bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated levels of cell-free NKG2D-ligands modulate NKG2D surface expression and compromise NK cell function in severe COVID-19 disease
Authors: Fernández-Soto Daniel , García-Jiménez Álvaro F. , Casasnovas José M. , Valés-Gómez Mar , Reyburn Hugh T.
Published: February 2024

Introduction

It is now clear that coronavirus disease 19 (COVID-19) severity is associated with a dysregulated immune response, but the relative contributions of different immune cells is still not fully understood. SARS CoV-2 infection triggers marked changes in NK cell populations, but there are contradictory reports as to whether these effector lymphocytes play a protective or pathogenic role in immunity to SARS-CoV-2.

Methods

To address this question we have analysed differences in the phenotype and function of NK cells in SARS-CoV-2 infected individuals who developed either very mild, or life-threatening COVID-19 disease.

Results

Although NK cells from patients with severe disease appeared more activated and the frequency of adaptive NK cells was increased, they were less potent mediators of ADCC than NK cells from patients with mild disease. Further analysis of peripheral blood NK cells in these patients revealed that a population of NK cells that had lost expression of the activating receptor NKG2D were a feature of patients with severe disease and this correlated with elevated levels of cell free NKG2D ligands, especially ULBP2 and ULBP3 in the plasma of critically ill patients. In vitro, culture in NKG2DL containing patient sera reduced the ADCC function of healthy donor NK cells and this could be blocked by NKG2DL-specific antibodies.

Discussion

These observations of reduced NK function in severe disease are consistent with the hypothesis that defects in immune surveillance by NK cells permit higher levels of viral replication, rather than that aberrant NK cell function contributes to immune system dysregulation and immunopathogenicity.
Exploring the interplay between posttraumatic stress disorder, gut microbiota, and inflammatory biomarkers: a comprehensive meta-analysis
Authors: Petakh Pavlo , Oksenych Valentyn , Kamyshna Iryna , Boisak Iryna , Lyubomirskaya Katerina , Kamyshnyi Oleksandr
Published: February 2024

Introduction

Posttraumatic stress disorder (PTSD) is the most common mental health disorder to develop following exposure to trauma. Studies have reported conflicting results regarding changes in immune biomarkers and alterations in the abundance of bacterial taxa and microbial diversity in patients with PTSD.

Aim

The purpose of this meta-analysis is to summarize existing studies examining gut microbiota characteristics and changes in immune biomarkers in patients with PTSD.

Methods

Relevant studies were systematically searched in PubMed, Scopus, and Embase, published in English between January 1, 1960, and December 1, 2023. The outcomes included changes in abundance and diversity in gut microbiota (gut microbiota part) and changes in immune biomarkers (immune part).

Results

The meta-analysis included a total of 15 studies, with 9 focusing on changes in inflammatory biomarkers and 6 focusing on changes in gut microbiota composition in patients with PTSD. No differences were observed between groups for all inflammatory biomarkers (P≥0.05). Two of the six studies found that people with PTSD had less alpha diversity. However, the overall Standardized Mean Difference (SMD) for the Shannon Diversity Index was not significant (SMD 0.27, 95% CI -0.62–0.609, p = 0.110). Regarding changes in abundance, in two of the studies, a significant decrease in Lachnospiraceae bacteria was observed.

Conclusion

This meta-analysis provides a comprehensive overview of gut microbiota characteristics in PTSD, suggesting potential associations with immune dysregulation. Future research should address study limitations, explore causal relationships, and consider additional factors influencing immune function in individuals with PTSD.

Systematic review registration

https://www.crd.york.ac.uk, identifier CRD42023476590.
Enhancing ENSO predictions with self-attention ConvLSTM and temporal embeddings
Authors: Rui Chuang , Sun Zhengya , Zhang Wensheng , Liu An-An , Wei Zhiqiang
Published: February 2024

El Niño-Southern Oscillation (ENSO), a cyclic climate phenomenon spanning interannual and decadal timescales, exerts substantial impacts on the global weather patterns and ecosystems. Recently, deep learning has brought considerable advances in the accurate prediction of ENSO occurrence. However, the current models are insufficient to characterize the evolutionary behavior of the ENSO, particularly lacking comprehensive modeling of local-range and longrange spatiotemporal interdependencies, and the incorporation of calendar monthly and seasonal properties. To make up this gap, we propose a Two-Stage SpatioTemporal (TSST) autoregressive model that couples the meteorological factor prediction with ENSO indicator prediction. The first stage predicts the meteorological time series by leveraging self-attention ConvLSTM network which captures both the local and the global spatial-temporal dependencies. The temporal embeddings of calendar months and seasonal information are further incorporated to preserves repeatedly-occurring-yet-hidden patterns in meteorological series. The second stage uses multiple layers to extract higher level of features from predicted meteorological factors progressively to generate ENSO indicators. The results demonstrate that our model outperforms the state-of-the-art ENSO prediction models, effectively predicting ENSO up to 24 months and mitigating the spring predictability barrier.
Modeling carbon dioxide removal via sinking of particulate organic carbon from macroalgae cultivation
Authors: Chen Si , Strong-Wright Jago , Taylor John R.
Published: February 2024

Macroalgae cultivation is receiving growing attention as a potential carbon dioxide removal (CDR) strategy. Macroalgae biomass harvesting and/or intentional sinking have been the main focus of research efforts. A significant amount of biomass is naturally lost through erosion and breakage of cultivated or naturally growing seaweed, but the contribution of the resulting particulates to carbon sequestration is relatively unexplored. Here, we use a fully coupled kelp-biogeochemistry model forced by idealized parameters in a closed system to estimate the potential of macroalgal-derived particulate organic carbon (POC) sinking as a CDR pathway. Our model indicates that at a kelp density of 1.1 fronds m−3, macroalgal POC sinking can export 7.4 times more carbon to the deep sea (depths > 500m) and remove 5.2 times more carbon from the atmosphere (equivalent to an additional 336.0 gC m−2 yr−1) compared to the natural biological pump without kelp in our idealized closed system. The results suggest that CDR associated with POC sinking should be explored as a possible benefit of seaweed farming and point to the need for further study on organic carbon partitioning and its bioavailability to quantify the effectiveness and impacts of macroalgal cultivation as a CDR strategy.
Effectiveness of a multicomponent exercise intervention in community-dwelling older Chinese people with cognitive frailty: protocol for a mixed-methods research
Authors: Ning Hongting , Chen Fenghui , Li Junxin , Du Yan , Chen Xi , Wu Shuang , Joseph Abigael , Gao Yinyan , Cao Zeng , Feng Hui
Published: February 2024

Aims

To evaluate the effectiveness of a multicomponent exercise intervention and to clarify the underlying mechanisms of the program in community-dwelling older adults with cognitive frailty. Additionally, the perception of participants in the program will be explored.

Design

A mixed-methods design, including a randomized controlled trial and an exploratory qualitative study, was used.

Methods

Each group consists of 41 participants. The experimental group will undergo a 12-week multicomponent exercise intervention, including warm-up, exergaming aerobic exercise, elastic-band resistance exercise, and cool-down. This intervention was developed based on the Health Belief Model (HBM) and Self-Efficacy Model (SEM). The control group will not receive any intervention. Physical frailty and cognitive function will be considered as primary outcomes. Data will be collected both at baseline and at the end of the intervention period. Fisher’s exact test, analysis of covariance, and generalized linear models will be conducted to compare mean changes between the two groups. Additionally, the mediation models will be used to examine whether any intervention effects are mediated through exercise self-efficacy.

Discussion

The findings of this study are anticipated to provide valuable insights for healthcare providers, enabling them to learn about effective strategies to enhance exercise adherence and promote improved functionality, independence, and quality of life for older adults with cognitive frailty.

Clinical trial registration: [https://clinicaltrials.gov/], identifier [ChiCTR2200058850].
Cerebellar encephalitis associated with anti-mGluR1 antibodies: a case report and comprehensive literature review
Authors: Chen Xue , Chen Yanan , Di Lu , Liu Na , Liu Ting , Cai Yun , Di Weiying
Published: February 2024

Anti-metabotropic glutamate receptor 1 encephalitis is an uncommon autoimmune condition characterized by a subacute onset of cerebellar syndrome. Frequently, it also manifests as sleep disorders and cognitive or behavioral changes. While immunotherapy is the primary treatment approach, the disease remains poorly understood. Herein, we present a case of anti-metabotropic glutamate receptor 1 encephalitis, highlighting its primary cerebellar syndrome manifestation. The first magnetic resonance imaging scan showed no obvious abnormality. Lumbar puncture showed increased cerebrospinal fluid pressure, increased white blood cell count and protein level. The next-generation sequencing of cerebrospinal fluid showed Epstein–Barr virus infection, and the patient was diagnosed with viral cerebellar encephalitis. However, antiviral therapy was ineffective. Finally, anti-metabotropic glutamate receptor 1 was measured at 1:1,000, and the patient was definitely diagnosed with anti-metabotropic glutamate receptor 1 encephalitis. Therefore, clinicians should pay attention to such diseases to avoid misdiagnosis.
Effects of rhythmic visual cues on cortical activation and functional connectivity features during stepping: an fNIRS study
Authors: Wu Jiajia , Zhou Huilin , Chen Hao , Jiang Wensong , Wang Xuelian , Meng Tao , Wu Chaowen , Li Li , Wu Yuemin , Fan Weinv , Shi Changcheng , Zuo Guokun
Published: February 2024

Introduction

Rhythmic visual cues (RVCs) may influence gait initiation by modulating cognition resources. However, it is unknown how RVCs modulate cognitive resources allocation during gait movements. This study focused on investigating the effects of RVCs on cortical hemodynamic response features during stepping to evaluate the changes of cognitive resources.

Methods

We recorded cerebral hemoglobin concentration changes of 14 channels in 17 healthy subjects using functional near-infrared spectroscopy (fNIRS) during stepping tasks under exposure to RVCs and non-rhythmic visual cues (NRVCs). We reported mean oxygenated hemoglobin (HbO) concentration changes, β-values, and functional connectivity (FC) between channels.

Results

The results showed that, the RVC conditions revealed lower HbO responses compared to the NRVC conditions during the preparation and early stepping. Correspondingly, the β-values reflected that RVCs elicited lower hemodynamic responses than NRVCs, and there was a decreasing trend in stimulus-evoked cortical activation as the task progressed. However, the FC between channels were stronger under RVCs than under NRVCs during the stepping progress, and there were more significant differences in FC during the early stepping.

Discussion

In conclusion, there were lower cognitive demand and stronger FC under RVC conditions than NRVC conditions, which indicated higher efficiency of cognitive resources allocation during stepping tasks. This study may provide a new insight for further understanding the mechanism on how RVCs alleviate freezing of gait.
Transcriptomic analysis reveals prolonged neurodegeneration in the hippocampus of adult C57BL/6N mouse deafened by noise
Authors: Lee Sang-Youp , Lee Ho Sun , Park Min-Hyun
Published: February 2024

Introduction

Several studies have reported a significant correlation between noise-induced hearing loss and cognitive decline. However, comprehensive analyses of this relationship are rare. This study aimed to assess the influence of hearing impairment on cognitive functions by analyzing organ samples in the afferent auditory pathway of deafened mice using mRNA sequencing.

Methods

We prepared 10 female 12-week-old C57BL/6N mice as the experimental and control groups in equal numbers. Mice in the experimental group were deafened with 120 dB sound pressure level (SPL) wideband noise for 2 h. Cochlea, auditory cortex, and hippocampus were obtained from all mice. After constructing cDNA libraries for the extracted RNA from the samples, we performed next-generation sequencing. Subsequently, we analyzed the results using gene ontologies (GOs) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway databases for differentially expressed genes (DEGs) of each organ.

Results

Our results revealed 102, 89, and 176 DEGs for cochlea, auditory cortex, and hippocampus, respectively. We identified 294, 203, and 211 GOs; 10, 7, and 17 KEGG pathways in the cochlea, auditory cortex, and hippocampus, respectively. In the long term (12 weeks) from noise-induced hearing loss, GOs and KEGG pathways related to apoptosis or inflammation persisted more actively in the order of hippocampus, auditory cortex, and cochlea.

Discussion

This implies that the neurodegenerative effects of noise exposure persist more longer time in the central regions.
Expression of red/green-cone opsin mutants K82E, P187S, M273K result in unique pathobiological perturbations to cone structure and function
Authors: Sechrest Emily R. , Barbera Robert J. , Ma Xiaojie , Dyka Frank , Ahn Junyeop , Brothers Brooke A. , Cahill Marion E. , Hall Isaac , Baehr Wolfgang , Deng Wen-Tao
Published: February 2024

Long-and middle-wavelength cone photoreceptors, which are responsible for our visual acuity and color vision, comprise ~95% of our total cone population and are concentrated in the fovea of our retina. Previously, we characterized the disease mechanisms of the L/M-cone opsin missense mutations N94K, W177R, P307L, R330Q and G338E, all of which are associated with congenital blue cone monochromacy (BCM) or color-vision deficiency. Here, we used a similar viral vector-based gene delivery approach in M-opsin knockout mice to investigate the pathogenic consequences of the BCM or color-vision deficient associated L-cone opsin (OPN1LW) mutants K82E, P187S, and M273K. We investigated their subcellular localization, the pathogenic effects on cone structure, function, and cone viability. K82E mutants were detected predominately in cone outer segments, and its expression partially restored expression and correct localization of cone PDE6α’ and cone transducin γ. As a result, K82E also demonstrated the ability to mediate cone light responses. In contrast, expression of P187S was minimally detected by either western blot or by immunohistochemistry, probably due to efficient degradation of the mutant protein. M273K cone opsin appeared to be misfolded as it was primarily localized to the cone inner segment and endoplasmic reticulum. Additionally, M273K did not restore the expression of cone PDE6α’ and cone transducin γ in dorsal cone OS, presumably by its inability to bind 11-cis retinal. Consistent with the observed expression pattern, P187S and M273K cone opsin mutants were unable to mediate light responses. Moreover, expression of K82E, P187S, and M273K mutants reduced cone viability. Due to the distinct expression patterns and phenotypic differences of these mutants observed in vivo, we suggest that the pathobiological mechanisms of these mutants are distinct.
Does millet consumption contribute to raising blood hemoglobin levels compared to regular refined staples?: a systematic review and meta-analysis
Authors: Anitha Seetha , Tsusaka Takuji W. , Givens D. Ian , Kane-Potaka Joanna , Botha Rosemary , Sulaiman Nur Liana Binti , Upadhyay Shweta , Vetriventhan Mani , Rajendran Ananthan , Parasannanavar Devraj J. , Longvah Thingnganing , Subramaniam Kowsalya , Bhandari Raj Kumar
Published: February 2024

Millets are recognized for their health and nutritional values, and the United Nations declared 2023 the International Year of Millets. Among the several health and nutritional benefits of millets, their impact on hemoglobin concentration is important since anemia is a major public health issue in many countries. To investigate the effect of millet (including sorghum) consumption on hemoglobin concentration in the blood, a systematic review and meta-analysis were conducted. Thirteen published studies featuring randomized control trials involving 590 individuals in the intervention group and 549 control individuals were eligible for the meta-analysis. The difference-in-differences analysis revealed highly significant (p < 0.01) positive effects of millet consumption on hemoglobin concentration, with an effect size of +0.68 standardized mean difference units. The change in hemoglobin concentration observed in the intervention group was +13.6%, which is statistically significant (p < 0.0005), compared to that in the control group, which was +4.8% and not statistically significant (p = 0.1362). In four studies, the consumption of millets in the intervention group demonstrated a change from mild anemia to normal status among children, whereas there was no change in the control group. The findings provide evidence that the consumption of millets can improve blood hemoglobin concentration, likely resulting from increased iron intake. Further research is needed involving the assessment of iron content and bioavailability to better understand the effect variation among millet types and the mechanisms involved.
Mussel oil is superior to fish oil in preventing atherosclerosis of ApoE−/− mice
Authors: Li Kelei , Song Xiaolei , Li Huiying , Kuang Xiaotong , Liu Shiyi , Liu Run , Li Duo
Published: February 2024

Objectives

The present study aimed to explore the preventive effect of mussel oil (MO) on atherosclerosis and the potential mechanism in apolipoprotein E-null (ApoE−/−) mice.

Methods

ApoE−/− mice were fed with a high-fat and high-cholesterol chow and given corn oil (CO), fish oil (FO), MO, or aspirin (ASP, dissolved in CO) by gavage for 12  weeks. The total n-3 polyunsaturated fatty acids (PUFAs) in MO (51.01%) and FO (46.82%) were comparable (mainly C22:6n-3 and C20:5n-3). Wild-type mice were fed with a normal chow and given equivalent CO as health control (CON).

Results

Compared with the CON group, obvious atherosclerotic plaque appeared at aorta and aortic sinus in the CO group. Compared with the CO group, MO but not FO had a significantly smaller atherosclerotic plaque area in the aorta. The aortic atherosclerotic plaque area was comparable in the MO, CON, and ASP groups. The MO group had a significantly smaller atherosclerotic plaque area, lower lipid deposition, lower contents of smooth muscle cell (SMC), and slightly lower contents of macrophage at the aortic sinus than the FO group. Serum concentrations of IL-1β, NF-κB, and VCAM-1 were comparable in the MO and FO groups and were significantly lower than the CO group. Compared with the CO group, the MO group but not FO group had significantly lower aortic protein levels of p65NF-κB, p38MAPK, and VCAM-1. The aortic protein levels of p-p65NF-κB and p-p38MAPK were significantly lower in the MO group than the FO group.

Conclusion

In conclusion, MO is more potent than FO in preventing atherosclerosis, and the possible mechanism may be by downregulating p38MAPK/NF-κB signaling pathway, decreasing VCAM-1 and macrophage, and inhibiting proliferation and migration of SMC.
Protocol of a first-in-human clinical trial to evaluate the safety, tolerability, and preliminary efficacy of the bispecific CD276xCD3 antibody CC-3 in patients with colorectal cancer (CoRe_CC-3)
Authors: Jung Susanne , Schlenk Richard F. , Hackenbruch Christopher , Roldan Pinzon Sandra S.L. , Bitzer Michael , Pflügler Martin , Walz Juliane S. , Jung Gundram , Heitmann Jonas S. , Salih Helmut R.
Published: February 2024

Introduction

Colorectal cancer (CRC) is the third most common cancer worldwide in men and women. In the metastasized stage, treatment options and prognosis are limited. To address the high medical need of this patient population, we generated a CD276xCD3 bispecific antibody termed CC-3. CD276 is expressed on CRC cells and on tumor vessels, thereby allowing for a “dual” anticancer effect.

Methods and analysis

This first-in-human clinical study is planned as a prospective multicenter trial, enrolling patients with metastatic CRC after three lines of therapy. During the dose-escalation part, initially, an accelerated titration design with single-patient cohorts is employed. Here, each patient will receive a fixed dose level (starting with 50 µg for the first patient); however, between patients, dose level may be increased by up to 100%, depending on the decision of a safety review committee. Upon occurrence of any adverse events (AEs) grade ≥2, dose-limiting toxicity (DLT), or reaching a dose level of ≥800 µg, the escalation will switch to a standard 3 + 3 dose design. After maximum tolerated dose (MTD) has been determined, defined as no more than one of the six patients experiencing DLT, an additional 14 patients receive CC-3 at the MTD level in the dose-expansion phase. Primary endpoints are incidence and severity of AEs, as well as the best objective response to the treatment according to response evaluation criteria in solid tumors (RECIST) 1.1. Secondary endpoints include overall safety, efficacy, survival, quality of life, and pharmacokinetic investigations.

Ethics and dissemination

The CD276xCD3 study was approved by the Ethics Committee of the Medical Faculty of the Heinrich Heine University Düsseldorf and the Paul-Ehrlich-Institut (P00702). Clinical trial results will be published in peer-reviewed journals. Trial registration numbers: ClinicalTrials.cov Registry (NCT05999396) and EU ClinicalTrials Registry (EU trial number 2022-503084-15-00).
The novel LESS (low-cost entrainment syringe system) O2 blender for use in modified bubble CPAP circuits: a clinical study of safety
Authors: Wu Andrew G. , Luch Sreyleak , Slusher Tina M. , Fischer Gwenyth A. , Lunos Scott A. , Bjorklund Ashley R.
Published: February 2024

Background

Bubble continuous positive airway pressure (bCPAP) is used in resource-limited settings for children with respiratory distress. Low-cost modifications of bCPAP use 100% oxygen and may cause morbidity from oxygen toxicity. We sought to test a novel constructible low-cost entrainment syringe system (LESS) oxygen blender with low-cost modified bCPAP in a relevant clinical setting.

Methods

We conducted a clinical trial evaluating safety of the LESS O2 blender among hospitalized children under five years old in rural Cambodia evaluating the rate of clinical failure within one hour of initiation of the LESS O2 blender and monitoring for any other blender-related complications.

Findings

Thirty-two patients were included. The primary outcome (clinical failure) occurred in one patient (3.1%, 95% CI = 0.1–16.2%). Clinical failure was defined as intubation, death, transfer to another hospital, or two of the following: oxygen saturation <85% after 30 min of treatment; new signs of respiratory distress; or partial pressure of carbon dioxide ≥60 mmHg and pH <7.2 on a capillary blood gas. Secondary outcomes included average generated FiO2's with blender use, which were 59% and 52% when a 5 mm entrainment was used vs. a 10 mm entrainment port with 5–7 cm H2O of CPAP and 1–7 L/min (LPM) of flow; and adverse events including loss of CPAP bubbling (64% of all adverse events), frequency of repair or adjustment (44%), replacement (25%), and median time of respiratory support (44 h).

Interpretation

Overall the LESS O2 blender was safe for clinical use. The design could be modified for improved performance including less repair needs and improved nasal interface, which requires modification for the blender to function more consistently.
Real-world effects of Yishen Tongbi decoction for rheumatoid arthritis: protocol for a prospective, observational, multicenter cohort study with validation against double-blind, randomized, controlled trial
Authors: Liu Lijuan , Zhu Fangfang , Xin Yijun , Zhang Lu , Hu Congqi , Xu Yanping , Zhang Jinming , Liu Lingjie , Chen Guangxing
Published: February 2024

Introduction: Rheumatoid arthritis (RA) is a globally challenging and refractory autoimmune disease, constituting a serious menace to human health. RA is characterized by recurrent pain and is difficult to resolve, necessitating prolonged medication for control. Yishen Tongbi decoction is a traditional Chinese herbal compound prescribed for treating RA. We have completed a 3-year RCT study that confirmed the clinical efficacy of Yishen Tongbi decoction for RA. Notably, we observed a faster clinical remission rate compared to MTX by week 4 of treatment. In our forthcoming study, we intend to conduct a comprehensive assessment of the efficacy and safety of Yishen Tongbi decoction in the real-world treatment of RA through a prospective study.

Methods and analysis: This prospective, multicenter, real-world observational study will be conducted at two designated centers in China from October 2023 to August 2025. The study will include 324 patients with active rheumatoid arthritis. One group will receive Yishen Tongbi decoction combined with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). The other group will receive standard treatment. Standard treatment can be further divided into subgroups: csDMARDs, targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), and biologic disease-modifying antirheumatic drugs (bDMARDs). In each group, the number of tender joints, number of swollen joints, pain score, patient global assessment, physician global assessment, disease activity index (DAS28-ESR or DAS28-CRP), clinical disease activity index (cDAI), simplified disease activity index (sDAI) and relevant laboratory data will be compared. Clinical indicators and disease activity of the patients will be assessed at baseline, week 4 and week 12 after the initiation of treatment. The primary outcome will be the American College of Rheumatology 20% improvement criteria (ACR20) attainment rate among patients at week 12 after treatment. Every adverse event will be reported.

Ethics and dissemination: This study has been approved by the Ethics Committee of the first affiliated Hospital of Guangzhou University of traditional Chinese Medicine (NO.K-2023-009). The results of the study will be published in national and international peer-reviewed journals and at scientific conferences. The researchers will inform participants and other RA patients of the results through health education.

Clinical Trial Registration:https://www.chictr.org.cn/index.html, identifier ChiCTR2300076073
Leniolisib: a novel treatment for activated phosphoinositide-3 kinase delta syndrome
Authors: De Surya K.
Published: February 2024

Graphical Abstract

IC50 = 11 nM (PI3Kδ); 244 nM (PI3Kα); 424 nM (PI3Kβ), 2,230 nM (PI3Kγ).
Discovery of a small-molecule NDR1 agonist for prostate cancer therapy
Authors: Bai Yang , Sui Xiuyuan , Xuan Zuodong , Du Yifan , Fu Meiling , Zheng Zeyuan , Yang Kunao , Xu Chunlan , Liu Yankuo , Liu Bin , Zhong Min , Zhang Zhengying , Zheng Jianzhong , Hu Xiaoyan , Zhang Lei , Sun Huimin , Shao Chen
Published: February 2024

Prostatic cancer (PCa) is a common malignant neoplasm in men worldwide. Most patients develop castration-resistant prostate cancer (CRPC) after treatment with androgen deprivation therapy (ADT), usually resulting in death. Therefore, investigating new therapeutic targets and drugs for PCa patients is urgently needed. Nuclear Dbf2-related kinase 1 (NDR1), also known as STK38, is a serine/threonine kinase in the NDR/LATS kinase family that plays a critical role in cellular processes, including immunity, inflammation, metastasis, and tumorigenesis. It was reported that NDR1 inhibited the metastasis of prostate cancer cells by suppressing epithelial-mesenchymal transition (EMT), and decreased NDR1 expression might lead to a poorer prognosis, suggesting the enormous potential of NDR1 in antitumorigenesis. In this study, we characterized a small-molecule agonist named aNDR1, which specifically bound to NDR1 and potently promoted NDR1 expression, enzymatic activity and phosphorylation. aNDR1 exhibited drug-like properties, such as favorable stability, plasma protein binding capacity, cell membrane permeability, and PCa cell-specific inhibition, while having no obvious effect on normal prostate cells. Meanwhile, aNDR1 exhibited good antitumor activity both in vitro and in vivo. aNDR1 inhibited proliferation and migration of PCa cells and promoted apoptosis of PCa cells in vitro. We further found that aNDR1 inhibited subcutaneous tumors and lung metastatic nodules in vivo, with no obvious toxicity to the body. In summary, our study presents a potential small-molecule lead compound that targets NDR1 for clinical therapy of PCa patients.
Exploring spectrum-based descriptors in pharmacological traits through quantitative structure property (QSPR) analysis
Authors: Raza Ali , Munir Muhammad Mobeen
Published: February 2024

The study centered on Quantitative Structure Property Relationship (QSPR) analysis with a focus on various graph energies, investigating drugs like Mefloquinone, Sertraline, Niclosamide, Tizoxanide, PHA-690509, Ribavirin, Emricasan, and Sofosbuvir. Employing computational modeling techniques, the research aimed to uncover the correlations between the chemical structures of these medications and their unique properties. The results illuminated the quantitative relationships between structural characteristics and pharmacological traits, advancing our predictive capabilities. This research significantly contributes to medication discovery and design by providing essential insights into the structure-property connections of these medicinal compounds. Notably, certain spectrum-based descriptors, such as positive inertia energy, adjacency energy, arithmetic-geometric energy, first zegrab energy, and the harmonic index, exhibited strong correlation coefficients above 0.999. In contrast, well-known descriptors like the Extended adjacency, Laplacian and signless Laplacian spectral radii, and the first and second Zagreb Estrada indices showed weaker performance. The article emphasizes the application of graph energies and a linear regression model to predict pharmacological features effectively, enhancing the drug discovery process and aiding in targeted drug design by elucidating the relationship between molecular structure and pharmacological characteristics.
Salinity change evokes stress and immune responses in Atlantic salmon with microalgae showing limited potential for dietary mitigation
Authors: van Muilekom Doret R. , Mueller Jonas , Lindemeyer Jacqueline , Schultheiß Thekla , Maser Edmund , Seibel Henrike , Rebl Alexander , Schulz Carsten , Goldammer Tom
Published: February 2024

Smoltification was found to impact both immune and stress responses of farmed Atlantic salmon (Salmo salar), but little is known about how salinity change affects salmon months after completed smoltification. Here, we examined (1) the effect of salinity change from brackish water to seawater on the stress and immune responses in Atlantic salmon and (2) evaluated if functional diets enriched with microalgae can mitigate stress- and immune-related changes. Groups of Atlantic salmon were fed for 8 weeks with different microalgae-enriched diets in brackish water and were then transferred into seawater. Samples of the head kidney, gill, liver and plasma were taken before seawater transfer (SWT), 20 h after SWT, and 2 weeks after SWT for gene-expression analysis, plasma biochemistry and protein quantification. The salmon showed full osmoregulatory ability upon transfer to seawater reflected by high nkaα1b levels in the gill and tight plasma ion regulation. In the gill, one-third of 44 investigated genes were reduced at either 20 h or 2 weeks in seawater, including genes involved in cytokine signaling (il1b) and antiviral defense (isg15, rsad2, ifit5). In contrast, an acute response after 20 h in SW was apparent in the head kidney reflected by increased plasma stress indicators and induced expression of genes involved in acute-phase response (drtp1), antimicrobial defense (camp) and stress response (hspa5). However, after 2 weeks in seawater, the expression of antiviral genes (isg15, rsad2, znfx1) was reduced in the head kidney. Few genes (camp, clra, c1ql2) in the gill were downregulated by a diet with 8% inclusion of Athrospira platensis. The results of the present study indicate that salinity change months after smoltification evokes molecular stress- and immune responses in Atlantic salmon. However, microalgae-enriched functional diets seem to have only limited potential to mitigate the related changes.
Combining machine learning and remote sensing-integrated crop modeling for rice and soybean crop simulation
Authors: Ko Jonghan , Shin Taehwan , Kang Jiwoo , Baek Jaekyeong , Sang Wan-Gyu
Published: February 2024

Machine learning (ML) techniques offer a promising avenue for improving the integration of remote sensing data into mathematical crop models, thereby enhancing crop growth prediction accuracy. A critical variable for this integration is the leaf area index (LAI), which can be accurately assessed using proximal or remote sensing data based on plant canopies. This study aimed to (1) develop a machine learning-based method for estimating the LAI in rice and soybean crops using proximal sensing data and (2) evaluate the performance of a Remote Sensing-Integrated Crop Model (RSCM) when integrated with the ML algorithms. To achieve these objectives, we analyzed rice and soybean datasets to identify the most effective ML algorithms for modeling the relationship between LAI and vegetation indices derived from canopy reflectance measurements. Our analyses employed a variety of ML regression models, including ridge, lasso, support vector machine, random forest, and extra trees. Among these, the extra trees regression model demonstrated the best performance, achieving test scores of 0.86 and 0.89 for rice and soybean crops, respectively. This model closely replicated observed LAI values under different nitrogen treatments, achieving Nash-Sutcliffe efficiencies of 0.93 for rice and 0.97 for soybean. Our findings show that incorporating ML techniques into RSCM effectively captures seasonal LAI variations across diverse field management practices, offering significant potential for improving crop growth and productivity monitoring.
Application of the strip clear-cutting system in a running bamboo (Phyllostachys glauca McClure) forest: feasibility and sustainability assessments
Authors: Liang Kuan , Wang Guangru , Shen Zhan , Wu Juan , Zou Na , Yu Hongying , Yu Shebao , Chen Fusheng , Shi Jianmin
Published: February 2024

Introduction

As a renewable forest resource, bamboo plays a role in sustainable forest development. However, traditional cutting systems, selection cutting (SeC) and clear-cutting (ClC), result in an unsustainable production of bamboo forests due to labor-consuming or bamboo degradation. Recently, a strip clear-cutting (StC) was theoretically proposed to promote the sustainability of bamboo production, while little is known about its application consequence.

Methods

Based on a 6-year experiment, we applied the strip clear-cutting system in a typical running bamboo (Phyllostachys glauca McClure) forest to assess its feasibility and sustainability. Using SeC and ClC as controls, we set three treatments with different strip widths (5 m, 10 m, and 20 m) for strip clear-cutting, simplified as StC-5, StC-10, and StC-20, respectively. Then, we investigated leaf physiological traits, bamboo size and productivity, population features, and economic benefits for all treatments.

Results

The stands managed by StC had high eco-physiological activities, such as net photosynthetic rate (Pn), photosynthetic nitrogen use efficiency (PNUE), and photosynthetic phosphorus use efficiency (PPUE), and thus grew well, achieved a large diameter at breast height (DBH), and were tall. The stand biomass of StC (8.78 t hm-2 year-1) was 1.19-fold and 1.49-fold greater than that of SeC and ClC, respectively, and StC-10 and StC-20 were significantly higher than SeC or ClC (p< 0.05). The income and profit increased with the increase in stand density and biomass, and StC-20 and StC-10 were significantly higher than SeC or ClC (p< 0.05). Using principal components analysis and subordinate function analysis, we constructed a composite index to indicate the sustainability of bamboo forests. For the sustainability assessment, StC-10 had the highest productive sustainability (0.59 ± 0.06) and the second highest economic sustainability (0.59 ± 0.11) in all cutting treatments. StC-10 had the maximum overall sustainability, with a value of 0.53 ± 0.02, which was significantly higher than that of ClC (p< 0.05).

Conclusion

The results verified that StC for Phyllostachys glauca forests is feasible and sustainable as its sustainability index outweighs those of traditional cutting systems (SeC and ClC), and 10 m is the optimum distance for the strip width of StC. Our findings provide a new cutting system for managing other running bamboo forests sustainably.
Phylogenetic diversity drives soil multifunctionality in arid montane forest-grassland transition zone
Authors: Wang Xiaofei , Gong Lu , Luo Yan , Ding Zhaolong , Guo Qian , Li Xiaochen , Ma Xinyu
Published: February 2024

Exploring plant diversity and ecosystem functioning in different dimensions is crucial to preserve ecological balance and advance ecosystem conservation efforts. Ecosystem transition zones serve as vital connectors linking two distinct ecosystems, yet the impact of various aspects of plant diversity (including taxonomic, functional, and phylogenetic diversity) on soil multifunctionality in these zones remains to be clarified. This study focuses on the forest-grassland transition zone in the mountains on the northern slopes of the Tianshan Mountains, and investigates vegetation and soil characteristics from forest ecosystems to grassland ecosystems to characterize plant diversity and soil functioning, as well as the driving role of plant diversity in different dimensions. In the montane forest-grassland transition zone, urease (URE) and total nitrogen (TN) play a major role in regulating plant diversity by affecting the soil nutrient cycle. Phylogenetic diversity was found to be the strongest driver of soil multifunctionality, followed by functional diversity, while taxonomic diversity was the least important driver. Diverse species were shown to play an important role in maintaining soil multifunctionality in the transition zone, especially distantly related species with high phylogeny. The study of multidimensional plant diversity and soil multifunctionality in the montane forest-grassland transition zone can help to balance the relationship between these two elements, which is crucial in areas where the ecosystem overlaps, and the application of the findings can support sustainable development in these regions.
We need to talk: a qualitative inquiry into pathways to care for young men at ultra-high risk for psychosis
Authors: Åmlid Håkon Olav , Carlsson Jan , Bjørnestad Jone , Joa Inge , Hegelstad Wenche ten Velden
Published: February 2024

Introduction

It is known from the literature that men are slower to seek help and staying engaged in mental health care compared to women. Seeing that in psychosis, men more often than women have insidious onsets but also a more malign illness course, it is important to find ways to improve timely help-seeking. The aim of this study was to explore barriers and facilitators for help-seeking in young male persons struggling with early signs of psychosis.

Methods

Qualitative interviews with nine young men who suffer from a first episode of psychosis or psychosis risk symptoms.

Results

Male stereotypical ideals, significant others, and knowledge of symptoms and where to get help as well characteristics of symptom trajectories appeared to be important determinants of help-seeking behavior.

Discussion

Interviews indicated that help-seeking in the participants was delayed first, because of reluctancy to disclose distress and second, because significant others were unable to accurately recognize symptoms. Information, awareness, and easy access to care remain important in early detection and intervention in psychosis and psychosis risk. However, more emphasis should be placed on de-stigmatizing mental health problems in men and aiming information specifically at them.
Exploring second language students’ language assessment literacy: impact on test anxiety and motivation
Authors: Weng Fanrong , Liu Xingnan
Published: February 2024

Introduction

This research aims to investigate the impact of students’ language assessment literacy (LAL) on their cognition. The study specifically examines how different levels of LAL influence two critical factors: test anxiety and motivation to learn a second language.

Methods

To achieve the research objectives, a questionnaire was administered to a sample of 415 university students in China. The questionnaire utilized a five-point Likert scale to assess students’ levels of LAL, test anxiety, and motivation to learn a second language. Descriptive data were examined to reveal students’ proficiency in LAL, along with their levels of test anxiety and motivation. Multilevel regression analyses were performed using Mplus to investigate whether students’ LAL proficiency can predict their levels of test anxiety and motivation.

Results

The findings indicated that the participating students had a proficiency level of approximately 60% in the content of the LAL questionnaire. The analysis further revealed the relationships between specific dimensions of LAL and both test anxiety and second language motivation. The multilevel regression analysis suggested that theoretical knowledge about language and language learning, the understanding of the impact and social value of language assessments, and the uses of assessments to enhance learning, positively predicted students’ extrinsic motivation. Furthermore, students’ understanding of the uses of assessments to learn and their theoretical knowledge about language learning were identified as positive predictors of intrinsic motivation. Additionally, it was observed that students’ LAL did not significantly predict test anxiety.

Discussion

These findings emphasize the significance of enhancing students’ LAL due to the identified relationships between LAL dimensions and motivation to learn a second language. The study suggests pedagogical implications for improving LAL, with a focus on specific dimensions that positively impact students’ motivation. The absence of a significant relationship between LAL dimensions and test anxiety prompts further exploration and consideration of additional factors influencing students’ anxiety in language assessments.
Current situation and influencing factors of each turnover of kindergarten teachers – a questionnaire survey
Authors: Ren Xiaoling , Yan Zhonglian , Zhang Zedong , Chen Jiewen , Tian Yun
Published: February 2024

Objective

Frequent teacher turnover may damage the development of teachers and the regular operation of kindergartens. This original research presented kindergarten teachers’ first, second, and third turnover rates and occurrence times. This research analyzed the relationship between socio-demographic variables and the varying frequency of kindergarten teacher turnover. These data were used to investigate the characteristics of first, second, and third kindergarten turnover. This research evaluated kindergarten teachers’ occupational ambition, emotional attachment, and self-efficacy. Likewise, this research also analyzed the social context, organizational support, management mechanism, reward, and occupational stress of kindergarten. These data were used to determine the key factors affecting kindergarten teachers’ turnover.

Methods

This research recruited 1,118 kindergarten teachers (mean age = 31.67, sd = 5.02; 3.85% male, 96.14% female) from China. Based on the existing scales, this research developed the Questionnaire of Kindergarten Teachers’ Turnover and Influencing Factors for the survey. Kindergarten teachers reported basic information and the impact factors of their first, second, and third turnover through online questionnaires. The Chi-square test was used to analyze the correlation between socio-demographic variables and different frequencies of kindergarten teacher turnover. The binary logistic regression explored the eight factors affecting kindergarten teachers’ first, second, and third turnover.

Results

The results showed that 43.65% of kindergarten teachers had resigned. In detail, 25.60% of kindergarten teachers resigned once, 10.64% of kindergarten teachers resigned twice, and 8.41% of kindergarten teachers resigned thrice. Gender and marital status were significantly correlated with the three frequencies of kindergarten teacher turnover. Occupational stress, reward, management mechanisms, and ambition consistently affected kindergarten teachers’ first, second, and third turnover.

Conclusion

The relevant management departments should pay attention to the high turnover rate of kindergarten teachers and put forward more strategies to improve their stability. Women and married can be favored in the recruitment of kindergarten teachers. It is crucial to reduce pressure and improve rewards for kindergarten teachers. Also, kindergartens should provide the space to display teachers’ talents and improve management mechanisms. These results provide empirical support for proposing effective policies to promote the stability of kindergarten teachers’ construction.
A double-blind randomized clinical trial on the suggestive effect of anxiety management questionnaires in dental emergencies
Authors: Benz Carla Irene , Wolanski Celina , Piefke Martina , Campus Guglielmo , Piwowarczyk Andree , Wolf Thomas Gerhard
Published: February 2024

Objective

Dental anxiety is widespread among both children and adults. To diagnose dental anxiety, standardized anxiety questionnaires are recommended. Based on the suggestive nature of the questionnaires, the study aimed to find out whether asking respondents about personal coping strategies before dental treatment influences their anxiety.

Methods

This prospective, double-blind, randomized controlled clinical trial included a total of 158 patients of a university dental clinic on emergency service. The intervention group (n = 82) received the Coping with Anxiety Questionnaire (CAQ) and the control group (n = 76) the Hierarchical Anxiety Questionnaire (HAF). State anxiety scores were assessed by using the State–Trait Anxiety Inventory (STAI) before and after the completion of each questionnaire.

Results

Anxiety decreased in the intervention group (CAQ) (p < 0.001) and increased in the control group (HAF) (p < 0.001).

Conclusion

Within the limitations of the current study, a diagnostic tool of a standardized questionnaire for the assessment to assess personal coping strategies decreased state anxiety in comparison to a questionnaire assessing anxiety.

Clinical trial registration

https://www.drks.de, German Trials Register (DRKS00032450).