bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular characterization and induced changes of histone acetyltransferases in the tick Haemaphysalis longicornis in response to cold stress
Authors: Pei Tingwei , Zhang Miao , Gao Ziwen , Li Lu , Bing Ziyan , Meng Jianglei , Nwanade Chuks Fidel , Yuan Chaohui , Yu Zhijun , Liu Jingze
Published: May 2024

Background

Epigenetic modifications of histones play important roles in the response of eukaryotic organisms to environmental stress. However, many histone acetyltransferases (HATs), which are responsible for histone acetylation, and their roles in mediating the tick response to cold stress have yet to be identified. In the present study, HATs were molecularly characterized and their associations with the cold response of the tick Haemaphysalis longicornis explored.

Methods

HATs were characterized by using polymerase chain reaction (PCR) based on published genome sequences, followed by multiple bioinformatic analyses. The differential expression of genes in H. longicornis under different cold treatment conditions was evaluated using reverse transcription quantitative PCR (RT-qPCR). RNA interference was used to explore the association of HATs with the cold response of H. longicornis.

Results

Two HAT genes were identified in H. longicornis (Hl), a GCN5-related N-acetyltransferase (henceforth HlGNAT) and a type B histone acetyltransferase (henceforth HlHAT-B), which are respectively 960 base pairs (bp) and 1239 bp in length. Bioinformatics analysis revealed that HlGNAT and HlHAT-B are unstable hydrophilic proteins characterized by the presence of the acetyltransferase 16 domain and Hat1_N domain, respectively. RT-qPCR revealed that the expression of HlGNAT and HlHAT-B decreased after 3 days of cold treatment, but gradually increased with a longer period of cold treatment. The mortality rate following knockdown of HlGNAT or HlHAT-B by RNA interference, which was confirmed by RT-qPCR, significantly increased (P < 0.05) when H. longicornis was treated at the lowest lethal temperature (− 14 °C) for 2 h.

Conclusions

The findings demonstrate that HATs may play a crucial role in the cold response of H. longicornis. Thus further research is warranted to explore the mechanisms underlying the epigenetic regulation of the cold response in ticks.

Graphical Abstract
Research advances in the anti-inflammatory effects of SGLT inhibitors in type 2 diabetes mellitus
Authors: Zhang Ruining , Xie Qingxing , Lu Xi , Fan Rongping , Tong Nanwei
Published: May 2024

Diabetes mellitus is one of the most significant global burden diseases. It is well established that a chronic, systemic, low-grade inflammatory condition is strongly correlated with type 2 diabetes mellitus (T2D) and the development of target-organ damage (TOD). Sodium-glucose cotransporter inhibitors (SGLTis), novel oral drugs for the treatment of diabetes, act mainly by reducing glucose reabsorption in proximal renal tubules and/or the intestine. Several high-quality clinical trials and large observational studies have revealed that SGLTis significantly improve cardiovascular and renal outcomes in T2D patients. Increasing evidence suggests that this is closely related to their anti-inflammatory properties, which are mainly manifested by a reduction in plasma concentrations of inflammatory biomarkers. This review analyses the potential mechanisms behind the anti-inflammatory effects of SGLTis in diabetes and presents recent evidence of their therapeutic efficacy in treating diabetes and related TOD.

Graphic Abstract
The gut microbiome, resistome, and mycobiome in preterm newborn infants and mouse pups: lack of lasting effects by antimicrobial therapy or probiotic prophylaxis
Authors: Yuu Elizabeth Y. , Bührer Christoph , Eckmanns Tim , Fulde Marcus , Herz Michaela , Kurzai Oliver , Lindstedt Christin , Panagiotou Gianni , Piro Vitor C. , Radonic Aleksandar , Renard Bernhard Y. , Reuss Annicka , Siliceo Sara Leal , Thielemann Nadja , Thürmer Andrea , Vorst Kira van , Wieler Lothar H. , Haller Sebastian
Published: May 2024

Background

Enhancing our understanding of the underlying influences of medical interventions on the microbiome, resistome and mycobiome of preterm born infants holds significant potential for advancing infection prevention and treatment strategies. We conducted a prospective quasi-intervention study to better understand how antibiotics, and probiotics, and other medical factors influence the gut development of preterm infants. A controlled neonatal mice model was conducted in parallel, designed to closely reflect and predict exposures. Preterm infants and neonatal mice were stratified into four groups: antibiotics only, probiotics only, antibiotics followed by probiotics, and none of these interventions. Stool samples from both preterm infants and neonatal mice were collected at varying time points and analyzed by 16 S rRNA amplicon sequencing, ITS amplicon sequencing and whole genome shotgun sequencing.

Results

The human infant microbiomes showed an unexpectedly high degree of heterogeneity. Little impact from medical exposure (antibiotics/probiotics) was observed on the strain patterns, however, Bifidobacterium bifidum was found more abundant after exposure to probiotics, regardless of prior antibiotic administration. Twenty-seven antibiotic resistant genes were identified in the resistome. High intra-variability was evident within the different treatment groups. Lastly, we found significant effects of antibiotics and probiotics on the mycobiome but not on the microbiome and resistome of preterm infants.

Conclusions

Although our analyses showed transient effects, these results provide positive motivation to continue the research on the effects of medical interventions on the microbiome, resistome and mycobiome of preterm infants.
An inversion-based clustering approach for complex clusters
Authors: Barati Jozan Mohammad Mahdi , Lotfata Aynaz , Hamilton Howard J. , Tabesh Hamed
Published: May 2024

Background

The choice of an appropriate similarity measure plays a pivotal role in the effectiveness of clustering algorithms. However, many conventional measures rely solely on feature values to evaluate the similarity between objects to be clustered. Furthermore, the assumption of feature independence, while valid in certain scenarios, does not hold true for all real-world problems. Hence, considering alternative similarity measures that account for inter-dependencies among features can enhance the effectiveness of clustering in various applications.

Methods

In this paper, we present the Inv measure, a novel similarity measure founded on the concept of inversion. The Inv measure considers the significance of features, the values of all object features, and the feature values of other objects, leading to a comprehensive and precise evaluation of similarity. To assess the performance of our proposed clustering approach that incorporates the Inv measure, we evaluate it on simulated data using the adjusted Rand index.

Results

The simulation results strongly indicate that inversion-based clustering outperforms other methods in scenarios where clusters are complex, i.e., apparently highly overlapped. This showcases the practicality and effectiveness of the proposed approach, making it a valuable choice for applications that involve complex clusters across various domains.

Conclusions

The inversion-based clustering approach may hold significant value in the healthcare industry, offering possible benefits in tasks like hospital ranking, treatment improvement, and high-risk patient identification. In social media analysis, it may prove valuable for trend detection, sentiment analysis, and user profiling. E-commerce may be able to utilize the approach for product recommendation and customer segmentation. The manufacturing sector may benefit from improved quality control, process optimization, and predictive maintenance. Additionally, the approach may be applied to traffic management and fleet optimization in the transportation domain. Its versatility and effectiveness make it a promising solution for diverse fields, providing valuable insights and optimization opportunities for complex and dynamic data analysis tasks.
Extracellular volume-based scoring system for tracking tumor progression in pancreatic cancer patients receiving intraoperative radiotherapy
Authors: Cai Wei , Zhu Yongjian , Teng Ze , Li Dengfeng , Cong Rong , Chen Zhaowei , Ma Xiaohong , Zhao Xinming
Published: May 2024

Objectives

To investigate the value of extracellular volume (ECV) derived from portal-venous phase (PVP) in predicting prognosis in locally advanced pancreatic cancer (LAPC) patients receiving intraoperative radiotherapy (IORT) with initial stable disease (SD) and to construct a risk-scoring system based on ECV and clinical-radiological features.

Materials and methods

One hundred and three patients with LAPC who received IORT demonstrating SD were enrolled and underwent multiphasic contrast-enhanced CT (CECT) before and after IORT. ECV maps were generated from unenhanced and PVP CT images. Clinical and CT imaging features were analyzed. The independent predictors of progression-free survival (PFS) determined by multivariate Cox regression model were used to construct the risk-scoring system. Time-dependent receiver operating characteristic (ROC) curve analysis and the Kaplan–Meier method were used to evaluate the predictive performance of the scoring system.

Results

Multivariable analysis revealed that ECV, rim-enhancement, peripancreatic fat infiltration, and carbohydrate antigen 19-9 (CA19-9) response were significant predictors of PFS (all p < 0.05). Time-dependent ROC of the risk-scoring system showed a satisfactory predictive performance for disease progression with area under the curve (AUC) all above 0.70. High-risk patients (risk score ≥ 2) progress significantly faster than low-risk patients (risk score < 2) (p < 0.001).

Conclusion

ECV derived from PVP of conventional CECT was an independent predictor for progression in LAPC patients assessed as SD after IORT. The scoring system integrating ECV, radiological features, and CA19-9 response can be used as a practical tool for stratifying prognosis in these patients, assisting clinicians in developing an appropriate treatment approach.

Critical relevance statement

The scoring system integrating ECV fraction, radiological features, and CA19-9 response can track tumor progression in patients with LAPC receiving IORT, aiding clinicians in choosing individual treatment strategies and improving their prognosis.

Key Points

Predicting the progression of LAPC in patients receiving IORT is important.

Our ECV-based scoring system can risk stratifying patients with initial SD.

Appropriate prognostication can assist clinicians in developing appropriate treatment approaches.

Graphical Abstract
Determining the ideal measurement site and respiratory condition for liver transient elastography: toward clinical practice standardization
Authors: Huang Zihao , Lam Sai Kit , Cheng Lok Kan , Lin Yangmin , Zheng Yongping
Published: May 2024

Objectives

Liver transient elastography (TE) has been endorsed by the WHO as the first-line diagnostic tool for liver diseases. Although unreliable and invalid results caused by intercostal space (ICS)-associated factors (including excessive subcutaneous fat and a narrow ICS relative to the transducer size) and operator inexperience are not uncommon, no standard guidelines for ideal probe placement are currently available. Herein, we conducted a prospective observational study to identify an ideal measurement site and respiratory condition for TE by characterizing anatomical and biomechanical properties of the ICSs using ultrasound B-mode and elasticity imaging.

Methods

Intercostal ultrasound was performed pointwise at four specific sites in 59 patients to simultaneously measure the width, stiffness, and skin‒liver capsule distance (SCD) of the ICSs over the liver, under end-inspiratory and end-expiratory conditions. Intersections between the 8th ICS and anterior axillary line, the 7th ICS and anterior axillary line, the 8th ICS and mid-axillary line, and the 7th ICS and mid-axillary line were defined as Sites 1 to 4, respectively.

Results

Results indicated that Sites 2 and 3 presented greater intercostal width; Sites 3 and 4 displayed lower intercostal stiffness; Sites 2 and 3 exhibited a shorter SCD. The ICSs were significantly wider and stiffer at end-inspiration. Additionally, the liver was more easily visualized at Sites 1 and 3.

Conclusion

We recommend Site 3 for TE probe placement owing to its greater width, lower stiffness, and smaller abdominal wall thickness. Performing TE at end-inspiration is preferred to minimize transducer-rib interferences. This study paves the way toward a standardized TE examination procedure.

Critical relevance statement

A standardized measurement protocol for WHO-recommended liver TE was first established to improve the success and efficiency of the examination procedure.

Key Points

WHO-recommended TE is unreliable or fails due to intercostal space-related factors.

The 8th intercostal space on the mid-axillary line and end-inspiration are recommended.

This standardized protocol aids in handling challenging cases and simplifies operational procedures.

Graphical Abstract
Establishing a machine learning model based on dual-energy CT enterography to evaluate Crohn’s disease activity
Authors: Li Junlin , Xie Gang , Tang Wuli , Zhang Lingqin , Zhang Yue , Zhang Lingfeng , Wang Danni , Li Kang
Published: May 2024

Objectives

The simplified endoscopic score of Crohn’s disease (SES-CD) is the gold standard for quantitatively evaluating Crohn’s disease (CD) activity but is invasive. This study aimed to develop and validate a machine learning (ML) model based on dual-energy CT enterography (DECTE) to noninvasively evaluate CD activity.

Methods

We evaluated the activity in 202 bowel segments of 46 CD patients according to the SES-CD score and divided the segments randomly into training set and testing set at a ratio of 7:3. Least absolute shrinkage and selection operator (LASSO) was used for feature selection, and three models based on significant parameters were established based on logistic regression. Model performance was evaluated using receiver operating characteristic (ROC), calibration, and clinical decision curves.

Results

There were 110 active and 92 inactive bowel segments. In univariate analysis, the slope of spectral curve in the venous phases (λHU-V) has the best diagnostic performance, with an area under the ROC curve (AUC) of 0.81 and an optimal threshold of 1.975. In the testing set, the AUC of the three models established by the 7 variables to differentiate CD activity was 0.81–0.87 (DeLong test p value was 0.071–0.766, p > 0.05), and the combined model had the highest AUC of 0.87 (95% confidence interval (CI): 0.779–0.959).

Conclusions

The ML model based the DECTE can feasibly evaluate CD activity, and DECTE parameters provide a quantitative analysis basis for evaluating specific bowel activities in CD patients.

Critical relevance statement

The machine learning model based on dual-energy computed tomography enterography can be used for evaluating Crohn’s disease activity noninvasively and quantitatively.

Key Points

Dual-energy CT parameters are related to Crohn’s disease activity.

Three machine learning models effectively evaluated Crohn’s disease activity.

Combined models based on conventional and dual-energy CT have the best performance.

Graphical Abstract
Endovascular treatment in Danon disease: a case report
Authors: Jiménez-Bolaños Rayco , Hernández-Fernández Francisco , García-García Jorge , Ayo-Martín Óscar , del Rey Megias Laura , Molina-Nuevo Juan David , Segura Tomás
Published: May 2024

Background

Danon disease is a lysosomal storage disorder with X-linked inheritance. The classic triad is severe hypertrophic cardiomyopathy, myopathy, and intellectual disability, with different phenotypes between both genders. Ischemic stroke is an uncommon complication, mostly cardioembolic, related to intraventricular thrombus or atrial fibrillation, among others.

Case report

We report the case of a 14-year-old Caucasian male patient with Danon disease who suffered from an acute ischemic stroke due to occlusion in the M1 segment of the middle cerebral artery. He underwent mechanical thrombectomy, resulting in successful revascularization with satisfactory clinical outcome. We objectified the intraventricular thrombus in the absence of arrhythmic events.

Conclusion

To our knowledge, we report the first case of ischemic stroke related to Danon disease treated with endovascular treatment.
Insights into the role of adipose-derived stem cells and secretome: potential biology and clinical applications in hypertrophic scarring
Authors: Wang Menglin , Zhao Jianyu , Li Jiacheng , Meng Meng , Zhu Mengru
Published: May 2024

Scar tissue is the inevitable result of repairing human skin after it has been subjected to external destructive stimuli. It leads to localized damage to the appearance of the skin, accompanied by symptoms such as itching and pain, which reduces the quality of life of the patient and causes serious medical burdens. With the continuous development of economy and society, there is an increasing demand for beauty. People are looking forward to a safer and more effective method to eliminate pathological scarring. In recent years, adipose-derived stem cells (ADSCs) have received increasing attention from researchers. It can effectively improve pathological scarring by mediating inflammation, regulating fibroblast proliferation and activation, and vascular reconstruction. This review focuses on the pathophysiological mechanisms of hypertrophic scarring, summarizing the therapeutic effects of in vitro, in vivo, and clinical studies on the therapeutic effects of ADSCs in the field of hypertrophic scarring prevention and treatment, the latest application techniques, such as cell-free therapies utilizing ADSCs, and discussing the advantages and limitations of ADSCs. Through this review, we hope to further understand the characterization of ADSC and clarify the effectiveness of its application in hypertrophic scarring treatment, so as to provide clinical guidance.
Non-HLA angiotensin-type-1 receptor autoantibodies mediate the long-term loss of grafted neurons in Parkinson’s disease models
Authors: Rodríguez-Pérez Ana I. , Garrido-Gil Pablo , García-Garrote Maria , Muñoz Ana , Parga Juan A. , Labandeira-García Jose Luis , Rodríguez-Pallares Jannette
Published: May 2024

Background

Clinical trials have provided evidence that transplants of dopaminergic precursors, which may be replaced by new in vitro stem cell sources, can integrate into the host tissue, and alleviate motor symptoms in Parkinson´s disease (PD). In some patients, deterioration of graft function occurred several months after observing a graft-derived functional improvement. Rejection of peripheral organs was initially related to HLA-specific antibodies. However, the role of non-HLA antibodies is now considered also relevant for rejection. Angiotensin-II type-1 receptor autoantibodies (AT1-AA) act as agonists of the AT1 receptors. AT1-AA are the non-HLA antibodies most widely associated with graft dysfunction or rejection after transplantation of different solid organs and hematopoietic stem cells. However, it is not known about the presence and possible functional effects of AT1-AA in dopaminergic grafts, and the effects of treatment with AT1 receptor blockers (ARBs) such as candesartan on graft survival.

Methods

In a 6-hydroxydopamine PD rat model, we studied the short-term (10 days)- and long-term (3 months) effects of chronic treatment with the ARB candesartan on survival of grafted dopaminergic neurons and microglial graft infiltration, as well as the effects of dopaminergic denervation and grafting on serum and CSF AT1-AA levels. The expression of AT1 receptors in grafted neurons was determined by laser capture microdissection.

Results

At the early period post-grafting, the number of grafted dopaminergic neurons that survived was not significantly different between treated and untreated hosts (i.e., control rats and rats treated with candesartan), probably because, just after grafting, other deleterious factors are predominant for dopaminergic cell death, such as mechanical trauma, lack of growth factors/nutrients and ischemia. However, several months post-grafting, we observed a significantly higher number of surviving dopaminergic neurons and a higher density of striatal dopaminergic terminals in the candesartan-treated group. For several months, grafted rats showed blood and cerebrospinal fluid levels of AT1-AA higher than normal controls, and also higher AT1-AA levels than non-grafted parkinsonian rats.

Conclusions

The results suggest the use of ARBs such as candesartan in PD patients, particularly before and after dopaminergic grafts, and the need to monitor AT1-AA levels in PD patients, particularly in those candidates for dopaminergic grafting.
Multipotent/pluripotent stem cell populations in stromal tissues and peripheral blood: exploring diversity, potential, and therapeutic applications
Authors: Aprile Domenico , Patrone Deanira , Peluso Gianfranco , Galderisi Umberto
Published: May 2024

The concept of “stemness” incorporates the molecular mechanisms that regulate the unlimited self-regenerative potential typical of undifferentiated primitive cells. These cells possess the unique ability to navigate the cell cycle, transitioning in and out of the quiescent G0 phase, and hold the capacity to generate diverse cell phenotypes. Stem cells, as undifferentiated precursors endow with extraordinary regenerative capabilities, exhibit a heterogeneous and tissue-specific distribution throughout the human body. The identification and characterization of distinct stem cell populations across various tissues have revolutionized our understanding of tissue homeostasis and regeneration. From the hematopoietic to the nervous and musculoskeletal systems, the presence of tissue-specific stem cells underlines the complex adaptability of multicellular organisms. Recent investigations have revealed a diverse cohort of non-hematopoietic stem cells (non-HSC), primarily within bone marrow and other stromal tissue, alongside established hematopoietic stem cells (HSC). Among these non-HSC, a rare subset exhibits pluripotent characteristics. In vitro and in vivo studies have demonstrated the remarkable differentiation potential of these putative stem cells, known by various names including multipotent adult progenitor cells (MAPC), marrow-isolated adult multilineage inducible cells (MIAMI), small blood stem cells (SBSC), very small embryonic-like stem cells (VSELs), and multilineage differentiating stress enduring cells (MUSE). The diverse nomenclatures assigned to these primitive stem cell populations may arise from different origins or varied experimental methodologies. This review aims to present a comprehensive comparison of various subpopulations of multipotent/pluripotent stem cells derived from stromal tissues. By analysing isolation techniques and surface marker expression associated with these populations, we aim to delineate the similarities and distinctions among stromal tissue-derived stem cells. Understanding the nuances of these tissue-specific stem cells is critical for unlocking their therapeutic potential and advancing regenerative medicine. The future of stem cells research should prioritize the standardization of methodologies and collaborative investigations in shared laboratory environments. This approach could mitigate variability in research outcomes and foster scientific partnerships to fully exploit the therapeutic potential of pluripotent stem cells.
Distance plus attention for binding affinity prediction
Authors: Rahman Julia , Newton M. A. Hakim , Ali Mohammed Eunus , Sattar Abdul
Published: May 2024

Protein-ligand binding affinity plays a pivotal role in drug development, particularly in identifying potential ligands for target disease-related proteins. Accurate affinity predictions can significantly reduce both the time and cost involved in drug development. However, highly precise affinity prediction remains a research challenge. A key to improve affinity prediction is to capture interactions between proteins and ligands effectively. Existing deep-learning-based computational approaches use 3D grids, 4D tensors, molecular graphs, or proximity-based adjacency matrices, which are either resource-intensive or do not directly represent potential interactions. In this paper, we propose atomic-level distance features and attention mechanisms to capture better specific protein-ligand interactions based on donor-acceptor relations, hydrophobicity, and $$\pi $$
π
-stacking atoms. We argue that distances encompass both short-range direct and long-range indirect interaction effects while attention mechanisms capture levels of interaction effects. On the very well-known CASF-2016 dataset, our proposed method, named Distance plus Attention for Affinity Prediction (DAAP), significantly outperforms existing methods by achieving Correlation Coefficient (R) 0.909, Root Mean Squared Error (RMSE) 0.987, Mean Absolute Error (MAE) 0.745, Standard Deviation (SD) 0.988, and Concordance Index (CI) 0.876. The proposed method also shows substantial improvement, around 2% to 37%, on five other benchmark datasets. The program and data are publicly available on the website https://gitlab.com/mahnewton/daap.

Scientific Contribution Statement

This study innovatively introduces
distance-based features to predict protein-ligand binding affinity, capitalizing on
unique molecular interactions. Furthermore, the incorporation of protein sequence
features of specific residues enhances the model’s proficiency in capturing intricate
binding patterns. The predictive capabilities are further strengthened through the
use of a deep learning architecture with attention mechanisms, and an ensemble
approach, averaging the outputs of five models, is implemented to ensure robust
and reliable predictions.
InChI isotopologue and isotopomer specifications
Authors: Moseley Hunter N. B. , Rocca-Serra Philippe , Salek Reza M. , Arita Masanori , Schymanski Emma L.
Published: May 2024

This work presents a proposed extension to the International Union of Pure and Applied Chemistry (IUPAC) International Chemical Identifier (InChI) standard that allows the representation of isotopically-resolved chemical entities at varying levels of ambiguity in isotope location. This extension includes an improved interpretation of the current isotopic layer within the InChI standard and a new isotopologue layer specification for representing chemical intensities with ambiguous isotope localization. Both improvements support the unique isotopically-resolved chemical identification of features detected and measured in analytical instrumentation, specifically nuclear magnetic resonance and mass spectrometry.

Scientific contribution

This new extension to the InChI standard would enable improved annotation of analytical datasets characterizing chemical entities, supporting the FAIR (Findable, Accessible, Interoperable, and Reusable) guiding principles of data stewardship for chemical datasets, ultimately promoting Open Science in chemistry.
Multifunctional roles of γ-enolase in the central nervous system: more than a neuronal marker
Authors: Horvat Selena , Kos Janko , Pišlar Anja
Published: May 2024

Enolase, a multifunctional protein with diverse isoforms, has generally been recognized for its primary roles in glycolysis and gluconeogenesis. The shift in isoform expression from α-enolase to neuron-specific γ-enolase extends beyond its enzymatic role. Enolase is essential for neuronal survival, differentiation, and the maturation of neurons and glial cells in the central nervous system. Neuron-specific γ-enolase is a critical biomarker for neurodegenerative pathologies and neurological conditions, not only indicating disease but also participating in nerve cell formation and neuroprotection and exhibiting neurotrophic-like properties. These properties are precisely regulated by cysteine peptidase cathepsin X and scaffold protein γ1-syntrophin. Our findings suggest that γ-enolase, specifically its C-terminal part, may offer neuroprotective benefits against neurotoxicity seen in Alzheimer's and Parkinson's disease. Furthermore, although the therapeutic potential of γ-enolase seems promising, the effectiveness of enolase inhibitors is under debate. This paper reviews the research on the roles of γ-enolase in the central nervous system, especially in pathophysiological events and the regulation of neurodegenerative diseases.
Pulmonary redox imbalance drives early fibroproliferative response in moderate/severe coronavirus disease-19 acute respiratory distress syndrome and impacts long-term lung abnormalities
Authors: Yang Chun , Tan Yuanyuan , Li Zihao , Hu Lei , Chen Yuanyuan , Zhu Shouliang , Hu Jiawei , Huai Tingting , Li Mingqing , Zhang Guobin , Rao Dewang , Fei Guanghe , Shao Min , Ding Zhenxing
Published: May 2024

Background

COVID-19-associated pulmonary fibrosis remains frequent. This study aimed to investigate pulmonary redox balance in COVID-19 ARDS patients and possible relationship with pulmonary fibrosis and long-term lung abnormalities.

Methods

Baseline data, chest CT fibrosis scores, N-terminal peptide of alveolar collagen III (NT-PCP-III), transforming growth factor (TGF)-β1, superoxide dismutase (SOD), reduced glutathione (GSH), oxidized glutathione (GSSG) and malondialdehyde (MDA) in bronchoalveolar lavage fluid (BALF) were first collected and compared between SARS-CoV-2 RNA positive patients with moderate to severe ARDS (n = 65, COVID-19 ARDS) and SARS-CoV-2 RNA negative non-ARDS patients requiring mechanical ventilation (n = 63, non-ARDS). Then, correlations between fibroproliferative (NT-PCP-III and TGF-β1) and redox markers were analyzed within COVID-19 ARDS group, and comparisons between survivor and non-survivor subgroups were performed. Finally, follow-up of COVID-19 ARDS survivors was performed to analyze the relationship between pulmonary abnormalities, fibroproliferative and redox markers 3 months after discharge.

Results

Compared with non-ARDS group, COVID-19 ARDS group had significantly elevated chest CT fibrosis scores (p < 0.001) and NT-PCP-III (p < 0.001), TGF-β1 (p < 0.001), GSSG (p < 0.001), and MDA (p < 0.001) concentrations on admission, while decreased SOD (p < 0.001) and GSH (p < 0.001) levels were observed in BALF. Both NT-PCP-III and TGF-β1 in BALF from COVID-19 ARDS group were directly correlated with GSSG (p < 0.001) and MDA (p < 0.001) and were inversely correlated with SOD (p < 0.001) and GSH (p < 0.001). Within COVID-19 ARDS group, non-survivors (n = 28) showed significant pulmonary fibroproliferation (p < 0.001) with more severe redox imbalance (p < 0.001) than survivors (n = 37). Furthermore, according to data from COVID-19 ARDS survivor follow-up (n = 37), radiographic residual pulmonary fibrosis and lung function impairment improved 3 months after discharge compared with discharge (p < 0.001) and were associated with early pulmonary fibroproliferation and redox imbalance (p < 0.01).

Conclusions

Pulmonary redox imbalance occurring early in COVID-19 ARDS patients drives fibroproliferative response and increases the risk of death. Long-term lung abnormalities post-COVID-19 are associated with early pulmonary fibroproliferation and redox imbalance.

Graphical abstract
Comparison of the prognosis among in-hospital survivors of cardiogenic shock based on etiology: AMI and Non-AMI
Authors: Chien Shih-Chieh , Wang Cheng-An , Liu Hung-Yi , Lin Chao-Feng , Huang Chun-Yao , Chien Li-Nien
Published: May 2024

Background

Current data on post-discharge mortality and rehospitalization is still insufficient among in-hospital survivors of cardiogenic shock (CS), including acute myocardial infarction (AMI) and non-AMI survivors.

Methods

Patients with CS who survived after hospital discharge were selected from the Taiwan National Health Insurance Research Database. Each patient was followed up at 3-year intervals. Mortality and rehospitalization were analyzed using Kaplan-Meier curves and Cox regression models.

Results

There were 16,582 eligible patients. Of these, 42.4% and 57.6% were AMI-CS and non-AMI-CS survivors, respectively. The overall mortality and rehospitalization rates were considerably high, with reports of 7.0% and 22.1% at 30 days, 24.5% and 58.2% at 1 year, and 38.9% and 73.0% at 3 years, respectively, among in-hospital CS survivors. Cardiovascular (CV) problems caused approximately 40% mortality and 60% rehospitalization. Overall, the non-AMI-CS group had a higher mortality burden than the AMI-CS group owing to older age and a higher prevalence of comorbidities. In multivariable models, the non-AMI-CS group exhibited a lower risk of all-cause mortality (adjusted hazard ratio [aHR] 0.69, 95% confidence interval [CI] 0.60 to 0.78) and CV mortality (aHR 0.65, 95% CI 0.54 to 0.78) compared to the AMI-CS group. However, these risks diminished and even reversed after one year (aHR 1.13, 95% CI 1.03 to 1.25 for all-cause mortality; aHR 1.27, 95% CI 1.09 to 1.49 for CV mortality).This reversal was not observed in all-cause and CV rehospitalization. For rehospitalization, AMI-CS was associated with the risk of CV rehospitalization in the entire observation period (aHR:0.80, 95% CI:0.76–0.84).

Conclusions

In-hospital AMI-CS survivors had an increased risk of CV rehospitalization and 30-day mortality, whereas those with non-AMI-CS had a greater mortality risk after 1-year follow-up.
Cefiderocol in Difficult-to-Treat Nf-GNB in ICU Settings
Authors: Vacheron Charles-Hervé , Kaas Anne , Rasigade Jean-Philippe , Aubrun Frederic , Argaud Laurent , Balanca Baptiste , Fellahi Jean-Luc , Richard Jean Christophe , Lukaszewicz Anne-Claire , Wallet Florent , Dauwalder Olivier , Friggeri Arnaud
Published: May 2024

Background

The efficacy and safety of cefiderocol in ICU patients with difficult-to-treat resistance (DTR) non-fermenting Gram-negative bacteria (Nf-GNB) are not as well-established. Consequently, we conducted a cohort study to compare Cefiderocol with the Best Available Therapy (BAT) in ICU patients.

Methods

We included adult patients from 9 different ICUs, including a burn ICU unit, from 2019 to 2023 treated with Cefiderocol for DTR Nf-GNB isolated from the blood or lungs. We matched each patient at a 1:2 ratio based on the same DTR Nf-GBN isolated pathogen, and when possible, within the same type of ICU (burn unit or not). The primary endpoint of the study was the clinical cure at 15 days, with secondary endpoints including clinical cure at 30 days, relapse, and in-ICU mortality. For each outcome, adjusted odds ratios were estimated using bidirectional stepwise regression in a final model, which included 13 preselected confounders.

Results

We included 27 patients with cefiderocol, matched with 54 patients receiving the BAT. Four patients were not exactly matched on the type of ICU unit. Characteristics were comparable between groups, mostly male with a Charlson Comorbidity Index of 3 [1–5], and 28% had immunosuppression. Cefiderocol patients were most likely to have higher number of antibiotic lines. The main DTR Nf-GNB identified was Pseudomonas aeruginosa (81.5%), followed by Acinetobater baumanii (14.8%) and Stenotrophomonas maltophilia (3.7%). Pneumonia was the identified infection in 21 (78.8%) patients in the Cefiderocol group and in 51 (94.4%) patients in the BAT group (p = 0.054). Clinical cure at 15 and 30-day and the in-ICU mortality was comparable between groups, however relapse was higher in the cefiderocol group (8-29.6% vs. 4-7.4%;aOR 10.06[1.96;51.53])

Conclusion

Cefiderocol did not show an improvement in clinical cure or mortality rates compared to BAT in the treatment of DTR Nf-GNB, but it was associated with a higher relapse rate.
Base excess (BE): reloaded
Authors: Zander Rolf
Published: May 2024

The base excess value (BE, mmol/L), not standard base excess (SBE), correctly calculated including pH, pCO2 (mmHg), sO2 (%) and cHb (g/dl) is a diagnostic tool for several in vivo events, e.g., mortality after multiple trauma or shock, acidosis, bleeding, clotting, artificial ventilation. In everyday clinical practice a few microlitres of blood (arterial, mixed venous or venous) are sufficient for optimal diagnostics of any metabolic acidosis or alkalosis.

The same applies to a therapeutic tool—then referred to as potential base excess (BEpot)—for several in vitro assessments, e.g., solutions for infusion, sodium bicarbonate, blood products, packed red blood cells, plasma. Thus, BE or BEpot has been a parameter with exceptional clinical significance since 2007.
A dosiomics model for prediction of radiation-induced acute skin toxicity in breast cancer patients: machine learning-based study for a closed bore linac
Authors: Saadatmand Pegah , Mahdavi Seied Rabi , Nikoofar Alireza , Jazaeri Seyede Zohreh , Ramandi Fahime Lamei , Esmaili Golbarg , Vejdani Soheil
Published: May 2024

Background

Radiation induced acute skin toxicity (AST) is considered as a common side effect of breast radiation therapy. The goal of this study was to design dosiomics-based machine learning (ML) models for prediction of AST, to enable creating optimized treatment plans for high-risk individuals.

Methods

Dosiomics features extracted using Pyradiomics tool (v3.0.1), along with treatment plan-derived dose volume histograms (DVHs), and patient-specific treatment-related (PTR) data of breast cancer patients were used for modeling. Clinical scoring was done using the Common Terminology Criteria for Adverse Events (CTCAE) V4.0 criteria for skin-specific symptoms. The 52 breast cancer patients were grouped into AST 2 + (CTCAE ≥ 2) and AST 2 − (CTCAE < 2) toxicity grades to facilitate AST modeling. They were randomly divided into training (70%) and testing (30%) cohorts. Multiple prediction models were assessed through multivariate analysis, incorporating different combinations of feature groups (dosiomics, DVH, and PTR) individually and collectively. In total, seven unique combinations, along with seven classification algorithms, were considered after feature selection. The performance of each model was evaluated on the test group using the area under the receiver operating characteristic curve (AUC) and f1-score. Accuracy, precision, and recall of each model were also studied. Statistical analysis involved features differences between AST 2 − and AST 2 + groups and cutoff value calculations.

Results

Results showed that 44% of the patients developed AST 2 + after Tomotherapy. The dosiomics (DOS) model, developed using dosiomics features, exhibited a noteworthy improvement in AUC (up to 0.78), when spatial information is preserved in the dose distribution, compared to DVH features (up to 0.71). Furthermore, a baseline ML model created using only PTR features for comparison with DOS models showed the significance of dosiomics in early AST prediction. By employing the Extra Tree (ET) classifiers, the DOS + DVH + PTR model achieved a statistically significant improved performance in terms of AUC (0.83; 95% CI 0.71–0.90), accuracy (0.70), precision (0.74) and sensitivity (0.72) compared to other models.

Conclusions

This study confirmed the benefit of dosiomics-based ML in the prediction of AST. However, the combination of dosiomics, DVH, and PTR yields significant improvement in AST prediction. The results of this study provide the opportunity for timely interventions to prevent the occurrence of radiation induced AST.
The impact of inhalation injury on fluid resuscitation in major burn patients: a 10-year multicenter retrospective study
Authors: Xiao Shuao , Pan Zeping , Li Hang , Zhang Yuheng , Li Tian , Zhang Hao , Ning Jinbin
Published: May 2024

Background

It remains unclear whether additional fluid supplementation is necessary during the acute resuscitation period for patients with combined inhalational injury (INHI) under the guidance of the Third Military Medical University (TMMU) protocol.

Methods

A 10-year multicenter, retrospective cohort study, involved patients with burns ≥ 50% total burn surface area (TBSA) was conducted. The effect of INHI, INHI severity, and tracheotomy on the fluid management in burn patients was assessed. Cumulative fluid administration, cumulative urine output, and cumulative fluid retention within 72 h were collected and systematically analyzed.

Results

A total of 108 patients were included in the analysis, 85 with concomitant INHI and 23 with thermal burn alone. There was no significant difference in total fluid administration during the 72-h post-burn between the INHI and non-INHI groups. Although no difference in the urine output and fluid retention was shown in the first 24 h, the INHI group had a significantly lower cumulative urine output and a higher cumulative fluid retention in the 48-h and 72-h post-burn (all p < 0.05). In addition, patients with severe INHI exhibited a significantly elevated incidence of complications (Pneumonia, 47.0% vs. 11.8%, p = 0.012), (AKI, 23.5% vs. 2.9%, p = 0.037). For patients with combined INHI, neither the severity of INHI nor the presence of a tracheotomy had any significant influence on fluid management during the acute resuscitation period.

Conclusions

Additional fluid administration may be unnecessary in major burn patients with INHI under the guidance of the TMMU protocol.
Unveiling the emerging role of curcumin to alleviate ochratoxin A-induced muscle toxicity in grass carp (Ctenopharyngodon idella): in vitro and in vivo studies
Authors: Zhao Piao , Feng Lin , Jiang Weidan , Wu Pei , Liu Yang , Ren Hongmei , Jin Xiaowan , Zhang Lu , Mi Haifeng , Zhou Xiaoqiu
Published: May 2024

Background

Ochratoxin A (OTA), a globally abundant and extremely hazardous pollutant, is a significant source of contamination in aquafeeds and is responsible for severe food pollution. The developmental toxicity of OTA and the potential relieving strategy of natural products remain unclear. This study screened the substance curcumin (Cur), which had the best effect in alleviating OTA inhibition of myoblast proliferation, from 96 natural products and investigated its effect and mechanism in reducing OTA myotoxicity in vivo and in vitro.

Methods

A total of 720 healthy juvenile grass carp, with an initial average body weight of 11.06 ± 0.05 g, were randomly assigned into 4 groups: the control group (without OTA and Cur), 1.2 mg/kg OTA group, 400 mg/kg Cur group, and 1.2 mg/kg OTA + 400 mg/kg Cur group. Each treatment consisted of 3 replicates (180 fish) for 60 d.

Results

Firstly, we cultured, purified, and identified myoblasts using the tissue block culture method. Through preliminary screening and re-screening of 96 substances, we examined cell proliferation-related indicators such as cell viability and ultimately found that Cur had the best effect. Secondly, Cur could alleviate OTA-inhibited myoblast differentiation and myofibrillar development-related proteins (MyoG and MYHC) in vivo and in vitro and improve the growth performance of grass carp. Then, Cur could also promote the expression of OTA-inhibited protein synthesis-related proteins (S6K1 and TOR), which was related to the activation of the AKT/TOR signaling pathway. Finally, Cur could downregulate the expression of OTA-enhanced protein degradation-related genes (murf1, foxo3a, and ub), which was related to the inhibition of the FoxO3a signaling pathway.

Conclusions

In summary, our data demonstrated the effectiveness of Cur in alleviating OTA myotoxicity in vivo and in vitro. This study confirms the rapidity, feasibility, and effectiveness of establishing a natural product screening method targeting myoblasts to alleviate fungal toxin toxicity.

Graphical Abstract
Association between problematic social networking use and anxiety symptoms: a systematic review and meta-analysis
Authors: Du Mingxuan , Zhao Chengjia , Hu Haiyan , Ding Ningning , He Jiankang , Tian Wenwen , Zhao Wenqian , Lin Xiujian , Liu Gaoyang , Chen Wendan , Wang ShuangLiu , Wang Pengcheng , Xu Dongwu , Shen Xinhua , Zhang Guohua
Published: May 2024

A growing number of studies have reported that problematic social networking use (PSNU) is strongly associated with anxiety symptoms. However, due to the presence of multiple anxiety subtypes, existing research findings on the extent of this association vary widely, leading to a lack of consensus. The current meta-analysis aimed to summarize studies exploring the relationship between PSNU levels and anxiety symptoms, including generalized anxiety, social anxiety, attachment anxiety, and fear of missing out. 209 studies with a total of 172 articles were included in the meta-analysis, involving 252,337 participants from 28 countries. The results showed a moderately positive association between PSNU and generalized anxiety (GA), social anxiety (SA), attachment anxiety (AA), and fear of missing out (FoMO) respectively (GA:r = 0.388, 95%CI[0.362, 0.413]; SA:r = 0.437, 95%CI[0.395, 0.478]; AA:r = 0.345, 95%CI[0.286, 0.402]; FoMO:r = 0.496, 95%CI[0.461, 0.529]), and there were different regulatory factors between PSNU and different anxiety subtypes. This study provides the first comprehensive estimate of the association of PSNU with multiple anxiety subtypes, which vary by time of measurement, region, gender, and measurement tool.
Circulating long non-coding RNAs detection after heart transplantation and its accuracy in the diagnosis of acute cardiac rejection
Authors: Pérez-Carrillo Lorena , Giménez-Escamilla Isaac , González-Torrent Irene , Delgado-Arija Marta , Sánchez-Lázaro Ignacio , García-Manzanares María , Martínez-Dolz Luis , Portolés Manuel , Tarazón Estefanía , Roselló-Lletí Esther
Published: May 2024

Long non-coding RNAs (lncRNAs) are closely implicated in biological processes and diseases with high inflammatory components. These molecules exhibit significant temporal and tissue specificity. However, the expression and function of lncRNAs have not been studied in patients after heart transplantation. Thus, we aimed to identify circulating lncRNAs in these patients and evaluate their diagnostic capacity as potential biomarkers for the non-invasive detection of acute cellular rejection (ACR). For them, we performed a transcriptomic study based on ncRNA-seq technology to detect lncRNAs in serum samples, matched to routine endomyocardial biopsies, from patients without rejection episode (0R, n = 12) and with mild (1R, n = 16) or moderate-severe (≥ 2R, n = 12) ACR. We identified 11,062 circulating lncRNAs in the serum of patients after heart transplantation. Moreover, 6 lncRNAs showed statistically significant expression when the different ACR grades were compared. Among them, AC008105.3, AC006525.1, AC011455.8, AL359220.1, and AC025279.1 had relevant diagnostic capacity for detection of ≥ 2R (AUC of 0.850 to 1.000) and 1R (AUC of 0.750 to 0.854) grades, along with high specificity and positive predictive values (≥ 83%). In addition, AL359220.1 and AC025279.1 were independent predictors for the presence of moderate-severe ACR (odds ratio = 31.132, p < 0.01 and C statistic = 0.939, p < 0.0001; odds ratio = 18.693, p < 0.05 and C statistic = 0.902, p < 0.001; respectively). In conclusion, we describe, for the first time, circulating lncRNAs after heart transplantation as potential candidates for non-invasive detection of ACR. AL359220.1 and AC025279.1 showed excellent diagnostic capability correlating with the severity episode and were strong independent predictors of rejection.