bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of blood flow restriction exercise on N-lactoylphenylalanine and appetite regulation in obese adults: a cross-design study
Authors: Li Shuoqi , Guo Rong , Wang Juncheng , Zheng Xinyu , Zhao Shuo , Zhang Zhiru , Yu Wenbing , Li Shiming , Zheng Peng
Published: December 2023

Background

N-lactoylphenylalanine (Lac-Phe) is a new form of “exerkines” closely related to lactate (La), which may be able to inhibit appetite. Blood flow restriction (BFR) can lead to local tissue hypoxia and increase lactate accumulation. Therefore, this study investigated the effects of combining Moderate-intensity Continuous Exercise (MICE) with BFR on Lac-Phe and appetite regulation in obese adults.

Methods

This study employed the cross-design study and recruited 14 obese adults aged 18-24 years. The participants were randomly divided into three groups and performed several tests with specific experimental conditions: (1) M group (MICE without BFR, 60%VO2max, 200 kJ); (2) B group (MICE with BFR, 60%VO2max, 200 kJ); and (3) C group (control session without exercise). Participants were given a standardized meal 60 min before exercise and a ad libitum 60 min after exercise. In addition, blood and Visual Analogue Scale (VAS) were collected before, immediately after, and 1 hour after performing the exercise.

Results

No significant difference in each index was detected before exercise. After exercise, the primary differential metabolites detected in the M and B groups were xanthine, La, succinate, Lac-Phe, citrate, urocanic acid, and myristic acid. Apart from that, the major enrichment pathways include the citrate cycle, alanine, aspartate, and glutamate metabolism. The enhanced Lac-Phe and La level in the B group was higher than M and C groups. Hunger of the B group immediately after exercise substantially differed from M group. The total ghrelin, glucagon-like peptide-1 and hunger in the B group 1 hour after exercise differed substantially from M group. The results of calorie intake showed no significant difference among the indexes in each group.

Conclusions

In conclusion, this cross-design study demonstrated that the combined MICE and BFR exercise reduced the appetite of obese adults by promoting the secretion of Lac-Phe and ghrelin. However, the exercise did not considerably affect the subsequent ad libitum intake.
Endogenous and microbial biomarkers for periodontitis and type 2 diabetes mellitus
Authors: Li Songjun , Li Hongwen , Kong Haiying , Wu Shang Ying , Cheng Chak Kwong , Xu Jian
Published: December 2023

It has been well documented that there is a two-way relationship between diabetes mellitus and periodontitis. Diabetes mellitus represents an established risk factor for chronic periodontitis. Conversely, chronic periodontitis adversely modulates serum glucose levels in diabetic patients. Activated immune and inflammatory responses are noted during diabetes and periodontitis, under the modulation of similar biological mediators. These activated responses result in increased activity of certain immune-inflammatory mediators including adipokines and microRNAs in diabetic patients with periodontal disease. Notably, certain microbes in the oral cavity were identified to be involved in the occurrence of diabetes and periodontitis. In other words, these immune-inflammatory mediators and microbes may potentially serve as biomarkers for risk assessment and therapy selection in diabetes and periodontitis. In this review, we briefly provide an updated overview on different potential biomarkers, providing novel diagnostic and therapeutic insights on periodontal complications and diabetes mellitus.
Cellular plasticity facilitates phenotypic change in a dominant coral’s Symbiodiniaceae assemblage
Authors: Anthony Colin J. , Lock Colin , Taylor Brett M. , Bentlage Bastian
Published: December 2023

Coral-associated dinoflagellates (Symbiodiniaceae) are photosynthetic endosymbionts that influence coral acclimation, as indicated by photo-endosymbiotic phenotypic variance across different environmental conditions. Symbiont shuffling (shifts in endosymbiont community composition), changes in endosymbiont cell density, and cellular plasticity have all been proposed as acclimation mechanisms. However, few studies have been able to partition which of the three strategies were responsible for observed phenotypic variance. Using a combination of metabarcoding and flow cytometry, we simultaneously characterized Acropora pulchra-associated Symbiodiniaceae assemblages at the community, population, and individual level under natural environmental conditions to deduce whether seasonal phenotypic change and site-related phenotypic variation of Symbiodiniaceae assemblages is a product of symbiont shuffling or cellular plasticity. Symbiodiniaceae assemblages displayed season-specific phenotypic variance, while Symbiodiniaceae community composition was geographically structured and cell density showed limited data structure. Based on these patterns, we reveal that cellular plasticity of Symbiodiniaceae was the source of a phenotypic variation, thus indicating that cellular plasticity is a mechanism for acclimation to mild environmental change.
Targeting NAD+ metabolism: dual roles in cancer treatment
Authors: Yong Jiaxin , Cai Songqing , Zeng Zhaolei
Published: December 2023

Nicotinamide adenine dinucleotide (NAD+) is indispensable for various oxidation-reduction reactions in mammalian cells, particularly during energy production. Malignant cells increase the expression levels of NAD+ biosynthesis enzymes for rapid proliferation and biomass production. Furthermore, mounting proof has indicated that NAD-degrading enzymes (NADases) play a role in creating the immunosuppressive tumor microenvironment (TME). Interestingly, both inhibiting NAD+ synthesis and targeting NADase have positive implications for cancer treatment. Here we summarize the detrimental outcomes of increased NAD+ production, the functions of NAD+ metabolic enzymes in creating an immunosuppressive TME, and discuss the progress and clinical translational potential of inhibitors for NAD+ synthesis and therapies targeting NADase.
Macrophages and platelets in liver fibrosis and hepatocellular carcinoma
Authors: Casari Martina , Siegl Dominik , Deppermann Carsten , Schuppan Detlef
Published: December 2023

During fibrosis, (myo)fibroblasts deposit large amounts of extracellular matrix proteins, thereby replacing healthy functional tissue. In liver fibrosis, this leads to the loss of hepatocyte function, portal hypertension, variceal bleeding, and increased susceptibility to infection. At an early stage, liver fibrosis is a dynamic and reversible process, however, from the cirrhotic stage, there is significant progression to hepatocellular carcinoma. Both liver-resident macrophages (Kupffer cells) and monocyte-derived macrophages are important drivers of fibrosis progression, but can also induce its regression once triggers of chronic inflammation are eliminated. In liver cancer, they are attracted to the tumor site to become tumor-associated macrophages (TAMs) polarized towards a M2- anti-inflammatory/tumor-promoting phenotype. Besides their role in thrombosis and hemostasis, platelets can also stimulate fibrosis and tumor development by secreting profibrogenic factors and regulating the innate immune response, e.g., by interacting with monocytes and macrophages. Here, we review recent literature on the role of macrophages and platelets and their interplay in liver fibrosis and hepatocellular carcinoma.
Overview of anti-viral effects of probiotics via immune cells in pre-, mid- and post-SARS-CoV2 era
Authors: Kanauchi Osamu , Low Zhao Xuan , Jounai Kenta , Tsuji Ryohei , AbuBakar Sazaly
Published: December 2023

The COVID-19 outbreak has caused significant global changes and increased public awareness of SARS-CoV-2. Substantial progress in developing vaccines, enhancing sanitation practices, and implementing various measures to combat the virus, including the utilization of probiotics has been made. This comprehensive review examined the medical impact of clinically proven probiotics on infectious diseases, considering three crucial time periods: before (pre-), during (mid-), and after (post-) COVID-19 pandemic era. This review also showed a perspective on the use of probiotics to stimulate the innate immune system and prevent infectious diseases. In pre-COVID-19 era, several probiotic strains were found to be clinically effective in addressing gastrointestinal infectious diseases, the common cold and flu. However, the mechanism by which probiotics exerted their antiviral effects remained relatively unclear during that period. Nevertheless, probiotics, Lactococcus lactis strain Plasma (LC-Plasma), and others have gained attention for their unique ability to modulate the immune system and demonstrate antiviral properties. While some probiotics have shown promise in alleviating gastrointestinal symptoms linked to COVID-19, their direct effectiveness in treating or preventing COVID-19 progression has not yet been conclusively established. As we transition into the post-COVID-19 era, the relationship between COVID-19 and plasmacytoid dendritic cells (pDCs), a vital component of the innate immune system, has been gradually elucidated. These findings are now being applied in developing novel vaccines and treatments involving interferons and in immune activation research using probiotics as adjuvants, comparable to CpG-DNA through TLR9. The role of the local innate immune system, including pDCs, as the first line of defense against viral infections has gained increasing interest. Moving forward, insight of the immune system and the crosstalk between probiotics and the innate immune system is expected to highlight the role of probiotics in adjunctive immunoregulatory therapy. In combination with drug treatments, probiotics may play a more substantial role in enhancing immune responses. The immunoregulatory approach using probiotics such as LC-Plasma, which can induce anti-infectious factors such as interferons, holds promise as a viable therapeutic and prophylactic option against viral infectious diseases due to their good safety profile and protective efficacy.
Case Report: ISG15 deficiency caused by novel variants in two families and effective treatment with Janus kinase inhibition
Authors: Burleigh Alice , Moraitis Elena , Al Masroori Eman , Al-Abadi Eslam , Hong Ying , Omoyinmi Ebun , Titheradge Hannah , Stals Karen , Jones Wendy D. , Gait Anthony , Jayarajan Vignesh , Di Wei-Li , Sebire Neil , Solman Lea , Ogboli Malobi , Welch Steven B. , Sudarsanam Annapurna , Wacogne Ian , Price-Kuehne Fiona , Jensen Barbara , Brogan Paul A. , Eleftheriou Despina
Published: December 2023

ISG15 deficiency is a rare disease caused by autosomal recessive variants in the ISG15 gene, which encodes the ISG15 protein. The ISG15 protein plays a dual role in both the type I and II interferon (IFN) immune pathways. Extracellularly, the ISG15 protein is essential for IFN-γ-dependent anti-mycobacterial immunity, while intracellularly, ISG15 is necessary for USP18-mediated downregulation of IFN-α/β signalling. Due to this dual role, ISG15 deficiency can present with various clinical phenotypes, ranging from susceptibility to mycobacterial infection to autoinflammation characterised by necrotising skin lesions, intracerebral calcification, and pulmonary involvement. In this report, we describe novel variants found in two different families that result in complete ISG15 deficiency and severe skin ulceration. Whole exome sequencing identified a heterozygous missense p.Q16X ISG15 variant and a heterozygous multigene 1p36.33 deletion in the proband from the first family. In the second family, a homozygous total ISG15 gene deletion was detected in two siblings. We also conducted further analysis, including characterisation of cytokine dysregulation, interferon-stimulated gene expression, and p-STAT1 activation in lymphocytes and lesional tissue. Finally, we demonstrate the complete and rapid resolution of clinical symptoms associated with ISG15 deficiency in one sibling from the second family following treatment with the Janus kinase (JAK) inhibitor baricitinib.
Shell microstructures (disturbance lines) of Arctica islandica (Bivalvia): a potential proxy for severe oxygen depletion
Authors: Höche Nils , Zettler Michael L. , Huang Xizhi , Schöne Bernd R.
Published: December 2023

The spread of oxygen deficiency in nearshore coastal habitats endangers benthic communities. To better understand the mechanisms leading to oxygen depletion and eventually hypoxia, predict the future development of affected ecosystems, and define suitable mitigation strategies requires detailed knowledge of the dissolved oxygen (DO) history. Suitable high-resolution DO archives covering coherent time intervals of decades to centuries include bivalve shells. Here, we explored if the microstructure, specifically disturbance lines, in shells of Arctica islandica from the Baltic Sea can be used as an alternative or complementary proxy to Mn/Cashell to track the frequency and severity of past low-DO events. Disturbance lines differ from periodic annual growth lines by the presence of fine complex crossed lamellae instead of irregular simple prisms. Aside from a qualitative assessment of microstructural changes, the morphology of individual biomineral units (BMUs) was quantitatively determined by artificial intelligence-assisted image analysis to derive models for DO reconstruction. As demonstrated, Mn-rich disturbance lines can provide a proxy for past deoxygenation events (i.e., DO < 45 µmol/L), but it currently remains unresolved if low DO leads to microstructurally distinct features that differ from those caused by other environmental stressors. At least in studied specimens from the Baltic Sea and Iceland, low temperature, salinity near the lower physiological tolerance, or food scarcity did not result in disturbance lines. With decreasing DO supply, disturbance lines seem to become more prominent, contain more Mn, and consist of increasingly smaller and more elongated BMUs with a larger perimeter-to-area ratio. Although the relationship between DO and BMU size or elongation was statistically significant, the explained variability (<1.5%) was too small and the error too large to reconstruct DO values. BMU parameters may reveal a closer relationship with DO if studied in three dimensions and if the DO content was determined at high resolution, directly at the position where the bivalves lived, something that future work should address.
Non-technical skills and teamwork in trauma: from the emergency department to the operating room
Authors: Alexandrino Henrique , Martinho Bárbara , Ferreira Luís , Baptista Sérgio
Published: December 2023

Management of a trauma patient is a challenging process. Swift and accurate clinical assessment is required and time-sensitive decisions and life-saving procedures must be performed in an unstable patient. This requires a coordinated response by both the emergency room (ER) and operating room (OR) teams. However, a team of experts does not necessarily make an expert team. Root cause analysis of adverse events in surgery has shown that failures in coordination, planning, task management and particularly communication are the main causes for medical errors. While most research is focused on the ER trauma team, the trauma OR team also deserves attention. In fact, OR team dynamics may resemble more the ER team than the elective OR team. ER and OR trauma teams assemble on short notice, and their members, who are from different specialties and backgrounds, may not train regularly together or even know each other beforehand. And yet, they have to perform high-risk procedures and make high stake decisions, in a time-sensitive manner. The airline industry has long recognized the role of team training and non-technical skills (NTS) in reducing hazards. The implementation of the so called crew resource management or crisis resource management (CRM) has significantly made airline travel safer and the transposition to the medical context, with specific training in non-technical skills, has also brought great benefits. In fact, it is clear that adoption of non-technical skills (NTS) in healthcare has led to an increase in patient safety. In this narrative review we recapitulate some of the key non-technical skills and their relevance in trauma, with a focus on both the emergency department (ER) and the operating room (OR) teams, as well as on the transition of care from one to the other. Also, we explore the use of debriefing the team, as well as the roles of NTS training in both undergraduate and postgraduate settings. We review some of the existing trauma training courses and their roles in developing NTS. Finally, we briefly address the challenges posed by the development of trauma hybrid operating rooms.
Enterococcus species: insights into antimicrobial resistance and whole-genome features of isolates recovered from livestock and raw meat in Ghana
Authors: Amuasi Grebstad Rabbi , Dsani Esther , Owusu-Nyantakyi Christian , Owusu Felicia A. , Mohktar Quaneeta , Nilsson Pernille , Adu Bright , Hendriksen Rene S. , Egyir Beverly
Published: December 2023

Introduction

Enterococcus spp. have gradually evolved from commensals to causing life-threatening hospital-acquired infections globally due to their inherent antimicrobial resistance ability and virulence potential. Enterococcus spp. recovered from livestock and raw meat samples were characterized using antimicrobial susceptibility testing and whole-genome sequencing.

Materials and methods

Isolates were confirmed using the MALDI-ToF mass spectrometer, and antimicrobial susceptibility was determined using the Kirby-Bauer disk diffusion method. Whole genome sequencing was performed on isolates resistant to two or more antibiotics. Bioinformatics analysis was performed to determine sequence types, resistance and virulence gene content and evolutionary relationships between isolates from meat and livestock samples, and other enterococci genomes curated by PATRIC. eBURST analysis was used to assign genomes to clonal complexes.

Results

Enterococcus spp. were predominantly E. faecalis (96/236; 41%) and E. faecium (89/236; 38%). Overall, isolates showed resistance to erythromycin (78/236; 33%), tetracycline (71/236; 30%), ciprofloxacin (20/236; 8%), chloramphenicol (12/236; 5%), linezolid (7/236; 3%), ampicillin (4/236; 2%) and vancomycin (1/236, 0.4%). Resistance to two or more antimicrobial agents was detected among 17% (n = 40) Enterococcus spp. Resistance genes for streptogramins [lsa(A), lsa(E), msr(C)], aminoglycosides [aac(6′)-Ii, aph(3′)-III, ant(6)-Ia, aac(6′)-aph(2″), str], amphenicol [cat], macrolides [erm(B), erm(T), msr(C)], tetracyclines [tet(M), tet(L), tet(S)] and lincosamides [lsa(A), lsa(E), lnu(B)] were detected among the isolates. Genes for biofilm formation, adhesins, sex pheromones, cytolysins, hyaluronidase, oxidative stress resistance, quorum-sensing and anti-phagocytic activity were also identified. Potential plasmids with replicon sequences (rep1, rep2, repUS43, repUS47, rep9a, rep9b) and other mobile genetic elements (Tn917, cn_5536_ISEnfa1, Tn6009, ISEnfa1, ISEfa10) were detected. Clinically relevant E. faecium ST32 and ST416 clones were identified in meat samples.

Conclusion

The occurrence of antimicrobial-resistant Enterococcus spp. in livestock and raw meat samples, carrying multiple resistance and virulence genes, including known clones associated with hospital-acquired infections, underscores the critical need for employing robust tools like whole genome sequencing. Such tools provide detailed data essential for ongoing surveillance efforts aimed at addressing the challenge of antimicrobial resistance with a focus on one health.
Available and novel plant-based carbon dots derived from Vaccaria Semen carbonisata alleviates liver fibrosis
Authors: Zhao Yafang , Dai Ertong , Dong Liyang , Yuan Jinye , Zhao Yusheng , Wu Tong , Kong Ruolan , Li Menghan , Wang Shuxian , Zhou Long , Yang Yingxin , Kong Hui , Zhao Yan , Qu Huihua
Published: December 2023

Background: Liver fibrosis represents an intermediate stage in the progression of liver disease, and as of now, there exists no established clinical therapy for effective antifibrotic treatment.

Purpose: Our aim is to explore the impact of Carbon dots derived from Vaccaria Semen Carbonisata (VSC-CDs) on carbon tetrachloride-induced liver fibrosis in mice.

Methods: VSC-CDs were synthesized employing a modified pyrolysis process. Comprehensive characterization was performed utilizing various techniques, including transmission electron microscopy (TEM), multiple spectroscopies, X-ray photoelectron spectroscopy (XPS), and high-performance liquid chromatography (HPLC). A hepatic fibrosis model induced by carbon tetrachloride was utilized to evaluate the anti-hepatic fibrosis effects of VSC-CDs.

Results: VSC-CDs, exhibiting a quantum yield (QY) of approximately 2.08%, were nearly spherical with diameters ranging from 1.0 to 5.5 nm. The VSC-CDs prepared in this study featured a negative charge and abundant chemical functional groups. Furthermore, these particles demonstrated outstanding dispersibility in the aqueous phase and high biocompatibility. Moreover, VSC-CDs not only enhanced liver function and alleviated liver damage in pathomorphology but also mitigated the extent of liver fibrosis. Additionally, this study marks the inaugural demonstration of the pronounced activity of VSC-CDs in inhibiting inflammatory reactions, reducing oxidative damage, and modulating the TGF-β/Smad signaling pathway.

Conclusion: VSC-CDs exerted significant potential for application in nanodrugs aimed at treating liver fibrosis.
Altered dynamical integration/segregation balance during anesthesia-induced loss of consciousness
Authors: Lord Louis-David , Carletti Timoteo , Fernandes Henrique , Turkheimer Federico E. , Expert Paul
Published: December 2023

In recent years, brain imaging studies have begun to shed light on the neural correlates of physiologically-reversible altered states of consciousness such as deep sleep, anesthesia, and psychedelic experiences. The emerging consensus is that normal waking consciousness requires the exploration of a dynamical repertoire enabling both global integration i.e., long-distance interactions between brain regions, and segregation, i.e., local processing in functionally specialized clusters. Altered states of consciousness have notably been characterized by a tipping of the integration/segregation balance away from this equilibrium. Historically, functional MRI (fMRI) has been the modality of choice for such investigations. However, fMRI does not enable characterization of the integration/segregation balance at sub-second temporal resolution. Here, we investigated global brain spatiotemporal patterns in electrocorticography (ECoG) data of a monkey (Macaca fuscata) under either ketamine or propofol general anesthesia. We first studied the effects of these anesthetics from the perspective of band-specific synchronization across the entire ECoG array, treating individual channels as oscillators. We further aimed to determine whether synchrony within spatially localized clusters of oscillators was differently affected by the drugs in comparison to synchronization over spatially distributed subsets of ECoG channels, thereby quantifying changes in integration/segregation balance on physiologically-relevant time scales. The findings reflect global brain dynamics characterized by a loss of long-range integration in multiple frequency bands under both ketamine and propofol anesthesia, most pronounced in the beta (13–30 Hz) and low-gamma bands (30–80 Hz), and with strongly preserved local synchrony in all bands.
Quality appraisal of clinical practice guidelines for the management of Dysphagia after acute stroke
Authors: Gao Shi-Lin , Liu Chang-Qing , Han Qing-Hua , Dai Xiao-Rong , Liu Yi-Wen , Li Ka
Published: December 2023

Objectives

Dysphagia is a common complication in stroke patients, widely affecting recovery and quality of life after stroke. The objective of this systematic review is to identify the gaps that between evidence and practice by critically assessing the quality of clinical practice guidelines (CPGs) for management of dysphagia in stroke.

Methods

We systematically searched academic databases and guideline repositories between January 1, 2014, and August 1, 2023. The Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument was used by two authors to independently assess CPG quality.

Results

In a total of 14 CPGs included, we identified that three CPGs obtained a final evaluation of “high quality,” nine CPGs achieved “moderate quality” and two CPGs received “low quality.” The domain of “scope and purpose” achieved the highest mean score (91.1%) and the highest median (IQR) of 91.7% (86.1, 94.4%), while the domain of “applicability” received the lowest mean score (55.8%) and the lowest median (IQR) of 55.4% (43.2, 75.5%).

Conclusion

The CPG development group should pay more attention to improving the methodological quality according to the AGREE II instrument, especially in the domain of “applicability” and “stakeholder involvement;” and each item should be refined as much as possible.
MMGan: a multimodal MR brain tumor image segmentation method
Authors: Gao Leiyi , Li Jiao , Zhang Ruixin , Bekele Hailu Hanna , Wang Junzhu , Cheng Yining , Deng Hongxia
Published: December 2023

Computer-aided diagnosis has emerged as a rapidly evolving field, garnering increased attention in recent years. At the forefront of this field is the segmentation of lesions in medical images, which is a critical preliminary stage in subsequent treatment procedures. Among the most challenging tasks in medical image analysis is the accurate and automated segmentation of brain tumors in various modalities of brain tumor MRI. In this article, we present a novel end-to-end network architecture called MMGan, which combines the advantages of residual learning and generative adversarial neural networks inspired by classical generative adversarial networks. The segmenter in the MMGan network, which has a U-Net architecture, is constructed using a deep residual network instead of the conventional convolutional neural network. The dataset used for this study is the BRATS dataset from the Brain Tumor Segmentation Challenge at the Medical Image Computing and Computer Assisted Intervention Society. Our proposed method has been extensively tested, and the results indicate that this MMGan framework is more efficient and stable for segmentation tasks. On BRATS 2019, the segmentation algorithm improved accuracy and sensitivity in whole tumor, tumor core, and enhanced tumor segmentation. Particularly noteworthy is the higher dice score of 0.86 achieved by our proposed method in tumor core segmentation, surpassing those of stateof-the-art models. This study improves the accuracy and sensitivity of the tumor segmentation task, which we believe is significant for medical image analysis. And it should be further improved by replacing different loss functions such as cross-entropy loss function and other methods.
The neural circuits and molecular mechanisms underlying fear dysregulation in posttraumatic stress disorder
Authors: Iqbal Javed , Huang Geng-Di , Xue Yan-Xue , Yang Mei , Jia Xiao-Jian
Published: December 2023

Post-traumatic stress disorder (PTSD) is a stress-associated complex and debilitating psychiatric disorder due to an imbalance of neurotransmitters in response to traumatic events or fear. PTSD is characterized by re-experiencing, avoidance behavior, hyperarousal, negative emotions, insomnia, personality changes, and memory problems following exposure to severe trauma. However, the biological mechanisms and symptomatology underlying this disorder are still largely unknown or poorly understood. Considerable evidence shows that PTSD results from a dysfunction in highly conserved brain systems involved in regulating stress, anxiety, fear, and reward circuitry. This review provides a contemporary update about PTSD, including new data from the clinical and preclinical literature on stress, PTSD, and fear memory consolidation and extinction processes. First, we present an overview of well-established laboratory models of PTSD and discuss their clinical translational value for finding various treatments for PTSD. We then highlight the research progress on the neural circuits of fear and extinction-related behavior, including the prefrontal cortex, hippocampus, and amygdala. We further describe different molecular mechanisms, including GABAergic, glutamatergic, cholinergic, and neurotropic signaling, responsible for the structural and functional changes during fear acquisition and fear extinction processes in PTSD.
Explainable stress type classification captures physiologically relevant responses in the Maastricht Acute Stress Test
Authors: Tervonen Jaakko , Närväinen Johanna , Mäntyjärvi Jani , Pettersson Kati
Published: December 2023

Introduction

Current stress detection methods concentrate on identification of stress and non-stress states despite the existence of various stress types. The present study performs a more specific, explainable stress classification, which could provide valuable information on the physiological stress reactions.

Methods

Physiological responses were measured in the Maastricht Acute Stress Test (MAST), comprising alternating trials of cold pressor (inducing physiological stress and pain) and mental arithmetics (eliciting cognitive and social-evaluative stress). The responses in these subtasks were compared to each other and to the baseline through mixed model analysis. Subsequently, stress type detection was conducted with a comprehensive analysis of several machine learning components affecting classification. Finally, explainable artificial intelligence (XAI) methods were applied to analyze the influence of physiological features on model behavior.

Results

Most of the investigated physiological reactions were specific to the stressors, and the subtasks could be distinguished from baseline with up to 86.5% balanced accuracy. The choice of the physiological signals to measure (up to 25%-point difference in balanced accuracy) and the selection of features (up to 7%-point difference) were the two key components in classification. Reflection of the XAI analysis to mixed model results and human physiology revealed that the stress detection model concentrated on physiological features relevant for the two stressors.

Discussion

The findings confirm that multimodal machine learning classification can detect different types of stress reactions from baseline while focusing on physiologically sensible changes. Since the measured signals and feature selection affected classification performance the most, data analytic choices left limited input information uncompensated.
CAR-T treatment for cancer: prospects and challenges
Authors: Chen Ran , Chen Lei , Wang Chaoqun , Zhu Hua , Gu Lijuan , Li Yuntao , Xiong Xiaoxing , Chen Gang , Jian Zhihong
Published: December 2023

Chimeric antigen receptor (CAR-T) cell therapy has been widely used in hematological malignancies and has achieved remarkable results, but its long-term efficacy in solid tumors is greatly limited by factors such as the tumor microenvironment (TME). In this paper, we discuss the latest research and future views on CAR-T cell cancer immunotherapy, compare the different characteristics of traditional immunotherapy and CAR-T cell therapy, introduce the latest progress in CAR-T cell immunotherapy, and analyze the obstacles that hinder the efficacy of CAR-T cell therapy, including immunosuppressive factors, metabolic energy deficiency, and physical barriers. We then further discuss the latest therapeutic strategies to overcome these barriers, as well as management decisions regarding the possible safety issues of CAR-T cell therapy, to facilitate solutions to the limited use of CAR-T immunotherapy.
KRAS-related miR-143 expression is associated with lymph node involvement and correlates with outcome in pancreatic adenocarcinoma patients
Authors: Lavacchi Daniele , Polvani Simone , Taddei Antonio , Scolari Federico , Messerini Luca , Caliman Enrico , Moraldi Luca , Guidolin Alessia , Grazi Gian Luca , Galli Andrea , Pillozzi Serena , Antonuzzo Lorenzo
Published: December 2023

Introduction

Pancreatic adenocarcinoma (PC) is one of the most lethal malignancies; even after resection the patients’ 5-year disease-free survival (DFS) is lower than 26%. The genetic mutational landscape of PC is dominated by activating KRAS mutations, that have been reported in approximately 90% of cases; however, beyond KRAS - direct mutations, several KRAS-targeting miRNAs appear to be downregulated, strengthening the already activated RAS signaling. In addition, the interplay between miRNAs and RAS includes poorly investigated downstream miRNAs. The aim of this study was to determine the prognostic value of some of these candidate KRAS-related miRNAs.

Patients and methods

Between 2015 and 2022, 44 patients with pathologically confirmed PC, who received surgery and were enrolled by the Clinical Oncology Unit, Careggi University Hospital, Florence (Italy). PC Total RNA was extracted from FFPE sections, retro-transcribed and the resulting cDNA was then used for qPCR analysis. A panel of KRAS-related miRNA (miR-155, miR-206 and miR-143) was analyzed.

Results

In this observational study patients sex distribution was unequal with 34.1% being male and 65.9% female. The most frequent tumor localization was the head of the pancreas (65.9%) and the pathological stages were pT1-2 (45.5%), pT3 (54.5%), pN0 (22.7%), pN+ (77.3%). Adjuvant therapy was administered to 63.6% of patients; disease recurrence was observed in 69% of cases. Twenty-three patients, whose RNA was of adequate quality, were used in the mRNAs expression studies. When comparing the miRNA expression between PC and a pool of healthy tissues, miR-155 was overexpressed and miR-206 downregulated in PC, while miR-143 expression was unchanged. However, when categorized in low- and high- miR-143 expressing PC (according to the median value), high miR-143 was associated with nodal involvement (pN+) (p=0.029), who in turn was linked with shorter DFS (p=0.009) and overall survival (OS) (p=0.021) compared to pN0. A trend toward inferior DFS was observed for higher expression of miR-206 (p=0.095) and miR-143 (p=0.092). Finally, responders to a first-line treatment for advanced disease had miR-155 overexpressed (p=0.048).

Conclusions

miRNAs are involved in PC tumorigenesis and metastatic spread. In light of miR-143 association with lymphatic spread and poor prognosis, a comprehensive analysis of miRNA interplay with KRAS deserves further investigation.
Complementary authentication of Chinese herbal products to treat endometriosis using DNA metabarcoding and HPTLC shows a high level of variability
Authors: Mück Felicitas , Scotti Francesca , Mauvisseau Quentin , Raclariu-Manolică Ancuţa Cristina , Schrøder-Nielsen Audun , Wangensteen Helle , de Boer Hugo J.
Published: December 2023

Traditional Chinese Medicine (TCM) is popular for the treatment of endometriosis, a complex gynecological disease that affects 10% of women globally. The growing market for TCMs has yielded a significant incentive for product adulteration, and although emerging technologies show promise to improve their quality control, many challenges remain. We tested the authenticity of two traditional Chinese herbal formulae used in women’s healthcare for the treatment of endometriosis, known as Gui Zhi Fu Ling Wan (FL) and Ge Xia Zhu Yu Tang (GX). Dual-locus DNA metabarcoding analysis coupled with high-performance thin-layer chromatography (HPTLC) were used to authenticate 19 FL and six GX commercial herbal products, as well as three ad hoc prepared artificial mixtures. HPTLC was able to detect most of the expected ingredients via comparative component analysis. DNA metabarcoding was able to detect an unexpected species diversity in the products, including 38 unexpected taxa. Chromatography has a resolution for all species indirectly through the identification of marker compounds for the different species ingredients. Metabarcoding on the other hand yields an overview of species diversity in each sample, but interpretation of the results can be challenging. Detected species might not be present in quantities that matter, and without validated quantification, some detected species can be hard to interpret. Comparative analysis of the two analytical approaches also reveals that DNA for species might be absent or too fragmented to amplify as the relevant chemical marker compounds can be detected but no amplicons are assigned to the same species. Our study emphasizes that integrating DNA metabarcoding with phytochemical analysis brings valuable data for the comprehensive authentication of Traditional Chinese Medicines ensuring their quality and safe use.
Establishment of a multicomponent quality control method and the transfer characteristics of five markers from Qidongning Formula to rat tissues by HPLC-QQQ-MS/MS
Authors: Zhou Di , Chen Jian-Ru , Yang Zi-Qi , Xu Ling , Huang Yu-Feng
Published: December 2023

Introduction: Traditional Chinese medicine compound preparations have become an increasingly utilized strategy for tumour treatment. Qidongning Formula (QDN) is a kind of antitumour compound preparation used in hospitals, and it can inhibit the growth of lung cancer cells. However, due to the complexity of botanical drugs, the quality evaluation of QDN is inconsistent, affecting clinical efficacy and posing potential safety risks for clinical application. Additionally, tissue distribution is an integral part of the drug development process.

Methods: To study the distribution characteristics of markers in compound preparations and rat tissues, a novel HPLC-QQQ-MS/MS quantitative analytical method was established to determine five markers in QDN simultaneously, and the method was verified.

Results and discussion: The analytical results showed that the contents of salidroside (51.6 ± 5.75 μg/g), calycosin-7-O-β-D-glucoside (94.2 ± 15.4 μg/g), specnuezhenide (371 ± 72.5 μg/g), formononetin (23.8 ± 5.39 μg/g), and polyphyllin I (87.7 ± 10.6 μg/g) were stable in different batches of QDN. After intragastric administration (13.5 g/kg) in rats for 1 h, four markers in the QDN, except polyphyllin I, were distributed in most tissues. QDN was distributed chiefly in the stomach and small intestine, followed by the liver or kidney. The study also found that specnuezhenide had the highest concentration in both QDN and rat tissues (102 ± 22.1 μg/g in the stomach), while formononetin had the highest transfer rate (0.351%) from QDN to rat intestines. The above research lays a quality research foundation for the antitumour application of QDN and provides a scientific reference for the quality control of Chinese medicine compound preparations.
Methods for assessing cardiac myofilament calcium sensitivity
Authors: Dowrick Jarrah M. , Taberner Andrew J. , Han June-Chiew , Tran Kenneth
Published: December 2023

Myofilament calcium (Ca2+) sensitivity is one of several mechanisms by which force production of cardiac muscle is modulated to meet the ever-changing demands placed on the heart. Compromised Ca2+ sensitivity is associated with pathologies, which makes it a parameter of interest for researchers. Ca2+ Sensitivity is the ratio of the association and dissociation rates between troponin C (TnC) and Ca2+. As it is not currently possible to measure these rates in tissue preparations directly, methods have been developed to infer myofilament sensitivity, typically using some combination of force and Ca2+ measurements. The current gold-standard approach constructs a steady-state force-Ca2+ relation by exposing permeabilised muscle samples to a range of Ca2+ concentrations and uses the half-maximal concentration as a proxy for sensitivity. While a valuable method for steady-state investigations, the permeabilisation process makes the method unsuitable when examining dynamic, i.e., twitch-to-twitch, changes in myofilament sensitivity. The ability of the heart to transiently adapt to changes in load is an important consideration when evaluating the impact of disease states. Alternative methods have been proffered, including force-Ca2+ phase loops, potassium contracture, hybrid experimental-modelling and conformation-based fluorophore approaches. This review provides an overview of the mechanisms underlying myofilament Ca2+ sensitivity, summarises existing methods, and explores, with modelling, whether any of them are suited to investigating dynamic changes in sensitivity. We conclude that a method that equips researchers to investigate the transient change of myofilament Ca2+ sensitivity is still needed. We propose that such a method will involve simultaneous measurements of cytosolic Ca2+ and TnC activation in actively twitching muscle and a biophysical model to interpret these data.
Stability in the leaf functional traits of understory herbaceous species after 12-yr of nitrogen addition in temperate larch plantations
Authors: Yan Tao , Wang Liying , Wang Peilin , Zhong Tianyu
Published: December 2023

Leaf functional traits play critical roles in plant functioning. Although the functional traits of overstory trees have been extensively studied, minimal research has been conducted regarding understory species, despite the understory layer is an important component of temperate forests. Such insufficiency limit the broader understanding of processes and functions in forest ecosystems, particularly when under the increasing atmospheric nitrogen (N) deposition. Here, we investigated the responses of 18 leaf functional traits in six understory herbaceous species within young and mature stands (three species per stand) in larch (Larix principis-rupprechtii) plantations that subjected to 12 years of anthropogenic N addition. We found that N addition did not significantly impact the photosynthetic traits of understory herbaceous species in either stand; it only led to increased chlorophyll content in Geum aleppicum Jacq. Similarly, with the exception of decreases in the predawn leaf water potential of Sanguisorba officinalis L., N addition did not significantly affect leaf hydraulic traits. With the exception of changes to adaxial epidermis thickness in Potentilla chinensis Ser. (decreased) and G. aleppicum (increased), N addition had negligible effects on leaf anatomical traits and specific leaf area, however, interspecific variations in the plasticity of leaf anatomical traits were observed. Stable responses to N addition were also observed for nonstructural carbohydrates (NSC) and their components (soluble sugars and starch), with the exception of Polygonum divaricatum L., which exhibited increases in NSC. Overall, our results suggest that the functional traits of understory herbaceous species exhibit stability under conditions of long-term N enrichment in temperate plantations.
Genome-wide identification and expression analysis of the KCS gene family in soybean (Glycine max) reveal their potential roles in response to abiotic stress
Authors: Gong Yujie , Wang Deying , Xie Haojie , Zhao Zewei , Chen Yuyue , Zhang Dongxue , Jiao Yexuan , Shi Mengmeng , Lv Peng , Sha Qi , Yang Jing , Chu Pengfei , Sun Yongwang
Published: December 2023

Very long chain fatty acids (VLCFAs) are fatty acids with chain lengths of 20 or more carbon atoms, which are the building blocks of various lipids that regulate developmental processes and plant stress responses. 3-ketoacyl-CoA synthase encoded by the KCS gene is the key rate-limiting enzyme in VLCFA biosynthesis, but the KCS gene family in soybean (Glycine max) has not been adequately studied thus far. In this study, 31 KCS genes (namely GmKCS1 - GmKCS31) were identified in the soybean genome, which are unevenly distributed on 14 chromosomes. These GmKCS genes could be phylogenetically classified into seven groups. A total of 27 paralogous GmKCS gene pairs were identified with their Ka/Ks ratios indicating that they had undergone purifying selection during soybean genome expansion. Cis-acting element analysis revealed that GmKCS promoters contained multiple hormone- and stress-responsive elements, indicating that GmKCS gene expression levels may be regulated by various developmental and environmental stimuli. Expression profiles derived from RNA-seq data and qRT-PCR experiments indicated that GmKCS genes were diversely expressed in different organs/tissues, and many GmKCS genes were found to be differentially expressed in the leaves under cold, heat, salt, and drought stresses, suggesting their critical role in soybean resistance to abiotic stress. These results provide fundamental information about the soybean KCS genes and will aid in their further functional elucidation and exploitation.
Unmet expectations: social inclusion and the interaction between social anxiety and ambiguous or positive feedback
Authors: Thériault Rémi , Dion-Cliche Flavie , Dandeneau Stéphane
Published: December 2023

Introduction

This study explores the impact of preferential inclusion on fulfilling basic needs following ambiguous or positive social feedback, considering the moderating effect of social anxiety.

Methods

Participants (N = 438) received either positive or ambiguous social feedback and engaged in a social participation or preferential social inclusion task. They completed measures of the fulfillment of their fundamental needs, social anxiety, and other personality traits.

Results

The results indicate that preferential social inclusion (Uberball condition) enhances the fulfillment of fundamental needs compared to social participation (Cyberball inclusion condition). Furthermore, receiving positive social feedback considerably strengthens the negative relationship between social anxiety and fundamental need fulfillment when followed by ordinary social participation relative to preferential social inclusion presumably because these individuals react more strongly to unmet expectations of extreme social acceptance.

Discussion

This research suggests that individuals with high social anxiety may not experience the usual benefits of social participation unless they experience extreme social inclusion.
Spatiotemporal characteristic analysis of PM2.5 in central China and modeling of driving factors based on MGWR: a case study of Henan Province
Authors: Wang Hua , Zhang Mingcheng , Niu Jiqiang , Zheng Xiaoyun
Published: December 2023

Since the start of the twenty-first century, China's economy has grown at a high or moderate rate, and air pollution has become increasingly severe. The study was conducted using data from remote sensing observations between 1998 and 2019, employing the standard deviation ellipse model and spatial autocorrelation analysis, to explore the spatiotemporal distribution characteristics of PM2.5 in Henan Province. Additionally, a multiscale geographically weighted regression model (MGWR) was applied to explore the impact of 12 driving factors (e.g., mean surface temperature and CO2 emissions) on PM2.5 concentration. The research revealed that (1) Over a period of 22 years, the yearly mean PM2.5 concentrations in Henan Province demonstrated a trend resembling the shape of the letter “M”, and the general trend observed in Henan Province demonstrated that the spatial center of gravity of PM2.5 concentrations shifted toward the north. (2) Distinct spatial clustering patterns of PM2.5 were observed in Henan Province, with the northern region showing a primary concentration of spatial hot spots, while the western and southern areas were predominantly characterized as cold spots. (3) MGWR is more effective than GWR in unveiling the spatial heterogeneity of influencing factors at various scales, thereby making it a more appropriate approach for investigating the driving mechanisms behind PM2.5 concentration. (4) The results acquired from the MGWR model indicate that there are varying degrees of spatial heterogeneity in the effects of various factors on PM2.5 concentration. To summarize the above conclusions, the management of the atmospheric environment in Henan Province still has a long way to go, and the formulation of relevant policies should be adapted to local conditions, taking into account the spatial scale effect of the impact of different influencing factors on PM2.5.