bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-reported oral health knowledge, Behavior and Attitude among students of a dental institution in a neo-capital region, Andhra Pradesh.
Authors: Jampani Yaswitha , Kandukuri Deepika , Simha B Vikram , Lodagala Asha , Kasarnenivi Namratha
Published: April 2021

Aim: To compare the oral health knowledge, attitude and behavior among pre-clinical and clinical undergraduate dental students.

Methodology: A questionnaire based cross-sectional study was conducted among pre-clinical and clinical undergraduate students at a teaching dental institution in Andhra Pradesh.A total of 357students were selected using non- probability purposive sampling technique. Modified English version of Hiroshima University Dental Behavior Inventory (HU-DBI) Questionnaire consisting of 31 closed ended questions has been implemented in this study after performing appropriate psychometric analysis.
Results:Knowledge, attitude and behavior differences between preclinical and clinical students were analyzed by Student’s t-testand statistically significant difference was obtained with p value of 0.004.Chi- square test was employed for dichotomous datai.e. to find the differences in the distribution of "yes" among students from the different academic year as well as between male and female students.Majority of females (86.3%) have responded that they don’t use tooth brush with hard bristles for cleaning their teeth which is high when compared to males (73.4%) and the difference is statistically significant (p=0.01). There is also a statistically significant difference with respect to smoking habits between males and females (p=0.003).

CONCLUSION: The outcome of this study shows clinical students having higher oral health knowledge, attitude and behavior scoresthan preclinical students and also the self-reported quality of overall oral health behavior was more pronounced in clinical students.Specific educational and awarenessprograms should be planned for the preclinical students.

Keywords: Dental students, Oral health knowledge, Oral health behavior,Oral health education.
Electrospun Polydioxanone Loaded With Chloroquine Modulates Template-Induced NET Release and Inflammatory Responses From Human Neutrophils
Authors: Fetz Allison E. , Wallace Shannon E. , Bowlin Gary L.
Published: April 2021

The implantation of a biomaterial quickly initiates a tissue repair program initially characterized by a neutrophil influx. During the acute inflammatory response, neutrophils release neutrophil extracellular traps (NETs) and secrete soluble signals to modulate the tissue environment. In this work, we evaluated chloroquine diphosphate, an antimalarial with immunomodulatory and antithrombotic effects, as an electrospun biomaterial additive to regulate neutrophil-mediated inflammation. Electrospinning of polydioxanone was optimized for rapid chloroquine elution within 1 h, and acute neutrophil-biomaterial interactions were evaluated in vitro with fresh human peripheral blood neutrophils at 3 and 6 h before quantifying the release of NETs and secretion of inflammatory and regenerative factors. Our results indicate that chloroquine suppresses NET release in a biomaterial surface area–dependent manner at the early time point, whereas it modulates signal secretion at both early and late time points. More specifically, chloroquine elution down-regulates interleukin 8 (IL-8) and matrix metalloproteinase nine secretion while up-regulating hepatocyte growth factor, vascular endothelial growth factor A, and IL-22 secretion, suggesting a potential shift toward a resolving neutrophil phenotype. Our novel repurposing of chloroquine as a biomaterial additive may therefore have synergistic, immunomodulatory effects that are advantageous for biomaterial-guided in situ tissue regeneration applications.
Ventilation System Design and the Coronavirus (COVID-19)
Authors: Afshari Alireza , Hultmark Göran , Nielsen Peter V. , Maccarini Alessandro
Published: April 2021

Most new office buildings in Nordic countries are equipped with balanced mechanical ventilation systems. The purpose of ventilation in office buildings is to provide thermal control by supplying cold or warm air for adequate indoor air quality. However, the role of ventilation in preventing virus transmission and maintaining a sufficient fresh air supply to obtain a low virus level through dilution is not currently well defined. Ventilation in office buildings is expected to contribute to preventing the spread of contaminants and provide comfort for occupants. The study reveals differences between risk areas for spreading airborne contaminants in office buildings in northern Europe, including Denmark, Norway and Sweden. The differences in the spread depends on different ventilation designs used in different countries.
A Power Customer Data Relational Algorithm Based on Magnanimity Fuzzy Address Matching
Authors: Jin Peng , Yang Jing , Wang Zongwei , Bu Xiaoyang , Wu Peng
Published: April 2021

According to the short text and unstructured characteristics of customer address, a data association fusion method for address has been proposed. In this method, the address was mapped to a digital fingerprint by improved Simhash technology, which effectively reduced the dimension of massive addresses and simplified the similarity-matching process of multi-source heterogeneous addresses. Furthermore, the weight setting of the eigenvector of the simhash algorithm was improved by introducing special weight gain. A two-level index mechanism was established by the characteristics of address division and data structure of digital fingerprints; the time-consuming digital fingerprint comparison was greatly reduced. The experimental results showed that calculation efficiency was greatly optimized; accuracy and coverage of the comparison were ensured. Through address matching of different databases, information fusion can be completed and the goal which power customers' demands is connected to power grid equipment is achieved.
EnRank: An Ensemble Method to Detect Pulmonary Hypertension Biomarkers Based on Feature Selection and Machine Learning Models
Authors: Liu Xiangju , Zhang Yu , Fu Chunli , Zhang Ruochi , Zhou Fengfeng
Published: April 2021

Pulmonary hypertension (PH) is a common disease that affects the normal functioning of the human pulmonary arteries. The peripheral blood mononuclear cells (PMBCs) served as an ideal source for a minimally invasive disease diagnosis. This study hypothesized that the transcriptional fluctuations in the PMBCs exposed to the PH arteries may stably reflect the disease. However, the dimension of a human transcriptome is much higher than the number of samples in all the existing datasets. So, an ensemble feature selection algorithm, EnRank, was proposed to integrate the ranking information of four popular feature selection algorithms, i.e., T-test (Ttest), Chi-squared test (Chi2), ridge regression (Ridge), and Least Absolute Shrinkage and Selection Operator (Lasso). Our results suggested that the EnRank-detected biomarkers provided useful information from these four feature selection algorithms and achieved very good prediction accuracy in predicting the PH patients. Many of the EnRank-detected biomarkers were also supported by the literature.
Case Report: First Two Identified Cases of Fabry Disease in Central Asia
Authors: Cainelli Francesca , Argandykov Dias , Kaldarbekov Dauren , Mukarov Murat , Tran Thi Phuong Liên , Germain Dominique P.
Published: April 2021

Background: Fabry disease (FD, OMIM #301500) is a rare, progressive, X-linked inherited, genetic disease due to the functional deficiency of lysosomal α-galactosidase (α-GAL) that leads to the accumulation of glycosphingolipids (mainly globotriaosylceramide or Gb3) and its derivative globotriaosylsphingosine or lyso-Gb3. Classic FD is a multisystem disorder which initially presents in childhood with neuropathic pain and dermatological, gastrointestinal, ocular, and cochleo-vestibular manifestations. Over time, end-organ damage such as renal failure, cardiac arrhythmia and early stroke may develop leading to reduced life expectancy in the absence of specific treatment.

Case presentation: We describe two Kazakh patients who presented in adulthood with a delayed diagnosis. We conducted also a family screening through cascade genotyping.

Conclusion: This is the first description of cases of Fabry disease in Central Asia. An extensive family pedigree enabled the identification of ten additional family members. Patients with rare genetic diseases often experience substantial delays in diagnosis due to their rarity and non-specific symptoms, which can negatively impact their management and delay treatment. FD may be difficult to diagnose because of the non-specificity of its early and later-onset symptoms and its X-linked inheritance. Raising awareness of clinicians is important for earlier diagnosis and optimal outcome of specific therapies.
Regulation of Inflammatory Response by Transmembrane Adaptor Protein LST1
Authors: Fabisik Matej , Tureckova Jolana , Pavliuchenko Nataliia , Kralova Jarmila , Balounova Jana , Vicikova Kristina , Skopcova Tereza , Spoutil Frantisek , Pokorna Jana , Angelisova Pavla , Malissen Bernard , Prochazka Jan , Sedlacek Radislav , Brdicka Tomas
Published: April 2021

LST1 is a small adaptor protein expressed in leukocytes of myeloid lineage. Due to the binding to protein tyrosine phosphatases SHP1 and SHP2 it was thought to have negative regulatory function in leukocyte signaling. It was also shown to be involved in cytoskeleton regulation and generation of tunneling nanotubes. LST1 gene is located in MHCIII locus close to many immunologically relevant genes. In addition, its expression increases under inflammatory conditions such as viral infection, rheumatoid arthritis and inflammatory bowel disease and its deficiency was shown to result in slightly increased sensitivity to influenza infection in mice. However, little else is known about its role in the immune system homeostasis and immune response. Here we show that similar to humans, LST1 is expressed in mice in the cells of the myeloid lineage. In vivo, its deficiency results in alterations in multiple leukocyte subset abundance in steady state and under inflammatory conditions. Moreover, LST1-deficient mice show significant level of resistance to dextran sodium sulphate (DSS) induced acute colitis, a model of inflammatory bowel disease. These data demonstrate that LST1 regulates leukocyte abundance in lymphoid organs and inflammatory response in the gut.
Protein-Based Immunome Wide Association Studies (PIWAS) for the Discovery of Significant Disease-Associated Antigens
Authors: Haynes Winston A. , Kamath Kathy , Waitz Rebecca , Daugherty Patrick S. , Shon John C.
Published: April 2021

Identification of the antigens associated with antibodies is vital to understanding immune responses in the context of infection, autoimmunity, and cancer. Discovering antigens at a proteome scale could enable broader identification of antigens that are responsible for generating an immune response or driving a disease state. Although targeted tests for known antigens can be straightforward, discovering antigens at a proteome scale using protein and peptide arrays is time consuming and expensive. We leverage Serum Epitope Repertoire Analysis (SERA), an assay based on a random bacterial display peptide library coupled with next generation sequencing (NGS), to power the development of Protein-based Immunome Wide Association Study (PIWAS). PIWAS uses proteome-based signals to discover candidate antibody-antigen epitopes that are significantly elevated in a subset of cases compared to controls. After demonstrating statistical power relative to the magnitude and prevalence of effect in synthetic data, we apply PIWAS to systemic lupus erythematosus (SLE, n=31) and observe known autoantigens, Smith and Ribosomal protein P, within the 22 highest scoring candidate protein antigens across the entire human proteome. We validate the magnitude and location of the SLE specific signal against the Smith family of proteins using a cohort of patients who are positive by predicate anti-Sm tests. To test the generalizability of the method in an additional autoimmune disease, we identified and validated autoantigenic signals to SSB, CENPA, and keratin proteins in a cohort of individuals with Sjogren’s syndrome (n=91). Collectively, these results suggest that PIWAS provides a powerful new tool to discover disease-associated serological antigens within any known proteome.
Mechanisms Used by Probiotics to Confer Pathogen Resistance to Teleost Fish
Authors: Simón Rocío , Docando Félix , Nuñez-Ortiz Noelia , Tafalla Carolina , Díaz-Rosales Patricia
Published: April 2021

Probiotics have been defined as live microorganisms that when administered in adequate amounts confer health benefits to the host. The use of probiotics in aquaculture is an attractive bio-friendly method to decrease the impact of infectious diseases, but is still not an extended practice. Although many studies have investigated the systemic and mucosal immunological effects of probiotics, not all of them have established whether they were actually capable of increasing resistance to different types of pathogens, being this the outmost desired goal. In this sense, in the current paper, we have summarized those experiments in which probiotics were shown to provide increased resistance against bacterial, viral or parasitic pathogens. Additionally, we have reviewed what is known for fish probiotics regarding the mechanisms through which they exert positive effects on pathogen resistance, including direct actions on the pathogen, as well as positive effects on the host.
TCRβ Sequencing Reveals Spatial and Temporal Evolution of Clonal CD4 T Cell Responses in a Breach of Tolerance Model of Inflammatory Arthritis
Authors: Al Khabouri Shaima , Benson Robert A. , Prendergast Catriona T. , Gray Joshua I. , Otto Thomas D. , Brewer James M. , Garside Paul
Published: April 2021

Effective tolerogenic intervention in Rheumatoid Arthritis (RA) will rely upon understanding the evolution of articular antigen specific CD4 T cell responses. TCR clonality of endogenous CD4 T cell infiltrates in early inflammatory arthritis was assessed to monitor evolution of the TCR repertoire in the inflamed joint and associated lymph node (LN). Mouse models of antigen-induced breach of self-tolerance and chronic polyarthritis were used to recapitulate early and late phases of RA. The infiltrating endogenous, antigen experienced CD4 T cells in inflamed joints and LNs were analysed using flow cytometry and TCRβ sequencing. TCR repertoires from inflamed late phase LNs displayed increased clonality and diversity compared to early phase LNs, while inflamed joints remained similar with time. Repertoires from late phase LNs accumulated clones with a diverse range of TRBV genes, while inflamed joints at both phases contained clones expressing similar TRBV genes. Repertoires from LNs and joints at the late phase displayed reduced CDR3β sequence overlap compared to the early disease phase, however the most abundant clones in LNs accumulate in the joint at the later phase. The results indicate CD4 T cell repertoire clonality and diversity broadens with progression of inflammatory arthritis and is first reflected in LNs before mirroring in the joint. These observations imply that antigen specific tolerogenic therapies could be more effective if targeted at earlier phases of disease when CD4 T cell clonality is least diverse.
Hidden in Plain View: Discovery of Chimeric Diabetogenic CD4 T Cell Neo-Epitopes
Authors: Reed Brendan K. , Kappler John W.
Published: April 2021

The T cell antigens driving autoimmune Type 1 Diabetes (T1D) have been pursued for more than three decades. When diabetogenic CD4 T cell clones and their relevant MHCII antigen presenting alleles were first identified in rodents and humans, the path to discovering the peptide epitopes within pancreatic beta cell proteins seemed straightforward. However, as experimental results accumulated, definitive data were often absent or controversial. Work within the last decade has helped to clear up some of the controversy by demonstrating that a number of the important MHCII presented epitopes are not encoded in the natural beta cell proteins, but in fact are fusions between peptide fragments derived from the same or different proteins. Recently, the mechanism for generating these MHCII diabetogenic chimeric epitopes has been attributed to a form of reverse proteolysis, called transpeptidation, a process that has been well-documented in the production of MHCI presented epitopes. In this mini-review we summarize these data and their implications for T1D and other autoimmune responses.
Neutrophils Modulate Fibrogenesis in Chronic Pulmonary Diseases
Authors: Ding Lili , Yang Juan , Zhang Chunmei , Zhang Xiuna , Gao Pujun
Published: April 2021

Chronic inflammatory pulmonary diseases are characterized by recurrent and persistent inflammation of the airways, commonly associated with poor clinical outcomes. Although their etiologies vary tremendously, airway neutrophilia is a common feature of these diseases. Neutrophils, as vital regulators linking innate and adaptive immune systems, are a double-edged sword in the immune response of the lung involving mechanisms such as phagocytosis, degranulation, neutrophil extracellular trap formation, exosome secretion, release of cytokines and chemokines, and autophagy. Although neutrophils serve as strong defenders against extracellular pathogens, neutrophils and their components can trigger various cascades leading to inflammation and fibrogenesis. Here, we review current studies to elucidate the versatile roles of neutrophils in chronic pulmonary inflammatory diseases and describe the common pathogenesis of these diseases. This may provide new insights into therapeutic strategies for chronic lung diseases.
Large Acid-Evoked Currents, Mediated by ASIC1a, Accompany Differentiation in Human Dopaminergic Neurons
Authors: Neuhof Andreas , Tian Yuemin , Reska Anna , Falkenburger Björn H. , Gründer Stefan
Published: April 2021

Acid-sensing ion channels (ASICs) are proton-gated Na+channels. They contribute to synaptic transmission, neuronal differentiation and neurodegeneration. ASICs have been mainly characterized in neurons from mice or rats and our knowledge of their properties in human neurons is scarce. Here, we functionally characterized ASICs in differentiating LUHMES cells, a human mesencephalic cell line with characteristics of dopaminergic neurons. We find that LUHMES cells express functional ASICs, predominantly homomeric ASIC1a. Expression starts early during differentiation with a striking surge in current amplitude at days 4–6 of differentiation, a time point where—based on published data—LUHMES cells start expressing synaptic markers. Peak ASIC expression therefore coincides with a critical period of LUHMES cell differentiation. It was associated with increased excitability, but not paralleled by an increase in ASIC1 mRNA or protein. In differentiating as well as in terminally differentiated LUHMES cells, ASIC activation by slight acidification elicited large currents, action potentials and a rise in cytosolic Ca2+. Applying the ASIC pore blocker diminazene during differentiation reduced the length of neurites, consistent with the hypothesis that ASICs play a critical role in LUHMES cell differentiation. In summary, our study establishes LUHMES cells as a valuable model to study the role of ASICs for neuronal differentiation and potentially also cell death in a human cell line.
Key Characteristics of Nitrous Oxide-Induced Neurological Disorders and Differences Between Populations
Authors: Zhang Juanjuan , Xie Dandan , Zou Yanfeng , Yu Xuen , Ji Yang , Wang Chengyou , Lv Xinyi , Zhou Nong , Jiang Xiao , Wang Kai , Tian Yanghua
Published: April 2021

Background: Nitrous oxide (N2O), commonly known as laughing gas, is inhaled recreationally because it produces the feelings of euphoria and freedom from pain. The risk of neurological dysfunction secondary to N2O abuse and its clinical diagnosis are, however, not yet sufficiently recognized, especially in China. Here, we have summarized the key clinical characteristics of N2O-induced neurological disorders.

Materials and Methods: We recruited 20 patients with N2O-induced neurological disorders and analyzed their clinical features, laboratory data, magnetic resonance imaging and electromyography. We also carried out a literature review and compared 99 previously reported patients with our case series to confirm our results. Subgroup analysis was performed to explore the difference in demographical and clinical characteristics of N2O abuse between Asian and non-Asian patients.

Results: The most common initial symptoms of N2O-induced neurological disorders were weakness and/or paresthesia. Most patients presented with myelopathy and/or peripheral neuropathy. The most commonly involved segment of the spinal cord was the cervical spinal cord, extending over 4–6 vertebral levels, but more than half of the patients with myelopathy had no sensory change at the corresponding spinal level. Homocysteine was found to be the most sensitive and practical indicator for diagnosis. Subgroup analysis showed that the Asian patients (median: 22.0 years old, Q1–Q3:19.0–26.0 years old) with N2O abuse were younger than non-Asian patients [26.0 (22.3–31.0) years old, P = 2.8 × 10−4]. The incidence of myelopathy combined with peripheral neuropathy was significantly higher in Asian patients than in non-Asian patients, who had myelopathy or peripheral neuropathy (P = 2 × 10−5).

Conclusions: Key clinical characteristics of N2O abuse are longitudinally extensive cervical myelopathy and peripheral neuropathy. Recognition of these traits in young people in the age group of 20–30 years will provide important guidance for accurate diagnosis of neurological disease associated with N2O abuse. The clinical manifestations differ in Asian patients and non-Asian patients.
Initial Experience of Intentional Internal High-Dose Policy Volumetric Modulated Arc Therapy of Neck Lymph Node Metastases ≥ 2 cm in Patients With Head and Neck Squamous Cell Carcinoma
Authors: Kashihara Tairo , Nakamura Satoshi , Murakami Naoya , Ito Kimiteru , Matsumoto Yoshifumi , Kobayashi Kenya , Omura Go , Mori Taisuke , Honma Yoshitaka , Kubo Yuko , Okamoto Hiroyuki , Takahashi Kana , Inaba Koji , Okuma Kae , Igaki Hiroshi , Nakayama Yuko , Kato Ken , Matsumoto Fumihiko , Yoshimoto Seiichi , Itami Jun
Published: April 2021

Background and Purpose

Most locoregional recurrences after definitive radiotherapy for head and neck squamous cell carcinoma (HNSCC) develop “in-field.” Dose escalation while sparing organs at risk can be a good solution for improving local control without increasing adverse effects. This study investigated the safety and effectiveness of volumetric modulated arc therapy (VMAT) using intentionally internal high-dose policy (IIHDP) to treat neck lymph node metastases (NLNM) ≥ 2 cm in HNSCC patients.

Materials and Methods

We analyzed 71 NLNM from 51 HNSCC patients who had received definitive radiotherapy to treat NLNM ≥ 2 cm using the VMAT technique in our institution between February 2017 and August 2019. Thirty-seven NLNM from 25 patients were treated using IIHDP VMAT (group A), and 34 NLNM from 27 patients were treated with homogeneous-dose distribution policy (HDDP) VMAT (group B). One patient with three NLNM had one lymph node assigned to group A and the other two to group B. Adverse events and local recurrence-free survival (LRFS) was compared between the two groups.

Results

In the median follow-up period of 527 days, there were no significant differences between the groups in terms of dermatitis or mucositis ≥ grade 2/3, but LRFS was significantly longer in group A (p = 0.007). In the Cox regression analysis after adjustment for the propensity score, group A also showed an apparently superior LFRS.

Conclusion

Our initial experience of IIHDP VMAT suggested that IIHDP VMAT to treat HNSCC neck lymph node metastases measuring ≥ 2 cm was feasible and possibly led to better local control than HDDP VMAT.
The G4 Resolvase DHX36 Possesses a Prognosis Significance and Exerts Tumour Suppressing Function Through Multiple Causal Regulations in Non-Small Cell Lung Cancer
Authors: Cui Yuxin , Li Zhilei , Cao Junxia , Lane Jane , Birkin Emily , Dong Xuefei , Zhang Lijian , Jiang Wen G.
Published: April 2021

Lung cancer is one of the most prevalent cancers in both men and women worldwide. The nucleic acid G4 structures have been implicated in the transcriptional programmes of cancer-related genes in some cancers such as lung cancer. However, the role of the dominant G4 resolvase DHX36 in the progression of lung cancer remains unknown. In this study, by bioinformatic analysis of public datasets (TCGA and GEO), we find DHX36 is an independent prognosis indicator in non-small-cell lung carcinoma (NSCLC) with subtype dependence. The stable lentiviral knockdown of the DHX36 results in accelerated migration and aggregation of the S-phase subpopulation in lung cancer cells. The reduction of DHX36 level de-sensitises the proliferation response of lung cancer cells to chemotherapeutic drugs such as paclitaxel with cell dependence. The knockdown of this helicase leads to promoted tumour growth, demonstrated by a 3D fluorescence spheroid lung cancer model, and the stimulation of cell colony formation as shown by single-cell cultivation. High throughput proteomic array indicates that DHX36 functions in lung cancer cells through regulating multiple signalling pathways including activation of protein activity, protein autophosphorylation, Fc-receptor signalling pathway, response to peptide hormone and stress-activated protein kinase signalling cascade. A causal transcriptomic analysis suggests that DHX36 is significantly associated with mRNA surveillance, RNA degradation, DNA replication and Myc targets. Therefore, we unveil that DHX36 presents clinical significance and plays a role in tumour suppression in lung cancer, and propose a potentially new concept for an anti-cancer therapy based on helicase-specific targeting.
Genomic Analysis of Glioblastoma Multiforme Reveals a Key Transcription Factor Signature Relevant to Prognosis and the Immune Processes
Authors: Li Zhen-Hang , Guan Yan-Lei , Zhang Guo-Bin
Published: April 2021

Introduction

Glioblastoma multiforme (GBM) develops through the accumulation of both genetic and expression alterations. Although many gene signatures have been developed as prognostic and predictive biomarkers, their robustness and functional aspects are less well characterized. The expression of most genes is regulated by transcription factors (TFs); therefore, we aimed to investigate a TF signature relevant to GBM prognosis.

Methods

We used bioinformatic methods and data from public databases to establish four clusters of key TF genes, among which cluster 1, comprising 24 TFs, showed significant prognostic value. Further in silico functional analyses were applied to investigate the utility of the TF signature.

Results

Different mutation and copy number variation patterns were observed between different risk score groups (based on the TF signature). In silico analyses suggested that the cases with relative high risk scores were involved in immune and inflammatory processes or pathways.

Conclusion

The TF signature has significant prognostic value in different cohorts or subgroups of patients with GBM and could lead to the development immunotherapy for GBM.
Extracorporeal Membrane Oxygenation in Children With Cancer or Hematopoietic Cell Transplantation: Single-Center Experience in 20 Consecutive Patients
Authors: Potratz Jenny C. , Guddorf Sarah , Ahlmann Martina , Tekaat Maria , Rossig Claudia , Omran Heymut , Masjosthusmann Katja , Groll Andreas H.
Published: April 2021

Extracorporeal membrane oxygenation (ECMO) is a rescue therapy for severe respiratory and/or circulatory failure. Few data exist on the potential benefit of ECMO in immunocompromised pediatric patients with cancer and/or hematopoietic cell transplantation (HCT). Over a period of 12 years, eleven (1.9%) of 572 patients with new diagnosis of leukemia/lymphoma and nine (3.5%) of 257 patients post allogeneic HCT underwent ECMO at our center. Five (45%) and two (22%) patients, respectively, survived to hospital discharge with a median event-free survival of 4.2 years. Experiences and outcomes in this cohort may aid clinicians and families when considering ECMO for individual patients.
Cost-Effectiveness Analysis of Atezolizumab Versus Chemotherapy as First-Line Treatment for Metastatic Non-Small-Cell Lung Cancer With Different PD-L1 Expression Status
Authors: Liu Guoqiang , Kang Shuo , Wang Xinchen , Shang Fangjian
Published: April 2021

Background

Atezolizumab could significantly improve clinical outcomes and was associated with less toxicity compared with chemotherapy as the first-line treatment of PD-L1-selected patients with EGFR and ALK wild-type metastatic non-small-cell lung cancer (NSCLC). However, the economic outcomes remain unclear yet in China. This study aimed to investigate the cost-effectiveness of atezolizumab versus chemotherapy as first-line therapy for metastatic NSCLC with different PD-L1 expression status from the Chinese health sector perspective.

Methods

A decision-analytic model was conducted to evaluate the economic outcomes for the first-line treatment of EGFR and ALK wild-type metastatic NSCLC with atezolizumab and chemotherapy in high PD-L1 expression, high or intermediate PD-L1 expression and any PD-L1 expression populations, respectively. The efficacy and safety data were obtained from the IMpower110 trial. Cost and utility values were gathered from the local charges and published literatures. Incremental cost-effectiveness ratio (ICER) was estimated. A scenario analysis for a patient assistance program (PAP) was conducted. One-way and probabilistic sensitivity analyses were performed to explore the robustness of the model results.

Results

Atezolizumab yielded additional 0.91 QALYs, 0.57 QALYs, 0.42 QALYs in comparison with chemotherapy, and the ICERs were $123,778.60/QALY, $142,827.19/QALY, $168,902.66/QALY in the high PD-L1 expression, high or intermediate PD-L1 expression, and any PD-L1 expression populations, respectively. When PAP was available, the ICERs were $52,414.63/QALY, $52,329.73/QALY, $61,189.66/QALY in the three categories of PD-L1 expression status populations, respectively. The ICERs were exceed the willingness-to-pay (WTP) threshold of $30,828/QALY (three times of per capita gross domestic product of China in 2019) in China. One-way sensitivity analyses suggested that the cost of atezolizumab played a vital role in the model outcomes, and the probabilistic sensitivity analyses showed atezolizumab was unlikely to be cost-effective at the WTP threshold regardless of PD-L1 expression status and whether the PAP was available or not.

Conclusions

Atezolizumab as first-line treatment for PD-L1-selected metastatic NSCLC patients without EGFR mutations or ALK translocations is unlikely to be cost-effective compared with chemotherapy regardless of PD-L1 expression status in the Chinese context.
Case Report: Resection of Giant Endotracheal Hamartoma by Electrosurgical Snaring via Fiberoptic Bronchoscopy in a 9-Year-Old Boy
Authors: Wu Lei , Chen Wei , Li PengCheng , Li Shuxian , Chen Zhimin
Published: April 2021

Endotracheal hamartomas are rarely encountered in children. The symptoms of endotracheal hamartoma may include cough, dyspnea, hemoptysis, chest pain, purulent sputum, and fever. The non-specific symptoms often result in a delayed diagnosis. Among the various treatments of this rare disease, surgical resection seems to be the most widely used, while endoscopic treatment is rarely described. Herein, we describe the case of a 9-year-old boy with an endotracheal hamartoma that was successfully excised by electrosurgical snaring via fiberoptic bronchoscopy (FB). The resection of select benign endotracheal tumors in children can be conducted using electrocautery, which can be regarded as an alternative therapy to bronchotomy.
Risk Factors and Reasons for Treatment Abandonment for Patients With Esophageal Atresia: A Study From a Tertiary Care Hospital in Beijing, China
Authors: Yang Shen , Liao Junmin , Li Siqi , Hua Kaiyun , Wang Peize , Zhang Yanan , Zhao Yong , Gu Yichao , Li Shuangshuang , Huang Jinshi
Published: April 2021

Background: This study aims to identify the risk factors and reasons for treatment abandonment for patients with esophageal atresia (EA) in a tertiary care hospital in China.

Methods: A retrospective study was conducted on 360 patients with EA admitted to Beijing Children's Hospital between January 1, 2007 and June 1, 2020. Medical records for treatment abandonment and non-treatment abandonment patients were compared. Univariate and multivariate logistic regression analyses were conducted to identify potential risk factors for treatment abandonment.

Results: After the diagnosis of EA, parents of 107 patients refused surgical repair and discharged against medical advice, and 253 patients underwent surgical repair. Among these 253 patients, parents of 59 patients abandoned treatment after surgery; 52 patients were discharged in an unstable condition, and parents of seven patients abandoned resuscitation leading to death in the hospital. By comparing clinical characteristics between treatment abandonment before surgery (n = 107) and non-treatment abandonment (n = 253) groups, we found that mother's parity >1, unplanned admission to intensive care unit before surgery, associated anomalies, and Gross type A/B were significant independent risk factors for treatment abandonment before surgery. Furthermore, birth weight <2,545 g, being discharged from neonatal center/intensive care unit and other departments, unplanned admission to intensive care unit after surgery, operative time >133 min, admission before 2016, pneumothorax, and anastomotic leakage were significant independent risk factors for treatment abandonment after surgery. The reasons for treatment abandonment included financial difficulties, multiple malformations with poor prognosis, belief of incurability and concerns about the prognosis of the diseases, postoperative complications, and extensive length of intensive care unit stay.

Conclusions: Treatment abandonment of children with EA/TEF is still a common and serious problem in China. This study showed that EA/TEF patients in critical conditions, with associated anomalies, Gross type A/B, and who had occurrence of complications had high-risk for treatment abandonment.
State of the Art in Parent-Delivered Pain-Relieving Interventions in Neonatal Care: A Scoping Review
Authors: Ullsten Alexandra , Andreasson Matilda , Eriksson Mats
Published: April 2021

Introduction:Parents' active involvement during painful procedures is considered a critical first step in improving neonatal pain practices. Of the non-pharmacological approaches in use, the biopsychosocial perspective supports parent-delivered interventions, in which parents themselves mediate pain relief, consistent with modern family-integrated care. This scoping review synthesizes the available research to provide an overview of the state of the art in parent-delivered pain-relieving interventions.

Methods:A scoping review was performed to achieve a broad understanding of the current level of evidence and uptake of parent-driven pain- and stress-relieving interventions in neonatal care.

Results:There is a strong evidence for the efficacy of skin-to-skin contact and breastfeeding, preferably in combination. These parent-delivered interventions are safe, valid, and ready for prompt introduction in infants' pain care globally. Research into parents' motivations for, and experiences of, alleviating infant pain is scarce. More research on combined parent-delivered pain alleviation, including relationship-based interventions such as the parent's musical presence, is needed to advance infant pain care. Guidelines need to be updated to include infant pain management, parent-delivered interventions, and the synergistic effects of combining these interventions and to address parent involvement in low-income and low-tech settings.

Conclusions:A knowledge-to-practice gap currently remains in parent-delivered pain management for infants' procedure-related pain. This scoping review highlights the many advantages of involving parents in pain management for the benefit not only of the infant and parent but also of health care.
Effect of the Addition of Human Milk Fortifier to Breast Milk on the Early Recovery of Infants After Congenital Cardiac Surgery
Authors: Yu Xian-Rong , Xie Wen-Peng , Liu Jian-Feng , Wang Li-Wen , Cao Hua , Chen Qiang
Published: April 2021

Objective:This article studied the effect of breast milk supplemented with human milk fortifier (HMF) on the early recovery of infants after congenital cardiac surgery.

Methods:Infants undergoing congenital cardiac surgery were randomly divided into an intervention group (n= 27) and a control group (n= 27). Infants in the intervention group received HMF, and those in the control group were exclusively breastfed. The nutritional indicators at discharge, the postoperative recovery status, and nutritional-related complications were recorded.

Results:Compared with the control group at the time of discharge, the weight and albumin and prealbumin levels of the intervention group were significantly increased (P< 0.05). The length of hospital stay of the intervention group was significantly reduced compared with that of the control group (P< 0.05). Although the length of ICU stay for the intervention group was shorter than that of the control group, the difference was not significant (P> 0.05). No significant difference in the incidence of postoperative nutrition-related complications was noted between the two groups (P> 0.05).

Conclusion:Compared with breastfeeding alone, with HMF can improve postoperative weight gains, reduce the length of stay, and promote infants' early recovery after congenital cardiac surgery.
Annexin A2-Mediated Plasminogen Activation in Endothelial Cells Contributes to the Proangiogenic Effect of Adenosine A2A Receptors
Authors: Valls María D. , Soldado María , Arasa Jorge , Perez-Aso Miguel , Williams Adrienne J. , Cronstein Bruce N. , Noguera M. Antonia , Terencio M. Carmen , Montesinos M. Carmen
Published: April 2021

Adenosine A2A receptor mediates the promotion of wound healing and revascularization of injured tissue, in healthy and animals with impaired wound healing, through a mechanism depending upon tissue plasminogen activator (tPA), a component of the fibrinolytic system. In order to evaluate the contribution of plasmin generation in the proangiogenic effect of adenosine A2A receptor activation, we determined the expression and secretion of t-PA, urokinase plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1) and annexin A2 by human dermal microvascular endothelial cells stimulated by the selective agonist CGS-21680. The plasmin generation was assayed through an enzymatic assay and the proangiogenic effect was studied using an endothelial tube formation assay in Matrigel. Adenosine A2A receptor activation in endothelial cells diminished the release of PAI-1 and promoted the production of annexin A2, which acts as a cell membrane co-receptor for plasminogen and its activator tPA. Annexin A2 mediated the increased cell membrane-associated plasmin generation in adenosine A2A receptor agonist treated human dermal microvascular endothelial cells and is required for tube formation in an in vitro model of angiogenesis. These results suggest a novel mechanism by which adenosine A2A receptor activation promotes angiogenesis: increased endothelial expression of annexin A2, which, in turn, promotes fibrinolysis by binding tPA and plasminogen to the cell surface.
Pannexin-1 Contributes to the Apoptosis of Spinal Neurocytes in Spinal Cord Injury
Authors: Huang Yu , Lin Jin , Chen Xuanwei , Lin Jianhua
Published: April 2021

Currently, the role of Pannexin-1, a homomeric membrane hemichannel on the neuron cell membrane, in the development of spinal cord injury (SCI) is largely unknown. Herein, we assessed the contribution of Panx1 in the development of SCI. The SCI in vitro model was established using rat primary spinal neurocytes treated with hydrogen peroxide (H2O2). Effects of Panx1 overexpression or depletion in spinal neurocytes were analyzed by lentivirus-mediated transfection of Panx1 and interference sh-Panx1. Decreased cell viability was seen in SCI cells, which was further enhanced under Panx1 overexpression and mitigated by Panx1 deficiency. H2O2 induced an increase of intracellular Ca2+ signal and upregulated level of the proapoptotic protein Bax, and apoptosis pathway proteins including cleaved Caspase-3 and PARP1, which was enhanced by Panx1 overexpression or attenuated by Panx1 depletion. On the other hand, H2O2 treatment suppressed the level of antiapoptotic protein Bcl-2, which was further decreased by Panx1 overexpression or mitigated by Panx1 depletion. The results indicate that Panx1 was involved in the intracellular Ca2+ overload of SCI cells by accelerating extracellular Ca2+ influx, which promoted the apoptosis of spinal neurocytes through Ca2+ dependent pathways, thus aggravating the secondary injury of SCI.
Multiple Drivers of High Species Diversity and Endemism Among Alyssum Annuals in the Mediterranean: The Evolutionary Significance of the Aegean Hotspot
Authors: Cetlová Veronika , Zozomová-Lihová Judita , Melichárková Andrea , Mártonfiová Lenka , Španiel Stanislav
Published: April 2021

The Mediterranean Basin is a significant hotspot of species diversity and endemism, with various distribution patterns and speciation mechanisms observed in its flora. High species diversity in the Mediterranean is also manifested in the monophyletic lineage ofAlyssumannuals (Brassicaceae), but little is known about its origin. These species include both diploids and polyploids that grow mainly in open and disturbed sites across a wide elevational span and show contrasting distribution patterns, ranging from broadly distributed Eurasian species to narrow island endemics. Here, we investigated the evolution of European representatives of this lineage, and aimed to reconstruct their phylogeny, polyploid and genome size evolution using flow cytometric analyses, chloroplast and nuclear high- and low-copy DNA markers. The origin and early diversification of the studiedAlyssumlineage could be dated back to the Late Miocene/Pliocene and were likely promoted by the onset of the Mediterranean climate, whereas most of the extant species originated during the Pleistocene. The Aegean region represents a significant diversity center, as it hosts 12 out of 16 recognized European species and comprises several (sub)endemics placed in distinct phylogenetic clades. Because several species, including the closest relatives, occur here sympatrically without apparent niche differences, we can reject simple allopatric speciation via vicariance as well as ecological speciation for most cases. Instead, we suggest scenarios of more complex speciation processes that involved repeated range shifts in response to sea-level changes and recurrent land connections and disconnections since the Pliocene. In addition, multiple polyploidization events significantly contributed to species diversity across the entire distribution range. All seven polyploids, representing both widespread species and endemics to the western or eastern Mediterranean, were inferred to be allopolyploids. Finally, the current distribution patterns have likely been affected also by the human factor (farming and grazing). This study illustrates the complexity of evolutionary and speciation processes in the Mediterranean flora.
Semi-Quantitative Targeted Gas Chromatography-Mass Spectrometry Profiling Supports a Late Side-Chain Reductase Cycloartenol-to-Cholesterol Biosynthesis Pathway in Brown Algae
Authors: Girard Jean , Lanneau Goulven , Delage Ludovic , Leroux Cédric , Belcour Arnaud , Got Jeanne , Collén Jonas , Boyen Catherine , Siegel Anne , Dittami Simon M. , Leblanc Catherine , Markov Gabriel V.
Published: April 2021

Sterols are biologically important molecules that serve as membrane fluidity regulators and precursors of signaling molecules, either endogenous or involved in biotic interactions. There is currently no model of their biosynthesis pathways in brown algae. Here, we benefit from the availability of genome data and gas chromatography-mass spectrometry (GC-MS) sterol profiling using a database of internal standards to build such a model. We expand the set of identified sterols in 11 species of red, brown, and green macroalgae and integrate these new data with genomic data. Our analyses suggest that some metabolic reactions may be conserved despite the loss of canonical eukaryotic enzymes, like the sterol side-chain reductase (SSR). Our findings are consistent with the principle of metabolic pathway drift through enzymatic replacement and show that cholesterol synthesis from cycloartenol may be a widespread but variable pathway among chlorophyllian eukaryotes. Among the factors contributing to this variability, one could be the recruitment of cholesterol biosynthetic intermediates to make signaling molecules, such as the mozukulins. These compounds were found in some brown algae belonging to Ectocarpales, and we here provide a first mozukulin biosynthetic model. Our results demonstrate that integrative approaches can already be used to infer experimentally testable models, which will be useful to further investigate the biological roles of those newly identified algal pathways.
Youth Strike for Climate: Resistance of School Administrations, Conflicts Among Students, and Legitimacy of Autonomous Civil Disobedience—The Case of Québec
Authors: Dupuis-Déri Francis
Published: April 2021

This text presents the results of the first research conducted on “green” actions and strikes for climate in high schools across Québec, a Canadian province that witnessed in 2019 the larger street protests of the international youth movement. Based on 20 semistructured interviews with students from 12 high schools, letters from school principals addressed to parents, and research in the media, this text reaffirms that schools are a place of political conflicts and struggles not only between students and adults but also between students in opposite currents of the movement. It is also a reminder of the involvement of young people in autonomous direct action groups (Extinction Rebellion). The discussion then focuses on potential implications of the movement for future elections, the legitimacy of these collective actions in relation to the philosophical debate about civil disobedience (John Rawls, Ronald Dworkin, Manuel Cerveza-Marzal, and Alan Carter), and the hope for a renewal of the student movement in Québec in the face of a disaster of unprecedented scale.
Re-examining the New Product Paradox: How Innovation Ambidexterity Mediates the Market Orientation and New Product Development Performance Relationship
Authors: Zhao Anni , Bi Xinhua , Han Lei
Published: April 2021

More and more well-documented failure of established companies which could not respond to rapid market changes, such as Kodak and Nokia, demonstrate the importance of transferring marketing information into real firm performance. While marketing strategy and management literature has long advocated the direct impact of strong firm market orientation (MO) on new product development (NPD) performance, limited research has discussed the mediating mechanism of this MO-NPD performance relationship. Using the traditional source–position–performance (SPP) framework, this study focuses on the innovation ambidexterity perspective to investigate the mediating mechanism between MO and NPD performance. Then, this study proposed a conceptual framework and propositions to examine the MO - NPD performance relationship further. Theoretical and practical implications of the findings are also discussed.