bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondria and cytochrome components released into the plasma of severe COVID-19 and ICU acute respiratory distress syndrome patients
Authors: Chen Zhuo Zhen , Johnson Lloyd , Trahtemberg Uriel , Baker Andrew , Huq Saaimatul , Dufresne Jaimie , Bowden Peter , Miao Ming , Ho Ja-An , Hsu Cheng-Chih , dos Santos Claudia C. , Marshall John G. 
Published: April 2023

Abstract
Introduction
Proteomic analysis of human plasma by LC–ESI–MS/MS has discovered a limited number of new cellular protein biomarkers that may be confirmed by independent biochemical methods. Analysis of COVID-19 plasma has indicated the re-purposing of known biomarkers that might be used as prognostic markers of COVID-19 infection. However, multiple molecular approaches have previously indicated that the SARS-COV2 infection cycle is linked to the biology of mitochondria and that the response to infections may involve the action of heme containing oxidative enzymes.

Methods
Human plasma from COVID-19 and ICU-ARDS was analyzed by classical analytical biochemistry techniques and classical frequency-based statistical approaches to look for prognostic markers of severe COVID-19 lung damage. Plasma proteins from COVID-19 and ICU-ARDS were identified and enumerated versus the controls of normal human plasma (NHP) by LC–ESI–MS/MS. The observation frequency of proteins detected in COVID-19 and ICU-ARDS patients were compared to normal human plasma, alongside random and noise MS/MS spectra controls, using the Chi Square (χ2) distribution.

Results
PCR showed the presence of MT-ND1 DNA in the plasma of COVID-19, ICU-ARDS, as well as normal human plasma. Mitochondrial proteins such as MRPL, L2HGDH, ATP, CYB, CYTB, CYP, NDUF and others, were increased in COVID-19 and ICU-ARDS plasma. The apparent activity of the cytochrome components were tested alongside NHP by dot blotting on PVDF against a purified cytochrome c standard preparation for H2O2 dependent reaction with luminol as measured by enhanced chemiluminescence (ECL) that showed increased activity in COVID-19 and ICU-ARDS patients.

Discussion
The results from PCR, LC–ESI–MS/MS of tryptic peptides, and cytochrome ECL assays confirmed that mitochondrial components were present in the plasma, in agreement with the established central role of the mitochondria in SARS-COV-2 biology. The cytochrome activity assay showed that there was the equivalent of at least nanogram amounts of cytochrome(s) in the plasma sample that should be clearly detectable by LC–ESI–MS/MS. The release of the luminol oxidase activity from cells into plasma forms the basis of a simple and rapid test for the severity of cell damage and lung injury in COVID-19 infection and ICU-ARDS.

Graphical Abstract
Modulating tumour metabolism enhances gold nanoparticle radiosensitisation in HPV-negative head and neck cancer
Authors: Feng Jie , Pathak Varun , Byrne Niall M. , Wang Tongchuan , Yin Cancan , Medina Reinhold J. , Coulter Jonathan A. 
Published: April 2023

AbstractBackgroundRadiotherapy is a major therapeutic modality for locally advanced head and neck cancer. However, the effectiveness of radiotherapy is hindered by resistance mechanisms, most notably hypoxia, leading to unfavourable treatment outcomes. In this study, we investigate the radiosensitising potential of AuNPs in combination with the complex III electron transport chain inhibitor, using models of head and neck cancer.ResultsAuNP intracellular accumulation occurred in a concentration-dependent manner and was not influenced by microenvironmental oxygen levels, with citrate capped 15 nm AuNPs readily internalised, accumulating primarily within the cytoplasmic compartment. Pre-treatment with atovaquone had a profound and rapid impact on oxygen consumption, promoting a glycolytic switch under both normoxic and hypoxic conditions, a finding underlined by the concurrent increase in extracellular acidification. AuNPs alone sensitised FaDu cells to radiation under atmospheric oxygen conditions, producing a sensitiser enhancement ratio (SER) of 1.37. In combination with atovaquone, maximum dose enhancements were achieved yielding a SER value of 1.43 and 2.1 under normoxic and hypoxic conditions, respectively. Studies to elucidate the underlying mechanism of radiosensitisation revealed S-phase accumulation and a significant increase in apoptosis. Additionally, combined treatment significantly increased yields of unrepaired DNA double strand breaks, indicating increased yields of DNA double strand break damage.ConclusionsTaken together, we believe this to be the first work providing evidence that AuNP radiosensitisation can be enhanced via metabolic modulation. This study reveals the dual action of both physical and biological pathways of AuNPs radiosensitisation, resulting in superior radiotherapeutic effects.
Genetic algorithm-based feature selection with manifold learning for cancer classification using microarray data
Authors: Wang Zixuan , Zhou Yi , Takagi Tatsuya , Song Jiangning , Tian Yu-Shi , Shibuya Tetsuo 
Published: April 2023

Abstract
Background
Microarray data have been widely utilized for cancer classification. The main characteristic of microarray data is “large p and small n” in that data contain a small number of subjects but a large number of genes. It may affect the validity of the classification. Thus, there is a pressing demand of techniques able to select genes relevant to cancer classification.

Results
This study proposed a novel feature (gene) selection method, Iso-GA, for cancer classification. Iso-GA hybrids the manifold learning algorithm, Isomap, in the genetic algorithm (GA) to account for the latent nonlinear structure of the gene expression in the microarray data. The Davies–Bouldin index is adopted to evaluate the candidate solutions in Isomap and to avoid the classifier dependency problem. Additionally, a probability-based framework is introduced to reduce the possibility of genes being randomly selected by GA. The performance of Iso-GA was evaluated on eight benchmark microarray datasets of cancers. Iso-GA outperformed other benchmarking gene selection methods, leading to good classification accuracy with fewer critical genes selected.

Conclusions
The proposed Iso-GA method can effectively select fewer but critical genes from microarray data to achieve competitive classification performance.
Deep learning-based prediction of osseointegration for dental implant using plain radiography
Authors: Oh Seok , Kim Young Jae , Kim Jeseong , Jung Joon Hyeok , Lim Hun Jun , Kim Bong Chul , Kim Kwang Gi 
Published: April 2023

Abstract
Background
In this study, we investigated whether deep learning-based prediction of osseointegration of dental implants using plain radiography is possible.

Methods
Panoramic and periapical radiographs of 580 patients (1,206 dental implants) were used to train and test a deep learning model. Group 1 (338 patients, 591 dental implants) included implants that were radiographed immediately after implant placement, that is, when osseointegration had not yet occurred. Group 2 (242 patients, 615 dental implants) included implants radiographed after confirming successful osseointegration. A dataset was extracted using random sampling and was composed of training, validation, and test sets. For osseointegration prediction, we employed seven different deep learning models. Each deep-learning model was built by performing the experiment 10 times. For each experiment, the dataset was randomly separated in a 60:20:20 ratio. For model evaluation, the specificity, sensitivity, accuracy, and AUROC (Area under the receiver operating characteristic curve) of the models was calculated.

Results
The mean specificity, sensitivity, and accuracy of the deep learning models were 0.780–0.857, 0.811–0.833, and 0.799–0.836, respectively. Furthermore, the mean AUROC values ranged from to 0.890–0.922. The best model yields an accuracy of 0.896, and the worst model yields an accuracy of 0.702.

Conclusion
This study found that osseointegration of dental implants can be predicted to some extent through deep learning using plain radiography. This is expected to complement the evaluation methods of dental implant osseointegration that are currently widely used.
Effects of tissue degradation by collagenase and elastase on the biaxial mechanics of porcine airways
Authors: Mariano Crystal A. , Sattari Samaneh , Ramirez Gustavo O. , Eskandari Mona 
Published: April 2023

Abstract
Background
Common respiratory illnesses, such as emphysema and chronic obstructive pulmonary disease, are characterized by connective tissue damage and remodeling. Two major fibers govern the mechanics of airway tissue: elastin enables stretch and permits airway recoil, while collagen prevents overextension with stiffer properties. Collagenase and elastase degradation treatments are common avenues for contrasting the role of collagen and elastin in healthy and diseased states; while previous lung studies of collagen and elastin have analyzed parenchymal strips in animal and human specimens, none have focused on the airways to date.

Methods
Specimens were extracted from the proximal and distal airways, namely the trachea, large bronchi, and small bronchi to facilitate evaluations of material heterogeneity, and subjected to biaxial planar loading in the circumferential and axial directions to assess airway anisotropy. Next, samples were subjected to collagenase and elastase enzymatic treatment and tensile tests were repeated. Airway tissue mechanical properties pre- and post-treatment were comprehensively characterized via measures of initial and ultimate moduli, strain transitions, maximum stress, hysteresis, energy loss, and viscoelasticity to gain insights regarding the specialized role of individual connective tissue fibers and network interactions.

Results
Enzymatic treatment demonstrated an increase in airway tissue compliance throughout loading and resulted in at least a 50% decrease in maximum stress overall. Strain transition values led to significant anisotropic manifestation post-treatment, where circumferential tissues transitioned at higher strains compared to axial counterparts. Hysteresis values and energy loss decreased after enzymatic treatment, where hysteresis reduced by almost half of the untreated value. Anisotropic ratios exhibited axially led stiffness at low strains which transitioned to circumferentially led stiffness when subjected to higher strains. Viscoelastic stress relaxation was found to be greater in the circumferential direction for bronchial airway regions compared to axial counterparts.

Conclusion
Targeted fiber treatment resulted in mechanical alterations across the loading range and interactions between elastin and collagen connective tissue networks was observed. Providing novel mechanical characterization of elastase and collagenase treated airways aids our understanding of individual and interconnected fiber roles, ultimately helping to establish a foundation for constructing constitutive models to represent various states and progressions of pulmonary disease.
Co-profiling reveals distinct patterns of genomic chromatin accessibility and gene expression in pulmonary hypertension caused by chronic hypoxia
Authors: Yu Dongdong , Zhang Ting , Zhou Guangyuan , Wu Zeang , Xiao Rui , Zhang Han , Liu Bingxun , Li Xiangpan , Ruiz Matthieu , Dupuis Jocelyn , Zhu Liping , Hu Qinghua 
Published: April 2023

AbstractIntroductionAberrant gene expression is a key mechanism underlying pulmonary hypertension (PH) development. The alterations of genomic chromatin accessibility and their relationship with the aberrant gene expressions in PH are poorly understood. We used bulk Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) and RNA sequencing (RNA-seq) in pulmonary artery smooth muscle cells (PASMCs) of chronic hypoxia-exposed rats mimicking group 3 human PH.MethodsAdult Sprague Dawley rats were commercially obtained from Hunan SJA (Hunan SJA Laboratory Animal Co., Changsha, China) and randomizedly allocated into four groups exposing to nomobaric hypoxia or normoxia for 1 or 28 days respectively. After the assessment of pulmonary hemodynamics, smooth muscle cells were isolated from intralobular arteries and simultaneously subjected to bulk Assay of ATAC-seq and RNA-seq.ResultsHypoxic exposure for continuous 28-days, but not for 1-day, induced established PH phenotypes in rats. ATAC-seq revealed a major distribution of differential accessibility regions (DARs) annotated to the genome in out-of-promoter regions, following 1-day or 28-days hypoxia. 1188 DAR-associated genes and 378 differentially expressed genes (DEGs) were identified in rats after exposure to 1-day hypoxia, while 238 DAR-associated genes and 452 DEGs for 28-days hypoxia. Most of the DAR-associated genes or DEGs in 1-day did not overlap with that of 28-days hypoxia. A Pearson correlation analysis indicated no significant correlation between ATAC-seq and RNA-seq.ConclusionsThe alterations in genomic chromatin accessibility and genes expression of PASMCs in the initial stage of hypoxia are distinct from the established stage of hypoxia-induced PH. The genomic differential accessibility regions may not be the main mechanisms directly underlying the differentially expressed genes observed either in the initial or established stages of PH. Thus the time-course alterations of gene expression and their possible indirect link with genomic chromatin accessibility warrant more attention in mechanistic study of pulmonary hypertension.
Target response controlled enzyme activity switch for multimodal biosensing detection
Authors: Zhang Lu , Wu Haiping , Chen Yirong , Zhang Songzhi , Song Mingxuan , Liu Changjin , Li Jia , Cheng Wei , Ding Shijia 
Published: April 2023

AbstractHow to achieve delicate regulation of enzyme activity and empower it with more roles is the peak in the field of enzyme catalysis research. Traditional proteases or novel nano-enzymes are unable to achieve stimulus-responsive activity modulation due to their own structural limitations. Here, we propose a novel Controllable Enzyme Activity Switch, CEAS, based on hemin aggregation regulation, to deeply explore its regulatory mechanism and develop multimodal biosensing applications. The core of CEAS relies on the dimerizable inactivation of catalytically active center hemin and utilizes a DNA template to orderly guide the G4-Hemin DNAzyme to tightly bind to DNA-Hemin, thereby shutting down the catalytic ability. By customizing the design of the guide template, different target stimulus responses lead to hemin dimerization dissociation and restore the synergistic catalysis of G4-Hemin and DNA-Hemin, thus achieving a target-regulated enzymatic activity switch. Moreover, the programmability of CEAS allowed it easy to couple with a variety of DNA recognition and amplification techniques, thus developing a series of visual protein detection systems and highly sensitive fluorescent detection systems with excellent bioanalytical performance. Therefore, the construction of CEAS is expected to break the limitation of conventional enzymes that cannot be targetable regulated, thus enabling customizable enzymatic reaction systems and providing a new paradigm for controllable enzyme activities.
Graphical Abstract
Impact of leptin or melatonin on Sema4D overexpression-related bone metabolism
Authors: Lin Zhenen , Xiong Shengren , Lin Yu , Li Zhaohui , Xie Dan , Lin Xuchao , Chen Xuesheng , Lin Xueyi 
Published: April 2023

Abstract
Purpose
The current study aims to investigate the regulatory impact of leptin or melatonin on bone metabolism as well as the underlying mechanism in conjunction with Sema4D (monoclonal antibody to semaphorin 4D).

Methods
Rats were used to create the osteoporosis model utilizing the OVX (OVariectomize) technique. Rat tibial specimens from each side were collected for three-dimensional reconstruction and Micro-CT scanning examination. The Hematoxylin-osinstaining (HE) staining technique was used to determine the pathological condition of bone tissues. The ELISA (Enzyme-Linked Immunosorbent Assay) assay was used to measure the amount of estradiol present in the serum. In the current study, there were six groups: control, OVX, OVX + NL (no load group), OVX + Sema4D, OVX + Sema4D + leptin, and OVX + Sema4D + MT (melatonin). Rats were given injections of the Sema4D or leptin overexpressing vectors via the tail vein in accordance with the aforementioned classification. By using a high-resolution micro-CT technology, 3D bone structure was discovered. The activity of tartrate-resistant acid phosphatase-5b (TRAP-5b) and bone-derived alkaline phosphatase (BALP) in serum was assessed using an ELISA. The number of osteoclasts in the metaphysis of the upper tibia was determined using TRAP (tartrate-resistant acid phosphatase) staining. Immunohistochemistry was used to find leptin and bone morphogenetic protein-2 (BMP-2) expressions in bone tissue.

Results
The BV/TV (Bone volume/Tissue volume), Tb.N (Trabecular number), BMD (Bone Mineral Density), and BMC (Bone Mineral Content) levels were significantly higher in the OVX + Sema4D + leptin and OVX + Sema4D + MT groups compared to OVX + NL, while Tb.Sp (Trabecular separation) levels were significantly lower. In contrast to the OVX group, the bone trabeculae in the OVX + Sema4D + leptin and OVX + Sema4D + MT groups had a relatively complete structure and tended to be organized closely. The amount of bone trabeculae grew drastically, whereas the proportion of TRAP-positive osteoclasts declined dramatically. BMP-2 and leptin were also elevated, while BALP and TRAP-5b activity was reduced.

Conclusion
Leptin or melatonin improved Sema4d's role in trabecular bone microstructure, bone production, and repairment of trabecular bone loss in osteoporosis rats.
Equivalent values between anterior vertebral height, wedge ratio, and wedge angle for evaluating vertebral mobility and deformity in osteoporotic vertebral fractures: a conventional observational study
Authors: Sato Kozo , Kogawa Masakazu , Yamada Yuichiro , Yamashiro Masahiro , Kasama Fumio , Matsuda Michimasa 
Published: April 2023

Abstract
Background
Vertebral mobility (V-mobility) has been used to diagnose fresh osteoporotic vertebral fractures (OVFs) and determine bone union by setting cutoff values for these purposes. V-mobility is the difference in vertebral height on dynamic radiographs taken in the sitting and lateral decubitus or supine positions. The dimensions for V-mobility were presented as anterior vertebral height (Ha; mm), wedge ratio (WR; %), and wedge angle (WA; °) in previous reports. This study was performed to obtain WR and WA values equivalent to V-mobility of 1.0 mm in Ha.

Methods
Lateral radiographs of 284 OVFs (grade 1–3 deformed vertebrae) from T11 to L2 were obtained from 77 patients with OVF. V-mobility presented as Ha, posterior vertebral height, and WA was obtained by the difference in these dimensions on dynamic radiographs. The WR and WA values equivalent to 1.0 mm in Ha were obtained by dividing the V-mobility values for WR and WA by that for Ha.

Results
The mean WR values corresponding to 1.0 mm in Ha for grade 1, 2, and 3 vertebrae were 3.2% ± 1.4%, 3.2% ± 0.9%, and 3.4% ± 1.0%, respectively, and the corresponding value for grade 1–3 vertebrae was 3.3% ± 1.0%. The mean WA values corresponding to 1.0 mm in Ha for grade 1, 2, and 3 vertebrae were 1.5° ± 0.8°, 1.5° ± 0.6°, and 1.5° ± 0.8°, respectively, and the corresponding value for grade 1–3 vertebrae was 1.5° ± 0.7°.

Conclusions
The WR and WA values equivalent to V-mobility of 1.0 mm in Ha were 3.3% and 1.5°, respectively, in grade 1–3 vertebrae. These findings may be useful to secure a reliable value of V-mobility of OVFs using simultaneous measurements in three dimensions (Ha, WR, and WA) in clinical practice and to establish cutoff values for V-mobility to determine bone union.
Multiple local recurrences of primary sternal chondrosarcoma: tumor manipulation or self-seeding
Authors: Jalil Riad Abdel , Abdallah Farah A. 
Published: April 2023

Abstract
Background
Primary sternal chondrosarcoma, although rare, is the most common malignant tumor of the sternum. The gold standard treatment is complete surgical excision, which frequently causes the instability of the thorax necessitating future reconstruction. Local recurrence is common increasing the risk of distant metastasis.

Case presentation
A 60-year-old male patient was diagnosed with primary sternum chondrosarcoma and underwent surgical excision with negative resection margins. Later, he was found to have two local recurrences at 11 months and 37 months post initial excision. The two recurrences were surgically removed followed by local adjuvant radiation.

Conclusion
The seeding theories have been reported more frequently with relation to diagnostic biopsy procedures, tumor manipulation and self-seeding tumors. The patient developed two local recurrences despite total resection with negative margins, without concerns regarding seeding in distant metastasis.
Risk factors for postoperative acute kidney injury in overweight patients with acute type A aortic dissection
Authors: Xu Yu , Dai Shang-Tai , Liu Lin-Zhuo , Kong De-Mei , Guo Shi-Kui , Gong Kun-Mei 
Published: April 2023

Abstract
Objective
To analyze the clinical characteristics of patients with overweight acute type A aortic dissection, and to explore the risk factors of acute kidney injury in patients with overweight acute type A aortic dissection.

Methods
From March 2019 to February 2022, the clinical data of 71 patients with acute type a aortic dissection diagnosed by CTA and undergoing surgical treatment with BMI > 24 in the First People's Hospital of Yunnan Province were retrospectively analyzed, and analyzed by univariate and logistic multivariate analysis methods.

Results
The mean BMI of all included patients was 27.23, The mean surface area of all included human populations was 1.833. The mean age of all patients was (52.06 ± 10.71) years old, and 35 patients developed acute kidney injury after surgery. Multi-factor Logistics regression analysis confirmed the risk factors for postoperative acute kidney injury in overweight patients with acute type A aortic dissection, including gender, CPB transit time and intraoperative infusion of suspended red blood cells. Seven patients in the AKI group died in hospital after surgery and two patients died in the non-AKI group.

Conclusions
Among patients with overweight acute Type A aortic dissection, the incidence of AKI is 49.30%. According to multi-factor Logistics regression analysis, gender, CPB transit time and intraoperative suspended red blood cell volume are independent risk factors for postoperative acute kidney injury in patients with overweight acute Type A aortic dissection.
The functional and clinical roles of liquid biopsy in patient-derived models
Authors: Zhu Ziqing , Hu Erya , Shen Hong , Tan Jun , Zeng Shan 
Published: April 2023

AbstractThe liquid biopsy includes the detection of circulating tumor cells (CTCs) and CTC clusters in blood, as well as the detection of, cell-free DNA (cfDNA)/circulating tumor DNA (ctDNA) and extracellular vesicles (EVs) in the patient's body fluid. Liquid biopsy has important roles in translational research. But its clinical utility is still under investigation. Newly emerged patient-derived xenograft (PDX) and CTC-derived xenograft (CDX) faithfully recapitulate the genetic and morphological features of the donor patients’ tumor and patient-derived organoid (PDO) can mostly mimic tumor growth, tumor microenvironment and its response to drugs. In this review, we describe how the development of these patient-derived models has assisted the studies of CTCs and CTC clusters in terms of tumor biological behavior exploration, genomic analysis, and drug testing, with the help of the latest technology. We then summarize the studies of EVs and cfDNA/ctDNA in PDX and PDO models in early cancer diagnosis, tumor burden monitoring, drug test and response monitoring, and molecular profiling. The challenges faced and future perspectives of research related to liquid biopsy using patient-derived models are also discussed.