bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperoxia Provokes Time- and Dose-Dependent Gut Injury and Endotoxemia and Alters Gut Microbiome and Transcriptome in Mice
Authors: Li Yunhang , Tao Yuanfa , Xu Jingyu , He Yihuai , Zhang Wen , Jiang Zhigang , He Ying , Liu Houmei , Chen Miao , Zhang Wei , Xing Zhouxiong 
Published: November 2021

Background: Oxygen therapy usually exposes patients to hyperoxia, which induces injuries in the lung, the heart, and the brain. The gut and its microbiome play key roles in critical illnesses, but the impact of hyperoxia on the gut and its microbiome remains not very clear. We clarified the time- and dose-dependent effects of hyperoxia on the gut and investigated oxygen-induced gut dysbiosis and explored the underlying mechanism of gut injury by transcriptome analysis.Methods: The C57BL/6 mice were randomly divided into the control group and nine different oxygen groups exposed to hyperoxia with an inspired O2 fraction (FiO2) of 40, 60, and 80% for 24, 72, and 168 h (7 days), respectively. Intestinal histopathological and biochemical analyses were performed to explore the oxygen-induced gut injury and inflammatory response. Another experiment was performed to explore the impact of hyperoxia on the gut microbiome by exposing the mice to hyperoxia (FiO2 80%) for 7 days, with the 16S rRNA sequencing method. We prolonged the exposure (up to 14 days) of the mice to hyperoxia (FiO2 80%), and gut transcriptome analysis and western blotting were carried out to obtain differentially expressed genes (DEGs) and signaling pathways related to innate immunity and cell death.Results: Inhaled oxygen induced time- and dose-dependent gut histopathological impairment characterized by mucosal atrophy (e.g., villus shortening: 80% of FiO2 for 24 h: P = 0.008) and enterocyte death (e.g., apoptosis: 40% of FiO2 for 7 days: P = 0.01). Administered time- and dose-dependent oxygen led to intestinal barrier dysfunction (e.g., endotoxemia: 80% of FiO2 for 72 h: P = 0.002) and potentiated gut inflammation by increasing proinflammatory cytokines [e.g., tumor necrosis factor alpha (TNF-α): 40% of FiO2 for 24 h: P = 0.003)] and reducing anti-inflammatory cytokines [Interleukin 10 (IL-10): 80% of FiO2 for 72 h: P &lt; 0.0001]. Hyperoxia induced gut dysbiosis with an expansion of oxygen-tolerant bacteria (e.g., Enterobacteriaceae). Gut transcriptome analysis identified 1,747 DEGs and 171 signaling pathways and immunoblotting verified TLR-4, NOD-like receptor, and apoptosis signaling pathways were activated in oxygen-induced gut injury.Conclusions: Acute hyperoxia rapidly provokes gut injury in a time- and dose-dependent manner and induces gut dysbiosis, and an innate immune response is involved in an oxygen-induced gut injury.
Immunomodulatory and Anti-fibrotic Effects Following the Infusion of Umbilical Cord Mesenchymal Stromal Cells in a Critically Ill Patient With COVID-19 Presenting Lung Fibrosis: A Case Report
Authors: Silva Kátia Nunes da , Pinheiro Priscila Carvalho Guedes , Gobatto André Luiz Nunes , Passos Rogério da Hora , Paredes Bruno Diaz , França Luciana Souza de Aragão , Nonaka Carolina Kymie Vasques , Barreto-Duarte Beatriz , Araújo-Pereira Mariana , Tibúrcio Rafael , Cruz Fernanda Ferreira , Martins Gabriele Louise Soares , Andrade Bruno B. , Castro-Faria-Neto Hugo Caire de , Rocco Patricia Rieken Macêdo , Souza Bruno Solano de Freitas 
Published: November 2021

Background: The patients with coronavirus disease 2019 (COVID-19) associated with severe acute respiratory distress syndrome (ARDS) may require prolonged mechanical ventilation which often results in lung fibrosis, thus worsening the prognosis and increasing fatality rates. A mesenchymal stromal cell (MSC) therapy may decrease lung inflammation and accelerate recovery in COVID-19. In this context, some studies have reported the effects of MSC therapy for patients not requiring invasive ventilation or during the first hours of tracheal intubation. However, this is the first case report presenting the reduction of not only lung inflammation but also lung fibrosis in a critically ill long-term mechanically ventilated patient with COVID-19.Case Presentation: This is a case report of a 30-year-old male patient with COVID-19 under invasive mechanical ventilation for 14 days in the intensive care unit (ICU), who presented progressive clinical deterioration associated with lung fibrosis. The symptoms onset was 35 days before MSC therapy. The patient was treated with allogenic human umbilical-cord derived MSCs [5 × 107 (2 doses 2 days interval)]. No serious adverse events were observed during and after MSC administration. After MSC therapy, PaO2/FiO2 ratio increased, the need for vasoactive drugs reduced, chest CT scan imaging, which initially showed signs of bilateral and peripheral ground-glass, as well as consolidation and fibrosis, improved, and the systemic mediators associated with inflammation decreased. Modulation of the different cell populations in peripheral blood was also observed, such as a reduction in inflammatory monocytes and an increase in the frequency of patrolling monocytes, CD4+ lymphocytes, and type 2 classical dendritic cells (cDC2). The patient was discharged 13 days after the cell therapy.Conclusions: Mesenchymal stromal cell therapy may be a promising option in critically ill patients with COVID-19 presenting both severe lung inflammation and fibrosis. Further clinical trials could better assess the efficacy of MSC therapy in critically ill patients with COVID-19 with lung fibrosis associated with long-term mechanical ventilation.
Patient Uptake, Experiences, and Process Evaluation of a Randomized Controlled Trial of Internet-Based Cognitive Behavioral Therapy for Tinnitus in the United States
Authors: Beukes Eldre W. , Andersson Gerhard , Manchaiah Vinaya 
Published: November 2021

Introduction: An internet-based cognitive behavioral therapy (ICBT) offers a way to increase access to evidence-based tinnitus care. To increase the accessibility of this intervention, the materials were translated into Spanish to reach Spanish as well as English speakers. A clinical trial indicated favorable outcomes of ICBT for tinnitus for the population of the United States. In view of later dissemination, a way to increase the applicability of this intervention is required. Such understanding is best obtained by considering the perspectives and experiences of participants of an intervention. This study aimed to identify the processes that could facilitate or hinder the clinical implementation of ICBT in the United States.Methods: This study evaluated the processes regarding enrolment, allocation, intervention delivery, the outcomes obtained, and the trial implementation. The study sample consisted of 158 participants who were randomly assigned to the experimental and control group.Results: Although the recruitment was sufficient for English speakers, recruiting the Spanish participants and participants belonging to ethnic minority groups was difficult despite using a wide range of recruitment strategies. The allocation processes were effective in successfully randomizing the groups. The intervention was delivered as planned, but not all the participants chose to engage with the materials provided. Compliance for completing the outcome measures was low. The personal and intervention factors were identified as barriers for the implementation whereas the facilitators included the support received, being empowering, the accessibility of the intervention, and its structure.Conclusion: An understanding regarding the factors contributing to the outcomes obtained, the barriers and facilitators of the results, engagement, and compliance were obtained. These insights will be helpful in preparing for the future dissemination of such interventions.Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04004260. Registered on 2 July 2019.
Errors in Diagnosing Infectious Diseases: A Physician Survey
Authors: Haddad Mahboubeh , Sheybani Fereshte , Naderi HamidReza , Sasan Mohammad Saeed , Najaf Najafi Mona , Sedighi Malihe , Seddigh Atena 
Published: November 2021

Background: Infectious diseases are commonly missed or misdiagnosed. Errors in diagnosing infectious diseases not only affect the patient but also the community health.Objectives: To describe our investigation on the most common errors in diagnosing infectious diseases and their causes according to the physicians' reports.Methods: Between August 2018 and February 2019, specialist physicians and residents across Mashhad, Iran were invited to participate in a survey to report errors they had made or witnessed regarding the diagnosis of infectious diseases.Results: Overall, 465 cases were reported by 315 participants. The most common infectious diseases affected by diagnostic errors were upper respiratory tract infections (URTIs) (n = 69, 14.8%), tuberculosis (TB) (n = 66, 14.1%), pleuro-pulmonary infections (n = 54, 11.6%), central nervous system (CNS) infections (n = 51, 10.9%), and urinary tract infections (n = 45, 9.6%). Errors occurred most frequently in generating a diagnostic hypothesis (n = 259, 55/7%), followed by history taking (n = 200, 43%), and physical examination (n = 191, 41/1%). Errors related to the diagnosis of TB (odds ratio [OR]: 2.4, 95% confidence interval [CI]:0.9–5.7; P value: 0.047) and intra-abdominal infections (OR: 7.2, 95% CI: 0.9–53.8; P value: 0.02) were associated with more-serious outcomes.Conclusion: A substantial proportion of errors in diagnosing infectious diseases moderately or seriously affect patients' outcomes. URTIs, TB, and pleuropulmonary infections were the most frequently reported infectious diseases involved in diagnostic error while errors related to the diagnosis of TB and intraabdominal infections were more frequently associated with poor outcomes. Therefore, contagious and potentially life-threatening infectious diseases should always be considered in the differential diagnosis of patients who present with compatible clinical syndromes.
Long-Term Efficacy of Low-Intensity Single Donor Fecal Microbiota Transplantation in Ulcerative Colitis and Outcome-Specific Gut Bacteria
Authors: Ren Rongrong , Gao Xuefeng , Shi Yichao , Li Jianfeng , Peng Lihua , Sun Gang , Wang Zikai , Yan Bin , Zhi Junli , Yang Yunsheng 
Published: November 2021

Aims: To assess the long-term efficacy and safety of single-donor, low-intensity fecal microbiota transplantation (FMT) in treating ulcerative colitis (UC), and to identify the outcome-specific gut bacteria.Design: Thirty-one patients with active UC (Mayo scores ≥ 3) were recruited, and all received FMT twice, at the start of the study and 2∼3 months later, respectively, with a single donor and a long-term follow-up. The fecal microbiome profile was accessed via 16S rRNA sequencing before and after FMT.Results: After the first FMT, 22.58% (7/31) of patients achieved clinical remission and endoscopy remission, with the clinical response rate of 67.74% (21/31), which increased to 55% (11/20) and 80% (16/20), respectively, after the second FMT. No serious adverse events occurred in all patients. During 4 years of follow-up, the mean remission period of patients was 26.5 ± 19.98 m; the relapse rate in the 12 remission patients was 33.33% within 1 year, and 58.3% within 4 years. At baseline, UC patients showed an enrichment in some proinflammatory microorganisms compared to the donor, such as Bacteroides fragilis, Clostridium difficile, and Ruminococcus gnavus, and showed reduced amounts of short-chain fatty acid (SCFA) producing bacteria especially Faecalibacterium prausnitzii. FMT induced taxonomic compositional changes in the recipient gut microbiota, resulting in a donor-like state. Given this specific donor, UC recipients with different outcomes showed distinct gut microbial features before and after FMT. In prior to FMT, relapse was characterized by higher abundances of Bacteroides fragilis and Lachnospiraceae incertae sedis, together with lower abundances of Bacteroides massiliensis, Roseburia, and Ruminococcus; Prevotella copri was more abundant in the non-responders (NR); and the patients with sustained remission (SR) had a higher abundance of Bifidobacterium breve. After FMT, the NR patients had a lower level of Bifidobacterium compared to those with relapse (Rel) and SR, while a higher level of Bacteroides spp. was observed in the Rel group.Conclusion: Low-intensity single donor FMT could induce long remission in active UC. The gut microbiota composition in UC patients at baseline may be predictive of therapeutic response to FMT.
A Novel Approach Using FDG-PET/CT-Based Radiomics to Assess Tumor Immune Phenotypes in Patients With Non-Small Cell Lung Cancer
Authors: Zhou Jianyuan , Zou Sijuan , Kuang Dong , Yan Jianhua , Zhao Jun , Zhu Xiaohua 
Published: November 2021

PurposeTumor microenvironment immune types (TMITs) are closely related to the efficacy of immunotherapy. We aimed to assess the predictive ability of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT)-based radiomics of TMITs in treatment-naive patients with non-small cell lung cancer (NSCLC).MethodsA retrospective analysis was performed in 103 patients with NSCLC who underwent 18F-FDG PET/CT scans. The patients were randomly assigned into a training set (n = 71) and a validation set (n = 32). Tumor specimens were analyzed by immunohistochemistry for the expression of programmed death-ligand 1 (PD-L1), programmed death-1 (PD-1), and CD8+ tumor-infiltrating lymphocytes (TILs) and categorized into four TMITs according to their expression of PD-L1 and CD8+ TILs. LIFEx package was used to extract radiomic features. The optimal features were selected using the least absolute shrinkage and selection operator (LASSO) algorithm, and a radiomics signature score (rad-score) was developed. We constructed a combined model based on the clinical variables and radiomics signature and compared the predictive performance of models using receiver operating characteristic (ROC) curves.ResultsFour radiomic features (GLRLM_LRHGE, GLZLM_SZE, SUVmax, NGLDM_Contrast) were selected to build the rad-score. The rad-score showed a significant ability to discriminate between TMITs in both sets (p &lt; 0.001, p &lt; 0.019), with an area under the ROC curve (AUC) of 0.800 [95% CI (0.688–0.885)] in the training set and that of 0.794 [95% CI (0.615–0.916)] in the validation set, while the AUC values of clinical variables were 0.738 and 0.699, respectively. When clinical variables and radiomics signature were combined, the complex model showed better performance in predicting TMIT-I tumors, with the AUC values increased to 0.838 [95% CI (0.731–0.914)] in the training set and 0.811 [95% CI (0.634–0.927)] in the validation set.ConclusionThe FDG-PET/CT-based radiomic features showed good performance in predicting TMIT-I tumors in NSCLC, providing a promising approach for the choice of immunotherapy in a clinical setting.
Effectiveness and Toxicity of Fractionated Proton Beam Radiotherapy for Cranial Nerve Schwannoma Unsuitable for Stereotactic Radiosurgery
Authors: Eichkorn Tanja , Regnery Sebastian , Held Thomas , Kronsteiner Dorothea , Hörner-Rieber Juliane , El Shafie Rami A. , Herfarth Klaus , Debus Jürgen , König Laila 
Published: November 2021

PurposeIn this benign tumor entity, preservation of cranial nerve function is of special importance. Due to its advantageous physical properties, proton beam radiotherapy (PRT) is a promising approach that spares healthy tissue. Could PRT go along with satisfactory preservation rates for cranial nerve function without compromising tumor control in patients with cranial nerve schwannoma unsuitable for stereotactic radiosurgery?MethodsWe analyzed 45 patients with cranial nerve schwannomas who underwent PRT between 2012 and 2020 at our institution. Response assessment was performed by MRI according to RECIST 1.1, and toxicity was graded following CTCAE 5.0.ResultsThe most common schwannoma origin was the vestibulocochlear nerve with 82.2%, followed by the trigeminal nerve with 8.9% and the glossopharyngeal nerve as well as the vagal nerve, both with each 4.4%. At radiotherapy start, 58% of cranial nerve schwannomas were progressive and 95.6% were symptomatic. Patients were treated with a median total dose of 54 Gy RBE in 1.8 Gy RBE per fraction. MRI during the median follow-up period of 42 months (IQR 26–61) revealed stable disease in 93.3% of the patients and partial regression in 6.7%. There was no case of progressive disease. New or worsening cranial nerve dysfunction was found in 20.0% of all patients, but always graded as CTCAE °I-II. In seven cases (16%), radiation-induced contrast enhancements (RICE) were detected after a median time of 14 months (range 2–26 months). RICE were asymptomatic (71%) or transient symptomatic (CTCAE °II; 29%). No CTCAE °III/IV toxicities were observed. Lesions regressed during the follow-up period in three of the seven cases, and no lesion progressed during the follow-up period.ConclusionThese data demonstrate excellent effectiveness with 100% local control in a median follow-up period of 3.6 years with a promising cranial nerve functional protection rate of 80%. RICE occurred in 16% of the patients after PRT and were not or only mildly symptomatic.
PSMA PET Imaging in Glioblastoma: A Preclinical Evaluation and Theranostic Outlook
Authors: Kirchner Maximilian A. , Holzgreve Adrien , Brendel Matthias , Orth Michael , Ruf Viktoria C. , Steiger Katja , Pötter Dennis , Gold Lukas , Unterrainer Marcus , Mittlmeier Lena M. , Barci Enio , Kälin Roland E. , Glass Rainer , Lindner Simon , Kaiser Lena , Maas Jessica , von Baumgarten Louisa , Ilhan Harun , Belka Claus , Notni Johannes , Bartenstein Peter , Lauber Kirsten , Albert Nathalie L. 
Published: November 2021

BackgroundProstate specific membrane antigen (PSMA) PET imaging has recently gained attention in glioblastoma (GBM) patients as a potential theranostic target for PSMA radioligand therapy. However, PSMA PET has not yet been established in a murine GBM model. Our goal was to investigate the potential of PSMA PET imaging in the syngeneic GL261 GBM model and to give an outlook regarding the potential of PMSA radioligand therapy in this model.MethodsWe performed an 18F-PSMA-1007 PET study in the orthotopic GL261 model (n=14 GBM, n=7 sham-operated mice) with imaging at day 4, 8, 11, 15, 18 and 22 post implantation. Time-activity-curves (TAC) were extracted from dynamic PET scans (0-120 min p. i.) in a subset of mice (n=4 GBM, n=3 sham-operated mice) to identify the optimal time frame for image analysis, and standardized-uptake-values (SUV) as well as tumor-to-background ratios (TBR) using contralateral normal brain as background were calculated in all mice. Additionally, computed tomography (CT), ex vivo and in vitro18F-PSMA-1007 autoradiographies (ARG) were performed.ResultsTAC analysis of GBM mice revealed a plateau of TBR values after 40 min p. i. Therefore, a 30 min time frame between 40-70 min p. i. was chosen for PET quantification. At day 15 and later, GBM mice showed a discernible PSMA PET signal on the inoculation site, with highest TBRmean in GBM mice at day 18 (7.3 ± 1.3 vs. 1.6 ± 0.3 in shams; p=0.024). Ex vivo ARG confirmed high tracer signal in GBM compared to healthy background (TBRmean 26.9 ± 10.5 vs. 1.6 ± 0.7 in shams at day 18/22 post implantation; p=0.002). However, absolute uptake values in the GL261 tumor remained low (e.g., SUVmean 0.21 ± 0.04 g/ml at day 18) resulting in low ratios compared to dose-relevant organs (e.g., mean tumor-to-kidney ratio 1.5E-2 ± 0.5E-2).ConclusionsAlthough 18F-PSMA-1007 PET imaging of GL261 tumor-bearing mice is feasible and resulted in high TBRs, absolute tumoral uptake values remained low and hint to limited applicability of the GL261 model for PSMA-directed therapy studies. Further investigations are warranted to identify suitable models for preclinical evaluation of PSMA-targeted theranostic approaches in GBM.
Challenges Faced by Emergency Physicians in China: An Observation From the Perspective of Burnout
Authors: Yan Shijiao , Shen Xin , Wang Rixing , Luo Zhiqian , Han Xiaotong , Gan Yong , Lv Chuanzhu 
Published: November 2021

Background: Burnout is considered a global problem, particularly in the emergency health sector; however, no large-sample cross-sectional study has assessed the prevalence of burnout among emergency physicians and its associated factors.Methods: A nationally representative cross-sectional survey of 15,243 emergency physicians was conducted in 31 provinces across China between July and September 2019. Multiple linear regression analysis was performed to identify correlates of burnout.Results: The participants' mean scores were 25.8 (SD = 15.9) on the emotional exhaustion (EE) subscale, 8.1 (SD = 7.9) on the depersonalization (DP) subscale, and 26.80 (SD = 12.5) on the personal accomplishment (PA) subscale, indicating a pattern of moderate EE, moderate DP, and high PA. The results of the large-sample survey found that 14.9% of emergency physicians had a high level of burnout in China, with 46.8% scoring high for EE, 24.1% scoring high for DP, and 60.5% having a high risk of low PA. Having poor self-perceived health status and sleep quality, working in developed regions and governmental hospitals, having an intermediate professional title, experiencing depression, performing shift work and experiencing workplace violence made emergency physicians more likely to experience occupational burnout.Conclusion: Positive measures should be taken to reduce the burnout of emergency physicians and improve their work enthusiasm to maintain the quality of emergency medical services.
Psychometrics of Persian Version of the Ageism Survey Among an Iranian Older Adult Population During COVID-19 Pandemic
Authors: Sharif Nia Hamid , She Long , Rasiah Ratneswary , Khoshnavay Fomani Fatemeh , Kaveh Omolhoda , Pahlevan Sharif Saeed , Hosseini Lida 
Published: November 2021

Background: Studies have revealed an increase in discrimination, neglect, and abuse among the older adult population during this period. This study assessed the validity and reliability of the Persian version of the ageism survey instrument tested on a sample of the Iranian older adult population during coronavirus disease (COVID-19) pandemic. An important move in counteracting ageism is to classify the ageism scale comprehensively by employing adequate psychometrics.Methods: The Persian version of the ageism scale was developed using a two-step procedure. The first step involved translating and revising the original scale to develop a Persian version of the ageism scale. The second step involved assessing the psychometric features of the newly adapted scale using construct validity through exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) and thereafter assessing the reliability through the average inter-item correlation (AIC), Cronbach's alpha. The sample consisted of 400 older adults (age 65 and older), who were recruited through online data collection, with samples for EFA and CFA randomly selected from the total samples.Results: The Persian version of the ageism survey has three factors: age-related deprivation with five items, dignity with three items, and employment with three items; all of which explained 57.02% of the total variance. The outcome of the EFA was verified by the CFA, with internal consistency reliability being excellent (Cronbach's alpha was 0.725, 0.698, and 0.708 for the three factors).Conclusion: This study specifically offers a restructured three factors Persian version of the ageism survey for Iranian older adults with acceptable construct validity and reliability.