bluuebunny/crossref_metadata_2025 huggingface dataset:
Alleviation of salinity stress by EDTA chelated-biochar and arbuscular mycorrhizal fungi on maize via modulation of antioxidants activity and biochemical attributes
Authors: Huang Ping , Huang Shoucheng , Ma Yuhan , Danish Subhan , Hareem Misbah , Syed Asad , Elgorban Abdallah M. , Eswaramoorthy Rajalakshmanan , Wong Ling Shing
Published: January 2024

Salinity stress adversely affects agricultural productivity by disrupting water uptake, causing nutrient imbalances, and leading to ion toxicity. Excessive salts in the soil hinder crops root growth and damage cellular functions, reducing photosynthetic capacity and inducing oxidative stress. Stomatal closure further limits carbon dioxide uptake that negatively impact plant growth. To ensure sustainable agriculture in salt-affected regions, it is essential to implement strategies like using biofertilizers (e.g. arbuscular mycorrhizae fungi = AMF) and activated carbon biochar. Both amendments can potentially mitigate the salinity stress by regulating antioxidants, gas exchange attributes and chlorophyll contents. The current study aims to explore the effect of EDTA-chelated biochar (ECB) with and without AMF on maize growth under salinity stress. Five levels of ECB (0, 0.2, 0.4, 0.6 and 0.8%) were applied, with and without AMF. Results showed that 0.8ECB + AMF caused significant enhancement in shoot length (~ 22%), shoot fresh weight (~ 15%), shoot dry weight (~ 51%), root length (~ 46%), root fresh weight (~ 26%), root dry weight (~ 27%) over the control (NoAMF + 0ECB). A significant enhancement in chlorophyll a, chlorophyll b and total chlorophyll content, photosynthetic rate, transpiration rate and stomatal conductance was also observed in the condition 0.8ECB + AMF relative to control (NoAMF + 0ECB), further supporting the efficacy of such a combined treatment. Our results suggest that adding 0.8% ECB in soil with AMF inoculation on maize seeds can enhance maize production in saline soils, possibly via improvement in antioxidant activity, chlorophyll contents, gas exchange and morphological attributes.
Point-of-care testing and antibiotics prescribing in out-of-hours general practice: a register-based study in Denmark
Authors: Christensen Line Due , Vestergaard Claus Høstrup , Keizer Ellen , Bech Bodil Hammer , Bro Flemming , Christensen Morten Bondo , Huibers Linda
Published: January 2024

Background

Point-of-care testing may reduce diagnostic uncertainty in case of suspicion of bacterial infection, thereby contributing to prudent antibiotic prescribing. We aimed to study variations in the use of point-of-care tests (C-reactive protein test, rapid streptococcal antigen detection test, and urine dipstick) among general practitioners (GPs) and the potential association between point-of-care testing and antibiotic prescribing in out-of-hours general practice.

Methods

We conducted a population-based observational register-based study, based on patient contacts with out-of-hours general practice in the Central Denmark Region in 2014–2017. The tendency of GPs to use point-of-care testing was calculated, and the association between the use of point-of-care testing and antibiotic prescribing was evaluated with the use of binomial regression.

Results

Out-of-hours general practice conducted 794,220 clinic consultations from 2014 to 2017, of which 16.1% resulted in an antibiotic prescription. The GP variation in the use of point-of-care testing was largest for C-reactive protein tests, with an observed variation (p90/p10 ratio) of 3.0; this means that the GPs in the 90th percentile used C-reactive protein tests three times as often as the GPs in the 10th percentile. The observed variation was 2.1 for rapid streptococcal antigen detection tests and 1.9 for urine dipsticks. The GPs who tended to use more point-of-care tests prescribed significantly more antibiotics than the GPs who tended to use fewer point-of-care tests. The GPs in the upper quintile of the tendency to use C-reactive protein test prescribed 22% more antibiotics than the GPs in the lowest quintile (21% for rapid streptococcal antigen detection tests and 8% for urine dipsticks). Up through the quintiles, this effect exhibited a positive linear dose–response correlation.

Conclusion

The GPs varied in use of point-of-care testing. The GPs who tended to perform more point-of-care testing prescribed more antibiotics compared with the GPs who tended to perform fewer of these tests.
Daily activity patterns in older adults receiving initial support: the association between daily steps and sitting in bouts of at least 60 min
Authors: Niklasson Joakim , Fagerström Cecilia , Backåberg Sofia , Lindberg Terese , Bergman Patrick
Published: January 2024

Background

Aging has a significant impact on health, underlining the importance of maintaining physical function and reducing time spent sitting among older adults. To understand how to reduce prolonged sitting or increase physical activity, factors related to the daily living and observed daily activity patterns should be explored. This study aimed to investigate the association between daily steps, self-rated health, physical activity, sedentary behavior, motivation to exercise and fear of falling among older adults receiving initial support.

Method

Cross-sectional design with total population questionnaire data from adults aged ≥ 60 years (n = 917), living at home with initial support from municipal care in southern Sweden. The older adults were offered to participate in a follow-up study measuring daily activity patterns with accelerometers (n = 72). Linear regression was used to analyze associations between daily steps and possible predictors.

Results

The linear model ($$ {R}^{2}= $$0.478) showed that sitting in unbroken bouts of > 60 min (β = -0.313, p < 0.05), walking independently outdoors (β = 0.301, p < 0.05), intending to increase physical activity (β = -0.294, p < 0.05), sex (β = 0.279, p < 0.05), relative autonomy index (β = 0.258, p < 0.05), fear of falling (β = -0.238, p < 0.05), and self-rated health (β = 0.213, p < 0.05) predicted daily steps.

Conclusion

The model of predictors brings new understanding regarding daily steps among community-dwelling older adults. The association between sitting in bouts of > 60 min and daily steps is interesting as 35% of participants had a number of sitting bouts that on average, showed 30% less steps taken. Minimizing long sitting bouts and maintaining physical functioning to promote independence when walking outdoors can be tools for clinical practitioners devising interventions to break prolonged sitting among community-dwelling older adults. Future research should prioritize studying older adults’ outdoor walking independence, including its relation to walking with or without assistive devices and its impact on physical activity and sedentary behavior.
Gene expression profiling of host lipid metabolism in SARS-CoV-2 infected patients: a systematic review and integrated bioinformatics analysis
Authors: Munawar Wan Amirul Syazwan Wan Ahmad , Elias Marjanu Hikmah , Addnan Faizul Helmi , Hassandarvish Pouya , AbuBakar Sazaly , Roslan Nuruliza
Published: January 2024

Background

The Coronavirus disease 2019 (COVID-19) pandemic occurred due to the dispersion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Severe symptoms can be observed in COVID-19 patients with lipid-related comorbidities such as obesity and diabetes. Yet, the extensive molecular mechanisms of how SARS-CoV-2 causes dysregulation of lipid metabolism remain unknown.

Methods

Here, an advanced search of articles was conducted using PubMed, Scopus, EBSCOhost, and Web of Science databases using terms from Medical Subject Heading (MeSH) like SARS-CoV-2, lipid metabolism and transcriptomic as the keywords. From 428 retrieved studies, only clinical studies using next-generation sequencing as a gene expression method in COVID-19 patients were accepted. Study design, study population, sample type, the method for gene expression and differentially expressed genes (DEGs) were extracted from the five included studies. The DEGs obtained from the studies were pooled and analyzed using the bioinformatics software package, DAVID, to determine the enriched pathways. The DEGs involved in lipid metabolic pathways were selected and further analyzed using STRING and Cytoscape through visualization by protein-protein interaction (PPI) network complex.

Results

The analysis identified nine remarkable clusters from the PPI complex, where cluster 1 showed the highest molecular interaction score. Three potential candidate genes (PPARG, IFITM3 and APOBEC3G) were pointed out from the integrated bioinformatics analysis in this systematic review and were chosen due to their significant role in regulating lipid metabolism. These candidate genes were significantly involved in enriched lipid metabolic pathways, mainly in regulating lipid homeostasis affecting the pathogenicity of SARS-CoV-2, specifically in mechanisms of viral entry and viral replication in COVID-19 patients.

Conclusions

Taken together, our findings in this systematic review highlight the affected lipid-metabolic pathways along with the affected genes upon SARS-CoV-2 invasion, which could be a potential target for new therapeutic strategies study in the future.
Developing a risk assessment tool for cancer-related venous thrombosis in China: a modified Delphi-analytic hierarchy process study
Authors: Qin Xiaoli , Gao Xiurong , Yang Yujie , Ou Shunlong , Luo Jing , Wei Hua , Jiang Qian
Published: January 2024

Objective

To develop a Risk Assessment Tool for Cancer-related Venous Thrombosis in China.

Methods

A modified two-round Delphi method was employed to establish consensus within a field to reach an agreement via a questionnaire or by interviewing a multidisciplinary panel of experts by collecting their feedback to inform the next round, exchanging their knowledge, experience, and opinions anonymously, and resolving uncertainties. Furthermore, The AHP (Analytic Hierarchy Process) was used to determine the final quality indicators’ relative importance.

Results

The expert’s positive coefficient was 85.19% in the first round and 82.61% in the second round, with authoritative coefficients of 0.89 and 0.92 in the respective surveys. The P-value of Kendall’s W test was all less than 0.001 for each round, and the W-value for concordance at the end of the two rounds was 0.115. The final Risk Assessment Tool for Cancer-related Venous Thrombosis consisted of three domains, ten subdomains, and 39 indicators, with patient factors weighing 0.1976, disease factors weighing 0.4905, and therapeutic factors weighing 0.3119.

Conclusion

The tool is significantly valid and reliable with a strong authority and coordination degree, and it can be used to assess the risk of cancer-related VTE and initiate appropriate thrombophylactic interventions in China.
Identification of a novel m6A-related lncRNAs signature and immunotherapeutic drug sensitivity in pancreatic adenocarcinoma
Authors: Li Xia-Qing , Yin Shi-Qi , Chen Lin , Tulamaiti Aziguli , Xiao Shu-Yu , Zhang Xue-Li , Shi Lei , Miao Xiao-Cao , Yang Yan , Xing Xin
Published: January 2024

Background

Pancreatic adenocarcinoma (PDAC) ranks as the fourth leading cause for cancer-related deaths worldwide. N6-methyladenosine (m6A) and long non-coding RNAs (lncRNAs) are closely related with poor prognosis and immunotherapeutic effect in PDAC. The aim of this study is to construct and validate a m6A-related lncRNAs signature and assess immunotherapeutic drug sensitivity in PDAC.

Methods

RNA-seq data for 178 cases of PDAC patients and 167 cases of normal pancreatic tissue were obtained from TCGA and GTEx databases, respectively. A set of 21 m6A-related genes were downloaded based on the previous report. Co-expression network was conducted to identify m6A-related lncRNAs in PDAC. Cox analyses and least absolute shrinkage and selection operator (Lasso) regression model were used to construct a risk prognosis model. The relationship between signature genes and immune function was explored by single-sample GSEA (ssGSEA). The tumor immune dysfunction and exclusion (TIDE) score and tumor mutation burden (TMB) were utilized to evaluate the response to immunotherapy. Furthermore, the expression levels of 4 m6A-related lncRNAs on PDAC cell lines were measured by the quantitative real-time PCR (qPCR). The drug sensitivity between the high- and low-risk groups was validated using PDAC cell lines by Cell-Counting Kit 8 (CCK8).

Results

The risk prognosis model was successfully constructed based on 4 m6A-related lncRNAs, and PDAC patients were divided into the high- and low-risk groups. The overall survival (OS) of the high-risk groups was more unfavorable compared with the low-risk groups. Receiver operating characteristic (ROC) curves demonstrated that the risk prognosis model reasonably predicted the 2-, 3- and 5-year OS of PDAC patients. qPCR analysis confirmed the decreased expression levels of 4 m6A-related lncRNAs in PDAC cells compared to the normal pancreatic cells. Furthermore, CCK8 assay revealed that Phenformin exhibited higher sensitivity in the high-risk groups, while Pyrimethamine exhibited higher sensitivity in the low-risk groups.

Conclusion

The prognosis of patients with PDAC were well predicted in the risk prognosis model based on m6A-related lncRNAs, and selected immunotherapy drugs have potential values for the treatment of pancreatic cancer.
The effect of parental regulatory focus on the loneliness stigma of college children
Authors: Fan Zhiguang , Shi Xiaoli , Zhang Wei , Zhang Bin
Published: January 2024

Background

The present study aimed to examine the relationship between regulatory focus and loneliness stigma, as well as the intergenerational transmission of the two. Specifically, the study analyzed the effects of fathers’ and mothers’ regulatory focus on their own and their spouses’ stigma of loneliness. In addition, a mediation model was constructed to explore how parents’ regulatory focus influences their children’s stigma of loneliness and the potential mediating mechanisms involved.

Methods

Questionnaires were distributed to 470 college students and their parents, employing the Regulatory Focus Questionnaire (RFQ) and the Stigma of Loneliness Scale (SLS) to collect data.

Results

The analysis of intergenerational transmission effects revealed that parents’ regulatory focus and loneliness stigma significantly and positively predicted children’s regulatory focus and loneliness stigma, respectively. The Actor-Partner Interdependence Model (APIM) elucidated that both fathers’ and mothers’ promotion focus exerted significant influence on both actor and partner’s loneliness stigma. Furthermore, the mediation model analysis indicated that parents’ loneliness stigma, along with children’s regulatory focus operate as mediators in the influence of parental regulatory focus on loneliness stigma of their college-aged offspring.

Conclusions

From a familial context, this study, investigated the association between regulatory focus and loneliness stigma, along with the mediating roles within parent-child groups and couples. The findings enhanced our comprehension of the interrelation between regulatory focus and loneliness stigma, underpinned by empirical evidence.
The association between adipokines and pulmonary diseases: a mendelian randomization study
Authors: Wu Dongcai , Wang Ziyuan , Wang Keju , Wang Yuhan , Wang Tan
Published: January 2024

Background

The role of adipokines in the development of lung diseases is significant, yet their specific relationship with different lung diseases remains unclear.

Methods

In our research, we analyzed genetic variations associated with adipokines and various lung conditions such as interstitial lung disease, chronic obstructive pulmonary disease, asthma, lung cancer, sleep apnea, pneumonia, and tuberculosis, using data from public genome-wide studies. We employed Mendelian randomization techniques, including inverse variance weighting, weighted median, and MR-Egger regression methods, and conducted sensitivity checks to validate our findings.

Results

A study using the FinnGen database, which included 198,955 participants, identified 13 SNPs associated with adiponectin. Notably, adiponectin was found to significantly reduce the risk of interstitial lung disease and idiopathic pulmonary fibrosis. However, little evidence was found to establish a direct cause-effect relationship between the six adipokines and several other lung conditions, including sarcoidosis, asthma, chronic obstructive pulmonary disease, lung cancer, tuberculosis, pneumonia, and sleep apnea syndrome.

Conclusion

This study reveals a reverse link between adiponectin levels and the likelihood of interstitial lung disease, including idiopathic pulmonary fibrosis.
What affects the selection of diverting ileostomy in rectal cancer surgery: a single-center retrospective study
Authors: Wang Zhen , Guo Yuchen , Li Shuang , He Liang , Zhao Yinquan , Wang Quan
Published: January 2024

Background

The selection of diverting ileostomy (DI) is controversial. This study aimed to explore the factors affecting the selection of diverting ileostomy (DI) following laparoscopic low anterior resection for rectal cancer.

Methods

This retrospective, case-control study included patients who underwent laparoscopic-assisted sphincter-saving surgery for mid-low rectal cancer from January 2019 to June 2021. Univariate and multivariate analyses were performed on the patient’s clinicopathological characteristics and pelvic dimensions measured by abdominopelvic electron beam computed tomography.

Results

A total of 382 patients were included in the analysis, of which 182 patients (47.6%) did not undergo DI, and 200 patients (52.4%) underwent DI. The univariate analysis suggested that male sex (p = 0.003), preoperative radiotherapy (p < 0.001), patients with an anastomosis below the levator ani plane (p < 0.001), the intertuberous distance (p < 0.001), the sacrococcygeal distance (p = 0.025), the mid pelvis anteroposterior diameter (p = 0.009), and the interspinous distance (p < 0.001) were associated with performing DI. Multivariate analysis confirmed that preoperative radiotherapy (p = 0.037, odds ratio [OR] = 2.98, 95% confidence interval [CI] = 1.07–8.30), anastomosis below the levator ani plane (p < 0.001, OR = 7.09, 95% CI = 4.13–12.18), and the interspinous distance (p = 0.047, OR = 0.97, 95% CI = 0.93-1.00) were independently associated with performing DI.

Conclusion

Pelvic parameters also influence the choice of DI. According to this single-center experience, patients with a shorter interspinous distance, particularly narrow pelvic with an interspinous distance of < 94.8 mm, preoperative radiotherapy, and anastomosis below the levator ani plane, prefer to have a DI and should be adequately prepared by the physician.
Etiology, consequences, and solutions of working women’s work-life conflict: a qualitative study
Authors: Hosseini Zahra , Rahimi Seyyede Fateme , Salmani Fatemeh , Miri Mohammad Reza , Aghamolaei Teamur , Dastjerdi Reza
Published: January 2024

Introduction

Work-life conflict (WLC) is important in organizational behavior research and human resource management. The present research aimed to investigate the underlying causes, consequences, and solutions to WLC in Iranian working women.

Materials and methods

The present qualitative study was conducted through a content analysis method among 19 working married women in Birjand, a city in the east of Iran, from December 2021 to February 2022. To collect the data, semi-structured interviews were held. The average interview time was 45 minutes, and all interviews were recorded upon the participants’ consent. Finally, after coding, the information was analyzed with MAXQDA software.

Findings

The causes of conflict included 4 main categories of individual, interpersonal, organizational, and cultural factors, with seven subcategories: the pressure of the mother’s role at home, personality traits, lack of individual skills, insufficient support, work characteristics, organizational policies, and the traditional role of women in society.

The consequences of conflict included 2 main categories, Decreasing quality of life and work problems with 4 subcategories: physical and mental illnesses, forgetting one’s role towards others, limiting social communication, and reducing productivity.

Conflict resolution methods included 3 main classes of individual-oriented, other-oriented, and organization-oriented with 8 subclasses: program-oriented, meaning-oriented, emotion-oriented, avoidance, emotional support, instrumental and work support, support work policies, and correct management views.

Conclusion

To solve the problem of conflict, different aspects should be considered and help to solve this challenge by influencing each dimension.
Machine learning to predict unintended pregnancy among reproductive-age women in Ethiopia: evidence from EDHS 2016
Authors: Mamo Daniel Niguse , Gebremariam Yosef Haile , Adem Jibril Beshir , Kebede Shimels Derso , Walle Agmasie Damtew
Published: January 2024

Background

An unintended pregnancy is a pregnancy that is either unwanted or mistimed, such as when it occurs earlier than desired. It is one of the most important issues the public health system is currently facing, and it comes at a significant cost to society both economically and socially. The burden of an undesired pregnancy still weighs heavily on Ethiopia. The purpose of this study was to assess the effectiveness of machine learning algorithms in predicting unintended pregnancy in Ethiopia and to identify the key predictors.

Method

Machine learning techniques were used in the study to analyze secondary data from the 2016 Ethiopian Demographic and Health Survey. To predict and identify significant determinants of unintended pregnancy using Python software, six machine-learning algorithms were applied to a total sample of 7193 women. The top unplanned pregnancy predictors were chosen using the feature importance technique. The effectiveness of such models was evaluated using sensitivity, specificity, accuracy, and area under the curve.

Result

The ExtraTrees classifier was chosen as the top machine learning model after various performance evaluations. The region, the ideal number of children, religion, wealth index, age at first sex, husband education, refusal sex, total births, age at first birth, and mother’s educational status are identified as contributing factors in that predict unintended pregnancy.

Conclusion

The ExtraTrees machine learning model has a better predictive performance for identifying predictors of unintended pregnancies among the chosen algorithms and could improve with better policy decision-making in this area. Using these important features to help direct appropriate policy can significantly increase the chances of mother survival.
Mitigation of intrahepatic cholestasis induced by 17α-ethinylestradiol via nanoformulation of Silybum marianum L.
Authors: Salem Maha B. , Mohammed Dina Mostafa , Hammam Olfat A. , Elzallat Mohamed
Published: January 2024

Background

Cholestasis is an important predisposing factor for hepatocyte damage, liver fibrosis, primary biliary cirrhosis, and even liver failure. Silybum marianum L. (SM) plant is used in teas or eaten in some countries due to its antioxidant and hepatoprotective properties. Because of its low and poor oral bioavailability, so we improve the therapeutic activity of Silybum marianum L. extract (SM) by studying the potential effects of nanoformulation of Silybum marianium L. extract (nano-SM) on 17α-ethinylestradiol (EE)-induced intrahepatic cholestasis.

Methods

Thirty female Sprague-Dawley rats were divided into 5 groups (6 rats/group). Group I: Rats were received the treatment vehicle and served as normal group. Group II:Rats were injected daily with EE (10 mg/kg) for five successive days. Group III-V: Rats were injected daily with EE (10 mg/kg) and treated with either Ursodeoxycholic acid (UDCA) (40 mg/kg), SM (100 mg/kg) and nano-SM (100 mg/kg) orally once/day throughout the trialfor five successive days, respectively.

Results

Nano-SM greatly dampened the increase in serum levels of total and direct bilirubin, alanine aminotransaminase, aspartate aminotransaminase, and alkaline phosphatase caused by EE. Furthermore, nano-SM increased the hepatic contents of reduced glutathione (GSH) and catalase (CAT) and also upregulated the relative hepatic gene expressions of Rho-kinase (ROCK-1), myosin light chain kinase (MLCK), and myosin phosphatase target subunit (MYPT1) compared to the EE-induced group. Administration of nano-SM reduced hepatic lipid peroxidation and downregulated the relative hepatic expressions of the nuclear factor-kappa B (NF-ҡB) and interleukin-1β (IL-1β). In addition, nano-SM improved the histopathological changes induced by EE.

Conclusion

Nano-SM possessed a superior effect over SM, which can be considered an effective protective modality against EE-induced cholestatic liver injury through its antioxidant, anti-inflammatory activities, and enhancing bile acid (BA) efflux.
The impact of public leadership on collaborative administration and public health delivery
Authors: Zia ud din Muhammad , Yuan yuan Xu , Ullah Khan Naqib , Estay Christophe
Published: January 2024

Background

This research depicts the linkage of public leadership on public health delivery (PHD) and collaborative administration. The research is also focused to examine the effect of public leadership on public health delivery through the intervening variable of collaborative administration by using both social information processing theory and collaboration theory.

Methods

This research is based on quantitative method. Data was collected from 464 public hospital administration in the context of Pakistan. This study evaluated data using SPSS, AMOS, and PROCESS Macro.

Results

Public leadership has a positive profound effect on public health delivery and collaborative administration, and that collaborative administration significantly promotes public health delivery. The outcomes also exposed that public leadership has substantial influence on public health delivery through intervening collaborative administration.

Conclusions

Whilst public leadership demonstrated positive outcomes on public health delivery and collaborative administration, there is a need for more rigor studies on collaborative governance leadership, collaborative ethics and collaborative norms in the public health service.
Development of preimplantation genetic testing for monogenic reference materials using next-generation sequencing
Authors: Zhao Weihua , Song Yanyan , Huang Chuanfeng , Xu Shan , Luo Qi , Yao Runsi , Sun Nan , Liang Bo , Fei Jia , Gao Fangfang , Huang Jie , Qu Shoufang
Published: January 2024

Objective

Preimplantation genetic testing for monogenic disorders (PGT-M) has been used for over 20 years to detect many serious genetic conditions. However, there is still a lack of reference materials (RMs) to validate the test performance during the development and quality control of PGT-M.

Method

Sixteen thalassemia cell lines from four thalassemia families were selected to establish the RMs. Each family consisted of parents with heterozygous mutations for α- and/or β-thalassemia and two children, at least one of whom carried a homozygous thalassemia mutation (proband). The RM panel consisted of 12 DNA samples (parents and probands in 4 families) and 4 simulated embryos (cell lines constructed from blood samples from the four nonproband children). Four accredited genetics laboratories that offer verification of thalassemia samples were invited to evaluate the performance of the RM panel. Furthermore, the stability of the RMs was determined by testing after freeze‒thaw cycles and long-term storage.

Results

PGT-M reference materials containing 12 genome DNA (gDNA) reference materials and 4 simulated embryo reference materials for thalassemia testing were successfully established. Next-generation sequencing was performed on the samples. The genotypes and haplotypes of all 16 PGT-M reference materials were concordant across the four labs, which used various testing workflows. These well-characterized PGT-M reference materials retained their stability even after 3 years of storage.

Conclusion

The establishment of PGT-M reference materials for thalassemia will help with the standardization and accuracy of PGT-M in clinical use.
Adipokines in atopic dermatitis: the link between obesity and atopic dermatitis
Authors: Zhang Shiyun , Zhang Bingjie , Liu Yuehua , Li Li
Published: January 2024

Atopic dermatitis (AD) is a chronic skin condition with intense pruritus, eczema, and dry skin. The recurrent intense pruritus and numerous complications in patients with AD can profoundly affect their quality of life. Obesity is one of its comorbidities that has been confirmed to be the hazard factor of AD and also worsen its severity. Nevertheless, the specific mechanisms that explain the connection between obesity and AD remain incompletely recognized. Recent studies have built hopes on various adipokines to explain this connection. Adipokines, which are disturbed by an obese state, may lead to immune system imbalances in people with AD and promote the development of the disease. This review focuses on the abnormal expression patterns of adipokines in patients with AD and their potential regulatory molecular mechanisms associated with AD. The connection between AD and obesity is elucidated through the involvement of adipokines. This conduces to the in-depth exploration of AD pathogenesis and provides a new perspective to develop therapeutic targets.
CD44-targeting hyaluronic acid-selenium nanoparticles boost functional recovery following spinal cord injury
Authors: Luo Wenqi , Li Yueying , Zhao Jianhui , Niu Renrui , Xiang Chunyu , Zhang Mingyu , Xiao Chunsheng , Liu Wanguo , Gu Rui
Published: January 2024

Background

Therapeutic strategies based on scavenging reactive oxygen species (ROS) and suppressing inflammatory cascades are effective in improving functional recovery after spinal cord injury (SCI). However, the lack of targeting nanoparticles (NPs) with powerful antioxidant and anti-inflammatory properties hampers the clinical translation of these strategies. Here, CD44-targeting hyaluronic acid-selenium (HA-Se) NPs were designed and prepared for scavenging ROS and suppressing inflammatory responses in the injured spinal cord, enhancing functional recovery.

Results

The HA-Se NPs were easily prepared through direct reduction of seleninic acid in the presence of HA. The obtained HA-Se NPs exhibited a remarkable capacity to eliminate free radicals and CD44 receptor-facilitated internalization by astrocytes. Moreover, the HA-Se NPs effectively mitigated the secretion of proinflammatory cytokines (such as IL-1β, TNF-α, and IL-6) by microglia cells (BV2) upon lipopolysaccharide-induced inflammation. In vivo experiments confirmed that HA-Se NPs could effectively accumulate within the lesion site through CD44 targeting. As a result, HA-Se NPs demonstrated superior protection of axons and neurons within the injury site, leading to enhanced functional recovery in a rat model of SCI.

Conclusions

These results highlight the potential of CD44-targeting HA-Se NPs for SCI treatment.
“Naloxone? Not for me!” First cross-assessment by patients and healthcare professionals of the risk of opioid overdose
Authors: Aquizerate Aurélie , Rousselet Morgane , Cochard Axel , Guerlais Marylène , Gerardin Marie , Lefebvre Emilie , Duval Mélanie , Laforgue Edouard-Jules , Victorri-Vigneau Caroline
Published: January 2024

Background

Opioid-related mortality is a rising public health concern in France, where opioids were in 2021 implicated in 75% of overdose deaths. Opioid substitution treatment (OST) was implicated in almost half of deaths related to substance and drug abuse. Although naloxone could prevent 80% of these deaths, there are a number of barriers to the distribution of take-home naloxone (THN) among opioid users in France. This study is the first one which compares patients' self-assessment of the risk of future opioid overdose with the hetero-assessment provided by healthcare professionals in a population of individuals eligible for naloxone.

Methods

This was a multicenter descriptive observational study carried out in pharmacies across the Pays de la Loire region (France) during April and May 2022. All adult patients who visited a participating pharmacy for a prescription of OST and provided oral informed consent were enrolled in the study. Retrospective data were collected through cross-sectional interviews conducted by the pharmacist with the patient, utilizing an ad hoc questionnaire. The patient’s self-assessment of overdose risk was evaluated using a Likert scale from 0 to 10. The pharmacist relied on the presence or absence of overdose risk situations defined by the French Health Authority (HAS). The need to hold THN was assessed using a composite criterion.

Results

A total of 34 patients were interviewed; near one third were aware of the existence of THN and a minority had THN in their possession. Out of the 34 participants, 29 assessed their own risk of future opioid overdose: 65.5% reported having zero risk, while 6.9% believed they had a high risk. Nevertheless, at least one risk situation of opioid overdose was identified according to HAS criteria in 73.5% of the participants (n = 25). Consequently, 55% of the participants underestimated their risk of experiencing a future opioid overdose. Yet, dispensing THN has been judged necessary for 88.2% of the participants.

Conclusion

This study underscored the imperative need to inform not only healthcare professionals but also the patients and users themselves on the availability of THN and the risk situations of opioid overdose.
Immune characteristics of dedifferentiated retroperitoneal liposarcomas and the reliability of regional samples in evaluating their tumor immune microenvironments
Authors: Zhou Changsheng , Li Ming , Ren Yantao , Miao Fenglin , Wang Yue , Wu Ting , Gou Xin , Li Wengang
Published: January 2024

Background

Tumor immunotherapy is a new treatment breakthrough for retroperitoneal liposarcoma (RPLS), which is highly invasive and has few effective treatment options other than tumor resection. However, the heterogeneity of the tumor immune microenvironment (TIME) leads to missed clinical diagnosis and inappropriate treatment. Therefore, it is crucial to evaluate whether the TIME of a certain part of the tumor reliably represents the whole tumor, particularly for very large tumors, such as RPLS.

Methods

We conducted a prospective study to evaluate the TIME in different regions of dedifferentiated RPLS (DDRPLS) by detecting the expressions of markers such as CD4+, CD8+, Foxp3+, CD20+, CD68+, LAMP3+, PD-1+ tumor-infiltrating lymphocytes (TILs), and PD-L1 in tumors and corresponding paratumor tissues via immunohistochemistry and RNA sequencing.

Results

In DDRPLS, very few TILs were observed. Differentially expressed genes were significantly enriched in cell part and cell functions, as well as the metabolic pathway and PI3K-Akt signaling pathway. In addition, for most tumors (70–80%), the TIME was similar in different tumor regions.

Conclusions

For most tumors (70–80%), the TIME in any region of the tumor reliably represents the whole tumor. DDRPLS may regulate cell functions by modulating the metabolic and PI3K-Akt signaling pathways to promote its malignant behavior.
Patients with high nuclear grade pT1-ccRCC are more suitable for radical nephrectomy than partial nephrectomy: a multicenter retrospective study using propensity score
Authors: Xu Haozhe , Xing Zhuo , Ai Kai , Wang Jie , Lv Zhengtong , Deng Haitao , Li Ke , Wang Yang , Li Yuan
Published: January 2024

Background

Partial nephrectomy (PN) is usually recommended for T1 stage clear cell renal cell carcinoma (ccRCC) regardless of the nuclear grades. However, the question remains unresolved as to whether PN is non-inferior to RN in patients with T1-ccRCC at higher risk of recurrence. In fact, we found that patients with high nuclear grades treated with PN had poorer prognosis compared with those treated with radical nephrectomy (RN). Therefore, this study was designed to evaluate the associations of PN and RN in the four nuclear grade subsets with oncologic outcomes.

Methods

A retrospective study was conducted in three Chinese urological centers that included 1,714 patients who underwent PN or RN for sporadic, unilateral, pT1, N0, and M0 ccRCC without positive surgical margins and neoadjuvant therapy between 2010 and 2019. Associations of nephrectomy type with local ipsilateral recurrence, distant metastases, and all-cause mortality (ACM) were evaluated using the Kaplan–Meier method and multivariable Cox proportional hazards regression models after overlap weighting (OW).

Results

A total of 1675 patients entered the OW cohort. After OW, in comparison to PN, RN associated with a reduced risk of local ipsilateral recurrence in the G2 subset (HR = 0.148, 95% CI 0.046–0.474; p < 0.05), G3 subset (HR = 0.097, 95% CI 0.021–0.455; p < 0.05), and G4 subset (HR = 0.091, 95% CI 0.011–0.736; p < 0.05), and resulting in increased five-year local recurrence-free survival rates of 7.0%, 17.9%, and 36.2%, respectively. An association between RN and a reduced risk of distant metastases in the G4 subset (HR = 0.071, 95% CI 0.016–0.325; p < 0.05), with the five-year distant metastases-free survival rate increasing by 33.1% was also observed. No significant difference in ACM between PN and RN was identified.

Conclusions

Our findings substantiate that opting for RN, as opposed to PN, is more advantageous for local recurrence-free survival and distant metastases-free survival in patients with high nuclear grade (especially G4) pT1-ccRCC. We recommend placing a heightened emphasis on enhancing preoperative nuclear grade assessment, as it can significantly influence the choice of surgical plan.

Trial registration

This study was registered at Chinese Clinical Trial Registry (ID: ChiCTR2200063333).
What can we learn from general practitioners who left Spain? A mixed methods international study
Authors: Calderón-Larrañaga Sara , González-De-La-Fuente Ángel , Espinosa-González Ana Belén , Casado-Vicente Verónica , Brito-Fernandes Óscar , Klazinga Niek , Kringos Dionne
Published: January 2024

Background

International mobility of health workforce affects the performance of health systems and has major relevance in human resources for health policy and planning. To date, there has been little research exploring the reasons why general practitioners (GPs) migrate. This mixed methods study aimed to investigate the reasons why Spain-trained GPs migrate and develop GP retention and recruitment health policy recommendations relevant to Spanish primary care.

Methods

The study followed an explanatory sequential mixed methods study design combining surveys with semi-structured interviews and focus groups with GPs who qualified in Spain and were living overseas at the time of the study. The survey data examined the reasons why GPs left Spain and their intention to return and were analysed using quantitative methods. The transcripts from interviews and focus groups centred on GPs’ insights to enhance retention and recruitment in Spain and were analysed thematically.

Results

The survey had 158 respondents with an estimated 25.4% response rate. Insufficient salary (75.3%), job insecurity and temporality (67.7%), excessive workload (67.7%), poor primary care governance (55.7%), lack of flexibility in the workplace (43.7%) and personal circumstances (43.7%) were the main reasons for leaving Spain. Almost half of the respondents (48.7%) would consider returning to Spanish general practice if their working conditions improved. Interviews and focus groups with respondents (n = 24) pointed towards the need to improve the quality of employment contracts, working conditions, opportunities for professional development, and governance in primary care for effective retention and recruitment.

Conclusion

Efforts to improve GP retention and recruitment in Spain should focus on salary, job security, flexibility, protected workload, professional development, and governance. We draw ten GP retention and recruitment recommendations expected to inform urgent policy action to tackle existing and predicted GP shortages in Spanish primary care.
Fibronectin mediates activin A-promoted human trophoblast migration and acquisition of endothelial-like phenotype
Authors: Lan Xiangxin , Guo Ling , Hu Cuiping , Zhang Qian , Deng Jianye , Wang Yufeng , Chen Zi-Jiang , Yan Junhao , Li Yan
Published: January 2024

Background

During human early placentation, a proportion of extravillous trophoblasts (EVTs) migrate to the maternal decidua, differentiating into endovascular EVTs to remodel spiral arteries and ensure the establishment of blood circulation at the maternal-fetal interface. Inadequate EVT migration and endovascular differentiation are closely associated with adverse pregnancy outcomes such as miscarriage. Activin A and fibronectin are both secretory molecules abundantly expressed at the maternal-fetal interface. Activin A has been reported to regulate EVT biological functions. However, whether fibronectin mediates activin A-promoted EVT migration and acquisition of endothelial-like phenotype as well as the underlying molecular mechanisms remain unknown. Additionally, the role of fibronectin in pregnancy establishment and maintenance warrants further investigation.

Methods

Primary and immortalized (HTR8/SVneo) human EVTs were used as in vitro study models. Cultured human first-trimester chorionic villous explants were utilized for ex vivo validation. A local fibronectin knockdown model in ICR mouse uteri, achieved by nonviral in vivo transfection with small interfering RNA (siRNA) targeting fibronectin 1 (si-Fn1), was employed to explore the roles of fibronectin in the establishment and maintenance of early pregnancy.

Results

Our results showed that activin A treatment significantly induced fibronectin 1 (FN1) mRNA expression and fibronectin protein production, which is essential for human trophoblast migration and endothelial-like tube formation. Both basal and activin A-upregulated fibronectin expression were abolished by the TGF-β type I receptor inhibitor SB431542 or siRNA-mediated knockdown of activin receptor-like kinase (ALK4) or SMAD4. Moreover, activin A-increased trophoblast migration and endothelial-like tube formation were attenuated following the depletion of fibronectin. Fibronectin knockdown via intrauterine siRNA administration reduced CD31 and cytokeratin 8 (CK8) expression at the maternal-fetal interface, resulting in a decrease in the number of implantation sites and embryos.

Conclusions

Our study demonstrates that activin A promotes trophoblast cell migration and acquisition of endothelial-like phenotype via ALK4-SMAD2/3-SMAD4-mediated fibronectin upregulation. Furthermore, through a local fibronectin knockdown model in mouse uteri, we found that the absence of fibronectin at the maternal-fetal interface impedes endovascular migration of trophoblasts and decidual vascularization, thereby interfering with early embryo implantation and the maintenance of pregnancy. These findings provide novel insights into placental development during early pregnancy establishment and contribute to the advancement of therapeutic approaches for managing pregnancy complications related to trophoblast dysfunction.
Emerging applications of single-cell profiling in precision medicine of atherosclerosis
Authors: Lin Huiling , Zhang Ming , Hu Mi , Zhang Yangkai , Jiang WeiWei , Tang Wanying , Ouyang Yuxin , Jiang Liping , Mi Yali , Chen Zhi , He Pingping , Zhao Guojun , Ouyang Xinping
Published: January 2024

Atherosclerosis is a chronic, progressive, inflammatory disease that occurs in the arterial wall. Despite recent advancements in treatment aimed at improving efficacy and prolonging survival, atherosclerosis remains largely incurable. In this review, we discuss emerging single-cell sequencing techniques and their novel insights into atherosclerosis. We provide examples of single-cell profiling studies that reveal phenotypic characteristics of atherosclerosis plaques, blood, liver, and the intestinal tract. Additionally, we highlight the potential clinical applications of single-cell analysis and propose that combining this approach with other techniques can facilitate early diagnosis and treatment, leading to more accurate medical interventions.
Hypoxia upregulating ACSS2 enhances lipid metabolism reprogramming through HMGCS1 mediated PI3K/AKT/mTOR pathway to promote the progression of pancreatic neuroendocrine neoplasms
Authors: Gu Danyang , Ye Mujie , Zhu Guoqin , Bai Jianan , Chen Jinhao , Yan Lijun , Yu Ping , Lu Feiyu , Hu Chunhua , Zhong Yuan , Liu Pengfei , He Qibin , Tang Qiyun
Published: January 2024

Background

Pancreatic neuroendocrine neoplasms (pNENs) are relatively rare. Hypoxia and lipid metabolism-related gene acetyl-CoA synthetase 2 (ACSS2) is involved in tumor progression, but its role in pNENs is not revealed. This study showed that hypoxia can upregulate ACSS2, which plays an important role in the occurrence and development of pNENs through lipid metabolism reprogramming. However, the precise role and mechanisms of ACSS2 in pNENs remain unknown.

Methods

mRNA and protein levels of ACSS2 and 3-hydroxy-3-methylglutaryl-CoA synthase1 (HMGCS1) were detected using quantitative real-time PCR (qRT-PCR) and Western blotting (WB). The effects of ACSS2 and HMGCS1 on cell proliferation were examined using CCK-8, colony formation assay and EdU assay, and their effects on cell migration and invasion were examined using transwell assay. The interaction between ACSS2 and HMGCS1 was verified by Co-immunoprecipitation (Co-IP) experiments, and the functions of ACSS2 and HMGCS1 in vivo were determined by nude mouse xenografts.

Results

We demonstrated that hypoxia can upregulate ACSS2 while hypoxia also promoted the progression of pNENs. ACSS2 was significantly upregulated in pNENs, and overexpression of ACSS2 promoted the progression of pNENs and knockdown of ACSS2 and ACSS2 inhibitor (ACSS2i) treatment inhibited the progression of pNENs. ACSS2 regulated lipid reprogramming and the PI3K/AKT/mTOR pathway in pNENs, and ACSS2 regulated lipid metabolism reprogramming through the PI3K/AKT/mTOR pathway. Co-IP experiments indicated that HMGCS1 interacted with ACSS2 in pNENs. Overexpression of HMGCS1 can reverse the enhanced lipid metabolism reprogramming and tumor-promoting effects of knockdown of ACSS2. Moreover, overexpression of HMGCS1 reversed the inhibitory effect of knockdown of ACSS2 on the PI3K/AKT/mTOR pathway.

Conclusion

Our study revealed that hypoxia can upregulate the lipid metabolism-related gene ACSS2, which plays a tumorigenic effect by regulating lipid metabolism through activating the PI3K/AKT/mTOR pathway. In addition, HMGCS1 can reverse the oncogenic effects of ACSS2, providing a new option for therapeutic strategy.