bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced recovery in type A aortic dissection evaluating the efficacy and feasibility of early myocardial reperfusion
Authors: Niu Tianyu , Liu Zhishuo , Liu Yu , Yang Zhonglu , Ge Yuguang , Wang Lu , Xia Lin , Jiang Hui
Published: January 2025

Background

This study investigates the feasibility and early outcomes of early myocardial reperfusion in patients with type A aortic dissection (TAAD), evaluating its effectiveness and potential benefits compared to traditional cardioplegic arrest techniques.

Methods

A retrospective analysis was conducted on 168 patients diagnosed with TAAD who underwent surgery at the General Hospital of the Northern Theater Command in China from January 2021 to July 2024. Patients were divided into two groups: early myocardial reperfusion (EMR group, n = 66) and cardioplegic arrest (CA group, n = 102). Perioperative outcomes were compared between the groups.

Results

Early myocardial reperfusion significantly reduced ventilation time 23.08 (18.21, 66.74) hours vs. 48.58 (19.18, 122.97) hours, P < 0.05], ICU stay time [58.80 (21.20, 126.68) hours vs. 84.86 (41.12, 168.81) hours, P < 0.05], and hospitalization time [13.00 (10.00, 16.00) days vs. 15.00 (11.75, 19.00) days, P < 0.05] compared to the CA group. There was no significant difference in hospital costs, first-hour chest tube drainage, left ventricular ejection fraction, or postoperative adverse events between the groups, except for the rate of CRRT treatment, where the EMR group had significantly fewer patients requiring postoperative CRRT (10.6% vs. 23.5%, P < 0.05).

Conclusion

This study demonstrates that early myocardial reperfusion is a feasible and effective technique for TAAD, offering considerable advantages in reducing ventilation time, ICU stay, hospitalization duration and postoperative renal insufficiency.
Teacher professional learning communities and children’s school readiness in China: the moderating role of supportive conditions and cooperative atmosphere
Authors: Ren Jie , Mo Yunjuan , Zhang Yulong , Hou Yuna
Published: January 2025

Introduction

This study examined whether teacher professional learning communities (PLCs) established through a collaborative effort between kindergarten and primary school teachers can effectively promote Chinese children’s school readiness and explore the policy conditions that stimulate such a facilitative effect.

Methods

A total of 839 children and 67 teachers in kindergartens from Chongqing, China, participated in this study. Firstly, we used descriptive statistical analysis to determine the overall situation of teacher PLCs. Subsequently, a series of mean difference tests and multiple linear regression analysis were used to test the relationship between teacher PLCs and children’s school readniess.

Results

The results indicated that the three dimensions of teacher PLCs, including shared vision, collaborative practice, and resource sharing, significantly and positively predicted children’s school readiness. Chinese teachers scored highest in the dimension of shared vision, followed by collaborative practice, and lowest in resource sharing. The collaborative atmosphere of teacher PLCs enhanced their effects on children’s school readiness, while the supportive conditions of teacher PLCs were ineffective.

Discussion

The empirical findings from this study broaden the scope of existing research on teacher PLCs and provide information from a Chinese context about improving children’s early development to benefit international society.
Impact of the initiation of isCGM soon after type 1 diabetes mellitus diagnosis in adults on glycemic indices and fear of hypoglycemia: a randomized controlled trial
Authors: Hohendorff Jerzy , Grzelka-Wozniak Agata , Wrobel Marta , Kania Michal , Lapinska Lidia , Rokicka Dominika , Stoltny Dorota , Kowalska Irina , Strojek Krzysztof , Zozulinska-Ziolkiewicz Dorota , Malecki Maciej T.
Published: January 2025

Background

Continuous glucose monitoring (CGM) improves glycemic control and quality of life. Data on glycemic indices and fear of hypoglycemia (FoH) in newly diagnosed T1DM patients are limited.

Aim

To assess the impact of initiating intermittently scanned CGM (isCGM) within 1–6 months of diagnosis on glycemic control and FoH in adults with T1DM.

Subjects and methods

After wearing a blinded sensor for 14 days, participants were randomized (1:1) to either isCGM (intervention) or self-monitoring blood glucose (SMBG) with glucometers and blinded CGM (control). Primary outcomes were changes in time below 70 mg/dl (TB70) and FoH, assessed in the Hypoglycemia Fear Survey (HFS). Main secondary outcomes included changes in mean glucose and time in range (TIR) from baseline to 4 weeks after randomization.

Results

The full analysis set included 23 patients (12 from the intervention group and 11 from the control group), aged 25.6 ± 5.1 years (14 men, 9 women). All participants were on multiple daily insulin injections. TB70 changed from 2.42% to 2.25% in the intervention, and from 2.81% to 1.82% in the control group, and the between-therapy difference of 0.83% was insignificant. No difference between intervention and control groups in change in HFS-worry and HFS-behavior subscales between baseline and after 4 weeks was found (−1.6 ± 3.2 and 1.0 ± 2.2, respectively). The mean glucose levels changed from 7.03 mmol/l to 6.73 mmol/l and from 7.07 mmol/l to 7.43 mmol/l, in the intervention and control groups, respectively, which resulted in a between-therapy significant glucose difference of −0.66 mmol/l. The mean TIR changed from 88.0% to 90.0% in the intervention group and from 85.2 to 84.1% in the control group—the between-therapy difference was insignificant (3,1%). The study ended early due to CGM reimbursement policy changes, after which most patients eligible for the study could have isCGM reimbursed.

Conclusions

In newly diagnosed T1DM adults, TIR is high and hypoglycemia risk is low. The study group was small; however, the data suggest that the use of isCGM soon after T1DM diagnosis could result in mean glucose decrease, but not in change in TB70 and FoH.
Unexplored avenues: a narrative review of cognition and mood in postmenopausal African women with female genital circumcision/mutilation/cutting
Authors: Kumar Rohina , Calvo Noelia , Einstein Gillian
Published: January 2025

Recent ageing research has projected the lifespan and proportion of postmenopausal women living in low- and middle-income countries to substantially increase over the years, especially on the African continent. An important subgroup within the African postmenopausal population is those with female genital circumcision/mutilation/cutting (FGC). Practised across 31 African nations, FGC holds cultural significance as it is deemed essential to marriage and successful womanhood. Perhaps because of this, most FGC studies have primarily focused on women's reproductive functioning and their mood experiences. These studies also usually exclude postmenopausal women from their cohorts. Consequently, cognition and age-related cognitive decline and preservation remain understudied. Therefore, we investigated what is known about mood and cognition in local and immigrant postmenopausal African women with FGC. To do this, we carried out a narrative review searching PubMed, PsycInfo, and Google Scholar databases. Boolean combinations of keywords related to FGC, cognition, ageing, and mood were used, with a focus on cognition and ageing-related terms. Only studies published in English, those that recruited African women with FGC aged 50 years and older, and those that investigated cognitive and/or mood-related experiences were included. Ten studies were found; these included quantitative, qualitative, and case reports. The age range of cohorts across included studies was 13–90 years; women who were likely postmenopausal formed a minority within the cohorts (4.5%–25%). There were no studies assessing memory or cognition beyond those looking at FGC-related memories, which were vivid, especially if women had type III FGC (Pharaonic) or were older at the time of FGC. Although most of these women reported experiencing negative emotions concerning FGC, quantitative reports showed that only a minority of women experienced post-traumatic stress disorder, anxiety, or depression. Thus, there remains an urgent need to bring this understudied group into ageing and dementia research. Future research should adopt mixed-methods with culturally sensitive methodologies to investigate the lived experience of ageing as well as cognitive changes. A holistic understanding of ageing women from the Horn of Africa's experiences and needs will support an improvement in the quality of care delivered to this cohort in both local and immigrant contexts.
HMGB1 lactylation drives neutrophil extracellular trap formation in lactate-induced acute kidney injury
Authors: Zhu Li , Zheng Qiang , Liu Xiaodong , Ding Hao , Ma Mengqing , Bao Jiaxin , Cai Yawen , Cao Changchun
Published: January 2025

Rationale

Acute kidney injury (AKI) is a clinical syndrome associated with a multitude of conditions. Although renal replacement therapy (RRT) remains the cornerstone of treatment for advanced AKI, its implementation can potentially pose risks and may not be readily accessible across all healthcare settings and regions. Elevated lactate levels are implicated in sepsis-induced AKI; however, it remains unclear whether increased lactate directly induces AKI or elucidates the underlying mechanisms.

Methods

For human, the measurement of lactate in arterial blood gas is performed using the direct determination of L-lactate through an electrode oxidation method by a blood gas analyzer. For mice, enzyme-linked immunosorbent assay (ELISA) kits were employed to quantify the concentrations of lactate and AKI biomarkers in blood and cell supernatant. The mouse model of AKI was performed with a single intraperitoneal (i.p.) administration of lactate (30 mg/kg) and low-dose LPS (2 mg/kg) for 24 h. Proteomic analysis was conducted to identify lactylated proteins in kidney tissues. Techniques such as, immunoprecipitation, western blotting and immunofluorescence were used to evaluate the levels of HMGB1 lactylation, neutrophil extracellular traps (NETs)and to assess related molecular signaling pathways.

Main results

Our findings indicate that lactate serves as an independent predictor of AKI in patients with acute decompensated heart failure (ADHF). We observed that co-administration of lactate with low-dose lipopolysaccharide (LPS) resulted in lactate overproduction, which subsequently elevated serum levels of creatinine (Cre) and blood urea nitrogen (BUN). Furthermore, the combined application of lactate and low-dose LPS was shown to provoke HMGB1 lactylation within renal tissues. Notably, pretreatment with HMGB1 small interfering RNA (siRNA) effectively diminished lactate-mediated HMGB1 lactylation and alleviated the severity of AKI. Additionally, lactate accumulation was found to enhance the expression levels of NETs in the bloodstream, with circulating NETs levels positively correlating with HMGB1 lactylation. Importantly, pre-administration of HMGB1 inhibitors (glycyrrhizin) or lactate dehydrogenase A (LDH-A) inhibitors (oxamate) reversed the upregulation of NETs induced by lactate and low-dose LPS in both the blood and polymorphonuclear neutrophils (PMNs) cell supernatant, thereby ameliorating AKI associated with lactate accumulation.

Conclusions

These findings illuminate the role of lactate-mediated HMGB1 lactylation in inducing AKI in mice through the activation of the HMGB1-NETs signaling pathway.
Eosinophil is a predictor of severe immune-related adverse events induced by ipilimumab plus nivolumab therapy in patients with renal cell carcinoma: a retrospective multicenter cohort study
Authors: Tasaki Yoshihiko , Hamamoto Shuzo , Yamashita Shimpei , Furukawa Junya , Fujita Kazutoshi , Tomida Ryotaro , Miyake Makito , Ito Noriyuki , Iwamoto Hideto , Mimura Yoshihisa , Sugiyama Yosuke , Unno Rei , Okada Atsushi , Yasui Takahiro , Furukawa-Hibi Yoko
Published: January 2025

Introduction

Immune-related adverse events (irAEs) induced by immune checkpoint inhibitors are difficult to predict and can lead to severe events. Although it is important to develop strategies for the early detection of severe irAEs, there is a lack of evidence on irAEs associated with ipilimumab plus nivolumab therapy for metastatic renal cell carcinoma (RCC). Therefore, this study aimed to investigate the association between eosinophil and severe irAEs in patients receiving ipilimumab plus nivolumab therapy for RCC.

Methods

In this retrospective study, 161 patients receiving ipilimumab plus nivolumab therapy for RCC were divided into three groups based on whether they experienced <grade 2 irAEs (non-severe irAE group), ≥grade 3 irAEs (severe irAE group), or not (non-irAE group). We examined the proportion of eosinophils before and 2 weeks after treatment (baseline and 2-week samples, respectively).

Results

Although the eosinophil in the baseline samples did not differ between the severe irAE and non-irAE groups (2.8% vs. 2.5%, P = 0.75), regarding the 2-week samples, the eosinophil was significantly higher in the severe irAE group (mean, 6.6% vs. 3.3%; P < 0.05). Multivariate analysis showed that an eosinophil of ≥3.0% was a risk factor for severe irAEs (odds ratio, 6.01). Median progression-free survival (mPFS), mPFS from the start of ipilimumab plus nivolumab therapy to second-line therapy (mPFS2), and median overall survival (mOS) were the shortest in the non-irAE group. Although the mPFS did not differ between the severe and non-severe irAE groups (9.2 vs 14.2 months, P = 0.45), notably, mPFS2 and mOS in the former group tended to be shorter than those in the latter group (mPFS2: 29.2 vs not reached, P = 0.10; mOS: 36.9 vs 52.3 months, P = 0.06).

Discussion

An increased eosinophil 2 weeks after ipilimumab plus nivolumab therapy may be a predictor of severe irAEs, which are associated with poor prognoses, compared with non-severe irAEs among patients with RCC. We provide a novel rationale for the importance of monitoring eosinophil counts for the early detection of severe irAEs.
Integrated single-cell and bulk transcriptome analysis of R-loop score-based signature with regard to immune microenvironment, lipid metabolism and prognosis in HCC
Authors: Chen Long , Yang Houzhi , Wei Xianfu , Liu Jianchao , Han Xiuxin , Zhang Chao , Liu Yongheng , Zhang Yan , Xu Yao , Li Yiqin , Wang Guowen , Feng Jinyan
Published: January 2025

Background

Hepatocellular carcinoma (HCC) is one of the most prevalent causes of cancer-related morbidity and mortality worldwide. Late-stage detection and the complex molecular mechanisms driving tumor progression contribute significantly to its poor prognosis. Dysregulated R-loops, three-stranded nucleic acid structures associated with genome instability, play a key role in the malignant characteristics of various tumors. However, the detailed role and mechanism of R-loops in HCC progression remain elusive and require further exploration. This study aimed to construct an R-loop scoring signature centered on prognosis and lipid metabolism, thereby enhancing our understanding of HCC progression and identifying potential therapeutic targets.

Methods

In this study, we utilized the single-cell RNA-sequencing (scRNA-seq) data from HCC patients (GSE149614 and CRA002308) to construct an R-loop scoring model based on the identified R-loop regulator genes (RLRGs) related to HBV infection through WGCNA analysis. We also explored the tumor microenvironment and intercellular communication related to R-loop score. Additionally, a prognostic risk model based on the fatty acid metabolism-associated RLRGs was constructed using data from the TCGA database, and its association with immune infiltration, mutations, and drug sensitivity was analyzed. In vitro and in vivo experiments were performed to investigate the role of RLRG CLTC in lipid metabolism and HCC progression.

Results

Using scRNA-seq data from HCC, we established an R-loop scoring model based on identified RLRGs related to HBV infection. Moreover, the more suppressive tumor immune microenvironment and stronger intercellular communication were displayed in malignant cells with high R-loop scores. The cell trajectory and cellular metabolism analysis exhibited a significant association between lipid metabolism and RLRGs. Additionally, we constructed a prognostic risk model consisting of 8 RLRGs related to fatty acid metabolism, which effectively evaluated the prognostic value, status of tumor immune microenvironment, gene mutations, and chemotherapeutic drug sensitivity for HCC patients. Notably, validation experiments suggested that CLTC could regulate lipid metabolism through R-loop formation and facilitate tumor progression in HCC.

Conclusion

Collectively, our study proposes an R-loop scoring model associated with tumor immune microenvironment, lipid metabolism and prognostic value. CLTC, an R-loop regulator, emerges as a promising prognostic biomarker and therapeutic target, offering new insights into potential treatment strategies for HCC patients.
Evolutionary patterns and research frontiers in autophagy in podocytopathies: a bibliometric analysis
Authors: Liu Feng , Xu Ziyu , Chen Gaijie , Xu Xiaojing , Cao Huixia , Chen Jiefang
Published: January 2025

Introduction

Podocytopathies are a uniquely renal disease syndrome, in which direct or indirect podocyte injury leads to proteinuria or nephrotic syndrome. Of the many factors that contribute to podocytopathies, the abnormal regulation of autophagy, such insufficient or excessive autophagy levels, have been proposed to play a significant role in the occurrence and development of podocytopathies. However, there still has been a lack of systematic and comparative research to elucidate exact role of autophagy in podocytopathies and its current research status. This study aims to utilize bibliometric analysis to clarify the role of autophagy in the pathogenesis of podocytopathies, analyze the research focus in this area, as well as explore the future research trends.

Methods

We retrieved original articles and review papers with respect to autophagy in podocytopathies research published between the year 2008 and 2022 from the Web of Science Core Collection (WOSCC). Then, VOSviewer and CiteSpace software were employed to reveal the leading subjects and generate visual maps of countries/regions, organizations, authors, journals, and keyword networks in this field.

Results and discussion

A total of 825 publications regarding autophagy in podocytopathies published between 2008 and 2022 were included, with China contributing the most followed by the United States and Japan. Professor Koya Daisuke, Professor He Qiang, and Professor Jin Juan are the most prolific researchers in this field. Oxidative stress, the NLRP3 inflammasome, and therapeutic targets were the knowledge base for the research in this special field. Taken together, this bibliometric analysis helps us reveal the current research hotspots and guide future research directions, which provides a reference for scholars to further investigate the role of autophagy in podocytopathies as well as conduct clinical trial with autophagy regulators in podocytopathies.
Opsoclonus-myoclonus syndrome in the course of teratoma: a case report
Authors: Szczupak Mateusz , Kobak Jacek , Wiśniewska Anna , Kosydar-Bochenek Justyna , Jamro Arkadiusz , Krupa-Nurcek Sabina
Published: January 2025

Opsoclonus-myoclonus syndrome (OMS) is a rare neurological inflammatory disease of paraneoplastic, parainfectious or idiopathic origin. It is manifested by the occurrence of opsoclonus, myoclonus, ataxia, as well as behavioral and sleep disorders. The incidence is estimated at 1/5,000,000 people. This syndrome is usually immune-mediated and may be the first manifestation of cancer as a paraneoplastic syndrome, most often occurring in the course of breast, ovarian or lung cancer. Here we show a case of a 20-year-old woman with symptomatic opsoclonus-myoclonus syndrome in the course of teratoma. A brief review of the literature was conducted to determine the diagnostic route and treatment of this rare condition. As a result, it has been shown that the only method of treatment for OMS syndrome is the removal of the neoplastic lesion.
Long-term adoption of plow tillage and green manure improves soil physicochemical properties and optimizes microbial communities under a continuous peanut monoculture system
Authors: Yao Yunfeng , Zhu Rongyv , Li Xiangdong , Hu Guoqing , Dong Yuanjie , Liu Zhaoxin
Published: January 2025

Continuous monocropping of peanuts (Arachis hypogaea L.) often results in yield decline and soil degradation. The combination of green manure (GM) with tillage practices has been proposed as a sustainable strategy to maintain high crop productivity and improve soil quality. This study investigates the long-term effects of 8 years of GM application combined with plow tillage on soil microbial communities and physicochemical properties under a peanut monocropping system. Treatments included: (i) no tillage (NT); (ii) plow tillage before the winter fallow period (PT); and (iii) growing ryegrass (Lolium perenne L.) during the winter period and applying it as GM before planting next-stubble peanut (PTGM). It was found that both PTGM and PT remarkably decreased the average bulk density (BD), while elevated the mean soil porosity (SP) in 0–30 cm soil layer. Moreover, PTGM significantly increased available potassium (AK), available phosphorus (AP), total nitrogen (TN), and soil organic matter (SOM). Peanut pod yields in the PTGM treatment were 14.1 and 7.2% higher compared to the PT and NT treatments, respectively. Additionally, PTGM could promote shifts in soil bacteria compositions, increasing the abundance of Actinobacteria and Firmicutes while reducing that of Chloroflexi. For fungal abundances, PTGM elevated the abundances of Ascomycota and Basidiomycote. Redundancy analysis demonstrated that SOM, TN, AK, and AP were positively related to dominant flora of fungi and bacteria in PTGM, while negatively related to dominant flora of fungi and bacteria in NT. Overall, tillage practices have the potential to reshape the microbial community during the peanut growing season, primarily due to the influence of SOM, TN, and AP content in shaping microbial diversity and composition. Our study highlights that plow tillage combined with GM application may serve as an effective tillage practice in the future to mitigate continuous cropping obstacles by modulating soil microbial communities, improving soil nutrients and fertility, and enhancing crop productivity.
Comparison of an AI-based mobile pupillometry system and NPi-200 for pupillary light reflex and correlation with glaucoma-related markers
Authors: Jaworski Damian , Suwała Karolina , Kaluzny Bartlomiej J , Kaluzny Jakub J.
Published: January 2025

Introduction

Glaucoma is a leading cause of blindness, often progressing asymptomatically until significant vision loss occurs. Early detection is crucial for preventing irreversible damage. The pupillary light reflex (PLR) has proven useful in glaucoma diagnosis, and mobile technologies like the AI-based smartphone pupillometer (AI Pupillometer) offer a promising solution for accessible screening. This study assesses the reliability of the AI Pupillometer in detecting glaucoma.

Methods

In Experiment 1, 20 healthy participants were assessed using both the AI Pupillometer and the NPi-200 device to evaluate equivalence in measuring PLR. Each eye underwent three trials. Experiment 2 included 46 participants, 24 with primary open-angle glaucoma (POAG) and 22 healthy controls. PLR measurements from the AI Pupillometer were correlated with structural and functional ocular parameters. An additional study expanded the sample to 387 participants (103 glaucoma patients, 284 controls), focusing on differential pupillometry parameters to minimize ambient light interference.

Results

In Experiment 1, the AI Pupillometer demonstrated strong correlations with the NPi-200 in key parameters like initial pupil size (r = 0.700), constricted pupil size (r = 0.755), and constriction velocity (r = 0.541), confirming its reliability. In Experiment 2, although no statistically significant differences in light-corrected PLR parameters were found between groups, glaucoma patients had a marginally higher constricted pupil size (p = 0.1632). Significant correlations were observed between pupillometry and advanced ocular imaging results, notably between constriction amplitude and visual field loss. The additional study revealed significant differences in constriction amplitude (p = 0.014) and relative pupil size change (p = 0.0072) between glaucoma patients and controls, reinforcing the AI Pupillometer’s diagnostic potential.

Conclusion

This study confirms the AI Pupillometer as a reliable, accessible tool for glaucoma screening. Mobile diagnostics could enhance early detection, improving outcomes for glaucoma patients.
Acute beneficial effects of a functional energy shot on cognitive performance and mood states during cognitively demanding task performance: a randomized, double-blind, placebo-controlled, crossover trial
Authors: O’Shea Olivia K. , Lawley Nathan , Azzopardi Anna , Gutkowski Allison , Niedziela Michelle Murphy , Horn Rachel , Kennedy David O. , Adamson Jason
Published: January 2025

Introduction

Functional beverages are increasingly popular but it is important to validate their purported effects through research. The aim of the current study was to investigate the effects of a new functional energy shot on cognitive performance and mood states in healthy adults, with a focus on measuring mental energy enhancement and attenuation of negative effects associated with extended performance of mentally demanding tasks.

Methods

This study was a randomized, double-blind, placebo-controlled, crossover trial. Thirty-seven healthy males and females, aged 18–30 years, consumed a functional energy shot (Ryde: Energize) or placebo on separate testing occasions one-week apart. Participants completed cognitive and mood assessments pre-dose, and then 30 minutes post-dose over the course of approximately 2 hours. The functional energy shot contained caffeine, ginseng, vitamins and taurine, while the placebo shot was matched for flavor but did not contain these additional ingredients.

Results

Use of the functional energy shot was associated with significant improvements over placebo in cognitive performance, as measured by the Cognitive Demand Battery, with enhanced global performance, task-specific accuracy and speed across repeated assessments. Additionally, the shot mitigated negative effects associated with extended cognitive tasks, reducing perceived mental fatigue and increasing perceived alertness and energy. Working memory tasks showed faster performance post-consumption, and mood assessments revealed positive effects on vigor, fatigue and overall mood disturbance.

Discussion

These results indicate wide cognitive and mood effects of this functional energy shot, potentially attributable to synergistic combination of active ingredients.

Clinical trial registration

clinicaltrials.gov, identifier NCT06384586.
Long term outcomes associated with the use of perioperative systemic chemotherapy on low grade appendiceal mucinous neoplasms with pseudomyxoma peritonei treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy
Authors: Ruff Samantha M. , Kasumova Gyulnara , Palavalli Manoj , Eng Oliver S. , Lambert Laura , Clarke Callisia , Patel Sameer , Veerapong Jula , Fournier Keith , Abbott Daniel , Staley Charles , Grotz Travis , Johnston Fabian , Raoof Mustafa , Dineen Sean , Cloyd Jordan M. , Kim Alex C.
Published: January 2025

Introduction

Low grade appendiceal mucinous neoplasms (LAMN) are indolent tumors that lack invasive potential but may present as pseudomyxoma peritonei. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) significantly improves both overall and recurrence free survival. While systemic chemotherapy is generally considered ineffective for LAMN, little literature is available to support this notion. We evaluated outcomes for individuals with LAMN who did and did not receive systemic chemotherapy in combination with CRS+HIPEC.

Methods

A multicenter retrospective cohort study was performed using the US HIPEC Collaborative that included patients with LAMN who underwent CRS+HIPEC. The overall survival (OS) and recurrence-free survival (RFS) of patients who did and did not receive systemic chemotherapy were compared. Survival and variables associated with survival were evaluated with the Kaplan-Meier analysis and cox regression, respectively.

Results

Among the 529 included patients with LAMN, 63 (11.9%) received systemic chemotherapy and CRS+HIPEC, while 466 (88.1%) were treated with only CRS+HIPEC. Patients selected for systemic chemotherapy had a higher burden of disease (mean peritoneal cancer index: 18.8 +/- 8.6 versus 14.3 +/- 8.8, p<0.001). Patients who were not treated with chemotherapy had better mean OS and RFS (OS: 104.3 +/- 6.2 months, RFS: 84.9 +/- 6.6 months) compared to those who underwent systemic chemotherapy (OS: 70.2 +/- 6.8 months, RFS: 38 +/- 5.9 months, p<0.001). Increasing pre-operative CEA level (HR 1.012, p<0.001), higher completeness of cytoreduction score (reference CCR 0, CCR2 HR 34.175, p=0.001 and CCR3 HR 52.041, p=0.001), and treatment with systemic chemotherapy (HR 4.196, p=0.045) were associated with worse OS.

Conclusions

In this multicenter retrospective study, the receipt of perioperative chemotherapy was associated with worse long-term outcomes among patients with LAMN undergoing CRS-HIPEC. Systemic chemotherapy may lead to patient deconditioning and contribute to worse long-term outcomes. It should not be recommended outside of a clinical trial.
Deciphering the oncogenic network: how C1QTNF1-AS1 modulates osteosarcoma through miR-34a-5p and glycolytic pathways
Authors: Zhang Yu , Lun Hailong , Zhu Naiqiang , Yang Ning , Ding Kaikai , Chen Bin , Chang Chengbing , Gu Haipeng , Liu Yanqi
Published: January 2025

Introduction

Osteosarcoma (OS), a prevalent metastatic cancer among young individuals, is associated with a grim prognosis. Long non-coding RNAs (lncRNAs), including C1QTNF1-AS1, are pivotal regulators of cancer cell proliferation and motility. As an oncogene, C1QTNF1-AS1 is implicated in various tumor types, such as colorectal, pancreatic, hepatocellular carcinomas, and OS. The aim of this study was to investigate the functions and underlying mechanisms of C1QTNF1-AS1 in the progression of osteosarcoma.

Methods

This investigation focused on elucidating the functional roles and mechanisms of C1QTNF1-AS1 in OS cells. Bioinformatics tools were utilized to identify the interaction between microRNA miR-34a-5p and C1QTNF1-AS1, as well as the targeting of LDHA and PDK3 by miR-34a-5p. Dual-luciferase reporter assays and RNA immunoprecipitation were employed to validate these interactions. Expression profiles of C1QTNF1-AS1, miR-34a-5p, LDHA, and PDK3 in osteosarcoma cells were analyzed using RT-PCR and western blot analyses, revealing their intricate relationships. The impact of these molecules on OS cell proliferation, invasion, and migration was assessed through CCK-8, Transwell, and Cell scratch assay. Moreover, the effects on aerobic glycolysis in OS cells were examined by quantifying ATP levels, lactate production, glucose uptake capacity, and the extracellular acidification rate.

Results

The findings indicated a significant decrease in C1QTNF1-AS1 expression levels in OS cells compared to normal osteoblasts. A parallel downregulation trend of miR-34a-5p was also observed in OS cells. Silencing C1QTNF1-AS1 led to a marked upregulation of LDHA and PDK3 in OS cells, which was partially attenuated by miR-34a-5p mimics. Functional evaluations demonstrated that suppression of C1QTNF1-AS1 accelerated OS cell growth, motility, invasiveness, and the Warburg effect. Conversely, the overexpression of miR-34a-5p mitigated these stimulatory effects, suggesting a regulatory role in modulating OS progression.

Discussion

Our research emphasizes the critical role of C1QTNF1-AS1 in the pathogenesis of osteosarcoma (OS). We discovered that the downregulation of C1QTNF1-AS1 indirectly upregulates the expression of LDHA and PDK3 by suppressing miR-34a-5p, which functions as a regulator of the Warburg effect. This cascade of events promotes OS progression by enhancing glycolytic metabolism and supplying energy for cancer cell growth, migration, and invasion. These findings suggest a potential therapeutic target and highlight the importance of understanding the regulatory network involving lncRNAs in cancer metabolism and progression.
DET induces apoptosis and suppresses tumor invasion in glioma cells via PI3K/AKT pathway
Authors: Zhao Rui , Wang Mengran , Wu Zeyu , Zhao Panpan , Dong Huiling , Su Yue , Zhao Chenghui , Qi Min , Ling Shizhang , Jiang Xiaochun
Published: January 2025

Introduction

Gliomas, particularly glioblastomas (GBM), are highly aggressive with a poor prognosis and low survival rate. Currently, deoxyelephantopin (DET) has shown promising anti-inflammatory and anti-tumor effects. Using clinical prognostic analysis, molecular docking, and network pharmacology, this study aims to explore the primary targets and signaling pathways to identify novel GBM treatment approaches.

Methods

Using PharmMapper, the chemical structure of DET was examined for possible targets after being acquired from PubChem. GBM-related targets were obtained through multi-omics approaches. A protein-protein interaction (PPI) network was constructed using Cytoscape and STRING, and target binding was evaluated through molecular docking. Enrichment analysis was conducted using Metascape. The effects of DET on GBM cell invasion, apoptosis, and proliferation were assessed through in vitro assays, including Transwell, EDU, CCK8, and flow cytometry. Western blot analysis was performed to examine the components of the PI3K/AKT signaling pathway.

Results

Among the sixty-four shared targets identified, JUN and CCND1 were the most frequently observed. Enrichment analysis demonstrated that DET influenced the MAPK and PI3K/AKT signaling pathways. In Transwell assays, DET significantly inhibited the invasive behavior of glioma cells. Western blot analysis further confirmed the downregulation of EGFR, JUN, and PI3K/AKT.

Conclusion

DET inhibits GBM cell invasion, proliferation, and apoptosis via modulating the PI3K/AKT signaling pathway, highlighting its potential as a novel therapeutic strategy for GBM treatment.
Endothelin receptor antagonists (ERAs) can potentially be used as therapeutic drugs to reduce hypertension caused by small molecule tyrosine kinase inhibitors (TKIs)
Authors: He Qingjian , Lin Junling , Mo Chanjuan , Li Guodong , Lu Jianzhong , Sun Qiyin , Cao Lijun , Gan Haojian , Sun Quan , Yao Jiafang , Lian Shengyi , Wang WenJuan
Published: January 2025

The emergence of targeted anti-tumor drugs has significantly prolonged the lifespan and improved the prognosis of cancer patients. Among these drugs, vascular endothelial growth factor (VEGF) inhibitors, particularly novel small molecule tyrosine kinase inhibitors (TKIs), are extensively employed as VEGF inhibitors; however, they are also associated with a higher incidence of complications, with hypertension being the most prevalent cardiovascular toxic side effect. Currently, it is widely accepted that TKIs-induced hypertension involves multiple mechanisms including dysregulation of the endothelin (ET) axis, reduced bioavailability of nitric oxide (NO), imbalance in NO-ROS equilibrium system, vascular rarefaction, and activation of epithelial sodium calcium channels; nevertheless, excessive activation of ET system appears to be predominantly responsible for this condition. Moreover, studies have demonstrated that ET plays a pivotal role in driving TKIs-induced hypertension. Therefore, this review aims to explore the significance of ET in the pathogenesis of hypertension induced by targeted anti-tumor drugs and investigate the potential therapeutic value of endothelin antagonists in managing hypertension caused by targeted anti-tumor drugs.
Population pharmacokinetics and dosing optimization of imipenem in Chinese elderly patients
Authors: Wang Jing , Fang Qiu , Luo Xuemei , Jin Lu , Zhu Huaijun
Published: January 2025

Objectives

To assess the pharmacokinetics and pharmacodynamics of imipenem in a retrospective cohort of hospitalized Chinese older patients.

Methods

A population pharmacokinetic (PPK) model was constructed utilizing a nonlinear mixed-effects modeling approach. The final model underwent evaluation through bootstrap resampling and visual predictive checks. Additionally, a population pharmacokinetic and pharmacodynamic analysis was conducted employing Monte Carlo simulations to investigate the impact of commonly used dosing regimens (0.25 g every 6 h, 0.5 g every 6 h, 0.5 g every 8 h, 1 g every 6 h, 1 g every 8 h, and 1 g every 12 h) on the likelihood of achieving the target therapeutic outcomes.

Results

A total of 370 observations available from 142 patients were incorporated in the PPK model. A two-compartment PPK model with linear elimination best predicted the imipenem plasma concentrations, with the creatinine clearance as a significant covariate of clearance. Typical estimates for clearance, inter-compartmental clearance, central and peripheral volume were 13.1 L·h−1, 11.9 L·h−1, 11.7 L, 29.3 L, respectively.

Conclusion

The pharmacokinetics of imipenem in elderly patients were effectively characterized by the established PPK model, which includes creatinine clearance as a key covariate. This research will enhance our understanding of imipenem elimination and support precision dosing in this patient demographic.
Odyssey of environmental and microbial interventions in maize crop improvement
Authors: Singh Alok Kumar , Srivastava Alok Kumar , Johri Parul , Dwivedi Manish , Kaushal Radhey Shyam , Trivedi Mala , Upadhyay Tarun Kumar , Alabdallah Nadiyah M. , Ahmad Irfan , Saeed Mohd , Lakhanpal Sorabh
Published: January 2025

Maize (Zea mays) is India’s third-largest grain crop, serving as a primary food source for at least 30% of the population and sustaining 900 million impoverished people globally. The growing human population has led to an increasing demand for maize grains. However, maize cultivation faces significant challenges due to a variety of environmental factors, including both biotic and abiotic stresses. Abiotic stresses such as salinity, extreme temperatures, and drought, along with biotic factors like bacterial, fungal, and viral infections, have drastically reduced maize production and grain quality worldwide. The interaction between these stresses is complex; for instance, abiotic stress can heighten a plant’s susceptibility to pathogens, while an overabundance of pests can exacerbate the plant’s response to environmental stress. Given the complexity of these interactions, comprehensive studies are crucial for understanding how the simultaneous presence of biotic and abiotic stresses affects crop productivity. Despite the importance of this issue, there is a lack of comprehensive data on how these stress combinations impact maize in key agricultural regions. This review focuses on developing abiotic stress-tolerant maize varieties, which will be essential for maintaining crop yields in the future. One promising approach involves the use of Plant Growth-Promoting Rhizobacteria (PGPR), soil bacteria that colonize the rhizosphere and interact with plant tissues. Scientists are increasingly exploring microbial strategies to enhance maize’s resistance to both biotic and abiotic stresses. Throughout the cultivation process, insect pests and microorganisms pose significant threats to maize, diminishing both the quantity and quality of the grain. Among the various factors causing maize degradation, insects are the most prevalent, followed by fungal infections. The review also delves into the latest advancements in applying beneficial rhizobacteria across different agroecosystems, highlighting current trends and offering insights into future developments under both normal and stress conditions.
Conceptual framework of coaches’ decision-making in conventional sports
Authors: Kolar Edvard , Biloslavo Roberto , Pišot Rado , Veličković Saša , Tušak Matej
Published: January 2025

Introduction

A coach’s managerial and pedagogical tasks in the sports training process constitute the substantive core of their work, while decision-making serves as the fundamental method underpinning these tasks. Some decisions made by coaches result from deliberate, analytical thinking, which involves extensive information gathering, analysis, and discussion. Others, however, are made quickly and spontaneously, triggered by unforeseen situations during training or competition that demand immediate action. Consequently, the purpose of this study is to develop a conceptual framework for understanding coaches’ decision-making behavior in conventional sports. This framework aims to establish appropriate relationships between the various decisions coaches make during the training process and theoretical concepts related to decision-making, both in general and within the coaching context.

Methods

To design the research, we used the methodology of a conceptual paper and a “model paper” approach, which seeks to build a theoretical framework that predicts relationships between distinct research concepts and scientific disciplines, aiming to integrate them into a cohesive model of coaches’ decision-making behavior.

Results

The proposed conceptual framework encompasses a comprehensive range of situations that may arise during the sports training process and potential ways to address them. This framework identifies different types of decisions and characteristics associated with coaches’ decision-making behavior. It incorporates various sport-specific and general theories of decision-making and cognitive functioning to offer a deeper understanding of how coaches process and execute decisions in diverse contexts.

Discussion

The developed conceptual framework outlines three primary types of decisions—strategic, tactical, and operational—each playing a distinct role in the broader sports training process. These decisions are based on different cognitive processes, which manifest in varied decision-making behaviors and are reinforced by specific leadership styles. The practical value of this framework lies in its potential application for selecting appropriate experts to address the diverse decision-making scenarios encountered in sports training. This ensures the alignment of decision-making styles with the requirements of specific training situations, thereby enhancing the effectiveness and outcomes of the coaching process.
Effectiveness of a home-based computerized cognitive training in Parkinson's disease: a pilot randomized cross-over study
Authors: Tagliente Serena , Minafra Brigida , Aresta Simona , Santacesaria Paola , Buccoliero Andrea , Palmirotta Cinzia , Lagravinese Gianvito , Mongelli Davide , Gelao Christian , Macchitella Luigi , Pazzi Stefania , Scrutinio Domenico , Baiardi Paola , Battista Petronilla
Published: January 2025

Introduction

Cognitive symptoms are common in Parkinson's Disease (PD), and digital interventions like telerehabilitation other an accessible way to manage these symptoms. This study aimed to assess the effectiveness of a Home-Based Computerized Cognitive Training (HB-CCT) program in individuals with PD using a pilot randomized cross-over design.

Methods

Twenty-five participants (mean age 69.32 ± 7.21 years, mean MDS-UPDRS III 33.76 ± 14.25) with PD and mild cognitive impairment were enrolled. They underwent neuropsychological assessments at three time points (5-week intervals): Baseline, after the HB-CCTi, and after Standard Care. The HB-CCT consisted of the Neurotablet® platform that was used to target cognitive domains such as Attention, Memory, Perception, Executive Functioning and Language. All participants completed both the Neurotablet intervention and Standard Care blocks in a randomized order. After a Shapiro-Wilk test, non-parametric repeated measures analyses of variance (Friedman's test) and post-hoc comparisons corrected with the Benjamini-Hochberg approach were performed to compare the effects on primary and secondary cognitive outcomes over experimental intervention and Standard Care.

Results

The results from the Friedman analysis revealed significant improvements in Word List Immediate Recall, Digit Span Forward and Complex Figure Recall (all p < 0.001) following the HB-CCT, compared to the Baseline. Additionally, Naming performance showed significant improvement after the HB-CCT (p = 0.02). Significant differences were also observed when comparing the HB-CCT with Standard Care, with improved performance in TMT-A (p = 0.02), Phonemic Fluency (p < 0.01), and Digit Span Forward (p < 0.01).

Discussion

These findings suggest that HB-CCT via Neurotablet can effectively enhance specific cognitive abilities in PD, supporting the role of digital, home-based interventions as feasible strategies to mitigate cognitive decline.
Integrated health and nutrition approaches to school feeding: maximising future human capital in Latin America and the Caribbean
Authors: Irizarry Laura M. , Tamagnan Marie Evane , Mejía Carla , Kessler Heidi , Kohnstamm Sarah Grundahl , Baldi Giulia
Published: January 2025

Integrated health and nutrition packages in schools have been shown to be a cost-effective approach to support children’s well-being and academic achievement; yet few countries adequately invest in promoting such integration. School feeding programmes in Latin America are among the best-established, with some of the largest scale and coverage in the world. National School Meal programmes in Latin America and the Caribbean benefit over 80.3 million children and adolescents in the region. This paper seeks to determine the level of integration of complementary activities to school meal programmes in the region by examining their determinant factors: objectives, complementary services, governing regulatory frameworks, and monitoring and evaluation mechanisms. Our review reveals that although most governments offer school meals together with at least one complementary health and/or nutrition intervention, multisectoral commitment and investment is lacking. Under the premise that most school meal programmes in Latin America and the Caribbean have the potential to maximize their impact by providing integrated packages that meet children’s health and nutrition needs, we provide recommendations and raise considerations for the revision of programmatic guidance and policies moving forward. This analysis is relevant to countries internationally and calls for a comparable analysis to be carried out to promote a wide-reaching exchange on the integration of complementary activities to school feeding programmes globally.