bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of necroptosis-related features in diabetic nephropathy and analysis of their immune microenvironent and inflammatory response
Authors: Hu Kaibo , He Ruifeng , Xu Minxuan , Zhang Deju , Han Guangyu , Han Shengye , Xiao Leyang , Xia Panpan , Ling Jitao , Wu Tingyu , Li Fei , Sheng Yunfeng , Zhang Jing , Yu Peng
Published: November 2023

Background: Diabetic nephropathy (DN) was considered a severe microvascular complication of diabetes, which was recognized as the second leading cause of end-stage renal diseases. Therefore, identifying several effective biomarkers and models to diagnosis and subtype DN is imminent. Necroptosis, a distinct form of programmed cell death, has been established to play a critical role in various inflammatory diseases. Herein, we described the novel landscape of necroptosis in DN and exploit a powerful necroptosis-mediated model for the diagnosis of DN.

Methods: We obtained three datasets (GSE96804, GSE30122, and GSE30528) from the Gene Expression Omnibus (GEO) database and necroptosis-related genes (NRGs) from the GeneCards website. Via differential expression analysis and machine learning, significant NRGs were identified. And different necroptosis-related DN subtypes were divided using consensus cluster analysis. The principal component analysis (PCA) algorithm was utilized to calculate the necroptosis score. Finally, the logistic multivariate analysis were performed to construct the necroptosis-mediated diagnostic model for DN.

Results: According to several public transcriptomic datasets in GEO, we obtained eight significant necroptosis-related regulators in the occurrence and progress of DN, including CFLAR, FMR1, GSDMD, IKBKB, MAP3K7, NFKBIA, PTGES3, and SFTPA1 via diversified machine learning methods. Subsequently, employing consensus cluster analysis and PCA algorithm, the DN samples in our training set were stratified into two diverse necroptosis-related subtypes based on our eight regulators’ expression levels. These subtypes exhibited varying necroptosis scores. Then, we used various functional enrichment analysis and immune infiltration analysis to explore the biological background, immune landscape and inflammatory status of the above subtypes. Finally, a necroptosis-mediated diagnostic model was exploited based on the two subtypes and validated in several external verification datasets. Moreover, the expression level of our eight regulators were verified in the singe-cell level and glomerulus samples. And we further explored the relationship between the expression of eight regulators and the kidney function of DN.

Conclusion: In summary, our necroptosis scoring model and necroptosis-mediated diagnostic model fill in the blank of the relationship between necroptosis and DN in the field of bioinformatics, which may provide novel diagnostic insights and therapy strategies for DN.
Differentiation-dependent chromosomal organization changes in normal myogenic cells are absent in rhabdomyosarcoma cells
Authors: Ibarra Joe , Hershenhouse Tyler , Almassalha Luay , Walterhouse David , Backman Vadim , MacQuarrie Kyle L.
Published: November 2023

Myogenesis, the progression of proliferating skeletal myoblasts to terminally differentiated myotubes, regulates thousands of target genes. Uninterrupted linear arrays of such genes are differentially associated with specific chromosomes, suggesting chromosome specific regulatory roles in myogenesis. Rhabdomyosarcoma (RMS), a tumor of skeletal muscle, shares common features with normal muscle cells. We hypothesized that RMS and myogenic cells possess differences in chromosomal organization related to myogenic gene arrangement. We compared the organizational characteristics of chromosomes 2 and 18, chosen for their difference in myogenic gene arrangement, in cultured RMS cell lines and normal myoblasts and myotubes. We found chromosome-specific differences in organization during normal myogenesis, with increased area occupied and a shift in peripheral localization specifically for chromosome 2. Most strikingly, we found a differentiation-dependent difference in positioning of chromosome 2 relative to the nuclear axis, with preferential positioning along the major nuclear axis present only in myotubes. RMS cells demonstrated no preference for such axial positioning, but induced differentiation through transfection of the pro-myogenic miRNA miR-206 resulted in an increase of major axial positioning of chromosome 2. Our findings identify both a differentiation-dependent, chromosome-specific change in organization in normal myogenesis, and highlight the role of chromosomal spatial organization in myogenic differentiation.
In vitro and in vivo antioxidant therapeutic evaluation of phytochemicals from different parts of Dodonaea viscosa Jacq
Authors: Khan Siraj , Rehman Mujeeb Ur , Khan Muhammad Zafar Irshad , Kousar Rehana , Muhammad Khan , Haq Ihsan Ul , Ijaz Khan Muhammad , Almasoud Najla , Alomar Taghrid S. , Rauf Abdur
Published: November 2023

Introduction: Natural antioxidants are vital to promote health and treat critical disease conditions in the modern healthcare system. This work adds to the index of natural medicines by exploring the antioxidant potential of Dodonaea viscosa Jacq. (Plant-DV).

Material and Methods: The aqueous extract of leaves and flower-containing seeds from plant-DV in freshly prepared phosphate buffer is evaluated for antioxidant potential. In vitro antioxidant potential of the nascent and oxidatively stressed extracts was analyzed through glutathione (GSH) assay, hydrogen peroxide (H2O2) scavenging effect, glutathione-S-transferase (GST) assay, and catalase (CAT) activity. In vivo therapeutic assessment is performed in Wistar Albino rats using vitamin C as a positive control. The livers and kidneys of individual animals are probed for glutathione, glutathione-S-transferase, and catalase activities.

Results: flower-containing seeds have GSH contents (59.61 µM) and leaves (32.87 µM) in the fresh aqueous extracts. The hydrogen peroxide scavenging effect of leaves is superior to flower-containing seeds with 17.25% and 14.18% respectively after 30 min incubation. However, oxidatively stressed extracts with Ag(I) and Hg(II) show declining GSH and GST levels. The plant extracts are non-toxic in rats at 5000 mg/Kg body weight. Liver and kidneys homogenate reveal an increase in GSH, GST, and CAT levels after treatment with 150 ± 2 mg/kg and 300 ± 2 mg/kg body weight plant extract compared with normal saline-treated negative and vitamin C treated positive control.

Discussion: The crude aqueous extracts of leaves and flower-containing seeds of plant-DV show promising antioxidant potential both in in vitro and in vivo evaluation.
When may a system be referred to as complex?—an entropic perspective
Authors: Tsallis Constantino
Published: November 2023

Defining complexity is hard and far from unique—like defining beauty, intelligence, creativity, and many other such abstract concepts. In contrast, describing concrete complex systems is a sensibly simpler task. We focus here on such an issue from the perspective of entropic functionals, either additive or nonadditive. Indeed, for the systems currently referred to as simple, the statistical mechanics and associated (additive) entropy is that of Boltzmann–Gibbs, formulated 150 years ago. This formalism constitutes a pillar of contemporary theoretical physics and is typically grounded on strong chaos, mixing, ergodicity, and similar hypotheses, which typically emerge for systems with short-range space–time generic correlations. It fails, however, for the so-called complex systems, where generic long-range space–time correlations prevail, typically grounded on weak chaos. Many such nontrivial systems are satisfactorily handled within a generalization of the Boltzmann–Gibbs theory, namely, nonextensive statistical mechanics, introduced in 1988 and grounded on nonadditive entropies. Illustrations are presented in terms of D-dimensional simplexes such as nodes (D = 0), bonds (D = 1), plaquettes (D = 2), polyhedra (D = 3, …), and higher-order ones. A regularly updated bibliography is available at http://tsallis.cat.cbpf.br/biblio.htm.
3-dimensional intracardiac echocardiography for structural heart interventions
Authors: Ho Edwin C. , Assafin Manaf , Sugiura Tadahisa , Granada Juan F. , Chau Mei , Latib Azeem
Published: November 2023

New generation 3-dimensional matrix array intracardiac echocardiography catheters have become commercially available recently, increasing image plane options compared to 2-dimensional and older generation 3-dimensional intracardiac echocardiography catheters. They are beginning to play an important role in structural heart interventions, especially for transcatheter tricuspid interventions, due to advantages in some situations that increase image quality over transesophageal echocardiography.
Gender transformative approaches in mHealth for maternal healthcare in sub-Saharan Africa: a systematic review
Authors: Udenigwe Ogochukwu , Omonaiye Olumuyiwa , Yaya Sanni
Published: November 2023

Background

This review focuses on studies about digital health interventions in sub-Saharan Africa. Digital health interventions in sub-Saharan Africa are increasingly adopting gender-transformative approaches to address factors that derail women's access to maternal healthcare services. However, there remains a paucity of synthesized evidence on gender-transformative digital health programs for maternal healthcare and the corresponding research, program and policy implications. Therefore, this systematic review aims to synthesize evidence of approaches to transformative gender integration in digital health programs (specifically mHealth) for maternal health in sub-Saharan Africa.

Method

The following key terms “mobile health”, “gender”, “maternal health”, “sub-Saharan Africa” were used to conduct electronic searches in the following databases: PsycInfo, EMBASE, Medline (OVID), CINAHL, and Global Health databases. The method and results are reported as consistent with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Data synthesis followed a convergent approach for mixed-method systematic review recommended by the JBI (Joanna Briggs Institute).

Results

Of the 394 studies retrieved from the databases, 11 were included in the review. Out of these, six studies were qualitative in nature, three were randomized control trials, and two were mixed-method studies. Findings show that gender transformative programs addressed one or more of the following categories: (1) gender norms/roles/relations, (2) women's specific needs, (3) causes of gender-based health inequities, (4) ways to transform harmful gender norms, (5) promoting gender equality, (6) progressive changes in power relationships between women and men. The most common mHealth delivery system was text messages via short message service on mobile phones. The majority of mHealth programs for maternal healthcare were focused on reducing unintended pregnancies through the promotion of contraceptive use. The most employed gender transformative approach was a focus on women's specific needs.

Conclusion

Findings from gender transformative mHealth programs indicate positive results overall. Those reporting negative results indicated the need for a more explicit focus on gender in mHealth programs. Highlighting gender transformative approaches adds to discussions on how best to promote mHealth for maternal health through a gender transformative lens and provides evidence relevant to policy and research.

Systematic review registration

PROSPERO CRD42023346631.
The Power Rainbow: a tool to support 3rd–5th graders in analyzing systems of power
Authors: Mariën Hania K. , Kirby Anna L.
Published: November 2023

Drawing on scholars of critical theory and pedagogy, we understand power as operating within nested social systems, meaning that individuals experiencing injustice are impacted not only by the most immediate agent of that injustice but also by the broader institutions, policies, and values of their society. The practice of attending to power and how it shapes our societies at multiple levels (i.e.,power analysis) is necessary to critical research approaches, including Critical Participatory Action Research (CPAR). While adolescents and adults (the age groups most commonly engaging in CPAR) are likely to have developed some understanding of systems of power through experience, dialog, and/or educational experiences, children participating in CPAR have generally had fewer opportunities to develop this type of analysis. In our own CPAR projects with 3rd–5th grade children, we have witnessed the challenges and possibilities of exploring power with child CPAR team members. In this paper, we introduce a methodological tool that we developed to facilitate power analysis during critical research projects like these:The Power Rainbow.The Power Rainbowis a graphic representation of nested systems of power, which can be utilized with children in multiple ways throughout the CPAR process. The tool concretizes the abstract concept of systemic power through shape, color, and text, and scaffolds the type of structural thinking necessary to research and take action towards more just futures.
Causal relationship between breakfast skipping and bone mineral density: a two-sample Mendelian randomized study
Authors: Yu Jinsheng , Zhuang Chen , Guo Wenxuan , Zhou Xing , Chen Yixuan , Wang Likang , Li Wenkai , Zhu Yiwen , Zhuang Rujie , Tian Kun
Published: November 2023

Objective

To explore the causal association between breakfast skipping and bone mineral density (BMD) through two-sample Mendelian randomisation (MR) analysis.

Methods

A two-sample MR approach was adopted to explore the causal relationship of breakfast skipping with BMDs (across three skeletal sites and five age groups). Publicly available genome-wide association study summary data were used for MR analysis. We used five methods to estimate the causal associations between breakfast skipping and BMDs: inverse-variance weighting (IVW), MR-Egger, weighted median, simple mode, and weighted mode. IVW was used for the main analysis and the remaining four methods were used as supplementary analyses. The heterogeneity of the MR results was determined using IVW and MR-Egger methods. The pleiotropy of the MR results was determined using MR-Egger intercept. Furthermore, a leave-one-out test was performed to determine whether the MR results were affected by a single nucleotide polymorphism.

Results

With the IVW method, we did not find any causal relationship between breakfast skipping and forearm, femoral neck, and lumbar spine BMD. Subsequently, when we included BMD data stratified by five different age groups in the analysis, the results showed that there was no apparent causal effect between breakfast skipping and age-stratified BMD. This finding was supported by all four supplementary methods (P > 0.05 for all methods). No heterogeneity or horizontal pleiotropy was detected in any of the analyses (P > 0.05). The leave-one-out tests conducted in the analyses did not identify any single nucleotide polymorphism that could have influenced the MR results, indicating the reliability of our findings.

Conclusion

No causal effect was found between breakfast skipping and BMD (across three skeletal sites and five age groups).
Sea buckthorn, its bioactive constituents, and mechanism of action: potential application in female reproduction
Authors: Mihal Michal , Roychoudhury Shubhadeep , Sirotkin Alexander V. , Kolesarova Adriana
Published: November 2023

Sea buckthorn (Hippophae rhamnoides L.) is a flowering shrub, and its berries have been utilized for decades as a raw ingredient in cuisines and herbal remedies. This evidence-based study focuses on its key bioactive constituents, and mechanism of protective effects with a focus on female reproductive processes. Parts of the plant contain phenols, carotenoids (lycopene, carotene, lutein, and zeaxanthin), flavonoids (isorhamnetin, quercetin, glycosides, and kaempferol), tocopherols, sterols, polyunsaturated fatty acids, minerals, vitamins, omega 3, 6, 9 and rare omega 7 fatty acids etc. Key polyphenolic flavonoids such as isorhamnetin and quercetin are believed to be mainly responsible behind its health benefits (against cardiovascular diseases, metabolic syndrome, obesity etc.) through properties including anti-cancer, antioxidant, and anti-inflammatory activities. These sea buckthorn constituents appear to mediate healthy ovarian cell proliferation, death, and hormone release, as well as decrease ovarian cancer possibly through apoptosis, and hormonal (estrogen) release. Thus, sea buckthorn and its bioactive ingredients may have potential in the management of gynecological problems such as uterine inflammation, endometriosis, and easing symptoms of vulvovaginal atrophy in postmenopausal women (by targeting inflammatory cytokines and vascular endothelial growth factor – VEGF). Apigenin, myricetin, and luteolin have also been recommended as prospective ovarian cancer preventative and adjuvant therapy options as they can inhibit ovarian cancerogenesis by triggering apoptosis and halting the cell cycle in ovarian tumors. Furthermore, its oil (containing carotenoid, sterol, and hypericin) has been speculated as an alternative to estrogen replacement therapy for postmenopausal women particularly to improve vaginal epithelial integrity. However, it is uncertain whether steroid hormone receptors, reactive oxygen species (ROS), and inflammatory regulators are actually behind sea buckhorn’s actions. Sea buckthorn, and its compounds’ health promoting potential warrants further validation not just in vitro and in animal research, but also in clinical trials to identify and/or standardize optimal methods of delivery of biologically active molecules.
Effect of mechanical vibration on heat and mass transfer performance of pool boiling process in porous media: a literature review
Authors: Zhao Yuanyuan , Wu Hongqiang , Dang Chaobin
Published: November 2023

Pool boiling in porous media has been applied in various thermal management systems by using latent heat and increasing the heat transfer area and thermal conduction path to improve the heat transfer performance. In mechanical equipment, vibration is an inevitable problem due to reasons such as engine operation and high-speed relative motion between transmission system components, which causes the system components to be affected by vibration forces or vibration accelerations. This study focuses on a review of published articles about the effects of mechanical vibration on the characteristics of boiling process in porous media by two aspects: heat transfer performance and bubble dynamics. Heat transfer coefficient (HTC) and critical heat flux are two main parameters used to measure the boiling heat transfer characteristics of porous media. For bubble dynamics investigations, properties such as migration, fragment, coalescence, departure diameter and frequency are the focus of research attention. Different mechanical vibration parameters, i.e., direction, frequency, and amplitude, will have different effects on the above characteristics. It is worth mentioning that the greatest influence occurs under resonance conditions, and this has been verified through experimental and simulation calculations. This review highlights the importance of considering mechanical vibrations in the design and optimization of porous media systems for efficient heat transfer applications. Further research is warranted to explore the detailed mechanisms and optimize the vibration parameters for enhanced heat transfer performance in thermal management systems using porous media.
Assessing the impact of a waste incinerator on the environment using the MAIAC-AOD and AERMOD models
Authors: Hongthong Anuttara , Nakapan Supachai
Published: November 2023

The distribution and concentration of air pollutants from infectious waste incineration between 2019 and 2021 were examined in this study using an AERMOD model, including sulfur dioxide (SO2), nitrogen dioxide (NOx), and particulate matter (PM2.5). The MAIAC-AOD value at a 1 km resolution was used to develop a regression model with meteorological information for predicting PM2.5, which was then compared with the concentration from the AERMOD simulation. The following maximum 1-h, 24-h, and annual average concentrations of all pollutants were found to have occurred in 2019. The distribution of SO2 and NOx in 1 h was largest in 2020 at 1,000 m to the northwest, with concentrations of 37.68 and 93.99 μg/m3, respectively. The 24-h concentrations of SO2 and NOx were greatest in 2021 at 3.63 and 8.90 μg/m3, respectively, 720 m northeast of the stack. The annual concentrations of SO2 and NOx were highest in 2019 at 0.56 and 1.36 μg/m3, respectively. The highest annual PM2.5 concentration was 0.033 μg/m3, 730 m to the northeast in 2019. The predicted PM2.5 using MAIAC-AOD correlated with the simulated value from AERMOD, with R2 values of 0.7630, 0.7607, and 0.6504 for 2019, 2020, and 2021, respectively, which were higher closer to the stack than outside. As a result, investigations into the distribution of air pollution should benefit from the integration of air modeling and satellite information.
Hepatocyte-specific regulation of autophagy and inflammasome activation via MyD88 during lethal Ehrlichia infection
Authors: Teymournejad Omid , Sharma Aditya Kumar , Abdelwahed Mohammed , Kader Muhamuda , Ahmed Ibrahim , Elkafas Hoda , Ismail Nahed
Published: November 2023

Hepatocytes play a crucial role in host response to infection. Ehrlichia is an obligate intracellular bacterium that causes potentially life-threatening human monocytic ehrlichiosis (HME) characterized by an initial liver injury followed by sepsis and multi-organ failure. We previously showed that infection with highly virulent Ehrlichia japonica (E. japonica) induces liver damage and fatal ehrlichiosis in mice via deleterious MyD88-dependent activation of CASP11 and inhibition of autophagy in macrophage. While macrophages are major target cells for Ehrlichia, the role of hepatocytes (HCs) in ehrlichiosis remains unclear. We investigated here the role of MyD88 signaling in HCs during infection with E. japonica using primary cells from wild-type (WT) and MyD88-/- mice, along with pharmacologic inhibitors of MyD88 in a murine HC cell line. Similar to macrophages, MyD88 signaling in infected HCs led to deleterious CASP11 activation, cleavage of Gasdermin D, secretion of high mobility group box 1, IL-6 production, and inflammatory cell death, while controlling bacterial replication. Unlike macrophages, MyD88 signaling in Ehrlichia-infected HCs attenuated CASP1 activation but activated CASP3. Mechanistically, active CASP1/canonical inflammasome pathway negatively regulated the activation of CASP3 in infected MyD88-/- HCs. Further, MyD88 promoted autophagy induction in HCs, which was surprisingly associated with the activation of the mammalian target of rapamycin complex 1 (mTORC1), a known negative regulator of autophagy. Pharmacologic blocking mTORC1 activation in E. japonica-infected WT, but not infected MyD88-/- HCs, resulted in significant induction of autophagy, suggesting that MyD88 promotes autophagy during Ehrlichia infection not only in an mTORC1-indpenedent manner, but also abrogates mTORC1-mediated inhibition of autophagy in HCs. In conclusion, this study demonstrates that hepatocyte-specific regulation of autophagy and inflammasome pathway via MyD88 is distinct than MyD88 signaling in macrophages during fatal ehrlichiosis. Understanding hepatocyte-specific signaling is critical for the development of new therapeutics against liver-targeting pathogens such as Ehrlichia.
Association of nicotine dependence and gut microbiota: a bidirectional two-sample Mendelian randomization study
Authors: Chen Yuexuan , Zhao Mengjiao , Ji Kaisong , Li Jingjing , Wang Shuxin , Lu Liming , Chen Zhenhu , Zeng Jingchun
Published: November 2023

Background

Nicotine dependence is a key factor influencing the diversity of gut microbiota, and targeting gut microbiota may become a new approach for the prevention and treatment of nicotine dependence. However, the causal relationship between the two is still unclear. This study aims to investigate the causal relationship between nicotine dependence and gut microbiota.

Methods

A two-sample bidirectional Mendelian randomization (MR) study was conducted using the largest existing gut microbiota and nicotine dependence genome-wide association studies (GWAS). Causal relationships between genetically predicted nicotine dependence and gut microbiota abundance were examined using inverse variance weighted, MR-Egger, weighted median, simple mode, weighted mode, and MR-PRESSO approaches. Cochrane’s Q test, MR-Egger intercept test, and leave-one-out analysis were performed as sensitivity analyses to assess the robustness of the results. Multivariable Mendelian randomization analysis was also conducted to eliminate the interference of smoking-related phenotypes. Reverse Mendelian randomization analysis was then performed to determine the causal relationship between genetically predicted gut microbiota abundance and nicotine dependence.

Results

Genetically predicted nicotine dependence had a causal effect on Christensenellaceae (β: -0.52, 95% CI: -0.934–0.106, P = 0.014). The Eubacterium xylanophilum group (OR: 1.106, 95% CI: 1.004-1.218), Lachnoclostridium (OR: 1.118, 95% CI: 1.001-1.249) and Holdemania (OR: 1.08, 95% CI: 1.001-1.167) were risk factors for nicotine dependence. Peptostreptococcaceae (OR: 0.905, 95% CI: 0.837-0.977), Desulfovibrio (OR: 0.014, 95% CI: 0.819-0.977), Dorea (OR: 0.841, 95% CI. 0.731-0.968), Faecalibacterium (OR: 0.831, 95% CI: 0.735-0.939) and Sutterella (OR: 0.838, 95% CI: 0.739-0.951) were protective factor for nicotine dependence. The sensitivity analysis showed consistent results.

Conclusion

The Mendelian randomization study confirmed the causal link between genetically predicted risk of nicotine dependence and genetically predicted abundance of gut microbiota. Gut microbiota may serve as a biomarker and offer insights for addressing nicotine dependence.
SARS-CoV-2 testing in the Slovak Republic from March 2020 to September 2022 – summary of the pandemic trends
Authors: Janostiakova Nikola , Gnip Andrej , Kodada Dominik , Saade Rami , Blandova Gabriela , Mikova Emilia , Tibenska Elena , Repiska Vanda , Minarik Gabriel
Published: November 2023

The COVID-19 pandemic has been part of Slovakia since March 2020. Intensive laboratory testing ended in October 2022, when the number of tests dropped significantly, but the state of the pandemic continues to this day. For the management of COVID-19, it is important to find an indicator that can predict pandemic changes in the community. The average daily/weekly Ct value with a certain time delay can predict changes in the number of cases of SARS-CoV-2 infection, which can be a useful indicator for the healthcare system. The study analyzed the results of 1,420,572 RT-qPCR tests provided by one accredited laboratory during the ongoing pandemic in Slovakia from March 2020 to September 2022. The total positivity of the analyzed tests was 24.64%. The average Ct values found were the highest in the age group of 3–5 years, equal to the number 30.75; the lowest were in the age group >65 years, equal to the number 27. The average weekly Ct values ranged from 22.33 (pandemic wave week) to 30.12 (summer week). We have summarized the results of SARS-CoV-2 diagnostic testing in Slovakia with the scope defined by the rate and positivity of tests carried out at Medirex a.s. laboratories.
Does postoperative pulmonary infection correlate with intestinal flora following gastric cancer surgery? — a nested case–control study
Authors: Yang Jie , He Yuhua , Liao Xi , Hu Jiankun , Li Ka
Published: November 2023

Introduction

The primary objective of this study was to investigate the potential correlation between gut microbes and postoperative pulmonary infection in gastric cancer patients. Additionally, we aimed to deduce the mechanism of differential functional genes in disease progression to gain a better understanding of the underlying pathophysiology.

Methods

A nested case–control study design was utilized to enroll patients with gastric cancer scheduled for surgery at West China Hospital of Sichuan University. Patients were categorized into two groups, namely, the pulmonary infection group and the control group, based on the development of postoperative pulmonary infection. Both groups were subjected to identical perioperative management protocols. Fecal samples were collected 24 h postoperatively and upon pulmonary infection diagnosis, along with matched controls. The collected samples were subjected to 16S rDNA and metagenomic analyses, and clinical data and blood samples were obtained for further analysis.

Results

A total of 180 fecal specimens were collected from 30 patients in both the pulmonary infection and control groups for 16S rDNA analysis, and 3 fecal samples from each group were selected for metagenomic analysis. The study revealed significant alterations in the functional genes of the intestinal microbiome in patients with postoperative pulmonary infection in gastric cancer, primarily involving Klebsiella, Enterobacter, Ruminococcus, and Collinsella. During postoperative pulmonary infection, gut flora and inflammatory factors were found to be associated with the lipopolysaccharide synthesis pathway and short-chain fatty acid (SCFA) synthesis pathway.

Discussion

The study identified enriched populations of Klebsiella, Escherella, and intestinal bacteria during pulmonary infection following gastric cancer surgery. These bacteria were found to regulate the lipopolysaccharide synthesis pathway, contributing to the initiation and progression of pulmonary infections. Inflammation modulation in patients with postoperative pulmonary infection may be mediated by short-chain fatty acids. The study also revealed that SCFA synthesis pathways were disrupted, affecting inflammation-related immunosuppression pathways. By controlling and maintaining intestinal barrier function, SCFAs may potentially reduce the occurrence of pulmonary infections after gastric cancer surgery. These findings suggest that targeting the gut microbiome and SCFA synthesis pathways may be a promising approach for preventing postoperative pulmonary infections in gastric cancer patients.
Unraveling the transcriptomic signatures of Parkinson’s disease and major depression using single-cell and bulk data
Authors: Christodoulou Christiana C. , Onisiforou Anna , Zanos Panos , Papanicolaou Eleni Zamba
Published: November 2023

Background

Motor symptoms are well-characterized in Parkinson’s disease (PD). However, non-motor symptoms, such as depression, are commonly observed and can appear up to 10 years before motor features, resulting in one-third of individuals being misdiagnosed with a neuropsychiatric disorder. Thus, identifying diagnostic biomarkers is crucial for accurate PD diagnosis during its prodromal or early stages.

Methods

We employed an integrative approach, combining single nucleus RNA and bulk mRNA transcriptomics to perform comparative molecular signatures analysis between PD and major depressive disorder (MDD). We examined 39,834 nuclei from PD (GSE202210) and 32,707 nuclei from MDD (GSE144136) in the dorsolateral prefrontal cortex (dlPFC) of Brodmann area 9. Additionally, we analyzed bulk mRNA peripheral blood samples from PD compared to controls (GSE49126, GSE72267), as well as MDD compared to controls (GSE39653).

Results

Our findings show a higher proportion of astrocytes, and oligodendrocyte cells in the dlPFC of individuals with PD vs. MDD. The excitatory to inhibitory neurons (E/I) ratio analysis indicates that MDD has a ratio close to normal 80/20, while PD has a ratio of 62/38, indicating increased inhibition in the dlPFC. Microglia displayed the most pronounced differences in gene expression profiles between the two conditions. In PD, microglia display a pro-inflammatory phenotype, while in MDD, they regulate synaptic transmission through oligodendrocyte-microglia crosstalk. Analysis of bulk mRNA blood samples revealed that the COL5A, MID1, ZNF148, and CD22 genes were highly expressed in PD, whereas the DENR and RNU1G2 genes were highly expressed in MDD. CD22 is involved in B-cell activation and the negative regulation of B-cell receptor signaling. Additionally, CD86, which provides co-stimulatory signals for T-cell activation and survival, was found to be a commonly differentially expressed gene in both conditions. Pathway analysis revealed several immune-related pathways common in both conditions, including the complement and coagulation cascade, and B-cell receptor signaling.

Discussion

This study demonstrates that bulk peripheral immune cells play a role in both conditions, but neuroinflammation in the dlPFC specifically manifests in PD as evidenced by the analysis of single nucleus dlPFC datasets. Integrating these two omics levels offers a better understanding of the shared and distinct molecular pathophysiology of PD and MDD in both the periphery and the brain. These findings could lead to potential diagnostic biomarkers, improving accuracy and guiding pharmacological treatments.
Early versus delayed computed tomography-guided celiac plexus neurolysis for palliative pain management in patients with advanced pancreatic cancer: a retrospective cohort study
Authors: Lu Fan , Wang Xiaojia , Tian Jie , Li Xuehan
Published: November 2023

Introduction

Abdominal and back pain is the most frequent symptom in patients with pancreatic cancer, with pain management being extremely challenging. This study aimed to evaluate pain control, opioid consumption, pain-interfered quality of life, and survival after early and delayed computed tomography (CT)-guided celiac plexus neurolysis (CPN).

Methods

A retrospective analysis of pancreatic cancer patients receiving CPN for pain (n = 56) between June 2018 and June 2021 was done. The patients were grouped as early group (n = 22) and delayed group (n = 34) on the basis of the presence of persistent refractory pain according to expert consensus on refractory cancer pain.

Results

Both groups were comparable in demographic characteristics and baseline pain conditions measured using the numeric rating scale (5.77 ± 1.23 vs. 6.27 ± 1.21; p = 0.141). The pain scores were significantly reduced in both groups; early CPN resulted in significantly lower scores from 3 to 5 months. The opioid consumption gradually decreased to a minimum at 2 weeks but increased at 1 month (35.56 ± 30.14 mg and 50.48 ± 47.90 mg, respectively); significantly larger consumption from 2 to 4 months was seen in the delayed group. The total pain interference was lower than baseline in all patients, with significant improvement after early CPN in sleep, appetite, enjoyment of life, and mood. The average survival time of the two groups was comparable.

Conclusion

Early application of CT-guided CPN for patients with advanced pancreatic cancer may help reduce pain exacerbation and opioids consumption, without influencing the survival.
Tumor suppressive miR-99b-5p as an epigenomic regulator mediating mTOR/AR/SMARCD1 signaling axis in aggressive prostate cancer
Authors: Waseem Mohammad , Gujrati Himali , Wang Bi-Dar
Published: November 2023

Introduction

African American (AA) men exhibited 2.3-fold higher PCa incidence and 1.7-fold higher PCa mortality rates when compared to the European American (EA) men. Besides the socioeconomic factors, emerging evidence has highlighted that biological risk factors may play critical roles in the AA PCa disparities. Previously, we have shown that downregulated miR-99b-5p and upregulated mTOR cooperatively promotes the AA PCa aggressiveness and drug resistance.

Methods

In this study, we aimed to explore the miR-99b-5p/mTOR/AR/SMARCD1 signaling axis in AA PCa aggressiveness. The analyses used in the study included immunofluorescence, western blot, in-vitro functional assays (TUNEL, colony forming, and MTT), and chromatin immunoprecipitation (ChIP)-qPCR assays in 2D and/or 3D culture model of EA PCa and AA PCa cell lines.

Results

Specifically, the immunofluorescence staining, and western blot analysis has revealed that nuclear mTOR, AR, and SMARCD1 were highly expressed in AA PCa (MDA PCa 2b) compared to EA PCa (LNCaP) cell line. Western blot analysis further revealed that miR-99b-5p inhibited protein levels of mTOR, AR/AR-V7 and SMARCD1 in cytoplasm and nuclei of EA and AA PCa. The in-vitro functional (MTT, TUNEL, and clonogenic) assays have demonstrated that miR-99b-5p effectively inhibited cell proliferation/survival and induced cell apoptosis in EA and AA PCa cells. Moreover, combination of miR-99b-5p and enzalutamide (Enz) synergistically enhances the cytotoxicity against aggressive AA PCa and castration-resistant prostate cancer (CRPC). mTOR ChIP-qPCR assays further demonstrated that miR-99b-5p or miR-99b-5p/Enz significantly reduces the recruitment of mTOR to the genes involved in the metabolic reprogramming in CRPC.

Discussion

Taken together, miR-99b-5p may function as an epigenomic driver to modulate the mTOR/AR/SMARCD1 signaling axis in AA PCa and resistant CRPC.
Stereotactic body radiotherapy with CyberKnife® System for low- and intermediate-risk prostate cancer: clinical outcomes and toxicities of CyPro Trial
Authors: Borzillo Valentina , Scipilliti Esmeralda , Pezzulla Donato , Serra Marcello , Ametrano Gianluca , Quarto Giuseppe , Perdonà Sisto , Rossetti Sabrina , Pignata Sandro , Crispo Anna , Di Gennaro Piergiacomo , D’Alesio Valentina , Arrichiello Cecilia , Buonanno Francesca , Mercogliano Simona , Russo Antonio , Tufano Antonio , Di Franco Rossella , Muto Paolo
Published: November 2023

Simple summary

Stereotactic body radiotherapy (SBRT) of 35–36.25 Gy in five fractions with the CyberKnife System yields excellent control with low toxicity in low–intermediate-risk prostate cancer patients. We found no differences in biochemical control and overall survival in relation to dose. There were no significant differences in toxicity or quality of life between the two groups.

Aims

Stereotactic body radiotherapy (SBRT) is an emerging therapeutic approach for low- and intermediate-risk prostate cancer. We present retrospective data on biochemical control, toxicity, and quality of life of CyPro Trial.

Materials and methods

A total of 122 patients with low- and intermediate-risk prostate cancer were treated with the CyberKnife System at a dose of 35 Gy or 36.25 Gy in five fractions. Biochemical failure (BF)/biochemical disease-free survival (bDFS) was defined using the Phoenix method (nadir + 2 ng/ml). Acute/late rectal and urinary toxicities were assessed by the Radiation Therapy Oncology Group (RTOG) toxicity scale. Quality of life (QoL) was assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C30 and PR25. International Erectile Function Index-5 (IIEF5) and International Prostate Symptom Score (IPSS) questionnaires were administered at baseline, every 3 months after treatment during the first years, and then at 24 months and 36 months.

Results

The 1-, 2-, and 5-year DFS rates were 92.9%, 92.9%, and 92.3%, respectively, while the 1-, 2-, and 5-year bDFS rates were 100%, 100%, and 95.7%, respectively. With regard to risk groups or doses, no statistically significant differences were found in terms of DFS or bDFS. Grade 2 urinary toxicity was acute in 10% and delayed in 2% of patients. No Grade 3 acute and late urinary toxicity was observed. Grade 2 rectal toxicity was acute in 8% and late in 1% of patients. No Grade 3–4 acute and late rectal toxicity was observed. Grade 2 acute toxicity appeared higher in the high-dose group (20% in the 36.25-Gy group versus 3% in the 35-Gy group) but was not statistically significant.

Conclusion

Our study confirms that SBRT of 35–36.25 Gy in five fractions with the CyberKnife System produces excellent control with low toxicity in patients with low–intermediate-risk prostate cancer. We found no dose-related differences in biochemical control and overall survival. Further confirmation of these results is awaited through the prospective phase of this study, which is still ongoing.
Refractory celiac disease and its mimickers: a review on pathogenesis, clinical-pathological features and therapeutic challenges
Authors: Scarmozzino Federico , Pizzi Marco , Pelizzaro Filippo , Angerilli Valentina , Dei Tos Angelo Paolo , Piazza Francesco , Savarino Edoardo Vincenzo , Zingone Fabiana , Fassan Matteo
Published: November 2023

Refractory celiac disease (RCD) and enteropathy-associated T-cell lymphoma (EATL) are rare, yet severe complications of celiac disease (CD). Over the last decades, several studies have addressed the biology and clinical-pathological features of such conditions, highlighting unique disease patterns and recurrent genetic events. Current classification proposals identify two forms of RCD, namely: (i) type 1 RCD (RCD-I), characterized by phenotypically normal intra-epithelial lymphocytes (IELs); and (ii) type 2 RCD (RCD-II), featuring phenotypically aberrant IELs. While RCD-I likely represents a gluten-independent dysimmune reaction against small bowel epithelial cells, RCD-II is better considered an in situ aggressive T-cell lymphoma, with high rates of progression to overt EATL. The diagnosis of RCD and EATL is often challenging, due to misleading clinical-pathological features and to significant overlap with several CD-unrelated gastro-intestinal disorders. Similarly, the treatment of RCD and EATL is an unmet clinical need for both gastroenterologists and hematologists. Moving from such premises, this review aims to provide a comprehensive view of RCD and EATL, specifically considering their pathogenesis and the many still open issues concerning their diagnosis and clinical management.
Chinese herbal medicine and active ingredients for diabetic cardiomyopathy: molecular mechanisms regulating endoplasmic reticulum stress
Authors: Ao Lianjun , Chen Zhengtao , Yin Jiacheng , Leng Yulin , Luo Yue , Fu Xiaoxu , Liu Hanyu , Liu Xiaoke , Gao Hong , Xie Chunguang
Published: November 2023

Abstract Background: Diabetic cardiomyopathy (DCM) is one of the serious microvascular complications of diabetes mellitus. It is often associated with clinical manifestations such as arrhythmias and heart failure, and significantly reduces the quality of life and years of survival of patients. Endoplasmic reticulum stress (ERS) is the removal of unfolded and misfolded proteins and is an important mechanism for the maintenance of cellular homeostasis. ERS plays an important role in the pathogenesis of DCM by causing cardiomyocyte apoptosis, insulin resistance, calcium imbalance, myocardial hypertrophy and fibrosis. Targeting ERS is a new direction in the treatment of DCM. A large number of studies have shown that Chinese herbal medicine and active ingredients can significantly improve the clinical outcome of DCM patients through intervention in ERS and effects on myocardial structure and function, which has become one of the hot research directions.

Purpose: The aim of this review is to elucidate and summarize the roles and mechanisms of Chinese herbal medicine and active ingredients that have the potential to modulate endoplasmic reticulum stress, thereby contributing to better management of DCM.

Methods: Databases such as PubMed, Web of Science, China National Knowledge Internet, and Wanfang Data Knowledge Service Platform were used to search, analyze, and collect literature, in order to review the mechanisms by which phytochemicals inhibit the progression of DCM by targeting the ERS and its key signaling pathways. Keywords used included “diabetic cardiomyopathy” and “endoplasmic reticulum stress.”

Results: This review found that Chinese herbs and their active ingredients can regulate ERS through IRE1, ATF6, and PERK pathways to reduce cardiomyocyte apoptosis, ameliorate myocardial fibrosis, and attenuate myocardial hypertrophy for the treatment of DCM.

Conclusion: A comprehensive source of information on potential ERS inhibitors is provided in this review. The analysis of the literature suggests that Chinese herbal medicine and its active ingredients can be used as potential drug candidates for the treatment of DCM. In short, we cannot ignore the role of traditional Chinese medicine in regulating ERS and treating DCM, and look forward to more research and new drugs to come.
Shared parenting and father involvement after divorce in Denmark
Authors: Sandberg Kristian
Published: November 2023

The Scandinavian countries make interesting samples for the study of shared parenting as they are characterized by some of the highest levels of father involvement and gender equality globally. Despite numerous studies, data from Denmark is noticeably absent in the international debate, partly due to a researcher preference for publishing in Danish. Here, I present an overview of the increase in father involvement in Denmark since the 1960s and on the increase in shared parenting across recent decades. I further examine Danish law, ministerial guidelines and guidelines from major Danish public and private institutions/organizations involved in deciding or advising on parenting practices post-divorce. I relate these to international research findings as well as to findings from Danish research. Overall, I find that Danish guidelines/practice have several reservations against shared parenting and substantial father involvement, which are not considered warranted by a substantial number of scientists and which are not supported by the majority of the available evidence. It thus appears that societal transition toward increased shared parenting has happened on a largely voluntary basis in spite of official law/practice. Updated law and/or ministerial guidelines are likely necessary if politicians desire that children experience the same high degree of father involvement post-divorce that they experience in society in general.
Digital health care service reform and health inequity for older people: a quasi-natural experiment in China
Authors: Qi Xinzhu , Feng Tieying , Deng Renyi
Published: November 2023

Objective

Addressing health inequity (HI) for older people is a pivotal global public health concern, as it impedes the process of healthy ageing. The digital health care service reform (DHSR) emerges as a progressive public health approach to enhance the health and well-being of older adults by providing comprehensive and equitable medical services. This study elucidates the association between DHSR and HI for older individuals to augment comprehension of DHSR implementation.

Methods

The initiation of the action plan for smart health and eldercare (SHE) in 2017 serves as a quasi-natural experiment. Utilizing data from the China Health and Retirement Longitudinal Study (CHARLS) in 2015 and 2018, a propensity score matching (PSM) method was used to select samples, and a difference-in-differences (DID) regression was used to ascertain the net effect of DHSR on HI for older individuals in China. This methodology mitigates selection bias and segregates the DHSR effect from temporal shifts or other occurrences.

Results

The PSM-DID analysis reveals that DHSR reduced the HI index for older individuals by 0.301 (p < 0.01). Heterogeneity analyses indicate that the effect of DHSR was more pronounced in older males (−0.333, p < 0.01) than females (−0.251, p < 0.05). The impact of DHSR was notably higher for older population in the western (−0.557, p < 0.01) and central regions (−0.318, p < 0.05) compared to the eastern region, where the relationship was statistically non-significant.

Conclusion

The results demonstrate that DHSR plays a vital role in diminishing HI, fostering inclusive growth in public health. The study underscores the imperative of sustained DHSR endeavours and allocating resources to key older demographics to substantially mitigate HI.