bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing a multimodal corpus of L2 academic English from an English medium of instruction university in China
Authors: Chen Yu-Hua , Harrison Simon , Stevens Michael Paul , Zhou Qianqian
Published: April 2024

This paper describes the rationale for and design of a new multimodal corpus of L2 academic English from a Sino-British university in China: the Corpus of Chinese Academic Written and Spoken English (cawse). The unique context for this corpus provides language samples from Chinese students who use English as a second language (L2) in a preliminary-year programme, which prepares students for academic studies at university level, at a campus where English is used as the Medium of Instruction (emi). Data were collected from a variety of settings, including written (i.e., exam scripts and essays) and spoken assessments (i.e., interviews and presentations), covering the full range of grades awarded to those language samples, as well as from student group interactions during teaching and learning activities. The multimodal nature of the corpus is realised through the availability of selected audio/video recordings accompanied by the orthographically transcribed text. This open-access corpus is designed to help shed light on Chinese students' academic L2 English language use in a variety of written, spoken and multimodal discourses.
Protocolo de investigación del proyecto “Validación transcultural de la Escala de Estereotipos Negativos hacia la Vejez (CENVE) en España, Perú, Salvador y Honduras”
Authors: Palao Loayza Luis , Mendoza Sierra María Isabel
Published: April 2024

Esta investigación se desarrollará entorno a los estereotipos negativos hacia la vejez y las actitudes edadistas en diferentes países de habla hispana. Para ello se utilizará el Cuestionario de Estereotipos Negativos hacia la Vejez (CENVE), ya que, no hay estudios que reporten una validez transcultural en países de Iberoamérica. Por lo tanto, la presente investigación tiene como objetivo evaluar la invarianza de medición transcultural del CENVE en estudiantes universitarios de cuatro países iberoamericanos (España, Perú, Honduras y Salvador). Se estima una participación de 1600 estudiantes universitarios. Se utilizará un análisis factorial confirmatorio multigrupo. La invarianza de medición prueba la hipótesis de que el modelo teórico subyace detrás de un conjunto de puntuaciones es comparable entre grupos. Además, se brindará sugerencias sobre el modelo del CENVE para una mejor evaluación en los cuatro países y puntuaciones confiables, así como las implicaciones de los hallazgos respecto a sus propiedades psicométricas.
Catálogo actualizado de los ejemplares tipo de hongos depositados en el Herbario Nacional de Costa Rica (CR)
Authors: Ruiz Boyer Armando Antonio
Published: April 2024

Antecedentes: El primer catálogo relacionado con los ejemplares tipo de hongos depositados en el Herbario CR fue publicado en el 2002 por Ruiz-Boyer y González-Ball como parte del trabajo titulado “Colección Tipo del Herbario Nacional de Costa Rica (CR). II. Fungi, Lichenes, Bryophyta y Pteridophyta”, donde fueron registrados 17 ejemplares.
Objetivo: Recopilar, actualizar y poner a disposición de la comunidad científica la información asociada a los ejemplares tipo de hongos, que hasta el momento alberga el Herbario CR.
Métodos: La información para este trabajo se obtuvo de las etiquetas asociadas a los ejemplares tipo depositados en el Herbario CR, que se complementó con los protólogos, cuando fue posible consultar las descripciones originales de las especies, así como con la base de datos en línea “Index Fungorum” y la base de datos del Herbario Nacional de Costa Rica.
Resultados y conclusiones: Un total de 99 ejemplares tipo de hongos, que constituyen la referencia nomenclatural de 89 taxones, están depositados hasta ahora en el Herbario CR. Los ejemplares revisados se agruparon en 4 categorías: holotipos (65 ejemplares), isotipos (23), paratipos (10) y tipos (1). Estos ejemplares contribuyen al conocimiento sobre especies nuevas de hongos para la ciencia de Costa Rica.
Dynamic amplifications in railway transition zones: performance evaluation of sleeper configurations using energy criterion
Authors: Jain Avni , Metrikine Andrei V. , Steenbergen Michaël J. M. M. , van Dalen Karel N.
Published: April 2024

Railway transition zones present a major challenge in railway track design mainly due to abrupt jumps in stiffness and differential settlements that result from crossing stiffer structures such as bridges or culverts. Despite numerous efforts to mitigate these transition effects at both the superstructure and substructure levels, a comprehensive solution remains elusive. Substructure-level interventions have demonstrated some effectiveness but are often cost-prohibitive and challenging to implement in existing operational railway transition zones. In contrast, mitigation measures at the superstructure (rail, sleepers, rail-pads, under-sleeper pads) level can be easily installed but have shown limited improvement in site measurements. This study evaluates the influence of different sleeper configurations in transition zones and reduced sleeper spacings on the operation-driven dynamic amplifications in railway transition zones, employing a recently proposed criterion based on the total strain energy in the track-bed layers (ballast, embankment, and subgrade). In addition to this, the influence of the loss of contact between sleepers and ballast (i.e., hanging sleepers), which typically results from the differential settlement, is studied. The first part of the paper provides useful insights regarding the interventions (and/or initial design) in the sleeper configuration and spacing, whereas the second part of the work highlights the need for interventions to deal with the loss of contact between sleeper and ballast. A 2-dimensional finite element model of an embankment-bridge transition was used for the analysis. The results show that it is not possible to mitigate the transition effects completely using the interventions involving sleeper spacing and configuration.
Revealing molecular and cellular heterogeneity in hypopharyngeal carcinogenesis through single-cell RNA and TCR/BCR sequencing
Authors: Tie Cheng-Wei , Zhu Ji-Qing , Yu Zhan , Dou Li-Zhou , Wang Mei-Ling , Wang Gui-Qi , Ni Xiao-Guang
Published: April 2024

Introduction

Hypopharyngeal squamous cell carcinoma (HSCC) is one of the malignant tumors with the worst prognosis in head and neck cancers. The transformation from normal tissue through low-grade and high-grade intraepithelial neoplasia to cancerous tissue in HSCC is typically viewed as a progressive pathological sequence typical of tumorigenesis. Nonetheless, the alterations in diverse cell clusters within the tissue microenvironment (TME) throughout tumorigenesis and their impact on the development of HSCC are yet to be fully understood.

Methods

We employed single-cell RNA sequencing and TCR/BCR sequencing to sequence 60,854 cells from nine tissue samples representing different stages during the progression of HSCC. This allowed us to construct dynamic transcriptomic maps of cells in diverse TME across various disease stages, and experimentally validated the key molecules within it.

Results

We delineated the heterogeneity among tumor cells, immune cells (including T cells, B cells, and myeloid cells), and stromal cells (such as fibroblasts and endothelial cells) during the tumorigenesis of HSCC. We uncovered the alterations in function and state of distinct cell clusters at different stages of tumor development and identified specific clusters closely associated with the tumorigenesis of HSCC. Consequently, we discovered molecules like MAGEA3 and MMP3, pivotal for the diagnosis and treatment of HSCC.

Discussion

Our research sheds light on the dynamic alterations within the TME during the tumorigenesis of HSCC, which will help to understand its mechanism of canceration, identify early diagnostic markers, and discover new therapeutic targets.
The two-directional prospective association between inflammatory bowel disease and neurodegenerative disorders: a systematic review and meta-analysis based on longitudinal studies
Authors: Zong Jiahao , Yang Yue , Wang Hui , Zhang Huipeng , Yang Xiaorong , Yang Xiaoyun
Published: April 2024

Objective

Previous studies reported possible connections between inflammatory bowel disease (IBD) and several neurodegenerative disorders. However, the comprehensive relationships between IBD and various neurodegenerative disorders were not summarized. We executed a meta-analysis of longitudinal studies to provide an estimate of the strength of the two-directional prospective association between IBD and neurodegenerative disorders.

Methods

We accomplished a thorough bibliographic search of PubMed, Web of Science, Embase, PsycINFO, and Cochrane Library databases until June 2023 to locate relevant longitudinal studies. The extracted data were then analyzed via meta-analysis using either a fixed or random effects model.

Results

The final analysis encompassed 27 studies. Individuals with IBD faced an increased risk of developing four neurodegenerative disorders than the general public, namely, Alzheimer’s disease (hazard ratio[HR] = 1.35, 95% confidence interval [CI]: 1.03–1.77, P=0.031), dementia (HR =1.24, 95% CI: 1.13–1.36, P<0.001), multiple sclerosis (HR =2.07, 95% CI:1.42–3.02, P<0.001) and Parkinson’s disease (HR =1.23, 95% CI:1.10–1.38, P<0.001). Two articles reported an increased incidence of amyotrophic lateral sclerosis or multiple system atrophy in IBD patients. Three studies investigated the prospective association between multiple sclerosis and IBD, revealing an elevated risk of the latter in patients with the former. (HR=1.87, 95% CI:1.66–2.10, P<0.001).

Interpretation

These findings verified the two-directional relationship between the brain-gut axis, specifically demonstrating a heightened risk of various neurodegenerative diseases among IBD patients. It may be profitable to prepare screening strategies for IBD patients to find neurodegenerative diseases during the long-term course of treatment for IBD with a view to potential earlier diagnosis and treatment of neurodegenerative diseases, reducing public health and social burden.

Systematic Review Registration

PROSPERO (CRD42023437553).
The Immunomodulatory effect of exosomes in diabetes: a novel and attractive therapeutic tool in diabetes therapy
Authors: Li Na , Hu Lingli , Li Jingyang , Ye Yang , Bao Zhengyang , Xu Zhice , Chen Daozhen , Tang Jiaqi , Gu Ying
Published: April 2024

Exosomes carry proteins, metabolites, nucleic acids and lipids from their parent cell of origin. They are derived from cells through exocytosis, are ingested by target cells, and can transfer biological signals between local or distant cells. Therefore, exosomes are often modified in reaction to pathological processes, including infection, cancer, cardiovascular diseases and in response to metabolic perturbations such as obesity and diabetes, all of which involve a significant inflammatory aspect. Here, we discuss how immune cell-derived exosomes origin from neutrophils, T lymphocytes, macrophages impact on the immune reprogramming of diabetes and the associated complications. Besides, exosomes derived from stem cells and their immunomodulatory properties and anti-inflammation effect in diabetes are also reviewed. Moreover, As an important addition to previous reviews, we describes promising directions involving engineered exosomes as well as current challenges of clinical applications in diabetic therapy. Further research on exosomes will explore their potential in translational medicine and provide new avenues for the development of effective clinical diagnostics and therapeutic strategies for immunoregulation of diabetes.
Collaboration between a cis-interacting natural killer cell receptor and membrane sphingolipid is critical for the phagocyte function
Authors: Karyu Hitomi , Niki Takahiro , Sorimachi Yuriko , Hata Shoji , Shimabukuro-Demoto Shiho , Hirabayashi Tetsuya , Mukai Kojiro , Kasahara Kohji , Takubo Keiyo , Goda Nobuhito , Honke Koichi , Taguchi Tomohiko , Sorimachi Hiroyuki , Toyama-Sorimachi Noriko
Published: April 2024

Inhibitory natural killer (NK) cell receptors recognize MHC class I (MHC-I) in trans on target cells and suppress cytotoxicity. Some NK cell receptors recognize MHC-I in cis, but the role of this interaction is uncertain. Ly49Q, an atypical Ly49 receptor expressed in non-NK cells, binds MHC-I in cis and mediates chemotaxis of neutrophils and type I interferon production by plasmacytoid dendritic cells. We identified a lipid-binding motif in the juxtamembrane region of Ly49Q and found that Ly49Q organized functional membrane domains comprising sphingolipids via sulfatide binding. Ly49Q recruited actin-remodeling molecules to an immunoreceptor tyrosine-based inhibitory motif, which enabled the sphingolipid-enriched membrane domain to mediate complicated actin remodeling at the lamellipodia and phagosome membranes during phagocytosis. Thus, Ly49Q facilitates integrative regulation of proteins and lipid species to construct a cell type-specific membrane platform. Other Ly49 members possess lipid binding motifs; therefore, membrane platform organization may be a primary role of some NK cell receptors.
Autonomous thermal tracking reveals spatiotemporal patterns of seabird activity relevant to interactions with floating offshore wind facilities
Authors: Schneider Stephanie R. , Kramer Sharon H. , Bernstein Sophie B. , Terrill Scott B. , Ainley David G. , Matzner Shari
Published: April 2024

Planning is underway for placement of infrastructure needed to begin offshore wind (OSW) energy generation along the West Coast of the United States and elsewhere in the Pacific Ocean. In contrast to the primarily nearshore windfarms currently in the North Atlantic, the seabird communities inhabiting Pacific Wind Energy Areas (WEAs) include significant populations of species that fly by dynamic soaring, a behavior dependent on wind and in which flight height increases steeply with wind speed. Therefore, a more precise and detailed assessment of their 3D airspace use is needed to better understand the potential collision risks that OSW turbines may present to these seabirds. Toward this end, a novel technology called the ThermalTracker-3D (TT3D), which uses thermal imaging and stereo vision, was developed to render high-resolution (on average within ±5 m) flight tracks and related behavior of seabirds. The technology was developed and deployed on a wind-profiling LiDAR buoy in the Humboldt WEA, located 34 to 57 km off California’s coast. During the at-sea deployment between 24 May and 13 August 2021, the TT3D successfully tracked birds moving between 10 and 500 m from the device, around the clock, and in all weather conditions; a total of 1407 detections and their corresponding 3D flight trajectories were recorded. Mean altitudes of detections ranged 6-295 m above sea level (asl). Considering the degree of overlap with anticipated rotor swept zones (RSZ), which extend 25-260 m asl, 79% of detected birds (per m3 of airspace) moved below the RSZ, 21% moved at heights overlapping the RSZ, and another 0.04% occurred at heights exceeding the RSZ. The high-resolution tracks provided valuable insight into seabird space use, especially at heights that make them vulnerable to collision during various environmental conditions (e.g., darkness, strong winds). Observations made by the TT3D will be useful in filling critical knowledge gaps related to estimating collision and avoidance between seabirds and OSW facilities in the Pacific and elsewhere. Future research will focus on enhancing the TT3D’s identification capabilities to the lowest taxon through validation studies and artificial intelligence, further contributing to seabird conservation efforts associated with OSW.
Modelling esophageal adenocarcinoma and Barrett’s esophagus with patient-derived organoids
Authors: Milne Julia V. , Mustafa Ebtihal H. , Clemons Nicholas J.
Published: April 2024

Currently, esophageal adenocarcinoma (EAC) research is hindered by a dearth of adequate models to study this disease. Traditional cell line and genetically engineered mouse models are lacking in biological and physiological significance, whilst the inefficiency of patient-derived xenografts limit their potential applications. This review describes the landscape of EAC research using patient-derived organoids (PDOs). Here, we detail the methods of establishment and optimization of EAC PDO cultures, as well as current and prospective applications of these models. We further highlight a crucial knowledge gap in the mechanisms of EAC transformation from its precursor lesion, Barrett’s esophagus (BE). As such, we also describe the culture requirements of BE PDOs and attempts to model tumorigenesis using PDO models.
Reinforcement feedback impairs locomotor adaptation and retention
Authors: Hill Christopher M. , Sebastião Emerson , Barzi Leo , Wilson Matt , Wood Tyler
Published: April 2024

Introduction

Locomotor adaptation is a motor learning process used to alter spatiotemporal elements of walking that are driven by prediction errors, a discrepancy between the expected and actual outcomes of our actions. Sensory and reward prediction errors are two different types of prediction errors that can facilitate locomotor adaptation. Reward and punishment feedback generate reward prediction errors but have demonstrated mixed effects on upper extremity motor learning, with punishment enhancing adaptation, and reward supporting motor memory. However, an in-depth behavioral analysis of these distinct forms of feedback is sparse in locomotor tasks.

Methods

For this study, three groups of healthy young adults were divided into distinct feedback groups [Supervised, Reward, Punishment] and performed a novel locomotor adaptation task where each participant adapted their knee flexion to 30 degrees greater than baseline, guided by visual supervised or reinforcement feedback (Adaptation). Participants were then asked to recall the new walking pattern without feedback (Retention) and after a washout period with feedback restored (Savings).

Results

We found that all groups learned the adaptation task with external feedback. However, contrary to our initial hypothesis, enhancing sensory feedback with a visual representation of the knee angle (Supervised) accelerated the rate of learning and short-term retention in comparison to monetary reinforcement feedback. Reward and Punishment displayed similar rates of adaptation, short-term retention, and savings, suggesting both types of reinforcement feedback work similarly in locomotor adaptation. Moreover, all feedback enhanced the aftereffect of locomotor task indicating changes to implicit learning.

Discussion

These results demonstrate the multi-faceted nature of reinforcement feedback on locomotor adaptation and demonstrate the possible different neural substrates that underly reward and sensory prediction errors during different motor tasks.
Classification and transfer learning of sleep spindles based on convolutional neural networks
Authors: Liang Jun , Belkacem Abdelkader Nasreddine , Song Yanxin , Wang Jiaxin , Ai Zhiguo , Wang Xuanqi , Guo Jun , Fan Lingfeng , Wang Changming , Ji Bowen , Wang Zengguang
Published: April 2024

Background

Sleep plays a critical role in human physiological and psychological health, and electroencephalography (EEG), an effective sleep-monitoring method, is of great importance in revealing sleep characteristics and aiding the diagnosis of sleep disorders. Sleep spindles, which are a typical phenomenon in EEG, hold importance in sleep science.

Methods

This paper proposes a novel convolutional neural network (CNN) model to classify sleep spindles. Transfer learning is employed to apply the model trained on the sleep spindles of healthy subjects to those of subjects with insomnia for classification. To analyze the effect of transfer learning, we discuss the classification results of both partially and fully transferred convolutional layers.

Results

The classification accuracy for the healthy and insomnia subjects’ spindles were 93.68% and 92.77%, respectively. During transfer learning, when transferring all convolutional layers, the classification accuracy for the insomnia subjects’ spindles was 91.41% and transferring only the first four convolutional layers achieved a classification result of 92.80%. The experimental results demonstrate that the proposed CNN model can effectively classify sleep spindles. Furthermore, the features learned from the data of the normal subjects can be effectively applied to the data for subjects with insomnia, yielding desirable outcomes.

Discussion

These outcomes underscore the efficacy of both the collected dataset and the proposed CNN model. The proposed model exhibits potential as a rapid and effective means to diagnose and treat sleep disorders, thereby improving the speed and quality of patient care.
Association between blood chromium and hepatic steatosis assessed by liver ultrasound transient elastography: National Health and Nutrition Examination Survey 2017–2020
Authors: Xiang Yingying , Zhou Ruonan , Wang Ziwei , Xue Yingying , Cao Yue , Shen Lixuan , Zhu Ziwei , Xu Pingyuan , Zhou Guowei , Shang Wenbin
Published: April 2024

Background

Hepatic steatosis is a significant pathological feature of fatty liver disease (FLD) which is widely spread with no effective treatment available. Previous studies suggest that chromium (Cr) intake reduces lipid deposition in the liver in animals. However, the connection between blood Cr and hepatic steatosis among humans remains inconclusive.

Methods

Using the data from the National Health and Nutrition Examination Survey (NHANES) 2017–2020, we performed a cross-sectional analysis, including 4,926 participants. The controlled attenuation parameter (CAP) measured by the vibration controlled transient elastography (VCTE) was used to evaluate the degree of liver steatosis. Weighted univariate regression, multivariate linear regression, smooth fitting curves and subgroup analysis were used. In addition, we carried out trend tests, multiple interpolations, and interaction analyses to conduct sensitivity analyses.

Results

After adjusting with various covariables, multivariate linear regression analysis demonstrated a significant negative correlation between blood Cr and CAP [β (95% CI) = −5.62 (−11.02, −0.21)]. The negative correlation between blood Cr and CAP was more significant in the males, 50–59 years, overweight, hypercholesterolemia, HDL-C ≥ 65 mg/dL, HbA1c (5.70–6.10 %), HOMA-IR (0.12–2.76), total bilirubin (0.30–0.40 mg/dL), ever alcohol consumption subjects. Of note, the relationships between blood Cr and CAP followed a U-shaped curve in the smokers and non-smokers, with blood Cr thresholds of 0.48, 0.69 μg/L, respectively.

Conclusions

There is an independently negative correlation between blood Cr and hepatic steatosis in American. Our study provides clinical researchers with a new insight into the prospective prevention of hepatic steatosis.
Metabolome-wide Mendelian randomization reveals causal effects of betaine and N-acetylornithine on impairment of renal function
Authors: Liu Yuqing , Ling Lilu , Shen Yue , Bi Xiao
Published: April 2024

Background

Chronic kidney disease (CKD) is a common public health problem, which is characterized as impairment of renal function. The associations between blood metabolites and renal function remained unclear. This study aimed to assess the causal effect of various circulation metabolites on renal function based on metabolomics.

Methods

We performed a two-sample Mendelian randomization (MR) analysis to estimate the causality of genetically determined metabolites on renal function. A genome-wide association study (GWAS) of 486 metabolites was used as the exposure, while summary-level data for creatinine-based estimated glomerular filtration rate (eGFR) or CKD occurrence were set the outcomes. Inverse variance weighted (IVW) was used for primary causality analysis and other methods including weight median, MR-egger, and MR-PRESSO were applied as complementary analysis. Cochran Q test, MR-Egger intercept test, MR-PRESSO global test and leave-one-out analysis were used for sensitivity analysis. For the identified metabolites, reverse MR analysis, linkage disequilibrium score (LDSC) regression and multivariable MR (MVMR) analysis were performed for further evaluation. The causality of the identified metabolites on renal function was further validated using GWAS data for cystatin-C-based eGFR. All statistical analyses were performed in R software.

Results

In this MR analysis, a total of 44 suggestive associations corresponding to 34 known metabolites were observed. After complementary analysis and sensitivity analysis, robust causative associations between two metabolites (betaine and N-acetylornithine) and renal function were identified. Reverse MR analysis showed no causal effects of renal function on betaine and N-acetylornithine. MVMR analysis revealed that genetically predicted betaine and N-acetylornithine could directly influence independently of each other. The causal effects of betaine and N-acetylornithine were also found on cystatin-C-based eGFR.

Conclusion

Our study provided evidence to support the causal effects of betaine and N-acetylornithine on renal function. These findings required further investigations to conduct mechanism exploration and drug target selection of these identified metabolites.
Six new polyphenolic metabolites isolated from the Suillus granulatus and their cytotoxicity against HepG2 cells
Authors: Zhao Hanyu , Xiong Miaomiao , Yang Xiaomin , Yao Lan , Wang Zeyan , Wang Li-an , Li Zhuang , Zhang Jinxiu , Lv Jianhua
Published: April 2024

Edible mushrooms are an important source of nutraceuticals and for the discovery of bioactive metabolites as pharmaceuticals. In this work, six new polyphenolic metabolites suillusol A-D (1–4), suillusinoic acid (5), ethyl suillusinoate (6), were isolated from the Suillus granulatus. The structures of new compounds were elucidated using high-resolution electrospray ionization mass spectroscopy, nuclear magnetic resonance data, and single-crystal X-ray diffraction analysis. As far as we know, compound 1 represents an unprecedented type of natural product and compound 3 represents a new type of polyphenol fungal pigment, which may be biosynthetically related to thelephoric acid. The cytotoxicity against HepG2 cells of the new compounds were also evaluated. Compound 2 demonstrate significant inhibitory activity against HepG2 cells with IC50 values of 10.85 μM, surpassing that of positive control cisplatin. Moreover, compound 1 and 3 also exhibited moderate cytotoxic activity with their IC50 values measured at 35.60 and 32.62 μM, respectively. Our results indicate that S. granulatus is a rich source of chemical constituents that may provide new lead compounds for the development of anticancer agents.
The expression and role of the Lem-D proteins Ankle2, Emerin, Lemd2, and TMPO in triple-negative breast cancer cell growth
Authors: Rose Maddison , Burgess Joshua T. , Cheong Chee Man , Adams Mark N. , Shahrouzi Parastoo , O’Byrne Kenneth J. , Richard Derek J. , Bolderson Emma
Published: April 2024

Background

Triple-negative breast cancer (TNBC) is a sub-classification of breast carcinomas, which leads to poor survival outcomes for patients. TNBCs do not possess the hormone receptors that are frequently targeted as a therapeutic in other cancer subtypes and, therefore, chemotherapy remains the standard treatment for TNBC. Nuclear envelope proteins are frequently dysregulated in cancer cells, supporting their potential as novel cancer therapy targets. The Lem-domain (Lem-D) (LAP2, Emerin, MAN1 domain, and Lem-D) proteins are a family of inner nuclear membrane proteins, which share a ~45-residue Lem-D. The Lem-D proteins, including Ankle2, Lemd2, TMPO, and Emerin, have been shown to be associated with many of the hallmarks of cancer. This study aimed to define the association between the Lem-D proteins and TNBC and determine whether these proteins could be promising therapeutic targets.

Methods

GENT2, TCGA, and KM plotter were utilized to investigate the expression and prognostic implications of several Lem-D proteins: Ankle2, TMPO, Emerin, and Lemd2 in publicly available breast cancer patient data. Immunoblotting and immunofluorescent analysis of immortalized non-cancerous breast cells and a panel of TNBC cells were utilized to establish whether protein expression of the Lem-D proteins was significantly altered in TNBC. SiRNA was used to decrease individual Lem-D protein expression, and functional assays, including proliferation assays and apoptosis assays, were conducted.

Results

The Lem-D proteins were generally overexpressed in TNBC patient samples at the mRNA level and showed variable expression at the protein level in TNBC cell lysates. Similarly, protein levels were generally negatively correlated with patient survival outcomes. siRNA-mediated depletion of the individual Lem-D proteins in TNBC cells induced aberrant nuclear morphology, decreased proliferation, and induced cell death. However, minimal effects on nuclear morphology or cell viability were observed following Lem-D depletion in non-cancerous MCF10A cells.

Conclusion

There is evidence to suggest that Ankle2, TMPO, Emerin, and Lemd2 expressions are correlated with breast cancer patient outcomes, but larger patient sample numbers are required to confirm this. siRNA-mediated depletion of these proteins was shown to specifically impair TNBC cell growth, suggesting that the Lem-D proteins may be a specific anti-cancer target.
Initial investigation on ultrasound-guided percutaneous biopsy of lesions in the first hepatic hilum with fusion of ultrasound and multimodal imaging cognitive guidance
Authors: Zeng Xian-Tao , Liang Xia , Hong Zhi-Liang , Chen Sheng , Yang Jian-Chuan , Lin Yu-cheng , Wu Song-Song
Published: April 2024

Purpose

This study aims to evaluate the efficacy and safety of ultrasound-guided percutaneous biopsy of the first hepatic hilum lesion, and examine its clinical value of diagnosis and treatment.

Methods

We conducted a retrospective study on patients diagnosed with the first hepatic hilum lesions at Fujian Provincial Hospital between February 2015 and October 2022. We selected patients who had lesions in the first hepatic hilum(including a 2cm surrounding area of the left/right hepatic ducts and upper-middle segment of the common bile duct) and the liver periphery(in the peripheral area of the liver, outside of the above-mentioned first hepatic porta region). These patients underwent percutaneous ultrasound-guided core needle biopsy (PUS-CNB) with cognitive fusion guidance using CT, MRI, or PET-CT. We compared the safety and efficacy of PUS-CNB in the first hepatic hilum and the liver periphery to explore the value of PUS-CNB in optimizing the clinical treatment of the first hepatic hilum lesions.

Results

The studied includes 38 cases of the first hepatic hilum cases (18 females; 20 males), 23 presented with mass-forming tumors while the remaining 15 exhibited diffuse infiltrative tumors, with an average diameter of 4.65± 2.51 cm. The percutaneous biopsy procedure, conducted under ultrasound guidance, had an average operation time of 14.55 ± 2.73 minutes, and resulted in a postoperative bleeding volume of approximately 10.79 ± 2.79 ml. The diagnostic success rate was noted to be as high as 92.11% among the participants who underwent percutaneous biopsy of the first hepatic hilum. Procedural complications, such as bleeding, bile leakage, intestinal perforation, infection or needle tract seeding, did not occur during or after the biopsy procedure. Affected by biopsy results, 5 altered their clinical treatment plans accordingly, 24patients received non-surgical treatment, 9 underwent surgical treatment, 5 underwent radiofrequency ablation for the lesions. The study comprised a total of 112 cases for percutaneous biopsy of the liver periphery. The safety and effectiveness of the two biopsy techniques were comparable, with diagnostic success rates of 92.11% VS. 94.34%, respectively (p = 0.61).

Conclusion

Cognitive fusion of ultrasound and multi-modal imaging for the first hepatic hilum lesion puncture biopsy is a safe and effective diagnostic procedure, with better diagnostic rate, may improve clinical value of diagnosis and treatment of various diseases.
Targeting ACAT1 in cancer: from threat to treatment
Authors: Sun Tie , Xiao Xuan
Published: April 2024

Altered cholesterol metabolism has been identified as a critical feature of cancers. Cholesterol functions as the main component of cell membrane, cholesterol and is required for sustaining membrane integrity and mediating signaling transduction for cell survival. The intracellular level of cholesterol is dynamically regulated. Excessive cholesterol could be converted to less toxic cholesteryl esters by acyl-coenzyme A:cholesterol acyltransferases (ACATs). While ACAT2 has limited value in cancers, ACAT1 has been found to be widely participated in tumor initiation and progression. Moreover, due to the important role of cholesterol metabolism in immune function, ACAT1 is also essential for regulating anti-tumor immunity. ACAT1 inhibition may be exploited as a potential strategy to enhance the anti-tumor immunity and eliminate tumors. Herein, a comprehensive understanding of the role of ACAT1 in tumor development and anti-tumor immunity may provide new insights for anti-tumor strategies.
Prevalence and plasma exosome-derive microRNA diagnostic biomarker screening of adolescent idiopathic scoliosis in Yunnan Province, China
Authors: Yuan Ping , Wang Zhi-Hua , Jiang Hong , Wang Yang-Hao , Yang Jian-Yi , Li Lu-Ming , Wang Wen-Tong , Chen Jing , Li Deng-Hui , Long Sheng-Yu , Zhang Wan , He Fei , Wang Wei-Zhou
Published: April 2024

Background

Idiopathic scoliosis significantly affects the physical and mental health of children and adolescents, with varying prevalence rates in different regions. The occurrence of idiopathic scoliosis is associated with genetic regulation and biochemical factors, but the changes in exosome-derived miRNA profiles among idiopathic scoliosis patients remain unclear. This study aimed to determine the prevalence of idiopathic scoliosis in Yunnan Province, China, and identify key exosome-derived miRNAs in idiopathic scoliosis through a cohort study.

Methods

From January 2018 to December 2020, a cross-sectional study on idiopathic scoliosis in children and adolescents was conducted in Yunnan Province. A total of 84,460 students from 13 cities and counties in Yunnan Province participated in a scoliosis screening program, with ages ranging from 7 to 19 years. After confirmation through screening and imaging results, patients with severe idiopathic scoliosis and normal control individuals were selected using propensity matching. Subsequently, plasma exosome-derived miRNA sequencing and RT-qPCR validation were performed separately. Based on the validation results, diagnostic performance analysis and target gene prediction were conducted for differential plasma exosome-derived miRNAs.

Results

The overall prevalence of idiopathic scoliosis in children and adolescents in Yunnan Province was 1.10%, with a prevalence of 0.87% in males and 1.32% in females. The peak prevalence was observed at age 13. Among patients diagnosed with idiopathic scoliosis, approximately 12.8% had severe cases, and there were more cases of double curvature than of single curvature, with thoracolumbar curvature being the most common in the single-curvature group. Sequencing of plasma exosome-derived miRNAs associated with idiopathic scoliosis revealed 56 upregulated and 153 downregulated miRNAs. Further validation analysis confirmed that hsa-miR-27a-5p, hsa-miR-539-5p, and hsa-miR-1246 have potential diagnostic value.

Conclusions

We gained insights into the epidemiological characteristics of idiopathic scoliosis in Yunnan Province and conducted further analysis of plasma exosome-derived miRNA changes in patients with severe idiopathic scoliosis. This study has provided new insights for the prevention and diagnosis of idiopathic scoliosis, paving the way for exploring clinical biomarkers and molecular regulatory mechanisms. However, further validation and elucidation of the detailed biological mechanisms underlying these findings will be required in the future.
Scandinavian perspectives on life support at the border of viability
Authors: Syltern Janicke
Published: April 2024

Advances in neonatal medicine have allowed us to rescue extremely preterm infants. However, both long-term vulnerability and the burden of treatment in the neonatal period increase with decreasing gestational age. This raises questions about the justification of life support when a baby is born at the border of viability, and has led to a so-called “grey zone”, where many professionals are unsure whether provision of life support is in the child's best interest. Despite cultural, political and economic similarities, the Scandinavian countries differ in their approach to periviable infants, as seen in their respective national guidelines and practices. In Sweden, guidelines and practice are more rescue-focused at the lower end of the border of viability, Danish guidelines emphasizes the need to involve parental views in the decision-making process, whereas Norway appears to be somewhere in between. In this paper, I will give an overview of national consensus documents and practices in Norway, Sweden and Denmark, and reflect on the ethical justification for the different approaches.
Diethyldithiocarbamate-ferrous oxide nanoparticles inhibit human and mouse glioblastoma stemness: aldehyde dehydrogenase 1A1 suppression and ferroptosis induction
Authors: Abu-Serie Marwa M. , Osuka Satoru , Heikal Lamiaa A. , Teleb Mohamed , Barakat Assem , Dudeja Vikas
Published: April 2024

The development of effective therapy for eradicating glioblastoma stem cells remains a major challenge due to their aggressive growth, chemoresistance and radioresistance which are mainly conferred by aldehyde dehydrogenase (ALDH)1A1. The latter is the main stemness mediator via enhancing signaling pathways of Wnt/β-catenin, phosphatidylinositol 3-kinase/AKT, and hypoxia. Furthermore, ALDH1A1 mediates therapeutic resistance by inactivating drugs, stimulating the expression of drug efflux transporters, and detoxifying reactive radical species, thereby apoptosis arresting. Recent reports disclosed the potent and broad-spectrum anticancer activities of the unique nanocomplexes of diethyldithiocarbamate (DE, ALDH1A1 inhibitor) with ferrous oxide nanoparticles (FeO NPs) mainly conferred by inducing lipid peroxidation-dependent non-apoptotic pathways (iron accumulation-triggered ferroptosis), was reported. Accordingly, the anti-stemness activity of nanocomplexes (DE-FeO NPs) was investigated against human and mouse glioma stem cells (GSCs) and radioresistant GSCs (GSCs-RR). DE-FeO NPs exhibited the strongest growth inhibition effect on the treated human GSCs (MGG18 and JX39P), mouse GSCs (GS and PDGF-GSC) and their radioresistant cells (IC50 ≤ 70 and 161 μg/mL, respectively). DE-FeO NPs also revealed a higher inhibitory impact than standard chemotherapy (temozolomide, TMZ) on self-renewal, cancer repopulation, chemoresistance, and radioresistance potentials. Besides, DE-FeO NPs surpassed TMZ regarding the effect on relative expression of all studied stemness genes, as well as relative p-AKT/AKT ratio in the treated MGG18, GS and their radioresistant (MGG18-RR and GS-RR). This potent anti-stemness influence is primarily attributed to ALDH1A1 inhibition and ferroptosis induction, as confirmed by significant elevation of cellular reactive oxygen species and lipid peroxidation with significant depletion of glutathione and glutathione peroxidase 4. DE-FeO NPs recorded the optimal LogP value for crossing the blood brain barrier. This in vitro novel study declared the potency of DE-FeO NPs for collapsing GSCs and GSCs-RR with improving their sensitivity to chemotherapy and radiotherapy, indicating that DE-FeO NPs may be a promising remedy for GBM. Glioma animal models will be needed for in-depth studies on its safe effectiveness.
The pharmacoepigenetic paradigm in cancer treatment
Authors: Ocaña-Paredes Belén , Rivera-Orellana Sebastián , Ramírez-Sánchez David , Montalvo-Guerrero Juliana , Freire María Paula , Espinoza-Ferrao Samantha , Altamirano-Colina Adriana , Echeverría-Espinoza Paulina , Ramos-Medina María José , Echeverría-Garcés Gabriela , Granda-Moncayo Danilo , Jácome-Alvarado Andrea , Andrade María Gabriela , López-Cortés Andrés
Published: April 2024

Epigenetic modifications, characterized by changes in gene expression without altering the DNA sequence, play a crucial role in the development and progression of cancer by significantly influencing gene activity and cellular function. This insight has led to the development of a novel class of therapeutic agents, known as epigenetic drugs. These drugs, including histone deacetylase inhibitors, histone acetyltransferase inhibitors, histone methyltransferase inhibitors, and DNA methyltransferase inhibitors, aim to modulate gene expression to curb cancer growth by uniquely altering the epigenetic landscape of cancer cells. Ongoing research and clinical trials are rigorously evaluating the efficacy of these drugs, particularly their ability to improve therapeutic outcomes when used in combination with other treatments. Such combination therapies may more effectively target cancer and potentially overcome the challenge of drug resistance, a significant hurdle in cancer therapy. Additionally, the importance of nutrition, inflammation control, and circadian rhythm regulation in modulating drug responses has been increasingly recognized, highlighting their role as critical modifiers of the epigenetic landscape and thereby influencing the effectiveness of pharmacological interventions and patient outcomes. Epigenetic drugs represent a paradigm shift in cancer treatment, offering targeted therapies that promise a more precise approach to treating a wide spectrum of tumors, potentially with fewer side effects compared to traditional chemotherapy. This progress marks a step towards more personalized and precise interventions, leveraging the unique epigenetic profiles of individual tumors to optimize treatment strategies.
Structural characterization and immunostimulant activities of polysaccharides fractionated by gradient ethanol precipitation method from Panax ginseng C. A. Meyer
Authors: Xu Mengran , Ren Jing , Jiang Ziye , Zhou Shuo , Wang Enpeng , Li Hui , Wu Wei , Zhang Xiaoyu , Wang Jing , Jiao Lili
Published: April 2024

Panax ginseng C. A. Meyer is a dual-purpose plant for medicine and food, its polysaccharide is considered as an immune enhancer. Four polysaccharides, WGP-20-F, WGP-40-F, WGP-60-F and WGP-80-F were obtained from ginseng via water extraction and gradient ethanol precipitation with different molecular weights (Mw) of 1.720 × 106, 1.434 × 106, 4.225 × 104 and 1.520 × 104 Da, respectively. WGP-20-F and WGP-40-F which with higher Mw and a triple-helix structure are glucans composed of 4-ɑ-Glcp, do not show remarkable immunoregulatory effects. WGP-60-F and WGP-80-F are heteropolysaccharides mainly composed of 4-ɑ-Glcp and also contain t-ɑ-Araf, 5-ɑ-Araf and 3,5-ɑ-Araf. They are spherical branched conformations without a triple-helix structure and can effectively increase the index of immune organs, lymphocyte proliferation, activate macrophages to regulate the immune system in mice and further enhance immune functions by improving delayed-type hypersensitivity reaction and antibody response. These results indicated that WGP-60-F and WGP-80-F could be used as potential immune enhancers, and gradient ethanol precipitation can be applied for the preparation of ginseng bioactive polysaccharide.
Theory and design consideration of a THz superradiant waveguide FEL
Authors: Weinberg Amir , Gover Avraham , Nause Ariel , Friedman Aharon , Ianconescu Reuven , Fisher Andrew , Musumeci Pietro , Fukasawa Atsushi , Rosenzweig James
Published: April 2024

We present theoretical analysis and design considerations of a THz superradiant FEL. We derive analytical expressions for the spectral parameter of THz radiation, emitted superradiantly in a rectangular waveguide using a Longitudinal Section Magnetic mode expansion. The results compare well with numerical simulations using UCLA GPTFEL code. GPT simulations of the accelerator e-beam transport show that the chirp provided by a hybrid photocathode RF gun, can produce tight bunching at the undulator site below σ = 100fs. This enables intense superradiant emission up to 3THz, limited by the beam bunching factor. Phase-space analysis of the beam transport indicates that keeping the beam bunching parameter small enough for higher THz frequency operation is limited by the energy spread of the beam in the gun.
Effect of circadian rhythm and menstrual cycle on physical performance in women: a systematic review
Authors: Beníčková Michaela , Gimunová Marta , Paludo Ana Carolina
Published: April 2024

The literature has extensively investigated potential factors influencing women’s performance, including the menstrual cycle and the circadian rhythm. However, review articles exploring the combined influence of both factors remain lacking in the literature. The study aimed to systematically review the literature on the relationship between the circadian rhythm and menstrual cycle on physical performance in women. The review followed the PRISMA guidelines. The search was performed on the Web of Science, PubMed, Scopus, SPORTDiscus, and Google Scholar databases. Of the 1205 records identified, four articles met the inclusion criteria. From four articles, two studies found a significant interaction between the time of day and phase of the menstrual cycle with physical performance. The isometric strength increased in the afternoon in the mid-luteal phase (versus the morning in the mid-luteal phase, p < 0.05), and the maximum cycling power was higher in the afternoon in the mid-follicular phase (versus the morning in the mid-follicular phase, p < 0.01). Our findings suggest that the time of day and the menstrual cycle phase affect physical performance, with the daytime potentially having a more significant influence. However, the results should be interpreted cautiously due to the limited studies and diverse methodologies used to monitor the menstrual cycle phase. This review reinforces the need for further investigation to understand better the combined effects of the circadian rhythm and menstrual cycle on women’s physical performance.

Systematic Review Registration:

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=380965, identifier CRD42022380965.
Correlates of climate change skepticism
Authors: Leka Jona , Furnham Adrian
Published: April 2024

While much research has examined the correlates of climate change beliefs from an alarmist perspective, less work has systematically measured climate change skepticism. This study aims to create a comprehensive tool capturing climate skeptics’ beliefs and test its association with individual difference variables. 502 European adults completed a 22-item questionnaire on climate change (CC) skepticism as well as measures of ambiguity tolerance, belief in a just world (BJW), dark-side personality traits, and self-esteem. Principal components analysis revealed a four dimension structure of CC. Political ideology was the most consistent and significant predictor across the climate change skepticism factors. Dark-side traits, also played a role. Future research should further validate this measure and explore how climate change information could be tailored to different audiences. Understanding the nuances and causes of climate skepticism can enable more effective communication to promote sustainability.