bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Proteomic Analysis of Polarized Human THP-1 and Mouse RAW264.7 Macrophages
Authors: Li Pengfei , Hao Zhifang , Wu Jingyu , Ma Chen , Xu Yintai , Li Jun , Lan Rongxia , Zhu Bojing , Ren Pengyu , Fan Daidi , Sun Shisheng
Published: June 2021

Macrophages can be polarized into classically activated macrophages (M1) and alternatively activated macrophages (M2) in the immune system, performing pro-inflammatory and anti-inflammatory functions, respectively. Human THP-1 and mouse RAW264.7 cell line models have been widely used in various macrophage-associated studies, while the similarities and differences in protein expression profiles between the two macrophage models are still largely unclear. In this study, the protein expression profiles of M1 and M2 phenotypes from both THP-1 and RAW264.7 macrophages were systematically investigated using mass spectrometry-based proteomics. By quantitatively analyzing more than 5,000 proteins among different types of macrophages (M0, M1 and M2) from both cell lines, we identified a list of proteins that were uniquely up-regulated in each macrophage type and further confirmed 43 proteins that were commonly up-regulated in M1 macrophages of both cell lines. These results revealed considerable divergences of each polarization type between THP-1 and RAW264.7 macrophages. Moreover, the mRNA and protein expression of CMPK2, RSAD2, DDX58, and DHX58 were strongly up-regulated in M1 macrophages for both macrophage models. These data can serve as important resources for further studies of macrophage-associated diseases in experimental pathology using human and mouse cell line models.
Changes in Underwater Noise and Vessel Traffic in the Approaches to Halifax Harbor, Nova Scotia, Canada
Authors: Breeze Heather , Li Shihan , Marotte Emmaline C. , Theriault James A. , Wingfield Jessica , Xu Jinshan
Published: June 2021

Over the past two years, researchers at Fisheries and Oceans Canada have been running an acoustic monitoring project at multiple study sites throughout Nova Scotia, Canada to investigate baleen whale presence and levels of underwater noise. At the onset of the COVID-19 pandemic, a passive acoustic monitor (PAM) was in place in the study site located in the approaches to Halifax Harbor, a major Canadian port. This provided a unique opportunity to determine if changes in vessel noise levels occurred after pandemic restrictions were put in place. To investigate this, we analyzed and compared acoustic data collected from March 28 to April 28 and August 6 to October 22 in both 2019 and 2020. We also investigated possible changes in vessel traffic from February 1 through April 28 and July 1 through July 28 in 2019 and 2020 using terrestrial-based automatic identification system (AIS) data provided by the Canadian Coast Guard and cargo information provided by the Port of Halifax. The acoustic data were analyzed in 1/3 octave frequency bands. For the 89.1–112 Hz frequency band, we found an 8.4 dB increase in the daily minimum sound pressure level (SPL) in April 2020 compared to April 2019 due the presence of a large crane vessel stationed near the mooring site. For the period of August to October, we found an approximately 1.7 dB reduction in the same metric from 2019 to 2020. The most noticeable change in vessel composition was the dramatic decrease in the number and occurrence of pleasure craft in July 2020 compared to the same period in 2019. While this analysis looked at only a single PAM and a limited amount of data, we observed changes in sound levels in the frequency band known to be associated with shipping as well as changes in vessel traffic; we conclude that these observed changes may be related to pandemic restrictions.
Gene Expression Response to Stony Coral Tissue Loss Disease Transmission in M. cavernosa and O. faveolata From Florida
Authors: Traylor-Knowles Nikki , Connelly Michael T. , Young Benjamin D. , Eaton Katherine , Muller Erinn M. , Paul Valerie J. , Ushijima Blake , DeMerlis Allyson , Drown Melissa K. , Goncalves Ashley , Kron Nicholas , Snyder Grace A. , Martin Cecily , Rodriguez Kevin
Published: June 2021

Since 2014, corals within Florida’s Coral Reef have been dying at an unprecedented rate due to stony coral tissue loss disease (SCTLD). Here we describe the transcriptomic outcomes of three different SCTLD transmission experiments performed at the Smithsonian Marine Station and Mote Marine Laboratory between 2019 and 2020 on the corals Orbicella faveolata and Montastraea cavernosa. Overall, diseased O. faveolata had 2194 differentially expressed genes (DEGs) compared with healthy colonies, whereas diseased M. cavernosa had 582 DEGs compared with healthy colonies. Many significant DEGs were implicated in immunity, extracellular matrix rearrangement, and apoptosis. These included, but not limited to, peroxidases, collagens, Bax-like, fibrinogen-like, protein tyrosine kinase, and transforming growth factor beta. A gene module was identified that was significantly correlated to disease transmission. This module possessed many apoptosis and immune genes with high module membership indicating that a complex apoptosis and immune response is occurring in corals during SCTLD transmission. Overall, we found that O. faveolata and M. cavernosa exhibit an immune, apoptosis, and tissue rearrangement response to SCTLD. We propose that future studies should focus on examining early time points of infection, before the presence of lesions, to understand the activating mechanisms involved in SCTLD.
Updated Evidence of the Association Between Elevated Serum Uric Acid Level and Psoriasis
Authors: Zhang Ying , Liu Liu , Sun Xiaoying , Li Hongjin , Wang Yifei , Zhou Min , Hua Liang , Li Bin , Li Xin
Published: June 2021

Background: Our earlier meta-analysis showed that the correlation between psoriasis and hyperuricemia might be region-dependent and that hyperuricemia was more common in patients with psoriasis in Western Europe. However, no further analysis could be conducted owing to the scarcity of data.

Objective: Our study aimed to further explore the association between psoriasis and hyperuricemia.

Methods: Six databases (PubMed, Embase, the Cochrane Central Register of Controlled Trials, the China National Knowledge Infrastructure database, the Chinese Scientific Journals Full Text Database, and the Wanfang Data Knowledge Service Platform) were searched for studies published between January 1980 and February 2021.

Results: The search strategy yielded 291 relevant studies, of which 27 observational studies were included in this analysis. Serum uric acid (SUA) levels (mean difference [MD] 0.99, 95% confidence interval [CI] 0.48–1.49, P = 0.0001) and hyperuricemia frequency (odds ratio [OR] 5.39, 95% CI 1.88–15.40, P = 0.002) were higher in the psoriasis group than in the control group, and the subgroup differences were significant. In addition, SUA levels were significantly higher in patients with moderate to severe psoriasis from European and American countries (MD 0.89, 95% CI 0.18–1.60, P = 0.01) and Southeast Asia (MD 1.79, 95% CI 0.55–3.02, P = 0.004), while no significant differences were found between the Middle East subgroup (MD 0.63, 95% CI −0.33 to 1.59, P = 0.20). Similar results were obtained from the meta-analysis of SUA levels in patients with metabolic syndrome, obesity, or a special type of psoriasis (such as arthritic or erythrodermic psoriasis).

Conclusions: Our meta-analysis study provides extended data regarding the correlation between psoriasis and hyperuricemia and the differences in SUA levels between psoriasis patients and controls in Southeast Asia, the Middle East, and European and American countries. Patients with moderate to severe psoriasis in European and American countries and Southeast Asia or those with metabolic syndrome and obesity were more likely to have higher uric acid levels.

Systematic Review Registration: PROSPERO, identifier: CRD42014015091.
Widespread Parenchymal Abnormalities and Pulmonary Embolism on Contrast-Enhanced CT Predict Disease Severity and Mortality in Hospitalized COVID-19 Patients
Authors: Jalde Francesca Campoccia , Beckman Mats O. , Svensson Ann Mari , Bell Max , Sköld Magnus , Strand Fredrik , Nyren Sven , Kistner Anna
Published: June 2021

Purpose: Severe COVID-19 is associated with inflammation, thromboembolic disease, and high mortality. We studied factors associated with fatal outcomes in consecutive COVID-19 patients examined by computed tomography pulmonary angiogram (CTPA).

Methods: This retrospective, single-center cohort analysis included 130 PCR-positive patients hospitalized for COVID-19 [35 women and 95 men, median age 57 years (interquartile range 51–64)] with suspected pulmonary embolism based on clinical suspicion. The presence and extent of embolism and parenchymal abnormalities on CTPA were recorded. The severity of pulmonary parenchymal involvement was stratified by two experienced radiologists into two groups: lesions affecting ≤50% or >50% of the parenchyma. Patient characteristics, radiological aspects, laboratory parameters, and 60-day mortality data were collected.

Results: Pulmonary embolism was present in 26% of the patients. Most emboli were small and peripheral. Patients with widespread parenchymal abnormalities, with or without pulmonary embolism, had increased main pulmonary artery diameter (p < 0.05) and higher C-reactive protein (p < 0.01), D-dimer (p < 0.01), and troponin T (p < 0.001) and lower hemoglobin (p < 0.001). A wider main pulmonary artery diameter correlated positively with C-reactive protein (r = 0.28, p = 0.001, and n = 130) and procalcitonin. In a multivariant analysis, D-dimer >7.2 mg/L [odds ratio (±95% confidence interval) 4.1 (1.4–12.0)] and ICU stay were significantly associated with embolism (p < 0.001). The highest 60-day mortality was found in patients with widespread parenchymal abnormalities combined with pulmonary embolism (36%), followed by patients with widespread parenchymal abnormalities without pulmonary embolism (26%). In multivariate analysis, high troponin T, D-dimer, and plasma creatinine and widespread parenchymal abnormalities on CT were associated with 60-day mortality.

Conclusions: Pulmonary embolism combined with widespread parenchymal abnormalities contributed to mortality risk in COVID-19. Elevated C-reactive protein, D-dimer, troponin-T, P-creatinine, and enlarged pulmonary artery were associated with a worse outcome and may mirror a more severe systemic disease. A liberal approach to radiological investigation should be recommended at clinical deterioration, when the situation allows it. Computed tomography imaging, even without intravenous contrast to assess the severity of pulmonary infiltrates, are of value to predict outcome in COVID-19. Better radiological techniques with higher resolution could potentially improve the detection of microthromboses. This could influence anticoagulant treatment strategies, preventing clinical detoriation.
New Pandemic: Obesity and Associated Nephropathy
Authors: Sharma Isha , Liao Yingjun , Zheng Xiaoping , Kanwar Yashpal S.
Published: June 2021

Incidence of obesity related renal disorders have increased 10-folds in recent years. One of the consequences of obesity is an increased glomerular filtration rate (GFR) that leads to the enlargement of the renal glomerulus, i.e., glomerulomegaly. This heightened hyper-filtration in the setting of type 2 diabetes irreparably damages the kidney and leads to progression of end stage renal disease (ESRD). The patients suffering from type 2 diabetes have progressive proteinuria, and eventually one third of them develop chronic kidney disease (CKD) and ESRD. For ameliorating the progression of CKD, inhibitors of renin angiotensin aldosterone system (RAAS) seemed to be effective, but on a short-term basis only. Long term and stable treatment strategies like weight loss via restricted or hypo-caloric diet or bariatric surgery have yielded better promising results in terms of amelioration of proteinuria and maintenance of normal GFR. Body mass index (BMI) is considered as a traditional marker for the onset of obesity, but apparently, it is not a reliable indicator, and thus there is a need for more precise evaluation of regional fat distribution and amount of muscle mass. With respect to the pathogenesis, recent investigations have suggested perturbation in fatty acid and cholesterol metabolism as the critical mediators in ectopic renal lipid accumulation associated with inflammation, increased generation of ROS, RAAS activation and consequential tubulo-interstitial injury. This review summarizes the renewed approaches for the obesity assessment and evaluation of the pathogenesis of CKD, altered renal hemodynamics and potential therapeutic targets.
Bioinformatic Analysis of the Campylobacter jejuni Type VI Secretion System and Effector Prediction
Authors: Robinson Luca , Liaw Janie , Omole Zahra , Xia Dong , van Vliet Arnoud H. M. , Corcionivoschi Nicolae , Hachani Abderrahman , Gundogdu Ozan
Published: June 2021

The Type VI Secretion System (T6SS) has important roles relating to bacterial antagonism, subversion of host cells, and niche colonisation. Campylobacter jejuni is one of the leading bacterial causes of human gastroenteritis worldwide and is a commensal coloniser of birds. Although recently discovered, the T6SS biological functions and identities of its effectors are still poorly defined in C. jejuni. Here, we perform a comprehensive bioinformatic analysis of the C. jejuni T6SS by investigating the prevalence and genetic architecture of the T6SS in 513 publicly available genomes using C. jejuni 488 strain as reference. A unique and conserved T6SS cluster associated with the Campylobacter jejuni Integrated Element 3 (CJIE3) was identified in the genomes of 117 strains. Analyses of the T6SS-positive 488 strain against the T6SS-negative C. jejuni RM1221 strain and the T6SS-positive plasmid pCJDM202 carried by C. jejuni WP2-202 strain defined the “T6SS-containing CJIE3” as a pathogenicity island, thus renamed as Campylobacter jejuni Pathogenicity Island-1 (CJPI-1). Analysis of CJPI-1 revealed two canonical VgrG homologues, CJ488_0978 and CJ488_0998, harbouring distinct C-termini in a genetically variable region downstream of the T6SS operon. CJPI-1 was also found to carry a putative DinJ-YafQ Type II toxin-antitoxin (TA) module, conserved across pCJDM202 and the genomic island CJIE3, as well as several open reading frames functionally predicted to encode for nucleases, lipases, and peptidoglycan hydrolases. This comprehensive in silico study provides a framework for experimental characterisation of T6SS-related effectors and TA modules in C. jejuni.
Validating Habitual and Goal-Directed Decision-Making Performance Online in Healthy Older Adults
Authors: Ito Kaori L. , Cao Laura , Reinberg Renee , Keller Brenton , Monterosso John , Schweighofer Nicolas , Liew Sook-Lei
Published: June 2021

Everyday decision-making is supported by a dual-system of control comprised of parallel goal-directed and habitual systems. Over the past decade, the two-stage Markov decision task has become popularized for its ability to dissociate between goal-directed and habitual decision-making. While a handful of studies have implemented decision-making tasks online, only one study has validated the task by comparing in-person and web-based performance on the two-stage task in children and young adults. To date, no study has validated the dissociation of goal-directed and habitual behaviors in older adults online. Here, we implemented and validated a web-based version of the two-stage Markov task using parameter simulation and recovery and compared behavioral results from online and in-person participation on the two-stage task in both young and healthy older adults. We found no differences in estimated free parameters between online and in-person participation on the two-stage task. Further, we replicate previous findings that young adults are more goal-directed than older adults both in-person and online. Overall, this work demonstrates that the implementation and use of the two-stage Markov decision task for remote participation is feasible in the older adult demographic, which would allow for the study of decision-making with larger and more diverse samples.
Validation of Blood Pressure Measurement Using a Smartwatch in Patients With Parkinson's Disease
Authors: Ahn Jong Hyeon , Song Joomee , Choi Inyoung , Youn Jinyoung , Cho Jin Whan
Published: June 2021

Objectives: We aimed to validate the accuracy of blood pressure (BP) measurement using a smartwatch in patients with Parkinson's disease (PD).

Materials and Methods: We compared 168 pairs of BP (n = 56) measurements acquired by a smartwatch (SM-R850) with those measured by a sphygmomanometer (reference device).

Results: Differences between the smartwatch BP and reference BP measurements were compared. The mean and standard deviation of the differences systolic BP (SBP) and diastolic BP (DBP), measured by smartwatch and reference device, fulfilled both criterion 1 (0.4 ± 4.6 and 1.1 ± 4.5 mm Hg for DBP and SBP, respectively) and criterion 2 (0.2 ± 2.5 and 0.9 ± 2.4 mm Hg for DBP and SBP, respectively) of the BP validation criterion of the International Organization for Standardization.

Conclusion: BP measurement using a smartwatch with a photoplethysmography sensor is an accurate and reliable method in patients with PD.
Dancing Improves Emotional Regulation in Women With Methamphetamine Use Disorder But Use of a Cycle Ergometer Does Not
Authors: Tao Qian , Zhang Chenping , Li Xiawen
Published: June 2021

Background

Emotional regulation is crucial to people who receive a diagnosis of methamphetamine (MA) use disorder. Although evidence that exercise improves emotional regulation is robust, little is known about whether exercise will improve emotional processing in women with MA use disorder.

Methods

In the present study, 36 women with MA use disorder aged 20 to 34 years and residing in the Drug Rehabilitation Bureau of Mogan Mountain in Zhejiang province were assigned to 1 of 2 exercise intervention groups-dancing or stationary cycling. Both types of exercise were performed at 65–75% of the maximum heart rate for 30 min. Immediately before and after the exercise bout, the participants were asked to score their feelings using a nine-point Likert scale as they viewed emotionally negative, positive, or neutral images in blocks of 20 images each, for a total of 60 images. Concurrent with viewing the images and self-rating their emotions, the women also underwent functional near-infrared spectroscopy to assess changes in brain activity.

Results

There were no significant differences in the demographic or MA use characteristics assessed for the women between the two exercise groups. We found main effect of image valence (F2,33= 69.61,p< 0.01), significant interaction effect of time and image valence was found (F2,33= 4.27,p< 0.05) and trend increase in the self-rated emotional scale score for viewing negative images in both groups after 30-min exercise intervention, and the dancing group presented more significant trends than cycling group. In addition, activation in the dorsolateral prefrontal cortex of dancers, but not of cyclists, while viewing negative images was significantly lower after vs. before dancing (F2,33= 5.43,p< 0.05). This result suggested that 30 min of dancing decreased neural activity in women with MA use disorder while they viewed negative images specifically in a brain region known to guide the selection of appropriate behaviors, and to shift attention.

Taken together, the findings of this study suggest that for women with MA abuse disorder, 30 min of dancing, rather than of stationary cycling, may ameliorate negative emotional reactions by decreasing attention to negative stimuli.
Keeping the Breath in Mind: Respiration, Neural Oscillations, and the Free Energy Principle
Authors: Boyadzhieva Asena , Kayhan Ezgi
Published: June 2021

Scientific interest in the brain and body interactions has been surging in recent years. One fundamental yet underexplored aspect of brain and body interactions is the link between the respiratory and the nervous systems. In this article, we give an overview of the emerging literature on how respiration modulates neural, cognitive and emotional processes. Moreover, we present a perspective linking respiration to the free-energy principle. We frame volitional modulation of the breath as an active inference mechanism in which sensory evidence is recontextualized to alter interoceptive models. We further propose that respiration-entrained gamma oscillations may reflect the propagation of prediction errors from the sensory level up to cortical regions in order to alter higher level predictions. Accordingly, controlled breathing emerges as an easily accessible tool for emotional, cognitive, and physiological regulation.
Investigations on the Role of the MicroRNA-338-5p/Wnt Family Member 2B (WNT2B) Axis in Regulating the Pathogenesis of Nasopharyngeal Carcinoma (NPC)
Authors: Wang Suzhen , Yang Tianning , He Zhengxiang
Published: June 2021

Background

The involvement of microRNA-338-5p in modulating NPC pathogenesis is still largely unknown, and this study aimed to investigate this issue.

Methods

The expressions of cancer associated genes were determined by Real-Time qPCR and Western Blot, and cell apoptosis was determined by flow cytometer (FCM). CCK-8 assay and colony formation assay were respectively used to determine cell proliferation and colony formation abilities. Transwell assay was used to evaluate cell migration. The expression levels of Ki67 protein in mice tissues were measured by Immunohistochemistry (IHC) assay.

Results

The present study found that microRNA-338-5p suppressed NPC progression by degrading its downstream target, Wnt family member 2B (WNT2B). Specifically, microRNA-338-5p tended to be low-expressed in NPC tissues and cell lines, compared to the non-tumor nasopharyngeal mucosa tissues and normal nasopharyngeal cell line (NP69). Upregulation of microRNA-338-5p inhibited proliferation, mobility, and epithelial-mesenchymal transition (EMT) in NPC cells in vitro, while silencing of microRNA-338-5p had opposite effects. Consistently, microRNA-338-5p suppressed tumorigenesis of NPC cells in vivo. In addition, microRNA-338-5p targeted WNT2B for degradation and inhibition, and the inhibiting effects of microRNA-338-5p overexpression on NPC development were reversed by upregulating WNT2B.

Conclusions

Taken together, we concluded that microRNA-338-5p targeted WNT2B to hinder NPC development.
Case Report: Very Late, Atypical Extra-Medullary Relapse in a Patient With Acute Promyelocytic Leukemia (APL) Rescued With a Transplant-Free Approach
Authors: Molica Matteo , Mazzone Carla , Ottone Tiziana , Niscola Pasquale , Abruzzese Elisabetta , Fratoni Stefano , Voso Maria Teresa , de Fabritiis Paolo
Published: June 2021

Relapses of acute promyelocytic leukemia (APL) beyond 7 years from the first molecular remission are exceptional, and it is unclear whether these relapses represent a new, therapy-related leukemia rather than a delayed relapse of the original leukemic clone. The increase extra-medullary relapses (ER) in the era of all-trans retinoic acid (ATRA) therapy suggests a potential correlation between ATRA therapy and ER, and several potential explanations have been proposed. The gold standard post-remission approach, particularly for patients in late relapse, has not yet been established. The benefit of a transplant approach has been questioned in this setting because continuing ATRA-arsenic trioxide (ATO) might be curative. Here we report on the case of an APL patient who relapsed 9 years after achieving her first molecular complete remission (mCR) and who showed an atypical isolated localization at nodal sites, including the into- and peri-parotid glands. Genomic PML/RARa breakpoint analysis detected the same bcr3 PML/RARa hybrid gene in DNA purified from bone marrow and lymph nodes, suggesting that the relapse was because of the reemergence of the initial clone. This case shows that APL, treated with ATRA and cytotoxic drugs, may still emerge in extra-medullary sites even after a very prolonged mCR and could be salvaged with an ATO-based protocol, not including a transplant approach.
Case Report: BCG-Triggered Hemophagocytic Lymphohistiocytosis in an Infant With X-Linked Recessive Mendelian Susceptibility to Mycobacterial Disease Due to a Variant of Chronic Granulomatous Disease
Authors: Al-Hammadi Suleiman , Yahya Amal M. , Al-Amri Abdulla , Shibli Amar , Balhaj Ghazala B. , Tawil Mohamed I. , Vijayan Ranjit , Souid Abdul-Kader
Published: June 2021

In the United Arab Emirates, BCG (Bacillus Calmette-Guérin) is administered to all newborns. We present here a young infant with an inborn error of immunity (IEI) who developed fatal adverse events to this live-attenuated vaccine. This male infant received BCG (Serum Institute of India Pvt., Ltd., India) on Day 11 of life. On Day 25, he developed fever, followed by cervical lymphadenitis and bilateral otitis media with fluid drainage. On Day 118, he was admitted with severe hemophagocytic lymphohistiocytosis (HLH), and passed away on Day 145. The diagnostic exome sequencing test identified a hemizygous nonsense variant, NM_000397.3(CYBB):c.676C>T, p.Arg226* (rs137854592). Pathogenic variants of CYBB [cytochrome b(-245), beta subunit; Mendelian Inheritance in Man [MIM] accession code, 300481] are known to cause “immunodeficiency 34, mycobacteriosis, X-linked” (IMD34, MIM#300645) and “chronic granulomatous disease, X-linked” (CGDX, MIM#306400). The natural history of his illness is consistent with “X-linked recessive Mendelian susceptibility to mycobacterial disease (MSMD).” This entity is responsible for his BCG disease and is a likely trigger of his HLH. This disastrous event underlines the importance of developing worldwide policies that target BCG disease prevention, especially in communities with high prevalence of IEI. Moreover, screening for genetic causes of MSMD in the community could pave the way, at least partially, for scale-up of tuberculosis (TB) prevention.
Analysis of Suspension of Clinical Trials for Drug Registration in China
Authors: Su Xian , Pang Xiaocong , Zeng Xin , Gao Yi , Cui Yimin , Wang Haixue
Published: June 2021

Suspension is an important risk control measure during clinical trials. We investigated the use of this in China and identified common reasons for suspension by analyzing trends, hold issues, outcomes, background and design characteristics of suspended clinical drug trials from January 1, 2013 to December 1, 2019. A total of 298 clinical trials during the study timeframe were registered, accounting for 3.1% of all clinical drug trials. Numbers and proportion of clinical trials suspended based on benefit/risk factors have been increasing without holds on registrations by Center for Drug Evaluation. Reasons for suspension vary among trial phases, benefit and risk factors, protocol issues etc. 67% of trials that have been on hold for >1 year were still on hold at the time of this analysis. Children and the elderly were enrolled in 4.1% and 41% of the suspended trials, respectively. Strengthening regulation of pre-market pharmacovigilance through optimizing reporting and monitoring of safety information during clinical trial is thus needed. Establishing a closed-loop treatment mechanism for trial suspension is also important. Examination of potential risks, such as the quality of protocols, the ability of the institution to support the trial, and the adequacy of supplies of the investigational product is needed before beginning clinical trials. More careful evaluation at the drug registration phase will reduce the frequency of suspension and protect subjects after suspension occurs.
Combination Treatment With Inhibitors of ERK and Autophagy Enhances Antitumor Activity of Betulinic Acid in Non–small-Cell Lung Cancer In Vivo and In Vitro
Authors: Sun Chao-Yue , Cao Di , Ren Qian-Nan , Zhang Shan-Shan , Zhou Ning-Ning , Mai Shi-Juan , Feng Bing , Wang Hui-Yun
Published: June 2021

Aberrant activation of the Ras–ERK signaling pathway drives many important cancer phenotypes, and several inhibitors targeting such pathways are under investigation and/or approved by the FDA as single- or multi-agent therapy for patients with melanoma and non–small-cell lung cancer (NSCLC). Here, we show that betulinic acid (BA), a natural pentacyclic triterpenoid, inhibits cell proliferation, and induces apoptosis and protective autophagy in NSCLC cells. Thus, the cancer cell killing activity of BA is enhanced by autophagy inhibition. Mitogen-activated protein kinases, and especially ERK that facilitates cancer cell survival, are also activated by BA treatment. As such, in the presence of ERK inhibitors (ERKi), lung cancer cells are much more sensitive to BA. However, the dual treatment of BA and ERKi results in increased protective autophagy and AKT phosphorylation. Accordingly, inhibition of AKT has a highly synergistic anticancer effect with co-treatment of BA and ERKi. Notably, autophagy inhibition by hydroxychloroquine (HCQ) increases the response of lung cancer cells to BA in combination with ERKi. In vivo, the three-drug combination (BA, ERKi, and HCQ), resulted in superior therapeutic efficacy than single or dual treatments in the xenograft mouse model. Thus, our study provides a combined therapy strategy that is a highly effective treatment for patients with NSCLC.
Microscopic Mass Spectrometry Imaging Reveals the Distribution of Phytochemicals in the Dried Root of Isatis tinctoria
Authors: Nie Li-Xing , Dong Jing , Huang Lie-Yan , Qian Xiu-Yu , Lian Chao-Jie , Kang Shuai , Dai Zhong , Ma Shuang-Cheng
Published: June 2021

The dried root of Isatis tinctoria L. (Brassicaceae) is one of the most popular traditional Chinese medicines with well-recognized prevention and treatment effects against viral infections. Above 300 components have been isolated from this herb, but their spatial distribution in the root tissue remains unknown. In recent years, mass spectrometry imaging (MSI) has become a booming technology for capturing the spatial accumulation and localization of molecules in fresh plants, animal, or human tissues. However, few studies were conducted on the dried herbal materials due to the obstacles in cryosectioning. In this study, distribution of phytochemicals in the dried root of Isatis tinctoria was revealed by microscopic mass spectrometry imaging, with application of atmospheric pressure–matrix-assisted laser desorption/ionization (AP-MALDI) and ion trap–time-of-flight mass spectrometry (IT-TOF/MS). After optimization of the slice preparation and matrix application, 118 ions were identified without extraction and isolation, and the locations of some metabolites in the dried root of Isatis tinctoria were comprehensively visualized for the first time. Combining with partial least square (PLS) regression, samples collected from four habitats were differentiated unambiguously based on their mass spectrometry imaging.
Inhaled Corticosteroids and the Pneumonia Risk in Patients With Chronic Obstructive Pulmonary Disease: A Meta-analysis of Randomized Controlled Trials
Authors: Chen Hong , Sun Jian , Huang Qiang , Liu Yongqi , Yuan Mengxin , Ma Chunlan , Yan Hao
Published: June 2021

Background: Whether all types of inhaled corticosteroids (ICSs) would increase the pneumonia risk in patients with chronic obstructive pulmonary disease (COPD) remains controversial. We aimed to assess the association between ICSs treatment and pneumonia risk in COPD patients, and the impact of medication details and baseline characteristics of patients on the association.

Methods: Four databases (PubMed, Embase, Cochrane Library, and Clinical Trials.gov) were searched to identify eligible randomized controlled trials (RCTs) comparing ICSs treatment with non-ICSs treatment on the pneumonia risk in COPD patients. Pooled results were calculated using Peto odds ratios (Peto ORs) with corresponding 95% confidence intervals (CIs).

Results: A total of 59 RCTs enrolling 103,477 patients were analyzed. All types of ICSs significantly increased the pneumonia risk (Peto OR, 1.43; 95% CI, 1.34–1.53). Subgroup analysis showed that there was a dose-response relationship between ICSs treatment and pneumonia risk (low-dose: Peto OR, 1.33; 95% CI, 1.22–1.45; medium-dose: Peto OR, 1.50; 95% CI, 1.28–1.76; and high-dose: Peto OR, 1.64; 95% CI, 1.45–1.85). Subgroup analyses based on treatment durations and baseline characteristics (severity, age, and body mass index) of patients were consistant with the above results. Subgroup analysis based on severity of pneumonia showed that fluticasone (Peto OR, 1.75; 95% CI, 1.44–2.14) increased the risk of serious pneumonia, while budesonide and beclomethasone did not.

Conclusions: ICSs treatment significantly increased the risk of pneumonia in COPD patients. There was a dose-response relationship between ICSs treatment and pneumonia risk. The pneumonia risk was related with COPD severity.
Profiling and Molecular Mechanism Analysis of Long Non-Coding RNAs and mRNAs in Pulmonary Arterial Hypertension Rat Models
Authors: Hou Shiqiang , Chen Dandan , Liu Jie , Chen Shasha , Zhang Xiaochun , Zhang Yuan , Li Mingfei , Pan Wenzhi , Zhou Daxin , Guan Lihua , Ge Junbo
Published: June 2021

Pulmonary arterial hypertension (PAH) is an immune-mediated disease with poor prognosis and associated with various inflammatory immune diseases. In fact, its pathogenesis is far from clear. Although long non-coding RNAs (lncRNAs) have been implicated in PAH, the molecular mechanisms remain largely unknown. For the first time, in lungs of monocrotaline-induced PAH rat models, we simultaneously detected the expression profiles of lncRNAs and mRNAs by high-throughput sequencing, and explored their roles with bioinformatics analysis and cell assay to discover more potential pathogenesis about PAH. Our data identified that a total of 559 lncRNAs and 691 mRNAs were differentially expressed in lungs during the pathogenesis of PAH. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses demonstrated that these dysregulated lncRNAs and mRNAs participated in important biological processes and pathways of PAH, among which inflammatory and immune responses represented the chief enriched pathway. The lncRNA-mRNA co-expression network was developed to uncover the hidden interactions between lncRNAs and mRNAs. Further, the expression levels of lncRNAs (NONRATT018084.2, NONRATT009275.2, NONRATT007865.2, and NONRATT026300.2) and mRNAs (LGALS3, PDGFC, SERPINA1, and NFIL3) were confirmed using quantitative real-time PCR. In the end, lncRNA NONRATT009275.2 could facilitate macrophage polarization to M2 type and be involved in inflammatory immune response. In conclusion, this study provided candidate drug targets and potential roles on lncRNAs in the pathogenesis of PAH, and several key regulatory genes were identified, which laid the initial foundation for further mechanism study in PAH.
Are Static and Dynamic Postural Balance Assessments Two Sides of the Same Coin? A Cross-Sectional Study in the Older Adults
Authors: Rizzato Alex , Paoli Antonio , Andretta Marta , Vidorin Francesca , Marcolin Giuseppe
Published: June 2021

The aim of this study was to investigate if the combination of static and dynamic postural balance assessments gives more accurate indications on balance performance among healthy older adults. We also aimed at studying the effect of a dual-task condition on static and dynamic postural balance control. Fifty-seven healthy older adults (age = 73.2 ± 5.0 year, height = 1.66 ± 0.08 m, and body mass = 72.8 ± 13.8 kg) completed the study. Static and dynamic balance were assessed both in single-task and dual-task conditions through a force plate and an oscillating platform. The dominant handgrip strength was also measured with a dynamometer. Pearson’s correlation revealed non-statistically significant correlations between static and dynamic balance performance. The dual-task worsened the balance performance more in the dynamic (+147.8%) than in the static (+25.10%, +43.45%, and +72.93% for ellipse area, sway path, and AP oscillations, respectively) condition (p < 0.001). A weak correlation was found between dynamic balance performance and handgrip strength both in the single (p < 0.05; r = −0.264) and dual (p < 0.05; r = −0.302) task condition. The absence of correlations between static and dynamic balance performance suggests including both static and dynamic balance tests in the assessment of postural balance alterations among older adults. Since cognitive-interference tasks exacerbated the degradation of the postural control performance, dual-task condition should also be considered in the postural balance assessment.
Grape Leaf Black Rot Detection Based on Super-Resolution Image Enhancement and Deep Learning
Authors: Zhu Jiajun , Cheng Man , Wang Qifan , Yuan Hongbo , Cai Zhenjiang
Published: June 2021

The disease spots on the grape leaves can be detected by using the image processing and deep learning methods. However, the accuracy and efficiency of the detection are still the challenges. The convolutional substrate information is fuzzy, and the detection results are not satisfactory if the disease spot is relatively small. In particular, the detection will be difficult if the number of pixels of the spot is <32 × 32 in the image. In order to effectively address this problem, we present a super-resolution image enhancement and convolutional neural network-based algorithm for the detection of black rot on grape leaves. First, the original image is up-sampled and enhanced with local details using the bilinear interpolation. As a result, the number of pixels in the image increase. Then, the enhanced images are fed into the proposed YOLOv3-SPP network for detection. In the proposed network, the IOU (Intersection Over Union, IOU) in the original YOLOv3 network is replaced with GIOU (Generalized Intersection Over Union, GIOU). In addition, we also add the SPP (Spatial Pyramid Pooling, SPP) module to improve the detection performance of the network. Finally, the official pre-trained weights of YOLOv3 are used for fast convergence. The test set test_pv from the Plant Village and the test set test_orchard from the orchard field were used to evaluate the network performance. The results of test_pv show that the grape leaf black rot is detected by the YOLOv3-SPP with 95.79% detection accuracy and 94.52% detector recall, which is a 5.94% greater in terms of accuracy and 10.67% greater in terms of recall as compared to the original YOLOv3. The results of test_orchard show that the method proposed in this paper can be applied in field environment with 86.69% detection precision and 82.27% detector recall, and the accuracy and recall were improved to 94.05 and 93.26% if the images with the simple background. Therefore, the detection method proposed in this work effectively solves the detection task of small targets and improves the detection effectiveness of the grape leaf black rot.
Dysnumeria in Sign Language: Impaired Construction of the Decimal Structure in Reading Multidigit Numbers in a Deaf ISL Signer
Authors: Friedmann Naama , Haluts Neta , Levy Doron
Published: June 2021

We report on the first in-depth analysis of a specific type of dysnumeria, number-reading deficit, in sign language. The participant, Nomi, is a 45-year-old signer of Israeli Sign Language (ISL). In reading multidigit numbers (reading-then-signing written numbers, the counterpart of reading aloud in spoken language), Nomi made mainly decimal, number-structure errors– reading the correct digits in an incorrect (smaller) decimal class, mainly in longer numbers of 5–6-digits. A unique property of ISL allowed us to rule out the numeric-visual analysis as the source of Nomi's dysnumeria: In ISL, when the multidigit number signifies the number of objects, it is signed with a decimal structure, which is marked morphologically (e.g., 84 → Eight-Tens Four); but a parallel system exists (e.g., for height, age, bus numbers), in which multidigit numbers are signed non-decimally, as a sequence of number-signs (e.g., 84 → Eight, Four). When Nomi read and signed the exact same numbers, but this time non-decimally, she performed significantly better. Additional tests supported the conclusion that her early numeric-visual abilities are intact: she showed flawless detection of differences in length, digit-order, or identity in same-different tasks. Her decimal errors did not result from a number-structure deficit in the phonological-sign output either (no decimal errors in repeating the same numbers, nor in signing multidigit numbers written as Hebrew words). Nomi had similar errors of conversion to the decimal structure in number comprehension (number-size comparison tasks), suggesting that her deficit is in a component shared by reading and comprehension. We also compared Nomi's number reading to her reading and signing of 406 Hebrew words. Nomi's word reading was in the high range of the normal performance of hearing controls and of deaf signers and significantly better than her multidigit number reading, demonstrating a dissociation between number reading, which was impaired, and word reading, which was spared. These results point to a specific type of dysnumeria in the number-frame generation for written multidigit numbers, whereby the conversion from written multidigit numbers to the abstract decimal structure is impaired, affecting both reading and comprehension. The results support abstract, non-verbal decimal structure generation that is shared by reading and comprehension, and also suggest the existence of a non-decimal number-reading route.
Emotion Understanding Correlates With Parental Emotional Expressivity in Chinese Youths With Hearing Loss and Typical Hearing
Authors: Hu Yousong , Dong Shuyang , Guan Fang , Chen Outong , Chen Jun , Xu Shurong
Published: June 2021

This study aimed at examining the differences between Chinese youths with hearing loss (HL) and with typical hearing (TH) in emotion understanding (EU), parental emotional expressivity, and the associations between EU and parental emotional expressivity. The participants were 282 youths with HL (14.58 ± 3.42 years old) and 350 youths with TH (11.69 ± 2.49 years old). EU was measured by four visual-mode tasks, of which two involve language comprehension while the others do not. Parents reported positive and negative emotional expressivity on the Self-Expressiveness in the Family Questionnaire. Covariates were controlled for including socioeconomic status, parent gender, youth gender, age, intelligence, and teacher-reported comprehension difficulties. Results showed that the four EU tasks were more challenging for the youths with HL than for the youths with TH. The interaction effect of the two groups × 4 tasks was not significant, suggesting that the differences between the two groups of youths in EU were generally similar across the four tasks. The parents of the youths with HL did not differ from the parents of the youths with TH in how often they displayed positive and negative emotional expressivity. Multigroup regression analyses revealed that negative emotional expressivity was negatively related to EU in the youths with HL but not in the youths with TH. However, these two regression coefficients were not significantly different. Positive emotional expressivity was not related to EU in either group. In conclusion, this study extends the knowledge about the EU of Chinese youths with HL and emotion-related socialization of the parents of these youths.
Tai Chi Chuan Alters Brain Functional Network Plasticity and Promotes Cognitive Flexibility
Authors: Cui Lei , Tao Sha , Yin Heng-chan , Shen Qi-qi , Wang Yuan , Zhu Li-na , Li Xiu-juan
Published: June 2021

Objective: This study used resting-state functional magnetic resonance imaging to investigate the effects of 8 weeks of Tai Chi Chuan and general aerobic exercise on the topological parameters of brain functional networks, explored the advantages of Tai Chi Chuan for improving functional network plasticity and cognitive flexibility, and examined how changes in topological attributes of brain functional networks relate to cognitive flexibility.

Methods: Thirty-six healthy adults were grouped into Tai Chi Chuan (Bafa Wubu of Tai Chi), general aerobic exercise (brisk walking), and control groups. All of the subjects underwent fMRI and behavioral assessment before and after the exercise intervention.

Results: Tai Chi Chuan exercise significantly enhanced the clustering coefficient and local efficiency compared with general aerobic exercise. Regarding the nodal properties, Tai Chi Chuan significantly enhanced the nodal clustering coefficient of the bilateral olfactory cortex and left thalamus, significantly reduced the nodal clustering coefficient of the left inferior temporal gyrus, significantly improved the nodal efficiency of the right precuneus and bilateral posterior cingulate gyrus, and significantly improved the nodal local efficiency of the left thalamus and right olfactory cortex. Furthermore, the behavioral performance results demonstrated that cognitive flexibility was enhanced by Tai Chi Chuan. The change in the nodal clustering coefficient in the left thalamus induced by Tai Chi Chuan was a significant predictor of cognitive flexibility.

Conclusion: These findings demonstrated that Tai Chi Chuan could promote brain functional specialization. Brain functional specialization enhanced by Tai Chi Chuan exercise was a predictor of greater cognitive flexibility.
Neoliberal Ideology in France: A Qualitative Inquiry
Authors: Girerd Lola , Verniers Catherine , Bonnot Virginie
Published: June 2021

This article adds to the existing literature on neoliberal ideology by investigating its content and contours in a context historically marked by statism. Very few studies in social psychology have looked at how neoliberal ideology transpires out of people's discourses and none have done so in such contexts. Yet, this appears necessary in order to better understand its actual influence and how it interacts with localized norms. Relying on a qualitative analysis of 32 semi-structured interviews and on the existing literature, we identified five central themes of neoliberal ideology in France: State prerogatives, competition, abstraction from institutional and social contexts, the entrepreneurial self and emotional management. Results suggest that the influence of neoliberal ideology transpires in the way people envision competition as something natural and motivating, in the way they distance themselves from their immediate and distant contexts, and in the way they value and engage in self-regulation while pursuing happiness and self-optimization. We also found that, in the French context, neoliberal ideology was not necessarily associated to the willingness to see the State step back and to the rationalization of all types of inequalities. Indeed, in the eyes of participants, the State largely remains the guarantor of public services and should ensure an equality of opportunity. This study highlights the value of relying on a qualitative approach to provide a rich and complex account of social realities such as ideologies.