bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting neutrophil extracellular trap accumulation under flow in patients with immune-mediated thrombotic thrombocytopenic purpura
Authors: Yada Noritaka , Zhang Quan , Bignotti Antonia , Gralnek Sarah H. , Sosnovske Dennis , Hogan Keenan , Ye Zhan , Zheng Liang , Zheng X. Long
Published: March 2024

Neutrophil NETosis is a unique form of cell death, characterized by the release of decondensed chromatin and antimicrobial contents to the extracellular space, which is involved in inflammation and thrombosis. However, the role of NETosis in the pathogenesis of immune-mediated thrombotic thrombocytopenic purpura (iTTP) and how a targeted therapy affects the accumulation of neutrophil extracellular traps (NETs) under flow remain unknown. Flow cytometry demonstrated that the percentage of neutrophils undergoing NETosis in whole blood from patients with iTTP on admission was significantly increased, with a concurrent decrease in the capacity of inducible NETosis by shigatoxin. After therapy, the percentage of H3Cit+MPO+ neutrophils was significantly reduced, with an improvement in inducible NETosis in these patients. Additionally, little to no NET and thrombus formation was detected underflow in the whole blood from patients with iTTP when platelet counts were very low, but the NET and thrombus formation was dramatically increased following therapy when platelet counts rose to ≥50 × 109/L or were restored to normal with donor platelets. Similarly, there was no thrombus or NET accumulation under flow in the whole blood from vwf-/- mice, but NET accumulation was significantly higher in Adamts13-/- mice than in wild-type mice. Finally, recombinant ADAMTS13 or caplacizumab (or anfibatide) prevented NET and thrombus formation under flow in whole blood from patients with iTTP or from Adamts13-/- mice. These results indicate that neutrophil NETosis and NET formation depend on platelets and von Willebrand factor (VWF) in iTTP, and a targeted therapy such as recombinant ADAMTS13 or caplacizumab may prevent NET and thrombus formation under flow in iTTP.
Genomic profiling of mycosis fungoides identifies patients at high risk of disease progression
Authors: Fléchon Léa , Arib Inès , Dutta Ankit K. , Hasan Bou Issa Lama , Sklavenitis-Pistofidis Romanos , Tilmont Rémi , Stewart Chip , Dubois Romain , Poulain Stéphanie , Copin Marie-Christine , Javed Sahir , Nudel Morgane , Cavalieri Doriane , Escure Guillaume , Gower Nicolas , Chauvet Paul , Gazeau Nicolas , Saade Cynthia , Thiam Marietou Binta , Ouelkite-Oumouchal Aïcha , Gaggero Silvia , Cailliau Émeline , Faiz Sarah , Carpentier Olivier , Duployez Nicolas , Idziorek Thierry , Mortier Laurent , Figeac Martin , Preudhomme Claude , Quesnel Bruno , Mitra Suman , Morschhauser Franck , Getz Gad , Ghobrial Irene M. , Manier Salomon
Published: March 2024

Mycosis fungoides (MF) is the most prevalent primary cutaneous T-cell lymphoma, with an indolent or aggressive course and poor survival. The pathogenesis of MF remains unclear, and prognostic factors in the early stages are not well established. Here, we characterized the most recurrent genomic alterations using whole-exome sequencing of 67 samples from 48 patients from Lille University Hospital (France), including 18 sequential samples drawn across stages of the malignancy. Genomic data were analyzed on the Broad Institute’s Terra bioinformatics platform. We found that gain7q, gain10p15.1 (IL2RA and IL15RA), del10p11.22 (ZEB1), or mutations in JUNB and TET2 are associated with high-risk disease stages. Furthermore, gain7q, gain10p15.1 (IL2RA and IL15RA), del10p11.22 (ZEB1), and del6q16.3 (TNFAIP3) are coupled with shorter survival. Del6q16.3 (TNFAIP3) was a risk factor for progression in patients at low risk. By analyzing the clonal heterogeneity and the clonal evolution of the cohort, we defined different phylogenetic pathways of the disease with acquisition of JUNB, gain10p15.1 (IL2RA and IL15RA), or del12p13.1 (CDKN1B) at progression. These results establish the genomics and clonality of MF and identify potential patients at risk of progression, independent of their clinical stage.
Sex and fetal genome influence gene expression in pig endometrium at the end of gestation
Authors: Bonnet Agnes , Bluy Lisa , Gress Laure , Canario Laurianne , Ravon Laure , Sécula Aurelie , Billon Yvon , Liaubet Laurence
Published: March 2024

Background

A fine balance of feto-maternal resource allocation is required to support pregnancy, which depends on interactions between maternal and fetal genetic potential, maternal nutrition and environment, endometrial and placental functions. In particular, some imprinted genes have a role in regulating maternal-fetal nutrient exchange, but few have been documented in the endometrium. The aim of this study is to describe the expression of 42 genes, with parental expression, in the endometrium comparing two extreme breeds: Large White (LW); Meishan (MS) with contrasting neonatal mortality and maturity at two days of gestation (D90-D110). We investigated their potential contribution to fetal maturation exploring genes-fetal phenotypes relationships. Last, we hypothesized that the fetal genome and sex influence their endometrial expression. For this purpose, pure and reciprocally crossbred fetuses were produced using LW and MS breeds. Thus, in the same uterus, endometrial samples were associated with its purebred or crossbred fetuses.

Results

Among the 22 differentially expressed genes (DEGs), 14 DEGs were differentially regulated between the two days of gestation. More gestational changes were described in LW (11 DEGs) than in MS (2 DEGs). Nine DEGs were differentially regulated between the two extreme breeds, highlighting differences in the regulation of endometrial angiogenesis, nutrient transport and energy metabolism. We identified DEGs that showed high correlations with indicators of fetal maturation, such as ponderal index at D90 and fetal blood fructose level and placental weight at D110.

We pointed out for the first time the influence of fetal sex and genome on endometrial expression at D90, highlightingAMPD3,CITED1andH19genes. We demonstrated that fetal sex affects the expression of five imprinted genes in LW endometrium. Fetal genome influenced the expression of four genes in LW endometrium but not in MS endometrium. Interestingly, both fetal sex and fetal genome interact to influence endometrial gene expression.

Conclusions

These data provide evidence for some sexual dimorphism in the pregnant endometrium and for the contribution of the fetal genome to feto-maternal interactions at the end of gestation. They suggest that the paternal genome may contribute significantly to piglet survival, especially in crossbreeding production systems.
APOE ε4 carriage associates with improved myocardial performance from adolescence to older age
Authors: Topriceanu Constantin-Cristian , Shah Mit , Webber Matthew , Chan Fiona , Shiwani Hunain , Richards Marcus , Schott Jonathan , Chaturvedi Nishi , Moon James C. , Hughes Alun D. , Hingorani Aroon D. , O’Regan Declan P. , Captur Gabriella
Published: March 2024

Background

Although APOE ε4 allele carriage confers a risk for coronary artery disease, its persistence in humans might be explained by certain survival advantages (antagonistic pleiotropy).

Methods

Combining data from ~ 37,000 persons from three older age British cohorts (1946 National Survey of Health and Development [NSHD], Southall and Brent Revised [SABRE], and UK Biobank) and one younger age cohort (Avon Longitudinal Study of Parents and Children [ALSPAC]), we explored whether APOE ε4 carriage associates with beneficial or unfavorable left ventricular (LV) structural and functional metrics by echocardiography and cardiovascular magnetic resonance (CMR).

Results

Compared to the non-APOE ε4 group, APOE ε4 carriers had similar cardiac phenotypes in terms of LV ejection fraction, E/e’, posterior wall and interventricular septal thickness, and LV mass. However, they had improved myocardial performance resulting in greater LV stroke volume generation per 1 mL of myocardium (higher myocardial contraction fraction). In NSHD (n = 1467) and SABRE (n = 1187), ε4 carriers had a 4% higher MCF (95% CI 1–7%, p = 0.016) using echocardiography. Using CMR data, in UK Biobank (n = 32,972), ε4 carriers had a 1% higher MCF 95% (CI 0–1%, p = 0.020) with a dose-response relationship based on the number of ε4 alleles. In addition, UK Biobank ε4 carriers also had more favorable radial and longitudinal strain rates compared to non APOE ε4 carriers. In ALSPAC (n = 1397), APOE ε4 carriers aged < 24 years had a 2% higher MCF (95% CI 0–5%, p = 0.059).

Conclusions

By triangulating results in four independent cohorts, across imaging modalities (echocardiography and CMR), and in ~ 37,000 individuals, our results point towards an association between ε4 carriage and improved cardiac performance in terms of LV MCF. This potentially favorable cardiac phenotype adds to the growing number of reported survival advantages attributed to the pleiotropic effects APOE ε4 carriage that might collectively explain its persistence in human populations.
Empowering child health: Harnessing machine learning to predict acute respiratory infections in Ethiopian under-fives using demographic and health survey insights
Authors: Kalayou Mulugeta Hayelom , Kassaw Abdul-Aziz Kebede , Shiferaw Kirubel Biruk
Published: March 2024

Background

A dearth of studies showed that infectious diseases cause the majority of deaths among under-five children. Worldwide, Acute Respiratory Infection (ARI) continues to be the second most frequent cause of illness and mortality among children under the age of five. The paramount disease burden in developing nations, including Ethiopia, is still ARI.

Objective

This study aims to determine the magnitude and predictors of ARI among under-five children in Ethiopia using used state of the art machine learning algorithms.

Methods

Data for this study were derived from the 2016 Ethiopian Demographic and Health Survey. To predict the determinants of acute respiratory infections, we performed several experiments on ten machine learning algorithms (random forests, decision trees, support vector machines, Naïve Bayes, and K-nearest neighbors, Lasso regression, GBoost, XGboost), including one classic logistic regression model and an ensemble of the best performing models. The prediction ability of each machine-learning model was assessed using receiver operating characteristic curves, precision-recall curves, and classification metrics.

Results

The total ARI prevalence rate among 9501 under-five children in Ethiopia was 7.2%, according to the findings of the study. The overall performance of the ensemble model of SVM, GBoost, and XGBoost showed an improved performance in classifying ARI cases with an accuracy of 86%, a sensitivity of 84.6%, and an AUC-ROC of 0.87. The highest performing predictive model (the ensemble model) showed that the child’s age, history of diarrhea, wealth index, type of toilet, mother’s educational level, number of living children, mother’s occupation, and type of fuel they used were an important predicting factor for acute respiratory infection among under-five children.

Conclusion

The intricate web of factors contributing to ARI among under-five children was identified using an advanced machine learning algorithm. The child’s age, history of diarrhea, wealth index, and type of toilet were among the top factors identified using the ensemble model that registered a performance of 86% accuracy. This study stands as a testament to the potential of advanced data-driven methodologies in unraveling the complexities of ARI in low-income settings.
Long-term multicenter comparison shows equivalent efficacy of monoclonal antibodies in severe asthma therapy
Authors: Kayser Moritz Z. , Suhling Hendrik , Fuge Jan , Hinze Christopher A. , Drick Nora , Kneidinger Nikolaus , Behr Jürgen , Taube Christian , Welte Tobias , Haasler Ina , Milger Katrin
Published: March 2024

Background

Monoclonal antibodies (biologics) drastically changed severe asthma therapy. Mepolizumab (anti-interleukin (IL) 5), benralizumab (anti-IL5 receptor alpha), and dupilumab (anti-IL4/13) are the most used biologics in this context. While all biologics are efficient individually, the choice of biologic is complicated by insufficient data on their comparative long-term treatment efficacy. Here, we compare the real-life efficacy of these biologics in asthma therapy over 12 months.

Methods

280 severe asthma patients treated with mepolizumab (129/280, 46%), benralizumab (83/280, 30%) or dupilumab (68/280, 24%) for one year were analyzed retrospectively. Data were collected at baseline and after 6 and 12 months of therapy. Endpoints were changes pulmonary function (PF), exacerbation rate, oral corticosteroid (OCS) use and dose, asthma control test (ACT) score and fractional exhaled nitric oxide (FeNO) levels as well as responder status measured by the recently published “Biologic Asthma Response Score” (BARS).

Results

All biologics led to significant improvements in PF, ACT and OCS dose. Only Mepolizumab and Benralizumab significantly decreased the exacerbation rate, while only Mepolizumab and Dupilumab significantly decreased FeNO. Responder rates measured by BARS were high across all groups: roughly half of all patients achieved full response and most of the remainder achieved at least partial responder status. Overall, outcomes were similar between groups after both 6 and 12 months.

Conclusions

All biologics showed great efficacy in individual parameters and high responder rates measured by BARS without a clinically relevant advantage for any antibody. Response was usually achieved after 6 months and retained at 12 months, emphasizing the utility of early response assessment.
Aesthetic impact of resin infiltration and its mechanical effect on ceramic bonding for white spot lesions
Authors: Shu Jiaen , Huang Yijia , Ma Xueying , Duan Zhonghua , Wu Pei , Chu Sijing , Wu Yuqiong , Wang Yuhua
Published: March 2024

Background

Treating white spot lesions (WSLs) with resin infiltration alone may not be sufficient, raising questions about its compatibility with other treatments amid controversial or incomplete data. Therefore, this study aimed to assess the aesthetic feasibility of resin infiltration combined with bleaching, as well as its potential mechanical effect on ceramic bonding to WSLs.

Methods

One hundred and fifty flat enamel surfaces of bovine incisors were prepared. Ninety specimens were deminerailized and randomly assigned to three groups(n = 30): post-bleaching resin infiltration (Bl-R), pre-bleaching resin infiltration (R-Bl), and only resin infiltration (R). Color, surface roughness and microhardness were assessed in immediate, thermocycling and pigmentation tests. The remaining sixty samples were randomly assigned to three groups (n = 20): control (Ctrl), bonding (Bo), pre-bonding resin infiltration (R-Bo). Shear bonding strength, failure mode, micro-leakage depth and interface morphology were evaluated after ceramic bonding. The Tukey test and analysis of variance (ANOVA) were used for statistical analysis.

Results

For the effect of resin infiltration and bleaching on WSLs, the R-Bl group showed the worst chromic masking ability, with the highest |ΔL|, |Δa|, |Δb|, and ΔE values after treatment. Compared with those in the Bl-R group, the R-Bl and R groups showed significant time-dependent staining, which is possibly attributed to their surface roughness. For the effect of resin infiltration on the adhesive properties of WSLs, resin infiltration reduced the staining penetration depth of WSLs from 2393.54 ± 1118.86 μm to 188.46 ± 89.96 μm (P < 0.05) while reducing WSLs porosity in SEM observation.

Conclusions

Post-bleaching resin infiltration proved to be advantageous in the aesthetic treatment of WSLs. Resin infiltration did not compromise bonding strength but it did reduce microleakage and enhance marginal sealing. Overall, resin infiltration can effectively enhance the chromatic results of treated WSLs and prevent long-term bonding failure between ceramics and enamel. Based on these findings, the use of post-bleaching resin infiltration is recommended, and resin infiltration before ceramic bonding is deemed viable in clinical practice.
Noninvasive monitoring technologies to identify discomfort and distressing symptoms in persons with limited communication at the end of life: a scoping review
Authors: Xu Jingyuan , Smaling Hanneke J. A. , Schoones Jan W. , Achterberg Wilco P. , van der Steen Jenny T.
Published: March 2024

Background

Discomfort and distressing symptoms are common at the end of life, while people in this stage are often no longer able to express themselves. Technologies may aid clinicians in detecting and treating these symptoms to improve end-of-life care. This review provides an overview of noninvasive monitoring technologies that may be applied to persons with limited communication at the end of life to identify discomfort.

Methods

A systematic search was performed in nine databases, and experts were consulted. Manuscripts were included if they were written in English, Dutch, German, French, Japanese or Chinese, if the monitoring technology measured discomfort or distressing symptoms, was noninvasive, could be continuously administered for 4 hours and was potentially applicable for bed-ridden people. The screening was performed by two researchers independently. Information about the technology, its clinimetrics (validity, reliability, sensitivity, specificity, responsiveness), acceptability, and feasibility were extracted.

Results

Of the 3,414 identified manuscripts, 229 met the eligibility criteria. A variety of monitoring technologies were identified, including actigraphy, brain activity monitoring, electrocardiography, electrodermal activity monitoring, surface electromyography, incontinence sensors, multimodal systems, and noncontact monitoring systems. The main indicators of discomfort monitored by these technologies were sleep, level of consciousness, risk of pressure ulcers, urinary incontinence, agitation, and pain. For the end-of-life phase, brain activity monitors could be helpful and acceptable to monitor the level of consciousness during palliative sedation. However, no manuscripts have reported on the clinimetrics, feasibility, and acceptability of the other technologies for the end-of-life phase.

Conclusions

Noninvasive monitoring technologies are available to measure common symptoms at the end of life. Future research should evaluate the quality of evidence provided by existing studies and investigate the feasibility, acceptability, and usefulness of these technologies in the end-of-life setting. Guidelines for studies on healthcare technologies should be better implemented and further developed.
Knowledge of cytology results affects the performance of colposcopy: a crossover study
Authors: Lalande Eva , Clarke Holly , Undurraga Manuela , Nguyen Vu Quoc Huy , Jaksic Cyril , Goffin Frederic , Arbyn Marc , Jeronimo Jose , Tille Jean-Christophe , Saiji Essia , Vassilakos Pierre , Petignat Patrick
Published: March 2024

Objective

To determine whether knowledge of cytology affects the colposcopist’s diagnostic accuracy in the identification of cervical intraepithelial neoplasia grade 2 and worse (≥ CIN2).

Method

In this cross-over study, healthcare professionals interpreted colposcopy images from 80 patient cases with known histological diagnoses. For each case, 2 images taken with a colposcope were provided (native and after acetic acid application). Inclusion criteria consisted of women with a transformation zone type 1 or 2, who had both a cytological and histological diagnosis. Cases were distributed across two online surveys, one including and one omitting the cytology. A wash-out period of six weeks between surveys was implemented. Colposcopists were asked to give their diagnosis for each case as < CIN2 or ≥ CIN2 on both assessments. Statistical analysis was conducted to compare the two interpretations.

Results

Knowledge of cytology significantly improved the sensitivity when interpreting colposcopic images, from 51.1% [95%CI: 39.3 to 62.8] to 63.7% [95%CI: 52.1 to 73.9] and improved the specificity from 63.5% [95%CI: 52.3 to 73.5] to 76.6% [95%CI: 67.2 to 84.0]. Sensitivity was higher by 38.6% when a high-grade cytology (ASC-H, HSIL, AGC) was communicated compared to a low-grade cytology (inflammation, ASC-US, LSIL). Specificity was higher by 31% when a low-grade cytology was communicated compared to a high-grade.

Conclusions

Our data suggests that knowledge of cytology increases sensitivity and specificity for diagnosis of ≥ CIN2 lesions at colposcopy. Association between cytology and histology may have contributed to the findings.
Multimodal deep learning-based diagnostic model for BPPV
Authors: Lu Hang , Mao Yuxing , Li Jinsen , Zhu Lin
Published: March 2024

Background

Benign paroxysmal positional vertigo (BPPV) is a prevalent form of vertigo that necessitates a skilled physician to diagnose by observing the nystagmus and vertigo resulting from specific changes in the patient’s position. In this study, we aim to explore the integration of eye movement video and position information for BPPV diagnosis and apply artificial intelligence (AI) methods to improve the accuracy of BPPV diagnosis.

Methods

We collected eye movement video and diagnostic data from 518 patients with BPPV who visited the hospital for examination from January to March 2021 and developed a BPPV dataset. Based on the characteristics of the dataset, we propose a multimodal deep learning diagnostic model, which combines a video understanding model, self-encoder, and cross-attention mechanism structure.

Result

Our validation test on the test set showed that the average accuracy of the model reached 81.7%, demonstrating the effectiveness of the proposed multimodal deep learning method for BPPV diagnosis. Furthermore, our study highlights the significance of combining head position information and eye movement information in BPPV diagnosis. We also found that postural and eye movement information plays a critical role in the diagnosis of BPPV, as demonstrated by exploring the necessity of postural information for the diagnostic model and the contribution of cross-attention mechanisms to the fusion of postural and oculomotor information. Our results underscore the potential of AI-based methods for improving the accuracy of BPPV diagnosis and the importance of considering both postural and oculomotor information in BPPV diagnosis.
Transforming health care systems towards high-performance organizations: qualitative study based on learning from COVID-19 pandemic in the Basque Country (Spain)
Authors: Fullaondo Ane , Erreguerena Irati , Keenoy Esteban de Manuel
Published: March 2024

Background

The COVID-19 pandemic is one of the worst health catastrophes of the last century, which caused severe economic, political, and social consequences worldwide. Despite these devastating consequences, lessons learned provide a great opportunity that can drive the reform of health systems to become high-performing, effective, equitable, accessible, and sustainable organisations. This work identifies areas in which changes must be encouraged that will enable health systems to deal effectively with current and future challenges, beyond COVID-19.

Methods

A realist design was chosen, based on qualitative data collection techniques, content analysis and triangulation to identify key domains of organizational interventions behind the changes implemented to react to the COVID-19 pandemic in the Basque Country. Twenty key informants were used as an expert source of information. Thematic analysis was done using the Framework Method.

Results

The analysis of the interviews resulted in the identification of 116 codes, which were reviewed and agreed upon by the researchers. Following the process of methodological analysis, these codes were grouped into domains: seven themes and 23 sub-themes. Specifically, the themes are: responsiveness, telehealth, integration, knowledge management, professional roles, digitisation, and organisational communication. The detailed description of each theme and subtheme is presented.

Conclusions

The findings of this work pretend to guide the transformation of health systems into organisations that can improve the health of their populations and provide high quality care. Such a multidimensional and comprehensive reform encompasses both strategic and operational actions in diverse areas and requires a broad and sustained political, technical, and financial commitment.
LDLR c.415G > A causes familial hypercholesterolemia by weakening LDLR binding to LDL
Authors: Wang Kaihan , Hu Tingting , Tai Mengmeng , Shen Yan , Chai Haocheng , Lin Shaoyi , Chen Xiaomin
Published: March 2024

Background

Familial hypercholesterolemia (FH) is a prevalent hereditary disease that can cause aberrant cholesterol metabolism. In this study, we confirmed that c.415G > A in low-density lipoprotein receptor (LDLR), an FH-related gene, is a pathogenic variant in FH by in silico analysis and functional experiments.

Methods

The proband and his family were evaluated using the diagnostic criteria of the Dutch Lipid Clinic Network. Whole-exome and Sanger sequencing were used to explore and validate FH-related variants. In silico analyses were used to evaluate the pathogenicity of the candidate variant and its impact on protein stability. Molecular and biochemical methods were performed to examine the effects of the LDLR c.415G > A variant in vitro.

Results

Four of six participants had a diagnosis of FH. It was estimated that the LDLR c.415G > A variant in this family was likely pathogenic. Western blotting and qPCR suggested that LDLR c.415G > A does not affect protein expression. Functional studies showed that this variant may lead to dyslipidemia by impairing the binding and absorption of LDLR to low-density lipoprotein ( LDL).

Conclusion

LDLR c.415G > A is a pathogenic variant in FH; it causes a significant reduction in LDLR’s capacity to bind LDL, resulting in impaired LDL uptake. These findings expand the spectrum of variants associated with FH.
Acetyl-CoA synthetase 2 induces pyroptosis and inflammation of renal epithelial tubular cells in sepsis-induced acute kidney injury by upregulating the KLF5/NF-κB pathway
Authors: Lu Jian , Hou Ya , Liu Si-Xiu , Jin Bo , Liu Jing , Li Nan , Zhu Yan , Zhang Qing-Yan , Wan Cheng , Feng Yuan , Xie Jun , Jiang Chun-Ming
Published: March 2024

Background

Pyroptosis of the renal tubular epithelial cells (RTECs) and interstitial inflammation are central pathological characteristics of acute kidney injury (AKI). Pyroptosis acts as a pro-inflammatory form of programmed cell death and is mainly dependent on activation of the NLRP3 inflammasome. Previous studies revealed that acetyl-CoA synthetase 2 (ACSS2) promotes inflammation during metabolic stress suggesting that ACSS2 might regulate pyroptosis and inflammatory responses of RTECs in AKI.

Methods and results

The expression of ACSS2 was found to be significantly increased in the renal epithelial cells of mice with lipopolysaccharide (LPS)-induced AKI. Pharmacological and genetic strategies demonstrated that ACSS2 regulated NLRP3-mediated caspase-1 activation and pyroptosis through the stimulation of the KLF5/NF-κB pathway in RTECs. The deletion of ACSS2 attenuated renal tubular pathological injury and inflammatory cell infiltration in an LPS-induced mouse model, and ACSS2-deficient mice displayed impaired NLRP3 activation-mediated pyroptosis and decreased IL-1β production in response to the LPS challenge. In HK-2 cells, ACSS2 deficiency suppressed NLRP3-mediated caspase-1 activation and pyroptosis through the downregulation of the KLF5/NF-κB pathway. The KLF5 inhibitor ML264 suppressed NF-κB activity and NLRP3-mediated caspase-1 activation, thus protecting HK-2 cells from LPS-induced pyroptosis.

Conclusion

Our results suggested that ACSS2 regulates activation of the NLRP3 inflammasome and pyroptosis by inducing the KLF5/NF-κB pathway in RTECs. These results identified ACSS2 as a potential therapeutic target in AKI.

Graphical Abstract

We found that the expression of ACSS2 was significantly increased in RTECs in septic AKI. ACSS2-deficient mice displayed resistance to renal damage in this model. ACSS2 regulated NLRP3-mediated caspase-1 activation and pyroptosis through the KLF5/NF-κB pathway in RTECs. Pharmacological inhibition of KLF5 suppressed NLRP3 activation and caspase-1 cleavage by downregulating of NF-κB. Our results suggest that ACSS2 is a pro-pathogenic mediator of cell pyroptosis of RTECs and renal inflammation in sepsis-induced AKI.
Epidemiology, clinical features and outcomes of hospitalized patients with COVID-19 by vaccination status: a multicenter historical cohort study
Authors: Alshanqeeti Shatha , Szpunar Susan , Anne Premchand , Saravolatz Louis , Bhargava Ashish
Published: March 2024

Introduction

COVID-19 disease resulted in over six million deaths worldwide. Although vaccines against SARS-CoV-2 demonstrated efficacy, breakthrough infections became increasingly common. There is still a lack of data regarding the severity and outcomes of COVID-19 among vaccinated compared to unvaccinated individuals.

Methods

This was a historical cohort study of adult COVID-19 patients hospitalized in five Ascension hospitals in southeast Michigan. Electronic medical records were reviewed. Vaccine information was collected from the Michigan Care Improvement Registry. Data were analyzed using Student’s t-test, analysis of variance, the chi-squared test, the Mann-Whitney and Kruskal-Wallis tests, and multivariable logistic regression.

Results

Of 341 patients, the mean age was 57.9 ± 18.3 years, 54.8% (187/341) were female, and 48.7% (166/341) were black/African American. Most patients were unvaccinated, 65.7%, 8.5%, and 25.8% receiving one dose or at least two doses, respectively. Unvaccinated patients were younger than fully vaccinated (p = 0.001) and were more likely to be black/African American (p = 0.002). Fully vaccinated patients were 5.3 times less likely to have severe/critical disease (WHO classification) than unvaccinated patients (p < 0.001) after controlling for age, BMI, race, home steroid use, and serum albumin levels on admission. The case fatality rate in fully vaccinated patients was 3.4% compared to 17.9% in unvaccinated patients (p = 0.003). Unvaccinated patients also had higher rates of complications.

Conclusions

Patients who were unvaccinated or partially vaccinated had more in-hospital complications, severe disease, and death as compared to fully vaccinated patients. Factors associated with severe COVID-19 disease included advanced age, obesity, low serum albumin, and home steroid use.
The development of working alliance in early stages of care from the perspective of patients attending a chiropractic teaching clinic
Authors: Ivanova Dima , Newell Dave , Field Jonathan , Bishop Felicity L.
Published: March 2024

Background

The clinician-patient relationship has consistently been found to predict treatment success in both physical and mental health settings. This relationship has been operationalised in the literature as “Working Alliance,” which consists of three key components: patient-clinician agreement on the goals of care, agreement on the tasks required to achieve those goals, and the establishment of a strong bond. While research has demonstrated the impact of working alliance in physical health settings, it often measures working alliance early in patients’ care journeys. However, no primary research has investigated how early working alliance develops between patients and chiropractors. Evidence suggests that musculoskeletal practitioners may require further training to feel confident in establishing working alliance. Therefore, this study aims to explore the development of working alliance in the early stages of chiropractic care from the patients’ perspective to inform evidence-based practice.

Methods

Participants for this qualitative study were recruited from a teaching clinic at a specialised healthcare professions training university in the United Kingdom between September 2022 and April 2023. A total of 25 adult patients completed semi-structured interviews during the early stages of their care. The interview transcripts were analysed using Reflexive Thematic Analysis, from a critical realist stance.

Results

The findings highlight that an early working alliance entails the gradual development of patients’ confidence in their decision to seek help from trainee chiropractors to alleviate their symptoms. The four themes describe the impact of the clinical context on patients’ expectations, the trainee chiropractors’ qualities that participants considered important for early working alliance, the role of explanations, and the interplay between pain and early working alliance.

Conclusions

Establishing an early trainee chiropractor-patient working alliance involves a process of building patients’ confidence in the trainee chiropractors’ expertise, identifying the correct goals of care, and recognising the value of the proposed treatment plan. Factors shaping this process include the context of the care journey, patients’ perceptions of trainee chiropractors’ qualities, their bodily sensations, their expectations, their past experiences, and their satisfaction with trainee chiropractors’ explanations.
Valvar bypass surgery to ameliorate persistent lower limb edema caused by post-thrombotic syndrome: a case report and literature review
Authors: Wang Yanyang , Zhao Liang , Zhang Jie , Du Yali , Chen Jianfeng , Wu Yingfeng
Published: March 2024

Obstruction and/or reflux compromise during venous emptying can facilitate different pathophysiologies in chronic venous insufficiency (CVI). We present a patient with persistent lower limb CVI edema caused by post-thrombotic syndrome (PTS), who responded well to femoral vein valve therapy via axillary vein bypass after unsuccessful valvuloplasty, and led a normal life. During a 12 month observation period, bridging vessels completely restored original anatomical structures. In a literature study, no similar surgeries were reported, but we show that this operation may be feasible in selected patients.
Humanistic burden of pediatric type 1 diabetes on children and informal caregivers: systematic literature reviews
Authors: Allen Veleka , Mahieu Aymeric , Kasireddy Ellen , Shouman Walid , Pourrahmat Mir-Masoud , Collet Jean-Paul , Cherkas Andriy
Published: March 2024

Background

Diagnosis of children with type 1 diabetes (T1D) imposes an unprecedented burden on children and their caregivers.

Objective

To assess the burden of T1D on children and their informal caregivers, both after a recent diagnosis or after a longer duration of disease.

Methods

A series of systematic literature reviews were performed to explore the burden of T1D on children with the disease and their primary informal caregivers, based on the time of diagnosis. After the extraction of the qualitative and quantitative data from the included studies, two literature-based conceptual frameworks were developed: on the burden of pediatric T1D on children, and on informal caregivers. A third conceptual framework on the shared burden of pediatric T1D on both children and informal caregivers as part of the same family unit was also developed.

Results

The review of literature has identified a series of factors that affect the quality of life of children with T1D and their informal caregivers, with a direct impact on physical, emotional, and social outcomes. Generally, female patients and older adolescents experience more worry and stress that affects their quality of life. Other categories of factors affecting the child’s and caregiver’s burden include social, emotional, and physical factors, treatment-related and disease-related factors, as well as their coping abilities. Anxiety, depression, stress, and worry were commonly found among children and caregivers, starting with the diagnosis of T1D and continuing over time in relation to new challenges pertaining to aging or the disease duration.

Conclusion

T1D causes a significant burden to affected children and their caregivers, both independently and through transactional interaction within the family unit. Disease burden can be reduced by strengthening individuals for the benefit of the whole family.
Insurance barriers and inequalities in health care access: evidence from dual practice
Authors: Goetjes Eva , Blankart Katharina E.
Published: March 2024

Background

We investigate access disparities in pharmaceutical care among German patients with type 2 diabetes, focusing on differences between public and private health insurance schemes. The primary objectives include investigating whether patients with private health insurance experience enhanced access to antidiabetic care and analyzing whether the treatment received by public and private patients is influenced by the practice composition, particularly the proportion of private patients.

Methods

We estimate fixed effect regression models, to isolate the effect of insurance schemes on treatment choices. We utilize data from a prescriber panel comprising 681 physicians collectively serving 68,362 patients undergoing antidiabetic treatments.

Results

The analysis reveals a significant effect of the patient's insurance status on antidiabetic care access. Patients covered by private insurance show a 10-percentage-point higher likelihood of receiving less complex treatments compared to those with public insurance. Furthermore, the composition of physicians' practices plays a crucial role in determining the likelihood of patients receiving less complex treatments. Notably, the most pronounced disparities in access are observed in practices mirroring the regional average composition.

Conclusions

Our findings underscore strategic physician navigation across diverse health insurance schemes in ambulatory care settings, impacting patient access to innovative treatments.
AIoT-driven multi-source sensor emission monitoring and forecasting using multi-source sensor integration with reduced noise series decomposition
Authors: Bhatti Mughair Aslam , Song Zhiyao , Bhatti Uzair Aslam , M. S Syam
Published: March 2024

The integration of multi-source sensors based AIoT (Artificial Intelligence of Things) technologies into air quality measurement and forecasting is becoming increasingly critical in the fields of sustainable and smart environmental design, urban development, and pollution control. This study focuses on enhancing the prediction of emission, with a special emphasis on pollutants, utilizing advanced deep learning (DL) techniques. Recurrent neural networks (RNNs) and long short-term memory (LSTM) neural networks have shown promise in predicting air quality trends in time series data. However, challenges persist due to the unpredictability of air quality data and the scarcity of long-term historical data for training. To address these challenges, this study introduces the AIoT-enhanced EEMD-CEEMDAN-GCN model. This innovative approach involves decomposing the input signal using EEMD (Ensemble Empirical Mode Decomposition) and CEEMDAN (Complete Ensemble Empirical Mode Decomposition with Adaptive Noise) to extract intrinsic mode functions. These functions are then processed through a GCN (Graph Convolutional Network) model, enabling precise prediction of air quality trends. The model’s effectiveness is validated using air pollution datasets from four provinces in China, demonstrating its superiority over various deep learning models (GCN, EMD-GCN) and series decomposition models (EEMD-GCN, CEEMDAN-GCN). It achieves higher accuracy and better data fitting, outperforming other models in key metrics such as MAE (Mean Absolute Error), MSE (Mean Squared Error), MAPE (Mean Absolute Percentage Error), and R2 (Coefficient of Determination). The implementation of this AIoT-enhanced model in air pollution prediction allows decision-makers to more accurately anticipate changes in air quality, particularly concerning carbon emissions. This facilitates more effective planning of mitigation measures, improvement of public health, and optimization of resource allocation. Moreover, the model adeptly addresses the complexities of air quality data, contributing significantly to enhanced monitoring and management strategies in the context of sustainable urban development and environmental conservation.
Serine synthesis and catabolism in starved lung cancer and primary bronchial epithelial cells
Authors: Haitzmann Theresa , Schindlmaier Katharina , Frech Tobias , Mondal Ayusi , Bubalo Visnja , Konrad Barbara , Bluemel Gabriele , Stiegler Philipp , Lackner Stefanie , Hrzenjak Andelko , Eichmann Thomas , Köfeler Harald C. , Leithner Katharina
Published: March 2024

Serine and glycine give rise to important building blocks in proliferating cells. Both amino acids are either synthesized de novo or taken up from the extracellular space. In lung cancer, serine synthesis gene expression is variable, yet, expression of the initial enzyme, phosphoglycerate dehydrogenase (PHGDH), was found to be associated with poor prognosis. While the contribution of de novo synthesis to serine pools has been shown to be enhanced by serine starvation, the impact of glucose deprivation, a commonly found condition in solid cancers is poorly understood. Here, we utilized a stable isotopic tracing approach to assess serine and glycine de novo synthesis and uptake in different lung cancer cell lines and normal bronchial epithelial cells in variable serine, glycine, and glucose conditions. Under low glucose supplementation (0.2 mM, 3–5% of normal plasma levels), serine de novo synthesis was maintained or even activated. As previously reported, also gluconeogenesis supplied carbons from glutamine to serine and glycine under these conditions. Unexpectedly, low glucose treatment consistently enhanced serine to glycine conversion, along with an up-regulation of the mitochondrial one-carbon metabolism enzymes, serine hydroxymethyltransferase (SHMT2) and methylenetetrahydrofolate dehydrogenase (MTHFD2). The relative contribution of de novo synthesis greatly increased in low serine/glycine conditions. In bronchial epithelial cells, adaptations occurred in a similar fashion as in cancer cells, but serine synthesis and serine to glycine conversion, as assessed by label enrichments and gene expression levels, were generally lower than in (PHGDH positive) cancer cells. In summary, we found a variable contribution of glucose or non-glucose carbon sources to serine and glycine and a high adaptability of the downstream one-carbon metabolism pathway to variable glucose supply.
Moral disengagement and empathy in cyberbullying: how they are related in reflection activities about a serious game
Authors: Mateus Francisco Sofia , Costa Ferreira Paula , Veiga Simão Ana Margarida , Salgado Pereira Nádia
Published: March 2024

Cyberbullying is a complex phenomenon with multiple factors involved, both contextual and individual factors, such as moral disengagement and empathy. This study investigated how moral disengagement and empathy could be related, longitudinally in cyberbullying events. Specifically, two gamified tasks (one for empathy and other for moral disengagement) were analyzed. These tasks were developed attending to the specificities of the cyberbullying scenarios presented in a serious game. To accomplish this goal, data from gamified tasks (N = 208), from 4 different moments, were analyzed through multilevel linear modeling. Results suggested that there was a change in adolescents’ moral disengagement over time. Participants with greater empathy revealed lower moral disengagement overall. Over time, adolescents with greater empathy revealed lower moral disengagement within their own growth rate. Overall, our results provide important information about the dynamic relationship between moral disengagement, empathy and cyberbullying, which informs future studies and interventions.
Assessment of the axial resolution of a compact gamma camera with coded aperture collimator
Authors: Meißner Tobias , Cerbone Laura Antonia , Russo Paolo , Nahm Werner , Hesser Jürgen
Published: March 2024

Purpose

Handheld gamma cameras with coded aperture collimators are under investigation for intraoperative imaging in nuclear medicine. Coded apertures are a promising collimation technique for applications such as lymph node localization due to their high sensitivity and the possibility of 3D imaging. We evaluated the axial resolution and computational performance of two reconstruction methods.

Methods

An experimental gamma camera was set up consisting of the pixelated semiconductor detector Timepix3 and MURA mask of rank 31 with round holes of 0.08 mm in diameter in a 0.11 mm thick Tungsten sheet. A set of measurements was taken where a point-like gamma source was placed centrally at 21 different positions within the range of 12–100 mm. For each source position, the detector image was reconstructed in 0.5 mm steps around the true source position, resulting in an image stack. The axial resolution was assessed by the full width at half maximum (FWHM) of the contrast-to-noise ratio (CNR) profile along the z-axis of the stack. Two reconstruction methods were compared: MURA Decoding and a 3D maximum likelihood expectation maximization algorithm (3D-MLEM).

Results

While taking 4400 times longer in computation, 3D-MLEM yielded a smaller axial FWHM and a higher CNR. The axial resolution degraded from 5.3 mm and 1.8 mm at 12 mm to 42.2 mm and 13.5 mm at 100 mm for MURA Decoding and 3D-MLEM respectively.

Conclusion

Our results show that the coded aperture enables the depth estimation of single point-like sources in the near field. Here, 3D-MLEM offered a better axial resolution but was computationally much slower than MURA Decoding, whose reconstruction time is compatible with real-time imaging.
Deficient editorial practices, perceived quality, and expedient scholarly publishing in a developing nation
Authors: Bredan Amin , Tashani Osama , Bakoush Omran
Published: March 2024

Background There is increasing concern about the quality, integrity, and accessibility to research published in the developing world. This study explores the editorial practices and editors’ perspectives to gain insight into the standard of scholarly publishing in Libya. Methods Between 21st January and 12th February, 2022, the editors-in-chief (EC) of Libyan academic journals were invited to complete a questionnaire on editorial practices, degree of satisfaction with submitted and published manuscripts, review processes, and journal performance, as well as challenges facing the journals. Journal websites were examined for quality, and indexation coverage and citations were assessed. We examined the number of citations in Google Scholar for all 2019 articles published in each journal. Descriptive statistics were used to quantitatively summarize the data and thematic analysis was used for the narrative text. Results 48 EC completed the questionnaire. The EC was affiliated with the institution that owns the journal in 92% of cases. Most EC (83%) were satisfied with the peer-review quality, 69% believed that most of their published papers add new ideas or findings, and 96% were satisfied with their journal’s performance. However, despite the high degree of satisfaction, only one journal was indexed in Web of Science or Scopus and only 17% of the journals were indexed in Google Scholar. A qualitative assessment of journal websites revealed shortcomings in publishing practices in a large proportion of the journals. Conclusions The discordance between the satisfaction of the journal editors and the journal quality indicators points to a break in the quality system of Libyan academic publishing. Similar expedient publishing practices might exist in other countries as well. A comprehensive action plan led by academic institutions to enforce high standards for scholarly publishing is needed to advance research and high-quality scholarly publications in developing countries.