bluuebunny/crossref_metadata_2025 huggingface dataset:
Review of Strategies and Policies for Enhanced Participation in Global Value Chains
Authors: Dutta Sourish
Published: July 2024

This article underscores the immense potential for substantial economic growth and development that can be harnessed through effective participation in global value chains (GVCs). It emphasises the role of policymakers in adeptly navigating GVCs, prioritising tasks, exploring different forms of GVC governance, and fostering a conducive environment for foreign investments. By effectively managing power dynamics and supply chain risks, countries can attract valuable foreign investors, enhance market connectivity, and improve infrastructure and services, leading to significant economic growth. The potential benefits of GVC participation are vast, and policymakers can shape the situation by understanding and addressing strategic inquiries, laying the foundation for a prosperous future. Furthermore, the article explores the potential for a country to enhance its involvement in GVCs and progress to more lucrative activities by strengthening existing connections between GVCs and the local economy. By enhancing the capacity of local stakeholders to acquire knowledge, policymakers can play a crucial role in maximising the benefits from GVC spillovers, positively impacting a country's economic development.
Some remarks on the argument appealing to nature against synthetic biology
Authors: Lei Ruipeng , Peng Yifan , He Yutian , Li Jun
Published: July 2024

This paper will focus on analyzing the argument with appealing to nature against synthetic biology and provide a counter-argument against it through demonstrating the ambiguity of the concept of nature, denying the existence of a morally significant line between natural and non/unnatural, and disproving the allegations against synthetic biology raised by the argument appealing to nature. The paper consists of two parts following a brief introduction. The first part will describe the argument appealing to nature against synthetic biology, and identify the deficiencies of the argument per se, e.g., the ambiguity of the concept ‘nature’; and the problems in the morally significant line between the natural and the non/unnatural. The second part will discuss the allegations to synthetic biology stemming from this argument, e.g., committing metaphysical and ethical mistakes, and doing possible harms to the environment.
A review on over-sampling techniques in classification of multi-class imbalanced datasets: insights for medical problems
Authors: Yang Yuxuan , Khorshidi Hadi Akbarzadeh , Aickelin Uwe
Published: July 2024

There has been growing attention to multi-class classification problems, particularly those challenges of imbalanced class distributions. To address these challenges, various strategies, including data-level re-sampling treatment and ensemble methods, have been introduced to bolster the performance of predictive models and Artificial Intelligence (AI) algorithms in scenarios where excessive level of imbalance is present. While most research and algorithm development have been focused on binary classification problems, in health informatics there is an increased interest in the field to address the problem of multi-class classification in imbalanced datasets. Multi-class imbalance problems bring forth more complex challenges, as a delicate approach is required to generate synthetic data and simultaneously maintain the relationship between the multiple classes. The aim of this review paper is to examine over-sampling methods tailored for medical and other datasets with multi-class imbalance. Out of 2,076 peer-reviewed papers identified through searches, 197 eligible papers were chosen and thoroughly reviewed for inclusion, narrowing to 37 studies being selected for in-depth analysis. These studies are categorised into four categories: metric, adaptive, structure-based, and hybrid approaches. The most significant finding is the emerging trend toward hybrid resampling methods that combine the strengths of various techniques to effectively address the problem of imbalanced data. This paper provides an extensive analysis of each selected study, discusses their findings, and outlines directions for future research.
Causal effects of plasma metabolites on chronic kidney diseases and renal function: a bidirectional Mendelian randomization study
Authors: Zhao Xiaodong , Gao Jialin , Kou Kai , Wang Xi , Gao Xin , Wang Yishu , Zhou Honglan , Li Faping
Published: July 2024

Background

Despite the potential demonstrated by targeted plasma metabolite modulators in halting the progression of chronic kidney disease (CKD), a lingering uncertainty persists concerning the causal relationship between distinct plasma metabolites and the onset and progression of CKD.

Methods

A genome-wide association study was conducted on 1,091 metabolites and 309 metabolite ratios derived from a cohort of 8,299 unrelated individuals of European descent. Employing a bidirectional two-sample Mendelian randomization (MR) analysis in conjunction with colocalization analysis, we systematically investigated the associations between these metabolites and three phenotypes: CKD, creatinine-estimated glomerular filtration rate (creatinine-eGFR), and urine albumin creatinine ratio (UACR). In the MR analysis, the primary analytical approach employed was inverse variance weighting (IVW), and sensitivity analysis was executed utilizing the MR-Egger method and MR-pleiotropy residual sum and outlier (MR-PRESSO). Heterogeneity was carefully evaluated through Cochrane’s Q test. To ensure the robustness of our MR results, the leave-one-out method was implemented, and the strength of causal relationships was subjected to scrutiny via Bonferroni correction.

Results

Our thorough MR analysis involving 1,400 plasma metabolites and three clinical phenotypes yielded a discerning identification of 21 plasma metabolites significantly associated with diverse outcomes. Specifically, in the forward MR analysis, 6 plasma metabolites were determined to be causally associated with CKD, 16 with creatinine-eGFR, and 7 with UACR. Substantiated by robust evidence from colocalization analysis, 6 plasma metabolites shared causal variants with CKD, 16 with creatinine-eGFR, and 7 with UACR. In the reverse analysis, a diminished creatinine-eGFR was linked to elevated levels of nine plasma metabolites. Notably, no discernible associations were observed between other plasma metabolites and CKD, creatinine-eGFR, and UACR. Importantly, our analysis detected no evidence of horizontal pleiotropy.

Conclusion

This study elucidates specific plasma metabolites causally associated with CKD and renal functions, providing potential targets for intervention. These findings contribute to an enriched understanding of the genetic underpinnings of CKD and renal functions, paving the way for precision medicine applications and therapeutic strategies aimed at impeding disease progression.
Mechanism and application of fibrous proteins in diabetic wound healing: a literature review
Authors: Yan Lilin , Wang Yuqing , Feng Jiawei , Ni Yiming , Zhang Ting , Cao Yemin , Zhou Mingmei , Zhao Cheng
Published: July 2024

Diabetic wounds are more complex than normal chronic wounds because of factors such as hypoxia, reduced local angiogenesis, and prolonged inflammation phase. Fibrous proteins, including collagen, fibrin, laminin, fibronectin, elastin etc., possess excellent inherent properties that make them highly advantageous in the area of wound healing. Accumulating evidence suggests that they contribute to the healing process of diabetic wounds by facilitating the repair and remodel of extracellular matrix, stimulating the development of vascular and granulation tissue, and so on. However, there is currently a lack of a comprehensive review of the application of these proteins in diabetes wounds. An overview of fibrous protein characteristics and the alterations linked to diabetic wounds is given in this article’s initial section. Next is a summary of the advanced applications of fibrous proteins in the last five years, including acellular dermal matrix, hydrogel, foam, scaffold, and electrospun nanofibrous membrane. These dressings have the ability to actively promote healing in addition to just covering wounds compared to traditional wound dressings like gauze or bandage. Research on fibrous proteins and their role in diabetic wound healing may result in novel therapeutic modalities that lower the incidence of diabetic wounds and thereby enhance the health of diabetic patients.
Heat transfer and system performance of a novel solar ground-source heat-pump system with borehole heat exchangers using a combined parallel and series connection
Authors: Wu Chunling , Song Mengyao , Jin Lu , Fu Qiang , Zhu Longhu
Published: July 2024

A novel BHEs is proposed that can overcome the problems associated with the low heat-transfer efficiency of borehole heat exchangers (BHEs) that are connected in series (BHEs-S) and the low heat-transfer temperature differences of BHEs that are connected in parallel (BHEs-P). The new BHE uses a combined series and parallel connection (BHEs-CSP), which can further be classified into individual in-series and in-parallel zones. A numerical model of the new BHEs-CSP is then developed to optimize the key design parameters such as borehole spacing, number of series stages, and heat-extraction methods. The results show that, with the optimal configuration, the average soil temperature with a BHEs-CSP is 6.70°C higher than for a BHE that is connected in parallel. Furthermore, the heat-transfer efficiency can be improved by 4.1% compared to BHEs that are connected in series. It is recommended that the distance between buried pipes in the series area and parallel area should be 5.25 m, and the series number of buried pipe groups should be 4. To study the overall performance of the solar-assisted ground-source heat-pump with a BHEs-CSP (SAGSHP-CSP), a TRNSYS model is developed. The results show that the optimal area- and heat-storage-ratios (for in-series zone to in-parallel zone), using SAGSHP-CSP, are 1:4 and 3:2, respectively. Under these conditions, the system coefficient of performance (SCOP) is over 5.2 and the COP and SCOP is improved by 9.8% and 13.0% compared to GSHP systems with BHEs-P. Furthermore, an improvement by 18.4% and 18.2%, compared to the GSHP system with BHEs-S, is reported.
Practicalities of community-led continuous water quality monitoring: lessons from Taiwan and UK pilots
Authors: Starkey Eleanor , Jones Amy , Ochoa-Rodriguez Susana , Mahajan Sachit , Wei Chi-Ling , Chen Pei-Chun , Liu Shau-Yuan , Wang Li-Pen , Walsh Claire L.
Published: July 2024

Freshwater pollution is a global challenge that citizens recognise as unacceptable, despite professional efforts to monitor, manage, and regulate it. Water quality is difficult to observe at high spatial and temporal resolutions; it is costly and typically requires trained specialists in the field and in laboratories. However, the rise in citizen science monitoring has generated opportunities to overcome many barriers and fill data gaps. Citizens want access to actionable water quality information that can provide early warnings and drive change. Our bibliographic analysis emphasises that citizen science is rarely paired with the use of continuous sensors, and many monitoring schemes involving the public are unable to offer the detail required. This study has explored the practicalities and competencies associated with community-led (near) continuous water quality monitoring (CWQM), and has generated an extensive checklist containing technical, social, economic, and wider responsibilities that stakeholders should consider. The “UpStream” project has provided a testbed for this exploratory work and the development and deployment of the “WaterBox” CWQM device. Case studies from the UK and Taiwan, where community-led CWQM programmes have been piloted, have provided novel methodological insights. Lessons learnt have enabled researchers to determine whether, and to what extent, community-led CWQM is achievable in practice. Results confirm that 75% of the practicalities observed fall under the “technical” category, despite offering a social and inclusive methodology. Through observational work, it was found that only 34% of the 104 practicalities were led by community groups and community champions. Communities require significant support owing to the sheer number of technical barriers, although some of this could be provided by skilled community champions. These findings have surfaced despite the WaterBox equipment being open, accessible, cost-effective, and adaptable. Unless support is in place and/or technology significantly evolves to reduce the number of challenges, it is unlikely that communities will lead and take full ownership of CWQM programmes. Despite this, the generation of site-specific CWQM data are welcomed by citizens, who can co-design schemes, interpret trends and offer valuable local information that trained scientists cannot achieve alone. These transferable findings are relevant to monitoring initiatives across the environmental sector.
How to maintain environmental integrity when using state support and the VCM to co-finance BECCS projects - a Swedish case study
Authors: Dufour Malin , Möllersten Kenneth , Zetterberg Lars
Published: July 2024

Limiting global warming to close to 1.5°C by 2100 requires deep and rapid greenhouse gas emission reductions and carbon dioxide removals (CDR) on a massive scale, presenting a remarkable scaling challenge. This paper focuses on the financing of bioenergy with carbon capture and storage (BECCS) in Sweden. BECCS is one of the most prominent CDR methods in 1.5°C-compatible global emission scenarios and has been assigned a specific role in Swedish policy for net-zero. A Swedish state support system for BECCS based on results-based payments is planned. Furthermore, demand for CDR-based carbon credits is on the rise on the voluntary carbon markets (VCM) for use towards voluntary mitigation targets. Risks involved with the current Swedish policies are analysed, specifically for the co-financing of BECCS by the planned state support and revenues from the VCM. We find that with the current policies, state support systems will subsidise carbon credit prices on the VCM. We argue that such subsidisation can lower decarbonisation efforts by lowering the internal carbon price set by actors, thus undermining environmental integrity. It is concluded that proportional attribution should be applied, i.e., attributing mitigation outcomes to the state support and VCM revenue in proportion to their financial contribution to the CDR achieved. The attribution analysis should be accompanied by adjustments in national greenhouse gas accounting so that mitigation outcomes that are issued as carbon credits and used for offsetting are not double claimed (i.e., not used by both a nation and a non-state actor on the VCM towards their respective mitigation targets). If proportional attribution and adjustments in national GHG accounting are not implemented, the credibility and environmental integrity of offsetting claims made by carbon credit users are eroded. We recommend that action is taken to operationalise and implement proportional attribution to allow for co-financing of BECCS projects while maintaining environmental integrity. Wider implications for our recommendations beyond the case of Swedish BECCS are also analysed.
Sustainable growth unveiled: exploring the nexus of green finance and high-quality economic development in China
Authors: Xu Yige , Ding Zhao
Published: July 2024

Amidst global sustainability challenges, green finance emerges as a crucial instrument for advancing sustainable development, garnering increasing attention for its pivotal role in fostering high-quality economic development (HQED), particularly within the dynamic economic landscape of China. This study delves into the nexus between green finance and HQED across 30 Chinese provinces from 2012 to 2021. Employing the entropy method, indices for green finance and HQED index system are calculated, and their interaction is analyzed through a panel data model, incorporating tests for moderating effects of FinTech and green technological innovation, as well as assessing the heterogeneity across diverse regions. The findings highlight green finance’s significant role in enhancing HQED, with notable regional disparities. Specifically, the eastern region shows the strongest impact, followed by the central region, while the western and northeastern regions exhibit weaker influences. The study also identifies FinTech and green technological innovation as pivotal moderators, amplifying green finance’s positive effect on HQED. These insights underscore green finance’s importance in driving sustainable economic growth and highlight the necessity for region-specific strategies to optimize its impact. Policy recommendations based on these findings include prioritizing the development of green finance, formulating region-specific strategies, and leveraging the catalytic roles of FinTech and green technological innovation to enhance the efficacy of green finance in achieving HQED.
Diffusion of AI value-driven services in the German manufacturing industries—an empirical examination of value-driven service references classified by the business Model Canvas
Authors: Berger Patrick , von Garrel Joerg
Published: July 2024

This study investigates the diffusion of AI-based service applications within the business models of German manufacturing industries, surveying 162 decision-makers. The integration of AI into business model is assessed through the Business Model Canvas (BMC) framework, evaluating its value in terms of effectiveness as well as efficiency. Rather than focusing on specific use cases, the study delves into the intended usage of value-driven AI services references to enhance effectiveness and efficiency across various elements of the business models. Through this research, eleven service values have been identified. Each service vale corresponds to a distinct element of the BMC. Decision-makers were surveyed using a Confirmation/Disconfirmation (C/D) paradigm to measure the disparities between their current and target performance levels. Consequently, this study provides valuable insights from the perspective of decision makers regarding the current and desired state of AI integration in the German manufacturing industry, taking into account AI usage or no AI usage at the time of data collection.
Acquisition of anti-phosphatidylserine IgM and IgG antibodies by infants and their mothers over time in Uganda
Authors: Tijani Muyideen Kolapo , Saleh Bandar Hassan , Lugaajju Allan , Danielsson Lena , Persson Kristina E. M.
Published: July 2024

Background

Production of anti-phosphatidylserine (anti-PS) antibodies has been associated with malaria and can aggravate pathology. How these autoantibodies develop during early childhood in a malaria context is not known. We examined levels of anti-PS IgG and IgM antibodies in a longitudinal cohort of mother-baby pairs during birth, in the infants at 2.5, 6 months, and in mothers and their babies at 9 months postpartum.

Results

There was no difference between levels of anti-PS IgG in cord blood and the mothers’ peripheral blood at birth. However, anti-PS IgM levels were significantly higher in the mothers compared to the infants’ cord blood, and IgM levels were steadily increasing during the first 9 months of the infants’ life. In infants that had the highest anti-PS IgM levels at birth, there was a decline until 6 months with a rise at 9 months. Infants that possessed high anti-PS IgG at birth also exhibited a progressive decline in levels. When anti-PS were correlated to different fractions of B-cells, there were several correlations with P. falciparum specific atypical B cells both at birth and at 2.5 months for the infants, especially for anti-PS IgM. Anti-PS also correlated strongly to C1q-fixing antibodies at birth.

Conclusion

These results show that anti-PS IgG acquired by mothers could be transferred transplacentally and that IgM antibodies targeting PS are acquired during the first year of life. These results have increased the knowledge about autoimmune responses associated with infections in early life and is critical for a comprehensive understanding of malaria vaccine functionality in endemic areas.
The oral-gut microbiome axis in inflammatory bowel disease: from inside to insight
Authors: Wang Aili , Zhai Zihan , Ding Yiyun , Wei Jingge , Wei Zhiqiang , Cao Hailong
Published: July 2024

Inflammatory bowel disease (IBD) is an idiopathic and persistent inflammatory illness of the bowels, leading to a substantial burden on both society and patients due to its high incidence and recurrence. The pathogenesis of IBD is multifaceted, partly attributed to the imbalance of immune responses toward the gut microbiota. There is a correlation between the severity of the disease and the imbalance in the oral microbiota, which has been discovered in recent research highlighting the role of oral microbes in the development of IBD. In addition, various oral conditions, such as angular cheilitis and periodontitis, are common extraintestinal manifestations (EIMs) of IBD and are associated with the severity of colonic inflammation. However, it is still unclear exactly how the oral microbiota contributes to the pathogenesis of IBD. This review sheds light on the probable causal involvement of oral microbiota in intestinal inflammation by providing an overview of the evidence, developments, and future directions regarding the relationship between oral microbiota and IBD. Changes in the oral microbiota can serve as markers for IBD, aiding in early diagnosis and predicting disease progression. Promising advances in probiotic-mediated oral microbiome modification and antibiotic-targeted eradication of specific oral pathogens hold potential to prevent IBD recurrence.
Risk factor analysis and nomogram construction of postoperative complications for patients with locally advanced gastric cancer who received neoadjuvant immunotherapy and chemotherapy
Authors: Cui Hao , Zhang Sijin , Sun Linde , Yuan Zhen , Xu Qixuan , Gao Jingwang , Chen Lin , Cui Jianxin , Wei Bo
Published: July 2024

Introduction

The combination of neoadjuvant immunotherapy and chemotherapy (NICT) has become a common treatment regimen for locally advanced gastric cancer (LAGC). However, the safety and efficacy of radical gastrectomy following NICT (NICT-G) remain controversial. This study aimed to analyze the risk factors influencing postoperative complications (POCs) after NICT-G. Additionally, it aimed to construct a nomogram to provide a clinical reference for predicting POCs.

Methods

This study included 177 patients who received NICT-G at the Chinese PLA General Hospital First Medical Center from January 2020 to January 2024. Univariable and multivariable logistic regression models were used to evaluate the risk factors influencing POCs, and a nomogram model was constructed. To evaluate the discrimination and accuracy of the nomogram model, the area under the receiver operating characteristic curve (AUC) and the calibration curve were measured.

Results

In 177 patients who received NICT-G, the pathological complete response and major pathological response rates were 15.8% and 45.2%, respectively, whereas the rates of the overall and severe treatment-related adverse events were 71.8% and 15.8%, respectively. In addition, 43 (24.3%) patients developed overall POCs (Clavien–Dindo classification ≥ II). Univariable and multivariable logistic analyses showed that age ≥70 years, greater estimated blood loss, platelet/lymphocyte ratio (PLR) ≤196, neutrophil/lymphocyte ratio (NLR) >1.33, non-R0 resection, and body mass index (BMI) < 18.5 kg/m2 were independent risk factors for overall POCs (p < 0.05). The nomogram model developed using the abovementioned variables showed that the AUC (95% confidence interval [CI]) was 0.808 (95% CI): 0.731–0.885 in predicting the POC risk. The calibration curves showed that the prediction curve of the nomogram was a good fit for the actual POCs (Hosmer–Lemeshow test: χ2 = 5.76, P = 0.451).

Conclusion

The independent risk factors for overall POCs in the NICT-G were age ≥ 70 years, greater estimated blood loss, PLR ≤ 196, NLR > 1.33, non-R0 resection, and BMI < 18.5 kg/m2. The nomogram model developed based on the abovementioned indicators showed better accuracy in predicting the POC risk.
Effect of the health and wellness Kneipp concept on health promotion and reduction of sick days for kindergarten children: a cluster randomized controlled trial protocol
Authors: Gerganova Marinela , Schepanski Steven , Bogdanski Martin , Kandil Farid I. , Tekath Angela , Jeitler Michael , Stritter Wiebke , Blakeslee Sarah B. , Seifert Georg
Published: July 2024

Background

The holistic health and wellness Kneipp concept, has a long tradition in Europe with demonstrated health benefits. Based on the five elements of the Kneipp concept, kindergartens in and around Germany are used to certify “Kneipp Kindergartens” that practice regular Kneipp applications and activities: cold water applications, exercise, nutrition, herbs and mind-body interventions. Little is known about the potential health benefits for children, however. This study protocol describes our study design and intervention of the Kita Kneipp Study to investigate the effect of the Kneipp concept on kindergarten children aged 2–6 years.

Methods and design

The Kita Kneipp Study, registered with the German Clinical Trial Register (DRKS-ID: DRKS00029275), is a confirmatory, mixed-method, two-armed, waitlist, clinical, cluster randomized controlled trial (RCT). Kindergartens in Berlin, Germany that would like to implement the Kneipp concept into their facility will be recruited and randomized to the intervention or control group. Changes in the number of kindergarten sick days will be the primary outcome measure. Kindergarten attendance and reason for absence including illness will be collected on a weekly basis at two time points for 6 weeks from the parents and kindergarten directors: baseline and 1 year after baseline. Secondary outcomes will measure cold symptoms through the Common Cold Questionnaire (CCQ) and National Cancer Institute – Common Terminology Criteria for Adverse Events (NCI-CTCAE) Scales describing gastroenterological-based symptoms Kindergarten educator sick days will be aggregately reported for the same time period. Kneipp concept activities will be recorded on a weekly basis over the one-year intervention period. To understand the experience of Kneipp concept implementation and possible changes in the kindergarten, expert interviews will be conducted with intervention kindergarten educators and focused ethnographies will be planned to observe and analyze the intervention activities.

Discussion

This mixed method study design has potential to help identify if the Kneipp concept can be used for salutogenic purposes among young children and provide insights and experience of the implementation and practicing a holistic health and wellness concept in a kindergarten setting.
Age-specific disparity in insomnia among COVID-19 patients in Fangcang shelter hospitals: a population-based study in Shanghai, China
Authors: Shi Ruizi , Wang Yihui , Chen Ying , Yang Zhitao , Jing Feng , Shang Hanbing , Chen Erzhen , Zhou Ying
Published: July 2024

Background

Fangcang shelter hospitals are quarantine facilities offering primary medical treatment for mild and asymptomatic SARS-CoV-2 cases. Little is known about the age-specific prevalence of insomnia among patients in Fangcang shelter hospitals, particularly in older age groups.

Methods

This cross-sectional study was conducted in the three largest Fangcang shelter hospitals during the lockdown period, from March to May 2022, in Shanghai. The patients’ demographic and medical information was recorded. Insomnia was defined according to the prescriptions for zolpidem and estazolam. The overall and age-specific prevalence and the risk factors of insomnia were investigated through regression models.

Results

A total of 2,39,448 patients were included in this study (59.09% of the patients were male, the median age was 42, and 73.41% of the patients were asymptomatic), with the prevalence of insomnia being 3.1%. The prevalence of insomnia varied across different age groups (<18 years: 0.23%, 18–64 years: 2.64%, and ≥65 years: 10.36%). SARS-CoV-2 vaccine, regardless of the number of doses, was significantly associated with a decreased risk of insomnia for the group aged ≥65 years. Three doses of the vaccine reduced the risk of insomnia for patients aged 18–64 years. An extra day in the hospital significantly increased the risk of insomnia by approximately 10% for all age groups. Mild symptoms were significantly associated with a higher risk of insomnia among patients aged <65 years old, while being male and residing in the surrounding area were negatively associated with insomnia for all adults.

Conclusion

This study observed that older patients were a high-risk population for developing insomnia in Fangcang shelter hospitals. SARS-CoV-2 vaccination might decrease the risk of insomnia in adults, especially the older adult, which indicates the benefits of vaccination for reducing insomnia among infected patients.
The impact of inhalation versus total intravenous anesthesia on the immune status in patients undergoing breast cancer surgery: a double-blind randomized clinical trial (TeMP)
Authors: Kadantseva Kristina , Subbotin Valery , Akchulpanov Roman , Berikashvili Levan , Yadgarov Mikhail , Zhukova Lyudmila , Kvetenadze Guram , Svitich Oxana , Kukina Polina , Kuznetsov Ivan , Shemetova Mariya , Smirnova Anastasiya , Polyakov Petr , Shebankov Andrey , Likhvantsev Valery
Published: July 2024

Background

Breast cancer (BC) mortality primarily stems from metastases rather than the primary tumor itself. Perioperative stress, encompassing both surgical and anesthetic factors, profoundly impacts the immune system, leading to alterations in neuroendocrine pathways and immune functions, potentially facilitating tumor progression and metastasis. Understanding the immunomodulatory effects of different anesthesia techniques is crucial for optimizing perioperative care in patients with BC. The neutrophil-to-lymphocyte ratio (NLR) serves as one of the key indicators of perioperative immune response.

Objective

To compare the effects of inhalation anesthesia (IA) and total intravenous anesthesia (TIVA) on perioperative immune response in BC surgery patients.

Methods

In this randomized, double-blind clinical trial, BC surgery patients were randomized to receive either TIVA with propofol or IA with sevoflurane. The primary endpoint was NLR assessment. Secondary immune parameters measured included natural killer cells, various T cell subsets, B cells, the immuno-regulatory index [T-helpers (CD3+CD4+)/cytotoxic T-cells (CD3+CD8+)], matrix metallopeptidases (MMP-9), complement components, and immunoglobulins, preoperatively and at 1 and 24 hours postoperatively.

Results

The study included 98 patients (IA: 48, TIVA: 50). The baseline characteristics exhibited remarkable similarity across the groups. No significant difference in absolute NLR values was found between IA and TIVA groups at any time point (1 hour: p = 0.519, 24 hours: p = 0.333). Decreased IgA and IgM levels post-surgery suggested potential negative impacts of IA on humoral immunity compared to TIVA. CRP levels increased more by 24 hours (p = 0.044) in IA compared to TIVA. No significant differences were observed in natural killer cells, T cell subsets, B cells, MMP-9 levels or complement components between groups. Significant differences in the immuno-regulatory index between the TIVA and IA groups at one hour postoperatively (p = 0.033) were not maintained at 24 hours.

Conclusion

While there were no notable differences in NLR among the types of anesthesia, the observed disparities in immunoglobulin content and C-reactive protein levels between groups suggest that we cannot dismiss the potential immunosuppressive effects of inhalational anesthesia in breast cancer surgeries. Further investigation needed to clarify the impact of various anesthesia methods on immune function and their implications for long-term cancer outcomes.
Inflammatory markers as prognostic markers in patients with head and neck squamous cell carcinoma treated with immune checkpoint inhibitors: a systematic review and meta-analysis
Authors: Wang Quan , Yin Xiangzhi , Wang Shengxia , Lu Haijun
Published: July 2024

Background

Various inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein-to-albumin ratio (CAR), have been linked to the effectiveness of immunotherapy in multiple types of malignancies. We investigated how these inflammatory markers affect the prognosis of patients with head and neck squamous cell carcinoma (HNSCC) receiving immunotherapy.

Methods

The databases PubMed, Embase, and Cochrane were systematically searched up until March 26, 2024, to identify relevant literature. Hazard ratios (HR) and corresponding 95% confidence intervals (CI) were extracted from the eligible studies. Data analysis was conducted using Review Manager and STATA 17.0 software to assess the impact of each indicator on prognosis. Subgroup analysis was performed to explore potential sources of heterogeneity in the data.

Results

The analysis included sixteen studies with 1316 patients. A higher baseline NLR was significantly associated with poorer overall survival (OS) (pooled HR: 1.55, 95%CI: 1.14-2.11, P=0.006) and progression-free survival (PFS) (pooled HR: 1.59, 95% CI: 1.21-2.10, P<0.05). Furthermore, a high NLR after immunotherapy was strongly correlated with poor OS (pooled HR: 5.43, 95% CI: 3.63-8.12, P<0.01). Additionally, higher baseline C-reactive CAR was significantly associated with worse OS (pooled HR: 2.58, 95% CI: 1.96-3.40, P<0.01).

Conclusion

The inflammatory markers NLR and CAR serve as effective prognostic biomarkers for immunotherapy in patients with HNSCC. However, the practical application of clinical detection requires further validation through large-scale prospective studies to confirm these findings and explore the underlying mechanisms.
Laparoscopic pyeloplasty in neonates and infants is safe and efficient
Authors: Langreen S. , Ludwikowski B. , Dingemann J. , Ure B. M. , Hofmann A. D. , Kuebler J. F.
Published: July 2024

Introduction

Dismembered laparoscopic pyeloplasty (LP) is a well-accepted treatment modality for ureteropelvic junction obstruction (UPJO) in children. However, its efficacy and safety in infants, particularly neonates, remain uncertain. To address this significant knowledge gap, we aimed to compare outcomes between a cohort of neonates and infants undergoing LP vs. open pyeloplasty (OP) at less than 6 months and 6 weeks of age.

Material and methods

We conducted a retrospective analysis of data from patients who underwent primary pyeloplasty at our institution between 2000 and 2022. Only patients aged 6 months or less at the time of surgery were included, excluding redo-procedures or conversions. Ethical approval was obtained, and data were assessed for redo-pyeloplasty and postoperative complications, classified according to the Clavien–Madadi classification. A standard postoperative assessment was performed 6 weeks postoperatively. This included an isotope scan and a routine ultrasound up to the year 2020.

Results

A total of 91 eligible patients were identified, of which 49 underwent LP and 42 underwent OP. Patients receiving LP had a median age of 11.4 (1–25.4) weeks, compared to 13.8 (0.5–25.9) weeks for those receiving OP (p > 0.31). Both groups in our main cohort had an age range of 0–6 months at the time of surgery. Nineteen patients were younger than 6 weeks at the time of surgery. The mean operating time was longer for LP (161 ± 43 min) than that for OP (109 ± 32 min, p < 0.001). However, the mean operating time was not longer in the patient group receiving LP at ≤6 weeks (145 ± 21.6) compared to that in our main cohort receiving LP. There was no significant difference in the length of stay between the groups. Four patients after LP required emergency nephrostomy compared to one patient after OP. The rate of revision pyeloplasty in our main cohort aged 0–6 months at surgery was 8% in the patient group receiving LP and 14% in the patient group receiving OP (not significant). Three revisions after LP were due to persistent UPJO, and one was due to stent migration. Only one patient requiring revision pyeloplasty was less than 6 weeks old.

Conclusion

To our knowledge, this is one of the largest collectives of laparoscopic pyeloplasty performed in infants, and it is the youngest cohort published to date. Based on our experience, LP in neonates and infants under 6 months appears to be as effective as open surgery.
A narrative review on the role of cytokines in the pathogenesis and treatment of familial Mediterranean fever: an emphasis on pediatric cases
Authors: Chaaban Ahlam , Yassine Hasan , Hammoud Razane , Kanaan Ruba , Karam Louna , Ibrahim José-Noel
Published: July 2024

Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disease characterized by an early onset of recurrent fever and serositis episodes. FMF is caused by mutations in the MEFV gene which encodes the pyrin protein, an IL-1β mediated inflammation regulator. Recent findings have identified a plethora of molecules and pathways involved in the regulation of inflammation and innate immunity, hence increasing our understanding of the etiology and inflammatory nature of FMF. Cytokines, in particular, have been found to play a key role in the pathogenesis and treatment of the disease. Indeed, various studies associated cytokines’ genetic variations and expression with susceptibility to and severity of the disease, which was further supported by the positive response of patients, both children and adults, to targeted cytokine blocking therapies. These studies highlighted the potential use of cytokines as biomarkers and target in resistant/intolerant patients and contributed to improving the early detection of FMF in children, thus enhancing their quality of life and providing alternative treatment for severe cases. The aim of this review is to provide the latest updates on the pivotal role of cytokines in FMF and to discuss the efficacy and safety of anti-cytokine biologics by primarily focusing on pediatric FMF cases.
A novel probiotic formula, BLLL, ameliorates chronic stress-induced depression-like behaviors in mice by reducing neuroinflammation and increasing neurotrophic factors
Authors: Ye Minxiu , Ji Feng , Huang Chao , Li Fu , Zhang Changliang , Zhang Yu , Wang Runxin , Ma Kai , Lu Xu , Wang Hui
Published: July 2024

Introduction: Probiotics have been recognized for their various biological activities, including antioxidant and anti-inflammatory properties. This study investigates the therapeutic effect of a novel probiotic formula, BLLL, consisting of Bifidobacterium breve, Lactobacillus plantarum, Lactobacillus paracasei, and Lactobacillus helveticus, on chronic stress-induced depression-like behaviors in mice.

Methods: The BLLL formula or phosphate-buffered saline (PBS) was given orally at a dose of 2, 4, or 8 × 1010 CFU/kg once daily for 10 days in mice treated with chronic unpredictable stress (CUS) treated or vehicle. Depression-like behaviors were assessed using the sucrose preference test (SPT), the forced swimming test (FST), and the tail suspension test (TST). The mRNA and/or protein expression of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), IL-4, IL-10, and chitinase-3-like protein 3 (CHI3L1, also known as Ym-1), as well as the concentration of nitrite, malondialdehyde (MDA), glutathione (GSH), and brain-derived neurotrophic factor (BDNF) in the hippocampus and medial prefrontal cortex were examined.

Results: The BLLL formula treatment at a dose of 8 × 1010 CFU/kg, but not at a dose of 2 or 4 × 1010 CFU/kg, improved CUS-induced depression-like behaviors in mice, as shown by the decrease in immobility time in the TST and FST and the increase in sucrose intake in the SPT. Further analysis revealed that BLLL treatment suppressed the CUS-induced increase in IL-1β, IL-6, and TNF-α mRNA and protein levels, as well as the CUS-induced decrease in IL-4, IL-10, and Ym-1 mRNA and/or protein levels in the hippocampus and medial prefrontal cortex. In addition, treatment with the BLLL formula countered the CUS-induced increase in nitrite and MDA levels and the CUS-induced decrease in GSH content and BDNF concentration in the hippocampus and medial prefrontal cortex.

Conclusion: These results demonstrate that the novel probiotic formula BLLL ameliorates chronic stress-induced depression-like behavior in mice by suppressing neuroinflammation and oxido-nitrosative stress in the brain.
Integrating Mendelian randomization and single-cell RNA sequencing to identify therapeutic targets of baicalin for type 2 diabetes mellitus
Authors: Liang Ying-Chao , Li Ling , Liang Jia-Lin , Liu De-Liang , Chu Shu-Fang , Li Hui-Lin
Published: July 2024

Background

Alternative and complementary therapies play an imperative role in the clinical management of Type 2 diabetes mellitus (T2DM), and exploring and utilizing natural products from a genetic perspective may yield novel insights into the mechanisms and interventions of the disorder.

Methods

To identify the therapeutic target of baicalin for T2DM, we conducted a Mendelian randomization study. Druggable targets of baicalin were obtained by integrating multiple databases, and target-associated cis-expression quantitative trait loci (cis-eQTL) originated from the eQTLGen consortium. Summary statistics for T2DM were derived from two independent genome-wide association studies available through the DIAGRAM Consortium (74,124 cases vs. 824,006 controls) and the FinnGen R9 repository (9,978 cases vs. 12,348 controls). Network construction and enrichment analysis were applied to the therapeutic targets of baicalin. Colocalization analysis was utilized to assess the potential for the therapeutic targets and T2DM to share causative genetic variations. Molecular docking was performed to validate the potency of baicalin. Single-cell RNA sequencing was employed to seek evidence of therapeutic targets’ involvement in islet function.

Results

Eight baicalin-related targets proved to be significant in the discovery and validation cohorts. Genetic evidence indicated the expression of ANPEP, BECN1, HNF1A, and ST6GAL1 increased the risk of T2DM, and the expression of PGF, RXRA, SREBF1, and USP7 decreased the risk of T2DM. In particular, SREBF1 has significant interaction properties with other therapeutic targets and is supported by strong colocalization. Baicalin had favorable combination activity with eight therapeutic targets. The expression patterns of the therapeutic targets were characterized in cellular clusters of pancreatic tissues that exhibited a pseudo-temporal dependence on islet cell formation and development.

Conclusion

This study identified eight potential targets of baicalin for treating T2DM from a genetic perspective, contributing an innovative analytical framework for the development of natural products. We have offered fresh insights into the connections between therapeutic targets and islet cells. Further, fundamental experiments and clinical research are warranted to delve deeper into the molecular mechanisms of T2DM.
Glycerophosphoinositol modulates FGA and NOTCH3 in exercise-induced muscle adaptation and colon cancer progression
Authors: Luo Hongbiao , Luo Wei , Ding Ning , Zhu Huimin , Lai Jiahui , Tang Qingzhu , He Yongheng
Published: July 2024

Objectives

Fibroleukin (FGA) and NOTCH3 are vital in both exercise-induced muscle adaptation and colon adenocarcinoma (COAD) progression. This study aims to elucidate the roles of FGA and NOTCH3 in phenotypic variations of striated muscle induced by exercise and in COAD development. Additionally, it seeks to evaluate the prognostic significance of these proteins.

Methods

Gene Set Variation Analysis (GSVA) and protein-protein interaction (PPI) network analysis were employed to identify differentially expressed genes (DEGs). Molecular docking studies were conducted to assess the binding affinities of 39 compounds to the NOTCH3 protein. In vitro assays, including mobileular viability, gene expression, and apoptosis assays, were performed to evaluate the effects of glycerophosphoinositol on FGA and NOTCH3 expression. Additionally, copy number variation (CNV), methylation status, and survival analyses were conducted across multiple cancers types.

Results

The NOTCH signaling pathway was consistently upregulated in exercise-induced muscle samples. High NOTCH3 expression was associated with poor prognosis in COAD, extracellular matrix organization, immune infiltration, and activation of the PI3K-Akt pathway. Molecular docking identified gamma-Glu-Trp, gamma-Glutamyltyrosine, and 17-Deoxycortisol as strong binders to NOTCH3. Glycerophosphoinositol treatment modulated FGA and NOTCH3 expression, influencing cell proliferation and apoptosis. CNV and methylation analyses revealed specific changes in FGA and NOTCH3 across 20 cancers types. Survival analyses showed strong associations between FGA/NOTCH3 expression and survival metrics, with negative correlations for FGA and positive correlations for NOTCH3.

Conclusion

FGA and NOTCH3 play significant roles in exercise-induced muscle adaptation and colon cancer progression. The expression profiles and interactions of these proteins provide promising prognostic markers and therapeutic targets. These findings offer valuable insights into the post-translational modifications (PTMs) in human cancer, highlighting novel pharmacological and therapeutic opportunities.
Association between sleep duration and cardiovascular risk: the EVasCu cross-sectional study
Authors: Martínez-García Irene , Saz-Lara Alicia , Cavero-Redondo Iván , Otero-Luis Iris , Gómez-Guijarro María Dolores , Moreno-Herraiz Nerea , López-López Samuel , Pascual-Morena Carlos
Published: July 2024

Introduction

Some cardiovascular risk markers have been associated with alterations in sleep duration in different populations; however, there is little evidence in a healthy population.

Aim

The aim of the present study was to analyze the associations between sleep duration and cardiovascular risk biomarkers, including advanced glycation end-products (AGEs) measured by skin autofluorescence (SAF), maximum carotid intima-media thickness (IMTMax), aortic pulse wave velocity (a-PWV), pulse pressure (PP), and low-density lipoprotein cholesterol (LDL-C), in healthy adults (EVasCu study).

Methodology

The EVasCu study included 390 participants. Simple and multiple linear regressions were performed between sleep duration and cardiovascular risk markers. ANOVA analysis and ANCOVA analysis adjusted for various covariates were then performed after categorizing sleep into 6 h, 6–8 h, and >8 h.

Results

296 participants were included in the analyses (43.97 ± 12.60 years, 63.9% female). Simple linear regressions showed an inverse association between sleep duration and SAF, IMTMax, aPWV and PP. However, in the multiple linear regression with all the covariates, the statistical significance was lost. For its part, in the ANOVA analyses, sleep duration was also associated with the same parameters, but when performing the fully adjusted ANCOVA analyses, the statistical significance for SAF was maintained (p = 0.015), obtaining a difference of 0.223 arbitrary units (p = 0.017) when comparing the group <6 h vs. > 8 h. Finally, there was no association for LDL-C.

Conclusion

An inverse association was found between sleep duration and APS, which is considered a marker of cardiovascular risk. Although prospective studies are needed, it is suggested that insufficient sleep may increase cardiovascular risk, which could be a key factor in future public health policies to promote health and prevent CVD.