bluuebunny/crossref_metadata_2025 huggingface dataset:
Neighborhood ‘Disamenities’: local barriers and cognitive function among Black and white aging adults
Authors: Yu Wenshan , Esposito Michael , Li Mao , Clarke Philippa , Judd Suzanne , Finlay Jessica
Published: January 2023

Background

This study examined the association between cognitive function and three neighborhood ‘disamenities’ that may pose local barriers to utilizing community resources and increase risk for cognitive decline.

Method

Using national data from 21,165 urban- and suburban-dwelling Black and white adults (mean age: 67 years) in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study, we assessed global cognitive function through a factor score of five cognitive screening tests. General Additive Mixed Models (GAMM) tested whether residing in areas with more polluting sites, highways, and limited walkability was associated with worse cognitive function.

Results

Limited walkability and the presence of polluting sites had a significant negative association with cognitive function after controlling for individual and neighborhood factors.

Conclusion

Neighborhood disamenities may be linked to cognitive function among aging residents. Identifying neighborhood factors that pose barriers to accessing community resources may inform upstream policy applications to reduce risk for cognitive decline.
Does physical activity mediate the associations between blue space and mental health? A cross-sectional study in Australia
Authors: Murrin Emma , Taylor Nicole , Peralta Louisa , Dudley Dean , Cotton Wayne , White Rhiannon Lee
Published: January 2023

Background

Research has begun to examine whether blue space is beneficial to mental health. While results are promising, it is difficult to know which aspects of mental health or mental ill-health may benefit most. Physical activity has been proposed as one potential mechanism via which blue space may be associated with better mental health. However, very few studies have examined mechanisms. We examined associations between blue space proximity and a range of mental health outcomes and examined which of these associations were mediated by physical activity.

Methods

350 participants (M = 38.74, SD = 14.92, 70% female) self-reported their weekly physical activity and completed measures of depression, anxiety, and psychological wellbeing. We then used GIS software to calculate blue space proximity (i.e., coastal and inland), and structural equation modelling with mediation paths to determine the role of physical activity in the associations between bluespace and mental health.

Results

Physical activity partially mediated the associations between coastal proximity and depression (β = 0.02, 95% CI = 0.001, 0.05), anxiety (β = 0.03, 95% CI = 0.01, 0.06), and wellbeing (β = − 0.03, 95% CI = − 0.08, − 0.01), and fully mediated the associations between inland water proximity and depression (β = 0.02, 95% CI = 0.003, 0.05), anxiety (β = 0.03, 95% CI = 0.01, 0.07), and wellbeing (β = − 0.03, 95% CI = − 0.07, − 0.01).

Conclusion

While physical activity appears to explain associations between inland blue space and mental health outcomes, it only partially explains the association between coastal blue space and mental health, suggesting other mechanisms may play a role and even inactive exposure may be beneficial.
The forms and adverse effects of insecurities among internally displaced children in Ethiopia
Authors: Kemei Janet , Salami Bukola , Soboka Matiwos , Gommaa Hayat Imam Mohamed , Okeke-Ihejirika Philomina , Lavin Tina
Published: January 2023

Background

Ethiopia has seen an increase in the number of internally displaced persons (IDPs) due to conflict and violence related to border-based disputes and climate change. This study examines the insecurities experienced by IDPs in the Burayu camp and how they navigate and challenge them. Violence and insecurity have daunted Ethiopian regions for decades, violated children’s rights, and impeded the achievement of the United Nation’s sustainable development goals related to children, such as good healthcare and mental health, quality education, clean water, and sanitation. The deteriorating security concerns in Ethiopia could also expose IDP children to poor health outcomes associated with a lack of access to healthcare services.

Methods

This was an exploratory qualitative case study guided by intersectionality theoretical lens to explore the forms of insecurities perceived and experienced by IDPs in Ethiopia. Participants were selected using a purposeful sampling approach. We interviewed 20 children, 20 parents or guardians, and 13 service providers. Interviews were audio recorded and transcribed verbatim in Afan Oromo, then translated into English. We used NVivo 12 qualitative data analysis software to analyze data following Braun & Clarke’s approach to thematic data analysis.

Results

The participants reported that IDP children in Burayu town faced many challenges related to poor socioeconomic conditions that exposed them to several insecurities and negatively affected their well-being. They reported inadequate access to clothing and shelter, clean water, sanitary facilities, food, and adequate healthcare due to financial barriers, lack of drugs, and quality of care. Our data analysis shows that socioeconomic and contextual factors intersect to determine the health and well-being of children in the Ethiopian IDP camp studied. The children experienced insecurities while navigating their daily lives. This is compounded by institutional practices that shape gender relations, income status, and access to healthcare, education, and food. These deficiencies expose children to traumatic events that could decrease future livelihood prospects and lead to compromised mental health, rendering them susceptible to prolonged post-traumatic stress disorder and depression. Results are presented under the following topics: (1) basic needs insecurity, (2) healthcare insecurity, (3) academic insecurity, (4) economic insecurity, (5) food insecurity, and (6) physical and mental health insecurity.

Conclusion

Successful relocation and reintegration of IDPs would help to alleviate both parent and child post-conflict stressors. Managing and following up on economic reintegration efforts is needed in both the short and long term. Such measures will help to achieve goals for specific projects attached to donor support outcomes, consequently enabling social support and conflict resolution management efforts.
“COVID gave him an opportunity to tighten the reins around my throat”: perceptions of COVID-19 movement restrictions among survivors of intimate partner violence
Authors: Wyckoff Kathryn G. , Narasimhan Subasri , Stephenson Kaylee , Zeidan Amy J. , Smith Randi N. , Evans Dabney P.
Published: January 2023

Background

Intimate Partner Violence (IPV) poses a serious public health threat globally and within the United States. Preliminary evidence highlighted surges in IPV during the COVID-19 pandemic. The pandemic offers a unique context, with many states and countries enacting movement-restrictions (i.e., shelter-in-place orders) that exacerbated IPV. Although these movement restrictions and other infection control methods (i.e., isolation, quarantine orders) have proven successful in reducing the spread of COVID-19, their impacts on IPV have not been thoroughly investigated. Specifically, public health measures restricting movement reinforce and socially legitimize isolation and coercive control tactics enacted by perpetrators of abuse. The purpose of this study was to understand the impacts of COVID-19, including the impacts of movement restrictions (i.e., shelter in place orders, quarantine, isolation orders) on experiences of IPV from the perspective of survivors.

Methods

In-depth interviews were conducted with ten survivors who presented at a large, public hospital or sought community IPV resources (i.e., domestic violence shelter, therapy services) in Atlanta, Georgia between March and December 2020. Thematic analysis was carried out to describe the impact of COVID-19 movement restrictions on IPV and help-seeking behaviors among survivors, in addition to identifying resources to improve IPV response during pandemics.

Results

Through discussion of their experiences, survivors indicated how movement restrictions, social distancing measures, and the repercussions of the pandemic influenced their relationship challenges, including the occurrence of new or a higher frequency and/or severity of IPV episodes. Survivors cited relationship challenges that were amplified by either movement restrictions or consequences of COVID-19, including reinforced control tactics, and increased financial or life stressors resulting from the pandemic. COVID-19 movement restrictions catalyzed new relationships quickly and sparked new or intensified violence in existing relationships, revealing gaps in IPV support services.

Conclusion

These findings suggest COVID-19 movement restrictions and social distancing measures amplify IPV and experiences of trauma due to new or exacerbated relationship challenges. Further, results highlight how partners cited COVID-19 movement restrictions to justify methods of coercive control. Public health professionals engaged in pandemic preparedness must give serious consideration to how social distancing measures may amplify trauma in those experiencing IPV.
A new approach to enter Retzius space in laparoscopic transabdominal preperitoneal bilateral inguinal hernia repair
Authors: Tian Lifei , Zhang Le , Li Zeyu , Yan Likun , Wang Xiaoqiang
Published: January 2023

Background

To investigate the feasibility, safety and efficacy of the right-side approach to enter Retzius space in laparoscopic transabdominal preperitoneal bilateral inguinal hernia repair.

Methods

Retrospective analysis was performed on 189 patients who were diagnosed with bilateral inguinal hernia preoperatively or intraoperatively and underwent selective TAPP in the General Surgery I Section of Shaanxi Provincial People’s Hospital from January 2015 to September 2020. 94 cases were performed using the right-side approach (research group), and 95 cases with conventional approach (control group). Intraoperative and postoperative conditions of the two groups were observed and compared.

Results

All operation were completed successfully. The operative time of research group was significantly shorter than that of control group (128.8 ± 35.4 vs 144.1 ± 40.9 min, P = 0.006). There were no significant differences in postoperative hospital stay, VAS score on first postoperative day, incidence of seroma and hematoma, urinary retention and other complications (P > 0.05). None of the patients occured hernia recurrence, mesh infection, intestinal obstruction and other complications.

Conclusions

The right-side approach to enter Retzius space is safe and feasible in TAPP surgery of bilateral inguinal hernia. Compared with the conventional approach, it can shorten the operative time and has certain advantages.
Individual, familial and country-level factors associated with oral hygiene practices in children: an international survey
Authors: Elkhodary Heba Mohamed , Abdelnabi Mohamed Hussein , Swelem Amal Ali , Sabbagh Heba Jafar , El Meligy Omar Abd El Sadek , Talaat Iman Mamdouh , Abdellatif Enas B. , Khader Yousef , Al-Batayneh Ola B. , Al-Khanati Nuraldeen Maher , Nurelhuda Nazik M. , Alhabli Sara , Mostafa Mohamed Hassan , Qureshi Shabnum , Qureshi Nafeesa , Yousaf Muhammad Abrar , Taha Dunia , Marafi Yousef Falah , Al Harrasi Sharifa Nasser , Al-Rai Sarah , Gomaa Noha , Mattar Hala , Bakhaider Hanin A. , Samodien Bahia , Lố Hanane , El Tantawi Maha
Published: January 2023

Background

Maintaining good oral hygiene is key to preventing dental caries and periodontal disease. Children and adolescents with good oral hygiene behaviours are likely to grow into adults with the same behaviours. This study assessed the frequency of using various oral hygiene methods among children and adolescents from different countries and individual, familial and country-level factors associated with the use of these methods.

Methods

A multi-country online survey collected data from caregivers of children in 2020–21 about children’s use of oral hygiene methods including toothbrush, fluoridated toothpaste, mouthwash, dental floss and miswak using self-administered, close-ended questions. Adjusted multilevel logistic regression models were used to assess the relationship between each of the five oral hygiene methods (dependent variables) and the independent factors: sex, age, and history of dental visits (individual factors), mother's education and area of residence (familial factors) as well as country income and region (country-level factors).

Results

A total of 4766 parents/caregivers were included from 20 countries (77.4% Eastern Mediterranean-region and 41.6% lower middle income countries). The most frequent oral hygiene methods were using toothbrush and toothpaste (90% and 60.3%). The use of oral hygiene methods differed by age, sex and history of dental visits as well as mother’s education and area of residence (P < 0.05). In addition, children from low income countries had significantly lower odds of using mouthwashes and dental floss than those from high income countries (AOR = 0.55, 95% CI 0.31, 0.98 and AOR = 0.34, 95% CI 0.12, 0.97) whereas children from the European region had higher odds of using mouthwash (AOR = 2.82, 95% CI 1.27, 6.26) and those from the region of the Americas had higher odds of using dental floss (AOR = 3.84, 95% CI 1.28, 11.52) than those from the Eastern Mediterranean region.

Conclusions

The use of various oral hygiene methods is associated with individual, familial and country-level factors. Oral health promotion programs should be developed taking into account these influences.
Dentoalveolar, skeletal, pharyngeal airway, cervical posture, hyoid bone position, and soft palate changes with Myobrace and Twin-block: a retrospective study
Authors: Çoban Büyükbayraktar Zeynep , Camcı Hasan
Published: January 2023

Background

The primary aim of this study was to evaluate the dentoalveolar, skeletal, pharyngeal airway, cervical posture, hyoid bone position, and soft palate effects of the Myobrace and Twin-block appliances. The second was to compare them in terms of ease of use by assessing the factors that may influence patient compliance.

Methods

The study included thirty-six Class II division 1 patients (19 females, 17 males; mean age, 12.14 ± 1.23) who had previously been treated in the Orthodontic Clinic at Sivas Cumhuriyet University Faculty of Dentistry. The patients were divided into two groups: Group 1: Myobrace (n = 18), and Group 2: twin block (n = 18). The effects of the appliances on the skeletal, dentoalveolar, soft tissue, craniocervical, and other anatomic structures were assessed using 46 measurements (22 linear and 24 angular), on pre and post-treatment cephalometric radiographs. AudaxCeph 5.0 software (Ljubljana, Slovenia) was used for the analysis. To analyze the changes after one year of treatment, a paired sample t-test and Wilcoxon signed-rank test were used. Intergroup comparison was performed using the Student t-test and the Mann–Whitney U test.

Results

In the Myobrace and Twin-block groups, there was a significant increase in SNB (°) (p = 0.004,p = 0.001), IMPA (°) (p = 0.005,p = 0.001) and a significant drop in U1/SN (°) (p = 0.021,p = 0.005). The lengths of Cd–Gn (mm), Go–Pg (mm), and Cd–Go (mm) increased significantly in the Twin-block group (p = 0.003,p = 0.010,p = 0.001), whereas the Myobrace group did not change. Similarly, there was no significant difference in pharyngeal and soft palate measurements in the Myobrace group but a statistically significant decrease in SP length and angle in the Twin-block group (p = 0.001,p = 0.006). Increases in SN/OPT (°) (p = 0.032,p = 0.001) and SN/CVT (°) (p = 0.012,p = 0.001) were statistically significant in both groups. Myobrace was more difficult to use while sleeping, whereas the twin block caused more nausea.

Conclusions

Both appliances can be used for mandibular advancement. The Twin-block appliance, on the other hand, was more effective and patient-friendly.
Work experience was associated with the knowledge and practice of catheter-associated urinary tract infection prevention among nurses at University of Gondar Comprehensive Specialized Hospital, northwest Ethiopia, 2021
Authors: Zegeye Alebachew Ferede , Kassahun Chanyalew Worku , Temachu Yemataw Zewdu
Published: January 2023

Background

Catheter-associated urinary tract infection is the source of about 20% of episodes of health-care acquired infections in acute care facilities and it is over 50% in long-term care facilities. In Ethiopia, there is no published scientific research regarding knowledge and practice of nurses on catheter-associated urinary tract infections prevention. Therefore, this study aimed to assess knowledge, practice and associated factors of CAUTI prevention among nurses working at university of Gondar comprehensive specialized hospital, northwest Ethiopia, 2021.

Methods

Institutional based cross sectional study was conducted at University of Gondar Comprehensive Specialized Referral Hospital from April 01 to May 01, 2021 among 423 nurses. Simple random sampling technique was used. Data were collected by using self-administered questionnaire then coded and entered into EPI- Data version 4.6 and then exported to SPSS version 23. Descriptive statistics was computed, and the result was summarized by texts, tables, and charts. All variables with P-value < 0.25 in the univariate analysis were included in the multivariable regression analysis. The degree of association was interpreted by using the adjusted odds ratio with 95% confidence intervals.

Results

Good knowledge and practice of nurses towards CAUTI prevention was 37.7% and 51.8% respectively. Good knowledge was associated with sex [AOR = 1.84, 95% CI (1.09, 3.11)], work experience [AOR = 2.36, 95% CI (1.09, 5.10)], working unit [AOR = 6.9, 95% CI (2.11, 22.52)], training [AOR = 2.33, 95% CI (1.17, 4.65)] and had guideline [AOR = 2.78, 95% CI (1.59, 4.88)]. Good practice was associated with sex, work experience, attitude and knowledge towards CAUTI prevention [AOR = 2.19, 95% CI (1.23, 3.88)], [AOR = 5.44, 95% CI (1.66, 17.84)], [AOR = 3.06, 95% CI (1.65, 5.67)], and [AOR = 5.28, 95% CI (2.86, 9.76)] respectively.

Conclusions

Nearly one-third of nurses had good knowledge and more than half of nurses had good practice towards CAUTI prevention. Sex, work experience, work unit, presence of guideline, and training were significantly associated with knowledge. Sex, work experience, good attitude and, knowledge were associated with practice of nurses towards CAUTI prevention. The knowledge and practice towards catheter associated urinary tract infection prevention among nurses should be increased, so that the patients could enjoy and maintain the healthy lifestyle.
Clinical potential of inclisiran for patients with a high risk of atherosclerotic cardiovascular disease
Authors: Nishikido Toshiyuki
Published: January 2023

Elevated low-density lipoprotein cholesterol (LDL-C) level is associated with an increased risk of atherosclerotic cardiovascular disease. Although high-intensity lipid-lowering therapies with statins and ezetimibe are highly effective for reducing LDL-C levels, over half of high-risk patients do not achieve guideline-recommended LDL-C goals. Thus, there is a significant gap between treatment guidelines and their implementation in daily clinical practice. The major causes are individual variability in the response to lipid-lowering therapies and variation in treatment adherence. Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies combined with statins provide marked and consistent reduction in LDL-C levels; however, poor adherence due to the need for subcutaneous injections every 2 or 4 weeks and high cost are major obstacles to their use in real-world clinical settings. Inclisiran, a recently approved novel small interfering ribonucleic acid (siRNA) molecule that inhibits PCSK9 synthesis, provides robust and long-term reduction in LDL-C levels with a low inter-individual variability in the LDL-C-lowering response. Moreover, its administration by biannual injection is expected to greatly improve treatment adherence. Clinical trials of this drug lasting for up to 4 years showed acceptable safety profiles, and ongoing studies accumulate evidence of its longer-term safety. This narrative review summarizes the available evidence on the efficacy and safety of inclisiran and analyzes its potential to overcome the gap between guideline recommendations and real-world clinical practice in current LDL-C-lowering therapies, with a focus on reduced LDL-C level variability and improved treatment adherence.
Association between triglyceride-glucose index and risk of cardiovascular disease among postmenopausal women
Authors: Liu Qian , Si Fei , Liu Zhou , Wu Yuntao , Yu Jing
Published: January 2023

Objective

We aimed to examine the association of triglyceride-glucose index (TyG) with risk for cardiovascular disease (CVD) among postmenopausal women.

Methods

A total of 7741 participants met the inclusion criteria, and were included in the analysis. The TyG index was calculated as ln (triglyceride [mg/dL] × fasting blood glucose [mg/dL]/2). The participants were classified into four groups by the quartiles of TyG index, and the Q1 group was used as the reference group. The cumulative incidence of CVD for the groups were compared using the Kaplan–Meier curves. The association between the TyG index and risk of CVD among postmenopausal women was assessed by the Cox proportional hazards models (hazard ratio [HR], 95% confidence intervals [CI]).

Results

During a median follow-up of 12 years, a total of 383 (4.95%) participants developed incident CVD. After adjusting for potential confounding factors, a high baseline TyG index (Q4 group) was associated with higher future risk of CVD, the HR (95% CI) of CVD risk was 1.70 (1.21–2.38) in Q4 group compared with the Q1 group. Subgroup analyses showed the Q4 group was significantly associated with the risk of CVD, regardless of age at menopause (younger than 50 years; 50 years and older) and obesity status.

Conclusions

Higher TyG index at baseline as a marker of insulin resistance (IR), is associated with higher risk of future CVD among postmenopausal women. The TyG index may serve as a simple and easy marker for early identification of high-risk individuals in the postmenopausal women.
New insights on the interaction between m6A modification and non-coding RNA in cervical squamous cell carcinoma
Authors: Shen Guqun , Li Fen , Wang Yan , Huang Yongmei , Aizezi Gulibiya , Yuan Jinrui , Ma Cailing , Lin Chen
Published: January 2023

Background

N6-Methyladenosine (m6A) and long non-coding RNAs (lncRNAs) are both crucial regulators in human cancer growth and metastasis. However, their regulation on cervical squamous cell carcinoma (CSCC) is largely unclear. The present study aimed to explore the role of m6A-associated lncRNAs in CSCC.

Methods

We screened the expression of methylation modification-related enzymes in CECC samples from TCGA. The qRT-PCR was used to detect METTL3 and lncRNA METTL4-2 expression. The biological activities of METTL3 in CSCC cells were evaluated by CCK-8, colony formation, transwell, wound healing, and xenograft tumor assays, respectively. The SRAMP tool was used to screen m6A modification sites of METTL4-2. Finally, the quantitative analysis of m6A modification was carried out by MeRIP.

Results

METTL3 expression was upregulated in CSCC cells and tissues. Biological function and function loss analysis indicated that METTL3 promoted the migration and proliferation of CSCC cells. In addition, METTL3 promoted CSCC tumor growth in vivo. Mechanically, METTL3 installed the m6A modification and enhanced METTL4-2 transcript stability to increase its expression. Meanwhile, the m6A “reader” YTHDF1 recognized METTL4-2 installed by METTL3 and facilitated the translation of METTL4-2.

Conclusions

In conclusion, our study highlights the function and mechanism of METTL3-induced METTL4-2 in CSCC. These findings support that METTL3-stabilized METTL4-2 promoted CSCC progression via a m6A-dependent modality, which provides new insights into therapeutic strategies for CSCC.
Impact of the gut microbiota and associated metabolites on cardiometabolic traits, chronic diseases and human longevity: a Mendelian randomization study
Authors: Gagnon Eloi , Mitchell Patricia L. , Manikpurage Hasanga D. , Abner Erik , Taba Nele , Esko Tõnu , Ghodsian Nooshin , Thériault Sébastien , Mathieu Patrick , Arsenault Benoit J.
Published: January 2023

Features of the gut microbiota have been associated with several chronic diseases and longevity in preclinical models as well as in observational studies. Whether these relations underlie causal effects in humans remains to be established. We aimed to determine whether the gut microbiota influences cardiometabolic traits as well as the risk of chronic diseases and human longevity using a comprehensive 2-Sample Mendelian randomization approach. We included as exposures 10 gut-associated metabolites and pathways and 57 microbial taxa abundance. We included as outcomes nine cardiometabolic traits (fasting glucose, fasting insulin, systolic blood pressure, diastolic blood pressure, HDL cholesterol, LDL cholesterol, triglycerides, estimated glomerular filtration rate, body mass index [BMI]), eight chronic diseases previously linked with the gut microbiota in observational studies (Alzheimer’s disease, depression, type 2 diabetes, non-alcoholic fatty liver disease, coronary artery disease (CAD), stroke, osteoporosis and chronic kidney disease), as well as parental lifespan and longevity. We found 7 associations with evidence of causality before and after sensitivity analyses, but not after multiple testing correction (1198 tests). Most effect sizes (4/7) were small. The two largest exposure-outcome effects were markedly attenuated towards the null upon inclusion of BMI or alcohol intake frequency in multivariable MR analyses. While finding robust genetic instruments for microbiota features is challenging hence potentially inflating type 2 errors, these results do not support a large causal impact of human gut microbita features on cardiometabolic traits, chronic diseases or longevity. These results also suggest that the previously documented associations between gut microbiota and human health outcomes may not always underly causal relations.
Pan-cancer onco-signatures reveal a novel mitochondrial subtype of luminal breast cancer with specific regulators
Authors: Simeone Ines , Ceccarelli Michele
Published: January 2023

Background

Somatic alterations in cancer cause dysregulation of signaling pathways that control cell-cycle progression, apoptosis, and cell growth. The effect of individual alterations in these pathways differs between individual tumors and tumor types. Recognizing driver events is a complex task requiring integrating multiple molecular data, including genomics, epigenomics, and functional genomics. A common hypothesis is that these driver events share similar effects on the hallmarks of cancer. The availability of large-scale multi-omics studies allows for inferring these common effects from data. Once these effects are known, one can then deconvolve in every individual patient whether a given genomics alteration is a driver event.

Methods

Here, we develop a novel data-driven approach to identify shared oncogenic expression signatures among tumors. We aim to identify gene onco-signature for classifying tumor patients in homogeneous subclasses with distinct prognoses and specific genomic alterations. We derive expression pan-cancer onco-signatures from TCGA gene expression data using a discovery set of 9107 primary pan-tumor samples together with respective matched mutational data and a list of known cancer-related genes from COSMIC database.

Results

We use the derived ono-signatures to state their prognostic significance and apply them to the TCGA breast cancer dataset as proof of principle of our approach. We uncover a “mitochondrial” sub-group of Luminal patients characterized by its biological features and regulated by specific genetic modulators. Collectively, our results demonstrate the effectiveness of onco-signatures-based methodologies, and they also contribute to a comprehensive understanding of the metabolic heterogeneity of Luminal tumors.

Conclusions

These findings provide novel genomics evidence for developing personalized breast cancer patient treatments. The onco-signature approach, demonstrated here on breast cancer, is general and can be applied to other cancer types.
ADAM12 promotes clear cell renal cell carcinoma progression and triggers EMT via EGFR/ERK signaling pathway
Authors: Xu Jinming , Wang Yan , Jiang Jiahao , Yin Cong , Shi Bentao
Published: January 2023

Background

Clear cell renal cell carcinoma (ccRCC) is a major worldwide health problem due to its high prevalence and mortality rate. A disintegrin and metalloproteinase 12 (ADAM12) is aberrantly expressed in various cancers and plays an important role in tumor progression. However, its explicit effect and molecular mechanism in ccRCC remain unclear.

Methods

We investigated the dysregulation of ADAM12 in ccRCC through public databases and bioinformatics analyses. The expression of ADAM12 was further verified in ccRCC tissues by RT-qPCR and immunohistochemistry (IHC). The relationship between ADAM12 expression and clinicopathological characteristics was analyzed statistically. The effects of ADAM12 on the proliferation, migration and invasion of ccRCC cells were examined by in vitro and in vivo experiments.

Results

ADAM12 was significantly upregulated in ccRCC tissues and associated with poor prognosis in ccRCC patients. ADAM12 promoted ccRCC cell proliferation, migration and invasion in vitro and the growth of subcutaneous tumors in vivo. Knockdown of ADAM12 successfully suppressed its oncogenic function. Mechanistically, its overexpression induced epithelial-mesenchymal transition (EMT) by downregulating E-cadherin and upregulating N-cadherin and Snail. Moreover, ADAM12 participated in the epidermal growth factor receptor (EGFR) pathway and activated the downstream signal ERK1/2 by shedding the EGFR ligand, thereby upregulating target genes including c-Myc, enhancing cell survival and invasion ability, and promoting tumor progression, metastasis and the induction of EMT.

Conclusions

High expression of ADAM12 induced EMT and promoted cell proliferation, migration, and invasion by activating the EGFR/ERK signaling pathway in ccRCC.
The presence of cerebellar B cell aggregates is associated with a specific chemokine profile in the cerebrospinal fluid in a mouse model of multiple sclerosis
Authors: Schropp Verena , Chunder Rittika , Dietel Barbara , Tacke Sabine , Kuerten Stefanie
Published: January 2023

Background

The presence of meningeal ectopic lymphoid structures (ELS) in a subgroup of patients diagnosed with secondary progressive multiple sclerosis (SPMS) corresponds to a pronounced cortical inflammation and an aggravated disease course. In MP4-induced experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS), B cell aggregates develop in the central nervous system (CNS) in the chronic stage of the disease. Therefore, the model is suitable for studying key molecules of ELS development and maintenance. Here, we investigated whether there is a specific cytokine and chemokine signature in paired cerebrospinal fluid (CSF) and serum samples associated with the presence of cerebellar B cell and T cell pathology and B cell aggregates of MP4-immunized mice.

Methods

Paired CSF and serum samples were collected from the cisterna magna and periphery of MP4-immunized mice at the chronic stage of disease. A control group with mice immunized only with the adjuvant (vehicle) was included in the study. A selected panel of 34 cytokines and chemokines were measured by MAGPIX® for both cohorts. For the assessment of B cell and T cell infiltration, immunohistochemical staining was performed and analyzed using light microscopy. To detect specific chemokine receptors additional staining was conducted.

Results

While we detected several upregulated cytokines and chemokines in the CSF of MP4-immunized mice independent of the extent of B cell and T cell pathology compared to vehicle-immunized mice, C-C motif chemokine ligand (CCL)-1 was associated with high B cell and T cell infiltration. Furthermore, the level of certain chemokines, including CCL1, CCL5, CCL7, CCL12, CCL22 and C-X-C motif chemokine ligand (CXCL)-13, was significantly increased (p < 0.05) in MP4-immunized mice showing a high number of B cell aggregates. While C-C motif chemokine receptor (CCR)5 had a ubiquitous expression independent of the extent of B cell and T cell pathology, C-X-C motif chemokine receptor (CXCR)-5 and CXCR6 expression was specifically associated with high B cell and T cell pathology.

Conclusion

Our data suggest that multiple cytokines and chemokines are involved in the pathophysiology of MP4-induced EAE. Furthermore, the presence of B cell aggregates was associated with a specific chemokine profile in the CSF, which might be useful for predicting the presence of these aggregates without the necessity to histologically screen the CNS tissue.
Nanoparticulate MgH2 ameliorates anxiety/depression-like behaviors in a mouse model of multiple sclerosis by regulating microglial polarization and oxidative stress
Authors: Li Zhenghao , Chen Kefu , Shao Qi , Lu Hongtao , Zhang Xin , Pu Yingyan , Sun Xuejun , He Hua , Cao Li
Published: January 2023

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS). Anxiety and depression are the most common psychiatric comorbidities of MS, which seriously affect patients’ quality of life, treatment compliance, and prognosis. However, current treatments for anxiety and depression in MS show low therapeutic efficacy and significant side effects. In the present study, we explored the therapeutic effects of a novel low-toxic anti-inflammatory drug, nanoparticulate magnesium hydride (MgH2), on mood disorders of MS. We observed that anxiety/depression-like behaviors in experimental autoimmune encephalomyelitis (EAE) mice were alleviated by MgH2 treatment. In addition, disease severity and inflammatory demyelination were also diminished. Furthermore, we confirmed the suppressive effect of MgH2 on depression in the acute restraint stress model. Mechanistically, MgH2 may play a therapeutic role by promoting microglial M2 polarization, inhibiting microglial M1 polarization, and reducing oxidative stress and mitochondrial damage. Therefore, nanoparticulate MgH2 may be a promising therapeutic drug for psychiatric comorbidities of MS.
Mitochondrial DNA and inflammatory proteins are higher in extracellular vesicles from frail individuals
Authors: Byappanahalli Anjali M. , Noren Hooten Nicole , Vannoy Mya , Mode Nicolle A. , Ezike Ngozi , Zonderman Alan B. , Evans Michele K.
Published: January 2023

Background

Frailty, a clinical syndrome commencing at midlife, is a risk for morbidity and mortality. Little is known about the factors that contribute to the chronic inflammatory state associated with frailty. Extracellular vesicles (EVs) are small, membrane-bound vesicles that are released into the circulation and are mediators of intercellular communication. We examined whether mitochondrial DNA (mtDNA) and inflammatory proteins in EVs may act as damage-associated molecular pattern (DAMP) molecules in frailty.

Results

To address whether EVs and their associated mtDNA and inflammatory protein cargo are altered with frailty, EVs were isolated from non-frail (n = 90) and frail (n = 87) middle-aged (45–55 years) participants from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. EV concentration was highest in frail White participants. EV mtDNA levels were significantly higher in frail individuals compared to non-frail individuals. The presence of six inflammatory proteins in EVs (FGF-21, HGF, IL-12B, PD-L1, PRDX3, and STAMBP) were significantly associated with frailty. EV inflammatory proteins were significantly altered by frailty status, race, sex, and poverty status. Notably, frail White participants had higher levels of EV-associated CD5, CD8A, CD244, CXCL1, CXCL6, CXCL11, LAP-TGF-beta-1 and MCP-4 compared to frail and non-frail African American participants. Frail White participants living below poverty had higher levels of EV-associated uPA. EV-associated CCL28 levels were highest in non-frail women and CXCL1 were highest in non-frail men. Men living below poverty had higher levels of CD5, CD8A, CXCL1, LAP-TGF-beta-1, and uPA. CXCL6 levels were significantly higher in individuals living above poverty. There was a significant correlation between EV mtDNA levels and the presence of inflammatory proteins.

Conclusions

These data suggest that mtDNA within EVs may act as a DAMP molecule in frailty. Its association with chemokines and other inflammatory EV cargo proteins, may contribute to the frailty phenotype. In addition, the social determinant of health, poverty, influences the inflammatory cargo of EVs in midlife.
A novel weevil-transmitted tymovirus found in mixed infection on hollyhock
Authors: Mahillon Mathieu , Brodard Justine , Kellenberger Isabelle , Blouin Arnaud G. , Schumpp Olivier
Published: January 2023

Leaves of hollyhock (Alcea rosea) exhibiting vein chlorosis and yellow mosaic symptoms were collected at public sites in Lausanne and Nyon, two cities of western Switzerland. Diagnostic methods untangled in samples from both sites the mixed infections of a novel isometric virus, tentatively named “Alcea yellow mosaic virus” (AYMV) with the carlavirus Gaillardia latent virus. A new potyvirus was also identified in samples from Nyon. A combination of Illumina, Nanopore and Sanger sequencing was necessary to assemble the full-length genome of AYMV, revealing an exceptionally high cytidine content and other features typically associated with members of the genus Tymovirus. The host range of AYMV was found to be restricted to mallows, including ornamentals as well as economically important plants. Phylogenetic analyses further showed that AYMV belongs to a Tymovirus subclade that also gathers the other mallow-infecting members. The virus was readily transmitted by sap inoculation, and the weevil species Aspidapion radiolus was evidenced as a vector. Transmission assays using another weevil or other insect species did not succeed, and seed transmission was not observed.
A review of diffusion-weighted magnetic resonance imaging in head and neck cancer patients for treatment evaluation and prediction of radiation-induced xerostomia
Authors: Ermongkonchai Tai , Khor Richard , Wada Morikatsu , Lau Eddie , Xing Daniel Tao , Ng Sweet Ping
Published: January 2023

The incidence of head and neck cancers (HNC) is rising worldwide especially with HPV-related oropharynx squamous cell carcinoma. The standard of care for the majority of patients with locally advanced pharyngeal disease is curative-intent radiotherapy (RT) with or without concurrent chemotherapy. RT-related toxicities remain a concern due to the close proximity of critical structures to the tumour, with xerostomia inflicting the most quality-of-life burden. Thus, there is a paradigm shift towards research exploring the use of imaging biomarkers in predicting treatment outcomes. Diffusion-weighted imaging (DWI) is a functional MRI feature of interest, as it quantifies cellular changes through computation of apparent diffusion coefficient (ADC) values. DWI has been used in differentiating HNC lesions from benign tissues, and ADC analyses can be done to evaluate tumour responses to RT. It is also useful in healthy tissues to identify the heterogeneity and physiological changes of salivary glands to better understand the inter-individual differences in xerostomia severity. Additionally, DWI is utilised in irradiated salivary glands to produce ADC changes that correlate to clinical xerostomia. The implementation of DWI into multi-modal imaging can help form prognostic models that identify patients at risk of severe xerostomia, and thus guide timely interventions to mitigate these toxicities.
Inhibiting KCNMA1-AS1 promotes osteogenic differentiation of HBMSCs via miR-1303/cochlin axis
Authors: Lin Yuan , Dai Hanhao , Yu Guoyu , Song Chao , Liu Jun , Xu Jie
Published: January 2023

Objective

Osteoporosis is a progressive systemic skeletal disorder. Multiple profiling studies have contributed to characterizing biomarkers and therapeutic targets for osteoporosis. However, due to the limitation of the platform of miRNA sequencing, only a part of miRNA can be sequenced based on one platform.

Materials and methods

In this study, we performed miRNA sequencing in osteoporosis bone samples based on a novel platform Illumina Hiseq 2500. Bioinformatics analysis was performed to construct osteoporosis-related competing endogenous RNA (ceRNA) networks. Gene interference and osteogenic induction were used to examine the effect of identified ceRNA networks on osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (HBMSCs).

Results

miR-1303 was lowly expressed, while cochlin (COCH) and KCNMA1-AS1 were highly expressed in the osteoporosis subjects. COCH knockdown improved the osteogenic differentiation of HBMSCs. Meanwhile, COCH inhibition compensated for the suppression of osteogenic differentiation of HBMSCs by miR-1303 knockdown. Further, KCNMA1-AS1 knockdown promoted osteogenic differentiation of HBMSCs through downregulating COCH by sponging miR-1303.

Conclusions

Our findings suggest that the KCNMA1-AS1/miR-1303/COCH axis is a promising biomarker and therapeutic target for osteoporosis.
Novel nomograms for predicting the risk of low distal bone strength: development and validation in a Chinese population-based observational study
Authors: Wu Congzi , Liu Ting , Shi Zhenyu , Fang Liang , Jin Hongting , Tong Peijian
Published: January 2023

Background

This study aims to develop nomogram models based on the speed of sound (SOS) measurements results along with demographic information to predict the risk of low bone strength (LBS) of radius appropriate to the Chinese population of a broad age spectrum.

Methods

A population-based cross-sectional study was conducted in 5 outpatient clinics located in Zhejiang, the southern part of China. A total of 38,699 participants from 2013 to 2017 were included. Baseline measurements included SOS of the distal radius and clinical risk factor evaluation. Logistic regression models were used to evaluate prognosis and identify independent predictive factors, which were then utilized to establish nomograms for predicting the low bone strength of radius. The discrimination and calibration of nomograms were validated using the calibration plots, the decision curve analysis (DCA), and the receiver operating characteristics curve (ROC).

Results

A total of 19,845 of the 38,904 participants ranged in age from 10 to 88 years were selected in this process. LBP nomogram model 1 was constructed based on age, weight, height, BMI, and gender. LBP nomogram model 2 was constructed based on age, height, BMI, and gender. The AUCs for model 1 and model 2 were 0.838 (95% CI: 0.832–0.844) and 0.837 (95% CI: 0.831–0.843), respectively. High-quality calibration plots and DCA in nomogram models were noticed, indicated that the constructed nomogram models were clinically useful.

Conclusions

Our study demonstrates that the nomograms established in this study could effectively evaluate the high-risk population groups of distal radius fracture in China.
What we don't need to prove but need to do in multidisciplinary treatment and care in Huntington's disease: a position paper
Authors: Mühlbӓck Alzbeta , van Walsem Marleen , Nance Martha , Arnesen Astri , Page Kirsty , Fisher Alexandra , van Kampen Manon , Nuzzi Angela , Limpert Roy , Fossmo Hanne Ludt , Cruickshank Travis , Veenhuizen Ruth ,   the Multidisciplinary Care and Treatment Working Group of the European Huntington’s Disease Network
Published: January 2023

Background

Huntington’s disease is a complex neurodegenerative hereditary disease with symptoms in all domains of a person’s functioning. It begins after a healthy start in life and leads through the relentless progression over many years to complete care dependency and finally death. To date, the disease is incurable. The long progressive complex nature of the disease demands multiple disciplines for treatment and care of patient and family. These health care providers need inter- and multidisciplinary collaboration to persevere and be efficacious in this devastating disease trajectory.

Discussion

The position paper outlines current knowledge and experience alongside the experience and consensus of a recognised group of HD multidisciplinary experts. Additionally the patient’s voice is clear and calls for health care providers with a holistic view on patient and family. Building long-term trust is a cornerstone of the network around the patient. This paper describes a managed care network comprising all the needed professionals and services. In the health care system, the role of a central coordinator or case manager is of key importance but lacks an appropriate guideline. Other disciplines currently without guidelines are general practitioners, nurses, psychologists, and social workers. Guidelines for neurologists, psychiatrists, geneticists, occupational therapists, speech and language therapists, physiotherapists, dieticians, and dentists are being discussed. Apart from all these profession-specific guidelines, distinctive inter- and multidisciplinary collaboration requirements must be met.

Conclusions and recommendations

The complex nature of Huntington's disease demands multidisciplinary treatment and care endorsed by international regulations and the lay association. Available guidelines as reviewed in this paper should be used, made available by a central body, and updated every 3–5 years. Time needs to be invested in developing missing guidelines but the lack of this ‘proof’ should not prevent the ‘doing’ of good care.