bluuebunny/crossref_metadata_2025_split huggingface dataset:
Air exposure and cell differentiation are essential for investigation of SARS-CoV-2 entry genes in human primary airway epithelial cells in vitro
Authors: Kasper Brigitte , Yue Xiaoyang , Goldmann Torsten , Gülsen Askin , Kugler Christian , Yu Xinhua , Petersen Frank 
Published: September 2022

BackgroundIn-vitro models of differentiated primary human airway epithelial cells are a valuable tool to study severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Through the use of these models, it has been shown that the expression of SARS-CoV-2 entry genes in human airway epithelia is influenced by various factors such as age, sex, smoking status, and pathogenic conditions. In this study, we aimed to determine the effects of cell culture conditions and donor demographic and clinical characteristics on the expression of SARS-CoV-2 entry genes including angiotensin converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2), cathepsin L (CTSL), and tyrosine protein kinase receptor UFO (AXL) in primary airway epithelial cells.MethodsEleven lung cancer patients with or without chronic obstructive pulmonary disease (COPD) or asthma were recruited. Human bronchial epithelial cells (HBEC) or small airway epithelial cells (SAEC) isolated from submerged or air-liquid interface (ALI) cultures were analyzed by quantitative real-time PCR. We also tested for correlations with clinical data.ResultsIn ALI cultures, the expression of AXL was significantly higher in HBEC than in SAEC. In addition, the expression of ACE2, TMPRSS2, and CTSL was significantly increased in both HBEC and SAEC differentiated under ALI conditions compared with the submerged culture. Negligible association was found between the expression of SARS-CoV-2 entry genes in SAEC and the age, sex, smoking status, and complication of COPD, asthma or hypertension of the cell donors.ConclusionThese results demonstrate that the expression of SARS-CoV-2 entry genes in differentiated primary airway epithelial cells in-vitro is much more influenced by individual culture conditions than by specific characteristics of individual donors.
The impact and role of hepatic hydrothorax in the prognosis of patients with decompensated cirrhosis: A retrospective propensity score-matched study
Authors: Ma Bo , Shang Tianling , Huang Jianjie , Tu Zhixin , Wang Yan , Han Yujin , Wen Xiaoyu , Jin Qinglong 
Published: September 2022

Background and aimsHepatic Hydrothorax (HH) is one of the complications in patients with decompensated cirrhosis and its impact and role in the prognosis of patients with decompensated cirrhosis are not yet clear. Thus, this study aimed to determine the role of HH in patients with decompensated cirrhosis and the long-term impact on their mortality.Materials and methodsA retrospective study analyzed 624 patients with ascites without pleural effusion in decompensated cirrhosis and 113 patients with HH. Propensity scores were calculated based on eight variables, and the HH and non-HH groups were matched in a 1:1 ratio. The effect and role of HH on the prognosis of patients with decompensated cirrhosis was analyzed using the Kaplan–Meier method and Cox proportional hazards regression model.ResultsA total of 737 patients were included. Out of 113 HH patients, 106 could be matched to 106 non-HH patients. After matching, baseline characteristics were well-balanced. The multifactorial Cox proportional hazards model indicated that hepatic encephalopathy and HH were independent risk factors affecting prognostic survival in patients with decompensated cirrhosis (P &lt; 0.01), with risk ratios and 95% confidence intervals (CI) of 2.073 (95% CI: 1.229–3.494, P &lt; 0.01) and 4.724 (95% CI: 3.287–6.789, P &lt; 0.01), respectively. Prognostic survival was significantly worse in the HH group compared to patients in the non-HH group, with mortality rates of 17.9, 30.1, and 59.4% at 6 months, 1 year, and 2 years in the HH group, compared to 0.9, 3.8, and 5.6% in the non-HH group, respectively. The estimated median survival time was 21 (95% CI: 18–25) months in the HH group and 49 (95% CI: 46–52) months in the non-HH group (P &lt; 0.001).ConclusionHepatic hydrothorax is significantly associated with higher mortality in patients with decompensated cirrhosis and is a highly negligible independent decompensated event affecting their prognosis.
Anabolic-androgenic steroids for patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis
Authors: Liu Yahui , Huang Chunrong , Du Juan , Lan Gelei , Du Xueqing , Sun Yidan , Shi Guochao 
Published: September 2022

BackgroundTestosterone deficiency is common in chronic obstructive pulmonary disease (COPD) patients. There has been a growing interest in the potential use of anabolic-androgenic steroids (AASs) in patients with COPD recently. However, whether AASs could improve their clinical outcomes remains unknown.MethodsIn order to explore the efficacy of AASs in patients with COPD, systematic search of MEDLINE, Embase, the Cochrane Library and ClinicalTrials.gov for randomized controlled trials (RCTs) of AASs for COPD published before March 17, 2022 was performed.ResultsData were extracted from 8 articles involving 520 participants. The median number of participants per study was 39.5 and the mean follow up was 14.2 weeks. As compared to the control group, AASs therapy could significantly improve body weight (weighted mean difference (WMD), 1.38 kg; 95% CI, 0.79 to 1.97 kg), fat-free mass (WMD, 1.56 kg; 95% CI, 0.94 to 2.18 kg) and peak workload (WMD, 6.89W; 95% CI, 3.97 to 9.81W) of COPD patients, but no improvements in spirometry indicators and six-minute walking distances (WMD, 16.88 m; 95%, −3.27 to 37.04 m). Based on the available research data, it is uncertain whether AASs treatment could improve the quality of life of COPD patients.ConclusionsLimited published evidence indicates that AASs therapy provides clinical benefits in patients with COPD. However, longer and larger studies are needed to better clarify the efficacy of AASs and draw final conclusions.
Altered B cell phenotype and CD27+ memory B cells are associated with clinical features and environmental exposure in Colombian systemic lupus erythematosus patients
Authors: Hurtado Carolina , Rojas-Gualdrón Diego Fernando , Urrego Rodrigo , Cashman Kevin , Vásquez-Trespalacios Elsa María , Díaz-Coronado Juan Camilo , Rojas Mauricio , Jenks Scott , Vásquez Gloria , Sanz Ignacio 
Published: September 2022

BackgroundB lymphocytes are dysregulated in Systemic Lupus Erythematosus (SLE) including the expansion of extrafollicular B cells in patients with SLE of African American ancestry, which is associated with disease activity and nephritis. The population of Colombia has a mixture of European, Native American, and African ancestry. It is not known if Colombian patients have the same B cell distributions described previously and if they are associated with disease activity, clinical manifestations, and environmental exposures.ObjectiveTo characterize B cell phenotype in a group of Colombian Systemic Lupus Erythematosus patients with mixed ancestry and determine possible associations with disease activity, clinical manifestations, the DNA methylation status of the IFI44L gene and environmental exposures.Materials and methodsForty SLE patients and 17 healthy controls were recruited. Cryopreserved peripheral B lymphocytes were analyzed by multiparameter flow cytometry, and the DNA methylation status of the gene IFI44L was evaluated in resting Naive B cells (rNAV).ResultsExtrafollicular active Naive (aNAV) and Double Negative type 2, DN2 (CD27− IgD− CD21− CD11c+) B cells were expanded in severe active patients and were associated with nephritis. Patients had hypomethylation of the IFI44L gene in rNAV cells. Regarding environmental exposure, patients occupationally exposed to organic solvents had increased memory CD27+ cells (SWM).ConclusionaNAV and DN2 extrafollicular cells showed significant clinical associations in Colombian SLE patients, suggesting a relevant role in the disease’s pathophysiology. Hypomethylation of the IFI44L gene in resting Naive B cells suggests that epigenetic changes are established at exceedingly early stages of B cell ontogeny. Also, an alteration in SWM memory cells was observed for the first time in patients exposed to organic solvents. This opens different clinical and basic research possibilities to corroborate these findings and deepen the knowledge of the relationship between environmental exposure and SLE.
Relative binding free energy calculations with transformato: A molecular dynamics engine-independent tool
Authors: Karwounopoulos Johannes , Wieder Marcus , Boresch Stefan 
Published: September 2022

We present the software package transformato for the setup of large-scale relative binding free energy calculations. Transformato is written in Python as an open source project (https://github.com/wiederm/transformato); in contrast to comparable tools, it is not closely tied to a particular molecular dynamics engine to carry out the underlying simulations. Instead of alchemically transforming a ligand L1 directly into another L2, the two ligands are mutated to a common core. Thus, while dummy atoms are required at intermediate states, in particular at the common core state, none are present at the physical endstates. To validate the method, we calculated 76 relative binding free energy differences ΔΔGL1→L2bind for five protein–ligand systems. The overall root mean squared error to experimental binding free energies is 1.17 kcal/mol with a Pearson correlation coefficient of 0.73. For selected cases, we checked that the relative binding free energy differences between pairs of ligands do not depend on the choice of the intermediate common core structure. Additionally, we report results with and without hydrogen mass reweighting. The code currently supports OpenMM, CHARMM, and CHARMM/OpenMM directly. Since the program logic to choose and construct alchemical transformation paths is separated from the generation of input and topology/parameter files, extending transformato to support additional molecular dynamics engines is straightforward.
Multimodal ultrasound fusion network for differentiating between benign and malignant solid renal tumors
Authors: Zhu Dongmei , Li Junyu , Li Yan , Wu Ji , Zhu Lin , Li Jian , Wang Zimo , Xu Jinfeng , Dong Fajin , Cheng Jun 
Published: September 2022

Objective: We aim to establish a deep learning model called multimodal ultrasound fusion network (MUF-Net) based on gray-scale and contrast-enhanced ultrasound (CEUS) images for classifying benign and malignant solid renal tumors automatically and to compare the model’s performance with the assessments by radiologists with different levels of experience.Methods: A retrospective study included the CEUS videos of 181 patients with solid renal tumors (81 benign and 100 malignant tumors) from June 2012 to June 2021. A total of 9794 B-mode and CEUS-mode images were cropped from the CEUS videos. The MUF-Net was proposed to combine gray-scale and CEUS images to differentiate benign and malignant solid renal tumors. In this network, two independent branches were designed to extract features from each of the two modalities, and the features were fused using adaptive weights. Finally, the network output a classification score based on the fused features. The model’s performance was evaluated using five-fold cross-validation and compared with the assessments of the two groups of radiologists with different levels of experience.Results: For the discrimination between benign and malignant solid renal tumors, the junior radiologist group, senior radiologist group, and MUF-Net achieved accuracy of 70.6%, 75.7%, and 80.0%, sensitivity of 89.3%, 95.9%, and 80.4%, specificity of 58.7%, 62.9%, and 79.1%, and area under the receiver operating characteristic curve of 0.740 (95% confidence internal (CI): 0.70–0.75), 0.794 (95% CI: 0.72–0.83), and 0.877 (95% CI: 0.83–0.93), respectively.Conclusion: The MUF-Net model can accurately classify benign and malignant solid renal tumors and achieve better performance than senior radiologists.Key points: The CEUS video data contain the entire tumor microcirculation perfusion characteristics. The proposed MUF-Net based on B-mode and CEUS-mode images can accurately distinguish between benign and malignant solid renal tumors with an area under the receiver operating characteristic curve of 0.877, which surpasses senior radiologists’ assessments by a large margin.
Ultrasonography of abdominal muscles: Differential diagnosis of late-onset Pompe disease and myotonic dystrophy type 1
Authors: Hsieh Pei-Chen , Chang Chun-Wei , Ro Long-Sun , Huang Chin-Chang , Chi Jia-En , Kuo Hung-Chou 
Published: September 2022

IntroductionAxial muscles are involved earlier and to a greater extent in late-onset Pompe disease (LOPD) than in myotonic muscular dystrophy type 1 (DM1). We aimed to evaluate abdominal muscles in LOPD compared in DM1 using muscle ultrasonography.MethodsPatients with LOPD (n = 3), DM1 (n = 10), and age- and gender-matched healthy subjects (n = 34) were enrolled for muscle ultrasonography. Patients with LOPD and DM1 were 20 to 59 years of age with a disease duration ranging between 7 and 30 years. A multifrequency linear transducer was used to evaluate quality and thickness in the abdominal muscles and extremities.ResultsThe quantitative muscle echo score revealed a higher Z score in abdominal muscles in Patients with LOPD (scores were relatively normal for the biceps and flexor digitorum groups). Patients with LOPD had significantly lower abdominal muscle thickness than patients with DM1. Abdominal muscle strength was significantly correlated with the muscle echogenicity, trunk impairment scale, and trunk control test. The extremities' sum score was correlated with the total Medical Research Council score.DiscussionThe increased quantitative muscle score in abdominal muscles, sparing the biceps and flexor digitorum groups, may offer differential diagnosis between LOPD and DM1. Ultrasound can easily access abdominal muscles and investigate muscle echogenicity and thickness. A quantitative approach using muscle echogenicity rather than muscle thickness may provide a greater correlation with trunk muscle function.
Cerebral hemodynamic changes to transcranial Doppler sonography in celiac disease: A pilot study
Authors: Fisicaro Francesco , Lanza Giuseppe , D’Agate Carmela Cinzia , Pennisi Manuela , Cantone Mariagiovanna , Pennisi Giovanni , Hadjivassiliou Marios , Bella Rita 
Published: September 2022

BackgroundSonographic mesenteric pattern in celiac disease (CD) suggests a hyperdynamic circulation. Despite the well-known CD-related neurological involvement, no study has systematically explored the cerebral hemodynamics to transcranial Doppler sonography.Materials and methodsMontreal Cognitive Assessment (MoCA) and 17-item Hamilton Depression Rating Scale (HDRS) were assessed in 15 newly diagnosed subjects with CD and 15 age-, sex-, and education-matched healthy controls. Cerebral blood flow (CBF) velocities and indices of resistivity (RI) and pulsatility (PI) from the middle cerebral artery (MCA), bilaterally, and the basilar artery (BA) were recorded. We also assessed cerebral vasomotor reactivity (CVR) through the breath-holding test (BHT).ResultsWorse scores of MoCA and HDRS were found in patients compared to controls. Although patients showed higher values of CBF velocity from MCA bilaterally compared to controls, both at rest and after BHT, no comparison reached a statistical significance, whereas after BHT both RI and PI from BA were significantly higher in patients. A significant negative correlation between both indices from BA and MoCA score were also noted.ConclusionThese treatment-naïve CD patients may show some subtle CVR changes in posterior circulation, thus possibly expanding the spectrum of pathomechanisms underlying neuroceliac disease and in particular gluten ataxia. Subclinical identification of cerebrovascular pathology in CD may help adequate prevention and early management of neurological involvement.
Case Report: Submucosal gastroblastoma with a novel PTCH1::GLI2 gene fusion in a 58-year-old man
Authors: Chen Cuimin , Lu Junliang , Wu Huanwen 
Published: September 2022

Gastroblastoma is a rare biphasic tumor of the stomach that generally presents in young patients. MALAT1-GLI1 gene fusion was considered to be the characteristic molecular alteration of this tumor in previous reports. Herein, we described a 58-year-old man with a mass mainly located in the submucosa of the stomach. Microscopic examination showed a biphasic morphology with the same immunohistochemical phenotype as gastroblastoma. Interestingly, a novel PTCH1::GLI2 fusion rather than MALAT1-GLI1 fusion was detected in the tumor by RNA-based next generation sequencing (NGS). This was the first report that demonstrated a novel PTCH1::GLI2 gene fusion in gastroblastoma, and thus expanded the molecular spectrum of this tumor. The underlying pathogenesis merits further investigation.
Vocal nodules in children: Laryngoscopic morphological classification aids prognostic judgment
Authors: Liu Jia , Cao Wei , Sun Dan-Hua , Wu Lei , Sun Jing , Xu Bin , Fu Yong 
Published: September 2022

ObjectiveVocal fold nodules (VFNs) are benign lesions, occurring at the junction of the anterior and middle thirds of bilateral vocal cords, for which pediatric prognosis and treatment remains controversial. There is a requirement for a correlation indicator to assess the prognosis by pediatric otolaryngologists.Materials and methodsPatients with VFNs, who were admitted to the department of otolaryngology, were enrolled. The patient’s gender, age, duration of dysphonia, laryngoscopy results and related diseases [allergic rhinitis, sinusitis, laryngopharyngeal reflux (LPR)] were collected and recovery from dysphonia followed up. Correlations between clinical factors and type of laryngoscopic morphology of VFNs were analyzed.ResultsA total of 432 patients with dysphonia were identified, 208 agreed to undergo laryngoscopy and 194 were diagnosed with VFNs as a result. The modal age of patients with dysphonia was between 3 and 7 years with a male: female ratio of 2.1:1 (294:138) and 116 (26.85%; 116/432) had symptoms of allergic rhinitis. The boy to girl ratio among the 194 children with VFNs was about 2.6:1 (140:54) and modal age was consistent with dysphonia. Vocal nodules were the cause of most phonation disorders (93.27%; 194/208) and those with long duration of dysphonia presented more mature (p = 0.026) and discrete types (p = 0.022). Boys were more likely to have mature (p = 0.050) and discrete nodules (p = 0.008). Dysphonia recovery time was closely related to age (p = 0.000), duration of dysphonia (p = 0.000) and morphology of vocal nodules under laryngoscopy (p = 0.000).ConclusionVocal nodules are the most frequent cause of phonation disorders in children. The morphological classification by endoscopy may help with clinical diagnosis and therapy choice. In the case of the older child with longer duration of dysphonia and the appearance of mature, large, discrete nodules by laryngoscopy, active treatment is recommended, such as drug therapy, voice therapy or surgical treatment.
The possible association between epidemics of hand-foot-and-mouth disease and responsiveness to immunoglobulin therapy in Kawasaki disease
Authors: Shimizu Daisuke , Hoshina Takayuki , Kawamura Masaru , Tomita Yoshie , Hidaka Yasufumi , Kojiro Masumi , Muneuchi Jun , Kamizono Junji , Yamaguchi Kenichiro , Fujino Yoshihisa , Kusuhara Koichi 
Published: September 2022

BackgroundEnterovirus causing hand-foot-mouth disease (HFMD) has been reported to be associated with the development of Kawasaki disease (KD), whereas the involvement of enterovirus in the clinical course of KD is uncertain. The aim of this study is to investigate the association between the clinical course of KD and HFMD epidemics.MethodsThis study included 108 patients who developed KD during HFMD epidemic seasons (July and August) from 2010 to 2014 and who were initially treated with high-dose intravenous immunoglobulin (IVIG). A mean of ≥5.0 HFMD patients reported weekly from each sentinel medical facility was considered to represent a large HFMD epidemic. We compared the clinical characteristics of KD patients in summers of years with and without large HFMD epidemics.ResultsLarge HFMD epidemics occurred in 2011 and 2013. The number of KD patients in summer was the highest in 2011. The proportion of patients with resistance to the IVIG therapy in summers of years with the large epidemics (14%) was significantly lower than that in summers of other years (31%, P = 0.030), whereas the proportion of patients with coronary artery abnormalities did not differ to a statistically significant extent. The development of KD during large HFMD epidemics was significantly associated with a lower risk of resistance to the IVIG therapy (incidence rate ratio 0.92, P = 0.049).ConclusionPatients developing KD during large HFMD epidemic may have good responsiveness to IVIG. It is important to identify microbes from KD patients to predict responsiveness to IVIG therapy.
Can’t find the antidote: A root cause analysis
Authors: Abu Esba Laila Carolina , Mardawi Ghada , Al Deeb Mohammad 
Published: September 2022

Background: In a series of cases that came to be recognized as a national methanol outbreak, an incident of delay in allocation and treatment with the antidote fomepizole is described with aim of sharing a learning experience.Method: A team of 16 members was formed to conduct a Root Cause Analysis (RCA), which included multiple individual interviews with the stakeholders and inspection visits to the area.Results: Root causes: The restocking process was unclear and inconsistent and specifically lacked a restocking policy for antidotes, inappropriate labeling and area design, and a sound-alike between fomepizole and omeprazole. Contributing factors included: unsuitable restocking practice and lack of training in using the pharmaceutical electronic inventory system. Corrective actions were recommended and implemented.Conclusion: Management of antidotes in large healthcare systems requires a team effort to ensure appropriate and timely availability in emergency poisoning cases. This RCA identified important areas for improvement that could be insightful to other institutions in preventing similar vulnerabilities and is unique in describing the details of system improvements that can have a large impact on patient safety.