bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-cell morphological characterization of CRH neurons throughout the whole mouse brain
Authors: Wang Yu , Hu Pu , Shan Qinghong , Huang Chuan , Huang Zhaohuan , Chen Peng , Li Anan , Gong Hui , Zhou Jiang-Ning
Published: March 2021

Background

Corticotropin-releasing hormone (CRH) is an important neuromodulator that is widely distributed in the brain and plays a key role in mediating stress responses and autonomic functions. While the distribution pattern of fluorescently labeled CRH-expressing neurons has been studied in different transgenic mouse lines, a full appreciation of the broad diversity of this population and local neural connectivity can only come from integration of single-cell morphological information as a defining feature. However, the morphologies of single CRH neurons and the local circuits formed by these neurons have not been acquired at brain-wide and dendritic-scale levels.

Results

We screened the EYFP-expressing CRH-IRES-Cre;Ai32 mouse line to reveal the morphologies of individual CRH neurons throughout the whole mouse brain by using a fluorescence micro-optical sectioning tomography (fMOST) system. Diverse dendritic morphologies and projection fibers of CRH neurons were found in various brain regions. Follow-up reconstructions showed that hypothalamic CRH neurons had the smallest somatic volumes and simplest dendritic branches and that CRH neurons in several brain regions shared a common bipolar morphology. Further investigations of local CRH neurons in the medial prefrontal cortex unveiled somatic depth-dependent morphologies of CRH neurons that exhibited three types of mutual connections: basal dendrites (upper layer) with apical dendrites (layer 3); dendritic-somatic connections (in layer 2/3); and dendritic-dendritic connections (in layer 4). Moreover, hypothalamic CRH neurons were classified into two types according to their somatic locations and characteristics of dendritic varicosities. Rostral-projecting CRH neurons in the anterior parvicellular area had fewer and smaller dendritic varicosities, whereas CRH neurons in the periventricular area had more and larger varicosities that were present within dendrites projecting to the third ventricle. Arborization-dependent dendritic spines of CRH neurons were detected, among which the most sophisticated types were found in the amygdala and the simplest types were found in the hypothalamus.

Conclusions

By using the CRH-IRES-Cre;Ai32 mouse line and fMOST imaging, we obtained region-specific morphological distributions of CRH neurons at the dendrite level in the whole mouse brain. Taken together, our findings provide comprehensive brain-wide morphological information of stress-related CRH neurons and may facilitate further studies of the CRH neuronal system.
Correction to: Safety of denervation following targeted lung denervation therapy for COPD: AIRFLOW-1 3-year outcomes
Authors: Pison Christophe , Shah Pallav L. , Slebos Dirk‑Jan , Ninane Vincent , Janssens Wim , Perez Thierry , Kessler Romain , Deslee Gaetan , Garner Justin L. , Hartman Jorine E. , Degano Bruno , Mayr Anna , Mayse Martin , Peterson Alexander D. , Valipour Arschang
Published: March 2021

An amendment to this paper has been published and can be accessed via the original article.
Understanding how communities respond to COVID-19: experiences from the Orthodox Jewish communities of Antwerp city
Authors: Vanhamel Jef , Meudec Marie , Van Landeghem Ella , Ronse Maya , Gryseels Charlotte , Reyniers Thijs , Rotsaert Anke , Ddungu Charles , Manirankunda Lazare , Katsuva Deogratias , Grietens Koen Peeters , Nöstlinger Christiana
Published: March 2021

Background

The importance of community involvement in the response against disease outbreaks has been well established. However, we lack insights into local communities’ experiences in coping with the current COVID-19 pandemic. This study explored both the impact of, and response to, COVID-19 within the Orthodox Jewish communities of Antwerp (Belgium) during the first lockdown period (March 2020 – May 2020).

Methods

We conducted an explorative qualitative study using a participatory approach. First, we performed a community mapping to identify relevant stakeholders. Through the active involvement of a community advisory board and based on qualitative interviews with key-informants and community members, we elicited lived experiences, attitudes, and perceptions towards COVID-19. Interviews were conducted both face-to-face and using online web conferencing technology. Data were analyzed inductively according to the principles of thematic analysis.

Results

Government-issued outbreak control measures presented context-specific challenges to the Orthodox Jewish communities in Antwerp. They related mainly to the remote organization of religious life, and practicing physical distancing in socially and culturally strongly connected communities. Existing community resources were rapidly mobilized to adapt to the outbreak and to self-organize response initiatives within communities. The active involvement of community and religious leaders in risk communication proved to be of great importance to facilitate the coverage and uptake of pandemic control measures while protecting essential community values and traditions. Creating bottom-up and community-adapted communication strategies, including addressing language barriers and involving Rabbis in the dissemination of prevention messages, fostered a feeling of trust in government’s response measures. However, unmet information and prevention needs were also identified, such as the need for inclusive communication by public authorities and the need to mitigate the negative effects of stigmatization.

Conclusion

The experiences of Orthodox Jewish communities in Antwerp demonstrate a valuable example of a feasible community-centered approach to health emergencies. Increasing the engagement of communities in local decision-making and governance structures remains a key strategy to respond to unmet information and prevention needs.
Severity of parkinsonism associated with environmental manganese exposure
Authors: Racette Brad A. , Nelson Gill , Dlamini Wendy W. , Prathibha Pradeep , Turner Jay R. , Ushe Mwiza , Checkoway Harvey , Sheppard Lianne , Nielsen Susan Searles
Published: March 2021

Background

Exposure to occupational manganese (Mn) is associated with neurotoxic brain injury, manifesting primarily as parkinsonism. The association between environmental Mn exposure and parkinsonism is unclear. To characterize the association between environmental Mn exposure and parkinsonism, we performed population-based sampling of residents older than 40 in Meyerton, South Africa (N = 621) in residential settlements adjacent to a large Mn smelter and in a comparable non-exposed settlement in Ethembalethu, South Africa (N = 95) in 2016–2020.

Methods

A movement disorders specialist examined all participants using the Unified Parkinson Disease Rating Scale motor subsection part 3 (UPDRS3). Participants also completed an accelerometry-based kinematic test and a grooved pegboard test. We compared performance on the UPDRS3, grooved pegboard, and the accelerometry-based kinematic test between the settlements using linear regression, adjusting for covariates. We also measured airborne PM2.5-Mn in the study settlements.

Results

Mean PM2.5-Mn concentration at a long-term fixed site in Meyerton was 203 ng/m3 in 2016–2017 – approximately double that measured at two other neighborhoods in Meyerton. The mean Mn concentration in Ethembalethu was ~ 20 times lower than that of the long-term Meyerton site. UPDRS3 scores were 6.6 (CI 5.2, 7.9) points higher in Meyerton than Ethembalethu residents. Mean angular velocity for finger-tapping on the accelerometry-based kinematic test was slower in Meyerton than Ethembalethu residents [dominant hand 74.9 (CI 48.7, 101.2) and non-dominant hand 82.6 (CI 55.2, 110.1) degrees/second slower]. Similarly, Meyerton residents took longer to complete the grooved pegboard, especially for the non-dominant hand (6.9, CI -2.6, 16.3 s longer).

Conclusions

Environmental airborne Mn exposures at levels substantially lower than current occupational exposure thresholds in the United States may be associated with clinical parkinsonism.
Correlation analysis of epicardial adipose tissue thickness, C-reactive protein, interleukin-6, visfatin, juxtaposed with another zinc finger protein 1, and type 2 diabetic macroangiopathy
Authors: Gong Yuan-Yuan , Peng Hai-Ying
Published: March 2021

Background

To investigate the correlation between the thickness of epicardial adipose tissue (EAT), C-reactive protein (CRP), interleukin (IL) -6, visfatin, juxtaposed with another zinc finger protein 1 (JAZF1) and type 2 diabetic mellitus (T2DM) macroangiopathy.

Methods

The study enrolled 82 patients with T2DM with macroangiopathy (the Complication Group), and 85 patients with T2DM (the Diabetes Group) who were admitted to Shandong Provincial Third Hospital from February 2018 to February 2020. In addition, 90 healthy people who underwent physical examination at the same hospital during the same period were enrolled (the Healthy Control Group). Age, gender, height, weight, waist circumference (WC), hip circumference (HC), diabetic course and therapeutic drugs, waist hip ratio (WHR), and body mass index (BMI) were recorded and calculated.

Results

The baseline characteristics of the three groups were comparable, and the diabetic course of the Complication Group and the Diabetes Group was not significantly different (P > 0.05). The WHR of the Complication Group was higher than that of the Diabetes Group and the Healthy Control Group, with statistical significance (P < 0.05). The FPG, 2hPG, HbA1C, CRP, IL-6, Visfatin, JAZF1, HOMA-IR, EAT thickness, and baPWV of the Complication Group were all higher than those of the Diabetes Group and the Healthy Control Group (P < 0.05, respectively). The JAZF1 and FIns of the Complication Group and Diabetes Group were lower than those of the Healthy Control Group, and JAZF1 of the Complication Group was lower than the Diabetes Group with statistical significance (P<0.05, respectively). Pearson correlation analysis showed that the EAT thickness was positively correlated with CRP, IL-6, visfatin, and JAZF1 (r = 0.387, 0.451, 0.283, 0.301, respectively, all P<0.001). Pearson correlation analysis showed that baPWV was positively correlated with EAT thickness, CRP, IL-6, visfatin, and JAZF1 (r = 0.293, 0.382, 0.473, 0.286, respectively, all P < 0.001). Multivariate stepwise regression analysis showed that FPG, 2hPG, HbA1C, CRP, IL-6, visfatin, JAZF1, and EAT thickness were independent risk factors that affected T2DM macroangiopathy.

Conclusions

Clinical monitoring and treatment of T2DM macroangiopathy can use CRP, IL-6, Visfatin, JAZF1, and EAT thickness as new targets to delay the progression of the disease. Further research on the relationship between the above factors and the pathogenesis of T2DM macroangiopathy may be helpful provide new treatment strategies.
Early oral feeding is safe and useful after rectosigmoid resection with anastomosis during cytoreductive surgery for primary ovarian cancer
Authors: Kato Kazuyoshi , Omatsu Kohei , Okamoto Sanshiro , Matoda Maki , Nomura Hidetaka , Tanigawa Terumi , Aoki Yoichi , Yunokawa Mayu , Kanao Hiroyuki
Published: March 2021

Background

The aim of this study was to investigate the safety and clinical usefulness of early oral feeding (EOF) after rectosigmoid resection with anastomosis for the treatment of primary ovarian cancer.

Methods

We performed a retrospective review of all consecutive patients who had undergone rectosigmoid resection with anastomosis for primary ovarian, tubal, or peritoneal cancer between April 2012 and March 2019 in a single institution. Patient-related, disease-related, and surgery-related data including the incidence of anastomotic leakage and postoperative hospital stay were collected. EOF was introduced as a postoperative oral feeding protocol in September 2016. Before the introduction of EOF, conventional oral feeding (COF) had been used.

Results

Two hundred and one patients who underwent rectosigmoid resection with anastomosis, comprised of 95 patients in the COF group and 106 patients in the EOF group, were included in this study. The median number of postoperative days until the start of diet intake was 5 (range 2–8) in the COF group and 2 (range 2–8) in the EOF group (P < 0.001). Postoperative morbidity was equivalent between the groups. The incidence of anastomotic leakage was similar (1%) in both groups. The median length of the postoperative hospital stay was reduced by 6 days for the EOF group: 17 (range 9–67) days for the COF group versus 11 (8–49) days for the EOF group (P < 0.001).

Conclusion

EOF provides a significant reduction in the length of the postoperative hospital stay without an increased complication risk after rectosigmoid resection with anastomosis as a part of cytoreductive surgery for primary ovarian cancer.
Hepatitis B virus X protein promotes vimentin expression via LIM and SH3 domain protein 1 to facilitate epithelial-mesenchymal transition and hepatocarcinogenesis
Authors: You Hongjuan , Yuan Dongchen , Bi Yanwei , Zhang Ning , Li Qi , Tu Tao , Wei Xiao , Lian Qi , Yu Tong , Kong Delong , Yang Xiaoying , Liu Xiangye , Liu Xiaomei , Kong Fanyun , Zheng Kuiyang , Tang Renxian
Published: March 2021

Background

Hepatitis B virus (HBV) X protein (HBX) has been reported to be responsible for the epithelial-mesenchymal transition (EMT) in HBV-related hepatocellular carcinoma (HCC). Vimentin is an EMT-related molecular marker. However, the importance of vimentin in the pathogenesis of HCC mediated by HBX has not been well determined.

Methods

The expression of vimentin induced by HBX, and the role of LIM and SH3 domain protein 1 (LASP1) in HBX-induced vimentin expression in hepatoma cells were examined by western blot and immunohistochemistry analysis. Both the signal pathways involved in the expression of vimentin, the interaction of HBX with vimentin and LASP1, and the stability of vimentin mediated by LASP1 in HBX-positive cells were assessed by western blot, Co-immunoprecipitation, and GST-pull down assay. The role of vimentin in EMT, proliferation, and migration of HCC cells mediated by HBX and LASP1 were explored with western blot, CCK-8 assay, plate clone formation assay, transwell assay, and wound healing assay.

Results

Vimentin expression was increased in both HBX-positive hepatoma cells and HBV-related HCC tissues, and the expression of vimentin was correlated with HBX in HBV-related HCC tissues. Functionally, vimentin was contributed to the EMT, proliferation, and migration of hepatoma cells mediated by HBX. The mechanistic analysis suggested that HBX was able to enhance the expression of vimentin through LASP1. On the one hand, PI3-K, ERK, and STAT3 signal pathways were involved in the upregulation of vimentin mediated by LASP1 in HBX-positive hepatoma cells. On the other hand, HBX could directly interact with vimentin and LASP1, and dependent on LASP1, HBX was capable of promoting the stability of vimentin via protecting it from ubiquitination mediated protein degradation. Besides these, vimentin was involved in the growth and migration of hepatoma cells mediated by LASP1 in HBX-positive hepatoma cells.

Conclusion

Taken together, these findings demonstrate that, dependent on LASP1, vimentin is crucial for HBX-mediated EMT and hepatocarcinogenesis, and may serve as a potential target for HBV-related HCC treatment.
The influence of BACE1 on macrophage recruitment and activity in the injured peripheral nerve
Authors: Fissel John A. , Farah Mohamed H.
Published: March 2021

Following peripheral nerve injury, multiple cell types, including axons, Schwann cells, and macrophages, coordinate to promote nerve regeneration. However, this capacity for repair is limited, particularly in older populations, and current treatments are insufficient. A critical component of the regeneration response is the network of cell-to-cell signaling in the injured nerve microenvironment. Sheddases are expressed in the peripheral nerve and play a role in the regulation if this cell-to-cell signaling through cleavage of transmembrane proteins, enabling the regulation of multiple pathways through cis- and trans-cellular regulatory mechanisms. Enhanced axonal regeneration has been observed in mice with deletion of the sheddase beta-secretase (BACE1), a transmembrane aspartyl protease that has been studied in the context of Alzheimer’s disease. BACE1 knockout (KO) mice display enhanced macrophage recruitment and activity following nerve injury, although it is unclear whether this plays a role in driving the enhanced axonal regeneration. Further, it is unknown by what mechanism(s) BACE1 increases macrophage recruitment and activity. BACE1 has many substrates, several of which are known to have immunomodulatory activity. This review will discuss current knowledge of the role of BACE1 and other sheddases in peripheral nerve regeneration and outline known immunomodulatory BACE1 substrates and what potential roles they could play in peripheral nerve regeneration. Currently, the literature suggests that BACE1 and substrates that are expressed by neurons and Schwann cells are likely to be more important for this process than those expressed by macrophages. More broadly, BACE1 may play a role as an effector of immunomodulation beyond the peripheral nerve.
Underlying mechanisms and drug intervention strategies for the tumour microenvironment
Authors: Li Haoze , Zhou Lihong , Zhou Jing , Li Qi , Ji Qing
Published: March 2021

Cancer occurs in a complex tissue environment, and its progression depends largely on the tumour microenvironment (TME). The TME has a highly complex and comprehensive system accompanied by dynamic changes and special biological characteristics, such as hypoxia, nutrient deficiency, inflammation, immunosuppression and cytokine production. In addition, a large number of cancer-associated biomolecules and signalling pathways are involved in the above bioprocesses. This paper reviews our understanding of the TME and describes its biological and molecular characterization in different stages of cancer development. Furthermore, we discuss in detail the intervention strategies for the critical points of the TME, including chemotherapy, targeted therapy, immunotherapy, natural products from traditional Chinese medicine, combined drug therapy, etc., providing a scientific basis for cancer therapy from the perspective of key molecular targets in the TME.
Extracorporeal cardiopulmonary resuscitation for severe chloroquine intoxication in a child – a case report
Authors: Ferry Thomas , Amiet Vivianne , Natterer Julia , Perez Marie-Hélène , Pfister Raymond , Colombier Sébastien , Longchamp David
Published: March 2021

Background

Chloroquine use has increased worldwide recently in the setting of experimental treatment for the novel coronavirus disease (Covid-19). Nevertheless, in case of chloroquine intoxication, it can be life threatening, with cardiac arrest, due to its cardiac toxicity.

Case presentation

This case study reports on a 14-years-old girl who presented in cardiac arrest after an uncommon suicide attempt by ingesting 3 g of chloroquine. After 66 min of cardio-pulmonary resuscitation (CPR), extracorporeal cardiopulmonary resuscitation (ECPR) was initiated, allowing cardiac function to recover.

Conclusions

Chloroquine intoxication is a rare but serious condition due to its cardiac toxicity. Use of ECPR in this case of transient toxicity allowed a favorable evolution with little neurological impairment.
A novel zinc complex with antibacterial and antioxidant activity
Authors: Zhang Yun , Li Xiaojing , Li Jia , Khan Md. Zaved Hossain , Ma Fanyi , Liu Xiuhua
Published: March 2021

Background

In order to enhance the antibacterial activity and reduce the toxicity of Zn2+, novel complexes of Zn(II) were synthesized.

Results

A water-soluble zinc-glucose-citrate complex (ZnGC) with antibacterial activity was synthesized at pH 6.5. The structure, morphology, characterization, acute toxicity, antibacterial and antioxidant activities, and in situ intestinal absorption were investigated. The results showed that zinc ion was linked with citrate by coordinate bond while the glucose was linked with it through intermolecular hydrogen bonding. The higher the molecular weight of sugar is, the more favorable it is to inhibit the formation of zinc citrate precipitation. Compared with ZnCl2, ZnGC complex presented better antibacterial activity against Staphylococcus aureus (S. aureus, Gram-positive) and Escherichia coli (E. coli, Gram-negative).

Conclusions

The results of acute toxicity showed no obvious toxicity in this test and in situ intestinal absorption study, suggesting that ZnGC complex could be used as a potential zinc supplement for zinc deficiency.
MiR-1290 promotes myoblast differentiation and protects against myotube atrophy via Akt/p70/FoxO3 pathway regulation
Authors: Che Ji , Xu Cuidi , Wu Yuanyuan , Jia Peiyu , Han Qi , Ma Yantao , Wang Xiaolei , Zheng Yongjun
Published: March 2021

Background

Sarcopenia is a common skeletal disease related to myogenic disorders and muscle atrophy. Current clinical management has limited effectiveness. We sought to investigate the role of miR-1290 in myoblast differentiation and muscle atrophy.

Methods

By transfecting miR-1290 into C2C12 cells, we investigated whether miR-1290 regulates myogenesis and myotube atrophy via AKT/P70 signaling pathway. MHC staining was performed to assess myoblast differentiation. Differentiation-related MHC, Myod, and Myog protein levels, and atrophy-related MuRF1 and atrogin-1 were explored by western blot. An LPS-induced muscle atrophy rat model was developed. RT-PCR was conducted to analyze miR-1290 serum levels in muscle atrophy patients and normal controls (NCs).

Results

The miR-1290 transfection increased MHC-positive cells and MHC, Myod, and Myog protein levels in the miR-1290 transfection group, demonstrating that miR-1290 promoted C2C12 myoblast differentiation. Myotube diameter in the miR-1290 transfection group was higher than in the TNF-α-induced model group. Western blot analysis showed decreased MuRF1 and atrogin-1 levels in the miR-1290 transfection group compared with the model group, demonstrating that miR-1290 protected against myoblast cellular atrophy. Luciferase assay and western blot analysis showed that miR-1290 regulation was likely caused by AKT/p70/FOXO3 phosphorylation activation. In the LPS-induced muscle atrophy rat model, miR-1290 mimics ameliorated gastrocnemius muscle loss and increased muscle fiber cross-sectional area. Clinically, miR-1290 serum level was significantly decreased in muscle atrophy patients.

Conclusions

We found that miR-1290 enhances myoblast differentiation and inhibits myotube atrophy through Akt/p70/FoxO3 signaling in vitro and in vivo. In addition, miR-1290 may be a potential therapeutic target for sarcopenia treatment.
Severe liver dysfunction complicating course of COVID-19 in the critically ill: multifactorial cause or direct viral effect?
Authors: Roedl Kevin , Jarczak Dominik , Drolz Andreas , Wichmann Dominic , Boenisch Olaf , de Heer Geraldine , Burdelski Christoph , Frings Daniel , Sensen Barbara , Nierhaus Axel , Lütgehetmann Marc , Kluge Stefan , Fuhrmann Valentin
Published: March 2021

Background

SARS-CoV-2 caused a pandemic and global threat for human health. Presence of liver injury was commonly reported in patients with coronavirus disease 2019 (COVID-19). However, reports on severe liver dysfunction (SLD) in critically ill with COVID-19 are lacking. We evaluated the occurrence, clinical characteristics and outcome of SLD in critically ill patients with COVID-19.

Methods

Clinical course and laboratory was analyzed from all patients with confirmed COVID-19 admitted to ICU of the university hospital. SLD was defined as: bilirubin ≥ 2 mg/dl or elevation of aminotransferase levels (> 20-fold ULN).

Results

72 critically ill patients were identified, 22 (31%) patients developed SLD. Presenting characteristics including age, gender, comorbidities as well as clinical presentation regarding COVID-19 overlapped substantially in both groups. Patients with SLD had more severe respiratory failure (paO2/FiO2: 82 (58–114) vs. 117 (83–155); p < 0.05). Thus, required more frequently mechanical ventilation (95% vs. 64%; p < 0.01), rescue therapies (ECMO) (27% vs. 12%; p = 0.106), vasopressor (95% vs. 72%; p < 0.05) and renal replacement therapy (86% vs. 30%; p < 0.001). Severity of illness was significantly higher (SAPS II: 48 (39–52) vs. 40 (32–45); p < 0.01). Patients with SLD and without presented viremic during ICU stay in 68% and 34%, respectively (p = 0.002). Occurrence of SLD was independently associated with presence of viremia [OR 6.359; 95% CI 1.336–30.253; p < 0.05] and severity of illness (SAPS II) [OR 1.078; 95% CI 1.004–1.157; p < 0.05]. Mortality was high in patients with SLD compared to other patients (68% vs. 16%, p < 0.001). After adjustment for confounders, SLD was independently associated with mortality [HR3.347; 95% CI 1.401–7.999; p < 0.01].

Conclusion

One-third of critically ill patients with COVID-19 suffer from SLD, which is associated with high mortality. Occurrence of viremia and severity of illness seem to contribute to occurrence of SLD and underline the multifactorial cause.
Instructor strategies to aid implementation of active learning: a systematic literature review
Authors: Nguyen Kevin A. , Borrego Maura , Finelli Cynthia J. , DeMonbrun Matt , Crockett Caroline , Tharayil Sneha , Shekhar Prateek , Waters Cynthia , Rosenberg Robyn
Published: March 2021

Background

Despite the evidence supporting the effectiveness of active learning in undergraduate STEM courses, the adoption of active learning has been slow. One barrier to adoption is instructors’ concerns about students’ affective and behavioral responses to active learning, especially student resistance. Numerous education researchers have documented their use of active learning in STEM classrooms. However, there is no research yet that systematically analyzes these studies for strategies to aid implementation of active learning and address students’ affective and behavioral responses. In this paper, we conduct a systematic literature review and identify 29 journal articles and conference papers that researched active learning, affective and behavioral student responses, and recommended at least one strategy for implementing active learning. In this paper, we ask: (1) What are the characteristics of studies that examine affective and behavioral outcomes of active learning and provide instructor strategies? (2) What instructor strategies to aid implementation of active learning do the authors of these studies provide?

Results

In our review, we noted that most active learning activities involved in-class problem solving within a traditional lecture-based course (N= 21). We found mostly positive affective and behavioral outcomes for students’ self-reports of learning, participation in the activities, and course satisfaction (N= 23). From our analysis of the 29 studies, we identified eight strategies to aid implementation of active learning based on three categories. Explanation strategies included providing students with clarifications and reasons for using active learning. Facilitation strategies entailed working with students and ensuring that the activity functions as intended. Planning strategies involved working outside of the class to improve the active learning experience.

Conclusion

To increase the adoption of active learning and address students’ responses to active learning, this study provides strategies to support instructors. The eight strategies are listed with evidence from numerous studies within our review on affective and behavioral responses to active learning. Future work should examine instructor strategies and their connection with other affective outcomes, such as identity, interests, and emotions.
Longitudinal multi-omics transition associated with fatality in critically ill COVID-19 patients
Authors: Sun Chaoyang , Sun Yuzhe , Wu Ping , Ding Wencheng , Wang Shiyou , Li Jiafeng , Liang Langchao , Chai Chaochao , Fu Yu , Li Zhiming , Zhu Linnan , Ju Jia , Liao Xin , Huang Xiaoyuan , Feng Ling , Ma Ding , He Liang , Chen Dongsheng , Chen Gang , Jin Xin , Wu Peng
Published: March 2021

Purpose

Critically ill COVID-19 patients have significantly increased risk of death. Although several circulating biomarkers are thought to be related to COVID-19 severity, few studies have focused on the characteristics of critically ill patients with different outcomes. The objective of this study was to perform a longitudinal investigation of the potential mechanisms affecting the prognosis of critically ill COVID-19 patients.

Methods

In addition to clinical data, 113 whole blood samples and 85 serum samples were collected from 33 severe and critical COVID-19 patients without selected comorbidities. Multi-omics analysis was then performed using longitudinal samples.

Results

Obvious transcriptional transitions were more frequent in critical survivors than in critical non-survivors, indicating that phase transition may be related to survival. Based on analysis of differentially expressed genes during transition, the erythrocyte differentiation pathway was significantly enriched. Furthermore, clinical data indicated that red blood cell counts showed greater fluctuation in survivors than in non-survivors. Moreover, declining red blood cell counts and hemoglobin levels were validated as prognostic markers of poor outcome in an independent cohort of 114 critical COVID-19 patients. Protein–metabolite–lipid network analysis indicated that tryptophan metabolism and melatonin may contribute to molecular transitions in critical COVID-19 patients with different outcomes.

Conclusions

This study systematically and comprehensively depicted the longitudinal hallmarks of critical COVID-19 patients and indicated that multi-omics transition may impact the prognosis.

Take home message

Frequent transcriptional phase transitions may contribute to outcome in critically ill COVID-19 patients. Furthermore, fluctuation in red blood cell and hemoglobin levels may relate to poor prognosis. The biological function of melatonin was suppressed in COVID-19 non-survivors, which may provide a potential theoretical basis for clinical administration.
Korea hypertension fact sheet 2020: analysis of nationwide population-based data
Authors: Kim Hyeon Chang , Cho So Mi Jemma , Lee Hokyou , Lee Hyeok-Hee , Baek Jongmin , Heo Ji Eun ,   for the Korean Society of Hypertension (KSH) – Hypertension Epidemiology Research Working Group, Kim Hyeon Chang , Ahn Song Vogue , Jee Sun Ha , Park Sungha , Lee Hae-Young , Shin Min Ho , Ihm Sang-Hyun , Lee Seung Won , Lee Hokyou , Park Jong Ku , Suh Il , Lee Tae-Yong , Cho So Mi Jemma , Lee Hyeok-Hee , Baek Jongmin , Heo Ji Eun
Published: March 2021

Background

The Korean Society of Hypertension has published the Korea Hypertension Fact Sheet 2020 to provide an overview of the magnitude and management status of hypertension and their recent trends.

Methods

The Fact Sheets were based on the analyses of Korean adults aged 20 years or older of the 2007–2018 Korea National Health and Nutrition Examination Survey (KNHANES) and the 2002–2018 National Health Insurance Big Data (NHI-BD).

Results

Currently, the population average of systolic/diastolic blood pressure was 118/76 mmHg in Korean adults aged 20 years or older showing little change in the recent decade. However, the number of people with hypertension increased steadily, exceeding 12.0 million. Indeed, the number of people diagnosed with hypertension increased from 3.0 million in 2002 to 9.7 million in 2018. During the same period, the number of people using antihypertensive medication increased from 2.5 million to 9.0 million, and the number of people adherent to treatment increased from 0.6 million to 6.5 million. Hypertension awareness, treatment, and control rates increased rapidly until 2007, but showed plateaued thereafter. In 2018, the awareness, treatment, and control rates of hypertension among all adults were 67, 63, and 47%, respectively. However, the awareness and treatment rates were only 17 and 14% among adults aged 20 to 39 years old with hypertension. Among patients treated for hypertension, 61% of them were also using glucose-lowering or lipid-lowering drugs. Among antihypertensive prescriptions, 41% of the patients received monotherapy, 43% received dual therapy, and 16% received triple or more therapy. The most commonly prescribed antihypertensive medication was angiotensin receptor blockers, followed by calcium channel blockers and diuretics.

Conclusion

To achieve further improvement in management of hypertension, we need to encourage awareness and treatment in young adults. It is required to develop tailored prevention and management strategies that are appropriate for and inclusive of various demographics.
The biosynthesis of the cannabinoids
Authors: Tahir M. Nazir , Shahbazi Fred , Rondeau-Gagné Simon , Trant John F.
Published: March 2021

Cannabis has been integral to Eurasian civilization for millennia, but a century of prohibition has limited investigation. With spreading legalization, science is pivoting to study the pharmacopeia of the cannabinoids, and a thorough understanding of their biosynthesis is required to engineer strains with specific cannabinoid profiles. This review surveys the biosynthesis and biochemistry of cannabinoids. The pathways and the enzymes’ mechanisms of action are discussed as is the non-enzymatic decarboxylation of the cannabinoic acids. There are still many gaps in our knowledge about the biosynthesis of the cannabinoids, especially for the minor components, and this review highlights the tools and approaches that will be applied to generate an improved understanding and consequent access to these potentially biomedically-relevant materials.

Graphical abstract
Post-COVID-19 encephalomyelitis
Authors: Kim Ji-Won , Abdullayev Nuran , Neuneier Janina , Fink Gereon R. , Lehmann Helmar C.
Published: March 2021

Since the outbreak of coronavirus disease 2019 (COVID-19), a growing number of cases of acute transverse myelitis associated with COVID-19 have been reported. Here, we present the case of a patient who developed sensory ataxia after COVID-19 with MR lesions suggestive for longitudinal myelitis and in the splenium of the corpus callosum. The patient was successfully treated with immunoadsorption.
The cyclase-associated protein UvCap1 is required for mycelial growth and pathogenicity in the rice false smut fungus
Authors: Cao Hui-Juan , Zhang Jin-Jin , Yong Ming-Li , Yu Mi-Na , Song Tian-Qiao , Yu Jun-Jie , Pan Xia-Yan , Liu Yong-Feng
Published: March 2021

Rice false smut caused by Ustilaginoidea virens is one of the widespread rice diseases across the globe in recent years, however, we know little about its molecular mechanism of infection. The cAMP signaling pathway functions directly in the development and formation of infectious structures to regulate the infection process in many pathogenic fungi. In order to investigate the role of the cAMP signaling pathway in U. virens, UvCap1, a cyclase-associated-protein homologous to Saccharomyces cerevisiae Srv2 was identified. Three targeted deletion mutants of the UvCAP1 gene were obtained with gene replacement strategy assisted with CRISPR-Cas9 system. The UvCAP1 deletion mutants showed defects in mycelial growth and conidial production. Inoculation experiments demonstrated that ΔUvcap1 exhibited defects in pathogenicity. Compared with the wild-type strain, ΔUvcap1 showed decreased tolerance to sorbitol and H2O2, and increased tolerance to NaCl, CFW and SDS, and the intracellular cAMP level was significantly reduced in ΔUvcap1. Yeast two-hybrid assay identified the interactions of UvCap1 with UvAc1 (adenylase cyclase), two Ras proteins (UvRas1 and UvRas2) and UvSte50. Taken together, as a component of cAMP signaling pathway, UvCap1 plays important roles in the development and pathogenicity of U. virens.
Recent advances in skin collagen: functionality and non-medical applications
Authors: Han Yanting , Hu Jinlian , Sun Gang
Published: March 2021

During nature evolution process, living organisms have gradually adapted to the environment and been adept in synthesizing high performance structural materials at mild conditions by using fairly simple building elements. The skin, as the largest organ of animals, is such a representative example. Conferred by its intricate organization where collagen fibers are arranged in a randomly interwoven network, skin collagen (SC), defined as a biomass derived from skin by removing non-collagen components displays remarkable performance with combinations of mechanical properties, chemical-reactivity and biocompatibility, which far surpasses those of synthetic materials. At present, the application of SC in medical field has been largely studied, and there have been many reviews summarizing these efforts. However, the generalized view on the aspects of SC as smart materials in non-medical fields is still lacking, although SC has shown great potential in terms of its intrinsic properties and functionality. Hence, this review will provide a comprehensive summary that integrated the recent advances in SC, including its preparation method, structure, reactivity, and functionality, as well as applications, particularly in the promising area of smart materials.

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Synthesis and application of non-bioaccumulable fluorinated surfactants: a review
Authors: Zhou Rong , Jin Yong , Shen Yichao , Zhao Peng , Zhou Yutang
Published: March 2021

Due to negative effects of conventional fluorinated surfactants with long perfluorocarbon chain (CxF2x+ 1, x≥7) like perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), these conventional long perfluorocarbon chain surfactants have been restricted in many industrial applications. Nowadays, their potential non-bioaccumulable alternatives have been developed to meet the requirements of environmental sustainable development. In this paper, the recent advances of potential non-bioaccumulable fluorinated surfactants with different fluorocarbon chain structures, including the short perfluorocarbon chain, the branched fluorocarbon chain, and the fluorocarbon chain with weak points, are reviewed from the aspects of synthesis processes, properties, and structure-activity relationships. And their applications in emulsion polymerization of fluorinated olefins, handling membrane proteins, and leather manufacture also are summarized. Furthermore, the challenges embedded in the current non-bioaccumulable fluorinated surfactants are also highlighted and discussed with the hope to provide a valuable reference for the prosperous development of fluorinated surfactants.

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Multi-grade fuzzy assessment framework for software professionals in work-from-home mode during and post-COVID-19 era
Authors: Suresh M. , Gopakumar Kavya
Published: March 2021

The pandemic novel Coronavirus disease and the resulting lockdowns have contributed to major economic disturbances around the world, forcing organisations to extend the work-from-home (WFH) option to their employees wherever feasible. The current major challenge of this option is maintaining the efficiency and productivity of the employees across the organisations. It is therefore important to understand the impact of this make-shift arrangement of WFH policy and their underlying effects that may affect the efficiency of employees and hence their output levels. This is a distinctive approach to develop a unique framework for efficiency index computation by evaluating the efficiency levels of WFH mode in software organisations using multi-grade fuzzy approach and importance–performance analysis. In turn, this would help to determine the crucial attributes that require improvement to increase the efficiency levels of employees concerned. In this study, a case project has been assessed and it was observed that the efficiency index of WFH accounts to 4.92, which is in between the range of (4.01–6) specified as ‘Efficient’. The framework can be used on a periodic basis to help software organisations to continuously improve their WFH efficiency level.
Scholarly Activity of Radiation Oncologists in High-Income Developing Countries: Saudi Arabia as an Example
Authors: Alghamdi Majed A. , Alghamdi Suliman M. , Bahadur Yasir A. , Asiri Mushabbab A. , AlHussain Hussain A. , Alhebshi Adnan S. , Alothman Majid O. , Al-omair Ameen S. , Alghamdi Abdulaziz A. , Qanat Ahmed S. , Aqeeli Mohammed O. , Alsuhaibani Abdullah A. , Alshehri Salem M. , Alotain Ibrahim M. , Mail Noor K. , Alhashemi Hashem H. , Alassaf Hossam A.
Published: March 2021

PURPOSE

To examine the trends and quality metrics of publications by radiation oncologists in Saudi Arabia.

METHODS

PubMed was searched using names of all Saudi radiation oncologists to retrieve published articles between January 2010 and December 2019. International collaboration, journal impact factor and country of origin, and number of citations were collected. Each article was assessed for epidemiologic type and independently assigned a level of evidence (LOE) by two authors. The trend in publications was examined and compared in the first and second 5-year periods (2010-2014 and 2015-2019) using relevant parameters.

RESULTS

A total of 186 publications were found and included. The most common type of research was cohort studies followed by case reports and case series in 24%, 14%, and 13% of all publications, respectively. Dosimetry, clinical, and preclinical studies formed 7%, 8.6%, and 7.5% of the total publications, respectively. The LOE was I, II, III, IV, and not applicable in 8.6%, 22%, 25.8%, 29%, and 14.5% of the included publications, respectively. Comparing the first and second 5-year periods, there was an increase in international collaboration ( P < .001) in the second period. The number of citations ( P < .001) and journal impact factor ( P = .028) were lower in the second period. LOE and publications in international journals were not statistically different between the two periods.

CONCLUSION

Although radiation oncology research activity in Saudi Arabia has gained momentum in terms of volume and international collaboration over time, the LOE has not improved. This calls for a national effort to make the contribution to the literature a priority, allocate adequate resources, and apply appropriate measures to enhance research productivity and quality.
Never Enough Time: Mixed Methods Study Identifies Drivers of Temporal Demand That Contribute to Burnout Among Physicians Who Care for Pediatric Hematology-Oncology Patients
Authors: Blazin Lindsay J. , Terao Michael A. , Spraker-Perlman Holly , Baker Justin N. , McLaughlin Crabtree Valerie , Mandrell Belinda N. , Gattuso Jami , Sellers Janet , Dunn Tyler J. , Lu Zhaohua , Hoffman James M. , Burlison Jonathan D.
Published: March 2021

PURPOSE:

Burnout is a syndrome of emotional exhaustion, depersonalization, and reduced personal accomplishment because of chronic occupational stress. Approximately one third of pediatric hematology-oncology physicians experience burnout. The goal of this mixed methods study was to determine the prevalence and drivers of burnout among physicians caring for pediatric hematology-oncology patients at our institution.

MATERIALS AND METHODS:

This mixed methods, cross-sectional study was conducted at a large academic cancer center. Validated survey instruments were used to measure burnout, job demands, experience with patient safety events, and workplace culture. Quantitative data informed development of a semistructured interview guide, and physicians were randomly selected to participate in individual interviews. Interviews were transcribed and analyzed via content analysis based on a priori codes.

RESULTS:

The survey was distributed to 132 physicians, and 53 complete responses were received (response rate 40%). Of the 53 respondents, 15 (28%) met criteria for burnout. Experiencing burnout was associated with increased temporal demand. Twenty-six interviews were conducted. Qualitative themes revealed that frequent meetings, insufficient support staff, and workflow interruptions were key drivers of temporal demand and that temporal demand contributed to burnout through emotional exhaustion and reduced personal accomplishment.

CONCLUSION:

Nearly one-third of participating physicians met criteria for burnout, and burnout was associated with increased temporal demand. Qualitative interviews identified specific drivers of temporal demand and burnout, which can be targeted for intervention. This methodology can be easily adapted for broad use and may represent an effective strategy for identifying and mitigating institution-specific drivers of burnout.
Deiodinases and the Metabolic Code for Thyroid Hormone Action
Authors: Russo Samuel C , Salas-Lucia Federico , Bianco Antonio C
Published: March 2021

Deiodinases modify the biological activity of thyroid hormone (TH) molecules, ie, they may activate thyroxine (T4) to 3,5,3′-triiodothyronine (T3), or they may inactivate T3 to 3,3′-diiodo-L-thyronine (T2) or T4 to reverse triiodothyronine (rT3). Although evidence of deiodination of T4 to T3 has been available since the 1950s, objective evidence of TH metabolism was not established until the 1970s. The modern paradigm considers that the deiodinases not only play a role in the homeostasis of circulating T3, but they also provide dynamic control of TH signaling: cells that express the activating type 2 deiodinase (D2) have enhanced TH signaling due to intracellular build-up of T3; the opposite is seen in cells that express type 3 deiodinase (D3), the inactivating deiodinase. D2 and D3 are expressed in metabolically relevant tissues such as brown adipose tissue, skeletal muscle and liver, and their roles have been investigated using cell, animal, and human models. During development, D2 and D3 expression customize for each tissue/organ the timing and intensity of TH signaling. In adult cells, D2 is induced by cyclic adenosine monophosphate (cAMP), and its expression is invariably associated with enhanced T3 signaling, expression of PGC1 and accelerated energy expenditure. In contrast, D3 expression is induced by hypoxia-inducible factor 1α (HIF-1a), dampening T3 signaling and the metabolic rate. The coordinated expression of these enzymes adjusts TH signaling in a time- and tissue-specific fashion, affecting metabolic pathways in health and disease states.