bluuebunny/crossref_metadata_2025 huggingface dataset:
Insomnia in chronic obstructive pulmonary disease and associations with healthcare utilization and costs
Authors: Luyster Faith S. , Boudreaux-Kelly Monique Y. , Bon Jessica M.
Published: March 2023

Insomnia has been linked to adverse chronic obstructive pulmonary disease (COPD) outcomes including exacerbations, yet its impact on COPD-related healthcare utilization and costs is unknown. In this study, we investigated the associations between insomnia and healthcare utilization and costs in patients with COPD. A retrospective cohort of veterans with COPD were identified from national Veterans Affairs administration data for fiscal years 2012–2017. Insomnia was operationalized as having an insomnia diagnosis based on International Classification of Disease codes or having a prescription of > 30 doses of a sedative-hypnotic medication in a given fiscal year. The index date for insomnia was the first date when dual criteria for COPD and insomnia was met. The index date for those without insomnia was set as the COPD index date. Our primary outcomes were 1-year healthcare utilization and costs related to outpatient visits and hospitalizations after index date. COPD-related healthcare utilization variables included number of prescription fills of corticosteroids and/or antibiotics and outpatient visits and hospitalizations with a primary diagnosis of COPD. Out of 1,011,646 patients (96% men, mean age 68.4 years) diagnosed with COPD, 407,363 (38.8%) had insomnia. After adjustment for confounders, insomnia was associated with higher rates of outpatient visits, hospitalizations, and fills for corticosteroids and/or antibiotics, longer hospital length of stay, and $10,344 higher hospitalization costs in the 12 months after index date. These findings highlight the importance of insomnia as a potentially modifiable target for reducing the burden of COPD on patients and healthcare systems.
Elevated urine albumin-to-creatinine ratio increases the risk of new-onset heart failure in patients with type 2 diabetes
Authors: Tao Jie , Sang Dasen , Zhen Libo , Zhang Xinxin , Li Yuejun , Wang Guodong , Chen Shuohua , Wu Shouling , Zhang Wenjuan
Published: March 2023

Background

Although albuminuria has been linked to heart failure in the general population, the relationship between urine albumin-to-creatinine ratio (uACR) and heart failure in type 2 diabetes patients is not well understood. We aimed to investigate the relationship between uACR and new-onset heart failure (HF) in type 2 diabetics.

Methods

We included 9287 Chinese participants with type 2 diabetes (T2D) but no heart failure (HF) who were assessed with uACR between 2014 and 2016. The participants were divided into three groups based on their baseline uACR: normal (< 3 mg/mmol), microalbuminuria (3–30 mg/mmol), and macroalbuminuria (≥ 30 mg/mmol). The relationship between uACR and new-onset HF was studied using Cox proportional hazard models and restricted cubic spline. The area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to see if incorporating uACR into existing models could improve performance.

Results

216 new-onset HF cases (2.33%) were recorded after a median follow-up of 4.05 years. When compared to normal uACR, elevated uACR was associated with a progressively increased risk of new-onset HF, ranging from microalbuminuria (adjusted HR, 2.21; 95% CI 1.59–3.06) to macroalbuminuria (adjusted HR, 6.02; 95% CI 4.11–8.80), and 1 standard deviation (SD) in ln (uACR) (adjusted HR, 1.89; 95% CI 1.68–2.13). The results were consistent across sex, estimated glomerular filtration rate, systolic blood pressure, and glycosylated hemoglobin subgroups. The addition of uACR to established HF risk models improved the HF risk prediction efficacy.

Conclusions

Increasing uACR, even below the normal range, is an independent risk factor for new-onset HF in a type 2 diabetic population. Furthermore, uACR may improve HF risk prediction in community-based T2D patients.
A novel feedback regulated loop of circRRM2-IGF2BP1-MYC promotes breast cancer metastasis
Authors: Hao Ran , Zhang Lei , Si Yangming , Zhang Peng , Wang Yipeng , Li Bangchao , Hu Jie , Qi Yixin
Published: March 2023

Background

Metastasis is the leading cause of mortality in patients with breast cancer (BC). Studies demonstrate that circular RNAs (circRNAs) were involved in BC progression, while the molecular mechanisms remain largely unclear.

Methods

The microArray circRNA profiles were used to explore the differential expression circRNAs in BC and paracancerous normal tissues, and the quantitative reverse transcription-polymerase chain reaction was used to validate their expression level in clinical samples and cell lines. Nuclear/cytosolic fractionation and fluorescence in situ hybridization (FISH) assays were performed to examine circRRM2 (hsa_circ_0052582) subcellular location. The scratch wound healing and transwell assays were conducted to evaluate the impact of circRRM2 on BC cell migration and invasion. We predicted miRNAs that might bind with cricRRM2 and the downstream target genes using bioinformatics analysis and explored their expression levels and prognostic value in BC. FISH, RNA immunoprecipitation, Co-immunoprecipitation, Western blot, and rescue experiments were implemented to figure out circRRM2 function and underlying mechanisms in BC.

Results

The present study revealed several aberrant circRNAs in BC tissues and observed that circRRM2 was upregulated in tumor tissues of 40 patients with BC. High circRRM2 was significantly associated with advanced N stage in patients with BC. Gain- and loss- of function experiments revealed that circRRM2 promoted the migration and invasion of cells and functioned as an oncogene in BC. Mechanism studies showed that circRRM2 competed with miR-31-5p/miR-27b-3p to upregulate the IGF2BP1 expression. Furthermore, IGF2BP1 upregulated the circRRM2 level via interacting with MYC, which functioned as the transcriptional factor of circRRM2. Thus, the positive feedback loop that was composed of circRRM2/IGF2BP1/MYC was identified.

Conclusion

This study confirms that upregulated circRRM2 functions an oncogenic role in BC metastasis. The positive feedback loop of circRRM2/IGF2BP1/MYC enforces the circRRM2 expression, which might offer a potential target for BC treatment.
The function and mechanisms of action of circular RNAs in Urologic Cancer
Authors: Zhang Zi-hao , Wang Yue , Zhang Ya , Zheng Sheng-Feng , Feng Tao , Tian Xi , Abudurexiti Mierxiati , Wang Zhen-Da , Zhu Wen-Kai , Su Jia-Qi , Zhang Hai-Liang , Shi Guo-Hai , Wang Zi-Liang , Cao Da-Long , Ye Ding-Wei
Published: March 2023

Kidney, bladder, and prostate cancer are the three major tumor types of the urologic system that seriously threaten human health. Circular RNAs (CircRNAs), special non-coding RNAs with a stabile structure and a unique back-splicing loop-forming ability, have received recent scientific attention. CircRNAs are widely distributed within the body, with important biologic functions such as sponges for microRNAs, as RNA binding proteins, and as templates for regulation of transcription and protein translation. The abnormal expression of circRNAs in vivo is significantly associated with the development of urologic tumors. CircRNAs have now emerged as potential biomarkers for the diagnosis and prognosis of urologic tumors, as well as targets for the development of new therapies. Although we have gained a better understanding of circRNA, there are still many questions to be answered. In this review, we summarize the properties of circRNAs and detail their function, focusing on the effects of circRNA on proliferation, metastasis, apoptosis, metabolism, and drug resistance in kidney, bladder, and prostate cancers.
Functionalization of curcumin nanomedicines: a recent promising adaptation to maximize pharmacokinetic profile, specific cell internalization and anticancer efficacy against breast cancer
Authors: Zhang Jinku , Sun Jirui , Li Chong , Qiao Haizhi , Hussain Zahid
Published: March 2023

Owing to its diverse heterogeneity, aggressive nature, enormous metastatic potential, and high remission rate, the breast cancer (BC) is among the most prevalent types of cancer associated with high mortality. Curcumin (Cur) is a potent phytoconstituent that has gained remarkable recognition due to exceptional biomedical viability against a wide range of ailments including the BC. Despite exhibiting a strong anticancer potential, the clinical translation of Cur is restricted due to intrinsic physicochemical properties such as low aqueous solubility, chemical instability, low bioavailability, and short plasma half-life. To overcome these shortcomings, nanotechnology-aided developments have been extensively deployed. The implication of nanotechnology has pointedly improved the physicochemical properties, pharmacokinetic profile, cell internalization, and anticancer efficacy of Cur; however, majority of Cur-nanomedicines are still facing grandeur challenges. The advent of various functionalization strategies such as PEGylation, surface decoration with different moieties, stimuli-responsiveness (i.e., pH, light, temperature, heat, etc.), tethering of specific targeting ligand(s) based on the biochemical targets (e.g., folic acid receptors, transferrin receptors, CD44, etc.), and multifunctionalization (multiple functionalities) has revolutionized the fate of Cur-nanomedicines. This study ponders the biomedical significance of various Cur-nanomedicines and adaptable functionalizations for amplifying the physicochemical properties, cytotoxicity via induction of apoptosis, cell internalization, bioavailability, passive and active targeting to the tumor microenvironment (TME), and anticancer efficacy of the Cur while reversing the multidrug resistance (MDR) and reoccurrence in BC. Nevertheless, the therapeutic outcomes of Cur-nanomedicines against the BC have been remarkably improved after adaptation of various functionalizations; however, this evolving strategy still demands extensive research for scalable clinical translation.

Graphical Abstract
Combining nanotechnology with monoclonal antibody drugs for rheumatoid arthritis treatments
Authors: Chi Xiao-Kai , Xu Xiao-Ling , Chen Bang-Yao , Su Jin , Du Yong-Zhong
Published: March 2023

Rheumatoid arthritis (RA) is a systemic immune disease characterized by synovial inflammation. Patients with RA commonly experience significant damage to their hand and foot joints, which can lead to joint deformities and even disability. Traditional treatments have several clinical drawbacks, including unclear pharmacological mechanisms and serious side effects. However, the emergence of antibody drugs offers a promising approach to overcome these limitations by specifically targeting interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and other cytokines that are closely related to the onset of RA. This approach reduces the incidence of adverse effects and contributes to significant therapeutic outcomes. Furthermore, combining these antibody drugs with drug delivery nanosystems (DDSs) can improve their tissue accumulation and bioavailability.Herein, we provide a summary of the pathogenesis of RA, the available antibody drugs and DDSs that improve the efficacy of these drugs. However, several challenges need to be addressed in their clinical applications, including patient compliance, stability, immunogenicity, immunosupression, target and synergistic effects. We propose strategies to overcome these limitations. In summary, we are optimistic about the prospects of treating RA with antibody drugs, given their specific targeting mechanisms and the potential benefits of combining them with DDSs.
Bioengineering of air-filled protein nanoparticles by genetic and chemical functionalization
Authors: Karan Ram , Renn Dominik , Nozue Shuho , Zhao Lingyun , Habuchi Satoshi , Allers Thorsten , Rueping Magnus
Published: March 2023

Background

Various bacteria and archaea, including halophilic archaeon Halobacterium sp. NRC-1 produce gas vesicle nanoparticles (GVNPs), a unique class of stable, air-filled intracellular proteinaceous nanostructures. GVNPs are an attractive tool for biotechnological applications due to their readily production, purification, and unique physical properties. GVNPs are spindle- or cylinder-shaped, typically with a length of 100 nm to 1.5 μm and a width of 30–250 nm. Multiple monomeric subunits of GvpA and GvpC proteins form the GVNP shell, and several additional proteins are required as minor structural or assembly proteins. The haloarchaeal genetic system has been successfully used to produce and bioengineer GVNPs by fusing several foreign proteins with GvpC and has shown various applications, such as biocatalysis, diagnostics, bioimaging, drug delivery, and vaccine development.

Results

We demonstrated that native GvpC can be removed in a low salt buffer during the GVNP purification, leaving the GvpA-based GVNP's shell intact and stable under physiological conditions. Here, we report a genetic engineering and chemical modification approach for functionalizing the major GVNP protein, GvpA. This novel approach is based on combinatorial cysteine mutagenesis within GvpA and genetic expansion of the N-terminal and C-terminal regions. Consequently, we generated GvpA single, double, and triple cysteine variant libraries and investigated the impact of mutations on the structure and physical shape of the GVNPs formed. We used a thiol–maleimide chemistry strategy to introduce the biotechnological relevant activity by maleimide-activated streptavidin–biotin and maleimide-activated SpyTag003-SpyCatcher003 mediated functionalization of GVNPs.

Conclusion

The merger of these genetic and chemical functionalization approaches significantly extends these novel protein nanomaterials' bioengineering and functionalization potential to assemble catalytically active proteins, biomaterials, and vaccines onto one nanoparticle in a modular fashion.

Graphical Abstract
Point-of-care community drug checking technologies: an insider look at the scientific principles and practical considerations
Authors: Gozdzialski Lea , Wallace Bruce , Hore Dennis
Published: March 2023

Drug checking is increasingly being explored outside of festivals and events to be an ongoing service within communities, frequently integrated within responses to illicit drug overdose. The choice of instrumentation is a common question, and the demands on these chemical analytical instruments can be challenging as illicit substances may be more complex and include highly potent ingredients at trace levels. The answer remains nuanced as the instruments themselves are not directly comparable nor are the local demands on the service, meaning implementation factors heavily influence the assessment and effectiveness of instruments. In this perspective, we provide a technical but accessible introduction to the background of a few common drug checking methods aimed at current and potential drug checking service providers. We discuss the following tools that have been used as part of the Vancouver Island Drug Checking Project in Victoria, Canada: immunoassay test strips, attenuated total reflection IR-absorption spectroscopy, Raman spectroscopy from powder samples, surface-enhanced Raman scattering in a solution of colloidal gold nanoparticles, and gas chromatography–mass spectrometry. Using four different drug mixtures received and tested at the service, we illustrate the strengths, limitations, and capabilities of such instruments, and expose the scientific theory to give further insight into their analytical results. Each case study provides a walk-through-style analysis for a practical comparison between data from several different instruments acquired on the same sample. Ideally, a single instrument would be able to achieve all of the objectives of drug checking. However, there is no clear instrument that ticks every box; low cost, portable, rapid, easy-to-use and provides highly sensitive identification and accurate quantification. Multi-instrument approaches to drug checking may be required to effectively respond to increasingly complex and highly potent substances demanding trace level detection and the potential for quantification.
A mixed-methods analysis of risk-reduction strategies adopted by syringe services program participants and non-syringe services program participants in New York City
Authors: Beharie Nisha , Urmanche Adelya , Harocopos Alex
Published: March 2023

Background

Since the emergence of fentanyl in the drug market, syringe services programs (SSPs) have been at the forefront of providing life-saving tools such as naloxone and fentanyl test strips to people who use drugs (PWUD). It is still unclear, however, how the adoption of risk-reduction practices has differed among PWUD in the context of increasing presence of non-pharmaceutical fentanyl in the drug supply. This study aims to assess the adoption of risk-reduction tools (e.g., naloxone) among those engaged with SSP services and those not engaged with SSP services.

Methods

We conducted a mixed-methods study following a convergent parallel design integrating both quantitative and qualitative data. Interviews were conducted with 80 people who used street opioids (i.e., heroin or opioid pills not prescribed), 32 of whom were not engaged in SSP services. Quantitative differences between those engaged and those not engaged in SSPs were assessed using independent samples t tests and Fisher’s exact tests. A thematic analytic approach was employed to compare qualitative responses between the two groups.

Results

Three main themes emerged in our analysis: (1) Both groups expressed an interest in fentanyl test strips (FTS), but those engaged in SSP services found them to be more accessible; (2) there was greater adoption of and enthusiasm for naloxone among SSP participants; and (3) SSP participants were more likely to have or be interested in having someone check in on them when using alone, but stigma and perceived personal risk of overdose prevented widespread adoption of this practice among all participants.

Conclusion

SSPs provide a vital function by facilitating naloxone and FTS distribution to participants who often have little control over their exposure to fentanyl. However, stigma and misconceptions regarding drug use are barriers to people adopting risk-reduction practices, particularly among those not engaged with SSPs.
Clinical phenotypes and prognosis of cytomegalovirus infection in the pediatric systemic lupus erythematosus: a longitudinal analysis
Authors: Zhang Tianyu , Yu Zhongxun , Gao Sihao , Zhang Yuelun , Wang Changyan , Jian Shan , Wang Lin , Gou Lijuan , Li Ji , Ma Mingsheng , Song Hongmei
Published: March 2023

Background

Cytomegalovirus (CMV) plays an important role in the pathogenesis of systemic lupus erythematosus (SLE). However, it is not clear whether the anti-CMV treatment has an impact on the prognosis of SLE patients with CMV infection. We aimed to analyze the clinical characteristics and prognosis of CMV infection in pediatric SLE (pSLE) and to evaluate the effect of anti-CMV treatment on pSLE outcome.

Methods

A retrospective study including 146 pSLE from 2012 to 2021 was conducted. CMV-positive and CMV-negative groups were compared by univariate analysis and stepwise logistic multiple regression to analyze the clinical characteristics of CMV infection in pSLE. Generalized estimating equations (GEE) were used to model the longitudinal dynamics of pSLE disease activity with or without CMV infection and anti-CMV treatment.

Results

The CMV infection rate was 74.7% (109/146) in this pSLE cohort. CMV-positive pSLE patients were more likely to present positive anti-dsDNA antibody, hypocomplementemia, high SLEDAI-2K score and musculoskeletal involvement (P < 0.05). Survival analysis showed that CMV-positive pSLE patients were more prone to disease flare and poorer outcomes. GEE modeling indicated that CMV phosphoprotein 65 (pp65) titers were positively correlated with SLEDAI-2K, and anti-CMV treatment could better reduce pSLE activity than non-treatment (P < 0.05).

Conclusions

CMV infection is highly prevalent among pSLE patients. Positive anti-dsDNA antibody, hypocomplementemia, high SLEDAI-2K score and musculoskeletal involvement were significant clinical clues indicating CMV infections in pSLE. CMV infection is correlated with higher disease activity and poorer outcome. Anti-CMV treatment can reduce disease activity and flares.
Effect of the COVID-19 pandemic on maternal and neonatal health services in three referral hospitals in Guinea: an interrupted time-series analysis
Authors: Millimouno Tamba Mina , Dioubaté Nafissatou , Niane Harissatou , Diallo Mamadou Cellou , Maomou Cécé , Sy Telly , Diallo Ibrahima Sory , Semaan Aline , Delvaux Thérèse , Beňová Lenka , Delamou Alexandre
Published: March 2023

Introduction

In sub-Saharan Africa, there is limited evidence on the COVID-19 health-related effect from front-line health provision settings. Therefore, this study aimed to analyse the effect of the COVID-19 pandemic on routine maternal and neonatal health services in three referral hospitals.

Materials and methods

We conducted an observational study using aggregate monthly maternal and neonatal health services routine data for two years (March 2019–February 2021) in three referral hospitals including two maternities: Hôpital National Ignace Deen (HNID) in Conakry and Hôpital Regional de Mamou (HRM) in Mamou and one neonatology ward: Institut de Nutrition et de Santé de l’Enfant (INSE) in Conakry. We compared indicators of health service utilisation, provision and health outcomes before and during the COVID-19 pandemic periods. An interrupted time-series analysis (ITSA) was performed to assess the relationship between changes in maternal and neonatal health indicators and COVID-19 through cross-correlation.

Results

During COVID-19, the mean monthly number (MMN) of deliveries decreased significantly in HNID (p = 0.039) and slightly increased in HRM. In the two maternities, the change in the MMN of deliveries were significantly associated with COVID-19. The ITSA confirmed the association between the increase in the MMN of deliveries and COVID-19 in HRM (bootstrapped F-value = 1.46, 95%CI [0.036–8.047],p < 0.01). We observed an increasing trend in obstetric complications in HNID, while the trend declined in HRM. The MMN of maternal deaths increased significantly (p = 0.011) in HNID, while it slightly increased in HRM. In INSE, the MMN of neonatal admissions significantly declined (p < 0.001) and this decline was associated with COVID-19. The MMN of neonatal deaths significantly decreased (p = 0.009) in INSE and this decrease was related to COVID-19.

Conclusion

The pandemic negatively affected the maternal and neonatal care provision, health service utilisation and health outcomes in two referral hospitals located in Conakry, the COVID-19 most-affected region.
Inducible nitric oxide synthase deficiency promotes murine-β-coronavirus induced demyelination
Authors: Kamble Mithila , Saadi Fareeha , Kumar Saurav , Saha Bhaskar , Das Sarma Jayasri
Published: March 2023

Background

Multiple sclerosis (MS) is characterized by neuroinflammation and demyelination orchestrated by activated neuroglial cells, CNS infiltrating leukocytes, and their reciprocal interactions through inflammatory signals. An inflammatory stimulus triggers inducible nitric oxide synthase (NOS2), a pro-inflammatory marker of microglia/macrophages (MG/Mφ) to catalyze sustained nitric oxide production. NOS2 during neuroinflammation, has been associated with MS disease pathology; however, studies dissecting its role in demyelination are limited. We studied the role of NOS2 in a recombinant β-coronavirus-MHV-RSA59 induced neuroinflammation, an experimental animal model mimicking the pathological hallmarks of MS: neuroinflammatory demyelination and axonal degeneration.

Objective

Understanding the role of NOS2 in murine-β-coronavirus-MHV-RSA59 demyelination.

Methods

Brain and spinal cords from mock and RSA59 infected 4–5-week-old MHV-free C57BL/6 mice (WT) and NOS2-/- mice were harvested at different disease phases post infection (p.i.) (day 5/6-acute, day 9/10-acute-adaptive and day 30-chronic phase) and compared for pathological outcomes.

Results

NOS2 was upregulated at the acute phase of RSA59-induced disease in WT mice and its deficiency resulted in severe disease and reduced survival at the acute-adaptive transition phase. Low survival in NOS2-/- mice was attributed to (i) high neuroinflammation resulting from increased accumulation of macrophages and neutrophils and (ii) Iba1 + phagocytic MG/Mφ mediated-early demyelination as observed at this phase. The phagocytic phenotype of CNS MG/Mφ was confirmed by significantly higher mRNA transcripts of phagocyte markers-CD206, TREM2, and Arg1 and double immunolabelling of Iba1 with MBP and PLP. Further, NOS2 deficiency led to exacerbated demyelination at the chronic phase as well.

Conclusion

Taken together the results imply that the immune system failed to control the disease progression in the absence of NOS2. Thus, our observations highlight a protective role of NOS2 in murine-β-coronavirus induced demyelination.
A survey on the potential contribution of Reunion Island dye plant species diversity to the market demand for bioactive plant-based dyes and pigments
Authors: Andriamanantena Mahery , Pithon Shamsia , Dijoux Manon , Hoareau Marine , Fontaine Christian , Ferrard Johnny , Lavergne Christophe , Petit Thomas , Caro Yanis
Published: March 2023

Background

Proven toxicity and environmental burdens caused by artificial dyes have motivated dyeing industries to turn to natural alternatives. Plant-based dyestuffs are an interesting group of alternative crops. Reunion Island located in the Indian Ocean is the only European region in the southern hemisphere. It has a great number of assets to find new molecules in the abundant plant biodiversity. However, the dye-producing plants diversity in this island had not been documented to date.

Methodology

The assessment of the Reunion Island’s plant biodiversity through the “PLANTIN” project allowed us to establish here the first ethnobotanical inventory of plants growing on Reunion Island which may have promising properties as a new alternative source of dyes or colorants for the industries. First, an ethnobotanical survey focused on the uses of plants traditionally used in dyeing was conducted on local stakeholders. Then, the importance of different criteria (e.g., endemicity, accessibility and cultivability, plant organs used for the extraction, industrial interests of the species, etc.) has been considered to establish a classification method of the species, to finally select the most interesting plants which have been further harvested and investigated for their coloring property and dyeing application on natural fibers.

Results

The results showed that local people have accumulated traditional knowledge of dyeing plants, but that this approach had been discontinued in Reunion. The uses of 194 plant species potentially rich in dyes or pigments, belonging to 72 different families, with diverse botanical status (endemic, native, introduced or alien-invasive species) have been recorded. Then, 43 species were harvested and their coloring property were investigated. It demonstrated that dyes extracted from promising species, e.g., Terminalia bentzoe, Weinmannia tinctoria, Thespesia populnea, Erythroxylum laurifolium, Morinda citrifolia, Leea guinensis, Ochrosia borbonica, Danais fragrans, Terminalia cattapa, Casuarina equisetifolia, and Coccoloba uvifera, amongst others, could be used as new textile dyes. Their efficacy in the wool and cotton dyeing has been successfully demonstrated here.

Conclusion

These plant-based dyestuffs showed promising coloring properties with different shades that could meet industrial application requirement. It's an area that could promote local cultural inheritance, create opportunity for business and farmers, and that can make a significant contribution to preserving endangered native species by supporting reforestation schemes. Additional researches are in progress to evaluate the safety of these plant-based colored extracts, their chemical composition and biological activities.
12-Month clinical and radiographic outcomes of ViBone viable bone matrix in patients undergoing cervical and lumbar spinal fusion surgery
Authors: Kim Paul D. , Raiszadeh Ramin , Bomback David A. , Kramer David L. , Moghimi Michael
Published: March 2023

Background

To investigate the clinical safety and efficacy of ViBone® Viable Bone Matrix (VBM), a next generation cellular bone matrix allograft that comprises all three essential bone-forming components: osteogenic, osteoinductive, and osteoconductive factors, and is optimized to enhance cell viability and bone formation.

Methods

This was a multi-center, prospective, post-market study evaluating the safety and efficacy of ViBone VBM in patients undergoing 1–3 level anterior cervical discectomy and fusion or lumbar interbody fusion surgery. Patients were evaluated at baseline, 6-month, and 12-month follow-up clinically and radiographically. Clinical assessment included Visual Analog Scale for pain (VAS-pain), the Neck Disability Index (NDI) for patients with cervical pathologies, and the Oswestry Disability Index (ODI) for patients with lumbar pathologies. Fusion success defined by an independent radiologist was determined radiographically by plain films.

Results

Clinical outcomes evaluated with VAS-pain, NDI, and ODI scales were improved significantly at 6 and 12 months compared to baseline. All patients reached clinically significant improvements at 12 months. There were no adverse events or infections attributed to ViBone VBM. At 12 months, the fusion rate per patient was 88.1% in cervical and 97.6% in lumbar patients, while per-level fusion was 98.5% for cervical and 100% for lumbar segments.

Conclusions

Patients undergoing cervical and lumbar spinal fusion implanted with ViBone VBM demonstrated favorable outcomes at 6 months and 12 months as measured by subjective clinical measures and radiographic fusion rates.

Trial registration This study was registered as NCT03425682 on 1/29/2018.
Clinical outcomes of surgical treatment for end-stage ankle osteoarthritis in patients aged ≥ 75 years: a multicenter, retrospective study
Authors: Amaha Kentaro , Yamaguchi Satoshi , Teramoto Atsushi , Kawasaki Yohei , Shiko Yuki , Kitamura Nobuto
Published: March 2023

Background

This study aimed to clarify the clinical outcomes of surgical treatment for end-stage ankle osteoarthritis in patients aged ≥ 75 years and compare these outcomes with those of patients aged < 75 years.

Methods

A total of 148 patients, including 65 who underwent total ankle arthroplasty and 83 who underwent ankle arthrodesis, were retrospectively surveyed. Clinical outcomes were assessed preoperatively and at the last follow-up using the Japanese Society for Surgery of the Foot Hindfoot Scale and a self-administered foot evaluation questionnaire (SAFE-Q). Patient characteristics, including age, sex, body mass index, radiographic severity, and follow-up period, were also assessed. The patients were divided into older (≥ 75 years) and younger (< 75 years) age groups. Improvements in outcomes were then compared between age groups using univariate analysis and analysis of covariance adjusted for patient characteristics. Total ankle arthroplasty and ankle arthrodesis were analyzed separately.

Results

All clinical outcome scores improved postoperatively in the older age groups for both procedures. Scores for the pain and pain-related subscale of the SAFE-Q improved by 37 points (p < 0.001) in post-total ankle arthroplasty patients and by 35 points in post-ankle arthrodesis patients (p < 0.001). Furthermore, multivariate analysis showed that the improvements observed in all scores were not different between the older and younger age groups for both post-total ankle arthroplasty and post-ankle arthrodesis patients, except for the SAFE-Q physical functioning subscale score for post-ankle arthrodesis patients. The clinical outcomes improved significantly in post-total ankle arthroplasty and post-ankle arthrodesis patients aged ≥ 75 years. Moreover, these improvements were similar to those observed in patients aged < 75 years.

Conclusions

Surgical treatment of end-stage ankle osteoarthritis can be a viable treatment option, even in elderly patients, and can be expected to improve similarly to younger patients.
Diagnostic value of echocardiography combined with serum C-reactive protein level in chronic heart failure
Authors: Zhang Yongxia
Published: March 2023

Background

Chronic heart failure (CHF) is regarded as common clinical heart disease. This study aims to investigate the clinical diagnostic value of echocardiography (Echo) and serum C-reactive protein (CRP) levels in patients with CHF.

Methods

A total of 75 patients with CHF (42 males, 33 females, age 62.72 ± 1.06 years) were enrolled as study subjects, with 70 non-CHF subjects (38 males, 32 females, age 62.44 ± 1.28 years) as controls. The left ventricular ejection fraction (LVEF), fraction shortening rate of the left ventricle (FS), and early to late diastolic filling (E/A) were determined by Echo, followed by an examination of the expression of serum CRP by ELISA. In addition, the Pearson method was used to analyze the correlation between echocardiographic quantitative parameters (EQPs) (LVEF, FS, and E/A) and serum CRP levels. Receiver operating characteristic (ROC) curve was adopted to evaluate the diagnostic efficacy of EQPs and serum CRP levels for CHF. The independent risk factors for CHF patients were measured by logistics regression analysis.

Results

The serum CRP level of CHF patients was elevated, the values of LVEF and FS decreased, and the E/A values increased. ROC curve revealed that the EQPs (LVEF, FS, and E/A) combined with serum CRP had high diagnostic values for CHF patients. Logistic regression analysis showed that the EQPs (LVEF, FS, and E/A) and serum CRP levels were independent risk factors for CHF patients.

Conclusion

Echo combined with serum CRP level has high clinical diagnostic values for CHF patients.
Algorithm-based detection of acute kidney injury according to full KDIGO criteria including urine output following cardiac surgery: a descriptive analysis
Authors: Schmid Nico , Ghinescu Mihnea , Schanz Moritz , Christ Micha , Schricker Severin , Ketteler Markus , Alscher Mark Dominik , Franke Ulrich , Goebel Nora
Published: March 2023

Background

Automated data analysis and processing has the potential to assist, improve and guide decision making in medical practice. However, by now it has not yet been fully integrated in a clinical setting. Herein we present the first results of applying algorithm-based detection to the diagnosis of postoperative acute kidney injury (AKI) comprising patient data from a cardiac surgical intensive care unit (ICU).

Methods

First, we generated a well-defined study population of cardiac surgical ICU patients by implementing an application programming interface (API) to extract, clean and select relevant data from the archived digital patient management system. Health records of N = 21,045 adult patients admitted to the ICU following cardiac surgery between 2012 and 2022 were analyzed. Secondly, we developed a software functionality to detect the incidence of AKI according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria, including urine output. Incidence, severity, and temporal evolution of AKI were assessed.

Results

With the use of our automated data analyzing model the overall incidence of postoperative AKI was 65.4% (N = 13,755). Divided by stages, AKI 2 was the most frequent maximum disease stage with 30.5% of patients (stage 1 in 17.6%, stage 3 in 17.2%). We observed considerable temporal divergence between first detections and maximum AKI stages: 51% of patients developed AKI stage 2 or 3 after a previously identified lower stage. Length of ICU stay was significantly prolonged in AKI patients (8.8 vs. 6.6 days, p <  0.001) and increased for higher AKI stages up to 10.1 days on average. In terms of AKI criteria, urine output proved to be most relevant, contributing to detection in 87.3% (N = 12,004) of cases.

Conclusion

The incidence of postoperative AKI following cardiac surgery is strikingly high with 65.4% when using full KDIGO-criteria including urine output. Automated data analysis demonstrated reliable early detection of AKI with progressive deterioration of renal function in the majority of patients, therefore allowing for potential earlier therapeutic intervention for preventing or lessening disease progression, reducing the length of ICU stay, and ultimately improving overall patient outcomes.

Graphical Abstract
Diurnal variation in declarative memory and the involvement of SCOP in cognitive functions in nonhuman primates
Authors: Shimizu Kimiko , Inoue Ken-ichi , Oishi Takao , Takada Masahiko , Fukada Yoshitaka , Imai Hiroo
Published: March 2023

Cognitive functions depend on the time of day in various organisms. Previously, we found that 24-h recognition memory performance of nocturnal mice changes diurnally through SCOP protein-dependent regulation. It remains unknown whether diurnal change and SCOP-dependent regulation of memory performance are conserved across species with diurnal/nocturnal habits. We tested whether the memory performance of diurnal Japanese macaques depends on the time of day. The memory association between bitter taste of drinking water and the nozzle color of the water bottle was established during the light period of the day to evaluate of memory performance for macaques. Here we found diurnal variation of declarative memory in Japanese macaques. The middle of the daytime is the most effective time for memory performance during the light period. To assess whether SCOP is involved in declarative memory performance, we interfered with SCOP expression by using lentiviral vector expressing shRNA againstScopin the hippocampus of Japanese macaques.Scopknockdown in the hippocampus abrogated the memory performance in the middle of the daytime. Our results implicate that SCOP in the hippocampus is necessary for the diurnal rhythm of the memory system and that the SCOP-dependent memory regulation system may be conserved in mammals.
Optical spectral transmission to assess glucocorticoid therapy response in patients with arthritis: a longitudinal follow-up comparison with joint ultrasound
Authors: Triantafyllias Konstantinos , Marinoska Tatjana , Heller Caroline , de Blasi Michele , Muthuraman Muthuraman , Schwarting Andreas
Published: March 2023

Background

Optical spectral transmission (OST) is a modern diagnostic modality, able to assess the blood-specific absorption of light transmitted through a tissue, promising quantification of inflammation in the finger and wrist joints of patients with arthritis. To date, there are no adequate data regarding the diagnostic value of OST in the evaluation of inflammatory activity changes, during arthritis follow-up.

Objectives of this study were therefore to examine the performance of OST in assessing response to anti-inflammatory therapy in patients with active arthritis and to explore OST associations with clinical, laboratory, and ultrasonographic (US) activity markers.

Methods

1173 joints of 54 patients with arthritides of the wrist and finger joints were examined by OST before and after oral administration of glucocorticoids (GC), during a disease flare. For the same time-points patients underwent clinical, laboratory, and joint US [grayscale (GSUS), power-Doppler (PDUS)] examinations. The distribution of ΔOST-values between the two time-points was compared with the respective distributions of ΔPDUS and ΔGSUS by Bayesian statistical analyses. Moreover, the diagnostic performance of OST compared to a control group (2508 joints of 114 subjects) was examined by receiver operating characteristics and associations of OST values with clinical, laboratory, and arthrosonographic parameters were evaluated by correlation analyses.

Results

OST and US performed similarly in the assessment of inflammatory changes caused by GC (same value-change tendency in 83.2% of the cases). Bayesian statistics revealed no significant differences between ΔOST and ΔPDUS for all 3 examined joint categories (accuracy: metacarpophalangeal (MCP): 68.1%; proximal interphalangeal (PIP): 60.4%; wrists: 50.4%) and between ΔOST and ΔGSUS for MCP and PIP joints (accuracy: 51.1% and 78.7%, respectively). OST diagnostic performance (patients vs. controls) was excellent in both time-points [area under the curve (AUC) before GC=0.883(95%CI=0.83–0.94) and after GC=0.811(95%CI=0.74–0.881); p<0.001]. Furthermore, OST correlated significantly with all examined sonographic activity scores (all; p<0.001) and with swollen joint counts (p<0.01).

Conclusions

OST was able to assess response to therapy in a similar way to joint US and correlated significantly with arthritis activity markers. Therefore, OST has proved to be a valuable tool to assist disease activity monitoring in the examined cohort.

Trial registration

German Registry of Clinical Trials, DRKS00016752
Mouse models of systemic juvenile idiopathic arthritis and macrophage activation syndrome
Authors: Inoue Natsumi , Schulert Grant S.
Published: March 2023

Macrophage activation syndrome (MAS) is a life-threatening complication of pediatric rheumatic diseases, occurring most commonly in children with systemic juvenile idiopathic arthritis (SJIA). Despite several classes of currently available treatment options for SJIA, including biologic agents targeting IL-1 or IL-6, there remain severe cases suffering from refractory disease and recurrent MAS. The phenotype of MAS is similar to hemophagocytic lymphohistiocytosis (HLH), but the underlying pathophysiology of MAS complicating SJIA or other disorders has not been fully clarified. These facts make it challenging to develop and utilize animal models to study MAS. To date, there is no “perfect” model replicating MAS, but several models do demonstrate aspects of SJIA and/or MAS. In this review, we examine the proposed animal models of SJIA and MAS, focusing on how they reflect these disorders, what we have learned from the models, and potential future research questions. As we better understand the key features of each, animal models can be powerful tools to further define the pathophysiology of SJIA and MAS, and develop new treatment targets and strategies.
Association of prognostic nutritional index level and diabetes status with the prognosis of coronary artery disease: a cohort study
Authors: Li Tianyu , Yuan Deshan , Wang Peizhi , Zeng Guyu , Jia Sida , Zhang Ce , Zhu Pei , Song Ying , Tang Xiaofang , Gao Runlin , Xu Bo , Yuan Jinqing
Published: March 2023

Background

Malnutrition and inflammation are associated with adverse clinical outcomes in patients with diabetes or coronary artery disease (CAD). Prognostic nutritional index (PNI) is a comprehensive and simple indicator reflecting nutritional condition and immunological status. Whether there is a crosstalk between nutritional-immunological status and diabetes status for the impact on the prognosis of coronary artery disease (CAD) is unclear.

Methods

A total of 9429 consecutive CAD patients undergoing percutaneous coronary intervention were grouped by diabetes status [diabetes (DM) and non-diabetes (non-DM)] and preprocedural PNI level [high PNI (H-PNI) and low PNI (L-PNI)] categorized by the statistically optimal cut-off value of 48.49. The primary endpoint was all-cause death.

Results

During a median follow-up of 5.1 years (interquartile range: 5.0–5.1 years), 366 patients died. Compared with the non-DM/H-PNI group, the DM/L-PNI group yielded the highest risk of all-cause death (adjusted hazard ratio: 2.65, 95% confidence interval: 1.97–3.56, p < 0.001), followed by the non-DM/L-PNI group (adjusted hazard ratio: 1.44, 95% confidence interval: 1.05–1.98, p = 0.026), while DM/H-PNI was not associated with the risk of all-cause death. The negative effect of L-PNI on all-cause death was significantly stronger in diabetic patients than in nondiabetic patients (p for interaction = 0.037). Preprocedural PNI category significantly improved the Global Registry of Acute Coronary Events (GRACE) risk score for predicting all-cause death in patients with acute coronary syndrome, especially in those with diabetes.

Conclusions

CAD patients with diabetes and L-PNI experienced the worst prognosis. The presence of diabetes amplifies the negative effect of L-PNI on all-cause death. Poor nutritional-immunological status outweighs diabetes in increasing the risk of all-cause death in CAD patients. Preprocedural PNI can serve as an assessment tool for nutritional and inflammatory risk and an independent prognostic factor in CAD patients, especially in those with diabetes.
Luteolin intake is negatively associated with all-cause and cardiac mortality among patients with type 2 diabetes mellitus
Authors: Zhang Wenbin , Li Duanbin , Shan Yu , Tao Yecheng , Chen Qingqing , Hu Tianli , Gao Menghan , Chen Zhezhe , Jiang Hangpan , Du Changqin , Wang Min , Guo Kai
Published: March 2023

Background

Luteolin, a common flavonoid in our daily diet, has potent anti-diabetic effects. However, its prognostic impact on type 2 diabetes mellitus (T2DM) is still uncertain. This study aimed to clarify this association.

Methods

In this prospective cohort study, 2,461 patients with T2DM were included from the National Health and Nutrition Examination Survey. Dietary luteolin intake was estimated by the type and amount of food consumed in a 24-hour dietary recall. All-cause and cardiac mortality were ascertained by National Death Index Mortality data (as of December 31, 2019). The association of luteolin intake with mortality risk was estimated by Cox proportional hazards model.

Results

The median (interquartile range) luteolin intake was 0.355 (0.130, 0.835) mg/day. During the follow-up (median, 8.4 years), 561 all-cause deaths (including 136 cardiac deaths) were documented. Per-unit increment of luteolin intake (natural logarithm transformed) was found to reduce all-cause mortality by 7.0% (P = 0.024) and cardiac mortality by 22.6% (P = 0.001) in patients with T2DM. An inverse dose-response association was identified between luteolin intake (range: 0.005–9.870 mg/day) and mortality risk. The consistent result was also shown when stratified by age, gender, race, body mass index, HbA1c level, and T2DM duration. Moreover, luteolin intake increment was also shown to be associated with a lower C-reactive protein level at baseline (β =-0.332; 95% CI =-0.541, -0.122).

Conclusion

The current study confirmed that the dietary luteolin intake increment reduced all-cause mortality (especially cardiac mortality) in patients with T2DM, which may be attributed to the anti-inflammatory property of luteolin.

Graphical abstract