bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of ACKR4 as an immune checkpoint in pulmonary arterial hypertension
Authors: Jiang Chen-Yu , Wu Li-Wei , Liu Yi-Wei , Feng Bei , Ye Lin-Cai , Huang Xu , He Yang-Yang , Shen Yi , Zhu Yi-Fan , Zhou Xing-Liang , Jiang Dai-Ji , Qi Hai-Kun , Zhang Hao , Yan Yi 
Published: June 2023

ObjectiveInflammation is recognized as a contributor in the development of pulmonary arterial hypertension (PAH), and the recruitment and functional capacity of immune cells are well-orchestrated by chemokines and their receptors. This study is aimed at identification of critical chemokines in the progression of PAH via transcriptomic analysis.MethodsDifferentially expressed genes (DEGs) from lungs of PAH patients were achieved compared to controls based on Gene Expression Omnibus (GEO) database. Gene set enrichment analysis (GSEA) was applied for functional annotation and pathway enrichement. The abundance of immune cells was estimated by the xCell algorithm. Weighted correlation network analysis (WGCNA) was used to construct a gene expression network, based on which a diagnostic model was generated to determine its accuracy to distinguish PAH from control subjects. Target genes were then validated in lung of hypoxia-induce pulmonary hypertension (PH) mouse model.ResultsACKR4 (atypical chemokine receptor 4) was downregulated in PAH lung tissues in multiple datasets. PAH relevant biological functions and pathways were enriched in patients with low-ACKR4 level according to GSEA enrichment analysis. Immuno-infiltration analysis revealed a negative correlation of activated dendritic cells, Th1 and macrophage infiltration with ACKR4 expression. Three gene modules were associated with PAH via WGCNA analysis, and a model for PAH diagnosis was generated using CXCL12, COL18A1 and TSHZ2, all of which correlated with ACKR4. The ACKR4 expression was also downregulated in lung tissues of our experimental PH mice compared to that of controls.ConclusionsThe reduction of ACKR4 in lung tissues of human PAH based on transcriptomic data is consistent with the alteration observed in our rodent PH. The correlation with immune cell infiltration and functional annotation indicated that ACKR4 might serve as a protective immune checkpoint for PAH.
A residual network with geographical and meteorological attention for multi-year ENSO forecasts
Authors: Song Dan , Ling Yuting , Hao Tong , Li Wenhui , Liu Wen , Ren Tongwei , Wei Zhiqiang , Liu An-an 
Published: June 2023

IntroductionAs global temperatures continue to rise, extreme weather phenomena such as El Niño and the Southern Oscillation (ENSO) near the equatorial Pacific Ocean are occurring more frequently and leading to tropical cyclones, droughts, and a series of extreme weather disasters. Accurately predicting ENSO in advance can greatly reduce the serious damage to human society, economy, and ecological environment. However, existing methods often neglect the data relation between geographical regions and meteorological factors, hindering the accuracy of ENSO prediction.MethodsTo overcome this problem, we propose a residual network with geographical and meteorological attention to capture important geographical information and explore the spatio-temporal correlation of different meteorological factors. Specifically, we propose two main attention modules: (1) the Geographical Semantic Information Enhancement Module (GSIEM), which selectively attends to important geographical regions and filters out irrelevant noise through a spatial-axis attention map, and (2) the Meteorological Factors Discriminating Enhancement Module (MFDEM), which aims to learn the spatio-temporal dependency of different meteorological factors using a learnable channel-axis weight map. We then integrate our proposed two attention modules into the backbone using residual connection, enhancing the model's prediction ability.ResultsWe conducted extensive experimental comparisons and ablation studies to evaluate the performance of our proposed method. The results show that our method outperforms existing state-of-the-art methods in ENSO prediction, with a significant improvement in prediction accuracy.DiscussionOur proposed method effectively captures geographical and meteorological information, facilitating accurate ENSO prediction. The attention modules we proposed can effectively filter out irrelevant noise and learn the spatio-temporal dependency of different meteorological factors, contributing to the superior performance of our model. Overall, our study provides a novel approach for ENSO prediction and has great potential for practical applications.
A deep learning model for prediction of post hepatectomy liver failure after hemihepatectomy using preoperative contrast-enhanced computed tomography: a retrospective study
Authors: Xu Xiaoqing , Xing Zijian , Xu Zhiyao , Tong Yifan , Wang Shuxin , Liu Xiaoqing , Ren Yiyue , Liang Xiao , Yu Yizhou , Ying Hanning 
Published: June 2023

ObjectivePost-hepatectomy liver failure (PHLF) remains clinical challenges after major hepatectomy. The aim of this study was to establish and validate a deep learning model to predict PHLF after hemihepatectomy using preoperative contrast-enhancedcomputed tomography with three phases (Non-contrast, arterial phase and venous phase).Methods265 patients undergoing hemihepatectomy in Sir Run Run Shaw Hospital were enrolled in this study. The primary endpoint was PHLF, according to the International Study Group of Liver Surgery’s definition. In this study, to evaluate the proposed method, 5-fold cross-validation technique was used. The dataset was split into 5 folds of equal size, and each fold was used as a test set once, while the other folds were temporarily combined to form a training set. Performance metrics on the test set were then calculated and stored. At the end of the 5-fold cross-validation run, the accuracy, precision, sensitivity and specificity for predicting PHLF with the deep learning model and the area under receiver operating characteristic curve (AUC) were calculated.ResultsOf the 265 patients, 170 patients with left liver resection and 95 patients with right liver resection. The diagnosis had 6 types: hepatocellular carcinoma, intrahepatic cholangiocarcinoma, liver metastases, benign tumor, hepatolithiasis, and other liver diseases. Laparoscopic liver resection was performed in 187 patients. The accuracy of prediction was 84.15%. The AUC was 0.7927. In 170 left hemihepatectomy cases, the accuracy was 89.41% (152/170), and the AUC was 82.72%. The accuracy was 77.47% (141/182) with liver mass, 78.33% (47/60) with liver cirrhosis and 80.46% (70/87) with viral hepatitis.ConclusionThe deep learning model showed excellent performance in prediction of PHLF and could be useful for identifying high-risk patients to modify the treatment planning.
Non-invasive estimation of split renal function from routine 68Ga-SSR-PET/CT scans
Authors: Weissinger Matthias , Seyfried Kyra Celine , Ursprung Stephan , Castaneda-Vega Salvador , Seith Ferdinand , von Beschwitz Sebastian , Vogel Jonas , Ghibes Patrick , Nikolaou Konstantin , la Fougère Christian , Dittmann Helmut 
Published: June 2023

ObjectivePatients with impaired kidney function are at elevated risk for nephrotoxicity and hematotoxicity from peptide receptor radionuclide therapy (PPRT) for advanced neuroendocrine tumors. Somatostatin receptor (SSR)-PET/CT imaging is the method of choice to identify sufficient SSR expression as a prerequisite for PRRT. Therefore, our study aimed to explore whether split renal function could be evaluated using imaging data from routine SSR-PET/CT prior to PRRT.MethodsIn total, 25 consecutive patients who underwent SSR-PET/CT (Siemens Biograph mCT®) before PRRT between June 2019 and December 2020 were enrolled in this retrospective study. PET acquisition in the caudocranial direction started at 20 ± 0.5 min after an i.v. injection of 173 ± 20 MBq [68Ga]Ga-ha DOTATATE, and the kidneys were scanned at 32 ± 0.5 min p.i. The renal parenchyma was segmented semi-automatically using an SUV-based isocontour (SUV between 5 and 15). Multiple parameters including SUVmean of renal parenchyma and blood pool, as well as parenchyma volume, were extracted, and accumulation index (ACI: renal parenchyma volume/SUVmean) and total kidney accumulation (TKA: SUVmean x renal parenchyma volume) were calculated. All data were correlated with the reference standard tubular extraction rate (TER-MAG) from [99mTc]Tc-MAG3 scintigraphy and glomerular filtration rate (GFRCDK − EPI).ResultsSUVmean of the parenchymal tracer retention showed a negative correlation with TERMAG (r: −0.519, p &lt; 0.001) and GFRCDK − EPI (r: −0.555, p &lt; 0.001) at 32 min p.i. The herein-introduced ACI revealed a significant correlation (p &lt; 0.05) with the total tubular function (r: 0.482), glomerular renal function (r: 0.461), split renal function (r: 0.916), and absolute single-sided renal function (r: 0.549). The mean difference between the split renal function determined by renal scintigraphy and ACI was 1.8 ± 4.2 % points.ConclusionThis pilot study indicates that static [68Ga]Ga-ha DOTATATE PET-scans at 32 min p.i. may be used to estimate both split renal function and absolute renal function using the herein proposed “Accumulation Index” (ACI).
Abatacept to induce remission of peanut allergy during oral immunotherapy (ATARI): protocol for a phase 2a randomized controlled trial
Authors: Braun Camille , Azzano Pauline , Gingras-Lessard Florence , Roy Émilie , Samaan Kathryn , Graham François , Paradis Louis , Des Roches Anne , Bégin Philippe 
Published: June 2023

ContextWhile oral immunotherapy (OIT) has been shown to promote the remission of mild peanut allergy in young children, there is still an unmet need for a disease-modifying intervention for older patients and those with severe diseases. In mice models, abatacept, a cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) immunoglobulin fusion protein, has been shown to promote immune tolerance to food when used as an adjuvant to allergen immunotherapy. The goal of this study is to explore the potential efficacy of abatacept in promoting immune tolerance to food allergens during OIT in humans.MethodsIn this phase 2a proof-of-concept study (NCT04872218), 14 peanut-allergic participants aged from 14 to 55 years will be randomized at a 1:1 ratio to abatacept vs. placebo for the first 24 weeks of a peanut OIT treatment (target maintenance dose of 300 mg peanut protein). The primary outcome will be the suppression of the OIT-induced surge in peanut-specific IgE/total IgE at 24 weeks, relative to the baseline. Sustained unresponsiveness will be assessed as a secondary outcome starting at 36 weeks by observing incremental periods of peanut avoidance followed by oral food challenges.DiscussionThis is the first study assessing the use of abatacept as an adjuvant to allergen immunotherapy in humans. As observed in preclinical studies, the ability of abatacept to modulate the peanut-specific immune response during OIT will serve as a proxy outcome for the development of clinical tolerance, given the small sample size. The study will also test a new patient-oriented approach to sustained tolerance testing in randomized controlled trials.
Perceptions of medical students toward teledermatology as an educational tool: a cross-sectional study
Authors: Ureña-Paniego Clara , Soto-Moreno Alberto , Montero-Vílchez Trinidad , Martínez-López Antonio , Buendía-Eisman Agustín , Arias-Santiago Salvador 
Published: June 2023

IntroductionTeledermatology consultations have recently been on the rise, especially due to the SARS-CoV-2 pandemic. The role of teledermatology has been extensively discussed as a mean for the education of dermatology residents. Nevertheless, little has been explored on its use as a pedagogical tool for medical students. The objectives of this study were to assess the level of satisfaction of medical students with teledermatology and to evaluate their opinion about its use as an educational tool.MethodsA cross-sectional study was carried out at the Dermatology Department, Hospital Universitario Virgen de las Nieves, Granada (Spain). Participants were fourth-year medical students. Every student would spend half of their internship in face-to-face consultations and the other half in teledermatology consultations. Data was collected via self-administered questionnaires.ResultsEighty one students were finally surveyed, being 66.67% (73/81) female. A majority of students considered a mixed clinical internship model (face-to-face consultations combined with teledermatology) more suitable for obtaining higher marks in the subject of dermatology and in the Medical Intern Resident exam (p = 0.04). Nevertheless, face-to-face practice was considered more useful for their training as general practitioners (p = 0.04).ConclusionDespite the fact that students highly value doctor-patient relationship, teledermatology is considered a powerful educational tool.
The host transcriptome change involved in the inhibitory effect of exogenous interferon-γ on Getah virus replication
Authors: Li Jialei , Gao Xintao , Liu Xingjian , Wu Tong , Song Haozhi , Gao Weisong , Jia Hong , Li Yinü , Zhang Zhifang 
Published: June 2023

IntroductionGetah virus (GETV) has become a growing potential threat to the global livestock industry and public health. However, little is known about the viral pathogenesis and immune escape mechanisms, leading to ineffective control measures.MethodsIn this study, the antiviral activity of exogenous interferons (IFNs) was assessed by using western blotting (WB), real-time quantitative PCR (RT-qPCR) and indirect immunofluorescence assay (IFA). The comparative transcriptomics among mock- and GETV-infected (MOI = 0.1) ST cells with or without IFN-γ was performed by RNA-seq, and then the transcriptome profiling of GETV-infected ST cells and key pathways and putative factors involved in inhibitory effect of IFN-γ on GETV replication were analyzed by bioinformatics methods and RT-qPCR.ResultsThe results showed that treatment with IFN-γ could suppress GETV replication, and the inhibitory effect lasted for at least 48 h, while the exogenous IFN-α/ω and IFN-λ3 treatments failed to inhibit the viral infection and early replication in vitro. Furthermore, the blueprint of virus-host interaction was plotted by RNA-seq and RT-qPCR, showing systemic activation of inflammatory, apoptotic, and antiviral pathways in response to GETV infection, indicating viral hijacking and inhibition of innate host immunity such as IFN-I/III responses. Last and most importantly, activation of the JAK-STAT signaling pathway and complement and coagulation cascades may be a primary driver for IFN-γ-mediated inhibition of GETV replication.DiscussionThese findings revealed that GETV possessed the capability of viral immune escape and indicated that IFN-γ aided in the prevention and control of GETV, implying the potential molecular mechanism of suppression of GETV by IFN-γ, all of which warrant emphasis or further clarification.
Intraocular complement activation is related to retinal vascular and neuronal degeneration in myopic retinopathy
Authors: Zeng Ling , Li Xiaoning , Pan Wei , Tang Yao , Lin Ding , Wang Min , Cai Wang , Zhu Ruiling , Wan Jianbo , Huang Linghua , Xu Heping , Yang Zhikuan 
Published: June 2023

PurposeTo investigate the relationship between the intraocular levels of complement proteins and myopia-related retinal neuronal and vascular degeneration.MethodsAqueous humour from 147 myopic patients, including 60 low-myopia and 87 high-myopia were collected during Implantable Collamer Lens implantation surgery. All participants received comprehensive ophthalmic examinations, including logMAR best corrected visual acuity, axial length measurement, fundus photography and ocular B-scan ultrasonography. The myopic eyes were further classified into simple myopia (SM, n = 78), myopic posterior staphyloma (PS, n = 39) and PS with myopic chorioretinal atrophy (PS + CA, n = 30). Retinal thickness and vascular density in the macula (6 mm × 6 mm) and optic nerve head (4.5 mm × 4.5 mm) were measured using Optical Coherence Tomography (OCT) and OCT angiography (OCTA). The levels of complement proteins including C1q, C3, C3b/iC3b, C4, CFB, CFH, C2, C4b, C5, C5a, CFD, MBL and CFI in the aqueous humour were measured using the Luminex Multiplexing system. The real-time RT-PCR was conducted to examine the expression of complement genes (C1q, C2, C3, C4, CFI and CFD) in the guinea pig model of long-term form deprivation-induced myopic retinal degeneration.ResultsOCTA showed that retinal neuronal thickness and vascular density in superficial and deep layers of the macular zone as well as vascular density in the optic nerve head were progressively decreased from SM to PS and PS + CA (p &lt; 0.05). The aqueous humour levels of C1q, C3, C3b/iC3b, C4, CFB, CFH, C2, C4b, C5 and CFI were significantly higher in high-myopic eyes compared to those in low-myopic eyes. Further subgroup analysis revealed the highest levels of complement components/fragments in the PS + CA group. The intraocular levels of complement factors particularly C3b/iC3b and C4 were negatively correlated with macular zone deep layer retinal thickness and vascular density and optic nerve head vascular density. The expression of C2, C3 and C4 genes was significantly higher in guinea pig eyes with myopic retinal degeneration compared to control eyes.ConclusionsThe intraocular classical pathway and alternative pathway of the complement system are partially activated in pathological myopia. Their activation is related to the degeneration of retinal neurons and the vasculature in the macula and the vasculature in the optic nerve head.
Cochlear implantation impairs intracochlear microcirculation and counteracts iNOS induction in guinea pigs
Authors: Ernst Benjamin Philipp , Heinrich Ulf-Rüdiger , Fries Mathias , Meuser Regina , Rader Tobias , Eckrich Jonas , Stauber Roland H. , Strieth Sebastian 
Published: June 2023

IntroductionPreservation of residual hearing remains a great challenge during cochlear implantation. Cochlear implant (CI) electrode array insertion induces changes in the microvasculature as well as nitric oxide (NO)-dependent vessel dysfunction which have been identified as possible mediators of residual hearing loss after cochlear implantation.MethodsA total of 24 guinea pigs were randomized to receive either a CI (n = 12) or a sham procedure (sham) by performing a cochleostomy without electrode array insertion (n = 12). The hearing threshold was determined using frequency-specific compound action potentials. To gain visual access to the stria vascularis, a microscopic window was created in the osseous cochlear lateral wall. Cochlear blood flow (CBF) and cochlear microvascular permeability (CMP) were evaluated immediately after treatment, as well as after 1 and 2 h, respectively. Finally, cochleae were resected for subsequent immunohistochemical analysis of the iNOS expression.ResultsThe sham control group showed no change in mean CBF after 1 h (104.2 ± 0.7%) and 2 h (100.8 ± 3.6%) compared to baseline. In contrast, cochlear implantation resulted in a significant continuous decrease in CBF after 1 h (78.8 ± 8.1%, p &lt; 0.001) and 2 h (60.6 ± 11.3%, p &lt; 0.001). Additionally, the CI group exhibited a significantly increased CMP (+44.9% compared to baseline, p &lt; 0.0001) and a significant increase in median hearing threshold (20.4 vs. 2.5 dB SPL, p = 0.0009) compared to sham after 2 h. Intriguingly, the CI group showed significantly lower iNOS-expression levels in the organ of Corti (329.5 vs. 54.33 AU, p = 0.0003), stria vascularis (596.7 vs. 48.51 AU, p &lt; 0.0001), interdental cells (564.0 vs. 109.1 AU, p = 0.0003) and limbus fibrocytes (119.4 vs. 18.69 AU, p = 0.0286).ConclusionMechanical and NO-dependent microvascular dysfunction seem to play a pivotal role in residual hearing loss after CI electrode array insertion. This may be facilitated by the implantation associated decrease in iNOS expression. Therefore, stabilization of cochlear microcirculation could be a therapeutic strategy to preserve residual hearing.
Case report: Steroid-responsive acute chorea as first presentation of the coexistence of Moyamoya and Graves' disease
Authors: Wang Wei-Sheng , Wu Shey-Lin , Chan Wei-Chieh , Chen Yen-Chung 
Published: June 2023

BackgroundChorea is a movement disorder characterized by abrupt, rapid, and uncontrollable, random movements from one part of the body to another with motor impersistence. Sporadic chorea is rarely caused by either thyrotoxicosis or Moyamoya disease (MMD).Methods and resultsIn this case report, we describe a female patient with chorea with the rare coexistence of Graves' disease and Moyamoya disease. Tc-99m ethyl cysteinate dimer (ECD) brain perfusion single-photon emission computed tomography (SPECT) showed mild to moderate hypoperfusion in bilateral frontal and left temporal regions. After administering dexamethasone 20 mg for 5 days, her choreic movement symptoms recovered rapidly.ConclusionAlthough uncommon, thyrotoxicosis and Moyamoya disease can co-occur, especially in Asian female adults. Excessive thyroid hormones contribute to the dysregulation of neurotransmitters in basal ganglia-thalamocortical circuits. Moyamoya disease is responsible for ischemic changes affecting the excitatory–inhibitory circuits between the basal ganglia and the neocortex. Under a state of coexistence, thyrotoxicosis exaggerates cerebral metabolism, aggravating the impaired cerebral perfusion induced by Moyamoya disease. Moreover, inflammatory reactions caused by thyroid autoantibodies may also promote the progression of Moyamoya disease. In our experience, treatment with steroids may not only synergize the anti-thyroid effect but may also be a way to modulate the neurotransmitters within the basal ganglia or restore cerebral perfusion. We suggest that evaluation of the thyroid function status in Moyamoya disease is essential.
Home-based exercise training by using a smartphone app in patients with Parkinson’s disease: a feasibility study
Authors: Putzolu Martina , Manzini Virginia , Gambaro Matteo , Cosentino Carola , Bonassi Gaia , Botta Alessandro , Ravizzotti Elisa , Avanzino Laura , Pelosin Elisa , Mezzarobba Susanna 
Published: June 2023

BackgroundParkinson’s disease (PD) patients experience deterioration in mobility with consequent inactivity and worsened health and social status. Physical activity and physiotherapy can improve motor impairments, but several barriers dishearten PD patients to exercise regularly. Home-based approaches (e.g., via mobile apps) and remote monitoring, could help in facing this issue.ObjectiveThis study aimed at testing the feasibility, usability and training effects of a home-based exercise program using a customized version of Parkinson Rehab® application.MethodsTwenty PD subjects participated in a two-month minimally supervised home-based training. Daily session consisted in performing PD-specific exercises plus a walking training. We measured: (i) feasibility (training adherence), usability and satisfaction (via an online survey); (ii) safety; (iii) training effects on PD severity, mobility, cognition, and mood. Evaluations were performed at: baseline, after 1-month of training, at the end of training (T2), and at 1-month follow-up (T3).ResultsEighteen out of twenty participants completed the study without important adverse events. Participants’ adherence was 91% ± 11.8 for exercise and 105.9% ± 30.6 for walking training. Usability and satisfaction survey scored 70.9 ± 7.7 out of 80. Improvements in PD severity, mobility and cognition were found at T2 and maintained at follow-up.ConclusionThe home-based training was feasible, safe and seems to positively act on PD-related symptoms, mobility, and cognition in patients with mild to moderate stage of PD disease. Additionally, the results suggest that the use of a mobile app might increase the amount of daily physical activity in our study population. Remote monitoring and tailored exercise programs appear to be key elements for promoting exercise. Future studies in a large cohort of PD participants at different stages of disease are needed to confirm these findings.