bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine learning for parameters diagnosis of spark discharge by electro-acoustic signal
Authors: XIONG 熊 Jun 俊 , LU 卢 Shiyu 诗宇 , LIU 刘 Xiaoming 晓明 , ZHOU 周 Wenjun 文俊 , ZHA 查 Xiaoming 晓明 , PEI 裴 Xuekai 学凯
Published: May 2024

Discharge plasma parameter measurement is a key focus in low-temperature plasma research. Traditional diagnostics often require costly equipment, whereas electro-acoustic signals provide a rich, non-invasive, and less complex source of discharge information. This study harnesses machine learning to decode these signals. It establishes links between electro-acoustic signals and gas discharge parameters, such as power and distance, thus streamlining the prediction process. By building a spark discharge platform to collect electro-acoustic signals and implementing a series of acoustic signal processing techniques, the Mel-Frequency Cepstral Coefficients (MFCCs) of the acoustic signals are extracted to construct the predictors. Three machine learning models (Linear Regression, k-Nearest Neighbors, and Random Forest) are introduced and applied to the predictors to achieve real-time rapid diagnostic measurement of typical spark discharge power and discharge distance. All models display impressive performance in prediction precision and fitting abilities. Among them, the k-Nearest Neighbors model shows the best performance on discharge power prediction with the lowest mean square error (MSE = 0.00571) and the highest

-squared value (

). The experimental results show that the relationship between the electro-acoustic signal and the gas discharge power and distance can be effectively constructed based on the machine learning algorithm, which provides a new idea and basis for the online monitoring and real-time diagnosis of plasma parameters.
On the pointwise regularity of the Multifractional Brownian Motion and some extensions
Authors: Esser C. , Loosveldt L.
Published: May 2024

We study the pointwise regularity of the Multifractional Brownian Motion and, in particular, we obtain the existence of so-called slow points of the process, that is points which exhibit a slow oscillation instead of the a.e. regularity. This result entails that a non self-similar process can also exhibit such a behavior. We also consider various extensions with the aim of imposing weaker regularity assumptions on the Hurst function without altering the regularity of the process.
Temporal properties of the stochastic fractional heat equation with spatially-colored noise
Authors: Wang Ran , Xiao Yimin
Published: May 2024

Consider the stochastic partial differential equation
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Characterization of the least squares estimator: Mis-specified multivariate isotonic regression model with dependent errors
Authors: Bagchi Pramita , Dhar Subhra
Published: May 2024

This article investigates some nice properties of the least squares estimator of multivariate isotonic regression function (denoted as LSEMIR), when the model is mis-specified, and the errors are

β
\beta

-mixing stationary random variables. Under mild conditions, it is observed that the least squares estimator converges uniformly to a certain monotone function, which is closest to the original function in an appropriate sense.
The Responsibility to Protect
Authors: Williams Abiodun
Published: May 2024

Chapter 5 explores Kofi Annan’s approach to the issue of humanitarian intervention, and his idea of two sovereignties—of states and of people. His conviction that sovereignty was not absolute but contingent, and was vested in a state’s citizenry, not just in the state itself, is central to understanding his Secretary-Generalship. He produced a UN Action Plan to Prevent Genocide and supported the establishment of the International Criminal Court. As a norm entrepreneur, he challenged member states to find a consensus on the vital issue of the international community’s responsibility in the face of mass atrocities. At the 2005 World Summit, all member states unanimously accepted their Responsibility to Protect civilians from four types of mass atrocity crimes: genocide, war crimes, ethnic cleansing, and crimes against humanity.
Dar es Salaam
Authors: Burton Eric
Published: May 2024

Dar es Salaam, a major urban center in early 21st-century East Africa, was founded in 1862 as a mainland outpost of the sultanate in Zanzibar. From its very beginnings, the town was a cosmopolitan, polyglot, and multiethnic space. Following colonial conquest, the Germans used Dar es Salaam as their capital of German East Africa from 1891 onward, as did the British administration of Tanganyika, as the territory was renamed after the transfer of power following World War I, until independence in 1961. Colonial rule shaped the city’s geography according to racialized zoning, yet both colonial and subsequent postcolonial governments often found themselves reacting to dynamics (particularly immigration and informalization) rather than initiating them. Since the late colonial period, social and political dynamics in Dar es Salaam—such as the growth of nationalism—have had repercussions in all of Tanzania. In the 1960s and 1970s, the city became a transnational revolutionary hub at the crossroads of Pan-Africanism, anticolonial currents, and Cold War rivalries. At the same time, at the national level, the government tried to peripheralize Dar es Salaam and announced the relocation of the capital to Dodoma in 1972. Despite the antiurban bias of Tanzania’s policies of African socialism (UJAMAA) and neoliberal reconfigurations from the 1980s onward, both of which put a brake on state investments in urban infrastructures and services, Dar es Salaam remained a commercial, cultural, and diplomatic center. With a population that grew from 22,500 in 1913 to 5.4 million inhabitants in 2022, it has become one of Africa’s major metropolises.
COSGAP: COntainerized Statistical Genetics Analysis Pipelines
Authors: Akdeniz Bayram Cevdet , Frei Oleksandr , Hagen Espen , Filiz Tahir Tekin , Karthikeyan Sandeep , Pasman Joëlle , Jangmo Andreas , Bergstedt Jacob , Shorter John R , Zetterberg Richard , Meijsen Joeri , Sønderby Ida Elken , Buil Alfonso , Tesli Martin , Lu Yi , Sullivan Patrick , Andreassen Ole A , Hovig Eivind
Published: May 2024

The collection and analysis of sensitive data in large-scale consortia for statistical genetics is hampered by multiple challenges, due to their non-shareable nature. Time-consuming issues in installing software frequently arise due to different operating systems, software dependencies, and limited internet access. For federated analysis across sites, it can be challenging to resolve different problems, including format requirements, data wrangling, setting up analysis on high-performance computing (HPC) facilities, etc. Easier, more standardized, automated protocols and pipelines can be solutions to overcome these issues. We have developed one such solution for statistical genetic data analysis using software container technologies. This solution, named COSGAP: “COntainerized Statistical Genetics Analysis Pipelines,” consists of already established software tools placed into Singularity containers, alongside corresponding code and instructions on how to perform statistical genetic analyses, such as genome-wide association studies, polygenic scoring, LD score regression, Gaussian Mixture Models, and gene-set analysis. Using provided helper scripts written in Python, users can obtain auto-generated scripts to conduct the desired analysis either on HPC facilities or on a personal computer. COSGAP is actively being applied by users from different countries and projects to conduct genetic data analyses without spending much effort on software installation, converting data formats, and other technical requirements.

Availability and implementation

COSGAP is freely available on GitHub (https://github.com/comorment/containers) under the GPLv3 license.
PathwayNexus: a tool for interactive metabolic data analysis
Authors: Eberhard Philipp , Kern Martin , Aichem Michael , Borlinghaus Hanna , Klein Karsten , Delp Johannes , Suciu Ilinca , Moser Benjamin , Dietrich Daniel , Leist Marcel , Schreiber Falk
Published: May 2024

Motivation

High-throughput omics methods increasingly result in large datasets including metabolomics data, which are often difficult to analyse.

Results

To help researchers to handle and analyse those datasets by mapping and investigating metabolomics data of multiple sampling conditions (e.g. different time points or treatments) in the context of pathways, PathwayNexus has been developed, which presents the mapping results in a matrix format, allowing users to easily observe the relations between the compounds and the pathways. It also offers functionalities like ranking, sorting, clustering, pathway views, and further analytical tools. Its primary objective is to condense large sets of pathways into smaller, more relevant subsets that align with the specific interests of the user.

Availability and implementation

The methodology presented here is implemented in PathwayNexus, an open-source add-on for Vanted available at www.cls.uni-konstanz.de/software/pathway-nexus.

Contact

falk.schreiber@unikonstanz.de

Supplementary information

Website: www.cls.uni-konstanz.de/software/pathway-nexus
Intraperitoneal chemotherapy for peritoneal metastases of gastric origin: a systematic review and meta-analysis
Authors: Guchelaar Niels A D , Nasserinejad Kazem , Mostert Bianca , Koolen Stijn L W , van der Sluis Pieter C , Lagarde Sjoerd M , Wijnhoven Bas P L , Mathijssen Ron H J , Noordman Bo J
Published: May 2024

Background

Gastric cancer with peritoneal metastases is associated with a dismal prognosis. Normothermic catheter-based intraperitoneal chemotherapy and normothermic pressurized intraperitoneal aerosol chemotherapy (PIPAC) are methods to deliver chemotherapy intraperitoneally leading to higher intraperitoneal concentrations of cytotoxic drugs compared to intravenous administration. We reviewed the effectiveness and safety of different methods of palliative intraperitoneal chemotherapy.

Methods

Embase, MEDLINE, Web of Science and Cochrane were searched for articles studying the use of repeated administration of palliative intraperitoneal chemotherapy in patients with gastric cancer and peritoneal metastases, published up to January 2024. The primary outcome was overall survival.

Results

Twenty-three studies were included, representing a total of 999 patients. The pooled median overall survival was 14.5 months. The pooled hazard ratio of the two RCTs using intraperitoneal paclitaxel and docetaxel favoured the intraperitoneal chemotherapy arm. The median overall survival of intraperitoneal paclitaxel, intraperitoneal docetaxel and PIPAC with cisplatin and doxorubicin were respectively 18.4 months, 13.2 months and 9.0 months. All treatment methods had a relatively safe toxicity profile. Conversion surgery after completion of intraperitoneal therapy was performed in 16% of the patients.

Conclusions

Repeated intraperitoneal chemotherapy, regardless of method of administration, is safe for patients with gastric cancer and peritoneal metastases. Conversion surgery after completion of the intraperitoneal chemotherapy is possible in a subset of patients.
The limits of waste as a resource: a critique and a proposition towards a new scalar imagination for the circular economy model
Authors: Zavos Stylianos , Pyyhtinen Olli
Published: May 2024

In the article, we critically confront the idea of waste-to-resource at the heart of the circular economy. We discuss some of the blind spots and shortcomings of three circular economy principles: designing out waste, emulating natural systems and decoupling economic growth from resource use. We suggest that their limitations are intimately connected to a scalar reasoning ruled by strict, disjunctive categories. Instead, we advance a flat, relational, trans-scalar approach and propose that the potential of a sustained circular economy promise requires a novel scalar imagination attentive to its multiple co-constituted spatialities, social relations and fluid materials.
SGLT2 inhibition to target kidney aging
Authors: Russo Elisa , Zanetti Valentina , Macciò Lucia , Benizzelli Giulia , Carbone Federico , La Porta Edoardo , Esposito Pasquale , Verzola Daniela , Garibotto Giacomo , Viazzi Francesca
Published: May 2024

Anti-aging therapy is the latest frontier in the world of medical science, especially for widespread diseases such as chronic kidney disease (CKD). Both renal aging and CKD are characterized by increased cellular senescence, inflammation and oxidative stress. A variety of cellular signalling mechanisms are involved in these processes, which provide new potential targets for therapeutic strategies aimed at counteracting the onset and progression of CKD. At the same time, sodium–glucose co-transporter 2 inhibitors (SGLT2is) continuously demonstrate large beneficial effects at all stages of the cardiorenal metabolic continuum. The broad-spectrum benefits of SGLT2is have led to changes in several treatment guidelines and to growing scientific interest in the underlying working principles. Multiple mechanisms have been studied to explain these great renal benefits, but many things remain to be solved. With this in mind, we provide an overview of the experimental evidence for the effects of SGLT2is on the molecular pathway’s ability to modulate senescence, aging and parenchymal damage, especially at the kidney level. We propose to shed some light on the role of SGLT2is in kidney care by focusing on their potential to reduce the progression of kidney disease across the spectrum of aging and dysregulation of senescence.
Tubular biomarkers in proteinuric kidney disease: histology correlation and kidney prognosis of tubular biomarkers
Authors: Carbayo Javier , Verdalles Úrsula , Díaz-Crespo Francisco , Lázaro Alberto , González-Nicolás Marian , Arroyo David , Blanco David , García-Gámiz Mercedes , Goicoechea Marian
Published: May 2024

Background

Proteinuria is not only a biomarker of chronic kidney disease (CKD) but also a driver of CKD progression. The aim of this study was to evaluate serum and urinary tubular biomarkers in patients with biopsied proteinuric kidney disease and to correlate them with histology and kidney outcomes.

Methods

A single-center retrospective study was conducted on a cohort of 156 patients from January 2016 to December 2021. The following urinary and serum biomarkers were analyzed on the day of kidney biopsy: beta 2 microglobulin (β2-mcg), alpha 1 microglobulin (α1-mcg), neutrophil gelatinase-associated lipocalin (NGAL), urinary kidney injury molecule-1 (uKIM-1), monocyte chemoattractant protein-1 (MCP-1), urinary Dickkopf-3 (uDKK3), uromodulin (urinary uUMOD), serum kidney injury molecule-1 (sKIM-1) and serum uromodulin (sUMOD). A composite outcome of kidney progression or death was recorded during a median follow-up period of 26 months.

Results

Multivariate regression analysis identified sUMOD (β–0.357, P < .001) and uDKK3 (β 0.483, P < .001) as independent predictors of interstitial fibrosis, adjusted for age, estimated glomerular filtration rate (eGFR) and log proteinuria. Elevated levels of MCP-1 [odds ratio 15.61, 95% confidence interval (CI) 3.52–69.20] were associated with a higher risk of cortical interstitial inflammation >10% adjusted for eGFR, log proteinuria and microhematuria. Upper tertiles of uDKK3 were associated with greater eGFR decline during follow-up. Although not a predictor of the composite outcome, doubling of uDKK3 was a predictor of kidney events (hazard ratio 2.26, 95% CI 1.04–4.94) after adjustment for interstitial fibrosis, eGFR and proteinuria.

Conclusions

Tubular markers may have prognostic value in proteinuric kidney disease, correlating with specific histologic parameters and identifying cases at higher risk of CKD progression.
Inhibition of TBL1 cleavage alleviates doxorubicin-induced cardiomyocytes death by regulating the Wnt/β-catenin signal pathway
Authors: Lee Sun-Ho , Lee Jangho , Oh Jaewon , Hwang Jin-Taek , Lee Hae-Jeung , Byun Hwa Kyung , Kim Hyeong-Jin , Suh David , Yoon Ho-Geun , Park Sahng Wook , Kang Seok-Min , Kwon Chulan , Lee Seung-Hyun , Choi Hyo-Kyoung
Published: May 2024

Aims

Doxorubicin (DOX) is a widely used anthracycline anticancer agent; however, its irreversible effects on the heart can result in DOX-induced cardiotoxicity (DICT) after cancer treatment. Unfortunately, the pathophysiology of DICT has not yet been fully elucidated, and there are no effective strategies for its prevention or treatment. In this investigation, the novel role of transducin beta-like protein 1 (TBL1) in developing and regulating DICT was explored.

Methods and results

We observed a reduction in TBL1 protein expression levels as well as cleavage events in the transplanted cardiac tissues of patients diagnosed with Dilated Cardiomyopathy and DICT. It was revealed that DOX selectively induces TBL1 cleavage at caspase-3 preferred sites—D125, D136, and D215. Interestingly, overexpression of the uncleaved TBL1 mutant (TBL1uclv) variant reduced apoptosis, effectively preventing DOX-induced cell death. We confirmed that cleaved TBL1 cannot form a complex with β-catenin. As a result, Wnt reporter activity and Wnt target gene expression collectively indicate a decrease in Wnt/β-catenin signalling, leading to DICT progression. Furthermore, the cleaved TBL1 triggered DOX-induced abnormal electrophysiological features and disrupted calcium homeostasis. However, these effects were improved in TBL1uclv-overexpressing human-induced pluripotent stem cell-derived cardiomyocytes. Finally, in a DICT mouse model, TBL1uclv overexpression inhibited the DICT-induced reduction of cardiac contractility and collagen accumulation, ultimately protecting cardiomyocytes from cell death.

Conclusion

Our findings reveal that the inhibition of TBL1 cleavage not only mitigates apoptosis but also enhances cardiomyocyte function, even in the context of DOX administration. Consequently, this study's results suggest that inhibiting TBL1 cleavage may be a novel strategy to ameliorate DICT.
Pan-Enteric Crohn’s Capsule [Eliakim] Score Reliability and Responsiveness to Change in Active Crohn’s Disease
Authors: Ukashi Offir , Lahat Adi , Ungar Bella , Levy Hadar , Finkel Orel , Eidler Pinhas , Ben-Horin Shomron , Eliakim Rami , Kopylov Uri
Published: May 2024

Background and Aims

Pan-enteric capsule endoscopy (PillCam Crohn’s capsule [PCC]) is a useful tool in diagnosing and monitoring Crohn’s disease [CD]. Eliakim score [ES] reliability and its strong correlation to Lewis score [LS] and to inflammatory biomarkers have been previously demonstrated using PCC in quiescent CD. We aimed to examine ES performance in active CD and its responsiveness to clinical/biochemical change over time.

Methods

Patients with CD who have started biologics were included, and were prospectively followed based on clinical visits, biomarkers, and PCC at baseline, after 14 and 52 weeks. Crohn’s disease activity index [CDAI], C-reactive protein [CRP], and faecal calprotectin [FC] levels were determined, and LS and ES were calculated [independently reviewed by two experienced readers]. Inter-class classification [ICC], Spearman’s baseline correlation, and repeated-measures correlation [RMC] analyses were performed.

Results

Seventy-four patients were included (age: 30.5 [range 23.3–45.0] years old, male 50%). In total, 142 PCCs were read [baseline, 62; week 14, 58; week 52, 22]. Inter-rater agreement was high for both LS and ES (ICC: 0.872 [p < 0.001] and 0.925 [<0.001], respectively). Baseline correlations between FC&ES [r = 0.509 [p < 0.001]) and FC&LS (r = 0.467 [p < 0.001]) were comparable [p = 0.56]. RMCs between the inflammatory biomarkers and ES were higher than between the former and LS (Reader 1: CRP r = 0.306 vs r = 0.138 [p = 0.057], FC r = 0.479 vs r = 0.297 [p = 0.034]; Reader 2 CRP r = 0.376 vs r = 0.204 [p = 0.035], FC r = 0.549 vs r = 0.412 [p = 0.075]). Moreover, ES was better correlated to CDAI than LS [p = 0.036].

Conclusions

ES is a reliable scoring system in assessing pan-enteric mucosal inflammation in active CD, and might have a better responsiveness to clinical/biochemical change over time compared to LS.
Mitral annular disjunction and its progression during childhood in Marfan syndrome
Authors: Doan Tam T , Iturralde Chavez Alejandra , Valdes Santiago O , Weigand Justin D , Wilkinson James C , Parthiban Anitha , Stephens Sara B , Pignatelli Ricardo H , Morris Shaine A
Published: May 2024

Aims

Data on mitral annular disjunction (MAD) in children with Marfan syndrome (MFS) are sparse. To investigate the diagnostic yield of MAD by echocardiography and cardiac magnetic resonance imaging (CMR), its prevalence and progression during childhood.

Methods and results

We included patients <21 years old with MFS, defined by 2010 Ghent criteria and a pathogenic FBN1 variant or ectopia lentis. Two readers measured systolic separation between the mitral valve (MV) posterior hinge point and left ventricular (LV) myocardium on initial and subsequent imaging. MAD was defined as MV-LV separation ≥2 mm, MV prolapse (MVP) as atrial displacement ≥2 mm. Kappa coefficients evaluated echocardiogram–CMR agreement. Bland–Altman and intraclass correlation coefficients (ICCs) assessed inter-rater and inter-modality reliability. Univariable mixed-effects linear regression was used to evaluate longitudinal changes of MAD. MAD was detected in 60% (110/185) eligible patients. MVP was present in 48% (53/110) of MAD and MAD in 90% (53/59) of MVP. MAD detection by CMR and echocardiography had 96% overall agreement (Kappa = 0.89, P < 0.001) and a 0.32 mm estimate bias (95% CI 0.00, 0.65). ICC by echocardiography, CMR, and between modalities were 0.97 (95% CI 0.93, 0.98), 0.92 (95% CI 0.79, 0.97), and 0.91 (95% CI 0.85, 0.94), respectively. MAD was associated with aortic root dilation (P < 0.001). MAD was found in children of all ages, increased +0.18 mm/year (95% CI +0.14, +0.22) during a median duration of 5.5 years (IQR 3.1, 7.5 years). MAD indexed by height yielded a constant value +0.0002 mm/m/year (95% CI −0.0002, +0.0005 mm/m/year).

Conclusion

MAD was common in pediatric MFS and was associated with aortic root dilation. MAD detection by echocardiography and CMR was highly reliable, suggesting that routine assessment in MFS is feasible. MAD was present in neonates and progressed over time but remained constant when indexing by height. Further studies are needed to evaluate MAD as a biomarker for clinical outcomes in pediatric MFS.
Psychometric validation of the short version of the Information Needs in Cardiac Rehabilitation scale through a first global assessment
Authors: Ghisi Gabriela Lima de Melo , da Cruz Mayara Moura Alves , Vanderlei Luiz Carlos Marques , Liu Xia , Xu Zhimin , Jiandani Mariya Prakash , Cuenza Lucky , Kouidi Evangelia , Giallauria Francesco , Mohammed Jibril , Maskhulia Lela , Trevizan Patricia Fernandes , Batalik Ladislav , Pereira Danielle Gomes , Tourkmani Nidal , Burazor Ivana , Venturini Elio , Lira Gerlene Grudka , Rehfeld Manuella Bennaton Cardoso Vieira , Neves Victor Ribeiro , Borges Geovana de Jesus , Kim Won-Seok , Cha Seungwoo , Zhang Ling , Grace Sherry L
Published: May 2024

Aims

Tailored education is recommended for cardiac patients, yet little is known about information needs in areas of the world where it is most needed. This study aims to assess (i) the measurement properties of the Information Needs in Cardiac Rehabilitation short version (INCR-S) scale and (ii) patient’s information needs globally.

Methods and results

In this cross-sectional study, English, simplified Chinese, Portuguese, or Korean versions of the INCR-S were administered to in- or out-patients via Qualtrics (January 2022–November 2023). Members of the International Council of Cardiovascular Prevention and Rehabilitation community facilitated recruitment. Importance and knowledge sufficiency of 36 items were rated. Links to evidence-based lay education were provided where warranted. A total of 1601 patients from 19 middle- and high-income countries across the world participated. Structural validity was supported upon factor analysis, with five subscales extracted: symptom response/medication, heart diseases/diagnostic tests/treatments, exercise and return-to-life roles/programmes to support, risk factors, and healthy eating/psychosocial management. Cronbach’s alpha was 0.97. Construct validity was supported through significantly higher knowledge sufficiency ratings for all items and information importance ratings for all subscales in cardiac rehabilitation (CR) enrolees vs. non-enrolees (all P < 0.001). All items were rated as very important—particularly regarding cardiac events, nutrition, exercise benefits, medications, symptom response, risk factor control, and CR—but more so in high-income countries in the Americas and Western Pacific. Knowledge sufficiency ranged from 30.0 to 67.4%, varying by region and income class. Ratings were highest for medications and lowest for support groups, resistance training, and alternative medicine.

Conclusion

Identification of information needs using the valid and reliable INCR-S can inform educational approaches to optimize patients’ health outcomes across the globe.
Modifiable risk factors and risk of myocardial infarction in offspring with parental disease
Authors: Møller Amalie Lykkemark , Larson Martin G , Xanthakis Vanessa , Vasan Ramachandran S , Andersson Charlotte
Published: May 2024

Aims

Children of patients with early-onset myocardial infarction (MI) are at increased risk, but the importance of concordant vs. discordant parent–offspring risk factor profiles on MI risk is largely unknown. We quantified the long-term absolute risk of MI according to shared risk factors in adulthood.

Methods and results

We sampled data on familial predisposed offspring and their parents from the Framingham Heart Study. Early MI was defined as a history of parental MI onset before age 55 in men or 65 in women. Individuals were matched 3:1 with non-predisposed offspring. Cardiovascular risk factors included obesity, smoking, hypertension, high cholesterol, and diabetes. We estimated the absolute 20-year incidence of MI using the Aalen–Johansen estimator. At age 40, the 20-year risk of MI varied by cholesterol level [high cholesterol 25.7% (95% confidence interval 11.2–40.2%) vs. non-high cholesterol 3.4% (0.5–6.4)] among predisposed individuals, and this difference was greater than in controls [high cholesterol 9.3% (1.5–17.0) vs. non-high cholesterol 2.5% (1.1–3.8)]. Similar results were observed for prevalent hypertension [26.7% (10.8–42.5) vs. 4.0% (0.9–7.1) in predisposed vs. 10.8% (3.2–18.3) and 2.1% (0.8–3.4) in controls]. Among offspring without risk factors, parental risk factors carried a residual impact on 20-year MI risk in offspring [0% (0–11.6) for 0–1 parental risk factors vs. 3.3% (0–9.8) for ≥2 parent risk factors at age 40, vs. 2.9% (0–8.4) and 8.5% (0–19.8) at age 50 years].

Conclusion

Children of patients with early-onset MI have low absolute risks of MI in the absence of midlife cardiovascular risk factors, especially if the parent also had a low risk factor burden prior to MI.
Sexually discordant selection is associated with trait-specific morphological changes and a complex genomic response
Authors: Audet Tyler , Krol Joelle , Pelletier Katie , Stewart Andrew D , Dworkin Ian
Published: May 2024

Sexes often have differing fitness optima, potentially generating intra-locus sexual conflict, as each sex bears a genetic “load” of alleles beneficial to the other sex. One strategy to evaluate conflict in the genome is to artificially select populations discordantly against established sexual dimorphism (SD), reintroducing attenuated conflict. We investigate a long-term artificial selection experiment reversing sexual size dimorphism in Drosophila melanogaster during ~350 generations of sexually discordant selection. We explore morphological and genomic changes to identify loci under selection between the sexes in discordantly and concordantly size-selected treatments. Despite substantial changes to overall size, concordant selection maintained ancestral SD. However, discordant selection altered size dimorphism in a trait-specific manner. We observe multiple possible soft selective sweeps in the genome, with size-related genes showing signs of selection. Patterns of genomic differentiation between the sexes within lineages identified potential sites maintained by sexual conflict. One discordant selected lineage shows a pattern of elevated genomic differentiation between males and females on chromosome 3L, consistent with the maintenance of sexual conflict. Our results suggest visible signs of conflict and differentially segregating alleles between the sexes due to discordant selection.
Allele frequency dynamics under sex-biased demography and sex-specific inheritance in a pedigreed jay population
Authors: Driscoll Rose M H , Beaudry Felix E G , Cosgrove Elissa J , Bowman Reed , Fitzpatrick John W , Schoech Stephan J , Chen Nancy
Published: May 2024

Sex-biased demography, including sex-biased survival or migration, can alter allele frequency changes across the genome. In particular, we can expect different patterns of genetic variation on autosomes and sex chromosomes due to sex-specific differences in life histories, as well as differences in effective population size, transmission modes, and the strength and mode of selection. Here, we demonstrate the role that sex differences in life history played in shaping short-term evolutionary dynamics across the genome. We used a 25-year pedigree and genomic dataset from a long-studied population of Florida Scrub-Jays (Aphelocoma coerulescens) to directly characterize the relative roles of sex-biased demography and inheritance in shaping genome-wide allele frequency trajectories. We used gene dropping simulations to estimate individual genetic contributions to future generations and to model drift and immigration on the known pedigree. We quantified differential expected genetic contributions of males and females over time, showing the impact of sex-biased dispersal in a monogamous system. Due to female-biased dispersal, more autosomal variation is introduced by female immigrants. However, due to male-biased transmission, more Z variation is introduced by male immigrants. Finally, we partitioned the proportion of variance in allele frequency change through time due to male and female contributions. Overall, most allele frequency change is due to variance in survival and births. Males and females make similar contributions to autosomal allele frequency change, but males make higher contributions to allele frequency change on the Z chromosome. Our work shows the importance of understanding sex-specific demographic processes in characterizing genome-wide allele frequency change in wild populations.
Australian Reconciliation and the Enduring Invisibility of Whiteness
Authors: Hand Samara
Published: May 2024

∞Reconciliation has emerged as one of the key goals of transitional justice and a favoured policy approach to address the racism, inequality and historical injustices experienced by Indigenous peoples in settler-colonial states. This article focuses on Australian reconciliation and argues that it has failed to critically engage with whiteness, limiting the potential of reconciliation to address the root causes of these issues. Drawing on critical whiteness studies and Aileen Moreton-Robinson’s concept of patriarchal white sovereignty, the article analyses the federal government’s push for constitutional recognition and demonstrates why reconciliation perpetuates the dispossession of Indigenous lands. The article also engages Michael Rothberg’s figure of the implicated subject to complicate the concept of whiteness and overcome the Indigenous/settler or victim/perpetrator binary. This article contributes to the field of transitional justice by advocating for a more explicit and critical examination of whiteness to advance justice in settler colonial contexts.
Neutrophil Extracellular Traps: An Emerging Therapeutic Target to Improve Infectious Disease Outcomes
Authors: Meier Angela , Sakoulas George , Nizet Victor , Ulloa Erlinda R
Published: May 2024

Neutrophils possess a diverse repertoire of pathogen clearance mechanisms, one of which is the formation of neutrophil extracellular traps (NETs). NETs are complexes of histone proteins and DNA coated with proteolytic enzymes that are released extracellularly to entrap pathogens and aid in their clearance, in a process known as NETosis. Intravascular NETosis may drive a massive inflammatory response that has been shown to contribute to morbidity and mortality in many infectious diseases, including malaria, dengue fever, influenza, bacterial sepsis, and severe acute respiratory syndrome coronavirus 2 infection. In this review we seek to (1) summarize the current understanding of NETs, (2) discuss infectious diseases in which NET formation contributes to morbidity and mortality, and (3) explore potential adjunctive therapeutics that may be considered for future study in treating severe infections driven by NET pathophysiology. This includes drugs specifically targeting NET inhibition and US Food and Drug Administration–approved drugs that may be repurposed as NET inhibitors.
Efficacy of a Novel Affitoxin Targeting Major Outer Membrane Protein Against Chlamydia trachomatis In Vitro and In Vivo
Authors: Li Mingyang , Yang Jia , Zhou Luqi , Zhang Jing , Li Yang , Chen Jun , Dong Haiyan , Zhang Lifang , Zhu Shanli
Published: May 2024

Targeted therapy is an attractive approach for treating infectious diseases. Affibody molecules have similar capability to antibodies that facilitate molecular recognition in both diagnostic and therapeutic applications. Targeting major outer membrane protein (MOMP) for treating infection of Chlamydia trachomatis, one of the most common sexually transmitted pathogens, is a promising therapeutic approach. Previously, we have reported a MOMP-specific affibody (ZMOMP:461) from phage display library. Here, we first fused it with modified Pseudomonas exotoxin (PE38KDEL) and a cell-penetrating peptide (CPP) to develop an affitoxin, Z461X-CPP. We then verified the addition of both toxin and CPPs that did not affect the affinitive capability of ZMOMP:461 to MOMP. Upon uptake by C trachomatis–infected cells, Z461X-CPP induced cell apoptosis in vitro. In an animal model, Z461X significantly shortened the duration of C trachomatis infection and prevented pathological damage in the mouse reproductive system. These findings provide compelling evidence that the MOMP-specific affitoxin has great potential for targeting therapy of C trachomatis infection.
Investigating drivers of telecare acceptance to improve healthcare quality for independently living older adults
Authors: Lassar Walfried , Hertelendy Attila J
Published: May 2024

Contemporary telecare systems facilitate the ability for older adults to age in place, keeping them out of residential care facilities and providing numerous quality-of-life advantages for both care receivers (CRs) and caregivers (CGs). However, despite the acceptance of digital health interventions among older adults and their CGs, telecare adoption has been slower than expected. This paper aimed to compare attitudes toward adopting telecare systems between CRs (aging adults) and their CGs (family/friends). Data were collected via an online survey. Respondents included aging adults concerned about their care (CRs) and older adults who cared for an aging loved one (CGs). Analysis of covariance and partial-least-squares techniques were used to examine the relationships between healthcare concerns for older adults, functional telecare benefits, and telecare acceptance. Concerns for healthcare status, mainly driven by CRs, positively impacted telecare acceptance. However, concerns for mental and physical stimulation had a negative relationship with telecare acceptance, while CGs showed a neutral relationship. Telecare’s ability to improve healthcare quality and cognitive stimulation positively impacted its acceptance. CGs mainly drove the impact of healthcare quality on telecare acceptance, while the relationship was not significant for CRs. CRs’ age reduced telecare acceptance, and higher educational levels of CGs increased telecare acceptance. We found significant differences in telecare acceptance and its drivers between CGs and CRs in the USA. In addition, we discerned that not all healthcare concerns or functional telecare characteristics influenced telecare acceptance equally between the two. Consequently, telecare providers must consider the different needs of constituencies interested in telecare to support the life quality of older adults.
Trading with Pariahs: North Korean Sanctions and the Challenge of Weaponized Interdependence
Authors: Preble Keith A , Willis Charmaine N
Published: May 2024

Why has North Korea avoided capitulating to economic sanctions pressures? We argue that economic sanctions have been ineffective and unsuccessful for three reasons: North Korea’s adeptness at evasion, other states’ unwillingness to enforce economic sanctions, and North Korea’s efforts to avoid panopticon effects via its diplomatic statecraft and policies that allow states to monitor and collect information on others. We contend that the implementation and enforcement of economic sanctions led North Korea to alter its trading network, reallocating trade to countries (or nodes) within its network willing to ignore international sanctions. As a result, these network shifts limited the ability of senders to weaponize the interdependence between them and North Korea effectively. We further highlight how North Korea conducts diplomatic statecraft in such a way that limits the impact of sanctions enforcing states from effectively monitoring it and limiting the impact of panopticon effects senders generate. To test our theory, we employ an ordinary least squares regression followed by social network analysis to understand how North Korea’s network of trade has adapted over time in the face of punishing economic sanctions. We find that states with greater diplomatic engagement enjoy better centrality than sanctions enforcing states. Also, economic sanctions at critical junctures induce changes to North Korea’s network over time with commercial imperatives to trade replaced by a North Korean near reliance on China. We further demonstrate that economic sanctions likely induce changes to the structure of the network as North Korea seeks to insulate itself from the impact of economic sanctions.
Machine learning and metagenomics identifies uncharacterized taxa inferred to drive biogeochemical cycles in a subtropical hypereutrophic estuary
Authors: Prabhu Apoorva , Tule Sanjana , Chuvochina Maria , Bodén Mikael , McIlroy Simon J , Zaugg Julian , Rinke Christian
Published: May 2024

Anthropogenic influences have drastically increased nutrient concentrations in many estuaries globally, and microbial communities have adapted to the resulting hypereutrophic ecosystems. However, our knowledge of the dominant microbial taxa and their potential functions in these ecosystems has remained sparse. Here, we study prokaryotic community dynamics in a temporal–spatial dataset, from a subtropical hypereutrophic estuary. Screening 54 water samples across brackish to marine sites revealed that nutrient concentrations and salinity best explained spatial community variations, whereas temperature and dissolved oxygen likely drive seasonal shifts. By combining short and long read sequencing data, we recovered 2,459 metagenome-assembled genomes, proposed new taxon names for previously uncharacterised lineages, and created an extensive, habitat specific genome reference database. Community profiling based on this genome reference database revealed a diverse prokaryotic community comprising 61 bacterial and 18 archaeal phyla, and resulted in an improved taxonomic resolution at lower ranks down to genus level. We found that the vast majority (61 out of 73) of abundant genera (>1% average) represented unnamed and novel lineages, and that all genera could be clearly separated into brackish and marine ecotypes with inferred habitat specific functions. Applying supervised machine learning and metabolic reconstruction, we identified several microbial indicator taxa responding directly or indirectly to elevated nitrate and total phosphorus concentrations. In conclusion, our analysis highlights the importance of improved taxonomic resolution, sheds light on the role of previously uncharacterised lineages in estuarine nutrient cycling, and identifies microbial indicators for nutrient levels crucial in estuary health assessments.
Microorganisms in subarctic soils are depleted of ribosomes under short-, medium-, and long-term warming
Authors: Söllinger Andrea , Ahlers Laureen S , Dahl Mathilde Borg , Sigurðsson Páll , Le Noir de Carlan Coline , Bhattarai Biplabi , Gall Christoph , Martin Victoria S , Rottensteiner Cornelia , Motleleng Liabo L , Breines Eva Marie , Verbruggen Erik , Ostonen Ivika , Sigurdsson Bjarni D , Richter Andreas , Tveit Alexander T
Published: May 2024

Physiological responses of soil microorganisms to global warming are important for soil ecosystem function and the terrestrial carbon cycle. Here, we investigate the effects of weeks, years, and decades of soil warming across seasons and time on the microbial protein biosynthesis machineries (i.e. ribosomes), the most abundant cellular macromolecular complexes, using RNA:DNA and RNA:MBC (microbial biomass carbon) ratios as proxies for cellular ribosome contents. We compared warmed soils and non-warmed controls of 15 replicated subarctic grassland and forest soil temperature gradients subject to natural geothermal warming. RNA:DNA ratios tended to be lower in the warmed soils during summer and autumn, independent of warming duration (6 weeks, 8–14 years, and > 50 years), warming intensity (+3°C, +6°C, and +9°C), and ecosystem type. With increasing temperatures, RNA:MBC ratios were also decreasing. Additionally, seasonal RNA:DNA ratios of the consecutively sampled forest showed the same temperature-driven pattern. This suggests that subarctic soil microorganisms are depleted of ribosomes under warm conditions and the lack of consistent relationships with other physicochemical parameters besides temperature further suggests temperature as key driver. Furthermore, in incubation experiments, we measured significantly higher CO2 emission rates per unit of RNA from short- and long-term warmed soils compared to non-warmed controls. In conclusion, ribosome reduction may represent a widespread microbial physiological response to warming that offers a selective advantage at higher temperatures, as energy and matter can be reallocated from ribosome synthesis to other processes including substrate uptake and turnover. This way, ribosome reduction could have a substantial effect on soil carbon dynamics.
Higher abundance of 2-dehydro-d-gluconate in the plasma of sub-fertile or infertile Bos taurus heifers
Authors: Marrella Mackenzie , Moorey Sarah E D , Campagna Shawn R , Sarumi Qudus , Biase Fernando H
Published: May 2024

Infertility or subfertility impacts approximately 5% and 15% of dairy and beef heifers (Bos taurus), respectively. Heifers that do not produce a calf within an optimum window of time have a significant negative impact on the profitability and sustainability of the cattle industry. Selection of heifers based on their fertility potential remains a challenge yet to be resolved. Here, we tested the hypothesis that heifers of different fertility potential have differing metabolome signatures in their plasma. We obtained blood from Bos taurus heifers at their first artificial insemination and processed the samples to separate the plasma. The heifers were classified based on their reproductive outcome as fertile (pregnant and delivered a calf after their first artificial insemination (AI)) or sub-fertile (Angus heifers: no pregnancy after two AI and exposure to a bull; Holstein heifers: no pregnancy by the third AI). We tested the relative abundance of 140 metabolites obtained from 22 heifers (Angus fertile n = 5, Angus sub-fertile n = 7, Holstein fertile N = 5, Holstein sub-fertile N = 5). The metabolite 2-Dehydro-D-gluconate (C6H10O7) was significantly more abundant in the plasma of sub-fertile heifers in both breeds (1.4-fold, false discovery rate < 0.1). In the context that a small proportion of circulating metabolites in the plasma were quantified in this study, the results show that the metabolomic profile in the blood stream may be associated with heifer fertility potential.