bluuebunny/crossref_metadata_2025 huggingface dataset:
Utilizing exosomes as sparking clinical biomarkers and therapeutic response in acute myeloid leukemia
Authors: Wang Wandi , Wu Xiaofang , Zheng Jiamian , Yin Ran , Li Yangqiu , Wu Xiuli , Xu Ling , Jin Zhenyi
Published: January 2024

Acute myeloid leukemia (AML) is a malignant clonal tumor originating from immature myeloid hematopoietic cells in the bone marrow with rapid progression and poor prognosis. Therefore, an in-depth exploration of the pathogenesis of AML can provide new ideas for the treatment of AML. In recent years, it has been found that exosomes play an important role in the pathogenesis of AML. Exosomes are membrane-bound extracellular vesicles (EVs) that transfer signaling molecules and have attracted a large amount of attention, which are key mediators of intercellular communication. Extracellular vesicles not only affect AML cells and normal hematopoietic cells but also have an impact on the bone marrow microenvironment and immune escape, thereby promoting the progression of AML and leading to refractory relapse. It is worth noting that exosomes and the various molecules they contain are expected to become the new markers for disease monitoring and prognosis of AML, and may also function as drug carriers and vaccines to enhance the treatment of leukemia. In this review, we mainly summarize to reveal the role of exosomes in AML pathogenesis, which helps us elucidate the application of exosomes in AML diagnosis and treatment.
Harnessing filamentous phages for enhanced stroke recovery
Authors: Li Yang , Yang Kai-di , Kong De-cai , Li Xiao-meng , Duan Hao-yu , Ye Jun-feng
Published: January 2024

Stroke poses a critical global health challenge, leading to substantial morbidity and mortality. Existing treatments often miss vital timeframes and encounter limitations due to adverse effects, prompting the pursuit of innovative approaches to restore compromised brain function. This review explores the potential of filamentous phages in enhancing stroke recovery. Initially antimicrobial-centric, bacteriophage therapy has evolved into a regenerative solution. We explore the diverse role of filamentous phages in post-stroke neurological restoration, emphasizing their ability to integrate peptides into phage coat proteins, thereby facilitating recovery. Experimental evidence supports their efficacy in alleviating post-stroke complications, immune modulation, and tissue regeneration. However, rigorous clinical validation is essential to address challenges like dosing and administration routes. Additionally, genetic modification enhances their potential as injectable biomaterials for complex brain tissue issues. This review emphasizes innovative strategies and the capacity of filamentous phages to contribute to enhanced stroke recovery, as opposed to serving as standalone treatment, particularly in addressing stroke-induced brain tissue damage.
The dynamic mechanism of scientific and technological innovation in China’s marine biomedical industry
Authors: Fu Xiu-Mei , Tan Yan-Xin , Liu Ying , Han Ying-Hui , Qi Qiao-Qiao , Li Jing-Hang , Lin Chun-Yu
Published: January 2024

As one of the important forces promoting the development of the marine economy, the marine biomedical industry (MBI) shows typical knowledge and technology-intensive characteristics. It is of great significance to explore the industrial innovation dynamic mechanism for breaking through the bottleneck of innovative development as well as achieving high-quality development. This paper constructed a system dynamics model for scientific and technological innovation (STI) in the MBI and then explored the dynamic mechanism of STI in the industry through simulation. The study found that, in the innovation environment subsystem, the two factors of the intellectual property protection intensity and the government’s scientific research funding input had the most significant positive driving effects on STI of the MBI; the promotion of government education funding input showed a significant strengthening trend over time, while the marine environmental regulation intensity had comparatively little effect on the level of STI. In the subsystem of innovation input, both innovation funding input and innovation personnel input were the direct driving forces for the improvement of the STI level. And enterprises played a dominant role in STI because the STI level of the MBI was more sensitive to the changes in enterprise innovation input. Compared with the individual factor input, the synergistic promotion effect of multiple factors is more significant. In addition, it was found that there was a low conversion rate of scientific research achievements in China’s MBI by analyzing the influence of various factors changing on technological output and economic output. Based on the research results, this paper puts forward corresponding policy suggestions in order to provide theoretical support and a practical basis for promoting the technological innovation level of China’s MBI as well as references for other countries.
The future of cell-instructive biomaterials for tissue regeneration–a perspective from early career clinician-scientists
Authors: Rangel Rodrigo , Swanson W. Benton , Wu David T.
Published: January 2024

Cell-instructive biomaterials are an essential component in tissue engineering and regenerative medicine. In the past three decades since the term “Tissue Engineering” was coined, researchers have made significant progress towards regenerating disease or damage tissues and organs by combining innovations in biomaterials, signaling molecules and cell therapies. However, challenges persist including limitations in properties of cell-instructive biomaterials, lack of advanced manufacturing technologies for precise spatiotemporal control of key players in tissue engineering, and hurdles in clinical translation and regulatory process. In this perspective article, we briefly review the current state of the field including the evolution in our understanding of the role biomaterial mechanics and scaffolding architecture, development of self-healing and modular biomaterials, and progress in advanced manufacturing technologies such as 3D bioprinting. In addition, we discuss about how innovation in research technologies including multi-omics and spatial biology, and advanced imaging modalities may pave the way for enhancing our understanding about cell-biomaterial interactions. Finally, we present our perspective as early career clinicians and researchers on the key role and potential impact that clinician-scientists can generate in the development, validation, clinical translation and adoption of the next-generation of cell-instructive biomaterials for application in engineering tissues and organs to impact human health.
Analysis of clinical characteristics and factors influencing herpes simplex virus keratitis
Authors: Zhang Shuai , Mi Jinhua , Ge Shengmei , Wang Guoqiang , Zhou Zhongyou , Zhao Yantao , Zhao Yan
Published: January 2024

Objective

To investigate the clinical characteristics and factors associated with herpes simplex virus keratitis.

Methods

Patients with herpes simplex virus keratitis who came to our hospital from January 2018 to June 2022 were selected and divided into a good prognosis group and a poor prognosis group according to their prognosis. The clinical data of the two groups were compared, and univariate/multivariate logistic regression was used to analyze the factors influencing the poor prognosis of herpes simplex virus keratitis.

Results

A one-way analysis of variance showed that, compared with the good prognosis group, the poor prognosis group had more elderly patients and a longer course of disease, and the difference was statistically significant (p < 0.05). There were significant differences in the types of patients between the two groups (p < 0.05). Univariate logistic regression analysis also showed that age (≥65 years) (OR: 1.557, 95%CI: 1.081–2.183, p < 0.05), course of disease (> 7 months) (OR: 1.303, 95%CI: 1.003–1.829, p < 0.05), epithelial type (OR: 2.321, 95%CI: 1.198–4.321, p < 0.05), and stromal type (OR: 2.536, 95%CI: 1.672–3.871, p < 0.05) were risk factors for poor prognosis. Multivariate logistic regression analysis showed that age (≥65 years) (OR: 1.656, 95%CI: 1.168–2.357, p < 0.05) and course of disease (> 7 months) (OR: 1.461, 95%CI: 1.031–2.001, p < 0.05) were independent risk factors for the prognosis of herpes simplex keratitis.

Conclusion

The clinical symptoms of herpes simplex virus keratitis include corneal opacity, corneal posterior elastic layer folds, corneal infiltration, posterior corneal mass, corneal edema, and ocular pain. Age and course of disease are important factors in the prognosis of herpes simplex virus keratitis.
Liver cirrhosis and complications from the perspective of dysbiosis
Authors: Nie Guole , Zhang Honglong , Xie Danna , Yan Jun , Li Xun
Published: January 2024

The gut-liver axis refers to the intimate relationship and rigorous interaction between the gut and the liver. The intestinal barrier’s integrity is critical for maintaining liver homeostasis. The liver operates as a second firewall in this interaction, limiting the movement of potentially dangerous compounds from the gut and, as a result, contributing in barrier management. An increasing amount of evidence shows that increased intestinal permeability and subsequent bacterial translocation play a role in liver damage development. The major pathogenic causes in cirrhotic individuals include poor intestinal permeability, nutrition, and intestinal flora dysbiosis. Portal hypertension promotes intestinal permeability and bacterial translocation in advanced liver disease, increasing liver damage. Bacterial dysbiosis is closely related to the development of cirrhosis and its related complications. This article describes the potential mechanisms of dysbiosis in liver cirrhosis and related complications, such as spontaneous bacterial peritonitis, hepatorenal syndrome, portal vein thrombosis, hepatic encephalopathy, and hepatocellular carcinoma, using dysbiosis of the intestinal flora as an entry point.
Perinatal outcome and timing of selective fetal reduction in dichorionic diamniotic twin pregnancies: a single-center retrospective study
Authors: Zou Gang , Ji Qingfang , Chen Jianping , Zhang Luye , Sun Qianqian , Shi Yaqi , Yang Yingjun , Zhou Fenhe , Wei Xing , Sun Luming
Published: January 2024

Objective

The study aimed to evaluate the pregnancy outcomes of dichorionic diamniotic twin pregnancies that were reduced to singletons at different gestational ages.

Study design

This was a retrospective cohort study of twin pregnancies that underwent fetal reduction to singletons in a single tertiary referral center between 2011 and 2020. A total of 433 cases were included. The cohort was divided into five groups according to gestational age at surgery: Group A: <16 weeks (125 cases); Group B: 16–19+6 weeks (80 cases); Group C: 20–23+6 weeks (74 cases); Group D: 24–26+6 weeks (48 cases); and Group E: ≥27 weeks (106 cases). Outcome data were obtained by reviewing the electronic medical records or interviews.

Results

Selective reduction was technically successful. The clinical characteristics of the population were not different. The overall live birth rate and the survival rate were 96.5 and 95.4%, respectively. Although the rate of spontaneous miscarriage was comparable, gestational age at delivery significantly differed among groups (p < 0.001). Additionally, there was a trend that gestational age at delivery decreased with the increasing gestational age at surgery in Groups A, B, C, and D, whereas gestational age at delivery in Group E was later than that in Group D. In Groups A, B, C, and D, the rates of preterm birth at <32 weeks and <34 weeks increased with the increasing gestational age at surgery, while the rates in Group E were significantly lower than that in Group D. Regression analysis showed that timing of reduction may be an independent factor after adjusting for maternal age, parity, pre-pregnancy BMI, ART, and cervical length.

Conclusion

Selective reduction performed by experienced hands for a dizygotic abnormal twin is safe and effective. Gestational age at surgery (<26+6 weeks) was inversely correlated with gestational age at delivery and positively with the rate of preterm birth. Reduction after 27 weeks, where legal, can be performed with a good outcome for the retained fetus.
Long-term bilateral change in pain and sensitivity to high-frequency cutaneous electrical stimulation in healthy subjects depends on stimulus modality: a dermatomal examination
Authors: Escobar-Sánchez Isabel , Ríos-León Marta , Taylor Julian
Published: January 2024

Introduction

Contradictory changes in pain and sensitivity at long-term following cutaneous 100 Hz high frequency stimulation (HFS) have been previously observed. Thus, we aimed to document long-lasting changes in multimodal sensitivity following HFS, and factors influencing them.

Methods

Long-lasting changes were assessed with mechanical [brush, von Frey filament (588.2 mN)] and thermal [heat (40°C)/cold (25°C)] bedside sensory testing, and electrical TS (0.2 ms single electrical stimuli), at the homotopic (ipsilateral C6 dermatome), adjacent heterotopic (ipsilateral C5 and C7 dermatomes) and contralateral (contralateral C6 dermatomes) dermatomal sites in a single testing session. TS were applied before and after application of 100 Hz HFS at the ipsilateral C6 dermatome. Subjects rated their sensation and pain intensity to TS, and completed questionnaires related to pain descriptors and quality of life.

Results

Long-lasting changes in mechanical and cold sensitivity was detected up to 45 min after HFS at homotopic C6 dermatome, and a temporary increase in cold sensitivity at 20 min in the contralateral C6 dermatome (p < 0.05). A slow development of bilateral depotentiation to electrical pain TS was also detected from 40 min after HFS (p < 0.05). Higher HFS-induced mechanical and cold sensitivity was identified in women (p < 0.05). Age and quality of life were associated with pain intensity (p < 0.05).

Conclusion

Long-term unilateral and bilateral changes in sensation and pain following electrical HFS have been found. These findings may suggest a new insight into the development of persistent pain mechanisms. Further studies are now needed.
Context-aware SAR image ship detection and recognition network
Authors: Li Chao , Yue Chenke , Li Hanfu , Wang Zhile
Published: January 2024

With the development of deep learning, synthetic aperture radar (SAR) ship detection and recognition based on deep learning have gained widespread application and advancement. However, there are still challenging issues, manifesting in two primary facets: firstly, the imaging mechanism of SAR results in significant noise interference, making it difficult to separate background noise from ship target features in complex backgrounds such as ports and urban areas; secondly, the heterogeneous scales of ship target features result in the susceptibility of smaller targets to information loss, rendering them elusive to detection. In this article, we propose a context-aware one-stage ship detection network that exhibits heightened sensitivity to scale variations and robust resistance to noise interference. Then we introduce a Local feature refinement module (LFRM), which utilizes multiple receptive fields of different sizes to extract local multi-scale information, followed by a two-branch channel-wise attention approach to obtain local cross-channel interactions. To minimize the effect of a complex background on the target, we design the global context aggregation module (GCAM) to enhance the feature representation of the target and suppress the interference of noise by acquiring long-range dependencies. Finally, we validate the effectiveness of our method on three publicly available SAR ship detection datasets, SAR-Ship-Dataset, high-resolution SAR images dataset (HRSID), and SAR ship detection dataset (SSDD). The experimental results show that our method is more competitive, with AP50s of 96.3, 93.3, and 96.2% on the three publicly available datasets, respectively.
Disruption of the autism-associated gene SCN2A alters synaptic development and neuronal signaling in patient iPSC-glutamatergic neurons
Authors: Brown Chad O. , Uy Jarryll A. , Murtaza Nadeem , Rosa Elyse , Alfonso Alexandria , Dave Biren M. , Kilpatrick Savannah , Cheng Annie A. , White Sean H. , Scherer Stephen W. , Singh Karun K.
Published: January 2024

SCN2A is an autism spectrum disorder (ASD) risk gene and encodes a voltage-gated sodium channel. However, the impact of ASD-associated SCN2A de novo variants on human neuron development is unknown. We studied SCN2A using isogenic SCN2A–/– induced pluripotent stem cells (iPSCs), and patient-derived iPSCs harboring a de novo R607* truncating variant. We used Neurogenin2 to generate excitatory (glutamatergic) neurons and found that SCN2A+/R607* and SCN2A–/– neurons displayed a reduction in synapse formation and excitatory synaptic activity. We found differential impact on actional potential dynamics and neuronal excitability that reveals a loss-of-function effect of the R607* variant. Our study reveals that a de novo truncating SCN2A variant impairs the development of human neuronal function.
The role of apoptosis in spinal cord injury: a bibliometric analysis from 1994 to 2023
Authors: Wang Siqiao , Cheng Liming
Published: January 2024

Background

Apoptosis after spinal cord injury (SCI) plays a pivotal role in the secondary injury mechanisms, which cause the ultimate neurologic insults. A better understanding of the molecular and cellular basis of apoptosis in SCI allows for improved glial and neuronal survival via the administrations of anti-apoptotic biomarkers. The knowledge structure, development trends, and research hotspots of apoptosis and SCI have not yet been systematically investigated.

Methods

Articles and reviews on apoptosis and SCI, published from 1st January 1994 to 1st Oct 2023, were retrieved from the Web of Science™. Bibliometrix in R was used to evaluate annual publications, countries, affiliations, authors, sources, documents, key words, and hot topics.

Results

A total of 3,359 publications in accordance with the criterions were obtained, which exhibited an ascending trend in annual publications. The most productive countries were the USA and China. Journal of Neurotrauma was the most impactive journal; Wenzhou Medical University was the most prolific affiliation; Cuzzocrea S was the most productive and influential author. “Apoptosis,” “spinal-cord-injury,” “expression,” “activation,” and “functional recovery” were the most frequent key words. Additionally, “transplantation,” “mesenchymal stemness-cells,” “therapies,” “activation,” “regeneration,” “repair,” “autophagy,” “exosomes,” “nlrp3 inflammasome,” “neuroinflammation,” and “knockdown” were the latest emerging key words, which may inform the hottest themes.

Conclusions

Apoptosis after SCI may cause the ultimate neurological damages. Development of novel treatments for secondary SCI mainly depends on a better understanding of apoptosis-related mechanisms in molecular and cellular levels. Such therapeutic interventions involve the application of anti-apoptotic agents, free radical scavengers, as well as anti-inflammatory drugs, which can be targeted to inhibit core events in cellular and molecular injury cascades pathway.
Non-neoplastic astrocytes: key players for brain tumor progression
Authors: Catalano Myriam , Limatola Cristina , Trettel Flavia
Published: January 2024

Astrocytes are highly plastic cells whose activity is essential to maintain the cerebral homeostasis, regulating synaptogenesis and synaptic transmission, vascular and metabolic functions, ions, neuro- and gliotransmitters concentrations. In pathological conditions, astrocytes may undergo transient or long-lasting molecular and functional changes that contribute to disease resolution or exacerbation. In recent years, many studies demonstrated that non-neoplastic astrocytes are key cells of the tumor microenvironment that contribute to the pathogenesis of glioblastoma, the most common primary malignant brain tumor and of secondary metastatic brain tumors. This Mini Review covers the recent development of research on non-neoplastic astrocytes as tumor-modulators. Their double-edged capability to promote cancer progression or to represent potential tools to counteract brain tumors will be discussed.
Neural basis for behavioral plasticity during the parental life-stage transition in mice
Authors: Miyamichi Kazunari
Published: January 2024

Parental care plays a crucial role in the physical and mental well-being of mammalian offspring. Although sexually naïve male mice, as well as certain strains of female mice, display aggression toward pups, they exhibit heightened parental caregiving behaviors as they approach the time of anticipating their offspring. In this Mini Review, I provide a concise overview of the current understanding of distinct limbic neural types and their circuits governing both aggressive and caregiving behaviors toward infant mice. Subsequently, I delve into recent advancements in the understanding of the molecular, cellular, and neural circuit mechanisms that regulate behavioral plasticity during the transition to parenthood, with a specific focus on the sex steroid hormone estrogen and neural hormone oxytocin. Additionally, I explore potential sex-related differences and highlight some critical unanswered questions that warrant further investigation.
The time-evolving epileptic brain network: concepts, definitions, accomplishments, perspectives
Authors: Bröhl Timo , Rings Thorsten , Pukropski Jan , von Wrede Randi , Lehnertz Klaus
Published: January 2024

Epilepsy is now considered a network disease that affects the brain across multiple levels of spatial and temporal scales. The paradigm shift from an epileptic focus—a discrete cortical area from which seizures originate—to a widespread epileptic network—spanning lobes and hemispheres—considerably advanced our understanding of epilepsy and continues to influence both research and clinical treatment of this multi-faceted high-impact neurological disorder. The epileptic network, however, is not static but evolves in time which requires novel approaches for an in-depth characterization. In this review, we discuss conceptual basics of network theory and critically examine state-of-the-art recording techniques and analysis tools used to assess and characterize a time-evolving human epileptic brain network. We give an account on current shortcomings and highlight potential developments towards an improved clinical management of epilepsy.
Decreased phrenic nerve compound muscle action potential, inspiratory muscle strength, and exercise capacity after COVID-19
Authors: Vonbank Karin , Nics Helena , Zwick Ralf Harun , Maasz Julia , Sabic Benjamin , Potzmann Marijan , Brandhofer Georg , Fuchs Julia , Yeghiazaryan Lusine , Burtscher Martin , Paternostro-Sluga Tatjana
Published: January 2024

Objectives

Respiratory muscle weakness with higher ventilatory demands were reported even in patients recovering from only mild COVID-19 symptoms. Aim of this study was to assess the function of phrenic nerve and inspiratory respiratory muscle as well as cardiopulmonary exercise capacity in patients with prolonged exertional dyspnea after COVID-19 infection.

Methods

In this observational exploratory study, electrophysiological examination of the phrenic nerve, inspiratory muscle capacity as well as lung function test, 6-min walk distance (6MWD) and cardiopulmonary exercise test, have been performed in 22 patients post COVID-19 diagnosis (post-CoV).

Results

Exercise capacity (peak workload, Wpeak % predicted and peak oxygen uptake, VO2peak % predicted) were significantly affected in the post-CoV patients (61.8 ± 23.3 Wpeak % and 70.9 ± 22.3 VO2peak %). Maximum inspiratory pressure (MIP) was reduced (60.1 ± 25.5 mbar). In 6 of the 22 patients the electrophysiological response of the phrenic nerve was pathologically decreased (reduced compound muscle action potential, CMAP), while nerve conduction velocity (NCV) was normal, which corresponds to reduced muscle fiber contraction capacity. Positive relationships were demonstrated between 6MWD and MIP (rs = 0.88) as well as quality of life questionnaire (CRQ) and MIP (rs = 0.71) only in patients with reduced CMAP.

Discussion

Respiratory muscle weakness and exercise capacity is associated with reduced phrenic nerve CMAP without signs of neuropathy. This indicates that muscle fiber pathology of the diaphragm may be one pathophysiological factor for the prolonged respiratory symptoms after COVID-19 infections.
Ultrasound-guided stellate ganglion blockade – patient positioning is everything: a case report demonstrating the efficacy of a modified out-of-plane approach
Authors: Mo Ke , Qian Liang , Tian Jingling , Liao Junling , Tan Fang , Kong Weirong , Yu Xianjun , Chi Xinjin
Published: January 2024

Background

Insomnia has become increasingly prevalent in modern society and is notoriously difficult to treat. Many patients exhibit a poor response to pharmacological interventions. Stellate ganglion block (SGB) has emerged as an effective method for managing insomnia; however, its efficacy may be compromised in some patients, primarily due to a variant vertebral artery anatomy.

Case presentation

This case report describes a patient with severe insomnia accompanied by anxiety. Through cervical ultrasound scanning, we identified richly branched cervical arteries at the C6−C7 segment of the vertebral artery, along with anatomical variations, which could pose a heightened risk for the traditional SGB procedure. Therefore, after carefully adjusting the patient’s positioning, we proceeded with ultrasound-guided SGB using a lateral paravein out-of-plane approach. Clinical signs of successful insomnia symptoms alleviation were consistently observed after each block utilizing this alternative technique multiple times in a single patient.

Conclusion

Our report reveals a new lateral paravein out-of-plane approach for ultrasound-guided SGB to treat insomnia, which might be considered an alternative method. More studies should be carried out to confirm the efficacy of this new approach.
An assessment of PET and CMR radiomic features for the detection of cardiac sarcoidosis
Authors: Mushari Nouf A. , Soultanidis Georgios , Duff Lisa , Trivieri Maria G. , Fayad Zahi A. , Robson Philip , Tsoumpas Charalampos
Published: January 2024

Background

Visual interpretation of PET and CMR may fail to identify cardiac sarcoidosis (CS) with high specificity. This study aimed to evaluate the role of [18F]FDG PET and late gadolinium enhancement (LGE)-CMR radiomic features in differentiating CS from another cause of myocardial inflammation, in this case patients with cardiac-related clinical symptoms following COVID-19.

Methods

[18F]FDG PET and LGE-CMR were treated separately in this work. There were 35 post-COVID-19 (PC) and 40 CS datasets. Regions of interest were delineated manually around the entire left ventricle for the PET and LGE-CMR datasets. Radiomic features were then extracted. The ability of individual features to correctly identify image data as CS or PC was tested to predict the clinical classification of CS vs. PC using Mann–Whitney U-tests and logistic regression. Features were retained if the P-value was <0.00053, the AUC was >0.5, and the accuracy was >0.7. After applying the correlation test, uncorrelated features were used as a signature (joint features) to train machine learning classifiers. For LGE-CMR analysis, to further improve the results, different classifiers were used for individual features besides logistic regression, and the results of individual features of each classifier were screened to create a signature that included all features that followed the previously mentioned criteria and used it them as input for machine learning classifiers.

Results

The Mann–Whitney U-tests and logistic regression were trained on individual features to build a collection of features. For [18F]FDG PET analysis, the maximum target-to-background ratio (TBRmax) showed a high area under the curve (AUC) and accuracy with small P-values (<0.00053), but the signature performed better (AUC 0.98 and accuracy 0.91). For LGE-CMR analysis, the Gray Level Dependence Matrix (gldm)-Dependence Non-Uniformity showed good results with small error bars (accuracy 0.75 and AUC 0.87). However, by applying a Support Vector Machine classifier to individual LGE-CMR features and creating a signature, a Random Forest classifier displayed better AUC and accuracy (0.91 and 0.84, respectively).

Conclusion

Using radiomic features may prove useful in identifying individuals with CS. Some features showed promising results in differentiating between PC and CS. By automating the analysis, the patient management process can be accelerated and improved.
Identification of RNAi hypoallergic bread wheat lines for wheat-dependent exercise-induced anaphylaxis patients
Authors: Guzmán-López María H. , Ruipérez Violeta , Marín-Sanz Miriam , Ojeda-Fernández Isabel , Ojeda-Fernández Pedro , Garrote-Adrados José Antonio , Arranz-Sanz Eduardo , Barro Francisco
Published: January 2024

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is one of the most severe forms of wheat allergy. It occurs in patients when they exercise after ingesting wheat-containing foods. Nowadays, the only possible alternative for WDEIA patients is to avoid such foods. This study investigated the potential of six RNA of interference (RNAi) wheat lines with low-prolamin content as alternatives for WDEIA patients. For that purpose, a high performance-liquid chromatography (HPLC) analysis was performed to evaluate differences in gluten protein fractions among these lines. Next, western blots were conducted to measure the immunoglobulin E (IgE) reactivity to wheat proteins in sera from five WDEIA patients. Additionally, monoclonal antibodies (moAb) recognition sites and the IgE binding sites were searched in all peptides identified by LC-MS/MS after protein digestion. The results showed a 61.4%–81.2% reduction in the gliadin content of the RNAi lines, accompanied by an increase in their high-molecular weight (HMW) glutenin content compared to the wild type bread wheat line (WT). In all cases, the reduction in gliadin content correlated with a decrease in IgE reactivity observed in the sera of WDEIA patients, highlighting the E82 and H320 lines. These two RNAi lines exhibited a ≤90% reduction in IgE reactivity. This reduction could be attributed to an absence of IgE binding sites associated with α- and ω5-gliadins, which were present in the WT. Overall, these lines offer a potential alternative for foodstuff for individuals with WDEIA.
Furosemide in pediatric intensive care: a retrospective cohort analysis
Authors: Gaetani Melany , Parshuram Christopher S. , Redelmeier Donald A.
Published: January 2024

Introduction

Furosemide is the most commonly used medication in pediatric intensive care. Growing data indicates improved hemodynamic stability and efficacy of furosemide infusions compared to intermittent injections, thereby suggesting furosemide infusions might be considered as first line therapy in critically ill, paediatric patients. The objective of this study is to examine furosemide treatment as either continuous infusions or intermittent injections and subsequent patient outcomes.

Methods

This is a retrospective cohort analysis of patients treated in a pediatric intensive care unit (ICU) over a nine year period (July 31st 2006 and July 31, 2015). Eligible patients were admitted to either the general pediatric or cardiac specific ICU for a duration of at least 6 hours and who received intravenous furosemide treatment.

Results

A total of 7,478 patients were identified who received a total of 118,438 furosemide administrations for a total of 113,951 (96%) intermittent doses and 4,487 (4%) infusions running for a total of 1,588,750 hours. A total of 5,996 (80%) patients received exclusively furosemide injections and 1,482 (20%) patients received at least one furosemide infusion. A total of 193 patients died during ICU admission, amounting to 87 (6%) of the 1,482 patients who received an infusion and 106 (2%) of the 5,996 who received intermittent injections. Multivariable regression analysis showed no statistically significant decrease in adjusted mortality for patients who received furosemide injections compared to furosemide infusions (aOR 1.20, CI 0.76–1.89).

Discussion

This retrospective study observed similar mortality for patients who received furosemide infusions compared to furosemide injections. More research on furosemide in the ICU could provide insights on fluid management, drug effectiveness, and pharmacologic stewardship for critically ill children.
Development and validation of a nomogram for predicting pulmonary infection in patients receiving immunosuppressive drugs
Authors: Luo Chuxuan , Zhang Yue , Zhang Jiajie , Jin Chen , Ye Xiaolan , Ren Yan , Shen Huajuan , Chen Maosheng , Li Yiwen , He Qiang , Xu Guangbiao , Shao Lina
Published: January 2024

Objective: Pulmonary infection (PI), a severe complication of immunosuppressive therapy, affects patients’ prognosis. As part of this study, we aimed to construct a pulmonary infection prediction (PIP) model and validate it in patients receiving immunosuppressive drugs (ISDs).

Methods: Totally, 7,977 patients being treated with ISDs were randomised 7:3 to the developing (n = 5,583) versus validation datasets (n = 2,394). Our predictive nomogram was established using the least absolute shrinkage and selection operator (LASSO) and multivariate COX regression analyses. With the use of the concordance index (C-index) and calibration curve, the prediction performance of the final model was evaluated.

Results: Among the patients taking immunosuppressive medication, PI was observed in 548 (6.9%). The median time of PI occurrence after immunosuppressive therapy was 123.0 (interquartile range: 63.0, 436.0) days. Thirteen statistically significant independent predictors (sex, age, hypertension, DM, malignant tumour, use of biologics, use of CNIs, use of methylprednisolone at 500 mg, use of methylprednisolone at 40 mg, use of methylprednisolone at 40 mg total dose, use of oral glucocorticoids, albumin level, and haemoglobin level) were screened using the LASSO algorithm and multivariate COX regression analysis. The PIP model built on these features performed reasonably well, with the developing C-index of 0.87 (sensitivity: 85.4%; specificity: 81.0%) and validation C-indices of 0.837, 0.829, 0.832 and 0.830 for predicting 90-, 180-, 270- and 360-day PI probability, respectively. The decision curve analysis (DCA) and calibration curves displayed excellent clinical utility and calibration performance of the nomogram.

Conclusion: The PIP model presented herein could aid in the prediction of PI risk in individual patients who receive immunosuppressive treatment and help personalise clinical decision-making.
Exposure–response analysis using time-to-event data for bevacizumab biosimilar SB8 and the reference bevacizumab
Authors: Park Suemin , Jung Jin Ah , Ju Sungil , Lim Hyeong-Seok
Published: January 2024

Purpose: This analysis aimed to characterize the exposure–response relationship of bevacizumab in non-small-cell lung cancer (NSCLC) and evaluate the efficacy of SB8, a bevacizumab biosimilar, and Avastin®, the reference bevacizumab sourced from the European Union (EU), based on the exposure reported in a comparative phase III efficacy and safety study (EudraCT, 2015-004026-34; NCT 02754882).

Materials and methods: The overall survival (OS) and progression-free survival (PFS) data from 224 patients with steady-state trough concentrations (Css,trough) were analyzed. A parametric time-to-event (TTE) model was developed using NONMEM®, and the effects of treatments (SB8 and bevacizumab-EU) and patient demographic and clinical covariates on OS and PFS were evaluated. Simulations of median OS and PFS by bevacizumab Css,trough were conducted, and concentrations required to achieve 50% and 90% of the maximum median TTE were computed.

Results: A log-logistics model with Css,trough best described the OS and PFS data. Treatment was not a predictor of the hazard for OS or PFS. Simulations revealed steep exposure–response curves with a phase of rapid rise before saturating to a plateau. The median Css,trough values of SB8 and bevacizumab-EU reported from the clinical study were on the plateaus of the exposure–response curves. The concentrations required to achieve 50% and 90% of the maximum effect were 82.4 and 92.2 μg/mL, respectively, for OS and 79.7 and 89.1 μg/mL, respectively, for PFS.

Conclusion: Simulations based on the constructed TTE models for OS and PFS have well described the exposure–response relationship of bevacizumab in advanced NSCLC. The analysis demonstrated comparable efficacy between SB8 and bevacizumab-EU in terms of OS and PFS based on their exposure levels.
The nuclear factor kappa B signaling pathway is a master regulator of renal fibrosis
Authors: Ren Na , Wang Wen-Feng , Zou Liang , Zhao Yan-Long , Miao Hua , Zhao Ying-Yong
Published: January 2024

Renal fibrosis is increasingly recognized as a global public health problem. Acute kidney injury (AKI) and chronic kidney disease (CKD) both result in renal fibrosis. Oxidative stress and inflammation play central roles in progressive renal fibrosis. Oxidative stress and inflammation are closely linked and form a vicious cycle in which oxidative stress induces inflammation through various molecular mechanisms. Ample evidence has indicated that a hyperactive nuclear factor kappa B (NF-ƙB) signaling pathway plays a pivotal role in renal fibrosis. Hyperactive NF-ƙB causes the activation and recruitment of immune cells. Inflammation, in turn, triggers oxidative stress through the production of reactive oxygen species and nitrogen species by activating leukocytes and resident cells. These events mediate organ injury through apoptosis, necrosis, and fibrosis. Therefore, developing a strategy to target the NF-ƙB signaling pathway is important for the effective treatment of renal fibrosis. This Review summarizes the effect of the NF-ƙB signaling pathway on renal fibrosis in the context of AKI and CKD (immunoglobulin A nephropathy, membranous nephropathy, diabetic nephropathy, hypertensive nephropathy, and kidney transplantation). Therapies targeting the NF-ƙB signaling pathway, including natural products, are also discussed. In addition, NF-ƙB-dependent non-coding RNAs are involved in renal inflammation and fibrosis and are crucial targets in the development of effective treatments for kidney disease. This Review provides a clear pathophysiological rationale and specific concept-driven therapeutic strategy for the treatment of renal fibrosis by targeting the NF-ƙB signaling pathway.
Seasonal variations for newly prescribed urate-lowering drugs for asymptomatic hyperuricemia and gout in Japan
Authors: Kurajoh Masafumi , Akari Seigo , Nakamura Takashi , Ihara Yasutaka , Imai Takumi , Morioka Tomoaki , Emoto Masanori
Published: January 2024

Background: Urate-lowering drugs (ULDs) have been approved for treatment of asymptomatic hyperuricemia and gout in Japan. Although serum urate levels and rates of gout onset are known to have seasonal variations, no survey results regarding the seasonality of ULD prescriptions for asymptomatic hyperuricemia and gout have been reported.

Methods: A large-scale database of medical claims in Japan filed between January 2019 and December 2022 was accessed. In addition to total size of the recorded population for each month examined, the numbers of patients every month with newly prescribed ULDs for asymptomatic hyperuricemia and gout were noted, based on the International Classification of Diseases, 10th Revision, codes E79.0 and M10.

Results: The results identified 201,008 patients with newly prescribed ULDs (median age 49.0 years, male 95.6%). Of those, 64.0% were prescribed ULDs for asymptomatic hyperuricemia and 36.0% for gout. The proportion of new ULD prescriptions was seasonal, with that significantly (p < 0.001) higher in summer (June–August) [risk ratio (RR) 1.322, 95% CI 1.218 to 1.436] and autumn (September–November) (RR 1.227, 95% CI 1.129–1.335) than in winter (December–February), whereas the proportion in spring (March–May) was not significantly different from winter. There was no significant difference after stratification by drug type (uric acid production inhibitor/uricosuric agent) or size of the medical institution, nor subgrouping by age or sex (p for interaction = 0.739, 0.727, 0.886, and 0.978, respectively). On the other hand, the proportions of new ULD prescriptions for asymptomatic hyperuricemia were significantly lower and for gout significantly higher in spring than winter, while those were similar in summer and autumn for both groups (p for interaction<0.001).

Conclusion: The present findings indicate that new prescriptions for ULDs to treat asymptomatic hyperuricemia or gout in Japan show seasonal differences, with higher rates noted in summer and autumn as compared to winter.
Evolutionary game analysis of stakeholders’ decision-making behavior in agricultural data supply chain
Authors: Zhao Heyang , Yang Jian
Published: January 2024

The significance of agricultural information sharing in fostering agricultural development cannot be overstated. This practice plays a pivotal role in disseminating cutting-edge agricultural technologies, cultivation methods, and pest control strategies, empowering farmers with valuable knowledge to enhance crop yield and quality. Moreover, it aligns with government objectives of resource sharing and addressing gaps, contributing to the advancement of agricultural modernization and the development of the industry chain. Despite its inherent benefits, the practical implementation of agricultural information sharing faces challenges. Stakeholders engaged in information sharing often prioritize individual benefits, potentially leading to a decline in agricultural information quality and the inefficient use of experimental resources. To confront this issue, the present research establishes a three-party evolutionary game model comprising an agricultural product data sharing platform, agricultural data providers, and agricultural data consumers. Leveraging dynamic system theory, the model analyzes the evolutionary stable strategies of stakeholders and investigates the critical factors influencing the strategic choices of these three parties. Experimental findings underscore the pivotal role of participants’ initial strategies, regulatory intensity, reward and punishment mechanisms, and information feedback in shaping stakeholder decision-making behavior. Implementation of measures such as heightened scrutiny of information on the sharing platform and fostering consumer trust in data emerges as imperative for enhancing system stability. These actions are essential for constructing an efficient and reliable information-sharing ecosystem, thereby facilitating the sustainable development of modern agriculture.
Therapeutic aphorisms for paranoid personality disorder and paranoid ideation treatment: psychological opposites and complementaries in brief therapy
Authors: Paoli Bernardo
Published: January 2024

Background

In brief therapy (BT), aphorisms (As) have been considered a privileged element in therapeutic language. With a handful of words, they arouse emotions and different perspectives.

Theoretical proposal

In As, a specific structure—the implicit and explicit symmetry of opposites (SoO)—allows a surprise effect, which in turn allows a therapeutic effect. Therefore, a carefully selected SoO (based on psychological complementaries) underlies the desired therapeutic reframing, which can be identified as a core goal of the psychotherapeutic intervention.

Research question

Is it possible to identify As with therapeutic value in treating paranoid personality disorder (PPD) and high paranoid ideation (hPI) cases?

Method

Starting from an initial collection of 369 original As created on the spot in 2,335 BT sessions, As used during on-line psychotherapy on 55 patients with PPD and/or an hPI measured with the SCL-90-R were identified.

Results

Thirty-three As were selected and organised according to effective and ineffective strategies, the target of the BT intervention for PPD and hPI cases.
The relationship between sensory processing sensitivity and medication sensitivity: brief report
Authors: Jagiellowicz Jadzia , Acevedo Bianca P. , Tillmann Teresa , Aron Arthur , Aron Elaine N.
Published: January 2024

Sensory processing sensitivity (SPS) is a biological/temperament trait that is associated with greater awareness of and reactivity to the environment, which results in amplified responses to various stimuli, and possibly medications. We investigated the relationship between SPS and medication sensitivity in three studies. Participants (ages 18–81) were recruited from university (Study 1: N = 125; Study 2: N = 214) and online (Study 3: N = 351) samples. In each study, participants completed a medication sensitivity scale, the standard highly sensitive person (HSP) scale to assess SPS, and a negative affectivity (NA) scale as a control variable. All three studies found moderate, significant correlations between SPS and medication sensitivity (r = 0.34, p < 0.001: r = 0.21, p = 0.003; r = 0.36, p < 0.001, respectively). Correlations remained significant, and similar, when controlling for NA and gender; and there were no significant interactions with gender. In sum, our results suggest that SPS is associated with medication sensitivity, even when considering NA and gender. Thus, future work might consider SPS when investigating recommended medication, medication dosage, effectiveness, and adverse drug reactions.
Train to sustain: a randomised controlled trial evaluation of a vitality training employing behaviour-change techniques
Authors: Plant Bernice R. C. , Van Leeuwen Mattheis L. , Peters Pascale , Van der Heijden Beatrice I. J. M.
Published: January 2024

Introduction

This paper reports on the effects of a 9-week vitality training that employed behaviour-change techniques and was evaluated using a randomised controlled trial (RCT) in three large companies based in the Netherlands.

Methods

A total of 84 adult employees from three participating organisations in the Netherlands were enrolled in the study. A parallel group RCT design was employed and participants were assigned using individual random assignment to either an intervention (n = 38) or a waitlist control group (n = 46). The intervention consisted of a 9-week vitality training employing the behaviour-change techniques of self-persuasion, implementation intentions, and self-efficacy, which was delivered in-house over five fortnightly 2-hour sessions. Primary outcomes (i.e., reported energy and stress) and secondary outcomes (i.e., reported daily life satisfaction and work capacity) were assessed prior to, immediately after, and 3 months following the intervention.

Results

A mixed MANOVA revealed a significant interaction effect between treatment group and time period for the combination of reported energy, stress, daily life satisfaction, and work capacity. Subsequent univariate ANOVAs revealed significant interactions between treatment group and time period for reported energy, stress, and daily life satisfaction; however, not for reported work capacity. Improvements in outcomes were observed for both groups following their completion of the vitality training; however, not all improvements reached statistical significance. Reported self-efficacy regarding managing work-life balance was found to mediate the relationship between the effects of the intervention and reported energy; however, such an effect was not found for stress.

Discussion

An intervention drawing upon evidence-based behaviour-change techniques shows promise for improving indicators associated with burnout; although, it is recommended that in future research a larger-scale evaluation be conducted over a longer time period with an active control group to establish effectiveness.

Clinical trial registration:https://www.anzctr.org.au/, ACTRN12622001268730.