bluuebunny/crossref_metadata_2025 huggingface dataset:
High-normal systolic blood pressure in early midlife is a stronger risk factor for incident hypertension later in life for women than men
Authors: Ohldieck A E , Kringeland E K , Midtboe H B M , Gerdts E G
Published: November 2023

Background

We have previously found that having high-normal blood pressure (BP) in early midlife is a stronger risk factor for incident hypertension later in life for women than for men. Whether this risk is related both to high-normal systolic and diastolic BP is not known.

Purpose

To explore whether there is a sex difference in risk of incident hypertension related to high-normal systolic and diastolic BP in early midlife.

Methods

In the community-based Hordaland Health Study, 1025 women and 703 men were examined at age 42 years (baseline) and re-examined after 26 years. Patients with hypertension at baseline were excluded. Attended BP was measured in triplets, and clinic BP taken as the average of the two last measurements. High-normal systolic BP was identified as systolic BP of 130-139 mmHg and high normal diastolic BP as diastolic BP 85-89 mmHg. Incident hypertension was identified as BP ≥140/90 mmHg or patient reported use of antihypertensive drugs on the follow-up visit. The associations of systolic and diastolic BP at baseline with incident hypertension at follow-up were explored in sex specific multivariable logistic regression analyses. Multivariable analysis looking at high-normal diastolic BP was adjusted for baseline BMI, systolic BP, high-normal diastolic BP , heart rate, physical activity, daily smoker, cholesterol, triglycerides. Multivariable analysis looking at high-normal systolic BP was adjusted for baseline BMI, diastolic BP, high normal systolic BP , heart rate, physical activity, daily smoker, cholesterol, triglyceride. Results are presented as odds ratios (OR), 95% confidence intervals (CI) and p-values.

Results

At baseline, average BP was 119/73 mmHg in women and 126/76 mmHg in men (p<0.001). A high-normal systolic BP was found in 16% of women and 35% of men (p< 0.001). A high-normal diastolic BP was found in 7% of women and 11% of men(p=0.008). After 26 years of follow-up, 39% of women and 45% of men had developed hypertension (p<0.05). In multivariable logistic regression analyses, high-normal systolic and diastolic BP at baseline predicted incident hypertension at follow up in both sexes (Table 1). High-normal systolic BP was a significantly stronger predictor for incident hypertension in women (OR 2.32, CI 1.5-3.5) with p<0.01 for sex interaction (Table 1). In men, high-normal diastolic BP at baseline, was the strongest predictor of incident hypertension (OR 2.1, 95% CI 1.2-3.7), but no sex-interaction was found for high-normal diastolic BP, possibly due to low numbers.

Conclusions

Having a high-normal systolic BP in early midlife is a greater risk for developing hypertension later in life for women than men.Table 1
Aspirin overuse in primary prevention: nationwide temporal trends in low-dose aspirin therapy for primary prevention of cardiovascular disease in adults with and without diabetes
Authors: Kristensen A M D , Pareek M , Kragholm K , Torp-Pedersen C , Mcevoy J W , Prescott E
Published: November 2023

Background

Aspirin therapy for primary prevention of cardiovascular disease (CVD) is controversial. European Society of Cardiology guideline recommendations have changed in the last decades, and aspirin is currently not recommended in individuals with low/moderate cardiovascular (CV) risk but may be considered in high-risk individuals with diabetes.

Purpose

We report temporal trends in primary prevention aspirin prescription among individuals with and without diabetes and describe characteristics of incident aspirin users.

Methods

Using Danish nationwide registries, we identified incident and prevalent aspirin users in a population ≥40 years without CVD, eligible for primary preventive aspirin therapy from 2000 through 2020. Temporal trends in aspirin use with and without diabetes were assessed, as were CV risk factors among incident users. Individuals in Denmark are primarily seen by general practitioners who have a gate-keeper function for secondary hospital-based care.

Results

A total of 522,680 individuals started aspirin therapy during the study period. The number of incident users peaked in 2002 (39,803 individuals, 1.78% of the eligible population) and was lowest in 2019 (11,898 individuals, 0.49%), with similar trends for subjects with and without diabetes (Figure 1). A large proportion of incident users had no CV risk factors (diabetes, hypertension, hypercholesterolemia, or chronic obstructive pulmonary disease [a proxy for smoking]); however, this proportion decreased from 53.9% in 2000 to 30.9% in 2020 (Figure 2). The number of prevalent aspirin users peaked at 7.7% in 2008 and was 3.3% in 2020. For subjects with diabetes, the peak was observed in 2009 at 38.5% and decreased to 17.1% in 2020.

Conclusion

Prescription of aspirin for primary prevention of CVD has decreased over the last two decades in individuals both with and without diabetes. However, aspirin appears to be inappropriately prescribed in many primary prevention adults as a large proportion of incident users had no CV risk factors. Efforts to inform appropriate prescription of aspirin are needed, e.g., by improved guidance for general practitioners.Figure 1Figure 2
The risk of cardiovascular disease or death among a healthy population with mildly reduced and preserved left ventricular ejection fraction
Authors: Sintov G , Peles I , Novak L , Abayev M , Shmueli H , Kobal S L
Published: November 2023

Aims

We investigated the relationship between mildly reduced and preserved left ventricular ejection fraction (LVEF) and cardiovascular morbidity and all-cause mortality, in a healthy community-based cohort.

Methods and results

A total of 20,385 echocardiograms of healthy individuals with LVEF≥45%, were collected at a tertiary university medical center, between 2002-2015. Participants were divided into three groups: 209 with mildly reduced (45-50%), 1,709 with preserved (50-55%), and 18,467 with normal (>55%) LVEF. Based on data from electronic medical records and multiple Cox regression analyses, we examined all-cause mortality (primary outcome) and major adverse cardiovascular events (MACE) which included: stable ischemic heart disease, acute coronary syndrome, heart failure, percutaneous coronary intervention, coronary artery bypass graft, and stroke (secondary outcome). The mean follow-up period was 7±4 years. Mean age was 33±10 years, 52.6% were females. Prevalence of death and MACE was 2.9% and 31% for mildly reduced LVEF, 1.8% and 10% for preserved LVEF, and 0.7% and 7.4% for normal LVEF, respectively. In multivariable-adjusted analyses, mildly reduced LVEF was related to increased risk of death [hazard ratio (HR) 3.58; 95% confidence interval (CI) 1.55-8.28] and MACE [HR 4.31; 95% CI 3.21- 5.79], followed by preserved LVEF ([HR 2.38; 95% CI 1.57-3.62] and [HR 1.36; 95% CI 1.14-1.61] for death and MACE, respectively), compared to normal LVEF.

Conclusion

In a healthy adult population, mildly reduced and preserved LVEF are associated with gradually higher all-cause mortality and cardiovascular morbidity, compared to normal LVEF. These results suggest that LVEF should be used as a novel parameter in cardiovascular disease prediction algorithms to reduce the prevalence of cardiovascular morbidity and mortality.
Coronary artery calcium score is a predictive tool for cardiovascular events in an asymptomatic population
Authors: Sousa F , Mendonca M I , Temtem M , Serrao M , Santos M , Sa D , Borges S , Freitas S , Henriques E , Rodrigues M , Drumond A , Sousa A C , Palma Dos Reis R
Published: November 2023

Background

Recent research highlights the role of the coronary artery calcium score (CAC Score) in evaluating the severity of subclinical atherosclerosis in asymptomatic individuals without apparent cardiovascular disease (CVD). However, the influence of the CAC score on the prognosis of an asymptomatic population is not consensual.

Objective

Investigate the role of the CAC score as a predictive tool for the occurrence of cardiovascular events in an asymptomatic population without known CVD.

Methods

1195 asymptomatic subjects (mean age 55.1±6.9 years, 73.8% male) selected from the prospective arm of the GENEMACOR study were followed up during 5.9±4.3 years. CAC score was performed by cardiac computed tomography and reported as Agatston units according to the Hoff Nomogram in low, moderate and high-risk categories. The bivariate analysis evaluated CV events in the three CAC score risk categories and in traditional risk factors (TRFs) individually. Multivariable Cox proportional hazard ratios (HR) with 95% conﬁdence intervals (95% CI) assessed the variables independently associated with CV events occurrence. Kaplan-Meier estimated the survival in the CAC risk categories.

Results

None of the TRFs showed significant differences in the CV events percentages. As the CAC score category increases, the percentage of CV events rises (p<0.0001). After Cox regression analysis, the high CAC risk category remained a strong CV events predictor (HR=3.71; 95% CI 1.66-8.27; p=0.001), along with age and smoking (Table). At fifteen years of follow-up, 95.3%, 92.8%, and 84.3% survived in the low, moderate and high-risk categories, respectively (Long Rank test; p<0.0001).

Conclusion

The presence of coronary calcifications indicated a worse prognosis in our asymptomatic population. CAC score is an excellent predictive tool for the asymptomatic subjects with coronary atherosclerosis in progression and could help initiate preventive therapy.
The concentration of small-diameter HDL particles (HDLp1) predicts the incidence of coronary calcium score in diabetic subjects without established cardiovascular disease
Authors: Carvalho L S F , Teles S B S , Bittencourt M S , Santos R D , Blaha M , Jones S , Toth P , Lotufo P , Bensenor I , Ramalho S H
Published: November 2023

Introduction

Type 2 diabetes (DM2) decisively influences the evolution of coronary atherosclerosis. However, this is a heterogeneous and poorly understood process. While in 50% of diabetics the chance of incident Coronary Calcium Score (CAC) in 5 years exceeds 40%, in 10% of diabetics the chance of incident CAC is less than 10%. To better understand the progression of coronary atherosclerosis measured by CAC in diabetics without cardiovascular disease, we studied the impact of the concentration of the small-diameter subfraction of HDL (HDLp1, 7 to 8nm). HDLp1 has been implicated as a central mediator of the anti-inflammatory effect of the HDL pool and could play a specific role in CAC incidence among diabetics.

Methods

From 2370 individual with two CAC evaluations and hydrogen spectroscopy/magnetic resonance (H1-NMR) plasma profile available, we found 461 diabetic individuals, non-users of statins, without previous cardiovascular disease, with CAC=0 in the first measurement and a second CAC measurement after an average period of 5 years. [HDLp1] concentration was measured by H1-NMR and divided into tertiles. The incidence of CAC was defined as an initial CAC of 0 followed by CAC>0 in the second measurement. Stepwise forward logistic regressions were used to identify risk factors for CAC incidence. Discrimination analysis was performed by calculating the area under the ROC curve (AUROC).

Results

A total of 143 (31.0%) patients had incident CAC. In stepwise logistic regression, alongside factors such as age, gender, systolic blood pressure, smoking, LDL-C, C-reactive protein and HbA1c, the 3rd tertile of [HDLp1] was associated with 55.2% (95% CI 15-110%, p =0.0039) and 140% (95% CI 32-341%, p<0.001) higher risk of CAC incidence compared to the 2nd tertile and 1st tertile, respectively. When compared to a model composed of 10 confounding variables (age, gender, systolic blood pressure, BMI, smoking, Lp(a), LDL-C,triglycerides, C-reactive protein and HbA1c) for predicting the incidence of CAC, the diameter of HDLp1 substantially increased the AUROC from 0.651 (95% CI 0.597-0.705) to 0.684 (95% CI 0.631–0.736), p=0.027 for the DeLong test comparing AUROCs. A restricted cubic spline demonstrated a strong association between [HDLp1] and CAC incidence.

Conclusion

The concentration of HDLp1 improves the predictive capacity for the incidence of CAC in diabetic individuals, non-users of statins, without cardiovascular disease.Spline HDLp1 concentration vs CAC incideROC for incident CAC
Lower income is associated with non-persistence to statin treatment after a first myocardial infarction
Authors: Ma K , Ohm J , Yip Lundstrom L , Yari A , Jernberg T , Svensson P
Published: November 2023

Introduction

Low socioeconomic status (SES), characterized by low education level and/or income, is associated with increased incidence and mortality in cardiovascular diseases (CVD) and recurrent atherosclerotic cardiovascular diseases (rASCVD) even in countries with universal healthcare. Treatment with statins is a cornerstone in the secondary prevention after myocardial infarction (MI) that reduces the risk for rASCVD and mortality. Mechanisms for how SES affects outcome post-MI are largely unknown.

Aim

The aim of this study was to investigate the association between low SES and non-persistence to statin treatment in the stable phase after a MI as a potential mediator for poorer outcome in those with low SES.

Methods

Nationwide Swedeheart registry-based cohort study on 63,900, 18–80-year-old survivors of a first MI (15,792 women) between 2006-2020 that participated in the follow-up after MI and claimed a statin-prescription (ATC-code C10AA) ≤120 days after the one-year revisit. Patients with previous history of CVD including stroke were excluded. Primary exposure was disposable income the year before MI divided into quintiles, stratified by income year and sex. Education level in three categories was investigated as a secondary exposure. The outcome was defined as time to first non-persistence to statin therapy where non-persistence was defined as a period over 180 days without expediting a new prescription. Hazard ratios (HR) with 95% CI were calculated for associations between income-quintile and non-persistence using Cox-regression adjusted for confounders (sex, age, inclusion-year, region of birth).

Results

During a median (IQR) follow-up on 7.47 years (3.7-11.2), 29,922 (46.8%) patients became non-persistent to statin treatment. An association between lower income and non-persistence was observed with a gradually increased risk for non-persistence in the lower income quintiles (table 1 and figure 1). The hazard ratio for non-persistence in the lowest compared to the highest income quintile was 1.29 (95% CI 1.24-1.34). The risk for non-persistence associated with low income remained significant after adjusting for confounders, including region of birth, where the risk for non-persistence in the lowest compared to the highest quintile was 1.17 (95% 1.13-1.22). Education was not associated with non-persistence.

Conclusions

In a nationwide post-MI population with access to universal healthcare, a strong association between income and non-persistence to statins was observed. Non-persistence to statins may be an important mediator for the increased risk for recurrent cardiovascular events after MI in patients with lower income.
Attainment of the low-density lipoprotein cholesterol treatment target and prognosis of heterozygous familial hypercholesterolemia
Authors: Tada H , Nomura A , Usui S , Sakata K , Takamura M , Kawashiri M
Published: November 2023

Background and aims

No previous study has investigated the association between attainment of low-density lipoprotein (LDL) cholesterol treatment target and better prognosis in patients with familial hypercholesterolemia (FH). The current research aimed to examine the association between attainment of LDL cholesterol treatment target and major adverse cardiac events (MACEs) in patients with FH to validate the current LDL cholesterol treatment targets in primary (< 100 mg/dL) and secondary (< 70 mg/dL) prevention settings.

Methods

The data of patients with FH who were admitted to our university hospital between 2000 and 2020 and who were followed-up were retrospectively reviewed. The number of MACEs, including mortality associated with cardiovascular disease, unstable angina, and myocardial infarction per 1,000 person-years, was calculated for each stratum for the attainment of LDL cholesterol target.

Results

The median follow-up duration was 12.6 years. In total, 132 MACEs were recorded during the follow-up period. The numbers of patients who attained the LDL cholesterol target in the primary and secondary prevention groups were 228 (31.9%) and 40 (11.9%), respectively. The event rates per 1,000 person-years for LDL cholesterol levels of < 100 and ≥ 100 mg/dL in the primary prevention group were 2.6 and 4.4, respectively. The event rates per 1,000 person-years for LDL cholesterol levels of < 70 and ≥ 70mg/dL in the secondary prevention group were 15.3 and 27.5, respectively.

Conclusion

Attainment of the LDL cholesterol target is associated with better prognosis in patients with FH. However, the attainment rate is currently inadequate among Japanese.
The exposome and nutritional pharmacology and toxicology: a new application for metabolomics
Authors: Rushing Blake R , Thessen Anne E , Soliman Ghada A , Ramesh Aramandla , Sumner Susan C J ,   Members of the Exposomics Consortium
Published: November 2023

The exposome refers to all of the internal and external life-long exposures that an individual experiences. These exposures, either acute or chronic, are associated with changes in metabolism that will positively or negatively influence the health and well-being of individuals. Nutrients and other dietary compounds modulate similar biochemical processes and have the potential in some cases to counteract the negative effects of exposures or enhance their beneficial effects. We present herein the concept of Nutritional Pharmacology/Toxicology which uses high-information metabolomics workflows to identify metabolic targets associated with exposures. Using this information, nutritional interventions can be designed toward those targets to mitigate adverse effects or enhance positive effects. We also discuss the potential for this approach in precision nutrition where nutrients/diet can be used to target gene-environment interactions and other subpopulation characteristics. Deriving these “nutrient cocktails” presents an opportunity to modify the effects of exposures for more beneficial outcomes in public health.
The moderating influence of celebrity endorsement on intention to engage in infection prevention behaviours
Authors: Coffie Isaac Sewornu , Tweneboah-Koduah Ernest Yaw , Ocloo Elikem Chosniel , Mann Victoria
Published: November 2023

Although the use of celebrities for communication within social marketing to influence voluntary behaviour change has received significant attention, its application to promote infection preventive behaviours, such as frequent handwashing with soap, has received limited attention. Using the health belief model (HBM), the study examined the moderating effect of celebrity endorsement (CE) on the relationship between the predictors of HBM such as perceived severity, susceptibility, benefits, barriers, self-efficacy and target audiences’ intention to avoid handshaking, frequently wash hands with soap and cover mouth with an elbow when coughing. Data from 562 respondents were analysed using PLS-SEM. The result shows that CE significantly moderate the relationship between target audiences’ perception of severity, susceptibility, self-efficacy and cues to action and intention to perform the recommended infection preventive behaviours. Thus, when a celebrity is employed as a conduit for delivering a social marketing message, particularly about infection preventive behaviour, target audiences are more likely to take action to perform the recommended behaviour. Theoretically, the study shows that although the HBM has been extensively applied to explain health-related behaviours, using celebrities to endorse the various constructs of the HBM significantly enhances the predictive ability of the model.
Efficacy of PD-1 checkpoint inhibitor therapy in melanoma and beyond: are peripheral T cell phenotypes the key?
Authors: Flaherty Katie R , Kucykowicz Stephanie , Schroth Johannes , Traves Will , Mincham Kyle T , Finney George E
Published: November 2023

Immunotherapy treatment strategies have proven effective in a limited portion of patients, where identifying responders from non-responders to treatment remains a challenge. While some indications can be drawn from invasive biopsies, we need more accessible methods for predicting response and better correlates of response prior to starting therapy. Recent work has identified differences in immune composition at baseline in peripheral blood from melanoma patients responding to PD-1 blockade treatment. Through flow cytometric analysis of T cell receptors, phenotypical features of CD8+ and CD4+ T cells and Tregs could allow for the stratification of treatment response. Analysing T cells within peripheral blood could potentially allow for the stratification of PD-1 treatment response prior to therapy in different cancer settings.
Second-Order Estimates for Transition Layers and a Curvature Estimate for the Parabolic Allen–Cahn
Authors: The Nguyen Huy , Wang Shengwen
Published: November 2023

The parabolic Allen–Cahn equation is a semilinear partial differential equation that is closely linked to the mean curvature flow by a singular perturbation. Motivated by the work of Wang–Wei [ 21] and Chodosh–Mantoulidis [ 3] in the elliptic setting, we initiate the corresponding regularity theory for parabolic Allen–Cahn flows. In particular, we establish an improved convergence property of parabolic Allen–Cahn flows to the mean curvature flow: if the phase-transition level sets converge in $C^{2}$, then they converge in $C^{2,\theta }$ as well. As an application, we obtain a curvature estimate for the parabolic Allen–Cahn equation, which can be seen as a diffused version of Brakke’s [ 1] and White’s [ 24] regularity theorems for mean curvature flow.
Generalizable pipeline for constructing HIV risk prediction models across electronic health record systems
Authors: May Sarah B , Giordano Thomas P , Gottlieb Assaf
Published: November 2023

Objective

The HIV epidemic remains a significant public health issue in the United States. HIV risk prediction models could be beneficial for reducing HIV transmission by helping clinicians identify patients at high risk for infection and refer them for testing. This would facilitate initiation on treatment for those unaware of their status and pre-exposure prophylaxis for those uninfected but at high risk. Existing HIV risk prediction algorithms rely on manual construction of features and are limited in their application across diverse electronic health record systems. Furthermore, the accuracy of these models in predicting HIV in females has thus far been limited.

Materials and methods

We devised a pipeline for automatic construction of prediction models based on automatic feature engineering to predict HIV risk and tested our pipeline on a local electronic health records system and a national claims data. We also compared the performance of general models to female-specific models.

Results

Our models obtain similarly good performance on both health record datasets despite difference in represented populations and data availability (AUC = 0.87). Furthermore, our general models obtain good performance on females but are also improved by constructing female-specific models (AUC between 0.81 and 0.86 across datasets).

Discussion and conclusions

We demonstrated that flexible construction of prediction models performs well on HIV risk prediction across diverse health records systems and perform as well in predicting HIV risk in females, making deployment of such models into existing health care systems tangible.
Deciphering the putative bioactive metabolites and the underlying mechanism of Juniperus horizontalis Moench (Creeping juniper) in the treatment of inflammation using network pharmacology and molecular docking
Authors: El-Banna Alaa A , Shawky Eman , Celik Ismail , Ghareeb Doaa A , Abdulmalek Shaymaa A , Darwish Reham S
Published: November 2023

Objectives

To investigate the chemical composition of the alcoholic extract from creeping juniper leaves using HPLC-MS/MS and to elucidate its potential anti-inflammatory mechanism through network-based pharmacology analysis to collectively enable a systematic exploration of the chemical composition, mechanism of action, and therapeutic potential of the alcoholic extract from creeping juniper leaves, providing valuable insights into its suitability as an anti-inflammatory agent.

Methods

Chemical profiling of the alcoholic extract of creeping juniper leaves using HPLC-MS/MS and revealing its anti-inflammatory mechanism using network-based pharmacology. Further, isolation of some of the identified biomarkers, assessment of their ex-vivo anti-inflammatory activity, and determination of their binding to pro-inflammatory cytokines using molecular docking and dynamics.

Key findings

Thirty-seven compounds were annotated and forwarded to network pharmacology analysis which revealed that the highest interactions were exhibited by quercetin, cosmosiin, myricetin, amentoflavone, hyperoside, isorhamnetin, and quercitrin whereas the most enriched inflammatory targets were IL-2, PGF, VEGFA, and TNFs. PI3K-Akt signaling pathway, arachidonic acid metabolism, and MAPK signaling pathway were found to be the most enriched ones. Six hit compounds were isolated and identified as hyperoside, quercetrin, cupressuflavone, hinokiflavone, amentoflavone, and quercetin. The isolated compounds showed strong anti-inflammatory activity against TNF-α, IL-6, and IL-1β, and molecular docking and dynamics simulation showed that quercetin, quercitrin, and hyperoside had the least binding energy with TNF-α, IL-6, and IL-1B, respectively.

Conclusions

Creeping juniper may reduce inflammation based on the suggested multi-compounds and multi-pathways, and that provided the basis for creeping juniper use as a potential anti-inflammatory drug.
A framework of biomarkers for skeletal aging: a consensus statement by the Aging Biomarker Consortium
Authors:   Aging Biomarker Consortium, Suo Jinlong , Gan Yibo , Xie Yangli , Xu Shuqin , Wang Jianfang , Chen Di , Chen Lin , Deng Lianfu , Feng Shiqing , Han Jingdong Jackie , Jiang Qing , Lei Guanghua , Liu Peng , Luo Xianghang , Ma Xin , Qu Jing , Song Chunli , Tang Peifu , Tang Tingting , Wang Sijia , Wei Xiaochun , Wu Chengtie , Xiao Guozhi , Yang Liu , Zhang Licheng , Zhang Weiqi , Zhang Zhenlin , Liu Guang-Hui , Zhang Changqing , Pei Gang , Luo Jian , Yue Rui , Zou Weiguo
Published: November 2023

The skeleton is an important structural and metabolic organ in human body, while aging is the physiological basis for degenerative skeletal diseases. China has the largest aging population in the world and faces great challenges in preventing and managing diseases related to skeletal aging. To address these challenges, the Aging China Biomarkers Consortium (ABC) has reached an expert consensus on biomarkers of skeletal aging by synthesizing the literature and insights from scientists and clinicians. The consensus provides a comprehensive assessment of biomarkers associated with skeletal aging and proposes a systematic framework that categorizes biomarkers into three dimensions, namely, functional, structural, and humoral dimensions. Within each dimension, the ABC recommended clinical and evidential research-based biomarkers for physiological aging and degenerative pathologies of the skeleton. This expert consensus aims to lay the foundation for future studies to assess the prediction, diagnosis, early warning, and treatment of diseases associated with skeletal aging, with the ultimate goal of improving the skeletal health of elderly populations in China and around the world.
Morphology of the Female and Male Reproductive Tracts and More Data on the Spermatostyle in the Brazilian Gyretes sp. (Coleoptera, Adephaga, Gyrinidae)
Authors: Salazar Karen , Novais Ademária , Lino-Neto José , Serrão José Eduardo
Published: November 2023

We investigated the male and female reproductive tracts of Gyretes sp. with light and transmission electron microscopies. The male has a pair of testes with a single coiled follicle, followed by short efferent ducts, which have a similar shape and diameter to the testes. Long ducts (epididymides) with differential epithelium open in a pair of long vasa deferentia that lead to the accessory glands. Glycoprotein secretions from the vas deferens epithelium constitute the spermatostyle for spermatozoa aggregation. The female has numerous ovarioles per ovary, a coiled fertilization duct, an accessory gland, and an elongated vagina. Spermatozoa are stored as unaggregated cells in the fertilization duct. In Gyrinidae, the testes and accessory glands show diverse shapes, and the female sperm storage organs vary in shape, size, and type and may play a role in the interaction with sperm aggregates. Testes with a single follicle and vasa deferentia opening in the accessory glands of Gyretes sp. are features shared with other Gyrinidae and other Adephaga. We proposed adding this latter trait to characterize this suborder of beetles. The morphology of the reproductive organs in both sexes contributes to comparative analyses and knowledge of the reproductive biology of Gyretes and may provide additional features for systematics.
Weak secondary cyclotron line in eclipsing high-mass X-ray binary Cen X-3
Authors: Dangal Pravat , Misra Ranjeev , Chakradhari N K , Bhulla Yashpal
Published: November 2023

We report the time-resolved spectroscopy results from two observations of Centaurus X-3, over one binary orbit with AstroSat and two binary orbits with Nuclear Spectroscopic Telescope Array (NuSTAR). NuSTAR covered two intensity states where the light curve showed transition in count rate from first to second binary orbit by a factor of ∼3. A phenomenological model comprising of partially absorbed power law with smoothed high energy cutoff, cyclotron absorption ∼24 and 6.4 keV iron emission gave good fit for AstroSat observation. NuSTAR spectra required two additional emission components, a broad one ∼5.7 keV and a narrow one ∼6.9 keV. A weak secondary absorption feature at ∼11.6 and ∼ 14.5 keV was seen in the residuals of the spectral fit for AstroSat and NuSTAR data, respectively. The secondary absorption energy showed no correlation with the cutoff energy. Its strength varied within 0.1–0.6 keV with its width ∼1.6 keV. Its energy and optical depth showed linear positive correlation with the fundamental cyclotron line energy and depth, respectively. The cyclotron line energy showed anticorrelation to flux described by a power law with negative index and the secondary absorption also showed similar trend to flux. Depth of secondary absorption was ∼45 per cent and centroid energy was ∼54 per cent of fundamental. Depth and energy ratio of secondary to fundamental lied within 2σ deviation from 0.5. We suggest this secondary absorption to be a redshifted dipolar cyclotron resonance feature exhibiting sub-harmonic behaviour.
Expression Atlas update: insights from sequencing data at both bulk and single cell level
Authors: George Nancy , Fexova Silvie , Fuentes Alfonso Munoz , Madrigal Pedro , Bi Yalan , Iqbal Haider , Kumbham Upendra , Nolte Nadja Francesca , Zhao Lingyun , Thanki Anil S , Yu Iris D , Marugan Calles Jose C , Erdos Karoly , Vilmovsky Liora , Kurri Sandeep R , Vathrakokoili-Pournara Anna , Osumi-Sutherland David , Prakash Ananth , Wang Shengbo , Tello-Ruiz Marcela K , Kumari Sunita , Ware Doreen , Goutte-Gattat Damien , Hu Yanhui , Brown Nick , Perrimon Norbert , Vizcaíno Juan Antonio , Burdett Tony , Teichmann Sarah , Brazma Alvis , Papatheodorou Irene
Published: November 2023

Expression Atlas (www.ebi.ac.uk/gxa) and its newest counterpart the Single Cell Expression Atlas (www.ebi.ac.uk/gxa/sc) are EMBL-EBI’s knowledgebases for gene and protein expression and localisation in bulk and at single cell level. These resources aim to allow users to investigate their expression in normal tissue (baseline) or in response to perturbations such as disease or changes to genotype (differential) across multiple species. Users are invited to search for genes or metadata terms across species or biological conditions in a standardised consistent interface. Alongside these data, new features in Single Cell Expression Atlas allow users to query metadata through our new cell type wheel search. At the experiment level data can be explored through two types of dimensionality reduction plots, t-distributed Stochastic Neighbor Embedding (tSNE) and Uniform Manifold Approximation and Projection (UMAP), overlaid with either clustering or metadata information to assist users’ understanding. Data are also visualised as marker gene heatmaps identifying genes that help confer cluster identity. For some data, additional visualisations are available as interactive cell level anatomograms and cell type gene expression heatmaps.
Job creation and deep decarbonization
Authors: Gallagher Kelly Sims , Oh Soyoung
Published: November 2023

This paper explores whether economic viability is the key to achieve deep decarbonization or net zero emissions. The hypothesis tested is that popular support for decarbonization policies is conditional upon most people’s belief that their economic well-being will improve, or at least not suffer with these policies. While GDP growth is the typical metric for economic health, a more useful socio-economic indicator for gauging the political viability of climate policies may be job creation. Specifically, the paper reviews the existing evidence about whether climate policies are more successful in achieving deep decarbonization in the long run if policy-makers include job creation as well as emissions reductions when designing and implementing climate policies, because, to date, climate policy-makers have often focused on emissions reductions as the primary criterion for policy choice. While empirical evidence remains thin, we find that job creation in low-carbon industries appears to lead to greater political support for the climate policies that contribute to decarbonization, but employment factors are not always the most salient factor in a voter’s decision. We also find empirical evidence that clean energy deployment policies, such as feed-in tariffs, have led to significant net gains in employment in the countries that have been studied. The review points to several policy implications, including the need to assess competitive advantage, develop plans, design and execute industrial policy, and develop a low-carbon workforce.
The conflict of impact for early career researchers planning for a future in the academy
Authors: Wróblewska Marta Natalia , Balaban Corina , Derrick Gemma , Benneworth Paul
Published: November 2023

It has been argued that due to the growing importance attributed to research impact and forms of its evaluation, an academic ‘culture of impact’ is emerging. It would include certain concepts, values, and skills related to the area of generating and documenting impact. We use thematic and discourse analysis to analyse open answers from 100 questionnaires on research impact submitted by ECRs working in the social sciences and humanities (SSH) in Europe. We explore ECR’s early-career stage positions relative to societal impact and the trade-offs necessary to assure an academic career. The results show how, as the first generation of scholars to be socialized towards value of academic research beyond academia, ECRs are confronted with policy signals that encourage a drive for impact, which are at the same time often in line with respondents’ personal values around impact beyond academia. However, ECRs face a number of competing signals about research value within the evaluation spaces necessary to navigate an academic career. Current evaluative structures often dismiss the achievement of societal impact favouring instead narrower definitions of research excellence. Career structures and organizational realities are often unfavourable to impact-related activity, which has implications for an ECRs’ ability to develop coherent professional positionings.
Pay, Stay, or Delay? How to Settle a Run
Authors: Matta Rafael , Perotti Enrico
Published: November 2023

The classic view assumes banks prioritize immediate repayment by selling assets until default. We endogenize run frequency and study how general settlement rules trade off liquidity provision net of fire sale losses against induced run incentives. Panic runs are eliminated when all illiquid assets are sold under orderly resolution, but liquidity provision in a run is minimal. When suspension after some fire sales is followed by immediate liquidation, run frequency falls then rises in suspension delay. Thus, optimal suspension may require some sale of illiquid assets, in contrast to MMF norms. Ex post discretion induces excessive liquidation and more frequent runs. (JEL D8, G21)
Integration of Transcriptomic Features to Improve Prognosis Prediction of Pediatric Acute Myeloid Leukemia With KMT2A Rearrangement
Authors: Li Jun , Zong Suyu , Wan Yang , Ruan Min , Zhang Li , Yang Wenyu , Chen Xiaojuan , Zou Yao , Chen Yumei , Guo Ye , Wu Peng , Zhang Yingchi , Zhu Xiaofan
Published: November 2023

Lysine methyltransferase 2A-rearranged acute myeloid leukemia (KMT2A-r AML) is a special entity in the 2022 World Health Organization classification of myeloid neoplasms, characterized by high relapse rate and adverse outcomes. Current risk stratification was established on the treatment response and translocation partner of KMT2A. To study the transcriptomic feature and refine the current stratification of pediatric KMT2A-r AML, we analyzed clinical and RNA sequencing data of 351 patients. By implementing least absolute shrinkage and selection operator algorithm, we identified 7 genes (KIAA1522, SKAP2, EGFL7, GAB2, HEBP1, FAM174B, and STARD8) of which the expression levels were strongly associated with outcomes. We then developed a transcriptome-based score, dividing patients into 2 groups with distinct gene expression patterns and prognosis, which was further validated in an independent cohort and outperformed the LSC17 score. We also found cell cycle, oxidative phosphorylation, and metabolism pathways were upregulated in patients with inferior outcomes. By integrating clinical characteristics, we proposed a simple-to-use prognostic scoring system with excellent discriminability, which allowed us to distinguish allogeneic hematopoietic stem cell transplantation candidates more precisely. In conclusion, pediatric KMT2A-r AML is heterogenous on transcriptomic level and the newly proposed scoring system combining clinical characteristics and transcriptomic features can be instructive in clinical routines.
Systematic Review and Meta-analysis of Laparoscopic Versus Open Radical Nephrectomy for Paediatric Renal Tumours with Focus on Wilms’ Tumour
Authors: Mentessidou Anastasia , Djendov Florin , Long Anna-May , Jackson Claire
Published: November 2023

Objective:

To summarize and evaluate the outcomes of laparoscopic radical nephrectomy (LRN) and compare its safety and efficacy with open radical nephrectomy (ORN) in paediatric renal tumours (RT) and Wilms’ tumour (WT).

Summary Background Data:

ORN is the gold standard treatment for paediatric RT, consisting predominantly of WT. LRN is gaining popularity but remains controversial in paediatric surgical oncology.

Methods:

Systematic search was performed for all eligible studies on LRN and comparative studies between LRN and ORN in paediatric RT and WT. Meta-analysis, subgroup analysis and sensitivity analysis were conducted. Main endpoints were the cancer-related outcomes and surgical morbidity. PRISMA guidelines were followed.

Results:

No level I-II studies were identified. LRN was feasible in nearly 1 in 5 paediatric RT and WT after neoadjuvant chemotherapy, with pooled mid-term oncological outcomes (<7% local recurrence, >90% event-free survival) comparable with those of ORN. There was no strong evidence of increased risk of intraoperative tumour spillage, but lymph node harvest was inadequate in LRN. Large tumours crossing the ipsilateral spinal border were associated with a trend for intraoperative complications and positive margins. Pooled complications rate and hospital stay duration were similar between LRN and ORN. Long-term (>3-year) outcomes are unknown.

Conclusions:

Available level III evidence indicates that LRN is a safe alternative to ORN for carefully selected cases, with similar spillage rates and mid-term oncological outcomes. However, there was no advantage in surgical morbidity and lymph node harvest was inadequate with LRN. Tumour matched-group studies with long-term follow-up are required.

Level of Evidence:

III
Unspoken Truths
Authors: Collins Reagan A. , Herman Tianna , Snyder Rebecca A. , Haines Krista L , Stey Anne , Arora Tania K. , Geevarghese Sunil K. , Phillips Joseph D. , Vicente Diego , Griggs Cornelia L. , McElroy Imani E , Wall Anji E. , Hughes Tasha M. , Sen Srijan , Valinejad Jaber , Alban Andres , Swan J. Shannon , Mercaldo Nathaniel , Jalali Mohammad S. , Chhatwal Jagpreet , Gazelle G. Scott , Rangel Erika , Yang Chi-Fu Jeffrey , Donelan Karen , Gold Jessica A. , West Colin P. , Cunningham Carrie
Published: November 2023

Objective:

To characterize the current state of mental health within the surgical workforce in the United States (US).

Summary Background Data:

Mental illness and suicide is a growing concern in the medical community; however, the current state is largely unknown.

Methods:

Cross-sectional survey of the academic surgery community assessing mental health, medical error, and suicidal ideation. The odds of suicidal ideation adjusting for sex, prior mental health diagnosis, and validated scales screening for depression, anxiety, post-traumatic stress disorder (PTSD), and alcohol use disorder were assessed.

Results:

Of 622 participating medical students, trainees, and surgeons (estimated response rate=11.4-14.0%), 26.1% (141/539) reported a previous mental health diagnosis. 15.9% (83/523) of respondents screened positive for current depression, 18.4% (98/533) for anxiety, 11.0% (56/510) for alcohol use disorder, and 17.3% (36/208) for PTSD. Medical error was associated with depression (30.7% vs. 13.3%, P<0.001), anxiety (31.6% vs. 16.2%, P=0.001), PTSD (12.8% vs. 5.6%, P=0.018), and hazardous alcohol consumption (18.7% vs. 9.7%, P=0.022). 13.2% (73/551) of respondents reported suicidal ideation in the past year and 9.6% (51/533) in the past two weeks. On adjusted analysis, a previous history of a mental health disorder (aOR: 1.97, 95% CI: 1.04-3.65, P=0.033), and screening positive for depression (aOR: 4.30, 95% CI: 2.21-8.29, P<0.001) or PTSD (aOR: 3.93, 95% CI: 1.61-9.44, P=0.002) were associated with increased odds of suicidal ideation over the past 12 months.

Conclusions:

Nearly 1 in 7 respondents reported suicidal ideation in the past year. Mental illness and suicidal ideation are significant problems among the surgical workforce in the US.
A Conduit for a Culturally Competent Consent
Authors: Allar Benjamin G. , Ponce Cristina , Wallace James , Ortega Gezzer , Reich Amanda J. , Gold-Gomez Shari , Gangadharan Sidhu P. , Kent Tara S.
Published: November 2023

Objective:

To understand medical interpreter’s perspectives on surgical informed consent discussions and provide feedback for surgeons on improving these conversations.

Summary Background Data:

Informed consent is a critical component of patient-centered surgical decision-making. For patients with limited English proficiency (LEP), this conversation may be less thorough, even with a medical interpreter, leaving patients with an inadequate understanding of their diagnosis or treatment options.

Methods:

A semi-structured interview guide was developed with input from interpreters and a qualitative research expert. We purposively sampled medical interpreters representing multiple languages until thematic saturation was achieved. Participants discussed their experience with the surgical consent discussion and process. Interview transcripts were analyzed using emergent thematic analysis.

Results:

Among 22 interpreters, there were ten languages represented and an average experience of 15 years (range 4-40 y). Four major themes were identified. First, interpreters consistently described their roles as patient advocates and cultural brokers. Second, interpreters reported unique patient attributes that influence the discussion, often based on patients’ cultural values/expectations, anticipated decisional autonomy, and family support. Third, interpreters emphasized the importance of surgeons demonstrating compassion and patience, using simple terminology, conversing around the consent, providing context about the form/process, and initiating a pre-encounter discussion. Finally, interpreters suggested reducing legal terminology on consent forms and translation into other languages.

Conclusions:

Experienced interpreters highlighted multiple factors associated with effective and culturally tailored informed consent discussions. Surgeons should recognize interpreters’ critical and complex roles, be cognizant of cultural variations among patients with LEP, and improve interpersonal and communication skills to facilitate effective understanding.
Evolution in Laparoscopic Gastrectomy from a Randomized Controlled Trial through National Clinical Practice
Authors: Markar Sheraz R. , Visser Maurits , van der Veen Arjen , Luyer Misha , Nieuwenhuijzen Grard AP , Stoot Jan HMB , Tegels Juul JW , Wijnhoven Bas , Lagarde Sjoerd , de Steur Wobbe O. , Hartgrink Henk H. , Kouwenhoven Ewout A. , Wassenaar Eelco B. , Draaisma Werner A. , Gisbertz Suzanne S. , van Berge Henehouwen Mark , van der Peet Donald L. , Ruurda Jelle , van Hillegersberg Richard ,   LOGICA Study group, Dutch Upper Gastrointestinal Cancer Audit Group
Published: November 2023

Objective:

To examine the influence of the LOGICA RCT upon the practice and outcomes from laparoscopic gastrectomy within the Netherlands.

Background:

Following RCTs the dissemination of complex interventions has been poorly studied. The LOGICA RCT included 10 Dutch centers and compared laparoscopic to open gastrectomy.

Methods:

Data were obtained from the Dutch Upper Gastrointestinal Cancer Audit (DUCA) on all gastrectomies performed in the Netherlands (2012–2021), and the LOGICA RCT from (2015–2018). Multilevel multivariable logistic regression analyses were performed to assess the effect of laparoscopic versus open gastrectomy upon clinical outcomes before, during and after the LOGICA RCT.

Results:

211 patients from the LOGICA RCT (105 open vs. 106 laparoscopic) and 4,131 patients from the DUCA dataset (1884 open vs. 2247 laparoscopic) were included. In 2012, laparoscopic gastrectomy was performed in 6% of patients, increasing to 82% in 2021. No significant effect of laparoscopic gastrectomy on postoperative clinical outcomes was observed within the LOGICA RCT. Nationally within DUCA, a shift towards a beneficial effect of laparoscopic gastrectomy upon complications was observed, reaching a significant reduction on overall (aOR:0.62; 95%CI:0.46-0.82), severe (aOR:0.64; 95%CI:0.46-0.90) and cardiac complications (aOR:0.51; 95%CI:0.30-0.89) after the LOGICA trial.

Conclusion:

The wider benefits of the LOGICA trial included safe dissemination of laparoscopic gastrectomy across the Netherlands. The robust surgical quality assurance programme in the design of the LOGICA RCT was crucial to facilitate the national dissemination of the technique following the trial and reducing potential patient harm during surgeons learning curve.