bluuebunny/crossref_metadata_2025 huggingface dataset:
Nisin-based therapy: a realistic and eco-friendly biocontrol strategy to contrast Xylella fastidiosa subsp. pauca infections in planta
Authors: Sabri Miloud , El Handi Kaoutar , Valentini Franco , De Stradis Angelo , Cara Orges , Calvano Cosima Damiana , Bianco Mariachiara , Trani Antonio , Elbeaino Toufic
Published: May 2024

The lack of sustainable strategies for combating Xylella fastidiosa (Xf) highlights the pressing need for novel practical antibacterial tools. In this study, Lactococcus lactis subsp. lactis strain ATCC 11454 (L. lactis), known for its production of nisin A, was in vitro tested against Xf subsp. pauca. Preliminary investigations showed that nisin A was involved in a strong antagonistic activity exhibited by L. lactis against Xf. Thus, the efficacy of nisin A was comprehensively assessed through a combination of in vitro and in planta experiments. In vitro investigations employing viable-quantitative PCR, spot assay, turbidity reduction assay, fluorescence microscopy, and transmission electron microscopy demonstrated nisin’s robust bactericidal effect on Xf at a minimal lethal concentration of 0.6 mg/mL. Moreover, results from fluorescence and transmission electron microscopies indicated that nisin directly and rapidly interacts with the membranes of Xf cells, leading to the destruction of bacterial cells in few minutes. In in planta tests, nisin also demonstrated the ability to tackle Xf infections within Nicotiana benthamiana plants that remained asymptomatic 74 days post inoculation. Furthermore, RPLC-ESI-MS/MS analyses showed that nisin translocated to all parts of the plants and remains intact for up to 9 days. For the first time, this study underscores the nisin-based strategy as a realistic and eco-friendly approach to be further investigated against Xf infections in the field.
Seeing beyond the symptoms: biomarkers and brain regions linked to cognitive decline in Alzheimer’s disease
Authors: Hojjati Seyed Hani , Babajani-Feremi Abbas ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: May 2024

Objective

Early Alzheimer’s disease (AD) diagnosis remains challenging, necessitating specific biomarkers for timely detection. This study aimed to identify such biomarkers and explore their associations with cognitive decline.

Methods

A cohort of 1759 individuals across cognitive aging stages, including healthy controls (HC), mild cognitive impairment (MCI), and AD, was examined. Utilizing nine biomarkers from structural MRI (sMRI), diffusion tensor imaging (DTI), and positron emission tomography (PET), predictions were made for Mini-Mental State Examination (MMSE), Clinical Dementia Rating Scale Sum of Boxes (CDRSB), and Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS). Biomarkers included four sMRI (e.g., average thickness [ATH]), four DTI (e.g., mean diffusivity [MD]), and one PET Amyloid-β (Aβ) measure. Ensemble regression tree (ERT) technique with bagging and random forest approaches were applied in four groups (HC/MCI, HC/AD, MCI/AD, and HC/MCI/AD).

Results

Aβ emerged as a robust predictor of cognitive scores, particularly in late-stage AD. Volumetric measures, notably ATH, consistently correlated with cognitive scores across early and late disease stages. Additionally, ADAS demonstrated links to various neuroimaging biomarkers in all subject groups, highlighting its efficacy in monitoring brain changes throughout disease progression. ERT identified key brain regions associated with cognitive scores, such as the right transverse temporal region for Aβ, left and right entorhinal cortex, left inferior temporal gyrus, and left middle temporal gyrus for ATH, and the left uncinate fasciculus for MD.

Conclusion

This study underscores the importance of an interdisciplinary approach in understanding AD mechanisms, offering potential contributions to early biomarker development.
Failure of senolytic treatment to prevent cognitive decline in a female rodent model of aging
Authors: Rani Asha , Bean Linda , Budamagunta Vivekananda , Kumar Ashok , Foster Thomas C.
Published: May 2024

There are sex differences in vulnerability and resilience to the stressors of aging and subsequent age-related cognitive decline. Cellular senescence occurs as a response to damaging or stress-inducing stimuli. The response includes a state of irreversible growth arrest, the development of a senescence-associated secretory phenotype, and the release of pro-inflammatory cytokines associated with aging and age-related diseases. Senolytics are compounds designed to eliminate senescent cells. Our recent work indicates that senolytic treatment preserves cognitive function in aging male F344 rats. The current study examined the effect of senolytic treatment on cognitive function in aging female rats. Female F344 rats (12 months) were treated with dasatinib (1.2 mg/kg) + quercetin (12 mg/kg) or ABT-263 (12 mg/kg) or vehicle for 7 months. Examination of the estrus cycle indicated that females had undergone estropause during treatment. Senolytic treatment may have increased sex differences in behavioral stress responsivity, particularly for the initial training on the cued version of the watermaze. However, pre-training on the cue task reduced stress responsivity for subsequent spatial training and all groups learned the spatial discrimination. In contrast to preserved memory observed in senolytic-treated males, all older females exhibited impaired episodic memory relative to young (6-month) females. We suggest that the senolytic treatment may not have been able to compensate for the loss of estradiol, which can act on aging mechanisms for anxiety and memory independent of cellular senescence.
Harnessing ferroic ordering in thin film devices for analog memory and neuromorphic computing applications down to deep cryogenic temperatures
Authors: Majumdar Sayani
Published: May 2024

The future computing beyond von Neumann era relies heavily on emerging devices that can extensively harness material and device physics to bring novel functionalities and can perform power-efficient and real time computing for artificial intelligence (AI) tasks. Additionally, brain-like computing demands large scale integration of synapses and neurons in practical circuits that requires the nanotechnology to support this hardware development, and all these should come at an affordable process complexity and cost to bring the solutions close to market rather soon. For bringing AI closer to quantum computing and space technologies, additional requirements are operation at cryogenic temperatures and radiation hardening. Considering all these requirements, nanoelectronic devices utilizing ferroic ordering has emerged as one promising alternative. The current review discusses the basic architectures of spintronic and ferroelectric devices for their integration in neuromorphic and analog memory applications, ferromagnetic and ferroelectric domain structures and control of their dynamics for reliable multibit memory operation, synaptic and neuronal leaky-integrate-and-fire (LIF) functions, concluding with their large-scale integration possibilities, challenges and future research directions.
The therapeutic potential of microRNAs to ameliorate spinal cord injury by regulating oligodendrocyte progenitor cells and remyelination
Authors: Qiu Shanru , Dai Hui , Wang Yu , Lv Yehua , Yu Bin , Yao Chun
Published: May 2024

Spinal cord injury (SCI) can cause loss of sensory and motor function below the level of injury, posing a serious threat to human health and quality of life. One significant characteristic feature of pathological changes following injury in the nervous system is demyelination, which partially contributes to the long-term deficits in neural function after injury. The remyelination in the central nervous system (CNS) is mainly mediated by oligodendrocyte progenitor cells (OPCs). Numerous complex intracellular signaling and transcriptional factors regulate the differentiation process from OPCs to mature oligodendrocytes (OLs) and myelination. Studies have shown the importance of microRNA (miRNA) in regulating OPC functions. In this review, we focus on the demyelination and remyelination after SCI, and summarize the progress of miRNAs on OPC functions and remyelination, which might provide a potential therapeutic target for SCI treatments.
Alzheimer’s disease and oral manifestations: a bi-directional Mendelian randomization study
Authors: Huang Jingxuan , Deng Aiping , Bai Yunshuang , Li Chunyu , Shang Huifang
Published: May 2024

Background

Epidemiological studies have provided evidence suggesting an association between Alzheimer’s disease (AD) and various oral manifestations. However, conflicting conclusions have been drawn, and whether a causal association truly exists remains unclear.

Methods

In order to investigate the potential causal association between AD and prevalent oral diseases, we conducted a bi-directional two-sample Mendelian randomization analysis based on summary statistics from genome-wide association studies of AD (N = 63,926), as well as mouth ulcer (N = 461,103), oral cavity cancer (N = 4,151), and periodontal disease (N = 527,652).

Results

We identified that one standard increase in the risk of AD was causally associated with a reduced risk of oral cavity cancer (OR = 0.76, 95% CI: 0.63–0.92, p = 3.73 × 10−3). In the opposite direction, oral conditions were not causally associated with risk of AD.

Conclusion

The present findings contributed to a better understanding of the correlation between AD and oral conditions, specifically oral cavity cancer. These results also identified new avenues for exploring the underlying mechanisms of oral cavity cancer.
Comparison of two automated CT perfusion software packages in patients with ischemic stroke presenting within 24 h of onset
Authors: Kim Nakhoon , Ha Sue Young , Park Gi-Hun , Park Jong-Hyeok , Kim Dongmin , Sunwoo Leonard , Kye Min-Surk , Baik Sung Hyun , Jung Cheolkyu , Ryu Wi-Sun , Kim Beom Joon
Published: May 2024

Background

We compared the ischemic core and hypoperfused tissue volumes estimated by RAPID and JLK-CTP, a newly developed automated computed tomography perfusion (CTP) analysis package. We also assessed agreement between ischemic core volumes by two software packages against early follow-up infarct volumes on diffusion-weighted images (DWI).

Methods

This retrospective study analyzed 327 patients admitted to a single stroke center in Korea from January 2021 to May 2023, who underwent CTP scans within 24 h of onset. The concordance correlation coefficient (ρ) and Bland–Altman plots were utilized to compare the volumes of ischemic core and hypoperfused tissue volumes between the software packages. Agreement with early (within 3 h from CTP) follow-up infarct volumes on diffusion-weighted imaging (n = 217) was also evaluated.

Results

The mean age was 70.7 ± 13.0 and 137 (41.9%) were female. Ischemic core volumes by JLK-CTP and RAPID at the threshold of relative cerebral blood flow (rCBF) < 30% showed excellent agreement (ρ = 0.958 [95% CI, 0.949 to 0.966]). Excellent agreement was also observed for time to a maximum of the residue function (Tmax) > 6 s between JLK-CTP and RAPID (ρ = 0.835 [95% CI, 0.806 to 0.863]). Although early follow-up infarct volume showed substantial agreement in both packages (JLK-CTP, ρ = 0.751 and RAPID, ρ = 0.632), ischemic core volumes at the threshold of rCBF <30% tended to overestimate ischemic core volumes.

Conclusion

JLK-CTP and RAPID demonstrated remarkable concordance in estimating the volumes of the ischemic core and hypoperfused area based on CTP within 24 h from onset.
Case report: Early-onset Parkinson’s disease with lower limb spasticity in a new DJ-1/PARK7 patient
Authors: Fujita Masako , Nishijima Haruo , Katagai Atsuko , Suzuki Chieko , Hattori Nobutaka , Tomiyama Masahiko
Published: May 2024

Rare autosomal recessive variants in DJ-1, a causative gene for early-onset Parkinson’s disease, have been associated with a variety of clinical syndromes in a limited number of patients. Here, we report a case of a novel DJ-1 variant in a 39-year-old man with a 4-year history of parkinsonism, cognitive dysfunction, and lower limb spasticity. He was diagnosed with Parkinson’s disease. Genetic testing of the patient revealed compound heterozygous variants in the DJ-1 gene (exon 6 deletion + c.242dup), of which exon 6 deletion was a novel variant. We conclude that variants in DJ-1 should be considered possible causes of early-onset parkinsonism with spasticity and cognitive impairment, as in this case.
Neuroligin-1 dependent phosphotyrosine signaling in excitatory synapse differentiation
Authors: Szíber Zsófia , Drouet Adèle , Mondin Magali , Levet Florian , Thoumine Olivier
Published: May 2024

Introduction

The synaptic adhesion molecule neuroligin-1 (NLGN1) is involved in the differentiation of excitatory synapses, but the precise underlying molecular mechanisms are still debated. Here, we explored the role of NLGN1 tyrosine phosphorylation in this process, focusing on a subset of receptor tyrosine kinases (RTKs), namely FGFR1 and Trks, that were previously described to phosphorylate NLGN1 at a unique intracellular residue (Y782).

Methods

We used pharmacological inhibitors and genetic manipulation of those RTKs in dissociated hippocampal neurons, followed by biochemical measurement of NLGN1 phosphorylation and immunocytochemical staining of excitatory synaptic scaffolds.

Results

This study shows that: (i) the accumulation of PSD-95 at de novo NLGN1 clusters induced by neurexin crosslinking is reduced by FGFR and Trk inhibitors; (ii) the increase in PSD-95 puncta caused by NLGN1 over-expression is impaired by FGFR and Trk inhibitors; (iii) TrkB activation by BDNF increases NLGN1 phosphorylation; and (iv) TrkB knock-down impairs the increase of PSD-95 puncta caused by NLGN1 over-expression, an effect which is not seen with the NLGN1 Y782A mutant.

Discussion

Together, our data identify TrkB as one of the major RTKs responsible for NLGN1 tyrosine phosphorylation, and reveal that TrkB activity is necessary for the synaptogenic effects of NLGN1.
Collagen-derived dipeptide prolyl-hydroxyproline cooperates with Foxg1 to activate the PGC-1α promoter and induce brown adipocyte-like phenotype in rosiglitazone-treated C3H10T1/2 cells
Authors: Nomura Kaho , Kimira Yoshifumi , Kobayashi Ryosuke , Shiobara Yuna , Osawa Yoshihiro , Kataoka-Matsushita Aya , Shimizu Jun , Wada Masahiro , Mano Hiroshi
Published: May 2024

Background

The global obesity epidemic is a significant public health issue, often leading to metabolic disorders such as diabetes and cardiovascular diseases. Collagen peptides (CP) and their bioactive component, Prolyl-hydroxyproline (Pro-Hyp), have shown potential in reducing adipocyte size, with unclear mechanisms concerning brown adipocyte differentiation.

Methods

We investigated the effects of Pro-Hyp on the differentiation of brown adipocytes in C3H10T1/2 mesenchymal stem cells, focusing on its impact on adipocyte size, gene expression related to brown fat function, and mitochondrial activity.

Results

Pro-Hyp treatment decreased adipocyte size and upregulated brown fat-specific genes, including C/EBPα, PGC-1α, and UCP-1. Remarkably, it did not alter PPARγ expression. Pro-Hyp also elevated mitochondrial activity, suggesting enhanced brown adipocyte functionality. A Pro-Hyp responsive element was identified in the PGC-1α gene promoter, which facilitated the binding of the Foxg1 transcription factor, indicating a novel regulatory mechanism.

Conclusion

Pro-Hyp promotes brown adipocyte differentiation, potentially offering a therapeutic strategy for obesity management. This study provides a molecular basis for the anti-obesity effects of CP, although further in vivo studies are needed to confirm these findings and to investigate the potential impact on beige adipocyte differentiation.
Development of a screener to assess athlete risk behavior of not using third-party tested nutritional supplements
Authors: Wardenaar Floris C. , Schott Kinta D. , Seltzer Ryan G. N. , Gardner Christopher D.
Published: May 2024

Introduction

The aim of this cross-sectional study was to develop an algorithm to predict athletes use of third-party tested (TPT) supplements. Therefore, a nutritional supplement questionnaire was used with a section about self-reported TPT supplement use.

Methods

Outcomes were randomly assigned to a training dataset to identify predictors using logistic regression models, or a cross-validation dataset. Training data were used to develop an algorithm with a score from 0 to 100 predicting use or non-use of TPT nutritional supplements.

Results

A total of n = 410 NCAA Division I student-athletes (age: 21.4 ± 1.6 years, 53% female, from >20 sports) were included. Then n = 320 were randomly selected, of which 34% (n = 109) of users consistently reported that all supplements they used were TPT. Analyses resulted in a 10-item algorithm associated with use or non-use of TPT. Risk quadrants provided the best fit for classifying low vs. high risk toward inconsistent TPT-use resulting in a cut-off ≥60% (χ2(4) = 61.26, P < 0.001), with reasonable AUC 0.78. There was a significant association for TPT use (yes/no) and risk behavior (low vs. high) defined from the algorithm (χ2(1)=58.6, P < 0.001). The algorithm had a high sensitivity, classifying 89% of non-TPT users correctly, while having a low specificity, classifying 49% of TPT-users correctly. This was confirmed by cross-validation (n = 34), reporting a high sensitivity (83%), despite a lower AUC (0.61).

Discussion

The algorithm classifies high-risk inconsistent TPT-users with reasonable accuracy, but lacks the specificity to classify consistent users at low risk. This approach should be useful in identifying athletes that would benefit from additional counseling.
Efficacy and safety of robotic radical hysterectomy in cervical cancer compared with laparoscopic radical hysterectomy: a meta-analysis
Authors: Dai Zhen , Qin Fuqiang , Yang Yuxing , Liang Weiming , Wang Xiao
Published: May 2024

Introduction

Robotic radical hysterectomy (RRH) is a newly developed minimally invasive surgery that has been suggested as a substitute for laparoscopic radical hysterectomy (LRH). This meta-analysis aims to assess the clinical efficacy and safety of robot-assisted radical hysterectomy (RRH) for cervical cancer.

Materials and methods

A systematic search was conducted in four databases (Medline, Embase, Web of Science, and CENTRAL) for studies comparing the utilization of RRH and LRH in the treatment of cervical cancer. The search included articles published from the inception of the databases up until July 18, 2023. Meta-analyses were conducted to assess several surgical outcomes, including operation time, estimated blood loss, length of hospital stay, pelvic lymph nodes, positive surgical margin, total complications, one-year recurrence rate, one-year mortality, and one-year disease-free survival rate.

Results

Six studies were included for meta-analysis. In total, 234 patients were in the RRH group and 174 patients were in the LRH group. RRH had significantly longer operative time (MD=14.23,95% CI:5.27~23.20, P=0.002),shorter hospital stay (MD= -1.10,95% CI:-1.43~0.76, P <0.00001),more dissected pelvic lymph nodes(MD=0.89,95%CI:0.18~1.60, P =0.01) and less blood loss(WMD = -27.78,95%CI:-58.69 ~ -3.14, P=0.08, I2 = 80%) compared with LRH. No significant difference was observed between two groups regarding positive surgical margin (OR = 0.59, 95% CI 0.18~2.76, P=0.61), over complications (OR = 0.77, 95% CI, 0.46-1.28, P=0.31), one-year recurrence rate (OR = 0.19, 95% CI 0.03-1.15, P=0.13), one-year mortality rate (OR = 0.19, 95% CI 0.03-1.15, P=0.07) and disease-free survival at one year (OR = 1.92, 95% CI 0.32-11.50, P=0.48).

Conclusion

RRH is an increasingly popular surgical method known for its high level of security and efficiency. It has many benefits in comparison to LRH, such as decreased blood loss, a higher quantity of dissected pelvic lymph nodes, and a shorter duration of hospitalization. Further multicenter, randomized controlled trials with extended follow-up durations are necessary to conclusively determine the safety and efficacy of RRH, as no significant differences were observed in terms of positive surgical margin, postoperative complications, 1-year recurrence, 1-year mortality, and 1-year disease-free survival.

Systematic Review Registration

PROSPERO, identifier CRD42023446653
Molecular profiling of metastatic breast cancer and target-based therapeutic matching in an Asian tertiary phase I oncology unit
Authors: Walsh Robert John , Ong Rebecca , Cheo Seng Wee , Low Peter Q.J. , Jayagopal Aishwarya , Lee Matilda , Ngoi Natalie , Ow Samuel G. , Wong Andrea L.A. , Lim Siew Eng , Lim Yi Wan , Heong Valerie , Sundar Raghav , Soo Ross A. , Chee Cheng Ean , Yong Wei Peng , Goh Boon Cher , Lee Soo Chin , Tan David S.P. , Lim Joline S.J.
Published: May 2024

Introduction

Molecular profiling of metastatic breast cancer (MBC) through the widespread use of next-generation sequencing (NGS) has highlighted actionable mutations and driven trials of targeted therapy matched to tumour molecular profiles, with improved outcomes reported using such an approach. Here, we review NGS results and treatment outcomes for a cohort of Asian MBC patients in the phase I unit of a tertiary centre.

Methods

Patients with MBC referred to a phase I unit underwent NGS via Ion AmpliSeq Cancer Hotspot v2 (ACH v2, 2014–2017) prior to institutional change to FoundationOne CDx (FM1; 2017–2022). Patients were counselled on findings and enrolled on matched therapeutic trials, where available. Outcomes for all subsequent treatment events were recorded to data cut-off on January 31, 2022.

Results

A total of 215 patients were enrolled with successful NGS in 158 patients. The PI3K/AKT/PTEN pathway was the most altered with one or more of the pathway member genes PIK3/AKT/PTEN affected in 62% (98/158) patients and 43% of tumours harbouring a PIK3CA alteration. Tumour mutational burden (TMB) was reported in 96/109 FM1 sequenced patients, with a mean TMB of 5.04 mt/Mb and 13% (12/96) with TMB ≥ 10 mt/Mb. Treatment outcomes were evaluable in 105/158 patients, with a pooled total of 216 treatment events recorded. Matched treatment was administered in 47/216 (22%) events and associated with prolonged median progression-free survival (PFS) of 21.0 weeks [95% confidence interval (CI) 11.7, 26.0 weeks] versus 12.1 weeks (95% CI 10.0, 15.4 weeks) in unmatched, with hazard ratio (HR) for progression or death of 0.63 (95% CI 0.41, 0.97; p = 0.034). In the subgroup of PIK3/AKT/PTEN-altered MBC, the HR for progression or death was 0.57 (95% CI 0.35, 0.92; p = 0.02), favouring matched treatment. Per-patient overall survival (OS) analysis (n = 105) showed improved survival for patients receiving matched treatment versus unmatched, with median OS (mOS) of 30.1 versus 11.8 months, HR = 0.45 (95% CI 0.24, 0.84; p = 0.013). Objective response rate (ORR) in the overall population was similar in matched and unmatched treatment events (23.7% versus 17.2%, odds ratio of response 1.14 95% CI 0.50, 2.62; p = 0.75).

Conclusions

Broad-panel NGS in MBC is feasible, allowing therapeutic matching, which was associated with improvements in PFS and OS.
4-nitroquinoline 1-oxide-induced oral epithelial lesions exhibit time- and stage-dependent changes in the tumor immune microenvironment
Authors: Sellæg Kjersti , Schwienbacher Ruth , Kranz Mathias , Aamodt Anna Engan , Wirsing Anna M. , Berge Gerd , Hadler-Olsen Elin , Magnussen Synnøve Norvoll
Published: May 2024

Oral tongue squamous cell carcinoma (OTSCC) is the most common cancer of the oral cavity and is associated with high morbidity due to local invasion and lymph node metastasis. Tumor infiltrating lymphocytes (TILs) are associated with good prognosis in oral cancer patients and dictate response to treatment. Ectopic sites for immune activation in tumors, known as tertiary lymphoid structures (TLS), and tumor-associated high-endothelial venules (TA-HEVs), which are specialized lymphocyte recruiting vessels, are associated with a favorable prognosis in OSCC. Why only some tumors support the development of TLS and HEVs is poorly understood. In the current study we explored the infiltration of lymphocyte subsets and the development of TLS and HEVs in oral epithelial lesions using the 4-nitroquinoline 1-oxide (4NQO)-induced mouse model of oral carcinogenesis. We found that the immune response to 4NQO-induced oral epithelial lesions was dominated by T cell subsets. The number of T cells (CD4+, FoxP3+, and CD8+), B cells (B220+) and PNAd+ HEVs increased from the earliest to the latest endpoints. All the immune markers increased with the severity of the dysplasia, while the number of HEVs and B cells further increased in SCCs. HEVs were present already in early-stage lesions, while TLS did not develop at any timepoint. This suggests that the 4NQO model is applicable to study the dynamics of the tumor immune microenvironment at early phases of oral cancer development, including the regulation of TA-HEVs in OTSCC.
The role of imprinting genes’ loss of imprints in cancers and their clinical implications
Authors: Xie Guojing , Si Qin , Zhang Guangjie , Fan Yu , Li Qinghua , Leng Ping , Qiao Fengling , Liang Simin , Yu Rong , Wang Yingshuang
Published: May 2024

Genomic imprinting plays an important role in the growth and development of mammals. When the original imprint status of these genes is lost, known as loss of imprinting (LOI), it may affect growth, neurocognitive development, metabolism, and even tumor susceptibility. The LOI of imprint genes has gradually been found not only as an early event in tumorigenesis, but also to be involved in progression. More than 120 imprinted genes had been identified in humans. In this review, we summarized the most studied LOI of two gene clusters and 13 single genes in cancers. We focused on the roles they played, that is, as growth suppressors and anti-apoptosis agents, sustaining proliferative signaling or inducing angiogenesis; the molecular pathways they regulated; and especially their clinical significance. It is notable that 12 combined forms of multi-genes’ LOI, 3 of which have already been used as diagnostic models, achieved good sensitivity, specificity, and accuracy. In addition, the methods used for LOI detection in existing research are classified into detection of biallelic expression (BAE), differentially methylated regions (DMRs), methylation, and single-nucleotide polymorphisms (SNPs). These all indicated that the detection of imprinting genes’ LOI has potential clinical significance in cancer diagnosis, treatment, and prognosis.
The role of miRNAs as biomarkers in breast cancer
Authors: Baylie Temesgen , Kasaw Mulugeta , Getinet Mamaru , Getie Gedefaw , Jemal Mohammed , Nigatu Amare , Ahmed Hassen , Bogale Mihiret
Published: May 2024

Breast cancer (BC) is the second most common cause of deaths reported in women worldwide, and therefore there is a need to identify BC patients at an early stage as timely diagnosis would help in effective management and appropriate monitoring of patients. This will allow for proper patient monitoring and effective care. However, the absence of a particular biomarker for BC early diagnosis and surveillance makes it difficult to accomplish these objectives. miRNAs have been identified as master regulators of the molecular pathways that are emphasized in various tumors and that lead to the advancement of malignancies. Small, non-coding RNA molecules known as miRNAs target particular mRNAs to control the expression of genes. miRNAs dysregulation has been linked to the start and development of a number of human malignancies, including BC, since there is compelling evidence that miRNAs can function as tumor suppressor genes or oncogenes. The current level of knowledge on the role of miRNAs in BC diagnosis, prognosis, and treatment is presented in this review. miRNAs can regulate the tumorigenesis of BC through targeting PI3K pathway and can be used as prognostic or diagnostic biomarkers for BC therapy. Some miRNAs, like miR-9, miR-10b, and miR-17-5p, are becoming known as biomarkers of BC for diagnosis, prognosis, and therapeutic outcome prediction. Other miRNAs, like miR-30c, miR-187, and miR-339-5p, play significant roles in the regulation of hallmark functions of BC, including invasion, metastasis, proliferation, resting death, apoptosis, and genomic instability. Other miRNAs, such as miR-155 and miR-210, are circulating in bodily fluids and are therefore of interest as novel, conveniently accessible, reasonably priced, non-invasive methods for the customized care of patients with BC.
An unusual cause of significantly elevated blood alpha-fetoprotein levels: a case report and literature review
Authors: Zheng Yue , Yao Jianping , Liu Jin , Zhao Feimin
Published: May 2024

Alpha-fetoprotein (AFP) serves as a crucial diagnostic marker for primary hepatocellular carcinoma (HCC) and germ cell tumors (GCTs), with rare instances of significantly elevated levels in other diseases. In this study, we present a case of an elderly patient who was diagnosed with AFP-producing gastric cancer (AFPGC) following an elevated AFP result during physical examination. In investigating liver cancer at an early stage, the diagnosis was missed because of failure in detecting the lesion, resulting in delayed treatment initiation. AFPGC is a rare aggressive tumor that demands heightened awareness among clinicians to foster early detection, diagnosis, and treatment for improved prognosis.
Associations of single and multiple vitamin exposure with childhood eczema: data from the national health and nutrition examination survey
Authors: Wang Fang , Wang Xiaolie , Wang Jiayan , Liu Biqing
Published: May 2024

Aim

The association between vitamins and eczema has garnered attention, yet few studies have evaluated the effects of co-exposure to multiple vitamins on this condition. This study aims to assess the association of vitamin mixtures with eczema in children.

Methods

This cross-sectional study analyzed data from 2,244 children aged 6–17 years from the National Health and Nutrition Examination Surveys. Eczema served as the primary outcome. Six serum vitamins, namely, vitamins A, B6, B12, C, D, and E, were the main variables. Weighted multivariate logistic regression was adopted to analyze the association between each serum vitamin and eczema. Odds ratios (OR) with a 95% confidence interval (CI) were calculated. Bayesian kernel machine regression (BKMR) analysis and the quantile g-computation (qgcomp) model were used to evaluate the association of co-exposure to multiple vitamins with eczema.

Results

In total, 10.83% of children (n = 243) developed eczema. After adjusting for confounding factors, we observed that compared with the reference group (vitamin B12 with second quartile), the OR for eczema was 0.604 (95% CI: 0.373–0.978, P = 0.041) for the first quartile of vitamin B12. Both BKMR analysis and the qgcomp model consistently showed that co-exposure to the six vitamins was positively correlated with the risk of eczema, with vitamin B6 contributing most to the overall effect. In BKMR analyses, we observed an interaction between vitamins B6 and B12 concerning eczema risk.

Conclusion

Co-exposure to vitamins A, C, B6, B12, D, and E was found to be associated with an increased risk of eczema in children, with vitamin B6 as the greatest positive contributor driving the overall effect.
Feature engineering of environmental covariates improves plant genomic-enabled prediction
Authors: Montesinos-López Osval A. , Crespo-Herrera Leonardo , Pierre Carolina Saint , Cano-Paez Bernabe , Huerta-Prado Gloria Isabel , Mosqueda-González Brandon Alejandro , Ramos-Pulido Sofia , Gerard Guillermo , Alnowibet Khalid , Fritsche-Neto Roberto , Montesinos-López Abelardo , Crossa José
Published: May 2024

Introduction

Because Genomic selection (GS) is a predictive methodology, it needs to guarantee high-prediction accuracies for practical implementations. However, since many factors affect the prediction performance of this methodology, its practical implementation still needs to be improved in many breeding programs. For this reason, many strategies have been explored to improve the prediction performance of this methodology.

Methods

When environmental covariates are incorporated as inputs in the genomic prediction models, this information only sometimes helps increase prediction performance. For this reason, this investigation explores the use of feature engineering on the environmental covariates to enhance the prediction performance of genomic prediction models.

Results and discussion

We found that across data sets, feature engineering helps reduce prediction error regarding only the inclusion of the environmental covariates without feature engineering by 761.625% across predictors. These results are very promising regarding the potential of feature engineering to enhance prediction accuracy. However, since a significant gain in prediction accuracy was observed in only some data sets, further research is required to guarantee a robust feature engineering strategy to incorporate the environmental covariates.
Employment equity groups’ experience of inclusion and commitment to the CAF
Authors: Peach Jennifer M. , Laplante Joelle , Boileau Kayla
Published: May 2024

The Canadian Armed Forces (CAF) are subject to the Employment Equity Act, which requires federally regulated employers to identify and eliminate barriers to the employment of designated groups (women, Indigenous peoples, persons with disabilities (PwD), and racialized members), and establish short-term, numerical goals to address underrepresentation. Addressing employment barriers experienced by these equity seeking groups is one of the CAF’s key priorities. The objective of this study is to examine group differences in feelings of inclusion (i.e., relatedness, organizational inclusion, and microaggressions) and retention-related measures (i.e., job satisfaction, affective commitment, and intentions to leave), the contribution of feelings of inclusion to retention measures, and the effect of numerical representation and number of marginalized identities on these concepts. We analyzed data from the 2022 Your Say Matters survey, which was administered to a representative sample of CAF members, with oversampling of under-represented groups. Respondents included 4,483 Regular Force members (30.9% response rate). The groups under study included Indigenous members, persons with disabilities, racialized members, women not part of another group (non-Indigenous, non-racialized, women without disabilities), and everyone else (non-Indigenous, non-racialized, not women, without disabilities). Our hypotheses were supported overall, such that groups with less representation in the CAF scored lower on inclusion measures than groups with more representation. The number of marginalized identities held by military members predicted the inclusion measures, but did not predict retention-related measures. There were some group differences on retention-related measures, such that women not part of another group scored more favorably than other designated groups, and racialized members scored more favorably than PwD and Indigenous members. Inclusion measures predicted job satisfaction, affective commitment, and intentions to leave equally for all groups studied, suggesting that feeling included is important for all.
Leveraging systems science and design thinking to advance implementation science: moving toward a solution-oriented paradigm
Authors: Huang Terry T.-K. , Callahan Emily A. , Haines Emily R. , Hooley Cole , Sorensen Dina M. , Lounsbury David W. , Sabounchi Nasim S. , Hovmand Peter S.
Published: May 2024

Many public health challenges are characterized by complexity that reflects the dynamic systems in which they occur. Such systems involve multiple interdependent factors, actors, and sectors that influence health, and are a primary driver of challenges of insufficient implementation, sustainment, and scale of evidence-based public health interventions. Implementation science frameworks have been developed to help embed evidence-based interventions in diverse settings and identify key factors that facilitate or hinder implementation. These frameworks are largely static in that they do not explain the nature and dynamics of interrelationships among the identified determinants, nor how those determinants might change over time. Furthermore, most implementation science frameworks are top-down, deterministic, and linear, leaving critical gaps in understanding of both how to intervene on determinants of successful implementation and how to scale evidence-based solutions. Design thinking and systems science offer methods for transforming this problem-oriented paradigm into one that is solution-oriented. This article describes these two approaches and how they can be integrated into implementation science strategies to promote implementation, sustainment, and scaling of public health innovation, ultimately resulting in transformative systems changes that improve population health.
Mental health literacy, mental health experiences and help-seeking behaviours of Chinese elite athletes: a qualitative study
Authors: Bu Danran , Zhang Chun-Qing , Liu Jing-Dong , Han Zhe , Wang Xiang , Huang Zhijian
Published: May 2024

Introduction

Elite athletes' help-seeking on mental health might be influenced by their mental health literacy (MHL) and mental health experiences. The current study aimed to explore the MHL, experiences and help-seeking behaviours among elite athletes using a qualitative approach.

Methods

Face-to-face semi-structured interviews were conducted among 20 Chinese elite athletes, 12 coaches, and 5 team officials. Interview data was analyzed using content analysis.

Results

Seven main themes emerged from the analysis. The current study revealed that Chinese elite athletes suffered from various mental health issues and athletes' MHL levels, help-seeking attitudes and intentions, Chinese sports environments, and Chinese cultural background could impact their help-seeking behaviours.

Conclusion

Support for Chinese elite athletes' mental health and help-seeking requires improvement.
A potential pathway for identifying hypertension among urban residents aged 60+ years in China: the role of health insurance
Authors: Dou Yu , Guo Hongmei , Liu Sijun , Xu Huiqing , Li Fengli , Tao Wanying , Jia Shifen , Tian Siyu , Deng Tianrui , Xiong Yaqing , Xu Fei
Published: May 2024

Background

Identification is the first step for treatment of hypertension. However, the awareness rate of hypertension was not high globally. This study aimed to examine the potential role of health insurance for early-identifying hypertension among urban older residents in China.

Methods

In this cross-sectional study, urban residents aged 60+ years were chosen from Nanjing municipality of China in 2018. The outcome measure was hypertension status (“no hypertension,” “diagnosed hypertension” or “un-diagnosed hypertension”). Independent variable was health insurance (“Urban Employee Basic Medical Insurance scheme, UEBMI” or “Urban Resident Basic Medical Insurance scheme, URBMI”). Logistic regression models were introduced to estimate odds ratio (OR) and 95% confidence interval (CI) to examine the association between health insurance and hypertension.

Results

Totally, 19,742 participants completed the study. Among overall, URBMI and UEBMI participants, 47.2% (95%CI = 46.5, 47.9%), 38.4% (95%CI = 37.3, 39.6%) and 52.1% (95%CI = 51.2, 53.0%), separately, were diagnosed with hypertension, while the prevalence of un-diagnosed hypertension was 12.7% (95%CI = 12.2, 13.2%), 18.5% (95%CI = 17.6, 19.4%) and 9.6% (95%CI = 9.1, 10.1%), respectively. For overall participants, those with UEBMI were more likely to have hypertension identified (OR = 1.20; 95%CI = 1.11, 1.29) and at lower odds to experience un-diagnosed hypertension (OR = 0.68; 95%CI = 0.61, 0.76) compared to their counterparts with URBMI after control for potential confounders. Moreover, such associations of health insurance with diagnosed and un-diagnosed hypertension were also observed among participants stratified by age and gender.

Conclusion

Favorable health insurance may be a pathway for identifying hypertension among urban older residents in China. This study has important public health implications that hypertension may be identified early through favorable health insurance policies for older residents in China.
Guiding organs-on-chips towards applications: a balancing act between integration of advanced technologies and standardization
Authors: Meneses J. , Conceição F. , van der Meer A. D. , de Wit S. , Moreira Teixeira L.
Published: May 2024

Organs-on-chips (OoC) are in vitro models that emulate key functionalities of tissues or organs in a miniaturized and highly controlled manner. Due to their high versatility, OoC have evolved as promising alternatives to animal testing for a more effective drug development pipeline. Additionally, OoC are revealing increased predictive power for toxicity screening applications as well as (patho-) physiology research models. It is anticipated that enabling technologies such as biofabrication, multimodality imaging, and artificial intelligence will play a critical role in the development of the next generation of OoC. These domains are expected to increase the mimicry of the human micro-physiology and functionality, enhance screening of cellular events, and generate high-content data for improved prediction. Although exponentially growing, the OoC field will strongly benefit from standardized tools to upgrade its implementational power. The complexity derived from the integration of multiple technologies and the current absence of concrete guidelines for establishing standards may be the reason for the slower adoption of OoC by industry, despite the fast progress of the field. Therefore, we argue that it is essential to consider standardization early on when using new enabling technologies, and we provide examples to illustrate how to maintain a focus on technology standards as these new technologies are used to build innovative OoC applications. Moreover, we stress the importance of informed design, use, and analysis decisions. Finally, we argue that this early focus on standards in innovation for OoC will facilitate their implementation.
Innovative development of small resort towns: the triad of science, business, and education
Authors: Ressin Marat
Published: May 2024

Urban areas are places associated with the transformation of ideas into practices, social initiatives, and spatial economics. The study aims to assess the triad interaction between education, science, and business as a multiplier on the socio-economic development in the region. The study built a conceptual model of socio-economic space in the context of innovative urban development: the unity of education, science, and business. The statistical analysis allowed the author to substantiate the peculiarities of the local triad. The study revealed correlations in the influence of education, science, and business on changes in the regional system. The paper suggests that the triad of education, science, and business rests on territorial specifics. This feature is the determining factor of innovative development in the field of resort towns. The presented research uses the quantitatively measured influence of the triad as a multiplier by combining values of the unity of education, science, and business. The study found that the mentioned indicator reflects the wellbeing and quality of the labor resources in the region. On the one hand, the multiplicative influence of the triad is a guarantee of an increase in the wellbeing level within the borders of the region. On the other hand, it requires adaptation of the innovative development of resort towns to the current growth of the workforce and a decrease in innovative advantages on a local scale. The findings provide policymakers with significant indicators on the way to stabilizing the regional economy and effective decision-making. The study of the interaction between education, science, and business in the context of socioeconomic development can become a crucial tool for formulating policies aimed at stabilizing the region's economy and improving the quality of life of its residents, particularly in resort cities. The obtained results can provide guidelines for the development of innovation support programs and the planning of investment strategies, taking into account the specifics of territorial conditions.
An ethnography of construction and characteristics of curriculum for inheritance of intangible cultural heritage martial arts in universities
Authors: Cheng Yuanlong , Guo Nana
Published: May 2024

Background

Inheriting excellent traditional Chinese culture is a prerequisite for ensuring the continuity of the cultural genes of the Chinese nation. However, with the historical mission of shaping the national character of the descendants of the Chinese nation, intangible cultural heritage martial arts face the problem of an unclear curriculum content construction mechanism in university inheritance and make it difficult for these martial arts to shoulder the responsibility of cultural inheritance in the era.

Method

Educational ethnography as a research method is conducive to the in-depth exploration of the mechanism of curriculum content construction in the inheritance of intangible cultural heritage martial arts in universities.

Results

Research suggests that the construction of curriculum content for the inheritance of intangible cultural heritage martial arts in universities relies on the form of cooperation between universities and inheritors, and form three models of curriculum content construction: off campus, on campus, and on-campus cooperation. The construction of curriculum content for off-campus inheritors belongs to the “attachment style” model, which is based on the actual needs of the inheritors and the selection of boxing types. The construction of curriculum content for inheritors on campus belongs to the “reshaping” model, which is the inheritor's “simplification and reorganization” based on traditional routines and subjective and objective conditions of inheritance. The construction of course content in school local cooperation belongs to the “integrated” model, which is the reintegration of course content by universities based on their own development characteristics and the characteristics of various martial arts.

Conclusion

In the inheritance of intangible cultural heritage martial arts in universities, emphasis is placed on local knowledge, core skills, cultural traditions, and other characteristics, highlighting the excellence of its cultural inheritance. In the future, the focus of the inheritance of these martial arts in universities should be to cultivate innovative talents who are familiar with both traditional and modern martial arts.