bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards an integrated approach for understanding glia in Amyotrophic Lateral Sclerosis
Authors: Majewski Stanislaw , Klein Pierre , Boillée Séverine , Clarke Benjamin E. , Patani Rickie
Published: September 2024

Substantial advances in technology are permitting a high resolution understanding of the salience of glia, and have helped us to transcend decades of predominantly neuron‐centric research. In particular, recent advances in ‘omic’ technologies have enabled unique insights into glial biology, shedding light on the cellular and molecular aspects of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Here, we review studies using omic techniques to attempt to understand the role of glia in ALS across different model systems and post mortem tissue. We also address caveats that should be considered when interpreting such studies, and how some of these may be mitigated through either using a multi‐omic approach and/or careful low throughput, high fidelity orthogonal validation with particular emphasis on functional validation. Finally, we consider emerging technologies and their potential relevance in deepening our understanding of glia in ALS.
Externality and policy intervention in interregional travel with infectious diseases
Authors: Doi Naoshi , Yamazaki Shingo
Published: September 2024

This paper theoretically investigates externalities and policy interventions in travel during a pandemic. We develop a tractable static model of two regions from a short‐run perspective. The model shows that the externalities can be both negative and positive, depending on regional asymmetry. Thus, even when infectious diseases are widespread, travel restrictions do not necessarily reduce infections and do not necessarily improve social welfare. A formula for the optimal policy intervention is derived and shown to be the weighted average of four types of externalities defined by the direction of travel and the epidemiological status of a traveler.
Factors associated with systemic inflammatory response syndrome negativity at the early stage of sepsis among nonsurviving sepsis patients in intensive care unit
Authors: Fu Chunyi , Luo Jingchao , Wang Xiaogang , Xu Yuan , Liu Taotao
Published: September 2024

Objectives

This study aims to investigate the factors associated with systemic inflammatory response syndrome (SIRS) negativity during the early stage of sepsis in deceased septic patients.

Methods

Adult septic patients were included from the Medical Information Mart for Intensive Care IV (MIMIC‐IV) database between 2008 and 2019. Patients who did not survive after 28 days were assigned to the SIRS‐negative or SIRS‐positive group according to whether the SIRS score was less than two points within 24 h of intensive care unit admission. Logistic regression and a restricted cubic spline model were used to analyze factors and dose–response relationships.

Results

A total of 53,150 patients were screened in the MIMIC‐IV database, and 2706 sepsis nonsurvivors were ultimately included, 101 of whom were negative for SIRS. There were significant differences in sequential organ failure assessment (SOFA) scores between groups (8.18 ± 3.58 vs. 9.75 ± 4.28, p < 0.001). Logistic regression analysis indicated that lactate (odds ratio [OR] = 0.75 [95% CI = 0.62–0.90], p = 0.002), SOFA score (OR = 0.93 [95% CI = 0.87–1.00], p = 0.046), and age (OR = 1.04 [95% CI = 0.88–1.15], p = 0.012) were independent factors related to SIRS negativity in septic patients. Analysis with a restricted cubic spline model showed that the OR of SIRS negativity continued to increase with age, particularly for those over 80 years old (p for nonlinearity = 0.024). The OR of SIRS negativity was more than 1 when the SOFA score was <4 (p for nonlinearity = 0.149) and when the lactate was <1 (p for nonlinearity = 0.014).

Conclusions

For sepsis patients with poor prognoses, elderly individuals are more likely to be SIRS negative when they have mild organ dysfunction damage or mild tissue hypoperfusion in the early stage of sepsis. This warranted an opportunity to provide early diagnosis for elderly population with negative SIRS score in order to prevent poor outcomes.
Waiting for surgery after hip fracture—Health and/or economic risk?
Authors: Saxer Franziska , Hatz Christoph , Vach Werner ,   the PROFI Study Group
Published: September 2024

Objectives

Waiting for surgery is a disconcerting experience. It can have a negative impact on patients' outcomes and length of stay (LOS) as driver for treatment costs. Process‐optimisation may be a strategy to improve quality and cost‐efficacy. The study investigates the correlation between waiting for hip fracture surgery and patient characteristics, organisational variables, outcomes, LOS, and the distribution of waiting times and LOS over time, including cost estimates. Thereby the study aims to identify the potential for organisational improvements with respect to managing the waiting time.

Methods

Ten‐year routine health data (patient characteristics and follow‐up information) and process‐indicators that is, waiting time and LOS from a Swiss trauma‐centre were analysed retrospectively. Cost‐estimates were calculated based on Swiss diagnosis related groups and daily costs to evaluate hospital revenues.

Results

In total, 2572 patients aged ≥60 years with low‐energy hip fractures were included. Waiting times >48 h were associated with sub‐optimal outcomes. Over the years long waiting times decreased. This reduction was not reflected by a reduction in LOS which remained stable around 10 days, primarily driven by late discharge to in‐patient rehabilitation. Reimbursement persisted at an average revenue in the low 4–5‐digit range, depending on implant costs.

Conclusions

While there has been a reduction of waiting times, this has not translated into a reduction of LOS or potential savings in health care costs, due to the various dependencies along the patient journey. Managing waiting times may be an area for improvement, increasing cost‐efficacy, especially since long waiting times are still associated with inferior outcomes and LOS.
Patient and care partner perspectives and preferences related to myasthenia gravis treatment: A qualitative study
Authors: Yung Margaret , Narayanaswami Pushpa , Pesa Jacqueline , Choudhry Zia , Jackson Louis , Deering Kathleen L. , Sebaaly Jamie , Richardson Jordan , Feldman Josh , Peters Wesley , Taylor Melina , Foss Allison , West Bruce , Shea Lisa , Geonnotti Gabrielle , Govindarajan Raghav
Published: September 2024

Background and Aims

Due to the high symptom and treatment burden in myasthenia gravis (MG), understanding patient and care partner perspectives and preferences is crucial.

Methods

This study used voice analysis and virtual focus groups to understand patient and care partner experiences with MG‐related symptoms, treatments, and preferences. The voice analysis via social media listening used artificial intelligence‐powered tools to gather and structure public digital conversations on MG. Focus groups included people living with MG and care partners who completed a questionnaire and participated in a 1‐h virtual session facilitated using a semi‐structured interview guide. Qualitative data were aggregated, transcribed, and thematically analyzed.

Results

The voice analysis examined 11,554 posts from 8321 individuals, discussing MG symptoms, treatments, and burden. Of 7563 symptom‐related posts, 5902 (78%) conveyed negative, 1427 (19%) neutral, and 234 (3%) positive sentiment. The most frequently mentioned symptoms were categorized as dysarthria, muscle weakness, and dysphagia. MG treatment sentiment analysis identified 6667 posts (67%) as neutral, 2887 (29%) as negative, and 350 (4%) as positive. For the focus groups, 15 individuals (12 patients and 3 care partners) completed the questionnaire and 14 participated in the virtual focus group sessions. The 15 participants who completed the questionnaire prioritized treatment convenience, symptom control for improved quality of life, and preventing potential MG crises in their current treatment. New treatment expectations included increased effectiveness, less frequent dosing, faster onset, and fewer side effects. Participants were also receptive to wearable medication delivery systems placed on the body and valued direct involvement in treatment decisions.

Conclusion

Patients and care partners are often negatively impacted by MG symptoms and value convenient and fast‐acting treatments that control symptoms with minimal side effects. Considering patient preferences may help optimize treatment decisions and improve patients' overall well‐being and satisfaction in their care.
Effect of noninertial acceleration on heat transfer by Rayleigh–Bénard magnetoconvection: Exploring nonlinear dynamics
Authors: Aruna A. S. , Kavitha N.
Published: September 2024

Buoyancy‐driven Rayleigh–Bénard convection in the presence of a magnetic field, rotation, and temperature‐dependent viscosity has applications in the field of crystal growth, space laboratory experiments, and atmospheric convection. It also has potential applications in heat transfer and magnetohydrodynamics, which can occur in planetary and stellar interiors. The present work aims to study the combined effect of magnetic fields and rotation on the onset of Rayleigh–Bénard convection in temperature‐dependent viscosity Newtonian liquids with internal heat sources/sinks. Both linear and weak nonlinear stability analyses of convection are performed in the problem. The minimal representation of the Fourier series for the stream function and the magnetic potential allows us to derive the analytical expression for the thermal Rayleigh number () and the generalized Lorenz model. In linear theory, the critical Rayleigh number and the wave number are tabulated for different values of the Chandrasekhar number (), the Taylor number (), and the thermorheological parameter (), and the onset of stability is analyzed. It is found that the instability manifests at when for stress‐free and isothermal boundaries. In nonlinear theory, the generalized Lorenz model obtained is not amenable to analytical treatment; therefore, the classical fourth‐order Runge–Kutta method is applied to solve the Lorenz model. It is found that the internal Rayleigh number, the thermorheological parameter, and the Taylor number influence the onset of convection and heat transfer coefficient. It is also demonstrated that the joint increase in rotational force and magnetic field strength stabilizes the system strongly, thereby reducing heat transfer. However, increasing the heat source and the variable viscosity parameter have antagonistic influences.
Ascorbyl palmitate/hydroxypropyl‐β‐cyclodextrin inclusion complex loaded nanofibrous membrane for accelerated diabetic wound healing
Authors: Zhao Dan , Liu Jingchong , Liu Guotao , Hou Liangxuan , Zhou Liping , Wang Changtao , Wen Yongqiang
Published: September 2024

Reactive oxygen species (ROS) accumulation in chronic skin wounds impedes the healing process, thus it is necessary to eliminate the ROS from the vicinity of the wound in time. Ascorbyl palmitate (AP) is a potent antioxidant that suffers from solubility constraints, which largely limits its application. This study aims to improve AP's solubility by encapsulating it within 2‐hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) to acquire AP/CD inclusion complex (IC). This advancement facilitates the development of antioxidant and antibacterial nanofibrous membranes via electrospinning, utilizing polyvinyl alcohol (PVA) and quaternary ammonium chitosan (QCS). The developed PVA/QCS combined with AP/CD‐IC (PVA/QCS‐IC) nanofibers increase the release of AP, boasting good antioxidant property. In comparison to the PVA/QCS combined with AP counterparts (PVA/QCS‐AP), where AP is not encapsulated in HP‐β‐CD, the PVA/QCS‐IC nanofibers provide notable protection against oxidative stress in human skin fibroblasts and increased Col‐I expression levels. Additionally, the PVA/QCS‐IC nanofibers are able to suppress the growth of E. coli, S. aureus, and P. aeruginosa. Furthermore, the PVA/QCS‐IC nanofibers could effectively promote diabetic wound healing, facilitate collagen deposition, and reduce skin inflammation response when applied as a wound dressing in diabetic mice. The results suggest that the PVA/QCS‐IC nanofibers represent a promising solution for both enhancing AP solubility and its therapeutic potential, positioning them as potential candidates for diabetic wound care applications.
The risk of treatment‐related toxicities with PD‐1/PD‐L1 inhibitors in patients with lung cancer
Authors: Hu Hao , Zhu Qian , Tang Hua , Zhang Si‐Cai , Huang Yan‐Ze , Wang Ya‐Fang , Xu Zhi‐Yong , Yang Xiong‐Wen , Zheng Ji‐Hua , Guo Chang‐Ying
Published: September 2024

The risk of treatment‐related toxicities with programmed cell death 1 and its ligand (PD‐1/PD‐L1) inhibitors in patients with lung cancer is unclear and inconclusive. PubMed, EMBASE, and the Cochrane Library databases were systematically searched without language restrictions from inception to May 31, 2024 to identify Phase 3 randomized controlled trials of lung cancer comparing PD‐1/PD‐L1 inhibitors versus placebo/best supportive care (alone or in combination with nontargeted chemotherapy) that had available data regarding treatment‐related adverse events (TRAEs) or incidence and sample size. Random‐effect models were employed to study the pooled relative risk (RR) and 95% confidence intervals (CIs). Finally, 36 trials, involving 19,693 participants, fulfilled the inclusion criteria. PD‐1/PD‐L1 inhibitors significantly augmented the likelihood of developing all‐grade (RR, 1.03; 95% CI, 1.01–1.04, p < .01) and grade ≥3 TRAEs (RR, 1.16; 95% CI, 1.10 to 1.23, p < .01). PD‐1/PD‐L1 inhibitors substantially augmented the odds of developing treatment‐related serious adverse events (SAEs) (RR, 1.48; 95% CI, 1.27–1.71, p < .01) and fatal adverse events (FAEs) (RR, 1.42; 95% CI, 1.11–1.82, p < .01). Subgroup analyses indicated that the RR of SAEs and FAEs were generally consistent, regardless of treatment type, tumor type, treatment setting, PD‐1/PD‐L1 inhibitors type and study design. The most common causes of FAEs were respiratory failure/insufficiency (33.3%), cardiac events (16.1%), and hematological disorders (10.1%). We demonstrated that PD‐1/PD‐L1 inhibitors were significantly correlated with higher possibility of developing treatment‐related toxicities, especially SAEs and FAEs, compared with placebo/best supportive care controls.
Potentially functional variants of PARK7 and DDR2 in ferroptosis‐related genes predict survival of non‐small cell lung cancer patients
Authors: Wang Huilin , Liu Hongliang , Tang Xiaozhun , Lu Guojun , Luo Sheng , Du Mulong , Christiani David C. , Wei Qingyi
Published: September 2024

Ferroptosis, a form of regulated cell death, is characterized by iron‐dependent lipid peroxidation. It is recognized increasingly for its pivotal role in both cancer development and the response to cancer treatments. We assessed associations between 370,027 single‐nucleotide polymorphisms (SNPs) within 467 ferroptosis‐related genes and survival of non‐small cell lung cancer (NSCLC) patients. Data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial served as our discovery dataset, while the Harvard Lung Cancer Susceptibility Study used as our validation dataset. For SNPs that remained statistically significantly associated with overall survival (OS) in both datasets, we employed a multivariable stepwise Cox proportional hazards regression model with the PLCO dataset. Ultimately, two independent SNPs, PARK7 rs225120 C>T and DDR2 rs881127 T>C, were identified with adjusted hazard ratios of 1.32 (95% confidence interval = 1.15–1.52, p = .0001) and 1.34 (95% confidence interval = 1.09–1.64, p = .006) for OS, respectively. We aggregated these two SNPs into a genetic score reflecting the number of unfavorable genotypes (NUG) in further multivariable analysis, revealing a noteworthy association between increased NUG and diminished OS (ptrend = .001). Additionally, an expression quantitative trait loci analysis indicated that PARK7 rs225120T genotypes were significantly associated with higher PARK7 mRNA expression levels in both whole blood and normal lung tissue. Conversely, DDR2 rs881127C genotypes were significantly associated with lower DDR2 mRNA expression levels in normal lung tissue. Our findings suggest that genetic variants in the ferroptosis‐related genes PARK7 and DDR2 are associated with NSCLC survival, potentially through their influence on gene expression levels.
Cationic Polystyrene Latex Nanocarriers for Immunostimulatory Long Double‐Stranded RNA Delivery to Ovarian Cancer Cells
Authors: Aldor N. L. , Jadaa N. A. , Miller S. Y. , Alla I. , Richardson S. , Kitaev V. , Poynter S. J.
Published: September 2024

Long double‐stranded (ds)RNA, a potent stimulator of type I interferon and the innate immune response. In the present study, we demonstrated, for the first time, the efficacy of cationic polystyrene latex nanostructures (clNPs) as a dsRNA carrier, improving cellular delivery and robustly potentiating the immunostimulatory capacity of dsRNA in the ovarian cancer cell line SKOV3. The clNPs complexed with an in vitro transcribed dsRNA molecule, were bound by SKOV3 cells, and had increased cellular association compared to uncomplexed clNPs. clNPs complexed with dsRNA induced a more robust innate immune response compared to dsRNA alone. Transcript expression of two interferon‐stimulated genes, were increased 47‐ and 108‐fold over dsRNA and induced a significant antiviral state against vesicular‐stomatitis virus, resulting in a 3.3‐fold improvement on the efficacy of dsRNA. These data highlight the potential of polystyrene latex nanostructures as dsRNA carriers for anticancer immunotherapies, improving the uptake and efficacy of the nucleic acid.
Sub‐acute bisphenol A exposure induces proteomic alterations and impairs male reproductive health in mice
Authors: Yadav Shiv K. , Kumar Arvind , Yadav Bal G. , Bijalwan Vandana , Yadav Suresh , Patil Gajanan P. , Sarkar Kamalesh , Palkhade Rajendra , Das Santasabuj , Singh Dhirendra P.
Published: September 2024

Bisphenol A (BPA) is one of the most prevalent endocrine disrupting chemicals (EDCs) and there is widespread concern about the adverse effects of EDCs on human health. However, the exact mechanism of these toxicities has still not been fully deciphered. Additionally, studies have reported the toxicological effects at far low doses to the generally considered no‐observed‐adverse‐effect level (NOAEL) dose. The present study investigates the effects of a sub‐acute (28 days) exposure to BPA (10, 50 and 100 mg/kg/day) in adult male mice on various hormones levels, sperm motility, sperm count, functional integrity of sperm plasma membrane, testicular histological changes, oxidative stress markers and DNA damage. The key proteome signatures were quantified by LC‐MS/MS analysis using Orbitrap Fusion Lumos Tribrid Mass Spectrometer equipped with nano‐LC Easy‐nLC 1200. Data suggest that the BPA exposure in all doses (below/above NOAEL dose) have greatly impacted the hormone levels, sperm parameters (sperm count, motility and membrane integrity) and testicular histology. Mass spectrometry‐based proteomics data suggested for 1352 differentially expressed proteins (DEPs; 368 upregulated, 984 downregulated) affecting biological process, cellular component, and molecular functions. Specifically searched male reproductive function related proteins suggested a complex network where 46 potential proteins regulating spermatogenesis, sperm structure, activity and membrane integrity while tackling oxidative stress responses were downregulated. These potential biomarkers could shed some more light on our current understanding of the reproductive toxicological effects of BPA and may lead to exploration of novel interventions strategies against these targets for male infertility.
The ameliorative effect of carvacrol on sodium arsenite‐induced hepatotoxicity in rats: Possible role of Nrf2/HO‐1, RAGE/NLRP3, Bax/Bcl‐2/Caspase‐3, and Beclin‐1 pathways
Authors: Gencer Selman , Gür Cihan , İleritürk Mustafa , Küçükler Sefa , Akaras Nurhan , Şimşek Hasan , Kandemir Fatih M.
Published: September 2024

Arsenic is a toxic environmental pollutant heavy metal, and one of its critical target tissues in the body is the liver. Carvacrol is a natural phytocompound that stands out with its antioxidant, anti‐inflammatory, and antiapoptotic properties. The current study aims to investigate the protective feature of carvacrol against sodium arsenite‐induced liver toxicity. Thirty‐five Sprague‐Dawley male rats were divided into five groups: Control, Sodium arsenite (SA), CRV, SA + CRV25, and SA + CRV50. Sodium arsenite was administered via oral gavage at a dose of 10 mg/kg for 14 days, and 30 min later, CRV 25 or 50 mg/kg was administered via oral gavage. Oxidative stress, inflammation, apoptosis, autophagy damage pathways parameters, and liver tissue integrity were analyzed using biochemical, molecular, western blot, histological, and immunohistological methods. Carvacrol decreased sodium arsenite‐induced oxidative stress by suppressing malondialdehyde levels and increasing superoxide dismutase, catalase, glutathione peroxidase activities, and glutathione levels. Carvacrol reduced inflammation damage by reducing sodium arsenite‐induced increased levels of NF‐κB and the cytokines (TNF‐α, IL‐1β, IL‐6, RAGE, and NLRP3) it stimulates. Carvacrol also reduced sodium arsenite‐induced autophagic (Beclin‐1, LC3A, and LC3B) and apoptotic (P53, Apaf‐1, Casp‐3, Casp‐6, Casp‐9, and Bax) parameters. Carvacrol preserved sodium arsenite‐induced impaired liver tissue structure. Carvacrol alleviated toxic damage by reducing sodium arsenite‐induced increases in oxidative stress, inflammation, apoptosis, and autophagic damage parameters in rat liver tissues. Carvacrol was also beneficial in preserving liver tissue integrity.
USP1‐mediated deubiquitination of KDM1A promotes the malignant progression of triple‐negative breast cancer
Authors: Su Yang , Du Yan , He Wenguang
Published: September 2024

Previous research has indicated the highly expressed lysine‐specific histone demethylase 1A (KDM1A) in several human malignancies, including triple‐negative breast cancer (TNBC). However, its detailed mechanisms in TNBC development remain poorly understood. The mRNA levels of KDM1A and Yin Yang 1 (YY1) were determined by RT‐qPCR analysis. Western blot was performed to measure KDM1A and ubiquitin‐specific protease 1 (USP1) protein expression. Cell proliferation, apoptosis, invasion, migration and stemness were evaluated by MTT assay, EdU assay, flow cytometry, transwell invasion assay, wound‐healing assay and sphere‐formation assay, respectively. ChIP and dual‐luciferase reporter assays were conducted to determine the relationship between YY1 and KDM1A. Xenograft tumor experiment and IHC were carried out to investigate the roles of USP1 and KDM1A in TNBC development in vivo. The highly expressed KDM1A was demonstrated in TNBC tissues and cells, and KDM1A knockdown significantly promoted cell apoptosis, and hampered cell proliferation, invasion, migration, and stemness in TNBC cells. USP1 could increase the stability of KDM1A via deubiquitination, and USP1 depletion restrained the progression of TNBC cells through decreasing KDM1A expression. Moreover, YY1 transcriptionally activated KDM1A expression by directly binding to its promoter in TNBC cells. Additionally, USP1 inhibition reduced KDM1A expression to suppress tumor growth in TNBC mice in vivo. In conclusion, YY1 upregulation increased KDM1A expression via transcriptional activation. USP1 stabilized KDM1A through deubiquitination to promote TNBC progression.
MEOX1 triggers myofibroblast apoptosis resistance, contributing to pulmonary fibrosis in mice
Authors: Jin Ling , Bao Bo , Huang Xiao‐Ting , Tao Jia‐Hao , Duan Jia‐Xi , Zhong Wen‐Jin , Zhang Chen‐Yu , Liu Yu‐Biao , Chen Hui , Yang Nan‐Shi‐Yu , Guan Cha‐Xiang , Zhou Yong
Published: September 2024

The apoptosis resistance of myofibroblasts is a hallmark in the irreversible progression of pulmonary fibrosis (PF). While the underlying molecular mechanism remains elusive. In this study, we unveiled a previously unrecognized mechanism underlying myofibroblast apoptosis resistance during PF. Our investigation revealed heightened expression of mesenchyme homeobox 1 (MEOX1) in the lungs of idiopathic pulmonary fibrosis (IPF) patients and bleomycin‐induced PF mice. Silencing MEOX1 significantly attenuated PF progression in mice. In vitro, we found a notable increase in MEOX1 expression in transforming growth factor‐β1 (TGF‐β1)‐induced myofibroblasts. Silencing MEOX1 enhanced apoptosis of myofibroblasts. Mechanistically, we identified G‐protein signaling pathway regulatory factor 4 (RGS4) as a critical downstream target of MEOX1, as predicted by bioinformatics analysis. MEOX1 enhanced apoptosis resistance by upregulating RGS4 expression in myofibroblasts. In conclusion, our study highlights MEOX1 as a promising therapeutic target for protecting against PF by modulating myofibroblast apoptosis resistance.
Decreased histone H3K9 dimethylation in synergy with DNA demethylation of Spi‐1 binding site contributes to ADAMTS‐5 expression in articular cartilage of osteoarthritis mice
Authors: Yan Shuaichen , Lu Tongxin , Yang Huapu , Ma Liang , Zhang Yuankai , Li Deqiang
Published: September 2024

Osteoarthritis (OA) is defined by articular cartilage degeneration, synovial membrane inflammation, and abnormal bone remodeling. Recent study has discovered that OA development is linked to an aberrant epigenetic modification of OA‐related genes. Our previous research showed that DNA demethylation in ADAMTS‐5 promoter region had a substantial impact on ADAMTS‐5 expression in the mouse OA model. This process facilitated the binding of Spi‐1 to ADAMTS‐5 promoter. While alterations in histone methylation have been documented during embryonic development and cancer development, there is a paucity of data on the change in OA pathogenesis. Even no data have been reported on the role of histone modifications in ADAMTS‐5 activation in OA. Following our previous study on the role of DNA methylation, we aimed to examine the contribution of histone H3K9 dimethylation in ADAMTS‐5 activation in OA. Additionally, we aimed to elucidate the molecular mechanisms underlying the cooperative interaction between DNA methylation and histone H3K9 dimethylation. The potential for anti‐OA intervention therapy which is based on modulating histone H3K9 dimethylation is also explored. We demonstrated that a reduction in histone H3K9 dimethylation, along with DNA demethylation of the Spi‐1 binding site, had a role in ADAMTS‐5 activation in the articular cartilage of OA mice. Significantly, the conditional deletion of histone demethylase to be identified as lysine‐specific demethylase 1 (LSD1) in articular cartilage could alleviate the degenerative features of OA mice. Our study demonstrates the direct impact of histone H3K9 dimethylation on gene expression, which in turn contributes to OA development. This research enhances our understanding of the underlying causes of OA.
Younger age, hyperextended knee, concomitant meniscectomy and large prerevision anterior tibial translation are associated with graft failure after the revision anterior cruciate ligament reconstruction
Authors: Tokura Takeo , Matsushita Takehiko , Nishida Kyohei , Nagai Kanto , Kanzaki Noriyuki , Hoshino Yuichi , Matsumoto Tomoyuki , Kuroda Ryosuke
Published: September 2024

Purpose

Graft failure following revision anterior cruciate ligament (ACL) reconstruction is higher than after primary ACL reconstruction. However, data regarding revision surgery is scarce. We aimed to evaluate the associated factors for failure after revision ACL reconstruction.

Methods

Fifty‐four patients (mean age: 24.7 ± 10.0 years) who underwent revision ACL reconstruction at our hospital with ≥1 year follow‐up were retrospectively examined. Patients were divided into Group F (graft failure) and Group N (no graft failure) groups. Univariate analysis was conducted to identify factors associated with graft failure. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal thresholds for differentiating between the two groups.

Results

Graft failure was observed in 7 of 54 patients (13.0%). In the univariate analysis, significant differences were observed for age at the initial surgery (Group F: 15.6 ± 1.5, Group N: 20.9 ± 8.1), age at the revision surgery (Group F: 18.0 ± 2.8, Group N: 25.7 ± 10.3), presence of hyperextended knee (Group F: 85.7%, Group N: 14.9%), concomitant meniscectomy (Group F: 42.9%, Group N: 14.9%), prerevision space for the ACL (sACL) (Group F: 7.2 ± 3.4 mm, Group N: 13.4 ± 4.7 mm) and preoperative anterior tibial translation (ATT) (Group F: 5.0 ± 1.4 mm, Group N: 2.7 ± 3.1 m). ROC analysis of preoperative sACL and preoperative ATT on one‐leg standing plain radiograph showed that cutoff values of 6.9 and 4.2 mm were the optimal thresholds, respectively.

Conclusion

Younger patients with a hyperextended knee, concomitant meniscectomy, small sACL and large ATT before revision ACL reconstruction are predisposed to graft failure.

Level of Evidence

Level IV.
Is corruption an input material for environmental pollution?
Authors: Van Hung Hoang , Doanh Nguyen Khanh
Published: September 2024

This study examines the impact of corruption on environmental quality, covering aspects such as climate change, environmental health, air quality, sanitation and drinking water, heavy metals, and waste management across 163 countries from 2005 to 2020. We utilize a spatial autoregressive (SAR) model for panel data to analyse the spatial dependencies among these environmental quality indicators. Our findings highlight several key insights. First, there are spatial spillover effects in regional environmental quality, particularly concerning climate change, air quality, and waste management. Second, a country's environmental quality is influenced not only by its own corruption control measures but also by those of its neighbouring countries. Finally, our analysis identifies variations across different income groups: while control of corruption significantly and positively impacts environmental quality in high‐income and medium‐income countries, its effect is positive but statistically insignificant in low‐income countries. These results emphasize the need for tailored environmental policies for each income group and environmental aspect.
Microsecond Molecular Dynamics Simulation to Gain Insight Into the Binding of MRTX1133 and Trametinib With KRASG12D Mutant Protein for Drug Repurposing
Authors: Ancy Iruthayaraj , Penislusshiyan Sakayanathan , Ameen Fuad , Chitra Loganathan
Published: September 2024

The Kirsten Rat Sarcoma (KRAS) G12D mutant protein is a primary driver of pancreatic ductal adenocarcinoma, necessitating the identification of targeted drug molecules. Repurposing of drugs quickly finds new uses, speeding treatment development. This study employs microsecond molecular dynamics simulations to unveil the binding mechanisms of the FDA‐approved MEK inhibitor trametinib with KRASG12D, providing insights for potential drug repurposing. The binding of trametinib was compared with clinical trial drug MRTX1133, which demonstrates exceptional activity against KRASG12D, for better understanding of interaction mechanism of trametinib with KRASG12D. The resulting stable MRTX1133‐KRASG12D complex reduces root mean square deviation (RMSD) values, in Switch I and II domains, highlighting its potential for inhibiting KRASG12D. MRTX1133's robust interaction with Tyr64 and disruption of Tyr96‐Tyr71‐Arg68 network showcase its ability to mitigate the effects of the G12D mutation. In contrast, trametinib employs a distinctive binding mechanism involving P‐loop, Switch I and II residues. Extended simulations to 1 μs reveal sustained network interactions with Tyr32, Thr58, and GDP, suggesting a role of trametinib in maintaining KRASG12D in an inactive state and impede the further cell signaling. The decomposition binding free energy values illustrate amino acids' contributions to binding energy, elucidating ligand–protein interactions and molecular stability. The machine learning approach reveals that van der Waals interactions among the residues play vital role in complex stability and the potential amino acids involved in drug–receptor interactions of each complex. These details provide a molecular‐level understanding of drug binding mechanisms, offering essential knowledge for further drug repurposing and potential drug discovery.
Education and Training in Peritoneal Surface Oncology
Authors: González‐Moreno Santiago , Deraco Marcello , Kusamura Shigeki , Bijelic Lana , Lambert Laura A. , Dromain Clarisse , Bibeau Frédéric , Liauw Winston , Reis Artur , Galan Ana , Sugarbaker Paul H.
Published: September 2024

Peritoneal surface oncology (PSO) is a novel field dealing with the knowledge of peritoneal neoplasms, primary or secondary, and their clinical management. As a specific treatment with curative intent for peritoneal neoplasms developed over the years, there is a growing need to comprehensively educate and train surgical oncologists worldwide in this discipline, a recognized unmet need. The European School of Peritoneal Surface Oncology (ESPSO) emerged in 2014 to provide an answer to this need.
Quality of Life Post Cervical Cancer Treatment: A Comparison Between Radical Surgery Approach and Radiotherapy and Chemotherapy
Authors: Tokarski Alyne O. , Bernardelli Rafaella S. , Bruscato Julia R. , Lucena Claudio R. , Linhares Jose C. , Tsunoda Audrey T.
Published: September 2024

Introduction

The assessment of quality of life (QoL) in women with cervical cancer is crucial due to the profound changes they undergo during and after treatment. Often, the significance of sexual factors is underestimated, likely due to societal taboos surrounding such discussions.

Objective

This study aimed to determine the long‐term QoL outcomes, particularly focusing on sexuality, among three therapeutic approaches for cervical cancer: chemotherapy, radiotherapy, and brachytherapy; isolated hysterectomy; and hysterectomy combined with radiotherapy.

Methods

Conducted from November 2022 to July 2023, this cross‐sectional study involved 131 cervical cancer patients. Their QoL was assessed using the MDASI, FACIT‐Cx, and risk factor questionnaires. Results were compared across the three treatment groups, revealing notable differences.

Results

Patients undergoing chemo/radio/brachytherapy showed significantly lower QoL scores compared to those undergoing isolated hysterectomy. This was evident in reduced scores across FACIT‐Cx subscales for physical well‐being, specific concerns, and FACIT‐total (p < 0.05). The MDASI results similarly indicated greater symptoms and interference in daily activities for the chemo/radio/brachytherapy group.

Conclusion

In conclusion, isolated hysterectomy, demonstrated superior QoL outcomes compared to chemo/radio/brachytherapy. Furthermore, the study underscored the importance of addressing sexual concerns in QoL assessments of cervical cancer survivors, emphasizing the need for comprehensive care to enhance overall well‐being posttreatment.
Examining the impact of brief couples‐based posttraumatic stress disorder treatments on anger and psychological aggression in veterans and their partners
Authors: Wells Stephanie Y. , Knopp Kayla , Wachsman Tamara R. , Dillon Kirsten H. , Walker Hannah E. , Sippel Lauren , Morland Leslie , Glassman Lisa H.
Published: September 2024

Anger can adversely impact functioning in veterans. Psychological aggression, which is related to but distinct from anger, is particularly detrimental to veterans’ mental health. Research examining anger and psychological aggression following individual therapy for posttraumatic stress disorder (PTSD) has demonstrated small effect sizes. Treatments that directly target conflict management and interpersonal functioning, both regarding content and delivery to veterans and their loved ones (e.g., couples‐based PTSD treatments), may be more effective in alleviating anger symptoms. This study examined whether larger reductions in anger and psychological aggression would be observed in a couples‐based intervention compared to an active comparator at posttreatment and follow‐up. Data were derived from a randomized trial comparing brief cognitive–behavioral conjoint therapy for PTSD (bCBCT) and PTSD family education (PFE). Participants were 137 veterans and their intimate partners (bCBCT: n = 92, PFE: n = 45). We observed within‐condition significant reductions in angry temperament, d = ‐0.47, p < .001, and angry reaction, d = −0.26, p = .004, among veterans in bCBCT but not PFE, |d|s = 0.13–0.17, ps = .166–.268. Veterans and partners in both conditions reported reductions in psychological aggression, |d|s = 1.09–1.46, ps < .001. There were no significant differences between the treatment conditions on any outcome, ps = .103–.443, and there were no significant changes in anger between posttreatment and follow‐up, |d|s = 0.07–0.24, ps = .052–.582. Couples‐based interventions for PTSD, including bCBCT and PFE, can be effective in improving aspects of anger among veterans and their intimate partners.
Microbial Community and Functions Depending on Tillage and Straw Returning Management: Consequences for Soil Health and Ecosystem Services
Authors: Liu Qing , Dai Hongcui , Wang Liang , Qian Xin , Gao Yingbo , Zhang Hui , Liu Kaichang , Li Zongxin , Zamanian Kazem
Published: September 2024

Tillage and straw returning are promising practices to improve soil quality, especially because of the unclear controlling effects on microbial communities and functions. A 5‐year field experiment in a winter wheat‐summer maize cropping system was implemented in the North China Plain to address this research gap. Management practices were deep tillage, rotary tillage, and no‐tillage, each with either wheat only or both wheat and maize straw returning. Shotgun metagenomic sequencing was performed to investigate the microbial community, diversity, co‐occurrence network, and function in the topsoil (0–20 cm). The associations between soil physiochemical properties and microbial community characteristics were also evaluated. Rotary tillage with only wheat straw returning (RTS) significantly increased Shannon's diversity index by 0.24%–1.71% compared to other treatments. No‐tillage with only wheat straw returning (NTS) showed the most stable microbial network with the highest betweenness centrality (199.09), average path distance (2.31), and modularity (0.50). NTS had the highest relative abundance of microbial carbon (C), nitrogen (N) metabolisms, and C fixation pathways. Among deep tillage practices, both wheat and maize straw returning (DTD) were more beneficial to the stability of microbial networks than only wheat straw returning (DTS), yet without improvement in microbial diversity and function. In conclusion, microbial community and function are practical predictors of variations in soil nutrient availability, and pH value in response to different tillage and residue management practices. In particular, our study provides a basis for the development of a sustainable crop residue management system.
High‐Shear Enhancement of Biginelli Reactions in Macromolecular Viscous Media
Authors: Bui Aaron Hung , Rowlands Naomi Beth , Fernando Pulle Anne Dilpashani , Gibbs Medina Sam Andrés , Rohrsheim Tullia Jade , Tuten Bryan Tyler
Published: September 2024

Chemical reactions and transformations in non‐traditional vessels have gained significant interest in recent years. Flow chemistry, with its advantages in mixing, mass transfer, scalability, and automation, is a driving force behind this paradigm shift. In particular, the Vortex Fluidic Device (VFD) has emerged as a versatile tool across various applications, from organic synthesis to materials science. In this study, the role of the VFD in performing the Biginelli reaction, a multicomponent reaction widely used in pharmaceutical and polymer science, for a post‐polymerization modification is explored. By conducting the Biginelli reaction in the VFD, rapid product formation with low catalyst loading and without the need for high temperatures is achieved. However, the critical need to understand and know solution viscosity, especially within the context of modifying macromolecules is highlighted.
ω‐3 PUFAs Ameliorated the Maternal High‐Fructose Diet‐Induced Early‐Onset Retinopathy in Offspring via Inhibiting NLRP3‐Associated Neuroinflammation
Authors: Huang Hsiu‐Mei , Chang Ying‐Chao , Lee Jong‐Jer , Huang Yao‐Sheng , Wu Kay L. H.
Published: September 2024

Scope

Maternal high fructose diet (HFD) during pregnancy and lactation can initiate retinal dysfunction. However, the underlying mechanism remains largely unknown.

Methods and results

By using the rodent model of maternal HFD in this study, the results from electroretinography (ERG) indicate that b‐wave amplitude, an index of inner retinal function, is significantly reduced as early as 3 months old and the deteriorated effect can be detected at 15 months old. Further, the protein expressions of CD11b (a marker of active microglia), p40phox subunit of NADPH oxidase, GFAP (a marker of active astrocytes), and NLPR3 examined by western blot and immunofluorescence are significantly increased in the retina of the male HFD offspring at 3 months old. Treatment with omega‐3 polyunsaturated fatty acids (ω‐3 PUFAs) for 2 weeks (from 2.5 to 3 months old) effectively reverses the aforementioned changes.

Conclusion

Together, these results indicate that the early onset and extensive retinal dysfunction may be a result of glial activation which is induced by maternal HFD to initiate an inflammatory microenvironment leading to a long‐term progression of retinopathy. Short‐term administration of ω‐3 PUFA at a young age may be a feasible strategy to intervene in the maternal HFD‐programmed retinal impairment in male offspring.
Monomethyl Branched‐Chain Fatty Acids Suppress M1 Macrophage Polarization via FABP4/PPAR‐γ Signaling Pathway
Authors: He Yuan , Zhang Yu , Zhu Shuang , Liu Yuan‐fa , Liu Sha , Xu Yong‐jiang
Published: September 2024

Scope

Monomethyl‐branched chain fatty acids (mmBCFAs) are found in a variety of food sources and are of great interest due to their potent antiinflammatory properties. However, most of the current researches have concentrated on the relationship between mmBCFAs and intestinal inflammation, and there is a large gap in the biological mechanisms involved behind their antiinflammatory effects.

Methods and results

The present study examines the role of mmBCFAs in modulating macrophage polarization. The results demonstrate that iso‐C16:0 significantly inhibits macrophages M1 proinflammatory polarization through regulating FABP4/PPAR‐γ pathway. Proteomics and molecular biology experiments verify that metabolic reprogramming is involved in the inhibition of M1 macrophage, referring to the upregulation of fatty acid oxidation, TCA cycle, and oxidative phosphorylation, as well as downregulation of glycolytic flux.

Conclusion

In summary, this study offers a novel perspective on the antiinflammatory effects mediated by mmBCFAs.
Coronary atherosclerotic plaque characterization with silicon‐based photon‐counting computed tomography (CT): A simulation‐based feasibility study
Authors: Li Mengzhou , Wu Mingye , Pack Jed , Wu Pengwei , Yan Pingkun , De Man Bruno , Wang Adam , Nieman Koen , Wang Ge
Published: September 2024

Background

Recent photon‐counting computed tomography (PCCT) development brings great opportunities for plaque characterization with much‐improved spatial resolution and spectral imaging capability. While existing coronary plaque PCCT imaging results are based on CZT‐ or CdTe‐materials detectors, deep‐silicon photon‐counting detectors offer unique performance characteristics and promise distinct imaging capabilities.

Purpose

This study aims to numerically investigate the feasibility of characterizing plaques with a deep‐silicon PCCT scanner and to demonstrate its potential performance advantages over traditional CT scanners using energy‐integrating detectors (EID).

Methods

We conducted a systematic simulation study of a deep‐silicon PCCT scanner using a newly developed digital plaque phantom with clinically relevant geometrical and chemical properties. Through qualitative and quantitative evaluations, this study investigates the effects of spatial resolution, noise, and motion artifacts on plaque imaging.

Results

Noise‐free simulations indicated that PCCT imaging could delineate the boundary of necrotic cores with a much finer resolution than EID‐CT imaging, achieving a structural similarity index metric (SSIM) score of 0.970 and reducing the root mean squared error (RMSE) by two‐thirds. Measuring necrotic core area errors were reduced from 91.5% to 24%, and fibrous cap thickness errors were reduced from 349.8% to 33.3%. In the presence of noise, the optimal reconstruction was achieved using 0.25 mm voxels and a soft reconstruction kernel, yielding the highest contrast‐to‐noise ratio (CNR) of 3.48 for necrotic core detection and the best image quality metrics among all choices. However, the ultrahigh resolution of PCCT increased sensitivity to motion artifacts, which could be mitigated by keeping residual motion amplitude below 0.4 mm.

Conclusions

The findings suggest that deep‐silicon PCCT scanner can offer sufficient spatial resolution and tissue contrast for effective plaque characterization, potentially improving diagnostic accuracy in cardiovascular imaging, provided image noise and motion blur can be mitigated using advanced algorithms. This simulation study involves several simplifications, which may result in some idealized outcomes that do not directly translate to clinical practice. Further validation studies with physical scans are necessary and will be considered for future work.
Differentiating leukemia subtypes based on metabolic signatures using hyperpolarized 13C NMR
Authors: Christensen Nichlas Vous , Laustsen Christoffer , Bertelsen Lotte Bonde
Published: September 2024

Leukemia is a group of blood cancers that are classified in four major classes. Within these four classes, many different subtypes exists with similar origin, genetic mutations, and level of maturity, which can make them difficult to distinguish. Despite their similarities, they might respond differently to treatment, and therefore distinguishing between them is of crucial importance. A deranged metabolic phenotype (Warburg effect) is often seen in cancer cells, leukemia cells included, and is increasingly a target for improved diagnosis and treatment. In this study, hyperpolarized 13C NMR spectroscopy was used to characterize the metabolic signatures of the six leukemia cell lines ML‐1, CCRF‐CEM, THP‐1, MOLT‐4, HL‐60, and K562. This was done using [1‐13C]pyruvate and [1‐13C]alanine as bioprobes for downstream metabolite quantification and kinetic analysis on cultured cells with and without 2‐deoxy‐D‐glucose treatment. The metabolic signatures of similar leukemia subtypes could be readily distinguished. This includes ML‐1 and THP‐1, which are of the similar M4 and M5 AML subtypes, CCRF‐CEM and MOLT‐4, which are of the similar T‐ALL lineage at different maturation states, and HL‐60 and K562, which are of the closely related M1 and M2 AML subtypes. The data presented here demonstrate the potential of hyperpolarized 13C NMR spectroscopy as a method to differentiate between leukemia subtypes of similar origin. Combining this method with bioreactor setups could potentially allow for better leukemia disease management as metabolic signatures could be acquired from a single biopsy through repeated experimentation and intervention.