bluuebunny/crossref_metadata_2025 huggingface dataset:
Promoting integrated STEM education among students via fabrication of interactive exhibit
Authors: Tan Yong Leng Kelvin , Subramaniam R.
Published: November 2024

Few studies in the education literature have focused on integrated STEM in a comprehensive manner and, even among these, there does not seem to be a significant emphasis on all the four disciplines. In addition, there are hardly any studies that focus on transitioning across prototype variants to demonstrate students’ understanding of what they must grapple with, including STEM concepts while coming up with a product. This qualitative study explored how a group of high school students harnessed the constituent disciplines of STEM to fabricate an interactive exhibit on laminar flow in an iterative manner. It was found that in the process of prototyping a working model of the exhibit, the students were able to demonstrate a working understanding of 37 relevant concepts in the four STEM disciplines, with science (14) and engineering (10) predominating, followed by technology (8) and mathematics (5). The students were able to incorporate four levels of interactivity in the exhibit, and this allowed visitors to explore the factors affecting laminar flow in the exhibit during a public exhibition in the school. Examination of the STEM dispositions of the students indicated a positive influence as a result of the activity. To the best of our knowledge, this study has incorporated the highest number of STEM concepts. We argue for the need for more studies that integrate all the four constituent disciplines of STEM in promoting integrated STEM education.
The phenomenon and suppression strategy of overvoltage caused by PV power reverse flow
Authors: Xie Yumeng , Li Qiying , Yang Lei , Yang Kun , Wang Zhen , Liu Jie , Fan Hongjin
Published: November 2024

In the current distribution network’s energy structure, photovoltaic (PV) occupies a high proportion. However, the access of a high proportion of PV will lead to the phenomenon of reverse power flow in the distribution network, and then the problem of line overvoltage. When the reverse power flow increases, the problem of line overvoltage also worsens, which endangers the normal operation of power system. To solve this problem, this paper starts with the voltage rise theory of distribution network lines. Firstly, through strict mathematical derivation, it compares the influence of main network line parameters and distribution network line parameters on the voltage rise, and summarizes a simple calculation equation for the voltage rise of the distribution network with high proportion PV. Then, according to the mechanism of voltage rise and the principle of inverter control, considering the economy and practicability of the overvoltage suppression strategy, a reverse power flow overvoltage suppression strategy of a system with high proportion PV is proposed. Finally, a PV system model simulating a small village is used to verify the effectiveness of the proposed overvoltage suppression strategy.
Healthy lifestyle choices: new insights into vitiligo management
Authors: Liang Xin , Guo Fei , Fan Qian , Cai Xiaoce , Wang Jiao , Chen Jiale , Liu Fang , Du Yuhua , Chen Yan , Li Xin
Published: November 2024

Background

The treatment of vitiligo is complex, and providing guidance based on lifestyle habits is a good option that has not been summarized or analyzed.

Objective

To elucidate the relationship between vitiligo and lifestyle factors.

Methods

Four databases (PubMed, Embase, Cochrane, and China National Knowledge Internet) were searched for articles published between 1980 and December 2022. Keywords such as smoking, drinking, exercise, diet, and sleep were used.

Results

Based on the search strategy, 875 relevant studies were retrieved, and 73 were included in this study, of which 41 studies with 8,542 patients with vitiligo were included in the meta-analysis. Vitamin C [mean difference (MD), −0.342; 95% confidence interval (CI), −1.090–0.407; p >0.05), folic acid (MD, −1.463; 95% CI, −7.133–4.208; p >0.05), and selenium (MD, 0.350; 95% CI, −0.687–1.387; p >0.05) levels did not differ between the groups. Vitamin E (MD, −1.408; 95% CI, −2.611–−0.206; p <0.05), vitamin B12 (MD, −0.951; 95% CI, −1.672–−0.275; p <0.05), copper (MD, −0.719; 95% CI, −1.185–−0.252, p <0.005), and zinc (MD, −0.642; 95% CI, −0.731–−0.554; p <0.001) levels were lower in the vitiligo group than in the control group. The serum iron level of the vitiligo group was significantly higher than that of the control group (MD, 1.181; 95% CI, 0.390–1.972; p <0.005). Finally, more participants in the vitiligo group smoked and drank alcohol than those in the control group.

Limitations

Most studies are from Eastern countries; thus, extrapolating these results to Western populations is questionable. The significant heterogeneity may be attributed to the different stages, types, duration, center settings, population registries, etc., which seriously impair the validity of the results.

Conclusions

Patients with vitiligo should reduce smoking and alcohol consumption and take appropriate vitamin E, B12, copper, and zinc supplements. However, vitamin C, vitamin D, selenium, iron, and folic acid supplements are unnecessary. Moreover, they should consider sun protection and avoid permanent hair dye use. Patients with vitiligo may experience sleep disturbances and sexual dysfunction, and these patients should seek help from a specialist if necessary.

Systematic review registration

https://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD42023480757.
Upregulation of CRISP3 and its clinical values in adult sepsis: a comprehensive analysis based on microarrays and a two-retrospective-cohort study
Authors: Zhang An-qiang , Wen Da-lin , Ma Xin-xin , Zhang Fei , Chen Guo-sheng , Maimaiti Kelimu , Xu Gang , Jiang Jian-xin , Lu Hong-xiang
Published: November 2024

Background

Current lines of evidence indicate that cysteine-rich secretory protein 3 (CRISP3) is an immunoregulatory factor. Nevertheless, no study has explored the relationships between the values of CRISP3 and sepsis.

Methods

We conducted a comprehensive literature search and meta-analysis from the Gene Expression Omnibus (GEO) and ArrayExpress to determine the expression of CRISP3 in sepsis patients. Then, we explored whether plasma CRISP3 could serve as a potential biomarker to predict the risk of sepsis via two retrospective trauma cohorts. We evaluated the prediction power using the area under the curve (AUC).

Results

A total of 23 datasets were recruited for the comprehensive meta-analysis, and the combined standardized mean difference (SMD) of CRISP3 was 0.90 (0.50–1.30) (p < 0.001), suggesting that CRISP3 was overexpressed in sepsis patients. Meanwhile, sepsis patients had higher CRISP3 concentrations than non-sepsis patients in 54 trauma patients (p < 0.001). Plasma CRISP3 on admission was significantly associated with the incidence of sepsis [OR = 1.004 (1.002–1.006), p < 0.001]. As a predictive biomarker, CRISP3 obtained a better AUC [0.811 (0.681–0.905)] than C-reactive protein (CRP) [0.605 (0.463–0.735)], procalcitonin (PCT) [0.554 (0.412–0.689)], and Sequential Organ Failure Assessment (SOFA) [0.754 (0.618–0.861)]. Additionally, the clinical relationships between plasma CRISP3 and sepsis were verified in another trauma cohort with 166 patients [OR = 1.002 (1.001–1.003), p < 0.001]. The AUC of CRISP3 was 0.772 (0.701–0.834), which was better than that of CRP [0.521 (0.442–0.599)] and PCT [0.531 (0.452–0.609)], but not SOFA [0.791 (0.717–0.853)].

Conclusion

Our study indicated and validated that CRISP3 was highly expressed in sepsis. More importantly, CRISP3 may serve as a latent biomarker to predict the risk of sepsis.
Porcine non-conventional B-1-like cells are a potent source of Streptococcus suis-binding IgM
Authors: Seidel Anne-Marie , Kauffold Johannes , Protschka Martina , Baums Christoph G. , Alber Gottfried , Eschke Maria
Published: November 2024

Introduction

Streptococcus suis serotype (cps) 2 is an important bacterial pathogen in piglet nurseries and an emerging zoonotic agent without effective vaccines available. Immunoglobulin (Ig)M plays an essential role in host defense against S. suis. In mice, non-conventional B-1 cells are a major source of protective IgM against encapsulated bacterial pathogens, such as S. pneumoniae. Two IgM+CD21− B-1-like cell subpopulations, distinguishable by CD11R1 expression, were described in pigs, but their properties and functions are poorly understood. This study aimed at a first characterization of the porcine early IgM B cell response against S. suis cps 2.

Methods

We analyzed the same healthy pigs, naturally colonized by different S. suis serotypes, including cps 2, at four and eight weeks of age serologically and determined the frequency of different peripheral B cell subpopulations by flow cytometry. Furthermore, we isolated conventional IgM+CD21+ B-2 cells as well as non-conventional B-1-like cell subpopulations from peripheral blood of eight-weeks-old pigs to evaluate their potential of IgM secretion in response to innate and adaptive stimuli in vitro.

Results

Between the fourth and eighth week of life, a characteristic increase of S. suis cps 2-binding serum IgM antibodies, restricting bacterial growth, was observed. Moreover, we show for the first time that the significant increase of anti-S. suis serum IgM is associated with a relative increase of peripheral non-conventional IgM+CD21− B-1-like cells in vivo, particularly of the IgM+CD21− CD11R1− subpopulation. Noteworthy, sorted IgM+CD21− CD11R1− B-1-like cells from eight-weeks-old pigs spontaneously secreted IgM in vitro. In addition, both non-conventional IgM+CD21− B cell subpopulations, in contrast to conventional IgM+CD21+ B-2 cells, produced anti-S. suis IgM upon toll-like receptor (TLR) stimulation underlining their innate-like characteristics. We furthermore observed that both B-1-like subpopulations secrete S. suis cps 2-binding IgM upon stimulation with T cell-associated factors with highest amounts in IgM+CD21−CD11R1− B-1-like cells even exceeding anti-S. suis IgM levels produced by B-2 cells.

Conclusion

Porcine non-conventional B-1-like cells are a potent source of S. suis-binding IgM indicating a role in immunity during a critical phase of piglet rearing.
GVHD after CAR T-cell therapy post allogeneic hematopoietic cell transplantation — successfully treated by extracorporeal photopheresis
Authors: Farid Kiavasch Mohammad Nejad , Bug Gesine , Schmitt Anita , Lang Fabian , Schubert Maria-Luisa , Haberkorn Uwe , Müller-Tidow Carsten , Dreger Peter , Schmitt Michael
Published: November 2024

Introduction

CAR T-cell therapy is highly effective, but also associated with unique toxicities. Because of the origin of T cells in patients who previously underwent allogeneic hematopoietic cell transplantation (alloHCT), graft-versus-host disease (GVHD) in the post-CAR T-cell setting poses a relevant concern but is only scarcely studied. Potential risk factors and mitigation strategies (from CAR T-cell modifications to clinical management) are yet to be determined.

Methods

Sharing our retrospective experience and a mini-review of the literature, our aim is to better understand the frequency and risk of the potential occurrence of GVHD after CAR T cells, which are most likely underestimated.

Results

Here, we present a cohort of 11 patients with symptoms suggestive of GVHD out of 25 allografted patients treated with CAR T cells, of whom 3 patients (12%) had GVHD most likely triggered by the preceding CAR T-cell treatment. Severe chronic pulmonary GVHD occurred in a patient after CD19-directed CAR T-cell therapy. Extracorporeal photopheresis (ECP) mediated successful long-term control of GVHD without causing relapse of the underlying disease.

Discussion/Conclusion

In conclusion, CD19-directed CAR T-cell therapy seems to be feasible in patients after alloHCT but might comprise the potential risk of triggering GVHD, most likely depending on the T-cell source, donor compatibility, and the specific CAR construct used.
The Pakistan-China FTA: legal challenges and solutions for marine environmental protection
Authors: Khan Asif , Ullah Maseeh
Published: November 2024

Marine ecosystems play a vital role in development, human life, and health, thereby promoting sustainable development. However, due to rapid industrialization and urbanization, as well as intense exploitation of marine resources, among other phenomena, both Pakistani and Chinese marine ecosystems face severe challenges such as pollution, overfishing, and habitat destruction. In particular, the Pakistan-China Free Trade Agreement, which aims to boost economic growth, exacerbates these environmental issues due to the increased trade volume. The purpose of this article is to discuss the challenges of legal standards regulating marine environmental protection within the context of the Pakistan-China Free Trade Agreement. By examining the current state of the mentioned agreement as well as regional judicial practice, the current study demonstrates the need to adopt a number of legal measures, such as including specific teeth provisions within the Free Trade Agreement, establishing a special joint environmental commission, increasing public participation, and boosting national environmental law, in order to reduce the adverse effect on marine ecosystems and properly mitigate such effects with a view to achieving sustainability.
SIFa and its receptors play a possibly stimulatory role during ovarian development of the mud crab Scylla paramamosain
Authors: Chen Sijia , Tang Yiwei , Lu Li , Gong Shaoming , Liu An , Ye Haihui
Published: November 2024

SIFamide is an amidated neuropeptide with a conserved Ser-Ile-Phe structure at its C-terminal, which is crucial in insect courtship, sleep and feeding in insects. However, little information exists regarding its function in crustaceans. This study aimed to identify the cDNA of Sp-SIFa and its two putative receptors (Sp-SIFaR1 and Sp-SIFaR2) in the mud crab Scylla paramamosain. The expression profiles of Sp-SIFa and its receptors signaling were investigated to explore their potential roles. The results indicated that Sp-SIFa was expressed primarily in the nervous tissues and the midgut, and Sp-SIFaR1 was extensively expressed in the eyestalk ganglion, cerebral ganglion, hepatopancreas and the ovary whereas Sp-SIFaR2 was restricted to the eyestalk ganglion and ovary. The Sp-SIFa expression in the cerebral ganglion was significantly increased at the late vitellogenic stage during the ovarian development. The expression patterns of Sp-SIFaR1 and Sp-SIFaR2 in the ovary were similar to Sp-SIFa, indicating a potential function in regulating ovarian development. Subsequently, in vitro and in vivo experiments were performed to further support this hypothesis. The expression of Sp-Vg and Sp-VgR was significantly induced by Sp-SIFa peptide in vitro and in vivo. Moreover, prolonged injection of the Sp-SIFa peptide caused a significant increase in Sp-VgR expression, oocyte diameter and gonadal development index, demonstrating a possible stimulatory effect on ovarian development. In conclusion, our results suggest that Sp-SIFa may regulate ovarian development by promoting Vg biosynthesis and oocyte uptake in the mud crab S. paramamosain.
Transcriptomic analysis reveals pathogenicity mechanisms of Phytophthora capsici in black pepper
Authors: Vijayakumar Saranya , Saraswathy Gayathri G. , Sakuntala Manjula
Published: November 2024

The devastating disease “quick wilt” or “foot rot” is caused by the oomycete Phytophthora capsici Leonian and is affecting the economically significant spice crop black pepper (Piper nigrum L.). The details on the mechanism of interaction of P. capsici with its host black pepper remain poorly understood, hindering efforts to enhance disease resistance. To address this knowledge gap, we conducted an RNA-seq analysis to investigate the gene expression profile of P. capsici infecting black pepper. Comparative transcriptome analysis between axenic culture, and early and late infection stages of P. capsici revealed a substantial number of differentially expressed genes. Our findings demonstrate the induction of metabolic pathways, signaling cascades, and crucial pathogenicity-related processes during infection of black pepper by P. capsici. Specifically, we observed orchestrated expression of cell wall-degrading enzymes, effectors, and, detoxifying transporters at different infection time points, implicating their roles in pathogenicity. The expression patterns of key pathogenicity-associated genes, including effectors, were validated using reverse transcription quantitative real-time PCR. The effectiveness of agroinfiltration-mediated transient expression in black pepper for functional studies of effectors is also demonstrated in this study. Overall, this study establishes a strong foundation for further studies elucidating the pathogenic mechanisms employed by P. capsici infecting black pepper and for developing effective disease management strategies. Future investigations building upon these findings are essential for advancing our understanding of this pathosystem and for implementing targeted approaches to mitigate black pepper foot rot.
Reorganized brain functional network topology in stable and progressive mild cognitive impairment
Authors: Xue Chen , Zheng Darui , Ruan Yiming , Cao Xuan , Zhang Xulian , Qi Wenzhang , Yuan Qianqian , Liang Xuhong , Huang Qingling
Published: November 2024

AIM

Mild cognitive impairment (MCI) includes two distinct subtypes, namely progressive MCI (pMCI) and stable MCI (sMCI). The objective of this study was to identify the topological reorganization of brain functional networks in patients with pMCI and sMCI.

Methods

Resting-state functional magnetic resonance imaging (rs-fMRI) was applied to patients with pMCI, sMCI and healthy controls. Graph theory was applied to study the topological characteristics of the brain’s functional networks, examining global and nodal metrics, modularity, and rich-club organization. Analysis of covariance and two sample t-tests were applied to assess differences in topological attributes between patient groups, alongside correlation analysis, which examined the value of changing topological attributes in predicting various clinical outcomes.

Results

Significant differences between each group with regard to network metrics were observed. These included clustering coefficients and small-worldness. At the nodal level, several nodes with an abnormal degree centrality and nodal efficiency were detected. In rich club, pMCI and sMCI patients showed declined connectivity compared with HC. Significant differences were observed in the intra- and inter-module connections among the three groups. Particularly noteworthy was the irreplaceable role of the cerebellar module in network interactions.

Conclusion

Our study revealed significant differences in network topological properties among sMCI, pMCI and HC patients, which were significantly correlated with cognitive function. Most notably, the cerebellar module played a crucial role in the overall network interactions. In conclusion, these findings could aid in the development of imaging markers used to expedite diagnosis and intervention prior to Alzheimer’s disease onset.
Silymarin administration after cerebral ischemia improves survival of obese mice by increasing cortical BDNF and IGF1 levels
Authors: Rodríguez-Cortés Yesica María , Ramírez-Carreto Ricardo Jair , Rodríguez-Barrena Julia Isabel , Salazar-Castro Marelly , Chavarría Anahí
Published: November 2024

Background

Obesity is associated with a systemic inflammatory state that contributes to neuroinflammation and increases the risk of stroke at an early age. Stroke is the third leading cause of death worldwide and the leading cause of permanent disability. This work aimed to assess whether obesity-induced neuroinflammation can be a prognostic stroke factor that can be improved with oral administration of silymarin, an anti-inflammatory and neuroprotective drug.

Methods

Male C57/Bl6 mice were used to establish an obesity model through a high-fat diet (HFD) for 12 weeks. Cerebral ischemia was performed with photothrombosis in the left motor cortex at the end of the diet. Following the induction of ischemia, silymarin (100 mg/kg) was administered orally for 14 days. Levels of pro-inflammatory (IL1β, TNFα, and MCP1) and anti-inflammatory markers (IL4, IL10), neurotrophic factors (IGF1, BDNF), and CX3CL1 were assessed in the cortex and striatum using ELISA.

Results

Mice on the HFD gained significantly more weight than control subjects and exhibited altered glucose metabolism, which was improved after silymarin treatment. The survival rate was significantly lower in HFD mice (52.2%) compared to control mice (86%). Silymarin treatment improved survival in both ischemic groups (non-diet control: 95.7%, HFD: 78.3%). Silymarin raised cortical TNFα, IL4, IL10, IGF1, BDNF, and CX3CL1 levels in the HFD group with stroke, while the striatum did not present relevant differences.

Conclusion

Our findings suggest that silymarin improves glucose metabolism, possibly impacting post-stroke survival in obese mice. The increased levels of neurotrophic factors BDNF and IGF1, along with microglial regulatory factor CX3CL1, may contribute to the improved survival observed. These results indicate that silymarin could be a potential therapeutic option for managing neuroinflammation and enhancing post-stroke outcomes in obese individuals.
Maintenance of a central high frequency synapse in the absence of synaptic activity
Authors: Lessle Sascha , Ebbers Lena , Dörflinger Yvette , Hoppe Simone , Kaiser Michaela , Nothwang Hans Gerd , Körber Christoph
Published: November 2024

Activity has long been considered essential for circuit formation and maintenance. This view has recently been challenged by proper synaptogenesis and only mildly affected synapse maintenance in the absence of synaptic activity in forebrain neurons. Here, we investigated whether synaptic activity is necessary for the development and maintenance of the calyx of Held synapse. This giant synapse located in the auditory brainstem is highly specialized to maintain high frequency, high-fidelity synaptic transmission for prolonged times and thus shows particularly high synaptic activity. We expressed the protease tetanus toxin light chain (TeNT) exclusively in bushy cells of the ventral cochlear nucleus (VCN) of juvenile mice. Since globular bushy cells give rise to the calyx of Held, expression of TeNT in these cells specifically abolished synaptic transmission at the calyx without impairing general functionality of the central auditory system. Calyces lacked synaptic activity after two weeks of TeNT expression. However, this did not lead to major changes in presynaptic morphology, the number of active zones (AZs) or the composition of postsynaptic AMPA-type glutamate receptors (GluAs). Moreover, the fenestration of the calyx of Held, a hallmark of structural maturation, occurred normally. We thus show that the maintenance of a specialized high frequency synapse in the auditory brainstem occurs in a hardwired, probably genetically encoded, manner with little dependence on synaptic activity.
Changing the view on spastic movement disorder management to improve active movement competence in the upper motor neuron syndrome: a clinical perspective
Authors: Wissel Jörg , Hernandez Franco Jorge
Published: November 2024

It is common in clinical practice to evaluate active movement in spastic movement disorders (SMDs) associated with the upper motor neuron syndrome in terms of resistance to passive movement in the rest position, with the assumption that this may reflect motor control when the patient is in active motion. In addition, the definition of spasticity as a velocity-dependent resistance to passive movement does not account for the impact of abnormal muscle synergies (synkinesia), on active motion of upper and lower limbs in SMDs. In this article, we put forward our theory that synkinetic movement patterns are controlled by activation from spinal afferents and inhibition from the cortex, and become disturbed following a loss of inhibition and change to spinal afferents following damage to the corticospinal tract. In this regard, we propose a change in the focus from passive to active function at the evaluation stage of the SMD management plan, and a new treatment approach to modulate muscle synergies with botulinum neurotoxin type A therapy.
Accuracy of diagnostic tests for perilymphatic fistula: protocol for a systematic review
Authors: Situkho Maksym , Ikezono Tetsuo , Myhrum Marte , Rødvik Arne Kirkhorn , Maeda Yukihide , Matsuda Han , Sawada Masafumi , Jablonski Greg Eigner
Published: November 2024

Perilymphatic fistula (PLF) is a challenging inner ear condition, characterized by the abnormal connection between inner and middle ear and subsequent leakage of inner ear liquid (perilymph) into the middle ear. Early surgical intervention for PLF might lead to favorable audiological and vestibular outcomes. The conventional reference standard of PLF detection is the intraoperative visualization of perilymph leakage during explorative tympanotomy or endoscopic inspection; the specificity and sensitivity of this method is unknown. Systematic reviews assessing the accuracy of diagnostic tests for PLF are not available.

Objective

To systematically review the literature for qualitative evidence exploring the diagnostic tests for the PLF diagnosis. The proposed systematic review will answer the following question: What is the accuracy of diagnostic tests in detecting perilymphatic fistula in humans?

Methods

Eligibility criteria: original peer-reviewed articles regarding studies on humans of any age containing data with diagnostic test accuracy estimation (sensitivity and specificity) for PLF diagnosis or in which diagnostic test accuracy could be calculated based on data provided, without language, study design or study date limits. MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Scopus, and Web of Science will be searched for eligible articles. Additional manual searches will be performed. Covidence software will be used for title and abstract screening, full text review and data extraction. The risk of bias assessment will be conducted using the Quality Assessment of Diagnostic Test Accuracy 2 (QUADAS-2) tool. If two or more high-quality articles evaluating the same diagnostic test will be identified, their findings will be quantitatively synthesized; if a quantitative synthesis is not feasible, the results will be described in a narrative summary. Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework will be used to evaluate evidence strength. Study funded by Oslo University Hospital.
Exploration of the value of concurrent chemotherapy for T2N1 nasopharyngeal carcinoma under intensity modulated radiotherapy mode
Authors: Liao Kai , Zhang Jian , Qiu Wenze , Zheng Ronghui
Published: November 2024

Problem

In the era of intensity-modulated radiation therapy (IMRT), the status of concurrent chemoradiotherapy(CCRT) for stage II nasopharyngeal carcinoma(NPC), particularly for patients in T2N1 subtype, remains controversial nowadays.

Aim

This study exclusively aims to explore the value of concurrent chemotherapy in the treatment of T2N1 NPC under IMRT mode.

Methods

A retrospective analysis was conducted on 218 cases of T2N1 NPC patients treated at our hospital from January 2015 to December 2020, comprising 75 cases treated with IMRT and 143 cases treated with CCRT. The study compared therapeutic outcomes and side effects between the two groups.

Results

The 5-year progression-free survival (PFS), overall survival (OS), locoregional relapse-free survival (LRRFS) and,distant metastasis-free survival (DMFS) estimated by the K-M method for the IMRT vs. CCRT groups were 86.1% vs. 85.1%,89.3% vs. 87.9%, 95.9% vs. 94.9%,and 90.2% vs. 89.1%, respectively, with no statistically significant differences (Log-rank P>0.05 for all comparisons). Cox regression analysis identified Epstein-Barr virus (EBV) DNA copy level (≥1000 vs. <1000 copies/ml)(the cutoff value was determined through the ROC curve), lymph node necrosis (yes vs. no) and extra-nodal extension (yes vs. no) as independent prognostic factors for PFS(P<0.05 for all comparisons). Subgroup analysis indicated an interaction effect between lymph node necrosis (yes vs. no) and treatment modality (IMRT vs. CCRT) regarding PFS (P for interaction<0.05). In the subgroup with lymph node necrosis, IMRT compared to CCRT had a poorer prognosis (HR: 1.85,95% CI: 1.02-3.50). CCRT was noted to increase acute hematological, gastrointestinal and other toxicities.

Conclusions

This study provides a reference for clinical treatment decisions in T2N1 NPC. For the entire population of T2N1 NPC, the therapeutic effects of IMRT and CCRT are comparable, with increased acute toxicities in the latter. However, for patients with EBV-DNA copy level ≥1000 copies/ml, lymph node necrosis and extra-nodal extension, CCRT may be considered as appropriate. Particularly, patients with lymph node necrosis may be potential beneficiaries for CCRT.
Case report: Metastatic endocrine mucin-producing sweat gland carcinoma with features of mucinous carcinoma
Authors: Sun Yuehua , Liu Yingchun , Li Chuntao , Zhang Xiaodong , Yin Lu , Niu Jun
Published: November 2024

Endocrine mucin-producing sweat gland carcinoma is a rare neoplasm of the skin appendages. The tumor typically exhibits slow growth and rarely metastasizes to distant sites. Herein, we report a case of a 77-year-old male who presented with a skin lesion on the right anterior chest wall 23 years ago. Fifteen years later, surgical excision was performed, and the pathological diagnosis was endocrine mucin-producing sweat gland carcinomas. However, the histopathological examination revealed a coexistence of endocrine mucin-producing sweat gland carcinomas and mucinous carcinoma components. Over the past 2 years, the patient developed lymph node metastasis in the right axilla, local recurrence on the right chest wall, and distant skin metastasis. The histopathological type of the lymph node metastasis was consistent with the primary tumor, while the recurrent and skin metastatic lesions exhibited mucinous carcinoma. To our knowledge, this is the first reported case of endocrine mucin-producing sweat gland carcinoma with distant skin metastasis, characterized by two distinct carcinoma components in the histopathological morphology.
Efficacy and safety of angiogenesis inhibitors combined with poly ADP ribose polymerase inhibitors in the maintenance treatment of advanced ovarian cancer: a meta-analysis
Authors: Huang Renming , Ji Feng , Huang Leyi , Qin Yueying , Liang Zhiyu , Huang Miaoyan , Li Chunyan , Ban Jian
Published: November 2024

Introduction

This meta-analysis was performed to evaluate the efficacy and safety of angiogenesis inhibitors (Ais) combined with poly ADP ribose polymerase inhibitors (PARPi) in the maintenance treatment of advanced ovarian cancer (OC).

Materials and methods

A systematic search was conducted in four databases (Pubmed, Embase, Web of Science, and Cochrane) for articles published from the inception of the databases until January 15, 2024. The focus of the search was on articles investigating the combination of Ais with PARPi in the maintenance treatment of ovarian cancer. Meta-analyses were conducted to assess the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and the risk of Grade ≥ 3 adverse events (Grade≥ 3 AEs).

Results

Totally nine studies were included for meta-analysis. The overall pooled ORR of Ais combined with PARPi was 57% (95% CI, 35% to 77%). Subgroup analyses showed that the ORR for patients with platinum-resistant recurrent ovarian cancer, platinum-sensitive recurrent ovarian cancer and newly diagnosed advanced ovarian cancer were 30% (95% CI, 12% to 52%), 70% (95% CI, 61% to 78%) and 59% (95% CI, 55% to 63%), respectively. The median PFS was 5.8 months (95% CI, 5.3 to 7.1), 12.4 months (95% CI, 10.6 to 13.2) and 22.4 months (95% CI, 21.5 to 24.2), respectively. The median OS was 15.5 months (95% CI, 12.3 to 24.8), 40.8 months (95% CI, 33.4 to 45.2) and 56.3 months (95% CI, 49.0 to 62.0), respectively. The rate Grade≥ 3 TRAEs rate was found to be 0.22 (95% CI, 0.13 to 0.33).

Conclusions

Our results confirmed that PARPi plus Ais was a feasible and safe option for the maintenance treatment of advanced ovarian cancer. The combination therapy should be recommended as the first-line maintenance treatment for patients with advanced ovarian cancer. PARPi plus Ais yielded more favorable oncological prognosis for patients with platinum-sensitive recurrent ovarian cancer, compared to patients with platinum-resistant recurrent ovarian cancer.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024543590, identifier CRD42024543590.
Mindfulness, character, and workplace happiness: the moderating role of baseline levels of employee wellbeing
Authors: Monzani Lucas , Ruiz Pardo Ana , Bruschetto Sonja , Ellis Cassandra , Escartin Jordi
Published: November 2024

Following the logic of the “happy-productive worker” hypothesis, organizations have been increasingly interested in new ways to elicit employee wellbeing. Consequently, research on mindfulness in work contexts has been burgeoning in recent years, as both conceptual and empirical reviews substantiated its importance as a cost-effective approach to promoting employee wellbeing. The purpose of the present study was to investigate whether employee happiness extends or transcends the conventional notions of employee wellbeing. More specifically, we invoke the positive psychology literature to argue that (a) employee happiness is related but distinct from employee wellbeing and (b) that initial levels of employee wellbeing might moderate the effect of mindfulness-based interventions. We conducted a secondary analysis of a publicly available dataset to test our predictions: focusing on 35 healthcare professionals from a healthcare organization in Barcelona, Spain. More precisely, employing a multivariate hierarchical regression, we compared if the incremental effect of an eight-week mindfulness-based strength intervention (MBSI) over a Mindfulness-based intervention (MBI) might be moderated by employees' initial levels before the intervention starts. Our results supported a moderating effect of employees' initial psychological wellbeing on a MBSI versus MBI. Implications for theory and practice are discussed.
The mutually reinforcing dynamics between pain and stress: mechanisms, impacts and management strategies
Authors: Aboushaar Nour , Serrano Natalia
Published: November 2024

While distinct, pain and stress share complex biological and psychological mechanisms that—despite their protective functions—can lead to clinically maladaptive changes requiring therapeutic intervention when they recur or persist. Recognized as “worldwide epidemics” of modern life, both conditions significantly affect an individual's quality of life, functioning, and well-being; without timely intervention, they can become chronic, leading to substantial economic costs via healthcare expenses, lost wages, and reduced productivity. Evidence suggests that pain and stress not only feed into but exacerbate each other through a “vicious cycle,” driven by overlapping physiological, cognitive, and social mechanisms, indicating mutually reinforcing dynamics between pain and stress. In this review, we highlight the importance of recognizing the overlapping mechanisms that promote the persistence of pain and stress: (1) key physiological processes like maladaptive neuroplasticity, neuroendocrine dysfunction, and chronic inflammation; (2) cognitive and behavioral patterns such as fear avoidance, hypervigilance, and catastrophizing; along with (3) social, lifestyle, and environmental influences, such as socioeconomic status, lack of social support, and lifestyle choices. Through a case study, we illustrate the real-world implications of this vicious cycle perpetuating both conditions. We call for a paradigm shift in pain and stress management, advocating for a holistic management strategy encompassing pharmacological, psychological, and lifestyle interventions that address the underlying biopsychosocial factors. By fostering greater awareness among primary care practitioners and healthcare professionals, it is possible to better support individuals in breaking the cycle of pain and stress, thereby enhancing their quality of life and overall well-being.
Protocol of REACH-01: a single-arm, open label, prospective study of HAIC sequential TAE combined with tislelizumab and surufatinib in unresectable intrahepatic cholangiocarcinoma
Authors: Li Kang-shuai , Liu Yi , Zhang Tie-zhong , Xu Yun-fei , Zhang Zong-li
Published: November 2024

Introduction

Gemcitabine and cisplatin remain the cornerstone for the treatment of advanced or unresectable biliary tract cancers, but the incidence rate of the grade 3 or 4 toxic effects is high (70.7%). In recent years, significant progress has been achieved in the systemic treatment of cholangiocarcinoma with immune checkpoint inhibitors (ICIs), targeted therapy, and hepatic artery infusion chemotherapy (HAIC). HAIC may elevate the local drug concentration in the liver to 10–100 times the drug plasma concentration; therefore, it may enhance tumor cytotoxicity while minimizing systemic adverse effects. HAIC combined with immunotherapy and targeted therapy resulted in acceptable tumor responses and tolerable toxic effects in the treatment of hepatocellular carcinoma (HCC). However, whether this combination strategy can benefit patients with unresectable intrahepatic cholangiocarcinoma remains unclear.

Methods and Analysis

We describe a single-arm, open label, prospective clinical trial of HAIC sequential transcatheter arterial embolization (TAE) combined with tislelizumab and surufatinib in patients with unresectable intrahepatic cholangiocarcinoma. TAE + HAIC was performed at an interval of at least 3 weeks, and oxaliplatin (85 mg/m2) and rituximab (3 mg/m2) were infused. TAE was performed using undrugged microspheres. Tislelizumab was infused every 3 weeks and surufatinib was administered orally once a day, with 3-5 capsules (50 mg/capsule) each time. We plan to enroll 28 participants in this study. The primary study endpoint was objective response rate (ORR). The secondary endpoints were progression-free survival (PFS), conversion to surgical resection rate, overall survival (OS), 1-year OS rate, disease control rate (DCR), quality of life (QoL), and incidence of adverse events.

Trial registration number

NCT06239532.
Maslinic acid induces autophagy and ferroptosis via transcriptomic and metabolomic reprogramming in prostate cancer cells
Authors: Hu Fen , Sun Yuxi , Zhang Yunfeng , Chen Jiaxin , Deng Yingzi , Li Yifei , Li Ruobing , Zhang Juan , Liang Yongping , Liu Yan , Wang Shuqing , Li Mi , Zhao Lina , Liu Yuwei , Gong Xiaodong , Cai Haifeng , Gu Shouqin
Published: November 2024

Prostate cancer has the second highest incidence among male malignancies. Only a few studies exist on the inhibitory effects of maslinic acid (MA) on prostate cancer. Herein we found that MA inhibits prostate cancer cell proliferation by decreasing CDK2, CDK4, and CDK6 expression and concurrently increasing p27, Rb, p-Rb expression. Further, MA was observed to induce prostate cancer cell autophagy by increasing the expression of p53, p-p53, ULK1, Beclin1, Atg7, and Atg5 and the ratio of LC3-II/I and concurrently decreasing the expression of ERK1/2 and mTOR. In addition, MA induced RM-1 cell ferroptosis by regulating glutathione, glutamate, and oxidized glutathione concentrations, inhibiting SLC7A11 activity, and downregulating GPX4 expression. Integrated metabolome and transcriptome analysis led to the identification of key pathways (e.g., pathways in cancer and glutathione metabolism). Real-time quantitative PCR confirmed that MA regulates the expression of ABCA1, JUN, and NFKBIA. In vivo, we demonstrated that 50 mg/kg MA significantly inhibited the growth of tumors established using RM-1 cells. To summarize, we report that MA inhibits prostate cancer cell growth both in vitro and in vivo by inducing autophagy and ferroptosis via transcriptomic and metabolomic reprogramming.
Comparative bactericidal activity of four macrolides alone and combined with rifampicin or doxycycline against Rhodococcus equi at concentrations achievable in foals
Authors: Huguet Anne-Sophie , Gourbeyre Ophélie , Bernand Agathe , Philibert Charline , Bousquet-Melou Alain , Lallemand Elodie A. , Ferran Aude A.
Published: November 2024

Introduction

Rhodococcus equi causes life-threatening respiratory disease in foals. The standard treatment typically involves a combination of rifampicin and a macrolide antibiotic. Although previous studies have demonstrated the in vitro activity of these antibiotics against Rhodococcus equi, the tested concentrations often do not reflect those achievable in foals.

Material and Methods

Therefore, this study was performed to evaluate the in vitro bactericidal activity of rifampicin, doxycycline, and four macrolides (clarithromycin, azithromycin, gamithromycin and tulathromycin) individually and in combination, at concentrations observed at the target site of infection in foals. Additionally, we investigated the efficacy of these antibiotics at different pH levels to replicate the conditions in the pulmonary epithelial lining fluid and within macrophages, where R. equi can reside. We assessed the activity of antibiotics against a virulent strain of R. equi by determining the minimum inhibitory concentration (MIC) and performing checkerboard and time-kill curve assays with drugs both alone and in combination.

Results

Time-kill curves with rifampicin or doxycycline demonstrated a reduction in R. equi counts by more than 3 log10 CFU/mL. Among the macrolides, tulathromycin was ineffective, while clarithromycin achieved bacterial elimination within 24 h under both extracellular and intracellular conditions. Gamithromycin and azithromycin exhibited bactericidal activity only in extracellular conditions, with no effect on the bacteria at pH 5.8. The checkerboard assay did not reveal any strong synergistic or antagonistic effects for rifampicin or doxycycline when combined with macrolides. In time-kill curves performed with maximal local concentrations achievable in foals, the combinations of rifampicin or doxycycline with macrolides did not increase the bacterial killing rate compared with the drugs alone, except for the combination of rifampicin with azithromycin, which showed slightly faster activity. However, the lower concentrations of doxycycline and clarithromycin that might be present 24 h after treatment in foals were effective in killing bacteria under intracellular conditions only when used in combination, and not when used alone.

Conclusion

Our study suggests that clarithromycin can be used either alone or with doxycycline and that its use in combination with rifampicin should be reconsidered. Nevertheless, further studies are required to assess the clinical efficacy and potential side effects of doxycycline in foals.
Impacts of elevated CO2 and partial defoliation on mineral element composition in rice
Authors: Gao Bo , Hu Shaowu , Zhou Mingyuan , Jing Liquan , Wang Yunxia , Zhu Jianguo , Sun Xingxing , Wang Kai , Wang Yulong , Yang Lianxin
Published: November 2024

Introduction

This study explores how elevated CO2 concentration may alter the source-sink dynamics in rice by providing additional carbon for photosynthesis, thereby affecting nutrient absorption and distribution.

Methods

A free-air CO2 enrichment experiment was conducted on a japonica cultivar Wuyunjing 27 in 2017 and 2018 growing seasons. The plants were exposed to ambient and elevated CO2 level (increased by 200 μmol·mol-1) and two source-sink manipulation treatments (control with no leaf cutting and cutting off the top three leaves at heading).

Results

The elevated CO2 significantly increased the above-ground biomass and the straw non-structural carbohydrate concentration by an average of 19.3% and 12.5%, respectively. Significant changes in the concentrations of N, S, Fe, and Zn in straw were noted under elevated CO2, with average decreases by 7.1, 7.2, 11.6, and 10.1%, respectively. The exposure to elevated CO2 significantly enhanced the elements accumulation, yet it had minimal impact on their distribution across different organs. When compared to intact rice, removing the top three leaves at heading reduced the above-ground biomass by 36.8% and the straw non-structural carbohydrate content by 44.8%. Leaf-cutting generally increased the concentration of elements in stem, leaf, and grain, likely due to a concentration effect from reduced biomass and carbohydrate accumulation. Leaf-cutting reduced element accumulation and shifted element allocation in rice organs. It increased the proportion of elements in stems while reduced their presence in leaves and grains.

Discussion

Our study suggests that a dilution effect may cause a decrease in mineral elements concentrations under elevated CO2 because of the increase in biomass and carbohydrates.
The structural relationship of job stress, job satisfaction, organizational commitment, and turnover intention among youth sports education leaders in Korea
Authors: Jung Myung Kyu , Jung Tae Gyeom , Jeon Min Woo , Lee Ji Hae
Published: November 2024

Introduction

This paper is a study aimed at providing insights for developing effective human resource management strategies suitable for Korean youth sports education facilities, by elucidating the multifaceted relationships among job stress, job satisfaction, organizational commitment, and turnover intention. Through the research, it was academically suggested that the relationships among job stress, job satisfaction, organizational commitment, and turnover intention of Korean youth sports education facility workers could be structurally and complementarily manifested. To fulfill this objective, data were gathered using snowball sampling from Sports leaders who have experience or are engaged in sports education facilities for youth in Korea as of 23 years. A total of 384 responses were analyzed using frequency, technical statistics, and confirmatory factor, reliability, correlation, and structural equation model analyses.

Results

Through these analyses, this study found that job Stress, job satisfaction, organizational commitment were significant as both direct and indirect influences on turnover Intention. Intervention strategies should focus on fostering the positive emotions that stem from Intermediation, mitigation, and improvement of job stress.
Impact of physical activity on anxiety among university students: a moderated mediation model
Authors: Qin Tianci , Chen Ping , Wang Jiale , Dong Junwei , Zhang Kai
Published: November 2024

Physical activity among university students significantly influences anxiety, yet the underlying mechanisms require further exploration. This study examines mental toughness as a mediator and social support as a moderator to elucidate these relationships.

Methods

Using a cross-sectional design, convenient sampling was employed to select 997 first to fourth-year students from Jishou University for a self-reported survey. Measures included assessments of physical activity, mental toughness, social support, anxiety, and basic demographic variables. Descriptive statistics, correlations, and a moderated mediation model were conducted.

Results

Physical activity was significantly negatively correlated with anxiety and positively correlated with mental toughness. Mental toughness was significantly negatively correlated with anxiety, mediating the relationship between physical activity and anxiety to a certain extent. Social support moderated the latter part of the mediated model pathways.

Conclusion

Physical activity negatively correlates with anxiety among university students. Mental toughness mediates the relationship between physical activity and anxiety, while social support moderates the latter stages of this mediated model (mental toughness → anxiety).