bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary Cranial Vault Lymphoma Misdiagnosed as Atypical Meningioma: A Case Report
Authors: Ebinama Ugochi , Khan Hina , Akula Vinita , Rios Adan
Published: September 2023

Primary non-Hodgkin's lymphoma of the bone is an unusual presentation of Hodgkin's lymphoma, with primary cranial vault lymphoma (PCVL) being the rarest of bone lymphomas. We describe a case of an immunocompetent elderly patient with new onset gait imbalance and cognitive delays. Brain imaging showed a large extra-axial mass with osseous invasion. An initial misdiagnosis of meningioma led to delays in management. Further work up included a brain magnetic resonance image showing a large right transcalvarial parietal mass. The mass was surgically removed, and pathology revealed B-cell lymphoma with low-grade features thus establishing the diagnosis of PCVL. Management included subtotal resection of the tumor followed by adjuvant radiation therapy. The patient has achieved a durable response for over a year. Meningioma and PCVL have similar imaging and clinical presentations. This case report addresses differing features of the tumors and explores therapeutic options for management of PCVL.
Characterization of the Components and Functional Properties of a Plasma-Derived Fibrin Sealant
Authors: Ramaiola Ilaria , Lopez Laura , Moron Manuel , Maduell Pau , López Maite , Marzo Nuria , Grancha Salvador
Published: September 2023

Background

The activity and purity of Fibrin Sealant Grifols are described in this article. This fibrin sealant contains two components (fibrinogen and thrombin) that mimic the final stages of clotting. Fibrin sealants are primarily used as an adjunct to hemostasis for mild to moderate surgical bleeding in adults when standard surgical techniques are ineffective or impractical.

Objective

The aim of these studies was to assess the biochemical and functional characteristics of Fibrin Sealant Grifols.

Methods

Total protein, plasma protein impurities, and molecular forms were analyzed for both components. Clottable fibrinogen and thrombin activity were also measured. Both components were analyzed by SDS-PAGE and Western blot. The fibrin sealant clot was functionally characterized.

Results

The components had minimal contamination by other plasma proteins and no aggregates or degradation products. The fibrinogen component was almost completely clottable fibrinogen. The thrombin component contains albumin. The fibrinogen component formed a fibrin polymer and clots with tensile strength similar to literature values. The application device applied the components in a 1:1 volume ratio. Clotting time was ∼ 5 s when applied with the drip tip and nearly instantaneous when applied with the airless spray apparatus.

Conclusion

This fibrin sealant was shown to contain highly purified fibrinogen and thrombin delivered in a 1:1 volume ratio. These properties contribute to the clinical safety and efficacy of this product for many applications.
A Multifaceted Educational Intervention to Reduce Plasma Utilization
Authors: Badawi Maha A. , Algiraigri Ali , Al-Sulami Afnan J. , Abunar Anas A. , Alharbi Rami , Park Yoon Soo , Tekian Ara
Published: September 2023

Blood transfusion services maintain quality practice through adherence to guidelines but are faced with blood component wastage due to multiple factors. One factor, in particular, is poor ordering and utilization practices followed by physicians who may not be familiar with the indications and the optimal conditions for the handling of blood products. This study evaluates whether an educational intervention would help reduce ordering of plasma and improve wastage rates after thawing. The study followed a quasi-experimental pre-test post-test design. A multifaceted educational intervention was introduced at a tertiary hospital-based combining predisposing, enabling, and reinforcing activities, based on the literature of effective continuous professional development. The activities included a brief survey to evaluate participant knowledge about indications of plasma and its storage condition, a lecture, and periodic reports and reminders sent to all department heads in the hospital. Respondents to the survey and lecture attendees included physicians in adult critical care and anesthesia departments. Monthly plasma utilization and wastage rates were compared before and after introducing the intervention. Sixty physicians participated in the survey. The questions were answered correctly by less than half. After introducing the intervention, monthly plasma transfusion rates decreased; however, wastage rates did not improve. There is a knowledge gap among physicians who order plasma. The educational intervention resulted in lower plasma transfusion rates but did not affect wastage rates. Future interventions would benefit from including physicians in other departments as well as nurses.
Lipid Profile, Nutritional Status and Severity Biomarkers in Adults With Sickle Cell Anemia
Authors: Pereira Gomes Ingrid Cristiane , Costa Machado Teles João Pedro , Sousa Coelho Anny Catarina , Passos Cruz Maria Carollyne , Costa de Albuquerque Lindemberg , Carvalho Mariana Amaral , Castro dos Santos Paulo Herlan , Nolasco dos Santos Sérgio , Cipolotti Rosana
Published: September 2023

BACKGROUND

Lipid alterations have been described in sickle cell anemia (SCA), but their association with the disease severity is not fully understood and their correlation with the nutritional status of this population has not been widely studied.

OBJECTIVES

This study aimed to assess the lipid profile and its relation with the nutritional status, including anthropometric characteristics and daily macronutrient intake, and with the severity biomarkers in adults with SCA in a steady state.

DESIGN

Cross-sectional study

METHODS

This was an analytical cross-sectional study with 55 adults with SCA and 60 members of the control group. Sociodemographic, anthropometric, nutritional, and laboratory data were collected between March 2019 and June 2020. Mann–Whitney test was used to compare groups and Spearman's correlation coefficient was used to test the relation between variables.

RESULTS

The SCA group presented higher calorie, protein, and carbohydrate intake, lower levels of high-density lipoprotein-cholesterol (HDL-c), and a higher triglyceride (TG)/HDL-c ratio than the control. HDL-c showed a positive correlation with hemoglobin and hematocrit (HcT) and a negative correlation with indirect bilirubin and lactate dehydrogenase (LDH). The TG/HDL-c ratio was positively linked with reticulocyte count, LDH, and leukocyte count and negatively linked with Hb.

CONCLUSIONS

The study findings showed hypocholesterolemia in SCA and its independent correlation with macronutrient intake. The links of HDL-c and TG/HDL-c ratio with hemolysis indices indicate that they are easily accessible, low-cost markers capable of predicting SCA severity.
Adaptation of an In-Person Mind-Body Movement Program for People with Cognitive Impairment or Dementia and Care Partners for Online Delivery: Feasibility, Satisfaction and Participant-Reported Outcomes
Authors: Nicosia Francesca M. , Lee Jennifer A. , Chesney Margaret A. , Benjamin Cynthia , Lee Amanda N. , Mehling Wolf , Sudore Rebecca L. , Barnes Deborah E.
Published: September 2023

Background

Preventing Loss of Independence through Exercise (PLIÉ) is an in-person group mind-body movement program for people across the spectrum of cognitive decline and care partners (CPs).

Objective

This study developed and refined an online version called Moving Together and tested feasibility and satisfaction with an online delivery.

Methods

In Phase 1, we used qualitative methods to determine which elements of the in-person program were essential to retain for the online version and adaptations that would be needed to support the user experience. In Phase 2, we created a prototype of the online program and iteratively refined it based on user feedback. In Phase 3, we assessed feasibility of online delivery based on class attendance and program completion; we assessed satisfaction and participant-reported outcomes using a post-program evaluation survey with quantitative and qualitative components.

Results

Phase 1 findings from 27 participants (14 PLWD, 13 CPs) revealed three key considerations related to online delivery of PLIÉ: technology use, social connection as a primary motivator, and physical safety concerns. Phase 2 iterative testing among 25 participants (14 PLWD, 11 CPs) resulted in key refinements to program delivery and instructional elements; Phase 3 pilot testing included 39 participants (12 PLWD, 15 CPs, 12 MCI) who attended 75 ± 29% of 24 classes; 77% completed the 12-week program, of whom 96% rated it as excellent or good. Participant-reported outcomes included improvements in social connection, emotional well-being, physical function, cognitive function and present-centered body awareness. PLWD or MCI also reported improvements in self-concept, and CPs reported improvements in caregiving self-efficacy. The primary challenges were related to participant navigation of technology.

Conclusion

The Moving Together online program is feasible for PLWD or MCI and CPs with participants reporting high satisfaction and positive outcomes across multiple domains. Providing individual technology support is critical for the success of livestreamed, online interventions for dementia.
Multi-omics insights into the positive role of strigolactone perception in barley drought response
Authors: Daszkowska-Golec Agata , Mehta Devang , Uhrig R. Glen , Brąszewska Agnieszka , Novak Ondrej , Fontana Irene M. , Melzer Michael , Płociniczak Tomasz , Marzec Marek
Published: September 2023

Background

Drought is a major environmental stress that affects crop productivity worldwide. Although previous research demonstrated links between strigolactones (SLs) and drought, here we used barley (Hordeum vulgare) SL-insensitive mutant hvd14 (dwarf14) to scrutinize the SL-dependent mechanisms associated with water deficit response.

Results

We have employed a combination of transcriptomics, proteomics, phytohormonomics analyses, and physiological data to unravel differences between wild-type and hvd14 plants under drought. Our research revealed that drought sensitivity of hvd14 is related to weaker induction of abscisic acid-responsive genes/proteins, lower jasmonic acid content, higher reactive oxygen species content, and lower wax biosynthetic and deposition mechanisms than wild-type plants. In addition, we identified a set of transcription factors (TFs) that are exclusively drought-induced in the wild-type barley.

Conclusions

Critically, we resolved a comprehensive series of interactions between the drought-induced barley transcriptome and proteome responses, allowing us to understand the profound effects of SLs in alleviating water-limiting conditions. Several new avenues have opened for developing barley more resilient to drought through the information provided. Moreover, our study contributes to a better understanding of the complex interplay between genes, proteins, and hormones in response to drought, and underscores the importance of a multidisciplinary approach to studying plant stress response mechanisms.
Effect of intravenous dexamethasone on the duration of hyperbaric bupivacaine spinal anesthesia in lower abdominal surgery, Randomized controlled trial
Authors: Abdel-Wahab Amani H. , Abd Alla Essam S. , Abd El-Azeem Taghreed
Published: September 2023

Background

The purpose of this study was to investigate the effect of intravenous (IV) dexamethasone on the duration of hyperbaric bupivacaine spinal anesthesia.

Methods

Two hundred patients between the ages of 18 and 60, of both sexes with ASA I- II classification scheduled for lower abdominal surgery under spinal anesthesia using hyperbaric bupivacaine 0.5% were randomly divided into two groups: the dexamethasone group (Dexa group) and the control group, with 100 patients in each group. Before the administration of spinal anesthesia, the Dexa group received an intravenous infusion of 8 mg dexamethasone in 500 mL normal saline, while the control group received 500 mL normal saline only. The primary outcome of this study was to assess the effect of IV dexamethasone on the regression of hyperbaric bupivacaine spinal anesthesia. Secondary outcome measures included the total duration of sensory and motor blocks, VAS score, time of first analgesic request, total analgesic consumption within the first 24 h, and the occurrence of any side effects.

Results

The Dexa group had significantly delayed onset of 2 dermatomes regression (P < 0.001) compared to the control group. Additionally, the Dexa group had significantly longer duration of both sensory block (P = 0.01) and motor block (P < 0.001). The Dexa group had significantly longer duration until the first postoperative analgesic request (P < 0.001) and a lower incidence of side effects compared to the control group.

Conclusion

Although the intravenous administration of dexamethasone had a limited effect on the duration of hyperbaric bupivacaine spinal anesthesia, it improved postoperative VAS scores compared to the control group and decreased overall postoperative analgesic consumption. Therefore, it can be considered a valuable addition to postoperative multimodal analgesia strategies, aiming to minimize total analgesic consumption.

Clinical trial registration

ID: NCT04778189 (2/3/2021).
The value of fever assessment in addition to the Early Detection Infection Scale (EDIS). A validation study in nursing home residents in Sweden
Authors: Tingström Pia , Karlsson Nadine , Grodzinsky Ewa , Sund Levander Märta
Published: September 2023

Background

In order to improve detection of suspected infections in frail elderly there is an urgent need for development of decision support tools, that can be used in the daily work of all healthcare professionals for assessing non-specific and specific changes. The aim was to study non-specific signs and symptoms and fever temperature for early detection of ongoing infection in frail elderly, and how these correlates to provide the instrument, the Early Detection Infection Scale (EDIS), which is used to assess changes in health condition in frail elderly.

Methods

This was an explorative, prospective cohort study, including 45 nursing home residents, 76 to 99 years, in Sweden. Nursing assistants measured morning ear body temperature twice a week and used the EDIS to assess individual health condition daily for six months. The outcome comprised events of suspected infection, compiled from nursing and medical patient records. Factor analysis and multivariate logistic regression analysis were performed to analyse data.

Results

Fifteen residents were diagnosed with at least one infection during the six-month follow-up and 189 observations related to 72 events of suspected infection were recorded. The first factor analysis revealed that the components, change in cognitive and physical function, general signs and symptoms of illness, increased tenderness, change in eye expression and food intake and change in emotions explained 61% of the variance. The second factor analysis, adding temperature assessed as fever to > 1.0 °C from individual normal, resulted in change in physical function and food intake, confusion and signs and symptoms from respiratory and urinary tract, general signs and symptoms of illness and fever and increased tenderness, explaining 59% of the variance. In the first regression analysis, increased tenderness and change in eye expression and food intake, and in the second change in physical function and food intake, general signs and symptoms of illness and fever (> 1.0 °C from individual normal) and increased tenderness were significantly associated with increased risk for ongoing infection.

Conclusion

No items in the EDIS should be removed at present, and assessment of fever as > 1.0 °C from individual normal is a valuable addition. The EDIS has the potential to make it easier for first line caregivers to systematically assess changes in health condition in fragile elderly people and helps observations to be communicated in a standardised way throughout the care process. The EDIS thus contributes to ensuring that the decisions not being taken at the wrong level of care.
Dementia death rates prediction
Authors: Gaidai Oleg , Yakimov Vladimir , Balakrishna Rajiv
Published: September 2023

Background

Prevalence of dementia illness, causing certain morbidity and mortality globally, places burden on global public health. This study primary goal was to assess future risks of dying from severe dementia, given specific return period, within selected group of regions or nations.

Methods

Traditional statistical approaches do not have benefits of effectively handling large regional dimensionality, along with nonlinear cross-correlations between various regional observations. In order to produce reliable long-term projections of excessive dementia death rate risks, this study advocates novel bio-system reliability technique, that being particularly suited for multi-regional environmental, biological, and health systems.

Data

Raw clinical data has been used as an input to the suggested population-based, bio-statistical technique using data from medical surveys and several centers.

Results

Novel spatiotemporal health system reliability methodology has been developed and applied to dementia death rates raw clinical data. Suggested methodology shown to be capable of dealing efficiently with spatiotemporal clinical observations of multi-regional nature. Accurate disease risks multi-regional spatiotemporal prediction being done, relevant confidence intervals have been presented as well.

Conclusions

Based on available clinical survey dataset, the proposed approach may be applied in a variety of clinical public health applications. Confidence bands, given for predicted dementia-associated death rate levels with return periods of interest, have been reasonably narrow, indicating practical values of advocated prognostics.
Association of metabolic syndrome and its components with the risk of urologic cancers: a prospective cohort study
Authors: Jiang Runxue , Wang Xia , Li Zhi , Cai Haifeng , Sun Zhiguo , Wu Shouling , Chen Shuohua , Hu Hailong
Published: September 2023

Objective

To investigate the association between metabolic syndrome (MetS) and its components and the risk of developing urologic cancers.

Methods

This study included 101,510 observation subjects from May 2006 to December 2007. The subjects received questionnaires and were subjected to clinical and laboratory examinations to collect data on baseline population characteristics, waist circumference (WC), blood pressure (BP), blood glucose, blood lipids, lifestyle, and past disease history. Finally, follow-up was conducted from the date of recruitment to December 31, 2019. Cox proportional hazards modelling was applied to analyze the association between MetS and its components and the risk of developing urologic cancers.

Results

A total of 97,975 observation subjects met the inclusion criteria. The cumulative follow-up period included 1,209,178.65 person-years, and the median follow-up time was 13.03 years. During the follow-up period, 485 cases of urologic cancers (165 cases of kidney cancer, 134 cases of prostate cancer, 158 cases of bladder cancer, and 28 cases of other urologic cancers) were diagnosed. The log-rank test results for the cumulative incidences of urologic cancer, kidney cancer, and prostate cancer indicated significant (P < 0.01) differences between the MetS and non-MetS groups (0.70% vs. 0.48%, 0.27% vs. 0.15%, and 0.22% vs. 0.13%, respectively). Compared to the non-MetS group, the risk of developing urologic [HR (95% CI) = 1.29 (1.08–1.55)], kidney [HR (95% CI) = 1.74 (1.28–2.37)], and prostate [HR (95% CI) = 1.47 (1.04–2.07)] cancers was significantly higher in the MetS group. In the MetS group, elevated BP increased the risk of developing of urologic cancer [HRs (95% CI) = 1.35 (1.10–1.66)] and kidney cancer [HR (95% CI) = 1.74 (1.21–2.51)], while central obesity increased the risk of developing prostate cancer [HR (95% CI) = 1.68 (1.18–2.40)].

Conclusions

MetS increased the risk of developing urologic, kidney, and prostate cancers but had no association with the development of bladder cancer.
Satisfaction and self-confidence among nursing students with simulation learning during COVID-19
Authors: Alsadi Mohammad , Oweidat Islam , Khrais Huthaifah , Tubaishat Ahmad , Nashwan Abdulqadir J.
Published: September 2023

Aim

This survey aimed to investigate nursing students’ satisfaction and self-confidence in simulation in education during the COVID-19 pandemic. Along with comparing these levels based on selected students’ characteristics.

Design

A cross-sectional survey.

Methods

The survey was conducted at the faculty of nursing of a private university in Jordan. Students’ satisfaction and self-confidence levels in simulation learning were measured using the National League for Nursing (NLN) Student Satisfaction and Self-confidence in Learning Scales.

Results

A total of 138 undergraduate nursing students participated in the survey. Students’ satisfaction levels and self-confidence in simulation learning were lower (just above the scale’s midpoint) than scores reported in similar surveys. The lowest student ratings were reported as “the variety of learning activities that can be done using simulation” and “the self-confidence to develop the needed skills and knowledge to be used in real clinical settings”. The results also indicated that as students’ progress in the bachelor’s degree program, they develop higher levels of self-confidence in simulation-based learning.

Conclusions

Nursing students’ experience of simulation learning was observed to be negatively affected by the COVID-19 pandemic. High-fidelity simulation, in particular, among other simulation modalities, can be more beneficial in similar situations. Education stakeholders are invited to invest in the resources of high-fidelity simulation to maximize its benefits and help in the recovery phase after the pandemic.
Incident low muscle mass is associated with greater lung disease and lower circulating leptin in a tobacco-exposed longitudinal cohort
Authors: Zou Richard H. , Nouraie S. Mehdi , Karoleski Chad , Zhang Yingze , Sciurba Frank C. , Forman Daniel E. , Bon Jessica
Published: September 2023

Background

Muscle loss is prevalent in chronic obstructive pulmonary disease (COPD). Prior studies evaluating musculoskeletal dysfunction in COPD have focused on individuals with baseline low muscle mass. Currently, there is limited data evaluating clinical characteristics and outcomes associated with progression to incident low muscle mass in a tobacco-exposed cohort of individuals with baseline normal muscle mass.

Methods

We evaluated 246 participants from a single-center longitudinal tobacco-exposed cohort with serial spirometry, thoracic imaging, dual energy x-ray absorptiometry (DXA) measurements, walk testing, and plasma adipokine measurements. DXA-derived fat free mass index (FFMI) and appendicular skeletal mass index (ASMI) were used as surrogates for muscle mass. Participants with incident low muscle mass (LM) at follow-up were characterized by FFMI < 18.4 kg/m2 in males and < 15.4 kg/m2 in females and/or ASMI < 7.25 kg/m2 in males and < 5.67 kg/m2 in females.

Results

Twenty-five (10%) participants progressed to incident low muscle mass at follow-up. At baseline, the LM subgroup had greater active smoking prevalence (60% v. 38%, p = 0.04), lower FFMI (17.8 ± 1.7 kg/m2 v. 19.7 ± 2.9 kg/m2, p = 0.002), lower ASMI (7.3 ± 0.9 kg/m2 v. 8.2 ± 1.2 kg/m2, p = 0.0003), and lower plasma leptin (14.9 ± 10.1 ng/mL v. 24.0 ± 20.9 ng/mL, p = 0.04). At follow-up, the LM subgroup had higher COPD prevalence (68% v. 43%, p = 0.02), lower FEV1/FVC (0.63 ± 0.12 v. 0.69 ± 0.12, p = 0.02), lower %DLco (66.5 ± 15.9% v. 73.9 ± 16.8%, p = 0.03), and higher annual rate of FFMI decline (-0.17 kg/m2/year v. -0.04 kg/m2/year, p = 0.006). There were no differences in age, gender distribution, pack years smoking history, or walk distance.

Conclusions

We identified a subgroup of tobacco-exposed individuals with normal baseline muscle mass who progressed to incident DXA-derived low muscle mass. This subgroup demonstrated synchronous lung disease and persistently low circulating leptin levels. Our study suggests the importance of assessing for muscle loss in conjunction with lung function decline when evaluating individuals with tobacco exposure.
Sirt6 enhances macrophage lipophagy and improves lipid metabolism disorder by regulating the Wnt1/β-catenin pathway in atherosclerosis
Authors: Wang Tingting , Cheng Zheng , Zhao Ran , Cheng Jin , Ren He , Zhang Pengke , Liu Pengyun , Hao Qimeng , Zhang Qian , Yu Xiaolei , Sun Dongdong , Zhang Dongwei
Published: September 2023

Lipid metabolism disorders are considerably involved in the pathology of atherosclerosis; nevertheless, the fundamental mechanism is still largely unclear. This research sought to examine the function of lipophagy in lipid metabolism disorder-induced atherosclerosis and its fundamental mechanisms. Previously, Sirt6 has been reported to stimulate plaque stability by promoting macrophage autophagy. However, its role in macrophage lipophagy and its relationship with Wnt1 remains to be established. In this study, ApoE−/−: Sirt6−/− and ApoE−/−: Sirt6Tg mice were used and lipid droplets were analysed via transmission electron microscopy and Bodipy 493/503 staining in vitro. Atherosclerotic plaques in ApoE−/−: Sirt6−/− mice showed greater necrotic cores and lower stability score. Reconstitution of Sirt6 in atherosclerotic mice improved lipid metabolism disorder and prevented the progression of atherosclerosis. Furthermore, macrophages with Ac-LDL intervention showed more lipid droplets and increased expression of adipophilin and PLIN2. Reconstitution of Sirt6 recruited using SNF2H suppressed Wnt1 expression and improved lipid metabolism disorder by promoting lipophagy. In addition, downregulation of Sirt6 expression in Ac-LDL-treated macrophages inhibited lipid droplet degradation and stimulated foam cell formation. Innovative discoveries in the research revealed that atherosclerosis is caused by lipid metabolism disorders due to downregulated Sirt6 expression. Thus, modulating Sirt6’s function in lipid metabolism might be a useful therapeutic approach for treating atherosclerosis.
Identification of key lipid metabolism-related genes in Alzheimer’s disease
Authors: Zeng Youjie , Cao Si , Li Nannan , Tang Juan , Lin Guoxin
Published: September 2023

Background

Alzheimer’s disease (AD) represents profound degenerative conditions of the brain that cause significant deterioration in memory and cognitive function. Despite extensive research on the significant contribution of lipid metabolism to AD progression, the precise mechanisms remain incompletely understood. Hence, this study aimed to identify key differentially expressed lipid metabolism-related genes (DELMRGs) in AD progression.

Methods

Comprehensive analyses were performed to determine key DELMRGs in AD compared to controls in GSE122063 dataset from Gene Expression Omnibus. Additionally, the ssGSEA algorithm was utilized for estimating immune cell levels. Subsequently, correlations between key DELMRGs and each immune cell were calculated specifically in AD samples. The key DELMRGs expression levels were validated via two external datasets. Furthermore, gene set enrichment analysis (GSEA) was utilized for deriving associated pathways of key DELMRGs. Additionally, miRNA-TF regulatory networks of the key DELMRGs were constructed using the miRDB, NetworkAnalyst 3.0, and Cytoscape software. Finally, based on key DELMRGs, AD samples were further segmented into two subclusters via consensus clustering, and immune cell patterns and pathway differences between the two subclusters were examined.

Results

Seventy up-regulated and 100 down-regulated DELMRGs were identified. Subsequently, three key DELMRGs (DLD, PLPP2, and PLAAT4) were determined utilizing three algorithms [(i) LASSO, (ii) SVM-RFE, and (iii) random forest]. Specifically, PLPP2 and PLAAT4 were up-regulated, while DLD exhibited downregulation in AD cerebral cortex tissue. This was validated in two separate external datasets (GSE132903 and GSE33000). The AD group exhibited significantly altered immune cell composition compared to controls. In addition, GSEA identified various pathways commonly associated with three key DELMRGs. Moreover, the regulatory network of miRNA-TF for key DELMRGs was established. Finally, significant differences in immune cell levels and several pathways were identified between the two subclusters.

Conclusion

This study identified DLD, PLPP2, and PLAAT4 as key DELMRGs in AD progression, providing novel insights for AD prevention/treatment.
Insight into the underlying molecular mechanism of dilated cardiomyopathy through integrative analysis of data mining, iTRAQ-PRM proteomics and bioinformatics
Authors: Xiong Hongli , Zheng Zhe , Zhao Congcong , Zhao Minzhu , Wang Qi , Zhang Peng , Li Yongguo , Zhu Ying , Zhu Shisheng , Li Jianbo
Published: September 2023

Background

DCM is a common cardiomyopathy worldwide, which is characterized by ventricular dilatation and systolic dysfunction. DCM is one of the most widespread diseases contributing to sudden death and heart failure. However, our understanding of its molecular mechanisms is limited because of its etiology and underlying mechanisms. Hence, this study explored the underlying molecular mechanism of dilated cardiomyopathy through integrative analysis of data mining, iTRAQ-PRM proteomics and bioinformatics

Methods

DCM target genes were downloaded from the public databases. Next, DCM was induced in 20 rats by 8 weeks doxorubicin treatment (2.5 mg/kg/week). We applied isobaric tags for a relative and absolute quantification (iTRAQ) coupled with proteomics approach to identify differentially expressed proteins (DEPs) in myocardial tissue. After association analysis of the DEPs and the key target genes, subsequent analyses, including functional annotation, pathway enrichment, validation, were performed.

Results

Nine hundred thirty-five genes were identified as key target genes from public databases. Meanwhile, a total of 782 DEPs, including 348 up-regulated and 434 down-regulated proteins, were identified in our animal experiment. The functional annotation of these DEPs revealed complicated molecular mechanisms including TCA cycle, Oxidative phosphorylation, Cardiac muscle contraction. Moreover, the DEPs were analyzed for association with the key target genes screened in the public dataset. We further determined the importance of these three pathways.

Conclusion

Our results demonstrate that TCA cycle, Oxidative phosphorylation, Cardiac muscle contraction played important roles in the detailed molecular mechanisms of DCM.
Analysis of differential membrane proteins related to matrix stiffness-mediated metformin resistance in hepatocellular carcinoma cells
Authors: Gao Xiangyu , Qian Jiali , Zhang Yang , Wang Heming , Cui Jiefeng , Yang Yehong
Published: September 2023

Background

Our previous work shows that increased matrix stiffness not only alters malignant characteristics of hepatocellular carcinoma (HCC) cells, but also attenuates metformin efficacy in treating HCC cells. Here, we identified differential membrane proteins related to matrix stiffness-mediated metformin resistance for better understand therapeutic resistance of metformin in HCC.

Methods

Differential membrane proteins in HCC cells grown on different stiffness substrates before and after metformin intervention were screened and identified using isobaric tags for relative and absolute quantification (iTRAQ) labeling coupled with the liquid chromatography-tandem mass spectrometry (LC–MS/MS), then bioinformatic analysis were applied to determine candidate membrane protein and their possible signaling pathway.

Results

A total of 5159 proteins were identified and 354 differential membrane proteins and membrane associated proteins, which might be associated with matrix stiffness-mediated metformin resistance were discovered. Then 94 candidate membrane proteins including 21 up-regulated protein molecules and 73 down-regulated protein molecules were further obtained. Some of them such as Annexin A2 (ANXA2), Filamin-A (FLNA), Moesin (MSN), Myosin-9 (MYH9), Elongation factor 2 (eEF2), and Tax1 binding Protein 3 (TAX1BP3) were selected for further validation. Their expressions were all downregulated in HCC cells grown on different stiffness substrates after metformin intervention. More importantly, the degree of decrease was obviously weakened on the higher stiffness substrate compared with that on the lower stiffness substrate, indicating that these candidate membrane proteins might contribute to matrix stiffness-mediated metformin resistance in HCC.

Conclusions

There was an obvious change in membrane proteins in matrix stiffness-mediated metformin resistance in HCC cells. Six candidate membrane proteins may reflect the response of HCC cells under high stiffness stimulation to metformin intervention, which deserve to be investigated in the future.
Lymph node ratio and hematological parameters predict relapse-free survival in patients with high grade rectal neuroendocrine neoplasms after radical resection: a multicenter prognostic study
Authors: Zeng Xinyu , Zhang Peng , Zhu Guangsheng , Li Chengguo , Zhang Rui , Yu Minhao , Lin Guole , Di Maojun , Jiang Congqing , Li Yong , Sun Yueming , Xia Lijian , Chi Pan , Tao Kaixiong
Published: September 2023

Background

The prognostic nutritional index (PNI), alkaline phosphatase (ALP), and lymph node ratio (LNR) are reportedly related to prognosis. The aim of this study was to elucidate the clinical importance of the LNR and hematological parameters in patients with high grade rectal neuroendocrine neoplasms (HG-RNENs) who were undergoing radical resection.

Methods

We reviewed the medical records of patients with HG-RNENs from 17 large-scale medical centers in China (January 1, 2010–April 30, 2022). A nomogram was constructed by using a proportional hazard model. Bootstrap method was used to draw calibration plots to validate the reproducibility of the model. Concordance index (C-Index), decision curve analysis (DCA), and time-dependent area under the receiver operating characteristic curve (TD-AUC) analysis were used to compare the prognostic predictive power of the new model with American Joint Committee on Cancer (AJCC) TNM staging and European Neuroendocrine Tumor Society (ENETS) TNM staging.

Results

A total of 85 patients with HG-RNENs were enrolled in this study. In the 45 patients with HG-RNENs who underwent radical resection, PNI ≤ 49.13 (HR: 3.997, 95% CI: 1.379–11.581, P = 0.011), ALP > 100.0 U/L (HR: 3.051, 95% CI: 1.011–9.205, P = 0.048), and LNR > 0.40 (HR: 6.639, 95% CI: 2.224–19.817, P = 0.0007) were independent predictors of relapse-free survival. The calibration plots suggested that the nomogram constructed based on the three aforementioned factors had good reproducibility. The novel nomogram revealed a C-index superior to AJCC TNM staging (0.782 vs 0.712) and ENETS TNM staging (0.782 vs 0.657). Also, the new model performed better compared to AJCC TNM staging and ENETS TNM staging in DCA and TD-AUC analyses.

Conclusions

LNR, ALP, and PNI were independent prognostic factors in patients with HG-RNENs after radical resection, and the combined indicator had better predictive efficacy compared with AJCC TNM staging and ENETS TNM staging.
Reciprocal regulation of TWIST1 and OGT determines the decitabine efficacy in MDS/AML
Authors: Li Hongjiao , Wang Yi , Feng Shuang , Chang Kaijing , Yu Xinwen , Yang Fenfang , Huang Haozhe , Wang Yuanbo , Li Xiang , Guan Feng
Published: September 2023

Chemoresistance poses a significant impediment to effective treatment strategies for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Our previous study unveiled that oncogene TWIST1 interacted with DNA methyltransferase 3a (DNMT3a) to regulate the decitabine (DAC) resistance in MDS/AML. However, the underlying mechanism of TWIST1 dysregulation in DAC resistance remained enigmatic. Here, we found that O-GlcNAc modification was upregulated in CD34+ cells from MDS/AML patients who do not respond to DAC treatment. Functional study revealed that O-GlcNAcylation could stabilize TWIST1 by impeding its interaction with ubiquitin E3 ligase CBLC. In addition, as one typical transcription factor, TWIST1 could bind to the promoter of O-GlcNAc transferase (OGT) gene and activate its transcription. Collectively, we highlighted the crucial role of the O-GlcNAcylated TWIST1 in the chemoresistance capacity of MDS/AML clonal cells, which may pave the way for the development of a new therapeutic strategy targeting O-GlcNAcylated proteins and reducing the ratio of MDS/AML relapse.
Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis
Authors: Ren Jun-Song , Bai Wen , Ding Jing-Juan , Ge Hui-Min , Wang Su-Yu , Chen Xi , Jiang Qin
Published: September 2023

Background

Pathological neovascularization plays a pivotal role in the onset and progression of tumors and neovascular eye diseases. Despite notable advancements in the development of anti-angiogenic medications that target vascular endothelial growth factor (VEGF) and its receptors (VEGFRs), the occurrence of adverse reactions and drug resistance has somewhat impeded the widespread application of these drugs. Therefore, additional investigations are warranted to explore alternative therapeutic targets. In recent years, owing to the swift advancement of high-throughput sequencing technology, pan-cancer analysis and single-cell sequencing analysis have emerged as pivotal methodologies and focal areas within the domain of omics research, which is of great significance for us to find potential targets related to the regulation of pathological neovascularization.

Methods

Pan-cancer analysis and scRNA-seq data analysis were employed to forecast the association between Actin filament-associated protein 1 like 1 (AFAP1L1) and the development of tumors and endothelial cells. Tumor xenograft model and ocular pathological neovascularization model were constructed as well as Isolectin B4 (IsoB4) staining and immunofluorescence staining were used to assess the effects of AFAP1L1 on the progression of neoplasms and neovascular eye diseases in vivo. Transwell assay, wound scratch assay, tube forming assay, three-dimensional germination assay, and rhodamine-phalloidin staining were used to evaluate the impact of AFAP1L1 on human umbilical vein endothelial cells (HUVECs) function in vitro; Dual luciferase reporting, qRT-PCR and western blot were used to investigate the upstream and downstream mechanisms of pathological neovascularization mediated by AFAP1L1.

Results

Our investigation revealed that AFAP1L1 plays a crucial role in promoting the development of various tumors and demonstrates a strong correlation with endothelial cells. Targeted suppression of AFAP1L1 specifically in endothelial cells in vivo proves effective in inhibiting tumor formation and ocular pathological neovascularization. Mechanistically, AFAP1L1 functions as a hypoxia-related regulatory protein that can be activated by HIF-1α. In vitro experiments demonstrated that reducing AFAP1L1 levels can reverse hypoxia-induced excessive angiogenic capacity in HUVECs. The principal mechanism of angiogenesis inhibition entails the regulation of tip cell behavior through the YAP-DLL4-NOTCH axis.

Conclusion

In conclusion, AFAP1L1, a newly identified hypoxia-related regulatory protein, can be activated by HIF-1α. Inhibiting AFAP1L1 results in the inhibition of angiogenesis by suppressing the germination of endothelial tip cells through the YAP-DLL4-NOTCH axis. This presents a promising therapeutic target to halt the progression of tumors and neovascular eye disease.
Treatment outcomes of stereotactic body radiation therapy for primary and metastatic sarcoma of the spine
Authors: Kim Eunji , Kim Mi-Sook , Paik Eun Kyung , Chang Ung-Kyu , Kong Chang-Bae
Published: September 2023

Purpose

This study evaluated the treatment outcomes of spine stereotactic body radiation therapy (SBRT) in sarcoma patients.

Materials and methods

A total of 44 sarcoma patients and 75 spinal lesions (6 primary tumors, 69 metastatic tumors) treated with SBRT were retrospectively reviewed between 2006 and 2017. The median radiation dose was 33 Gy (range, 18–45 Gy) in 3 fractions (range, 1–5) prescribed to the 75% isodose line.

Results

The median follow-up duration was 18.2 months. The 1-year local control was 76.4%, and patients treated with single vertebral body were identified as a favorable prognostic factor on multivariate analyses. Progression-free survival at 1 year was 31.9%, with the interval between initial diagnosis and SBRT and extent of disease at the time of treatment being significant prognostic factors. The 1-year overall survival was 80.5%, and PTV and visceral metastases were independently associated with inferior overall survival.

Conclusion

SBRT for spinal sarcoma is effective in achieving local control, particularly when treating a single vertebral level with a limited extent of disease involvement, resulting in an excellent control rate. The extent of disease at the time of SBRT is significantly correlated with survival outcomes and should be considered when treating spine sarcoma.
LncRNA MSTRG.22719.16 mediates the reduction of enoxaparin sodium high-viscosity bone cement-induced thrombosis by targeting the ocu-miR-326-5p/CD40 axis
Authors: Sang Linchao , Ding Luobin , Hao Kangning , Zhang Ce , Shen Xiaoyu , Sun Hui , Fu Dehao , Qi Xiangbei
Published: September 2023

Objective

Polymethylmethacrylate (PMMA) bone cement promotes the development of local thrombi. Our study found that a novel material, ES-PMMA bone cement, can reduce local thrombosis. We used a simple and reproducible animal model to confirm the reduction in local thrombosis and explored the associated molecular mechanism.

Methods

New Zealand rabbits, which were used to model thrombosis using extracorporeal carotid artery shunts, were divided into the following two groups, with 3 rabbits in each group: the PMMA bone cement group and the ES-PMMA bone cement group. Four hours after modelling, experimental samples, including thrombotic and vascular tissues, were collected. Thrombotic samples from the PMMA group and ES-PMMA group were subjected to lncRNA sequencing, and a lncRNA microarray was used to screen the differentially expressed lncRNAs. The expression of thrombomodulin in endothelial cells was quantified in vascular tissue samples. Differences in the lncRNA expression profiles between the thrombotic samples of the PMMA group and ES-PMMA group were assessed by base-to-base alignment in the intergenic regions of genomes. The lncRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) network was established in light of ceRNA theory. Thrombosis was observed in the PMMA group and ES-PMMA group.

Results

The thrombotic weight was 0.00706 ± 0.00136 g/cm in the PMMA group and 0.00551 ± 0.00115 g/cm in the ES-PMMA group. Quantitative real-time polymerase chain reaction (RT–q-CR) and Western blotting revealed that the expression of CD40, which can regulate thrombosis in vascular endothelial cells, was significantly lower in the ES-PMMA group than in the PMMA group. High-throughput sequencing was used to identify 111 lncRNAs with lower expression in the ES-PMMA group than in the PMMA group. Through bioinformatics investigation, lncRNA MSTRG22719.16/ocu-miR-326-5p/CD40 binding sites were selected. Fluorescent in situ RNA hybridization (FISH) was performed to verify the lower expression of lncRNA MSTRG.22719.16 in vascular tissues from the ES-PMMA group. A dual-luciferase reporter gene assay was applied to verify that ocu-miR-326-5p binds the CD40 3ʹ-UTR and targets lncRNA MSTRG.22719.16.

Conclusion

Compared with PMMA bone cement, ES-PMMA bone cement can reduce thrombosis through the lncRNA MSTRG.22719.16/ocu-miR-326-5p/CD40 axis.
Circ_0000396 suppresses the proliferation and inflammation of rheumatoid arthritis synovial fibroblasts by targeting miR-574-5p/RSPO1 axis
Authors: Yu Hongchao , Yang Jin , Chen Kun , Kang Wulin , Zhu Fengfeng
Published: September 2023

Background

Circular RNAs (circRNAs) are important regulators on the onset and progression of rheumatoid arthritis (RA). Our purpose is to explore the role and underpin mechanism of circ_0000396 in RA progression.

Methods

RA patients (n = 39) and healthy volunteers (n = 33) were recruited from the Affiliated Hospital of Shaanxi University of Chinese Medicine for the present work. Circ_0000396, microRNA-574-5p (miR-574-5p) and R-spondin 1 (RSPO1) RNA levels were analyzed by reverse transcription-quantitative polymerase chain reaction. Cell proliferation was analyzed by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, and 5-ethynyl-2′-deoxyuridine (EDU) assay. Cell apoptosis was assessed by flow cytometry. Protein expression levels of proliferating cell nuclear antigen (PCNA), Cyclin D1, Cyclin E1, BCL2-associated × protein (Bax), B-cell lymphoma-2 (Bcl2), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and RSPO1 were detected by western blot assay. Enzyme-linked immunosorbent assay (ELISA) was conducted to analyze the secretion of pro-inflammatory cytokines including IL-1β and TNF-α. The interaction between miR-574-5p and circ_0000396 or RSPO1 was confirmed by dual-luciferase reporter assay and RNA-pull down assay.

Results

Circ_0000396 expression was notably down-regulated in RA patients compared with healthy controls. Circ_0000396 overexpression suppressed the proliferation and inflammatory response and triggered the apoptosis of RA synovial fibroblasts (RASFs), accompanied by decreases in PCNA, Cyclin D1, Cyclin E1, Bcl2, IL-1β and TNF-α protein expression and an increase in Bax protein expression. Circ_0000396 acted as a molecular sponge for miR-574-5p, and circ_0000396 overexpression-mediated protective effects on RASFs dysfunction were largely reversed by the introduction of miR-574-5p mimics. miR-574-5p interacted with the 3’ untranslated region (3’UTR) of RSPO1, and miR-574-5p negatively regulated RSPO1 expression in RASFs. Circ_0000396 could up-regulate the expression of RSPO1 by sponging miR-574-5p in RASFs. RSPO1 interference largely overturned circ_0000396 overexpression-mediated effects in RASFs.

Conclusion

Circ_0000396 restrained the proliferation and inflammation and induced the apoptosis of RASFs by mediating miR-574-5p/RSPO1 axis, which provided novel potential targets for RA treatment.