bluuebunny/crossref_metadata_2025 huggingface dataset:
Substance Use Treatment Utilization Among Individuals With Substance Use Disorders in the United States During the COVID-19 Pandemic: Findings on the Role of Polysubstance Use, Criminal Justice Involvement, and Mental Illness From the National Survey on Drug Use and Health
Authors: Apsley Hannah B. , Santos-Lozada Alexis R. , Gray Joy , Hard Gregory , Jones Abenaa A.
Published: June 2024

This study used the National Survey on Drug Use and Health to assess a nationally representative sample (N = 4596) weighted to represent 35.2 million adults with DSM-5 criteria-determined substance use disorders (SUDs). This study explored substance use treatment utilization in 2020, emphasizing populations with high vulnerability (e.g., criminal justice involvement (CJI) through parole or probation, polysubstance use, severe mental illness, and HIV/STI). Substance use treatment was broadly defined (any inpatient, outpatient/doctor’s office, self-help/other for alcohol/drugs). Our results indicated that among adults with SUDs in 2020, 7 million (20%) had multiple SUDs, 1.75 million (5%) had CJI, 5.3 million (15%) had a severe mental illness, and 1.8 million (5%) had a diagnosis of HIV/STI in the last year. Only 7% of individuals with SUD sought any substance use treatment in the past year. CJI (aOR: 13.39, 95% CI: [7.82, 22.94]), serious mental illness (aOR: 3.27, 95% CI: [1.93, 5.55]), and having both 2 (aOR: 2.10, 95% CI: [1.29, 3.42]) or 3 or more SUDs (aOR: 3.46, 95% CI: [1.82, 6.58]) were all associated with a greater likelihood of receiving treatment. Marriage (aOR: 0.43, 95% CI: [0.25, 0.74]) and having an income twice the poverty threshold (aOR: 0.53, 95% CI: [0.29, 0.94]) were associated with reduced odds of receiving any substance use treatment. Compared to those 18 to 25, older individuals had increased odds (2-4 times) of receiving treatment. Interventions are crucially needed to increase access to treatment among those with SUDs.
Adjudicating Equity in Music Performance Assessments: A Literature Review
Authors: Kaufman Brian , Kladder Jonathan , Palmer Elizabeth S.
Published: June 2024

Music performance assessments (MPAs), also known as festivals, adjudications, or contests, are a yearly part of the music education experience for many teachers and students in school bands, orchestras, and choirs. A brief history outlining the origins and purposes of MPA is shared. Issues of equity in modern-day MPA are then explored, including the reliability and validity of adjudication instruments; adjudicator bias and evaluation forms; limitations of music lists and musical approaches allowed; and inequities related to gender, socioeconomic status, social class, and race. Challenges to classroom practice and teacher evaluation are discussed—including the potential disconnect between MPA and 21st century educational values. Implications for music teachers, music teacher educators, festival organizers, and music education association leaders are discussed.
Could cough hypersensitivity symptom profile differentiate phenotypes of chronic cough?
Authors: Kim Mi-Yeong , Won Ha-Kyeong , Oh Ji-Yoon , Lee Ji-Hyang , Jo Eun-Jung , Kang Sung-Yoon , Lee Ji-Ho , Lee Seung-Eun , Kang Noeul , Kim Young-Chan , Lee Hwa Young , An Jin , Yoo Youngsang , Shim Ji-Su , Park So-Young , Park Han-Ki , Kim Min-Hye , Kim Sae-Hoon , Kim Sang-Heon , Chang Yoon-Seok , Kim Sang-Hoon , Lee Byung-Jae , Birring Surinder S. , Song Woo-Jung
Published: June 2024

Background

Recently, cough reflex hypersensitivity has been proposed as a common underlying feature of chronic cough in adults. However, symptoms and clinical characteristics of cough hypersensitivity have not been studied amongst phenotypes of chronic cough. This study aimed to compare symptom features, such as cough triggers and associated throat sensations, of cough hypersensitivity in patients with asthmatic chronic cough and those with refractory chronic cough (RCC).

Methods

Patients with chronic cough from the Korean Chronic Cough Registry were prospectively evaluated over 6 months. Physicians determined the aetiological diagnosis based on clinical evaluations and responses to treatment at the 6-month follow-up visit. Symptoms of cough hypersensitivity and cough-specific quality of life were assessed using the Cough Hypersensitivity Questionnaire (CHQ) and the Leicester Cough Questionnaire (LCQ), respectively.

Results

The analysis included 280 patients who completed the follow-up: 79 with asthmatic cough (cough variant asthma or eosinophilic bronchitis) and 201 with RCC. Baseline CHQ scores were similar between the groups (8.3±3.7 in asthmatic coughversus8.9±3.9 in RCC; p=0.215, adjusted for age, sex and LCQ score). There were no significant between-group differences in the LCQ and cough severity Visual Analog Scale scores. Both groups showed a similar negative correlation with LCQ scores (asthmatic cough: r=−0.427, p<0.001; RCC: r=−0.306, p<0.001).

Conclusions

The symptoms of cough hypersensitivity may not distinguish between asthmatic cough and RCC. This suggests that chronic cough is the primary diagnosis in both phenotypes. It indicates a shared mechanism in their cough pathogenesis, despite having potentially different treatable traits.
Direct profiling of breast cancer-derived extracellular vesicles using Pd-perovskite electrochemical biosensing platform
Authors: Dezhakam Ehsan , Khalilzadeh Balal , Naseri Abdolhossein , Rahbarghazi Reza , Mahmoudi Elham , Niaei Aligholi , Mahdipour Mahdi , Mardi Narges , Isildak Ibrahim
Published: June 2024

Extracellular vesicles (EVs) harbor several signaling molecules to maintain intercellular communication. Based on the exosomal cargo type, metabolic, genomic, and proteomic status of parent cells can be investigated. Due to the existence of trivial levels of target molecules inside EVs, the application of accurate and sensitive detection methods is mandatory. Here, we used an electrochemical immunosensor using a biotinylated monoclonal CD63 antibody as the capturing element for the detection of EVs isolated from MDA-MB-231 cells and cancer patients. Simultaneously, breast cancer biomarker CA-15-3 was detected in isolated EVs using a sandwich method to increase specificity. Data indicated a linear dynamic range of 2000–10000 EVs/µL and a lower limit of quantification of 2000 EVs/µL. Based on data from real sample analysis, the levels of exosomal CA-15-3 can differ according to the severity and systemic content of this factor. Pd-perovskite-based immunosensor provides a platform for quick and in-depth analysis of EVs isolated for cancer cells.
PyMulSim: a method for computing node similarities between multilayer networks via graph isomorphism networks
Authors: Cinaglia Pietro
Published: June 2024

Background

In bioinformatics, interactions are modelled as networks, based on graph models. Generally, these support a single-layer structure which incorporates a specific entity (i.e., node) and only one type of link (i.e., edge). However, real-world biological systems consisting of biological objects belonging to heterogeneous entities, and these operate and influence each other in multiple contexts, simultaneously. Usually, node similarities are investigated to assess the relatedness between biological objects in a network of interest, and node embeddings are widely used for studying novel interaction from a topological point of view. About that, the state-of-the-art presents several methods for evaluating the node similarity inside a given network, but methodologies able to evaluate similarities between pairs of nodes belonging to different networks are missing. The latter are crucial for studies that relate different biological networks, e.g., for Network Alignment or to evaluate the possible evolution of the interactions of a little-known network on the basis of a well-known one. Existing methods are ineffective in evaluating nodes outside their structure, even more so in the context of multilayer networks, in which the topic still exploits approaches adapted from static networks. In this paper, we presentedpyMulSim, a novel method for computing the pairwise similarities between nodes belonging to different multilayer networks. It uses a Graph Isomorphism Network (GIN) for the representative learning of node features, that uses for processing the embeddings and computing the similarities between the pairs of nodes of different multilayer networks.

Results

Our experimentation investigated the performance of our method. Results show that our method effectively evaluates the similarities between the biological objects of a source multilayer network to a target one, based on the analysis of the node embeddings. Results have been also assessed for different noise levels, also through statistical significance analyses properly performed for this purpose.

Conclusions

PyMulSimis a novel method for computing the pairwise similarities between nodes belonging to different multilayer networks, by using a GIN for learning node embeddings. It has been evaluated both in terms of performance and validity, reporting a high degree of reliability.
Comparison of 96-kV and 120-kV cone-beam CT for the assessment of cochlear implants
Authors: Burck Iris , Yel Ibrahim , Martin Simon , Albrecht Moritz H. , Koch Vitali , Booz Christian , Pinto dos Santos Daniel , Kaltenbach Benjamin , Ackermann Hanns , Koivisto Juha , Helbig Silke , Stöver Timo , Vogl Thomas J. , Scholtz Jan-Erik
Published: June 2024

Background

To compare the diagnostic value of 120-kV with conventional 96-kV Cone-Beam CT (CBCT) of the temporal bone after cochlear implant (CI) surgery.

Methods

This retrospective study included CBCT scans after CI surgery between 06/17 and 01/18. CBCT allowed examinations with 96-kV or 120-kV; other parameters were the same. Two radiologists independently evaluated following criteria on 5-point Likert scales: osseous spiral lamina, inner and outer cochlear wall, semi-circular canals, mastoid trabecular structure, overall image quality, metal and motion artefacts, depiction of intracochlear electrode position and visualisation of single electrode contacts. Effective radiation dose was assessed.

Results

Seventy-five patients (females, n = 39 [52.0%], mean age, 55.8 ± 16.5 years) were scanned with 96-kV (n = 32, 42.7%) and 120-kV (n = 43, 57.3%) protocols including CI models from three vendors (vendor A n = 7; vendor B n = 43; vendor C n = 25). Overall image quality, depiction of anatomical structures, and electrode position were rated significantly better in 120-kV images compared to 96-kV (all p < = 0.018). Anatomical structures and electrode position were rated significantly better in 120-kV CBCT for CI models from vendor A and C, while 120-kV did not provide improved image quality in CI models from vendor B. Radiation doses were significantly higher for 120-kV scans compared to 96-kV (0.15 vs. 0.08 mSv, p < 0.001).

Conclusions

120-kV and 96-kV CBCT provide good diagnostic images for the postoperative CI evaluation. While 120-kV showed improved depiction of temporal bone and CI electrode position compared to 96-kV in most CI models, the 120-kV protocol should be chosen wisely due to a substantially higher radiation exposure.
Identifying the mechanism of polysaccharopeptide against breast cancer based on network pharmacology and experimental verification
Authors: Xu Cuixiang , Sun Lijun , Wang Huxia , Sun Jingying , Feng Yangmeng , Wang Xingguang , Song Zhangjun
Published: June 2024

Polysaccharopeptide (PSP) is a potential active component in traditional Chinese medicine because of its anticancer effects on a variety of cancer cells and as immune enhancers of the immune system. Previous studies on the role of PSP in breast cancer have been limited, and the mechanism has not been clarified. This study is based on network pharmacology and molecular docking technology to predict the possible target of PSP treatment of breast cancer, and use experiments to verify the effect and mechanism of PSP on breast cancer. In this study, 287 PSP targets were obtained using SwissTargetPrediction database and PharmMapper database, and 183 breast cancer targets were obtained using DisGenNET database. By intersections of PSP targets and breast cancer targets, a total of 10 intersections were obtained. GO functional enrichment, KEGG pathway enrichment and molecular docking of these 10 target genes were performed to obtain the potential targets of PSP on breast cancer. In vitro experiments, we found that PSP significantly inhibited the proliferation and induced apoptosis of breast cancer cell lines MDA-MB-231, SUM-159 and MCF-7. Western Blot results showed that PSP could down-regulate the expression of p-JAK2 and p-STAT3 proteins. Similarly, the results of in vivo experiments showed that PSP can directly inhibit the tumor of MDA-MB-231 tumor-bearing mice, and the mechanism of action is mainly to inhibit the JAK2-STAT3 pathway. The above results were consistent with the results of network pharmacology, which provides a scientific basis for the clinical application of PSP in breast cancer patients.
Notable dysthymia: evolving trends of major depressive disorders and dysthymia in China from 1990 to 2019, and projections until 2030
Authors: Wang Wei , Wang Yihe , Wang Feng , Chen Hui , Qin Xiaqing , Yang Lexia , Yang Xiaorong , Yang Lejin
Published: June 2024

Background

Depressive disorders have been identified as a significant contributor to non-fatal health loss in China. Among the various subtypes of depressive disorders, dysthymia is gaining attention due to its similarity in clinical severity and disability to major depressive disorders (MDD). However, national epidemiological data on the burden of disease and risk factors of MDD and dysthymia in China are scarce.

Methods

This study aimed to evaluate and compare the incidence, prevalence, and disability-adjusted life-years (DALYs) caused by MDD and dysthymia in China between 1990 and 2019. The temporal trends of the depressive disorder burden were evaluated using the average annual percentage change. The comparative risk assessment framework was used to estimate the proportion of DALYs attributed to risk factors, and a Bayesian age-period-cohort model was applied to project the burden of depressive disorders.

Results

From 1990 to 2019, the overall age-standardized estimates of dysthymia in China remained stable, while MDD showed a decreasing trend. Since 2006, the raw prevalence of dysthymia exceeded that of MDD for the first time, and increased alternately with MDD in recent years. Moreover, while the prevalence and burden of MDD decreased in younger age groups, it increased in the aged population. In contrast, the prevalence and burden of dysthymia remained stable across different ages. In females, 11.34% of the DALYs attributable to depressive disorders in 2019 in China were caused by intimate partner violence, which has increasingly become prominent among older women. From 2020 to 2030, the age-standardized incidence, prevalence, and DALYs of dysthymia in China are projected to remain stable, while MDD is expected to continue declining.

Conclusions

To reduce the burden of depressive disorders in China, more attention and targeted strategies are needed for dysthymia. It’s also urgent to control potential risk factors like intimate partner violence and develop intervention strategies for older women. These efforts are crucial for improving mental health outcomes in China.
Comparison of food intake pattern of diabetic patients and healthy individuals in a sample of Saudi population: a case-control study
Authors: Saaty Afnan H. , Aljadani Haya MA.
Published: June 2024

Background

There has been a significant rise in the number of individuals diagnosed with type 2 diabetes mellitus (T2DM), with the condition reaching epidemic proportions globally. This study examined the dietary pattern of a sample of Saudi Arabian adults with T2DM compared to control non-diabetics.

Methods

Data from 414 participants, 207 control and 207 T2DM was analyzed. Anthropometric measurements, foods intake such as vegetables, fruits, whole grains, fried foods, sweetened juice, sweets, and pastries consumption as well as physical activity were obtained by an interview-survey.

Results

The consumption of vegetables, green and leafy vegetables, starchy vegetables, fruits, proteins, and milk was significantly higher in the diabetics (p< 0.0001 for all and p<0.01 for starchy vegetables). Of the case group, 79.7% of them consumed whole-wheat bread while 54.6% of them consumed low fat milk (p<0.0001). There was a significant decrease in the percentage of cases who consumed discretionary foods and sweetened juices and soft drinks (24.1%), avoided sweets (75.8%) and pastries (37.1%), (p<0.0001). There were also significant increases in the percentages of participants who use healthy fat (as olive oil) in the case group (78.7%) (p<0.001). There was a significant increase in the percentage of diabetics who followed a diet to lose weight (15%) (p<0.05). The majority of the two study groups were physically inactive (control 95.2% & case 94.2%).

Conclusions

The results of this study provide insight on that diabetics generally follow a healthy diet, yet their engagement in physical activity may not be optimal.
Impact of the pandemic on leisure physical activity and alcohol consumption
Authors: Granström Fredrik , Wenemark Marika , Festin Karin , Good Elin , Frielingsdorf Helena , Lowén Mats , Rystedt Ingrid
Published: June 2024

Background

The COVID-19 pandemic precipitated heightened morbidity and elevated mortality attributed to the SARS-CoV-2 infection. The pandemic also influenced health behaviors such as physical activity (PA) and alcohol consumption. The aim of this study was to examine changes in leisure PA and alcohol consumption in Sweden during the pandemic, and elucidate potential discrepancies in changes across demographic strata and socioeconomic status (SES).

Methods

Data were retrieved from two waves of the longitudinal cohort study Life conditions, Stress and Health (LSH) (n = 2,523). Two measures of change were used; longitudinal change relative to baseline (2012–2015) and reported change compared to before the pandemic. For these two change measures, differences between sex, age group and SES were analyzed using multinomial logistic regression.

Results

Regardless of the change measure, the proportion of individuals with diminished PA was notably higher among females compared to males. Furthermore, relative to baseline, females were less likely to have increased their PA, however according to the reported change they were more likely to have increased PA. Longitudinal change in PA compared to baseline followed a reversed age gradient, while, according to reported change, a decrease in PA during the pandemic was most prevalent in respondents 45 years of age at baseline (OR = 1.8, CI: 1.2–2.5) and respondents 50 years of age at baseline (OR = 1.7, CI: 1.2–2.4). High SES was associated with a greater variability in PA. Alcohol consumption was generally reduced during the pandemic. However, individuals aged 40 or 45 years at baseline were more likely than others to have initiated risky alcohol consumption.

Conclusions

Females exhibited a greater propensity to alter their PA levels during the pandemic, with the most profound decreases observed among individuals of working ages. Despite a general downturn in alcohol consumption, individuals aged 40 and 45 had a heightened likelihood of having initiated risky alcohol consumption compared to individuals in other age cohorts. In conclusion, societal restrictions during a pandemic render a dual impact on PA levels. While posing a risk for decreased PA among individuals in working ages, the restrictions also present a potential window of opportunity to increase PA, particularly among females.
Surprising and novel multivariate sequential patterns using odds ratio for temporal evolution in healthcare
Authors: Casanova Isidoro J. , Campos Manuel , Juarez Jose M. , Gomariz Antonio , Canovas-Segura Bernardo , Lorente-Ros Marta , Lorente Jose A.
Published: June 2024

Background

Pattern mining techniques are helpful tools when extracting new knowledge in real practice, but the overwhelming number of patterns is still a limiting factor in the health-care domain. Current efforts concerning the definition of measures of interest for patterns are focused on reducing the number of patterns and quantifying their relevance (utility/usefulness). However, although the temporal dimension plays a key role in medical records, few efforts have been made to extract temporal knowledge about the patient’s evolution from multivariate sequential patterns.

Methods

In this paper, we propose a method to extract a new type of patterns in the clinical domain called Jumping Diagnostic Odds Ratio Sequential Patterns (JDORSP). The aim of this method is to employ the odds ratio to identify a concise set of sequential patterns that represent a patient’s state with a statistically significant protection factor (i.e., a pattern associated with patients that survive) and those extensions whose evolution suddenly changes the patient’s clinical state, thus making the sequential patterns a statistically significant risk factor (i.e., a pattern associated with patients that do not survive), or vice versa.

Results

The results of our experiments highlight that our method reduces the number of sequential patterns obtained with state-of-the-art pattern reduction methods by over 95%. Only by achieving this drastic reduction can medical experts carry out a comprehensive clinical evaluation of the patterns that might be considered medical knowledge regarding the temporal evolution of the patients. We have evaluated the surprisingness and relevance of the sequential patterns with clinicians, and the most interesting fact is the high surprisingness of the extensions of the patterns that become a protection factor, that is, the patients that recover after several days of being at high risk of dying.

Conclusions

Our proposed method with which to extract JDORSP generates a set of interpretable multivariate sequential patterns with new knowledge regarding the temporal evolution of the patients. The number of patterns is greatly reduced when compared to those generated by other methods and measures of interest. An additional advantage of this method is that it does not require any parameters or thresholds, and that the reduced number of patterns allows a manual evaluation.
Endothelial dysfunction and persistent inflammation in severe post-COVID-19 patients: implications for gas exchange
Authors: Alfaro Enrique , Díaz-García Elena , García-Tovar Sara , Galera Raúl , Casitas Raquel , Torres-Vargas María , López-Fernández Cristina , Añón José M. , García-Río Francisco , Cubillos-Zapata Carolina
Published: June 2024

Background

Understanding the enduring respiratory consequences of severe COVID-19 is crucial for comprehensive patient care. This study aims to evaluate the impact of post-COVID conditions on respiratory sequelae of severe acute respiratory distress syndrome (ARDS).

Methods

We examined 88 survivors of COVID-19-associated severe ARDS six months post-intensive care unit (ICU) discharge. Assessments included clinical and functional evaluation as well as plasma biomarkers of endothelial dysfunction, inflammation, and viral response. Additionally, an in vitro model using human umbilical vein endothelial cells (HUVECs) explored the direct impact of post-COVID plasma on endothelial function.

Results

Post-COVID patients with impaired gas exchange demonstrated persistent endothelial inflammation marked by elevated ICAM-1, IL-8, CCL-2, and ET-1 plasma levels. Concurrently, systemic inflammation, evidenced by NLRP3 overexpression and elevated levels of IL-6, sCD40-L, and C-reactive protein, was associated with endothelial dysfunction biomarkers and increased in post-COVID patients with impaired gas exchange. T-cell activation, reflected in CD69 expression, and persistently elevated levels of interferon-β (IFN-β) further contributed to sustained inflammation. The in vitro model confirmed that patient plasma, with altered levels of sCD40-L and IFN-β proteins, has the capacity to alter endothelial function.

Conclusions

Six months post-ICU discharge, survivors of COVID-19-associated ARDS exhibited sustained elevation in endothelial dysfunction biomarkers, correlating with the severity of impaired gas exchange. NLRP3 inflammasome activity and persistent T-cell activation indicate on going inflammation contributing to persistent endothelial dysfunction, potentially intensified by sustained viral immune response.
Assessment of bacteriocin production by clinical Pseudomonas aeruginosa isolates and their potential as therapeutic agents
Authors: Charkhian Hamed , Soleimannezhadbari Ehsan , Bodaqlouei Amin , Lotfollahi Lida , Lotfi Hajie , Yousefi Nesa , Shojadel Ehsan , Gholinejad Zafar
Published: June 2024

Introduction

Bacterial infections and the rising antimicrobial resistance pose a significant threat to public health. Pseudomonas aeruginosa produces bacteriocins like pyocins, especially S-type pyocins, which are promising for biological applications. This research focuses on clinical P. aeruginosa isolates to assess their bacteriocin production, inhibitory spectrum, chemical structure, antibacterial agents, and preservative potential.

Methods

The identification of P. aeruginosa was conducted through both phenotypic and molecular approaches. The inhibitory spectrum and antibacterial potential of the isolates were assessed. The kinetics of antibacterial peptide production were investigated, and the activity of bacteriocin was quantified in arbitrary units (AU ml−1). Physico-chemical characterization of the antibacterial peptides was performed. Molecular weight estimation was carried out using SDS–PAGE. qRT-PCR analysis was employed to validate the expression of the selected candidate gene.

Result

The antibacterial activity of P. aeruginosa was attributed to the secretion of bacteriocin compounds, which belong to the S-type pyocin family. The use of mitomycin C led to a significant 65.74% increase in pyocin production by these isolates. These S-type pyocins exhibited the ability to inhibit the growth of both Gram-negative (P. mirabilis and P. vulgaris) and Gram-positive (S. aureus, S. epidermidis, E. hirae, S. pyogenes, and S. mutans) bacteria. The molecular weight of S-type pyocin was 66 kDa, and its gene expression was confirmed through qRT-PCR.

Conclusion

These findings suggest that S-type pyocin hold significant potential as therapeutic agents against pathogenic strains. The Physico-chemical resistance of S-type pyocin underscores its potential for broad applications in the pharmaceutical, hygiene, and food industries.
A comprehensive approach to lifestyle intervention based on a calorie-restricted diet ameliorates liver fat in overweight/obese patients with NAFLD: a multicenter randomized controlled trial in China
Authors: Liu Zhong , Jin Piaopiao , Liu Yuping , Zhang Zhimian , Wu Xiangming , Weng Min , Cao Suyan , Wang Yan , Zeng Chang , Yang Rui , Liu Chenbing , Sun Ping , Tian Cuihuan , Li Nan , Zeng Qiang
Published: June 2024

Background

Nonalcoholic fatty liver disease (NAFLD) is a globally increasing health epidemic. Lifestyle intervention is recommended as the main therapy for NAFLD. However, the optimal approach is still unclear. This study aimed to evaluate the effects of a comprehensive approach of intensive lifestyle intervention (ILI) concerning enhanced control of calorie-restricted diet (CRD), exercise, and personalized nutrition counseling on liver steatosis and extrahepatic metabolic status in Chinese overweight and obese patients with NAFLD.

Methods

This study was a multicenter randomized controlled trial (RCT) conducted across seven hospitals in China. It involved 226 participants with a body mass index (BMI) above 25. These participants were randomly assigned to two groups: the ILI group, which followed a low carbohydrate, high protein CRD combined with exercise and intensive counseling from a dietitian, and a control group, which adhered to a balanced CRD along with exercise and standard counseling. The main measure of the study was the change in the fat attenuation parameter (FAP) from the start of the study to week 12, analyzed within the per-protocol set. Secondary measures included changes in BMI, liver stiffness measurement (LSM), and the improvement of various metabolic indexes. Additionally, predetermined subgroup analyses of the FAP were conducted based on variables like gender, age, BMI, ethnicity, hyperlipidemia, and hypertension.

Results

A total of 167 participants completed the whole study. Compared to the control group, ILI participants achieved a significant reduction in FAP (LS mean difference, 16.07 [95% CI: 8.90–23.25] dB/m) and BMI (LS mean difference, 1.46 [95% CI: 1.09–1.82] kg/m2) but not in LSM improvement (LS mean difference, 0.20 [95% CI: -0.19–0.59] kPa). The ILI also substantially improved other secondary outcomes (including ALT, AST, GGT, body fat mass, muscle mass and skeletal muscle mass, triglyceride, fasting blood glucose, fasting insulin, HbA1c, HOMA-IR, HOMA-β, blood pressure, and homocysteine). Further subgroup analyses showed that ILI, rather than control intervention, led to more significant FAP reduction, especially in patients with concurrent hypertension (p < 0.001).

Conclusion

In this RCT, a 12-week intensive lifestyle intervention program led to significant improvements in liver steatosis and other metabolic indicators in overweight and obese Chinese patients suffering from nonalcoholic fatty liver disease. Further research is required to confirm the long-term advantages and practicality of this approach.

Trial registration

This clinical trial was registered on ClinicalTrials.gov (registration number: NCT03972631) in June 2019.
Mitochondrial DNA release via the mitochondrial permeability transition pore activates the cGAS-STING pathway, exacerbating inflammation in acute Kawasaki disease
Authors: Wei Ke , Chen Tao , Fang Hao , Shen Xianjuan , Tang Zhiyuan , Zhao Jianmei
Published: June 2024

Background

Kawasaki disease (KD) is an immune vasculitis of unknown origin, characterized by transient inflammation. The activation of the cGAS-STING pathway, triggered by mitochondrial DNA (mtDNA) release, has been implicated in the onset of KD. However, its specific role in the progression of inflammation during KD's acute phase remains unclear.

Methods

We measured mtDNA and 2’3’-cGAMP expression in KD patient serum using RT-qPCR and ELISA. A murine model of KD was induced by injecting Lactobacillus casei cell wall extract (LCWE), after which cGAS-STING pathway activation and inflammatory markers were assessed via immunohistochemistry, western blot, and RT-qPCR. Human umbilical vein endothelial cells (HUVECs) were treated with KD serum and modulators of the cGAS-STING pathway for comparative analysis. Mitochondrial function was evaluated using Mitosox staining, mPTP opening was quantified by fluorescence microscopy, and mitochondrial membrane potential (MMP) was determined with JC-1 staining.

Results

KD patient serum exhibited increased mtDNA and 2’3’-cGAMP expression, with elevated levels of pathway-related proteins and inflammatory markers observed in both in vivo and in vitro models. TEM confirmed mitochondrial damage, and further studies demonstrated that inhibition of mPTP opening reduced mtDNA release, abrogated cGAS-STING pathway activation, and mitigated inflammation.

Conclusion

These findings indicate that mtDNA released through the mPTP is a critical activator of the cGAS-STING pathway, contributing significantly to KD-associated inflammation. Targeting mtDNA release or the cGAS-STING pathway may offer novel therapeutic approaches for KD management.
Imaging at the nexus: how state of the art imaging techniques can enhance our understanding of cancer and fibrosis
Authors: Baniasadi Alireza , Das Jeeban P. , Prendergast Conor M. , Beizavi Zahra , Ma Hong Y. , Jaber Muhammad Yaman , Capaccione Kathleen M.
Published: June 2024

Both cancer and fibrosis are diseases involving dysregulation of cell signaling pathways resulting in an altered cellular microenvironment which ultimately leads to progression of the condition. The two disease entities share common molecular pathophysiology and recent research has illuminated the how each promotes the other. Multiple imaging techniques have been developed to aid in the early and accurate diagnosis of each disease, and given the commonalities between the pathophysiology of the conditions, advances in imaging one disease have opened new avenues to study the other. Here, we detail the most up-to-date advances in imaging techniques for each disease and how they have crossed over to improve detection and monitoring of the other. We explore techniques in positron emission tomography (PET), magnetic resonance imaging (MRI), second generation harmonic Imaging (SGHI), ultrasound (US), radiomics, and artificial intelligence (AI). A new diagnostic imaging tool in PET/computed tomography (CT) is the use of radiolabeled fibroblast activation protein inhibitor (FAPI). SGHI uses high-frequency sound waves to penetrate deeper into the tissue, providing a more detailed view of the tumor microenvironment. Artificial intelligence with the aid of advanced deep learning (DL) algorithms has been highly effective in training computer systems to diagnose and classify neoplastic lesions in multiple organs. Ultimately, advancing imaging techniques in cancer and fibrosis can lead to significantly more timely and accurate diagnoses of both diseases resulting in better patient outcomes.
Cannabis use motives and associations with personal and work characteristics among Canadian workers: a cross-sectional study
Authors: Carnide Nancy , Chrystoja Bethany R. , Lee Hyunmi , Furlan Andrea D. , Smith Peter M.
Published: June 2024

Background

Research on cannabis use motives has focused on youth. Little is known about motives among working adults, including how work may play a role. This study aimed to describe cannabis use motives and their connection to work, and identify the personal and work correlates of work-related motives among a sample of workers.

Methods

A national, cross-sectional sample of Canadian workers were queried about their cannabis use. Workers reporting past-year cannabis use (n = 589) were asked their motives for using cannabis and whether each motive was related to work or helped them manage at work (i.e., work-related). Multinomial logistic regression analyses were conducted to estimate the associations of personal and work characteristics with work-related cannabis use motives (no work-related motives, < 50% of motives work-related, ≥ 50% of motives work-related).

Results

Use for relaxation (59.3%), enjoyment (47.2%), social reasons (35.3%), coping (35.1%), medical reasons (30.9%), and sleep (29.9%) were the most common motives. Almost 40% of respondents reported one or more of their cannabis use motives were work-related, with coping (19.9%) and relaxation (16.3%) most commonly reported as work-related. Younger age, poorer general health, greater job stress, having a supervisory role, and hazardous work were associated with increased odds of reporting at least some cannabis use motives to be work-related, while work schedule and greater frequency of alcohol use were associated with reduced odds of motives being primarily work-related.

Conclusions

Cannabis use motives among workers are diverse and frequently associated with work. Greater attention to the role of work in motivating cannabis use is warranted.
Agreement and concurrent validity between telehealth and in-person diagnosis of musculoskeletal conditions: a systematic review
Authors: Oh David , To Daphne , Corso Melissa , Murnaghan Kent , Yu Hainan , Cancelliere Carol
Published: June 2024

Objectives

To assess the concurrent validity and inter-rater agreement of the diagnosis of musculoskeletal (MSK) conditions using synchronous telehealth compared to standard in-person clinical diagnosis.

Methods

We searched five electronic databases for cross-sectional studies published in English in peer-reviewed journals from inception to 28 September 2023. We included studies of participants presenting to a healthcare provider with an undiagnosed MSK complaint. Eligible studies were critically appraised using the QUADAS-2 and QAREL criteria. Studies rated as overall low risk of bias were synthesized descriptively following best-evidence synthesis principles.

Results

We retrieved 6835 records and 16 full-text articles. Nine studies and 321 patients were included. Participants had MSK conditions involving the shoulder, elbow, low back, knee, lower limb, ankle, and multiple conditions. Comparing telehealth versus in-person clinical assessments, inter-rater agreement ranged from 40.7% agreement for people with shoulder pain to 100% agreement for people with lower limb MSK disorders. Concurrent validity ranged from 36% agreement for people with elbow pain to 95.1% agreement for people with lower limb MSK conditions.

Discussion

In cases when access to in-person care is constrained, our study implies that telehealth might be a feasible approach for the diagnosis of MSK conditions. These conclusions are based on small cross-sectional studies carried out by similar research teams with similar participant demographics. Additional research is required to improve the diagnostic precision of telehealth evaluations across a larger range of patient groups, MSK conditions, and diagnostic accuracy statistics.
CpG island turnover events predict evolutionary changes in enhancer activity
Authors: Kocher Acadia A. , Dutrow Emily V. , Uebbing Severin , Yim Kristina M. , Rosales Larios María F. , Baumgartner Marybeth , Nottoli Timothy , Noonan James P.
Published: June 2024

Background

Genetic changes that modify the function of transcriptional enhancers have been linked to the evolution of biological diversity across species. Multiple studies have focused on the role of nucleotide substitutions, transposition, and insertions and deletions in altering enhancer function. CpG islands (CGIs) have recently been shown to influence enhancer activity, and here we test how their turnover across species contributes to enhancer evolution.

Results

We integrate maps of CGIs and enhancer activity-associated histone modifications obtained from multiple tissues in nine mammalian species and find that CGI content in enhancers is strongly associated with increased histone modification levels. CGIs show widespread turnover across species and species-specific CGIs are strongly enriched for enhancers exhibiting species-specific activity across all tissues and species. Genes associated with enhancers with species-specific CGIs show concordant biases in their expression, supporting that CGI turnover contributes to gene regulatory innovation. Our results also implicate CGI turnover in the evolution of Human Gain Enhancers (HGEs), which show increased activity in human embryonic development and may have contributed to the evolution of uniquely human traits. Using a humanized mouse model, we show that a highly conserved HGE with a large CGI absent from the mouse ortholog shows increased activity at the human CGI in the humanized mouse diencephalon.

Conclusions

Collectively, our results point to CGI turnover as a mechanism driving gene regulatory changes potentially underlying trait evolution in mammals.
Consultations about randomised controlled trials are shorter and less in-depth for socioeconomically disadvantaged patients compared to socioeconomically advantaged patients: qualitative analysis across three trials
Authors: Popa Mariana , Young Bridget , Rousseau Nikki , Cherry Mary G. , Jenkins Isobel , Cloke Jane , Pettitt Andrew , Jenkinson Michael D. , Ahmed Saiqa , Pemberton Allan R. , Sherratt Frances C.
Published: June 2024

Background

Patients from socioeconomically disadvantaged backgrounds are underserved in randomised controlled trials, yet they experience a much greater burden of disease compared with patients from socioeconomically advantaged areas. It is crucial to make trials more inclusive to ensure that treatments and interventions are safe and effective in real-world contexts. Improving how information about trials is verbally communicated is an unexplored strategy to make trials more inclusive. This study examined how trials are communicated verbally, comparing consultations involving patients from the most and least socioeconomically disadvantaged areas.

Methods

Secondary qualitative analysis of 55 trial consultation transcripts from 41 patients, sampled from 3 qualitative studies embedded in their respective UK multi-site, cancer-related randomised controlled trials. Patients living in the most and least socioeconomically disadvantaged areas, defined using English Indices of Multiple Deprivation decile scores, were purposively sampled. Analysis was largely thematic and drew on the constant comparison method.

Results

Recruiters communicated clinical uncertainty in a similar way for patients living in different socioeconomic areas. Consultations with disadvantaged patients were, on average, half the duration of those with advantaged patients, and tended to involve recruiters providing less in-depth explanations of trial concepts, used phrasing that softened trial arm risks, and described trial processes (e.g. randomisation) using informal or metaphorical phrasing. Disadvantaged and advantaged patients differed in the concerns they expressed; disadvantaged patients voiced fewer concerns and asked fewer questions but were also less likely to be invited to do so by recruiters.

Conclusion

Interactions about trials unfolded in different ways between patients living in different socioeconomic areas, likely due to both patient- and recruiter-related factors. We present considerations for recruiters when discussing trials with patients from socioeconomically disadvantaged backgrounds, aimed at enhancing trial communication. Future research should examine disadvantaged patients’ and recruiters’ experiences of verbal trial communication to inform guidance that addresses the needs and preferences of underserved groups.
Developing an optimal stratification model for colorectal cancer screening and reducing racial disparities in multi-center population-based studies
Authors: Tian Jianbo , Zhang Ming , Zhang Fuwei , Gao Kai , Lu Zequn , Cai Yimin , Chen Can , Ning Caibo , Li Yanmin , Qian Sangni , Bai Hao , Liu Yizhuo , Zhang Heng , Chen Shuoni , Li Xiangpan , Wei Yongchang , Li Bin , Zhu Ying , Yang Jinhua , Jin Mingjuan , Miao Xiaoping , Chen Kun
Published: June 2024

Background

Early detection of colorectal neoplasms can reduce the colorectal cancer (CRC) burden by timely intervention for high-risk individuals. However, effective risk prediction models are lacking for personalized CRC early screening in East Asian (EAS) population. We aimed to develop, validate, and optimize a comprehensive risk prediction model across all stages of the dynamic adenoma-carcinoma sequence in EAS population.

Methods

To develop precision risk-stratification and intervention strategies, we developed three trans-ancestry PRSs targeting colorectal neoplasms: (1) using 148 previously identified CRC risk loci (PRS148); (2) SNPs selection from large-scale meta-analysis data by clumping and thresholding (PRS183); (3) PRS-CSx, a Bayesian approach for genome-wide risk prediction (PRSGenomewide). Then, the performance of each PRS was assessed and validated in two independent cross-sectional screening sets, including 4600 patients with advanced colorectal neoplasm, 4495 patients with non-advanced adenoma, and 21,199 normal individuals from the ZJCRC (Zhejiang colorectal cancer set; EAS) and PLCO (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; European, EUR) studies. The optimal PRS was further incorporated with lifestyle factors to stratify individual risk and ultimately tested in the PLCO and UK Biobank prospective cohorts, totaling 350,013 participants.

Results

Three trans-ancestry PRSs achieved moderately improved predictive performance in EAS compared to EUR populations. Remarkably, the PRSs effectively facilitated a thorough risk assessment across all stages of the dynamic adenoma-carcinoma sequence. Among these models, PRS183 demonstrated the optimal discriminatory ability in both EAS and EUR validation datasets, particularly for individuals at risk of colorectal neoplasms. Using two large-scale and independent prospective cohorts, we further confirmed a significant dose–response effect of PRS183 on incident colorectal neoplasms. Incorporating PRS183 with lifestyle factors into a comprehensive strategy improves risk stratification and discriminatory accuracy compared to using PRS or lifestyle factors separately. This comprehensive risk-stratified model shows potential in addressing missed diagnoses in screening tests (best NPV = 0.93), while moderately reducing unnecessary screening (best PPV = 0.32).

Conclusions

Our comprehensive risk-stratified model in population-based CRC screening trials represents a promising advancement in personalized risk assessment, facilitating tailored CRC screening in the EAS population. This approach enhances the transferability of PRSs across ancestries and thereby helps address health disparity.

Graphical Abstract
Automatic grading of knee osteoarthritis with a plain radiograph radiomics model: combining anteroposterior and lateral images
Authors: Li Wei , Liu Jin , Xiao Zhongli , Zhu Dantian , Liao Jianwei , Yu Wenjun , Feng Jiaxin , Qian Baoxin , Fang Yijie , Li Shaolin
Published: June 2024

Objectives

To establish a radiomics-based automatic grading model for knee osteoarthritis (OA) and evaluate the influence of different body positions on the model’s effectiveness.

Materials and methods

Plain radiographs of a total of 473 pairs of knee joints from 473 patients (May 2020 to July 2021) were retrospectively analyzed. Each knee joint included anteroposterior (AP) and lateral (LAT) images which were randomly assigned to the training cohort and the testing cohort at a ratio of 7:3. First, an assessment of knee OA severity was done by two independent radiologists with Kallgren–Lawrence grading scale. Then, another two radiologists independently delineated the region of interest for radiomic feature extraction and selection. The radiomic classification features were dimensionally reduced and a machine model was conducted using logistic regression (LR). Finally, the classification efficiency of the model was evaluated using receiver operating characteristic curves and the area under the curve (AUC).

Results

The AUC (macro/micro) of the model using a combination of AP and LAT (AP&LAT) images were 0.772/0.778, 0.818/0.799, and 0.864/0.879, respectively. The radiomic features from the combined images achieved better classification performance than the individual position image (p < 0.05). The overall accuracy of the radiomic model with AP&LAT images was 0.727 compared to 0.712 and 0.417 for radiologists with 4 years and 2 years of musculoskeletal diagnostic experience.

Conclusions

A radiomic model constructed by combining the AP&LAT images of the knee joint can better grade knee OA and assist clinicians in accurate diagnosis and treatment.

Critical relevance statement

A radiomic model based on plain radiographs accurately grades knee OA severity. By utilizing the LR classifier and combining AP&LAT images, it improves accuracy and consistency in grading, aiding clinical decision-making, and treatment planning.

Key Points

Radiomic model performed more accurately in K/L grading of knee OA than junior radiologists.

Radiomic features from the combined images achieved better classification performance than the individual position image.

A radiomic model can improve the grading of knee OA and assist in diagnosis and treatment.

Graphical Abstract