bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of biallelic variations of CEP70 in patients with male infertility
Authors: Ruan Tiechao , Yang Yihong , Jiang Chuan , Shen Gan , Li Dingming , Shen Ying 
Published: March 2023

IntroductionMale infertility is a severe health issue caused by complex and multifactorial pathological conditions. Genetic factors are a major cause of male infertility. CEP70, a centrosomal protein, has been reported to play an important role in male reproduction in mice. However, the role of CEP70 in human male infertility is limited.MethodsWhole exome sequencing and Sanger sequencing were used to identify the genetic cause of the infertile patients. Papanicolaou staining, scanning electron microscopy and transmission electron microscopy were further conducted to explore morphological and ultrastructural defects in spermatozoa from the patient. Immunofluorescence staining was used to detect the pathogenicity of the identified variants and the particular expression of CEP70 in testis.ResultsIn this study, we identified biallelic mutations of CEP70 in two unrelated infertile male individuals with oligoasthenoteratozoospermia that followed a recessive inheritance pattern. Papanicolaou staining, scanning electron microscopy and transmission electron microscopy showed that morphological and ultrastructural defects in the acrosome and flagellum of sperm from the patient in a pattern strikingly similar to that in Cep70−/− male mice. The results of immunofluorescence staining suggested that CEP70 was normally expressed in the acrosome and flagellum of control sperm but was hardly detected in the sperm of patient carrying CEP70 variation. We also explored the particular expression pattern of CEP70 during spermatogenesis in humans and mice.ConclusionsBiallelic mutations of CEP70 might be a novel genetic cause of human male infertility, which could potentially serve as a basis for genetic counseling and diagnosis of male infertility.
Expanding the apelin receptor pharmacological toolbox using novel fluorescent ligands
Authors: Williams Thomas L. , Macrae Robyn G. C. , Kuc Rhoda E. , Brown Alastair J. H. , Maguire Janet J. , Davenport Anthony P. 
Published: March 2023

IntroductionThe apelin receptor binds two distinct endogenous peptides, apelin and ELA, which act in an autocrine/paracrine manner to regulate the human cardiovascular system. As a class A GPCR, targeting the apelin receptor is an attractive therapeutic strategy. With improvements in imaging techniques, and the stability and brightness of dyes, fluorescent ligands are becoming increasingly useful in studying protein targets. Here, we describe the design and validation of four novel fluorescent ligands; two based on [Pyr1]apelin-13 (apelin488 and apelin647), and two based on ELA-14 (ELA488 and ELA647).MethodsFluorescent ligands were pharmacologically assessed using radioligand and functional in vitro assays. Apelin647 was validated in high content imaging and internalisation studies, and in a clinically relevant human embryonic stem cell-derived cardiomyocyte model. Apelin488 and ELA488 were used to visualise apelin receptor binding in human renal tissue.ResultsAll four fluorescent ligands retained the ability to bind and activate the apelin receptor and, crucially, triggered receptor internalisation. In high content imaging studies, apelin647 bound specifically to CHO-K1 cells stably expressing apelin receptor, providing proof-of-principle for a platform that could screen novel hits targeting this GPCR. The ligand also bound specifically to endogenous apelin receptor in stem cell-derived cardiomyocytes. Apelin488 and ELA488 bound specifically to apelin receptor, localising to blood vessels and tubules of the renal cortex.DiscussionOur data indicate that the described novel fluorescent ligands expand the pharmacological toolbox for studying the apelin receptor across multiple platforms to facilitate drug discovery.
Shift of combined ecotoxicity index in petroleum polluted soils during a bacterial remediation
Authors: Chai Xiaoyun , Wang Mutian , Fu Xiaowen , Zhang Wen , Huang Yujie , Germaine Kieran J. , Wang Jianing 
Published: March 2023

Introduction: Bioremediation has been shown to be an effective strategy for removing toxic pollutants from the environment, particularly organic chemicals such as petroleum hydrocarbons. This paper investigates the changes in toxicity of petroleum-contaminated soil as a result of microbial remediation processes.Methods: Changes in the ecotoxicity of the contaminated soil were examined using a plant, earthworm, enzyme activity and luminescent bacteria toxicity tests.Results: The results showed that bioremediation could effectively degrade petroleum hydrocarbon (C10–C40) pollutants. After 42 days of remediation, the petroleum hydrocarbon (C10–C40) content of Group A (bioaugmented polluted wetland soil) decreased from 1.66 g/kg to 1.00 g/kg, and the degradation rate was 40.6%. The petroleum hydrocarbon (C10–C40) content of Group B (bioaugmented polluted farmland soil decreased from 4.00 g/kg to 1.94 g/kg, and the degradation rate was 51.6%. During the microbial remediation progress, the ecological toxicity of petroleum-contaminated soil first increased and then decreased. The photosynthetic pigment content index in the higher plant toxicity test, the earthworm survival index and the soil catalase activity all showed good agreement with the relative luminescence index of extracted DCM/DMSO in the luminescent bacterial toxicity test. The soil toxicity decreased significantly after remediation. Specifically, the photosynthetic pigment content of wheat were inhibited in the soil during the whole process (remediation for 42 days), and decreased to the minimum on remediation day 21. The 7-day and 14-day survival rate of earthworms in Group A and Group B gradually decreased in the soil remediation process, and then gradually increased, survival rate at the end of remediation was higher than at the beginning. Soil catalase activity was significantly negatively correlated with petroleum hydrocarbon (C10–C40) content (−0.988, −0.989). The ecological toxicity of contaminated soil reached to the maximum on the 21st day of remediation, relative luminosity of luminescent bacteria in dichloromethane/dimethyl sulfoxide extracts from Group A and Group B were 26.3% and 16.3%, respectively.Conclusion: Bioremediation could effectively degrade petroleum hydrocarbon (C10–C40) pollutants. Wheat photosynthetic pigment content, earthworm survival rate, soil catalase activity and relative luminescence of luminescent bacteria can better indicate the ecological toxicity of petroleum-contaminated soil in bioremediation process.
Impact of forest fire on radial growth of tree rings and their element concentrations of Pinus sylvestris and Larix gmelinii in northern China
Authors: Wei Mao , Guo Xinbin , Ma Yuanfan , Tigabu Mulualem , Zheng Wenxia , Liu Mengxia , Guo Futao 
Published: March 2023

AimsThrough analyzing the responses of the radial growth and element concentrations (B, Mg, Al, K, Ca, Mn, Fe, Zn, Na, P, Ni, and Cu) of tree rings of two dominant tree species to forest fires, we aimed to investigate the relationship between tree rings and the fires.MethodsWe sampled wood cores of Pinus sylvestris and Larix gmelinii in the northern forest region of China, where forest fires happened in 1990 and 2008. The ring-width growth of P. sylvestris and L. gmelinii from 1986 to 1995 and 2004 to 2013 in two sites of Tahe County were measured. Element concentrations in tree rings were determined using inductively coupled plasma mass spectrometry (ICP-MS).ResultsOur results showed that tree-ring radial growth was largely reduced after the fire, together with the increase in concentrations of B, Al, Mn, and Fe but the decrease in some samples in K. Strong correlations were observed between tree-ring growth and concentrations of Mg and Mn of P. sylvestris and Znof L. gmelinii.DiscussionThe results provide evidence that variations in tree-ring growth and element concentrations, particularly concentrations of B, Al, Mn, and Fe, are potentially useful to monitor forest fires, which add new insights into the study of forest fire history.
Overexpression of CHAF1A is associated with poor prognosis, tumor immunosuppressive microenvironment and treatment resistance
Authors: Sun Xia , Ma Qiushuang , Cheng Yahong , Huang Huangwei , Qin Jing , Zhang Mengchen , Qu Sifeng 
Published: March 2023

Background: As distinct marker of proliferating cells, chromatin assembly factor-1 (CAF-1) was critical in DNA replication. However, there is paucity information about the clinical significance, functions and co-expressed gene network of CHAF1A, the major subunit in CAF-1, in cancer.Methods: Bioinformatic analysis of CHAF1A and its co-expression gene network were performed using various public databases. Functional validation of CHAF1A was applied in breast cancer.Results: Overexpression of CHAF1A was found in 20 types of cancer tissues. Elevated expression of CHAF1A was positively correlated with breast cancer progression and poor patients’ outcome. The analysis of co-expression gene network demonstrated CHAF1A was associated with not only cell proliferation, DNA repair, apoptosis, but cancer metabolism, immune system, and drug resistance. More importantly, higher expression of CHAF1A was positively correlated with immunosuppressive microenvironment and resistance to endocrine therapy and chemotherapy. Elevated expression of CHAF1A was confirmed in breast cancer tissues. Silencing of CHAF1A can significantly inhibit cell proliferation in MDA-MB-231 cells.Conclusion: The current work suggested that overexpression of CHAF1A can be used as diagnostic and poor prognostic biomarker of breast cancer. Higher expression of CHAF1A induced fast resistance to endocrine therapy and chemotherapy, it may be a promising therapeutic target and a biomarker to predict the sensitivity of immunotherapy in breast cancer.
Machine learning used for simulation of MitraClip intervention: A proof-of-concept study
Authors: Dabiri Yaghoub , Mahadevan Vaikom S. , Guccione Julius M. , Kassab Ghassan S. 
Published: March 2023

Introduction: Severe mitral regurgitation (MR) is a mitral valve disease that can lead to lifethreatening complications. MitraClip (MC) therapy is a percutaneous solution for patients who cannot tolerate surgical solutions. In MC therapy, a clip is implanted in the heart to reduce MR. To achieve optimal MC therapy, the cardiologist needs to foresee the outcomes of different scenarios for MC implantation, including the location of the MC. Although finite element (FE) modeling can simulate the outcomes of different MC scenarios, it is not suitable for clinical usage because it requires several hours to complete.Methods: In this paper, we used machine learning (ML) to predict the outcomes of MC therapy in less than 1 s. Two ML algorithms were used: XGBoost, which is a decision tree model, and a feed-forward deep learning (DL) model. The MC location, the geometrical attributes of the models and baseline stress and MR were the features of the ML models, and the predictions were performed for MR and maximum von Mises stress in the leaflets. The parameters of the ML models were determined to achieve the minimum errors obtained by applying the ML models on the validation set.Results: The results for the test set (not used during training) showed relative agreement between ML predictions and ground truth FE predictions. The accuracy of the XGBoost models were better than DL models. Mean absolute percentage error (MAPE) for the XGBoost predictions were 0.115 and 0.231, and the MAPE for DL predictions were 0.154 and 0.310, for MR and stress, respectively.Discussion: The ML models reduced the FE runtime from 6 hours (on average) to less than 1 s. The accuracy of ML models can be increased by increasing the dataset size. The results of this study have important implications for improving the outcomes of MC therapy by providing information about the outcomes of MC implantation in real-time.
Meningoencephalitis associated with GAD65 autoimmunity
Authors: Kuang Zuying , Baizabal-Carvallo José Fidel , Mofatteh Mohammad , Xie Sifen , Pan Mengqiu , Ye Jinlong , Zhou Lihua , Yang Shuiquang , Wang Zhanhang , Chen Yimin , Li Yaqin 
Published: March 2023

BackgroundEncephalitis has been recognized in patients with autoimmunity related to the 65-kDa isoform of glutamic acid decarboxylase (GAD65) antibodies; however, patients with meningoencephalitis associated with those antibodies have been rarely identified in the medical literature. We aimed to define the frequency, clinical features, response to therapy, and functional outcomes of patients with meningoencephalitis associated with GAD antibodies.MethodsWe retrospectively studied consecutive patients attending a tertiary care center for evaluation of an autoimmune neurological disorder from January 2018 to June 2022. The modified Rankin Scale (mRS) was used to assess the functional outcome at the last follow-up.ResultsWe evaluated 482 patients with confirmed autoimmune encephalitis during the study period. Four among the 25 patients with encephalitis related to GAD65 antibodies were identified. One patient was excluded owing to the coexistence of NMDAR antibodies. Three male patients aged 36, 24, and 16 years had an acute (n = 1) or subacute (n = 2) onset of confusion, psychosis, cognitive symptoms, seizures, or tremor. No patient had fever or clinical signs of meningeal irritation. Mild pleocytosis (&lt;100 leukocytes/106) was identified in two patients, whereas one patient had normal CSF. Following immunotherapy with corticosteroids (n = 3) or intravenous immunoglobulin (n = 1), significant improvement was observed in all three cases, achieving a good outcome (mRS 1) in all cases.ConclusionMeningoencephalitis is an uncommon presentation of GAD65 autoimmunity. Patients present with signs of encephalitis but with meningeal enhancement and have good outcomes.
Lacticaseibacilli attenuated fecal dysbiosis and metabolome changes in Candida-administered bilateral nephrectomy mice
Authors: Chancharoenthana Wiwat , Kamolratanakul Supitcha , Visitchanakun Peerapat , Sontidejkul Supistha , Cheibchalard Thanya , Somboonna Naraporn , Settachaimongkon Sarn , Leelahavanichkul Asada 
Published: March 2023

The impacts of metabolomic changes (reduced short-chain-fatty acids; SCFAs) in uremic condition is not fully understood. Once dailyCandidagavage with or without probiotics (different times of administration) for 1 week prior to bilateral nephrectomy (Bil Nep) in 8-week-old C57BL6 mice as the possible models more resemble human conditions were performed.Candida-administered Bil Nep mice demonstrated more severe conditions than Bil Nep alone as indicated by mortality (n = 10/group) and other 48 h parameters (n = 6-8/group), including serum cytokines, leaky gut (FITC-dextran assay, endotoxemia, serum beta-glucan, and loss of Zona-occludens-1), and dysbiosis (increasedEnterobacteriaceaewith decreased diversity in microbiome analysis) (n = 3/group for fecal microbiome) without the difference in uremia (serum creatinine). With nuclear magnetic resonance metabolome analysis (n = 3-5/group), Bil Nep reduced fecal butyric (and propionic) acid and blood 3-hydroxy butyrate compared with sham andCandida-Bil Nep altered metabolomic patterns compared with Bil Nep alone. Then,Lacticaseibacillus rhamnosusdfa1 (SCFA-producingLacticaseibacilli) (n = 8/group) attenuated the model severity (mortality, leaky gut, serum cytokines, and increased fecal butyrate) of Bil Nep mice (n = 6/group) (regardless ofCandida). In enterocytes (Caco-2 cells), butyrate attenuated injury induced by indoxyl sulfate (a gut-derived uremic toxin) as indicated by transepithelial electrical resistance, supernatant IL-8,NFκBexpression, and cell energy status (mitochondria and glycolysis activities by extracellular flux analysis). In conclusion, the reduced butyrate by uremia was not enhanced byCandidaadministration; however, the presence ofCandidain the gut induced a leaky gut that was attenuated by SCFA-producing probiotics. Our data support the use of probiotics in uremia.
Model-interpreted outcomes of artificial neural networks classifying immune biomarkers associated with severe infections in ICU
Authors: Martinez Gustavo Sganzerla , Ostadgavahi Ali Toloue , Al-Rafat Abdullah Mahmud , Garduno Alexis , Cusack Rachael , Bermejo-Martin Jesus Francisco , Martin-Loeches Ignacio , Kelvin David 
Published: March 2023

IntroductionMillions of deaths worldwide are a result of sepsis (viral and bacterial) and septic shock syndromes which originate from microbial infections and cause a dysregulated host immune response. These diseases share both clinical and immunological patterns that involve a plethora of biomarkers that can be quantified and used to explain the severity level of the disease. Therefore, we hypothesize that the severity of sepsis and septic shock in patients is a function of the concentration of biomarkers of patients.MethodsIn our work, we quantified data from 30 biomarkers with direct immune function. We used distinct Feature Selection algorithms to isolate biomarkers to be fed into machine learning algorithms, whose mapping of the decision process would allow us to propose an early diagnostic tool.ResultsWe isolated two biomarkers, i.e., Programmed Death Ligand-1 and Myeloperoxidase, that were flagged by the interpretation of an Artificial Neural Network. The upregulation of both biomarkers was indicated as contributing to increase the severity level in sepsis (viral and bacterial induced) and septic shock patients.DiscussionIn conclusion, we built a function considering biomarker concentrations to explain severity among sepsis, sepsis COVID, and septic shock patients. The rules of this function include biomarkers with known medical, biological, and immunological activity, favoring the development of an early diagnosis system based in knowledge extracted from artificial intelligence.
Retinal vein changes after treatment with aflibercept and PRP in high-risk proliferative diabetic retinopathy
Authors: Zhao Hui , Wang Jundong , Li Shuting , Bao Ying , Zheng Xiaoxia , Tao Yuan , Wang Hong 
Published: March 2023

ObjectiveThe objective of the study was to investigate the effectiveness of aflibercept and panretinal photocoagulation (PRP) in the treatment of proliferative diabetic retinopathy (PDR).MethodsA retrospective analysis was performed on 59 patients (59 eyes) with high-risk PDR who were treated with aflibercept and PRP between January 2018 and December 2019. The best corrected visual acuity (BCVA), central foveal thickness (CFT), and retinal vein diameter post-treatment were compared to those before the treatment.ResultsThe best corrected visual acuity (BCVA) at 6 months (0.49 ± 0.14 logMAR), 12 months (0.54 ± 0.15 logMAR), 18 months (0.48 ± 0.15 logMAR), and 24 months (0.51 ± 0.15 logMAR) post-treatment were superior to the pre-treatment measurement (0.65 ± 0.18 logMAR). The central foveal thickness (CFT) at 6 months (310.67 ± 52.53 μm), 12 months (295.98 ± 45.65 μm), 18 months (282.56 ± 43.57 μm), and 24 months (281.53 ± 51.16 μm) post-treatment were lower than the pre-treatment measurement (456.53 ± 51.49 μm); the retinal vein diameter at 12 months (310.13 ± 24.60 μm), 18 months (309.50 ± 31.58 μm), and 24 months (317.00 ± 27.54 μm) post-treatment were lower than the pre-treatment measurement (361.81 ± 30.26 μm).ConclusionAflibercept intravitreal injection and panretinal photocoagulation may morphologically reverse retinal vein diameter and venous beading in high-risk proliferative diabetic retinopathy.
Chemokines in patients with Alzheimer's disease: A meta-analysis
Authors: Wang Hecheng , Zong Yu , Zhu Lei , Wang Weiyi , Han Yanshuo 
Published: March 2023

BackgroundAlzheimer's disease (AD) is the most common neurodegenerative disease in elderly people. Many researches have reported that neuroinflammation is related to AD. Chemokines are a class of small cytokines that play important roles in cell migration and cell communication, which involved in neuroinflammation. Up to now there is no meta-analysis to explore the difference of chemokines between AD patients and healthy elderly individuals.MethodWe searched PubMed, Web of science, Cochrane library, EMBASE and Scopus databases from inception to January 2022. Data were extracted by two independent reviewers, and the Review Manager 5.3 was used for the meta-analysis.ResultThirty-two articles were included and analyzed. The total number of participants in the included study was 3,331. We found that the levels of CCL5 (SMD = 2.56, 95% CI: 1.91–3.21), CCL15 (SMD = 3.30, 95% CI: 1.48–5.13) and IP-10 (SMD = 3.88, 95% CI: 1.84–5.91) in the plasma of AD patients were higher than healthy people. MCP-1 protein (SMD = 0.67, 95% CI: 0.29–1.05) in the AD patients' CSF was higher than healthy controls.ConclusionThese results suggested that chemokines may play an important role in AD. These findings could provide evidences for the diagnosis and treatment of AD.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021278736, identifier: CRD42021278736.
Hierarchical strategy for sEMG classification of the hand/wrist gestures and forces of transradial amputees
Authors: Leone Francesca , Mereu Federico , Gentile Cosimo , Cordella Francesca , Gruppioni Emanuele , Zollo Loredana 
Published: March 2023

IntroductionThe myoelectric control strategy, based on surface electromyographic signals, has long been used for controlling a prosthetic system with multiple degrees of freedom. Several methods classify gestures and force levels but the simultaneous real-time control of hand/wrist gestures and force levels did not yet reach a satisfactory level of effectiveness.MethodsIn this work, the hierarchical classification approach, already validated on 31 healthy subjects, was adapted for the real-time control of a multi-DoFs prosthetic system on 15 trans-radial amputees. The effectiveness of the hierarchical classification approach was assessed by evaluating both offline and real-time performance using three algorithms: Logistic Regression (LR), Non-linear Logistic Regression (NLR), and Linear Discriminant Analysis (LDA).ResultsThe results of this study showed the offline performance of amputees was promising and comparable to healthy subjects, with mean F1 scores of over 90% for the “Hand/wrist gestures classifier” and 95% for the force classifiers, implemented with the three algorithms with features extraction (FE). Another significant finding of this study was the feasibility of using the hierarchical classification strategy for real-time applications, due to its ability to provide a response time of 100 ms while maintaining an average online accuracy of above 90%.DiscussionA possible solution for real-time control of both hand/wrist gestures and force levels is the combined use of the LR algorithm with FE for the "Hand/wrist gestures classifier", and the NLR with FE for the Spherical and Tip force classifiers.