bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutation in Irf8 Gene (Irf8R294C) Impairs Type I IFN-Mediated Antiviral Immune Response by Murine pDCs
Authors: Das Annesa , Chauhan Kuldeep Singh , Kumar Himanshu , Tailor Prafullakumar
Published: November 2021

Plasmacytoid dendritic cells (pDCs) are the key producers of type I interferons (IFNs), thus playing a central role in initiating antiviral immune response. Besides robust type I IFN production, pDCs also act as antigen presenting cells post immunogenic stimulation. Transcription factor Irf8 is indispensable for the development of both pDC and cDC1 subset. However, the mechanism underlying the differential regulation by IRF8 in cDC1- and pDC-specific genomic architecture of developmental pathways still remains to be fully elucidated. Previous studies indicated that the Irf8R294C mutation specifically abrogates development of cDC1 without affecting that of pDC. In the present study using RNA-seq based approach, we have found that though the point mutation Irf8R294C did not affect pDC development, it led to defective type I IFN production, thus resulting in inefficient antiviral response. This observation unraveled the distinctive roles of IRF8 in these two subpopulations—regulating the development of cDC1 whereas modulating the functionality of pDCs without affecting development. We have reported here that Irf8R294C mutation also caused defect in production of ISGs as well as defective upregulation of costimulatory molecules in pDCs in response to NDV infection (or CpG stimulation). Through in vivo studies, we demonstrated that abrogation of type I IFN production was concomitant with reduced upregulation of costimulatory molecules in pDCs and increased NDV burden in IRF8R294C mice in comparison with wild type, indicating inefficient viral clearance. Further, we have also shown that Irf8R294C mutation abolished the activation of type I IFN promoter by IRF8, justifying the low level of type I IFN production. Taken together, our study signifies that the single point mutation in Irf8, Irf8R294C severely compromised type I IFN-mediated immune response by murine pDCs, thereby causing impairment in antiviral immunity.
Potential Association Between Dietary Fibre and Humoral Response to the Seasonal Influenza Vaccine
Authors: Cait Alissa , Mooney Anna , Poyntz Hazel , Shortt Nick , Jones Angela , Gestin Aurélie , Gell Katie , Grooby Alix , O’Sullivan David , Tang Jeffry S. , Young Wayne , Thayabaran Darmiga , Sparks Jenny , Ostapowicz Tess , Tay Audrey , Poppitt Sally D. , Elliott Sarah , Wakefield Georgia , Parry-Strong Amber , Ralston Jacqui , Beasley Richard , Weatherall Mark , Braithwaite Irene , Forbes-Blom Elizabeth , Gasser Olivier
Published: November 2021

Influenza vaccination is an effective public health measure to reduce the risk of influenza illness, particularly when the vaccine is well matched to circulating strains. Notwithstanding, the efficacy of influenza vaccination varies greatly among vaccinees due to largely unknown immunological determinants, thereby dampening population-wide protection. Here, we report that dietary fibre may play a significant role in humoral vaccine responses. We found dietary fibre intake and the abundance of fibre-fermenting intestinal bacteria to be positively correlated with humoral influenza vaccine-specific immune responses in human vaccinees, albeit without reaching statistical significance. Importantly, this correlation was largely driven by first-time vaccinees; prior influenza vaccination negatively correlated with vaccine immunogenicity. In support of these observations, dietary fibre consumption significantly enhanced humoral influenza vaccine responses in mice, where the effect was mechanistically linked to short-chain fatty acids, the bacterial fermentation product of dietary fibre. Overall, these findings may bear significant importance for emerging infectious agents, such as COVID-19, and associated de novo vaccinations.
Differences in the Structural Components Influence the Pumping Capacity of Marine Sponges
Authors: Dahihande Azraj S. , Thakur Narsinh L.
Published: November 2021

Marine sponges are important sessile, benthic filter feeders with a body plan designed to pump water efficiently. The sponge body plan generally consists of mineral spicules, gelatinous mesohyl, and the pores and canals of the aquiferous system. These structural components have stark differences in compressibility, mass, and volume; therefore, their proportion and distribution are likely to affect sponge morphology, anatomy, contraction, and finally the pumping capacity. We examined seven demosponge species (from high spicule skeleton contents to no spicules) commonly found along the central west coast of India for structural components, such as total inorganic contents (spicule skeleton and foreign inclusions), body density, porosity, and mesohyl TEM for the high microbial abundance/low microbial abundance status. Additionally, we estimated the sponge pumping rate by measuring the excurrent velocity, the abundance of individual pumping units and cells, i.e., choanocyte chambers and choanocytes, and also carried out a morphometric analysis of aquiferous structures. The excurrent velocity and the oscular flow rates showed a positive relationship with the oscular crosssectional area for all the study species. The inorganic spicule contents by their weight as well as volume formed a major component of tissue density and higher proportions of spicules were associated with reduced aquiferous structures and lower pumping rate. The ash mass% and the ash free dry weight (AFDW %) in the sponge dry mass showed separate and distinct associations with aquiferous system variables. For example, the number of choanocytes per chamber showed a wide difference between the studied species ranging from 35.02 ± 2.44 (C. cf. cavernosa) to 120.35 ± 8.98 (I. fusca) and had a significant positive relationship with AFDW% and a negative relationship with ash mass%. This study indicates that the differences in the proportions of structural components are closely related to sponge gross morphology, anatomy, and probably body contractions, factors that influence the sponge pumping capacity.
Sustenance of Indian Moored Buoy Network During COVID-19 Pandemic – A Saga of Perseverance
Authors: Venkatesan R. , Joseph K. Jossia , Prasad C. Anoopa , Kalyani M. , Muthiah M. Arul , Ramasundaram S. , Murugesh P. , Thirumurugan K. , Sundar R. , Kesavakumar B. , Vengatesan G. , Ramesh K. , Martin M. V. , Navaneeth K. N. , Senthilkumar P. , Haldar Biswajit , Tandon Abhishek , Sridharan R. , Jesuraj S. Sundar , Muthukumar C. , Sundaravadivelu N. , Saravanan M.
Published: November 2021

The moored buoy network in the Indian Ocean revolutionized the observational programs with systematic time-series measurement of in situ data sets from remote marine locations. The real-time meteorological and oceanographic data sets significantly improved the weather forecast and warning services particularly during extreme events since its inception in 1997. The sustenance of the network requires persistent efforts to overcome the multitude of challenges such as vandalism, biofouling, rough weather, corrosion, ship time availability, and telemetry issues, among others. Besides these, the COVID-19 pandemic constrained the normal functioning of activities, mainly by delaying the maintenance of the network that resulted in losing a few expensive buoy system components and precious data sets. However, the improvements in the buoy system, in-house developed data acquisition system, and efforts in ensuring the quality of measurements together with “best practice methods” enabled 73% of the buoy network to be functional even when the cruises were reduced to 33% during the COVID-19 lockdown in 2020. The moored buoys equipped with an Indian buoy data acquisition system triggered high-frequency transmission during the Super cyclone Amphan in May 2020, which greatly helped the cyclone early warning services during the COVID-19 pandemic. The COVID-19 lockdown points toward the reliability and enhanced utility of moored buoy observations particularly when other modes of measurements are limited and necessitates more such platforms to better predict the weather systems. The present study analyzed the enhancement of the buoy program and improvisation of the buoy system that extended the life beyond the stipulated duration and enabled the high-frequency data transmission during cyclones amid the COVID-19 lockdown. The recommendations to better manage the remote platforms specifically in the event of a pandemic based on the operational experience of more than two decades were also presented.
Study of Heavy Metals and Microbial Communities in Contaminated Sediments Along an Urban Estuary
Authors: Yi Jun , Lo Linus Shing Him , Liu Hongbin , Qian Pei-Yuan , Cheng Jinping
Published: November 2021

Estuarine sediments are increasingly contaminated by heavy metals as a result of urbanization and human activities. Continuous multi-heavy metal accumulation in the ecosystem can provoke new effects on top of the complex environmental interactions already present in estuarine ecosystems. It is important to study their integrated influence on imperative microbial communities to reflect on the environmental and ecological risks they may impose. Inductively coupled plasma optical emission spectroscopy analysis for five metals Cd, Cr, Cu, Pb, and Zn showed that Cr and Cu concentrations in intertidal sediments of the urbanized Yangtze River estuary in China have consistently exceeded respective threshold effect concentration (TEC) levels. The geo-accumulation and potential ecological risk index results of the five metals showed that all sampling sites were weakly to moderately polluted, and at considerable to high ecological risk, respectively. Redundancy and correlation analyses showed that Zn followed by Cr in the ecosystem were explanatory of the shifts in recorded microbial community structures. However, the spatial variation in metal concentrations did not correspond to the selection of metal resistance genes (MRGs). Unlike many other dominant bacterial taxa, most of the sulfate-reducing bacteria (SRB) and associated sulfate respiration as the dominant microbially contributed ecological function were found to negatively correlate with Zn and total heavy metal pollution. Zn concentration was proposed to be a potent indicator for heavy metal pollution-associated microbial community compositional shifts under urbanized estuarine conditions. The associations between heavy metals and estuarine microbial communities in this study demonstrate the influence of heavy metals on microbial community structure and adaptations that is often overshadowed by environmental factors (i.e., salinity and nutrients).
Polyacrylamide-Sodium Alginate Hydrogel Releasing Oxygen and Vitamin C Promotes Bone Regeneration in Rat Skull Defects
Authors: Zhao Bin , He Jingya , Wang Feng , Xing Ruxiao , Sun Bin , Zhou Yanmin
Published: November 2021

Oxygen is essential for cell survival and tissue regeneration. Scaffolds releasing oxygen have been hypothesized as an ideal strategy for bone repair. However, excessive oxygen supply will disturb the redox balance, lead to oxidative stress, and affect bone regeneration. In this study, we synthesized a hydrogel from sodium alginate and loaded it calcium peroxide nanoparticles as an oxygen generating material and vitamin C as a pH regulator and antioxidant. The composite hydrogel, with a pH value close to physiological humoral fluid, could release oxygen to alleviate hypoxia in the bone defect and reduce the side effects of excessive hydrogen peroxide. In in vitro experiments, the composite hydrogel promoted the osteogenic differentiation and ALP and mineralization ability of rat bone marrow mesenchymal stem cells in a hypoxic environment (2% O2). In animal experiments, the composite hydrogel was applied in rat skull defect models. It promoted the healing of bone defects. These results suggest that sodium alginate hydrogel releasing oxygen and vitamin C is suitable for cell survival and tissue regeneration in a hypoxic environment and has good application prospects in bone defect repair.
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 < 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.
Diversity, Chemical Constituents, and Biological Activities of Endophytic Fungi Isolated From Ligusticum chuanxiong Hort
Authors: Tang Zizhong , Qin Yihan , Chen Wenhui , Zhao Zhiqiao , Lin Wenjie , Xiao Yirong , Chen Hong , Liu Yuntao , Chen Hui , Bu Tongliang , Li Qingfeng , Cai Yi , Yao Huipeng , Wan Yujun
Published: November 2021

The objective of this study was to evaluate the diversity of endophytic fungi of different parts of Ligusticum chuanxiong Hort (CX) and further characterize their biological activities and identify chemical compounds produced by these endophytic fungi. A total of 21 endophytic fungi were isolated and identified from CX. Penicillium oxalicum, Simplicillium sp., and Colletotrichum sp. were identified as promising strains by the color reaction. Comparing different organic extracts of the three strains, it was observed that the ethyl acetate extract of Penicillium oxalicum and Simplicillium sp. and the n-butanol extract of Colletotrichum sp. showed significant antioxidant and antibacterial activities. The ethyl acetate extracts of Penicillium oxalicum had outstanding antioxidant and antibacterial effects, and its radical scavenging rates for ABTS and DPPH were 98.43 ± 0.006% and 90.11 ± 0.032%, respectively. At the same time, their IC50 values were only 0.18 ± 0.02 mg/mL and 0.04 ± 0.003 mg/mL. The ethyl acetate extract of Penicillium oxalicum showed MIC value of only 0.5 mg/mL against Escherichia coli and Staphylococcus aureus. By liquid chromatography-mass spectrometry (LC-MS), we found that Penicillium oxalicum could produce many high-value polyphenols, such as hesperidin (36.06 μmol/g), ferulic acid (1.17 μmol/g), and alternariol (12.64 μmol/g), which can be a potential resource for the pharmaceutical industry. In conclusion, these results increase the diversity of CX endophytic fungi and the antioxidant and antibacterial activities of their secondary metabolites.
Distinct Patterns of P1 and C2 VEP Potentiation and Attenuation in Visual Snow: A Case Report
Authors: Harris Alison M.
Published: November 2021

Visual snow syndrome, characterized by persistent flickering dots throughout the visual field, has been hypothesized to arise from abnormal neuronal responsiveness in visual processing regions. Previous research has reported a lack of typical VEP habituation to repeated stimulus presentation in patients with visual snow. Yet these studies generally used pattern-reversal paradigms, which are suboptimal for measuring cortical responses to the onset of foveal stimulation. Instead, these responses are better indexed by the C2, a pattern-onset VEP peaking 100–120 ms after stimulus onset. In this case study, we analyzed the C2 and its adaptation profile in data previously collected from a single patient with visual snow using a “double-pulse” presentation paradigm. In controls, shorter intervals between stimulus pairs were associated with greater attenuation of the C2 VEP, with recovery from adaptation at longer stimulus onset asynchronies (SOAs). However, the visual snow patient showed the opposite pattern, with reduced C2 amplitude at longer SOAs despite distinct C2 peaks at the shortest SOAs. These results stand in contrast not only to the pattern of C2 VEP attenuation in controls, but also to a lack of adaptation previously reported for the pattern-onset P1 VEP in this patient. Exploratory source localization using equivalent current dipole fitting further suggested that P1 and C2 VEPs in the visual snow patient arose from distinct sources in extrastriate visual cortex. While preliminary, these results support differential patterns of VEP attenuation and potentiation within the same individual, potentially pointing toward multiple mechanisms of abnormal neuronal responsiveness in visual snow syndrome.
Ultrasound-Guided Thermal Ablation of Thyroid Nodules: Technicalities Progress and Clinical Applications, Especially in Malignant Thyroid Nodules
Authors: Agyekum Enock Adjei , Fu Jian-hua , Xu Fei-Ju , Ren Yong-Zhen , Akortia Debora , Chen Qing , Qian Xiao-Qin , Wang Yuguo , Wang Xian
Published: November 2021

Thyroid nodules are commonly encountered in health care practice. They are usually benign in nature, with few cases being malignant, and their detection has increased in the adult population with the help of ultrasonography. Thyroidectomy or surgery is the first-line treatment and traditional method for thyroid nodules; however, thyroidectomy leaves permanent scars and requires long-term use of levothyroxine after surgery, which makes patients more reticent to accept this treatment. Thermal ablation is a minimally-invasive technique that have been employed in the treatment of benign and malignant thyroid nodules nodules, and have been shown to be effective and safe. Several studies, including long-term, retrospective, and prospective studies, have investigated the use of ablation to treat benign thyroid nodules and malignant thyroid nodules, including papillary thyroid carcinoma. Here, we review the recent progress in thermal ablation techniques for treating benign and malignant nodules, including their technicalities, clinical applications, pitfalls and limitations, and factors that could affect treatment outcomes. Special in-depth elaboration on the recent progress of the application of thermal ablation therapy in malignant thyroid nodules.
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

Purpose

Tumor 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).

Methods

A 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.

Results

Four 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 < 0.001, p < 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.

Conclusion

The 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

Purpose

In 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?

Methods

We 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.

Results

The 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.

Conclusion

These 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

Background

Prostate 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.

Methods

We 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.

Results

TAC 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).

Conclusions

Although 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.
Foliar Application of Boron Nanoencapsulated in Almond Trees Allows B Movement Within Tree and Implements Water Uptake and Transport Involving Aquaporins
Authors: Rios Juan J. , Lopez-Zaplana Alvaro , Bárzana Gloria , Martinez-Alonso Alberto , Carvajal Micaela
Published: November 2021

Nanotechnology brings to agriculture new forms of fertilizer applications, which could be used to reduce environmental contamination and increase efficiency. In this study, foliar fertilization with nanoencapsulated boron (B) was studied in comparison to an ionic B (non-encapsulated) application in young B-deficient almond trees grown under a controlled environment. B movement within the plant in relation to the leaf gas exchange, water relations parameters, and root hydraulic conductance was measured. Also, the expression of aquaporins (AQPs) [plasma membrane intrinsic protein (PIP) and tonoplast intrinsic protein (TIP)] was studied in relation to water uptake and transport parameters to establish the effectiveness of the different B treatments. The obtained results were associated with a high concentration of observed B with nanoencapsulated B, provided by the higher permeability of carrier nanovesicles, which allowed B to reach the cell wall more efficiently. The increases in water uptake and transport obtained in these plants could be related to the role that this element played in the cell wall and the relationship that it could have in the regulation of the expression of AQPs and their involvement in water relations. Also, an increase in the expression of PIPs (mainly PIP2.2) to the applied nanoencapsulated B could be related to the need for B and water transport, and fine regulation of TIP1.1 in relation to B concentration in tissues provides an important feature in the remobilization of B within the cell.
Ectopic Expression of VvSUC27 Induces Stenospermocarpy and Sugar Accumulation in Tomato Fruits
Authors: Cai Yumeng , Yin Ling , Tu Wenrui , Deng Zhefang , Yan Jing , Dong Wenjie , Gao Han , Xu Jinxu , Zhang Nan , Wang Jie , Zhu Lei , Meng Qingyong , Zhang Yali
Published: November 2021

Seedless fruits are favorable in the market because of their ease of manipulation. Sucrose transporters (SUTs or SUCs) are essential for carbohydrate metabolism in plants. Whether SUTs participate directly in causing stenospermocarpy, thereby increasing fruit quality, remains unclear. Three SUTs, namely, VvSUC11, VvSUC12, and VvSUC27 from Vitis vinifera, were characterized and ectopic expression in tomatoes. VvSUC11- and VvSUC12-overexpressing lines had similar flower and fruit phenotypes compared with those of the wild type. VvSUC27-overexpressing lines produced longer petals and pistils, an abnormal stigma, much less and shrunken pollen, and firmer seedless fruits. Moreover, produced fruits from all VvSUC-overexpressing lines had a higher soluble solid content and sugar concentration. Transcriptomic analysis revealed more genes associated with carbohydrate metabolism and sugar transport and showed downregulation of auxin- and ethylene-related signaling pathways during early fruit development in VvSUC27-overexpressing lines relative to that of the wild type. Our findings demonstrated that stenospermocarpy can be induced by overexpression of VvSUC27 through a consequential reduction in nutrient delivery to pollen at anthesis, with a subsequent downregulation of the genes involved in carbohydrate metabolism and hormone signaling. These commercially desirable results provide a new strategy for bioengineering stenospermocarpy in tomatoes and in other fruit plants.
Presence of Three-Dimensional Sound Field Facilitates Listeners’ Mood, Felt Emotion, and Respiration Rate When Listening to Music
Authors: Ooishi Yuuki , Kobayashi Maori , Kashino Makio , Ueno Kanako
Published: November 2021

Many studies have investigated the effects of music listening from the viewpoint of music features such as tempo or key by measuring psychological or psychophysiological responses. In addition, technologies for three-dimensional sound field (3D-SF) reproduction and binaural recording have been developed to induce a realistic sensation of sound. However, it is still unclear whether music listened to in the presence of 3D-SF is more impressive than in the absence of it. We hypothesized that the presence of a 3D-SF when listening to music facilitates listeners’ moods, emotions for music, and physiological activities such as respiration rate. Here, we examined this hypothesis by evaluating differences between a reproduction condition with headphones (HD condition) and one with a 3D-SF reproduction system (3D-SF condition). We used a 3D-SF reproduction system based on the boundary surface control principle (BoSC system) to reproduce a sound field of music in the 3D-SF condition. Music in the 3D-SF condition was binaurally recorded through a dummy head in the BoSC reproduction room and reproduced with headphones in the HD condition. Therefore, music in the HD condition was auditorily as rich in information as that in the 3D-SF condition, but the 3D-sound field surrounding listeners was absent. We measured the respiration rate and heart rate of participants listening to acousmonium and pipe organ music. The participants rated their felt moods before and after they listened to music, and after they listened, they also rated their felt emotion. We found that the increase in respiration rate, the degree of decrease in well-being, and unpleasantness for both pieces in the 3D-SF condition were greater than in the HD condition. These results suggest that the presence of 3D-SF enhances changes in mood, felt emotion for music, and respiration rate when listening to music.
Everyday Agency: Rethinking Refugee Women’s Agency in Specific Cultural Contexts
Authors: Kanal Maria , Rottmann Susan B.
Published: November 2021

This article proposes an interdisciplinary approach to refugee agency – the capacity to act within structural conditions – using the example of Syrian women rebuilding family and home in Turkey. Our broader objective is to prompt a re-thinking of refugee women’s everyday agency for scholars researching migration. The dominant manner of studying agency tends to be centered on refugees’ efforts to change their particular situations. Drawing on the latest theoretical propositions of cultural psychology (collective coping and the cultural coping model), we argue that agency can also be observed through examining how refugees rebuild their lives in the face of the many changes and challenges they have experienced. Guided by the cultural coping model, we describe stressors and coping strategies in context. With this approach, we can escape the trap of viewing refugee women in dichotomous ways, either as traumatized victims or as liberated from “traditional patriarchy.” A total of 33 semi-structured interviews were conducted in Turkey with Syrian, Arabic-speaking adult women. Interviews aimed to obtain comprehensive narratives on acculturation, daily stressors, coping strategies and everyday experiences of uprootedness. We used constructivist grounded theory (Charmaz, 2006) to identify significant themes (initial coding) and then code for more conceptual units of meaning (focused coding). The findings are structured around context specific themes: stressors and coping strategies. The study revealed three important types of stressors: family-related, role-related and place-related stressors. Each stressor can only be understood within the cultural context of inter-dependent agency, motherhood and neighborhood belonging, which are highly valued lived experiences of the refugee women. The study also identified three coping strategies: faith-based, home-making and identity building strategies. Our research shows that relying on Islamic understandings, creating the routines of a happy home and forging neighborly ties are important gender and culture specific manifestations of agency. The value of this research is that it provides migration scholars a useful model for designing research with female refugees. By identifying and writing about these specific and contextual forms of agency, researchers can provide better support to refugee women in their daily lives, while also challenging the image of passive “womenandchildren.”
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.