bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular characterization of extended-spectrum β-lactamase-producing Escherichia coli isolated from lower respiratory tract samples between 2002 and 2019 in the Central Slovenia region
Authors: Hrovat Katja , Molan Katja , Seme Katja , Ambrožič Avguštin Jerneja
Published: January 2024

Background

Antibiotic resistance is one of the most serious global health problems and threatens the effective treatment of bacterial infections. Of greatest concern are infections caused by extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC). The aim of our study was to evaluate the prevalence and molecular characteristics of ESBL-EC isolated over an 18-year pre-COVID period from lower respiratory tract (LRT) samples collected from selected Slovenian hospitals.

Objectives and methods

All isolates were identified by MALDI-TOF and phenotypically confirmed as ESBLs by a disk diffusion assay. Using a PCR approach, 487 non-repetitive isolates were assigned to phylogroups, sequence type groups, and clonal groups. Isolates were also screened for virulence-associated genes (VAGs) and antimicrobial resistance genes.

Results

The prevalence of ESBL-EC isolates from LRT in a large university hospital was low (1.4%) in 2005 and increased to 10.8% by 2019. The resistance profile of 487 non-repetitive isolates included in the study showed a high frequency of group 1 blaCTX-M (77.4%; n = 377), blaTEM (54.4%; n = 265) and aac(6')-Ib-cr (52%; n = 253) genes and a low proportion of blaSHV and qnr genes. Isolates were predominantly assigned to phylogroup B2 (73.1%; n = 356), which was significantly associated with clonal group ST131. The ST131 group accounted for 67.6% (n = 329) of all isolates and had a higher number of virulence factor genes than the non-ST131 group. The virulence gene profile of ST131 was consistent with that of other extraintestinal pathogenic E. coli (ExPEC) strains and was significantly associated with ten of sixteen virulence factor genes tested. Using ERIC-PCR fingerprinting, isolates with the same ERIC-profile in samples from different patients, and at different locations and sampling dates were confirmed, indicating the presence of “hospital-adapted” strains.

Conclusion

Our results suggest that the ESBL-EC isolates from LRT do not represent a specific pathotype, but rather resemble other ExPEC isolates, and may be adapted to the hospital environment. To our knowledge, this is the first study of ESBL-EC isolated from LRT samples collected over a long period of time.
Genomic diversity of β-lactamase producing Pseudomonas aeruginosa in Iran; the impact of global high-risk clones
Authors: Ahmadi Nazila , Salimizand Himen , Zomorodi Abolfazl Rafati , Abbas Jalileh Ebn , Ramazanzadeh Rashid , Haghi Fakhri , Hassanzadeh Sepideh , Jahantigh Mojdeh , Shahin Mojtaba
Published: January 2024

Background

Hospital-acquired infections caused by multidrug-resistant Pseudomonas aeruginosa incline hospital stay and costs of treatment that resulted in an increased mortality rate. The frequency of P. aeruginosa high-risk clones producing carbapenemases was investigated in our clinical samples.

Methods

In this cross-sectional study, 155 non-repetitive P. aeruginosa isolates were included from different medical centers of Iran. Antibiotic susceptibility testing was determined, and the presence of β-lactamases were sought by phenotypic and genotypic methods. The clonal relationship of all isolates was investigated, and multi-locus sequence typing (MLST) was used for finding the sequence types of carbapenemase-producers.

Results

The agent with highest percent susceptibility rate was recorded for colistin (94.9%). MOX and FOX were found both as low as 1.95% (3/155). The most frequent narrow spectrum β-lactamase was SHV with 7.7% (12/155) followed by PER, OXA-1, and TEM with the frequency of 7.1% (11/155), 3.2% (5/155), and 1.3% (2/155), respectively. Carbapenemases were detected in 28 isolates (18%). The most frequent carbapenemase was IMP with 9% (14/155) followed by NDM, 8.4% (13/155). OXA-48 and VIM were also detected both per one isolate (0.65%). MLST of carbapenem resistant P. aeruginosa isolates revealed that ST244, ST664, ST235, and ST357 were spread in subjected clinical settings. REP-PCR uncovered high genomic diversity in our clinical setting.

Conclusion

Clonal proliferation of ST235 strain plays a key role in the propagation of MDR pattern in P. aeruginosa. Our data showed that high-risk clones has distributed in Iran, and programs are required to limit spreading of these clones.
Deciphering tumor microenvironment: CXCL9 and SPP1 as crucial determinants of tumor-associated macrophage polarity and prognostic indicators
Authors: Su Xinming , Liang Chenhao , Chen Ruixiu , Duan Shiwei
Published: January 2024

The tumor microenvironment (TME) is an intricate system comprised of tumor cells and the surrounding cellular and non-cellular components, exerting a pivotal influence on the initiation and progression of tumors. Exhibiting dynamic and diverse compositions as well as functional states across various tumors and patients, a profound comprehension of its specific internal interactions is indispensable for formulating efficacious anti-cancer treatment strategies. Extensive interactions among various immune cell types within the TME are well-documented, with their phenotypes and abundances closely linked to clinical prognoses. TME research is progressing towards greater complexity and precision, yet, to date, no representative TME biomarkers suitable for clinical applications have been definitively identified and validated. In a recent study, the collaborative actions of CXCL9 and SPP1 (CXCL9:SPP1) were found to collectively dictate the polarity of tumor-associated macrophages (TAMs) within the TME, exerting profound effects on tumor progression and treatment responses. The mutually exclusive expression of CXCL9:SPP1 in the TME not only governs TAM polarity but also exhibits strong correlations with immune cell profiles, antitumor factors, and patient outcomes, significantly influencing prognosis. This article consolidates the significance and prospects of CXCL9:SPP1 as a novel indicator for tumor development and prognosis, while also proposing future research directions and addressing potential challenges in this promising field.
Lipid alterations play a role in the integration of PD-1/PD-L1 inhibitors and anlotinib for the treatment of advanced non–small-cell lung cancer
Authors: Liu Li , Zhang Shuo , Yang Hai-Yan , Zhou Chun-Hua , Xiong Yi , Yang Nong , Tian Ye
Published: January 2024

Background

Studies have shown that integrating anlotinib with programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors enhances survival rates among progressive non–small-cell lung cancer (NSCLC) patients lacking driver mutations. However, not all individuals experience clinical benefits from this therapy. As a result, it is critical to investigate the factors that contribute to the inconsistent response of patients. Recent investigations have emphasized the importance of lipid metabolic reprogramming in the development and progression of NSCLC.

Methods

The objective of this investigation was to examine the correlation between lipid variations and observed treatment outcomes in advanced NSCLC patients who were administered PD-1/PD-L1 inhibitors alongside anlotinib. A cohort composed of 30 individuals diagnosed with advanced NSCLC without any driver mutations was divided into three distinct groups based on the clinical response to the combination treatment, namely, a group exhibiting partial responses, a group manifesting progressive disease, and a group demonstrating stable disease. The lipid composition of patients in these groups was assessed both before and after treatment.

Results

Significant differences in lipid composition among the three groups were observed. Further analysis revealed 19 differential lipids, including 2 phosphatidylglycerols and 17 phosphoinositides.

Conclusion

This preliminary study aimed to explore the specific impact of anlotinib in combination with PD-1/PD-L1 inhibitors on lipid metabolism in patients with advanced NSCLC. By investigating the effects of using both anlotinib and PD-1/PD-L1 inhibitors, this study enhances our understanding of lipid metabolism in lung cancer treatment. The findings from this research provide valuable insights into potential therapeutic approaches and the identification of new therapeutic biomarkers.
A call to create integrated services to better address the needs of migrants who use drugs in Europe
Authors: van Selm Lena , White Trenton M. , Picchio Camila A. , Requena-Méndez Ana , Busz Machteld , Perez Gayo Roberto , Pouille Aline , Gelabert Pedro Mateu , Lazarus Jeffrey V.
Published: January 2024

Each year, thousands of migrants enter the EU. Data on drug use in migrant populations are scarce and inconclusive. However, several risk factors make them particularly vulnerable to engaging in problematic drug use. In this perspective, we summarize the limited information that is available on migrants who use drugs and make a case as to why it is essential to improve access to health and social services, including harm reduction services, for this population. With this aim, we call for the co-creation of integrated services that better address the needs of migrants who use drugs in Europe.
Whole-orbit radiomics: machine learning-based multi- and fused- region radiomics signatures for intravenous glucocorticoid response prediction in thyroid eye disease
Authors: Zhang Haiyang , Jiang Mengda , Chan Hoi Chi , Zhang Huijie , Xu Jiashuo , Liu Yuting , Zhu Ling , Tao Xiaofeng , Xia Duojin , Zhou Lei , Li Yinwei , Sun Jing , Song Xuefei , Zhou Huifang , Fan Xianqun
Published: January 2024

Background

Radiomics analysis of orbital magnetic resonance imaging (MRI) shows preliminary potential for intravenous glucocorticoid (IVGC) response prediction of thyroid eye disease (TED). The current region of interest segmentation contains only a single organ as extraocular muscles (EOMs). It would be of great value to consider all orbital soft tissues and construct a better prediction model.

Methods

In this retrospective study, we enrolled 127 patients with TED that received 4·5 g IVGC therapy and had complete follow-up examinations. Pre-treatment orbital T2-weighted imaging (T2WI) was acquired for all subjects. Using multi-organ segmentation (MOS) strategy, we contoured the EOMs, lacrimal gland (LG), orbital fat (OF), and optic nerve (ON), respectively. By fused-organ segmentation (FOS), we contoured the aforementioned structures as a cohesive unit. Whole-orbit radiomics (WOR) models consisting of a multi-regional radiomics (MRR) model and a fused-regional radiomics (FRR) model were further constructed using six machine learning (ML) algorithms.

Results

The support vector machine (SVM) classifier had the best performance on the MRR model (AUC = 0·961). The MRR model outperformed the single-regional radiomics (SRR) models (highest AUC = 0·766, XGBoost on EOMs, or LR on OF) and conventional semiquantitative imaging model (highest AUC = 0·760, NaiveBayes). The application of different ML algorithms for the comparison between the MRR model and the FRR model (highest AUC = 0·916, LR) led to different conclusions.

Conclusions

The WOR models achieved a satisfactory result in IVGC response prediction of TED. It would be beneficial to include more orbital structures and implement ML algorithms while constructing radiomics models. The selection of separate or overall segmentation of orbital soft tissues has not yet attained its final optimal result.
The effectiveness of an m-Health intervention on the sexual and reproductive health of in-school adolescents: a cluster randomized controlled trial in Nigeria
Authors: Akande Oluwatosin Wuraola , Muzigaba Moise , Igumbor Ehimario Uche , Elimian Kelly , Bolarinwa Oladimeji Akeem , Musa Omotosho Ibraheem , Akande Tanimola Makanjuola
Published: January 2024

Background

The implementation of the country-wide comprehensive sexuality education (CSE) curriculum among in-school adolescents remains abysmally low and mHealth-based interventions are promising. We assessed the effect of a mHealth-based CSE on the sexual and reproductive health (SRH) knowledge, attitude and behaviour of in-school adolescents in Ilorin, northcentral Nigeria.

Methods

Using schools as clusters, 1280 in-school adolescents were randomised into intervention and control groups. Data was collected at baseline (T0), immediately after the intervention (T1) and 3 months afterwards (T2) on SRH knowledge, attitude and practice of risky sexual behaviour (RSB). Data analysis included test of associations using Chi-square, independent t-test and repeated measures ANOVA. Predictors were identified using binary logistic regression.

Results

In the intervention group, there was a statistically significant main effect on mean knowledge score (F = 2117.252, p =  < 0.001) and mean attitude score (F = 148.493, p =  < 0.001) from T0 to T2 compared to the control group which showed no statistically significant main effects in knowledge (p = 0.073), attitude (p = 0.142) and RSB (p = 0.142). Though the mean RSB score declined from T0 to T2, this effect was not statistically significant (F = 0.558, p = 0.572). Post-intervention, being female was a positive predictor of good SRH knowledge; being male was a positive predictor of RSB while being in a higher-class level was a negative predictor of RSB.

Conclusion

The mHealth-based CSE was effective in improving SRH knowledge and attitude among in-school adolescents. This strategy should be strengthened to bridge the SRH knowledge and attitude gap among in-school adolescents.

Trial registration Retrospectively registered on the Pan African Clinical Trial Registry (pactr.samrc.ac.za) on 19 October 2023. Identification number: PACTR202310485136014
Decoding hand and wrist movement intention from chronic stroke survivors with hemiparesis using a user-friendly, wearable EMG-based neural interface
Authors: Meyers Eric C. , Gabrieli David , Tacca Nick , Wengerd Lauren , Darrow Michael , Schlink Bryan R. , Baumgart Ian , Friedenberg David A.
Published: January 2024

Objective

Seventy-five percent of stroke survivors, caregivers, and health care professionals (HCP) believe current therapy practices are insufficient, specifically calling out the upper extremity as an area where innovation is needed to develop highly usable prosthetics/orthotics for the stroke population. A promising method for controlling upper extremity technologies is to infer movement intention non-invasively from surface electromyography (EMG). However, existing technologies are often limited to research settings and struggle to meet user needs.

Approach

To address these limitations, we have developed the NeuroLife® EMG System, an investigational device which consists of a wearable forearm sleeve with 150 embedded electrodes and associated hardware and software to record and decode surface EMG. Here, we demonstrate accurate decoding of 12 functional hand, wrist, and forearm movements in chronic stroke survivors, including multiple types of grasps from participants with varying levels of impairment. We also collected usability data to assess how the system meets user needs to inform future design considerations.

Main results

Our decoding algorithm trained on historical- and within-session data produced an overall accuracy of 77.1 ± 5.6% across 12 movements and rest in stroke participants. For individuals with severe hand impairment, we demonstrate the ability to decode a subset of two fundamental movements and rest at 85.4 ± 6.4% accuracy. In online scenarios, two stroke survivors achieved 91.34 ± 1.53% across three movements and rest, highlighting the potential as a control mechanism for assistive technologies. Feedback from stroke survivors who tested the system indicates that the sleeve’s design meets various user needs, including being comfortable, portable, and lightweight. The sleeve is in a form factor such that it can be used at home without an expert technician and can be worn for multiple hours without discomfort.

Significance

The NeuroLife EMG System represents a platform technology to record and decode high-resolution EMG for the real-time control of assistive devices in a form factor designed to meet user needs. The NeuroLife EMG System is currently limited by U.S. federal law to investigational use.
Upper limb intention tremor assessment: opportunities and challenges in wearable technology
Authors: Paredes-Acuna Natalia , Utpadel-Fischler Daniel , Ding Keqin , Thakor Nitish V. , Cheng Gordon
Published: January 2024

Background

Tremors are involuntary rhythmic movements commonly present in neurological diseases such as Parkinson's disease, essential tremor, and multiple sclerosis. Intention tremor is a subtype associated with lesions in the cerebellum and its connected pathways, and it is a common symptom in diseases associated with cerebellar pathology. While clinicians traditionally use tests to identify tremor type and severity, recent advancements in wearable technology have provided quantifiable ways to measure movement and tremor using motion capture systems, app-based tasks and tools, and physiology-based measurements. However, quantifying intention tremor remains challenging due to its changing nature.

Methodology & Results

This review examines the current state of upper limb tremor assessment technology and discusses potential directions to further develop new and existing algorithms and sensors to better quantify tremor, specifically intention tremor. A comprehensive search using PubMed and Scopus was performed using keywords related to technologies for tremor assessment. Afterward, screened results were filtered for relevance and eligibility and further classified into technology type. A total of 243 publications were selected for this review and classified according to their type: body function level: movement-based, activity level: task and tool-based, and physiology-based. Furthermore, each publication's methods, purpose, and technology are summarized in the appendix table.

Conclusions

Our survey suggests a need for more targeted tasks to evaluate intention tremors, including digitized tasks related to intentional movements, neurological and physiological measurements targeting the cerebellum and its pathways, and signal processing techniques that differentiate voluntary from involuntary movement in motion capture systems.
Behavioral characterization of early nicotine withdrawal in the mouse: a potential model of acute dependence
Authors: Kim Baeksun , Im Heh-In
Published: January 2024

Background

Clinical and preclinical research have demonstrated that short-term exposure to nicotine during the initial experimentation stage can lead to early manifestation of withdrawal-like signs, indicating the state of “acute dependence”. As drug withdrawal is a major factor driving the progression toward regular drug intake, characterizing and understanding the features of early nicotine withdrawal may be important for the prevention and treatment of drug addiction. In this study, we corroborate the previous studies by showing that withdrawal-like signs can be precipitated after short-term nicotine exposure in mice, providing a potential animal model of acute dependence on nicotine.

Results

To model nicotine exposure from light tobacco use during the initial experimentation stage, mice were treated with 0.5 mg/kg (-)-nicotine ditartrate once daily for 3 days. On the following day, the behavioral tests were conducted after implementing spontaneous or mecamylamine-precipitated withdrawal. In the open field test, precipitated nicotine withdrawal reduced locomotor activity and time spent in the center zone. In the elevated plus maze test, the mecamylamine challenge increased the time spent in the closed arm and reduced the number of entries irrespective of nicotine experience. In the examination of the somatic aspect, precipitated nicotine withdrawal enhanced the number of somatic signs. Finally, nicotine withdrawal did not affect cognitive functioning or social behavior in the passive avoidance, spatial object recognition, or social interaction test.

Conclusions

Collectively, our data demonstrate that early nicotine withdrawal-like signs could be precipitated by the nicotinic antagonist mecamylamine in mice, and that early withdrawal from nicotine primarily causes physical symptoms.
Correlation analysis of risk factors for cervical lymphatic metastasis in papillary thyroid carcinoma
Authors: Sun Haoying , Zhao Xueyu , Wang Xin , Ma Jinzhu , Liu Ming
Published: January 2024

Objective

This study aims to identify and analyze the risk factors associated with Cervical Lymph Node Metastasis (CNM) in Papillary Thyroid Carcinoma (PTC) patients.

Methods

We conducted a retrospective study involving the clinicopathological data of 2384 PTC patients admitted to our hospital between January 2016 and December 2020. All relevant data were statistically processed and analyzed.

Results

The related risk factors for Central Lymph Node Metastasis (CLNM) were gender (male), age (≤ 30 years old), tumor lesion size (> 0.855 cm), and multifocal tumor foci. The ROC curve revealed that the critical value for predicting CLNM based on tumor lesion size was 0.855 (sensitivity = 57.9%, specificity = 69%, AUC = 0.269, and P < 0.05). Lateral Lymph Node Metastasis (LLNM) was positively correlated with tumor diameter. Specifically, the LLNM rate increased with the tumor diameter. LLNM occurrence was significantly higher in zones II, III, and IV than in zones I and V. Although the BRAF gene mutation detection assay has certain clinical benefits in diagnosing PTC and LLNM, no statistically significant difference was found in its relationship with central and lateral neck lymph node metastases (P = 0.741).

Conclusion

Our findings revealed that CLNM is associated with gender (male), age (≤ 30 years old), tumor lesion size (> 0.855 cm), and multiple tumor lesions in PTC patients. Central Lymph Node Dissection (CLND) is recommended for patients with these risk factors. On the other hand, preoperative ultrasound examination, fine-needle pathological examination, and genetic testing should be used to determine whether Lateral Cervical Lymph Node Dissection (LLND) is needed.
Exploring genetic variability under extended photoperiod in lentil (Lens Culinaris Medik): vegetative and phenological differentiation according to genetic material’s origins
Authors: Mitache Mohammed , Baidani Aziz , Bencharki Bouchaib , Idrissi Omar
Published: January 2024

Lentil is an important pulse that contributes to global food security and the sustainability of farming systems. Hence, it is important to increase the production of this crop, especially in the context of climate changes through plant breeding aiming at the development of high-yielding and climate-smart cultivars. However, conventional plant breeding approaches are time and resources consuming. Thus, speed breeding techniques enabling rapid generation turnover could help to accelerate the development of new varieties. The application of extended photoperiod prolonging the duration of the plant’s exposure to light and shortening the duration of the dark phase is among the simplest speed breeding techniques. In this study, genetic variability response under extended photoperiod (22 h of light/2 h of dark at 25 °C) of a lentil collection of 80 landraces from diverse latitudinal origins low (0°–20°), medium (21°–40°) and high (41°–60°), was investigated. Significant genetic variations were observed between accessions, for time to flowering [40 → 120 days], time of pods set [45 → 130 days], time to maturity [64 → 150 days], harvest index [0 → 0.24], green canopy cover [0.39 → 5.62], seedling vigor [2 → 5], vegetative stage length [40 → 120 days], reproduction stage length [3 → 13 days], and seed filing stage length [6 → 25 days]. Overall, the accessions from Low latitudinal origin demonstrated a favorable response to the extended photoperiod application with almost all accessions flowered, while 18% and 57% of accessions originating from medium and high latitudinal areas, respectively, did not successfully reach the flowering stage. These results enhanced our understanding lentil responses to photoperiodism under controlled conditions and are expected to play important roles in speed breeding based on the application of the described protocol for lentil breeding programs in terms of choosing appropriate initial treatments such as vernalization depending on the origin of accession.
A meta-analysis and trial sequential analysis comparing nonoperative versus operative management for uncomplicated appendicitis: a focus on randomized controlled trials
Authors: Brucchi Francesco , Bracchetti Greta , Fugazzola Paola , Viganò Jacopo , Filisetti Claudia , Ansaloni Luca , Dal Mas Francesca , Cobianchi Lorenzo , Danelli Piergiorgio
Published: January 2024

Background

The aim of this study is to provide a meta-analysis of randomized controlled trials (RCT) comparing conservative and surgical treatment in a population of adults with uncomplicated acute appendicitis.

Methods

A systematic literature review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search was conducted in MEDLINE, Embase, and CENTRAL. We have exclusively incorporated randomized controlled trials (RCTs). Studies involving participants with complicated appendicitis or children were excluded. The variables considered are as follows: treatment complications, complication-free treatment success at index admission and at 1 year follow-up, length of hospital stay (LOS), quality of life (QoL) and costs.

Results

Eight RCTs involving 3213 participants (1615 antibiotics/1598 appendectomy) were included. There was no significant difference between the two treatments in terms of complication rates (RR = 0.66; 95% CI 0.61—1.04, P = 0.07, I2 = 69%). Antibiotics had a reduced treatment efficacy compared with appendectomy (RR = 0.80; 95% CI 0.71 to 0.90, p < 0.00001, I2 = 87%) and at 1 year was successful in 540 out of 837 (64.6%, RR = 0.69, 95% confidence interval 0.61 to 0.77, p < 0.00001, I2 = 81%) participants. There was no difference in LOS (mean difference − 0.58 days 95% confidence interval − 1.59 to 0.43, p = 0.26, I2 = 99%). The trial sequential analysis has revealed that, concerning the three primary outcomes, it is improbable that forthcoming RCTs will significantly alter the existing body of evidence.

Conclusions

As further large-scale trials have been conducted, antibiotic therapy proved to be safe, less expensive, but also less effective than surgical treatment. In order to ensure well-informed decisions, further research is needed to explore patient preferences and quality of life outcomes.
Circ_0000376 regulates miR-577/HK2/LDHA signaling pathway to promote the growth, invasion and glycolysis of osteosarcoma
Authors: Dai Hongchun , Yi Guangming , Jiang Dong , Min Yanmei , Li Zongwei
Published: January 2024

Background

Many studies have confirmed that circular RNAs (circRNAs) mediate the malignant progression of various tumors including osteosarcoma (OS). Our study is to uncover novel molecular mechanisms by which circ_0000376 regulates OS progression.

Methods

The expression of circ_0000376, microRNA (miR)-577, hexokinase 2 (HK2) and lactate dehydrogenase-A (LDHA) was determined by quantitative real-time PCR. OS cell proliferation, apoptosis and invasion were measured using cell counting kit 8 assay, colony formation assay, EdU assay, flow cytometry and transwell assay. Besides, cell glycolysis was assessed by testing glucose consumption, lactate production, and ATP/ADP ratios. Protein expression was examined by western blot analysis. The interaction between miR-577 and circ_0000376 or HK2/LADA was verified by dual-luciferase reporter assay. The role of circ_0000376 on OS tumor growth was explored by constructing mice xenograft models.

Results

Circ_0000376 had been found to be upregulated in OS tissues and cells. Functional experiments revealed that circ_0000376 interference hindered OS cell growth, invasion and glycolysis. Circ_0000376 sponged miR-577 to reduce its expression. In rescue experiments, miR-577 inhibitor abolished the regulation of circ_0000376 knockdown on OS cell functions. MiR-577 could target HK2 and LDHA in OS cells. MiR-577 suppressed OS cell growth, invasion and glycolysis, and these effects were reversed by HK2 and LDHA overexpression. Also, HK2 and LDHA expression could be regulated by circ_0000376. In vivo experiments showed that circ_0000376 knockdown inhibited OS tumorigenesis.

Conclusion

Circ_0000376 contributed to OS growth, invasion and glycolysis depending on the regulation of miR-577/HK2/LDHA axis, providing a potential target for OS treatment.

Graphical Abstract
Effect of different loads on facet joint motion during lumbar lateral bending in sitting position
Authors: Han Ye , Yuan Wei , Sun Shaosong , Ren Bao , Zhang Xiong , Li Zheng , Miao Jun , Wang Xiaodong
Published: January 2024

Objective

To study the effect of weight-bearing on lumbar facet joint during lateral bending in sitting position.

Methods

Ten normal healthy people (5 males and 5 females) aged 25–39 years (mean 32 ± 4.29 years) were recruited. CT scanning was used to reconstruct the lumbar spine model, and then dual fluoroscopic image system (DFIS) was used to restore the lumbar facet joint movement in sitting position. Finally, the lumbar facet joint translation distance and rotation angle were measured.

Results

In L3-4 level, the displacement of right facet joint in Y-axis was the smallest at 0.05 ± 0.40 mm, the displacement of 0 kg left facet joint in X-axis was the largest at 1.68 ± 0.85 mm, and the rotation angle was − 0.57 ± 1.43° to 5.66 ± 2.70° at 10 kg; in L4-5 level, the displacement of right facet joint in Y-axis was the smallest at 10 kg, − 0.13 ± 0.91 mm, and the displacement of left facet joint in Z-axis was the largest at − 2.11 ± 0.88 mm, and the rotation angle was 0.21 ± 2.14° to 7.89 ± 2.59° at 10 kg; in L5-S1 level, the displacement of right facet joint in Y-axis was the smallest at 10 kg, − 0.17 ± 1.10 mm, and the displacement of 0 kg left facet joint in X-axis was the largest at 2.19 ± 2.28 mm, and the rotation angle was 0.03 ± 2.02° to 3.98 ± 0.37°.

Conclusion

In sitting position, weight-bearing has certain influence on the displacement of facet joints during lumbar lateral bending movement, and this influence occurs simultaneously in translation and rotation; the left and right facet joints are not symmetrical during lumbar lateral bending movement.
Efficacy and safety of continuous passive motion and physical therapy in recovery from knee arthroplasty: a systematic review and meta-analysis
Authors: Jia Zhengfeng , Zhang Yan , Zhang Wupeng , Xu Cheng , Liu Wanheng
Published: January 2024

Background

Continuous passive motion (CPM) is commonly used as a postoperative rehabilitation treatment, along with physical therapy, for postoperative knee rehabilitation. However, the comparison between the two in terms of efficacy in postoperative knee replacement recovery is unclear.

Purpose

To compare efficacy and safety of combined CPM versus physical therapy alone in postoperative rehabilitation after knee arthroplasty.

Methods

PubMed, Embase, and Web of Science databases were used to retrieve and access clinical studies on the efficacy of CPM compared with physical therapy. Review Manager software was used for study publication bias assessment and data analysis based on inclusion criteria.

Results

A total of 6 articles covering 557 patients were included in the study. In terms of range of motion (ROM), passive knee flexion was similar between CPM and physical therapy (PT) (WMD, − 0.17; 95% CI,  − 0.98–0.64; p = 0.68). At long-term follow-up, passive knee extension was similar between CPM and physical therapy (PT) (WMD,  − 0.28; 95% CI,  − 1.47 to  − 0.92; I2 = 65%, p =0.65). In addition, CPM generates significantly higher in length of stay (WMD, 0.50; 95% CI,  − 0.31 to 0.69; I2 = 3%, p < 0.001). CPM generates significantly higher treatment costs and incurs more care costs relative to physical therapy.

Conclusion

Compared to PT, combined with CPM failed to significantly improve ROM of the knees and patient’s satisfaction. In addition, CPM treatment significantly increased the cost of hospitalization.
Percutaneous endoscopic transforaminal vs. interlaminar discectomy for L5–S1 lumbar disc herniation: a retrospective propensity score matching study
Authors: Li Tusheng , Yang Guangnan , Zhong Wei , Liu Jiang , Ding Zhili , Ding Yu
Published: January 2024

Objective

Percutaneous endoscopic lumbar discectomy (PELD) is a safe and effective minimally invasive surgery for treating lumbar disc herniation (LDH); however, the comparative clinical efficacy of percutaneous endoscopic transforaminal discectomy (PETD) and percutaneous endoscopic interlaminar discectomy (PEID) in treating L5–S1 LDH remains unclear. This study compared the clinical advantages of PEID and PETD for treating L5–S1 LDH.

Methods

This was a single-centre retrospective study analysing clinical data from 120 patients with L5–S1 LDH between February 2016 and May 2020. Propensity score matching (PSM) was used to adjust for imbalanced confounding variables between the two groups. Perioperative data were recorded, and clinical outcomes, including functional scores and imaging data, were compared between groups. Functional scores included visual analogue scale (VAS) for back and leg pain, Oswestry disability index (ODI), and modified MacNab criteria. Imaging data included disc height index (DHI), ratio of greyscale (RVG), and range of motion (ROM) of the responsible segment.

Results

After PSM, 78 patients were included in the study, and all covariates were well balanced between the two groups. In the matched patients, the PEID group showed significantly shorter surgical time (65.41 ± 5.05 vs. 84.08 ± 5.12 min) and lower frequency of fluoroscopy (2.93 ± 0.63 vs. 11.56 ± 1.54) compared with the PETD group (P < 0.001). There were no statistically significant differences in intraoperative blood loss, postoperative hospital stay, total incision length, and incidence of complications between the two groups (P > 0.05). After surgery, both groups showed significant improvement in back and leg pain based on VAS and ODI scores (P < 0.05). There were no statistically significant differences in clinical functional scores and imaging data between the two groups at various time points after surgery (P > 0.05). According to the modified MacNab criteria, the excellent and good rates in the PEID group and PETD group were 91.89% and 89.19%, respectively, with no statistically significant difference (P > 0.05).

Conclusion

PEID and PETD have similar clinical efficacy in treating L5–S1 disc herniation. However, PEID is superior to PETD in reducing operation time and frequency of fluoroscopy.
Inhibition of LINC00958 hinders the progression of osteoarthritis through regulation of the miR-214-3p/FOXM1 axis
Authors: Yin Yingchuan , He Qiaojuan , He Jing , Feng Ying , Xu Yunyun
Published: January 2024

Objective

We investigated the impact of the long noncoding RNA LINC00958 on cellular activity and oxidative stress in osteoarthritis (OA).

Methods

We performed bioinformatics analysis via StarBase and luciferase reporter assays to predict and validate the interactions between LINC00958 and miR-214-3p and between miR-214-3p and FOXM1. The expression levels of LINC00958, miR-214-3p, and FOXM1 were measured by qRT-PCR and western blotting. To assess effects on CHON-001 cells, we performed MTT proliferation assays, evaluated cytotoxicity with a lactate dehydrogenase (LDH) assay, and examined apoptosis through flow cytometry. Additionally, we measured the levels of apoptosis-related proteins, including BAX and BCL2, using western blotting. The secretion of inflammatory cytokines (IL-6, IL-8, and TNF-α) was measured using ELISA.

Results

Our findings confirmed that LINC00958 is a direct target of miR-214-3p. LINC00958 expression was upregulated but miR-214-3p expression was downregulated in both OA cells and IL-1β-stimulated CHON-001 cells compared to the corresponding control cells. Remarkably, miR-214-3p expression was further reduced after miR-214-3p inhibitor treatment but increased following LINC00958-siRNA stimulation. Silencing LINC00958 significantly decreased its expression, and this effect was reversed by miR-214-3p inhibitor treatment. Notably, LINC00958-siRNA transfection alleviated the IL-1β-induced inflammatory response, as evidenced by the increased cell viability, reduced LDH release, suppression of apoptosis, downregulated BAX expression, and elevated BCL2 levels. Moreover, LINC00958 silencing led to reduced secretion of inflammatory factors from IL-1β-stimulated CHON-001 cells. The opposite results were observed in the miR-214-3p inhibitor-transfected groups. Furthermore, in CHON-001 cells, miR-214-3p directly targeted FOXM1 and negatively regulated its expression.

Conclusion

Our findings suggest that downregulating LINC00958 mitigates IL-1β-induced injury in CHON-001 cells through the miR-214-3p/FOXM1 axis. These results imply that LINC00958 plays a role in OA development and may be a valuable therapeutic target for OA.
Regulation of polysaccharide in Wu‐tou decoction on intestinal microflora and pharmacokinetics of small molecular compounds in AIA rats
Authors: Yang Di , Cheng Xiaoxu , Fan Meiling , Xie Dong , Liu Zhiqiang , Zheng Fei , Dai Yulin , Pi Zifeng , Yue Hao
Published: January 2024

Wu-tou decoction (WTD), a traditional Chinese medicine prescription, is used to treat rheumatoid arthritis (RA). It works by controlling intestinal flora and its metabolites, which in turn modulates the inflammatory response and intestinal barrier function. Small molecular compounds (SM) and polysaccharides (PS) were the primary constituents of WTD extract. In this work, a model of adjuvant-induced arthritis (AIA) in rats was established and treated with WTD, SM, and PS, respectively. 16S rRNA gene sequencing was used to examine the regulatory impact of the various groups on the disturbance of the gut flora induced by RA. Further, since PS cannot be absorbed into the blood, the influence of PS on the absorption and metabolism of SM was studied by examining their pharmacokinetic (PK) parameters of 23 active components in SM by UPLC-MS/MS. WTD was found to be more effective than PS and SM in alleviating arthritis in AIA rats, which may be related to changes in gut flora. The PK properties of 13 active compounds were altered after PS intervene. Based on the findings, PS may be able to manage the disruption of intestinal microbiota, enhance the intestinal environment of model animals, and hence influence SM absorption and metabolism.
The impact of the COVID-19 pandemic on rates of adolescents receiving psychopharmacological medication in Austria
Authors: Otter M. , Kothgassner O. D. , Lepuschütz L. , Drahos S. , Plener P. L.
Published: January 2024

Background

The COVID-19 pandemic has impacted many aspects of everyday life, including the (mental) healthcare system. An increase in depression and anxiety symptoms has been reported worldwide, and is particularly pronounced in females and young people. We aimed to evaluate changes in prescription rates for psychopharmacological medication, which is often used to treat depression and anxiety.

Method

Based on data from the Austrian public health insurance institutions, we conducted an interrupted time series analysis of antidepressants and antipsychotics, comparing prescription rate developments before and throughout the COVID-19 pandemic (2013 to 2021), with a special focus on adolescents (10–19 years) in comparison to the general population. Data were based on all public prescriptions in the outpatient sector nationwide. Age- and sex-stratified time-series models were fitted to the pre-COVID period (first quarter (Q1) of 2013 to second quarter (Q2) of 2020). These were used to generate forecasts for the period from the third quarter (Q3) of 2020 to the fourth quarter (Q4) of 2021, which were subsequently compared to observed developments in order to assess significant deviations from the forecasted development paths.

Results

For the majority of the evaluated period, we found a significant excess of antidepressant prescriptions among both male and female adolescents (10–14 and 15–19 years) compared to the forecasted development path, while the general population was mostly within 97.5% confidence intervals of the forecasts. Regarding antipsychotics, the interrupted time series analysis revealed a significant excess in the group of female adolescents in almost all quarters, which was especially pronounced in the 15–19 age group. Prescription rates of antipsychotics in the general population only showed a significant excess in two quarters.

Conclusion

Increased rates of adolescents receiving psychopharmacological treatment echo the epidemiological trends of an increase in depression and anxiety symptoms reported in the literature. This increase is especially pronounced in female adolescents.
Initial treatment with a single capsule containing half-dose quadruple therapy versus standard-dose dual therapy in hypertensive patients (QUADUAL): statistical analysis plan for a randomized, blinded, crossover trial
Authors: Zhao Xiexiong , Li Xingli , Liu Tao , Yang Guoping , Chen Ye , Huang Miao , Zhao Lin , Li Xiaogang , Jiang Weihong
Published: January 2024

Background

Combined antihypertensive therapy has obvious advantages over single drug therapy. Hypertension guidelines fully affirm the efficacy of dual combination in initial antihypertensive therapy. Recent studies have also pointed out that the quadruple combination of very low-dose antihypertensive drugs is superior to single drugs. However, whether low-dose quadruple therapy is better than dual combination is unknown.

Methods/design

A randomized double-blind crossover clinical trial will be conducted to compare the efficacy and safety of low-dose quadruple antihypertensives (irbesartan 75 mg + metoprolol 23.75 mg + amlodipine 2.5 mg + indapamide 1.25 mg) with standard-dose dual antihypertensives (irbesartan 150 mg + amlodipine 5 mg) in the initial treatment of patients with mild to moderate hypertension (140–179/90–109 mmHg). Ninety patients are required and will be recruited and randomly assigned in a 1:1 ratio to two crossover groups. Two groups will receive a different combination therapy for 4 weeks, then switch to the other combination therapy for 4 weeks, with a 2-week wash-out. Antihypertensive effects and related adverse effects of the two antihypertensive combination treatments will be compared. The primary outcome, i.e., mean 24-h systolic blood pressure in ambulatory blood pressure monitoring, will be assessed via linear mixed-effects model.

Discussion

This statistical analysis plan will be confirmed prior to blind review and data lock before un-blinding and is sought to increase the validity of the QUADUAL trial.

Trial registration

ClinicalTrials.gov, NCT05377203. Registered May 11, 2022, https://clinicaltrials.gov/study/NCT05377203.
Active versus sham DLPFC-NAc rTMS for depressed adolescents with anhedonia using resting-state functional magnetic resonance imaging (fMRI): a study protocol for a randomized placebo-controlled trial
Authors: Lv Runxin , Cai Min , Tang Nailong , Shi Yifan , Zhang Yuyu , Liu Nian , Han Tianle , Zhang Yaochi , Wang Huaning
Published: January 2024

Background

Anhedonia, which is defined as the inability to feel pleasure, is considered a core symptom of major depressive disorder (MDD). It can lead to several adverse outcomes in adolescents, including heightened disease severity, resistance to antidepressants, recurrence of MDD, and even suicide. Specifically, patients who suffer from anhedonia may exhibit a limited response to selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT). Previous researches have revealed a link between anhedonia and abnormalities within the reward circuitry, making the nucleus accumbens (NAc) a potential target for treatment. However, since the NAc is deep within the brain, repetitive transcranial magnetic stimulation (rTMS) has the potential to modulate this specific region. Recent advances have enabled treatment technology to precisely target the left dorsolateral prefrontal cortex (DLPFC) and modify the functional connectivity (FC) between DLPFC and NAc in adolescent patients with anhedonia. Therefore, we plan to conduct a study to explore the safety and effectiveness of using resting-state functional connectivity magnetic resonance imaging (fcMRI)-guided rTMS to alleviate anhedonia in adolescents diagnosed with MDD.

Methods

The aim of this article is to provide a study protocol for a parallel-group randomized, double-blind, placebo-controlled experiment. The study will involve 88 participants who will be randomly assigned to receive either active rTMS or sham rTMS. The primary object is to measure the percentage change in the severity of anhedonia, using the Snaith-Hamilton Pleasure Scale (SHAPS). The assessment will be conducted from the baseline to 8-week post-treatment period. The secondary outcome includes encompassing fMRI measurements, scores on the 17-item Hamilton Rating Scale for Depression (HAMD-17), the Montgomery Asberg Depression Rating Scale (MADRS), the Chinese Version of Temporal Experience of Pleasure Scale (CV-TEPS), and the Chinese Version of Beck Scale for Suicide Ideation (BSI-CV). The Clinical Global Impression (CGI) scores will also be taken into account, and adverse events will be monitored. These evaluations will be conducted at baseline, as well as at 1, 2, 4, and 8 weeks.

Discussion

If the hypothesis of the current study is confirmed, (fcMRI)-guided rTMS could be a powerful tool to alleviate the core symptoms of MDD and provide essential data to explore the mechanism of anhedonia.

Trial registration

ClinicalTrials.gov NCT05544071. Registered on 16 September 2022.