bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular and functional profiling of cell diversity and identity in the lateral superior olive, an auditory brainstem center with ascending and descending projections
Authors: Maraslioglu-Sperber Ayse , Pizzi Erika , Fisch Jonas O. , Kattler Kathrin , Ritter Tamara , Friauf Eckhard
Published: May 2024

The lateral superior olive (LSO), a prominent integration center in the auditory brainstem, contains a remarkably heterogeneous population of neurons. Ascending neurons, predominantly principal neurons (pLSOs), process interaural level differences for sound localization. Descending neurons (lateral olivocochlear neurons, LOCs) provide feedback into the cochlea and are thought to protect against acoustic overload. The molecular determinants of the neuronal diversity in the LSO are largely unknown. Here, we used patch-seq analysis in mice at postnatal days P10-12 to classify developing LSO neurons according to their functional and molecular profiles. Across the entire sample (n = 86 neurons), genes involved in ATP synthesis were particularly highly expressed, confirming the energy expenditure of auditory neurons. Two clusters were identified, pLSOs and LOCs. They were distinguished by 353 differentially expressed genes (DEGs), most of which were novel for the LSO. Electrophysiological analysis confirmed the transcriptomic clustering. We focused on genes affecting neuronal input–output properties and validated some of them by immunohistochemistry, electrophysiology, and pharmacology. These genes encode proteins such as osteopontin, Kv11.3, and Kvβ3 (pLSO-specific), calcitonin-gene-related peptide (LOC-specific), or Kv7.2 and Kv7.3 (no DEGs). We identified 12 “Super DEGs” and 12 genes showing “Cluster similarity.” Collectively, we provide fundamental and comprehensive insights into the molecular composition of individual ascending and descending neurons in the juvenile auditory brainstem and how this may relate to their specific functions, including developmental aspects.
Global trends and hotspots in pain associated with bipolar disorder in the last 20 years: a bibliometric analysis
Authors: Zhao Hong Qing , Zhou Mi , Jiang Jia Qi , Luo Zhi Qiang , Wang Yu Hong
Published: May 2024

Purpose

The prevalence of comorbid pain and Bipolar Disorder in clinical practice continues to be high, with an increasing number of related publications. However, no study has used bibliometric methods to analyze the research progress and knowledge structure in this field. Our research is dedicated to systematically exploring the global trends and focal points in scientific research on pain comorbidity with bipolar disorder from 2003 to 2023, with the goal of contributing to the field.

Methods

Relevant publications in this field were retrieved from the Web of Science core collection database (WOSSCC). And we used VOSviewer, CiteSpace, and the R package “Bibliometrix” for bibliometric analysis.

Results

A total of 485 publications (including 360 articles and 125 reviews) from 66 countries, 1019 institutions, were included in this study. Univ Toront and Kings Coll London are the leading research institutions in this field. J Affect Disorders contributed the largest number of articles, and is the most co-cited journal. Of the 2,537 scholars who participated in the study, Stubbs B, Vancampfort D, and Abdin E had the largest number of articles. Stubbs B is the most co-cited author. “chronic pain,” “neuropathic pain,” “psychological pain” are the keywords in the research.

Conclusion

This is the first bibliometric analysis of pain-related bipolar disorder. There is growing interest in the area of pain and comorbid bipolar disorder. Focusing on different types of pain in bipolar disorder and emphasizing pain management in bipolar disorder are research hotspots and future trends. The study of pain related bipolar disorder still has significant potential for development, and we look forward to more high-quality research in the future.
Neurologic music therapy for non-fluent aphasia: a systematic review and meta-analysis of randomized controlled trials
Authors: Gu Jiayi , Long Wei , Zeng Siqin , Li Chengjuan , Fang Cuini , Zhang Xiaoying
Published: May 2024

Introduction

The efficacy of neurologic music therapy (NMT) techniques for the treatment of non-fluent aphasia has been widely accepted by the rehabilitation medical community. However, consensus on which dimensions of speech function can be improved by NMT techniques and standardized intervention dosage remains elusive. This study aimed to provide evidence regarding the efficacy of NMT in improving speech function and explore the optimal intervention dose. A systematic review and meta-analysis were conducted to search for randomized clinical trials and open-label trials that evaluated speech functions after NMT.

Methods

We searched all papers and reviews published from database inception to July 2023, including PubMed, Cochrane Library, Web of Science, Embase, and CNKI. Statistical analyses were mainly carried out on RevManV5.4.1 and pooled using a random-effects model. The primary outcome was the standardized mean difference (SMD) in speech functions, determined by calculating the change in speech functions score from baseline to the primary endpoint in the NMT group versus the control arm.

Results

A total of 11 studies with 329 patients were included. NMT had a positive effect on repetition ability (SMD = 0.37, 95%CI [0.12, 0.62], p  < 0.05), but did not lead to significant differences in naming, comprehension, spontaneous speech, or communication. When the intervention time was >20 h, NMT exhibited a significant advantage at improving repetition ability (SMD = 0.43, 95%CI [0.06, 0.79], p  < 0.05).

Discussion

This study provides evidence supporting the NMT enhancement of repetition ability in patients with non-fluent aphasia. Future large-sample studies are required to determine the optimal intervention dose of music therapy for different subtypes of non-fluent aphasia.

Systematic review registration

PROSPERO, identifier CRD42023470313.
State- and frequency-dependence in autonomic rebalance mediated by intradermal auricular electroacupuncture stimulation
Authors: Yang Sen , Wu Yu-Rui , Zhan Zheng , Pan Yan-Hong , Jiang Jin-Feng
Published: May 2024

Background

Vagus nerve stimulation (VNS) improves diseases such as refractory epilepsy and treatment-resistant depression, likely by rebalancing the autonomic nervous system (ANS). Intradermal auricular electro-acupuncture stimulation (iaES) produces similar effects. The aim of this study was to determine the effects of different iaES frequencies on the parasympathetic and sympathetic divisions in different states of ANS imbalance.

Methods

We measured heart rate variability (HRV) and heart rate (HR) of non-modeled (normal) rats with the treatment of various frequencies to determine the optimal iaES frequency. The optimized iaES frequency was then applied to ANS imbalance model rats to elucidate its effects.

Results

30 Hz and 100 Hz iaES clearly affected HRV and HR in normal rats. 30 Hz iaES increased HRV, and decreased HR. 100 Hz iaES decreased HRV, and increased HR. In sympathetic excited state rats, 30 Hz iaES increased HRV. 100 Hz iaES increased HRV, and decreased HR. In parasympathetic excited state rats, 30 Hz and 100 Hz iaES decreased HRV. In sympathetic inhibited state rats, 30 Hz iaES decreased HRV, while 100 Hz iaES decreased HR. In parasympathetic inhibited rats, 30 Hz iaES decreased HR and 100 Hz iaES increased HRV.

Conclusion

30 Hz and 100 Hz iaES contribute to ANS rebalance by increasing vagal and sympathetic activity with different amplifications. The 30 Hz iaES exhibited positive effects in all the imbalanced states. 100 Hz iaES suppressed the sympathetic arm in sympathetic excitation and sympathetic/parasympathetic inhibition and suppressed the vagal arm and promoted the sympathetic arm in parasympathetic excitation and normal states.
Atrophy patterns in hippocampal subregions and their relationship with cognitive function in fibromyalgia patients with mild cognitive impairment
Authors: Long Yingming , Xie Xinyan , Wang Yingwei , Xu Jinping , Gao Ziyi , Fang Xiaokun , Xu Tong , Zhang Nan , Lv Dongling , Wu Ting
Published: May 2024

Objectives

Fibromyalgia (FM) has been associated with decreased hippocampal volume; however, the atrophy patterns of hippocampal subregions have not yet been identified. We therefore aimed to evaluate the volumes of hippocampal subregions in FM patients with mild cognitive impairment (MCI), and to explore the relationship between different subregional alterations and cognitive function.

Methods

The study included 35 FM patients (21 with MCI and 14 without MCI) and 35 healthy subjects. All subjects performed the Montreal Cognitive Assessment (MoCA) to assess cognitive function. FreeSurfer V.7.3.2 was used to calculate hippocampal subregion volumes. We then compared hippocampal subregion volumes between the groups, and analyzed the relationship between hippocampal subregion volume and cognitive function using a partial correlation analysis method.

Results

Compared with the healthy subjects, FM patients with MCI had smaller hippocampal volumes in the left and right CA1 head, Molecular layer head, GC-DG head, and CA4 head, and in the left Presubiculum head. Poorer executive function, naming ability, and attention were associated with left CA1 head and left Molecular layer head atrophy. By contrast, hippocampal subregion volumes in the FM patients without MCI were slightly larger than or similar to those in the healthy subjects, and were not significantly correlated with cognitive function.

Conclusion

Smaller volumes of left CA1 head and left Molecular layer head were associated with poorer executive function, naming ability, and attention in FM patients with MCI. However, these results were not observed in the FM patients without MCI. These findings suggest that the hippocampal subregions of FM patients might present compensatory mechanisms before cognitive decline occurs.
Construction and validation of an endoscopic ultrasonography-based ultrasomics nomogram for differentiating pancreatic neuroendocrine tumors from pancreatic cancer
Authors: Mo Shuangyang , Huang Cheng , Wang Yingwei , Zhao Huaying , Wei Haixiao , Qin Haiyan , Jiang Haixing , Qin Shanyu
Published: May 2024

Objectives

To develop and validate various ultrasomics models based on endoscopic ultrasonography (EUS) for retrospective differentiating pancreatic neuroendocrine tumors (PNET) from pancreatic cancer.

Methods

A total of 231 patients, comprising 127 with pancreatic cancer and 104 with PNET, were retrospectively enrolled. These patients were randomly divided into either a training or test cohort at a ratio of 7:3. Ultrasomics features were extracted from conventional EUS images, focusing on delineating the region of interest (ROI) for pancreatic lesions. Subsequently, dimensionality reduction of the ultrasomics features was performed by applying the Mann-Whitney test and least absolute shrinkage and selection operator (LASSO) algorithm. Eight machine learning algorithms, namely logistic regression (LR), light gradient boosting machine (LightGBM), multilayer perceptron (MLP), random forest (RF), extra trees, k nearest neighbors (KNN), support vector machine (SVM), and extreme gradient boosting (XGBoost), were employed to train prediction models using nonzero coefficient features. The optimal ultrasomics model was determined using a ROC curve and utilized for subsequent analysis. Clinical-ultrasonic features were assessed using both univariate and multivariate logistic regression. An ultrasomics nomogram model, integrating both ultrasomics and clinical-ultrasonic features, was developed.

Results

A total of 107 EUS-based ultrasomics features were extracted, and 6 features with nonzero coefficients were ultimately retained. Among the eight ultrasomics models based on machine learning algorithms, the RF model exhibited superior performance with an AUC= 0.999 (95% CI 0.9977 - 1.0000) in the training cohort and an AUC= 0.649 (95% CI 0.5215 - 0.7760) in the test cohort. A clinical-ultrasonic model was established and evaluated, yielding an AUC of 0.999 (95% CI 0.9961 - 1.0000) in the training cohort and 0.847 (95% CI 0.7543 - 0.9391) in the test cohort. Subsequently, the ultrasomics nomogram demonstrated a significant improvement in prediction accuracy in the test cohort, as evidenced by an AUC of 0.884 (95% CI 0.8047 - 0.9635) and confirmed by the Delong test. The calibration curve and decision curve analysis (DCA) depicted this ultrasomics nomogram demonstrated superior accuracy. They also yielded the highest net benefit for clinical decision-making compared to alternative models.

Conclusions

A novel ultrasomics nomogram was proposed and validated, that integrated clinical-ultrasonic and ultrasomics features obtained through EUS, aiming to accurately and efficiently identify pancreatic cancer and PNET.
Blood cell indices and inflammation-related markers with kidney cancer risk: a large-population prospective analysis in UK Biobank
Authors: He Qingliu , Wei Chengcheng , Cao Li , Zhang Pu , Zhuang Wei , Cai Fangzhen
Published: May 2024

Background

Kidney cancer is a prevalent malignancy with an increasing incidence worldwide. Blood cell indices and inflammation-related markers have shown huge potential as biomarkers for predicting cancer incidences, but that is not clear in kidney cancer. Our study aims to investigate the correlations of blood cell indices and inflammation-related markers with kidney cancer risk.

Methods

We performed a population-based cohort prospective analysis using data from the UK Biobank. A total of 466,994 participants, free of kidney cancer at baseline, were included in the analysis. The hazard ratios (HRs) and 95% confidence intervals (CIs) for kidney cancer risk were calculated using Cox proportional hazards regression models. Restricted cubic spline models were used to investigate nonlinear longitudinal associations. Stratified analyses were used to identify high-risk populations. The results were validated through sensitivity analyses.

Results

During a mean follow-up of 12.4 years, 1,710 of 466,994 participants developed kidney cancer. The Cox regression models showed that 13 blood cell indices and four inflammation-related markers were associated with kidney cancer incidence. The restricted cubic spline models showed non-linear relationships with kidney cancer. Finally, combined with stratified and sensitivity analyses, we found that the mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW), platelet distribution width (PDW), systemic immune-inflammation index (SII), and product of platelet count and neutrophil count (PPN) were related to enhanced kidney cancer risk with stable results.

Conclusion

Our findings identified that three blood cell indices (MCHC, RDW, and PDW) and two inflammation-related markers (SII and PPN) were independent risk factors for the incidence of kidney cancer. These indexes may serve as potential predictors for kidney cancer and aid in the development of targeted screening strategies for at-risk individuals.
Continuous response despite reduced dose of trametinib as single agent in an adolescent with a relapsed disseminated pediatric low-grade glioma KIAA1549-BRAF fusion positive: a case report and review of the literature
Authors: Castellano-Damaso Serafin , Vazquez-Gomez Felisa , Moreno-Carrasco Jose Luis , Arce Begoña , Borrego Pedro , Lassaletta Alvaro
Published: May 2024

Dissemination in pediatric low-grade glioma may occur in about 4%–10% of patients according to retrospective cohort studies. Due to its low incidence, there is no consensus on treatment for these patients. According to the constitutional activation of the MAPK/ERK pathway in these tumors, MEK inhibitors such as trametinib have been used successfully in the relapsed setting. Skin toxicity is frequent in patients receiving trametinib, normally mild to moderate, but sometimes severe, needing to discontinue the drug, limiting the efficacy in the tumor. There is not much information in the literature regarding whether reducing the dose of trametinib is able to maintain efficacy while, at the same time, decreasing toxicity. Here, we present an adolescent, with severe skin toxicity, whose trametinib dose was reduced by 50% and efficacy on the tumor continued while skin toxicity significantly decreased.
Current landscape of primary small bowel leiomyosarcoma: cases report and a decade of insights
Authors: Zhou Junjie , Xu Houyun , Hu Jibo , Hong Qiang , Yu Xiping , Liu Wei , Zhao Jiaxin , Hu Hongjie
Published: May 2024

The incidence of leiomyosarcoma (LMS) is about 4–5/100,000 individuals per year. LMSs occurring in the small bowel are even rarer, and their preoperative diagnosis is very difficult. We described two patients with pathologically confirmed small bowel LMS and analyzed their clinical and medical imaging features. Similar cases reported in English in Pubmed database over the past decade were reviewed and summarized. These tumors were categorized by the growth direction and relationship with the intestinal lumen into three types: intraluminal (n = 10), intermural (n = 3), and extraluminal (n = 7). Notably, among the three types of LMS, the intramural leiomyosarcoma stands out as a noteworthy subtype. Emerging evidence suggests that smaller tumor size (< 5 cm) and the intraluminal type may serve as favorable prognostic indicators, while the extraluminal type is associated with relatively poor prognosis. Furthermore, the integration of imaging features with CA125 and LDH biomarkers holds promise for potential diagnostic value in LMS.
Causal relationship between iron deficiency anemia and asthma: a Mendelian randomization study
Authors: Li Mengchun , Chen Zhengdong , Yang Xin , Li Wanwei
Published: May 2024

Background

Observational studies have suggested an association between iron deficiency anemia (IDA) and asthma, which may affect the occurrence of asthma. However, whether IDA is a new management goal for asthma remains to be determined.

Objective

We conducted a two-sample Mendelian randomization(MR)analysis to assess the association between IDA and asthma.

Methods

We performed a two-sample MR study to assess a causal relationship between IDA (ncase = 12,434, ncontrol = 59,827) and asthma (ncase = 20,629, ncontrol = 135,449). Inverse variance weighted (IVW) was used as the primary method for the analyses. Furthermore, we used weighted medians and MR-Egger to enhance robustness. Data linking genetic variation to IDA and asthma were combined to assess the impact of IDA on asthma risk.

Results

There are five single nucleotide polymorphisms (SNPs) were used as genetic tool variables for exposure factors. Genetically determined IDA was significantly associated with an increased risk of asthma (OR = 1.37, 95% CI: 1.09–1.72, p = 0.007). There was little heterogeneity in the MR studies and no evidence of level pleiotropy was found.

Conclusions

In our MR study, our findings emphasize that IDA may be associated with a high risk of asthma, indicating a potential role for IDA in the development of asthma. Future research needs to elucidate its potential mechanisms to pave the way for the prevention and treatment of asthma.
Inducing ferroptosis by traditional medicines: a novel approach to reverse chemoresistance in lung cancer
Authors: Wang Yumin , Hu Jing , Fleishman Joshua S. , Li Yulin , Ren Zhao , Wang Jinhua , Feng Yukuan , Chen Jichao , Wang Hongquan
Published: May 2024

Lung cancer is the leading cause of global cancer-related deaths. Platinum-based chemotherapy is the first-line treatment for the most common type of lung cancer, i.e., non-small-cell lung cancer (NSCLC), but its therapeutic efficiency is limited by chemotherapeutic resistance. Therefore, it is vital to develop effective therapeutic modalities that bypass the common molecular mechanisms associated with chemotherapeutic resistance. Ferroptosis is a form of non-apoptotic regulated cell death characterized by iron-dependent lipid peroxidation (LPO). Ferroptosis is crucial for the proper therapeutic efficacy of lung cancer-associated chemotherapies. If targeted as a novel therapeutic mechanism, ferroptosis modulators present new opportunities for increasing the therapeutic efficacy of lung cancer chemotherapy. Emerging studies have revealed that the pharmacological induction of ferroptosis using natural compounds boosts the efficacy of chemotherapy in lung cancer or drug-resistant cancer. In this review, we first discuss chemotherapeutic resistance (or chemoresistance) in lung cancer and introduce the core mechanisms behind ferroptosis. Then, we comprehensively summarize the small-molecule compounds sourced from traditional medicines that may boost the anti-tumor activity of current chemotherapeutic agents and overcome chemotherapeutic resistance in NSCLC. Cumulatively, we suggest that traditional medicines with ferroptosis-related anticancer activity could serve as a starting point to overcome chemotherapeutic resistance in NSCLC by inducing ferroptosis, highlighting new potential therapeutic regimens used to overcome chemoresistance in NSCLC.
Pharmacokinetic assessment of tacrolimus in combination with deoxyschizandrin in rats
Authors: Sun Jianguo , Wang Zhipeng , Liu Na , Liu Zhijun , Cui Lili , Tao Xia , Chen Wansheng , Gao Shouhong , Wu Zhijun
Published: May 2024

Background

Tacrolimus (Tac) is commonly used for postoperative immunosuppressive therapy in transplant patients. However, problems, for example, low bioavailability and unstable plasma concentration, persist for a long time, Studies have reported that the deoxyschizandrin could effectively improve these problems, but the pharmacokinetic parameters (PKs) of Tac combined with deoxyschizandrin are still unknown.

Method

In this study, an UHPLC-MS/MS method has been established for simultaneous quantitation of Tac and deoxyschizandrin. The PKs of Tac influenced by different doses of deoxyschizandrin after single and multiple administrations were analyzed, and the different impact of deoxyschizandrin and Wuzhi capsule on PKs of Tac were compared.

Result

The modified UHPLC-MS/MS method could rapid quantification of Tac and deoxyschizandrin within 2 min using bifendatatum as the internal standard (IS). All items were successfully validated. The Cmax of deoxyschizandrin increased from 148.27 ± 23.20 to 229.13 ± 54.77 ng/mL in rats after multiple administrations for 12 days. After co-administration of 150 mg/mL deoxyschizandrin, Tac had an earlier Tmax and greater Cmax and AUC0–t, and the Cmax and AUC0–t of Tac increased from 14.26 ± 4.73 to 54.48 ± 14.37 ng/mL and from 95.10 ± 32.61 to 315.23 ± 92.22 h/ng/mL, respectively; this relationship was positively proportional to the dosage of deoxyschizandrin. In addition, compared with Wuzhi capsule, the same dose of deoxyschizandrin has a better effective on Tac along with more stable overall PKs.

Conclusion

An UHPLC-MS/MS method was established and validated for simultaneous detection of deoxyschizandrin and Tac. Deoxyschizandrin could improve the in vivo exposure level and stability of Tac, besides, this effect is better than Wuzhi capsule in same dose.
Modified oxylipins as inhibitors of biofilm formation in Staphylococcus epidermidis
Authors: Peran Jacquelyn E. , Salvador-Reyes Lilibeth A.
Published: May 2024

New approaches to combating microbial drug resistance are being sought, with the discovery of biofilm inhibitors considered as alternative arsenal for treating infections. Natural products have been at the forefront of antimicrobial discovery and serve as inspiration for the design of new antibiotics. We probed the potency, selectivity, and mechanism of anti-biofilm activity of modified oxylipins inspired by the marine natural product turneroic acid. Structure-activity relationship (SAR) evaluation revealed the importance of the trans-epoxide moiety, regardless of the position, for inhibiting biofilm formation. trans-12,13-epoxyoctadecanoic acid (1) and trans-9,10 epoxyoctadecanoic acid (4) selectively target the early stage of biofilm formation, with no effect on planktonic cells. These compounds interrupt the formation of a protective polysaccharide barrier by significantly upregulating the ica operon’s transcriptional repressor. This was corroborated by docking experiment with SarA and scanning electron micrographs showing reduced biofilm aggregates and the absence of thread-like structures of extrapolymeric substances. In silico evaluation revealed that 1 and 4 can interfere with the AgrA-mediated communication language in Staphylococci, typical to the diffusible signal factor (DSF) capacity of lipophilic chains.
Ferroptosis inhibitors: past, present and future
Authors: Zhang Lei , Luo Yi Lin , Xiang Yang , Bai Xin Yue , Qiang Rong Rong , Zhang Xin , Yang Yan Ling , Liu Xiao Long
Published: May 2024

Ferroptosis is a non-apoptotic mode of programmed cell death characterized by iron dependence and lipid peroxidation. Since the ferroptosis was proposed, researchers have revealed the mechanisms of its formation and continue to explore effective inhibitors of ferroptosis in disease. Recent studies have shown a correlation between ferroptosis and the pathological mechanisms of neurodegenerative diseases, as well as diseases involving tissue or organ damage. Acting on ferroptosis-related targets may provide new strategies for the treatment of ferroptosis-mediated diseases. This article specifically describes the metabolic pathways of ferroptosis and summarizes the reported mechanisms of action of natural and synthetic small molecule inhibitors of ferroptosis and their efficacy in disease. The paper also describes ferroptosis treatments such as gene therapy, cell therapy, and nanotechnology, and summarises the challenges encountered in the clinical translation of ferroptosis inhibitors. Finally, the relationship between ferroptosis and other modes of cell death is discussed, hopefully paving the way for future drug design and discovery.
Ephedra sinica polysaccharide regulate the anti-inflammatory immunity of intestinal microecology and bacterial metabolites in rheumatoid arthritis
Authors: Ma Yanmiao , Wei Xiuhong , Peng Jiehao , Wei Fuxia , Wen Ya , Liu Mingran , Song Bo , Wang Yonghui , Zhang Yumin , Peng Tao
Published: May 2024

Introduction

Ephedra sinica polysaccharide (ESP) exerts substantial therapeutic effects on rheumatoid arthritis (RA). However, the mechanism through which ESP intervenes in RA remains unclear. A close correlation has been observed between enzymes and derivatives in the gut microbiota and the inflammatory immune response in RA.

Methods

A type II collagen-induced arthritis (CIA) mice model was treated with Ephedra sinica polysaccharide. The therapeutic effect of ESP on collagen-induced arthritis mice was evaluated. The anti-inflammatory and cartilage-protective effects of ESP were also evaluated. Additionally, metagenomic sequencing was performed to identify changes in carbohydrate-active enzymes and resistance genes in the gut microbiota of the ESP-treated CIA mice. Liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry were performed to observe the levels of serum metabolites and short-chain fatty acids in the gut. Spearman’s correlational analysis revealed a correlation among the gut microbiota, antibiotic-resistance genes, and microbiota-derived metabolites.

Results

ESP treatment significantly reduced inflammation levels and cartilage damage in the CIA mice. It also decreased the levels of pro-inflammatory cytokines interleukin (IL)-6, and IL-1-β and protected the intestinal mucosal epithelial barrier, inhibiting inflammatory cell infiltration and mucosal damage. Here, ESP reduced the TLR4, MyD88, and TRAF6 levels in the synovium, inhibited the p65 expression and pp65 phosphorylation in the NF-κB signaling pathway, and blocked histone deacetylase (HDAC1 and HDAC2) signals. ESP influenced the gut microbiota structure, microbial carbohydrate-active enzymes, and microbial resistance related to resistance genes. ESP increased the serum levels of L-tyrosine, sn-glycero-3-phosphocholine, octadecanoic acid, N-oleoyl taurine, and decreased N-palmitoyl taurine in the CIA mice.

Conclusion

ESP exhibited an inhibitory effect on RA. Its action mechanism may be related to the ability of ESP to effectively reduce pro-inflammatory cytokines levels, protect the intestinal barrier, and regulate the interaction between mucosal immune systems and abnormal local microbiota. Accordingly, immune homeostasis was maintained and the inhibition of fibroblast-like synoviocyte (FLS) proliferation through the HDAC/TLR4/NF-κB pathway was mediated, thereby contributing to its anti-inflammatory and immune-modulating effects.
Urban and social resilience—the role of cities and civil society organizations in the Search and Rescue system in the Mediterranean
Authors: Trombetta Isabella
Published: May 2024

Search and Rescue (SAR) in the Central Mediterranean has been at the center of the European debate on migration management of the past decade. In response to the challenges posed by maritime rescue operations, European governments have increasingly centralized their efforts through Frontex operations, departing from the previous collaborative framework with SAR NGOs that was established in the aftermath of the Lampedusa shipwreck. The political discourse has predominantly focused on the designation and definition of a Port of Safety, sidelining the imperative need for an effective SAR infrastructure, leading to life-threatening impasses at sea, and also leading to the complete disregard for the agency and will of cities. While the cooperation between governments, cities, and civil society organizations has been at the center of successful decentralized migration management efforts on land, a contrasting trend of centralization and diminished cooperation has emerged at sea in the Central Mediterranean. The article argues that the European Union’s shift from SAR-oriented efforts to border management has resulted in heightened inefficiencies within the Mediterranean SAR infrastructure. This inefficiency is attributed to the diminished collaboration with NGOs and local entities. Utilizing the category of resilience as a theoretical framework of migration management, the article will address the role of cities and NGOs in the creation of a coordinated SAR system in the Mediterranean.
Computational analysis of value learning and value-driven detection of neutral faces by young and older adults
Authors: Namba Shushi , Saito Akie , Sato Wataru
Published: May 2024

The rapid detection of neutral faces with emotional value plays an important role in social relationships for both young and older adults. Recent psychological studies have indicated that young adults show efficient value learning for neutral faces and the detection of “value-associated faces,” while older adults show slightly different patterns of value learning and value-based detection of neutral faces. However, the mechanisms underlying these processes remain unknown. To investigate this, we applied hierarchical reinforcement learning and diffusion models to a value learning task and value-driven detection task that involved neutral faces; the tasks were completed by young and older adults. The results for the learning task suggested that the sensitivity of learning feedback might decrease with age. In the detection task, the younger adults accumulated information more efficiently than the older adults, and the perceptual time leading to motion onset was shorter in the younger adults. In younger adults only, the reward sensitivity during associative learning might enhance the accumulation of information during a visual search for neutral faces in a rewarded task. These results provide insight into the processing linked to efficient detection of faces associated with emotional values, and the age-related changes therein.
A study on the influence of dominant sound sources on users’ emotional perception in a pediatric dentistry clinic
Authors: Liu Yang , Chen Xi
Published: May 2024

Introduction

Soundscape in dental clinics has varying degrees of impact on the emotions of healthcare workers and young patients. Emotions such as restlessness, anxiety, anger, and nervousness are commonly found among dental healthcare workers. Pediatric dental clinics are an important part of dental clinics, but there is a lack of research on the soundscape within pediatric dental clinics.

Methods

This study focuses on a typical pediatric dental clinic, using a combination of field questionnaires and objective measurements. It aims to determine the impact of dominant sound sources on the emotional perception (nervousness, restlessness, anger, fear, pain) and hostile emotional responses of users in the pediatric dental clinic.

Results

In the soundscape of pediatric dental clinics for young pediatric patients, users experience negative emotional perceptions (nervousness, restlessness, anxiety, anger, fear, and pain) and emotional responses of hostility. The dominant sound sources can be divided into two categories: dental (dental drill, air-water syringe, and saliva ejector) and nondental (children crying). Under the influence of dental dominant sound sources, there was a significant negative correlation between the emotional perceptions of healthcare workers and their negative emotional perceptions (p  <  0.05). Conversely, for young pediatric patients aged 0–11  years, a significant positive correlation was observed between their emotional perceptions and negative emotional perceptions. The mean perceived degrees of nervousness and fear in young pediatric patients were 1.82 and 1.71 times stronger, respectively, than those observed in healthcare workers. Under the influence of non-dental dominant sound sources, the average degree of emotional perception among healthcare workers was 0.71 higher than that of young pediatric patients, and anxiety perception was significantly enhanced (p  <  0.05). The mean degree of nervousness perception was 1 point higher in healthcare workers compared to young pediatric patients, restlessness perception was 1.1 stronger, and there was a presence of mild pain perception. In terms of demographic/social factors, age, occupation, and years of work significantly affected the perceptions of fear and restlessness among healthcare workers, while age had a significant impact on the emotional reaction of hostility in young pediatric patients.

Discussion

The results of this study indicate that the soundscape is an important factor in creating a comfortable treatment environment in pediatric dental clinics. Healthcare workers and young pediatric patients are significantly affected by the dominant sound sources in the clinic, and these effects are closely related to demographic and social factors such as age, profession, and years of experience. This finding can provide more targeted methods and strategies for the design and creation of soundscapes in dental clinics.
Media coverage of COVID-19 vaccination-associated cerebral venous sinus thrombosis was followed by a surge in emergency presentations due to headache – observations from a university hospital in Germany
Authors: Asan Livia , Kleine-Borgmann Julian , Bozkurt Bessime , Frank Benedikt , Köhrmann Martin , Kleinschnitz Christoph , Bingel Ulrike
Published: May 2024

Nocebo effects describe all negative outcomes for well-being brought about by negative health-related expectations. Media coverage of drug side effects can fuel nocebo effects and lead to increased symptom reports. This retrospective observational analysis of emergency reports at the neurological emergency room at University Hospital Essen, Germany, examines whether media communication about a cumulation of very rare cases of cerebral venous sinus thrombosis (CVST) after COVID-19 vaccination with the AstraZeneca compound (ChAdOx-1 nCoV-19) was followed by an increase in weekly presentation rates of patients with the main complaint of headache, a symptom commonly occurring as a vaccination reaction but also communicated as a warning symptom for CVST. The rate of headache presentations increased by 171.7% during the five weeks after the first announcement of CVSTs in Germany on 11 March 2021, compared to the five weeks immediately prior. Furthermore, more young women sought consultation for headache, reflecting the communicated at-risk profile for CVST. The increased rate of headache presenters contributed to a 32.1% rise in total neurological emergency cases, causing an increased strain on the emergency facility after the side effect risk was publicized. We discuss a causal role of negative side effect expectations after vaccination with AstraZeneca as a driver for this increase. While transparent communication about benefits and potential side effects is crucial for vaccination acceptance, increased vigilance toward nocebo effects in health-related media communication is needed due to its potential harm to the individual and society, especially when emergency medical resources are stretched thin.
Self-injury functions mediate the association between anxiety and self-injury frequency among depressed Chinese adolescents: sex differences
Authors: Zhao Yunhan , Zhao Xudong , Zhou Yongjie , Liu Liang
Published: May 2024

Objective

Non-suicidal self-injury (NSSI) has become a common clinical problem that severely threatens the mental and physical health of Chinese adolescents. This study explores the mediation effects of NSSI functions on the relationship between anxiety and NSSI frequency among depressed Chinese adolescents as well as the sex differences in the mediating effects.

Methods

In this study, a cross-sectional survey method was used to obtain data of 1773 adolescent patients with major depressive disorders from over 20 specialized psychiatric hospitals across multiple provinces in China. A self-designed questionnaire for demographic information, the Chinese version of Functional Assessment of Self- Mutilation (C-FASM), and the 7-item Generalized Anxiety Disorder Scale (GAD-7) were employed to investigate demographic data, NSSI frequency, NSSI functions, and anxiety and to analyze the mediating effects of NSSI functions on the association between anxiety and NSSI frequency among adolescents of different sexes.

Results

A total of 316 male patients and 1457 female patients were investigated. Female patients had a higher NSSI frequency (Z=3.195, P=0.001) and higher anxiety scores than did male patients (Z=2.714, P=0.007). Anxiety had a stronger positive predictive effect on the NSSI frequency in females (OR = 1.090) than in males (OR = 1.064). For male patients, the emotion regulation function in NSSI motivation played a full mediating role in the association between anxiety and NSSI frequency. For female patients, the emotion regulation and social avoidance functions in NSSI functions played a partial mediating role between anxiety and NSSI frequency.

Conclusions

There are sex differences in the mediating role of NSSI functions of depressed adolescents in the association between anxiety and NSSI frequency. When experiencing anxiety, both males and females may engage in NSSI behaviors as a means to regulate their emotions. For females, anxiety can directly predict NSSI frequency, and they may attempt NSSI to achieve the purpose of rejecting others. In the face of anxiety among depressed adolescents of different sexes, developing different emotional regulation methods and behavioral regulation strategies may be critical in preventing their NSSI behaviors.
Mendelian randomization shows causal effects of birth weight and childhood body mass index on the risk of frailty
Authors: Cui Junhao , Fu Shuqin , Zhu Lin , Li Peng , Song Chunlan
Published: May 2024

Background

The association between birth weight and childhood body mass index (BMI) and frailty has been extensively studied, but it is currently unclear whether this relationship is causal.

Methods

We utilized a two-sample Mendelian randomization (MR) methodology to investigate the causal effects of birth weight and childhood BMI on the risk of frailty. Instrumental variables (p < 5E-08) strongly associated with own birth weight (N = 298,142 infants), offspring birth weight (N = 210,267 mothers), and childhood BMI (N = 39,620) were identified from large-scale genomic data from genome-wide association studies (GWAS). The frailty status was assessed using the frailty index, which was derived from comprehensive geriatric assessments of older adults within the UK Biobank and the TwinGene database (N = 175,226).

Results

Genetically predicted one standard deviation (SD) increase in own birth weight, but not offspring birth weight (maternal-specific), was linked to a decreased frailty index (β per SD increase = −0.068, 95%CI = −0.106 to −0.030, p = 3.92E-04). Conversely, genetically predicted one SD increase in childhood BMI was associated with an elevated frailty index (β per SD increase = 0.080, 95%CI = 0.046 to 0.114, p = 3.43E-06) with good statistical power (99.8%). The findings remained consistent across sensitivity analyses and showed no horizontal pleiotropy (p > 0.05).

Conclusion

This MR study provides evidence supporting a causal relationship between lower birth weight, higher childhood BMI, and an increased risk of frailty.
“Connect Local”: protocol for the evaluation of a codesigned whole of community approach to promote social connection in older adults
Authors: Ogrin R. , Robinson E. , Rendell K. , Alrababah S. , Fineberg D. , Fiddes K. , Yerolemou A. , Lim M. H. , Engel L. , Lowthian J. A.
Published: May 2024

Background

There is wide acknowledgement in the literature that social connection is protective against loneliness and depression. More robust research, however, is needed to evaluate interventions that promote social connection. This protocol paper outlines the evaluation of a community-wide social connection program, Connect Local, in metropolitan Melbourne, Australia to support people 65 years and older to increase access to local community services/activities; and to ascertain impact on social connection, loneliness, depressive symptoms, physical and mental wellbeing, and use of health services.

Methods

A Type 1 Hybrid design, including program effectiveness, cost-effectiveness, and implementation evaluation of the Connect Local program, will be undertaken. Eighty-eight participants aged ≥65 years with one or more chronic health condition, who are also either experiencing or at risk of loneliness, social isolation and depressive symptoms will be invited to participate in the evaluation. Outcomes, measured at baseline, 3, 6 and 12 months, include loneliness, social isolation, depressive symptoms, social anxiety, goal attainment, wellbeing, quality of life and health care utilisation. A gender and age matched comparator group of 88 individuals will be recruited from outside the intervention local government area. Impact of the intervention on community service providers in the target region will be evaluated using mixed methods, where triangulation will be used to combine the qualitative and quantitative data using a deductive-simultaneous design. Changes in wellbeing and quality of life of community volunteers will also be measured. All groups will be interviewed to ascertain their experience and perceptions of the program. The economic evaluation will use a Social Return on Investment (SROI) approach, to include outcomes at the individual, community, and system levels. Implementation outcomes will consider Reach, Adoption, Feasibility, Acceptability, Appropriateness, Fidelity, and Sustainability of the intervention.

Discussion

This study will provide a better understanding of the impacts of a community-wide social connection approach in older adults, the community and broader system.

Clinical trial registration

https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385192; Identifier ACTRN12623000968673.
The influence of actors on the content and execution of a bereavement programme: a Bourdieu-inspired ethnographical field study in Sweden
Authors: Karidar Hakima , Lundqvist Pia , Glasdam Stinne
Published: May 2024

Introduction

The death of a parent can have profound negative impacts on children, and a lack of adequate support can exacerbate negative life experiences.

Aim

To explore the influences of various actors on the content and execution of a bereavement programme within a Swedish context, considering relational and contextual perspectives.

Methods

An ethnographic field study involving six children, their parents, and eight volunteers. A theory-inspired thematic analysis was conducted, methodically inspired by Braun and Clarke, theoretically inspired by Bourdieu’s concepts of position, power, and capital.

Results

Confidentiality obligation was an essential element in the programme, however, the premisses varied depending on actors’ positions. Volunteers and researchers had different outlets to express their experiences in the program. The programme offered the children an exclusive space for talking about and sharing experiences and feelings. Simultaneously, the programme restricted the children by not allowing them to share their experiences and feelings outside the physical space. The physical settings shaped the different conditions for interactions among the actors. The sessions adopted loss-oriented approaches, where communication between volunteers and children was guided by the volunteers. However, children created strategies for additional, voiceless communication with their peers or themselves. During breaks and mingles, shared interests or spaces connected children (and adults) more than their common experience of parental bereavement.

Conclusion

The participants in the programme were significantly influenced by the structural framework of the programme, and their positions within the programme provided them with different conditions of possibility for (inter)acting. Children’s daily activities and interests were both ways to cope with parental bereavement and connect them to other people.
Summer undergraduate biomedical research program for underrepresented minority students in a rural, low-income state
Authors: Anders Michael E. , Prince Latrina Y. , Williams Tremaine B. , McGehee Robert E. , Thomas Billy R. , Allen Antino R.
Published: May 2024

Introduction

Diversity can enhance the agenda and quality of biomedical research, but a dearth of underrepresented minorities and women serve as biomedical researchers. The study purpose was to examine the impact of the a summer undergraduate research program on self-efficacy in research, scientific communication, and leadership as well as scientific identity, valuing objectives of the scientific community, and intent to pursue a biomedical research career.

Methods

Underrepresented minority and female undergraduate students participated in a mentored research experience in a rural, low-income state.

Results

Students' self-efficacy in research, scientific communication, and leadership as well as scientific identity, valuing objectives of the scientific community, and intent to pursue a biomedical research career increased post-program compared to pre-program.

Conclusion

This study supports implementation of a biomedical summer undergraduate research program for URM and women in a poor, rural, settings.