bluuebunny/crossref_metadata_2025 huggingface dataset:
Presence and (dis)connectedness – the influence of smartphones usage on human–nature and human–human interactions in outdoor studies
Authors: van Kraalingen Imre , Beames Simon
Published: May 2024

Interactions between students and nature and students and their peers are central to learning processes in outdoor studies programs. This paper draws on symbolic interactionist social theory to interpret participants’ experiences of smartphone usage and its impact on human–nature and human–human interactions. The findings are derived from a collective case study using semi-structured interviews with educators and focus group interviews with students enrolled in outdoor studies programs in Norway. Two primary themes were identified through reflexive thematic analysis: perceptions of nature and attentiveness to peers. Each of these themes illustrates the fluctuating presence and (dis) connectedness of students and the implications of this for learning out-of-doors. On the one hand, the findings suggest that the use of smartphones reduces students’ sensory perception of nature and their attentiveness to interactions with their peers. On the other hand, smartphones and their access to online networks can contribute to the continuity of learning experiences between indoor and outdoor learning, as well as beyond the formal learning environment. Taken together, this inquiry offers new insights into the challenges of tertiary level teaching and learning outdoors in spaces that are mediated (at times) by interactions with smartphones and associated media infrastructures.
A clinicopathological study of non-functioning pituitary neuroendocrine tumours using the World Health Organization 2022 classification
Authors: Woo Chariene Shao-Lin , Ho Ronnie Siu-Lun , Ho Grace , Lau Hoi-To , Fong Carol Ho-Yi , Chang Johnny Yau-Cheung , Leung Eunice Ka-Hong , Tang Lawrence Chi-Kin , Ma Ivan Kwok-Ming , Lee Alan Chun-Hong , Lui David Tak-Wai , Woo Yu-Cho , Chow Wing-Sun , Leung Gilberto Ka-Kit , Tan Kathryn Choon-Beng , Lam Karen Siu-Ling , Lee Chi-Ho
Published: May 2024

Background

The 2022 World Health Organization (WHO) classification of pituitary neuroendocrine tumour (PitNET) supersedes the previous one in 2017 and further consolidates the role of transcription factors (TF) in the diagnosis of PitNET. Here, we investigated the clinical utility of the 2022 WHO classification, as compared to that of 2017, in a cohort of patients with non-functioning PitNET (NF-PitNET).

Methods

A total of 113 NF-PitNET patients who underwent resection between 2010 and 2021, and had follow-up at Queen Mary Hospital, Hong Kong, were recruited. Surgical specimens were re-stained for the three TF: steroidogenic factor (SF-1), T-box family member TBX19 (TPIT) and POU class 1 homeobox 1 (Pit-1). The associations of different NF-PitNET subtypes with tumour-related outcomes were evaluated by logistic and Cox regression analyses.

Results

Based on the 2022 WHO classification, the majority of NF-PitNET was SF-1-lineage tumours (58.4%), followed by TPIT-lineage tumours (18.6%), tumours with no distinct lineage (16.8%) and Pit-1-lineage tumours (6.2%). Despite fewer entities than the 2017 classification, significant differences in disease-free survival were present amongst these four subtypes (Log-rank test p=0.003), specifically between SF-1-lineage PitNET and PitNET without distinct lineage (Log-rank test p<0.001). In multivariable Cox regression analysis, the subtype of PitNET without distinct lineage (HR 3.02, 95% CI 1.28-7.16, p=0.012), together with tumour volume (HR 1.04, 95% CI 1.01-1.07, p=0.017), were independent predictors of a composite of residual or recurrent disease.

Conclusion

The 2022 WHO classification of PitNET is a clinically useful TF and lineage-based system for subtyping NF-PitNET with different tumour behaviour and prognosis.
How did ancient human activities influence the properties and development of soil?—a case study of the Yangshao Village cultural relic site, Henan Province
Authors: Zha Lisi , Wang Wenjing , Zhong Junhong , Su Yiqi , Chang Dandan
Published: May 2024

Introduction: What were the effects of paleoanthropogenic activities on the physicochemical properties and degree of the development of soil? To search for this answer, we can not only understand the different types of ancient human activities but also explore the intensity and characteristics of the activities.

Methods: In this study, soil samples from different soil layers and two profiles in the Yangshao Village cultural site in Henan Province were collected. Their physicochemical properties and the sporophyte phyllosilicates they contain were analyzed and compared.

Results: We found that the paleoanthropogenic activities started in the relatively low-lying area, in which the slash-and-burn activities resulted in the soil being filled with intrusions such as charcoal debris and ceramic shards. At the same time, the coarse-grained matter was affected by the plowing activities and mostly decomposed into fine particles, and the content of clay particles reached an extreme value. The total nitrogen, phosphorus, and calcium carbonate content exceeded the average value of the natural profile, indicating that ancient humans had used human and animal feces to a certain extent to restore the fertility of arable land.

Discussion: Overall, ancient human activities hindered the development of the soil, especially the ground created due to habitation activities. From the type and content of clay minerals, it could be seen that the soil in this layer has been transported from other places, has a high content of clay particles, and has experienced fire baking. It was assumed that the ground was used to cover the grain or bury the garbage and lay with clay in order to achieve the effect of sealing. As a result, the soil voids and structure had been damaged to some extent, which prevented the downward leaching or precipitation of soil particles and minerals to a certain extent, thus affecting soil development.
Male chicks play more than females – sex differences in chicken play ontogeny
Authors: Oscarsson Rebecca , Jensen Per
Published: May 2024

Play indicates positive affective states and can therefore potentially be used as an indicator of positive welfare. Sex differences in play has been reported in many mammalian species, but in birds, this is still to be explored. It is known that young chickens perform play behavior during their early ontogeny, but potential sex differences have not previously been addressed. Therefore, we aimed to investigate potential sex effects on play ontogeny in young chickens, by comparing play occurrence in young males and females of a commercial hybrid of White Leghorn. Eighteen chicks of each sex were hatched in the same incubator and then housed in sex-separated groups. Six groups of three chicks each were randomly created for each sex, and the same three chicks were then moved to enriched play arenas twice per week, from day 6 until day 53 post hatch. The frequency of different play behaviors, categorized as locomotor play, social play and object play were recorded during 30 min on each observation day. Each group of three birds constituted the independent statistical replicate. Males played significantly more than females, due to more social and object play, whereas for locomotor play, no difference was found between the sexes. In conclusion, clear sex differences in play in chickens was demonstrated, and this may be linked to the highly sexually dimorphic behavior of adult cockerels and hens. Further research is needed to elucidate the relationships between type and frequency of play in chicks and later behavior as adults.
Deciphering the role of apoptosis signature on the immune dynamics and therapeutic prognosis in breast cancer: Implication for immunotherapy
Authors: Yu Yunfang , Jia Xueyuan , Chen Sunyu , Lai Zijia , Deng Heran , Mo Yuqian , Xie Xinxin , Wang Zehua , Lin Ruichong , Ouyang Wenhao , Yao Herui , Wu Jiannan
Published: May 2024

Background: In breast cancer oncogenesis, the precise role of cell apoptosis holds untapped potential for prognostic and therapeutic insights. Thus, it is important to develop a model predicated for breast cancer patients’ prognosis and immunotherapy response based on apoptosis-related signature.

Methods: Our approach involved leveraging a training dataset from The Cancer Genome Atlas (TCGA) to construct an apoptosis-related gene prognostic model. The model’s validity was then tested across several cohorts, including METABRIC, Sun Yat-sen Memorial Hospital Sun Yat-sen University (SYSMH), and IMvigor210, to ensure its applicability and robustness across different patient demographics and treatment scenarios. Furthermore, we utilized Quantitative Polymerase Chain Reaction (qPCR) analysis to explore the expression patterns of these model genes in breast cancer cell lines compared to immortalized mammary epithelial cell lines, aiming to confirm their differential expression and underline their significance in the context of breast cancer.

Results: Through the development and validation of our prognostic model based on seven apoptosis-related genes, we have demonstrated its substantial predictive power for the survival outcomes of breast cancer patients. The model effectively stratified patients into high and low-risk categories, with high-risk patients showing significantly poorer overall survival in the training cohort and across all validation cohorts. Importantly, qPCR analysis confirmed that the genes constituting our model indeed exhibit differential expression in breast cancer cell lines when contrasted with immortalized mammary epithelial cell lines.

Conclusion: Our study establishes a groundbreaking prognostic model using apoptosis-related genes to enhance the precision of breast cancer prognosis and treatment, particularly in predicting immunotherapy response.
A global view of T cell metabolism in systemic lupus erythematosus
Authors: Goetz Andrew , Cagmat Joy , Brusko Maigan , Brusko Todd M. , Rushin Anna , Merritt Matthew , Garrett Timothy , Morel Laurence , Dixit Purushottam
Published: May 2024

Impaired metabolism is recognized as an important contributor to pathogenicity of T cells in Systemic Lupus Erythematosus (SLE). Over the last two decades, we have acquired significant knowledge about the signaling and transcriptomic programs related to metabolic rewiring in healthy and SLE T cells. However, our understanding of metabolic network activity derives largely from studying metabolic pathways in isolation. Here, we argue that enzymatic activities are necessarily coupled through mass and energy balance constraints with in-built network-wide dependencies and compensation mechanisms. Therefore, metabolic rewiring of T cells in SLE must be understood in the context of the entire network, including changes in metabolic demands such as shifts in biomass composition and cytokine secretion rates as well as changes in uptake/excretion rates of multiple nutrients and waste products. As a way forward, we suggest cell physiology experiments and integration of orthogonal metabolic measurements through computational modeling towards a comprehensive understanding of T cell metabolism in lupus.
Sustainable high-strength alkali-activated slag concrete is achieved by recycling emulsified waste cooking oil
Authors: Huang Jinguang , Huo Yanlin , Su Qunshan , Lu Dong , Wu Yuanchao , Dong Xinhong , Gao Yang
Published: May 2024

To mitigate the shrinkage of high-strength alkali-activated slag concrete (AASC), this paper introduces emulsified cooking oil (ECO) and emulsified waste cooking oil (EWCO) into the AASC system. The effects of admixing ECO and EWCO on the compressive strength, drying shrinkage, autogenous shrinkage, carbonation, and sulfuric acid resistance of the AASC are systematically explored. The optimization mechanism is also proposed based on the surface tension and microstructural analysis. The experimental results show that the admixing ECO and EWCO slightly reduce the compressive strength of the AASC by 7.8%. Interestingly, the admixing ECO and EWCO significantly reduce the drying shrinkage and autogenous shrinkage, simultaneously improving the resistance to carbonation and sulfuric acid of the AASC. Specifically, the introduction of 2 wt.% ECO and EWCO can reduce the autogenous shrinkage of the AASC by 66.7% and 41.0%, respectively. Microstructural observations reveal that the addition of ECO and EWCO can reduce the internal surface tension of the AASC, improve the transport and diffusion of the pore solution, and increase the absorbable free water of the slag, which in turn reduces the shrinkage of the composites. It also increases the ionic concentration in the pore solution, resulting in a more complete reaction of the AASC, which can optimize the pore structure and thus improve the durability of the AASC. This study proposes a promising way to develop sustainable alkali-activated slag concrete achieved by recycling waste materials.
Awareness and intention-to-use of digital health applications, artificial intelligence and blockchain technology in breast cancer care
Authors: Griewing Sebastian , Knitza Johannes , Gremke Niklas , Wallwiener Markus , Wagner Uwe , Lingenfelder Michael , Kuhn Sebastian
Published: May 2024

Emerging digital technologies promise to improve breast cancer care, however lack of awareness among clinicians often prevents timely adoption. This study aims to investigate current awareness and intention-to-use of three technologies among breast cancer healthcare professionals (HCP): (1) digital health applications (DHA), (2) artificial intelligence (AI), and (3) blockchain technology (BC). A 22-item questionnaire was designed and administered before and after a 30 min educational presentation highlighting technology implementation examples. Technology awareness and intention-to-use were measured using 7-point Likert scales. Correlations between demographics, technology awareness, intention-to-use, and eHealth literacy (GR-eHEALS scale) were analyzed. 45 HCP completed the questionnaire, of whom 26 (57.8%) were female. Age ranged from 24 to 67 {mean age (SD): 44.93 ± 12.62}. Awareness was highest for DHA (68.9%) followed by AI (66.7%) and BC (24.4%). The presentation led to a non-significant increase of intention-to-use AI {5.37 (±1.81) to 5.83 (±1.64)}. HCPs´ intention-to-use BC after the presentation increased significantly {4.30 (±2.04) to 5.90 (±1.67), p < 0.01}. Mean accumulated score for GR-eHEALS averaged 33.04 (± 6.61). HCPs´ intended use of AI significantly correlated with eHealth literacy (ρ = 0.383; p < 0.01), intention-to-use BC (ρ = 0.591; p < 0.01) and participants´ age (ρ = −0.438; p < 0.01). This study demonstrates the effect that even a short practical presentation can have on HCPs´ intention-to-use emerging digital technologies. Training potential professional users should be addressed alongside the development of new information technologies and is crucial to increase HCPs´ corresponding awareness and intended use.
Efficacy and safety of PD-1/PD-L1 inhibitor-based immune combination therapy versus sorafenib in the treatment of advanced hepatocellular carcinoma: a meta-analysis
Authors: She Mingjin , Wu Yayun , Cheng Mengmeng , Feng Sanli , Li Guizhi , Rong Hui
Published: May 2024

Objective

To systematically evaluate the safety and efficacy of PD-1/PD-L1 inhibitor-based immunotherapy (hereafter referred to as “combination immunotherapy”) compared with that of sorafenib in the treatment of hepatocellular carcinoma (HCC).

Methods

Databases such as PubMed, Embase, and the Cochrane Library were searched from the date of their establishment to September 2023 to identify randomized controlled trials (RCTs) of combination immunotherapy versus sorafenib for the treatment of advanced HCC. Two reviewers independently evaluated the quality of the included studies, extracted the data, and cross-checked the information. The meta-analysis was performed using RevMan 5.3 software.

Results

A total of 5 RCTs were included. The results of the meta-analysis showed the following: (1) Effectiveness. Compared to sorafenib, combination immunotherapy significantly improved overall survival (OS, HR = 0.69, 95% CI: 0.58 ~ 0.82, p < 0.01) and progression-free survival (PFS, HR = 0.62, 95% CI: 0.50 ~ 0.78, p < 0.001) in patients with advanced HCC. (2) Safety. Both groups had comparatively high incidences of adverse events (AEs), but the difference in any treatment-related adverse events was not significant between the two arms (OR = 0.98, 95% CI: 0.95 ~ 1.02, p = 0.34). The difference in the incidence of grade 1–2 adverse reactions was statistically significant (OR = 0.66, 95% CI = 0.49–0.90, p = 0.001). There were no differences in grade 3/4 TRAEs or grade 5 TRAEs (OR = 1.46, 95% CI = 0.78 ~ 2.71, p = 0.24; OR = 1.08, 95% CI = 0.73 ~ 1.58, p = 0.71).

Conclusion

Combined immunotherapy can significantly prolong the OS and PFS of patients with advanced HCC without increasing the incidence of adverse effects in terms of safety, but the incidence of AEs in different systems is different.
Metagenomics profiling of the microbial community and functional differences in solid-state fermentation vinegar starter (seed Pei) from different Chinese regions
Authors: Han Dong , Yang Yunsong , Guo Zhantong , Chen Ken , Dai Shuwen , Zhu Yuanyuan , Wang Yuqin , Yu Zhen , Wang Ke , Liu Peng , Rong Chunchi , Yu Yongjian
Published: May 2024

Introduction

The starter used in solid-state fermentation (SSF) vinegar, known as seed Pei is a microbial inoculant from the previous batch that is utilized during the acetic acid fermentation stage. The seed Pei, which has a notable impact on vinegar fermentation and flavor, is under-researched with comparative studies on microorganisms.

Methods

Herein metagenomics was employed to reveal the microbes and their potential metabolic functions of four seed Pei from three regions in China.

Results

The predominant microbial taxa in all four starters were bacteria, followed by viruses, eukaryotes, and archaea, with Lactobacillus sp. or Acetobacter sp. as main functional taxa. The seed Pei used in Shanxi aged vinegar (SAV) and Sichuan bran vinegar (SBV) exhibited a higher similarity in microbial composition and distribution of functional genes, while those used in two Zhenjiang aromatic vinegar (ZAV) differed significantly. Redundancy analysis (RDA) of physicochemical factors and microbial communities indicated that moisture content, pH, and reducing sugar content are significant factors influencing microbial distribution. Moreover, seven metagenome-assembled genomes (MAGs) that could potentially represent novel species were identified.

Conclusions

There are distinctions in the microbiome and functional genes among different seed Pei. The vinegar starters were rich in genes related to carbohydrate metabolism. This research provides a new perspective on formulating vinegar fermentation starters and developing commercial fermentation agents for vinegar production.
The dispensability of VH-VL pairing and the indispensability of VL domain integrity in the IgG1 secretion process
Authors: Choi Juho , Jeon Yerin , Roh Youngin , Jang Jeongyun , Lee Eunbin , Villamante Luigie , Kim Minjae , Kwon Myung-Hee
Published: May 2024

Introduction: The CH1 domain of IgG antibodies controls assembly and secretion, mediated by the molecular chaperone BiP via the endoplasmic reticulum protein quality control (ERQC) mechanism. However, it is not clear whether the variable domains are necessary for this process.

Methods: Here, we generated IgG1 antibodies in which the V domain (VH and/or VL) was either removed or replaced, and then assessed expression, assembly, and secretion in HEK293 cells.

Results: All Ig variants formed a covalent linkage between the Cγ1 and Cκ, were successfully secreted in an assembled form. Replacement of the cognate Vκ with a non-secretory pseudo Vκ (ψVκ) hindered secretion of individual or assembled secretion of neither heavy chains (HCs) nor light chains (LCs). The ψLC (ψVκ-Cκ) exhibited a less folded structure compared to the wild type (wt) LC, as evidenced by enhanced stable binding to the molecular chaperone BiP and susceptibility to proteolytic degradation. Molecular dynamics simulation demonstrated dramatic alterations in overall structure of ψFab (Fd-ψLC) from wt Fab.

Discussion: These findings suggest that V domains do not initiate HC:LC assembly and secretion; instead, the critical factor governing IgG assembly and secretion is the CH-CL pairing. Additionally, the structural integrity of the VL domain is crucial for IgG secretion. These data offer valuable insight into the design of bioactive molecules based on an IgG backbone.
Moderating effect of education on glymphatic function and cognitive performance in mild cognitive impairment
Authors: Zhou Liang , Yang Wenxia , Liu Yang , Zheng Yu , Ge Xin , Ai Kai , Liu Guangyao , Zhang Jing
Published: May 2024

Objective

This research aims to investigate putative mechanisms between glymphatic activity and cognition in mild cognitive impairment (MCI) and analyzes whether the relationship between cognitive reserve (CR) and cognition was mediated by glymphatic activity.

Methods

54 MCI patients and 31 NCs were enrolled to evaluate the bilateral diffusivity along the perivascular spaces and to acquire an index for diffusivity along the perivascular space (ALPS-index) on diffusion tensor imaging (DTI). The year of education was used as a proxy for CR. The ALPS-index was compared between two groups and correlation analyses among the ALPS-index, cognitive function, and CR were conducted. Mediation analyses were applied to investigate the correlations among CR, glymphatic activity and cognition.

Results

MCI group had a significantly lower right ALPS-index and whole brain ALPS-index, but higher bilateral diffusivity along the y-axis in projection fiber area (Dyproj) than NCs. In MCI group, the left Dyproj was negatively related to cognitive test scores and CR, the whole brain ALPS-index was positively correlated with cognitive test scores and CR. Mediation analysis demonstrated that glymphatic activity partially mediated the correlations between CR and cognitive function.

Conclusion

MCI exhibited decreased glymphatic activity compared to NCs. CR has a protective effect against cognitive decline in MCI, and this effect may be partially mediated by changes in glymphatic activity.
Three major effects of APOEε4 on Aβ immunotherapy induced ARIA
Authors: Foley Kate E. , Wilcock Donna M.
Published: May 2024

The targeting of amyloid-beta (Aβ) plaques therapeutically as one of the primary causes of Alzheimer’s disease (AD) dementia has been an ongoing effort spanning decades. While some antibodies are extremely promising and have been moved out of clinical trials and into the clinic, most of these treatments show similar adverse effects in the form of cerebrovascular damage known as amyloid-related imaging abnormalities (ARIA). The two categories of ARIA are of major concern for patients, families, and prescribing physicians, with ARIA-E presenting as cerebral edema, and ARIA-H as cerebral hemorrhages (micro- and macro-). From preclinical and clinical trials, it has been observed that the greatest genetic risk factor for AD, APOEε4, is also a major risk factor for anti-Aβ immunotherapy-induced ARIA. APOEε4 carriers represent a large population of AD patients, and, therefore, limits the broad adoption of these therapies across the AD population. In this review we detail three hypothesized mechanisms by which APOEε4 influences ARIA risk: (1) reduced cerebrovascular integrity, (2) increased neuroinflammation and immune dysregulation, and (3) elevated levels of CAA. The effects of APOEε4 on ARIA risk is clear, however, the underlying mechanisms require more research.
Iridoids rich fraction from Valeriana jatamansi Jones promotes axonal regeneration and motor functional recovery after spinal cord injury through activation of the PI3K/Akt signaling pathway
Authors: Wang Yunyun , Lu Jiachun , Xiao Hua , Ding Lijuan , He Yongzhi , Chang Cong , Wang Wenchun
Published: May 2024

Valeriana jatamansi Jones (VJJ), renowned for its extensive history in traditional Chinese medicine and ethnomedicine within China, is prevalently utilized to alleviate ailments such as epigastric distension and pain, gastrointestinal disturbances including food accumulation, diarrhea, and dysentery, as well as insomnia and other diseases. Moreover, the Iridoid-rich fraction derived from Valeriana jatamansi Jones (IRFV) has demonstrated efficacy in facilitating the recuperation of motor functions after spinal cord injury (SCI). This study is aimed to investigate the therapeutic effect of IRFV on SCI and its underlying mechanism. Initially, a rat model of SCI was developed to assess the impact of IRFV on axonal regeneration. Subsequently, employing the PC12 cell model of oxidative damage, the role and mechanism of IRFV in enhancing axonal regeneration were explored using the phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway inhibitor LY294002. Ultimately, the same inhibitor was administered to SCI rats to confirm the molecular mechanism through which IRFV promotes axonal regeneration by activating the PI3K/Akt signaling pathway. The results showed that IRFV significantly enhanced motor function recovery, reduced pathological injury, and facilitated axonal regeneration in SCI rats. In vitro experiments revealed that IRFV improved PC12 cell viability, augmented axonal regeneration, and activated the PI3K/Akt signaling pathway. Notably, the inhibition of this pathway negated the therapeutic benefits of IRFV in SCI rats. In conclusion, IRFV promote promotes axonal regeneration and recovery of motor function after SCI through activation of the PI3K/Akt signaling pathway.
The role of green tea intake in thromboprophylaxis of venous thromboembolism in patients with cancer
Authors: Yao Qihuan , Qiao Hongwei , Cheng Yi , Du He , Zhang Yanbin , Luo Yong , Wang Hongwei , Liu Song , Xu Mei , Xiong Wei
Published: May 2024

Background

Green tea intake has been reported to improve the clinical outcomes of patients with cardiovascular diseases or cancer. It may have a certain role in the development of venous thromboembolism (VTE) among cancer patients. The current study aimed to address this issue, which has been understudied.

Methods

We carried out a retrospective study to explore the role of green tea intake in cancer patients. Patients with and without green tea intake were enrolled in a 1:1 ratio by using propensity scoring matching. The primary and secondary outcomes were VTE development and mortality 1 year after cancer diagnosis, respectively.

Results

The cancer patients with green tea intake (n = 425) had less VTE development (10 [2.4%] vs. 23 [5.4%], p = 0.021), VTE-related death (7 [1.6%] vs. 18 [4.2%], p = 0.026), and fatal pulmonary embolism (PE) (3 [0.7%] vs. 12 [2.8%], p = 0.019), compared with those without green tea intake (n = 425). No intake of green tea was correlated with an increase in VTE development (multivariate hazard ratio (HR) 1.758 [1.476–2.040], p < 0.001) and VTE-related mortality (HR 1.618 [1.242–1.994], p = 0.001), compared with green tea intake. Patients with green tea intake less than 525 mL per day had increased VTE development (area under the curve (AUC) 0.888 [0.829–0.947], p < 0.001; HR1.737 [1.286–2.188], p = 0.001) and VTE-related mortality (AUC 0.887 [0.819–0.954], p < 0.001; HR 1.561 [1.232–1.890], p = 0.016) than those with green tea intake more than 525 mL per day. Green tea intake caused a decrease in platelet (p < 0.001) instead of D-dimer (p = 0.297). The all-cause mortality rates were similar between green tea (39 [9.2%]) and non-green tea (48 [11.3%]) intake groups (p = 0.308), whereas the VTE-related mortality rate in the green tea intake group (7 [1.6%]) was lower than that of the non-green tea intake group (18 [4.2%]) (p = 0.026). The incidences of adverse events were similar between the green tea and non-green tea intake groups.

Conclusion

In conclusion, the current study suggests that green tea intake reduces VTE development and VTE-related mortality in cancer patients, most likely through antiplatelet mechanisms. Drinking green tea provides the efficacy of thromboprophylaxis for cancer patients.
Pycnogenol® French maritime pine bark extract in randomized, double-blind, placebo-controlled human clinical studies
Authors: Weichmann Franziska , Rohdewald Peter
Published: May 2024

Pycnogenol® French maritime pine bark extract is a well-known and thoroughly studied patented extract from the bark of Pinus pinaster Ait. ssp. Atlantica. In 39 randomized double-blind, placebo-controlled (RDP) human clinical trials including 2,009 subjects, Pycnogenol® French maritime pine bark extract supplementation for two weeks to six months has been shown to beneficially affect cardiovascular health, chronic venous insufficiency, cognition, joint health, skin health, eye health, women’s health, respiratory health and allergies, oral health and sports performance. The mechanisms of action that can explain the respective effects on different conditions in the human body are discussed as well. As investigated in several in vitro, in vivo and in clinical studies, Pycnogenol® French maritime pine bark extract showed antioxidative effects, anti-inflammatory abilities, beneficial effects on endothelial function and reinforcing effects on the extracellular matrix. The present review aims to give a comprehensive overview of currently available “gold standard” RDP trials of Pycnogenol®’s benefits across various health domains compared to placebo. In addition, some of the processes on which the presented effects of Pycnogenol® French maritime pine bark extract are based will be elucidated and discussed. This broad overview of RDP studies on Pycnogenol® in different health domains can be used as a basis for further research on applications and mechanisms of this unique French maritime pine bark extract.
Clinical outcomes for olfactory neuroblastoma
Authors: Nakazono Akira , Motegi Hiroaki , Suzuki Masanobu , Nakamaru Yuji , Yamaguchi Shigeru , Ishi Yukitomo , Kano Satoshi , Tsushima Nayuta , Honma Aya , Suzuki Takayoshi , Kimura Shogo , Hamada Seijiro , Taguchi Jun , Shimizu Yasushi , Mori Takashi , Yasuda Koichi , Aoyama Hidefumi , Kinoshita Ichiro , Fujimura Miki , Homma Akihiro
Published: May 2024

Background

Olfactory neuroblastoma (ONB) is a rare malignant tumor arising from the olfactory neuroepithelium. The standard of care for ONB is surgical resection; however, detailed treatment protocols vary by institution. Our treatment protocol consists of endoscopic skull base surgery (ESBS) for endoscopically resectable cases and induction chemotherapy followed by craniotomy combined with ESBS for locally advanced cases, with postoperative radiotherapy performed for all cases. Chemoradiotherapy (CRT) is performed in unresectable cases. In this study, we evaluate our treatment protocol and outcomes for ONB.

Methods

A retrospective review of patients with ONB was conducted. Outcomes included survival outcomes and perioperative data.

Results

Fifteen patients (53.6%) underwent ESBS, 12 (42.9%) underwent craniotomy combined with ESBS, and 1 (3.6%) received CRT. The 5- and 10-year overall survival rates for all patients were 92.9% and 82.5%, respectively, with a median follow-up period of 81 months. The 5- and 10-year disease-free survival rates were 77.3% and 70.3%, respectively, and the 5- and 10-year local control rates were 88.2% and 80.2%, respectively. Patients undergoing ESBS demonstrated a significantly shorter operating time, period from operation to ambulation, hospitalization period, and less blood loss than those undergoing craniotomy combined with ESBS.

Conclusion

Our treatment protocol was found to afford favorable outcomes. Patients who underwent endoscopic resection showed lower complication rates and better perioperative data than those who underwent craniotomy combined with ESBS. With appropriate case selection, ESBS is considered a useful approach for ONB.
Spontaneous remission of choroidal involvement by chronic myelomonocytic leukemia: a case report
Authors: Diral Elisa , Catalano Gloria , Cicinelli Maria Vittoria , Distefano Andrea , Mastaglio Sara , Vago Luca , Lupo Stanghellini Maria Teresa , Bernardi Massimo , Ponzoni Maurilio , Ciceri Fabio , Carrabba Matteo G.
Published: May 2024

Chronic myelomonocytic leukemia (CMML) is a rare hematological disorder characterized by variable risk of evolution to acute myeloid leukemia; to date, allogeneic stem cell transplantation is the only curative treatment. We report a case of choroidal involvement in a woman affected by CMML and presenting only with visual impairment. The patient was initially evaluated for an intensive therapeutic approach, but after biopsy the ocular lesion spontaneously regressed. Thus a “watch and wait” strategy was preferred. One year and a half after initial diagnosis, the patient is alive, with stable hematological disease and without any ocular involvement. Therefore, a close, not invasive follow up could be useful to tailor treatment for patients affected by single ocular lesions in CMML.
Case Report: Virtual natural environment solution helped a child cope with a painful procedure
Authors: Karppa Elina , Puura Kaija , Jyskä Ilmari , Turunen Markku , Palmu Sauli
Published: May 2024

Fear of needles is a common phenomenon that can affect the patient's ability to function and to seek medical help. Novel treatment practices are needed to help children cope with this fear. Based on user feedback, immersive virtual reality applications are effective when distracting the patient during a painful procedure. Better understanding of how virtual reality solutions affect the autonomic nervous system should be acquired. We present the case of a 12-year-old boy attending our study examining a novel virtual reality (VR) relaxation method (VirNE). The clinical study aims to determine if pain and anxiety can be relieved by relaxation that has been induced by a virtual natural environment and guided relaxation exercise-mediated autonomic nervous system stimulation. The patient was able to overcome his fear of needles with the help of the guided relaxation and found significant relief from the distress he was experiencing on his monthly visits to the hospital due to his long-term illness requiring repetitious intravenous cannulations.
Exosomes derived from HUVECs alleviate ischemia-reperfusion induced inflammation in neural cells by upregulating KLF14 expression
Authors: Qin Jianxin , Zhou Lihong , Yu Lei , Ye Jingwen , Wang Feng , Zhou Jin , Gu Yunjuan , Chen Gang , Chen Xia
Published: May 2024

Neuroinflammation plays a key role in the progression of secondary brain injury after ischemic stroke, and exosomes have been increasingly recognized to eliminate inflammatory responses through various mechanisms. This study aimed to explore the effect and possible mechanism of human umbilical vein endothelial cells derived exosomes (H-EXOs) on neuroinflammation. We established a transient middle cerebral artery occlusion/reperfusion (tMCAO/R) in male rats and oxygen-glucose-deprivation/reoxygenation (OGD/R) model in cultured neurons to mimic secondary brain injury after ischemic stroke in vivo. H-EXOs were administered at the same time of reperfusion. Results showed that the production of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, and the transcription factor Krüppel-like factor 14 (KLF14) were significantly increased both in rat brain tissue and cultured neural cells after ischemic-reperfusion (I/R) injury. H-EXOs treatment significantly improved the cultured cell viability, reduced infarct sizes, mitigated neurobehavioral defects, and alleviated the expression of pro-inflammatory cytokines compared with the control group, indicating that H-EXOs exerted anti-inflammatory effect against I/R injury. Further studies revealed that the anti-inflammatory effect of H-EXOs could be weakened by small-interfering RNA (siKLF4) transfection. KLF14 was a protective factor produced during cerebral ischemia-reperfusion injury. In conclusion, H-EXOs protect neurons from inflammation after I/R injury by enhancing KLF14 expression.
The road to evolution of ProTx2: how to be a subtype-specific inhibition of human Nav1.7
Authors: Zhao Fan , Liu Yuanyuan , Liu Yiyu , Ye Qi , Yang Hongtao , Gui Mingze , Song Yongbo
Published: May 2024

The human voltage-gated sodium channel Nav1.7 is a widely proven target for analgesic drug studies. ProTx2, a 30-residue polypeptide from Peruvian green tarantula venom, shows high specificity to activity against human Nav1.7, suggesting its potential to become a non-addictive analgesic. However, its high sensitivity to human Nav1.4 raises concerns about muscle side effects. Here, we engineered three mutants (R13A, R13D, and K27Y) of ProTx2 to evaluate their pharmacological activities toward Nav1.7 and Nav1.4. It is demonstrated that the mutant R13D maintained the analgesic effect in mice while dramatically reducing its muscle toxicity compared with ProTx2. The main reason is the formation of a strong electrostatic interaction between R13D and the negatively charged amino acid residues in DII/S3-S4 of Nav1.7, which is absent in Nav1.4. This study advances our understanding and insights on peptide toxins, paving the way for safer, effective non-addictive analgesic development.
Discovering new genes for alfalfa (Medicago sativa) growth and biomass resilience in combined salinity and Phoma medicaginis infection through GWAS
Authors: Mnafgui Wiem , Jabri Cheima , Jihnaoui Nada , Maiza Nourhene , Guerchi Amal , Zaidi Nawres , Basson Gerhard , Keyster Eden Maré , Djébali Naceur , Pecetti Luciano , Hanana Mohsen , Annicchiarico Paolo , Sakiroglu Muhammet , Ludidi Ndiko , Badri Mounawer
Published: May 2024

Salinity and Phoma medicaginis infection represent significant challenges for alfalfa cultivation in South Africa, Europe, Australia, and, particularly, Tunisia. These constraints have a severe impact on both yield and quality. The primary aim of this study was to establish the genetic basis of traits associated with biomass and growth of 129 Medicago sativa genotypes through genome-wide association studies (GWAS) under combined salt and P. medicaginis infection stresses. The results of the analysis of variance (ANOVA) indicated that the variation in these traits could be primarily attributed to genotype effects. Among the test genotypes, the length of the main stem, the number of ramifications, the number of chlorotic leaves, and the aerial fresh weight exhibited the most significant variation. The broad-sense heritability (H²) was relatively high for most of the assessed traits, primarily due to genetic factors. Cluster analysis, applied to morpho-physiological traits under the combined stresses, revealed three major groups of accessions. Subsequently, a GWAS analysis was conducted to validate significant associations between 54,866 SNP-filtered single-nucleotide polymorphisms (SNPs) and seven traits. The study identified 27 SNPs that were significantly associated with the following traits: number of healthy leaves (two SNPs), number of chlorotic leaves (five SNPs), number of infected necrotic leaves (three SNPs), aerial fresh weight (six SNPs), aerial dry weight (nine SNPs), number of ramifications (one SNP), and length of the main stem (one SNP). Some of these markers are related to the ionic transporters, cell membrane rigidity (related to salinity tolerance), and the NBS_LRR gene family (associated with disease resistance). These findings underscore the potential for selecting alfalfa genotypes with tolerance to the combined constraints of salinity and P. medicaginis infection.
The roles of intrinsic motivation and capability-related factors in cognitive effort-based decision-making
Authors: Randez Alyssa , Hélie Sébastien
Published: May 2024

Individual differences in cognitive effort-based decision-making can be used to reveal human motivations to invest effort into a given task. Preferences among options that differ by dimensions related to demand levels (i.e., the interaction of task characteristics and performance measures) are also heavily influenced by how likely a person can succeed at a given option. However, most existing cognitive effort-based research has focused primarily on demand-related factors, leading to confounding inferences about the motivation behind these choices. This study used an adaptive algorithm to adjust relative demand levels for three cognitive tasks to investigate general and individual differences in demand preferences. The results highlight an overall pattern of individual differences in intrinsic motivation to perform challenging tasks, supporting research that found cognitive effort aversive to some but attractive to others. These results suggest that relative demand levels and intrinsic task factors drive the motivation to select an action.
Association between plasma long-chain polyunsaturated n-3 fatty acids concentrations and cognitive function: findings from NHANES III
Authors: Li Xiaojing , Huang Zijie , Tian Yueqin , Chen Xing , Wu Haidong , Wang Tong
Published: May 2024

Background

With increased life expectancy, cognitive decline has emerged as a prevalent neurodegenerative disorder.

Objective

This study aimed to examine the correlation between concentrations of Plasma long-chain n-3 polyunsaturated fatty acids (LCPUFAs) and cognitive performance in elderly Americans.

Methods

Data were analyzed from older adults enrolled in two NHANES cycles. Participants completed four cognitive assessments, including the Immediate Recall Test (IRT), Delayed Recall Test (DRT), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). Linear regression and restricted cubic spline modeling examined associations between plasma LCPUFAs levels and cognitive test outcomes.

Results

The cohort included 610 adults aged 69 years on average, 300 (49.2%) males and 310 (50.8%) females. The median LCPUFAs concentration was 309.4 μmol/L, with an interquartile range of 244.7–418.9 μmol/L. In unadjusted and adjusted generalized linear regression model analyses, circulating LCPUFAs exhibited significant positive correlations with DRT performance. No relationships were detected among those with chronic conditions (chronic heart failure, stroke, diabetes). A significant association between LCPUFAs levels and DRT scores was evident in males but not females.

Conclusion

Plasma LCPUFAs concentrations were significantly associated with DRT performance in males free of chronic illnesses, including heart failure, stroke, and diabetes.
The role of the target language culture on Arabic learners' fondness for Arabic poetry
Authors: Gao Li , Wang Kai , Yang Qian , Lu Yiwei
Published: May 2024

As an important carrier of culture, poetry plays a significant role in deepening language learners' understanding of the target language culture as well as enhancing their language skills; however, the effect of the target language culture on language learners' enjoyment of poetry remains unclear. The study served as an attempt to shed light on the point of whether the target language culture has different effects on high- and low-level Chinese Arabic learners' fondness for Arabic poetry with the use of pictures related to Arabic culture and those not related to Arabic culture. In the current study, 40 Arabic learners (20 high-level and 20 low-level) scored the Arabic poem line based on their fondness for it after viewing two kinds of picture with electroencephalogram (EEG) recording. Frontal alpha asymmetry index as a correlate of approach and avoidance related motivation measured by EEG power in the alpha band (8-13 Hz) was calculated for examining whether the behavioral results of Arabic learners' fondness for poetry are in line with the results of changes in the related EEG components. Behavioral results illustrated that low-level subjects showed significantly less liking for Arabic poetry after viewing pictures related to Arabic culture compared to those not related to Arabic culture. The high-level subjects did not show a significant difference in the level of liking for Arabic poetry between the two cases. FAA results demonstrated that low-level subjects presented a significant avoidance-related responses to Arabic poetry after viewing pictures related to Arabic culture in comparison to viewing pictures not related to Arabic culture; while the FAA values did not differ significantly between the two cases in high-level subjects, which is in line with behavioral results. The findings of this research can benefit teachers in motivating students to learn poetry in foreign language curriculum and also contribute to the literature on the effect of target language culture on language learners' enjoyment of poetry.
Trauma-sensitive school concepts for students with a refugee background: a review of international studies
Authors: Lembke Eva J. , Linderkamp Friedrich , Casale Gino
Published: May 2024

Children and adolescents with a refugee background are at high risk for traumatization. Once they arrive in safe countries, schools are the institutions where teachers are responsible for caring for them sensitively and competently. Furthermore, schools are organized in learning groups consisting of multiple peers of the same age, which provides excellent opportunities for social learning and experiences of social support. In this respect, schools are the appropriate places where preventive concepts can be applied to students with a refugee background. This systematic review summarizes studies that examine or evaluate existing international concepts of trauma-sensitive schools for supporting traumatized students with a refugee background. Based on N = 41 selected articles, 17 relevant concepts of trauma-sensitive schools were identified. In 35.3% of the concepts, traumatized students with a refugee background are explicitly included in the target group of the concept, while 47.1% of the concepts refer to groups of students with trauma as a result of various adverse childhood experiences, which also occur more frequently within the population of refugee children and adolescents 17.6% of the concepts contain specific adaptations for pupils with a refugee background. The majority of these concepts were developed in the United States. Additional concepts can be reported for Australia, the United Kingdom, Turkey, and Cambodia. Based on available empirical data, no significant effectiveness regarding the researched concepts’ effects on academic and other school-related data can be determined. Although some studies indicate positive effects concerning school-related target variables, most of the studies have only limited significance due to inadequate research designs and methodological deficiencies. Therefore, there is a great need for further development, careful implementation, and evaluation of trauma-sensitive concepts in schools, especially for the growing group of refugee students.
The effect of cognitive load, ego depletion, induction and time restriction on moral judgments about sacrificial dilemmas: a meta-analysis
Authors: Rehren Paul
Published: May 2024

Greene's influential dual-process model of moral cognition (mDPM) proposes that when people engage in Type 2 processing, they tend to make consequentialist moral judgments. One important source of empirical support for this claim comes from studies that ask participants to make moral judgments while experimentally manipulating Type 2 processing. This paper presents a meta-analysis of the published psychological literature on the effect of four standard cognitive-processing manipulations (cognitive load; ego depletion; induction; time restriction) on moral judgments about sacrificial moral dilemmas [n = 44; k = 68; total N = 14, 003; M(N) = 194.5]. The overall pooled effect was in the direction predicted by the mDPM, but did not reach statistical significance. Restricting the dataset to effect sizes from (high-conflict) personal sacrificial dilemmas (a type of sacrificial dilemma that is often argued to be best suited for tests of the mDPM) also did not yield a significant pooled effect. The same was true for a meta-analysis of the subset of studies that allowed for analysis using the process dissociation approach [n = 8; k = 12; total N = 2, 577; M(N) = 214.8]. I argue that these results undermine one important line of evidence for the mDPM and discuss a series of potential objections against this conclusion.