bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating carbon sequestration potential and optimizing management strategies for Moso bamboo (Phyllostachys pubescens) forests using machine learning
Authors: Lv Shaofeng , Yuan Ning , Sun Xiaobo , Chen Xin , Shi Yongjun , Zhou Guomo , Xu Lin
Published: April 2024

Estimating the carbon sequestration potential of Moso bamboo (Phyllostachys pubescens) forests and optimizing management strategies play pivotal roles in enhancing quality and promoting sustainable development. However, there is a lack of methods to simulate changes in carbon sequestration capacity in Moso bamboo forests and to screen and optimize the best management measures based on long-term time series data from fixed-sample fine surveys. Therefore, this study utilized continuous survey data and climate data from fixed sample plots in Zhejiang Province spanning from 2004 to 2019. By comparing four different algorithms, namely random forest, support vector machine, XGBoost, and BP neural network, to construct aboveground carbon stock models for Moso bamboo forests. The ultimate goal was to identify the optimal algorithmic model. Additionally, the key driving parameters for future carbon stocks were considered and future aboveground carbon stocks were predicted in Moso bamboo forests. Then formulated an optimal management strategy based on these predictions. The results indicated that the carbon stock model constructed using the XGBoost algorithm, with an R2 of 0.9895 and root mean square error of 0.1059, achieved the best performance and was considered the optimal algorithmic model. The most influential driving parameters for vegetation carbon stocks in Moso bamboo forests were found to be mean age, mean diameter at breast height, and mean culm density. Under optimal management measures, which involve no harvesting of 1–3 du bamboo, 30% harvesting of 4 du bamboo, and 80% harvesting of bamboo aged 5 du and above. Our predictions show that aboveground carbon stocks in Moso bamboo forests in Zhejiang Province will peak at 36.25 ± 8.47 Tg C in 2046 and remain stable from 2046 to 2060. Conversely, degradation is detrimental to the long-term maintenance of carbon sequestration capacity in Moso bamboo forests, resulting in a peak aboveground carbon stock of 29.50 ± 7.49 Tg C in 2033, followed by a continuous decline. This study underscores the significant influence of estimating carbon sequestration potential and optimizing management decisions on enhancing and sustaining the carbon sequestration capacity of Moso bamboo forests.
Breaking the maternity mold: navigating the return to work and challenging rigid maternal beliefs through an online psychological intervention
Authors: Rapisarda Sebastiano , De Carlo Alessandro , Pasqualetto Elena , Volling Brenda L. , Dal Corso Laura
Published: April 2024

Working mothers must often balance work and family responsibilities which can be affected by rigid and irrational beliefs about motherhood. The present study had two aims: (a) to provide psychometric evidence for a shortened Italian version of the Rigid Maternal Beliefs Scale (RMBS) and (b) to facilitate mothers’ return to work after maternity leave by reducing perceptions of anxiety and stress related to rigid maternal beliefs (i.e., perceptions and societal expectations of mothers, maternal confidence, maternal dichotomy) and by teaching specific recovery strategies (e.g., relaxation, mastery experiences) to manage anxiety and stress through an online psychological intervention. Results replicated the three-factor structure of the original RMBS and showed good psychometric properties. The online psychological intervention resulted in decrease in the rigidity of maternal beliefs, perceived anxiety and stress, and increase in recovery strategies. These initial results are promising and encourage further investigation into online psychological interventions for improving the well-being of working mothers.
A novel dual mechanism-of-action bispecific PD-1-IL-2v armed by a “βγ-only” interleukin-2 variant
Authors: Jiang Yongji , Chen Chuyuan , Liu Yuan , Wang Rong , Feng Chuan , Cai Lili , Chang Shuang , Zhao Lei
Published: April 2024

Introduction

Interleukin-2 (IL-2) is one of the first cytokines to be discovered as an immune agonist for cancer immunotherapy. Biased IL-2 variants had been discovered to eliminate Treg activation or enhance the tumor specific T cell cytotoxicity. However, all the biased IL-2 variants pose the risk to overstimulate immune response at a low-dose range. Here, we introduce a novel dual-MOA bispecific PD-1-IL-2v molecule with great anti-tumor efficacy in a high dosed manner.

Methods

The novel IL-2 variant was designed by structural truncation and shuffling. The single armed bispecific PD-1-IL-2v molecule and IL-2v were studied by immune cell activations in vitro and in vivo and anti-tumor efficacy in mouse model.

Results and discussion

The IL-2 variant in this bispecific antibody only binds to IL-2Rβγ complex in a fast-on/off manner without α, β or γ single receptor binding. This IL-2v mildly activates T and NK cells without over stimulation, meanwhile it diminishes Treg activation compared to the wild type IL-2. This unique bispecific molecule with “βγ-only” IL-2v can not only “in-cis” stimulate and expand CD8 T and NK cells moderately without Treg activation, but also block the PD-1/L1 interaction at a similar dose range with monoclonal antibody.
Endoplasmic reticulum stress: bridging inflammation and obesity-associated adipose tissue
Authors: Ma Kaile , Zhang Yanjiao , Zhao Jingyi , Zhou Lijuan , Li Min
Published: April 2024

Obesity presents a significant global health challenge, increasing the susceptibility to chronic conditions such as diabetes, cardiovascular disease, and hypertension. Within the context of obesity, lipid metabolism, adipose tissue formation, and inflammation are intricately linked to endoplasmic reticulum stress (ERS). ERS modulates metabolism, insulin signaling, inflammation, as well as cell proliferation and death through the unfolded protein response (UPR) pathway. Serving as a crucial nexus, ERS bridges the functionality of adipose tissue and the inflammatory response. In this review, we comprehensively elucidate the mechanisms by which ERS impacts adipose tissue function and inflammation in obesity, aiming to offer insights into targeting ERS for ameliorating metabolic dysregulation in obesity-associated chronic diseases such as hyperlipidemia, hypertension, fatty liver, and type 2 diabetes.
Impaired meningeal lymphatic drainage in Listeria monocytogenes infection
Authors: Feng Jian , Ren Yuanzhen , Wang Xilin , Li Xiaojing , Zhu Xingguo , Zhang Baokai , Zhao Qi , Sun Xiaochen , Tian Xinxin , Liu Hongyang , Dong Fan , Li Xiu-Li , Qi Linlin , Wei Bin
Published: April 2024

Previous studies have demonstrated an association between lymphatic vessels and diseases caused by bacterial infections. Listeria monocytogenes (LM) bacterial infection can affect multiple organs, including the intestine, brain, liver and spleen, which can be fatal. However, the impacts of LM infection on morphological and functional changes of lymphatic vessels remain unexplored. In this study, we found that LM infection not only induces meningeal and mesenteric lymphangiogenesis in mice, but also impairs meningeal lymphatic vessels (MLVs)-mediated macromolecules drainage. Interestingly, we found that the genes associated with lymphatic vessel development and function, such as Gata2 and Foxc2, were downregulated, suggesting that LM infection may affect cellular polarization and valve development. On the other hand, photodynamic ablation of MLVs exacerbated inflammation and bacterial load in the brain of mice with LM infection. Overall, our findings indicate that LM infection induces lymphangiogenesis and may affect cell polarization, cavity formation, and valve development during lymphangiogenesis, ultimately impairing MLVs drainage.
Bruton’s tyrosine kinase inhibition limits endotoxic shock by suppressing IL-6 production by marginal zone B cells in mice
Authors: Kawata Kazuhiko , Hatano Shinya , Baba Akemi , Imabayashi Keisuke , Baba Yoshihiro
Published: April 2024

Sepsis is a systemic inflammatory response to a severe, life-threatening infection with organ dysfunction. Although there is no effective treatment for this fatal illness, a deeper understanding of the pathophysiological basis of sepsis and its underlying mechanisms could lead to the development of new treatment approaches. Here, we demonstrate that the selective Bruton’s tyrosine kinase (Btk) inhibitor acalabrutinib augments survival rates in a lipopolysaccharide (LPS)-induced septic model. Our in vitro and in vivo findings both indicate that acalabrutinib reduces IL-6 production specifically in marginal zone B (MZ B) cells rather than in macrophages. Furthermore, Btk-deficient MZ B cells exhibited suppressed LPS-induced IL-6 production in vitro. Nuclear factor-kappa B (NF-κB) signaling, which is the downstream signaling cascade of Toll-like receptor 4 (TLR4), was also severely attenuated in Btk-deficient MZ B cells. These findings suggest that Btk blockade may prevent sepsis by inhibiting IL-6 production in MZ B cells. In addition, although Btk inhibition may adversely affect B cell maturation and humoral immunity, antibody responses were not impaired when acalabrutinib was administered for a short period after immunization with T-cell-independent (TI) and T-cell-dependent (TD) antigens. In contrast, long-term administration of acalabrutinib slightly impaired humoral immunity. Therefore, these findings suggest that Btk inhibitors may be a potential option for alleviating endotoxic shock without compromising humoral immunity and emphasize the importance of maintaining a delicate balance between immunomodulation and inflammation suppression.
The diverse roles of insulin signaling in insect behavior
Authors: Weger Anastasia A. , Rittschof Clare C.
Published: April 2024

In insects and other animals, nutrition-mediated behaviors are modulated by communication between the brain and peripheral systems, a process that relies heavily on the insulin/insulin-like growth factor signaling pathway (IIS). Previous studies have focused on the mechanistic and physiological functions of insulin-like peptides (ILPs) in critical developmental and adult milestones like pupation or vitellogenesis. Less work has detailed the mechanisms connecting ILPs to adult nutrient-mediated behaviors related to survival and reproductive success. Here we briefly review the range of behaviors linked to IIS in insects, from conserved regulation of feeding behavior to evolutionarily derived polyphenisms. Where possible, we incorporate information from Drosophila melanogaster and other model species to describe molecular and neural mechanisms that connect nutritional status to behavioral expression via IIS. We identify knowledge gaps which include the diverse functional roles of peripheral ILPs, how ILPs modulate neural function and behavior across the lifespan, and the lack of detailed mechanistic research in a broad range of taxa. Addressing these gaps would enable a better understanding of the evolution of this conserved and widely deployed tool kit pathway.
The impact of interactions between various systems caused by three consecutive years of La Nina events on the abnormal summer high temperatures in China in 2022
Authors: Boyu Chai
Published: April 2024

In the summer of 2022, like in many other regions of the world, an unprecedented period of continuous high-temperature weather occurred in eastern China. The degree and duration of this event far exceeded normal standards. Between 2020 and 2022, the tropical Pacific experienced the most significant three-year consecutive La Nina event recorded in recent decades. We investigate linkages between these events: the high-temperature response in eastern China and Asia under the background of such La Nina events. Development of summer La Nina events contributed to a high-temperature heat wave during the summer of 2022. Rapid development of these events in the third year exacerbated negative Indian Ocean Dipole phases because of energy accumulation from abnormal easterly winds. The combined effects of the negative Indian Ocean Dipole phase and La Nina provided background field support that strengthened the West Pacific Subtropical High (WPSH) and the Iranian High, leading to high terrestrial temperature anomalies. An empirical orthogonal function (EOF) analysis of the vertical velocity in the middle and low latitudes of the tropical Indian Ocean and the Asian continent reveals the first two empirical orthogonal function modes to be conducive to the strengthening of Walker circulation in 2022. These two main modes jointly reflect the rising movement of the equatorial East Indian Ocean and South China Sea in 2022, and the sinking movement to the west of the Tibet Plateau and eastern China, which was conducive to generating high temperatures in eastern China. Finally, the South Asian High was affected by the La Nina event that lasted for three years, showing a strong trend towards the north, thus making an important contribution to this high temperature.
Investigation into the seamless construction for hundred-meter scale super-length raft structure based on magnesia expansive agent concrete
Authors: Han Bin , Wang Huichao , Liao Hong , Dai Chao , Zhao Yunpeng , Xu Wenlong , Zhou Guojing , Shi Chuandong
Published: April 2024

This research introduces an innovative construction method based on magnesia expansive agent concrete for the seamless construction of hundred-meter scale super-length raft structures, corroborated by the on-site test. The basic principle of this construction method is to use the pre compression stress generated by magnesia expansive agent to offset temperature and shrinkage stress. A temperature-strain monitoring system was employed to gather data, affirming the technique’s applicability and safety. Through the examination of temperature and strain dispersion trends in super-length raft structure, recommendations for the configuration of temperature-strain sensors have been put forth. Through the scrutiny of the temporal evolution pattern of temperature, the specific temporal and spatial coordinates that warrant particular vigilance during the surveillance of the raft’s inner-surface temperature difference were identified. Upon evaluating the correlation between strain dispersion and strain-temperature differential in the raft’s thickness dimension, a novel temperature control index (the bottom-surface temperature difference) was introduced. The threshold for this metric was established at 30°C, derived from empirical test outcomes conducted on-site. Furthermore, the critical regions for monitoring the bottom-surface temperature difference were specified.
Genomic characterization and outbreak investigations of methicillin-resistant Staphylococcus aureus in a county-level hospital in China
Authors: Huang Linyao , Zhu Liangrong , Yan Jianxin , Lin Yajing , Ding Ding , He Long , Li Yexuzi , Ying Yi , Shen Lijiong , Jiang Yuhan , Cai Haijun , Jiang Tian
Published: April 2024

Methicillin-resistant Staphylococcus aureus (MRSA) is a common pathogen contributing to healthcare-associated infections, which can result in multiple sites infections. The epidemiological characteristics of MRSA exhibit variability among distinct regions and healthcare facilities. The aim of this study was to investigate the molecular epidemiology and nosocomial outbreak characteristics of MRSA in a county-level hospital in China. A total of 130 non-repetitive MRSA strains were collected from December 2020 to November 2021. Whole-genome sequencing (WGS) was performed to identify antimicrobial resistance and virulence factors. Phylogenetic analysis was conducted to ascertain genetic diversity and phylogenetic relationships. Independent transmission scenarios were determined by the phylogeny derived from single nucleotide polymorphisms (SNPs) within the core genome. All the MRSA isolates were collected from the intensive care unit (30.00%, 39/130), the department of otorhinolaryngology (10.00%, 13/130) and the department of burn unit (9.23%, 12/130). The clinical samples mainly included phlegm (53.85%, 70/130), purulent fluid (24.62%, 32/130), and secretions (8.46%, 11/130). The resistance rates to erythromycin, clindamycin and ciprofloxacin were 75.38, 40.00, and 39.23%, respectively. All the isolates belonged to 11 clonal complexes (CCs), with the major prevalent types were CC5, CC59, and CC398, accounting for 30.00% (39/130), 29.23% (38/130), and 16.92% (22/130), respectively. Twenty sequence types (STs) were identified, and ST59 (25.38%, 33/130) was the dominant lineage, followed by ST5 (23.84%, 31/130) and ST398 (16.92%, 22/130). Three different SCCmec types were investigated, most of isolates were type IV (33.85%, 44/130), followed by type II (27.69%, 36/130) and type III (0.77%, 1/130). The common clonal structures included CC5-ST5-t2460-SCCmec IIa, CC59-ST59-t437-SCCmec IV and CC398-ST398-t034-SCCmec (−), with rates of 16.92% (22/130), 14.62% (19/130), and 13.84% (18/130), respectively. Only 12 panton-valentine leucocidin (PVL) positive strains were identified. Two independent clonal outbreaks were detected, one consisting of 22 PVL-negative strains belongs to CC5-ST5-t2460-SCCmec IIa and the other consisting of 8 PVL-negative strains belongs to CC5-ST5-t311-SCCmec IIa. Overall, our study indicated that the CC5 lineage emerged as the predominant epidemic clone of MRSA, responsible for nosocomial outbreaks and transmission within a county-level hospital in China, highlighting the necessity to strengthen infection control measures for MRSA in such healthcare facilities.
Chemoinformatics and machine learning techniques to identify novel inhibitors of the lemur tyrosine kinase-3 receptor involved in breast cancer
Authors: Alrumaihi Faris
Published: April 2024

Breast cancer is still the largest cause of cancer death in women, and around 70% of primary breast cancer patients are estrogen receptor (ER)-positive, which is the most frequent kind of breast cancer. The lemur tyrosine kinase-3 (LMTK3) receptor has been linked to estrogen responsiveness in breast cancer. However, the function of LMTK3 in reaction to cytotoxic chemotherapy has yet to be studied. Breast cancer therapy research remains tricky due to a paucity of structural investigations on LMTK3. We performed structural investigations on LMTK3 using molecular docking and molecular dynamics (MD) simulations of the LMTK3 receptor in complex with the top three inhibitor molecules along with a control inhibitor. Analysis revealed the top three compounds show the best binding affinities during docking simulations. Interactive analysis of hydrogen bonds inferred hotspot residues Tyr163, Asn138, Asp133, Tyr56, Glu52, Ser132, Asp313, and Asp151. Some other residues in the 5-Å region determined strong alkyl bonds and conventional hydrogen bond linkages. Furthermore, protein dynamics analysis revealed significant modifications among the top complexes and the control system. There was a transition from a loop to a-helix conformation in the protein–top1 complex, and in contrast, in complexes top2 and top3, the formation of a stabilizing sheet in the C chain was observed, which limited significant mobility and increased complex stability. Significant structural alterations were observed in the protein–top complexes, including a shorter helix region and the creation of some loop regions in comparison to the control system. Interestingly, binding free energies, including MMGB/PBSA WaterSwap analysis estimation, reveals that the top1 complex system was more stable than other systems, especially in comparison to the control inhibitor complex system. These results suggest a the plausible mode of action for the novel inhibitors. Therefore, the current investigation contributes to understanding the mechanism of action, serving as a basis for future experimental studies.
Abnormal cell sorting and altered early neurogenesis in a human cortical organoid model of Protocadherin-19 clustering epilepsy
Authors: Niu Wei , Deng Lu , Mojica-Perez Sandra P. , Tidball Andrew M. , Sudyk Roksolana , Stokes Kyle , Parent Jack M.
Published: April 2024

Introduction

Protocadherin-19 (PCDH19)-Clustering Epilepsy (PCE) is a developmental and epileptic encephalopathy caused by loss-of-function variants of the PCDH19 gene on the X-chromosome. PCE affects females and mosaic males while male carriers are largely spared. Mosaic expression of the cell adhesion molecule PCDH19 due to random X-chromosome inactivation is thought to impair cell–cell interactions between mutant and wild type PCDH19-expressing cells to produce the disease. Progress has been made in understanding PCE using rodent models or patient induced pluripotent stem cells (iPSCs). However, rodents do not faithfully model key aspects of human brain development, and patient iPSC models are limited by issues with random X-chromosome inactivation.

Methods

To overcome these challenges and model mosaic PCDH19 expression in vitro, we generated isogenic female human embryonic stem cells with either HA-FLAG-tagged PCDH19 (WT) or homozygous PCDH19 knockout (KO) using genome editing. We then mixed GFP-labeled WT and RFP-labeled KO cells and generated human cortical organoids (hCOs).

Results

We found that PCDH19 is highly expressed in early (days 20–35) WT neural rosettes where it co-localizes with N-Cadherin in ventricular zone (VZ)-like regions. Mosaic PCE hCOs displayed abnormal cell sorting in the VZ with KO and WT cells completely segregated. This segregation remained robust when WT:KO cells were mixed at 2:1 or 1:2 ratios. PCE hCOs also exhibited altered expression of PCDH19 (in WT cells) and N-Cadherin, and abnormal deep layer neurogenesis. None of these abnormalities were observed in hCOs generated by mixing only WT or only KO (modeling male carrier) cells.

Discussion

Our results using the mosaic PCE hCO model suggest that PCDH19 plays a critical role in human VZ radial glial organization and early cortical development. This model should offer a key platform for exploring mechanisms underlying PCE-related cortical hyperexcitability and testing of potential precision therapies.
Multi-layer CNN-LSTM network with self-attention mechanism for robust estimation of nonlinear uncertain systems
Authors: Liu Lin , Feng Jun , Li Jiwei , Chen Wanxin , Mao Zhizhong , Tan Xiaowei
Published: April 2024

Introduction

With the help of robot technology, intelligent rehabilitation of patients with lower limb motor dysfunction caused by stroke can be realized. A key factor constraining the clinical application of rehabilitation robots is how to realize pattern recognition of human movement intentions by using the surface electromyography (sEMG) sensors to ensure unhindered human-robot interaction.

Methods

A multilayer CNN-LSTM prediction network incorporating the self-attention mechanism (SAM) is proposed, in this paper, which can extract and learn the periodic and trend characteristics of the sEMG signals, and realize the accurate autoregressive prediction of the human motion information. Firstly, the multilayer CNN-LSTM network utilizes the CNN layer for initial feature extraction of data, and the LSTM network is used to improve the enhancement of the historical time-series features. Then, the SAM is used to improve the global feature extraction performance and parallel computation speed of the network.

Results

In comparison with existing test is carried out using actual data from five healthy subjects as well as a clinical hemiplegic patient to verify the superiority and practicality of the proposed algorithm. The results show that most of the model’s prediction R > 0.9 for different motion states of healthy subjects; in the experiments oriented to the motion characteristics of patient subjects, the angle prediction results of R > 0.99 for the untrained data on the affected side, which proves that our proposed model also has a better effect on the angle prediction of the affected side.

Discussion

The main contribution of this paper is to realize continuous motion estimation of ankle joint for healthy and hemiplegic individuals under non-ideal conditions (weak sEMG signals, muscle fatigue, high muscle tension, etc.), which improves the pattern recognition accuracy and robustness of the sEMG sensor-based system.
Mutations in the postsynaptic density signaling hub TNIK disrupt PSD signaling in human models of neurodevelopmental disorders
Authors: Jiang Jianzhi , Wilkinson Brent , Flores Ilse , Hartel Nicolas , Mihaylov Simeon R. , Clementel Veronica A. , Flynn Helen R. , Alkuraya Fowsan S. , Ultanir Sila , Graham Nicholas A. , Coba Marcelo P.
Published: April 2024

A large number of synaptic proteins have been recurrently associated with complex brain disorders. One of these proteins, the Traf and Nck interacting kinase (TNIK), is a postsynaptic density (PSD) signaling hub, with many variants reported in neurodevelopmental disorder (NDD) and psychiatric disease. While rodent models of TNIK dysfunction have abnormal spontaneous synaptic activity and cognitive impairment, the role of mutations found in patients with TNIK protein deficiency and TNIK protein kinase activity during early stages of neuronal and synapse development has not been characterized. Here, using hiPSC-derived excitatory neurons, we show that TNIK mutations dysregulate neuronal activity in human immature synapses. Moreover, the lack of TNIK protein kinase activity impairs MAPK signaling and protein phosphorylation in structural components of the PSD. We show that the TNIK interactome is enriched in NDD risk factors and TNIK lack of function disrupts signaling networks and protein interactors associated with NDD that only partially overlap to mature mouse synapses, suggesting a differential role of TNIK in immature synapsis in NDD.
Cannabinoid type-1 receptor signaling in dopaminergic Engrailed-1 expressing neurons modulates motivation and depressive-like behavior
Authors: Baddenhausen Sarah , Lutz Beat , Hofmann Clementine
Published: April 2024

The endocannabinoid system comprises highly versatile signaling functions within the nervous system. It is reported to modulate the release of several neurotransmitters, consequently affecting the activity of neuronal circuits. Investigations have highlighted its roles in numerous processes, including appetite-stimulating characteristics, particularly for palatable food. Moreover, endocannabinoids are shown to fine-tune dopamine-signaled processes governing motivated behavior. Specifically, it has been demonstrated that excitatory and inhibitory inputs controlled by the cannabinoid type 1 receptor (CB1) regulate dopaminergic neurons in the mesocorticolimbic pathway. In the present study, we show that mesencephalic dopaminergic (mesDA) neurons in the ventral tegmental area (VTA) express CB1, and we investigated the consequences of specific deletion of CB1 in cells expressing the transcription factor Engrailed-1 (En1). To this end, we validated a new genetic mouse line EN1-CB1-KO, which displays a CB1 knockout in mesDA neurons beginning from their differentiation, as a tool to elucidate the functional contribution of CB1 in mesDA neurons. We revealed that EN1-CB1-KO mice display a significantly increased immobility time and shortened latency to the first immobility in the forced swim test of adult mice. Moreover, the maximal effort exerted to obtain access to chocolate-flavored pellets was significantly reduced under a progressive ratio schedule. In contrast, these mice do not differ in motor skills, anhedonia- or anxiety-like behavior compared to wild-type littermates. Taken together, these findings suggest a depressive-like or despair behavior in an inevitable situation and a lack of motivation to seek palatable food in EN1-CB1-KO mice, leading us to propose that CB1 plays an important role in the physiological functions of mesDA neurons. In particular, our data suggest that CB1 directly modifies the mesocorticolimbic pathway implicated in depressive-like/despair behavior and motivation. In contrast, the nigrostriatal pathway controlling voluntary movement seems to be unaffected.
Stearidonic acid improves eicosapentaenoic acid status: studies in humans and cultured hepatocytes
Authors: Seidel Ulrike , Eberhardt Katharina , Wiebel Michelle , Luersen Kai , Ipharraguerre Ignacio R. , Haegele Franziska A. , Winterhalter Peter , Bosy-Westphal Anja , Schebb Nils Helge , Rimbach Gerald
Published: April 2024

Background

Ahiflower oil from the seeds of Buglossoides arvensis is rich in α-linolenic acid (ALA) and stearidonic acid (SDA). ALA and SDA are potential precursor fatty acids for the endogenous synthesis of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are n3-long chain polyunsaturated fatty acids (n3-LC-PUFAS), in humans. Since taurine, an amino sulfonic acid, is often associated with tissues rich in n3-LC-PUFAS (e.g., in fatty fish, human retina), taurine may play a role in EPA- and DHA-metabolism.

Objective

To examine the capacity of the plant-derived precursor fatty acids (ALA and SDA) and of the potential fatty acid metabolism modulator taurine to increase n3-LC-PUFAS and their respective oxylipins in human plasma and cultivated hepatocytes (HepG2 cells).

Methods

In a monocentric, randomized crossover study 29 healthy male volunteers received three sequential interventions, namely ahiflower oil (9 g/day), taurine (1.5 g/day) and ahiflower oil (9 g/day) + taurine (1.5 g/day) for 20 days. In addition, cultivated HepG2 cells were treated with isolated fatty acids ALA, SDA, EPA, DHA as well as taurine alone or together with SDA.

Results

Oral ahiflower oil intake significantly improved plasma EPA levels (0.2 vs. 0.6% of total fatty acid methyl esters (FAMES)) in humans, whereas DHA levels were unaffected by treatments. EPA-levels in SDA-treated HepG2 cells were 65% higher (5.1 vs. 3.0% of total FAMES) than those in ALA-treated cells. Taurine did not affect fatty acid profiles in human plasma in vivo or in HepG2 cells in vitro. SDA-rich ahiflower oil and isolated SDA led to an increase in EPA-derived oxylipins in humans and in HepG2 cells, respectively.

Conclusion

The consumption of ahiflower oil improves the circulating levels of EPA and EPA-derived oxylipins in humans. In cultivated hepatocytes, EPA and EPA-derived oxylipins are more effectively increased by SDA than ALA.
Macrophage colony-stimulating factor and its role in the tumor microenvironment: novel therapeutic avenues and mechanistic insights
Authors: Yi Li , Gai Yihan , Chen Zhuo , Tian Kecan , Liu Pengfei , Liang Hongrui , Xu Xinyu , Peng Qiuyi , Luo Xiaoqing
Published: April 2024

The tumor microenvironment is a complex ecosystem where various cellular and molecular interactions shape the course of cancer progression. Macrophage colony-stimulating factor (M-CSF) plays a pivotal role in this context. This study delves into the biological properties and functions of M-CSF in regulating tumor-associated macrophages (TAMs) and its role in modulating host immune responses. Through the specific binding to its receptor colony-stimulating factor 1 receptor (CSF-1R), M-CSF orchestrates a cascade of downstream signaling pathways to modulate macrophage activation, polarization, and proliferation. Furthermore, M-CSF extends its influence to other immune cell populations, including dendritic cells. Notably, the heightened expression of M-CSF within the tumor microenvironment is often associated with dismal patient prognoses. Therefore, a comprehensive investigation into the roles of M-CSF in tumor growth advances our comprehension of tumor development mechanisms and unveils promising novel strategies and approaches for cancer treatment.
Profiling of serum metabolome of breast cancer: multi-cancer features discriminate between healthy women and patients with breast cancer
Authors: Mrowiec Katarzyna , Debik Julia , Jelonek Karol , Kurczyk Agata , Ponge Lucyna , Wilk Agata , Krzempek Marcela , Giskeødegård Guro F. , Bathen Tone F. , Widłak Piotr
Published: April 2024

Introduction

The progression of solid cancers is manifested at the systemic level as molecular changes in the metabolome of body fluids, an emerging source of cancer biomarkers.

Methods

We analyzed quantitatively the serum metabolite profile using high-resolution mass spectrometry. Metabolic profiles were compared between breast cancer patients (n=112) and two groups of healthy women (from Poland and Norway; n=95 and n=112, respectively) with similar age distributions.

Results

Despite differences between both cohorts of controls, a set of 43 metabolites and lipids uniformly discriminated against breast cancer patients and healthy women. Moreover, smaller groups of female patients with other types of solid cancers (colorectal, head and neck, and lung cancers) were analyzed, which revealed a set of 42 metabolites and lipids that uniformly differentiated all three cancer types from both cohorts of healthy women. A common part of both sets, which could be called a multi-cancer signature, contained 23 compounds, which included reduced levels of a few amino acids (alanine, aspartate, glutamine, histidine, phenylalanine, and leucine/isoleucine), lysophosphatidylcholines (exemplified by LPC(18:0)), and diglycerides. Interestingly, a reduced concentration of the most abundant cholesteryl ester (CE(18:2)) typical for other cancers was the least significant in the serum of breast cancer patients. Components present in a multi-cancer signature enabled the establishment of a well-performing breast cancer classifier, which predicted cancer with a very high precision in independent groups of women (AUC>0.95).

Discussion

In conclusion, metabolites critical for discriminating breast cancer patients from controls included components of hypothetical multi-cancer signature, which indicated wider potential applicability of a general serum metabolome cancer biomarker.
Partnering Early to Provide for Infants At Risk of Cerebral Palsy (PĒPI ARC): protocol for a feasibility study of a regional hub for early detection of cerebral palsy in Aotearoa New Zealand
Authors: Allermo Fletcher Angelica , Kilgour Gaela , Sandle Meghan , Kidd Sally , Sheppard Alison , Swallow Stephanie , Stott Ngaire Susan , Battin Malcolm , Korent Wyllis , Williams Sian A.
Published: April 2024

Introduction

Cerebral palsy (CP) can now be diagnosed in infants with identified CP risk factors as early as three months of age; however, many barriers prevent equitable access to early detection pathways. The “Partnering Early to Provide for Infants At Risk of Cerebral Palsy” feasibility study (PĒPI ARC) seeks to trial a new approach to decrease inequitable health service in Aotearoa New Zealand for high-risk infants and their families. PĒPI ARC incorporates face-to-face clinics, an in-person and virtual Hub, and the use of telehealth to enable flexible access to CP assessments and support for health professionals in early CP detection.

Methods and analysis

A non-randomised feasibility study was conducted from a tertiary Neonatal Intensive Care Unit (NICU) in Wellington and included seven regional referral centres, servicing nearly 30% of the total population in New Zealand (NZ). The families of infants with a high risk of neurodevelopmental impairment and health professionals interacting with the Hub were invited to participate. Mixed methods were used to evaluate the (i) equitable implementation of an early detection pathway, (ii) acceptability, (iii) demand among families and health professionals, (iv) efficacy in relation to reducing the age of receipt of CP diagnosis, and (v) the experiences around communication and information sharing.

Ethics and dissemination

The NZ Health and Disability Ethics Committee approved this study (HDEC: 2022 FULL 13434). The findings will be disseminated in peer-reviewed journals, in conference presentations, and via professional networks.

Clinical trial registration

Australian New Zealand Clinical Trials Registry: ACTRN12623000600640.
Low-dose and standard-dose whole-body [18F]FDG-PET/CT imaging: implications for healthy controls and lung cancer patients
Authors: Ferrara Daria , Shiyam Sundar Lalith Kumar , Chalampalakis Zacharias , Geist Barbara Katharina , Gompelmann Daniela , Gutschmayer Sebastian , Hacker Marcus , Kertész Hunor , Kluge Kilian , Idzko Marco , Langsteger Werner , Yu Josef , Rausch Ivo , Beyer Thomas
Published: April 2024

Aim: High-sensitivity hybrid positron emission tomography (PET) imaging using advanced whole-body (WB) or total-body PET/computed tomography (CT) systems permits reducing injected tracer activity while preserving diagnostic quality. Such approaches are promising for healthy control studies or exploring inter-organ communication in systemic diseases. This study assessed test/retest variations in the fluoro-2-deoxy-D-glucose (FDG) uptake in key organs from low-dose (LD) and standard-dose (STD) [18F]FDG-PET/CT imaging protocols in healthy controls and lung cancer patients.

Methods: A total of 19 healthy controls (19–62 years, 46–104 kg, 10 M/9 F) and 7 lung cancer patients (47–77 years, 50–88 kg, 4 M/3 F) underwent [18F]FDG-PET/CT imaging. All subjects were first injected (“test,” LD) with 28 ± 2 MBq FDG and underwent a dynamic (0–67 min post-injection) WB imaging protocol with LD-CT. Then, 90 min post-LD injection, the subjects were repositioned and injected with 275 ± 16 MBq FDG (“retest,” STD). Second LD-CT and STD-CT scans were acquired for healthy controls and patients, respectively. Static images (55–67 min post-injection) were considered for subsequent analysis. The CT images were used to automatically segment the target volumes of interest. Standardized uptake values normalized to the body weight (SUVBW) were extracted for each volume of interest. The mean SUVBW were compared for both LD/STD conditions with paired t-tests. In patients, FDG-avid lesions were manually delineated on LD and STD static images. Effective dose levels were estimated from both the CT and PET acquisitions.

Results: Organ-based mean SUVBW were similar between the LD and STD (mean %difference ≤5%) in both healthy controls and cancer patients, except in the heart. Intra-control test/retest variability was significant in the brain, heart, and skeletal muscle (p < 0.05). While 17 lesions were delineated on the STD images of the patients, only 10/17 lesions were identified on the LD images due to increased image noise. Lesion-based mean SUVBW were similar between LD and STD acquisitions (p = 0.49, %difference = 10%). In patients, the effective doses were (1.9 ± 0.2) mSv (LD-CT), (16.6 ± 5.4) mSv (STD-CT), (0.5 ± 0.1) mSv (LD-PET), and (4.6 ± 0.3) mSv (STD-PET).

Conclusion: LD and STD [18F]FDG injections in healthy controls and lung cancer patients yielded comparable mean SUVBW, except in the heart. Dose levels may be reduced for [18F]FDG-PET imaging without a loss in mean SUVBW accuracy, promoting LD-PET/CT protocols for studying multi-organ metabolic patterns. In oncology patients, this approach may be hindered by a lower diagnostic quality in the presence of significant noise.
Wearable device for continuous sweat lactate monitoring in sports: a narrative review
Authors: Yang Geonwoo , Hong Junggi , Park Seung-Bo
Published: April 2024

In sports science, the use of wearable technology has facilitated the development of new approaches for tracking and assessing athletes’ performance. This narrative review rigorously explores the evolution and contemporary state of wearable devices specifically engineered for continuously monitoring lactate levels in sweat, an essential biomarker for appraising endurance performance. Lactate threshold tests have traditionally been integral in tailoring training intensity for athletes, but these tests have relied on invasive blood tests that are impractical outside a laboratory setting. The transition to noninvasive, real-time monitoring through wearable technology introduces an innovative approach, facilitating continuous assessment without the constraints inherent in traditional methodologies. We selected 34 products from a pool of 246 articles found through a meticulous search of articles published up to January 2024 in renowned databases: PubMed, Web of Science, and ScienceDirect. We used keywords such as “sweat lactate monitoring,” “continuous lactate monitoring,” and “wearable devices.” The findings underscore the capabilities of noninvasive sweat lactate monitoring technologies to conduct long-term assessments over a broad range of 0–100 mM, providing a safer alternative with minimal infection risks. By enabling real-time evaluations of the lactate threshold (LT) and maximal lactate steady state (MLSS), these technologies offer athletes various device options tailored to their specific sports and preferences. This review explores the mechanisms of currently available lactate monitoring technologies, focusing on electrochemical sensors that have undergone extensive research and show promise for commercialization. These sensors employ amperometric reactions to quantify lactate levels and detect changes resulting from enzymatic activities. In contrast, colorimetric sensors offer a more straightforward and user-friendly approach by displaying lactate concentrations through color alterations. Despite significant advancements, the relationship between sweat lactate and blood lactate levels remains intricate owing to various factors such as environmental conditions and the lag between exercise initiation and sweating. Furthermore, there is a marked gap in research on sweat lactate compared to blood lactate across various sports disciplines. This review highlights the need for further research to address these shortcomings and substantiate the performance of lactate sweat monitoring technologies in a broader spectrum of sports environments. The tremendous potential of these technologies to supplant invasive blood lactate tests and pioneer new avenues for athlete management and performance optimization in real-world settings heralds a promising future for integrating sports science and wearable technology.
Neuroscientific results of experimental studies on the control of acute pain with hypnosis and suggested analgesia
Authors: Miltner Wolfgang H. R. , Franz Marcel , Naumann Ewald
Published: April 2024

This narrative review summarizes a representative collection of electrophysiological and imaging studies on the neural processes and brain sources underlying hypnotic trance and the effects of hypnotic suggestions on the processing of experimentally induced painful events. It complements several reviews on the effect of hypnosis on brain processes and structures of chronic pain processing. Based on a summary of previous findings on the neuronal processing of experimentally applied pain stimuli and their effects on neuronal brain structures in healthy subjects, three neurophysiological methods are then presented that examine which of these neuronal processes and structures get demonstrably altered by hypnosis and can thus be interpreted as neuronal signatures of the effect of analgesic suggestions: (A) On a more global neuronal level, these are electrical processes of the brain that can be recorded from the cranial surface of the brain with magnetoencephalography (MEG) and electroencephalography (EEG). (B) On a second level, so-called evoked (EPs) or event-related potentials (ERPs) are discussed, which represent a subset of the brain electrical parameters of the EEG. (C) Thirdly, imaging procedures are summarized that focus on brain structures involved in the processing of pain states and belong to the main imaging procedures of magnetic resonance imaging (MRI/fMRI) and positron emission tomography (PET). Finally, these different approaches are summarized in a discussion, and some research and methodological suggestions are made as to how this research could be improved in the future.
Physical activity on prescription for children with obesity: a focus group study exploring experiences in paediatric healthcare
Authors: Boman Charlotte , Bernhardsson Susanne , Lundqvist Stefan , Melin Karin , Lauruschkus Katarina
Published: April 2024

Background

Insufficient physical activity is a growing public health concern and is closely linked to obesity in both adults and children. Swedish physical activity on prescription (PAP) is effective in increasing physical activity levels in adults, but knowledge about how PAP is used in paediatric healthcare is lacking. Therefore, this study aimed to explore experiences of working with PAP for children with obesity amongst paediatric staff and managers.

Methods

Seven focus group discussions with 26 participants from paediatric outpatient clinics in western Sweden were conducted. Data were analysed both inductively and deductively, framed by the Normalization Process Theory's four core constructs: coherence, cognitive participation, collective action, and reflexive monitoring.

Results

The PAP work for children with obesity was experienced to be about helping children to become physically active, and less about losing weight. Identified barriers for using PAP were the non-uniform nature of the work and a perceived lack of guidelines. Collaboration with physiotherapists and physical activity organisers outside the organisation was identified as an important facilitator. An important contextual factor for implementing PAP is the collaboration between paediatric clinics and physical activity organisers. In the transition between these stakeholders, maintaining a family-centred approach when working with PAP was experienced as challenging.

Conclusions

PAP is a well-known intervention that is inconsistently used for children with obesity. The intervention should include a family-centred approach for this patient group. It also needs to align better with existing collaborations with other healthcare units as well as with new forms of collaboration with physical activity organisers in the community.
Assessing the usability of aromatic mouthwashes in alleviating physiological stress responses
Authors: Dilrukshi E. A. Chayani , Ogino Tatsuki , Ishikawa Mami , Kuroda Hiroki , Nomura Shusaku
Published: April 2024

Background

Mouthwashes play a pivotal role in oral care, and their efficacy has been explored extensively across various dimensions. As a contribution to the development of novel oral care products, this study aims to investigate the psychophysiological effects of aromatic mouthwashes during the resilience period from a short-term cognitive stressor utilizing biological signals and subjective evaluations.

Methods

A within-participant experimental design with 22 healthy females was conducted with four mouthwashes; peppermint (Mint), peppermint + bergamot (MB), peppermint + sweet orange (MO), and peppermint + lavender (ML), and water as the control (Ctl), after a 20-min calculation task. Subjective evaluations and physiological responses including skin conductance level and electrocardiogram were recorded throughout the experiment.

Results

Citrus mouthwashes (MO and MB) showed a greater decrease in heart rate and a significant increase in the high-frequency component of heart rate variability. The participants indicated a significant effect in terms of “flavor preference” and “refreshing sensation” for mouthwash use compared to the Ctl.

Conclusion

The results suggest that rinsing with citrus-flavored mouthwashes has a positive impact in alleviating the physiological stress response (in terms of cardiac activity). These findings may have implications for the development of innovative, novel oral care products that promote stress reduction and improve oral health.
Fact or Fable: Your Guide to Fighting Misinformation
Authors: Dijkstra Katinka , Mollenbrok Arwen Sienna Divera , Nguyen Giang Thi Quynh , Cijntje Guieane Elaiza
Published: April 2024

Nobody wants to believe false information and share it with others. Still, at some point, almost everyone will consider some fake news reports to be true, without even realizing it. This may happen because the information matches their world view but also because news producers use clever tricks to spread misinformation. In this article, we provide you with the tools to understand what misinformation is, why you may fall for it, and how to fight it. Given the ease with which fake news spreads on social media, it is important to know what you can do to resist its power.