bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring non-surgical alternatives for low to intermediate-grade in situ ductal carcinoma of the breast using vacuum-assisted excision: the VACIS protocol
Authors: Nicosia Luca , Mariano Luciano , Latronico Antuono , Bozzini Anna Carla , Bellerba Federica , Gaeta Aurora , Pesapane Filippo , Mazzarol Giovanni , Fusco Nicola , Corso Giovanni , Sangalli Claudia , Gialain Cristian , Lazzeroni Matteo , Raimondi Sara , Cassano Enrico
Published: September 2024

Background

Surgery is still the standard treatment for breast lesions such as in situ ductal carcinoma (DCIS); however, its survival benefit is minimal, particularly for low-grade DCIS. Surgical complications and related depression status can adversely affect patients’ quality of life. Approximately 25% of breast cancer (BC) cases are in situ forms, with DCIS making up 90% of these. Low and intermediate-grade DCIS often grow slowly and do not always progress clinically significant diseases. Identifying non-invasive lesions could help prevent overtreatment. In this context, new diagnostic tools like vacuum-assisted excision (VAE) could enhance the management of these conditions.

Methods

The prospective VACIS study explores the role of VAE in ensuring the absence of pathology at subsequent surgery and reducing the diagnostic underestimation of breast biopsies for microcalcifications. Patients with suspicious breast microcalcifications up to 15 mm, who are candidates for stereotactic biopsy, will be enrolled and randomised into two groups. The control group will complete the biopsy with typical sampling, aiming to collect some microcalcifications from the target, while the experimental group will focus on the complete removal of the biopsy target (confirmed by mammography on the biopsy table), followed by a second sequence of cleaning samples. Radiograms will confirm lesion removal. Pathologic outcomes at surgery will be compared between the groups, and the percentage of underestimation will be assessed. The sample size is calculated to be 70 patients per group, using statistical tests and multivariate logistic models to detect a significant difference in the absence of pathology. Data collected will include patient age, lesion characteristics, and details of the biopsy, pathology and surgery.

Discussion

Current surgical treatments for low-and sometimes intermediate-grade DCIS offer limited survival benefits and may hurt patients’ quality of life due to surgery-related complications and associated depression. These lesions often grow slowly and might not become clinically significant, suggesting a need to avoid overtreatment. Improved diagnostics procedures, such as VAE, could help distinguish non-invasive from potentially invasive lesions, reduce biopsy underestimation, enable personalised management and optimise treatment strategies. This study hypothesises that VAE could be a viable alternative to surgery, capable of removing pathology during the biopsy procedure.

Clinical trial registration

Clinicaltrials.gov, identifier NCT05932758.
Advancements in rapid diagnostics and genotyping of Piscirickettsia salmonis using Loop-mediated Isothermal Amplification
Authors: Isla Adolfo , Aguilar Marcelo , Flores-Martin Sandra N. , Barrientos Claudia A. , Soto-Rauch Genaro , Mancilla-Schulz Jorge , Almendras Felipe , Figueroa Jaime , Yañez Alejandro J.
Published: September 2024

Introduction

Piscirickettsia salmonis, the causative agent of Piscirickettsiosis, poses a significant threat to the Chilean aquaculture industry, resulting in substantial economic losses annually. The pathogen, first identified as specie in 1992, this pathogen was divided into two genogroups: LF-89 and EM-90, associated with different phenotypic mortality and pathogenicity. Traditional genotyping methods, such as multiplex PCR, are effective but limited by their cost, equipment requirements, and the need for specialized expertise.

Methods

This study validates Loop-mediated Isothermal Amplification (LAMP) as a rapid and specific alternative for diagnosing P. salmonis infections. We developed the first qPCR and LAMP assay targeting the species-conserved tonB receptor gene (tonB-r, WP_016210144.1) for the specific species-level identification of P. salmonis. Additionally, we designed two genotyping LAMP assays to differentiate between the LF-89 and EM-90 genogroups, utilizing the unique coding sequences Nitronate monooxygenase (WP_144420689.1) for LF-89 and Acid phosphatase (WP_016210154.1) for EM-90.

Results

The LAMP assays demonstrated sensitivity and specificity comparable to real-time PCR, with additional benefits including rapid results, lower costs, and simplified operation, making them particularly suitable for field use. Specificity was confirmed by testing against other salmonid pathogens, such as Renibacterium salmoninarum, Vibrio ordalii, Flavobacterium psychrophilum, Tenacibaculum maritimum, and Aeromonas salmonicida, with no cross-reactivity observed.

Discussion

The visual detection method and precise differentiation between genogroups underscore LAMP's potential as a robust diagnostic tool for aquaculture. This advancement in the specie detection (qPCR and LAMP) and genotyping of P. salmonis represents a significant step forward in disease management within the aquaculture industry. The implementation of LAMP promises enhanced disease surveillance, early detection, and improved management strategies, ultimately benefiting the salmonid aquaculture sector.
Microbiota profile in organs of the horseflies (Diptera: Tabanidae) in Northeastern China
Authors: Qiu Hong-Yu , Lv Qing-Bo , Wang Chun-Ren , Ju Hao , Luo Chun-Feng , Liu Shun-Shuai , Na Mu-Han , Chang Qiao-Cheng , Jiang Jia-Fu
Published: September 2024

Tabanids, commonly known as horseflies and belonging to the family Tabanidae, are blood-feeding arthropods (BFA) found worldwide. They are known for their ability to mechanically and biologically transmit various animal pathogens. Tabanids are potential vectors for diseases such as Francisella tularensis, Anaplasma marginale, Theileria spp., and contributors to lumpy skin diseases. Despite their involvement in common BFA studies, tabanids have not been extensively explored in microbiome research. In this study, the microbiota structure and composition in various organs of four distinct genera of tabanids: Atylotus, Haematopota, Tabanus, and Hybomitra were examined. High-throughput sequencing of the bacterial 16S rRNA gene was performed to gain insights into the microbial communities associated with the different tabanid species. Result display that microbiota composition and diversity, including Firmicutes, Proteobacteria, and Bacteroidetes, varied significantly among the different organs, with the ovaries exhibiting significantly higher diversity. Apart from the Haematopota genus, Tenericutes were enriched in the midgut of other tabanid species, whereas the Malpighian tubules exhibited a higher abundance of Bacteroides. Notably, the ovarian microbiota structure was conserved among the four tabanid species, indicating its potential association with reproductive development. Evaluation of the potential pathogen risk revealed putative pathogens in over 100 genera associated with these tabanid commensal organisms. Twenty genera were annotated as zoonotic agents with a high abundance of Citrobacter and Brucella, highlighting the presence of this important group of zoonotic pathogens. Functional predictions of vector-microbiota interactions indicate that microbiota significantly affects vector biological traits and can influence pathogen transmission via direct interactions or by regulating host immunity and nutrition. For the first time, the distribution characteristics and functions of four genera of horsefly microbiota were analyzed, revealing the presence of multiple potential pathogenic microorganisms. These findings provide valuable insights for future research and the development of symbiotic-based strategies to control insect-borne diseases among tabanids.
African swine fever virus RNA polymerase subunits C315R and H359L inhibition host translation by activating the PKR-eIF2a pathway and suppression inflammatory responses
Authors: Yang Saixia , Wang Yiwang , Yang Jifei , Tian Zhancheng , Wu Mengli , Sun Hualin , Zhang Xiaoqiang , Zhao Yaru , Luo Jianxun , Guan Guiquan , Yin Hong , Hao Rongzeng , Niu Qingli
Published: September 2024

ASFV C315R is homologous to the transcription factor TFIIB of large unclassified DNA viruses, and H359L is identical to the subunit 3 (RPB3) of eukaryotic RNA polymerase II. The C315R and H359L may play an important role in ASFV replication and transcription. Here, we evaluated the biological function of the C315R and H359L genes during virus replication in vitro and during infection in pigs. Results showed that C315R and H359L are highly conserved among ASFV genotype II strains; quantitative PCR (qPCR) and western blotting analyses revealed that C315R and H359L are early transcribed genes prior to viral DNA replication, but their protein expression is delayed. The immunofluorescence and western blotting analysis revealed that both proteins localized in the cell cytoplasm and nucleus at 24 h post infection, however, pH359L was mainly detected in the cell cytoplasm. Furthermore, overexpression of pH359L in MA104 cells significantly increased viral titer, RNA transcription levels, and viral protein expression levels, while overexpression of pC315R slightly enhanced ASFV replication. In contrast, siRNA targeting ASFV-H359L or C315R reduced replication efficiency in porcine macrophage culture compared to the parent ASFV-CN/SC/2019, demonstrating that C315R and H359L genes are necessary for ASFV replication. Finally, the functional role of C315R or H359L on PKR and eIF2α phosphorylation status and SG formation, as well as cytokine production were evaluated. These studies demonstrated that C315R and H359L are involved in virus replication processes in swine and play important roles in ASFV replication.
Native mechano-regulative matrix properties stabilize alternans dynamics and reduce spiral wave stabilization in cardiac tissue
Authors: Erhardt Julia , Ludwig Sebastian , Brock Judith , Hörning Marcel
Published: September 2024

The stability of wave conduction in the heart is strongly related to the proper interplay between the electrophysiological activation and mechanical contraction of myocytes and extracellular matrix (ECM) properties. In this study, we statistically compare bioengineered cardiac tissues cultured on soft hydrogels (E≃12 kPa) and rigid glass substrates by focusing on the critical threshold of alternans, network-physiological tissue properties, and the formation of stable spiral waves that manifest after wave breakups. For the classification of wave dynamics, we use an improved signal oversampling technique and introduce simple probability maps to identify and visualize spatially concordant and discordant alternans as V- and X-shaped probability distributions. We found that cardiac tissues cultured on ECM-mimicking soft hydrogels show a lower variability of the calcium transient durations among cells in the tissue. This lowers the likelihood of forming stable spiral waves because of the larger dynamical range that tissues can be stably entrained with to form alternans and larger spatial spiral tip movement that increases the chance of self-termination on the tissue boundary. Conclusively, we show that a dysfunction in the excitation–contraction coupling dynamics facilitates life-threatening arrhythmic states such as spiral waves and, thus, highlights the importance of the network-physiological interplay between contractile myocytes and the ECM.
Meta-analysis of resting-state fMRI in cervical spondylosis patients using AES-SDM
Authors: Zhang Qin , Ding Hui
Published: September 2024

Background

Resting-state functional magnetic resonance imaging (rs-fMRI) reveals diverse neural activity patterns in cervical spondylosis (CS) patients. However, the reported results are inconsistent. Therefore, our objective was to conduct a meta-analysis to synthesize the findings from existing rs-fMRI studies and identify consistent patterns of neural brain activity alterations in patients with CS.

Materials and methods

A systematic search was conducted across PubMed, Web of Knowledge, Embase, Google Scholar, and CNKI for rs-fMRI studies that compared CS patients with healthy controls (HCs), up to January 28, 2024. Significant cluster coordinates were extracted for comprehensive analysis.

Results

We included 16 studies involving 554 CS patients and 488 HCs. CS patients demonstrated decreased brain function in the right superior temporal gyrus and left postcentral gyrus, and increased function in the left superior frontal gyrus. Jackknife sensitivity analysis validated the robustness of these findings, and Egger’s test confirmed the absence of significant publication bias (p > 0.05). Meta-regression showed no significant impact of age or disease duration differences on the results.

Conclusion

This meta-analysis confirms consistent alterations in specific brain regions in CS patients, highlighting the potential of rs-fMRI to refine diagnostic and therapeutic strategies.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42024496263.
Clinical application of sparse canonical correlation analysis to detect genetic associations with cortical thickness in Alzheimer’s disease
Authors: Kim Bo-Hyun , Seo Sang Won , Park Yu Hyun , Kim JiHyun , Kim Hee Jin , Jang Hyemin , Yun Jihwan , Kim Mansu , Kim Jun Pyo
Published: September 2024

Introduction

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by cerebral cortex atrophy. In this study, we used sparse canonical correlation analysis (SCCA) to identify associations between single nucleotide polymorphisms (SNPs) and cortical thickness in the Korean population. We also investigated the role of the SNPs in neurological outcomes, including neurodegeneration and cognitive dysfunction.

Methods

We recruited 1125 Korean participants who underwent neuropsychological testing, brain magnetic resonance imaging, positron emission tomography, and microarray genotyping. We performed group-wise SCCA in Aβ negative (−) and Aβ positive (+) groups. In addition, we performed mediation, expression quantitative trait loci, and pathway analyses to determine the functional role of the SNPs.

Results

We identified SNPs related to cortical thickness using SCCA in Aβ negative and positive groups and identified SNPs that improve the prediction performance of cognitive impairments. Among them, rs9270580 was associated with cortical thickness by mediating Aβ uptake, and three SNPs (rs2271920, rs6859, rs9270580) were associated with the regulation of CHRNA2, NECTIN2, and HLA genes.

Conclusion

Our findings suggest that SNPs potentially contribute to cortical thickness in AD, which in turn leads to worse clinical outcomes. Our findings contribute to the understanding of the genetic architecture underlying cortical atrophy and its relationship with AD.
Acute myeloid leukemia cells adhere to bone marrow and acquire chemoresistance by downregulating UNC5B expression
Authors: Teng Teng , Ren Liping , Xiao Jilong , Shi Zhiyu , Li Lanbo , Song Chunhong
Published: September 2024

Acute myeloid leukemia (AML) is a malignant tumor of the hematological system. Because of its characteristics of recurrence, refractory and chemoresistance, new therapeutic targets need to be identified. Adhesion and proliferation are characteristics of AML cells, and critical steps in inducing chemotherapy resistance. In this study, we reported that UNC5B inhibits AML cell bone marrow adhesion, inhibits AML cell proliferation and increases sensitivity to chemotherapy. Mechanistically, RNA sequencing (RNA-seq) and experimental results revealed that overexpression of UNC5B inhibits adhesion and proliferation signaling pathways and inhibits the expression of MPZL1, CLDN23, IGF2 and WNT7B. In conclusion, our findings suggest that UNC5B serves as a prognostic indicator and a potential therapeutic target for AML.
Case report: IORT as an alternative treatment option for breast cancer patients with difficulty staying still
Authors: Bhimani Fardeen , McEvoy Maureen , Chen Yu , Gupta Anjuli , Pastoriza Jessica , Fruchter Shani , Bitan Zachary C. , Tomé Wolfgang A. , Mehta Keyur , Fox Jana , Feldman Sheldon
Published: September 2024

Background

Administering radiation therapy to individuals with intellectual disabilities (ID) and psychiatric patients taking antipsychotics poses challenges, especially with whole breast irradiation (WBI) due to difficulty staying still (DSS). In such scenarios, intraoperative radiotherapy (TARGIT-IORT) provides an alternative. Although prior studies have shown its applicability in special cases where WBI may be contraindicated, there is a paucity of literature emphasizing its role in patients with ID and psychiatric conditions who have DSS. Therefore, our case series aims to highlight the applicability of administering TARGIT-IORT in such patients.

Case reports

Four breast cancer patients underwent lumpectomy and TARGIT-IORT. Among them, two patients had ID, with one experiencing a decreased range of motion. The other two had psychiatric disorders, including schizophrenia and bipolar disorder, both manifesting involuntary movements and DSS. Three patients had invasive ductal carcinoma (IDC), and one had invasive lobular carcinoma (ILC). All patients undergoing TARGIT-IORT tolerated the procedure well. Notably, none of the patients exhibited evidence of disease on follow-up.

Conclusion

Our study underscores the potential use of TARGIT-IORT as a viable treatment option for breast cancer patients with intellectual and psychiatric disabilities. Unlike traditional EBRT, TARGIT-IORT offers a single radiation dose, addressing challenges associated with compliance or DSS. Our findings demonstrate positive outcomes and tolerance, especially in patients where standard oncologic procedures are difficult to achieve. TARGIT-IORT could also benefit breast cancer patients with concurrent movement disorders like Parkinson’s disease and other movement disorders. Nonetheless, future studies are needed to reinforce its applicability for patients with DSS.
Extracellular vesicles from cancer cell lines of different origins drive the phenotype of normal oral fibroblasts in a CAF-like direction
Authors: Søland Tine M. , Lipka Aleksandra , Ruus Ann-Kristin , Molværsmyr Ann-Kristin , Galtung Hilde K. , Haug Trude M.
Published: September 2024

Introduction

Normal oral fibroblasts (NOFs) are located in the connective tissue of the oral mucosa. The NOFs play an important role in wound healing, tumor progression, and metastasis. They are subjected to influence by external and internal stimuli, among them extracellular vesicles (EVs), that are considered as important players in cell to cell communication, especially in carcinogenesis and metastatic processes. During tumorigenesis, stromal NOFs may undergo activation into cancer-associated fibroblasts (CAFs) that modify their phenotype to provide pro-oncogenic signals that in turn facilitate tumor initiation, progression, and metastasis. The aim of the study was to reveal the effect of EVs derived from local (oral squamous cell carcinoma – OSCC) and distant (pancreatic adenocarcinoma – PDAC; malignant melanoma brain metastasis – MBM) cancer origin on NOFs and their possible change into a CAF-like direction.

Methods

The effect of each of the cancer EV types on NOFs proliferation, viability, and migration was tested. Also, changes in gene expression of the well-established CAF biomarkers ACTA2, FAP, PDGFR, and two putative CAF biomarkers, the Ca2+- activated ion channels ANO1 and KCNMA, were studied.

Results

Obtained results indicate that NOFs receive and process signals transmitted by EVs originating from both OSCC, PDAC, and MBM. The fibroblast response was dependent on EV origin and concentration, and duration of EV exposure.

Conclusion

The present results indicate that the molecular cargo of the EVs direct NOFs towards a pro-tumorigenic phenotype.
Knowledge mapping analysis of ground glass nodules: a bibliometric analysis from 2013 to 2023
Authors: Wang Linfeng , Maolan Ayidana , Luo Yue , Li Yue , Liu Rui
Published: September 2024

Background

In recent years, the widespread use of computed tomography (CT) in early lung cancer screening has led to an increase in the detection rate of lung ground glass nodules (GGNs). The persistence of GGNs, which may indicate early lung adenocarcinoma, has been a focus of attention for scholars in the field of lung cancer prevention and treatment in recent years. Despite the rapid development of research into GGNs, there is a lack of intuitive content and trend analyses in this field, as well as a lack of detailed elaboration on possible research hotspots. The objective of this study was to conduct a comprehensive analysis of the knowledge structure and research hotspots of lung ground glass nodules over the past decade, employing bibliometric methods.

Method

The Web of Science Core Collection (WoSCC) database was searched for relevant ground-glass lung nodule literature published from 2013-2023. Bibliometric analyses were performed using VOSviewer, CiteSpace, and the R package “bibliometrix”.

Results

A total of 2,218 articles from 75 countries and 2,274 institutions were included in this study. The number of publications related to GGNs has been high in recent years. The United States has led in GGNs-related research. Radiology has one of the highest visibilities as a selected journal and co-cited journal. Jin Mo Goo has published the most articles. Travis WD has been cited the most frequently. The main topics of research in this field are Lung Cancer, CT, and Deep Learning, which have been identified as long-term research hotspots. The GGNs-related marker is a major research trend in this field.

Conclusion

This study represents the inaugural bibliometric analysis of applied research on ground-glass lung nodules utilizing three established bibliometric software. The bibliometric analysis of this study elucidates the prevailing research themes and trends in the field of GGNs over the past decade. It also furnishes pertinent recommendations for researchers to provide objective descriptions and comprehensive guidance for future related research.
A novel opioid/pramipexole combination treatment for the management of acute pain: a pilot study
Authors: Girardi Cara , Duronio Joseph , Patton Ryan , O’Brien Kevin , Clemens Stefan , Brewer Kori L.
Published: September 2024

Purpose

Despite their dangerous side effects, opioid drugs remain a standard of care for moderate to severe pain with few alternatives. Strategies to maintain the analgesic effects of opioids while minimizing the associated risks are needed. Pre-clinical studies have shown using a dopamine 3 receptor (D3R) agonist as an adjuvant to morphine provides superior analgesia against painful stimuli compared to morphine alone. Our objective was to test if adjunct treatment with a D3R agonist can lead to a reduction in opioid use while maintaining effective analgesia.

Patients and methods

This study was set up as a double-blinded, placebo-controlled randomized trial. Enrollment included acute renal colic patients presenting to the emergency department, from which patients were randomized to either the “control” or “study arm”. The control group received standard treatment of care (morphine, 0.1 mg/kg; i.v.) and an oral placebo pill. The experimental group received half-dosed morphine and oral pramipexole pill (0.25 mg). Pain measurements including a numerical pain scale and visual analog scale were collected from enrollees at baseline and every subsequent 15 min.

Results

A total of 19 patients completed the study, 10 in the experimental arm and 9 in the control arm. During the study period, effective analgesia (50% decrease from baseline) was achieved in 80% of patients in the experimental arm vs. 33.3% in the control arm.

Conclusion

Our pilot clinical trial demonstrated that D3R recruitment can serve as an effective adjuvant to low-dose morphine for control of renal colic pain and potentially other acute pain conditions.

Clinical Trial Registration

ClinicalTrials.gov, identifier, (NCT04160520).
Lithocarpus polystachyus Rehd. ameliorates cerebral ischemia/reperfusion injury through inhibiting PI3K/AKT/NF-κB pathway and regulating NLRP3-mediated pyroptosis
Authors: Liu Daifang , Wu Wendan , Wang Tingting , Zhan Guiyu , Zhang Yuandong , Gao Jianmei , Gong Qihai
Published: September 2024

Introduction

Ischemic stroke (IS) is a serious threat to human life and health, and cerebral ischemia/reperfusion injury (CIRI) exacerbates IS by enhancing neuroinflammation and oxidative stress. Sweet tea (ST) comprises several bioactive components, such as phlorizin, trilobatin, and phloretin, with diverse pharmacological activities. However, it remains uncertain whether ST can confer protection against CIRI. In this study, we aimed to investigate the impact and potential underlying mechanism of ST in the context of CIRI.

Methods

CIRI model were established in male sprague dawley (SD) rats. The neurobehavioral assessment, the volume of cerebral infarction and the morphology of neurons were measured to complete the preliminary pharmacodynamic study. The therapeutic targets and pathways of ST on IS were obtained by protein-protein interaction, molecular docking and Metascape database. The predicted results were further verified in vivo.

Results

Our results revealed that ST treatment significantly ameliorated brain damage in rats subjected to CIRI by mitigating mitochondrial oxidative stress and neuroinflammation. Additionally, we identified the PI3K/AKT/NF-κB pathway and the NLRP3-mediated pyroptosis axis as crucial processes, with molecular docking suggested direct interactions between the main compounds of ST and NLRP3.

Conclusion

ST safeguards against CIRI-induced neuronal loss, neuroinflammation and oxidative stress through the inhibition of the PI3K/AKT/NF-κB pathway and the regulation of NLRP3-mediated pyroptosis.
Apoptosis, autophagy, ferroptosis, and pyroptosis in cisplatin-induced ototoxicity and protective agents
Authors: Dai Dingyuan , Chen Chao , Lu Chen , Guo Yu , Li Qi , Sun Chen
Published: September 2024

Cisplatin is widely used to treat various solid tumors. However, its toxicity to normal tissues limits its clinical application, particularly due to its ototoxic effects, which can result in hearing loss in patients undergoing chemotherapy. While significant progress has been made in preclinical studies to elucidate the cellular and molecular mechanisms underlying cisplatin-induced ototoxicity (CIO), the precise mechanisms remain unclear. Moreover, the optimal protective agent for preventing or mitigating cisplatin-induced ototoxicity has yet to be identified. This review summarizes the current understanding of the roles of apoptosis, autophagy, ferroptosis, pyroptosis, and protective agents in cisplatin-induced ototoxicity. A deeper understanding of these cell death mechanisms in the inner ear, along with the protective agents, could facilitate the translation of these agents into clinical therapeutics, help identify new therapeutic targets, and provide novel strategies for cisplatin-based cancer treatment.
SAL0114: a novel deuterated dextromethorphan-bupropion combination with improved antidepressant efficacy and safety profile
Authors: Xiao Ying , Hu Xuefeng , Xing Wei , Yan Jie , Wang Ruhuan , Li Xiaoqing , Li Jiahuan , Zhang Zhixin , Sun Jingchao , Wu Junjun
Published: September 2024

Background

Esketamine, the first Food and Drug Administration-approved fast-acting antidepressant, has limited use because of its addictive properties. Although the combination of dextromethorphan and bupropion partially addresses the limitations of esketamine, concerns remain regarding neurologic side effects related to dextromethorphan metabolites, and seizure risks associated with high-dose bupropion. SAL0114, a novel formulation combining deuterated dextromethorphan (in which hydrogen atoms are replaced with deuterium) with bupropion, seeks to enhance dextromethorphan stability through deuteration of its metabolic sites. This approach is expected to increase antidepressant efficacy, reduce metabolite-induced safety issues, and allow for lower bupropion dosages.

Methods

Radioligand competition binding assays were used to evaluate the impact of deuterium substitution on the in vitro activity of dextromethorphan and its metabolite, dextrorphan. In vitro hepatic microsomal stability and in vivo mouse pharmacokinetic assays were performed to assess the effects of deuteration on dextromethorphan stability. Two mouse models of behavioral despair were used to determine the antidepressant and synergistic effects of deuterated dextromethorphan and bupropion. Additionally, a reserpine-induced hypothermia rat model and an ammonia-induced cough mouse model were used to assess the in vivo effects from a pathological perspective.

Results

Deuterated dextromethorphan maintained the same in vitro activity as dextromethorphan while exhibiting twice the metabolic stability both in vitro and in vivo. Combination with bupropion further improved its in vivo stability, increasing the exposure by 2.4 times. The combination demonstrated efficacy and synergistic effects in all tested animal models, showing superior efficacy compared with the dextromethorphan-bupropion combination.

Conclusion

Deuteration improved dextromethorphan metabolic stability without altering its in vitro activity. Bupropion enhanced this stability and synergistically boosted the antidepressant effect by increasing deuterated dextromethorphan exposure in vivo. This enhanced metabolic stability suggests a reduction in dextromethorphan metabolites associated with clinical neurological side effects. Consequently, SAL0114 is hypothesized to offer improved efficacy and safety compared with the non-deuterated combination, potentially allowing for lower bupropion dosages. Further clinical studies are required to confirm these preclinical findings.
Protonophore treatment augments energy expenditure in mice housed at thermoneutrality
Authors: Sadler Daniel G. , Landes Reid D. , Treas Lillie , Sikes James , Porter Craig
Published: September 2024

Background

Sub-thermoneutral housing increases facultative thermogenesis in mice, which may mask the pre-clinical efficacy of anti-obesity strategies that target energy expenditure (EE). Here, we quantified the impact of protonophore treatment on whole-body energetics in mice housed at 30°C.

Methods

C57BL/6J mice (n = 48, 24M/24F) were housed at 24°C for 2 weeks; 32 (16M/16F) were then transitioned to 30°C for a further 4 weeks. Following 2 weeks acclimation at 30°C, mice (n = 16 per group, 8M/8F) received either normal (0 mg/L; Control) or supplemented (400 mg/L; 2,4-Dinitrophenol [DNP]) drinking water. Mice were singly housed in metabolic cages to determine total EE (TEE) and its components via respiratory gas exchange. Mitochondrial respiratory function of permeabilized liver tissue was determined by high-resolution respirometry.

Results

Transitioning mice from 24°C to 30°C reduced TEE and basal EE (BEE) by 16% and 41%, respectively (both P < 0.001). Compared to 30°C controls, TEE was 2.6 kcal/day greater in DNP-treated mice (95% CI: 1.6–3.6 kcal/day, P < 0.001), which was partly due to a 1.2 kcal/day higher BEE in DNP-treated mice (95% CI: 0.6–1.7 kcal/day, P < 0.001). The absolute TEE of 30°C DNP-treated mice was lower than that of mice housed at 24°C in the absence of DNP (DNP: 9.4 ± 0.7 kcal/day vs. 24°C control: 10.4 ± 1.5 kcal/day). DNP treatment reduced overall body fat of females by 2.9 percentage points versus sex-matched controls (95% CI: 1.3%–4.5%, P < 0.001), which was at least partly due to a reduction in inguinal white fat mass.

Conclusion

Protonophore treatment markedly increases EE in mice housed at 30°C. The magnitude of change in TEE of mice receiving protonophore treatment at 30°C was smaller than that brought about by transitioning mice from 24°C to 30°C, emphasizing that housing temperature must be considered when assessing anti-obesity strategies that target EE in mice.
The relationship between work–family conflict and job burnout among primary and secondary school teachers: the role of depression and cognitive reappraisal
Authors: Li Yue , Ni Xingcan , Zhang Wei , Wang Jianping , Yu Chengfu , Zou Hongyu
Published: September 2024

Background

Primary and secondary school teachers are a high-risk group for job burnout, and how to alleviate their job burnout has become an increasingly urgent issue. Previous studies have paid less attention to the differential effects of the bidirectional interaction between work and family on the job burnout of the teachers. This study aim to explore the different impact of work–family conflict and family–work conflict on job burnout among primary and secondary school teachers, as well as its underlying mechanisms.

Methods

This study selected 2,184 primary and secondary school teachers in China (Mage = 37.26; SD = 9.40) as participants using a random sampling method. Using the SPSS Process 4.0 macro plugin constructed a moderated mediation model, the study explored the relationships between two different forms of work–family conflict, depression, cognitive reappraisal, and job burnout.

Results

The study results indicated that both forms of work–family conflict were significantly positively related to the job burnout, and this relationship was influenced by the mediating role of depression. Furthermore, cognitive reappraisal moderated the relationship between depression and job burnout.

Conclusion

This study revealed the potential pathways influencing job burnout among primary and secondary school teachers in the Chinese cultural context. Focusing on and alleviating work–family conflicts for primary and secondary school teachers is crucial for mitigating their occupational burnout. Additionally, teachers should also carefully and reasonably use cognitive reappraisal as an emotional regulation strategy to adjust the impact of depression on occupational burnout.
The major biogenic amine metabolites in mood disorders
Authors: Yang Jingyi , Yuan Minlan , Zhang Wei
Published: September 2024

Mood disorders, including major depressive disorder and bipolar disorder, have a profound impact on more than 300 million people worldwide. It has been demonstrated mood disorders were closely associated with deviations in biogenic amine metabolites, which are involved in numerous critical physiological processes. The peripheral and central alteration of biogenic amine metabolites in patients may be one of the potential pathogeneses of mood disorders. This review provides a concise overview of the latest research on biogenic amine metabolites in mood disorders, such as histamine, kynurenine, and creatine. Further studies need larger sample sizes and multi-center collaboration. Investigating the changes of biogenic amine metabolites in mood disorders can provide biological foundation for diagnosis, offer guidance for more potent treatments, and aid in elucidating the biological mechanisms underlying mood disorders.
Association between aromatic amines and serum neurofilament light chain as a biomarker of neural damage: a cross-sectional study from NHANES
Authors: Lin Tong , Mao Haiyan , Huang Shanshan , Chen Jialu
Published: September 2024

Background

Aromatic amines (AAs) are a group of compounds widely found in chemical industry, tobacco smoke, and during food processing, with established carcinogenic properties. To date, there have been no reports on the potential neurotoxic effects of adult exposure to AAs. Serum neurofilament light chain (sNfL) is a protein released into the bloodstream following nerve axon injury and has been validated as a reliable biomarker for various neurological diseases. However, there has been no research to investigate the relationship between AAs exposure and sNfL.

Methods

In this study, we selected adults (aged ≥20 years) with data on both AAs and sNfL from the National Health and Nutrition Examination Survey (NHANES) conducted in 2013–2014. We used multivariable linear regression models to explore the correlation between urinary AAs and sNfL.

Results

In total, 510 adult participants with an average age of 43.58 ± 14.74 years were included in the study. Our findings indicate that, based on univariate linear regression and between-group comparative analyses, 1-Aminonaphthalene (1-AN), 2-Aminonaphthalene (2-AN), 4-Aminobiphenyl (4-AN) and o-Anisidine (o-ANI) showed a positive correlation with serum neurofilament light chain (P < 0.05). However, multiple linear regression analysis revealed that only 2-AN exhibited a positive correlation with serum neurofilament light chain (P < 0.05), while the correlations of other compounds with serum neurofilament light chain became non-significant.

Conclusion

Although our cross-sectional study fails to establish causal relationships or determine clinical significance, the findings indicate a potential association between adult exposure to AAs, notably 2-AN, and nerve damage. Consequently, further research is needed to explore the connection between AAs exposure, sNfL, and neurological conditions in adults.
Association between Internet use and depression among older adults in China: the chain-mediating role of volunteer activity participation and friend network
Authors: Liu Yujiang , Li Fang , Sun Jian
Published: September 2024

Background

Depression is a significant burden on individuals and society, which requires our attention and action. As the aging wave collides with digitalization, further research is needed to understand how internet use relates to depression in older adults. This study aimed to investigate whether volunteer activity participation and friend networks played a chain mediating role in this relationship from the perspective of the socioemotional selectivity theory.

Method

This study’s data was derived from the 2018 China Longitudinal Aging Social Survey (CLASS), comprising 5,558 samples. The study employed the OLS model for benchmark regression and multiple robust check methods, including altering variable settings and utilizing the instrumental variable model. In addition, the generalized structural equation model (GSEM) was used to analyze the mechanism.

Result

Using the internet was significantly associated with reduced depression in older adults (coefficient = −0.9321, p < 0.001). The instrumental variable model confirmed this reduction (coefficient = −0.9200, p < 0.001). Moreover, we found that there were three indirect pathways of Internet use on depression among older adults: the mediating role of volunteer activity participation (all p-values <0.001), the mediating role of friend network (all p-values <0.001), and the chain mediating role of both factors (all p-values <0.001).

Conclusion

Based on the research findings, we suggest mobilizing tech-savvy older adults to assist others in adopting digital technology and using the internet. We also suggest that the government could assist in creating older adult-friendly communities. Social workers could collaborate with tech-savvy older adults to organize various voluntary activities, encouraging more senior citizens to participate. In addition, we recommend that the community should consider the form of activities to help older adults make friends first rather than solely focusing on voluntary activities.
Gut Microbiota Diversity of Local Egyptian Cattle Managed in Different Ecosystems
Authors: Aboshady Hadeer M. , Gavriilidou Asimenia , Ghanem Nasser , Radwan Mohamed A. , Elnahas Ahmed , Agamy Rania , Fahim Nadia H. , Elsawy Mohamed H. , Shaarawy Al-Moataz Bellah M. , Abdel-Hafeez Ahmed M. , Kantanen Juha , Ginja Catarina , Makgahlela Mahlako L. , Kugonza Donald R. , Gonzalez-Prendes Rayner , Crooijmans Richard P. M. A.
Published: September 2024

The animal gastrointestinal tract contains a complex microbiome whose composition ultimately reflects the co-evolution of microorganisms with their animal host and their host’s environment. This study aimed to gain insights into the adaptation of the microbiota of local Egyptian cattle to three different ecosystems (Upper Egypt, Middle Egypt, and Lower Egypt) distributed across 11 governorates (with an average of 12 animals per governorate) using amplicon sequencing. We analyzed the microbiota from 136 fecal samples of local Egyptian cattle through a 16S rRNA gene sequencing approach to better understand the fecal microbial diversity of this breed which developed under different ecosystems. An alpha diversity analysis showed that the fecal microbiota of the Egyptian cattle was not significantly diverse across areas, seasons, sexes, or farm types. Meanwhile, microbiota data revealed significant differences in richness among age groups (p = 0.0018). The microbial community differed significantly in the distribution of its relative abundance rather than in richness across different ecosystems. The taxonomic analysis of the reads identified Firmicutes and Actinobacteriota as the dominant phyla, accounting for over 93% of the total bacterial community in Egyptian cattle. Middle Egypt exhibited a different microbial community composition compared to Upper and Lower Egypt, with a significantly higher abundance of Firmicutes and Euryarchaeota and a lower abundance of Actinobacteriota in this region than the other two ecosystems. Additionally, Middle Egypt had a significantly higher relative abundance of the Methanobacteriaceae family and the Methanobrevibacter genera than Lower and Upper Egypt. These results suggest a difference in the adaptation of the fecal microbial communities of Egyptian cattle raised in Middle Egypt. At the genus level, eleven genera were significantly different among the three ecosystems including Bacillus, DNF00809, Kandleria, Lachnospiraceae_NK3A20_group, Methanobrevibacter, Mogibacterium, Olsenella, Paeniclostridium, Romboutsia, Turicibacter, and UCG-005. These significant differences in microbiota composition may impact the animal’s adaptation to varied environments.
Association of Production and Selected Dimensional Conformation Traits in Holstein Friesian Cows
Authors: Kőrösi Zsolt Jenő , Holló Gabriella , Bene Szabolcs , Bognár László , Szabó Ferenc
Published: September 2024

The objective of this study was to estimate the heritability of dairy production traits and that for dimensional traits and to calculate the correlation between the two heritability values in a Holstein Friesian cow herd bred in Hungary. Data of 15,032 Holstein Friesian cows born in the period 2008–2018 from 666 sires were collected for the study in 6 large dairy herds. Among the conformation traits, stature (ST), chest width (CW), body depth (BD), and rump width (RW), and for production traits, in the first lactation of cows, the 305-day milk yield (MY), milk butterfat yield (FY), and milk protein yield (MY) were evaluated. Heritability estimates of ST, CW, BD, and RW were 0.49, 0.25, 0.31, and 0.30, and those of MY, FY, and PY were 0.40, 0.35, and 0.30, respectively. BD and RW had no phenotypic (b = −0.01) or genetic (b = 0.00–0.01) change. The production traits (MY, FY, PY) increased to a greater extent (b = 2.2–43.3) than the examined conformation traits over time. Consequently, it is indicated that the selection for dairy production did not result in an increase in the studied dimensional traits.
Stepwise Imperatives for Improving the Protection of Animals in Research and Education in Canada
Authors: Lavelle Kyrstin , Fouad Karim , Illes Judy
Published: September 2024

In this paper, we review the standard-setting tools of different levels of government in Canada for overseeing the care of animals used in science against a landscape of other international efforts. We find regulatory inconsistencies, argue that the related shortcomings are detrimental to the level of care afforded to animals, and offer suggestions for a centralized and proactive approach that could close the existing gaps. Given the resources, cost, and time it would take to transform the current system into a single cohesive one, the proposed approach is a stepwise one, and begins with the addition of two new Rs—Reflection and Responsiveness—to the existing 3Rs framework: Replacement, Refinement, and Reduction. Reflection emphasizes more continuous and specific attention to progress in the research pathway as it applies to animals than is currently required by institutional review and reporting; Responsiveness speaks to the immediate action that researchers can take responsively to that ongoing evaluation.
The Molecular Mechanisms of Portal Vein Thrombosis in Hepatocellular Carcinoma
Authors: Galasso Linda , Cerrito Lucia , Termite Fabrizio , Mignini Irene , Esposto Giorgio , Borriello Raffaele , Ainora Maria Elena , Gasbarrini Antonio , Zocco Maria Assunta
Published: September 2024

Hepatocellular carcinoma (HCC) represents the sixth most diagnosed cancer worldwide and is the second leading cause of cancer-related death in the world. The association of HCC and portal vein thrombosis (PVT) represents an advanced stage of the tumor. PVT has a prevalence of about 25–50% in HCC, determining poor prognosis and a remarkable reduction in therapeutic perspectives in these patients, leading to severe complications such as ascites, metastasis, an increase in portal hypertension and potentially fatal gastrointestinal bleeding. The aim of this review is to evaluate the molecular mechanisms that are at the basis of PVT development, trying to evaluate possible strategies in the early detection of patients at high risk of PVT.
Biomimetic Layered Hydrogel Coating for Enhanced Lubrication and Load-Bearing Capacity
Authors: Hu Xuxu , Zhao Yu , Cheng Shuai , Zhen Jinming , Jia Zhengfeng , Zhang Ran
Published: September 2024

Biomimetic hydrogel lubrication coatings with high wettability and low friction show great promise in tissue engineering, wound dressing, drug delivery, and intelligent sensing. Inspired by the hierarchical structure of natural cartilage, a layered hydrogel coating was constructed to functionalize rigid polyetheretherketone (PEEK). The layered hydrogel coating features a structural design comprising a top soft layer and a middle robust layer. The porous structure of the top soft hydrogel layer stores water molecules, providing surface lubrication, while the dense structure of the middle robust hydrogel layer offers load-bearing capacity. These synergistic effects of the gradient hydrogel layer endow the PEEK substrate with an ultra-low coefficient of friction (COF~0.010 at 5 N load), good load-bearing capacity (COF~0.031 at 10 N load), and excellent wear resistance (COF < 0.05 at 5 N load after 20,000 sliding cycles). This study introduces a novel design paradigm for robust hydrogel coatings with exceptional lubricity, displaying the potential application in cartilage replacement materials.