bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

AbstractBackgroundDiabetes 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.MethodsThis 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.ResultsThe 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.ConclusionsThe 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

AbstractBackgroundSedentary 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.MethodsWe 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.ResultsDuring 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).ConclusionsHigher 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

Abstract
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

AbstractBackgroundThe 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.MethodsThe 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.ResultsIn 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.ConclusionsThe 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

Abstract
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

Abstract
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
Computational physiological models for individualised mechanical ventilation: a systematic literature review focussing on quality, availability, and clinical readiness
Authors: Warnaar R. S. P. , Mulder M. P. , Fresiello L. , Cornet A. D. , Heunks L. M. A. , Donker D. W. , Oppersma E. 
Published: July 2023

Abstract
Background
Individualised optimisation of mechanical ventilation (MV) remains cumbersome in modern intensive care medicine. Computerised, model-based support systems could help in tailoring MV settings to the complex interactions between MV and the individual patient's pathophysiology. Therefore, we critically appraised the current literature on computational physiological models (CPMs) for individualised MV in the ICU with a focus on quality, availability, and clinical readiness.

Methods
A systematic literature search was conducted on 13 February 2023 in MEDLINE ALL, Embase, Scopus and Web of Science to identify original research articles describing CPMs for individualised MV in the ICU. The modelled physiological phenomena, clinical applications, and level of readiness were extracted. The quality of model design reporting and validation was assessed based on American Society of Mechanical Engineers (ASME) standards.

Results
Out of 6,333 unique publications, 149 publications were included. CPMs emerged since the 1970s with increasing levels of readiness. A total of 131 articles (88%) modelled lung mechanics, mainly for lung-protective ventilation. Gas exchange (n = 38, 26%) and gas homeostasis (n = 36, 24%) models had mainly applications in controlling oxygenation and ventilation. Respiratory muscle function models for diaphragm-protective ventilation emerged recently (n = 3, 2%). Three randomised controlled trials were initiated, applying the Beacon and CURE Soft models for gas exchange and PEEP optimisation. Overall, model design and quality were reported unsatisfactory in 93% and 21% of the articles, respectively.

Conclusion
CPMs are advancing towards clinical application as an explainable tool to optimise individualised MV. To promote clinical application, dedicated standards for quality assessment and model reporting are essential.
Trial registration number PROSPERO—CRD42022301715. Registered 05 February, 2022.