bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression signature and molecular basis of CDH11 in OSCC detected by a combination of multiple methods
Authors: Wei Yuxing , Cheng Xujie , Deng Limei , Dong Hao , Wei Huiping , Xie Cheng , Tuo Yangjuan , Li Guangyu , Yu Dahai , Cao Yong
Published: April 2023

Oral squamous cell carcinoma (OSCC) is one of the most common malignancy in the oral cancer threatening human health and the survival rate of OSCC has not been effectively improved in recent decades, so more effective biomarkers for the targeted therapy of OSCC are needed. Moreover, the role of CDH11 in OSCC has not been intensively investigated. We here show that the CDH11 protein and mRNA expression levels in the OSCC tissues were all significantly higher than in the non-cancerous tissues using RT-qPCR and western blot. This study also revealed that patients with higher CDH11 levels showed a higher incidence of perineural invasion and lymph node metastasis. By using data available from the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and ArrayExpress databases, overexpressed CDH11 in OSCC that associated with patients’history of alcohol, negative Human Papilloma Virus (HPV) status, perineural invasion, infiltration of multiple immune cells, and Single-cell functional states including quiescence and angiogenesis, possessed an excellent discriminatory capability in the OSCC patients. Moreover, the majority of the biological processes or pathways were significantly clustered by co-expressed genes, including extracellular matrix organization, the epithelial to mesenchymal transition, carbon metabolism, and the PI3K-Akt signaling pathway, and the upstream transcriptional regulation mechanism of CDH11 in OSCC was showed on a transcription factor/miRNA-mRNA network with the online tool NetworkAnalyst. Finally, frequent mutation of CDH11 was observed on a mouse OSCC model through whole-genome sequencing. CDH11 might serve as a valuable biomarker in OSCC, as it was identified to be overexpressed in OSCC and related to its clinical progression.
Morphologically intact airways in lung fibrosis have an abnormal proteome
Authors: Herrera Jeremy A. , Dingle Lewis A. , Monetero M. Angeles , Venkateswaran Rajamiyer V. , Blaikley John F. , Granato Felice , Pearson Stella , Lawless Craig , Thornton David J.
Published: April 2023

Honeycombing is a histological pattern consistent with Usual Interstitial Pneumonia (UIP). Honeycombing refers to cystic airways located at sites of dense fibrosis with marked mucus accumulation. Utilizing laser capture microdissection coupled mass spectrometry (LCM-MS), we interrogated the fibrotic honeycomb airway cells and fibrotic uninvolved airway cells (distant from honeycomb airways and morphologically intact) in specimens from 10 patients with UIP. Non-fibrotic airway cell specimens from 6 patients served as controls. Furthermore, we performed LCM-MS on the mucus plugs found in 6 patients with UIP and 6 patients with mucinous adenocarcinoma. The mass spectrometry data were subject to both qualitative and quantitative analysis and validated by immunohistochemistry. Surprisingly, fibrotic uninvolved airway cells share a similar protein profile to honeycomb airway cells, showing deregulation of the slit and roundabout receptor (Slit and Robo) pathway as the strongest category. We find that (BPI) fold-containing family B member 1 (BPIFB1) is the most significantly increased secretome-associated protein in UIP, whereas Mucin-5AC (MUC5AC) is the most significantly increased in mucinous adenocarcinoma. We conclude that fibrotic uninvolved airway cells share pathological features with fibrotic honeycomb airway cells. In addition, fibrotic honeycomb airway cells are enriched in mucin biogenesis proteins with a marked derangement in proteins essential for ciliogenesis. This unbiased spatial proteomic approach generates novel and testable hypotheses to decipher fibrosis progression.
Visceral adipose tissue is an independent predictor and mediator of the progression of coronary calcification: a prospective sub-analysis of the GEA study
Authors: Antonio-Villa Neftali Eduardo , Juárez-Rojas Juan Gabriel , Posadas-Sánchez Rosalinda , Reyes-Barrera Juan , Medina-Urrutia Aida
Published: April 2023

Background

Coronary artery calcium (CAC) improves cardiovascular event prediction. Visceral adipose tissue (VAT) is a cardiometabolic risk factor that may directly or through its related comorbidities determine the obesity-related risk. A clinical VAT estimator could allow an efficient evaluation of obesity-related risk. We aimed to analyze the effect of VAT and its related cardiometabolic risk factors on CAC progression.

Methods

CAC was quantified at baseline and after 5 years by computed tomography (CT), determining its progression. VAT and pericardial fat were measured by CT and estimated by a clinical surrogate (METS-VF). Considered cardiometabolic risk factors were: peripheral insulin resistance (IR), HOMA-IR, adipose tissue IR (ADIPO-IR), and adiponectin. Factors independently associated to CAC progression were analyzed by adjusted Cox proportional hazard models, including statin use and ASCVD risk score as covariates. We performed interaction and mediation models to propose possible pathways for CAC progression.

Results

The study included 862 adults (53 ± 9 years, 53% women), incidence CAC progression rate: 30.2 (95% CI 25.3–35.8)/1000 person-years. VAT (HR: 1.004, 95% CI 1.001–1.007, p < 0.01) and METS-VF (HR: 1.001, 95% CI 1.0–1.001, p < 0.05) independently predicted CAC progression. VAT-associated CAC progression risk was evident among low-risk ASCVD subjects, and attenuated among medium–high-risk subjects, suggesting that traditional risk factors overcome adiposity in the latter. VAT mediates 51.8% (95% CI 44.5–58.8%) of the effect attributable to IR together with adipose tissue dysfunction on CAC progression.

Conclusions

This study supports the hypothesis that VAT is a mediator of the risk conferred by subcutaneous adipose tissue dysfunction. METS-VF is an efficient clinical surrogate that could facilitate the identification of at-risk adiposity subjects in daily clinical practice.
Mechanism of lnRNA-ICL involved in lung cancer development in COPD patients through modulating microRNA-19-3p/NKRF/NF-κB axis
Authors: Lu Jingjing , Shi Yan , Zhang Feng , Zhang Ying , Zhao Xiangwang , Zheng Haiyan , Li Lingyu , Zhao Shiqiao , Zhao Liming
Published: April 2023

The incidence of lung cancer (LC) in chronic obstructive pulmonary disease (COPD) patients is dozens of times higher than that in patients without COPD. Elevated activity of nuclear factor-k-gene binding (NF-κB) was found in lung tissue of patients with COPD, and the continuous activation of NF-κB is observed in both malignant transformation and tumor progression of LC, suggesting that NF-κB and its regulators may play a key role in the progression of LC in COPD patients. Here, we report for the first time that a key long non-coding RNA (lncRNA)-ICL involved in the regulation of NF-κB activity in LC tissues of COPD patients. The analyses showed that the expression of ICL significantly decreased in LC tissues of LC patients with COPD than that in LC tissues of LC patients without COPD. Functional experiments in vitro showed that exogenous ICL only significantly inhibited the proliferation, invasion and migration in primary tumor cells of LC patients with COPD compared to LC patients without COPD. Mechanism studies have shown that ICL could suppress the activation of NF-κB by blocking the hsa-miR19-3p/NKRF/NF-κB pathway as a microRNA sponge. Furthermore, In vivo experiments showed that exogenous ICL effectively inhibited the growth of patient-derived subcutaneous tumor xenografts (PDX) of LC patients with COPD and significantly prolonged the survival time of tumor-bearing mice. In a word, our study shows that the decrease of ICL is associated with an increased risk of LC in patients with COPD, ICL is not only expected to be a new therapeutic target for LC in COPD patients, but also has great potential to be used as a new marker for evaluating the occurrence, severity stratification and prognosis of LC in patients with COPD.
Does adjuvant hepatic artery infusion chemotherapy improve patient outcomes for hepatocellular carcinoma following liver resection? A meta-analysis
Authors: Hu Lingbo , Zheng Yu , Lin Jiangyin , Shi Xingpeng , Wang Aidong
Published: April 2023

Background

Adjuvant hepatic artery infusion chemotherapy (HAIC) has been shown to be beneficial to the patient outcomes in hepatocellular carcinoma (HCC).

Methods

Randomized controlled trials (RCTs) and non-RCTs were identified from six databases up to January 26, 2023. Patient outcomes were assessed using overall survival (OS) and disease-free survival (DFS). Data were presented as hazard ratios (HR, 95% confidence intervals, or CIs).

Results

The present systematic review included 2 RCTs and 9 non-RCTs with a total of 1290 cases. Adjuvant HAIC improved OS (HR of 0.69; 95% CI of 0.56–0.84; p < 0.01) and DFS (HR of 0.64; 95% CI of 0.49–0.83; p < 0.01). Subgroup analysis showed that HCC patients with portal vein invasion (PVI) or microvascular invasion (MVI) benefit from adjuvant HAIC in terms of OS ((HR of 0.43; 95% CI of 0.19–0.95; p < 0.01) and (HR of 0.43; 95% CI of 0.19–0.95; p = 0.0373), respectively) and DFS ((HR of 0.38; 95% CI of 0.21–0.69; p < 0.01) and (HR of 0.73; 95% CI of 0.60–0.88; p = 0.0125), respectively). Adjuvant HAIC with the oxaliplatin-based approach significantly improved OS (HR of 0.60; 95% CI of 0.36–0.84; p = 0.02) and (HR of 0.59; 95% CI of 0.43–0.75; p < 0.01), respectively).

Conclusion

This meta-analysis demonstrated that postoperative adjuvant HAIC was beneficial in HCC patients with PVI and MVI. It remains unclear whether HAIC can improve the survival outcome in all HCC patients after hepatic resection.
Emerging healthy lifestyle factors and all-cause mortality among people with metabolic syndrome and metabolic syndrome-like characteristics in NHANES
Authors: Niu Mengying , Chen Jiahao , Hou Rongyao , Sun Yu , Xiao Qi , Pan Xudong , Zhu Xiaoyan
Published: April 2023

Background

The impact of integrated lifestyles on health has attracted a lot of attention. It remains unclear whether adherence to low-risk healthy lifestyle factors is protective in individuals with metabolic syndrome and metabolic syndrome-like characteristics. We aimed to explore whether and to what extent overall lifestyle scores mitigate the risk of all-cause mortality in individuals with metabolic syndrome and metabolic syndrome-like characteristics.

Methods

In total, 6934 participants from the 2007 to 2014 National Health and Nutrition Examination Survey (NHANES) were included. The weighted healthy lifestyle score was constructed based on smoking, alcohol consumption, physical activity, diet, sleep duration, and sedentary behavior information. Generalized linear regression models and restricted cubic splines were used to analyze the association between healthy lifestyle scores and all-cause mortality. ​

Results

Compared to participants with relatively low healthy lifestyle scores, the risk ratio (RR) in the middle healthy lifestyle score group was 0.51 (RR = 0.51, 95% CI 0.30–0.88), and the high score group was 0.26 (RR = 0.26, 95% CI 0.15–0.48) in the population with metabolic syndrome. The difference in gender persists. In females, the RRs of the middle and high score groups were 0.47 (RR = 0.47, 95% CI 0.23–0.96) and 0.21 (RR = 0.21, 95% CI 0.09–0.46), respectively. In males, by contrast, the protective effect of a healthy lifestyle was more pronounced in the high score group (RR = 0.33, 95% CI 0.13–0.83) and in females, the protective effects were found to be more likely. The protective effect of a healthy lifestyle on mortality was more pronounced in those aged < 65 years. Higher lifestyle scores were associated with more prominent protective effects, regardless of the presence of one metabolic syndrome factor or a combination of several factors in 15 groups. What's more, the protective effect of an emerging healthy lifestyle was more pronounced than that of a conventional lifestyle.

Conclusions

Adherence to an emerging healthy lifestyle can reduce the risk of all-cause mortality in people with metabolic syndrome and metabolic syndrome-like characteristics; the higher the score, the more obvious the protective effect. Our study highlights lifestyle modification as a highly effective nonpharmacological approach that deserves further generalization.
The roles of dietary lipids and lipidomics in gut-brain axis in type 2 diabetes mellitus
Authors: Ağagündüz Duygu , Icer Mehmet Arif , Yesildemir Ozge , Koçak Tevfik , Kocyigit Emine , Capasso Raffaele
Published: April 2023

Type 2 diabetes mellitus (T2DM), one of the main types of Noncommunicable diseases (NCDs), is a systemic inflammatory disease characterized by dysfunctional pancreatic β-cells and/or peripheral insulin resistance, resulting in impaired glucose and lipid metabolism. Genetic, metabolic, multiple lifestyle, and sociodemographic factors are known as related to high T2DM risk. Dietary lipids and lipid metabolism are significant metabolic modulators in T2DM and T2DM-related complications. Besides, accumulated evidence suggests that altered gut microbiota which plays an important role in the metabolic health of the host contributes significantly to T2DM involving impaired or improved glucose and lipid metabolism. At this point, dietary lipids may affect host physiology and health via interaction with the gut microbiota. Besides, increasing evidence in the literature suggests that lipidomics as novel parameters detected with holistic analytical techniques have important roles in the pathogenesis and progression of T2DM, through various mechanisms of action including gut-brain axis modulation. A better understanding of the roles of some nutrients and lipidomics in T2DM through gut microbiota interactions will help develop new strategies for the prevention and treatment of T2DM. However, this issue has not yet been entirely discussed in the literature. The present review provides up-to-date knowledge on the roles of dietary lipids and lipidomics in gut-brain axis in T2DM and some nutritional strategies in T2DM considering lipids- lipidomics and gut microbiota interactions are given.
ARIH1 inhibits influenza A virus replication and facilitates RIG-I dependent immune signaling by interacting with SQSTM1/p62
Authors: Wang Shengyu , Li Zhenrong , Chen Yaping , Gao Sanli , Qiao Junhua , Liu Haoru , Song Hong , Ao Dishu , Sun Xin
Published: April 2023

Background

Multiple host factors are involved in modulating type I interferon expression induced by viruses; however, the mechanism is not fully elucidated. Influenza A virus infection causes severe respiratory symptoms and triggers a series of signaling cascades and host innate immune responses, including interferon production. The co-IP/MS technology was used to screen several antiviral factors in the early stage. Among these factors, ariadne-1 homolog (ARIH1) caught our attention.

Methods

Western blot assay was performed to detect the level of proteins and software ImageJ was used to analyze the band intensities. Polymerase activity assay was conducted to evaluate the polymerase activity of influenza A virus. Tissue culture infective dose (TCID50) assay was performed to measure influenza A virus titers, and quantitative RT-PCR assay was applied to test the mRNA level of IFN-β, ISG56, and CXCL10. Luciferase reporter assay was used to confirm the target of ARIH1 in RIG-I signaling. Immunoprecipitation assay was performed to detect the interaction and the ubiquitination of the proteins. All data were analyzed by biostatistical methods and presented as means ± standard deviation from three independent experiments. Statistical significance was determined using two-tailed student’s t test. A P value of less than 0.05 was considered statistically significant, and a P value of less than 0.01 was considered highly significant (ns, P ≥ 0.05; *, P < 0.05; and **, P < 0.01).

Results

We found that ARIH1, a member of E3 ubiquitin ligases, enhanced cellular antiviral responses. Subsequent study showed that ARIH1 was up-regulated during influenza A virus infection. Further analysis showed that ARIH1 enhanced IFN-β and downstream gene expression by affecting the degradation of RIG-I through the SQSTM1/p62 signaling pathway.

Conclusion

This newly revealed mechanism shows that cellular response increases of ARIH1 and promotes IFN-β expression to boost host survival during viral infection.
Field-measured canopy height may not be as accurate and heritable as believed: evidence from advanced 3D sensing
Authors: Zang Jingrong , Jin Shichao , Zhang Songyin , Li Qing , Mu Yue , Li Ziyu , Li Shaochen , Wang Xiao , Su Yanjun , Jiang Dong
Published: April 2023

Canopy height (CH) is an important trait for crop breeding and production. The rapid development of 3D sensing technologies shed new light on high-throughput height measurement. However, a systematic comparison of the accuracy and heritability of different 3D sensing technologies is seriously lacking. Moreover, it is questionable whether the field-measured height is as reliable as believed. This study uncovered these issues by comparing traditional height measurement with four advanced 3D sensing technologies, including terrestrial laser scanning (TLS), backpack laser scanning (BLS), gantry laser scanning (GLS), and digital aerial photogrammetry (DAP). A total of 1920 plots covering 120 varieties were selected for comparison. Cross-comparisons of different data sources were performed to evaluate their performances in CH estimation concerning different CH, leaf area index (LAI), and growth stage (GS) groups. Results showed that 1) All 3D sensing data sources had high correlations with field measurement (r > 0.82), while the correlations between different 3D sensing data sources were even better (r > 0.87). 2) The prediction accuracy between different data sources decreased in subgroups of CH, LAI, and GS. 3) Canopy height showed high heritability from all datasets, and 3D sensing datasets had even higher heritability (H2 = 0.79–0.89) than FM (field measurement) (H2 = 0.77). Finally, outliers of different datasets are analyzed. The results provide novel insights into different methods for canopy height measurement that may ensure the high-quality application of this important trait.
A new type of elastic fixation, using an encircling and binding technique, for tibiofibular syndesmosis stabilization: comparison to traditional cortical screw fixation
Authors: Zhu Nan , Zhong Qigang , Zhan Junfeng , Zhang Shuo , Liu Wei , Yao Yunfeng , Jing Juehua
Published: April 2023

Background

The distal tibiofibular syndesmosis (DTS) is a complex fibrous joint that contributes to the stability and weight-bearing function of the ankle. As such, repair of DTS injury is required, providing fixation strength while maintaining ankle range of motion. The aim of this study was to compare a new elastic fixation technique, using an encircling and binding technique, for DTS stabilization, compared to the traditional cortical bone screw fixation.

Methods

This was a retrospective analysis of 67 patients treated for a DTS injury at our hospital, between June 2019 and June 2021. Of them, 33 were treated with encircling and binding (EB group) and 34 using a cortical screw (CS group). The following outcomes were compared between groups: time to inferior tibiofibular fixation; length of hospital stay; time to partial weight bearing; time to complete weight bearing; complications; imaging data; and functional scores.

Results

Successful stabilization was achieved in all cases, with a mean follow-up period of 15.78 ± 2.97 months. Time to fixation and time to partial and complete weight bearing were shorter for the EB than that for the CS group. The length of hospital was not different between groups. With regard to complications, a superficial infection developed in one patient in each group, with wound healing achieved after active treatment. Screw fracture occurred in two patients in the CS group. At 3 months post-surgery, the American Foot Surgery Association Ankle-Hindfoot score (AOFAS) was higher and the pain score lower for the EB than that for the CS group, but with no between-group difference at the final follow-up. On imaging, the tibiofibular clear space and tibiofibular overlap were not different between groups.

Conclusions

DTS fixation using encircling and binding yielded better clinical and functional outcomes than did cortical screw fixation at 3 months post-surgery, with no difference at the final follow-up. This novel fixation technique provides firm fixation, combined with earlier return to postoperative exercise and recovery of ankle function.
Effect of subanesthetic dose of esketamine on postoperative rehabilitation in elderly patients undergoing hip arthroplasty
Authors: Min Menghang , Du Chengxu , Chen Xiaoying , Xin Wenqi
Published: April 2023

Objective

The majority of individuals with femoral neck fractures opt for total hip replacement to enhance their quality of life. However, this group frequently exhibits perioperative symptoms of pain, anxiety, and sadness, which extends recovery time to some extent. Esketamine, the right-handed monomer of ketamine, is more popular these days due to its sedative, analgesic, and antidepressant properties. There are currently few domestic and international research on the use of esketamine in elderly individuals who have undergone surgery for a femoral neck fracture. In order to further cut the length of the hospital stay and hasten postoperative recovery, this study investigates whether esketamine postoperative analgesia can lessen postoperative pain, anxiety, and depression in older patients having hip replacement.

Methods

150 patients, ASA physical status I–II, aged ≥ 60 years, no limitation in gender, BMI 18–25 kg/cm2, who underwent selective total hip arthroplasty, according to random number table method, esketamine group (group A) and sufentanil group (group B) were randomized, 75 patients in each group. The two groups received general anesthesia method. At the end of the operation, PCIA was connected for analgesia. In group A, esketamine 2.5 mg/kg was mixed with normal saline to 100 ml. In group B, sufentanil 2.5 ug/kg was mixed with normal saline to 100 ml. Record the VAS scores after operation. Record the first ambulation time, ambulation distance and Patient-controlled Analgesia compression times after operation. The incidence of postoperative adverse reactions such as drowsiness, dizziness, nausea and vomiting, multilingual were recorded. ELISA was used to detect IL-6 and CRP in the morning, 24 h and 72 h after operation. The Hospital Anxiety and Depression Scale (HAD) score and Harris score at 3 days, 1 week and 1 month after operation were followed up.

Results

There was no significant difference in VAS score and PCA compression times (P > 0.05), but the incidence of nausea, vomiting and dizziness in group B was higher than that in group A (P < 0.05). Compared with group B, the levels of IL-6 and CRP in group A at 24 h and 72 h after operation were significantly decreased (P < 0.05). Postoperative ambulation time and ambulation distance in group A were better than those in group B (P < 0.05). The HAD score of group A was lower than that of group B at 3 days and 1 week after operation (P < 0.05). However, there was no significant difference between the two groups at 1 month after operation (P > 0.05). The Harris score of group A was higher than that of group B at 3 days, 1 week and 1 month after operation (P < 0.05).

Conclusions

Esketamine can reduce short-term postoperative anxiety and depression, relieve postoperative pain and stress response, shorten bed rest time after total hip replacement, and accelerate postoperative recovery.
Comparison of three common shoulder injections for rotator cuff tears: a systematic review and network meta-analysis
Authors: Jiang Xinzhao , Zhang Hong , Wu Qing , Chen Yun , Jiang Tian
Published: April 2023

Objective

To compare the clinical effectiveness of three common shoulder injections mentioned in the guidelines [corticosteroid, sodium hyaluronate (SH) and platelet-rich plasma (PRP)] on rotator cuff tears.

Material and methods

The PubMed, Embase and Cochrane Library databases were systematically searched up to June 1, 2022, for randomized controlled trials (RCTs) and prospective studies on the three injection therapies for rotator cuff tears. The main results were pain relief and functional improvement at 1–5 months and over 6 months, pooled using a network meta-analysis and ranked by SUCRA score. The risk of bias of the included studies was assessed using the Cochrane Collaboration tool.

Results

Twelve RCTs and 4 prospective studies comprising a total of 1115 patients were included in the review. Three prospective studies were judged to be at high risk of selection bias and performance bias, and one was considered as having a high risk of detection bias. SH injection ranked first in the short term in pain relief (MD: − 2.80; 95%CI − 3.91, − 1.68) and functional improvement (MD:19.17; 95%CI 12.29, 26.05), while PRP injection obtained better results in the long term in both pain relief (MD: − 4.50; 95%CI − 4.97, − 4.03) and functional improvement (MD:11.11; 95%CI 0.53,21.68).

Conclusions

PRP injection has the potential to successfully treat rotator cuff tears as an alternative to corticosteroids in the long term, in terms of either therapeutic efficiency or adverse effects, followed by SH injection. More research is needed to make high-quality recommendations on treatment options for injection treatments of rotator cuff tears.
Robot-assisted percutaneous pars–pedicle screw fixation for treating Hangman’s fracture
Authors: Zhao Jingwei , Liu Yajun , Zhang Qi , Fan Mingxing , Han Xiaoguang , He Da , Liu Bo , Tian Wei
Published: April 2023

Background

This study aimed to evaluate the safety and efficacy of robot-assisted percutaneous pars–pedicle screw fixation surgery for treating Hangman’s fracture.

Methods

The study involved 33 patients with Hangman’s fracture who underwent robot-assisted fixation surgery using cannulated pars–pedicle screws through a percutaneous approach. The primary parameter evaluated was the accuracy of the screws according to the Gertzbein–Robbins scale, using postoperative CT images. Secondary parameters included the duration of surgery, intraoperative blood loss, postoperative hospital stay, and neurovascular injury.

Results

A total of 60 pars–pedicle screws were placed in 33 patients. Based on the Levine and Edwards classification, the patients included 12 cases of type I, 15 cases of type II, five cases of type IIa, and one atypical case. The average operative time was 92.4 ± 37.4 min, and the average blood loss was 22.4 ± 17.9 ml. Fifty-five of 60 screws were successfully placed within the bone. No screw-related neurovascular injury was observed, and satisfactory reduction was achieved in all cases.

Conclusion

Robot-assisted percutaneous pars–pedicle screw fixation is a safe and feasible method for treating Hangman’s fracture.

Trial registration: The study was retrospectively registered and approved by our center’s institutional review board.
Multidisciplinary paper on patient blood management in cardiothoracic surgery in the UK: perspectives on practice during COVID-19
Authors: Al-Attar Nawwar , Gaer Jullien , Giordano Vincenzo , Harris Emma , Kirk Alan , Loubani Mahmoud , Meybohm Patrick , Sayeed Rana , Stock Ulrich , Travers Jennifer , Whiteman Becky
Published: April 2023

The coronavirus (COVID-19) pandemic disrupted all surgical specialties significantly and exerted additional pressures on the overburdened United Kingdom (UK) National Health Service. Healthcare professionals in the UK have had to adapt their practice. In particular, surgeons have faced organisational and technical challenges treating patients who carried higher risks, were more urgent and could not wait for prehabilitation or optimisation before their intervention. Furthermore, there were implications for blood transfusion with uncertain patterns of demand, reductions in donations and loss of crucial staff because of sickness and public health restrictions. Previous guidelines have attempted to address the control of bleeding and its consequences after cardiothoracic surgery, but there have been no targeted recommendations in light of the recent COVID-19 challenges. In this context, and with a focus on the perioperative period, an expert multidisciplinary Task Force reviewed the impact of bleeding in cardiothoracic surgery, explored different aspects of patient blood management with a focus on the use of haemostats as adjuncts to conventional surgical techniques and proposed best practice recommendations in the UK.
lncRNA-FMR6 directly binds SAV1 to increase apoptosis of granulosa cells in premature ovarian failure
Authors: Bao Dongqin , Gao Lei , Xin Haiyan , Wang Lie
Published: April 2023

Background

A regulatory mechanism of lncRNA binding to protein has been detected in premature ovarian failure (POF). Therefore, this study was expected to illustrate the mechanism of lncRNA-FMR6 and SAV1 regulating POF.

Methods

Follicular fluid and ovarian granulosa cells (OGCs) from POF patients and healthy volunteers were collected. Using RT-qPCR and western blotting, lncRNA-FMR6 and SAV1 expression were detected. KGN cells were cultured, and the subcellular localization analysis of lncRNA-FMR6 was carried out. In addition, KGN cells were treated with lncRNA-FMR6 knockdown/overexpression or SAV1 knockdown. Then, cell optical density (proliferation), apoptosis rate, Bax and Bcl-2 mRNA expression were explored by CCK-8, caspase-3 activity, flow cytometry and RT-qPCR analysis. By performing RIP and RNA pull-down experiments, the interactions among lncRNA-FMR6 and SAV1 was investigated.

Results

Up-regulation of lncRNA-FMR6 was shown in follicular fluid and OGCs of POF patients, and ectopic overexpression of lncRNA-FMR6 promoted KGN cells apoptosis and inhibited proliferation. lncRNA-FMR6 was localized in the cytoplasm of KGN cells. SAV1 bounding to lncRNA-FMR6 was negatively regulated by lncRNA-FMR6, and was down-regulated in POF. SAV1 knockdown promoted KGN cells proliferation and inhibited apoptosis, and partially eliminated the effect of lncRNA-FMR6 low expression on KGN cells.

Conclusion

Overall, lncRNA-FMR6 accelerates POF progression by binding to SAV1.
A cluster randomised, 16-week, parallel-group multicentre trial to compare the effectiveness of a digital school-based cognitive behavioural resilience/wellbeing-building intervention targeting emotional and behavioural problems in vulnerable Year 4 primary school children in whole classes, to the usual school curriculum: a study protocol to the “CUES for Schools” trial
Authors: Jolley S. , Lord J. , Plant D. , Wood E. , Bracegirdle K. , Browning S. , Carter B. , James K.
Published: April 2023

Background

Around 10% of school-aged children experience mental health difficulties. Many more are ‘vulnerable’: experiencing emotional and/or behavioural problems reaching clinical levels, and thus at greatest risk of future mental illness. The trial aim is to evaluate the effectiveness of the CUES for schools programme in reducing emotional and behavioural problems in vulnerable children.

Methods

The “CUES for Schools” study is a multicentre cluster randomised controlled trial in primary schools in south east England. Schools will be randomised to receive the usual school curriculum, or the CUES programme (1:1). We aim to enrol 74 schools (5550 children including 2220 vulnerable children). CUES is a whole-class teacher-facilitated interactive digital cognitive-behavioural intervention, delivered as 24 short (20-min) modules over 12 weeks, targeting emotional/behavioural regulation skills. Children self-report emotional/behavioural problems at baseline, 8, and 16 weeks, and wellbeing and cognitive vulnerability at 0 and 16 weeks. Adverse events are assessed at 8 and 16 weeks. Teachers rate classroom behaviour at baseline and 16 weeks. School senior leadership teams and individual teachers consent to involvement in the study; parents can opt their child out of CUES sessions, assessments, or research. Children can similarly opt out and assent to research participation. The primary objective of this trial is to evaluate the effectiveness of CUES for schools compared to the usual school curriculum in improving emotional/behavioural problems for vulnerable Year 4 (8–9 years old) children at 16 weeks post-randomisation, as measured using a standardised questionnaire designed for primary schools. The secondary objective is to investigate the impact of the CUES for schools programme on both vulnerable and non-vulnerable children on wellbeing and teacher-rated classroom behaviour.

Discussion

The study will show whether CUES for schools is more effective than the usual curriculum in reducing emotional and behavioural problems in vulnerable Year 4 children, and thus reducing the risk of mental health difficulties in later adolescent and adult life. As a digital, teacher-facilitated intervention, CUES for schools can be readily implemented, at minimal cost. If effective, CUES for schools therefore has the potential to reduce the impact of emotional/behavioural difficulties on children’s learning, behaviour, and relationships and the burden of future mental health morbidity.

Trial registration

Trial Registration ISRCTN11445338. Registered on September 12, 2022.
Does hyperglycemia affect arginine metabolites in critically ill patients? A prospective cohort and in vitro study
Authors: Lee Tien F. , Tommasi Sara , Bersten Andrew , Heilbronn Leonie K. , Sotgia Salvatore , Zinellu Angelo , Carru Ciriaco , Mangoni Arduino A. , Burt Morton G.
Published: April 2023

Background

Changes in the arginine metabolites asymmetric dimethyl-L-arginine (ADMA) and L-homoarginine and acute blood glucose concentrations have been shown to cause endothelial dysfunction and be independently associated with mortality in Intensive Care Unit (ICU) patients. The aim of this study was to investigate whether hyperglycemia potentially modulates these arginine metabolite concentrations to provide a mechanism that may link hyperglycemia and mortality in this patient group.

Methods

A clinical and in vitro study were undertaken. Glucose, glycosylated hemoglobin-A1c (HbA1c) and the stress hyperglycemia ratio (SHR) (to quantify absolute, chronic and relative hyperglycemia respectively) were measured in 1155 acutely unwell adult patients admitted to a mixed medical-surgical ICU. SHR was calculated by dividing the admission glucose by the estimated average glucose over the last 3 months, which was derived from HbA1c. ADMA and l-homoarginine were measured in a plasma sample collected at admission to ICU by liquid chromatography tandem mass spectrometry. The activity of dimethylarginine-dimethylaminohydrolase 1 (DDAH1), the main enzyme regulating ADMA concentrations, was assessed at varying glucose concentrations in vitro by quantifying the conversion of ADMA to citrulline in HEK293 cells that overexpress DDAH1.

Results

In the clinical study, plasma ADMA was not significantly associated with any measure of hyperglycemia. L-homoarginine was positively associated with glucose (β = 0.067, p = 0.018) and SHR (β = 0.107, p < 0.001) after correction for glomerular filtration rate. However, as l-homoarginine is a negative predictor of mortality, the direction of these associations are the opposite of those expected if hyperglycemia was affecting mortality via changes in l-homoarginine. In vitro DDAH1 activity was not significantly influenced by glucose concentrations (p = 0.506).

Conclusion

In critically ill patients the association between relative hyperglycemia and mortality is not mediated by changes in ADMA or L-homoarginine.

Trial registration ANZCTR Trial ID ACTRN12615001164583.
The changing landscape of drug clinical trials on cardiometabolic diseases in China, 2009–2021
Authors: Li Chen , Hao Jun , Zheng Yitian , Wang Chuangshi , Yang Jie , Wang Wenyao , Zhang Kuo , Shao Chunli , Hui Wen , Wang Jiancheng , Li Wei , Tang Yi-Da
Published: April 2023

Background

Cardiometabolic disease is a clinical syndrome characterized by multiple metabolic disorders, with atherosclerosis as the core and cardiovascular and cerebrovascular events as the outcome. Drug research and development (R&D) in cardiometabolic diseases has grown rapidly worldwide. However, the development of cardiometabolic drug clinical trials in China remains unclear. This study aims to depict the changing landscape of drug clinical trials for cardiometabolic diseases in China during 2009–2021.

Methods

The detailed information of drug trials on cardiometabolic diseases registered in the National Medical Products Administration (NMPA) Registration and Information Disclosure Platform was collected between January 1, 2009, and July 1, 2021. The landscape of cardiometabolic drug clinical trials was analyzed by the characteristics, time trends, indications, pharmacological mechanisms, and geographical distribution.

Results

A total of 2466 drug clinical trials on cardiometabolic diseases were extracted and analyzed. The annual number of drug trials increased rapidly in the past twelve years. Among all the trials, the bioequivalence trials (1428; 58.3%) accounted for the largest proportion, followed by phase I (555; 22.5%), phase III (278; 11.3%), phase II (169; 6.9%), and phase IV (26; 1.1%). Of 2466 trials, 2133 (86.5%) trials were monomer drugs, only 236 (9.6%) trials were polypills and 97 (3.9%) were traditional Chinese medicine (TCM) compounds. In terms of pharmacological mechanisms, the number of trials in dihydropyridine (DHP) calcium antagonists 321 (11.9%) ranked first, while trials in angiotensin receptor blocker (ARB) 289 (10.7%) and dipeptidyl peptidase-4 (DPP-4) inhibitor 205 (7.6%) ranked second and third place respectively. Of 236 chemical polypills trials, 23 (9.7%) polypills were the combination of DHP calcium antagonists and statins, while others were the combination of two same pharmacological effect agents. As for the geographical distribution of leading units, 36 trials were led by principal investigators (PI) units from Beijing, followed by Jiangsu (n = 29), Shanghai (n = 19), Guangdong (n = 19), and Hunan (n = 19), showing an uneven regional distribution.

Conclusions

Great progress has been made in drug clinical trials on cardiometabolic diseases, especially in antihypertensive agents, hypoglycemic agents, and hypolipidemic agents. However, the insufficient innovation of first-in-class drugs and polypills should be carefully considered by all stakeholders in drug trials.
Cardiometabolic risk indicators in individuals with bipolar disorders: a replication study
Authors: Najar Hemen , Karanti Alina , Pålsson Erik , Landén Mikael
Published: April 2023

Objectives

We recently conducted the first longitudinal study comparing cardiometabolic risk indicators (CMRIs) between a cohort of individuals with bipolar disorders (BDs) and controls from the general population. Here, we sought to validate the findings in that study using an independent case-control sample.

Methods

We used data from the St. Göran project’s Gothenburg cohort. The BDs group and the control group were examined at baseline and after a median of eight and seven years, respectively. Data collection occurred between March 2009 and June 2022. We used multiple imputation to handle missing data and linear mixed effects model to examine the annual change in CMRIs over the study period.

Results

The baseline cohort included 407 individuals with BDs (mean age 40 years, 63% women) and 56 controls (mean age 43 years, 54% women). Of those, 63 persons with BDs and 42 controls participated at follow-up. At baseline, individuals with BDs had significantly higher mean values of body mass index (β = 0.14, p = 0.003) than controls. Over the study period, the difference in average annual change between the patient and the control group indicated an increase in patients relative to controls in waist-to-hip ratio (0.004 unit/year, p = 0.01), diastolic (0.6 mm Hg/year, p = 0.048), and systolic (0.8 mm Hg/year, p = 0.02) blood pressure.

Conclusions

This study replicated the main findings from our previous study and showed that central obesity and measures of blood pressure worsened over a relatively short time in individuals with BDs relative to controls. It is vital for clinicians to monitor CMRIs in persons with BDs and to be proactive in preventing cardiometabolic diseases in this high-risk group.
The experience and influence of fear after anterior cruciate ligament reconstruction: an interview study with young athletes
Authors: Kvist Joanna , Bengtsson Johanna , Lundqvist Carolina
Published: April 2023

Background

Despite good physical function, many athletes do not return to sports after an anterior cruciate ligament reconstruction (ACLR). One important reason for this is fear of new injury. The aim of this study was to investigate young athletes’ experiences of knee-related fear after an ACLR and how they perceive this fear to affect them in their sporting and everyday life.

Methods

A qualitative interview study was conducted, using semi-structured interviews. Athletes who were active in contact or pivoting sport before an ACL injury, with the goal of returning to the same sport and who scored highly on fear of new injury at six months post-ACLR, were asked to participate. Ten athletes (six women and four men, aged 17–25 years), were interviewed by an independent researcher, 7–9 months after ACLR. Content analysis employing an abductive approach was used.

Results

The analysis resulted in three categories with associated subcategories: 1. The expressions of fear; (i) reason for fear, (ii) changes in fear over time, and (iii) injury situation. 2. Reactions, consequences, and adaptations; (i) reactions, (ii) behavioural adaptation and influence on rehabilitation and daily life, (iii) present consequences, and (iv) consequences for the future. 3. Fear and adaptations related to returning to sports; (i) fear related to returning to sports and, (ii) adaptations in sports and life due to fear. Fear was described in broad and complex ways, with fear of a new injury being expressed as one of several aspects. Various reasons (e.g., seeing others getting injured in the past, previous experience of injury, failed rehabilitation, perceived knee instability) were given to explain the fear, and athletes reacted both physically and mentally to fear. Both positive and negative adaptations to fear were described, in both daily life and sports.

Conclusion

The results contribute to an increased understanding of fear as an essential psychological factor to consider during rehabilitation and leaves the way open for research to investigate how physiotherapists can work to manage fear better among ACLR patients.
Validation study of “Santé-Cerveau”, a digital tool for early cognitive changes identification
Authors: Lesoil Constance , Bombois Stéphanie , Guinebretiere Octave , Houot Marion , Bahrami Mahsa , Levy Marcel , Genthon Rémy , Bozon Frédérique , Jean-Marie Heidy , Epelbaum Stéphane , Foulon Pierre , Villain Nicolas , Dubois Bruno
Published: April 2023

Background

There is a need for a reliable, easy-to-use, widely available, and validated tool for timely cognitive impairment identification. We created a computerized cognitive screening tool (Santé-Cerveau digital tool (SCD-T)) including validated questionnaires and the following neuropsychological tests: 5 Word Test (5-WT) for episodic memory, Trail Making Test (TMT) for executive functions, and a number coding test (NCT) adapted from the Digit Symbol Substitution Test for global intellectual efficiency. This study aimed to evaluate the performance of SCD-T to identify cognitive deficit and to determine its usability.

Methods

Three groups were constituted including 65 elderly Controls, 64 patients with neurodegenerative diseases (NDG): 50 AD and 14 non-AD, and 20 post-COVID-19 patients. The minimum MMSE score for inclusion was 20. Association between computerized SCD-T cognitive tests and their standard equivalent was assessed using Pearson's correlation coefficients. Two algorithms (a simple clinician-guided algorithm involving the 5-WT and the NCT; and a machine learning classifier based on 8 scores from the SCD-T tests extracted from a multiple logistic regression model, and data from the SCD-T questionnaires) were evaluated. The acceptability of SCD-T was investigated through a questionnaire and scale.

Results

AD and non-AD participants were older (mean ± standard deviation (SD): 72.61 ± 6.79 vs 69.91 ± 4.86 years old, p = 0.011) and had a lower MMSE score (Mean difference estimate ± standard error: 1.74 ± 0.14, p < 0.001) than Controls; post-COVID-19 patients were younger than Controls (mean ± SD: 45.07 ± 11.36 years old, p < 0.001). All the computerized SCD-T cognitive tests were significantly associated with their reference version. In the pooled Controls and NDG group, the correlation coefficient was 0.84 for verbal memory, -0.60 for executive functions, and 0.72 for global intellectual efficiency. The clinician-guided algorithm demonstrated 94.4% ± 3.8% sensitivity and 80.5% ± 8.7% specificity, and the machine learning classifier 96.8% ± 3.9% sensitivity and 90.7% ± 5.8% specificity. The acceptability of SCD-T was good to excellent.

Conclusions

We demonstrate the high accuracy of SCD-T in screening cognitive disorders and its good acceptance even in individuals with prodromal and mild dementia stages. SCD-T would be useful in primary care to faster refer subjects with significant cognitive impairment (and limit unnecessary referrals) to specialized consultation, improve the AD care pathway and the pre-screening in clinical trials.
Several Nocardia abcessus bronchiolitis in a patient treated with inhaled corticosteroids: a case report
Authors: Cascarano Estelle , Frappa Murielle , Degano Bruno , Pelloux Isabelle , Saint-Raymond Christel , Gheerbrant Hubert
Published: April 2023

Nocardiosis is a disease that mainly affects immunocompromised patients. Inhaled corticosteroids (ICS) are standard of care for asthma. This treatment can induce respiratory infections but no case of bronchiolitis nocardiosis have been described so far. A 58-year-old man, with history of controlled moderate allergic asthma, develop an increased cought in the last two years associated with dyspnea on exertion. Within two months, although ICS were increased to high doses, symptoms worsened due to a severe obstructive ventilatory disorder as revealed by pulmonary function tests (PFT). Small-scale lesions (< 10%) were found on chest computed tomography (CT). A bronchoalveolar lavage (BAL) found Nocardia abcessus. After six months of Sulfamethoxazole/Trimethoprim, PFT results improved and chest CT became completely normal. We therefore present the case of a bronchiolitis nocardiosis with several bronchial syndrome and the only immunosuppressive factor found were ICS.