bluuebunny/crossref_metadata_2025 huggingface dataset:
P53 Activation Promotes Maturational Characteristics of Pluripotent Stem Cell‐Derived Cardiomyocytes in 3‐Dimensional Suspension Culture Via FOXO‐FOXM1 Regulation
Authors: Velayutham Nivedhitha , Garbern Jessica C. , Elwell Hannah L. T. , Zhuo Zhu , Rüland Laura , Elcure Alvarez Farid , Frontini Sara , Rodriguez Carreras Yago , Eichholtz Marie , Ricci‐Blair Elisabeth , Shaw Jeanna Y. , Bouffard Aldric H. , Sokol Morgan , Mancheño Juncosa Estela , Rhoades Seth , van den Berg Daphne , Kreymerman Alexander , Aoyama Junya , Höfflin Jens , Ryan Herb , Ho Sui Shannan , Lee Richard T.
Published: June 2024

Background

Current protocols generate highly pure human induced pluripotent stem cell–derived cardiomyocytes (hiPSC‐CMs) in vitro that recapitulate characteristics of mature in vivo cardiomyocytes. Yet, a risk of arrhythmias exists when hiPSC‐CMs are injected into large animal models. Thus, understanding hiPSC‐CM maturational mechanisms is crucial for clinical translation. Forkhead box (FOX) transcription factors regulate postnatal cardiomyocyte maturation through a balance between FOXO and FOXM1. We also previously demonstrated that p53 activation enhances hiPSC‐CM maturation. Here, we investigate whether p53 activation modulates the FOXO/FOXM1 balance to promote hiPSC‐CM maturation in 3‐dimensional suspension culture.

Methods and Results

Three‐dimensional cultures of hiPSC‐CMs were treated with Nutlin‐3a (p53 activator, 10 μM), LOM612 (FOXO relocator, 5 μM), AS1842856 (FOXO inhibitor, 1 μM), or RCM‐1 (FOXM1 inhibitor, 1 μM), starting 2 days after onset of beating, with dimethyl sulfoxide (0.2% vehicle) as control. P53 activation promoted hiPSC‐CM metabolic and electrophysiological maturation alongside FOXO upregulation and FOXM1 downregulation, in n=3 to 6 per group for all assays. FOXO inhibition significantly decreased expression of cardiac‐specific markers such as TNNT2. In contrast, FOXO activation or FOXM1 inhibition promoted maturational characteristics such as increased contractility, oxygen consumption, and voltage peak maximum upstroke velocity, in n=3 to 6 per group for all assays. Further, by single‐cell RNA sequencing of n=2 LOM612‐treated cells compared with dimethyl sulfoxide, LOM612‐mediated FOXO activation promoted expression of cardiac maturational pathways.

Conclusions

We show that p53 activation promotes FOXO and suppresses FOXM1 during 3‐dimensional hiPSC‐CM maturation. These results expand our understanding of hiPSC‐CM maturational mechanisms in a clinically‐relevant 3‐dimensional culture system.
Small‐Vessel Disease and Intracranial Large Artery Disease in Brain MRI Predict Dementia and Acute Coronary Syndrome, Respectively: A Prospective, Observational Study in the Population at High Vascular Risk
Authors: Kitagawa Kazuo , Toi Sono , Hosoya Megumi , Yoshizawa Hiroshi
Published: June 2024

Background

We aimed to clarify the predictive value of cerebral small‐vessel disease and intracranial large artery disease (LAD) observed in magnetic resonance imaging of the brain and magnetic resonance angiography on future vascular events and cognitive impairment.

Methods and Results

Data were derived from a Japanese cohort with evidence of cerebral vessel disease on magnetic resonance imaging. This study included 862 participants who underwent magnetic resonance angiography after excluding patients with a modified Rankin Scale score >1 and Mini‐Mental State Examination score <24. We evaluated small‐vessel disease such as white matter hyperintensities and lacunes in magnetic resonance imaging and LAD with magnetic resonance angiography. Outcomes were incident stroke, dementia, acute coronary syndrome, and all‐cause death. Over a median follow‐up period of 4.5 years, 54 incident stroke, 39 cases of dementia, and 27 cases of acute coronary syndrome were documented. Both small‐vessel disease (white matter hyperintensities and lacunes) and LAD were associated with stroke; however, only white matter hyperintensities were related to dementia. In contrast, only LAD was associated with acute coronary syndrome. Among the 357 patients with no prior history of stroke, coronary or peripheral artery disease, or atrial fibrillation, white matter hyperintensities emerged as the sole predictor of future stroke and dementia, while LAD was the sole predictor of acute coronary syndrome.

Conclusions

Among cerebral vessels, small‐vessel disease could underlie the cognitive impairment while LAD was associated with coronary artery disease as atherosclerotic vessel disease.
Urinary Equol and Equol‐Predicting Microbial Species Are Favorably Associated With Cardiometabolic Risk Markers in Chinese Adults
Authors: Liang Shaoxian , Zhang Honghua , Mo Yufeng , Li Yamin , Zhang Xiaoyu , Cao Hongjuan , Xie Shaoyu , Wang Danni , Lv Yaning , Wu Yaqin , Zhang Zhuang , Yang Wanshui
Published: June 2024

Background

The association between soy isoflavones intake and cardiometabolic health remains inconclusive. We investigated the associations of urinary biomarkers of isoflavones including daidzein, glycitein, genistein, equol (a gut microbial metabolite of daidzein), and equol‐predicting microbial species with cardiometabolic risk markers.

Methods and Results

In a 1‐year study of 305 Chinese community‐dwelling adults aged ≥18 years, urinary isoflavones, fecal microbiota, blood pressure, blood glucose and lipids, and anthropometric data were measured twice, 1 year apart. Brachial‐ankle pulse wave velocity was also measured after 1 year. A linear mixed‐effects model was used to analyze repeated measurements. Logistic regression was used to calculate the adjusted odds ratio (aOR) and 95% CI for the associations for arterial stiffness. Each 1 μg/g creatinine increase in urinary equol concentrations was associated with 1.47%, 0.96%, and 3.32% decrease in triglycerides, plasma atherogenic index, and metabolic syndrome score, respectively (all
P
<0.05), and 0.61% increase in high‐density lipoprotein cholesterol (
P
=0.025). Urinary equol was also associated with lower risk of arterial stiffness (aOR, 0.28 [95% CI, 0.09–0.90];
P
trend
=0.036). We identified 21 bacterial genera whose relative abundance was positively associated with urinary equol (false discovery rate‐corrected
P
<0.05) and constructed a microbial species score to reflect the overall equol‐predicting capacity. This score (per 1‐point increase) was inversely associated with triglycerides (percentage difference=−1.48%), plasma atherogenic index (percentage difference=−0.85%), and the risk of arterial stiffness (aOR, 0.27 [95% CI, 0.08–0.88]; all
P
<0.05).

Conclusions

Our findings suggest that urinary equol and equol‐predicting microbial species may improve cardiometabolic risk parameters in Chinese adults.
Exercise Hemodynamics and Mitochondrial Oxidative Capacity in Disease Stages of Wild‐Type Transthyretin Amyloid Cardiomyopathy
Authors: Ladefoged Bertil , Pedersen Anders Dahl , Seefeldt Jacob , Nielsen Bent Roni Ranghøj , Eiskjær Hans , Lichscheidt Emil , Clemmensen Tor , Gillmore Julian David , Poulsen Steen Hvitfeldt
Published: June 2024

Background

Wild‐type transthyretin amyloid (ATTRwt) cardiomyopathy is increasingly recognized in the development of heart failure. The link between cardiac performance, hemodynamics, and mitochondrial function in disease stages of ATTRwt has not previously been studied but may provide new insights into the pathophysiology and clinical performance of the patients.

Methods and Results

The study investigated 47 patients diagnosed with ATTRwt at Aarhus University Hospital, Denmark. Patients were stratified according to the disease stages of the National Amyloidosis Centre (NAC) as NAC I with low levels of NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) (NAC I‐L, n=14), NAC I with high levels NT‐proBNP (NAC I‐H, n=20), and NAC II‐III (n=13). Exercise testing with simultaneous right heart catheterization was performed in all patients. Endomyocardial biopsies were collected from the patients and the mitochondrial oxidative phosphorylation capacity was assessed. All NAC disease groups, even in the NAC I‐L group, a significant abnormal increase in biventricular filling pressures were noted during exercise while the filling pressures was normal or near normal at rest. The inotropic response to exercise was reduced with diminished increase in cardiac output which was significantly more pronounced in the NAC I‐H (Diff. ‐2.4, 95% CI (−4.2: −0.7),
P
=0.00) and the NAC II‐III group (Diff: −3.1 L/min, 95% CI (−5.2: −1.1),
P
=0.00) compared with the NAC I‐L group. The pulmonary artery wedge pressure to cardiac output ratio at peak exercise was significantly different between NAC I‐L and NAC II‐III (Diff: 1.6 mm Hg*min/L, 95% CI (0.01:3.3,
P
=0.04)). Patients with ATTRwt had a reduced oxidative phosphorylation capacity which correlated to left ventricular mass but not to cardiac output capacity.

Conclusions

An abnormal restrictive left ventricle and right ventricle response to exercise was demonstrated, even present in patients with early‐stage ATTRwt. In more advanced disease stages a progressive impairment of the pressure‐flow relationship was noted. The myocyte energetics is deranged but not associated to the contractile reserve or restrictive filling characteristics in ATTRwt.
Remote Forcing for a Circulation Pattern Favorable to Surface Melt over the Ross Ice Shelf
Authors: Fang Yingfei , Yang Song , Hu Xiaoming , Lin Shuheng , Screen James A. , Chen Shangfeng
Published: June 2024

The Ross Ice Shelf (RIS) experiences surface melt events in summer, which could accelerate ice loss and destabilize the ice sheet in a warming world. This study links the interannual variability of RIS surface melt to the northerly wind anomaly over the Ross Sea sector, which is established in association with the quasigeostrophic barotropic Rossby wave trains from the tropical Pacific and subtropical Australia toward West Antarctica. Atmospheric general circulation model experiments suggest that these Rossby wave trains are regulated by El Niño–related sea surface temperature (SST) anomalies in the tropical central–eastern Pacific and atmospheric heating anomalies over western Australia. El Niño provides an important forcing of the atmospheric circulation anomalies over the Ross Sea via inducing a Rossby wave train, and most surface melt events over the RIS happen during El Niño years. In addition, the anomalous atmospheric heating over western Australia, which is independent of El Niño, is another important forcing that triggers a Rossby wave train extending from subtropical Australia to the Ross Sea. The northerly flow toward the Ross Sea induces strong poleward moisture and heat transport, which further contributes to surface melt over the RIS.

Significance Statement

During austral summer, surface melt occurs over the Ross Ice Shelf, accelerates ice loss, and poses ice-sheet destabilization risks in a warming world. The northerly wind anomaly over the Ross sector provides strong poleward heat and moisture transport and is favorable for the surface melt. This wind anomaly is influenced by two remote forcings, El Niño and heating anomaly over western Australia, through generating Rossby wave trains from the tropics and subtropical Australia. This study reveals a previously unexplored relationship that atmospheric heating over western Australia influences large-scale circulation, contributing to surface melt.
Circular Asymmetry of Ocean Mesoscale Eddy
Authors: Lin Yanjiang , Wang Guihua
Published: June 2024

In the global ocean, mesoscale eddies frequently deviate from a circular shape [circular asymmetry (CA)]. On average, anticyclonic eddies display slightly larger asymmetry than that of cyclonic eddies. Both types of eddies exhibit larger asymmetry during the periods of generation and extinction and smaller asymmetry during the intermediate periods. CA’s spatial distribution is dominantly controlled by the eddy’s rotational speed, radius, meridional displacement, and the background oceanic circulation. A decrease in rotational speed, an increase in radius, moving poleward (toward the equator), and/or moving into regions with smaller (larger) mean dynamic topography can enhance the asymmetry of anticyclonic (cyclonic) eddies. A weak advective nonlinearity of the eddy, represented by the ratio of the eddy’s rotational speed to its translation speed, also helps to enhance the asymmetry. Eddy with an asymmetric structure may be important for marine mixing processes.

Significance Statement

Mesoscale eddies are often assumed to be circular and symmetric. However, global observations reveal that eddies frequently diverge from a circular shape, displaying circular asymmetry (CA). The asymmetric structure of eddy is poorly investigated in the global ocean, especially in regions close to the strong oceanic currents. This study reported the evolution of eddy’s asymmetric structure and its spatial distribution. Statistical results show that CA is dominantly controlled by the eddy’s rotational speed, radius, meridional displacement, and the background oceanic circulation. This study provides a new perspective on the evolution of eddy’s structure and may be important in oceanic mixing.
The effect of expiratory flow limitation on supine persistent hyperinflation in COPD: a prospective observational study
Authors: Srinivasan Meera , Pollard Hannah , Chapman David G. , Tonga Katrina , Patel Kieran , Blokland Kaj , Touma David , Thamrin Cindy , Cross Troy , Prisk Kim , King Gregory G.
Published: June 2024

Introduction

COPD is characterised by airflow obstruction, expiratory airway collapse and closure causing expiratory flow limitation (EFL) and hyperinflation. Supine posture may worsen ventilatory function in COPD, which may cause hyperinflation to persist and contribute to symptoms of orthopnoea and sleep disturbance. Our aim was to determine the impact of supine posture on hyperinflation, dynamic elastance and EFL in COPD and healthy subjects. We hypothesised that changes in hyperinflation in supine posture are influenced by EFL and gas trapping in COPD.

Methods

Clinically stable COPD patients (compatible symptoms, smoking >10 pack-years, obstructed spirometry) and healthy controls underwent oscillometry in the seated and supine positions. Hyperinflation was measured by inspiratory capacity (IC) and the ratio of IC to total lung capacity (IC/TLC) while seated and supine EFL was measured as the difference in mean inspiratory and mean expiratory oscillatory reactance at 5 Hz (Xrs5). Relationships between IC, IC/TLC andXrs5, were examined by Spearman correlation.

Results

42 COPD patients demonstrated no change in IC/TLC from seated (0.31 L) to supine (0.32 L) position (p=0.079) compared to significant increases seen in 14 control subjects (0.37 L seatedversus0.44 L supine; p<0.001). In COPD, worse dynamic elastance (Xrs5rs0.499; p=0.001) and EFL (ΔXrs5rs−0.413; p=0.007), along with increased age and lower body-mass-index were predictors of supine hyperinflation.

Conclusion

Supine persistent hyperinflation occurs in COPD and is associated with increased dynamic elastance and EFL, likely the result of increased airway closure due to gravitational redistribution of lung mass.
How to distinguish PPI-refractory from PPI-responsive patients in gastro-oesophageal reflux-induced chronic cough: post-reflux swallow induced peristaltic wave index and mean nocturnal baseline impedance provide new predictive factors
Authors: Li Wanzhen , Sha Bingxian , Bai Haodong , Zhang Tongyangzi , Wang Shengyuan , Ambedkar Kumar Yadav , Zhu Yiqing , Yu Li , Xu Xianghuai
Published: June 2024

Background

The results of empirical trials with proton pump inhibitors (PPIs) for management of gastro-oesophageal reflux-induced chronic cough (GERC) have resulted in considerable controversy, and the mechanism of PPI refractoriness remains unclear. Our study aims to identify the predictors of PPI refractoriness of GERC in a retrospective clinical study.

Methods

In total, 128 GERC patients were enrolled between March 2018 and October 2022. Regression analysis was utilised to create a model for predicting PPI-refractory of GERC using retrospective analysis of the general data and MII-pH indicators.

Results

The post-reflux swallow induced peristaltic wave index (PSPWI) was lower in the PPI-refractory group than the PPI-responsive group (33.89±7.38versus39.45±9.47, respectively, p<0.001), as were the mean nocturnal baseline impedance (MNBI) and proximal MNBI (2092.11 (IQR: 652.23)]versus2426.52 (IQR: 917.39) Ω, respectively, p=0.012; 1599.50 (IQR: 1206.63)versus2274.50 (IQR: 1775.29) Ω, respectively, p=0.001). Multivariate logistic regression analysis identified the PSPWI (odds ratio 0.919, p=0.001) as an independent predictor of PPI-refractory GERC.

Conclusions

The diagnostic value of both proximal MNBI ≤39.90% and MNBI ≤2233.58 Ω had moderate sensitivity (71.67%) and specificity (75.00%) to identify PPI-refractory GERC.
Assessing automated air-taxis for urban mobility
Authors: Hu Bin , Brandstätter Georg , Müller Johannes , Stern Patrick , Schaffenberger Alexander , Fallast Arno , Lesak Samuel , Meinhard Dieter
Published: June 2024

This paper explores the feasibility and potential implications of automated air-taxis as a new mode of urban transport. By applying flight simulation and operations research, we investigate different questions regarding travel time, travel costs, and transport sustainability. As practical application, we consider the transportation service between the city and the airport, as well as on-demand air-taxi services within the city of Vienna. We compare the air-taxis with gasoline taxis and e-taxis, as they serve analogous transportation needs and cater to a similar clientele. In our effort to assess the feasibility of air-taxis, we aim to answer crucial questions that will influence the future of urban transportation. Our study examines how efficient air-taxis are in reducing travel time and explores their cost dynamics, addressing the affordability for passengers and their value of travel time savings. Additionally, we investigate their environmental impact by looking into energy consumption and CO2 emissions. Through a rigorous analysis of empirical data and simulation outcomes, we aim to provide a comprehensive perspective that informs policy decisions and guides the evolution of urban transportation networks in the years to come.
Does female control and male mating system predict courtship investment and mating outcomes? A comparative study in five widow spider species (genus Latrodectus) tested under similar laboratory conditions
Authors: Baruffaldi Luciana , Andrade Maydianne C. B.
Published: June 2024

Background

Male courtship investment may evolve in response to the male’s expectation of future mating opportunities or the degree of female control during mating interactions. We used a comparative approach to test this hypotheses by assessing the courtship and mating behaviors of five widow spider species (genus Latrodectus) under common laboratory conditions. We predicted male investment in courtship would be higher in species where males mate only once because of high cannibalism rates (monogyny, L. geometricus, L. hasselti, L. mirabilis), compared to species with rare cannibalism (L. mactans, L. hesperus) in which males should reserve energy for future mating opportunities. Increased male investment, measured as courtship duration, might also evolve with increased female control over mating outcomes if females prefer longer courtships. We tested this by assessing the frequency of copulations, timing of sexual cannibalism, and the degree of female-biased size dimorphism, which is expected to be negatively correlated with the energetic cost of rebuffing male mating attempts.

Results

Copulation frequency was consistently lower in species with extreme female-skewed size dimorphism, and where sexual cannibalism was more prevalent, suggesting the importance of female control for mating outcomes. We confirmed significant interspecific variation in average courtship duration, but contrary to predictions, it was not predicted by male mating system, and there was no consistent link between courtship duration and sexual size dimorphism.

Conclusion

We show that the degree of sexual dimorphism is not only correlated with sexual cannibalism, but also with mating success since restriction of male copulation frequency by female Latrodectus affects paternity. However, predictions about male mating system or female control affecting courtship duration were not supported. We propose that the form of female control over mating and cannibalism, and male responses, might be more informative for understanding the evolution of courtship duration. For example, male tactics to avoid female aggression may drive lower courtship duration in species like L. mirabilis. Nonetheless, our results differ from inferences based on published studies of each species in isolation, illuminating the need for standardized data collection for behavioural comparative studies.
The co-occurrence of sarcoidosis and anti-PLA2R-associated membranous nephropathy in a patient with underlying genetic susceptibility
Authors: Ding Ying , Yao Yao , Wan Li , Qu Zhen , Yu Feng
Published: June 2024

Background

Sarcoidosis is a multisystemic inflammatory disease, characterized by the presence of non-caseating, epithelioid granulomas. Glomerular disease in patients with sarcoidosis is rare and membranous nephropathy (MN) is cited as the most common. The association between the two diseases remained unclear. This article reported a case of co-occurrence of sarcoidosis and anti-PLA2R-associated MN, to provide a possible relationship between these two entities.

Case presentation

A 61-year-old Chinese Han woman with a history of sarcoidosis was admitted to our hospital for nephrotic syndrome. Her sarcoidosis was diagnosed according to the adenopathy observed on the computed tomography scan and the biopsy of lymph nodes. The MN presented with nephrotic syndrome with a PLA2R antibody titer of 357RU/ml, and the final diagnosis was based on a renal biopsy. The patient’s sarcoidosis was remitted after treatment with prednisone. One year later MN was diagnosed, and she was treated with prednisone combined with calcineurin inhibitors, based on a full dose of renin-angiotensin system (RAS) inhibitor. The patient’s sarcoidosis had been in remission while the MN was recurrent, and her renal function deteriorated to end-stage renal disease 6 years later due to discontinuation of immunosuppression. A genetic test led to the identification of the HLA-DRB1*0301 and HLA-DRB1*150 genes associated with both sarcoidosis and MN, which provides a new possible explanation of the co-occurrence of these two diseases.

Conclusion

This case suggested for the first time a potential genetic connection between idiopathic MN and sarcoidosis which needs further studies in the future.
A systematic review and narrative synthesis of health literacy interventions among Spanish speaking populations in the United States
Authors: Hernandez Joel , Demiranda Liliana , Perisetla Priyanka , Andrews Lauren , Zhang Keer , Henderson Rebecca , Mittal Ajay , Norton Hannah F. , Hagen Melanie G.
Published: June 2024

Background

While many populations struggle with health literacy, those who speak Spanish preferentially or exclusively, including Hispanic, immigrant, or migrant populations, may face particular barriers, as they navigate a predominantly English-language healthcare system. This population also faces greater morbidity and mortality from treatable chronic diseases, such as hypertension and diabetes. The aim of this systematic review was to describe existing health literacy interventions for patients with a Spanish-language preference and present their effectiveness.

Methods

We carried out a systematic review where Web of Science, EMBASE, and PubMed were queried using MeSH terms to identify relevant literature. Included articles described patients with a Spanish-language preference participating in interventions to improve health literacy levels in the United States. Screening and data abstraction were conducted independently and in pairs. Risk of bias assessments were conducted using validated appraisal tools.

Results

A total of 2823 studies were identified, of which 62 met our eligibility criteria. The studies took place in a variety of community and clinical settings and used varied tools for measuring health literacy. Of the interventions, 28 consisted of in-person education and 27 implemented multimedia education, with 89% of studies in each category finding significant results. The remaining seven studies featured multimodal interventions, all of which achieved significant results.

Conclusion

Successful strategies included the addition of liaison roles, such as promotores (Hispanic community health workers), and the use of multimedia fotonovelas (photo comics) with linguistic and cultural adaptations. In some cases, the external validity of the results was limited. Improving low health literacy in patients with a Spanish-language preference, a population with existing barriers to high quality of care, may help them better navigate health infrastructure and make informed decisions regarding their health.

Registration

PROSPERO (available at https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021257655.t).
Unraveling the controversy between fasting and nonfasting lipid testing in a normal population: a systematic review and meta-analysis of 244,665 participants
Authors: Zaid Ahmed B. , Awad Samah M. , El-Abd Mona G , Saied Sara A. , Almahdy Shimaa K. , Saied AbdulRahman A , Elmalawany Alshimaa M. , AboShabaan Hind S. , Saleh Helmy S.
Published: June 2024

Background

The final decision to fast or not fast for routine lipid profile examination in a standard, healthy population is unclear. Whereas the United States and European protocols state that fasting for regular lipid analysis is unnecessary, the North American and Chinese guidelines still recommend fasting before routine lipid testing.

Aim

This study aimed to unravel the contradiction between the different protocols of lipid profile testing worldwide and clarify the effect of diet on lipid profile testing only in a regular, healthy population.

Methods

A literature search was conducted through May 2024. The analyses included studies performed from the date 2000 until now because the contradiction of guidelines for lipid profile testing appeared for the first time in this period. A planned internal validity evaluation was performed using the National Institute of Health (NIH) quality measurement tools for observational cohort, case‒control, controlled interventional, and cross-sectional studies. The data were synthesized according to RevMan 5.3.

Results

Eight studies with a total of 244,665 participants were included. The standardized mean difference in cholesterol in six studies showed significant differences in overall effect among fasting and nonfasting states (P < 0.00001), as did high-density lipoprotein cholesterol (P < 0.00001). At the same time, with respect to triglycerides and low-density lipoprotein cholesterol, there were notable variations in the overall effect between the fasted and nonfasted states (P < 0.00001 and P ≤ 0.001, respectively).

Conclusions

This meta-analysis concluded that fasting for lipid profile testing is preferred as a conservative model to reduce variability and increase consistency in patients’ metabolic status when sampling for lipid testing.
Association between triglyceride glucose index-related indices with gallstone disease among US adults
Authors: Fu Chang , Li Xiaocong , Wang Yongxin , Chen Junhong , Yang Yibo , Liu Kai
Published: June 2024

Background

Triglyceride glucose (TyG) index combined with obesity-related indicators [triglyceride glucose-body mass index (TyG-BMI), triglyceride glucose-waist to height ratio (TyG-WHtR), triglyceride glucose-waist circumference (TyG-WC)], represents emerging methodologies for assessing insulin resistance. The objective of this investigation was to explore the correlation between TyG-related indices and gallstone disease.

Methods

The study included 3740 adults from the 2017–2020 period of the National Health and Nutrition Examination Survey. TyG-BMI, TyG-WC, and TyG-WHtR were integrated as both continuous and categorical variables within the multivariate logistic model, respectively to evaluate the connection between various TyG-related indices and gallstone disease. Additionally, restriction cubic splines and subgroup analysis were employed to deepen our understanding of this relationship.

Results

When analyzed as continuous variables, positive correlations were observed between TyG-BMI, TyG-WC, TyG-WHtR and gallstone disease. The OR(95%CI) were 1.063(1.045,1.082) for TyG-BMI (per 10-unit), 1.026(1.018,1.034) for TyG-WC (per 10-unit) and 1.483(1.314,1.676) for TyG-WHtR (per 1-unit), respectively. When categorized into quartiles, these three TyG-related indices still show statistically significant associations with gallstone disease. Descending in order, the diagnostic capability for gallstone disease is demonstrated as follows: TyG-WHtR (AUC = 0.667), TyG-BMI (AUC = 0.647), and TyG-WC (AUC = 0.640).

Conclusion

There were significantly positive associations between TyG-related indices, including TyG-BMI, TyG-WC, and TyG-WHtR, and gallstone disease. Of these indices, TyG-WHtR demonstrated the most favorable performance in identifying the risk of gallstone disease.
Centenarians, semi and supercentenarians, COVID-19 and Spanish flu: a serological assessment to gain insight into the resilience of older centenarians to COVID-19
Authors: Trombetta Claudia Maria , Accardi Giulia , Aiello Anna , Calabrò Anna , Caruso Calogero , Ligotti Mattia Emanuela , Marchi Serena , Montomoli Emanuele , Neto Martin Mayora , Temperton Nigel , Candore Giuseppina
Published: June 2024

Background

Although it is well known that the older people have been the most susceptible to COVID-19, there are conflicting data on the susceptibility of centenarians. Two epidemiological study have shown that older centenarians (> 101 years old at the time of the 2020 pandemic peak) are more resilient than the remaining centenarians, suggesting that this resilience might be linked to the 1918 Spanish Flu pandemic. To gain insight into this matter, specifically whether the resilience of older centenarians to SARS-CoV-2 infection is linked to the Spanish Flu they had been affected by, we conducted a retrospective serological study. This study examined serum samples from 33 centenarians, encompassing semi- (aged > 104 < 110 years, N = 7) and supercentenarians (aged > 109 years, N = 4), born between 1905 and 1922, against both SARS-CoV-2 and 1918 H1N1 pseudotype virus.

Results

Anamnestic and laboratory data suggest that SARS-CoV-2 infection occurred in 8 centenarians. The infection appeared to have been asymptomatic or mild, and hospitalization was not required, despite 3 out of 8 being between 109 and 110 years old. The levels of anti-spike antibodies in centenarians infected and/or vaccinated were higher, although not significantly, than those produced by a random sample of seventy-year-old individuals used as controls. All centenarians had antibody levels against the 1918 H1N1 virus significantly higher (almost 50 times) than those observed in the quoted group of seventy-year-old subjects, confirming the key role in maintaining immunological memory from a priming that occurred over 100 years ago. Centenarians whose blood was collected prior to the pandemic outbreak demonstrated neutralising antibodies against the 1918 H1N1 virus, but all these subjects tested negative for SARS-CoV-2.

Conclusion

This retrospective study shows that older centenarians are quite resilient to COVID-19, as they are capable of producing good levels of neutralising antibodies and experiencing mild or asymptomatic disease. This could be attributed to the 1918 Spanish flu pandemic through mechanisms other than the presence of cross-reactive antibodies between the 1918 H1N1 virus and SARS-CoV-2. Another possibility is that the association is purely temporal, solely correlated with the advanced age of resilient centenarians compared to those born after 1918, since older centenarians are known to have better control of immune-inflammatory responses.
Evaluation of Parasight All-in-One system for the automated enumeration of helminth ova in canine and feline feces
Authors: Castle Timothy Graham , Britton Leah , Ripley Britt , Ubelhor Elizabeth , Slusarewicz Paul
Published: June 2024

Background

 Digital imaging combined with deep-learning-based computational image analysis is a growing area in medical diagnostics, including parasitology, where a number of automated analytical devices have been developed and are available for use in clinical practice.

Methods

The performance of Parasight All-in-One (AIO), a second-generation device, was evaluated by comparing it to a well-accepted research method (mini-FLOTAC) and to another commercially available test (Imagyst). Fifty-nine canine and feline infected fecal specimens were quantitatively analyzed by all three methods. Since some samples were positive for more than one parasite, the dataset consisted of 48 specimens positive for Ancylostoma spp., 13 for Toxocara spp. and 23 for Trichuris spp.

Results

The magnitude of Parasight AIO counts correlated well with those of mini-FLOTAC but not with those of Imagyst. Parasight AIO counted approximately 3.5-fold more ova of Ancylostoma spp. and Trichuris spp. and 4.6-fold more ova of Toxocara spp. than the mini-FLOTAC, and counted 27.9-, 17.1- and 10.2-fold more of these same ova than Imagyst, respectively. These differences translated into differences between the test sensitivities at low egg count levels (< 50 eggs/g), with Parasight AIO > mini-FLOTAC > Imagyst. At higher egg counts Parasight AIO and mini-FLOTAC performed with comparable precision (which was significantly higher that than Imagyst), whereas at lower counts (> 30 eggs/g) Parasight was more precise than both mini-FLOTAC and Imagyst, while the latter two methods did not significantly differ from each other.

Conclusions

In general, Parasight AIO analyses were both more precise and sensitive than mini-FLOTAC and Imagyst and quantitatively correlated well with mini-FLOTAC. While Parasight AIO produced lower raw counts in eggs-per-gram than mini-FLOTAC, these could be corrected using the data generated from these correlations.

Graphical Abstract
A geospatial analysis of local intermediate snail host distributions provides insight into schistosomiasis risk within under-sampled areas of southern Lake Malawi
Authors: Reed Amber L. , Al-Harbi Mohammad H. , Makaula Peter , Condemine Charlotte , Hesketh Josie , Archer John , Jones Sam , Kayuni Sekeleghe A. , Musaya Janelisa , Stanton Michelle C. , Stothard J. Russell , Fronterre Claudio , Jewell Christopher
Published: June 2024

Background

Along the southern shoreline of Lake Malawi, the incidence of schistosomiasis is increasing with snails of the genera Bulinus and Biomphalaria transmitting urogenital and intestinal schistosomiasis, respectively. Since the underlying distribution of snails is partially known, often being focal, developing pragmatic spatial models that interpolate snail information across under-sampled regions is required to understand and assess current and future risk of schistosomiasis.

Methods

A secondary geospatial analysis of recently collected malacological and environmental survey data was undertaken. Using a Bayesian Poisson latent Gaussian process model, abundance data were fitted for Bulinus and Biomphalaria. Interpolating the abundance of snails along the shoreline (given their relative distance along the shoreline) was achieved by smoothing, using extracted environmental rainfall, land surface temperature (LST), evapotranspiration, normalised difference vegetation index (NDVI) and soil type covariate data for all predicted locations. Our adopted model used a combination of two-dimensional (2D) and one dimensional (1D) mapping.

Results

A significant association between normalised difference vegetation index (NDVI) and abundance of Bulinus spp. was detected (log risk ratio − 0.83, 95% CrI − 1.57, − 0.09). A qualitatively similar association was found between NDVI and Biomphalaria sp. but was not statistically significant (log risk ratio − 1.42, 95% CrI − 3.09, 0.10). Analyses of all other environmental data were considered non-significant.

Conclusions

The spatial range in which interpolation of snail distributions is possible appears < 10km owing to fine-scale biotic and abiotic heterogeneities. The forthcoming challenge is to refine geospatial sampling frameworks with future opportunities to map schistosomiasis within actual or predicted snail distributions. In so doing, this would better reveal local environmental transmission possibilities.

Graphical Abstract
Fully automated assessment of the future liver remnant in a blood-free setting via CT before major hepatectomy via deep learning
Authors: Xie Tingting , Zhou Jingyu , Zhang Xiaodong , Zhang Yaofeng , Wang Xiaoying , Li Yongbin , Cheng Guanxun
Published: June 2024

Objectives

To develop and validate a deep learning (DL) model for automated segmentation of hepatic and portal veins, and apply the model in blood-free future liver remnant (FLR) assessments via CT before major hepatectomy.

Methods

3-dimensional 3D U-Net models were developed for the automatic segmentation of hepatic veins and portal veins on contrast-enhanced CT images. A total of 170 patients treated from January 2018 to March 2019 were included. 3D U-Net models were trained and tested under various liver conditions. The Dice similarity coefficient (DSC) and volumetric similarity (VS) were used to evaluate the segmentation accuracy. The use of quantitative volumetry for evaluating resection was compared between blood-filled and blood-free settings and between manual and automated segmentation.

Results

The DSC values in the test dataset for hepatic veins and portal veins were 0.66 ± 0.08 (95% CI: (0.65, 0.68)) and 0.67 ± 0.07 (95% CI: (0.66, 0.69)), the VS values were 0.80 ± 0.10 (95% CI: (0.79, 0.84)) and 0.74 ± 0.08 (95% CI: (0.73, 0.76)), respectively No significant differences in FLR, FLR% assessments, or the percentage of major hepatectomy patients were noted between the blood-filled and blood-free settings (p = 0.67, 0.59 and 0.99 for manual methods, p = 0.66, 0.99 and 0.99 for automated methods, respectively) according to the use of manual and automated segmentation methods.

Conclusion

Fully automated segmentation of hepatic veins and portal veins and FLR assessment via blood-free CT before major hepatectomy are accurate and applicable in clinical cases involving the use of DL.

Critical relevance statement

Our fully automatic models could segment hepatic veins, portal veins, and future liver remnant in blood-free setting on CT images before major hepatectomy with reliable outcomes.

Key Points

Fully automatic segmentation of hepatic veins and portal veins was feasible in clinical practice.

Fully automatic volumetry of future liver remnant (FLR)% in a blood-free setting was robust.

No significant differences in FLR% assessments were noted between the blood-filled and blood-free settings.

Graphical Abstract
A systematic review of validity of US survey measures for assessing substance use and substance use disorders
Authors: Tang Yuni , Caswell Erin , Mohamed Rowida , Wilson Natalie , Osmanovic Edis , Smith Gordon , Hartley Summer D. , Bhandari Ruchi
Published: June 2024

Background

The steep rise in substance use and substance use disorder (SUD) shows an urgency to assess its prevalence using valid measures. This systematic review summarizes the validity of measures to assess the prevalence of substance use and SUD in the US estimated in population and sub-population-based surveys.

Methods

A literature search was performed using nine online databases. Studies were included in the review if they were published in English and tested the validity of substance use and SUD measures among US adults at the general or sub-population level. Independent reviews were conducted by the authors to complete data synthesis and assess the risk of bias.

Results

Overall, 46 studies validating substance use/SUD (n = 46) measures were included in this review, in which 63% were conducted in clinical settings and 89% assessed the validity of SUD measures. Among the studies that assessed SUD screening measures, 78% examined a generic SUD measure, and the rest screened for specific disorders. Almost every study used a different survey measure. Overall, sensitivity and specificity tests were conducted in over a third of the studies for validation, and 10 studies used receiver operating characteristics curve.

Conclusion

Findings suggest a lack of standardized methods in surveys measuring and reporting prevalence of substance use/SUD among US adults. It highlights a critical need to develop short measures for assessing SUD that do not require lengthy, time-consuming data collection that would be difficult to incorporate into population-based surveys assessing a multitude of health dimensions.

Systematic review registration

PROSPERO CRD42022298280.
Approximation properties by shifted knots type of α-Bernstein–Kantorovich–Stancu operators
Authors: Nasiruzzaman Md. , Dilshad Mohammad , Albalawi Bader Mufadhi Eid , Ajmal Mohammad Rehan
Published: June 2024

Through the real polynomials of the shifted knots, the α-Bernstein–Kantorovich operators are studied in their Stancu form, and the approximation properties are obtained. We obtain some direct approximation theorem in terms of Lipschitz type maximum function and Peetre’s K-functional, as well as Korovkin’s theorem. Eventually, the modulus of continuity is used to compute the upper bound error estimation.
Data-Driven Insights into Controlling the Reactivity of Supplementary Cementitious Materials in Hydrated Cement
Authors: Degefa Aron Berhanu , Jeon Geonyeol , Choi Sooyung , Bak JinYeong , Park Seunghee , Yoon Hyungchul , Park Solmoi
Published: June 2024

Supplementary cementitious materials (SCMs) play an essential role in sustainable construction due to their potential to reduce carbon emissions, promote circular economy principles, and enhance the properties of concrete. However, the inherent diversity of SCMs makes it challenging to predict their degree of reaction (DOR). This study applies machine learning techniques to predict DOR while exploring key parameters affecting it. Five machine learning models are utilized: linear regression, Gaussian process regression (GPR), decision tree regression, support vector machine and extreme gradient boosting, with GPR providing the most accurate and adaptable prediction. The study delves into the impact of various parameters on DOR, revealing their significance. Silica content emerges as the most critical, followed by particle size distribution, specific gravity, and water-to-cement (W/C) ratio. Optimizing DOR requires extending curing time, reducing particle size distribution, and considering optimal silica content and W/C ratio. This research emphasizes the importance of understanding the relationships between parameters and the DOR of SCMs, providing insights to enhance the efficiency of SCMs in cementitious systems through machine learning and data-driven analysis.
Rapid jail-based implementation of overdose education and naloxone distribution in response to the COVID-19 pandemic
Authors: Oser Carrie B. , McGladrey Margaret , Booty Marisa , Surratt Hilary , Knudsen Hannah K. , Freeman Patricia R. , Stevens-Watkins Danelle , Roberts Monica F. , Staton Michele , Young April , Draper Emma , Walsh Sharon L.
Published: June 2024

Background

People incarcerated in jails are highly impacted by the opioid epidemic, and overdose education and naloxone distribution (OEND) is an effective strategy to reduce opioid overdose deaths. This study examines barriers and facilitators of fast-track OEND implementation within the jails in the Wave 1 Kentucky counties of the HEALing Communities Study during the COVID-19 pandemic.

Methods

Meeting minutes with jail stakeholders were qualitatively coded using the Practical, Robust Implementation and Sustainability Model (PRISM) as the coding framework. The analysis highlighted the top barriers and facilitators to fast-track OEND implementation within the PRISM framework.

Results

Space and staffing shortages related to the COVID-19 pandemic, disruptions in interorganizational programming from pandemic-related service suspensions, and a lack of technological solutions (e.g., reliable Internet access) for socially distanced delivery were the top barriers to fast-track OEND implementation. In addition, there were limitations on non-jail staff access to jails during COVID-19. Top facilitators included jail leadership support, the option to prioritize high-risk groups, and the incorporation of OEND processes into existing communications and management software. While the COVID-19 pandemic strained jail infrastructure, jail and partner agency collaboration led to creative implementation strategies for the successful integration of OEND into jail operations. Urban jails were more likely than rural jails to be early adopters of OEND during the public health emergency.

Conclusions

Understanding the barriers to and facilitators of OEND within jails will improve implementation efforts seeking to curb opioid overdose deaths. Jail leadership support and interorganizational efforts were key facilitators to implementation; therefore, it is recommended to increase buy-in with multiple agencies to promote success. Challenges brought on by COVID-19 have resulted in a need for innovative solutions for implementation.

Clinical trial information

ClinicalTrials.gov, NCT04111939, Submitted 30 September 2019, https://clinicaltrials.gov/study/NCT04111939?titles=HEALing%20Communities%20Study&rank=1.
PUB40 attenuates Phytophthora capsici resistance by destabilizing the MEK2-SIPK/WIPK cascade in Nicotiana benthamiana
Authors: Zhang Yifan , Wang Jinghao , Pi Lei , Wang Nan , Peng Hao , Xu Guangyuan , Yin Zhiyuan , Dou Daolong
Published: June 2024

The mitogen-activated protein kinase (MAPK) cascade MEK2-SIPK/WIPK is essential for immunity in Solanaceae plants. This cascade is tightly controlled to prevent harmful hyperactivation. However, the E3 ubiquitin ligases utilized by plants to reduce MEK2- SIPK/WIPK protein levels remain largely elusive. Here, we confirmed the essential role of Nicotiana benthamiana MEK2-SIPK/WIPK in resistance to the oomycete pathogen Phytophthora capsici. Using tobacco rattle virus (TRV)-based gene silencing, we screened prevalent plant U-box protein (PUB)-type E3 ligases with Armadillo (ARM) repeats to characterize those involved in Phytophthora resistance and MEK2-SIPK/WIPK degradation. We found that pub40 knockdown mutants exhibited significantly enhanced resistance to P. capsici. NbPUB40 was under ubiquitination and proteasomal degradation in planta, with two conserved sites (Cys28 and Val41) in the U-box domain being essential for its activity. NbPUB40 was shown to interact with the whole MEK2-SIPK/WIPK cascade and promote their degradation, the ubiquitination levels of which were also notably reduced in the pub40 mutant. Our results reveal a mechanism in which a PUB E3 ubiquitin ligase negatively regulates plant P. capsici resistance by destabilizing the MEK2-SIPK/WIPK cascade.