bluuebunny/crossref_metadata_2025_split huggingface dataset:
Budesonide/glycopyrronium/formoterol fumarate triple therapy prevents pulmonary hypertension in a COPD mouse model via NFκB inactivation
Authors: Suraya Ratoe , Nagano Tatsuya , Ryanto Gusty Rizky Teguh , Effendi Wiwin Is , Hazama Daisuke , Katsurada Naoko , Yamamoto Masatsugu , Tachihara Motoko , Emoto Noriaki , Nishimura Yoshihiro , Kobayashi Kazuyuki 
Published: June 2022

Abstract
Background
Chronic obstructive pulmonary disease (COPD) is a health problem that results in death, commonly due to the development of pulmonary hypertension (PH). Here, by utilizing a mouse model of intratracheal elastase-induced emphysema that presents three different phases of COPD, we sought to observe whether budesonide/glycopyrronium/formoterol fumarate (BGF) triple therapy could prevent COPD-PH in addition to ameliorating COPD progression.

Methods
We utilized intratracheal elastase-induced emphysema mouse model and performed experiments in three phases illustrating COPD progression: inflammatory (1 day post-elastase), emphysema (3 weeks post-elastase) and PH (4 weeks post-elastase), while treatments of BGF and controls (vehicle, one-drug, and two-drug combinations) were started in prior to elastase instillation (inflammatory phase), at day 7 (emphysema), or at day 14 (PH phase). Phenotype analyses were performed in each phase. In vitro, A549 cells or isolated mouse lung endothelial cells (MLEC) were treated with TNFα with/without BGF treatment to analyze NFκB signaling and cytokine expression changes.

Results
We observed significant reductions in the proinflammatory phenotype observed in the lungs and bronchoalveolar lavage fluid (BALF) 1 day after elastase administration in mice treated with BGF compared with that in mice administered elastase alone (BALF neutrophil percentage, p = 0.0011 for PBS/Vehicle vs. PBS/Elastase, p = 0.0161 for PBS/Elastase vs. BGF). In contrast, only BGF treatment significantly ameliorated the elastase-induced emphysematous lung structure and desaturation after three weeks of elastase instillation (mean linear intercept, p = 0.0156 for PBS/Vehicle vs. PBS/Elastase, p = 0.0274 for PBS/Elastase vs. BGF). Furthermore, BGF treatment prevented COPD-PH development, as shown by improvements in the hemodynamic and histological phenotypes four weeks after elastase treatment (right ventricular systolic pressure, p = 0.0062 for PBS/Vehicle vs. PBS/Elastase, p = 0.027 for PBS/Elastase vs. BGF). Molecularly, BGF acts by inhibiting NFκB-p65 phosphorylation and subsequently decreasing the mRNA expression of proinflammatory cytokines in both alveolar epithelial and pulmonary endothelial cells.

Conclusion
Our results collectively showed that BGF treatment could prevent PH in addition to ameliorating COPD progression via the inhibition of inflammatory NFκB signaling.
Enhanced extracellular raw starch-degrading α-amylase production in Bacillus subtilis by promoter engineering and translation initiation efficiency optimization
Authors: Li He , Yao Dongbang , Pan Yan , Chen Xin , Fang Zemin , Xiao Yazhong 
Published: June 2022

Abstract
Background
A raw starch-degrading α-amylase from Pontibacillus sp. ZY (AmyZ1), previously screened by our laboratory, showed a promising application potential for starch-processing industries. However, the AmyZ1 secretory production still under investigation, which seriously restricts its application in the starch-processing industry. On the other hand, Bacillus subtilis is widely used to achieve the extracellular expression of target proteins.

Results
AmyZ1 secretory production was achieved in B. subtilis and was enhanced by promoter engineering and translation initiation efficiency optimization. First, based on the different phase-dependent promoters, the dual-promoter PspoVG–PspoVG142 was constructed by combining dual-promoter engineering and promoter modification. The corresponding strain BZd34 showed an extracellular AmyZ1 activity of 1437.6 U/mL during shake flask cultivation, which was 3.11-fold higher than that of the original strain BZ1 (PgroE). Then, based on translation initiation efficiency optimization, the best strain BZd343 containing optimized 5'-proximal coding sequence (opt3) produced the highest extracellular α-amylase activity of 1691.1 U/mL, which was 3.65-fold higher than that of the strain BZ1. Finally, cultivation of BZd343 in 3-L fermenter exhibited an extracellular AmyZ1 activity of 14,012 U/mL at 48 h, with productivity of 291.9 U/mL·h.

Conclusions
This is the first report of recombinant expression of AmyZ1 in B. subtilis and the expression level of AmyZ1 represents the highest raw starch-degrading α-amylase level in B. subtilis to date. The high-level expression of AmyZ1 in this work provides a foundation for its industrial production. The strategies used in this study also provide a strategic reference for improving the secretory expression of other enzymes in B. subtilis.
In vivo experimental validation of detection of gastric slow waves using a flexible multichannel electrogastrography sensor linear array
Authors: Sukasem Atchariya , Calder Stefan , Angeli-Gordon Timothy R. , Andrews Christopher N. , O’Grady Gregory , Gharibans Armen , Du Peng 
Published: June 2022

Abstract
Background
Cutaneous electrogastrography (EGG) is a non-invasive technique that detects gastric bioelectrical slow waves, which in part govern the motility of the stomach. Changes in gastric slow waves have been associated with a number of functional gastric disorders, but to date accurate detection from the body-surface has been limited due to the low signal-to-noise ratio. The main aim of this study was to develop a flexible active-electrode EGG array. Methods: Two Texas Instruments CMOS operational amplifiers: OPA2325 and TLC272BID, were benchtop tested and embedded in a flexible linear array of EGG electrodes, which contained four recording electrodes at 20-mm intervals. The cutaneous EGG arrays were validated in ten weaner pigs using simultaneous body-surface and serosal recordings, using the Cyton biosensing board and ActiveTwo acquisition systems. The serosal recordings were taken using a passive electrode array via surgical access to the stomach. Signals were filtered and compared in terms of frequency, amplitude, and phase-shift based on the classification of propagation direction from the serosal recordings. Results: The data were compared over 709 cycles of slow waves, with both active cutaneous EGG arrays demonstrating comparable performance. There was an agreement between frequencies of the cutaneous EGG and serosal recordings (3.01 ± 0.03 vs 3.03 ± 0.05 cycles per minute; p = 0.75). The cutaneous EGG also demonstrated a reduction in amplitude during abnormal propagation of gastric slow waves (310 ± 50 µV vs 277 ± 9 µV; p < 0.01), while no change in phase-shift was observed (1.28 ± 0.09 s vs 1.40 ± 0.10 s; p = 0.36). Conclusion: A sparse linear cutaneous EGG array was capable of reliably detecting abnormalities of gastric slow waves. For more accurate characterization of gastric slow waves, a two-dimensional body-surface array will be required.
Interleukin-6 and YKL-40 predicted recurrent stroke after ischemic stroke or TIA: analysis of 6 inflammation biomarkers in a prospective cohort study
Authors: Li Jiejie , Lin Jinxi , Pan Yuesong , Wang Mengxing , Meng Xia , Li Hao , Wang Yilong , Zhao Xingquan , Qin Haiqiang , Liu Liping , Wang Yongjun ,   the CNSR-III Investigators
Published: June 2022

Abstract
Objective
Contribution of individual and combined inflammatory markers in prognosis after stroke was still undefined. We aimed to investigate the association of systemic and local vascular inflammatory markers and recurrent stroke as well as impact on poor functional outcome.

Methods
In this pre-specified substudy of the Third China National Stroke Registry (CNSR-III), 10,472 consecutive acute ischemic stroke or TIA patients with available centralized-measured levels of Interleukin-6 (IL-6), high sensitive C-reactive protein (hsCRP), IL-1 receptor antagonist (IL-1Ra), lipoprotein-associated phospholipase A2 mass (Lp-PLA2) and activity (Lp-PLA2-A), and YKL-40 from 171 sites were enrolled. The primary outcomes consisted of stroke recurrence and poor functional outcome defined as modified Rankin Scale (mRS) score of 2–6 within 1 year.

Results
There were 1026 (9.8%) and 2395 (23.4%) patients with recurrent stroke and poor functional outcome within 1 year. The highest quartiles of IL-6 (adjusted HR, 1.36; 95% CI 1.13–1.64; P = 0.001), hsCRP (adjusted HR, 1.41; 95% CI 1.17–1.69; P = 0.0003) and YKL-40 (adjusted HR, 1.28; 95% CI 1.06–1.56; P = 0.01) were associated with increased risk of recurrent stroke; and the highest quartiles of IL-6 (adjusted OR 1.93; 95% CI 1.64–2.27; P < 0.0001), IL-1Ra (adjusted OR 1.60; 95% CI 1.37–1.87; P < 0.0001), hsCRP (adjusted OR 1.60; 95% CI 1.37–1.86; P < 0.0001) and YKL-40 (adjusted OR 1.21; 95% CI 1.03–1.42; P = 0.02) were correlated with increased risk of poor functional outcome. In the multivariate stepwise regression analysis including all markers with backward selection, elevated levels of IL-6 or YKL-40 were associated with recurrent stroke (IL6: OR, 1.34; 95% CI 1.19–1.52; P < 0.0001; YKL-40: OR, 1.01; 95% CI 1.01–1.03; P = 0.004) and poor functional outcome (IL6: OR, 1.68; 95% CI 1.46–1.93; P < 0.0001; YKL-40: OR, 1.02; 95% CI 1.01–1.03; P = 0.0001). Adding IL-6 and YKL-40 significantly increased the area under the receiver operating characteristic curves for the prediction models of Essen Stroke Risk Score (0.03, P < 0.0001) and Totaled Health Risks in Vascular Events Score (0.07, P < 0.0001), and yielded continuous net reclassification improvement (19.0%, P < 0.0001; 33.0, P < 0.0001).

Conclusions
In the patients with ischemic stroke or TIA, IL-6 and YKL-40 were independently associated with recurrent stroke and poor functional outcome, and improved risk classification of clinical risk algorithms.
Prevalence trends and risk factors associated with HIV, syphilis, and hepatitis C virus among pregnant women in Southwest China, 2009–2018
Authors: Zhong Shanmei , Ou Yanyun , Zhang Fei , Lin Zhaosen , Huang Rongye , Nong Aidan , Wu Zhenxian , Liang Huayue , Qin Cai , Wei Qiuyu , Yang Yuan , Yu Dee , Tang Xianyan , Ye Li , Liu Deping , Liang Hao , Liang Bingyu 
Published: June 2022

Abstract
Objective
This study investigated prevalence trends and identified the associated factors of HIV, syphilis and hepatitis C virus (HCV) among pregnant women in the Guangxi Zhuang Autonomous Region (Guangxi), Southwest China.

Methods
Serial cross-sectional surveys were performed annually among pregnant women in Guangxi from 2009 to 2018. Blood specimens were collected to test the prevalence of HIV, syphilis and HCV. Cochran–Armitage analysis was used to assess the trends of HIV, syphilis and HCV prevalence, as well as the sociodemographic and behavioural data. In this study, we used zero-inflated negative binomial (ZINB) regression models to identify factors associated with HIV, syphilis and HCV infection.

Results
A total of 23,879 pregnant women were included in the study. The prevalence of HIV, syphilis and HCV was 0.24%, 0.85% and 0.19%, respectively. There was a decrease in HIV prevalence from 0.54% to 0.10%, a decrease in HCV prevalence from 0.40% to 0.05% and a decrease in syphilis prevalence from 1.53% to 0.30%. The findings based on the ZINB model revealed that pregnant women who had a history of STI had significantly increased risks of HIV (OR 6.63; 95% CI 1.33–32.90) and syphilis (OR 9.06; 95% CI 3.85–21.30) infection, while pregnant women who were unmarried/widowed/divorced were more likely to have HIV (OR 2.81; 95% CI 1.20–6.54) and HCV (OR 58.12; 95% CI, 3.14–1076.99) infection. Furthermore, pregnant women whose husband had a history of STI (OR 5.62; 95% CI 1.24–25.38) or drug use (OR 7.36; 95% CI 1.25–43.43) showed an increased risk of HIV infection.

Conclusions
There was a relatively low prevalence of HIV, syphilis and HCV among pregnant women. Although decreasing trends in HIV, syphilis and HCV infections were observed, effort is needed to promote STI testing in both premarital medical check-ups and antenatal care, especially targeting couples with a history of STI or drug use.
Multi-dimensional impacts of Coronavirus disease 2019 pandemic on Sustainable Development Goal achievement
Authors: Lekagul Angkana , Chattong Anamika , Rueangsom Putthipanya , Waleewong Orratai , Tangcharoensathien Viroj 
Published: June 2022

Abstract
Background
Health, social and economic crises triggered by the Coronavirus disease pandemic (COVID-19) can derail progress and achievement of the Sustainable Development Goals. This commentary analyses the complex nexus of multi-dimensional impacts of the pandemic on people, prosperity, planet, partnership and peace. From our analysis, we generate a causal loop diagram explaining these complex pathways and proposed policy recommendations.

Main text
Health systems, health and wellbeing of people are directly affected by the pandemic, while impacts on prosperity, education, food security and environment are indirect consequences from pandemic containment, notably social measures, business and school closures and international travel restrictions. The magnitude of impacts is determined by the level of prior vulnerability and inequity in the society, and the effectiveness and timeliness of comprehensive pandemic responses.

Conclusions
To exit the acute phase of the pandemic, equitable access to COVID-19 vaccines by all countries and continued high coverage of face masks and hand hygiene are critical entry points. During recovery, governments should strengthen preparedness based on the One Health approach, rebuild resilient health systems and an equitable society, ensure universal health coverage and social protection mechanisms for all. Governments should review progress and challenges from the pandemic and sustain a commitment to implementing the Sustainable Development Goals.
The presence and degradation of nerve fibers in articular cartilage of neonatal rats
Authors: Wang Zheng , Liu Bin , Lin Kaifeng , Duan Chunguang , Wang Chunmei 
Published: June 2022

AbstractPurposeTo investigate the presence and change of nerve fibers and neuropeptide during early development of articular cartilage in neonatal rats.MethodsArticular cartilage in distal-femoral epiphyses was collected from neonatal Sprague Dawley rats, which were 1-day, 5-day, and 10-day postnatal (P1, P5 and P10). Microscopy, immunofluorescence, transmission and scanning electron microscopy (TEM and SEM) were performed for detection of nerve fibers. Quantitative analysis for substance P (SP) and neuropeptide Y (NPY) was conducted using immunofluorescence and enzyme-linked immunosorbent assay (ELISA).ResultsTEM showed the existence of myelinated nerve fibers in the extracellular matrix of articular cartilage in both P1, P5 and P10 rats, and they formed synaptic contacts with chondrocytes. During this time, chondrocytes proceeded with their development, and the nerve fibers gradually degraded. The ELISA results showed significant increase of the sensory neuropeptide SP and the sympathetic neuropeptide NPY in the cartilage tissue. Immunofluorescence results showed the distribution of SP and NPY in the perichondrium, the cartilage canals, the plasma of chondrocytes, and extracellular matrix in the cartilage tissue.ConclusionsNerve fibers exist in the matrix of articular cartilage during early development of knee joints in neonatal rats. Nerve fibers form synaptic contacts with chondrocytes at the early stage and then degrade gradually in the course of chondrocyte development. SP and NPY significantly increase in articular cartilage during this very period. These results indicate that the nerve fibers and the neuropeptide they secrete may exert important effect on the development of articular cartilage.
Association of mast cell density, microvascular density and endothelial area with clinicopathological parameters and prognosis in canine mammary gland carcinomas
Authors: Sakalauskaitė Simona , Riškevičienė Vita , Šengaut Jakov , Juodžiukynienė Nomeda 
Published: June 2022

AbstractBackgroundMast cell density has been shown to have both enhancing and inhibiting effects on tumour progression and the ability to predict breast cancer behaviour in humans. However, prognostic results have been contradictory. Some previous studies suggested involvement of mast cells in the progression of canine mammary tumours. This study investigated total, intratumoural and peritumoural mast cell densities by Giemsa staining, and their association with clinicopathological parameters and the disease outcome of canine mammary tumours. In addition, since mast cells promote angiogenesis, the microvascular density and endothelial area were evaluated by CD31 immunostaining.ResultsIntratumoural mast cell density was associated with tumour size, lymph node involvement and tumour-infiltrating lymphocyte count, while peritumoural mast cell density was associated with grade. The endothelial area was associated with grade, mitotic index, tubular formation and proliferation index. Tumours with a high grade, high total intratumoural mast cell density and a larger endothelial area were associated with shorter disease-free survival. Intratumoural mast cell density and grade were found to be independent prognostic factors.ConclusionsThese results suggest that intratumoural mast cell density and the endothelial area can be used to evaluate the aggressiveness of canine mammary carcinomas, while intratumoural mast cell density could be of use as an independent predictor of a prognosis of disease-free survival. Peritumoural mast cell density does not seem to influence tumour behaviour.
Meeting the 24-h movement guidelines and health-related outcomes among youth with autism spectrum disorder: a seven-country observational study
Authors: Li Chunxiao , Haegele Justin A. , Sun Fenghua , Alves Maria Luiza Tanure , Ang Stefanie Hwee Chee , Lee Jihyun , Ng Kwok , dos Santos Alves Isabella , Healy Sean , Huang Wendy Yajun , Rintala Pauli , Tan Jernice Sing Yee , Wu Yandan , Yang Hannah , Kärnä Eija , Maeng Hyokju , Schliemann André Lisandro , Ding Ding 
Published: June 2022

Abstract
Background
Meeting daily guidelines for physical activity, screen time, and sleep duration is associated with a host of health indicators for youth. In this cross-sectional observational study, we investigated the associations between adherence to the movement guidelines and health-related outcomes among youth with autism spectrum disorder (ASD).

Methods
Parents of youth with ASD (10–17 years) from seven countries and regions were invited to provide online proxy-reports for child’s movement behaviors (i.e., physical activity, sleep and screen time), and health-related outcomes (i.e., body mass index [BMI], general health, and quality of life). A series of multiple linear regression analyses were used to examine the associations between meeting movement guidelines and health-related outcomes, adjusted for covariates.

Results
The final sample consisted of 1165 youth with ASD. Compared with youth meeting all three guidelines, a higher BMI z-score was observed in those who met no guidelines (B = 0.62, P = 0.04), “sedentary time only” (B = 0.60, P = 0.047), and “physical activity plus sleep only” (B = 0.85, P = 0.04). Compared with meeting all three guidelines, meeting no guidelines was associated with poorer general health (B = − 0.46, P = 0.02). Further, compared with youth meeting all three guidelines, a lower quality of life score was observed in those who met no guidelines (B = − 0.47, P = 0.02) and “physical activity only” (B = − 0.62, P = 0.03). Lastly, there were dose–response associations between the number of guidelines met and all three health-related outcomes (all Ptrend < 0.05).

Conclusions
In conclusion, meeting more 24-h movement guidelines was generally associated with more favorable health-related outcomes in youth with ASD. The low level of adherence to all three guidelines (2.0%) suggests the urgent need to promote the adoption of all the guidelines in this group.
Removal of the cervical collar from alpine rescue protocols? A biomechanical non-inferiority trial in real-life mountain conditions
Authors: Grenier Guillaume , Despatis Marc-Antoine , Lebel Karina , Hamel Mathieu , Martin Camille , Boissy Patrick 
Published: June 2022

Abstract
Background
Alpine skiing rescues are challenging because of the mountainous environment and risks of cervical spine motion (CSM) induced during victims’ extrications (EXs) and downhill evacuations (DEs). The benefits of applying a cervical collar (CC) over manual in-line stabilization without CC (MILS) in terms of spinal motion restriction during simulated alpine rescues are undocumented. Our hypothesis was that CSM recorded using MILS alone is non-inferior to CSM recorded with a CC according to a 10 degrees margin.

Methods
A total of 32 alpine extrications and 4 downhill evacuations on different slope conditions were performed using a high fidelity mannequin designed with a motion sensors instrumented cervical spine. The primary outcome was the peak extrication 3D excursion angle (Peak 3D θEX,) of the mannequin’s head. The secondary objectives were to describe the time to extrication completion (tEX) and to highlight which extrication manipulation is more likely to induce CSM.

Results
The median Peak 3D θEX recorded during flat terrain extrications using CC was 10.77° (95% CI 7.31°–16.45°) compared to 13.06° (95% CI 10.20°–30.36°) using MILS, and 16.09° (95% CI 9.07°–37.43°) for CC versus 16.65° (95% CI 13.80°–23.40°) using MILS on a steep slope. Peak 3D θEX with CC or using MILS during extrications were equivalent according to a 10 degrees non-inferiority hypothesis testing (p < 0.05). Time to extrication completion (tEX) was significantly reduced using MILS without CC on a flat terrain with a median duration of 237,3 s (95% CI 197.8 s, 272.2 s) compared to 358.7 s (95% CI 324.1 s, 472.4 s). During downhill evacuations, CSM with and without CC across all terrain conditions were negligible (< 5°). When CC is used; its installation manipulation induces the highest CSM. When EXs are done using MILS without CC, the logroll initiation is the manipulation inducing the highest risk of CSM.

Conclusion
For experienced ski patrollers, the biomechanical benefits of spinal motion restriction provided by CC over MILS during alpine skiing rescues appear to be marginal and CC use negatively affects rescue time.
A theory-based practical solution to correct for sex-differential participation bias
Authors: Lee Hanbin , Han Buhm 
Published: June 2022

AbstractMost genomic cohorts are retrospective where the exposures and outcomes are predetermined prior to sample collection. Therefore, a spurious association between an exposure and an outcome can arise if both variables affect study participation. Such concerns were raised in previous studies questioning the representativeness of the UK Biobank. Recently, a genome-wide association study (GWAS) on biological sex found many autosomal hits and non-negligible autosomal heritability which the authors attribute to selection bias. In this study, we propose a simple and a practical method that can overcome sex-driven selection bias based on theoretical analysis and simulations.