bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and biomarker analyses of hepatic arterial infusion chemotherapy plus lenvatinib and PD-1 inhibitor for patients with advanced intrahepatic cholangiocarcinoma
Authors: Huang YeXing , Du ZeFeng , Kan Anna , He MinKe , Li HuiFang , Lai ZhiCheng , Wen DongSheng , Huang LiChang , Li QiJiong , Xu Li , Shi Ming
Published: February 2024

Background

Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive cancer with a dismal prognosis and few effective therapeutic approaches. This study aimed to investigate the efficacy, safety, and predictive biomarkers of hepatic arterial infusion chemotherapy (FOLFOX-HAIC) in combination with lenvatinib and PD-1 inhibitor for patients with advanced iCCA.

Methods

Locally advanced or metastatic iCCA patients receiving the triple combination therapy of lenvatinib, PD-1 inhibitor, and FOLFOX-HAIC were included in this retrospective study. Primary endpoint was the progression-free survival, evaluated using the RECIST criterion. The secondary endpoints included overall survival, objective response rate, and safety. Whole exome and RNA sequencing of tumor biopsy tissues were performed for biomarker exploration.

Results

Between May, 2019 and December 2022, a total of 46 patients were included in this study. The primary endpoint showed a median progression-free survival of 9.40 months (95% CI: 5.28-13.52), with a 6-month progression-free survival rate of 76.1%. The median overall survival was 16.77 months (95% CI, 14.20-19.33), with an objective response rate of 47.8% and disease control rate of 91.3% per RECIST. In addition, 4.3% and 8.7% of patients achieved complete response of all lesions and intrahepatic target lesions per mRECIST, respectively. The most common treatment-related adverse events were neutropenia, thrombocytopenia, elevated aspartate aminotransferase and alanine aminotransferase level. Furthermore, integrated analysis of genetic, transcriptomic, and immunohistochemistry data revealed that pre-existing immunity (high expression level of immune-related signatures and intra-tumoral CD8+ T cell density) in baseline tumor tissues was associated with superior clinical benefits. However, the evaluation of tumor mutation burden did not show potential predictive value in this triple combination.

Conclusion

FOLFOX-HAIC in combination with lenvatinib and PD-1 inhibitor demonstrated a promising antitumor activity with manageable safety profiles in patients with advanced iCCA. Moreover, our study also revealed new perspectives on potential biomarkers for clinical efficacy.
Adoptive cell therapy for high grade gliomas using simultaneous temozolomide and intracranial mgmt-modified γδ t cells following standard post-resection chemotherapy and radiotherapy: current strategy and future directions
Authors: Nabors L. B. , Lamb L. S. , Goswami T. , Rochlin K. , Youngblood S. L.
Published: February 2024

Cellular therapies, including chimeric antigen receptor T cell therapies (CAR-T), while generally successful in hematologic malignancies, face substantial challenges against solid tumors such as glioblastoma (GBM) due to rapid growth, antigen heterogeneity, and inadequate depth of response to cytoreductive and immune therapies, We have previously shown that GBM constitutively express stress associated NKG2D ligands (NKG2DL) recognized by gamma delta (γδ) T cells, a minor lymphocyte subset that innately recognize target molecules via the γδ T cell receptor (TCR), NKG2D, and multiple other mechanisms. Given that NKG2DL expression is often insufficient on GBM cells to elicit a meaningful response to γδ T cell immunotherapy, we then demonstrated that NKG2DL expression can be transiently upregulated by activation of the DNA damage response (DDR) pathway using alkylating agents such as Temozolomide (TMZ). TMZ, however, is also toxic to γδ T cells. Using a p140K/MGMT lentivector, which confers resistance to TMZ by expression of O(6)-methylguanine-DNA-methyltransferase (MGMT), we genetically engineered γδ T cells that maintain full effector function in the presence of therapeutic doses of TMZ. We then validated a therapeutic system that we termed Drug Resistance Immunotherapy (DRI) that combines a standard regimen of TMZ concomitantly with simultaneous intracranial infusion of TMZ-resistant γδ T cells in a first-in-human Phase I clinical trial (NCT04165941). This manuscript will discuss DRI as a rational therapeutic approach to newly diagnosed GBM and the importance of repeated administration of DRI in combination with the standard-of-care Stupp regimen in patients with stable minimal residual disease.
Global research trends on innate lymphoid cells in the brain, gut and lung field: a bibliometric and visualized analysis
Authors: Huang Jianliang , Deng Kun , Liu Ying , Xia Mingkai , Lei Mingsheng , Wu Minghua
Published: February 2024

Background

ILCs play important roles in the brain, gut, and lungs. Researchers are attempting to establish a research framework on the brain-gut-lung axis using ILCs. However, no one has yet conducted a bibliometric analysis to summarize the findings. In this study, we utilized bibliometrics to analyze the emerging trends and focal areas of ILCs in the brain, intestine, and lung. We aim to provide references for future research on the brain-gut-lung axis.

Methods

To conduct a comprehensive bibliometric analysis on ILCs in the fields of brain, intestine, and lung, we utilized software such as HistCite, VOSviewer, and CiteSpace. Our analysis focused on various aspects, including the number of publications, countries, authors, journals, co-cited documents, and keywords. This approach allowed us to gain valuable insights into the research landscape surrounding ILCs in these specific fields.

Results

A total of 8411 articles or reviews on ILCs in the fields of brain, intestine, and lung were included. The number of published articles has shown a consistent upward trend since 2003. A total of 45279 authors from 99 countries have contributed to these articles. The United States has the highest number of publications (n=3044) and the most cited articles (TGCS=210776). The top three published authors in this field are David Artis, Marco Colonna and Andrew NJ McKenzie. The journal Immunity is the most authoritative choice for researchers. The main research focuses in this field include NK cell, ILC2, tumor immunity, multiple sclerosis, inflammatory bowel disease, airway inflammation, RORγT, and immunotherapy. In recent years, cancer and tumor microenvironment have emerged as hot keywords, particularly immunotherapy, PD-1 related directions, indicating a potential shift in research focus.

Conclusion

European and American countries have been pivotal in conducting research on ILCs, while China has produced a significant number of publications, its impact is still limited. Tumors are likely to emerge as the next focal points in this field. The connection and regulation between the brain and the lung are not yet fully understood, and further investigation is necessary to explore the role of ILCs in the brain-lung axis.
Fc receptors are key discriminatory markers of granulocytes subsets in people living with HIV-1
Authors: Marsile-Medun Soledad , Souchard Manon , Abba Moussa Daouda , Reynaud Élisa , Tuaillon Edouard , Naranjo-Gomez Mar , Pelegrin Mireia
Published: February 2024

Introduction

Granulocytes are innate immune cells that play a key role in pathogen elimination. Recent studies revealed the diversity of granulocytes in terms of phenotype and function. In particular, a subset of granulocytes identified as low-density granulocytes (LDG) has been described in physiological conditions and with increased frequencies in several pathological contexts. However, the properties of LDG are still controversial as they vary according to the pathophysiological environment. Here we investigated the heterogeneity of granulocyte populations and the potential differences in phenotype and immunomodulatory capacity between LDG and normal density granulocytes (NDG) in people living with HIV-1 (PLWH).

Methods

To this end, we developed an optimized method to purify LDG and NDG from a single blood sample, and performed in-depth, comparative phenotypic characterization of both granulocyte subtypes. We also assessed the impact of purification steps on the expression of cell surface markers on LDG by immunophenotyping them at different stages of isolation.

Results

We identified 9 cell surface markers (CD16, CD32, CD89, CD62L, CD177, CD31, CD10, CXCR4 and CD172α) differentially expressed between LDG and NDG. Noteworthy, markers that distinguish the two subsets include receptors for the Fc part of IgG (CD16, CD32) and IgA (CD89). Importantly, we also highlighted that the purification procedure affects the expression of several cell surface markers (i.e.CD63, CD66b, …) which must be taken into account when characterizing LDG. Our work sheds new light on the properties of LDG in PLWH and provides an extensive characterization of this granulocyte subset in which Fc receptors are key discriminatory markers.
IFNs in host defence and parasite immune evasion during Toxoplasma gondii infections
Authors: Lüder Carsten G. K.
Published: February 2024

Interferons (IFNs) are a family of cytokines with diverse functions in host resistance to pathogens and in immune regulation. Type II IFN, i.e. IFN-γ, is widely recognized as a major mediator of resistance to intracellular pathogens, including the protozoan Toxoplasma gondii. More recently, IFN-α/β, i.e. type I IFNs, and IFN-λ (type III IFN) have been identified to also play important roles during T. gondii infections. This parasite is a widespread pathogen of humans and animals, and it is a model organism to study cell-mediated immune responses to intracellular infection. Its success depends, among other factors, on the ability to counteract the IFN system, both at the level of IFN-mediated gene expression and at the level of IFN-regulated effector molecules. Here, I review recent advances in our understanding of the molecular mechanisms underlying IFN-mediated host resistance and immune regulation during T. gondii infections. I also discuss those mechanisms that T. gondii has evolved to efficiently evade IFN-mediated immunity. Knowledge of these fascinating host-parasite interactions and their underlying signalling machineries is crucial for a deeper understanding of the pathogenesis of toxoplasmosis, and it might also identify potential targets of parasite-directed or host-directed supportive therapies to combat the parasite more effectively.
POIs-based public preferences mapping on imbalanced supply-demand of recreation services can support sustainable coastal beach management
Authors: Li Tong , Xiang Zhiyuan , Li Yangfan
Published: February 2024

Cultural ecosystem services (CES) based on nature experiences substantially contribute to public health and human well-being. However, CES’s supply-demand methodology remains scarcely explored on the coastal beach, and the demand relating to public preferences has not been sufficiently unveiled in spatial assessment. Here, we selected recreation services as a lens of CES and applied the knowledge of multi-source big data to better reflect public preferences. Point of Interests (POIs) refer to particularly valuable or interesting places. We proposed to integrate POIs and social media data (Weibo check-in) to quantify the demand for beach recreation services (BRS). We also used socio-ecological indicators to quantify the BRS’s supply. The supply-demand balance of BRS was further identified by quadrant analysis and coupling coordination degree. Our methodology was applied to a typical coastal zone, Shenzhen Dapeng New District, in the Greater Bay Area of China. Over 80% of the beaches in the study area exhibited an imbalanced or barely balanced supply-demand of recreation services. We found that POIs density had a significant influence on a balanced supply-demand of BRS. Multi-source big data (POIs and Weibo check-in) provided an efficient, low-cost, and across-scale approach for public preference mapping than traditional questionnaire surveys. The proposed CES’s supply-demand framework can identify coastal beaches with imbalanced recreation and support sustainable coastal management. Coastal beach management prioritizes not only waste prevention and sufficient safety signs but also proper infrastructure development that contribute sustainably to the human well-being of nature experiences.
The experience of good mentoring focused on overcoming turnover intention among millennial nurses
Authors: Jung Seo-Yeon , Kim Jung-Hee
Published: February 2024

Introduction

Millennials are emerging as a prominent demographic in the nursing workforce. It is necessary to create an environment that harmonizes the advantages of each generation in a nursing workforce in which various generations coexist. As the importance of mentoring programs for millennial nurses grows, it is believed that the effectiveness of mentoring to support millennial nurses can be enhanced by identifying the attributes of good mentors as perceived by nurses. This study aimed to explore the attributes of good mentors according to millennial nurses in the nursing workforce with a focus on overcoming turnover intention problems.

Methods

Four focus group interviews were conducted to collect data, which were subsequently analyzed using Braun and Clarke’s thematic analysis method. A descriptive qualitative design involving 22 millennial nurses employed at a tertiary hospital, Hospital A, in Seoul, Republic of Korea was utilized.

Results and discussion

Four themes emerged from the analysis: the concept of a significant others, the presence of a driving force to endure, the importance of a guide to a harmonious life, and the value of a partner for growth. The participants themselves identified these themes. To prevent turnover intention among millennial nurses, mentors should employ diverse strategies, and institutional supports are crucial. Furthermore, since it is unrealistic to expect all ideal mentor characteristics to be present in one person, mentor development education is also necessary. This information is valuable for designing mentor development programs and for establishing a solid framework for effective mentoring programs.
Risk factors for progression of pulmonary fibrosis: a single-centered, retrospective study
Authors: Fan Jia-Jia , Gu Jin-Min , Xiao Si-Yao , Jia Ming-Yue , Han Gui-Ling
Published: February 2024

Objective

This study aimed to identify clinical characteristics associated with the prevalence of progressive pulmonary fibrosis (PPF) in interstitial lung disease (ILD) and to develop a prognostic nomogram model for clinical use.

Methods

In this single-centered, retrospective study, we enrolled ILD patients with relatively comprehensive clinical data and assessed the incidence of PPF within a year using collected demographics, laboratory data, high-resolution computed tomography (HRCT), and pulmonary function test (PFT) results. We used a training cohort of ILD patients to identify early predictors of PPF and then validated them in an internal validation cohort and subsets of ILD patients using a multivariable logistic regression analysis. A prognostic nomogram was formulated based on these predictors, and the accuracy and efficiency were evaluated using the area under the receiver operating characteristic curve (AUC), calibration plot, and decision curve analysis (DCA).

Results

Among the enrolled patients, 120 (39.09%) cases had connective tissue disease-associated interstitial lung disease (CTD-ILD), 115 (37.46%) had non-idiopathic pulmonary fibrosis idiopathic interstitial pneumonia (non-IPF IIP), and 35 (11.4%) had hypersensitivity pneumonitis (HP). Overall, 118 (38.4%) cases experienced pulmonary fibrosis progression. We found that baseline DLco% pred (OR 0.92; 95% CI, 8.93–0.95) was a protective factor for ILD progression, whereas combined pneumonia (OR 4.57; 95% CI, 1.24–18.43), modified Medical Research Council dyspnea score (mMRC) (OR 4.9; 95% CI, 2.8–9.5), and high-resolution computed tomography (HRCT) score (OR 1.22; 95% CI, 1.07–1.42) were independent risk factors for PPF. The AUC of the proposed nomogram in the development cohort was 0.96 (95% CI, 0.94, 0.98), and the calibration plot showed good agreement between the predicted and observed incidence of PPF (Hosmer–Lemeshow test: P = 0.86).

Conclusion

ILD patients with combined pneumonia, low baseline DLco% pred, high mMRC marks, and high HRCT scores were at higher risk of progression. This nomogram demonstrated good discrimination and calibration, indicating its potential utility for clinical practice.
The systemic immune-inflammation index is significantly associated with the severity of silicosis: a 9-year retrospective study in Beijing
Authors: Kang Han-Yu-Jie , Cao Si-Yu , Shao Shuai , Liang Li-Rong , Tong Zhao-Hui
Published: February 2024

Background

Silicosis shows an increasing trend with the development of new industries. However, the potential biomarkers for predicting the disease severity are lacking. A novel inflammatory marker, the systemic immune-inflammation Index (SII), has not been studied in silicosis.

Methods

In this retrospective study, we used data from a big database platform of a tertiary general hospital in Beijing, which was established based on the electronic medical records of the hospital. The clinical data of adult patients diagnosed with silicosis at the Department of Occupational Medicine and Toxicology from 2013 to 2022 were collected. The data extracted from the database were in de-identified form. Only patients with a first diagnosis of silicosis and without conditions that might affect the parameters of routine blood tests were included in the analysis. Analyses were performed to assess the relationship between SII and the advanced stage of silicosis.

Results

A total of 246 participants were included in the study. Most of the patients were exposed to silica particles during excavation and digging (n = 149, 60.6%). SII level was significantly higher in patients with advanced stages of silicosis. A multivariate logistic regression analysis revealed that a higher SII level was associated with the advanced stage of silicosis [odds ratio (OR) = 1.002; 95% confidence interval (CI): 1.000–1.003, p < 0.001] after adjusting for all covariates. The best cutoff value of SII was 444.1. The results of the subgroup analysis also showed a significant correlation between SII level over 444.1 and the advanced stage of silicosis in groups stratified by gender, history of smoking, and duration of silica exposure. Moreover, our results showed a significant but weak negative correlation between the level of SII and some lung function parameters in silicosis.

Conclusion

Higher SII is associated with the advanced stage of silicosis and impaired lung function. More long-term, large-scale studies are needed to confirm these findings.
No evidence for a causal link between Helicobacter pylori infection and Irritable bowel syndrome: a Mendelian randomization study
Authors: Wang Chenchen , Zhang Jing , Han Fengli , Liu Dong , Han Yuying
Published: February 2024

Background

Although clinical studies have revealed a potential link between Helicobacter pylori (H. pylori) infection and irritable bowel syndrome (IBS), the causal relationship between them remains unknown. The objective of this study was to investigate whether H. pylori infection is causally associated with IBS.

Method

A two-sample Mendelian randomization (MR) analysis using the inverse variance weighted (IVW), weighted mode, weighted median and MR-Egger methods was performed. We used the publicly available summary statistics data sets of genome-wide association studies (GWAS) for H. pylori infection in individuals of European descent (case = 1,058, control = 3,625) as the exposure and a GWAS for non-cancer illness code self-reported: IBS (case = 10,939, control = 451,994) as the outcome.

Results

We selected 10 single nucleotide polymorphisms at genome-wide significance from GWASs on H. pylori infection as the instrumental variables. The IVW, weighted mode, weighted median and MR-Egger methods all provided consistent evidence that suggests a lack of causal association between H. pylori and IBS. MR-Egger regression revealed that directional pleiotropy was unlikely to be biasing the result (intercept = −1e-04; P = 0.831). Cochran’s Q-test and the funnel plot indicated no evidence of heterogeneity and asymmetry, indicating no directional pleiotropy.

Conclusion

The results of MR analysis support that H. pylori infection may not be causally associated with an increased risk of IBS.
Bacterial cytochrome P450s: a bioinformatics odyssey of substrate discovery
Authors: Schottlender Gustavo , Prieto Juan Manuel , Clemente Camila , Schuster Claudio David , Dumas Victoria , Fernández Do Porto Darío , Martí Marcelo Adrian
Published: February 2024

Bacterial P450 cytochromes (BacCYPs) are versatile heme-containing proteins responsible for oxidation reactions on a wide range of substrates, contributing to the production of valuable natural products with limitless biotechnological potential. While the sequencing of microbial genomes has provided a wealth of BacCYP sequences, functional characterization lags behind, hindering our understanding of their roles. This study employs a comprehensive approach to predict BacCYP substrate specificity, bridging the gap between sequence and function. We employed an integrated approach combining sequence and functional data analysis, genomic context exploration, 3D structural modeling with molecular docking, and phylogenetic clustering. The research begins with an in-depth analysis of BacCYP sequence diversity and structural characteristics, revealing conserved motifs and recurrent residues in the active site. Phylogenetic analysis identifies distinct groups within the BacCYP family based on sequence similarity. However, our study reveals that sequence alone does not consistently predict substrate specificity, necessitating additional perspectives. The study delves into the genetic context of BacCYPs, utilizing neighboring gene information to infer potential substrates, a method proven very effective in many cases. Molecular docking is employed to assess BacCYP-substrate interactions, confirming potential substrates and providing insights into selectivity. Finally, a comprehensive strategy is proposed for predicting BacCYP substrates, involving all the evaluated approaches. The effectiveness of this strategy is demonstrated with two case studies, highlighting its potential for substrate discovery.
Urogenital microbiota-driven virulence factor genes associated with recurrent urinary tract infection
Authors: Jiang Lei , Wang Haiyun , Luo Lei , Pang Xiangyu , Liu Tongpeng , Sun Lijiang , Zhang Guiming
Published: February 2024

Urinary tract infections (UTIs) are a common health issue affecting individuals worldwide. Recurrent urinary tract infections (rUTI) pose a significant clinical challenge, with limited understanding of the underlying mechanisms. Recent research suggests that the urobiome, the microbial community residing in the urinary tract, may play a crucial role in the development and recurrence of urinary tract infections. However, the specific virulence factor genes (VFGs) driven by urobiome contributing to infection recurrence remain poorly understood. Our study aimed to investigate the relationship between urobiome driven VFGs and recurrent urinary tract infections. By analyzing the VFGs composition of the urinary microbiome in patients with rUTI compared to a control group, we found higher alpha diversity in rUTI patients compared with healthy control. And then, we sought to identify specific VFGs features associated with infection recurrence. Specifically, we observed an increased abundance of certain VGFs in the recurrent infection group. We also associated VFGs and clinical data. We then developed a diagnostic model based on the levels of these VFGs using random forest and support vector machine analysis to distinguish healthy control and rUIT, rUTI relapse and rUTI remission. The diagnostic accuracy of the model was assessed using receiver operating characteristic curve analysis, and the area under the ROC curve were 0.83 and 0.75. These findings provide valuable insights into the complex interplay between the VFGs of urobiome and recurrent urinary tract infections, highlighting potential targets for therapeutic interventions to prevent infection recurrence.
Unveiling the significance of TREM1/2 in hemorrhagic stroke: structure, function, and therapeutic implications
Authors: Kong Yancheng , Wang Di , Jin Xu , Liu Yi , Xu Hui
Published: February 2024

Stroke has long been a major threat to human health worldwide. Hemorrhagic stroke, including intracerebral hemorrhage and subarachnoid hemorrhage, exhibits a high incidence rate and a high mortality and disability rate, imposing a substantial burden on both public health and the economy and society. In recent years, the triggering receptor expressed on myeloid cells (TREM) family has garnered extensive attention in various pathological conditions, including hemorrhagic stroke. This review comprehensively summarizes the structure and function of TREM1/2, as well as their roles and potential mechanisms in hemorrhagic stroke, with the aim of providing guidance for the development of targeted therapeutic strategies in the future.
Traumatic tension pneumocephalus: a case report and perspective from Indonesia
Authors: Harlyjoy Alphadenti , Nathaniel Michael , Nugroho Aryandhito Widhi , Gunawan Kevin
Published: February 2024

Traumatic tension pneumocephalus is a rare and life-threatening complication of traumatic brain injury necessitating prompt diagnosis and neurosurgical treatment. Nevertheless, various possibilities for impedance in timely management, including patient-related barriers are commonly experienced in low-and middle-income countries setting. Here we presented a delay of management in traumatic tension pneumocephalus case due to initial refusal for emergency surgery. A 59-year-old male presented to the emergency department following a motorcycle accident fully alert with no neurological deficit. He acknowledged clear nasal discharge within 1 h after the initial trauma, but no rhinorrhea or otorrhea was present during physical examination. Head CT revealed extensive pneumocephalus with “Mount Fuji sign,” anterior skull base fracture, and frontal sinus fracture. The patient initially refused immediate surgical intervention due to excellent clinical condition and financial scare. Acute decrease of consciousness occurred 40 h post-trauma: GCS of 6 with slight dilatation of both pupils (4 mm) and sluggish pupillary reflex. Emergency bifrontal craniotomy, subdural air drainage, and dura mater tear repair were performed afterwards. Postoperative care was uneventful, with rapid improvement of consciousness and follow-up head CT showing minimal subdural fluid collection and absence of remaining pneumocephalus. The patient was discharged from the hospital after 7 days with GCS of 15 and GOS of 5, proving the importance of overcoming barriers for delay in delivering neurotrauma care in low-and middle-income countries.
Computational pathology-based weakly supervised prediction model for MGMT promoter methylation status in glioblastoma
Authors: He Yongqi , Duan Ling , Dong Gehong , Chen Feng , Li Wenbin
Published: February 2024

Introduction

The methylation status of oxygen 6-methylguanine-DNA methyltransferase (MGMT) is closely related to the treatment and prognosis of glioblastoma. However, there are currently some challenges in detecting the methylation status of MGMT promoters. The hematoxylin and eosin (H&E)-stained histopathological slides have always been the gold standard for tumor diagnosis.

Methods

In this study, based on the TCGA database and H&E-stained Whole slide images (WSI) of Beijing Tiantan Hospital, we constructed a weakly supervised prediction model of MGMT promoter methylation status in glioblastoma by using two Transformer structure models.

Results

The accuracy scores of this model in the TCGA dataset and our independent dataset were 0.79 (AUC = 0.86) and 0.76 (AUC = 0.83), respectively.

Conclusion

The model demonstrates effective prediction of MGMT promoter methylation status in glioblastoma and exhibits some degree of generalization capability. At the same time, our study also shows that adding Patches automatic screening module to the computational pathology research framework of glioma can significantly improve the model effect.
Oscillatory activity underlying cognitive performance in children and adolescents with autism: a systematic review
Authors: Soto-Icaza Patricia , Soto-Fernández Patricio , Kausel Leonie , Márquez-Rodríguez Víctor , Carvajal-Paredes Patricio , Martínez-Molina María Paz , Figueroa-Vargas Alejandra , Billeke Pablo
Published: February 2024

Autism spectrum disorder (ASD) is a neurodevelopmental condition that exhibits a widely heterogeneous range of social and cognitive symptoms. This feature has challenged a broad comprehension of this neurodevelopmental disorder and therapeutic efforts to address its difficulties. Current therapeutic strategies have focused primarily on treating behavioral symptoms rather than on brain psychophysiology. During the past years, the emergence of non-invasive brain stimulation techniques (NIBS) has opened alternatives to the design of potential combined treatments focused on the neurophysiopathology of neuropsychiatric disorders like ASD. Such interventions require identifying the key brain mechanisms underlying the symptomatology and cognitive features. Evidence has shown alterations in oscillatory features of the neural ensembles associated with cognitive functions in ASD. In this line, we elaborated a systematic revision of the evidence of alterations in brain oscillations that underlie key cognitive processes that have been shown to be affected in ASD during childhood and adolescence, namely, social cognition, attention, working memory, inhibitory control, and cognitive flexibility. This knowledge could contribute to developing therapies based on NIBS to improve these processes in populations with ASD.
Differential diagnosis of frontotemporal dementia subtypes with explainable deep learning on structural MRI
Authors: Ma Da , Stocks Jane , Rosen Howard , Kantarci Kejal , Lockhart Samuel N. , Bateman James R. , Craft Suzanne , Gurcan Metin N. , Popuri Karteek , Beg Mirza Faisal , Wang Lei ,   on behalf of the ALLFTD consortium
Published: February 2024

Background

Frontotemporal dementia (FTD) represents a collection of neurobehavioral and neurocognitive syndromes that are associated with a significant degree of clinical, pathological, and genetic heterogeneity. Such heterogeneity hinders the identification of effective biomarkers, preventing effective targeted recruitment of participants in clinical trials for developing potential interventions and treatments. In the present study, we aim to automatically differentiate patients with three clinical phenotypes of FTD, behavioral-variant FTD (bvFTD), semantic variant PPA (svPPA), and nonfluent variant PPA (nfvPPA), based on their structural MRI by training a deep neural network (DNN).

Methods

Data from 277 FTD patients (173 bvFTD, 63 nfvPPA, and 41 svPPA) recruited from two multi-site neuroimaging datasets: the Frontotemporal Lobar Degeneration Neuroimaging Initiative and the ARTFL-LEFFTDS Longitudinal Frontotemporal Lobar Degeneration databases. Raw T1-weighted MRI data were preprocessed and parcellated into patch-based ROIs, with cortical thickness and volume features extracted and harmonized to control the confounding effects of sex, age, total intracranial volume, cohort, and scanner difference. A multi-type parallel feature embedding framework was trained to classify three FTD subtypes with a weighted cross-entropy loss function used to account for unbalanced sample sizes. Feature visualization was achieved through post-hoc analysis using an integrated gradient approach.

Results

The proposed differential diagnosis framework achieved a mean balanced accuracy of 0.80 for bvFTD, 0.82 for nfvPPA, 0.89 for svPPA, and an overall balanced accuracy of 0.84. Feature importance maps showed more localized differential patterns among different FTD subtypes compared to groupwise statistical mapping.

Conclusion

In this study, we demonstrated the efficiency and effectiveness of using explainable deep-learning-based parallel feature embedding and visualization framework on MRI-derived multi-type structural patterns to differentiate three clinically defined subphenotypes of FTD: bvFTD, nfvPPA, and svPPA, which could help with the identification of at-risk populations for early and precise diagnosis for intervention planning.
The effects of flux on the radiation-induced embrittlement of reactor pressure vessel steels: review of current understanding and application to high fluences
Authors: Ortner Susan , Styman Paul , Long Elliot
Published: February 2024

It is necessary to quantify the effects of flux on reactor pressure vessel steel embrittlement under neutron irradiation, if surveillance or high-flux test reactor data is used to predict vessel embrittlement occurring at lower fluxes. This is particularly important when considering embrittlement occurring during extended (60–80 years) operation for which there is no direct experience. Dedicated investigations are time-consuming and expensive even when only small flux-fluence ranges are investigated, so collating data from multiple campaigns is necessary to provide sufficient information to cover the wide range of fluxes required for vessel assessment in the long term. This paper collates and reviews such data. The review finds that flux dependences probably differ in sign and strength in different regimes (low flux and fluence, intermediate flux at low and high fluence, high flux at low and high fluence) with the regime limits affected by composition and temperature. The current understanding of diffusion processes and microstructural development are invaluable in interpreting the trends and limits. Many contradictory data sets were found, however, and not all contradictions could be dismissed as resulting from poor quality data. Suggestions are made for investigations to clarify the uncertainties. One wide-ranging model of flux effects, based on an extensive data set, is used to compare high-fluence data from different sources, to assess whether embrittlement rates accelerate after a high, threshold fluence. The model helps to identify experiments which investigated comparable flux-fluence-temperature regimes. The comparable data are split evenly between data sets supporting acceleration after a particular fluence and data sets contradicting it. The model identifies regimes in which further campaigns would clarify the causes of these contrasting observations.
New insights about endometriosis-associated ovarian cancer: pathogenesis, risk factors, prediction and diagnosis and treatment
Authors: Chen Biqing , Zhao Liping , Yang Rulin , Xu Tianmin
Published: February 2024

Previous studies have shown that the risk of malignant transformation of endometriosis in premenopausal women is approximately 1%, significantly impacting the overall well-being and quality of life of affected women. Presently, the diagnostic gold standard for endometriosis-associated ovarian cancer (EAOC) continues to be invasive laparoscopy followed by histological examination. However, the application of this technique is limited due to its high cost, highlighting the importance of identifying a non-invasive diagnostic approach. Therefore, there is a critical need to explore non-invasive diagnostic methods to improve diagnostic precision and optimize clinical outcomes for patients. This review presents a comprehensive survey of the current progress in comprehending the pathogenesis of malignant transformation in endometriosis. Furthermore, it examines the most recent research discoveries concerning the diagnosis of EAOC and emphasizes potential targets for therapeutic intervention. The ultimate objective is to improve prevention, early detection, precise diagnosis, and treatment approaches, thereby optimizing the clinical outcomes for patients.
CT-based radiomics for predicting Ki-67 expression in lung cancer: a systematic review and meta-analysis
Authors: Luo Xinmin , Zheng Renying , Zhang Jiao , He Juan , Luo Wei , Jiang Zhi , Li Qiang
Published: February 2024

Background

Radiomics, an emerging field, presents a promising avenue for the accurate prediction of biomarkers in different solid cancers. Lung cancer remains a significant global health challenge, contributing substantially to cancer-related mortality. Accurate assessment of Ki-67, a marker reflecting cellular proliferation, is crucial for evaluating tumor aggressiveness and treatment responsiveness, particularly in non-small cell lung cancer (NSCLC).

Methods

A systematic review and meta-analysis conducted following the preferred reporting items for systematic review and meta-analysis of diagnostic test accuracy studies (PRISMA-DTA) guidelines. Two authors independently conducted a literature search until September 23, 2023, in PubMed, Embase, and Web of Science. The focus was on identifying radiomics studies that predict Ki-67 expression in lung cancer. We evaluated quality using both Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and the Radiomics Quality Score (RQS) tools. For statistical analysis in the meta-analysis, we used STATA 14.2 to assess sensitivity, specificity, heterogeneity, and diagnostic values.

Results

Ten retrospective studies were pooled in the meta-analysis. The findings demonstrated that the use of computed tomography (CT) scan-based radiomics for predicting Ki-67 expression in lung cancer exhibited encouraging diagnostic performance. Pooled sensitivity, specificity, and area under the curve (AUC) in training cohorts were 0.78, 0.81, and 0.85, respectively. In validation cohorts, these values were 0.78, 0.70, and 0.81. Quality assessment using QUADAS-2 and RQS indicated generally acceptable study quality. Heterogeneity in training cohorts, attributed to factors like contrast-enhanced CT scans and specific Ki-67 thresholds, was observed. Notably, publication bias was detected in the training cohort, indicating that positive results are more likely to be published than non-significant or negative results. Thus, journals are encouraged to publish negative results as well.

Conclusion

In summary, CT-based radiomics exhibit promise in predicting Ki-67 expression in lung cancer. While the results suggest potential clinical utility, additional research efforts should concentrate on enhancing diagnostic accuracy. This could pave the way for the integration of radiomics methods as a less invasive alternative to current procedures like biopsy and surgery in the assessment of Ki-67 expression.
Efficacy of hyaluronic acid in the treatment of nasal inflammatory diseases: a systematic review and meta-analysis
Authors: Liu Huixia , Chen Yue , Wang Huan , Luo Xinyi , Xie Dengpiao , Ji Qing , Tian Li
Published: February 2024

Background: Hyaluronic acid (HA), the main component of the extracellular matrix, has the ability to promote tissue repair and regulate inflammation. It is used in otolaryngology as an adjuvant treatment to alleviate postoperative nasal symptoms. However, there is currently insufficient evidence demonstrating the therapeutic efficacy of HA for patients with nasal inflammatory diseases (NIDs). Therefore, this study aimed to evaluate the efficacy and safety of topical HA in the treatment of NID patients without receiving surgery.

Methods: In this meta-analysis, comprehensive searches were conducted in PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science. Keywords searched included “hyaluronic acid,” “sinusitis,” “allergic rhinitis,” “rhinitis,” and “randomized controlled trials (RCTs).” The Cochrane Collaboration’s “Risk of Bias Assessment” tool was used to assess the quality of the included trials, and the meta-analysis was performed using the RevMan 5.3 and STATA 15 statistical software.

Results: A total of 11 articles and 825 participants were enrolled. For the primary outcomes, the pooled results revealed that HA significantly improves nasal obstruction (SMD, −0.53; 95% CI, −0.92 to −0.14; p = 0.008; and I2 = 79%) and rhinorrhea (SMD, −0.71; 95% CI, −1.27 to −0.15; p = 0.01; and I2 = 90%) in patients with NIDs. As for the secondary outcomes, the pooled results demonstrated that when compared with the control group, HA could significantly improve nasal endoscopic scores (p < 0.05), rhinitis scores (p < 0.05), rhinomanometry (p < 0.05), nasal neutrophils (p < 0.05), and mucociliary clearance (p < 0.05). However, no significant differences were observed between the two groups regarding nasal itching, sneezing, hyposmia, quality-of-life scores, and nasal eosinophils. For the risk of bias, 54.5% and 45.5% of trials had a low risk of bias in the randomization process and deviation of the intended intervention, respectively.

Conclusion: In the present study, the results reveal that HA might ameliorate symptoms of patients with NIDs. However, more clinical trials with larger participant cohorts are required to confirm this result.

Systematic review registration number:clinicaltrials.gov, identifier CRD42023414539.
Identification of potential anti-inflammatory components in Moutan Cortex by bio-affinity ultrafiltration coupled with ultra-performance liquid chromatography mass spectrometry
Authors: Zou Caomin , Chen Qianru , Li Jiasheng , Lin Xiguang , Xue Xingyang , Cai Xinhang , Chen Yicheng , Sun Yue , Wang Shumei , Zhang Ying , Meng Jiang
Published: February 2024

Moutan Cortex (MC) has been used in treating inflammation-associated diseases and conditions in China and other Southeast Asian countries. However, the active components of its anti-inflammatory effect are still unclear. The study aimed to screen and identify potential cyclooxygenase-2 (COX-2) inhibitors in MC extract. The effect of MC on COX-2 was determined in vitro by COX-2 inhibitory assays, followed by bio-affinity ultrafiltration in combination with ultra-performance liquid chromatography-mass spectrometry (BAUF-UPLC-MS). To verify the reliability of the constructed approach, celecoxib was applied as the positive control, in contrast to adenosine which served as the negative control in this study. The bioactivity of the MC components was validated in vitro by COX-2 inhibitor assay and RAW264.7 cells. Their in vivo anti-inflammatory activity was also evaluated using LPS-induced zebrafish inflammation models. Finally, molecular docking was hired to further explore the internal interactions between the components and COX-2 residues. The MC extract showed an evident COX-2-inhibitory effect in a concentration-dependent manner. A total of 11 potential COX-2 inhibitors were eventually identified in MC extract. The COX-2 inhibitory activity of five components, namely, gallic acid (GA), methyl gallate (MG), galloylpaeoniflorin (GP), 1,2,3,6-Tetra-O-galloyl-β-D-glucose (TGG), and 1,2,3,4,6-Penta-O-galloyl-β-D-glucopyranose (PGG), were validated through both in vitro assays and experiments using zebrafish models. Besides, the molecular docking analysis revealed that the potential inhibitors in MC could effectively inhibit COX-2 by interacting with specific residues, similar to the mechanism of action exhibited by celecoxib. In conclusion, BAUF-UPLC-MS combining the molecular docking is an efficient approach to discover enzyme inhibitors from traditional herbs and understand the mechanism of action.
A pharmacovigilance study on antibody-drug conjugate (ADC)-related neurotoxicity based on the FDA adverse event reporting system (FAERS)
Authors: Tang Linlin , Sun Cuicui , Liu Wenshan , Wu Haiyan , Ding Chuanhua
Published: February 2024

Background: Antibody-drug conjugates (ADCs) are a relatively new class of anticancer agents that use monoclonal antibodies to specifically recognize tumour cell surface antigens. However, off-target effects may lead to severe adverse events. This study evaluated the neurotoxicity of ADCs using the FDA Adverse Event Reporting System (FAERS) database.

Research design and methods: Data were extracted from the FAERS database for 2004 Q1 to 2022 Q4. We analysed the clinical characteristics of ADC-related neurological adverse events (AEs). We used the reporting odds ratio (ROR) and proportional reporting ratio (PRR) for the disproportionality analysis to evaluate the potential association between AEs and ADCs.

Results: A total of 562 cases of neurological AEs were attributed to ADCs. The median age was 65 years old [(Min; Max) = 3; 92]. Neurotoxic signals were detected in patients receiving brentuximab vedotin, enfortumab vedotin, polatuzumab vedotin, trastuzumab emtansine, gemtuzumab ozogamicin, inotuzumab ozogamicin, and trastuzumab deruxtecan. The payloads of brentuximab vedotin, enfortumab vedotin, polatuzumab vedotin, and trastuzumab emtansine were microtubule polymerization inhibitors, which are more likely to develop neurotoxicity. We also found that brentuximab vedotin- and gemtuzumab ozogamicin-related neurological AEs were more likely to result in serious outcomes. The eight most common ADC-related nervous system AE signals were peripheral neuropathy [ROR (95% CI) = 16.98 (14.94–19.30), PRR (95% CI) = 16.0 (14.21–18.09)], cerebral haemorrhage [ROR (95% CI) = 9.45 (7.01–12.73), PRR (95% CI) = 9.32 (6.95–12.50)], peripheral sensory neuropathy [ROR (95% CI) = 47.87 (33.13–69.19), PRR (95% CI) = 47.43 (32.93–68.30)], polyneuropathy [ROR (95% CI) = 26.01 (18.61–36.33), PRR (95% CI) = 25.75 (18.50–35.86)], encephalopathy [ROR (95% CI) = 5.16 (3.32–8.01), PRR (95% CI) = 5.14 (3.32–7.96)], progressive multifocal leukoencephalopathy [ROR (95% CI) = 22.67 (14.05–36.58), PRR (95% CI) = 22.52 (14.01–36.21)], taste disorder [ROR (95% CI) = 26.09 (15.92–42.76), PRR (95% CI) = 25.78 (15.83–42.00)], and guillain barrier syndrome [ROR (95% CI) = 17.844 (10.11–31.51), PRR (95% CI) = 17.79 (10.09–31.35)]. The mortality rate appeared to be relatively high concomitantly with AEs in the central nervous system.

Conclusion: ADCs may increase the risk of neurotoxicity in cancer patients, leading to serious mortality. With the widespread application of newly launched ADC drugs, combining the FAERS data with other data sources is crucial for monitoring the neurotoxicity of ADCs. Further studies on the potential mechanisms and preventive measures for ADC-related neurotoxicity are necessary.
Analysis of Marchantia polymorpha–microorganism interactions: basis for understanding plant–microbe and plant–pathogen interactions
Authors: Poveda Jorge
Published: February 2024

Marchantia polymorpha is a bryophyte gaining significance as a model plant in evolutionary studies in recent years. This is attributed to its small-sequenced genome, standardized transformation methodology, global distribution, and easy and rapid in vitro culturing. As an evolutionary model, M. polymorpha contributes to our understanding of the evolution of plant defensive responses and the associated hormonal signaling pathways. Through its interaction with microorganisms, M. polymorpha serves as a valuable source of knowledge, yielding insights into new microbial species and bioactive compounds. Bibliographic analysis involved collecting, reading, and categorizing documents obtained from the Scopus and Web of Science databases using different search terms. The review was based on 30 articles published between 1995 and 2023, with Japanese and Spanish authors emerging as the most prolific contributors in this field. These articles have been grouped into four main themes: antimicrobial metabolites produced by M. polymorpha; identification and characterization of epiphytic, endophytic, and pathogenic microorganisms; molecular studies of the direct interaction between M. polymorpha and microorganisms; and plant transformation using bacterial vectors. This review highlights the key findings from these articles and identifies potential future research directions.