bluuebunny/crossref_metadata_2025 huggingface dataset:
Astrogliosis in multiple sclerosis and neuro-inflammation: what role for the notch pathway?
Authors: Mora Pierre , Chapouly Candice
Published: October 2023

Multiple sclerosis is an autoimmune inflammatory disease of the central nervous system leading to neurodegeneration. It affects 2.3 million people worldwide, generally younger than 50. There is no known cure for the disease, and current treatment options - mainly immunotherapies to limit disease progression - are few and associated with serious side effects. In multiple sclerosis, disruption of the blood-brain barrier is an early event in the pathogenesis of lesions, predisposing to edema, excito-toxicity and inflammatory infiltration into the central nervous system. Recently, the vision of the blood brain barrier structure and integrity has changed and include contributions from all components of the neurovascular unit, among which astrocytes. During neuro-inflammation, astrocytes become reactive. They undergo morphological and molecular changes named “astrogliosis” driving the conversion from acute inflammatory injury to a chronic neurodegenerative state. Astrogliosis mechanisms are minimally explored despite their significance in regulating the autoimmune response during multiple sclerosis. Therefore, in this review, we take stock of the state of knowledge regarding astrogliosis in neuro-inflammation and highlight the central role of NOTCH signaling in the process of astrocyte reactivity. Indeed, a very detailed nomenclature published in nature neurosciences in 2021, listing all the reactive astrocyte markers fully identified in the literature, doesn’t cover the NOTCH signaling. Hence, we discuss evidence supporting NOTCH1 receptor as a central regulator of astrogliosis in the pathophysiology of neuro-inflammation, notably multiple sclerosis, in human and experimental models.
Circulating miRNA expression in extracellular vesicles is associated with specific injuries after multiple trauma and surgical invasiveness
Authors: Groven Rald Victor Maria , Greven Johannes , Mert Ümit , Horst Klemens , Zhao Qun , Blokhuis Taco Johan , Huber-Lang Markus , Hildebrand Frank , van Griensven Martijn
Published: October 2023

Introduction

Two trauma treatment principles are Early Total Care (ETC), and Damage Control Orthopedics (DCO). Cellular mechanisms that underlie the connection between treatment type, its systemic effects, and tissue regeneration are not fully known. Therefore, this study aimed to: 1) profile microRNA (miRNA) expression in plasma derived Extracellular Vesicles (EVs) from a porcine multiple trauma model at different timepoints, comparing two surgical treatments; and 2) determine and validate the miRNA’s messengerRNA (mRNA) targets.

Methods

The porcine multiple trauma model consisted of blunt chest trauma, liver laceration, bilateral femur fractures, and controlled haemorrhagic shock. Two treatment groups were defined, ETC (n=8), and DCO (n=8). Animals were monitored under Intensive Care Unit-standards, blood was sampled at 1.5, 2.5, 24, and 72 hours after trauma, and EVs were harvested from plasma. MiRNAs were analysed using quantitative Polymerase Chain Reaction arrays. MRNA targets were identified in silico and validated in vivo in lung and liver tissue.

Results

The arrays showed distinct treatment specific miRNA expression patterns throughout all timepoints, and miRNAs related to the multiple trauma and its individual injuries. EV-packed miRNA expression in the ETC group was more pro-inflammatory, indicating potentially decreased tissue regenerative capacities in the acute post-traumatic phase. In silico target prediction revealed several overlapping mRNA targets among the identified miRNAs, related to inflammation, (pulmonary) fibrosis, and Wnt-signalling. These were, among others, A Disintegrin and Metalloproteinase domain-containing protein 10, Collagen Type 1 Alpha 1 Chain, Catenin Beta Interacting Protein 1, and Signal Transducers and Activators of Transcription 3. Validation of these mRNA targets in the lung showed significant, treatment specific deregulations which matched the expression of their upstream miRNAs. No significant mRNA deregulations were observed in the liver.

Discussion

This study showed treatment specific, EV-packed miRNA expression patterns after trauma that correlated with mRNA expressions in the lungs, target organs over distance. A systemic response to the increased surgical trauma in the ETC group was identified, with various miRNAs associated with injuries from the trauma model, and involved in (systemic) inflammation, tissue regeneration. EV-transported miRNAs demonstrated a clear role in multiple trauma, warranting further research into tissue-tissue talk and therapeutic applications of EVs after trauma.
The role of amino acid metabolism in inflammatory bowel disease and other inflammatory diseases
Authors: Zheng Xiaowen , Zhu Yi , Zhao Zihan , Chu Ying , Yang Wenjing
Published: October 2023

Inflammation is a characteristic symptom of the occurrence and development of many diseases, which is mainly characterized by the infiltration of inflammatory cells such as macrophages and granulocytes, and the increased release of proinflammatory factors. Subsequently, macrophage differentiates and T cells and other regulated factors exhibit anti-inflammatory function, releasing pro- and anti-inflammatory factors to maintain homeostasis. Although reports define various degrees of metabolic disorders in both the inflamed and non-inflamed parts of inflammatory diseases, little is known about the changes in amino acid metabolism in such conditions. This review aims to summarize amino acid changes and mechanisms involved in the progression of inflammatory bowel disease (IBD) and other inflammatory diseases. Since mesenchymal stem cells (MSCs) and their derived exosomes (MSC-EXO) have been found to show promising effects in the treatment of IBD and other inflammatory diseases,their potential in the modulation of amino acid metabolism in the treatment of inflammation is also discussed.
The synergistic effects of polyphenols and intestinal microbiota on osteoporosis
Authors: Wang Keyu , Hu Siwang
Published: October 2023

Osteoporosis is a common metabolic disease in middle-aged and elderly people. It is characterized by a reduction in bone mass, compromised bone microstructure, heightened bone fragility, and an increased susceptibility to fractures. The dynamic imbalance between osteoblast and osteoclast populations is a decisive factor in the occurrence of osteoporosis. With the increase in the elderly population in society, the incidence of osteoporosis, disability, and mortality have gradually increased. Polyphenols are a fascinating class of compounds that are found in both food and medicine and exhibit a variety of biological activities with significant health benefits. As a component of food, polyphenols not only provide color, flavor, and aroma but also act as potent antioxidants, protecting our cells from oxidative stress and reducing the risk of chronic disease. Moreover, these natural compounds exhibit anti-inflammatory properties, which aid in immune response regulation and potentially alleviate symptoms of diverse ailments. The gut microbiota can degrade polyphenols into more absorbable metabolites, thereby increasing their bioavailability. Polyphenols can also shape the gut microbiota and increase its abundance. Therefore, studying the synergistic effect between gut microbiota and polyphenols may help in the treatment and prevention of osteoporosis. By delving into how gut microbiota can enhance the bioavailability of polyphenols and how polyphenols can shape the gut microbiota and increase its abundance, this review offers valuable information and references for the treatment and prevention of osteoporosis.
Intestinal factors promoting the development of RORγt+ cells and oral tolerance
Authors: López-Fandiño Rosina , Molina Elena , Lozano-Ojalvo Daniel
Published: October 2023

The gastrointestinal tract has to harmonize the two seemingly opposite functions of fulfilling nutritional needs and avoiding the entry of pathogens, toxins and agents that can cause physical damage. This balance requires a constant adjustment of absorptive and defending functions by sensing environmental changes or noxious substances and initiating adaptive or protective mechanisms against them through a complex network of receptors integrated with the central nervous system that communicate with cells of the innate and adaptive immune system. Effective homeostatic processes at barrier sites take the responsibility for oral tolerance, which protects from adverse reactions to food that cause allergic diseases. During a very specific time interval in early life, the establishment of a stable microbiota in the large intestine is sufficient to prevent pathological events in adulthood towards a much larger bacterial community and provide tolerance towards diverse food antigens encountered later in life. The beneficial effects of the microbiome are mainly exerted by innate and adaptive cells that express the transcription factor RORγt, in whose generation, mediated by different bacterial metabolites, retinoic acid signalling plays a predominant role. In addition, recent investigations indicate that food antigens also contribute, analogously to microbial-derived signals, to educating innate immune cells and instructing the development and function of RORγt+ cells in the small intestine, complementing and expanding the tolerogenic effect of the microbiome in the colon. This review addresses the mechanisms through which microbiota-produced metabolites and dietary antigens maintain intestinal homeostasis, highlighting the complementarity and redundancy between their functions.
Crosstalk between gut microbiota and metastasis in colorectal cancer: implication of neutrophil extracellular traps
Authors: Wu Jiawei , Dong Wenyan , Pan Yayun , Wang Jingjing , Wu Minliang , Yu Yue
Published: October 2023

Primary colorectal cancer (CRC) often leads to liver metastasis, possibly due to the formation of pre-metastatic niche (PMN) in liver. Thus, unravelling the key modulator in metastasis is important for the development of clinical therapies. Gut microbiota dysregulation is a key event during CRC progression and metastasis. Numerous studies have elucidated the correlation between specific gut bacteria strains (e.g., pks+E. coli and Bacteroides fragilis) and CRC initiation, and gut bacteria translocation is commonly witnessed during CRC progression. Gut microbiota shapes tumor microenvironment (TME) through direct contact with immune cells or through its functional metabolites. However, how gut microbiota facilitates CRC metastasis remains controversial. Meanwhile, recent studies identify the dissemination of bacteria from gut lumen to liver, suggesting the role of gut microbiota in shaping tumor PMN. A pro-tumoral PMN is characterized by the infiltration of immunosuppressive cells and increased pro-inflammatory immune responses. Notably, neutrophils form web-like structures known as neutrophil extracellular traps (NETs) both in primary TME and metastatic sites, NETs are involved in cancer progression and metastasis. In this review, we focus on the role of gut microbiota in CRC progression and metastasis, highlight the multiple functions of different immune cell types in TME, especially neutrophils and NETs, discuss the possible mechanisms of gut microbiota in shaping PMN formation, and provide therapeutical indications in clinic.
Marine distribution and habitat use by Snow Petrels Pagodroma nivea in East Antarctica throughout the non-breeding period
Authors: Viola Benjamin , Wienecke Barbara , Green Cara-Paige , Corney Stuart , Raymond Ben , Southwell Colin , Sumner Michael D. , Virtue Patti , Wotherspoon Simon , Emmerson Louise
Published: October 2023

The relationships between flying Antarctic seabirds and their at-sea environments remain poorly understood, particularly outside of the breeding season. Improving our knowledge of how these marine predators use their habitat is a critical step towards conservation of these species. We tracked 27 adult Snow Petrels from two large breeding colonies in East Antarctica during the Austral winter (non-breeding period) – when they are primarily at sea away from their nesting sites. During this time, Snow Petrel habitat use was most associated with bathymetry (> 5000 m), low sea-surface height, relatively close distance to the southern boundary of the Antarctic Circumpolar Current, relatively close distance to the ice-edge, relatively high sea-ice concentration, and low sea-surface temperature. Individuals displayed various movement patterns: 20 birds occupied overlapping winter areas that ranged broadly (up to 2000 km) from their breeding sites. The remaining birds ventured far beyond their breeding sites – reaching a maximal distance from the colony of 5,268 km. One individual circumnavigated Antarctica. Daily activity patterns were related to day length, with peak activity occurring near dawn and dusk. Nocturnal activity increased from March until August/September. Key results reveal and depict Snow Petrel habitat maps for the non-breeding period in the East Antarctic region.
Evaluation of the impact of reliance on the regulatory performance in the South African Health Products Regulatory Authority: implications for African regulatory authorities
Authors: Danks Lorraine , Semete-Makokotlela Boitumelo , Otwombe Kennedy , Parag Yashmika , Walker Stuart , Salek Sam
Published: October 2023

Introduction

The World Health Organization (WHO) advocates the use of reliance practices to enable national regulatory authorities (NRAs) to improve patients’ access to medicines. This study considered whether reliance review translates into swifter medicine authorization.

Methods

Abridged review outcomes were examined for New Chemical Entity (NCE) and generic applications to the South African Health Products Regulatory Authority (SAHPRA) in Chemistry, Manufacturing and Controls (CMC) and clinical/bioequivalence (BE), as well as overall NCE authorization times.

Results

SAHPRA NCE CMC review time was 91 days (abridged) vs. 179 days (full), applicant response time was 34 vs. 105 days, respectively, and there was a >2-fold time reduction for abridged vs. full CMC review (125 vs. 284 days). There was a 99-day decrease in clinical approval time through an abridged review (230 vs. 329 days) and a decrease in marketing authorization time for NCE abridged assessment (446 vs. 619 days). SAHPRA review time for generic applications was 97 days (abridged) vs. 191 days (full); applicant response time was 26 days (abridged) vs. 81 days (full) and there was a >2-fold time reduction for CMC and BE abridged vs. full review (122 vs. 272 days).

Conclusion

These results clearly support World Health Organization recommendations for the use of reliance-based regulatory review to expedite the worldwide availability of safe, effective and needed medications.
Soil microbial diversity under different types of interference in birch secondary forest in the Greater Khingan Mountains in China
Authors: Zhai Kaitao , Hua Yongchun , Liang Jingwen , Li Jing , Wang Zirui , Liu Lei , Gao Minglong , Sa Rula , Zhao Mingmin
Published: October 2023

Introduction

Soil microorganisms are an important component of soil ecosystems with an indispensable role in forest ecosystems. We analyzed the soil microbial diversity in birch secondary forest formed by natural restoration or artificial reconstruction after interference by burning, clear cutting, and gradient cutting, and the Betula platyphylla Suk undisturbed forest in the Greater Khingan Mountains in China.

Methods

Illumina high-throughput sequencing technology was used to analyze the characteristics of the soil microbial community during the restoration process of birch secondary forest caused by the different types of interference. The relationships between bacteria and fungi were analyzed. The gene functions of the soil bacterial community and the ecological functions of soil fungi were predicted using PICRUSt and FunGuild, respectively.

Results

At the phylum level, the species and quantity of bacteria were more abundant than that of fungi. At the genus level, no obvious differences in the abundance of bacteria were observed; there were obvious differences in the abundance of fungi. Among the eight sample plots, the artificial larch forest belt had the highest bacterial and fungal alpha diversity, which was slightly higher than undisturbed forest, while the other sample plots were significantly lower. Gradual cutting pure birch forest bacteria and fungi had the highest beta diversity, and artificial larch forest belt bacteria and heavy burn sample plot fungi had the lowest beta diversity. Samples from the cutting and burning sample plots were significantly different from the undisturbed forest at the phylum level of Acidobacteriae, Acidimicrobiia, Mortierellomycetes and Sordariomycetes. We found statistical differences in biomarkers between bacterial and fungal communities in undisturbed forest and artificial larch forest belt and burn sample plots. PICRUSt prediction and FunGuild prediction showed that soil bacterial and fungal communities were rich in gene and ecological functions, respectively. In the microbial network, the stability or anti-interference performance of the fungal community was higher than that of bacteria.

Conclusion

Our data reveal the characteristics of the soil microbial community during the restoration process of Betula platyphylla Suk secondary forest under different types of disturbance, which is of great significance for understanding the role of soil microorganisms in the forest ecological cycle.
Systematic review and meta-analysis of the effects of menopause hormone therapy on risk of Alzheimer’s disease and dementia
Authors: Nerattini Matilde , Jett Steven , Andy Caroline , Carlton Caroline , Zarate Camila , Boneu Camila , Battista Michael , Pahlajani Silky , Loeb-Zeitlin Susan , Havryulik Yelena , Williams Schantel , Christos Paul , Fink Matthew , Brinton Roberta Diaz , Mosconi Lisa
Published: October 2023

Introduction

Despite a large preclinical literature demonstrating neuroprotective effects of estrogen, use of menopausal hormone therapy (HT) for Alzheimer’s disease (AD) risk reduction has been controversial. Herein, we conducted a systematic review and meta-analysis of HT effects on AD and dementia risk.

Methods

Our systematic search yielded 6 RCT reports (21,065 treated and 20,997 placebo participants) and 45 observational reports (768,866 patient cases and 5.5 million controls). We used fixed and random effect meta-analysis to derive pooled relative risk (RR) and 95% confidence intervals (C.I.) from these studies.

Results

Randomized controlled trials conducted in postmenopausal women ages 65 and older show an increased risk of dementia with HT use compared with placebo [RR = 1.38, 95% C.I. 1.16–1.64, p < 0.001], driven by estrogen-plus-progestogen therapy (EPT) [RR = 1.64, 95% C.I. 1.20–2.25, p = 0.002] and no significant effects of estrogen-only therapy (ET) [RR = 1.19, 95% C.I. 0.92–1.54, p = 0.18]. Conversely, observational studies indicate a reduced risk of AD [RR = 0.78, 95% C.I. 0.64–0.95, p = 0.013] and all-cause dementia [RR = .81, 95% C.I. 0.70–0.94, p = 0.007] with HT use, with protective effects noted with ET [RR = 0.86, 95% C.I. 0.77–0.95, p = 0.002] but not with EPT [RR = 0.910, 95% C.I. 0.775–1.069, p = 0.251]. Stratified analysis of pooled estimates indicates a 32% reduced risk of dementia with midlife ET [RR = 0.685, 95% C.I. 0.513–0.915, p = 0.010] and non-significant reductions with midlife EPT [RR = 0.775, 95% C.I. 0.474–1.266, p = 0.309]. Late-life HT use was associated with increased risk, albeit not significant [EPT: RR = 1.323, 95% C.I. 0.979–1.789, p = 0.069; ET: RR = 1.066, 95% C.I. 0.996–1.140, p = 0.066].

Discussion

These findings support renewed research interest in evaluating midlife estrogen therapy for AD risk reduction.
Lightweight semantic segmentation network with configurable context and small object attention
Authors: Zhang Chunyu , Xu Fang , Wu Chengdong , Li Jinzhao
Published: October 2023

The current semantic segmentation algorithms suffer from encoding feature distortion and small object feature loss. Context information exchange can effectively address the feature distortion problem, but it has the issue of fixed spatial range. Maintaining the input feature resolution can reduce the loss of small object information but would slow down the network’s operation speed. To tackle these problems, we propose a lightweight semantic segmentation network with configurable context and small object attention (CCSONet). CCSONet includes a long-short distance configurable context feature enhancement module (LSCFEM) and a small object attention decoding module (SOADM). The LSCFEM differs from the regular context exchange module by configuring long and short-range relevant features for the current feature, providing a broader and more flexible spatial range. The SOADM enhances the features of small objects by establishing correlations among objects of the same category, avoiding the introduction of redundancy issues caused by high-resolution features. On the Cityscapes and Camvid datasets, our network achieves the accuracy of 76.9 mIoU and 73.1 mIoU, respectively, while maintaining speeds of 87 FPS and 138 FPS. It outperforms other lightweight semantic segmentation algorithms in terms of accuracy.
The relationship between cognition and white matter tract damage after mild traumatic brain injury in a premorbidly healthy, hospitalised adult cohort during the post-acute period
Authors: Anderson Jacqueline F. I. , Oehr Lucy E. , Chen Jian , Maller Jerome J. , Seal Marc L. , Yang Joseph Yuan-Mou
Published: October 2023

Introduction

Recent developments in neuroimaging techniques enable increasingly sensitive consideration of the cognitive impact of damage to white matter tract (WMT) microstructural organisation after mild traumatic brain injury (mTBI).

Objective

This study investigated the relationship between WMT microstructural properties and cognitive performance.

Participants, setting and design

Using an observational design, a group of 26 premorbidly healthy adults with mTBI and a group of 20 premorbidly healthy trauma control (TC) participants who were well-matched on age, sex, premorbid functioning and a range of physical, psychological and trauma-related variables, were recruited following hospital admission for traumatic injury.

Main measures

All participants underwent comprehensive unblinded neuropsychological examination and structural neuroimaging as outpatients 6–10 weeks after injury. Neuropsychological examination included measures of speed of processing, attention, memory, executive function, affective state, pain, fatigue and self-reported outcome. The WMT microstructural properties were estimated using both diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) modelling techniques. Tract properties were compared between the corpus callosum, inferior longitudinal fasciculus, uncinate fasciculus, anterior corona radiata and three segmented sections of the superior longitudinal fasciculus.

Results

For the TC group, in all investigated tracts, with the exception of the uncinate fasciculus, two DTI metrics (fractional anisotropy and apparent diffusion coefficient) and one NODDI metric (intra-cellular volume fraction) revealed expected predictive linear relationships between extent of WMT microstructural organisation and processing speed, memory and executive function. The mTBI group showed a strikingly different pattern relative to the TC group, with no relationships evident between WMT microstructural organisation and cognition on most tracts.

Conclusion

These findings indicate that the predictive relationship that normally exists in adults between WMT microstructural organisation and cognition, is significantly disrupted 6–10 weeks after mTBI and suggests that WMT microstructural organisation and cognitive function have disparate recovery trajectories.
Blood-based biomarkers: diagnostic value in brain tumors (focus on gliomas)
Authors: Yang Yuting , Hu Fei , Wu Song , Huang Zhangliang , Wei Kun , Ma Yuan , Ou-Yang Qing
Published: October 2023

Background

Brain tumors, especially gliomas, are known for high lethality. It is currently understood that the correlations of tumors with coagulation and inflammation have been gradually revealed.

Objective

This study aimed to explore the potential value of several reported peripheral blood parameters as comprehensively as possible, with preoperative diagnosis and identification of brain tumors (focus on gliomas).

Methods

Patients with central nervous system tumors (craniopharyngioma, ependymoma, spinal meningioma, acoustic neuroma, brain metastases, meningioma, and glioma) or primary trigeminal neuralgia admitted to our hospital were retrospectively analyzed. The results of the routine coagulation factor test, serum albumin test, and blood cell test in peripheral blood were recorded for each group of patients on admission. Neutrophil–lymphocyte ratio (NLR), derived NLR (dNLR), platelet–lymphocyte ratio (PLR), lymphocyte–monocyte ratio (LMR), prognostic nutritional index (PNI), the systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), and their pairings were calculated. Their ability to identify brain tumors and their correlation with glioma grade were analyzed.

Results

A total of 698 patients were included in this retrospective case–control study. Glioma patients had higher NLR, SII, and PIV but lower LMR. The NLR in the brain metastasis group was lower than that in the control, meningioma, and acoustic neuroma groups, but the SII and PIV were higher than those in the ependymoma group. Fibrinogen, white blood cell count, neutrophil count, NLR, SII, and PIV in the GBM group were higher than those in the control group. In all comparisons, NLR and NLR + dNLR showed the greatest accuracy, with areas under the curve (AUCs) of 0.7490 (0.6482–0.8498) and 0.7481 (0.6457–0.8505), respectively. PIV, dNLR + PIV, and LMR + PIV ranked second, with AUCs of 0.7200 (0.6551–0.7849), 0.7200 (0.6526–0.7874), 0.7204 (0.6530–0.7878) and 0.7206 (0.6536–0.7875), respectively.

Conclusion

NLR, PIV, and their combinations show high sensitivity and specificity in the diagnosis of brain tumors, especially gliomas. Overall, our results provide evidence for these convenient and reliable peripheral blood markers.
Antibody-recognizing residues 188-211 of TMEM106B exhibit immunohistochemical reactivity with the TMEM106B C-terminal fragment
Authors: Ishikawa Ruoyi , Yamazaki Yu , Nakamori Masahiro , Takahashi Tetsuya , Maruyama Hirofumi
Published: October 2023

Accumulation of TMEM106B fibrils composed of cleaved C-terminal fragments (CTF) of transmembrane protein 106B (TMEM106B) has recently been observed in the brains of elderly subjects and individuals with neurodegenerative diseases. To date, one antibody recognizing the residues 239-250 has been found to display immunoreactivity to the TMEM106B CTF, thereby defining TMEM106B C-terminal immunoreactive (TMEM-ir) material. Immunohistochemical characterization of the CTF using antibodies targeting different immunogens could further shed light on the attributes of TMEM-ir material and the biological relevance of TMEM106B fibril accumulation in vivo. Therefore, we generated and validated five polyclonal antibodies against distinct CTF immunogens, namely the residues 140-163, 164-187, 188-211, 239-250, and 253-274. The antibody recognizing the residues 239-250 (antibody no. 5: 239-250) was employed to identify cases positive for TMEM-ir material. Among the remaining four antibodies, antibody no. 3: 188-211 exhibited significant immunoreactivity in TMEM-ir material-positive cases. Comparative analyzes indicated that antibody no. 3: 188-211 and antibody no. 5: 239-250 likely recognized the same TMEM-ir material. The TMEM-ir material detected by antibody no. 3: 188-211 was observed across multiple brain cell types without co-localization with other pathogenic proteins. In conclusion, our findings suggest that the antibody recognizing the residues 188-211 displays immunohistochemical reactivity to TMEM-ir material. Therefore, in addition to the established antibody recognizing the residues 239-250, the antibody recognizing the residues 188-211 can potentially be used in immunohistochemical studies to further elucidate the significance of CTF accumulation in the brain.
New insights on clinical perspectives of FLASH radiotherapy: from low- to very high electron energy
Authors: Ursino Stefano , Gadducci Giovanni , Giannini Noemi , Gonnelli Alessandra , Fuentes Taiushia , Di Martino Fabio , Paiar Fabiola
Published: October 2023

Radiotherapy (RT) is performed in approximately 75% of patients with cancer, and its efficacy is often hampered by the low tolerance of the surrounding normal tissues. Recent advancements have demonstrated the potential to widen the therapeutic window using “very short” radiation treatment delivery (from a conventional dose rate between 0.5 Gy/min and 2 Gy/min to more than 40 Gy/s) causing a significant increase of normal tissue tolerance without varying the tumor effect. This phenomenon is called “FLASH Effect (FE)” and has been discovered by using electrons. Although several physical, dosimetric, and radiobiological aspects need to be clarified, current preclinical “in vivo” studies have reported a significant protective effect of FLASH RT on neurocognitive function, skin toxicity, lung fibrosis, and bowel injury. Therefore, the current radiobiological premises lay the foundation for groundbreaking potentials in clinical translation, which could be addressed to an initial application of Low Energy Electron FLASH (LEE) for the treatment of superficial tumors to a subsequent Very High Energy Electron FLASH (VHEE) for the treatment of deep tumors. Herein, we report a clinical investigational scenario that, if supported by preclinical studies, could be drawn in the near future.
Cranial radiation therapy with hippocampus avoidance in lung cancer treatment: systematic review and meta-analysis
Authors: Zheng Yue , You Liting , Feng Baijie , Tang Min , Na Feifei
Published: October 2023

Background

The role of cranial radiation therapy with hippocampus avoidance (HA-CRT) in neurocognitive function (NCF), brain metastasis (BM), and overall survival (OS) in lung cancer remains unclear.

Methods

A meta-analysis was conducted to evaluate the impact of HA-CRT in lung cancer. Data from studies on hippocampal-avoidance prophylactic cranial irradiation (HA-PCI) and whole brain radiotherapy (HA-WBRT) were pooled.

Results

A total of 14 studies, including 5 randomized controlled trials, were included. The focus of NCF was mainly via the Hopkins Verbal Learning Test—Revised or the Free and Cued Selective Reminding Test. At 6 months post-radiotherapy, the pooled proportion of participants with decline in the performance of total recall, delayed recall, and discrimination in neurocognitive tests were 0.22 (95% CI 0.15, 0.29), 0.20 (95% CI 0.13, 0.27), and 0.14 (95% CI 0.05, 0.24) respectively. After 12 months, the proportion were 0.16 (95% CI 0.08, 0.23), 0.10 (95% CI 0.04, 0.16), and 0.04 (95% CI 0, 0.09) respectively. For HA zone relapse, the RR of HA-CRT versus CRT was 2.72 (95% CI 0.53, 13.87), and for 2-year BM, it was 1.20 (95% CI 0.82, 1.75). Regarding HA-PCI in SCLC, the 1-year BM rate was 0.12 (95% CI 0.07, 0.17), and the 2-year BM rate was 0.20 (95% CI 0.16, 0.25). For HA-WBRT in NSCLC with BM, the 2-year intracranial progression rate was 0.38 (95% CI 0.13, 0.62). There was no significant difference in OS between HA-CRT and CRT.

Conclusions

HA-CRT appears to be safe in lung cancer, but it may not outperform conventional CRT. Larger RCTs comparing HA-CRT and CRT are warranted.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022360890, identifier CRD42022360890.
Psychometric properties of the Sport Anxiety Scale-2 for Chinese adolescent athletes taking the National Sports College Entrance Examination
Authors: Li Shichen , Tang Changfa , Guo Cheng , Bu Te
Published: October 2023

Background

This study aims to evaluate the psychometric properties of the Sport Anxiety Scale-2 (SAS-2) in Chinese adolescent sports exam candidates.

Methods

One day before the National Sports College Entrance Examination, 965 Chinese athletes rated the Chinese-language SAS-2. Confirmatory factor analysis was performed to test the three-factor structure. Factorial invariance was tested by comparing the configural invariance model to three more constrained models. Construct validity and reliability were determined.

Results

Fit indices meet the critical values: CFI = 0.953, TLI = 0.943, RMSEA = 0.048 [90% CI, 0.041–0.054], and SRMR = 0.042. All path factor loadings exceed 0.5. The changes in CFI and RMSEA across the configural, metric, scalar, and uniqueness invariance are within the critical values, demonstrating strict measurement invariance across gender, years of training, and type of sports. The average variance extracted of the worry sub-scale is above the cutoff criteria, and McDonald's omega coefficients are over 0.70. Significant correlations exist between the SAS-2, SCAT, and CSAI-2. Factor correlations are all below 0.8. The measurement also distinguishes the known gender effect, with females showing a probability of 58.6% higher anxiety levels. The intraclass correlation coefficient ranges from 0.706 to 0.801.

Conclusion

This study validated the Chinese-language SAS-2 in measuring competitive anxiety among Chinese adolescent athletes taking the National Sports College Entrance Examination. The development of the scale's applicability in China is discussed.
Mechanical ventilation induces brainstem inflammation in preterm fetal sheep
Authors: Vidinopoulos Kayla , Azman Zahrah , Somers Ainsley , Zahra Valerie A. , Thiel Alison , Lu Hui , Pham Yen , Tran Nhi Thao , Allison Beth J. , Herlenius Eric , Hooper Stuart , Galinsky Robert , Polglase Graeme R.
Published: October 2023

Background

Preterm infants have immature respiratory drive and often require prolonged periods of mechanical ventilation. Prolonged mechanical ventilation induces systemic inflammation resulting in ventilation-induced brain injury, however its effect on brainstem respiratory centers is unknown. We aimed to determine the effects of 24 h of mechanical ventilation on inflammation and injury in brainstem respiratory centres of preterm fetal sheep.

Methods

Preterm fetal sheep at 110 ± 1 days (d) gestation were instrumented to provide mechanical ventilation in utero. At 112 ± 1 d gestation, fetuses received either mechanical ventilation (VENT; n = 7; 3 ml/kg) for 24 h, or no ventilation (CONT; n = 6). At post-mortem, fetal brainstems were collected for assessment of mRNA and histological markers of inflammation and injury.

Results

In utero ventilation (IUV) did not alter any blood-gas parameters. IUV significantly increased systemic IL-6 and IL-8 concentrations over the 24 h period compared to CONT. The number of ameboid microglia within the nucleus tractus solitarius and the raphe nucleus increased in VENT fetuses (p < 0.05 for both vs. control). The % area fraction of GFAP + staining was not significantly higher within the preBötzinger complex (p = 0.067) and retrotrapezoid nucleus and parafacial respiratory group (p = 0.057) in VENT fetuses compared to CONT. Numbers of caspase-3 and TUNEL-positive cells were similar between groups. Gene expression (mRNA) levels of inflammation, injury, cell death and prostaglandin synthesis within the brainstem were similar between groups.

Conclusion

Mechanical ventilation induces a systemic inflammatory response with only moderate inflammatory effects within the brainstem respiratory centres of preterm fetal sheep.
Non-aromatizable androgens modulate the lipopolysaccharide induced expression of the P2X7 receptor in human adipocytes
Authors: Di Vincenzo Angelo , Granzotto Marnie , Crescenzi Marika , Vettor Roberto , Rossato Marco
Published: October 2023

Introduction: The activation of the P2X7 receptor subtype (P2X7R) has a main role in orchestrating the cellular inflammatory response in many different tissues. Obesity is characterized by dysfunctional fat deposition leading to a tissue-specific and systemic low-grade inflammation. Androgens and estrogens contribute to the whole adipose tissue inflammatory state, but the involvement of sex steroids in the purinergic signaling modulation in adipocytes is still unknown.

Methods: We performed an in vitro study to evaluate the possible role of sex hormones on the P2X7R gene expression in human adipocytes, at baseline and after stimulation with bacterial lipopolysaccharide (LPS). We evaluated P2X7R gene expression during in vitro differentiation of human adipocytes, in the absence and presence of testosterone (T) and 17β-estradiol (E2) in the presence and absence of LPS. Furthermore, we analyzed the effects of incubation with dihydrotestosterone (DHT), a non-aromatizable androgen, using the co-incubation of isolated human adipocytes with T alone or in combination with anastrozole, an inhibitor of aromatase, the enzyme responsible of T conversion to E2.

Results: At baseline, incubation of adipocytes with T or E2 did not significantly affect P2X7R gene expression. On the contrary, the incubation with DHT was associated with a significant reduction of P2X7R gene expression. LPS incubation significantly increased gene expression of P2X7R with respect to baseline. Interestingly, after LPS stimulation, DHT exposure showed an additional effect, markedly increasing the P2X7R gene expression. This amplificatory effect was confirmed by the incubation of adipocytes to both anastrozole and testosterone. In these experimental conditions, while no effect was observed at baseline, an amplification of the expression of the P2X7R mRNA was observed after stimulation with LPS.

Discussion: The purinergic system is involved in the inflammatory response of adipocytes, and androgens may modulate its activity. In particular DHT, a non-aromatizable androgen, amplifies the LPS-induced P2X7R gene expression in human adipocytes thus showing a gender regulated response of the expression of this purinergic receptor strongly involved in the inflammatory response in adipose tissue.
Effect of crop rotational position and nitrogen supply on root development and yield formation of winter wheat
Authors: Arnhold Jessica , Grunwald Dennis , Braun-Kiewnick Andrea , Koch Heinz-Josef
Published: October 2023

The lower yield of wheat grown after wheat (second wheat) compared with the first wheat after a break crop is frequently attributed to fungal disease occurrence, but has also been found without visible disease infection; thus, other factors might be responsible for the lower yield of the second wheat. The aims of this study were to analyze the effects of growing wheat as first and second wheat after oilseed rape, as well as monoculture in a long-term field experiment over three years on (i) aboveground biomass formation, root development and nutrient acquisition during the growing season, (ii) take-all occurrence, and (iii) grain yield and yield components. Subsoil root length density of winter wheat was significantly higher after oilseed rape as pre-crop than after wheat, which was independent of take-all occurrence. Differences in wheat aboveground biomass occurred at early growth stages and were persistent until harvest. Grain yield loss correlated well with take-all disease severity in a wet year but yield differences among crop rotational positions occurred also in a dry year without visible fungal infection. Thus, an effect of the crop rotational position of wheat beyond take-all disease pressure can be assumed. Overall, wheat root length density might be the key to understand wheat biomass formation and grain yield in different crop rotational positions.
Accumulation of colicin M protein and its biological activity in transgenic lettuce and mizuna plants
Authors: Shcherbak Nataliia , Prochaska Heike , Lystvan Kateryna , Prokhorova Yelizaveta , Giritch Anatoli , Kuchuk Mykola
Published: October 2023

Food-borne illnesses caused by pathogenic Escherichia coli strains, especially enterohaemorrhagic E. coli (EHEC), are a serious public health problem, as debilitating disease and even death from such food poisonings have been repeatedly reported. Colicin M (ColM), a non-antibiotic antimicrobial protein produced by some strains of E. coli, has shown promising activity in controlling multiple enteropathogenic strains of E. coli and related pathogens. As contaminated green leafy vegetables are a frequent source of pathogenic E. coli infections, we genetically modified (GM) two edible crops, lettuce (Lactuca sativa L.) and mizuna (Brassica rapa subsp. nipposinica var. laciniata), to stably express the ColM gene and assessed the antibacterial activity of tissue extracts from these plants against selected E. coli strains in vitro. Transgenic plants of these species were developed using Agrobacterium-mediated transformation with a vector containing the ColM-coding gene (cma) under the control of the 35S promoter. Western blot analysis of recombinant ColM protein was performed in selected transgenic plants to confirm cma gene expression and quantify ColM accumulation. Extracts of transgenic plants expressing ColM showed significant activity against two major strains of EHEC (O157:H7 and O104:H4) as well as E. coli strains resistant to beta-lactam- and carbapenem-class antibiotics. Importantly, the antibacterial activity persisted in several subsequent generations of transgenic lettuce and mizuna plants that stably expressed the ColM gene. In addition, our results also show that the antibacterial activity of dried (up to 40°C) biomass of transgenic plants remained stable without a decrease for at least three months.
Rice seed vigor detection based on near-infrared hyperspectral imaging and deep transfer learning
Authors: Qi Hengnian , Huang Zihong , Sun Zeyu , Tang Qizhe , Zhao Guangwu , Zhu Xuhua , Zhang Chu
Published: October 2023

Vigor is one of the important factors that affects rice yield and quality. Rapid and accurate detection of rice seed vigor is of great importance for rice production. In this study, near-infrared hyperspectral imaging technique and transfer learning were combined to detect rice seed vigor. Four varieties of artificial-aged rice seeds (Yongyou12, Yongyou1540, Suxiangjing100, and Longjingyou1212) were studied. Different convolutional neural network (CNN) models were built to detect the vigor of the rice seeds. Two transfer strategies, fine-tuning and MixStyle, were used to transfer knowledge among different rice varieties for vigor detection. The experimental results showed that the convolutional neural network model of Yongyou12 classified the vigor of Yongyou1540, Suxiangjing100, and Longjingyou1212 through MixStyle transfer knowledge, and the accuracy reached 90.00%, 80.33%, and 85.00% in validation sets, respectively, which was better or close to the initial modeling performances of each variety. MixStyle statistics are based on probabilistic mixed instance-level features of cross-source domain training samples. When training instances, new domains can be synthesized, which increases the domain diversity of the source domain, thereby improving the generalization ability of the trained model. This study would help rapid and accurate detection of a large varieties of crop seeds.
Improving the greenness of enterprise supply chains by designing government subsidy mechanisms: based on prospect theory and evolutionary games
Authors: Hou Li , Zhang Yiming , Wu Chunlin , Song Jinbo
Published: October 2023

Fostering sustainable development through green supply chains is of paramount significance. Government subsidies emerge as a successful strategy for motivating businesses to actively participate in such eco-friendly practices. This study employs prospect theory and an evolutionary game model to analyze the transition toward carbon peaking and neutrality while promoting the expansion of highly sustainable businesses. By exploring the decision-making processes of businesses and governments regarding sustainability, we develop an evolutionary game-based decision model to assess the impact of government subsidies on businesses engaged in green supply chains. Through numerical simulation obtained via MATLAB, we examine various factors influencing the evolution of the game system between green supply chain businesses and the government. Additionally, we investigate how government incentives impact the decision-making behavior of green supply chain businesses. Our findings indicate that governmental fines can effectively encourage the adoption of green supply chains. Furthermore, moderate government subsidies incentivize enterprises to opt for sustainable supply chains, benefiting both the government and businesses. However, providing hefty government subsidies not only fails to encourage the adoption of green supply chains but also incurs costs for the government, without yielding any positive change in the businesses’ approach. By incorporating evolutionary game theory and prospect theory, this study contributes to the body of knowledge on government-supported green supply chains, offering incentive programs tailored to the real-world conditions faced by businesses while demonstrating practical application values.
Universal prevention for non-suicidal self-injury in adolescents is scarce - A systematic review
Authors: Bürger Arne , von Schoenfeld Cornelia , Scheiner Christin , Seidel Alexandra , Wasserscheid Antonia , Gad Doreya , Kittel-Schneider Sarah , Romanos Marcel , Reiter Andrea M. F.
Published: October 2023

Non-suicidal self-injury (NSSI) during adolescence is a high-risk marker for the development and persistence of mental health problems and has been recognized as a significant public health problem. Whereas targeted prevention has indeed shown to be effective in reducing NSSI and improve mental health problems, access to such programs is limited. By face validity, universal prevention of NSSI seems an ideal starting point for a stepped-care model to circumvent a lack of resources in the medical care system. However, it is yet unclear how effective such approaches are. Here, we provide a summary of existing work on universal prevention of NSSI in adolescents younger than 21 years based on a systematic literature search. We found that only seven studies are available. None of the programs evaluated was found to be effective in reducing the incidence or frequency of NSSI. After providing a comprehensive summary of the existing work, we evaluate the fact that existing work primarily focusses on selected/targeted prevention and on psychoeducational methods. We derive implications for future directions in the field of universal prevention of NSSI.