bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and efficacy of thermal ablation for cervical metastatic lymph nodes in papillary thyroid carcinoma: A systematic review and meta-analysis
Authors: Tang Wanqing , Tang Xiuyun , Jiang Danni , Zhang Xiaojuan , Wang Rongling , Niu Xiaoyan , Zang Yichen , Zhang Mingzhu , Wang Xinya , Zhao Cheng
Published: August 2022

Background

To evaluate the safety and efficacy of radiofrequency ablation (RFA), microwave ablation (MWA), and laser ablation (LA) for the treatment of cervical metastatic lymph nodes (CMLNs) of papillary thyroid carcinoma (PTC).

Methods

The Pubmed, EMBASE, Web of Science, and Cochrane Library databases were searched for studies on the safety and efficacy of thermal ablations (RFA, MWA, and LA) for the treatment of CMLNs of PTC until March 30, 2022. A review of 334 potential papers identified 17 eligible papers including 312 patients. Fixed-effects model or random-effects model was used to evaluate the pooled proportions of volume reduction rate (VRR), complete disappearance, and recurrence, and pooled estimates of changes in the largest diameter, volume, and serum Tg after ablation. The pooled proportions of overall and major complications were calculated. Subgroup analysis based on treatment modalities. The heterogeneity among studies was analyzed by using Q statistics and inconsistency index I2. MINORS scale was used to evaluate the quality of the studies.

Results

17 eligible studies were finally identified, including 312 patients and 559 CMLNs. The pooled proportions of VRR, complete disappearance and recurrence of CMLNs were 91.28% [95% confidence interval (CI): 86.60-95.97%], 67.9% [95% CI: 53.1-81.1%] and 7.8% [95%CI: 3.0-14.1%], respectively. The pooled estimates of changes in the largest diameter, volume and serum Tg were 8.12 mm [95%CI: 6.78-9.46 mm], 338.75 mm3 [95%CI: 206.85 -470.65 mm3] and 5.96 ng/ml [95%CI: 3.68-8.24 ng/ml], respectively. The pooled proportions of overall and major complications were 2.9% [95%CI: 0.3-7.1%] and 0.3% [95%CI: 0-1.9%], respectively. Significant between-study heterogeneity was observed for complete disappearance (P<0.01, I2 =88.6%), VRR (P<0.001, I2 =99.9%), recurrence (P=0.02, I2 =47.76%), overall complications (P<0.02, I2 =44.8%), and changes in the largest diameter (P < 0.001, I2 =82.6%), volume (P<0.001, I2 =97.0%), and serum Tg (P < 0.001, I2 =93.7%). Subgroup analysis showed heterogeneity of the VRR among the treatment modality (I2 range: 84.4-100%). The VRR of MWA was the highest (97.97%), followed by RFA (95.57%) and LA (84.46%) (P < 0.001).

Conclusion

All thermal ablations were safe and effective for the treatment of CMLNs of PTC. However, each treatment had significant heterogeneity in VRR. Compared with RFA and MWA, LA was less effective in reducing the volume of CMLNs of PTC.
Development of drift-flux correlations for vertical forward bubble column-type gas-liquid lead-bismuth two-phase flow
Authors: Wang Di , Lu Xianghui , Qiu Suizheng , Liang Ren , Lin Zhikang , Ouyang Yong
Published: August 2022

Bubble columns represent an extreme case of gas-liquid two-phase flow, where net liquid velocity is zero and the gas simply bubbles up through the liquid. The bubble column-type gas-liquid metal two-phase flow always appears in an accident scenario for pool-type lead-bismuth eutectic cooled fast breeder reactors. To accurately predict the void fraction for the accident evaluation and design of a reactor system, nine existing drift-flux type constitutive correlations are evaluated with a nitrogen-liquid heavy metal two-phase flow test. Few correlations give a relatively good prediction and the basic assumption in the distribution parameter calculation is not applicable for a bubble column. To solve this problem, analysis based on Clark’s theoretical model is carried out. The results show that the distribution parameter assumes very high values at a low Re number. As the Froude number increases, the distribution parameter tends to decrease. At lower void factions, the distribution parameter is also assumed to be at high values. This indicates that the pipe size, flow rate, and void fraction can all influence the distribution parameter. Considering the quantitative laws of these influence factors obtained by theoretical analysis and fitting the data of Ariyoshi’s test, a new correlation for a bubble column-type gas-LBE two-phase flow is developed and evaluated. The results of the statistical analysis show that the new correlation gives the best prediction for gas-LBE two-phase flow in the void fraction range of 0.018–0.313.
Spatial differentiation and influencing factors of rural-area multi-functionality in Hebei province based on a spatial econometric model
Authors: Ma Lijun , Xu Shuang , Guo Fengyu , Xu Lei , Yin Shi
Published: August 2022

The main objectives of the study are to establish a rural-area multi-functionality evaluation index system, reveal the characteristics and identify influencing factors of rural-area multi-functionality differentiation in Hebei Province. A back-propagation neural network model and a spatial econometric model were used in the study. The results of this study as follows. The spatial differentiation of rural-area multi-functionality shows the opposite distribution to that of the agricultural production and economic development functions. The distribution of the socio-cultural function was found to be opposite to that of the ecological function, while the distribution of the socio-cultural function was found to be similar to that of the economic development function. There was a positive spatial correlation between rural functional patterns. The difference in rural-area multi-functionality development conditions was found to be the main reason for agglomeration distribution differences. The agricultural production function is mainly affected by agricultural, ecological, and industrial conditions. The function of economic development was found to be mainly affected by population and traffic conditions. The socio-cultural functions were found to be mainly affected by population and economic conditions. The ecological function was greatly affected by agricultural, population, and ecological conditions. This study provides further insights into the functions of rural regions and enriches the theories used in rural regional studies by closely analyzing the causes of the generation of and changes in rural-area multi-functionality. In the future, the government department should strengthen the construction of transportation, agricultural infrastructure, and industrial infrastructure.
Groundwater depth alters soil nutrient concentrations in different environments in an arid desert
Authors: Zhang Bo , Zeng Fanjiang , Gao Xiaopeng , Shareef Muhammad , Zhang Zhihao , Yu Qiang , Gao Yanju , Li Changjun , Yin Hui , Lu Yan , Huang Caibian , Tang Gangliang
Published: August 2022

Soil nutrients are vital for plant growth and survival and present a crucial role in terrestrial function and productivity. However, little is known about the effect mechanism of groundwater table on soil nutrients in an arid desert ecological system. This study investigated the impacts of groundwater depth on the concentrations of soil organic carbon (C), available nitrogen (N), phosphorus (P), and potassium (K) at shallow groundwater depths (0.4, 0.8, 1.2, 1.8, and 2.2 m) and field deep groundwater depths (2.5, 4.5, and 11.0 m) in a desert-oasis ecotone in Central Asia in 2015 and 2016. Soil nitrate-N, inorganic-N, soil available P, and K concentrations were significantly affected by shallow and field deep groundwater. Groundwater depths did not alter soil ammonium-N concentration. Soil organic C concentration was influenced by field deep groundwater depth. Structural equation model showed that groundwater depth directly affected soil nitrate-N and K concentrations and indirectly altered the soil inorganic-N, soil organic C and available P concentrations in shallow groundwater. Moreover, groundwater depth directly influenced soil nitrate-N and soil organic C, available P and K concentrations and indirectly affected soil inorganic-N concentration in deep groundwater. Hence, groundwater depth should be considered one of the most critical environmental factors affecting soil nutrient variation in an arid desert. This study provides new insights into the soil nutrient variation under a declining groundwater depth in a hyper-arid ecosystem.
The relationship between firms’ corporate social performance and green technology innovation: The moderating role of slack resources1
Authors: Xie Yi
Published: August 2022

This study explores the relationship between firms’ corporate social responsibility (CSR) and their “green” technology innovation in the context of a developing country with a high level of economic growth (China). Using data from listed companies, green patent authorization data from the State Intellectual Property Office, and social responsibility rating data from Rankin’s CSR Ratings of China from 2009 to 2017, we find that a higher CSR rating is highly positively correlated to green technology innovation as measured by number of green patents granted. Results indicated that corporate social performance plays a contributory role in green technology innovation. We also find that unabsorbed slack resources enhance the positive relationship between CSR rating and the number of green technology patents.
Nexuses between international trade, renewable energy, and transport services: Leading toward practical implications and trade policies
Authors: Yu Zhang , Khan Abdul Rehman , Thomas George , Jameel Kiran , Tanveer Muhammad , Janjua Laeeq
Published: August 2022

This research aims to investigate the connection between logistic indicators, trade, renewable energy, and ICT on transport services in the selected 33 developed European countries. The researchers used the panel data from the 33 developed European countries to test the hypothesis. Panel GMM is an optimal modeling choice in this study from data sets ranging from 2007 to 2020. The results revealed that transport services have a significant positive relationship with trade, renewable energy, ICT, and internet usage. Also, the logistic indicators have a significant positive connection with transport services. Furthermore, renewable energy and transport services have a significant positive association with transport services. ICT adoption positively affects road freight transport by enhancing operations’ safety, suitability, visibility, and accountability. The effectiveness of these indicators is considerably affected by transport flow predictions and resource allocation strategy. Moreover, the management of high-quality operations requires optimization, and using transport and logistic management systems for transportation services makes it feasible to get optimal outcomes.
Host competence, interspecific competition and vector preference interact to determine the vector-borne infection ecology
Authors: Chen Lifan , Chen Shiliang , Kong Ping , Zhou Liang
Published: August 2022

Understanding how ecological interactions affect vector-borne disease dynamics is crucial in the context of rapid biodiversity loss and increased emerging vector-borne diseases. Although there have been many studies on the impact of interspecific competition and host competence on disease dynamics, few of them have addressed the case of a vector-borne disease. Using a simple compartment model with two competing host species and one vector, we investigated the combined effects of vector preference, host competence, and interspecific competition on disease risk in a vector-borne system. Our research demonstrated that disease transmission dynamics in multi-host communities are more complex than anticipated. Vector preference and differences in host competence shifted the direction of the effect of competition on community disease risk, yet interspecific competition quantitatively but not qualitatively changed the effect of vector preference on disease risk. Our work also identified the conditions of the dilution effect and amplification effect in frequency-dependent transmission mode, and we discovered that adding vector preference and interspecific competition into a simple two-host-one-vector model altered the outcomes of how increasing species richness affects disease risk. Our work explains some of the variation in outcomes in previous empirical and theoretical studies on the dilution effect.
Genetic analysis of a bronze age individual from Ulug-depe (Turkmenistan)
Authors: Guarino-Vignon Perle , Marchi Nina , Chimènes Amélie , Monnereau Aurore , Kroll Sonja , Mashkour Marjan , Lhuillier Johanna , Bendezu-Sarmiento Julio , Heyer Evelyne , Bon Céline
Published: August 2022

The Oxus Civilisation (or Bactrio-Margian Archaeological Complex, BMAC) was the main archaeological culture of the Bronze Age in southern Central Asia. Paleogenetic analyses were previously conducted mainly on samples from the eastern part of BMAC. The population associated with BMAC descends from local Chalcolithic populations, with some outliers of steppe or South-Asian descent. Here, we present new genome-wide data for one individual from Ulug-depe (Turkmenistan), one of the main BMAC sites, located at the southwestern edge of the BMAC. We demonstrate that this individual genetically belongs to the BMAC cluster. Using this genome, we confirm that modern Indo-Iranian–speaking populations from Central Asia derive their ancestry from BMAC populations, with additional gene flow from the western and the Altai steppes in higher proportions among the Tajiks than the Yagnobi ethnic group.
A Novel Approach: Combining Prognostic Models and Network Pharmacology to Target Breast Cancer Necroptosis-Associated Genes
Authors: Yan Congzhi , Liu Conghui , Wu Zhixuan , Dai Yinwei , Xia Erjie , Hu Wenjing , Dai Xuanxuan
Published: August 2022

Breast cancer (BC) accounts for the highest proportion of the all cancers among women, and necroptosis is recognized as a form of caspase-independent programmed cell death. We created prognostic signatures using univariate survival analysis, and lasso regression, to assess immune microenvironments between subgroups. We then used network pharmacology to bind our drugs to target differentially expressed genes (DEGs). A signature comprising a set of necroptosis-related genes was established to predict patient outcomes based on median risk scores. Those above and below the median were classified as high-risk group (HRG) and low-risk group (LRG), respectively. Patients at high risk had lower overall survival, and poorer predicted tumor, nodes, and metastases stages (TNM). The novel prognostic signature can effectively predict the prognosis of breast cancer patients docking of β,β-dimethyl acryloyl shikonin (DMAS) to possible targets to cure breast cancer. We found that all current prognostic models do not offer suitable treatment options. In additional, by docking drugs DMAS that have been initially validated in our laboratory to treat breast cancer. We hope that this novel approach could contribute to cancer research.
Development and validation of immune-based biomarkers and deep learning models for Alzheimer’s disease
Authors: He Yijie , Cong Lin , He Qinfei , Feng Nianping , Wu Yun
Published: August 2022

Background: Alzheimer’s disease (AD) is the most common form of dementia in old age and poses a severe threat to the health and life of the elderly. However, traditional diagnostic methods and the ATN diagnostic framework have limitations in clinical practice. Developing novel biomarkers and diagnostic models is necessary to complement existing diagnostic procedures.

Methods: The AD expression profile dataset GSE63060 was downloaded from the NCBI GEO public database for preprocessing. AD-related differentially expressed genes were screened using a weighted co-expression network and differential expression analysis, and functional enrichment analysis was performed. Subsequently, we screened hub genes by random forest, analyzed the correlation between hub genes and immune cells using ssGSEA, and finally built an AD diagnostic model using an artificial neural network and validated it.

Results: Based on the random forest algorithm, we screened a total of seven hub genes from AD-related DEGs, based on which we confirmed that hub genes play an essential role in the immune microenvironment and successfully established a novel diagnostic model for AD using artificial neural networks, and validated its effectiveness in the publicly available datasets GSE63060 and GSE97760.

Conclusion: Our study establishes a reliable model for screening and diagnosing AD that provides a theoretical basis for adding diagnostic biomarkers for the AD gene.
The landscape of circular RNA in preterm birth
Authors: Ran Yuxin , Chen Ruixin , Huang Dongni , Qin Yan , Liu Zheng , He Jie , Mei Youwen , Zhou Yunqian , Yin Nanlin , Qi Hongbo
Published: August 2022

Background

Preterm birth (PTB) is a multifactorial syndrome that seriously threatens the health of pregnant women and babies worldwide. Recently, circular RNAs (circRNAs) have been understood as important regulators of various physiological and pathological processes. However, the expression pattern and potential roles of circRNAs in PTB are largely unclear.

Methods

In this study, we extracted and analyzed the circRNA expression profiles in maternal and fetal samples of preterm and term pregnancies, including maternal plasma, maternal monocytes, myometrium, chorion, placenta, and cord blood. We identified the circRNAs which is associated with PTB in different tissues and explored their relationships from the perspective of the overall maternal-fetal system. Furthermore, co-expression analysis of circRNAs and mRNAs, target microRNAs (miRNAs), and RNA-binding proteins (RBPs), provided new clues about possible mechanisms of circRNA function in PTB. In the end, we investigated the potential special biofunctions of circRNAs in different tissues and their common features and communication in PTB.

Results

Significant differences in circRNA types and expression levels between preterm and term groups have been proved, as well as between tissues. Nevertheless, there were still some PTB-related differentially expressed circRNAs (DECs) shared by these tissues. The functional enrichment analysis showed that the DECs putatively have important tissue-specific biofunctions through their target miRNA and co-expressed mRNAs, which contribute to the signature pathologic changes of each tissue within the maternal-fetal system in PTB (e.g., the contraction of the myometrium). Moreover, DECs in different tissues might have some common biological activities, which are mainly the activation of immune-inflammatory processes (e.g., interleukin1/6/8/17, chemokine, TLRs, and complement).

Conclusions

In summary, our data provide a preliminary blueprint for the expression and possible roles of circRNAs in PTB, which lays the foundation for future research on the mechanisms of circRNAs in PTB.
Case report: Mycobacterium neoaurum infection during ICI therapy in a hepatocellular carcinoma patient with psoriasis
Authors: Pang Ling , Chen Zhongju , Xu Dong , Cheng Weiting
Published: August 2022

We report here a patient with advanced hepatocellular carcinoma (HCC) and psoriasis treated with immune checkpoint inhibitor (ICI) therapy who experienced tumor partial response and psoriatic exacerbation. Meanwhile, the patient contracted mycobacterium neoaurum during the treatment period, while it was an opportunistic infection and mainly happened in immunosuppressed patients. We discussed the possibility that this infection was an ICI-associated infection independent of immunosuppression due to dysregulated immunity, which was the result of the effects of immunotherapy and autoimmune disease (AID), and the characteristics and treatment of M. neoaurum, which was rarely reported in China. This case highlights the fact that some infections can be precipitated by ICIs in the absence of immunosuppressive treatment, especially the patients with AID.
Nanomaterials: A powerful tool for tumor immunotherapy
Authors: Chen Ziyin , Yue Ziqi , Wang Ronghua , Yang Kaiqi , Li Shenglong
Published: August 2022

Cancer represents the leading global driver of death and is recognized as a critical obstacle to increasing life expectancy. In recent years, with the development of precision medicine, significant progress has been made in cancer treatment. Among them, various therapies developed with the help of the immune system have succeeded in clinical treatment, recognizing and killing cancer cells by stimulating or enhancing the body’s intrinsic immune system. However, low response rates and serious adverse effects, among others, have limited the use of immunotherapy. It also poses problems such as drug resistance and hyper-progression. Fortunately, thanks to the rapid development of nanotechnology, engineered multifunctional nanomaterials and biomaterials have brought breakthroughs in cancer immunotherapy. Unlike conventional cancer immunotherapy, nanomaterials can be rationally designed to trigger specific tumor-killing effects. Simultaneously, improved infiltration of immune cells into metastatic lesions enhances the efficiency of antigen submission and induces a sustained immune reaction. Such a strategy directly reverses the immunological condition of the primary tumor, arrests metastasis and inhibits tumor recurrence through postoperative immunotherapy. This paper discusses several types of nanoscale biomaterials for cancer immunotherapy, and they activate the immune system through material-specific advantages to provide novel therapeutic strategies. In summary, this article will review the latest advances in tumor immunotherapy based on self-assembled, mesoporous, cell membrane modified, metallic, and hydrogel nanomaterials to explore diverse tumor therapies.
North Pacific minke whales call rapidly when calling conspecifics are nearby
Authors: Martin Cameron R. , Guazzo Regina A. , Helble Tyler A. , Alongi Gabriela C. , Durbach Ian N. , Martin Stephen W. , Matsuyama Brian M. , Henderson E. Elizabeth
Published: August 2022

North Pacific minke whale (Balaenoptera acutorostrata) boing calls are commonly detected in Hawaiian waters. When producing boing vocalizations, minke whales seem to be in one of two calling behavioral states. Most often minke whales produce boings with inter-call intervals of several minutes, but sometimes minke whales call rapidly with inter-call intervals of less than a minute. Since minke whales are difficult to detect visually, cue-rate-based density estimation using passive acoustic monitoring has been proposed. However, the variables that influence cue rate or calling rate are poorly understood in most whales, including minke whales. We collected passive acoustic recordings from 47 bottom-mounted hydrophones at the Pacific Missile Range Facility’s instrumented range off the coast of Kauaʻi, Hawaiʻi to test the hypothesis that minke whales call more rapidly when closer in proximity to other calling conspecifics. A total of 599 days of data were recorded between August 2012 and July 2017 and were automatically post-processed to detect, classify, and localize calls. Localized calls were grouped into tracks and manually validated, resulting in 509 individual tracks composed of 36,033 calls within a 16 x 39 km focal study area. Tracked minke whales exhibited a strong bimodal call rate with means of one call every 6.85 min (σ= 2.54 min) and 0.63 min (σ= 0.36 min). We ran hidden Markov models to quantify the relationship between call rate and the distance to the nearest calling conspecific. Overall, the probability of the higher call rate occurring increased as the distance to the nearest conspecific decreased, and the probability of the lower call rate occurring increased as the distance to the nearest conspecific increased. We also examined individual track data and found that minke whales may also exhibit other responses (i.e. increased speed, changes in heading, and cessation of calling) when calling conspecifics are nearby. These findings provide new information about minke whale calling behavior in what is likely a breeding area.
Study of dynamic hole-forming performance of a cup-hanging planter on a high-speed seedling transplanter
Authors: Yang Qizhi , Zhang Ruoyu , Jia Cuiping , Li Zhangyan , Zhu Menglan , Addy M.
Published: August 2022

Due to the advantages of hole forming and transplanting at the same time, even on a film-covered field ridge, the cup-hanging transplanter has become one of the most widely used transplanters in agricultural operations. The cup-hanging planter is the main operating part of the transplanter. Different shapes of the hanging cup can affect the soil action mechanism, cavitation performance, and planting quality. In this study, the discrete element simulation software EDEM and the multi-body system dynamics analysis software RecurDyn are used to carry out the coupling simulation analysis. The results showed that the planting holes formed by hanging cups with two different shapes and under four different planting frequencies all met the planting requirements. After soil reflow, the transverse dimensions of the two holes are similar, and the longitudinal dimensions of the hole of the conical hanging cup are smaller than those of the multilateral hanging cup. Under the same planting frequency, the tear film size and hole-forming performance of the conical cup were better than those of the multilateral hanging cup. The result of the simulation test is consistent with that of the bench test, which proved the feasibility of using EDEM-RecurDyn coupling simulation to predict the hole-forming characteristics of the cup-hanging planter. The filmless hole-forming performances of two different shapes of hanging cups are close to each other. In terms of the film damage of film hole-forming, the conical cup is better than that of the multilateral hanging cup.
Incidence and characteristics of adverse drug reactions in a cohort of patients treated with PD-1/PD-L1 inhibitors in real-world practice
Authors: Sabaté Gallego Mònica , Pérez Esquirol Eulàlia , Garcia Doladé Núria , Vidal Guitart Xavier , Carreras Soler Maria-Josep , Farriols Danés Anna , Felip Enriqueta , Braña Irene , Carles Galceran Joan , Morales Barrera Rafael , Muñoz-Couselo Eva , Agustí Escasany Antònia
Published: August 2022

Background

Data related to adverse drug reactions (ADRs), specifically immune-related adverse events (irAEs), in long-term treatment with immunotherapy in real-world practice is scarce, as is general information regarding the management of ADRs.

Objectives

To characterize and describe the incidence of ADRs in patients who began immunotherapy treatment in clinical practice.

Methods

In a prospective observational study cancer patients ≥18 years of age who were treated with a monotherapy regime of PD-1/PD-L1 inhibitors were evaluated. The study period was from November 2017 to June 2019 and patients were followed up until June 2021. Patients were contacted monthly by telephone and their electronic health records were reviewed. Each ADR was graded according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0).

Results

Out of 99 patients, 86 met the inclusion criteria. Most were male (67.4%), with a median age of 66 (interquartile range, IQR: 59–76). The most frequent cancer was non-small cellular lung cancer (46 cases, 53.5%), followed by melanoma (22, 25.6%). A total of 74 patients (86%) were treated with anti-PD-1 drugs and 12 (14%) were treated with anti-PD-L1 drugs. The median treatment durations were 4.9 (IQR: 1.9–17.0) and 5.9 months (IQR: 1.2–12.3), respectively. Sixty-three patients (73%) developed from a total of 156 (44% of the total number of ADR) irADRs, wherein the most frequent were skin disorders (50 cases, 32%, incidence = 30.5 irADRs/100 patients per year [p-y]), gastrointestinal disorders (29, 19%, 17.7 irADRs/100 p-y), musculoskeletal disorders (17, 11%, 10.4 irADRs/100 p-y), and endocrine disorders (14, 9%, 8.6 irADRs/100 p-y). A total of 22 irADRs (14%) had a latency period of ≥12 months. Twelve irADRs (7.7%) were categorized as grade 3–4, and while 2 (1.3%) were categorized as grade 5 (death). Sixty-one irADRs (39.1%) in 36 patients required pharmacological treatment and 47 irADRs (30.1%) in 22 patients required treatment with corticosteriods.

Conclusion

The majority of patients treated with anti-PD1/PDL1-based immunotherapy experienced adverse reactions. Although most of these reactions were mild, 11.5% were categorized as grade 3 or above. A high percentage of the reactions were immune-related and occurred throughout the treatment, thereby indicating that early identification and close monitoring is essential.
Prognostic value of proadrenomedullin in patients with COVID-19 pneumonia
Authors: Astapovskii Aleksandr A. , Drozdov Vladimir N. , Shikh Evgenia V. , Melkonyan George G. , Sizova Zhanna M. , Zakharova Valeria L. , Shindryaeva Natalia N. , Lapidus Natalia I.
Published: August 2022

Objective

The aim of the study was to assess the role of mid-regional proadrenomedullin (MR-proADM) in comparison with routine laboratory tests in patients with COVID-19.

Materials and methods

140 hospitalized patients aged 18 and older with COVID-19 pneumonia were included in prospective single-center study. Routine analyses were performed, and MR-proADM level was measured within the first and the third hospital days using Human MR pro-ADM (Mid-regional pro-adrenomedullin) ELISA Kit with a sensitivity of 0.469 pmol/L (immunofluorescence assay). National Early Warning Score (NEWS) was used for primary assessment of the disease severity. According to disease outcome the patients were divided into two groups: discharged patients (n = 110, 78.6%) and deceased patients (n = 30, 21.4%). Results: The groups had no statistically significant difference in sex, comorbidity, body temperature, oxygen saturation level, heart rate, respiratory rate, and C-reactive protein (CRP) level and procalcitonin (PCT). The deceased patients had statistically significant difference in age (median, 76 years; interquartile range, 73.2–78.2 vs. median, 66 years; interquartile range, 62–67; p < 0.0001), NEWS value (median, 5; interquartile range, 3–8 vs. median, 2; interquartile range, 0–6; p <0.05), hospitalization period (median, 17; interquartile range, 7–35 vs. median, 6; interquartile range, 3–14), quantitative CT extent of lung damage > 50% [n = 26 (86.7%) vs. n = 9 (8.2%) p < 0.0001], level of leukocytes (median, 11.4 ×109/L; interquartile range, 6.2–15.5 vs. median, 5.3 ×109/L; interquartile range, 4.7–6.4; p = 0.003), level of neutrophils (median, 80.9%; interquartile range, 73.6–88.6 vs. median, 72.6%; interquartile range, 68.7–76.9; p = 0.027), level of MR-proADM at the first hospital day (median, 828.6 pmol/L; interquartile range, 586.4–1,184.6 vs. median, 492.6 pmol/L; interquartile range, 352.9–712.2; p = 0.02), and level of MR-proADM at the third hospital day (median, 1,855.2 pmol/L; interquartile range, 1,078.4–2,596.5 vs. median, 270.7 pmol/L; interquartile range, 155.06–427.1).

Conclusion

Mid-regional proadrenomedullin has a higher prognostic value in patients with COVID-19 in comparison with routine inflammatory markers (leukocyte and neutrophils levels, CRP, and PCT) and NEWS.
Decolonization of carbapenem-resistant Klebsiella pneumoniae from the intestinal microbiota of model mice by phages targeting two surface structures
Authors: Liu Ju-Yun , Lin Tzu-Lung , Chiu Ching-Yu , Hsieh Pei-Fang , Lin Yi-Tsung , Lai Li-Yin , Wang Jin-Town
Published: August 2022

Background

Klebsiella pneumoniae is a normal component of the human gastrointestinal tract microbiota. However, in some cases, it can cause disease. Over the past 20 years, the prevalence of antibiotic-resistant bacteria, such as carbapenem-resistant K. pneumoniae (CRKP), has been increasing.

Materials and methods

We attempted to specifically eliminate CRKP from a mouse model with the human intestinal microbiota. To establish humanized microbiota-colonized mice, we administered K64 CRKP-containing human microbiota to germ-free mice by fecal microbiota transplantation. Then, we used two phages, one targeting the capsule (φK64-1) and one targeting O1 lipopolysaccharide (φKO1-1) of K64 K. pneumoniae, to eliminate CRKP.

Results

In untreated control and φKO1-1-treated K64-colonized mice, no change in CRKP was observed, while in mice treated with φK64-1, a transient reduction was observed. In half of the mice treated with both φKO1-1 and φK64-1, CRKP was undetectable in feces by PCR and culture for 60 days. However, in the other 50% of the mice, K. pneumoniae was transiently reduced but recovered 35 days after treatment.

Conclusion

Combination treatment with φK64-1 and φKO1-1 achieved long-term decolonization in 52.3% of mice carrying CRKP. Importantly, the composition of the intestinal microbiota was not altered after phage treatment. Therefore, this strategy may be useful not only for eradicating drug-resistant bacterial species from the intestinal microbiota but also for the treatment of other dysbiosis-associated diseases.
Dimethyl phthalate destroys the cell membrane structural integrity of Pseudomonas fluorescens
Authors: Chen Wenjing , Guo Ruxin , Wang Zhigang , Xu Weihui , Hu Yunlong
Published: August 2022

A Gram-negative bacteria (Pseudomonas fluorescens) was exposed to different concentrations (0, 20, and 40 mg/L) of dimethyl phthalate (DMP) for 8 h, and then Fourier transform infrared spectroscopy (FTIR) analysis, lipopolysaccharide content detection, analysis of fatty acids, calcein release test, proteomics, non-targeted metabolomics, and enzyme activity assays were used to evaluate the toxicological effect of DMP on P. fluorescens. The results showed that DMP exposure caused an increase in the unsaturated fatty acid/saturated fatty acid (UFA/SFA) ratio and in the release of lipopolysaccharides (LPSs) from the cell outer membrane (OM) of P. fluorescens. Moreover, DMP regulated the abundances of phosphatidyl ethanolamine (PE) and phosphatidyl glycerol (PG) of P. fluorescens and induced dye leakage from an artificial membrane. Additionally, excessive reactive oxygen species (ROS), malondialdehyde (MDA), and changes in antioxidant enzymes (i.e., catalase [CAT] and superoxide dismutase [SOD]) activities, as well as the inhibition of Ca2+-Mg2+-ATPase and Na+/K+-ATPase activities in P. fluorescens, which were induced by the DMP. In summary, DMP could disrupt the lipid asymmetry of the outer membrane, increase the fluidity of the cell membrane, and destroy the integrity of the cell membrane of P. fluorescens through lipid peroxidation, oxidative stress, and ion imbalance.
Long non-coding RNAs play an important regulatory role in tumorigenesis and tumor progression through aerobic glycolysis
Authors: Fan Ni , Fu Hui , Feng Xuchen , Chen Yatong , Wang Jingyu , Wu Yuqi , Bian Yuhong , Li Yingpeng
Published: August 2022

Compared to normal cells, cancer cells generate ATP mainly through aerobic glycolysis, which promotes tumorigenesis and tumor progression. Long non-coding RNAs (LncRNAs) are a class of transcripts longer than 200 nucleotides with little or without evident protein-encoding function. LncRNAs are involved in the ten hallmarks of cancer, interestingly, they are also closely associated with aerobic glycolysis. However, the mechanism of this process is non-transparent to date. Demonstrating the mechanism of lncRNAs regulating tumorigenesis and tumor progression through aerobic glycolysis is particularly critical for cancer therapy, and may provide novel therapeutic targets or strategies in cancer treatment. In this review, we discuss the role of lncRNAs and aerobic glycolysis in tumorigenesis and tumor progression, and further explore their interaction, in hope to provide a novel therapeutic target for cancer treatment.
A single molecule investigation of i-motif stability, folding intermediates, and potential as in-situ pH sensor
Authors: Mustafa Golam , Gyawali Prabesh , Taylor Jacob A. , Maleki Parastoo , Nunez Marlon V. , Guntrum Michael C. , Shiekh Sajad , Balci Hamza
Published: August 2022

We present a collection of single molecule work on the i-motif structure formed by the human telomeric sequence. Even though it was largely ignored in earlier years of its discovery due to its modest stability and requirement for low pH levels (pH < 6.5), the i-motif has been attracting more attention recently as both a physiologically relevant structure and as a potent pH sensor. In this manuscript, we establish single molecule Förster resonance energy transfer (smFRET) as a tool to study the i-motif over a broad pH and ionic conditions. We demonstrate pH and salt dependence of i-motif formation under steady state conditions and illustrate the intermediate states visited during i-motif folding in real time at the single molecule level. We also show the prominence of intermediate folding states and reversible folding/unfolding transitions. We present an example of using the i-motif as an in-situ pH sensor and use this sensor to establish the time scale for the pH drop in a commonly used oxygen scavenging system.
Intact maternal buffering of stress response in infant rats despite altered responsivity towards maternal olfactory cues in the valproic acid model of autism-like behavior
Authors: White Amanda M. , An Xianli , Debiec Jacek
Published: August 2022

Disrupted processing of social cues and altered social behaviors are among the core symptoms of autism spectrum disorders (ASDs), and they emerge as early as the first year of life. These differences in sensory abilities may affect the ability of children with ASDs to securely attach to a caregiver and experience caregiver buffering of stress. Prenatal exposure to valproic acid (VPA) has been used to model some aspects of ASDs in rodents. Here, we asked whether prenatal VPA exposure altered infant rats’ behavioral responsivity to maternal olfactory cues in an Odor Preference Test (OPT) and affected maternal buffering of infants’ stress responsivity to shock. In the odor preference test, 1-week old rats treated with VPA during pregnancy appeared to have impaired social recognition and/or may be less motivated to approach social odors in early infancy. These effects were particularly prominent in female pups. In 2-week old rats, VPA-exposed pups and saline-exposed pups showed similar preferences for home cage bedding. Although VPA-exposed pups may initially have a deficit in this attachment-related behavior they do recover typical responses to home cage bedding in later infancy. Both control and VPA-exposed pups showed robust stress hormone responses to repeated shocks, an effect which was blocked when a calm mother was present during shock exposure. No sex differences in the effect of maternal presence on the stress response to shock and no interactions between sex and prenatal drug exposure were observed. Although VPA-exposed pups may show impaired responsivity to maternal cues in early infancy, maternal presence is still capable of regulating the stress response in VPA-exposed pups. In this study we demonstrate the importance of utilizing multiple batteries of tests in assessing behavior, dissecting the behavior on one test into different components. Our results inform about the underlying behavioral characteristics of some of the ASD phenotypes, including sex differences reported by clinical studies, and could shed light on potential opportunities for intervention.
Tandospirone prevents stress-induced anxiety-like behavior and visceral hypersensitivity by suppressing theta oscillation enhancement via 5-HT1A receptors in the anterior cingulate cortex in rats
Authors: Zhan Ting-Ting , Dong Zhi-Yu , Yi Li-Sha , Zhang Yan , Sun Hui-Hui , Zhang Hai-Qin , Wang Jun-Wen , Chen Ying , Huang Ying , Xu Shu-Chang
Published: August 2022

Tandospirone, a third-generation of antianxiety agent with fewer side effects, has been widely used in the treatment of anxiety. Moreover, it is interesting that tandospirone has been found to relieve gastrointestinal symptoms in patients with refractory irritable bowel syndrome who also have psychological dysfunctions. However, the underlying mechanism remains unclear. In this study, using a visceral hypersensitivity rat model induced by chronic water avoidance stress to mimic the symptoms of irritable bowel syndrome, we found that tandospirone relieved anxiety-like behavior and visceral hypersensitivity induced by stress. Meanwhile, stressed rats had increased 5-HT concentration, less 5-HT1A receptor expression, and enhanced theta oscillations in the anterior cingulate cortex (ACC). Furthermore, the power of the theta band in ACC is positively correlated with the level of visceral sensitivity. Activation of 5-HT1A receptors by its agonist, 8-OH-DPAT, to compensate for their effect in ACC reduced the enhancement of theta oscillations in ACC slices in stressed rats, whereas 5-HT1A receptor antagonist, WAY100135, facilitates theta oscillations in slices of normal rats. Tandospirone reduced the enhancement of theta band power in ACC in vitro and in vivo, thus alleviating anxiety-like behavior and visceral hypersensitivity through 5-HT1A receptors in stressed rats. These results suggest a novel mechanism by which tandospirone activates 5-HT1A receptors to relieve stress-induced anxiety and visceral hypersensitivity by suppressing theta oscillation enhancement in ACC.
Predicting progression to dementia with “comprehensive visual rating scale” and machine learning algorithms
Authors: Park Chaeyoon , Jang Jae-Won , Joo Gihun , Kim Yeshin , Kim Seongheon , Byeon Gihwan , Park Sang Won , Kasani Payam Hosseinzadeh , Yum Sujin , Pyun Jung-Min , Park Young Ho , Lim Jae-Sung , Youn Young Chul , Choi Hyun-Soo , Park Chihyun , Im Hyeonseung , Kim SangYun
Published: August 2022

Background and Objective

Identifying biomarkers for predicting progression to dementia in patients with mild cognitive impairment (MCI) is crucial. To this end, the comprehensive visual rating scale (CVRS), which is based on magnetic resonance imaging (MRI), was developed for the assessment of structural changes in the brains of patients with MCI. This study aimed to investigate the use of the CVRS score for predicting dementia in patients with MCI over a 2-year follow-up period using various machine learning (ML) algorithms.

Methods

We included 197 patients with MCI who were followed up more than once. The data used for this study were obtained from the Japanese-Alzheimer's Disease Neuroimaging Initiative study. We assessed all the patients using their CVRS scores, cortical thickness data, and clinical data to determine their progression to dementia during a follow-up period of over 2 years. ML algorithms, such as logistic regression, random forest (RF), XGBoost, and LightGBM, were applied to the combination of the dataset. Further, feature importance that contributed to the progression from MCI to dementia was analyzed to confirm the risk predictors among the various variables evaluated.

Results

Of the 197 patients, 108 (54.8%) showed progression from MCI to dementia. Tree-based classifiers, such as XGBoost, LightGBM, and RF, achieved relatively high performance. In addition, the prediction models showed better performance when clinical data and CVRS score (accuracy 0.701–0.711) were used than when clinical data and cortical thickness (accuracy 0.650–0.685) were used. The features related to CVRS helped predict progression to dementia using the tree-based models compared to logistic regression.

Conclusions

Tree-based ML algorithms can predict progression from MCI to dementia using baseline CVRS scores combined with clinical data.
Ischemic and haemorrhagic stroke risk estimation using a machine-learning-based retinal image analysis
Authors: Qu Yimin , Zhuo Yuanyuan , Lee Jack , Huang Xingxian , Yang Zhuoxin , Yu Haibo , Zhang Jinwen , Yuan Weiqu , Wu Jiaman , Owens David , Zee Benny
Published: August 2022

Background

Stroke is the second leading cause of death worldwide, causing a considerable disease burden. Ischemic stroke is more frequent, but haemorrhagic stroke is responsible for more deaths. The clinical management and treatment are different, and it is advantageous to classify their risk as early as possible for disease prevention. Furthermore, retinal characteristics have been associated with stroke and can be used for stroke risk estimation. This study investigated machine learning approaches to retinal images for risk estimation and classification of ischemic and haemorrhagic stroke.

Study design

A case-control study was conducted in the Shenzhen Traditional Chinese Medicine Hospital. According to the computerized tomography scan (CT) or magnetic resonance imaging (MRI) results, stroke patients were classified as either ischemic or hemorrhage stroke. In addition, a control group was formed using non-stroke patients from the hospital and healthy individuals from the community. Baseline demographic and medical information was collected from participants' hospital medical records. Retinal images of both eyes of each participant were taken within 2 weeks of admission. Classification models using a machine-learning approach were developed. A 10-fold cross-validation method was used to validate the results.

Results

711 patients were included, with 145 ischemic stroke patients, 86 haemorrhagic stroke patients, and 480 controls. Based on 10-fold cross-validation, the ischemic stroke risk estimation has a sensitivity and a specificity of 91.0% and 94.8%, respectively. The area under the ROC curve for ischemic stroke is 0.929 (95% CI 0.900 to 0.958). The haemorrhagic stroke risk estimation has a sensitivity and a specificity of 93.0% and 97.1%, respectively. The area under the ROC curve is 0.951 (95% CI 0.918 to 0.983).

Conclusion

A fast and fully automatic method can be used for stroke subtype risk assessment and classification based on fundus photographs alone.
Phenytoin as seizure prophylaxis in hematopoietic stem cell transplantation with busulfan conditioning
Authors: Germeraad R. S. , Demandt A. M. P. , Rouhl R. P. W.
Published: August 2022

Background

Phenytoin is widely used as primary seizure prophylaxis in hematopoietic stem cell transplantation in patients undergoing myeloablative conditioning with busulfan. Because of the negative side effects of phenytoin, we abandoned phenytoin use in these patients. To assess the effect of this change, we performed a retrospective cohort study on all patients receiving busulfan.

Methods

We included 139 patients who underwent conditioning with busulfan for hematopoietic stem cell therapy. We registered the use of phenytoin, as well as the occurrence of seizures, until 7 days after busulfan administration. We compared seizure incidence between patients who received phenytoin and those who did not.

Results

Of the 43 patients who received phenytoin prophylaxis, four patients (9.3%) had a seizure during the conditioning regimen, of which two patients had cerebral non-Hodgkin lymphoma. Furthermore, all these 4 patients had very high levels of phenytoin (intoxication). Of the 96 patients that did not receive phenytoin prophylaxis, three patients (3.1%) had a seizure, and one of these patients had an undefined cerebral lesion. Phenytoin did not relate to seizure prevention in a logistic regression analysis.

Conclusion

We conclude that phenytoin prophylaxis in patients treated with busulfan is obsolete and possibly harmful, as phenytoin intoxication can occur. We recommend discontinuing the use of phenytoin as primary seizure prophylaxis in these patients.