bluuebunny/crossref_metadata_2025 huggingface dataset:
Extracellular vesicles as mediators of stress response in embryo-maternal communication
Authors: Mousavi Seyed Omid , Reshi Qurat Ul Ain , Godakumara Kasun , Kodithuwakku Suranga , Fazeli Alireza
Published: August 2024

Introduction: The pivotal role of extracellular vesicles (EVs) in facilitating effective communication between the embryo and maternal cells during the preimplantation stage of pregnancy has been extensively explored. Nonetheless, inquiries persist regarding the alterations in EV cargo from endometrial cells under stress conditions and its potential to elicit specific stress responses in trophoblast cells. Thus, the aim of this study was to elucidate the involvement of EV miRNA miRNAs in transmitting stress signals from maternal cells to trophoblasts.

Methods: The receptive endometrial epithelium analogue RL95-2 cells were subjected to stress induction with 200 µM CoCl2 for 24 h before EV isolation. JAr trophoblast spheroids, which serve as embryos, were subjected to treatment with stressed or unstressed EVs derived from RL95-2 cells for 24 h. Transcriptomic alterations in the treated JAr spheroids as well as in the untreated group, as a negative control, were investigated by mRNA sequencing. Furthermore, the changes in EV miRNAs were assessed by sequencing EV samples.

Results: A comprehensive analysis comparing the miRNA profiles between stressed and unstressed EVs revealed significant changes in 25 miRNAs. Furthermore, transcriptomic analysis of JAr spheroids treated with stressed RL95-2EVs versus unstressed EVs or the untreated group demonstrated 6 and 27 differentially expressed genes, respectively. Pathway enrichment analysis showed that stressed EVs induce alterations in gene expression in trophoblast cells, which is partially mediated by EV microRNAs.

Discussion: Our results suggest that EVs can transfer stress signals from endometrial cells to the embryo. These discoveries shed new light on the mechanism underlying implantation failures under stress conditions. Unraveling the role of EVs in transmitting stress signals, can extend our knowledge to pave the way for targeted interventions to manage stress-related implantation failures.
The single-cell atlas of the epididymis in mice reveals the changes in epididymis function before and after sexual maturity
Authors: Zhang Jiaxin , Xie Ye , Wang Xiaoyan , Kang Yafei , Wang Chuxiong , Xie Qinying , Dong Xinyi , Tian Yonghong , Huang Donghui
Published: August 2024

Introduction: The epididymis is important for sperm transport, maturation, and storage.

Methods: The head and tail of the epididymis of 5-week-old and 10-week-old C57 BL/6J male mice were used for single-cell sequencing.

Results: 10 cell types including main, basal, and narrow/clear cells are identified. Next, we performed cell subgroup analysis, functional enrichment analysis, and differentiation potential prediction on principal cells, clear cells, and basal cells. Our study indicates that the principal cells are significantly involved in sperm maturation, as well as in antiviral and anti-tumor immune responses. Clear cells are likely to play a crucial role in safeguarding sperm and maintaining epididymal pH levels. Basal cells are implicated in the regulation of inflammatory and stress responses. The composition and functions of the various cell types within the epididymis undergo significant changes before and after sexual maturity. Furthermore, pseudo-temporal analysis elucidates the protective and supportive roles of epididymal cells in sperm maturation during sexual maturation.

Discussion: This study offers a theoretical framework and forecasts for the investigation of epididymal sperm maturation and epididymal immunity.
Multi-paradigm modelling and control of microgrid systems for better power stability in the Rockaways
Authors: Aljarbouh Ayman , Zubov Dmytro , Moghrabi Issam A. R.
Published: August 2024

The Rockaways Peninsula faces issues related to congestion and power outages during times of peak usage. Additionally, it is susceptible to disruptions caused by disasters such as hurricanes and storms. In this paper, we propose a new methodology that employs multi-paradigm modelling and control for the design and implementation of interconnected microgrid systems in the Rockaways. Microgrids are small-scale power networks that incorporate renewable energy technologies for power generation and distribution to enhance the control of energy supply and demand. Multi-paradigm modelling is employed to describe microgrids’ dynamic behavior more accurately by integrating system dynamics, agent-based modelling, as well as discrete event and continuous time simulation. We use agent-based models to describe the behavior of separate microgrid elements and the microgrid as a whole. Discrete event/continuous time simulation is used to analyze real-time operation of electrical parameters, such as voltage, current and frequency. Thus, the design, analysis and performance of microgrids are improved. Also, control strategies are used for the purpose of enabling the microgrids to operate effectively by responding to changes in power supply and demand and minimizing the effects of disturbances. The findings of this study demonstrate the feasibility and resilience benefits of incorporating multi-paradigm modelling and control in the design and management of microgrid systems in the Rockaways, which can result in the development of more durable, efficient, and sustainable energy systems in the region.
Driving towards sustainability: exploring risk perceptions of fossil fuels, e-fuels, and electric drives in individual transport
Authors: Rößler Eva , Schmeckel Tim , Kesselheim Ute , Arning Katrin
Published: August 2024

The transportation sector is a significant contributor to CO2 emissions, necessitating the adoption of alternative drive technologies to achieve decarbonization. This study investigates public perceptions of fossil fuels, e-fuels, and electric drives, with the aim of identifying factors influencing risk perceptions, perceived efficacy in combating climate change, and readiness to use or purchase cars with these technologies. Therefore, a quantitative study using a questionnaire (N = 141) was conducted. The results indicate that e-fuels and electric drives are perceived more positively than fossil fuels. E-fuels were found to have the lowest risk perceptions. Differences in cognitive and affective risk perceptions, as well as in financial, environmental, and health-related risks, were observed across drive types. Car affinity was found to correlate negatively with risk perceptions of e-fuels and fossil fuels, but positively with electric drives. The risk perception of global warming showed an inverse relationship. Regarding the prediction of readiness, differences were found between e-fuels and electric drives in terms of the influencing factors on readiness. The study contributes to the understanding of public perceptions by providing a comparison between different drive technologies and offers valuable insights for developing targeted communication strategies.
Sliding mode control based on maximum power point tracking for dynamics of wind turbine system
Authors: Torchani Borhen , Azar Ahmad Taher , Ahmed Saim , Mahlous Ahmed Redha , Kasim Ibraheem Ibraheem
Published: August 2024

This article presents a proportional-integral sliding mode control (PI-SMC) approach for a two-mass variable speed wind turbine (VSWT) system. Most studies on wind turbines typically focus mainly on the electromagnetic part of the generators, or even on the high-speed part, considering the shaft stiffness as negligible. However, the generator torque is actually driven by the aerodynamic torque, and a two-mass system like the one studied here plays the role of a transmission element for this power. To address this challenge, the problem of low power generation resulting from wind speed variability is tackled by designing a PI-SMC control law, capable of controlling the mechanical turbine model that optimizes power and torque by tracking the maximum power point (MPPT) for rotational speed and aerodynamic power. To validate the developed theoretical results, an application of the wind turbine system is simulated in Matlab/Simulink, for a particular case. The control used is capable of satisfying the dynamic performance of the systems.
Plasma extracellular vesicle long RNA profiling identifies a predictive signature for immunochemotherapy efficacy in lung squamous cell carcinoma
Authors: Zhang Xin , Liao Jiatao , Yang Wenyue , Li Qiaojuan , Wang Zhen , Yu Hui , Wu Xianghua , Wang Huijie , Sun Si , Zhao Xinmin , Hu Zhihuang , Wang Jialei
Published: August 2024

Introduction

The introduction of Immune Checkpoint Inhibitors (ICIs) has marked a paradigm shift in treating Lung Squamous Cell Carcinoma (LUSC), emphasizing the urgent need for precise molecular biomarkers to reliably forecast therapeutic efficacy. This study aims to identify potential biomarkers for immunochemotherapy efficacy by focusing on plasma extracellular vesicle (EV)-derived long RNAs (exLRs).

Methods

We enrolled 78 advanced LUSC patients undergoing first-line immunochemotherapy. Plasma samples were collected, and exLR sequencing was conducted to establish baseline profiles. A retrospective analysis was performed on 42 patients to identify differentially expressed exLRs. Further validation of the top differentially expressed exLRs was conducted using quantitative reverse transcription PCR (qRT-PCR). Univariate Cox analysis was applied to determine the prognostic significance of these exLRs. Based on these findings, we developed a predictive signature (p-Signature).

Results

In the retrospective analysis of 42 patients, we identified 460 differentially expressed exLRs, with pathways related to leukocyte migration notably enriched among non-responders. Univariate Cox analysis revealed 45 exLRs with prognostic significance. The top 6 protein-coding exLRs were validated using qRT-PCR, identifying CXCL8, SSH3, and SDHAF1 as differentially expressed between responders and non-responders. The p-Signature, comprising these three exLRs, demonstrated high accuracy in distinguishing responders from non-responders, with an Area Under the Curve (AUC) of 0.904 in the retrospective cohort and 0.812 in the prospective cohort.

Discussion

This study highlighted the potential of plasma exLR profiles in predicting LUSC treatment efficacy. Intriguingly, lower p-Signature scores were associated with increased abundance of activated CD4+ and CD8+ T cells, indicating a more robust immune environment. These findings suggest that the p-Signature could serve as a valuable tool in guiding personalized and effective therapeutic strategies for LUSC.
Exercise-augmented THSD7B exhibited a positive prognostic implication and tumor-suppressed functionality in pan-cancer
Authors: Luo Zhiwen , Zhu Jinguo , Fang Zhengyuan , Xu Rui , Wan Renwen , He Yanwei , Chen Yisheng , Chen Shuo , Wang Qing , Liu Qizhi , Chen Shiyi
Published: August 2024

Background

Breast cancer, one of the most prevalent malignancies among women worldwide, has rising incidence rates. Physical activity, particularly exercise, has emerged as a significant modifier of cancer prognosis, influencing both tumor biology and patient outcomes.

Methods

In this study, we utilized a murine breast cancer model, dividing mice into a control group and an exercise group; the latter underwent 21 days of voluntary running. We conducted RNA sequencing, bioinformatics analysis, pan-cancer analysis, and cellular experiments to investigate the underlying mechanisms influenced by exercise.

Results

Exercise led to a significant reduction in tumor size and weight. Post-exercise mRNA sequencing indicated a notable upregulation of THSD7B in the exercised mice, with significant alterations observed in pathways such as MicroRNAs in cancers and the Calcium signaling pathway. In a broader cancer context, THSD7B showed considerable expression variability, being significantly downregulated in several cancers, correlating with positive prognostic outcomes in PRAD, LAML, KIRC, and GBM and highlighting its potential role as a prognostic marker and therapeutic target. THSD7B expression was also negatively associated with processes of breast cancer cell proliferation, migration, and invasion.

Conclusion

This study underscores the dual role of exercise in modulating gene expression relevant to tumor growth and highlights the potential of THSD7B as a therapeutic target in cancer. Future research should further explore the specific mechanisms by which exercise and THSD7B influence cancer progression and develop immunotherapy-enhanced strategies to change patient outcomes in clinical settings.
Seasonal and vertical tidal variability in the Southeastern Mediterranean Sea
Authors: Mantel Nadav , Feliks Yizhak , Gildor Hezi , Poulain Pierre-Marie , Mauri Elena , Menna Milena
Published: August 2024

Currents and pressure records from the DeepLev mooring station and drifter data in the eastern Levantine Basin were analyzed to identify the dominant tidal constituents and their seasonal and depth variability. Harmonic and spectral analysis of seasonal segments of currents and pressure reveal key attributes of the tidal regime: (1) dominant semidiurnal sea level variability; (2) seasonal variation of semidiurnal and diurnal tides in both currents and pressure datasets; and (3) significant diurnal currents with weak semidiurnal currents across all seasons. The most dominant tidal constituent from the pressure dataset is the M2 (12.4 h). Results from pressure datasets align with previous models and observations of semidiurnal tides. In contrast, the diurnal tides are larger than previously reported by 8—9 cm in the winter and 1—2 cm in the summer. The surface current tidal regime differs from prior reports in the eastern Levantine Basin, with M2 magnitudes weaker by 1 cm s-1, while the diurnal tides (K1, O1) are 1—2 cm s-1 larger. Seasonal segments showed seasonal differences in the local tidal regime’s amplitudes. The most pronounced seasonal differences were with the K1 and S2 tides, with differences between winter and fall of 7 cm for the K1 and 4 cm between summer and fall for the S2. We utilized the DeepLev datasets to compare a moored device with surface drifters near DeepLev by analyzing the M2 and S2 tides. Additionally, we examined data at different dataset lengths, considering the time constraints needed to resolve the tides adequately. Longer datasets improved the resolution of the tidal analysis and reduced amplitude leakages from nearby frequencies, resulting in a more realistic and accurate analysis of the tidal currents. Conversely, longer datasets resulted in fewer drifters remaining our study region for the allotted dataset length. From 32 available segments in 15 day dataset to 7 with a 30 day dataset, reducing the effectiveness of drifters as a local tidal research tool.
Causal roles of skin microbiota in skin cancers suggested by genetic study
Authors: Zhu Yuhang , Liu Wanguo , Wang Mei , Wang Xu , Wang Sibo
Published: August 2024

Background

There is evidence from observational studies that skin microbiota is linked to skin cancers. Nevertheless, the causal association between skin microbiota and skin cancers is yet to be fully clarified.

Methods

A bidirectional two-sample Mendelian randomization (MR) was performed to determine the causal relationship between skin microbiota and skin cancers. A total of 294 skin microbial taxa were identified from the first genome-wide association study across three skin microenvironments of two German population cohorts. Summary data of three skin cancers (malignant melanoma, squamous cell carcinoma, and basal cell carcinoma) were obtained from the FinnGen consortium. Moreover, sensitivity analysis examined horizontal pleiotropy and heterogeneity, and microenvironment-based meta-analysis confirmed the reliability of the results.

Results

We identified 65 nominal causalities and 5 strong causal associations between skin microbiota and skin cancers. Among them, the class Bacilli revealed a bidirectional positive relationship with malignant melanoma. The class Betaproteobacteria and class Gammaproteobacteria demonstrated a causal association with an elevated risk of malignant melanoma and basal cell carcinoma, respectively. In the reverse MR analysis, malignant melanoma was associated with a lower abundance of phylum Bacteroidetes. There were no indications of significant heterogeneity in instrumental variables or evidence of horizontal pleiotropy.

Conclusion

Our MR analysis indicated bidirectional causal associations between skin microbiota and skin cancers, and had the potential to offer novel perspectives on the mechanistic of microbiota-facilitated carcinogenesis.
The impact of altered dietary adenine concentrations on the gut microbiota in Drosophila
Authors: Yin Xianglin , Tong Qing , Wang Jingtao , Wei Jinfeng , Qin Zhenbo , Wu Yujie , Zhang Ruidi , Guan Baosheng , Qiu Hongbin
Published: August 2024

The gut microbiota influences host metabolism and health, impacting diseases. Research into how diet affects gut microbiome dynamics in model organisms is crucial but underexplored. Herein, we examined how dietary adenine affects uric acid levels and the gut microbiota over five generations of Drosophila melanogaster. Wild-type W1118 flies consumed diets with various adenine concentrations (GC: 0%, GL: 0.05%, and GH: 0.10%), and their gut microbiota were assessed via Illumina MiSeq sequencing. Adenine intake significantly increased uric acid levels in the GH group > the GC group. Despite no significant differences in the alpha diversity indices, there were significant disparities in the gut microbiota health index (GMHI) and dysbiosis index (MDI) among the groups. Adenine concentrations significantly altered the diversity and composition of the gut microbiota. High adenine intake correlated with increased uric acid levels and microbial population shifts, notably affecting the abundances of Proteobacteria and Firmicutes. The gut microbiota phenotypes included mobile elements, gram-positive bacteria, biofilm-forming bacteria, and gram-negative bacteria. The significantly enriched KEGG pathways included ageing, carbohydrate metabolism, and the immune system. In conclusion, adenine intake increases uric acid levels, alters gut microbiota, and affects KEGG pathways in Drosophila across generations. This study highlights the impact of dietary adenine on uric acid levels and the gut microbiota, providing insights into intergenerational nutritional effects.
Genome wide identification of the NPR1 gene family in plant defense mechanisms against biotic stress in chili (Capsicum annuum L.)
Authors: Ishfaqe Qandeel , Sami Adnan , Zeshan Haider Muhammad , Ahmad Arsalan , Shafiq Muhammad , Ali Qurban , Batool Alia , Haider Muhammad Saleem , Ali Daoud , Alarifi Saud , Islam Md Samiul , Manzoor Muhammad Aamir
Published: August 2024

Chili pepper cultivation in the Indian subcontinent is severely affected by viral diseases, prompting the need for environmentally friendly disease control methods. To achieve this, it is essential to understand the molecular mechanisms of viral resistance in chili pepper. The NONEXPRESSOR OF PATHOGENESIS-RELATED GENES 1 (NPR1) genes are known to provide broad-spectrum resistance to various phytopathogens by activating systemic acquired resistance (SAR). An in-depth understanding of NPR1 gene expression during begomovirus infection and its correlation with different biochemical and physiological parameters is crucial for enhancing resistance against begomoviruses in chili pepper. Nevertheless, limited information on chili CaNPR genes and their role in biotic stress constrains their potential in breeding for biotic stress resistance. By employing bioinformatics for genome mining, we identify 5 CaNPR genes in chili. The promoter regions of 1,500 bp of CaNPR genes contained cis-elements associated with biotic stress responses, signifying their involvement in biotic stress responses. Furthermore, these gene promoters harbored components linked to light, development, and hormone responsiveness, suggesting their roles in plant hormone responses and development. MicroRNAs played a vital role in regulating these five CaNPR genes, highlighting their significance in the regulation of chili genes. Inoculation with the begomovirus “cotton leaf curl Khokhran virus (CLCuKV)” had a detrimental effect on chili plant growth, resulting in stunted development, fibrous roots, and evident virus symptoms. The qRT-PCR analysis of two local chili varieties inoculated with CLCuKV, one resistant (V1) and the other susceptible (V2) to begomoviruses, indicated that CaNPR1 likely provides extended resistance and plays a role in chili plant defense mechanisms, while the remaining genes are activated during the early stages of infection. These findings shed light on the function of chili’s CaNPR in biotic stress responses and identify potential genes for biotic stress-resistant breeding. However, further research, including gene cloning and functional analysis, is needed to confirm the role of these genes in various physiological and biological processes. This in-silico analysis enhances our genome-wide understanding of how chili CaNPR genes respond during begomovirus infection.
Neural ageing and synaptic plasticity: prioritizing brain health in healthy longevity
Authors: Navakkode Sheeja , Kennedy Brian K.
Published: August 2024

Ageing is characterized by a gradual decline in the efficiency of physiological functions and increased vulnerability to diseases. Ageing affects the entire body, including physical, mental, and social well-being, but its impact on the brain and cognition can have a particularly significant effect on an individual’s overall quality of life. Therefore, enhancing lifespan and physical health in longevity studies will be incomplete if cognitive ageing is over looked. Promoting successful cognitive ageing encompasses the objectives of mitigating cognitive decline, as well as simultaneously enhancing brain function and cognitive reserve. Studies in both humans and animal models indicate that cognitive decline related to normal ageing and age-associated brain disorders are more likely linked to changes in synaptic connections that form the basis of learning and memory. This activity-dependent synaptic plasticity reorganises the structure and function of neurons not only to adapt to new environments, but also to remain robust and stable over time. Therefore, understanding the neural mechanisms that are responsible for age-related cognitive decline becomes increasingly important. In this review, we explore the multifaceted aspects of healthy brain ageing with emphasis on synaptic plasticity, its adaptive mechanisms and the various factors affecting the decline in cognitive functions during ageing. We will also explore the dynamic brain and neuroplasticity, and the role of lifestyle in shaping neuronal plasticity.
Association between the length of stay in rehabilitation and mortality among the adults with Parkinson’s disease: 2009–2019 Korean National Health Insurance Service Databases
Authors: Bae Suyeong , Hong Ickpyo , Baek Min Seok
Published: August 2024

Background

Rehabilitation is recognized as an effective means of alleviating the symptoms of Parkinson’s disease (PD) and improving the physical and cognitive functions of patients with PD. However, research often focuses on short-term outcomes such as functioning and quality of life. This study investigated the association between the length of stay in rehabilitation and mortality among patients with PD.

Methods

Using the Korean National Health Insurance Service database, we identified 636 participants diagnosed with PD who received rehabilitation. The main outcome was all-cause mortality. We used a Cox proportional hazards regression model to examine the relationship between length of stay in rehabilitation and mortality among patients with PD.

Results

The final sample comprised 374 females (58.81%) and 262 males (41.19%). A survival analysis revealed a significant association between the length of stay in rehabilitation and mortality, with a decrease in mortality of 16.1% in patients with PD who received one year of rehabilitation (hazard ratio = 0.839, 95% confidence interval = 0.788–0.895).

Conclusion

Our findings underscore the potential benefits of timely implementation of rehabilitative interventions in patients with PD and the need for comprehensive and long-term rehabilitation strategies. It also highlights the necessity of such services for patients with PD and the importance of developing patient-centered rehabilitation guidelines.
A neural basis for learning sequential memory in brain loop structures
Authors: Sihn Duho , Kim Sung-Phil
Published: August 2024

Introduction

Behaviors often involve a sequence of events, and learning and reproducing it is essential for sequential memory. Brain loop structures refer to loop-shaped inter-regional connection structures in the brain such as cortico-basal ganglia-thalamic and cortico-cerebellar loops. They are thought to play a crucial role in supporting sequential memory, but it is unclear what properties of the loop structure are important and why.

Methods

In this study, we investigated conditions necessary for the learning of sequential memory in brain loop structures via computational modeling. We assumed that sequential memory emerges due to delayed information transmission in loop structures and presented a basic neural activity model and validated our theoretical considerations with spiking neural network simulations.

Results

Based on this model, we described the factors for the learning of sequential memory: first, the information transmission delay should decrease as the size of the loop structure increases; and second, the likelihood of the learning of sequential memory increases as the size of the loop structure increases and soon saturates. Combining these factors, we showed that moderate-sized brain loop structures are advantageous for the learning of sequential memory due to the physiological restrictions of information transmission delay.

Discussion

Our results will help us better understand the relationship between sequential memory and brain loop structures.
Mesenchymal stem cells for peripheral nerve injury and regeneration: a bibliometric and visualization study
Authors: Aisaiti Aikebaierjiang , Aierxiding Shalayiding , Shoukeer Kutiluke , Muheremu Aikeremujiang
Published: August 2024

Objective

To use bibliometric methods to analyze the research hotspots and future development trends regarding the application of mesenchymal stem cells in peripheral nerve injury and regeneration.

Methods

Articles published from January 1, 2013, to December 31, 2023, were meticulously screened using the MeSH terms: TS = (“Mesenchymal stem cells” AND “Peripheral nerve injury”) OR TS = (“Mesenchymal stem cells” AND “Peripheral nerve regeneration”) within the Web of Science database. The compiled data was then subjected to in-depth analysis with the aid of VOSviewer and Cite Space software, which facilitated the identification of the most productive countries, organizations, authors, and the predominant keywords prevalent within this research domain.

Results

An extensive search of the Web of Science database yielded 350 relevant publications. These scholarly works were authored by 2,049 collaborative researchers representing 41 countries and affiliated with 585 diverse academic and research institutions. The findings from this research were disseminated across 167 various journals, and the publications collectively cited 21,064 references from 3,339 distinct journals.

Conclusion

Over the past decade, there has been a consistent upward trajectory in the number of publications and citations pertaining to the use of mesenchymal stem cells in the realm of peripheral nerve injury and regeneration. The domain of stem cell therapy for nerve injury has emerged as a prime focus of research, with mesenchymal stem cell therapy taking center stage due to its considerable promise in the treatment of nerve injuries. This therapeutic approach holds the potential to significantly enhance treatment options and rehabilitation prospects for patients suffering from such injuries.
Scheduled feeding improves sleep in a mouse model of Huntington’s disease
Authors: Chiem Emily , Zhao Kevin , Dell’Angelica Derek , Ghiani Cristina A. , Paul Ketema N. , Colwell Christopher S.
Published: August 2024

Sleep disturbances are common features of neurodegenerative disorders including Huntington’s disease (HD). Sleep and circadian disruptions are recapitulated in animal models, providing the opportunity to evaluate the effectiveness of circadian interventions as countermeasures for neurodegenerative disease. For instance, time restricted feeding (TRF) successfully improved activity rhythms, sleep behavior and motor performance in mouse models of HD. Seeking to determine if these benefits extend to physiological measures of sleep, electroencephalography (EEG) was used to measure sleep/wake states and polysomnographic patterns in male and female wild-type (WT) and bacterial artificial chromosome transgenic (BACHD) adult mice, under TRF and ad lib feeding (ALF). Our findings show that male, but not female, BACHD mice exhibited significant changes in the temporal patterning of wake and non-rapid eye movement (NREM) sleep. The TRF intervention reduced the inappropriate early morning activity by increasing NREM sleep in the male BACHD mice. In addition, the scheduled feeding reduced sleep fragmentation (# bouts) in the male BACHD mice. The phase of the rhythm in rapid-eye movement (REM) sleep was significantly altered by the scheduled feeding in a sex-dependent manner. The treatment did impact the power spectral curves during the day in male but not female mice regardless of the genotype. Sleep homeostasis, as measured by the response to six hours of gentle handling, was not altered by the diet. Thus, TRF improves the temporal patterning and fragmentation of NREM sleep without impacting sleep homeostasis. This work adds critical support to the view that sleep is a modifiable risk factor in neurodegenerative diseases.
Cancer-specific alterations in nuclear matrix proteins determined by multi-omics analyses of ductal carcinoma in situ
Authors: Almutairy Ali F. , Alhamed Abdullah S. , Grant Stephen G. , Falso Miranda J. , Day Billy W. , Simmons Colton R. , Latimer Jean J.
Published: August 2024

Introduction

Breast cancer (BC) is the most common cancer affecting women in the United States. Ductal carcinoma in situ (DCIS) is the earliest identifiable pre-invasive BC lesion. Estimates show that 14 to 50% of DCIS cases progress to invasive BC.

Methods

Our objective was to identify nuclear matrix proteins (NMP) with specifically altered expression in DCIS and later stages of BC compared to non-diseased breast reduction mammoplasty and a contralateral breast explant culture using mass spectrometry and RNA sequencing to accurately identify aggressive DCIS.

Results

Sixty NMPs were significantly differentially expressed between the DCIS and non-diseased breast epithelium in an isogenic contralateral pair of patient-derived extended explants. Ten of the sixty showed significant mRNA expression level differences that matched the protein expression. These 10 proteins were similarly expressed in non-diseased breast reduction cells. Three NMPs (RPL7A, RPL11, RPL31) were significantly upregulated in DCIS and all other BC stages compared to the matching contralateral breast culture and an unrelated non-diseased breast reduction culture. RNA sequencing analyses showed that these three genes were increasingly upregulated with BC progression. Finally, we identified three NMPs (AHNAK, CDC37 and DNAJB1) that were significantly downregulated in DCIS and all other BC stages compared to the isogenically matched contralateral culture and the non-diseased breast reduction culture using both proteomics and RNA sequencing techniques.

Discussion

These genes should form the basis of, or contribute to, a molecular diagnostic panel that could identify DCIS lesions likely to be indolent and therefore not requiring aggressive treatment.
Changes in optic nerve sheath diameter and its correlation with degree of consciousness, pupil diameter, and light reflex in children with central nervous system infection after osmotherapy
Authors: Rizqiamuti Anggia F. , Risan Nelly A. , Solek Purboyo , Hakim Dzulfikar D. L. , Nugraha Harry G. , Hawani Dewi , Dewi Mia M. , Herini Elisabeth S.
Published: August 2024

Background

High intracranial pressure (ICP) is one of the most common complications of central nervous system (CNS) infection. Failure to control high intracranial pressure results in brain herniation and death. One of the treatments for high ICP involves the administration of osmotherapy in the form of 3% NaCl or 20% mannitol with observation during administration. Observation of ICP during administration of osmotherapy is possible through measurement of optic nerve sheath diameter (ONSD), which could be correlated with degree of consciousness, pupil diameter, and light reflex. Previous studies have not correlated ONSD with degree of consciousness, pupil diameter, and light reflex during the administration of osmotherapy.

Purpose

To provide insights of incorporating ONSD measurement as a form of non-invasive bedside method for ICP monitoring by correlating it with degree of consciousness, pupil diameter, and light reflex at several time points.

Methods

This study is a prospective cohort study, performed at Dr. Hasan Sadikin General Central Hospital Bandung, Cibabat General Regional Hospital, and General Regional Hospital Bandung Kiwari on children aged 2–18 years with decreased consciousness and CNS infection, from June 2023. Inter-rater reliability was performed with a correlation coefficient of 0.90. Measurement of ONSD, degree of consciousness, pupil diameter, and light reflex simultaneously up to 48 h after initiation of osmotherapy to 30 patients. Correlational analyses were performed using Spearman's rank.

Results

Observation for 48 h after administration of osmotherapy showed changes in ONSD. A significant positive correlation was found between ONSD and degree of consciousness (r = 0.621 for the right eye and r = 0.602 for the left eye, p < 0.001). A significant positive correlation was found between ONSD and light reflex (r = 0.801 for the right eye and r = 0.812 for the left eye, p < 0.001). No significant correlation was found with changes of pupil diameter (r = −0.136 for the right eye and r = −0.141 for the left eye, p > 0.05).

Conclusion

A significant correlation was found between ONSD and degree of consciousness and light reflex in children aged 2–18 years with CNS infection during administration of osmotherapy.
Optimizing first-line TKI treatment efficacy in PD-L1-positive EGFR-mutated NSCLC: the impact of antiangiogenic agents
Authors: Jin Xuanhong , Pan Yang , Cheng Cheng , Shen Hangchen , Zhai Chongya , Yin Kailai , Zhu Xinyu , Pan Hongming , You Liangkun
Published: August 2024

Background

In individuals receiving treatment with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), those exhibiting positive PD-L1 expression might experience reduced progression-free survival (PFS). However, the effects on overall survival (OS) and the determination of efficacious treatment approaches are still not well-defined.

Methods

In our retrospective study, we examined data from 193 NSCLC patients with advanced EGFR mutations who received first-line TKI treatments, treated at two centers of Shaw Hospital in Zhejiang, China. This analysis covered a period from 1 January 2016 to 30 April 2023.

Results

Patients with PD-L1 positivity exhibited a markedly shorter average PFS (9.5 months versus 17.8 months, P < 0.001) and OS (44.4 months versus 65.7 months, P = 0.016) relative to those without PD-L1 expression. This difference in both PFS and OS remained statistically significant even after adjusting for multiple factors (P < 0.001 for PFS and P = 0.028 for OS). In the PD-L1-positive cohort, introducing combination antiangiogenic significantly extended both PFS (from 9.1 to 25.7 months, P = 0.026) and OS (from 42 to 53.5 months, P = 0.03). Post-first-line TKI therapy, 39.3% of PD-L1-positive patients and 54.5% of PD-L1-negative patients developed the T790M mutation (P = 0.212), with no notable difference in PFS from second-line TKI treatments between the groups. Additionally, subsequent combination therapy with immunotherapy markedly prolonged OS in the PD-L1-positive group. However, for PD-L1-negative patients, neither combination antiangiogenic therapy nor later-line immunotherapy demonstrated significant benefits in PFS or OS.

Conclusion

For PD-L1-positive patients, combined antiangiogenic treatments and immunotherapy can significantly improve survival outcomes. In contrast, PD-L1-negative patients show less benefit from these therapies, highlighting the greater efficacy of these treatments in PD-L1-positive individuals.
Real-world pharmacovigilance analysis of galsulfase: a study based on the FDA adverse event reporting system (FAERS) database
Authors: Li Shangze , Huang Runcheng , Meng Yuanyuan , Liu Yijia , Qian Jiao , Zou Junjie , Yang Jun
Published: August 2024

Background

Associated with enzyme deficiencies causing glycosaminoglycans (GAGs) accumulation, mucopolysaccharidosis type VI (MPS VI) is lysosomal storage disorder. In the treatment of MPS VI, galsulfase (Naglazyme) is commonly used as an enzyme replacement therapy (ERT). There remains a need for comprehensive real-world data on its safety and associated adverse events (AEs).

Objective

An analysis of the FDA Adverse Event Reporting System (FAERS) database will be conducted to identify potential risks and adverse reactions associated with galsulfase in real-life settings.

Methods

The FAERS database was used to extract data from Q2 2005 to Q4 2023. A total of 20,281,876 reports were analyzed after duplicate elimination, with 3,195 AE reports related to galsulfase identified. The association between galsulfase and AEs was investigated by utilizing four algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). The analysis focused on the timing of onset, signs of AEs, and clinical significance.

Results

Twenty seven organ systems were involved, and significant system organ classes (SOCs) included respiratory, thoracic and mediastinal disorders, and infections and infestations. At the PT level, 72 PTs corresponding to 15 SOCs were identified, with some AEs not previously mentioned in the product label. AEs associated with galsulfase had a median onset time of 1,471 days, with over half of the cases occurred within the first 5 years of treatment initiation.

Conclusion

This investigation delivers an exhaustive and indicative assessment of galsulfase’s safety profile, grounded in authentic, real-world evidence. The findings emphasis the importance of continuous safety surveillance and the emergence of new AEs. The identification of previously unreported urologic adverse events, such as glomerulonephritis membranous and nephritic syndrome, warrants further investigation. The study emphasizes the need for enhanced pharmacovigilance to ensure patient safety and the effectiveness of galsulfase treatment.
Commiphora myrrha n-hexane extract suppressed breast cancer progression through induction of G0/G1 phase arrest and apoptotic cell death by inhibiting the Cyclin D1/CDK4-Rb signaling pathway
Authors: Huang Huiming , Xie Jinxin , Wang Fei , Jiao Shungang , Li Xingxing , Wang Longyan , Liu Dongxiao , Wang Chaochao , Wei Xuejiao , Tan Peng , Tu Pengfei , Li Jun , Hu Zhongdong
Published: August 2024

Background

Breast cancer (BC) is one of the most frequently observed malignancies globally, yet drug development for BC has been encountering escalating challenges. Commiphora myrrha is derived from the dried resin of C. myrrha (T. Nees) Engl., and is widely adopted in China for treating BC. However, the anti-BC effect and underlying mechanism of C. myrrha remain largely unclear.

Methods

MTT assay, EdU assay, and colony formation were used to determine the effect of C. myrrha n-hexane extract (CMHE) on the proliferation of human BC cells. Cell cycle distribution and apoptosis were assessed via flow cytometry analysis. Moreover, metastatic potential was evaluated using wound-scratch assay and matrigel invasion assay. The 4T1 breast cancer-bearing mouse model was established to evaluate the anti-BC efficacy of CMHE in vivo. RNA-sequencing analysis, quantitative real-time PCR, immunoblotting, immunohistochemical analysis, RNA interference assay, and database analysis were conducted to uncover the underlying mechanism of the anti-BC effect of CMHE.

Results

We demonstrated the significant inhibition in the proliferative capability of BC cell lines MDA-MB-231 and MCF-7 by CMHE. Moreover, CMHE-induced G0/G1 phase arrest and apoptosis of the above two BC cell lines were also observed. CMHE dramatically repressed the metastatic potential of these two cells in vitro. Additionally, the administration of CMHE remarkably suppressed tumor growth in 4T1 tumor–bearing mice. No obvious toxic or side effects of CMHE administration in mice were noted. Furthermore, immunohistochemical (IHC) analysis demonstrated that CMHE treatment inhibited the proliferative and metastatic abilities of cancer cells, while also promoting apoptosis in the tumor tissues of mice. Based on RNA sequencing analysis, quantitative real-time PCR, immunoblotting, and IHC assay, the administration of CMHE downregulated Cyclin D1/CDK4-Rb signaling pathway in BC. Furthermore, RNA interference assay and database analysis showed that downregulated Cyclin D1/CDK4 signaling cascade participated in the anti-BC activity of CMHE.

Conclusion

CMHE treatment resulted in the suppression of BC cell growth through the stimulation of cell cycle arrest at the G0/G1 phase and the induction of apoptotic cell death via the inhibition of the Cyclin D1/CDK4-Rb pathway, thereby enhancing the anti-BC effect of CMHE. CMHE has potential anti-BC effects, particularly in those harboring aberrant activation of Cyclin D1/CDK4-Rb signaling.
On the ignition of H11B fusion fuel
Authors: Ghorbanpour Esmat , Belloni Fabio
Published: August 2024

We have revisited recent results on the ideal ignition of H11B fuel, in the light of the latest available reactivity, an alternative self-consistent calculation of the electron temperature, an increased extent of the suprathermal effects and the impact of plasma density. At high density, we find that the ideal ignition temperature is appreciably relaxed (e.g., Ti≃150 keV for ni∼1026 cm−3 and an optimal 11B/H concentration ε=0.15) and burn becomes substantial. We have then investigated central hot-spot ignition in both isobaric and isochoric inertial confinement configurations. Although implosion-driven ignition appears to be unfeasible, the isochoric self-heating conditions foster favourable preliminary conclusions on the utilization of proton fast ignition. In the isochoric case, we find a broad minimum in the ignition energy at ρR≃8.5 g/cm2 and 220≲Ti≲340 keV (80 ≲Te≲95 keV), for ε=0.15.
Building a network with assortative mixing starting from preference functions, with application to the spread of epidemics
Authors: Romanescu Razvan G.
Published: August 2024

Compartmental models of disease spread have been well studied on networks built according to the Configuration Model, i.e., where the degree distribution of individual nodes is specified, but where connections are made randomly. Dynamics of spread on such “first order” networks were shown to be profoundly different compared to epidemics under the traditional mass action assumption. Assortativity, i.e., the preferential mixing of nodes according to degree, is a second order property that is thought to impact epidemic trajectory. We first show how assortative mixing can come about from individual preferences to connect with others of lower or higher degree, and propose an algorithm for constructing such a network. We then investigate via simulation how this network structure favors or inhibits diffusion processes, such as the spread of an infectious disease.
Vicious cycle of oxidative stress and neuroinflammation in pathophysiology of chronic vascular encephalopathy
Authors: Dmytriv Tetiana R. , Duve Khrystyna V. , Storey Kenneth B. , Lushchak Volodymyr I.
Published: August 2024

Chronic vascular encephalopathy (CVE) is a frequent cause of vascular mild cognitive impairment and dementia, which significantly worsens the quality of life, especially in the elderly population. CVE is a result of chronic cerebral hypoperfusion, characterized by prolonged limited blood flow to the brain. This causes insufficient oxygenation of the brain leading to hypoxia. The latter can trigger a series of events associated with the development of oxidative/reductive stresses and neuroinflammation. Addressing the gap in knowledge regarding oxidative and reductive stresses in the development of vascular disorders and neuroinflammation can give a start to new directions of research in the context of CVE. In this review, we consider the hypoxia-induced molecular challenges involved in the pathophysiology of CVE, focusing on oxidative stress and neuroinflammation, which are combined in a vicious cycle of neurodegeneration. We also briefly describe therapeutic approaches to the treatment of CVE and outline the prospects for the use of sulforaphane, an isothiocyanate common in cruciferous plants, and vitamin D to break the vicious cycle and alleviate the cognitive impairments characteristic of patients with CVE.
Rethinking treatment failures. Research on a group of Italian psychotherapists
Authors: Oasi Osmano , De Salve Francesca , Rossi Chiara , Maggio Simone , Casabona Ilaria , Molgora Sara
Published: August 2024

Introduction

Psychotherapeutic failures involve situational, relational, and personal factors. Dropout refers to a patient’s unilateral termination of treatment without the therapist’s knowledge or approval. Premature termination occurs when therapy is discontinued before achieving a sufficient reduction in initial problems.

Objective

This study explores the role of therapist’s emotional response (countertransference), gender, psychotherapeutic orientation, and patient diagnosis in the context of psychotherapeutic failures.

Method

A mixed-method approach was used. Fifty-nine Italian psychotherapists, practicing mostly privately with at least 5 years of experience, were recruited through Italian professional internet websites. The Therapist Response Questionnaire and the Impasse Interview were administered to each psychotherapist. Each therapist was asked to reflect on their last dropout patient. Quantitative (MANOVA) and qualitative analyses (textual content analysis) were conducted with SPSS and T-LAB, respectively.

Results

The quantitative analyses revealed that the most frequent countertransference response was Helpless/Inadequate, with female therapists experiencing this more frequently than male therapists. The qualitative analyses identified two main factors explaining most of the variance in countertransference responses: Parental/Protective versus Hostile/Angry, and Positive/Satisfying versus Helpless/Inadequate, with Helpless/Inadequate central. Additionally, the qualitative analysis of treatment interruption methods revealed two factors explaining over 50% of the variance. Lack of communication was linked to negative themes, while mediated and direct communication were associated with positive terms. Direct communication was characterized as useful, while mediated communication was linked to dropout and attachment figures.

Conclusion

Under pressure, psychotherapists’ anxiety levels increase, often managed ambivalently or avoidantly. These results suggest that awareness of psychotherapist emotional responses is important to limit psychotherapeutic failures. These findings offer valuable insights for clinical practice.