bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated self-management support provided by primary care nurses to persons with chronic diseases and common mental disorders: a qualitative study
Authors: Beaudin Jérémie , Chouinard Maud-Christine , Hudon Émilie , Hudon Catherine
Published: June 2024

Background

More and more people suffer from concomitant chronic physical diseases and common mental disorders, calling for integrated self-management support in primary care. However, self-management support of chronic physical diseases and common mental disorders is not clearly operationalized by guidelines and is still conducted in silos by primary care nurses, especially in favour of chronic diseases. This study aims to better understand primary care nurses’ experience of integrated self-management support for people with physical chronic diseases and common mental disorders.

Methods

An interpretive descriptive qualitative approach was conducted with 23 primary care nurses from family medicine groups in Quebec (Canada). They were selected through purposive and snowball sampling methods to participate in an individual interview. Data were analysed using an iterative inductive and deductive analysis (Rainbow Model of Integrated Care and the Practical Reviews in Self-Management Support (PRISMS) taxonomy).

Results

Nurses’ experience of integrated self-management support for people with CD and CMD was structured around: (1) elements of the approach; (2) clinical integration through prevention and health promotion; and (3) operationalization of integrated self-management support. Several elements deemed essential to integrated self-management support were identified. Nurses offered integrated self-management support through prevention of risk factors and promotion of a healthy lifestyle for physical chronic diseases and common mental disorders. Nurses’ self-management support activities included education, action plans, monitoring, and many practical, psychological, and social support strategies. A model of integrated self-management support for primary care nursing is proposed to better understand its clinical integration.

Conclusion

This study presents clinical integration of self-management support and activities for people with physical chronic diseases and common mental disorders in primary care settings. Understanding integrated self-management support will help implement future interventions.
Healthcare professionals’ perceptions of the contributions of rehabilitation coordinators to patients in Swedish psychiatric care: a qualitative descriptive study
Authors: Andersén Åsa , Carpentsier Beatrice , Berglund Erik , Carlsson Maria
Published: June 2024

Background

Rehabilitation coordinators have gradually been introduced into Swedish psychiatric care to support individuals on sick leave to return-to-work or enter work.

Aim

To explore healthcare professionals’ perspectives on the contributions a rehabilitation coordinator can make to patients in psychiatric care.

Materials and methods

A descriptive qualitative design was used, and data were collected through interviews. Twelve healthcare professionals in psychiatric care participated in individual semi-structured interviews. Data were analysed using thematic analysis.

Results

An overarching theme evolved: “The rehabilitation coordinator promotes security and reduces stress in the vocational rehabilitation process”, based on two themes: (1) “Adaptations and support based on the patient’s needs” and (2) “Rehabilitation coordinator efforts as relevant for care”. The themes, in turn, consist of six subthemes.

Conclusions

This study showed that healthcare professionals perceived employment as important for patients’ health and well-being. Therefore, the rehabilitation coordination efforts were not only seen as beneficial for addressing patients’ challenges and needs in managing the vocational rehabilitation process but also as an integral part of the patient’s care.
Prevalence and trends of Chlamydia trachomatis infection in female sex workers and men who have sex with men in China: a systematic review and meta-analysis
Authors: Jian Hui , Lu Wen-Jie , Chen Ze-Wei , Liang Shi-Qing , Yue Xiao-Li , Li Jing , Zhang Jia-Hui , Gong Xiang-Dong
Published: June 2024

Introduction

Chlamydia trachomatis infection can cause a significant disease burden in high-risk populations. This study aimed to assess the overall prevalence of C. trachomatis infection, and determine the long-term trends and geographic distribution of this infection among female sex workers (FSWs) and men who have sex with men (MSM) in China.

Methods

The PubMed, Web of Science, CNKI, Wanfang Data and VIP databases were searched from 1 January 1990 through 30 April 2023. Publications in which C. trachomatis infection was detected using nucleic acid amplification tests (NAATs) were included. The Q test and I2 statistics were used to assess the heterogeneity between studies. A random-effect model was used to estimate the pooled prevalence of C. trachomatis infection. Subgroup, meta-regression, and sensitivity analyses were performed to explore the sources of heterogeneity. Publication bias was evaluated using Egger’s test. Trend analysis of the prevalence was performed using the Jonckheere-Terpstra trend test method.

Results

Sixty-one studies were eligible for inclusion (including 38 for FSWs and 23 for MSM). The pooled prevalence of C. trachomatis infection was 19.5% (95% CI: 16.4, 23.0) among FSWs and 12.7% (95% CI: 9.2, 17.7) in the rectum, 6.4% (95% CI: 5.3, 7.8) in the urethra and 1.3% (95% CI: 0.8, 2.1) in the oropharynx from MSM in China. The subgroup analyses showed that the sample size, study period, study region, specimen collection type, molecular diagnosis method, and recruitment site could explain some heterogeneity among studies of FSWs, and the publication language, study period, study region, molecular diagnosis method, and specimen collection anatomical site could explain some heterogeneity among studies of MSM. From 1998 to 2004, 2005 to 2009, 2010 to 2015, and 2016 to 2021, the pooled prevalence of C. trachomatis infection among FSWs were 30.3%, 19.9%, 21.4%, and 11.3%, respectively. For MSM, the pooled prevalence from 2003 to 2009, 2010 to 2015, and 2016 to 2022 were 7.8%, 4.7%, and 6.5%, respectively. However, no overall decline in the prevalence of C. trachomatis infection was observed among FSWs (z = -1.51, P = 0.13) or MSM (z = -0.71, P = 0.48) in China.

Conclusions

The prevalence of C. trachomatis infection was high in these two high-risk populations in China. The findings of this study provide evidence for the formulation of effective surveillance and screening strategies for the prevention and control of C. trachomatis infection among these two specific populations.
Disparities in cause-specific mortality by health insurance type and premium: evidence from Korean NHIS-HEALS cohort study, 2002–2019
Authors: Kim Ye-Seul , Kim Joungyoun , Kim Yonghoon , Kang Hee-Taik
Published: June 2024

Background

Although one’s socioeconomic status affects health outcomes, limited research explored how South Korea’s National Health Insurance (NHI) system affects mortality rates. This study investigated whether health insurance type and insurance premiums are associated with mortality.

Methods

Based on the National Health Insurance Service-Health Screening cohort, 246,172 men and 206,534 women aged ≥ 40 years at baseline (2002–2003) were included and followed until 2019. Health insurance type was categorized as employee-insured (EI) or self-employed-insured (SI). To define low, medium, and high economic status groups, we used insurance premiums at baseline. Death was determined using the date and cause of death included in the cohort. Cox proportional hazard models were used to analyze the association between insurance factors and the overall and cause-specific mortality.

Results

The SI group had a significantly higher risk of overall death compared to the EI group (adjusted hazard ratio (HR) [95% confidence interval]: 1.13 [1.10–1.15] for men and 1.18 [1.15–1.22] for women), after adjusting for various factors. This trend extended to death from the five major causes of death in South Korea (cancer, cardiovascular disease, cerebrovascular disease, pneumonia, and intentional self-harm) and from external causes, with a higher risk of death in the SI group (vs. the EI group). Further analysis stratified by economic status revealed that individuals with lower economic status faced higher risk of overall death and cause-specific mortality in both sexes, compared to those with high economic status for both health insurance types.

Conclusion

This nationwide study found that the SI group and those with lower economic status faced higher risk of overall mortality and death from the five major causes in South Korea. These findings highlight the potential disparities in health outcomes within the NHI system. To address these gaps, strategies should target risk factors for death at the individual level and governments should incorporate such strategies into public health policy development at the population level.

Trial registration

This study was approved by the Institutional Review Board of Chungbuk National University Hospital (CBNUH-202211-HR-0236) and adhered to the principles of the Declaration of Helsinki (1975).
Transcriptome sequencing and bioinformatics analysis of gastrocnemius muscle in type 2 diabetes mellitus rats
Authors: Xu Kuishuai , Zhang Liang , Wang Tianrui , Yu Tengbo , Zhao Xia , Zhang Yingze
Published: June 2024

Objective

Type 2 diabetes mellitus (T2DM) is one of the high risk factors for sarcopenia. However, the pathogenesis of diabetic sarcopenia has not been fully elucidated. This study obtained transcriptome profiles of gastrocnemius muscle in normal and T2DM rats based on high-throughput sequencing technology, which may provide new ideas for exploring the pathogenesis of diabetic sarcopenia.

Methods

Twelve adult male Sprague-Dawley rats were randomly divided into Control group and T2DM group, and gastrocnemius muscle tissue was retained for transcriptome sequencing and real-time quantitative polymerase chain reaction (qRT-PCR) 6 months later. Screening differentially expressed genes (DEGs), Cluster analysis, gene ontology (GO) functional annotation analysis and Kyoto Encyclopedia of Genes and Gnomes (KEGG) functional annotation and enrichment analysis were performed for DEGs. Six DEGs related to apoptosis were selected for qTR-PCR verification.

Results

Transcriptomic analysis showed that there were 1016 DEGs between the gastrocnemius muscle of T2DM and normal rats, among which 665 DEGs were up-regulated and 351 DEGs were down-regulated. GO analysis showed that the extracellular matrix organization was the most enriched in biological processes, with 26 DEGs. The extracellular matrix with 35 DEGs was the most abundant cellular component. The extracellular matrix structural constituent, with 26 DEGs, was the most enriched in molecular functions. The highest number of DEGs enriched in biological processes, cellular components and molecular functions were positive regulation of transcription by RNA polymerase II, nucleus and metal ion binding, respectively. There were 78, 230 and 89 DEGs respectively. KEGG pathway enrichment analysis showed that ECM-receptor interaction, PI3K-Akt signaling pathway and TGF-β signaling pathway(p < 0.001) had higher enrichment degree and number of DEGs. qRT-PCR results showed that the fold change of Map3k14, Atf4, Pik3r1, Il3ra, Gadd45b and Bid were 1.95, 3.25, 2.97, 2.38, 0.43 and 3.6, respectively. The fold change of transcriptome sequencing were 3.45, 2.21, 2.59, 5.39, 0.49 and 2.78, respectively. The transcriptional trends obtained by qRT-PCR were consistent with those obtained by transcriptome sequencing.

Conclusions

Transcriptomic analysis was used to obtain the “gene profiles” of gastrocnemius muscle of T2DM and normal rats. qRT-PCR verification showed that the genes related to apoptosis were differentially expressed. These DEGs and enrichment pathways may provide new ideas for exploring the pathogenesis of diabetic sarcopenia.
Prevalence and associated risk factors for noma in Nigerian children: a systematic review and meta-analysis
Authors: Eleje George Uchenna , Okoh Emeka Emmanuel , Igbodike Emeka Philip , Akinsolu Folahanmi Tomiwa , Nwaokorie Francisca Obiageri , Lusher Joanne Marie , Tantawi Maha El , Salako Abideen Olurotimi , Ezechi Oliver Chukwujekwu , Foláyan Morẹ́nikẹ́ Oluwátóyìn
Published: June 2024

Objectives

To determine the prevalence, case-fatality rate, and associated risk-factors of Noma in children in Nigeria.

Methods

Search was conducted in PubMed, Google Scholar, and Cochrane Library databases. Data were extraction using a double-blind approach. Discrepancies were resolved by a third reviewer. Heterogeneity was evaluated using I2 statistics. Random-effects model was used for the meta-analysis and subgroup analysis was conducted. The study quality was evaluated using standard Critical-Appraisal-Checklist.

Results

Of the 1652 articles identified, 12 studies that met the inclusion criteria included 871 cases of Noma. Two studies had high-risk of bias and were excluded in the meta-analysis. Pooled prevalence of Noma was 2.95% (95%CI:2.19–3.71; Z = 7.60; p < 0.00001, I2:100.0). Case fatality was reported in one study. Sex-distribution had a male-to-female ratio of 1.1:1. Malnutrition (88.42%, 95%CI:52.84–124.00; I2:100.0), measles (40.60%; 95% CI:31.56–49.65; I2:100.0) and malaria (30.75%; 95% CI:30.06–31.45; I2:100.0) were the most notable associated risk-factors. Prevalence of Noma was non-significantly lower in southern (1.96%,95%CI:1.49–2.44;6 studies) than in northern (4.43%; 95%CI:-0.98-9.83; 4 studies) Nigeria. One study reported the prevalence of Noma in children younger than 5 years.

Conclusions

About every 3 in 100 children in Nigeria had Noma and the prevalence was non-significantly higher in northern than southern Nigeria. Malnutrition, measles, and malaria were major associated risk-factors. Case-fatality rate and prevalence based on different age-groups were inconclusive.
A complex metabolic network and its biomarkers regulate laccase production in white-rot fungus Cerrena unicolor 87613
Authors: Zhang Long-Bin , Qiu Xiu-Gen , Qiu Ting-Ting , Cui Zhou , Zheng Yan , Meng Chun
Published: June 2024

Background

White-rot fungi are known to naturally produce high quantities of laccase, which exhibit commendable stability and catalytic efficiency. However, their laccase production does not meet the demands for industrial-scale applications. To address this limitation, it is crucial to optimize the conditions for laccase production. However, the regulatory mechanisms underlying different conditions remain unclear. This knowledge gap hinders the cost-effective application of laccases.

Results

In this study, we utilized transcriptomic and metabolomic data to investigate a promising laccase producer, Cerrena unicolor 87613, cultivated with fructose as the carbon source. Our comprehensive analysis of differentially expressed genes (DEGs) and differentially abundant metabolites (DAMs) aimed to identify changes in cellular processes that could affect laccase production. As a result, we discovered a complex metabolic network primarily involving carbon metabolism and amino acid metabolism, which exhibited contrasting changes between transcription and metabolic patterns. Within this network, we identified five biomarkers, including succinate, serine, methionine, glutamate and reduced glutathione, that played crucial roles in co-determining laccase production levels.

Conclusions

Our study proposed a complex metabolic network and identified key biomarkers that determine the production level of laccase in the commercially promising Cerrena unicolor 87613. These findings not only shed light on the regulatory mechanisms of carbon sources in laccase production, but also provide a theoretical foundation for enhancing laccase production through strategic reprogramming of metabolic pathways, especially related to the citrate cycle and specific amino acid metabolism.
Fish oil supplementation and risk of incident systemic lupus erythematosus: a large population-based prospective study
Authors: Chen Yancong , Li Zhilan , Gao Yinyan , Xu Boya , Zhang Weiru , Wu Irene X.Y.
Published: June 2024

Background

Although fish oil has been considered to have an anti-inflammatory effect and has been proven to play a beneficial role in the incidence of numerous diseases, the association between fish oil supplementation and the risk of systemic lupus erythematosus (SLE) is still unknown. This study aimed at evaluating the correlation between fish oil use and incident SLE in a large population-based prospective cohort.

Methods

390,277 participants without SLE at baseline from the UK Biobank were enrolled. Fish oil use was ascertained through a touchscreen questionnaire at baseline. The incidence of SLE was identified by the International Classification of Diseases version 10 code in medical records or self-report. Cox proportional hazard models were employed to estimate the association between fish oil use and SLE risk.

Results

Fish oil users accounted for 31.47% of participants. During a median follow-up duration of 11.57 years, 141 participants without fish oil use (4.56/100 000 person-years) and 68 participants with fish oil use (4.78/100 000 person-years) developed SLE. In four models with adjustments for different amounts of confounders, there was no significant difference in the risk of SLE between fish oil users and fish oil non-users (all p-values > 0.05). In subgroup analyses, we found that fish oil supplementation was associated with a lower risk of SLE among females with ultraviolet radiation ≥ 3 h/day (hazard ratio: 0.63, 95% confidence interval: 0.40–0.98), which turned insignificant after further adjustment for female-related factors and sun protection measures.

Conclusions

No significant association between fish oil use and overall incident SLE was observed, except in females exposed to prolonged ultraviolet radiation. Subgroup analysis suggested that females exposed to prolonged ultraviolet radiation might benefit from fish oil supplementation in terms of preventing SLE, but it needs to be confirmed in further studies.
Exosomal circSIPA1L3-mediated intercellular communication contributes to glucose metabolic reprogramming and progression of triple negative breast cancer
Authors: Liang Yiran , Ye Fangzhou , Luo Dan , Long Li , Wang Yajie , Jin Yuhan , Wang Lei , Li Yaming , Han Dianwen , Chen Bing , Zhao Wenjing , Wang Lijuan , Yang Qifeng
Published: June 2024

Background

Breast cancer is the most common malignant tumor, and metastasis remains the major cause of poor prognosis. Glucose metabolic reprogramming is one of the prominent hallmarks in cancer, providing nutrients and energy to support dramatically elevated tumor growth and metastasis. Nevertheless, the potential mechanistic links between glycolysis and breast cancer progression have not been thoroughly elucidated.

Methods

RNA-seq analysis was used to identify glucose metabolism-related circRNAs. The expression of circSIPA1L3 in breast cancer tissues and serum was examined by qRT-PCR, and further assessed its diagnostic value. We also evaluated the prognostic potential of circSIPA1L3 by analyzing a cohort of 238 breast cancer patients. Gain- and loss-of-function experiments, transcriptomic analysis, and molecular biology experiments were conducted to explore the biological function and regulatory mechanism of circSIPA1L3.

Results

Using RNA-seq analysis, circSIPA1L3 was identified as the critical mediator responsible for metabolic adaption upon energy stress. Gain- and loss-of-function experiments revealed that circSIPA1L3 exerted a stimulative effect on breast cancer progression and glycolysis, which could also be transported by exosomes and facilitated malignant behaviors among breast cancer cells. Significantly, the elevated lactate secretion caused by circSIPA1L3-mediated glycolysis enhancement promoted the recruitment of tumor associated macrophage and their tumor-promoting roles. Mechanistically, EIF4A3 induced the cyclization and cytoplasmic export of circSIPA1L3, which inhibited ubiquitin-mediated IGF2BP3 degradation through enhancing the UPS7-IGF2BP3 interaction. Furthermore, circSIPA1L3 increased mRNA stability of the lactate export carrier SLC16A1 and the glucose intake enhancer RAB11A through either strengthening their interaction with IGF2BP3 or sponging miR-665, leading to enhanced glycolytic metabolism. Clinically, elevated circSIPA1L3 expression indicated unfavorable prognosis base on the cohort of 238 breast cancer patients. Moreover, circSIPA1L3 was highly expressed in the serum of breast cancer patients and exhibited high diagnostic value for breast cancer patients.

Conclusions

Our study highlights the oncogenic role of circSIPA1L3 through mediating glucose metabolism, which might serve as a promising diagnostic and prognostic biomarker and potential therapeutic target for breast cancer.
Preconceptional paternal caloric restriction of high-fat diet-induced obesity in Wistar rats dysregulates the metabolism of their offspring via AMPK/SIRT1 pathway
Authors: Anuradha Rachakatla , Srinivas M. , Satyavani M. , Suresh K. , Muralidhar MN. , Rajender Rao Kalashikam
Published: June 2024

Background

Obesity is a metabolic syndrome where allelic and environmental variations together determine the susceptibility of an individual to the disease. Caloric restriction (CR) is a nutritional dietary strategy recognized to be beneficial as a weight loss regime in obese individuals. Preconceptional parental CR is proven to have detrimental effects on the health and development of their offspring. As yet studies on maternal CR effect on their offspring are well established but paternal CR studies are not progressing. In current study, the impact of different paternal CR regimes in diet-induced obese male Wistar rats (WNIN), on their offspring concerning metabolic syndrome are addressed.

Methods

High-fat diet-induced obese male Wistar rats were subjected to caloric restriction of 50% (HFCR-I) and 40% (HFCR-II) and then they were mated with normal females. The male parent’s reproductive function was assessed by sperm parameters and their DNMT’s mRNA expression levels were also examined. The offspring’s metabolic function was assessed by physiological, biochemical and molecular parameters.

Results

The HFCR-I male parents have shown reduced body weights, compromised male fertility and reduced DNA methylation activity. Further, the HFCR-I offspring showed attenuation of the AMPK/SIRT1 pathway, which is associated with the progression of proinflammatory status and oxidative stress. In line, the HFCR-I offspring also developed altered glucose and lipid homeostasis by exhibiting impaired glucose tolerance & insulin sensitivity, dyslipidemia and steatosis. However, these effects were largely mitigated in HFCR-II offspring. Regarding the obesogenic effects, female offspring exhibited greater susceptibility than male offspring, suggesting that females are more prone to the influences of the paternal diet.

Conclusion

The findings highlight that HFCR-I resulted in paternal undernutrition, impacting the health of offspring, whereas HFCR-II largely restored the effects of a high-fat diet on their offspring. As a result, moderate caloric restriction has emerged as an effective weight loss strategy with minimal implications on future generations. This underscores the shared responsibility of fathers in contributing to sperm-specific epigenetic imprints that influence the health of adult offspring.
Associations of lipids and lipid-modifying drug target genes with atrial fibrillation risk based on genomic data
Authors: Tao Yuhang , Wang Yuxing , Yin Yongkun , Zhang Kai , Gong Yingchao , Ying Hangying , Jiang Ruhong
Published: June 2024

Background

The causal associations of lipids and the drug target genes with atrial fibrillation (AF) risk remain obscure. We aimed to investigate the causal associations using genetic evidence.

Methods

Mendelian randomization (MR) analyses were conducted using summary-level genome-wide association studies (GWASs) in European and East Asian populations. Lipid profiles (low-density lipoprotein cholesterol, triglyceride, and lipoprotein[a]) and lipid-modifying drug target genes (3-hydroxy-3-methylglutaryl-CoA reductase, proprotein convertase subtilisin/kexin type 9, NPC1-like intracellular cholesterol transporter 1, apolipoprotein C3, angiopoietin-like 3, and lipoprotein[a]) were used as exposures. AF was used as an outcome. The inverse variance weighted method was applied as the primary method. Summary-data-based Mendelian randomization analyses were performed for further validation using expression quantitative trait loci data. Mediation analyses were conducted to explore the indirect effect of coronary heart disease.

Results

In the European population, MR analyses demonstrated that elevated levels of lipoprotein(a) increased AF risk. Moreover, analyses focusing on drug targets revealed that the genetically proxied target gene LPA, which simulates the effects of drug intervention by reducing lipoprotein(a), exhibited an association with AF risk. This association was validated in independent datasets. There were no consistent and significant associations observed for other traits when analyzed in different datasets. This finding was also corroborated by Summary-data-based Mendelian randomization analyses between LPA and AF. Mediation analyses revealed that coronary heart disease plays a mediating role in this association. However, in the East Asian population, no statistically significant evidence was observed to support these associations.

Conclusions

This study provided genetic evidence that Lp(a) may be a causal factor for AF and that LPA may represent a promising pharmacological target for preventing AF in the European population.
Mussel-inspired immunomodulatory and osteoinductive dual-functional hydroxyapatite nanoplatform for promoting bone regeneration
Authors: Qin Danlei , Zhao Yifan , Cheng Rui , Liu Yingyu , Guo Susu , Sun Lingxiang , Guo Yanqin , Hao Fengxiang , Zhao Bin
Published: June 2024

Simultaneously modulating the inflammatory microenvironment and promoting local bone regeneration is one of the main challenges in treating bone defects. In recent years, osteoimmunology has revealed that the immune system plays an essential regulatory role in bone regeneration and that macrophages are critical components. In this work, a mussel-inspired immunomodulatory and osteoinductive dual-functional hydroxyapatite nano platform (Gold/hydroxyapatite nanocomposites functionalized with polydopamine - PDA@Au-HA) is developed to accelerate bone tissues regeneration by regulating the immune microenvironment. PDA coating endows nanomaterials with the ability to scavenge reactive oxygen species (ROS) and anti-inflammatory properties, and it also exhibits an immunomodulatory ability to inhibit M1 macrophage polarization and activate M2 macrophage secretion of osteogenesis-related cytokines. Most importantly, this nano platform promotes the polarization of M2 macrophages and regulates the crosstalk between macrophages and pre-osteoblast cells to achieve bone regeneration. Au-HA can synergistically promote vascularized bone regeneration through sustained release of Ca and P particles and gold nanoparticles (NPs). This nano platform has a synergistic effect of good compatibility, scavenging of ROS, and anti-inflammatory and immunomodulatory capability to accelerate the bone repair process. Thus, our research offers a possible therapeutic approach by exploring PDA@Au-HA nanocomposites as a bifunctional platform for tissue regeneration.
Automatic analysis of nuclear features reveals a non-tumoral predictor of tumor grade in bladder cancer
Authors: Fahoum Ibrahim , Tsuriel Shlomo , Rattner Daniel , Greenberg Ariel , Zubkov Asia , Naamneh Rabab , Greenberg Orli , Zemser-Werner Valentina , Gitstein Gilad , Hagege Rami , Hershkovitz Dov
Published: June 2024

Background & objectives

Tumor grade determines prognosis in urothelial carcinoma. The classification of low and high grade is based on nuclear morphological features that include nuclear size, hyperchromasia and pleomorphism. These features are subjectively assessed by the pathologists and are not numerically measured, which leads to high rates of interobserver variability. The purpose of this study is to assess the value of a computer-based image analysis tool for identifying predictors of tumor grade in bladder cancer.

Methods

Four hundred images of urothelial tumors were graded by five pathologists and two expert genitourinary pathologists using a scale of 1 (lowest grade) to 5 (highest grade). A computer algorithm was used to automatically segment the nuclei and to provide morphometric parameters for each nucleus, which were used to establish the grading algorithm. Grading algorithm was compared to pathologists’ agreement.

Results

Comparison of the grading scores of the five pathologists with the expert genitourinary pathologists score showed agreement rates between 88.5% and 97.5%.The agreement rate between the two expert genitourinary pathologists was 99.5%. The quantified algorithm based conventional parameters that determine the grade (nuclear size, pleomorphism and hyperchromasia) showed > 85% agreement with the expert genitourinary pathologists. Surprisingly, the parameter that was most associated with tumor grade was the 10th percentile of the nuclear area, and high grade was associated with lower 10th percentile nuclei, caused by the presence of more inflammatory cells in the high-grade tumors.

Conclusion

Quantitative nuclear features could be applied to determine urothelial carcinoma grade and explore new biologically explainable parameters with better correlation to grade than those currently used.
125I seed brachytherapy for non-central pelvic recurrence of cervical cancer after external beam radiotherapy
Authors: Di Xuemin , Gao Zhen , Yu Huimin , Liu Xiaoli , Zhao Jinxin , Wang Juan , Zhang Hongtao
Published: June 2024

Objective

To investigate the efficacy of 125I seed brachytherapy for non-central pelvic recurrence of cervical cancer after external beam radiotherapy, and to analyze the clinical influential factors.

Methods

Between June 2015 and April 2022, 32 patients with 41 lesions were treated with 125I seed brachytherapy. The seeds were implanted under the guidance of CT and/or 3D-printed template images at a median dose of 100 Gy (range, 80–120 Gy), and the local control rate (LCR) and survival rates were calculated. We used multivariate logistic regression to identify prognosis predictors, and receiver operating characteristic (ROC) curve analysis to determine the optimal cut-off values.

Results

The median follow-up was 48.52 months (range, 4–86 months), and the 6-, 12-, and 24-month LCR was 88.0%, 63.2%, and 42.1%, respectively. The 1- and 2-year survival rates were 36% and 33%, respectively, and the median survival time was 13.26 months. No significant adverse events occurred. Multivariate regression analysis showed that tumor diameter, tumor stage, and LCR were independent factors influencing survival. ROC curve analysis showed that the area under the curve for tumor diameter and D90 were 0.765 and 0.542, respectively, with cut-off values of 5.3 cm and 108.5 Gy.

Conclusions

The present findings indicate that 125I seed brachytherapy is feasible for treating non-central pelvic recurrence of cervical cancer after external beam radiotherapy. Further, tumor diameter < 5.3 cm and immediate postoperative D90 > 108.5 Gy were associated with better efficacy.
Compliance of volunteers in a fully-enclosed patient rotation system for MR-guided radiation therapy: a prospective study
Authors: Beyer Cedric , Paul Katharina Maria , Dorsch Stefan , Echner Gernot , Dinkel Fabian , Welzel Thomas , Seidensaal Katharina , Hörner-Rieber Juliane , Jäkel Oliver , Debus Jürgen , Klüter Sebastian
Published: June 2024

Background

Particle therapy makes a noteworthy contribution in the treatment of tumor diseases. In order to be able to irradiate from different angles, usually expensive, complex and large gantries are used. Instead rotating the beam via a gantry, the patient itself might be rotated. Here we present tolerance and compliance of volunteers for a fully-enclosed patient rotation system in a clinical magnetic resonance (MR)-scanner for potential use in MR-guided radiotherapy, conducted within a prospective evaluation study.

Methods

A patient rotation system was used to simulate and perform magnetic resonance imaging (MRI)-examinations with 50 volunteers without an oncological question. For 20 participants, the MR-examination within the bore was simulated by introducing realistic MRI noise, whereas 30 participants received an examination with image acquisition. Initially, body parameters and claustrophobia were assessed. The subjects were then rotated to different angles for simulation (0°, 45°, 90°, 180°) and imaging (0°, 70°, 90°, 110°). At each angle, anxiety and motion sickness were assessed using a 6-item State-Trait-Anxiety-Inventory (STAI-6) and a modified Motion Sickness Assessment Questionnaire (MSAQ). In addition, general areas of discomfort were evaluated.

Results

Out of 50 subjects, three (6%) subjects terminated the study prematurely. One subject dropped out during simulation due to nausea while rotating to 45°. During imaging, further two subjects dropped out due to shoulder pain from positioning at 90° and 110°, respectively. The average result for claustrophobia (0 = no claustrophobia to 4 = extreme claustrophobia) was none to light claustrophobia (average score: simulation 0.64 ± 0.33, imaging 0.51 ± 0.39). The mean anxiety scores (0% = no anxiety to 100% = maximal anxiety) were 11.04% (simulation) and 15.82% (imaging). Mean motion sickness scores (0% = no motion sickness to 100% = maximal motion sickness) of 3.5% (simulation) and 6.76% (imaging) were obtained across all participants.

Conclusion

Our study proves the feasibility of horizontal rotation in a fully-enclosed rotation system within an MR-scanner. Anxiety scores were low and motion sickness was only a minor influence. Both anxiety and motion sickness showed no angular dependency. Further optimizations with regard to immobilization in the rotation device may increase subject comfort.
Long non-coding RNA MIAT serves as a biomarker of fragility fracture and promotes fracture healing
Authors: Yu Chao , Chen Binbin , Su Hui , Yang Yiqun
Published: June 2024

Background

Fragility fracture is common in the elderly. Osteoblast differentiation is essential for bone healing and regeneration. Expression pattern of long non-coding RNA MIAT during fracture healing was examined, and its role in osteoblast differentiation was investigated.

Methods

90 women with simple osteoporosis and 90 women with fragility fractures were included. Another 90 age-matched women were set as the control group. mRNA levels were tested using RT-qPCR. Cell viability was detected via CCK-8, and osteoblastic biomarkers, including ALP, OCN, Collagen I, and RUNX2 were tested via ELISA. The downstream miRNAs and genes targeted by MIAT were predicted by bioinformatics analysis, whose functions and pathways were annotated via GO and KEGG analysis.

Results

Serum MIAT was upregulated in osteoporosis women with high accuracy of diagnostic efficacy. Serum MIAT was even elevated in the fragility fracture group, but decreased in a time manner after operation. MIAT knockdown promoted osteogenic proliferation and differentiation of MC3T3-E1, but the influences were reversed by miR-181a-5p inhibitor. A total of 137 overlapping target genes of miR-181a-5p were predicted based on the miRDB, TargetScan and microT datasets, which were mainly enriched for terms related to signaling pathways regulating pluripotency of stem cells, cellular senescence, and osteoclast differentiation.

Conclusions

LncRNA MIAT serves as a promising biomarker for osteoporosis, and promotes osteogenic differentiation via targeting miR-181a-5p.
HOXB2 promotes cisplatin resistance by upregulating lncRNA DANCR in ovarian cancer
Authors: Li Xiao , Zheng Zhen , Zhou Wanzhen , Huang Huixian , Zhou Yang , Xu Qinyang , Zhu Xiaolu , Teng Yincheng
Published: June 2024

Ovarian cancer (OV) is a highly fatal malignant disease that commonly manifests at an advanced stage. Drug resistance, particularly platinum resistance, is a leading cause of treatment failure because first-line systemic chemotherapy primarily relies on platinum-based regimens. By analyzing the gene expression levels in the Cancer Genome Atlas database, Genotype-Tissue Expression database, and Gene Expression Omnibus datasets, we discerned that HOXB2 was highly expressed in OV and was associated with poor prognosis and cisplatin resistance. Immunohistochemistry and loss-of-function experiments on HOXB2 were conducted to explore its role in OV. We observed that suppressing HOXB2 could impair the growth and cisplatin resistance of OV in vivo and in vitro. Mechanical investigation and experimental validation based on RNA-Seq revealed that HOXB2 regulated ATP-binding cassette transporter members and the ERK signaling pathway. We further demonstrated that HOXB2 modulated the expression of long non-coding RNA DANCR, a differentiation antagonizing non-protein coding RNA, and thus influenced its downstream effectors ABCA1, ABCG1, and ERK signaling to boost drug resistance and cancer proliferation. These results verified that high expression of HOXB2 correlated with platinum resistance and poor prognosis of OV. Therefore, targeting HOXB2 may be a promising strategy for OV therapy.
Trastuzumab-functionalized bionic pyrotinib liposomes for targeted therapy of HER2-positive breast cancer
Authors: Du Jiaqun , Liu Xiaobang , Sun Junpeng , Wu Qian , Hu Yu , Shi Huan , Zheng Li , Liu Ying , Wu Chao , Gao Yu
Published: June 2024

In this study, we prepared a bionic nanosystem of trastuzumab-functionalized SK-BR-3 cell membrane hybrid liposome-coated pyrotinib (Ptb-M-Lip-Her) for the treatment of HER2-positive breast cancer. Transmission electron microscopy, dynamic light scattering, polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting were used to verify the successful preparation of Ptb-M-Lip-Her. In vitro drug release experiments proved that Ptb-M-Lip-Her had a sustained release effect. Cell uptake experiments and in vivo imaging experiments proved that Ptb-M-Lip-Her had good targeting ability to homologous tumor cells (SK-BR-3). The results of cell experiments such as MTT, flow cytometry, immunofluorescence staining and in vivo antitumor experiments showed that Ptb-M-Lip-Her could significantly promote apoptosis and inhibit the proliferation of SK-BR-3 cells. These results clearly indicated that Ptb-M-Lip-Her may be a promising biomimetic nanosystem for targeted therapy of HER2-positive breast cancer.
A review of applications and limitations of using aquatic macroinvertebrate predators for biocontrol of the African malaria mosquito, Anopheles gambiae sensu lato
Authors: Onen Hudson , Kaddumukasa Martha A. , Kayondo Jonathan K. , Akol Anne M. , Tripet Frédéric
Published: June 2024

Macroinvertebrate predators such as backswimmers (Heteroptera: Notonectidae), dragonflies (Odonata: Aeshnidae), and predatory diving beetles (Coleoptera: Dytiscidae) naturally inhabit aquatic ecosystems. Some aquatic ecosystems inhabited by these macroinvertebrate predator taxa equally form malaria vector larval habitats. The presence of these predators in malaria vector larval habitats can negatively impact on development, adult body size, fecundity, and longevity of the malaria vectors, which form important determinants of their fitness and future vectorial capacity. These potential negative impacts caused by aquatic macroinvertebrate predators on malaria vectors warrant their consideration as biocontrol agents in an integrated program to combat malaria. However, the use of these macroinvertebrate predators in malaria biocontrol is currently constrained by technical bottlenecks linked to their generalist predatory tendencies and often long life cycles, demanding complex rearing systems. We reviewed the literature on the use of aquatic macroinvertebrate predators for biocontrol of malaria vectors from the An. gambiae s.l. complex. The available information from laboratory and semi-field studies has shown that aquatic macroinvertebrates have the potential to consume large numbers of mosquito larvae and could thus offer an additional approaches in integrated malaria vector management strategies. The growing number of semi-field structures available in East and West Africa provides an opportunity to conduct ecological experimental studies to reconsider the potential of using aquatic macroinvertebrate predators as a biocontrol tool. To achieve a more sustainable approach to controlling malaria vector populations, additional, non-chemical interventions could provide a more sustainable approach, in comparison with the failing chemical control tools, and should be urgently considered for integration with the current mosquito vector control campaigns.

Graphical Abstract
Basing intubation of acutely hypoxemic patients on physiologic principles
Authors: Laghi Franco , Shaikh Hameeda , Caccani Nicola
Published: June 2024

The decision to intubate a patient with acute hypoxemic respiratory failure who is not in apparent respiratory distress is one of the most difficult clinical decisions faced by intensivists. A conservative approach exposes patients to the dangers of hypoxemia, while a liberal approach exposes them to the dangers of inserting an endotracheal tube and invasive mechanical ventilation. To assist intensivists in this decision, investigators have used various thresholds of peripheral or arterial oxygen saturation, partial pressure of oxygen, partial pressure of oxygen-to-fraction of inspired oxygen ratio, and arterial oxygen content. In this review we will discuss how each of these oxygenation indices provides inaccurate information about the volume of oxygen transported in the arterial blood (convective oxygen delivery) or the pressure gradient driving oxygen from the capillaries to the cells (diffusive oxygen delivery). The decision to intubate hypoxemic patients is further complicated by our nescience of the critical point below which global and cerebral oxygen supply become delivery-dependent in the individual patient. Accordingly, intubation requires a nuanced understanding of oxygenation indexes. In this review, we will also discuss our approach to intubation based on clinical observations and physiologic principles. Specifically, we consider intubation when hypoxemic patients, who are neither in apparent respiratory distress nor in shock, become cognitively impaired suggesting emergent cerebral hypoxia. When deciding to intubate, we also consider additional factors including estimates of cardiac function, peripheral perfusion, arterial oxygen content and its determinants. It is not possible, however, to pick an oxygenation breakpoint below which the benefits of mechanical ventilation decidedly outweigh its hazards. It is futile to imagine that decision making about instituting mechanical ventilation in an individual patient can be condensed into an algorithm with absolute numbers at each nodal point. In sum, an algorithm cannot replace the presence of a physician well skilled in the art of clinical evaluation who has a deep understanding of pathophysiologic principles.
Diagnostic and prognostic relevance of plain radiographs for periprosthetic joint infections of the hip: a literature review
Authors: Hofmann Ulf Krister , Eleftherakis Georgios , Migliorini Filippo , Fink Bernd , Mederake Moritz
Published: June 2024

Conventional radiography is regularly used to evaluate complications after total hip arthroplasty. In various recent consensus meetings, however, plain radiographs of a potentially infected hip joint have been judged as being only relevant to exclude diagnoses other than infection. Solid data on radiographic presentations of periprosthetic joint infection (PJI) are scarce. As a result, the prognostic value of radiological features in low-grade PJI remains uncertain. The present review article aims to present an overview of the available literature and to develop ideas on future perspectives to define the diagnostic possibilities of radiography in PJIs of the hip. The primary outcome of interest of this systematic review was the radiologic presentation of periprosthetic joint infections of the hip. As secondary outcome of interest served the sensitivity and specificity of the radiologic presentation of periprosthetic joint infections. Of the included articles, 26 were reviews, essays, or case reports and only 18 were clinical studies. Typical radiologic abnormalities of PJI were a periosteal reaction, a wide band of radiolucency at the cement–bone or metal–bone interface, patchy osteolysis, implant loosening, bone resorption around the implant, and transcortical sinus tracts. The frequency of their occurrence is still inadequately defined. A deeper understanding of the underlying causes and the relation between microorganisms to radiologic abnormalities can probably help clinicians in the future to diagnose a PJI. This is why further research shall focus on the radiographic features of PJI.
Alzheimer’s disease and drug delivery across the blood–brain barrier: approaches and challenges
Authors: Iqbal Iram , Saqib Fatima , Mubarak Zobia , Latif Muhammad Farhaj , Wahid Muqeet , Nasir Bushra , Shahzad Hamna , Sharifi-Rad Javad , Mubarak Mohammad S.
Published: June 2024

Alzheimer's disease (AD) is a diverse disease with a complex pathophysiology. The presence of extracellular β-amyloid deposition as neuritic plaques and intracellular accumulation of hyper-phosphorylated tau as neurofibrillary tangles remain the core neuropathologic criteria for diagnosing Alzheimer's disease. Nonetheless, several recent basic discoveries have revealed significant pathogenic roles for other essential cellular and molecular processes. Previously, there were not so many disease-modifying medications (DMT) available as drug distribution through the blood–brain barrier (BBB) is difficult due to its nature, especially drugs of polypeptides nature and proteins. Recently FDA has approved lecanemab as DMT for its proven efficacy. It is also complicated to deliver drugs for diseases like epilepsy or any brain tumor due to the limitations of the BBB. After the advancements in the drug delivery system, different techniques are used to transport the medication across the BBB. Other methods are used, like enhancement of brain blood vessel fluidity by liposomes, infusion of hyperosmotic solutions, and local intracerebral implants, but these are invasive approaches. Non-invasive approaches include the formulation of nanoparticles and their coating with polymers. This review article emphasizes all the above-mentioned techniques, procedures, and challenges to transporting medicines across the BBB. It summarizes the most recent literature dealing with drug delivery across the BBB.