bluuebunny/crossref_metadata_2025 huggingface dataset:
CD44v6 specific CAR-NK cells for targeted immunotherapy of head and neck squamous cell carcinoma
Authors: Ciulean Ioana Sonya , Fischer Joe , Quaiser Andrea , Bach Christoph , Abken Hinrich , Tretbar Uta Sandy , Fricke Stephan , Koehl Ulrike , Schmiedel Dominik , Grunwald Thomas
Published: November 2023

Head and neck squamous cell carcinoma (HNSCC) is a major challenge for current therapies. CAR-T cells have shown promising results in blood cancers, however, their effectiveness against solid tumors remains a hurdle. Recently, CD44v6-directed CAR-T cells demonstrated efficacy in controlling tumor growth in multiple myeloma and solid tumors such as HNSCC, lung and ovarian adenocarcinomas. Apart from CAR-T cells, CAR-NK cells offer a safe and allogenic alternative to autologous CAR-T cell therapy. In this paper, we investigated the capacity of CAR-NK cells redirected against CD44v6 to execute cytotoxicity against HNSCC. Anti-CD44v6 CAR-NK cells were generated from healthy donor peripheral blood-derived NK cells using gamma retroviral vectors (gRVs). The NK cell transduction was optimized by exploring virus envelope proteins derived from the baboon endogenous virus envelope (BaEV), feline leukemia virus (FeLV, termed RD114-TR) and gibbon ape leukemia virus (GaLV), respectively. BaEV pseudotyped gRVs induced the highest transduction rate compared to RD114-TR and GaLV envelopes as measured by EGFP and surface CAR expression of transduced NK cells. CAR-NK cells showed a two- to threefold increase in killing efficacy against various HNSCC cell lines compared to unmodified, cytokine-expanded primary NK cells. Anti-CD44v6 CAR-NK cells were effective in eliminating tumor cell lines with high and low CD44v6 expression levels. Overall, the improved cytotoxicity of CAR-NK cells holds promise for a therapeutic option for the treatment of HNSCC. However, further preclinical trials are necessary to test in vivo efficacy and safety, as well to optimize the treatment regimen of anti-CD44v6 CAR-NK cells against solid tumors.
A novel prognostic classification integrating lipid metabolism and immune co-related genes in acute myeloid leukemia
Authors: Li Ding , Wu Xuan , Cheng Cheng , Liang Jiaming , Liang Yinfeng , Li Han , Guo Xiaohan , Li Ruchun , Zhang Wenzhou , Song Wenping
Published: November 2023

Background

As a severe hematological malignancy in adults, acute myeloid leukemia (AML) is characterized by high heterogeneity and complexity. Emerging evidence highlights the importance of the tumor immune microenvironment and lipid metabolism in cancer progression. In this study, we comprehensively evaluated the expression profiles of genes related to lipid metabolism and immune modifications to develop a prognostic risk signature for AML.

Methods

First, we extracted the mRNA expression profiles of bone marrow samples from an AML cohort from The Cancer Genome Atlas database and employed Cox regression analysis to select prognostic hub genes associated with lipid metabolism and immunity. We then constructed a prognostic signature with hub genes significantly related to survival and validated the stability and robustness of the prognostic signature using three external datasets. Gene Set Enrichment Analysis was implemented to explore the underlying biological pathways related to the risk signature. Finally, the correlation between signature, immunity, and drug sensitivity was explored.

Results

Eight genes were identified from the analysis and verified in the clinical samples, including APOBEC3C, MSMO1, ATP13A2, SMPDL3B, PLA2G4A, TNFSF15, IL2RA, and HGF, to develop a risk-scoring model that effectively stratified patients with AML into low- and high-risk groups, demonstrating significant differences in survival time. The risk signature was negatively related to immune cell infiltration. Samples with AML in the low-risk group, as defined by the risk signature, were more likely to be responsive to immunotherapy, whereas those at high risk responded better to specific targeted drugs.

Conclusions

This study reveals the significant role of lipid metabolism- and immune-related genes in prognosis and demonstrated the utility of these signature genes as reliable bioinformatic indicators for predicting survival in patients with AML. The risk-scoring model based on these prognostic signature genes holds promise as a valuable tool for individualized treatment decision-making, providing valuable insights for improving patient prognosis and treatment outcomes in AML.
Composites of CoFe2O4/Graphene oxide/Kaolinite for adsorption of lead ion from aqueous solution
Authors: Daniel Reta Yared , Desissa Temesgen Debelo
Published: November 2023

In this work, we established composites from kaolinite (K), CoFe2O4 (CF), and graphene oxide (GO) for the adsorption of the lead ion (Pb (II)). Initially, a composite of CF-GO was synthesized by hydrothermal method using cellulose bio-template extracted from false banana. The weight ratio of GO varied from 0.20 to 0.30, i.e., (1-x) CF/(x)GO (x = 0.20, 0.25, 0.30). The sample with x = 0.30, i.e., CF-0.3GO exhibited a better adsorption capacity of about 23.6 mg g−1 from the binary composite samples at the initial Pb concentration of 50 mg L−1. Then, the contact time and adsorbent dosage of CF-0.3GO were optimized with the corresponding results of 90 min and 1.2 g L−1, respectively. A ternary composite was formulated from the sample of CF-0.3GO and Kaolinite (K) with the nominal composition of (1-y)K/(y)(CF-0.3GO), where y = 0.30, 0.45, 0.60, and 0.75. Among the ternary composites, the sample with a composition of 0.25K/0.75(CF0-0.3GO) showed the best adsorption capacity of about 4.2 mg g−1 at the initial Pb concentration of 10 mg L−1, and this sample was subsequently selected for further studies. The synthesized composites were characterized using powder X-ray diffraction (XRD), Scanning electron microscopy (SEM), Fourier transforms infrared spectroscopy (FTIR), and Differential thermogravimetric analysis (TGA-DTA), Brunauer-Emmett-Teller (BET), respectively, to determine phase purity, the particles morphology, functional groups, thermal stability, and surface area and pore volume of the of samples. Atomic absorption spectroscopy (AAS) was used to determine the adsorption capacity of samples. The effect of pH ranging from 2 to 10 was investigated for the present composite. At pH of 4, the adsorption capacity and removal efficiency changed significantly, with the corresponding results of 6.62 mg g−1 and 99 %, respectively, and becomes constant. Adsorption isotherms and kinetics were investigated for a composite with a composition of 0.25K/0.75 (CF-0.3GO). The Freundlich isotherm model best fits the adsorption isotherm, with a correlation coefficient of 0.93, and the kinetic behavior followed Pseudo-second-order adsorption kinetics. Finally, the synthesized composite was stable for three-round tests toward the Pb(II) removal. Therefore, the results of this study indicate that the composites of CoFe2O4/Graphene oxide/Kaolinite could be a potential candidate for the removal of Pb (II) ions.
Hot-injection synthesis of lead-free pseudo-alkali metal-based perovskite (TlSnX3) nanoparticles with tunable optical properties
Authors: Kim Wooyeon , Koo Bonkee , Ko Min Jae , Jung Heesuk
Published: November 2023

The commercialization of organo-inorganic hybrid perovskite materials for optoelectronic applications is limited owing to the restriction of lead (Pb) usage in consumer electronics and the instability of organic cations in the perovskite structure. To address these challenges, we synthesize TlSnX3 (X = Cl, Br, and I) perovskite nanoparticles (NPs) with high crystallinity and uniformity using the hot-injection method. The optical properties of TlSnX3 NPs are fine-tuned by substituting the halide ions of TlSnX3. In addition, the oxidation of Sn in TlSnX3 NPs is effectively prevented by the strong reducing ligands such as dioleamide (DOA) and trioctylphosphine (TOP). Furthermore, TlSnX3 NPs-based perovskite solar cells (PSCs) are fabricated by a spin-coating method; they exhibited a high open-circuit voltage (∼1.4 V). These results demonstrate that TlSnX3 NPs can be an attractive candidate for solution-processable optoelectronic devices.
Responses of a soil fungal community to severe windstorm damages in an old silver fir stand
Authors: Venice Francesco , Vizzini Alfredo , Danti Roberto , Della Rocca Gianni , Mello Antonietta
Published: November 2023

Forests are increasingly threatened by climate change and the Anthropocene seems to have favored the emergence and adaptation of pathogens. Robust monitoring methods are required to prevent biodiversity and ecosystems losses, and this imposes the choice of bioindicators of habitat health. Fungal communities are increasingly recognized as fundamental components in nearly all natural and artificial environments, and their ecosystem services have a huge impact in maintaining and restoring the functionality of ecosystems. We coupled metabarcoding and soil analyses to infer the dynamics of a fungal community inhabiting the old silver fir stand in Vallombrosa (Italy), which is known to be afflicted by both Armillaria and Annosum root rot. The forest was affected in 2015, by a windstorm which caused a partial falling and uprooting of trees. The remaining stand, not affected by the windstorm, was used as a comparison to infer the consequences of the ecosystem disturbance. We demonstrated that the abundance of pathogens alone is not able to explain the soil fungal differences shown by the two areas. The fungal community as a whole was equally rich in the two areas, even if a reduction of the core ectomycorrhizal mycobiome was observed in the wind-damaged area, accompanied by the increase of wood saprotrophs and arbuscular mycorrhizas. We hypothesize a reshaping of the fungal community and a potentially ongoing re-generation of its functionalities. Our hypothesis is driven by the evidence that key symbiotic, endophytic, and saprotrophic guilds are still present and diversified in the wind-damaged area, and that dominance of single taxa or biodiversity loss was not observed from a mycological point of view. With the present study, we aim at providing evidence that fungal communities are fundamental for the monitoring and the conservation of threatened forest ecosystems.
Combined genomic-proteomic approach in the identification of Campylobacter coli amoxicillin-clavulanic acid resistance mechanism in clinical isolates
Authors: Deforet Francis , Jehanne Quentin , Bénéjat Lucie , Aptel Johanna , Prat Roxane , Desbiolles Chloé , Ducournau Astrid , Jauvain Marine , Bonnet Richard , Vandenesch François , Lemoine Jérôme , Lehours Philippe
Published: November 2023

Introduction

Aminopenicillins resistance among Campylobacter jejuni and Campylobacter coli strains is associated with a single mutation in the promoting region of a chromosomal beta-lactamase blaOXA61, allowing its expression. Clavulanic acid is used to restore aminopenicillins activity in case of blaOXA61 expression and has also an inherent antimicrobial activity over Campylobacter spp. Resistance to amoxicillin-clavulanic acid is therefore extremely rare among these species: only 0.1% of all Campylobacter spp. analyzed in the French National Reference Center these last years (2017–2022).

Material and methods

Whole genome sequencing with bioinformatic resistance identification combined with mass spectrometry (MS) was used to identify amoxicillin-acid clavulanic resistance mechanism in Campylobacters.

Results

A G57T mutation in blaOXA61 promoting region was identified in all C. jejuni and C. coli ampicillin resistant isolates and no mutation in ampicillin susceptible isolates. Interestingly, three C. coli resistant to both ampicillin and amoxicillin-clavulanic acid displayed a supplemental deletion in the promoting region of blaOXA61 beta-lactamase, at position A69. Using MS, a significant difference in the expression of BlaOXA61 was observed between these three isolates and amoxicillin-clavulanic acid susceptible C. coli.

Conclusion

A combined genomics/proteomics approach allowed here to identify a rare putative resistance mechanism associated with amoxicillin-clavulanic acid resistance for C. coli.
Unidirectional gene pairs in archaea and bacteria require overlaps or very short intergenic distances for translational coupling via termination-reinitiation and often encode subunits of heteromeric complexes
Authors: Huber Madeleine , Vogel Nico , Borst Andreas , Pfeiffer Friedhelm , Karamycheva Svetlana , Wolf Yuri I. , Koonin Eugene V. , Soppa Jörg
Published: November 2023

Genomes of bacteria and archaea contain a much larger fraction of unidirectional (serial) gene pairs than convergent or divergent gene pairs. Many of the unidirectional gene pairs have short overlaps of −4 nt and −1 nt. As shown previously, translation of the genes in overlapping unidirectional gene pairs is tightly coupled. Two alternative models for the fate of the post-termination ribosome predict either that overlaps or very short intergenic distances are essential for translational coupling or that the undissociated post-termination ribosome can scan through long intergenic regions, up to hundreds of nucleotides. We aimed to experimentally resolve the contradiction between the two models by analyzing three native gene pairs from the model archaeon Haloferax volcanii and three native pairs from Escherichia coli. A two reporter gene system was used to quantify the reinitiation frequency, and several stop codons in the upstream gene were introduced to increase the intergenic distances. For all six gene pairs from two species, an extremely strong dependence of the reinitiation efficiency on the intergenic distance was unequivocally demonstrated, such that even short intergenic distances of about 20 nt almost completely abolished translational coupling. Bioinformatic analysis of the intergenic distances in all unidirectional gene pairs in the genomes of H. volcanii and E. coli and in 1,695 prokaryotic species representative of 49 phyla showed that intergenic distances of −4 nt or −1 nt (= short gene overlaps of 4 nt or 1 nt) were by far most common in all these groups of archaea and bacteria. A small set of genes in E. coli, but not in H. volcanii, had intergenic distances of around +10 nt. Our experimental and bioinformatic analyses clearly show that translational coupling requires short gene overlaps, whereas scanning of intergenic regions by the post-termination ribosome occurs rarely, if at all. Short overlaps are enriched among genes that encode subunits of heteromeric complexes, and co-translational complex formation requiring precise subunit stoichiometry likely confers an evolutionary advantage that drove the formation and conservation of overlapping gene pairs during evolution.
Psoriasis comorbidity management in the COVID era: a pressing challenge
Authors: Song Yang , Yao Lei , Li Shanshan , Zhou Junfeng
Published: November 2023

The global COVID-19 pandemic has presented a significant, ongoing challenge since its emergence in late 2019. Today, the Omicron strain, which is less lethal but more contagious than the original outbreak strain, continues to pose substantial health risks. In this background, the management of psoriatic comorbidities has become even more complex, particularly for patients with underlying inflammatory, metabolic, or cardiovascular diseases. This review aims to summarize current research on comorbid COVID-19 and psoriasis, and provide insights into the development of evidence-based management strategies. By providing appropriate patient instruction, implementing protective measures, and re-evaluating medication prescriptions based on each patient’s unique situation, healthcare professionals can effectively address the challenges faced by patients with comorbid psoriasis in the COVID-19 era.
Unveiling the noncanonical activation mechanism of CDKs: insights from recent structural studies
Authors: Li Tao , Tang Hui-Chi , Tsai Kuang-Lei
Published: November 2023

The Cyclin-dependent kinases (CDKs) play crucial roles in a range of essential cellular processes. While the classical two-step activation mechanism is generally applicable to cell cycle-related CDKs, both CDK7 and CDK8, involved in transcriptional regulation, adopt distinct mechanisms for kinase activation. In both cases, binding to their respective cyclin partners results in only partial activity, while their full activation requires the presence of an additional subunit. Recent structural studies of these two noncanonical kinases have provided unprecedented insights into their activation mechanisms, enabling us to understand how the third subunit coordinates the T-loop stabilization and enhances kinase activity. In this review, we summarize the structure and function of CDK7 and CDK8 within their respective functional complexes, while also describing their noncanonical activation mechanisms. These insights open new avenues for targeted drug discovery and potential therapeutic interventions in various diseases related to CDK7 and CDK8.
Associations between circulating cardiovascular disease risk factors and cognitive performance in cognitively healthy older adults from the NuAge study
Authors: Koblinsky Noah D. , Carmichael Pierre-Hugues , Belleville Sylvie , Fiocco Alexandra J. , Gaudreau Pierrette , Greenwood Carol E. , Kergoat Marie-Jeanne , Morais José A. , Presse Nancy , Laurin Danielle , Ferland Guylaine
Published: November 2023

Introduction

Cardiovascular disease risk factors (CVRFs) contribute to the development of cognitive impairment and dementia.

Methods

This study examined the associations between circulating CVRF biomarkers and cognition in 386 cognitively healthy older adults (mean age = 78 ± 4 years, 53% females) selected from the Quebec Longitudinal Study on Nutrition and Successful Aging (NuAge). Memory, executive function, and processing speed were assessed at baseline and 2-year follow-up. CVRF biomarkers included total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides, glucose, insulin, high sensitivity C-reactive protein (hs-CRP), homocysteine, protein carbonyls, and cortisol. Linear mixed models were used to determine associations between individual CVRF biomarkers and cognition at both time points.

Results

HDL-C was most consistently associated with cognition with higher values related to better performance across several domains. Overall, stronger and more consistent relationships between CVRF biomarkers and cognition were observed in females relative to males.

Discussion

Findings suggest that increases in the majority of circulating CVRFs are not associated with worse cognition in cognitively healthy older adults.
To re-examine the intersection of microglial activation and neuroinflammation in neurodegenerative diseases from the perspective of pyroptosis
Authors: Li Yuan , Li Ying-Jie , Zhu Zhao-Qiong
Published: November 2023

Neurodegenerative diseases (NDs), such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and motor neuron disease, are diseases characterized by neuronal damage and dysfunction. NDs are considered to be a multifactorial disease with diverse etiologies (immune, inflammatory, aging, genetic, etc.) and complex pathophysiological processes. Previous studies have found that neuroinflammation and typical microglial activation are important mechanisms of NDs, leading to neurological dysfunction and disease progression. Pyroptosis is a new mode involved in this process. As a form of programmed cell death, pyroptosis is characterized by the expansion of cells until the cell membrane bursts, resulting in the release of cell contents that activates a strong inflammatory response that promotes NDs by accelerating neuronal dysfunction and abnormal microglial activation. In this case, abnormally activated microglia release various pro-inflammatory factors, leading to the occurrence of neuroinflammation and exacerbating both microglial and neuronal pyroptosis, thus forming a vicious cycle. The recognition of the association between pyroptosis and microglia activation, as well as neuroinflammation, is of significant importance in understanding the pathogenesis of NDs and providing new targets and strategies for their prevention and treatment.
The key role of depression and supramarginal gyrus in frailty: a cross-sectional study
Authors: Isernia Sara , Blasi Valeria , Baglio Gisella , Cabinio Monia , Cecconi Pietro , Rossetto Federica , Cazzoli Marta , Blasi Francesco , Bruckmann Chiara , Giunco Fabrizio , Sorbi Sandro , Clerici Mario , Baglio Francesca
Published: November 2023

Background

The age-related decrease in reserve and resistance to stressors is recognized as frailty, one of the most significant challenges identified in recent years. Despite a well-acknowledged association of frailty with cognitive impairment, depression, and gray matter morphology, no clear data are available regarding the nature of this relationship. This cross-sectional study aims to disentangle the role of the behavioral, neuropsychological, and neural components as predictors or moderators of frailty.

Methods

Ninety-six older adults (mean age = 75.49 ± 6.62) were consecutively enrolled and underwent a clinical and MRI (3 T) evaluation to assess frailty, physical activity, global cognitive level, depression, wellbeing, autonomy in daily living, cortical thickness, and subcortical volumes.

Results

Results showed a full mediation of depression on the link between cortical thickness and frailty, while the cognitive level showed no significant mediating role. In particular, left supramarginal thickness had a predicting role on depression, that in turn impacted frailty occurrence. Finally, handgrip weakness was an early key indicator of frailty in this study’s cohort.

Conclusion

These data substantiate the role of depression in mediating the link between neural integrity of the supramarginal gyrus and frailty. In the complexity of frailty, handgrip weakness seems to be an early key indicator. These results are relevant for the design of rehabilitation interventions aimed at reversing the frail condition.
Cross-modal self-attention mechanism for controlling robot volleyball motion
Authors: Wang Meifang , Liang Zhange
Published: November 2023

Introduction

The emergence of cross-modal perception and deep learning technologies has had a profound impact on modern robotics. This study focuses on the application of these technologies in the field of robot control, specifically in the context of volleyball tasks. The primary objective is to achieve precise control of robots in volleyball tasks by effectively integrating information from different sensors using a cross-modal self-attention mechanism.

Methods

Our approach involves the utilization of a cross-modal self-attention mechanism to integrate information from various sensors, providing robots with a more comprehensive scene perception in volleyball scenarios. To enhance the diversity and practicality of robot training, we employ Generative Adversarial Networks (GANs) to synthesize realistic volleyball scenarios. Furthermore, we leverage transfer learning to incorporate knowledge from other sports datasets, enriching the process of skill acquisition for robots.

Results

To validate the feasibility of our approach, we conducted experiments where we simulated robot volleyball scenarios using multiple volleyball-related datasets. We measured various quantitative metrics, including accuracy, recall, precision, and F1 score. The experimental results indicate a significant enhancement in the performance of our approach in robot volleyball tasks.

Discussion

The outcomes of this study offer valuable insights into the application of multi-modal perception and deep learning in the field of sports robotics. By effectively integrating information from different sensors and incorporating synthetic data through GANs and transfer learning, our approach demonstrates improved robot performance in volleyball tasks. These findings not only advance the field of robotics but also open up new possibilities for human-robot collaboration in sports and athletic performance improvement. This research paves the way for further exploration of advanced technologies in sports robotics, benefiting both the scientific community and athletes seeking performance enhancement through robotic assistance.
Effect of magnesium sulfate on cerebral vasospasm in the treatment of aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis
Authors: Zheng Hanlin , Guo Xiumei , Huang Xinyue , Xiong Yu , Gao Wen , Ke Chuhan , Chen Chunhui , Pan Zhigang , Ye Lichao , Wang Lingxing , Hu Weipeng , Zheng Feng
Published: November 2023

Introduction

The use of magnesium sulfate for treating aneurysmal subarachnoid hemorrhage (aSAH) has shown inconsistent results across studies. To assess the impact of magnesium sulfate on outcomes after aSAH, we conducted a systematic review and meta-analysis of relevant randomized controlled trials.

Methods

PubMed, Embase, and the Cochrane Library were searched for relevant literature on magnesium sulfate for aSAH from database inception to March 20, 2023. The primary outcome was cerebral vasospasm (CV), and secondary outcomes included delayed cerebral ischemia (DCI), secondary cerebral infarction, rebleeding, neurological dysfunction, and mortality.

Results

Of the 558 identified studies, 16 comprising 3,503 patients were eligible and included in the analysis. Compared with control groups (saline or standard treatment), significant differences were reported in outcomes of CV [odds ratio (OR) = 0.61, p = 0.04, 95% confidence interval (CI) (0.37–0.99)], DCI [OR = 0.57, p = 0.01, 95% CI (0.37–0.88)], secondary cerebral infarction [OR = 0.49, p = 0.01, 95% CI (0.27–0.87)] and neurological dysfunction [OR = 0.55, p = 0.04, 95% CI (0.32–0.96)] after magnesium sulfate administration, with no significant differences detected in mortality [OR = 0.92, p = 0.47, 95% CI (0.73–1.15)] and rebleeding [OR = 0.68, p = 0.55, 95% CI (0.19–2.40)] between the two groups.

Conclusion

The superiority of magnesium sulfate over standard treatments for CV, DCI, secondary cerebral infarction, and neurological dysfunction in patients with aSAH was demonstrated. Further randomized trials are warranted to validate these findings with increased sample sizes.
The epidemiology of traumatic brain injuries in the fastest-paced city in China: a retrospective study
Authors: Zou Jun-feng , Fang Hai-lan , Zheng Jing , Ma Yu-qiang , Wu Chu-wei , Su Gao-jian , Liu Xian-sheng , Liu Jun , Gao Jie , Zhang Jie-hua , Zhu Dong-liang , Shi Xin , Huang Xian-jian
Published: November 2023

Introduction

Traumatic brain injury (TBI) seriously affects the quality of human health and the prognosis of the patient, but the epidemiological characteristics of TBI can vary among populations. Numerous changes have occurred in the epidemiological characteristics of individuals with TBI in the fast-paced city of Shenzhen, China. However, little is known about these characteristics. This study aimed to investigate the changes in TBI epidemiology, help clinicians improve medical treatment.

Methods

In this retrospective cross-sectional analysis, we collected the data of 4,229 patients with TBI admitted to 20 hospitals in Shenzhen in 2017. We collected data on age, gender, cause and severity of the injury, eventual diagnosis, time from injury to admission in a neurosurgery department, and patient outcomes. Two neurosurgeons simultaneously collected the data. We compared these results with a similar study conducted in Shenzhen during the period from 1994 to 2003 to clarify and explain the changes in the epidemiological characteristics of TBI.

Results

The majority of respondents were men [2,830 (66.9%)]. The mean age was 32.5 ± 21.4 years. The youngest patient was less than 1 year old, and the oldest patient was 101 years old. A total of 3,947 (93.3%) patients had a favorable outcome, 219 (5.2%) had an unfavorable outcome, and 63 (1.5%) died. The predominant external cause was falls (1,779 [42.1%]); this was the most common cause of TBI in children and older adults. Riders of electric bicycles (423 [29.0%]) were the most vulnerable to traffic accident-related injuries. Time greater than 50 h from injury to admission to a neurosurgical department had a significant effect on prognosis (p < 0.001).

Conclusion

The epidemiological characteristics of TBI have changed significantly over the past 20 years. Falls, rather than traffic accidents, were the most common cause of TBI. Further research is needed to devise solutions to decrease the incidence of falls and improve the outcomes of TBI.
Can inertial measurement unit sensors evaluate foot kinematics in drop foot patients using functional electrical stimulation?
Authors: d'Andrea Francesca , Taylor Paul , Yang Kai , Heller Ben
Published: November 2023

The accuracy of inertial measurement units (IMUs) in measuring foot motion in the sagittal plane has been previously compared to motion capture systems for healthy and impaired participants. Studies analyzing the accuracy of IMUs in measuring foot motion in the frontal plane are lacking. Drop foot patients use functional electrical stimulation (FES) to improve walking and reduce the risk of tripping and falling by improving foot dorsiflexion and inversion-eversion. Therefore, this study aims to evaluate if IMUs can estimate foot angles in the frontal and sagittal planes to help understand the effects of FES on drop foot patients in clinical settings. Two Gait Up sensors were used to estimate foot dorsi-plantar flexion and inversion-eversion angles in 13 unimpaired participants and 9 participants affected by drop foot while walking 6 m in a straight line. Unimpaired participants were asked to walk normally at three self-selected speeds and to simulate drop foot. Impaired participants walked with and without FES assistance. Foot angles estimated by the IMUs were compared with those measured from a motion capture system using curve RMSE and Bland Altman limits of agreement. Between participant groups, overall errors of 7.95° ± 3.98°, −1.12° ± 4.20°, and 1.38° ± 5.05° were obtained for the dorsi-plantar flexion range of motion, dorsi-plantar flexion at heel strike, and inversion-eversion at heel strike, respectively. The between-system comparison of their ability to detect dorsi-plantar flexion and inversion-eversion differences associated with FES use on drop foot patients provided limits of agreement too large for IMUs to be able to accurately detect the changes in foot kinematics following FES intervention. To the best of the authors' knowledge, this is the first study to evaluate IMU accuracy in the estimation of foot inversion-eversion and analyze the potential of using IMUs in clinical settings to assess gait for drop foot patients and evaluate the effects of FES. From the results, it can be concluded that IMUs do not currently represent an alternative to motion capture to evaluate foot kinematics in drop foot patients using FES.
Age-induced nitrative stress decreases retrograde transport of proNGF via TrkA and increases proNGF retrograde transport and neurodegeneration via p75NTR
Authors: Kropf Erika , Shekari Arman , Jaberi Sama , Puri Anish , Wu Chengbiao , Fahnestock Margaret
Published: November 2023

Introduction

Axonal transport of pro nerve growth factor (proNGF) is impaired in aged basal forebrain cholinergic neurons (BFCNs), which is associated with their degeneration. ProNGF is neurotrophic in the presence of its receptor tropomyosin-related kinase A (TrkA) but induces apoptosis via the pan-neurotrophin receptor (p75NTR) when TrkA is absent. It is well established that TrkA is lost while p75NTR is maintained in aged BFCNs, but whether aging differentially affects transport of proNGF via each receptor is unknown. Nitrative stress increases during aging, but whether age-induced nitrative stress differentially affects proNGF transport via TrkA versus p75NTR has not yet been studied. Answering these questions is essential for developing an accurate understanding of the mechanisms contributing to age-induced loss of proNGF transport and BFCN degeneration.

Methods

In this study, fluorescence microscopy was used to analyze axonal transport of quantum dot labeled proNGF in rat BFCNs in vitro. Receptor specific effects were studied with proNGF mutants that selectively bind to either TrkA (proNGF-KKE) or p75NTR (proNGF-Δ9-13). Signaling factor activity was quantified via immunostaining.

Results

Young BFCNs transported proNGF-KKE but not proNGF-Δ9-13, and proNGF transport was not different in p75NTR knockout BFCNs compared to wildtype BFCNs. These results indicate that young BFCNs transport proNGF via TrkA. In vitro aging increased transport of proNGF-Δ9-13 but decreased transport of proNGF-KKE. Treatment with the nitric oxide synthase inhibitor L-NAME reduced retrograde transport of proNGF-Δ9-13 in aged BFCNs while increasing retrograde transport of proNGF-KKE but did not affect TrkA or p75NTR levels. ProNGF-Δ9-13 induced greater pro-apoptotic signaling and neurodegeneration and less pro-survival signaling relative to proNGF-KKE.

Discussion

Together, these results indicate that age-induced nitrative stress decreases proNGF transport via TrkA while increasing proNGF transport via p75NTR. These transport deficits are associated with decreased survival signaling, increased apoptotic signaling, and neurodegeneration. Our findings elucidate the receptor specificity of age-and nitrative stress-induced proNGF transport deficits. These results may help to rescue the neurotrophic signaling of proNGF in aging to reduce age-induced loss of BFCN function and cognitive decline.
Assessment of the temporal trend and daily profiles of the dietary purine intake among Chinese residents during 2014 to 2021
Authors: Li Shiwen , Liu Xin , Jia Xiwu , Fang Min , Yang Qing , Gong Zhiyong
Published: November 2023

The incidence of hyperuricemia is on the rise in China, primarily due to dietary habits. However, limited data exists regarding dietary purine intake in the country. This study aimed to estimate the daily dietary purine intake among Chinese residents from 2014 to 2021 and evaluate the temporal trend using joinpoint regression analysis. The analysis revealed an annual percentage change (APC) of 0.8% (95% CI: 0.1–1.5%) in dietary purine intake prior to the joinpoint (2014–2019). Following the joinpoint (2019–2021), the APC significantly increased to 6.5% (95% CI: 3.3–9.8%), indicating a noteworthy upward trend (p = 0.045). Furthermore, the average daily purine intake varied significantly among different regions of China, with the southern region showing the highest dietary intake of purines. Considering the diverse contributions of various food sources to dietary purine intake, it was observed that meat consumption had the greatest impact, accounting for 36.2% of purine intake, followed by cereals consumption (25.3%) and vegetables and edible fungi (24.2%). These findings hold significance for dietary intervention and management strategies aimed at reducing purine intake among the population.
An improved multi-scale gradient generative adversarial network for enhancing classification of colorectal cancer histological images
Authors: Jiang Liwen , Huang Shuting , Luo Chaofan , Zhang Jiangyu , Chen Wenjing , Liu Zhenyu
Published: November 2023

Introduction

Deep learning-based solutions for histological image classification have gained attention in recent years due to their potential for objective evaluation of histological images. However, these methods often require a large number of expert annotations, which are both time-consuming and labor-intensive to obtain. Several scholars have proposed generative models to augment labeled data, but these often result in label uncertainty due to incomplete learning of the data distribution.

Methods

To alleviate these issues, a method called InceptionV3-SMSG-GAN has been proposed to enhance classification performance by generating high-quality images. Specifically, images synthesized by Multi-Scale Gradients Generative Adversarial Network (MSG-GAN) are selectively added to the training set through a selection mechanism utilizing a trained model to choose generated images with higher class probabilities. The selection mechanism filters the synthetic images that contain ambiguous category information, thus alleviating label uncertainty.

Results

Experimental results show that compared with the baseline method which uses InceptionV3, the proposed method can significantly improve the performance of pathological image classification from 86.87% to 89.54% for overall accuracy. Additionally, the quality of generated images is evaluated quantitatively using various commonly used evaluation metrics.

Discussion

The proposed InceptionV3-SMSG-GAN method exhibited good classification ability, where histological image could be divided into nine categories. Future work could focus on further refining the image generation and selection processes to optimize classification performance.
Case Report: A novel TP53 mutation in a patient with quadruple wild-type gastrointestinal stromal tumor
Authors: Chen Yuhong , Chen Junyong , Long Liansheng , Han Leng , Mi Xiaohui , Song Yanfang , Cheng Huanqing , Zhang Yanrui , Cheng Liyang
Published: November 2023

In this report, we present a case study of a 64-year-old female who was diagnosed with gastrointestinal stromal tumors (GISTs) and subsequently developed liver metastases despite undergoing radical resection. Next-generation sequencing (NGS) assays indicated that the tumor lacked KIT/PDGFRA/SDH/RAS-P (RAS pathways, RAS-P) mutations, thereby classifying this patient as quadruple WT GIST (qGIST). Treatment with imatinib was initiated, and after 2.5 months, recurrence of the tumor and multiple metastases around the surgical site were observed. Consequently, the patient was switched to sunitinib treatment and responded well. Although she responded well to sunitinib, the patient died of tumor dissemination within 4 months. This case study highlights the potential efficacy of imatinib and the VEGFR-TKI sunitinib in treating qGIST patients harboring a TP53 missense mutation.
Extracellular vesicle small RNA cargo discriminates non-cancer donors from pediatric B-lymphoblastic leukemia patients
Authors: Longjohn Modeline N. , Hudson Jo-Anna B. J. , Peña-Castillo Lourdes , Cormier Robert P. J. , Hannay Brandon , Chacko Simi , Lewis Stephen M. , Moorehead Paul C. , Christian Sherri L.
Published: November 2023

Pediatric B-acute lymphoblastic leukemia (B-ALL) is a disease of abnormally growing B lymphoblasts. Here we hypothesized that extracellular vesicles (EVs), which are nanosized particles released by all cells (including cancer cells), could be used to monitor B-ALL severity and progression by sampling plasma instead of bone marrow. EVs are especially attractive as they are present throughout the circulation regardless of the location of the originating cell. First, we used nanoparticle tracking analysis to compare EVs between non-cancer donor (NCD) and B-ALL blood plasma; we found that B-ALL plasma contains more EVs than NCD plasma. We then isolated EVs from NCD and pediatric B-ALL peripheral blood plasma using a synthetic peptide-based isolation technique (Vn96), which is clinically amenable and isolates a broad spectrum of EVs. RNA-seq analysis of small RNAs contained within the isolated EVs revealed a signature of differentially packaged and exclusively packaged RNAs that distinguish NCD from B-ALL. The plasma EVs contain a heterogenous mixture of miRNAs and fragments of long non-coding RNA (lncRNA) and messenger RNA (mRNA). Transcripts packaged in B-ALL EVs include those involved in negative cell cycle regulation, potentially suggesting that B-ALL cells may use EVs to discard gene sequences that control growth. In contrast, NCD EVs carry sequences representative of multiple organs, including brain, muscle, and epithelial cells. This signature could potentially be used to monitor B-ALL disease burden in pediatric B-ALL patients via blood draws instead of invasive bone marrow aspirates.
Dosimetric comparison in sparing normal tissue dosage by using auto-SBRT planning in oligo liver tumors
Authors: Zhang Shu , Zhan Weiyi , Zeng Ni , Yang Jiangping , Xiong Maoqi , Liao Wenjun , Chen Nianyong , Xiao Jianghong
Published: November 2023

Purpose

The study aimed to compare the dosimetric distribution of VMAT plans by increasing the number of half arcs in liver SBRT and investigate the effect by using automatic plan software in plan optimization.

Method

Thirty-one patients with oligo liver tumors were randomly selected. VMAT treatment plans with different numbers of coplanar half arcs were generated.

Result

Adding arcs significantly increased the PTV, D2%, D50%, and CI, but sacrificed the plan homogeneity. It also decreased the maximum dose of normal tissues such as the stomach, duodenum, and spinal cord and reduced Dmean, D500cc, and D700cc for the liver. Nevertheless, the diminishing effect gradually decayed into three arcs. Meanwhile, the addition of arcs substantially extended the beam-on time.

Conclusion

In the context of SBRT for oligo liver tumors, increasing the number of coplanar half arcs will improve PTV conformity and offer better protection for OARs, albeit at the expense of increased treatment duration. Considering the trade-off between plan quality and treatment efficiency, a three-arc plan may be more suitable for clinical implementation.
Grand challenges in organizational justice, diversity and equity
Authors: Konrad Alison M. , Bhardwaj Arjun
Published: November 2023

This inaugural article founding the Frontiers Journal Section on Organizational Justice, Diversity and Equity highlights four broad areas requiring further research in our field. First, organizational justice and DEI share common threads, and there is considerable room for work that conceptually integrates these two areas of study. Specifically, we need research that helps us understand how organizations as inequality-producing systems create and maintain perceptions of (un)fairness when individuals receive unequal rewards for their contributions, particularly in diverse workplaces. Furthermore, research is needed to enhance understanding of how to create and maintain high levels of organizational justice for both marginalized and predominant identity groups. Additionally, this is a space for empirical work that replicates prior findings, something that is essential to the development of science. It is also important to expand the scope of justice and DEI scholarship with a greater inclusion of research contexts from the Global South. Finally, Organizational Justice and DEI topics are inflamed in the contemporary U.S. context, and there is a need for investigation of how the societal context influences the development of our field.
Anti-PD-1/PD-L1 for nasopharyngeal carcinoma: a comprehensive analysis of registered trials on ClinicalTrials.gov
Authors: Dai Zelei , Li Nian , Wang Jun , Tan Chenfeng , Zhang Yonggang , Liu Lei
Published: November 2023

Objective: Clinical trials play an important role in the development of healthcare. However, the current status of clinical trials on anti-PD-1/PD-L1 for nasopharyngeal carcinoma remains unclear. Therefore, this study aims to provide a comprehensive analysis of the registered trials related to anti-PD-1/PD-L1 for nasopharyngeal carcinoma on ClinicalTrials.gov.

Methods: A search was conducted on the ClinicalTrials.gov database to identify all registered trials related to anti-PD-1/PD-L1 for nasopharyngeal carcinoma up to 26 February 2023. The characteristics of the trials were examined, and the studied drugs, disease conditions, as well as details of trials with available results were analyzed. Publication status was assessed by a PubMed search using the ClinicalTrials.gov NCT number.

Results: A total of 112 interventional clinical trials registered between 2015 and 2023 were included. Of the trials, 90 were carried out in Asia, 72 were in phase 2, and 31 trials had either companies or universities as sponsors/collaborators. The sample sizes across the trials varied greatly, with a median of 71.5 participants per trial. The majority of trials were recruiting participants, with only 6 had posted results. PD-1 inhibitors were preferred over PD-L1, and Toripalimab emerged as the most extensively studied drug. About one-third (33.9%) of the studies looked into recurrent/metastatic nasopharyngeal cancer.

Conclusion: This study provides an overview of all registered trials of anti-PD-1/PD-L1 for NPC. It is needed to improve the completeness, outcome selection, randomization and masking of trials and to be transparent and timely in reporting of results.
Synergistic effect of Euphorbia kansui stir-fried with vinegar and bile acids on malignant ascites effusion through modulation of gut microbiota
Authors: Dai Shengyun , Zhou Shikang , Ju Yonghui , Yao Weifeng , Tang Yuping , Zheng Jian , Ma Shuangcheng , Zhang Yi , Zhang Li
Published: November 2023

Background: Toxic Euphorbia kansui (EK) is employed to treat malignant ascites effusion (MAE). EK stir-fried with vinegar (VEK) has been demonstrated to reduce toxicity due to its preserved water-expelling effect. This was demonstrated to be correlated with gut microbiota. Therein, bile acids (BAs) have a bidirectional relationship with the gut microbiota. Therefore, the aim of this study is to explore whether BA-mediated gut microbiota influences the water-expelling effect of VEK against MAE.

Methods: The MAE rat model was established by intraperitoneal injection of Walker-256 tumor cells. A reliable simultaneous method for the determination of 15 bile acids in rat feces using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established and applied to analyze the fecal BAs in rats treated with VEK. The screened BA was then administered to VEK-treated MAE rats. The water-expelling effect was evaluated using histopathological analysis, biochemical examination, inflammatory factors in ascites, urine volume, ascites amount, and intestinal aquaporin expression. The microbial composition was determined using 16S rRNA sequencing, and the contents of bile acids were finally measured.

Results: VEK decreased the content of fecal deoxycholic acid (DCA), lithocholic acid (LCA), and taurocholic acid (TCA) while increasing the content of ursodeoxycholic acid (UDCA). VEK alleviated liver, stomach, and intestinal injuries; oxidative damage; and inflammation, which were further ameliorated with UDCA intervention. VEK alleviated MAE by increasing the fecal water content, urine volume, and AQP3 protein expression and decreasing the urine levels of Na+, K+, and Cl−. This was retained with the intervention of UDCA. UDCA and VEK regulated the BA metabolism disorder to a certain extent. Analysis of gut microbiota showed that VEK increased the abundance of Lactobacillus and decreased that of Prevotella_9 in MAE rats. The combined administration of UDCA and VEK showed a better modulation of the microbiota structure than that of VEK alone, and the effect of this administration reached closer to the reference state.

Conclusion: The water-expelling effect of VEK did not directly depend on the BA-mediated gut microbiota. However, VEK and BAs had a synergistic effect on malignant ascites effusion through the regulation of the gut microbiota. These results provided a scientific basis for the reasonable usage of VEK and the novel combination treatment strategy of VEK and UDCA.