bluuebunny/crossref_metadata_2025 huggingface dataset:
Testing for protonitazene in human hair using LC–MS-MS
Authors: Kintz Pascal , Ameline Alice , Gheddar Laurie , Pichini Simona , Mazoyer Cédric , Teston Katy , Aknouche Frédéric , Maruejouls Christophe
Published: June 2024

Protonitazene is a synthetic benzimidazole opioid of the nitazenes class, developed in the 1950s as an effective analgesic, but never released on the market due to severe side effects and possible dependence. Despite its increasing use as a new psychoactive substance starting in 2019, its detection in human hair of intoxicated and deceased consumers has never been reported. We present the development and validation of a specific procedure to identify protonitazene in hair by liquid chromatography with tandem mass spectrometry. Drugs were incubated overnight at 40°C in 1 mL borate buffer, pH 9.5 with 20 mg pulverized hair and 1 ng/mg fentanyl-d5 used as internal standard. Drugs were then extracted with a mixture of organic solvents. The chromatographic separation was performed using an HSS C18 column with a 15-min gradient elution. Linearity was verified from 1 to 100 pg/mg. The limit of detection was estimated at 0.1 pg/mg. No interference was noted from a large panel of natural and synthetic opioids, fentanyl derivatives, or other new synthetic opioids. Protonitazene was identified at 70 and >7600 pg/mg in the whole head hair specimens of two male subjects deceased from an acute drug overdose in jail. Protonitazene was also identified at 14 and 54 pg/mg in two living co-prisoners. As nitazenes represent a growing threat to public health in various parts of the world, this method was developed in response to the challenges posed by the identification of this class of substances.
Passive seismic monitoring of an injection-production process in an oilfield using reverse time imaging
Authors: Yuan Runbi , Zou Zhihui , Xu Song , Kuang Wenhuan
Published: June 2024

Monitoring underground fluid migration caused by injection/production processes is crucial for guiding petroleum exploitation in mature oilfields and ultimately enhancing petroleum production. In this paper, we propose a time-lapse reverse time imaging (RTI) to dynamically monitor the injection/production processes within oilfield. By using RTI to track microseimicities at different time periods, we can analyze the relationship between injection/production activities and the spatiotemporal changes in microseismic distribution. The inferred relationship enables the time-lapse RTI to infer fluid migration patterns within oil reservoirs. To assess the accuracy and spatiotemporal resolution of the time-lapse RTI, we conducted numerical experiments to evaluate the imaging quality under different microseismic distribution scenarios. In addition, we assessed the method's stability under low signal-to-noise ratio conditions. Numerical results indicate that the time-lapse RTI can effectively distinguish the spatiotemporal variations of seismic swarms at depths of 0.5 kilometers within the target layer, even in the presence of strong noise. Practical applications show a significant correlation between changes in swarm distribution surrounding reservoirs and fluctuations in oil production. Using time-lapse RTI enables real-time monitoring of oilfield injection/production processes, thereby offering valuable insights for optimizing oilfield development and fostering future increases in petroleum production.
Traffic control on the toll road
Authors: Hao Kaiyuan , Nündel Kerstin
Published: June 2024

In B cells, TRAF3 plays a central role in regulating the B cell receptor and the toll-like receptor signaling cascade by inhibiting Syk phospohorylation as well as its localization to the Myddosome.
Eosinophil-derived extracellular vesicles: isolation and classification techniques and implications for disease pathophysiology
Authors: Rodrigo-Muñoz José Manuel , Gil-Martínez Marta , Naharro-González Sara , del Pozo Victoria
Published: June 2024

Eosinophils are leukocytes characterized by their ability to release granule content that is highly rich in enzymes and proteins. Besides the antihelminthic, bactericidal, and antiviral properties of eosinophils and their secretory granules, these also play a prominent role in the pathophysiology of diseases such as asthma, eosinophilic esophagitis, and other hypereosinophilic conditions by causing tissue damage and airway hyperresponsiveness. Although this cell was first recognized mainly for its capacity to release granule content, nowadays other capabilities such as cytokine secretion have been linked to its physiology, and research has found that eosinophils are not only involved in innate immunity, but also as orchestrators of immune responses. Nearly 10 yr ago, eosinophil-derived extracellular vesicles (EVs) were first described; since then, the EV field has grown exponentially, revealing their vital roles in intracellular communication. In this review, we synthesize current knowledge on eosinophil-derived EVs, beginning with a description of what they are and what makes them important regulators of disease, followed by an account of the methodologies used to isolate and characterize EVs. We also summarize current understanding of eosinophil-derived vesicles functionality, especially in asthma, the disease in which eosinophil-derived EVs have been most widely studied, describing how they modulate the role of eosinophils themselves (through autocrine signaling) and the way they affect airway structural cells and airway remodeling. Deeper understanding of this cell type could lead to novel research in eosinophil biology, its role in other diseases, and possible use of eosinophil-derived EVs as therapeutic targets.
BATF-dependent Th17 cells act through the IL-23R pathway to promote prostate adenocarcinoma initiation and progression
Authors: Liu Sen , Rivero Seleste L , Zhang Bing , Shen Keyi , Li Zixuan , Niu Tianhua , Rowan Brian G , Jazwinski S Michal , Abdel-Mageed Asim B , Steele Chad , Wang Alun R , Sartor Oliver , Zhang Qiuyang
Published: June 2024

Background

The role of Th17 cells in prostate cancer is not fully understood. The transcription factor BATF controls the differentiation of Th17 cells. Mice deficient in Batf do not produce Th17 cells.

Methods

In this study, we aimed to characterize the role of Batf-dependent Th17 cells in prostate cancer by crossbreeding Batf knockout mice with mice conditionally mutant for Pten.

Results

We found that Batf knockout mice had changes in the morphology of prostate epithelial cells compared with normal mice, and Batf knockout mice deficient in Pten (called Batf-) had smaller prostate size and developed fewer invasive prostate adenocarcinomas than Pten-deficient mice with Batf expression (called Batf+). The prostate tumors in Batf- mice showed reduced proliferation, increased apoptosis, decreased angiogenesis and inflammatory cell infiltration, and activation of nuclear factor–κB signaling. Moreover, Batf- mice showed significantly reduced interleukin 23 (IL-23)-IL-23R signaling. In the prostate stroma of Batf- mice, IL-23R–positive cells were decreased considerably compared with Batf+ mice. Splenocytes and prostate tissues from Batf- mice cultured under Th17 differentiation conditions expressed reduced IL-23/IL-23R than cultured cells from Batf+ mice. Anti–IL-23p19 antibody treatment of Pten-deficient mice reduced prostate tumors and angiogenesis compared with control immunoglobulin G–treated mice. In human prostate tumors, BATF messenger RNA level was positively correlated with IL-23A and IL-23R but not RORC.

Conclusion

Our novel findings underscore the crucial role of IL-23-IL-23R signaling in mediating the function of Batf-dependent Th17 cells, thereby promoting prostate cancer initiation and progression. This finding highlights the BATF–IL-23R axis as a promising target for the development of innovative strategies for prostate cancer prevention and treatment.
Multi-objective analysis of solid-state joints: Effect of tool pin shoulder clearance on thick dissimilar aluminum plates
Authors: Mishra Deepika , Prasad Ravi Shankar , Kumar Sudhir
Published: June 2024

Friction stir welding is a well-established technique developed extensively over the past two decades for various applications. This study investigates the effect of repositioning the tool pin shoulder (0.18 mm) above the surface of a 12 mm thick dissimilar aluminum alloy (AA6063-AA5083) on tensile strength, welding temperature, and micro-hardness. Trials were conducted according to the L9 Taguchi method and further simulated using ABAQUS software. The input parameters spindle speed, tool pin length, and traversing speed were each tested at three levels. The impact of these parameters on weld quality was analyzed using ANOVA. Optimization of the process to achieve the desired temperature and tensile strength was carried out using grey relational analysis for both experimental and simulated results. Mathematical models were generated using the multi-variable regression method and the response surface method (RSM). Predicted data from the RSM model were compared to experimental outcomes, revealing a maximum deviation of 8.69% for temperature and 5.17% for tensile strength. Furthermore, the study demonstrated that ABAQUS accurately simulates the friction stir welding process with an accuracy of up to 93.71%.
Intervention Effects in Mandarin Chinese—An Experimental Study
Authors: Jin Dawei , Yan Hanbo
Published: June 2024

This paper presents a formal judgment study of Mandarin intervention effects, that is, structures containing a wh-phrase c-commanded by a focus-sensitive or a quantificational expression. There has been significant disagreement in the literature regarding which type of wh-phrases gives rise to intervention, as well as which one among the c-commanding scopal operators is an intervener. There are competing empirical claims in the literature, which have to this day not been subject to experimental evaluation. The results of our study show that wh-nominals and wh-adverbials exhibit a similar pattern of degraded acceptability. Our results further show a clear distinction between why and other wh-phrases, favoring Ko’s (2005) idea that a separate, why-induced scope effect is disentangled from the garden-variety case of wh-intervention.
Overcoming Challenges for Non-US International Medical Graduates in Pediatric Infectious Diseases
Authors: Teoh Zheyi , Erdem Guliz , Tomatis-Souverbielle Cristina , Cruz-Vidal Diego A , Rueda Maria S , Santos Roberto P , Olarte Liset
Published: June 2024

International medical graduates (IMGs) in pediatric infectious diseases face unique and complex challenges related to their immigration status. This Perspective provides a review of challenges impacting non-US IMG trainees and early-career faculty, and how the infectious diseases community can respond.
Effectiveness of nonpharmaceutical policy interventions in reducing population mobility during the COVID-19 pandemic
Authors: Klingwort Jonas , Burger Joep , van den Brakel Jan
Published: June 2024

Nonpharmaceutical policy interventions (NPIs) are intended to reduce population mobility in mitigating the spread of COVID-19. This paper evaluates their effect on population mobility during the COVID-19 pandemic. State space models are applied to estimate the time-varying effects of NPI stringency on weekly pedestrian counts from location-based sensors installed before the pandemic. Different models are developed that evaluate compliance with NPIs over time, identify the most effective NPI, and identify regional differences. An efficient parsimonious alternative is proposed for the multivariate Seemingly Unrelated Time Series Equation model if full covariance matrices are of full rank. Kalman filter estimates of the regression coefficients show that NPI stringency initially had a negative effect on population mobility. The effect weakened during the pandemic, suggesting a reduced willingness to comply with regulations. Four of nine NPIs were identified as the most effective. The multivariate model confirmed the findings across federal states. This paper highlights how combining new data sources, routinely collected administrative data, and sound methodology fosters modern policy evaluation.
Shakespeare Machine: New AI-Based Technologies for Textual Analysis
Authors: Ehrett Carl , Ghita Lucian , Ranwala Dillon , Menezes Alison
Published: June 2024

This article demonstrates a method using tools from the field of Natural Language Processing (NLP) to aid in analyzing theatrical texts and similar works. The method deploys pre-trained large language model neural networks to gather metadata for a text that is amenable to downstream statistical analyses surfacing patterns of interest in character dialogue. We specifically focus on Shakespeare’s works, collecting metadata in the form of sentiment and emotion scores for each line of his plays. In addition to sentiment and emotion scores produced by NLP models, we also directly gather metadata such as genre, line length, and character gender. We show how these metadata may be used to illuminate a number of interesting patterns in Shakespearean character which may be difficult to detect from a direct reading of the texts. We use these metadata to expose statistically significant relationships in Shakespeare between character gender and the emotional content of that character’s dialogue, controlling for genre. We also present here the publicly available dataset that we have compiled to perform these analyses. The data collects text from Shakespeare’s plays along with a variety of metadata useful for this and other forms of analysis of Shakespeare’s works. The methodology demonstrated here may be extended to other varieties of metadata provided by large NLP models.
Novel Insights Into the Architecture of Macro and Microstructures in Cattle Ossa Cordis
Authors: Alsafy Mohamed A M , El-Gendy Samir A A , Atkinson Brian , Sturrock Craig J , Kamal Basma M , Alibhai Aziza , Abd-Elhafeez Hanan H , Soliman Soha , Rashwan Ahmed M , Roshdy Karam , Rutland Catrin S
Published: June 2024

Ossa cordis, bones located within the heart trigones, are often classified as heterotopic or ectopic bones. Despite their high prevalence in cattle and some other bovids, little is known about their structure or development. Scanning electron microscopy, X-ray microtomography, gross dissections, and measurements showed the anatomical locations, prevalence, shapes, and measurements of the cardiac bones in both Egyptian Baladi cattle and Holstein-Friesians. All cattle (n = 12) had an Ossa cordis dextrum (average = 50.70 × 20.91 × 5.40 mm). Additionally, 80% Egyptian Baladi and 57% Holstein-Friesian had a smaller Ossa cordis sinistrum (average = 24.94 × 12.75 × 4.12 mm). Egyptian Baladi Ossa cordis were smaller than observed in Holstein-Friesians. Energy-dispersive X-ray analysis showed the elemental constitution (carbon, oxygen, calcium, nitrogen, phosphorus, sodium, and magnesium) of Ossa cordis and Cartilago cordis. These imaging techniques, plus four histological stains (hematoxylin and eosin, Crossman's trichrome, Alcian blue with Van Gieson, and Sirius Red) and microscopy, demonstrated osteoblasts, osteocytes, osteoclasts, astrocytes, blood vessels, bone marrow, lamellar and woven bone, cortical bone, trabeculations with pores and canaliculi, and fibrous components including collagen in the Ossa cordis dextrum and sinistrum. Hyaline cartilage and fibrocartilage (chondrocytes and cartilage matrix) were found within and surrounding the Ossa cordis. These findings were additionally compared against other cattle breeds and species.
Schoenberg as Analyst
Authors: Haralambous Nicholas
Published: June 2024

Schoenberg’s understanding of the value and function of music analysis is difficult to pin down. As such, the secondary literature has tended to focus on the technical aspects of his extant analyses. While salutary in many respects, this preoccupation risks divesting Schoenbergian analysis of its underlying concerns. This essay therefore explores the wider network of ideas in which Schoenberg’s analytical practice is grounded. I show his understanding of analysis to be delineated by three contrasting perspectives. The tensions that emerge between these perspectives may be reconciled within a single epistemological framework that outlines the prospects for and limitations of analytical enquiry. This model of analysis is illustrated by a case study of Schoenberg’s 1932 radio discussion of ‘Seraphita’, Op. 22 No. 1. In these ways, the article not only expands and clarifies our understanding of Schoenberg’s analytical thinking, but also poses provocative challenges for the analysis of his music.
Measuring the Efficiency of Purging by non-random Mating in Human Populations
Authors: Laurent Romain , Gineau Laure , Utge José , Lafosse Sophie , Phoeung Chan Leakhena , Hegay Tatyana , Olaso Robert , Boland Anne , Deleuze Jean-François , Toupance Bruno , Heyer Evelyne , Leutenegger Anne-Louise , Chaix Raphaëlle
Published: June 2024

Human populations harbor a high concentration of deleterious genetic variants. Here, we tested the hypothesis that non-random mating practices affect the distribution of these variants, through exposure in the homozygous state, leading to their purging from the population gene pool. To do so, we produced whole-genome sequencing data for two pairs of Asian populations exhibiting different alliance rules and rates of inbreeding, but with similar effective population sizes. The results show that populations with higher rates of inbred matings do not purge deleterious variants more efficiently. Purging therefore has a low efficiency in human populations, and different mating practices lead to a similar mutational load.
Disturbance in cerebral blood microcirculation and hypoxic-ischemic microenvironment are associated with the development of brain metastasis
Authors: Roesler Jenny , Spitzer Daniel , Jia Xiaoxiong , Aasen Synnøve Nymark , Sommer Kathleen , Roller Bastian , Olshausen Niels , Hebach Nils R , Albinger Nawid , Ullrich Evelyn , Zhu Ling , Wang Fan , Macas Jadranka , Forster Marie-Therese , Steinbach Joachim P , Sevenich Lisa , Devraj Kavi , Thorsen Frits , Karreman Matthia A , Plate Karl H , Reiss Yvonne , Harter Patrick N
Published: June 2024

Background

Brain metastases (BM) constitute an increasing challenge in oncology due to their impact on neurological function, limited treatment options, and poor prognosis. BM occurs through extravasation of circulating tumor cells across the blood-brain barrier. However, the extravasation processes are still poorly understood. We here propose a brain colonization process which mimics infarction-like microenvironmental reactions, that are dependent on Angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF).

Methods

In this study, intracardiac BM models were used, and cerebral blood microcirculation was monitored by 2-photon microscopy through a cranial window. BM formation was observed using cranial magnetic resonance, bioluminescent imaging, and postmortem autopsy. Ang-2/VEGF targeting strategies and Ang-2 gain-of-function (GOF) mice were employed to interfere with BM formation. In addition, vascular and stromal factors as well as clinical outcomes were analyzed in BM patients.

Results

Blood vessel occlusions by cancer cells were detected, accompanied by significant disturbances of cerebral blood microcirculation, and focal stroke-like histological signs. Cerebral endothelial cells showed an elevated Ang-2 expression both in mouse and human BM. Ang-2 GOF resulted in an increased BM burden. Combined anti-Ang-2/anti-VEGF therapy led to a decrease in brain metastasis size and number. Ang-2 expression in tumor vessels of established human BM negatively correlated with survival.

Conclusions

Our observations revealed a relationship between disturbance of cerebral blood microcirculation and brain metastasis formation. This suggests that vessel occlusion by tumor cells facilitates brain metastatic extravasation and seeding, while combined inhibition of microenvironmental effects of Ang-2 and VEGF prevents the outgrowth of macrometastases.
Links between Calcite Kimberlite, Aillikite and Carbonatite in West Greenland: Numeric Modeling of Compositional Relationships
Authors: Pilbeam L H , Nielsen T F D , Waight T , Tappe S
Published: June 2024

Textural, mineralogical and mineral compositional observations in a suite of Neoproterozoic aillikite and calcite kimberlite dykes from southern West Greenland point to consistent variations in melt major element compositions amongst these silica-undersaturated magma types. The aillikites have notably higher bulk SiO2/CO2, H2O/CO2 and K2O compared to calcite kimberlite. Bulk rock arrays, together with field and petrographic observations, emphasize that flow sorting of olivine and other crystalline phases during magma emplacement is important in controlling the compositions of individual samples from these ultramafic dykes. Flow sorting together with variable overall proportions of entrained lithospheric mantle material result in scatter on element–element plots, which makes the interpretation of regional scale major and trace element geochemical datasets difficult. We argue that a significant proportion of the regional Ni–MgO variation in the ultramafic dyke suite of SW Greenland is due to variation in the proportion of an entrained refractory lithospheric mantle component. Therefore, ratios of elements to MgO can be used as proxies for melt compositions. Ratios of SiO2, TiO2, Al2O3, FeO and K2O over MgO are systematically higher, and CO2/MgO lower, in aillikites compared to calcite kimberlites. The trace element patterns of the calcite kimberlite and aillikite dykes show strong similarities in incompatible element concentrations, resulting in overlapping ratios for the highly to moderately incompatible elements. However, differences in Zr-Hf concentrations between rock types imply differences in mantle source mineralogy. Guided by our observations, we present mixing models that demonstrate that partial flux-melting of phlogopite–ilmenite metasomes within the cratonic mantle lithosphere is capable of produce the geochemical characteristics of aillikites and mela-aillikites in West Greenland. Fusion of cratonic metasomes was initiated by infiltrating asthenosphere-derived carbonatitic melts previously identified as the parental liquids to calcite kimberlite.
The calcium-dependent protein kinase CPK16 regulates hypoxia-induced ROS production by phosphorylating the NADPH oxidase RBOHD in Arabidopsis
Authors: Yu Wei-Wei , Chen Qin-Fang , Liao Ke , Zhou De-Mian , Yang Yi-Cong , He Miao , Yu Lu-Jun , Guo De-Ying , Xiao Shi , Xie Ruo-Han , Zhou Ying
Published: June 2024

Reactive oxygen species (ROS) production is a key event in modulating plant responses to hypoxia and post-hypoxia reoxygenation. However, the molecular mechanism by which hypoxia-associated ROS homeostasis is controlled remains largely unknown. Here, we showed that the calcium-dependent protein kinase CPK16 regulates plant hypoxia tolerance by phosphorylating the plasma membrane-anchored NADPH oxidase respiratory burst oxidase homolog D (RBOHD) to regulate ROS production in Arabidopsis (Arabidopsis thaliana). In response to hypoxia or reoxygenation, CPK16 was activated through phosphorylation of its Ser274 residue. The cpk16 knockout mutant displayed enhanced hypoxia tolerance, whereas CPK16-overexpressing (CPK16-OE) lines showed increased sensitivity to hypoxic stress. In agreement with these observations, hypoxia and reoxygenation both induced ROS accumulation in the rosettes of CPK16-OEs more strongly than in the rosettes of the cpk16-1 mutant or the wild type. Moreover, CPK16 interacted with and phosphorylated the N-terminus of RBOHD at 4 serine residues (Ser133, Ser148, Ser163, and Ser347) that were necessary for hypoxia- and reoxygenation-induced ROS accumulation. Furthermore, the hypoxia-tolerant phenotype of cpk16-1 was fully abolished in the cpk16 rbohd double mutant. Thus, we have uncovered a regulatory mechanism by which the CPK16–RBOHD module shapes the ROS production during hypoxia and reoxygenation in Arabidopsis.
A cellulose synthesis inhibitor affects cellulose synthase complex secretion and cortical microtubule dynamics
Authors: Renou Julien , Li Deqiang , Lu Juan , Zhang Baocai , Gineau Emilie , Ye Yajin , Shi Jianmin , Voxeur Aline , Akary Elodie , Marmagne Anne , Gonneau Martine , Uyttewaal Magalie , Höfte Herman , Zhao Yang , Vernhettes Samantha
Published: June 2024

P4B (2-phenyl-1-[4-(6-(piperidin-1-yl) pyridazin-3-yl) piperazin-1-yl] butan-1-one) is a novel cellulose biosynthesis inhibitor (CBI) discovered in a screen for molecules to identify inhibitors of Arabidopsis (Arabidopsis thaliana) seedling growth. Growth and cellulose synthesis inhibition by P4B were greatly reduced in a novel mutant for the cellulose synthase catalytic subunit gene CESA3 (cesa3pbr1). Cross-tolerance to P4B was also observed for isoxaben-resistant (ixr) cesa3 mutants ixr1-1 and ixr1-2. P4B has an original mode of action as compared with most other CBIs. Indeed, short-term treatments with P4B did not affect the velocity of cellulose synthase complexes (CSCs) but led to a decrease in CSC density in the plasma membrane without affecting their accumulation in microtubule-associated compartments. This was observed in the wild type but not in a cesa3pbr1 background. This reduced density correlated with a reduced delivery rate of CSCs to the plasma membrane but also with changes in cortical microtubule dynamics and orientation. At longer timescales, however, the responses to P4B treatments resembled those to other CBIs, including the inhibition of CSC motility, reduced growth anisotropy, interference with the assembly of an extensible wall, pectin demethylesterification, and ectopic lignin and callose accumulation. Together, the data suggest that P4B either directly targets CESA3 or affects another cellular function related to CSC plasma membrane delivery and/or microtubule dynamics that is bypassed specifically by mutations in CESA3.
Stomatal CO2 responses at sub- and above-ambient CO2 levels employ different pathways in Arabidopsis
Authors: Koolmeister Kaspar , Merilo Ebe , Hõrak Hanna , Kollist Hannes
Published: June 2024

Stomatal pores that control plant CO2 uptake and water loss affect global carbon and water cycles. In the era of increasing atmospheric CO2 levels and vapor pressure deficit (VPD), it is essential to understand how these stimuli affect stomatal behavior. Whether stomatal responses to sub-ambient and above-ambient CO2 levels are governed by the same regulators and depend on VPD remains unknown. We studied stomatal conductance responses in Arabidopsis (Arabidopsis thaliana) stomatal signaling mutants under conditions where CO2 levels were either increased from sub-ambient to ambient (400 ppm) or from ambient to above-ambient levels under normal or elevated VPD. We found that guard cell signaling components involved in CO2-induced stomatal closure have different roles in the sub-ambient and above-ambient CO2 levels. The CO2-specific regulators prominently affected sub-ambient CO2 responses, whereas the lack of guard cell slow-type anion channel SLOW ANION CHANNEL-ASSOCIATED 1 (SLAC1) more strongly affected the speed of above-ambient CO2-induced stomatal closure. Elevated VPD caused lower stomatal conductance in all studied genotypes and CO2 transitions, as well as faster CO2-responsiveness in some studied genotypes and CO2 transitions. Our results highlight the importance of experimental setups in interpreting stomatal CO2-responsiveness, as stomatal movements under different CO2 concentration ranges are controlled by distinct mechanisms. Elevated CO2 and VPD responses may also interact. Hence, multi-factor treatments are needed to understand how plants integrate different environmental signals and translate them into stomatal responses.
Relationship between human serum metabolites and angina pectoris: a Mendelian randomization study
Authors: Xiong Jian , Liao Ying , Yang Liyuan , Wei Ying , Li Dehua , Zhao Yi , Zheng Qianhua , Qi Wenchuan , Liang Fanrong
Published: June 2024

Purpose

We aimed to explore the causal relationship between human serum metabolites and angina pectoris.

Methods

This study used two-sample Mendelian randomization (MR) analysis to assess the association between 486 serum metabolites and angina pectoris. The analytical methods employed to reduce study bias included inverse variance weighted, MR-Egger, and weighted median method. A comprehensive sensitivity analysis was performed using the leave-one-out method, while instrumental variable pleiotropy was tested with MR-Pleiotropy RESidual Sum and Outlier. Metabolic pathways of angina-associated metabolites were analysed on the MetaboAnalyst metabolomics analysis tool platform.

Results

In this study, 42 serum metabolites were found to be strongly associated with angina pectoris. They mainly belonged to seven groups: amino acids, carbohydrates, cofactors and vitamins, lipids, nucleotides, unknown metabolites, and exogenous substances. Pipecolate posed the highest risk for the development of angina pectoris among the 42 serum metabolites. The main metabolic pathways associated with angina pectoris were glycine, serine, threonine metabolism, primary bile acid biosynthesis, and caffeine metabolism.

Conclusion

We identified 25 high-risk and 17 protective human serum metabolites associated with angina pectoris. Their associated major metabolic pathways were also determined. The serum metabolite pipecolate was significantly and positively correlated with the risk of angina pectoris. This finding may serve as a valuable reference for testing serum markers associated with angina pectoris.
CPT, Majorana Fermions, and Particle Physics Beyond the Standard Model
Authors: Hikasa Ken-ichi
Published: June 2024

After reviewing charge conjugation and the CPT theorem, we define Majorana fermions and clarify the relationship between the Majorana, Weyl, and Dirac fields. The appearance of Majorana fermions in various scenarios of physics beyond the Standard Model is discussed, including neutrino masses, the baryon asymmetry of the universe, grand unified theories, and supersymmetry.
Inflation Levels and (In)Attention
Authors: Bracha Anat , Tang Jenny
Published: June 2024

Inflation expectations are key determinants of economic activity and are central to the current policy debate about whether inflation expectations will remain anchored in the face of recent pandemic-related increases in inflation. This article explores evidence of inattention by constructing two novel and direct measures of consumers’ inattention, and documents greater attention when inflation is high. This relationship can explain a substantial portion of the flattening of the Phillips curve and also suggests the possibility of upward attention-price spirals.
Curcumin protects against cadmium-induced germ cell death in the testis of rats
Authors: Li Yamin , Yang Lu , Su Ping , Chen Na
Published: June 2024

Introduction

Cadmium (Cd) has been shown to disrupt the reproductive system. In this study, we evaluated the protective effects of Curcumin (Cur) against Cd-induced reproductive toxicity.

Methods

Exploring the role of Cur in Cd-treated rat models.

Results

The study demonstrated that Cd treatment impaired the seminiferous epithelium, leading to increased apoptosis of germ cells. Interestingly, pretreatment with Cur ameliorated the histological damage and decreased the germ cell apoptosis induced by Cd. Furthermore, after Cd exposure, B-cell lymphoma-2 expression was significantly decreased while Bax expression was increased. Pretreatment of rats with Cur protected against germ cell apoptosis by improving the expression of B-cell lymphoma-2 and reducing Bax. Additionally, Cd treatment increased reactive oxygen species, resulting in a decrease in antioxidant enzymes. However, pretreatment of rats with Cur followed by Cd administration led to a substantial decrease in reactive oxygen species levels and increased activities of antioxidant enzymes. Ultrastructural investigations revealed that damage to the mitochondrial structure was significantly ameliorated by Cur pretreatment in Cd-treated rats. Notably, Cur significantly activated the peroxisome proliferator-activated receptor gamma coactivator 1a/Sirtuins-3 signaling pathway.

Conclusions

Overall, our data suggest that Cd induces germ cell apoptosis through mitochondrial-induced oxidative stress, but Cur pretreatment offers strong protection against Cd-induced reproductive toxicity.
Impaired cathepsin D in retinal pigment epithelium cells mediates Stargardt disease pathogenesis
Authors: Ng Eunice Sze Yin , Hu Jane , Jiang Zhichun , Radu Roxana A.
Published: June 2024

Recessive Stargardt disease (STGD1) is an inherited juvenile maculopathy caused by mutations in the ABCA4 gene, for which there is no suitable treatment. Loss of functional ABCA4 in the retinal pigment epithelium (RPE) alone, without contribution from photoreceptor cells, was shown to induce STGD1 pathology. Here, we identified cathepsin D (CatD), the primary RPE lysosomal protease, as a key molecular player contributing to endo‐lysosomal dysfunction in STGD1 using a newly developed “disease‐in‐a‐dish” RPE model from confirmed STGD1 patients. Induced pluripotent stem cell (iPSC)‐derived RPE originating from three STGD1 patients exhibited elevated lysosomal pH, as previously reported in Abca4−/− mice. CatD protein maturation and activity were impaired in RPE from STGD1 patients and Abca4−/− mice. Consequently, STGD1 RPE cells have reduced photoreceptor outer segment degradation and abnormal accumulation of α‐synuclein, the natural substrate of CatD. Furthermore, dysfunctional ABCA4 in STGD1 RPE cells results in intracellular accumulation of autofluorescent material and phosphatidylethanolamine (PE). The altered distribution of PE associated with the internal membranes of STGD1 RPE cells presumably compromises LC3‐associated phagocytosis, contributing to delayed endo‐lysosomal degradation activity. Drug‐mediated re‐acidification of lysosomes in the RPE of STGD1 restores CatD functional activity and reduces the accumulation of immature CatD protein loads. This preclinical study validates the contribution of CatD deficiencies to STGD1 pathology and provides evidence for an efficacious therapeutic approach targeting RPE cells. Our findings support a cell‐autonomous RPE‐driven pathology, informing future research aimed at targeting RPE cells to treat ABCA4‐mediated retinopathies.
U.S. Medical School Participation in Nationally Funded Biomedical Research: A New Accounting of NIH Award Dollars
Authors: Geboy Alexander G. , Dandar Valerie M. , Dutterer Jordan , Brandenburg Katherine , Alexander Hershel
Published: June 2024

To better understand the amount of National Institutes of Health (NIH) funding received by U.S. medical schools with Liaison Committee on Medical Education–accredited medical education programs, the Association of American Medical Colleges (AAMC) developed a new methodology that crosswalks faculty NIH grants with medical schools and their affiliated organizations (e.g., teaching hospitals). This approach offers a more comprehensive and methodologically transparent accounting of NIH extramural funding to academic medicine than existing processes.

The AAMC Crosswalk utilized publicly available grants data from the NIH and resources unique to the AAMC, such as the Faculty Roster and Council of Teaching Hospitals and Health Systems records. Using a multistep algorithm, the AAMC Crosswalk linked individual faculty with NIH grants, their organizations, and partner medical schools, aggregated at the level of the medical school and its affiliated organizations for fiscal year (FY) 2017–2021.

The AAMC Crosswalk attributed, on average, $3.7 billion more per year in NIH funding to U.S. medical schools, representing a 24% increase compared to the NIH and Blue Ridge Institute for Medical Research (BRIMR) methodologies. In FY 2021, the AAMC Crosswalk attributed 60% of NIH funding to U.S. medical schools compared with 47% by NIH and 50% by BRIMR. An exploration of limitations showed that no medical school affiliations were missed by the AAMC Crosswalk among 90 randomly sampled organizations, and medical school affiliations for 30 randomly sampled principal investigator faculty members were attributed correctly.

These findings indicate that academic medicine’s contribution to biomedical research may be greater than historically reported. Systematically accounting for grants awarded to faculty across medical schools and their affiliated organizations provides a more comprehensive understanding of NIH funding to U.S. medical schools. The AAMC Crosswalk provides a new tool to better estimate the true investment and role of academic medicine in advancing biomedical research.
Implants removal in children: results of a survey among Italian orthopaedic surgeons
Authors: Catena Nunzio , Arrigoni Chiara , Andreacchio Antonio , Toniolo Renato , Verdoni Fabio , Guida Pasquale
Published: June 2024

In the treatment of paediatric limb disorders, the use of metal implants has been increasing over the last decades. Recent studies have addressed the decision of orthopaedic surgeons regarding the removal of implants after the treatment of fracture, and there is a growing consensus within the scientific community supporting the choice of not removing implants in children. This survey aimed to investigate the rationale behind the Italian orthopaedic community’s decision regarding metal implant removal in paediatric patients. An electronic questionnaire was sent to all members of the Italian Paediatric Orthopaedic and Traumatology Society, Italian Orthopaedic and Traumatology Society, Italian Club of Osteosynthesis, and South Italy Society of Orthopaedic and Traumatology. The survey comprised 34 questions about hardware removal after the treatment of long bone fractures, epiphyseal growth plate injuries, slipped capital femoral epiphysis (SCFE), and flat foot. Of the 3500 orthopaedic surgeons who received the questionnaire, 5.5% responded. The leading indications for implant removal were the patient’s intolerance, pain, ROM limitations, and hardware breakage. Removal of elastic nails for long bone fractures, cannulated screws for growth plate injuries, and SCFE and screws for arthroereisis for flat foot correction were analysed in detail. The consensus among Italian Orthopaedic Surgeons is to remove elastic nails and cannulated screws in cases of pain, intolerance, or breakage and to reduce further risks during patient growth. An increasing number of physicians, however, are endorsing and advocating the growing trend in the literature of not routinely removing the hardware.
An Exploratory Analysis of Sociodemographic Factors Associated With Physical Functional Impairment in ICU Survivors
Authors: Watson Megan A. , Sandi Marie , Bixby Johanna , Perry Grace , Offner Patrick J. , Burnham Ellen L. , Jolley Sarah E.
Published: June 2024

IMPORTANCE:

Physical functional impairment is one of three components of postintensive care syndrome (PICS) that affects up to 60% of ICU survivors.

OBJECTIVES:

To explore the prevalence of objective physical functional impairment among a diverse cohort of ICU survivors, both at discharge and longitudinally, and to highlight sociodemographic factors that might be associated with the presence of objective physical functional impairment.

DESIGN, SETTING, AND PARTICIPANTS:

This was a secondary analysis of 37 patients admitted to the ICU in New Orleans, Louisiana, and Denver, Colorado between 2016 and 2019 who survived with longitudinal follow-up data.

MAIN OUTCOMES AND MEASURES:

Our primary outcome of physical functional impairment was defined by handgrip strength and the short physical performance battery. We explored associations between functional impairment and sociodemographic factors that included race/ethnicity, sex, primary language, education status, and medical comorbidities.

RESULTS:

More than 75% of ICU survivors were affected by physical functional impairment at discharge and longitudinally at 3- to 6-month follow-up. We did not see a significant difference in the proportion of patients with physical functional impairment by race/ethnicity, primary language, or education status. Impairment was relatively higher in the follow-up period among women, compared with men, and those with comorbidities. Among 18 patients with scores at both time points, White patients demonstrated greater change in handgrip strength than non-White patients. Four non-White patients demonstrated diminished handgrip strength between discharge and follow-up.

CONCLUSIONS AND RELEVANCE:

In this exploratory analysis, we saw that the prevalence of objective physical functional impairment among ICU survivors was high and persisted after hospital discharge. Our findings suggest a possible relationship between race/ethnicity and physical functional impairment. These exploratory findings may inform future investigations to evaluate the impact of sociodemographic factors on functional recovery.
Recent trends in the incidence of early-onset prostate cancer
Authors: Zheng Yanjun , Mao Jinshui , Yang Lina , Zhu Qiansan
Published: June 2024

Early-onset prostate cancer (EOPC) is relatively uncommon. It is unclear if the incidence of EOPC is evolving. Utilizing data from the SEER database from 2000 to 2020, the study identified prostate cancer cases in men under 55 years, focusing on trends in annual age-adjusted incidence rates (AAIR), stage at presentation, race/ethnicity, and local treatment patterns. The study encompassed 93 071 cases of EOPC, with the median age at diagnosis being 51 years. From 2000 to 2007, the AAIR of EOPC experienced a wave-like increase from 6.9 to 8.3 per 100 000 people. It then sharply declined to 5.4 by 2014, followed by 6 years of stability, and by 2020 it had dropped to its lowest point of 4.5. The trend observed across different racial groups was consistent with the overall pattern, where non-Hispanic Black patients consistently exhibited the highest incidence and the least reduction rate (annual percent change, −1.0; 95% confidence interval, −1.8 to −0.2; P < 0.05). Stage II was the most commonly diagnosed, although its AAIR declined from 4.9 to 1.2 per 100 000 people. From 2010 through 2020, the proportion of receiving prostatectomy decreased from 63.0 to 43.6%. The declining rates of EOPC across diverse racial groups emphasize the critical need for focused research and interventions. Specifically, there is an urgent call to establish a tailored screening protocol for prostate cancer targeting Black youth.
Global, regional, and national burden of ovarian cancer among young women during 1990–2019
Authors: Zhuang Qingyuan , Gu Gaocheng , Chen Jiyu , Tang Zhuojun , Wu Chenxi , Liu Jiahui , Qu Lili
Published: June 2024

Background

Ovarian cancer, the most devastating tumor in women globally, significantly impacts young women, compromising their daily lives and overall well-being. Ovarian cancer represents a significant public health concern due to its extensive physical and psychological consequences.

Material and methods

Data from the Global Burden of Disease were used to assess the global, regional, and national burden of ovarian cancer in young women aged 20–39 from 1990 to 2019. This analysis focused on trends measured by the estimated annual percentage change and explored the socioeconomic impacts via the socio-demographic index (SDI).

Results

During 1990–2019, the incidence and prevalence of ovarian cancer among young women increased globally, with annual rates of 0.74% and 0.89%, respectively. The mortality rate and disability-adjusted life years also rose annually by 0.20% and 0.23%, respectively. A significant burden shift was observed toward regions with lower SDI, with high fasting plasma glucose, BMI, and asbestos exposure identified as prominent risk factors, particularly in lower SDI regions.

Conclusion

Our findings underscore ovarian cancer in young women as an escalating global health challenge, with the burden increasingly shifting toward lower socioeconomic areas. This underscores the necessity for targeted prevention and control strategies for ovarian cancer, focusing on reducing the identified risk factors and ensuring equitable health resource distribution.
A report of research on the digital human and digital medicine in China
Authors: Xie Le , Gu Dongyun , Zhang Ke , Tan Liwen , Tang Lei
Published: June 2024

The progress of science and technology has provided new methods and means for modern medical research, providing strong support and guarantee for modern clinical medicine. Science and technology have not only changed the traditional methods of surgery, but also changed the behavior and service mode of healthcare. The promotion and popularization of digital humans and digital medical research in China have been comprehensively applied in medical education, clinical medicine, aerospace, automotive manufacturing, sports, and artistic performances. This is a new thing, an emerging technology, and a brand-new undertaking.
Progress and prospects in the application of extended reality (XR) in Orthodontics
Authors: Xie Yunyi , Gao Yu , Chen Xuepeng
Published: June 2024

Extended reality (XR) is a collective term for various technologies, including augmented reality (AR), virtual reality (VR), and mixed reality (MR). In recent years, XR has been applied in medical education and training, clinical therapy, and other fields. This scoping review aims to comprehensively summarize the current and potential use of XR in orthodontics. A systematic search was conducted to identify literature on the applications of XR in orthodontic education and training, doctor-patient communication, and orthodontic diagnosis and treatment published from 1999 to 2023. The search was conducted up to August 2023 to identify articles from Embase, PubMed, Web of Science, CNKI, and Google Scholar. A total of 185 studies were screened and 12 articles were reviewed in depth. The applications proposed for XR are educational purposes in 4 studies, and orthodontic diagnosis and treatment in 8 studies. A comparison of studies on different applications indicates that XR technology has varying degrees of positive effects in orthodontic education and treatment. However, XR in orthodontics is still in its early stages of development, and further studies with larger samples and longer clinical trials are needed to confirm the potential positive effects of XR.
Changing Dermatologic Procedural Patterns in the Medicare Population: A National Trend Analysis
Authors: Gronbeck Christian , Jain Neelesh P. , Zhou Albert E. , Sloan Brett , Feng Hao
Published: June 2024

BACKGROUND

Dermatologists are trained in diagnostic and therapeutic procedures for cutaneous lesions, yet comparative trends for basic dermatologic procedures across dermatology providers are lacking at the national level.

OBJECTIVE

To trend common dermatologic procedures among general dermatologists, Mohs surgeons, primary care providers or primary care physicians (PCPs), and nonphysician clinicians (NPCs).

METHODS

Longitudinal analysis of 2016 to 2021 Medicare Public Use Files.

RESULTS

Aggregate dermatologic procedural volume decreased 3.0%. Procedural volume declined among general dermatologists (−11.7%), Mohs surgeons (−16.7%), and PCPs (−41.7%) but increased among NPCs (+57.5%). The proportion of procedures by general dermatologists decreased substantially for premalignant destructions (−6.2%), skin biopsies and shave removals (−4.7%), and malignant excisions (−4.1%) and more notably in counties that were nonmetro (−7.1%), low in income (−6.1%), and with <4.0 dermatologists per 100,000 population (−7.0%).

CONCLUSION

Aggregate procedural volume decreased across the study period with general dermatologists, Mohs surgeons, and PCPs performing a progressively smaller proportion. The increase in procedures by NPCs may help to address demand but underscores the value of formalized procedural training. The procedural decline by general dermatologists in rural and low-income counties and those with baseline dermatologist shortages may exacerbate existing unmet need. Primary limitation included lack of commercial data.