‐air collisions, which means that mid‐air collisions crucially contribute to the initial wavelength of ripples. As wind strength increases, the average hop length of non‐colliding particles decreases. Affected by the bed surface topography and the non‐uniform mid‐air colliding probability along the wavy surface, non‐colliding particles cause a surface modulated erosion/deposition flux. The first order contribution of the flux fluctuation destabilizes the original bed surface and has a wind‐dependent phase shift with respect to the surface profile. This phase shift leads to an initial wavelength that increases with wind velocity. Based on these findings we derive the scaling law for the initial wavelength of aeolian sand ripples, which agrees well with experimental results. A weak non‐linear relationship between ripple wavelength and wind velocity has been found, especially for large wind strengths.
Optimal Allocation Strategies of Plant Calcium on Qinghai–Tibetan Plateau
Authors: Jiao Chaolian , Zhang Jiahui , Wang Xiaochun , He Nianpeng
Published: March 2024

Calcium (Ca) is an essential nutrient for plant growth and development. As Ca plays crucial roles in plant structure and signaling, its allocation strategies among organs can reflect the optimization of plant functions and responses to the environment. However, the allocation strategies and spatial variation of plant Ca at the community level have not been systematically determined on a large scale despite their potential link to ecosystem functions. Here, we mapped community‐level Ca content and density (1 × 1 km) using grid‐investigated data on leaves, branches, trunks, and roots from 680 sampling sites on the Qinghai–Tibetan Plateau (TP). Specifically, the Ca content and density of the leaves, branches, trunks, and roots of TP plants were 10.90, 6.09, 1.85, and 15.62 mg g−1 and 3.29, 17.10, 12.27, and 12.06 g m−2, respectively. Importantly, plant adopted optimal allocation strategies with allocating more Ca to roots in stressed ecosystems to maintain survival while more Ca to leaves in suitable forests for growth, that is the proposed survival/growth‐driven allocation hypothesis. Furthermore, plants optimally absorbed more nutrients in stressed environments for defense, as demonstrated by the higher Ca content and lower Ca use efficiency in deserts and grasslands than in forests. Furthermore, the strong evidence for the proposed hypothesis was the spatial pattern of plant Ca content decreasing from the northwest to the southeast. Our findings reveal the optimal nutrient allocation strategies and provide data support (Ca content and density) for assessing plant nutrient status in different types of ecosystems.
Exploring Alfv�n Waves Across Space—and Disciplines
Authors: Keiling Andreas
Published: March 2024

A new book presents an interdisciplinary review of Alfv�n wave research, sharing the latest insights from the solar, planetary, and terrestrial sciences.
Bayesian interim analysis for prospective randomized studies: reanalysis of the acute myeloid leukemia HOVON 132 clinical trial
Authors: van der Maas Niek G. , Versluis Jurjen , Nasserinejad Kazem , van Rosmalen Joost , Pabst Thomas , Maertens Johan , Breems Dimitri , Manz Markus , Cloos Jacqueline , Ossenkoppele Gert J. , Floisand Yngvar , Gradowska Patrycja , Löwenberg Bob , Huls Gerwin , Postmus Douwe , Pignatti Francesco , Cornelissen Jan J.
Published: March 2024

Randomized controlled trials (RCTs) are the gold standard to establish the benefit-risk ratio of novel drugs. However, the evaluation of mature results often takes many years. We hypothesized that the addition of Bayesian inference methods at interim analysis time points might accelerate and enforce the knowledge that such trials may generate. In order to test that hypothesis, we retrospectively applied a Bayesian approach to the HOVON 132 trial, in which 800 newly diagnosed AML patients aged 18 to 65 years were randomly assigned to a “7 + 3” induction with or without lenalidomide. Five years after the first patient was recruited, the trial was negative for its primary endpoint with no difference in event-free survival (EFS) between experimental and control groups (hazard ratio [HR] 0.99, p = 0.96) in the final conventional analysis. We retrospectively simulated interim analyses after the inclusion of 150, 300, 450, and 600 patients using a Bayesian methodology to detect early lack of efficacy signals. The HR for EFS comparing the lenalidomide arm with the control treatment arm was 1.21 (95% CI 0.81–1.69), 1.05 (95% CI 0.86–1.30), 1.00 (95% CI 0.84–1.19), and 1.02 (95% CI 0.87–1.19) at interim analysis 1, 2, 3 and 4, respectively. Complete remission rates were lower in the lenalidomide arm, and early deaths more frequent. A Bayesian approach identified that the probability of a clinically relevant benefit for EFS (HR < 0.76, as assumed in the statistical analysis plan) was very low at the first interim analysis (1.2%, 0.6%, 0.4%, and 0.1%, respectively). Similar observations were made for low probabilities of any benefit regarding CR. Therefore, Bayesian analysis significantly adds to conventional methods applied for interim analysis and may thereby accelerate the performance and completion of phase III trials.
Regulatory T cells expressing CD19-targeted chimeric antigen receptor restore homeostasis in Systemic Lupus Erythematosus
Authors: Doglio M. , Ugolini A. , Bercher-Brayer C. , Camisa B. , Toma C. , Norata R. , Del Rosso S. , Greco R. , Ciceri F. , Sanvito F. , Casucci M. , Manfredi A. A. , Bonini C.
Published: March 2024

Systemic Lupus Erythematosus (SLE) is a progressive disease leading to immune-mediated tissue damage, associated with an alteration of lymphoid organs. Therapeutic strategies involving regulatory T (Treg) lymphocytes, which physiologically quench autoimmunity and support long-term immune tolerance, are considered, as conventional treatment often fails. We describe here a therapeutic strategy based on Tregs overexpressing FoxP3 and harboring anti-CD19 CAR (Fox19CAR-Tregs). Fox19CAR-Tregs efficiently suppress proliferation and activity of B cells in vitro, which are relevant for SLE pathogenesis. In an humanized mouse model of SLE, a single infusion of Fox19CAR-Tregs restricts autoantibody generation, delay lymphopenia (a key feature of SLE) and restore the human immune system composition in lymphoid organs, without detectable toxicity. Although a short survival, SLE target organs appear to be protected. In summary, Fox19CAR-Tregs can break the vicious cycle leading to autoimmunity and persistent tissue damage, representing an efficacious and safe strategy allowing restoration of homeostasis in SLE.
High-throughput prediction of protein conformational distributions with subsampled AlphaFold2
Authors: Monteiro da Silva Gabriel , Cui Jennifer Y. , Dalgarno David C. , Lisi George P. , Rubenstein Brenda M.
Published: March 2024

This paper presents an innovative approach for predicting the relative populations of protein conformations using AlphaFold 2, an AI-powered method that has revolutionized biology by enabling the accurate prediction of protein structures. While AlphaFold 2 has shown exceptional accuracy and speed, it is designed to predict proteins’ ground state conformations and is limited in its ability to predict conformational landscapes. Here, we demonstrate how AlphaFold 2 can directly predict the relative populations of different protein conformations by subsampling multiple sequence alignments. We tested our method against nuclear magnetic resonance experiments on two proteins with drastically different amounts of available sequence data, Abl1 kinase and the granulocyte-macrophage colony-stimulating factor, and predicted changes in their relative state populations with more than 80% accuracy. Our subsampling approach worked best when used to qualitatively predict the effects of mutations or evolution on the conformational landscape and well-populated states of proteins. It thus offers a fast and cost-effective way to predict the relative populations of protein conformations at even single-point mutation resolution, making it a useful tool for pharmacology, analysis of experimental results, and predicting evolution.
Uncovering structural themes across cilia microtubule inner proteins with implications for human cilia function
Authors: Andersen Jens S. , Vijayakumaran Aaran , Godbehere Christopher , Lorentzen Esben , Mennella Vito , Schou Kenneth Bødtker
Published: March 2024

Centrosomes and cilia are microtubule-based superstructures vital for cell division, signaling, and motility. The once thought hollow lumen of their microtubule core structures was recently found to hold a rich meshwork of microtubule inner proteins (MIPs). To address the outstanding question of how distinct MIPs evolved to recognize microtubule inner surfaces, we applied computational sequence analyses, structure predictions, and experimental validation to uncover evolutionarily conserved microtubule- and MIP-binding modules named NWE, SNYG, and ELLEn, and PYG and GFG-repeat by their signature motifs. These modules intermix with MT-binding DM10-modules and Mn-repeats in 24 Chlamydomonas and 33 human proteins. The modules molecular characteristics provided keys to identify elusive cross-species homologs, hitherto unknown human MIP candidates, and functional properties for seven protein subfamilies, including the microtubule seam-binding NWE and ELLEn families. Our work defines structural innovations that underpin centriole and axoneme assembly and demonstrates that MIPs co-evolved with centrosomes and cilia.
Trade-offs shaping transmission of sylvatic dengue and Zika viruses in monkey hosts
Authors: Hanley Kathryn A. , Cecilia Hélène , Azar Sasha R. , Moehn Brett A. , Gass Jordan T. , Oliveira da Silva Natalia I. , Yu Wanqin , Yun Ruimei , Althouse Benjamin M. , Vasilakis Nikos , Rossi Shannan L.
Published: March 2024

Mosquito-borne dengue (DENV) and Zika (ZIKV) viruses originated in Old World sylvatic (forest) cycles involving monkeys and canopy-living Aedes mosquitoes. Both viruses spilled over into human transmission and were translocated to the Americas, opening a path for spillback into Neotropical sylvatic cycles. Studies of the trade-offs that shape within-host dynamics and transmission of these viruses are lacking, hampering efforts to predict spillover and spillback. We infected a native, Asian host species (cynomolgus macaque) and a novel, American host species (squirrel monkey) with sylvatic strains of DENV-2 or ZIKV via mosquito bite. We then monitored aspects of viral replication (viremia), innate and adaptive immune response (natural killer (NK) cells and neutralizing antibodies, respectively), and transmission to mosquitoes. In both hosts, ZIKV reached high titers that translated into high transmission to mosquitoes; in contrast DENV-2 replicated to low levels and, unexpectedly, transmission occurred only when serum viremia was below or near the limit of detection. Our data reveal evidence of an immunologically-mediated trade-off between duration and magnitude of virus replication, as higher peak ZIKV titers are associated with shorter durations of viremia, and higher NK cell levels are associated with lower peak ZIKV titers and lower anti-DENV-2 antibody levels. Furthermore, patterns of transmission of each virus from a Neotropical monkey suggest that ZIKV has greater potential than DENV-2 to establish a sylvatic transmission cycle in the Americas.
Autophagy-mediated degradation of integumentary tapetum is critical for embryo pattern formation
Authors: Zhao Lin-lin , Chen Ru , Bai Ziyu , Liu Junyi , Zhang Yuhao , Zhong Yicheng , Sun Meng-xiang , Zhao Peng
Published: March 2024

Autophagy modulates the degradation and recycling of intracellular materials and contributes to male gametophyte development and male fertility in plants. However, whether autophagy participates in seed development remains largely unknown. Here, we demonstrate that autophagy is crucial for timely programmed cell death (PCD) in the integumentary tapetum, the counterpart of anther tapetum, influencing embryo pattern formation and seed viability. Inhibition of autophagy resulted in delayed PCD of the integumentary tapetum and defects in embryo patterning. Cell-type-specific restoration of autophagic activities revealed that the integumentary tapetum plays a non-autonomous role in embryo patterning. Furthermore, high-throughput, comprehensive lipidomic analyzes uncovered an unexpected seed-developmental-stage-dependent role of autophagy in seed lipid metabolism: it contributes to triacylglycerol degradation before fertilization and to triacylglycerol biosynthesis after fertilization. This study highlights the critical role of autophagy in regulating timely integumentary tapetum PCD and reveals its significance in seed lipid metabolism and viability.
Replication study on the role of dopamine-dependent prefrontal reactivations in human extinction memory retrieval
Authors: Andres Elena , Chuan-Peng Hu , Gerlicher Anna M. V. , Meyer Benjamin , Tüscher Oliver , Kalisch Raffael
Published: March 2024

Even after successful extinction, conditioned fear can return. Strengthening the consolidation of the fear-inhibitory safety memory formed during extinction is one way to counteract return of fear. In a previous study, we found that post-extinction L-DOPA administration improved extinction memory retrieval 24 h later. Furthermore, spontaneous post-extinction reactivations of a neural activation pattern evoked in the ventromedial prefrontal cortex (vmPFC) during extinction predicted extinction memory retrieval, L-DOPA increased the number of these reactivations, and this mediated the effect of L-DOPA on extinction memory retrieval. Here, we conducted a preregistered replication study of this work in healthy male participants. We confirm that spontaneous post-extinction vmPFC reactivations predict extinction memory retrieval. This predictive effect, however, was only observed 90 min after extinction, and was not statistically significant at 45 min as in the discovery study. In contrast to our previous study, we find no evidence that L-DOPA administration significantly enhances retrieval and that this is mediated by enhancement of the number of vmPFC reactivations. However, additional non-preregistered analyses reveal a beneficial effect of L-DOPA on extinction retrieval when controlling for the trait-like stable baseline levels of salivary alpha-amylase enzymatic activity. Further, trait salivary alpha-amylase negatively predicts retrieval, and this effect is reduced by L-DOPA treatment. Importantly, the latter findings result from non-preregistered analyses and thus further investigation is needed.
Adjuvant nivolumab, capecitabine or the combination in patients with residual triple-negative breast cancer: the OXEL randomized phase II study
Authors: Lynce Filipa , Mainor Candace , Donahue Renee N. , Geng Xue , Jones Greg , Schlam Ilana , Wang Hongkun , Toney Nicole J. , Jochems Caroline , Schlom Jeffrey , Zeck Jay , Gallagher Christopher , Nanda Rita , Graham Deena , Stringer-Reasor Erica M. , Denduluri Neelima , Collins Julie , Chitalia Ami , Tiwari Shruti , Nunes Raquel , Kaltman Rebecca , Khoury Katia , Gatti-Mays Margaret , Tarantino Paolo , Tolaney Sara M. , Swain Sandra M. , Pohlmann Paula , Parsons Heather A. , Isaacs Claudine
Published: March 2024

Chemotherapy and immune checkpoint inhibitors have a role in the post-neoadjuvant setting in patients with triple-negative breast cancer (TNBC). However, the effects of nivolumab, a checkpoint inhibitor, capecitabine, or the combination in changing peripheral immunoscore (PIS) remains unclear. This open-label randomized phase II OXEL study (NCT03487666) aimed to assess the immunologic effects of nivolumab, capecitabine, or the combination in terms of the change in PIS (primary endpoint). Secondary endpoints included the presence of ctDNA, toxicity, clinical outcomes at 2-years and association of ctDNA and PIS with clinical outcomes. Forty-five women with TNBC and residual invasive disease after standard neoadjuvant chemotherapy were randomized to nivolumab, capecitabine, or the combination. Here we show that treatment with immunotherapy containing arms (nivolumab or a combination of nivolumab plus capecitabine) leads to an increase in PIS from baseline to week 6 compared with capecitabine alone, meeting the pre-specified primary endpoint. In addition, the presence of circulating tumor DNA (ctDNA) is associated with disease recurrence, with no new safety signals in the combination arm. Our results provide efficacy and safety data on this combination in TNBC and support further development of PIS and ctDNA analyses to identify patients at high risk of recurrence.
Synaptically-targeted long non-coding RNA SLAMR promotes structural plasticity by increasing translation and CaMKII activity
Authors: Espadas Isabel , Wingfield Jenna L. , Nakahata Yoshihisa , Chanda Kaushik , Grinman Eddie , Ghosh Ilika , Bauer Karl E. , Raveendra Bindu , Kiebler Michael A. , Yasuda Ryohei , Rangaraju Vidhya , Puthanveettil Sathyanarayanan
Published: March 2024

Long noncoding RNAs (lncRNAs) play crucial roles in maintaining cell homeostasis and function. However, it remains largely unknown whether and how neuronal activity impacts the transcriptional regulation of lncRNAs, or if this leads to synapse-related changes and contributes to the formation of long-term memories. Here, we report the identification of a lncRNA, SLAMR, which becomes enriched in CA1-hippocampal neurons upon contextual fear conditioning but not in CA3 neurons. SLAMR is transported along dendrites via the molecular motor KIF5C and is recruited to the synapse upon stimulation. Loss of function of SLAMR reduces dendritic complexity and impairs activity-dependent changes in spine structural plasticity and translation. Gain of function of SLAMR, in contrast, enhances dendritic complexity, spine density, and translation. Analyses of the SLAMR interactome reveal its association with CaMKIIα protein through a 220-nucleotide element also involved in SLAMR transport. A CaMKII reporter reveals a basal reduction in CaMKII activity with SLAMR loss-of-function. Furthermore, the selective loss of SLAMR function in CA1 disrupts the consolidation of fear memory in male mice, without affecting their acquisition, recall, or extinction, or spatial memory. Together, these results provide new molecular and functional insight into activity-dependent changes at the synapse and consolidation of contextual fear.
S100A8/A9 as a prognostic biomarker with causal effects for post-acute myocardial infarction heart failure
Authors: Ma Jie , Li Yang , Li Ping , Yang Xinying , Zhu Shuolin , Ma Ke , Gao Fei , Gao Hai , Zhang Hui , Ma Xin-liang , Du Jie , Li Yulin
Published: March 2024

Heart failure is the prevalent complication of acute myocardial infarction. We aim to identify a biomarker for heart failure post-acute myocardial infarction. This observational study includes 1062 and 1043 patients with acute myocardial infarction in the discovery and validation cohorts, respectively. The outcomes are in-hospital and long-term heart failure events. S100A8/A9 is screened out through proteomic analysis, and elevated circulating S100A8/A9 is independently associated with heart failure in discovery and validation cohorts. Furthermore, the predictive value of S100A8/A9 is superior to the traditional biomarkers, and the addition of S100A8/A9 improves the risk estimation using traditional risk factors. We finally report causal effect of S100A8/A9 on heart failure in three independent cohorts using Mendelian randomization approach. Here, we show that S100A8/A9 is a predictor and potentially causal medicator for heart failure post-acute myocardial infarction.
3D molecular generative framework for interaction-guided drug design
Authors: Zhung Wonho , Kim Hyeongwoo , Kim Woo Youn
Published: March 2024

Deep generative modeling has a strong potential to accelerate drug design. However, existing generative models often face challenges in generalization due to limited data, leading to less innovative designs with often unfavorable interactions for unseen target proteins. To address these issues, we propose an interaction-aware 3D molecular generative framework that enables interaction-guided drug design inside target binding pockets. By leveraging universal patterns of protein-ligand interactions as prior knowledge, our model can achieve high generalizability with limited experimental data. Its performance has been comprehensively assessed by analyzing generated ligands for unseen targets in terms of binding pose stability, affinity, geometric patterns, diversity, and novelty. Moreover, the effective design of potential mutant-selective inhibitors demonstrates the applicability of our approach to structure-based drug design.
Stability, homogeneity and measurement uncertainty estimation of PVP-I solutions for the application on oro and nasopharynx against SARS-CoV-2
Authors: Moniruzzaman Md. , Razu Mamudul Hasan , Rahman Sad Al Rezwan , Kundu Nayan Kumer , Kamal Sabiha , Khan Mala
Published: March 2024

Aqueous solution containing different concentration (0.5, 0.6 and 1.0%) (w/v) of Polyvinyl pyrrolodon-Iodine (PVP-I) complex, a well-known antiseptic; is prepared and the stability and homogeneity of these solution is assessed as per the ICH Guidelines and International Harmonized Protocol respectively. The solutions were found to be sufficiently homogeneous and stable for a year at 25 °C (60%RH). Measurement uncertainty of the prepared PVP-I solutions were estimated by identifying possible sources of uncertainty using Ishikawa diagram and preparing uncertainty budget based on scope of calibration laboratory. The stable and homogenized PVP-I solution is to be used in a clinical trial for the application on oro and nasopharynx against novel SARS-CoV-2 Virus.
Flying fast improves aerodynamic economy of heavier birds
Authors: Bishop Charles M. , Halsey Lewis G. , Askew Graham N.
Published: March 2024

A paradox of avian long-distance migrations is that birds must greatly increase their body mass prior to departure, yet this is presumed to substantially increase their energy cost of flight. However, here we show that when homing pigeons flying in a flock are loaded with ventrally located weight, both their heart rate and estimated energy expenditure rise by a remarkably small amount. The net effect is that costs per unit time increase only slightly and per unit mass they decrease. We suggest that this is because these homing flights are relatively fast, and consequently flight costs associated with increases in body parasite drag dominate over those of weight support, leading to an improvement in mass-specific flight economy. We propose that the relatively small absolute aerodynamic penalty for carrying enlarged fuel stores and flight muscles during fast flight has helped to select for the evolution of long-distance migration.
Community pharmacist-led point-of-care eGFR screening: early detection of chronic kidney disease in high-risk patients
Authors: Jairoun Ammar Abdulrahman , Al-Hemyari Sabaa Saleh , Shahwan Moyad , Zyoud Samer H. , El-Dahiyat Faris
Published: March 2024

Adherence to scheduled physician screenings for renal function monitoring in patients with chronic kidney disease (CKD) or those at high risk remains suboptimal despite the endorsement of regular screenings by several clinical practice guidelines. Our study aims to assess the effectiveness of a point-of-care CKD screening program led by these pharmacists using the PICCOLO device while recognizing the unique position of community pharmacists in primary care. We conducted an 11-month prospective point-of-care interventional research study in the United Arab Emirates to evaluate the performance of a community pharmacist-led CKD screening program for high-risk patients. Six diverse community pharmacies were selected based on staff availability, patient volume, and their offered range of services. Eligible individuals with risk factors for CKD were identified during medication evaluations. The PICCOLO Comprehensive Metabolic Panel facilitated on-site blood analysis, delivering estimated Glomerular Filtration Rate (eGFR) results within 10 to 15 min. Data also included eGFR categories, demographic information, and insights into lifestyle and health habits collected through a questionnaire. Pharmacists conducted comprehensive medication reviews and offered referrals and lifestyle guidance as part of the program. The study encompassed a total of 400 patients, with an average age of 69 ± 13.4 years within the study cohort. Notably, 38.8% (155 individuals) of the 400 patients were found to have undiagnosed CKD stages 3–5. Univariate logistic regression analysis revealed a significant association between a higher incidence of CKD stages 3–5 and factors such as older age, a history of hypertension, vascular disease, and diabetes mellitus. In the multivariate regression model, age and a history of diabetes mellitus emerged as significant predictors of an elevated risk of CKD. This study sheds light on the viability and impact of CKD screening programs conducted by community pharmacists, particularly in detecting CKD stages 3–5. The findings have implications for healthcare policies, as they can influence the enhancement of early detection and management of CKD. Moreover, these insights may catalyze focused screening initiatives and strengthen collaboration between community pharmacies and healthcare systems to benefit patients at high risk of CKD.
Analytical formulation of spatiotemporal modulated graphene-based waveguides using Floquet-Bloch theory
Authors: Valizadeh Mahsa , Yousefi Leila , Miri MirFaez
Published: March 2024

In this work, an analytical model to study graphene-based spatiotemporal modulated structures is developed and verified through comparison with full wave numerical simulations. Graphene is an ideal material for realizing spatiotemporal modulated structures at high frequencies of THz and optics. In this analysis, the electromagnetic response of studied structures is expressed in terms of weighted Floquet-Bloch modes supported by the structure, while graphene is modeled by a spatiotemporal modulated surface current that imposes certain boundary conditions on the modes. The developed analytical technique is a comprehensive tool and can be used for accurate modeling of different kinds of spatiotemporal devices including lossy, guided, and leaky wave structures. To demonstrate the accuracy of the model, two plasmonic waveguides with space and time modulated graphene conductivity are analyzed and their interband and intraband transition between modes are thoroughly investigated. Using the developed analytical model, spatiotemporal modulation phenomena such as mode conversion, wave amplification and nonreciprocal response are explored and discussed for the studied structures.
Circulating TNF receptor levels are associated with estimated glomerular filtration rate even in healthy individuals with normal kidney function
Authors: Gohda Tomohito , Murakoshi Maki , Shibata Terumi , Suzuki Yusuke , Takemura Hiroyuki , Tsuchiya Koji , Okada Tomoki , Wakita Mitsuru , Horiuchi Yuki , Tabe Yoko , Kamei Nozomu
Published: March 2024

The association between serum tumor necrosis factor receptor (TNFRs: TNFR1, TNFR2) levels and estimated glomerular filtration rate (eGFR) observed in patients with diabetes has not been comprehensively tested in healthy subjects with normal kidney function. It also remains unclear whether TNFR levels differ by age and sex, and between healthy subjects and diabetics. We measured serum TNFR levels in 413 healthy subjects and 292 patients with type 2 diabetes. In healthy subjects, TNFR levels did not differ between men and women. Additionally, TNFR2, but not TNFR1, levels increased with age. In multivariate analysis, TNFR1 was associated only with cystatin C-based eGFR (eGFR-CysC), whereas TNFR2 was associated with systolic blood pressure in addition to eGFR-CysC. Both TNFRs were associated with lower eGFR (eGFR-Cys < 90 mL/min/1.73 m2) even after adjustment for relevant clinical factors. Upon combining healthy subjects and patients with diabetes, the presence of diabetes and elevated glycated hemoglobin level were significant factors in determining TNFR levels. TNFR levels were associated with eGFR-CysC, but were not affected by age and sex in healthy subjects with normal kidney function. TNFR levels in patients with diabetes appeared to be higher than in healthy subjects.
Prefeeding of Clarias gariepinus with Spirulina platensis counteracts petroleum hydrocarbons-induced hepato- and nephrotoxicity
Authors: Sayed Alaa El-Din H. , Khalil Nasser S. Abou , Alghriany Alshaimaa A. I. , Abdel-Ghaffar Sary Kh. , Hussein Asmaa A. A.
Published: March 2024

Petroleum aromatic hydrocarbons are considered one of the most dangerous aquatic pollutants due to their widespread across water bodies, persistence, and extension to the food chain. To our knowledge, there hasn’t been any research investigating the hepatorenoprotective effects of Spirulina platensis (SP) against toxicity induced by these environmental toxicants in fish. Thus, we decided to explore its potential safeguarding against benzene and toluene exposure in adult Clarias gariepinus. To achieve this objective, fish were divided into five groups (60 per group; 20 per replicate). The first group served as a control. The second and third groups were intoxicated with benzene and toluene at doses of 0.762 and 26.614 ng/L, respectively for 15 days. The fourth and fifth groups (SP + benzene and SP + toluene, respectively) were challenged with benzene and toluene as previously mentioned following dietary inclusion of SP at a dose of 5 g/kg diet for 30 days. The marked increase in liver metabolizing enzymes, glucose, total protein, albumin, globulin, albumin/globulin ratio, and creatinine confirmed the hepato- and nephrotoxic impacts of benzene and toluene. These outcomes were coupled with cytopathological affections and excessive collagen deposition. The incorporation of SP in ration formulation, on the contrary, restored the previously mentioned toxicological profile due to its antioxidant and cytoprotective attributes. Regardless of SP intervention, the renal tissues still displayed histo-architectural lesions, because of insufficient dose and timeframe. Additional research will be required to identify the ideal SP remediation regimen.
Associations between objectively measured overall and intensity-specific physical activity and phase angle in older adults
Authors: Chen Jiaren , Lai Ting-Fu , Lin Chien-Yu , Hsueh Ming-Chun , Park Jong-Hwan , Liao Yung
Published: March 2024

Phase angle (PhA) is an indicator of cellular health and is positively associated with overall physical activity (PA). However, varied associations between different intensities of PA and PhA by body segment in older populations remain unexplored. We investigated the associations between overall and different intensities of PA and upper-, lower-, and whole-body PhA in older adults. Overall exposure to light-intensity (LPA), moderate-intensity (MPA), and vigorous-intensity physical activity (VPA) was assessed using a triaxial accelerometer (GT3X + , ActiGraph). The outcome variables were upper-, lower-, and whole-body PhA measured using bioelectrical impedance analysis (MC-780MA, TANITA). Multiple linear regression helped examine the associations between the exposure and outcome variables after adjusting for age, gender, body mass index, and accelerometer wear time. A cross-sectional analysis involved 166 community-dwelling older participants (mean age = 72.1 ± 5.5 years; 78.3% women). Overall PA was associated with larger upper- (B: 0.057, 95% confidence interval [CI] 0.018–0.095) and whole-body PhA (B: 0.044, 95% CI 0.006–0.081). LPA was associated with larger upper-body PhA (B: 0.059, 95% CI 0.017–0.101), and MPA was associated with larger lower- (B: 0.273, 95% CI 0.128–0.419) and whole-body PhA (B: 0.141, 95% CI 0.002–0.280). VPA and PhA were not associated. Future interventions targeting PhA in older adults should consider the differential impact of PA intensity on various body segments of the PhA.
Association between general self-efficacy and health literacy among stroke survivors 1-year post-discharge: a cross-sectional study
Authors: Hess Engström Andrea , Flink Maria , Lindblom Sebastian , von Koch Lena , Ytterberg Charlotte
Published: March 2024

Stroke may affect physical functioning, cognition, and mental and social aspects of one’s life. Health literacy and self-efficacy are associated with positive health outcomes and are important factors for managing the diverse consequences of a stroke. However, there is very little literature on the association between health literacy and self-efficacy. This study aimed to investigate the association between health literacy and self-efficacy among stroke survivors 1 year after discharge from hospital. Participants in this cross-sectional study were patients diagnosed with a stroke, mainly a mild stroke, who were referred to rehabilitation in primary care after discharge from hospital in Sweden. Data was collected using questionnaires, performance-based tests, and medical records. Ordinal logistic regression was used to analyze the association between general self-efficacy and health literacy in adjusted models. The analysis revealed that higher levels of general self-efficacy and higher levels of performing activities of daily living were associated with higher levels of health literacy. Stroke survivors with higher general self-efficacy also report higher health literacy 1-year post-discharge from hospital. Future studies should focus on the pathways by which health literacy and general self-efficacy work among stroke survivors and in populations with low health literacy, severe stroke or significant cognitive impairments.
Research on the dynamic behavior of flexible drilling tools in ultrashort-radius radial horizontal wells
Authors: Lin Zhiqiang , Luo Min , Wang Jing , Xiu Tingting , Li Qiaozhen
Published: March 2024

A flexible drilling tool is a special drilling tool for ultrashort-radius radial horizontal wells. This tool is composed of many parts and has the characteristics of a multibody system. In this paper, a numerical method for the dynamic analysis of flexible drilling tools is proposed. The flexible drill tool is discretized into spatial beam elements, while the multilayer contact of the flexible drilling tool is represented by the multilayer dynamic gap element, and the dynamic model of the multibody system for the flexible drilling tool’s multilayer contact is established, considering the interaction force between the drill bit and the rock. The nonlinear dynamic equation is solved using the Newmark method and Newton–Raphson method. An analysis of the dynamic behavior of a flexible drilling tool is conducted. The results indicate that the flexible drilling tool experiences vortex formation due to the interaction between the flexible drilling pipe and the guide pipe, leading to increased friction and wear. This situation hinders safe drilling operations with flexible drilling tools. The collision force of the flexible drilling tool near the bottom of the hole is more severe than that of the other tool types, which may lead to failure of the connection.
Experimental and theoretical aspects of the growth of vertically aligned CNTs by CCVD on AZO substrate
Authors: Nánai Lilla , Németh Zoltán , Kaptay George , Hernadi Klara
Published: March 2024

An efficient and reproducible growth of vertically aligned carbon nanotubes by CCVD requires accurate and specific setting of the synthesis parameters and the properties of catalyst thin layers. In this work, the growth of vertically aligned carbon nanotubes onto AZO (= aluminum doped zinc oxide) glass substrate covered by Al2O3 and Fe-Co catalyst layer system is presented. Investigation of the effect of catalyst composition and synthesis temperature on CVD growth revealed the optimum condition of the synthesis. The analysis of as-prepared samples by SEM, TEM and Raman spectroscopy was carried out to prove the structure and quality of carbon deposit. Theoretical considerations have supported speculative ideas about the role of the support layer, the transformation of the catalyst layer in the presence of hydrogen gas and the growth mechanism of carbon nanotubes. The mechanism of CNT growth is modelled and the order of magnitude of experimentally observed vertical linear growth rate of CNT (several nm/s) is reproduced.
Collaborative optimization of depot location, capacity and rolling stock scheduling considering maintenance requirements
Authors: Zhong Qingwei , Yu Yingxue , Huang Yiru , Li Wenxin , Zhang Yongxiang , Yan Xu
Published: March 2024

Generally, when optimizing a rolling stock schedule, the locations of the depots, or places in the network where the composition changes and maintenance occurs, are assumed known. The locations where maintenance is performed naturally influence the quality of any resulting rolling stock schedules. In this paper, the problem of selecting new depot locations and their corresponding capacities is considered. A two-stage mixed integer programming approach for rolling stock scheduling with maintenance requirements is extended to account for depot selection. First, a conventional flow-based model is solved, ignoring maintenance requirements, to obtain a variety of rolling stock schedules with multiple depot locations and capacity options. Then, a maintenance feasible rolling stock schedule can be obtained by solving a series of assignment problems by using the schedules found in the first stage. The proposed methodology is tested on real-life instances, and the numerical experiments of different operational scenarios are discussed.
Removal of dead fish eggs by Asellus aquaticus as a potential biological control in aquaculture
Authors: Kucska Balázs , Ngọc Quyến Nguyễn , Ivánovics Bence , Staszny Ádám , Havasi Máté , Vranovics Károly , Griffitts Jeffrey Daniel , Varga Ádám , Urbányi Béla , Müller Tamás
Published: March 2024

The objective of the present experimental study was to gain a better understanding of the foraging activity of Asellus aquaticus during fish egg incubation. A. aquaticus were introduced into experimental setups of dead eggs, viable eggs and hatched larvae of zebrafish (Danio rerio), a commonly used model organism. The amount of A. aquaticus and the duration of their exposure to the eggs significantly affected the proportion of consumed dead eggs in each experimental cycle. A. aquaticus belongs to the group of aquatic detritivores, and no predatory behavior was observed during the experiments. These crustaceans could distinguish between the dead eggs and those containing living embryos. Furthermore, zebrafish larvae remained unharmed by A. aquaticus, even in the absence of alternative food source. These findings underscore the potential sanitary role of these crustaceans in natural waters and offer new perspectives on their possible use as biological control organisms in aquaculture hatcheries. Additionally, our results suggest a potential application of A. aquaticus in combating pathogens by reducing the growth substrates for bacteria and fungi.
Effects of psychological stress on the emission of volatile organic compounds from the skin
Authors: Lucchi Géraldine , Crépin Marine , Chambaron Stéphanie , Peltier Caroline , Gilbert Laura , Guéré Christelle , Vié Katell
Published: March 2024

Thirty-five women were included in a clinical study to characterize the volatile organic compounds (VOCs) emitted by the skin during exposure to psychological stress. An original silicon-based polymeric phase was used for VOC sampling on the forehead before and after stress induction. Cognitive stress was induced using specialized software that included a chronometer for semantic and arithmetic tasks. Assessment of stress was monitored using a State-trait anxiety inventory questionnaire, analysis of participants’ verbal expressions and clinical measurements. Identification and relative quantification of VOCs were performed by gas chromatography-mass spectrometry. Stress induction was validated by a significant increase in state-anxiety as indicated by the questionnaire, modifications in electrodermal activity measurements and the expression of stress verbatims. In parallel, a sebum production increase and a skin pH decrease were observed. A total of 198 VOCs with different potential sources were identified. They were categorized in 5 groups: probable cosmetic composition, VOCs produced by the body or its microbiota, environmental origin, and dietary intake. In our qualitative statistical approach, three VOCs were found to be correlated with stress induction and 14 compounds showed significance in the paired Wilcoxon test. Fatty-acyls derived from lipids were predominantly identified as well as ethylbenzenes.
Research on inhibitory effect of mixed suppressants CaCO3, KCl, and K2CO3 on coal dust explosion pressure
Authors: Liu Tianqi , Liu Kenan
Published: March 2024

To discuss the inhibitory effect of micrometer scale coal dust explosion pressure, three types of explosion suppressants are selected for mixed explosion suppression. The results indicate that the coal dust explosion process includes three stages: accelerated and decelerated energy release, as well as energy dissipation. When using explosive suppressants, K2CO3 has the greatest inhibitory effect on coal dust explosion, followed by KCl, and CaCO3 has the smallest effect. The K2O, K2O2, and KOH generated by the thermal decomposition of K2CO3 can also block the heat transfer of coal dust, playing a good role in suppressing explosions. The explosion suppression effect of mixing CaCO3 and K2CO3 is better than that of mixing CaCO3 and KCl, and is worse than the explosion suppression effect of using K2CO3 alone. The synergistic effect of KCl and K2CO3 mixed explosion suppression makes the suppression effect better than using K2CO3 alone. This is because KCl generates K2O during pyrolysis, promoting the dynamic equilibrium of K2CO3 explosion suppression process. This makes mixed explosion suppression more worthy of attention and adoption when considering purchase costs.
Applications of NMR in Drug Substance and Drug Product Development
Authors: Elipe Maria Victoria Silva
Published: March 2024

Drug substances and drug products are pharmaceutical materials that require complete characterization during their development process and in preparation of their submission to regulatory filing for approval for human consumption. Nuclear magnetic resonance (NMR) is one of the most informative analytical techniques that characterizes organic materials, which are used as building blocks towards the synthesis of drug substances and common components of drug products during the development stages in the pharmaceutical industry. In this chapter, we describe the applications of NMR during the development process of drug substances and drug products from small molecule drugs. In the area of drug substance development, the topics selected are structure elucidation of drug substances and materials related to their production, in-process impurities, and impurities from stability studies, quantitation of drug substances and related compounds, relative configuration of drug substances, reaction monitoring during process development, and solid-state NMR (SSNMR) characterization of drug substances. In the case of drug product development, the topics selected are the structure elucidation of impurities during stability studies of formulated drug substances, SSNMR of drug products, and quantitation of drug substances in the formulated drug products. Examples from the literature are used to describe those applications.
The Application of Magnetic Resonance to Testing Counterfeit, Falsified, and Substandard Medicines
Authors: McCudden A. , Embrey K.
Published: March 2024

Counterfeit, falsified, and substandard medicines constitute a major public health problem resulting in hundreds of thousands of preventable deaths each year. Authentication, forensic, and compositional analyses of samples suspected to be counterfeit play a crucial role in combating this illegal and deadly trade. Because of the wide and often unexpected range of ingredients found in counterfeit pharmaceuticals their characterization presents a significant technical challenge for analytical scientists. Although seldom used in quality control laboratories, magnetic resonance (MR) techniques are ideally suited to the analysis of suspect samples of pharmaceuticals. The ability of MR techniques such as nuclear magnetic resonance (NMR) spectroscopy to act as universal detection methods means they can be employed in the identification and quantification of a wide range of organic compounds. Even if part of complex pharmaceutical formulations, whether used in isolation or in concert with orthogonal analyses, magnetic resonance techniques are a powerful weapon in the fight against fakes.