bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glutathione Transferases as Efficient Ketosteroid Isomerases
Authors: Mannervik Bengt , Ismail Aram , Lindström Helena , Sjödin Birgitta , Ing Nancy H. 
Published: November 2021

In addition to their well-established role in detoxication, glutathione transferases (GSTs) have other biological functions. We are focusing on the ketosteroid isomerase activity, which appears to contribute to steroid hormone biosynthesis in mammalian tissues. A highly efficient GST A3-3 is present in some, but not all, mammals. The alpha class enzyme GST A3-3 in humans and the horse shows the highest catalytic efficiency with kcat/Km values of approximately 107 M−1s−1, ranking close to the most active enzymes known. The expression of GST A3-3 in steroidogenic tissues suggests that the enzyme has evolved to support the activity of 3β-hydroxysteroid dehydrogenase, which catalyzes the formation of 5-androsten-3,17-dione and 5-pregnen-3,20-dione that are substrates for the double-bond isomerization catalyzed by GST A3-3. The dehydrogenase also catalyzes the isomerization, but its kcat of approximately 1 s−1 is 200-fold lower than the kcat values of human and equine GST A3-3. Inhibition of GST A3-3 in progesterone-producing human cells suppress the formation of the hormone. Glutathione serves as a coenzyme contributing a thiolate as a base in the isomerase mechanism, which also involves the active-site Tyr9 and Arg15. These conserved residues are necessary but not sufficient for the ketosteroid isomerase activity. A proper assortment of H-site residues is crucial to efficient catalysis by forming the cavity binding the hydrophobic substrate. It remains to elucidate why some mammals, such as rats and mice, lack GSTs with the prominent ketosteroid isomerase activity found in certain other species. Remarkably, the fruit fly Drosophila melanogaster, expresses a GSTE14 with notable steroid isomerase activity, even though Ser14 has evolved as the active-site residue corresponding to Tyr9 in the mammalian alpha class.
The Association of Olfactory Dysfunction With Depression, Cognition, and Disease Severity in Parkinson's Disease
Authors: Fang Ting-Chun , Chang Ming-Hong , Yang Chun-Pai , Chen Yi-Huei , Lin Ching-Heng 
Published: November 2021

Background: Non-motor subtypes of Parkinson's disease (PD) include the limbic, cognitive, and brainstem phenotype, which may have different pathological pathways with olfaction. In this work, we aim to clarify the association between olfactory dysfunction, depression, cognition, and disease severity in PD.Methods: A total of 105 PD subjects were included and divided into anosmia and non-anosmic groups, using the University of Pennsylvania Smell Identification Test (UPSIT). All patients were evaluated with the movement disorder society unified Parkinson's disease rating scale (MDS-UPDRS), the Beck depression inventory (BDI)-II, and the Montreal cognitive assessment (MoCA).Results: The BDI-II and UPSIT scores had a trend of reverse correlation without statistical significance (β-coefficient −0.12, p = 0.232). However, the odds ratio (OR) in anosmia was 2.74 (95% CI 1.01–7.46) for depression and 2.58 (95% CI 1.06–6.29) for cognitive impairment. For the MDS-UPDRS total and Part 3 score, the anosmia had a β-coefficient of 12.26 (95% CI 5.69–18.82) and 8.07 (95% CI 3.46–12.67), respectively. Neither depression nor cognitive impairment is associated with motor symptoms.Conclusion: More severe olfactory dysfunction in PD is associated with cognitive impairment and greater disease severity. Depression in PD may involve complex pathways, causing relatively weak association with olfactory dysfunction.
Distribution of Immune Cells Including Macrophages in the Human Cochlea
Authors: Liu Wei , Danckwardt-Lillieström Niklas , Schrott-Fischer Anneliese , Glueckert Rudolf , Rask-Andersen Helge 
Published: November 2021

Background: The human cochlea was earlier believed to lack capacity to mount specific immune responses. Recent studies established that the human cochlea holds macrophages. The cells appear to surveil, dispose of, and restore wasted cells to maintain tissue integrity. Macrophage activities are believed to be the central elements in immune responses and could swiftly defuse invading microbes that enter via adjacent infection-prone areas. This review updates recent human studies in light of the current literature and adds information about chemokine gene expression.Materials and Methods: We analyzed surgically obtained human tissue using immunohistochemistry, confocal microscopy, and multichannel super-resolution structured illumination microscopy. The samples were considered representative of steady-state conditions. Antibodies against the ionized calcium-binding adaptor molecule 1 were used to identify the macrophages. CD68 and CD11b, and the major histocompatibility complex type II (MHCII) and CD4 and CD8 were analyzed. The RNAscope technique was used for fractalkine gene localization.Results: Many macrophages were found around blood vessels in the stria vascularis but not CD4 and CD8 lymphocytes. Amoeboid macrophages were identified in the spiral ganglion with surveilling “antennae” projecting against targeted cells. Synapse-like contacts were seen on spiral ganglion cell bodies richly expressing single CXC3CL gene transcripts. Branching neurite-like processes extended along central and peripheral axons. Active macrophages were occasionally found near degenerating hair cells. Some macrophage-interacting T lymphocytes were observed between the scala tympani wall and Rosenthal's canal. CD4 and CD8 cells were not found in the organ of Corti.Conclusions: The results indicate that the human cochlea is equipped with macrophages and potentially lymphocytes, suggesting both an innate and adaptive immune capacity. A rich expression of fractalkine gene transcripts in spiral ganglion neurons suggest an essential role for auditory nerve protection, as has been demonstrated experimentally. The findings provide further information on the important role of the immune machinery present in the human inner ear and its potential to carry adverse immune reactions, including cytotoxic and foreign body responses. The results can be used to form a rationale for therapies aiming to modulate these immune activities.
Radiomics for the Prediction of Epilepsy in Patients With Frontal Glioma
Authors: Gao Ankang , Yang Hongxi , Wang Yida , Zhao Guohua , Wang Chenglong , Wang Haijie , Zhang Xiaonan , Zhang Yong , Cheng Jingliang , Yang Guang , Bai Jie 
Published: November 2021

ObjectiveThis study was conducted in order to investigate the association between radiomics features and frontal glioma-associated epilepsy (GAE) and propose a reliable radiomics-based model to predict frontal GAE.MethodsThis retrospective study consecutively enrolled 166 adult patients with frontal glioma (111 in the training cohort and 55 in the testing cohort). A total 1,130 features were extracted from T2 fluid-attenuated inversion recovery images, including first-order statistics, 3D shape, texture, and wavelet features. Regions of interest, including the entire tumor and peritumoral edema, were drawn manually. Pearson correlation coefficient, 10-fold cross-validation, area under curve (AUC) analysis, and support vector machine were adopted to select the most relevant features to build a clinical model, a radiomics model, and a clinical–radiomics model for GAE. The receiver operating characteristic curve (ROC) and AUC were used to evaluate the classification performance of the models in each cohort, and DeLong’s test was used to compare the performance of the models. A two-sided t-test and Fisher’s exact test were used to compare the clinical variables. Statistical analysis was performed using SPSS software (version 22.0; IBM, Armonk, New York), and p &lt;0.05 was set as the threshold for significance.ResultsThe classification accuracy of seven scout models, except the wavelet first-order model (0.793) and the wavelet texture model (0.784), was &lt;0.75 in cross-validation. The clinical–radiomics model, including 17 magnetic resonance imaging-based features selected among the 1,130 radiomics features and two clinical features (patient age and tumor grade), achieved better discriminative performance for GAE prediction in both the training [AUC = 0.886, 95% confidence interval (CI) = 0.819–0.940] and testing cohorts (AUC = 0.836, 95% CI = 0.707–0.937) than the radiomics model (p = 0.008) with 82.0% and 78.2% accuracy, respectively.ConclusionRadiomics analysis can non-invasively predict GAE, thus allowing adequate treatment of frontal glioma. The clinical–radiomics model may enable a more precise prediction of frontal GAE. Furthermore, age and pathology grade are important risk factors for GAE.
Surgical Treatment and Clinical Outcomes of Petroclival Meningiomas: A Single-Center Experience of 107 Patients
Authors: Gao Baocheng , Zhang Yongfa , Tan Jiang , Ouyang Jinsong , Tai Bai , Cao Xianbao , Li Tao , Hu Shuang 
Published: November 2021

ObjectiveThis study aimed to establish optimal surgical strategies via reviewing the clinical outcomes of various surgical approaches for the pertroclival meningiomas (PCMs).MethodsThis retrospective study enrolled 107 patients with PCMs at the authors’ institution from year 2010 to 2020. Patient demographics, the clinical characteristics, various operative approaches, major morbidity, post-operative cranial nerve deficits and tumor progression or recurrence were analyzed.ResultsThe subtemporal transtentorial approach (STA), the Kawase approach (KA), the retrosigmoid approach (RSA) and the anterior sigmoid approach (ASA), namely the posterior petrosal approach (PPA) were adopted for 17 cases, 22 cases, 31 cases and 34 cases respectively. Total or subtotal resection was achieved in 96 cases (89.7%). The incidence of new-onset and aggravated cranial nerve dysfunction were 13.1% (14/107) and 10.4% (15/144), respectively. Furthermore, 14 cases suffered from intracranial infection, 9 cases had cerebrospinal fluid leakage, and 3 cases sustained intracranial hematoma (1 case underwent second operation). The mean preoperative and postoperative Karnofsky Performance Status (KPS) score was 80 (range 60-100) and 78.6 (range 0-100), but this was not statistically significant (P&gt;0.05). After a mean follow-up of 5.1 years (range 0.3- 10.6 years), tumor progression or recurrence was confirmed in 23 cases. Two cases died from postoperative complications.ConclusionsFor the treatment of PCMs, it is still a challenge to achieve total resection. With elaborate surgical plans and advanced microsurgical skills, most patients with PCMs can be rendered tumor resection with satisfactory extent and functional preservation, despite transient neurological deterioration during early postoperative periods.
Positive Reciprocal Feedback of lncRNA ZEB1-AS1 and HIF-1α Contributes to Hypoxia-Promoted Tumorigenesis and Metastasis of Pancreatic Cancer
Authors: Jin Yan , Zhang Zhengming , Yu Qiao , Zeng Zhu , Song Hong , Huang Xiaoxu , Kong Qi , Hu Hao , Xia Yabin 
Published: November 2021

BackgroundMany studies have reported the roles of the extracellular hypoxia microenvironment in the tumorigenesis and metastasis of multiple cancers. However, long noncoding RNAs (lncRNAs) that induce cancer oncogenicity and metastasis of pancreatic cancer (PC) under hypoxia conditions remain unclear.MethodsIn PC cells, the expression levels of lncRNAs in different conditions (normoxia or hypoxia) were compared through RNA sequencing (RNA-seq). The effects of the zinc finger E-box-binding homeobox 1 (ZEB1-AS1) antisense lncRNA on PC cells cultured in normoxia/hypoxia medium were measured through gain and loss-of-function experiments. Fluorescence in situ hybridization and luciferase reporter assays in addition to in vivo studies were utilized to explore the adaptive mechanisms of ZEB1-AS1 in the hypoxia-promoted proliferation, migration, and invasion ability of PC cells. Moreover, the level of ZEB1-AS1 and its associated targets or pathways were investigated in both PC and pancreatic normal tissues.ResultsRNA-seq revealed that ZEB1-AS1 was significantly upregulated in PC cells under hypoxia conditions. The ZEB1-AS1 expression level was closely associated with poor prognosis of PC patients. Knockdown of ZEB1-AS1 suppressed the proliferation, migration, and invasion of PC cells in vitro as well as PC xenograft tumor growth in vivo. In PC cells, RNAi-mediated reduction of ZEB1-AS1 inhibited zinc finger E-box-binding homeobox 1 (ZEB1), while ZEB1-AS1 overexpression rescued ZEB1 expression, indicating that ZEB1-AS1 promotes ZEB1 expression. Moreover, hypoxia-inducible factor-1α (HIF-1α)induced the expression of ZEB1-AS1 by binding to the ZEB1-AS1 promoter, which contains a putative hypoxia response element (HRE). Mechanistically, ZEB1-AS1 scaffolded the interaction among HIF-1α, ZEB1, and histone deacetylase 1 (HDAC1), leading to deacetylation-mediated stabilization of HIF-1α. We further revealed that ZEB1 induced the deacetylase capacity of HDAC1 to suppress the acetylation or degradation of HIF-1α, improving HIF-1α assembly. Thus, hypoxia-induced ZEB1-AS1 facilitated ZEB1 transcription and the stability of HIF-1α, which promoted the metastasis of PC cells. Clinically, dysregulated ZEB1 and HIF-1α expression was significantly correlated with histological grade, lymphatic metastasis, and distant metastasis in PC patients.ConclusionsOur results emphasized that the positive reciprocal loop of HIF-1α/ZEB1-AS1/ZEB1/HDAC1 contributes to hypoxia-promoted oncogenicity and PC metastasis, indicating that it might be a novel therapeutic target for PC.
Managing Severe Dysgeusia and Dysosmia in Lung Cancer Patients: A Systematic Scoping Review
Authors: Spencer Ana Sofia , da Silva Dias David , Capelas Manuel Luís , Pimentel Francisco , Santos Teresa , Neves Pedro Miguel , Mäkitie Antti , Ravasco Paula 
Published: November 2021

IntroductionLung cancer (LC) is highly prevalent worldwide, with elevated mortality. In this population, taste and smell alterations (TSAs) are frequent but overlooked symptoms. The absence of effective therapeutic strategies and evidence-based guidelines constrain TSAs’ early recognition, prevention and treatment (Tx), promoting cancer-related malnutrition and jeopardizing survival outcomes and quality of life.ObjectivesTo systematically review the literature on TSAs in LC patients, understand the physiopathology, identify potential preventive and Tx strategies and to further encourage research in this area.MethodsLiterature search on English language articles indexed to PubMed, CINALH, SCOPUS and Web of Science using MeSH terms “Lung neoplasms”,”Dysgeusia”, “Olfaction Disorders”, “Carcinoma, Small Cell”,”Carcinoma, Non- Small-Cell Lung “Adenocarcinoma of Lung”,”Carcinoma, Large Cell”, and non-MeSH terms “Parageusia”, “Altered Taste”, “Smell Disorder”, “Paraosmia”, “Dysosmia”,”Lung Cancer” and “Oat Cell Carcinoma”.ResultsThirty-four articles were reviewed. TSAs may follow the diagnosis of LC or develop during cancer Tx. The estimated prevalence of self-reported dysgeusia is 35-38% in treatment-naïve LC patients, and 35-69% in those undergoing Tx, based on studies involving LC patients only.One prospective pilot trial and 1 RCT demonstrated a clinically significant benefit in combining flavor enhancement, smell and taste training and individualized nutritional counselling; a systematic review, 1 RCT and 1 retrospective study favored using intravenous or oral zinc-based solutions (150mg 2-3 times a day) for the prevention and Tx of chemotherapy (CT) and radiotherapy (RT) -induced mucositis and subsequent dysgeusia.ConclusionsThis is the first review on dysgeusia and dysosmia in LC patients to our knowledge. We propose combining taste and smell training, personalized dietary counselling and flavor enhancement with oral zinc-based solutions (150mg, 2-3 times a day) during CT and/or RT in this population, in order to prevent and help ameliorate Tx-induced dysgeusia and mucositis. However due to study heterogeneity, the results should be interpreted with caution. Developing standardized TSA measurement tools and performing prospective randomized controlled trials to evaluate their effect are warranted.
Prognostic Value of Preoperative Peak Expiratory Flow to Predict Postoperative Pulmonary Complications in Surgical Lung Cancer Patients
Authors: Chang Shuai , Zhou Kun , Wang Yan , Lai Yutian , Che Guowei 
Published: November 2021

ObjectivesCough impairment may lead to excessive accumulation of pulmonary secretions and increase the risk of postoperative pulmonary complications (PPCs). Peak expiratory flow (PEF) is a sensitive indicator of cough ability. We aimed to investigate the correlation between PEF and PPCs for lung cancer patients undergoing lobectomy or segmental resection for improved risk assessment.MethodsThis retrospective study assessed 560 patients with non-small cell lung cancer admitted for surgery between January 2014 to June 2016. The measurements of PEF were performed before surgery and the clinical outcomes were recorded, including PPCs, postoperative hospital stay, hospitalization costs, and other variables.ResultsPreoperative PEF was significantly lower in PPCs group compared to non-PPCs group (294.2 ± 95.7 vs. 363.0 ± 105.6 L/min, P &lt; 0.001). Multivariable regression analysis showed that high PEF (OR=0.991, 95%CI: 0.988-0.993, P &lt; 0.001) was an independent protective factor for PPCs. According to the receiver operating characteristic (ROC) curve, a PEF value of 250 L/min was selected as the optimal cutoff value in female patients, and 320 L/min in male patients. Patients with PEF under cutoff value of either sex had higher PPCs rate and unfavorable clinical outcomes.ConclusionsPreoperative PEF was found to be a significant predictor of PPCs for surgical lung cancer patients. It may be beneficial to consider the cutoff value of PEF in perioperative risk assessment.
Impact of Co-occurring Mental Disorders and Chronic Physical Illnesses on Frequency of Emergency Department Use and Hospitalization for Mental Health Reasons
Authors: Gentil Lia , Grenier Guy , Meng Xiangfei , Fleury Marie-Josée 
Published: November 2021

Background: Patients with mental disorders (MD) are at high risk for a wide range of chronic physical illnesses (CPI), often resulting in greater use of acute care services. This study estimated risk of emergency department (ED) use and hospitalization for mental health (MH) reasons among 678 patients with MD and CPI compared to 1,999 patients with MD only.Methods: Patients visiting one of six Quebec (Canada) ED for MH reasons and at onset of a MD in 2014–15 (index year) were included. Negative binomial models comparing the two groups estimated risk of ED use and hospitalization at 12-month follow-up to index ED visit, controlling for clinical, sociodemographic, and service use variables.Results: Patients with MD, more severe overall clinical conditions and those who received more intensive specialized MH care had higher risks of frequent ED use and hospitalization. Continuity of medical care protected against both ED use and hospitalization, while general practitioner (GP) consultations protected against hospitalization only. Patients aged 65+ had lower risk of ED use, whereas risk of hospitalization was higher for the 45–64- vs. 12–24-year age groups, and for men vs. women.Conclusion: Strategies including assertive community treatment, intensive case management, integrated co-occurring treatment, home treatment, and shared care may improve adequacy of care for patients with MD-CPI, as well as those with MD only whose clinical profiles were severe. Prevention and outreach strategies may also be promoted, especially among men and older age groups.
SARS-CoV-2 Positive and Isolated at Home: Stress and Coping Depending on Psychological Burden
Authors: Kowalski Elias , Schneider Axel , Zipfel Stephan , Stengel Andreas , Graf Johanna 
Published: November 2021

Objective: The SARS-CoV-2 pandemic has led to pronounced health changes, especially for those infected and psychologically burdened. This cross-sectional study examined the stress experience and coping strategies during home isolation of SARS-CoV-2 infected individuals and analyzed differences regarding psychological burden.Methods: SARS-CoV-2 infected respondents were recruited by telephone and completed an online survey during their home isolation. This questionnaire assessed sociodemographic aspects, somatic factors, psychological burden (depressive symptoms, anxiety, and somatic symptom disorder), perceived stress and coping behavior during the home isolation.Results: Out of 838 SARS-CoV-2 infected individuals during the study period, 648 were contacted and 224 home-isolated respondents were included in the study. Disgrace, social restrictions, job fear, health concerns, and infectiousness could be explored as stressors during the home isolation. Fifty-four percent experienced psychological burden. SARS-CoV-2 infected and home-isolated individuals with psychological burden perceived significant stressors more strongly (p &lt; 0.001, r = 0.5) and coped significantly less (p &lt; 0.001, r = 0.3) with their infection and home isolation compared to SARS-CoV-2 infected individuals without psychological burden.Conclusion: SARS-CoV-2 infected individuals with psychological burden experienced higher stressors and were unable to cope adaptively with home isolation. Therefore, a general and standardized screening procedure for psychological burden should be established. SARS-CoV-2 infected individuals with psychological burden should receive targeted support with professional help in the areas of stress experience and coping skills during their home isolation and beyond to avoid long-term consequences.
Practical Application of QR Code Electronic Manuals in Equipment Management and Training
Authors: Ma Lifang , Mu Yonghong , Wei Ling , Wang Xiumei 
Published: November 2021

Objective: To explore the application value of QR code electronic manuals in operating theater equipment management and training.Methods: The control group adopted the traditional management mode. Training was carried out before each device was put into use in the department. A unified operation process and a paper card manual for common faults were formulated and hung next to each device. For the observation group, the electronic manuals generated by the QR code were pasted on the operating theater equipment for management and training. The management and training effect was compared between the two groups.Results: The efficiency of equipment management and training using the QR code electronic manuals was significantly higher than that of traditional training, and the difference was statistically significant (P &lt; 0.05).Conclusion: The QR code manuals are very effective in operating theater equipment management and training. They can be read and learned in time to improve the operating theater equipment utilization rate, accuracy rate, and equipment management and training quality.