bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhaledversussystemic corticosteroids for acute exacerbations of COPD: a systematic review and meta-analysis
Authors: Papadopoulou Efthymia , Bin Safar Sulaiman , Khalil Ali , Hansel Jan , Wang Ran , Corlateanu Alexandru , Kostikas Konstantinos , Tryfon Stavros , Vestbo Jørgen , Mathioudakis Alexander G.
Published: March 2024

This meta-analysis compares the efficacy and safety of inhaledversussystemic corticosteroids for COPD exacerbations.

Following a pre-registered protocol, we appraised eligible randomised controlled trials (RCTs) according to Cochrane methodology, performed random-effects meta-analyses for all outcomes prioritised in the European Respiratory Society COPD core outcome set and rated the certainty of evidence as per Grading of Recommendations Assessment, Development and Evaluation methodology.

We included 20 RCTs totalling 2140 participants with moderate or severe exacerbations. All trials were at high risk of methodological bias. Low-certainty evidence did not reveal significant differences between inhaled and systemic corticosteroids for treatment failure rate (relative risk 1.75, 95% CI 0.76–4.02, n=569 participants); breathlessness (mean change: standardised mean difference (SMD) −0.11, 95% CI −0.36–0.15, n=239; post-treatment scores: SMD −0.18, 95% CI −0.41–0.05, n=293); serious adverse events (relative risk 1.47, 95% CI 0.56–3.88, n=246); or any other efficacy outcomes. Moderate-certainty evidence implied a tendency for fewer adverse events with inhaled compared to systemic corticosteroids (relative risk 0.80, 95% CI 0.64–1.0, n=480). Hyperglycaemia and oral fungal infections were observed more frequently with systemic and inhaled corticosteroids, respectively.

Limited available evidence suggests potential noninferiority of inhaled to systemic corticosteroids in COPD exacerbations. Appropriately designed and powered RCTs are warranted to confirm these findings.
Nocturnal oxygen therapy in obstructive sleep apnoea: a systematic review and meta-analysis
Authors: Phyu Su Latt , Ercan Selin , Harriss Eli , Turnbull Christopher
Published: March 2024

Obstructive sleep apnoea is characterised by recurrent reduction of airflow during sleep leading to intermittent hypoxia. Continuous positive airway pressure is the first-line treatment but is limited by poor adherence. Nocturnal oxygen therapy may be an alternative treatment for obstructive sleep apnoea but its effects remain unclear. This meta-analysis evaluates the effects of nocturnal oxygen therapy on both obstructive sleep apnoea severity and blood pressure.

A literature search was performed based on the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. Peer-reviewed, randomised studies that compared the effect of nocturnal oxygen therapy to sham in obstructive sleep apnoea patients were included. The main outcomes were the apnoea–hypopnoea index and systolic and diastolic blood pressure.

The search strategy yielded 1295 citations. Nine studies with 502 participants were included. When nocturnal oxygen therapy was compared to sham/air, it significantly reduced the apnoea–hypopnoea index (mean difference (MD) −15.17 events·h−1, 95% CI −19.95– −10.38 events·h−1, p<0.00001). Nocturnal oxygen therapy had no significant effect on blood pressure at follow-up without adjustment for baseline values, but did, where available, significantly attenuate the change in blood pressure from baseline to follow-up for both systolic blood pressure (MD −2.79 mmHg, 95% CI −5.45– −0.14 mmHg, p=0.040) and diastolic blood pressure (MD −2.20 mmHg, 95% CI −3.83– −0.57 mmHg, p=0.008).

Nocturnal oxygen therapy reduced the apnoea–hypopnoea index severity and the change in (but not absolute) systolic and diastolic blood pressure, compared to sham. This suggests that nocturnal oxygen therapy may be a treatment option for obstructive sleep apnoea. Further studies with longer-term follow-up and standardised measurements are needed.
Copper-Free Resin-Based Braking Materials: A New Approach for Substituting Copper with Fly-Ash Cenospheres in Composites
Authors: Zheng Kaikui , Lin Youxi , You Shanmin , Ren Zhiying , Huang Jianmeng
Published: March 2024

Copper particles emitted from braking have become a significant source of environmental pollution. However, copper plays a crucial role in resin-based braking materials. Developing high-performance braking materials without copper has become a significant challenge. In this paper, the resin-based braking materials were filled with fly-ash cenospheres to develop copper-free braking materials. The effects of fly-ash cenospheres on the physical properties, mechanical and friction and wear properties of braking materials were studied. Furthermore, the wear mechanism of copper-free resin-based braking materials filled with fly-ash cenospheres was discussed. The results indicate that the inclusion of fly-ash cenospheres in the braking materials improved their thermal stability, hardness and impact strength, reduced their density, effectively increased the friction coefficient at medium and high temperatures, and enhanced the heat-fade resistance of the braking materials. The inclusion of fly-ash cenospheres contributed to the formation of surface friction film during the friction process of the braking materials, and facilitated the transition of form from abrasive wear to adhesive wear. At 100–350 ℃, the friction coefficient of the optimal formulation is in the range of 0.57–0.61, and the wear rate is in the range (0.29–0.65) × 10−7 cm3·N−1·m−1, demonstrating excellent resistance to heat-fade and stability in friction coefficient. This research proposes the use of fly-ash cenospheres as a substitute for environmentally harmful and expensive copper in brake materials, which not only improves the performance of braking materials but also reduces their costs.
Comparative plastome analysis of the sister genera Ceratocephala and Myosurus (Ranunculaceae) reveals signals of adaptive evolution to arid and aquatic environments
Authors: Long Jing , He Wen-Chuang , Peng Huan-Wen , Erst Andrey S. , Wang Wei , Xiang Kun-Li
Published: March 2024

Background

Expansion and contraction of inverted repeats can cause considerable variation of plastid genomes (plastomes) in angiosperms. However, little is known about whether structural variations of plastomes are associated with adaptation to or occupancy of new environments. Moreover, adaptive evolution of angiosperm plastid genes remains poorly understood. Here, we sequenced the complete plastomes for four species of xerophytic Ceratocephala and hydrophytic Myosurus, as well as Ficaria verna. By an integration of phylogenomic, comparative genomic, and selection pressure analyses, we investigated evolutionary patterns of plastomes in Ranunculeae and their relationships with adaptation to dry and aquatic habitats.

Results

Owing to the significant contraction of the boundary of IRA/LSC towards the IRA, plastome sizes and IR lengths of Myosurus and Ceratocephala are smaller within Ranunculeae. Compared to other Ranunculeae, the Myosurus plastome lost clpP and rps16, one copy of rpl2 and rpl23, and one intron of rpoC1 and rpl16, and the Ceratocephala plastome added an infA gene and lost one copy of rpl2 and two introns of clpP. A total of 11 plastid genes (14%) showed positive selection, two genes common to Myosurus and Ceratocephala, seven in Ceratocephala only, and two in Myosurus only. Four genes showed strong signals of episodic positive selection. The rps7 gene of Ceratocephala and the rpl32 and ycf4 genes of Myosurus showed an increase in the rate of variation close to 3.3 Ma.

Conclusions

The plastomic structure variations as well as the positive selection of two plastid genes might be related to the colonization of new environments by the common ancestor of Ceratocephala and Myosurus. The seven and two genes under positive selection might be related to the adaptation to dry and aquatic habitats in Ceratocephala and Myosurus, respectively. Moreover, intensified aridity and frequent sea-level fluctuations, as well as global cooling, might have favored an increased rate of change in some genes at about 3.3 Ma, associated with adaptation to dry and aquatic environments, respectively. These findings suggest that changing environments might have influenced structural variations of plastomes and fixed new mutations arising on some plastid genes owing to adaptation to specific habitats.
Diabetes mellitus and idiopathic pulmonary fibrosis: a Mendelian randomization study
Authors: Kang Quou , Ren Jing , Cong Jinpeng , Yu Wencheng
Published: March 2024

Background

The question as to whether or not diabetes mellitus increases the risk of idiopathic pulmonary fibrosis (IPF) remains controversial. This study aimed to investigate the causal association between type 1 diabetes (T1D), type 2 diabetes (T2D), and IPF using Mendelian randomization (MR) analysis.

Methods

We used two-sample univariate and multivariate MR (MVMR) analyses to investigate the causal relationship between T1D or T2D and IPF. We obtained genome-wide association study (GWAS) data for T1D and T2D from the European Bioinformatics Institute, comprising 29,652 T1D samples and 101,101 T1D single nucleotide polymorphisms (SNPs) and 655,666 T2D samples and 5,030,727 T2D SNPs. We also used IPF GWAS data from the FinnGen Biobank comprising 198,014 IPF samples and 16,380,413 IPF SNPs. All cases and controls in these datasets were derived exclusively from European populations. In the univariate MR analysis, we employed inverse variance-weighted (IVW), weighted median (WM), and MR-Egger regression methods. For the MVMR analysis, we used the multivariate IVW method primarily, and supplemented it with multivariate MR-Egger and multivariate MR- least absolute shrinkage and selection operator methods. Heterogeneity tests were conducted using the MR-IVW and MR-Egger regression methods, whereas pleiotropic effects were assessed using the MR-Egger intercept. The results of MR and sensitivity analyses were visualized using forest, scatter, leave-one-out, and funnel plots.

Results

Univariate MR revealed a significant causal relationship between T1D and IPF (OR = 1.118, 95% CI = 1.021–1.225, P = 0.016); however, no significant causal relationship was found between T2D and IPF (OR = 0.911, 95% CI = 0.796–1.043, P = 0.178). MVMR analysis further confirmed a causal association between T1D and IPF (OR = 1.133, 95% CI = 1.011–1.270, P = 0.032), but no causal relationship between T2D and IPF (OR = 1.009, 95% CI = 0.790–1.288, P = 0.950). Sensitivity analysis results validated the stability and reliability of our findings.

Conclusion

Univariate and multivariate analyses demonstrated a causal relationship between T1D and IPF, whereas no evidence was found to support a causal relationship between T2D and IPF. Therefore, in clinical practice, patients with T1D should undergo lung imaging for early detection of IPF.
Do women living in a deprived neighborhood have higher maternity care costs and worse pregnancy outcomes? A retrospective population-based study
Authors: Nanninga Eline K. , Menting Malou D. , van der Hijden Eric J. E. , Portrait France R. M.
Published: March 2024

Background

Living in a deprived neighborhood is associated with poorer health, due to factors such as lower socio-economic status and an adverse lifestyle. There is little insight into whether living in deprived neighborhood is associated with adverse maternity care outcomes and maternity health care costs. We expect women in a deprived neighborhood to experience a more complicated pregnancy, with more secondary obstetric care (as opposed to primary midwifery care) and higher maternity care costs. This study aimed to answer the following research question: to what extent are moment of referral from primary to secondary care, mode of delivery, (extreme or very) preterm delivery and maternity care costs associated with neighborhood deprivation?

Methods

This retrospective cohort study used a national Dutch database with healthcare claims processed by health insurers. All pregnancies that started in 2018 were included. The moment of referral from primary to secondary care, mode of delivery, (extreme or very) preterm delivery and maternity care costs were compared between women in deprived and non-deprived neighborhoods. We reported descriptive statistics, and results of ordinal logistic, multinomial and linear regressions to assess whether differences between the two groups exist.

Results

Women in deprived neighborhoods had higher odds of being referred from primary to secondary care during pregnancy (adjusted OR 1.49, 95%CI 1.41–1.57) and to start their pregnancy in secondary care (adjusted OR 1.55, 95%CI 1.44–1.66). Furthermore, women in deprived neighborhoods had lower odds of assisted delivery than women in non-deprived neighborhoods (adjusted OR 0.73, 95%CI 0.66–0.80), and they had higher odds of a cesarean section (adjusted OR 1.19, 95%CI 1.13–1.25). On average, women in a deprived neighborhood had higher maternity care costs worth 156 euros (95%CI 104–208).

Conclusion

This study showed that living in a deprived neighborhood is associated with more intensive maternal care and higher maternal care costs in the Netherlands. These findings support the needs for greater attention to socio-economic factors in maternity care in the Netherlands.
Quality of life and work functionality in severe asthma patients: the impact of biological therapies
Authors: Leso Veruscka , Candia Claudio , Pacella Daniela , Molino Antonio , Nocera Caterina , Maniscalco Mauro , Iavicoli Ivo
Published: March 2024

Background

Severe asthma can cause poor health status, poor health-related quality of life (HRQoL) and an impaired functioning at work. However, to date, limited data are available on the impact of the biological therapies on such outcomes. Therefore, aim of the present study was to prospectively assess the clinical, quality of life and work functionality issues in severe asthma patients both at baseline and after 6 months of biological therapies and determine which individual, pathological and occupational factors can influence such parameters.

Methods

Fifty-two patients were enrolled between December 2022 and June 2023. Patients’ personal, clinical, functional and occupational features were assessed. The Short Form Health Survey (SF-12), the Work Productivity and Activity Impairment (WPAI) questionnaire and the Work Ability Index (WAI) were employed to assess HRQoL, the employee’s productivity and perception of work ability, respectively.

Results

Among the enrolled patients, 30 (57.70%) were employed. Biological therapy induced a significant improvement in clinical and functional parameters, e.g., FEV1% (72 ± 12 vs.87 ± 13%; 72 ± 14 vs. 86 ± 14%), FVC% (92 ± 11 vs. 101 ± 11%; 90 ± 13 vs. 98 ± 14%) and FEV1/FVC (62 ± 11 vs. 71 ± 8%; 64 ± 9 vs. 70 ± 8%) in workers and non-workers, respectively (P < 0.001). Comparably, the perception of life quality significantly improved, as physical and mental health scores, in the overall cohort, increased from 40.7 ± 10.3 and 48.5 ± 8.5 to 46.8 ± 8.6 and 51.6 ± 6.4, respectively (P < 0.001). The work ability perception significantly improved from a moderate to a good one (34 ± 6 vs. 40 ± 6, P = 0.001). A significant reduction in the absenteeism (19 ± 15 vs. 3 ± 11%; P < 0.001) and presenteeism rate (53 ± 24 vs. 29 ± 26%; P < 0.001), and an improvement in daily (40 ± 27.5% vs. 28.9 ± 24.7%, P < 0.001, in the overall population) and work activities (57 ± 25 vs. 29 ± 27%, P < 0.001) was determined. Gender, age, symptoms control and pulmonary functionality were correlated with the physical and mental health perception, daily activity impairment and work ability.

Conclusions

Our study pointed out that biological therapies improved clinical, general life and occupational outcomes in patients with severe asthma. The correlation between clinical aspects and psychological and occupational issues suggest the relevance for a multidisciplinary management of the disease for an effective participation of patients in the world of work.
Comprehensive evaluation of the relationship between biomarker profiles and neoadjuvant chemotherapy outcomes for breast cancer patients
Authors: Wang Mijia , Wei Zhendong , Kong Jixia , Zhao Haidong
Published: March 2024

Background

Accurately predicting the response to neoadjuvant chemotherapy (NAC) in breast cancer patients is crucial for guiding treatment strategies and enhancing clinical outcomes. Current studies have primarily focused on a limited set of biomarkers. More importantly, the results of many studies are in conflict. To address this, we conducted a comprehensive evaluation of the predictive value of a diverse range of clinically available molecular biomarkers in breast cancer, including HER2, ER, PR, TOPO II, EGFR, Ki67, CK5/6, AR, and p53. Additionally, we assessed changes in these biomarkers after NAC administration.

Methods

Our study involved 189 patients with invasive breast cancer who underwent NAC at our institute. We examined biomarker profiles in core-needle biopsies taken before NAC and in surgical specimens obtained after NAC. We examined the association between these biomarkers and NAC outcomes, focusing on two main aspects: the rate of pathological complete response (pCR) and the reduction in tumor size. We used Chi-square and Mann-Whitney U tests to compare biomarker status changes between pCR and non-pCR patients. Linear regression analysis was employed to evaluate the relationship between biomarker status and tumor shrinkage rate. Additionally, we compared the expression status of these biomarkers before and after NAC using Chi-square and Wilcoxon signed-rank tests.

Results and conclusions

Our results demonstrated significant differences in the expression levels of HER2, ER, PR, TOPO II, EGFR, and Ki67 between pCR and non-pCR patients, underscoring their potential as predictive markers for NAC outcomes. Importantly, our results have shed light on the contentious issue surrounding TOPO II in NAC outcome prediction. We have provided evidence that establishes a significantly positive association between TOPO II expression level and the pCR rate. Notably, tumor size was identified as a relevant predictive factor for achieving pCR. Regarding biomarker profiles, only Ki67 levels and TOPO II status exhibited changes following NAC, resolving previous controversies. While the ER and PR status remained unchanged, their expression values exhibited a slight but significant decrease post-NAC. Our results provide clarity and insights into the value and potential of using these biomarkers to predict NAC responses and prognosis in breast cancer patients.
Thai novice nurses’ lived experiences and perspectives of breastfeeding and human milk in the Neonatal Intensive Care Unit (NICU)
Authors: Srichalerm Tippawan , Jacelon Cynthia S. , Sibeko Lindiwe , Granger Jumpee , Briere Carrie-Ellen
Published: March 2024

Background

Breastfeeding and human milk have well-documented health benefits for newborn infants, particularly those who are sick. However, breastfeeding rates and human milk feeding among infants in neonatal intensive units (NICU) in Thailand are still low; thus, breastfeeding promotion and support are required for Thai mothers of premature infants. Newly graduated nurses can play a critical role within the healthcare support system and can have a significant impact on improving breastfeeding practices in the NICU. The objective of this study was to investigate the lived experiences and perspectives of Thai novice nurses on supporting breastfeeding and human milk feeding in the NICU.

Methods

The study was conducted between March 2021 and May 2022 at three medical centers in the central region of Thailand. This study employed a descriptive phenomenological approach to explore Thai novice nurses’ experiences and perspectives on breastfeeding. Purposive sampling was used to invite Thai novice nurses who have work experience in providing breastfeeding support to NICU mothers and their infants to participate in online interviews using a video conference platform (Zoom). Semi-structured questions were used to interview study participants in their native language. Data were analyzed using Colaizzi’s method of data analysis to identify emergent themes. Member checks, peer debriefing, and self-reflection were applied to ensure the validity and trustworthiness of the study results. Back-translation was also used as a quality and accuracy assurance.

Results

A total of thirteen novice nurses agreed to participate in the study. All were female, and their ages ranged from 21 to 24 years old at the time of the interview. The researchers identified five major themes related to the overall study objectives and research questions. They are: positive attitude toward breastfeeding and human milk, facing breastfeeding challenges at work, self-confidence rooted in experience, professional skill needs, and requiring further support.

Conclusions

Our results suggest that breastfeeding education plays a vital role in encouraging new nurses to provide breastfeeding support to mothers of preterm infants. Establishing breastfeeding support training and innovative learning strategies can be crucial in developing appropriate breastfeeding practice guidelines and policies to support Thai breastfeeding mothers in the NICU.
Cross-reactive CD8+ T cell responses to tumor-associated antigens (TAAs) and homologous microbiota-derived antigens (MoAs)
Authors: Cavalluzzo Beatrice , Viuff Marie Christine , Tvingsholm Siri Amanda , Ragone Concetta , Manolio Carmen , Mauriello Angela , Buonaguro Franco M. , Tornesello Maria Lina , Izzo Francesco , Morabito Alessandro , Hadrup Sine Reker , Tagliamonte Maria , Buonaguro Luigi
Published: March 2024

Background

We have recently shown extensive sequence and conformational homology between tumor-associated antigens (TAAs) and antigens derived from microorganisms (MoAs). The present study aimed to assess the breadth of T-cell recognition specific to MoAs and the corresponding TAAs in healthy subjects (HS) and patients with cancer (CP).

Method

A library of > 100 peptide-MHC (pMHC) combinations was used to generate DNA-barcode labelled multimers. Homologous peptides were selected from the Cancer Antigenic Peptide Database, as well as Bacteroidetes/Firmicutes-derived peptides. They were incubated with CD8 + T cells from the peripheral blood of HLA-A*02:01 healthy individuals (n = 10) and cancer patients (n = 16). T cell recognition was identified using tetramer-staining analysis. Cytotoxicity assay was performed using as target cells TAP-deficient T2 cells loaded with MoA or the paired TuA.

Results

A total of 66 unique pMHC recognized by CD8+ T cells across all groups were identified. Of these, 21 epitopes from microbiota were identified as novel immunological targets. Reactivity against selected TAAs was observed for both HS and CP. pMHC tetramer staining confirmed CD8+ T cell populations cross-reacting with CTA SSX2 and paired microbiota epitopes. Moreover, PBMCs activated with the MoA where shown to release IFNγ as well as to exert cytotoxic activity against cells presenting the paired TuA.

Conclusions

Several predicted microbiota-derived MoAs are recognized by T cells in HS and CP. Reactivity against TAAs was observed also in HS, primed by the homologous bacterial antigens. CD8+ T cells cross-reacting with MAGE-A1 and paired microbiota epitopes were identified in three subjects. Therefore, the microbiota can elicit an extensive repertoire of natural memory T cells to TAAs, possibly able to control tumor growth (“natural anti-cancer vaccination”). In addition, non-self MoAs can be included in preventive/therapeutic off-the-shelf cancer vaccines with more potent anti-tumor efficacy than those based on TAAs.
Bronchiolitis recovery and the use of High Efficiency Particulate Air (HEPA) Filters (The BREATHE Study): study protocol for a multi-center, parallel, double-blind, randomized controlled clinical trial
Authors: Cowan Kelly , Semmens Erin O. , Lee Jeannette Y. , Walker Ethan S. , Smith Paul G. , Fu Linda , Singleton Rosalyn , Cox Sara McClure , Faiella Jennifer , Chassereau Laurie , Lawrence Lora , Ying Jun , Baldner Jaime , Garza Maryam , Annett Robert , Chervinskiy Sheva K. , Snowden Jessica
Published: March 2024

Background

Acute viral bronchiolitis is the most common reason for hospitalization of infants in the USA. Infants hospitalized for bronchiolitis are at high risk for recurrent respiratory symptoms and wheeze in the subsequent year, and longer-term adverse respiratory outcomes such as persistent childhood asthma. There are no effective secondary prevention strategies. Multiple factors, including air pollutant exposure, contribute to risk of adverse respiratory outcomes in these infants. Improvement in indoor air quality following hospitalization for bronchiolitis may be a prevention opportunity to reduce symptom burden. Use of stand-alone high efficiency particulate air (HEPA) filtration units is a simple method to reduce particulate matter ≤ 2.5 µm in diameter (PM2.5), a common component of household air pollution that is strongly linked to health effects.

Methods

BREATHE is a multi-center, parallel, double-blind, randomized controlled clinical trial. Two hundred twenty-eight children < 12 months of age hospitalized for the first time with bronchiolitis will participate. Children will be randomized 1:1 to receive a 24-week home intervention with filtration units containing HEPA and carbon filters (in the child’s sleep space and a common room) or to a control group with units that do not contain HEPA and carbon filters. The primary objective is to determine if use of HEPA filtration units reduces respiratory symptom burden for 24 weeks compared to use of control units. Secondary objectives are to assess the efficacy of the HEPA intervention relative to control on (1) number of unscheduled healthcare visits for respiratory complaints, (2) child quality of life, and (3) average PM2.5 levels in the home.

Discussion

We propose to test the use of HEPA filtration to improve indoor air quality as a strategy to reduce post-bronchiolitis respiratory symptom burden in at-risk infants with severe bronchiolitis. If the intervention proves successful, this trial will support use of HEPA filtration for children with bronchiolitis to reduce respiratory symptom burden following hospitalization.

Trial registration

NCT05615870. Registered on November 14, 2022.
Predicting the presence of coronary plaques featuring high-risk characteristics using polygenic risk scores and targeted proteomics in patients with suspected coronary artery disease
Authors: Møller Peter Loof , Rohde Palle Duun , Dahl Jonathan Nørtoft , Rasmussen Laust Dupont , Nissen Louise , Schmidt Samuel Emil , McGilligan Victoria , Gudbjartsson Daniel F. , Stefansson Kari , Holm Hilma , Bentzon Jacob Fog , Bøttcher Morten , Winther Simon , Nyegaard Mette
Published: March 2024

Background

The presence of coronary plaques with high-risk characteristics is strongly associated with adverse cardiac events beyond the identification of coronary stenosis. Testing by coronary computed tomography angiography (CCTA) enables the identification of high-risk plaques (HRP). Referral for CCTA is presently based on pre-test probability estimates including clinical risk factors (CRFs); however, proteomics and/or genetic information could potentially improve patient selection for CCTA and, hence, identification of HRP. We aimed to (1) identify proteomic and genetic features associated with HRP presence and (2) investigate the effect of combining CRFs, proteomics, and genetics to predict HRP presence.

Methods

Consecutive chest pain patients (n = 1462) undergoing CCTA to diagnose obstructive coronary artery disease (CAD) were included. Coronary plaques were assessed using a semi-automatic plaque analysis tool. Measurements of 368 circulating proteins were obtained with targeted Olink panels, and DNA genotyping was performed in all patients. Imputed genetic variants were used to compute a multi-trait multi-ancestry genome-wide polygenic score (GPSMult). HRP presence was defined as plaques with two or more high-risk characteristics (low attenuation, spotty calcification, positive remodeling, and napkin ring sign). Prediction of HRP presence was performed using the glmnet algorithm with repeated fivefold cross-validation, using CRFs, proteomics, and GPSMult as input features.

Results

HRPs were detected in 165 (11%) patients, and 15 input features were associated with HRP presence. Prediction of HRP presence based on CRFs yielded a mean area under the receiver operating curve (AUC) ± standard error of 73.2 ± 0.1, versus 69.0 ± 0.1 for proteomics and 60.1 ± 0.1 for GPSMult. Combining CRFs with GPSMult increased prediction accuracy (AUC 74.8 ± 0.1 (P = 0.004)), while the inclusion of proteomics provided no significant improvement to either the CRF (AUC 73.2 ± 0.1, P = 1.00) or the CRF + GPSMult (AUC 74.6 ± 0.1, P = 1.00) models, respectively.

Conclusions

In patients with suspected CAD, incorporating genetic data with either clinical or proteomic data improves the prediction of high-risk plaque presence.

Trial registration

https://clinicaltrials.gov/ct2/show/NCT02264717 (September 2014).
scDrugPrio: a framework for the analysis of single-cell transcriptomics to address multiple problems in precision medicine in immune-mediated inflammatory diseases
Authors: Schäfer Samuel , Smelik Martin , Sysoev Oleg , Zhao Yelin , Eklund Desiré , Lilja Sandra , Gustafsson Mika , Heyn Holger , Julia Antonio , Kovács István A. , Loscalzo Joseph , Marsal Sara , Zhang Huan , Li Xinxiu , Gawel Danuta , Wang Hui , Benson Mikael
Published: March 2024

Background

Ineffective drug treatment is a major problem for many patients with immune-mediated inflammatory diseases (IMIDs). Important reasons are the lack of systematic solutions for drug prioritisation and repurposing based on characterisation of the complex and heterogeneous cellular and molecular changes in IMIDs.

Methods

Here, we propose a computational framework, scDrugPrio, which constructs network models of inflammatory disease based on single-cell RNA sequencing (scRNA-seq) data. scDrugPrio constructs detailed network models of inflammatory diseases that integrate information on cell type-specific expression changes, altered cellular crosstalk and pharmacological properties for the selection and ranking of thousands of drugs.

Results

scDrugPrio was developed using a mouse model of antigen-induced arthritis and validated by improved precision/recall for approved drugs, as well as extensive in vitro, in vivo, and in silico studies of drugs that were predicted, but not approved, for the studied diseases. Next, scDrugPrio was applied to multiple sclerosis, Crohn’s disease, and psoriatic arthritis, further supporting scDrugPrio through prioritisation of relevant and approved drugs. However, in contrast to the mouse model of arthritis, great interindividual cellular and gene expression differences were found in patients with the same diagnosis. Such differences could explain why some patients did or did not respond to treatment. This explanation was supported by the application of scDrugPrio to scRNA-seq data from eleven individual Crohn’s disease patients. The analysis showed great variations in drug predictions between patients, for example, assigning a high rank to anti-TNF treatment in a responder and a low rank in a nonresponder to that treatment.

Conclusions

We propose a computational framework, scDrugPrio, for drug prioritisation based on scRNA-seq of IMID disease. Application to individual patients indicates scDrugPrio’s potential for personalised network-based drug screening on cellulome-, genome-, and drugome-wide scales. For this purpose, we made scDrugPrio into an easy-to-use R package (https://github.com/SDTC-CPMed/scDrugPrio).
Aeromonas veronii-associated endogenous endophthalmitis: a case report
Authors: Lin Jiali , Zhong Haibin , Chen Qi , Cui Ling , Xu Fan , Tang Fen
Published: March 2024

Background

Aeromonas veronii is a very rare and highly pathogenic microorganism. We investigate the clinical characteristics and significance of endogenous endophthalmitis caused by Aeromonas veronii in our patient.

Case presentation

A 30-year-old Asian women with systemic lupus erythematosus, uremia, and hypertension developed acute infectious endophthalmitis caused by Aeromonas veronii. After emergency vitrectomy and antibiotic therapy, the clinical condition worsened requiring enucleation.

Conclusions

Aeromonas veronii can cause infection in the human eye, which can manifest as acute endophthalmitis. Early diagnosis and targeted therapy are important for successful treatment.
Successful management of an advanced interstitial ectopic pregnancy in a resource-limited setting: a case report
Authors: Tankeng Clovis Achassi , Ekei Quinta Mua , Ngunyi Yannick Lechedem , Yeika Eugene Vernyuy , Ajabmoh Elvis Nkengasong , Mokom Alfred Awa
Published: March 2024

Background

Interstitial ectopic pregnancy is an ectopic gestation developing in the uterine part of the fallopian tube. The condition is rare and presents challenges for clinical as well as radiological diagnosis. This case report presents a rare case of interstitial ectopic pregnancy diagnosed intraoperatively.

Case presentation

A 36-year-old Black woman, referred from a peripheral health facility, presented at the emergency department with severe abdominal pains, vaginal spotting, nausea, and vomiting, with a 2-month history of irregular menstrual flow. Clinical and laboratory findings were suggestive of an acute abdomen likely due to a ruptured ectopic pregnancy (ultrasound was not available). An emergency exploratory laparotomy was done, which revealed a right adnexal ruptured interstitial pregnancy of a lifeless female fetus weighing 500 g (estimated mean gestational age of 22–23 weeks). The left fallopian tube looked normal. The site of rupture was repaired, followed by cleaning and closure of the abdomen. The post-operative period was uneventful, and the patient was discharged on postoperative day 7.

Conclusion

Interstitial pregnancies are uncommon and rarely attain advanced gestational ages, as in this case, compared with other tubal ectopic pregnancies. However, women presenting with signs of hypovolemic shock and acute abdomen, with a positive pregnancy test, warrant a high index of suspicion.
Managing a difficult airway due to supraglottic masses: successful videolaryngoscopic intubation after induction of general anesthesia
Authors: Jeong Hye-won , Song Eun-Jin , Jang Eun-A , Kim Joungmin
Published: March 2024

Background

While awake, flexible bronchoscopic intubation has long been considered the gold standard for managing anticipated difficult airways, the videolaryngoscope has emerged as a viable alternative. In addition, the decision to perform awake intubation or to proceed with airway management after induction of general anesthesia should be grounded in a comprehensive assessment of risks and benefits.

Case presentation

A 41-year old female patient was scheduled for excision of bilateral, mobile, and pedunculated masses on both aryepiglottic folds, which covered almost the entire upper part of the glottis. We conducted a comprehensive evaluation of the patient’s signs and symptoms, which included neither stridor nor dyspnea in any position, along with the otolaryngologist’s opinion and the findings from the laryngeal fiberscopic examination. Given the potential challenges and risks associated with awake flexible bronchoscopic intubation for this patient, we decided to proceed with gentle tracheal intubation using a videolaryngoscope under general anesthesia. In case of failed mask ventilation and tracheal intubation, we had preplanned strategies, including awakening the patient or performing an emergent tracheostomy, along with preparations to support these strategies. Ensuring that mask ventilation was maintained with ease, the patient was sequentially administered intravenous propofol, remifentanil, and rocuronium. Under sufficient depth of anesthesia, intubation using a videolaryngoscope was successfully performed without any complications.

Conclusions

Videolaryngoscopic intubation after induction of general anesthesia can be a feasible alternative for managing difficult airways in patients with supraglottic masses. This approachshould be based on a comprehensive preoperative evaluation, adequate preparation, and preplanned strategies to address potential challenges, such as inadequate oxygenation and unsuccessful tracheal intubation.
Fostering positive attitudes toward food in individuals with restrained eating: the impact of flexible food-related inhibition
Authors: Berebbi Shir , Naftalovich Hadar , Weinbach Noam , Kalanthroff Eyal
Published: March 2024

Individuals exhibiting restrained eating behaviors demonstrate increased inhibitory control when exposed to food-related stimuli, indicating the presence of an automatic food-inhibition association. Existing literature proposes that this association contributes to the devaluation of food within this population. Efforts to disrupt this association by promoting the complete elimination of the inhibition of food responses have resulted in increased food consumption but have also led to heightened food-related anxiety in individuals with restrained eating behaviors. In the current investigation, we investigated whether a novel flexible food response/inhibition computerized task could yield favorable changes in attitudes toward food in individuals with restrained eating. We randomly assigned 78 females who engage in restrained eating to one of three training groups. In the flexible response/inhibition group, participants were instructed to equally inhibit or respond to food stimuli. In the response group, participants consistently responded to food stimuli, while in the inhibition group, participants consistently inhibited their response to food cues. Implicit attitudes toward food were assessed both before and after the manipulation. To examine the stability of the effect of the training, participants also engaged in a seemingly unrelated bogus taste test. Our results revealed that only the flexible response/inhibition group demonstrated a significant improvement in positive attitudes toward high-calorie foods after eating, while there were no observable changes in negative attitudes among the other two groups. These findings suggest that promoting a balance between the responding and inhibiting responses to food stimuli can increase positive attitudes toward food amongst individuals with restrained eating.
Tipping the balance in autoimmunity: are regulatory t cells the cause, the cure, or both?
Authors: Hardtke-Wolenski Matthias , Landwehr-Kenzel Sybille
Published: March 2024

Regulatory T cells (Tregs) are a specialized subgroup of T-cell lymphocytes that is crucial for maintaining immune homeostasis and preventing excessive immune responses. Depending on their differentiation route, Tregs can be subdivided into thymically derived Tregs (tTregs) and peripherally induced Tregs (pTregs), which originate from conventional T cells after extrathymic differentiation at peripheral sites. Although the regulatory attributes of tTregs and pTregs partially overlap, their modes of action, protein expression profiles, and functional stability exhibit specific characteristics unique to each subset. Over the last few years, our knowledge of Treg differentiation, maturation, plasticity, and correlations between their phenotypes and functions has increased. Genetic and functional studies in patients with numeric and functional Treg deficiencies have contributed to our mechanistic understanding of immune dysregulation and autoimmune pathologies. This review provides an overview of our current knowledge of Treg biology, discusses monogenetic Treg pathologies and explores the role of Tregs in various other autoimmune disorders. Additionally, we discuss novel approaches that explore Tregs as targets or agents of innovative treatment options.
A case of indirect inguinal bladder hernia treated with laparoscopic transabdominal preperitoneal repair with high peritoneal incisional approach
Authors: Zotani Hitomi , Yamamoto Tetsu , Hyakudomi Ryoji , Takai Kiyoe , Taniura Takahito , Ishitobi Kazunari , Hirahara Noriyuki , Tajima Yoshitsugu , Hidaka Masaaki
Published: March 2024

Background

Inguinal herniation of the urinary bladder is uncommon and those descending into the scrotum are even rarer. Although open anterior repair has been used for inguinal bladder hernia, the efficacy of laparoscopic herniorrhaphy has been reported in recent years.

Case presentation

A 63-year-old man presented with an irreducible right groin and scrotal bulge associated with voiding difficulty. Abdominal ultrasonography showed a dislocation of the urinary bladder descending into the right scrotum. Abdominal CT imaging revealed that a part of the bladder and small intestine was herniating into the scrotum through the internal inguinal ring and running laterally to the inferior epigastric artery. Under the diagnosis of indirect inguinal bladder hernia, the patient underwent trans-abdominal preperitoneal hernia repair (TAPP). The bladder herniated into the scrotum through the internal inguinal ring was replaced to the original position. Then the myopectineal orifice was exposed and covered with polypropylene mesh, where a horizontal peritoneal incision 4 cm above the hernia orifice, i.e., the high peritoneal incision approach (HPIA), allowed an easy peeling of the peritoneum and hernia sac. The patient’s postoperative course was uneventful and the voiding difficulty resolved. The patient continued to do well without recurrence at 20 months after surgery.

Conclusion

Preoperative evaluation with abdominal ultrasonography and CT scan allowed a precise diagnosis of a groin hernia with voiding difficulty. TAPP with HPIA was useful in the treatment of inguinal bladder hernia because this technique facilitated a quick confirmation of the hernia contents, secure dissection of the whole protruded bladder, and adequate replacement of the bladder to the original position without any injury.
Transgender and non-binary patient simulations can foster cultural sensitivity and knowledge among internal medicine residents: a pilot study
Authors: Borowicz Charlie , Daniel Laura , Futcher Regina D. , Wilfong Donamarie N.
Published: March 2024

Transgender and nonbinary patients face unique healthcare challenges, such as harassment, discrimination, and/or prejudice, at higher rates than their cisgender counterparts. These experiences, or even the fear of these experiences, may push patients to delay or forego medical treatment, thus compounding any existing conditions. Such extraneous issues can be combatted through cultural sensitivity. The authors designed blended education consisting of an online module followed by a live simulation to educate and promote sensitivity. Internal medicine (IM) residents (n = 94) completed the module, which introduced them to transgender community terminology and medical disparities, and ways to incorporate affirming behaviors into their practice. Afterward, they engaged in a simulation with true transgender-simulated patients (SPs) — either trans-masculine, trans-feminine, or non-binary. Residents were expected to conduct a patient interview mirroring an intake appointment. Residents then engaged in a debriefing session with the lead investigator and the SP to reflect on the experience, receive feedback and constructive criticism, and ask questions. After the education, the residents’ knowledge significantly increased, t(66) = 3.69, p ≤ 0.00, d = 0.45, and their attitude toward members of the transgender community also increased significantly, t(62) = 7.57, p ≤ 0.00, d = 0.95. Furthermore, nearly all residents (99%) reported the training allowed them to practice relevant skills and was a worthy investment of their time. Nearly half (45%) of the residents who listed changes they will make to their practice pledged to ask patients for their preferred name and pronouns. Most comments were positive (75%), praising the education’s effectiveness, expressing gratitude, and reporting increased confidence. Results provided evidence that the education was effective in increasing IM residents’ knowledge and attitudes. Further research is needed to investigate the longitudinal effects of this education and to extend the education to a broader audience. The investigators plan to adapt and expand the research to other specialties such as gynecology and emergency medicine.
Anesthetic Sevoflurane Induces Enlargement of Dendritic Spine Heads in Mouse Neurons via Tau-Dependent Mechanisms
Authors: Yan Jia , Ton Hoai , Yan Jing , Dong Yuanlin , Xie Zhongcong , Jiang Hong
Published: March 2024

BACKGROUND:

Sevoflurane induces neuronal dysfunction and cognitive impairment. However, the underlying mechanism remains largely to be determined. Tau, cyclophilin D, and dendritic spine contribute to cognitive function. But whether changes in dendritic spines are involved in the effects of sevoflurane and the potential association with tau and cyclophilin D is not clear.

METHODS:

We harvested hippocampal neurons from wild-type mice, tau knockout mice, and cyclophilin D knockout mice. We treated these neurons with sevoflurane at day in vitro 7 and measured the diameter of dendritic spine head and the number of dendritic spines. Moreover, we determined the effects of sevoflurane on the expression of excitatory amino acid transporter 3 (EAAT3), extracellular glutamate levels, and miniature excitatory postsynaptic currents (mEPSCs). Finally, we used lithium, cyclosporine A, and overexpression of EAAT3 in the interaction studies.

RESULTS:

Sevoflurane-induced tau phosphgorylation increased the diameter of dendritic spine head and decreased the number of dendritic spines in neurons harvested from wild-type and cyclophilin D knockout mice, but not tau knockout mice. Sevoflurane decreased the expression of EAAT3, increased extracellular glutamate levels, and decreased the frequency of mEPSCs in the neurons. Overexpression of EAAT3 mitigated the effects of sevoflurane on dendritic spines. Lithium, but not cyclosporine A, attenuated the effects of sevoflurane on dendritic spines. Lithium also inhibited the effects of sevoflurane on EAAT3 expression and mEPSCs.

CONCLUSIONS:

These data suggest that sevoflurane induces a tau phosphorylation-dependent demtrimental effect on dendritic spine via decreasing EAAT3 expression and increasing extracellular glutamate levels, leading to neuronal dysfunction.