bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical analysis of 96 patients with intraorbital foreign bodies: A 10-year retrospective study
Authors: You Yayan , Wang Xinghua , Cheng Shengnan , Zhu Ru , Wang Bowen , Li Shuang , Jiang Fagang
Published: November 2022

Introduction

To investigate the clinical manifestations, diagnosis, and surgical treatment of intraorbital foreign bodies (IOFBs).

Methods

Patients with IOFBs were enrolled from Wuhan Union Hospital between January 2011 and January 2021. Demographic and clinical information was extracted, including gender, age, cause and entrance of the trauma, material, size and quantity of foreign body, visual function, ocular complications, imaging findings, and surgical intervention. The patients were divided into two groups according to the timeline, group A (from January 2011 to December 2015, n = 39) and group B (from January 2016 to January 2021, n = 57).

Results

The 96 patients (81 men and 15 women) were enrolled in this series, with a median age of 39.5 (1.6–76.0) years. Work-related injuries were the cause of IOFBs in 45 individuals (46.9%). Three patients (3.3%) presented severe visual impairment, and 39 patients (42.4%) presented blindness. The majority of foreign bodies were metal (44.8%), followed by wood (26.0%). Computed tomography (CT) and magnetic resonance imaging (MRI) were performed, respectively, on 89 (92.7%) and 21 (21.9%) patients with IOFBs, in which the detection rate was 80.9% for CT and 81.0% for MRI. Among the 25 patients with intraorbital wooden foreign bodies (IOWFBs), the utilization and detection rates of MRI were 50.0% and 40.0% in group A, and 93.3% and 92.9% in group B, with significant differences in both rates between the two groups (both P < 0.05). The IOWFBs detection rate in MRI was significantly higher than that in CT (78.9% vs. 45.8% overall and 92.9% vs. 53.5% in group B). The detection rates of IOFBs and IOWFBs in initial surgery were statistically different between the two groups, of which the rates were 84.6% and 40.0% in group A and 98.2% and 93.3% in group B. The reoperation rate of IOWFBs in group B (20.0%) was significantly lower than that in group A (70.0%).

Conclusion

IOFBs were mainly caused by work-related injuries and might lead to serious visual impairment. The application and detectability of MRI in IOWFBs improved in recent years, and MRI presented better detectability than CT in diagnosing IOWFBs. Thus, MRI should be recommended despite negative CT findings.
Use of 18F-fluorodeoxyglucose positron emission tomography-computed tomography in patients affected by polymyalgia rheumatica and persistent increase of acute phase reactants
Authors: Colaci Michele , Dichiara Jessika , Aprile Maria Letizia , Ippolito Massimo , Schinocca Claudia , Guggino Giuliana , Malatino Lorenzo
Published: November 2022

Polymyalgia rheumatica (PMR) is an inflammatory disease affecting older adults characterized by aching pain and morning stiffness of the shoulder and pelvic girdles. Moreover, PMR can be associated with giant cell arteritis (GCA). Generally, PMR is highly responsive to steroids, reaching complete remission in the majority of cases. However, the possibility of occult diseases, including extra-cranial GCA, should be excluded. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is able to detect the presence of peri-/articular or vascular inflammation, which may be both present in PMR, thus representing a useful diagnostic tool, mainly in presence of extra-cranial GCA. We retrospectively evaluated all consecutive patients who received the diagnosis of PMR in our rheumatology clinic, classified according to the 2012 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria, in the period between April 2020 and May 2022. Among this case series, we selected the patients who underwent 18F-FDG-positron emission tomography (PET) because of the persistent increase of acute phase reactants (APR) besides the steroid therapy. Eighty patients were diagnosed with PMR. Nine out of them also presented arthritis of the wrists during the follow-up, whereas none showed signs of cranial GCA at the diagnosis. Seventeen out of eighty subjects (mean age 71.5 ± 7.5 years; M/F 2/15) presented persistent increase of erythrocyte sedimentation rate (mean ESR 44.2 ± 20.8 mm/h) and/or C-reactive protein (mean CRP 25.1 ± 17 mg/l), thus they underwent total body 18F-FDG-PET/CT. Large vessel 18F-FDG uptake indicating an occult GCA was found in 5/17 (29.4%) cases. Twelve out of seventeen (70.6%) patients showed persistence of peri-/articular inflammation, suggesting a scarce control of PMR or the presence of chronic arthritis. Finally, in 2 cases, other inflammatory disorders were found, namely an acute thyroiditis and a hip prosthesis occult infection. 18F-FDG-PET/CT in PMR patients with persistent increase of APR is a useful diagnostic technique in order to detect occult GCA, persistence of active PMR or other misdiagnosed inflammatory diseases.
Closed–loop oxygen control improves oxygenation in pediatric patients under high–flow nasal oxygen—A randomized crossover study
Authors: Sandal Ozlem , Ceylan Gokhan , Topal Sevgi , Hepduman Pinar , Colak Mustafa , Novotni Dominik , Soydan Ekin , Karaarslan Utku , Atakul Gulhan , Schultz Marcus J. , Ağın Hasan
Published: November 2022

Background

We assessed the effect of a closed–loop oxygen control system in pediatric patients receiving high–flow nasal oxygen therapy (HFNO).

Methods

A multicentre, single–blinded, randomized, and cross–over study. Patients aged between 1 month and 18 years of age receiving HFNO for acute hypoxemic respiratory failure (AHRF) were randomly assigned to start with a 2–h period of closed–loop oxygen control or a 2–h period of manual oxygen titrations, after which the patient switched to the alternative therapy. The endpoints were the percentage of time spent in predefined SpO2ranges (primary), FiO2, SpO2/FiO2, and the number of manual adjustments.

Findings

We included 23 patients, aged a median of 18 (3–26) months. Patients spent more time in a predefined optimal SpO2range when the closed–loop oxygen controller was activated compared to manual oxygen titrations [91⋅3% (IQR 78⋅4–95⋅1%) vs. 63⋅0% (IQR 44⋅4–70⋅7%)], mean difference [28⋅2% (95%–CI 20⋅6–37⋅8%);P< 0.001]. Median FiO2was lower [33⋅3% (IQR 26⋅6–44⋅6%) vs. 42⋅6% (IQR 33⋅6–49⋅9%);P= 0.07], but median SpO2/FiO2was higher [289 (IQR 207–348) vs. 194 (IQR 98–317);P= 0.023] with closed–loop oxygen control. The median number of manual adjustments was lower with closed–loop oxygen control [0⋅0 (IQR 0⋅0–0⋅0) vs. 0⋅5 (IQR 0⋅0–1⋅0);P< 0.001].

Conclusion

Closed-loop oxygen control improves oxygenation therapy in pediatric patients receiving HFNO for AHRF and potentially leads to more efficient oxygen use. It reduces the number of manual adjustments, which may translate into decreased workloads of healthcare providers.

Clinical trial registration

[www.ClinicalTrials.gov], identifier [NCT 05032365].
Multi-view SoftPool attention convolutional networks for 3D model classification
Authors: Wang Wenju , Wang Xiaolin , Chen Gang , Zhou Haoran
Published: November 2022

Introduction

Existing multi-view-based 3D model classification methods have the problems of insufficient view refinement feature extraction and poor generalization ability of the network model, which makes it difficult to further improve the classification accuracy. To this end, this paper proposes a multi-view SoftPool attention convolutional network for 3D model classification tasks.

Methods

This method extracts multi-view features through ResNest and adaptive pooling modules, and the extracted features can better represent 3D models. Then, the results of the multi-view feature extraction processed using SoftPool are used as the Query for the self-attentive calculation, which enables the subsequent refinement extraction. We then input the attention scores calculated by Query and Key in the self-attention calculation into the mobile inverted bottleneck convolution, which effectively improves the generalization of the network model. Based on our proposed method, a compact 3D global descriptor is finally generated, achieving a high-accuracy 3D model classification performance.

Results

Experimental results showed that our method achieves 96.96% OA and 95.68% AA on ModelNet40 and 98.57% OA and 98.42% AA on ModelNet10.

Discussion

Compared with a multitude of popular methods, our algorithm model achieves the state-of-the-art classification accuracy.
Self-assessment of cochlear health by cochlear implant recipients
Authors: Mushtaq Faizah , Soulby Andrew , Boyle Patrick , Nunn Terry , Hartley Douglas E. H.
Published: November 2022

Recent technological advances in cochlear implant (CI) telemetry have enabled, for the first time, CI users to perform cochlear health (CH) measurements through self-assessment for prolonged periods of time. This is important to better understand the influence of CH on CI outcomes, and to assess the safety and efficacy of future novel treatments for deafness that will be administered as adjunctive therapies to cochlear implantation. We evaluated the feasibility of using a CI to assess CH and examined patterns of electrode impedances, electrically-evoked compound action potentials (eCAPs) and electrocochleography (ECochGs), over time, in a group of adult CI recipients. Fifteen subjects were trained to use the Active Insertion Monitoring tablet by Advanced Bionics, at home for 12 weeks to independently record impedances twice daily, eCAPs once weekly and ECochGs daily in the first week, and weekly thereafter. Participants also completed behavioral hearing and speech assessments. Group level measurement compliance was 98.9% for impedances, 100% for eCAPs and 99.6% for ECochGs. Electrode impedances remained stable over time, with only minimal variation observed. Morning impedances were significantly higher than evening measurements, and impedances increased toward the base of the cochlea. eCAP thresholds were also highly repeatable, with all subjects showing 100% measurement consistency at, at least one electrode. Just over half of all subjects showed consistently absent thresholds at one or more electrodes, potentially suggesting the existence of cochlear dead regions. All subjects met UK NICE guidelines for cochlear implantation, so were expected to have little residual hearing. ECochG thresholds were, unsurprisingly, highly erratic and did not correlate with audiometric thresholds, though lower ECochG thresholds showed more repeatability over time than higher thresholds. We conclude that it is feasible for CI users to independently record CH measurements using their CI, and electrode impedances and eCAPs are promising measurements for objectively assessing CH.
Alteration of gut microbiota in migraine patients with irritable bowel syndrome in a Chinese Han population
Authors: Liu Jieqiong , Tang Wenjing , Hou Lei , Wang Jing , Wang Rongfei , Zhang Yaofen , Dong Zhao , Liu Ruozhuo , Yu Shengyuan
Published: November 2022

Objective

Migraine is frequently reported in patients with irritable bowel syndrome (IBS), and emerging evidence suggests that gut microbiota plays a role in migraine and IBS. However, alterations in the gut microbiome in migraine patients with IBS remain unknown. This study aimed to explore the compositions of gut microbiota in migraine patients with IBS in a Chinese Han population.

Methods

Sixteen migraine patients with IBS and thirteen age- and gender-matched IBS patients with similar dietary and lifestyle habits were enrolled in this pilot study. Demographic data, clinical data, eating habits, lifestyle habits, comorbidities, and medications were recorded using a unified case registration form. Questionnaires for the Migraine Disability Assessment (MIDAS), Pittsburgh Sleep Quality Index (PSQI), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD) were completed. Fecal samples were collected, and microbial DNA was extracted. Gut microbiota 16S ribosomal RNA (16S rRNA) gene sequencing targeting the V4 region was performed using the Illumina HiSeq 2500 high-throughput sequencing platform. The relationships between gut microbiota and clinical characteristics of migraine were analyzed.

Results

The structure of gut microbiota differed between migraine patients with IBS and patients with IBS, while the richness and diversity of gut microbiota in migraine patients with IBS showed no significant difference from that of patients with IBS. We found a higher relative abundance of the genus Parabacteroides and a lower relative abundance of the genera Paraprevotella, Lachnospiraceae_UCG-010, Lactococcus, Collinsella, and Comamonas in migraine patients with IBS than in patients with IBS. According to random forest predictive models, the phylum Bacteroidota shows the most important role in migraine patients with IBS. Furthermore, no statistical correlation was found between significantly different taxa at the genus level and migraine clinical data.

Conclusion

This study identified that altered gut microbiota occurred in Chinese Han migraine patients with IBS, but no correlation was found between gut microbiota and the clinical characteristics of migraine. Further study is needed to better understand the role of gut microbiota in the pathogenesis of migraine in IBS.
Toward learning robust contrastive embeddings for binaural sound source localization
Authors: Tang Duowei , Taseska Maja , van Waterschoot Toon
Published: November 2022

Recent deep neural network based methods provide accurate binaural source localization performance. These data-driven models map measured binaural cues directly to source locations hence their performance highly depend on the training data distribution. In this paper, we propose a parametric embedding that maps the binaural cues to a low-dimensional space where localization can be done with a nearest-neighbor regression. We implement the embedding using a neural network, optimized to map points that are close to each other in the latent space (the space of source azimuths or elevations) to nearby points in the embedding space, thus the Euclidean distances between the embeddings reflect their source proximities, and the structure of the embeddings forms a manifold, which provides interpretability to the embeddings. We show that the proposed embedding generalizes well in various acoustic conditions (with reverberation) different from those encountered during training, and provides better performance than unsupervised embeddings previously used for binaural localization. In addition, the proposed method performs better than or equally well as a feed-forward neural network based model that directly estimates the source locations from the binaural cues, and it has better results than the feed-forward model when a small amount of training data is used. Moreover, we also compare the proposed embedding using both supervised and weakly supervised learning, and show that in both conditions, the resulting embeddings perform similarly well, but the weakly supervised embedding allows to estimate source azimuth and elevation simultaneously.
Clinical safety and possible efficacy of tirofiban in combination with intravenous thrombolysis by recombinant tissue plasminogen activator for early treatment of capsular warning syndrome (CWS)
Authors: Liu Yunzhu , Li Shiyong , Hao Dongdong , Zhang Zhongping , Yi Yongxin , Fang Jiayang , Lin Weizhi , Zhang Min
Published: November 2022

The purpose of this study was to assess the efficacy and safety of the combination of tirofiban with intravenous thrombolysis (IVT) in treating patients with capsular warning syndrome (CWS) who failed to respond to the treatment of intravenous thrombolysis alone. Tirofiban was approved for the treatment of CWS patients with fluctuating symptoms or no substantial improvement after intravenous thrombolysis within 24 h in our hospital from October 2019 to June 2021. Patients were evaluated with the National Institutes of Health Stroke Scale (NIHSS) at admission, at 72 h post-thrombolysis, at 1-week, and at 3-months with the modified Rankin Scales (MRS) score. A total of 12 patients received tirofiban and eight patients received control treatment with a history of CWS in our cohort. Among the patients, 13 patients smoked more than one pack of cigarettes a day, 17 had hypertension, 17 had hypercholesterolemia, 7 had diabetes, 1 had the history of cerebral infarction, 2 had atrial fibrillation, 7 had mild big vascular stenosis, 13 had lesions of the perforating branch by imaging, and 19 had acute capsular infarction. In both the tirofiban and control groups, NIHSS scores were significantly reduced after intravenous thrombolysis or 1-week after onset compared with before intravenous thrombolysis (P < 0.001). Before and after intravenous thrombolysis, there were no differences between the tirofiban group and control group (P = 0.970, P = 0.384, respectively). The tirofiban group, however, showed remarkably lower scores in both 1-week NIHSS and 3-month MRS than the control (P = 0.012, P = 0.003, respectively). Our study revealed that tirofiban did not increase the risk of hemorrhage and had favorable clinical efficacy as a remedial treatment for CWS patients with poor prognosis for intravenous thrombolysis, therefore indicating great potential for broader use.
Function of brain-derived neurotrophic factor in the hypothalamus: Implications for depression pathology
Authors: Autry Anita E.
Published: November 2022

Depression is a prevalent mental health disorder and is the number one cause of disability worldwide. Risk factors for depression include genetic predisposition and stressful life events, and depression is twice as prevalent in women compared to men. Both clinical and preclinical research have implicated a critical role for brain-derived neurotrophic factor (BDNF) signaling in depression pathology as well as therapeutics. A preponderance of this research has focused on the role of BDNF and its primary receptor tropomyosin-related kinase B (TrkB) in the cortex and hippocampus. However, much of the symptomatology for depression is consistent with disruptions in functions of the hypothalamus including changes in weight, activity levels, responses to stress, and sociability. Here, we review evidence for the role of BDNF and TrkB signaling in the regions of the hypothalamus and their role in these autonomic and behavioral functions associated with depression. In addition, we identify areas for further research. Understanding the role of BDNF signaling in the hypothalamus will lead to valuable insights for sex- and stress-dependent neurobiological underpinnings of depression pathology.
Food preservation by cold plasma from dielectric barrier discharges in agri-food industries
Authors: Jiang Hao , Lin Qian , Shi Wenqing , Yu Xiuzhu , Wang Shaojin
Published: November 2022

Background

Cold plasma (CP) can be defined as partially or wholly ionized gas carrying myriads of highly reactive products, such as electrons, negative ions, positive ions, free radicals, excited or non-excited atoms, and photons at ambient temperature. It is generated at 30–60°C under atmospheric or reduced pressure (vacuum). In contrast to thermal plasma, it requires less power, exhibits electron temperatures much higher than the corresponding gas (macroscopic temperature), and does not present a local thermodynamic equilibrium. Dielectric barrier discharges (DBD) are one of the most convenient and efficient methods to produce CP.

Scope and approach

Cold plasma technology has the potential to replace traditional agri-food processing purification methods because of its low energy requirements and flexible system design. CP technology works by reducing bacteria levels and removing pests and mycotoxins from your produce at harvest. It can also catalyze physiological and biochemical reactions and modify materials. It can meet microbial food safety standards, improve the physical, nutritional, and sensory characteristics of the products, preserve unstable bioactive compounds, and modulate enzyme activities. This manuscript also discusses the quality characteristics of food components before/after CP treatment.

Key findings and conclusion

In the past decade, CP treatments of food products have experienced increased popularity due to their potential contributions to non-thermal food processing. There is no doubt that CP treatment is a flexible approach with demonstrated efficacy for controlling many risks across food and agricultural sustainability sectors. In addition, CP technologies also can be applied in food-related areas, including modification of chemical structures and desensitization treatments. There is a need to fully assess the benefits and risks of stand-alone CP unit processes or their integration as a processing chain as soon as the economic, ecological, and consumer benefits and acceptability are considered.
Impact of L-ornithine L-aspartate on non-alcoholic steatohepatitis-associated hyperammonemia and muscle alterations
Authors: Pichon Camille , Nachit Maxime , Gillard Justine , Vande Velde Greetje , Lanthier Nicolas , Leclercq Isabelle A.
Published: November 2022

Background

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic liver disease in the world. Progression toward non-alcoholic steatohepatitis (NASH) is associated with alterations of skeletal muscle. One plausible mechanism for altered muscle compartment in liver disease is changes in ammonia metabolism. In the present study, we explored the hypothesis that NASH-associated hyperammonemia drives muscle changes as well as liver disease progression.

Materials and methods

In Alms1-mutant mice (foz/foz) fed a 60% fat diet (HFD) for 12 weeks; we investigated hepatic and muscular ammonia detoxification efficiency. We then tested the effect of an 8 week-long supplementation with L-ornithine L-aspartate (LOLA), a known ammonia-lowering treatment, given after either 4 or 12 weeks of HFD for a preventive or a curative intervention, respectively. We monitored body composition, liver and muscle state by micro computed tomography (micro-CT) as well as muscle strength by four-limb grip test.

Results

According to previous studies, 12 weeks of HFD induced NASH in all foz/foz mice. Increase of hepatic ammonia production and alterations of urea cycle efficiency were observed, leading to hyperammonemia. Concomitantly mice developed marked myosteatosis. First signs of myopenia occurred after 20 weeks of diet. Early LOLA treatment given during NASH development, but not its administration in a curative regimen, efficiently prevented myosteatosis and muscle quality, but barely impacted liver disease or, surprisingly, ammonia detoxification.

Conclusion

Our study confirms the perturbation of hepatic ammonia detoxification pathways in NASH. Results from the interventional experiments suggest a direct beneficial impact of LOLA on skeletal muscle during NASH development, though it does not improve ammonia metabolism or liver disease.
Quantifying 6D tumor motion and calculating PTV margins during liver stereotactic radiotherapy with fiducial tracking
Authors: Sun Xingru , Dai Zhitao , Xu Meiling , Guo Xueling , Su Huanfan , Li Yang
Published: November 2022

Objective

Our study aims to estimate intra-fraction six-dimensional (6D) tumor motion with rotational correction and the related correlations between motions of different degrees of freedom (DoF), as well as quantify sufficient anisotropic clinical target volume (CTV) to planning target volume (PTV) margins during stereotactic body radiotherapy (SBRT) of liver cancer with fiducial tracking technique.

Methods

A cohort of 12 patients who were implanted with 3 or 4 golden markers were included in this study, and 495 orthogonal kilovoltage (kV) pairs of images acquired during the first fraction were used to extract the spacial position of each golden marker. Translational and rotational motions of tumor were calculated based on the marker coordinates by using an iterative closest point (ICP) algorithm. Moreover, the Pearson product-moment correlation coefficients (r) were applied to quantify the correlations between motions with different degrees of freedom (DoFs). The population mean displacement (MP¯), systematic error (Σ) and random error (σ) were obtained to calculate PTV margins based on published recipes.

Results

The mean translational variability of tumors were 0.56, 1.24 and 3.38 mm in the left-right (LR, X), anterior-posterior (AP, Y), and superior-inferior (SI, Z) directions, respectively. The average rotational angles θX , θY and θZ around the three coordinate axes were 0.88, 1.24 and 1.12, respectively. (|r|>0.4) was obtainted between Y -Z , Y - θZ , Z -θZ and θX - θY . The PTV margins calculated based on 13 published recipes in X, Y, and Z directions were 1.08, 2.26 and 5.42 mm, and the 95% confidence interval (CI) of them were (0.88,1.28), (1.99,2.53) and (4.78,6.05), respectively.

Conclusions

The maximum translational motion was in SI direction, and the largest correlation coefficient of Y-Z was obtained. We recommend margins of 2, 3 and 7 mm in LR, AP and SI directions, respectively.
Squamous–columnar junction of Von Ebner’s glands may be a significant origin of squamous cell carcinomas in the base of the tongue
Authors: Chen Peng-Ning , Chen Xin-Yu , Chen Guan-Xi , Luo Lin , Yan Qi-Zhang , Ruan Ping , Li Ping , Yu Da-Hai
Published: November 2022

Objectives

The histological origin of base of the tongue (BOT) carcinomas is still elusive, and most studies have been focusing on the lingual tonsil. In this study, we sought to identify the existence of the squamous–columnar junction (SCJ) in the human Von Ebner’s glandular duct and explored the potential of that in forming squamous cell carcinomas in BOT.

Materials and methods

The specific genomes of BOT carcinoma were acquired and screened out by The Cancer Genome Atlas (TCGA) database analysis. The 4-nitroquinoline-1-oxide (4-NQO)-treated mouse model was used to explore the transformation of SCJ during cancerization. We used immunohistochemistry to confirm the characteristics of SCJ in human Von Ebner’s gland, which were further compared with those in the anus and cervix.

Results

The SCJ in the human Von Ebner’s glandular duct was found to be similar to that of the cervix and anus. The transformation zone in the 4-NQO-treated mouse model had a multilayered epithelium structure similar to that of HPV16-transgenic mice. In human, the transformation zone of Von Ebner’s gland is also similar to that of the cervix and anus.

Conclusion

It is the first time that the existence of SCJ in the opening of the human Von Ebner’s glandular duct was confirmed. The SCJ of Von Ebner’s glands may be a significant origin of squamous cell carcinomas in BOT.
A chronicle review of new techniques that facilitate the understanding and development of optimal individualized therapeutic strategies for chordoma
Authors: Zhao Chenglong , Tan Tao , Zhang E. , Wang Ting , Gong Haiyi , Jia Qi , Liu Tielong , Yang Xinghai , Zhao Jian , Wu Zhipeng , Wei Haifeng , Xiao Jianru , Yang Cheng
Published: November 2022

Chordoma is a rare malignant bone tumor that mainly occurs in the sacrum and the clivus/skull base. Surgical resection is the treatment of choice for chordoma, but the local recurrence rate is high with unsatisfactory prognosis. Compared with other common tumors, there is not much research and individualized treatment for chordoma, partly due to the rarity of the disease and the lack of appropriate disease models, which delay the discovery of therapeutic strategies. Recent advances in modern techniques have enabled gaining a better understanding of a number of rare diseases, including chordoma. Since the beginning of the 21st century, various chordoma cell lines and animal models have been reported, which have partially revealed the intrinsic mechanisms of tumor initiation and progression with the use of next-generation sequencing (NGS) techniques. In this study, we performed a systematic overview of the chordoma models and related sequencing studies in a chronological manner, from the first patient-derived chordoma cell line (U-CH1) to diverse preclinical models such as the patient-derived organoid-based xenograft (PDX) and patient-derived organoid (PDO) models. The use of modern sequencing techniques has discovered mutations and expression signatures that are considered potential treatment targets, such as the expression of Brachyury and overactivated receptor tyrosine kinases (RTKs). Moreover, computational and bioinformatics techniques have made drug repositioning/repurposing and individualized high-throughput drug screening available. These advantages facilitate the research and development of comprehensive and personalized treatment strategies for indicated patients and will dramatically improve their prognoses in the near feature.
Cross-reactivity between histone demethylase inhibitor valproic acid and DNA methylation in glioblastoma cell lines
Authors: Barciszewska Anna-Maria , Belter Agnieszka , Gawrońska Iwona , Giel-Pietraszuk Małgorzata , Naskręt-Barciszewska Mirosława Z.
Published: November 2022

Currently, valproic acid (VPA) is known as an inhibitor of histone deacetylase (epigenetic drug) and is used for the clinical treatment of epileptic events in the course of glioblastoma multiforme (GBM). Which improves the clinical outcome of those patients. We analyzed the level of 5-methylcytosine, a DNA epigenetic modulator, and 8-oxodeoxyguanosine, an cellular oxidative damage marker, affected with VPA administration, alone and in combination with temozolomide (TMZ), of glioma (T98G, U118, U138), other cancer (HeLa), and normal (HaCaT) cell lines. We observed the VPA dose-dependent changes in the total DNA methylation in neoplastic cell lines and the lack of such an effect in a normal cell line. VPA at high concentrations (250-500 μM) induced hypermethylation of DNA in a short time frame. However, the exposition of GBM cells to the combination of VPA and TMZ resulted in DNA hypomethylation. At the same time, we observed an increase of genomic 8-oxo-dG, which as a hydroxyl radical reaction product with guanosine residue in DNA suggests a red-ox imbalance in the cancer cells and radical damage of DNA. Our data show that VPA as an HDAC inhibitor does not induce changes only in histone acetylation, but also changes in the state of DNA modification. It shows cross-reactivity between chromatin remodeling due to histone acetylation and DNA methylation. Finally, total DNA cytosine methylation and guanosine oxidation changes in glioma cell lines under VPA treatment suggest a new epigenetic mechanism of that drug action.
Icotinib derivatives as tyrosine kinase inhibitors with anti-esophageal squamous carcinoma activity
Authors: Chen Xiaojie , Mao Long-Fei , Tian Siqi , Tian Xueli , Meng Xueqiong , Wang Mu-Kuo , Xu Weifeng , Li Yue-Ming , Liu Kangdong , Dong Zigang
Published: November 2022

Previous report showed that a variety of icotinib derivatives bearing different 1,2,3-triazole moieties, which could be readily prepared via copper (I)-catalyzed cycloaddition (CuAAC) reaction between icotinib and different azides, exhibited interesting activity against different lung cancer cell lines such as H460, H1975, H1299, A549 or PC-9. To further expand the application scope of the compounds and to validate the function of triazole groups in drug design, the anti-cancer activity of these compounds against esophageal squamous carcinoma (ESCC) cells was tested herein. Preliminary MTT experiments suggested that these compounds were active against different ESCC cell lines such as KYSE70, KYSE410, or KYSE450 as well as their drug-resistant ones. Especially, compound 3l showed interesting anticancer activity against these cell lines. The mode of action was studied via molecular docking, SPR experiments and other biochemical studies, and 3l exhibited higher binding potential to wild-type EGFR than icotinib did. In vivo anticancer study showed that 3l could inhibit tumor growth of cell-line-derived xenografts in ESCC. Study also suggested that 3l was a potent inhibitor for EGFR-TK pathway. Combining these results, 3l represents a promising lead compound for the design of anti-cancer drugs against ESCC.
A state-of-the-art review of tamoxifen as a potential therapeutic for duchenne muscular dystrophy
Authors: Botti Valeria , Menzel Olivier , Staedler Davide
Published: November 2022

Introduction: This systematic review analyzes the state-of-art repurposing of the drug tamoxifen (TAM) in the treatment of Duchenne Muscular Dystrophy (DMD), including its mechanism of action, toxicological findings, and past and ongoing clinical trials. A parallel aim of this work was to explore whether evidence exists to support further funding of investigation on TAM treatment for DMD patients with a pivotal trial in young patients. Bringing evidence and answering the scientific question of whether this treatment could improve the quality-of-life of DMD patients is needed to establish guidelines and accelerate access to promising therapies for DMD patients.

Methods: The search was conducted in January 2022 utilizing PubMed. All MeSH terms for “Duchenne Muscular Dystrophy” and “tamoxifen” were used. The inclusion and exclusion criteria were defined according to the PICOS framework.

Results: The included publications all explored the use of TAM with promising outcomes in muscular strength recovery and a decrease in pathology biomarkers. Two reviews recognize TAM as a potential treatment for DMD patients and state that drug repurposing plays a crucial role in the quest for a drug candidate to treat this rare disease.

Conclusion: According to available data, TAM shows promise as a treatment for DMD, both pharmacologically and clinically. However, published data to date are insufficient to definitively conclude the beneficial effect of TAM on quality-of-life and ultimately survival, particularly in the youngest patients diagnosed with DMD.
Activation of EP4 alleviates AKI-to-CKD transition through inducing CPT2-mediated lipophagy in renal macrophages
Authors: Guan Xu , Liu Yong , Xin Wang , Qin Shaozong , Gong Shuiqin , Xiao Tangli , Zhang Daohai , Li Yan , Xiong Jiachuan , Yang Ke , He Ting , Zhao Jinghong , Huang Yinghui
Published: November 2022

Acute kidney injury (AKI) is a common clinical syndrome with complex pathogenesis, characterized by a rapid decline in kidney function in the short term. Worse still, the incomplete recovery from AKI increases the risk of progression to chronic kidney disease (CKD). However, the pathogenesis and underlying mechanism remain largely unknown. Macrophages play an important role during kidney injury and tissue repair, but its role in AKI-to-CKD transition remains elusive. Herein, single nucleus RNA sequencing (snRNA-Seq) and flow cytometry validations showed that E-type prostaglandin receptor 4 (EP4) was selectively activated in renal macrophages, rather than proximal tubules, in ischemia-reperfusion injury (IRI)-induced AKI-to-CKD transition mouse model. EP4 inhibition aggravated AKI-to-CKD transition, while EP4 activation impeded the progression of AKI to CKD though regulating macrophage polarization. Mechanistically, network pharmacological analysis and subsequent experimental verifications revealed that the activated EP4 inhibited macrophage polarization through inducing Carnitine palmitoyltransferase 2 (CPT2)-mediated lipophagy in macrophages. Further, CPT2 inhibition abrogated the protective effect of EP4 on AKI-to-CKD transition. Taken together, our findings demonstrate that EP4-CPT2 signaling-mediated lipophagy in macrophages plays a pivotal role in the transition of AKI to CKD and targeting EP4-CPT2 axis could serve as a promising therapeutic approach for retarding AKI and its progression to CKD.
Xuebijing injection inhibited neutrophil extracellular traps to reverse lung injury in sepsis mice via reducing Gasdermin D
Authors: Shang Ting , Zhang Zhi-Sen , Wang Xin-Tong , Chang Jing , Zhou Meng-En , Lyu Ming , He Shuang , Yang Jian , Chang Yan-Xu , Wang Yuefei , Li Ming-Chun , Gao Xiumei , Zhu Yan , Feng Yuxin
Published: November 2022

The mortality of sepsis and septic shock remains high worldwide. Neutrophil extracellular traps (NETs) release is a major cause of organ failure and mortality in sepsis. Targeting Gasdermin D (GSDMD) can restrain NETs formation, which is promising for sepsis management. However, no medicine is identified without severe safety concerns for this purpose. Xuebijing injection (XBJ) has been demonstrated to alleviate the clinical symptoms of COVID-19 and sepsis patients, but there are not enough animal studies to reveal its mechanisms in depth. Therefore, we wondered whether XBJ relieved pulmonary damage in sepsis by suppressing NETs formation and adopted a clinically relevant polymicrobial infection model to test this hypothesis. Firstly, XBJ effectively reversed lung injury caused by sepsis and restrained neutrophils recruitment to lung by down-regulating proinflammatory chemokines, such as CSF-3, CXCL-2, and CXCR-2. Strikingly, we found that XBJ significantly reduced the expressions of NETs component proteins, including citrullinated histone H3 (CitH3), myeloperoxidase (MPO), and neutrophil elastase (NE). GSDMD contributes to the production of NETs in sepsis. Notably, XBJ exhibited a reduced effect on the expressions of GSDMD and its upstream regulators. Besides, we also revealed that XBJ reversed NETs formation by inhibiting the expressions of GSDMD-related genes. Collectively, we demonstrated XBJ protected against sepsis-induced lung injury by reversing GSDMD-related pathway to inhibit NETs formation.
Primary percutaneous coronary intervention in CAD patients: A comparison of major adverse cardiovascular events of second- and third-generation drug-eluting stents
Authors: Bibi Salma , Khan Amjad , Khan Amer Hayat , Khan Muhammad Niaz , Mushtaq Saima , Rashid Sheikh Abdur
Published: November 2022

Background: Biodegradable polymer (BP) drug-eluting stents (DES) have been introduced as a novel solution to the problems of durable polymer (DP) stents. In Pakistan, very few studies are available for the treatment intervention in post-primary percutaneous coronary intervention (PPCI) patients. Our study will compare the major adverse cardiovascular events (MACEs) and their predictors in patients with coronary artery disease (CAD) undergoing PPCI with second- or third-generation DES.

Methodology: An observational, retrospective, cohort study was carried out on CAD patients undergoing PPCI with either second- (DP-XIENCE Prime/XIENCE Xpedition) or third-generation (BP-BioMatrix NeoFlex/BioMatrix Alpha) DES. MACEs were assessed after 1 year of PPCI procedure in 341 patients and screened as per inclusion/exclusion criteria (167 in the second-generation group and 174 in the third-generation group).

Results: The number of male patients (86.2%) was more than female patients in our study population. MACEs were reported in 4.19% patients after 1 year duration, and the percentage of MACEs was more in the second-generation DES group (4.77%) than in the third-generation group (3.44%); however, statistical analysis has not found any significant difference (p = 0.534). The rate of myocardial infarction (1.19% vs. 0.57%) and stent thrombosis (1.8% vs. 1.15%) was more in the second-generation DES group. However, restenosis (1.19% vs. 1.15%) and cardiac death (0.59% vs. 0.57%) were almost same in both groups. A significant association was found between MACEs and diabetes mellitus (p = 0.025), hypertension (p = 0.035), smoking (p = 0.008), and a family history of CAD (p = 0.018).

Conclusion: BP-BioMatrix and DP-XIENCE DES have comparable clinical outcomes. Findings of the current study will assist the policy makers and healthcare providers in the rationalization of scarce resources and evidence-based patient care. However, longer follow-up studies are required for convincing results.
Thermodynamics of the pseudogap in cuprates
Authors: Tallon Jeffery L. , Storey James G.
Published: November 2022

The key thermodynamic characteristics of the pseudogap state in cuprate superconductors are reviewed. These include YBa2Cu3O7−δ, Y0.8Ca0.2Ba2Cu3O7−δ, YBa2Cu4O8, Bi2Sr2CaCu2O8+δ, La2−xSrxCuO4, and Tl2Ba2CuO4. The electronic specific heat was extracted using a differential technique, and the evolution of the specific-heat coefficient γ and electronic entropy S as a function of temperature, doping, and magnetic field reveals a canonical behavior summarized by the following. The normal-state gap which opens in the pseudogap domain apparently remains open to the highest temperatures investigated. The gap decreases in magnitude with increasing doping and closes abruptly at a critical doping of p ≈ 0.19 holes/Cu, independent of temperature. In this picture, the pseudogap is separated from the pseudogap-free region of the phase diagram by a vertical line similar to the vertical line separating the incoherent and coherent antinodal quasiparticle states found in ARPES. The important role of fluctuations is evident by a diverging enhancement of γ(T) on either side of Tc, and this enables extraction of the mean-field transition temperature Tcmf>Tc, defining a crescent of parapairing above Tc(p) which extends across the entire superconducting phase diagram and which is quite distinct from pseudogap phenomenology. The data are consistent with d-wave pairing and the BCS ratios are extracted, revealing canonical near-weak-coupling behavior across the over-doped region with a sudden suppression occurring at p ≈ 0.19 when the pseudogap sets in.
Surface texturing and combinatorial approaches to improve biocompatibility of implanted biomaterials
Authors: Xu Li-Chong , Siedlecki Christopher A.
Published: November 2022

Biomaterial associated microbial infection and blood thrombosis are two of the barriers that inhibit the successful use of implantable medical devices in modern healthcare. Modification of surface topography is a promising approach to combat microbial infection and thrombosis without altering bulk material properties necessary for device function and without contributing to bacterial antibiotic resistance. Similarly, the use of other antimicrobial techniques such as grafting poly (ethylene glycol) (PEG) and nitric oxide (NO) release also improve the biocompatibility of biomaterials. In this review, we discuss the development of surface texturing techniques utilizing ordered submicron-size pillars for controlling bacterial adhesion and biofilm formation, and we present combinatorial approaches utilizing surface texturing in combination with poly (ethylene glycol) (PEG) grafting and NO release to improve the biocompatibility of biomaterials. The manuscript also discusses efforts towards understanding the molecular mechanisms of bacterial adhesion responses to the surface texturing and NO releasing biomaterials, focusing on experimental aspects of the approach.
In silico assessment of pharmacotherapy for carbon monoxide induced arrhythmias in healthy and failing human hearts
Authors: Jiang Huasen , Zhang Shugang , Lu Weigang , Yang Fei , Bi Xiangpeng , Ma Wenjian , Wei Zhiqiang
Published: November 2022

Background: Carbon monoxide (CO) is gaining increased attention in air pollution-induced arrhythmias. The severe cardiotoxic consequences of CO urgently require effective pharmacotherapy to treat it. However, existing evidence demonstrates that CO can induce arrhythmias by directly affecting multiple ion channels, which is a pathway distinct from heart ischemia and has received less concern in clinical treatment.

Objective: To evaluate the efficacy of some common clinical antiarrhythmic drugs for CO-induced arrhythmias, and to propose a potential pharmacotherapy for CO-induced arrhythmias through the virtual pathological cell and tissue models.

Methods: Two pathological models describing CO effects on healthy and failing hearts were constructed as control baseline models. After this, we first assessed the efficacy of some common antiarrhythmic drugs like ranolazine, amiodarone, nifedipine, etc., by incorporating their ion channel-level effects into the cell model. Cellular biomarkers like action potential duration and tissue-level biomarkers such as the QT interval from pseudo-ECGs were obtained to assess the drug efficacy. In addition, we also evaluated multiple specific IKr activators in a similar way to multi-channel blocking drugs, as the IKr activator showed great potency in dealing with CO-induced pathological changes.

Results: Simulation results showed that the tested seven antiarrhythmic drugs failed to rescue the heart from CO-induced arrhythmias in terms of the action potential and the ECG manifestation. Some of them even worsened the condition of arrhythmogenesis. In contrast, IKr activators like HW-0168 effectively alleviated the proarrhythmic effects of CO.

Conclusion: Current antiarrhythmic drugs including the ranolazine suggested in previous studies did not achieve therapeutic effects for the cardiotoxicity of CO, and we showed that the specific IKr activator is a promising pharmacotherapy for the treatment of CO-induced arrhythmias.
Regulation of T cell function by protein S-acylation
Authors: West Savannah J. , Boehning Darren , Akimzhanov Askar M.
Published: November 2022

S-acylation, the reversible lipidation of free cysteine residues with long-chain fatty acids, is a highly dynamic post-translational protein modification that has recently emerged as an important regulator of the T cell function. The reversible nature of S-acylation sets this modification apart from other forms of protein lipidation and allows it to play a unique role in intracellular signal transduction. In recent years, a significant number of T cell proteins, including receptors, enzymes, ion channels, and adaptor proteins, were identified as S-acylated. It has been shown that S-acylation critically contributes to their function by regulating protein localization, stability and protein-protein interactions. Furthermore, it has been demonstrated that zDHHC protein acyltransferases, the family of enzymes mediating this modification, also play a prominent role in T cell activation and differentiation. In this review, we aim to highlight the diversity of proteins undergoing S-acylation in T cells, elucidate the mechanisms by which reversible lipidation can impact protein function, and introduce protein acyltransferases as a novel class of regulatory T cell proteins.