bluuebunny/crossref_metadata_2025 huggingface dataset:
Varicella zoster virus-associated non-necrotizing retinitis: case report
Authors: Rym Maamouri , Yasmine Houman , Marwa Abdelaziz , Imen Helal , Monia Cheour
Published: July 2023

Purpose

To describe clinical features and the course of a case of non-necrotizing herpetic retinitis secondary to Varicella zoster virus (VZV).

Materiel and methods

A single case report documented with multimodal imaging.

Results

A 52-year-old female patient with a past medical history of diabetes mellitus who presented with painful red right eye (OD). Ophthalmic examination showed perilimbal conjunctival nodule, granulomatous anterior uveitis, sectoral iris atrophy and increased intraocular pressure. Fundus examination in OD revealed posterior multifocal retinitis. Left eye examination was unremarkable. Polymerase chain reaction (PCR) of aqueous humor sample confirmed the presence of VZV DNA. Systemic antiviral therapy allowed the improvement of intraocular inflammation and disappearance of the retinal non necrotizing retinitis after one year of regular follow-up.

Conclusion

Non-necrotizing retinitis is an underdiagnosed form of VZV ocular infection.
AMEND: active module identification using experimental data and network diffusion
Authors: Boyd Samuel S. , Slawson Chad , Thompson Jeffrey A.
Published: July 2023

Background

Molecular interaction networks have become an important tool in providing context to the results of various omics experiments. For example, by integrating transcriptomic data and protein–protein interaction (PPI) networks, one can better understand how the altered expression of several genes are related with one another. The challenge then becomes how to determine, in the context of the interaction network, the subset(s) of genes that best captures the main mechanisms underlying the experimental conditions. Different algorithms have been developed to address this challenge, each with specific biological questions in mind. One emerging area of interest is to determine which genes are equivalently or inversely changed between different experiments. The equivalent change index (ECI) is a recently proposed metric that measures the extent to which a gene is equivalently or inversely regulated between two experiments. The goal of this work is to develop an algorithm that makes use of the ECI and powerful network analysis techniques to identify a connected subset of genes that are highly relevant to the experimental conditions.

Results

To address the above goal, we developed a method called Active Module identification using Experimental data and Network Diffusion (AMEND). The AMEND algorithm is designed to find a subset of connected genes in a PPI network that have large experimental values. It makes use of random walk with restart to create gene weights, and a heuristic solution to the Maximum-weight Connected Subgraph problem using these weights. This is performed iteratively until an optimal subnetwork (i.e., active module) is found. AMEND was compared to two current methods, NetCore and DOMINO, using two gene expression datasets.

Conclusion

The AMEND algorithm is an effective, fast, and easy-to-use method for identifying network-based active modules. It returned connected subnetworks with the largest median ECI by magnitude, capturing distinct but related functional groups of genes. Code is freely available athttps://github.com/samboyd0/AMEND.
Genome-wide identification, characterization and transcriptional profile of the SWEET gene family in Dendrobium officinale
Authors: Hao Li , Shi Xin , Qin Shunwang , Dong Jiahong , Shi Huan , Wang Yuehua , Zhang Yi
Published: July 2023

Background

Dendrobium officinale Kimura et Migo (D. officinale) is a well-known traditional Chinese medicine with high content polysaccharides in stems. The SWEET (Sugars Will Eventually be Exported Transporters) family is a novel class of sugar transporters mediating sugar translocation among adjacent cells of plants. The expression patterns of SWEETs and whether they are associated with stress response in D. officinale remains uncovered.

Results

Here, 25 SWEET genes were screened out from D. officinale genome, most of which typically contained seven transmembrane domains (TMs) and harbored two conserved MtN3/saliva domains. Using multi-omics data and bioinformatic approaches, the evolutionary relationship, conserved motifs, chromosomal location, expression patterns, correlationship and interaction network were further analyzed. DoSWEETs were intensively located in nine chromosomes. Phylogenetic analysis revealed that DoSWEETs were divided into four clades, and conserved motif 3 specifically existed in DoSWEETs from clade II. Different tissue-specific expression patterns of DoSWEETs suggested the division of their roles in sugar transport. In particular, DoSWEET5b, 5c, and 7d displayed relatively high expression levels in stems. DoSWEET2b and 16 were significantly regulated under cold, drought, and MeJA treatment, which were further verified using RT-qPCR. Correlation analysis and interaction network prediction discovered the internal relationship of DoSWEET family.

Conclusions

Taken together, the identification and analysis of the 25 DoSWEETs in this study provide basic information for further functional verification in D. officinale.
Comparative genomics reveals insights into anuran genome size evolution
Authors: Zuo Bin , Nneji Lotanna Micah , Sun Yan-Bo
Published: July 2023

Background

Amphibians, particularly anurans, display an enormous variation in genome size. Due to the unavailability of whole genome datasets in the past, the genomic elements and evolutionary causes of anuran genome size variation are poorly understood. To address this, we analyzed whole-genome sequences of 14 anuran species ranging in size from 1.1 to 6.8 Gb. By annotating multiple genomic elements, we investigated the genomic correlates of anuran genome size variation and further examined whether the genome size relates to habitat types.

Results

Our results showed that intron expansions or contraction and Transposable Elements (TEs) diversity do not contribute significantly to genome size variation. However, the recent accumulation of transposable elements (TEs) and the lack of deletion of ancient TEs primarily accounted for the evolution of anuran genome sizes. Our study showed that the abundance and density of simple repeat sequences positively correlate with genome size. Ancestral state reconstruction revealed that genome size exhibits a taxon-specific pattern of evolution, with families Bufonidae and Pipidae experiencing extreme genome expansion and contraction events, respectively. Our result showed no relationship between genome size and habitat types, although large genome-sized species are predominantly found in humid habitats.

Conclusions

Overall, our study identified the genomic element and their evolutionary dynamics accounting for anuran genome size variation, thus paving a path to a greater understanding of the size evolution of the genome in amphibians.
Genome-wide identification of SrbHLH transcription factors highlights its potential role in rebaudioside A (RA) biosynthesis in Stevia rebaudiana
Authors: Li Yuping , Qiu Yuan , Xu Xin , Luo Ming
Published: July 2023

Stevia rebaudiana Bertoni is a valuable medicinal plant and an essential source of natural sweetener, steviol glycosides (SGs), with rebaudioside A (RA) being one of the main components of SGs. bHLH transcription factors play a crucial role in plant development and secondary metabolism. In this study, 159 SrbHLH genes were identified from the S. rebaudiana genome, and each gene was named based on its chromosome location. The SrbHLH proteins were then clustered into 18 subfamilies through phylogenetic analysis. The analysis of conserved motifs and gene structure further supported the classification of the SrbHLH family. Chromosomal location and gene duplication events of SrbHLH genes were also studied. Moreover, based on the RNA-Seq data of different tissues of S. rebaudiana, 28 SrbHLHs were co-expressed with structural genes involved in RA biosynthesis. The expression pattern of candidate SrbHLH genes were confirmed by qPCR. Finally, dual luciferase reporter assays (DLAs) and subcellular localization analysis verified SrbHLH22, SrbHLH111, SrbHLH126, SrbHLH142, and SrbHLH152 are critical regulators of RA biosynthesis. This study provides new insights into the function of SrbHLHs in regulating SGs biosynthesis and lays the foundation for future applications of SrbHLH genes in molecular breeding of S. rebaudiana.
A wide range of missing imputation approaches in longitudinal data: a simulation study and real data analysis
Authors: Jahangiri Mina , Kazemnejad Anoshirvan , Goldfeld Keith S. , Daneshpour Maryam S. , Mostafaei Shayan , Khalili Davood , Moghadas Mohammad Reza , Akbarzadeh Mahdi
Published: July 2023

Background

Missing data is a pervasive problem in longitudinal data analysis. Several single-imputation (SI) and multiple-imputation (MI) approaches have been proposed to address this issue. In this study, for the first time, the function of the longitudinal regression tree algorithm as a non-parametric method after imputing missing data using SI and MI was investigated using simulated and real data.

Method

Using different simulation scenarios derived from a real data set, we compared the performance of cross, trajectory mean, interpolation, copy-mean, and MI methods (27 approaches) to impute missing longitudinal data using parametric and non-parametric longitudinal models and the performance of the methods was assessed in real data. The real data included 3,645 participants older than 18 years within six waves obtained from the longitudinal Tehran cardiometabolic genetic study (TCGS). The data modeling was conducted using systolic and diastolic blood pressure (SBP/DBP) as the outcome variables and included predictor variables such as age, gender, and BMI. The efficiency of imputation approaches was compared using mean squared error (MSE), root-mean-squared error (RMSE), median absolute deviation (MAD), deviance, and Akaike information criteria (AIC).

Results

The longitudinal regression tree algorithm outperformed based on the criteria such as MSE, RMSE, and MAD than the linear mixed-effects model (LMM) for analyzing the TCGS and simulated data using the missing at random (MAR) mechanism. Overall, based on fitting the non-parametric model, the performance of the 27 imputation approaches was nearly similar. However, the SI traj-mean method improved performance compared with other imputation approaches.

Conclusion

Both SI and MI approaches performed better using the longitudinal regression tree algorithm compared with the parametric longitudinal models. Based on the results from both the real and simulated data, we recommend that researchers use the traj-mean method for imputing missing values of longitudinal data. Choosing the imputation method with the best performance is widely dependent on the models of interest and the data structure.
Acute myeloma kidney and SARS-COV2 infection with dialysis need: never say never - a case report
Authors: Donati Gabriele , Przygocka Agnieszka , Zappulo Fulvia , Vischini Gisella , Valente Sabrina , La Manna Gaetano
Published: July 2023

Background

Older individuals with multiple comorbidities and especially patients with multiple myeloma are at higher risk of contracting SARS-CoV-2. When patients with multiple myeloma (MM) are also affected by SARS-CoV-2 the time to start immunosuppressants is still a clinical dilemma especially when urgent hemodialysis is required for acute kidney injury (AKI).

Case presentation

We present a case of an 80-year-old woman who was diagnosed with AKI in MM. The patient began hemodiafiltration (HDF) with free light chain removal combined with bortezomib and dexamethasone. The reduction of free light chains concurrently was obtained by means of HDF using poly ester polymer alloy (PEPA) high-flux filter: 2 PEPA filters were used in series during each 4-h length HDF session. A total of 11 sessions was carried out. The hospitalization was complicated with acute respiratory failure caused by SARS-CoV-2 pneumonia successfully treated with both pharmacotherapy and respiratory support. Once the respiratory status stabilized MM treatment was resumed.

The patient was discharged in stable condition after 3 months of hospitalization. The follow up showed significant improvement of the residual renal function which allowed interruption of hemodialysis (HD).

Conclusions

The complexity of patients affected by MM, AKI, and SARS-CoV-2 should not discourage the attending physicians to offer the adequate treatment. The cooperation of different specialists can lead to a positive outcome in those complicated cases.
Assessing awareness of blood cancer symptoms and barriers to symptomatic presentation: measure development and results from a population survey in the UK
Authors: Boswell Laura , Harris Jenny , Ip Athena , Russell Jessica , Black Georgia B , Whitaker Katriina L
Published: July 2023

Background

Low levels of cancer awareness may contribute to delays in seeking medical help and subsequent delays in diagnosis. For blood cancer this may be a particularly prominent problem due to the high prevalence of undifferentiated symptoms such as bodily pain, weakness, nausea and weight loss, resulting in low symptom awareness. The delay is exacerbated by the dismissal of similar symptoms which are often interpreted as mild disease, resulting in multiple consultations prior to diagnosis. This study describes the development of a Cancer Awareness Measure for Blood Cancer (Blood CAM) and presents results from a population-representative survey using the measure.

Methods

A rapid systematic review identified constructs relevant to blood cancer. Items were taken from previous awareness measures and other literature and reviewed by expert groups including health care professionals and patients. Cognitive interviews were conducted with ten members of the public to check comprehension and clarity. A total sample of 434 participants completed the survey at Time 1 and n = 302 at Time 2 (two weeks later).

Results

Internal reliability was high across the different constructs included in the questionnaire (> 0.70) and test-retest reliability was moderate to good (0.49–0.79). The most commonly recognised blood cancer symptoms were unexplained weight loss (68.9%) and unexplained bleeding (64.9%) and the least commonly recognised symptoms were night sweats (31.3%) breathlessness and rash/itchy skin (both 44%). In terms of symptom experience, fatigue was the most commonly reported symptom (26.7%) followed by night sweats (25.4%). Exploratory factor analysis of barriers to presenting at primary care revealed three distinct categories of barriers; emotional, external/practical and service/healthcare professional related. Service and emotional barriers were most common.

Conclusions

We developed a valid and reliable tool to assess blood cancer awareness and showed variable awareness of blood cancer symptoms which can help target public health campaigns. We also incorporated additional measures (e.g. confidence to re-consult, ability to understand symptoms) that could be used to tailor public messaging for blood cancer and for other harder to suspect and diagnose cancers.
The impact of dyslipidemia on lumbar intervertebral disc degeneration and vertebral endplate modic changes: a cross-sectional study of 1035 citizens in China
Authors: Yuan Liang , Huang Zhengqi , Han Weitao , Chang Ruiming , Sun Bo , Zhu Mingxi , Li Chenjing , Yan Jiansen , Liu Bin , Yin Haidong , Ye Wei
Published: July 2023

Background

Intervertebral disc degeneration (IDD) and vertebral endplate Modic changes (MCs) are common lumbar degenerative phenotypes related to low back pain (LBP). Dyslipidemia has been linked to LBP but its associations with IDD and MCs have not been fully elucidated. The present study aimed to address the possible link between dyslipidemia, IDD and MCs in the Chinese population.

Methods

1035 citizens were enrolled in the study. The levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were collected. IDD was evaluated based on the Pfirrmann grading system and subjects with an average grade ≥ 3 were defined as having degeneration. MCs were classified into typical types 1, 2 and 3. Covariables, including age, sex, BMI and fasting plasma glucose, were included for the adjustment of the logistic analyses.

Results

The degeneration group included 446 subjects while the nondegeneration group included 589 subjects. The degeneration group had significant higher levels of TC and LDL-C (p < 0.001) whereas TG and HDL-C were not significantly different between the two groups. TC and LDL-C concentrations were significantly positively correlated with average IDD grades (p < 0.001). Multivariate logistic regression revealed that high TC (≥ 6.2 mmol/L, adjusted OR = 1.775, 95% CI = 1.209–2.606) and high LDL-C (≥ 4.1 mmol/L, adjusted OR = 1.818, 95% CI = 1.123–2.943) were independent risk factors for IDD. Type 1 MC presented in 84 (8.12%) subjects, type 2 MC presented in 244 (23.57%) subjects, type 3 MC presented in 27 (2.61%) subjects and no MC was observed in the remaining 680 (65.70%) subjects. The type 2 MC group demonstrated a higher level of TC, but the association between serum lipids and MCs could not be confirmed in further multivariate logistic regression.

Conclusions

High TC (≥ 6.2 mmol/L) and LDL-C (≥ 4.1 mmol/L) concentrations were independent risk factors for IDD for citizens in China. However, the association between dyslipidemia and MCs could not be determined. The effect of excess serum cholesterol may be critical for IDD and cholesterol lowering treatment may provide new opportunities in the management of lumbar disc degeneration.
Surgical Apgar Score can accurately predict the severity of post-operative complications following emergency laparotomy
Authors: Kyaruzi Victor Meza , Chamshama Douglas E. , Khamisi Ramadhani H. , Akoko Larry O.
Published: July 2023

Background

The Surgical Apgar Score (SAS) describes a feasible and objective tool for predicting surgical outcomes. However, the accuracy of the score and its correlation with the complication severity has not been well established in many grounds of low resource settings.

Objective

To determine the accuracy of Surgical Apgar Score in predicting the severity of post-operative complications among patients undergoing emergency laparotomy at Muhimbili National Hospital.

Methods

A prospective cohort study was conducted for a period of 12 months; patients were followed for 30 days, the risk of complication was classified using the Surgical Apgar Score (SAS), severity of complication was estimated using the Clavien Dindo Classification (CDC) grading scheme and Comprehensive Complication Index (CCI). Spearman correlation and simple linear regression statistic models were applied to establish the relationship between Surgical Apgar Score (SAS) and Comprehensive Complication Index (CCI). The Accuracy of SAS was evaluated by determining its discriminatory capacity on Receiver Operating Characteristics (ROC) curve, data normality was tested by Shapiro–Wilk statistic 0.929 (p < 0.001).Analysis was done using International Business Machine Statistical Product and Service Solution (IBM SPSS) version 27.

Results

Out of the 111 patients who underwent emergency laparotomy, 71 (64%) were Male and the median age (IQR) was 49 (36, 59).The mean SAS was 4.86 (± 1.29) and the median CCI (IQR) was 36.20 (26.2, 42.40). Patients in the high-risk SAS group (0–4) were more likely to experience severe and life-threatening complications, with a mean CCI of 53.3 (95% CI: 47.2–63.4), compared to the low-risk SAS group (7–10) with a mean CCI of 21.0 (95% CI: 5.3–36.2). A negative correlation was observed between SAS and CCI, with a Spearman r of -0.575 (p < 0.001) and a regression coefficient b of -11.5 (p < 0.001). The SAS demonstrated good accuracy in predicting post-operative complications, with an area under the curve of 0.712 (95% CI: 0.523–0.902, p < 0.001) on the ROC.

Conclusion

This study has demonstrated that SAS can accurately predict the occurrence of complications following emergency laparotomy at Muhimbili National Hospital.
Continuing professional development (CPD) system development, implementation, evaluation and sustainability for healthcare professionals in low- and lower-middle-income countries: a rapid scoping review
Authors: Merry Lisa , Castiglione Sonia Angela , Rouleau Geneviève , Létourneau Dimitri , Larue Caroline , Deschênes Marie-France , Gonsalves Dolly Maria , Ahmed Lubana
Published: July 2023

Background

Policymakers and program developers in low-and lower-middle-income countries (LLMICs) are increasingly seeking evidence-based information and guidance on how to successfully develop and implement continuing professional development (CPD) systems. We conducted a rapid scoping review to map and synthesize what is known regarding the development, implementation, evaluation and sustainability of CPD systems for healthcare professionals in LLMICs.

Methods

We searched MEDLINE, CINAHL and Web of Science. Reference lists were screened and a cited reference search of included articles was conducted. Supplementary information on the CPD systems identified in the articles was also identified via an online targeted grey literature search. English, French and Spanish literature published from 2011 to 2021 were considered. Data were extracted and combined and summarized according to country/region and healthcare profession via tables and narrative text.

Results

We included 15 articles and 23 grey literature sources. Africa was the region most represented followed by South and Southeast Asia and the Middle East. The literature most often referred to CPD systems for nurses and midwives; CPD systems for physicians were frequently referred to as well. Findings show that leadership and buy-in from key stakeholders, including government bodies and healthcare professional organizations, and a framework are essential for the development, implementation and sustainability of a CPD system in a LLMIC. The guiding framework should incorporate a regulatory perspective, as well as a conceptual lens (that informs CPD objectives and methods), and should consider contextual factors (support for CPD, healthcare context and population health needs). In terms of important steps to undertake, these include: a needs assessment; drafting of a policy, which details the regulations (laws/norms), the CPD requirements and an approach for monitoring, including an accreditation mechanism; a financing plan; identification and production of appropriate CPD materials and activities; a communication strategy; and an evaluation process.

Conclusion

Leadership, a framework and a clearly delineated plan that is responsive to the needs and context of the setting, are essential for the development, implementation and sustainability of a CPD system for healthcare professionals in a LLMIC.
FHIR-PYrate: a data science friendly Python package to query FHIR servers
Authors: Hosch René , Baldini Giulia , Parmar Vicky , Borys Katarzyna , Koitka Sven , Engelke Merlin , Arzideh Kamyar , Ulrich Moritz , Nensa Felix
Published: July 2023

Background

We present FHIR-PYrate, a Python package to handle the full clinical data collection and extraction process. The software is to be plugged into a modern hospital domain, where electronic patient records are used to handle the entire patient’s history. Most research institutes follow the same procedures to build study cohorts, but mainly in a non-standardized and repetitive way. As a result, researchers spend time writing boilerplate code, which could be used for more challenging tasks.

Methods

The package can improve and simplify existing processes in the clinical research environment. It collects all needed functionalities into a straightforward interface that can be used to query a FHIR server, download imaging studies and filter clinical documents. The full capacity of the search mechanism of the FHIR REST API is available to the user, leading to a uniform querying process for all resources, thus simplifying the customization of each use case. Additionally, valuable features like parallelization and filtering are included to make it more performant.

Results

As an exemplary practical application, the package can be used to analyze the prognostic significance of routine CT imaging and clinical data in breast cancer with tumor metastases in the lungs. In this example, the initial patient cohort is first collected using ICD-10 codes. For these patients, the survival information is also gathered. Some additional clinical data is retrieved, and CT scans of the thorax are downloaded. Finally, the survival analysis can be computed using a deep learning model with the CT scans, the TNM staging and positivity of relevant markers as input. This process may vary depending on the FHIR server and available clinical data, and can be customized to cover even more use cases.

Conclusions

FHIR-PYrate opens up the possibility to quickly and easily retrieve FHIR data, download image data, and search medical documents for keywords within a Python package. With the demonstrated functionality, FHIR-PYrate opens an easy way to assemble research collectives automatically.
Xanthine oxidoreductase gene polymorphisms are associated with high risk of sepsis and organ failure
Authors: Gao Li , Rafaels Nicholas , Dudenkov Tanda M. , Damarla Mahendra , Damico Rachel , Maloney James P. , Moss Marc , Martin Greg S. , Sevransky Jonathan , Shanholtz Carl , Herr Dan L. , Garcia Joe G.N. , Hernandez-Beeftink Tamara , Villar Jesús , Flores Carlos , Beaty Terri H. , Brower Roy , Hassoun Paul M. , Barnes Kathleen C.
Published: July 2023

Background

Sepsis and associated organ failures confer substantial morbidity and mortality. Xanthine oxidoreductase (XOR) is implicated in the development of tissue oxidative damage in a wide variety of respiratory and cardiovascular disorders including sepsis and sepsis-associated acute respiratory distress syndrome (ARDS). We examined whether single nucleotide polymorphisms (SNPs) in the XDH gene (encoding XOR) might influence susceptibility to and outcome in patients with sepsis.

Methods

We genotyped 28 tag SNPs in XDH gene in the CELEG cohort, including 621 European American (EA) and 353 African American (AA) sepsis patients. Serum XOR activity was measured in a subset of CELEG subjects. Additionally, we assessed the functional effects of XDH variants utilizing empirical data from different integrated software tools and datasets.

Results

Among AA patients, six intronic variants (rs206805, rs513311, rs185925, rs561525, rs2163059, rs13387204), in a region enriched with regulatory elements, were associated with risk of sepsis (P < 0.008–0.049). Two out of six SNPs (rs561525 and rs2163059) were associated with risk of sepsis-associated ARDS in an independent validation cohort (GEN-SEP) of 590 sepsis patients of European descent. Two common SNPs (rs1884725 and rs4952085) in tight linkage disequilibrium (LD) provided strong evidence for association with increased levels of serum creatinine (Padjusted<0.0005 and 0.0006, respectively), suggesting a role in increased risk of renal dysfunction. In contrast, among EA ARDS patients, the missense variant rs17011368 (I703V) was associated with enhanced mortality at 60-days (P < 0.038). We found higher serum XOR activity in 143 sepsis patients (54.5 ± 57.1 mU/mL) compared to 31 controls (20.9 ± 12.4 mU/mL, P = 1.96 × 10− 13). XOR activity was associated with the lead variant rs185925 among AA sepsis patients with ARDS (P < 0.005 and Padjusted<0.01). Multifaceted functions of prioritized XDH variants, as suggested by various functional annotation tools, support their potential causality in sepsis.

Conclusions

Our findings suggest that XOR is a novel combined genetic and biochemical marker for risk and outcome in patients with sepsis and ARDS.
Both LDL and HDL particle concentrations associate positively with an increased risk of developing microvascular complications in patients with type 2 diabetes: lost protection by HDL (Zodiac-63)
Authors: Bourgonje Arno R. , Connelly Margery A. , van Goor Harry , van Dijk Peter R. , Dullaart Robin P. F.
Published: July 2023

Background

Triglyceride-rich lipoproteins (TRL) and low-density lipoproteins (LDL) are associated positively whereas high-density lipoproteins (HDL) are associated inversely with the development of new-onset type 2 diabetes (T2D). Here we studied potential associations between these lipoprotein particle concentrations and the risk of developing microvascular complications in patients with established T2D.

Methods

Lipoprotein particle concentrations (TRLP, LDLP, and HDLP) were determined in 278 patients with T2D participating in a primary care-based longitudinal cohort study (Zwolle Outpatient Diabetes project Integrating Available Care [ZODIAC] study) leveraging the Vantera nuclear magnetic resonance (NMR) platform using the LP4 algorithm. Associations between lipoprotein particles and incident microvascular complications (nephropathy, neuropathy, and retinopathy) were assessed using Cox proportional hazards regression models.

Results

In total, 136 patients had microvascular complications at baseline. During a median follow-up of 3.2 years, 49 (34.5%) of 142 patients without microvascular complications at baseline developed new-onset microvascular complications. In multivariable Cox proportional hazards regression analyses, both total LDLP and HDLP concentrations, but not total TRLP concentrations, were positively associated with an increased risk of developing any microvascular complications after adjustment for potential confounding factors, including age, sex, disease duration, HbA1c levels, history of macrovascular complications, and statin use (adjusted hazard ratio [HR] per 1 SD increment: 1.70 [95% CI 1.24–2.34], P < 0.001 and 1.63 [95% CI 1.19–2.23], P = 0.002, respectively). When analyzing each microvascular complication individually, total LDLP concentrations were positively associated with retinopathy (adjusted HR 3.35, 95% CI 1.35–8.30, P = 0.009) and nephropathy (adjusted HR 2.13, 95% CI 1.27–3.35, P = 0.004), and total HDLP concentrations with neuropathy (adjusted HR 1.77, 95% CI 1.15–2.70, P = 0.009). No significant associations were observed for lipoprotein particle subfractions.

Conclusions

Total lipoprotein particle concentrations of both LDL and HDL associate positively with an increased risk of developing microvascular complications in T2D. We propose that the protective role of HDL on the development of microvascular complications may be lost in established T2D.
Genetic association between the APOE ε4 allele, toxicant exposures and Gulf war illness diagnosis
Authors: Abdullah L , Nkiliza A , Niedospial D , Aldrich G , Bartenfelder G , Keegan A , Hoffmann M , Mullan M , Klimas N , Baraniuk J , Crawford F , Krengel M , Chao L , Sullivan K
Published: July 2023

Introduction

Exposure to nerve agents, pyridostigmine bromide (PB), pesticides, and oil-well fires during the 1991 Gulf War (GW) are major contributors to the etiology of Gulf War Illness (GWI). Since the apolipoprotein E (APOE) ε4 allele is associated with the risk of cognitive decline with age, particularly in the presence of environmental exposures, and cognitive impairment is one of the most common symptoms experienced by veterans with GWI, we examined whether the ε4 allele was associated with GWI.

Methods

Using a case-control design, we obtained data on APOE genotypes, demographics, and self-reported GW exposures and symptoms that were deposited in the Boston Biorepository and Integrative Network (BBRAIN) for veterans diagnosed with GWI (n = 220) and healthy GW control veterans (n = 131). Diagnosis of GWI was performed using the Kansas and/or Center for Disease Control (CDC) criteria.

Results

Age- and sex-adjusted analyses showed a significantly higher odds ratio for meeting the GWI case criteria in the presence of the ε4 allele (Odds ratio [OR] = 1.84, 95% confidence interval [CI = 1.07–3.15], p ≤ 0.05) and with two copies of the ε4 allele (OR = 1.99, 95% CI [1.23–3.21], p ≤ 0.01). Combined exposure to pesticides and PB pills (OR = 4.10 [2.12–7.91], p ≤ 0.05) as well as chemical alarms and PB pills (OR = 3.30 [1.56–6.97] p ≤ 0.05) during the war were also associated with a higher odds ratio for meeting GWI case criteria. There was also an interaction between the ε4 allele and exposure to oil well fires (OR = 2.46, 95% CI [1.07–5.62], p ≤ 0.05) among those who met the GWI case criteria.

Conclusion

These findings suggest that the presence of the ε4 allele was associated with meeting the GWI case criteria. Gulf War veterans who reported exposure to oil well fires and have an ε4 allele were more likely to meet GWI case criteria. Long-term surveillance of veterans with GWI, particularly those with oil well fire exposure, is required to better assess the future risk of cognitive decline among this vulnerable population.
Impact of a diabetes pay-for-performance program on nonincentivized mental disorders: a panel study based on claims database analysis
Authors: Sung Ming-Chan , Chung Kuo-Piao , Cheng Shou-Hsia
Published: July 2023

Background

Diabetes is one of the most prevalent chronic diseases with subsequent complications. The positive effects of diabetes pay-for-performance (P4P) programs on treatment outcomes have been reported. The program provides financial incentives based on physiological care indicators, but common mental disorder complications such as depression are not covered.

Methods

This study employed a natural experimental design to examine the spillover effects of diabetes P4P program on patients with nonincentivized depressive symptoms. The intervention group consisted of diabetes patients enrolled in the DM P4P program from 2010 to 2015. Unenrolled patients were selected by propensity score matching to form the comparison group. Difference-in-differences analyses were conducted to evaluate the effects of P4P programs. We employed generalized estimating equation (GEE) models, difference-in-differences analyses and difference-in-difference-in-differences analyses to evaluate the net effect of diabetes P4P programs. Changes in medical expenses (outpatient and total health care costs) over time were analysed for the treatment and comparison groups.

Results

The results showed that enrolled patients had a higher incidence of depressive symptoms than unenrolled patients. The outpatient and total care expenses of diabetes patients with depressive symptoms were lower in the intervention group than in the comparison group. Diabetes patients with depressive symptoms enrolled in the DM P4P program had lower expenses for depression-related care than those not enrolled in the program.

Conclusions

The DM P4P program benefits diabetes patients by screening for depressive symptoms and lowering accompanying health care expenses. These positive spillover effects may be an important aspect of physical and mental health in patients with chronic disease enrolled in disease management programs while contributing to the control of health care expenses for chronic diseases.
Replacing of sedentary behavior with physical activity and the risk of mortality in people with prediabetes and diabetes: a prospective cohort study
Authors: Zhu Ping , Lao Guojuan , Li Huipeng , Tan Rongshao , Gu Jing , Ran Jianmin
Published: July 2023

Background

Sedentary behavior is prevalent among people with diabetes and is associated with unfavorable cardiometabolic health. However, there is limited evidence regarding the impact of replacing sedentary time (ST) with physical activity on mortality in people with prediabetes and diabetes. We prospectively examined the association between accelerometer-measured ST and mortality among people with prediabetes and diabetes after adjusting for demographic characteristics, lifestyle factors, and moderate- to vigorous-intensity PA (MVPA). We further determined the effect of replacing ST with equal time of different types of physical activities on all-cause mortality.

Methods

We included 1242 adults with prediabetes and 1037 with diabetes from the National Health and Nutrition Examination Survey. Restricted cubic splines were fitted to determine the dose–response association between ST and overall mortality. Isotemporal substitution modeling was used to explore the hazard ratio (HR) effects of ST replacement.

Results

During a median follow-up of 14.1 years, 424 adults with prediabetes and 493 with diabetes died. Compared with the lowest tertile of ST, the multivariable-adjusted HRs for all-cause mortality in the highest tertile were 1.76 (95% confidence interval [CI] 1.19, 2.60) for participants with prediabetes and 1.76 (1.17, 2.65) for those with diabetes. Additionally, a linear association between ST and all-cause mortality was observed in adults with prediabetes and diabetes, with HRs for each 60 min/day increment in ST of 1.19 (1.10, 1.30) and 1.25 (1.12, 1.40), respectively. Isotemporal substitution results indicated that individuals with prediabetes whose ST was replaced by 30 min of light-intensity physical activity (LPA) and MVPA had 9% and 40% lower all-cause mortality, respectively. In people with diabetes, replacing sedentary behavior with an equivalent time of LPA and MVPA was also associated with mortality risk reduction (HR 0.89; 95% CI 0.84, 0.95 for LPA; HR 0.73; 95% CI 0.49, 1.11 for MVPA).

Conclusions

Higher ST was associated in a dose–response manner with an increased risk of premature mortality among adults with prediabetes and diabetes. Statistically replacing ST with LPA was potentially beneficial for health in this high-risk population.
Aberrant KAT2A accumulations render TRIM22-low melanoma sensitive to Notch1 inhibitors via epigenetic reprogramming
Authors: Gu Xiaoli , Min Wei , Zeng Yibin , Fan Ni , Qian Qihong
Published: July 2023

Background

Aberrant ubiquitin-proteasome system (UPS) triggers various disorders of biological events and contributes to progression of tumorigenesis. The tripartite motif containing 22 (TRIM22) was demonstrated to participate in the progression of multiple malignancies. Nevertheless, the role of TRIM22 in melanoma is still indefinite. This project aims to investigate the biological function of TRIM22 in melanoma and provide novel therapeutical targets.

Methods

Bioinformatic algorithms were used to investigate prognostic significance of TRIM22. The in vitro or in vivo assays were used to explore the functions of TRIM22 in melanoma. The Co-Immunoprecipitation (Co-IP) and in vivo ubiquitination assays were used to assess regulations of TRIM22 on lysine acetyltransferase 2 A (KAT2A). The Chromatin immunoprecipitation (ChIP) assays and luciferase reporter assay were utilized to explore epigenetic regulations of KAT2A on Notch1.

Results

Here, we utilized the bioinformatic methods to confirm that TRIM22 is decreased in melanoma than normal tissues. Patients with low TRIM22 levels had shorter survival months than those with high TRIM22 levels. Targeting TRIM22 favors melanoma cell migration, proliferation, and tumor development in vitro and in vivo. Mechanistically, TRIM22 interacts with KAT2A and promotes its degradation in a ubiquitination-dependent manner. Melanoma cells with TRIM22 deficiency depended on KAT2A to enhance malignant progression, including proliferation, migration, and in vivo growth. KEGG analysis determined the positive correlation between KAT2A and Notch signaling. Chromatin Immunoprecipitation (ChIP) assays implicated that KAT2A directly binds to the promoter region of Notch1 and mediates the enrichment of H3K9ac modification. KAT2A activates Notch1 transcriptional levels and sustains the stemness feature of melanoma cells. Nocth1 inhibitor (IMR-1) effectively suppresses the growth of TRIM22low melanoma in vitro and in vivo but fails to inhibit TRIM22high melanoma.

Conclusion

Together, our study illustrates the mechanism by which the TRIM22-KAT2A-Notch1 axis promotes melanoma progression, and demonstrates that KAT2A/Nocth1 confers an epigenetic vulnerability in TRIM22low melanoma.
The role of universal health coverage and global health security nexus and interplay on SARS-CoV-2 infection and case-fatality rates in Africa : a structural equation modeling approach
Authors: Biadgilign Sibhatu , Hailu Alemayehu , Gebremichael Bereket , Letebo Mekitew , Berhanesilassie Etsub , Shumetie Arega
Published: July 2023

Background

The Coronavirus Disease (COVID-19) caused by SARS-CoV-2 infections remains a significant health challenge worldwide. There is paucity of evidence on the influence of the universal health coverage (UHC) and global health security (GHS) nexus on SARS-CoV-2 infection risk and outcomes. This study aimed to investigate the effects of UHC and GHS nexus and interplay on SARS-CoV-2 infection rate and case-fatality rates (CFR) in Africa.

Methods

The study employed descriptive methods to analyze the data drawn from multiple sources as well used structural equation modeling (SEM) with maximum likelihood estimation to model and assess the relationships between independent and dependent variables by performing path analysis.

Results

In Africa, 100% and 18% of the effects of GHS on SARS-CoV-2 infection and RT-PCR CFR, respectively were direct. Increased SARS-CoV-2 CFR was associated with median age of the national population (β = -0.1244, [95% CI: -0.24, -0.01],P = 0.031 ); COVID-19 infection rate (β = -0.370, [95% CI: -0.66, -0.08],P = 0.012 ); and prevalence of obesity among adults aged 18 + years (β = 0.128, [95% CI: 0.06,0.20],P = 0.0001) were statistically significant. SARS-CoV-2 infection rates were strongly linked to median age of the national population (β = 0.118, [95% CI: 0.02,0.22 ],P = 0.024); population density per square kilometer, (β = -0.003, [95% CI: -0.0058, -0.00059],P = 0.016 ) and UHC for service coverage index (β = 0.089, [95% CI: 0.04,0.14,P = 0.001 ) in which their relationship was statistically significant.

Conclusions

The study shade a light that UHC for service coverage, and median age of the national population, population density have significant effect on COVID-19 infection rate while COVID-19 infection rate, median age of the national population and prevalence of obesity among adults aged 18 + years were associated with COVID-19 case-fatality rate. Both, UHC and GHS do not emerge to protect against COVID-19-related case fatality rate.
Probability of sporadic lymphangioleiomyomatosis in women presenting with spontaneous pneumothorax
Authors: Suter Audrey , Müller Marie-Eve , Daccord Cécile , Taffé Patrick , Lazor Romain
Published: July 2023

Background

Sporadic lymphangioleiomyomatosis (S-LAM) is a rare low-grade neoplasm of young women characterized by multiple pulmonary cysts leading to progressive dyspnea and recurrent spontaneous pneumothorax (SP). The diagnosis of S-LAM may be delayed by several years. To reduce this delay, chest computed tomography (CT) screening has been proposed to uncover cystic lung disease in women presenting with SP. However, the probability to discover S-LAM in this population has not been determined precisely. The aim of this study was to calculate the probability of finding S-LAM in women presenting with (a) SP, and (b) apparent primary SP (PSP) as first manifestation of S-LAM.

Methods

Calculations were made by applying the Bayes theorem to published epidemiological data on S-LAM, SP and PSP. Each term of the Bayes equation was determined by meta-analysis, and included: (1) the prevalence of S-LAM in the general female population, (2) the incidence rate of SP and PSP in the general female population, and (3) the incidence rate of SP and apparent PSP in women with S-LAM.

Results

The prevalence of S-LAM in the general female population was 3.03 per million (95% confidence interval 2.48, 3.62). The incidence rate of SP in the general female population was 9.54 (8.15, 11.17) per 100,000 person-years (p-y). The incidence rate of SP in women with S-LAM was 0.13 (0.08, 0.20). By combining these data in the Bayes theorem, the probability of finding S-LAM in women presenting with SP was 0.0036 (0.0025, 0.0051). For PSP, the incidence rate in the general female population was 2.70 (1.95, 3.74) per 100,000 p-y. The incidence rate of apparent PSP in women with S-LAM was 0.041 (0.030, 0.055). With the Bayes theorem, the probability of finding S-LAM in women presenting with apparent PSP as first disease manifestation was 0.0030 (0.0020, 0.0046). The number of CT scans to perform in women to find one case of S-LAM was 279 for SP and 331 for PSP.

Conclusion

The probability of discovering S-LAM at chest CT in women presenting with apparent PSP as first disease manifestation was low (0.3%). Recommending chest CT screening in this population should be reconsidered.
Plasma protein biomarkers reflective of the host response in patients developing Intensive Care Unit-acquired pneumonia
Authors: van Engelen Tjitske S. R. , Reijnders Tom D. Y. , Paling Fleur P. , Bonten Marc J. M. , Timbermont Leen , Malhotra-Kumar Surbhi , Kluytmans Jan A. J. W. , Peters-Sengers Hessel , van der Poll Tom ,   for the ASPIRE-I. C. U. Study Team, Wolkewitz Martin , Ali Omar , Ruzin Alexey , Timbermont Leen , Lammens Christine , Hullegie Sebastiaan , Troeman Darren , van Hout Denise , Prins Daniël , Kalyani Rubana , Eickhoff Mark , Shoemaker Kathryn , Vilken Tuba , Vlaeminck Jelle , Coppens Jasmine , van der Schalk Thomas , Xavier Basil Britto , Odisseeva Evelina , Vatcheva Rossitza , Drab Michal , Vajter Jaromir , Tamme Kadri , Fartoukh Muriel , LePape Alain , Landais Mickael , Plantefève Gaetan , Tacconelli Evelina , Kaasch Achim , Jurkinya Róbert , Zsolt Iványi , van Rijen Miranda , Cremer Olaf , Carevic Biljana , Jevdjić Jasna , Escudero Dolores , Garcia Miguel Sanchez , Prat-Aymerich Cristina , Suberviola-Cañas Borja , Arenzana-Seisdedos Angel , Bodur Hürrem , Kirakli Cenk , Bozkurt Ilkay , Long Sandra
Published: July 2023

Background

Immune suppression has been implicated in the occurrence of pneumonia in critically ill patients. We tested the hypothesis that Intensive Care Unit (ICU)-acquired pneumonia is associated with broad host immune aberrations in the trajectory to pneumonia, encompassing inflammatory, endothelial and coagulation responses. We compared plasma protein biomarkers reflecting the systemic host response in critically ill patients who acquire a new pneumonia (cases) with those who do not (controls).

Methods

We performed a nested case–control study in patients undergoing mechanical ventilation at ICU admission with an expected stay of at least 48 h enrolled in 30 hospitals in 11 European countries. Nineteen host response biomarkers reflective of key pathophysiological domains were measured in plasma obtained on study inclusion and day 7, and—in cases—on the day of pneumonia diagnosis.

Results

Of 1997 patients, 316 developed pneumonia (15.8%) and 1681 did not (84.2%). Plasma protein biomarker analyses, performed in cases and a randomly selected subgroup of controls (1:2 ratio to cases, n = 632), demonstrated considerable variation across time points and patient groups. Yet, cases showed biomarker concentrations suggestive of enhanced inflammation and a more disturbed endothelial barrier function, both at study enrollment (median 2 days after ICU admission) and in the path to pneumonia diagnosis (median 5 days after ICU admission). Baseline host response biomarker aberrations were most profound in patients who developed pneumonia either shortly (< 5 days, n = 105) or late (> 10 days, n = 68) after ICU admission.

Conclusions

Critically ill patients who develop an ICU-acquired pneumonia, compared with those who do not, display alterations in plasma protein biomarker concentrations indicative of stronger proinflammatory, procoagulant and (injurious) endothelial cell responses.

Trial registration: ClinicalTrials.gov Identifier: NCT02413242, posted April 9th, 2015.

Graphical abstract