bluuebunny/crossref_metadata_2025 huggingface dataset:
The safety of remimazolam versus propofol in gastroscopic sedation: a meta-analysis
Authors: An Xincan , Shen Tianqi , Yin Xingxing , Xu Jin , Zhang Yongming , Wang Tianlong
Published: January 2024

Background

This meta-analysis was designed to compare the safety and efficiency of remimazolam with those of propofol in patients undergoing gastroscope sedation.

Methods

We searched PubMed, Cochrane Library, Embase, Ovid, Wanfang Database, China National Knowledge Infrastructure, SINOMED, and ClinicalTrials.gov for studies that reported on remimazolam versus propofol for gastroscope sedation from establishment to February 25, 2023. The sedative efficiency and the incidence of adverse events were assessed as outcomes. Version 2 of the Cochrane risk-of-bias assessment tool was used to assess the risk of bias. Review Manager 5.4 and STATA 17 were used to perform all statistical analyses.

Results

A total of 26 randomized controlled trials involving 3,641 patients were included in this meta-analysis. The results showed that remimazolam had a significantly lower incidence of respiratory depression (risk ratio [RR] = 0.40, 95% confidence interval [CI]: 0.28–0.57; p < 0.01, GRADE high), hypoxemia (RR = 0.34, 95% CI: 0.23–0.49; p < 0.01, GRADE high), bradycardia (RR = 0.34, 95% CI: 0.23–0.51; p < 0.01, GRADE high), dizziness (RR = 0.45, 95% CI: 0.31–0.65; p < 0.01, GRADE high), injection site pain (RR = 0.06, 95% CI: 0.03–0.13; p < 0.01, GRADE high), nausea or vomiting (RR = 0.79, 95% CI: 0.62–1.00; p = 0.05, GRADE moderate), and hypotension (RR = 0.36, 95% CI: 0.26–0.48; p < 0.01, GRADE low).

Conclusions

Remimazolam can be used safely in gastroscopic sedation and reduces the incidence of respiratory depression, hypoxemia, bradycardia, injection site pain, and dizziness compared with propofol, and doesn't increase the incidence of nausea and vomiting.
The two therapeutic strategies of surgical intervention and medical management in a patient with enhanced-fibrinolytic type of disseminated intravascular coagulation after aortic replacement for Stanford type A aortic dissection with chronic heart and renal failure
Authors: Okamoto Hiroki , Ozawa Tomoya , Suzuki Tomoaki , Nakagawa Yoshihisa
Published: January 2024

Background

Management of the enhanced-fibrinolytic type of disseminated intravascular coagulation (DIC) caused by aortic disorders is the two strategies of surgical intervention and medical treatment based on the patient’s age and comorbidities.

Case presentation

An 81-year-old woman with a history of two previous aortic surgeries and chronic heart and renal failure was admitted for uncontrollable subcutaneous hemorrhage. The hemorrhage was caused by the enhanced-fibrinolytic type of disseminated intravascular coagulation (DIC) caused by periprosthetic graft hematoma after aortic replacement for Stanford type A aortic dissection. Open thoracic hemostasis temporarily controlled the subcutaneous hemorrhage, but she was readmitted for the recurrence seven months after discharge. On the second admission, the combination of anticoagulant and antifibrinolytic agents was successful.

Conclusion

Management of the enhanced-fibrinolytic type of DIC caused by aortic disorders is important of a successful combination of surgical and medical therapy tailored the patient’s condition.
Prevalence of physical inactivity and associated factors among older adults in Gondar town, Northwest Ethiopia: a community-based cross-sectional study
Authors: Shiferaw Kassaw Belay , Yalew Ermias Solomon , Zemed Ashenafi , Yitayal Melisew Mekie , Belay Gashaw Jember , Alie Melkamu , Kibret Alemu Kassaw , Takele Mihret Dejen , Abich Yohannes , Gashaw Moges
Published: January 2024

Introduction

Older adults are increasing in number in both developed and developing countries. However, as the world’s aging population grows, the burden of diseases among older people also increases. Despite this, co-occurring health problems due to physical inactivity in older adults have become a concern, and physical inactivity can be caused by different conditions. As a result, for older adults to have better health outcomes, early diagnosis of physical activity status and prevention of non-communicable diseases are crucial. There is a lack of data on the prevalence and associated factors of physical inactivity among older adults that is scarce in sub-Saharan Africa, particularly in the study area, Ethiopia. Therefore, this study aimed to assess the prevalence and associated factors of physical inactivity among older adults in Gondar town, Northwest Ethiopia, in 2022.

Methods

A community-based cross-sectional study was conducted from April 1st to June 30th, 2022, in Gondar town, Northwest Ethiopia. The data was collected by the Global Physical Activity Questionnaire, Volume 2 through face-to-face interviews among 838 participants. Data were entered into Epinfo version 7.1, then exported and analysed using the Statistical Package of Social Science version 25. A binary logistic regression model was performed to identify factors associated with physical inactivity. The result was considered statistically significant based on an adjusted odds ratio of 95% and a p-value less than 0.05.

Result

The prevalence of physical inactivity was 65.6% (95% CI: 62.1–68.9). Being female (AOR: 3.053, 95% CI:1.487–6.267), age group > = 80 (AOR: 4.082, 95% CI:1.234–13.497), primary school level (AOR: 3.020, 95% CI:1.433–6.367), no formal education (AOR: 8.573, 95% CI:2.843–25.847), unemployed (AOR: 10.273, 95% CI:5.628–18.753), and symptoms of depression (AOR: 7.152, 95% CI: 4.786–17.965) were significantly associated with physical inactivity.

Conclusion

Physical inactivity was relatively high among older adults in Gondar town. Being female, older age, having low levels of education, being unemployed, and having depression symptoms were associated with physical inactivity. We suggest promoting the health benefits of physical activity among females by reducing their burden, older age groups, and unemployed older adults, and avoiding depression among individuals.
Impact of closed-off management due to COVID-19 rebound on maternal depression during pregnancy
Authors: Xiao Wanqing , Yang Yuting , Xiao Huiyun , Huang Peiyuan , Wei Dongmei , Wu Yingfang , Yu Jia , He Jian-Rong , Qiu Xiu
Published: January 2024

Background

This study aimed to assess the impacts of closed-off measures with different strictness levels (lockdown, partial lockdown and non-lockdown) and geographic proximity to patients with coronavirus disease 2019 (COVID-19) on prenatal depression during an epidemic rebound of COVID-19.

Methods

This was a cross-sectional web-based survey including 880 pregnant women. Depressive symptoms were measured by Self-Rating Depression Scale (SDS) and geographic proximity was calculated using Geographic Information Systems. Linear and logistic regression were used to assess the associations of closed-off measures and geographic proximity with SDS scores and depressive symptoms. Restricted cubic splines were used to model non-linear associations between geographic proximity and depression symptoms.

Results

Compared with those living in non-lockdown areas, women in lockdown areas had higher SDS scores (adjusted β: 3.51, 95% CI: 1.80, 5.21) and greater risk of depressive symptoms (adjusted OR: 4.00, 95% CI: 2.18, 7.35), but evidence for partial lockdown was not obvious. A progressive increase in the risk of depressive symptoms was found with decreasing distance to COVID-19 patients when geographic proximity was <8 kilometers. Compared to those in the 5th quintile of geographic proximity, women in the first, second and third quintiles had at least 6 times higher risk of depressive symptoms.

Conclusions

Pregnant women under strict closed-off management during COVID-19 epidemic have high risk of depression. A specific range around the residences of reported COVID-19 patients should be underlined as potential clustering of high prenatal depression levels. Our findings highlight the importance of enhancing mental health management during the COVID-19 epidemic for pregnant women.
A follow-up study on factors affecting the recovery of patients with hypothyroidism in different selenium environments
Authors: Wang Si , Chen Ping , He Yayi , Wei Jing , Tian Li , Wu Yajun , Lv Hongjun , Peng Xiaogang , Zhang Xingru , Shi Bingyin , Wu Qian
Published: January 2024

Background

Hypothyroidism is a major manifestation of autoimmune thyroid diseases (AITD). We previously reported that a low selenium (Se) status was linked to an elevated prevalence of thyroid diseases. We hypothesized that Se status may also influence the restoration of thyroid function. Thus, this study aimed to investigate the factors affecting the recovery of thyroid function in patients with (sub-)clinical hypothyroidism, with a specific focus on Se status.

Methods

We conducted a 6-year prospective cohort study comparing two counties with different Se concentrations. Demographic and disease data were collected from 1,190 individuals (549 Se-adequate and 641 Se-deficient) who completed a follow-up study in 2019. In addition, urinary iodine (I) levels, thyroid function, and serum and nail Se levels were measured. Logistic regression was used to investigate the relationship between Se deficiency and recovery of thyroid function.

Results

Sex and smoking status was similar between the two counties studied. Thyroid function recovery rate was significantly higher in Se-deficient counties (46.0% vs. 30.6%, P = 0.008). In the multivariate analysis, our results show that female sex (odds ratio [OR] (95% confidence interval [CI]) = 1.875 (1.080–3.257), P = 0.026] and increasing age [OR (95%CI) = 1.028(1.007–1.049), P = 0.009] were associated with the recovery rate. Additionally, our study revealed that while Se status was significant in the univariate analysis, this association appeared to disappear in the multivariate analysis.

Conclusions

Female sex and increasing age have unfavorable effects on the recovery of thyroid function in patients over 30 years of age with (sub-) clinical hypothyroidism.
Electro-acupuncture for central obesity: a patient-assessor blinded, randomized sham-controlled clinical trial
Authors: Lam Tsz Fung , Lyu Zipan , Wu Xingyao , Wong Yi Ping , Cao Peihua , Wong Emily Yen , Hung Hung Bun , Zhang Shiping , Bian Zhaoxiang , Zhong Linda L. D.
Published: January 2024

Background

Central obesity is considered as a significant health threat to individuals. Scientific research has demonstrated that intra-abdominal fat accumulation is associated with higher metabolic and cardiovascular disease risks independent of Body Mass Index (BMI). This study aimed to evaluate the efficacy and safety of electro-acupuncture in treating central obesity compared with sham acupuncture.

Method

This was a patient-assessor blinded, randomized, sham-controlled clinical trial. One hundred sixty eight participants aged between 18 and 65 years old with BMI ≥ 25 kg/m2 and waist circumference (WC) of men ≥ 90 cm / women ≥ 80 cm were enrolled and allocated to the acupuncture or sham acupuncture group equally. For the acupuncture group, disposable acupuncture needles were inserted into eight body acupoints, including Tianshu (ST-25), Daheng (SP-15), Daimai (GB-26), Qihai (CV-6), Zhongwan (CV-12), Zusanli (ST-36), Fenglong (ST-40), and Sanyinjiao (SP-6) with electrical stimulation. For the control group, Streitberger’s non-invasive acupuncture needles were utilized at the same acupoints with identical stimulation modalities. The treatment duration was 8 weeks with 2 sessions per week and the follow-up period was 8 weeks. The primary outcome was the change in WC before and after the treatment. The secondary outcomes were the changes in hip circumference, waist-to-hip circumference ratio, BMI, and body fat percentage during the treatment and follow-up period.

Results

The acupuncture group displayed a significant change in WC compared to the sham group both treatment and follow-up period (MD = -1.1 cm, 95% CI = -2.8 to 4.1). Significant change in body fat percentage was recorded for both groups after treatment but no significance was observed during the follow-up period (MD = -0.1%, 95% CI = -1.9 to 2.2). The changes in hip circumference were also significant both treatment and follow-up period for the acupuncture group (MD = -2.0 cm, 95% CI = -3.7 to -1.7). Compared with sham acupuncture, the body weight (MD = -1 kg, 95% CI = -3.3 to 5.3), BMI (MD = -0.5, 95% CI = -0.7 to 1.9) also decreased significantly within and between groups. The incidence of adverse events was similar in the two groups.

Conclusion

This study provided evidence that electro-acupuncture could be effective in treating central obesity by reducing WC, hip circumference, body weight, BMI, and waist-to-hip circumference ratio.

Trial registration

ClinicalTrials.gov Identifier: NCT03815253, Registered 24 Jan 2019.
A computational model of circRNA-associated diseases based on a graph neural network: prediction and case studies for follow-up experimental validation
Authors: Niu Mengting , Wang Chunyu , Zhang Zhanguo , Zou Quan
Published: January 2024

Background

Circular RNAs (circRNAs) have been confirmed to play a vital role in the occurrence and development of diseases. Exploring the relationship between circRNAs and diseases is of far-reaching significance for studying etiopathogenesis and treating diseases. To this end, based on the graph Markov neural network algorithm (GMNN) constructed in our previous work GMNN2CD, we further considered the multisource biological data that affects the association between circRNA and disease and developed an updated web server CircDA and based on the human hepatocellular carcinoma (HCC) tissue data to verify the prediction results of CircDA.

Results

CircDA is built on a Tumarkov-based deep learning framework. The algorithm regards biomolecules as nodes and the interactions between molecules as edges, reasonably abstracts multiomics data, and models them as a heterogeneous biomolecular association network, which can reflect the complex relationship between different biomolecules. Case studies using literature data from HCC, cervical, and gastric cancers demonstrate that the CircDA predictor can identify missing associations between known circRNAs and diseases, and using the quantitative real-time PCR (RT-qPCR) experiment of HCC in human tissue samples, it was found that five circRNAs were significantly differentially expressed, which proved that CircDA can predict diseases related to new circRNAs.

Conclusions

This efficient computational prediction and case analysis with sufficient feedback allows us to identify circRNA-associated diseases and disease-associated circRNAs. Our work provides a method to predict circRNA-associated diseases and can provide guidance for the association of diseases with certain circRNAs. For ease of use, an online prediction server (http://server.malab.cn/CircDA) is provided, and the code is open-sourced (https://github.com/nmt315320/CircDA.git) for the convenience of algorithm improvement.
Fabrication of magnetic niosomal platform for delivery of resveratrol: potential anticancer activity against human pancreatic cancer Capan-1 cell
Authors: Firouzi Amandi Akram , Bahmanyar Zahra , Dadashpour Mehdi , Lak Mehrnoosh , Natami Mohammad , Döğüş Yusuf , Alem Mahsa , Adeli Omid Ali
Published: January 2024

Recently, the presence of different nanoparticles (NPs) has developed targeting drug delivery in treatment of cancer cell. Targeted drug delivery systems using NPs have shown great promise in improving the efficacy of intracellular uptake as well as local concentration of therapeutics with minimizing side effects. The current study planned to synthesized resveratrol-loaded magnetic niosomes nanoparticles (RSV-MNIONPs) and evaluate their cytotoxicity activity in pancreatic cancer cells. For this aim, magnetic nanoparticles (MNPs) were synthesized and loaded into niosomes (NIOs) by the thin film hydration technique and then characterized via DLS, FT-IR, TEM, SEM and VSM techniques. Moreover, the cytotoxic activity of the RSV-MNIONPs on the Capan-1 cells line was assessed by the MTT test. The distribution number of RSV-MNIONPs was gained about 80 nm and 95 nm with surface charge of − 14.0 mV by SEM and TEM analysis, respectively. RSV loading efficacy in NIOs was about 85%, and the drug releases pattern displayed a sustained discharge with a maximum amount about 35% and 40%, within 4 h in pH = 7.4 and pH = 5.8, respectively. The cytotoxicity of the RSV-MNIONPs in the presence of an external magnetic field is higher than that of the RSV, indicating enhanced cellular uptake in their encapsulated states. Furthermore, RSV loaded MNNPs were found to induce more cell cycle arrest at the G0/G1 checkpoint than free RSV. Compared with RSV-treated cells, the mRNA expression levels of BAX, Bcl2, FAS, P 53, Cyclin D and hTERT, were significantly changed in cells treated with RSV loaded MNNPs. The niosomes NPs approaches have been widely used to attain higher solubility, improved bioavailability, enhanced stability, and control delivery of RSV. Our formulation displayed antitumor activity and can be considered an appropriate carrier with a great potential for future usage in cancer therapy.
Using alone at home: What’s missing in housing-based responses to the overdose crisis?
Authors: Fleming Taylor , Boyd Jade , Chayama Koharu Loulou , Knight Kelly R. , McNeil Ryan
Published: January 2024

Background

Against the backdrop of North America’s overdose crisis, most overdose deaths are occurring in housing environments, largely due to individuals using drugs alone. Overdose deaths in cities remain concentrated in marginal housing environments (e.g., single-room occupancy housing, shelters), which are often the only forms of housing available to urban poor and drug-using communities. This commentary aims to highlight current housing-based overdose prevention interventions and to situate them within the broader environmental contexts of marginal housing. In doing so, we call attention to the need to better understand marginal housing as sites of overdose vulnerability and public health intervention to optimize responses to the overdose crisis.

Harm reduction and overdose prevention in housing

In response to high overdose rates in marginal housing environments several interventions (e.g., housing-based supervised consumption rooms, peer-witnessed injection) have recently been implemented in select jurisdictions. However, even with the growing recognition of marginal housing as a key intervention site, housing-based interventions have yet to be scaled up in a meaningful way. Further, there have been persistent challenges to tailoring these approaches to address dynamics within housing environments. Thus, while it is critical to expand coverage of housing-based interventions across marginal housing environments, these interventions must also attend to the contextual drivers of risks in these settings to best foster enabling environments for harm reduction and maximize impacts.

Conclusion

Emerging housing-focused interventions are designed to address key drivers of overdose risk (e.g., using alone, toxic drug supply). Yet, broader contextual factors (e.g., drug criminalization, housing quality, gender) are equally critical factors that shape how structurally vulnerable people who use drugs navigate and engage with harm reduction interventions. A more comprehensive understanding of these contextual factors within housing environments is needed to inform policy and programmatic interventions that are responsive to the needs of people who use drugs in these settings.
Dopamine modification of glycolytic enzymes impairs glycolysis: possible implications for Parkinson’s disease
Authors: Chen Bing , Zhang Qian , Zhong Xiaoru , Zhang Xinwei , Liu Xin , Wang Hongyang , Yang Fan , Zhang Jingjing , Huang Jingnan , Wong Yin-Kwan , Luo Piao , Wang Jigang , Sun Jichao
Published: January 2024

Background

Parkinson’s disease (PD), a chronic and severe neurodegenerative disease, is pathologically characterized by the selective loss of nigrostriatal dopaminergic neurons. Dopamine (DA), the neurotransmitter produced by dopaminergic neurons, and its metabolites can covalently modify proteins, and dysregulation of this process has been implicated in neuronal loss in PD. However, much remains unknown about the protein targets.

Methods

In the present work, we designed and synthesized a dopamine probe (DA-P) to screen and identify the potential protein targets of DA using activity-based protein profiling (ABPP) technology in combination with liquid chromatography-tandem mass spectrometry (LC–MS/MS). In situ pull-down assays, cellular thermal shift assays (CETSAs) and immunofluorescence were performed to confirm the DA modifications on these hits. To investigate the effects of DA modifications, we measured the enzymatic activities of these target proteins, evaluated glycolytic stress and mitochondrial respiration by Seahorse tests, and systematically analyzed the changes in metabolites with unbiased LC–MS/MS-based non-targeted metabolomics profiling.

Results

We successfully identified three glycolytic proteins, aldolase A, α-enolase and pyruvate kinase M2 (PKM2), as the binding partners of DA. DA bound to Glu166 of α-enolase, Cys49 and Cys424 of PKM2, and Lys230 of aldolase A, inhibiting the enzymatic activities of α-enolase and PKM2 and thereby impairing ATP synthesis, resulting in mitochondrial dysfunction.

Conclusions

Recent research has revealed that enhancing glycolysis can offer protection against PD. The present study identified that the glycolytic pathway is vulnerable to disruption by DA, suggesting a promising avenue for potential therapeutic interventions. Safeguarding glycolysis against DA-related disruption could be a potential therapeutic intervention for PD.
Exploration of a hypoxia-immune-related microenvironment gene signature and prediction model for hepatitis C-induced early-stage fibrosis
Authors: Chen Chuwen , Cai Haozheng , Shen Junyi , Zhang Xiaoyun , Peng Wei , Li Chuan , Lv Haopeng , Wen Tianfu
Published: January 2024

Background

Liver fibrosis contributes to significant morbidity and mortality in Western nations, primarily attributed to chronic hepatitis C virus (HCV) infection. Hypoxia and immune status have been reported to be significantly correlated with the progression of liver fibrosis. The current research aimed to investigate the gene signature related to the hypoxia-immune-related microenvironment and identify potential targets for liver fibrosis.

Method

Sequencing data obtained from GEO were employed to assess the hypoxia and immune status of the discovery set utilizing UMAP and ESTIMATE methods. The prognostic genes were screened utilizing the LASSO model. The infiltration level of 22 types of immune cells was quantified utilizing CIBERSORT, and a prognosis-predictive model was established based on the selected genes. The model was also verified using qRT-PCR with surgical resection samples and liver failure samples RNA-sequencing data.

Results

Elevated hypoxia and immune status were linked to an unfavorable prognosis in HCV-induced early-stage liver fibrosis. Increased plasma and resting NK cell infiltration were identified as a risk factor for liver fibrosis progression. Additionally, CYP1A2, CBS, GSTZ1, FOXA1, WDR72 and UHMK1 were determined as hypoxia-immune-related protective genes. The combined model effectively predicted patient prognosis. Furthermore, the preliminary validation of clinical samples supported most of the conclusions drawn from this study.

Conclusion

The prognosis-predictive model developed using six hypoxia-immune-related genes effectively predicts the prognosis and progression of liver fibrosis. The current study opens new avenues for the future prediction and treatment of liver fibrosis.
m6A methylation-mediated regulation of LncRNA MEG3 suppresses ovarian cancer progression through miR-885-5p and the VASH1 pathway
Authors: Li Yan , Lou Shenghan , Zhang Jian , Zhao Shilu , Lou Ge
Published: January 2024

Background

Ovarian cancer poses a serious threat to women's health. Due to the difficulty of early detection, most patients are diagnosed with advanced-stage disease or peritoneal metastasis. We found that LncRNA MEG3 is a novel tumor suppressor, but its role in tumor occurrence and development is still unclear.

Methods

We investigated the expression level of MEG3 in pan-cancer through bioinformatics analysis, especially in gynecological tumors. Function assays were used to detect the effect of MEG3 on the malignant phenotype of ovarian cancer. RIP, RNA pull-down, MeRIP-qPCR, actinomycin D test were carried out to explore the m6A methylation-mediated regulation on MEG3. Luciferase reporter gene assay, PCR and Western blot were implemented to reveal the potential mechanism of MEG3. We further confirmed the influence of MEG3 on tumor growth in vivo by orthotopic xenograft models and IHC assay.

Results

In this study, we discovered that MEG3 was downregulated in various cancers, with the most apparent downregulation in ovarian cancer. MEG3 inhibited the proliferation, migration, and invasion of ovarian cancer cells. Overexpression of MEG3 suppressed the degradation of VASH1 by negatively regulating miR-885-5p, inhibiting the ovarian cancer malignant phenotype. Furthermore, we demonstrated that MEG3 was regulated at the posttranscriptional level. YTHDF2 facilitated MEG3 decay by recognizing METTL3‑mediated m6A modification. Compared with those injected with vector control cells, mice injected with MEG3 knockdown cells showed larger tumor volumes and faster growth rates.

Conclusion

We demonstrated that MEG3 is influenced by METTL3/YTHDF2 methylation and restrains ovarian cancer proliferation and metastasis by binding miR-885-5p to increase VASH1 expression. MEG3 is expected to become a therapeutic target for ovarian cancer.
Fall risk classification with posturographic parameters in community-dwelling older adults: a machine learning and explainable artificial intelligence approach
Authors: Liang Huey-Wen , Ameri Rasoul , Band Shahab , Chen Hsin-Shui , Ho Sung-Yu , Zaidan Bilal , Chang Kai-Chieh , Chang Arthur
Published: January 2024

Background

Computerized posturography obtained in standing conditions has been applied to classify fall risk for older adults or disease groups. Combining machine learning (ML) approaches is superior to traditional regression analysis for its ability to handle complex data regarding its characteristics of being high-dimensional, non-linear, and highly correlated. The study goal was to use ML algorithms to classify fall risks in community-dwelling older adults with the aid of an explainable artificial intelligence (XAI) approach to increase interpretability.

Methods

A total of 215 participants were included for analysis. The input information included personal metrics and posturographic parameters obtained from a tracker-based posturography of four standing postures. Two classification criteria were used: with a previous history of falls and the timed-up-and-go (TUG) test. We used three meta-heuristic methods for feature selection to handle the large numbers of parameters and improve efficacy, and the SHapley Additive exPlanations (SHAP) method was used to display the weights of the selected features on the model.

Results

The results showed that posturographic parameters could classify the participants with TUG scores higher or lower than 10 s but were less effective in classifying fall risk according to previous fall history. Feature selections improved the accuracy with the TUG as the classification label, and the Slime Mould Algorithm had the best performance (accuracy: 0.72 to 0.77, area under the curve: 0.80 to 0.90). In contrast, feature selection did not improve the model performance significantly with the previous fall history as a classification label. The SHAP values also helped to display the importance of different features in the model.

Conclusion

Posturographic parameters in standing can be used to classify fall risks with high accuracy based on the TUG scores in community-dwelling older adults. Using feature selection improves the model’s performance. The results highlight the potential utility of ML algorithms and XAI to provide guidance for developing more robust and accurate fall classification models.

Trial registration Not applicable
Models and approaches for building knowledge translation capacity and capability in health services: a scoping review
Authors: King Olivia , West Emma , Alston Laura , Beks Hannah , Callisaya Michele , Huggins Catherine E. , Murray Margaret , Mc Namara Kevin , Pang Michael , Payne Warren , Peeters Anna , Pithie Mia , Sayner Alesha M. , Wong Shee Anna
Published: January 2024

Background

Building healthcare service and health professionals’ capacity and capability to rapidly translate research evidence into health practice is critical to the effectiveness and sustainability of healthcare systems. This review scoped the literature describing programmes to build knowledge translation capacity and capability in health professionals and healthcare services, and the evidence supporting these.

Methods

This scoping review was undertaken using the Joanna Briggs Institute scoping review methodology. Four research databases (Ovid MEDLINE, CINAHL, Embase, and PsycInfo) were searched using a pre-determined strategy. Eligible studies described a programme implemented in healthcare settings to build health professional or healthcare service knowledge translation capacity and capability. Abstracts and full texts considered for inclusion were screened by two researchers. Data from included papers were extracted using a bespoke tool informed by the scoping review questions.

Results

Database searches yielded 10,509 unique citations, of which 136 full texts were reviewed. Thirty-four papers were included, with three additional papers identified on citation searching, resulting in 37 papers describing 34 knowledge translation capability building programmes.

Programmes were often multifaceted, comprising a combination of two or more strategies including education, dedicated implementation support roles, strategic research-practice partnerships and collaborations, co-designed knowledge translation capability building programmes, and dedicated funding for knowledge translation. Many programmes utilised experiential and collaborative learning, and targeted either individual, team, organisational, or system levels of impact. Twenty-seven programmes were evaluated formally using one or more data collection methods. Outcomes measured varied significantly and included participant self-reported outcomes, perceived barriers and enablers of knowledge translation, milestone achievement and behaviour change. All papers reported that programme objectives were achieved to varying degrees.

Conclusions

Knowledge translation capacity and capability building programmes in healthcare settings are multifaceted, often include education to facilitate experiential and collaborative learning, and target individual, team, organisational, or supra-organisational levels of impact. Although measured differently across the programmes, the outcomes were positive. The sustainability of programmes and outcomes may be undermined by the lack of long-term funding and inconsistent evaluation. Future research is required to develop evidence-informed frameworks to guide methods and outcome measures for short-, medium- and longer-term programme evaluation at the different structural levels.
Gastric and cardiac inflammatory myofibroblastic tumor: an extremely rare case
Authors: Huang Yueqi , Zhang Mingqi , Li Qingchun , Huang Qiulin
Published: January 2024

Background

Inflammatory myofibroblastic tumor (IMT) is a unique, rarely metastatic tumor composed of myofibroblasts and fibrous spindle cells with inflammatory cell infiltration that can affect any organ in the human body. By reviewing the relevant literature on PubMed, we found that this is the first case report of IMT with both gastric and cardiac involvement.

Case presentation

A 57-year-old male patient was admitted to the hospital with complaints of malaise, poor appetite, and epigastric pain with black stools. We found a mass in the patient’s stomach and left atrium by contrast-enhanced computed tomography, 18 F-fluorodeoxyglucose positron emission tomography/computed tomography, and other tests. The patient underwent laparoscopic Billroth II subtotal gastrectomy and Braun’s gastrointestinal reconstruction under general anesthesia. On the 46th day following stomach surgery, the cardiac tumor was removed under general anesthesia. The patient has treated with doxorubicin 70 mg of D1 chemotherapy two months after cardiac surgery. Postoperative pathological immunohistochemistry of the mass confirmed the diagnosis of an IMT. His review three months after the cardiac surgery suggested the progression of the left atrial mass, but he declined further treatment and finally died one month after the review.

Conclusions

As a unique class of tumors that rarely metastasize, IMTs have an unknown etiology and pathogenesis, and distant metastasis is primarily observed in patients with negative activin receptor-like kinase (ALK) expression. The preferred treatment for IMT is complete surgical resection, and the effectiveness of adjuvant therapy for patients with distant metastases is still being determined. The clinical presentation of IMT lacks specificity and is often related to the location of tumor growth, which poses a diagnostic challenge. Pathological immunohistochemistry is the only way to confirm the diagnosis at present. Our case report reminds clinicians that a category of ALK-negative IMT with a tendency toward distant metastasis should not be ignored.
Exploring the association of ESR1 and ESR2 gene SNPs with polycystic ovary syndrome in human females: a comprehensive association study
Authors: Muccee Fatima , Ashraf Naeem Mahmood , Razak Suhail , Afsar Tayyaba , Hussain Nadia , Husain Fohad Mabood , Shafique Huma
Published: January 2024

Background

Polycystic Ovary Syndrome (PCOS) affects a significant proportion of human females worldwide and is characterized by hormonal, metabolic, and reproductive dysfunctions, including infertility, irregular menstrual cycles, acanthosis nigricans, and hirsutism. Mutations in the estrogen receptor genes ESR1 and ESR2, involved in normal follicular development and ovulation, can contribute to development of the PCOS. The present study focuses on investigating the potential correlation between single nucleotide polymorphisms (SNPs) of ESR1 and ESR2 genes and the incidence of this syndrome.

Methods

For this study, SNPs in ESR1 and ESR2 genes were retrieved from the ENSEMBL database and analyzed for their effect on mutated proteins using different bioinformatics tools including SIFT, PolyPhen, CADD, REVEL, MetaLR, I-Mutant, CELLO2GO, ProtParam, SOPMA, SWISS-MODEL and HDDOCK.

Results

All the SNPs documented in the present study were deleterious. All the SNPs except rs1583384537, rs1450198518, and rs78255744 decreased protein stability. Two variants rs1463893698 and rs766843910 in the ESR2 gene altered the localization of mutated proteins i.e. in addition to the nucleus, proteins were also found in mitochondria and extracellular, respectively. SNPs rs104893956 in ESR1 and rs140630557, rs140630557, rs1596423459, rs766843910, rs1596405923, rs762454979 and rs1384121511 in ESR2 gene significantly changed the secondary structure of proteins (2D). SNPs that markedly changed 3D configuration included rs1554259481, rs188957694 and rs755667747 in ESR1 gene and rs1463893698, rs140630557, rs1596423459, rs766843910, rs1596405923, rs762454979 and rs1384121511 in ESR2 gene. Variants rs1467954450 (ESR1) and rs140630557 (ESR2) were identified to reduce the binding tendency of ESRα and β receptors with estradiol as reflected by the docking scores i.e. -164.97 and -173.23, respectively.

Conclusion

Due to the significant impact on the encoded proteins, these variants might be proposed as biomarkers to predict the likelihood of developing PCOS in the future and for diagnostic purposes.
ADAMTS18 deficiency associates extracellular matrix dysfunction with a higher risk of HER2-positive mammary tumorigenesis and metastasis
Authors: Nie Jiahui , Dang Suying , Zhu Rui , Lu Tiantian , Zhang Wei
Published: January 2024

Background

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer accounts for about 20% of all breast cancer cases and is correlated with a high relapse rate and poor prognosis. ADAMTS18 is proposed as an important functional tumor suppressor gene involved in multiple malignancies, including breast cancer. It functions as an extracellular matrix (ECM) modifier. However, it remains unclear whether ADAMTS18 affects mammary tumorigenesis and malignant progression through its essential ECM regulatory function.

Methods

To elucidate the role of ADAMTS18 in HER2-positive mammary tumorigenesis and metastasis in vivo, we compared the incidence of mammary tumor and metastasis between Adamts18-knockout (MMTV)-Her2/ErbB2/Neu+ transgenic mice (i.e., Her2t/w/Adamts18−/−) and Adamts18-wildtype (MMTV)-Her2/ErbB2/Neu+ transgenic mice (i.e., Her2t/w/Adamts18+/+). The underlying mechanisms by which ADAMTS18 regulates HER2-positive tumorigenesis and metastasis were investigated by pathology, cell culture, Western blot and immunochemistry.

Results

Adamts18 mRNA is mainly expressed in myoepithelial cells of the mammary duct. ADAMTS18 deficiency leads to a significantly increased incidence of mammary tumors and metastasis, as well as mammary hyperplasia in mice, over 30 months of observation. The proliferation, migration and invasion capacities of primary Her2t/w/Adamts18−/− mammary tumor cells are significantly higher than those of primary Her2t/w/Adamts18+/+ mammary tumor cells in vitro. At 30 months of age, the expression levels of laminin (LNα5), fibronectin (FN) and type I collagen (ColI) in the mammary glands of Her2t/w/Adamts18−/− mice are significantly increased, and the activities of integrin-mediated PI3K/AKT, ERK and JNK signaling pathways are enhanced.

Conclusions

ADAMTS18 deficiency leads to alterations in mammary ECM components (e.g., LNα5, FN, ColI), which are associated with a higher risk of HER2-positive mammary tumorigenesis and metastasis.
Mosaic loss of Y chromosome is associated with aging and epithelial injury in chronic kidney disease
Authors: Wilson Parker C. , Verma Amit , Yoshimura Yasuhiro , Muto Yoshiharu , Li Haikuo , Malvin Nicole P. , Dixon Eryn E. , Humphreys Benjamin D.
Published: January 2024

Background

Mosaic loss of Y chromosome (LOY) is the most common chromosomal alteration in aging men. Here, we use single-cell RNA and ATAC sequencing to show that LOY is present in the kidney and increases with age and chronic kidney disease.

Results

The likelihood of a cell having LOY varies depending on its location in the nephron. Cortical epithelial cell types have a greater proportion of LOY than medullary or glomerular cell types, which may reflect their proliferative history. Proximal tubule cells are the most abundant cell type in the cortex and are susceptible to hypoxic injury. A subset of these cells acquires a pro-inflammatory transcription and chromatin accessibility profile associated with expression of HAVCR1, VCAM1, and PROM1. These injured epithelial cells have the greatest proportion of LOY and their presence predicts future kidney function decline. Moreover, proximal tubule cells with LOY are more likely to harbor additional large chromosomal gains and express pro-survival pathways. Spatial transcriptomics localizes injured proximal tubule cells to a pro-fibrotic microenvironment where they adopt a secretory phenotype and likely communicate with infiltrating immune cells.

Conclusions

We hypothesize that LOY is an indicator of increased DNA damage and potential marker of cellular senescence that can be applied to single-cell datasets in other tissues.
Impact of Menstrual cycle-based Periodized training on Aerobic performance, a Clinical Trial study protocol—the IMPACT study
Authors: Ekenros Linda , von Rosen Philip , Norrbom Jessica , Holmberg Hans-Christer , Sundberg Carl Johan , Fridén Cecilia , Hirschberg Angelica Lindén
Published: January 2024

Background

The menstrual cycle and its impact on training and performance are of growing interest. However, evidence is lacking whether periodized exercise based on the menstrual cycle is beneficial. The primary purpose of this proposed randomized, controlled trial, the IMPACT study, is to evaluate the effect of exercise periodization during different phases of the menstrual cycle, i.e., comparing follicular phase-based and luteal phase-based training with regular training during the menstrual cycle on physical performance in well-trained women.

Methods

Healthy, well-trained, eumenorrheic women between 18 and 35 years (n = 120) will be recruited and first assessed for physical performance during a run-in menstrual cycle at different cycle phases and then randomized to three different interventions: follicular phase-based training, luteal phase-based training, or regular training during three menstrual cycles. The training intervention will consist of high-intensity spinning classes followed by strength training. The menstrual cycle phases will be determined by serum hormone analysis throughout the intervention period. Assessment of aerobic performance (primary outcome) and muscle strength, body composition, and blood markers will be performed at baseline and at the end of the intervention.

Discussion

With a robust methodology, this study has the potential to provide evidence of the differential effects of exercise periodization during different phases of the menstrual cycle in female athletes.

Trial registration

ClinicalTrials.gov NCT05697263. Registered on 25 January 2023
Single-cell analysis of immune and stroma cell remodeling in clear cell renal cell carcinoma primary tumors and bone metastatic lesions
Authors: Mei Shenglin , Alchahin Adele M. , Tsea Ioanna , Kfoury Youmna , Hirz Taghreed , Jeffries Nathan Elias , Zhao Ting , Xu Yanxin , Zhang Hanyu , Sarkar Hirak , Wu Shulin , Subtelny Alexander O. , Johnsen John Inge , Zhang Yida , Salari Keyan , Wu Chin-Lee , Randolph Mark A. , Scadden David T. , Dahl Douglas M. , Shin John , Kharchenko Peter V. , Saylor Philip J. , Sykes David B. , Baryawno Ninib
Published: January 2024

Background

Despite therapeutic advances, once a cancer has metastasized to the bone, it represents a highly morbid and lethal disease. One third of patients with advanced clear cell renal cell carcinoma (ccRCC) present with bone metastasis at the time of diagnosis. However, the bone metastatic niche in humans, including the immune and stromal microenvironments, has not been well-defined, hindering progress towards identification of therapeutic targets.

Methods

We collected fresh patient samples and performed single-cell transcriptomic profiling of solid metastatic tissue (Bone Met), liquid bone marrow at the vertebral level of spinal cord compression (Involved), and liquid bone marrow from a different vertebral body distant from the tumor site but within the surgical field (Distal), as well as bone marrow from patients undergoing hip replacement surgery (Benign). In addition, we incorporated single-cell data from primary ccRCC tumors (ccRCC Primary) for comparative analysis.

Results

The bone marrow of metastatic patients is immune-suppressive, featuring increased, exhausted CD8 + cytotoxic T cells, T regulatory cells, and tumor-associated macrophages (TAM) with distinct transcriptional states in metastatic lesions. Bone marrow stroma from tumor samples demonstrated a tumor-associated mesenchymal stromal cell population (TA-MSC) that appears to be supportive of epithelial-to mesenchymal transition (EMT), bone remodeling, and a cancer-associated fibroblast (CAFs) phenotype. This stromal subset is associated with poor progression-free and overall survival and also markedly upregulates bone remodeling through the dysregulation of RANK/RANKL/OPG signaling activity in bone cells, ultimately leading to bone resorption.

Conclusions

These results provide a comprehensive analysis of the bone marrow niche in the setting of human metastatic cancer and highlight potential therapeutic targets for both cell populations and communication channels.
Male versus female inflammatory response after brain death model followed by ex vivo lung perfusion
Authors: Ricardo-da-Silva Fernanda Yamamoto , Armstrong-Jr Roberto , Ramos Mayara Munhoz de Assis , Vidal-dos-Santos Marina , Jesus Correia Cristiano , Ottens Petra J. , Moreira Luiz Felipe Pinho , Leuvenink Henri G. D. , Breithaupt-Faloppa Ana Cristina
Published: January 2024

Background

Ex vivo lung perfusion (EVLP) is a useful tool for assessing lung grafts quality before transplantation. Studies indicate that donor sex is as an important factor for transplant outcome, as females present higher inflammatory response to brain death (BD) than males. Here, we investigated sex differences in the lungs of rats subjected to BD followed by EVLP.

Methods

Male and female Wistar rats were subjected to BD, and as controls sham animals. Arterial blood was sampled for gas analysis. Heart–lung blocks were kept in cold storage (1 h) and normothermic EVLP carried out (4 h), meanwhile ventilation parameters were recorded. Perfusate was sampled for gas analysis and IL-1β levels. Leukocyte infiltration, myeloperoxidase presence, IL-1β gene expression, and long-term release in lung culture (explant) were evaluated.

Results

Brain dead females presented a low lung function after BD, compared to BD-males; however, at the end of the EVLP period oxygenation capacity decreased in all BD groups. Overall, ventilation parameters were maintained in all groups. After EVLP lung infiltrate was higher in brain dead females, with higher neutrophil content, and accompanied by high IL-1β levels, with increased gene expression and concentration in the culture medium (explant) 24 h after EVLP. Female rats presented higher lung inflammation after BD than male rats. Despite maintaining lung function and ventilation mechanics parameters for 4 h, EVLP was not able to alter this profile.

Conclusion

In this context, further studies should focus on therapeutic measures to control inflammation in donor or during EVLP to increase lung quality.