bluuebunny/crossref_metadata_2025 huggingface dataset:
Utilization of EHRs for clinical trials: a systematic review
Authors: Kalankesh Leila R. , Monaghesh Elham
Published: March 2024

Background and objective

Clinical trials are of high importance for medical progress. This study conducted a systematic review to identify the applications of EHRs in supporting and enhancing clinical trials.

Materials and methods

A systematic search of PubMed was conducted on 12/3/2023 to identify relevant studies on the use of EHRs in clinical trials. Studies were included if they (1) were full-text journal articles, (2) were written in English, (3) examined applications of EHR data to support clinical trial processes (e.g. recruitment, screening, data collection). A standardized form was used by two reviewers to extract data on: study design, EHR-enabled process(es), related outcomes, and limitations.

Results

Following full-text review, 19 studies met the predefined eligibility criteria and were included. Overall, included studies consistently demonstrated that EHR data integration improves clinical trial feasibility and efficiency in recruitment, screening, data collection, and trial design.

Conclusions

According to the results of the present study, the use of Electronic Health Records in conducting clinical trials is very helpful. Therefore, it is better for researchers to use EHR in their studies for easy access to more accurate and comprehensive data. EHRs collects all individual data, including demographic, clinical, diagnostic, and therapeutic data. Moreover, all data is available seamlessly in EHR. In future studies, it is better to consider the cost-effectiveness of using EHR in clinical trials.
Development and validation of a multi-modal ultrasomics model to predict response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer
Authors: Qin Qiong , Gan Xiangyu , Lin Peng , Pang Jingshu , Gao Ruizhi , Wen Rong , Liu Dun , Tang Quanquan , Liu Changwen , He Yun , Yang Hong , Wu Yuquan
Published: March 2024

Objectives

To assess the performance of multi-modal ultrasomics model to predict efficacy to neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) and compare with the clinical model.

Materials and methods

This study retrospectively included 106 patients with LARC who underwent total mesorectal excision after nCRT between April 2018 and April 2023 at our hospital, randomly divided into a training set of 74 and a validation set of 32 in a 7: 3 ratios. Ultrasomics features were extracted from the tumors’ region of interest of B-mode ultrasound (BUS) and contrast-enhanced ultrasound (CEUS) images based on PyRadiomics. Mann-Whitney U test, spearman, and least absolute shrinkage and selection operator algorithms were utilized to reduce features dimension. Five models were built with ultrasomics and clinical analysis using multilayer perceptron neural network classifier based on python. Including BUS, CEUS, Combined_1, Combined_2 and Clinical models. The diagnostic performance of models was assessed with the area under the curve (AUC) of the receiver operating characteristic. The DeLong testing algorithm was utilized to compare the models’ overall performance.

Results

The AUC (95% confidence interval [CI]) of the five models in the validation cohort were as follows: BUS 0.675 (95%CI: 0.481–0.868), CEUS 0.821 (95%CI: 0.660–0.983), Combined_1 0.829 (95%CI: 0.673–0.985), Combined_2 0.893 (95%CI: 0.780-1.000), and Clinical 0.690 (95%CI: 0.509–0.872). The Combined_2 model was the best in the overall prediction performance, showed significantly better compared to the Clinical model after DeLong testing (P < 0.01). Both univariate and multivariate logistic regression analyses showed that age (P < 0.01) and clinical stage (P < 0.01) could be an independent predictor of efficacy after nCRT in patients with LARC.

Conclusion

The ultrasomics model had better diagnostic performance to predict efficacy to nCRT in patients with LARC than the Clinical model.
Unified deep learning models for enhanced lung cancer prediction with ResNet-50–101 and EfficientNet-B3 using DICOM images
Authors: Kumar Vinod , Prabha Chander , Sharma Preeti , Mittal Nitin , Askar S. S. , Abouhawwash Mohamed
Published: March 2024

Significant advancements in machine learning algorithms have the potential to aid in the early detection and prevention of cancer, a devastating disease. However, traditional research methods face obstacles, and the amount of cancer-related information is rapidly expanding. The authors have developed a helpful support system using three distinct deep-learning models, ResNet-50, EfficientNet-B3, and ResNet-101, along with transfer learning, to predict lung cancer, thereby contributing to health and reducing the mortality rate associated with this condition. This offer aims to address the issue effectively. Using a dataset of 1,000 DICOM lung cancer images from the LIDC-IDRI repository, each image is classified into four different categories. Although deep learning is still making progress in its ability to analyze and understand cancer data, this research marks a significant step forward in the fight against cancer, promoting better health outcomes and potentially lowering the mortality rate. The Fusion Model, like all other models, achieved 100% precision in classifying Squamous Cells. The Fusion Model and ResNet-50 achieved a precision of 90%, closely followed by EfficientNet-B3 and ResNet-101 with slightly lower precision. To prevent overfitting and improve data collection and planning, the authors implemented a data extension strategy. The relationship between acquiring knowledge and reaching specific scores was also connected to advancing and addressing the issue of imprecise accuracy, ultimately contributing to advancements in health and a reduction in the mortality rate associated with lung cancer.
Preserving visual acuity: a compelling 12-year case study of controlling neovascular age-related macular degeneration
Authors: Tomás Rita O. , Campos António , Oliveira Nuno , Soares Pedro , Sousa João P.
Published: March 2024

Introduction

In neovascular age-related macular degeneration (nAMD) trials, anti-VEGF injection frequency decreases after the first year, while outcomes remain primarily related to the number of injections. To the best of our knowledge, there are no reports of maintaining the best corrected visual acuity (BCVA) for more than 7 years in extension studies.

Objective

To report a 12-year follow-up of a real-world case of nAMD where BCVA was preserved from declining.

Case description

A 67-year-old Caucasian female presented to our department in June 2010 due to decreased vision in her left eye (LE) within the preceding months. Examination showed a BCVA of 85 letters (L) in the right eye (RE) and 35 L in the LE. Fundus examination showed drusen in the macula of both eyes. Macular edema, loss of the macular lutein pigment, macular hypo/hyperpigmentation were observed in the LE. A diagnosis of Type 2 choroidal neovascular membrane (CNV) in the LE was established and within two months a Type 1 CNV developed in the RE. She undergone 9 injections of bevacizumab (six) and ranibizumab (three) within the first year of treatment in the LE and seven injections of ranibizumab within the first year in the RE.

Results

The LE had a mean of 5.2 injections per year, and the RE had a mean of 7.5 injections per year, from 2010 to 2022. RE's BCVA dropped by 8L (85L to 77L) and central retinal thickness (CRT) increased by 16 μm (276 μm to 292 μm) while LE’s BCVA increased by 28L (35L to 63L) and CRT decreased by 369 μm (680 μm to 311 μm), at the twelfth year.

Conclusions

Although the final visual outcome depends on baseline BCVA and lesion type or size, the number of injections is paramount in preserving BCVA and achieving favorable functional outcomes in nAMD, even after 12 years of treatment.
Actions targeting the integration of peer workforces in mental health organisations: a mixed-methods systematic review
Authors: Reeves Verity , McIntyre Heather , Loughhead Mark , Halpin Matthew Anthony , Procter Nicholas
Published: March 2024

Background

Lived experience workforces are one of the fastest growing emerging disciplines in Australian mental health service settings. Individuals with lived and living experience of mental distress employed in mental health services, often referred to as peer or lived experience workers, are widely considered essential for mental health recovery and reform. Despite vast growth of this workforce, concerns remain over the widespread integration of peer workforces to align with recommended movement of healthcare services toward greater recovery-orientated and person-centered practices. Previous research has identified barriers for peer work integration including a lack of clear role definition, inadequate training, and poor supportive organisational culture. Stigma, discrimination and a lack of acceptance by colleagues are also common themes. This systematic review seeks to identify organisational actions to support integration of peer workforces for improved mental health service delivery.

Method

A systematic search was conducted through online databases (n = 8) between January 1980 to November 2023. Additional data were sourced from conference proceedings, hand searching grey literature and scanning reference lists. Qualitative data was extracted and synthesised utilising narrative synthesis to identify key themes and findings reported adhere to PRISMA guidelines. The review protocol was registered with Prospero (CRD: 42,021,257,013).

Results

Four key actions were identified: education and training, organisational readiness, Structural adjustments, resourcing and support and, demonstrated commitment to peer integration and recovery practice.

Conclusions

The study identifies actions for mental health service organisations and system leaders to adopt in support of integrating peer and lived experience workforces in service delivery.
Reliability and validity of the Patient Health Questionnaire-4 scale and its subscales of depression and anxiety among US adults based on nativity
Authors: Adzrago David , Walker Timothy J. , Williams Faustine
Published: March 2024

Background

The burdens of anxiety and depression symptoms have significantly increased in the general US population, especially during this COVID-19 epidemiological crisis. The first step in an effective treatment for anxiety and depression disorders is screening. The Patient Health Questionnaire-4 (PHQ-4, a 4-item measure of anxiety/depression) and its subscales (PHQ-2 [a 2-item measure of depression] and Generalized Anxiety Disorder [GAD-2, a 2-item measure of anxiety]) are brief but effective mass screening instruments for anxiety and depression symptoms in general populations. However, little to no study examined the psychometric properties (i.e., reliability and validity) of the PHQ-4 and its subscales (PHQ-2 and GAD-2) in the general US adult population or based on US nativity (i.e., foreign-born vs. the US-born). We evaluated the psychometric properties of the PHQ-4 and its subscales in US adults, as well as the psychometric equivalence of the PHQ-4 scale based on nativity.

Methods

We conducted a cross-sectional survey of 5,140 adults aged ≥ 18 years. We examined the factorial validity and dimensionality of the PHQ-4 with confirmatory factor analysis (CFA). A multiple-group confirmatory factor analysis (MCFA) was used to evaluate the comparability of the PHQ-4 across nativity groups. Reliability indices were assessed. Also, the scales’ construct validities were assessed by examining the associations of both the PHQ-4 and its subscales’ scores with the sociodemographic characteristics and the 3-item UCLA Loneliness scale.

Results

The internal consistencies were high for the PHQ-4 scale (α = 0.92) and its subscales of PHQ-2 (α = 0.86) and GAD-2 (α = 0.90). The CFA fit indices showed evidence for the two-factor structure of the PHQ-4. The two factors (i.e., anxiety and depression) were significantly correlated (r = 0.92). The MCFA demonstrated measurement invariance of the PHQ-4 across the nativity groups, but the model fits the data better in the foreign-born group. There were significant associations of the PHQ-4 scale and its subscales’ scores with the sociodemographic characteristics and the UCLA Loneliness scale (all p < 0.001).

Conclusions

The PHQ-4 and its subscales are reliable and valid measures to screen anxiety and depression symptoms in the general US adult population, especially in foreign-born individuals during the COVID-19 pandemic.
Incorporating social vulnerability in infectious disease mathematical modelling: a scoping review
Authors: Naidoo Megan , Shephard Whitney , Kambewe Innocensia , Mtshali Nokuthula , Cope Sky , Rubio Felipe Alves , Rasella Davide
Published: March 2024

Background

Highlighted by the rise of COVID-19, climate change, and conflict, socially vulnerable populations are least resilient to disaster. In infectious disease management, mathematical models are a commonly used tool. Researchers should include social vulnerability in models to strengthen their utility in reflecting real-world dynamics. We conducted a scoping review to evaluate how researchers have incorporated social vulnerability into infectious disease mathematical models.

Methods

The methodology followed the Joanna Briggs Institute and updated Arksey and O'Malley frameworks, verified by the PRISMA-ScR checklist. PubMed, Clarivate Web of Science, Scopus, EBSCO Africa Wide Information, and Cochrane Library were systematically searched for peer-reviewed published articles. Screening and extracting data were done by two independent researchers.

Results

Of 4075 results, 89 articles were identified. Two-thirds of articles used a compartmental model (n = 58, 65.2%), with a quarter using agent-based models (n = 24, 27.0%). Overall, routine indicators, namely age and sex, were among the most frequently used measures (n = 42, 12.3%; n = 22, 6.4%, respectively). Only one measure related to culture and social behaviour (0.3%). For compartmental models, researchers commonly constructed distinct models for each level of a social vulnerability measure and included new parameters or influenced standard parameters in model equations (n = 30, 51.7%). For all agent-based models, characteristics were assigned to hosts (n = 24, 100.0%), with most models including age, contact behaviour, and/or sex (n = 18, 75.0%; n = 14, 53.3%; n = 10, 41.7%, respectively).

Conclusions

Given the importance of equitable and effective infectious disease management, there is potential to further the field. Our findings demonstrate that social vulnerability is not considered holistically. There is a focus on incorporating routine demographic indicators but important cultural and social behaviours that impact health outcomes are excluded. It is crucial to develop models that foreground social vulnerability to not only design more equitable interventions, but also to develop more effective infectious disease control and elimination strategies. Furthermore, this study revealed the lack of transparency around data sources, inconsistent reporting, lack of collaboration with local experts, and limited studies focused on modelling cultural indicators. These challenges are priorities for future research.
Impact of smoking reduction on lung cancer risk in patients with COPD who smoked fewer than 30 pack-years: a nationwide population-based cohort study
Authors: Shin Sun Hye , Kim Taeyun , Kim Hyunsoo , Cho Juhee , Kang Danbee , Park Hye Yun
Published: March 2024

Background

The effects of smoking reduction on the incidence of lung cancer in patients with chronic obstructive pulmonary disease (COPD) are not well known. This study aimed to investigate the effects of changes in smoking habits after COPD diagnosis on lung cancer development in patients who smoked less than 30 pack-years.

Methods

This nationwide retrospective cohort study included 16,832 patients with COPD who smoked less than 30 pack-years at the time of COPD diagnosis. Based on changes in smoking habits in the health screening examination data, smokers were categorized into three groups: quitters, reducers, and sustainers. The primary outcome was the risk of lung cancer development, which was estimated using the Cox proportional hazards model. We also modelled the amount of smoking reduction as a continuous variable.

Results

During a median follow-up of 4 years, the cumulative incidence of lung cancer was the highest among sustainers, followed by reducers and quitters. Compared with sustainers, reducers (adjusted HR 0.74, 95% CI:0.56–0.98) and quitters (adjusted HR 0.78, 95% CI:0.64–0.96) had a significantly lower risk of lung cancer. Incidence of lung cancer showed a decreasing trend with a decreasing amount of smoking (P for linearity < 0.01).

Conclusions

In patients with COPD who smoked less than 30 pack-years, smoking reduction and cessation lowered the risk of lung cancer.
Two single lung transplantations from one donor: lung twinning in the LAS era
Authors: Langer Frank , Lepper Philipp M. , Weingard Bettina , Aliyev Parviz , Bals Robert , Wilkens Heinrike
Published: March 2024

Objectives

The implementation of the Lung Allocation Score (LAS) in the Eurotransplant international collaborative framework decreased waiting list mortality, but organ shortage remains a significant problem. Transplantation of two single lungs from one donor into two recipients (lung twinning) may decrease waiting list mortality. We sought to analyze if this strategy can lead to an acceptable intermediate-term outcome.

Methods

Since the LAS-implementation we performed 32 paired single-lung transplantations from 16 postmortal donors. Data and outcome were analyzed retrospectively comparing recipients receiving the first lung (first twins) with recipients receiving the second lung (second twins), left versus right transplantation and restrictive versus obstructive disease.

Results

Survival at one year was 81% and 54% at five years. Veno-venous ECMO had been successfully used as bridge-to-transplant in three patients with ECMO-explantation immediately after surgery. Bronchial anastomotic complications were not observed in any patient. First twins and second twins exhibited similar survival (p = 0.82) despite higher LAS in first twins (median 45 versus 34, p < 0.001) and longer cold ischemic time in second twins (280 ± 83 vs. 478 ± 125 min, p < 0.001). Survival of left and right transplantation was similar (p = 0.45) with similar best post-transplant FEV1 (68 ± 15% versus 62 ± 14%, p = 0.26). Survival was similar in restrictive and obstructive disease (p = 0.28) with better post-transplant FEV1 (70 ± 15% versus 57 ± 11%, p = 0.02) in restrictive disease.

Conclusions

Performing two single-lung transplantations from one donor can be performed safely with encouraging intermediate-term outcome and good functional capacity. Lung twinning maximizes the donor pool and may help to overcome severe organ shortage.

Clinical trials

This research is not a clinical trial. Thus no registration details will be provided.
The additional value of 18F-FDG PET/CT imaging in guiding the treatment strategy of non-tuberculous mycobacterial patients
Authors: Chen Donghe , Chen Yunbo , Yang Shuye , Liu Kanfeng , Wang Zhen , Zhang Tingting , Wang Guolin , Zhao Kui , Su Xinhui
Published: March 2024

Objectives

Non-tuberculous mycobacteria (NTM) infection is an increasing health problem due to delaying an effective treatment. However, there are few data on 18F-FDG PET/CT for evaluating the status of NTM patients. The aim of this study was to investigate the potential value of 18F-FDG PET/CT in guiding the treatment strategy of NTM patients.

Methods

We retrospectively analyzed the cases of 23 NTM patients who underwent 18F-FDG PET/CT. The clinical data, including immune status and severity of NTM pulmonary disease (NTM-PD), were reviewed. The metabolic parameters of 18F-FDG included maximum standardized uptake value (SUVmax), SUVmax of the most FDG-avid lesion (SUVTop), SUVTop/SUVmax of the liver (SURLiver), SUVTop/SUVmax of the blood (SURBlood), metabolic lesion volume (MLV), and total lesion glycolysis (TLG). The optimal cut-off values of these parameters were determined using receiver operating characteristic curves.

Results

There were 6 patients (26.09%) with localized pulmonary diseases and 17 patients (73.91%) with disseminated diseases. The NTM lesions had high or moderate 18F-FDG uptake (median SUVTop: 8.2 ± 5.7). As for immune status, the median SUVTop in immunocompromised and immunocompetent patients were 5.2 ± 2.5 and 10.0 ± 6.4, respectively, with a significant difference (P = 0.038). As for extent of lesion involvement, SURLiver and SURBlood in localized pulmonary and disseminated diseases were 1.9 ± 1.1 vs. 3.8 ± 1.6, and 2.7 ± 1.8 vs. 5.5 ± 2.6, respectively, with a significant difference (P = 0.016 and 0.026). Moreover, for disease severity, SUVmax of the lung lesion (SUVI−lung) and SUVmax of the marrow (SUVMarrow) in the severe group were 7.7 ± 4.3 and 4.4 ± 2.7, respectively, significantly higher than those in the non-severe group (4.4 ± 2.0 and 2.4 ± 0.8, respectively) (P = 0.027 and 0.036). The ROC curves showed that SUVTop, SURLiver, SURBlood, SUVI−lung, and SUVMarrow had a high sensitivity and specificity for the identification of immune status, lesion extent, and severity of disease in NTM patients.

Conclusion

18F-FDG PET/CT is a useful tool in the diagnosis, evaluation of disease activity, immune status, and extent of lesion involvement in NTM patients, and can contribute to planning the appropriate treatment for NTM.
Lung tissue expression of epithelial injury markers is associated with acute lung injury severity but does not discriminate sepsis from ARDS
Authors: de Souza Xavier Costa Natália , da Costa Sigrist Giovana , Schalch Alexandre Santos , Belotti Luciano , Dolhnikoff Marisa , da Silva Luiz Fernando Ferraz
Published: March 2024

Background

Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in critically ill patients, and diffuse alveolar damage (DAD) is considered its histological hallmark. Sepsis is one of the most common aetiology of ARDS with the highest case-fatality rate. Identifying ARDS patients and differentiate them from other causes of acute respiratory failure remains a challenge. To address this, many studies have focused on identifying biomarkers that can help assess lung epithelial injury. However, there is scarce information available regarding the tissue expression of these markers. Evaluating the expression of elafin, RAGE, and SP-D in lung tissue offers a potential bridge between serological markers and the underlying histopathological changes. Therefore, we hypothesize that the expression of epithelial injury markers varies between sepsis and ARDS as well as according to its severity.

Methods

We compared the post-mortem lung tissue expression of the epithelial injury markers RAGE, SP-D, and elafin of patients that died of sepsis, ARDS, and controls that died from non-pulmonary causes. Lung tissue was collected during routine autopsy and protein expression was assessed by immunohistochemistry. We also assessed the lung injury by a semi-quantitative analysis.

Results

We observed that all features of DAD were milder in septic group compared to ARDS group. Elafin tissue expression was increased and SP-D was decreased in the sepsis and ARDS groups. Severe ARDS expressed higher levels of elafin and RAGE, and they were negatively correlated with PaO2/FiO2 ratio, and positively correlated with bronchopneumonia percentage and hyaline membrane score. RAGE tissue expression was negatively correlated with mechanical ventilation duration in both ARDS and septic groups. In septic patients, elafin was positively correlated with ICU admission length, SP-D was positively correlated with serum lactate and RAGE was correlated with C-reactive protein.

Conclusions

Lung tissue expression of elafin and RAGE, but not SP-D, is associated with ARDS severity, but does not discriminate sepsis patients from ARDS patients.
Malaria infection among adults residing in a highly endemic region from the Democratic Republic of the Congo
Authors: Kayiba Nadine Kalenda , Nitahara Yuko , Tshibangu-Kabamba Evariste , Mbuyi Denis Kalambayi , Kabongo-Tshibaka Augustin , Kalala Nestor Tshituka , Tshiebue Barthélemy Mukenga , Candray-Medina Katherine-Sofia , Kaku Natsuko , Nakagama Yu , Speybroeck Niko , Mumba Dieudonné Ngoyi , Disashi Ghislain Tumba , Kaneko Akira , Kido Yasutoshi
Published: March 2024

Background

Adults infected withPlasmodiumspp. in endemic areas need to be re-evaluated in light of global malaria elimination goals. They potentially undermine malaria interventions but remain an overlooked aspect of public health strategies.

Methods

This study aimed to estimate the prevalence ofPlasmodiumspp. infections, to identify underlying parasite species, and to assess predicting factors among adults residing in an endemic area from the Democratic Republic of Congo (DRC). A community-based cross-sectional survey in subjects aged 18 years and above was therefore carried out. Study participants were interviewed using a standard questionnaire and tested forPlasmodiumspp. using a rapid diagnostic test and a nested polymerase chain reaction assay. Logistic regression models were fitted to assess the effect of potential predictive factors for infections with differentPlasmodiumspp.

Results

Overall, 420 adults with an estimated prevalence ofPlasmodiumspp. infections of 60.2% [95% CI 55.5; 64.8] were included. Non-falciparumspecies infected 26.2% [95% CI 22.2; 30.5] of the study population. Among infected participants, three parasite species were identified, includingPlasmodium falciparum(88.5%),Plasmodium malariae(39.9%), andPlasmodium ovale(7.5%) but noPlasmodium vivax. Mixed species accounted for 42.3% of infections while single-species infections predominated withP. falciparum(56.5%) among infected participants. All infected participants were asymptomatic at the time of the survey. Adults belonging to the “most economically disadvantaged” households had increased risks of infections with anyPlasmodiumspp. (adjusted odds ratio, aOR = 2.87 [95% CI 1.66, 20.07]; p < 0.001), compared to those from the "less economically disadvantaged” households. Conversely, each 1 year increase in age reduced the risk of infections with anyPlasmodiumspp. (aOR = 0.99 [95% CI 0.97, 0.99]; p = 0.048). Specifically for non-falciparumspp., males had increased risks of infection than females (aOR = 1.83 [95% CI 1.13, 2.96]; p = 0.014).

Conclusion

Adults infected with malaria constitute a potentially important latent reservoir for the transmission of the disease in the study setting. They should specifically be taken into account in public health measures and translational research.
Bigger problems from smaller colonies: emergence of antibiotic-tolerant small colony variants of Mycobacterium avium complex in MAC-pulmonary disease patients
Authors: Park Hyun-Eui , Kim Kyu-Min , Trinh Minh Phuong , Yoo Jung-Wan , Shin Sung Jae , Shin Min-Kyoung
Published: March 2024

Background

Mycobacterium avium complex (MAC) is a group of slow-growing mycobacteria that includes Mycobacterium avium and Mycobacterium intracellulare. MAC pulmonary disease (MAC-PD) poses a threat to immunocompromised individuals and those with structural pulmonary diseases worldwide. The standard treatment regimen for MAC-PD includes a macrolide in combination with rifampicin and ethambutol. However, the treatment failure and disease recurrence rates after successful treatment remain high.

Results

In the present study, we investigated the unique characteristics of small colony variants (SCVs) isolated from patients with MAC-PD. Furthermore, revertant (RVT) phenotype, emerged from the SCVs after prolonged incubation on 7H10 agar. We observed that SCVs exhibited slower growth rates than wild-type (WT) strains but had higher minimum inhibitory concentrations (MICs) against multiple antibiotics. However, some antibiotics showed low MICs for the WT, SCVs, and RVT phenotypes. Additionally, the genotypes were identical among SCVs, WT, and RVT. Based on the MIC data, we conducted time-kill kinetic experiments using various antibiotic combinations. The response to antibiotics varied among the phenotypes, with RVT being the most susceptible, WT showing intermediate susceptibility, and SCVs displaying the lowest susceptibility.

Conclusions

In conclusion, the emergence of the SCVs phenotype represents a survival strategy adopted by MAC to adapt to hostile environments and persist during infection within the host. Additionally, combining the current drugs in the treatment regimen with additional drugs that promote the conversion of SCVs to RVT may offer a promising strategy to improve the clinical outcomes of patients with refractory MAC-PD.
The acute effect of a β-glucan-enriched oat bread on gastric emptying, GLP-1 response, and postprandial glycaemia and insulinemia: a randomised crossover trial in healthy adults
Authors: Revheim Ingrid , Ballance Simon , Standal Adelheid Fretland , Rieder Anne , Dierkes Jutta , Buyken Anette E. , Gilja Odd Helge , Hausken Trygve , Rosendahl-Riise Hanne
Published: March 2024

Background

The cereal fibre β-glucan reduces postprandial glycaemia, however, the underlying mechanisms are not fully understood. Thus, the aim of this study was to investigate the acute effect of a β-glucan-enriched oat bread on gastric emptying half-time (T1/2), gastric emptying lag phase (Tlag), and gastric emptying rate (GER), and the secretion of glucagon-like peptide-1 (GLP-1) as potential means to influence postprandial glycaemia.

Methods

A randomised crossover trial was conducted in 22 healthy adults (age 24.6 ± 3.1 years, BMI 23.1 ± 2.7 kg/m2) receiving 25 g available carbohydrates from a β-glucan-enriched oat bread or a control whole-wheat bread at two non-consecutive days. T1/2, Tlag, and GER were determined based on ultrasound measures of the cross-sectional gastric antrum area in the fasting state and 15, 30, 45, 60, 90, and 120 min postprandially. Capillary glucose, serum insulin, and plasma GLP-1 concentrations were measured at the same time points.

Results

A biphasic pattern of gastric emptying with a distinct Tlag before the commencement of emptying was observed in most subjects for both bread types. While no differences in GER were evident (p = 0.562), consumption of the oat bread significantly increased T1/2 by 18 min and Tlag by 14 min compared with the whole-wheat bread (p = 0.005 and p = 0.010, respectively). In addition, the oat bread significantly reduced iAUC2h for glucose and insulin responses compared with the whole-wheat bread (p = 0.001 and p < 0.001, respectively). There were no significant differences in GLP-1 response between the two breads (p = 0.892).

Conclusion

The increased T1/2 and Tlag could offer a potential mechanism for the observed attenuation of postprandial glycaemia and insulinemia after consumption of the β-glucan-enriched oat bread compared with the whole-wheat bread.

Trial registration: The study is registered at clinicaltrails.gov (NCT04571866).
mir-150-5p inhibits the osteogenic differentiation of bone marrow-derived mesenchymal stem cells by targeting irisin to regulate the p38/MAPK signaling pathway
Authors: Qi Jia-long , Zhang Zhi-dong , Dong Zhou , Shan Tao , Yin Zong-sheng
Published: March 2024

Purpose

To study the effect of miR-150-5p on the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs), and further explore the relationship between its regulatory mechanism and irisin.

Methods

We isolated mouse BMSCs, and induced osteogenic differentiation by osteogenic induction medium. Using qPCR to detect the expression of osteogenic differentiation-related genes, western blot to detect the expression of osteogenic differentiation-related proteins, and luciferase reporter system to verify that FNDC5 is the target of miR-150-5p. Irisin intraperitoneal injection to treat osteoporosis in mice constructed by subcutaneous injection of dexamethasone.

Results

Up-regulation of miR-150-5p inhibited the proliferation of BMSCs, and decreased the content of osteocalcin, ALP activity, calcium deposition, the expression of osteogenic differentiation genes (Runx2, OSX, OCN, OPN, ALP and BMP2) and protein (BMP2, OCN, and Runx2). And down-regulation of miR-150-5p plays the opposite role of up-regulation of miR-150-5p on osteogenic differentiation of BMSCs. Results of luciferase reporter gene assay showed that FNDC5 gene was the target gene of miR-150-5p, and miR-150-5p inhibited the expression of FNDC5 in mouse BMSCs. The expression of osteogenic differentiation genes and protein, the content of osteocalcin, ALP activity and calcium deposition in BMSCs co-overexpressed by miR-150-5p and FNDC5 was significantly higher than that of miR-150-5p overexpressed alone. In addition, the overexpression of FNDC5 reversed the blocked of p38/MAPK pathway by the overexpression of miR-150-5p in BMSCs. Irisin, a protein encoded by FNDC5 gene, improved symptoms in osteoporosis mice through intraperitoneal injection, while the inhibitor of p38/MAPK pathway weakened this function of irisin.

Conclusion

miR-150-5p inhibits the osteogenic differentiation of BMSCs by targeting irisin to regulate the/p38/MAPK signaling pathway, and miR-150-5p/irisin/p38 pathway is a potential target for treating osteoporosis.
Evaluation of the offset static rope evacuation procedure: insights from a safe job analysis
Authors: Abrahamsen Eirik Bjorheim , Mattingsdal Håvard , Abrahamsen Håkon Bjorheim
Published: March 2024

Background

Recently, the Norwegian Helicopter Emergency Medical Service (HEMS) has developed a procedure for a special type of static rope rescue operation, referred to as the offset technique. In this technique, the helicopter is offset from the accident site, and the HEMS technical crew member uses an offset throw line to gain access to the scene. Today, there is little practical experience of such operations, and a need has been identified for more knowledge on the potential hazards encountered during this type of operation. Such knowledge is of importance for further development of the procedure for the offset technique.

Objective

To identify potential hazards for helicopter rescue operations using the static rope offset technique and, thereby, to improve the procedure for such operations. This may lead to improved safety for patients and crew members during offset rescue operations.

Method

A Safe Job Analysis was used to identify the hazards of offset rescue operations. Such operations are divided into tasks and sub-tasks. For each sub-task, we identified potential hazards and suggested ways of preventing these.

Results

Through the Safe Job Analysis, we suggest some changes in the existing procedure for the offset technique, to make it more robust against potential hazards.

Conclusion

We have demonstrated the value of Safe Job Analysis for improving the static rope offset evacuation procedure. Our analysis has led to some changes in the procedure for offset rescue operations. This is the importance of having two throw lines and focusing on “why” in the procedure.
Four chemometric models enhanced by Latin hypercube sampling design for quantification of anti-COVID drugs: sustainability profiling through multiple greenness, carbon footprint, blueness, and whiteness metrics
Authors: Katamesh Noha S. , Abbas Ahmed Emad F. , Mahmoud Shimaa A.
Published: March 2024

Montelukast sodium (MLK) and Levocetirizine dihydrochloride (LCZ) are widely prescribed medications with promising therapeutic potential against COVID-19. However, existing analytical methods for their quantification are unsustainable, relying on toxic solvents and expensive instrumentation. Herein, we pioneer a green, cost-effective chemometrics approach for MLK and LCZ analysis using UV spectroscopy and intelligent multivariate calibration. Following a multilevel multifactor experimental design, UV spectral data was acquired for 25 synthetic mixtures and modeled via classical least squares (CLS), principal component regression (PCR), partial least squares (PLS), and genetic algorithm-PLS (GA-PLS) techniques. Latin hypercube sampling (LHS) strategically constructed an optimal validation set of 13 mixtures for unbiased predictive performance assessment. Following optimization of the models regarding latent variables (LVs) and wavelength region, the optimum root mean square error of cross-validation (RMSECV) was attained at 2 LVs for the 210–400 nm spectral range (191 data points). The GA-PLS model demonstrated superb accuracy, with recovery percentages (R%) from 98 to 102% for both analytes, and root mean square error of calibration (RMSEC) and prediction (RMSEP) of (0.0943, 0.1872) and (0.1926, 0.1779) for MLK and LCZ, respectively, as well bias-corrected mean square error of prediction (BCMSEP) of -0.0029 and 0.0176, relative root mean square error of prediction (RRMSEP) reaching 0.7516 and 0.6585, and limits of detection (LOD) reaching 0.0813 and 0.2273 for MLK and LCZ respectively. Practical pharmaceutical sample analysis was successfully confirmed via standard additions. We further conducted pioneering multidimensional sustainability evaluations using state-of-the-art greenness, blueness, and whiteness tools. The method demonstrated favorable environmental metrics across all assessment tools. The obtained Green National Environmental Method Index (NEMI), and Complementary Green Analytical Procedure Index (ComplexGAPI) quadrants affirmed green analytical principles. Additionally, the method had a high Analytical Greenness Metric (AGREE) score (0.90) and a low carbon footprint (0.021), indicating environmental friendliness. We also applied blueness and whiteness assessments using the high Blue Applicability Grade Index (BAGI) and Red–Green–Blue 12 (RGB 12) algorithms. The high BAGI (90) and RGB 12 (90.8) scores confirmed the method's strong applicability, cost-effectiveness, and sustainability. This work puts forward an optimal, economically viable green chemistry paradigm for pharmaceutical quality control aligned with sustainable development goals.
New insights into the molecular phylogeny, biogeographical history, and diversification of Amblyomma ticks (Acari: Ixodidae) based on mitogenomes and nuclear sequences
Authors: Uribe Juan E. , Kelava Samuel , Nava Santiago , Cotes-Perdomo Andrea P. , Castro Lyda R. , Rivera-Paéz Fredy A. , Perea Silvia , Mans Ben J. , Gofton Alexander , Teo Ernest J. M. , Zardoya Rafael , Barker Stephen C.
Published: March 2024

Background

Amblyomma is the third most diversified genus of Ixodidae that is distributed across the Indomalayan, Afrotropical, Australasian (IAA), Nearctic and Neotropical biogeographic ecoregions, reaching in the Neotropic its highest diversity. There have been hints in previously published phylogenetic trees from mitochondrial genome, nuclear rRNA, from combinations of both and morphology that the Australasian Amblyomma or the Australasian Amblyomma plus the Amblyomma species from the southern cone of South America, might be sister-group to the Amblyomma of the rest of the world. However, a stable phylogenetic framework of Amblyomma for a better understanding of the biogeographic patterns underpinning its diversification is lacking.

Methods

We used genomic techniques to sequence complete and nearly complete mitochondrial genomes –ca. 15 kbp– as well as the nuclear ribosomal cluster –ca. 8 kbp– for 17 Amblyomma ticks in order to study the phylogeny and biogeographic pattern of the genus Amblyomma, with particular emphasis on the Neotropical region. The new genomic information generated here together with genomic information available on 43 ticks (22 other Amblyomma species and 21 other hard ticks–as outgroup–) were used to perform probabilistic methods of phylogenetic and biogeographic inferences and time-tree estimation using biogeographic dates.

Results

In the present paper, we present the strongest evidence yet that Australasian Amblyomma may indeed be the sister-group to the Amblyomma of the rest of the world (species that occur mainly in the Neotropical and Afrotropical zoogeographic regions). Our results showed that all Amblyomma subgenera (Cernyomma, Anastosiella, Xiphiastor, Adenopleura, Aponomma and Dermiomma) are not monophyletic, except for Walkeriana and Amblyomma. Likewise, our best biogeographic scenario supports the origin of Amblyomma and its posterior diversification in the southern hemisphere at 47.8 and 36.8 Mya, respectively. This diversification could be associated with the end of the connection of Australasia and Neotropical ecoregions by the Antarctic land bridge. Also, the biogeographic analyses let us see the colonization patterns of some neotropical Amblyomma species to the Nearctic.

Conclusions

We found strong evidence that the main theater of diversification of Amblyomma was the southern hemisphere, potentially driven by the Antarctic Bridge's intermittent connection in the late Eocene. In addition, the subgeneric classification of Amblyomma lacks evolutionary support. Future studies using denser taxonomic sampling may lead to new findings on the phylogenetic relationships and biogeographic history of Amblyomma genus.

Graphical Abstract
Accelerating targeted mosquito control efforts through mobile West Nile virus detection
Authors: Varga Zsaklin , Bueno-Marí Rubén , Risueño Iranzo José , Kurucz Kornélia , Tóth Gábor Endre , Zana Brigitta , Zeghbib Safia , Görföl Tamás , Jakab Ferenc , Kemenesi Gábor
Published: March 2024

Background

Different mosquito control strategies have been implemented to mitigate or prevent mosquito-related public health situations. Modern mosquito control largely relies on multiple approaches, including targeted, specific treatments. Given this, it is becoming increasingly important to supplement these activities with rapid and mobile diagnostic capacities for mosquito-borne diseases. We aimed to create and test the applicability of a rapid diagnostic system for West Nile virus that can be used under field conditions.

Methods

In this pilot study, various types of adult mosquito traps were applied within the regular mosquito monitoring activity framework for mosquito control. Then, the captured specimens were used for the detection of West Nile virus RNA under field conditions with a portable qRT-PCR approach within 3–4 h. Then, positive samples were subjected to confirmatory RT-PCR or NGS sequencing in the laboratory to obtain genome information of the virus. We implemented phylogenetic analysis to characterize circulating strains.

Results

A total of 356 mosquito individuals representing 7 species were processed in 54 pools, each containing up to 20 individuals. These pools were tested for the presence of West Nile virus, and two pools tested positive, containing specimens from the Culex pipiens and Anopheles atroparvus mosquito species. As a result of subsequent sequencing, we present the complete genome of West Nile virus and Bagaza virus.

Conclusions

The rapid identification of infected mosquitoes is the most important component of quick response adulticide or larvicide treatments to prevent human cases. The conceptual framework of real-time surveillance can be optimized for other pathogens and situations not only in relation to West Nile virus. We present an early warning system for mosquito-borne diseases and demonstrate its application to aid rapid-response mosquito control actions.

Graphical Abstract
Intact lung tissue and bronchoalveolar lavage fluid are both suitable for the evaluation of murine lung microbiome in acute lung injury
Authors: Zheng Lijun , Liu Chengjun , Wang Hongjing , Zhang Jun , Mao Lejiao , Dong Xiaomei , Hu Siyao , Li Na , Pi Dandan , Qiu Jingfu , Xu Feng , Chen Chengzhi , Zou Zhen
Published: March 2024

Background

Accumulating clinical evidence suggests that lung microbiome is closely linked to the progression of pulmonary diseases; however, it is still controversial which specimen type is preferred for the evaluation of lung microbiome.

Methods and results

To address this issue, we established a classical acute lung injury (ALI) mice model by intratracheal instillation of lipopolysaccharides (LPS). We found that the bacterial DNA obtained from the bronchoalveolar lavage fluid (BALF), intact lung tissue [Lung(i)], lung tissue after perfused [Lung(p)], and feces of one mouse were enough for 16S rRNA sequencing, except the BALF of mice treated with phosphate buffer saline (PBS), which might be due to the biomass of lung microbiome in the BALF were upregulated in the mice treated with LPS. Although the alpha diversity among the three specimens from lungs had minimal differences, Lung(p) had higher sample-to-sample variation compared with BALF and Lung(i). Consistently, PCoA analysis at phylum level indicated that BALF was similar to Lung(i), but not Lung(p), in the lungs of mice treated with LPS, suggesting that BALF and Lung(i) were suitable for the evaluation of lung microbiome in ALI. Importantly, Actinobacteria and Firmicutes were identified as the mostly changed phyla in the lungs and might be important factors involved in the gut-lung axis in ALI mice. Moreover, Actinobacteria and Proteobacteria might play indicative roles in the severity of lung injury.

Conclusion

This study shows both Lung(i) and BALF are suitable for the evaluation of murine lung microbiome in ALI, and several bacterial phyla, such as Actinobacteria, may serve as potential biomarkers for the severity of ALI.
Harmonizing culture and consumer psychology: optimizing color schemes for children’s product design inspired by traditional ornaments
Authors: Liang Ling Lin , Hangeldiyeva Nazik
Published: March 2024

Color is one of the vital components of product design and the choice of color combination is a critical factor that affects consumer reaction and purchase decisions. However, the impact of traditional colors on color extraction and product design has seldom been studied. The purpose of this study is to discover suitable colors from traditional patterns to create color schemes that will be used in the design of children’s products. Colors were extracted from five major traditional ornaments obtained from Turkmenistan’s national carpets, each representing one of the main Turkmen tribes, using tools like Photoshop, Adobe Color, and EasyRGB, with the objective of investigating psychological-emotional attachment, reaction, and attitudes towards the colors obtained. This initial extraction provided 124 color data points. Initially, extracted colors were refined and used to develop novel color schemes by two independent survey studies. The first survey, based on a sample of 104 parents of preschool children, identified colors that have a positive emotional effect on consumer preferences and provided the basis to develop color schemes. As a result, 25 colors were identified for use in developing 14 color schemes. The second survey, based on a sample of 48 parents of preschool children, identified which color schemes have an attraction for consumers. The survey indicated that 11 out of these 14 schemes were highly favored by the respondents. Based on these results, this study proposed new color schemes for children’s products, extracted from traditional patterns of Turkmenistan and aligned with the psychological perception of the consumers.