bluuebunny/crossref_metadata_2025 huggingface dataset:
Is the MIND diet useful for polycystic ovary syndrome? A case-control study
Authors: Darand Mina , Sadeghi Narges , Salimi Zahra , Nikbaf-Shandiz Mahlagha , Panjeshahin Asieh , Fateh Hawal Lateef , Hosseinzadeh Mahdieh
Published: May 2024

Background

Polycystic ovary syndrome (PCOS) is the most prevalent cause of ovulatory infertility and endocrine abnormalities in reproductive-age women. Although the MIND diet has been introduced to improve brain function, evidence shows that the MIND diet is rich in beneficial food groups that can have a preventive effect on other metabolic disorders. The present study was conducted to investigate the association between adherence to the MIND diet and PCOS.

Methods

This age and BMI frequency-matched case-control study was conducted on 216 women between January 2018 and March 2019 in Yazd, Iran. PCOS was diagnosed based on Rotterdam criteria. Participants were selected by convenience sampling method. The validated 178-item food frequency questionnaire was used to assess the usual dietary intake. Logistic regression was used to estimate the association between the MIND diet and PCOS.

Results

The findings of the present study showed a significant inverse association between adherence to the MIND diet and PCOS in the crude model (OR for T3 vs. T1: 0.12 (95% CI: 0.05–0.25), P-value < 0.001) and multivariable-adjusted model including energy intake, age, BMI, waist circumference, marital status, pregnancy history, drug use history, education and physical activity (OR for T3 vs. T1 = 0.08 (95% CI: 0.03–0.19), P-value < 0.001). Adherence to the MIND diet had a protective effect of 92%.

Conclusion

Although the results of the present study showed that higher adherence to the MIND diet is associated with a lower risk of PCOS, more studies are needed to confirm these findings in the future.
Is patients’ activities of daily living self-care score in Norwegian home care a proxy for workers standing at work?
Authors: Lohne Fredrik Klæboe , Fimland Marius Steiro , Rasmussen Charlotte Lund , Liaset Ingeborg Frostad , Fischer Heike , Redzovic Skender
Published: May 2024

Background

Prolonged standing at work may contribute to increased risk of musculoskeletal pain in home care workers. Patients’ activities of daily living (ADL) score may be a proxy for home care workers’ standing time at work. The objective of the present study was to investigate the association between patients’ ADL self-care score, and workers standing time.

Methods

This cross-sectional study measured time spent standing, sitting and in physical activity for seven days using thigh-worn accelerometers, among 14 home care workers. Patients’ ADL self-care scores are routinely adjusted by home care nurses, and time intervals of home care visits are stored in home care services electronic patient journal. We collected ADL self-care scores and start and end time points of visits, and categorized ADL self-care scores as low (ADL ≤ 2.0), medium (ADL > 2.0 to 3.0) or high (ADL > 3.0). Physical behavior data were transformed to isometric log-ratios and a mixed-effect model was used to investigate differences in physical behavior between the three ADL self-care score categories.

Results

We analyzed 931 patient visits and found that high ADL self-care scores were associated with longer standing times relative to sitting and physical activity, compared to low ADL score (0.457, p = 0.001). However, no significant differences in time spent standing were found between high and medium ADL patient visits (0.259, p = 0.260), nor medium and low (0.204, p = 0.288). High ADL score patients made up 33.4% of the total care time, despite only making up 7.8% of the number of patients.

Conclusion

Our findings suggest that caring for patients with high ADL self-care score requires workers to stand for longer durations and that this group of patients constitute a significant proportion of home care workers’ total work time. The findings of this study can inform interventions to improve musculoskeletal health among home care workers by appropriate planning of patient visits.
Getting an outsider’s perspective - sick-listed workers’ experiences with early follow-up sessions in the return to work process: a qualitative interview study
Authors: Standal Martin Inge , Foldal Vegard Stolsmo , Aasdahl Lene , Fors Egil A. , Solbjør Marit
Published: May 2024

Purpose

The aim of this study was to explore how early follow-up sessions (after 14 and 16 weeks of sick leave) with social insurance caseworkers was experienced by sick-listed workers, and how these sessions influenced their return-to-work process.

Methods

A qualitative interview study with sick-listed workers who completed two early follow-up sessions with caseworkers from the Norwegian Labor and Welfare Administration (NAV). Twenty-six individuals aged 30 to 60 years with a sick leave status of 50–100% participated in semi-structured interviews. The data was analyzed with thematic analysis.

Results

Participants’ experiences of the early follow-up sessions could be categorized into three themes: (1) Getting an outsider’s perspective, (2) enhanced understanding of the framework for long term sick-leave, and (3) the empathic and personal face of the social insurance system. Meeting a caseworker enabled an outsider perspective that promoted critical reflection and calibration of their thoughts. This was experienced as a useful addition to the support many received from their informal network, such as friends, family, and co-workers. The meetings also enabled a greater understanding of their rights and duties, possibilities, and limitations regarding welfare benefits, while also displaying an unexpected empathic and understanding perspective from those working in the social insurance system.

Conclusion

For sick-listed individuals, receiving an early follow-up session from social insurance caseworkers was a positive experience that enhanced their understanding of their situation, and promoted reflection towards RTW. Thus, from the perspective of the sick-listed workers, early sessions with social insurance caseworkers could be a useful addition to the overall sickness absence follow-up.
Exploiting urine-derived induced pluripotent stem cells for advancing precision medicine in cell therapy, disease modeling, and drug testing
Authors: Yin Xiya , Li Qingfeng , Shu Yan , Wang Hongbing , Thomas Biju , Maxwell Joshua T. , Zhang Yuanyuan
Published: May 2024

The field of regenerative medicine has witnessed remarkable advancements with the emergence of induced pluripotent stem cells (iPSCs) derived from a variety of sources. Among these, urine-derived induced pluripotent stem cells (u-iPSCs) have garnered substantial attention due to their non-invasive and patient-friendly acquisition method. This review manuscript delves into the potential and application of u-iPSCs in advancing precision medicine, particularly in the realms of drug testing, disease modeling, and cell therapy. U-iPSCs are generated through the reprogramming of somatic cells found in urine samples, offering a unique and renewable source of patient-specific pluripotent cells. Their utility in drug testing has revolutionized the pharmaceutical industry by providing personalized platforms for drug screening, toxicity assessment, and efficacy evaluation. The availability of u-iPSCs with diverse genetic backgrounds facilitates the development of tailored therapeutic approaches, minimizing adverse effects and optimizing treatment outcomes. Furthermore, u-iPSCs have demonstrated remarkable efficacy in disease modeling, allowing researchers to recapitulate patient-specific pathologies in vitro. This not only enhances our understanding of disease mechanisms but also serves as a valuable tool for drug discovery and development. In addition, u-iPSC-based disease models offer a platform for studying rare and genetically complex diseases, often underserved by traditional research methods. The versatility of u-iPSCs extends to cell therapy applications, where they hold immense promise for regenerative medicine. Their potential to differentiate into various cell types, including neurons, cardiomyocytes, and hepatocytes, enables the development of patient-specific cell replacement therapies. This personalized approach can revolutionize the treatment of degenerative diseases, organ failure, and tissue damage by minimizing immune rejection and optimizing therapeutic outcomes. However, several challenges and considerations, such as standardization of reprogramming protocols, genomic stability, and scalability, must be addressed to fully exploit u-iPSCs’ potential in precision medicine. In conclusion, this review underscores the transformative impact of u-iPSCs on advancing precision medicine and highlights the future prospects and challenges in harnessing this innovative technology for improved healthcare outcomes.
Targeting cathepsin S promotes activation of OLF1-BDNF/TrkB axis to enhance cognitive function
Authors: Lee Hao-Wei , Chen Szu-Jung , Tsai Kuen-Jer , Hsu Kuei-Sen , Chen Yi-Fan , Chang Chih-Hua , Lin Hsiao-Han , Hsueh Wen-Yun , Hsieh Hsing-Pang , Lee Yueh-Feng , Chiang Huai-Chueh , Chang Jang-Yang
Published: May 2024

Background

Cathepsin S (CTSS) is a cysteine protease that played diverse roles in immunity, tumor metastasis, aging and other pathological alterations. At the cellular level, increased CTSS levels have been associated with the secretion of pro-inflammatory cytokines and disrupted the homeostasis of Ca2+ flux. Once CTSS was suppressed, elevated levels of anti-inflammatory cytokines and changes of Ca2+ influx were observed. These findings have inspired us to explore the potential role of CTSS on cognitive functions.

Methods

We conducted classic Y-maze and Barnes Maze tests to assess the spatial and working memory of Ctss−/− mice, Ctss+/+ mice and Ctss+/+ mice injected with the CTSS inhibitor (RJW-58). Ex vivo analyses including long-term potentiation (LTP), Golgi staining, immunofluorescence staining of sectioned whole brain tissues obtained from experimental animals were conducted. Furthermore, molecular studies were carried out using cultured HT-22 cell line and primary cortical neurons that treated with RJW-58 to comprehensively assess the gene and protein expressions.

Results

Our findings reported that targeting cathepsin S (CTSS) yields improvements in cognitive function, enhancing both working and spatial memory in behavior models. Ex vivo studies showed elevated levels of long-term potentiation levels and increased synaptic complexity. Microarray analysis demonstrated that brain-derived neurotrophic factor (BDNF) was upregulated when CTSS was knocked down by using siRNA. Moreover, the pharmacological blockade of the CTSS enzymatic activity promoted BDNF expression in a dose- and time-dependent manner. Notably, the inhibition of CTSS was associated with increased neurogenesis in the murine dentate gyrus. These results suggested a promising role of CTSS modulation in cognitive enhancement and neurogenesis.

Conclusion

Our findings suggest a critical role of CTSS in the regulation of cognitive function by modulating the Ca2+ influx, leading to enhanced activation of the BDNF/TrkB axis. Our study may provide a novel strategy for improving cognitive function by targeting CTSS.
Feasibility of restricting e-cigarettes to prescription only for smoking cessation
Authors: Peri Katya , Eisenberg Mark J.
Published: May 2024

E-cigarette use among youth in Canada has risen to epidemic proportions. E-cigarettes are also moderately useful smoking cessations aids. Restricting e-cigarettes to prescription only smoking cessation aids could help limit youth’s access to them while keeping them available as therapies for patients who smoke conventional cigarettes. In Canada, drugs or devices must be approved by regulatory bodies such as Health Canada in order to become licensed prescription medications. A similar situation is underway in Australia, where e-cigarettes have been restricted to prescription only. This commentary explores the feasibility of a similar regulation for e-cigarettes in Canada as prescription smoking cessation aids.
GDF15 ameliorates sepsis-induced lung injury via AMPK-mediated inhibition of glycolysis in alveolar macrophage
Authors: Lu Shasha , Li Ranran , Deng Yunxin , Bai Ju , Ji Bangqi , Chu Yufeng , Xu Yan , Qu Hongping , Guo Xiaosun , Li Pibao , Meng Mei
Published: May 2024

Growth differentiation factor 15 (GDF15) as a stress response cytokine is involved in the development and progression of several diseases associated with metabolic disorders. However, the regulatory role and the underlying mechanisms of GDF15 in sepsis remain poorly defined. Our study analyzed the levels of GDF15 and its correlations with the clinical prognosis of patients with sepsis. In vivo and in vitro models of sepsis were applied to elucidate the role and mechanisms of GDF15 in sepsis-associated lung injury. We observed strong correlations of plasma GDF15 levels with the levels of C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), and lactate as well as Sequential Organ Failure Assessment (SOFA) scores in patients with sepsis. In the mouse model of lipopolysaccharide-induced sepsis, recombinant GDF15 inhibited the proinflammatory responses and alleviated lung tissue injury. In addition, GDF15 decreased the levels of cytokines produced by alveolar macrophages (AMs). The anti-inflammatory effect of glycolysis inhibitor 2-DG on AMs during sepsis was mediated by GDF15 via inducing the phosphorylation of the α-subunit of eukaryotic initiation factor 2 (eIF2α) and the expression of activating transcription factor 4 (ATF4). Furthermore, we explored the mechanism underlying the beneficial effects of GDF15 and found that GDF15 inhibited glycolysis and mitogen-activated protein kinases (MAPK)/nuclear factor-κB (NF-κB) signaling via promoting AMPK phosphorylation. This study demonstrated that GDF15 inhibited glycolysis and NF-κB/MAPKs signaling via activating AMP-activated protein kinase (AMPK), thereby alleviating the inflammatory responses of AMs and sepsis-associated lung injury. Our findings provided new insights into novel therapeutic strategies for treating sepsis.
Association between the stress hyperglycemia ratio and 28-day all-cause mortality in critically ill patients with sepsis: a retrospective cohort study and predictive model establishment based on machine learning
Authors: Yan Fengjuan , Chen Xiehui , Quan Xiaoqing , Wang Lili , Wei Xinyi , Zhu Jialiang
Published: May 2024

Background

Sepsis is a severe form of systemic inflammatory response syndrome that is caused by infection. Sepsis is characterized by a marked state of stress, which manifests as nonspecific physiological and metabolic changes in response to the disease. Previous studies have indicated that the stress hyperglycemia ratio (SHR) can serve as a reliable predictor of adverse outcomes in various cardiovascular and cerebrovascular diseases. However, there is limited research on the relationship between the SHR and adverse outcomes in patients with infectious diseases, particularly in critically ill patients with sepsis. Therefore, this study aimed to explore the association between the SHR and adverse outcomes in critically ill patients with sepsis.

Methods

Clinical data from 2312 critically ill patients with sepsis were extracted from the MIMIC-IV (2.2) database. Based on the quartiles of the SHR, the study population was divided into four groups. The primary outcome was 28-day all-cause mortality, and the secondary outcome was in-hospital mortality. The relationship between the SHR and adverse outcomes was explored using restricted cubic splines, Cox proportional hazard regression, and Kaplan‒Meier curves. The predictive ability of the SHR was assessed using the Boruta algorithm, and a prediction model was established using machine learning algorithms.

Results

Data from 2312 patients who were diagnosed with sepsis were analyzed. Restricted cubic splines demonstrated a "U-shaped" association between the SHR and survival rate, indicating that an increase in the SHR is related to an increased risk of adverse events. A higher SHR was significantly associated with an increased risk of 28-day mortality and in-hospital mortality in patients with sepsis (HR > 1, P < 0.05) compared to a lower SHR. Boruta feature selection showed that SHR had a higher Z score, and the model built using the rsf algorithm showed the best performance (AUC = 0.8322).

Conclusion

The SHR exhibited a U-shaped relationship with 28-day all-cause mortality and in-hospital mortality in critically ill patients with sepsis. A high SHR is significantly correlated with an increased risk of adverse events, thus indicating that is a potential predictor of adverse outcomes in patients with sepsis.
Reversing the directionality of reactions between non-oxidative pentose phosphate pathway and glycolytic pathway boosts mycosporine-like amino acid production in Saccharomyces cerevisiae
Authors: Hengardi Miselle Tiana , Liang Cui , Madivannan Keshiniy , Yang Lay Kien , Koduru Lokanand , Kanagasundaram Yoganathan , Arumugam Prakash
Published: May 2024

Background

Mycosporine-like amino acids (MAAs) are a class of strongly UV-absorbing compounds produced by cyanobacteria, algae and corals and are promising candidates for natural sunscreen components. Low MAA yields from natural sources, coupled with difficulties in culturing its native producers, have catalyzed synthetic biology-guided approaches to produce MAAs in tractable microbial hosts like Escherichia coli, Saccharomyces cerevisiae and Corynebacterium glutamicum. However, the MAA titres obtained in these hosts are still low, necessitating a thorough understanding of cellular factors regulating MAA production.

Results

To delineate factors that regulate MAA production, we constructed a shinorine (mycosporine-glycine-serine) producing yeast strain by expressing the four MAA biosynthetic enzymes from Nostoc punctiforme in Saccharomyces cerevisiae. We show that shinorine is produced from the pentose phosphate pathway intermediate sedoheptulose 7-phosphate (S7P), and not from the shikimate pathway intermediate 3-dehydroquinate (3DHQ) as previously suggested. Deletions of transaldolase (TAL1) and phosphofructokinase (PFK1/PFK2) genes boosted S7P/shinorine production via independent mechanisms. Unexpectedly, the enhanced S7P/shinorine production in the PFK mutants was not entirely due to increased flux towards the pentose phosphate pathway. We provide multiple lines of evidence in support of a reversed pathway between glycolysis and the non-oxidative pentose phosphate pathway (NOPPP) that boosts S7P/shinorine production in the phosphofructokinase mutant cells.

Conclusion

Reversing the direction of flux between glycolysis and the NOPPP offers a novel metabolic engineering strategy in Saccharomyces cerevisiae.
The m6A reader IGF2BP2 promotes esophageal cell carcinoma progression by enhancing EIF4A1 translation
Authors: Li Yuan , Xiao Zhuya , Wang Yingying , Zhang Daoming , Chen Zuhua
Published: May 2024

Esophageal squamous cell carcinoma (ESCC) is one of most prevalent cancers worldwide, especially in China. Lacking in depth mechanism study, effective targets and therapeutics are desperately needed in the clinic. RNA-binding proteins (RBPs) mediate the localization, stability, and translation of the target transcripts and fine-tune the physiological functions of the proteins encoded. Bioinformatics analysis revealed that IGF2BPs were highly expressed in ESCC tissues and at least participated in the regulation of cell proliferation of ESCC cells. Biological researches demonstrated that IGF2BP2 promoted the cell proliferation, migration and invasion of ESCC KYSE30 and KYSE450 cells. IGF2BP2 could bind to EIF4A1 mRNA by recognition of m6A sites and enhanced translation of EIF4A1. IGF2BPs, as m6A reader, IGF2BPs were oncogenic genes in ESCC by regulating the expression of EIF4A1 through m6A sites. IGF2BP2, EIF4A1 and their targets could serve as potential biomarkers and therapeutic targets for ESCC, offering promising novel approaches for the diagnosis and treatment of ESCC.
PD-L1 intrinsically promotes the proliferation of breast cancer cells through the SKP2-p27/p21 axis
Authors: Elfoly Marwa , Mirza Jumanah Y. , Alaiya Ayodele , Al-Hazzani Amal A. , Tulbah Asma , Al-Alwan Monther , Ghebeh Hazem
Published: May 2024

Background

PD-L1 intrinsically promotes tumor progression through multiple mechanisms, which potentially leads to resistance to anti-PD-1/PD-L1 therapies. The intrinsic effect of PD-L1 on breast cancer (BC) cell proliferation has not been fully elucidated.

Methods

we used proteomics, gene expression knockdown (KD), quantitative immunofluorescence (qIF), western blots, functional assays including colony-forming assay (CFA) and real-time cell analyzer (RTCA), and in vivo data using immunohistochemistry in breast cancer patients.

Results

PD-L1 promoted BC cell proliferation by accelerating cell cycle entry at the G1-to-S phase transition. Global proteomic analysis of the differentially expressed nuclear proteins indicated the involvement of several proliferation-related molecules, including p21CIP1/WAF1. Western blotting and qIF demonstrated the higher expression of SKP2 and the lower expression of p21CIP1/WAF1 and p27Kip1 in PD-L1 expressing (PD-L1pos) cells as compared to PD-L1 KD (PD-L1KD) cells. Xenograft-derived cells and the TCGA BC dataset confirmed this relationship in vivo. Functionally, CFA and RTCA demonstrated the central role of SKP2 in promoting PD-L1-mediated proliferation. Finally, immunohistochemistry in 74 breast cancer patients confirmed PD-L1 and SKP-p21/p27 axis relationship, as it showed a highly statistically significant correlation between SKP2 and PD-L1 expression (p < 0.001), and both correlated significantly with the proliferation marker Ki-67 (p < 0.001). On the other hand, there was a statistically significant inverse relationship between PD-L1 and p21CIP1/WAF1 expression (p = 0.005). Importantly, double negativity for p21CIP1/WAF1 and p27Kip1 correlated significantly with PD-L1 (p < 0.001), SKP2 (p = 0.002), and Ki-67 (p = 0.002).

Conclusions

we have demonstrated the role of the SKP2-p27/p21 axis in intrinsic PD-L1-enhanced cell cycle progression. Inhibitors of SKP2 expression can alleviate resistance to ICPIs.
Kinetics of glucose-6-phosphate dehydrogenase (G6PD) activity during Plasmodium vivax infection: implications for early radical malaria treatment
Authors: Dahuron Laureen , Goungounga Juste , Drame Moustapha , Douine Maylis , Nacher Mathieu , Blaise Théo , Mosnier Emilie , Musset Lise , Fouillet Marie , Djossou Félix , Epelboin Loïc
Published: May 2024

Background

Plasmodium vivax relapses due to dormant liver hypnozoites can be prevented with primaquine. However, the dose must be adjusted in individuals with glucose-6-phosphate-dehydrogenase (G6PD) deficiency. In French Guiana, assessment of G6PD activity is typically delayed until day (D)14 to avoid the risk if misclassification. This study assessed the kinetics of G6PD activity throughout P. vivax infection to inform the timing of treatment.

Methods

For this retrospective monocentric study, data on G6PD activity between D1 and D28 after treatment initiation with chloroquine or artemisinin-based combination therapy were collected for patients followed at Cayenne Hospital, French Guiana, between January 2018 and December 2020. Patients were divided into three groups based on the number of available G6PD activity assessments: (i) at least two measurements during the P. vivax malaria infection; (ii) two measurements: one during the current infection and one previously; (iii) only one measurement during the malaria infection.

Results

In total, 210 patients were included (80, 20 and 110 in groups 1, 2 and 3, respectively). Data from group 1 showed that G6PD activity remained stable in each patient over time (D1, D3, D7, D14, D21, D28). None of the patients with normal G6PD activity during the initial phase (D1–D3) of the malaria episode (n = 44) was categorized as G6PD-deficient at D14. Patients with G6PD activity < 80% at D1 or D3 showed normal activity at D14. Sex and reticulocyte count were statistically associated with G6PD activity variation. In the whole sample (n = 210), no patient had severe G6PD deficiency (< 10%) and only three between 10 and 30%, giving a G6PD deficiency prevalence of 1.4%. Among the 100 patients from group 1 and 2, 30 patients (26.5%) were lost to follow-up before primaquine initiation.

Conclusions

In patients treated for P. vivax infection, G6PD activity did not vary over time. Therefore, G6PD activity on D1 instead of D14 could be used for primaquine dose-adjustment. This could allow earlier radical treatment with primaquine, that could have a public health impact by decreasing early recurrences and patients lost to follow-up before primaquine initiation. This hypothesis needs to be confirmed in larger prospective studies.
Radiotherapy-sensitized cancer immunotherapy via cGAS-STING immune pathway by activatable nanocascade reaction
Authors: Hu Honglei , Zheng Shuting , He Chenxi , Zheng Yinfei , Wei Qiming , Chen Siwen , Wu Zede , Xu Yikai , Zhao Bingxia , Yan Chenggong
Published: May 2024

Radiotherapy-induced immune activation holds great promise for optimizing cancer treatment efficacy. Here, we describe a clinically used radiosensitizer hafnium oxide (HfO2) that was core coated with a MnO2 shell followed by a glucose oxidase (GOx) doping nanoplatform (HfO2@MnO2@GOx, HMG) to trigger ferroptosis adjuvant effects by glutathione depletion and reactive oxygen species production. This ferroptosis cascade potentiation further sensitized radiotherapy by enhancing DNA damage in 4T1 breast cancer tumor cells. The combination of HMG nanoparticles and radiotherapy effectively activated the damaged DNA and Mn2+-mediated cGAS-STING immune pathway in vitro and in vivo. This process had significant inhibitory effects on cancer progression and initiating an anticancer systemic immune response to prevent distant tumor recurrence and achieve long-lasting tumor suppression of both primary and distant tumors. Furthermore, the as-prepared HMG nanoparticles “turned on” spectral computed tomography (CT)/magnetic resonance dual-modality imaging signals, and demonstrated favorable contrast enhancement capabilities activated by under the GSH tumor microenvironment. This result highlighted the potential of nanoparticles as a theranostic nanoplatform for achieving molecular imaging guided tumor radiotherapy sensitization induced by synergistic immunotherapy.
Association between pathologic complete response and biochemical indicators after neoadjuvant therapy for HER2-positive breast cancer
Authors: Chen Wei , Zhang Jing , Li Fenxiang , Chen Zongshun , Li Junjie , Lu Da-Lin
Published: May 2024

Purpose

This study investigated the changes in the fasting blood glucose (FBG), fasting triglyceride (FTG), and fasting total cholesterol (FTC) levels during neoadjuvant therapy (NAT) for human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) and the association with pathologic complete response (pCR).

Methods

Relevant data from Sichuan Cancer Hospital from June 2019 to June 2022 were collected and analyzed, and FBG, FTG, and FTC were divided into baseline, change, and process groups, which were grouped to analyze the changes after receiving NAT and the association with pCR.

Results

In the estrogen receptor (ER)-negative subgroup, patients with low levels of FTG in the process group were more likely to achieve pCR compared to high levels, and in the progesterone receptor (PR)-negative subgroup, patients with lower FTG compared to higher FTG after receiving NAT was more likely to achieve pCR.

Conclusions

Patients with HER2-positive BC undergoing NAT develop varying degrees of abnormalities (elevated or decreased) in FBG, FTG, and FTC; moreover, the status of FTG levels during NAT may predict pCR in ER-negative or PR-negative HER2-positive BC.Early monitoring and timely intervention for FTG abnormalities may enable this subset of patients to increase the likelihood of obtaining a pCR along with management of abnormal markers.
A case of mistaken identity: a systematic review, meta-analysis, and reinvestigation of hemotropic Mycoplasma spp. infection in Ctenocephalides felis (cat flea)
Authors: Moore Charlotte O. , Lashnits Erin , Lappin Michael , Hawley Jennifer , Breitschwerdt Edward B.
Published: May 2024

Background

Feline-associated hemotropic Mycoplasma (hemoplasmas) are believed to be transmitted by two primary mechanisms: (1) direct transmission via fighting and (2) vector-borne transmission by the cat flea (Ctenocephalides felis). While the efficiency of transmission by C. felis appears low, most manuscripts focus on the prevalence of hemoplasmas in wild-caught fleas and report either a very low (< 3%) or a high (> 26%) prevalence. Therefore, we aimed to assess the influence of sample processing and PCR methods on C. felis hemoplasma infection prevalence.

Methods

A systemic review of PubMed articles identified 13 manuscripts (1,531 fleas/flea pools) that met the inclusion criteria (performed PCR for >1 hemoplasma on C. felis collected from cats). Risk of bias was assessed utilizing the ROBINS-E tool. Meta-analysis performed in R of these manuscripts found that not washing samples and a common set of 16S rRNA primers first published in Jensen et al. 2001 were associated with increased hemoplasma prevalence. To evaluate the influence of washing on newly collected fleas, we assessed the hemoplasma status of 20 pools of 5 C. felis each, half of which were washed and half not washed.

Results

Flea washing did not influence the detection of hemoplasma but instead amplified Spiroplasma. To assess non-specific amplification with the Jensen et al. 2001 primers, 67 C. felis samples (34% previously reported hemoplasma infected) were subject to PCR and sequencing. By this method, hemoplasma was detected in only 3% of samples. In the remaining “hemoplasma infected” fleas, PCR amplified Spiroplasma or other bacteria.

Conclusions

Therefore, we concluded that hemoplasma infection in C. felis is rare, and future flea prevalence studies should sequence all positive amplicons to validate PCR specificity. Further investigation of alternative methods of feline-associated hemoplasma transmission and the ability of C. felis to maintain hemoplasma infection is necessary.

Graphical Abstract
Sub-microscopic Plasmodium falciparum infections and multiple drug resistant single nucleotide polymorphic alleles in pregnant women from southwestern Nigeria
Authors: Ibekpobaoku Agatha N. , Oboh Mary A. , Faal Fatou , Adeniji Elizabeth , Ajibaye Olusola , Idowu Emmanuel T. , Amambua-Ngwa Alfred
Published: May 2024

Objectives

The study evaluated sub-microscopic malaria infections in pregnancy using two malaria Rapid Diagnostic Tests (mRDTs), microscopy and RT-PCR and characterized Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and Plasmodium falciparum dihydropteroate synthase (Pfdhps) drug resistant markers in positive samples.

Methods

This was a cross sectional survey of 121 pregnant women. Participants were finger pricked, blood drops were collected for rapid diagnosis with P. falciparum histidine-rich protein 11 rapid diagnostic test kit and the ultra-sensitive Alere Pf malaria RDT, Blood smears for microscopy and dried blood spots on Whatman filter paper for molecular analysis were made. Real time PCR targeting the var acidic terminal sequence (varATS) gene of P. falciparum was carried out on a CFX 96 real time system thermocycler (BioRad) in discriminating malaria infections. For each run, laboratory strain of P. falciparum 3D7 and nuclease free water were used as positive and negative controls respectively. Additionally, High resolution melt analyses was employed for genotyping of the different drug resistance markers.

Results

Out of one hundred and twenty-one pregnant women sampled, the SD Bioline™ Malaria Ag P.f HRP2-based malaria rapid diagnostic test (mRDT) detected eight (0.06%) cases, the ultra-sensitive Alere™ malaria Ag P.f rapid diagnostic test mRDT had similar outcome in the same samples as detected by the HRP2-based mRDT. Microscopy and RT-PCR confirmed four out of the eight infections detected by both rapid diagnostic tests as true positive and RT-PCR further detected three false negative samples by the two mRDTs providing a sub-microscopic malaria prevalence of 3.3%. Single nucleotide polymorphism in Pfdhps gene associated with sulphadoxine resistance revealed the presence of S613 mutant genotypes in three of the seven positive isolates and isolates with mixed wild/mutant genotype at codon A613S. Furthermore, four mixed genotypes at the A581G codon were also recorded while the other Pfdhps codons (A436G, A437G and K540E) showed the presence of wild type alleles. In the Pfdhfr gene, there were mutations in 28.6%, 28.6%, and 85.7% at the I51, R59 and N108 codons respectively. Mixed wild and mutant type genotypes were also observed in 28.6% each of the N51I, and C59R codons. For the Pfcrt, two haplotypes CVMNK and CVIET were observed. The SVMNT was altogether absent. Triple mutant CVIET 1(14.3%) and triple mutant + wild genotype CVIET + CVMNK 1(14.3%) were observed. The Pfmdr1 haplotypes were single mutants YYND 1(14.3%); NFND 1(14.3%) and double mutants YFND 4(57.1%); YYDD 1(14.3%).
Unveiling the role of CaMKII in retinal degeneration: from biological mechanism to therapeutic strategies
Authors: Sun Yuxin , Hao Mengyu , Wu Hao , Zhang Chengzhi , Wei Dong , Li Siyu , Song Zongming , Tao Ye
Published: May 2024

Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a family of broad substrate specificity serine (Ser)/threonine (Thr) protein kinases that play a crucial role in the Ca2+-dependent signaling pathways. Its significance as an intracellular Ca2+ sensor has garnered abundant research interest in the domain of neurodegeneration. Accumulating evidences suggest that CaMKII is implicated in the pathology of degenerative retinopathies such as diabetic retinopathy (DR), age-related macular degeneration (AMD), retinitis pigmentosa (RP) and glaucoma optic neuropathy. CaMKII can induce the aberrant proliferation of retinal blood vessels, influence the synaptic signaling, and exert dual effects on the survival of retinal ganglion cells and pigment epithelial cells. Researchers have put forth multiple therapeutic agents, encompassing small molecules, peptides, and nucleotides that possess the capability to modulate CaMKII activity. Due to its broad range isoforms and splice variants therapeutic strategies seek to inhibit specifically the CaMKII are confronted with considerable challenges. Therefore, it becomes crucial to discern the detrimental and advantageous aspects of CaMKII, thereby facilitating the development of efficacious treatment. In this review, we summarize recent research findings on the cellular and molecular biology of CaMKII, with special emphasis on its metabolic and regulatory mechanisms. We delve into the involvement of CaMKII in the retinal signal transduction pathways and discuss the correlation between CaMKII and calcium overload. Furthermore, we elaborate the therapeutic trials targeting CaMKII, and introduce recent developments in the zone of CaMKII inhibitors. These findings would enrich our knowledge of CaMKII, and shed light on the development of a therapeutic target for degenerative retinopathy.
Dynamics analysis and optimal control of delayed SEIR model in COVID-19 epidemic
Authors: Liu Chongyang , Gao Jie , Kanesan Jeevan
Published: May 2024

The coronavirus disease 2019 (COVID-19) remains serious around the world and causes huge deaths and economic losses. Understanding the transmission dynamics of diseases and providing effective control strategies play important roles in the prevention of epidemic diseases. In this paper, to investigate the effect of delays on the transmission of COVID-19, we propose a delayed SEIR model to describe COVID-19 virus transmission, where two delays indicating the incubation and recovery periods are introduced. For this system, we prove its solutions are nonnegative and ultimately bounded with the nonnegative initial conditions. Furthermore, we calculate the disease-free and endemic equilibrium points and analyze the asymptotical stability and the existence of Hopf bifurcations at these equilibrium points. Then, by taking the weighted sum of the opposite number of recovered individuals at the terminal time, the number of exposed and infected individuals during the time horizon, and the system cost of control measures as the cost function, we present a delay optimal control problem, where two controls represent the social contact and the pharmaceutical intervention. Necessary optimality conditions of this optimal control problem are exploited to characterize the optimal control strategies. Finally, numerical simulations are performed to verify the theoretical analysis of the stability and Hopf bifurcations at the equilibrium points and to illustrate the effectiveness of the obtained optimal strategies in controlling the COVID-19 epidemic.
Efficient and secure privacy protection scheme and consensus mechanism in MEC enabled e-commerce consortium blockchain
Authors: Li Guangshun , Wu Haoyang , Wu Junhua , Li Zhenqiang
Published: May 2024

The application of blockchain technology to the field of e-commerce has solved many dilemmas, such as low transparency of transactions, hidden risks of data security and high payment costs. Mobile edge computing(MEC) can provide computational power for blockchain, and can meet the demand for high real-time and low latency in e-commerce transaction systems. However, there are still some constraints in the MEC enabled e-commerce consortium blockchain, such as the leakage of user privacy information, low security of consensus algorithm and other security issues. In this paper, we propose a secure transaction model suitable for MEC enabled e-commerce consortium blockchain, aiming to ensure the efficiency of system transaction processing while improving the security of users’ privacy information and transaction data. The model adopts the lightweight Paillier encryption algorithm to protect the security of user privacy information and transaction data to prevent the leakage of user privacy information, and optimizes the security of leader election phase of Raft consensus algorithm by introducing the shamir secret sharing protocol to improve the anti-Byzantine failure capabilities of Raft consensus algorithm. The effectiveness of the scheme proposed in this paper is demonstrated by experimental simulations.
Towards a natural treatment for mania: red onion husk extract modulates neuronal resilience, redox signalling, and glial activation
Authors: Ekeanyanwu Chukwuma Raphael , Ekeanyanwu Chidinma Lynda , Ugochukwu Kingsley Nnaemeka
Published: May 2024

Background

Red onion husk, a readily available agricultural waste material, contains diverse bioactive compounds with potential health benefits. This study aimed to assess the safety and therapeutic potential of red onion husk extract in managing manic-like symptoms and associated neurochemical dysfunctions.

Methods

Acute and repeated oral dose studies were conducted in mice and rats to evaluate the safety profile of the extract. FT-IR analysis identified functional groups in the extract, while GC-MS analysis identified specific bioactive compounds in the flavonoid-rich fraction. A ketamine-induced manic behaviour model in Wistar rats was employed to assess the extract’s efficacy in attenuating manic-like symptoms. Behavioural and neurochemical analyses were performed to further investigate the extract’s effects.

Results

The extract demonstrated a favourable safety profile in both acute and repeated dose studies. FT-IR analysis revealed a complex mixture of organic compounds, including hydroxyl groups, alkynes/nitriles, aromatic and non-aromatic C = C bonds, amines, and polysaccharides. GC-MS analysis identified 17 bioactive compounds, including five-methyl-2-phenylindolizine, methadone N-oxide, and 3-phenylthiane, S-oxide. Ketamine administration significantly increased oxidative stress markers, TBARS, and suppressed antioxidant enzyme activities (SOD, GPx, CAT) in both the cerebral cortex and hippocampus, alongside elevated acetylcholinesterase (AchE) activity, indicating enhanced neuronal excitability. Pre-treatment with FRF (25 mg/kg) effectively mitigated ketamine-induced oxidative stress, as evidenced by reduced TBARS levels and partially restored SOD and GPx activities. Interestingly, FRF significantly increased CAT activity (p < 0.001), potentially suggesting an additional compensatory mechanism. Notably, FRF pre-treatment also counteracted ketamine-upregulated AchE activity, offering neuroprotection against heightened neuronal excitability.

Conclusion

Red onion husk extract exhibits a favourable safety profile and exerts potent antioxidant and neuroprotective effects, possibly through modulating Nrf2 signalling pathways. Its ability to counteract ketamine-induced oxidative stress and neuronal hyperactivity highlights its potential as a complementary therapeutic strategy for managing manic episodes in bipolar disorder. Further research is warranted to elucidate the precise molecular mechanisms underlying FRF’s action and explore its clinical efficacy in human studies.
Long-distance migrations and seasonal movements of meagre (Argyrosomus regius), a large coastal predator, along the Iberian Peninsula coast
Authors: Gandra Miguel , Winkler Alexander C. , Afonso Pedro , Abecasis David
Published: May 2024

Background

The meagre, Argyrosomus regius, is a large coastal predatory fish inhabiting waters from the north-eastern Atlantic and Mediterranean Sea, where it is targeted by commercial and recreational fisheries. Previous genetic studies have found an unexpectedly high population differentiation not only between the Atlantic and the Mediterranean, but also along the Atlantic coast. However, the reasons underpinning this genetic barrier remained unclear. Likewise, even though the species is amongst the world’s largest marine teleosts, knowledge about its movement ecology and migratory behaviour remains notably scarce, and primarily reliant on fisheries-dependent data.

Methods

In this study, we used a combination of acoustic telemetry and pop-up satellite archival tags to investigate the movements of 22 adult meagre (70–143 cm total length) along the Southwestern coast of the Iberian Peninsula.

Results

Our results strongly suggest that the previously reported genetic differentiation is not maintained by limited adult dispersal/movement, as hypothesized. On the contrary, we documented some of the longest individual annual migrations ever recorded for a coastal teleost, up to > 2000 km, with frequent back-and-forth movements between the West and Southern Iberian coasts. Moreover, their detected regional movement patterns support the existence of a marked seasonal behavioural shift, with individuals being less active and moving to deeper waters during winter, and are consistent with spawning philopatry associated to their summer reproductive movements. Finally, we identified putative aggregation areas that may harbour important feeding/overwintering grounds.

Conclusions

These findings shed new light on the movement and behaviour patterns of meagre that may be of particular importance for the conservation and spatial management of this species throughout its range, and open the door to further research on functional connectivity.
The influence of immediate occlusal loading on micro/nano-structure of peri-implant jaw bone in rats
Authors: Yorioka Hiroaki , Otsu Yuto , Suzuki Ryu , Matsunaga Satoru , Nakano Takayoshi , Abe Shinichi , Sasaki Hodaka
Published: May 2024

Purpose

The objective of the present study was to ascertain the effect of immediate occlusal loading after implant placement on osseointegration and the micro/nanostructure of the surrounding bone.

Methods

After extraction of a rat maxillary right second molar, an implant was placed immediately with initial fixation (2 N< ). The implants were placed to avoid occlusal loading due to mastication, and in the loaded group, a superstructure was fabricated and subjected to occlusal loading. Bone morphometry, collagen fiber anisotropy, and biological apatite (BAp) crystallite alignment were quantitatively evaluated in both groups after extraction and fixation of the jaw bone at Days 7 and 21 after surgery.

Results

Osseointegration was observed in both groups. Bone morphometry showed significant differences in bone volume, trabecular number, trabecular thickness and bone mineral density (BMD) at Days 21 postoperatively (P < 0.05). A significant difference was also found in the trabecular separation at Days 7 postoperatively (P < 0.05). In the evaluation of collagen fiber anisotropy, collagen fiber bundles running differently from the existing bone were observed in both groups. In terms of BAp crystallite alignment, a specific structure was observed in the reconstructed new bone after implantation, and preferential orientation of BAp crystallite alignment was observed in the longitudinal direction of the implants in the Day 21 postoperative loaded group.

Conclusion

When sufficient initial fixation is achieved at the time of dental implant placement, then the applied masticatory load may contribute to rapidly achieving not only bone volume, but also adequate bone quality after implant placement.
Relation between nutritional status on clinical outcomes of critically ill patients: emphasizing nutritional screening tools in a prospective cohort investigation
Authors: Moghaddam Omid Moradi , Emam Masoumeh Hosseinzadeh , Irandoost Pardis , Hejazi Mahdi , Iraji Zeinab , Yazdanpanah Leila , Mirhosseini Seyedeh Farnaz , Mollajan Abolfazl , Lahiji Mohammad Niakan
Published: May 2024

Background

Malnutrition is a significant concern reported in adult critically ill patients, yet there is no gold standard to assess nutritional status in this population. This study examines the association between nutritional status and clinical outcomes in intensive care unit (ICU) patients using nutritional risk assessment tools and aims to look for the best tool.

Method

In a single-center prospective cohort study among 165 patients, the predictive performance of high or low malnutrition risk assessed by Nutritional Risk Screening (NRS), Modified Nutrition Risk in Critically Ill (m-NUTRIC), Mini-Nutritional-Assessment Short-Form (MNA-SF), Controlling Nutritional status (CONUT), and Prognostic Nutritional Index (PNI) were evaluated and compared for mortality, organ failure, length of hospitalization, and mechanical ventilation (MV).

Results

Different assessment tools showed various nutritional statuses. m-NUTRIC and NRS-2002 were found to be associated more strongly relative to other tools with mortality (RR = 1.72; 95% CI, 1.42–2.08) and (RR = 1.37; 95% CI, 1.08–1.72), organ failure (RR = 1.69; 95% CI, 1.44–1.96) and (RR = 1.22; 95% CI, 0.99–1.48), MV (RR = 1.46; 95% CI, 1.27–1.65) and (RR = 1.21; 95% CI, 1.04–1.39) respectively. There was no correlation between malnutrition levels assessed by mentioned tools except for NRS-2002 and length of hospitalization. In predicting mortality or illness severity, the cut points were different for some tools like NUTRIC-score and all assessed outcomes (3.5), MNA-SF and mortality (6.5), CONUT with mortality, and MV (6.5).

Conclusions

A considerable proportion of patients admitted to the ICU are at high risk for malnutrition. Compared to other tools, m-NUTRIC and NRS-2002 proved superior in predicting clinical outcomes in critically ill patients. Other tools overestimated the risk of malnutrition in the ICU so couldn’t predict clinical outcomes correctly.