bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial distribution and tectonic significance of the landslides triggered by the 2021 Ms6.4 Yangbi earthquake, Yunnan, China
Authors: He Xiangli , Xu Chong
Published: October 2022

An Ms6.4 earthquake occurred on 21 May 2021 in Yangbi County, Yunnan Province, located in the strong earthquake hazard zone, the border of the Sichuan-Yunnan rhomb block, southeast Tibetan Plateau, causing severe loss of life and property. Adequate research on the distribution characteristics and seismotectonic mechanisms of seismic chain-generated hazards in the region is meaningful for mitigating seismic hazard risks. In this paper, based on the interpretation of remote sensing satellite images and the analysis on GeoScene platform, we compile a detailed inventory of landslides induced by the Yangbi earthquake and analyze the correlation of their spatial distribution with the influence factors. The results show that 95 landslides were interpreted, and their spatial distribution is correlated to the topographic, seismic and geological factors. Statistically, the landslide number and mobility increase with the slope angle; the south- and southeast-facing slopes and weaker metamorphic rocks are more prone to landslides; the higher the seismic intensity, the larger the density and scale of landslides. Furthermore, the development of the landslides is not only influenced by the Ms6.4 mainshock, but also by the Ms5.6 foreshock, which is significantly correlated with the size of landslides. Notably, the long axis of the landslide distribution area is in NW-SE direction, which is nearly parallel to the strike of the Weixi-Qiaohou-Weishan fault zone (WQWF). The landslides are mainly distributed in the southwest wall and southeast section of the fault. The landslide number and density unstably decrease with the vertical distance from the fault with many fluctuations. Combined with the previous studies, two possible seismogenic structure models are inferred. One model is a parallel secondary fault of the WQWF, Another one is a flower structure in the southwest wall of the WQWF. Both models are mainly characterized by right-lateral strike slip with a small normal-fault component. Additionally, the seismic rupture propagated mainly to the southeast along the seismogenic fault in the subsurface without surface rupture.
Should spirituality be included in entrepreneurship education program curriculum to boost students’ entrepreneurial intention?
Authors: Hadi Sutarto , Abbas Ersis Warmansyah , Rajiani Ismi
Published: October 2022

Spirituality is now becoming popular because of the physical and mental advantages it brings to entrepreneurship. Regardless of its more philosophical measurement, changes owing to spirituality have been distinguished in people’s mental and standards of conduct. This investigation aims to examine the qualities related to university students, looking to explicitly comprehend the separate individual qualities or the psychological and cognitive inclinations. Tested on a sample of 300 students, Structural Equation Modeling results exhibit that those who participate in spiritual rituals tend to reinforce the mental and psychological credits connected with an entrepreneurial intention. Since entrepreneurial behavior is a priority to boost economic growth, spirituality should be coordinated as a mandatory subject in general instruction from primary school onward. The results of this exploration could be a model for the Indonesian government as they attempt to search for the best model for Entrepreneurship Education Program (EEP).
Prolactin is associated with bone mineral density in subjects with type 2 diabetes mellitus
Authors: Chen Jia , Liu Geng , Li Quan , Deng Wei
Published: October 2022

Purpose

Prolactin (PRL) exerts actions in the bone besides lactation and reproduction. This study aimed to investigate whether PRL is related to bone mineral density (BMD) in type 2 diabetes mellitus (T2DM).

Methods

A total of 642 patients with T2DM were divided into two groups with age and body mass index (BMI) matched: mildly increased PRL (HP group, n = 101) or normal PRL (NP group, n = 541). BMD was measured by dual-energy X-ray absorptiometry and compared.

Results

1) BMD, T score at lumbar spine L1–4, right hip and femur neck, and Z score at the femur neck were significantly higher in the HP than in the NP group (0.96 ± 0.16 vs. 0.92 ± 0.15g/cm2, p = 0.019; 0.88 ± 0.15vs. 0.84 ± 0.14 g/cm2, p = 0.007; 0.75 ± 0.17 vs.0.70 ± 0.13 g/cm2, p = 0.001; -0.90 (-1.85, -0.20) vs. -1.40 (-2.20, -0.40), p = 0.018; -0.80 (-1.50, -0.30) vs. -1.10 (-1.80, -0.53), p = 0.026; -1.30 (-2.00, -0.60) vs. -1.70 (-2.20, -1.00), p = 0.001; -0.20 (-0.70, 0.30) vs. -0.40 (-0.90, 0.10), p = 0.026). In men, T and Z scores at the right hip and femur neck were significantly higher in the HP than in the NP group (-0.70 (-1.32, 0.20) vs. -0.90 (-1.50, -0.40), p = 0.038; -0.20 (-0.80, 0.20) vs. -0.50 (-0.10, 0.10), p = 0.027; -0.30 (-0.60, -0.30) vs. -0.40 (-0.90, 0.20), p = 0.038) but not in women. Bone turnover markers have no significant difference between groups (all p > 0.05). 2) BMD at the right hip and Z score at the right hip and femur neck were significantly positively associated with PRL (r = 0.087, p = 0.029; r = 0.089, p = 0.024; r = 0.087, p = 0.029). In men, BMD at L1–4 and the right hip; T score at L1–4, the right hip, and the femur neck; and Z score at the right hip and the femur neck were significantly positively associated with PRL (r = 0.122, p = 0.007; r = 0.105, p = 0.041; r = 0.123, p = 0.016; r = 0.110, p = 0.032; r = 0.115, p = 0.025; r = 0.121, p = 0.018; r = 0.138, p = 0.007) but not significant in women. 3) In men divided into two groups according to T score (T score at the right hip>-1 or T score at the right hip≤-1) or the median BMD at L1–4, the right hip or the femur neck, PRL was significantly higher in the higher BMD than in the lower BMD group (16.32 ± 6.12 vs. 14.78 ± 5.68 ng/ml, p = 0.012; 16.20 ± 6.21 vs. 14.73 ± 5.40 ng/ml, p = 0.014; 16.10 ± 6.01 vs. 14.80 ± 5.77 ng/ml, p = 0.032; 16.17 ± 6.04 vs. 14.76 ± 5.77 ng/ml, p = 0.02; 16.48 ± 6.05 vs. 14.98 ± 5.81 ng/ml, p = 0.020; 16.10 ± 5.98 vs. 14.80 ± 5.87 ng/ml, p = 0.035).

Conclusion

Increased PRL was associated with better BMD in patients with T2DM, especially in men. PRL within the biologically normal range may play a protective role in the BMD of T2DM.
Benign thyroid disease and the risk of breast cancer: An updated systematic review and meta-analysis
Authors: Han Mingyue , Wang Yao , Jin Yuanhui , Zhao Xue , Cui Haiying , Wang Guixia , Gang Xiaokun
Published: October 2022

Background

The correlation between benign thyroid disease (BTD) and breast cancer (BC) has long been discussed. However, the definite relationship and potential mechanism between them are still disputed. The current meta-analysis aimed at performing a comprehensive assessment of the relationship between different types of benign thyroid disease and the risk of breast cancer, furthermore, assessing whether benign thyroid disease exerts an influence on the aggressiveness of breast cancer.

Method

A systematic literature search (PubMed, Web of Science, MEDLINE, and Embase databases) identified studies to evaluate the correlation between BTD and BC risk. Data were analyzed using version 16.0 STATA software, including the odds ratio (OR) and its corresponding 95% confidence intervals (CIs). Publication bias and quality assessment were conducted for the included studies.

Result

Overall, 18 studies involving 422,384 patients with BTD were incorporated. The outcome showed that autoimmune thyroiditis (OR: 2.56, 95%CI: 1.95–3.37, I2 = 0.0%, p=0.460), goiter (OR: 2.13, 95%CI: 1.19-3.79, I2 = 80.6%, p=0.000), and Graves’ disease (OR: 5.01, 95%CI: 1.49-16.82, I2 = 0.0%, p=0.358) was connected with a higher risk of BC. Both hypothyroidism (OR: 0.82, 95%CI: 0.64-1.04, I2 = 85.0%, p=0.000) and hyperthyroidism (OR: 1.07, 95%CI: 0.93-1.24, I2 = 24.9%, p=0.206) had no significant association with the risk of BC. Additionally, the pooled analysis showed no apparent correlation between BTD and aggressiveness of BC. However, subgroup analysis indicated a positive relationship between BTD and aggressiveness of BC in the Europe subgroup (HR: 2.05, 95%CI: 1.32-3.17, I2 = 86.4%, p=0.000).

Conclusion

Autoimmune thyroiditis, goiter, and Graves’ disease are connected with an increased risk of BC. Furthermore, subgroup analysis suggested that BTD increases the aggressiveness of BC in the European population geographically. Nevertheless, further research is needed to prove these discoveries.
The neuroprotective effect of melatonin in glutamate excitotoxicity of R28 cells and mouse retinal ganglion cells
Authors: Wang Chao , An Yaqiong , Xia Zhaohua , Zhou Xuezhi , Li Haibo , Song Shuang , Ding Lexi , Xia Xiaobo
Published: October 2022

Glaucoma is the leading cause of irreversible blindness. The progressive degeneration of retinal ganglion cells (RGCs) is the major characteristic of glaucoma. Even though the control of intraocular pressure could delay the loss of RGCs, current clinical treatments cannot protect them directly. The overactivation of N-methyl-D-aspartic acid (NMDA) receptors by excess glutamate (Glu) is among the important mechanisms of RGC death in glaucoma progression. Melatonin (MT) is an indole neuroendocrine hormone mainly secreted by the pineal gland. This study aimed to investigate the therapeutic effect of MT on glutamate excitotoxicity of mouse RGCs and R28 cells. The Glu-induced R28 cell excitotoxicity model and NMDA-induced retinal injury model were established. MT was applied to R28 cells and the vitreous cavity of mice by intravitreal injection. Cell counting kit-8 assay and propidium iodide/Hoechst were performed to evaluate cell viability. Reactive oxygen species and glutathione synthesis assays were used to detect the oxidative stress state of R28 cells. Retina immunofluorescence and hematoxylin and eosin staining were applied to assess RGC counts and retinal structure. Flash visual-evoked potential was performed to evaluate visual function in mice. RNA sequencing of the retina was performed to explore the underlying mechanisms of MT protection. Our results found that MT treatment could successfully protect R28 cells from Glu excitotoxicity and decrease reactive oxygen species. Also, MT rescued RGCs from NMDA-induced injury and protected visual function in mice. This study enriches the indications of MT in the treatment of glaucoma, providing practical research ideas for its comprehensive prevention and treatment.
A modified deep residual network for short-term load forecasting
Authors: Kondaiah V. Y. , Saravanan B.
Published: October 2022

The electrical load has a prominent position and a very important role in the day-to-day operations of the entire power system. Due to this, many researchers proposed various models for forecasting load. However, these models are having issues with over-fitting and the capability of generalization. In this paper, by adopting state-of-the-art of deep learning, a modified deep residual network (deep-ResNet) is proposed to improve the precision of short-term load forecasting and overcome the above issues. In addition, the concept of statistical correlational analysis is used to identify the appropriate input features extraction ability and generalization capability in order to progress the accuracy of the model. Two utility (ISO-NE and IESO-Canada) datasets are considered for evaluating the proposed model performance. Finally, the prediction results obtained from the proposed model are promising as well as accurate when compared with the other existing models in the literature.
Renewable energy incentives on the road to sustainable development during climate change: A review
Authors: Tryndina Nicole , An Jaehyung , Varyash Igor , Litvishko Oleg , Khomyakova Lyubov , Barykin Sergey , Kalinina Olga
Published: October 2022

This review is dedicated to the analytical literature concerning the dynamics of different approaches to renewable energy promotion. Examples of major types of green energy incentives, including carbon tax, Feed-in Tariffs, and investments in research and development are covered in the paper, as well as the barriers and limitations to such practices and the contradictions existing in the field of renewable energy. The dynamics of the means of green energy promotion over this period have been addressed. This review analyzes energy considerations and the importance of raising public awareness on the issue. The evidence collected through the literature analysis, has proven that despite of a significant amount of work done in the field in the transition to the renewable energy sources, including the implementation of various incentives, controversial aspects remain that demand attention both from economists and policymakers. Modern best practices in the field of green energy incentives can be based on government initiatives or stem from the private sector. The most widely used policies for renewable energy promotion discussed in the reviewed studies are tax incentives; however, at the same time, numerous countries are providing fossil fuels subsidies to minimize the level of inequality. Finally, the outlook of different practices concerning financing of the transition from traditional energy sources to renewable ones is presented.
Effects of winter pulsed warming and snowmelt on soil nitrogen cycling in agricultural soils: A lysimeter study
Authors: Green Danielle , Rezanezhad Fereidoun , Jordan Sean , Wagner-Riddle Claudia , Henry Hugh A. L. , Slowinski Stephanie , Van Cappellen Philippe
Published: October 2022

In cold regions, climate change is expected to result in warmer winter temperatures and increased temperature variability. Coupled with changing precipitation regimes, these changes can decrease soil insulation by reducing snow cover, exposing soils to colder temperatures and more frequent and extensive soil freezing and thawing. Freeze-thaw events can exert an important control over winter soil processes and the cycling of nitrogen (N), with consequences for soil health, nitrous oxide (N2O) emissions, and nearby water quality. These impacts are especially important for agricultural soils and practices in cold regions. We conducted a lysimeter experiment to assess the effects of winter pulsed warming, soil texture, and snow cover on N cycling in agricultural soils. We monitored the subsurface soil temperature, moisture, and porewater geochemistry together with air temperature, precipitation, and N2O fluxes in four agricultural field-controlled lysimeter systems (surface area of 1 m2 and depth of 1.5 m) at the University of Guelph’s Elora Research Station over one winter (December 2020 to April 2021). The lysimeters featured two soil types (loamy sand and silt loam) which were managed under a corn-soybean-wheat rotation with cover crops. Additionally, ceramic infrared heaters located above two of the lysimeters were turned on after each snowfall event to melt the snow and then turned off to mimic snow-free winter conditions with increased soil freezing. Porewater samples collected from five depths in the lysimeters were analyzed for total dissolved nitrogen (TDN), nitrate (NO3−), nitrite (NO2−), and ammonium (NH4+). N2O fluxes were measured using automated soil gas chambers installed on each lysimeter. The results from the snow removed lysimeters were compared to those of lysimeters without heaters (with snow). As expected, the removal of the insulating snow cover resulted in more intense soil freeze-thaw events, causing increased dissolved N loss from the lysimeter systems as N2O (from the silt loam system) and via NO3− leaching (from the loamy sand system). In the silt loam lysimeter, we attribute the freeze thaw-enhanced N2O fluxes to de novo processes rather than gas build up and release. In the loamy sand lysimeter, we attribute the increased NO3− leaching to the larger pore size and therefore lower water retention capacity of this soil type. Overall, our study illustrates the important role of winter snow cover dynamics and soil freezing in modulating the coupled responses of soil moisture, temperature, and N cycling.
Lessons from project-scale reducing emissions from deforestation and forest degradation: A case study in northern Lao People’s Democratic Republic
Authors: Hiratsuka Motoshi , Hashiguchi Hozumi , Toda Miki , Yamanoshita Makino Yamada
Published: October 2022

The reducing emissions from deforestation and forest degradation (REDD+) framework has been implemented over the past decade, and has led to a restructuring of forest governance systems in host countries. In the case of Lao People’s Democratic Republic, which is promoting REDD+, activities have been implemented at project, sub-national, and national scales. Project-scale REDD+ is assumed to be compatible with small-scale forestry, and usually targets local people to enhance participatory forest management through technology transfer. Such projects were also supported by foreign governments under bilateral cooperation or by private funding. In the case of sub-national- or national-scale REDD+, the Lao People’s Democratic Republic government aims to develop a system of forest monitoring, as well as related structures required by international REDD+ entities. These activities are supported by substantial funding from multilateral organizations. Lessons learned from project-scale REDD+ in northern Lao People’s Democratic Republic showed a gap in expectations among different donors and recipients regarding how to implement REDD+, in particular how to reduce dependency on forest resources in rural areas, and how to estimate and account for greenhouse gas emissions reductions with consistent methodologies at different scales. Such differences are related to the attitudes of local people toward participation, and those of the private entities that fund projects and ground-based activities. In future REDD+ schemes, the structural network or structural social capital among project-, sub- national-, and national-scale activities should be reconsidered to enhance the continued participation of stakeholders and make use of their accumulated experience and knowledge of small-scale forestry management.
The role of a cuproptosis-related prognostic signature in colon cancer tumor microenvironment and immune responses
Authors: Xu Chenyang , Liu Yonghao , Zhang Yuxi , Gao Ling
Published: October 2022

Background: Colon adenocarcinoma (COAD) is a common malignant tumor of the digestive tract with poor clinical outcomes. Cuproptosis is a novel cell death mechanism and linked to mitochondrial respiration. However, the role of cuproptosis in colon cancer tumor microenvironment (TME) and immune responses remains unknown.

Methods: We conducted difference analysis to identify the differential expressed cuproptosis-related genes (CRGs). According to the CRGs, the TCGA-COAD samples were categorized using consensus clustering. The LASSO regression analysis was utilized to develop the cuproptosis-related signature. We then verified the model reliability by Kaplan–Meier, PCA, and ROC analysis. The GES39582 cohort served as the validation set. GO and KEGG functional analyses were conducted to investigate the underlying mechanism. We compared the infiltration levels of immune cells, the expression levels of immune checkpoints, and microsatellite instability (MSI) status between the high- and low-risk groups. Additionally, the relationships between the risk signature and immune cells and cancer stem cell (CSC) were analyzed.

Results: Finally, we identified 9 differentially expressed CRGs in COAD. According to the expression of CRGs, the TCGA-COAD samples were separated into two clusters. The 11-gene signature was established by LASSO, and it had excellent predictive power for COAD prognosis. Besides, we used the GSE39582 cohort to validate the prognostic value of the model. GO and KEGG results demonstrated that the survival differences between two risk groups was mainly linked to the extracellular matrix (ECM). Further immune characterization analysis showed the significant differences in the immune cell infiltration and immune responses between two risk groups.

Conclusion: Overall, the novel cuproptosis-related signature was able to accurately predict COAD prognosis and played important roles in COAD tumor microenvironment and immune responses.
Genomic insights into the genetic structure and population history of Mongolians in Liaoning Province
Authors: Hou Xuwei , Zhang Xianpeng , Li Xin , Huang Ting , Li Wenhui , Zhang Hailong , Huang He , Wen Youfeng
Published: October 2022

The Mongolian population exceeds six million and is the largest population among the Mongolic speakers in China. However, the genetic structure and admixture history of the Mongolians are still unclear due to the limited number of samples and lower coverage of single-nucleotide polymorphism (SNP). In this study, we genotyped genome-wide data of over 700,000 SNPs in 38 Mongolian individuals from Fuxin in Liaoning Province to explore the genetic structure and population history based on typical and advanced population genetic analysis methods [principal component analysis (PCA), admixture, FST, f3-statistics, f4-statistics, qpAdm/qpWave, qpGraph, ALDER, and TreeMix]. We found that Fuxin Mongolians had a close genetic relationship with Han people, northern Mongolians, other Mongolic speakers, and Tungusic speakers in East Asia. Also, we found that Neolithic millet farmers in the Yellow River Basin and West Liao River Basin and Neolithic hunter–gatherers in the Mongolian Plateau and Amur River Basin were the dominant ancestral sources, and there were additional gene flows related to Eurasian Steppe pastoralists and Neolithic Iranian farmers in the gene pool of Fuxin Mongolians. These results shed light on dynamic demographic history, complex population admixture, and multiple sources of genetic diversity in Fuxin Mongolians.
The emerging role of histone deacetylase 1 in allergic diseases
Authors: Wang Yongfang , Wang Huiying
Published: October 2022

Histone deacetylase 1 (HDAC1) is a unique member of the classes I HDACs and helps to regulate acute and chronic adaptation to environmental stimuli such as allergen, stress. Allergic diseases are complex diseases resulting from the effect of multiple genetic and interacting foreign substances. Epigenetics play an important role in both pathological and immunomodulatory conditions of allergic diseases. To be consistent with this role, recent evidence strongly suggests that histone deacetylase 1 (HDAC1) plays a critical role in allergic response. HDAC1 expression is stimulated by allergen and attributes to increase T helper 2 (Th2) cytokine levels, decrease Th1/Th17 cells and anti-inflammatory cytokine Interleukin-10 (IL-10), and TWIK-related potassium channel-1 (Trek-1) expression. This review focuses on the contribution of HDAC1 and the regulatory role in characterizing allergic endotypes with common molecular pathways and understanding allergic multimorbidity relationships, as well as addressing their potential as therapeutic targets for these conditions.
In-situ long-period monitoring of suspended particulate matter dynamics in deep sea with digital video images
Authors: Wang Hui , Hu Cong , Feng Xuezhi , Ji Chunsheng , Jia Yonggang
Published: October 2022

Suspended particulate matter (SPM) plays an important role in material transport, deposition, resuspension and the function of benthic communities’ processes in deep sea. SPM concentration data is usually indirectly measured by optical/acoustic sensors. However, converting these sensors’ signal to SPM concentration is associated with a number of uncertainties, which will lead to mis-estimation of the results. Some researchers recommend combining several optical/acoustic sensors to determine SPM concentration. However, due to the lack of corresponding video images, the interpretation of significant mismatch signals recorded by different sensors is subjective. Consequently, a better understanding of long-period SPM dynamics, especially in deep sea, is still a challenge. In this study, we seek to monitor the dynamics of SPM in deep sea, by firstly obtaining in-situ digital video images at a water depth of 1450 m on the northern slope of South China Sea in 2020, and secondly developing a digital image processing method to process the in-situ monitoring data. In this method, we defined an image signal which was the ratio between the area of the SPM and that of the total image, to characterize the SPM concentration. A linear regression model of the image signal and SPM concentration was established (R2 = 0.72). K-fold cross-validation showed that the performance of the model was well. We calculated the SPM concentration derived from image signal, and manually classified SPM into three distinct morphological groups. The long-period observation revealed that numerous aggregates existed in deep sea. The change of SPM concentration and morphology under hydrodynamics was synchronous. When current speed equaled to or exceeded 0.15 m/s, there was a significantly increase in SPM concentration and size. However, such increase was episodic. When current speed decreased, they will also decrease. In addition, we compared the image signal with the optical/acoustic backscattering signal, analyzed the mismatch period among these three signals. We found that the optical backscatter signal can’t accurately reflect the SPM concentration during the mismatch period. To our best knowledge, this is the first time that the in-situ digital video images were used to analyze the dynamics of SPM in deep sea.
A brief review of variable stiffness and damping magnetorheological fluid dampers
Authors: Deng Huaxia , Lian Xinyu , Gong Xinglong
Published: October 2022

With the development of magnetorheological fluid (MRF) technology, variable stiffness and damping MRF dampers as semi-active controllers gradually show their unique advantages in the vibration control field. This paper reviews recent journal articles on the principles, characteristics, structure design, modelling and applications of variable stiffness and damping MRF dampers. The principle includes the force behaviour of the MRF fluid and the mechanism of the variable stiffness and damping MRF damper. Characteristics introduce the damper’s force-displacement relationships, which have frequency dependence and amplitude dependence. Following this, typical dampers structures are discussed, including electromagnetic design and coil configuration. After that, some common models and parameter optimization methods are presented. Furthermore, taking vehicle suspension as an example, the applications of variable stiffness and damping MRF dampers in some fields are proposed in this paper.
Can nirmatrelvir/ritonavir treatment shorten the duration of COVID-19 isolation?
Authors: Kim Haein , Yang Jeong-Sun , Ko Jae-Hoon , Lee Myungsun , Lee Joo-Yeon , Park Sehee , Kim Jun-Won , Shin Younmin , Lee Jung-Min , Na Yoo Jin , Park Byoung Kwon , Kim Hyungjin , Lee Young Ho , Yang Jinyoung , Huh Kyungmin , Cho Sun Young , Kang Cheol-In , Chung Doo Ryeon , Peck Kyong Ran
Published: October 2022

Background

The impact of nirmatrelvir/ritonavir treatment on shedding of viable virus in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear.

Methods

A prospective cohort study evaluating mildly ill COVID-19 patients was conducted. Virologic responses were compared between nirmatrelvir/ritonavir-treatment and supportive care groups. Risk factors and relevant clinical factors for shedding of viable virus were investigated.

Results

A total of 80 COVID-19 patients were enrolled and 222 sputum specimens were collected. Ten patients were dropped during follow-up, and 33 patients in the nirmatrelvir/ritonavir and 37 in the supportive care groups were compared. The median age was 67 years, and 67% were male. Clinical characteristics were similar between groups. Viral loads decreased significantly faster in the nirmatrelvir/ritonavir group compared with the supportive care group (P < 0.001), and the slope was significantly steeper (–2.99 ± 1.54 vs. –1.44 ± 1.52; P < 0.001). The duration of viable virus shedding was not statistically different between groups. In the multivariable analyses evaluating all collected specimens, male gender (OR 2.51, 95% CI 1.25–5.03, P = 0.010), symptom score (OR 1.41, 95% CI 1.07–1.87, P = 0.015), days from symptom onset (OR 0.72, 95% CI 0.59–0.88, P = 0.002), complete vaccination (OR 0.09, 95% CI 0.01–0.87, P = 0.038), and BA.2 subtype (OR 0.49, 95% CI 0.26–0.91, P = 0.025) were independently associated with viable viral shedding, while nirmatrelvir/ritonavir treatment was not.

Conclusion

Nirmatrelvir/ritonavir treatment effectively reduced viral loads of SARS-CoV-2 Omicron variants but did not decrease the duration of viable virus shedding.
Sarcoidosis: Updates on therapeutic drug trials and novel treatment approaches
Authors: Obi Ogugua Ndili , Saketkoo Lesley Ann , Russell Anne-Marie , Baughman Robert P.
Published: October 2022

Sarcoidosis is a systemic granulomatous inflammatory disease of unknown etiology. It affects the lungs in over 90% of patients yet extra-pulmonary and multi-organ involvement is common. Spontaneous remission of disease occurs commonly, nonetheless, over 50% of patients will require treatment and up to 30% of patients will develop a chronic progressive non-remitting disease with marked pulmonary fibrosis leading to significant morbidity and death. Guidelines outlining an immunosuppressive treatment approach to sarcoidosis were recently published, however, the strength of evidence behind many of the guideline recommended drugs is weak. None of the drugs currently used for the treatment of sarcoidosis have been rigorously studied and prescription of these drugs is often based on off-label” indications informed by experience with other diseases. Indeed, only two medications [prednisone and repository corticotropin (RCI) injection] currently used in the treatment of sarcoidosis are approved by the United States Food and Drug Administration. This situation results in significant reimbursement challenges especially for the more advanced (and often more effective) drugs that are favored for severe and refractory forms of disease causing an over-reliance on corticosteroids known to be associated with significant dose and duration dependent toxicities. This past decade has seen a renewed interest in developing new drugs and exploring novel therapeutic pathways for the treatment of sarcoidosis. Several of these trials are active randomized controlled trials (RCTs) designed to recruit relatively large numbers of patients with a goal to determine the safety, efficacy, and tolerability of these new molecules and therapeutic approaches. While it is an exciting time, it is also necessary to exercise caution. Resources including research dollars and most importantly, patient populations available for trials are limited and thus necessitate that several of the challenges facing drug trials and drug development in sarcoidosis are addressed. This will ensure that currently available resources are judiciously utilized. Our paper reviews the ongoing and anticipated drug trials in sarcoidosis and addresses the challenges facing these and future trials. We also review several recently completed trials and draw lessons that should be applied in future.
Assessment of 99mTc-NTP 15-5 uptake on cartilage, a new proteoglycan tracer: Study protocol for a phase I trial (CARSPECT)
Authors: Thivat Emilie , Chanchou Marion , Mathieu Sylvain , Levesque Sophie , Billoux Tommy , Auzeloux Philippe , Sas Nicolas , Molnar Ioana , Jouberton Elodie , Rouanet Jacques , Fois Giovanna , Maigne Lydia , Galmier Marie-Josephe , Penault-Llorca Frédérique , Miot-Noirault Elisabeth , Durando Xavier , Cachin Florent
Published: October 2022

Background

99mTc-NTP 15-5 is a SPECT radiotracer targeting proteoglycans (PG), components of the cartilaginous extracellular matrix. Imaging of PGs would be useful for the early detection of cartilage disorders (osteoarthritis, arthritis and chondrosarcoma, Aromatase Inhibitor associated arthralgia (AIA) in breast cancer), and the follow-up of patients under treatment. According to preclinical study results, 99mTc-NTP 15-5, is a good candidate for a specific functional molecular imaging of joints. We intend to initiate a first in-human study to confirm and quantify 99mTc-NTP 15-5 uptake in healthy joints.

Methods

As the clinical development of this radiotracer would be oriented toward the functional imaging of joint pathologies, we have chosen to include patients with healthy joints (unilateral osteoarthritis of the knee or breast cancer with indication of AI treatment). This phase I study will be an open-label, multicenter, dose-escalation trial of a radiopharmaceutical orientation to determine the recommended level of activity of 99mTc-NTP 15-5 to obtain the best joint tracer contrasts on images, without dose limiting toxicity (DLT). The secondary objectives will include the study of the pharmacology, biodistribution (using planar whole body and SPECT-CT acquisitions), toxicity, and dosimetry of this radiotracer. The dose escalation with 3 activity levels (5, 10, and 15 MBq/kg), will be conditioned by the absence at the previous level of DLT and of a visualized tracer accumulation on more than 80% of healthy joints as observed on scintigraphy performed at ≤ 2 h post-injection.

Discussion

This first in-human phase I trial will be proof-of-concept of the relevance of 99mTc-NTP 15-5 as a cartilage tracer, with the determination of the optimal methodology (dose and acquisition time) to obtain the best contrast to provide a functional image of joints with SPECT-CT.

Trial registration number

Clinicaltrials.gov: NCT04481230. Identifier in French National Agency for the Safety of Medicines and Health Products (ANSM): N°EudraCT 2020-000495-37.
Administration of selenomethionine in combination with serine benefits diabetes via gut microbiota
Authors: Cui Xiaoyan , Chen Jingqing , Yang Yuexi
Published: October 2022

Either selenium or serine could modulate glucose homeostasis, however, whether there are synergistic effects of selenium with serine on diabetes remains to be unknown. In the present study, eight male db/m mice were used as a control, and 24 male diabetic db/db mice were either orally gavaged with PBS, or with selenomethionine alone, or with both selenomethionine and serine, to investigate the effects of selenomethionine and serine on body weight and glucose level. Furthermore, intestinal microbiota composition was analyzed and fecal microbiota transplantation (FMT) was performed to explore whether microbes mediate the beneficial effects of selenomethionine and serine. The results showed that administration of selenomethionine decreased body weight, adipose tissue weight and serum glucose level in db/db diabetic mice. Importantly, administration of selenomethionine in combination with serine exerted better effects than selenomethionine alone did. Furthermore, a combined administration of selenomethionine and serine restored the microbial composition in diabetic mice. Corynebacterium glutamicum, Bifidobacterium pseudolongum, and Aerococcus urinaeequi were significantly decreased, whereas Lactobacillus murinus was increased in mice in the selenomethionine group and selenomethionine in combination with serine group, when compared with those in the db/db group. FMT decreased body weight and glucose level in db/db mice, further indicating that microbes play critical roles in the beneficial effects of selenomethionine and serine. Thus, we concluded that administration of selenomethionine in combination with serine benefits diabetes via gut microbes. Our results suggested that the synergic application of selenomethionine and serine could be potentially used for the treatment of diabetes.
Gut microbiota modulation by plant polyphenols in koi carp (Cyprinus carpio L.)
Authors: Zhang Rong , Kang Xin , Liu Lili , Wang Xiaowen , Li Huijuan , Zhu Jianya , Cao Yongchun , Zhu Hua
Published: October 2022

Plant polyphenol supplementation may improve fish health in aquaculture systems. To assess the potential benefits and function mechanism of plant polyphenols in aquaculture, fish were fed either basal feed (CON) or the basal feed supplemented with 500 mg/kg of curcumin (CUR), oligomeric proanthocyanidins (OPC), chlorogenic acid (CGA), or resveratrol (RES). After an 8-week feeding experiment, blood samples were used to analyze the concentrations of biochemical indices. Gut samples were collected to evaluate microbiota, short chain fatty acid (SCFA) levels, and gene expression. The results indicated that polyphenol administration reduced serum glucose and insulin. Lysozyme activity was enhanced by OPC and CGA, and superoxide dismutase activity was increased by CUR, OPC, and CGA. The gut microbial structure of the RES group was segregated from that of the CON, and the genus Bacteroides was identified as a potential biomarker in the CUR, CGA, and RES groups. Total gut SCFA increased in the CUR, CGA, and RES groups. A strong correlation was observed between Bacteroides and SCFA. In conclusion, dietary polyphenols have distinct anti-inflammatory, anti-oxidant, and anti-hyperglycemic activities that may be closely associated with their microbiota-modulation effects.
Epithelial-mesenchymal transition-related long noncoding RNAs in gastric carcinoma
Authors: Feng Ying-Nan , Li Bo-Ya , Wang Ke , Li Xiao-Xi , Zhang Lan , Dong Xian-Zhe
Published: October 2022

As an evolutionarily phenotypic conversion program, the epithelial-mesenchymal transition (EMT) has been implicated in tumour deterioration and has facilitated the metastatic ability of cancer cells via enhancing migration and invasion. Gastric cancer (GC) remains a frequently diagnosed non-skin malignancy globally. Most GC-associated mortality can be attributed to metastasis. Recent studies have shown that EMT-related long non-coding RNAs (lncRNAs) play a critical role in GC progression and GC cell motility. In addition, lncRNAs are associated with EMT-related transcription factors and signalling pathways. In the present review, we comprehensively described the EMT-inducing lncRNA molecular mechanisms and functional perspectives of EMT-inducing lncRNAs in GC progression. Taken together, the statements of this review provided a clinical implementation in identifying lncRNAs as potential therapeutic targets for advanced GC.
Antigenicity is preserved with fixative solutions used in human gross anatomy: A mice brain immunohistochemistry study
Authors: Frigon Eve-Marie , Dadar Mahsa , Boire Denis , Maranzano Josefina
Published: October 2022

Background

Histology remains the gold-standard to assess human brain biology, so ex vivo studies using tissue from brain banks are standard practice in neuroscientific research. However, a larger number of specimens could be obtained from gross anatomy laboratories. These specimens are fixed with solutions appropriate for dissections, but whether they also preserve brain tissue antigenicity is unclear. Therefore, we perfused mice brains with solutions used for human body preservation to assess and compare the tissue quality and antigenicity of the main cell populations.

Materials and methods

Twenty-eight C57BL/6J mice were perfused with 4% formaldehyde (FAS, N = 9), salt-saturated solution (SSS, N = 9), and alcohol solution (AS, N = 10). The brains were cut into 40 μm sections for antigenicity analysis and were assessed by immunohistochemistry of four antigens: neuronal nuclei (NeuN), glial fibrillary acidic protein (GFAP astrocytes), ionized calcium-binding adaptor molecule 1 (Iba1-microglia), and myelin proteolipid protein (PLP). We compared the fixatives according to multiple variables: perfusion quality, ease of manipulation, tissue quality, immunohistochemistry quality, and antigenicity preservation.

Results

The perfusion quality was better using FAS and worse using AS. The manipulation was very poor in SSS brains. FAS- and AS-fixed brains showed higher tissue and immunohistochemistry quality than the SSS brains. All antigens were readily observed in every specimen, regardless of the fixative solution.

Conclusion

Solutions designed to preserve specimens for human gross anatomy dissections also preserve tissue antigenicity in different brain cells. This offers opportunities for the use of human brains fixed in gross anatomy laboratories to assess normal or pathological conditions.
New onset episodic vertigo as a presentation of vestibular neuritis
Authors: Tang Lu , Jiang Weiwei , Wang Xiaoshan
Published: October 2022

Objective

Vestibular neuritis (VN) is a common peripheral cause of acute vestibular syndrome, characterized by sustained vertigo and gait instability, persisting from 1 day to several weeks. With the widespread use of comprehensive vestibular function tests, patients with VN and non-sustained vertigo have drawn attention. In this study, we retrospectively analyzed the clinical presentation of patients with VN and episodic vertigo, aiming to expand the atypical clinical features of VN.

Methods

This retrospective study enrolled 58 patients with VN. Among them, 11 patients with more than 3 remissions per day, each lasting over 1 h were assigned to the episodic vertigo (EV) group, and 47 subjects without significant relief into the sustained vertigo (SV) group. Demographic information, clinical manifestations and data of supplementary examinations were collected and statistically analyzed. These patients were followed up 1 year after discharge to gather prognostic information.

Results

The incidence of spontaneous nystagmus (SN) and proportion of severe vertigo (Dizziness Handicap Inventory questionnaire score >60) in the SV group were significantly higher than those in the EV group. Spearman correlation showed that with a longer disease course, the velocity of overt saccade was smaller (p < 0.05, Rs = −0.263) in all patients with VN.

Conclusion

The non-sustained manifestations in VN overlap with a wider spectrum of other vestibular disorders and stroke-related vertigo, which add an additional layer of complexity to the differential diagnosis of new onset episodic vertigo. By retrospectively analyzing the clinical characteristics and vHIT parameters, our study has expounded on the atypical features and potential pathophysiological mechanism of episodic syndromes in VN. VOR gain and saccades measured by vHIT could be reliable indicators for vestibular rehabilitation process.
Non-contact neuromodulation of the human autonomic nervous system function via different odors: Sex, menstrual cycle, and odor dose- and duration-specific effects
Authors: Maharjan Ashim , Khwaounjoo Prashanna , Peng Mei , Cakmak Yusuf Ozgur
Published: October 2022

In recent decades, it has been uncovered that the autonomic nervous system (ANS) can be influenced using non-contact neuromodulation via odor stimulation. Increasing parasympathetic-vagal activation of the ANS is integral to improving the sympathovagal balance between the sympathetic- and parasympathetic nervous systems, which is often imbalanced in several chronic inflammatory disorders, such as rheumatoid arthritis and inflammatory bowel diseases. Although research into olfactory stimulation has been observed on the ANS, it is still lacking in the exploration of odor concentration and odor-specific effects. This is particularly the case as research has not utilized specified tools, such as the olfactometer to provide precise odor delivery. Furthermore, no research has compared the results in separate sex cohorts to investigate the role of sex or the menstrual stage on the subsequent interactions. In this study, we investigated the olfactory stimulation effects of four natural odors (mushroom, lavender, jasmine, and rose) in three concentrations (low, moderate, and high) on the ANS. To observe activity from the ANS, we used an electrocardiogram (ECG) based heart rate variability (HRV) and eye-tracker technology (pupil diameter). We found for the first time in literature that there were acute dose- and duration-specific odor effects of odors on the ANS. We also found sex and menstrual cycle effects in this interaction. Furthermore, there were stark distinctions in sympathovagal activity dependent ANS activation (HRV) in comparison to the oculomotor nerve-parasympathetic/cervical sympathetic nerves dependent ANS responses (pupil diameter). Sympathovagal activity dependent HRV showed odor, sex, and menstrual-stage interactions in both divisions of the ANS while the pupil responses only indicated increased sympathetic activation. These results shed light on the use of odor-specific stimulation to modulate the ANS activity in the context of sex and the menstrual stage. Future studies should be performed using a chronic odor delivery design to investigate the long-term effects of odors on the ANS.

Clinical trial registration

Australian New Zealand Clinical Trials Registry, identifier [ACTRN12622000415707].
Expression and potential role of FOSB in glioma
Authors: Qi Min , Sun Le-an , Zheng Lan-rong , Zhang Jia , Han Yan-ling , Wu Feng , Zhao Jian , Niu Wen-hao , Fei Mao-xing , Jiang Xiao-chun , Zhou Meng-liang
Published: October 2022

Background

FOSB is reported to be an oncogene in a variety of tumors. However, the expression and role of FOSB in glioma remain obscure. In this study, we aimed to explore the expression of FOSB in glioma and its biological role in glioblastoma multiforme (GBM).

Methods

Western blot, immunohistochemical staining, and quantitative real-time polymerase chain reaction (RT-qPCR) were used to detect the expression of FOSB in clinical samples. FOSB was knocked down in cells to determine the effects of FOSB on the phenotypic changes of tumors by plate cloning, CCK-8 assay, and Transwell assay. Finally, subcutaneous tumorigenesis in nude mice was used to observe the tumorigenesis of glioma cell lines after the knockdown of the FOSB gene.

Results

FOSB expression was higher in glioma compared with normal brain tissue. After the downregulation of FOSB, the expression of cleaved caspase-3 increased. Plate cloning and CCK-8 experiments showed that the proliferation of glioma cell lines decreased. The Transwell assay demonstrated that the glioblastoma cell lines had lower migration ability after the knockdown of FOSB. Finally, the tumor volume of U87 glioma cells in group sh-FOSB was smaller than that in the control group. The TUNEL staining in vitro showed that the apoptosis of sh-FOSB glioma cells increased.

Conclusion

FOSB was highly expressed in glioma tissues. The viability of glioma cells decreased, and the ability of glioma cells to proliferate and migrate was reduced when FOSB was downregulated. Hence, FOSB may promote the development and migration of gliomas.