bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of environmental exposures on exhaled breath and lung function: NELA Birth Cohort
Authors: Sola-Martínez Rosa A. , Jiménez-Guerrero Pedro , Sánchez-Solís Manuel , Lozano-Terol Gema , Gallego-Jara Julia , Martínez-Vivancos Adrián , Morales Eva , García-Marcos Luis , de Diego Puente Teresa ,   on behalf of the NELA Study Group
Published: August 2024

Introduction

Exposure to environmental factors (i.e.air pollution and second-hand tobacco smoke) have been associated with impaired lung function. However, the impact of environmental factors on lung health is usually evaluated separately and not with an exposomic framework. In this regard, breath analysis could be a noninvasive tool for biomonitoring of global human environmental exposure.

Methods

Data come from 337 mother–child pairs from the Nutrition in Early Childhood Asthma (NELA) birth cohort. Levels of BTEX (benzene, toluene, ethylbenzene and xylenes) in exhaled breath from mothers and children at 3 months after birth were estimated using gas chromatography–mass spectrometry. Short-term residential exposures (breath sampling day and 15 days before breath sampling) to nitrogen dioxide, particulate matter (PM2.5) and ozone were determined by chemical dispersion/transport modelling. Forced vital capacity, forced expiratory volume in 0.5 s (FEV0.5) and forced expiratory flow at 75% of FVC and at 25%–75% of FVC were measured in infants according to the raised-volume rapid thoracoabdominal compression technique.

Results

The results showed significant associations between short-term exposure to external agents and levels of benzene and toluene in exhaled breath. It was observed that exhaled levels of benzene and toluene were influenced by smoking status and outdoor air pollution in mothers, and by air pollution in infants (3 months of age). No significant relationship was observed between exposure to maternal tobacco smoking and/or short-term air pollution and lung function in healthy infants. However, there was a significant relationship between FEV0.5and exhaled toluene in children.

Discussion

These findings indicated a significant relationship between environmental exposures and exhaled levels of benzene and toluene, suggesting that breath analysis could be a helpful exposure biomonitoring tool.
Association between impaired diffusion capacity and small airway dysfunction: a cross-sectional study
Authors: Zhou Kunning , Wu Fan , Lu Lifei , Tang Gaoying , Deng Zhishan , Dai Cuiqiong , Zhao Ningning , Wan Qi , Peng Jieqi , Wu Xiaohui , Zeng Xianliang , Cui Jiangyu , Yang Changli , Chen Shengtang , Huang Yongqing , Yu Shuqing , Zhou Yumin , Ran Pixin
Published: August 2024

Background

Small airway dysfunction (SAD) and impaired diffusion capacity of the lungs for carbon monoxide (DLCO) are positively associated with a worse prognosis. Individuals with both dysfunctions have been identified in clinical practice and it is unknown whether they have worse health status or need management. We conducted this study to explore the association between SAD and impairedDLCO, and the difference between the groups with two dysfunctions, with either one dysfunction and with no dysfunction.

Methods

This study involved subjects partly from those who had returned for the third-year follow-up (up to December 2022) of the Early Chronic Obstructive Pulmonary Disease study and those who newly participated. We assessed diffusion capacity, questionnaire, exacerbations, spirometry, impulse oscillometry (IOS) and computed tomography (CT). ImpairedDLCOwas defined asDLCO<80% predicted. Spirometry-defined SAD was defined using the percent predicted values of maximal mid-expiratory flow, and forced expiratory flow at 50% and 75% of forced vital capacity, at least two of these three values being <65% predicted after the use of a bronchodilator. IOS-defined SAD was defined when the difference in resistance at 5 and 20 Hz was >0.07 kPa·L−1·s. CT-defined SAD was defined when the percentage of expiratory low-attenuation areas <−856 HU comprised ≥15% of the total lung volume. Covariate analyses and logistic regression were performed to assess the association between impairedDLCOand SAD.

Results

This study involved 581 subjects. The occurrence of both spirometry- and CT-defined SAD was significantly higher in subjects with impairedDLCOthan normalDLCO. Subjects with two dysfunctions were associated with worse preceding year's exacerbations than controls.

Conclusions

Impaired diffusion capacity is positively associated with SAD. Subjects with impaired diffusion capacity and SAD may have a worse health status and need additional management.
Strain-dependent induction of primary bile acid 7-dehydroxylation by cholic acid
Authors: Vico-Oton Eduard , Volet Colin , Jacquemin Nicolas , Dong Yuan , Hapfelmeier Siegfried , Meibom Karin Lederballe , Bernier-Latmani Rizlan
Published: August 2024

Background

Bile acids (BAs) are steroid-derived molecules with important roles in digestion, the maintenance of host metabolism, and immunomodulation. Primary BAs are synthesized by the host, while secondary BAs are produced by the gut microbiome through transformation of the former. The regulation of microbial production of secondary BAs is not well understood, particularly the production of 7-dehydroxylated BAs, which are the most potent agonists for host BA receptors. The 7-dehydroxylation of cholic acid (CA) is well established and is linked to the expression of a bile acid-inducible (bai) operon responsible for this process. However, little to no 7-dehydroxylation has been reported for other host-derived BAs (e.g., chenodeoxycholic acid, CDCA or ursodeoxycholic acid, UDCA).

Results

Here, we demonstrate that the 7-dehydroxylation of CDCA and UDCA by the human isolate Clostridium scindens is induced when CA is present, suggesting that CA-dependent transcriptional regulation is required for substantial 7-dehydroxylation of these primary BAs. This is supported by the finding that UDCA alone does not promote expression of bai genes. CDCA upregulates expression of the bai genes but the expression is greater when CA is present. In contrast, the murine isolate Extibacter muris exhibits a distinct response; CA did not induce significant 7-dehydroxylation of primary BAs, whereas BA 7-dehydroxylation was promoted upon addition of germ-free mouse cecal content in vitro. However, E. muris was found to 7-dehydroxylate in vivo.

Conclusions

The distinct expression responses amongst strains indicate that bai genes are regulated differently. CA promoted bai operon gene expression and the 7-dehydroxylating activity in C. scindens strains. Conversely, the in vitro activity of E. muris was promoted only after the addition of cecal content and the isolate did not alter bai gene expression in response to CA. The accessory gene baiJ was only upregulated in the C. scindens ATCC 35704 strain, implying mechanistic differences amongst isolates. Interestingly, the human-derived C. scindens strains were also capable of 7-dehydroxylating murine bile acids (muricholic acids) to a limited extent. This study shows novel 7-dehydroxylation activity in vitro resulting from the presence of CA and suggests distinct bai gene expression across bacterial species.
Predicting lymph node metastasis using preoperative parameters in patients with T1 ampulla of vater cancer
Authors: Yoon So Jeong , Hong Seung Soo , Jang Kee-Taek , Yoon So Kyung , Kim Hongbeom , Shin Sang Hyun , Heo Jin Seok , Kang Chang Moo , Kim Kyung Sik , Hwang Ho Kyoung , Han In Woong
Published: August 2024

Background

Lymph node (LN) metastasis is an established prognostic factor for patients with surgically resected ampulla of Vater (AoV) cancer. The standard procedure for radical resection, including removal of regional LNs, is pancreaticoduodenectomy (PD); however, local excision has been considered as an alternative option for patients in the early stage cancer with significant comorbidities. In the present study, we elucidated the preoperative factors associated with LN metastasis to determine the appropriate surgical extent for T1 AoV cancer.

Methods

We included patients who underwent surgery for T1 AoV cancer at Samsung Medical Center and Severance Hospital between 2000 and 2019. Risk factors were analyzed to identify the preoperative parameters associated with LN metastasis or regional LN recurrence during follow-up. Finally, using the identified risk factors, a prediction model was constructed.

Results

Among 342 patients, 311 patients underwent PD, whereas 31 patients underwent transduodenal ampullectomy. Fourty-eight patients had LN metastasis according to pathology report, and two patients presented with regional LN recurrence. Age, carbohydrate antigen 19 − 9 (CA 19 − 9), and tumor differentiation were identified as factors associated with the increased risk of LN metastasis or regional LN recurrence. The area under the curve of the prediction model with these three factors was 0.728.

Conclusion

Our newly developed prediction model using age, CA 19 − 9, and tumor differentiation can help select patients who require PD over local excision. Nevertheless, additional in-depth analysis is warranted to select appropriate surgical extent for patients with presumed T1 AoV cancer.
Estimating the short-term effect of PM2.5 on the mortality of cardiovascular diseases based on instrumental variables
Authors: Zhu Guiming , Zhao Le , Lin Tao , Yu Xuefeng , Sun Hongwei , Zhang Zhiguang , Wang Tong
Published: August 2024

Background

PM2.5 can induce and aggravate the occurrence and development of cardiovascular diseases (CVDs). The objective of our study is to estimate the causal effect of PM2.5 on mortality rates associated with CVDs using the instrumental variables (IVs) method.

Methods

We extracted daily meteorological, PM2.5 and CVDs death data from 2016 to 2020 in Binzhou. Subsequently, we employed the general additive model (GAM), two-stage predictor substitution (2SPS), and control function (CFN) to analyze the association between PM2.5 and daily CVDs mortality.

Results

The 2SPS estimated the association between PM2.5 and daily CVDs mortality as 1.14% (95% CI: 1.04%, 1.14%) for every 10 µg/m3 increase in PM2.5. Meanwhile, the CFN estimated this association to be 1.05% (95% CI: 1.02%, 1.10%). The GAM estimated it as 0.85% (95% CI: 0.77%, 1.05%). PM2.5 also exhibited a statistically significant effect on the mortality rate of patients with ischaemic heart disease, myocardial infarction, or cerebrovascular accidents (P < 0.05). However, no significant association was observed between PM2.5 and hypertension.

Conclusion

PM2.5 was significantly associated with daily CVDs deaths (excluding hypertension). The estimates from the IVs method were slightly higher than those from the GAM. Previous studies based on GAM may have underestimated the impact of PM2.5 on CVDs.
Associations between person-environment fit and mental health - results from the population-based LIFE-Adult-Study
Authors: Jung Franziska U. , Löbner Margrit , Rodriguez Francisca-Saveria , Engel Christoph , Kirsten Toralf , Reyes Nigar , Glaesmer Heide , Hinz Andreas , Witte A. Veronica , Zacher Hannes , Loeffler Markus , Villringer Arno , Luppa Melanie , Riedel-Heller Steffi G.
Published: August 2024

Within occupational settings, mental health of employees can be affected by complex interactions between individuals and their work environment. The aim of this cross-sectional analysis was to investigate the association between person-environment fit and mental health in employees. Data of n = 568 participants from the LIFE adult cohort study was analysed, including socio-demographic characteristics, three dimensions of person-environment fit (P-E fit), symptoms of depression and anxiety. Assessment took place between 2017 and 2021. Statistical analysis included descriptive analyses as well as generalized linear regression models adjusted for age, gender, socioeconomic status, marital status, and job status. Correlational analysis revealed significant associations between age, marital status, SES, employment status, symptoms of depression and anxiety and P-E fit. According to regression models, greater perceived fit between person and organization was associated with lower depression scores and lower symptoms of anxiety. Higher perceived fit between demands and abilities was significantly related to lower severity of depression and anxiety. Similarly, participants reporting a higher fit between needs and supplies, exhibited less symptom severity regarding depression and anxiety. These results underline the importance of person-environment fit regarding mental health. Finding ways to obtain an optimal balance should not only be recognized as an important factor for health and well-being, but might also be beneficial for organizations and employers in the long-term.
Exploring the association between adherence to home-based exercise recommendations and recovery of nonspecific low back pain: a prospective cohort study
Authors: Arensman R. M. , Pisters M. F. , Kloek C. J.J. , Koppenaal T. , Veenhof C. , Ostelo R. J.W.G.
Published: August 2024

Background

Adherence to home-based exercise (HBE) recommendations is critical in physiotherapy for patients with low back pain (LBP). However, limited research has explored its connection with clinical outcomes. This study examined how adherence to HBE relates to changes in physical function, pain intensity, and recovery from LBP in patients undergoing physiotherapy treatment.

Methods

Data from a multicenter cluster randomized controlled trial in the Netherlands involving patients with LBP from 58 primary care physiotherapy practices were used. Adherence to HBE was assessed with the Exercise Adherence Scale (EXAS) at each treatment session. Previously identified adherence trajectories served as a longitudinal measure of adherence and included the classes “declining adherence” (12% of participants), “stable adherence” (45%), and “increasing adherence” (43%). The main outcomes included disability (Oswestry Disability Index), pain (Numeric Pain Rating Scale), and recovery (pain-free for > 4 weeks), which were measured at baseline and after three months. Linear and binomial logistic regression analyses adjusted for confounders were used to examine adherence–outcome relationships.

Results

In the parent trial, 208 participants were included. EXAS scores were available for 173 participants, collected over a median of 4.0 treatment sessions (IQR 3.0 to 6.0). Forty-five (28.5%) patients considered themselves to have recovered after three months. The median changes in the Oswestry Disability Index and Numeric Pain Rating Scale were − 8 (IQR − 1 to -20) and − 2 (IQR − 0.5 to -4), respectively. The mean EXAS scores varied among patient classes: “declining adherence” (46.0, SD 19.4), “stable adherence” (81.0, SD 12.4), and “increasing adherence” (39.9, SD 25.3), with an overall mean of 59.2 (SD 25.3). No associations between adherence and changes in physical functioning or pain were found in the regression analyses.

Conclusions

No association between adherence to HBE recommendations and changes in clinical outcomes in patients with LBP was found. These findings suggest that the relationship between adherence to HBE recommendations and treatment outcomes may be more complex than initially assumed. Further research using detailed longitudinal data combined with qualitative methods to investigate patient motivation and beliefs may lead to a deeper understanding of the relationship between adherence and clinical outcomes in patients with LBP.
Ferula latisecta gels for synthesis of zinc/silver binary nanoparticles: antibacterial effects against gram-negative and gram-positive bacteria and physicochemical characteristics
Authors: Es-haghi Ali , Amiri Mohammad Sadegh , Taghavizadeh Yazdi Mohammad Ehsan
Published: August 2024

This study explores the potential antibacterial applications of zinc oxide nanoparticles (ZnO NPs) enhanced with silver (Ag) using plant gel (ZnO-AgO NPs). The problem addressed is the increasing prevalence of pathogenic bacteria and the need for new, effective antimicrobial agents. ZnO NPs possess distinctive physicochemical properties that enable them to selectively target bacterial cells. Their small size and high surface area-to-volume ratio allow efficient cellular uptake and interaction with bacterial cells. In this study, the average size of the synthesized ZnO-Ag nanoparticles was 77.1 nm, with a significant standard deviation of 33.7 nm, indicating a wide size distribution. The nanoparticles demonstrated remarkable antibacterial efficacy against gram-negative and gram-positive bacteria, with inhibition zones of 14.33 mm for E. coli and 15.66 mm for B. subtilis at a concentration of 300 µg/ml. Minimum inhibitory concentrations (MIC) were determined to be 100 µg/ml for E. coli and 75 µg/ml for S. saprophyticus. Additionally, ZnO-Ag NPs exhibited excellent biocompatibility, making them appropriate for various pharmacological uses. This study utilizes Ferula latisecta gels, offering a sustainable and eco-friendly approach to nanoparticle synthesis. Incorporating of Ag into ZnO NPs significantly enhances their antimicrobial properties, with the combined results showing great inhibition effects on pathogenic microbes. The findings suggest that ZnO-Ag NPs could be a promising candidate for addressing the challenges posed by drug-resistant bacterial infections and enhancing antimicrobial treatments.
Single-arm, first-in-human feasibility study results for an ultra-low-cost insulin pump
Authors: Payne Matthew , Pooke Francis , Wilkinson Tom M. , Holder-Pearson Lui , Chamberlain Bronté , de Bock Martin , Chase J. Geoffrey
Published: August 2024

Background

Use of Continuous Subcutaneous Insulin Infusion (CSII) has been shown to improve glycemic outcomes in Type 1 Diabetes (T1D), but high costs limit accessibility. To address this issue, an inter-operable, open-source Ultra-Low-Cost Insulin Pump (ULCIP) was developed and previously shown to demonstrate comparable delivery accuracy to commercial models in standardised laboratory tests. This study aims to evaluate the updated ULCIP in-vivo, assessing its viability as an affordable alternative for those who cannot afford commercially available devices.

Methods

This first-in-human feasibility study recruited six participants with T1D. During a nine-hour inpatient stay, participants used the ULCIP under clinical supervision. Venous glucose, insulin, and β-Hydroxybutyrate were monitored to assess device performance.

Results

Participants displayed expected blood glucose and blood insulin levels in response to programmed basal and bolus insulin dosing. One participant developed mild ketosis, which was treated and did not recur when a new pump reservoir was placed. All other participants maintained β-Hydroxybutyrate < 0.6 mmol/L throughout.

Conclusion

The ULCIP safely delivered insulin therapy to users in a supervised inpatient environment. Future work should focus on correcting a pump hardware issue identified in this trial and extending device capabilities for use in closed loop control. Longer-term outpatient studies are warranted.

Trial Registration

The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12623001288617) on the 11 December 2023.
A multicenter cross-sectional study in China revealing the intrinsic relationship between medical students’ grade and their perceptions of the learning environment
Authors: Huang Runzhi , Qian Weijin , Xie Sujie , Cheng Mei , Gong Meiqiong , Xian Shuyuan , Jin Minghao , Zhang Mengyi , Tang Jieling , Lu Bingnan , Yang Yiting , Liu Zhenglin , Qu Mingyu , Ma Haonan , Wu Xinru , Yin Huabin , Wang Xiaonan , Liu Xin , Wang Yue , Chen Wenfang , Lin Min , Zhang Chongyou , Du Erbin , Lin Qing , Huang Zongqiang , Zhang Jie , Zhang Guoyang , Liu Yifan , Chen Yu , Liu Jun , Ji Shizhao
Published: August 2024

Background

Medical school learning environment (MSLE) has a holistic impact on students’ psychosomatic health, academic achievements, and personal development. Students in different grades perceive MSLE in different ways. Thus, it is essential to investigate the specific role of student’s grade in the perception of MSLE.

Methods

Using the Johns Hopkins Learning Environment Scale (JHLES) as a quantification instrument for the perception level of MSLE, 10,901 medical students in 12 universities in China were categorized into low or high JHLES group according to their questionnaires. We investigated the relationship between student’s grade and JHLES category by univariate analysis employing Pearson Chi-square test and Welch’s ANOVA. Then multivariable logistic regression analysis confirmed the predictive efficacy of student’s grade. A nomogram concerning the prediction of low JHLES score probability in medical students was also constructed.

Results

A significant difference between two JHLES categories among students in different grades was observed (p < 0.001), with the proportion of the high JHLES group dominating in grade 1, 5, and the graduate subgroups (p < 0.001). The mean JHLES score declined especially in the third and fourth graders compared to freshmen (p < 0.001), while the mean score among the fifth graders had a remarkable rebound from the third graders (p < 0.001). Most imperatively, identified by multivariable logistic regression analysis, students in grade 3 (OR = 1.470, 95% CI = 1.265–1.709, p < 0.001) and 4 (OR = 1.578, 95% CI = 1.326–1.878, p < 0.001) perceived more negatively than freshmen. The constructed nomogram provided a promising prediction model for student’s low JHLES score probability, with accuracy, accordance, and discrimination (area under the curve (AUC) = 0.627).

Conclusion

The student’s grade was a significant influencing factor in medical students’ perception of MSLE. The perceptions among the third and fourth graders got worse, probably due to the worrying changes in various aspects of MSLE during that period. The relevant and appropriate interventions to improve medical students’ perceptions are urgently needed.
Factors influencing patient experience in hospital wards: a systematic review
Authors: Guan Tingyu , Chen Xiao , Li Junfei , Zhang Yuxia
Published: August 2024

Background

Patient experience plays an essential role in improving clinical effectiveness and patient safety. It’s important to identify factors influencing patient experience and to improve quality of healthcare.

Objective

To identify factors that influence patient experience in hospital wards.

Methods

We conducted a systematic review including six databases; they were PubMed, CINAHL, Embase, PsycInfo, ProQuest, and Cochrane. Studies were included if they met the inclusion criteria. The JBI checklist was used to perform quality appraisal. We used 5 domains of the ecological model to organize and synthesize our findings to comprehensively understand the multi-level factors influencing the issue.

Result

A total of 138 studies were included, and 164 factors were identified. These factors were integrated into 6 domains. All domains but one (survey-related factors) could be mapped onto the attributes of the ecological framework: intrapersonal, interpersonal, institutional, community, and public policy level factors. All factors had mixed effect on patient experience. The intrapersonal level refers to individual characteristics of patients. The interpersonal level refers to interactions between patients and healthcare providers, such as the caring time spent by a nurse. The institutional level refers to organizational characteristics, rules and regulations for operations, such as hospital size and accreditation. The community level refers to relationships among organizations, institutions, and informational networks within defined boundaries, such as a hospital located in a larger population area. Public policy level refers to local, state, national, and global laws and policies, including health insurance policies. The sixth domain, survey-related factors, was added to the framework and included factors such as survey response rate and survey response time.

Conclusion

The factors influencing patient experience are comprehensive, ranging from intrapersonal to public policy. Providers should adopt a holistic and integrated perspective to assess patient experience and develop context-specific interventions to improve the quality of care.

PROSPERO registration number CRD42023401066
Super-enhancer omics in stem cell
Authors: Ma Hongying , Qu Jian , Pang Zicheng , Luo Jian , Yan Min , Xu Weixin , Zhuang Haihui , Liu Linxin , Qu Qiang
Published: August 2024

The hallmarks of stem cells, such as proliferation, self-renewal, development, differentiation, and regeneration, are critical to maintain stem cell identity which is sustained by genetic and epigenetic factors. Super-enhancers (SEs), which consist of clusters of active enhancers, play a central role in maintaining stemness hallmarks by specifically transcriptional model. The SE-navigated transcriptional complex, including SEs, non-coding RNAs, master transcriptional factors, Mediators and other co-activators, forms phase-separated condensates, which offers a toggle for directing diverse stem cell fate. With the burgeoning technologies of multiple-omics applied to examine different aspects of SE, we firstly raise the concept of “super-enhancer omics”, inextricably linking to Pan-omics. In the review, we discuss the spatiotemporal organization and concepts of SEs, and describe links between SE-navigated transcriptional complex and stem cell features, such as stem cell identity, self-renewal, pluripotency, differentiation and development. We also elucidate the mechanism of stemness and oncogenic SEs modulating cancer stem cells via genomic and epigenetic alterations hijack in cancer stem cell. Additionally, we discuss the potential of targeting components of the SE complex using small molecule compounds, genome editing, and antisense oligonucleotides to treat SE-associated organ dysfunction and diseases, including cancer. This review also provides insights into the future of stem cell research through the paradigm of SEs.
Regulation of CD73 on NAD metabolism: Unravelling the interplay between tumour immunity and tumour metabolism
Authors: Zhan Jianhao , Huang Le , Niu Liyan , Lu Wenhui , Sun Chengpeng , Liu Shanshan , Ding Zijun , Li Enliang
Published: August 2024

CD73, a cell surface-bound nucleotidase, serves as a crucial metabolic and immune checkpoint. Several studies have shown that CD73 is widely expressed on immune cells and plays a critical role in immune escape, cell adhesion and migration as a costimulatory molecule for T cells and a factor in adenosine production. However, recent studies have revealed that the protumour effects of CD73 are not limited to merely inhibiting the antitumour immune response. Nicotinamide adenine dinucleotide (NAD+) is a vital bioactive molecule in organisms that plays essential regulatory roles in diverse biological processes within tumours. Accumulating evidence has demonstrated that CD73 is involved in the transport and metabolism of NAD, thereby regulating tumour biological processes to promote growth and proliferation. This review provides a holistic view of CD73-regulated NAD + metabolism as a complex network and further highlights the emerging roles of CD73 as a novel target for cancer therapies.
Assay for interferon gamma release as a novel marker in pediatric patients with systemic lupus erythematosus
Authors: Zhang Song , Li Xue , Chen Huishan , Gao Xianfei , Cai Zhe , Zeng Huasong
Published: August 2024

Background

The interferon-gamma (IFN-γ) release assay (IGRA) is an important laboratory diagnosis for latent Mycobacterium tuberculosis (TB) infection. The TB-IGRA measures the release of IFN-γ from peripheral blood cells, who are exposed to TB antigen (Ag), mitogen (MT), or negative/nil control (NL) in vitro. While, an exceptional higher TB Ag-NL level will reflect an elevation of peripheral lymphocytes released IFN-γ in a same condition. Therefore, we found that the elevated levels of TB Ag-NL could become a new biomarker for the diagnosis and treatment of pediatric systemic lupus erythematosus (SLE) patients.

Methods

We have analyzed the clinical data of 776 children who are underwent TB-IGRA testing in the Department of Allergy and Rheumatology of Guangzhou Women and Children’s Medical Center from 2018 to 2020. To investigate the association between TB Ag-NL and SLE, we have analyzed the clinical data of 47 SLE patients and TB Ag-NL testing results, and then evaluated the association between TB Ag-NL and SLE disease activity.

Results

The TB Ag-NL levels were significantly higher in patients with active SLE than those in inactive SLE (p = 0.0002). The TB Ag-NL levels were positively correlated with the SLE disease activity index (SLEDAI) and laboratory diagnosis parameters. The mean value of TB Ag-NL in SLE patients (0.04191 ± 0.07955, IU/mL) were significantly higher than those in patients with juvenile dermatomyositis (JDM) (0.0158 ± 0.0337, IU/mL, p = 0.036), juvenile idiopathic arthritis (JIA) (0.0162 ± 0.0388, IU/mL, p = 0.001), and healthy controls (HC) (0.0001 ± 0.0027, IU/mL, p = 0.0003). Therefore, the elevated TB Ag-NL levels could serve as a potential diagnostic biomarker of SLE, especially for the active SLE.

Conclusion

The detection of IFN-γ release levels by the TB-IGRA may be useful to assess SLE disease activity in pediatric patients with active SLE.
Activating transcription factor 3 mediates apoptosis and cell cycle arrest in TP53-mutated anaplastic thyroid cancer cells
Authors: Kooti Abolfazl , Abuei Haniyeh , Jaafari Alireza , Taki Shayan , Saberzadeh Jamileh , Farhadi Ali
Published: August 2024

Background

It is believed that loss of p53 function plays a crucial role in the progression of well to poorly differentiated thyroid cancers including anaplastic thyroid carcinoma (ATC). Given the poor prognosis of ATC due to its strong therapeutic resistance, there is a need to establish new therapeutic targets to extend the survival of ATC patients. Activating transcription factor 3 (ATF3) can inhibit the oncogenic activity of mutant p53 and, as a result, contribute to tumor suppression in several TP53-mutated cancers. Herein, we demonstrate that the ectopic overexpression of ATF3 leads to the suppression of oncogenic mutant p53 activity in chemo-resistant 8305 C thyroid cancer cells harboring R273C p53 gene mutation.

Methods

The biological behavior of 8305 C cells was assessed pre- and post-transfection with pCMV6-ATF3 plasmid using MTT assay, fluorescent microscopy, cell cycle, and annexin V/PI flow cytometric analysis. The effect of ectopic ATF3 overexpression on the cellular level of p53 was examined by western blotting assay. The mRNA expression levels of TP53, TAp63, ΔNp63, and SHARP1 were evaluated in ectopic ATF3-expressing cells compared to controls.

Results

The overexpression of ATF3 in 8305 C thyroid cancer cells significantly decreased cell viability and induced apoptosis and cell cycle arrest in vitro. The immunoblotting of p53 protein revealed that ATF3 overexpression significantly increased the level of mutant p53 in 8305C cells compared to mock-transfected control cells. Additionally, elevated mRNA levels of TAp63 and SHARP1 and a decreased mRNA level of ΔNp63 were observed in PCMV6-AC-ATF3-transfected 8305 C cells with significant differences compared to the mock and untreated cells.

Conclusion

In light of our findings, it is evident that therapeutic strategies aimed at increasing ATF3 expression or enhancing the interaction between ATF3 and mutant p53 can be a promising approach for the treatment of p53-mutated metastatic thyroid cancer.
The creation, implementation, and harmonisation of medical standard operating procedures and checklists of Finnish Helicopter Emergency Medical Service units
Authors: Tukia Simo , Pirnes Jari , Nurmi Jouni , Nordquist Hilla
Published: August 2024

Introduction

The purpose of this study was to investigate the creation, implementation, and harmonisation of medical Standard Operating Procedures (SOP) in Finnish Helicopter Emergency Medical Services (HEMS). The research questions are: (1) What factors influence the creation and implementation of medical SOPs for Finnish HEMS units? and (2) What can be done to harmonise the medical SOPs of Finnish HEMS units?

Methods

The research was conducted as a qualitative interview study with HEMS physicians who worked full-time in Finnish HEMS units or had worked in HEMS for more than five years. Three HEMS physicians from each of the six HEMS units in Finland participated in the study (n = 18). The thematic interviews (average duration 32 min) were transcribed (70,176 words in Finnish) and analysed using inductive content analysis.

Results

The results of the first research question formed three main categories: (1) Background to developing medical SOPs and checklists (CLs), (2) Creation of medical SOPs in Finnish HEMS units, and (3) Implementation of medical SOPs and CLs. The main categories were divided into eight upper categories and twelve subcategories. The results of the second research question formed four main categories: (1) Prerequisites for harmonising procedures, (2) System-level changes needed, (3) Integrating common medical SOPs into HEMS, and (4) Cultural change. The main categories were divided into nine upper categories and nine subcategories.

Conclusions

Medical SOPs and CLs are an integral part of Finnish HEMS. Each unit creates its own SOPs and CLs; their development, implementation, and follow-up are relatively unstructured. Harmonising existing SOPs would be possible, but developing common SOPs would require structural changes in HEMS and a stronger sense of community belonging among HEMS physicians.
Current genomic deep learning models display decreased performance in cell type-specific accessible regions
Authors: Kathail Pooja , Shuai Richard W. , Chung Ryan , Ye Chun Jimmie , Loeb Gabriel B. , Ioannidis Nilah M.
Published: August 2024

Background

A number of deep learning models have been developed to predict epigenetic features such as chromatin accessibility from DNA sequence. Model evaluations commonly report performance genome-wide; however, cis regulatory elements (CREs), which play critical roles in gene regulation, make up only a small fraction of the genome. Furthermore, cell type-specific CREs contain a large proportion of complex disease heritability.

Results

We evaluate genomic deep learning models in chromatin accessibility regions with varying degrees of cell type specificity. We assess two modeling directions in the field: general purpose models trained across thousands of outputs (cell types and epigenetic marks) and models tailored to specific tissues and tasks. We find that the accuracy of genomic deep learning models, including two state-of-the-art general purpose models―Enformer and Sei―varies across the genome and is reduced in cell type-specific accessible regions. Using accessibility models trained on cell types from specific tissues, we find that increasing model capacity to learn cell type-specific regulatory syntax―through single-task learning or high capacity multi-task models―can improve performance in cell type-specific accessible regions. We also observe that improving reference sequence predictions does not consistently improve variant effect predictions, indicating that novel strategies are needed to improve performance on variants.

Conclusions

Our results provide a new perspective on the performance of genomic deep learning models, showing that performance varies across the genome and is particularly reduced in cell type-specific accessible regions. We also identify strategies to maximize performance in cell type-specific accessible regions.
Annelid methylomes reveal ancestral developmental and aging-associated epigenetic erosion across Bilateria
Authors: Guynes Kero , Sarre Luke A. , Carrillo-Baltodano Allan M. , Davies Billie E. , Xu Lan , Liang Yan , Martín-Zamora Francisco M. , Hurd Paul J. , de Mendoza Alex , Martín-Durán José M.
Published: August 2024

Background

DNA methylation in the form of 5-methylcytosine (5mC) is the most abundant base modification in animals. However, 5mC levels vary widely across taxa. While vertebrate genomes are hypermethylated, in most invertebrates, 5mC concentrates on constantly and highly transcribed genes (gene body methylation; GbM) and, in some species, on transposable elements (TEs), a pattern known as “mosaic”. Yet, the role and developmental dynamics of 5mC and how these explain interspecies differences in DNA methylation patterns remain poorly understood, especially in Spiralia, a large clade of invertebrates comprising nearly half of the animal phyla.

Results

Here, we generate base-resolution methylomes for three species with distinct genomic features and phylogenetic positions in Annelida, a major spiralian phylum. All possible 5mC patterns occur in annelids, from typical invertebrate intermediate levels in a mosaic distribution to hypermethylation and methylation loss. GbM is common to annelids with 5mC, and methylation differences across species are explained by taxon-specific transcriptional dynamics or the presence of intronic TEs. Notably, the link between GbM and transcription decays during development, alongside a gradual and global, age-dependent demethylation in adult stages. Additionally, reducing 5mC levels with cytidine analogs during early development impairs normal embryogenesis and reactivates TEs in the annelid Owenia fusiformis.

Conclusions

Our study indicates that global epigenetic erosion during development and aging is an ancestral feature of bilateral animals. However, the tight link between transcription and gene body methylation is likely more important in early embryonic stages, and 5mC-mediated TE silencing probably emerged convergently across animal lineages.
Digital remote assessment of speech acoustics in cognitively unimpaired adults: feasibility, reliability and associations with amyloid pathology
Authors: van den Berg Rosanne L. , de Boer Casper , Zwan Marissa D. , Jutten Roos J. , van Liere Mariska , van de Glind Marie-Christine A.B.J. , Dubbelman Mark A. , Schlüter Lisa Marie , van Harten Argonde C. , Teunissen Charlotte E. , van de Giessen Elsmarieke , Barkhof Frederik , Collij Lyduine E. , Robin Jessica , Simpson William , Harrison John E , van der Flier Wiesje M. , Sikkes Sietske A.M.
Published: August 2024

Background

Digital speech assessment has potential relevance in the earliest, preclinical stages of Alzheimer’s disease (AD). We evaluated the feasibility, test-retest reliability, and association with AD-related amyloid-beta (Aβ) pathology of speech acoustics measured over multiple assessments in a remote setting.

Methods

Fifty cognitively unimpaired adults (Age 68 ± 6.2 years, 58% female, 46% Aβ-positive) completed remote, tablet-based speech assessments (i.e., picture description, journal-prompt storytelling, verbal fluency tasks) for five days. The testing paradigm was repeated after 2–3 weeks. Acoustic speech features were automatically extracted from the voice recordings, and mean scores were calculated over the 5-day period. We assessed feasibility by adherence rates and usability ratings on the System Usability Scale (SUS) questionnaire. Test-retest reliability was examined with intraclass correlation coefficients (ICCs). We investigated the associations between acoustic features and Aβ-pathology, using linear regression models, adjusted for age, sex and education.

Results

The speech assessment was feasible, indicated by 91.6% adherence and usability scores of 86.0 ± 9.9. High reliability (ICC ≥ 0.75) was found across averaged speech samples. Aβ-positive individuals displayed a higher pause-to-word ratio in picture description (B = -0.05, p = 0.040) and journal-prompt storytelling (B = -0.07, p = 0.032) than Aβ-negative individuals, although this effect lost significance after correction for multiple testing.

Conclusion

Our findings support the feasibility and reliability of multi-day remote assessment of speech acoustics in cognitively unimpaired individuals with and without Aβ-pathology, which lays the foundation for the use of speech biomarkers in the context of early AD.
Extraocular muscle Diffusion Weighted Imaging as a quantitative metric of posterior orbital involvement in thyroid associated orbitopathy
Authors: George Nicole M. , Feeney Claire , Lee Vickie , Avari Parizad , Ali Amina , Madani Gitta , Lingam Ravi Kumar , Bhatia Kunwar S.
Published: August 2024

Objectives

The clinical activity score (CAS) and European severity scale (ESS) are established clinical tools to assess thyroid eye disease (TED) but are limited in terms of subjectivity and their reliability in non-Caucasian individuals, and can underestimate significant disease in the posterior orbit. Preliminary data from pilot studies have shown that diffusion-weighted imaging (DWI) using extraocular muscle (EOM) apparent diffusion coefficient (ADC) measurements may provide complementary information in TED. This study expands on previous research to assess for correlations between clinical scores and EOM-ADCs in stratifying disease activity and severity in a large patient cohort from an ethnically diverse population.

Methods

A retrospective review of TED clinics between 2011 and 2021 identified 96 patients with a documented CAS and ESS and an orbital MRI that included DWI. From regions of interest manually placed on EOM bellies, the highest ADC was computed for each patient and analysed for correlations and associations with CAS and ESS using Spearman Rank correlation and Mann–Whitney U tests, and any potential discriminatory cut-offs using Receiver Operator Curve analyses. A p-value < 0.05 indicated statistical significance.

Results

EOM-ADCs showed a positive association with CAS (p ≤ 0.001). EOM-ADCs were higher in sight-threatening compared to mild disease (p ≤ 0.01). A cut-off of 995 mm2/s achieved AUC = 0.7744, equating to 77% sensitivity and 67% specificity for discrimination between mild-moderate and sight-threatening disease.

Conclusion

EOM-ADCs correlate with higher scores of disease severity and activity in TED. Besides providing quantitative data to support clinical tools, EOM-ADC cut-offs may identify patients at risk of developing sight-threatening diseases.

Critical relevance statement

This study critically evaluates the limitations of conventional clinical assessment tools for TED and demonstrates the utility of DWI scans with ADC measurements in identifying active disease, offering valuable insights to advance clinical radiology practice.

Key Points

Conventional tools for TED assessment have subjective limitations.

ADCs from non-echoplanar diffusion-weighted imaging correlate with clinical activity.

Non-echoplanar diffusion-weighted imaging offers quantitative assessment to aid clinical practice reliability.

Graphical Abstract
Preoperative prediction of microvascular invasion risk in hepatocellular carcinoma with MRI: peritumoral versus tumor region
Authors: Wei Guangya , Fang Guoxu , Guo Pengfei , Fang Peng , Wang Tongming , Lin Kecan , Liu Jingfeng
Published: August 2024

Objectives

To explore the predictive performance of tumor and multiple peritumoral regions on dynamic contrast-enhanced magnetic resonance imaging (MRI), to identify optimal regions of interest for developing a preoperative predictive model for the grade of microvascular invasion (MVI).

Methods

A total of 147 patients who were surgically diagnosed with hepatocellular carcinoma, and had a maximum tumor diameter ≤ 5 cm were recruited and subsequently divided into a training set (n = 117) and a testing set (n = 30) based on the date of surgery. We utilized a pre-trained AlexNet to extract deep learning features from seven different regions of the maximum transverse cross-section of tumors in various MRI sequence images. Subsequently, an extreme gradient boosting (XGBoost) classifier was employed to construct the MVI grade prediction model, with evaluation based on the area under the curve (AUC).

Results

The XGBoost classifier trained with data from the 20-mm peritumoral region showed superior AUC compared to the tumor region alone. AUC values consistently increased when utilizing data from 5-mm, 10-mm, and 20-mm peritumoral regions. Combining arterial and delayed-phase data yielded the highest predictive performance, with micro- and macro-average AUCs of 0.78 and 0.74, respectively. Integration of clinical data further improved AUCs values to 0.83 and 0.80.

Conclusion

Compared with those of the tumor region, the deep learning features of the peritumoral region provide more important information for predicting the grade of MVI. Combining the tumor region and the 20-mm peritumoral region resulted in a relatively ideal and accurate region within which the grade of MVI can be predicted.

Clinical relevance statement

The 20-mm peritumoral region holds more significance than the tumor region in predicting MVI grade. Deep learning features can indirectly predict MVI by extracting information from the tumor region and directly capturing MVI information from the peritumoral region.

Key Points

We investigated tumor and different peritumoral regions, as well as their fusion.

MVI predominantly occurs in the peritumoral region, a superior predictor compared to the tumor region.

The peritumoral 20 mm region is reasonable for accurately predicting the three-grade MVI.

Graphical Abstract
The policies on the use of large language models in radiological journals are lacking: a meta-research study
Authors: Zhong Jingyu , Xing Yue , Hu Yangfan , Lu Junjie , Yang Jiarui , Zhang Guangcheng , Mao Shiqi , Chen Haoda , Yin Qian , Cen Qingqing , Jiang Run , Chu Jingshen , Song Yang , Lu Minda , Ding Defang , Ge Xiang , Zhang Huan , Yao Weiwu
Published: August 2024

Objective

To evaluate whether and how the radiological journals present their policies on the use of large language models (LLMs), and identify the journal characteristic variables that are associated with the presence.

Methods

In this meta-research study, we screened Journals from the Radiology, Nuclear Medicine and Medical Imaging Category, 2022 Journal Citation Reports, excluding journals in non-English languages and relevant documents unavailable. We assessed their LLM use policies: (1) whether the policy is present; (2) whether the policy for the authors, the reviewers, and the editors is present; and (3) whether the policy asks the author to report the usage of LLMs, the name of LLMs, the section that used LLMs, the role of LLMs, the verification of LLMs, and the potential influence of LLMs. The association between the presence of policies and journal characteristic variables was evaluated.

Results

The LLM use policies were presented in 43.9% (83/189) of journals, and those for the authors, the reviewers, and the editor were presented in 43.4% (82/189), 29.6% (56/189) and 25.9% (49/189) of journals, respectively. Many journals mentioned the aspects of the usage (43.4%, 82/189), the name (34.9%, 66/189), the verification (33.3%, 63/189), and the role (31.7%, 60/189) of LLMs, while the potential influence of LLMs (4.2%, 8/189), and the section that used LLMs (1.6%, 3/189) were seldomly touched. The publisher is related to the presence of LLM use policies (p < 0.001).

Conclusion

The presence of LLM use policies is suboptimal in radiological journals. A reporting guideline is encouraged to facilitate reporting quality and transparency.

Critical relevance statement

It may facilitate the quality and transparency of the use of LLMs in scientific writing if a shared complete reporting guideline is developed by stakeholders and then endorsed by journals.

Key Points

The policies on LLM use in radiological journals are unexplored.

Some of the radiological journals presented policies on LLM use.

A shared complete reporting guideline for LLM use is desired.

Graphical Abstract